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佐藤康史

徳島大学

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2024年12月20日更新

職名: 特任教授
電話: 研究者総覧に該当データはありませんでした。
電子メール: sato.yasushi@tokushima-u.ac.jp
学歴: 1997/3: 医学博士
学位: 博士(医学)
職歴・経歴: 2016/12: 徳島大学特任講師, 病院 (-2017.2.)
2017/3: 徳島大学特任教授, 大学院医歯薬学研究部

専門分野・研究分野: 消化器内科学 (Gastroenterology)
消化器内視鏡
臨床腫瘍学

研究者総覧で最新データを確認する

2024年12月20日更新

専門分野・研究分野: 消化器内科学 (Gastroenterology)
消化器内視鏡
臨床腫瘍学
担当経験のある授業科目: 消化器コース (学部)
指導経験: 研究者総覧に該当データはありませんでした。

研究者総覧で最新データを確認する

2024年12月20日更新

専門分野・研究分野: 消化器内科学 (Gastroenterology)
消化器内視鏡
臨床腫瘍学

研究テーマ: 研究者総覧に該当データはありませんでした。

著書

佐藤康史 :
Pocket Drugs 2023,
2023年1月. 佐藤康史, 高山哲治 :
高齢者に対する癌治療.,
総合医学社, 2022年7月. 佐藤康史, 高山哲治 :
第1章総論 B. 難治がんとは 2. 早期診断・治療法の選択,
南江堂, 2021年7月. 佐藤康史, 高山哲治 :
癌性腹膜炎 / Carcinomatous peritonitis,
プレシジョン, 2019年. Tetsuji Takayama, Yasushi Sato and Naoki Muguruma :
Role of Alcohol and Metabolic Diseases in Colorectal Carcinogenesis.,
Springer-Verlag, Singapore, 2019. Yasushi Sato and Tetsuji Takayama :
Chapter 4. Upper Gastrointestinal Cancer Adjuvant Chemotherapy: Current Practices, Efficacy and Future Directions,
Nova Science Publishers, Sep. 2018. 佐藤康史 :
消化器癌薬物療法の進歩胃癌,
先端医療技術研究所, 2018年8月. 佐藤康史, 高山哲治 :
第4章消化器癌薬物療法の進歩胃癌,
先端医療技術研究所, 2018年8月. 根田寛, 越田吉一, 平山眞章, 佐藤康史, 松山友彦, 呂躍, 渡辺直樹, 新津洋司郎 :
トランスフェリンレセプターを介したヒト腫瘍細胞およびリンパ球への遺伝子導入の検討,
国際医書出版, 東京, 1995年.

論文

Tetsu Tomonari, Joji Tani, Yasushi Sato, Hironori Tanaka, Aasahiro Morishita, Koichi Okamoto, Yutaka Kawano, Masahiro Sogabe, Hiroshi Miyamoto and Tetsuji Takayama :
Initial treatment efficacy and safety of durvalumab plus tremelimumab combination therapy in unresectable hepatocellular carcinoma in clinical practice.,
JGH Open, Vol.8, No.10, e70033, 2024.

(要約): We aimed to evaluate the efficacy and safety of durvalumab plus tremelimumab (Dur + Tre) combination therapy in patients with unresectable hepatocellular carcinoma (uHCC) in clinical practice. We retrospectively evaluated 37 patients with uHCC from our institutions between April 2023 and January 2024. Patients were divided into first- and later-line groups for analysis of antitumor efficacy, adverse events (AEs), and transition rate to second-line treatment according to the Response Evaluation Criteria in Solid Tumors (RECIST). The disease control rate (DCR) for the first-line group was 80.9%, which was significantly higher than that for the later-line group (50%). The incidence of immune-related AEs (irAEs) was 24.3%, with grade 3 or higher irAEs including increased transaminase (8.1%), diarrhea (8.1%), and adrenal insufficiency (2.7%). The rates of drug withdrawal and discontinuation owing to AEs were 23.8% and 19%, respectively, in the first-line treatment and 31.2% and 12.5%, respectively, in the later-line treatment, with no significant difference. Analysis of changes in liver reserve using the albumin-bilirubin (ALBI) score showed no obvious loss of liver reserve for up to 12 weeks. The transition rate from first- to second-line therapy after progressive disease (PD) was as high as 94.7%. The efficacy and safety of Dur + Tre in clinical practice were comparable to those reported in a recent phase III trial. The first-line Dur + Tre therapy had a higher DCR than that of the later lines, and the transition rate to second-line therapy was considerably high, suggesting that Dur + Tre therapy would be more beneficial in first-line treatment.
(出版サイトへのリンク): ● Publication site (DOI): 10.1002/jgh3.70033
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 39371045; ● Search Scopus @ Elsevier (PMID): 39371045; ● Search Scopus @ Elsevier (DOI): 10.1002/jgh3.70033

(DOI: 10.1002/jgh3.70033, PubMed: 39371045) Kazuyoshi Noda, Yasushi Sato, Yasuyuki Okada, Kensei Nishida, Yutaka Kawano, Toshihito Tanahashi, Masahiro Bando, Koichi Okamoto, Masanori Takehara, Masahiro Sogabe, Hiroshi Miyamoto, Kei Daizumoto, Hiro-omi Kanayama and Tetsuji Takayama :
Exosomal miR-199a-3p Secreted From Cancer-Associated Adipocytes Promotes Pancreatic Cancer Progression.,
Cancer Medicine, Vol.13, No.20, e70265, 2024.

(要約): Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer. Recent studies indicated that cancer-associated adipocytes (CAAs) play crucial roles in tumor progression; however, the precise mechanism remains unknown. Here, we analyzed specific exosomal microRNAs (miRNA) signatures derived from pancreatic CAAs to investigate their role in cancer progression. CAAs were generated by co-culturing human adipocytes with human pancreatic cancer cells, and exosomes were isolated from the CAA-conditioned medium (CAA-CM). Small RNA-seq analysis was used to identify differentially expressed miRNAs in these exosomes. The effects of miRNAs on cell proliferation, migration/invasion, and drug sensitivity were examined. Luciferase reporter assays, real-time polymerase chain reaction, and western blotting were performed to investigate the molecular mechanisms of the miRNAs. The clinical relevance of the miRNAs was investigated using publicly available data and our cohort of patients with PDAC. miR-199a-3p expression was significantly increased in CAA-CM-derived exosomes. CAA-derived exosomes transferred miR-199a-3p to pancreatic cancer cells. Transfection with miR-199a-3p increased the proliferation, invasion, migration, and drug resistance of pancreatic cancer cells by downregulating SOCS7, increasing STAT3 phosphorylation, and upregulating SAA1 expression. High tissue miR-199a-3p expression is correlated with poor prognosis in patients with PDAC. Liquid biopsies revealed that exosomal miR-199a-3p could accurately differentiate patients with PDAC from healthy controls. Multivariate survival analysis indicated that miR-199a is an independent prognostic factor for PDAC. miR-199a-3p in CAA-derived exosomes contributes to the malignant transformation of pancreatic cancer via the SOCS7/STAT3/SAA1 pathway, suggesting its potential as a biomarker and therapeutic target for PDAC.
(キーワード): Humans / MicroRNAs / Exosomes / Pancreatic Neoplasms / Disease Progression / Cell Proliferation / Carcinoma, Pancreatic Ductal / Adipocytes / Cell Line, Tumor / Gene Expression Regulation, Neoplastic / Cell Movement / STAT3 Transcription Factor / Prognosis / Biomarkers, Tumor / Female / Male / Drug Resistance, Neoplasm
(出版サイトへのリンク): ● Publication site (DOI): 10.1002/cam4.70265
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 39431622; ● Search Scopus @ Elsevier (PMID): 39431622; ● Search Scopus @ Elsevier (DOI): 10.1002/cam4.70265

(DOI: 10.1002/cam4.70265, PubMed: 39431622) Masahiro Sogabe, Toshiya Okahisa, Miwako Kagawa, Takanori Kashihara, Shota Fujimoto, Tomoyuki Kawaguchi, Reiko Yokoyama, Kaizo Kagemoto, Hironori Tanaka, Yoshifumi Kida, Tetsu Tomonari, Yasushi Sato, Masahiko Nakasono and Tetsuji Takayama :
Metabolic dysfunction-associated steatotic liver disease and gallbladder polyp development: an observational study.,
Scientific Reports, Vol.14, No.1, 22446, 2024.

(要約): The influence of metabolic dysfunction-associated steatotic liver disease (MASLD) on gallbladder polyp development in both sexes remains elusive. Therefore, to clarify the role of MASLD in gallbladder polyp development, we investigated the longitudinal association between MASLD and gallbladder polyps. In this observational study, we included 5,527 gallbladder polyp-free patients who underwent > 2 health check-ups over > 2 years. Generalized estimation equations were used to analyze associations between MASLD and gallbladder polyp development according to repeated measures at baseline and the most recent stage. Gallbladder polyp development rates in men and women were 7.5% and 5.6% (p < 0.01), respectively. MASLD was not significantly correlated with gallbladder polyp development. Regarding the association between gallbladder polyp development (men: ≥6 mm and women: ≥5 mm) and the number of MASLD components following lifestyle habits, men and women with ≥ 4 MASLD components had odds ratios of 3.397 (95% confidence interval: 1.096-10.53) and 5.338 (1.054-27.04), respectively. Higher nonalcoholic fatty liver disease fibrosis scores were associated with significant risk of gallbladder polyp development in women (1.991, 1.047-3.785). Although MASLD influence on gallbladder polyp development differs by sex, close monitoring of patients with an increasing number of MASLD components is essential to prevent gallbladder polyp development. Specifically, men with ≥ 4 MASLD components should be monitored for gallbladder polyps measuring ≥ 6 mm.
(キーワード): Humans / Male / Female / Middle Aged / Polyps / Gallbladder Diseases / Adult / Risk Factors / Gallbladder / Non-alcoholic Fatty Liver Disease / Fatty Liver / Aged
(出版サイトへのリンク): ● Publication site (DOI): 10.1038/s41598-024-73429-1
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 39341964; ● Search Scopus @ Elsevier (PMID): 39341964; ● Search Scopus @ Elsevier (DOI): 10.1038/s41598-024-73429-1

(DOI: 10.1038/s41598-024-73429-1, PubMed: 39341964) Masahiro Sogabe, Toshiya Okahisa, Miwako Kagawa, Takanori Kashihara, Ryo Shinomiya, Takanori Miyake, Tomoyuki Kawaguchi, Reiko Yokoyama, Kaizo Kagemoto, Yoshifumi Kida, Yasuyuki Okada, Tetsu Tomonari, Yutaka Kawano, Yasushi Sato, Masahiko Nakasono and Tetsuji Takayama :
The association between alcohol consumption and cardiometabolic factors and liver fibrosis in metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction and alcohol-associated liver disease.,
Alimentary Pharmacology & Therapeutics, Vol.60, No.11-12, 1587-1598, 2024.

(要約): The relationships between alcohol consumption, cardiometabolic factors, and liver fibrosis in patients with metabolic dysfunction-associated steatotic liver disease and those with metabolic dysfunction and alcohol-associated liver disease remain unclear. To investigate the longitudinal associations among alcohol consumption, cardiometabolic factors, and liver fibrosis in patients with these two liver diseases. This observational cohort study included 1866 patients with metabolic dysfunction-associated steatotic liver disease and 521 patients with metabolic dysfunction and alcohol-associated liver disease who underwent > two health checkups over >2 years. The associations of both liver diseases with worsening non-invasive liver fibrosis scores were assessed using the Cox regression analysis. Both liver diseases independently worsened liver fibrosis in both sexes. However, the hazard ratio for worsening liver fibrosis in females was significantly higher with metabolic dysfunction and alcohol-associated liver disease than with metabolic dysfunction-associated steatotic liver disease. Worsening liver fibrosis was not associated with alcohol consumption. Among males with metabolic dysfunction-associated steatotic liver disease, the hazard ratio for worsening liver fibrosis was significantly higher in those with multiple cardiometabolic factors compared to those with a single cardiometabolic factor. Although both metabolic steatotic liver disease and metabolic alcohol-associated liver disease were correlated with liver fibrosis progression in both sexes, the impact of alcohol consumption and cardiometabolic factors on fibrosis progression differed by sex. Cardiometabolic factors may have a stronger impact on liver fibrosis than alcohol consumption in males with metabolic dysfunction-associated steatotic liver disease.
(キーワード): Humans / Male / Female / Middle Aged / Alcohol Drinking / Liver Cirrhosis / Adult / Cohort Studies / Aged / Liver Diseases, Alcoholic / Fatty Liver / Risk Factors / Sex Factors
(出版サイトへのリンク): ● Publication site (DOI): 10.1111/apt.18280
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 39310953; ● Search Scopus @ Elsevier (PMID): 39310953; ● Search Scopus @ Elsevier (DOI): 10.1111/apt.18280

(DOI: 10.1111/apt.18280, PubMed: 39310953) Masahiro Sogabe, Toshiya Okahisa, Miwako Kagawa, Motoko Sei, Hiroyuki Ueda, reiko yokoyama, Kaizo Kagemoto, Hironori Tanaka, Yoshifumi Kida, Fumika Nakamura, Tetsu Tomonari, Koichi Okamoto, Yutaka Kawano, Hiroshi Miyamoto, Yasushi Sato, Masahiko Nakasono and Tetsuji Takayama :
Association of metabolic dysfunction-associated steatotic liver disease with erosive esophagitis development: a longitudinal observational study.,
Journal of Gastroenterology and Hepatology, Vol.39, No.6, 1107-1114, 2024.

(要約): Although erosive esophagitis (EE) is associated with fatty liver and metabolic dysregulation, the association between EE and metabolic dysfunction-associated steatotic liver disease (MASLD) remains unclear. Thus, this study aimed to investigate the longitudinal association between MASLD and EE. We included 1578 patients without EE at baseline who underwent more than two health checkups over 2 years. Generalized estimation equations were used to analyze associations between MASLD and EE according to repeated measures at baseline and most recent stages. EE development rates in men and women were 14.5% and 7.2%, respectively. After adjusting for lifestyle habits, the odds ratios of MASLD for EE development in men and women were 1.907 (95% confidence interval [CI]: 1.289-2.832, P < 0.005) and 1.483 (95% CI: 0.783-2.811, P = 0.227), respectively. In the subgroup analysis, after adjusting for lifestyle habits, among men and women aged 50 years with more than three MASLD components, the odds ratios for EE development were 2.408 (95% CI: 1.505-3.855, P < 0.001) and 2.148 (95% CI: 1.093-4.221, P < 0.05), respectively. After adjusting for various factors, the significant risk factors for EE development were different between men and women. The influence of MASLD and other factors on EE development differed by sex and age. Particularly, patients aged 50 years with MASLD and with an increased number of MASLD components should be considered at increased risk for EE.
(出版サイトへのリンク): ● Publication site (DOI): 10.1111/jgh.16530
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 38419514; ● Search Scopus @ Elsevier (PMID): 38419514; ● Search Scopus @ Elsevier (DOI): 10.1111/jgh.16530

(DOI: 10.1111/jgh.16530, PubMed: 38419514) Masahiro Sogabe, Toshiya Okahisa, Miwako Kagawa, Motoko Sei, Hiroyuki Ueda, reiko yokoyama, Kaizo Kagemoto, Hironori Tanaka, Yoshifumi Kida, Fumika Nakamura, Tetsu Tomonari, Koichi Okamoto, Hiroshi Miyamoto, Yasushi Sato, Masahiko Nakasono and Tetsuji Takayama :
Association of variabilities in body mass index and waist circumference with newly achieved remission of metabolic dysfunction-associated fatty liver disease.,
Diabetes & Metabolic Syndrome, Vol.18, No.5, 103036, 2024.

(要約): Although body weight reduction is recommended to ameliorate nonalcoholic fatty liver disease, the effects of body mass index (BMI) and waist circumference (WC) variability on newly achieved remission of metabolic dysfunction-associated fatty liver disease (MAFLD) remain unclear. We aimed to investigate the longitudinal association between BMI and WC variabilities and newly achieved MAFLD remission in both sexes. Among 26,952 patients, 1823 with MAFLD diagnosed by ultrasonography and with >2 health checkups over >2 years from April 2014 to March 2021 were included in this observational cohort study. A generalized estimation equation model analyzed the association between BMI and WC and newly achieved MAFLD remission according to repeated measures at baseline and the most recent stage. Rates of MAFLD remission in male and female patients were 7.4 % and 6.0 %, respectively. Regarding decreased BMI variability, newly achieved MAFLD remission prevalence among the subgroups differed significantly between sexes (p < 0.001). In male patients, a decrease in BMI variability of ≥1.5 kg/m and WC variability of ≥4.2 cm had adjusted odds ratios (ORs) of 5.215 and 2.820, respectively, for newly achieved MAFLD remission. Among female patients, regular exercise and breakfast consumption were accelerating factors for newly achieved MAFLD remission. Non-invasive liver fibrosis scores significantly differed between MAFLD and newly achieved MAFLD remission, including in the subgroups (p < 0.01 and p < 0.001, respectively). Reducing BMI and WC variabilities in male patients and improving lifestyle habits in female patients may accelerate MAFLD remission.
(キーワード): Humans / Male / Female / Body Mass Index / Middle Aged / Non-alcoholic Fatty Liver Disease / Waist Circumference / Adult / Remission Induction / Follow-Up Studies / Prognosis / Metabolic Diseases
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.dsx.2024.103036
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 38754333; ● Search Scopus @ Elsevier (PMID): 38754333; ● Search Scopus @ Elsevier (DOI): 10.1016/j.dsx.2024.103036

(DOI: 10.1016/j.dsx.2024.103036, PubMed: 38754333) Koichi Okamoto, Tomoyuki Kawaguchi, Kaizo Kagemoto, Yoshifumi Kida, Yasuhiro Mitsui, Fumika Nakamura, Kouzou Yoshikawa, Masahiro Sogabe, Yasushi Sato, Joji Shunto, Yoshimi Bando, Mitsuo Shimada and Tetsuji Takayama :
Gastric fundic gland polyposis and cancer development after eradication of Helicobacter pylori in patient with gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS).,
Gastric Cancer, Vol.27, No.3, 635-640, 2024.

(要約): A 44-year-old woman with gastric cancer (GC) and fundic gland polyposis (FGPs) was referred to our hospital for further diagnosis and treatment. She successfully underwent eradication therapy for Helicobacter pylori (HP) 6 years ago, but did not exhibit FGPs at that time. When she underwent an esophagogastroduodenoscopy 2, 4, and 5 years after the eradication of HP, her imaging results revealed the existence of FGPs which gradually increased in her gastric fundus and body. Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) was suspected and a mutational analysis was performed, revealing an APC promoter 1B variant c.-191T > C. A robotic total gastrectomy with lymphadenectomy was performed. Histopathological analysis of the surgical specimens revealed GC with no lymph node metastasis. GAPPS is characterized by GC and FGPs. However, our case shows different gastric phenotypes that are dependent on the status of HP infection.
(キーワード): Female / Humans / Adult / Stomach Neoplasms / Helicobacter pylori / Adenocarcinoma / Helicobacter Infections / Polyps / Adenomatous Polyps
(出版サイトへのリンク): ● Publication site (DOI): 10.1007/s10120-024-01473-x
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 38407681; ● Search Scopus @ Elsevier (PMID): 38407681; ● Search Scopus @ Elsevier (DOI): 10.1007/s10120-024-01473-x

(DOI: 10.1007/s10120-024-01473-x, PubMed: 38407681) Masahiro Sogabe, Toshiya Okahisa, Miwako Kagawa, Takanori Kashihara, shota Fujimoto, Tomoyuki Kawaguchi, reiko yokoyama, Kaizo Kagemoto, Hironori Tanaka, Yoshifumi Kida, Tetsu Tomonari, Yutaka Kawano, Yasushi Sato, Masahiko Nakasono and Tetsuji Takayama :
Impact of alcohol consumption on metabolic dysfunction-associated fatty liver disease development and remission: A longitudinal cohort study.,
European Journal of Clinical Investigation, Vol.Online ahead of print., e14221, 2024.

(要約): The influence of alcohol intake on metabolic dysfunction-associated fatty liver disease (MAFLD) development and remission remains unclear; thus, we aimed to investigate their longitudinal associations. This observational cohort study included 6349 patients who underwent more than two health check-ups over >2 years between April 2013 and March 2021. Generalized estimation equations were used to analyse the longitudinal associations between changes in alcohol intake and MAFLD according to repeated measures at baseline and the most recent stage. The MAFLD development and remission rates were 20.4 and 5.1 and 9.1 and 4.7% in men and women, respectively. Although alcohol consumption was not a significant factor for MAFLD development, consuming 0.1-69.9 g/week (odds ratio [OR]: 0.672, 95% confidence interval [CI]: 0.469-0.964, p < .05) and ≥280 g/week were significant factors for MAFLD development in males (OR: 1.796, 95% CI: 1.009-3.196, p < .05) and females (OR: 16.74, 95% CI: 3.877-72.24, p < .001). Regardless of quantity and frequency, alcohol consumption was not a significant factor for MAFLD remission. Several noninvasive liver fibrosis scores were significantly associated with alcohol intake quantity and frequency in males with MAFLD development and remission (p < .05). The nonalcoholic fatty liver disease fibrosis score differed significantly between males with and without reduced alcohol intake (p < .05) who showed MAFLD remission. Although the influence of alcohol intake on MAFLD development and remission differed, alcohol consumption was not beneficial for MAFLD remission in either sex. Alcohol intake reduction or cessation is recommended to prevent liver fibrosis, even in those who achieve MAFLD remission.
(出版サイトへのリンク): ● Publication site (DOI): 10.1111/eci.14221
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 38634705; ● Search Scopus @ Elsevier (PMID): 38634705; ● Search Scopus @ Elsevier (DOI): 10.1111/eci.14221

(DOI: 10.1111/eci.14221, PubMed: 38634705) Masahiro Sogabe, Toshiya Okahisa, Miwako Kagawa, Motoko Sei, Kaizo Kagemoto, Hironori Tanaka, Yoshifumi Kida, Fumika Nakamura, Tetsu Tomonari, Koichi Okamoto, Hiroshi Miyamoto, Yasushi Sato, Masahiko Nakasono and Tetsuji Takayama :
Association of metabolic dysfunction-associated fatty liver disease with gallstone development: A longitudinal study.,
Journal of Gastroenterology and Hepatology, Vol.39, No.4, 754-761, 2024.

(要約): The influence of metabolic dysfunction-associated fatty liver disease on gallstone development remains unclear. We aimed to investigate the longitudinal association between metabolic dysfunction-associated fatty liver disease and gallstone development in both men and women. This observational cohort study included 5398 patients without gallstones who underwent > 2 health check-ups between April 1, 2014, and March 31, 2020. A generalized estimation equation model was used to analyze the association between metabolic dysfunction-associated fatty liver disease and gallstone development according to repeated measures at baseline and most recent stage. After adjustment, the odds ratios of metabolic dysfunction-associated fatty liver disease for gallstone development in men and women were 3.019 (95% confidence interval [CI]: 1.901-4.794) and 2.201 (95% CI: 1.321-3.667), respectively. Among patients aged 50 years, the odds ratio for gallstone development was significantly enhanced with increasing metabolic dysfunction-associated fatty liver disease component numbers in both sexes; however, no significance was observed in those aged < 50 years. Other significant risk factors for gallstone development were age (odds ratio: 1.093, 95% CI: 1.060-1.126) and waist circumference (odds ratio: 1.048, 95% CI: 1.018-1.079) in men and age (odds ratio: 1.035, 95% CI: 1.003-1.067) and current smoking (odd ratio: 5.465, 95% CI: 1.881-15.88) in women. Although the risk factors for gallstone development differed between sexes, metabolic dysfunction-associated fatty liver disease was common. Paying attention to an increase in the number of metabolic dysfunction-associated fatty liver disease components in patients aged 50 years is important for gallstone prevention.
(出版サイトへのリンク): ● Publication site (DOI): 10.1111/jgh.16483
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 38212880; ● Search Scopus @ Elsevier (PMID): 38212880; ● Search Scopus @ Elsevier (DOI): 10.1111/jgh.16483

(DOI: 10.1111/jgh.16483, PubMed: 38212880) Ryo Shinomiya, Yasushi Sato, Takanori Yoshimoto, Tomoyuki Kawaguchi, Akihiro Hirao, Koichi Okamoto, Yutaka Kawano, Masahiro Sogabe, Hiroshi Miyamoto and Tetsuji Takayama :
A case of treatmentresistant advanced gastric cancer with FGFR2gene alteration successfully treated with pemigatinib.,
International Cancer Conference Journal, Vol.13, 240-244, 2024.

(出版サイトへのリンク): ● Publication site (DOI): 10.1007/s13691-024-00669-3
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1007/s13691-024-00669-3

(DOI: 10.1007/s13691-024-00669-3) Akinari Kasai, Jinsei Miyoshi, Yasushi Sato, Koichi Okamoto, Hiroshi Miyamoto, Takashi Kawanaka, Chisato Tonoiso, Masafumi Harada, Masakazu Goto, Takahiro Yoshida, Akihiro Haga and Tetsuji Takayama :
A novel CT-based radiomics model for predicting response and prognosis of chemoradiotherapy in esophageal squamous cell carcinoma.,
Scientific Reports, Vol.14, No.1, 2039, 2024.

(要約): No clinically relevant biomarker has been identified for predicting the response of esophageal squamous cell carcinoma (ESCC) to chemoradiotherapy (CRT). Herein, we established a CT-based radiomics model with artificial intelligence (AI) to predict the response and prognosis of CRT in ESCC. A total of 44 ESCC patients (stage I-IV) were enrolled in this study; training (n = 27) and validation (n = 17) cohorts. First, we extracted a total of 476 radiomics features from three-dimensional CT images of cancer lesions in training cohort, selected 110 features associated with the CRT response by ROC analysis (AUC ≥ 0.7) and identified 12 independent features, excluding correlated features by Pearson's correlation analysis (r ≥ 0.7). Based on the 12 features, we constructed 5 prediction models of different machine learning algorithms (Random Forest (RF), Ridge Regression, Naive Bayes, Support Vector Machine, and Artificial Neural Network models). Among those, the RF model showed the highest AUC in the training cohort (0.99 [95%CI 0.86-1.00]) as well as in the validation cohort (0.92 [95%CI 0.71-0.99]) to predict the CRT response. Additionally, Kaplan-Meyer analysis of the validation cohort and all the patient data showed significantly longer progression-free and overall survival in the high-prediction score group compared with the low-prediction score group in the RF model. Univariate and multivariate analyses revealed that the radiomics prediction score and lymph node metastasis were independent prognostic biomarkers for CRT of ESCC. In conclusion, we have developed a CT-based radiomics model using AI, which may have the potential to predict the CRT response as well as the prognosis for ESCC patients with non-invasiveness and cost-effectiveness.
(キーワード): Humans / Esophageal Squamous Cell Carcinoma / Artificial Intelligence / Bayes Theorem / Esophageal Neoplasms / Radiomics / Prognosis / Chemoradiotherapy / Tomography, X-Ray Computed
(徳島大学機関リポジトリ): ● Metadata: 119113
(出版サイトへのリンク): ● Publication site (DOI): 10.1038/s41598-024-52418-4
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 38263395; ● Search Scopus @ Elsevier (PMID): 38263395; ● Search Scopus @ Elsevier (DOI): 10.1038/s41598-024-52418-4

(徳島大学機関リポジトリ: 119113, DOI: 10.1038/s41598-024-52418-4, PubMed: 38263395) Yutaka Kawano, Maki Tanaka, Yasushi Sato, Shigekazu Sugino, Jun Suzuki, Masaki Fujishima, Eri Okumura, Hideo Takekoshi, Osamu Uehara, Shintaro Sugita, Yoshihiro Abiko, Tetsu Tomonari, Hironori Tanaka, Hidekatsu Takeda and Tetsuji Takayama :
Acanthopanax senticosus ameliorates steatohepatitis through HNF4 alpha pathway activation in mice.,
Scientific Reports, Vol.14, No.1, 110, 2024.

(要約): Non-alcoholic fatty liver disease is a common liver disease worldwide, and is associated with dysregulation of lipid metabolism, leading to inflammation and fibrosis. Acanthopanax senticosus Harms (ASH) is widely used in traditional medicine as an adaptogen food. We examined the effect of ASH on steatohepatitis using a high-fat diet mouse model. Mice were fed a choline-deficient, L-amino acid-defined, high-fat diet with ASH extract (ASHE). After 6 weeks, liver RNA transcriptome sequencing (RNA-Seq) was performed, followed by Ingenuity Pathway Analysis (IPA). Our findings revealed that mice fed a high-fat diet with 5% ASHE exhibited significantly reduced liver steatosis. These mice also demonstrated alleviated inflammation and reduced fibrosis in the liver. IPA of RNA-Seq indicated that hepatocyte nuclear factor 4 alpha (HNF4 alpha), a transcription factor, was the activated upstream regulator (P-value 0.00155, z score = 2.413) in the liver of ASHE-fed mice. Adenosine triphosphate binding cassette transporter 8 and carboxylesterase 2, downstream targets of HNF4 alpha pathway, were upregulated. Finally, ASHE-treated HepG2 cells exposed to palmitate exhibited significantly decreased lipid droplet contents. Our study provides that ASHE can activate HNF4 alpha pathway and promote fat secretion from hepatocytes, thereby serving as a prophylactic treatment for steatohepatitis in mice.
(キーワード): Animals / Mice / Hepatocyte Nuclear Factor 4 / Eleutherococcus / Liver / Non-alcoholic Fatty Liver Disease / Inflammation / Disease Models, Animal / Fibrosis / Mice, Inbred C57BL / Diet, High-Fat
(徳島大学機関リポジトリ): ● Metadata: 119444
(出版サイトへのリンク): ● Publication site (DOI): 10.1038/s41598-023-50625-z
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 38167633; ● Search Scopus @ Elsevier (PMID): 38167633; ● Search Scopus @ Elsevier (DOI): 10.1038/s41598-023-50625-z

(徳島大学機関リポジトリ: 119444, DOI: 10.1038/s41598-023-50625-z, PubMed: 38167633) Nobuko Nakamura, Shinji Hasebe, Shintaro Yamanaka, Tomomi Fujii, Taketsugu Fujibuchi, Teruki Kitani, Kazuto Takeuchi, Yasushi Sato, Yoshitaro Shindo, Toshifumi Ozaki, Toshihiro Nishisho, Masahiro Tabata and Yoshihiro Yakushijin :
Treatments and prognostic factors for bone and soft tissue sarcoma in non-urban areas in Japan.,
International Journal of Clinical Oncology, Vol.Epub ahead of print, 2023.

(要約): Although bone and soft tissue sarcoma is recognized as a rare cancer that originates throughout the body, few comprehensive reports regarding it have been published in Japan. Bone and soft tissue sarcomas were tabulated from the Cancer Registries at eight university hospitals in the Chugoku-Shikoku region. Prognostic factors in cases were extracted in a single facility and have been analyzed. From 2016 to 2019, 3.4 patients with bone and soft tissue sarcomas per a general population of 100,000 were treated at eight university hospitals. The number of patients who underwent multidisciplinary treatment involving collaboration among multiple clinical departments has been increasing recently. In the analysis carried out at a single institute (Ehime University Hospital), a total of 127 patients (male/female: 54/73) with an average age of 67.0 y (median 69.5) were treated for four years, with a 5-year survival rate of 55.0%. In the analysis of prognostic factors by multivariate, disease stage and its relative treatment, renal function (creatinine), and a patient's ability of self-judgment, and a patient's mobility and physical capability were associated with patient prognosis regarding bone and soft tissue sarcomas. Interestingly, age did not affect the patient's prognosis (> 70 vs ≦ 70). Physical and social factors may affect the prognosis of patients with bone and soft tissue sarcomas, especially those living in non-urban areas.
(出版サイトへのリンク): ● Publication site (DOI): 10.1007/s10147-023-02453-4
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 38155238; ● Search Scopus @ Elsevier (PMID): 38155238; ● Search Scopus @ Elsevier (DOI): 10.1007/s10147-023-02453-4

(DOI: 10.1007/s10147-023-02453-4, PubMed: 38155238) Tetsu Tomonari, Joji Tani, Yasushi Sato, Hironori Tanaka, Takahiro Tanaka, Tatsuya Taniguchi, Yutaka Kawano, Asahiro Morishita, Koichi Okamoto, Masahiro Sogabe, Hiroshi Miyamoto, Tsutomu Masaki and Tetsuji Takayama :
Clinical Features and Outcomes of Conversion Therapy in Patients with Unresectable Hepatocellular Carcinoma.,
Cancers, Vol.15, No.21, 5221, 2023.

(要約): <jats:p>This retrospective multicenter study analyzed 244 patients with unresectable hepatocellular carcinoma treated with lenvatinib (LEN) and atezolizumab + bevacizumab (Atezo + Bev) to examine the characteristics, treatment courses, and prognoses. The cases of patients who could achieve HCC downstaging from Barcelona Clinic Liver Cancer (BCLC) stage B or C to A or zero indicated the need for conversion therapy. The patients' prognoses with and without conversion therapy were compared. Of the 244 patients, 12 (4.9%) underwent conversion therapy, six out of 131 (4.6%) were treated with LEN, and six out of 113 (5.3%) were treated with Atezo + Bev. Eleven patients (91.7%) with a modified albumin bilirubin (mALBI) grade 1 or 2a and BCLC-B stage showed significantly higher rates of transition during conversion therapy (p < 0.05). The patients undergoing conversion therapy had a significantly longer median overall survival rate than those receiving chemotherapy alone (1208 [1064–NA] vs. 569 [466–704] days, p < 0.01). A comparison of the patients who achieved a partial response with and without conversion was evaluated using propensity score matching to reduce the confounding factors, showing a significant survival benefit in the conversion group (1208 [1064–NA] vs. 665 days, p < 0.01). Among the patients with u-HCC who were treated with LEN and Atezo + Bev, those with mALBI 1 + 2a and BCLC-B were likely to achieve conversion therapy with downstaging.</jats:p>
(出版サイトへのリンク): ● Publication site (DOI): 10.3390/cancers15215221
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1360580235903920000; ● Summary page in Scopus @ Elsevier: 2-s2.0-85176601973

(DOI: 10.3390/cancers15215221, CiNii: 1360580235903920000, Elsevier: Scopus) Reiko Yokoyama, Yasushi Sato, Fumika Nakamura, Kaizo Kagemoto, Yasuhiro Mitsui, Koichi Okamoto, Yutaka Kawano, Masahiro Sogabe, Hiroshi Miyamoto and Tetsuji Takayama :
Efficacy of immune checkpoint inhibitors in patients with anorectal melanoma in association with immune-related adverse events: a case series.,
Clinical Journal of Gastroenterology, Vol.Online ahead of print., 2023.

(要約): Anorectal melanoma (AM) is a rare subtype of mucosal melanoma with a poor prognosis. Given its rarity compared to its cutaneous counterpart, the benefits and side effects of immune checkpoint inhibitor (ICI) therapy and the relationship between side effects and prognosis remain unclear. Herein, we describe the clinical presentation of five patients with AM treated with ICI as well as their relationship to the treatment course and the development of immune-related adverse events (irAEs). Three patients received sequential or concurrent administrations of nivolumab and ipilimumab, one received nivolumab alone, and one received ipilimumab alone. The response rate (RR) and disease control rate (DCR) were 40% and 80%, respectively. Pituitary and hepatic dysfunctions were the most common irAEs observed (40% each), followed by thyroid, diarrhea, and renal dysfunctions (20% each). The RR was 67% in patients with irAEs while no response was observed in patients without irAEs. DCR was 100% and 50% in patients with and without irAEs, respectively. Overall survival was 34 months in irAE and 8.75 months in non-irAE cases, with a longer survival trend in irAE cases. ICI therapy was effective and well-tolerated by AM patients, with potentially better outcomes for those who experienced irAEs compared to those who did not.
(出版サイトへのリンク): ● Publication site (DOI): 10.1007/s12328-023-01849-z
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 37632658; ● Summary page in Scopus @ Elsevier: 2-s2.0-85169147432

(DOI: 10.1007/s12328-023-01849-z, PubMed: 37632658, Elsevier: Scopus) Koichi Okamoto, Tomoyuki Kawaguchi, Kaizo Kagemoto, Yoshifumi Kida, Yasuhiro Mitsui, Yasushi Sato and Tetsuji Takayama :
"Tip-in underwater endoscopic mucosal resection" without submucosal injection for superficial nonampullary duodenal adenomas.,
Endoscopy, Vol.55, No.S1, E965-E966, 2023.

(キーワード): Humans / Endoscopic Mucosal Resection / Duodenal Neoplasms / Duodenum / Injections
(徳島大学機関リポジトリ): ● Metadata: 118931
(出版サイトへのリンク): ● Publication site (DOI): 10.1055/a-2134-9080
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 37604451; ● Summary page in Scopus @ Elsevier: 2-s2.0-85168452995

(徳島大学機関リポジトリ: 118931, DOI: 10.1055/a-2134-9080, PubMed: 37604451, Elsevier: Scopus) Taku Takahashi, Yasushi Sato, Takanori Kashihara, Yoshihiro Miyata, Yasuteru Fujino, Yasuhiro Mitsui, Koichi Okamoto, Hiroshi Miyamoto, Yasuhiko Nishioka and Tetsuji Takayama :
Nintedanib-Induced Gastric Antral Vascular Ectasia in Patients with Idiopathic Pulmonary Fibrosis.,
ACG Case Reports Journal, Vol.10, e01107, 2023.

(出版サイトへのリンク): ● Publication site (DOI): 10.14309/crj.0000000000001107
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.14309/crj.0000000000001107

(DOI: 10.14309/crj.0000000000001107) Yasushi Sato, Koichi Okamoto, Yutaka Kawano, Akinari kasai, Tomoyuki Kawaguchi, Tamotsu Sagawa, Masahiro Sogabe, Hiroshi Miyamoto and Tetsuji Takayama :
Novel Biomarkers of Gastric Cancer: Current Research and Future Perspectives.,
Journal of Clinical Medicine, Vol.12, 4646, 2023.

(出版サイトへのリンク): ● Publication site (DOI): 10.3390/jcm12144646
(文献検索サイトへのリンク): ● Summary page in Scopus @ Elsevier: 2-s2.0-85166316472

(DOI: 10.3390/jcm12144646, Elsevier: Scopus) Tamotsu Sagawa, Yasushi Sato, Hiroyuki Nagashimia, Kohichi Takada, Mamoru Takahashi, Masahiro Hiarakawa, Kyoko Hamaguchi, Fumito Tamura, Koshi Fujikawa, Koichi Okamoto, Yutaka Kawano, Masahiro Sogabe, Hiroshi Miyamoto and Tetsuji Takayama :
Hilar/mediastinal and cutaneous drug-induced sarcoidosis-like reaction associated with immune checkpoint inhibitors in metastatic colorectal cancer: a case report.,
Frontiers in Immunology, Vol.14, 1203621, 2023.

(要約): Immune checkpoint inhibitors (ICIs) are the standard treatment for metastatic colorectal cancer (mCRC) with high microsatellite instability (MSI-H). Among immune-related adverse events (irAEs), drug-induced sarcoidosis-like reactions (DISR) are often difficult to differentiate from cancer progression. This is a case of a woman in her mid-60s, with mCRC (RAS wild/BRAF mutant/MSI-H) and abdominal lymph node metastasis, treated with four courses of ipilimumab + nivolumab every 3 weeks, followed by nivolumab every 2 weeks as third-line treatment. After treatment, the original lymph node metastases shrank, but hilar/mediastinal lymph nodes appeared. Endoscopic ultrasound-guided fine-needle aspiration of these lymph nodes revealed multiple epithelioid granulomas without necrosis, indicating a sarcoidosis-like reaction. Fluorodeoxyglucose-positron emission tomography scan showed abnormal subcutaneous accumulation in bilateral forearms and bilateral knee joints. Biopsy of the cutaneous lesions was also performed, which revealed epithelioid granulomas. As the patient had no symptoms in other organs, no specific therapeutic intervention was administered. After the discontinuation of immunotherapy, the sarcoidosis-like reaction regressed without cancer relapse. Clinicians should be aware of the possibility of DISR as an irAE during the ICI treatment of mCRC. In suspected cases of DISR following ICI therapy, it is important to differentiate between cancer progression and DISR through histological diagnosis for the subsequent strategy, as radiological and serological findings are not definitive.
(キーワード): Humans / Female / Nivolumab / Immune Checkpoint Inhibitors / Neoplasm Recurrence, Local / Sarcoidosis / Colonic Neoplasms / Rectal Neoplasms / Granuloma / Lymphatic Metastasis
(出版サイトへのリンク): ● Publication site (DOI): 10.3389/fimmu.2023.1203621
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 37492584; ● Summary page in Scopus @ Elsevier: 2-s2.0-85165588753

(DOI: 10.3389/fimmu.2023.1203621, PubMed: 37492584, Elsevier: Scopus) Tamotsu Sagawa, Yasushi Sato, Masahiro Hirakawa, Kyoko Hamguchi, Fumito Tamura, Hiroyuki Nagashima, Koshi Fujikawa, Koichi Okamoto, Yutaka Kawano, Masahiro Sogabe, Hiroshi Miyamoto and Tetsuji Takayama :
Case Report: Longitudinal monitoring of clonal evolution by circulating tumor DNA for resistance to anti-EGFR antibody in a case of metastatic colorectal cancer.,
Frontiers in Oncology, Vol.13, 1203296, 2023.

(要約): Treatment with anti-EGFR antibody has been shown to prolong survival in patients with RAS wild-type metastatic colorectal cancer (mCRC). However, even patients who initially respond to anti-EGFR antibody therapy, almost without exception, develop resistance to the therapy and then fail to respond. Secondary mutations in the mitogen-activated protein (MAPK) signaling pathway (mainly in NRAS and BRAF) have been implicated in anti-EGFR resistance. However, the process by which resistant clones develop during therapy has not been elucidated, and considerable intrapatient and interpatient heterogeneity exists. Circulating tumor DNA (ctDNA) testing has recently allowed the noninvasive detection of heterogeneous molecular alterations that underlie the evolution of resistance to anti-EGFR. In this report, we describe our observation of genomic alterations in and in a patient with acquired resistance to anti-EGFR antibody drugs by tracking clonal evolution using serial ctDNA anaylsis. A 54-year-old woman was initially diagnosed with sigmoid colon cancer with multiple liver metastases. After receiving first-line mFOLFOX + cetuximab, second-line FOLFIRI + ramucirumab, third-line trifluridine/tipiracil + bevacizumab, fourth-line regorafenib, and fifth-line CAPOX + bevacizumab, she was rechallenged with CPT-11 + cetuximab. The best response to anti-EGFR rechallenge therapy was a partial response. in the ctDNA was assessed during treatment. The status changed from wild type to mutant type, back to wild type, and again to mutant type ( codon 61) during the course of treatment. In this report, tracking of ctDNA allowed us to describe clonal evolution in a case in which we observed genomic alterations in and in a patient who acquired resistance to anti-EGFR antibody drugs during treatment. It is reasonable to consider repeat molecular interrogation during progression in patients with mCRC by using ctDNA analysis, which could help to identify patients who may benefit from a rechallenge strategy.
(出版サイトへのリンク): ● Publication site (DOI): 10.3389/fonc.2023.1203296
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 37434969; ● Summary page in Scopus @ Elsevier: 2-s2.0-85164679900

(DOI: 10.3389/fonc.2023.1203296, PubMed: 37434969, Elsevier: Scopus) Takayuki Matsumoto, Junji Umeno, Keisuke Jimbo, Masami Arai, Itaru Iwama, Hiroshi Kashida, Takahiro Kudo, Koichi Koizumi, Yasushi Sato, Shigeki Sekine, Shinji Tanaka, Kohji Tanakaya, Kazuo Tamura, Keiji Hirata, Suguru Fukahori, Motohiro Esaki, Hideki Ishikawa, Takeo Iwama, Yasushi Okazaki, Yutaka Saito, Nariaki Matsuura, Michihiro Mutoh, Naohiro Tomita, Takashi Akiyama, Toshiki Yamamoto, Hideyuki Ishida and Yoshiko Nakayama :
Clinical Guidelines for Diagnosis and Management of Juvenile Polyposis Syndrome in Children and Adults-Secondary Publication.,
Journal of the Anus, Rectum and Colon, Vol.7, No.2, 115-125, 2023.

(要約): are also associated with hereditary hemorrhagic telangiectasia-JPS complex, inducing regular cardiovascular survey. Despite growing concerns regarding the managing JPS in Japan, there are no practical guidelines. To address this situation, the guideline committee was organized by the Research Group on Rare and Intractable Diseases granted by the Ministry of Health, Labor and Welfare involving specialists from multiple academic societies. The present clinical guidelines explain the principles in the diagnosis and management of JPS with three clinical questions and corresponding recommendations based on a careful review of the evidence and involve incorporating the concept of the Grading of Recommendations, Assessment, Development, and Evaluation system. Herein, we present the clinical practice guidelines of JPS to promote seamless implementation of accurate diagnosis and appropriate management of pediatric, adolescent, and adult patients with JPS.
(出版サイトへのリンク): ● Publication site (DOI): 10.23922/jarc.2023-002
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 37113581; ● Search Scopus @ Elsevier (PMID): 37113581; ● Search Scopus @ Elsevier (DOI): 10.23922/jarc.2023-002

(DOI: 10.23922/jarc.2023-002, PubMed: 37113581) Masahiro Sogabe, Toshiya Okahisa, Miwako Kagawa, Hiroyuki Ueda, Kaizo Kagemoto, Hironori Tanaka, Yoshifumi Kida, Tetsu Tomonari, Tatsuya Taniguchi, Koichi Okamoto, Hiroshi Miyamoto, Yasushi Sato, Masahiko Nakasono and Tetsuji Takayama :
Influence of alcohol on newly developed metabolic dysfunction-associated fatty liver disease in both sexes: A longitudinal study.,
Clinical Nutrition, Vol.42, No.5, 810-816, 2023.

(要約): The influence of changes in alcohol consumption on newly developed metabolic dysfunction-associated fatty liver disease (MAFLD) is unclear. We investigated the influence of alcohol consumption on newly developed MAFLD in both sexes. This observational cohort study included 4071 patients who underwent more than two health check-ups between 2015 and 2020 over an interval of more than a year. Generalised estimating equations were used for analyses. At baseline, the rates of drinking and MAFLD between men and women were 72.5% versus 41.7% and 42.2% versus 22.1%, respectively. At the most recent stage, the rates of an increase in alcohol consumption for men and women were 13.3% and 8.7%, respectively, and 311/1192 (26.1%) men and 155/1566 (9.9%) women had newly developed MAFLD. The odds ratio (OR) for drinking in patients with newly developed MAFLD was 0.863 (men) (95% confidence interval [CI], 0.676-1.102, p = 0.237) and 1.041 (women) (95% CI, 0.753-1.439, p = 0.808); the OR for women who drank 140-279.9 g/week was 2.135 (95% CI, 1.158-3.939, p < 0.05) and that for all drinking categories among women was >1. Several non-invasive fibrosis scores were significantly associated with the quantity of alcohol consumption in patients with newly developed MAFLD (p < 0.005). Alcohol consumption had no significant protective effect against newly developed MAFLD in both sexes, regardless of quantity. Conversely, alcohol consumption ≥140 g/week was a risk factor for newly developed MAFLD in women. The development of liver fibrosis with increased alcohol intake should be considered in patients with MAFLD.
(徳島大学機関リポジトリ): ● Metadata: 118599
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.clnu.2023.03.020
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 37043935; ● Search Scopus @ Elsevier (PMID): 37043935; ● Search Scopus @ Elsevier (DOI): 10.1016/j.clnu.2023.03.020

(徳島大学機関リポジトリ: 118599, DOI: 10.1016/j.clnu.2023.03.020, PubMed: 37043935) Tetsu Tomonari, Hironori Tanaka, Takahiro Tanaka, Tatsuya Taniguchi, Masahiro Sogabe, Yutaka Kawano, Koichi Okamoto, Hiroshi Miyamoto, Yasushi Sato and Tetsuji Takayama :
A case of complete response with rechallenge-lenvatinib plus transcatheter arterial chemoembolization for unresectable hepatocellular carcinoma refractory to multiple molecular-targeted agent treatments.,
Clinical Journal of Gastroenterology, Vol.16, No.3, 438-443, 2023.

(要約): The efficacy of lenvatinib (LEN) plus transcatheter arterial chemoembolization (LEN-TACE) has been reported, but its effect on unresectable hepatocellular carcinoma (HCC) refractory to LEN therapy has not been demonstrated. We report a case of HCC refractory to multiple molecular-targeted agents (MTA) treatments, including LEN, that was successfully treated with LEN-TACE. A 59-year-old man was referred to our department with multiple HCCs and a background of hepatitis B virus infection. TACE was the initial treatment. However, he was determined to be TACE-refractory, and multitargeted therapy was initiated. LEN was started at 12 mg/day but resulted in progressive disease (PD) after 13 months of the administration. The response to second-line sorafenib was PD after 2 months. Third-line therapy with atezolizumab + bevacizumab was stopped after one course because of an immune-related adverse event (i.e., dermatitis). The response to fourth-line regorafenib was PD at 2 months, and the response to fifth-line cabozantinib was PD after 6 months. The efficacy of LEN-TACE was recently reported; therefore, we decided to attempt LEN-TACE therapy as a salvage line. After obtaining the patient's consent to repeat LEN and TACE, treatment was initiated. The tumor markers levels markedly reduced after LEN-TACE therapy. After three additional TACE treatments with continued LEN administration, the tumor marker levels normalized, and complete response was determined based on RECIST guidelines. LEN-TACE therapy may effectively treat unresectable advanced HCC in the LEN-rechallenge setting and may be a treatment option as a last-line therapeutic option.
(出版サイトへのリンク): ● Publication site (DOI): 10.1007/s12328-023-01777-y
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36856957; ● Search Scopus @ Elsevier (PMID): 36856957; ● Search Scopus @ Elsevier (DOI): 10.1007/s12328-023-01777-y

(DOI: 10.1007/s12328-023-01777-y, PubMed: 36856957) Yoshifumi Kida, Toshiya Okahisa, Yasushi Sato, Masahiro Bando, Shota Fujimoto, ma beibei, Tadahiko Nakagawa, Tomoyuki Kawaguchi, Fumika Nakamura, Koichi Okamoto, Hiroshi Miyamoto, Masahiro Sogabe, Koichi Tsuneyama and Tetsuji Takayama :
Urokinase-type plasminogen activator blockade ameliorates experimental colitis in mice.,
Scientific Reports, Vol.13, No.1, 2899, 2023.

(要約): Although several angiogenesis-related factors are reportedly involved in the pathogenesis of ulcerative colitis (UC), the mechanisms by which they contribute to disease are unclear. We first examined the expression of angiogenesis-related factors in inflamed colorectal tissue of UC patients using antibody array, and identified the 5 factors with highest expression, which included matrix metalloproteinase-8, urokinase-type plasminogen activator (uPA), angiostatin/plasminogen, hepatocyte growth factor and endoglin. Subsequent real-time PCR experiments using additional colorectal tissues revealed that uPA mRNA levels were significantly higher in inflamed tissues than in non-inflamed tissues, and significantly correlated with the severity of UC. Mirror section immunohistochemistry revealed that uPA was expressed in the neutrophils of inflamed colorectal tissues. We administered dextran sulfate sodium (DSS) in drinking water to uPA knockout (uPA) mice, and found that the disease activity index in uPA mice was marginally lower and the histological score in uPA mice was significantly lower than those in wild-type mice, suggesting the importance of uPA in colitis. When an uPA-selective inhibitor, UK122, was administered to DSS-treated C57BL6J mice, the disease activity index and histological score in those mice were significantly lower compared with control mice. Multiple cytokine/chemokine assay using colorectal tissues from uPA and UK122-treated mice revealed significantly lowered level of RANTES. In conclusion, uPA was highly expressed in neutrophils of the inflamed mucosa of UC patients, and the expression level correlated with the severity of UC. Genetic uPA deletion or pharmacological uPA blockade significantly ameliorated colitis in mice, concomitant with downregulation of RANTES.
(キーワード): Animals / Mice / Urokinase-Type Plasminogen Activator / Colitis / Colitis, Ulcerative / Serine Proteases / Colorectal Neoplasms
(徳島大学機関リポジトリ): ● Metadata: 118522
(出版サイトへのリンク): ● Publication site (DOI): 10.1038/s41598-023-29824-1
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36806262; ● Search Scopus @ Elsevier (PMID): 36806262; ● Search Scopus @ Elsevier (DOI): 10.1038/s41598-023-29824-1

(徳島大学機関リポジトリ: 118522, DOI: 10.1038/s41598-023-29824-1, PubMed: 36806262) Tetsu Tomonari, Joji Tani, Chikara Ogawa, Akihiro Deguchi, Tomonori Senoh, Akio Moriya, Hiroshi Shibata, Hiroshi Fukuno, Hironori Tanaka, Takahiro Tanaka, Tatsuya Taniguchi, Masahiro Sogabe, Yutaka Kawano, Akihiro Morishita, Koichi Takaguchi, Hiroshi Miyamoto, Yasushi Sato, Tsutomu Masaki and Tetsuji Takayama :
Multicenter retrospective study of Initial treatment outcome and feasibility of initiating dose reduction of cabozantinib in unresectable hepatocellular carcinoma.,
Hepatology Research, Vol.53, No.2, 172-178, 2023.

(要約): Cabozantinib (CAB), a multiple kinase inhibitor, has been approved for use in patients with previously treated unresectable hepatocellular carcinoma (uHCC). However, real-world clinical data are lacking, particularly clinical data regarding dose modifications of CAB. We analyzed the clinical outcomes of CAB in uHCC and compared treatment outcomes between the full- and reduced-dose groups. This multicenter, observational study included patients with uHCC who were treated with CAB from March 2021 to April 2022. Patient characteristics, efficacy, and safety were compared between the full- and reduced-dose groups. Twenty-six patients from eight institutes were analyzed. Cabozantinib was administered as a third-line or later treatment in 25 (96.2%) patients and postimmunotherapy in 21 (80.5%) patients. There were 15 patients in the full-dose group (60 mg CAB) and 11 in the reduced-dose group (40 or 20 mg CAB). The objective response rate (ORR) and disease control rate (DCR) were not significantly different between the two groups. The ORR was 6.7% for the full-dose group and 9.1% for the reduced-dose group, and the DCR was 53.4% and 81.8%, respectively. Progression-free survival analysis showed no significant differences between the two groups. The incidence of decreased appetite, fatigue, and diarrhea, and the rate of discontinuation and dose reduction, was significantly higher in the full-dose group. Our study suggests that the efficacy and safety of CAB in real-world clinical practice are comparable to those of the phase III trial (CELESTIAL), and that dose reduction of CAB may be a safer treatment option.
(出版サイトへのリンク): ● Publication site (DOI): 10.1111/hepr.13845
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36214071; ● Search Scopus @ Elsevier (PMID): 36214071; ● Search Scopus @ Elsevier (DOI): 10.1111/hepr.13845

(DOI: 10.1111/hepr.13845, PubMed: 36214071) Tetsu Tomonari, Joji Tani, Yasushi Sato, Hironori Tanaka, Takahiro Tanaka, Tatsuya Taniguchi, Akihiro Morishita, Koichi Okamoto, Masahiro Sogabe, Hiroshi Miyamoto, Naoki Muguruma, Tsutomu Masaki and Tetsuji Takayama :
Initial therapeutic results of atezolizumab plus bevacizumab for unresectable advanced hepatocellular carcinoma and the importance of hepatic functional reserve.,
Cancer Medicine, Vol.12, No.3, 2646-2657, 2023.

(要約): We analyzed the association between the modified albumin-bilirubin (mALBI) grade and therapeutic efficacy of atezolizumab plus bevacizumab (Atezo+Bev) for the treatment of unresectable hepatocellular carcinoma (u-HCC). In this retrospective observational study, we included 71 u-HCC patients treated with Atezo+Bev between September 2020 and September 2021. Patients were grouped corresponding to the mALBI grade at the start of treatment (mALBI 1+2a or mALBI 2b+3) and analyzed for therapeutic effect and the transition rate to secondary treatment. According to the Response Evaluation Criteria in Solid Tumors, the overall response rate was significantly higher for the mALBI 1+2a group, than for the mALBI 2b+3 group, with 26.2% and 3.4%, respectively. The progression-free survival (PFS) was significantly longer in the mALBI 1+2a group (10.5 months) than in the mALBI 2b+3 group (3.0 months). In the multivariate analysis, an mALBI of 1+2a was found to be an independent factor of PFS. The rate of second-line treatment with multi-targeted agents was also significantly higher in the mALBI 1+2a group. In real-world practice, Atezo+Bev treatment might have higher therapeutic efficacy in u-HCC patients with mALBI 1+2a.
(徳島大学機関リポジトリ): ● Metadata: 117987
(出版サイトへのリンク): ● Publication site (DOI): 10.1002/cam4.5145
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 35964253; ● Search Scopus @ Elsevier (PMID): 35964253; ● Search Scopus @ Elsevier (DOI): 10.1002/cam4.5145

(徳島大学機関リポジトリ: 117987, DOI: 10.1002/cam4.5145, PubMed: 35964253) Yasushi Sato, Yasuyuki Okada, Yasuteru Fujino, Tomoyuki Kawaguchi, Yoshifumi Kida, Yasuhiro Mitsui, Hironori Tanaka, Tetsu Tomonari, Shinji Kitamura, Koichi Okamoto, Yutaka Kawano, Hiroshi Miyamoto, Masahiro Sogabe and Tetsuji Takayama :
Clinical Outcomes of Comprehensive Genomic Profiling Tests for Gastrointestinal Cancers: Experience from Tokushima University Hospital.,
The Journal of Medical Investigation : JMI, Vol.70, No.1.2, 154-159, 2023.

(要約): In Japan, cancer genome profiling (CGP) for cancer patients without standard treatment has been covered by public insurance since June 2019. This study analyzed data of 122 patients with gastrointestinal tumors who underwent CGP to clarify cancer genome medicine's current status and possible problems at the Tokushima University Hospital. The major types of cancer included pancreatic (n=30), colorectal (n=25), biliary tract (n=15), gastric (n=11), and hepatocellular carcinoma (n=8). CGP tests included F1CDx in 70 patients (57%), F1LCDx in 36 (30%), TSO500 in 14 (11%), and NCC Oncopanel in 2 (2%). Actionable gene alterations were identified in 72 patients (59%), but only 5 patients (4%) were treated for pancreatic (n=1), colorectal (n=3), and small bowel cancers (n=1). The main reasons for not receiving genotype-matched therapy included the lack of appropriate drugs or clinical trials that matched the actionable gene alterations (n=40) and the inability to participate in clinical trials (n=10). There is still not a sufficient number of patients receiving genotype-matched treatment for gastrointestinal cancers. To promote cancer genome medicine in regional areas, attempts to improve access to genotype-matched therapies are required, as well as to promote the development of new molecular-targeted drugs and clinical trials for these drugs. J. Med. Invest. 70 : 154-159, February, 2023.
(キーワード): Humans / Gastrointestinal Neoplasms / Neoplasms / Colorectal Neoplasms / Genomics / Hospitals / Japan
(徳島大学機関リポジトリ): ● Metadata: 118346
(出版サイトへのリンク): ● Publication site (DOI): 10.2152/jmi.70.154
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 37164713; ● Search Scopus @ Elsevier (PMID): 37164713; ● Search Scopus @ Elsevier (DOI): 10.2152/jmi.70.154

(徳島大学機関リポジトリ: 118346, DOI: 10.2152/jmi.70.154, PubMed: 37164713) Megumi Yamasaki, Yasushi Sato, Koichi Okamoto, Akira Fukuya, Tomoyuki Kawaguchi, Kazuyoshi Noda, Kaizo Kagemoto, Yasuhiro Mitsui, Hiroshi Miyamoto and Tetsuji Takayama :
Two cases of anal squamous cell carcinoma achieving complete response after docetaxel + cisplatin + S1 (DCS) induction chemotherapy followed by chemoradiation.,
Clinical Journal of Gastroenterology, Vol.16, No.2, 180-186, 2022.

(要約): Anal squamous cell carcinoma (ASCC) is an uncommon tumor. However, its incidence is increasing worldwide. Surgical resection of locally advanced cases requires permanent anal prosthesis. Thus, chemoradiotherapy (CRT) is preferred as the first-line treatment; however, high local recurrence rate remains an issue. Here, we describe two cases of locally advanced ASCC treated with docetaxel + cisplatin + S-1 (DCS) followed by CRT with S-1 that showed complete response. The two patients, aged 69 and 65 years, were diagnosed with ASCC (cStage IIIB) at our hospital. Due to extensive lymph node metastases, the patients were treated with triple induction chemotherapy (DCS) followed by CRT with S-1. Positron emission tomography/computed tomography performed six months after starting the treatment showed disappearance of tumors, indicating a complete response. The patients continued to receive S-1 for one year and achieved relapse-free long-term survival since the completion of treatment. Therefore, induction chemotherapy with DCS, prior to CRT with S-1 may benefit patients with locally advanced ASCC.
(出版サイトへのリンク): ● Publication site (DOI): 10.1007/s12328-022-01736-z
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36409453; ● Search Scopus @ Elsevier (PMID): 36409453; ● Search Scopus @ Elsevier (DOI): 10.1007/s12328-022-01736-z

(DOI: 10.1007/s12328-022-01736-z, PubMed: 36409453) Masahiro Sogabe, Toshiya Okahisa, Miwako Kagawa, Hiroyuki Ueda, Kaizo Kagemoto, Hironori Tanaka, Yoshifumi Kida, Tetsu Tomonari, Tatsuya Taniguchi, Hiroshi Miyamoto, Yasushi Sato, Masahiko Nakasono and Tetsuji Takayama :
Influence of Alcohol Consumption on the Development of Erosive Esophagitis in Both Sexes: A Longitudinal Study.,
Nutrients, Vol.14, No.22, 4760, 2022.

(要約): The influence of changes in alcohol consumption on erosive esophagitis (EE) development in both sexes is unclear. This observational study investigated sex differences in the influence of alcohol consumption on EE development, and included 2582 patients without EE at baseline from 13,448 patients who underwent >2 health check-ups over >1 year. The rates of non-drinkers who started drinking, and drinkers who abstained from drinking, who increased, and who decreased their weekly alcohol consumption were 7.2%, 9.7%, 14.7%, and 24.1% and 7.3%, 17.8%, 12.8%, and 39.0% in men and women, respectively. In the final cohort, 211/1405 (15.0%) men and 79/1177 (6.7%) women newly developed EE. The odds ratio (OR) for drinking in EE development was 1.252 (95% confidence interval (CI), 0.907-1.726) among men and 1.078 (95% CI, 0.666-1.747) among women. Among men aged <50 years, the OR for drinking ≥70 g/week in EE development was 2.825 (95% CI, 1.427-5.592), whereas among women, the OR for drinking ≥140 g/week in EE development was 3.248 (95% CI, 1.646-6.410). Among participants aged <50 years, the OR for daily drinking in EE development was 2.692 (95% CI, 1.298-5.586) among men and 4.030 (95% CI, 1.404-11.57) among women. The influence of alcohol consumption on EE development differed between the sexes. We recommend no alcohol consumption for individuals aged <50 years to avoid EE development. Daily drinkers should be assessed for EE development.
(キーワード): Humans / Male / Female / Longitudinal Studies / Alcohol Drinking / Esophagitis / Sexual Behavior / Cohort Studies / Peptic Ulcer
(徳島大学機関リポジトリ): ● Metadata: 118071
(出版サイトへのリンク): ● Publication site (DOI): 10.3390/nu14224760
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36432447; ● Search Scopus @ Elsevier (PMID): 36432447; ● Search Scopus @ Elsevier (DOI): 10.3390/nu14224760

(徳島大学機関リポジトリ: 118071, DOI: 10.3390/nu14224760, PubMed: 36432447) 和田浩典, 藤野泰輝, 影本開三, 喜田慶史, 岡田泰行, 三井康裕, 岡本耕一, 佐藤康史, 坂東良美, 宮本弘志, 高山哲治 :
がん遺伝子パネル検査を契機にHER2陽性が判明しTrastuzumab投与により長期生存が得られた進行胃癌の1例.,
日本消化器病学会雑誌, Vol.119, No.10, 937-945, 2022年.

(要約): Intratumoral HER2 heterogeneity is a well-described gastric cancer feature and may explain many false-negative results related to this oncogene. An 81-year-old man was diagnosed at our hospital with stage IV gastric cancer with multiple lymph node metastases. Immunohistochemistry (IHC) analysis indicated that the primary tumor was HER2-negative. After a chemotherapy course, we submitted a pretreatment biopsy specimen for comprehensive cancer genome profiling (CGP) to determine the last-line therapy. This revealed HER2 amplification. The specimen was reevaluated using fluorescence in situ hybridization and IHC with deeper-cut specimens, which confirmed that the tumor was indeed HER2-positive. Therefore, the patient was treated with chemotherapy plus trastuzumab, which elicited tumor shrinkage and conferred long-term survival. Our current data underscore the CGP importance, which can provide more accurate tumor profilings and inform subsequent treatment decisions.
(キーワード): がん遺伝子パネル検査 / Trastuzumab / HER2陽性胃癌
(出版サイトへのリンク): ● Publication site (DOI): 10.11405/nisshoshi.119.937
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36216544; ● CiNii @ 国立情報学研究所 (CRID): 1390293710918867840; ● Search Scopus @ Elsevier (PMID): 36216544; ● Search Scopus @ Elsevier (DOI): 10.11405/nisshoshi.119.937

(DOI: 10.11405/nisshoshi.119.937, PubMed: 36216544, CiNii: 1390293710918867840) Hideki Ishikawa, Masayoshi Yamada, Yasushi Sato, Shinji Tanaka, Chino Akiko, Masahiro Tajika, Hisashi Doyama, Tetsuji Takayama, Yoshio Ohda, Takahiro Horimatsu, Yasushi Sano, Kohji Tanakaya, Hiroaki Ikematsu, Yoshihisa Saida, Hideyuki Ishida, Yoji Takeuchi, Hiroshi Kashida, Shinsuke Kiriyama, Shinichiro Hori, Kyowon Lee, Jun Tashiro, Nozomu Kobayashi, Takeshi Nakajima, Sadao Suzuki and Michihiro Mutoh :
Intensive endoscopic resection for downstaging of polyp burden in patients with familial adenomatous polyposis (J-FAPP Study III): a multicenter prospective interventional study.,
Endoscopy, Vol.55, No.4, 344-352, 2022.

(要約): 222 patients were eligible, of whom 166 had not undergone colectomy, 46 had undergone subtotal colectomy with ileorectal anastomosis, and 10 had undergone partial resection of the large intestine. During the intervention period, five patients (2.3 %, 95 % confidence interval [CI] 0.74 %-5.18 %) underwent colectomy, and three patients died. Completion of the 5-year intervention period without colectomy was confirmed in 150 /166 patients who had not undergone colectomy (90.4 %, 95 %CI 84.8 %-94.4 %) and in 47 /56 patients who had previously undergone colectomy (83.9 %, 95 %CI 71.7 %-92.4 %).
(徳島大学機関リポジトリ): ● Metadata: 118007
(出版サイトへのリンク): ● Publication site (DOI): 10.1055/a-1945-9120
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36216266; ● Search Scopus @ Elsevier (PMID): 36216266; ● Search Scopus @ Elsevier (DOI): 10.1055/a-1945-9120

(徳島大学機関リポジトリ: 118007, DOI: 10.1055/a-1945-9120, PubMed: 36216266) Masahiro Sogabe, Toshiya Okahisa, Takeshi Kurihara, Miwako Kagawa, Hiroyuki Ueda, Tomoyuki Kawaguchi, Akira Fukuya, Kaizoh Kagemoto, Hironori Tanaka, Yoshifumi Kida, Tetsu Tomonari, Tatsuya Taniguchi, Koichi Okamoto, Hiroshi Miyamoto, Yasushi Sato, Masahiko Nakasono and Tetsuji Takayama :
Comparison of the role of alcohol consumption and qualitative abdominal fat on NAFLD and MAFLD in males and females.,
Scientific Reports, Vol.12, No.1, 16048, 2022.

(要約): The clinical difference between nonalcoholic fatty liver disease (NAFLD) and metabolic-associated fatty liver disease (MAFLD) between the two sexes is unclear. This study aimed to determine the influences of alcohol consumption and qualitative abdominal fat between male and female patients with NAFLD and MAFLD. This cross-sectional study examined 11,766 participants who underwent health check-ups comparing lifestyle habits, biochemical features, and noninvasive liver fibrosis scores, between non-MAFLD and MAFLD groups. Furthermore, differences in alcohol consumption and qualitative abdominal fat were examined between male and female patients with NAFLD and MAFLD. The prevalence of metabolic dysregulation, ratio of visceral fat area to subcutaneous fat area, and noninvasive liver fibrosis scores were significantly higher in male patients with MAFLD than in those with NAFLD (p < 0.05), but these were not significantly different in female patients. Among male patients with an alcohol consumption of > 70 g/week, several noninvasive liver fibrosis scores were significantly higher in the MAFLD group than in the NAFLD group (all p < 0.05). The influences of alcohol consumption and qualitative abdominal fat on NAFLD and MAFLD were different between sexes. The development of liver fibrosis should be considered in male patients with MAFLD who exceed mild drinking.
(キーワード): Alcohol Drinking / Cross-Sectional Studies / Female / Humans / Intra-Abdominal Fat / Liver Cirrhosis / Male / Non-alcoholic Fatty Liver Disease
(徳島大学機関リポジトリ): ● Metadata: 117853
(出版サイトへのリンク): ● Publication site (DOI): 10.1038/s41598-022-20124-8
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36163355; ● Search Scopus @ Elsevier (PMID): 36163355; ● Search Scopus @ Elsevier (DOI): 10.1038/s41598-022-20124-8

(徳島大学機関リポジトリ: 117853, DOI: 10.1038/s41598-022-20124-8, PubMed: 36163355) Hironori Wada, Yasushi Sato, Shota Fujimoto, Koichi Okamoto, Masahiro Bando, Tomoyuki Kawaguchi, Hiroshi Miyamoto, Naoki Muguruma, Katsuhisa Horimoto, Yui Matsuzawa, Michihiro Mutoh and Tetsuji Takayama :
Resveratrol inhibits development of colorectal adenoma via suppression of LEF1; comprehensive analysis with connectivity map.,
Cancer Science, Vol.113, No.12, 4374-4384, 2022.

(要約): Although many chemopreventive studies on colorectal tumors have been reported, no effective and safe preventive agent is currently available. We searched for candidate preventive compounds against colorectal tumor comprehensively from United States Food and Drug Administration (FDA)-approved compounds by using connectivity map (CMAP) analysis coupled with in vitro screening with colorectal adenoma (CRA) patient-derived organoids (PDOs). We generated CRA-specific gene signatures based on the DNA microarray analysis of CRA and normal epithelial specimens, applied them to CMAP analysis with 1309 FDA-approved compounds, and identified 121 candidate compounds that should cancel the gene signatures. We narrowed them down to 15 compounds, and evaluated their inhibitory effects on the growth of CRA-PDOs in vitro. We finally identified resveratrol, one of the polyphenolic phytochemicals, as a compound showing the strongest inhibitory effect on the growth of CRA-PDOs compared with normal epithelial PDOs. When resveratrol was administered to Apc mice at 15 or 30 mg/kg, the number of polyps (adenomas) was significantly reduced in both groups compared with control mice. Similarly, the number of polyps (adenomas) was significantly reduced in azoxymethane-injected rats treated with 10 or 100 mg/resveratrol compared with control rats. Microarray analysis of adenomas from resveratrol-treated rats revealed the highest change (downregulation) in expression of LEF1, a key molecule in the Wnt signaling pathway. Treatment with resveratrol significantly downregulated the Wnt-target gene (MYC) in CRA-PDOs. Our data demonstrated that resveratrol can be the most effective compound for chemoprevention of colorectal tumors, the efficacy of which is mediated through suppression of LEF1 expression in the Wnt signaling pathway.
(キーワード): Mice / Rats / Animals / Resveratrol / Adenoma / Colorectal Neoplasms / Wnt Signaling Pathway / Chemoprevention / Lymphoid Enhancer-Binding Factor 1
(徳島大学機関リポジトリ): ● Metadata: 117988
(出版サイトへのリンク): ● Publication site (DOI): 10.1111/cas.15576
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36082704; ● Search Scopus @ Elsevier (PMID): 36082704; ● Search Scopus @ Elsevier (DOI): 10.1111/cas.15576

(徳島大学機関リポジトリ: 117988, DOI: 10.1111/cas.15576, PubMed: 36082704) Beibei Ma, Hiroyuki Ueda, Koichi Okamoto, Masahiro Bando, Shota Fujimoto, Yasuyuki Okada, Tomoyuki Kawaguchi, Hironori Wada, Hiroshi Miyamoto, Mitsuo Shimada, Yasushi Sato and Tetsuji Takayama :
TIMP1 promotes cell proliferation and invasion capability of right-sided colon cancers via the FAK/Akt signaling pathway.,
Cancer Science, Vol.113, No.12, 4244-4257, 2022.

(要約): Although right-sided colorectal cancer (CRC) shows a worse prognosis than left-sided CRC, the underlying mechanism remains unclear. We established patient-derived organoids (PDOs) from left- and right-sided CRCs and directly compared cell proliferation and invasion capability between them. We then analyzed the expression of numerous genes in signal transduction pathways to clarify the mechanism of the differential prognosis. Cell proliferation activity and invasion capability in right-sided cancer PDOs were significantly higher than in left-sided cancer PDOs and normal PDOs, as revealed by Cell Titer Glo and transwell assays, respectively. We then used quantitative RT-PCR to compare 184 genes in 30 pathways among right-sided and left-sided cancer and normal PDOs and found that the TIMP1 mRNA level was highest in right-sided PDOs. TIMP1 protein levels were upregulated in right-sided PDOs compared with normal PDOs but was downregulated in left-sided PDOs. TIMP1 knockdown with shRNA significantly decreased cell proliferation activity and invasion capability in right-sided PDOs but not in left-sided PDOs. Moreover, TIMP1 knockdown significantly decreased pFAK and pAkt expression levels in right-sided PDOs but not in left-sided PDOs. A database analysis of The Cancer Genome Atlas revealed that TIMP1 expression in right-sided CRCs was significantly higher than in left-sided CRCs. Kaplan-Meier survival analysis showed significantly shorter overall survival in high-TIMP1 patients versus low-TIMP1 patients with right-sided CRCs but not left-sided CRCs. Our data suggest that TIMP1 is overexpressed in right-sided CRCs and promotes cell proliferation and invasion capability through the TIMP1/FAK/Akt pathway, leading to a poor prognosis. The TIMP1/FAK/Akt pathway can be a target for therapeutic agents in right-sided CRCs.
(キーワード): Humans / Prognosis / Signal Transduction / Colorectal Neoplasms / Colonic Neoplasms / Cell Proliferation / Tissue Inhibitor of Metalloproteinase-1
(徳島大学機関リポジトリ): ● Metadata: 117615
(出版サイトへのリンク): ● Publication site (DOI): 10.1111/cas.15567
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36073574; ● Search Scopus @ Elsevier (PMID): 36073574; ● Search Scopus @ Elsevier (DOI): 10.1111/cas.15567

(徳島大学機関リポジトリ: 117615, DOI: 10.1111/cas.15567, PubMed: 36073574) Fumika Nakamura, Yasushi Sato, Koichi Okamoto, Yasuteru Fujino, Yasuhiro Mitsui, kaizo kagemoto, Tomoyuki Kawaguchi, Hiroshi Miyamoto, Naoki Muguruma, Tomoko Sonoda, Koichi Tsuneyama and Tetsuji Takayama :
Colorectal carcinoma occurring via the adenoma-carcinoma pathway in patients with serrated polyposis syndrome.,
Journal of Gastroenterology, Vol.57, No.4, 286-299, 2022.

(要約): Although serrated polyposis syndrome (SPS) is associated with an increased colorectal cancer (CRC) risk, the carcinogenic mechanisms remain unknown. We investigated clinicopathological characteristics and genetic abnormalities in colorectal polyps and CRC to elucidate carcinogenic mechanisms in SPS. We retrospectively analyzed clinicopathological features of colorectal polyps in 44 SPS patients, and examined mutations of genes including APC, RAS, BRAF, and TP53, and microsatellite instability (MSI) in CRC tissues. Of the 44 patients, 25 (56%) fulfilled WHO criterion 1, 11 (25%) fulfilled criterion 2, and 8 (18%) fulfilled both. A total of 956 polyps were observed; 642 (67%) hyperplastic polyps (HP), 204 (21%) sessile serrated lesions (SSL), 10 (1%) traditional serrated adenoma (TSA), and 100 (11%) adenomas. The median numbers of polyps (/patient) were 10.5 (IQR 2.75-23) HPs, 4.0 (2.0-6.0) SSLs, 0 (0-0) TSA, and 1 (0-3.3) adenoma. SSL and HP located preferentially in the proximal and distal colon, respectively. Twenty-two CRCs were found in 18 patients. Based on the histological coexistence of SSL/TSA, BRAF mutation and MSI, 5 CRCs (26%) were classified as serrated-neoplasia pathway. Conversely, based on the coexistence of adenoma, APC/RAS and TP53 mutations, 11 CRCs (58%) were classified as adenoma-carcinoma pathway. The remaining three were unclassifiable. Most CRCs through adenoma-carcinoma pathway were located in the left-side colorectum and patients bearing those met criterion 2, characterized by many HP and advanced adenomas. Adenoma was a significant risk factor for CRC. Our results suggest that more than half of the CRCs, particularly those in the left-side colorectum, developed through the adenoma-carcinoma pathway in SPS patients. Adenoma was a risk factor for CRCs, suggesting its importance in colorectal carcinogenesis.
(キーワード): Adenoma / Carcinoma / Colonic Polyps / Colorectal Neoplasms / Humans / Intestinal Polyposis / Microsatellite Instability / Mutation / Proto-Oncogene Proteins B-raf / Retrospective Studies
(徳島大学機関リポジトリ): ● Metadata: 117614
(出版サイトへのリンク): ● Publication site (DOI): 10.1007/s00535-022-01858-8
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 35194694; ● Search Scopus @ Elsevier (PMID): 35194694; ● Search Scopus @ Elsevier (DOI): 10.1007/s00535-022-01858-8

(徳島大学機関リポジトリ: 117614, DOI: 10.1007/s00535-022-01858-8, PubMed: 35194694) Noriaki Murayama, Koichi Okamoto, Tadahiko Nakagawa, Jinsei Miyoshi, Kensei Nishida, Tomoyuki Kawaguchi, kaizo kagemoto, Shinji Kitamura, Beibei Ma, Hiroshi Miyamoto, Naoki Muguruma, Mitsuyasu Yano, Koichi Tsuneyama, Takahiro Fujimori, Yasushi Sato and Tetsuji Takayama :
miR-144-3p/miR-451a promotes lymphovascular invasion through repression of PTEN/p19 in rectal neuroendocrine tumors.,
Journal of Gastroenterology and Hepatology, Vol.37, No.5, 919-927, 2022.

(要約): Although rectal neuroendocrine tumor (NET-G1) have potential metastatic capability, even among small tumors, no predictive biomarker for invasion and metastasis has been reported. We analyzed microRNA (miRNA) expression profiles in rectal NET-G1 tissues with and without lymphovascular invasion (LVI). Moreover, we then investigated their target genes to clarify the mechanism of invasion/metastasis in NET-G1. miRNA array analysis was performed using seven rectal NET-G1 tissues with LVI and seven without LVI. miRNA expression was confirmed by quantitative real-time PCR. A NET cell line H727 was transfected with miRNA mimic or target gene small interfering RNA, and migration and invasion assays were performed. The expression levels of miR-144-3p and miR-451a were significantly higher in NET-G1 with LVI versus without LVI, as determined by miRNA array analysis and RT-qPCR. A significant correlation was observed between miR-144-3p and miR-451a expression levels, strongly suggesting miR144/451 cluster overexpression in NET-G1 with LVI. Bioinformatic analysis of target genes revealed that miR-144-3p and miR-451a directly interact with PTEN and p19 mRNA, respectively. Immunohistochemistry revealed significantly lower expression of PTEN and p19 in NET-G1 tissues with LVI than in those without LVI. The miR-144-3p and miR-451a mimic significantly increased cell migration/invasion capability, respectively. Knockdown of PTEN and p19 induced significant augmentation of cell invasion and migration capability, respectively. Our data suggest that overexpression of miR-144/miR-451 cluster promotes LVI via repression of PTEN and p19 in rectal NET-G1 cells. miR-144/451 cluster may be a novel biomarker for predicting invasion/metastasis in rectal NET-G1.
(キーワード): Biomarkers / Cell Line, Tumor / Cell Movement / Cell Proliferation / Gene Expression Regulation, Neoplastic / Humans / MicroRNAs / Neuroendocrine Tumors / PTEN Phosphohydrolase / Rectal Neoplasms
(徳島大学機関リポジトリ): ● Metadata: 117699
(出版サイトへのリンク): ● Publication site (DOI): 10.1111/jgh.15833
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 35332577; ● Search Scopus @ Elsevier (PMID): 35332577; ● Search Scopus @ Elsevier (DOI): 10.1111/jgh.15833

(徳島大学機関リポジトリ: 117699, DOI: 10.1111/jgh.15833, PubMed: 35332577) Satoshi Teramae, Naoki Muguruma, Koichi Okamoto, Kumiko Oseto, Ryutaro Nishikawa, Takayuki Tanoue, Keiji Hirata, Shunichi Yanai, Takayuki Matsumoto, Seiji Shimizu, Jun Miwa, Yu Sakaki, Kazuo Yashima, Hiroyuki Ohnuma, Yasushi Sato, Yoshitaka Kitayama, Yoshio Ohda, Atsushi Yamauchi, Yoji Sanomura, Kumiko Tanaka, Yoshiaki Kubo, Hideki Ishikawa, Yoshimi Bando, TOmoko Sonoda and Tetsuji Takayama :
Cancer risk and genotype-phenotype correlation in Japanese patients with Cowden syndrome.,
International Journal of Clinical Oncology, Vol.27, No.4, 639-647, 2022.

(要約): Cowden syndrome (CS) is an autosomal-dominant hereditary disorder caused by a germline PTEN variant and characterized by multiple hamartomas and a high risk of cancers. However, no detailed data on CS in Asian patients nor genotype-phenotype correlation have been reported. We performed the first Japanese nationwide questionnaire survey on CS and obtained questionnaire response data on 49 CS patients. Patients included 26 females (median age 48 years). The incidence of breast, thyroid, endometrium, and colorectal cancer was 32.7%, 12.2%, 19.2% (among females), and 6.1%, respectively. The incidence of any cancers was relatively high among all patients (46.9%, 23/49), and particularly female patients (73.1%, 19/26), compared with previous reports from Western countries. Gastrointestinal (GI) polyps were more frequently found throughout the GI tract compared with previous studies. PTEN variants were detected in 95.6% (22/23) of patients; 12 in the N-terminal region (11 in phosphatase domain) and 10 in the C-terminal (C2 domain) region. The incidence of cancer in the C2 domain group was significantly higher than in the N-terminal region (phosphatase) group. All female patients with C2 domain variant had breast cancer. Our data suggest that Japanese patients with CS, particularly female patients and patients with C2 domain variant may have a high risk of cancers.
(キーワード): Breast Neoplasms / Female / Genetic Association Studies / Hamartoma Syndrome, Multiple / Humans / Intestinal Polyps / Japan / Male / Middle Aged / PTEN Phosphohydrolase / Risk
(徳島大学機関リポジトリ): ● Metadata: 117152
(出版サイトへのリンク): ● Publication site (DOI): 10.1007/s10147-022-02116-w
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 35106660; ● Search Scopus @ Elsevier (PMID): 35106660; ● Search Scopus @ Elsevier (DOI): 10.1007/s10147-022-02116-w

(徳島大学機関リポジトリ: 117152, DOI: 10.1007/s10147-022-02116-w, PubMed: 35106660) Kumiko Tanaka, Yasushi Sato, Hideki Ishikawa, Naoki Muguruma, Satoshi Teramae, Yoji Takeuchi, Yasuhiro Mitsui, Koichi Okamoto, Hiroshi Miyamoto, Yoshimi Bando, Tomoko Sonoda, Naoki Omiya, Michihiro Mutoh and Tetsuji Takayama :
Small Intestinal Involvement and Genotype-Phenotype Correlation in Familial Adenomatous Polyposis.,
Techniques and Innovations in Gastrointestinal Endoscopy, Vol.24, No.1, 26-34, 2022.

(徳島大学機関リポジトリ): ● Metadata: 116979
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.tige.2021.10.001
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1360861291391377024; ● Summary page in Scopus @ Elsevier: 2-s2.0-85119353922

(徳島大学機関リポジトリ: 116979, DOI: 10.1016/j.tige.2021.10.001, CiNii: 1360861291391377024, Elsevier: Scopus) Yasushi Sato, Koichi Okamoto, Hiroshi Miyamoto and Tetsuji Takayama :
Chemotherapy in older adults with gastrointestinal cancer:Current practices and future directions in Japan.,
The Journal of Medical Investigation : JMI, Vol.69, No.1.2, 25-30, 2022.

(要約): Chemotherapy for cancer has significantly improved owing to the increasing number of effective chemotherapeutic agents and supportive care. Recently, the number of older cancer patients has rapidly increased owing to the aging of the global population. However, in most cases, it is difficult to treat those using similar dosages or schedules as that of younger patients because older patients generally have unfavorable factors, such as decreased performance status and physical and cognitive conditions, thus increasing the incidence of complications and side effects. Chemotherapy for gastrointestinal cancers has made significant progress in recent years with the introduction of molecular-targeted agents and immunotherapy. However, clinical trials showed limited evidence regarding the efficacy of chemotherapy in older cancer patients, accounting for half of all patients, making it difficult to develop a well-established treatment strategy. This review aimed to evaluate the current state of chemotherapy for gastrointestinal cancer in older adults. Furthermore, the limitations and future perspectives were discussed. J. Med. Invest. 69 : 25-30, February, 2022.
(キーワード): Aged / Antineoplastic Agents / Antineoplastic Combined Chemotherapy Protocols / Gastrointestinal Neoplasms / Humans / Japan
(徳島大学機関リポジトリ): ● Metadata: 117006
(出版サイトへのリンク): ● Publication site (DOI): 10.2152/jmi.69.25
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 35466142; ● CiNii @ 国立情報学研究所 (CRID): 1390291932640865024; ● Summary page in Scopus @ Elsevier: 2-s2.0-85128802446

(徳島大学機関リポジトリ: 117006, DOI: 10.2152/jmi.69.25, PubMed: 35466142, CiNii: 1390291932640865024, Elsevier: Scopus) Tetsu Tomonari, Yasushi Sato, Hironori Tanaka, Takeshi Mitsuhashi, Akihiro Hirao, Takahiro Tanaka, Tatsuya Taniguchi, Koichi Okamoto, Masahiro Sogabe, Hiroshi Miyamoto, Naoki Muguruma and Tetsuji Takayama :
Therapeutic efficacy of lenvatinib in nonviral unresectable hepatocellular carcinoma.,
JGH Open, Vol.5, No.11, 1275-1283, 2021.

(徳島大学機関リポジトリ): ● Metadata: 116741
(出版サイトへのリンク): ● Publication site (DOI): 10.1002/jgh3.12663
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1002/jgh3.12663

(徳島大学機関リポジトリ: 116741, DOI: 10.1002/jgh3.12663) Masanori Takehara, Hiroshi Miyamoto, Yasuteru Fujino, Tetsu Tomonari, Tatsuya Taniguchi, Shinji Kitamura, Koichi Okamoto, Masahiro Sogabe, Yasushi Sato, Naoki Muguruma, Yoshimi Bando and Tetsuji Takayama :
Long-Term Survival due to Chemotherapy including Paclitaxel in a Patient with Metastatic Primary Splenic Angiosarcoma.,
Case Reports in Gastroenterology, Vol.15, No.3, 910-918, 2021.

(要約): A primary splenic angiosarcoma is a rare type of soft tissue sarcoma and is associated with an extremely poor prognosis. In this study, we describe the case of a patient who was diagnosed with metastatic primary splenic angiosarcoma and survived for about 2 years. A 62-year-old female was referred to us for the treatment of splenic angiosarcoma with disseminated intravascular coagulation (DIC) and multiple liver and bone metastases. Paclitaxel therapy resulted in recovery from DIC and enabled her to continue sequential treatment through to sixth-line chemotherapy. We reviewed all splenic angiosarcoma case reports which were described as stage IV to date and compared with our case. From these data, we found that the median overall survival was 105 days, and the prognosis of splenic angiosarcoma of stage IV was worse than conventional case series. Splenectomy was performed in more patients than chemotherapy as a treatment. Moreover, various chemotherapeutic regimens were used. These data suggest that administering chemotherapy including paclitaxel to patients with splenic angiosarcoma might improve their prognosis.
(徳島大学機関リポジトリ): ● Metadata: 116721
(出版サイトへのリンク): ● Publication site (DOI): 10.1159/000519211
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34720843; ● Summary page in Scopus @ Elsevier: 2-s2.0-85117511057

(徳島大学機関リポジトリ: 116721, DOI: 10.1159/000519211, PubMed: 34720843, Elsevier: Scopus) Akihiro Hirao, Yasushi Sato, Hironori Tanaka, Kensei Nishida, Tetsu Tomonari, Misato Hirata, Masahiro Bando, Yoshifumi Kida, Takahiro Tanaka, Tomoyuki Kawaguchi, Hironori Wada, Tatsuya Taniguchi, Koichi Okamoto, Hiroshi Miyamoto, Naoki Muguruma, Toshihito Tanahashi and Tetsuji Takayama :
MiR-125b-5p is Involved in Sorafenib Resistance through Ataxin-1-Mediated Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma.,
Cancers, Vol.13, No.19, 4917, 2021.

(要約): The mechanism of resistance to sorafenib in hepatocellular carcinoma (HCC) remains unclear. We analyzed miRNA expression profiles in sorafenib-resistant HCC cell lines (PLC/PRF5-R1/R2) and parental cell lines (PLC/PRF5) to identify the miRNAs responsible for resistance. Drug sensitivity, migration/invasion capabilities, and epithelial-mesenchymal transition (EMT) properties were analyzed by biochemical methods. The clinical relevance of the target genes to survival in HCC patients were assessed using a public database. Four miRNAs were significantly upregulated in PLC/PRF5-R1/-R2 compared with PLC/PRF5. Among them, miR-125b-5p mimic-transfected PLC/PRF5 cells (PLC/PRF5-miR125b) and showed a significantly higher IC50 for sorafenib compared with controls, while the other miRNA mimics did not. PLC/PRF5-miR125b showed lower E-cadherin and higher Snail and vimentin expression-findings similar to those for PLC/PRF5-R2-which suggests the induction of EMT in those cells. PLC/PRF5-miR125b exhibited significantly higher migration and invasion capabilities and induced sorafenib resistance in an in vivo mouse model. Bioinformatic analysis revealed ataxin-1 as a target gene of miR-125b-5p. PLC/PRF5 cells transfected with ataxin-1 siRNA showed a significantly higher IC50, higher migration/invasion capability, higher cancer stem cell population, and an EMT phenotype. Median overall survival in the low-ataxin-1 patient group was significantly shorter than in the high-ataxin-1 group. In conclusion, miR-125b-5p suppressed ataxin-1 and consequently induced Snail-mediated EMT and stemness, leading to a poor prognosis in HCC patients.
(徳島大学機関リポジトリ): ● Metadata: 116647
(出版サイトへのリンク): ● Publication site (DOI): 10.3390/cancers13194917
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34638401; ● Search Scopus @ Elsevier (PMID): 34638401; ● Search Scopus @ Elsevier (DOI): 10.3390/cancers13194917

(徳島大学機関リポジトリ: 116647, DOI: 10.3390/cancers13194917, PubMed: 34638401) Shinji Kitamura, Naoki Muguruma, Koichi Okamoto, Kaizo Kagemoto, Yoshifumi Kida, Yasuhiro Mitsui, Hiroyuki Ueda, Tomoyuki Kawaguchi, Hiroshi Miyamoto, Yasushi Sato, Rika Aoki, Joji Shunto, Yoshimi Bando and Tetsuji Takayama :
Clinicopathological characteristics of early gastric cancer associated with autoimmune gastritis.,
JGH Open, Vol.5, No.10, 1210-1215, 2021.

(徳島大学機関リポジトリ): ● Metadata: 116931
(出版サイトへのリンク): ● Publication site (DOI): 10.1002/jgh3.12656
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34622010; ● Summary page in Scopus @ Elsevier: 2-s2.0-85114915216

(徳島大学機関リポジトリ: 116931, DOI: 10.1002/jgh3.12656, PubMed: 34622010, Elsevier: Scopus) Yasushi Sato, Akihiro Yoneda, Fumiko Shimizu, Miyuki Nishimura, Rai Shimoyama, Yasuyuki Tashiro, Wataru Kurata and Yoshiro Niitsu :
Resolution of fibrosis by siRNA HSP47 in vitamin A coupled liposomes induces regeneration of chronically injured livers.,
Journal of Gastroenterology and Hepatology, 2021.

(要約): These results demonstrated that regeneration of chronically damaged liver indeed occurs after anti-fibrosis treatment even under continuous exposure to hepatotoxin, which promises a significant benefit of the anti-fibrosis therapy for refractory liver diseases.
(出版サイトへのリンク): ● Publication site (DOI): 10.1111/jgh.15587
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34151462; ● Search Scopus @ Elsevier (PMID): 34151462; ● Search Scopus @ Elsevier (DOI): 10.1111/jgh.15587

(DOI: 10.1111/jgh.15587, PubMed: 34151462) Takahiro Kogawa, Yasushi Sato, Rai Shimoyama, Wataru Kurata, Yasuyuki Tashiro and Yoshiro Niitsu :
Chemoprevention of pancreatic cancer by inhibition of glutathione-S transferase P1.,
Investigational New Drugs, 2021.

(要約): Pancreatic cancer is among the most refractory malignancies with poor prognosis. Thus, preventive approaches, in addition to the development of novel therapeutic strategies are essential for this type of cancer. KRAS mutations occur very early in the development of pancreatic cancers and could be targeted for its prevention, yet specific inhibitors for mutated KRAS are lacking. Accordingly, Glutathione-S Transferase p1 (GSTP1), which we recently found to be an autocrine stimulator of mutated KRAS signaling, is predicted to be an alternative target for chemoprevention of pancreatic cancer. In this study, chemopreventive effects of O-Hexadecyl-γ-glutamyl-S-benzyl-cysteinyl-D-phenyl glycine-Ethylester (HGBPE), which we previously synthesized to inhibit GSTP1 activity, was analyzed for its effect on the prevention of a rat pancreatic carcinogenesis model induced by 7,12-dimethyl-benzanthracene (DMBA). Rats administered with DMBA were grouped into five cohorts. In the treated group I, which was treated neither with HGBPE nor vehicle, sequential appearance of precancerous lesions, ductal complexes, and adenocarcinoma was confirmed as previously reported. We also confirmed in this group that mutations of KRAS and expression of GSTP1 simultaneously occurred in the ductal complex. To rats of groups II and IV, HGBPE was administered, and vehicle to those of group III and V. In groups of II and IV, the incidence of both ductal complex and adenocarcinoma were significantly lower than those in groups III and V. These data clearly suggest the efficacy of HGBP as a potential chemopreventive agent for pancreatic cancer.
(出版サイトへのリンク): ● Publication site (DOI): 10.1007/s10637-021-01129-y
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34031785; ● Search Scopus @ Elsevier (PMID): 34031785; ● Search Scopus @ Elsevier (DOI): 10.1007/s10637-021-01129-y

(DOI: 10.1007/s10637-021-01129-y, PubMed: 34031785) Masahiro Sogabe, Toshiya Okahisa, Takeshi Kurihara, Miwako Kagawa, Kaizoh Kagemoto, Yoshifumi Kida, Tetsu Tomonari, Tatsuya Taniguchi, Koichi Okamoto, Hiroshi Miyamoto, Yasushi Sato, Masahiko Nakasono and Tetsuji Takayama :
Differences in Several Factors in the Development of Erosive Esophagitis Among Patients at Various Stages of Metabolic Syndrome: A Cross-Sectional Study.,
Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy, Vol.14, 1589-1600, 2021.

(徳島大学機関リポジトリ): ● Metadata: 116294
(出版サイトへのリンク): ● Publication site (DOI): 10.2147/DMSO.S298326
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 33883913; ● Summary page in Scopus @ Elsevier: 2-s2.0-85104815967

(徳島大学機関リポジトリ: 116294, DOI: 10.2147/DMSO.S298326, PubMed: 33883913, Elsevier: Scopus) Hideki Ishikawa, Michihiro Muto, Yasushi Sato, Hisashi Doyama, Masahiro Tajika, Shinji Tanaka, Takahiro Horimatsu, Yoji Takeuchi, Hiroshi kashida, Jun Tashiro, Yasumasa Ezoe, Takeshi Nakajima, Hiroaki Ikemitsu, Shinichiro Hori, Sadao Suzuki, Takahiro Otani, Tetsuji Takayama, Yoshio Ohda, Kanae Mure, Keiji Wakabayashi and Toshiyuki Sakai :
Chemoprevention with low-dose aspirin, mesalazine, or both in patients with familial adenomatous polyposis without previous colectomy (J-FAPP Study IV): a multicentre, double-blind, randomised, two-by-two factorial design trial.,
The Lancet. Gastroenterology & Hepatology, Vol.6, No.6, 474-481, 2021.

(要約): The only established treatment for preventing colorectal cancer in patients with familial adenomatous polyposis (FAP) is colectomy, which greatly reduces patient quality of life. Thus, an alternative method is warranted. In this trial, we aimed to clarify the individual and joint effects of low-dose aspirin and mesalazine on the recurrence of colorectal polyps in Japanese patients with FAP. This was a randomised, double-blind, placebo-controlled, multicentre trial with a two-by-two factorial design done in 11 centres in Japan. Eligible patients were aged 16-70 years and had a history of more than 100 adenomatous polyps in the large intestine, without a history of colectomy. Before the study, patients underwent endoscopic removal of all colorectal polyps of at least 5·0 mm in diameter. Randomisation was done with a minimisation method with a random component to balance the groups with respect to the adjustment factors of sex, age (<30 years vs ≥30 years), or smoking status at the time of entry. Patients and researchers were masked to the treatment group. There were four groups: aspirin (100 mg per day) plus mesalazine (2 g per day), aspirin (100 mg per day) plus mesalazine placebo, aspirin placebo plus mesalazine (2 g per day), or aspirin placebo plus mesalazine placebo. Treatment was continued until 1 week before 8 month colonoscopy. The primary endpoint was the incidence of colorectal polyps of at least 5·0 mm at 8 months and was assessed in the intention-to-treat population. Safety was assessed in the ITT population. We also did a per-protocol analysis including only patients who took at least 70% of the allocated study drug. This trial is registered with the UMIN Clinical Trials Registry, number UMIN000018736, and is complete. Between Sept 25, 2015, and March 13, 2017, 104 patients were randomly assigned to receive either aspirin or aspirin placebo (n=52) or mesalazine or mesalazine placebo (n=52). Two patients withdrew from the aspirin plus mesalazine placebo group. 26 (50%) of 52 patients who received no aspirin had colorectal polyps of at least 5·0 mm at 8 months, as did 15 (30%) of the 50 patients who received any aspirin, 21 (42%) of the 50 patients who received no mesalazine, and 20 (38%) of the 52 patients who received any mesalazine. The adjusted odds ratio for polyp recurrence was 0·37 (95% CI 0·16-0·86) in the patients who received any aspirin and 0·87 (95% CI 0·38-2·00) in any who received mesalazine. The most common adverse events were grade 1-2 upper gastrointestinal symptoms in three (12%) of 26 patients who received aspirin plus mesalazine, one (4%) of 24 patients who received aspirin plus mesalazine placebo, and one (4%) of 26 patients who received mesalazine plus aspirin placebo. There was one grade 4 event in the mesalazine plus aspirin placebo group, but not related to the treatment. Low-dose aspirin safely suppressed the recurrence of colorectal polyps larger than 5·0 mm in patients with FAP. These results suggest an effect of low-dose aspirin for FAP and could be an alternative method for preventing colorectal cancer in FAP. Japan Agency for Medical Research and Development.
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/S2468-1253(21)00018-2
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 33812492; ● Search Scopus @ Elsevier (PMID): 33812492; ● Search Scopus @ Elsevier (DOI): 10.1016/S2468-1253(21)00018-2

(DOI: 10.1016/S2468-1253(21)00018-2, PubMed: 33812492) Tetsu Tomonari, Yasushi Sato, Joji Tani, Akira Hirose, Chikara Ogawa, Akihiro Morishita, Hironori Tanaka, Takahiro Tanaka, Tatsuya Taniguchi, Koichi Okamoto, Masahiro Sogabe, Hiroshi Miyamoto, Naoki Muguruma, Kazushige Uchida, Tsutomu Masaki and Tetsuji Takayama :
Comparison of therapeutic outcomes of Sorafenib and Lenvatinib as primary treatments for hepatocellular carcinoma with a focus on molecular-targeted agent sequential therapy: A propensity score-matched analysis.,
Hepatology Research, Vol.51, No.4, 472-481, 2021.

(要約): The optimal choice between sorafenib (SOR) or lenvatinib (LEN) as the first-line treatment for unresectable hepatocellular carcinoma (u-HCC) remains debatable. Using propensity score matching, this study compares the outcomes of SOR and LEN in the molecular-targeted agent (MTA) sequential treatment of u-HCC patients. This retrospective, multicenter, observational study recruited 137 u-HCC patients who underwent primary treatment with LEN (n = 52) or SOR (n = 85) between June 2017 and June 2020 after regorafenib was approved as the secondary treatment for u-HCC. Propensity score matching was used to reduce confounding, resulting in the selection of 104 patients (n = 52 for the SOR and LEN cohorts). The median overall survival was 21.8 months for LEN and 20.4 months for SOR. LEN exhibited significantly greater therapeutic efficacy as compared to SOR (objective response rate: 3.8% [SOR] vs. 42.3% [LEN], P <0.01; progression-free survival: 10 months [LEN] vs. 5.1 months [SOR], P <0.01). No significant intergroup differences were noted in the rate of transition to secondary MTA treatments (SOR: 58.7%; LEN: 48.4%), adverse events (SOR: 86%; LEN: 95%), and maintenance of the Child-Pugh (CP) score during treatment. Compared to non-MTA treatments, secondary MTA treatment achieved a greater improvement in survival ( 4.3 months vs. 2.8 months, P=0.0047). Multivariate analysis demonstrated that the CP score (P <0.01) and alpha-fetoprotein level (P <0.01) were independent prognostic factors. Both SOR and LEN treatments showed a clinically comparable therapeutic efficacy as the first-line treatments for u-HCC patients in an MTA sequential therapy.
(出版サイトへのリンク): ● Publication site (DOI): 10.1111/hepr.13597
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 33238074; ● Search Scopus @ Elsevier (PMID): 33238074; ● Search Scopus @ Elsevier (DOI): 10.1111/hepr.13597

(DOI: 10.1111/hepr.13597, PubMed: 33238074) Hiroyuki Ohnuma, Yasushi Sato, Naoki Onoyama, Kota Hamaguchi, Naotaka Hayasaka, Masanori Sato, Kazuyuki Murase, Kohichi Takada, Koji Miyanishi, Takeshi Murakami, Tatsuya Ito, Takayuki Nobuoka, Ichiro Takemasa and Junji Kato :
Survival benefit of conversion surgery after intensive chemotherapy for unresectable metastatic gastric cancer: a propensity score-matching analysis.,
Journal of Cancer Research and Clinical Oncology, Vol.147, No.8, 2385-2396, 2021.

(要約): Of 175 cases, 61 (34.9%) underwent CS. R0 resection was obtained in 85.2%. After matching, 44 pairs were selected; there were no significant differences in baseline covariants. Group CS had a significantly better median overall survival (OS) (18.8 vs. 46.0 months, p < 0.001), and prolonged progression-free survival (7.4 vs. 25.8 months, p < 0.001). Subgroup analysis of OS showed a favorable trend for CS for almost all subgroups. Multivariate analysis revealed that good ECOG performance status and CS were associated with a longer OS.
(キーワード): Adenocarcinoma / Adult / Aged / Antineoplastic Combined Chemotherapy Protocols / Chemotherapy, Adjuvant / Cohort Studies / Combined Modality Therapy / Female / Gastrectomy / Humans / Male / Middle Aged / Neoplasm Metastasis / Propensity Score / Retrospective Studies / Risk Assessment / Stomach Neoplasms / Survival Analysis / Treatment Outcome
(出版サイトへのリンク): ● Publication site (DOI): 10.1007/s00432-021-03516-7
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 33534051; ● Search Scopus @ Elsevier (PMID): 33534051; ● Search Scopus @ Elsevier (DOI): 10.1007/s00432-021-03516-7

(DOI: 10.1007/s00432-021-03516-7, PubMed: 33534051) Hironori Tanaka, Yoshihito Saijyo, Tetsu Tomonari, Takahiro Tanaka, Tatsuya Taniguchi, Shusuke Yagi, Koichi Okamoto, Hiroshi Miyamoto, Masahiro Sogabe, Yasushi Sato, Naoki Muguruma, Koichi Tsuneyama, Masataka Sata and Tetsuji Takayama :
An Adult Case of Congenital Extrahepatic Portosystemic Shunt Successfully Treated with Balloon-occluded Retrograde Transvenous Obliteration,
Internal Medicine, Vol.60, No.12, 1839-1845, 2021.

(要約): A 42-year-old woman visited our hospital due to syncope. Contrast-enhanced CT revealed portosystemic shunt, portal vein hypoplasia, and multiple liver nodules. The histological examination of a liver biopsy specimen exhibited portal vein hypoplasia and revealed that the liver tumor was positive for glutamine synthetase. The patient was therefore diagnosed with congenital extrahepatic portosystemic shunt type II, and with focal nodular hyperplasia (FNH)-like nodules. She had the complication of severe portopulmonary hypertension and underwent complete shunt closure by balloon-occluded retrograde transvenous obliteration (B-RTO). The intrahepatic portal vein was well developed at 1 year after B-RTO, and multiple liver nodules completely regressed. Her pulmonary hypertension also improved.
(徳島大学機関リポジトリ): ● Metadata: 116336
(出版サイトへのリンク): ● Publication site (DOI): 10.2169/internalmedicine.5914-20
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 33456037; ● Search Scopus @ Elsevier (PMID): 33456037; ● Search Scopus @ Elsevier (DOI): 10.2169/internalmedicine.5914-20

(徳島大学機関リポジトリ: 116336, DOI: 10.2169/internalmedicine.5914-20, PubMed: 33456037) Sayo Takahashi, Koichi Okamoto, Toshihito Tanahashi, Shota Fujimoto, Tadahiko Nakagawa, Masahiro Bando, beibei ma, Tomoyuki Kawaguchi, Yasuteru Fujino, Yasuhiro Mitsui, Shinji Kitamura, Hiroshi Miyamoto, Yasushi Sato, Naoki Muguruma, Yoshimi Bando, Toshiro Sato, Takahiro Fujimori and Tetsuji Takayama :
S100P expression via DNA hypomethylation promotes cell growth in the sessile serrated adenoma/polyp-cancer sequence.,
Digestion, Vol.102, No.5, 789-802, 2021.

(要約): Sessile serrated adenomas/polyps (SSA/Ps) are a putative precursor lesion of colon cancer. Although the relevance of DNA hypermethylation in the SSA/P-cancer sequence is well documented, the role of DNA hypomethylation is unknown. We investigated the biological relevance of DNA hypomethylation in the SSA/P-cancer sequence by using 3-dimensional organoids of SSA/P. We first analyzed hypomethylated genes using datasets from our previous DNA methylation array analysis on 7 SSA/P and 2 cancer in SSA/P specimens. Expression levels of hypomethylated genes in SSA/P specimens were determined by RT-PCR and immunohistochemistry. We established 3-dimensional SSA/P organoids and performed knockdown experiments using a lentiviral shRNA vector. DNA hypomethylation at CpG sites of the gene was quantitated by MassARRAY analysis. The mean number of hypomethylated genes in SSA/P and cancer in SSA/P was 41.6 ± 27.5 and 214 ± 19.8, respectively, showing a stepwise increment in hypomethylation during the SSA/P-cancer sequence. S100P, S100α2, PKP3, and MUC2 were most commonly hypomethylated in SSA/P specimens. The mRNA and protein expression levels of S100P, S100α2, and MUC2 were significantly elevated in SSA/P compared with normal colon tissues, as revealed by RT-PCR and immunohistochemistry, respectively. Among these, mRNA and protein levels were highest for S100P. Knockdown of the S100P gene using a lentiviral shRNA vector in 3-dimensional SSA/P organoids inhibited cell growth by >50% (p < 0.01). The mean diameter of SSA/P organoids with S100P gene knockdown was significantly smaller compared with control organoids. MassARRAY analysis of DNA hypomethylation in the S100P gene revealed significant hypomethylation at specific CpG sites in intron 1, exon 1, and the 5'-flanking promoter region. These results suggest that DNA hypomethylation, including S100P hypomethylation, is supposedly associated with the SSA/P-cancer sequence. S100P overexpression via DNA hypomethylation plays an important role in promoting cell growth in the SSA/P-cancer sequence.
(徳島大学機関リポジトリ): ● Metadata: 115966
(出版サイトへのリンク): ● Publication site (DOI): 10.1159/000512575
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 33395688; ● Summary page in Scopus @ Elsevier: 2-s2.0-85099095900

(徳島大学機関リポジトリ: 115966, DOI: 10.1159/000512575, PubMed: 33395688, Elsevier: Scopus) Tomoyuki Kawaguchi, Koichi Okamoto, Shota Fujimoto, Masahiro Bando, Hironori Wada, Hiroshi Miyamoto, Yasushi Sato, Naoki Muguruma, Katsuhisa Horiimoito and Tetsuji Takayama :
Lansoprazole Inhibits the Development of Sessile Serrated Lesions by Inducing G1 Arrest via Skp2/p27 Signaling Pathway.,
Journal of Gastroenterology, Vol.59, No.1, 11-23, 2021.

(要約): Although the serrated-neoplasia pathway reportedly accounts for 15-30% of colorectal cancer (CRC), no studies on chemoprevention of sessile serrated lesions (SSLs) have been reported. We searched for effective compounds comprehensively from a large series of compounds by employing Connectivity Map (CMAP) analysis of SSL-specific gene expression profiles coupled with in vitro screening using SSL patient-derived organoids (PDOs), and validated their efficacy using a xenograft mouse model of SSL. We generated SSL-specific gene signatures based on DNA microarray data, and applied them to CMAP analysis with 1309 FDA-approved compounds to select candidate compounds. We evaluated their inhibitory effects on SSL-PDOs using a cell viability assay. SSL-PDOs were orthotopically transplanted into NOG mice for in vivo evaluation. The signal transduction pathway was evaluated by gene expression profile and protein expression analysis. We identified 221 compounds by employing CMAP analysis of SSL-specific signatures, which should cancel the gene signatures, and narrowed them down to 17 compounds. Cell viability assay using SSL-PDOs identified lansoprazole as having the lowest IC50 value (47 µM) among 17 compounds. When SSL-PDO was orthotopically transplanted into murine intestinal tract, the tumor grew gradually. Administration of lansoprazole to mice inhibited the growth of SSL xenograft whereas the tumor in control mice treated with vehicle alone grew gradually over time. The Ki67 index in xenograft lesions from the lansoprazole group was significantly lower compared with the control group. Cell cycle analysis of SSL-PDOs treated with lansoprazole exhibited a significant increase in G1 phase cell population. Microarray and protein analysis revealed that lansoprazole downregulated Skp2 expression and upregulated p27 expression in SSL-PDOs. Our data strongly suggest that lansoprazole is the most effective chemopreventive agent against SSL, and that lansoprazole induces G1 cell cycle arrest by downregulating Skp2 and upregulating p27 in SSL cells.
(徳島大学機関リポジトリ): ● Metadata: 119258
(出版サイトへのリンク): ● Publication site (DOI): 10.1007/s00535-023-02052-0
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 37989907; ● Search Scopus @ Elsevier (PMID): 37989907; ● Search Scopus @ Elsevier (DOI): 10.1007/s00535-023-02052-0

(徳島大学機関リポジトリ: 119258, DOI: 10.1007/s00535-023-02052-0, PubMed: 37989907) Tamotsu Sagawa, Yasushi Sato, Masahiro Hirakawa, Kyoko Hamaguchi, Akira Fukuya, Koichi Okamoto, Hiroshi Miyamoto, Naoki Muguruma, Koshi Fujikawa, Yasuo Takahashi and Tetsuji Takayama :
Clinical impact of primary tumour location, early tumour shrinkage, and depth of response in the treatment of metastatic colorectal cancer with first-line chemotherapy plus cetuximab or bevacizumab.,
Scientific Reports, Vol.10, No.1, 19815, 2020.

(要約): The primary tumour location is an important prognostic factor for previously untreated metastatic colorectal cancer (mCRC). However, the predictive efficacies of primary tumour location, early tumour shrinkage (ETS), and depth of response (DpR) on mCRC treatment has not been fully evaluated. This study aimed to investigate the predictive efficacies of these traits in mCRC patients treated with first-line 5-fluorouracil-based chemotherapy plus biologic agents, namely, cetuximab and bevacizumab. This was a retrospective analysis of the medical records of 110 patients with pathology-documented unresectable mCRC. Patients with left-sided mCRC receiving any first-line regimen showed better overall survival (OS) than those with right-sided mCRC [33.3 vs 16.3 months; hazard ratio (HR) 0.44; 95% confidence interval (CI) 0.27-0.74; p < 0.001]. In patients with left-sided tumours, treatment with chemotherapy plus cetuximab yielded longer OS than chemotherapy plus bevacizumab (50.6 vs 27.8 months, HR 0.55; 95% CI 0.32-0.97; p = 0.0378). mCRC patients with ETS and high DpR showed better OS than those lacking ETS and with low DpR (33.5 vs 19.6 months, HR 0.50, 95% CI 0.32-0.79, p = 0.023 and 38.3 vs 19.0 months, HR 0.43, 95% CI 0.28-0.68, p < 0.001, respectively). Moreover, ETS and/or high DpR achieved in patients with right-sided mCRC receiving chemotherapy plus cetuximab were associated with significantly better OS than in those lacking ETS and with low DpR (34.3 vs 10.4 months, HR 0.19, 95% CI 0.04-0.94, p = 0.025 and 34.3 vs 10.4 months, HR 0.19, 95% CI 0.04-0.94, p = 0.0257, respectively). Taken together, our study demonstrates that primary tumour location is not only a well-known prognostic factor but also a relevant predictive factor in patients with mCRC receiving chemotherapy plus cetuximab. Additionally, both ETS and DpR could predict treatment outcomes and also potentially guide cetuximab treatment even in right-sided mCRCs.
(徳島大学機関リポジトリ): ● Metadata: 115620
(出版サイトへのリンク): ● Publication site (DOI): 10.1038/s41598-020-76756-1
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 33188279; ● Summary page in Scopus @ Elsevier: 2-s2.0-85095953611

(徳島大学機関リポジトリ: 115620, DOI: 10.1038/s41598-020-76756-1, PubMed: 33188279, Elsevier: Scopus) Jun Okazaki, Toshihito Tanahashi, Yasushi Sato, Jinsei Miyoshi, Tadahiko Nakagawa, Tetsuo Kimura, Hiroshi Miyamoto, Yasuteru Fujino, Fumika Nakamura, Masanori Takehara, beibei ma, Masahiro Bando, Shinji Kitamura, Koichi Okamoto, Naoki Muguruma, Masahiro Sogabe and Tetsuji Takayama :
MicroRNA-296-5p Promotes Cell Invasion and Drug Resistance by Targeting Bcl2-Related Ovarian Killer, Leading to a Poor Prognosis in Pancreatic Cancer.,
Digestion, Vol.101, No.6, 794-806, 2020.

(要約): Pancreatic ductal adenocarcinoma (PDAC) is characterized by aggressive invasion, early metastasis, and resistance to chemotherapy, leading to a poor prognosis. To clarify the molecular mechanism of these malignant characteristics, we performed a genome-wide microRNA (miRNA) array analysis utilizing micro-cancer tissues from patients with unresectable PDAC (stage IV), obtained by endoscopic ultrasound-fine needle aspiration (EUS-FNA). The expression profiles of 2,042 miRNAs were determined using micro-cancer tissues from 13 patients with unresectable PDAC obtained by EUS-FNA. The relationship between individual miRNA levels and overall survival (OS) was analyzed. Possible target genes for miRNAs were bioinformatically analyzed using the online database miRDB. Pancreatic cancer cell lines PANC-1, MIA PaCa-2, and PK-8 were transfected with miRNA mimic or small interfering RNA, and cell invasion, epithelial-mesenchymal transition (EMT), and apoptosis markers were examined. miRNA and mRNA expressions were examined by quantitative polymerase chain reaction. Of 2,042 miRNAs, the 10 that exhibited the lowest correlation coefficient (p 0.005) between miRNA expression level and OS among the patients were identified. The miRDB and expression analysis in cancer cell lines for the 10 miRNAs identified miR-296-5p and miR-1207-5p as biomarkers predictive of shorter survival (p < 0.0005). Bioinformative target gene analysis and transfection experiments with miRNA mimics showed that Bcl2-related ovarian killer (BOK), a pro-apoptotic gene, is a target for miR296-5p in pancreatic cancer cells; transfection of miR-296-5p mimic into PANC-1, MIA PaCa-2, and PK-8 cells resulted in significant suppression of BOK mRNA and protein expression. These transfectants showed significantly higher invasion capability compared with control cells, and knock down of BOK in pancreatic cancer cells similarly enhanced invasion capability. Transfectants of miR-296-5p mimic also exhibited aberrant expression of EMT markers, including vimentin and N-cadherin. Moreover, these transfectants showed a significantly lower apoptosis rate in response to 5-fluorouracil and gemcitabine with a decrease of BOK expression, suggesting a role of miR-296-5p in drug resistance. These results suggest that miR-296-5p is a useful biomarker for a poor prognosis in patients with PDAC, and that the miR-296-5p/BOK signaling axis plays an important role in cell invasion, drug resistance, and EMT in PDACs.
(徳島大学機関リポジトリ): ● Metadata: 114153
(出版サイトへのリンク): ● Publication site (DOI): 10.1159/000503225
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31563901; ● Summary page in Scopus @ Elsevier: 2-s2.0-85072925180

(徳島大学機関リポジトリ: 114153, DOI: 10.1159/000503225, PubMed: 31563901, Elsevier: Scopus) Shota Fuimoto, Naoki Muguruma, Michiyasu Nakao, Hidenori ANDO, Takanori Kashihara, Yoshihiko Miyamoto, Koichi Okamoto, Shigeki Sano, Tatsuhiro Ishida, Yasushi Sato and Tetsuji Takayama :
Indocyanine green-labeled dasatinib as a new fluorescent probe for molecular imaging of gastrointestinal stromal tumors.,
Journal of Gastroenterology and Hepatology, Vol.36, No.5, 1253-1262, 2020.

(要約): It is difficult to differentiate gastrointestinal stromal tumors (GISTs) from other subepithelial lesions under gastrointestinal endoscopy. Because most GISTs express tyrosine kinase receptor c-KIT, fluorescence-labeled c-KIT-specific tyrosine kinase inhibitors seem to be useful agents for molecular imaging of GIST. We aimed to develop a near-infrared fluorescent imaging technology for GIST targeting c-KIT using the novel fluorescent probe indocyanine green-labeled dasatinib (ICG-dasatinib) and to investigate the antitumor effect of ICG-dasatinib on GIST cells. Indocyanine green-labeled dasatinib was synthesized by labeling linker-induced dasatinib with ICG derivative 3-indocyanine-green-acyl-1,3-thiazolidine-2-thione. Human GIST cell lines GIST-T1 and GIST-882M were incubated with ICG-dasatinib and observed by fluorescent microscopy. GIST cells were incubated with ICG-dasatinib, unlabeled dasatinib, or imatinib, and cell viabilities were evaluated. Subcutaneous GIST model mice or orthotopic GIST model rats were intravenously injected with ICG-dasatinib and observed using an IVIS Spectrum. Strong fluorescent signals of ICG-dasatinib were observed in both GIST cell lines in vitro. IC50 values for ICG-dasatinib, unlabeled dasatinib, and imatinib were 13.9, 1.17, and 16.2 nM in GIST-T1 and 26.6, 3.63, and 47.6 nM in GIST-882M cells, respectively. ICG-dasatinib accumulated in subcutaneous xenografts in mice. Fluorescent signals were also observed in liver and gallbladder, indicating biliary excretion; however, fluorescence intensity of tumors was significantly higher than that of intestine after washing. Strong fluorescent signals were observed in orthotopic xenografts through the covering normal mucosa in rats. Indocyanine green-labeled dasatinib could visualize GIST cells and xenografted tumors. The antitumor effect of ICG-dasatinib was preserved to the same degree as imatinib.
(出版サイトへのリンク): ● Publication site (DOI): 10.1111/jgh.15281
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 32989784; ● Search Scopus @ Elsevier (PMID): 32989784; ● Search Scopus @ Elsevier (DOI): 10.1111/jgh.15281

(DOI: 10.1111/jgh.15281, PubMed: 32989784) Tetsu Tomonari, Yasushi Sato, Hironori Tanaka, Takahiro Tanaka, Tatsuya Taniguchi, Masahiro Sogabe, Koichi Okamoto, Hiroshi Miyamoto, Naoki Muguruma, Yu Saitou, Satoru Imura, Yoshimi Bando, Mitsuo Shimada and Tetsuji Takayama :
Conversion therapy for unresectable hepatocellular carcinoma after lenvatinib Three case reports.,
Medicine, Vol.99, No.42, e22782, 2020.

(要約): Lenvatinib (LEN) is a novel potent multi-tyrosine kinase inhibitor, approved as first-line treatment for unresectable hepatocellular carcinoma (HCC). Considering its high objective response rate, LEN therapy could be expected to achieve downstaging of tumors and lead to conversion therapy with hepatectomy or ablation. However, the feasibility of conversion therapy after LEN treatment in unresectable HCC remains largely unknown. Here, we reported 3 cases of unresectable HCC: case 1, a 69-year-old man diagnosed with ruptured HCC; case 2, a 72-year-old woman with nonalcoholic steatohepatitis-based HCC; and case 3, a 73-year-old man with a history of alcoholic cirrhosis-based HCC. In all cases, cirrhosis was classified as Child-Pugh 5 and modified albumin-bilirubin grade 1 or 2a. HCC was diagnosed as Barcelona Clinic Liver Cancer (BCLC) stage B. In all cases, LEN was initiated after conventional-transcatheter arterial embolization enforcement, while maintaining liver function. In all cases, the main tumor size decreased after 6 months of LEN treatment and no satellite nodes were detected, indicating downstaging of HCC to BCLC stage A. Subsequently, conversion hepatectomy or ablation was performed. After successful conversion therapy, the general condition of the patients was good, without tumor recurrence during the observation period (median 10 months). This study demonstrated that LEN enables downstaging of HCC and thus represents a bridge to successful surgery or ablation therapy. In particular, LEN treatment may facilitate the possibility for conversion therapy of initially unresectable HCC, while maintaining the hepatic functional reserve.
(キーワード): Ablation Techniques / Aged / Biomarkers / Carcinoma, Hepatocellular / Female / Hepatectomy / Humans / Liver Neoplasms / Male / Phenylurea Compounds / Protein Kinase Inhibitors / Quinolines / alpha-Fetoproteins
(徳島大学機関リポジトリ): ● Metadata: 116240
(出版サイトへのリンク): ● Publication site (DOI): 10.1097/MD.0000000000022782
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 33080748; ● Search Scopus @ Elsevier (PMID): 33080748; ● Search Scopus @ Elsevier (DOI): 10.1097/MD.0000000000022782

(徳島大学機関リポジトリ: 116240, DOI: 10.1097/MD.0000000000022782, PubMed: 33080748) 藤井祥平, 中村文香, 佐藤康史, 岸和弘, 吉田守美子, 三井康裕, 藤野泰輝, 北村晋志, 岡本耕一, 宮本弘志, 六車直樹, 高山哲治 :
胃癌における免疫チェックポイント阻害薬の効果と免疫関連副作用(irAE) との関連性についての検討,
四国医学雑誌, Vol.76, No.3-4, 173-178, 2020年.

(要約): Recently, immune checkpoint inhibitors(ICI)have been approved for use in advanced gastric cancer(AGC)based on the positive results of ATTRACTION‐2 trial in Japan. There has been accumulating evidence that the development of immune-related adverse events(irAE)may be associated with a response to ICI therapy, particularly in lung cancer, although little is known about these correlations in gastrointestinal cancer. To investigate the efficacy and irAE of ICI treatment and their correlation in AGC, we retrospectively examined 29 patients with AGC who received nivolumab therapy in our departments. Among them, 15 patients(52%)developed irAEs including 4 patients(14%)for grade 3 irAEs ; liver dysfunction(n＝2), type 1 diabetes mellitus(n＝2) and adrenal insufficiency(n＝1). The median overall survival was12．0months in the irAE group and 3．25 months in the non-irAE group(p＝0．164), which suggested the relationship between the effects and irAEs in ICI treatment of AGC. Further research is required to understand the implications of irAE characteristics on ICI response in GCA patients.
(キーワード): Immune-checkpoint inhibitors / Gastric cancer / Immune-related adverse events / Nivolumab
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1050865265018642176

(CiNii: 1050865265018642176) Tetsu Tomonari, Yasushi Sato, Hironori Tanaka, Takahiro Tanaka, Tatsuya Taniguchi, Masahiro Sogabe, Koichi Okamoto, Hiroshi Miyamoto, Naoki Muguruma and Tetsuji Takayama :
Sorafenib as second-line treatment option after failure of lenvatinib in patients with unresectable hepatocellular carcinoma,
JGH Open, Vol.4, No.6, 1135-1139, 2020.

(要約): Abstract Background and Aim Currently, there is no molecular-targeted agent that has demonstrated evidence of efficacy in patients with unresectable hepatocellular carcinoma (u-HCC) who have developed resistance to treatment with lenvatinib (LEN). In this real-world study, we aimed to investigate the therapeutic effect and safety of sorafenib (SOR) in patients with u-HCC after progression on treatment with LEN. Methods (Patients) and Results A total of 13 patients with u-HCC (12 males and 1 female), who were treated with SOR after progression on LEN, were enrolled in this retrospective study. Therapeutic efficacy was evaluated via contrast-enhanced computerized tomography at 8 weeks after the initiation of SOR therapy according to modified response evaluation criteria in solid tumors (mRECIST) and RECIST. According to mRECIST, the objective response rate (ORR) and disease control rate (DCR) were 15.3
(徳島大学機関リポジトリ): ● Metadata: 115923
(出版サイトへのリンク): ● Publication site (DOI): 10.1002/jgh3.12408
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 33319048; ● Summary page in Scopus @ Elsevier: 2-s2.0-85089378719

(徳島大学機関リポジトリ: 115923, DOI: 10.1002/jgh3.12408, PubMed: 33319048, Elsevier: Scopus) Yoshiro Niitsu, Yasushi Sato, Kunihiro Takanashi, Tsuyoshi Hayashi, Naoko Kubo-Birukawa, Fumiko Shimizu, Naoki Fujitani, Rai Shimoyama, Takehiro Kukitsu, Wataru Kurata, Yasuyuki Tashiro and Irving Listowsky :
A CRAF/glutathione-S-transferase P1 complex sustains autocrine growth of cancers with KRAS and BRAF mutations,
Proceedings of the National Academy of Sciences of the United States of America, Vol.117, No.32, 19435-19445, 2020.

(要約): colon cancer. Consequently, hindering the autocrine loop by targeting CRAF/GSTP1 interactions should provide innovative therapeutic modalities for these cancers.
(徳島大学機関リポジトリ): ● Metadata: 116248
(出版サイトへのリンク): ● Publication site (DOI): 10.1073/pnas.2000361117
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 32719131; ● Summary page in Scopus @ Elsevier: 2-s2.0-85089618280

(徳島大学機関リポジトリ: 116248, DOI: 10.1073/pnas.2000361117, PubMed: 32719131, Elsevier: Scopus) Masanori Takehara, Yasushi Sato, Tetsuo Kimura, Kazuyoshi Noda, Hiroshi Miyamoto, Yasuteru Fujino, Jinsei Miyoshi, Fumika Nakamura, Hironori Wada, Yoshimi Bando, Tetsuya Ikemoto, Mitsuo Shimada, Naoki Muguruma and Tetsuji Takayama :
Cancer-associated Adipocytes Promote Pancreatic Cancer Progression Through SAA1 Expression,
Cancer Science, Vol.111, No.8, 2883-2894, 2020.

(要約): Although pancreatic cancer often invades into peripancreatic adipose tissue, little is known about the cancer-adipocyte interaction. We first investigated the ability of adipocytes to de-differentiate to cancer-associated adipocytes (CAAs) by co-culturing with pancreatic cancer cells. We then examined the effects of CAA-conditioned media (CAA-CM) on the malignant characteristics of cancer cells, the mechanism underlying those effects, and their clinical relevance in pancreatic cancer. When 3T3-L1 adipocytes were co-cultured with pancreatic cancer cells (PANC-1) using Transwell system, adipocytes lost their lipid droplets and morphologically changed to fibroblast-like cells (CAA). Adipocyte-specific marker mRNA levels significantly decreased but those of fibroblast-specific markers appeared, characteristic findings of CAA, as revealed by real-time PCR. When PANC-1 cells were cultured with CAA-CM, significantly higher migration/invasion capability, chemoresistance, and epithelial-mesenchymal transition (EMT) properties were observed compared with control cells. To investigate the mechanism underlying these effects, we performed microarray analysis of PANC-1 cells cultured with CAA-CM, and found 78.5-fold higher expression of SAA1 compared with control cells. When SAA1 gene in PANC-1 cells was knocked down with SAA1 siRNA, migration/invasion capability, chemoresistance, and EMT properties were significantly attenuated compared with control cells. Immunohistochemical analysis on human pancreatic cancer tissues revealed positive SAA1 expression in 46/61 (75.4%). Overall survival in the SAA1-positive group was significantly shorter than in the SAA1-negative group (p=0.013). In conclusion, we demonstrated that pancreatic cancer cells induced de-differentiation in adipocytes toward CAA, and CAA promoted malignant characteristics of pancreatic cancer via SAA1 expression, suggesting that SAA1 is a novel therapeutic target in pancreatic cancer.
(徳島大学機関リポジトリ): ● Metadata: 115328
(出版サイトへのリンク): ● Publication site (DOI): 10.1111/cas.14527
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 32535957; ● Summary page in Scopus @ Elsevier: 2-s2.0-85087562532

(徳島大学機関リポジトリ: 115328, DOI: 10.1111/cas.14527, PubMed: 32535957, Elsevier: Scopus) Hironori Tanaka, Koichi Okamoto, Yasushi Sato, Takahiro Tanaka, Tetsu Tomonari, Fumika Nakamura, Yasuteru Fujino, Yasuhiro Mitsui, Hiroshi Miyamoto, Naoki Muguruma, Akinori Morita, Hitoshi Ikushima and Tetsuji Takayama :
Synergistic anti-tumor activity of miriplatin and radiation through PUMA-mediated apoptosis in hepatocellular carcinoma.,
Journal of Gastroenterology, Vol.55, No.11, 1072-1086, 2020.

(要約): The prognosis for patients with unresectable advanced hepatocellular carcinoma (HCC) is poor. Miriplatin is a hydrophobic platinum compound that has a long retention time in lesions after transarterial chemoembolization (TACE). We investigated anti-tumor activity of miriplatin combined with irradiation on HCC cells, and its underlying mechanism of apoptosis. We also analyzed the effectiveness of miriplatin-TACE and radiotherapy for locally advanced HCC. Human HCC cell lines HepG2 and HuH-7 were treated with DPC (active form of miriplatin) and radiation, and synergy was evaluated using a combination index (CI). Apoptosis-related proteins and cell cycles were analyzed by western blotting and flowcytometry. We retrospectively analyzed treatment outcomes in 10 unresectable HCC patients with vascular/bile duct invasion treated with miriplatin-TACE and radiotherapy. DPC or X-ray irradiation decreased cell viability dose-dependently. DPC plus irradiation decreased cell viability synergistically in both cell lines (CI < 1, respectively). Cleaved PARP expression was induced much more strongly by DPC plus irradiation than by each treatment alone. Expression of p53 up-regulated modulator of apoptosis (PUMA) was significantly induced by the combination, and knockdown of PUMA with siRNA significantly decreased apoptosis in both cell lines. DPC plus irradiation caused sub-G1, G2/M, and S phase cell arrest in those cells. The combination of miriplatin-TACE and radiotherapy showed a high response rate for patients with locally advanced HCC despite small number of patients. Miriplatin plus irradiation had synergistic anti-tumor activity on HCC cells through PUMA-mediated apoptosis and cell cycle arrest. This combination may possibly be effective in treating locally advanced HCC.
(徳島大学機関リポジトリ): ● Metadata: 115325
(出版サイトへのリンク): ● Publication site (DOI): 10.1007/s00535-020-01705-8
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 32666201; ● Summary page in Scopus @ Elsevier: 2-s2.0-85087895196

(徳島大学機関リポジトリ: 115325, DOI: 10.1007/s00535-020-01705-8, PubMed: 32666201, Elsevier: Scopus) Tetsu Tomonari, Yasushi Sato, Hironori Tanaka, Takahiro Tanaka, Yasuteru Fujino, Yasuhiro Mitsui, Akihiro Hirao, Tatsuya Taniguchi, Koichi Okamoto, Masahiro Sogabe, Hiroshi Miyamoto, Naoki Muguruma, Harumi Kagiwada, Masashi Kitazawa, Kazuhiro Fukui, Ktsuhisa Horimoto and Tetsuji Takayama :
Potential use of lenvatinib for patients with unresectable hepatocellular carcinoma including after treatment with sorafenib: Real-world evidence and in vitro assessment via protein phosphorylation array.,
Oncotarget, Vol.11, No.26, 2531-2542, 2020.

(要約): The efficacy and safety of lenvatinib (LEN) as a second/third-line treatment for unresectable hepatocellular carcinoma (HCC) after sorafenib (SOR) therapy remains unknown. We evaluated the outcomes of second/third-line LEN treatment, investigated the sensitivity of a SOR-resistant HCC cell line (PLC/PRF5-R2) to LEN, and assessed their signal transduction pathways by protein array analysis. We retrospectively enrolled 57 patients with unresectable HCC. Fifty-three radiologically evaluated patients comprised 34 molecular-targeted agent (MTA)-naive (first-line), nine intolerant to SOR (second-line), and 10 resistant to regorafenib (third-line). The objective response rates (ORRs) were 61.8% in first-line, 33.3% in second-line, and 20.0% in third-line groups. The overall survival (OS) in the first-line was significantly longer than that in the third-line group ( < 0.05). Patients with better liver functional reserves (child score, ALBI grade) exhibited higher ORR and longer OS. The IC of LEN against PLC/PRF5-R2 was significantly higher than that against PLC/PRF5. LEN significantly inhibited more LEN-related signal transduction pathways in PLC/PRF5 than in PLC/PRF5-R2 cells. This suggests that LEN is active and safe as a second/third-line treatment for unresectable HCC. LEN seems more effective for patients with HCC with better hepatic reserve functions or before MTA-resistance is acquired because of the partial cross-resistance to SOR.
(徳島大学機関リポジトリ): ● Metadata: 116246
(出版サイトへのリンク): ● Publication site (DOI): 10.18632/oncotarget.27640
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 32655838; ● Search Scopus @ Elsevier (PMID): 32655838; ● Search Scopus @ Elsevier (DOI): 10.18632/oncotarget.27640

(徳島大学機関リポジトリ: 116246, DOI: 10.18632/oncotarget.27640, PubMed: 32655838) Tadahiko Nakagawa, Yasushi Sato, Toshihito Tanahashi, Yasuhiro Mitsui, Yoshifumi Kida, Yasuteru Fujino, Misato Hirata, Shinji Kitamura, Hiroshi Miyamoto, Koichi Okamoto, Naoki Muguruma, Yoshimi Bando and Tetsuji Takayama :
JMJD2A sensitizes gastric cancer to chemotherapy by cooperating with CCDC8.,
Gastric Cancer, Vol.23, No.3, 426-436, 2020.

(要約): Jumonji domain-containing protein 2A (JMJD2A) of the JMJD2 family of histone lysine demethylases has been implicated in tumorigenesis. However, its expression and role in gastric cancer (GC) drug resistance remain unknown. Here, we investigated the role of JMJD2A in GC chemotherapeutic susceptibility and its clinical relevance in GC. We selected 12 relevant genes from previously identified gene signatures that can predict GC susceptibility to docetaxel, cisplatin, and S-1 (DCS) therapy. Each gene was knocked down using siRNA in GC cell lines, and cell viability assays were performed. JMJD2A expression in GC cell lines and tissues was assessed using qRT-PCR and immunohistochemistry, respectively. A JMJD2A downstream target related to drug susceptibility was examined using whole-gene expression array and immunoprecipitation. Among the 12 candidate genes, down-regulation of JMJD2A showed the maximum effect on GC susceptibility to anti-cancer drugs and increased the IC values for 5-FU, cisplatin, and docetaxel 15.3-, 2.7-, and 4.0-fold, respectively. JMJD2A was universally expressed in 12 GC cell lines, and its overexpression in GC tissue was positively correlated with tumor regression in 34 DCS-treated patients. A whole-gene expression array of JMJD2A-knockdown GC cells demonstrated a significant decrease in the expression of pro-apoptotic coiled-coil domain containing 8 (CCDC8), a downstream target of JMJD2A. Direct interaction between CCDC8 and JMJD2A was verified using immunoprecipitation. CCDC8 inhibition restored drug resistance to docetaxel, cisplatin, and S-1. Our results indicate that JMJD2A is a novel epigenetic factor affecting GC chemotherapeutic susceptibility, and JMJD2A/CCDC8 is a potential GC therapeutic target.
(出版サイトへのリンク): ● Publication site (DOI): 10.1007/s10120-019-01024-9
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31677131; ● Summary page in Scopus @ Elsevier: 2-s2.0-85074813194

(DOI: 10.1007/s10120-019-01024-9, PubMed: 31677131, Elsevier: Scopus) Yoshihiko Miyamoto, Naoki Muguruma, Shota Fujimoto, Yasuyuki Okada, Yoshifumi Kida, Fumika Nakamura, Kumiko Tanaka, Tadahiko Nakagawa, Shinji Kitamura, Koichi Okamoto, Hiroshi Miyamoto, Yasushi Sato and Tetsuji Takayama :
Epidermal growth factor receptortargeted molecular imaging of colorectal tumors: Detection and treatment evaluation of tumors in animal models.,
Cancer Science, Vol.110, No.6, 1921-1930, 2019.

(要約): To overcome the problem of overlooking colorectal tumors, a new and highly sensitive modality of colonoscopy is needed. Moreover, it is also important to establish a new modality to evaluate viable tumor volume in primary lesions of colorectal cancer (CRC) during chemotherapy. Therefore, we carried out molecular imaging of colorectal tumors targeting epidermal growth factor receptor (EGFR), which is highly expressed on tumor cells, for evaluating chemotherapeutic efficacy and for endoscopic detection of colorectal adenomas. We first attempted to image five CRC cell lines with various levels of EGFR expression using an Alexa Fluor-labeled anti-EGFR monoclonal antibody (AF-EGFR-Ab). A strong fluorescence signal was observed in the cells depending on the level of EGFR expression. When nude mice xenografted with LIM1215 CRC cells, which highly express EGFR, were i.v. injected with AF-EGFR-Ab, a strong fluorescence signal appeared in the tumor with a high signal to noise ratio, peaking at 48 hours after injection and then gradually decreasing, as shown using an IVIS Spectrum system. When the xenografted mice were treated with 5-fluorouracil, fluorescence intensity in the tumor decreased in proportion to the viable tumor cell volume. Moreover, when the colorectum of azoxymethane-treated rats was observed using a thin fluorescent endoscope with AF-EGFR-Ab, all 10 small colorectal adenomas (3 mm) were detected with a clear fluorescence signal. These preliminary results of animal experiments suggest that EGFR-targeted fluorescent molecular imaging may be useful for quantitatively evaluating cell viability in CRC during chemotherapy, and also for detecting small adenomas using a fluorescent endoscope.
(キーワード): Animals / Antineoplastic Agents / Azoxymethane / Cell Line, Tumor / Cell Survival / Colorectal Neoplasms / ErbB Receptors / 女性 (female) / Fluorouracil / HT29 Cells / Humans / 男性 (male) / Mice, Inbred BALB C / Mice, Nude / Molecular Targeted Therapy / Rats, Inbred F344 / Xenograft Model Antitumor Assays
(徳島大学機関リポジトリ): ● Metadata: 113790
(出版サイトへのリンク): ● Publication site (DOI): 10.1111/cas.14020
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 30973663; ● Summary page in Scopus @ Elsevier: 2-s2.0-85066789077

(徳島大学機関リポジトリ: 113790, DOI: 10.1111/cas.14020, PubMed: 30973663, Elsevier: Scopus) Yasushi Sato, Tamotsu Sagawa, Hiroyuki Ohnuma, Masahiro Hiarakawa, Yasuo Takahashi, Kyoko Hamaguchi, Koshi Fujikawa, Takayuki Nobuoka, Koichi Okamoto, Hiroshi Miyamoto, Naoki Muguruma, Ichiro Takemasa and Tetsuji Takayama :
A dose-escalation study of docetaxel, oxaliplatin, and S-1 (DOS) as a first-line therapy for patients with unresectable metastatic gastric cancer.,
Cancer Chemotherapy and Pharmacology, Vol.83, No.1, 161-167, 2019.

(要約): The aim of this study was to determine the recommended dose (RD) for a docetaxel/oxaliplatin/S-1 (DOS) regimen in patients with unresectable gastric cancer and to preliminarily evaluate its efficacy. Previously untreated patients with histologically proven unresectable metastatic gastric cancer were enrolled (n = 16). Docetaxel and oxaliplatin were administered intravenously on day 8 and S-1 was administered orally twice a day on days 1-14. Each cycle was repeated every 3 weeks. Dose-limiting toxicities (DLTs) were evaluated during the first treatment cycle. Three dose escalations of DOS were employed in this study: level 1 (50/100/80 mg/m), level 2 (50/130/80 mg/m), and level 3 (60/130/80 mg/m). According to the 3 + 3 dose-escalating schedule, we determined that the RD and maximum tolerated dose for this regimen were level 1 and level 2, respectively. The DLTs were grade 3 diarrhea and febrile neutropenia. The overall response rate was 78% (7/9) for patients with measurable lesions and consisted of two complete responses and five partial responses. Five patients underwent conversion surgery. The median follow-up time was 19 months with median survival time and progression-free survival being 19.6 months and 7.6 months, respectively. The results from this study demonstrated the safety and tolerability of DOS in unresectable metastatic gastric cancer patients and revealed promising preliminary efficacy with a high conversion rate. A phase II trial of DOS regimen using the identified RD is ongoing.
(出版サイトへのリンク): ● Publication site (DOI): 10.1007/s00280-018-3719-0
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 30406285; ● Search Scopus @ Elsevier (PMID): 30406285; ● Search Scopus @ Elsevier (DOI): 10.1007/s00280-018-3719-0

(DOI: 10.1007/s00280-018-3719-0, PubMed: 30406285) Hiroyuki Ohnuma, Yasushi Sato, Naotaka Hayasaka, Teppei Matsuno, Chisa Fujita, Masanori Sato, Takahiro Osuga, Masahiro Hirakawa, Koji Miyanishi, Tamotsu Sagawa, Koshi Fujikawa, Motoh Ohi, Yutaka Okagawa, Yasushi Tsuji, Michiaki Hirayama, Tatsuya Ito, Takayuki Nobuoka, Ichiro Takemasa, Masayoshi Kobune and Junji Kato :
Neoadjuvant chemotherapy with docetaxel, nedaplatin and fluorouracil for resectable esophageal cancer: A phase II study.,
Cancer Science, 2018.

(要約): /day) on days 1-5 and 8-12, every three weeks. After three courses of chemotherapy, esophagectomy was performed. The primary endpoint was the completion rate of the protocol treatment. Twenty-eight patients were enrolled (cStage Ib/II/III: 2/3/23) and all received at least two cycles of chemotherapy. Twenty-five patients underwent surgery, all of whom achieved an R0 resection, leading to a completion rate of 89.3%. The overall response rate was 87.0%. A pathological complete response was confirmed in eight (32.0%) cases. Grade 3/4 adverse events included leukopenia (32.1%), neutropenia (39.3%), febrile neutropenia (10.7%), thrombocytopenia (10.7%), and diarrhea (14.3%), but were manageable. Treatment-related deaths and major surgical complications did not occur. Estimated two-year progression-free and overall survival rates were 70.4% and 77.2%, respectively. Thus, DNF therapy was well tolerated, and deemed feasible, with a strong tumor response in a neoadjuvant setting for ESCC. This trial is registered with the University Hospital Medical Information Network (UMIN ID: 000014305). This article is protected by copyright. All rights reserved.
(徳島大学機関リポジトリ): ● Metadata: 114570
(出版サイトへのリンク): ● Publication site (DOI): 10.1111/cas.13772
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 30137686; ● Summary page in Scopus @ Elsevier: 2-s2.0-85053774570

(徳島大学機関リポジトリ: 114570, DOI: 10.1111/cas.13772, PubMed: 30137686, Elsevier: Scopus) Kaizo Kagemoto, Koichi Okamoto, Tohshi Takaoka, Yasushi Sato, Shinji Kitamura, Tetsuo Kimura, Masahiro Sogabe, Hiroshi Miyamoto, Naoki Muguruma, Koichi Tsuneyama and Tetsuji Takayama :
Detection of aberrant crypt foci with image-enhanced endoscopy.,
Endoscopy International Open, Vol.6, No.8, E924-E933, 2018.

(要約): Conventional detection of aberrant crypt foci (ACF) with dye-spraying and magnifying observation is labor- and skill-intensive. We performed a prospective non-inferiority study to investigate the utility of image-enhanced endoscopy (IEE) for detection of ACF. Patients with a history of colorectal neoplasm were eligible. The number of ACF in the lower rectum was counted first using IEE magnification with narrow-band imaging (NBI) or blue-laser imaging (BLI), and subsequently using the methylene blue method. The primary endpoint was the ACF detection rate with IEE, i. e., the number of ACF detected with IEE relative to the number of ACF detected with methylene blue. The secondary endpoints were bowel preparation time, ACF detection time, and the detection rate with NBI or BLI. A total of 40 patients were enrolled (NBI 20 and BLI 20). The overall detection rate for ACF with IEE was 81.7 % (503/616; 95 %CI 78.8 - 84.6 %), meeting the primary endpoint. The detection rate for ACF with BLI (84.9 %, 258/304) was significantly higher than with NBI (78.5 %, 245/312; < 0.05). Both bowel preparation time and ACF detection time were significantly shorter with IEE versus the methylene blue method ( < 0.01, respectively). The detection rates for dysplastic and non-dysplastic ACF with IEE were 84.4 % (27/32) and 80.3 % (469/584), respectively. IEE is able to detect ACF during colonoscopy with sensitivity non-inferior to that of the conventional methylene blue method. IEE is simpler than the methylene blue method and is therefore a potentially useful new tool for ACF detection.
(徳島大学機関リポジトリ): ● Metadata: 112032
(出版サイトへのリンク): ● Publication site (DOI): 10.1055/a-0621-8794
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 30123821; ● Search Scopus @ Elsevier (PMID): 30123821; ● Search Scopus @ Elsevier (DOI): 10.1055/a-0621-8794

(徳島大学機関リポジトリ: 112032, DOI: 10.1055/a-0621-8794, PubMed: 30123821) Shota Fujimoto, Naoki Muguruma, Koichi Okamoto, Takeshi Kurihara, Yasushi Sato, Yoshihiko Miyamoto, Shinji Kitamura, Hiroshi Miyamoto, Takahiro Taguchi, Koichi Tsuneyama and Tetsuji Takayama :
A Novel Theranostic Combination of Near-infrared Fluorescence Imaging and Laser Irradiation Targeting c-KIT for Gastrointestinal Stromal Tumors.,
Theranostics, Vol.8, No.9, 2313-2328, 2018.

(要約): It is difficult to distinguish gastrointestinal stromal tumors (GISTs) from other types of submucosal tumors under conventional gastrointestinal endoscopy. We aimed to detect GISTs by molecular fluorescence imaging using a near-infrared (NIR) photosensitizer (IR700)-conjugated anti-c-KIT antibody and to treat GISTs by photoimmunotherapy with NIR irradiation as a non-invasive theranostic procedure. We also investigated the therapeutic mechanisms. Human GIST cell lines GIST-T1 and GIST-882M were incubated with IR700-conjugated anti-c-KIT antibody, IR700-12A8, and observed by confocal laser microscopy. Mice with GIST-T1 xenografts or rats with orthotopic xenografts were injected with IR700-12A8 or AF488-conjugated antibody, and observed under IVIS or autofluorescence imaging (AFI) endoscopy. GIST cells were treated with IR700-12A8 and NIR light and vivo, and cell viability, histology and apoptosis were evaluated. Strong red fluorescence of IR700-12A8 was observed on the cell membrane of GIST cells and was gradually internalized into the cytoplasm. Tumor-specific accumulation of IR700-12A8 was observed in GIST-T1 xenografts in mice. Under AFI endoscopy, a strong fluorescence signal was observed in orthotopic GIST xenografts in rats through the normal mucosa covering the tumor. The percentage of dead cells significantly increased in a light-dose-dependent manner and both acute necrotic and late apoptotic cell death was observed with annexin/PI staining. Cleaved PARP expression was significantly increased after IR700-12A8-mediated NIR irradiation, which was almost completely reversed by NaN. All xenograft tumors (7/7) immediately regressed and 4/7 tumors completely disappeared after IR700-12A8-mediated NIR irradiation. Histologic assessment and TUNEL staining revealed apoptosis in the tumors. NIR fluorescence imaging using IR700-12A8 and subsequent NIR irradiation could be a very effective theranostic technology for GIST, the underlying mechanism of which appears to involve acute necrosis and supposedly late apoptosis induced by singlet oxygen.
(徳島大学機関リポジトリ): ● Metadata: 111436
(出版サイトへのリンク): ● Publication site (DOI): 10.7150/thno.22027
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29721082; ● Summary page in Scopus @ Elsevier: 2-s2.0-85044356978

(徳島大学機関リポジトリ: 111436, DOI: 10.7150/thno.22027, PubMed: 29721082, Elsevier: Scopus) Hiroyuki Ohnuma, Yasushi Sato, Masahiro Hirakawa, Shohei Kikuchi, Koji Miyanishi, Tamotsu Sagawa, Yasuo Takahashi, Takayuki Nobuoka, Koichi Okamoto, Hiroshi Miyamoto, Ichiro Takemasa, Tetsuji Takayama and Junji Kato :
Docetaxel, cisplatin and S-1 (DCS) combination chemotherapy for gastric cancer patients with peritoneal metastasis: a retrospective study.,
Cancer Chemotherapy and Pharmacology, Vol.81, No.3, 539-548, 2018.

(要約): ) and docetaxel (50-60 mg/m
(出版サイトへのリンク): ● Publication site (DOI): 10.1007/s00280-018-3523-x
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29383482; ● Search Scopus @ Elsevier (PMID): 29383482; ● Search Scopus @ Elsevier (DOI): 10.1007/s00280-018-3523-x

(DOI: 10.1007/s00280-018-3523-x, PubMed: 29383482) Rie Harada, Masako Kimura, Yasushi Sato, Tatsuya Taniguchi, Tetsu Tomonari, Takahiro Tanaka, Hironori Tanaka, Naoki Muguruma, Hirohiko Shinomiya, Hirohito Honda, Issei Imoto, Masahiro Sogabe, Toshiya Okahisa and Tetsuji Takayama :
APOB codon 4311 polymorphism is associated with hepatitis C virus infection through altered lipid metabolism.,
BMC Gastroenterology, Vol.18, No.1, 24, 2018.

(要約): It has been reported that some single-nucleotide polymorphisms (SNPs) in lipid regulators such as apolipoproteins and cell surface molecules for hepatitis C virus (HCV) entry into hepatocytes are associated with HCV infection. However, it is unknown how HCV infection is affected by altered lipid metabolism resulting from the SNPs. We investigated the relationship between these SNPs and HCV infection status, and also analyzed the mechanism by which these SNPs mediate HCV infection via lipid metabolism alterations. Serum lipid and apolipoprotein profiles were tested in 158 HCV-positive and 220 HCV-negative subjects. We selected 22 SNPs in five lipid regulator genes which were related to HCV entry into hepatocytes and to lipid metabolism (APOA1, APOB, SR-B1, LDLR, and APOE), and their polymorphisms were analyzed using the PCR-sequence-specific oligonucleotide probe-Luminex method. An APOB N4311S (g.41553a > g) SNP, rs1042034, was significantly associated with HCV positivity; the HCV positivity rate for the minor allele AA genotype was significantly higher than for genotype AG + GG (P = 0.016). Other SNPs except for APOB P2712L SNP rs676210, which is in linkage disequilibrium with rs1042034, showed no significant difference in genotype distribution. The serum level of low density lipoprotein-cholesterol (LDL-C) in the genotype AA group was significantly lower than in the genotype non-AA group (P = 0.032), whereas the triglyceride (TG) level was significantly higher (P = 0.007). An APOB SNP, rs1042034, is closely associated with HCV infection through lipid metabolism alteration. The minor allele AA genotype might contribute to facilitating serum LDL uptake into hepatocytes via LDLR by modifying their affinity and interaction and may have an influence on HCV infection by their entry to the liver through the LDLR.
(徳島大学機関リポジトリ): ● Metadata: 111808
(出版サイトへのリンク): ● Publication site (DOI): 10.1186/s12876-018-0747-5
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29382324; ● Summary page in Scopus @ Elsevier: 2-s2.0-85041353404

(徳島大学機関リポジトリ: 111808, DOI: 10.1186/s12876-018-0747-5, PubMed: 29382324, Elsevier: Scopus) Yasushi Sato, Masahiro Hirakawa, Hiroyuki Ohnuma, Minoru Takahashi, Tetsuro Okamoto, Koichi Okamoto, Hiroshi Miyamoto, Naoki Muguruma, Tomohisa Furuhata, Ichiro Takemasa, Junji Kato and Tetsuji Takayama :
A triplet combination with capecitabine/oxaliplatin/irinotecan (XELOXIRI) plus cetuximab as first-line therapy for patients with metastatic colorectal cancer: a dose escalation study.,
Cancer Chemotherapy and Pharmacology, Vol.80, No.6, 1133-1139, 2017.

(要約): The addition of cetuximab to triplet chemotherapy can increase treatment efficacy for patients with metastatic colorectal cancer (mCRC). We explored the dose-limiting toxicity and feasibility of a triweekly capecitabine, oxaliplatin, irinotecan, plus cetuximab (XELOXIRI plus cetuximab) regimen in patients with wild-type KRAS mCRC. Patients received oxaliplatin (100 mg/m, day 1), capecitabine (1700 mg/m per day from day 2 to 15), irinotecan (100, 120, and 150 mg/m for dose levels 1, 2, 3, respectively, on day 1), and cetuximab (400 mg/m, day 1 and, thereafter, 250 mg/m every week), repeated every 3 weeks. Dose-limiting toxicities (DLTs) were assessed in the first 2 treatment cycles to determine the maximum tolerated dose (MTD) and the recommended dose (RD). Twelve patients received a median of 7 cycles of therapy (range 2-10). The DLT was grade 4 neutropenia, observed in 1 of 6 patients at dose level 2. The MTD was not reached at dose level 3. Therefore, the RD of irinotecan was defined as 150 mg/m. Most common grade ≥ 3 toxicities were neutropenia (50%), diarrhea (17%), and febrile neutropenia (8%). The response rate was 83% (complete and partial response: 1 and 9 patient(s), respectively), including 4 conversion cases. The combination of XELOXIRI and cetuximab is feasible and has an acceptable toxicity profile; neutropenia was the DLT. The RD of irinotecan is 150 mg/m. The observed response rate was promising and warrants further investigation.
(キーワード): Adult / Aged / Antimetabolites, Antineoplastic / Antineoplastic Combined Chemotherapy Protocols / Camptothecin / Capecitabine / Cetuximab / Colorectal Neoplasms / Female / Humans / Male / Middle Aged / Neoplasm Metastasis / Organoplatinum Compounds
(出版サイトへのリンク): ● Publication site (DOI): 10.1007/s00280-017-3458-7
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29038850; ● Summary page in Scopus @ Elsevier: 2-s2.0-85031928685

(DOI: 10.1007/s00280-017-3458-7, PubMed: 29038850, Elsevier: Scopus) Naoki Uemura, Shohei Kikuchi, Yasushi Sato, Hiroyuki Ohnuma, Koichi Okamoto, Hiroshi Miyamoto, Masahiro Hirakawa, Tamotsu Sagawa, Koshi Fujikawa, Yasuo Takahashi, Toshinori Okuda, Shinya Minami, Minoru Takahashi, Tetsuro Okamoto, Kohichi Takada, Koji Miyanisi, Tetsuji Takayama and Junji Kato :
A phase II study of modified docetaxel, cisplatin, and S-1 (mDCS) chemotherapy for unresectable advanced gastric cancer.,
Cancer Chemotherapy and Pharmacology, Vol.80, No.4, 707-713, 2017.

(要約): Forty-nine patients were enrolled from November 2011 to April 2014, and 43 were eligible. The overall RR was 79.1%, including two cases of a complete response (4.7%), and 32 cases of a partial response (74.4%). Nine cases had stable disease (20.9%) but none showed progressive disease. Of the 43 cases, 15 cases (34.9%) underwent curative conversion surgery. The median PFS was 350 days (95% CI 240-416 days) and median OS was 722 days (95% CI 411 days-not reached). Grade 3/4 neutropenia developed in 79.1%, and febrile neutropenia in 34.9%, of patients. Non-hematological grade 3/4 adverse events were anorexia (25.6%), nausea (4.7%), and diarrhea (9.3%).
(出版サイトへのリンク): ● Publication site (DOI): 10.1007/s00280-017-3404-8
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28849257; ● Search Scopus @ Elsevier (PMID): 28849257; ● Search Scopus @ Elsevier (DOI): 10.1007/s00280-017-3404-8

(DOI: 10.1007/s00280-017-3404-8, PubMed: 28849257) Shogo Miura, Kazuyuki Murase, Akira Sakurada, Kohichi Takada, Satoshi Iyama, Tsutomu Sato, 佐藤康史, Koji Miyanishi, Masayoshi Kobune, Atsuko Muranaka, Kazutoshi Tachibana, Junji Kato :
[A Case of Chronic Myelogenous Leukemia That Developed Fibrous Pericarditis Owing to Nilotinib Use].,
癌と化学療法, Vol.44, No.6, 529-531, 2017年.

(要約): A 64-year-old man was diagnosed with chronic-phase chronic myelogenous leukemia(CML)in May 2009. He was treated with imatinib and achieved complete cytogenetic response(CCyR)in 2 months. After 4 months of treatment, he developed interstitial pneumonia and became intolerant to imatinib. He was then switched to nilotinib from October of the same year. In June 2013, he was diagnosed with drug-induced pericarditis resulting from nilotinib use, and thus, nilotinib was discontinued. Subsequently, he was followed up without specific treatment for CML. In January 2014, he was admitted to the Dept. of Cardiovascular, Renal and Metabolic Medicine at our hospital because of heart failure. After examinations of cardiac function, he was diagnosed with constrictive pericarditis. Therefore, pericardiolysis was performed by the Dept. of Cardiovascular Surgery at our hospital. Pathologic findings showed hyaline-like fibrous tissue proliferation in the pericardium, which was diagnosed as fibrous pericarditis induced by nilotinib. We report a case of chronic myelogenous leukemia that developed fibrous pericarditis owing to nilotinib use.
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28698448; ● Search Scopus @ Elsevier (PMID): 28698448

(PubMed: 28698448) Yasushi Sato, Hiroyuki Ohnuma, Takayuki Nobuoka, Masahiro Hirakawa, Tamotsu Sagawa, Koshi Fujikawa, Yasuo Takahashi, Shinya Minami, Shinichi Katsuki, Minoru Takahashi, Masahiro Maeda, Yutaka Okagawa, Naoki Uemura, Syouhei Kikuch, Koichi Okamoto, Hiroshi Miyamoto, Mitsuo Shimada, Ichiro Takemasa, Junji Kato and Tetsuji Takayama :
Conversion therapy for inoperable advanced gastric cancer patients by docetaxel, cisplatin, and S-1 (DCS) chemotherapy: a multi-institutional retrospective study.,
Gastric Cancer, Vol.20, No.3, 517-526, 2017.

(要約): Conversion therapy is an option for unresectable metastatic gastric cancer when distant metastases are controlled by chemotherapy; however, the feasibility and efficacy remain unclear. This study aimed to assess the feasibility and efficacy of conversion therapy in patients with initially unresectable gastric cancer treated with docetaxel, cisplatin, and S-1 (DCS) chemotherapy by evaluating clinical outcomes. One hundred unresectable metastatic gastric cancer patients, enrolled in three DCS chemotherapy clinical trials, were retrospectively evaluated. The patients received oral S-1 (40 mg/m2 b.i.d.) on days 1-14 and intravenous cisplatin (60 mg/m2) and docetaxel (50-60 mg/m2) on day 8 every 3 weeks. Conversion therapy was defined when the patients could undergo R0 resection post-DCS chemotherapy and were able to tolerate curative surgery. Conversion therapy was achieved in 33/100 patients, with no perioperative mortality. Twenty-eight of the 33 patients (84.8 %) achieved R0 resection, and 78.8 % were defined as histological chemotherapeutic responders. The median overall survival (OS) of patients who underwent conversion therapy was 47.8 months (95 % CI 28.0-88.5 months). Patients who underwent R0 resection had significantly longer OS than those who underwent R1 and R2 resections (P = 0.0002). Of the patients with primarily unresectable metastases, 10 % lived >5 years. Among patients who underwent conversion therapy, multivariate analysis showed that the pathological response was a significant independent predictor for OS. DCS safely induced a high conversion rate, with very high R0 and pathological response rates, and was associated with a good prognosis; these findings warrant further prospective investigations.
(キーワード): Administration, Oral / Adult / Aged / Antineoplastic Combined Chemotherapy Protocols / Cisplatin / Drug Combinations / Female / Humans / Male / Middle Aged / Oxonic Acid / Postoperative Care / Prognosis / Retrospective Studies / Stomach Neoplasms / Survival Analysis / Taxoids / Tegafur / Treatment Outcome
(出版サイトへのリンク): ● Publication site (DOI): 10.1007/s10120-016-0633-1
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27553665; ● Summary page in Scopus @ Elsevier: 2-s2.0-84983383466

(DOI: 10.1007/s10120-016-0633-1, PubMed: 27553665, Elsevier: Scopus) Hiroyuki Ohnuma, Kazuma Ishikawa, Masahiro Hirakawa, Shohei Kikuchi, Yasushi Sato, Koji Miyanishi and Junji Kato :
Cases of primary malignant melanoma and melanocytosis of the esophagus observed by magnifying endoscopy: Application to differential diagnosis: case series.,
Medicine, Vol.96, No.17, e6701, 2017.

(要約): Primary malignant melanoma of the esophagus (PMME) is a rare disease with an extremely poor prognosis. In contrast, melanocytosis is a benign condition defined as melanocytic proliferation with melanin deposition. PMME is often accompanied by melanocytosis, but differentiating between them is difficult because of their similar appearance. Here, we reported 3 PMME cases, 2 with melanocytosis. Magnifying endoscopy revealed characteristic non-uniform pigmented spots along deformed intrapapillary capillary loops (IPCLs) in PMME, while melanocytosis showed fine granule-like or linearly arranged spots and intact IPCLs. The patients underwent endoscopic or surgical resection of each lesion. Histologically, magnified images reflected melanocyte growth. For cases 1 and 2, the patients remained disease-free for 61 and 15 months after endoscopic resection, respectively. In case 3, liver metastases developed two months after surgery, and the patient died from liver failure after six months. This is the first report describing differences in magnified views of the 2 diseases, which aids a differential diagnosis.
(キーワード): Aged / Aged, 80 and over / Diagnosis, Differential / Esophageal Neoplasms / Esophagoscopy / Esophagus / Humans / Male / Melanoma / Natural Orifice Endoscopic Surgery / Pigmentation Disorders
(徳島大学機関リポジトリ): ● Metadata: 115593
(出版サイトへのリンク): ● Publication site (DOI): 10.1097/MD.0000000000006701
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28445275; ● Search Scopus @ Elsevier (PMID): 28445275; ● Search Scopus @ Elsevier (DOI): 10.1097/MD.0000000000006701

(徳島大学機関リポジトリ: 115593, DOI: 10.1097/MD.0000000000006701, PubMed: 28445275) Shigenori Ota, Miyuki Nishimura, Yuya Murakami, Kubo Naoko Birukawa, Akihiro Yoneda, Hiroki Nishita, Ryosuke Fujita, Yasushi Sato, Kenjiro Minomi, Keiko Kajiwara, Miyono Miyazaki, Maki Uchiumi, Shintaro Mikuni, Yasuaki Tamura, Toru Mizuguchi, Masafumi Imamura, Makoto Meguro, Yasutoshi Kimura, Koichi Hirata and Yoshiro Niitsu :
Involvement of Pancreatic Stellate Cells in Regeneration of Remnant Pancreas after Partial Pancreatectomy.,
PLoS ONE, Vol.11, No.12, 142-149, 2016.

(要約): aPSCs play a crucial role in regeneration of remnant pancreas, proliferation of acinar and islet cells after PX through the activity of secreted collagen. Characterization of new area emerged by siRNA HSP47 treatment as to its origin is a future task.
(キーワード): Acute Disease / Adult / Female / Humans / Insulin-Secreting Cells / Kinetics / Male / Pancreas / Pancreatectomy / Pancreatic Neoplasms / Pancreatitis / Regeneration / Retrospective Studies / Tomography, X-Ray Computed
(徳島大学機関リポジトリ): ● Metadata: 112310
(出版サイトへのリンク): ● Publication site (DOI): 10.1371/journal.pone.0165747
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27935983; ● Summary page in Scopus @ Elsevier: 2-s2.0-85005991794

(徳島大学機関リポジトリ: 112310, DOI: 10.1371/journal.pone.0165747, PubMed: 27935983, Elsevier: Scopus) Yusuke Kamihara, Kohichi Takada, Tsutomu Sato, Yutaka Kawano, Kazuyuki Murase, Yohei Arihara, Shohei Kikuchi, Naotaka Hayasaka, Makoto Usami, Satoshi Iyama, Koji Miyanishi, Yasushi Sato, Masayoshi Kobune and Junji Kato :
The iron chelator deferasirox induces apoptosis by targeting oncogenic Pyk2/-catenin signaling in human multiple myeloma.,
Oncotarget, Vol.7, No.39, 64330-64341, 2016.

(要約): Deregulated iron metabolism underlies the pathogenesis of many human cancers. Recently, low expression of ferroportin, which is the only identified non-heme iron exporter, has been associated with significantly reduced overall survival in multiple myeloma (MM); however, the altered iron metabolism in MM biology remains unclear. In this study we demonstrated, by live cell imaging, that MM cells have increased intracellular iron levels as compared with normal cells. In experiments to test the effect of iron chelation on the growth of MM cells, we found that deferasirox (DFX), an oral iron chelator used to treat iron overload in clinical practice, inhibits MM cell growth both in vivo and in vitro. Mechanistically, DFX was found to induce apoptosis of MM cells via the inhibition of proline-rich tyrosine kinase 2 (Pyk2), which is known to promote tumor growth in MM. Inhibition of Pyk2 is caused by the suppression of reactive oxygen species, and leads to downregulation of the Wnt/-catenin signaling pathway. Taken together, our findings indicate that high levels of intracellular iron, which might be due to low ferroportin expression, play a role in MM pathophysiology. Therefore, DFX may provide a therapeutic option for MM that is driven by deregulated iron homeostasis and/or Pyk2/Wnt signaling.
(徳島大学機関リポジトリ): ● Metadata: 113047
(出版サイトへのリンク): ● Publication site (DOI): 10.18632/oncotarget.11830
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27602957; ● Search Scopus @ Elsevier (PMID): 27602957; ● Search Scopus @ Elsevier (DOI): 10.18632/oncotarget.11830

(徳島大学機関リポジトリ: 113047, DOI: 10.18632/oncotarget.11830, PubMed: 27602957) Takahiro Osuga, Rishu Takimoto, Michihiro Ono, Masahiro Hirakawa, Makoto Yoshida, Yutaka Okagawa, Naoki Uemura, Yohei Arihara, Yasushi Sato, Fumito Tamura, Tsutomu Sato, Satoshi Iyama, Koji Miyanishi, Kohichi Takada, Tsuyoshi Hayashi, Masayoshi Kobune and Junji Kato :
Relationship Between Increased Fucosylation and Metastatic Potential in Colorectal Cancer.,
Journal of the National Cancer Institute, Vol.108, No.9, 2016.

(要約): Thus, fucose-bound liposomes carrying anticancer drugs provide a new strategy for the treatment of CRC patients.
(キーワード): Animals / Antineoplastic Agents, Phytogenic / Camptothecin / Carbocyanines / Cell Line, Tumor / Cell Survival / Colorectal Neoplasms / Drug Carriers / Drug Delivery Systems / 女性 (female) / Fucose / Humans / Immunohistochemistry / リポソーム (liposomes) / Male / Mannose / Mice / Middle Aged / ナノ粒子 (nanoparticles) / Neoplasm Transplantation / Proteins
(出版サイトへのリンク): ● Publication site (DOI): 10.1093/jnci/djw038
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27075853; ● Summary page in Scopus @ Elsevier: 2-s2.0-84992315657

(DOI: 10.1093/jnci/djw038, PubMed: 27075853, Elsevier: Scopus) Kazuyuki Murase, Kohichi Takada, Yusuke Kamihara, Makoto Usami, Masahiro Yoshida, Ayumi Tatekoshi, Akari Hashimoto, Yohei Arihara, Naotaka Hayasaka, Shogo Miura, Satoshi Iyama, Tsutomu Sato, Yasushi Sato, Koji Miyanishi, Masayoshi Kobune, Makoto Emori, Mitsunori Kaya, Toshihiko Yamashita, Shintaro Sugita, Tadashi Hasegawa and Junji Kato :
[Treatment Outcomes of Adult-Onset Ewing Sarcoma: A Single-Center Retrospective Study of Five Cases].,
Japanese Journal of Cancer and Chemotherapy, Vol.43, No.8, 1015-1018, 2016.

(要約): The prognosis of patients with adult-onset ES is poor; however, combined modality therapy, including VDC-IE, was demonstrated to improve the outcome of patients in the present study. Nevertheless, the patient with tumor size exceeding 8 cm, metastasis, and high LDH levels, relapsed 1 year after treatment, as reported previously. Further investigation is required to clarify the factors affecting prognosis in adults, and to develop effective therapies for patients with a poor prognosis.
(キーワード): Adult / Antineoplastic Combined Chemotherapy Protocols / Bone Neoplasms / Female / Humans / Male / Middle Aged / Retrospective Studies / Sarcoma, Ewing / Treatment Outcome / Young Adult
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27539047; ● Search Scopus @ Elsevier (PMID): 27539047

(PubMed: 27539047) Masakazu Hori, Masanori Someya, Yoshihisa Matsumoto, Kensei Nakata, Mio Kitagawa, Tomokazu Hasegawa, Takaaki Tsuchiya, Yuki Fukushima, Toshio Gocho, Yasushi Sato, Hiroyuki Ohnuma, Junji Kato, Shintaro Sugita, Tadashi Hasegawa and Koh-Ichi Sakata :
Influence of XRCC4 expression in esophageal cancer cells on the response to radiotherapy.,
Medical Molecular Morphology, Vol.50, No.1, 25-33, 2016.

(要約): DNA double-strand break (DSB) is one of the most serious forms of damage induced by ionizing irradiation and is mainly repaired by the non-homologous end joining (NHEJ) repair. Immunohistochemical analysis of proteins involved in NHEJ, such as XRCC4 (X-ray repair cross-complementing protein 4), Ku86 and DNA-PKcs (DNA-dependent protein kinase, catalytic subunits), may be useful for predicting tumor radiosensitivity. We examined 92 patients with esophageal squamous cell carcinoma (ECSS) who were treated by radiotherapy between 1999 and 2008. Immunohistochemical examination of tumor tissue for Ki-67 and DSB-related proteins, including XRCC4, Ku86, and DNA-PKcs, was performed using pretreatment biopsy specimens. Low expression of XRCC4 was detected in 31 of 92 examined samples (33.7 %). The 5-year overall survival (OS) rate was 67.7 % in the low expression group and 31.0 % in the high expression group (P = 0.00). Multivariate analysis confirmed that advanced T-stage (HR 3.24, P = 0.01), radiation dose less than 66 Gy (HR 2.23, P = 0.02), absence of systemic chemotherapy (HR 2.59, P = 0.05), and high expression of XRCC4 (HR 12.0, P = 0.02) were independent prognostic factors for predicting poor OS. Other DSB-related proteins and Ki-67 were not predictive factors. XRCC4 expression might have an influence on results of radiotherapy for patients with ESCC.
(キーワード): Aged / Aged, 80 and over / DNA-Activated Protein Kinase / DNA-Binding Proteins / Esophageal Neoplasms / Female / Humans / Ku Autoantigen / Male / Middle Aged / Multivariate Analysis / Neoplasm Recurrence, Local / Neoplasm Staging / Proportional Hazards Models / Treatment Outcome
(出版サイトへのリンク): ● Publication site (DOI): 10.1007/s00795-016-0144-5
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27338590; ● Search Scopus @ Elsevier (PMID): 27338590; ● Search Scopus @ Elsevier (DOI): 10.1007/s00795-016-0144-5

(DOI: 10.1007/s00795-016-0144-5, PubMed: 27338590) Michihiro Ono, Rishu Takimoto, Takahiro Osuga, Yutaka Okagawa, Masahiro Hirakawa, Makoto Yoshida, Yohei Arihara, Naoki Uemura, Naoki Hayasaka, Shogo Miura, Teppei Matsuno, Fumito Tamura, Yasushi Sato, Tsutomu Sato, Satoshi Iyama, Koji Miyanishi, Kohichi Takada, Masayoshi Kobune and Junji Kato :
Targeting Notch-1 positive acute leukemia cells by novel fucose-bound liposomes carrying daunorubicin.,
Oncotarget, Vol.7, No.25, 38586-38597, 2016.

(要約): Complete remission by induction therapy in acute myelogenous leukemia (AML) can be achieved due to improvements in supportive and optimized therapy. However, more than 20% of patients will still need to undergo salvage therapy, and most will have a poor prognosis. Determining the specificity of drugs to leukemia cells is important since this will maximize the dose of chemotherapeutic agents that can be administered to AML patients. In turn, this would be expected to lead to reduced drug toxicity and its increased efficacy. We targeted Notch-1 positive AML cells utilizing fucose-bound liposomes, since activation of Notch-1 is required for O-fucosylation. Herein, we report that intravenously injected, L-fucose-bound liposomes containing daunorubicin can be successfully delivered to AML cells that express fucosylated antigens. This resulted in efficient tumor growth inhibition in tumor-bearing mice and decreased proliferation of AML patient-derived leukemia cells. Thus, biological targeting by fucose-bound liposomes that takes advantage of the intrinsic characteristics of AML cells could be a promising new strategy for Notch-1 positive-AML treatment.
(徳島大学機関リポジトリ): ● Metadata: 113046
(出版サイトへのリンク): ● Publication site (DOI): 10.18632/oncotarget.9558
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27233074; ● Search Scopus @ Elsevier (PMID): 27233074; ● Search Scopus @ Elsevier (DOI): 10.18632/oncotarget.9558

(徳島大学機関リポジトリ: 113046, DOI: 10.18632/oncotarget.9558, PubMed: 27233074) Tomohiro Kubo, Yutaka Kawano, Nobuaki Himuro, Shintaro Sugita, Yasushi Sato, Kazuma Ishikawa, Kohichi Takada, Kazuyuki Murase, Koji Miyanishi, Tsutomu Sato, Rishu Takimoto, Masayoshi Kobune, Takayuki Nobuoka, Koichi Hirata, Tetsuji Takayama, Mitsuru Mori, Tadashi Hasegawa and Junji Kato :
BAK is a predictive and prognostic biomarker for the therapeutic effect of docetaxel treatment in patients with advanced gastric cancer.,
Gastric Cancer, Vol.19, No.3, 827-837, 2016.

(要約): Preoperative chemotherapy is a promising strategy for downstaging advanced gastric cancer before radical resection, although severe adverse events can occur and clinical outcomes are often unsatisfactory. To identify predictive biomarkers of drug sensitivity, we used a well-designed functional apoptosis assay and assessed the correlations between chemosensitivity and clinical outcomes. Drug sensitivity to docetaxel, cisplatin, and 5-fluorouracil was examined in 11 gastric cancer cell lines. BCL2-homology domain 3 (BH3) profiling was performed and assessed for correlations with drug sensitivity. Immunohistochemical staining of clinical gastric cancer specimens was performed before preoperative chemotherapy, and correlations with histopathological responses and clinical outcomes were assessed. BIM (BCL2L11)-BH3 profiling results correlated with docetaxel sensitivity and BAK protein expression, whose knockdown caused docetaxel resistance. The BAK expression indexes of 69 gastric cancer specimens before preoperative chemotherapy (including docetaxel treatment) were determined by multiplying numerical values describing the degrees of BAK positivity and staining intensity observed. Patients whose specimens showed good chemotherapeutic histopathological responses had higher BAK indexes than those with poor responses. Patients with BAK index values 3 showed improved progression-free survival (HR, 2.664; 95 % CI, 1.352-5.248; P = 0.005) and overall survival (HR, 3.390; 95 % CI, 1.549-7.422; P = 0.002). BH3 profiling clearly showed that BIM expression, which depends on BAK expression, correlated with docetaxel sensitivity. BAK expression in gastric cancer is thus predictive of chemotherapeutic responses to docetaxel and clinical prognosis in patients treated with preoperative chemotherapy.
(出版サイトへのリンク): ● Publication site (DOI): 10.1007/s10120-015-0557-1
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26486506; ● Summary page in Scopus @ Elsevier: 2-s2.0-84944937274

(DOI: 10.1007/s10120-015-0557-1, PubMed: 26486506, Elsevier: Scopus) Soushi Ibata, Tsutomu Sato, Kohichi Takada, Ayumi Tatekoshi, Akari Hashimoto, Yusuke Kamihara, Wataru Jomen, Hiroto Horiguchi, Kaoru Ono, Kazuyuki Murase, Satoshi Iyama, Koji Miyanishi, Yasushi Sato, Rishu Takimoto, Masayoshi Kobune and Junji Kato :
Isoform D of vascular endothelial growth factor in systemic capillary leak syndrome: a case report.,
Journal of Medical Case Reports, Vol.10, 2016.

(要約): In our patient, isoform D of vascular endothelial growth factor (instead of vascular endothelial growth factor) may have been a causative factor of hypotensive crises, since isoform D contributes to vascular endothelial growth factor receptor-2 signaling, which is the major mediator of the permeability-enhancing effects of vascular endothelial growth factor. We suggest the measurement of isoform D of vascular endothelial growth factor in patients with systemic capillary leak syndrome in whose serum vascular endothelial growth factor is not elevated.
(キーワード): Adult / Angiogenesis Inhibitors / Biomarkers / Capillary Leak Syndrome / Humans / Hypotension / Male / Protein Isoforms / Thalidomide / Vascular Endothelial Growth Factor D
(徳島大学機関リポジトリ): ● Metadata: 114535
(出版サイトへのリンク): ● Publication site (DOI): 10.1186/s13256-016-0894-7
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27386947; ● Search Scopus @ Elsevier (PMID): 27386947; ● Search Scopus @ Elsevier (DOI): 10.1186/s13256-016-0894-7

(徳島大学機関リポジトリ: 114535, DOI: 10.1186/s13256-016-0894-7, PubMed: 27386947) Hiroyuki Ohnuma, Yasushi Sato, Masahiro Hirakawa, Yutaka Okagawa, Takahiro Osuga, Tsuyoshi Hayashi, Tsutomu Sato, Koji Miyanishi, Masayoshi Kobune, Rishu Takimoto, Tamotsu Sagawa, Masakazu Hori, Masanori Someya, Kensei Nakata, Koh-ichi Sakata, Tetsuji Takayama and Junji Kato :
A Phase 1/2 Study of Definitive Chemoradiation Therapy Using Docetaxel, Nedaplatin, and 5-Fluorouracil (DNF-R) for Esophageal Cancer.,
International Journal of Radiation Oncology*Biology*Physics, Vol.93, No.2, 382-390, 2015.

(要約): Patient survival in esophageal cancer (EC) remains poor. The purpose of this study was to investigate a regimen of definitive chemoradiation therapy (CRT) that exerts good local control of EC. We performed a phase 1/2 study to assess the safety and efficacy of CRT with docetaxel, nedaplatin, and 5-fluorouracil (DNF-R). Eligible patients presented with stage IB to IV EC. Patients received 2 cycles of docetaxel (20, 30, or 40 mg/m(2)) and nedaplatin (50 mg/m(2)) on days 1 and 8 and a continuous infusion of 5-fluorouracil (400 mg/m(2)/day) on days 1 to 5 and 8 to 12, every 5 weeks, with concurrent radiation therapy (59.4 Gy/33 fractions). The recommended dose (RD) was determined using a 3 + 3 design. In the phase 1 study, the dose-limiting toxicities were neutropenia and thrombocytopenia. The RD of docetaxel was determined to be 20 mg/m(2). In the phase 2 study, grade 3 to 4 acute toxicities included neutropenia (42.8%), febrile neutropenia (7.14%), thrombocytopenia (17.9%), and esophagitis (21.4%). Grade 3 to 4 late radiation toxicity included esophagostenosis (10.7%). The complete response rate was 82.1% (95% confidence interval: 67.9-96.3%). Both the median progression-free survival and overall survival were 41.2 months. DNF-R showed good tolerability and strong antitumor activity, suggesting that it is a potentially effective therapeutic regimen for EC.
(キーワード): Aged / Antineoplastic Combined Chemotherapy Protocols / Chemoradiotherapy / Disease-Free Survival / Esophageal Neoplasms / Esophagitis / Feasibility Studies / Female / Fluorouracil / Humans / Male / Maximum Tolerated Dose / Middle Aged / Neutropenia / Organoplatinum Compounds / Pneumonia / Radiotherapy Dosage / Stomatitis / Taxoids
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.ijrobp.2015.05.041
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26232855; ● Summary page in Scopus @ Elsevier: 2-s2.0-84941315731

(DOI: 10.1016/j.ijrobp.2015.05.041, PubMed: 26232855, Elsevier: Scopus) Takahiro Goji, Tetsuo Kimura, Hiroshi Miyamoto, Masanori Takehara, kaizo Kagamoto, Yasuyuki Okada, Jun Okazaki, Yoshifumi Takaoka, Yoshihiko Miyamoto, Yasuhiro Mitsui, Tatsunao Sueuchi, Kumiko Tanaka, Yasuteru Fujino, Sayo Matsumoto, Toshi Takaoka, Shinji Kitamura, Koichi Okamoto, Masako Kimura, Masahiro Sogabe, Naoki Muguruma, Toshiya Okahisa, Yasuhiro Sato, Tamotsu Sagawa, Koji Fujikawa, Yasushi Sato, Hitoshi Ikushima and Tetsuji Takayama :
A Phase I/II Study of Fixed-dose-rate Gemcitabine and S-1 with Concurrent Radiotherapy for Locally Advanced Pancreatic Cancer,
Cancer Chemotherapy and Pharmacology, Vol.76, No.3, 615-620, 2015.

(要約): This study was conducted to identify the maximum-tolerated dose (MTD) of fixed-dose-rate gemcitabine (FDR-gem) administered concurrently with S-1 and radical radiation for locally advanced pancreatic cancer (LAPC) and to provide efficacy and safety data. Patients with unrespectable pancreatic cancer confined to the pancreatic region were treated with FDR-gem (300-400 mg/m(2), 5 mg/m(2)/min) on days 1, 8, 22, and 29 and 60 mg/m(2) of S-1 orally on days 1-14, 22-35. A total radiation dose of 50.4 Gy (1.8 Gy/day, 28 fractions) was delivered concurrently. Twenty-five patients were enrolled; all were evaluable for toxicity assessment. In phase I, eight patients were treated in sequential cohorts of three to five patients per dose level. The MTD was reached at level 2, and dose-limiting toxicities were neutropenia and thrombocytopenia. The recommended doses were 300 mg/m(2) of gemcitabine and 60 mg/m(2) of S-1 daily. The overall response rate was 25% and disease control rate (partial response plus stable disease) was 92%. The progression-free survival was 11.0 months. The median overall survival and 1-year survival rates were 16.0 months and 73%, respectively. The combination of FDR-gem and S-1 with radiation is a feasible regimen that shows favorable antitumor activity with an acceptable safety profile in patients with LAPC.
(徳島大学機関リポジトリ): ● Metadata: 110046
(出版サイトへのリンク): ● Publication site (DOI): 10.1007/s00280-015-2835-3
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26220846; ● Summary page in Scopus @ Elsevier: 2-s2.0-84939568942

(徳島大学機関リポジトリ: 110046, DOI: 10.1007/s00280-015-2835-3, PubMed: 26220846, Elsevier: Scopus) Yutaka Okagawa, 佐藤康史, Hiroyuki Onuma, Takahiro Osuga, Tsuyoshi Hayashi, Tsutomu Sato, Koji Miyanishi, Masayoshi Kobune, Rishu Takimoto, Junji Kato :
[A Case of Fanconi Syndrome Induced by Zoledronic Acid in a Metastatic Colorectal Cancer Patient].,
癌と化学療法, Vol.42, No.7, 867-870, 2015年.

(要約): A 60s-year-old woman with metastatic colorectal cancer was treated using mFOLFOX6 plus bevacizumab. Zoledronic acid was also administered owing to the presence of bone metastasis. The patient was admitted to our hospital with progressive hypokalemia, hypocalcemia, hypophosphatemia, and proximal renal tubular dysfunction. A diagnosis of Fanconi syndrome was made, and was believed to be induced by zoledronic acid treatment. This treatment was discontinued, and the patient's renal tubular function recovered. Denosumab was subsequently administered to treat the bone metastasis, and no renal tubular dysfunction occurred. It was possible to continue chemotherapy, and a complete response was obtained. Fanconi syndrome induced by zoledronic acid is rare, but it may hinder chemotherapy. Therefore, monitoring renal tubular function is recommended during therapy with zoledronic acid.
(キーワード): Antineoplastic Combined Chemotherapy Protocols / Bone Density Conservation Agents / Bone Neoplasms / Colorectal Neoplasms / Diphosphonates / Fanconi Syndrome / Female / Humans / Imidazoles / Positron-Emission Tomography
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26197752; ● Search Scopus @ Elsevier (PMID): 26197752

(PubMed: 26197752) Yasuhiro Mitsui, Yasushi Sato, Hiroshi Miyamoto, Yasuteru Fujino, Toshi Takaoka, Jinsei Miyoshi, Miwako Kagawa, Hiroyuki Ohnuma, Masahiro Hirakawa, Tomohiro Kubo, Takahiro Osuga, Tamotsu Sagawa, Yasuhiro Sato, Yasuo Takahashi, shinichi Katsuki, Toshinori Okuda, Rishu Takimoto, Masayoshi Kobune, Takayuki Nobuoka, Koichi Hirata, Junji Kato and Tetsuji Takayama :
Trastuzumab in combination with docetaxel/cisplatin/S-1 (DCS) for patients with HER2-positive metastatic gastric cancer: feasibility and preliminary efficacy.,
Cancer Chemotherapy and Pharmacology, Vol.76, No.2, 375-382, 2015.

(要約): We previously reported that a triplet combination of docetaxel, cisplatin, and S-1 (DCS) is active against metastatic gastric cancer with a very high response rate of 87.1 % in a phase II study. Recently, the efficacy of trastuzumab (T-mab) for the treatment of HER2-positive gastric cancer has been reported. Therefore, we investigated the feasibility and preliminary efficacy of DCS + T-mab (DCS-T) for unresectable HER2-positive metastatic gastric cancer. Patients received oral S-1 (40 mg/m(2) b.i.d.) on days 1-14, intravenous cisplatin (60 mg/m(2)), docetaxel (50 mg/m(2)), and T-mab (8 mg/kg in the first cycle and 6 mg/kg in the second cycle and thereafter) on day 8 every 3 weeks. The study included 16 patients: median age, 60 (34-76) years; males/females, 11:5; intestinal-type/diffuse-type histology, 11:5; and HER2 3+/2+(FISH+), 13:3. The completion rate until the third cycle was 87.5 % (14/16) (95 %CI 71.3-103.7 %). Adverse events of grade 3/4 severity during the first 3 cycles were: leukopenia/neutropenia, 50.0:75.0 %; febrile neutropenia, 12.5 %; diarrhea, 12.5 %; and stomatitis, 12.5 %. All of these side effects were manageable and well controlled. There were no treatment-related deaths. The overall response rate was 93.8 % (15/16), and the response rate in patients with measurable lesions was 100 % (15/15). The median cycle to response was only 1 (1-3 cycles). Non-curative factors disappeared in 56.3 % (9/16) of patients, and conversion surgery (R0 resection) was performed in all these cases. Pathological response rates in primary and metastatic lesions were 88.9 % (8/9) and 100 % (9/9), respectively. The median PFS and OS were not reached during the median follow-up time of 18.3 months ranged from 11.0 to 34.3 months. DCS-T was feasible in patients with unresectable HER2-positive metastatic gastric cancer. The observed response was very promising and warrants further investigation. UMIN000005603.
(キーワード): Adult / Aged / Antibodies, Monoclonal, Humanized / Cisplatin / Drug Combinations / Feasibility Studies / Female / Humans / Male / Middle Aged / Neoplasm Metastasis / Oxonic Acid / Receptor, Epidermal Growth Factor / Stomach Neoplasms / Taxoids / Tegafur
(徳島大学機関リポジトリ): ● Metadata: 109679
(出版サイトへのリンク): ● Publication site (DOI): 10.1007/s00280-015-2807-7
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26099968; ● Summary page in Scopus @ Elsevier: 2-s2.0-84938207398

(徳島大学機関リポジトリ: 109679, DOI: 10.1007/s00280-015-2807-7, PubMed: 26099968, Elsevier: Scopus) Yuka Matsuda, Kenji Okita, Tomohisa Furuhata, Goro Kutomi, Kentaro Yamashita, Yasushi Sato, Rishu Takimoto and Koichi Hirata :
Evaluation of the validity of chemotherapy-induced nausea and vomiting assessment in outpatients using the Japanese version of the MASCC antiemesis tool.,
Supportive Care in Cancer, Vol.23, No.11, 3331-3339, 2015.

(要約): The results of the study showed that the Japanese version of MAT is a highly reliable tool for CINV assessment, indicating that it is valid for assessing CINV in outpatients.
(キーワード): Adult / Aged / Antiemetics / Antineoplastic Agents / Cross-Over Studies / Female / Hospitals / Humans / Incidence / Japan / Male / Middle Aged / Nausea / Neoplasms / Outpatients / Prospective Studies / Reproducibility of Results / Surveys and Questionnaires / Vomiting
(出版サイトへのリンク): ● Publication site (DOI): 10.1007/s00520-015-2780-z
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26003425; ● Search Scopus @ Elsevier (PMID): 26003425; ● Search Scopus @ Elsevier (DOI): 10.1007/s00520-015-2780-z

(DOI: 10.1007/s00520-015-2780-z, PubMed: 26003425) Toshifumi Hoki, Koji Miyanishi, Shingo Tanaka, Kohichi Takada, Yutaka Kawano, Akira Sakurada, Masanori Sato, Tomohiro Kubo, Tsutomu Sato, Yasushi Sato, Rishu Takimoto, Masayoshi Kobune and Junji Kato :
Increased duodenal iron absorption through up-regulation of divalent metal transporter 1 from enhancement of iron regulatory protein 1 activity in patients with nonalcoholic steatohepatitis.,
Hepatology, Vol.62, No.3, 751-761, 2015.

(要約): Increased hepatic iron accumulation is thought to be involved in the pathogenesis of nonalcoholic steatohepatitis (NASH). Hepatic iron accumulation, as well as oxidative DNA damage, is significantly increased in NASH livers. However, the precise mechanism of iron accumulation in the NASH liver remains unclear. In this study, 40 cases with a diagnosis of NASH (n = 25) or simple steatosis (SS; n = 15) by liver biopsy were enrolled. An oral iron absorption test (OIAT) was used, in which 100 mg of sodium ferrous citrate was administered to each individual. The OIAT showed that absorption of iron from the gastrointestinal (GI) tract was increased significantly in NASH patients, compared to SS and control subjects. Iron reduction therapy was effective in patients with NASH, who exhibited iron deposition in the liver and no alanine aminotransferase improvement after other therapies (n = 9). Serum hepcidin concentration and messenger RNA (mRNA) levels of divalent metal transporter 1 (DMT1) also were significantly elevated in patients with NASH. OIAT results were correlated with grade of liver iron accumulation and DMT1 mRNA levels. Then, we demonstrated that DMT1 mRNA levels increased significantly in Caco-2/TC7 cell monolayers cultured in transwells with serum from NASH patients. An electrophoresis mobility shift assay showed activation of iron regulatory protein (IRP) in those cells, and IRP1 small interfering RNA clearly inhibited the increase of DMT1 mRNA levels.
(キーワード): Adult / Analysis of Variance / Biopsy, Needle / Caco-2 Cells / Case-Control Studies / Cells, Cultured / Duodenum / Female / Gene Expression Regulation / Humans / Immunohistochemistry / Iron / Iron Regulatory Protein 1 / Male / Middle Aged / Non-alcoholic Fatty Liver Disease / RNA, Messenger / Real-Time Polymerase Chain Reaction / Reference Values / Retrospective Studies / Statistics, Nonparametric / Transcriptional Activation / Up-Regulation
(出版サイトへのリンク): ● Publication site (DOI): 10.1002/hep.27774
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25753988; ● Search Scopus @ Elsevier (PMID): 25753988; ● Search Scopus @ Elsevier (DOI): 10.1002/hep.27774

(DOI: 10.1002/hep.27774, PubMed: 25753988) Yasuo Hirayama, Kunihiko Ishitani, Yasushi Sato, Satoshi Iyama, Kohichi Takada, Kazuyuki Murase, Hiroyuki Kuroda, Yasuhiro Nagamachi, Yuichi Konuma, Akihito Fujimi, Tamotsu Sagawa, Kaoru Ono, Hiroto Horiguchi, Takeshi Terui, Kazuhiko Koike, Toshiro Kusakabe, Tsutomu Sato, Rishu Takimoto, Masayoshi Kobune and Junji Kato :
Effect of duloxetine in Japanese patients with chemotherapy-induced peripheral neuropathy: a pilot randomized trial.,
International Journal of Clinical Oncology, Vol.20, No.5, 866-871, 2015.

(要約): Our data suggests that duloxetine has a beneficial effect on CIPN caused by oxaliplatin, paclitaxel, vincristine, or bortezomib in Japanese patients.
(キーワード): Aged / Antineoplastic Agents / Cross-Over Studies / Duloxetine Hydrochloride / Female / Humans / Male / Middle Aged / Peripheral Nervous System Diseases / Pilot Projects / Serotonin and Noradrenaline Reuptake Inhibitors / Vitamin B 12
(出版サイトへのリンク): ● Publication site (DOI): 10.1007/s10147-015-0810-y
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25762165; ● Search Scopus @ Elsevier (PMID): 25762165; ● Search Scopus @ Elsevier (DOI): 10.1007/s10147-015-0810-y

(DOI: 10.1007/s10147-015-0810-y, PubMed: 25762165) Hirotoshi Ishiwatari, Tsuyoshi Hayashi, Makoto Yoshida, Michihiro Ono, Tsutomu Sato, Koji Miyanishi, Yasushi Sato, Rishu Takimoto, Masayoshi Kobune and Junji Kato :
Phase I trial of oral S-1 combined with hepatic arterial infusion of gemcitabine in unresectable biliary tract cancer.,
Cancer Chemotherapy and Pharmacology, Vol.75, No.4, 805-812, 2015.

(要約): The MTD of oral S-1 in GS therapy is 80 mg/m(2). Furthermore, HAI of gemcitabine may reduce the rate of grade 3 and 4 neutropenia in BTC patients receiving GS therapy.
(キーワード): Administration, Oral / Adult / Aged / Antineoplastic Combined Chemotherapy Protocols / Biliary Tract Neoplasms / Deoxycytidine / Dose-Response Relationship, Drug / Drug Administration Schedule / Drug Combinations / Female / Hepatic Artery / Humans / Infusions, Intra-Arterial / Male / Maximum Tolerated Dose / Middle Aged / Neutropenia / Oxonic Acid / Tegafur
(出版サイトへのリンク): ● Publication site (DOI): 10.1007/s00280-015-2704-0
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25687990; ● Search Scopus @ Elsevier (PMID): 25687990; ● Search Scopus @ Elsevier (DOI): 10.1007/s00280-015-2704-0

(DOI: 10.1007/s00280-015-2704-0, PubMed: 25687990) Hirotoshi Ishiwatari, Tsuyoshi Hayashi, Makoto Yoshida, Michihiro Ono, Tsutomu Sato, Koji Miyanishi, Yasushi Sato, Rishu Takimoto, Masayoshi Kobune, Hiroyuki Masuko, Atsushi Miyamoto, Tomoko Sonoda and Junji Kato :
EUS-guided celiac plexus neurolysis by using highly viscous phenol-glycerol as a neurolytic agent (with video).,
Gastrointestinal Endoscopy, Vol.81, No.2, 479-483, 2015.

(キーワード): Abdominal Neoplasms / Abdominal Pain / Aged / Celiac Plexus / Endosonography / Ethanol / Feasibility Studies / Female / Glycerol / Humans / Male / Middle Aged / Nerve Block / Pain Measurement / Phenol / Pilot Projects / Prospective Studies / Treatment Outcome / Ultrasonography, Interventional
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.gie.2014.10.031
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25616759; ● Search Scopus @ Elsevier (PMID): 25616759; ● Search Scopus @ Elsevier (DOI): 10.1016/j.gie.2014.10.031

(DOI: 10.1016/j.gie.2014.10.031, PubMed: 25616759) Yasushi Sato, Hiroyuki Ohnuma, Masahiro Hirakawa, Minoru Takahashi, Takahiro Osuga, Yutaka Okagawa, Kazuyuki Murase, Kohichi Takada, Yutaka Kawano, Satoshi Iyama, Tsuyoshi Hayashi, Tsutomu Sato, Koji Miyanishi, Rishu Takimoto, Masayoshi Kobune, Kenji Okita, Toru Mizuguchi, Tomohisa Furuhata, Koichi Hirata and Junji Kato :
A dose-escalation study of oxaliplatin/capecitabine/irinotecan (XELOXIRI) and bevacizumab as a first-line therapy for patients with metastatic colorectal cancer.,
Cancer Chemotherapy and Pharmacology, Vol.75, No.3, 587-594, 2015.

(要約): XELOXIRI/bevacizumab is a feasible regimen for patients with mCRC, neutropenia was the DLT, and the RD of irinotecan is 150 mg/m(2). The response rate observed is very promising and warrants further investigation.
(キーワード): Aged / Antibodies, Monoclonal, Humanized / Antineoplastic Combined Chemotherapy Protocols / Bevacizumab / Camptothecin / Capecitabine / Colorectal Neoplasms / Deoxycytidine / Disease-Free Survival / Dose-Response Relationship, Drug / Feasibility Studies / Fluorouracil / Humans / Male / Maximum Tolerated Dose / Middle Aged / Neoplasm Metastasis / Organoplatinum Compounds / Treatment Outcome
(出版サイトへのリンク): ● Publication site (DOI): 10.1007/s00280-014-2672-9
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25577134; ● Search Scopus @ Elsevier (PMID): 25577134; ● Search Scopus @ Elsevier (DOI): 10.1007/s00280-014-2672-9

(DOI: 10.1007/s00280-014-2672-9, PubMed: 25577134) 保木寿文, 宮西浩嗣, 河野豊, 山田尚太, 原田耕平, 平川昌宏, 田村文人, 石川和真, 高田弘一, 佐藤勉, 佐藤康史, 瀧本理修, 小船雅義, 長谷川匡, 加藤淳二 :
Recombinant interleukin-2を投与し6年間経過観察している肺転移を伴う肝類上皮血管内皮腫の1例,
肝臓, Vol.56, No.7, 356-365, 2015年.

(要約): 症例は37歳女性．2009年1月，健診で肝機能障害を指摘され近医を受診し，単純CTにて肝および肺に多発結節病変を認められたため精査加療目的に当科紹介となった．造影CTでは肝被膜下を中心に境界明瞭な低吸収域が多発し癒合している所見を肝両葉に認めた．肝生検で豊富な硝子様の線維性間質内に腫瘍細胞を認め，免疫染色にて第VIII因子関連抗原，CD34陽性であり肝原発の類上皮血管内皮腫(hepatic epithelioid hemangioendothelioma:HEHE)と診断した．同年4月よりrecombinant interleukin-2(rIL-2)の投与を開始し，6年間外来通院にて治療を継続し，病変体積の減少が得られている．HEHEの生物学的悪性度は低いとされるが，既に腫瘍が肝全体を占めるように多発した切除不能例として発見されることが多い．本疾患の長期間の臨床経過を示した報告が少ないことから，本症例について報告する．
(出版サイトへのリンク): ● Publication site (DOI): 10.2957/kanzo.56.356
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1390282679770428928; ● Search Scopus @ Elsevier (DOI): 10.2957/kanzo.56.356

(DOI: 10.2957/kanzo.56.356, CiNii: 1390282679770428928) 神原悠輔, 佐藤康史, 高田弘一, 岡川泰, 井山諭, 佐藤勉, 宮西浩嗣, 瀧本理修, 小船雅義, 加藤淳二 :
食道癌および中咽頭癌に対する根治的化学放射線併用療法の晩期有害事象と考えられたtherapy-related myelodysplastic syndromeの1例,
日本消化器病学会雑誌, Vol.112, No.9, 1664-1673, 2015年.

(要約): 症例は80歳男性．中咽頭癌および胸部上部食道癌の重複癌にて根治的化学放射線療法を2コース施行し，CRを得た．6年後徐々に進行する貧血を認め，骨髄検査と経過よりtherapy-related myelodysplastic syndrome(t-MDS)と診断した．晩期有害事象としてまれだが，t-MDSは極めて予後不良であり，治療前の十分な説明と終了後の慎重な経過観察が必要である．
(出版サイトへのリンク): ● Publication site (DOI): 10.11405/nisshoshi.112.1664
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1390001206401943168; ● Search Scopus @ Elsevier (DOI): 10.11405/nisshoshi.112.1664

(DOI: 10.11405/nisshoshi.112.1664, CiNii: 1390001206401943168) 大須賀崇裕, 佐藤康史, 石川和真, 大沼啓之, 岡川泰, 杉田真太朗, 秋山剛英, 小船雅義, 瀧本理修, 加藤淳二 :
拡大内視鏡観察が術前診断に有用であった十二指腸Brunner腺過誤腫の1例,
日本消化器内視鏡学会雑誌, Vol.57, No.10, 2441-2447, 2015年.

(要約): 症例は70歳男性．十二指腸球部にポリープを認め，精査加療目的に当科紹介．上部消化管内視鏡検査では，十二指腸球部に基部を持ち，頭部は発赤調で茎部は頭部と同等の太さの，茸状の外観を呈した山田IV型病変を認めた．拡大観察では，頭部に胃上皮化生または異所性胃粘膜と考えられる所見と微小な開口部を認めた．診断的治療目的にpolypectomyを施行したところ，組織学的には表層粘膜に胃上皮化生を伴う成熟脂肪組織の豊富な十二指腸Brunner腺過誤腫であった．Brunner腺過誤腫は，過形成性のBrunner腺に脂肪組織など他の要素が混在するもので，しばしば胃上皮化生を伴う<sup>1)</sup>とされる．本例では，拡大内視鏡観察によりBrunner腺由来病変に特徴的な所見の指摘が可能であった．
(出版サイトへのリンク): ● Publication site (DOI): 10.11280/gee.57.2441
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1390282679199443584; ● Summary page in Scopus @ Elsevier: 2-s2.0-84947228806

(DOI: 10.11280/gee.57.2441, CiNii: 1390282679199443584, Elsevier: Scopus) 田村文人, 河野豊, 宮西浩嗣, 久保智洋, 神原悠輔, 岡川泰, 石川和真, 高田弘一, 林毅, 佐藤勉, 佐藤康史, 小船雅義, 瀧本理修, 川本雅樹, 目黒誠, 水口徹, 荻野次郎, 長谷川匡, 米田憲秀, 佐々木素子, 加藤淳二 :
肝生検で高分化型肝細胞癌との鑑別が困難であった多発肝細胞腺腫の1切除例,
肝臓, Vol.56, No.11, 584-595, 2015年.

(要約): 症例は40歳代女性．検診の腹部超音波検査で肝血管腫が疑われ当科を紹介受診．造影CT検査で肝血管腫以外に多発肝腫瘍を認め，精査目的に入院となった．Gd-EOB-MRI検査では，S2, S5に腫瘤像が認められ，T1WIで低信号，動脈相で等信号，門脈相，平衡相及び肝細胞相で低信号であった．画像検査では確定診断に至らず，腫瘍生検を施行した．細胞密度の高い異型の乏しい腫瘍細胞で，肝細胞腺腫や高分化型肝細胞癌が疑われ，肝部分切除術と術中RFAを施行した．摘出標本の免疫染色にてliver fatty acid binding protein(L-FABP)の発現低下を認め，Hepatocyte nuclear factor 1α-inactivated type(HNF1α-inactivated type)の多発肝細胞腺腫と診断した．多発肝細胞腺腫は稀であり文献的考察を加え報告する．
(出版サイトへのリンク): ● Publication site (DOI): 10.2957/kanzo.56.584
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1390001204794558976; ● Search Scopus @ Elsevier (DOI): 10.2957/kanzo.56.584

(DOI: 10.2957/kanzo.56.584, CiNii: 1390001204794558976) Fumito Tamura, Yasushi Sato, Masahiro Hirakawa, Makoto Yoshida, Michihiro Ono, Takahiro Osuga, Yutaka Okagawa, Naoki Uemura, Yohei Arihara, Kazuyuki Murase, Yutaka Kawano, Satoshi Iyama, Kohichi Takada, Tsuyoshi Hayashi, Tsutomu Sato, Koji Miyanishi, Masayoshi Kobune, Rishu Takimoto and Junji Kato :
RNAi-mediated gene silencing of ST6GalNAc I suppresses the metastatic potential in gastric cancer cells.,
Gastric Cancer, Vol.19, No.1, 85-97, 2014.

(要約): ST6GalNAc I may regulate the gene expression of IGF-1 through STAT5b activation in gastric cancer cells and may be a potential target for treatment of metastasizing gastric cancer.
(キーワード): Animals / Antigens, Tumor-Associated, Carbohydrate / Cell Line, Tumor / Cell Movement / Female / Gene Expression Regulation, Enzymologic / Gene Silencing / Humans / Insulin-Like Growth Factor I / Mice, Inbred BALB C / Peritoneal Neoplasms / RNA Interference / STAT5 Transcription Factor / Sialyltransferases / Stomach Neoplasms / Xenograft Model Antitumor Assays
(出版サイトへのリンク): ● Publication site (DOI): 10.1007/s10120-014-0454-z
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25532910; ● Search Scopus @ Elsevier (PMID): 25532910; ● Search Scopus @ Elsevier (DOI): 10.1007/s10120-014-0454-z

(DOI: 10.1007/s10120-014-0454-z, PubMed: 25532910) Satoshi Iyama, Tsutomu Sato, Hiroomi Tatsumi, Akari Hashimoto, Ayumi Tatekoshi, Yusuke Kamihara, Hiroto Horiguchi, Soushi Ibata, Kaoru Ono, Kazuyuki Murase, Kohichi Takada, Yasushi Sato, Tsuyoshi Hayashi, Koji Miyanishi, Emi Akizuki, Takayuki Nobuoka, Toru Mizugichi, Rishu Takimoto, Masayoshi Kobune, Koichi Hirata and Junji Kato :
Efficacy of Enteral Supplementation Enriched with Glutamine, Fiber, and Oligosaccharide on Mucosal Injury following Hematopoietic Stem Cell Transplantation.,
Case Reports in Oncology, Vol.7, No.3, 692-699, 2014.

(要約): The combination of glutamine, fiber and oligosaccharides (GFO) is thought to be beneficial for alleviating gastrointestinal mucosal damage caused by chemotherapy. A commercial enteral supplementation product (GFO) enriched with these 3 components is available in Japan. We performed a retrospective study to test whether oral GFO decreased the severity of mucosal injury following hematopoietic stem cell transplantation (HSCT). Of 44 HSCT patients, 22 received GFO and 22 did not. Severity of diarrhea/mucositis, overall survival, weight loss, febrile illness/documented infection, intravenous hyperalimentation days/hospital days, engraftment, acute and chronic GVHD, and cumulative incidence of relapse were studied. Sex, age, performance status, diagnosis, disease status, and treatment variables were similar in both groups. There were fewer days of diarrhea grade 3-4 in patients receiving GFO than in those who did not (0.86 vs. 3.27 days); the same was true for days of mucositis grade 3-4 (3.86 vs. 6.00 days). Survival at day 100 was 100% in the GFO group, but only 77.3% for the patients not receiving GFO (p = 0.0091, log-rank test). Weight loss and the number of days of intravenous hyperalimentation were better in the GFO group (p < 0.001 and p = 0.0014, respectively). Although not significant, less gut bacterial translocation with Enterococcus species developed in the GFO group (p = 0.0728) than in the non-GFO group. Other outcomes were not affected. To the best of our knowledge, this is the first comparative clinical study of GFO supplementation to alleviate mucosal injury after allo-HSCT. We conclude that glutamine, fiber and oligosaccharide supplementation is an effective supportive therapy to decrease the severity of mucosal damage in HSCT.
(出版サイトへのリンク): ● Publication site (DOI): 10.1159/000368714
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25493082; ● Search Scopus @ Elsevier (PMID): 25493082; ● Search Scopus @ Elsevier (DOI): 10.1159/000368714

(DOI: 10.1159/000368714, PubMed: 25493082) Hiroto Horiguchi, Kohichi Takada, Yusuke Kamihara, Soushi Ibata, Satoshi Iyama, Tsutomu Sato, Tsuyoshi Hayashi, Koji Miyanishi, Yasushi Sato, Rishu Takimoto, Masayoshi Kobune, Ko Kobayashi, Yasuo Hirayama, Naoya Masumori, Tadashi Hasegawa and Junji Kato :
Radiation-induced leiomyosarcoma of the prostate after brachytherapy for prostatic adenocarcinoma.,
Case Reports in Oncology, Vol.7, No.2, 565-570, 2014.

(要約): Radiation therapy (RTx) has been employed as a curative therapy for prostatic adenocarcinoma. RTx-induced sarcomas (RISs) are rare, late adverse events, representing less than 0.2% of all irradiated patients. RISs are more aggressive tumors than prostatic adenocarcinomas. Herein, we present a case with RTx-induced prostatic leiomyosarcoma after permanent brachytherapy for prostatic adenocarcinoma. A 69-year-old male presented with dysuria and gross hematuria. Six years previously, he had been diagnosed with localized prostate cancer and was treated by permanent brachytherapy. Urethroscopy showed stenosis by a tumor at the prostate. Transurethral prostatectomy was performed for a diagnosis. Based on pathological findings, the diagnosis was leiomyosarcoma of the prostate. He was treated with three cycles of neoadjuvant chemotherapy (CTx) that consisted of doxorubicin and ifosfamide (AI), followed by a prostatocystectomy with intrapelvic lymphadenectomy. The tumor extended from the prostate and infiltrated the bladder wall and serosa with lymphatic and venous invasion. The surgical margin was negative, and no residual prostatic adenocarcinoma was observed. The proportion of necrotic tumor cells by neoadjuvant CTx was around 50%. Subsequently, adjuvant CTx was offered, but the patient chose a follow-up without CTx. Local recurrence and lung metastasis were detected by computed tomography 3 months after the surgery. He was treated again with AI. However, CTx was not effective and he died 6 months after the operation. In conclusion, an effective treatment strategy for prostatic sarcoma should be developed in the near future, although the clinical feature of prostatic sarcoma remains unclear due to its rare incidence.
(出版サイトへのリンク): ● Publication site (DOI): 10.1159/000366294
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25232328; ● Search Scopus @ Elsevier (PMID): 25232328; ● Search Scopus @ Elsevier (DOI): 10.1159/000366294

(DOI: 10.1159/000366294, PubMed: 25232328) Yutaka Okagawa, Kohichi Takada, Hiroyuki Hisai, Yutaka Koshiba, Hironori Wada, Etsu Miyazaki, Yusuke Kanari, Yutaka Kawano, Satoshi Iyama, Tsuyoshi Hayashi, Tsutomu Sato, Yasushi Sato, Koji Miyanishi, Masayoshi Kobune, Rishu Takimoto and Junji Kato :
Successful treatment with entecavir for reactivation of hepatitis B virus following systemic chemotherapy in a hepatitis B surface antigen-negative patient with colorectal cancer.,
Internal Medicine, Vol.53, No.16, 1759-1762, 2014.

(要約): Reactivation of hepatitis B virus (HBV) has recently been reported as a fatal complication in patients undergoing cytotoxic chemotherapy. We herein describe a case of reactivation in a 76-year-old man who had undergone pelvic exenteration for colorectal cancer (CRC). He was treated with a modified FOLFOX6 chemotherapy regimen after the operation. Thirteen months later, his laboratory data showed severe liver dysfunction. His hepatitis B surface antigen (HBsAg) test was positive, and his HBV-DNA level was elevated. We diagnosed the patient with HBV reactivation as his HBsAg test was negative before starting chemotherapy. His liver dysfunction improved after administration of entecavir. This is the first report describing HBV reactivation following chemotherapy for an HBsAg-negative CRC patient.
(キーワード): Aged / Antineoplastic Combined Chemotherapy Protocols / Antiviral Agents / Colorectal Neoplasms / Fluorouracil / Guanine / Hepatitis B / Hepatitis B Surface Antigens / Humans / Leucovorin / Male / Organoplatinum Compounds / Treatment Outcome / Virus Activation
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25130106; ● Search Scopus @ Elsevier (PMID): 25130106

(PubMed: 25130106) Hirotoshi Ishiwatari, Tsuyoshi Hayashi, Makoto Yoshida, Michihiro Ono, Hiroyuki Masuko, Tsutomu Sato, Koji Miyanishi, Yasushi Sato, Rishu Takimoto, Masayoshi Kobune, Atsushi Miyamoto, Tomoko Sonoda and Junji Kato :
Phenol-based endoscopic ultrasound-guided celiac plexus neurolysis for East Asian alcohol-intolerant upper gastrointestinal cancer patients: a pilot study.,
World Journal of Gastroenterology : WJG, Vol.20, No.30, 10512-10517, 2014.

(要約): Phenol had similar pain-relieving effects to ethanol in EUS-CPN. Comparing the incidences of inebriation and burning pain, phenol may be superior to ethanol in EUS-CPN procedures.
(キーワード): Abdominal Pain / Aged / Aged, 80 and over / Asian Continental Ancestry Group / Celiac Plexus / Endosonography / Ethanol / Female / Gastrointestinal Neoplasms / Humans / Japan / Male / Middle Aged / Nerve Block / Pain Management / Pain Measurement / Phenol / Pilot Projects / Retrospective Studies / Time Factors / Treatment Outcome
(出版サイトへのリンク): ● Publication site (DOI): 10.3748/wjg.v20.i30.10512
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25132769; ● Search Scopus @ Elsevier (PMID): 25132769; ● Search Scopus @ Elsevier (DOI): 10.3748/wjg.v20.i30.10512

(DOI: 10.3748/wjg.v20.i30.10512, PubMed: 25132769) Akari Hashimoto, Kohichi Takada, Rishu Takimoto, Hiroto Horiguchi, Tsutomu Sato, Satoshi Iyama, Kazuyuki Murase, Kaoru Ono, Ayumi Tatekoshi, Tsuyoshi Hayashi, Koji Miyanishi, 佐藤康史, Masayoshi Kobune, Yasuo Hirayama, Hiroshi Kitamura, Katsuya Nakanishi, Naoya Masumori, Tadashi Hasegawa, Junji Kato :
[Effective treatment of metastatic rhabdomyosarcoma with pazopanib].,
癌と化学療法, Vol.41, No.8, 1041-1044, 2014年.

(要約): Pazopanib, an oral tyrosine kinase inhibitor, is the first molecular-targeted agent approved for the treatment of advanced soft tissue sarcoma(STS). Rhabdomyosarcoma in adults is rare, accounting for less than 3%of all adult STS cases. A 57-year old woman presented with cervical lymphadenopathy. Computed tomography revealed a heterogeneous mass in the retroperitoneum, replacing the entire right kidney. On the basis of the above findings, the patient was diagnosed with alveolar rhabdomyosarcoma. She was first treated with 4 courses of vincristine, actinomycin D, and cyclophosphamide(VAC), which resulted in a partial response. Dose reduction and delay occurred owing to hematological toxicity and febrile neutropenia. As second-line chemotherapy, the patient was administered a single daily dose of 800 mg of pazopanib. Because of an episode of hand-foot syndrome and hepatic impairment, the 800-mg daily dose of pazopanib was reduced to a daily dose of 600 mg, which had to be further reduced to a daily dose of 400 mg owing to fatigue and anorexia. The patient maintained a partial response for a total of 4.3 months when treated with pazopanib. Therefore, this drug may be a new treatment option for patients showing metastatic STS after previous chemotherapy.
(キーワード): Angiogenesis Inhibitors / Biopsy, Needle / Fatal Outcome / Female / Humans / Kidney Neoplasms / Middle Aged / Peritoneal Neoplasms / Pyrimidines / Rhabdomyosarcoma / Sulfonamides
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25132042; ● Search Scopus @ Elsevier (PMID): 25132042

(PubMed: 25132042) Kubo Naoko Birukawa, Kazuyuki Murase, Yasushi Sato, Akemi Kosaka, Akihiro Yoneda, Hiroki Nishita, Ryosuke Fujita, Miyuki Nishimura, Takafumi Ninomiya, Keiko Kajiwara, Miyono Miyazaki, Yusuke Nakashima, Sigenori Ota, Yuya Murakami, Yasunobu Tanaka, Kenjiro Minomi, Yasuaki Tamura and Yoshiro Niitsu :
Activated hepatic stellate cells are dependent on self-collagen, cleaved by membrane type 1 matrix metalloproteinase for their growth.,
The Journal of Biological Chemistry, Vol.289, No.29, 20209-20221, 2014.

(要約): Stellate cells are distributed throughout organs, where, upon chronic damage, they become activated and proliferate to secrete collagen, which results in organ fibrosis. An intriguing property of hepatic stellate cells (HSCs) is that they undergo apoptosis when collagen is resolved by stopping tissue damage or by treatment, even though the mechanisms are unknown. Here we disclose the fact that HSCs, normal diploid cells, acquired dependence on collagen for their growth during the transition from quiescent to active states. The intramolecular RGD motifs of collagen were exposed by cleavage with their own membrane type 1 matrix metalloproteinase (MT1-MMP). The following evidence supports this conclusion. When rat activated HSCs (aHSCs) were transduced with siRNA against the collagen-specific chaperone gp46 to inhibit collagen secretion, the cells underwent autophagy followed by apoptosis. Concomitantly, the growth of aHSCs was suppressed, whereas that of quiescent HSCs was not. These in vitro results are compatible with the in vivo observation that apoptosis of aHSCs was induced in cirrhotic livers of rats treated with siRNAgp46. siRNA against MT1-MMP and addition of tissue inhibitor of metalloproteinase 2 (TIMP-2), which mainly inhibits MT1-MMP, also significantly suppressed the growth of aHSCs in vitro. The RGD inhibitors echistatin and GRGDS peptide and siRNA against the RGD receptor V1 resulted in the inhibition of aHSCs growth. Transduction of siRNAs against gp46, V1, and MT1-MMP to aHSCs inhibited the survival signal of PI3K/AKT/IB. These results could provide novel antifibrosis strategies.
(キーワード): Animals / Apoptosis / 細胞増殖·分化 (cell proliferation and differentiation) / Cell Survival / コラーゲン (collagen) / HSP47 Heat-Shock Proteins / Hepatic Stellate Cells / Humans / I-kappa B Proteins / Integrins / Liver Cirrhosis / Matrix Metalloproteinase 14 / Matrix Metalloproteinase Inhibitors / ノックアウトマウス (knockout mice) / Oligopeptides / Phosphatidylinositol 3-Kinases / Proto-Oncogene Proteins c-akt / RNA, Small Interfering / Rats / Rats, Sprague-Dawley / シグナル伝達 (signal transduction) / Tissue Inhibitor of Metalloproteinase-1
(出版サイトへのリンク): ● Publication site (DOI): 10.1074/jbc.M113.544494
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24867951; ● Search Scopus @ Elsevier (PMID): 24867951; ● Search Scopus @ Elsevier (DOI): 10.1074/jbc.M113.544494

(DOI: 10.1074/jbc.M113.544494, PubMed: 24867951) Akari Hashimoto, Kohichi Takada, Hiroto Horiguchi, Tsutomu Sato, Satoshi Iyama, Kazuyuki Murase, Yusuke Kamihara, Kaoru Ono, Ayumi Tatekoshi, Tsuyoshi Hayashi, Koji Miyanishi, Yasushi Sato, Tomohisa Furuhata, Masayoshi Kobune, Rishu Takimoto, Koichi Hirata and Junji Kato :
Combination Chemotherapy of Azacitidine and Cetuximab for Therapy-Related Acute Myeloid Leukemia following Oxaliplatin for Metastatic Colorectal Cancer.,
Case Reports in Oncology, Vol.7, No.2, 316-322, 2014.

(要約): Therapy-related leukemia (TRL) has been reported to occur after treatment with alkylating agents and/or topoisomerase II inhibitors. Oxaliplatin (OXP) is used as a key drug for the treatment of colorectal cancer (CRC). Cisplatin and carboplatin have been linked with TRL, but the involvement of OXP is questionable. A 74-year-old male was diagnosed with peritoneal metastasis from CRC in July 2011. The patient received nine cycles of 5-fluorouracil (5-FU), leucovorin (LV), and OXP (mFOLFOX-6 regimen) and three cycles of 5-FU and LV only, resulting in a clinical complete response. However, recurrence of CRC was detected by CT within 3 months after the last course of chemotherapy. In April 2013, laboratory tests showed pancytopenia and 15% blast cells. A bone marrow examination revealed multilineage dysplasia and 20.4% myeloblasts. Cytogenetic analysis indicated a complex karyotype that included chromosome 5 and 7 abnormalities. The patient was diagnosed with TRL and treated with a combination of azacitidine (AZA) and cetuximab (Cmab) for both cancers. AZA might be useful in TRL when a patient needs to be treated simultaneously for more than one primary cancer because of its low toxicity. Moreover, Cmab is an effective therapeutic tool in TRL patients with metastatic CRC with the wild-type K-ras gene.
(出版サイトへのリンク): ● Publication site (DOI): 10.1159/000363100
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24932174; ● Search Scopus @ Elsevier (PMID): 24932174; ● Search Scopus @ Elsevier (DOI): 10.1159/000363100

(DOI: 10.1159/000363100, PubMed: 24932174) Yasushi Sato, Tamotsu Sagawa, Masahiro Hirakawa, Hiroyuki Ohnuma, Takahiro Osuga, Yutaka Okagawa, Fumito Tamura, Hiroto Horiguchi, Kohichi Takada, Tsuyoshi Hayashi, Tsutomu Sato, Koji Miyanishi, Rishu Takimoto, Masayoshi Kobune and Junji Kato :
Clinical utility of capsule endoscopy with flexible spectral imaging color enhancement for diagnosis of small bowel lesions.,
Endoscopy International Open, Vol.2, No.2, E80-7, 2014.

(要約): In the assessment of visibility in the 152 vascular lesion images, the ∆E and VAS of FICE set 1, 2, and BM images were significantly higher than that of WL images. In 88 erosion/ulceration images, the ∆E and VAS of FICE set 1 and 2 images were significantly higher than that of WL images. In 21 tumor images, there were no significant differences in ∆E among these modalities. When analyzed on a per-patient basis, FICE settings 1 and 2 had the highest sensitivity (100 %) and specificity (97.3 - 100 %) for vascular lesions. As for erosive/ulcerative lesions, FICE setting 2 had the highest sensitivity (100 %) and specificity (97.2 %). For tumors or polyps, WL had the highest sensitivity (90.9 %) and specificity (87.1 %). In per-lesion analysis, FICE settings 1 and 2 showed significantly superior detection ability over WL for vascular lesions. In the detection of erosive/ulcerative lesions, FICE setting 2 was significantly superior to WL. In tumor images, there was no significant improvement with any of the settings relative to WL images.
(出版サイトへのリンク): ● Publication site (DOI): 10.1055/s-0034-1365526
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26135265; ● Search Scopus @ Elsevier (PMID): 26135265; ● Search Scopus @ Elsevier (DOI): 10.1055/s-0034-1365526

(DOI: 10.1055/s-0034-1365526, PubMed: 26135265) Satoshi Iyama, Kazuyuki Murase, Tsutomu Sato, Akari Hashimoto, Ayumi Tatekoshi, Hiroto Horiguchi, Yusuke Kamihara, Kaoru Ono, Shohei Kikuchi, Kohichi Takada, Yutaka Kawano, Tsuyoshi Hayashi, Koji Miyanishi, Yasushi Sato, Rishu Takimoto, Masayoshi Kobune, Satoru Mori, Junji Kato, Toshiharu Yamashita and Junji Kato :
Narrowband ultraviolet B phototherapy ameliorates acute graft-versus-host disease by a mechanism involving in vivo expansion of CD4+CD25+Foxp3+ regulatory T cells.,
International Journal of Hematology, Vol.99, No.4, 471-476, 2014.

(要約): Narrowband ultraviolet B phototherapy (NB-UVB) is a therapeutic alternative for haematopoietic stem cell transplantation-related skin graft-versus-host disease (GVHD). The beneficial effects of this intervention may be induced by direct irradiation of inflammatory cells in the skin; however, the putative involvement of indirect effects on systemic immunity has not been elucidated. To address this issue, 11 acute skin GVHD patients refractory to standard corticosteroid treatment and with no gut/liver involvement were treated with NB-UVB irradiation. The median number of treatments was 10 times, with a mean cumulative exposure of 6.36 J/cm(2). No other immunosuppressive therapy was initiated during irradiation. Eight patients achieved an objective complete response, two had a partial response, and one showed no change. None of the patients experienced progressive skin GVHD or newly diagnosed gut/liver GVHD. NB-UVB was well tolerated, with no patients discontinuing irradiation due to toxicity. We additionally demonstrated by flow cytometry that NB-UVB irradiation induces the increment of the proportion of regulatory T cell (Tregs) in patients' peripheral blood. These results suggest that NB-UVB may exert beneficial effects on steroid-refractory skin GVHD through the expansion of Tregs.
(キーワード): Adult / Aged / Female / Forkhead Transcription Factors / Graft vs Host Disease / Hematopoietic Stem Cell Transplantation / Humans / Immunophenotyping / Interleukin-2 Receptor alpha Subunit / Male / Middle Aged / Phenotype / Skin Diseases / T-Lymphocytes, Regulatory / Transplantation, Homologous / Treatment Outcome / Ultraviolet Therapy / Young Adult
(出版サイトへのリンク): ● Publication site (DOI): 10.1007/s12185-014-1530-1
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24557710; ● Search Scopus @ Elsevier (PMID): 24557710; ● Search Scopus @ Elsevier (DOI): 10.1007/s12185-014-1530-1

(DOI: 10.1007/s12185-014-1530-1, PubMed: 24557710) K Ono, T Sato, S Iyama, A Tatekoshi, A Hashimoto, Y Kamihara, H Horiguchi, S Kikuchi, Y Kawano, K Takada, T Hayashi, K Miyanishi, Yasushi Sato, R Takimoto, M Kobune and J Kato :
A novel strategy inducing autophagic cell death in Burkitt's lymphoma cells with anti-CD19-targeted liposomal rapamycin.,
Blood Cancer Journal, Vol.4, e180, 2014.

(要約): Relapsed or refractory Burkitt's lymphoma often has a poor prognosis in spite of intensive chemotherapy that induces apoptotic and/or necrotic death of lymphoma cells. Rapamycin (Rap) brings about autophagy, and could be another treatment. Further, anti-CD19-targeted liposomal delivery may enable Rap to kill lymphoma cells specifically. Rap was encapsulated by anionic liposome and conjugated with anti-CD19 antibody (CD19-GL-Rap) or anti-CD2 antibody (CD2-GL-Rap) as a control. A fluorescent probe Cy5.5 was also liposomized in the same way (CD19 or CD2-GL-Cy5.5) to examine the efficacy of anti-CD19-targeted liposomal delivery into CD19-positive Burkitt's lymphoma cell line, SKW6.4. CD19-GL-Cy5.5 was more effectively uptaken into SKW6.4 cells than CD2-GL-Cy5.5 in vitro. When the cells were inoculated subcutaneously into nonobese diabetic/severe combined immunodeficiency mice, intravenously administered CD19-GL-Cy5.5 made the subcutaneous tumor fluorescent, while CD2-GL-Cy5.5 did not. Further, CD19-GL-Rap had a greater cytocidal effect on not only SKW6.4 cells but also Burkitt's lymphoma cells derived from patients than CD2-GL-Rap in vitro. The specific toxicity of CD19-GL-Rap was cancelled by neutralizing anti-CD19 antibody. The survival period of mice treated with intravenous CD19-GL-Rap was significantly longer than that of mice treated with CD2-GL-Rap after intraperitoneal inoculation of SKW6.4 cells. Anti-CD19-targeted liposomal Rap could be a promising lymphoma cell-specific treatment inducing autophagic cell death.
(出版サイトへのリンク): ● Publication site (DOI): 10.1038/bcj.2014.2
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24510029; ● Search Scopus @ Elsevier (PMID): 24510029; ● Search Scopus @ Elsevier (DOI): 10.1038/bcj.2014.2

(DOI: 10.1038/bcj.2014.2, PubMed: 24510029) Hideki Ishikawa, Michihiro Mutoh, Sadao Suzuki, Shinkan Tokudome, Yoshihisa Saida, Takashi Abe, Shozo Okamura, Masahiro Tajika, Takashi Joh, Shinji Tanaka, Shin-Ei Kudo, Takahisa Matsuda, Masaki Iimuro, Tomomi Yukawa, Tetsuji Takayama, Yasushi Sato, Kyowon Lee, Shinji Kitamura, Motowo Mizuno, Yasushi Sano, Nobuhisa Gondo, Kenji Sugimoto, Masato Kusunoki, Chiho Goto, Nariaki Matsuura, Toshiyuki Sakai and Keiji Wakabayashi :
The preventive effects of low-dose enteric-coated aspirin tablets on the development of colorectal tumours in Asian patients: a randomised trial.,
Gut, Vol.63, No.11, 1755-1759, 2014.

(要約): Low-dose, enteric-coated aspirin tablets reduced colorectal tumour recurrence in an Asian population. The results are consistent with those obtained from other randomised controlled trials in Western countries. THE CLINICAL TRIAL REGISTRY WEBSITE AND THE CLINICAL TRIAL NUMBER: http://www.umin.ac.jp (number UMIN000000697).
(出版サイトへのリンク): ● Publication site (DOI): 10.1136/gutjnl-2013-305827
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24488498; ● Summary page in Scopus @ Elsevier: 2-s2.0-84893158245

(DOI: 10.1136/gutjnl-2013-305827, PubMed: 24488498, Elsevier: Scopus) Takahiro Osuga, Tsuyoshi Hayashi, Hirotoshi Ishiwatari, Michihiro Ono, Makoto Yoshida, Yasutoshi Kimura, Tadashi Hasegawa, Yasushi Sato, Tsutomu Sato, Koji Miyanishi, Rishu Takimoto, Masayoshi Kobune and Junji Kato :
Pancreatic metastasis from a solitary fibrous tumor of the central nervous system.,
JOP : Journal of the Pancreas, Vol.15, No.1, 58-62, 2014.

(要約): Histological findings and immunohistochemical profile obtained by EUS-FNA are invaluable for the correct diagnosis to avoid excessive surgical procedures.
(キーワード): Biopsy, Fine-Needle / Brain Neoplasms / Chest Pain / Coronary Disease / Diagnosis, Differential / Diagnostic Errors / Diagnostic Imaging / Female / Humans / Incidental Findings / Meningeal Neoplasms / Meningioma / Middle Aged / Neuroendocrine Tumors / Pancreatectomy / Pancreatic Neoplasms / Solitary Fibrous Tumors
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24413787; ● Search Scopus @ Elsevier (PMID): 24413787

(PubMed: 24413787) M Hirakawa, R Takimoto, F Tamura, M Yoshida, M Ono, K Murase, Yasushi Sato, T Osuga, T Sato, S Iyama, K Miyanishi, K Takada, T Hayashi, M Kobune and J Kato :
Fucosylated TGF- receptors transduces a signal for epithelial-mesenchymal transition in colorectal cancer cells.,
British Journal of Cancer, Vol.110, No.1, 156-163, 2013.

(要約): Fucosyltransferase 3/6 has an essential role in cancer cell adhesion to endothelial cells by upregulation of sialyl Lewis antigens and also by enhancement of cancer cell migration through TGF--mediated EMT.
(キーワード): Cell Adhesion / Cell Line, Tumor / Colorectal Neoplasms / Epithelial-Mesenchymal Transition / Fucosyltransferases / HT29 Cells / Humans / Phosphorylation / RNA, Small Interfering / Receptors, Transforming Growth Factor beta / Signal Transduction / Smad Proteins / Transfection / Transforming Growth Factor beta / Up-Regulation
(出版サイトへのリンク): ● Publication site (DOI): 10.1038/bjc.2013.699
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24253505; ● Search Scopus @ Elsevier (PMID): 24253505; ● Search Scopus @ Elsevier (DOI): 10.1038/bjc.2013.699

(DOI: 10.1038/bjc.2013.699, PubMed: 24253505) Kaoru Ono, Tsutomu Sato, Satoshi Iyama, Ayumi Tatekoshi, Akari Hashimoto, Yusuke Kamihara, Hiroto Horiguchi, Shohei Kikuchi, Kohichi Takada, Tsuyoshi Hayashi, Koji Miyanishi, 佐藤康史, Rishu Takimoto, Masayoshi Kobune, Junji Kato :
[Successful treatment with rituximab in a patient with refractory mixed-type autoimmune hemolytic anemia].,
臨床血液, Vol.54, No.11, 2053-2055, 2013年.

(要約): The evidence that rituximab is effective therapy for refractory warm or cold autoimmune hemolytic anemia (AIHA) has been accumulating; however, the efficacy of rituximab for mixed-type AIHA is not evident. Herein, we report a case of mixed-type AIHA refractory to corticosteroids and splenectomy, but successfully treated with rituximab (375 mg/m(2)/day, once weekly, four times). She achieved a complete response, which has been maintained for 16 months, to date, despite steroid tapering. Our case suggests that rituximab therapy should be considered for refractory AIHA even of mixed-type.
(キーワード): Anemia, Hemolytic, Autoimmune / Antibodies, Monoclonal, Murine-Derived / Female / Humans / Remission Induction / Rituximab / Treatment Outcome
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24305538; ● Search Scopus @ Elsevier (PMID): 24305538

(PubMed: 24305538) Yuuki Ikeda, Yasushi Sato, Yuusuke Kamihara, Masahiro Hirakawa, Hiroyuki Onuma, Kohichi Takada, Tsuyoshi Hayashi, Tsutomu Sato, Koji Miyanishi, Rishu Takimoto, Masayoshi Kohune, Takayuki Nobuoka, Hiroko Noguchi, Motoo Oi, Hisato Honma, Kohichi Hirata, Tadashi Hasegawa and Junji Kato :
A case of idiopathic encapsulating peritoneal sclerosis with intractable ileus successfully treated by surgery and steroid therapy.,
Clinical Journal of Gastroenterology, Vol.6, No.4, 295-298, 2013.

(要約): Encapsulating peritoneal sclerosis (EPS) occurring without a history of peritoneal dialysis is rare. We report on a patient with idiopathic EPS following intractable ileus who was successfully treated by surgery and postoperative steroid therapy without any sign of recurrence. A 67-year-old woman was referred to our department for further treatment of intractable ileus. Abdominal CT scanning revealed wall thickening of the proximal jejunum. Double-balloon enteroscopy disclosed stenosis of the jejunum at 20 cm anally from the Treitz ligament, although the intestinal mucosa appeared normal without specific biopsy findings. In addition, FDG-PET showed no abnormal accumulation, thus discounting a malignant lesion. Since conservative therapy failed to improve the ileus, we performed an operation on her in order to release the ileus and make a histological diagnosis. Surgical findings included a whitish thickening of the serosa extending to the intestine and the whole mesentery. Accordingly, we made a diagnosis of idiopathic encapsulating peritoneal sclerosis because of her negative history of peritoneal dialysis, laparotomy or peritonitis, in addition to the above-noted findings. Postoperative oral administration of steroid has suppressed EPS recurrence. In patients with intractable ileus, EPS should be added to the list of differential diagnoses, even if they have not undergone peritoneal dialysis.
(出版サイトへのリンク): ● Publication site (DOI): 10.1007/s12328-013-0395-9
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26181733; ● Search Scopus @ Elsevier (PMID): 26181733; ● Search Scopus @ Elsevier (DOI): 10.1007/s12328-013-0395-9

(DOI: 10.1007/s12328-013-0395-9, PubMed: 26181733) Tsuyoshi Hayashi, Hirotoshi Ishiwatari, Makoto Yoshida, Michihiro Ono, Tsutomu Sato, Koji Miyanishi, Yasushi Sato, Masayoshi Kobune, Rishu Takimoto, Tomoko Mitsuhashi, Hiroko Asanuma, Jiro Ogino, Tadashi Hasegawa, Tomoko Sonoda and Junji Kato :
Rapid on-site evaluation by endosonographer during endoscopic ultrasound-guided fine needle aspiration for pancreatic solid masses.,
Journal of Gastroenterology and Hepatology, Vol.28, No.4, 656-663, 2013.

(要約): This cytological grading system used in ROSE by endosonographers is invaluable for the diagnosis of pancreatic solid masses.
(キーワード): Aged / Carcinoma, Pancreatic Ductal / Early Diagnosis / Endoscopic Ultrasound-Guided Fine Needle Aspiration / Endosonography / Female / Humans / Male / Middle Aged / Neoplasm Grading / Pancreatic Neoplasms / Reproducibility of Results / Retrospective Studies
(出版サイトへのリンク): ● Publication site (DOI): 10.1111/jgh.12122
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23301574; ● Search Scopus @ Elsevier (PMID): 23301574; ● Search Scopus @ Elsevier (DOI): 10.1111/jgh.12122

(DOI: 10.1111/jgh.12122, PubMed: 23301574) Hirakawa Masahiro, Yasushi Sato, Ohnuma Hiroyuki, Tetsuji Takayama, Sagawa Tamotsu, Nobuoka Takayuki, Harada Keisuke, Hiroshi Miyamoto, Sato Yasuhiro, Takahashi Yasuo, Katsuki Shinichi, Hirayama Michiaki, Takahashi Minoru, Ono Michihiro, Maeda Masahiro, Takada Kohichi, Hayashi Tsuyoshi, Sato Tsutomu, Miyanishi Koji, Takimoto Rishu, Kobune Masayoshi, Hirata Koichi and Kato Junji :
A phase II study of neoadjuvant combination chemotherapy with docetaxel, cisplatin,and S-1 for locally advanced resectable gastric cancer: nucleotide excision repair (NER) as potential chemoresistance marker,
Cancer Chemotherapy and Pharmacology, Vol.71, No.3, 789-797, 2013.

(要約): The combination of docetaxel, cisplatin, and S-1 (DCS) chemotherapy is expected to be a promising regimen for advanced gastric cancer. This study was performed to evaluate the efficacy and safety of neoadjuvant DCS chemotherapy for locally advanced resectable gastric cancer. Patients with locally advanced gastric cancer received 2 courses of preoperative chemotherapy with S-1 (40 mg/m(2) b.i.d.) on days 1-14 and docetaxel (60 mg/m(2)) plus cisplatin (60 mg/m(2)) on day 8 every 3 weeks, followed by standard curative surgery within 4-8 weeks. The primary endpoint was R0 resectability. Expression of damage DNA binding protein complex subunit 2 (DDB2)/excision repair cross-complementing 1 (ERCC1) in the pretreated tumor tissues was examined by immunohistochemistry. A total of 43 patients received neoadjuvant chemotherapy. The response rate was 74.4%, and disease control ratio was 100%. Grade 4 neutropenia developed in 53.5% of patients and febrile neutropenia in 16.3%. Non-hematological grade 3/4 adverse events were anorexia (23.3%), nausea (14.0%), and diarrhea (23.3%), but these were generally transient and manageable. The proportion of R0 resections in the 43 eligible patients was 90.7%, and a pathological response was found in 65.9% of patients. There were no treatment-related deaths and no major surgical complications. The accuracy of the combination of DDB2 and ERCC1 expression for predicting chemoresistance was 82.5%. Preoperative treatment with DCS combination for locally advanced gastric cancer demonstrated a sufficient R0 resection rate and a good pathological response with manageable toxicities. The DDB2/ERCC1-high phenotype, as determined by immunohistochemistry, may be useful predictor of resistance to DCS chemotherapy.
(キーワード): Adult / Aged / Antimetabolites, Antineoplastic / Antineoplastic Agents / Antineoplastic Agents, Phytogenic / Antineoplastic Combined Chemotherapy Protocols / Biological Markers / Cisplatin / Combined Modality Therapy / DNA Repair / DNA-Binding Proteins / Drug Administration Schedule / Drug Combinations / Drug Resistance, Neoplasm / Endonucleases / Endosonography / Female / Follow-Up Studies / Humans / Kaplan-Meier Estimate / Male / Middle Aged / Neoadjuvant Therapy / Oxonic Acid / Stomach Neoplasms / Survival Analysis / Taxoids / Tegafur / Tomography, X-Ray Computed / Treatment Outcome
(出版サイトへのリンク): ● Publication site (DOI): 10.1007/s00280-013-2073-5
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23338051; ● Search Scopus @ Elsevier (PMID): 23338051; ● Search Scopus @ Elsevier (DOI): 10.1007/s00280-013-2073-5

(DOI: 10.1007/s00280-013-2073-5, PubMed: 23338051) Shingo Tanaka, Koji Miyanishi, Masayoshi Kobune, Yutaka Kawano, Toshifumi Hoki, Tomohiro Kubo, Tsuyoshi Hayashi, Tsutomu Sato, Yasushi Sato, Rishu Takimoto and Junji Kato :
Increased hepatic oxidative DNA damage in patients with nonalcoholic steatohepatitis who develop hepatocellular carcinoma.,
Journal of Gastroenterology, Vol.48, No.11, 1249-1258, 2013.

(要約): The 8-OHdG content in the liver tissue of NASH-HCC patients was significantly different from that in the other patients. The median immunostaining intensity was 8.605 in the NASH-HCC cases, which was significantly higher than that in the cases of NASH without HCC (4.845; P = 0.003). Multivariate analysis using hepatic 8-OHdG content as a factor in addition to age and fasting blood sugar revealed a significant difference in clinicopathological factors between NASH-HCC and NASH without HCC cases. Old age (P = 0.015) and high relative immunostaining intensity for intrahepatic 8-OHdG (P = 0.037) were identified as independent factors.
(キーワード): Adult / Aged / Aged, 80 and over / Aldehydes / Carcinoma, Hepatocellular / Cell Transformation, Neoplastic / 酸化DNA傷害 (oxidative DNA damage) / DNA, Neoplasm / Deoxyguanosine / Fatty Liver / Female / Humans / Liver / Liver Neoplasms / Male / Middle Aged / Neoplasm Staging / Non-alcoholic Fatty Liver Disease / 酸化ストレス (oxidative stress) / Young Adult
(出版サイトへのリンク): ● Publication site (DOI): 10.1007/s00535-012-0739-0
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23329365; ● Search Scopus @ Elsevier (PMID): 23329365; ● Search Scopus @ Elsevier (DOI): 10.1007/s00535-012-0739-0

(DOI: 10.1007/s00535-012-0739-0, PubMed: 23329365) Sho Takahashi, Michiaki Hirayama, Ganji Kuroiwa, Yutaka Kawano, Kohichi Takada, Tsutomu Sato, Koji Miyanishi, Yasushi Sato, Rishu Takimoto, Masayoshi Kobune and Junji Kato :
Diagnostic validity of CT gastrography versus gastroscopy for primary lesions in gastric cancer: evaluating the response to chemotherapy, a retrospective analysis.,
Gastric Cancer, Vol.16, No.4, 543-548, 2012.

(要約): There was good concordance between the evaluations of GS and CT gastrography. CT gastrography exhibited favorable results in accuracy as well as 100 % PD predictability, which implied the possibility of using CT gastrography as a substitute for endoscopic assessments at post-chemotherapy assessments.
(キーワード): Aged / Aged, 80 and over / Antineoplastic Combined Chemotherapy Protocols / Cisplatin / Drug Combinations / Female / Follow-Up Studies / Gastroscopy / Humans / Lymphatic Metastasis / Male / Middle Aged / Neoplasm Staging / Oxonic Acid / Paclitaxel / Prognosis / Retrospective Studies / Stomach Neoplasms / Taxoids / Tegafur / Tomography, X-Ray Computed / Validation Studies as Topic
(出版サイトへのリンク): ● Publication site (DOI): 10.1007/s10120-012-0217-7
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23187880; ● Search Scopus @ Elsevier (PMID): 23187880; ● Search Scopus @ Elsevier (DOI): 10.1007/s10120-012-0217-7

(DOI: 10.1007/s10120-012-0217-7, PubMed: 23187880) Hirotoshi Ishiwatari, Yasushi Sato, Kazuyuki Murase, Akihiro Yoneda, Ryosuke Fujita, Hiroki Nishita, Kubo Naoko Birukawa, Tsuyoshi Hayashi, Tsutomu Sato, Koji Miyanishi, Rishu Takimoto, Masayoshi Kobune, Shigenori Ota, Yasutoshi Kimura, Koichi Hirata, Junji Kato and Yoshiro Niitsu :
Treatment of pancreatic fibrosis with siRNA against a collagen-specific chaperone in vitamin A-coupled liposomes.,
Gut, Vol.62, No.9, 1328-1339, 2012.

(要約): These data suggest the therapeutic potential of the present approach for reversing pancreatic fibrosis.
(キーワード): Animals / Ceruletide / コラーゲン (collagen) / Fibrosis / Gastrointestinal Agents / HSP47 Heat-Shock Proteins / Humans / Immunosuppressive Agents / リポソーム (liposomes) / Male / Models, Animal / Organotin Compounds / Pancreas / Pancreatitis, Chronic / RNA, Small Interfering / Rats / Rats, Inbred Lew / Rats, Wistar / Treatment Outcome / ビタミンA (vitamin A) / Vitamins
(出版サイトへのリンク): ● Publication site (DOI): 10.1136/gutjnl-2011-301746
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23172890; ● Search Scopus @ Elsevier (PMID): 23172890; ● Search Scopus @ Elsevier (DOI): 10.1136/gutjnl-2011-301746

(DOI: 10.1136/gutjnl-2011-301746, PubMed: 23172890) M Kobune, S Iyama, S Kikuchi, H Horiguchi, T Sato, K Murase, Y Kawano, K Takada, K Ono, Y Kamihara, T Hayashi, K Miyanishi, Yasushi Sato, R Takimoto and J Kato :
Stromal cells expressing hedgehog-interacting protein regulate the proliferation of myeloid neoplasms.,
Blood Cancer Journal, Vol.2, 2012.

(要約): Aberrant reactivation of hedgehog (Hh) signaling has been described in a wide variety of human cancers including cancer stem cells. However, involvement of the Hh-signaling system in the bone marrow (BM) microenvironment during the development of myeloid neoplasms is unknown. In this study, we assessed the expression of Hh-related genes in primary human CD34(+) cells, CD34(+) blastic cells and BM stromal cells. Both Indian Hh (Ihh) and its signal transducer, smoothened (SMO), were expressed in CD34(+) acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS)-derived cells. However, Ihh expression was relatively low in BM stromal cells. Remarkably, expression of the intrinsic Hh-signaling inhibitor, human Hh-interacting protein (HHIP) in AML/MDS-derived stromal cells was markedly lower than in healthy donor-derived stromal cells. Moreover, HHIP expression levels in BM stromal cells highly correlated with their supporting activity for SMO(+) leukemic cells. Knockdown of HHIP gene in stromal cells increased their supporting activity although control cells marginally supported SMO(+) leukemic cell proliferation. The demethylating agent, 5-aza-2'-deoxycytidine rescued HHIP expression via demethylation of HHIP gene and reduced the leukemic cell-supporting activity of AML/MDS-derived stromal cells. This indicates that suppression of stromal HHIP could be associated with the proliferation of AML/MDS cells.
(出版サイトへのリンク): ● Publication site (DOI): 10.1038/bcj.2012.36
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22961059; ● Search Scopus @ Elsevier (PMID): 22961059; ● Search Scopus @ Elsevier (DOI): 10.1038/bcj.2012.36

(DOI: 10.1038/bcj.2012.36, PubMed: 22961059) Satoshi Iyama, Tsutomu Sato, Kazuyuki Murase, Yusuke Kamihara, Kaoru Ono, Shohei Kikuchi, Kohichi Takada, Koji Miyanishi, Yasushi Sato, Rishu Takimoto, Masayoshi Kobune and Junji Kato :
Intermittent administration of recombinant human soluble thrombomodulin successfully controlled chronic disseminated intravascular coagulation in a patient with dissecting aortic aneurysm on an outpatient basis.,
Blood Coagulation & Fibrinolysis, Vol.23, No.6, 548-550, 2012.

(要約): Chronic disseminated intravascular coagulation (DIC) is a rare but life-threatening complication of dissecting aortic aneurysm. Although anticoagulant therapy may often proves effective for controlling DIC itself, patients would have to be hospitalized for a long period due to continuous infusion therapy. Subcutaneous injection of a highly concentrated preparation of heparin calcium may offer one alternative treatment for DIC; however, daily subcutaneous use of heparin for the treatment of DIC has impaired quality of life (QOL). The other alternative therapy is intravenous administration of recombinant human soluble thrombomodulin (rTM), which includes the active extracellular domain of thrombomodulin. Reportedly, rTM effectively resolves DIC by only 6 consecutive days of administration; however, how frequently rTM should be administered after the resolution of chronic DIC to have good control of it has been unclear. We report herein a case of chronic DIC complicated with dissecting aortic aneurysm, whose resolution of chronic DIC achieved by 6 consecutive days of rTM has been maintained by once a week administration of rTM on an outpatient basis.
(キーワード): Administration, Intravenous / Ambulatory Care / Aneurysm, Dissecting / Aortic Aneurysm / Chronic Disease / Disseminated Intravascular Coagulation / Drug Administration Schedule / Female / Humans / Middle Aged / Multidetector Computed Tomography / Recombinant Proteins / Thrombomodulin
(出版サイトへのリンク): ● Publication site (DOI): 10.1097/MBC.0b013e32835510d6
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22732250; ● Search Scopus @ Elsevier (PMID): 22732250; ● Search Scopus @ Elsevier (DOI): 10.1097/MBC.0b013e32835510d6

(DOI: 10.1097/MBC.0b013e32835510d6, PubMed: 22732250) Satoshi Iyama, Tsutomu Sato, Kazuyuki Murase, Shohei Kikuchi, Yusuke Kamihara, Kaoru Ono, Kohichi Takada, Koji Miyanishi, Yasushi Sato, Rishu Takimoto, Masayoshi Kobune, Takuro Obama, Masahiro Miyajima, Atsushi Watanabe, Tetsuya Higami, Yasuo Hirayama and Junji Kato :
Successful treatment by fibrin glue sealant for pneumothorax with chronic GVHD resistant to autologous blood patch pleurodesis.,
Internal Medicine, Vol.51, No.15, 2011-2014, 2012.

(要約): Pneumothorax associated with chronic graft-versus-host disease (cGVHD) after stem cell transplantation is a rare complication. Autologous blood has been used successfully for pleurodesis, which was less toxic than chemical agents. However, when pneumothorax is resistant to pleurodesis, no other procedure is more effective and conservative. Here, we describe a case of myelodysplastic syndromes complicated with cGVHD-related pneumothorax. His pneumothorax has been resistant to pleurodesis using autologous blood and was treated successfully with fibrin glue sealant. In our limited experience, we believe the best success could be achieved when this method is used to treat persistent pneumothorax with cGVHD.
(キーワード): Anemia, Refractory, with Excess of Blasts / Blood / Bone Marrow Transplantation / Fibrin Tissue Adhesive / Graft vs Host Disease / Humans / Male / Pleurodesis / Pneumothorax / Tissue Adhesives / Young Adult
(出版サイトへのリンク): ● Publication site (DOI): 10.2169/internalmedicine.51.7355
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22864128; ● Search Scopus @ Elsevier (PMID): 22864128; ● Search Scopus @ Elsevier (DOI): 10.2169/internalmedicine.51.7355

(DOI: 10.2169/internalmedicine.51.7355, PubMed: 22864128) Makoto Yoshida, Rishu Takimoto, Kazuyuki Murase, Yasushi Sato, Masahiro Hirakawa, Fumito Tamura, Tsutomu Sato, Satoshi Iyama, Takahiro Osuga, Koji Miyanishi, Kohichi Takada, Tsuyoshi Hayashi, Masayoshi Kobune and Junji Kato :
Targeting anticancer drug delivery to pancreatic cancer cells using a fucose-bound nanoparticle approach.,
PLoS ONE, Vol.7, No.7, 2012.

(要約): Owing to its aggressiveness and the lack of effective therapies, pancreatic ductal adenocarcinoma has a dismal prognosis. New strategies to improve treatment and survival are therefore urgently required. Numerous fucosylated antigens in sera serve as tumor markers for cancer detection and evaluation of treatment efficacy. Increased expression of fucosyltransferases has also been reported for pancreatic cancer. These enzymes accelerate malignant transformation through fucosylation of sialylated precursors, suggesting a crucial requirement for fucose by pancreatic cancer cells. With this in mind, we developed fucose-bound nanoparticles as vehicles for delivery of anticancer drugs specifically to cancer cells. L-fucose-bound liposomes containing Cy5.5 or Cisplatin were effectively delivered into CA19-9 expressing pancreatic cancer cells. Excess L-fucose decreased the efficiency of Cy5.5 introduction by L-fucose-bound liposomes, suggesting L-fucose-receptor-mediated delivery. Intravenously injected L-fucose-bound liposomes carrying Cisplatin were successfully delivered to pancreatic cancer cells, mediating efficient tumor growth inhibition as well as prolonging survival in mouse xenograft models. This modality represents a new strategy for pancreatic cancer cell-targeting therapy.
(キーワード): Adenocarcinoma / Animals / Antineoplastic Agents / Biomarkers, Tumor / Carbocyanines / Cell Line, Tumor / Cell Transformation, Neoplastic / Cisplatin / Drug Delivery Systems / Female / Fucose / Fucosyltransferases / Gene Expression Regulation, Neoplastic / Humans / リポソーム (liposomes) / Mice / Mice, Nude / ナノ粒子 (nanoparticles) / Pancreatic Neoplasms / Receptors, Cell Surface / Survival Rate / Xenograft Model Antitumor Assays
(出版サイトへのリンク): ● Publication site (DOI): 10.1371/journal.pone.0039545
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22808043; ● Search Scopus @ Elsevier (PMID): 22808043; ● Search Scopus @ Elsevier (DOI): 10.1371/journal.pone.0039545

(DOI: 10.1371/journal.pone.0039545, PubMed: 22808043) Shohei Kikuchi, Masayoshi Kobune, Satoshi Iyama, Tsutomu Sato, Kazuyuki Murase, Yutaka Kawano, Kohichi Takada, Kaoru Ono, Yumiko Kaneko, Koji Miyanishi, Yasushi Sato, Tsuyoshi Hayashi, Rishu Takimoto and Junji Kato :
Improvement of iron-mediated oxidative DNA damage in patients with transfusion-dependent myelodysplastic syndrome by treatment with deferasirox.,
Free Radical Biology and Medicine, Vol.53, No.4, 643-648, 2012.

(要約): Myelodysplastic syndrome (MDS) is characterized by dysplastic and ineffective hematopoiesis, peripheral blood cytopenias, and a risk of leukemic transformation. Most MDS patients eventually require red blood cell (RBC) transfusions for anemia and consequently develop iron overload. Excess free iron in cells catalyzes generation of reactive oxygen species that cause oxidative stress, including oxidative DNA damage. However, it is uncertain how iron-mediated oxidative stress affects the pathophysiology of MDS. This study included MDS patients who visited our university hospital and affiliated hospitals (n=43). Among them, 13 patients received iron chelation therapy when their serum ferritin (SF) level was greater than 1000 ng/mL or they required more than 20 RBC transfusions (or 100 mL/kg of RBC). We prospectively analyzed 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in peripheral blood mononuclear cells (PBMC) obtained from MDS patients before and after iron chelator, deferasirox, administration. We showed that the 8-OHdG levels in MDS patients were significantly higher than those in healthy volunteers and were positively correlated with SF and chromosomal abnormalities. Importantly, the 8-OHdG levels in PBMC of MDS patients significantly decreased after deferasirox administration, suggesting that iron chelation reduced oxidative DNA damage. Thus, excess iron could contribute to the pathophysiology of MDS and iron chelation therapy could improve the oxidative DNA damage in MDS patients.
(キーワード): Antigens, CD / Benzoates / Case-Control Studies / DNA Damage / Deoxyguanosine / Erythrocyte Transfusion / Ferritins / Genome, Human / Humans / Iron Chelating Agents / Iron Overload / Leukocytes, Mononuclear / Myelodysplastic Syndromes / Prospective Studies / 活性酸素 (reactive oxygen species) / Statistics, Nonparametric / Triazoles
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.freeradbiomed.2012.06.006
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22705364; ● Search Scopus @ Elsevier (PMID): 22705364; ● Search Scopus @ Elsevier (DOI): 10.1016/j.freeradbiomed.2012.06.006

(DOI: 10.1016/j.freeradbiomed.2012.06.006, PubMed: 22705364) Shohei Kikuchi, Masayoshi Kobune, Satoshi Iyama, Tsutomu Sato, Kazuyuki Murase, Yutaka Kawano, Kohichi Takada, Kaoru Ono, Tsuyoshi Hayashi, Koji Miyanishi, Yasushi Sato, Rishu Takimoto and Junji Kato :
Prognostic significance of serum ferritin level at diagnosis in myelodysplastic syndrome.,
International Journal of Hematology, Vol.95, No.5, 527-534, 2012.

(要約): Myelodysplastic syndrome (MDS) is characterized by peripheral blood cytopenias and risk of progression to acute myeloid leukemia. Elevated serum ferritin (SF), due to ineffective erythropoiesis and increased iron absorption from the gut, is often observed in non-transfused MDS patients, suggesting involvement of iron overload in its pathogenesis. However, the prognostic value of the baseline SF is unclear. We evaluated baseline SF levels in non-transfused MDS patients. The SF level was significantly higher in the 47 MDS patients in this study than in the healthy controls (P < 0.001). The SF level of higher-risk MDS patients (int-2/high) was significantly higher than that of the lower-risk MDS patients (low/int-1) (467 ± 354 vs. 277 ± 372 ng/ml, P < 0.001). The SF level in MDS patients with chromosomal abnormality was significantly higher than that in patients with normal karyotype. When patients were divided into the low SF group (<500 ng/ml) and high SF group (500 ng/mL), the survival time was significantly longer in the former group than the latter group (118.8 vs. 10.2 M, P = 0.002). Further, leukemia-free survival (LFS) was significantly longer in the low SF group than the high SF group (P = 0.010). Baseline SF level may, therefore, be a prognostic factor for overall survival and LFS in MDS patients.
(キーワード): Adult / Aged / Aged, 80 and over / Female / Ferritins / Follow-Up Studies / Humans / Leukemia, Myeloid, Acute / Male / Middle Aged / Myelodysplastic Syndromes / Prognosis / Retrospective Studies
(出版サイトへのリンク): ● Publication site (DOI): 10.1007/s12185-012-1048-3
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22407873; ● Search Scopus @ Elsevier (PMID): 22407873; ● Search Scopus @ Elsevier (DOI): 10.1007/s12185-012-1048-3

(DOI: 10.1007/s12185-012-1048-3, PubMed: 22407873) Takeuchi Hisashi, Tetsuo Kimura, Koichi Okamoto, Aoyagi Eriko, Hiroshi Miyamoto, Masako Kaji, Hidetaka Takenaka, Seisuke Okamura, Yasushi Sato, Kato Junji, Toshiya Okahisa and Tetsuji Takayama :
A mechanism for abnormal angiogenesis in human radiation proctitis: analysis of expression profile for angiogenic factors,
Journal of Gastroenterology, Vol.47, No.1, 56-64, 2012.

(要約): Radiation proctitis is an increasingly prevalent problem, with many patients being treated with radiotherapy for pelvic cancers. However, the mechanisms by which radiation proctitis develops in humans are not well understood. In this study, the expression profiles of angiogenic factors were analyzed to clarify their role in the etiology of radiation proctitis. Rectal biopsies were taken from 8 patients with radiation proctitis and 8 normal subjects. Protein lysates of the tissues were applied to an antibody array for angiogenesis-related factors. The mRNA level of each factor was evaluated by Taqman real-time PCR. Immunohistochemistry was performed using the labeled streptavidin biotin method. Antibody array analysis revealed 2.12- to 7.31-fold higher expression levels of angiogenin, fibroblast growth factor 1 (FGF1), endoglin, matrix metalloproteinase (MMP)-8, urokinase-type plasminogen activator (uPA) and maspin in radiation proctitis tissues compared with normal rectal mucosa. The mRNA level of each factor in radiation proctitis tissue was significantly higher than in normal rectal mucosa, suggesting their transcriptional activation. Immunohistochemical staining showed strong expression of angiogenin and maspin in rectal epithelia, MMP-8 and uPA in infiltrating lymphocytes, FGF1 in fibroblasts and endoglin in endothelial cells. The expression of VEGF was not evident. Our results suggest that in radiation proctitis, MMP-8 and uPA cooperatively degrade the extracellular matrix and basement membrane to provide space for angiogenesis. Simultaneously, angiogenin and FGF1 promote endothelial cell proliferation, and endoglin induces vessel formation, culminating in angiogenesis. Inhibitors of angiogenic factors such as angiogenin and FGF1 may be effective for treating radiation proctitis.
(キーワード): Aged / Case-Control Studies / Extracellular Matrix / Female / Fibroblast Growth Factor 1 / Gene Expression Regulation / Humans / Male / Matrix Metalloproteinase 8 / Middle Aged / Neovascularization, Pathologic / Pelvic Neoplasms / Polymerase Chain Reaction / Proctitis / RNA, Messenger / Radiation Injuries / Ribonuclease, Pancreatic / Urokinase-Type Plasminogen Activator
(出版サイトへのリンク): ● Publication site (DOI): 10.1007/s00535-011-0470-2
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22081051; ● CiNii @ 国立情報学研究所 (CRID): 1573387450550673408; ● Search Scopus @ Elsevier (PMID): 22081051; ● Search Scopus @ Elsevier (DOI): 10.1007/s00535-011-0470-2

(DOI: 10.1007/s00535-011-0470-2, PubMed: 22081051, CiNii: 1573387450550673408) Tsuyoshi Hayashi, Hirotoshi Ishiwatari, Makoto Yoshida, Tsutomu Sato, Koji Miyanishi, Yasushi Sato, Masayoshi Kobune, Rishu Takimoto, Tomoko Sonoda and Junji Kato :
A phase I trial of arterial infusion chemotherapy with gemcitabine and 5-fluorouracil for unresectable biliary tract cancer.,
International Journal of Clinical Oncology, Vol.17, No.5, 491-497, 2011.

(要約): This regimen of gemcitabine and 5-fluorouracil is tolerable and warrants further investigation in biliary tract cancer.
(キーワード): Aged / Aged, 80 and over / Antineoplastic Combined Chemotherapy Protocols / Biliary Tract Neoplasms / Cohort Studies / Deoxycytidine / Dose-Response Relationship, Drug / Drug Administration Schedule / Fluorouracil / Humans / Infusions, Parenteral / Male / Middle Aged / Treatment Outcome
(出版サイトへのリンク): ● Publication site (DOI): 10.1007/s10147-011-0320-5
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21932164; ● Search Scopus @ Elsevier (PMID): 21932164; ● Search Scopus @ Elsevier (DOI): 10.1007/s10147-011-0320-5

(DOI: 10.1007/s10147-011-0320-5, PubMed: 21932164) Hirotoshi Ishiwatari, Tsuyoshi Hayashi, Makoto Yoshida, Wataru Jomen, Koji Miyanishi, Tsutomu Sato, Yasushi Sato, Rishu Takimoto, Masayoshi Kobune and Junji Kato :
A case of pancreatic abscess associated with colonic fistula successfully treated by endoscopic transgastric drainage using a metallic stent.,
Clinical Journal of Gastroenterology, Vol.4, No.5, 331-335, 2011.

(要約): A 64-year-old man, who had been treated conservatively for acute pancreatitis in another hospital 6 months previously, was admitted to our hospital with abdominal pain and fever. CT scan showed an air-containing fluid collection extending from the pancreatic tail to areas around the descending colon, leading to a diagnosis of pancreatic abscess associated with colonic fistula. We performed EUS-guided placement of a naso-cystic tube and an internal drainage tube stent, through which irrigation with saline was started. Because these tubes did not effectively relieve the symptoms, a covered EMS was placed to facilitate drainage to the stomach. Both the symptoms and signs of infection improved, and a contrast study confirmed disappearance of the abscess and closure of the fistula. He has been well without recurrence of the pancreatic abscess for half a year.
(出版サイトへのリンク): ● Publication site (DOI): 10.1007/s12328-011-0249-2
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26189634; ● Search Scopus @ Elsevier (PMID): 26189634; ● Search Scopus @ Elsevier (DOI): 10.1007/s12328-011-0249-2

(DOI: 10.1007/s12328-011-0249-2, PubMed: 26189634) Sho Takahashi, 佐藤康史, Tamotsu Sagawa, Shingo Tanaka, Kazuyuki Murase, Kohichi Takada, Satoshi Iyama, Tsutomu Sato, Rishu Takimoto, Masayoshi Kobune, Ganji Kuroiwa, Michiaki Hirayama, Tetsuro Okamoto, Junji Kato :
A case of ulcerative colitis accompanied with myelodysplastic syndrome successfully treated by cyclosporine.,
日本消化器病学会雑誌, Vol.108, No.8, 1405-1412, 2011年.

(要約): A 64-year-old man had been admitted to a previous hospital because of melena and a diagnosis of ulcerative colitis (UC, pancolitis type) had been made. He had received prednisolone and 5-ASA but steroid-induced hyperamylasemia had developed. Prednisolone had been tapered and halted, but it had resulted in UC relapse and thrombocytopenia. Then, he was referred to our hospital due to severe melena with hypovolemic shock. However, he was also positive for CMV antigen. Thus, we attempted to treat him with ganciclovir for CMV and intravenous cyclosporine (CsA) for UC. According to his clinical course, a reduction of CsA blood concentration induced leukocytopenia. Myelodysplastic syndrome (MDS, RAEB-1) was then revealed after bone marrow biopsy. A high blood CsA concentration may cause the improvement of UC and MDS conditions.
(キーワード): Colitis, Ulcerative / Cyclosporine / Humans / Immunosuppressive Agents / Male / Middle Aged / Myelodysplastic Syndromes
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21817844; ● Search Scopus @ Elsevier (PMID): 21817844

(PubMed: 21817844) Tsutomu Sato, Masayoshi Kobune, Kazuyuki Murase, Yukari Kado, Tetsuro Okamoto, Shingo Tanaka, Shohei Kikuchi, Hiroyuki Nagashima, Yutaka Kawano, Kohichi Takada, Satoshi Iyama, Koji Miyanishi, Yasushi Sato, Rishu Takimoto and Junji Kato :
Iron chelator deferasirox rescued mice from Fas-induced fulminant hepatitis.,
Hepatology Research, Vol.41, No.7, 660-667, 2011.

(要約): These findings indicated that the iron chelation exerted a hepatoprotective effect by scavenging ROS upstream of caspase-3 and that iron chelation with deferasirox is a potential treatment for patients with fulminant hepatitis.
(出版サイトへのリンク): ● Publication site (DOI): 10.1111/j.1872-034X.2011.00821.x
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21711425; ● Search Scopus @ Elsevier (PMID): 21711425; ● Search Scopus @ Elsevier (DOI): 10.1111/j.1872-034X.2011.00821.x

(DOI: 10.1111/j.1872-034X.2011.00821.x, PubMed: 21711425) Tsutomu Sato, Satoshi Iyama, Kazuyuki Murase, Yusuke Kamihara, Kaoru Ono, Shohei Kikuchi, Kohichi Takada, Koji Miyanishi, Yasushi Sato, Rishu Takimoto, Masayoshi Kobune and Junji Kato :
Novel missense mutation in the TMPRSS6 gene in a Japanese female with iron-refractory iron deficiency anemia.,
International Journal of Hematology, Vol.94, No.1, 101-103, 2011.

(要約): Iron-refractory iron deficiency anemia (IRIDA) is a rare autosomal-recessive disorder hallmarked by hypochromic microcytic anemia, low transferrin saturation, and unresponsiveness to oral iron with partial recovery after parenteral iron administration. The disease is caused by mutations in TMPRSS6 (transmembrane protease serine 6) that prevent inactivation of membrane-bound hemojuvelin, an activator of hepcidin transcription. To date, 38 cases have been characterized and reported in European countries and the United States. In this paper, we describe the first case of a Japanese female with IRIDA, who carried a novel mutation (K253E) in the CUB (complement factor C1r/C1s, urchin embryonic growth factor and bone morphogenetic protein 1) domain of the TMPRSS6 gene.
(キーワード): Adult / Anemia, Iron-Deficiency / Asian Continental Ancestry Group / Drug Resistance / Female / Humans / Iron / Membrane Proteins / Mutation, Missense / Rare Diseases / Serine Endopeptidases / Treatment Outcome
(出版サイトへのリンク): ● Publication site (DOI): 10.1007/s12185-011-0881-0
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21643693; ● Search Scopus @ Elsevier (PMID): 21643693; ● Search Scopus @ Elsevier (DOI): 10.1007/s12185-011-0881-0

(DOI: 10.1007/s12185-011-0881-0, PubMed: 21643693) Masayoshi Kobune, Koji Miyanishi, Kohichi Takada, Yutaka Kawano, Hiroyuki Nagashima, Shohei Kikuchi, Kazuyuki Murase, Satoshi Iyama, Tsutomu Sato, Yasushi Sato, Rishu Takimoto and Junji Kato :
Establishment of a simple test for iron absorption from the gastrointestinal tract.,
International Journal of Hematology, Vol.93, No.6, 715-719, 2011.

(要約): Recent studies on iron metabolism have begun to reveal the molecular mechanisms underlying iron absorption, which is dramatically affected in several disorders. In the clinical setting, the ability to determine the status of iron absorption would aid in the diagnosis of pathological conditions. Efforts to develop an oral iron absorption test (OIAT) date back to at least 60 years. However, previous procedures were associated with a number of problems, such as radiation exposure and low reproducibility. In an attempt to resolve these issues, we employed sodium ferrous citrate (SFC), by which the influence of various nutrients and drugs on iron absorption was markedly reduced. We found that OIAT using SFC was simple to perform in both hospitalized patients and outpatients. The increment of serum iron and % transferrin saturation at 120 min after SFC administration was useful in distinguishing iron absorption between healthy volunteers, patients with iron-deficiency anemia, and patients with anemia secondary to chronic disorders, which are respectively characterized by normal, enhanced, and reduced iron absorption. Thus, the SFC-based OIAT may represent a viable screening test for the evaluation of gastrointestinal iron absorption.
(キーワード): Adult / Anemia, Iron-Deficiency / Blood Chemical Analysis / Chronic Disease / Female / Ferrous Compounds / Gastrointestinal Tract / Humans / Intestinal Absorption / Iron / Male / Middle Aged / Young Adult
(出版サイトへのリンク): ● Publication site (DOI): 10.1007/s12185-011-0878-8
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21626456; ● Search Scopus @ Elsevier (PMID): 21626456; ● Search Scopus @ Elsevier (DOI): 10.1007/s12185-011-0878-8

(DOI: 10.1007/s12185-011-0878-8, PubMed: 21626456) Tetsuji Takayama, Hiroyuki Nagashima, Masahiro Maeda, Shuichi Nojiri, Michiaki Hirayama, Yoichiro Nakano, Yasuo Takahashi, Yasushi Sato, Hitoshi Sekikawa, Mitsuru Mori, Tomoko Sonoda, Tetsuo Kimura, Junji Kato and Yoshiro Niitsu :
Randomized double-blind trial of sulindac and etodolac to eradicate aberrant crypt foci and to prevent sporadic colorectal polyps.,
Clinical Cancer Research, Vol.17, No.11, 3803-3811, 2011.

(要約): On the basis of the results of our preliminary trial suggesting that aberrant crypt foci (ACF) could be eradicated by short-term administration of sulindac, in the present study, we explored the feasibility of using ACF as surrogate markers for chemoprevention of colorectal cancer. Experimental design: Randomly assigned to sulindac (300 mg daily), etodolac (400 mg daily), and placebo groups were 189 subjects without polyps or who had undergone polypectomy. Drugs were administered for 2 months. ACF in the rectal region were counted by magnifying endoscopy. Occurrence of polyps was evaluated at 12 months. A planned interim analysis was conducted. ACF number at 2 months was significantly suppressed in the sulindac group (P = 0.0075), but not in the etodolac group (P = 0.73). In the sulindac group, the numbers of adenomas plus hyperplastic polyps (total polyps) and adenomas at 12 months were significantly (P = 0.02) and marginally (P = 0.064) lower, respectively, in comparison with the placebo group; no such difference was observed in the etodolac group. In analysis of only polypectomized subjects, the numbers of total polyps and adenomas in the sulindac group were even more markedly lower, with P values of 0.014 and 0.034, respectively. A similar tendency was confirmed by analyses of the incidence of polyps at 12 months. Suppression rates of total polyps and adenomas in ACF responders to sulindac were significantly greater than in nonresponders. In all groups, compliance was more than 90% and no intolerable adverse effects were observed. ACF may be useful as surrogate lesions for chemoprevention of colorectal cancer.
(キーワード): Aberrant Crypt Foci / Adenoma / Aged / Aged, 80 and over / Antineoplastic Combined Chemotherapy Protocols / Colonic Polyps / Colorectal Neoplasms / Etodolac / Female / Humans / Male / Middle Aged / Sulindac
(出版サイトへのリンク): ● Publication site (DOI): 10.1158/1078-0432.CCR-10-2395
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21385928; ● Search Scopus @ Elsevier (PMID): 21385928; ● Search Scopus @ Elsevier (DOI): 10.1158/1078-0432.CCR-10-2395

(DOI: 10.1158/1078-0432.CCR-10-2395, PubMed: 21385928) Masahiro Hirakawa, 佐藤康史, Hiroyuki Ohnuma, Tamotsu Sagawa, Hirotoshi Ishiwatari, Kazuyuki Murase, Satoshi Iyama, Tsuyoshi Hayashi, Tsutomu Sato, Koji Miyanishi, Masayoshi Kobune, Rishu Takimoto, Junji Kato :
[Tuberculous pleuritis with onset of refractory pleural effusion after chemoradiotherapy for esophageal cancer].,
日本消化器病学会雑誌, Vol.108, No.2, 231-237, 2011年.

(要約): A 75-year-old man received chemoradiotherapy (CRT) for stage IVa esophageal cancer and complete response (CR) was obtained. However, he was referred to our department for recurrence in an area of esophagus not included in the previously irradiated field. Left pleural effusion increased after admission. Tuberculous pleuritis was eventually diagnosed by thoracoscopic pleural biopsy. It is necessary to accurately diagnose the cause of pleural effusion after CRT, because treatment strategies greatly depend on it. It is also necessary to consider the possible onset of tuberculous pleuritis, in particular, in patients with a history of tuberculosis infection.
(キーワード): Aged / Combined Modality Therapy / Esophageal Neoplasms / Humans / Male / Pleural Effusion / Tuberculosis, Pleural
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21307627; ● Search Scopus @ Elsevier (PMID): 21307627

(PubMed: 21307627) Yasushi Sato, Tetsuji Takayama, Tamotsu Sagawa, Masahiro Hirakawa, Hiroyuki Ohnuma, Koji Miyanishi, Tsutomu Sato, Rishu Takimoto, Masayoshi Kobune, Koichi Okamoto, Hisashi Takeuchi and Junji Kato :
Argon plasma coagulation treatment of hemorrhagic radiation proctopathy: the optimal settings for application and long-term outcome.,
Gastrointestinal Endoscopy, Vol.73, No.3, 543-549, 2011.

(要約): No standard treatment exists for hemorrhagic radiation proctopathy (HRP). Recently it was reported that argon plasma coagulation (APC) is effective for HRP. However, previous studies documented complications such as ulcers, strictures, and perforations in as many as 20% of APC-treated patients. The aim of this study was to determine the optimal parameters for APC by using swine rectum and to assess the safety and effectiveness of APC in HRP patients. Prospective case series. University teaching hospital. Sixty-five patients with HRP were prospectively enrolled between 2000 and 2010. APC for HRP. Optimal APC parameters, number of treatments, success rate, complications, clinical remissions. APC in swine rectal wall ex vivo was optimal with a 40-W current, 1.2-L/min gas flow rate, and 2-second application, which was sufficient to treat the submucosal telangiectasia but did not adversely affect the muscle layer. Sixty-five patients (46 men, 19 women; median age 72 years) with HRP occurring at a mean of 20 months after radiotherapy were studied. Proctopathy was classified as grade A (mild) in 7 patients (10.8%), grade B (moderate) in 41 (63.1%), and grade C (severe) in 17 (26.2%). The treatment success rate was 98.5% after a median of 2 (range 1-5) APC sessions. The median clinical score for rectal bleeding was significantly decreased after APC (P < .0001), and the hemoglobin level was significantly increased (P < .0001). APC was well tolerated, and no significant side effects or complications occurred. During a mean follow-up of 34.6 months (range 3.6 -121.1 months), 4 patients (6.3%) had minor recurrent rectal bleeding and 60 (93.8%) remained in remission. Nonrandomized study. HRP treatment with optimal APC settings yields a high success rate and long-lasting clinical remission with no significant complications.
(キーワード): Adult / Aged / Aged, 80 and over / Animals / Argon Plasma Coagulation / Female / Gastrointestinal Hemorrhage / Humans / Intestinal Mucosa / Lasers, Gas / Male / Middle Aged / Prospective Studies / Prostatic Neoplasms / Radiation Injuries / Rectum / Statistics, Nonparametric / Swine / Treatment Outcome / Uterine Cervical Neoplasms
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.gie.2010.11.015
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21257166; ● Search Scopus @ Elsevier (PMID): 21257166; ● Search Scopus @ Elsevier (DOI): 10.1016/j.gie.2010.11.015

(DOI: 10.1016/j.gie.2010.11.015, PubMed: 21257166) Ikumi Umeda, Tsuyoshi Hayashi, Hirotoshi Ishiwatari, Makoto Yoshida, Kouji Miyanishi, 佐藤康史, Masayoshi Kofune, Risyu Takimoto, Junji Kato, Makoto Meguro, Kouichi Hirata :
A case of severe acute pancreatitis and ischemic gastropathy caused by acute aortic dissection.,
日本消化器病学会雑誌, Vol.108, No.1, 103-110, 2011年.

(要約): A 49-year-old man presented with chest pain and was given a diagnosis of aortic dissection based on computed tomography (CT) findings. Two days later the dissection reached the origin of the celiac artery and there was poor blood flow from the body to the tail of the pancreas and fundus of the stomach wall. Severe acute pancreatitis developed. Endoscopy showed a near-circumferential gastric ulcer in the gastric cardia and we diagnosed ischemic gastropathy. A fistula between the area of infected pancreatic necrosis and the stomach had formed spontaneously and the necrotic tissue was draining into the stomach. His recovery was uneventful.
(キーワード): Acute Disease / Aneurysm, Dissecting / Aortic Aneurysm, Abdominal / Aortic Aneurysm, Thoracic / Humans / Ischemia / Male / Middle Aged / Pancreatitis / Stomach / Stomach Diseases
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21212601; ● Search Scopus @ Elsevier (PMID): 21212601

(PubMed: 21212601) Yasushi Sato, Michihiro Ono, Tamotsu Sagawa, Rishu Takimoto, Masahiro Hirakawa, Hiroyuki Ohnuma, Tsutomu Sato, Satoshi Iyama, Kazuyuki Murase, Koji Miyanishi, Masayoshi Kobune and Junji Kato :
Endoscopic findings of enteropathy-type T-cell lymphoma by double-balloon enteroscopy and capsule endoscopy.,
Digestive Endoscopy, Vol.22, No.3, 243-245, 2010.

(要約): Enteropathy-type T-cell lymphoma (ETL) is a rare primary intestinal disorder, particularly in Japan, and there have been few reports on the endoscopic findings of the disease. Here we report detailed endoscopic findings of ETL based on double-balloon enteroscopy and capsule endoscopy. Double-balloon enteroscopy and capsule endoscopy may be useful tools for diagnosing and monitoring the effects of therapy in patients with ETL.
(キーワード): Capsule Endoscopy / Diagnosis, Differential / Endoscopes, Gastrointestinal / Endoscopy, Gastrointestinal / Female / Humans / Intestinal Neoplasms / Lymphoma, T-Cell / Middle Aged
(出版サイトへのリンク): ● Publication site (DOI): 10.1111/j.1443-1661.2010.00989.x
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20642619; ● Search Scopus @ Elsevier (PMID): 20642619; ● Search Scopus @ Elsevier (DOI): 10.1111/j.1443-1661.2010.00989.x

(DOI: 10.1111/j.1443-1661.2010.00989.x, PubMed: 20642619) Satoshi Iyama, Kazuyuki Murase, Tsutomu Sato, Shohei Kikuchi, 佐藤康史, Masayoshi Kobune, Risyu Takimoto, Junji Kato :
[Evaluation of the efficacy of liposomal amphotericin B].,
感染症学雑誌, Vol.84, No.2, 182-186, 2010年.

(要約): A retrospective study was performed to evaluate the efficacy and safety of liposomal amphotericin B (L-AMB) in a total of 32 cases who were among patients hospitalized at the Fourth Department of Internal Medicine, Sapooro Medical University from December 2006 to April 2008. Primary diagnoses were hematologic diseases in 87.5% of subjects. The most common hematologic diseases included acute myelogenous leukemia in 50% of the subjects, followed by malignant lymphoma in 12.5% of the subjects. The mean administration period was 14.2 +/- 12.9 days, and the mean cumulative dose was 1,786 +/- 2,181 mg. L-AMB improved 21 of 29 cases (72.4%) with some fungal infections or fever-associated neutropenia. Adverse events occurred in 9 cases to a slight degree, in 7 cases to a moderate degree, and in no case to a severe degree. Hypokalemia and hypercreatininemia were seen in 7 cases (21.9%) and 4 cases (12.5%), respectively, but these adverse reactions were so mild that the treatment did not need to be discontinued. Any adverse reactions for which treatment administration was discontinued were confirmed to have disappeared at the end of the study. These results support the efficacy and safety of L-AMB in accordance with previous foreign reports. It was noteworthy that early use of L-AMB prior to established diagnosis sometimes better therapeutic outcomes. It was also suggested that L-AMB could be safely administered while controlling electrolyte balance, such as serum potassium concentration, with sufficient fluid replacement, including physiological saline infusion. There are limitations in the use of the conventional form of amphotericin B because of its renal toxicity and other reasons. However, L-AMB had fewer side effects, so the agent was considered useful for the treatment of hematologic disease patients who either had mycosis or carried a risk for fungal infection.
(キーワード): Amphotericin B / Female / Humans / Leukemia, Myeloid, Acute / Liposomes / Lymphoma / Male / Retrospective Studies
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20420163; ● Search Scopus @ Elsevier (PMID): 20420163

(PubMed: 20420163) Sho Takahashi, Kohichi Takada, Yutaka Kawano, Koji Miyanishi, Hirotoshi Ishiwatari, Tsuyoshi Hayashi, Tamotsu Sagawa, Tsutomu Sato, 佐藤康史, Rishu Takimoto, Masayoshi Kobune, Ganji Kuroiwa, Michiaki Hirayama, Hirotoshi Tobioka, Kouichi Hirata, Mutsuko Omatsu, Tadashi Hasegawa, Junji Kato :
[Cholangiocarcinoma with bile duct adenoma and hamartoma-like lesion in the bile duct].,
日本消化器病学会雑誌, Vol.107, No.3, 461-469, 2010年.

(要約): A 76-year-old man presented with fever of unknown origin. Diagnostic imaging showed a liver tumor measuring 3cm in maximum dimension. The tumor was subsequently resected, and histopathology showed a moderately differentiated adenocarcinoma. This showed a number of bile ductules with variable amounts of stroma, well circumscribed but not encapsulated, so the lesion was diagnosed as a cholangiocarcinoma. Within the tumor there was also a cholangiolocarcinoma-like lesion. In addition, cystically dilated ductules resembling bile duct hamartoma and bile duct adenoma adjacent to the tumor were found, but with no area of transition among them. In the Glisson's capsule around the tumor, there was also a bile duct hamartoma.
(キーワード): Adenoma / Aged / Bile Duct Neoplasms / Bile Ducts, Intrahepatic / Cholangiocarcinoma / Hamartoma / Humans / Male / Neoplasms, Multiple Primary
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20203450; ● Search Scopus @ Elsevier (PMID): 20203450

(PubMed: 20203450) Hirotoshi Ishiwatari, Tsuyoshi Hayashi, Makoto Yoshida, Ganji Kuroiwa, 佐藤康史, Masayoshi Kobune, Rishu Takimoto, Yasutoshi Kimura, Tadashi Hasegawa, Koichi Hirata, Junji Kato :
[A case of solitary fibrous tumor of the pancreas].,
日本消化器病学会雑誌, Vol.106, No.7, 1078-1085, 2009年.

(要約): A 58-year-old woman without any clinical symptoms had a routine health check-up, during which a mass in the head of the pancreas was detected by US. Abdominal US showed a round, hypoechogenic nodule of the pancreatic head. The tumor measured 3cm in diameter and contained an anechoic area. CT revealed a well-demarcated tumor in the pancreatic head. The tumor was partially enhanced by contrast medium, but the left portion of the tumor, which US had shown to be an anechoic area was not enhanced. Imaging findings suggested an endocrine tumor with cystic changes. A pylorus-preserving pancreatoduodenectomy was performed. The tumor was composed of spindle-shaped cells. There was a typical patternless growth of short fascicles and a short storiform arrangement of cells in the stroma with varying degrees of collagenization. Immunohistochemically, the tumor cells were positive for CD34 and Bcl-2. Based on the light microscopic morphology and immunostaining profile, the tumor was classified as a solitary fibrous tumor (SFT) of the pancreas.
(キーワード): Female / Humans / Middle Aged / Pancreatic Neoplasms / Solitary Fibrous Tumors
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19578317; ● Search Scopus @ Elsevier (PMID): 19578317

(PubMed: 19578317) Masayoshi Kobune, Rishu Takimoto, Kazuyuki Murase, Satoshi Iyama, Tsutomu Sato, Shohei Kikuchi, Yutaka Kawano, Kohji Miyanishi, Yasushi Sato, Yoshiro Niitsu and Junji Kato :
Drug resistance is dramatically restored by hedgehog inhibitors in CD34+ leukemic cells.,
Cancer Science, Vol.100, No.5, 948-955, 2009.

(要約): Aberrant reactivation of hedgehog (Hh) signaling has been described in a wide variety of human cancers and in cancer stem cells. However, the contribution of Hh signaling to leukemic cell regulation has remained unclear. In this study, we assessed the possibility that Hh pathway activation contributes to the survival and drug resistance of cluster of differentiation (CD)34+ leukemia cells. Hh signaling in leukemic cell lines and primary leukemic cells was screened by reverse transcription - polymerase chain reaction (RT-PCR) and a Hh signaling reporter assay. We found that Hh signaling is active in several human acute myeloid leukemia (AML) cells, especially primary CD34+ leukemic cells and cytokine-responsive CD34+ cell lines such as Kasumi-1, Kasumi-3 and TF-1. These CD34+ cells express the downstream effectors glioma-associated oncogene homolog (GLI)1 or GLI2, indicative of active Hh signaling. Moreover, inhibition of Hh signaling with the naturally derived Smoothened antagonist cyclopamine, endogenous Hh inhibitor hedgehog-interacting protein or anti-hedgehog neutralizing antibody induced apoptosis after 48 h of exposure, although these CD34+ cell lines exhibited resistance to cytarabine (Ara-C). In contrast, cyclopamine failed to affect growth or survival in U937 and HL-60 cell lines that lack expression of Hh receptor components, confirming that the effect of Hh inhibition is specific. Furthermore, combination with 10 microM cyclopamine significantly reduced drug resistance of CD34+ cell lines and primary CD34+ leukemic cells to Ara-C. These results suggest that aberrant Hh pathway activation is a feature of some CD34+ myeloid leukemic cells and Hh inhibitors may have a therapeutic role in the treatment of AML.
(キーワード): Antibodies / Antigens, CD34 / Bone Marrow / Drug Resistance, Neoplasm / Gene Expression Regulation, Neoplastic / Hedgehog Proteins / Humans / Leukemia / RNA, Messenger / Receptors, Cell Surface / Signal Transduction / Tumor Cells, Cultured / Veratrum Alkaloids
(出版サイトへのリンク): ● Publication site (DOI): 10.1111/j.1349-7006.2009.01111.x
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19245435; ● Search Scopus @ Elsevier (PMID): 19245435; ● Search Scopus @ Elsevier (DOI): 10.1111/j.1349-7006.2009.01111.x

(DOI: 10.1111/j.1349-7006.2009.01111.x, PubMed: 19245435) Yasushi Sato, Tetsuji Takayama, D Takahari, T Sagawa, T Sato, S Abe, T Kogawa, T Nikaido, K Miyanishi, S Takahashi, J Kato and Y Niitsu :
Successful treatment for gastro-intestinal bleeding of Osler-Weber-Rendu disease by argon plasma coagulation using double-balloon enteroscopy.,
Endoscopy, Vol.40, No.Suppl 2, E228-229, 2008.

(キーワード): Angiodysplasia / Endoscopy, Gastrointestinal / Female / Gastrointestinal Hemorrhage / Humans / Intestinal Diseases / Laser Coagulation / Middle Aged / Telangiectasia, Hereditary Hemorrhagic
(出版サイトへのリンク): ● Publication site (DOI): 10.1055/s-2007-966562
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18991211; ● Summary page in Scopus @ Elsevier: 2-s2.0-63149152843

(DOI: 10.1055/s-2007-966562, PubMed: 18991211, Elsevier: Scopus) Kohichi Takada, Junji Kato, Yutaka Kawano, Sho Takahashi, Tsuyoshi Hayashi, Hirotoshi Ishiwatari, Koji Miyanishi, Rishu Takimoto, Masayoshi Kobune, Tamotsu Sagawa, Tsutomu Sato, 佐藤康史, Toshiharu Yamashita, Hiroshi Natori, Yoshiro Niitsu :
[Effective CDDP arterial infusion with DSM for liver metastasis of malignant melanoma complicating DIC due to intratumoral hemorrhage--a case report].,
癌と化学療法, Vol.35, No.10, 1803-1805, 2008年.

(要約): A 65-year-old male, who had been diagnosed with melanoma of stage IIB and treated by chemotherapy since 2003 at the Dermatology Department, was referred to our department for liver metastasis of melanoma that had become resistant to chemotherapeutic agents. In 2006, he started receiving hepatic arterial infusion of CDDP. He was admitted to the hospital on an emergency basis for general fatigue the next May. Blood tests revealed anemia and thrombocytopenia. Contrast CT showed aggravation of liver metastasis. Contrast ultrasonography revealed nodular contrast enhancement at the margin of the tumor. On the basis of image findings and blood test results, DIC due to intratumoral hemorrhage was diagnosed. CDDP arterial infusion with DSM resulted in improved DIC, and he was able to be discharged. Taken together, attention has to be paid to the potential for emergency complications of DIC due to liver metastasis of melanoma with intratumoral hemorrhage. Moreover, it was shown that arterial infusion with DSM was effective for liver metastasis of melanoma.
(キーワード): Aged / Cerebral Hemorrhage / Cisplatin / Disseminated Intravascular Coagulation / Humans / Infusions, Intra-Arterial / Liver Neoplasms / Male / Melanoma / Microspheres / Starch / Treatment Failure
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18931594; ● Search Scopus @ Elsevier (PMID): 18931594

(PubMed: 18931594) Satoshi Iyama, Takuya Matsunaga, Tsutomu Sato, 佐藤康史, Tamotsu Sagawa, Kazuyuki Murase, Masaya Kida, Masayoshi Kobune, Risyu Takimoto, Junji Kato, Yoshiro Niitsu :
[A case of hepatosplenic gammadelta T-cell lymphoma associated hemophagocytic syndrome].,
癌と化学療法, Vol.35, No.9, 1623-1627, 2008年.

(要約): A 56-year-old woman was admitted to our hospital for examination of high fever, liver dysfunction, pancytopenia, elevated lactate dehydrogenase (LDH) and ferritin, which were not improved by methylprednisolone pulse therapy. Although bone marrow aspiration revealed hypocellularity with no apparent activated macrophages, all other data strongly suggested hemophagocytic syndrome (HPS). She was then treated with chemotherapy consisting of etoposide, prednisolone and cyclosporine, which resulted in transient improvement and allowed her to undergo whole-body fluorine-18fluorodeoxyglucose positron emission tomography (FDG-PET) analysis. FDG uptake was elevated especially in the spleen and liver. A liver biopsy was performed and the examination of the specimen with immunohistochemical staining and PCR analysis revealed monoclonal infiltration of gammadelta T-cell. Despite the repeated chemotherapy, she deteriorated rapidly and succumbed to multi-organ failure. A postmortem examination revealed massive infiltration of activated macrophages with hemophagocytosis in the spleen, liver, bone marrow and perisplenic lymph nodes.
(キーワード): Biopsy / Female / Humans / Liver Neoplasms / Lymphohistiocytosis, Hemophagocytic / Lymphoma, T-Cell / Middle Aged / Positron-Emission Tomography / Receptors, Antigen, T-Cell, gamma-delta / Splenic Neoplasms / Tomography, X-Ray Computed
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18799926; ● Search Scopus @ Elsevier (PMID): 18799926

(PubMed: 18799926) T Sagawa, Y Yamada, M Takahashi, Yasushi Sato, M Kobune, R Takimoto, J Fukaura, S Iyama, T Sato, K Miyanishi, T Matsunaga, Tetsuji Takayama, J Kato, K Sasaki, H Hamada and Y Niitsu :
Treatment of hepatocellular carcinoma by AdAFPep/rep, AdAFPep/p53, and 5-fluorouracil in mice.,
Hepatology, Vol.48, No.3, 828-840, 2008.

(要約): Although conditionally replicable adenovirus (CRAd) has been used in the clinical treatment of hepatocellular carcinoma (HCC), it suffers from the inherent drawback of having relatively low antitumor activity. Here, we have sought to overcome this drawback. First, we combined CRAd (AdAFPep/Rep) driven by alpha-fetoprotein enhancer/promoter (AFPep) with a replication-incompetent adenovirus carrying a p53 transgene that is also driven by AFPep. The synergism of this combination produced a significantly improved tumoricidal effect on the human HCC cell line Hep3B, which has a relatively short doubling time in comparison with other human HCC cell lines, through the transactivation of p53 by early region 1A transcribed by AdAFPep/Rep. This synergistic interaction was augmented by the addition of a subtumoricidal dose (0.5 microg/mL) of 5-fluorouracil (5-FU), which enhanced p53 expression and facilitated the release of virions from tumor cells. When relatively large (10-mm-diameter) Hep3B tumors grown in nude mice were injected with the two viruses in combination, they showed significantly impaired growth in comparison with those treated with each virus separately. The growth suppression effect of the virus combination was enhanced by a low dose (600 microg) of 5-FU. Survival of the tumor-bearing mice treated with these three agents was significantly longer than that of control mice. Moreover, the tumor completely disappeared with the repeated injection of these agents. CONCLUSION: This combination strategy holds promise for the treatment of relatively large and rapidly growing HCCs that may be encountered clinically.
(キーワード): Adenoviridae / Animals / Antimetabolites, Antineoplastic / Carcinoma, Hepatocellular / Cell Line, Tumor / Cells, Cultured / Combined Modality Therapy / Disease Models, Animal / Dose-Response Relationship, Drug / Female / Fluorouracil / Humans / Liver Neoplasms / Mice / Mice, Inbred BALB C / Mice, Nude / Oncolytic Virotherapy / Oncolytic Viruses / Treatment Outcome / Tumor Suppressor Protein p53 / Virus Replication / Xenograft Model Antitumor Assays / alpha-Fetoproteins
(出版サイトへのリンク): ● Publication site (DOI): 10.1002/hep.22420
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18756484; ● Search Scopus @ Elsevier (PMID): 18756484; ● Search Scopus @ Elsevier (DOI): 10.1002/hep.22420

(DOI: 10.1002/hep.22420, PubMed: 18756484) Tsutomu Sato, Takuro Machida, Sho Takahashi, Kazuyuki Murase, Yutaka Kawano, Tsuyoshi Hayashi, Satoshi Iyama, Kohich Takada, Kageaki Kuribayashi, Yasushi Sato, Masayoshi Kobune, Rishu Takimoto, Takuya Matsunaga, Junji Kato and Yoshiro Niitsu :
Apoptosis supercedes necrosis in mitochondrial DNA-depleted Jurkat cells by cleavage of receptor-interacting protein and inhibition of lysosomal cathepsin.,
The Journal of Immunology, Vol.181, No.1, 197-207, 2008.

(要約): In the present study, we used mitochondrial DNA-depleted Jurkat subclones (rho0 cells) to demonstrate that Fas agonistic Ab (CH-11), at the concentrations that evoke apoptotic death of the parental Jurkat cells, induced necrosis mainly through generation of excess reactive oxygen species, lysosomal rupture, and sequential activation of cathepsins B and D, and in minor part through activation of receptor-interacting protein (RIP). In the rho0 cells treated with CH-11, ATP supplementation converted necrosis into apoptosis by the formation of the apoptosome and subsequent activation of procaspase-3. In these ATP-supplemented rho0 cells (ATP-rho0), generation of excess ROS and lysosomal rupture were still seen, yet cathepsins B and D were inactivated and RIP was degraded. The conversion of necrosis to apoptosis, RIP degradation, and cathepsin inactivation in ATP- rho0 cells were blocked by caspase-3 inhibitors. Activities of cathepsins B and D in the lysate of necrotic rho0 cells were inhibited by the addition of apoptotic parental Jurkat cell lysate. Thus, apoptosis may supercede necrosis.
(キーワード): Adenosine Triphosphate / Antibodies / Antigens, CD95 / Apoptosis / Caspase 3 / Caspase 9 / Cathepsin B / Cathepsin D / DNA, Mitochondrial / Humans / Jurkat Cells / Lipid Metabolism / Lysosomes / Necrosis / Oxidation-Reduction / Reactive Oxygen Species / Receptor-Interacting Protein Serine-Threonine Kinases
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18566385; ● Search Scopus @ Elsevier (PMID): 18566385

(PubMed: 18566385) S Takahashi, K Miyanishi, K Takada, Y Kawano, T Sagawa, Yasushi Sato, R Takimoto, Tetsuji Takayama, J Kato, M Omatsu, T Hasegawa, M Kojiro and Y Niitsu :
Case report of a focal nodular hyperplasia-like nodule present in cirrhotic liver.,
Hepatology Research, Vol.38, No.5, 521-528, 2008.

(要約): An 81-year-old female was referred to Sapporo Medical University Hospital because of a nodular lesion 20 mm in diameter found in the liver S8 during follow-up for type C liver cirrhosis. Abdominal ultrasonography showed a capsule-like structure, and contrast computed tomography revealed hypervascularity at the early phase and inner pooling of the contrast medium with ring enhancement at the late phase. Magnetic resonance T2-weighted imaging (T2WI) demonstrated a hyperintensity nodule with further hyperintensity signals in some parts of the nodule, and the signal pattern differed from that of typical fibrosis. SPIO-magnetic resonance imaging showed partial hypointensity signals by T2WI, which indicated the presence of Kupffer cells. Angiography did not show a spoke-wheel pattern. The results by imaging modalities indicated that the nodule was atypical for hepatocellular carcinoma (HCC) and focal nodular hyperplasia (FNH), and liver nodule biopsy was performed for histological diagnosis. Compared with the background liver, the nodule revealed high cellular density, cellular dysplasia at the periphery, a pseudo-crypt structure and irregular hepatic cord arrangement in some parts of the nodule. Among them, there was immature fibrous tissue containing arterioles with muscular hypertrophy. There has been no report of well-differentiated HCC with a central scar, and this case was presumed to be an FNH-like nodule with dysplasia physically associated with cirrhotic tissue.
(出版サイトへのリンク): ● Publication site (DOI): 10.1111/j.1872-034X.2007.00294.x
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18201183; ● Search Scopus @ Elsevier (PMID): 18201183; ● Search Scopus @ Elsevier (DOI): 10.1111/j.1872-034X.2007.00294.x

(DOI: 10.1111/j.1872-034X.2007.00294.x, PubMed: 18201183) A Fujimi, T Matsunaga, M Kobune, Y Kawano, T Nagaya, I Tanaka, S Iyama, T Hayashi, T Sato, K Miyanishi, T Sagawa, Yasushi Sato, R Takimoto, Tetsuji Takayama, J Kato, S Gasa, H Sakai, E Tsuchida, K Ikebuchi, H Hamada and Y Niitsu :
Ex vivo large-scale generation of human red blood cells from cord blood CD34(+) cells by co-culturing with macrophages.,
International Journal of Hematology, Vol.87, No.4, 339-350, 2008.

(要約): We generated red blood cells (RBC) from cord blood (CB) CD34+ cells using a four-phase culture system. We first cultured CB CD34+ cells on telomerase gene-transduced human stromal cells in serum-free medium containing stem cell factor (SCF), Flt-3/Flk-2 ligand, and thrombopoietin to expand CD34+ cells (980-fold) and the total cells (10,400-fold) (first phase). Expanded cells from the first phase were liquid-cultured with SCF, interleukin-3 (IL-3), and erythropoietin (EPO) to expand (113-fold) and differentiate them into erythroblasts (second phase). To obtain macrophages for the next phase, we expanded CD34+ cells from a different donor using the same coculture system. Expanded cells from the first phase were liquid-cultured with granulocyte-macrophage colony stimulating factor, macrophage-colony stimulating factor (M-CSF), IL-3, and SCF to generate monocytes/macrophages (75-fold), which were incubated with type AB serum and M-CSF to fully differentiate them into macrophages. Erythroblasts were then co-cultured with macrophages in the presence of EPO to expand (threefold) and fully differentiate them (61% orthochromatic erythroblasts plus 39% RBC) (third phase). RBC were purified from erythroblasts and debris through a deleukocyting filter to generate 6.0 x 10(12) RBC from 1.0 unit of CB (3.0 transfusable units). Qualitatively, these RBC showed a hemoglobin content, oxygenation of hemoglobin, and in vivo clearance similar to those of adult peripheral RBC. Finally, an almost complete enucleation of orthochromatic erythroblasts (99.4%) was achieved by the cultivation method recently described by Miharada et al. in the absence of macrophages and cytokines (fourth phase). RBC were purified from remnant erythroblasts and debris by passage through a deleukocyting filter to generate 1.76 x 10(13) RBC from 1.0 unit of CB (8.8 transfusable units), the highest yield ever reported. Thus, this method may be useful for generating an alternative RBC supply for transfusions, investigating infectious agents that target erythroid cells, and as a general in vitro hematopoietic model system.
(キーワード): Antigens, CD34 / Cell Differentiation / Cell Separation / Coculture Techniques / Erythroblasts / Erythrocytes / Fetal Blood / Humans / Macrophages / Telomerase
(出版サイトへのリンク): ● Publication site (DOI): 10.1007/s12185-008-0062-y
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18369691; ● Search Scopus @ Elsevier (PMID): 18369691; ● Search Scopus @ Elsevier (DOI): 10.1007/s12185-008-0062-y

(DOI: 10.1007/s12185-008-0062-y, PubMed: 18369691) Yasushi Sato, K Murase, J Kato, M Kobune, T Sato, Y Kawano, R Takimoto, K Takada, K Miyanishi, T Matsunaga, Tetsuji Takayama and Y Niitsu :
Resolution of liver cirrhosis using vitamin A-coupled liposomes to deliver siRNA against a collagen-specific chaperone.,
Nature Biotechnology, Vol.26, No.4, 431-442, 2008.

(要約): There are currently no approved antifibrotic therapies for liver cirrhosis. We used vitamin A-coupled liposomes to deliver small interfering RNA (siRNA) against gp46, the rat homolog of human heat shock protein 47, to hepatic stellate cells. Our approach exploits the key roles of these cells in both fibrogenesis as well as uptake and storage of vitamin A. Five treatments with the siRNA-bearing vitamin A-coupled liposomes almost completely resolved liver fibrosis and prolonged survival in rats with otherwise lethal dimethylnitrosamine-induced liver cirrhosis in a dose- and duration-dependent manner. Rescue was not related to off-target effects or associated with recruitment of innate immunity. Receptor-specific siRNA delivery was similarly effective in suppressing collagen secretion and treating fibrosis induced by CCl(4) or bile duct ligation. The efficacy of the approach using both acute and chronic models of liver fibrosis suggests its therapeutic potential for reversing human liver cirrhosis.
(キーワード): Animals / Collagen / Drug Carriers / Gene Targeting / Gene Therapy / Humans / Liposomes / Liver Cirrhosis / Molecular Chaperones / RNA, Small Interfering / Rats / Treatment Outcome / Vitamin A
(出版サイトへのリンク): ● Publication site (DOI): 10.1038/nbt1396
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18376398; ● Search Scopus @ Elsevier (PMID): 18376398; ● Search Scopus @ Elsevier (DOI): 10.1038/nbt1396

(DOI: 10.1038/nbt1396, PubMed: 18376398) Koji Miyanishi, Hirotoshi Ishiwatari, Tsuyoshi Hayashi, Minoru Takahashi, Yutaka Kawano, Kohichi Takada, Hideyuki Ihara, Toshinori Okuda, Kunihiro Takanashi, Sho Takahashi, Yasushi Sato, Takuya Matsunaga, Hisato Homma, Junji Kato and Yoshiro Niitsu :
A Phase I trial of arterial infusion chemotherapy with gemcitabine and 5-fluorouracil for unresectable advanced pancreatic cancer after vascular supply distribution via superselective embolization.,
Japanese Journal of Clinical Oncology, Vol.38, No.4, 268-274, 2008.

(要約): Arterial infusion chemotherapy using 1000 mg/m(2) gemcitabine on Day 1 and 300 mg/m(2)/day 5-fluorouracil on Days 1-5 every 2 weeks warrants a Phase II study.
(キーワード): Aged / Antimetabolites, Antineoplastic / Antineoplastic Combined Chemotherapy Protocols / Chemoembolization, Therapeutic / Deoxycytidine / Disease-Free Survival / Drug Administration Schedule / Female / Fluorouracil / Humans / Infusions, Intra-Arterial / Male / Maximum Tolerated Dose / Middle Aged / Pancreatic Neoplasms / Patient Selection / Survival Analysis / Treatment Outcome
(出版サイトへのリンク): ● Publication site (DOI): 10.1093/jjco/hyn015
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18375446; ● Search Scopus @ Elsevier (PMID): 18375446; ● Search Scopus @ Elsevier (DOI): 10.1093/jjco/hyn015

(DOI: 10.1093/jjco/hyn015, PubMed: 18375446) 佐藤康史, 高山哲治, Tamotsu Sagawa, Tsutomu Sato, Kumiko Okamoto, Shou Takahashi, Seiichiro Abe, Satoshi Iyama, Kazuyuki Murase, Junji Kato, Yoshiro Niitsu :
[An advanced metastatic breast cancer patient successfully treated with combination therapy including docetaxel, doxorubicin and cyclophosphamide (TAC) as salvage therapy].,
癌と化学療法, Vol.35, No.3, 471-473, 2008年.

(要約): We reported here a case of advanced breast cancer successfully treated with combination therapy including docetaxel, doxorubicin and cyclophosphamide (TAC) as salvage therapy. A 56-year-old male was referred to our hospital for treatment of recurrent metastatic breast cancer. When he was admitted, his general condition was poor due to massive intraperitoneal metastasis. We administered TAC chemotherapy (docetaxel 75 mg/m(2), doxorubicin 50 mg/m(2), and cyclophosphamide 500 mg/m(2), every 3 weeks). During chemotherapy, he showed no major adverse effects except grade 3 neutropenia, which could be easily managed with G-CSF administration. Metastatic lesions almost disappeared after 4 cycles of TAC. TAC therapy was considered to be acceptable as salvage therapy for a metastatic male breast cancer patient.
(キーワード): Antineoplastic Combined Chemotherapy Protocols / Biomarkers, Tumor / Breast Neoplasms / Cyclophosphamide / Doxorubicin / Humans / Male / Middle Aged / Neoplasm Metastasis / Neoplasm Staging / Salvage Therapy / Taxoids / Tomography, X-Ray Computed / Treatment Failure
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18347397; ● Search Scopus @ Elsevier (PMID): 18347397

(PubMed: 18347397) Takehiro Kukitsu, Tetsuji Takayama, Koji Miyanishi, Atsushi Nobuoka, Shinichi Katsuki, Yasushi Sato, Rishu Takimoto, Takuya Matsunaga, Junji Kato, Tomoko Sonoda, Sumio Sakamaki and Yoshiro Niitsu :
Aberrant Crypt Foci as Precursors of the Dysplasia-Carcinoma Sequence in Patients with Ulcerative Colitis.,
Clinical Cancer Research, Vol.14, No.1, 48-54, 2008.

(要約): Long-standing ulcerative colitis (UC) predisposes patients to the development of colorectal cancer, but surveillance of colitis-associated cancer by detecting the precancerous lesion dysplasia is often difficult because of its rare occurrence and normal-looking appearance. In sporadic colorectal cancer, aberrant crypt foci (ACF) have been reported by many investigators to be precursor lesions of the adenoma-carcinoma sequence. In the present study, we analyzed the genetic background of ACF to determine whether they could be precursors for dysplasia, and we examined the usefulness of endoscopic examination of ACF as a surrogate marker for surveillance of colitis-associated cancer. ACF were examined in 28 UC patients (19 patients with UC alone and 9 patients with UC and dysplasia; 2 of those patients with dysplasia also had cancer) using magnifying endoscopy. K-ras, APC, and p53 mutations were analyzed by two-step PCR RFLP, in vitro--synthesized protein assay, and single-strand conformation polymorphism, respectively. Methylation of p16 was analyzed by methylation-specific PCR. ACF that appeared distinct endoscopically and histologically were identified in 27 out of 28 UC patients. They were negative for K-ras, APC, and p53 mutations but were frequently positive for p16 methylation (8 of 11; 73%). In dysplasia, K-ras and APC mutations were negative but p53 mutation (3 of 5; 60%) and p16 methylation (3 of 5; 60%) were positive. There was a significant stepwise increase in the number of ACF from patients with UC alone to patients with dysplasia and to patients with cancer. Univariate and multivariate analyses showed significant correlations between ACF and dysplasia. We have disclosed an ACF-dysplasia-cancer sequence in colitis-associated carcinogenesis similar to the ACF-adenoma-carcinoma sequence in sporadic colon carcinogenesis. This study suggests the use of ACF instead of dysplasia for the surveillance of colitis cancer and warrants further evaluation of ACF as a surveillance marker in large-scale studies.
(キーワード): Adult / Colitis, Ulcerative / Colorectal Neoplasms / Disease Progression / Endoscopy, Gastrointestinal / Female / Genes, APC / Genes, p16 / Genes, p53 / Genes, ras / Humans / Male / Mutation / Polymorphism, Restriction Fragment Length / Polymorphism, Single-Stranded Conformational / Precancerous Conditions / Reverse Transcriptase Polymerase Chain Reaction
(出版サイトへのリンク): ● Publication site (DOI): 10.1158/1078-0432.CCR-07-1835
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18172251; ● Search Scopus @ Elsevier (PMID): 18172251; ● Search Scopus @ Elsevier (DOI): 10.1158/1078-0432.CCR-07-1835

(DOI: 10.1158/1078-0432.CCR-07-1835, PubMed: 18172251) J Kato, K Miyanishi, M Kobune, T Nakamura, K Takada, R Takimoto, Y Kawano, S Takahashi, M Takahashi, Yasushi Sato, Tetsuji Takayama and Y Niitsu :
Long-term phlebotomy with low-iron diet therapy lowers risk of development of hepatocellular carcinoma from chronic hepatitis C.,
Journal of Gastroenterology, Vol.42, No.10, 830-836, 2007.

(要約): We have previously demonstrated that in patients with chronic hepatitis C (CHC), iron depletion improves serum alanine aminotransferase (ALT) levels as well as hepatic oxidative DNA damage. However, it has not been determined whether continuation of iron depletion therapy for CHC favorably influences its progression to hepatocellular carcinoma (HCC). We conducted a cohort study on biopsy-proven CHC patients with moderate or severe liver fibrosis who failed to respond to previous interferon (IFN) therapy or had conditions for which IFN is contradicted. Patients were divided into two groups: subjects in group A (n = 35) underwent weekly phlebotomy (200 g) until they reached a state of mild iron deficiency, followed by monthly maintenance phlebotomy for 44-144 months (median, 107 months), and they were advised to consume a low-iron diet (5-7 mg iron/day); group B (n = 40) comprised CHC patients who declined to receive iron depletion therapy. In group A, during the maintenance phase, serum ALT levels decreased to less than 60 IU/l in all patients and normalized (<40 IU/l) in 24 patients (69%), whereas in group B no spontaneous decrease in serum ALT occurred. Hepatocarcinogenesis rates in groups A and B were 5.7% and 17.5% at the end of the fifth year, and 8.6% and 39% in the tenth year, respectively. Multivariate analysis revealed that iron depletion therapy significantly lowered the risk of HCC (odds ratio, 0.57) compared with that of untreated patients (P = 0.0337). Long-term iron depletion for CHC patients is a promising modality for lowering the risk of progression to HCC.
(キーワード): Adult / Aged / Alanine Transaminase / Carcinoma, Hepatocellular / Cohort Studies / Diet / Female / Follow-Up Studies / Hepatitis C, Chronic / Humans / Iron / Iron, Dietary / Liver Cirrhosis / Male / Middle Aged / Multivariate Analysis / Phlebotomy / Risk Factors
(出版サイトへのリンク): ● Publication site (DOI): 10.1007/s00535-007-2095-z
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 17940836; ● Search Scopus @ Elsevier (PMID): 17940836; ● Search Scopus @ Elsevier (DOI): 10.1007/s00535-007-2095-z

(DOI: 10.1007/s00535-007-2095-z, PubMed: 17940836) Tetsuji Takayama, Yasushi Sato, T Sagawa, T Okamoto, H Nagashima, Y Takahashi, H Ohnuma, G Kuroiwa, K Miyanishi, R Takimoto, T Matsunaga, J Kato, K Yamaguchi, K Hirata and Y Niitsu :
Phase I study of S-1, docetaxel and cisplatin combination chemotherapy in patients with unresectable metastatic gastric cancer.,
British Journal of Cancer, Vol.97, No.7, 851-856, 2007.

(要約): The aim of this dose escalation study was to determine the maximum-tolerated dose (MTD), dose-limiting toxicities (DLTs) and preliminary efficacy of docetaxel, S-1 and cisplatin combination chemotherapy in patients with unresectable metastatic gastric cancer. Seventeen patients received oral S-1 (40 mg m(-2) bid) on days 1-14, intravenous cisplatin (60 mg m(-2)) and docetaxel (60, 70 or 80 mg m(-2) depending on DLT) on day 8 every 3 weeks. The MTD of this combination was presumed to be docetaxel 70 mg m(-2). At this dose level, 40% of the patients (two of five) developed grade 4 neutropenia and 20% (one of five) exhibited grade 3 nausea during the first course. Therefore, the recommended dose of docetaxel was defined as 60 mg m(-2). The DLT was neutropenia. The response rate (RR) was 88.2% (15 of 17), consisting of one complete response and 14 partial responses. There were two stable diseases but no progressive disease. Of these 15 responders, four (23.5%) with high VEGF expression showed rapid tumour regression and achieved downstaging, leading to subsequent curative gastrectomy. Three of these have been disease free for about 3 years, suggesting a complete cure. In conclusion, this regimen was tolerable and showed a quite high RR, with an appreciable downstaging rate in metastatic gastric cancer.
(キーワード): Aged / Antineoplastic Combined Chemotherapy Protocols / Cisplatin / Drug Combinations / Female / Humans / Immunoenzyme Techniques / Intestinal Neoplasms / Male / Maximum Tolerated Dose / Middle Aged / Oxonic Acid / Stomach Neoplasms / Taxoids / Tegafur / Vascular Endothelial Growth Factor A
(出版サイトへのリンク): ● Publication site (DOI): 10.1038/sj.bjc.6603957
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 17848958; ● Search Scopus @ Elsevier (PMID): 17848958; ● Search Scopus @ Elsevier (DOI): 10.1038/sj.bjc.6603957

(DOI: 10.1038/sj.bjc.6603957, PubMed: 17848958) Kaoru Ono, Satoshi Iyama, Takuya Matsunaga, Tsutomu Sato, 佐藤康史, Toshinori Okuda, Kohichi Takada, Yutaka Kawano, Tsuyoshi Hayashi, Koji Miyanishi, Tamotsu Sagawa, Masayoshi Kobune, Rishu Takimoto, Junji Kato, Yoshiro Niitsu :
[Reactivation of hepatitis B virus due to rituximab plus CHOP after preemptive lamivudine administration in a patient with diffuse large B-cell lymphoma].,
癌と化学療法, Vol.34, No.9, 1509-1512, 2007年.

(要約): A 59-year-old woman received eight cycles of R-CHOP for diffuse large B-cell lymphoma from July, 2004. Pretreatment HBV serological tests were positive, however, the transaminases were within normal limits, and she remained asymptomatic. Lamivudine (LAM) was administered orally from the start of R-CHOP. HBV-DNA levels gradually decreased and were not detected until December, 2004. LAM was administered until 3 months after the end of chemotherapy, with the entire treatment lasting less than 1 year. Two months after the cessation of treatment, she was re-admitted for general malaise. A liver function test revealed severe abnormalities, and HBVDNA levels were increased. Clinically, she was experiencing acute hepatitis due to HBV reactivation. She was then treated with LAM and interferon-beta immediately. Her HBV-DNA levels soon decreased, and liver function improved.
(キーワード): Anti-HIV Agents / Antibodies, Monoclonal / Antibodies, Monoclonal, Murine-Derived / Antineoplastic Combined Chemotherapy Protocols / Cyclophosphamide / DNA, Viral / Doxorubicin / Female / Hepatitis B / Hepatitis B virus / Humans / Interferon-beta / Lamivudine / Lymphoma, B-Cell / Middle Aged / Prednisone / Rituximab / Vincristine / Virus Activation
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 17876158; ● Search Scopus @ Elsevier (PMID): 17876158

(PubMed: 17876158) Tamotsu Sagawa, 佐藤康史, 高山哲治, Masahiro Hirakawa, Seiichiro Abe, Satoshi Iyama, Koji Miyanishi, Yutaka Kawano, Kohichi Takada, Tokiko Nakamura, Junji Kato, Yoshiro Niitsu :
[A case of resection of synchronous multiple liver metastases from colorectal cancer after hepatic infusion chemotherapy and systemic chemotherapy].,
癌と化学療法, Vol.34, No.9, 1481-1484, 2007年.

(要約): A 70-year-old man was admitted for tranverse colon cancer with multiple liver metastases. Hepatic arterial infusion chemotherapy and systemic chemotherapy (FOLFOX 4) were conducted postoperatively. Thirteen months after the first surgery, liver metastases became resectable and hepatectomy was performed. Though multiple liver metastases were unresectable at the time of the first examination, hepatectomy was possible followed by hepatic arterial infusion chemotherapy and systemic chemotherapy.
(キーワード): Adenocarcinoma / Aged / Antineoplastic Combined Chemotherapy Protocols / Colorectal Neoplasms / Combined Modality Therapy / Fluorouracil / Hepatectomy / Humans / Infusions, Intra-Arterial / Infusions, Intravenous / Leucovorin / Liver Neoplasms / Male / Organoplatinum Compounds
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 17876151; ● Search Scopus @ Elsevier (PMID): 17876151

(PubMed: 17876151) Tamotsu Sagawa, 佐藤康史, 高山哲治, Hiroyuki Kuroda, Masahiro Hirakawa, Seiichiro Abe, Satoshi Iyama, Sumio Sakamaki, Junji Kato, Yoshiro Niitsu :
[Fifth-line chemotherapy for metastatic gastric cancer--a case responding to modified FOLFOX 6].,
癌と化学療法, Vol.34, No.9, 1467-1471, 2007年.

(要約): According to the National Comprehensive Cancer Network (NCCN) clinical practice guideline for gastric cancer (2006, the first edition), 5-FU/Leucovorin (LV), 5-FU-based, cisplatin (CDDP)-based, oxaliplatin (L-OHP)-based, taxane-based, and irinotecan (CPT-11)-based, ECF are recommended. We used modified FOLFOX 6 (mFOLFOX 6) for pretreatment, that is oxaliplatin-based chemotherapy, for a patient who had received 5-FU-based, CDDPbased, taxane-based, and CPT-11-based treatment for an unresectable gastric cancer case responding to mFOLFOX 6. A 73-year-old male admitted to our hospital for treatment of advanced gastric cancer was diagnosed to be inoperable. A combination chemotherapy docetaxel and CDDP and S-1 as first-line treatment, CPT-11 and CDDP as second-line treatment, weekly paclitaxel treatment as third-line treatment, and MTX and 5-FU as fourth-line treatment were performed. He had progressed after 5-FU-based, CDDP-based, taxane-based, and CPT-11-based chemotherapy. There are no effective approved drugs for gastric cancer in Japan. Oxaliplatin was reportedly effective for metastatic gastric cancer, but it is still non-approved in Japan. After receiving an explanation of oxaliplatin-based therapy, he gave informed consent. Oxaliplatin-based therapy for this patient was then evaluated and approved under an institutional review board of Higashi Sapporo Hospital. mFOLFOX 6 used for the oxaliplatin-based therapy. After 2 courses of mFOLFOX 6, he showed a partial response. Oxaliplatin-based treatment was thought to be promising for previously CDDP-treated patients with unresectable gastric cancers.
(キーワード): Aged / Antineoplastic Combined Chemotherapy Protocols / Fluorouracil / Humans / Leucovorin / Male / Organoplatinum Compounds / Stomach Neoplasms / Treatment Outcome
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 17876148; ● Search Scopus @ Elsevier (PMID): 17876148

(PubMed: 17876148) 佐藤康史, 高山哲治, Tomomi Nikaido, Yuko Wada, Tamotsu Sagawa, Seiichiro Abe, Tsutomu Sato, Satoshi Iyama, Kazuyuki Murase, Hironobu Araki, Yasuhiro Sato, Junji Kato, Yoshiro Niitsu, Hideki Chiba :
Report of an autopsy case of colon cancer with amyotrophic lateral sclerosis.,
日本消化器病学会雑誌, Vol.104, No.9, 1365-1370, 2007年.

(要約): Amyotrophic lateral sclerosis (ALS) is a degenerative disease involving both upper and lower motor neurons and the pathogenesis of this disorder is still unknown. To date, few reports have suggested that motor neuron diseases may have a paraneoplastic origin. However, it is still under discussion whether ALS occurring in cancer patients is paraneoplastic. A 60-year-old man with rectal cancer (Stage IV) having multiple lung, liver and para-aortic lymph node metastases underwent anterior resection of the rectum as palliative surgery. He was referred to our hospital for adjuvant chemotherapy. Lung and lymph node metastases decreased after 2 courses of chemotherapy using CPT-11 and 5-FU/LV but liver metastases were enlarged, following up increase in CEA. Thereafter, he suffered from muscle weakness in hands, arms, and legs and results of neurophysiologic studies were compatible with primary lateral sclerosis (ALS). For second line chemotherapy, he was treated with low-dose CDDP/5-FU over 6 courses. As a result, the size the of metastatic lesions markedly reduced and CEA was decreased to the normal level. Although significant tumor reduction was observed, his neurological symptoms rapidly progressed. He died of aspiration pneumonia 8 months after onset of the disease. Autopsy revealed that his neuropathological findings were compatible with ALS, and it was thought to be the primary cause of death in the because of absence of cancer progression. In this case the neurological syndrome was not affected by cancer therapy. Thus our case does not support the hypothesis that ALS in associated with cancer and the relationship between both disorders remains uncertain.
(キーワード): Adenocarcinoma / Amyotrophic Lateral Sclerosis / Antineoplastic Combined Chemotherapy Protocols / Camptothecin / Cisplatin / Colonic Neoplasms / Drug Administration Schedule / Fluorouracil / Humans / Leucovorin / Liver Neoplasms / Lung Neoplasms / Male / Middle Aged
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 17827908; ● Search Scopus @ Elsevier (PMID): 17827908

(PubMed: 17827908) Tsutomu Sato, Satoshi Iyama, Naoko Araki, Kazuyuki Murase, 佐藤康史, Masayoshi Kobune, Rishu Takimoto, Takuya Matsunaga, Junji Kato, Hiroyuki Kuroda, Yoshiro Niitsu :
[Factor XI deficiency caused by a mutation of Gly400Val].,
臨床血液, Vol.48, No.2, 148-150, 2007年.

(要約): The patient described herein is a 69-year-old Japanese woman with a history of excessive bleeding after left heminephrectomy for a malignant renal tumor at 31 years of age. Her parents, who do not have abnormal bleeding, are first cousins. Her factor XI activity was less than 1% of normal with an prolonged activated partial thromboplastin time (APTT) of 74.3 seconds. Analysis of the patient's factor XI genes revealed homozygosity for a valine substituting for the wild-type glycine at amino acid 400 (Gly400Val). The patient has two children, neither of whom has abnormal bleeding and whose factor XI activities are 62% and 57% of normal, with APTT levels within normal limits in both cases. We herein report on a Japanese family with factor XI deficiency caused by Gly400Val mutation.
(キーワード): Aged / Amino Acid Substitution / Codon / DNA / Exons / Factor XI / Factor XI Deficiency / Female / Glycine / Homozygote / Humans / Mutation, Missense / Valine
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 17370644; ● Search Scopus @ Elsevier (PMID): 17370644

(PubMed: 17370644) Tsutomu Sato, Rishu Takimoto, Satoshi Iyama, Kaoru Ono, Shingo Tanaka, Naoko Araki, Kiwami Nishiie, Kazuyuki Murase, 佐藤康史, Masayoshi Kobune, Takuya Matsunaga, Junji Kato, Yoshiro Niitsu :
[Gastric relapse of stage I ocular adnexal mucosa-associated lymphoid tissue lymphoma].,
臨床血液, Vol.48, No.1, 56-60, 2007年.

(要約): A 57-year-old male with right ocular adnexal mucosa-associated lymphoid tissue lymphoma (MALT lymphoma) was successfully treated with local radiation therapy. The gastroendoscopic examination revealed a slight inflammatory change of the gastric mucosa, and the urease test was positive. Eradication therapy against Helicobacter pylori was successfully done, however, the patient developed gastric MALT lymphoma two years after the initial treatment. Southern blot analysis of the immunoglobulin heavy chain gene rearrangement revealed that the lymphoma cells from the ocular adnexal and gastric MALT lymphomas were identical, indicating that the gastric MALT lymphoma was not the primary but the metastatic region from the ocular adnexal MALT lymphoma. Further, immunohistochemical staining demonstrated the expression of integrin alpha4beta 7 on ocular adnexal MALT lymphoma cells, which is essential for the adhesion of lymphocytes to gastrointestinal mucosa. These results indicate that ocular adnexal MALT lymphoma cells can metastasize to the stomach, depending on the adhesional function of integrin alpha4 beta7.
(キーワード): Eye Neoplasms / Gastroscopy / Helicobacter Infections / Helicobacter pylori / Humans / Integrins / Lacrimal Apparatus / Lymphoma, B-Cell, Marginal Zone / Male / Middle Aged / Oncogene Proteins, Fusion / Stomach Neoplasms
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 17313077; ● Search Scopus @ Elsevier (PMID): 17313077

(PubMed: 17313077) Tamotsu Sagawa, 佐藤康史, Seiichiro Abe, Toshinori Okuda, Naoko Araki, Daisuke Takahari, Tetsuro Okamoto, 高山哲治, Junji Kato, Yoshiro Niitsu :
[Anaphylactic reaction to oxaliplatin--a case of colon cancer].,
癌と化学療法, Vol.33, No.13, 2093-2096, 2006年.

(要約): Oxaliplatin (L-OHP) is a new third-generation platinum which is efficacious in treating advanced unresectable recurrent colorectal cancer as a first-line regimen. The marketing authorization was given in Japan in March, 2005. Its increased use has resulted in rare serious adverse effects, including anaphylactic shock. We experienced a case that developed anaphylactic shock by L-OHP. We report a 69-year-old man who was treated for recurrent colorectal cancer who underwent systemic chemotherapy with FOLFOX 4. After eight cycles he developed severe L-OHP associated neuropathy and lung metastases was a progressive tendency. The FOLFOX 4 regimen was discontinued and another modality, FOLFIRI regimen, was used. After eight cycles of FOLFIRI regimen, lung and liver metastases showed progressive disease for response assessment by RECIST criteria. Although a patient was stopped L-OHP for neurotoxicity, neuropathy was disappeared after 4 months interval. Therefore, we reintroduced L-OHP, FOLFOX 4 regimen. Anaphylactic shock occurred in the second cycle of reintroduction of the FOLFOX 4 regimen (total 10 cycles), 30 minutes after infusion of L-OHP. L-OHP infusion was immediately withdrawn and he was treated with intravenous hydroxyzine hydrochloride and methylprednisolone. The anaphylaxis symptoms resolved in 30 minutes. Chemotherapy based on L-OHP for unresectable recurrence colorectal cancer causes anaphylactic shock as a rare severe complication. The prediction factor is not proved. We should take steps for early detection of anaphylactic reaction and perform the appropriate treatment.
(キーワード): Adenocarcinoma / Aged / Anaphylaxis / Antineoplastic Agents / Antineoplastic Combined Chemotherapy Protocols / Colonic Neoplasms / Drug Administration Schedule / Fluorouracil / Humans / Leucovorin / Male / Organoplatinum Compounds
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 17197761; ● Search Scopus @ Elsevier (PMID): 17197761

(PubMed: 17197761) Takuya Matsunaga, Tsutomu Sato, Satoshi Iyama, Shingo Tanaka, Kazuyuki Murase, 佐藤康史, Masayoshi Kobune, Rishu Takimoto, Junji Kato, Hiroyuki Kuroda, Yoshiro Niitsu :
[Peripheral T-cell lymphoma presenting with eosinophilia due to interleukin-5 produced by lymphoma cells].,
臨床血液, Vol.47, No.11, 1457-1462, 2006年.

(要約): A 72-year-old male was admitted to our hospital to determine the cause of neck lymphadenopathies. He was diagnosed pathologically by a lymph node biopsy as having peripheral T-cell lymphoma (PTCL). He also had developed eosinophilia and his serum concentration of Interleukin-5 (IL-5) was extremely high. Immunostaining of a resected lymph node revealed that there were lymphoma cells which were stained with anti-IL-5 antibody. After 2 courses of CHOP therapy, the lymphadenopathies and eosinophilia disappeared and the concentration of serum IL-5 was normalized. It was suggested that IL-5 produced by lymphoma cells had induced his eosinophilia.
(キーワード): Aged / Eosinophilia / Humans / Interleukin-5 / Lymphoma, T-Cell, Peripheral / Male
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 17176889; ● Search Scopus @ Elsevier (PMID): 17176889

(PubMed: 17176889) Satoshi Iyama, Yasuo Takahashi, Naoaki Shintani, Koshi Fujikawa, Syunichi Ohkubo, 佐藤康史, Tsutomu Sato, Yasuhiro Sato, Keisuke Ohnuma, Yoshiro Niitsu :
[A case of recurrent biliary cystadenocarcinoma successfully treated with 5FU/CDDP systemic chemotherapy].,
日本消化器病学会雑誌, Vol.103, No.10, 1163-1168, 2006年.

(要約): We report a case of biliary cystadenocarcinoma which recurred 41 months postoperatively. A 60-year-old woman was admitted for further examination of multiple metastatic tumors and a large amount of ascites. Systemic administration of 5FU and CDDP caused her CEA level to decrease gradually and abdominal computed tomography revealed considerable reduction of the metastatic tumors and ascites. Since her general condition had improved, chemotherapy was continued in the outpatient clinic.
(キーワード): Antineoplastic Combined Chemotherapy Protocols / Biliary Tract Neoplasms / Cisplatin / Cystadenocarcinoma / Female / Fluorouracil / Humans / Middle Aged / Neoplasm Recurrence, Local
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 17023760; ● Search Scopus @ Elsevier (PMID): 17023760

(PubMed: 17023760) Takuya Matsunaga, Ikuta Tanaka, Masayoshi Kobune, Yutaka Kawano, Maki Tanaka, Kageaki Kuribayashi, Satoshi Iyama, Tsutomu Sato, Yasushi Sato, Rishu Takimoto, Tetsuji Takayama, Junji Kato, Takafumi Ninomiya, Hirofumi Hamada and Yoshiro Niitsu :
Ex vivo large scale generation of human platelets from cord blood CD34+ cells.,
Stem Cells, Vol.24, No.12, 2877-2887, 2006.

(要約): In the present investigation, we generated platelets (PLTs) from cord blood (CB) CD34(+) cells using a three-phase culture system. We first cultured 500 CB CD34(+) cells on telomerase gene-transduced human stromal cells (hTERT stroma) in serum-free medium supplemented with stem cell factor (SCF), Flt-3/Flk-2 ligand (FL), and thrombopoietin (TPO) for 14 days. We then transferred the cells to hTERT stroma and cultured for another 14 days with fresh medium containing interleukin-11 (IL-11) in addition to the original cytokine cocktail. Subsequently, we cultured the cells in a liquid culture medium containing SCF, FL, TPO, and IL-11 for another 5 days to recover PLT fractions from the supernatant, which were then gel-filtered to purify the PLTs. The calculated yield of PLTs from 1.0 unit of CB (5 x 10(6) CD34(+) cells) was 1.26 x 10(11) - 1.68 x 10(11) PLTs. These numbers of PLTs are equivalent to 2.5-3.4 units of random donor-derived PLTs or 2/5-6/10 of single-apheresis PLTs. The CB-derived PLTs exhibited features quite similar to those from peripheral blood in morphology, as revealed by electron micrographs, and in function, as revealed by fibrinogen/ADP aggregation, with the appearance of P-selectin and activated glycoprotein IIb-IIIa antigens. Thus, this culture system may be applicable for large-scale generation of PLTs for future clinical use.
(キーワード): Antigens, CD34 / Blood Platelets / Cell Culture Techniques / 細胞分化 (cell differentiation) / Cell Lineage / 細胞質分裂 (cytokinesis) / Endothelial Cells / Fetal Blood / HLA Antigens / Humans / Megakaryocytes / Platelet Membrane Glycoprotein IIb / Ploidies / Stem Cells / Stromal Cells / Telomerase
(出版サイトへのリンク): ● Publication site (DOI): 10.1634/stemcells.2006-0309
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16960134; ● Search Scopus @ Elsevier (PMID): 16960134; ● Search Scopus @ Elsevier (DOI): 10.1634/stemcells.2006-0309

(DOI: 10.1634/stemcells.2006-0309, PubMed: 16960134) Tsutomu Sato, Takuya Matsunaga, Satoshi Iyama, Toshiro Sakai, Kazuyuki Murase, Yasushi Sato, Masayoshi Kobune, Rishu Takimoto, Junji Kato and Yoshiro Niitsu :
[Enteropathy-type T-cell lymphoma with CD8 and CD56 expression].,
The Japanese Journal of Clinical Hematology, Vol.47, No.7, 645-649, 2006.

(要約): A 54-year-old male presented at a previous hospital with abdominal pain, where the patient was diagnosed as having abdominal and retroperitoneal lymphadenopathies by CT scan, then, he was referred to our hospital for further examination. Upper gastrointestinal endoscopy showed a tumor formation in the second portion of the duodenum, and there were medium sized atypical lymphocytes in biopsy specimens of the tumor. Since the atypical lymphocytes in the biopsy specimens were positive for CD3, CD8, CD56 and CD103 by immunostain, and had a rearrangement of the T-cell receptor 7-chain, the patient was diagnosed as having enteropathy-type T-cell lymphoma (ETL). Although ETL usually occurs as a complication of celiac disease, malabsorption and anti-gliadin antibodies, which are normally present in celiac disease, were not observed in this patient.
(キーワード): Antigens, CD3 / Antigens, CD56 / Antigens, CD8 / Duodenal Neoplasms / Endoscopy, Gastrointestinal / Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor / Humans / Lymphoma, T-Cell / Male / Middle Aged
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16910575; ● Search Scopus @ Elsevier (PMID): 16910575

(PubMed: 16910575) T Oku, S Iyama, T Sato, Yasushi Sato, M Tanaka, T Sagawa, K Kuribayashi, T Sumiyosi, K Murase, T Machida, T Okamoto, T Matsunaga, Tetsuji Takayama, M Takahashi, J Kato, H Hamada and Y Niitsu :
Amelioration of murine dextran sulfate sodium-induced colitis by ex vivo extracellular superoxide dismutase gene transfer.,
Inflammatory Bowel Diseases, Vol.12, No.7, 630-640, 2006.

(要約): Although the etiology of inflammatory bowel disease has not been fully clarified, reactive oxygen species is speculated to be involved. Extracellular superoxide dismutase (EC-SOD), an isozyme of SODs, is known to function mainly in body fluids. We investigated the efficacy of an ex vivo EC-SOD gene transfer into dextran sulfate sodium (DSS)-induced colitis mice. Experimental colitis was induced by providing Balb/c mice with DSS in sterile distilled water provided as desired. The syngenic fibroblasts were obtained from Balb/c mice embryos and retrovirally transduced with the hEC-SOD gene. These engineered cells were confirmed to secrete EC-SOD in culture medium by enzyme-linked immunosorbent assay and were inoculated subcutaneously in the backs of DSS-treated mice. Mucosal injury of the colon was evaluated by the disease activity index (DAI: body weight, rectal bleeding, and stool consistency), grading of histologic disease severity, and levels of cytokine (tumor necrosis factor-alpha, interleukin-1beta) production. 8-Hydroxydeoxyguanosine (8-OHdG) levels in the mucosal tissue were assessed by immunohistochemical staining. Malondialdehyde (MDA) was measured using a colorimetric assay. A significant improvement was observed in DAI score and histologic severity as well as in mucosal tissue levels of inflammatory cytokines, 8-OHdG, and MDA of mice treated with the EC-SOD gene as compared with those without gene therapy, not only in a mild colitis model but also in a severe colitis model. Survival of treated mice in these models was significantly prolonged. Ex vivo transfer of the EC-SOD gene was feasible for treatment of DSS-induced colitis.
(キーワード): Animals / Anticoagulants / Colitis / Culture Media / Cytokines / Dextran Sulfate / Female / Fibroblasts / Gene Therapy / Gene Transfer Techniques / Immunohistochemistry / Inflammation / Malondialdehyde / Mice / Mice, Inbred BALB C / Reactive Oxygen Species / Superoxide Dismutase
(出版サイトへのリンク): ● Publication site (DOI): 10.1097/01.MIB.0000225335.68614.73
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16804401; ● Search Scopus @ Elsevier (PMID): 16804401; ● Search Scopus @ Elsevier (DOI): 10.1097/01.MIB.0000225335.68614.73

(DOI: 10.1097/01.MIB.0000225335.68614.73, PubMed: 16804401) Yasushi Sato, J Kato, R Takimoto, K Takada, Y Kawano, K Miyanishi, M Kobune, Y Sato, Tetsuji Takayama, T Matsunaga and Y Niitsu :
Hepatitis C virus core protein promotes proliferation of human hepatoma cells through enhancement of transforming growth factor-{alpha} expression via activation of NF-{kappa}B.,
Gut, Vol.55, No.12, 1801-1808, 2006.

(要約): Hepatitis C virus (HCV) infection is a major cause of human hepatocellular carcinoma (HCC). The precise mechanism of hepatocarcinogenesis in humans by HCV is currently unclear. It was recently shown, however, that transgenic mice with the HCV core gene often develop HCC, suggesting tumorigenic activity of the HCV core protein. Further, the HCV core protein expressed in HepG2 cells transfected with the core gene was shown to stimulate proliferation of transfectants through activation of nuclear factor-kappaB (NF-kappaB). The downstream target molecule(s) of NF-kappaB activated by the HCV core protein to evoke cell proliferation is not yet identified. Transforming growth factor (TGF) alpha, which is often overexpressed in various tumour tissues such as HCC, has been shown to stimulate hepatocyte proliferation through activation of the mitogen-activated protein kinase or extracellular signal-related protein kinase (MAPK/ERK) cascade. To explore the possibility that TGFalpha might be a target molecule for NF-kappaB activated by the HCV core, and that TGFalpha participates in the growth promotion of the core transfectants in an autocrine manner, activating the MAPK/ERK pathway. A HCV core expression vector was transfected into human hepatoma Huh-7, HepG2 and Hep3B cells. NF-kappaB activity was examined by an electrophoretic mobility shift assay. TGFalpha transcription was assessed by a luciferase reporter assay. TGFalpha protein was determined by immunoblot and ELISA. MAPK/ERK activity was examined by an in vitro kinase assay. Cell proliferation was assessed by a water-soluble tetrazolium salt-1 assay. In the HCV core transfectants, NF-kappaB bound to the kappaB site in the TGFalpha proximal promoter region, resulting in an increase in TGFalpha transcription. Immunoblot as well as ELISA showed increased TGFalpha expression in the HCV core transfectants. SN50, a specific inhibitory peptide for NF-kappaB, cancelled HCV core-induced TGFalpha expression. HCV core protein increased cell proliferation as well as ERK activity of the HCV core transfectants as compared with the mock transfectants. The growth-promoting activity and activation of ERK by the HCV core protein were negated by treatment with anti-TGFalpha antibodies. These results suggest that the HCV core protein promotes proliferation of human hepatoma cells by activation of the MAPK/ERK pathway through up regulation of TGFalpha transcription via activation of NF-kappaB. Our finding provides a new insight into the mechanism of hepatocarcinogenesis by HCV infection.
(キーワード): Carcinoma, Hepatocellular / Cell Division / Cell Line, Tumor / Enzyme Activation / Hepacivirus / Humans / Liver Neoplasms / Mitogen-Activated Protein Kinases / NF-kappa B / Neoplasm Proteins / Peptides / Transcription, Genetic / Transfection / Transforming Growth Factor alpha / Viral Core Proteins
(出版サイトへのリンク): ● Publication site (DOI): 10.1136/gut.2005.070417
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16581947; ● Search Scopus @ Elsevier (PMID): 16581947; ● Search Scopus @ Elsevier (DOI): 10.1136/gut.2005.070417

(DOI: 10.1136/gut.2005.070417, PubMed: 16581947) Tetsuji Takayama, K Miyanishi, T Hayashi, Yasushi Sato and Y Niitsu :
Colorectal Cancer: genetics of development and metastasis.,
Journal of Gastroenterology, Vol.41, No.3, 185-192, 2006.

(要約): It has been well documented that there are two major pathways in colorectal carcinogenesis. One is the chromosomal instability pathway (adenoma-carcinoma sequence), which is characterized by allelic losses on chromosome 5q (APC), 17p (p53), and 18q (DCC/SMAD4), and the other is a pathway that involves microsatellite instability. Recent progress in molecular biology, however, has shown that colorectal carcinogenesis is not necessarily clearly divided into these two pathways, but is in fact more complicated. Other routes, including the transforming growth factor-beta/SMAD pathway, the serrated pathway, and the epigenetic pathway, have been reported. Cross talk among these pathways has also been reported. In the invasion and metastasis steps of colorectal cancers, many more genes have now been identified as being involved in proteolysis, adhesion, angiogenesis, and cell growth. Recently accumulated evidence indicates that colorectal cancer is a genetically heterogeneous and complicated disease.
(キーワード): Adenocarcinoma / Carcinoma / Cell Transformation, Neoplastic / Chromosomal Instability / Colorectal Neoplasms / Epigenesis, Genetic / Gene Expression Regulation, Neoplastic / Genes, Tumor Suppressor / Genes, ras / Genetic Predisposition to Disease / Humans / Microsatellite Instability / Signal Transduction / Smad4 Protein / Transforming Growth Factor beta / Tumor Suppressor Proteins
(出版サイトへのリンク): ● Publication site (DOI): 10.1007/s00535-006-1801-6
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16699851; ● Search Scopus @ Elsevier (PMID): 16699851; ● Search Scopus @ Elsevier (DOI): 10.1007/s00535-006-1801-6

(DOI: 10.1007/s00535-006-1801-6, PubMed: 16699851) Yasushi Sato, Tetsuji Takayama, T Sagawa, T Okamoto, K Miyanishi, T Sato, H Araki, S Iyama, S Abe, K Murase, R Takimoto, H Nagakura, M Hareyama and Y Niitsu :
A phase I/II study of nedaplatin and 5-fluorouracil with concurrent radiotherapy in patients with esophageal cancer.,
Cancer Chemotherapy and Pharmacology, Vol.58, No.5, 570-576, 2006.

(要約): To determine the recommended dose (RD) of cis-diammine-glycolatoplatinum (nedaplatin) when given concurrently with 5-FU and high dose radiation therapy in the treatment of esophageal cancer. The purpose of the phase II trial is to determine efficacy and further define the side effect profile. Twenty-six patients with clinical stage I to IVA squamous cell carcinoma of the esophagus were enrolled in a non-surgical treatment comprised of a fixed dose of fluorouracil (400 mg/m2 administered as continuous intravenous infusion on days 1-5 and days 8-12) plus escalating doses of nedaplatin (40 mg/m2 in level 1, 50 mg/m2 in level 2, or 60 mg/m2 in level 3 on days 1 and 8), repeated twice every 3 weeks with concurrent radiotherapy (60 Gy). Between July 1998 and February 2004, a total of 26 patients entered this trial, all of whom were considered evaluable for toxicity assessment. In phase I of the study, 12 patients were treated in sequential cohorts of three to six patients per dose level. The maximum tolerated dose was reached at level 3 with two grade 4 neutropenia and one grade 4 thrombocytopenia. Thus, the recommended dosing schedule is level 2. Of the 20 patients treated at the RD level 2, including 6 patients of the RD phase I portion, 8 out of 20 patients (40%) had grade 3-4 neutropenia, 5 patients (25.0%) had grade 3-4 thrombocytopenia, 4 patients (20.0%) had grade 3 anemia and 4 patients (20.0%) had grade 3-4 esophagitis. Other toxicities were relatively mild and usually of grade 2 or less. Objective responses were noted in the 26 patients (overall response rate, 88.5%) including 11 (42.3%) complete remissions. The 1- and 3-year survival rates were 65.1 and 37.2%, respectively, with a median survival time of 21.2 months. The combination of nedaplatin and 5-FU with radiation is a feasible regimen that shows promising antitumor activity with an acceptable safety profile in patients with esophageal cancer.
(キーワード): Aged / Anemia / Antineoplastic Combined Chemotherapy Protocols / Dose-Response Relationship, Drug / Esophageal Neoplasms / Esophagitis / Female / Fluorouracil / Humans / Infusions, Intravenous / Male / Middle Aged / Nausea / Neutropenia / Organoplatinum Compounds / Radiotherapy, Adjuvant / Remission Induction / Severity of Illness Index / Survival Rate / Thrombocytopenia / Treatment Outcome
(出版サイトへのリンク): ● Publication site (DOI): 10.1007/s00280-006-0193-x
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16463059; ● Search Scopus @ Elsevier (PMID): 16463059; ● Search Scopus @ Elsevier (DOI): 10.1007/s00280-006-0193-x

(DOI: 10.1007/s00280-006-0193-x, PubMed: 16463059) Yasuhiro Sato, Yasuo Takahashi, Kiwami Nishiie, Shuniti Okubo, Koji Fujikaw, Naoaki Shintani, Koichi Takada, 佐藤康史, Rishu Takimoto, Junji Kato, Yoshiro Niitsu :
[A case of granulocyte-colony stimulating factor producing small cell carcinoma of esophagus].,
日本消化器病学会雑誌, Vol.102, No.7, 888-893, 2005年.

(キーワード): Aged / Antineoplastic Combined Chemotherapy Protocols / Carcinoma, Small Cell / Cisplatin / Drug Administration Schedule / Esophageal Neoplasms / Etoposide / Granulocyte Colony-Stimulating Factor / Humans / Male / Remission Induction
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16038435; ● Search Scopus @ Elsevier (PMID): 16038435

(PubMed: 16038435) R Takimoto, J Kato, T Terui, K Takada, G Kuroiwa, J Wu, H Ohnuma, D Takahari, M Kobune, Yasushi Sato, Tetsuji Takayama, T Matsunaga and Y Niitsu :
Augmentation of Antitumor Effects of p53 Gene Therapy by Combination with HDAC Inhibitor.,
Cancer Biology & Therapy, Vol.4, No.4, 421-428, 2005.

(要約): We have previously shown that the HDAC inhibitors (HDACI) activate the p53 molecule through acetylation of 320 and 373 lysine residues, upregulate PIG3 and NOXA and induce apoptosis in cancer cells expressing wild and pseudo-wild type p53 genes (Terui T, et al. Cancer Res 2003; 63:8948-54). It has also been reported that expression of the Coxsackie adenovirus receptor and subsequent transfection efficiency of the adenovirus in cancer cells were enhanced by HDACI treatment. In this study, we extended these observations to explore the combination effect of adenoviral vector carrying wild type p53 (Ad-p53) gene therapy with a HDACI, sodium butyrate (SB), on xenografted human gastric cancer cells (KATO-III) and hepatocellular carcinoma cells (HuH7) in nude mice. We first confirmed an increased expression of Coxsackie adenovirus receptors with an associated increment of transgene (X-gal) expression by SB treatment in KATO-III cells. We then injected Ad-p53 into subcutaneous tumors of KATO-III and HuH7 combined with intraperitoneal administration of SB and found a significantly higher growth suppressive effect than single treatments of each. Even a complete regression of tumors was observed in three of five mice treated with this combination while with single treatment no tumor regression was observed. Tumors treated with the combination showed higher numbers of TUNEL positive cells than those treated with a single modality. Moreover, necrotic changes were more evident in tumors treated with the combination than separately, a compatible finding to the observation that vascularity revealed by CD34 staining was poorer in tumors treated with the combination than those treated with p53 gene or SB alone. This was further supported by the finding that BAI-1 (brain specific angiogenesis inhibitor-1), an inhibitor of vascularization, was induced by SB treatment in KATO-III and HuH7 cells transfected with Ad-p53. Thus SB was shown to be an efficient potentiator of p53 gene therapy for cancer.
(キーワード): Adenoviridae / Animals / Butyrates / Carcinoma, Hepatocellular / Cell Line, Tumor / Cell Proliferation / Gene Therapy / Genes, p53 / Histone Deacetylase Inhibitors / Humans / Liver Neoplasms / Mice / Mice, Nude / Neoplasm Transplantation / Stomach Neoplasms / Transplantation, Heterologous / Tumor Suppressor Protein p53
(出版サイトへのリンク): ● Publication site (DOI): 10.4161/cbt.4.4.1620
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15846102; ● Search Scopus @ Elsevier (PMID): 15846102; ● Search Scopus @ Elsevier (DOI): 10.4161/cbt.4.4.1620

(DOI: 10.4161/cbt.4.4.1620, PubMed: 15846102) Yasushi Sato, H Araki, J Kato, K Nakamura, Y Kawano, M Kobune, T Sato, K Miyanishi, Tetsuji Takayama, M Takahashi, R Takimoto, S Iyama, T Matsunaga, S Ohtani, A Matsuura, H Hamada and Y Niitsu :
Human mesenchymal stem cells xenografted directly to rat liver differentiated into human hepatocytes without fusion.,
Blood, Vol.106, No.2, 756-763, 2005.

(要約): Hepatic transdifferentiation of bone marrow cells has been previously demonstrated by intravenous administration of donor cells, which may recirculate to the liver after undergoing proliferation and differentiation in the recipient's bone marrow. In the present study, to elucidate which cellular components of human bone marrow more potently differentiate into hepatocytes, we fractionated human bone marrow cells into mesenchymal stem cells (MSCs), CD34+ cells, and non-MSCs/CD34- cells and examined them by directly xenografting to allylalcohol (AA)-treated rat liver. Hepatocyte-like cells, as revealed by positive immunostaining for human-specific alpha-fetoprotein (AFP), albumin (Alb), cytokeratin 19 (CK19), cytokeratin 18 (CK18), and asialoglycoprotein receptor (AGPR), and by reverse transcription-polymerase chain reaction (RT-PCR) for expression of AFP and Alb mRNA, were observed only in recipient livers with MSC fractions. Cell fusion was not likely involved since both human and rat chromosomes were independently identified by fluorescence in situ hybridization (FISH). The differentiation appeared to follow the process of hepatic ontogeny, reprogramming of gene expression in the genome of MSCs, as evidenced by expression of the AFP gene at an early stage and the albumin gene at a later stage. In conclusion, we have demonstrated that MSCs are the most potent component in hepatic differentiation, as revealed by directly xenografting into rat livers.
(キーワード): Albumins / Animals / Antigens, CD34 / Asialoglycoprotein Receptor / Cell Count / Cell Differentiation / Female / Gene Expression / Hepatocytes / Humans / Immunohistochemistry / In Situ Hybridization, Fluorescence / Keratins / Liver / Membrane Fusion / Mesenchymal Stem Cell Transplantation / Mesenchymal Stem Cells / RNA, Messenger / Rats / Rats, Sprague-Dawley / Transplantation, Heterologous / alpha-Fetoproteins
(出版サイトへのリンク): ● Publication site (DOI): 10.1182/blood-2005-02-0572
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15817682; ● Search Scopus @ Elsevier (PMID): 15817682; ● Search Scopus @ Elsevier (DOI): 10.1182/blood-2005-02-0572

(DOI: 10.1182/blood-2005-02-0572, PubMed: 15817682) Kunihiro Takanashi, Yoshimitsu Onodera, Shigeyuki Fujii, Yoshiki Nishibori, Norihiro Takayanagi, Shinya Minami, Takahiro Kogawa, Hiroyuki Nagashima, Abe Seiichiro, Yasuhiro Nagaoka, Masayoshi Horimoto, Kohichi Takada, Yasushi Sato and Yoshiro Niitsu :
[A case of signet ring cell carcinoma of the stomach discovered by abdominal wall metastasis].,
The Japanese Journal of Gastro-enterology, Vol.102, No.4, 459-465, 2005.

(キーワード): Abdominal Neoplasms / Abdominal Wall / Aged / Carcinoma, Signet Ring Cell / Humans / Male / Stomach Neoplasms
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16004352; ● Search Scopus @ Elsevier (PMID): 16004352

(PubMed: 16004352) Yasushi Sato, Tetsuji Takayama, Eriko Waga, Tamotsu Sagawa, Tetsuro Okamoto, Koji Miyanishi, Tsutomu Sato, Rishu Takimoto, Yasuhiro Sato, Yoshimi Sato, Takatomi Oku, Hironobu Araki, Kouichi Takada, Kunihiro Takanashi, Junji Kato and Yoshiro Niitsu :
[A family of attenuated familial adenomatous polyposis (AFAP)].,
The Japanese Journal of Gastro-enterology, Vol.102, No.4, 453-458, 2005.

(キーワード): Adenomatous Polyposis Coli / Aged / Female / Genes, APC / Humans / Male / Middle Aged
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16004351; ● Search Scopus @ Elsevier (PMID): 16004351

(PubMed: 16004351) K Yamaguchi, H Shibuya, K Sasaki, K Takashima, Yasushi Sato, Y Arimura, Tetsuji Takayama, Itsuro Endo, Y Shinomura, Y Niitsu and K Hirata :
Clinical evaluation of laparoscopy-assisted distal gastrwctomy for early gastric cancer.,
Tumor Research, Vol.40, 37-45, 2005. Tamotsu Sagawa, Minoru Takahashi, Tsutomu Sato, Yasushi Sato, Yue Lu, Tetsuya Sumiyoshi, Yasuyuki Yamada, Satoshi Iyama, Junki Fukaura, Katsunori Sasaki, Hirofumi Hamada, Koji Miyanishi, Tetsuji Takayama, Junji Kato and Yoshiro Niitsu :
Prolonged survival of mice with multiple liver metastases of human colon cancer by intravenous administration of replicable E1B-55K-deleted adenovirus with E1A expressed by CEA promoter.,
Molecular Therapy, Vol.10, No.6, 1043-1050, 2004.

(要約): Liver is the most preferential site for metastasis of colon cancer. We, in the present study, constructed a self-replicable adenovirus in which E1A is driven by a CEA promoter and E1B-55K is deleted from the E1B region (AdCEAp/Rep) and examined its effects on multiple metastases of a human colon cancer cell in a mouse xenograft model. We first showed effective replication of the virus in various CEA-producing human colon cancer cells (M7609, HT-29) and subsequent lysis of the infected cells in vitro. We then demonstrated that a single intratumoral injection of the virus (1 x 10(8) PFU/100 microl) induced a complete regression of subcutaneous tumors (M7609) inoculated into nude mice. Further, we demonstrated that systemic administration of the virus (1 x 10(8) PFU/100 microl) through the tail vein to nude mice, which 1 week prior had been inoculated with tumor cells (colon carcinoma cell line HT-29) via the spleen and showed apparent multiple metastases in the liver, effectively suppressed the metastasis formation. The mean survival time of the treated mice was significantly longer than that of the controls. Thus, the systemic administration of AdCEAp/Rep was considered to be effective on multiple liver metastases of CEA-positive colon cancer in a xenograft model.
(キーワード): Adenoviridae / Adenovirus E1A Proteins / Adenovirus E1B Proteins / Animals / Carcinoembryonic Antigen / Colonic Neoplasms / Disease Models, Animal / Female / Gene Deletion / Genetic Therapy / Hepatocytes / Humans / Infusions, Intravenous / Liver Neoplasms / Mice / Neoplasm Transplantation / Promoter Regions, Genetic / Skin Neoplasms / Survival Rate / Time Factors / Tumor Cells, Cultured / Virus Replication
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.ymthe.2004.08.023
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15564136; ● Search Scopus @ Elsevier (PMID): 15564136; ● Search Scopus @ Elsevier (DOI): 10.1016/j.ymthe.2004.08.023

(DOI: 10.1016/j.ymthe.2004.08.023, PubMed: 15564136) Tsutomu Sato, Takuya Matsunaga, Masaya Kida, Kazuhiro Morii, Takuro Machida, Yutaka Kawano, Kiminori Nakamura, Kageaki Kuribayashi, Kohichi Takada, Satoshi Iyama, Yasushi Sato, Tetsuji Takayama, Minoru Takahashi, Junji Kato, Manabu Chokki and Yoshiro Niitsu :
Interleukin-11 as an osteoprotegerin-inducing factor in culture medium of blastic cells from a patient with acute megakaryocytic leukemia complicated with osteosclerosis.,
American Journal of Hematology, Vol.77, No.1, 62-66, 2004.

(要約): We came across a rare case of acute megakaryocytic leukemia, the clinical course of which was relatively chronic and nonaggressive. This case was complicated with generalized severe osteosclerosis (OS). The medium in which blastic cells from the patient were cultured showed a strong activity to enhance the expression of an osteosclerotic cytokine, osteoprotegerin (OPG), as revealed by real-time quantitative RT-PCR and Western blot analysis. The OPG-inducing activity of the culture medium was neutralized by the anti-interleukin-11 (IL-11) antibody. These results indicate that IL-11 produced by the blasts was a causative factor of the OS observed in this patient.
(キーワード): Adult / Blast Crisis / Glycoproteins / Humans / Interleukin-11 / Leukemia, Megakaryoblastic, Acute / Male / Osteoprotegerin / Osteosclerosis / Receptors, Cytoplasmic and Nuclear / Receptors, Tumor Necrosis Factor / Tumor Cells, Cultured / Up-Regulation
(出版サイトへのリンク): ● Publication site (DOI): 10.1002/ajh.20141
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15307108; ● Search Scopus @ Elsevier (PMID): 15307108; ● Search Scopus @ Elsevier (DOI): 10.1002/ajh.20141

(DOI: 10.1002/ajh.20141, PubMed: 15307108) A Nobuoka, Tetsuji Takayama, K Miyanishi, T Sato, T Hayashi, T Kukitsu, K Takanashi, Yasushi Sato, M Takahashi, T Okamoto, T Matsunaga, J Kato, M Oda, T Azuma and Y Niitsu :
Glutathione S-transferase P1-1 protects aberrant crypt foci from apoptosis induced by deoxycholic acid.,
Gastroenterology, Vol.127, No.2, 428-443, 2004.

(要約): Aberrant crypt foci, precursors of colonic adenoma, are frequently positive for glutathione-S-transferase P1-1. Because deoxycholic acid is an apoptosis-inducing xenobiotic in the colon, we examined the possibility that aberrant crypt foci, through the cytoprotecting function of glutathione-S-transferase P1-1, resist deoxycholic acid-induced apoptosis, thereby surviving to become adenomas and subsequently cancer. Glutathione-S-transferase P1-1 or cyclooxygenase-2 expression and the percentage of apoptotic cells in aberrant crypt foci were examined by immunohistochemistry and by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling, respectively. Glutathione-S-transferase P1-1 was transfected into colon cancer cells (M7609) and human lung fibroblasts, and deoxycholic acid-induced apoptosis was evaluated by a dye-uptake assay and flow cytometry. Binding of deoxycholic acid to glutathione-S-transferase P1-1 was analyzed by circular dichroism and immunoprecipitation. Caspase activities were determined by colorimetric protease assay, and sulindac binding to glutathione-S-transferase P1-1 was determined by inhibition assay of glutathione-S-transferase P1-1 activity. Aberrant crypt foci showed positive immunostaining for glutathione-S-transferase P1-1 but negative staining for cyclooxygenase-2. The percentage of apoptotic cells in aberrant crypt foci was significantly lower than in healthy epithelium, and the difference became more apparent with deoxycholic acid treatment. The impaired sensitivity of aberrant crypt foci to deoxycholic acid was restored by the glutathione-S-transferase P1-1-specific inhibitor gamma-glutamyl-S-(benzyl)cysteinyl-R-phenylglycine diethylester. By transfection of glutathione-S-transferase P1-1, M7609 cells became more resistant to deoxycholic acid-induced apoptosis than mock transfectants. Direct binding of glutathione-S-transferase P1-1 to deoxycholic acid was proven by circular dichroism and by immunoprecipitation. The aberrant crypt foci in adenoma patients treated with sulindac, which was shown to bind to glutathione-S-transferase P1-1, underwent apoptosis in 4 days and mostly regressed in 2-3 months. Glutathione-S-transferase P1-1 protects aberrant crypt foci from deoxycholic acid-induced apoptosis and may play a pivotal role in early colon carcinogenesis.
(キーワード): Adenoma / Antineoplastic Agents / Apoptosis / Cell Line, Tumor / Colonic Neoplasms / Cyclooxygenase 2 / Deoxycholic Acid / Detergents / Enzyme Inhibitors / Fibroblasts / Gene Expression Regulation, Enzymologic / Gene Expression Regulation, Neoplastic / Glutathione / Glutathione Transferase / Humans / Intestinal Mucosa / Isoenzymes / Lung / Membrane Proteins / Prostaglandin-Endoperoxide Synthases / RNA, Messenger / Sulindac / Transfection
(出版サイトへのリンク): ● Publication site (DOI): 10.1053/j.gastro.2004.05.021
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15300575; ● Search Scopus @ Elsevier (PMID): 15300575; ● Search Scopus @ Elsevier (DOI): 10.1053/j.gastro.2004.05.021

(DOI: 10.1053/j.gastro.2004.05.021, PubMed: 15300575) Tsutomu Sato, Takuro Machida, Sho Takahashi, Satoshi Iyama, Yasushi Sato, Kageaki Kuribayashi, Kohichi Takada, Takatomi Oku, Yutaka Kawano, Tetsuro Okamoto, Rishu Takimoto, Takuya Matsunaga, Tetsuji Takayama, Minoru Takahashi, Junji Kato and Yoshiro Niitsu :
Fas-mediated apoptosome formation is dependent on reactive oxygen species derived from mitochondrial permeability transition in Jurkat cells.,
The Journal of Immunology, Vol.173, No.1, 285-296, 2004.

(要約): Generation of reactive oxygen species (ROS) and activation of caspase cascade are both indispensable in Fas-mediated apoptotic signaling. Although ROS was presumed to affect the activity of the caspase cascade on the basis of findings that antioxidants inhibited the activation of caspases and that the stimulation of ROS by itself activated caspases, the mechanism by which these cellular events are integrated in Fas signaling is presently unclear. In this study, using human T cell leukemia Jurkat cells as well as an in vitro reconstitution system, we demonstrate that ROS are required for the formation of apoptosome. We first showed that ROS derived from mitochondrial permeability transition positively regulated the apoptotic events downstream of mitochondrial permeability transition. Then, we revealed that apoptosome formation in Fas-stimulated Jurkat cells was clearly inhibited by N-acetyl-L-cysteine and manganese superoxide dismutase by using both the immunoprecipitation and size-exclusion chromatography methods. To confirm these in vivo findings, we next used an in vitro reconstitution system in which in vitro-translated apoptotic protease-activating factor 1 (Apaf-1), procaspase-9, and cytochrome c purified from human placenta were activated by dATP to form apoptosome; the formation of apoptosome was markedly inhibited by reducing reagents such as DTT or reduced glutathione (GSH), whereas hydrogen peroxide prevented this inhibition. We also found that apoptosome formation was substantially impaired by GSH-pretreated Apaf-1, but not GSH-pretreated procaspase-9 or GSH-pretreated cytochrome c. Collectively, these results suggest that ROS plays an essential role in apoptosome formation by oxidizing Apaf-1 and the subsequent activation of caspase-9 and -3.
(キーワード): Antigens, CD95 / Apoptosis / Apoptotic Protease-Activating Factor 1 / Caspase 3 / Caspase 9 / Caspases / Cytochromes c / Humans / Hydrogen Peroxide / Jurkat Cells / Mitochondria / Permeability / Proteins / Reactive Oxygen Species
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15210786; ● Search Scopus @ Elsevier (PMID): 15210786

(PubMed: 15210786) Seiichiro Abe, Tetsuji Takayama, Hidetoshi Ohta, Rishu Takimoto, Tetsuro Okamoto, Yasushi Sato, Tomomi Nikaido, Kouhei Takizawa, Tomoyuki Abe and Yoshiro Niitsu :
Successful treatment with prostaglandin E1 of ischemic colitis complicated by colonic stricture.,
Gastrointestinal Endoscopy, Vol.60, No.1, 148-151, 2004.

(キーワード): Alprostadil / Colitis, Ischemic / Colon / Colonoscopy / Coloring Agents / Constriction, Pathologic / Female / Humans / Indocyanine Green / Infusions, Intravenous / Intestinal Mucosa / Middle Aged / Regional Blood Flow / Vasodilator Agents
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15229451; ● Search Scopus @ Elsevier (PMID): 15229451

(PubMed: 15229451) Takatomi Oku, Tetsuji Takayama, Yasuhiro Sato, Yasushi Sato, Koichi Takada, Tsuyoshi Hayashi, Minoru Takahashi, Mitsugu Kuroda, Junji Kato and Yoshiro Niitsu :
A case of Gardner syndrome with a mutation at codon 1556 of APC: a suggested case of genotype-phenotype correlation in dental abnormality.,
European Journal of Gastroenterology & Hepatology, Vol.16, No.1, 101-105, 2004.

(要約): A 25-year-old man with suspected Gardner syndrome was introduced to our hospital by a dentist who, during examination of the patient, had found dental dysplasias and multiple osteomas of the jaw. Radiographs, endoscopy and biopsies revealed adenomatous polyposis of the colon. Genetic analysis of peripheral lymphocytes revealed a one-base deletion at codon 1556 in exon 15 of APC, which caused a frame shift and a premature stop at codon 1564. The pedigree analysis demonstrated five patients in his family who presented with dental abnormality and osteomas in addition to adenomatous polyposis of the colon. Although the relationship between the location of APC mutations and dental abnormalities remains controversial, this case supports the hypothesis that a mutation at around codon 1556 of APC is closely associated with dental abnormality and osteomas.
(キーワード): Adult / Bone Neoplasms / Codon / Colonic Polyps / Gardner Syndrome / Genes, APC / Genotype / Humans / Jaw Neoplasms / Male / Mutation / Osteoma / Pedigree / Phenotype / Tooth Abnormalities
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15095859; ● Search Scopus @ Elsevier (PMID): 15095859

(PubMed: 15095859) Hiroki Chiba, Rishu Takimoto, Yasushi Sato, Tetsuji Takayama, Junji Kato, Yasuo Hirayama, Sumio Sakamaki, Tomohiko Matsuyama, Shungo Murakami and Yoshiro Niitsu :
Gamma/delta T-cell lymphoma of duodenal bulb: a case report.,
Gastrointestinal Endoscopy, Vol.58, No.4, 616-620, 2003.

(キーワード): Aged / Duodenal Neoplasms / Endoscopy, Gastrointestinal / Female / Humans / Lymphoma, T-Cell / Polymerase Chain Reaction / Receptors, Antigen, T-Cell, gamma-delta / T-Lymphocyte Subsets
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 14520306; ● Search Scopus @ Elsevier (PMID): 14520306

(PubMed: 14520306) Seiya Hagiwara, Kiminori Nakamura, Hirofumi Hamada, Katsunori Sasaki, Yoshinori Ito, Kageaki Kuribayashi, Tsutomu Sato, Yasushi Sato, Minoru Takahashi, Katsuhisa Kogawa, Junji Kato, Takeshi Terui, Tetsuji Takayama, Takuya Matsunaga, Kazunari Taira and Yoshiro Niitsu :
Inhibition of type I procollagen production by tRNAVal CTE-HSP47 ribozyme.,
The Journal of Gene Medicine, Vol.5, No.9, 784-794, 2003.

(要約): We suggest applicability of this ribozyme as a new modality for antifibrosis therapy.
(キーワード): Antisense Elements (Genetics) / Base Sequence / Collagen Type I / Gene Expression Regulation / HSP47 Heat-Shock Proteins / Heat-Shock Proteins / Humans / Luciferases / Molecular Sequence Data / Plasmids / RNA / RNA, Catalytic / RNA, Transfer, Val / Recombinant Fusion Proteins / Regulatory Sequences, Nucleic Acid / Response Elements
(出版サイトへのリンク): ● Publication site (DOI): 10.1002/jgm.404
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12950069; ● Search Scopus @ Elsevier (PMID): 12950069; ● Search Scopus @ Elsevier (DOI): 10.1002/jgm.404

(DOI: 10.1002/jgm.404, PubMed: 12950069) Tamotsu Sagawa, Yasushi Tsuji, Norihiro Takayanagi, Yasuo Hirayama, Sumio Sakamaki, Hiroki Chiba, Takaharu Nakajima, Satoshi Iyama, Takatomi Oku, Tetsuya Sumiyoshi, Yasushi Sato, Minoru Takahashi, Tetsuji Takayama and Yoshiro Niitsu :
[A case responding to weekly paclitaxel (TXL) therapy as third line chemotherapy for scirrhous type gastric cancer].,
Japanese Journal of Cancer and Chemotherapy, Vol.30, No.5, 707-710, 2003.

(要約): A 67-year-old female was admitted to our hospital in May, 2001 for examination. She was diagnosed with advanced gastric cancer that was inoperable due to peritoneal dissemination. Seventeen courses of sequential MTX and 5-FU therapy, and 2 courses of TS-1 plus CDDP were carried out. A partial response (PR) and prolonged NC were obtained after these chemotherapies. However, pleural effusion and ascites appeared again, and we diagnosed progressive disease. As a third line chemotherapy for this patient, paclitaxel (TXL) was administered. Treatment consisted of two 3-week courses of paclitaxel 70 mg per m2 on day 1 of each week, with a 1-week break between the courses. Two weeks after the start of this therapy, pleural effusion and ascites had completely disappeared. Paclitaxel is considered to be promising for advanced gastric cancers, as second or third line chemotherapy with paclitaxel for patients with inoperable gastric cancer seems to be effective in improving QOL.
(キーワード): Adenocarcinoma, Scirrhous / Aged / Antineoplastic Agents, Phytogenic / Ascites / Drug Administration Schedule / Female / Humans / Paclitaxel / Pleural Effusion / Stomach Neoplasms
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12795107; ● Search Scopus @ Elsevier (PMID): 12795107

(PubMed: 12795107) Tamotsu Sagawa, Yasushi Tsuji, Norihiro Takayanagi, Yasuo Hirayama, Sumio Sakamaki, Hiroki Chiba, Satoshi Iyama, Takatomi Oku, Yasushi Sato, Minoru Takahashi, Tetsuji Takayama and Yoshiro Niitsu :
[A case of irinotecan-resistant colon cancer responding to chronotherapy with oxaliplatin, 5-FU, l-LV].,
Japanese Journal of Cancer and Chemotherapy, Vol.30, No.4, 537-543, 2003.

(要約): We report a case of irinotecan-resistant colon cancer responding to chronotherapy with oxaliplatin (L-OHP), 5-FU, l-LV (l-Leucovorin). A 72-year-old man was examined at a certain hospital because of constipation and appetite loss. Chest computed tomography (CT) revealed lung metastases, and abdominal CT revealed liver metastases. He was then referred to our hospital. A colonoscopy revealed type 2 tumor in the colon, at the hepatic flexure. We diagnosed adenocarcinoma of the colon with metastases to the liver and lung. Resection of the primary lesion was performed, and chemotherapy consisting of systemic administration of CPT-11, 5-FU and l-LV was performed. After 2 courses of combined treatment with CPT-11/5-FU/l-LV, CT revealed considerable reduction of the metastatic tumors. However, after 3 courses of combined treatment, progressive disease was observed and new brain and bone metastases were detected. We imported and used a non-approved/pending drug, oxaliplatin from the Remedy and Health Corporation, with informed consent from the patient and his family and our clinical ethics committee. Chronotherapeutic schedules have been performed, from which the safety and activity of oxaliplatin against advanced colorectal cancer was reported. Our patient received a 5-day course of chronomodulated 5-FU and l-LV (750 and 300 mg/body/day, respectively; peak delivery rate at AM 4:00 hours) with L-OHP on the first day of each course (100 mg/body, as a 6-hour infusion). Each course was again repeated every 21 days. A partial response was observed in the liver and lung metastases. These results indicate that chronomodulated 5-FU and LV with L-OHP therapy could be an effective regimen for cases of irinotecan-resistant colon cancer.
(キーワード): Aged / Antineoplastic Combined Chemotherapy Protocols / Bone Neoplasms / Camptothecin / Chronotherapy / Colonic Neoplasms / Drug Evaluation / Drug Resistance, Neoplasm / Fluorouracil / Humans / Leucovorin / Liver Neoplasms / Lung Neoplasms / Male / Organoplatinum Compounds
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12722689; ● Search Scopus @ Elsevier (PMID): 12722689

(PubMed: 12722689) Hiroyuki Ohnuma, Yasushi Sato, Tetsuji Takayama, Rishu Takimoto, Tomoyuki Abe, Seiya Hagiwara, Takehiro Kukitsu, Atsushi Nobuoka, Tsutomu Sato, Katsuhisa Kogawa, Junji Kato and Yoshiro Niitsu :
Esophageal cancer complicated by cytomegalovirus esophagitis during chemoradiotherapy: case report.,
Gastrointestinal Endoscopy, Vol.57, No.4, 622-626, 2003.

(キーワード): Antineoplastic Combined Chemotherapy Protocols / Antiviral Agents / Cytomegalovirus Infections / Esophageal Neoplasms / Esophagitis / Esophagus / Female / Fever of Unknown Origin / Ganciclovir / Humans / Immunocompromised Host / Immunohistochemistry / In Situ Hybridization / Middle Aged / Mucous Membrane / Radiotherapy Dosage / Sensitivity and Specificity
(出版サイトへのリンク): ● Publication site (DOI): 10.1067/mge.2003.150
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12665790; ● Search Scopus @ Elsevier (PMID): 12665790; ● Search Scopus @ Elsevier (DOI): 10.1067/mge.2003.150

(DOI: 10.1067/mge.2003.150, PubMed: 12665790) T Sagawa, Tetsuji Takayama, T Oku, T Hayashi, H Ota, T Okamoto, H Muramatsu, S Katsuki, Yasushi Sato, J Kato and Y Niitsu :
Argon plasma coagulation for successful treatment of early gastric cancer with intramucosal invasion.,
Gut, Vol.52, No.3, 334-339, 2003.

(要約): APC is a safe and effective modality for treatment of early gastric cancer with intramucosal invasion untreatable by surgical resection or EMR. However, further observations are necessary to determine the long term prognosis of patients undergoing this treatment.
(キーワード): Adenocarcinoma / Aged / Aged, 80 and over / Animals / Electrocoagulation / Female / Follow-Up Studies / Gastric Mucosa / Gastroscopy / Humans / Male / Middle Aged / Neoplasm Invasiveness / Stomach Neoplasms / Swine / Treatment Outcome
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12584212; ● Search Scopus @ Elsevier (PMID): 12584212

(PubMed: 12584212) T Sato, T Terui, K Kogawa, Y Nagaoka, Yasushi Sato, S Iyama, K Takada, S Hagiwara, S Takahashi, T Oku, T Matsunaga, M Takahashi, J Kato, S Sakamaki, T Torigoe, N Sato, M Hirayama and Y Niitsu :
A case of true malignant histiocytosis: identification of histiocytic origin with use of immunohistochemical and immunocytogenetic methods.,
Annals of Hematology, Vol.81, No.5, 285-288, 2002.

(要約): We report here an autopsy case of true malignant histiocytosis. The patient was a 67-year-old woman who exhibited fever, wasting, hepatosplenomegaly, and progressive pancytopenia. The bone marrow aspiration disclosed hemophagocytosing cells, which resembled histiocytes. The molecular analysis did not show the clonal gene rearrangement of T-cell receptor or immunoglobulin heavy chain. Although the patient had been started on methylprednisolone pulse therapy and chemotherapy with etoposide, she died from cerebral hemorrhage. The autopsy specimens of spleen and liver showed extensive infiltration of atypical cells, for which histiocytic origin was identified with an immunohistochemical method using monoclonal antibodies against CD11c, CD68, macrophage colony-stimulating factor (M-CSF), M-CSF receptor, lysozyme, antitrypsin and alpha1-antichymotrypsin. Recent investigations have disclosed that in most cases diagnosed as malignant histiocytosis, hemophagocytosis was reactive and not evoked by histiocytic malignancy. True malignant histiocytosis, for which histiocytic origin is confirmed, is extremely rare.
(キーワード): Aged / Antibodies, Monoclonal / Bone Marrow / Cell Line / Cytogenetic Analysis / Fatal Outcome / Female / Histiocytic Sarcoma / Humans / Immunohistochemistry / Liver / Spleen
(出版サイトへのリンク): ● Publication site (DOI): 10.1007/s00277-002-0446-7
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12029539; ● Search Scopus @ Elsevier (PMID): 12029539; ● Search Scopus @ Elsevier (DOI): 10.1007/s00277-002-0446-7

(DOI: 10.1007/s00277-002-0446-7, PubMed: 12029539) G Kuroiwa, Tetsuji Takayama, Yasushi Sato, Y Takahashi, T Fujita, A Nobuoka, T Kukitsu, J Kato, S Sakamaki and Y Niitsu :
Primary intestinal lymphangiectasia successfully treated with octreotide.,
Journal of Gastroenterology, Vol.36, No.2, 129-132, 2001.

(要約): A 21-year-old man with diarrhea and edema was admitted to our hospital and diagnosed with protein-losing enteropathy caused by primary intestinal lymphangiectasia. He was placed, in turn, on a low-fat diet, an elemental diet, and, subsequently, fasting therapy with total parenteral nutrition (TPN) support. However, his symptoms were not relieved, but, rather were exacerbated. On the 45th day of hospitalization, octreotide therapy was initiated. After 2 weeks of treatment, his clinical symptoms, as well as hypoproteinemia and hypoalbuminemia, gradually became alleviated. The improvement was confirmed in terms of scintigraphy, endoscopy, and histology of the duodenum. The patient remained healthy until 6 months after the commencement of octreotide treatment, when he discontinued octreotide at his own discretion, at which point the symptoms recurred. Resumption of the drug, however, again brought about remission, which has continued until the present, March 2000. Thus, octreotide therapy is one modality which may be useful for refractory primary intestinal lymphangiectasia.
(キーワード): Adult / Gastrointestinal Agents / Humans / Lymphangiectasis, Intestinal / Male / Octreotide
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11227670; ● Search Scopus @ Elsevier (PMID): 11227670

(PubMed: 11227670) H Fujiwara, N Yamauchi, Yasushi Sato, K Sasaki, M Takahashi, T Okamoto, T Sato, S Iyama, Y Koshita, M Hirayama, H Yamagishi and Y Niitsu :
Synergistic suppressive effect of double transfection of tumor necrosis factor-alpha and interleukin 12 genes on tumorigenicity of Meth-A cells.,
Gann : Japanese Journal of Cancer Research, Vol.91, No.12, 1296-1302, 2000.

(要約): Tumor necrosis factor-alpha (TNF-alpha) and interleukin 12 (IL-12), both potent antitumor cytokines, are known to be involved in the host's antitumor immune surveillance in tumor bearers, via different mechanisms. The former enhances the activities of dendritic cells, natural killer / lymphocyte-activated killer (NK / LAK) and cytotoxic T lymphocyte (CTL), while the latter induces Th1-type cellular immunity and enhances the activities of natural killer T (NKT), NK / LAK and CTL. In the present study, in the expectation of synergistic actions of these cytokines in stimulating the host's immune responses, we investigated the feasibility of a cancer vaccine involving double transfection with both genes in a murine model. The expression of major histocompatibility complex (MHC) class I, class II and B7.1 on the surface of the double transfectants was enhanced as revealed by FACS analysis. A significant decrease in tumorigenicity was observed in mice inoculated with the double transfectants. Cytotoxicity assay revealed that the activities of NK / LAK and CTL from spleens of mice bearing the double transfectants were enhanced. The induction of tumor-specific immunity was confirmed by rechallenge with parental Meth-A cells in mice that had rejected the double transfectants. Thus, double transfection of TNF-alpha and IL-12 genes was considered to bring about synergistic suppressive effects on the tumorigenicity of transfectants through the activation of killer cells by produced cytokines and the enhancement of expression of MHC class I, II and B7.1 molecules.
(キーワード): Adenocarcinoma / Animals / Antigens, CD80 / Colonic Neoplasms / Cytotoxicity, Immunologic / Fibrosarcoma / Histocompatibility Antigens Class I / Histocompatibility Antigens Class II / Interleukin-12 / Killer Cells, Lymphokine-Activated / Killer Cells, Natural / Lymphoma / Mice / Mice, Inbred BALB C / Recombinant Proteins / T-Lymphocytes, Cytotoxic / Transfection / Tumor Necrosis Factor-alpha
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11123429; ● Search Scopus @ Elsevier (PMID): 11123429

(PubMed: 11123429) Y Nishihori, N Yamauchi, K Kuribayashi, 佐藤康史, K Morii, Y Hirayama, S Sakamaki, H Honma, N Suzuki, T Kudo, Y Niitsu :
[Severe hemolysis and SIADH-like symptoms induced by vincristine in an ALL patient with liver cirrhosis].,
臨床血液, Vol.41, No.11, 1231-1237, 2000年.

(要約): An 11-year-old boy was diagnosed as having acute lymphoblastic leukemia (ALL, L1) in 1987 and underwent treatment with an ALL high-risk protocol (prednisolone, vincristine (VCR), daunorubicin, 1-asparaginase), which resulted in complete remission. In 1990 he developed chronic hepatitis C and received interferon therapy. In December 1994, ALL recurred, and the patient was treated with VCR. He subsequently developed severe hemolysis (Hb 12.5 g/dl-->6.8 g/dl) with increases of indirect bilirubin, AST, and LDH. Furthermore, symptoms resembling a syndrome of inappropriate secretion of ADH (SIADH) and DIC developed. Upon incubation of the patient's red blood cells with VCR in vitro, extreme deformity of the cells was observed. These findings suggested that splenomegaly, due to liver cirrhosis which had developed rapidly from chronic hepatitis C while the patient was in an immunosuppressed state induced by anticancer drugs, had trapped the deformed red blood cells and resulted in severe hemolysis. The patient died on the 165th day after admission due to liver failure.
(キーワード): Adolescent / Antineoplastic Agents, Phytogenic / Antineoplastic Combined Chemotherapy Protocols / Asparaginase / Daunorubicin / Hemolysis / Hepatitis C / Humans / Inappropriate ADH Syndrome / Liver Cirrhosis / Male / Precursor Cell Lymphoblastic Leukemia-Lymphoma / Prednisolone / Vincristine
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11193445; ● Search Scopus @ Elsevier (PMID): 11193445

(PubMed: 11193445) Yasushi Sato, N Yamauchi, M Takahashi, K Sasaki, J Fukaura, H Neda, S Fujii, M Hirayama, Y Itoh, Y Koshita, K Kogawa, J Kato, S Sakamaki and Y Niitsu :
In vivo gene delivery to tumor cells by transferrin-streptavidin-DNA conjugate.,
The FASEB journal, Vol.14, No.13, 2108-2118, 2000.

(要約): To target disseminated tumors in vivo, transgenes [beta-galactosidase gene, green fluorescence protein (GFP) gene, herpes simplex virus thymidine kinase (HSV-TK)] were conjugated to transferrin (Tf) by a biotin-streptavidin bridging, which is stoichiometrically controllable, and Tf receptor (Tf-R) affinity chromatography, which selects Tf conjugates with intact receptor bindings sites from reacting with the linker. Tf-beta-galactosidase plasmid conjugate thus constructed was specifically transfected to human erythroleukemia cells (K562) via Tf-R without the aid of any lysosomotropic agents. The transfection efficiency of the conjugate was superior to those of lipofection (1% staining) and retroviral vector (5%) and slightly lower than that of adenovirus (70%). The high level of expression with our conjugate was confirmed using other tumor cells (M7609, TMK-1) whereas in normal diploid cells (HEL), which express low levels of Tf-R, expression was negligible. When GFP gene conjugates were systemically administered through the tail vein to nude mice subcutaneously inoculated with tumor, expression of GFP mRNA was found almost exclusively in tumors and to a much lesser extent in muscles, whereas GFP revealed by fluorescence microscopy was detected only in the former. To exploit a therapeutic applicability of this method, suicide gene therapy using Tf-HSV-TK gene conjugate for massively metastasized k562 tumors in severe combined immune-deficient mice was conducted, and a marked prolongation of survival and significant reduction of tumor burden were confirmed. Thus, this method could also be used for gene therapy to disseminated tumors.
(キーワード): Animals / Biotin / Biotinylation / DNA / Drug Carriers / Gene Targeting / Genetic Therapy / Green Fluorescent Proteins / Humans / K562 Cells / Leukemia, Erythroblastic, Acute / Leukemia, Experimental / Luminescent Proteins / Mice / Neoplasm Metastasis / Plasmids / Simplexvirus / Streptavidin / Thymidine Kinase / Transferrin / beta-Galactosidase
(出版サイトへのリンク): ● Publication site (DOI): 10.1096/fj.99-1052com
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11023995; ● Search Scopus @ Elsevier (PMID): 11023995; ● Search Scopus @ Elsevier (DOI): 10.1096/fj.99-1052com

(DOI: 10.1096/fj.99-1052com, PubMed: 11023995) T Sato, K Kogawa, Y Hirayama, Yasushi Sato, A Nobuoka, K Kuribayashi, S Iyama, K Takada, S Hagiwara, S Takahashi, J Kato, S Sakamaki, S Ishigaki and Y Niitsu :
[Pure red cell aplasia induced by clomipramine hydrochloride in a patient with SLE].,
The Japanese Journal of Clinical Hematology, Vol.41, No.8, 648-652, 2000.

(要約): A 48-year-old woman, who had been suffering from systemic lupus erythematosus (SLE), developed normochromic normocytic anemia after receiving clomipramine hydrochloride. Her reticulocyte count was low, and a bone marrow aspirate revealed erythroid hypoplasia without involvement of other cell lines. Thus a diagnosis of pure red cell aplasia (PRCA) was made. The anemia gradually resolved following withdrawal of the drug. Although several drugs are known to cause PRCA, this is the first time that clomipramine hydrochloride has been reported to have such an effect. The underlying SLE in this case suggested the possible immunological pathogenesis of drug-induced PRCA.
(キーワード): Antidepressive Agents, Tricyclic / Clomipramine / Female / Humans / Lupus Erythematosus, Systemic / Middle Aged / Red-Cell Aplasia, Pure
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11020992; ● Search Scopus @ Elsevier (PMID): 11020992

(PubMed: 11020992) K Miyanishi, H Watanabe, S Hayashi, N Ban, M Horimoto, N Inui, Y Onodera, 佐藤康史, T Hayashi, T Fujita, I Oda, Y Niitsu :
[Spontaneous internal drainage of pancreatic pseudocyst with fistula to the common bile duct].,
日本消化器病学会雑誌, Vol.97, No.2, 213-217, 2000年.

(キーワード): Aged / Biliary Fistula / Cholangiopancreatography, Endoscopic Retrograde / Common Bile Duct Diseases / Humans / Male / Pancreatic Fistula / Pancreatic Pseudocyst / Remission, Spontaneous / Tomography, X-Ray Computed
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 10707594; ● Search Scopus @ Elsevier (PMID): 10707594

(PubMed: 10707594) T Sato, N Yamauchi, D Kobayashi, Yasushi Sato, C Mochizuki, C Hori, N Watanabe and Y Niitsu :
[Granulocyte colony stimulating factor (G-CSF) producing renal cell carcinoma].,
The Japanese Journal of Clinical Hematology, Vol.38, No.11, 1189-1193, 1997.

(要約): A 88-year-old male patient with G-CSF producing renal cell carcinoma is reported. The patient was admitted to our hospital complaining of macrohematureia. The laboratory examination showed marked leukocytosis of 18,200/microliter (neutrophil 92%) in the peripheral blood and high levels of G-CSF (120 pg/ml) in the serum. An abdominal CT scan revealed a right renal tumor. The neutrophil count rose to 38,700/microliter with increasing of tumor size. Histopathological diagnosis was renal cell carcinoma (Grade 3) and immunohistochemical staining using Histo anti-G-CSF antibody demonstrated cancer cells produced G-CSF. This is the second case of G-CSF producing renal cell carcinoma diagnosed by immunohistochemical staining in the literature.
(キーワード): Aged / Aged, 80 and over / Carcinoma, Renal Cell / Granulocyte Colony-Stimulating Factor / Humans / Immunohistochemistry / Kidney Neoplasms / Male
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 9423336; ● Search Scopus @ Elsevier (PMID): 9423336

(PubMed: 9423336) Yasushi Sato, Y Koshita, M Hirayama, T Matuyama, H Wakimoto, H Hamada and Y Nitsu :
Augmented antitumor effects of killer cells induced by tumor necrosis factor gene-transduced autologous tumor cells from gastrointestinal cancer patients.,
Human Gene Therapy, Vol.7, No.15, 1895-1905, 1996.

(要約): The purpose of this study was to determine the feasibility of a vaccine therapy using tumor necrosis factor (TNF) gene-transduced autologous tumor cells for the treatment of human gastrointestinal cancers, which tend to have lower immunogenicity than other cancers such as melanoma and renal cell carcinoma. We succeeded in establishing primary cultured tumor cells from 12/54 carcinomatous effusions (4 liver cancer patients, 5 gastric cancer patients, 1 pancreatic cancer patient, and 2 colon cancer patients) and in transducing the TNF gene to the tumor cells by using the retrovirus vector MFG-TNF. Even after irradiation, TNF production (0.3-3.5 U/ml per 10(6) cells per 72 hr) was confirmed for 10 of 12 transfectants, and the other two transduced cells were found to have approximately one TNF gene copy. In 7 of the 12 patients, the cytotoxic activity of killer cells to nontransduced autologous tumor cells incubated with these TNF gene transfectants was augmented. This activity was blocked with anti-HLA class I antibody or BrefeldinA (BFA), suggesting that the killer cells were cytotoxic T lymphocytes (CTL) and tumor antigens are presented with HLA class I molecules. Indeed, enhanced expression of HLA class I and/or ICAM-1 molecules on the surface of the TNF gene-transduced tumor cells were observed by fluorescence-activated cell sorting (FACS) analysis. Furthermore, natural killer (NK) and/or lymphokine-activated killer (LAK) activities determined by using K562 or Daudi cells as targets were also enhanced in some of these cases when they were incubated with TNF gene-transduced tumor cells. These findings indicate the feasibility of using TNF gene-transduced tumor cells as a vaccine in gastrointestinal cancer patients.
(キーワード): Carcinoma, Hepatocellular / Colorectal Neoplasms / Enzyme-Linked Immunosorbent Assay / Flow Cytometry / Gastrointestinal Neoplasms / Histocompatibility Antigens Class I / Humans / In Vitro Techniques / Intercellular Adhesion Molecule-1 / Killer Cells, Natural / Pancreatic Neoplasms / Transduction, Genetic / Tumor Cells, Cultured / Tumor Necrosis Factor-alpha
(出版サイトへのリンク): ● Publication site (DOI): 10.1089/hum.1996.7.15-1895
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 8894681; ● Search Scopus @ Elsevier (PMID): 8894681; ● Search Scopus @ Elsevier (DOI): 10.1089/hum.1996.7.15-1895

(DOI: 10.1089/hum.1996.7.15-1895, PubMed: 8894681) Y Koshita, Y Lu, S Fujii, H Neda, T Matsuyama, Yasushi Sato, Y Itoh, M Takahashi, J Kato and S Sakamaki :
Efficacy of TNF-alpha gene-transduced tumor cells in treatment of established in vivo tumor.,
International Journal of Cancer, Vol.63, No.1, 130-135, 1995.

(要約): The therapeutic effect of TNF gene-transduced mouse fibrosarcoma cells (Meth-A: C5) on pre-inoculated parental cells (Meth-A: M0) was studied. Subcutaneous (s.c.) transplantation of M0 cells into one flank of syngeneic BALB/c mice was followed by s.c. injection of irradiated MO or C5 into the opposite flank 1 week later. The initial M0 tumor (T-MO) completely regressed in C5-vaccinated mice, whereas in M0-vaccinated mice continuous growth of T-M0 was observed. When a similar experiment was carried out in SCID mice, no regression of T-MO was observed, suggesting that the tumor regression in BALB/c mice was not due to direct anti-tumor activity of TNF secreted from C5, but to systemic immunity. Regression of the rechallenged M0 tumor was observed in mice which had shown T-MO regression by C5 vaccination, but rechallenged Colon 26 cells (syngeneic to BALB/c mice) continued to grow, indicating a specific immunity to Meth-A cells). The systemic immunity evoked in C5-vaccinated mice was directly demonstrated by enhanced killer activities of LAK and CTL with a proliferation of T-cell population in their splenocytes. Abrogation of the therapeutic effect of C5 vaccination with anti-Thy 1 and anti-Lyt 2 also demonstrates the involvement of cellular immunity in tumor regression.
(キーワード): Animals / Cytotoxicity, Immunologic / Female / Flow Cytometry / Genetic Therapy / Immunity, Cellular / Killer Cells, Lymphokine-Activated / Lymphocyte Depletion / Mice / Mice, Inbred BALB C / Mice, SCID / Neoplasm Transplantation / Sarcoma, Experimental / T-Lymphocyte Subsets / T-Lymphocytes, Cytotoxic / Transduction, Genetic / Tumor Necrosis Factor-alpha
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 7558441; ● Search Scopus @ Elsevier (PMID): 7558441

(PubMed: 7558441)

MISC

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総説・解説

岡本耕一, 三井康裕, 吉本貴則, 藤本将太, 三橋威志, 上田浩之, 横山怜子, 川口智之, 影本開三, 喜田慶史, 中村文香, 佐藤康史, 春藤譲治, 坂東良美, 九嶋亮治, 高山哲治 :
遺伝性胃癌:病態解析と診断の進歩胃腺癌および近位胃ポリポーシス(GAPPS)を中心に.,
胃と腸, Vol.58, No.12, 1589-1601, 2023年12月. Yasushi Sato, Koichi Okamoto, Yoshifumi Kida, Yasuhiro Mitsui, Yutaka Kawano, Masahiro Sogabe, Hiroshi Miyamoto and Tetsuji Takayama :
Overview of Chemotherapy for Gastric Cancer.,
Journal of Clinical Medicine, Vol.12, No.4, 1336, Feb. 2023.

(要約): Gastric cancer (GC) is one of the most clinically challenging cancers worldwide. Over the past few years, new molecular-targeted agents and immunotherapy have markedly improved GC prognosis. Human epidermal growth factor receptor 2 (HER2) expression is a key biomarker in first-line chemotherapy for unresectable advanced GC. Further, the addition of trastuzumab to cytotoxic chemotherapy has extended the overall survival of patients with HER2-positive advanced GC. In HER2-negative GC, the combination of nivolumab, an immune checkpoint inhibitor, and a cytotoxic agent has been demonstrated to prolong the overall survival of GC patients. Ramucirumab and trifluridine/tipiracil, which are second- and third-line treatments for GC, and trastuzumab deruxtecan, an antibody-drug conjugate for HER2-positive GC, have been introduced in clinics. New promising molecular-targeted agents are also being developed, and combination therapy comprising immunotherapy and molecular-targeted agents is expected. As the number of available drugs increases, it is important to understand the target biomarkers and drug characteristics and select the optimal therapy for each patient. For resectable disease, differences in the extent of standard lymphadenectomy between Eastern and Western countries have led to different standard treatments: perioperative (neoadjuvant) and adjuvant therapy. This review aimed to summarize recent advances in chemotherapy for advanced GC.
(徳島大学機関リポジトリ): ● Metadata: 118894
(出版サイトへのリンク): ● Publication site (DOI): 10.3390/jcm12041336
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36835872; ● Search Scopus @ Elsevier (PMID): 36835872; ● Search Scopus @ Elsevier (DOI): 10.3390/jcm12041336

(徳島大学機関リポジトリ: 118894, DOI: 10.3390/jcm12041336, PubMed: 36835872) 寺前智史, 田中久美子, 岡本耕一, 佐藤康史, 六車直樹, 高山哲治 :
Cowden症候群(IV. 各論消化管ポリポーシス).,
日本臨牀, Vol.80, No.7, 241-246, 2022年7月. Yasushi Sato, Koichi Okamoto, Tomoyuki Kawaguchi, Fumika Nakamura, Hiroshi Miyamoto and Tetsuji Takayama :
Treatment Response Predictors of Neoadjuvant Therapy for Locally Advanced Gastric Cancer: Current Status and Future Perspectives.,
Biomedicines, Vol.10, No.7, 1614, Jul. 2022.

(要約): Neoadjuvant chemotherapy (NAC) for locally advanced gastric cancer (LAGC) has been recognized as an effective therapeutic option because it is expected to improve the curative resection rate by reducing the tumor size and preventing recurrence of micrometastases. However, for patients resistant to NAC, not only will operation timing be delayed, but they will also suffer from side effects. Thus, it is crucial to develop a comprehensive strategy and select patients sensitive to NAC. However, the therapeutic effect of NAC is unpredictable due to tumor heterogeneity and a lack of predictive biomarkers for guiding the choice of optimal preoperative treatment in clinical practice. This article summarizes the related research progress on predictive biomarkers of NAC for gastric cancer. Among the many investigated biomarkers, metabolic enzymes for cytotoxic agents, nucleotide excision repair, and microsatellite instability, have shown promising results and should be assessed in prospective clinical trials. Noninvasive liquid biopsy detection, including miRNA and exosome detection, is also a promising strategy.
(徳島大学機関リポジトリ): ● Metadata: 117415
(出版サイトへのリンク): ● Publication site (DOI): 10.3390/biomedicines10071614
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 35884916; ● Search Scopus @ Elsevier (PMID): 35884916; ● Search Scopus @ Elsevier (DOI): 10.3390/biomedicines10071614

(徳島大学機関リポジトリ: 117415, DOI: 10.3390/biomedicines10071614, PubMed: 35884916) 寺前智史, 田中久美子, 岡本耕一, 佐藤康史, 六車直樹, 高山哲治 :
【小腸疾患-診断・治療の最新動向-】消化管ポリポーシス Cowden症候群,
日本臨牀, Vol.80, 241-246, 2022年7月.

(キーワード): 胃腫瘍 *過誤腫症候群-多発性(診断) 食道腫瘍大腸腫瘍小腸腫瘍評価基準ヒト

佐藤康史, 高山哲治 :
(I章)消化管(上・下) 高齢者に対する癌治療,
消化器内科学レビュー, Vol.2022-'23, 131-138, 2022年7月.

(要約): <最近の動向とガイドライン>●2019年に本邦でも"高齢者のがん薬物療法ガイドライン"が発刊され，高齢者癌治療に対する関心の高まりがみられている．しかし，まだガイドラインに反映されるような十分な大規模研究によるエビデンスが報告されていなかったことから，先頃発刊された「胃癌治療ガイドライン2021」では，高齢の切除不能進行・再発胃癌症例に対しては，患者の状態良好(fit)であれば化学療法を行うことを強く推奨し，それ以外の場合は患者の状態にある無治療を含めた適切な治療選択を勧めるという記載にとどまっている．●一方，「高齢者のがん薬物療法ガイドライン」では，実臨床を反映させ，少し具体的に経口フッ化ピリミジン製剤とシスプラチンは併用せず，オキサリプラチンの併用を提案している．●2021年，英国から，高齢者胃癌における低用量化学療法レジメンの有効性を評価した初めての第III相試験であるGO2試験の結果が報告され，オキサリプラチン+カペシタビン(OX療法)の治療強度を下げることで，抗腫瘍効果に大きな影響を与えることなく，患者のQOLを改善できることが示され，今後の高齢者の胃癌薬物療法に大きな影響を与える結果と考えられる．●大腸癌においては，AVEX試験によりカペシタビンにベバシズマブを併用することでPFSが改善することが報告されて以来，様々な抗癌剤にベバシズマブを併用するレジメンや，比較的忍容性の高いレゴラフェニブやFTD/TPIなどの第II相試験が進められている段階である．したがって，「高齢者のがん薬物療法ガイドライン」では，高齢者切除不能進行再発大腸癌の初回化学療法においてベバシズマブの使用を提案するにとどまっている．一方，full doseのS-1に比べ減量したS-1とオキサリプラチンの併用療法の有効性を示したNORDIC9試験が報告されたことから，胃癌と同様に併用療法を適切に減量投与することが今後の傾向になるであろう．まだエビデンスは少ないが，免疫チェックポイント阻害薬(ICI)は，高齢の消化管癌患者に対するエビデンスも蓄積されつつあり，有望な選択肢となる可能性が高い．●各種ガイドラインにおいて，高齢者の薬物療法の適応，評価は高齢者機能評価(geriatric assessment:GA)を用いて判断されることが推奨されており，今後，OSを評価するだけでなく，生活の質や機能的状態など，高齢の癌患者にとって重要な指標を取り入れた，質の高い臨床試験の推進が望まれる．(著者抄録)
(キーワード): Cisplatin(治療的利用,毒性・副作用) *胃腫瘍(薬物療法) *抗腫瘍剤(治療的利用,毒性・副作用) 腫瘍再発 *食道腫瘍(薬物療法) *大腸腫瘍(薬物療法) 診療ガイドライン高齢者評価 Capecitabine(治療的利用) Oxaliplatin(治療的利用) Bevacizumab(治療的利用,毒性・副作用) Regorafenib(治療的利用) 免疫チェックポイント阻害剤(治療的利用) ヒト高齢者(65∼79)

佐藤康史, 高山哲治 :
化学療法術前化学療法治療反応性予測因子(V.胃癌の治療).,
日本臨牀, Vol.80, No.3, 281-287, 2022年3月. Yoshiro Niitsu, Yasushi Sato and Tetsuji Takayama :
Implications of glutathione-S transferase P1 in MAPK signaling as a CRAF chaperone: In memory of Dr. Irving Listowsky.,
Proceedings of the Japan Academy. Series B, Physical and biological sciences, Vol.98, No.2, 72-86, 2022.

(要約): Glutathione-S transferase P1 (GSTP1) is one of the glutathione-S transferase isozymes that belong to a family of phase II metabolic isozymes. The unique feature of GSTP1 compared with other GST isozymes is its relatively high expression in malignant tissues. Thus, clinically, GSTP1 serves as a tumor marker and as a refractory factor against certain types of anticancer drugs through its primary function as a detoxifying enzyme. Additionally, recent studies have identified a chaperone activity of GSTP1 involved in the regulation the function of various intracellular proteins, including factors of the growth signaling pathway. In this review, we will first describe the function of GSTP1 and then extend the details onto its role in the mitogen-activated protein kinase signal pathway, referring to the results of our recent study that proposed a novel autocrine signal loop formed by the CRAF/GSTP1 complex in mutated KRAS and BRAF cancers. Finally, the possibilities of new therapeutic approaches for these cancers by targeting this complex will be discussed.
(キーワード): Antineoplastic Agents / Cell Line, Tumor / Glutathione / Glutathione S-Transferase pi / Glutathione Transferase
(徳島大学機関リポジトリ): ● Metadata: 117383
(出版サイトへのリンク): ● Publication site (DOI): 10.2183/pjab.98.005
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 35153270; ● Search Scopus @ Elsevier (PMID): 35153270; ● Search Scopus @ Elsevier (DOI): 10.2183/pjab.98.005

(徳島大学機関リポジトリ: 117383, DOI: 10.2183/pjab.98.005, PubMed: 35153270) 佐藤康史, 宮本弘志, 佐川保, 高山哲治 :
COVID-19とがん治療,
腫瘍内科, Vol.27, No.4, 468-473, 2021年4月.

(キーワード): 患者管理院内感染(予防,合併症) 抗腫瘍剤(治療的利用) 疾病の発生死亡率 *腫瘍(薬物療法,合併症) 大腸腫瘍(薬物療法,合併症) 感染予防管理外来診療腫瘍医 *COVID-19(予防,合併症) ヒト
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1522543656005111296

(CiNii: 1522543656005111296) Takanori Kashihara, Naoki Muguruma, Shota Fujimoto, Yoshihiko Miyamoto, Yasushi Sato and Tetsuji Takayama :
Recent Advances in Molecular Imaging of Colorectal Tumors.,
Digestion, Vol.102, No.1, 57-64, Dec. 2020.

(要約): Recent endoscopic studies have revealed that small colorectal tumors are often overlooked during colonoscopy, indicating that more sensitive detection methods are needed. Molecular imaging has received considerable attention as a new endoscopic technique with high sensitivity. It generally employs a fluorescence-labeled compound that specifically binds to a molecule on the tumor. Fluorescent probes for molecular imaging are largely classified as 2 types: a fluorescence-labeled antibody targeting a molecule specifically expressed on the tumor cell surface such as epidermal growth factor receptor or vascular endothelial growth factor (VEGF); and a fluorescence-labeled small molecule compound targeting a molecule specifically expressed in tumor cells including c-Met, glutathione S-transferase, γ-glutamyltranspeptidase, cathepsin, or endothelin A receptor. These probes successfully detected colorectal tumors in several animal studies. Moreover, 3 recent human clinical trials evaluating endoscopic molecular imaging for colorectal tumors have been reported. In one study, a Cy5-labeled synthetic peptide against c-Met was developed, and fluorescent endoscopic observation with this probe detected a greater number of colorectal adenomas than with white light observation. Another trial used IR800-labeled anti-VEGF antibody, which sensitively detected human colorectal adenomas by fluorescent endoscopy. Last, a fluorescent probe with synthetic peptide against BRAF-positive cells was able to visualize sessile serrated lesions. The fluorescent probes accumulated at very high levels in colorectal tumor cells but at lower levels in surrounding nonneoplastic mucosa. Key Messages: We expect that molecular imaging techniques with fluorescent probes will soon lead to the establishment of a highly sensitive endoscopic method for colorectal tumor detection.
(出版サイトへのリンク): ● Publication site (DOI): 10.1159/000512168
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 33271567; ● Summary page in Scopus @ Elsevier: 2-s2.0-85097827136

(DOI: 10.1159/000512168, PubMed: 33271567, Elsevier: Scopus) 松本主之, 新井正美, 岩間達, 樫田博史, 工藤孝広, 小泉浩一, 佐藤康史, 関根茂樹, 田中信治, 田中屋宏爾, 田村和朗, 平田敬治, 深堀優, 江崎幹宏, 石川秀樹, 岩間毅夫, 岡崎康司, 斎藤豊, 松浦成昭, 武藤倫弘, 冨田尚裕, 秋山卓士, 山本敏樹, 石田秀行, 中山佳子 :
小児・成人のための若年性ポリポーシス症候群診療ガイドライン(2020年版),
遺伝性腫瘍, Vol.20, No.2, 79-92, 2020年9月.

(要約): 若年性ポリポーシス症候群は全消化管に過誤腫性ポリープである若年性ポリープが多発する,希少疾患である.SMAD4あるいはBMPR1A遺伝子の生殖細胞系列バリアントが原因として報告されている.約75
(キーワード): 消化管腫瘍(合併症,診断,外科的療法) *腫瘍症候群-遺伝性(遺伝学,診断,治療) 内視鏡法リスク Evidence-Based Medicine 診療ガイドライン Smad4 Protein *腸ポリポーシス(遺伝学,診断,治療) 骨形成因子受容体I型発癌 *若年性ポリポーシス(遺伝学,診断,治療) ヒト
(出版サイトへのリンク): ● Publication site (DOI): 10.18976/jsht.20.2_79
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1390285697599580160; ● Search Scopus @ Elsevier (DOI): 10.18976/jsht.20.2_79

(DOI: 10.18976/jsht.20.2_79, CiNii: 1390285697599580160) 三好人正, 佐藤康史, 六車直樹, 高山哲治 :
【消化器疾患のバイオマーカーの有用性と将来】食道癌の診断マーカーの将来,
消化器・肝臓内科, Vol.7, No.2, 105-110, 2020年2月.

(キーワード): Serpins 腫瘍抗原自己抗体 *腫瘍バイオマーカー(血液) *食道腫瘍(診断) 腺癌(診断) 変異扁平上皮癌(診断) 流血中腫瘍細胞 CA-19-9抗原 Keratin-19 循環腫瘍DNA(血液) 循環MicroRNA(血液) CYFRA21-1 p53抗体 SCC抗原ヒト

寺前智史, 田中久美子, 岡本耕一, 佐藤康史, 六車直樹, 高山哲治 :
【リンチ症候群と遺伝性消化管ポリポーシス】遺伝性消化管ポリポーシス Cowden症候群,
臨床消化器内科, Vol.34, No.6, 633-639, 2019年5月.

(要約): <文献概要>Cowden症候群は,皮膚・粘膜,消化管,乳腺,甲状腺など全身臓器に過誤腫性病変が多発する常染色体優性遺伝性疾患である.顔面小丘疹,口腔粘膜乳頭腫などの特徴的な皮膚病変を呈し,食道から直腸にいたる全消化管にポリポーシスを高率に合併する.食道に多発する白色扁平隆起は本症の特徴的な所見である.また乳癌などの悪性腫瘍を合併する例も多く,適切なサーベイランスが重要である.診断は,皮膚病変,悪性腫瘍,家族歴などを契機に行われる.有病率は20∼25万人に1人と推定されているが,見逃されている症例も少なくない.原因遺伝子の一つとしてPTEN遺伝子が同定されており,約80
(キーワード): 角化症(合併症) *過誤腫症候群-多発性(診断,病理学,合併症) 甲状腺腫瘍子宮内膜腫瘍集団サーベイランス変異消化器系内視鏡法乳頭腫乳房腫瘍腫瘍-第二原発遺伝学的検査丘疹(合併症) PTEN Phosphatase ヒト

田中育太, 友兼毅, 樫原孝典, 小田修治, 岡崎潤, 佐藤康史, 六車直樹 :
維持透析患者に対する胃瘻造設とその後の管理,
高松市民病院雑誌, Vol.33, 3-6, 2018年3月.

(キーワード): 胃鏡法 *胃造瘻術 *血液透析術後管理 *腎不全-慢性(治療,合併症) 腹膜透析(有害作用) 栄養管理ヒト

佐藤康史 :
【進行消化器癌のconversion surgery】腫瘍内科医の立場から,
外科, Vol.80, No.1, 7-13, 2018年1月.

(要約): 切除不能の進行癌症例に化学療法が奏効し治癒切除が可能と判断され,外科的治療が行われることをconversion surgeryと呼び,大腸癌肝転移例では良好な長期予後が報告されている.胃癌においてはコンセンサスは得られていないが,非治癒因子が切除可能となり,R0手術をめざせる症例では予後改善が期待されている.しかし,適切な対象症例の選択など多くの課題が残されており,治療開始時から腫瘍専門医と外科医が最大限の協力体制で取り組み,最適な切除のタイミングを図っていくことが必要である.今後,conversion surgeryに対するresectabilityの確立,有効な新規薬剤やレジメン開発により,多くの治癒症例が得られることが期待される.(著者抄録)
(キーワード): *胃腫瘍(外科的療法,薬物療法) 肝切除肝臓腫瘍(外科的療法,転移性) 抗腫瘍剤(治療的利用) *大腸腫瘍(外科的療法,薬物療法) アジュバント化学療法ネオアジュバント療法転移巣切除ヒト
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1522262180190743808

(CiNii: 1522262180190743808) 佐藤康史 :
生涯教育シリーズ消化器疾患診療の最前線胃癌薬物療法の今後の展開,
北海道医報臨時増刊号, No.1175, 10-13, 2017年2月. 佐藤康史 :
生涯教育シリーズ消化器疾患診療の最前線胃癌薬物療法の今後の展開,
北海道医報, No.1175, 10-13, 2016年8月.

(キーワード): *胃腫瘍(薬物療法,外科的療法) 抗腫瘍剤(治療的利用,毒性・副作用) 腫瘍多剤併用療法治療成績ランダム化比較試験医薬品開発腹腔内投与分子標的治療ヒト

佐藤康史, 大沼啓之, 加藤淳二 :
【Conversion Therapy(Adjuvant Surgery)-Stage IV症例に対する治療の奏効に伴う切除】各がん腫におけるConversion therapyとNeoadjuvant therapy 腫瘍内科医はConversion therapyをどう考えているのか?,
臨床腫瘍プラクティス, Vol.11, No.1, 21-26, 2015年2月.

(要約): <View Points!>Neoadjuvant chemotherapy(NAC)は根治切除が可能と判断した症例に対して術前に化学療法を行うことにより，腫瘍縮小や再発の一要因となるがんの微小転移のコントロールを目的とした治療．Conversion therapy(CT)は，当初根治切除不能もしくはborderlineであった転移巣を有する症例を対象とし，化学療法の奏効後に根治切除を行う治療として用いられる．NACとCTの決定的な差異は，治療前の状態が切除可能(NAC)か，切除不能(CT)かである．よってCTにおける切除適応には慎重な判断が要求され，この点でNACとは分けて扱うべきである．Stage IV症例に対する治療には限界があることから，今後，選択肢の中に唯一cureを望めるCTを加えることは無視できない．しかし確たるエビデンスがない領域であり，その適否の決定には，患者のQOLや希望を考慮した上での十分なディスカッションを経ることが必要．(著者抄録)
(キーワード): *胃腫瘍(予後,外科的療法,薬物療法) 胃切除抗腫瘍剤(治療的利用) 腫瘍多剤併用療法腫瘍転移 *大腸腫瘍(予後,外科的療法,薬物療法) *ネオアジュバント療法大腸切除ヒト

佐藤康史, 加藤淳二 :
【抗がん剤の副作用と支持療法-より適切な抗がん剤の安全使用をめざして-】臓器別副作用と対策消化器系肝機能障害,
日本臨牀, Vol.73, 369-374, 2015年2月.

(キーワード): Cisplatin(治療的利用,毒性・副作用,薬理学) *化学物質誘発肝障害(診断) *抗腫瘍剤(治療的利用,毒性・副作用,薬理学) 抗腫瘍性抗生物質(治療的利用,毒性・副作用,薬理学) *腫瘍(薬物療法) 抗腫瘍性代謝拮抗物質(治療的利用,毒性・副作用,薬理学) 薬物用量反応関係アルキル化抗腫瘍剤(治療的利用,毒性・副作用,薬理学) Erlotinib(治療的利用,毒性・副作用,薬理学) Imatinib(治療的利用,毒性・副作用,薬理学) Tubulin Modulators(治療的利用,毒性・副作用,薬理学) 分子標的治療(有害作用) Topoisomerase Inhibitors(治療的利用,毒性・副作用,薬理学) ヒト

佐藤康史, Junji Kato :
[Hepatotoxicity of chemotherapy].,
日本臨牀, Vol.73 Suppl 2, 369-374, 2015年2月.

(キーワード): Antineoplastic Agents / Chemical and Drug Induced Liver Injury / Humans / Neoplasms
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25831785; ● Search Scopus @ Elsevier (PMID): 25831785

(PubMed: 25831785) 佐藤康史, 大沼啓之, 加藤淳二 :
腫瘍内科医はConversion therapyをどう考えているのか? (特集 Conversion Therapy (Adjuvant Surgery) : Stage Ⅳ症例に対する治療の奏効に伴う切除) -- (各がん腫におけるConversion therapyとNeoadjuvant therapy),
臨床腫瘍プラクティス, Vol.11, No.1, 21-26, 2015年.

(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1522825130972467712

(CiNii: 1522825130972467712) 佐藤康史, 平川昌宏, 大沼啓之, 加藤淳二 :
【最新胃癌学-基礎と臨床の最新研究動向-】胃癌の治療戦略化学療法術前化学療法治療反応性予測因子,
日本臨牀, Vol.72, 459-463, 2014年1月.

(キーワード): *Cisplatin(治療的利用) DNA-Binding Proteins DNA修復 Endonucleases *胃腫瘍(薬物療法) 腫瘍多剤併用療法第II相試験治療成績 *抗腫瘍剤耐性 *ネオアジュバント療法 *Docetaxel(治療的利用) *TS-1(治療的利用) ERCC1 Protein DDB2 Protein *DCS Protocol ヒト

佐藤康史, 平川昌宏, 大沼啓之, 加藤淳二 :
【最新胃癌学-基礎と臨床の最新研究動向-】胃癌の治療戦略化学療法術前化学療法治療反応性予測因子,
日本臨牀, Vol.72, 459-463, 2014年1月.

(キーワード): *Cisplatin(治療的利用) DNA-Binding Proteins DNA修復 Endonucleases *胃腫瘍(薬物療法) 腫瘍多剤併用療法第II相試験治療成績 *抗腫瘍剤耐性 *ネオアジュバント療法 *Docetaxel(治療的利用) *TS-1(治療的利用) ERCC1 Protein DDB2 Protein *DCS Protocol ヒト

勝木伸一, 藤田朋紀, 小松悠弥, 北岡慶介, 高梨訓博, 和賀永里子, 太田英敏, 佐藤康史, 加藤淳二 :
【抗血栓薬/NSAIDsと消化管障害-その実態と最新のマネージメントに迫る-】抗血栓薬/NSAIDsによる消化管障害とそのマネージメント抗潰瘍薬による薬剤性小腸障害の予防・治療の実際,
消化器の臨床, Vol.16, No.2, 191-193, 2013年4月.

(要約): 薬剤性小腸障害を認めた場合，まずはじめに，原因薬剤の投与を中止もしくは変更可能か否か検討することが必要である．PPIは薬剤性小腸潰瘍を悪化させる可能性があり，注意が必要である．Histamine H2 receptor antagonistのなかには，小腸粘膜障害を軽減させる作用を持つ薬剤もある．PG製剤(ミソプロストール)は有効であるが，副作用も多い．レバミピドは内因性PG増加作用，free radical除去作用があり，効果が期待できる．(著者抄録)
(キーワード): *消化性潰瘍治療剤(治療的利用,毒性・副作用) 多剤併用療法 Misoprostol(治療的利用) Rebamipide(治療的利用) Teprenone(治療的利用) Proton Pump Inhibitors(治療的利用,毒性・副作用) *小腸疾患(化学的誘発,予防) *小腸潰瘍(化学的誘発,予防) ヒト

勝木伸一, 藤田朋紀, 北岡慶介, 高梨訓博, 和賀永里子, 小松悠弥, 太田英敏, 佐藤康史, 加藤淳二 :
【必修!大腸ESD】大腸の特性からみたESDに適したスコープや処置具の選択,
消化器内視鏡, Vol.25, No.3, 421-425, 2013年3月.

(要約): 大腸は長く，複雑で個人差がある．時には癒着も存在し，病変に到達することすら難しいといった症例もある．したがって，大腸ESDを安全かつ確実に行うためには，スコープや処置具に関する知識や理解が必要となる．ウォータージェット機能を有するスコープが開発されているが，その剛性や視野の違いについてよく知っておく必要がある．また，バルーン内視鏡は，ESD難航例に有効である．大腸は壁が薄く，穿孔の危険があるため，高周波出力設定は，胃に用いる設定よりも低く抑える必要がある．(著者抄録)
(キーワード): 外科用器具 *大腸内視鏡法外科的止血 *大腸腫瘍(外科的療法) 大腸内視鏡 *内視鏡的粘膜下層剥離術硬性鏡撮像視野ヒト

佐藤康史, 大沼啓之, 加藤淳二 :
【消化器がん化学療法レジメン】胃がん胃がん化学療法に用いられるレジメンティーエスワン(S-1)+シスプラチン(CDDP)療法,
臨床腫瘍プラクティス, 40-41, 2012年9月.

(キーワード): *Cisplatin(毒性・副作用,治療的利用) *胃腫瘍(薬物療法) 悪心(化学的誘発) 腫瘍多剤併用療法(有害作用) 好中球減少症(化学的誘発) *投薬計画白血球減少症(化学的誘発) 臨床試験治療成績 *TS-1(毒性・副作用,治療的利用) ヒト

佐藤康史, 大沼啓之, 加藤淳二 :
【消化器がん化学療法レジメン】胃がん胃がん化学療法に用いられるレジメンティーエスワン(S-1)+シスプラチン(CDDP)+ドセタキセル(DOC)【DCS療法】,
臨床腫瘍プラクティス, 42-43, 2012年9月.

(キーワード): *Cisplatin(毒性・副作用,治療的利用) *胃腫瘍(薬物療法) 嘔吐(化学的誘発) 悪心(化学的誘発) 下痢(化学的誘発) 腫瘍多剤併用療法(有害作用) 好中球減少症(化学的誘発) *投薬計画白血球減少症(化学的誘発) 治療成績 *Docetaxel(毒性・副作用,治療的利用) *TS-1(毒性・副作用,治療的利用) ヒト

(キーワード): *Cisplatin(毒性・副作用,治療的利用) *胃腫瘍(薬物療法) 嘔吐(化学的誘発) 悪心(化学的誘発) 下痢(化学的誘発) 腫瘍多剤併用療法(有害作用) 好中球減少症(化学的誘発) *投薬計画白血球減少症(化学的誘発) 治療成績 *Docetaxel(毒性・副作用,治療的利用) *TS-1(毒性・副作用,治療的利用) ヒト

佐藤康史, 大沼啓之, 加藤淳二 :
【消化器がん化学療法レジメン】胃がん胃がん化学療法に用いられるレジメンイリノテカン(CPT-11)+シスプラチン(CDDP)療法,
臨床腫瘍プラクティス, 44-45, 2012年9月.

(キーワード): *Cisplatin(毒性・副作用,治療的利用) *胃腫瘍(薬物療法) 悪心(化学的誘発) 下痢(化学的誘発) 腫瘍多剤併用療法(有害作用) 好中球減少症(化学的誘発) 食欲不振(化学的誘発) *投薬計画臨床試験治療成績 *Irinotecan(毒性・副作用,治療的利用) ヒト

伊東竜哉, 沖田憲司, 西舘敏彦, 古畑智久, 山下健太郎, 篠村恭久, 佐藤康史, 加藤淳二, 平田公一 :
【消化器癌に対するneo-adjuvant therapyの最新情報】局所進行大腸癌のdown stagingを目的としたneo-adjuvant therapy,
外科, Vol.74, No.9, 932-936, 2012年9月.

(要約): 局所進行大腸癌の外科治療においては，たとえ遠隔転移を伴わなくとも，外科的切除縁の確保の課題や拡大切除の侵襲程度によっては，切除不能と判断せざるをえないことも多い．近年，化学療法や放射線療法の進歩により，切除不能大腸癌に対しdown stagingをめざしたneo-adjuvant therapyを行い切除が可能となる，いわゆるconversion例が多く報告されている．局所進行癌に対するconversion therapyについての詳細な検討ないものの，FOLFOXやFOLFIRIに分子標的治療薬を併用したレジメンおよび放射線療法との組み合わせの効果が，治癒切除率の向上と生命予後の延長という点で有望視されている．(著者抄録)
(キーワード): Camptothecin(類似体・誘導体) Fluorouracil(治療的利用) Leucovorin 血栓症(化学的誘発) 腫瘍多剤併用療法出血(化学的誘発) *大腸腫瘍(薬物療法,外科的療法,放射線療法) 直腸腫瘍(薬物療法,外科的療法,放射線療法) 有機白金化合物治療成績 *ネオアジュバント療法 Cetuximab(治療的利用) Bevacizumab(治療的利用,毒性・副作用) Levofolinate Calcium(治療的利用) *放射線化学療法 *分子標的治療 IFL Protocol FOLFOX Protocol ヒト

勝木伸一, 藤田朋紀, 高梨訓博, 和賀永里子, 下立雄一, 太田英敏, 倉敏郎, 佐藤康史, 加藤淳二 :
消化管の新たな映像(第6回) カプセル内視鏡,
Frontiers in Gastroenterology, Vol.17, No.3, 240-243, 2012年7月.

(キーワード): *カプセル内視鏡法カプセル内視鏡ヒト

新津洋司郎, 尾留川直子, 佐藤康史 :
【分子・細胞から解明する肝臓のバイオロジー】肝星細胞を標的とした肝硬変の治療戦略,
実験医学, Vol.29, No.13, 2114-2122, 2011年8月.

(要約): 肝星細胞は，肝が傷害されると増殖し，コラーゲンを生産することから，肝硬変の責任細胞と考えられている．ここ数年同細胞の機能あるいは増殖(生存)を阻害する肝硬変の治療戦略が報告されるようになった．しかし，それらの多くは標的分子特異性あるいは星細胞特異性という点で問題があり臨床応用に至っていない．われわれは，星細胞がVA(ビタミンA)を取り込むという事実に着目し，VAを表出しているリポソームを作成したうえでコラーゲンの特異的シャペロンタンパク質に対するsiRNAをそのなかに含有させた薬剤を開発した．この薬剤は全身投与によりラットの肝硬変モデルにおいてきわめて高い有効性を示した．その治療効果には星細胞からのコラーゲン分泌抑制以外に同細胞がアポトーシスに陥るというメカニズムが関与していた．(著者抄録)
(キーワード): Collagen リポソーム Vitamin A *肝硬変(薬物療法) 肝再生漢方薬(治療的利用) 細胞外基質疾患モデル(動物) アポトーシスノックアウトマウス Matrix Metalloproteinases Tissue Inhibitor of Metalloproteinase-1 Tissue Inhibitor of Metalloproteinase-2 *伊東細胞医薬品開発 siRNA *分子標的治療ヒトマウスラット動物

信岡隆幸, 原田敬介, 及能大輔, 三浦亮, 木村康利, 水口徹, 佐藤康史, 加藤淳二, 平田公一 :
【StageIV胃癌治療への挑戦】StageIV胃癌に対する積極的化学療法後の胃切除の安全性,
消化器外科, Vol.34, No.5, 559-567, 2011年5月.

(キーワード): Cisplatin(治療的利用,毒性・副作用) *胃腫瘍(薬物療法,外科的療法) *胃切除開腹術腫瘍多剤併用療法術後管理術前管理大学病院リンパ節切除治療成績 Docetaxel(治療的利用,毒性・副作用) TS-1(治療的利用,毒性・副作用) 栄養管理ヒト

宮本弘志, 三好人正, 竹中英喬, 木村哲夫, 竹内尚, 岡久稔也, 佐藤康史, 加藤淳二, 高山哲治 :
【StageIV胃癌治療への挑戦】StageIV胃癌に対するDCS療法の意義,
消化器外科, Vol.34, No.5, 575-581, 2011年5月.

(キーワード): *Cisplatin(治療的利用,毒性・副作用) *胃腫瘍(薬物療法) 腫瘍多剤併用療法生存分析第I相試験第II相試験治療成績 *Docetaxel(治療的利用,毒性・副作用) *TS-1(治療的利用,毒性・副作用) ヒト

佐藤康史, 高山哲治, 加藤淳二 :
【胃癌化学療法】進行再発胃癌に対する術前療法としてのDCS療法,
消化器内科, Vol.52, No.1, 44-47, 2011年1月.

(キーワード): *Cisplatin(治療的利用) *胃腫瘍(薬物療法,予後) 腫瘍多剤併用療法腫瘍再発生存率治療成績 *ネオアジュバント療法 *Docetaxel(治療的利用) *TS-1(治療的利用) ヒト

佐藤康史, 村瀬和幸, 新津洋司郎, 加藤淳二 :
ビタミンA-リポソームsiRNA HSP47を用いた肝硬変の治療,
最新医学, Vol.65, No.12, 2593-2598, 2010年12月.

(キーワード): Collagen Hydroxyproline *リポソーム Retinol-Binding Proteins *Vitamin A *肝硬変(実験的,治療) 疾患モデル(動物) アポトーシス伊東細胞肝線維症(実験的,治療) *siRNA *HSP47 Heat-Shock Proteins 静脈内注射ヒトマウスラット動物

勝木伸一, 下立雄一, 高梨訓博, 和賀永里子, 藤田朋紀, 大野敬祐, 佐々木寿誉, 染谷哲史, 佐々木一晃, 高田義人, 千葉大樹, 大沼啓之, 佐川保, 佐藤康史, 加藤淳二, 藤田昌宏 :
【ESDのさらなる普及に向けて】ESD困難例への対処大腸Endoscopic Submucosal Dissection(ESD)困難例に対するダブルバルーン式内視鏡の有用性安全で確実なESDを行うために,
消化器医学, Vol.8, 26-33, 2010年10月.

(キーワード): 腺癌(外科的療法,病理学) *大腸腫瘍(外科的療法,病理学) *内視鏡的粘膜下層剥離術 *ダブルバルーン小腸内視鏡法ヒト中年(45∼64) 高齢者(65∼79) 高齢者(80∼) 男女

佐藤康史, 加藤淳二 :
がん治療の新たな展開分子標的療法抗VEGF抗体や抗EGFR抗体などの抗体療法,
北海道医報, No.1099, 26-29, 2010年4月.

(キーワード): 腫瘍バイオマーカー *大腸腫瘍(薬物療法) ras癌原遺伝子タンパク質p21 治療成績 *Cetuximab(薬理学,治療的利用) *Bevacizumab(薬理学,治療的利用) Vascular Endothelial Growth Factor A(薬理学) *分子標的治療 ErbB Receptors(薬理学) KRAS Protein ヒト

佐藤康史, 村瀬和幸, 新津洋司郎, 加藤淳二 :
【消化器疾患におけるRNA医学の進展を探る】siRNAは消化器疾患治療にどのように応用されるのか,
分子消化器病, Vol.7, No.1, 39-43, 2010年3月.

(要約): 近年，種々の難治性疾患に対してsmall interfering RNA(siRNA)を用いたRNA干渉(RNA interference:RNAi)を利用した新規治療薬の開発が期待されている．われわれは，肝線維化の終末像である肝硬変の治療を目的に，コラーゲンの分子シャペロンheat shock protein 47(HSP47)に対するsiRNAを作製し，コラーゲン産生をおこなう肝星細胞(hepatic stellate cell:HSC)に送達することで，コラーゲン産生を特異的に抑制することを試みた．この方法はラット肝線維症モデルで著明な効果を示したことから，ヒト肝硬変を回復させる治療法となる可能性が示唆された．(著者抄録)
(キーワード): Collagen 遺伝子導入 *肝硬変(薬物療法) 疾患モデル(動物) 分子シャペロン伊東細胞医薬品開発 RNA干渉 *siRNA(治療的利用) HSP47 Heat-Shock Proteins 分子標的治療ヒトラット動物

勝木伸一, 藤田朋紀, 和賀永里子, 安部智之, 大沼啓之, 千葉大樹, 佐川保, 佐藤康史, 加藤淳二 :
【小腸疾患に対する最新のアプローチ】Virtual endoscopyの小腸疾患への応用,
Intestine, Vol.13, No.5, 552-555, 2009年9月.

(キーワード): *消化管内視鏡法三次元イメージング *小腸疾患(診断,X線診断) *マルチスライスCT MPR (Multiplanar Reconstruction) *小腸内視鏡法ヒト

村瀬和幸, 佐藤康史, 加藤淳二, 新津洋司郎 :
【siRNA創薬新しい創薬】肝硬変に対するsiRNAを用いた新規治療,
BIO Clinica, Vol.24, No.1, 50-54, 2009年1月.

(要約): 肝硬変に対する有効な治療法はいまだ確立していない．そこで我々は肝硬変の原因となるコラーゲンの過剰産生を抑制する目的で，コラーゲン合成に必須である分子シャペロンHSP47に対するsiRNAを作成した．さらにビタミンAの取り込み・貯蔵を行う肝星細胞の役割を利用し，ビタミンA結合型リポソームを用い，siRNAを肝星細胞に送達する事でコラーゲン産生を特異的に抑制する方法を開発した．この方法はラットの肝線維症モデルで顕著な線維化改善効果を示した事から，ヒト肝硬変を快復させる治療法となる可能性が示唆された．(著者抄録)
(キーワード): リポソーム Retinol-Binding Proteins *肝硬変(病理学,薬物療法,実験的) ドラッグデリバリーシステム伊東細胞 *siRNA(薬理学,治療的利用) HSP47 Heat-Shock Proteins ラット動物

佐藤康史, 加藤淳二, 村瀬和幸, 新津洋司郎 :
【肝の線維化を探る】線維化の制御と治療の可能性コラーゲン生成抑制による線維化治療の可能性,
肝·胆·膵, Vol.57, No.2, 299-304, 2008年8月.

(キーワード): *Collagen(薬理学) Vitamin A 肝硬変(実験的) 疾患モデル(動物) アポトーシス伊東細胞 *肝線維症(病因) siRNA HSP47 Heat-Shock Proteins ヒトラット動物

佐藤康史, 村瀬和幸, 加藤淳二, 新津洋司郎 :
コラーゲン特異的シャペロンに対する siRNA を送達するビタミン A 結合リポソームによる肝硬変の治療,
実験医学, No.26, 2105-2108, 2008年. 阿部清一郎, 高山哲治, 佐川保, 佐藤康史, 新津洋司郎 :
【早期大腸癌の取り扱い】大腸ポリープの取り扱いどのようなポリープを取るか，取った後どうするか,
消化器の臨床, Vol.10, No.1, 45-49, 2007年2月.

(要約): 大腸ポリープの大部分を占める腺腫は前癌病変であることから，基本的に内視鏡的切除の適応である．ただし，腫瘍径5mm未満の微小ポリープについては必ずしも切除する必要はないと思われる．また，大腸ポリープ切除後のサーベイランスについては米国でガイドラインが発表されており，腺腫の個数，サイズ，組織学的悪性度に応じたサーベイランス期間が示されている．わが国においてもポリープ切除後の適切なサーベイランス期間を調べるためにJapan Polyp Study Workgroupによるrandomized control trialが開始され，その結果が待たれる．(著者抄録)
(キーワード): *大腸ポリープ(外科的療法) 集団サーベイランス臨床試験内視鏡的粘膜切除術ヒト

佐藤康史, 佐川保, 高山哲治, 新津洋司郎 :
【食道・胃・十二指腸疾患】治療食道癌・胃癌の外来化学療法外来化学療法施設が普及した今日的指針,
Medical Practice, Vol.23, No.8, 1409-1414, 2006年8月.

(キーワード): Fluorouracil(治療的利用,毒性・副作用) *胃腫瘍(薬物療法) 嘔吐(化学的誘発) 悪心(化学的誘発) 下痢(化学的誘発) *食道腫瘍(薬物療法) Irinotecan(治療的利用,毒性・副作用) TS-1(治療的利用,毒性・副作用) 外来診療ヒト

高山哲治, 佐藤康史, 新津洋司郎 :
大腸癌対策最前線大腸発癌メカニズムの最前線,
Frontiers in Gastroenterology, Vol.11, No.3, 230-235, 2006年7月.

(キーワード): 前癌状態染色体 *大腸腫瘍(病因,遺伝学) 腫瘍過程分子生物学メチル化マイクロサテライトリピートプロモーター領域エピジェネティックプロセス染色体不安定性異常腺窩巣ヒト

高山哲治, 加藤淳二, 佐藤康史, 新津洋司郎 :
【消化器炎症発癌の分子機構を探る】消化器発癌に対するchemopreventionを考える,
分子消化器病, Vol.2, No.2, 138-144, 2005年6月.

(キーワード): Ciclosporin(治療的利用) Interferons(治療的利用) Prednisolone(治療的利用) 肝細胞癌(予防) *消化器腫瘍(悪性,予防,合併症) 大腸炎-潰瘍性(合併症,薬物療法) 腫瘍過程(予防) Lamivudine(治療的利用) *化学予防 Mesalazine(治療的利用) ヒト

高橋稔, 佐藤康史, 佐藤勉, 井山諭, 住吉徹哉, 山田康之, 深浦純生, 奥隆臣, 高橋祥, 町田卓郎, 佐川保, 新津洋司郎 :
【膵癌の研究・診療における新たな展開ゲノム医学の導入】膵癌遺伝子治療の可能性をさぐる,
胆と膵, Vol.24, No.5, 363-370, 2003年5月.

(要約): 手術不能進行膵癌は,既存の治療に抵抗性であり生命予後の最も悪い悪性腫瘍の1つである.この克服を目的に既に欧米を中心に膵癌に対する遺伝子治療の臨床試験が行われている.癌の遺伝子治療は直接細胞傷害活性をもたらすものと間接的に抗腫瘍効果をもたらすものとに大きく分類される.現在のところ前者では腫瘍特異的に増殖可能な各種ウイルスを用いた治療法が,また後者としては抗血管新生遺伝子治療が,或いはこれらを併用した新たな治療法が期待されている.膵癌に対する遺伝子治療が有効な治療法となるためには既存の治療法を上回る成績を得ることが必要であり,まず適切な臨床試験を行うことが肝要である
(キーワード): ヒトアデノウイルスポリオウイルス遺伝子ベクター *遺伝学的治療血管形成タンパク質病的血管新生 *膵臓腫瘍(治療) シンプレックスウイルス属ワクシニアウイルスヒト

宮西浩嗣, 高山哲治, 中島隆晴, 信岡純, 林毅, 茎津武大, 安部智之, 高梨訓博, 佐藤康史, 石渡裕俊, 新津洋司郎 :
【消化器癌化学療法の新たな展開】GST-π分子を標的とした新しい消化器癌の治療,
消化器科, Vol.36, No.4, 408-412, 2003年4月.

(キーワード): Cisplatin(治療的利用) Doxorubicin(治療的利用) Etoposide(治療的利用) Fluorouracil(治療的利用) Melphalan(治療的利用) Vincristine(治療的利用) *消化器腫瘍(悪性,薬物療法) 抗腫瘍剤効力検定 Glutathione S-transferase T1 ヒト

佐藤康史, 深浦純生, 佐藤勉, 高橋稔, 新津洋司郎 :
【胃癌の治療進行・再発胃癌の治療新しい機序による治療】遺伝子治療,
日本臨牀, Vol.59, 443-448, 2001年4月.

(キーワード): 胃腫瘍(悪性,治療) 遺伝子ベクター遺伝学的治療再発治療ヒト

高橋稔, 佐川保, 佐藤勉, 佐藤康史, 井山諭, 奥隆臣, 住吉徹哉, 深浦純生, 山田康之, 新津洋司郎 :
【消化器疾患の遺伝子治療】進行消化器癌に対するアデノウイルスベクターによる遺伝子治療,
G.I.Research, Vol.8, No.6, 435-446, 2000年12月.

(要約): 癌に対するアデノウイルスベクター(AdV)を用いた遺伝子治療は大きくわけて,従来より広く用いられている複製不能AdVによるものと,最近になり報告されている複製可能AdVによるものとにわけることができる.複製不能AdVを用いた癌に対する遺伝子治療の戦略は更に自殺遺伝子治療,免疫遺伝子治療,癌遺伝子・癌抑制遺伝子を標的とした遺伝子治療,抗癌剤耐性遺伝子導入による骨髄幹細胞保護,転移抑制遺伝子治療,血管新生抑制遺伝子治療に分類される.進行消化器癌に対する遺伝子治療の臨床応用はその緒についたばかりであり,今後の発展が期待される
(キーワード): アデノウイルス科遺伝子ベクター遺伝学的治療癌抑制遺伝子消化器腫瘍(悪性,治療) 癌遺伝子トランスジェニック自殺遺伝子

新津洋司郎, 高橋稔, 佐藤康史 :
各科における先端医療癌に対する遺伝子治療,
北海道医学雑誌, Vol.75, No.4, 229-235, 2000年7月.

(キーワード): 遺伝子ベクター遺伝学的治療癌抑制遺伝子腫瘍(悪性,治療) トランスジェニック自殺遺伝子ヒト

Y Niitsu, M Takahashi, 佐藤康史 :
[Gene therapy for cancer].,
北海道医学雑誌, Vol.75, No.4, 229-235, 2000年7月.

(キーワード): Animals / Genetic Therapy / Genetic Vectors / Humans / Neoplasms
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 10976402; ● Search Scopus @ Elsevier (PMID): 10976402

(PubMed: 10976402) 新津洋司郎, 高橋稔, 佐藤康史 :
【癌治療とDDS】癌の遺伝子治療におけるDDS,
Drug Delivery System, Vol.15, No.1, 32-38, 2000年1月.

(キーワード): リポソームプラスミド遺伝子ベクター遺伝学的治療腫瘍治療ドラッグデリバリーシステムリガンド遺伝子銃ミサイル療法ヒト

渡辺直樹, 佐藤康史, 新津洋司郎 :
遺伝子治療の最前線 TNF遺伝子導入による癌治療,
臨床外科, Vol.53, No.4, 469-474, 1998年4月.

(キーワード): 腫瘍壊死因子遺伝子導入遺伝学的治療腫瘍(悪性,治療) 治療

渡辺直樹, 佐藤康史, 山内尚文 :
【Drug Delivery Systemの進歩最適薬物治療システムを目指す生体内薬物送達技術の最近の動向】細胞内遺伝子導入法トランスフェリン受容体を介した癌細胞への遺伝子導入法,
日本臨牀, Vol.56, No.3, 724-730, 1998年3月.

(キーワード): Transferrin 遺伝子導入薬物細胞腫瘍 Transferrin Receptors ドラッグデリバリーシステム薬物療法

(キーワード): Transferrin 遺伝子導入薬物細胞腫瘍 Transferrin Receptors ドラッグデリバリーシステム薬物療法

N Watanabe, 佐藤康史, N Yamauchi, Y Niitsu :
[Gene delivery into human cancer cells via transferrin receptor].,
日本臨牀, Vol.56, No.3, 724-730, 1998年3月.

(要約): At present, vectors widely used for gene transduction are retroviruses and adenoviruses. However, the transduction using these vectors are primarily conducted ex vivo. The direct in vivo gene delivery method to target tumor cells are required. Trials to augment specificity of gene targeting to tumor cells have been in progress including approaches to use modified virus particles by gene technology instead of wild type particles or to take advantage of ligand-receptor or antibody-antigen systems by allowing vector DNAs to bind these ligand and antibodies. Transferrin receptor (TfR) is widely distributed on actively proliferating cells and is therefore an appropriate target for in vivo gene delivery into those cells. We developed a simple method to conjugate biotinylated double-stranded DNA to biotinylated Tf via streptavidin and demonstrated successful transduction of the conjugate into TfR-positive human cancer cells. The present method may provide a novel technique for gene transduction, which may be used especially to transfer various DNA vectors into cells specifically expressing TfR, in vivo as well as in vitro.
(キーワード): Adenoviridae / Biotin / DNA / Drug Delivery Systems / Genetic Therapy / Genetic Vectors / Glycerol / Humans / Liposomes / Neoplasms / Polylysine / Receptors, Transferrin
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 9549364; ● Search Scopus @ Elsevier (PMID): 9549364

(PubMed: 9549364) 越田吉一, 佐藤康史, 高橋稔 :
腫瘍免疫遺伝子導入癌細胞ワクチン,
Mebio, Vol.13, No.11, 92-101, 1996年11月.

(キーワード): ワクチン遺伝子導入腫瘍(悪性,免疫療法) 能動免疫療法

越田吉一, 佐藤康史, 高橋稔 :
腫瘍免疫遺伝子導入癌細胞ワクチン,
Mebio, Vol.13, No.11, 92-101, 1996年11月.

(キーワード): ワクチン遺伝子導入腫瘍(悪性,免疫療法) 能動免疫療法

佐藤康史, 新津洋司郎 :
日本における遺伝子治療の基礎実験の現状 TNFを用いた癌遺伝子治療,
蛋白質・核酸・酵素, Vol.40, No.17, 2694-2699, 1995年12月.

(キーワード): 腫瘍壊死因子(治療的利用) 遺伝学的治療腫瘍(悪性,治療) 治療

佐藤康史, 新津洋司郎 :
日本における遺伝子治療の基礎実験の現状 TNFを用いた癌遺伝子治療,
蛋白質・核酸・酵素, Vol.40, No.17, 2694-2699, 1995年12月.

(キーワード): 腫瘍壊死因子(治療的利用) 遺伝学的治療腫瘍(悪性,治療) 治療

佐藤康史, Y Niitsu :
[Gene therapy of cancer using TNF gene].,
蛋白質核酸酵素, Vol.40, No.17, 2694-2699, 1995年12月.

(キーワード): Animals / Gene Transfer Techniques / Humans / Immunotherapy, Active / Immunotherapy, Adoptive / Neoplasms / Tumor Necrosis Factor-alpha
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 8584723; ● Search Scopus @ Elsevier (PMID): 8584723

(PubMed: 8584723)

講演・発表

Yutaka Kawano, Maki Tanaka, Yasushi Sato, Tetsu Tomonari, Hironori Tanaka, Takeshi Mitsuhashi and Tetsuji Takayama :
Activation of HNF4α pathway by treatment with botanical plant, Acanthopanax Senticosus, ameliorates steatohepatitis in high-fat fed mice model.,
AASLD2023, Boston, Nov. 2023. Yoshifumi Kida, Toshiya Okahisa, Yasushi Sato, Masahiro Bando, shota fujimoto, Tadahiko Nakagawa, Tomoyuki Kawaguchi, Fumika Nakamura, Koichi Okamoto, Hiroshi Miyamoto, Masahiro Sogabe, Koichi Tsuneyama and Tetsuji Takayama :
Thepapeutic strategy of Ulcerative Colitis targeting Urokinase-type Plasminogen Activator.,
DDW2023, May 2023. Tomoyuki Kawaguchi, Koichi Okamoto, shota fujimoto, Masahiro Bando, hironori wada, Hiroshi Miyamoto, Yasushi Sato, Naoki Muguruma and Tetsuji Takayama :
Lansoprazole as an effective chemopreventive agent for serrated-neoplasia pathway; A comprehensive analysis using connectivity map.,
DDW2023, May 2023. Yasushi Sato, Kazuyoshi Noda, Yasuyuki Okada, Kensei Nishida, Yutaka Kawano, Toshihito Tanahashi, Masanori Takehara, Yasuteru Fujino, Koichi Okamoto, Hiroshi Miyamoto and Tetsuji Takayama :
Exosomal miR-199a-3p secreted from cancer-associated adipocytes promote pancreatic cancer progression.,
DDW2023, Chicago, May 2023. Yutaka Kawano, Maki Tanaka, Yasushi Sato, Tetsu Tomonari, Hironori Tanaka, Takeshi Mitsuhashi and Tetsuji Takayama :
Activation of HNF4α pathway by treatment with botanical plant, Acanthopanax senticosus, ameliorates steatohepatitis in high-fat fed mice model.,
DDW2023, Chicago, May 2023. Tetsuji Takayama, Yoshifumi Kida, Toshiya Okahisa, Yasushi Sato, Masahiro Bando, shota Fujimoto, Tomoyuki Kawaguchi, Fumika Nakamura, Koichi Okamoto, Hiroshi Miyamoto, Koichi Tsuneyama and Masahiro Sogabe :
The relevance of urokinase-type plasminogen activator in pathogenesis of ulcerative colitis.,
WCOG2022 (World Congress of Gastroenterology), Dubai, Dec. 2022. Hiroyuki Ueda, Yasuhiro Mitsui, Makoto Takishita, Mitsuyasu Yano, Masanori Takehara, Akira Fukuya, Tomoyuki Kawaguchi, Kazuyoshi Noda, Shinji Kitamura, Koichi Okamoto, Yasushi Sato, Naoki Muguruma and Tetsuji Takayama :
Clinicopathologial Analysis of Six Families with Gastric Adenocarcinoma and Proximal Polyposis of the stomach (GAPPS).,
DDW2020, May 2020. Yasushi Sato, Kumiko Tanaka, Ishikawa Hideki, Satoshi Teramae, Fumika Nakamura, Yasuhiro Mitsui, Kagemoto Kaizo, Hiroshi Miyamoto, Koichi Okamoto, Naoki Muguruma, Ohmiya Naoki, Mutoh Michihiro and Tetsuji Takayama :
Small- intestinal involvement in familial adenomatous polyposis: characteristics and genotype- phenotype correlation from a Japanese cohort study,
DDW, May 2020. Yasushi Sato, Tetsu Tomonari, Hironori Tanaka, Takahiro Tanaka, Hirao Akihiro, Koichi Okamoto, Hiroshi Miyamoto, Naoki Muguruma, Kagiwada Harumi, Kitazawa Masashi, Fukui Kazuhiko, Horimoto Katsuhisa and Tetsuji Takayama :
Potential use of lenvatinib for patients with unresectable hepatocellular carcinoma beyond progression of sorafenib treatment: A real-world evidence and in vitro assessment with protein phosphorylation array,
ASCO Gastrointestinal Cancers Symposium(ASCO-GI 2020), San Francisco, Jan. 2020.

(出版サイトへのリンク): ● Publication site (DOI): 10.1200/JCO.2020.38.4_suppl.485
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1200/JCO.2020.38.4_suppl.485

(DOI: 10.1200/JCO.2020.38.4_suppl.485) Ohnuma Hiroyuki, Yasushi Sato, Omori Ginji, Onoyama Naoki, Ameda Saki, Ito Ryo, Hamaguchi Kota, Hayasaka Naotaka, Sato Masanori, Murase Kazuyuki, Takada Kohichi, Miyanishi Koji, Ito Tatsuya, Nobuoka Takayuki, Takemasa Ichiro and Kato Junji :
Survival benefit of conversion therapy after intensive chemotherapy for unresectable metastatic gastric cancer: A propensity score-matched analysis.,
ASCO Gastrointestinal Cancers Symposium(ASCO-GI 2020), San Francisco, Jan. 2020.

(出版サイトへのリンク): ● Publication site (DOI): 10.1200/JCO.2020.38.4_suppl.354
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1200/JCO.2020.38.4_suppl.354

(DOI: 10.1200/JCO.2020.38.4_suppl.354) Sagawa Tamotsu, Yasushi Sato, Hamaguchi Kyoko, Hirakawa Masahiro, Nagashima Hiroyuki, Waga Eriko, Fujikawa Koshi and Takahashi Yasuo :
Improved efficacy to cytotoxic agents chemotherapy after immune checkpoint inhibitors exposure in metastatic gastric cancer.,
ASCO Gastrointestinal Cancers Symposium(ASCO-GI 2020), San Francisco, Jan. 2020.

(出版サイトへのリンク): ● Publication site (DOI): 10.1200/JCO.2020.38.4_suppl.297
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1200/JCO.2020.38.4_suppl.297

(DOI: 10.1200/JCO.2020.38.4_suppl.297) Sagawa Tamotsu, Yasushi Sato, Hamaguchi Kyoko, Hirakawa Masahiro, Nagashima Hiroyuki, Waga Eriko, Fujikawa Koshi and Takahashi Yasuo :
Conversion gastrectomy for stage IV unresectable gastric cancer: A retrospective cohort study.,
ASCO Gastrointestinal Cancers Symposium(ASCO-GI 2020), San Francisco, Jan. 2020.

(出版サイトへのリンク): ● Publication site (DOI): 10.1200/JCO.2020.38.4_suppl.298
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1200/JCO.2020.38.4_suppl.298

(DOI: 10.1200/JCO.2020.38.4_suppl.298) Yasushi Sato, Hideki Ishikawa and Tetsuji Takayama :
Capsule endoscopy for small intestinal surveillance in patients with familial adenomatous polyposis.,
JDDW2019(第27回日本消化器関連学会週間), Kobe, Nov. 2019. Naoki Muguruma, Daisaku Fujimot, Tomoyuki Kawaguchi, Kaizoh Kagemoto, Satoshi Teramae, Yoshifumi Kida, Hironori Wada, Fumika Nakamura, Yasuteru Fujino, Shinji Kitamura, Koichi Okamoto, Hiroshi Miyamoto, Toshihito Tanahashi, Hiroshi Miyamoto, Yasushi Sato and Tetsuji Takayama :
Linked Color Imaging Improves Detection Rate of Sessile Serrated Adenoma/Polyp in the Colon: A Prospective Randomized Controlled Trial.,
UEG Week 2019, Barcelona, Oct. 2019. Yasushi Sato, Tadahiko Nakagawa, Toshihito Tanahashi, Shinji Kitamura, Hiroshi Miyamoto, Koichi Okamoto, Naoki Muguruma and Tetsuji Takayama :
JMJD2A is a novel epigenetic factor of chemotherapeutic susceptibility in gastric cancer.,
The ESMO Congress 2019, Barcelona, Sep. 2019.

(出版サイトへのリンク): ● Publication site (DOI): 10.1093/annonc/mdz239.077
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1093/annonc/mdz239.077

(DOI: 10.1093/annonc/mdz239.077) Hironori Tanaka, Tetsu Tomonari, Takahiro Tanaka, Akihiro Hirao, Fumika Nakamura, Kumiko Tanaka, Koichi Okamoto, Yasushi Sato, Masahiro Sogabe, Hiroshi Miyamoto, Naoki Muguruma and Tetsuji Takayama :
Therapeutic efficacy of chemoradiotherapy with Miriplatin for hepatocellular carcinoma.,
digestive disease week2019, San Diego, May 2019. Jinsei Miyoshi, Noriaki Murayama, Kumiko Tanaka, Takahiro Tanaka, Fumika Nakamura, Yasuteru Fujino, Keiichiro Matsumura, Miwako Kagawa, Tetsu Tomonari, Shinji Kitamura, Koichi Okamoto, Hiroshi Miyamoto, Yasushi Sato, Naoki Muguruma and Tetsuji Takayama :
Development of a Novel Mirna-Based Signature to Predict Invasion and Metastasis in Rectal Neuroendocrine Tumors.,
digestive disease week2019, Vol.156, No.6, 133, San Diego, May 2019.

(出版サイトへのリンク): ● Publication site (DOI): 10.1016/S0016-5085(19)37123-9
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1016/S0016-5085(19)37123-9

(DOI: 10.1016/S0016-5085(19)37123-9) Jun Okazaki, Toshihito Tanahasi, Yasushi Sato, Jinsei Miyoshi, Tadahiko Nakagawa, Tetsuo Kimura, Hiroshi Miyamoto, Yasuteru Fujino, Fumika Nakamura, Masanori Takehara, Masahiro Bando, Shinji Kitamura, Koichi Okamoto, Naoki Muguruma, Masahiro Sogabe and Tetsuji Takayama :
Interaction Between Pancreatic Cancer Cells and Adipocytes Promote Pancreatic Cancer Progression Through Overexpression of Saa1.,
digestive disease week2019, San Diego, May 2019. Tamotsu Sagawa, Yasushi Sato, Hidetoshi Ohta, Kyoko Hamaguchi, Eriko Waga, Hiroyuki Nagashima, Shogo Miura, Koshi Fujikawa and Yasuo Takahashi :
CLINICAL USEFULNESS OF CLASSIFICATION BY CAPSULE ENDOSCOPY FOR DETECTION OF RADIATION ENTERITIS, Gastrointestinal Endoscopy, --- Su1324 ---,
Gastrointestinal Endoscopy, Vol.89, No.6, AB332, San Diego, California, May 2019.

(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.gie.2019.03.451
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1016/j.gie.2019.03.451

(DOI: 10.1016/j.gie.2019.03.451) Tetsuji Takayama, Toshihito Tanahashi, Koichi Okamoto, Shota Fujimoto, Tadahiko Nakagawa, Kaizoh Kagemoto, Yasuyuki Okada, Fumika Nakamura, Yasuteru Fujino, Shinji Kitamura, Hiroshi Miyamoto, Yasushi Sato and Naoki Muguruma :
S100P as a novel hypomethylation target in Sessile Serrated Adenoma(SSA/P)-cancer sequence: A genome-wide DNA methylation array analysis.,
UEG Week2018, Wien, Oct. 2018. Jinsei Miyoshi, Noriaki Murayama, Tadahiko Nakagawa, Tetsu Tomonari, Shinji Kitamura, Koichi Okamoto, Hiroshi Miyamoto, Yasushi Sato, Naoki Muguruma and Tetsuji Takayama :
Mir-144-3P/451A as a Novel Biomarker for Predicting Recurrence and Metastasis in Rectal Neuroendocrine Tumors Through Targeting Pten/P19.,
Digestive Disease Week 2018, Washington, D.C., Jun. 2018. Fumika Nakamura, Koichi Okamoto, Kumiko Tanaka, Yasuteru Fujino, Jinsei Miyoshi, Shinji Kitamura, Hiroshi Miyamoto, Yasushi Sato, Naoki Muguruma and Tetsuji Takayama :
Clinicopathological Analyses of Colorectal Polyps and Cancers in Serrated Polyposis Syndrome.,
DIgestive Disease Week2018, Washington, D.C., Jun. 2018. Tamotsu Sagawa, Kyoko Hamaguchi, Naomi Uemura, Fumito Tamura, Koshi Fujikawa, Yasushi Sato and Yasuo Takahashi :
Treatment strategy for metastatic colorectal cancer (mCRC) treated with chemotherapy plus biological targeted agent: Is strategy with biological targeted agent based on the primary tumor lesion possible?,
GASTROINTESTINAL CANCERS SYMPOSIUM, Jan. 2018. Yasushi Sato, Tamotsu Sagawa, Yasuo Takahashi, Hiroyuki Ohnuma, Kyoko Hamaguchi, Masahiro Hirakawa, Koshi Fujikawa, Koichi Okamoto, Hiroshi Miyamoto, Naoki Muguruma and Tetsuji Takayama :
A dose-escalation study of docetaxel, oxaliplatin and S-1 (DOS) as a first-line therapy for patients with unresectable metastatic gastric cancer.,
2018 Gastrointestinal Cancers Symposium, San Francisco, Jan. 2018. Yasushi Sato, Hiroyuki Ohnuma, Koichi Okamoto, Hiroshi Miyamoto, Masahiro Hirakawa, Naoki Uemura, Shohei Kikuchi, Tamotsu Sagawa, Koji Fujikawa, Yasuo Takahashi, Toshinori Okuda, Shinya Minami, Minoru Takahashi, Tetsuro Okamoto, Junji Kato and Tetsuji Takayama :
Phase II study of modified docetaxel, cisplatin and S-1 (mDCS) combination chemotherapy in patients with unresectable metastatic gastric cancer,
ESMO 2017 Congress, Madrid, Spain, Madrid, Sep. 2017. Tamotsu Sagawa, Hidetoshi Ohta, Yasushi Sato, Yasuhiro Sato, Tsuyoshi Hayashi, Tokiko Nakamura, Koshi Fujikawa and Yasuo Takahashi :
Assessment Tool to Evaluate Competency of Capsule Endoscopy Pre-Reader, Gastrointestinal Endoscopy,
Gastrointestinal Endoscopy, Vol.81, No.5, AB475, Washington, DC, Jan. 2015.

(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.gie.2015.03.1703
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1016/j.gie.2015.03.1703

(DOI: 10.1016/j.gie.2015.03.1703) Yasushi Sato, Tetsuji Takayama, Hiroyuki Ohnuma, Masahiro Hirakawa, Takahiro Osuga, Hiroshi Miyamoto, Tamotsu Sagawa, Yasuhiro Sato, Yasuo Takahashi, Shinichi Katsuki, Kohichi Takada, Tokunori Okuda, Tsuyoshi Hayashi, Tsutomu Sato, Koji Miyanishi, Rishu Takimoto, Masayoshi Kobune, Takayuki Nobuoka, Koichi Hirata and Junji Kato :
Trastuzumab (T-mab) in combination with docetaxel/cisplatin/S-1 (DCS) for patients with HER2-positive metastatic gastric cancer: Feasibility and preliminary efficacy.,
2014 Gastrointestinal Cancers Symposium, San Francisco, Jan. 2014. Yasushi Sato, Tetsuji Takayama, Tamotsu Sagawa, Yasuo Takahashi, Hiroyuki Ohnuma, Syunichi Okubo, Naoaki Shintani, Shingo Tanaka, Masaya Kida, Yasuhiro Sato, Hidetoshi Ohta, Koji Miyanishi, Tsutomu Sato, Rishu Takimoto, Masayoshi Kobune, Koji Yamaguchi, Koichi Hirata, Yoshiro Niitsu and Junji Kato :
Phase II study of S-1, docetaxel and cisplatin combination chemotherapy in patients with unresectable metastatic gastric cancer.,
Cancer Chemotherapy and Pharmacology, Vol.66, No.4, 721-728, 2010.

(要約): We evaluated the activity and toxicity of docetaxel, cisplatin, and S-1 (DCS) combination chemotherapy in patients with unresectable metastatic gastric cancer.
(キーワード): Adult / Aged / Antimetabolites, Antineoplastic / Antineoplastic Agents / Antineoplastic Agents, Phytogenic / Antineoplastic Combined Chemotherapy Protocols / Cisplatin / Dose-Response Relationship, Drug / Drug Combinations / Female / Granulocyte Colony-Stimulating Factor / Humans / Kaplan-Meier Estimate / Male / Middle Aged / Neoplasm Invasiveness / Neoplasm Metastasis / Neutropenia / Oxonic Acid / Stomach Neoplasms / Survival Analysis / Taxoids / Tegafur / Treatment Outcome
(出版サイトへのリンク): ● Publication site (DOI): 10.1007/s00280-009-1215-2
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20041328; ● Search Scopus @ Elsevier (PMID): 20041328; ● Search Scopus @ Elsevier (DOI): 10.1007/s00280-009-1215-2

(DOI: 10.1007/s00280-009-1215-2, PubMed: 20041328) 宮本弘志, 上田浩之, 三宅孝典, 髙橋拓, 横山怜子, 岡田泰行, 曽我部正弘, 佐藤康史, 高山哲治 :
膵癌における相同組換え修復欠損とプラチナ製剤を含む化学療法の関連.,
JDDW2024, 2024年11月. Hiroshi Miyamoto, Ayuka Mineda, Sawaka Yukishige, Soichiroh Sasa, Kei Daizumoto, Tomoya Fukawa, Yasuyuki Okada, Yasuhiro Mitsui, Koichi Okamoto, Yasushi Sato, Hiroyuki Morino and Tetsuji Takayama :
Management of patients with presumed germline pathogenic variant from comprehensive genomic profiling tests.,
日本人類遺伝学会第69回大会, Oct. 2024. 河野豊, 福田伊津子, 田中真樹, 佐藤康史, 高山哲治 :
KUHIMMiBを用いたエゾウコギの腸内細菌叢への影響.,
クロレラ・機能性植物研究会第6回研究集会, 2024年9月. 川口智之, 岡本耕一, 藤本将太, 上田浩之, 和田浩典, 宮本弘志, 佐藤康史, 六車直樹, 高山哲治 :
オルガノイド培養を用いたSessile serrated lesion の動物モデルの樹立とLansoprazole の⼤腸癌予防効果の検討.,
第31回日本がん予防学会総会(日本がん予防学会学術大会2024徳島), 2024年9月. 三橋威志, 河野豊, 佐藤康史, 友成哲, 田中宏典, 米澤真衣, 高山哲治 :
フィトケミカル食品エゾウコギを用いたMAFLD/MASH に対する有効性の基礎検討.,
第31回日本がん予防学会総会(日本がん予防学会学術大会2024徳島), 2024年9月. 川口智之, 岡本耕一, 三橋威志, 吉本貴則, 影本開三, 喜田慶史, 三井康裕, 中村文香, 佐藤康史, 高山哲治 :
<ワークショップ>Serrated polyposis syndromeの右側及び左側大腸病変の臨床病理学的差異の解析.,
第110回日本消化器病学会総会, 2024年5月. 樫原孝典, 三宅孝典, 岡本耕一, 河野豊, 六車直樹, 佐藤康史, 高山哲治 :
<ワークショップ>蛍光標識フラグメント化抗c-KIT抗体を用いた消化管間質腫瘍(GIST)の蛍光内視鏡診断の試み.,
第110回日本消化器病学会総会, 2024年5月. 吉本貴則, 岡本耕一, 上田浩之, 川口智之, 影本開三, 喜田慶史, 三井康裕, 中村文香, 佐藤康史, 高山哲治 :
<ワークショップ>Gastric adenocarcinoma and proximal polyposis of the stomach(GAPPS)の表現型とHelicobacter pylori(HP)感染症の関連についての検討.,
第110回日本消化器病学会総会, 2024年5月. 喜田慶史, 岡久稔也, 佐藤康史, 藤本将太, 川口智之, 中村文香, 岡本耕一, 宮本弘志, 曽我部正弘, 高山哲治 :
<シンポジウム>潰瘍性大腸炎におけるウロキナーゼ型プラスミノーゲンアクチベーター(uPA)の発現解析と治療標的としての意義.,
第110回日本消化器病学会総会, 2024年5月. 上田浩之, 藤本将太, 吉本貴則, 川口智之, 影本開三, 喜田慶史, 三井康裕, 岡本耕一, 佐藤康史, 高山哲治 :
<ワークショップ>ヒト由来大腸癌オルガノイドを用いたTIMP1の右側大腸癌の予後不良因子としての検討.,
第110回日本消化器病学会総会, 2024年5月. 河野豊, 友成哲, 佐藤康史, 高山哲治 :
MAFLD/MASHマウスモデルを用いたフィトケミカル含有食品エゾウコギの基礎検討.,
第42回Cytoprotection研究会, 2024年3月. 福家慧, 佐藤康史, 岡田泰行, 岡本耕一, 河野豊, 宮本弘志, 高山哲治, 影本開三, 喜田慶史 :
UBR4 は EGFR の内在化を制御することで，大腸癌患者における抗 EGFR 抗体の新規バイオマーカーとなる.,
第21回日本臨床腫瘍学会学術集会, 2024年2月. 横山怜子, 中村文香, 藤本将太, 樫原孝典, 曽我部正弘, 佐藤康史, 高山哲治 :
直腸原発悪性黒色腫に対する免疫チェックポイント阻害剤の有効性と免疫関連副作用の関連性.,
第20回日本消化管学会総会学術集会, 2024年2月. 川口智之, 岡本耕一, 藤本将太, 上田浩之, 曽我部正弘, 佐藤康史, 高山哲治 :
Stage I食道癌に対するESD後追加CRTの治療成績に関する検討.,
第20回日本消化管学会総会学術集会, 2024年2月. 藤本将太, 樫原孝典, 三宅孝典, 岡本耕一, 河野豊, 宮本弘志, 曽我部正弘, 佐藤康史, 高山哲治 :
抗c-KIT抗体フラグメントと近赤外蛍光内視鏡を用いた水分子イメージングおよび光治療によるGISTの新規診断治療法の開発.,
第20回日本消化管学会総会学術集会, 2024年2月. 岡本耕一, 勢井萌都子, 藤本将太, 三橋威志, 吉本貴則, 川口智之, 影本開三, 喜田慶史, 三井康裕, 中村文香, 佐藤康史, 高山哲治 :
Serrated polyposis syndromeの右側及び左側大腸病変の臨床病理学的および分子生物学的解析,
第10回消化管ポリポーシス研究会, 2024年1月. 横山怜子, 佐藤康史, 中村文香, 川口智之, 影本開三, 喜田慶史, 三井康裕, 藤野泰輝, 岡本耕一, 河野豊, 宮本弘志, 高山哲治 :
直腸悪性黒色腫に対する免疫チェックポイント阻害剤の効果予測因子としての irAE の意義.,
第 61 回日本癌治療学会学術集会, 2023年10月. 河野豊, 渡邉奈々恵, 西山正彦, 小野薫, 佐藤康史, 照井健, 日下部俊郎, 友成哲, 田中宏典, 高山哲治 :
がん関連疲労に対するエゾウコギ含有食品の実行可能性試験.,
第 61 回日本癌治療学会学術集会, 2023年10月. 河野豊, 田中真樹, 藤島雅基, 奥村衣梨, 竹腰英夫, 武田秀勝, 佐藤康史, 高山哲治 :
脂肪肝モデルマウスを用いた，エゾウコギによる治療応用に向けての基礎研究第2報.,
クロレラ・機能性植物研究会第5回研究集会, 2023年10月. 川口智之, 岡本耕一, 藤本将太, 上田浩之, 和田浩典, 宮本弘志, 佐藤康史, 六車直樹, 高山哲治 :
Connectivity Mapによる大腸癌予防薬の網羅的解析とSessile serrated lesionのオルガノイドを用いた抑制効果の検討.,
がん予防学術大会2023金沢, 2023年9月. 大木元彩夏, 岡本耕一, 高橋叡, 藤本将太, 吉本貴則, 三橋威志, 川口智之, 影本開三, 喜田慶史, 三井康裕, 中村文香, 佐藤康史, 高山哲治 :
内視鏡による積極的大腸ポリープ摘除術を施行しているリンチ症候群の一例.,
第5回がんゲノム医療時代におけるLynch症候群研究会学術集会, 2023年8月. 友成哲, 田中宏典, 河野豊, 佐藤康史, 高山哲治 :
デュルバルマブ+トレメリムマブ併用療法を見据えた肝細胞癌に対するアテゾリズマブ+ベバシズマブ併用療法の治療戦略.,
第28回日本肝がん分子標的治療研究会, 2023年6月. 佐藤康史, 岡本耕一, 高山哲治, 六車直樹, 中山圭子, 大住省三, 久保宜明, 内野眞也, 阪埜浩司, 石川秀樹 :
<作業部会委員会企画>Cowden症候群/PTEN hamartoma tumor syndrome (PHTS)の前向き登録コホート研究の概要.,
第29回日本遺伝性腫瘍学会学術集会, 2023年6月. 平田圭市郎, 上田浩之, 三宅孝典, 樫原孝典, 岡田泰行, 田中宏典, 和田浩典, 藤野泰輝, 友成哲, 谷口達哉, 岡本耕一, 宮本弘志, 川中崇, 生島仁史, 坂東良美, 佐藤康史, 高山哲治 :
切除不能・再発膵神経内分泌腫瘍(pancreatic neruoendocrine neoplasm:P-NEN)に対する集学的治療による治療成績の向上.,
第109回日本消化器病学会総会, 2023年4月. 川口智之, 岡本耕一, 藤本将太, 上田浩之, 和田浩典, 宮本弘志, 佐藤康史, 六車直樹, 高山哲治 :
前癌病変Sessile serrated lesionのオルガノイドを用いたLansoprazoleの抑制効果およびその機序の検討.,
第40回サイトプロテクション研究会, 2023年3月. Tetsu Tomonari, Yasushi Sato, Hironori Tanaka, Tatsuya Taniguchi, Yutaka Kawano, Tsutomu Masaki and Tetsuji Takayama :
アテゾリズマブ+ベバシズマブ，レンバチニブを用いた切除不能肝細胞癌に対する根治的Conversion therapyの治療成績.,
第20回日本臨床腫瘍学会学術集会, Mar. 2023. 藤井祥平, 北村晋志, 三井康裕, 佐藤康史, 高山哲治 :
ボノプラザン長期投与後に胃ポリポーシスを発症し，胃上皮性腫瘍を認めた透析患者の1例.,
第95回日本胃癌学会総会, 2023年2月. 川口智之, 岡本耕一, 和田浩典, 佐藤康史, 六車直樹, 高山哲治 :
前癌病変 Sessile serrated lesion のオルガノイドを用いた Lansoprazole の抑制効果およびその機序の検討.,
第19回日本消化管学会総会学術集会, 2023年2月. 上田浩之, 川口智之, 和田浩典, 中村文香, 北村晋志, 岡本耕一, 佐藤康史, 高山哲治 :
右側大腸癌における TIMP1 の予後不良因子としての意義:右側及び左側大腸癌を比較して.,
第19回日本消化管学会総会学術集会, 2023年2月. 岡本耕一, 中村文香, 八木麻衣, 岡田明子, 藤井祥平, 吉本貴則, 横山怜子, 川口智之, 影本開三, 喜田慶史, 三井康裕, 佐藤康史, 高山哲治 :
Serrated polyposis syndrome に合併した大腸腺腫の臨床病理学的特徴.,
第98回大腸癌研究会学術集会, 2023年1月. 佐藤康史 :
食道癌・胃癌の薬物治療,
日本消化器病学会四国支部第42回教育講演会, 2022年12月. 影本開三, 中村文香, 岡本耕一, 吉本貴則, 川口智之, 横山怜子, 喜田慶史, 三井康裕, 北村晋志, 宮本弘志, 佐藤康史, 高山哲治 :
鋸歯状ポリポーシス症候群における大腸腫瘍の病理像と発癌機序についての解析.,
第60回癌治療学会学術集会, 2022年10月. Beibei Ma, Hiroyuki Ueda, Koichi Okamoto, Masahiro Bando, Yasuyuki Okada, Mitsuo Shimada, Yasushi Sato and Tetsuji Takayama :
TIMP1 Promotes Cell Proliferation and Invasion Capability of Right-sided Colon Cancers.,
第81回日本癌学会学術総会, Sep. 2022. 田中久美子, 岡本耕一, 佐藤康史, 高山哲治, 六車直樹, 石川秀樹, 竹内洋司, 武藤倫弘 :
家族性大腸腺腫症における小腸病変の形態学的解析.,
第10回日本家族性大腸腺腫症研究会学術集会, 2022年9月. 佐藤康史 :
胃がん治療について,
第20回徳島県がん登録研修会, 2022年8月. 佐藤康史 :
胃がんに対する新しい抗体薬物療法,
Cancer meeting in Tokushima 2022, 2022年8月. 中村文香, 岡本耕一, 影本開三, 平田圭市郎, 吉本貴則, 横山怜子, 川口智之, 喜田慶史, 三井康裕, 田中久美子, 北村晋志, 佐藤康史, 高山哲治 :
Serrated polyposis syndromeにおける発癌リスクとその予防.,
第29回日本がん予防学会総会, 2022年7月. 平尾章博, 佐藤康史, 田中宏典, 田中貴大, 友成哲, 谷口達哉, 岡本耕一, 六車直樹, 西田憲生, 高山哲治 :
肝細胞癌においてmiR-125b-5pは上皮間葉転換を引き起こし，ソラフェニブに対して耐性を獲得する,
第19回日本臨床腫瘍学会学術集会, 2022年2月. Yasuyuki Okada, Yasuhiro Mitsui, Shinji Kitamura, Koichi Okamoto, Hiroshi Miyamoto, Yasushi Sato, Naoki Muguruma and Tetsuji Takayama :
LAMC2 is a novel predictive biomarker for gemcitabine-based therapy in pancreatic ductal adenocarcinoma.,
第19回日本臨床腫瘍学会学術集会, Feb. 2022. 川口智之, 岡本耕一, 板東正浩, 上田浩之, 和田浩典, 宮本弘志, 佐藤康史, 六車直樹, 高山哲治 :
前癌病変Sessile serrated lesionのオルガノイドを用いた大腸癌予防薬の開発∼Connectivity Mapを用いた網羅的な分析∼,
第18回日本消化管学会学術集会, 2022年2月. 友成哲, 谷丈二, 田中宏典, 田中宏典, 田中貴大, 谷口達哉, 森下朝洋, 佐藤康史, 正木勉, 高山哲治 :
後治療を見据えた肝細胞癌に対するアテゾリズマブ+ベバシズマブ併用療法の治療戦略.,
第25回日本肝がん分子標的治療研究会, 2022年1月. 佐藤康史, 高山哲治, 石川秀樹, 武藤倫弘, J-FAPP Study IVグループ :
家族性大腸腺腫症患者に対する低用量アスピリン，メサラジンによる化学予防(J-FAPP IV Study).,
第76回日本大腸肛門病学会学術集会, 2021年11月. 野田和克, 佐藤康史, 高山哲治 :
癌関連脂肪細胞に由来するエクソソーム内miRNAを介した膵癌進展機構の検討.,
JDDW2021(第29回日本消化器医関連学会週間), 2021年11月. 平尾章博, 佐藤康史, 高山哲治 :
肝細胞癌におけるソラフェニブ耐性化バイオマーカーとしてのmiR125b-5p-ATXN1 axisの有用性.,
JDDW2021(第29回日本消化器医関連学会週間), 2021年11月. 村山典聡, 岡本耕一, 三好人正, 川口智之, 北村晋志, 馬貝貝, 宮本弘志, 六車直樹, 佐藤康史, 高山哲治 :
miR-144-3p/miR-451aは，PTEN/p19を介して直腸カルチノイド(NET-G1)の浸潤に関与する.,
第59回日本癌治療学会学術集会, 2021年10月. 田中宏典, 友成哲, 影本開三, 岡田泰行, 和田浩典, 中村文香, 北村晋志, 岡本耕一, 宮本弘志, 佐藤康史, 六車直樹, 高山哲治 :
免疫チェックポイント阻害薬投与中の肝障害.,
第59回日本癌治療学会学術集会, 2021年10月. Akinari Kasai, Jinsei Miyoshi, Akihiro Haga, Takashi Kawanaka, Koichi Okamoto, Naoki Muguruma, Yasushi Sato and Tetsuji Takayama :
CT-based AI radiomics model for predicting complete response and progression free survival of chemoradiothearapy in ESCC.,
第80回日本癌学会学術総会, Oct. 2021. Beibei Ma, Hiroyuki Ueda, Naoki Muguruma, Koichi Okamoto, Tomoyuki Kawaguchi, Akira Fukuya, Yoshifumi Kida, Yasuyuki Okada, Tatsuya Taniguchi, Yasushi Sato and Tetsuji Takayama :
Activation of EGFR signaling pathway in the left-side colorectal cancerLeft-side vs. right-side cancer organoids.,
第80回日本癌学会学術総会, Sep. 2021. 田中育太, 友兼毅, 門田美由香, 多田早織, 小田修治, 佐藤康史, 六車直樹 :
当院における進行再発胃癌に対しFOLFOX療法を施行した症例の検討.,
第107回日本消化器病学会総会, 2021年4月. 野田和克, 佐藤康史, 高山哲治 :
癌関連脂肪細胞の分泌型exosome内miRNAプロファイル解析による膵癌進展機序の検討.,
第107回日本消化器病学会総会, 2021年4月. 矢野庄悟, 中村文香, 佐藤康史, 福家慧, 藤野泰輝, 北村晋志, 岡本耕一, 宮本弘志, 六車直樹, 高山哲治 :
消化管悪性腫瘍における免疫チェックポイント阻害薬の効果と免疫関連副作用の関連性について.,
第17回日本消化管学会総会学術集会, 2021年2月. 中村文香, 岡本耕一, 影本開三, 喜田慶史, 田中久美子, 北村晋志, 佐藤康史, 宮本弘志, 六車直樹, 高山哲治 :
Serrated polyposis syndrome に合併した大腸癌の臨床病理学的特徴ならびに発癌機序の検討.,
第17回日本消化管学会総会学術集会, 2021年2月. 上田浩之, Yasuhiro Mitsui, 滝下誠, 矢野充保, 福家慧, Tomoyuki Kawaguchi, Yoshifumi Kida, Shinji Kitamura, Koichi Okamoto, Yasushi Sato, Naoki Muguruma and Tetsuji Takayama :
Clinicopathological analysis of six families with Gastric Adenocarcinoma and Proximal Polyposis of the Stomach(GAPPS).,
第18回日本臨床腫瘍学会学術集会, Feb. 2021. 矢野庄悟, 寺前智史, 田中久美子, 藤野泰輝, 岡本耕一, 佐藤康史, 六車直樹, 高山哲治, 佐々木悠, 八島一夫, 大瀬戸久美子, 石川秀樹 :
本邦におけるCowden症候群の実態調査.,
第7回消化管ポリポーシス研究会学術集会, 2021年1月. 芳川明奈, 三好人正, 笠井昭成, 松本れいか, 宮城愛, 宮本弘志, 佐藤康史, 六車直樹, 北研二, 高山哲治 :
AI-based ESCC miRNA diagnosis model: retro-prospective multinational cohort study.,
第74回日本食道学会学術集会, 2020年12月. 佐藤康史, 棚橋俊仁, 中川忠彦, 北村晋志, 宮本弘志, 岡本耕一, 六車直樹, 高山哲治 :
JMJD2Aヒストン脱メチル化酵素はCCDC8と協調し胃癌に対する化学療法感受性を制御する.,
第58回日本癌治療学会学術集会, 2020年10月. 横山怜子, 中村文香, 佐藤康史, 岸和弘, 和田浩典, 友成哲, 北村晋志, 岡本耕一, 宮本弘志, 六車直樹, 岡久稔也, 高山哲治 :
胃癌におけるICI治療の効果予測因子としてのirAEの意義とその後治療への影響.,
第58回日本癌治療学会学術集会, 2020年10月. 佐藤康史 :
胃がんに対する薬物療法のup to date,
令和2年度徳島大学大学院市民公開講座中国四国広域がんプロ養成コンソーシアムがん治療の最前線, 2020年10月. Jinsei Miyoshi, Shusuke Toden, Daisuke Izumi, Mitsuro Kanda, Yasushi Sato, Naoki Muguruma, Hideo Baba, Yasuhiro Kodera, Ajay Goel and Tetsuji Takayama :
Circulating miRNA signature of esophageal squamous cell carcinoma diagnosis: retro-prospective multinational cohort study.,
第79回日本癌学会学術総会, Oct. 2020. 川口智之, 藤本将太, 板東正浩, 上田浩之, 和田浩典, 岡本耕一, 宮本弘志, 佐藤康史, 六車直樹, 高山哲治 :
Connectivity Map とsessile serrated lesion オルガノイドを用いた網羅的な大腸癌予防薬の検索.,
がん予防学術大会2020米子, 2020年9月. 友成哲, 佐藤康史, 高山哲治 :
レンバチニブのソラフェニブ既治療肝癌に対する有効性の検討ー実臨床データとプロテインアレイ解析ー.,
第56回日本肝臓学会総会, 2020年8月. 藤井祥平, 中村文香, 佐藤康史, 岸和弘, 吉田守美子, 三井康裕, 藤野泰輝, 北村晋志, 岡本耕一, 宮本弘志, 六車直樹, 高山哲治 :
<第23回若手奨励賞>胃癌における免疫チェックポイント阻害薬の効果と免疫関連副作用(irAE)との関連性についての検討.,
四国医学雑誌, Vol.76, No.3-4, 173-178, 2020年8月.

(要約): Recently, immune checkpoint inhibitors(ICI)have been approved for use in advanced gastric cancer(AGC)based on the positive results of ATTRACTION‐2 trial in Japan. There has been accumulating evidence that the development of immune-related adverse events(irAE)may be associated with a response to ICI therapy, particularly in lung cancer, although little is known about these correlations in gastrointestinal cancer. To investigate the efficacy and irAE of ICI treatment and their correlation in AGC, we retrospectively examined 29 patients with AGC who received nivolumab therapy in our departments. Among them, 15 patients(52%)developed irAEs including 4 patients(14%)for grade 3 irAEs ; liver dysfunction(n＝2), type 1 diabetes mellitus(n＝2) and adrenal insufficiency(n＝1). The median overall survival was12．0months in the irAE group and 3．25 months in the non-irAE group(p＝0．164), which suggested the relationship between the effects and irAEs in ICI treatment of AGC. Further research is required to understand the implications of irAE characteristics on ICI response in GCA patients.
(キーワード): Immune-checkpoint inhibitors / Gastric cancer / Immune-related adverse events / Nivolumab
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1050865265018642176

(CiNii: 1050865265018642176) 友成哲, 佐藤康史, 高山哲治 :
ソラフェニブ既治療肝癌に対するレンバチニブの治療効果の検討―実臨床データとプロテインアレイ解析―.,
第106回日本消化器病学会総会, 2020年8月. 平尾章博, 佐藤康史, 高山哲治 :
肝細胞癌においてmiR-125b-5pはATXN1を介したEMT制御によりソラフェニブ耐性化に関与する.,
第106回日本消化器病学会総会, 2020年8月. 樫原孝典, 宮本佳彦, 藤本将太, 和田浩典, 川口智之, 喜田慶史, 中村文香, 田中久美子, 北村晋志, 岡本耕一, 宮本弘志, 佐藤康史, 六車直樹, 高山哲治 :
大腸腫瘍に発現するepidermal growth factor receptor in colorectal tumors.,
第16回日本消化管学会総会学術集会, 2020年2月. 中村文香, 岡本耕一, 影本開三, 田中久美子, 藤野泰輝, 北村晋志, 宮本弘志, 佐藤康史, 六車直樹, 高山哲治 :
Serrated polyposis syndrome の臨床病理学的特徴ならびに発癌機序の検討.,
第16回日本消化管学会総会学術集会, 2020年2月. 川口智之, 武原正典, 影本開三, 寺前智史, 中村文香, 田中貴大, 北村晋志, 岡本耕一, 宮本弘志, 佐藤康史, 六車直樹, 高山哲治 :
胸腺を含む5臓器にわたって10個の同時性多発重複癌を呈したLynch症候群の一例 .,
第57回日本癌治療学会学術集会, 2019年10月. 武原正典, 佐藤康史, 川口智之, 野田和克, 福家慧, 北村晋志, 岡本耕一, 宮本弘志, 六車直樹, 高山哲治 :
癌関連脂肪細胞は膵癌のSAA1発現を誘導し，転移・浸潤を促進する.,
第57回日本癌治療学会学術集会, 2019年10月. Tadahiko Nakagawa, Toshihito Tanahashi, yoshihiko miyamoto, Jun Okazaki, masanori takehara, noriaki murayama, Jinsei Miyoshi, Tatsuya Taniguchi, Yoshimi Bando, Koichi Okamoto, Yasushi Sato, Naoki Muguruma and Tetsuji Takayama :
JMJD2A (KDM4A) sensitizes metastatic gastric cancer to chemotherapy by cooperating CCDC8.,
第78回日本癌学会学術総会, Sep. 2019. yoshihiko miyamoto, Naoki Muguruma, yasuyuki okada, Hironori Tanaka, Jun Okazaki, Koichi Okamoto, Yasushi Sato and Tetsuji Takayama :
EGFR-targeted molecular imaging for detection and treatment evaluation of colorectal tumors in animal model.,
第78回日本癌学会学術総会, Sep. 2019. Hironori Tanaka, Koichi Okamoto, 岡田泰行, 宮本佳彦, Yasuhiro Mitsui, Fumika Nakamura, Jinsei Miyoshi, Yasuteru Fujino, Takahiro Tanaka, Tetsu Tomonari, Shinji Kitamura, Hiroshi Miyamoto, Naoki Muguruma, Yasushi Sato and Tetsuji Takayama :
Therapeutic efficacy of miriplatin in combination with radiotherapy for advanced hepatocellular carcinoma.,
第17回日本臨床腫瘍学会学術集会, Jul. 2019. 三好人正, 村山典聡, 寺前智史, 宮本佳彦, 田中宏典, 岡田泰行, 三井康裕, 藤野泰輝, 田中貴大, 田中久美子, 松村圭一郎, 香川美和子, 友成哲, 北村晋志, 岡本耕一, 宮本弘志, 佐藤康史, 六車直樹, 高山哲治 :
直腸NETのmicroRNA網羅的発現解析を用いた転移機序の解明と新規転移予測バイオマーカーの探索.,
第17回日本臨床腫瘍学会学術集会, 2019年7月. 佐藤康史 :
消化器癌における癌予防臨床研究,
日本がん予防学会第3回認定制度セミナー, 2019年6月. 藤本将太, 六車直樹, 中尾允泰, 安藤英紀, 宮本佳彦, 岡本耕一, 佐藤康史, 石田竜弘, 佐野茂樹, 高山哲治 :
新規蛍光プローブIndocyanine green (ICG) 標識Dasatinibを用いた消化管間質腫瘍 (GIST) の近赤外蛍光イメージング.,
第14回日本分子イメージング学会総会・学術集会, 2019年5月. 佐藤康史, 岸和弘, 高山哲治 :
消化管腫瘍における免疫チェックポイント阻害薬の経験―自己免疫疾患関連副作用(irAE)の相違から―.,
第105回日本消化器病学会総会, 2019年5月. Yasuhiro Mitsui, Shinji Kitamura, Koichi Okamoto, Yasushi Sato, Naoki Muguruma and Tetsuji Takayama :
Clinicopathological characteristics of Gastric adenocarcinoma with proximal polyposis of the stomach.,
第91回日本胃癌学会総会, Mar. 2019. 佐藤康史, 佐川保, 高橋康雄, 大沼啓之, 平川昌宏, 信岡隆幸, 竹政伊知朗, 高山哲治 :
進行・再発胃癌に対するdocetaxel / oxaliplatin / S-1(DOS)療法の初期治療成績.,
第91回日本胃癌学会総会, 2019年2月. 三好人正, 村山典聡, 中川忠彦, 岡本耕一, 佐藤康史, 六車直樹, 西田憲生, 常山幸一, 藤盛孝博, 高山哲治 :
直腸NETのmiRNA-Gene-Pathwayを介した転移機序の解明とmiR-144-3p/451aの転移予測マーカーとしての意義.,
第15回日本消化管学会総会学術集会, 2019年2月. 藤本将太, 六車直樹, 岡本耕一, 佐藤康史, 宮本佳彦, 北村晋志, 宮本弘志, 高山哲治 :
近赤外蛍光標識c-KIT抗体を用いた消化管間質腫瘍(GIST)に対する新たな内視鏡診断治療法(Theranostics)の開発.,
第15回日本消化管学会総会学術集会, 2019年2月. 三井康裕, 田中久美子, 寺前智史, 北村晋志, 岡本耕一, 佐藤康史, 六車直樹, 高山哲治 :
Gastric adenocarcinoma with proximal polyposis of the stomach(GAPPS)家系における若年罹患者へのアプローチ.,
第5回日本消化管ポリポーシス研究会(日本消化器病学会関連研究会), 2019年1月. 佐藤康史 :
大腸癌化学療法のUp-to-date,
日本消化器病学会四国支部第34回教育講演会, 2018年11月. 藤本将太, 六車直樹, 岡本耕一, 佐藤康史, 宮本佳彦, 中尾允泰, 北村晋志, 宮本弘志, 佐野茂樹, 石田竜弘, 常山幸一, 高山哲治 :
Theranostics理論に基づく消化管間質腫瘍(GIST)の新規診断治療法の開発.,
第26回日本消化器関連学会週間(第96回日本消化器内視鏡学会総会), 2018年11月. 中村文香, 佐藤康史, 高山哲治 :
消化管腫瘍における免疫チェックポイント阻害薬の自己免疫疾患関連副作用(irAE)の経験,
第26回日本消化器関連学会週間(統合プログラム), 2018年11月. 和田浩典, 北村晋志, 中村文香, 福家慧, 武原正典, 岡田泰行, 三井康裕, 三好人正, 藤野泰輝, 田中久美子, 岡本耕一, 宮本弘志, 佐藤康史, 六車直樹, 高山哲治 :
CRT後咽頭狭窄を伴う表在型食道癌に対して細径内視鏡を用いたPDTが有効であった一例.,
第56回日本癌治療学会学術集会, 2018年10月. 福家慧, 佐藤康史, 佐川保, 高橋康雄, 大沼啓之, 濱口京子, 平川昌宏, 藤川幸司, 藤野泰輝, 岡本耕一, 六車直樹, 高山哲治 :
切除不能進行胃癌に対するドセタキセル/オキサリプラチン/S-1 3剤併用療法の第1相試験.,
第56回日本癌治療学会学術集会, 2018年10月. Jun Okazaki, Toshihito Tanahashi, Hironori Tanaka, Yasuyuki Okada, Yoshihiko Miyamoto, Jinsei Miyoshi, Tatsuya Taniguchi, Yasushi Sato, Naoki Muguruma and Tetsuji Takayama :
miR-296-5p inhibits apoptosis and enhances invasion through the down-regulated BOK in unresectable pancreatic cancer.,
第77回日本癌学会学術集会, Sep. 2018. Yoshihiko Miyamoto, Hironori Tanaka, Jun Okazaki, Yasuyuki Okada, Tatsuya Taniguchi, Yasushi Sato, Naoki Muguruma and Tetsuji Takayama :
Molecular imaging of colorectal tumor targeting epidermal growth factor receptor (EGFR).,
第77回日本癌学会学術集会, Sep. 2018. 中川忠彦, 棚橋俊仁, 宮本佳彦, 武原正典, 村山典聡, 田中宏典, 三好人正, 谷口達哉, 坂東良美, 岡本耕一, 佐藤康史, 六車直樹, 高山哲治 :
ヒストン脱メチル化酵素JMJD2Aは切除不能進行胃癌においてCCDC8の発現調節を介して抗癌剤感受性を制御する.,
第77回日本癌学会学術総会, 2018年9月. 寺前智史, 田中久美子, 三橋威志, 三井康裕, 中村文香, 藤野泰輝, 三好人正, 北村晋志, 岡本耕一, 宮本弘志, 佐藤康史, 六車直樹, 高山哲治 :
新規APC遺伝子変異(C.1626+1G>A)を認めた家族性大腸腺腫症の一例.,
第6回日本家族性大腸腺腫症研究会学術集会, 2018年9月. 佐藤康史 :
消化管がんの新しい薬物療法,
日本消化器病学会四国支部第80回市民公開講座, 2018年9月. 佐藤康史 :
消化器疾患に対する新たな治療開発の試み-消化器癌と肝硬変に対する治療を中心に-,
第221回徳島医学会学術集会, 2018年8月. 武原正典, 佐藤康史, 津保友香, 福家慧, 岡田泰行, 宮本佳彦, 三井康裕, 藤野泰輝, 中村文香, 北村晋志, 岡本耕一, 宮本弘志, 六車直樹, 高山哲治 :
膵癌と脂肪細胞の相互作用はSAA1の発現を誘導することにより膵癌の浸潤を促進させる.,
第16回日本臨床腫瘍学会学術集会, 2018年7月. 津保友香, 三井康裕, 福家慧, 武原正典, 岡田泰行, 三好人正, 藤野泰輝, 中村文香, 田中久美子, 北村晋志, 岡本耕一, 宮本弘志, 佐藤康史, 六車直樹, 高山哲治 :
切除不能進行神経内分泌癌に対するIrinotecan+Cisplatin併用療法の後方視的検討.,
第16回日本臨床腫瘍学会学術集会, 2018年7月. 大沼啓之, 早坂尚貴, 佐藤昌則, 平川昌宏, 西浩嗣, 佐川保, 藤川幸司, 大井雅夫, 岡川泰, 辻靖, 平山眞章, 佐藤康史, 伊東竜哉, 信岡隆幸, 竹政伊知朗, 加藤淳二 :
進行食道扁平上皮癌に対するdocetaxel， nedaplatin，5-fluorouracil(DNF)併用療法による術前補助化学療法の第Ⅱ相試験,
第16 回日本臨床腫瘍学会学術集, 2018年7月. 福家慧, 佐藤康史, 佐川保, 高橋康雄, 大沼啓之, 濱口京子, 平川昌宏, 藤川幸司, 藤野泰輝, 三井康裕, 岡田泰行, 北村晋志, 岡本耕一, 宮本弘志, 六車直樹, 高山哲治 :
切除不能進行胃癌に対するdocetaxel/ oxaliplatin/S-1(DOS)療法の第I相試験.,
第16回日本臨床腫瘍学会学術集会, 2018年7月. 友成哲, 新居徹, 津保友香, 宮本佳彦, 田中宏典, 田中貴大, 岡本耕一, 宮本弘志, 曽我部正弘, 佐藤康史, 六車直樹, 高山哲治 :
集学的治療奏功例を含む進行肝癌に対するRegorafenibの初期治療成績.,
第54回日本肝癌研究会, 2018年6月. 三井康裕, 田中久美子, 寺前智史, 北村晋志, 岡本耕一, 佐藤康史, 六車直樹, 高山哲治 :
Gastric adenocarcinoma with proximal polyposis of the stomach(GAPPS)におけるAPC 遺伝子生殖細胞系列変異および臨床病理学的特徴.,
第24回日本家族性腫瘍学会学術集会, 2018年6月. Hiroyuki Ohnuma, Teppei Matsuno, Chisa Fujita, Masahiro Hirakawa, Koji Miyanishi, Koichi Okamoto, Hiroshi Miyamoto, Yasushi Sato, Tetsuji Takayama and Junji Kato :
[WS4-5] Efficacy of DCS±T/DOS combination chemotherapy for gastric cancer with peritoneal metastasis,
Workshop 4 Treatment of gastric cancer patients with peritoneal dissemination 90th Annual Meeting of the Japanese Gastric Cancer Association, Mar. 2018. Shinji Kitamura, Naoki Muguruma, Yasushi Sato and Tetsuji Takayama :
New Traction Method with Endoloop for ESD.,
第90回日本胃癌学会総会, Mar. 2018. 中村文香, 岡本耕一, 影本開三, 村山典聡, 田中久美子, 藤野泰輝, 北村晋志, 三宮勝隆, 佐藤康史, 宮本弘志, 六車直樹, 高山哲治 :
Serrated polyposis syndromeにおける遺伝性及び発癌機序の検討.,
第14回日本消化管学会総会学術集会, 2018年2月. 藤野泰輝, 岡本耕一, 六車直樹, 三井康裕, 北村晋志, 藤本大策, 曽我部正弘, 宮本弘志, 佐藤康史, 高山哲治 :
microRNA arrayを用いた大腸粘膜下層浸潤癌リンパ節転移に関わるバイオマーカーの同定及び機能解析,
第14回日本消化管学会総会学術集会, 2018年2月. 岡田泰行, 木村哲夫, 岡本耕一, 中村文香, 藤野泰輝, 田中久美子, 三好人正, 三井康裕, 北村晋志, 宮本弘志, 佐藤康史, 六車直樹, 高山哲治 :
抗EGFR抗体薬治療におけるEarly tumor shrinkage(ETS)とEGFR内在化の関連について,
第88回大腸癌研究会, 2018年1月. 藤野泰輝, 野田和克, 村山典聡, 田中久美子, 北村晋志, 岡本耕一, 宮本弘志, 佐藤康史, 六車直樹, 岡久稔也, 高山哲治, 久保宜明, 坂東良美, 岡村誠介 :
胃巨大ポリープから出血をきたしたCowden病の一例.,
第4回消化管ポリポーシス研究会(日本消化器病学会関連研究会), 2018年1月. 藤本将太, 六車直樹, 岡本耕一, 佐藤康史, 宮本佳彦, 北村晋志, 宮本弘志, 高山哲治 :
Gastrointestinal stromal tumorに対するC-KITを標的とした新規近赤外蛍光イメージング診断と光抗体療法の開発.,
第3回G-PLUS, 2017年12月. 藤野泰輝, 池田敬洋, 友成哲, 三井康裕, 香川美和子, 佐藤桃子, 仁木美也子, 北村晋志, 木村哲夫, 岡本耕一, 宮本弘志, 佐藤康史, 六車直樹, 高山哲治 :
Ipilimumab にて完全奏功が得られた転移性直腸悪性黒色腫の1例.,
第 55 回日本癌治療学会学術集会,, 2017年10月. 中川忠彦, 棚橋俊仁, 木村哲夫, 岡本耕一, 谷口達哉, 村山典聡, 田中宏典, 坂東良美, 佐藤康史, 六車直樹, 高山哲治 :
ヒストン脱メチル化酵素JMJD2Aは切除不能進行胃癌において CCDC8の発現を調節することで薬剤感受性を制御している.,
第76回日本癌学会学術総会, 2017年9月. 村山典聡, 岡本耕一, 中川忠彦, 木村哲夫, 谷口達哉, 田中宏典, 佐藤康史, 六車直樹, 常山幸一, 藤盛孝博, 高山哲治 :
miR-144-3p/miR-451a はPTEN/p19 を抑制することにより直腸カルチノイド(NET-G1)の浸潤・転移に関与する.,
第76回日本癌学会学術総会, 2017年9月. 田中久美子, 寺前智史, 藤野泰輝, 岡本耕一, 佐藤康史, 六車直樹, 高山哲治, 小倉俊郎, 石畝亨, 石田秀行 :
胆管癌及び多発十二指腸癌を合併した家族性大腸腺腫症の一例.,
第5回日本家族性大腸腺腫症研究会学術集会, 2017年9月. 田中久美子, 寺前智史, 藤野泰輝, 岡本耕一, 佐藤康史, 六車直樹, 佐々木悠, 八島一夫, 大瀬戸久美子, 石川秀樹, 高山哲治 :
本邦におけるCowden病の実態調査.,
第23回日本家族性腫瘍学会学術集会, 2017年8月. 平川昌宏, 大沼啓之, 松野鉄平, 池田裕貴, 高橋稔, 岡本哲郎, 佐藤康史, 加藤淳二 :
切除不能進行再発大腸癌に対するTriplet+分子標的薬療法における原発巣の部位と治療効果の検討,
第15 回日本臨床腫瘍学会学術集, 2017年7月. 大沼啓之, 菊地尚平, 佐藤康史, 高田弘一, 宮西浩嗣, 加藤淳二 :
進行食道癌に対するdocetaxel，nedaplatin，5-FU(DNF)3剤併用療法を用いた集学的治療戦略,
第15回日本臨床腫瘍学会学術集会, 2017年7月. 藤野泰輝, 田中久美子, 中村文香, 北村晋志, 木村哲夫, 岡本耕一, 宮本弘志, 佐藤康史, 六車直樹, 高山哲治 :
大腸粘膜下層浸潤癌リンパ節転移に関わるmicroRNAの網羅的解析.,
第87回大腸癌研究会, 2017年7月. 影本開三, 岡本耕一, 岡田泰行, 高岡慶史, 三井康裕, 藤本大策, 北村晋志, 木村哲夫, 宮本弘志, 佐藤康史, 六車直樹, 高山哲治 :
画像強調内視鏡(IEE)によるヒト Aberrant crypt foci (ACF)の観察∼従来のメチレンブルー散布法と比較して∼.,
がん予防学術大会2017, 2017年6月. 佐藤康史 :
胃癌治療最近の話題 ~胃癌の薬物療法~,
第7回日本臨床腫瘍学会北海道地区セミナー, 2017年2月. 佐藤康史, 大沼啓之, 信岡隆幸, 平川昌宏, 菊池尚平, 佐川保, 高橋康雄, 辻靖, 高山哲治, 竹政伊知朗, 加藤淳二 :
切除不能進行胃癌に対する術前Docetaxel+Cisplatin+S-1(DCS)化学療法の長期成績.,
第54回日本癌治療学会学術集会, 2016年10月. 田中久美子, 六車直樹, 高山哲治, 佐藤康史, 加藤淳二 :
家族性大腸線種症における小腸病変の検討,
第2回日本家族性大腸線種症研究会学術集会, 2014年11月. 佐藤康史, 高山哲治 :
HER2陽性手術不能進行胃癌に対するDCS+Trastuzumab(DCS-T)併用化学療法の認容性試験,
第51回日本癌治療学会, 2013年10月. 佐藤康史, 高山哲治, 大沼啓之, 平川昌宏, 佐川保, 高橋康雄, 勝木伸一, 前田征洋, 高田弘一, 佐藤勉, 宮西浩嗣, 滝本理修, 小船雅義, 平田公一, 加藤淳二 :
DSC療法による切除不能胃癌に対するConversion therapyの可能性,
第10回臨床腫瘍学会学術集会, 2012年7月.

研究会・報告書: 佐藤康史 :
最新の大腸癌治療について,
第2回地方におけるがん治療を考える会, 2023年6月. 佐藤康史 :
最近の胃癌治療について,
第23回徳島消化器内科癌治療研究会, 2021年10月. 佐藤康史 :
切除不能大腸癌薬物療法のupdate,
東四国医療セミナー, 2021年7月. 佐藤康史 :
消化器内科の診療について,
高松市民みんなの病院地域連携セミナー, 2021年4月. 佐藤康史 :
resectabilityを追求した大腸癌薬物療法,
第10回札幌大腸癌治療連携セミナー, 2021年4月. 佐藤康史 :
胃癌化学療法∼新しいガイドラインを踏まえて∼,
白石Oncologyセミナー, 2021年3月. 佐藤康史 :
Triplet Regimen をどう活用するか,
大腸癌インタラクティブWeb講演会, 2020年9月. 佐藤康史 :
胃癌における二次治療の実際,
徳島消化器ガンセミナー, 2020年2月. 佐藤康史 :
胃癌とMSIについて,
徳島胃がん治療セミナー, 2019年11月. 佐藤康史 :
新ガイドラインを踏まえた大腸癌治療戦略,
第19回徳島消化器内科癌治療研究会, 2019年4月. 佐藤康史 :
大腸癌後方ラインにおける治療戦略,
徳島大腸癌化学療法講演会, 2018年7月. 佐藤康史 :
当科で経験した免疫チェックポイント阻害剤の副作用とリスクマネイジメント,
Educational seminar in Tokushima, 2017年12月. 佐藤康史 :
大腸がんに対するtriplet regimen-conversion therapyの可能性-,
Gastrointestinal cancer symposium 2017, 2017年10月. 佐藤康史 :
胃癌化学療法のup to date,
第16回徳島消化器内科癌治療研究会, 2017年9月. 佐藤康史 :
酸関連疾患における最近の話題∼逆流性食道炎の話題を中心に∼,
海部郡医師会学術講演会, 2017年8月. 佐藤康史 :
胃癌の薬物療法up to date,
Cancer Meeting in Tokushima 2017, 2017年8月. 佐藤康史 :
酸関連疾患における最近の話題∼逆流性食道炎の話題を中心に∼,
阿波吉野川支部・名西支部薬剤師会合同研修会, 2017年7月. 佐藤康史 :
「胃癌治療におけるNACの現状」内科の立場から見たNACの現状,
第2回北日本胃がん集学的治療研究会, 2017年3月.

特許: Yasushi Sato : Drug Carrier And Drug Carrier Kit For Inhibiting Fibrosis, 8173170. 佐藤康史 : 間葉系幹細胞の肝細胞への分化方法及び人工ヒト肝臓細胞, 特願PCT/JP2004/002440, 特許第WO2005024004 A1号. 佐藤康史 : 線維化抑制のための薬剤担体および薬物担体キット, 特許第2015111038号 (2015年). 佐藤康史 : (2000年9月), 特許第P2000284824号.
作品: 研究者総覧に該当データはありませんでした。
補助金・競争的資金: Exosomeエンジニアリングによる膵癌とその微小環境の改変を標的とする治療法の開発 (研究課題/領域番号: 23K27588 )
染色体不安定性に着目した大腸癌の抗癌剤耐性機序の解析 (研究課題/領域番号: 23K24321 )
鋸歯状ポリポーシス症候群の左側及び右側大腸癌の分子生物学的差異の解析 (研究課題/領域番号: 22K07986 )
プロテインアレイを用いた肝細胞癌に対するレンバチニブの新たなバイオマーカーの解明 (研究課題/領域番号: 21K07964 )
膵がん幹細胞を標的とした新たな光免疫療法の開発 (研究課題/領域番号: 20K08387 )
癌関連脂肪細胞の分泌型exosome解析による新たな膵癌進展機序の解明と臨床応用 (研究課題/領域番号: 19K08445 )
新規胃癌抗癌剤耐性因子としてのEGR1の意義 (研究課題/領域番号: 18K08006 )
JMJD2Aは進行胃癌においてエピジェネティック調節により薬剤感受性を制御する (研究課題/領域番号: 18K07942 )
FUTを標的とした進行大腸癌に対する抗EMT療法の開発 (研究課題/領域番号: 15K08971 )
Liquid biopsy及びDigitalPCRを用いた高感度胃癌診断法の開発 (研究課題/領域番号: 15K06857 )
胃癌のBH3 プロファイリングに基づく新規抗がん剤感受性試験の開発および予後予測 (研究課題/領域番号: 26460943 )
ＳＴｎ　ｓｙｎｔｈａｓｅを標的とした転移性胃癌に対する新規治療法の開発 (研究課題/領域番号: 24590921 )
大腸癌特異的に抗がん剤を送達する新規システムの開発 (研究課題/領域番号: 21590818 )
特異的線維化療法によるスキルス胃癌の新規治療法の開発 (研究課題/領域番号: 20390211 )
VA-Liposome-siRNAHSP47を用いた抗線維化治療 (研究課題/領域番号: 20249044 )
癌随伴線維芽細胞を標的としたがん治療法の開発 (研究課題/領域番号: 20015038 )
クローン化ヒト間葉系幹細胞を用いたヒト肝細胞への分化能の解析と肝再生療法への応用 (研究課題/領域番号: 18590740 )
肝星細胞のコラーゲン特異シャペロンHSP47を標的とした新しい肝線維化抑制療法 (研究課題/領域番号: 17590664 )
複製可能アデノウイルス導入骨髄間葉系幹細胞による新しい消化器癌治療法の開発 (研究課題/領域番号: 15790355 )
悪性黒色腫に対するcalreticulin/TRP-2DNAワクチンの開発 (研究課題/領域番号: 14026043 )
研究者番号（80343383）による検索

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2024年12月20日更新

専門分野・研究分野: 消化器内科学 (Gastroenterology)
消化器内視鏡
臨床腫瘍学
所属学会・所属協会: 財団法人日本消化器病学会
社団法人日本消化器内視鏡学会
日本肝臓病学会
日本臨床腫瘍学会
日本癌治療学会
日本癌学会
日本胃癌学会
日本カプセル内視鏡学会
日本消化管学会
ASCO
ESMO
日本家族性大腸腺腫症研究会
日本消化器病学会附置研究会「消化管ポリポーシス研究会」
日本内科学会四国支部
大腸肛門病病学会
日本家族性腫瘍学会
委員歴・役員歴: 財団法人日本消化器病学会 (財団評議員 [2020年3月], 四国支部幹事 [2018年1月〜2020年12月])
社団法人日本消化器内視鏡学会 (学会評議員, 四国支部常任評議員 [2016年12月〜2018年2月])
日本肝臓病学会 (西部会評議員)
日本臨床腫瘍学会 (学会評議員)
日本癌学会 (評議員)
日本胃癌学会 (代議員)
日本カプセル内視鏡学会 (評議委員)
ASCO (American Society for Medical Oncology) ( [2000年1月])
ESMO(European Society for Medical Oncology)
日本家族性大腸腺腫症研究会 (世話人)
日本消化器病学会附置研究会「消化管ポリポーシス研究会」 (幹事)
日本内科学会四国支部 (評議員 [2017年5月〜2019年5月])
大腸肛門病病学会 ( [2021年5月])
受賞: 1997年, 札幌医大医師会学術賞
2003年, 浜名湖シンポジウム研究助成賞
2004年, 浜名湖シンポジウム最優秀賞
2007年, APASL Conference Best poster award (Asian Pacific Association for the Study of the Liver)
2007年, 浜名湖シンポジウム最優秀賞
2008年, OTSUKA Award 肝臓学会賞 (日本肝臓病学会)
2009年, 第103回日本消化器病学会奨励賞 (日本消化器病学会北海道支部)
2011年, 第49回日本癌治療学会優秀演題賞 (日本癌治療学会)
2013年, 第51回日本癌治療学会最優秀演題賞 (日本癌治療学会)
2013年, 第113回日本消化器病学会奨励賞 (日本消化器病学会北海道支部)
活動: 財団法人日本消化器病学会 (ネットワーク委員会 [2017年6月〜2019年3月])
日本癌サポーティブケア学会 (Oncology emergency部会ワーキング委員 [2017年7月〜2019年6月])
財団法人日本消化器病学会 (機関誌編集委員会 Clinical Journal of Gastroenterology [2018年6月〜2021年3月])
日本臨床腫瘍学会 (広報渉外委員会委員 [2019年7月〜2022年7月])
World Gastroenterology Organisation (train the trainer workshop certified attendee [2019年4月〜4月])
Cancers (Editorial Board [2020年9月])
財団法人日本消化器病学会 (機関誌編集委員会 Journal of Gastroenterology [2021年4月])

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Jグローバル最終確認日: 2024/12/21 01:21
氏名（漢字）: 佐藤康史
氏名（フリガナ）: サトウヤスシ
氏名（英字）: Yasushi Sato
所属機関: 徳島大学特任教授

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researchmap最終確認日: 2024/12/22 01:35
氏名（漢字）: 佐藤康史
氏名（フリガナ）: サトウヤスシ
氏名（英字）: Yasushi Sato
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登録日時: 2006/5/22 00:00
更新日時: 2024/12/19 04:24
アバター画像URI: https://researchmap.jp/read0083229/avatar.png
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所属ID: 0344001001
所属: 徳島大学
部署: 徳島大学大学院医歯薬学研究部地域消化器・総合内科学
職名: 特任教授
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研究者番号: 80343383

所属（現在）: 2024/4/1 : 徳島大学, 大学院医歯薬学研究部(医学域), 特任教授

所属（過去の研究課題 情報に基づく）*注記: 2018/4/1 – 2024/4/1 : 徳島大学, 大学院医歯薬学研究部(医学域), 特任教授
2016/4/1 – 2017/4/1 : 徳島大学, 大学院医歯薬学研究部(医学系), 特任教授
2007/4/1 – 2015/4/1 : 札幌医科大学, 医学部, 講師
2002/4/1 – 2006/4/1 : 札幌医科大学, 医学部, 助手

審査区分/研究分野

研究代表者

生物系 / 医歯薬学 / 内科系臨床医学 / 消化器内科学
生物系 / 総合生物 / 腫瘍学 / 腫瘍診断学
小区分53010:消化器内科学関連

研究代表者以外

生物系 / 医歯薬学 / 内科系臨床医学 / 消化器内科学
生物系
小区分53010:消化器内科学関連

キーワード

研究代表者

骨髄間葉系幹細胞 / 複製可能アデノウイルス / 腫瘍ターゲッティング / 癌 / 糖鎖 / 胃癌 / 転移 / STn抗原 / 肝繊維化 / HSP47 / siRNA / レチノール / 肝線維化 / コラーゲン / in vivo / HEPATIC FIBROSIS / retinol / 診断 / biomarker / Liquid biopsy / Liquid Biopsy / 膵臓癌 / 膵癌 / exosome / miRNA / 脂肪細胞 / 癌関連脂肪細胞

研究代表者以外

Calreticulin / TRP-2 / DNAワクチン / 悪性黒色腫 / 腫瘍拒絶抗原 / 抗原性 / 抗体 / CAF / DDS / targeting / 細胞標的治療 / がん随伴線維芽細胞 / 肝臓学 / 抗線維化 / HSP47 / siRNA / 抗線維 / 癌 / 線維化 / 内科 / スキルス胃癌 / 抗がん剤 / 治療 / 後線維化 / 抗癌剤感受性 / 胃癌 / BH3プロファイリング / 全生存期間 / 胃がん / 肝再生治療 / hMSC / 肝硬変 / liver / transdifferentiation / 糖鎖 / 大腸がん / 転移 / 薬剤感受性 / エピジェネティック調節 / バイオマーカー / 抗癌剤耐性 / 効果予測因子 / がん幹細胞 / 光免疫療法 / オルガノイド / マウスモデル / 光免疫治療 / 膵がん / 分子イメージング / レンバチニブ / 肝細胞癌 / プロテインアレイ / ソラフェニブ / SPS / 鋸歯状ポリポーシス症候群 / 大腸癌 / 染色体不安定性 / 全ゲノム解析 / 蛍光イメージング / patient-derived organoid / 蛍光タイムラップス観察

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佐藤 康史

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佐藤康史