研究者詳細 - 大塚　基之

論文 - 大塚　基之

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Helicobacter pylori除菌により寛解し、長期間経過後に再発した胃MALTリンパ腫の一例

稲生祥子, 岩室雅也, 平田翔一郎, 平井亮佑, 倉岡紗樹子, 小橋真由, 岡上昇太郎, 里見拓也, 松枝克典, 濱田健太, 河野吉泰, 川野誠司, 河原祥朗, 大塚基之

日本消化器病学会中国支部例会プログラム・抄録集 119回 71 - 71 2023年6月

免疫関連有害事象(irAE:immune-related adverse events)による胃炎の5例

岩室雅也, 田中健大, 平田翔一郎, 河野吉泰, 川野誠司, 河原祥朗, 大塚基之

日本消化器病学会中国支部例会プログラム・抄録集 119回 70 - 70 2023年6月

内反性増殖を示した十二指腸腺癌に対してUnderwater EMRにて切除し得た1例

松枝克典, 川野誠司, 平田翔一郎, 岡上昇太郎, 里見拓也, 稲生祥子, 濱田健太, 河野吉泰, 岩室雅也, 河原祥朗, 田中健大, 大塚基之

日本消化器内視鏡学会中国支部例会 130回 76 - 76 2023年6月

肝生検により診断された播種性bacillus Calmette-Guerin(BCG)症の1例

伊木道子, 竹内康人, 須江真彦, 三宅望, 足立卓哉, 和田望, 大西秀樹, 白羽秀則, 高木章乃夫, 大塚基之

日本消化器病学会中国支部例会プログラム・抄録集 119回 62 - 62 2023年6月

血流豊富な粘膜下腫瘍の形態を呈した上行結腸血管周囲類上皮細胞腫の1例

青山祐樹, 井口俊博, 平岡佐規子, 豊澤惇希, 竹井健介, 井川翔子, 山崎泰史, 衣笠秀明, 高原政宏, 庄司良平, 近藤喜太, 柳井広之, 大塚基之

日本消化器内視鏡学会中国支部例会 130回 81 - 81 2023年6月

免疫関連有害事象(irAE:immune-related adverse events)による胃炎の5例

岩室雅也, 田中健大, 平田翔一郎, 河野吉泰, 川野誠司, 河原祥朗, 大塚基之

日本消化器病学会中国支部例会プログラム・抄録集 119回 70 - 70 2023年6月

Collagenous Colitis in a Patient With Gastric Cancer Who Underwent Chemotherapy. 査読国際誌

Masaya Iwamuro, Takehiro Tanaka, Shunsuke Kagawa, Shoko Inoo, Motoyuki Otsuka

Cureus 15 ( 5 ) e39466 2023年5月

記述言語：英語

Herein, we present a case of collagenous colitis in a patient who underwent chemotherapy for gastric cancer, comprising five cycles of S-1 plus oxaliplatin and trastuzumab, followed by five cycles of paclitaxel and ramucirumab and seven cycles of nivolumab. The subsequent initiation of trastuzumab deruxtecan chemotherapy led to the development of grade 3 diarrhea after the second cycle of treatment. Collagenous colitis was diagnosed via colonoscopy and biopsy. The patient's diarrhea improved following the cessation of lansoprazole. This case highlights the importance of considering collagenous colitis as a differential diagnosis, in addition to chemotherapy-induced colitis and immune-related adverse event (irAE) colitis, in patients with similar clinical presentations.

DOI： 10.7759/cureus.39466

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選択的胆管seekingのためのデバイス選択

小幡泰介, 内田大輔, 加藤博也, 佐藤亮介, 松三明宏, 宮本和也, 森本光作, 寺澤裕之, 藤井佑樹, 山崎辰洋, 松本和幸, 堀口繁, 堤康一郎, 大塚基之

Gastroenterological Endoscopy 65 ( Suppl.1 ) 971 - 971 2023年4月

選択的胆管seekingのためのデバイス選択

小幡泰介, 内田大輔, 加藤博也, 佐藤亮介, 松三明宏, 宮本和也, 森本光作, 寺澤裕之, 藤井佑樹, 山崎辰洋, 松本和幸, 堀口繁, 堤康一郎, 大塚基之

Gastroenterological Endoscopy 65 ( Suppl.1 ) 971 - 971 2023年4月

EUS-HGSにおけるダブルガイドワイヤー法の有用性

松三明宏, 藤井佑樹, 小幡泰介, 佐藤亮介, 織田崇志, 菊池達也, 宮本和也, 森本光作, 寺澤裕之, 山崎辰洋, 内田大輔, 松本和幸, 堀口繁, 堤康一郎, 加藤博也, 大塚基之

日本消化器病学会雑誌 120 ( 臨増総会 ) A321 - A321 2023年3月

後期高齢者におけるIPMNの治療移行割合についての検討

宮本和也, 松本和幸, 小幡泰介, 佐藤亮介, 織田崇志, 菊池達也, 松三明宏, 森本光作, 寺澤裕之, 藤井佑樹, 山崎辰洋, 内田大輔, 堀口繁, 堤康一郎, 加藤博也, 大塚基之

日本消化器病学会雑誌 120 ( 臨増総会 ) A378 - A378 2023年3月

胆嚢オルガノイドを用いた発癌モデルより同定したmiR-34a-5p補充による胆嚢癌治療の開発

織田崇志, 堤康一郎, 小幡泰介, 菊池達也, 松三明宏, 宮本和也, 森本光作, 寺澤裕之, 藤井佑樹, 山崎辰洋, 赤穂宗一郎, 内田大輔, 松本和幸, 堀口繁, 加藤博也, 大塚基之

日本消化器病学会雑誌 120 ( 臨増総会 ) A328 - A328 2023年3月

Optimal liver drainage rate for survival in patients with unresectable malignant hilar biliary obstruction using 3D-image volume analyzer. 国際誌

Kosaku Morimoto, Kazuyuki Matsumoto, Taisuke Obata, Takashi Oda, Kazuya Miyamoto, Akihiro Matsumi, Hiroyuki Terasawa, Yuki Fujii, Tatsuhiro Yamazaki, Shigeru Horiguchi, Koichiro Tsutsumi, Hironari Kato, Motoyuki Otsuka

Therapeutic advances in gastroenterology 16 17562848231206980 - 17562848231206980 2023年

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Drainage exceeding 50% of total liver volume is a beneficial prognostic factor in patients with unresectable malignant hilar biliary obstruction (UMHBO). However, it is unclear what threshold percentage of total liver volume drained ('liver drainage rate') significantly improves survival in patients with UMHBO who received systemic chemotherapy. OBJECTIVES: We aimed to assess the optimal liver drainage rate that improves survival in patients with UMHBO receiving chemotherapy using a three-dimensional (3D)-image volume analyzer. DESIGN: This study was a single-center retrospective cohort study. METHODS: Data from 90 patients with UMHBO who received chemotherapy after endoscopic biliary drainage using metal stents at Okayama University Hospital from January 2003 to December 2020 were reviewed. The liver drainage rate was calculated by dividing the drained liver volume by the total liver volume using a 3D-image volume analyzer. The primary endpoint was overall survival by liver drainage rate. The secondary endpoints were time to recurrent biliary obstruction (TRBO) and prognostic factors. RESULTS: The median total liver volume was 1172 (range: 673-2032) mL, and the median liver drainage rate was 83% (range: 50-100). Overall survival was 376 (95% CI: 271-450) days, and patients with >80% drainage (n = 67) had significantly longer survival than those with <80% drainage (n = 23) (450 days versus 224 days, p = 0.0033, log-rank test). TRBO was 201 (95% CI: 155-327) days and did not differ significantly by liver drainage rate. Multivariate Cox proportional hazards regression analysis revealed >80% liver drainage [hazard ratio (HR): 0.35, 95% CI: 0.20-0.62, p = 0.0003] and hilar cholangiocarcinoma (HR: 0.30, 95% CI: 0.17-0.50, p < 0.0001) as significant prognostic factors. CONCLUSION: In patients with UMHBO scheduled for chemotherapy, >80% drainage is associated with improved survival. Further prospective multicenter studies are needed to verify the results of this study. TRAIL REGISTRATION: Okayama University Hospital, IRB number: 2108-011.

DOI： 10.1177/17562848231206980

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Smaller extracellular vesicles are released from pancreatic cancer cells by the alteration of the lipid composition under low glucose conditions. 査読国際誌

Chikako Shibata, Motoyuki Otsuka, Takahiro Seimiya, Kazunaga Ishigaki, Yu Miyakawa, Takahiro Kishikawa, Mitsuhiro Fujishiro

Biochemical and biophysical research communications 637 314 - 321 2022年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

Extracellular vesicles (EVs) released from cells into the blood facilitate intercellular communication and serve as new biomarkers to understand the pathophysiology of several conditions. Although the importance of the cargo inside EVs has been extensively studied, the sizes of EVs that vary with different types of cancers are relatively poorly explored. Here, we show that pancreatic cancer cell-derived EVs are significantly smaller than non-cancer cell-derived EVs. The smaller size distribution of these EVs was confirmed by specifically isolating and examining tumor-derived EVs from the heterogeneous EV population isolated from the sera of patients with pancreatic ductal adenocarcinoma. In vitro analyses mimicking tumor microenvironment conditions revealed that low glucose conditions reduced the size distribution and increased the level of unsaturated fatty acids in the tumor-derived EVs. Because the lipid composition defines the fluidity of the membrane, the results suggest that the alterations in the size of EVs could be due to the alteration of the fluidity and stability of the membrane covering the EVs. Furthermore, the uptake of smaller EVs by recipient cells was increased, which may lead to enhanced functional results. These results provide fundamental insights into the factors defining the size of EVs, which may be important for developing cancer screening methods and understanding cancer-related pathophysiology.

DOI： 10.1016/j.bbrc.2022.11.040

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HNF1B-driven three-dimensional chromatin structure for molecular classification in pancreatic cancers. 査読国際誌

Hiroyuki Kato, Keisuke Tateishi, Dosuke Iwadate, Keisuke Yamamoto, Hiroaki Fujiwara, Takuma Nakatsuka, Yotaro Kudo, Yoku Hayakawa, Hideaki Ijichi, Motoyuki Otsuka, Takahiro Kishikawa, Ryota Takahashi, Koji Miyabayashi, Yousuke Nakai, Yoshihiro Hirata, Atsushi Toyoda, Shinichi Morishita, Mitsuhiro Fujishiro

Cancer science 114 ( 4 ) 1672 - 1685 2022年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

The molecular subtypes of pancreatic cancer (PC), either classical/progenitor-like or basal/squamous-like, are currently a major topic of research because of their direct association with clinical outcomes. Some transcription factors (TFs) have been reported to be associated with these subtypes. However, the mechanisms by which these molecular signatures of PCs are established remain unknown. Epigenetic regulatory processes, supported by dynamic changes in the chromatin structure, are essential for transcriptional profiles. Previously, we reported the importance of open chromatin profiles in the biological features and transcriptional status of PCs. Here, we aimed to analyze the relationships between three-dimensional (3D) genome structures and the molecular subtypes of human PCs using Hi-C analysis. We observed a correlation of the specific elements of 3D genome modules, including compartments, topologically associating domains, and enhancer-promoter loops, with the expression of related genes. We focused on HNF1B, a TF that is implicated in the progenitor subtype. Forced expression of HNF1B in squamous-type PC organoids induced the upregulation and downregulation of genes associated with progenitor and squamous subtypes, respectively. Long-range genomic interactions induced by HNF1B were accompanied by compartment modulation and H3K27ac redistribution. We also found that these HNF1B-induced changes in subtype-related gene expression required an intrinsically disordered region, suggesting a possible involvement of phase separation in compartment modulation. Thus, mapping of 3D structural changes induced by TFs, such as HNF1B, may become a useful resource for further understanding the molecular features of PCs.

DOI： 10.1111/cas.15690

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The RNA-Binding Protein ELAVL1 Regulates Hepatitis B Virus Replication and Growth of Hepatocellular Carcinoma Cells. 査読国際誌

Hiroaki Kanzaki, Tetsuhiro Chiba, Tatsuya Kaneko, Junjie Ao, Motoyasu Kan, Ryosuke Muroyama, Shingo Nakamoto, Tatsuo Kanda, Hitoshi Maruyama, Jun Kato, Yoh Zen, Ai Kotani, Kazuma Sekiba, Motoyuki Otsuka, Masayuki Ohtsuka, Naoya Kato

International journal of molecular sciences 23 ( 14 ) 2022年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

Previous RNA immunoprecipitation followed by proteomic approaches successfully demonstrated that Embryonic Lethal, Abnormal Vision, Drosophila-Like 1 (ELAVL1) interacts with hepatitis B virus (HBV)-derived RNAs. Although ELAVL family proteins stabilize AU-rich element (ARE)-containing mRNAs, their role in HBV transcription remains unclear. This study conducted loss-of-function assays of ELAVL1 for inducible HBV-replicating HepAD38 cells and HBx-overexpressed HepG2 cells. In addition, clinicopathological analyses in primary hepatocellular carcinoma (HCC) surgical samples were also conducted. Lentivirus-mediated short hairpin RNA knockdown of ELAVL1 resulted in a decrease in both viral RNA transcription and production of viral proteins, including HBs and HBx, probably due to RNA stabilization by ELAVL1. Cell growth of HepAD38 cells was more significantly impaired in ELAVL1-knockdown than those in the control group, with or without HBV replication, indicating that ELAVL1 is involved in proliferation by factors other than HBV-derived RNAs. Immunohistochemical analyses of 77 paired HCC surgical specimens demonstrated that diffuse ELAVL1 expression was detected more frequently in HCC tissues (61.0%) than in non-tumor tissues (27.3%). In addition, the abundant expression of ELAVL1 tended to affect postoperative recurrence in HBV-related HCC patients. In conclusion, ELAVL1 contributes not only to HBV replication but also to HCC cell growth. It may be a potent therapeutic target for HBV-related HCC treatment.

DOI： 10.3390/ijms23147878

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Hepatitis B virus-associated hepatocellular carcinoma with Smc5/6 complex deficiency is susceptible to PARP inhibitors. 査読国際誌

Kazuyoshi Funato, Motoyuki Otsuka, Kazuma Sekiba, Yu Miyakawa, Takahiro Seimiya, Chikako Shibata, Takahiro Kishikawa, Mitsuhiro Fujishiro

Biochemical and biophysical research communications 607 89 - 95 2022年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

DNA repair processes represent attractive synthetic lethal targets because many cancers exhibit impaired DNA repair pathways, which leads to dependence on specific repair proteins. The finding that poly (ADP-ribose) polymerase (PARP)-1 inhibitors are highly effective against cancers with deficient homologous recombination highlights the potential of this approach. In hepatitis B viral (HBV) infection, degradation of the structural maintenance of the chromosome 5/6 (Smc5/6) complex, which plays a key role in repairing double-stranded DNA breaks by homologous recombination, is induced by HBV regulatory protein X (HBx). Here, we hypothesized that a deficiency in the Smc5/6 complex in HBV-associated hepatocellular carcinoma (HCC) increases susceptibility to PARP inhibitors via a deficiency in homologous recombination. We confirmed impaired double-stranded DNA break repair in HBx-expressing HCC cells using a sensitive reporter to monitor homologous recombination. Treatment with a PARP inhibitor was significantly more effective against HBx-expressing HCC cells, and overexpression of Smc5/6 prevented these effects. Overall, our results suggest that homologous recombination deficiency in HBV-associated HCC leads to increased susceptibility to PARP inhibitors.

DOI： 10.1016/j.bbrc.2022.03.137

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Roles of circular RNAs in the pathogenesis and treatment of pancreatic cancer. 査読国際誌

Takahiro Seimiya, Motoyuki Otsuka, Mitsuhiro Fujishiro

Frontiers in cell and developmental biology 10 1023332 - 1023332 2022年

記述言語：英語掲載種別：研究論文（学術雑誌）

Circular RNAs are single-stranded RNAs with a covalently closed structure formed by the process of back-splicing. Aberrant expression of circular RNAs contributes to the pathogenesis of a wide range of cancers. Pancreatic cancer is one of the most lethal cancers due to diagnostic difficulties and limited therapeutic options. Circular RNAs are emerging as novel diagnostic biomarkers and therapeutic targets for pancreatic cancer. Moreover, recent advances in the therapeutic application of engineered circular RNAs have provided a promising approach to overcoming pancreatic cancer. This review discusses the roles of circular RNAs in the pathogenesis of pancreatic cancer and in potential treatment applications and their usefulness as diagnostic biomarkers.

DOI： 10.3389/fcell.2022.1023332

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Evidence-based clinical practice guidelines for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis 2020. 国際誌

Motoyuki Otsuka

Hepatology research : the official journal of the Japan Society of Hepatology 51 ( 10 ) 1013 - 1025 2021年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

Nonalcoholic fatty liver disease (NAFLD) has become a serious public health issue not only in Western countries but also in Japan. Within the wide spectrum of NAFLD, nonalcoholic steatohepatitis (NASH) is a progressive form of disease that often develops into liver cirrhosis and increases the risk of hepatocellular carcinoma (HCC). While a definite diagnosis of NASH requires liver biopsy to confirm the presence of hepatocyte ballooning, hepatic fibrosis is the most important prognostic factor in NAFLD. With so many NAFLD patients, it is essential to have an effective screening method for NAFLD with hepatic fibrosis. As HCC with non-viral liver disease has increased markedly in Japan, effective screening and surveillance of HCC are also urgently needed. The most common death etiology in NAFLD patients is cardiovascular disease event. Gastroenterologists must, therefore, pay close attention to CVD when examining NAFLD patients. In the updated guidelines, we propose screening and follow-up methods for hepatic fibrosis, HCC, and CVD in NAFLD patients. Several drug trials are ongoing for NAFLD/NASH therapy, however, there is currently no specific drug therapy for NAFLD/NASH. In addition to vitamin E and thiazolidinedione derivatives, recent trials have focused on sodium glucose co-transporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) analogues, and effective therapies are expected to be developed. These practical guidelines for NAFLD/NASH were established by the Japanese Society of Gastroenterology in conjunction with the Japan Society of Hepatology. Clinical evidence reported internationally between 1983 and October 2018 was collected, and each clinical and background question was evaluated using the Grades of Recommendation Assessment, Development and Evaluation (GRADE) system. This English summary pro- vides the core essentials of these clinical practice guidelines, which include the definition and concept, screening systems for hepatic fibrosis, HCC and CVD, and current therapies for NAFLD/NASH in Japan.

DOI： 10.1111/hepr.13688

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Evidence-based clinical practice guidelines for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis 2020.

Motoyuki Otsuka

Journal of gastroenterology 56 ( 11 ) 951 - 963 2021年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

Nonalcoholic fatty liver disease (NAFLD) has become a serious public health issue not only in Western countries but also in Japan. Within the wide spectrum of NAFLD, nonalcoholic steatohepatitis (NASH) is a progressive form of disease that often develops into liver cirrhosis and increases the risk of hepatocellular carcinoma (HCC). While a definite diagnosis of NASH requires liver biopsy to confirm the presence of hepatocyte ballooning, hepatic fibrosis is the most important prognostic factor in NAFLD. With so many NAFLD patients, it is essential to have an effective screening method for NAFLD with hepatic fibrosis. As HCC with non-viral liver disease has increased markedly in Japan, effective screening and surveillance of HCC are also urgently needed. The most common death etiology in NAFLD patients is cardiovascular disease (CVD) event. Gastroenterologists must, therefore, pay close attention to CVD when examining NAFLD patients. In the updated guidelines, we propose screening and follow-up methods for hepatic fibrosis, HCC, and CVD in NAFLD patients. Several drug trials are ongoing for NAFLD/NASH therapy, however, there is currently no specific drug therapy for NAFLD/NASH. In addition to vitamin E and thiazolidinedione derivatives, recent trials have focused on sodium glucose co-transporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) analogues, and effective therapies are expected to be developed. These practical guidelines for NAFLD/NASH were established by the Japanese Society of Gastroenterology in conjunction with the Japan Society of Hepatology. Clinical evidence reported internationally between 1983 and October 2018 was collected, and each clinical and background question was evaluated using the Grades of Recommendation Assessment, Development and Evaluation (GRADE) system. This English summary provides the core essentials of these clinical practice guidelines, which include the definition and concept, screening systems for hepatic fibrosis, HCC and CVD, and current therapies for NAFLD/NASH in Japan.

DOI： 10.1007/s00535-021-01796-x

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