研究者詳細 - 寺井　崇二

論文 - 寺井　崇二

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高齢者の術後再建腸管結石例に対するダブルバルーン内視鏡下ERCPの検討

林和直, 五十嵐聡, 寺井崇二

Gastroenterological Endoscopy 65 ( Suppl.2 ) 2022 - 2022 2023年10月

自律神経経路を基軸とする脂肪性肝疾患の脂質代謝制御機構の解明と治療薬探索

上村顕也, 大脇崇史, 寺井崇二

日本消化器病学会雑誌 120 ( 臨増大会 ) A452 - A452 2023年10月

脂肪性肝疾患の個別化医療に向けた提案 NAFLDの病態進展に関わるエフェクターを標的とした治療法の開発

上村顕也, 薛徹, 寺井崇二

肝臓 64 ( Suppl.3 ) A743 - A743 2023年10月

Similarity of oncogenic protein expression in KRASG12D gene delivery-based rat pancreatic cancer model to that of human pancreatic cancer. 国際誌

Yuto Tanaka, Kenya Kamimura, Osamu Shibata, Kohei Ogawa, Chiyumi Oda, Hiroyuki Abe, Satoshi Ikarashi, Kazunao Hayashi, Takeshi Yokoo, Toshifumi Wakai, Shuji Terai

Biochemical and biophysical research communications 673 29 - 35 2023年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: The development of effective therapies and biomarkers for pancreatic cancer is an unmet clinical need. To address this, we have developed an easy-to-use pancreatic cancer rat animal model via pancreas-targeted hydrodynamic gene delivery of human pancreatic cancer-related genes. Our study aimed to determine the molecular similarity between the pancreatic tumor in the rat model and human pancreatic cancer. METHODS: KRASG12D gene-expressing plasmid was delivered to the pancreas of wild type rats via pancreas-targeted hydrodynamic gene delivery as previously reported. Tissue samples were collected at 5 weeks after the first gene delivery. The tumors developed in the rats were assessed for the expression of oncogenic proteins that are involved in human pancreatic cancer development. RESULTS: The development of a tumor mimicking pancreatic ductal adenocarcinoma was confirmed. The expression levels of Cyclin D1, c-Jun, IL-33, and Zip4 proteins in the tumor were immunohistochemically assessed and the correlation of the proteins was confirmed. The expression pattern showed similarity to that of surgically resected human pancreatic cancer tissues. CONCLUSIONS: Our study findings showing a similar pattern of oncogenic protein expression in novel KRASG12D gene-induced rat pancreatic cancer model and human pancreatic cancer will be useful for establishing novel tumor markers and therapeutic options for pancreatic cancer.

DOI： 10.1016/j.bbrc.2023.06.057

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Development and validation of machine learning model for predicting treatment responders in patients with primary biliary cholangitis. 国際誌

Naruhiro Kimura, Kazuya Takahashi, Toru Setsu, Yusuke Horibata, Yusuke Kaneko, Haruka Miyazaki, Kohei Ogawa, Yuzo Kawata, Norihiro Sakai, Yusuke Watanabe, Hiroyuki Abe, Hiroteru Kamimura, Akira Sakamaki, Takeshi Yokoo, Kenya Kamimura, Atsunori Tsuchiya, Shuji Terai

Hepatology research : the official journal of the Japan Society of Hepatology 2023年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

AIMS: Ursodeoxycholic acid is the first-line treatment for primary biliary cholangitis, and treatment response is one of the factors predicting the outcome. To prescribe alternative therapies, clinicians might need additional information before deciphering the treatment response to ursodeoxycholic acid, contributing to a better patient prognosis. In this study, we developed and validated machine learning (ML) algorithms to predict treatment responses using pretreatment data. METHODS: This multicenter cohort study included collecting datasets from two data samples. Data 1 included 245 patients from 18 hospitals for ML development, and was divided into (i) training and (ii) development sets. Data 2 (iii: test set) included 51 patients from our hospital for validation. An extreme gradient boosted tree predicted the treatment response in the ML model. The area under the curve was used to evaluate the efficacy of the algorithm. RESULTS: Data 1 showed that patients complying with the Paris II treatment response had significantly lower serum alkaline phosphatase and total bilirubin levels than those who did not respond. Three factors, total bilirubin, total protein, and alanine aminotransferase levels were selected as essential variables for prediction. Data 2 showed that patients complying with the Paris II criteria had significantly high prothrombin time and low total bilirubin levels. The area under the curve of extreme gradient boosted tree was good for (ii) (0.811) and (iii) (0.856). CONCLUSIONS: We demonstrated the efficacy of ML in predicting the treatment response for patients with primary biliary cholangitis. Early identification of cases requiring additional treatment with our novel ML model may improve prognosis.

DOI： 10.1111/hepr.13966

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肝疾患に対する再生医療のNew normal New Normalへの提案肝硬変に対する線維化改善を目指したトランスレーショナルリサーチ

土屋淳紀, 渡邉雄介, 寺井崇二

肝臓 64 ( Suppl.2 ) A570 - A570 2023年9月

多職種の肝炎医療コーディネーターとの連携による,院内におけるC型肝炎患者の拾い上げと紹介率向上の効果

荒生祥尚, 酒井規裕, 薛徹, 渡邉雄介, 木村成宏, 阿部寛幸, 坂牧僚, 上村博輝, 横尾健, 土屋淳紀, 上村顕也, 寺井崇二

肝臓 64 ( Suppl.2 ) A634 - A634 2023年9月

【肝疾患とサルコペニア】総論肝疾患とサルコペニア未来のリハビリテーション医療楽しくないと続かない

寺井崇二, 上村博輝

日本消化器病学会雑誌 120 ( 9 ) 701 - 708 2023年9月

消化器病に対する低侵襲治療切除不能肝内胆管癌に対して肝動脈化学塞栓療法(TACE)および重粒子線治療を行った1例

内山敦司, 上村博輝, 木村莉菓, 佐藤千紘, 木村究, 渡邉雄介, 高橋一也, 五十嵐聡, 寺井崇二

ENDOSCOPIC FORUM for digestive disease 39 ( 1 ) 37 - 37 2023年9月

Repurposable Drugs for Immunotherapy and Strategies to Find Candidate Drugs. 国際誌

Norihiro Sakai, Kenya Kamimura, Shuji Terai

Pharmaceutics 15 ( 9 ) 2023年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

Conventional drug discovery involves significant steps, time, and expenses; therefore, novel methods for drug discovery remain unmet, particularly for patients with intractable diseases. For this purpose, the drug repurposing method has been recently used to search for new therapeutic agents. Repurposed drugs are mostly previously approved drugs, which were carefully tested for their efficacy for other diseases and had their safety for the human body confirmed following careful pre-clinical trials, clinical trials, and post-marketing surveillance. Therefore, using these approved drugs for other diseases that cannot be treated using conventional therapeutic methods could save time and economic costs for testing their clinical applicability. In this review, we have summarized the methods for identifying repurposable drugs focusing on immunotherapy.

DOI： 10.3390/pharmaceutics15092190

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【ここまで進んだ肝硬変診療】肝硬変症の次世代治療の開発抗線維化治療と肝再生療法

寺井崇二, 土屋淳紀, 渡邊雄介, 阿部寛幸

臨床消化器内科 38 ( 10 ) 1329 - 1333 2023年8月

【ここまで進んだ肝硬変診療】肝硬変症の次世代治療の開発抗線維化治療と肝再生療法

寺井崇二, 土屋淳紀, 渡邊雄介, 阿部寛幸

臨床消化器内科 38 ( 10 ) 1329 - 1333 2023年8月

Correction: Medaka as a model for human nonalcoholic steatohepatitis. 国際誌

Toshihiko Matsumoto, Shuji Terai, Toshiyuki Oishi, Shinya Kuwashiro, Koichi Fujisawa, Naoki Yamamoto, Yusuke Fujita, Yoshihiko Hamamoto, Makoto Furutani-Seiki, Hiroshi Nishina, Isao Sakaida

Disease models & mechanisms 16 ( 7 ) 2023年7月

細胞および細胞外小胞で拓く創薬モダリティ細胞外小胞を用いた肝硬変に対する線維化改善、修復療法の開発

土屋淳紀, 寺井崇二

日本DDS学会学術集会プログラム予稿集 39回 101 - 101 2023年7月

BCL11B expression in hepatocellular carcinoma relates to chemosensitivity and clinical prognosis. 国際誌

Hiroyuki Abe, Kenya Kamimura, Shujiro Okuda, Yu Watanabe, Jun Inoue, Yutaka Aoyagi, Toshifumi Wakai, Ryo Kominami, Shuji Terai

Cancer medicine 12 ( 14 ) 15650 - 15663 2023年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

INTRODUCTION: B-cell lymphoma/leukemia 11B (BCL11B) is a subunit of SWI/SNF chromatin remodeling complexes and functions in cell cycle regulation and apoptosis upon DNA replication stress and damages via transcription. Many malignancies were reported to exhibit changes in BCL11B gene expression; however, no study has focused on the relationship between BCL11B and hepatocellular carcinoma, which potentially exhibits DNA replication stress and damages upon its oncogenesis. Thus, in this study, we examined the molecular characterization of BCL11B expression in hepatocellular carcinoma. METHODS AND RESULTS: The cumulative progression-free survival and overall survival were significantly longer in the clinical cases of BCL11B-negative hepatocellular carcinoma than BCL11B-positve cases. Microarray and real-time PCR analyses in hepatocellular carcinoma cell lines indicated a correlation between BCL11B and GATA6, a gene reported to be correlated with oncogenic activities and resistance to anthracycline, which is often used for hepatocellular carcinoma chemotherapy. Consequently, BCL11B-overexpressing cell lines exhibited resistance to anthracycline in cell growth assays and the resistance has been evidenced by the increased expression of BCL-xL in cell lines. The results were supported by the analyses of human HCC samples showing the correlation between BCL11B and GATA6 expressions. DISCUSSIONS AND CONCLUSION: Our results indicated that overexpression of BCL11B amplifies GATA6 expression in hepatocellular carcinoma in vitro and in vivo that leads to anti-apoptotic signal activation, and induces resistance to chemotherapy, which influenced the postoperative prognosis.

DOI： 10.1002/cam4.6167

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Portal venous gas caused by barium swallow examination: An extremely rare clinical finding. 国際誌

Takuya Wakabayashi, Kentaro Tominaga, Akira Sakamaki, Shuji Terai

Clinical case reports 11 ( 7 ) e7480 2023年7月

記述言語：英語

We found an extremely rare case of PVG after a barium swallow examination. This may be related to vulnerable intestinal mucosa in the patient undergoing prednisolone treatment. Conservative therapy should be considered for patients with PVG without bowel ischemia or perforation. Caution should be exercised during barium examination undergoing prednisolone treatment.

DOI： 10.1002/ccr3.7480

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細胞および細胞外小胞で拓く創薬モダリティ細胞外小胞を用いた肝硬変に対する線維化改善、修復療法の開発

土屋淳紀, 寺井崇二

日本DDS学会学術集会プログラム予稿集 39回 101 - 101 2023年7月

エンドトキシン吸着療法を行い救命し得た重症胆道感染症の2例

齋藤征爾, 坂田純, 滝沢一泰, 三浦宏平, 石川博補, 廣瀬雄己, 安藤拓也, 安部舜, 宗岡悠介, 田島陽介, 市川寛, 島田能史, 阿部寛幸, 小川光平, 寺井崇二, 若井俊文

新潟医学会雑誌 137 ( 7 ) 243 - 248 2023年7月

エンドトキシン吸着療法を行い救命し得た重症胆道感染症の2例

新潟医学会雑誌 137 ( 7 ) 243 - 248 2023年7月

Machine learning prediction model for treatment responders in patients with primary biliary cholangitis. 国際誌

Naruhiro Kimura, Kazuya Takahashi, Toru Setsu, Shu Goto, Suguru Miida, Nobutaka Takeda, Yuichi Kojima, Yoshihisa Arao, Kazunao Hayashi, Norihiro Sakai, Yusuke Watanabe, Hiroyuki Abe, Hiroteru Kamimura, Akira Sakamaki, Takeshi Yokoo, Kenya Kamimura, Atsunori Tsuchiya, Shuji Terai

JGH open : an open access journal of gastroenterology and hepatology 7 ( 6 ) 431 - 438 2023年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND AND AIM: Treatment response to ursodeoxycholic acid may predict the prognosis of patients with primary biliary cholangitis (PBC). Recent studies have suggested the benefits of using machine learning (ML) to forecast complex medical predictions. We aimed to predict treatment response in patients with PBC using ML and pretreatment data. METHODS: We conducted a single-center retrospective study and collected data from 194 patients with PBC who were followed up for at least 12 months after treatment initiation. Patient data were analyzed with five ML models, namely random forest, extreme gradient boosting (XGB), decision tree, naïve Bayes, or logistic regression, to predict treatment response using the Paris II criteria. The established models were assessed using an out-of-sample validation. The area under the curve (AUC) was used to evaluate the efficacy of each algorithm. Overall survival and liver-related deaths were analyzed using Kaplan-Meier analysis. RESULTS: Compared to logistic regression (AUC = 0.595, P = 0.0219, 0.031 models), ML analyses showed significantly high AUC in the random forest (AUC = 0.84) and XGB (AUC = 0.83) models; however, the AUC was not significantly high for decision tree (AUC = 0.633) or naïve Bayes (AUC = 0.584) models. Kaplan-Meier analysis showed significantly improved prognoses in patients predicted to achieve the Paris II criteria by XGB (log-rank = 0.005 and 0.007). CONCLUSION: ML algorithms could improve treatment response prediction using pretreatment data, which could lead to better prognoses. In addition, the ML model using XGB could predict the prognosis of patients before treatment initiation.

DOI： 10.1002/jgh3.12915

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