Degree 【 display / non-display 】

Degree 【 display / non-display 】

• 京都大学   医学博士

Research Areas 【 display / non-display 】

Research Areas 【 display / non-display 】

• Life sciences   Gastroenterology   inflammatory bowel disease

Affiliation 【 display / non-display 】

Affiliation 【 display / non-display 】

• Sapporo Medical University   消化器内科学講座   教授  

Research Interests 【 display / non-display 】

Research Interests 【 display / non-display 】

• mucosal immunology

• cytokine

• Macrophage

• intestinal epithelial cells

Papers 【 display / non-display 】

Papers 【 display / non-display 】

• A rare case of resection of a mucinous cystic neoplasm originating from the extrahepatic bile duct with cholangioscopic imaging.

  Yoshiharu Masaki, Yujiro Kawakami, Keisuke Ishigami, Ayako Murota, Masahiro Shitani, Kazuharu Kukita, Yasutoshi Kimura, Keiko Segawa, Tadashi Hasegawa, Hiroshi Nakase

  DEN open   4 ( 1 ) e349  2024.04  [International journal]

  　View Summary

  A 29-year-old woman was admitted to our hospital for examination of obstructive jaundice and an extrahepatic bile duct lesion. Contrast-enhanced computed tomography revealed a 20 mm cystic lesion with a thin external capsule in the common hepatic duct. Cholangioscopy revealed translucent oval masses with capillary vessels attached to the bile duct walls. The surface was mostly smooth yet partially irregular with redness, suggesting that the masses were epithelial neoplasms. Histological findings of cholangioscopy-guided targeted biopsies of the mass showed subepithelial spindle cell proliferation with no atypical epithelium. The patient underwent an extrahepatic bile duct resection to confirm the pathological diagnosis. Immunohistochemistry of surgical specimens revealed that the spindle cells were positive for estrogen and progesterone receptors. Finally, the cystic lesion with ovarian-like stroma was diagnosed as a mucinous cystic neoplasm with low-grade intraepithelial neoplasia. This is the first report of cholangioscopic imaging of a biliary mucinous cyctic neoplasm. Cholangioscopic imaging can be helpful in the differential diagnosis of biliary neoplasms and in the determination of treatment strategies.

  DOI PubMed

• Genomic analysis of an aggressive hepatic leiomyosarcoma case following treatment for hepatocellular carcinoma.

  Yuto Numata, Noriyuki Akutsu, Masashi Idogawa, Kohei Wagatsuma, Yasunao Numata, Keisuike Ishigami, Tomoya Nakamura, Takehiro Hirano, Yujiro Kawakami, Yoshiharu Masaki, Ayako Murota, Shigeru Sasaki, Hiroshi Nakase

  Hepatology research : the official journal of the Japan Society of Hepatology    2024.03  [International journal]

  　View Summary

  A 70-year-old man undergoing treatment for immunoglobulin G4-related disease developed a liver mass on computed tomography during routine imaging examination. The tumor was located in the hepatic S1/4 region, was 38 mm in size, and showed arterial enhancement on dynamic contrast-enhanced computed tomography. We performed a liver biopsy and diagnosed moderately differentiated hepatocellular carcinoma. The patient underwent proton beam therapy. The tumor remained unchanged but enlarged after 4 years. The patient was diagnosed with hepatocellular carcinoma recurrence and received hepatic arterial chemoembolization. However, 1 year later, the patient developed jaundice, and the liver tumor grew in size. Unfortunately, the patient passed away. Autopsy revealed that the tumor consisted of spindle-shaped cells exhibiting nuclear atypia and a fission pattern and tested positive for α-smooth muscle actin and vimentin. No hepatocellular carcinoma components were observed, and the patient was pathologically diagnosed with hepatic leiomyosarcoma. Next-generation sequencing revealed somatic mutations in CACNA2D4, CTNNB1, DOCK5, IPO8, MTMR1, PABPC5, SEMA6D, and ZFP36L1. Based on the genetic mutation, sarcomatoid hepatocarcinoma was the most likely pathogenesis in this case. This mutation is indicative of the transition from sarcomatoid hepatocarcinoma to hepatic leiomyosarcoma.

  DOI PubMed

• Downregulation of SMOC1 is associated with progression of colorectal traditional serrated adenomas.

  Hironori Aoki, Akira Takasawa, Eiichiro Yamamoto, Takeshi Niinuma, Hiro-O Yamano, Taku Harada, Toshiyuki Kubo, Akira Yorozu, Hiroshi Kitajima, Kazuya Ishiguro, Masahiro Kai, Akio Katanuma, Toshiya Shinohara, Hiroshi Nakase, Tamotsu Sugai, Makoto Osanai, Hiromu Suzuki

  BMC gastroenterology   24 ( 1 ) 91 - 91  2024.03  [International journal]

  　View Summary

  BACKGROUND: Aberrant DNA methylation is prevalent in colorectal serrated lesions. We previously reported that the CpG island of SMOC1 is frequently methylated in traditional serrated adenomas (TSAs) and colorectal cancers (CRCs) but is rarely methylated in sessile serrated lesions (SSLs). In the present study, we aimed to further characterize the expression of SMOC1 in early colorectal lesions. METHODS: SMOC1 expression was analyzed immunohistochemically in a series of colorectal tumors (n = 199) and adjacent normal colonic tissues (n = 112). RESULTS: SMOC1 was abundantly expressed in normal colon and SSLs while it was significantly downregulated in TSAs, advanced adenomas and cancers. Mean immunohistochemistry scores were as follows: normal colon, 24.2; hyperplastic polyp (HP), 18.9; SSL, 23.8; SSL with dysplasia (SSLD)/SSL with early invasive cancer (EIC), 15.8; TSA, 5.4; TSA with high grade dysplasia (HGD)/EIC, 4.7; non-advanced adenoma, 21.4; advanced adenoma, 11.9; EIC, 10.9. Higher levels SMOC1 expression correlated positively with proximal colon locations and flat tumoral morphology, reflecting its abundant expression in SSLs. Among TSAs that contained both flat and protruding components, levels of SMOC1 expression were significantly lower in the protruding components. CONCLUSION: Our results suggest that reduced expression of SMOC1 is associated with progression of TSAs and conventional adenomas and that SMOC1 expression may be a biomarker for diagnosis of serrated lesions and risk prediction in colorectal tumors.

  DOI PubMed

• The frequency and pathogenicity of BRCA1 and BRCA2 variants in the general Japanese population.

  Masashi Idogawa, Tasuku Mariya, Yumi Tanaka, Tsuyoshi Saito, Hiroshi Nakase, Takashi Tokino, Akihiro Sakurai

  Journal of human genetics    2024.02  [International journal]

  　View Summary

  Hereditary breast and ovarian cancer syndrome (HBOC) resulting from pathogenic variants of BRCA1 or BRCA2 is the most common and well-documented hereditary tumor. Although founder variants have been identified in population-based surveys in various countries, the types of variants are not uniform across races and regions. Recently, the Tohoku Medical Megabank Organization (ToMMo) released whole-genome sequence data including approximately 54,000 individuals from the general population of the Tohoku area in Japan. We analyzed these data and comprehensively identified the prevalence of BRCA1/2 pathogenic and truncating variants. We believe that an accurate understanding of the unique distribution and characteristics of pathogenic BRCA1/2 variants in Japan through this analysis will enable better surveillance and intervention for HBOC patients, not only in Japan but also worldwide.

  DOI PubMed

• Maintenance steroid therapy is associated with decreased risk of malignancy and better prognosis of patients with autoimmune pancreatitis: A multicenter cohort study in Japan

  Tetsuya Takikawa, Kazuhiro Kikuta, Takanori Sano, Tsukasa Ikeura, Nao Fujimori, Takeji Umemura, Itaru Naitoh, Hiroshi Nakase, Hiroyuki Isayama, Atsushi Kanno, Ken Kamata, Yuzo Kodama, Dai Inoue, Akio Ido, Toshiharu Ueki, Hiroshi Seno, Hiroaki Yasuda, Eisuke Iwasaki, Takayoshi Nishino, Kensuke Kubota, Toshihiko Arizumi, Atsushi Tanaka, Kazushige Uchida, Ryotaro Matsumoto, Shin Hamada, Seiji Nakamura, Kazuichi Okazaki, Yoshifumi Takeyama, Atsushi Masamune, Shinji Nakayama, Akira Nakamura, Yoshiharu Masaki, Mako Ushio, Tomohiro Watanabe, Masahiro Tsujimae, Shiro Tanoue, Toru Maruo, Masahiro Shiokawa, Satoki Yamane, Atsuto Kayashima

  Pancreatology ( Elsevier BV )   2024.01

  DOI

display all >>

Books and Other Publications 【 display / non-display 】

Books and Other Publications 【 display / non-display 】

• 特集炎症性腸疾患診療の最前線 潰瘍性大腸炎の内科治療

  仲瀬 裕志, 吉野琢哉, 松浦 稔( Part： Contributor)

  日本医師会雑誌  2015

• D.消化管全般にわたるもの 膠原病の消化器病変

  仲瀬 裕志( Part： Contributor)

  南江堂.  2015

• 内科診療Q＆A －下部消化管

  仲瀬 裕志, 千葉 勉( Part： Contributor, 便秘の分類と治療)

  東京：六法出版社.  1997

Misc 【 display / non-display 】

Misc 【 display / non-display 】

• 座談会 膵臓がん克服のためにわれわれがなすべきこととは? : 現在,そして未来

  仲瀬 裕志, 潟沼 朗生, 正宗 淳, 福田 晃久

  消化器病学サイエンス = Science of gastroenterology / 「消化器病学サイエンス」編集委員会 編   6 ( 4 ) 205 - 214  2022.12

• SMOC1の大腸腫瘍診断マーカーとしての臨床的有用性の検討

  青木 敬則, 山本 英一郎, 高澤 啓, 新沼 猛, 山野 泰穂, 萬 顕, 北嶋 洋志, 甲斐 正広, 小山内 誠, 仲瀬 裕志, 菅井 有, 鈴木 拓

  日本癌学会総会記事 ( (一社)日本癌学会 )  80回   [P14 - 4]  2021.09

• ステロイド治療によって機能性消化管障害が改善したIgG4関連疾患の1例

  平野 雄大, 川上 裕次郎, 我妻 康平, 沼田 泰尚, 石上 敬介, 柾木 喜晴, 室田 文子, 本谷 雅代, 阿久津 典之, 佐々木 茂, 神田 真聡, 仲瀬 裕志

  日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集 ( 日本消化器病学会-北海道支部 )  129回・123回   33 - 33  2021.09

  J-GLOBAL

• 腫瘍生検組織を用いた次世代シークエンシングによりIDH1変異を同定した超高齢者Cholangiolocarcinomaの1例

  吉田幸成, 岩田徳和, 佐々木泰史, 石井良文, 安達靖代, 足立靖, 佐々木茂, 仲瀬裕志, 遠藤高夫

  日本消化器病学会雑誌(Web)   118  2021

  J-GLOBAL

• 難治性炎症性腸管障害に関する調査研究 炎症性腸疾患関連血栓症の全国調査および予防的抗血栓療法の有効性

  藤谷幹浩, 安藤勝祥, 稲場勇平, 野村好紀, 上野伸展, 盛一健太郎, 前本篤男, 蘆田知史, 田邊裕貴, 高後裕, 仲瀬裕志, 山田聡, 田中一之, 櫻井俊之, 猿田雅之, 八月朔日秀明, 穂苅量太, 岡昌平, 平岡佐規子, 加賀谷尚史, 田中敏宏, 福井寿朗, 鳥巣剛弘, 齋藤大祐, 久松理一, 長堀正和, 加藤真吾, 志賀永嗣, 角田洋一, 渡辺憲治, 中村志郎, 池内浩基, 林亮平, 田中信治, 虻川大樹, 佐々木誠人, 飯塚政弘, 飯島英樹, 水島恒和, 小林清典, 小林拓, 内山和彦, 長沼誠, 金井隆典, 江崎幹宏, 飯田智哉, 田中浩紀, 馬場重樹, 安藤朗, 清水俊明, 福田勝之, 鈴木英雄, 大北喜基, 松岡克善

  難治性炎症性腸管障害に関する調査研究 令和2年度 総括・分担研究報告書(Web)    2021

  J-GLOBAL

display all >>

Industrial Property Rights 【 display / non-display 】

Industrial Property Rights 【 display / non-display 】

• ステント、当該ステントを消化管に留置する方法

  仲瀬裕志, 樋口浩和

  Patent

• 病変評価情報生成装置

  仲瀬裕志, 松浦稔, 吉野琢哉, 樋口浩和, 池本洋祐

  Patent

• 画像処理装置及び内視鏡装置

  仲瀬裕志, 松浦稔, 吉野琢哉, 樋口浩和, 池本洋祐

  Patent

Research Projects 【 display / non-display 】

Research Projects 【 display / non-display 】

• クローン病肛門病変に対する間葉系幹細胞と細胞ファイバ技術を融合した細胞療法の開発

  基盤研究(C)

  Project Year :

  2022.04

  -

  2025.03

   

  永石 歓和, 仲瀬 裕志

• DOT1L阻害によるインターフェロン応答の機序解明とがん免疫療法への応用

  基盤研究(B)

  Project Year :

  2022.04

  -

  2025.03

   

  鈴木 拓, 仲瀬 裕志, 新沼 猛, 北嶋 洋志

• Functional analysis of small intestinal paneth cells in RalGAPa2 KO mice

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2021.04

  -

  2024.03

   

  林 優希, 仲瀬 裕志

  　View Summary

  本邦におけるクローン病 (Crohn’s disease: CD) 患者数は増加の一途をたどっているが，疾患の原因は未だ明らかとなっておらず，根治的な治療法は存在しない．申請者の研究室ではこれまでに，大腸上皮における低分子量GTP蛋白質Ralの活性化が，NLRP3 inflammasome を介した大腸炎及び炎症性大腸発癌 (colitis-associated cancer: CAC) に極めて重要であることを報告してきた．さらに，申請者が行った予備検討で，小腸炎症においてもRalの活性化が確認されていることから，RalがCDの小腸病変とも関連している可能性が高いと考えた．一方，CD発症の原因の一つとして腸管免疫機構の破綻が考えられており，中でも小腸粘膜免疫におけるPaneth 細胞の役割が注目されている．本研究では，Ral活性化のPaneth細胞機能における役割を解析することにより，CDの病態解明に取り組む．
  令和3年度と令和4年度は，SAMP1/YitFcマウスの繁殖，SAMP1/YitFc × RalGAPa2 KOマウス，SAMP1/YitFc × RalGAPa2 KO × NLRP3 KOマウスの作成とphenotypeの同定を遂行中である．

• 肝細胞癌の分子標的治療と概日時計の関連

  基盤研究(C)

  Project Year :

  2020.04

  -

  2023.03

   

  阿久津 典之, 佐々木 茂, 仲瀬 裕志

  　View Summary

  1. ヒト肝細胞癌における時計遺伝子発現の検討 肝細胞癌10症例の癌部および非癌部の組織よりRNAを作成しcDNAを合成。その後Comparative CT法を用いて相対的発現を解析した。Clock, Bmal1, Per1,Per2 Cry1の発現を癌部と非癌部で解析したところ、Per1およびPer2が癌部と非癌部で有意な発現の違いをあることが分かった。背景因子での違いがないかさらなる検 討を行っている。 2. 正常肝細胞および肝癌細胞株における時計遺伝子発現と炎症性サイトカインに対する反応 肝癌細胞株HepG2, Hep3B, HLE, HLF, HuH7, PLC/PRF/5のcDNAを用いて、Clock, Bmal1, Per1,Per2 Cry1の発現を解析し、細胞株間での発現に差があることがわ かり、Per1やPer2の発現が低い細胞株と、高い細胞株を用いて、種々の炎症性サイトカイン(IL-1β, IL-4, IL-13, TNF-α, IFN-γ, IL-10, TGF-β)の添加を行 い、RNAおよびタンパクを回収。時計遺伝子の変化を解析している。 3. 分子標的薬の正常肝細胞および肝癌細胞株における時計遺伝子の発現と炎症性サイトカインに対する反応 肝癌細胞株 (Hep3B, HLF, HuH7)にレンバチニブ1μMを投与 し、37°Cで48時間培養した後に、時計遺伝子Bmal1、Rev-erbα、Rev-erbβ、Per1、Per2、 Cry1の発現についてqPCR法、western blotting法を用い検討した。

• Development of human biopsy-derived intestinal organoids monolayers and application for pharmaceutical research

  Grant-in-Aid for Challenging Research (Pioneering)

  Project Year :

  2020.04

  -

  2022.03

   

  Mizuguchi Hiroyuki

  　View Summary

  The human small intestine is the key organ for absorption, metabolism, and excretion of orally administered drugs. To preclinically predict these reactions in drug discovery research, a cell model that can precisely recapitulate the in vivo human intestinal monolayer is desired. Here, we developed a monolayer platform using human biopsy-derived duodenal organoids for application to pharmacokinetic studies. The human duodenal organoid-derived monolayer was prepared by a simple method in 3 to 8 days. It consisted of polarized absorptive cells and had tight junctions. It showed much higher cytochrome P450 (CYP) 3A4 and carboxylesterase (CES) 2 activities than the existing models (Caco-2 cells). It also showed efflux activity of P-glycoprotein (P-gp) and inducibility of CYP3A4. This monolayer assay system can be a general platform for a wide range of applications including pharmaceutical research.

display all >>

Presentations 【 display / non-display 】

Presentations 【 display / non-display 】

• Acitvation of Innate immune response by osteopontine prevent onset of spontaneous colitis.

  Ueno S, Nakase H, Chiba T

  DDW 2009 

  Presentation date： 2009

• 難治性潰瘍性大腸炎に対するタクロリムス治療の手術回避効果とその背景因子に関する検討

  松浦 稔, 仲瀬裕志, 千葉 勉

  第19回日本消化器関連学会週間. 

  Presentation date： 2011

• 「炎症性腸疾患の免疫病態と治療法の新しい展開」 FK506のA20誘導による活性化マクロファージの制御について．

  吉野琢哉, 仲瀬裕志, 千葉 勉

  第46回日本消化器免疫学会総会. 

  Presentation date： 2009

• Measurement of serum diamine oxidase (DAO) activity can be a predictive factor of disease onset of human IBD.

  Honzawa Y, Nakase H, Matsumura K, Yamamoto S, Yoshino T, Takeda Y, Ueno S, Uza N, Chiba T

  DDW 2010. 

  Presentation date： 2010

• 「消化管粘膜と微生物との相互作用」 クローン病におけるMycobacteriumparatuberculosis IS900領域蛋白に対する血中抗体の意義.

  仲瀬裕志, 岡崎和一, 千葉 勉

  第87回日本消化器病学会総会 

  Presentation date： 2001

display all >>