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Comprehensive elucidation of intrahepatic biliary carcinogenesis induced by IDH mutations

Research Project

Project/Area Number 19K17391
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 53010:Gastroenterology-related
Research InstitutionThe Institute for Adult Diseases Asahi Life Foundation

Principal Investigator

Fujiwara Hiroaki  公益財団法人朝日生命成人病研究所, その他部局等, 教授(移行) (00814500)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords胆管癌 / 代謝 / エピゲノム / 肝内胆管癌 / IDH変異 / IDH
Outline of Research at the Start

依然予後不良な肝内胆管癌(ICC)において、その病態解明及び治療標的の同定は急務である。本研究では約20%の症例に存在するIDH変異陽性ICCの発癌過程を明らかにすることで、新たな分子標的の探索に繋げることを目的とする。

Outline of Final Research Achievements

By combining mutations in chromatin remodeling-related genes and abnormalities in the phosphatidylinositol 3-kinase pathway with IDH1 mutation, we succeeded in creating a multi-step carcinogenesis model from normal intrahepatic biliary epithelial cells to cholangiocarcinoma. As the next step, focusing on the histological differences between the IDH-wildtype models and IDH-mutant ones, we will plan to elucidate the molecular mechanism by several methods including comprehensive gene expression analysis.

Academic Significance and Societal Importance of the Research Achievements

近年、がん遺伝子パネル検査が保険適応なるなど、がん治療の個別化に向けた潮流は顕著になりつつある。基本的な戦略は各患者ごとに異なる癌固有の遺伝子変異に即した治療を行う、という方向性になるが、残念ながら現状ではそのような治療を享受することの出来る患者は1割程度と少ない。IDH変異は肝内胆管癌の約20%に存在する変異であるが、変異陽性癌に対する有効な治療法は目下確立されていない。本研究の成果により、その発癌に至るメカニズムを解明することが出来れば、IDH変異特異的に有効な治療法の開発へと繋げていくことが期待される。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (11 results)

All 2022 2021 2020 2019

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (8 results) (of which Int'l Joint Research: 1 results) Book (1 results)

  • [Journal Article] 5-Aminolevulinic acid-mediated photodynamic activity in patient-derived cholangiocarcinoma organoids2020

    • Author(s)
      Fujiwara Hiroaki、Takahara Naminatsu、Tateishi Keisuke、Tanaka Mariko、Kanai Sachiko、Kato Hiroyuki、Nakatsuka Takuma、Yamamoto Keisuke、Kogure Hirofumi、Arita Junichi、Nakai Yousuke、Kasuga Masato、Ushiku Tetsuo、Hasegawa Kiyoshi、Koike Kazuhiko
    • Journal Title

      Surgical Oncology

      Volume: 35 Pages: 484-490

    • DOI

      10.1016/j.suronc.2020.10.011

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Mutant IDH1 confers resistance to energy stress in normal biliary cells through PFKP-induced aerobic glycolysis and AMPK activation2019

    • Author(s)
      Fujiwara H、Tateishi K、Misumi K、Hayashi A、Igarashi K、Kato H、Nakatsuka T、Suzuki N、Yamamoto K、Kudo Y、Hayakawa Y、Nakagawa 、Tanaka Y、Ijichi H、Kogure H、Nakai Y、Isayama H、Hasegawa K、Fukayama M、Soga T、Koike K
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 18859-18859

    • DOI

      10.1038/s41598-019-55211-w

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 患者組織検体を用いた原発性硬化性胆管炎における特異的分子病態の探索2022

    • Author(s)
      金井祥子、藤原弘明、藤城光弘
    • Organizer
      第108回 日本消化器病学会総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Mutant IDH1 creates the tumorigenic precondition in biliary cells through PFKP-induced aerobic glycolysis and AMPK activation2022

    • Author(s)
      Hiroaki Fujiwara, Keisuke Tateishi, Hiroyuki Kato, Takuma Nakatsuka, Keisuke Yamamoto, Yotaro Kudo, Kiyoshi Hasegawa, Tomoyoshi Soga, Kazuhiko Koike and Mitsuhiro Fujishiro
    • Organizer
      Digestive Disease Week 2022
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ヒト臨床検体由来オルガノイドを利用した、5-アミノレブリン酸による胆管癌の光線力学的診断の可能性についての検討2021

    • Author(s)
      藤原弘明、高原楠昊、中井陽介、立石敬介、春日雅人、小池和彦
    • Organizer
      第31回日本光線力学学会学術講演会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 患者由来オルガノイドを用いた胆道癌診断における5-アミノレブリン酸の有用性の検討2021

    • Author(s)
      藤原弘明、高原楠昊、小池和彦
    • Organizer
      第107回 日本消化器病学会総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 患者由来オルガノイドを用いた胆管癌診断における5-アミノレブリン酸の有用性の検討2021

    • Author(s)
      藤原弘明、高原楠昊、小池和彦
    • Organizer
      第107回日本消化器病学会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] 胆道癌ゲノム医療に向けたIDH変異陽性肝内胆管癌の標的分子に関する基礎的検討2019

    • Author(s)
      藤原弘明、立石敬介、小池和彦
    • Organizer
      第55回日本胆道学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 肝内胆管上皮におけるIDH1変異の機能的役割2019

    • Author(s)
      藤原弘明、三角健人、林玲匡 、加藤裕之、中塚拓馬、田中康雄 、伊地知秀明、深山正久、曽我朋義 、小池和彦
    • Organizer
      第56回日本臨床分子医学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] Increased susceptibility to BET inhibition in IDH1-mutant intrahepatic cholangiocarcinoma.2019

    • Author(s)
      Hiroaki Fujiwara, Keisuke Tateishi, Hiroyuki Kato, Takuma Nakatsuka, Yasuo Tanaka, Hideaki Ijichi, and Kazuhiko Koike
    • Organizer
      Digestive Disease Week (DDW) 2019
    • Related Report
      2019 Research-status Report
  • [Book] Medical Practice2020

    • Author(s)
      藤原弘明、高原楠昊
    • Total Pages
      3
    • Publisher
      文光堂
    • Related Report
      2020 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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