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Autophagy and mitophagy in advanced hepatocellular carcinoma

Research Project

Project/Area Number 18K08647
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 55020:Digestive surgery-related
Research InstitutionJikei University School of Medicine (2020)
Kyushu University (2018-2019)

Principal Investigator

Ikegami Toru  東京慈恵会医科大学, 医学部, 教授 (80432938)

Co-Investigator(Kenkyū-buntansha) 間野 洋平  独立行政法人国立病院機構(九州がんセンター臨床研究センター), その他部局等, 肝胆膵外科医師 (10792244)
副島 雄二  信州大学, 学術研究院医学系, 教授 (30325526)
戸島 剛男  九州大学, 大学病院, 助教 (40608965)
本村 貴志  九州大学, 医学研究院, 共同研究員 (50719507)
吉住 朋晴  九州大学, 医学研究院, 准教授 (80363373)
原田 昇  九州大学, 大学病院, 講師 (80419580)
伊藤 心二  九州大学, 大学病院, 助教 (90382423)
後町 武志  東京慈恵会医科大学, 医学部, 助教 (40338893)
古川 賢英  東京慈恵会医科大学, 医学部, 助教 (80624973)
白井 祥睦  東京慈恵会医科大学, 医学部, 助教 (10785364)
恩田 真二  東京慈恵会医科大学, 医学部, 助教 (10459620)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords肝細胞癌 / オートファジー / 肝癌 / マイトファジー
Outline of Final Research Achievements

Immuno-histochemical staining for LC3 in hepatocellular carcinoma showed increased Beclin-1、LC3-II、Atg5 and decreased expression of p62. Knock out of autophagy resulted in decreased BrdU uptake and collection of p62. Immuno-histochemical staining for mitophcin in hepatocellular carcinoma showed positive staining in large and advanced ones. Recurrence free survival rate after hepatectomy for hepatocellular carcinoma was significantly worse in positive mitophcin cases. However, perkin was not a useful biomarker for survival rate.

Academic Significance and Societal Importance of the Research Achievements

従来の肝細胞癌研究に於いては、肝細胞癌のゲノム解析や免疫学的側面からその発育・浸潤・転移を明らかにするようなアプローチが殆どであり、細胞のエネルギー代謝・エネルギー産生やミトコンドリアサイクルからのアプローチは殆どされてこなかった。細胞内エネルギー状態の維持を行うオートファジー、障害ミトコンドリアの選択的排除により健常ミトコンドリアによるエネルギー産生を維持するマイトファジーの2つの生体機構が肝細胞癌の発育進展に於いてどのように作用し、またどのような分子機構により関与しているのか、従来と異なるアプローチから肝細胞癌の増殖進展のメカニズムを明らかにすることができた。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (13 results)

All 2020 2018

All Journal Article (8 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 8 results) Presentation (5 results)

  • [Journal Article] Extensive portal thrombectomy with secure shunt ligation should be more strongly emphasized in the real-world setting.2020

    • Author(s)
      Ikegami T, Yoshizumi T, Tomiyama T, Inokuchi S, Mori M.
    • Journal Title

      J Hepatol

      Volume: 72 Issue: 1 Pages: 199-201

    • DOI

      10.1016/j.jhep.2019.09.009

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Small-for-size graft, small-for-size syndrome and inflow modulation in living donor liver transplantation.2020

    • Author(s)
      Ikegami T, Onda S, Furukawa K, Haruki K, Shirai Y, Gocho T
    • Journal Title

      J Hepatobiliary Pancreat Sci.

      Volume: 27 Issue: 11 Pages: 799-809

    • DOI

      10.1002/jhbp.822

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Impact of Immune Response on Outcomes in Hepatocellular Carcinoma: Association with Vascular Formation2020

    • Author(s)
      Itoh Shinji、Yoshizumi Tomoharu、Yugawa Kyohei、Imai Daisuke、Yoshiya Shohei、Takeishi Kazuki、Toshima Takeo、Harada Noboru、Ikegami Toru、Soejima Yuji、Kohashi Kenichi、Oda Yoshinao、Mori Masaki
    • Journal Title

      Hepatology

      Volume: - Issue: 6 Pages: 1987-1999

    • DOI

      10.1002/hep.31206

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Charting the Path Forward for Risk Prediction in Liver Transplant for Hepatocellular Carcinoma: International Validation of HALTHCC Among 4,089 Patients.2020

    • Author(s)
      Firl DJ, Sasaki K, Ikegami T, Lerut J, et al.
    • Journal Title

      Hepatology

      Volume: 71 Issue: 2 Pages: 569-582

    • DOI

      10.1002/hep.30838

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Identification of an Upper Limit of Tumor Burden for Downstaging in Candidates with Hepatocellular Cancer Waiting for Liver Transplantation: A West-East Collaborative Effort.2020

    • Author(s)
      Lai Q, Vitale A, Halazun K, Iesari S, Viveiros A, Bhangui P, Mennini G, Wong T, Uemoto S, Lin CC, Mittler J, Ikegami T, Zhe Y, Zheng SS, Soejima Y, Hoppe-Lotichius M, Chen CL, Kaido T, Lo CM, Rossi M, Soin AS, Finkenstedt A, Emond JC, Cillo U, Lerut J.
    • Journal Title

      Cancers (Basel).

      Volume: 12 Issue: 2 Pages: 452-452

    • DOI

      10.3390/cancers12020452

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Lymphocyte-to-Monocyte Ratio Is a Predictor of Survival After Liver Transplantation for Hepatocellular Carcinoma.2018

    • Author(s)
      Mano Y, Yoshizumi T, Yugawa K, Ohira M, Motomura T, Toshima T, Itoh S, Harada N, Ikegami T, Soejima Y, Maehara Y.
    • Journal Title

      Liver Transpl.

      Volume: 24 Issue: 11 Pages: 1603-1611

    • DOI

      10.1002/lt.25204

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Impact of Splenic Volume and Splenectomy on Prognosis of Hepatocellular Carcinoma Within Milan Criteria After Curative Hepatectomy.2018

    • Author(s)
      Takeishi K, Kawanaka H, Itoh S, Harimoto N, Ikegami T, Yoshizumi T, Shirabe K, Maehara Y.
    • Journal Title

      World Journal of Surgery

      Volume: 42 Issue: 4 Pages: 1120-1128

    • DOI

      10.1007/s00268-017-4232-z

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Associations between antibody to hepatitis B core antigen positivity and outcomes in hepatocellular carcinoma patients undergoing hepatic resection.2018

    • Author(s)
      Itoh S, Yoshizumi T, Tomino T, Nagatsu A, Motomura T, Harada N, Harimoto N, Ikegami T, Soejima Y, Maehara Y.
    • Journal Title

      Hepatol Res.

      Volume: 48 Issue: 3

    • DOI

      10.1111/hepr.12939

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] 骨密度低下(オステオペニア)が生体肝移植後の予後に与える影響について2020

    • Author(s)
      戸島 剛男, 吉住 朋晴, 井口 詔1, 小斉 侑希子, 吉屋 匠平, 武石 一樹, 伊藤 心二, 原田 昇, 池上 徹, 森 正樹.
    • Organizer
      第75回日本消化器外科学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 注意を要する肝移植後C型肝炎治療2020

    • Author(s)
      池上 徹, 吉住 朋晴, 森 正樹
    • Organizer
      第106回日本消化器病学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 肝癌増殖におけるオートファジーアダプター蛋白質optineurin発現の意義2020

    • Author(s)
      井口 詔一, 吉住 朋晴, 戸島 剛男, 伊勢田 憲史, 冨山 貴央, 森永 哲成, 湯川 恭平, 小斉 侑希子, 吉屋 匠平, 武石 一樹, 伊藤 心二, 原田 昇, 池上 徹, 森 正樹
    • Organizer
      第120回日本外科学会定期学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 肝癌微小環境における癌関連線維芽細胞由来エクソソームの意義2020

    • Author(s)
      湯川 恭平, 吉住 朋晴, 間野 洋平, 伊勢田 憲史, 冨山 貴央, 森永 哲成, 小斎 侑希子, 井口 詔一, 吉屋 匠平, 武石 一樹, 戸島 剛男, 長尾 吉泰, 伊藤 心二, 原田 昇, 池上 徹, 森 正樹
    • Organizer
      第120回日本外科学会定期学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 大腸癌肝転移肝切除における外科感染症のリスク因子の検討と長期予後改善を目指した対策2020

    • Author(s)
      古川 賢英, 後町 武志, 谷合 智彦, 柳垣 充, 羽村 凌雅, 堀内 尭, 白井 祥睦, 安田 淳吾, 春木 孝一郎, 塩崎 弘憲, 恩田 真二, 池上 徹
    • Organizer
      第82回日本臨床外科学会総会
    • Related Report
      2020 Annual Research Report

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Published: 2018-04-23   Modified: 2022-01-27  

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