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Pathological study of cancer-related sarcopenia focusing on the Gut-muscle axis and development of new treatments

Research Project

Project/Area Number 20K07787
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52010:General internal medicine-related
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

ISHIKAWA TAKESHI  京都府立医科大学, 医学(系)研究科(研究院), 講師 (90372846)

Co-Investigator(Kenkyū-buntansha) 内藤 裕二  京都府立医科大学, 医学(系)研究科(研究院), 教授 (00305575)
岡山 哲也  京都府立医科大学, 医学(系)研究科(研究院), 助教 (30636535)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsがんサルコペニア / 腸内細菌 / 腸内細菌叢 / 水溶性食物繊維 / Gut-muscle axis / サルコペニア / がん
Outline of Research at the Start

がんサルコペニアの病態形成には、免疫・慢性炎症・代謝異常など様々な要因が関与しているが、がん患者において腸内細菌叢のサルコペニア病態形成への影響については不明である。本研究では、マウスがんサルコペニアモデルを用いて、がんサルコペニアにおける”腸筋相関”の存在を明らかにする。その上で、腸内細菌叢を標的とした新たな治療法開発のための動物実験を行い、その研究成果を臨床に還元することを目指す。

Outline of Final Research Achievements

The involvement of the intestinal microbiota in the pathogenesis of cancer sarcopenia was investigated in a mouse model. Mice were divided into four groups according to the presence or absence of tumor transplantation and the presence or absence of soluble dietary fiber in the diet. Body weight and skeletal muscle weight were significantly decreased by tumor transplantation, but the intake of soluble dietary fiber significantly suppressed these reductions. Analysis of intestinal microbiota, metabolites, circulating bioactive substances, and gene expression in muscle revealed that soluble dietary fiber intake improves the intestinal environment in tumor-bearing mice, suppresses the systemic inflammatory response through the correction of intestinal barrier function and increased production of short chain fatty acids, resulting in suppression of protein catabolism in skeletal muscle. These results indicate that the gut-muscle axis is a potential therapeutic target for cancer sarcopenia.

Academic Significance and Societal Importance of the Research Achievements

がんサルコペニアはがん患者の生活の質(QOL)を低下させ、様々な治療に抵抗性を示し、予後にも悪影響を与えることが報告されているが、未だ有効な治療法はない。本研究は、がんサルコペニアの病態形成においてgut-muscle axisが存在することを証明し,担がんに伴う腸内細菌叢の変化が腸内環境・腸内代謝産物を変化させ、全身性の炎症を惹起することで骨格筋異化を亢進しているというメカニズムを明らかにした。さらに水溶性食物繊維による腸内環境の是正ががんサルコペニアの進展を抑制することを示し、gut-muscle axisが新たながんサルコペニア治療の標的となる可能性を示した点で臨床的意義は大きい。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (14 results)

All 2022 2021 2020 2019

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Open Access: 5 results) Presentation (5 results) (of which Int'l Joint Research: 1 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Water‐soluble dietary fiber alleviates cancer‐induced muscle wasting through changes in gut microenvironment in mice2022

    • Author(s)
      Sakakida Tomoki、Ishikawa Takeshi、Doi Toshifumi、Morita Ryuichi、Endo Yuki、Matsumura Shinya、Ota Takayuki、Yoshida Juichiro、Hirai Yasuko、Mizushima Katsura、Higashimura Yasuki、Inoue Ken、Okayama Tetsuya、Uchiyama Kazuhiko、Takagi Tomohisa、Abe Aya、Inoue Ryo、Itoh Yoshito、Naito Yuji
    • Journal Title

      Cancer Science

      Volume: 113 Issue: 5 Pages: 1789-1800

    • DOI

      10.1111/cas.15306

    • Related Report
      2022 Annual Research Report 2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of concomitant use of G-CSF and myelosuppressive chemotherapy on bone marrow and peripheral granulocytes in a mouse model2022

    • Author(s)
      Endo Yuki、Ishikawa Takeshi、Oka Kaname、Sakakida Tomoki、Matsumura Shinya、Mizushima Katsura、Doi Toshifumi、Okayama Tetsuya、Katada Kazuhiro、Kamada Kazuhiro、Uchiyama Kazuhiko、Takagi Tomohisa、Fujiwara Hitoshi、Konishi Hideyuki、Naito Yuji、Itoh Yoshito
    • Journal Title

      Medical Oncology

      Volume: 39 Issue: 8 Pages: 110-110

    • DOI

      10.1007/s12032-022-01725-9

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Proton Pump Inhibitors Enhance the Antitumor Effect of Chemotherapy for Esophageal Squamous Cell Carcinoma2022

    • Author(s)
      Matsumura Shinya、Ishikawa Takeshi、Yoshida Juichiro、Morita Ryuichi、Sakakida Tomoki、Endo Yuki、Doi Toshifumi、Hirose Ryohei、Inoue Ken、Dohi Osamu、Yoshida Naohisa、Uchiyama Kazuhiko、Takagi Tomohisa、Konishi Hideyuki、Yasui Kohichiroh、Naito Yuji、Itoh Yoshito
    • Journal Title

      Cancers

      Volume: 14 Issue: 10 Pages: 2395-2395

    • DOI

      10.3390/cancers14102395

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Treatment with broad-spectrum antibiotics upregulates Sglt1 and induces small intestinal villous hyperplasia in mice2022

    • Author(s)
      Ota Takayuki、Ishikawa Takeshi、Sakakida Tomoki、Endo Yuki、Matsumura Shinya、Yoshida Juichirou、Hirai Yasuko、Mizushima Katsura、Oka Kaname、Doi Toshifumi、Okayama Tetsuya、Inoue Ken、Kamada Kazuhiro、Uchiyama Kazuhiko、Takagi Tomohisa、Konishi Hideyuki、Naito Yuji、Itoh Yoshito
    • Journal Title

      Journal of Clinical Biochemistry and Nutrition

      Volume: 70 Issue: 1 Pages: 21-27

    • DOI

      10.3164/jcbn.21-42

    • NAID

      130008139090

    • ISSN
      0912-0009, 1880-5086
    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Metformin inhibits TGF-β1-induced epithelial-mesenchymal transition and liver metastasis of pancreatic cancer cells2020

    • Author(s)
      Yoshida J, Ishikawa T, Endo Y, Matsumura S, Ota T, Mizushima K, Hirai Y, Oka K, Okayama T, Sakamoto N, Inoue K, Kamada K, Uchiyama K, Takagi T, Naito Y, Itoh Y.
    • Journal Title

      Oncology Reports

      Volume: 44 Issue: 1 Pages: 371-381

    • DOI

      10.3892/or.2020.7595

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Safety and tolerability of PD-1/PD-L1 inhibitors in elderly and frail patients with advanced malignancies.2020

    • Author(s)
      Sakakida T, Ishikawa T, Uchino J, Tabuchi Y, Komori S, Asai J, Arai A, Tsunezuka H, Kosuga T, Konishi H, Hongo F, Inoue M, Hirano S, Ukimura O, Taguchi T, Takayama K, Itoh Y.
    • Journal Title

      Oncology Letters

      Volume: 20 Pages: 14-14

    • DOI

      10.3892/ol.2020.11875

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Safety and efficacy of PD-1/PD-L1 blockade in patients with preexisting antinuclear antibodies2019

    • Author(s)
      Sakakida T.、Ishikawa T.、Chihara Y.、Harita S.、Uchino J.、Tabuchi Y.、Komori S.、Asai J.、Narukawa T.、Arai A.、Tsunezuka H.、Kosuga T.、Konishi H.、Moriguchi M.、Yasuda H.、Hongo F.、Inoue M.、Hirano S.、Ukimura O.、Itoh Y.、Taguchi T.、Takayama K.
    • Journal Title

      Clinical and Translational Oncology

      Volume: 22 Issue: 6 Pages: 919-927

    • DOI

      10.1007/s12094-019-02214-8

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Presentation] Modulation of the gut microenvironment by water-soluble dietary fiber alleviates cancer-induced muscle wasting in mice2022

    • Author(s)
      Tomoki Sakakida, Takeshi Ishikawa, Toshifumi Doi, Ryuichi Morita, Yuki Endo, Shinya Matsumura, Takayuki Ota, Juichiro Yoshida, Katsura Mizushima, Yasuko Hirai, Yasuki Higashimura, Ken Inoue, Tetsuya Okayama, Kazuhiko Uchiyama, Tomohisa Takagi, Aya Abe , Ryo Inoue, Yoshito Itoh and Yuji Naito
    • Organizer
      AACR ANNUAL MEETING 2022
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Water-soluble dietary fiber alleviates cancer-induced muscle wasting through changes in gut microenvironment in mice2022

    • Author(s)
      榊田智喜、石川 剛、内藤裕二
    • Organizer
      第108回日本消化器病総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Therapeutic strategies targeting the gut microbiota in cancer-related sarcopenia2022

    • Author(s)
      榊田智喜、石川 剛、内藤裕二
    • Organizer
      第60回日本癌治療学会総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Potential of targeting the gut-muscle axis for the treatment of cancer related sarcopenia2021

    • Author(s)
      Tomoki Sakakida, Takeshi Ishikawa, Ryuichi Morita, Katsura Mizushima, Yasuko Hirai, Tetsuya Okayama, Toshifumi Doi, Kazuhiro Katada, Kazuhiko Uchiyama, Tomohisa Takagi, Yuji Naito and Yoshito Itoh
    • Organizer
      第80回日本癌学会学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] Gut-muscle axisを標的としたがんサルコペニア治療の可能性2021

    • Author(s)
      榊田智喜,石川剛,伊藤義人
    • Organizer
      第107回日本消化器病学会総会
    • Related Report
      2021 Research-status Report
  • [Patent(Industrial Property Rights)] ユビキチンリガーゼ阻害組成物、及びこれを含有しガンによって誘導されたカヘキシアを改善するための予防及び/又は治療用組成物2021

    • Inventor(s)
      石川 剛、小関 誠、安部 綾、内藤 裕二、髙木 智久、
    • Industrial Property Rights Holder
      京都府公立大学法人, 太陽化学株式会社
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2021-006790
    • Filing Date
      2021
    • Related Report
      2021 Research-status Report
  • [Patent(Industrial Property Rights)] ユビキチンリガーゼ阻害組成物、及びこれを含有しガンによって誘導されたカヘキシアを改善するための予防及び/又は治療用組成物2021

    • Inventor(s)
      小関誠、安部綾、内藤裕二、高木智久、石川剛
    • Industrial Property Rights Holder
      小関誠、安部綾、内藤裕二、高木智久、石川剛
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2021-006790
    • Filing Date
      2021
    • Acquisition Date
      2021
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2024-01-30  

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