Pathological study of cancer-related sarcopenia focusing on the Gut-muscle axis and development of new treatments
Project/Area Number |
20K07787
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 52010:General internal medicine-related
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Research Institution | Kyoto 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)
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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)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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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)
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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。
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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.
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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。
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Report
(4 results)
Research Products
(14 results)
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[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.
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Journal Title
Oncology Reports
Volume: 44
Issue: 1
Pages: 371-381
DOI
Related Report
Peer Reviewed
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[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.
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Journal Title
Oncology Letters
Volume: 20
Pages: 14-14
DOI
Related Report
Peer Reviewed / Open Access
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[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
Int'l Joint Research
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[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
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