Elucidation of the pathophysiology of cancer cachexia-induced cardiac dysfunction and development of novel therapeutic approaches using exercise and nutrition interventions.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K11490
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 59020:Sports sciences-related
• Research Institution: University of Occupational and Environmental Health, Japan
• Principal Investigator: Ueno Susumu 産業医科大学, 産業生態科学研究所, 教授 (00279324)
• Co-Investigator(Kenkyū-buntansha): 野中 美希 東京慈恵会医科大学, 医学部, 特任講師 (60758077)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: がん悪液質 / モデルマウス / 心機能障害 / ユビキチンープロテアソーム系 / 自発運動

Outline of Final Research Achievements

The purpose of this study was to elucidate the pathogenesis of cardiac dysfunction in a mouse model of cancer cachexia in which 85As2 human gastric cancer cell line was transplanted, and to examine the possibility of improving such cardiac dysfunction through nutritional support. We found that the ubiquitin-proteasome system is upregulated in the myocardium of cancer cachexia model mice, and that this upregulation is suppressed by the application of spontaneous exercise. In addition, surgical resection of the tumor markedly improved cancer cachexia symptoms, suggesting that 85As2-derived factors probably play an important role in the development of cancer cachexia and cardiac dysfunction. The effect of flavonoids on the enhancement of the ubiquitin-proteasome system is currently under investigation.

Free Research Field

神経薬理学

Academic Significance and Societal Importance of the Research Achievements

本研究により、がん悪液質に伴う心機能障害の発症機序にはユビキチン－プロテアソーム系の亢進が関与していること、自発運動負荷はこの亢進を抑制することが判明したことから、この心機能障害に対して運動療法が導入できることが期待される。さらに、心筋のユビキチン－プロテアソーム系に対して選択的にその亢進を阻害する化合物は、補助療法として運動療法と併用できるものにつながる可能性が考えられることから、フラボノイドを中心にこのような作用を示す栄養素を探索する予定である。