Pathological analysis and examination of cytoskeleton-targeted therapy for overcoming cardiotoxicity caused by radiation
| Project/Area Number |
20K16801
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 52040:Radiological sciences-related
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| Research Institution | Keio University |
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Principal Investigator |
Naoyoshi Koike 慶應義塾大学, 医学部(信濃町), 特任講師 (60464913)
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| Project Period (FY) |
2020-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2020: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 放射線心毒性 / 細胞骨格 / 放射線治療 / 心毒性 |
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| Outline of Research at the Start |
放射線治療で肺がん、食道がんを含む胸部悪性腫瘍は根治可能な疾患となりつつある。一方で長期生存が達成されることで、新たに顕在化した問題として胸部放射線治療による晩発性の心毒性がある。放射線誘発性の心毒性発症のメカニズムは不明な点が多く、予防法や根本的治療法は確立されていない。そこで、本研究では、照射による心毒性のメカニズムの解明と心毒性の軽減を目指して、筋線維芽細胞を標的とした治療の確立をマウスモデルで試みる。
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| Outline of Final Research Achievements |
Cardiotoxicity after irradiation for thoracic malignancies has become a major problem. To overcome radiation-induced cardiotoxicity, we investigated the establishment of a mouse model of radiation-induced cardiotoxicity and the morphological and pathological changes in the heart of the mouse model.
The heart of the mouse was irradiated, the heart was removed, and the effect of radiation on the heart was pathologically evaluated. In the mouse heart after irradiation, the epicardium and aortic valve around the right ventricle were thickened and fibrotic, and angiogenesis and cell infiltration were observed in the epicardium. Administration of fasdil, which has an antifibrotic effect, improved the thickening of the mouse aortic valve. CT showed improvement in the enlarged findings of the right atrium.
The thickening and fibrosis of the aortic valve caused by irradiation of the heart were improved by administration of Fasdil.
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| Academic Significance and Societal Importance of the Research Achievements |
乳がん、肺がん、食道がんなどの胸部領域において放射線治療による心毒性が明らかになってきている。放射線治療による心毒性の軽減の原因と治療法の探索が求められている。
本研究で照射による心毒性の原因として心外膜の線維化及び大動脈弁の肥厚が示唆され、タンパクリン酸化阻害薬であるファスジル投与により心毒性が軽減される可能性を見出した。
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Report
(3 results)
Research Products
(3 results)
