Interplay between the molecular mechanism for hypoxia response and that for antioxidant capacity
| Project/Area Number |
17H04261
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Radiation science
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| Research Institution | Kyoto University |
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Principal Investigator |
Harada Hiroshi 京都大学, 生命科学研究科, 教授 (80362531)
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| Co-Investigator(Kenkyū-buntansha) |
子安 翔 京都大学, 生命科学研究科, 招へい研究員 (80781913)
小林 稔 京都大学, 放射線生物研究センター, 特定研究員 (40644894)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000)
Fiscal Year 2019: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2018: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2017: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
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| Keywords | がん / 低酸素応答 / 抗酸化能 / 放射線抵抗性 / 血中マーカー |
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| Outline of Final Research Achievements |
Cancer cells acquire radioresistance under hypoxic microenvironments. In order to elucidate biological mechanism behind it and establish a new therapeutic strategy, we focus on novel genes that may mediate “cellular adaptive response to hypoxia” and “cellular antioxidative activity”. We found that the expression of the novel gene was induced by a mechanism dependent of HIF-1β but not of either HIF-1α or HIF-2α. Moreover, we found that its gene product was secreted extracellularly. It was also confirmed that the gene product significantly reduced the number of DNA double-strand breaks after irradiation and induces radioresistance of cancer cells in a autocrine fashion. We further found the possibility of establishing a system for monitoring the amount of tumor hypoxia using the blood concentration of the gene product.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究で研究代表者らは、「細胞の低酸素応答機構」と「細胞の抗酸化能亢進機構」を介在する機能を持つ可能性を見出していた新規遺伝子に着目して、in vitroとin vivoの研究を展開した。そして、当該遺伝子産物の機能を抑制することによって、放射線治療効果を増感できることが確認された。また、当該遺伝子産物の血中濃度を指標に、腫瘍内低酸素の量をモニターできる可能性が示された。本研究により、放射線治療効果の増強と、腫瘍低酸素のモニターを可能とする手法を確立する礎が築かれた。
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Report
(4 results)
Research Products
(49 results)
