| Project/Area Number |
18K15602
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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 |
Koike Naoyoshi 慶應義塾大学, 医学部(信濃町), 助教 (60464913)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 低酸素 / 放射線治療 / 膠芽腫 / 2－ニトロイミダゾール化合物 / theranostics / がん幹細胞 / 2-ニトロイミダゾール / 幹細胞 / 放射線抵抗性 |
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| Outline of Final Research Achievements |
The radioresistance of glioblastoma is caused by the hypoxic region in the tumor. The nitroimidazole compounds that accumulates specifically in the hypoxic region were analyzed for overcoming radioresistance. Among nitroimidazole compounds, doranidazole had a radiosensitizing effect in the hypoxic region of glioblastoma and a cell-killing effect by itself. The mechanism of cell death by doranidazole was mitochorial stress. In the allogeneic orthotopic mouse brain tumor model, the combined use of doranidazole and irradiation contributed to prolongation of mouse survival.
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| Academic Significance and Societal Importance of the Research Achievements |
膠芽腫は放射線治療抵抗性であることが多く、膠芽腫を制御するために放射線増感剤が求められている。本研究で膠芽腫に対する有望な放射線増感剤としてドラニダゾールを見出した。低酸素マーカーとして診療で使用されている18F-FMISOと同じ2-ニトロイミダゾール化合物であり、薬剤集積と効果予測とがたてやすいという利点がある。臨床試験に進む前段階の研究を行うことができた。
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