| Project/Area Number |
16K18468
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Tumor therapeutics
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| Research Institution | Kanagawa Cancer Center Research Institute |
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Principal Investigator |
Muroi Atsushi 地方独立行政法人神奈川県立病院機構神奈川県立がんセンター(臨床研究所), その他部局等, 技師・研究員 (60609402)
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| Research Collaborator |
Yamada Roppei
Miyagi Yohei
Sawasaki Tatsuya
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 卵巣がん / 分子標的治療薬 / 細胞死 / 分子標的薬 / 癌 |
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| Outline of Final Research Achievements |
Since ovarian cancer is difficult to be detected earlily, therapeutic outcomes are poor. Therefore, development of novel therapeutic treatments against it is necessary. PACMAs belong to a grope of compounds selected from chemical libraries based on their characteristics including toxicity and hydrophobicity. So far, we have shown that a novel PACMA compound, PACMA-X, specifically kills various kinds of tumor cells including ovarian ones. In this study, we aimed to clarify mechanisms underlying the cell death. We found that a novel PACMA-X-binding protein, protein1, was involved in ROS production in mitochondria of PACMA-X-treated ovarian cells, which was essential for PACMA-X-induced cell death. Furthermore, we showed that the cell death had characteristics different from those of apoptosis or necroptosis.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、卵巣がん腹膜播種に対する新規治療薬候補化合物について作用メカニズムの詳細な解明を試みた。その結果、ターゲットタンパク質および細胞死におけるその機能について明らかにした。更に、本化合物によって引き起こされる細胞死が一般的ながん治療薬とは異なる形式のものである可能性を示唆する結果を得た。これらの結果は、本化合物を新たな卵巣がん治療薬として臨床応用する上で重要であるだけでなく、既存のがん治療薬に対し耐性を示す他のがん種への応用の可能性を示すものである。
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