| Project/Area Number |
18K09096
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 56020:Orthopedics-related
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
Katsushi Kikuchi 東京医科歯科大学, 大学院医歯学総合研究科, 非常勤講師 (00602062)
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| Co-Investigator(Kenkyū-buntansha) |
佐藤 信吾 東京医科歯科大学, 医学部附属病院, 講師 (40462220)
麻生 義則 東京医科歯科大学, 大学院医歯学総合研究科, ジョイントリサーチ講座教授 (50345279)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 肉腫 / PAI-1 / がん幹細胞 |
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| Outline of Final Research Achievements |
When the expression of PAI-1 was analyzed using qPCR method and immunostaining method using the sarcoma sample removed from the mouse sarcoma model, the expression of PAI-1 in the sarcoma was confirmed. Pai-1 inhibitors were acted on human sarcoma cell cells and human mesenchymal stem cells to analyze their effects on growth activity. As a result, it was clarified that PAI-1 inhibitors have a significant effect on cell proliferation in the sarcoma cell system in a dose-dependent manner, and that the activity is not observed in human mesenchymal stem cells. Currently, RNA-seq analysis is employed to analyze the molecular mechanism of PAI-1 inhibitors for sarcoma cells.
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| Academic Significance and Societal Importance of the Research Achievements |
抗がん剤が大半の骨軟部肉腫に作用し難いことは、肉腫治療における大きな課題である。また、高悪性肉腫の場合は、肉眼的には完全に肉腫を切除できた場合でも、しばしば再発や転移が問題となり、このような症例は抗がん剤治療のみではコントロールができず、予後不良となる。このため、抗がん剤に代わるもしくは抗がん剤と併用する新たな肉腫治療薬が希求されている。PAI-1阻害薬はがん幹細胞ニッチからの肉腫幹細胞の離脱を促進し、抗がん剤の感受性を増強させる画期的な新規肉腫治療薬となる可能性があり、化学療法と併用することで、再発および転移の抑制を十分期待できる。
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