| Project/Area Number |
17K10122
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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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| Research Field |
Pediatrics
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
Iehara Tomoko 京都府立医科大学, 医学(系)研究科(研究院), 准教授 (20285266)
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| Co-Investigator(Kenkyū-buntansha) |
柳生 茂希 京都府立医科大学, 医学(系)研究科(研究院), 助教 (10572547)
細井 創 京都府立医科大学, 医学(系)研究科(研究院), 教授 (20238744)
菊地 顕 京都府立医科大学, 医学(系)研究科(研究院), 特任助教 (40453104)
宮地 充 京都府立医科大学, 医学(系)研究科(研究院), 助教 (40584983)
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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 |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 小児がん / HDAC阻害剤 / アポトーシス / 神経芽腫 / 横紋筋肉腫 / 小児腫瘍 |
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| Outline of Final Research Achievements |
Introduction: We investigated whether the novel HDAC inhibitor YM753 has an antitumor effect on rhabdomyosarcoma and neuroblastoma in cell lines and in animal models. Methods: The rhabdomyosarcoma and neuroblastoma cell lines were used. The antitumor effect and mechanism were examined. A xenograft mouse model was prepared to examine the antitumor effects. Results: This drug induced cell death in rhabdomyosarcoma and neuroblastoma cell lines. Induction of apoptosis was confirmed, showing G2/M phase arrest. The tumor cells showed G2/M phase arrest, confirming apoptosis induction. In addition, p21 expression induction, histone acetylation, and Cleaved caspase-3 induction were confirmed. In a mouse model, it suppressed tumor growth. In neuroblastoma it also induced differentiation. Discussion: From these results of culture experiments and animal experiments, it was effective as a novel therapeutic agent for rhabdomyosarcoma and neuroblastoma.
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| Academic Significance and Societal Importance of the Research Achievements |
新規 HDAC 阻害剤 YM753 が、横紋筋肉腫、神経芽腫に対して、培養細胞および動物実験モデルで抗腫瘍効果を検討した。細胞株およびマウスモデルにおいては、腫瘍増殖を抑制した。神経芽腫では、分化も誘導した。これらの細胞培養実験、動物実験の結果から、横紋筋肉腫、神経芽腫の新規治療薬として有効であると考えられた。現在phase 1試験が米国で実施されていることから、小児がん領域での本薬剤の臨床応用が期待される。
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