| Project/Area Number |
16H05471
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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 |
Obstetrics and gynecology
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| Research Institution | Shinshu University |
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Principal Investigator |
Shiozawa Tanri 信州大学, 学術研究院医学系, 教授 (20235493)
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| Co-Investigator(Kenkyū-buntansha) |
鹿島 大靖 信州大学, 学術研究院医学系(医学部附属病院), 講師 (70464089)
浅香 亮一 信州大学, 学術研究院医学系(医学部附属病院), 助教 (00623688)
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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 |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2018: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2017: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2016: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
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| Keywords | 子宮体癌 / 細胞周期調節因子 / 低分子化合物 / サイクリンA / 化合物X / 子宮内膜癌 / 抗がん剤 / 婦人科腫瘍学 / 分子標的薬 / 創薬 / 抗腫瘍薬 / 抗癌剤感受性 |
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| Outline of Final Research Achievements |
Because the number of endometrial carcinoma (EMCa) patients is markedly increasing in recent years, development of novel drugs for EMCa is mandatory. We previously revealed that the expression of cyclin A, an important cell-cycle regulator, was involved in the acquisition of malignant potentials of EMCa. Therefore we aimed to develop new drugs which suppress cyclin A activity.
The screening of low molecular weight compound library using luciferase assay containing cyclin A promoter identified “compound X”, which had strong anti-cyclin A transcriptional activity. The compound X also showed strong anti-proliferative activity for EMCa cells in vitro and in vivo. We then altered the partial structure of compound X, and newly synthesized compound X1. The compound X1 had anti-proliferative activity 10 times stronger than that of compound X. There results indicated the newly synthesized compound X1 is a promising agent.
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| Academic Significance and Societal Importance of the Research Achievements |
子宮体癌の増加にともなって、難治性の進行癌が増加している。現在こういった症例に対しては、シスプラチンやタキソールなどによる治療が行われているが、効果は限定的であった。今回我々が開発した化合物X1は、従来までの抗癌剤とはまったく異なり、子宮体癌の生物学特性の解析から開発されたものであり、その将来性は非常に有望であると考えられる。
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