| Project/Area Number |
17K16867
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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 |
Obstetrics and gynecology
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| Research Institution | Keio University |
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Principal Investigator |
IIJIMA Tomoko 慶應義塾大学, 医学部(信濃町), 助教 (30645271)
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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 |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 卵巣明細胞癌 / HOX遺伝子 / 卵巣がん / HOXD10 / HOXD9 / NFk-b / HOXA10 / NF-kB / 卵巣明細胞腺癌 |
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| Outline of Final Research Achievements |
In this study, we first examined the involvement of HOXA10 in proliferation, but its effect was limited. Next, a similar study was conducted targeting HOXD9. As a result, in the HOXD9 knoked-down ovarian clear cell adenocarcinoma cell line, cell proliferation was remarkably supressued.This result suggested that HOXD9 is deeply involved in the malignant phenotype. The existing drugs were screened for the purpose of developing a highly safe inhibitor capable of inhibiting the growth of clear cell adenocarcinoma of the ovary. As a result of screening the existing drug library, multiple drugs were identified. When examined with curcumin, which is one of the drugs obtained by this screening, the tumor growth was significantly suppressed by the combined use with the PD-L1 antibody.
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| Academic Significance and Societal Importance of the Research Achievements |
卵巣明細胞腺癌は治療抵抗性で、再発・進行症例では有効な治療法がない。近年、転写因子であるHOX遺伝子群が多くの癌の悪性化に関与するとされている。今回の検討で当初目的としたHOXA10の明細胞癌の悪性化への関与は示すことができなかったが、HOXD9については増殖能に関与することが示された。新たな治療法の開発のため、既存薬スクリーニングで複数の既存薬を同定することができた。今後、ドラッグリポジショニングの候補薬となる可能性がある。その中でクルクミンが抗PDL-1抗体との併用で抗腫瘍効果が高まると示したことは新たな免疫チェックポイント阻害薬の併用療法につながる可能性がある。
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