| Project/Area Number |
16K19656
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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 |
Pediatrics
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| Research Institution | University of Miyazaki |
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Principal Investigator |
Sawa Daisuke 宮崎大学, 医学部, 助教 (10632721)
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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 |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | ユーイング肉腫 / TAE226 / FAK / IGFIR / 細胞内シグナル / ユーイング肉腫ファミリー腫瘍 / focal adhesion kinase / IGF1R / ユーイング肉腫ファミリー 腫瘍 / IGF-1R / ESFT / Focal adhesion kinase |
|---|
| Outline of Final Research Achievements |
High focal adhesion kinase (FAK) transcript expression levels in EWS cell lines are known. TAE226 is a dual inhibitor of FAK and insulin-like growth factor-I receptor (IGF-IR), while PF-562,271 is a dual inhibitor of FAK and proline-rich tyrosine kinase 2. We compared the cytotoxicity of TAE226 and PF-562,271 toward three EWS cell lines. Furthermore, we investigated the efficacy of TAE226 as well as its mechanism of action against EWS. TAE226 strongly inhibited proliferation of three cell lines when compared with PF-562,271. TAE226 strongly inhibited proliferation of three cell lines when compared with PF-562,271. TAE226 treatment of EWS cell lines induced cell cycle arrest, apoptosis, AKT dephosphorylation, and inhibition of invasion. We demonstrated that TAE226 drastically inhibits the local growth of primary tumors and metastasis in EWS using mouse models. Furthermore, the combination of TAE226 and conventional chemotherapy proved to exert synergistic effects.
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| Academic Significance and Societal Importance of the Research Achievements |
再発および転移性ユーイング肉腫の予後は、非常に不良である。
従って、腫瘍特異性のターゲットを特定し治療を行うことは、予後を改善させるために重要である。今回、評価をおこなったTAE226は、単剤あるいは既存の化学療法薬との併用により再発/転移性ユーイング肉腫の予後を改善させる可能性がある。
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