| Project/Area Number |
17K10860
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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 |
Neurosurgery
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| Research Institution | University of Yamanashi |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
齋藤 正夫 山梨大学, 大学院総合研究部, 教授 (90345041)
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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 |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | グリオーマ / 上皮間葉転換 / 浸潤能 / ZEB / 膠芽腫 / 浸潤 / ベバシズマブ / 薬剤抵抗性 / 脳神経疾患 |
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| Outline of Final Research Achievements |
We analyzed the pathogenesis of epithelia mesenchymal transition (EMT) in malignant glioms. We confirmed high expression of EMT transcription factors ZEB1 and ZEB2 with qPCR in 4 kind of human glioblastoma cell lines. In addition, we observed the synergistic inhibition of glioma migration by the siRNA inhibtion of ZEB1/2 expression in vitro. Furthermore, a correlation between expression of ZEB1/2 and histological malignancy was observed in immunohistochemical staining analysis. However, there was no sygnificant synergistic anti- tumor effect of ZEB1/2 inhibition on in the mouse subcutaneous implantation gloma model in vivo. We are going to focus on the relationship between bevacizumab-dependent invasion and these transcription factors.
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| Academic Significance and Societal Importance of the Research Achievements |
本検討では、グリオーマが上皮間葉転換（EMT)という形質転換により、組織における微小環境を巧みに変えて、浸潤や増殖し、これが薬剤抵抗性の根幹であるという仮説に基づき研究を始めた。グリオーマ株やヒトグリオーマ組織におけるEMT関連因子であるZEB1/2の発現が更新し、間葉系の形質を発現し浸潤能を更新している可能性が示唆されたが、Bevacizumab依存性浸潤能には、さらなる検討が必要である。
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