| Project/Area Number |
17K10863
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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 | Kobe University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
甲村 英二 神戸大学, 医学研究科, 教授 (30225388)
田中 一寛 神戸大学, 医学研究科, 助教 (70467661)
水川 克 神戸大学, 医学部附属病院, 非常勤講師 (80403260)
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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: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | glioblastoma / dissemination / STC1 / microRNA / glioma / metastasis / グリオーマ / マイクロRNA / Glioma |
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| Outline of Final Research Achievements |
Using 76 GBM tissues, we examined the expression levels of 23 GBM-related miRs and compared the miRs' expression levels between GBMs with metastatic dissemination and GBMs without metastatic dissemination. By the bioinformatics analysis, we identified stanniocalcin-1 (STC1) as the most probable target gene. mRNA expression of STC1 was downregulated by miRs. Also, mimics of these miRs and knockdown of STC1 by siRNA suppressed invasion in GBM cells. GBM with metastatic dissemination had significantly higher levels of STC1 than GBM without metastatic dissemination. Finally, Kaplan-Meier analysis demonstrated that GBMs with high STC1 level had significantly shorter survival than GBMs with low STC1 level.
STC1 may be a novel metastatic dissemination promoting factor regulated by several miRs in GBM. Because STC1 is a secreted glycoprotein and functions via the autocrine/paracrine signals, inhibiting STC1 signal may become a novel therapeutic strategy for GBM.
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| Academic Significance and Societal Importance of the Research Achievements |
膠芽腫は治療経過中に脳内や脊髄にしばしば播種を起こして、治療困難となり、不良な転機をとることがしばしばある。播種を促進する因子は全く同定されておらず、播種の予測も困難である。今回STC1が播種を促進する因子であり、さらに播種を起こしやすい膠芽腫では髄液STC1濃度が高いことが明らかとなったので、事前に播種を予測できることが可能となった。STC1をターゲットとした治療薬も今後作成、検討する必要がある。膠芽腫の播種を予測・予防できれば、予後の改善も期待でき、臨床的意義は非常に高いものと思われる。
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