| Project/Area Number |
25861280
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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 |
Neurosurgery
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| Research Institution | Ehime University |
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Principal Investigator |
Inoue Akihiro 愛媛大学, 医学(系)研究科(研究院), 助教 (20593403)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2015: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2014: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2013: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
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| Keywords | 脳腫瘍学 / Oct-3/4 / cancer stem cell / 血管新生阻害剤 / in vivo 光イメージング / HIF-1α / VEGF / 腫瘍幹細胞 / 血管新生 |
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| Outline of Final Research Achievements |
In this study, we subcutaneously transplanted Oct-3/4-overexpressing human glioblastoma (U251/EGFP-Oct-3/4) cells into the right thighs of nude mice to evaluate the roles of Oct-3/4 in tumor angiogenesis. The conditioned media from U251/EGFP-Oct-3/4 cells significantly accelerated capillary-like tube formation compared with that of U251/EGFP cells. In comparison with U251/EGFP cells, U251/EGFP-Oct-3/4 cells had markedly elevated the expression of vascular endothelial growth factor mRNA under the control of hypoxia-inducible factor (HIF) 1α. In U251/EGFP-Oct-3/4 cells, enhanced protein expression and nuclear translocation of HIF1α were observed. Furthermore, we demonstrated that the involvement of AKT, an oncogenic signaling molecule, in the Oct-3/4 induced upregulation of HIF1α protein. Our findings suggest that Oct-3/4-expressing glioblastoma cells have the ability to adapt to low-oxygen environments within tumor masses by promoting tumor angiogenesis through AKT-HIF1 pathway.
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