1999 Fiscal Year Final Research Report Summary
Cloning of the genes related for the angiogenesis of malignant glioma
| Project/Area Number |
10671307
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | Saga Medical School |
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Principal Investigator |
FUKUYAMA Kouzou Saga Medical School, Assistant Professor, 医学部, 講師 (60238516)
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| Co-Investigator(Kenkyū-buntansha) |
TODA Keisuke Saga Medical School, Assistant Professor, 医学部, 助手 (80274588)
MINETA Toshihiro Saga Medical School, Assistant, 医学部, 助手 (20264187)
TABUCHI Kazuo Saga Medical School, Professor, 医学部, 教授 (50116480)
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| Project Period (FY) |
1998 – 1999
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| Keywords | glioma / angiogenesis / PD-ECGF / hypoxia / VEGF / Ets-1 |
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| Research Abstract |
Angiogenesis plays an important role in the growth and metastasis of tumors. Platelet-derived endothelial cell growth factor (PD-ECGF) is known to be chemotactic for endothelial cells in vitro and angiogenic in vivo. Immunohistochemical analysis of PD-ECGF was carried in fifty-two cases of gliomas (36 glioblastomas and 16 anaplastic astrocytomas). The expression of PD-ECGF was compared with CD31, SMA, HAM56 and CD68. The PD-ECGF positive cells were observed around the blood vessels and in the stromal macrophage in 11 glioblastomas and one anaplastic astrocytoma. The expression of PD-ECGF by macrophages was closely correlated with the degree of stromal vascularity in glioma. The cases highly expressed PD-ECGF were associated with unfavorable clinical courses.
The expression of PD-ECGF was induced by hypoxic environment in cultured endothelial and glioma cells. The 5' promoter region of PD-ECGF gene is consisted of the responsive elements for p300, Ets, and HSF. These transcription factors are induced by ischemic stimuli, especially hypoxia induced Ets-1 is known to upregulate VEGF-R expression. Hypoxia mediated Ets-1 induction seems to be develop glioma angiogenesis both through VEGF pathway and PD-ECGF pathway.
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