2004 Fiscal Year Final Research Report Summary
Anti-angiogenic therapy for malignant gliomas using hypoxia-responsive soluble VEGF receptor
| Project/Area Number |
14571299
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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 | University of Tsukuba |
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Principal Investigator |
TAKANO Shingo University of Tsukuba, Department of Neurosurgery, Institute of Clinical Medicine, Graduate School of Comprehensive Human Sciences, Associate Professor, 大学院・人間総合科学研究科, 助教授 (50292553)
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| Co-Investigator(Kenkyū-buntansha) |
SONE Hirohito University of Tsukuba, Graduate School of Comprehensive Human Sciences, Assistant Professor, 大学院・人間総合科学研究科, 講師 (30312846)
TSUBOI Koji University of Tsukuba, Graduate School of Comprehensive Human Sciences, Assistant Professor, 大学院・人間総合科学研究科, 講師 (90188615)
MITSUI Yoji University of Tokushima Bunnri, Department of Pharmacology, Professor, 香川薬学部, 教授
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| Project Period (FY) |
2002 – 2004
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| Keywords | glioma / VEGF / hypoxia inducible factor / angiogenesis / CPT-11 / metronomic chemotherapy / soluble VEGF receptor / Juzen Taiho To |
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| Research Abstract |
Soluble form of VEGF receptor, sFlt1 and hypoxia indutible factor(HIF) were focused on the key molecules of antiangiogenic therapy for malignant gliomas.
1.The role of sFlt1 and HIF in glioma tissues : The VEGF/sFlt1 ration over than 1 and high expression of HIF were bad prognostic factors in the patients with gliomas.
2.Anti-glioma effect of over expression of sFlt1 : sFlt1 gene transfection into U87 human malignant glioma cell lines resulted in 30% decrease of tumor volume compared to control.
3.Anti-angiogenic effect of CPT-11 : CPT-11 had potent angiosuppressive agent by inhibiting HIF and VEGF expression of glioma cells and inhibiting endothelial cell proliferation and tube formation.
4.The effect of metronomic schedule of CPT-11 for glioma growth : Low dose (1mg/kg) and long term (77 days) administration of CPT-11 resulted in glioma growth which was similar to moderate dose (40mg/kg) and short term (10 days) administration without systemic side effect.
5.JTT treatment caused to not only enhance immune function but also inhibit angiogenesis in mouse bearing glioma.
Metronomic chemotherapy using CPT-11 is effective for glioma growth by inhibiting HIF and VEGF expression and by inhibiting endothelial cell proliferation and tube formation. sFlt1 and JTT are also candidates as angiosuppressive agent for glioma.
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