| Project/Area Number |
12671358
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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 | Kobe University Graduate School of Medicine |
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Principal Investigator |
SASAKI Masato Kobe University Neurosurgery assistant prof., 大学院・医学系研究科, 助手 (80314483)
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| Co-Investigator(Kenkyū-buntansha) |
HAYASHI Yoshitake Kobe University Neurosurgery Prof., 医学部, 教授 (50189669)
EHARA Kazumasa Kobe University Neurosurgery Associate Prof., 大学院・医学系研究科, 助教授 (20151996)
TAMAKI Norihiko Kobe University Neurosurgery Prof., 大学院・医学系研究科, 教授 (10030941)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2002: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2000: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | Malignant Gliomas / VEGF / Antisense / Anti-angiogenic Gene Therapy / 遺伝子治療 / ウイルス産生細胞 / RNA干渉 / siRNA / HIF-1 / デコイ |
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| Research Abstract |
With increasing size tumors are continually dependent on functional blood vessel system to guarantee the supply with oxygen and nutrients. VEGF is a key mediator not only of developmental but also of hypoxia-mediated and tumor-induced angiogenesis. Gene therapy using antisense VEGF with the aim to inhibit tumor angiogenesis may be a successful strategy for the treatment of highly vascular and invasive malignant gliomas. We investigated whether the blockage of VEGF/VEGFR paracrine loop may inhibit the tumor-angiogenesis. Several strategies, such as antisense VEGF, endothelial progenitor cells, HIF-1 decoy, siRNA, were adopted to block this pathway. Antisense VEGF introduced by retrovirus vectors showed a significant inhibition of VEGF expression, angiogenesis, tumor growth and prolongation of survival time without any serious adverse effects. Therefore, our study supports the concept that anti-angiogenic tumor therapy is a promising therapy for malignant gliomas.
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