2000 Fiscal Year Final Research Report Summary
Expression of VEGF and anti-tumor effect of antisense oligomer in malignant glioma
| Project/Area Number |
11671361
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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 | Fukui Medical University |
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Principal Investigator |
KUBOTA Toshihiko Department of Neurosurgery Fukui Medical University Professor, 医学部, 教授 (70092781)
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| Co-Investigator(Kenkyū-buntansha) |
KITAI Ryuhei Department of Neurosurgery Fukui Medical University Assistant, 医学部, 助手 (80251990)
SATO Kazufumi Department of Neurosurgery Fukui Medical University Lecturer, 医学部・附属病院, 講師 (60187177)
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| Project Period (FY) |
1999 – 2000
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| Keywords | Glioma / VEGF / Flk-1 / Angiogenesis / Brain edema / Prognosis |
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| Research Abstract |
To identify early prognostic markers may aid in the clinical management of tumor patients. VEGF is regarded as the central mediator of angiogenesis and a potent inducer of vascular permeability. This unique bifunctional properties of VEGF in tumor biology suggest that it may be a reliable prognostic marker. We immunohistochemically examined expressions of VEGF and its corresponding receptors Fit-1 and Flk-1 in a series of 50 astrocytic tumors, and correlated their expressions with angiogenesis, brain edema and prognosis. There were significant relationships between VEGF, Flk-1 expressions and glioma malignancy grading, intratumoral vascularity and peritumoral brain edema, respectively. VEGF and Flk-1 were significant prognostic factors within each tumor grade, which had a negative impact on overall survival. Additionally, overexpression of VEGF and Flk-1 were significantly associated with earlier recurrence in low grade astrocytomas. We designed a 20 mer antisense VEGF oligomer, which significantly decreased VEGF mRNA and protein production, but had no effect on the growth of T98G cells in vitro. These findings suggest that VEGF facilitates glioma growth via promotting angiogenesis. It is possible to subcategorize each grade of astrocytic tumors based on their VEGF and Flk-1 staining pattern, which may be crucial in predicting the biological behavior of tumors and thus provide useful information with regard to adequate treatment. Inhibition of VEGF action at multiple levels may therefore be a potent strategy for glioma therapy. A further evaluation of in vivo anti-tumor effect of antisense VEGF is needed.
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