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Expression of VEGF and anti-tumor effect of antisense oligomer in malignant glioma

Research Project

Project/Area Number 11671361
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionFukui Medical University

Principal Investigator

KUBOTA Toshihiko  Department of Neurosurgery Fukui Medical University Professor, 医学部, 教授 (70092781)

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)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsGlioma / VEGF / Flk-1 / Angiogenesis / Brain edema / Prognosis / antisense / oligomer
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.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (6 results)

All Other

All Publications (6 results)

  • [Publications] 久保田紀彦: "Prognostic value of VEGF and receptors in human glioma"Brain Pathology. Vol.10. 734 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yongxue Yao: "Prognostic value of vascular endothelial growth factor and its receptors flt-1 and flk-1 in astrocytic tumours"Acta Neurochirurgica. (in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Toshihiko Kubota: "Prognostic value of VEGF and receptors in human glioma"Brain Pathology. Vol.10. 734 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yongxue Yao: "Prognostic value of vascular endothelial growth factor and its receptors flt-1 and flk-1 in astrocytic tumours"Acta Neurochirurgica. (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 久保田紀彦: "Prognostic value of VEGF and receptors in human glioma"Brain Pathology . Vol.10 No.4. 734 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yongxue Yao: "Prognostic value of vascular endothelial growth factor and its receptors flt-1 and flk-1 in astrocytic tumours"Acta Neurochirurgica. (in press). (2001)

    • Related Report
      2000 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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