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Publication Detail
Continuous local delivery of interferon-beta stabilizes tumor vasculature in an orthotopic glioblastoma xenograft resection model
  • Publication Type:
    Journal article
  • Publication Sub Type:
  • Authors:
    Denbo JW, Williams RF, Orr WS, Sims TL, Ng CY, Zhou J, Spence Y, Morton CL, Nathwani AC, Duntsch C, Pfeffer LM, Davidoff AM
  • Publication date:
  • Pagination:
    497, 504
  • Journal:
  • Volume:
  • Issue:
  • Keywords:
    administration & dosage, Animals, Biopsy,Needle, blood supply, Brain Neoplasms, Cerebrovascular Circulation, Disease Models,Animal, Disease Progression, drug therapy, Gene Transfer Techniques, Glioblastoma, Humans, Immunohistochemistry, Infusions,Intralesional, Interferon-beta, mortality, Neovascularization,Pathologic, pathology, prevention & control, Random Allocation, Rats, Reference Values, Survival Analysis, Transplantation,Heterologous, Xenograft Model Antitumor Assays
  • Author URL:
  • Notes:
    DA - 20110831 IS - 1532-7361 (Electronic) IS - 0039-6060 (Linking) LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't RN - 77238-31-4 (Interferon-beta) SB - AIM SB - IM
BACKGROUND: High-grade glioblastomas have immature, leaky tumor blood vessels that impede the efficacy of adjuvant therapy. We assessed the ability of human interferon (hIFN)-beta delivered locally via gene transfer to effect vascular stabilization in an orthotopic model of glioblastoma xenograft resection. METHODS: Xenografts were established by injecting 3 grade IV glioblastoma cell lines (GBM6-luc, MT330-luc, and SJG2-luc) into the cerebral cortex of nude rats. Tumors underwent subtotal resection, and then had gel foam containing an adeno-associated virus vector encoding either hIFN-beta or green fluorescence protein (control) placed in the resection cavity. The primary endpoint was stabilization of tumor vasculature, as evidenced by CD34, alpha-SMA, and CA IX staining. Overall survival was a secondary endpoint. RESULTS: hIFN-beta treatment altered the tumor vasculature of GBM6-luc and SJG2-luc xenografts, decreasing the density of endothelial cells, stabilizing vessels with pericytes, and decreasing tumor hypoxia. The mean survival for rats with these neoplasms was not improved, however. In rats with MT330-luc xenografts, hIFN-beta resulted in tumor regression with a 6-month survival of 55% (INF-beta group) and 9% (control group). CONCLUSION: The use of AAV hIFN-beta in our orthotopic model of glioblastoma resection stabilized tumor vasculature and improved survival in rats with MT330 xenografts
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