title: Continuous local delivery of interferon-β stabilizes tumor vasculature in an orthotopic glioblastoma xenograft resection model.
abstract: 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)-β 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-β or green fluorescence protein (control) placed in the resection cavity. The primary endpoint was stabilization of tumor vasculature, as evidenced by CD34, α-SMA, and CA IX staining. Overall survival was a secondary endpoint.
  
  
  RESULTS
  hIFN-β 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-β resulted in tumor regression with a 6-month survival of 55% (INF-β group) and 9% (control group).
  
  
  CONCLUSIONS
  The use of AAV hIFN-β in our orthotopic model of glioblastoma resection stabilized tumor vasculature and improved survival in rats with MT330 xenografts.
authors: Department of Surgery, St. Jude Children's Research Hospital, Memphis, TN; Department of Surgery, University of Tennessee Health Science Center, Memphis, TN, USA.
authors: Jason W
authors: JW
authors: Denbo
authors: Regan F
authors: RF
authors: Williams
authors: W Shannon
authors: WS
authors: Orr
authors: Thomas L
authors: TL
authors: Sims
authors: Catherine Y
authors: CY
authors: Ng
authors: Junfang
authors: J
authors: Zhou
authors: Yunyu
authors: Y
authors: Spence
authors: Christopher L
authors: CL
authors: Morton
authors: Amit C
authors: AC
authors: Nathwani
authors: Christopher
authors: C
authors: Duntsch
authors: Lawrence M
authors: LM
authors: Pfeffer
authors: Andrew M
authors: AM
authors: Davidoff
mesh_terms: D000818:Animals; D001707:Biopsy, Needle; D001932:Brain Neoplasms / Q000098:blood supply* / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002560:Cerebrovascular Circulation; D004195:Disease Models, Animal; D018450:Disease Progression; D018014:Gene Transfer Techniques; D005909:Glioblastoma / Q000098:blood supply* / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D036502:Infusions, Intralesional; D016899:Interferon-beta / Q000008:administration & dosage*; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D011897:Random Allocation; D051381:Rats; D012016:Reference Values; D016019:Survival Analysis; D014183:Transplantation, Heterologous; D023041:Xenograft Model Antitumor Assays
chemical_list: D016899:Interferon-beta