title: Anti-VEGF antibody treatment of glioblastoma prolongs survival but results in increased vascular cooption.
abstract: Vascular endothelial growth factor (VEGF) is an important mediator of the intense angiogenesis which is characteristic of glioblastoma. While genetic manipulation of VEGF/VEGF receptor expression has previously been shown to inhibit glioblastoma growth, to date, no study has examined the efficacy of pharmacologic blockade of VEGF activity as a means to inhibit intracranial growth of human glioblastoma. Using intraperitoneal administration of a neutralizing anti-VEGF antibody, we demonstrate that inhibition of VEGF significantly prolongs survival in athymic rats inoculated in the basal ganglia with G55 human glioblastoma cells. Systemic anti-VEGF inhibition causes decreased tumor vascularity as well as a marked increase in tumor cell apoptosis in intracranial tumors. Although intracranial glioblastoma tumors grow more slowly as a consequence of anti-VEGF treatment, the histologic pattern of growth suggests that these tumors adapt to inhibition of angiogenesis by increased infiltration and cooption of the host vasculature.
authors.affiliation: Division of Hematology/Oncology, University of California, San Francisco, USA. jamesr@medicine.ucsf.edu
authors.forename: J L
authors.initials: JL
authors.lastname: Rubenstein
authors.forename: J
authors.initials: J
authors.lastname: Kim
authors.forename: T
authors.initials: T
authors.lastname: Ozawa
authors.forename: M
authors.initials: M
authors.lastname: Zhang
authors.forename: M
authors.initials: M
authors.lastname: Westphal
authors.forename: D F
authors.initials: DF
authors.lastname: Deen
authors.forename: M A
authors.initials: MA
authors.lastname: Shuman
mesh_terms: D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000098:blood supply* / Q000473:pathology / Q000628:therapy*; D016228:Endothelial Growth Factors / Q000037:antagonists & inhibitors* / Q000276:immunology; D005260:Female; D005909:Glioblastoma / Q000098:blood supply* / Q000473:pathology / Q000628:therapy*; D006801:Humans; D020287:In Situ Nick-End Labeling; D008222:Lymphokines / Q000037:antagonists & inhibitors* / Q000276:immunology; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D051381:Rats; D011923:Rats, Nude; D015996:Survival Rate; D013997:Time Factors; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D000906:Antibodies; D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors