title: Effect of bevacizumab on angiogenesis and growth of canine osteosarcoma cells xenografted in athymic mice.
abstract: Objective-To investigate the effects of bevacizumab, a human monoclonal antibody against vascular endothelial growth factor, on the angiogenesis and growth of canine osteosarcoma cells xenografted in mice. Animals-27 athymic nude mice. Procedures-To each mouse, highly metastasizing parent osteosarcoma cells of canine origin were injected into the left gastrocnemius muscle. Each mouse was then randomly allocated to 1 of 3 treatment groups: high-dose bevacizumab (4 mg/kg, IP), low-dose bevacizumab (2 mg/kg, IP), or control (no treatment). Tumor growth (the number of days required for the tumor to grow from 8 to 13 mm), vasculature, histomorphology, necrosis, and pulmonary metastasis were evaluated. Results-Mice in the high-dose bevacizumab group had significantly delayed tumor growth (mean ± SD, 13.4 ± 3.8 days; range, 9 to 21 days), compared with that for mice in the low-dose bevacizumab group (mean ± SD, 9.4 ± 1.5 days; range, 7 to 11 days) or control group (mean ± SD, 7. 2 ± 1.5 days; range, 4 to 9 days). Mice in the low-dose bevacizumab group also had significantly delayed tumor growth, compared with that for mice in the control group. Conclusions and Clinical Relevance-Results indicated that bevacizumab inhibited growth of canine osteosarcoma cells xenografted in mice, which suggested that vascular endothelial growth factor inhibitors may be clinically useful for the treatment of osteosarcoma in dogs. Impact for Human Medicine-Canine osteosarcoma is used as a research model for human osteosarcoma; therefore, bevacizumab may be clinically beneficial for the treatment of osteosarcoma in humans.
authors.affiliation: Department of Small Animal Clinical Sciences, College of Veterinary Medicine, College of Medicine, University of Florida, Gainesville, FL 32608, USA.
authors.forename: Valery F
authors.initials: VF
authors.lastname: Scharf
authors.forename: James P
authors.initials: JP
authors.lastname: Farese
authors.forename: Alastair R
authors.initials: AR
authors.lastname: Coomer
authors.forename: Rowan J
authors.initials: RJ
authors.lastname: Milner
authors.forename: David P
authors.initials: DP
authors.lastname: Taylor
authors.forename: Marc E
authors.initials: ME
authors.lastname: Salute
authors.forename: Myron N
authors.initials: MN
authors.lastname: Chang
authors.forename: Dan
authors.initials: D
authors.lastname: Neal
authors.forename: Dietmar W
authors.initials: DW
authors.lastname: Siemann
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000627:therapeutic use*; D000068258:Bevacizumab; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D012516:Osteosarcoma / Q000098:blood supply*
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab