Effect of bevacizumab on angiogenesis and growth of canine osteosarcoma cells xenografted in athymic mice

Valery F. Scharf Department of Small Animal Clinical Sciences, College of Veterinary Medicine, College of Medicine, University of Florida, Gainesville, FL 32608.

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James P. Farese Department of Small Animal Clinical Sciences, College of Veterinary Medicine, College of Medicine, University of Florida, Gainesville, FL 32608.

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Alastair R. Coomer Department of Small Animal Clinical Sciences, College of Veterinary Medicine, College of Medicine, University of Florida, Gainesville, FL 32608.

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Rowan J. Milner Department of Small Animal Clinical Sciences, College of Veterinary Medicine, College of Medicine, University of Florida, Gainesville, FL 32608.

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David P. Taylor Department of Infectious Diseases and Pathology, College of Veterinary Medicine, College of Medicine, University of Florida, Gainesville, FL 32608.

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Marc E. Salute Department of Small Animal Clinical Sciences, College of Veterinary Medicine, College of Medicine, University of Florida, Gainesville, FL 32608.

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Myron N. Chang Department of Epidemiology and Health Policy Research, College of Medicine, University of Florida, Gainesville, FL 32608.

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Dan Neal Department of Epidemiology and Health Policy Research, College of Medicine, University of Florida, Gainesville, FL 32608.

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Dietmar W. Siemann Department of Radiation Oncology, College of Medicine, University of Florida, Gainesville, FL 32608.

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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.

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.

Contributor Notes

Dr. Farese's present address is VCA Animal Care Center of Sonoma County, 6470 Redwood Dr, Rohnert Park, CA 94928.

Dr. Coomer's present address is Veterinary Specialist Group, 97 Carrington Rd, Mt Albert 1003, New Zealand.

Dr. Taylor's present address is Vetnostics Laverty Pathology, 60 Waterloo Rd, North Ryde, NSW 2113, Australia.

Supported by Varian Medical Systems, the University of Florida Mark S. Bloomberg Residency Research Fund, and in part by a grant from the National Institutes of Health (R01CA089655).

Presented as a poster presentation at the Veterinary Cancer Society Symposium, Pine Mountain, Ga, October 2006.

Address correspondence to Dr. Farese (faresej@gmail.com).
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