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.

Update on implications and mechanisms of angiogenesis in liver fibrosis

“…101 Bevacizumab has been approved by the US Food and Drug Administration for use in combination with 5-fluorouracil-based chemotherapy agents for the treatment of metastatic colorectal cancer in human patients, and the mechanism of action is related to inhibition of tumor angiogenesis. 102 Walker and his coworkers 103 also reported that bevacizumab can attenuate VEGF-induced angiogenesis and vascular malformations in the adult mouse brain. A more recent antiangiogenic approach has taken advantage of the multi-targeted tyrosine kinase receptor inhibitor sunitinib (SU11248).…”

“…Bevacizumab, a commercially available antiangiogenic agent that consists of a humanized monoclonal antibody against VEGF, can prevent the growth and maintenance of liver blood vessels and improve the degree of liver fibrosis . Bevacizumab has been approved by the US Food and Drug Administration for use in combination with 5‐fluorouracil‐based chemotherapy agents for the treatment of metastatic colorectal cancer in human patients, and the mechanism of action is related to inhibition of tumor angiogenesis . Walker and his coworkers also reported that bevacizumab can attenuate VEGF‐induced angiogenesis and vascular malformations in the adult mouse brain.…”

Role of traditional chinese medicine and its chemical components in anti-tumor metastasis

“…[30] Nowadays, compounds screened to inhibit tumor angiogenesis are provided with antitumor metastasis effects. Some models not only can be observed from histomorphology, [42] but also there are some neovascularization-related epithelial cell promoting factors, such as EGF, [43] VEGF, [44] FGF-2, [45] platelet-derived growth factor (PDGF), [46] platelet derived-endothelial cell growth factor-thymidine phosphorylase (PD-ECGF/TP) [47] and endothelin, [48] among which VEGF presents the most significant promoting effects on new vessels epithelial cells. [49] Normal epithelial cells can secrete these cell factors and so do some tumor cells.…”

Angiogenesis‐related gene expression profile in clinical cases of canine cancer

“…), and several therapies targeting tumour angiogenesis are being used for some tumour types (Scharf et al . ; Li et al . ).…”

“…In the field of veterinary oncology, the importance of angiogenesis in tumour progression has been recognised (Restucci et al 2003;Millanta et al 2006;Yonemaru et al 2006;Camacho et al 2014), and several therapies targeting tumour angiogenesis are being used for some tumour types (Scharf et al 2013;Li et al 2016). However, although several studies have reported on the expression of angiogenesisrelated genes in canine tumours, few studies have compared the expression profiles of angiogenesisrelated genes in normal and tumour tissues.…”