Abstract
Abstract Background: The growth of new blood vessels is regulated at multiple steps by interactions between several pro- and antiangiogenic factors. We believe that the angiogenesis induced by basic fibroblast growth factor (bFGF) is resistant to anti-VEGF/VEGFR (vascular endothelial growth factor/receptor) therapy. Methods: The Corneal Micro Pocket Assay was performed. 70 Charles River female C57BL/6 mice (age at start day, 6 weeks) were randomized to 7 arms (10 mice in each group): 1) bFGF; 2) VEGF-A; 3) bFGF negative, VEGF-A negative; 4) bFGF and sunitinib; 5) VEGF-A and sunitinib; 6) bFGF and bevacizumab; 7) VEGF-A and bevacizumab. Doses of bFGF, VEGF-A (R&D Systems), sunitinib (Pfizer), and bevacizumab (Roche) were 200 ng, 400 ng, 10 mg/kg, 50 mg/kg per animal, respectively. Hydron pellets preparation, surgical procedure, and quantification of angiogenesis (angiogenic score) were performed as previously reported (Kenyon BM et al.). Statistical significance was determined by the Student's t test. Results: There was no neovascularization in bFGF negative, VEGF-A negative group (mean, 0). The effect of 200 ng/pellet of bFGF (mean, 4.2; SEM, 0.05) was compared with that of 400 ng/pellet VEGF-A (mean, 4.08; SEM, 0.09), P=0.7. In bFGF-induced angiogenesis, sunitinib (mean, 3.9; SEM, 0.1; P=0.2) and bevacizumab (mean, 4.71; SEM, 0.33; P=0.85) did not impact on neovascularization in comparison with bFGF positive control. The angiogenic effect of VEGF-A was significantly inhibited by both sunitinib (mean, 0.38; SEM, 0.06; P=0.001) and bevacizumab (mean, 0.75; SEM, 0.05; P=0.001) in comparison with VEGF-A positive control. No significant differences between 2 targeted agents in bFGF and VEGF-A models were obtained. Conclusion: Our recent findings demonstrate that anti-VEGF(R) therapy significantly impacts on VEGF-A-induced angiogenesis and not on bFGF-induced neovascularization. Further studies are needed to assess the role of FGF-pathway in resistance to VEGF(R) therapy. The study was supported by Terry Fox Foundation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5157. doi:10.1158/1538-7445.AM2011-5157
Published Version
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