Figure 2.

Effects of several vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) antagonists on adenovirus expressing VEGF-A (Ad-VEGF-A¹⁶⁴)–induced mother vessels (MV). Five days after Ad-VEGF-A¹⁶⁴ ear injection, nude mice were treated with single treatments of the following: phosphate-buffered saline (PBS) (A); G6 (20 mg/kg), an antibody against VEGF-A (B); DC101 (40 mg/kg), an antibody against VEGFR-2 (C); sunitinib (50 mg/kg), a tyrosine kinase inhibitor with activity against VEGFR-2 (D); MF1 (40 mg/kg), an antibody against VEGFR-1 (E). The boxed area in A indicates MV field and is shown at higher magnification in the bottom panel. Sunitinib was given by gavage, the other drugs were given i.p. Ears were taken for histologic examination 24 hours later. G6, DC101, and sunitinib all induced MV collapse to glomeruloid microvascular proliferations (GMP), similar to that induced by aflibercept, whereas MV persisted in mice treated with PBS and MF1. Note reduction in edema indicated by yellow double-headed arrows, indicating ear thickness in untreated control (A) versus G6-treated (B) mice. White arrows indicate MV in A, the top panel in B, and E. Dashed lines indicate well developed GMP (B, C, and D). Scale bars: 100 μm (A and B, top panel); 50 μm (B, bottom panel and C–E).