Figure 4.

Post tumor formation therapy in control animals. (a) Timeline of experiments of NVP-BHG 712, Ephrin-B2-Fc and Placebo IGG-Fc / PEG 300 treatment in efnb2^lox/lox control mice (BLM = Bioluminescence measurements, MRI = Magnetic resonance imaging, IF = Immunofluorescence, LA = Luciferase assay) (b) Animals treated with NVP-BHG 712 showed significantly earlier signs of neurologic symptoms when compared with the placebo group (median NVP-BHG 712: 23 days, n = 7, p = 0.035, Log-rank (Mantel–Cox) test). Significance threshold adjusted for multiple comparisons by Bonferroni method. (c) Number of spinal metastases was unaffected by applying therapeutics. Mean individual and total tumor volume was also unaffected by therapy. Mean ± SEM for all experiments shown. (d) No significant proliferation differences were observed under post-tumor treatment in efnb2^lox/lox mice. Statistically significant increase in the number of tumor blood vessels of Ephrin-B2-Fc treated group (n = 7, 5, respectively, p = 0.023) and size of tumor blood vessels (n = 6, p = 0.008 (one-way ANOVA with Dunnett’s multiple comparison test)). (e) Representative images of confocal microscopy in spinal metastatic tumors. Staining and treatment as indicated. Mean ± SEM for all experiments shown. One star (*) indicates p ≤ 0.05, two stars (**) indicate p ≤ 0.01 and three stars (***) indicate p ≤ 0.001.