Fig. 4.
Effect of combined B20 and LY2157299 treatment in SMA-497 and GL-261 syngeneic models in vivo. Syngeneic mice were intracranially implanted with SMA-497 or GL-261 cells and treated twice weekly with 5 mg/kg B20 or daily with 150 mg/kg LY2157299 or corresponding solvents or both from day 7 on. Brain sections from SMA-497 (early-stage) and GL-261 (early- and end-stage) were studied. (A) Tumor volumes and (B) CD31+ capillaries. (C) pSMAD2. (D) CA 9+ areas (*P < .05, **P < .01, ***P < .001, one-way ANOVA followed by Tukey's post hoc test 95% CI, treated vs solvent, +++P < .001, B20 + LY2157299 vs B20, ##P < .01, B20 + LY2157299 vs LY2157299). (E) Kaplan–Meier survival curves (Gehan-Breslow-Wilcoxon test, considered significant for P < .05). (F) Gene cluster analysis. Functional interactions between TGFβ1/2 and genes upregulated in angiogenic profiles in SMA-497 (left) and GL-261 (right) were analyzed in Affymetrix microarray-based gene expression profiling by STRING analysis. Interactions with high confidence score of 0.700 were integrated into the interactome. Clusters were determined by Markov cluster algorithm and presented with different node colors. Intercluster edges are represented by dashed lines. hpf, high-powered field; PBS, phophate buffered saline.