1. Treatment with NVP-AEW541 shows no efficacy in an s. c
Treatment with NVP-AEW541 shows no efficacy in an s.c. xenograft Wilms tumor model.
Treatment with NVP-AEW541 shows no efficacy in an s.c. xenograft Wilms tumor model. (A) Tumor volumes in mice implanted with WiT49 cells s.c. and treated with 25 mg/kg, 50 mg/kg, or 75 mg/kg for 15 d. Tumor volume is plotted as percentage of day 0 for all groups, with no statistically significant differences compared with vehicle-treated controls. (B) Final tumor weights for the same experiment also show no differences between treated and untreated groups. (C) Pharmacodynamic biomarkers assessed in the WiT49 s.c. model after treatment with NVP-EW541. Although a dose-dependent decrease in phospho-IGF1R and, to a lesser extent, phospho-IRS1 were observed, no significant inhibition of the downstream PI3 and MAP kinase pathways was seen. (D) Histology of the s.c. WiT49 model. The cells had prominent nucleoli and abundant slightly eosinophilic cytoplasm, with a morphological appearance more closely resembling malignant rhabdoid tumors of the kidney than classic Wilms tumors. [Original magnification of ×100 (inset, magnification of ×400).]
Aleksandra Bielen et al. PNAS 2012;109:20:E1267-E1276
©2012 by National Academy of Sciences