Figure 2.
Effects of Smo and/or Pi3k inhibition on in vivo growth of Ptch mutant ERMS. Analysis of RMS of Ptch+/− mice that have been treated orally for 21 (vismodegib and/or pictilisib n = 27; sonidegib and/or pictilisib n = 27) or 35 days (HhAntag and/or pictilisib n = 22) as indicated. (A) Disease progression was classified according to RECIST criteria as progressive disease (PD), stable disease (PD) or partial response (PR). Right panel shows individual changes in tumor growth as measured by microCT at therapy end in comparison to the tumor size at therapy onset. (B) Quantification of Ki67 positive cells of tumors shown in A). (C) Gli1 and Hhip expression in tumor samples collected at day 21 (vismodegib and/or pictilisib study or sonidegib and/or pictilisib study) or day 14 (HhAntag and/or pictilisib study; see main text for explanation). (D) Correlation of tumor growth changes that have been treated with SMO inhibitors with Gli1 expression. (E) pAkt normalized to Akt expression levels as measured by semiquantitative densitometry of Western blot (Western blots and pAkt and Akt expression levels are shown in Supplementary Figures S3C,D, respectively). * P < 0.05, **P < 0.01, ***P < 0.001 when analyzed by Dunn's test for multiple comparisons.