Figure 4. Localization of rhASM in subcutaneous tumors and livers.

(A) ASM activity in tumor extracts of rhASM/sorafenib treated mice was significantly higher (ANOVA, df (2,30), F = 22.58, p<0.001; Dunnett's post hoc test p<0.001) than control, while sorafenib had no effect on baseline ASM activity. (B) ASM activity in liver extracts of rhASM/sorafenib treated mice also was higher than vehicle treated mice (ANOVA, df (2,30), F = 11.17, p<0.001; Dunnett's post hoc test p<0.001), and sorafenib had no effect on baseline ASM activity. Of note, animals in the combination treatment group had >12 times higher ASM activity in livers than in tumors, demonstrating the hepatotropic nature of rhASM during chronic administration and relatively modest distribution to the subcutaneous tumors. ** p<0.001. Note: Y-axes activity (10⁻⁶ mol/L/hour) was measured in equal parts of 20% weight/volume tissue extracts as described in Materials and Methods.