Combining cercosporamide and Ara-C suppresses growth of MV4-11 AML xenograft tumors. (A) Tumor-bearing mice were randomized to treatment groups and dosed daily with 20 mg/kg Ara-C, or with cercosporamide (20 mg/kg daily or 10 mg/kg twice daily), or with Ara-C in combination with either cercosporamide treatment. The vehicle-treated mice (captisol for cercosporamide and water for Ara-C) are shown. Relative tumor volumes measured by caliper are plotted at each time point divided by initial tumor volume for each animal (T₁/T₀) ± standard error of the mean. All treatments showed statistically significant activity when compared with the appropriate vehicle-treated controls* (cercosporamide 10 mg/kg twice daily, P < .011; cercosporamide 20 mg/kg daily, P < .006; Ara-C, P < .0374; cercosporamide 10 mg/kg twice daily plus Ara-C vs either vehicle, P < .0001). Cercosporamide 10 mg/kg twice daily plus Ara-C was also significantly more effective than cercosporamide (P < .0009**) or Ara-C alone (P = .0005**). Data are representative of 4 separate xenograft studies. (B) Body weight distribution across all treatment groups was calculated by normalizing body weight for each animal at the end of study (day 42) (W_I) with that immediately prior to treatment (W₀). (C) Western blot analyses for p-eIF4E were run on tumor lysates harvested at the end of study. Cell lysates for the indicated treatment conditions were analyzed by SDS-PAGE and immunoblotted with an antibody against the phosphorylated form of eIF4E (upper panel). Equal amounts of lysates from the same experiment shown in the upper panel were analyzed separately by SDS-PAGE and immunoblotted with an antibody against eIF4E (middle panel). The same blot shown in the middle panel was immunoblotted with an anti-actin antibody, as indicated (lower panel). Each lane represents an individual tumor. mpk, mg/kg.