Figure 1.
Correlation between dose-dependent treatment efficacy and reduction in viable CEPs in various tumor models. Tumor growth delays or tumor volumes at the end of treatment. (A) MeWo human melanoma treated with CTX administered through drinking water on a daily basis. (B) MDA-MB-231/MVB9 human breast cancer–derived multidrug-resistant variant tumors treated with Vbl, injected intraperitoneally 3 times a week. (C) MDA-MB-231/LM2-4 human breast cancer treated with Nvb administered by gavage 3 times a week, at the indicated doses. In addition, 4-week-old erythroleukemic mice were treated with either (D, F) CTX through drinking water or (E, G) CDDP by intraperitoneal injection twice a week; tumor growth in this model is represented by reduction in hematocrit levels and changes in spleen volume at end point. For both drugs, groups are designated as follows: control untreated (•), 10 mg/kg CTX daily or 0.5 mg/kg CDDP (○), 20 mg/kg CTX daily or 1 mg/kg CDDP (▪), 50 mg/kg CTX daily or 2 mg/kg CDDP (□) and 3 mg/kg CDDP (♦). Parallel experiments were performed to test for viable CEPs by flow cytometry, as previously described6 (H-L). Black columns represent the optimal therapeutic doses in each case that induce the most significant decline in viable CEP levels and a reduction in tumor volumes, with minimal or no toxicity, as summarized in Table 1. Significant differences from control: *P > .05; **.05>P > .01; and *** P < .01.