1a: In vivo tumor response of A375(DRO) xenograft tumors. 5 × 106 A375(DRO) cells were injected s.c. and tumors were allowed to grow for 3.5 wk after tumor establishment (~100 mm3). After estblishment, treatment conditions were (A) control, (B) 30 mg/kg/d LGD1069, and (C) 10 mg/kg/d ROSI and (D) combination of 30 mg/kg/day LGD1069 and 10 mg/kg/day ROSI. Tumors were measured twice per week. Points, mean tumor volume/group; bars, SEM. One Way ANOVA – Kruskal-Wallis test was used to assess the significance of the difference of tumor sizes at the end of the experiment (*P = 0.002). 1b: representative control tumor showing approximately 20% necrosis (*). Marked cellular vacuolization is seen in the non-necrotic tissue. Hematoxyline and Eosin staining 2× magnification. 1c: An enlarged picture from the control tumor showing the junction of the necrotic (*) and the viable, yet markedly vacuolated melanoma cells. Hematoxyline and Eosin staining. 40× magnification. 1d: A representative Rosi treated tumor with > 70% necrosis (edged by arrows) of the total tissue volume with a small rim of viable tumor. Hematoxyline and Eosin staining 2× magnification.