Figure 6

Changes in tumor kinetics following OXi4503 treatment. Mice were treated with a single IP dose of OXi4503 (100mg/kg) at 16 days after tumor induction. Tissues were collected at one hour, 24 hours and five days following OXi4503 treatment. (A). H&E stained sections at indicated times after OXi4503 treatment. Magnification scale bar=200μm. Tumor cells at the live rim at one and 24hrs are seen in the enclosed lined areas indicated by arrows. NA= necrotic/apoptotic area, T= tumor, L=liver. (B) Tumor cell apoptosis at indicated times after treatment detected by active caspase-3 staining. Low magnification scale bar=250μm, inset magnification scale bar=50μm. Graph showing quantification of apoptotic tumor cells. Results are mean values ± SEM, (n≥5). Black bars = tumor periphery, Grey bars = tumor center. Apoptosis in the treated tumor periphery was significantly higher than in the periphery of control tumors at one and 24 hours (*P <0.001) but significantly lower than the center of the treated tumors (#P<0.0001). (C) Proliferation changes in tumors at indicated times after treatment detected by Ki-67 staining. Low magnification scale bar=250μm, inset magnification scale bar=50μm. Graph showing quantification of Ki-67 positive tumor cells. Results are mean values ± SEM, (n≥5). Black bars = tumor periphery, Grey bars = tumor center. Proliferation in the periphery was significantly reduced at one and 24 hours (*P <0.001) following treatment compared to controls. Significantly higher number of cells proliferate in the periphery of treated tumors compared to the center (#P<0.0001).