Figure 5From: Spatial morphological and molecular differences within solid tumors may contribute to the failure of vascular disruptive agent treatments Changes in endothelial cells and vessel morphology 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 after treatment. Formalin fixed liver sections were stained with anti-CD34 antibody to visualize tumor vessels. (A), Control tumor, arrow indicates a patent tumor vessel; 1hr OXi4503, arrows indicate endothelial cells rounding up and detaching from the vessel basement membrane; 1hr OXi4503, EC apoptosis, the section was doubly immunostained for CD34 and active caspase-3 (apoptosis marker), to visualise endothelial cells undergoing apoptosis (arrows); 24hrs OXi4503 center, arrow points at a totally occluded tumor vessel; 24hrs OXi4503 periphery, arrow indicates patent tumor vessel; 5 days OXi4503 , center, demonstrating regenerating tumor vessels surrounded by proliferating tumor cells; Single staining magnification scale bar=50μm, double staining magnification scale bar=25μm. (B), Enumeration of vascular endothelial cell apoptosis show significant differences between the tumor center and periphery at one and 24 hours after treatment (*P <0.001); (C), Quantification of tumor vascular changes following OXi4503 treatment. Vascular density decreased significantly in the tumor center (**P<0.0001), but not the periphery (P=0.173) at 24 hours after treatment. Tumor revascularization at day five is significantly higher compared to the untreated control both at tumor center and the periphery (*P=0.001). Results are mean values ± SEM, (n≥5). Black bars = tumor periphery, Grey bars = tumor center.Back to article page