FIG. 3.

Antitumor efficacy of 10⁷ PFU of antiangiogenic vaccinia virus in a nude mouse model. Subcutaneous 786-O tumors in nude mice (three mice per group; two tumors per mouse) were injected i.t. with 5 × 10⁶ PFU of vaccinia virus. (A) Tumor size was followed and plotted relative to the size before virus injection on day 1. All mice in the vvdd-VEGFR-1-Ig group were dead by day 9. (B) In another experiment nude mice were intravenously (i.v.) injected with 10⁷ PFU of vaccinia viruses, and tumor volumes were plotted relative to initial size. In the vvdd-VEGFR-1-Ig group, all mice were dead by day 9. (C) An additional four nude mice per group with or without tumors were injected intravenously with 10⁷ PFU of vvdd-VEGFR-1-Ig or vvdd-luc, and organs were harvested and hematoxylin-eosin stained after 3 days. Spleens of all virus-injected mice showed accumulations of small round-shaped, dark blue-stained cells, indicating extramedullary hematopoiesis. Large pictures are at 40× magnification, and small pictures in the upper left corner are at 63× magnification. Arrows indicate additional sites of extramedullary hematopoiesis. (D) Serum cytokine concentrations for MCP-1, IFN-γ, RANTES, KC, and MIP-1α were measured at the indicated time points. (E) VEGFR-1-Ig concentrations in serum of mice was assessed by ELISA. (F) Concentrations of TNF-α, IL-6, and MCP-1 were measured in serum of an additional three mice per group that were injected intravenously with different concentrations of vvdd-VEGFR-1-Ig. Bars indicate standard errors.