Basic research of target the rapy of esophageal cancer using VEGF which is fused with biological active cytotoxic agents.

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Although many angiogenic inhibitors have been proposed, their side effects often make clinical application difficult. To minimize the side effects, we made a new angiogenic inhibitor which consists of only physiologically active materials. We have fused a pancreatic-type ribonuclease (RNase) gene to human basic fibroblast growth factor (bFGF), and studied the inhibitory effect of the fused protein on angiogenesis and tumor growth in vitro and in vivo. Inhibitory effects on in vitro angiogenesis were evaluated by an assay using fragments of human placental blood vessels (Brown, 1996). in an in vitro study, angiogenesis index calculated in wells with the fused protein was 9 % of the control and the fused protein inhibited angiogenesis dose dependently. In an in vivo study, A43 1 cells were injected into the subcutaneous layer of SCID mice and 1.45 mg of the fused protein was injected around the tumor every day for 3 weeks. The estimated tumor weight in the fused protein injection group was lighter than that in the control group. Effects of the fused protein on tumor growth was also observed. These results suggest that the RNase-FGF fused protein is a candidate for a new angiogenic inhibitorTo evaluate clinicopathological significance of angiogenesis and related peptide, we examined expression of VEGF and counted microvessel density on the sections of esophageal tumors. Both parameters were demonstrated to be useful prognostic markers.