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

虽然已经提出了许多血管生成抑制剂，但它们的副作用往往使临床应用困难。为了将副作用降到最低，我们研制了一种新的血管生成抑制剂，它只包含生理活性物质。我们将胰型核糖核酸酶(RNase)基因与人碱性成纤维细胞生长因子(BFGF)融合，研究了融合蛋白在体内外对血管生成和肿瘤生长的抑制作用。通过使用人胎盘血管片段的检测来评估对体外血管生成的抑制作用(Brown，1996)。在体外研究中，用融合蛋白计算的血管生成指数是对照的9%，融合蛋白抑制血管生成的作用呈剂量依赖关系。在体内研究中，将A431细胞注射到SCID小鼠皮下，每天在肿瘤周围注射1.45 mg融合蛋白，连续3周。融合蛋白注射组的肿瘤重量明显轻于对照组。同时观察融合蛋白对肿瘤生长的影响。为探讨血管生成及相关多肽的临床病理意义，我们在食管瘤切片上检测了血管内皮生长因子的表达，并对微血管密度进行了计数。这两个参数都被证明是有用的预后标志。

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.