Dynamics and Biological Significance of Vascular Growth Factors in Urogenital Cancers.

在泌尿生殖道肿瘤中评估肿瘤血管生成和血管生成因子之间的关系。VEGF基因在半数以上的肾细胞癌中过表达。VEGF基因表达水平与肿瘤微血管密度显著相关。免疫组化显示肾细胞癌细胞浆VEGF染色呈阳性。VEGF基因在40%的乳腺癌中过表达。VEGF在膀胱癌细胞中呈明显阳性表达。VEGF受体基因表达与VEGF基因表达水平一致。因此，肾细胞癌和膀胱癌的血管生成可能是通过VEGF及其受体的旁分泌机制来促进的。本研究对肾细胞癌中VEGF-A、B、C和D的表达进行了研究，发现VEGF-A及其受体VEGFR-1和VEGFR-2在肾细胞癌的血管生成中起重要作用，而VEGF-B和VEGF-C在肾细胞癌的血管生成中作用不大。我们比较了癌症患者和健康对照者的血清VEGF水平。肾细胞癌患者血清VEGF水平明显高于健康对照组。术后血清VEGF水平较术前明显下降。血清VEGF水平与肿瘤体积、转移和分期显著相关。膀胱癌患者组的平均血清VEGF水平也高于健康对照组。因此，我们认为肾细胞癌和膀胱癌均存在VEGF的释放，血清VEGF水平可作为肾细胞癌和膀胱癌恶性潜能的一个指标，为研制抗血管生成因子抗体，用于肾细胞癌和膀胱癌的诊断和治疗提供了基础资料。

The relationship between tumor angiogenesis and angiogenic factors was evaluated in urogenital cancers. VEGF gene was overexpressed in more than a half of renal cell carcinoma (RCC). The expression level of VEGF genes was significantly correlated with the intratumoral microvessel density. An immunohistologic analysis revealed that cytoplasm of RCC appeared to be positive for the VEGF staining. VEGF gene was also overexpressed in 40% of BCas. At protein level, VEGF was apparently positive in bladder carcinoma cells. VEGF-receptor genes were expressed in concordance with the VEGF gene expression level in both tumors. Thus, angiogenesis in RCC and bladder cancer is suggested to be facilitated by a paracrine mechanism with VEGF and its receptors.We studied the expression of VEGF-relating genes (VEGF-A, B, C, and D) in RCCs and found that VEGF-A and the receptors, VEGFR-1 and VEGFR-2, play crucial roles in the angiogenesis of RCC while VEGF-B and VEGF-C do little.Based on the above results, we compared serum VEGF levels between cancer patients and healthy control subjects. The mean serum VEGF level was higher in the RCC patient group than in the healthy control group. Postoperative serum VEGF level apparently decreased as compared with the preoperative level. Serum VEGF level was significantly correlated with tumor volume, metastasis, and stage. The mean serum VEGF level was also higher in the bladder cancer patient group than in the healthy control group. Thus we suggest that RCC and bladder cancer release VEGF into the blood circulation and serum VEGF level would be a marker of malignant potential of these tumors.Taken together, these results would be useful as basic data for the development of antiangiogenic-factor antibody facilitating diagnosis and therapy of RCC and bladder cancer.