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

泌尿生殖癌中血管生长因子的动力学和生物学意义。

• 批准号: 10470330
• 负责人: KATO Tetsuro
• 金额: $ 8.32万
• 依托单位: Akita University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-10470330/
• 关键词: angiogenic factor; urogenital cancer; VEGF; bFGF; ELISA; angiogenesis; 腎細胞癌; VEGF受容体; 遺伝子発現; 定量的PCR

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.

评价了泌尿生殖系统肿瘤血管生成与血管生成因子的关系。VEGF基因在半数以上的肾细胞癌（RCC）中过表达。VEGF基因表达水平与肿瘤内微血管密度显著相关。免疫组织学分析显示，RCC细胞质中VEGF染色呈阳性。VEGF基因在40%的bca中也过表达。在蛋白水平上，VEGF在膀胱癌细胞中呈明显阳性。VEGF受体基因在两种肿瘤中的表达均与VEGF基因表达水平一致。因此，RCC和膀胱癌的血管生成可能是由VEGF及其受体的旁分泌机制促进的。我们研究了vegf相关基因（VEGF-A、B、C和D）在RCC中的表达，发现VEGF-A及其受体VEGFR-1和VEGFR-2在RCC血管生成中起关键作用，而VEGF-B和VEGF-C作用不大。基于以上结果，我们比较了肿瘤患者与健康对照者的血清VEGF水平。RCC患者组平均血清VEGF水平高于健康对照组。术后血清VEGF水平较术前明显降低。血清VEGF水平与肿瘤体积、转移及分期有显著相关性。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RCC和膀胱癌释放VEGF进入血液循环，血清VEGF水平可能是这些肿瘤恶性潜能的标志。这些结果将为抗血管生成因子抗体的开发提供基础数据，促进RCC和膀胱癌的诊断和治疗。

项目成果

小倉泰伸、他: "表在性膀胱癌における血管新生因子の発現と腫瘍血管密度に関する免疫組織学的検討" 日本泌尿器科学会雑誌. 80(5). 529-537 (1998)

Yasunobu Ogura 等人：“浅表性膀胱癌中血管生成因子表达和肿瘤血管密度的免疫组织学研究”日本泌尿外科协会杂志 80(5) (1998)。

Sato K, et al.: "Expression of vascular endothelial growth factor gene and its receptor (flt-1) gene in urinary bladder cancer." Tohoku J Exp Med. 185(3). 173-184 (1998)

Sato K 等人：“血管内皮生长因子基因及其受体 (flt-1) 基因在膀胱癌中的表达”。

Sato K et al.: "Expression of vascular endothelial growth factor gene and its receptor (flt-1) gene in urinary bladder cancer."Tohoku J Exp Med. 185. 173-184 (1998)

Sato K等：“血管内皮生长因子基因及其受体（flt-1）基因在膀胱癌中的表达。”Tohoku J Exp Med。

Sato K: "Therapy for renal cell carcinoma oriented to angiogenesis."Proceeding of 5th Otsuka Urologic Oncology Seminar. 5. 7 (2000)

佐藤 K：“以血管生成为导向的肾细胞癌治疗”。第五届大冢泌尿肿瘤学研讨会论文集。

Sato K et al.: "Increased serum levels of vascular endothelial growth factor in patients with renal cell carcinoma."Jpn J Cancer Res. 90. 874-879 (1999)

Sato K 等人：“肾细胞癌患者血管内皮生长因子的血清水平升高。”Jpn J Cancer Res。