Development of Antibodies to Angiogenic Factors for Diagnosis and Therapy of Solid Tumors.

用于实体瘤诊断和治疗的血管生成因子抗体的开发。

• 批准号: 09557129
• 负责人: KATO Tetsuro
• 金额: $ 7.87万
• 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: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09557129/
• 关键词: angiogenic factor; urogenital cancer; VEGF; bFGF; ELISA; angiogenesis; 腎細胞癌; 血中VEGF; 生化学的指標; 血管増殖因子; 抗癌剤; 癌診断

The relationship between tumor angiogenesis and angiogenic factors was evaluated in renal cell carcinoma (RCC) and urinary bladder carcinoma (BCィイD2aィエD2). VEGF genes, VEGFィイD2121ィエD2 and VEGFィイD2165ィエD2, were overexpressed in 60% of RCCs. The Expression level of VEGF genes was significantly correlated with the intratumoral microvessel density. An immunohistologic analysis was done with and anti-VEGF antiserum that had been raised by immunizing a rabbit with an oligopeptide homologous to the N-terminal of VEGF. Cytoplasm of RCC appeared to be positive to the VEGF staining. VEGF genes were 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 Bca is suggested to be facilitated by a paracrine mechanism with VEGF and its receptors.VEGF-relating genes (VEGF-A,B,C, and D) and their receptor genes have been … More cloned one after another. We studies the expression of these genes 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 a RCC patient group and a healthy control group. 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. When the VEGF cut-off value was set at 100pg/ml based on a receiver-operator curve analysis, the sensitivity and the specificity of RCC were 80.0% and 72.5%, respectively. Thus we suggest that RCC releases VEGF into the blood circulation and serum VEGF level would be a marker of malignant potential of RCC.Taken together, these results would be useful as basic data for the development of anti-angiogenic-factor antibody facilitating diagnosis and therapy of RCC. Less

本研究探讨了肾细胞癌（RCC）和膀胱癌（BC细胞癌D2 a和BC细胞癌D2）中肿瘤血管生成与血管生成因子的关系。60%的RCC中VEGF基因，VEGF受体D2121亚型D2和VEGF受体D2165亚型D2过表达。VEGF基因表达水平与肿瘤微血管密度显著相关。用与VEGF的N-末端同源的寡肽免疫兔而产生的抗VEGF抗血清进行免疫组织学分析。肾细胞癌细胞质中VEGF染色呈阳性。VEGF基因在40%的Bcas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。VEGF相关基因（VEGF-A、B、C和D）及其受体基因已被证实是一种与VEGF及其受体相关的基因。 ...更多信息 一个接一个的克隆。我们研究了这些基因在肾细胞癌中的表达，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。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。根据受试者-操作者曲线分析，当VEGF临界值设为100 pg/ml时，肾癌的敏感性和特异性分别为80.0%和72.5%。提示肾细胞癌可释放VEGF，血清VEGF水平可作为肾细胞癌恶性潜能的一个标志，为研制抗血管生成因子抗体提供了基础资料，有助于肾细胞癌的诊断和治疗。少

项目成果

佐藤一成、 加藤哲郎: "腎細胞癌における腫瘍血管の増生と血管増生因子の相関" 癌と化学療法. 24. 389-39 (1997)

Kazunari Sato、Tetsuro Kato：“肾细胞癌中肿瘤血管增殖与血管生长因子的相关性”《癌症与化疗》24. 389-39 (1997)。

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

Kazunari Sato 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。

Sato K et al.: "Increased serum levels of vascular endothelial growth factor in patients with renal cell carcinoma."Jpn J Cancer Res. 90. 874-9 (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。

Norihiko Tsuchiya, et al.: "Quantitative analysis of VEGF,VEGF-C and VEGFR-2 gene expression in renal cell carcinoma"J Urol. 161. 143A (1999)

Norihiko Tsuchiya 等：“肾细胞癌中 VEGF、VEGF-C 和 VEGFR-2 基因表达的定量分析”J Urol。

佐藤一成、加藤哲郎: "腎細胞癌における腫瘍血管の増生と血管増生因子の相関"癌と化学療法. 24. 389-394 (1997)

Kazunari Sato、Tetsuro Kato：“肾细胞癌中肿瘤血管增殖与血管生长因子的相关性”《癌症与化疗》24. 389-394 (1997)。