Evaluation of biological characteristics in tumor vessels and clinical application of antagonistic agent for neovascularization

肿瘤血管生物学特性评价及新生血管拮抗剂的临床应用

• 批准号: 07457257
• 负责人: KANEMATSU Takashi
• 金额: $ 1.86万
• 依托单位: Nagasaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07457257/
• 关键词: Angiogenesis; PLC; PRF; 5 (Alexander) cells; Ets-1; Hepatocellular carcinoma; Metastatic liver tumor; TNF-alpha; VEGF; bFGF; 内皮細胞; 血管新生阻害剤

BackgroundRecently, it has been reported that a certain carcinogenetic promoter has an angiogenetic activity while retinoid and derivatives from vitamin D3 inhibit carcinogenesis thorough depression of angiogenesis. These reports indicate that angiogenesis may play an important role on carcinogenesis. In clinical settings, angiogenesis is crucial for tumor growth and metastasis. Thus, we investigate the following.Aims1) to examine relationship between angiogenetic factors and proliferative activity for vascular endothelium (EA-HY 926) using colon cancer cells, metastastatic cells of colon cancer to liver, and cells of human hepatocellular carcinoma, and to clarify whether TNT-alpha is able to inhibit angiogenesis or not2) to investigate the angiogenetic activity of PLC/PRF/5 (Alexander) cells, which is a human hepatoma cell line, with diffusion chamber assay using E 26 transformation-specific-1 (Ets-1)Results and Conclusion1) Mean proliferative activity of colon cancer cells and metastasized cells was l42 %, and l52 %, respectively. Although it was not ruled out of the possibility that there were other factors, colon cancer cells produced angiogenetic factors such as VEGF in original cancer cells and bFGF in the metastasized cells. TNF-alpha was not effective on inhibition of angiogenesis.2) Alexander cells accelerate angiogenesis in diffusion chamber assay and Ets- 1 was positive in the endothelium of the new vessels. These results suggest that hepatocellular carcinoma has strong proliferative activity for angiogenesis and Ets- 1 may play an important role on angiogenesis.

研究背景近年来，有研究表明某些致癌促进剂具有促血管生成活性，而维甲酸及其衍生物通过抑制血管生成来抑制肿瘤的发生。这些报道表明血管生成在肿瘤发生中可能起重要作用。在临床环境中，血管生成对于肿瘤生长和转移至关重要。因此，我们进行了以下研究：1）研究血管生成因子与血管内皮细胞增殖活性之间的关系（EA-HY 926）使用结肠癌细胞、结肠癌肝转移细胞和人肝细胞癌细胞，并阐明TNT-α是否能够抑制血管生成2）研究PLC/PRF/5的血管生成活性（亚历山大）细胞的增殖活性。结果与结论1）结肠癌细胞和转移细胞的平均增殖活性分别为142%和152%。虽然不排除存在其他因素的可能性，但结肠癌细胞产生血管生成因子，例如原始癌细胞中的VEGF和转移细胞中的bFGF。2）亚历山大细胞能促进新生血管的形成，Ets- 1在新生血管内皮呈阳性表达。这些结果表明，肝细胞癌具有较强的促血管生成的增殖活性，Ets- 1可能在血管生成中起重要作用。