ANGIOGENESIS IN OVARIAN EPITHELIAL CARCINOMA

卵巢上皮癌中的血管生成

• 批准号: 6336420
• 负责人: ROBERT B JAFFE
• 金额: $ 23.06万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-30 至 2001-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6336420
• 关键词: angiogenesis; angiogenesis factor; athymic mouse; carcinoma; estradiol; female; fluorescent in situ hybridization; gene expression; growth factor receptors; growth inhibitors; human genetic material tag; human tissue; in situ hybridization; metastasis; neoplasm /cancer blood supply; neoplasm /cancer immunotherapy; neoplastic growth; neoplastic process; neutralizing antibody; nonhuman therapy evaluation; northern blottings; ovary neoplasms; passive immunization; receptor expression; vascular endothelium

The development of a vascular supply is an essential component of tumor growth. Our preliminary studies in immunodeficient mice indicate that vascular endothelial growth factor (VEGF) mediates tumor-directed angiogenesis in ovarian epithelial carcinoma, at least during early stages of tumor growth. Inhibition of VEGF action with a neutralizing antibody to VEGF inhibited the neovascularization and growth of SKOV3-derived tumors in the subcutaneous and intraperitoneal tissue of immunodeficient mice. With cessation of treatment, tumor, neovascularization and growth resumed. Our underlying hypothesis is that angiogenesis is necessary to promote the growth and spread of primary human ovarian epithelial carcinomas. To test this hypothesis, neovascularization and growth of subcutaneous and intraperitoneal tumors derived from SKOV3, OVCAR-3 and primary human ovarian cancer cells will be examined following treatment with a neutralizing antibody to VEGF. We will asses whether inhibition of tumor- directed angiogenesis by passive immunization against tumor-derived VEGF inhibits the growth of both initial and advanced tumors and prolongs survival in these animals. The effect of other anti-angiogenic agents (e.g., 2-methoxyestradiol, thrombospondin, 16kDa fragment of prolactin) on tumor neovascularization and growth also will be examined. Furthermore, we will characterize VEGF and VEGF receptor expression in ovarian cancer and assess whether expression of VEGF and/or its receptors correlates with cancer stage and degree of vascularization, and whether VEGF is an independent negative prognostic indicator of patient survival. This proposal is designed to elucidate the role of angiogenesis in the basic biology of ovarian epithelial carcinoma. We will assess the usefulness of VEGF expression and tumor vascularization as prognostic indicators of patient outcome and examine the anti-tumor effects of inhibiting angiogenesis in biologically relevant models of this malignancy. Elucidating the growth factors involved in, and blocking the angiogenic process necessary for, ovarian cancer neovascularization represents a novel method for inhibiting the growth of this malignancy, potentially leading to advances in prognosis, treatment and survival.

血管供应的发展是肿瘤的重要组成部分 增长 我们对免疫缺陷小鼠的初步研究表明， 血管内皮生长因子（VEGF）介导肿瘤定向 卵巢上皮癌的血管生成，至少在早期阶段 肿瘤的生长。 用抗VEGF中和抗体抑制VEGF作用 VEGF抑制SKOV 3来源肿瘤的新生血管和生长， 免疫缺陷小鼠的皮下和腹膜内组织。 与 停止治疗，肿瘤、新血管形成和生长恢复。 我们 潜在的假设是，血管生成是必要的，以促进 原发性人卵巢上皮癌的生长和扩散。 测试 这一假设，新血管形成和生长的皮下和 来源于SKOV 3、OVCAR-3和原代人的腹膜内肿瘤 卵巢癌细胞将在治疗后进行检查， 抗VEGF中和抗体。 我们将评估是否抑制肿瘤- 通过针对肿瘤源性VEGF的被动免疫的定向血管生成 抑制初始和晚期肿瘤的生长， 这些动物的生存。 其他抗血管生成剂的作用 (e.g., 2-甲氧基乙烯，血小板反应蛋白，催乳素的16 kDa片段）对 还将检查肿瘤新血管形成和生长。 而且我们 将表征卵巢癌中VEGF和VEGF受体的表达， 评估VEGF和/或其受体的表达是否与 癌症阶段和血管化程度，以及VEGF是否是 患者生存率的独立阴性预后指标。 这 该提案旨在阐明血管生成在基础 卵巢上皮癌的生物学 我们将评估 VEGF表达和肿瘤血管化作为预后指标 患者的结果，并检查抑制 在这种恶性肿瘤的生物学相关模型中的血管生成。 阐明参与和阻断血管生成的生长因子 卵巢癌新血管形成所必需的过程代表了一种新的 抑制这种恶性肿瘤生长的方法， 在预后、治疗和生存方面的进展。