ANGIOGENESIS IN OVARIAN EPITHELIAL CARCINOMA

血管供应的发展是肿瘤的重要组成部分。 成长。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)介导的肿瘤导向 卵巢上皮癌中的血管生成，至少在早期 肿瘤的生长。抗血管内皮生长因子中和抗体抑制血管内皮生长因子的作用 血管内皮细胞生长因子抑制SKOV3来源肿瘤的新生血管和生长 免疫缺陷小鼠的皮下和腹膜组织。使用 停止治疗，肿瘤、新生血管和生长恢复。我们的 潜在的假说是，血管生成对于促进 原发卵巢上皮癌的生长和扩散。为了测试 这一假说，皮下和皮下组织的新生血管和生长 来源于SKOV3、OVCAR-3和原代人的腹膜肿瘤 卵巢癌细胞将在接受治疗后进行检查 抗血管内皮生长因子中和抗体。我们将评估是否抑制肿瘤- 肿瘤源性血管内皮生长因子被动免疫定向血管生成 抑制初发和晚期肿瘤的生长并延长 在这些动物身上存活。其他抗血管生成药物的作用 (例如，2-甲氧基雌二醇、凝血酶敏感蛋白、催乳素的16 kDa片段) 还将检查肿瘤新生血管和生长情况。此外，我们 将表征卵巢癌和卵巢癌中血管内皮生长因子及其受体的表达 评估血管内皮生长因子及其受体的表达是否与 肿瘤分期和血管形成程度，以及血管内皮生长因子是否是一种 患者生存的独立阴性预后指标。这 建议旨在阐明血管生成在基础血管生成中的作用 卵巢上皮癌生物学。我们将评估以下项目的有用性 血管内皮生长因子表达和肿瘤血管生成作为预后指标的研究 患者预后和检测抑制的抗肿瘤效果 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 卵巢癌新生血管形成所需的过程代表了一种新的 抑制这种恶性肿瘤生长的方法，可能会导致 预后、治疗和生存的研究进展。

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.