BIOLOGY OF OVARIAN CANCER PROGRAM PROJECT

卵巢癌生物学计划项目

• 批准号: 2871834
• 负责人: ROBERT B JAFFE
• 金额: $ 138.36万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-04-15 至 2001-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2871834
• 关键词: female; neoplastic process; ovary neoplasms; vascular endothelial growth factors

The overall goal of the proposed project grant (PPG) is to assemble an interdisciplinary group of talented investigators from different fields to study the biology of ovarian cancer. The general theme of the PPG deals with the growth aspects of ovarian tumor progression. The hypothesis to be addressed is that the onset and progression of ovarian tumors is dependent on aspects of growth regulation (i.e., genetic aberrations, stromal environment, angiogenesis, and local growth facto production) that directly influence tumor categorization, grade and stage. The present application consists of 4 interdisciplinary individual research projects and three core facilities. Project 1. (Michael Skinner) investigates cell-cell interactions and ovarian cancer. The hypothesis tested is that ovarian surface epithelial cells. (OSE) are regulated by mesenchymal (stromal)-epithelial cell interactions mediated by the local production and action of growth stimulators and growth inhibitors. Observations indicate that ovarian tumor growth is dramatically influenced by the stromal environment. The biology of normal and tumorigenic OSE will be examined. Project 2 (Robert Jaffe) investigates angiogenesis in ovarian epithelial carcinoma. The hypothesis tested is that the action of vascular endothelial growth factor (VEGF) is necessary to promote the neovascularization and tumor growth of human ovarian epithelial carcinoma. The extent of angiogenesis and expression of VEGF will also be correlated with tumor progression (i.e., tumor stage and grade). Project 3 (Joe Gray) investigates the role of allelic imbalance in ovarian cancer progression. Using analysis of loss of heterozygosity (LOH), comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH), the chromosomal mapping of common allelic imbalance will be correlated with tumor progression (i.e., tumor stage and grade). Genes will be positionally cloned in regions of common imbalance and, in collaboration with the other projects, genes of interest (e.g., growth factors and receptors) will be mapped and correlated to chromosomal maps. Project 4 (Gordon Mills) investigates a recently purified ovarian cancer ascites factor (OCAF) from ascites fluid of ovarian cancer patients and its role in tumor growth and progression. The hypothesis tested is that OCAF produced by ovarian cancer cells plays a role in tumorigenesis by increasing proliferation of ovarian cancer cells, decreasing sensitivity to chemotherapy, and altering immune responsiveness. These research activities will be supported by the Administrative Core for the coordination and management of the PPG. Thr Molecular Cytometry Core will provide chromosomal mapping (i.e., LOH, CGH and FISH) and technical assistance with FISH of tissue sections. The Tissue/Pathology Core, directed by Bethan Powell, will collect, catalog, and prepare human ovarian cancer surgical specimens and cell-lines for the proposed research. The integrated activities of the four projects and investigators provides a comprehensive examination of the biology of ovarian cancer with emphasis on the growth aspects of tumor progression. Observations are anticipated to provide insight into the future design of more effective therapeutic agents for the prevention, early diagnosis and treatment of ovarian cancer.

拟议项目赠款（PPG）的总体目标是组装 来自不同领域的才华横溢的调查员跨学科小组 研究卵巢癌的生物学。 PPG交易的一般主题 随着卵巢肿瘤进展的生长方面。 假设是 解决的是，卵巢肿瘤的发作和进展取决于 在生长调节方面（即遗传畸变，基质 环境，血管生成和局部增长事实生产） 直接影响肿瘤分类，等级和阶段。 现在 申请由4个跨学科的个人研究项目组成 和三个核心设施。 项目1。（迈克尔·斯金纳）调查 细胞 - 细胞相互作用和卵巢癌。 检验的假设是 卵巢表面上皮细胞。 （OSE）受间充质调节 （基质） - 由局部产生介导的上皮细胞相互作用和 生长刺激剂和生长抑制剂的作用。 观察表明 卵巢肿瘤的生长受到基质的巨大影响 环境。 将检查正常和肿瘤性OSE的生物学。 项目2（罗伯特·贾夫（Robert Jaffe））研究卵巢上皮的血管生成 癌。 测试的假设是血管的作用 内皮生长因子（VEGF）对于促进 人卵巢上皮癌的新血管形成和肿瘤生长。 VEGF的血管生成和表达的程度也将相关 肿瘤进展（即肿瘤期和等级）。 项目3（乔·格雷） 研究等位基因失衡在卵巢癌进展中的作用。 使用杂合性丧失（LOH）的分析，比较基因组 杂交（CGH）和荧光原位杂交（FISH）， 常见等位基因失衡的染色体图将与 肿瘤进展（即肿瘤期和等级）。 基因将是 位置克隆在共同的不平衡区域，并合作 随着其他项目，感兴趣的基因（例如增长因素和 受体）将映射并与染色体图相关。 项目4 （Gordon Mills）研究了最近纯化的卵巢癌腹水 卵巢癌患者腹水液的因素（OCAF）及其在 肿瘤的生长和进展。 检验的假设是OCAF产生 卵巢癌细胞通过增加在肿瘤发生中起作用 卵巢癌细胞的增殖，降低对 化学疗法并改变免疫反应能力。 这些研究 活动将得到行政核心的支持 PPG的协调和管理。 分子细胞仪核心将 提供染色体图（即LOH，CGH和FISH）和技术 帮助组织切片鱼。 组织/病理核心， 由贝森·鲍威尔（Bethan Powell）执导，将收集，编目和准备人类卵巢 癌症手术标本和细胞线，用于拟议的研究。 这 四个项目的综合活动和调查人员提供了 全面检查卵巢癌的生物学，重点 肿瘤进展的生长方面。 预计观察 洞悉更有效的治疗剂的未来设计 为了预防，早期诊断和治疗卵巢癌。