BIOLOGY OF OVARIAN CANCER PROGRAM PROJECT

卵巢癌生物学计划项目

• 批准号: 6334815
• 负责人: ROBERT B JAFFE
• 金额: $ 49.08万
• 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/6334815
• 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.

拟议项目赠款的总体目标是， 来自不同领域的跨学科研究人员， 研究卵巢癌的生物学。 PPG交易的一般主题 与卵巢肿瘤的生长有关 假设是 卵巢肿瘤的发生和发展依赖于 关于生长调节的方面（即，遗传畸变，基质 环境、血管生成和局部生长因子 生产）， 直接影响肿瘤的分类、分级和分期。 本 申请包括4个跨学科的个人研究项目 三大核心设施。 项目1。 （迈克尔斯金纳）调查 细胞间相互作用和卵巢癌。 检验的假设是， 卵巢表面上皮细胞 (OSE)是由间充质 （基质）-上皮细胞相互作用介导的本地生产和 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间质细胞的显著影响 环境 将检查正常和致瘤性OSE的生物学。 项目2（Robert Jaffe）研究卵巢上皮血管生成 carcinoma. 所检验的假设是， 内皮生长因子（VEGF）是促进 人卵巢上皮癌的新生血管形成和肿瘤生长。 血管生成的程度和VEGF的表达也将相关 随着肿瘤进展（即，肿瘤分期和分级）。 项目3（乔·格雷） 研究等位基因失衡在卵巢癌进展中的作用。 利用杂合性缺失（洛）分析、比较基因组学方法， 杂交（CGH）和荧光原位杂交（FISH）， 常见等位基因不平衡的染色体作图将与 肿瘤进展（即，肿瘤分期和分级）。 基因会 在共同不平衡的区域进行位置克隆， 对于其他项目，感兴趣的基因（例如，生长因子和 受体）将被绘制并与染色体图谱相关联。 项目4 （戈登米尔斯）调查最近纯化的卵巢癌腹水 卵巢癌患者腹水中OCAF的表达及其在卵巢癌治疗中的作用 肿瘤生长和进展。 测试的假设是，OCAF产生 卵巢癌细胞在肿瘤发生中起作用， 卵巢癌细胞的增殖，降低对 化疗和改变免疫反应。 这些研究 活动将得到行政核心的支持， PPG的协调和管理。 分子细胞计数核心将 提供染色体作图（即，洛缺失、CGH和FISH）和技术 协助组织切片的FISH。 组织/病理学核心， 由Bethan Powell指导，将收集，分类，并准备人类卵巢 癌症手术标本和细胞系用于拟议的研究。 的 四个项目和调查人员的综合活动提供了一个 卵巢癌的生物学的全面检查，重点是 肿瘤进展的生长方面。 预计观察结果将 为未来设计更有效的治疗药物提供了见解 用于卵巢癌的预防、早期诊断和治疗。