NOVEL STRATEGIES FOR OVARIAN CANCER PREVENTION

预防卵巢癌的新策略

• 批准号: 7958533
• 负责人: Jay W Wright
• 金额: $ 3.45万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-04 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7958533
• 关键词: Acetylation; Cancer Patient; Cells; Computer Retrieval of Information on Scientific Projects Database; DNA Repair; Data; Detergents; Development; Diagnosis; Disease; Early Diagnosis; Elements; Epithelium; Exhibits; Family history of; Funding; Grant; Histone Deacetylase Inhibitor; Histones; Indium; Institution; Malignant neoplasm of ovary; Mediating; Molecular Analysis; Ovarian; Ovary; Prevention strategy; Primates; Research; Research Personnel; Resources; Risk; Source; Staging; Surface; Survival Rate; System; Therapeutic; Translating; United States National Institutes of Health; Vorinostat; Woman; base; clinical application; improved; in vivo; nonhuman primate; novel strategies; outcome forecast; ovarian cancer prevention; programs; treatment strategy

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The ovarian surface epithelium (OSE) is the source of most ovarian cancers in women, yet comprises less than 1/1,000th of the ovary. The basis for OSE transformation is poorly understood, hindering the development of improved strategies for treatment. Since the prognosis for ovarian cancer declines dramatically when the disease is diagnosed at later stages (95% cure rate at stage I, but a 5-year survival rate of only 10% at stage IV), strategies for prevention and early detection may offer the best hope of reducing the number of fatalities from ovarian cancer. We are developing two novel strategies for ovarian cancer prevention: first, we seek to eliminate the OSE completely, using detergent and mild abrasion (epitheliectomy); second, we wish to modulate FANCD2 expression in the OSE using the histone deacetylase inhibitor Vorinostat. FANCD2 mediates DNA repair, and is reduced in cultured OSE cells derived from women with a family history of ovarian cancer. In addition, these cells also exhibit decreased Histone 3 acetylation, which may reduce FANCD2 expression. We will determine whether Vorinostat elevates Histone 3 acetylation and FANCD2 expression in vivo. This project more broadly seeks to establish a research program whereby microarray and molecular analysis of OSE cells from healthy, at risk, and cancer patients will identify key elements in OSE transformation. The nonhuman primate system will be used to evaluate these elements as candidates for therapeutic manipulation, and the data will be translated into clinical application for ovarian cancer prevention and early detection therapies.

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