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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 卵巢表面上皮（OSE）是女性中大多数卵巢癌的来源，但不到卵巢的1/1,000。 OSE转化的基础知之甚少，阻碍了改进的治疗策略的发展。 由于卵巢癌的预后在后期诊断出疾病时（在I期的95％治愈率，但第四阶段的5年生存率仅为10％）时，预防和早期检测策略可能会提供减少卵巢癌死亡人数的最佳希望。我们正在开发预防卵巢癌的两种新型策略：首先，我们寻求使用洗涤剂和轻度磨损（上皮切除术）完全消除OSE；其次，我们希望使用组蛋白脱乙酰基酶抑制剂伏地在OSE中调节FANCD2的表达。 FANCD2介导DNA修复，并减少来自具有卵巢癌家族史的女性的培养细胞。 此外，这些细胞还表现出降低的组蛋白3乙酰化，这可能会降低fancd2的表达。 我们将确定Vorinostat在体内是否会提高组蛋白3乙酰化和fancd2的表达。 该项目更广泛地试图建立一个研究计划，从而对健康，处于危险和癌症患者的OSE细胞进行微阵列和分子分析将确定OSE转化中的关键因素。非人类灵长类动物系统将用于评估这些元素作为治疗操作的候选者，并且数据将转化为卵巢癌预防和早期检测疗法的临床应用。