NOVEL STRATEGIES FOR OVARIAN CANCER PREVENTION

预防卵巢癌的新策略

• 批准号: 8173260
• 负责人: Jay W Wright
• 金额: $ 4.76万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8173260
• 关键词: Affect; Cancer Patient; Cells; Computer Retrieval of Information on Scientific Projects Database; Data; Detergents; Development; Diagnosis; Disease; Down-Regulation; Early Diagnosis; Elements; Epithelium; Funding; Genes; Grant; Histone Acetylation; Indium; Institution; Malignant neoplasm of ovary; Messenger RNA; Methylation; Molecular Analysis; Ovarian; Ovary; Prevention strategy; Research; Research Personnel; Resources; Risk; Source; Staging; Surface; Survival Rate; System; Therapeutic; Translating; United States National Institutes of Health; Woman; base; clinical application; improved; 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. 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. Current data indicate the OSE may be effectively removed without impairing ovarian function. In addition, we have eliminated FANCD2 gene methylation and histone acetylation as probable mechanisms for its downregulation in at-risk women. Ongoing research will determine whether miRNA's are affecting FANCD2 mRNA levels.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 卵巢表面上皮（OSE）是大多数女性卵巢癌的来源，但占卵巢的不到1/1，000。人们对OSE转化的基础知之甚少，阻碍了改进治疗策略的发展。 由于卵巢癌的预后显着下降时，疾病在后期诊断（95%的治愈率在第一阶段，但只有10%的5年生存率在第四阶段），预防和早期发现的策略可能提供最好的希望，减少卵巢癌的死亡人数。我们正在开发两种预防卵巢癌的新策略：首先，我们寻求完全消除OSE，使用去污剂和轻度磨损（上皮切除术）;其次，我们希望调节OSE中的FANCD 2表达。 该项目更广泛地寻求建立一个研究计划，通过对来自健康、高危和癌症患者的OSE细胞进行微阵列和分子分析，将确定OSE转化的关键因素。非人灵长类系统将用于评估这些元素作为治疗操作的候选者，数据将转化为卵巢癌预防和早期检测治疗的临床应用。目前的数据表明，OSE可以有效地去除而不损害卵巢功能。 此外，我们已经排除了FANCD2基因甲基化和组蛋白乙酰化作为其在高危女性中下调的可能机制。 正在进行的研究将确定miRNA是否影响FANCD2 mRNA水平。