BIOLOGY OF HIGH RISK GERM CELL NEOPLASIA

高风险生殖细胞肿瘤的生物学

• 批准号: 2887994
• 负责人: LAWRENCE H EINHORN
• 金额: $ 85.45万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-06 至 2002-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2887994
• 关键词: cancer risk; germ cell neoplasms

OVERALL DESCRIPTION (Applicant's Description): Germ cell tumors (GCT), while uncommon, are still the leading cause of cancer in young adult males. Studies performed here at Indiana University have lead to therapeutic advances that now cure approximately eight out of ten patients with disseminated germ cell tumors. However, the remaining 20 percent have been intractable to therapy. Yet it is difficult to distinguish curable from incurable GCT at presentation with current clinically-based prognostic models. This question is probably the most important remaining issue in germ cell neoplasia. The central hypothesis driving this program is that there are molecular and cellular characteristics of high versus normal risk GCT. Defining these characteristics will certainly have diagnostic benefit, in that these patients could have aggressive therapy such as stem cell transplant offered prior to overwhelming disease or organ failure. In addition, it is possible that this group could have treatment studies defined for them, allowing the majority of germ cell patients to escape the increased toxicity that an aggressive regimen or surgery might bring. This program will attempt to define the molecular and cellular characteristics of high risk GCT in three projects. Project 1 will study the role that the novel transcriptional repressor Genesis has in GCT. Project 2 will isolate and characterize amplified GCT oncogenes on the marker chromosome iso12p. Project 3 will use PCR to analyze the significance of minimal residual circulating GCT cells. Core A will regulate sample distribution. Core B will collect the clinical data obtained from its own efforts, and scientific data from the other projects, and correlate it with clinical presentation and outcome of GCT. Core C will serve as the administrative center. The ultimate goal of this program is to define a prognostic model based on molecular and cellular characteristics that can distinguish high risk GCT. These distinguishing characteristics are potential targets for future therapy.

总体描述（申请人的描述）：生殖细胞肿瘤（GCT）虽然罕见，但仍然是年轻成年男性癌症的主要原因。 印第安纳大学在这里进行的研究导致了治疗进展，目前可以治愈十分之八的分布生殖细胞肿瘤的患者。 但是，其余的20％对治疗很棘手。 然而，很难通过目前基于临床的预后模型将可治疗的GCT与无法治愈的GCT区分开。 这个问题可能是生殖细胞肿瘤中最重要的问题。 推动该程序的中心假设是，高风险与正常风险的分子和细胞特征。 定义这些特征肯定会具有诊断益处，因为这些患者可以在压倒性疾病或器官衰竭之前提供诸如干细胞移植等侵略性疗法。 此外，这一组可能会为他们定义治疗研究，从而使大多数生殖细胞患者能够避免侵略性方案或手术可能带来的毒性增加。 该计划将尝试在三个项目中定义高风险GCT的分子和细胞特征。 项目1将研究新型的转录阻遏物在GCT中的作用。 项目2将隔离并表征标记染色体ISO12p上的扩增的GCT癌基因。项目3将使用PCR分析最小残留循环GCT细胞的重要性。 核心A将调节样本分布。 核心B将收集从自己的努力中获得的临床数据，以及来自其他项目的科学数据，并将其与GCT的临床表现和结果相关联。 C核心将作为行政中心。 该程序的最终目标是定义基于可以区分高风险GCT的分子和细胞特征的预后模型。这些明显的特征是未来治疗的潜在目标。