SPORE in Brain Cancer

这项杜克大学脑瘤孢子基金由四个项目组成，五个核心，一个发展研究 计划和职业发展计划。这项拟议研究的目标是增进对 脑肿瘤生物学和病因学，并将其转化为临床方案，代表显著和 这些难以治疗的肿瘤的治疗的新进展。赠款，作为一个整体，以及 每个项目和核心都由基础和临床首席研究员领导。在项目1中，新疗法 靶向GSTP1蛋白的基因在恶性胶质瘤中过度表达，是预后较差的指标 合理开发和评估临床疗效。项目2将研究新的分子 中枢神经系统肿瘤对临床活性脑肿瘤药物泰莫达的耐药机制及评价 PARP抑制剂逆转泰莫达耐药的临床疗效。项目3将调查树突状 以细胞为基础的巨细胞病毒疫苗作为恶性胶质瘤的治疗方式及其基础 抗肿瘤反应的机制。在项目4中，分子和流行病学研究将检查 一项病例对照研究中的脑肿瘤病因学。暴露于可能的神经致癌物质将被检查并 新陈代谢和DNA修复基因的多态将被检测为脑肿瘤风险的决定因素 和治疗相关的毒性。这些核心包括组织采购和遗传学核心，以及 研究新药许可核心、I/II期临床试验核心、生物统计和信息 系统核心，以及将提供关键基础设施和服务职能的行政核心。 发展研究计划将由从整个癌症中心确定的试点项目组成 杜克大学的会员以及来自选定的外部机构的会员。重点是那些没有 之前在神经肿瘤学工作。杜克大学高级调查人员提供的9个试点项目例子 以前没有研究过脑瘤的人都包括在内。有三个潜在职业的例子 I发展奖获得者。他们是Hal Yan博士、Simon Gregory博士和Duane Mitchell博士，非洲人- 美国少数民族。在每个项目和核心描述之前，都要对前面的批评作出回应。

This Duke Brain Tumor SPORE grant consists of four projects, five cores, a Developmental Research Program, and a Career Development Program. The goal of the proposed research is to advance knowledge of brain tumor biology and etiology and to translate these into clinical protocols that represent significant and novel advances in the management of these therapeutically intractable tumors. The grant, as a whole, and each project and core, are led by basic and clinical Principal Investigators. In Project 1, novel therapeutics that target the GSTP1 protein, overexpressed and a poor prognostic indicator in malignant gliomas, will be rationally developed and evaluated for clinical efficacy. Project 2 will investigate novel molecular mechanisms of resistance of CNS tumors to Temodar, a clinically active brain tumor agent and evaluate the clinical efficacy of a PARP inhibitor in reversing Temodar resistance. Project 3 will investigate dendritic cell-based vaccination against CMV as a therapeutic modality in malignant glioma and the underlying mechanisms of the anti-tumor response. In Project 4, molecular and epidemiologic studies will examine the etiology of brain tumors in a case-control study. Exposure to putative neurocarcinogens will be examined and polymorphisms in metabolism and DNA repair genes will be examined as a determinant of brain tumor risk and treatment-associated toxicity. The cores include a Tissue Procurement and Genetics Core, an Investigational New Drug Permit Core, a Phase I/II Clinical Trials Core, a Biostatistics and Information Systems Core, and an Administrative Core which will provide critical infrastructural and service functions. The Developmental Research Program will consist of pilot projects identified from the entire Cancer Center membership at Duke as well as from selected, outside institutions. Emphasis is on investigators who have not previously worked in neuro-oncology. Nine examples of pilot projects from senior investigators at Duke who have not previously worked on brain tumors are included. There are three examples of potential Career IDevelopment awardees. They are Dr. Hal Yan, Dr. Simon Gregory, and Dr. Duane Mitchell, an African- American minority. A response to the previous critique precedes each project and core description.