MARKERS OF PROSTATE CANCER PROGRESSION: A TELOMERE-BASED PROTEOMIC APPROACH

前列腺癌进展的标志物：基于端粒的蛋白质组学方法

• 批准号: 8167573
• 负责人: MARCO BISOFFI
• 金额: $ 10.85万
• 依托单位: NEW MEXICO STATE UNIVERSITY LAS CRUCES
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8167573
• 关键词: Biological Markers; Cell model; Clinical; Collection; Computer Retrieval of Information on Scientific Projects Database; Diagnostic; Diagnostic or Prognostic Factor; Disease; Drug Compounding; Epithelial; Frequencies; Funding; Goals; Grant; Human; Institution; Lead; Malignant - descriptor; Malignant neoplasm of prostate; Molecular Profiling; Nature; Patients; Preventive; Progressive Disease; Prostatic Tissue; Proteins; Proteomics; Research; Research Personnel; Resources; Source; Stromal Cells; Testing; Therapeutic Intervention; United States National Institutes of Health; base; experience; high throughput screening; inhibitor/antagonist; novel; prognostic; programs; small molecule; telomere; therapeutic target; tumor; tumor progression

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 long-term goal of our research program is to identify novel biomarkers of prostate cancer and to test their clinical utility either as diagnostic/prognostic factors, or as targets for therapeutic intervention. We thereby focus on the identification of biomarkers for both early as well as progressive disease. We have chosen an integrative approach employing human prostatic tissues of pre- and early malignant nature, as well as more defined cell models of prostate cancer progression. We will focus primarily on markers that can be detected in clinical laboratoried (for example proteins). We propose three progressive Specific Aims: First we will identify biomarkers in (i) epithelial and stromal cells derived from genetically modified tumor adjacent human prostatic tissues by generating proteomic expression profiles in comparison to disease-free prostatic tissues; and (ii) in an established cell model of prostate cancer progression. Second, using our collection of human prostatic tissues, we will validate potential biomarkers in tumor, matched tumor adjacent, and disease-free prostatic tissues. This analysis will allow us to determine the frequency, as well as cellular distribution of these biomarkers. The association of these parameters with clinical patient information will evaluate the marker's diagnostic/prognostic utility. Third, we will subject newly identified potential therapeutic targets to high throughput screening of small molecule inhibitors for the identification of lead drug compounds. These may lead to novel treatments in the preventive and/or adjunctive settting. This integrated approach is driven by an experienced team of biomedical researchers and an established network of trans-disciplinary collaborators.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 我们研究计划的长期目标是确定前列腺癌的新型生物标志物，并测试它们作为诊断/预后因素或作为治疗干预目标的临床效用。因此，我们专注于识别早期和进展性疾病的生物标志物。我们选择了一种综合方法，采用恶性前和早期的人类前列腺组织，以及前列腺癌进展的更明确的细胞模型。我们将主要关注可在临床实验室检测到的标记物（例如蛋白质）。我们提出三个渐进的具体目标： 首先，我们将通过与无病前列腺组织相比生成蛋白质组表达谱来鉴定（i）来自邻近人类前列腺组织的转基因肿瘤的上皮细胞和基质细胞中的生物标志物； (ii) 在已建立的前列腺癌进展细胞模型中。 其次，利用我们收集的人类前列腺组织，我们将验证肿瘤、匹配的肿瘤邻近组织和无病前列腺组织中的潜在生物标志物。该分析将使我们能够确定这些生物标志物的频率以及细胞分布。这些参数与临床患者信息的关联将评估标记物的诊断/预后效用。 第三，我们将对新发现的潜在治疗靶点进行小分子抑制剂的高通量筛选，以鉴定先导药物化合物。这些可能会导致预防性和/或辅助性治疗中的新疗法。 这种综合方法是由经验丰富的生物医学研究人员团队和已建立的跨学科合作者网络推动的。