Development of An In vivo Metastasis Screen

体内转移筛查的开发

• 批准号: 7474745
• 负责人: JEFFREY E SEGALL
• 金额: $ 16.6万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-23 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7474745
• 关键词: Affect; Animals; Automobile Driving; Blood; Cells; Characteristics; Clinical; Complement; Detection; Development; Drug Delivery Systems; Enhancers; Gene Expression; Generations; Genes; Goals; Growth; In Vitro; Individual; Lung; Malignant - descriptor; Malignant Neoplasms; Measures; Metastatic to; Methodology; Methods; Neoplasm Metastasis; Numbers; Open Reading Frames; Patients; Pattern; Primary Neoplasm; Production; Property; Proteins; Purpose; Rate; Regulator Genes; Resources; Screening procedure; Technology; Testing; Validation; cancer cell; drug development; gene function; in vivo; in vivo Model; inhibitor/antagonist; malignant breast neoplasm; neoplastic cell; novel therapeutics; outcome forecast; prognostic; programs; protein expression; size; small hairpin RNA; tool; tumor growth

DESCRIPTION (provided by applicant): The tools and resources are now available for the development of screens for genes that enhance metastasis in vivo. Such screens will identify new targets for drug development that may complement therapies currently under development or in clinical use. In addition, the information provided by such screens will aid in reducing the number of potential targets that are identified through microarray studies by indicating which gene products are likely to be driving metastasis. We propose to combine high throughput gene expression and suppression technologies with in vivo metastasis methodology to accelerate in vivo screening by a factor of up to 50. The screen will indicate the contributions of proteins to the steps of primary tumor growth, intravasation, and lung colonization. The first aim will focus on production of pools of cells expressing or suppressing selected proteins. The second aim will evaluate detection technologies for measuring construct distributions in a pool. The third aim will determine the appropriate formation of pools to be screened. The fourth and fifth aims will perform an initial screen and validate candidates identified in the screen. This R21 application will enable the development of the screen and demonstrate feasibility; providing a paradigm for evaluating gene function for the most critical feature of tumor cell malignancy - the ability to metastasize. ASSESSMENT:

描述（由申请人提供）：现在可使用工具和资源来开发增强体内转移的基因的筛选。此类筛选将确定药物开发的新靶点，这些靶点可能会补充目前正在开发或临床使用的疗法。此外，此类筛选提供的信息将有助于减少通过微阵列研究识别出哪些基因产物可能驱动转移的潜在靶标的数量。我们建议将高通量基因表达和抑制技术与体内转移方法相结合，以将体内筛选加速高达 50 倍。筛选将表明蛋白质对原发性肿瘤生长、内渗和肺部定植步骤的贡献。第一个目标将集中于生产表达或抑制选定蛋白质的细胞库。第二个目标将评估用于测量池中构建体分布的检测技术。第三个目标将确定要筛选的池的适当形成。第四和第五个目标将执行初始筛选并验证筛选中确定的候选人。该R21应用程序将支持屏幕的开发并展示可行性；为评估肿瘤细胞恶性肿瘤最关键特征——转移能力的基因功能提供了一个范例。 评估：