Multiplex Gene Expression in Single Cells for Circulating Tumor Cell Detection

用于循环肿瘤细胞检测的单细胞多重基因表达

• 批准号: 7135419
• 负责人: YULING LUO
• 金额: $ 10万
• 依托单位: ADVANCED CELL DIAGNOSTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-05 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7135419
• 关键词: blood; blood cells; body fluids; bone marrow; gene expression; mammary gland; neoplasm /cancer; neoplasm /cancer diagnosis; neoplastic cell; prostate neoplasms

DESCRIPTION (provided by applicant): The detection and enumeration of circulating tumor cells (CTC) has the potential to become a very powerful tool in cancer diagnosis and treatment. However, current technologies for CTC detection are not yet established in routine clinical practice. 1 primary reason is that CTCs present in body fluids at extremely low concentrations of 1 in 1 million or more normal hetergeneous cells. Existing technologies lack the sensitivity and specificity required for reliable and reproducible detection of these rare CTCs. Another reason is that current technology does not distinguish well the "live" from "dead" or "dying" CTCs. The overall goal of this research proposal is to develop an assay technology named QMAGEX for Quantitative Multiplex Analysis of Gene Expression in Single Cells in Suspension and to utilize the technology for sensitive detection, accurate enumeration, and functional analysis of CTCs in body fluids. The long-term goal of this effort is to leverage this assay technology to develop a suite of high value cancer diagnostic products. These products would satisfy many significant unmet needs in cancer diagnosis, especially in the areas of early detection, therapy guidance, and recurrence monitoring. The research effort described in this Phase I SBIR application represents the first, "proof-of-concept" step towards the long-term goal. Well characterized breast and prostate cancer cell lines will be used as a model system and detection and enumeration of CTC at a clinically useful concentration (1 CTC in every 10,000 normal white blood cells) will be demonstrated. If successful, Phase II effort will be aimed at developing high information content QMAGEX assay for detection of CTC at a concentration below 1 in 1 to 10 million normal white blood cells. The assay will be tested in real clinical blood or bone marrow samples and their clinical utility evaluated. Commercial diagnostic products focusing on specific cancers and specific diagnostic applications will be developed in Phase III.

描述（由申请人提供）：循环肿瘤细胞（CTC）的检测和计数有可能成为癌症诊断和治疗中非常强大的工具。然而，目前的CTC检测技术尚未在常规临床实践中建立。一个主要原因是CTC以极低的浓度存在于体液中，为1/100万或更多的正常异质细胞。现有技术缺乏可靠和可重复检测这些罕见CTC所需的灵敏度和特异性。另一个原因是，目前的技术不能很好地区分“活的”CTC与“死的”或“垂死的”CTC。本研究计划的总体目标是开发一种名为QMAGEX的检测技术，用于悬浮单细胞中基因表达的定量多重分析，并利用该技术对体液中的CTC进行灵敏检测、准确计数和功能分析。这项工作的长期目标是利用这种检测技术开发一套高价值的癌症诊断产品。这些产品将满足癌症诊断中许多尚未满足的重要需求，特别是在早期检测、治疗指导和复发监测领域。在第一阶段SBIR应用中描述的研究工作代表了实现长期目标的第一个“概念验证”步骤。 充分表征的乳腺癌和前列腺癌细胞系将用作模型系统，并将证明在临床有用浓度（每10，000个正常白色血细胞中1个CTC）下CTC的检测和计数。如果成功，第二阶段的努力将旨在开发高信息含量的QMAGEX测定，用于检测浓度低于1/1至1000万正常白色血细胞中的CTC。将在真实的临床血液或骨髓样本中检测该检测试剂盒，并评价其临床效用。第三阶段将开发针对特定癌症和特定诊断应用的商业诊断产品。

项目成果

Viable circulating tumour cell detection using multiplex RNA in situ hybridisation predicts progression-free survival in metastatic breast cancer patients.

• DOI: 10.1038/bjc.2012.137
• 发表时间: 2012-05-22
• 期刊: BRITISH JOURNAL OF CANCER
• 影响因子: 8.8
• 作者: Payne, R. E.;Wang, F.;Su, N.;Krell, J.;Zebrowski, A.;Yaguee, E.;Ma, X-J;Luo, Y.;Coombes, R. C.
• 通讯作者: Coombes, R. C.

RNAscope for in situ detection of transcriptionally active human papillomavirus in head and neck squamous cell carcinoma.

• DOI: 10.3791/51426
• 发表时间: 2014-03-11
• 期刊: Journal of visualized experiments : JoVE
• 作者: Wang H;Wang MX;Su N;Wang LC;Wu X;Bui S;Nielsen A;Vo HT;Nguyen N;Luo Y;Ma XJ
• 通讯作者: Ma XJ