Detection of Carcinomas

癌症检测

• 批准号: 8042478
• 负责人: Xiaojing Zhang
• 金额: $ 32.4万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8042478
• 关键词: Appearance; Automation; Biological Assay; Biopsy; Blood; Blood Circulation; Blood Tests; Breast; Breast Cancer Cell; Breast Carcinoma; Carcinoma; Cells; Clinical Pathology; Detection; Development; Devices; Diagnosis; Early Diagnosis; Ensure; Evaluation; FDA approved; Goals; Growth; Hour; Image; Laboratories; Magnetism; Malignant - descriptor; Malignant Neoplasms; Measures; Methods; Microfluidics; Microscope; Microscopic; Microscopy; Mutation; Neoplasm Metastasis; Non-Malignant; Organ; Pathologist; Patients; Pattern; Physicians; Research; Screening procedure; Sensitivity and Specificity; Solid Neoplasm; Staging; Technology; Time; Tissues; Treatment Effectiveness; Tumor Markers; anticancer research; base; cancer cell; cancer diagnosis; disease diagnosis; improved; innovation; instrument; instrumentation; malignant breast neoplasm; microchip; nanomagnetic; nanoparticle; nanoscale; neoplastic cell; novel; outcome forecast; particle; programs; prototype; tumor

DESCRIPTION (provided by applicant): The long term objective of this research is to diagnose cancer via a blood test at an earlier stage and thereby increase the cure rate. We will focus in this program on developing our two instruments to follow genetic changes associated with progressive carcinoma and thereby, eventually help to personalize therapy. It is known that malignant solid tumors shed tumor cells into the circulation at a relatively early stage in their growth. Therefore, if it were possible to capture these relatively rare cells (CTCs) and prove that they are malignant, earlier diagnosis would be expected. Microchips that capture CTCs with great sensitivity have been recently described. We have made such a microchip with proven sensitivity but have altered it using immunolablled nanomagnetic particles for capturing CTCs, which can then be released to an innovative hyperspectral imaging microscope (HMI) that can precisely quantify 10 tumor markers (TMs) in a single pass. The proposed CTC chip-HMI platform can find tumor markers in blood in less than an hour, and with 10-fold greater sensitivity and specificity then existing (commercial) devices such as Cell Tracks, an FDA approved instrument for determining prognosis and treatment effectiveness in breast cancer based on a very small number of captured CTCs. A major breakthrough is the demonstration that over expression of TMs by cancer breast cells allows them to be distinguished from normal breast cells which have consistently less over expression of TMs. Therefore, after capture of the CTCs, evaluation of their TM expression by the HMI and the pathologist's conclusion concerning malignancy, we can then allow for the development of criteria for the number and extent of TM over expression that minimizes false positives but not at the expense of increasing false negatives. The extent and patterns of over expression of particular TMs will also be of considerable value for prognosis and treatment decisions. We will study breast carcinoma as a prototype of other carcinomas, primarily due to that the malignant tumors can be precisely measured radiographically and we have a large supply of patients. We plan to focus on the ability of our instrumentation to find CTCs in patients with small breast carcinomas. PUBLIC HEALTH RELEVANCE: A major goal in cancer research is to diagnose the disease earlier. There is substantial evidence that early diagnosis of cancer can improve the cure rate significantly. We are developing devices at a nanoscale level that will be very effective at capturing the circulating tumor cells and presenting them to a novel microscope. The new microscope will analyze these suspicious cells and determine whether or not they are cancer cells by their content of over expressed tumor markers. In addition to early diagnosis, expression of these tumor markers will help the physician to prognosticate and determine which treatments should be administered to the patient.

描述（由申请人提供）：这项研究的长期目的是通过早期的血液检查诊断癌症，从而提高治愈率。我们将专注于该计划开发我们的两种工具，以遵循与进行性癌相关的遗传变化，从而最终有助于个性化治疗。众所周知，恶性实体瘤在其生长中相对较早的阶段将肿瘤细胞驱散到循环中。因此，如果有可能捕获这些相对罕见的细胞（CTC）并证明它们是恶性的，则可以预期较早的诊断。最近已经描述了捕获具有极高灵敏度的CTC的微芯片。我们已经制作了具有良好灵敏度的微芯片，但使用免疫标准的纳米磁性颗粒改变了它来捕获CTC，然后可以将其释放到一个创新的高光谱成像显微镜（HMI）中，可以在单个通过中准确地量化10个肿瘤标记（TMS）。拟议的CTC芯片-HMI平台可以在不到一个小时的时间内找到血液中的肿瘤标记，并且比现有的（商业）设备（例如细胞轨道）更高的灵敏度和特异性，这是FDA批准的仪器，用于确定基于少量被捕获的CTC的乳腺癌预后和治疗效果。一个主要的突破是证明了癌症细胞对TMS的表达，可以将它们与正常乳腺细胞区分开，而正常乳腺细胞的表达始终较少。因此，在捕获CTC之后，通过HMI评估其TM表达和病理学家关于恶性肿瘤的结论，然后我们可以允许开发TM的数量和程度，而不是表达的数量和程度，从而最大程度地减少了虚假的阳性，但不能以增加虚假负面负数为代价。特定TMS的过度表达的程度和模式对于预后和治疗决策也将具有相当大的价值。我们将研究乳腺癌作为其他癌的原型，这主要是由于可以在射线照相上精确测量恶性肿瘤，并且我们有大量的患者供应。我们计划专注于仪器在小乳腺癌患者中找到CTC的能力。 公共卫生相关性：癌症研究的主要目标是较早诊断该疾病。有大量证据表明，早期诊断癌症可以显着提高治愈率。我们正在以纳米级水平开发设备，该设备将非常有效地捕获循环肿瘤细胞并将其呈现给新型显微镜。新的显微镜将分析这些可疑细胞，并通过过度表达肿瘤标记的含量来确定它们是否是癌细胞。除了早期诊断外，这些肿瘤标记物的表达还将帮助医生预测并确定应向患者进行哪些治疗方法。