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）：这项研究的长期目标是通过早期血液检查诊断癌症，从而提高治愈率。在这个项目中，我们将重点开发两种仪器来跟踪与进展性癌症相关的基因变化，从而最终帮助个性化治疗。众所周知，恶性实体瘤在其生长的相对早期阶段将肿瘤细胞释放到循环中。因此，如果能够捕获这些相对稀有的细胞（CTC）并证明它们是恶性的，则有望实现早期诊断。最近描述了能够以高灵敏度捕获 CTC 的微芯片。我们已经制造了这种具有经过验证的灵敏度的微芯片，但使用免疫标记的纳米磁性颗粒对其进行了更改，以捕获 CTC，然后将其释放到创新的高光谱成像显微镜 (HMI)，该显微镜可以一次性精确量化 10 种肿瘤标志物 (TM)。拟议的 CTC 芯片-HMI 平台可以在不到一小时的时间内找到血液中的肿瘤标志物，其灵敏度和特异性比现有（商业）设备（例如 Cell Tracks）高 10 倍，Cell Tracks 是 FDA 批准的一种仪器，用于确定癌症患者的预后和治疗效果。基于极少数捕获的 CTC 的乳腺癌。一项重大突破是证明乳腺癌细胞过度表达TMs，使其能够与正常乳腺细胞区分开来，而正常乳腺细胞的TMs过度表达始终较少。因此，在捕获 CTC、通过 HMI 评估其 TM 表达以及病理学家关于恶性肿瘤的结论后，我们可以制定 TM 过度表达的数量和程度的标准，以最大限度地减少假阳性，但不会以牺牲增加假阴性。特定 TM 过度表达的程度和模式对于预后和治疗决策也具有相当大的价值。我们将把乳腺癌作为其他癌症的原型来研究，主要是因为恶性肿瘤可以通过放射学精确测量，而且我们有大量的患者供应。我们计划重点关注我们的仪器在小乳腺癌患者中发现 CTC 的能力。 公共卫生相关性：癌症研究的一个主要目标是早期诊断疾病。有大量证据表明癌症的早期诊断可以显着提高治愈率。我们正在开发纳米级的设备，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，并通过其过度表达的肿瘤标志物的含量来确定它们是否是癌细胞。除了早期诊断之外，这些肿瘤标志物的表达将帮助医生预测并确定应该对患者进行哪些治疗。