Detection of Carcinomas

描述(申请人提供)：这项研究的长期目标是通过早期血液测试来诊断癌症，从而提高治愈率。在这个项目中，我们将专注于开发我们的两种工具，以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，恶性实体瘤在肿瘤细胞生长的相对早期阶段就将其释放到血液循环中。因此，如果有可能捕获这些相对罕见的细胞(CTCs)并证明它们是恶性的，那么就有望得到更早的诊断。最近已经描述了以极高的灵敏度捕获CTCs的微芯片。我们已经制造了这样一个被证明具有灵敏度的微芯片，但已经使用免疫可标记纳米磁性颗粒来捕获CTCs，然后将其发布到创新的高光谱成像显微镜(HMI)中，该显微镜可以一次精确地定量10个肿瘤标志物(TM)。拟议的CTC芯片-HMI平台可以在不到一小时的时间内在血液中找到肿瘤标志物，其灵敏度和特异度比现有(商业)设备(如Cell Track)高10倍，Cell Track是FDA批准的一种基于非常少量捕获的CTC来确定乳腺癌预后和治疗效果的仪器。一个重大突破是证明了癌细胞过度表达TMS使它们与正常乳腺细胞区分开来，正常乳腺细胞持续较少过度表达TMS。因此，在捕获CTC、通过HMI评估它们的TM表达以及病理学家关于恶性肿瘤的结论之后，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，但不会以增加假阴性为代价。特定TMS过度表达的程度和模式对预后和治疗决策也有相当大的价值。我们将研究乳腺癌作为其他癌症的原型，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。我们计划将重点放在我们的仪器在小乳腺癌患者中发现CTC的能力上。

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.