Detection of Carcinomas

描述（由申请人提供）：本研究的长期目标是通过血液检查在早期诊断癌症，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仪器，以跟踪与进展性癌相关的基因变化，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就将肿瘤细胞脱落到循环系统中。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，则有望早期诊断。最近已经描述了具有高灵敏度捕获ctc的微芯片。我们已经制造了这样一种微芯片，其灵敏度已得到证实，但我们使用免疫标记的纳米磁性颗粒对其进行了改造，以捕获ctc，然后将其释放到创新的高光谱成像显微镜（HMI）中，该显微镜可以一次精确量化10种肿瘤标志物（TMs）。提出的CTC芯片hmi平台可以在不到一个小时的时间内发现血液中的肿瘤标志物，其灵敏度和特异性比现有（商业）设备（如Cell Tracks）高10倍。Cell Tracks是FDA批准的一种基于少量捕获的CTC来确定乳腺癌预后和治疗效果的仪器。一项重大突破是证明了乳腺癌细胞对TMs的过度表达使其与正常乳腺细胞区分开来，正常乳腺细胞对TMs的过度表达一直较少。因此，在捕获ctc， HMI评估其TM表达以及病理学家关于恶性肿瘤的结论之后，我们可以允许制定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，但不以增加假阴性为代价。特定TMs过表达的程度和模式也将对预后和治疗决策具有相当大的价值。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。我们计划专注于我们的仪器在小乳腺癌患者中发现ctc的能力。

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.