High-purity prostate circulating tumor cell isolation by a polymer nanofiber-embedded microchip for whole exome sequencing.

High-purity prostate circulating tumor cell isolation by a polymer nanofiber-embedded microchip for whole exome sequencing.
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通过聚合物纳米纤维包裹的微芯片进行整个外显子组测序的高纯度前列腺循环肿瘤细胞分离。

DOI:
10.1002/adma.201205237
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发表时间:
2013-06-04
期刊:
影响因子:
29.4
通讯作者:
Posadas, Edwin M.
Posadas, Edwin M.
中科院分区:
材料科学1区
文献类型:
--
作者:
Zhao, Libo;Lu, Yi-Tsung;Li, Fuqiang;Wu, Kui;Hou, Shuang;Yu, Juehua;Shen, Qinglin;Wu, Dongxia;Song, Min;OuYang, Wei-Han;Luo, Zheng;Lee, Tom;Fang, Xiaohong;Shao, Chen;Xu, Xun;Garcia, Mitch A.;Chung, Leland W. K.;Rettig, Matthew;Tseng, Hsian-Rong;Posadas, Edwin M.

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循环肿瘤细胞(Circulating tumor cells,CTC)是存在于外周血中的一种罕见的肿瘤细胞,从实体瘤中分离出来,进入血管系统。[1]尽管CTC产生的机制仍不清楚,但从原发性肿瘤脱落的CTC被认为是理解癌症转移进展起始的关键。[2]除了在癌症生物学中的潜在意义外,它们在癌症诊断、预测治疗反应和研究肿瘤细胞异质性演变方面的临床应用对于临床应用具有更大的重要性。恶性肿瘤具有内在的异质性,这种异质性在疾病进展的整个时间过程中不断演变。因此,通过提供连续且易于获得的肿瘤细胞来源,CTC被认为是原发性和播散性肿瘤的“液体活检”,这可能是全面分子分析和及时监测癌症进展的有希望的替代方案。更重要的是,新一代测序(NGS)技术的最新进展,能够分析微量的遗传物质,甚至达到单细胞水平,这为研究CTC的基因组改变提供了机会。由于缺乏或限制可以表征和/或分离稀有细胞群的技术,与CTC生物学相关的研究一直相对停滞,直到最近。2004年,CellSearch检测试剂盒的开发和随后的FDA批准允许在临床中常规测量CTC。该测定采用能够识别上皮细胞的基于EpCAM的免疫磁性剂,随后进行用于CTC鉴定的多重免疫细胞化学研究。然而,该技术受到其低捕获效率的限制,并且具有有限的捕获后分子分析能力。[3]其他方法主要分为三大类:基于流式细胞术的分选,[4]基于标记蛋白的免疫亲和捕获,[5]和基于大小的分离。[6]这些方法中的许多报道了比目前采用的CellSearch测定更高的CTC捕获效率,但是很少有技术能够表征超出其数量的CTC。CTC的计数并不反映可以提供对肿瘤生物学和异质性的洞察并识别可以真实的指导治疗的驱动突变的分子特征。此外,CTC的分子谱分析可以鉴定新的生物标志物,其可以指导治疗的选择。
Circulating tumor cells (CTCs) are the rare cells found in the peripheral blood, which detached from solid tumors and entered into the vasculature.[1] Although the mechanism of CTC generation is still unclear, CTCs shed from the primary tumor are thought to be the key to understanding the initiation of metastatic progression in cancer.[2] In addition to their potential significance in the cancer biology, their clinical applications in cancer diagnosis, predicting therapeutic responses, and studying the evolution of tumor cell heterogeneity have an even greater importance with respect to clinical applications. It has widely been recognized that the malignant tumors possess intrinsic heterogeneity, which evolves throughout the time course of disease progression. As such, by providing a continuous and readily accessible source of tumor cells, CTCs are regarded as a “liquid biopsy” of the primary and disseminated tumors, which may be a promising alternative for comprehensive molecular profiling and timely monitoring of cancer progression. More importantly, recent advances in next generation sequencing (NGS) technologies, which are capable of profiling minute quantities of genetic materials even to the single cell level, provide an opportunity to investigate the genomic alterations in CTCs.Due to either the absence or limitation of technologies that can characterize and/or isolate rare cell populations, studies relevant to CTC biology have been relatively stagnant until very recently. In 2004, the development and subsequent FDA clearance of the CellSearch assay has allowed for the routine measurement of CTCs in the clinic. This assay employs an EpCAM-based immunomagnetic agent capable of recognizing epithelial cells followed by subsequent multiplexed immunocytochemistry studies for CTC identification. This technology, however, is constrained by its low capture efficiency and has limited ability for post-capture molecular analysis.[3] Other approaches fall mostly into one of the three main categories: flow cytometry-based sorting,[4] marker protein-based immunoaffinity capture,[5] and size-based isolation.[6] Many of these approaches reported higher CTC capture efficiencies than the currently employed CellSearch assay, but few technologies enable the characterization of CTCs beyond their number. Enumeration of CTCs does not reflect the molecular signatures that can provide insights into tumor biology and heterogeneity and identify driver mutations that can guide therapy in real time. Moreover, the molecular profiling of CTCs may identify novel biomarkers that could guide the choice of therapies for
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