Abstract
// Weiling He 1, 2, ‡ , Di Xu 3, ‡ , Zhuo Wang 1, ‡ , Xianhong Xiang 4, ‡ , Bing Tang 2 , Shuhua Li 1 , Minzhi Hou 1 , Yang Zhang 5 , Jie-Fu Chen 6 , Millicent Lin 6 , Liantang Wang 1 , Shuang Hou 6 , Hsian-Rong Tseng 6 , Ming Kuang 7, * , Zun-fu Ke 1, * 1 Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Province Guangdong, P.R. China 2 Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Province Guangdong, P.R. China 3 Department of Thoracic Surgery, The Central Hospital of Wuhan, Jiang'an District, Wuhan, Hubei Province 430014, P.R. China 4 Department of Interventional Radiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Province Guangdong, P.R. China 5 Biomedical Engineering, University of Texas at El Paso, El Paso, Texas 79968, United States 6 Department of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging (CIMI), California NanoSystems Institute (CNSI), University of California, Los Angeles, California 90095-1770, United States 7 Department of Hepatobiliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Province Guangdong, P.R. China ‡ These authors have contributed equally to this work *Correspondence to: Ming Kuang, e-mail: kuangminda@hotmail.com Zun-fu Ke, e-mail: kezunfu@126.com Keywords: nanomaterials, microfluidics, circulating tumor cell, lung cancer, diagnostics Received: December 06, 2015 Accepted: March 06, 2016 Published: March 23, 2016 ABSTRACT Circulating tumor cells (CTC) shows great prospect to realize precision medicine in cancer patients. We developed the NanoVelcro Chip integrating three functional mechanisms. NanoVelcro CTC capture efficiency was tested in advanced NSCLC. Further, ALK-rearrangement status was examined through fluorescent in situ hybridization in CTCs enriched by NanoVelcro. NanoVelcro system showed higher CTC-capture efficiency than CellSearch in advanced NSCLC. CTC counts obtained by both methods were positively correlated (r=0.45, p<0.05). Further, CTC counts enriched by NanoVelcro correlated to the pTNM stage but CellSearch. All ALK-positive patients had 3 or more ALK-rearranged CTC per mL of blood. Less than 3 ALK-rearranged CTC was detected in ALK-negative patients. NanoVelcro can detect the ALK–rearranged status with consistent sensitivity and specificity compared to biopsy test. Furthermore, the ALK-rearranged CTC ratio correlated to the pTNM stage in ALK-positive patients. Following up with CTC enumeration by NanoVelcro and CellSearch observed their variations in reflecting clinical response of crizotinib treatment. NanoVelcro provides a sensitive method for CTC counts and characterization in advanced NSCLC. ALK-rearrangement can be detected in CTCs collected from advanced NSCLC patients by NanoVelcro, facilitating diagnostic test and prognosis analysis, most importantly offering one noninvasive method for real-time monitoring of treatment reaction.
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