Phenotype-related drug sensitivity analysis of single CTCs for medicine evaluation.
Phenotype-related drug sensitivity analysis of single CTCs for medicine evaluation.
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用于药物评价的单一 CTC 表型相关药物敏感性分析
DOI：
10.1039/c9sc05566e
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发表时间：
2020-08-10
期刊：
影响因子：
8.4
通讯作者：
Tang B
中科院分区：
文献类型：
--
作者：
Pei H;Yu M;Dong D;Wang Y;Li Q;Li L;Tang B
由于肿瘤细胞的药物敏感性具有异质性和多变性，因此实时监测患者的药物反应是实现个性化和动态治疗的必要条件。尽管在活细胞中进行药物筛选方面已经做出了相当大的努力，但在单细胞水平上使用患者来源的原发肿瘤细胞进行重复的药物敏感性分析仍然具有挑战性。在这里，我们提出了一种基于药物敏感性微流控芯片（DS-Chip）的单细胞水平评估表型相关药物敏感性的有效方法，该方法使用患者来源的循环肿瘤细胞（ctc）。DS-Chip由药物梯度发生器和平行细胞陷阱组成，可实现连续的单CTC捕获、药物梯度分布、药物刺激、荧光探针标记和三色荧光成像。基于建立的DS-Chip，我们通过同时监测活细胞上皮间充质转化（epithelial-mesenchymal transition， EMT）生物标志物和细胞凋亡来研究单个细胞的药物敏感性，验证EMT梯度与药物敏感性的相关性。利用这种新方法，我们通过荧光分析EMT和细胞凋亡，进一步测试了5例癌症患者个体ctc的最佳药物反应剂量。DS-Chip允许在治疗期间对患者肿瘤细胞的药物敏感性进行无创和实时测量。该方法具有实际意义，可有效指导个体化医疗的药物选择和治疗评价。由于肿瘤细胞的药物敏感性具有异质性和多变性，因此实时监测患者的药物反应是实现个性化和动态治疗的必要条件。
Due to the heterogeneous and variable drug sensitivity of tumor cells, real-time monitoring of a patient's drug response is desirable for implementing personalized and dynamic therapy. Although considerable efforts have been directed at drug screening in living cells, performing repeated drug sensitivity analysis using patient-derived primary tumor cells at the single-cell level remains challenging. Here, we present an efficient approach to assess phenotype-related drug sensitivity at the single-cell level using patient-derived circulating tumor cells (CTCs) based on a drug sensitivity microfluidic chip (DS-Chip). The DS-Chip consists of a drug gradient generator and parallel cell traps, achieving continuous single CTC capture, drug gradient distributions, drug stimulation, fluorescent probe labeling and three-color fluorescence imaging. Based on the established DS-Chip, we investigated the drug sensitivity of single cells by simultaneously monitoring epithelial–mesenchymal transition (EMT) biomarkers and apoptosis in living cells, and verified the correlation between EMT gradients and drug sensitivity. Using the new approach, we further tested the optimal drug response dose in individual CTCs isolated from 5 cancer patients through fluorescence analysis of EMT and apoptosis. The DS-Chip allows noninvasive and real-time measurements of the drug sensitivity of a patient's tumor cells during therapy. This developed approach has practical significance and can effectively guide drug selection and therapeutic evaluation for personalized medicine. Due to the heterogeneous and variable drug sensitivity of tumor cells, real-time monitoring of a patient's drug response is desirable for implementing personalized and dynamic therapy.
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快速，敏感和定量的护理平台，用于评估尿液，血清和全血的滥用药物。
影响因子：
7.4
作者：
Li Y;Uddayasankar U;He B;Wang P;Qin L
通讯作者：
Qin L
影响因子：
16.6
作者：
Chia S;Low JL;Zhang X;Kwang XL;Chong FT;Sharma A;Bertrand D;Toh SY;Leong HS;Thangavelu MT;Hwang JSG;Lim KH;Skanthakumar T;Tan HK;Su Y;Hui Choo S;Hentze H;Tan IBH;Lezhava A;Tan P;Tan DSW;Periyasamy G;Koh JLY;Gopalakrishna Iyer N;DasGupta R
通讯作者：
DasGupta R
影响因子：
38.3
作者：
Poudineh, Mahla;Aldridge, PeterM.;Kelley, Shana O.
通讯作者：
Kelley, Shana O.
影响因子：
64.8
作者：
Garnett, Mathew J.;Edelman, Elena J.;Heidorn, Sonja J.;Greenman, Chris D.;Dastur, Anahita;Lau, King Wai;Greninger, Patricia;Thompson, I. Richard;Luo, Xi;Soares, Jorge;Liu, Qingsong;Iorio, Francesco;Surdez, Didier;Chen, Li;Milano, Randy J.;Bignell, Graham R.;Tam, Ah T.;Davies, Helen;Stevenson, Jesse A.;Barthorpe, Syd;Lutz, Stephen R.;Kogera, Fiona;Lawrence, Karl;McLaren-Douglas, Anne;Mitropoulos, Xeni;Mironenko, Tatiana;Thi, Helen;Richardson, Laura;Zhou, Wenjun;Jewitt, Frances;Zhang, Tinghu;O'Brien, Patrick;Boisvert, Jessica L.;Price, Stacey;Hur, Wooyoung;Yang, Wanjuan;Deng, Xianming;Butler, Adam;Choi, Hwan Geun;Chang, JaeWon;Baselga, Jose;Stamenkovic, Ivan;Engelman, Jeffrey A.;Sharma, Sreenath V.;Delattre, Olivier;Saez-Rodriguez, Julio;Gray, Nathanael S.;Settleman, Jeffrey;Futreal, P. Andrew;Haber, Daniel A.;Stratton, Michael R.;Ramaswamy, Sridhar;McDermott, Ultan;Benes, Cyril H.
通讯作者：
Benes, Cyril H.
DOI：
10.1126/science.1228522
发表时间：
2013-02-01
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Yu M;Bardia A;Wittner BS;Stott SL;Smas ME;Ting DT;Isakoff SJ;Ciciliano JC;Wells MN;Shah AM;Concannon KF;Donaldson MC;Sequist LV;Brachtel E;Sgroi D;Baselga J;Ramaswamy S;Toner M;Haber DA;Maheswaran S
通讯作者：
Maheswaran S