scholarly journals Ex Vivo Expansion and Drug Sensitivity Profiling of Circulating Tumor Cells from Patients with Small Cell Lung Cancer

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3394
Author(s):  
Hsin-Lun Lee ◽  
Jeng-Fong Chiou ◽  
Peng-Yuan Wang ◽  
Long-Sheng Lu ◽  
Chia-Ning Shen ◽  
...  

Small cell lung cancer (SCLC) represents one of the most aggressive malignancies among cancer types. Not only tumor sample availability is limited, but also the ability for tumor cells to rapidly acquire drug resistance are the rate-limiting bottlenecks for overall survival in current clinical settings. A liquid biopsy capable of capturing and enriching circulating tumor cells (CTCs), together with the possibility of drug screening, is a promising solution. Here, we illustrate the development of a highly efficient ex vivo CTC expansion system based on binary colloidal crystals substrate. Clinical samples were enrolled from 22 patients with SCLC in the study. The CTCs were enriched and expanded from the collected peripheral blood samples. Expanded cells were analyzed for protein expression and observed for drug sensitivity with the use of immunofluorescence and ATP titer evaluation, respectively. Successful CTC spheroid proliferation was established after 4 weeks within 82% of all the collected peripheral blood samples from enrolled patients. Upon immunofluorescence analysis, the enriched cells showed positive markers for EpCAM, TTF-1, synaptophysin and negative for CD45. Additionally, the expanded CTCs demonstrated marked heterogeneity in the expression of E-cadherin and N-cadherin. In a preliminary case series, the drug sensitivity of patient-derived CTC to cisplatin and etoposide was studied to see the correlation with the corresponding therapeutic outcome. In conclusion, our study demonstrates that it is possible to efficiently expand CTCs from SCLC within a clinically relevant time frame; the biomarker information generated from enriched CTCs can assist the selection of effective drugs and improve disease outcome.

Lung ◽  
2015 ◽  
Vol 193 (3) ◽  
pp. 451-452 ◽  
Author(s):  
Gerhard Hamilton ◽  
Otto Burghuber ◽  
Robert Zeillinger

PLoS ONE ◽  
2017 ◽  
Vol 12 (7) ◽  
pp. e0181211 ◽  
Author(s):  
Ippokratis Messaritakis ◽  
Eleni Politaki ◽  
Athanasios Kotsakis ◽  
Eleftheria-Kleio Dermitzaki ◽  
Filippos Koinis ◽  
...  

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 7592-7592 ◽  
Author(s):  
Satoshi Igawa ◽  
Jiichiro Sasaki ◽  
Noriyuki Masuda

7592 Background: Research on the detection of circulating tumor cells (CTCs) in peripheral blood is currently an important field of research. The aim of this study was to evaluate a new method of detecting CTCs in the peripheral blood of small cell lung cancer (SCLC) patients by using the telomerase-specific replication-selective adenovirus OBP-401. Methods: We prospectively enrolled 30 consecutive newly diagnosed SCLC patients who were being started on chemotherapy or chemoradiotherapy as the subjects of this study. We collected peripheral blood specimens from the SCLC patients and detected viable CTCs in them after incubation with a telomerase-specific, replication-selective, oncolytic adenoviral agent carrying the green fluorescent protein (GFP) gene. We also investigated whether the CTC count per 7.5 ml of peripheral venous blood was associated with the outcome of SCLC. Results: CTCs were detected in 96% of the patients (29 of the 30 patients). The group of 22 patients with a CTC count of < 2 before treatment (baseline) had a significantly longer median survival time than the group of 8 patients with a CTC count of ≥ 2 before treatment (14.8 months and 3.9 months, respectively, P = 0.001). The results of a multivariate analysis showed that the baseline CTC count was an independent prognostic factor for survival (hazard ratio = 5.11, P = 0.038). Conclusions: CTCs in the peripheral blood of SCLC patients can be detected by the OBP-401assay, and based on the results of this study the CTC count before treatment appears to be a strong prognostic factor.


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