PMID- 31504065 OWN - NLM STAT- MEDLINE DCOM- 20200305 LR - 20221207 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 14 IP - 9 DP - 2019 TI - In vitro and molecular chemosensitivity in human cholangiocarcinoma tissues. PG - e0222140 LID - 10.1371/journal.pone.0222140 [doi] LID - e0222140 AB - Adjuvant chemotherapy is required for cholangiocarcinoma (CCA) patients after surgical treatment. Gemcitabine and gemcitabine plus cisplatin are considered the appropriate regimen; however, the response spectrum to chemotherapy differs between patients. Thus, the present study aims to evaluate the response pattern of individual CCA patients by using an in vitro method, histoculture drug response assay (HDRA), to predict the chemosensitivity of individual patients in a prospective study. Moreover, we also investigate the expression of gemcitabine and cisplatin sensitivity factors in CCA tissues in the same cases. Based on the dose response curve, 1000 and 1500 mug/ml of gemcitabine were used as the testing concentrations. For cisplatin, concentrations of 20 and 25 mug/ml were selected for testing and for the combination regimen, 1000 mug/ml of gemcitabine and 20 mug/ml of cisplatin were chosen. The median %IR of each drug was measured as the cut-off to categorize the response pattern into response and non-response groups. In addition, we compared the effectiveness of the chemotherapy regimens between gemcitabine alone and gemcitabine plus cisplatin. The %IR of the combination of gemcitabine and cisplatin was significantly higher than gemcitabine alone. The relationship between the expression level of gemcitabine and cisplatin sensitive factors and the individual response pattern as well as clinicopathological data of CCA patients were analyzed. The results indicated that a low expression of the gemcitabine sensitive factor hENT-1 was significantly associated with the non-response group in vitro (p = 0.002). Moreover, the low expression of hENT-1 was also significantly associated with advanced stages CCA in the patients (p = 0.025). A low expression of MT and ERCC1 was significantly correlated with the response group in the in vitro experiments (p = 0.015 and p = 0.037 for MT and ERCC1, respectively). Therefore, HDRA may serve as an aid to selecting chemotherapy, and the expression of hNET-1, MT and ERCC1 may serve as biomarkers for predicting chemotherapy success. FAU - Suksawat, Manida AU - Suksawat M AD - Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. AD - Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand. FAU - Klanrit, Poramate AU - Klanrit P AUID- ORCID: 0000-0003-0209-3901 AD - Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. AD - Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand. AD - Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand. FAU - Phetcharaburanin, Jutarop AU - Phetcharaburanin J AD - Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. AD - Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand. AD - Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand. FAU - Namwat, Nisana AU - Namwat N AD - Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. AD - Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand. AD - Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand. FAU - Khuntikeo, Narong AU - Khuntikeo N AD - Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand. AD - Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand. AD - Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. FAU - Titapun, Attapol AU - Titapun A AD - Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand. AD - Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand. AD - Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. FAU - Jarearnrat, Apiwat AU - Jarearnrat A AD - Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand. AD - Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand. AD - Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. FAU - Sa-Ngiamwibool, Prakasit AU - Sa-Ngiamwibool P AD - Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand. AD - Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand. AD - Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. FAU - Techasen, Anchalee AU - Techasen A AD - Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand. AD - Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand. AD - Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand. FAU - Loilome, Watcharin AU - Loilome W AUID- ORCID: 0000-0001-8572-5577 AD - Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. AD - Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand. AD - Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190910 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Antineoplastic Agents) RN - 0W860991D6 (Deoxycytidine) RN - Q20Q21Q62J (Cisplatin) RN - 0 (Gemcitabine) SB - IM MH - Aged MH - Antineoplastic Agents/toxicity MH - Cholangiocarcinoma/*drug therapy/pathology MH - Cisplatin/toxicity MH - Deoxycytidine/analogs & derivatives/toxicity MH - *Drug Resistance, Neoplasm MH - Female MH - Humans MH - Male MH - Middle Aged MH - Tissue Culture Techniques/*methods MH - Toxicity Tests/methods MH - Gemcitabine PMC - PMC6736243 COIS- The authors have declared that no competing interests exist. EDAT- 2019/09/11 06:00 MHDA- 2020/03/07 06:00 PMCR- 2019/09/10 CRDT- 2019/09/11 06:00 PHST- 2019/06/14 00:00 [received] PHST- 2019/08/22 00:00 [accepted] PHST- 2019/09/11 06:00 [entrez] PHST- 2019/09/11 06:00 [pubmed] PHST- 2020/03/07 06:00 [medline] PHST- 2019/09/10 00:00 [pmc-release] AID - PONE-D-19-16909 [pii] AID - 10.1371/journal.pone.0222140 [doi] PST - epublish SO - PLoS One. 2019 Sep 10;14(9):e0222140. doi: 10.1371/journal.pone.0222140. eCollection 2019.