RESUMEN
Liver cancer is a leading cause of cancer-related deaths globally. Tumor response rate of liver cancer patients towards systemic chemotherapy is low and chemoresistance can easily develop. Identifying novel molecules that can repress drug resistance and metastasis of liver cancer will facilitate the development of new therapeutic strategies. The aim of this study is to determine the roles of NUAK1 and miR-204 in the drug resistance and metastasis of liver cancer and to reveal their relationship. We found that NUAK1 was increased in the tumor of primary liver cancer. Knockdown of NUAK1 significantly inhibited cell growth and migration. Moreover, NUAK1 was the direct downstream target of miR-204, and there was clinical relevance between miR-204 down-regulation and NUAK1 up-regulation in liver cancer. Furthermore, we found that miR-204 increased drug sensitivity by down-regulating NUAK1 expression. Based on these results, we identified miR-204 as a tumor suppressor by inhibiting NUAK1 expression in liver cancer, indicating both miR-204 and NUAK1 may act as promising targets for liver cancer therapy.
Asunto(s)
Antineoplásicos/farmacología , Carcinoma Hepatocelular/tratamiento farmacológico , Resistencia a Antineoplásicos/efectos de los fármacos , Neoplasias Hepáticas/tratamiento farmacológico , MicroARNs/farmacología , Proteínas Represoras/antagonistas & inhibidores , Antineoplásicos/química , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , MicroARNs/química , Proteínas Quinasas/metabolismo , Proteínas Represoras/metabolismo , Relación Estructura-Actividad , Células Tumorales CultivadasRESUMEN
BACKGROUND: The purpose of this study was to investigate the effect of a simple laparoscopic common bile duct exploration (LCBDE) simulator and corresponding practicing program on the application of performing LCBDE in a low volume center. METHODS: A retrospective review was performed by analyzing data from the electronic medical record for 4118 patients with choledocholithiasis in Changxing County Hospital (Huzhou, Zhejiang, China) between January 2013 and December 2018. From January 2016, we have developed a simple LCBDE-specific simulator and corresponding practicing program in our hospital. The percentage of patients with choledocholithiasis managed by LCBDE before and after the introduction of a simple LCBDE-specific simulator and corresponding practicing program was compared. RESULTS: There were 8.9% (367/4118) patients with a diagnosis of choledocholithiasis confirmed by MRCP. Single-stage management with LC+LCBDE was performed in 23.7% (87/367) patients. Among them, 23 cases were performed between January 2013 and December 2015, and 64 cases were performed between January 2016 and December 2018. The introduction of simulator-enhanced practicing program in January 2016 has resulted in an increase in the percentage of performed LCBDE, from 12.9% to 33.9%. In addition, there was an 29.5% reduction in the mean operating time (from 193 min to 136 min) needed for LCBDE with T-tube when compared these two periods. CONCLUSIONS: LCBDE simulator can improve the application in a low volume center, and help to increase the utilization of this effective, one stage treatment for choledocholithiasis and reduce the need for costlier ERCP.