BackgroundChemoresistance has long been recognized as a major obstacle in cancer therapy. Clarifying the underlying mechanism of chemoresistance would result in novel strategies to improve patient’s response to chemotherapeutics.MethodslncRNA expression levels in gastric cancer (GC) cells was detected by quantitative real-time PCR (qPCR). MALAT1 shRNAs and overexpression vector were transfected into GC cells to down-regulate or up-regulate MALAT1 expression. In vitro and in vivo assays were performed to investigate the functional role of MALAT1 in autophagy associated chemoresistance.ResultsWe showed that chemoresistant GC cells had higher levels of MALAT1 and increased autophagy compared with parental cells. Silencing of MALAT1 inhibited chemo-induced autophagy, whereas MALAT1 promoted autophagy in gastric cancer cells. Knockdown of MALAT1 sensitized GC cells to chemotherapeutics. MALAT1 acts as a competing endogenous RNA for miR-23b-3p and attenuates the inhibitory effect of miR-23b-3p on ATG12, leading to chemo-induced autophagy and chemoresistance in GC cells.ConclusionsTaken together, our study revealed a novel mechanism of lncRNA-regulated autophagy-related chemoresistance in GC, casting new lights on the understanding of chemoresistance.Electronic supplementary materialThe online version of this article (10.1186/s12943-017-0743-3) contains supplementary material, which is available to authorized users.
BackgroundStandards in treatment of acute cholecystitis (AC) in the elderly and high-risk patients has not been established. Our study evaluated the efficacy and safety of B-mode ultrasound-guided percutaneous transhepatic gallbladder drainage (PTGD) in combination with laparoscopic cholecystectomy (LC) for acute cholecystitis (AC) in elderly and high-risk patients.MethodsOur study enrolled 35 elderly and high-risk AC patients, hospitalized between January 2010 and April 2014 at the Wenzhou People's Hospital. The patients underwent B-mode ultrasound-guided PTGD and LC (PTGD + LC group). As controls, a separate group of 35 elderly and high-risk AC patients who underwent LC alone (LC group) during the same period at the same hospital were randomly selected from a pool of 186 such cases. The volume of bleeding, surgery time, postoperative length of stay, conversion rate to laparotomy and complication rates (bile leakage, bleeding, incisional hernia, incision infection, pulmonary infarction and respiratory failure) were recorded for each patient in the two groups.ResultsAll patients in the PTGD + LC group successfully underwent PTGD. In the PTGD + LC group, abdominal pain in patients was relieved and leukocyte count, alkaline phosphatase level, total bilirubin and carbohydrate antigen 19-9 (CA19-9) decreased to normal range, and alanine aminotransferase and aspartate aminotransferase levels improved significantly within 72 h after treatment. All patients in the PTGD + LC group underwent LC within 6–10 weeks after PTGD. Our study revealed that PTGD + LC showed a significantly higher efficacy and safety compared to LC alone in AC treatment, as measured by the following parameters: duration of operation, postoperative length of hospital stay, volume of bleeding, conversion rate to laparotomy and complication rate (operation time of LC: 55.6 ± 23.3 min vs. 91.35 ± 25.1 min; hospitalized period after LC: 3.0 ± 1.3 d vs. 7.0 ± 1.7 d; intraoperative bleeding: 28.7 ± 15.2 ml vs. 60.38 ± 16.4 ml; conversion to laparotomy: 3 cases vs. 10 cases; complication: 3 cases vs. 8 cases; all P < 0.05 ).ConclusionOur results suggest that B-mode ultrasound-guided PTGD in combination with LC is superior to LC alone for treatment of AC in elderly and high-risk patients, showing multiple advantages of minimal wounding, accelerated recovery, higher safety and efficacy, and fewer complications.
Background : The role of glutathione s-transferase genes ( GSTP1 , GSTM1 and GSTT1 ) variants and the GSTP1 expression level on chemotherapy efficacy of gastrointestinal cancer (GIC) patients were inconsistent. Methods : A meta-analysis about GSTP1 , GSTM1 and GSTT1 variants and the GSTP1 expression level on chemotherapy efficacy of GIC patients was performed using data from PubMed, PMC, EMBASE, Web of Science, and Wanfang database. Results : Our meta-analysis enrolled 50 publications including 6518 patients. We found that patients with GIC harboring GSTP1 (IIe105Val) Val locus had higher objective response rates (ORR) than the IIe/IIe genotypic patients (odds ratio (OR) = 1.580, 95% confidence interval (CI) = 1.159-2.154, P = 0.004). Significant associations were found between the Ile105Val variant and overall survival of Caucasian GIC patients (IIe/Val vs. IIe/IIe: OR = 0.797 (0.674-0.944), P = 0.009). Caucasian GIC patients and gastric cancer patients with GSTT1 null genotype had worse response rates compared to GSTT1 present patients (OR = 0.530 (0.356-0.789), P = 0.002; OR = 0.643 (0.463-0.895), P = 0.009, respectively). Conclusion : This meta-analysis illustrates that GSTP1 IIe105Val and GSTT1 null/present variants could be useful predictors of chemotherapy efficacy in patients with gastrointestinal cancer.
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