Plasma microRNA-based signatures to predict 3-year postoperative recurrence risk for stage II and III gastric cancer.

Our aim was to identify plasma microRNA (miRNA)-based signatures to predict 3-year postoperative recurrence risk for patients with stage II and III gastric cancer (GC), so as to provide insights for individualized adjuvant therapy. Plasma miRNA expression was investigated in three phases, involving 407 patients recruited from three centers. ABI miRNA microarray and TaqMan Low Density Array were adopted in the discovery phase to identify potential miRNAs. Quantitative reverse-transcriptase polymerase chain reaction was used to assess the expression of selected miRNAs. Logistic regression models were constructed in the training set (n = 170) and validated in the validation set (n = 169). Receiver operating characteristic analyses, survival analyses and subgroup analyses were further used to assess the accuracy of the models. We identified a 7 miRNA classifier and 7miR + pathological factors index that provided high predictive accuracy of GC recurrence (area under the curve = 0.725 and 0.841 in the training set; and 0.627 and 0.771 in the validation set). High-risk patients defined by the signatures had significantly shorter disease-free survival and overall survival than low-risk patients. The 7 miRNA classifier is an independent prognostic factor, and could add predictive value to traditional prognostic factors. Subgroup analyses revealed the satisfactory performance persisted regardless of stage, and the two models both displayed high accuracy in stage IIA patients. In conclusion, identified microRNA signature may potentially provide some additional benefit for prediction of disease recurrence in patients with stage II and III GC.

Clinical application of dexmedetomidine combined with dezocine in local anesthesia for endoscopic dacryocystorhinostomy.

OBJECTIVE: To investigate the clinical effect of dexmedetomidine combined with dezocine in local anesthesia for endoscopic dacryocystorhinostomy (DCR). METHODS: Ninety patients undergoing elective endoscopic DCR were randomly divided into two groups, local anesthesia group (LA group n = 45) and general anesthesia group (GA group, n = 45). These subjects were all American Society of Anesthesiologists (ASA)-Physical Status I-II patients. The changes of mean arterial pressure (MAP) and heart rate (HR) were observed and recorded before anesthesia (T0), after anesthesia (T1), at the beginning of surgery (T2), and at the end of surgery (T3). The visual analogue scale (VAS) score was observed and recorded immediately after awakening from anesthesia and at 1, 2, 6, and 12 h after surgery. Additionally, the occurrence of adverse reactions after surgery and the sedation-agitation scale (SAS) score after awakening were recorded. RESULTS: Compared with the LA group, the MAP and HR of the GA group were significantly lower at T1 and T2, but significantly higher at T3. Local anesthesia was associated with lower VAS score immediately after awakening and at 1, 2, 6, and 12 h after surgery. Also, local anesthesia caused a lower incidence of postoperative agitation, nausea, and vomiting. The SAS score in the LA group was markedly higher than that in the GA group. CONCLUSION: Local anesthesia with dexmedetomidine and dezocine as adjuvants in endoscopic DCR has more stable hemodynamics and reduces the stress response during perioperative period. Also, this anesthesia achieves better postoperative sedation and analgesia effects, reduces postoperative complications, and improves the quality of awakening from anesthesia. Collectively, local anesthesia is a comfortable and safe option for patients with high risks of general anesthesia and those unwilling to receive general anesthesia.

The combination of RAD001 and MK-2206 exerts synergistic cytotoxic effects against PTEN mutant gastric cancer cells: involvement of MAPK-dependent autophagic, but not apoptotic cell death pathway.

In the current study, we showed that the combination of mammalian target of rapamycin (mTOR) inhibitor RAD001 (everolimus) and Akt inhibitor MK-2206 exerted synergistic cytotoxic effects against low-phosphatase and tensin homolog (PTEN) gastric cancer cells (HGC-27 and SNU-601 lines). In HGC-27 cells, RAD001 and MK-2206 synergistically induced G1/S cell cycle arrest, growth inhibition, cell death but not apoptosis. RAD001 and MK-2206 synergistically induced light chain 3B (LC3B) and beclin-1 expression, two important autophagy indicators. Meanwhile, the autophagy inhibitor 3-methyladenine (3-MA) and chloroquine inhibited the cytotoxic effects by RAD001 and MK-2206, suggesting that autophagic, but not apoptotic cell death was important for the cytotoxic effects by the co-administration. We observed that the combination of RAD001 and MK-2206 exerted enhanced effects on Akt/mTOR inhibition, cyclin D1 down-regulation and ERK/MAPK(extracellular signal-regulated kinase/mitogen-activated protein kinases) activation. Intriguingly, MEK/ERK inhibitors PD98059 and U0126 suppressed RAD001 plus MK-2206-induced beclin-1 expression, autophagy induction and cytotoxicity in HGC-27 cells. In conclusion, these results suggested that the synergistic anti-gastric cancer cells ability by RAD001 and MK-2206 involves ERK-dependent autophagic cell death pathway.