Oncotarget
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Papillary thyroid carcinoma (PTC) is the most frequent endocrine tumor. BRAFV600E represents the PTC hallmark and is targeted with selective inhibitors (e.g. vemurafenib). Although there have been promising results in clinical trials using these inhibitors, most patients develop resistance and progress. Tumor clonal diversity is proposed as one mechanism underlying drug resistance. Here we have investigated mechanisms of primary and secondary resistance to vemurafenib in BRAFWT/V600E-positive PTC patient-derived cells with P16-/- (CDKN2A-/-). ⋯ Critically, our findings suggest for the first time that targeting BRAFWT/V600E and CDK4/6 represents a novel therapeutic strategy to treat vemurafenib-resistant or vemurafenib-naïve radioiodine-refractory BRAFWT/V600E-PTC. This combined therapy could prevent selection and expansion of aggressive PTC cell sub-clones with intrinsic resistance, targeting tumor cells either with primary or secondary resistance to BRAFV600E inhibitor.
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Perioperative immunonutrition in liver resection remains doubtful. A systematic review and meta-analysis was conducted to compare postoperative outcomes between patients undergoing hepatectomy who received perioperative immunonutrition and those who did not. A PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Knowledge database search was performed to retrieve all of the randomized controlled trials (RCTs) evaluating the value of perioperative immunonutrition in patients undergoing hepatectomy until the end of September 2016. ⋯ Immunonutrition, mainly ω-3 fatty acids, significantly reduced the incidence of postoperative total complications (risk ratio [RR] = 0.59; 95% confidence interval [CI], 0.46-0.75; p < 0.0001) and infectious complications (RR = 0.46; 95% CI, 0.32-0.68; p < 0.0001), and shortened the length of hospital stay (standardized mean difference, -0.49; 95% CI, -0.81 to -0.16; p = 0.0004). There was no significant between-group difference in postoperative mortality (RR = 0.46; 95% CI, 0.16-1.31; p = 0.15). Immunonutrition, mainly ω-3 fatty acids, is potentially beneficial in reducing overall and infectious postoperative complications and in shortening the hospital stay for patients undergoing hepatectomy.
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This study assessed whether combining adipose-derived mesenchymal stem cells (ADMSC) with preactivated, disaggregated shape-changed platelets (PreD-SCP) was superior to either therapy alone for protecting rat lung from acute respiratory distress syndrome (ARDS) complicated by sepsis. ARDS and sepsis were induced through 100% oxygen inhalation and peritoneal administration of 1.5 mg/kg lipopolysaccharide (LPS), respectively. Adult-male Sprague-Dawley rats (n=40) were randomized into sham-control (SC), ARDS-LPS, ARDS-LPS-ADMSC (1.2x106 cells), ARDS-LPS-PreD-SCP (3.0x108, intravenous administration), and ARDS-LPS-ADMS/PreD-SCP groups, and were sacrificed 72 h after 48 h ARDS induction. ⋯ Levels of inflammatory, oxidative-stress, apoptosis, mitochondrial/DNA damage, and MAPK and Akt signaling markers exhibited patterns identical to that of LIS (all p<0.001). Anti-oxidant and anti-inflammatory protein levels increased progressively from SC to ARDS-LPS+ADMS/PreD-SCP (all p<0.0001). These findings indicate combined ADMSC/PreD-SCP was superior to either therapy alone for protecting rat lung from ARDS-sepsis injury.
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There are currently 2 Tumour-Node-Metastasis (TNM) staging systems for pancreatic neuroendocrine tumours (p-NETs) - European Neuroendocrine Tumour Society (ENETS) and American Joint Committee on Cancer (AJCC). P-NETs being heterogeneous, we investigated the prognostic value of the 2 systems in p-NETs, as a whole, and more interestingly in functional and non-functional sub-groups separately, with a view to ascertaining any potential clinical benefits of using one system over the other. ⋯ The ENETS system might have potential advantages when applied to all p-NETs and to the functional sub-group, while the AJCC system might be clinically more practical for non-functional p-NETs.
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New-onset atrial fibrillation (NOAF) occurs frequently in patients with acute myocardial infarction (AMI), and is associated with increased subsequent cardiovascular mortality. However, only a few studies directly evaluated the relationship of left ventricular ejection fraction (LVEF) or left atrium diameter (LAD) and NOAF following AMI. ⋯ Our meta-analysis demonstrated that both decreased LVEF and increased LAD levels were associated with greater risk of NOAF following AMI.