Activated Protein C Induces Endoplasmic Reticulum Stress and Attenuates Lipopolysaccharide-Induced Apoptosis Mediated by Glycogen Synthase Kinase-3β

This study investigated the relationship between antiapoptotic activities induced by activated protein C and endoplasmic reticulum stress. In this study, it was observed that activated protein C elicited a rise in glucose-regulated protein 78 and glycogen synthase kinase-3β and inhibited apoptosis in human umbilical vein endothelial cells induced by lipopolysaccharide. Calcium inhibition did not alter the antiapoptotic effect of activated protein C. The antiapoptotic efficiency of activated protein C was reduced in human umbilical vein endothelial cells following treatment with glycogen synthase kinase-3β-siRNA. In summary, activated protein C induced endoplasmic reticulum stress and attenuated lipopolysaccharide-induced human umbilical vein endothelial cell apoptosis mediated by glycogen synthase kinase-3β

Prognostic value of lymph node ratio in patients with pathological N1 non-small cell lung cancer: A systematic review with meta-analysis

Background: Non-small cell lung cancer (NSCLC) patients with N1 disease have variable outcomes, and additional prognostic factors are needed. The number of positive lymph nodes (LNs) has been proposed as a prognostic indicator. However, the number of positive LNs depends on the number of LNs examined from the resection specimen. The lymph node ratio (LNR) can circumvent this limitation. The purpose of this study is to evaluate LNR as a predictor of survival and recurrence in patients with pathologic N1 NSCLC. Methods: We systematically reviewed studies published before March 17, 2016, on the prognostic value of LNR in patients with pathologic N1 NSCLC. The hazard ratios (HRs) and their 95% confidence intervals (CIs) were used to combine the data. We also evaluated heterogeneity and publication bias. Results: Five studies published between 2010 and 2014 were eligible for this systematic review with metaanalysis. The total number of patients included was 6,130 ranging from 75 to 4,004 patients per study. The combined HR for all eligible studies evaluating the overall survival (OS) and disease-free survival (DFS) of N1 LNR in patients with pathologic N1 NSCLC was 1.53 (95% CI: 1.22-1.85) and 1.64 (95% CI: 1.19-2.09), respectively. We found no heterogeneity and publication bias between the reports. Conclusions: LNR is a worthy predictor of survival and cancer recurrence in patients with pathological N1 NSCLC

Over-Expression of LSD1 Promotes Proliferation, Migration and Invasion in Non-Small Cell Lung Cancer

Background: Lysine specific demethylase 1 (LSD1) has been identified and biochemically characterized in epigenetics, but the pathological roles of its dysfunction in lung cancer remain to be elucidated. The aim of this study was to evaluate the prognostic significance of LSD1 expression in patients with non-small cell lung cancer (NSCLC) and to define its exact role in lung cancer proliferation, migration and invasion. Methods: The protein levels of LSD1 in surgically resected samples from NSCLC patients were detected by immunohistochemistry or Western blotting. The mRNA levels of LSD1 were detected by qRT-PCR. The correlation of LSD1 expression with clinical characteristics and prognosis was determined by statistical analysis. Cell proliferation rate was assessed by MTS assay and immunofluorescence. Cell migration and invasion were detected by scratch test, matrigel assay and transwell invasion assay. Results: LSD1 expression was higher in lung cancer tissue more than in normal lung tissue. Our results showed that overexpression of LSD1 protein were associated with shorter overall survival of NSCLC patients. LSD1 was localized mainly to the cancer cell nucleus. Interruption of LSD1 using siRNA or a chemical inhibitor, pargyline, suppressed proliferation, migration and invasion of A549, H460 and 293T cells. Meanwhile, over-expression of LSD1 enhanced cell growth. Finally, LSD1 was shown to regulate epithelial-to-mesenchymal transition in lung cancer cells

Expression and Prognostic Value of AKT2 in Non-small Cell Lung Cancer

Background and objective AKT2 is a critical actor in the PI3K signal transduction pathway. Activation of AKT2 can lead to cell growth and survival. It has been revealed that AKT2 play a central role in tumorigenesis, tumor growth as well as metastasis. The aim of this study is to investigate the association between AKT2 and the clinical outcome of non-small cell lung cancer (NSCLC) patients by detecting its expression levels in the tumor tissue samples. Methods We developed an immunohistochemistry (IHC) assay to measure AKT2 protein levels in lung specimens from 80 cases with NSCLC and 10 cases with benign pulmonary disease. Results The positive rate of AKT2 was 57.50% (46/80) in NSCLC, which was higher than that in benign pulmonary (10.0%) samples (χ2=8.038, P=0.006). There was no significant correlation between AKT2 expression and the clinicopathologic profiles. The expression of AKT2 was significantly correlated with the progression free survival (PFS) ( χ2=12.671, P=0.005) and the overall survival (OS) (χ2=9.851, P=0.021) of patients with NSCLC. Conclusion AKT2 may provide a prognostic bio-marker of NSCLC

Expression of KIF23 and Its Prognostic Role in Non-small Cell Lung Cancer: Analysis Based on the Data-mining of Oncomine

Background and objective Non-small cell lung cancer (NSCLC) is one of the most common cause of cancer-related death worldwide. As the overall prognosis for affected patients is still poor, there is a need for biomarkers for prediction of survival and guiding individual therapy. This study is to explore the expression and significance of kinesin family member 23 (KIF23) in NSCLC. Methods KIF23 data were retrieved from Oncomine NSCLC database. The prognostic value of KIF23 was retrieved from an online survival analysis tool “Kaplan-Meier Plotter” (KM plotter) database. Results In Oncomine database, there were 447 studies of different types concerning expression of KIF23, of which 67 studies were of statistically significance (64 up-regulated and 3 down-regulated). A total of 16 studies were involved KIF23 in NSCLC tissues and normal tissues, including a total of 1,189 samples. Overall, KIF23 expression in NSCLC is higher than that in normal tissues (P<0.05). Moreover, Kaplan-Meier plots of overall survival indicated that KIF23 high expression is closely associated with poor survival in NSCLC (P<0.05). Subgroup analysis revealed that KIF23 expression showed negative relation to the prognosis of pulmonary adenocarcinoma patients. Whereas, in those with squamous carcinoma KIF23 expression showed no effects on the prognosis of the patients. Conclusion KIF23 was found highly expressed in NSCLC, which might be a marker for NSCLC prognosis

The plasma mitochondrial DNA is an independent predictor for post-traumatic systemic inflammatory response syndrome.

BACKGROUND AND PURPOSE: Mitochondrial DNA (mtDNA), a newly identified damage-associated molecular pattern, has been observed in trauma patients, however, little is known concerning the relationship between plasma mtDNA levels and concrete post-traumatic complications, particularly systemic inflammatory response syndrome (SIRS). The aim of this study is to determine whether plasma mtDNA levels are associated with injury severity and cloud predict post-traumatic SIRS in patients with acute traumatic injury. PATIENTS AND METHODS: Eighty-six consecutive patients with acute traumatic injury were prospectively enrolled in this study. The plasma mtDNA concentration was measured by a real-time, quantitative PCR assay for the human ND2 gene. The study population's clinical and laboratory data were analyzed. RESULTS: The median plasma mtDNA was higher in trauma patients than in healthy controls (865.196 (251.042-2565.40)pg/ml vs 64.2147 (43.9049-80.6371)pg/ml, P<0.001) and was independently correlated with the ISS score (r=0.287, P<0.001). The plasma mtDNA concentration was also significantly higher in patients who developed post-traumatic SIRS than in patients who did not (1774.03 (564.870-10901.3)pg/ml vs 500.496 (145.415-1285.60)pg/ml, P<0.001). Multiple logistic regression analysis revealed that the plasma mtDNA was an independent predictors for post-traumatic SIRS (OR, 1.183 (95%CI, 1.015-1.379), P=0.032). Further ROC analysis demonstrated that a high plasma mtDNA level predicted post-traumatic SIRS with a sensitivity of 67% and a specificity of 76%, with a cut-off value of 1.3185 µg/ml being established, and the area under the ROC curves (AUC) was 0.725 (95% CI 0.613-0.837). CONCLUSIONS: Plasma mtDNA was an independent indictor with moderate discriminative power to predict the risk of post-traumatic SIRS

Circulating Tumor Cells Were Associated with the Number of T Lymphocyte Subsets and NK Cells in Peripheral Blood in Advanced Non-Small-Cell Lung Cancer

In this study, we aim to investigate the correlation between circulating tumor cells (CTCs) and the T lymphocyte subsets and NK cells in peripheral blood in non-small-cell lung cancer (NSCLC). The peripheral blood CTCs were determined by SET-iFISH. Flow cytometry was used to determine the distribution of T lymphocyte subsets and NK cells. Forty-one (49%) patients showed positivity for CTCs. Logistic regression analysis revealed CTC number was negatively correlated with the ratio of CD3+, CD4+, CD4+/CD8+, and NK % in patients at stage IV, while in a positive correlation was noticed between CTC number and regulatory T cell (Tregs) ratio in these patients. Multivariate analysis was performed in combination with the clinical-pathological materials to identify the risk factors for CTC positivity. Differentiation, NSCLC stage, percentages of CD3+CD4+ cells, Tregs, and NK cells were the independent risk factors for CTCs. CTCs were associated with the decrease of immune surveillance in the peripheral blood in NSCLC patients. The decrease of immune surveillance contributed to the escape of CTCs from the killing effects of the immunocytes, as well as the formation of metastasized lesions in the target organs