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Drug resistance remains a major challenge in epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy. Bcl-2-like protein 11 (BIM), a B-cell lymphoma 2 family pro-apoptotic protein, is a prime target for specific anti-cancer therapeutics. However, the epigenetic regulation of BIM in non-small cell lung cancer (NSCLC) cell lines and patients with NSCLC in association with EGFR-TKI resistance requires investigation. Methylation-specific PCR (MSP), pyrosequencing, and nested quantitative (q)-MSP were conducted to explore the methylation status of BIM in NSCLC cell lines. In addition, the methylation profile of BIM in patients with NSCLC was assessed by nested q-MSP using circulating free DNA. Cell lines, treated with methylation inhibitor 5-Aza-2'-deoxycytidine (AZA) or histone deacetylation inhibitor trichostatin A (TSA) prior to gefitinib treatment, were examined for BIM gene expression and resistance to gefitinib. All cell lines used in the present study presented with hypo-methylated BIM. Treatment with AZA had no effect on BIM RNA expression in PC9 cells or the gefitinib-resistant cell lines PC9/R and PC9/G2, nor did it reverse their resistance to gefitinib. In contrast, TSA treatment produced the opposite result. In the present study, 25 (78.1%) patients with hypo-methylated BIM and 7 patients (21.9%) with partial or hyper-methylated BIM were identified. The clinicopathological data revealed a random hypo-methylated BIM distribution amongst patients with NSCLC. In the overall study group and EGFR mutant group, hypo-methylated BIM carriers presented with no significant differences in progression free survival compared with patients with partial or hyper-methylated BIM. All cell lines in the present study and the majority of patients with NSCLC carried hypo-methylated BIM. Histone deacetylation, as opposed to promoter methylation, may contribute to the epigenetic silencing of BIM and lead to EGFR TKI resistance in NSCLC. [ABSTRACT FROM AUTHOR]

Background: POTEE (POTE ankyrin domain family, member E) is a newly identified cancer-testis antigen that has been found to be expressed in a wide variety of human cancers including cancers of the colon, prostate, lung, breast, ovary, and pancreas. Aim: To measure the serum levels of POTEE in patients with non-small-cell lung cancer (NSCLC) and to explore the clinical significance of POTEE in NSCLC. Patients and Methods: 104 NSCLC patients, 66 benign lung disease patients and 80 healthy volunteers were enrolled in this study from May 2013 to February 2014. Serum POTEE levels were measured using enzyme-linked immunosorbent assay (ELISA). Numerical variables were recorded as means ± standard deviation (SD) and analyzed by independent t tests. Categorical variables were calculated as rates and were analyzed using a χ2 test or Fisher’s exact test. Survival curves were estimated and compared using the Kaplan-Meier method and log-rank tests. Results: Serum POTEE levels were significantly higher in NSCLC patients than in benign lung disease patients and healthy controls (mean ± SD [pg/ml], 324.38± 13.84 vs. 156.93 ± 17.38 and 139.09 ± 15.80, P<0.001) and were significantly correlated with TNM stage. Survival analysis revealed that patients with low serum POTEE had longer progression-free survival (PFS) than those with high serum POTEE (P=0.021). Cox multivariate analysis indicated that POTEE was an independent prognostic factor of progression-free survival (P =0.009, hazard ratio, 2.440). Conclusions: Serum POTEE level in NSCLC patients is associated with TNM stage and is a potential prognostic factor. [ABSTRACT FROM AUTHOR]

Abstract: Recent studies demonstrate that progesterone (PROG) significantly reduces cerebral edema and enhances functional recovery from traumatic brain injury (TBI) and stroke in several animal models, but its concrete mechanism is still unknown. This study was designed to investigate the inhibitory effects of PROG on inflammatory response after stroke and its influence on the structure of blood-brain barrier (BBB). In the treatment group, PROG was dissolved in 22.5% 2-hydroxypropyl-bcyclodextrin and given in a dose of 8mg/kg by intraperitoneal injection 1h and 6h after permanent occlusion of middle cerebral artery (pMCAO). Additional injections of 15mg/kg were administered subcutaneously once a day after pMCAO. The expression of tumor necrosis factor-alpha (TNF-α), matrix metalloproteinase-9 (MMP-9) and claudin5 was measured by western blot technique. Evan''s blue extravasation and brain water content in the ipsilateral hemisphere was also detected to evaluate the permeability of BBB. Western blot analysis revealed that the expression of TNF-α and MMP-9 were reduced while claudin5 was up-regulated in brain tissues of PROG-treated rats. In addition, examination of BBB permeability also showed that administration of PROG significantly reduced Evan''s blue extravasation and brain water content in the ipsilateral hemisphere compared to vehicle-treated rats. Our findings reveal that PROG inhibited the inflammatory response after experimental stroke and mitigated the severity of brain damage, suggesting a role for PROG in the integrity of the BBB and subsequent edema formation following cerebral ischemia. [Copyright &y& Elsevier]

The acquired drug resistance would influence the efficacy of cisplatin-based chemotherapy in non-small-cell lung cancer. The present study aimed to investigate the correlation of long non-coding RNA (lncRNA) H19 with cisplatin-resistance and clinical outcome in lung adenocarcinoma. In our study, the expression of H19 in cisplatin-resistant A549/DDP cells was unregulated. Knockdown of H19 restored the response of A549/DDP cells to cisplatin. H19-mediated chemosensitivity enhancement was associated with metastasis, induction of G0/G1 cell-cycle arrest, cell proliferation, and increased apoptosis. Furthermore, lncRNA H19 expression was significantly related to TNM stage and metastasis (P = 0.012). Overexpression of H19 was negatively correlated with cisplatin-based chemotherapy response in patients. Patients with high H19 expression exhibited a significantly shorter median progression-free survival (PFS) [4.7 months] than the low-expression patients (6.3months) [P = 0.002]. In summary, H19-mediated regulation of cisplatin resistance in human lung adenocarcinoma cells is demonstrated for the first time. H19 could potentially serve as a molecular marker to predict the clinical outcomes of lung adenocarcinoma patients.

Objective: To investigate the etiology of severe hand-foot-mouth disease (HFMD) in children in Henan province., Methods: A total of 244 HFMD cases admitted to a hospital in Zhengzhou from April to June of 2014 were recruited for research sampling, Real-time RT-PCR, virus isolation, VP1 sequencing and alignment methods were used to test the enterovirus-related etiology. SPSS 17.0 was used in performing statistical analysis., Results: There were 109 severe and 135 mild cases among all the 244 HFMD cases. The number of enterovirus positive stool samples was 229, with positive rate as 93.85%. EV71, Cox A16 and Cox A10 made up 83.84%, 5.68% and 8.30% of the enterovirus etiologicy, strains, respectively. EV71 infection caused 8 HFMD cases with heart-lung failure and 2 death, Cox A10 infection led to 1 HFMD case with heart-lung failure and death. There were statistically differences seen regarding the enterovirus infection rates between severe and the mild HFMD cases (χ(2)=5.312,P=0.021). Statistically significant difference was seen in the constituent ratio of EV71, Cox A16 and the others by Fisher' s exact test (P=0.048). There was statistically significant difference seen between the cardiorespiratory failure rate and the fatality rate by EV71 and Cox A10 infection (χ(2)=0.051,P=0.821; χ(2)=2.198,P=0.138). Cox A10 strains idenfied in Henan in 2014 belonged to genotype 6. The rates on homology of nucleotide and amino acid among the Cox A10 strains in Henan in 2014 were 94.3%-99.7% and 96.3%-100.0% respectively., Conclusions: EV71 still remained the most common pathogen that causing severe HFMD in children, with the increasing Cox A10 percentage in the pathogens spectrum of HFMD infection. Cox A10 strains in Henan in 2014 belonged to genotype 6. Genotype 6 Cox A10 had appeared and widely distributed in Henan for long time, but not yet variated or reconstructed. Cox A10 infection could lead to cardio-respiratory failure thus called for the monitoring program on non-EV71 and non-Cox A16 enterovirus, especially Cox A10 to be strenthened.

Background: Epithelial-mesenchymal transition (EMT) is of great importance in tumor metastasis. Our previous study demonstrates that epithelial phenotype is related to epidermal growth factor receptor (EGFR) mutation and the sensitivity of EGFR tyrosine kinase inhibitors (TKIs) in advanced non-small cell lung cancer (NSCLC) patients. However, the role of EMT phenotype in malignant pleural effusions in predicting prognosis is unknown in lung adenocarcinoma patients., Method: Pleural effusions of lung adenocarcinoma patients were collected and made into cell block (CB). EGFR mutation was detected using amplification refractory mutation system (ARMS) PCR method and H-score system was applied to evaluate the staining intensity of EMT marker and tumor cell ratio., Results: Forty-three CB samples, including 22 samples before any treatment (baseline, group 1) and 21 with disease progression (group 2) after first-line chemotherapy, were enrolled in this study. The expression of N-cadherin and vimentin were low in the CB tumor cells. There was no significant difference in the tumor cell radio and E-cadherin expression in the two groups. E-cadherin expression had no association with sex, age and smoking status and also patient response in both the two groups. However, high E-cadherin expression was related to EGFR mutation (P=0.032) and long progression-free survival (PFS) (P=0.015) in group 1 but not group 2 samples., Conclusion: E-cadherin expression in CB samples was associated with EGFR mutation status and patient prognosis in lung adenocarcinoma patients in first-line chemotherapy.