CHRNA5 rs16969968 polymorphism is associated with lung cancer risk: A meta-analysis.

OBJECTIVE: To evaluate the genetic association between rs16969968 and lung cancer risk by meta-analysis. DATA SOURCE: We searched eligible studies from MEDLINE, Web of Science and EMBASE up to Dec, 2017. STUDY SELECTION: Association studies concerning rs16969968 and lung cancer risk were included. We assessed the association strength between this polymorphism and risk of lung cancer by calculating odds ratios (OR) and 95% confidence interval (95%CI). RESULTS: A total of 26 data sets comprising 30 772 lung cancers and 90 954 controls were included. rs16969968 was found to be associated with lung cancer risk in population of European ancestry in all models (A vs. G: OR = 1.30, 95%CI 1.27-1.33, P < 0.001; AA + GA vs. GG: OR = 1.38, 95%CI 1.33-1.43, P < 0.001; AA vs. GG + GA: OR = 1.45, 95%CI 1.38-1.53, P < 0.001), consistent with previous genome-wide association study (GWAS). However, no association was observed in Asians (A vs. G: OR = 1.19. 95%CI 0.95-1.49, P = 0.131). The minor allele A may increase the risk of lung cancer in both smokers (OR = 1.33, 95%CI 1.29-1.39, P < 0.001) and nonsmokers (OR = 1.25, 95%CI 1.12-1.39, P < 0.001). There was no obvious publication bias in all analyses. CONCLUSIONS: Our analysis provided more evidence that rs16969968 is a susceptibility locus of lung cancer in the Caucasians and that it may be not associated with the risk in the Asians.

Significance of cancer-associated fibroblasts in the regulation of gene expression in the leading cells of invasive lung cancer.

PURPOSE: Cancer-associated fibroblasts (CAFs) contribute to tumor progression through multiple pathways. However, the effect of CAFs on gene expression in lung cancer has been largely unknown. Here we systematically compared the gene expression changes in lung cancer cells induced by normal fibroblasts and CAFs. METHODS: Wound healing and cell proliferation assays were used to identify the property of CAFs used in this study. We used cDNA microarray analysis to compare gene expression in lung cancer cells cultured with either conditioned medium (CM) from lung CAFs or normal lung fibroblasts, the result of which was confirmed by RT-PCR and Western blot analysis. Immunohistochemistry on tissue sections from lung cancers was conducted to further confirm the results of cDNA microarray analysis. RESULTS: The expression of many genes was upregulated in cancer cells by CAF CM, particularly cell adhesion molecules, integrins, and anti-apoptotic protein Bcl-2. Expression of integrins appeared to be upstream from Bcl-2. We identified transforming growth factor-ß as a candidate factor that induced the expression of those genes in cancer cells. Immunohistochemical studies of clinical lung cancer tissues revealed that integrins and Bcl-2 were more highly expressed in the leading cells (LCs) than in the following cells, at the invasive front of cancer nests, which are adjacent to or in proximity to the stroma. Furthermore, the expression of integrins and Bcl-2 in LCs had a tendency to correlate with the clinical stage of cancer progression, including lymph node metastasis. CONCLUSIONS: Our results suggest that CAFs promote lung cancer progression partly through the direct regulation of gene expression in the LCs of invasive cancer nests.

[The relationship between the TSLC1 silencing and DNA methylation in human lung cancer cells].

BACKGROUND AND OBJECTIVE: The expression of TSLC1 is downregulated or abrogated in many kinds of tumors, and its downregulation is highly associated with DNA hypermethlyation. The aim of this study is to explore the relationship between TSLC1 silencing and DNA methylation of its promoter region in lung cancer cells. METHODS: We detected the expression pattern of TSLC1 in human normal lung tissue and three lung cancer cell lines (A549, NCI-H446 and Calu-3) by semi-quantitative RT-PCR and Real-time PCR. Then we detected the status of DNA methylation in TSLC1 promoter region with bisulfite sequencing in above normal lung tissue and lung cancer cell lines. After treatment of above cell lines with the inhibitor of DNA methyltransferase 5-Aza-2-deoxycytidine (5-Aza-dC), we detected the expression change of TSLC1 by Real-time PCR before and after the treatment of 5-Aza-dC. RESULTS: There was no methylation in TSLC1 promoter region in normal lung tissue and A549 cell line in which TSLC1 expressed; while there was DNA hypermethylation in TSLC1 promoter region in NCI-H446 and Calu-3 cell lines in which TSLC1 was abrogated, also the expression of TSLC1 in NCI-H446 and Calu-3 cell lines could be restored after treatment of 5-Aza-dC. CONCLUSION: The silencing of TSLC1 in lung cancer cells is due to the hypermethylation of its promoter region.

[The effect of montelukast, a leukotriene antagonist, on improvement of exercise-induced bronchoconstriction].

OBJECTIVE: To study the efficacy of montelukast, a cysteinyl leukotriene receptor antagonist, in the treatment and prevention of exercise-induced bronchoconstriction (EIB) in mild asthmatic patients and patients with exercise-induced asthma (EIA). METHODS: Thirty mild asthmatic patients with positive standardized exercise challenge test were enrolled. The subjects received montelukast 10 mg once daily in the evening. Standard exercise challenge was performed before, three days and twenty-eight days after the administration of the drug. The end points included: (1) Area under the percent fall in forced expiratory volume in one second (FEV1) versus time curve (AUC0 to approximately 60 min); (2) Time of recovery to within 5% of the pre-exercise baseline FEV1 value; and (3) Maximal percent fall in FEV1 from pre-exercise baseline. RESULTS: Montelukast caused significant reduction in AUC0 to approximately 60 min, which was (39 +/- 21)%.min before treatment as compared to (13 +/- 14)%.min and (12 +/- 14)%.min three days and twenty-eight days respectively after the treatment with montelukast. Time of recovery to within 5% of the pre-exercise baseline FEV1 value were (51 +/- 36) min, (26 +/- 28) min and (25 +/- 33) min respectively. The mean maximal percentage decrease in FEV1 after exercise was 44.4% before treatment, 26.8% and 18.2% following montelukast. FEV1 and peak expiratory flow rate (PEFR) were maintained to nearly normal during all the study. Inhale corticosteroid did not prevent EIB/EIA. CONCLUSION: Montelukast attenuates and protects against EIB/EIA.

Deep cerebral venous thrombosis in adults.

OBJECTIVE: To investigate the pathogenesis, clinical features, radiographic findings and therapeutic outcomes of non-acute intracranial deep venous thrombosis in adults. METHODS: Five patients who presented with increased intracranial pressure were examined with computed tomography, magnetic resonance and angiography, diagnosed as having non-acute intracranial deep venous thrombosis, and treated with thrombolytic therapy. They were reviewed retrospectively. RESULTS: There were 3 men and 2 women, aged from 22 to 49 years. Symptom duration ranged from 1 month to 7 months, and 4 of the 5 patients were associated with venous sinus thrombosis. Two patients developed cold and fever before the onset of disease, and 3 patients had no evident predisposing factors. After the infusion of thrombolytic and systemic anti-coagulant therapy, the neurological symptoms and signs of the patients were alleviated. CONCLUSIONS: Digital subtraction angiography (DSA) is more sensitive and accurate than MRI on diagnosing intracranial deep venous thrombosis. It may play an important role in the assessment of the treatment of intracranial deep venous thrombosis. Thrombolysis and anticoagulation of intracranial deep venous thrombosis appears to be a safe and efficacious treatment not only in the acute stage but also in the non-acute stage.