KCa1.1, a calcium-activated potassium channel subunit alpha 1, is targeted by miR-17-5p and modulates cell migration in malignant pleural mesothelioma

© 2016 Lin et al. Background: Malignant pleural mesothelioma (MPM) is an aggressive, locally invasive, cancer elicited by asbestos exposure and almost invariably a fatal diagnosis. To date, we are one of the leading laboratory that compared microRNA expression profiles in MPM and normal mesothelium samples in order to identify dysregulated microRNAs with functional roles in mesothelioma. We interrogated a significant collection of MPM tumors and normal pleural samples in our biobank in search for novel therapeutic targets. Methods: Utilizing mRNA-microRNA correlations based on differential gene expression using Gene Set Enrichment Analysis (GSEA), we systematically combined publicly available gene expression datasets with our own MPM data in order to identify candidate targets for MPM therapy. Results: We identified enrichment of target binding sites for the miR-17 and miR-30 families in both MPM tumors and cell lines. RT-qPCR revealed that members of both families were significantly downregulated in MPM tumors and cell lines. Interestingly, lower expression of miR-17-5p (P = 0.022) and miR-20a-5p (P = 0.026) was clearly associated with epithelioid histology. We interrogated the predicted targets of these differentially expressed microRNA families in MPM cell lines, and identified KCa1.1, a calcium-activated potassium channel subunit alpha 1 encoded by the KCNMA1 gene, as a target of miR-17-5p. KCa1.1 was overexpressed in MPM cells compared to the (normal) mesothelial line MeT-5A, and was also upregulated in patient tumor samples compared to normal mesothelium. Transfection of MPM cells with a miR-17-5p mimic or KCNMA1-specific siRNAs reduced mRNA expression of KCa1.1 and inhibited MPM cell migration. Similarly, treatment with paxilline, a small molecule inhibitor of KCa1.1, resulted in suppression of MPM cell migration. Conclusion: These functional data implicating KCa1.1 in MPM cell migration support our integrative approach using MPM gene expression datasets to identify novel and potentially druggable targets

Drug use and nightlife: more than just dance music

<p>Abstract</p> <p>Background</p> <p>Research over the last decade has focused almost exclusively on the association between electronic music and MDMA (3,4-Methylenedioxymethamphetamine or "ecstasy") or other stimulant drug use in clubs. Less attention has been given to other nightlife venues and music preferences, such as rock music or southern/funky music. This study aims to examine a broader spectrum of nightlife, beyond dance music. It looks at whether certain factors influence the frequency of illegal drug and alcohol use: the frequency of going to certain nightlife venues in the previous month (such as, pubs, clubs or goa parties); listening to rock music, dance music or southern and funky music; or sampling venues (such as, clubs, dance events or rock festivals). The question of how these nightlife variables influence the use of popular drugs like alcohol, MDMA, cannabis, cocaine and amphetamines is addressed.</p> <p>Methods</p> <p>The study sample consisted of 775 visitors of dance events, clubs and rock festivals in Belgium. Study participants answered a survey on patterns of going out, music preferences and drug use. Odds ratios were used to determine whether the odds of being an illegal substance user are higher for certain nightlife-related variables. Furthermore, five separate ordinal regression analyses were used to investigate drug use in relation to music preference, venues visited during the last month and sampling venue.</p> <p>Results</p> <p>Respondents who used illegal drugs were 2.5 times more likely to report that they prefer dance music. Goa party visitors were nearly 5 times more likely to use illegal drugs. For those who reported visiting clubs, the odds of using illegal drugs were nearly 2 times higher. Having gone to a pub in the last month was associated with both more frequent alcohol use and more frequent illegal substance use. People who reported liking rock music and attendees of rock festivals used drugs less frequently.</p> <p>Conclusions</p> <p>It was concluded that a more extended recreational environment, beyond dance clubs, is associated with frequent drug use. This stresses the importance of targeted prevention in various recreational venues tailored to the specific needs of the setting and its visitors.</p

Drug use and nightlife: more than just dance music

<p>Abstract</p> <p>Background</p> <p>Research over the last decade has focused almost exclusively on the association between electronic music and MDMA (3,4-Methylenedioxymethamphetamine or "ecstasy") or other stimulant drug use in clubs. Less attention has been given to other nightlife venues and music preferences, such as rock music or southern/funky music. This study aims to examine a broader spectrum of nightlife, beyond dance music. It looks at whether certain factors influence the frequency of illegal drug and alcohol use: the frequency of going to certain nightlife venues in the previous month (such as, pubs, clubs or goa parties); listening to rock music, dance music or southern and funky music; or sampling venues (such as, clubs, dance events or rock festivals). The question of how these nightlife variables influence the use of popular drugs like alcohol, MDMA, cannabis, cocaine and amphetamines is addressed.</p> <p>Methods</p> <p>The study sample consisted of 775 visitors of dance events, clubs and rock festivals in Belgium. Study participants answered a survey on patterns of going out, music preferences and drug use. Odds ratios were used to determine whether the odds of being an illegal substance user are higher for certain nightlife-related variables. Furthermore, five separate ordinal regression analyses were used to investigate drug use in relation to music preference, venues visited during the last month and sampling venue.</p> <p>Results</p> <p>Respondents who used illegal drugs were 2.5 times more likely to report that they prefer dance music. Goa party visitors were nearly 5 times more likely to use illegal drugs. For those who reported visiting clubs, the odds of using illegal drugs were nearly 2 times higher. Having gone to a pub in the last month was associated with both more frequent alcohol use and more frequent illegal substance use. People who reported liking rock music and attendees of rock festivals used drugs less frequently.</p> <p>Conclusions</p> <p>It was concluded that a more extended recreational environment, beyond dance clubs, is associated with frequent drug use. This stresses the importance of targeted prevention in various recreational venues tailored to the specific needs of the setting and its visitors.</p

What factors are predictive of surgical resection and survival from localised nonsmall cell lung cancer?

© 2014, Australasian Medical Publishing Co. Ltd. All rights reserved. Objective: To investigate opportunities to reduce lung cancer mortality after diagnosis of localised non-small cell lung cancer (NSCLC) in New South Wales through surgical resection.Main outcome measures: Resection rates and lung cancer mortality.Design, patients and setting: In this cohort study, resection rates and lung cancer mortality risk were explored using multivariate logistic regression and competing risk regression, respectively. Data for 3040 patients were extracted from the NSW Central Cancer Registry for the diagnostic period 1 January 2003 to 31 December 2007. Subset analyses for patients at low surgical risk indicated resection rates and outcomes under ideal circumstances.Results: The resection rate in NSW was estimated to be between 38% and 43%, peaking at 59% by local health district (LHD) of residence. Not having a resection was associated with older age, lower socioeconomic status, lack of private health insurance, and residence by LHD. Adjusted 5-year cumulated probabilities of death were 76% in absence of resection, 30% for wedge resection, 18% for segmental resection, 22% for lobectomy and 45% for pneumonectomy. Of 255 “low surgical risk” patients, 71% had a resection. Those not receiving a resection had a higher probability of death (adjusted subhazard ratio, 14.1; 95% CI, 7.2–27.5). If the low overall resection rate of 38%–43% in NSW were increased to 59% (the highest LHD resection rate), the proportion of all patients with localised NSCLC dying of NSCLC in the 5 years from diagnosis would decrease by about 10%, based on differences in probabilities of death by resection estimated in this study.Conclusions: Potential exists to reduce deaths from NSCLC in NSW through increased resection