481 research outputs found

    RAD51 Is a Selective DNA Repair Target to Radiosensitize Glioma Stem Cells.

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    Patients with glioblastoma die from local relapse despite surgery and high-dose radiotherapy. Resistance to radiotherapy is thought to be due to efficient DNA double-strand break (DSB) repair in stem-like cells able to survive DNA damage and repopulate the tumor. We used clinical samples and patient-derived glioblastoma stem cells (GSCs) to confirm that the DSB repair protein RAD51 is highly expressed in GSCs, which are reliant on RAD51-dependent DSB repair after radiation. RAD51 expression and RAD51 foci numbers fall when these cells move toward astrocytic differentiation. In GSCs, the small-molecule RAD51 inhibitors RI-1 and B02 prevent RAD51 focus formation, reduce DNA DSB repair, and cause significant radiosensitization. We further demonstrate that treatment with these agents combined with radiation promotes loss of stem cells defined by SOX2 expression. This indicates that RAD51-dependent repair represents an effective and specific target in GSCs

    Elucidating drivers of oral epithelial dysplasia formation and malignant transformation to cancer using RNAseq

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    Oral squamous cell carcinoma (OSCC) is a prevalent cancer with poor prognosis. Most OSCC progresses via a non-malignant stage called dysplasia. Effective treatment of dysplasia prior to potential malignant transformation is an unmet clinical need. To identify markers of early disease, we performed RNA sequencing of 19 matched HPV negative patient trios: normal oral mucosa, dysplasia and associated OSCC. We performed differential gene expression, principal component and correlated gene network analysis using these data. We found differences in the immune cell signatures present at different disease stages and were able to distinguish early events in pathogenesis, such as upregulation of many HOX genes, from later events, such as down-regulation of adherens junctions. We herein highlight novel coding and non-coding candidates for involvement in oral dysplasia development and malignant transformation, and speculate on how our findings may guide further translational research into the treatment of oral dysplasia

    Is a combination of varenicline and nicotine patch more effective in helping smokers quit than varenicline alone? A randomised controlled trial

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    This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

    Characteristics of smokers who have never tried to quit: evidence from the British Opinions and Lifestyle Survey

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    Background An understanding of the characteristics of smokers who have never tried to quit may be useful to help identify and target these individuals and encourage them to attempt to give up smoking. Using national survey data we investigated variables associated with smokers reporting never having tried to quit. Methods Using data from the 2007 and 2009 UK Office for National Statistics Opinions and Lifestyle Survey we identified all self-reported current smokers aged 16+. The primary outcome was response to the question ‘have you ever tried to quit smoking?’ Univariable and multivariable logistic regression quantified the association between this outcome and several potential explanatory variables, including age, sex, socioeconomic status, health status, smoking behaviour, and knowledge of the dangers of smoking. Results Desire to quit was the most significant independent predictor of whether a smoker reported never having tried to quit. Smokers who reported that their health was good or very good were more likely to report never having tried to quit than those whose health was fair, bad or very bad (OR 1.59, 95% CI 1.05-2.41). Smokers who reported that no family members, friends or colleagues had been trying to get them to quit smoking in the last year were more likely to report never having tried to quit than those who reported that someone was trying to persuade them (OR 1.57, 95% CI 1.09-2.28). Smokers who hadn’t received any cessation advice from a health professional in the last five years which they considered to be helpful were also more likely to report never having tried to quit. Conclusions Smokers who do not want to quit, who are in good health, whose friends and family are not trying to get them to quit, and who do not report receiving helpful advice to quit from a health professional, are more likely to report never having tried to quit

    Systematic review and meta-analysis of opioid antagonists for smoking cessation

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    Objectives: This meta-analysis sought to evaluate the efficacy of opioid antagonists in promoting long-term smoking cessation. Post-treatment abstinence was examined as a secondary outcome and effects on withdrawal symptoms, craving and reduced consumption were also explored. Design: The search strategy for this meta-analysis included clinical trials (published and unpublished data) in the Cochrane Tobacco Addiction Group Specialized Register and MEDLINE. Participants: Adult smokers. Interventions: We included randomised trials comparing opioid antagonists to placebo or an alternative therapy for smoking cessation and reported data on abstinence for a minimum of 6 months. Primary and secondary outcome measures: Outcomes included smoking abstinence at long-term follow-up (primary); abstinence at end of treatment (secondary); and effects on withdrawal, craving and smoking consumption (exploratory). Results: 8 trials with a total of 1213 participants were included. Half the trials examined the benefit of adding naltrexone versus placebo to nicotine replacement therapy (NRT). There was no significant difference between naltrexone and placebo alone (relative risk (RR) 1.00; 95% CI 0.66 to 1.51) or as an adjunct to NRT (RR 0.95; 95% CI 0.70 to 1.30), with an overall pooled estimate of RR 0.97; 95% CI 0.76 to 1.24. Findings for naltrexone effects on withdrawal, craving and reduced smoking were equivocal. Conclusions: The findings indicate no beneficial effect of naltrexone alone or as an adjunct to NRT on short-term or long-term smoking abstinence. While further trials may narrow the confidence limits, they are unlikely to appreciably alter the conclusion

    Potential sources of cessation support for high smoking prevalence groups: a qualitative study

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    Objective: This study aimed to: i) explore potential sources of cessation support as nominated by disadvantaged smokers; and ii) identify factors influencing decisions to use these sources. Methods: Semi-structured interviews were conducted with 84 smokers accessing community service organisations from the alcohol and other drugs, homeless, and mental health sectors. Transcripts were coded and thematically analysed. Results: Doctors emerged as the most commonly recognised source of cessation support, followed by Quitline, community service organisation staff; and online resources. The main factors contributing to the possible use of these sources of support were identified as awareness, perceived usefulness and anticipated emotional support. Conclusions: The results suggest that doctors are an important group to consider when developing cessation interventions for disadvantaged smokers due to their recognised ability to provide practical and emotional support. However, efforts are needed to ensure doctors are aware of the benefits of cessation for these groups. Community service organisations appear to be another potentially effective source of cessation support for disadvantaged smokers. Implications for public health The results indicate that cessation interventions among high-priority groups should endeavour to provide personalised emotional and practical support. Doctors and community service organisation staff appear to be well-placed to deliver this support

    Tobacco prevention policies in west-African countries and their effects on smoking prevalence

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    Background: The WHO Framework Convention on Tobacco Control was shown to effectively lower smoking prevalence in in high income countries, however knowledge for low and middle income settings is sparse. The objective of this study was to describe WHO MPOWER policy measures in thirteen West-African countries and to investigate their correlation with smoking prevalence. Methods: Age-standardized smoking prevalence data and policy measures were collected from various WHO reports. For analysis MPOWER measures from 2008 and 2010, were combined with prevalence data from 2009 and 2011. Multiple linear regression models were set up. Results: In West-Africa mean smoking prevalence was approximately 20 % among males and approximately 3 % among females. Policy measures were mostly at a middle or low level. Regression analysis showed that tobacco cessation programs, health warnings on cigarettes, and higher price of cigarettes were negatively correlated with smoking prevalence. Significant effects were observed for only one policy measure (tobacco cessation programs) and only within the male population where smoking prevalence is generally higher. Conclusions: Tobacco control policies are enforced at relatively low levels in West-African countries. However, improving tobacco control policy implementation according to the WHO Framework Convention on Tobacco Control should assist in the reduction of smoking prevalence in African countries, thereby counteracting pro-smoking initiatives set forth by the tobacco industry

    Gestational weight gain and group prenatal care: A systematic review and meta-analysis

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    Abstract Background Group visits for chronic medical conditions in non-pregnant populations have demonstrated successful outcomes including greater weight loss compared to individual visits for weight management. It is plausible that group prenatal care can similarly assist women in meeting gestational weight gain goals. The purpose of this study was to evaluate the effect of group vs. traditional prenatal care on gestational weight gain. Methods A keyword search of Medline, Embase, Scopus, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, clinicaltrials.gov, and Google Scholar was performed up to April 2017. Studies were included if they compared gestational weight gain in a group prenatal care setting to traditional prenatal care in either randomized controlled trials, cohort, or case-control studies. The primary and secondary outcomes were excessive and adequate gestational weight gain according to the Institute of Medicine guidelines. Heterogeneity was assessed with the Q test and I2 statistic. Pooled relative risks (RRs) and confidence intervals (CI) were reported with random-effects models from the randomized controlled trials (RCT) and cohort studies. Results One RCT, one secondary analysis of an RCT, one study with “random assignment”, and twelve cohort studies met the inclusion criteria for a total of 13,779 subjects. Thirteen studies used the CenteringPregnancy model, defined by 10 sessions that emphasize goal setting and self-monitoring. Studies targeted specific populations such as adolescents, African-Americans, Hispanics, active-duty military or their spouses, and women with obesity or gestational diabetes. There were no significant differences in excessive [7 studies: pooled rates 47% (1806/3582) vs. 43% (3839/8521), RR 1.09, 95% CI 0.97–1.23] or adequate gestational weight gain [6 studies: pooled rates 31% (798/2875) vs. 30% (1410/5187), RR 0.92, 95% CI 0.79–1.08] in group and traditional prenatal care among the nine studies that reported categorical gestational weight gain outcomes in the meta-analysis. Conclusions Group prenatal care was not associated with excessive or adequate gestational weight gain in the meta-analysis. Since outcomes were overall inconsistent, we propose that prenatal care models (e.g., group vs. traditional) should be evaluated in a more rigorous fashion with respect to gestational weight gain
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