Methyl-donor depletion of head and neck cancer cells in vitro establishes a less aggressive tumour cell phenotype

PURPOSE: DNA methylation plays a fundamental role in the epigenetic control of carcinogenesis and is, in part, influenced by the availability of methyl donors obtained from the diet. In this study, we developed an in-vitro model to investigate whether methyl donor depletion affects the phenotype and gene expression in head and neck squamous cell carcinoma (HNSCC) cells. METHODS: HNSCC cell lines (UD-SCC2 and UPCI-SCC72) were cultured in medium deficient in methionine, folate, and choline or methyl donor complete medium. Cell doubling-time, proliferation, migration, and apoptosis were analysed. The effects of methyl donor depletion on enzymes controlling DNA methylation and the pro-apoptotic factors death-associated protein kinase-1 (DAPK1) and p53 upregulated modulator of apoptosis (PUMA) were examined by quantitative-PCR or immunoblotting. RESULTS: HNSCC cells cultured in methyl donor deplete conditions showed significantly increased cell doubling times, reduced cell proliferation, impaired cell migration, and a dose-dependent increase in apoptosis when compared to cells cultured in complete medium. Methyl donor depletion significantly increased the gene expression of DNMT3a and TET-1, an effect that was reversed upon methyl donor repletion in UD-SCC2 cells. In addition, expression of DAPK1 and PUMA was increased in UD-SCC2 cells cultured in methyl donor deplete compared to complete medium, possibly explaining the observed increase in apoptosis in these cells. CONCLUSION: Taken together, these data show that depleting HNSCC cells of methyl donors reduces the growth and mobility of HNSCC cells, while increasing rates of apoptosis, suggesting that a methyl donor depleted diet may significantly affect the growth of established HNSCC

Is concern about young people's anti-social behaviour associated with poor health? cross-sectional evidence from residents of deprived urban neighbourhoods

<p><b>Background:</b> Young people in disadvantaged neighbourhoods are often the focus of concerns about anti-social behaviour (ASB). There is inconsistent evidence to support the hypothesis that perceptions of ASB (PASB) are associated with poor health. We ask whether perceptions of young people's ASB are associated with poor health; and whether health, demographic and (psycho)social characteristics can help explain why PASB varies within disadvantaged neighbourhoods (Glasgow, UK).</p> <p><b>Methods:</b> Regression analysis of survey data exploring associations between perceiving teenagers hanging around to be a serious neighbourhood problem and SF-12v2 mental and physical health scores (higher = better), including adjustment for demographic characteristics. Further analysis explored associations with self-reported measures of health service use, psychosocial characteristics of homes and neighbourhoods and social contacts.</p> <p><b>Results:</b> 6008 adults participated (50% response) and 22% (n = 1,332) said teenagers were a serious neighbourhood problem (the most frequently reported local problem). Demographic characteristics associated with perceiving serious teenager problems included regular health service use, age (inverse relationship), financial problems and living with children. Lower SF-12v2 physical health scores were associated with perceiving teenager problems after adjustment for demographic variables (OR 0.98; 95%CI 0.97,0.99; p = < 0.001), whilst adjusted findings for mental health scores were less conclusive (OR 0.99; 95%CI 0.98,1.00; p = 0.103). Further analysis suggested that perceiving teenager problems was more strongly associated with a number of self-reported psychosocial factors: e.g. lacking social support, < weekly family contacts, poor neighbourhood safety, low trust in neighbours, neighbourhood perceived to be a barrier to self-esteem, and neighbourhood decline.</p> <p><b>Conclusions:</b> Given the evidence we found of weak and small associations between PASB and health, we caution against assuming that tackling concern about teenagers' ASB will lead to substantial public health gains in disadvantaged areas. Although the findings do not present a compelling case for making PASB a public health priority, it is still important to address concerns about young people's ASB. Reasons for doing so may include improving social cohesion, reducing fear and isolation, and improving the general quality of people's lives - particularly in neighbourhoods burdened by multiple disadvantages. Future research should evaluate interventions that attempt to reduce PASB in disadvantaged areas. Findings from this study could help inform the targeting of such interventions.</p&gt

Domestic burglary drop and the security hypothesis

This study examines the role of household security devices in producing the domestic burglary falls in England and Wales. It extends the study of the security hypothesis as an explanation for the 'crime drop'. Crime Survey for England and Wales data are analysed from 1992 to 2011/12 via a series of data signatures indicating the nature of, and change in, the relationship between security devices and burglary. The causal role of improved security is strongly indicated by a set of interlocking data signatures: rapid increases in the prevalence of security, particularly in the availability of combinations of the most effective devices (door and window locks plus security lighting); a steep decline in the pro-portion of households without security accompanied by disproportionate rises in their burglary risk; and the decline being solely in forced rather than unforced entries to households. The study concludes that there is strong evidence that security caused the decline in burglary in England and Wales in the 1990s. Testing the security hypothesis across a wider range of crime types, countries and forms of security than examined to date, is required both to understand the crime drop and to derive lessons for future crime prevention practice and policy