28 research outputs found
A population-based cohort study on sun habits and endometrial cancer
Background:No large cohort study has examined the risk of endometrial cancer in relation to sun exposure.Methods:A population-based cohort study of 29 508 women who answered a questionnaire in 1990-92, of whom 24 098 responded to a follow-up enquiry in 2000-02. They were followed for an average of 15.5 years.Results:Among the 17 822 postmenopausal women included, 166 cases of endometrial cancer were diagnosed. We used a multivariate Cox regression analysis adjusting for age and other selected demographic variables to determine the risk of endometrial cancer. Women using sun beds >3 times per year reduced their hazard risk (HR) by 40% (0.6, 95% confidence interval (CI) 0.4-0.9) or by 50% when adjusting for body mass index or physical activity (HR 0.5, 95% CI 0.3-0.9), and those women who were sunbathing during summer reduced their risk by 20% (HR 0.8 95% CI 0.5-1.5) compared with women who did not expose themselves to the sun or to artificial sun (i.e., sun beds).Conclusion:Exposure to artificial sun by the use of sun beds >3 times per year was associated with a 40% reduction in the risk of endometrial cancer, probably by improving the vitamin D levels during winter.British Journal of Cancer advance online publication, 23 June 2009; doi:10.1038/sj.bjc.6605149 www.bjcancer.com
Mesenchymal stromal cells inhibit NLRP3 inflammasome activation in a model of Coxsackievirus B3-induced inflammatory cardiomyopathy
Inflammation in myocarditis induces cardiac injury and triggers disease
progression to heart failure. NLRP3 inflammasome activation is a newly
identified amplifying step in the pathogenesis of myocarditis. We previously
have demonstrated that mesenchymal stromal cells (MSC) are cardioprotective in
Coxsackievirus B3 (CVB3)-induced myocarditis. In this study, MSC markedly
inhibited left ventricular (LV) NOD2, NLRP3, ASC, caspase-1, IL-1β, and IL-18
mRNA expression in CVB3-infected mice. ASC protein expression, essential for
NLRP3 inflammasome assembly, increased upon CVB3 infection and was abrogated
in MSC-treated mice. Concomitantly, CVB3 infection in vitro induced NOD2
expression, NLRP3 inflammasome activation and IL-1β secretion in HL-1 cells,
which was abolished after MSC supplementation. The inhibitory effect of MSC on
NLRP3 inflammasome activity in HL-1 cells was partly mediated via secretion of
the anti-oxidative protein stanniocalcin-1. Furthermore, MSC application in
CVB3-infected mice reduced the percentage of NOD2-, ASC-, p10- and/or IL-1β-
positive splenic macrophages, natural killer cells, and dendritic cells. The
suppressive effect of MSC on inflammasome activation was associated with
normalized expression of prominent regulators of myocardial contractility and
fibrosis to levels comparable to control mice. In conclusion, MSC treatment in
myocarditis could be a promising strategy limiting the adverse consequences of
cardiac and systemic NLRP3 inflammasome activation
Gene expression profiling during the transition to failure in TNF-a over-expressing mice demonstrates the development of autoimmune myocarditis.
Transgenic mice with cardiac-specific over-expression of tumor necrosis factor-a (TNF1.6) progress to dilated heart failure. A significant
inflammatory response precedes functional deterioration, and may contribute to cardiac damage in this model. To evaluate the underlying
molecular mechanisms, we assessed the gene expression in six groups of mouse hearts defined by age, gender, and phenotype (n = 3/group)
using Affymetrix microarray analysis. Phenotype was defined as compensated (in young TNF1.6) or decompensated (in older TNF1.6) via
echocardiogram. Of the >1000 transcripts altered in the compensated hearts (fold change > 2, P < 0.05 vs. wild-type (WT)), 102 were
identified as immune response genes, 20 of which function in antigen presentation and processing. When comparing the compensated and
decompensated hearts, >50 genes were differentially regulated, including seven immunoglobulin genes. Real-time reverse transcriptasepolymerase
chain reaction and cDNA microarray confirmed the Affymetrix data. Mac3+ macrophages, CD4+ T and CD45/B220+ B-cells
were identified in both compensated and decompensated hearts. However, a large amount of IgG was found deposited in areas devoid of
B-lymphocytes in the myocardium of decompensated TNF1.6 mice; no such accumulation was seen in the compensated or age-matched
controls. Furthermore, nuclei density analyses showed a two-fold increase in the myocardium of both compensated and decompensated
TNF1.6 mice (vs. WT). This study suggests that TNF-a over-expression activates not only the inflammatory response, but also humoral
immune responses within the transgenic hearts. The autoimmune response occurs concomitantly with cardiac decompensation and may
participate in triggering the transition to failure in TNF1.6 mice
Circulating sex hormones and breast cancer risk factors in postmenopausal women: reanalysis of 13 studies.
BACKGROUND: Breast cancer risk for postmenopausal women is positively associated with circulating concentrations of oestrogens and androgens, but the determinants of these hormones are not well understood.
METHODS: Cross-sectional analyses of breast cancer risk factors and circulating hormone concentrations in more than 6000 postmenopausal women controls in 13 prospective studies.
RESULTS: Concentrations of all hormones were lower in older than younger women, with the largest difference for dehydroepiandrosterone sulphate (DHEAS), whereas sex hormone-binding globulin (SHBG) was higher in the older women. Androgens were lower in women with bilateral ovariectomy than in naturally postmenopausal women, with the largest difference for free testosterone. All hormones were higher in obese than lean women, with the largest difference for free oestradiol, whereas SHBG was lower in obese women. Smokers of 15+ cigarettes per day had higher levels of all hormones than non-smokers, with the largest difference for testosterone. Drinkers of 20+ g alcohol per day had higher levels of all hormones, but lower SHBG, than non-drinkers, with the largest difference for DHEAS. Hormone concentrations were not strongly related to age at menarche, parity, age at first full-term pregnancy or family history of breast cancer.
CONCLUSION: Sex hormone concentrations were strongly associated with several established or suspected risk factors for breast cancer, and may mediate the effects of these factors on breast cancer risk