Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Keywords: carcinoma ; POPULATION ; GENE-EXPRESSION ; MARKER ; OVARIAN-CANCER ; PROSTATE-CANCER ; METAANALYSIS ; susceptibility loci ; GENOME-WIDE ASSOCIATION ; PLATFORM
    Abstract: Common variants in the hepatocyte nuclear factor 1 homeobox B (HNF1B) gene are associated with the risk of Type II diabetes and multiple cancers. Evidence to date indicates that cancer risk may be mediated via genetic or epigenetic effects on HNF1B gene expression. We previously found single-nucleotide polymorphisms (SNPs) at the HNF1B locus to be associated with endometrial cancer, and now report extensive fine-mapping and in silico and laboratory analyses of this locus. Analysis of 1184 genotyped and imputed SNPs in 6608 Caucasian cases and 37 925 controls, and 895 Asian cases and 1968 controls, revealed the best signal of association for SNP rs11263763 (P = 8.4 x 10(-14), odds ratio = 0.86, 95% confidence interval = 0.82-0.89), located within HNF1B intron 1. Haplotype analysis and conditional analyses provide no evidence of further independent endometrial cancer risk variants at this locus. SNP rs11263763 genotype was associated with HNF1B mRNA expression but not with HNF1B methylation in endometrial tumor samples from The Cancer Genome Atlas. Genetic analyses prioritized rs11263763 and four other SNPs in high-to-moderate linkage disequilibrium as the most likely causal SNPs. Three of these SNPs map to the extended HNF1B promoter based on chromatin marks extending from the minimal promoter region. Reporter assays demonstrated that this extended region reduces activity in combination with the minimal HNF1B promoter, and that the minor alleles of rs11263763 or rs8064454 are associated with decreased HNF1B promoter activity. Our findings provide evidence for a single signal associated with endometrial cancer risk at the HNF1B locus, and that risk is likely mediated via altered HNF1B gene expression.
    Type of Publication: Journal article published
    PubMed ID: 25378557
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] The most common human cancers are malignant neoplasms of the skin. Incidence of cutaneous melanoma is rising especially steeply, with minimal progress in non-surgical treatment of advanced disease. Despite significant effort to identify independent predictors of melanoma outcome, no ...
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    Electronic Resource
    Electronic Resource
    s.l. : American Chemical Society
    Biochemistry 15 (1976), S. 3187-3191 
    ISSN: 1520-4995
    Source: ACS Legacy Archives
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    Publication Date: 2018-08-17
    Description: Samantha J. Stehbens, Robert J. Ju, Mark N. Adams, Samuel R. Perry, Nikolas K. Haass, David M. Bryant, and Pamela M. Pollock Fibroblast growth factor receptors (FGFRs) are a family of receptor tyrosine kinases that control a diverse range of biological processes during development and in adult tissues. We recently reported that somatic FGFR2 mutations are associated with shorter survival in endometrial cancer. However, little is known about how these FGFR2 mutations contribute to endometrial cancer metastasis. Here, we report that expression of the activating mutations FGFR2 N550K and FGFR2 Y376C in an endometrial cancer cell model induce Golgi fragmentation, and loss of polarity and directional migration. In mutant FGFR2-expressing cells, this was associated with an inability to polarise intracellular pools of FGFR2 towards the front of migrating cells. Such polarization defects were exacerbated in three-dimensional culture, where FGFR2 mutant cells were unable to form well-organised acini, instead undergoing exogenous ligand-independent invasion. Our findings uncover collective cell polarity and invasion as common targets of disease-associated FGFR2 mutations that lead to poor outcome in endometrial cancer patients.
    Keywords: Cell Biology and Disease, Collective Cell Migration
    Print ISSN: 0021-9533
    Electronic ISSN: 1477-9137
    Topics: Biology , Medicine
    Published by Company of Biologists
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    Publication Date: 2018-03-15
    Description: Introduction Preventing and reducing violence against women (VAW) and maternal mortality are Sustainable Development Goals. Worldwide, the maternal mortality ratio has fallen about 44% in the last 25 years, and for one maternal death there are many women affected by severe acute maternal morbidity (SAMM) requiring management in the intensive care unit (ICU). These women represent the most critically ill obstetric patients of the maternal morbidity spectrum and should be studied to complement the review of maternal mortality. VAW has been associated with all-cause maternal deaths, and since many women (30%) endure violence usually exerted by their intimate partners and this abuse can be severe during pregnancy, it is important to determine whether it impacts SAMM. Thus, this study aims to investigate the impact of VAW on SAMM in the ICU. Methods and analysis This will be a prospective case-control study undertaken in a tertiary healthcare facility in Lima-Peru, with a sample size of 109 cases (obstetric patients admitted to the ICU) and 109 controls (obstetric patients not admitted to the ICU selected by systematic random sampling). Data on social determinants, medical and obstetric characteristics, VAW, pregnancy and neonatal outcome will be collected through interviews and by extracting information from the medical records using a pretested form. Main outcome will be VAW rate and neonatal mortality rate between cases and controls. VAW will be assessed by using the WHO instrument. Binary logistic followed by stepwise multivariate regression and goodness of fit test will assess any association between VAW and SAMM. Ethics and dissemination Ethical approval has been granted by the La Trobe University, Melbourne-Australia and the tertiary healthcare facility in Lima-Peru. This research follows the WHO ethical and safety recommendations for research on VAW. Findings will be presented at conferences and published in peer-reviewed journals.
    Keywords: Open access, Public health
    Electronic ISSN: 2044-6055
    Topics: Medicine
    Published by BMJ Publishing
    Signatur Availability
    BibTip Others were also interested in ...
  • 6
    Publication Date: 2018-04-07
    Description: Objective To determine the effect of age and gender on persistence and adherence in patients taking dabigatran for atrial fibrillation. Design A retrospective observational study over 4 years using refill prescription data from the National Pharmaceutical Database. Setting All patients in New Zealand who received dabigatran from July 2011 to September 2015. Population 43 339 people filled at least one prescription of dabigatran. Main outcome measures The proportion of patients with good adherence (treatment available at least 80% of the time), and the proportion at risk of thrombosis (a break in treatment of more than 2 days) measured 6-monthly for 3 years. Medication persistence recorded over 3 years. Results Persistence was highest in older patients and showed a significant correlation with age (p〈0.001); 24% over 70 years had discontinued treatment by 6 months compared with 50% under 50 years. Adherence was highest in the elderly (p〈0.001) with 90% of patients over 80 years with good adherence at 12 months compared with 70% in patients aged 50–60 years and less than 60% in those under 50 years. The time at risk of thrombosis showed a similar pattern with 25% below 60 years with inadequate anticoagulation more than 20% of the time. Adherence dropped during the first 18 months of treatment with the most marked fall in those under 50 years. Adherence shows that breaks in treatment are common with 30% of men under 60 years with a break in treatment of at least 28 days during the first 12 months. Conclusion Adherence and persistence correlate with the patient’s age. Those over 70 years have high adherence consistent over time whereas younger patients have significantly worse adherence which declines over the first 18 months, with the lowest rate in those under 50 years. Adherence in our study is lower than reported in clinical trials, therefore the benefit of dabigatran in stroke prevention may not be realised in clinical practice especially in younger patients.
    Keywords: Open access, Haematology (incl blood transfusion)
    Electronic ISSN: 2044-6055
    Topics: Medicine
    Published by BMJ Publishing
    Signatur Availability
    BibTip Others were also interested in ...
  • 7
    Publication Date: 2018-06-12
    Description: Journal of the American Chemical Society DOI: 10.1021/jacs.8b04455
    Print ISSN: 0002-7863
    Electronic ISSN: 1520-5126
    Topics: Chemistry and Pharmacology
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...