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排序方式: 共有64条查询结果,搜索用时 0 毫秒
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Samson Mani Katarzyna Szymańska Cyrille Cuenin David Zaridze Karen Balassiano Sheila CS Lima Elena Matos Alexander Daudt Sergio Koifman Victor Wunsch Filho Ana MB Menezes Maria Paula Curado Gilles Ferro Thomas Vaissière Bakary S Sylla Massimo Tommasino Luis Felipe Ribeiro Pinto Paolo Boffetta Pierre Hainaut Paul Brennan Zdenko Herceg 《Epigenetics》2012,7(3):270-277
Cancers of the upper aerodigestive tract (UADT) are common forms of malignancy associated with tobacco and alcohol exposures, although human papillomavirus and nutritional deficiency are also important risk factors. While somatically acquired DNA methylation changes have been associated with UADT cancers, what triggers these events and precise epigenetic targets are poorly understood. In this study, we applied quantitative profiling of DNA methylation states in a panel of cancer-associated genes to a case-control study of UADT cancers. Our analyses revealed a high frequency of aberrant hypermethylation of several genes, including MYOD1, CHRNA3 and MTHFR in UADT tumors, whereas CDKN2A was moderately hypermethylated. Among differentially methylated genes, we identified a new gene (the nicotinic acetycholine receptor gene) as target of aberrant hypermethylation in UADT cancers, suggesting that epigenetic deregulation of nicotinic acetycholine receptors in non-neuronal tissues may promote the development of UADT cancers. Importantly, we found that sex and age is strongly associated with the methylation states, whereas tobacco smoking and alcohol intake may also influence the methylation levels in specific genes. This study identifies aberrant DNA methylation patterns in UADT cancers and suggests a potential mechanism by which environmental factors may deregulate key cellular genes involved in tumor suppression and contribute to UADT cancers.Key words: DNA methylation, upper aerodigestive tract, cancer, risk factors, biomarkers 相似文献
33.
Vibeke Secher Dam Donna MB Boedtkjer Christian Aalkjaer Vladimir Matchkov 《Channels (Austin, Tex.)》2014,8(4):361-369
The presence of Ca2+-activated Cl– currents (ICl(Ca)) in vascular smooth muscle cells (VSMCs) is well established. ICl(Ca) are supposedly important for arterial contraction by linking changes in [Ca2+]i and membrane depolarization. Bestrophins and some members of the TMEM16 protein family were recently associated with ICl(Ca). Two distinct ICl(Ca) are characterized in VSMCs; the cGMP-dependent ICl(Ca) dependent upon bestrophin expression and the ‘classical’ Ca2+-activated Cl– current, which is bestrophin-independent. Interestingly, TMEM16A is essential for both the cGMP-dependent and the classical ICl(Ca). Furthermore, TMEM16A has a role in arterial contraction while bestrophins do not. TMEM16A’s role in the contractile response cannot be explained however only by a simple suppression of the depolarization by Cl– channels. It is suggested that TMEM16A expression modulates voltage-gated Ca2+ influx in a voltage-independent manner and recent studies also demonstrate a complex role of TMEM16A in modulating other membrane proteins. 相似文献
34.
J. O'Grady MB ChB MRCP. S. Warrington MB BChir MA MRCP. M.J. Moti S. Bunting BSc. R. Flower BSc PhD. A.S.E. Fowle MD MRCP. E.A. Higgs BSc MSc. S. Moncada MD PhD. 《Prostaglandins & other lipid mediators》1980,19(2):319-332
Prostacyclin infused intravenously in human volunteers induces ex vivo inhibition of platelet aggregation, tachycardia and hypotension. The inhibition of platelet aggregation is obtained with slightly lower doses than those which exhibit cardiovascular effects.The cardiovascular effects disappeared within a few minutes after discontinuing the infusion of prostacyclin but the platelet effects were longer lasting.Prostacyclin did not have any effect on platelet count, platelet factor 3, accelerated partial thromboplastin time, prothrombin time, euglobulin clot lysis time, fibrinogen degradation products, blood glucose concentration or urine sodium potassium ratio. 相似文献
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JS Agerholm O Andersen MB Almskou C Bendixen J Arnbjerg GP Aamand US Nielsen F Panitz AH Petersen 《Acta veterinaria Scandinavica》2004,45(3):133
To investigate the congenital complex vertebral malformation syndrome (CVM) in Holstein calves, two breeding studies were
performed including 262 and 363 cows, respectively. Cows were selected from the Danish Cattle Database based on pedigree and
insemination records. Selected cows were progeny of sires with an established heterozygous CVM genotype and pregnant after
insemination with semen from another sire with heterozygous CVM genotype. Following calving the breeders should state, if
the calf was normal and was requested to submit dead calves for necropsy. In both studies, significantly fewer CVM affected
calves than expected were obtained; a finding probably reflecting extensive intrauterine mortality in CVM affected foetuses.
The findings illustrate increased intrauterine mortality as a major potential bias in observational studies of inherited disorders. 相似文献
38.
Mascheretti S Rogatcheva MB Gündüz I Fredga K Searle JB 《Proceedings. Biological sciences / The Royal Society》2003,270(1524):1593-1599
There is a long-standing debate as to how Ireland attained its present fauna; we help to inform this debate with a molecular study of one species. A 1110 base pair fragment of the mitochondrial cytochrome b gene was sequenced in 74 specimens of the pygmy shrew, Sorex minutus, collected from throughout its western Palaearctic range. Phylogenetic analysis of these sequences revealed several well-supported lineages. Most of the 65 haplotypes belonged to a northern lineage, which ranged from Britain in the west to Lake Baikal in the east. The other lineages were largely limited to Iberia, Italy and the Balkans. One exception, however, was a lineage found in both Ireland and Andorra. This affinity, and the large difference between the mitochondrial sequences of Irish and British individuals, suggest that pygmy shrews did not colonize Ireland via a land connection from Britain, as has been previously supposed, but instead were introduced by boat from southwest continental Europe. All the Irish pygmy shrews analysed were identical or very similar in cytochrome b sequence, suggesting an extreme founding event. 相似文献
39.
Elevated ammonium concentrations in the medium of cultivated cells have
been shown to increase the intracellular levels of uridine-5'-diphospho-
N-acetylglucosamine (UDP-GlcNAc) and uridine-5'-diphospho-N-
acetylgalactosamine (UDP-GalNAc; Ryll et al., 1994). These sugar
nucleotides are substrates for glycosyltransferases in the glycosylation
pathway. In our experiments, recombinant Chinese hamster ovary cells
producing an immunoadhesin glycoprotein (GP1-IgG) have been cultivated
under controlled cell culture conditions in the presence of different
ammonium concentrations.15N-Labeled ammonium chloride (15NH4Cl) was added
exogenously to the cell culture media to determine if ammonium was
incorporated into UDP-GlcNAc and cytidine-5'-
monophospho-N-acetylneuraminic acid (CMP-NANA) pools, and subsequently
incorporated into GP1-IgG as N-linked glycans. The intracellular pools of
UDP-activated hexosamines (UDP-GNAc) were followed during the time course
of the experiment. To assess the extent of15NH4+incorporation into the
glycans of GP1-IgG, the glycoprotein was first purified to homogeneity by
protein A chromatography. Enzymatically released N- glycans were then
analyzed by matrix-assisted laser desorption/ionization time-of-flight mass
spectrometry. N-Glycans synthesized in the presence of15NH4Cl revealed an
N-glycan-dependent increase in mass-to-charge of 2.5-4.8 Da. These results
indicate that 60-70% of the total nitrogen containing monosaccharides had
incorporated15N. Presumably,15NH4+was incorporated into GlcNAc and N-
acetylneuraminic acid as proposed earlier (Ryll et al., 1994). This might
be a universal and previously not described reaction in mammalian cells
when exposed to nonphysiological but in cell culture commonly found
concentrations of ammonium. The data presented here are of significance for
glycoprotein production in mammalian cell culture, since it has been shown
previously that elevated levels of UDP- activated hexosamines affect
N-glycan characteristics such as branching and degree of amino sugar
incorporation. In addition, our results demonstrate that isotope labeling
in combination with MALDI-TOF-MS can be used as an alternate tool to
radioactive labeling of sugar substrates in metabolic studies.
相似文献
40.