1,721,041 research outputs found
Treatment of prostate cancer cells with S-adenosylmethionine leads to genome-wide alterations in transcription profiles
No full textThe hypomethylation of DNA may support tumor progression; however, the mechanism underlying this relationship is not clear. Several studies have demonstrated that the in vitro application of the methyl donor S-adenosylmethionine (SAM) leads to promoter remethylation and the downregulation of proto-oncogene expression in cancer cells. It is not clear if this represents a general mechanism of SAM or is limited to selected genes. We examined this problem using new bisulfite sequencing and transcriptomic technologies. Treatment with SAM caused the downregulation of proliferation, migration, and invasion of prostate cancer (PC-3) cells. RNA sequencing revealed the genome-wide downregulation of genes involved in proliferation, migration, invasion, and angiogenesis. Real-time PCR of a subset of the genes confirmed these results. Reduced representation bisulfite sequencing (RRBS) displayed only minor differential methylation between treated cells and controls. In summary, we confirmed the anti-proliferative and anti-invasive effects of SAM. Additionally, we observed anti-migratory effects and downregulation of genes, especially those related to cancerogenesis. For some of the related genes, this is the first reported evidence of an association with prostate cancer. However, genome-wide modifications in methylation profiles were not observed by RRBS; thus, they are obviously not a major cause of alteration in transcription profiles and anti-cancer effects. (C) 2016 Elsevier B.V. All rights reserved
The Cannabinoid CB1/CB2 Agonist WIN55212.2 Promotes Oligodendrocyte Differentiation In Vitro and Neuroprotection During the Cuprizone-Induced Central Nervous System Demyelination
No full textAim and methodsDifferent types of insults to the CNS lead to axon demyelination. Remyelination occurs when the CNS attempts to recover from myelin loss and requires the activation of oligodendrocyte precursor cells. With the rationale that CB1 receptor is expressed in oligodendrocytes and marijuana consumption alters CNS myelination, we study the effects of the cannabinoid agonist WIN55212.2 in (1) an invitro model of oligodendrocyte differentiation and (2) the cuprizone model for demyelination. ResultsThe synthetic cannabinoid agonist WIN55212.2 at 1M increased the myelin basic protein mRNA and protein expression invitro. During cuprizone-induced acute demyelination, the administration of 0.5mg/kg WIN55212.2 confers more myelinated axons, increased the expression of retinoid X receptor alpha, and declined nogo receptor expression. Controversially, 1mg/kg of the drug increased the number of demyelinated axons and reduced the expression of nerve growth factor inducible, calreticulin and myelin-related genes coupling specifically with a decrease in 2,3-cyclic nucleotide 3 phosphodiesterase expression. ConclusionThe cannabinoid agonist WIN55212.2 promotes oligodendrocyte differentiation invitro. Moreover, 0.5mg/kg of the drug confers neuroprotection during cuprizone-induced demyelination, while 1mg/kg aggravates the demyelination process.DFG CNMPB [CNMPB C1-6]; Northern German Addiction Research Federatio
Influence of total genomic alteration and chromosomal fragmentation on response to a combination of azacitidine and lenalidomide in a cohort of patients with very high risk MDS
No full textWe genetically analyzed a group of high risk MDS/AML patients treated by a combination of azacitidine and lenalidomide. In our cohort, the extent of genetic rearrangements was associated with outcome and response to treatment. The size of total genomic aberrations as defined by molecular karyotyping (SNP-array analysis) was a predictive marker for overall survival. TP53 mutations were associated with therapy refractoriness only if accompanied by heavily rearranged chromosomes. This study suggests a potential value of molecular karyotyping as a method to objectivate comprehensively the extent of genetic alterations in high risk patients with complex karyotypes, especially if the clinical value of the size of total genomic aberrations and the fragmentation status of single chromosomes could be evaluated in larger therapy trials. (C) 2015 Elsevier Ltd. All rights reserved
Comprehensive genetic characterization of circulating CD34+cells of MDS patients by FISH- and SNP array analysis
No full textMolecular genomics of cardiac remodeling following changes in intracellular calcium release
No full textMolecular genomics of cardiac remodeling following changes in intracellular calcium release
No full textNext generation sequencing of sex-specific genes in the livers of obese ZSF1 rats
No full textType 2 diabetes induces pathophysiological changes in the liver. The aim of this study was to identify differently expressed genes in the livers of male and female ZSF1 rats (ZDFxSHHF-hybrid, generation F1), a model for type 2 diabetes. Gene expression was investigated using next-generation sequencing (NGS). Selected candidate genes were verified by real-time PCR in the livers of obese and lean rats. 103 sex-different genes, associated to pathways "response to chemical stimulus", "lipid metabolism", and "response to organic substance", were identified. Male-specific genes were involved in hepatic metabolism, detoxification, and secretion, e.g. cytochrome P450 2c11 (Cyp2c11), Cyp4a2, glutathione S-transferases mu 2 (Gstm2), and Slc22a8 (organic anion transporter 3, Oat3). Most female-specific genes were associated to lipid metabolism (e.g. glycerol-3-phosphate acyltransferase 1, Gpam) or glycolysis (e.g. glucokinase, Gck). Our data suggest the necessity to pay attention to sex- and diabetes-dependent changes in pre-clinical testing of hepatic metabolized and secreted drugs. (C) 2015 Published by Elsevier Inc
Gene expression profiling of brains from bovine spongiform encephalopathy (BSE)-infected cynomolgus macaques
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