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1.
Oncogene ; 29(21): 3163-72, 2010 May 27.
Article in English | MEDLINE | ID: mdl-20305693

ABSTRACT

Sporadic adrenocortical tumours are common, but their pathogenesis is poorly elucidated. In this study, we present a meta-analysis and review of gene expression microarray and comparative genome hybridization (CGH) studies performed to date on these tumours, including our own data. Data of whole genome microarray studies from altogether 164 tumours (97 benign, 67 malignant) and 18 normal tissues were reclassified and reanalysed. Significant gene sets and cytogenetic changes from publications without available genomic data were also examined including 269 benign, 215 malignant tumour and 30 normal tissues. In our experimental study, 11 tumour and four normal samples were analysed by parallel mRNA and CGH profiling. Data were examined by an integrative bioinformatics approach (GeneSpring, Gene Set Enrichment Analysis and Ingenuity Pathway Analysis softwares) searching for common gene expression changes and paralleling chromosome aberrations. Both meta-analysis of available mRNA and CGH profiling data and our experimental study revealed three major pathogenetic pathways: (1) cell cycle, (2) retinoic acid signalling (including lipopolysaccharide/Toll like receptor 4 pathway), (3) complement system and antigen presentation. These pathways include novel, previously undescribed pathomechanisms of adrenocortical tumours, and associated gene products may serve as diagnostic markers of malignancy and therapeutic targets.


Subject(s)
Adrenal Cortex Neoplasms/genetics , Comparative Genomic Hybridization , Genomics , Meta-Analysis as Topic , Chromosome Aberrations , Gene Expression Profiling , Humans , Oligonucleotide Array Sequence Analysis , RNA, Messenger/genetics , RNA, Neoplasm/genetics
2.
Inflamm Res ; 52(8): 322-33, 2003 Aug.
Article in English | MEDLINE | ID: mdl-14504670

ABSTRACT

Differences in drug metabolism among individuals are caused by numerous factors: differences in production and stability of mRNA of xenobiotic metabolizing enzymes, differences in the rate of enzyme synthesis and degradation, or enzyme inhibition. One of the most important reasons is genetic polymorphism of cytochrome P450 genes or cytochrome P450 regulatory factors. Nuclear receptors play great role in the regulation of these genes. The presence of the ligand induces the nuclear receptor to bind to the dimerisation partner and as a hetero/homodimer it can activate the DNA responsive element. In addition, several co-activators, co-repressors and other factors can modulate the effect of nuclear receptors. Hepatic levels of cytochrome P450 enzymes are reduced in multiple models of inflammation or infection. Cytochrome P450 enzymes of four families (CYP1-CYP4) are known to be involved in xenobiotic metabolism. Their genetic polymorphism and regulation are discussed in this review.


Subject(s)
Cytochrome P-450 Enzyme System/genetics , Cytochrome P-450 Enzyme System/metabolism , Genetic Variation , Xenobiotics/metabolism , Gene Expression Regulation , Humans , Models, Genetic , Multigene Family , Polymorphism, Genetic
3.
Biochem Biophys Res Commun ; 286(2): 239-42, 2001 Aug 17.
Article in English | MEDLINE | ID: mdl-11500027

ABSTRACT

The aim of our study was to detect four P450s (CYP1A, CYP2B, CYP2E1, CYP3A) on the basis of selective enzyme activities and protein amount, and to investigate the effect of dexamethasone treatment during liver regeneration. Partial hepatectomy of rats resulted in the loss of CYP1A, CYP2B, CYP2E1, and CYP3A activities. The reduction of enzyme activities and the loss of enzyme protein of CYP2B1/2, CYP2E1, and CYP3A1/2 were the most pronounced. In the case of CYP1A1, only slight decrease was observed. Dexamethasone treatment seems to counteract this loss mainly in the first 12 h.


Subject(s)
Aryl Hydrocarbon Hydroxylases , Cytochrome P-450 Enzyme System/metabolism , Dexamethasone/pharmacology , Liver Regeneration/drug effects , Liver/enzymology , Animals , Cytochrome P-450 CYP1A1 , Cytochrome P-450 CYP2B1/metabolism , Cytochrome P-450 CYP2E1/metabolism , Cytochrome P-450 CYP3A , Hepatectomy , Kinetics , Liver/drug effects , Mixed Function Oxygenases/metabolism , Rats , Steroid Hydroxylases/metabolism
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