Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017168 (gastroesophageal reflux disease)
 11,783 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated TP53 mutation patterns in cancers of the esophagus and cardia of patients coming from Lower Normandy, a region situated in the highest incidence area in Europe. To screen tumor samples, we first used denaturing gradient gel electrophoresis (DGGE), a well-characterized technique which constituted our reference method. Then the results were compared with those obtained by denaturing high performance liquid chromatography (DHPLC), a recent and automatic screening technology. Analysis of the TP53 mutations profile showed that the detected alterations were mainly point mutations. Ninety-seven percent (33/34) of esophageal squamous cell carcinoma samples presented at least one mutation or polymorphism. The proportion of somatic, non-silent and sequence-confirmed mutations was 76% (26/34). The most common substitutions were G-->A transitions, which could be related to nitrosamines, acetaldehyde or factors prone to producing mucosal irritation, like hot beverages. G-->T transversions, which were also frequently detected, could originate from benzo[a]pyrene in tobacco smoke. A-->T transversions were not revealed in our series, which constitutes a discordance with mutational spectra already performed in north-western France. Concerning adenocarcinoma of the esophagus and cardia, the alteration frequency was 69% (11/16), with a majority of G-->A transitions at CpG dinucleotides. They are probably related to endogenous process mediated by inflammatory diseases like gastro-esophageal reflux and Barrett's esophagus. The main advantage provided by DHPLC was its ease of application. However, the optimization steps turned out to be quite critical, especially for sequences with high melting temperatures embedded in lower melting temperature fragments. Considering only the common sequences analyzed by the two techniques, four of the 46 positive samples detected by DGGE were not revealed by DHPLC. This result stresses the limited sensitivity of DHPLC compared with DGGE under the conditions described in this study.
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PMID:Simultaneous use of DGGE and DHPLC to screen TP53 mutations in cancers of the esophagus and cardia from a European high incidence area (Lower Normandy, France). 1271 98

Omeprazole is a drug used for treating gastro-oesophageal reflux disease and duodenal ulcers. Omeprazole induces a xenobiotic-metabolizing enzyme, cytochrome P450 1A1 (CYP1A1), as its ligand by aryl hydrocarbon receptor (AhR) activation without binding. CYP1A1-inducible chemicals, such as benzo[a]pyrene and 2,3,7,8-tetrachlorodibenzo-p-dioxin, are known to have adverse effects (i.e. carcinogenesis, mutagenesis and malformation). Unlike these typical AhR activators, omeprazole has shown no experimental evidence of carcinogenic activity. The possibility, however, remains that omeprazole may aggravate the effect of environmental carcinogens through CYP1A1 induction. We exposed benzo[a]pyrene and omeprazole simultaneously to human and mouse hepatoma cells to investigate the synergistic effect of these chemicals. Contrary to our prediction, cytotoxicity of benzo[a]pyrene was inhibited by the omeprazole exposure in a dose-dependent manner. Omeprazole did not alter CYP1A1 mRNA and protein levels induced by benzo[a]pyrene. The 7-ethoxy-resorufin-O-deethylase assay revealed that omeprazole inhibited CYP1A1 enzyme activity. Kinetic analysis also demonstrated that it is a competitive inhibitor for CYP1A1. The K(m) value of omeprazole against CYP1A1 activity was 50.1 microM. We conclude that the effects of omeprazole on CYP1A1 involve not only induction through AhR activation but also inhibition of its enzyme activity, and that the protective effect of omeprazole against benzo[a]pyrene cytotoxicity depends on the latter.
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PMID:Omeprazole alleviates benzo[a]pyrene cytotoxicity by inhibition of CYP1A1 activity in human and mouse hepatoma cells. 1879 72