Linked Life Data

17849424

Source:http://linkedlifedata.com/resource/pubmed/id/17849424

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2008-3-13
pubmed:abstractText
Nitric oxide (NO) has been implicated as a potential causative factor for endogenous p53 mutations in gastrointestinal malignancy. To investigate the role of NO in esophageal adenocarcinoma (EADC), we studied patterns of p53 mutations, expression of inducible nitric oxide synthase (iNOS) and the tissue accumulation of nitrotyrosine (NTS), a stable reaction product of NO and a marker for cellular protein damage, in human premalignant and malignant esophageal epithelia. Tissues were obtained from patients with gastroesophageal reflux disease (GERD)-induced esophagitis (n = 76), Barrett's esophagus (BE; n = 119) and primary EADC (n = 54). DNA sequencing was used to characterize p53 mutations, RT-PCR to study iNOS mRNA expression, and immunohistochemistry to study NTS. Relative to self-matched normal epithelia, a progressive increase in iNOS mRNA expression was seen in GERD (30%; 23/76), BE (48%; 57/119), and EADC (63%; 34/54) tissues (P < 0.001). Among patients with EADC, elevated levels of NTS immunoreactivity were more frequent in tumors with p53 mutations (11/21; 52%) compared with tumors with wild-type p53 (9/33; 27%; P = 0.063), and specifically in tumors with p53 mutations at CpG dinucleotides (10/12; 83%) compared with non-CpG p53 mutations (1/9; 11%; P = 0.008). The increasing frequency of iNOS (mRNA) overexpression in GERD, BE and EADC supports the hypothesis that an active inflammatory process, most likely a consequence of GERD, underlies molecular progression to EADC. The highly significant association between NTS, reflecting chronic NO-induced cellular protein damage, and endogenous p53 mutations at CpG dinucleotides, provides further evidence for a molecular link between chronic inflammation and esophageal malignancy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1098-2744
pubmed:author
pubmed:copyrightInfo
(c) 2007 Wiley-Liss, Inc.
pubmed:issnType
Electronic
pubmed:volume
47
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
275-85
pubmed:dateRevised
2011-10-27
pubmed:meshHeading
pubmed-meshheading:17849424-Adenocarcinoma, pubmed-meshheading:17849424-Adolescent, pubmed-meshheading:17849424-Adult, pubmed-meshheading:17849424-Aged, pubmed-meshheading:17849424-Aged, 80 and over, pubmed-meshheading:17849424-Barrett Esophagus, pubmed-meshheading:17849424-Chronic Disease, pubmed-meshheading:17849424-Esophageal Neoplasms, pubmed-meshheading:17849424-Female, pubmed-meshheading:17849424-Genes, p53, pubmed-meshheading:17849424-Humans, pubmed-meshheading:17849424-Inflammation Mediators, pubmed-meshheading:17849424-Male, pubmed-meshheading:17849424-Middle Aged, pubmed-meshheading:17849424-Nitric Oxide, pubmed-meshheading:17849424-Nitric Oxide Synthase Type II, pubmed-meshheading:17849424-Point Mutation, pubmed-meshheading:17849424-Tumor Suppressor Protein p53, pubmed-meshheading:17849424-Tyrosine
pubmed:year
2008
pubmed:articleTitle
Inducible nitric oxide synthase, nitrotyrosine and p53 mutations in the molecular pathogenesis of Barrett's esophagus and esophageal adenocarcinoma.
pubmed:affiliation
Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't