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

Barrett's esophagus (BE) is a metaplastic change of the squamous esophageal epithelium to columnar gastric or intestinal-like epithelium. BE is associated with long-standing gastroesophageal reflux disease and carries an increased risk for dysplasia and adenocarcinoma. Little if any is known regarding the differentiation state of esophageal metaplasia and its relationship to carcinogenesis. In this study, we investigated the potential of villin, a cytoskeletal protein, and Ep-CAM, a glandular epithelial glycoprotein, to serve as markers for enterocytic differentiation in BE at the molecular level. Endoscopic mucosal biopsy samples of normal esophagus, BE, stomach and duodenum were collected from 23 patients with BE. Biopsies were analyzed for villin and Ep-CAM expression by immunoblotting, and in some cases for the presence of microvilli by electron microscopy. By mapping of BE segments in 6 patients, correlations were also made between the histologic evidence of metaplasia and villin expression. Villin was uniformly expressed in all duodenal samples but was not detected in normal esophagus and stomach. In BE biopsies, villin expression was limited to the subset of patients whose adjacent biopsies showed microvilli by electron microscopy. In several patients studied, however, the expression of villin and the epithelial glycoprotein Ep-CAM differed among various regions of esophageal metaplasia within the same patient. Mapping studies failed to reveal any correlation among histologic evidence of metaplasia, dysplasia and villin expression and confirmed the multifocal heterogeneity of villin expression in BE. Preliminary data of 4 adenocarcinoma patients studied showed that villin expression was absent in 3 and very low in 1 patient. Ep-CAM was highly expressed in all adenocarcinoma patients. Our results show that BE represents a complex epithelium with significant heterogeneity in antigen expression and ultrastructural morphologic features. This molecular heterogeneity supports the presence of different stages of differentiation within the same epithelium.
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PMID:Multifocal heterogeneity in villin and Ep-CAM expression in Barrett's esophagus. 860 65

Proton pump inhibitors (PPIs) have become of great importance for the treatment of peptic ulcer disease and gastroesophageal reflux disease. However, these drugs have several adverse effects, including worsening of corpus atrophic gastritis in patients with H. pylori infection, various histological changes including fundic gland-type polyps, inhibition of glycoprotein production, and hypergastrinemia. On the other hand, it has been reported that rebamipide, a gastroprotective drug, has the potential to increase mucous secretion and basically regulate physiological defensive functions aimed to maintain tissue integrity. In this study, we attempted to clarify whether rebamipide improves morphological changes and hypergastrinemia after administration of omeprazole (OPZ) for 1 year in rats. Eight-week-old male Wistar rats were used. Rats were divided into four groups according to diet as follows: 100 mg/kg body weight OPZ group, 100 mg/kg body weight OPZ and 30 mg/kg body weight rebamipide (OPZ + trebanipide group), 30 mg/kg body weight rebamipide, and normal diet (CRF-1). Morphological changes in gastric mucosa in all groups were studied using hematoxylin and eosin staining, periodic acid-Schiff staining, and immunohistochemical staining for alpha-amylase. Serum gastrin level and basal acid secretion were also examined. In the OPZ group, cystic degenerations with amorphous eosinophilic contents, decreased mucous secretion, decreased chief cells, and development of pancreatic acinar cell metaplasia were detected. However, in the OPZ+rebamipide group, these morphological changes were significantly milder than in the OPZ group. Serum gastrin level and basal acid secretion in the OPZ group increased significantly compared to those in the control group. But these factors in the OPZ+rebamipide group were almost normalized (similar to those of control animals). In conclusion, long-term OPZ treatment causes various morphological changes, hypergastrinemia, and basal acid hypersecretion. The present results suggest that rebamipide contributes to reducing these adverse effects caused by long-term OPZ treatment in rats.
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PMID:Rebamipide contributes to reducing adverse effects of long-term administration of omeprazole in rats. 1734 92

Fibrillar collagens provide the most fundamental platform in the vertebrate organism for the attachment of cells and matrix molecules. We have identified specific sites in collagens to which cells can attach, either directly or through protein intermediaries. Using Toolkits of triple-helical peptides, each peptide comprising 27 residues of collagen primary sequence and overlapping with its neighbours by nine amino acids, we have mapped the binding of receptors and other proteins on to collagens II or III. Integrin alpha2beta1 binds to several GXX'GER motifs within the collagens, the affinities of which differ sufficiently to control cell adhesion and migration independently of the cellular regulation of the integrin. The platelet receptor, Gp (glycoprotein) VI binds well to GPO (where O is hydroxyproline)-containing model peptides, but to very few Toolkit peptides, suggesting that sequence in addition to GPO triplets is important in defining GpVI binding. The Toolkits have been applied to the plasma protein vWF (von Willebrand factor), which binds to only a single sequence, identified by truncation and amino acid substitution within Toolkit peptides, as GXRGQOGVMGFO in collagens II and III. Intriguingly, the receptor tyrosine kinase, DDR2 (discoidin domain receptor 2) recognizes three sites in collagen II, including its vWF-binding site, although the amino acids that support the interaction differ slightly within this motif. Furthermore, the secreted protein BM-40 (basement membrane protein 40) also binds well to this same region. Thus the availability of extracellular collagen-binding proteins may be important in regulating and facilitating direct collagen-receptor interaction.
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PMID:Cell-collagen interactions: the use of peptide Toolkits to investigate collagen-receptor interactions. 1836 67

Esophageal adenocarcinoma (EAC) has become a major concern in Western countries due to rapid rises in incidence coupled with very poor survival rates. One of the key risk factors for the development of this cancer is the presence of Barrett's esophagus (BE), which is believed to form in response to repeated gastro-esophageal reflux. In this study we performed comparative, genome-wide expression profiling (using Illumina whole-genome Beadarrays) on total RNA extracted from esophageal biopsy tissues from individuals with EAC, BE (in the absence of EAC) and those with normal squamous epithelium. We combined these data with publically accessible raw data from three similar studies to investigate key gene and ontology differences between these three tissue states. The results support the deduction that BE is a tissue with enhanced glycoprotein synthesis machinery (DPP4, ATP2A3, AGR2) designed to provide strong mucosal defenses aimed at resisting gastro-esophageal reflux. EAC exhibits the enhanced extracellular matrix remodeling (collagens, IGFBP7, PLAU) effects expected in an aggressive form of cancer, as well as evidence of reduced expression of genes associated with mucosal (MUC6, CA2, TFF1) and xenobiotic (AKR1C2, AKR1B10) defenses. When our results are compared to previous whole-genome expression profiling studies keratin, mucin, annexin and trefoil factor gene groups are the most frequently represented differentially expressed gene families. Eleven genes identified here are also represented in at least 3 other profiling studies. We used these genes to discriminate between squamous epithelium, BE and EAC within the two largest cohorts using a support vector machine leave one out cross validation (LOOCV) analysis. While this method was satisfactory for discriminating squamous epithelium and BE, it demonstrates the need for more detailed investigations into profiling changes between BE and EAC.
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PMID:Whole genome expression array profiling highlights differences in mucosal defense genes in Barrett's esophagus and esophageal adenocarcinoma. 2182 65