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)

Omeprazole is a potent and effective antisecretory drug. Benefits in gastric and duodenal ulceration nevertheless seem marginal because standard treatments are very effective. More obvious advantages are discernible in oesophageal reflux disease where more profound acid inhibition may be needed to obtain symptom relief. Fears of important adverse effects either through inducing ECL cell hyperplasia or outright carcinogenesis, do not seem firmly founded, nor is there convincing evidence of significant interactions with other xenobiotics. Nevertheless, continued caution seems justified.
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PMID:Omeprazole. 178 9

Omeprazole, one of a new group of antisecretory drugs, is a substituted benzimidazole that does not exhibit the anticholinergic or histamine H2 antagonistic properties of drugs such as cimetidine. This agent suppresses gastric acid secretion by inhibiting the proton pump mechanism, thereby blocking the final step of acid secretion. Omeprazole is significantly more effective than the histamine H2 receptor antagonists in eliminating acid secretion; thus, it may be beneficial in patients who are resistant to these agents. Omeprazole is indicated for severe erosive esophagitis, gastroesophageal reflux disease that does not respond to H2 receptor antagonists, and hypersecretory diseases such as Zollinger-Ellison syndrome and systemic mastocytosis. Because of the theoretic risk of carcinogenesis, short-term therapy is recommended, although long-term therapy is required for hypersecretory diseases.
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PMID:Omeprazole: a new approach to gastric acid suppression. 232 97

After the 12- and 14-month administration of the preparation gricin to ten white and two bare (nunu) mice in hepatic tissue in addition to diffuse and nodular hyperplasia hepatomas developed. The ultrastructural changes of tumour cells were not typical and involved above all GER, nuclei and nucleoli. They corresponded to findings of experimental carcinogenesis and human hepatomas.
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PMID:[Hepatoma after long-term administration of griseofulvin]. 728

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

When the distal esophagus is lined by a segment of columnar epithelium that is abnormal either because it is extensive or because it has intestinal features, the condition is called Barrett's esophagus. Traditionally, Barrett's esophagus has been associated with severe gastroesophageal reflux disease (GERD) and with a high risk for adenocarcinoma. Recently, investigators have shown that short segments of intestinal metaplasia can be found frequently in the distal esophagus of patients who have few signs and symptoms of GERD. For these patients, the risk for carcinogenesis is not clear. This article summarizes the diagnostic and clinical features of Barrett's esophagus and presents an approach to the management of patients with this fascinating disorder.
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PMID:Barrett's esophagus. 870 59

Esophageal adenocarcinoma arises from Barrett's esophagus, which is induced by gastro-esophageal reflux. This refluxate often contains duodenal contents, whose backflow triggers gastric carcinoma, suggesting the hypothesis that refluxed duodenal contents cause esophageal carcinoma. This study examines the role of duodenal and gastric reflux in the absence of exogenous carcinogens in esophageal carcinogenesis. Wistar male rats, 120 in all, each weighing approximately 250 g, were used. Three experimental procedures were performed to produce gastro-duodeno-esophageal reflux, duodeno-esophageal reflux and gastro-esophageal reflux, for comparison with 2 control procedures, Roux-en-Y reconstruction and a sham operation. The animals were fed a standard diet and were examined 50 weeks after surgery. While no carcinoma was found among the 16 gastro-esophageal-reflux, 11 Roux-en-Y and 12 sham-operation animals, 10 of the 12 animals with gastro-duodeno-esophageal reflux (83%) and 10 of the 13 with duodeno-esophageal reflux (77%) developed esophageal carcinoma. The difference between groups was significant (p < 0.001). Two animals with gastro-duodeno-esophageal reflux had esophageal double and triple carcinomas respectively. Of the 23 carcinomas, 16 were adenocarcinoma, 4 adenosquamous carcinoma, and 3 squamous-cell carcinoma. Adenocarcinoma developed from the columnar-lined epithelium near the esophago-jejunostoma, while adenosquamous and squamous-cell carcinoma arose from the squamous esophagitis. These observations demonstrate that refluxed duodenal contents per so are responsible for esophageal carcinogenesis.
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PMID:Reflux of duodenal or gastro-duodenal contents induces esophageal carcinoma in rats. 876 May 98

The development of columnar lined epithelium with intestinal metaplasia in the distal esophagus is a possible, but not a necessary, end stage of advanced gastroesophageal reflux disease. Currently, research is focused on the carcinogenesis of Barrett's carcinoma and the metaplasia-dysplasia carcinoma sequence, since it is a malignoma with the highest increasing incidence in Western industrial countries. Possible causes of the above-mentioned sequence are excessive acid, duodenogastric reflux, and genetic factors. A curative surgical approach is the radical R-0 resection. Some centers prefer the transmediastinal esophagectomy. Others prefer the transthoracic en bloc esophagectomy. Reconstruction can be done with the stomach and the colon. Patients with advanced disease probably benefit best from multimodal therapy with neoadjuvant radiochemotherapy.
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PMID:[Barrett carcinoma as a tumor entity with special therapy consequences]. 993 28

The expression of cytochrome (CYP) P450 enzymes in human oesophageal mucosa was investigated in a total of 25 histologically non-neoplastic surgical tissue specimens by using specific antibodies in immunoblots and by RT-PCR mRNA analysis. The presence of CYP1A, 2E1, 3A and 4A enzymes was demonstrated by both techniques; CYP2A reactive protein was also detected by immunoblot. The presence of CYP4B1 mRNA was established but no specific antibody was available for detection of the corresponding protein by immunoblot. CYP2B6/7 mRNA was not detected in any sample. The mRNA transcripts for CYP1A1, 2E1, 4A11 and 4B1 were consistently detected in the majority of samples (>84%), whereas CYP1A2 mRNA was only detected in 11 of 19 specimens examined. An RT-PCR method to differentiate CYP3A4 and 3A5 mRNA was developed. This demonstrated CYP3A5 mRNA expression in all samples tested, whereas CYP3A4 mRNA was not detectable, suggesting that CYP3A5 is the major CYP3A protein in human oesophagus. There were significant interindividual variations in the amount of proteins, ranging from 8-fold for CYP4A to 43-fold for CYP2E1. For each patient, data on exposure to risk factors for oesophageal cancer were available, including tobacco smoke, alcohol, gastro-oesophageal reflux and hot beverage consumption. None of these risk factors or other patient characteristics (age, sex, tumour location and tumour stage) were correlated with the protein level of the individual CYP enzymes as determined by quantitation of immunoblot staining. However, the small series of samples precludes any strong conclusion concerning the lack of such correlations. There were no differences between squamous cell carcinomas and adenocarcinomas in either the qualitative or quantitative expression of the CYP enzymes. These data demonstrate that a range of CYP enzymes are expressed in human oesophageal mucosa and indicate that this tissue has the capacity to activate chemical carcinogens to reactive DNA binding metabolites.
Carcinogenesis 1999 Feb
PMID:Characterization of cytochrome P450 expression in human oesophageal mucosa. 1006 60

Intestinalized epithelium in traditional long-segment Barrett's esophagus (BE) shows increased proliferative activity, which is postulated to be an early step in the metaplasia-dysplasia-carcinoma sequence. The aim of this study was to evaluate the proliferative activity of intestinalized epithelium of the distal esophagus and gastroesophageal junction (IMEGEJ). Tissue sections from 78 consecutive patients (20 with IMEGEJ, 58 without IMEGEJ) who had elective upper gastrointestinal endoscopy over a 6-month period were immunohistochemically stained with MIB-1, the Ki-67 proliferation-antigen-associated marker, for evaluation of the crypt MIB-1 proliferation index (PI), size of the proliferative zone (PZ), and the presence of surface epithelial staining. Data from the IMEGEJ and non-IMEGEJ groups, and from 15 age-matched patients with traditional long-segment BE (>3.0 cm), were compared statistically. IMEGEJ patients showed a statistically significant increase in the mean crypt PI compared with non-IMEGEJ controls (21.9+/-19.5 v 14.3+/-9.3; P=.01). In addition, IMEGEJ cases showed an increase in the mean crypt PZ (52.3+/-16.4 v 45.2+/-17.2; P=.05), and a trend toward an increase in the percentage of cases with MIB-1-positive surface epithelial cells (50% v 33%, P=.18). Patients with IMEGEJ did not differ from patients without IMEGEJ with respect to any other clinical or histological feature, including signs or symptoms of gastroesophageal reflux disease and presence or absence of esophagitis or carditis. The MIB-1 results of the patients with long-segment BE (MIB-1 PI = 22.6+/-20.5, MIB-1 PZ = 51.8+/-19.6, proportion of cases with MIB-1-positive surface cells = 66%) were similar to those with IMEGEJ. Intestinalized epithelium in the distal esophagus or gastroesophageal junction shows increased proliferative activity in comparison with patients without intestinalized epithelium. This finding supports an increased risk of carcinogenesis in patients with IMEGEJ.
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PMID:Proliferative characteristics of intestinalized mucosa in the distal esophagus and gastroesophageal junction (short-segment Barrett's esophagus): a case control study. 1020 62

A metaplastic process, in which native squamous epithelium of the distal esophagus is replaced by columnar epithelium, is known as Barrett esophagus (BE). Over the past years, intestinal metaplasia was recognized as a marker for BE. The risk for the development of esophageal adenocarcinoma in a patients with BE is much higher when compared to the normal population. Duodeno-gastro-esophageal reflux is supposed to play a role in the pathogenesis of BE and rising incidence of adenocarcinoma of the esophagus. With current therapeutic options, when clinical manifestation of this cancer occurs, it is too late for cure in the majority of patients. Therefore, attention should be focused on early diagnosis, for which molecular genetic techniques might become available. Current data on genetic alterations involved in carcinogenesis of BE are discussed. Grading of dysplasia in BE carries important clinical consequences for the individual patient: intensification of endoscopic surveillance or 'prophylactic esophagectomy'. Several morpho- and/or cytometric parameters may be used for discrimination between different grades of dysplasia in BE. Therefore, a new and original algorythm for the potential application of quantitative pathology in grading of dysplasia in patients with BE has been proposed. Molecular biology together with image analysis of histological spectrum of BE enable better understanding of the mechanisms of malignant degeneration and might ultimately lead to targeted cancer prevention and/or therapeutic interventions.
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PMID:Barrett esophagus and cancer: pathogenesis, carcinogenesis, and diagnostic dilemmas. 1042 62


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