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)

Studies in human beings and animals have shown that esophageal exposure to duodenal and gastric contents may be important for the development of Barrett's esophagus and its complications, including adenocarcinoma and epidermoid carcinoma. Diethylnitrosamine (DEN) is a carcinogen that stimulates the development of epidermoid carcinoma in the esophagus of mice. The aim of this study was to evaluate the effect of gastroduodenal and gastric content reflux on induction of esophageal carcinogenesis. Gastroesophageal reflux (GER) and gastroduodenoesophageal reflux (GDER) were produced by cardioplasty and esophagoduodenostomy. The chosen carcinogen was DEN, diluted in drinking water, given 3 days a week for 20 consecutive weeks. One hundred Wistar female rats were divided into six groups, as follows: group 1 (18 rats), cardioplasty without DEN; group 2 (18 rats), cardioplasty with DEN; group 3 (10 rats), only water; group 4 (17 rats), cardioplasty with DEN; group 5 (17 rats), esophagoduodenostomy with DEN; group 6 (20 rats), only DEN. GER in isolation induced papillomatosis or ulceration in 22.2% of rats and, when associated with DEN, induced papillomatosis in 61.1% of rats. GDER in isolation induced marked esophagitis in 61.1% of rats, Barrett's esophagus in 16.7% and esophageal adenocarcinoma in 16.7%; when associated with DEN, 23.5% of rats presented marked esophagitis, papillomatosis or ulceration, whereas 76.5% had esophageal carcinoma, with 70.6% epidermoid carcinoma and 5.9% adenocarcinoma. Rats treated with water alone did not show histologic abnormalities of the esophageal mucosa. Rats treated with DEN alone developed papillomas in 50.0% of the cases and remained histologically unchanged in 50.0%. There was no development of low- or high-grade dysplasia in any group. The conclusions are that (1) GDER is significantly more deleterious to esophageal mucosa than GER; (2) in this study, GER did not present carcinogenic potential in relation to the esophagus; (3) GDER in isolation is an esophageal carcinogen, producing Barrett's esophagus and esophageal adenocarcinoma; (4) esophageal oncogenesis caused by GDER is potentiated by DEN, inducing esophageal epidermoid carcinoma; (5) in this study, DEN in isolation did not generate tumors in the esophagus of rats.
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PMID:Influence of surgically induced gastric and gastroduodenal content reflux on esophageal carcinogenesis--experimental model in Wistar female rats. 1046 42

Oxidative damage has long been related to carcinogenesis in human cancers and animal cancer models. Recently a rat esophageal adenocarcinoma (EAC) model was established in our laboratory by using esophagoduodenal anastomosis (EDA) plus iron supplementation. Our previous study suggested that iron supplementation enhanced inflammation and the production of reactive nitrogen species in the esophageal epithelium, which could contribute to esophageal adenocarcinogenesis. Here we further characterized oxidative damage in this model. We were particularly interested in how excess iron was deposited in the esophagus, and which cells were targeted by oxidative damage. Male Sprague-Dawley rats received iron supplementation (50 mg Fe/kg/month, i.p.) starting 4 weeks after EDA. The animals were killed at 11, 30 or 35 weeks after surgery. EAC appeared as early as week 11 after surgery, and increased over time, up to 60% at 35 weeks after surgery. All EACs were well-differentiated mucinous adenocarcinoma at the squamocolumnar junction. Iron deposition was found at the squamocolumnar junction and in the area with esophagitis. Esophageal iron overload could result from transient increase of blood iron after i.p. injection, and the overexpression of transferrin receptor in the premalignant columnar-lined esophagus (CLE) cells. Oxidative damage to DNA (8-hydroxy-2'-deoxyguanosine), protein (carbonyl content) and lipid (thiobarbituric acid reactive substance) in the esophagus was significantly higher than that of the non-operated control. CLE cells were believed to be the target cells of oxidative damage because they overexpressed heme oxygenase 1 and metallothionein, both known to be responsive to oxidative damage. We propose that oxidative damage plays an important role in the formation of EAC in the EDA model, and a similar situation may occur in humans with gastroesophageal reflux and iron over-nutrition.
Carcinogenesis 2000 Feb
PMID:Oxidative damage in an esophageal adenocarcinoma model with rats. 1065 66

Recent studies have demonstrated that refluxed duodenal contents cause esophageal carcinoma in rats without exposure to carcinogens. The histopathological spectrum of these carcinomas includes squamous-cell carcinoma, adenocarcinoma and adenosquamous carcinoma. Pure adenocarcinomas are thought to arise in areas of columnar metaplasia adjacent to the anastomosis, similar to Barrett's esophagus in humans. In contrast, the histogenesis of adenosquamous carcinomas is unclear. The purpose here was to investigate the pathogenesis of esophageal adenosquamous carcinomas in a time-course experiment of chronic duodenal-content reflux without carcinogen. Forty-two 8-week-old male Sprague-Dawley rats were divided into seven groups and exposed to duodenal-content esophageal reflux during 10, 15, 20, 25, 30, 35 and 40 weeks, respectively. All animals underwent an esophagojejunostomy with gastric preservation in order to produce chronic esophagitis. The rats received a standard diet without addition of carcinogens. An increasing incidence of glandular metaplasia and carcinoma was observed over the time course, starting at 20 weeks. After 40 weeks of reflux, multiple foci of glandular metaplasia and adenosquamous carcinoma were found in 83 and 50% of the animals, respectively. Most of the carcinomas occurred in the middle and proximal esophagus and had a dual pattern of differentiation, glandular and squamous. These findings confirm that duodenal content reflux alone has a carcinogenic effect. We propose that chronic duodenal reflux induces the development of metaplastic cells with glandular differentiation from the stem cells of squamous epithelium, and that glandular metaplastic foci are the morphological element from which tumors with a dual pattern of differentiation arise.
Carcinogenesis 2000 Aug
PMID:Duodenal-content reflux esophagitis induces the development of glandular metaplasia and adenosquamous carcinoma in rats. 1091 Sep 63

We reviewed the histopathological features for the diagnosis of reflux esophagitis and gastroesophageal reflux disease(GERD) including carcinogenesis of the esophagus. Histologically, the presence of capillary dilatation, elongation of papillary, hyperplasia of basal layer, inflammatory cells-infiltration, balloon cells in the epithelium, and ulceration were evaluated in GERD cases. Although, histopathological changes were not clear in endoscopic-negative GERD cases, immunohistochemical examination with cell cycle protein(PCNA, p21, and p27) revealed the same abnormalities with GERD cases. In Japan, the majority cases of GERD are evaluated in grade according to Los Angeles system, therefore the prevalence of Barrett's esophagus and cancer is very low. We hypothesize that esophageal squamous cell carcinoma arising from GERD different from Barrett's cancer sequence, and clinicopathological long-term follow up will be required to assess the carcinogenesis including gene analysis.
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PMID:[Histopathological diagnosis in reflux esophagitis]. 1100 8

Surgically induced duodenal reflux results in cancer development in the rat esophagus. One proposed mechanism of carcinogenesis relies on the production of carcinogens in the presence of bacterial overgrowth. Against this background, intestinal microflora in the rat jejunum was analyzed before and after reflux-inducing surgery. Total gastrectomy and esophagojejunostomy were performed on Sprague-Dawley rats to produce esophageal reflux of duodenal juice (n = 12). Three days before surgery they were randomized into three groups: animals which received tap water; animals which received acidified water at pH 1.8; and animals subjected to oral decontamination with triple antibiotics. During surgery and at autopsy after 2 weeks, intestinal juice was aspirated and analyzed immediately for bacterial content. The physiologic microflora of the rat jejunum contained Lactobacillus spp. and Bacteroides spp., both of which were resistant to the antibiotic regimen. Bacterial overgrowth with fecal bacteria was found following surgery. Acidified water did not alter the intestinal microflora. Triple antibiotics eliminated Escherichia coli and Proteus spp. and reduced the concentration of Enterococcus spp. Bacterial overgrowth by bacteria of the fecal flora occurs in the rat model of esophageal adenocarcinoma with the potential to catalyze the production of carcinogens.
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PMID:Evaluation of the intestinal microflora in the rat model for esophageal adenocarcinoma. 1100 30

The incidence of esophageal adenocarcinoma is increasing rapidly. In rats, surgically induced duodenoesophageal reflux is carcinogenic. One proposed mechanism of carcinogenesis is based on the reaction of physiological bile acids with nitrite to produce carcinogenic N:-nitroso amides. To test this hypothesis, duodenal juice was analyzed for endogenously formed N:-nitroso bile acids and its genotoxicity was determined. Esophagojejunostomy was performed on 15 Sprague-Dawley rats to produce duodeno-esophageal reflux. At the time of surgery and 2 and 6 weeks later, duodenal contents were aspirated and analyzed immediately. High performance liquid chromatography coupled to tandem mass spectrometry was used to detect bile acids and their nitroso derivates. Genotoxicity was assessed using a micronucleus test. The characteristic pattern of bile acid derivatives, with taurocholic acid (TCA) and glycocholic acid (GCA) as the predominant conjugates, was detected in all samples. However, even selective reaction monitoring experiments failed to demonstrate the presence of any N:-nitroso-TCA or N:-nitroso-GCA. In addition, other nitroso derivatives could not be detected in any of the samples by neutral loss experiments monitoring the loss of nitric oxide (detection limit 0.1% of the concentration of TCA). All samples were cytotoxic, but neither the preoperative nor the postoperative samples were genotoxic. Duodenal juice was cytotoxic but not genotoxic. Tumorigenesis of esophageal adenocarcinoma in the rodent model could not be linked to a specific carcinogen, especially not to nitroso bile acids. Chronic inflammation is likely to be the mechanism of carcinogenesis by duodenogastric reflux.
Carcinogenesis 2000 Nov
PMID:Duodenogastric reflux and foregut carcinogenesis: analysis of duodenal juice in a rodent model of cancer. 1106 71

Helicobacter pylori (H. pylori) infection is recognized to be a pathogen of various gastro-duodenal disease. Eradication therapy of H. pylori reduces the recurrence of gastro-duodenal ulcer, improves gastritis histologicaly, and is suggested to act an certain role in protection against gastric carcinogenesis. Although, several studies show uncomfortable results arise after H. pylori infection was cured. These studies suggest that gastro-esophageal reflux disease (GERD) and gastro-doudenal erosion may increase after successful eradication of H. pylori. Recently, adenocarcinoma of the gastric cardia and esophagus increase in incidence. Reflux esophagitis and Barrett's esophagus are recognized as precancerous lesion of esophageal adenocarcinoma. It is uncertain the association of newly occurrence of GERD after H. pylori eradication and increase of esophageal adenocarcinoma. Although GERD may lead to adenocarcinoma, long term observations is necessary after H. pylori eradication.
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PMID:[Occurrence of upper gastrointestinal tract disease after Helicobacter pylori eradication]. 1121 8

Since the discovery of Helicobacter pylori(H. pylori), causal linkage between H. pylori infection and some of gastric disease has been generally accepted from the results of many studies. Indeed the usefulness of H. pylori eradication therapy for acute gastritis, peptic ulcer, gastric polyp and MALT lymphoma etc. has been reported. In the low grade MALT lymphoma, the regression rate by this therapy is about 70%. On the other hand, we should pay the caution to several adverse effects, such as drug resistance and GERD, of H. pylori eradication therapy. However, based on the several results of comparative studies between antibiotic therapy and the other one, the antibiotic therapy for peptic ulcer is only covered by national health insurance at present. The reversibility of gastric precancerous conditions such as mucosal atrophy, intestinal metaplasia and dysplasia by antibiotic therapy has been studied, but its significance is not clear yet. In animal experiment, H. pylori infection induced gastric adenocarcinoma in Mongolian Gerbils. However, this phenomenon is limited to this kind of animal only. To proof the causal link between H. pylori infection and genesis of gastric cancer in human being, clinical intervention trials are ongoing in the world. If these trials can clarify it, the H. pylori eradication therapy will be established as preventive measure for gastric carcinogenesis.
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PMID:[Helicobacter pylori & gastric disease]. 1130 2

The incidence rate of esophageal adenocarcinoma (EAC) has increased sharply in the past 30 years. Many risk factors have been identified and gastroesophageal reflux disease (GERD) is the most important one. Columnar-lined esophagus, resulting from GERD, is recognized as a key precursor lesion of EAC. In this article, we review the studies on EAC in humans and animal models. We propose that the pathogenesis of EAC is mainly driven by inflammation and oxidative stress, which are augmented by iron overload. The overproduction of prostaglandin E2 and leukotriene B4 and overexpression of their receptors are believed to be major factors in exacerbating inflammation and oxidative stress. Based on this mechanistic understanding, antioxidants, inhibitors of arachidonic acid metabolism enzymes and receptor antagonists of certain eicosanoids are proposed as potential chemopreventive agents for EAC in future studies.
Carcinogenesis 2001 Aug
PMID:Esophageal adenocarcinoma: a review and perspectives on the mechanism of carcinogenesis and chemoprevention. 1147 Jul 39

Oesophageal adenocarcinoma is one of the most deadly human malignancies. Gastro-oesophageal reflux disease (GERD) has been established as a strong risk factor for oesophageal adenocarcinoma, and more than 40% of adult Americans experience regular GERD symptoms. GERD can be complicated by oesophagitis, and by replacement of oesophageal squamous mucosa with metaplastic, intestinal-type epithelium (Barrett's oesophagus) that is predisposed to malignancy. Cancers in Barrett's oesophagus arise through a sequence of genetic alterations which endow unlimited proliferative capacity upon the cells by affecting components of the cell cycle clock apparatus-the pivotal molecular machinery in the cell nucleus that controls whether a cell will proliferate, differentiate, become quiescent or die. This report describes how the genetic abnormalities that have been recognized in Barrett's oesophagus might promote carcinogenesis through effects on the cell cycle clock machinery. The goal of this review is to provide the clinician with a useful conceptual basis for evaluating studies on the molecular mechanisms underlying the progression from metaplasia to carcinoma in Barrett's oesophagus.
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PMID:Review article: a conceptual approach to understanding the molecular mechanisms of cancer development in Barrett's oesophagus. 1147 11


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