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)

Duodeno-gastro-esophageal reflux has been thought to induce Barrett's esophagus. Recently, we designed a new duodenal reflux model using rats, and studied sequential morphological changes of esophageal mucosa leading to Barrett's esophagus. A specialized columnar epithelium (SCE) developed 20 weeks after operation. Barrett's epithelium originated from pyloric-foveolar metaplasia of stem cells in the basal layer of the esophageal squamous epithelium. The pyloric-foveolar metaplasia was then followed by the appearance of goblet cells, becoming a typical SCE. The expression of homeobox gene Cdx2 was seen in this process, thereby suggesting a role of Cdx2 in intestinal differentiation of Barrett's esophagus. We noticed the pyloric-foveolar metaplasia followed by the appearance of goblet cells is common to entire gut in regenerative process, and proposed a concept of GRCL (gut regenerative cell lineage), and an implication of GRCL in digestive tract carcinogenesis was discussed.
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PMID:[Pathogenesis of Barrett's esophagus--new findings in the experimental studies of duodenal reflux models]. 1610 Dec 19

The molecular pathogenesis of Barrett's esophagus is poorly understood. Evidence suggests that at a phenotypic level, the metaplastic process begins with the transformation of squamous epithelium in the distal esophagus to cardiac mucosa, which subsequently becomes intestinalized. The homeobox gene Cdx-2 has been shown to be an important transcriptional regulator of embryonic differentiation and maintenance of adult intestinal type epithelium. We hypothesized that Cdx-2 gene expression levels increase with the phenotypic transformation of normal squamous mucosa to the intestinalized columnar mucosa of Barrett's esophagus. Endoscopic biopsies were obtained at the gastroesophageal junction in patients with symptoms of gastroesophageal reflux disease and classified according to histology: normal squamous mucosa (n = 62), cardiac mucosa (n = 19), oxynto-cardiac mucosa (n = 14), and intestinal metaplasia (n = 15). Duodenal biopsies (n = 26) served as the columnar control. After laser capture microdissection and RNA isolation, gene expression levels of Cdx-2 were measured in each tissue type by quantitative reverse transcription polymerase chain reaction. Consistent with its known function, Cdx-2 gene expression levels were highest in duodenal mucosa and nearly absent in squamous epithelium. There was a stepwise increase in Cdx-2 gene expression from cardiac to Barrett's epithelium (P < 0.001). Expression levels of Cdx-2 in cardiac and oxynto-cardiac mucosa were 40-70 times higher and Barrett's mucosa 400 times higher than that found in squamous epithelium. Relative expression of the homeobox gene Cdx-2, known to induce differentiation of intestinal type epithelium, increases in a stepwise fashion during the phenotypic transformation of distal esophageal squamous mucosa to cardiac columnar mucosa and to the intestinalized columnar mucosa of Barrett's esophagus. Therefore, Cdx-2 may be a potential biomarker to detect the early transition to Barrett's esophagus.
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PMID:Cdx-2 expression in squamous and metaplastic columnar epithelia of the esophagus. 1686 57

Esophageal adenocarcinoma develops in response to severe gastroesophageal reflux disease through the precursor lesion Barrett esophagus, in which the normal squamous epithelium is replaced by a columnar lining. The incidence of esophageal adenocarcinoma in the United States has increased by over 600% in the past 40 years and the overall survival rate remains less than 20% in the community. This review highlights some of the signaling pathways for which there is some evidence of a role in the development of esophageal adenocarcinoma. An increasingly detailed understanding of the biology of this cancer has emerged recently, revealing that in addition to the well-recognized alterations in single genes such as p53, p16, APC, and telomerase, there are interactions between the components of the reflux fluid, the homeobox gene Cdx2, and the Wnt, Notch, and Hedgehog signaling pathways.
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PMID:Signaling pathways in the molecular pathogenesis of adenocarcinomas of the esophagus and gastroesophageal junction. 2379 87