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)

MUC4 is a membrane-bound mucin known to participate in tumor progression. It has been shown that MUC4 pattern of expression is modified during esophageal carcinogenesis, with a progressive increase from metaplastic lesions to adenocarcinoma. The principal cause of development of esophageal adenocarcinoma is the gastro-esophageal reflux, and MUC4 was previously shown to be upregulated by several bile acids present in reflux. In this report, our aim was thus to determine whether MUC4 plays a role in biological properties of human esophageal cancer cells. For that stable MUC4-deficient cancer cell lines (shMUC4 cells) were established using a shRNA approach. In vitro (proliferation, migration and invasion) and in vivo (tumor growth following subcutaneous xenografts in SCID mice) biological properties of shMUC4 cells were analyzed. Our results show that shMUC4 cells were less proliferative, had decreased migration properties and did not express S100A4 protein when compared with MUC4 expressing cells. Absence of MUC4 did not impair shMUC4 invasiveness. Subcutaneous xenografts showed a significant decrease in tumor size when cells did not express MUC4. Altogether, these data indicate that MUC4 plays a key role in proliferative and migrating properties of esophageal cancer cells as well as is a tumor growth promoter. MUC4 mucin appears thus as a good therapeutic target to slow-down esophageal tumor progression.
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PMID:The MUC4 membrane-bound mucin regulates esophageal cancer cell proliferation and migration properties: Implication for S100A4 protein. 2188 95

The following on esophageal disease in pediatrics contains commentaries on acquisition of neuromuscular maturation; physiology of esophageal peristaltic and sphincteric reflexes; implications for clinical practice; and conditions that predispose to severe gastroesophageal reflux disease (GERD) in children with potential risk for esophageal cancer.
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PMID:Esophageal disease in pediatrics. 2195 Aug 32

Esophageal atresia (EA) affects one in 2,840 newborns, and over half have associated anomalies that typically affect the midline. After EA repair in infancy, gastroesophageal reflux (GER) and esophageal dysmotility and respiratory problems are common. Significant esophageal morbidity associated with EA extends into adulthood. Surgical complications, increasing age, and impaired esophageal motility predict the development of epithelial metaplasia after repair of EA. To date, worldwide, six cases of esophageal cancer have been reported in young adults treated for EA. According to our data, the statistical risk for esophageal cancer is not higher than 500-fold that of the general population. However, the overall cancer incidence among adults with repaired EA does not differ from that of the general population. Adults with repaired EA have had significantly more respiratory symptoms and infections, as well as more asthma and allergies than does the general population. Nearly half the patients have bronchial hyperresponsiveness. Thoracotomy-induced rib fusion and gastroesophageal reflux-associated columnar epithelial metaplasia are the most significant risk factors for the restrictive ventilatory defect that occurs in over half the patients. Over half the patients with repaired EA are likely to develop scoliosis. Risk for scoliosis is 13-fold after repair of EA in relation to that of the general population. Nearly half of the patients have had vertebral anomalies predominating in the cervical spine, and of these, most were vertebral fusions. The natural history of spinal deformities seems, however, rather benign, with spinal surgery rarely indicated.
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PMID:Long-term results of esophageal atresia: Helsinki experience and review of literature. 2196 Mar 12

The esophagus has a single rudimentary function of active transport of solids and liquids from the pharynx to the stomach and, rarely, venting of the stomach with retrograde passage of gastric contents into the pharynx. It is void of any digestive, absorptive, metabolic, or endocrine functions. Despite this simplicity of function, sex (biological and physiological characteristics, ie, male versus female) and gender (roles, behaviors, activities, and attributes that a given society considers appropriate, ie, man versus woman) differences exist in both normal esophageal function and esophageal disease. Some components of esophageal function are sex-dependent, and these differences must be considered in the interpretation of functional testing. In esophageal disease, particularly gastroesophageal reflux disease, Barrett esophagus, esophageal cancer, acquired immune deficiency syndrome, and scleroderma, there are sex and gender differences in the pathophysiology and response to treatment. Although discussions of treatment and outcomes might differ between the sexes and genders, there are no important data to support different care on the basis of sex or gender.
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PMID:The esophagus: do sex and gender matter? 2204 Oct 43

Aim. Reflux of duodenal contents can induce mucosal injury, stimulate cell proliferation, and promote tumorigenesis. We examined the expression of COX2 and p53 in rat esophageal lesions induced by duodenal content reflux. Methods. Thirty 8-week-old male Wistar rats were exposed to duodenal content esophageal reflux. All animals underwent an esophagoduodenal anastomosis (EDA) with total gastrectomy in order to produce chronic esophagitis. Ten rats were the sham. Control. They were sacrificed at the 40th week. Their esophagi were examined for HE, COX2, p53, and proliferating cell nuclear antigen (PCNA). Results. After 40 weeks of reflux, dysplasia, squamous cell carcinoma (SCC), and adenocarcinoma (ADC) were found. PCNA labeling index was higher in dysplastic and cancer tissue than that in normal. Overexpression of COX2 was shown in ADC and SCC. Wild-type p53 accumulation was found in ADC, and not in SCC. Conclusion. Reflux of duodenal contents into the esophagus led to ADC and SCC in rats. COX2 may play an important role in esophageal cancer by duodenal content reflux. Our present results suggest an association between wild-type p53 accumulation and COX2 expression in ADC, with no such relation seen in SCC.
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PMID:Expression of COX2 and p53 in Rat Esophageal Cancer Induced by Reflux of Duodenal Contents. 2227 78

Dyspepsia is the medical term for difficult digestion. It consists of various symptoms in the upper abdomen, such as fullness, discomfort, early satiation, bloating, heartburn, belching, nausea, vomiting, or pain. The prevalence of dyspepsia in the western world is approximately 20% to 25%. Dyspepsia can be divided into 2 main categories: "organic" and "functional dyspepsia" (FD). Organic causes of dyspepsia are peptic ulcer, gastroesophageal reflux disease, gastric or esophageal cancer, pancreatic or biliary disorders, intolerance to food or drugs, and other infectious or systemic diseases. Pathophysiological mechanisms underlying FD are delayed gastric emptying, impaired gastric accommodation to a meal, hypersensitivity to gastric distension, altered duodenal sensitivity to lipids or acids, altered antroduodenojenunal motility and gastric electrical rhythm, unsuppressed postprandial phasic contractility in the proximal stomach, and autonomic nervous system-central nervous system dysregulation. Pathogenetic factors in FD are genetic predisposition, infection from Helicobacter pylori or other organisms, inflammation, and psychosocial factors. Diagnostic evaluation of dyspepsia includes upper gastrointestinal endoscopy, abdominal ultrasonography, gastric emptying testing (scintigraphy, breath test, ultrasonography, or magnetic resonance imaging), and gastric accommodation evaluation (magnetic resonance imaging, ultrasound, single-photon emission computed tomography, and barostat). Antroduodenal manometry can be used for the assessment of the myoelectrical activity of the stomach, whereas sensory function can be evaluated with the barostat, tensostat, and satiety test. Management of FD includes general measures, acid-suppressive drugs, eradication of H. pylori, prokinetic agents, fundus-relaxing drugs, antidepressants, and psychological interventions. This review presents an update on the diagnosis of patients presenting with dyspepsia, with an emphasis on the pathophysiological and pathogenetic mechanisms of FD and the differential diagnosis with organic causes of dyspepsia. The management of uninvestigated and FD, as well as the established and new pharmaceutical agents, is also discussed.
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PMID:Dyspepsia: organic versus functional. 2232 2

Esophageal cancer is a common cancer worldwide and has a poor prognosis. The incidence of esophageal squamous cell cancer has been decreasing, whereas the incidence of esophageal adenocarcinoma has been increasing rapidly, particularly in Western men. Squamous cell cancer continues to be the major type of esophageal cancer in Asia, and the main risk factors include tobacco smoking, alcohol consumption, hot beverage drinking, and poor nutrition. In contrast, esophageal adenocarcinoma predominately affects the whites, and the risk factors include smoking, obesity, and gastroesophageal reflux disease. In addition, Asians and Caucasians may have different susceptibilities to esophageal cancer due to different heritage backgrounds. However, comparison studies between these two populations are limited and need to be addressed in the near future. Ethnic differences should be taken into account in preventive and clinical practices.
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PMID:Epidemiologic differences in esophageal cancer between Asian and Western populations. 2250 20

Gastroesophageal reflux disease is the most common esophageal disorder encountered in the United States. Gastroesophageal reflux disease symptoms are associated with a negative quality of life and increased healthcare costs and therefore require an effective management strategy. Although proton pump inhibitors remain the primary treatment of gastroesophageal reflux disease, they do not cure the disorder and can leave patients with persistent symptoms despite treatment. Moreover, patients are still at risk of developing such complications as peptic strictures, Barrett's metaplasia, and esophageal cancer. Although laparoscopic Nissen fundoplication has been the conventional alternative treatment for those patients who develop complications of gastroesophageal reflux disease, have intractable symptoms, or wish to discontinue taking proton pump inhibitors, investigators have persisted in developing a number of endoscopic approaches to the treatment of gastroesophageal reflux disease. The present report reviews the history of endoscopic treatments devised for the management of gastroesophageal reflux disease and explores the published data and outcomes associated with the latest approach-endoscopic fundoplication using the EsophyX2 device.
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PMID:Endoscopic management of gastroesophageal reflux disease: a review. 2251 18

In the last few decades, upper gastrointestinal endoscopy has become the most complementary test for investigation of esophageal diseases. Its accessibility and safety guarantee wide clinical utilization in patients with suspected benign and malignant diseases of the esophagus. Recent technological advances in endoscopic imaging and tissue analysis obtained from the esophagus have been useful to better understand and manage highly relevant diseases such as gastroesophageal reflux disease, eosinophilic esophagitis and esophageal cancer. Using endoscopy to elucidate esophageal disorders in children has been another field of intensive and challenging research. This editorial highlights the latest advances in the endoscopic management of esophageal diseases, and focuses on Barrett's esophagus, esophageal cancer, eosinophilic esophagitis, as well as esophageal disorders in the pediatric population.
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PMID:Update on endoscopic diagnosis, management and surveillance strategies of esophageal diseases. 2252 12

Although esophageal cancer (EC) is the eighth most common cancer in several European countries, it is one of deadliest worldwide. The most frequent predisposing factor implicated in its development is Barrett's esophagus (BE), an acquired metaplastic transformation of the esophageal lining cells from normal squamous epithelium into specialised or intestinal-like columnar epithelium. The major risk factor for BE is gastroesophageal reflux disease. Although BE is in itself a benign and often asymptomatic disorder, its clinical importance stems from the recognition that it represents the main precursor lesion for the development of esophageal adenocarcinoma (AC), a tumor that is rapidly increasing especially in developed countries and is associated with a low survival rate. This paper provides an overview of the epidemiology and natural history of BE as well as of the possible pathogenetic mechanisms underlying the development of BE and its progressive transition to AC. New diagnostic tests are described, recommendations for screening and surveillance are provided and surgical and ablative procedures to treat dysplastic lesions and early neoplasia are discussed. Claimed chemopreventive agents and biomarkers that in the near future may help identify people with a higher risk of EC are also considered.
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PMID:Barrett's esophagus and esophageal cancer: an overview. 2261 11


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