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)

Abnormal gastro-oesophageal reflux and bile acids have been linked to the presence of Barrett's oesophageal premalignant lesion associated with an increase in mucin-producing goblet cells and MUC4 mucin gene overexpression. However, the molecular mechanisms underlying the regulation of MUC4 by bile acids are unknown. Since total bile is a complex mixture, we undertook to identify which bile acids are responsible for MUC4 up-regulation by using a wide panel of bile acids and their conjugates. MUC4 apomucin expression was studied by immunohistochemistry both in patient biopsies and OE33 oesophageal cancer cell line. MUC4 mRNA levels and promoter regulation were studied by reverse transcriptase-PCR and transient transfection assays respectively. We show that among the bile acids tested, taurocholic, taurodeoxycholic, taurochenodeoxycholic and glycocholic acids and sodium glycocholate are strong activators of MUC4 expression and that this regulation occurs at the transcriptional level. By using specific pharmacological inhibitors of mitogen-activated protein kinase, phosphatidylinositol 3-kinase, protein kinase A and protein kinase C, we demonstrate that bile acid-mediated up-regulation of MUC4 is promoter-specific and mainly involves activation of phosphatidylinositol 3-kinase. This new mechanism of regulation of MUC4 mucin gene points out an important role for bile acids as key molecules in targeting MUC4 overexpression in early stages of oesophageal carcinogenesis.
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PMID:Transcriptional regulation of human mucin MUC4 by bile acids in oesophageal cancer cells is promoter-dependent and involves activation of the phosphatidylinositol 3-kinase signalling pathway. 1458 90

We reviewed our experience on tracheomalacia (TM) and bronchomalacia (BM) in children who presented with chronic respiratory problems and evaluated their clinical and radiologic characteristics and their associations with other disorders. There were 26 males and 8 females with a median age of 9 months. The main symptoms were wheezing, persistent or recurrent pneumonia, and chronic cough. Atelectasis on chest radiograph was the most common sign. Of 23 children with TM, 1 had a double aortic arch, 1 had tracheoesophageal fistula, and 1 other had associated laryngomalacia. BM was found in 27 children and was predominantly seen on the right side. TBM was found in 16 cases (in an infant TBM was accompanied by pharyngeal dyskinesia and in another by laryngomalacia). Malacia disorders were associated with gastroesophageal reflux, cardiovascular anomalies, and tracheoeosophageal fistula. TM and BM should be considered in the differential diagnosis of children with chronic and recurrent respiratory symptoms. Early diagnosis of malacia disorders will prevent unnecessary use of antibiotics or antiasthmatic drugs, which are often abused to treat these children. In these patients, treatment for associated diseases should also be considered.
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PMID:Tracheomalacia and bronchomalacia in 34 children: clinical and radiologic profiles and associations with other diseases. 1632 64

Dissemination of gastric cancer may usually occur by direct spread through the perigastric tissues to adjacent organ, lymphatic spread, and hematogenous spread. We report a rare case of gastric cancer with mucosal metastastic lesion on the upper esophagus that was diagnosed by endoscopy and endosonography. A biopsy of the esophageal mass was performed and the pathologic findings with immunohistochemical stain for Mucin-5AC are proved to be identical to that of gastric adenocarcinoma, suggesting metastasis from main lesion of the gastric cancer. The lesion could not be explained by lymphatic or hematogenous spread, and its metastasis mechanism is considered to be different from previous studies. We suggest that the gastroesophageal reflux of cancer cells could be one of the possible metastatic pathways for metastasis of esophagus from an adenocarcinoma of the stomach.
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PMID:Esophageal mucosal metastasis from adenocarcinoma of the distal stomach. 2380 75