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)

Deep esophageal glands play a vital role in the protection and regeneration of the esophageal mucosa. Conditions such as gastroesophageal reflux disease and Barrett's esophagus have been associated with a change in the usual glands by oncocytic metaplasia. However, little is known regarding the function of oncocytes or the relevance of this metaplastic change in the human esophagus. We hypothesized that oncocytes of deep esophageal glands also express markers characteristic of a ductal epithelial phenotype because similar oncocytes have been described as part of large ductal epithelial cells in salivary glands. We used immunohistochemical stains to define structural, functional, proliferative, and potential stem/progenitor characteristics of oncocytes. Oncocytes did not express mucins or lysozyme C, two molecules found in mucous cells and used for antimicrobial defense. Oncocytes did not express CK5, a cytokeratin found in myoepithelial cells and basal epithelial cells, but expressed CK7, a cytokeratin found in intralobular ductal epithelial cells and luminal epithelial cells of the main duct. Oncocytes expressed cystic fibrosis transmembrane conductance regulator and sodium/potassium ATPase, ion channels that play a role in bicarbonate secretion. Membrane-bound beta-catenin was detected in oncocytes, but these cells did not express the proliferative marker Ki67. Approximately, a third of oncocytes expressed SOX9 and p63, transcription factors expressed in epithelial progenitor cells in multiple organs. Moreover, oncocytes expressed CD44, a transmembrane Glycoprotein expressed in cancer stem cells. Taken together, our data show that oncocytes express markers of intralobular ductal epithelial cells and luminal epithelial cells of the main duct. Additionally, our observations suggest that oncocytes act as epithelial progenitor cells and play a role in bicarbonate secretion. Since oncocytic metaplasia is associated with conditions of chronic acid injury, it is possible that oncocytes replace the mucous cells in deep esophageal glands (dEG) as an adaptive change to counteract injury from acid reflux. The marker characterization suggests that oncocytes may originate from transdifferentiation of myoepithelial and mucous cells. This transdifferentiation might lead to an overall decrease of mucins production and secretion by the dEG and a subsequent reduction of the protection conferred by the viscoelastic mucous layer.
...
PMID:Characterization of oncocytes in deep esophageal glands. 2624 38

Despite being the largest part of the human gastrointestinal (GI) tract, the small intestine accounts for only 1-1.4% of all GI malignancies. Adenocarcinoma is the most common primary small bowel malignancy, with the most common site being the duodenum. On the other hand, squamous cell carcinoma (SCC) of the duodenum is extremely uncommon. We report the first case of mixed adenocarcinoma and SCC occurring in the third part of duodenum (D3). Our patient, a 64-year-old female with history of GERD, hypertension, and IDDM presented with 4 weeks of nausea, vomiting, and abdominal pain. Tomographic imaging of her abdomen demonstrated a distended stomach and a proximal duodenum with narrow caliber changes at the level of D3. An EGD revealed a tight stricture at D3 that could not be traversed. Stricture biopsies revealed duodenal mucosa with two small foci of SCC (positive for p63 and CK5/6) and adenocarcinoma (positive for CK7 and Moc31). Peritoneal metastases were detected on exploratory laparotomy, making the tumor surgically incurable. As she progressively declined and with worsening liver enzymes and general debility, she was not a candidate for chemotherapy and was eventually discharged on home hospice. Small bowel SCC/adenocarcinoma is an exceedingly uncommon cancer, making further case reports such as ours important to understand the nature of this entity and establish management guidelines.
 ...
PMID:Mixed Adenocarcinoma and Squamous Cell Carcinoma of Duodenum: A Case Report and Review of the Literature. 2887 13