Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0546837 (esophageal cancer)
 8,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Asymmetric dialkylnitrosamines induce esophageal cancer in rats and hence might be involved in the etiology of this cancer in humans. As a test of this hypothesis, we examined whether nitrosamines can be activated by segments of human esophagus and by microsomes of human and rat esophagus and liver. Specimens of 8 human esophagi were removed less than 6 h after death, and segments were incubated for 6 h with 23 and 300 microM N-nitrosomethyl-n-amylamine (NMAA). Hydroxy-NMAA yields were determined by gas chromatography-thermal energy analysis and were insignificant except for those of 5-hydroxy-NMAA, which were low. Microsomes were prepared from 4 batches of human esophagi and samples with 0.6 mg protein were incubated for 20 min with NMAA and cytochrome P-450 cofactors. We determined hydroxy-NMAAs as before and aldehydes by high-performance liquid chromatography of their 2,4-dinitrophenylhydrazones. Incubation of these microsomes with 12 mM NMAA yielded mean values of 0.64 nmol formaldehyde ("demethylation"), 0.21 nmol pentaldehyde ("depentylation"), and 0.56 nmol total hydroxy-NMAAs/min/mg protein. Metabolite yields under various conditions were determined, including a demonstration that carbon monoxide inhibited 81% of NMAA demethylation, indicating that cytochrome P-450 enzymes were involved. We also examined N-nitrosodimethylamine (NDMA) demethylation by the same microsomes. Rat esophageal microsomes dealkylated NMAA and NDMA similarly to human esophageal microsomes, but with 2-6 times and twice the activity, respectively. Human and rat esophageal microsomes demethylated 6 mM NMAA 18-20 times as rapidly as they demethylated 5 mM NDMA, in contrast to liver microsomes of these species, which demethylated 6 mM NMAA only 0.9-1.4 times as rapidly as they demethylated 5 mM NDMA. However, liver microsomes of both species were more active than esophageal microsomes for NMAA depentylation. The occurrence of NMAA demethylation and (to a lesser extent) depentylation with both human and rat esophageal microsomes is important because these are the activating reactions, and suggests that both human and rat esophagus contain P-450 isozymes that specifically dealkylate asymmetric dialkylnitrosamines.
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PMID:Metabolism of N-nitrosomethyl-n-amylamine by microsomes from human and rat esophagus. 161 24

Esophageal cancer is treated optimally with a combined-modality approach according to most clinical investigators. Cytotoxic chemotherapy and ionizing radiotherapy, given in a concomitant schedule, has yielded superior survival rates compared with radiotherapy alone. However, mucosal toxicity from such treatment may compromise quality of life and may mandate an unscheduled break in therapy in some patients who do not respond readily to standard treatments such as antacids; combinations of viscous xylocaine, aluminum hydroxide-magnesium carbonate, and diphenhydramine hydrochloride; oral liquid morphine sulfate, hydrocodone bitartrate, or acetaminophen. Hence, a number of alternative strategies that are designed to either prevent or limit toxicity to normal tissues without diminishing the antitumor effect are being tested. These include the use of conformal radiotherapy treatment planning techniques, amifostine (Ethyol, WR-2721), gene therapy via intratumoral injection of manganese superoxide dismutase-plasmid/liposome, glutamine, melatonin, omega-3-polyunsaturated fatty acids, transforming growth factor, flavonoid compounds, probucol, and keratinizing growth factor. An ongoing phase 2 trial by the North Central Cancer Treatment Group (NCCTG) may help clarify a role for cytoprotectants in patients receiving combined-modality therapy for esophageal cancer.
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PMID:Esophageal cancer and the esophagus: challenges and potential strategies for selective cytoprotection of the tumor-bearing organ during cancer treatment. 1191 87

Acute poisonings with corrosive substances may cause serious chemical injuries to upper gastrointestinal tract, the most common location being the esophagus and the stomach. If the patient survives the acute phase of the poisoning, regenerative response may result in esophageal and/or gastric stenosis and increased risk for esophageal cancer. Acute corrosive intoxications pose a major problem in clinical toxicology since the most commonly affected population are the young with psychic disorders, suicidal intent and alcohol addiction. In establishing the diagnosis of acute corrosive poisonings, the severity of the post-corrosive endoscopic changes of the esophagus, stomach and duodenum is of major importance. According to Holinder and Fridman classification, post-corrosive endoscopic changes are classified in three degrees: First degree--superficial damage associated with hyperthermia, epithelial desquamation and mucous edema. Second degree--transmucous damage affecting all of the mucosal layers, followed by exudation, erosions and ulcerations. Third degree--transmural damage associated with ulcer's penetration in the deep layers of the tissue and neighboring organs. Severity of the lesions depends on the nature, quantity and concentration of the corrosive substance, the duration of exposure and current state of the exposed organs. Most often caustic injuries occur to the esophagus and stomach since the corrosive substance remains there for a longer period of time. Treatment of the acute corrosive intoxications include: neutralization of corrosive agents, antibiotics, corticosteroids, anti-secretory therapy, nutritional support, collagen synthesis inhibitors, esophageal dilation and stent placement, and surgery. The most common complications that may appear are: perforation, gastrointestinal bleeding, sepsis, esophageal strictures and stenosis, stenosis of gastric antrum and pylorus, cancer of the esophagus and the stomach. Today, owing to the substantially enhanced diagnostic and therapeutic approach, the mortality percentage has been reduced from 20% to 1-5%. Women more often than men are intoxicated with corrosive substances; suicidal poisonings prevail; the most abused agents are hydrochloric acid (HCl) and sodium hydroxide; intoxications are more common in children (80% out of the total number of intoxications). In spite of the preventive measures for restriction of the trade with corrosive substances, standardization of their concentration and protective safety bottle caps, still the number of corrosive intoxications, the percentage of post-corrosive complications and the handicap are high. Acute corrosive intoxications are the leading cause of death in clinical toxicology.
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PMID:Post-corrosive injuries of upper gastrointestinal tract. 2069 48

A 69-year-old man was admitted to the emergency department 3 hours after ingestion of a bleaching agent containing hypochlorous acid and sodium hydroxide in a suicide attempt. Enhanced chest computed tomography scans taken on admission indicated an edematous esophagus and air bubbles in the mediastinum. He underwent endotracheal intubation and mechanical ventilation until day 9 because of laryngeal edema. On day 10, his endoscopy indicated diffuse reddish mucosal hyperemia, erosions, and lacerated mucosal lesions in the esophagus that were indicative of grade 2b corrosive esophagitis. Treatment with a proton pump inhibitor was initiated, with which the condition of the esophagus improved, and on day 44, a slight stricture of the upper part of the esophagus was observed. He was discharged on day 64 without any complaints. The ingestion of sodium hypochlorite induces corrosive esophagitis and acute phase of gastritis. Ingestion of any corrosive agent is known as a risk factor for esophagus cancer in the long-term. In such cases with esophageal stricture, esophagectomy is recommended for preventing esophagus cancer. Considering the age of the patient, however, he did not undergo esophagectomy.
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PMID:[Conservative treatment improved corrosive esophagitis and pneumomediastinum in a patient who ingested bleaching agent containing sodium hypochlorite and sodium hydroxide]. 2472 60