3-nitrotyrosine and Gastroesophageal-Reflux

The molecular and cellular mechanisms linking chronic inflammation and gastrointestinal malignancy are not known with certainty.. To investigate changes in potential causative factors during progression of esophagus cancer in a population living in high-risk area in Iran.. Formalin-fixed, paraffin-embedded esophageal specimens (n=87) from patients with gastroesophageal reflux disease (GERD), Barrett's metaplasia, adenocarcinoma (ADC) and squamous cells carcinoma (SCC) were collected based on their pathological diagnosis.. Immunohistochemical (IHC) technique was used to study tissue accumulation of P53, P21, cyclooxygenase-2 (COX-2), glutathione S-transferase-P (GST-Pi) and nitrotyrosine (NT) in patients and controls.. P53 expression was not detected in esophageal tissues from normal and GERD samples, whereas it was found positive in Barrett's, ADC, and SCC samples. P21 positive sample was relatively higher in ADC patients as compared to that in SCC (ADC: 52.6%; SCC: 25%). GST-Pi expression was equally accumulated in all the samples. NT was predominantly expressed in ADC (72.7%). COX-2 expression was significantly higher in Barrett's (60.0%) and ADC (66.6%) as compared to that in GERD, SCC and normal. These data were further confirmed by detecting the scores of immunostainings in all the positive samples.. The pathological changes in ADC and SCC samples which were associated with increasing frequency of NT and COX-2 provides further evidence for involvement of these inflammatory factors in progression of esophagus cancer.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Barrett Esophagus; Biomarkers, Tumor; Carcinoma, Squamous Cell; Case-Control Studies; Cyclin-Dependent Kinase Inhibitor p21; Cyclooxygenase 2; Disease Progression; Esophageal Neoplasms; Esophagus; Female; Gastroesophageal Reflux; Glutathione S-Transferase pi; Humans; Immunohistochemistry; Iran; Male; Middle Aged; Precancerous Conditions; Tumor Suppressor Protein p53; Tyrosine; Young Adult

Experimental studies suggest that free radicals are involved in acid and pepsin-induced damage of esophageal mucosa. The profile and balance between free radicals and antioxidant systems in human esophagitis are unknown.. Superoxide anion and its powerful oxidant reaction with nitric oxide (peroxynitrite) generation were determined in esophageal mucosal biopsies from 101 patients with different gastro-esophageal reflux diseases and 28 controls. Activity of both superoxide dismutase (SOD) and catalase, and reduced glutathione (GSH) levels, were also assessed. Expression of Cu, ZnSOD, MnSOD and tyrosine-nitrated MnSOD were analyzed by Western blot and/or immunohistochemistry.. The highest levels of superoxide anion generation were found in patients with severe lesions of esophagitis. Peroxynitrite generation was intense in Barrett's biopsies, weaker in esophagitis and absent/weak in normal mucosa. Expression of Cu, ZnSOD and MnSOD isoforms were present in normal mucosa and increased according to the severity of the lesion, reaching the highest level in Barrett's esophagus. However, SOD mucosal activity significantly decreased in patients with esophagitis and Barrett's esophagus, which was, at least in part, due to nitration of its tyrosine residues. Catalase activity and GSH levels were significantly increased in mucosal specimens from patients with esophagitis and/or Barrett's esophagus.. A decrease in SOD antioxidant activity leading to increased mucosal levels of superoxide anion and peroxynitrite radicals may contribute to the development of esophageal damage and Barrett's esophagus in patients with gastroesophageal reflux. Administration of SOD may be a therapeutic target in the treatment of patients with esophagitis and Barrett's esophagus.

Topics: Adult; Aged; Aged, 80 and over; Barrett Esophagus; Esophagitis; Female; Free Radicals; Gastroesophageal Reflux; Glutathione; Humans; Male; Middle Aged; Oxidoreductases; Reactive Oxygen Species; Superoxide Dismutase; Tyrosine