The overall hypothesis for this proposal is that metaplastic epithelium at the distal esophagus is an intestinal metaplasia of colonic phenotype, and the process may lead to specialized columnar epithelium (SCE), or Barrett's epithelium (BE), due to various environmental factors. We developed a novel monoclonal antibody (mAb) 7E12H12 IgM isotype, also known as mAb Das-1, that specifically reacts with normal colon epithelium, but not with any other parts of the gastrointestinal tract. However, we reported that it reacts with SCE and adenocarcinoma arising from SCE with 100% specificity. Preliminary studies also demonstrate that """"""""cardiac type"""""""" of epithelium at the esophago-gastric (E-G) junction reacts with mAb Das-1. Using biopsy specimens from E-G junction and mAb Das-1, by immunoperoxidase assay (IPA), we will determine the frequency of intestinal metaplasia at the distal esophagus (IM-DE) reactive to mAb Das-1 without histological evidence of SCE. The relationship of IM-DE to history of gastroesophageal reflux disorder, age, sex and ethnic background and use of anti-secretory drugs, such as H2-blockers and proton pump inhibitors (PPI) will be evaluated. We will further examine if patients with IM-DE eventually develop SCE over 2 to 4 years of follow-up studies. Reversibility of this metaplastic process will be examined by early """"""""chemoprevention"""""""" using PPI in patients who display IM-DE without histological evidence of SCE. To investigate if mAb Das-1 is a better predictor than histology, the presence of the immunoreactivity and parallel histology will be utilized to monitor eradication and recurrence of BE following ablative therapies. Colon epithelial protein-epitope (CEP), recognized by mAb Das-1 will be ultrastructurally localized by immunoelectronmicroscopy and confocal microscopy. Biochemical and molecular studies will utilize characterization of CEP, change in the expression of CEP following exposure of BE cell lines to various environmental factors such as acid pH, and proinflammatory cytokines and cloning of CEP gene. ? ?
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