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. ? ?

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-GMA-2 (01))
Program Officer
Hamilton, Frank A
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Medicine & Dentistry of NJ
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
Michigami, Yuki; Watari, Jiro; Ito, Chiyomi et al. (2017) Effects of long-term aspirin use on molecular alterations in precancerous gastric mucosa in patients with and without gastric cancer. Sci Rep 7:13384
Kawanaka, Maki; Watari, Jiro; Kamiya, Noriko et al. (2016) Effects of Helicobacter pylori eradication on the development of metachronous gastric cancer after endoscopic treatment: analysis of molecular alterations by a randomised controlled trial. Br J Cancer 114:21-9
Fukui, Shota; Watari, Jiro; Tomita, Toshihiko et al. (2016) Localization of specialized intestinal metaplasia and the molecular alterations in Barrett esophagus in a Japanese population: an analysis of biopsy samples based on the ""Seattle"" biopsy protocol. Hum Pathol 51:32-40
Das, Koushik K; Xiao, Hong; Geng, Xin et al. (2014) mAb Das-1 is specific for high-risk and malignant intraductal papillary mucinous neoplasm (IPMN). Gut 63:1626-34
Watari, Jiro; Chen, Nancy; Amenta, Peter S et al. (2014) Helicobacter pylori associated chronic gastritis, clinical syndromes, precancerous lesions, and pathogenesis of gastric cancer development. World J Gastroenterol 20:5461-73
Watari, Jiro; Moriichi, Kentaro; Tanabe, Hiroki et al. (2012) Biomarkers predicting development of metachronous gastric cancer after endoscopic resection: an analysis of molecular pathology of Helicobacter pylori eradication. Int J Cancer 130:2349-58
Das, Kiron M; Kong, Yingxin; Bajpai, Manisha et al. (2011) Transformation of benign Barrett's epithelium by repeated acid and bile exposure over 65 weeks: a novel in vitro model. Int J Cancer 128:274-82
Watari, Jiro; Moriichi, Kentaro; Tanabe, Hiroki et al. (2009) Differences in genetic instability and cellular phenotype among Barrett's, cardiac, and gastric intestinal metaplasia in a Japanese population with Helicobacter pylori. Histopathology 55:261-9
Das, Koushik K; Bajpai, Manisha; Kong, Yingxin et al. (2009) Mesalamine suppresses the expression of TC22, a novel tropomyosin isoform associated with colonic neoplasia. Mol Pharmacol 76:183-91
Moriichi, Kentaro; Watari, Jiro; Das, Kiron M et al. (2009) Effects of Helicobacter pylori infection on genetic instability, the aberrant CpG island methylation status and the cellular phenotype in Barrett's esophagus in a Japanese population. Int J Cancer 124:1263-9

Showing the most recent 10 out of 15 publications