ESOPHAGEAL ADENOCARCINOGENESIS AND ITS PREVENTION

Project Details

Description

DESCRIPTION: The long-term goal of this project is to provide a mechanistic basis for the prevention of esophageal adenocarcinoma (EAC), a disease with a rapidly increasing incidence rate and a poor prognosis. For this purpose, the investigators have modified an esophagoduodenal anastomosis (EDA) model by giving iron supplements to rats. This model mimics human esophageal pathogenesis by causing chronic gastroduodenal-esophageal reflux and producing Barrett's esophagus (BE) and EAC, without the use of any carcinogen. Their hypothesis is that oxidative cellular damage, which is caused by reflux-induced inflammation, is a major factor driving the EAC pathogenic process, and thus preventable with the use of antioxidants and anti-inflammatory agents. They will test this hypothesis in the rat model and develop prevention approaches with the following specific aims: 1) To improve the nutritional status of the animals in their model and to investigate the effect of iron nutrition on oxidative cellular damage and the formation of BE/EAC. Rats (after surgery) will be maintained on an enriched AIN93 diet and supplemented with iron by different routes. Parameters reflecting inflammation and oxidative cellular damage and the formation of BE/EAC will be studied. 2) To test the hypothesis that oxidative stress is a major causative factor for the pathogenesis of EAC by studying its inhibition by antioxidative nutrients (agents). The effects of vitamin E, selenium, and N-acetylcysteine supplementation on oxidative damage parameters and their relationship with esophageal pathogenesis will be investigated. 3) To investigate the possible inhibition of BE/EAC formation by nonsteroidal anti-inflammatory drugs (NSAIDs). Sulindac, sulindac sulfone, and selective cyclooxygenase 2 (COX-2) inhibitors will be used to examine the roles of inflammation and COX-2 in esophageal adenocarcinogenesis. 4) To develop a model for studying the progression of esophageal metaplasia to adenocarcinoma and to study its inhibition by antioxidants and NASIDs.
StatusFinished
Effective start/end date4/1/981/31/09

Funding

  • National Institutes of Health: $275,212.00
  • National Institutes of Health: $248,733.00
  • National Institutes of Health: $255,578.00
  • National Institutes of Health: $283,432.00
  • National Institutes of Health: $290,253.00
  • National Institutes of Health: $290,253.00
  • National Institutes of Health
  • National Institutes of Health: $290,253.00
  • National Institutes of Health

ASJC

  • Medicine(all)

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