Uniform TitleProtective effects of dietary and pharmaceutical agents against gastroesophageal reflux induced esophageal cancer
NameHao, Jing (author), Yang, Chung S. (chair), Reuhl, Kenneth R. (internal member), Suh, Nanjoo (internal member), Thomas, Paul (internal member), Chen, Xiaoxin (outside member), Rutgers University, Graduate School - New Brunswick,
DescriptionThere are two primary goals of this study. One is to establish a mouse esophageal adenocarcinoma (EAC) model and the other is to develop chemopreventive strategies to prevent EAC. We performed esophagogastroduodenal anastomosis (EGDA) on wild-type, p53A135V transgenic, and INK4a/Arf+/- mice of A/J strain. Wild-type mice with EGDA were also treated with iron (50 mg/kg/m, i.p.) or gastrectomy plus iron to enhance carcinogenesis. At week 20 and week 40, we observed metaplasia in wild-type mice (1/20 at week 20; 6/37 at week 40), p53A135V mice (1/19 at week 20; 2/42 at week 40) and wild-type mice that also receiving gastrectomy and iron (1/15 at week 40). Esophageal squamous cell carcinoma (ESCC) developed in INK4a/Arf+/- mice (1/14) and wild-type mice receiving gastrectomy and iron (3/14) at week 40. Twelve (92.3%) wild-type EGDA mice which were given iron from week 40 to 80 developed ESCC at week 80. None of these mice developed Barrett's esophagus (BE) or EAC.
We investigated the possible chemopreventive effects of α-tocopherol (389 ppm and 778 ppm), N-acetylcysteine (NAC, 500 ppm and 1,000 ppm), their combination (389 ppm α-tocopherol and 500 ppm NAC), omeprazole (1,400 ppm), Licofelone (1,000 ppm), the combination of omeprazole (250 ppm) and celecoxib (500 ppm) and the combination of zileuton (1,000 ppm) and celecoxib (500 ppm) in our EGDA rat model. All the esophagi of rats were harvested for histopathological examination. α-Tocopherol dose-dependently decreased the incidence of EAC. The combination of α-tocopherol 389 ppm and NAC 500 ppm significantly reduced the incidence of EAC. Both omeprazole and Licofelone did not show inhibitory effect at the dose given. The combination of zileuton and celecoxib significantly reduced the tumor incidence, while omeprazole in combination with celecoxib did not show any effect on tumor incidence.
We concluded that under gastroesophageal reflux A/J mice are prone to develop ESCC but not EAC. α-Tocopherol can inhibit the development of EAC in our EGDA model with rats and stronger effects can be achieved when used in combination with NAC. Licofelone, omeprazole and omeprazole in combination with celecoxib did not show any chemopreventive effect on our EGDA rat model.
NoteIncludes bibliographical references (p. 115-136).
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.