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Protective effects of dietary and pharmaceutical agents against gastroesophageal reflux induced esophageal cancer
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Title
Protective effects of dietary and pharmaceutical agents against gastroesophageal reflux induced esophageal cancer
Name
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Hao
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Jing
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Jing Hao
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author
Name
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Yang
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Chung S.
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Advisory Committee
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Chung S. Yang
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chair
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Reuhl
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Kenneth R.
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Advisory Committee
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Kenneth R. Reuhl
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internal member
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Suh
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Nanjoo
Affiliation
Advisory Committee
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Nanjoo Suh
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internal member
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Thomas
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Paul
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Advisory Committee
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Paul Thomas
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(authority = RULIB)
internal member
Name
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Chen
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Xiaoxin
Affiliation
Advisory Committee
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Xiaoxin Chen
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outside member
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Rutgers University
Role
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degree grantor
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Graduate School - New Brunswick
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school
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Text
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theses
OriginInfo
DateCreated
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2008
DateOther
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2008-10
Language
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English
PhysicalDescription
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electronic
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application/pdf
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text/xml
Extent
xvii, 138 pages
Abstract
There 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.
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.
Note
(type = degree)
Ph.D.
Note
(type = bibliography)
Includes bibliographical references (p. 115-136).
Subject
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Topic
Toxicology
Subject
(ID = SUBJ2);
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Topic
Esophagus--Cancer--Treatment
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TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier
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rucore19991600001
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http://hdl.rutgers.edu/1782.2/rucore10001600001.ETD.17487
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ETD_1203
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Identifier
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doi:10.7282/T3HX1D1V
Genre
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ETD doctoral
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The author owns the copyright to this work.
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Copyright protected
Availability
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Open
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JING HAO
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Copyright holder
Affiliation
Rutgers University. Graduate School - New Brunswick
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Non-exclusive ETD license
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Author Agreement License
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I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
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