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dc.contributor.advisorJames G. Fox.en_US
dc.contributor.authorLee, Chung-Wei, Ph. D. Massachusetts Institute of Technologyen_US
dc.contributor.otherMassachusetts Institute of Technology. Biological Engineering Division.en_US
dc.date.accessioned2009-01-23T14:52:08Z
dc.date.available2009-01-23T14:52:08Z
dc.date.copyright2007en_US
dc.date.issued2007en_US
dc.identifier.urihttp://dspace.mit.edu/handle/1721.1/39909en_US
dc.identifier.urihttp://hdl.handle.net/1721.1/39909
dc.descriptionThesis (Ph. D.)--Massachusetts Institute of Technology, Biological Engineering Division, 2007.en_US
dc.descriptionLeaf 187 blank.en_US
dc.descriptionIncludes bibliographical references.en_US
dc.description.abstractGastric cancer is the second most common malignancy in the digestive system and the second leading cause of cancer-related death worldwide. Epidemiological data and experimental studies have identified several risk factors for gastric cancer, including Helicobacter pylori infection, low fruit and vegetable intake, N-nitrosoamine exposure, high salt diet, and smoking. Among these risk factors, H. pylori infection is the major cause of gastric cancer. Therefore, H. pylori has been classified as a type 1 (definite) carcinogen for gastric cancer by the World Health Organization (WHO) in 1994. H. pylori colonizes the human stomach and has been definitively linked to chronic gastritis. Infection in some: susceptible individuals results in serious gastric disease such as peptic ulcer or gastric cancer. The first aim of this thesis was to examine the role of different T cell subpopulations in H. pylori gastritis. Using a murine adoptive transfer model, adoptive transfer of wildtype (wt) effector T cells (TE) into H. pylori-infected lymphopenic Rag2-/- recipient mice resulted in H. pylori-associated corpus gastritis superimposed with non-specific gastroduodenitis. Cotransfer with TE and regulatory T cells (TR) from wt or IL10-/- mice reduced gastroduodenitis, but only wt TR cells reduced corpus gastritis.en_US
dc.description.abstract(cont.) The second aim of this thesis was to evaluate the effect of vitamin C on H. pylori gastritis in vitamin C-deficient gulo-/- mice. It was found that a high vitamin C supplementation (3300 mg/L) in drinking water did not protect H. pylori gastritis, while a low vitamin C supplementation (33 mg/L) reduced the severity of H. pylori gastritis via an attenuated cellular immune response to H. pylori. The third aim of this thesis was to examine the role of DNA repair in H. pylori-associated gastric disease. We found that H. pylori-associated premalignant gastric atrophy was more severe in infected mice lacking DNA repair protein 3-alkyladenine DNA glycosylase or 06-methylguanine DNA methyltransferase in comparison to infected wt control mice. The forth aim of this thesis was to examine whether antimicrobial H. pylori eradication therapy could prevent gastric cancer development in INS-GAS mice, a model of gastric cancer. We found that antimicrobial H. pylori eradication therapy prevented the progression to gastric cancer in H. pylori-infected INS-GAS mice when treatment was instituted at an early stage of H. pylori infection.en_US
dc.description.abstract(cont.) In conclusion, these studies provide further insight into the role of host immune responses in H. pylori pathogenesis. Additionally, information was garnered regarding the roles of vitamin C supplementation, DNA repair proteins, and H. pylori eradication therapy in H. pylori-associated gastric disease using genetically manipulated mice.en_US
dc.description.statementofresponsibilityby Chung-Wei Lee.en_US
dc.format.extent187 leavesen_US
dc.language.isoengen_US
dc.publisherMassachusetts Institute of Technologyen_US
dc.rightsMIT theses are protected by copyright. They may be viewed, downloaded, or printed from this source but further reproduction or distribution in any format is prohibited without written permission.en_US
dc.rights.urihttp://dspace.mit.edu/handle/1721.1/39909en_US
dc.rights.urihttp://dspace.mit.edu/handle/1721.1/7582en_US
dc.subjectBiological Engineering Division.en_US
dc.titlePathogenesis of the carcinogenic bacterium, Helicobacter pylorien_US
dc.typeThesisen_US
dc.description.degreePh.D.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biological Engineering
dc.identifier.oclc182574790en_US


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