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David B. Schauer. Sohn, Jane Joo-hee, 1976- Massachusetts Institute of Technology. Biological Engineering Division. Massachusetts Institute of Technology. Department of Biological Engineering 2006-03-24T18:24:19Z 2006-03-24T18:24:19Z 2005 2005 http://hdl.handle.net/1721.1/30152 60523882 Thesis (Ph. D.)--Massachusetts Institute of Technology, Biological Engineering Division, 2005. Includes bibliographical references. Cancer is a leading cause of death in the world. Much work has been done to study the role of inflammation in carcinogenesis. One hypothesis suggests that inflammation causes oxidative stress that induces damage to cellular targets, including DNA. The multistep model of cancer proposes that cancer is a genetic disease in which mutations are required in carcinogenesis. When this theory was championed, research focused on somatic mutations. The focus has broadened to include epigenetic mechanisms in changing gene expression. The association between chronic infection, chronic inflammation and increased cancer risk has been supported by epidemiologic studies. Data link chronic inflammation associated with infectious disease to increased cancer risk. Some examples of such infectious agents include hepatitis B virus, Schistosoma haemotobium, and Helicobacter pylori. One objective of this thesis was to investigate the role of inflammation in self-limiting infection. Additional objectives focus on evaluating a novel model of intestinal and extraintestinal cancer, and using immune regulating cells as treatment for intestinal cancer. For the first objective, a murine mutational analysis model was used to study infection with Citrobacter rodentium, an enteric bacterium that causes self-limiting hyperplasia and inflammation. Increased mutant frequency was observed in association with elevated levels of iNOS 13 days post infection. The second aim, to characterize a novel model of neoplasia, led to the discovery of basosquamous cancer in mice with intestinal tumors. Finally, Apc-[Min] mice, a model of intestinal neoplasia, were treated with T regulatory cells to investigate the role of these cells on tumor development. These (cont.) cells were previously observed to have an anti-inflammatory and therapeutic effect on an infection-driven model of colon cancer. It was shown that T regulatory cells led to a decrease in the number of adenomas. In conclusion, it has been shown that self-limiting infection can increase mutant frequency. In addition, a novel model of intestinal and basosquamous cancer has been characterized, and a promising therapy for intestinal cancer has been validated. by Jane Joo-hee Sohn. Ph.D. 150 p. 7208757 bytes 7229026 bytes application/pdf application/pdf eng Massachusetts Institute of Technology MIT 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. http://dspace.mit.edu/handle/1721.1/7582 Biological Engineering Division. Intestinal cancer : linking infection, inflammation and neoplasia Thesis application/pdf false Publication unknown unknown <Publication xmlns="https://www.openaire.eu/cerif-profile/1.1/" id="786f72f7-9291-4052-9dec-3028c9b13abc"> <Type xmlns="https://www.openaire.eu/cerif-profile/vocab/COAR_Publication_Types">http://purl.org/coar/resource_type/c_1843</Type> <Language>eng</Language> <Title>Intestinal cancer : linking infection, inflammation and neoplasia</Title> <PublishedIn> <Publication> </Publication> </PublishedIn> <PublicationDate>2005</PublicationDate> <Authors> <Author> <DisplayName>Sohn, Jane Joo-hee, 1976-</DisplayName> <Affiliation> <OrgUnit> </OrgUnit> </Affiliation> </Author> </Authors> <Editors> </Editors> <Publishers> <Publisher> <DisplayName>Massachusetts Institute of Technology</DisplayName> <OrgUnit /> </Publisher> </Publishers> <License>http://dspace.mit.edu/handle/1721.1/7582</License> <Keyword>Biological Engineering Division.</Keyword> <Abstract>Cancer is a leading cause of death in the world. Much work has been done to study the role of inflammation in carcinogenesis. One hypothesis suggests that inflammation causes oxidative stress that induces damage to cellular targets, including DNA. The multistep model of cancer proposes that cancer is a genetic disease in which mutations are required in carcinogenesis. When this theory was championed, research focused on somatic mutations. The focus has broadened to include epigenetic mechanisms in changing gene expression. The association between chronic infection, chronic inflammation and increased cancer risk has been supported by epidemiologic studies. Data link chronic inflammation associated with infectious disease to increased cancer risk. Some examples of such infectious agents include hepatitis B virus, Schistosoma haemotobium, and Helicobacter pylori. One objective of this thesis was to investigate the role of inflammation in self-limiting infection. Additional objectives focus on evaluating a novel model of intestinal and extraintestinal cancer, and using immune regulating cells as treatment for intestinal cancer. For the first objective, a murine mutational analysis model was used to study infection with Citrobacter rodentium, an enteric bacterium that causes self-limiting hyperplasia and inflammation. Increased mutant frequency was observed in association with elevated levels of iNOS 13 days post infection. The second aim, to characterize a novel model of neoplasia, led to the discovery of basosquamous cancer in mice with intestinal tumors. Finally, Apc-[Min] mice, a model of intestinal neoplasia, were treated with T regulatory cells to investigate the role of these cells on tumor development. These</Abstract> <Abstract>(cont.) cells were previously observed to have an anti-inflammatory and therapeutic effect on an infection-driven model of colon cancer. It was shown that T regulatory cells led to a decrease in the number of adenomas. In conclusion, it has been shown that self-limiting infection can increase mutant frequency. In addition, a novel model of intestinal and basosquamous cancer has been characterized, and a promising therapy for intestinal cancer has been validated.</Abstract> <Access xmlns="http://purl.org/coar/access_right" > </Access> </Publication>