Prediction of nitric oxide concentrations during inflammation and carcinogenesis

Nitric oxide is a biological messenger which is synthesized enzymatically throughout the body and which has numerous physiological functions, including roles in blood pressure control, regulation of clotting, and neurotransmission. It is produced also by macrophages as part of the non-specific immune response, and has been shown to be toxic to invasive microorganisms. However, sustained overproduction of NO, as observed with chronic inflammation or infection, may damage the host tissue and has been linked to increased risk for cancer. Nitric oxide may facilitate tumorigenesis or metastasis by influencing tumor-cell proliferation, angiogenesis, or lymphangiogenesis. However, the concentrations of NO in inflamed tissues or during carcinogenesis are largely unknown. The objective of the research in this thesis was to predict NO concentrations in an inflamed colon and a cutaneous metastatic melanoma, two areas where NO has been implicated in the development or progression of disease. Nitric oxide production in the colon has been linked to inflammatory bowel disease (IBD) and increased risk for colon cancer. However, measurements of NO concentration in the inflamed colon have not been available and it is not known what levels of NO are pathophysiological. A computational model, based on anatomical length scales and rates of NO production measured in cell cultures, was developed to predict spatially varying NO concentrations within a colonic crypt under inflammatory conditions. A variety of scenarios were considered, including different spatial distributions of macrophages and a range of possible macrophage and epithelial synthesis rates for NO.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Chemical Engineering.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2010

Author dc:creator

• Chin, Melanie Pei-Heng

Advisor dc:contributor.advisor

• William M. Deen.

• Chemical Engineering.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/57866

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/57866