Thesis (Ph.D.) - University of St Andrews, February 2009. / Restricted until 23rd February 2012.

In this study, we sought to define an underlying molecular mechanism of how inflammation induces cancer initiation. Cancer-associated inflammation is marked by the presence of inflammatory cells and mediators including cytokines, chemokines, and reactive oxygen species. There is a growing body of evidence establishing the link between chronic inflammation and cancer. Twenty percent of cancers have been linked to chronic infections. For instance, bacterial and viral infections induce inflammation which is a known risk factor for cancer. During inflammation, Ml macrophages' production of pro-inflammatory cytokines and reactive oxygen species (ROS) drives their function as anti-microbial. Likewise, the transcription factor nuclear factor kappa B (NF-KB) is known to induce a variety of stimulators, including ROS, to contribute to the inflammatory process. Therefore, we sought to explore the relationship between Ml macrophages and NF-KB, suggesting that Ml macrophage mediates cancer initiation via a NF-KB-dependent pathway, which collectively contributes to a metastatic phenotype.