IL-8 is a proinflammatory cytokine that has been shown to promote the growth, angiogenesis and metastasis of colon cancer cells (8-11). Taken together, these observations suggest that S. bovis acts as a promoter of colorectal tumorigenesis. Later on in the mid-1970s, experiments with germ-free rats further showed that intestinal microflora played a modifying role in colorectal tumorigenesis. Germ-free rats developed much fewer colonic tumors compared to conventional rats when challenged with carcinogens (12,13). Since then, a number of commensal bacteria have been linked to CRC, selleck products including

Escherichia coli, Enterococcus faecalis, Bacteroides spp. (B. fragilis, B. vulgatus, Inhibitors,research,lifescience,medical B. stercoris), Eubacterium limosum, and Inhibitors,research,lifescience,medical Clostridium septicum (14-22). Ever since the oncogenic properties of H. pylori were firmly established in the stomach, studies on its oncogenicity have extended to other parts of the gastrointestinal tract, particularly the colon (23). To

date, the link between H. pylori infection and CRC remains inconclusive, with some reports showing an association (24-32) while others none (33-37). The results of two meta-analyses published Inhibitors,research,lifescience,medical in 2006 and 2008 both suggested a possible small increased risk of CRC in association with H. pylori infection (38,39). Several hypotheses have been proposed to explain the possible link between H. pylori infection and CRC. These include: (I) hypergastrinemia, (II) change in colorectal microflora, (III) toxin production, and (IV) chronic inflammation secondary to direct H. pylori colonization in the colon. Hypergastrinemia Gastrin and gastrin-like peptides received considerable attention in the 1980s and 1990s because of their growth-promoting Inhibitors,research,lifescience,medical properties. Early in vitro

studies demonstrated that gastrins had a direct mitogenic effect on cultured normal and neoplastic colonic cells (40-42). Later researches reported Inhibitors,research,lifescience,medical that induced hypergastrinemia resulted in hyperproliferation of colonic mucosa in transgenic mice (43-45). In addition, gastrin Entinostat gene knock-out mice showed decreased proliferation of the colonic mucosa (46). Furthermore, several case-control studies observed elevated serum/plasma gastrin levels in Tofacitinib JAK3 patients with colorectal adenomatous polyps and/or adenocarcinoma (47-50). These observations suggest that hypergastrinemia in the setting of H. pylori-associated atrophic gastritis promotes colorectal tumorigenesis. However, the link between hypergastrinemia and CRC has been in question from the beginning. Animal studies showed that drug-induced hypergastrinemia had no stimulatory effect on the growth of colonic mucosa or CRC progression (51-53). In fact, omeprazole was found to inhibit colorectal tumorigenesis induced by azoxymethane in rats despite causing hypergastrinaemia (54).