bovis/gallolyticus were found in proliferative lesions, 15% of cancers and 21% of adenomas. A recent study

done by our team supported this concept [39] showing that the level of S. bovis/gallolyticus IgG antibodies in adenoma patients was higher than in colorectal cancer patients or control subjects. However, Burns et al. [75] did not get the same findings; they found that the incidence of S. bovis/gallolyticus carriage in all colons with polyps was intermediary between normal colons and colons with carcinoma; however, the difference did not achieve statistical significance. Since there is evidence that colon cancer progresses from normal tissue to adenoma and then to carcinoma through an accumulation of genetic alterations BTK inhibitor in vitro [80], DMXAA the remarkable association between S. bovis/gallolyticus and adenomatous polyps seems to be of importance. Although ulceration

of neoplastic lesions might form a pathway for S. bovis/gallolyticus to enter the bloodstream [7], the association of S. bovis/gallolyticus bacteremia with non-ulcerated colonic polyps indicates an etiological/promoter role of S. bovis/gallolyticus in polyps progression [81, 82]. Therefore, the possibility of S. bovis/gallolyticus to act as a promoter for the preneoplastic lesions worths consideration. Ellmerich et al. [37] supported this hypothesis. They treated normal rats with S. bovis wall MRT67307 molecular weight extracted antigens; rats did not develop hyperplastic colonic crypts; however, 50% of rats, that already received a chemocarcinogen, developed neoplastic lesions upon receiving S. bovis wall extracted antigens. This indicated that S. bovis/gallolyticus might exert their carcinogenic

activity in colonic mucosa when preneoplastic lesions are established. Therefore, the role of S. bovis/gallolyticus in the etiology and/or acceleration of the transformation of aberrant crypts to adenoma and to a cancer is being considered. Accordingly, the knowledge of S. bovis/gallolyticus association with adenoma of colorectal mucosa has important clinical implications. If colorectal lesions could be discovered at an early Carnitine palmitoyltransferase II stage, curative resection might become possible [83]. Thus, bacteremia due to S. bovis/gallolyticus should prompt rigorous investigation to exclude both endocarditis and tumors of the large bowel [82, 84]. Therefore, it was concluded that the discovery of a premalignant proliferative lesion in patients with history of bacteremia/endocarditis justifies the exploration of the colon by barium enema and/or colonoscopy [82, 84]. Etiological versus non-etiological role of S. bovis/gallolyticus in the development of colorectal tumors The underlying mechanisms for the association of S. bovis/gallolyticus bacteremia/endocarditis with colorectal tumors have long been obscure. The possible reason behind that, maybe, S. bovis/gallolyticus is a member of intestinal flora in 2.5 to 15% of individuals; this usually leads scientists to counteract the malicious role of this bacteria [44, 75].