On the other hand, the production of angiogenic LY2606368 factors in colonic

mucosa, such as IL-8, which can be triggered by S. bovis/gallolyticus antigens, may also favor the progression of colon carcinogenesis [39, 40, 89, 99, 100] (Figure 1). This resembles H. pylori infection for the development of chronic inflammation in the gastric mucosa [101]. Therefore, chronic infection and subsequent chronic inflammation seem responsible for the maintenance and development of pre-existing neoplastic lesions [39, 40, 102]. Figure 1 Illustration for the discovered and suggested mechanisms underlying the etiological association of S. bovis/gallolyticus (SBG) bacteria with promoting, propagating, or initiating colorectal tumors, bacteremia, and endocarditis. Moreover, it was found that wall extracted antigens of S. bovis induced in vitro overexpression of cyclooxygenase-2

(COX-2) [38, 96]. COX-2, Niraparib research buy via prostaglandins, promotes cellular proliferation and angiogenesis and inhibits apoptosis (Figure 1); thus it acts as a promoter in cancer pathway [103]. It is noteworthy to mention that non-steroidal anti-inflammatory drugs decrease the relative risk of gastrointestinal carcinomas through inhibiting the activity of COX-2 which is over-expressed in up to 85% of colorectal adenocarcinomas [104]. Alike, Haqqani et al., [105] revealed that the activation of INCB028050 in vitro leukocytes by S. bovis/gallolyticus releases various other inflammatory mediators (NO, free radicals, peroxynitriles, etc.) which could interfere directly or indirectly with the cell proliferation process. The recent studies conducted by our team revealed that S. gallolyticus is remarkably associated with colorectal cancer and adenoma when compared to the more dominant intestinal bacteria, B. fragilis. This provided evidence for a possible important role of S. gallolyticus in the carcinogenesis of colorectal cancer from pre-malignant polyps. In addition, we found that NF-κB and IL-8 rather than other transformation factors, p21, p27 and p53 acted as highly important mediators for the S. gallolyticus-

associated progression of colorectal adenoma to carcinoma [39]. And NF-κB most probably exerts a promoting carcinogenic effect while IL-8 exerts an angiogenic/propagating effect on colorectal mucosal cells Reverse transcriptase [39]. In addition, a more recent study done by our team showed a direct and active role of S. bovis/gallolyticus in colonizing colorectal cancer tissues leading to the development of colorectal cancer through inflammation-based sequel via, but not limited to, IL-1, COX-2, and IL-8 [40]. Another aspect of inflammatory cytokines, the local action of cytokines or of chemical mediators is able to promote vasodilatation and the enhancement of capillary permeability, which in turn was found to support the bacterial entry at tumor sites, and increase bacterial adherence to various cells [38, 89].