bovis/gallolyticus can penetrate into the bloodstream through epithelial, oropharyngeal, dermal, respiratory, gastrointestinal, or urogenital lesions [88]. On the other hand, the ulceration of neoplastic lesions are found to be unable to form a consistent pathway

for the gut microorganisms to enter the bloodstream [7]. The access of S. bovis/gallolyticus into blood circulation MK0683 in vitro does not explain the cases of patients with infectious endocarditis and non-ulcerated colonic polyps [81]. Above all, S. bovis/gallolyticus bacteria were found to be actively engaged in triggering severe inflammatory reaction in colorectal mucosa, inducing inflammatory and angiogenic cytokines leading to the formation of free radicals that are implicated in the development or propagation of all types of human cancers [27, 29, 37, 39, 40, 89]. Accordingly, too many clues were found supporting the etiological role of S. bovis/gallolyticus in the development of colorectal tumors; therefore, it is very difficult to assume a non-etiological role of these bacteria. Hence, a more detailed overview is needed to clarify the underlying mechanisms that could be pursued by S. bovis/gallolyticus for the etiology or propagation of colorectal find more tumors. The hypothesized mechanisms of the etiological association of S. bovis/gallolyticus with colorectal tumors The other big question in the current topic, what mechanisms S. bovis/gallolyticus

undertakes Selleck Decitabine to induce, promote, or/and progress the development of neoplastic lesions. The most possible mechanisms are as follows: Carcinogenesis via cytokine-dependent inflammation Chronic inflammation is associated with many malignant changes. Host genetic polymorphisms of the adaptive and innate immune response play an important role in bacteria-induced cancer formation [90–92]. Therefore, studying

the immunological responses to chronic bacterial infections yields important clues on the carcinogenic mechanisms of bacterial persistent infections and clarifies the relationship between inflammation and cancer [93, 94]. Clinical studies have shown that the use of non-steroidal anti-inflammatory drugs is associated with reduced risk of gastrointestinal cancers [95]; hence, these studies provide evidence on the role of inflammation in the development of gastrointestinal cancers. In vitro experiments showed that the binding of S. bovis wall extracted antigens to various cell lines, including human colonic cancer cells (Caco-2), stimulated the production of inflammatory cytokines by those cells [38, 96]. In other studies, the production of inflammatory cytokines in response to S. bovis/gallolyticus, such as TNF-α, IL-1β, IL-6, and IL-8, is found to contribute to the normal defense mechanisms of the host [89, 97] leading to the formation of HDAC inhibitor mechanism nitric oxide and free radicals such as superoxide, peroxynitrites, hydroxyl radicals, and alkylperoxy radicals [96, 98].