LAUSR

In their comprehensive review Mentis et al. [1] discussed some molecular biological mechanisms involved in Helicobacter pylori infection (Hp-I)-related gastric cancer (GC) biology such as the role of stem cells and the link between Hp-I and gastrointestinal microbiota (GI-M). Moreover, they posed some «unsolved conundrums» such as the following: Hp-I induces gastric and duodenal inflammation, but is only linked to GC. This claim, however, is incomplete, because Hp-I is also linked with duodenal adenomas/carcinomas [2]. Moreover, Hp-I induces lower GI tract inflammation, thereby promoting oncogenesis [3, 4]. In this regard, we wish to add some additional data involving Hp-I in upper and lower GI tract oncogenesis. Concerning the role of stem cells in Hp-I-related GC, we earlier reviewed [5] mechanisms of Hp and stem cell interaction in GC such as: activation of the Wnt/β-catenin signaling pathway; CagA impact on the fibroblast growth factor-signal pathways implicated in the development of GC; enhancing transforming growth factor-β/bone morphogenetic proteins signal pathway involved in GC cells invasion; sonic hedgehog signaling dysregulation; and recruitment of mesenchymal stem cells and/or bone marrow-derived stem cells (BMDSCs), also mentioned in one original study (2004) by the authors [1], in the course of chronic inflammatory condition, that gains stepwise transformation to GC cells [5]. Likewise, such aforementioned mechanisms have been confirmed by more recent data [6], further indicated that Hp-I activates epithelial–mesenchymal transition pathway and induces the development of GC stem cells (CSCs), such as CD44(+) [7]. Regarding the latter aspect, using CSC and/or BMDSCs marker CD44, the CD44(+) gastric CSCs appear to display the stem cell self-renewal properties. Moreover, Hp is responsible for CD44(+) increased expression, indicating a potential Hp induction of CD44(+) gastric CSCs implicated in gastric tumorigenesis [3]. Furthermore, our studies showed presence of cyclin D1 involved in GC cell proliferation, as well as CD34 expressed on hematopoietic stem cells and neovessels in human Hp-related GC specimens [8]. Beyond GC, our studies also showed CD44(+) augmented expression in human Hp-connected colorectal adenoma (CRA) and colorectal cancer (CRC) tissues [3]. Therefore, Hp-I could have an impact on colon oncogenesis by stimulating CSCs or recruiting BMDSCs, similar to upper GI Hp-I-connected chronic inflammationmetaplasia-dysplasia sequence and BMDSCs recruitment that contribute to oncogenesis [3]. Thus further large-scale relative studies are warranted. BMDSCs might also contribute to the pathogenesis of Barrett’s esophagus (BE) [9], a complication of gastroesophageal reflux disease (GERD), which predisposes to BErelated esophageal adenocarcinoma (EAC) development. In this concern, it has been proposed that chronic Hp-I induces atrophic gastritis accompanied by decreased acid secretion and acid reflux, thereby reducing the risk of GERD and its related BE and EAC. However, this conventional consideration might represent a double-edged sword one view. Cellular and Molecular Life Sciences