ORCID Profile
0000-0001-9112-6028
Current Organisation
Erasmus MC
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Publisher: MDPI AG
Date: 12-11-2021
DOI: 10.3390/BIOMEDICINES9111680
Abstract: Gastric cancer (GC) is one of the global leading causes of cancer death. The association between Helicobacter pylori, which is a predominant risk factor for GC, with GC development has been well-studied. Recently, accumulating evidence has demonstrated the presence of a large population of microorganisms other than H. pylori in the human stomach. Existing sequencing studies have revealed microbial compositional and functional alterations in patients with GC and highlighted a progressive shift in the gastric microbiota in gastric carcinogenesis with marked enrichments of oral or intestinal commensals. Moreover, using a combination of gastric bacterial signatures, GC patients could be significantly distinguished from patients with gastritis. These findings, therefore, emphasize the importance of a collective microbial community in gastric carcinogenesis. Here, we provide an overview of non-H. pylori gastric microbes in gastric carcinogenesis. The molecular mechanisms of gastric microbes-related carcinogenesis and potential clinical applications of gastric microbiota as biomarkers of GC are also explored.
Publisher: Springer Science and Business Media LLC
Date: 07-06-2021
DOI: 10.1038/S41467-021-23641-8
Abstract: Barrett’s esophagus in gastrointestinal reflux patients constitutes a columnar epithelium with distal characteristics, prone to progress to esophageal adenocarcinoma. HOX genes are known mediators of position-dependent morphology. Here we show HOX collinearity in the adult gut while Barrett’s esophagus shows high HOXA13 expression in stem cells and their progeny. HOXA13 overexpression appears sufficient to explain both the phenotype (through downregulation of the epidermal differentiation complex) and the oncogenic potential of Barrett’s esophagus. Intriguingly, employing a mouse model that contains a reporter coupled to the HOXA13 promotor we identify single HOXA13-positive cells distally from the physiological esophagus, which is mirrored in human physiology, but increased in Barrett’s esophagus. Additionally, we observe that HOXA13 expression confers a competitive advantage to cells. We thus propose that Barrett’s esophagus and associated esophageal adenocarcinoma is the consequence of expansion of this gastro-esophageal HOXA13 -expressing compartment following epithelial injury.
Publisher: Springer Science and Business Media LLC
Date: 18-03-2019
DOI: 10.1007/S00705-019-04215-Y
Abstract: Rotaviruses and noroviruses are the most important viral causes of acute gastroenteritis in children. While previous studies of acute gastroenteritis in Indonesia mainly focused on rotavirus, here, we investigated the burden and epidemiology of norovirus and rotavirus disease. Children less than five years of age hospitalized with acute gastroenteritis were enrolled in this study from January to December 2015 at three participating hospitals. Rotavirus was detected by enzyme immunoassay (EIA), followed by genotyping by reverse transcription PCR (RT-PCR). Norovirus genogroups were determined by TaqMan-based quantitative RT-PCR. Among 406 enrolled children, 75 (18.47%), 223 (54.93%) and 29 (7.14%) cases were positive for norovirus, rotavirus and both viruses (mixed infections), respectively. Most cases clinically presented with fever, diarrhea, vomiting and some degree of dehydration. The majority (n = 69/75 [92%]) of the noroviruses identified belonged to genogroup II, and several genotypes were identified by sequencing a subset of s les. Among 35 s les tested for rotavirus genotype, the most prevalent genotype was G3P[8] (n = 30/35 [85.6%]). Our study suggests that the burden of norovirus diseases in Indonesian children should not be underestimated. It also shows the emergence of rotavirus genotype G3P[8] in Indonesia.
Publisher: Elsevier BV
Date: 03-2017
DOI: 10.1038/MI.2016.65
Abstract: Thiopurines are commonly used drugs in the therapy of Crohn's disease, but unfortunately only show a 30% response rate. The biological basis for the thiopurine response is unclear, thus h ering patient selection prior to treatment. A genetic risk factor associated specifically with Crohn's disease is a variant in ATG16L1 that reduces autophagy. We have previously shown that autophagy is involved in dendritic cell (DC)-T-cell interactions and cytoskeletal regulation. Here we further investigated the role of autophagy in DC cytoskeletal modulation and cellular trafficking. Autophagy-deficient DC displayed loss of filopodia, altered podosome distribution, and increased membrane ruffling, all consistent with increased cellular adhesion. Consequently, autophagy-deficient DC showed reduced migration. The cytoskeletal aberrations were mediated through hyperactivation of Rac1, a known thiopurine target. Indeed thiopurines restored the migratory defects in autophagy-deficient DC. Clinically, the ATG16L1 risk variant associated with increased response to thiopurine treatment in patients with Crohn's disease but not ulcerative colitis. These results suggest that the association between ATG16L1 and Crohn's disease is mediated at least in part through Rac1 hyperactivation and subsequent defective DC migration. As this phenotype can be corrected using thiopurines, ATG16L1 genotyping may be useful in the identification of patients that will benefit most from thiopurine treatment.
Publisher: Elsevier BV
Date: 12-2017
DOI: 10.1016/J.BPG.2017.09.010
Abstract: Advances in research techniques have made it possible to map the microbial communities in the gastrointestinal (GI) tract, where the majority of bacteria in the human body reside. Disturbances in these communities are referred to as dysbiosis and have been associated with GI cancers. Although dysbiosis is observed in several GI malignancies, the specific role of these changes has not been understood to the extent of Helicobacter pylori (HP) in gastric cancer (GC). This review will address the bacterial communities along the GI tract, from the oral cavity to the anal canal, particularly focusing on bacterial dysbiosis and carcinogenesis. Just as non-HP bacteria in the stomach may interact with HP in gastric carcinogenesis, the same may hold true for other GI tract malignancies, where an interplay between microbes in carcinogenesis seems conceivable, especially in colorectal cancer (CRC). In the last part of this review we will discuss the potential mechanisms of bacterial dysbiosis in GI carcinogenesis.
Publisher: Informa UK Limited
Date: 29-12-2021
Publisher: Elsevier BV
Date: 2018
DOI: 10.1016/J.BBCAN.2017.11.003
Abstract: Helicobacter Pylori is a gram negative rod shaped microaerophilic bacterium that colonizes the stomach of approximately half the world's population. Infection with c may cause chronic gastritis which via a quite well described process known as Correas cascade can progress through sequential development of atrophic gastritis, intestinal metaplasia and dysplasia to gastric cancer. H. pylori is currently the only bacterium that is classified as a class 1 carcinogen by the WHO, although the exact mechanisms by which this bacterium contributes to gastric carcinogenesis are still poorly understood. Only a minority of H. pylori-infected patients will eventually develop gastric cancer, suggesting that host factors may be important in determining the outcome of H. pylori infection. This is supported by a growing body of evidence suggesting that the host genetic background contributes to risk of H. pylori infection and gastric carcinogenesis. In particular single nucleotide polymorphisms in genes that influence bacterial handling via pattern recognition receptors appear to be involved, further strengthening the link between host risk factors, H. pylori incidence and cancer. Many of these genes influence cellular pathways leading to inflammatory signaling, inflammasome formation and autophagy. In this review we summarize known carcinogenic effects of H. pylori, and discuss recent findings that implicate host genetic pattern recognition pathways in the development of gastric cancer and their relation with H. pylori.
Publisher: Elsevier BV
Date: 02-2015
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Maikel Peppelenbosch.