Helicobacter pylori

Chronic gastritis is an inflammation of the gastric mucosa and has multiple etiologies. Here we discuss the pathological alterations induced by Helicobacter pylori (HP) leading to chronic gastritis and the epigenetic bases underlying these changes. We review the histology of the normal gastric mucosa and overview the role of HP in the multistep cascade of GC. We attempt to define the role of the Operative Link for Gastritis Assessment (OLGA) staging system in assessing the risk of GC. The epigenetic bases of chronic gastritis, mainly DNA methylation, are presented through examples such as (i) the methylation of the promoter region of E-cadherin in HP-induced chronic gastritis and its reversion after HP eradication and (ii) the association of methylation of the promoter region of Reprimo, a p53-mediated cell cycle arrest gene, with aggressive HP strains in high risk areas for GC. In addition, we discuss the finding of RPRM as a circulating cell-free DNA, offering the opportunity for noninvasive risk assessment of GC. Finally, the integration of OLGA and tissue biomarkers, by systems pathology approach, suggests that severe atrophy has a greater risk for GC development if, in addition, overexpressed p73. This trial is registered with ClinicalTrials.gov NCT01774266

MicroRNA-335-5p and Gastrointestinal Tumors

Noncoding genomics, i.e., microRNAs and long coding RNAs (lncRNA), is an emerging topic in gastrointestinal tumors. In particular, the coordinate deregulation of miRNA-335-5p across these tumors and its potential clinical applications is an example of this scenario. This chapter discusses the pathogenetic role of miRNA-335-5p in esophageal, gastric, colon, liver, gallbladder, and pancreatic tumors. This pathogenetic role is examined in the context of the competing endogenous network, the language through lncRNA that reduce the quantity of miRNA available to target mRNA. The translational application of miRNA-335-5p, through the aberrant methylation of the promoter region of MEST—its host gene—as a potential biomarker for noninvasive detection of gastric cancer, is also discussed

In Silico analysis of Gastric carcinoma Serial Analysis of Gene Expression libraries reveals different profiles associated with ethnicity

Worldwide gastric carcinoma has marked geographical variations and worse outcome in patients from the West compared to the East. Although these differences has been explained by better diagnostic criteria, improved staging methods and more radical surgery, emerging evidence supports the concept that gene expression differences associated to ethnicity might contribute to this disparate outcome. Here, we collected datasets from 4 normal and 11 gastric carcinoma Serial Gene Expression Analysis (SAGE) libraries from two different ethnicities. All normal SAGE libraries as well as 7 tumor libraries were from the West and 4 tumor libraries were from the East. These datasets we compare by Correspondence Analysis and Support Tree analysis and specific differences in tags expression were identified by Significance Analysis for Microarray. Tags to gene assignments were performed by CGAP-SAGE Genie or TAGmapper. The analysis of global transcriptome shows a clear separation between normal and tumor libraries with 90 tags differentially expressed. A clear separation was also found between the West and the East tumor libraries with 54 tags differentially expressed. Tags to gene assignments identified 15 genes, 5 of them with significant higher expression in the West libraries in comparison to the East libraries. qRT-PCR in cell lines from west and east origin confirmed these differences. Interestingly, two of these genes have been associated to aggressiveness (COL1A1 and KLK10). In conclusion we found that in silico analysis of SAGE libraries from two different ethnicities reveal differences in gene expression profile. These expression differences might contribute to explain the disparate outcome between the West and the East

Epstein-Barr Virus–Associated Gastric Carcinoma: The Americas’ Perspective

Epstein-Barr virus (EBV) infection has been associated with different malignancies, and compelling evidence has shown that it may have a causative or at least contributing role in gastric carcinogenesis. EBV-associated gastric cancers have a unique molecular signature, which has defined this group of tumors as a distinctive molecular subtype of gastric cancer. This subtype has shown a greater incidence in the Americas than in the Asian countries. This chapter discusses about possible factors underlying these differences and the emerging roles of epigenetics in the pathogenesis of Epstein-Barr virus–associated gastric cancer

Improved survival of gastric cancer with tumour Epstein–Barr virus positivity: an international pooled analysis

About 9% of gastric carcinomas have Epstein–Barr virus (EBV) in the tumour cells, but it is unclear whether viral presence influences clinical progression. We therefore examined a large multicentre case series for the association of tumour EBV status with survival after gastric cancer diagnosis, accounting for surgical stage and other prognostic factors

The Helicobacter pylori Genome Project : insights into H. pylori population structure from analysis of a worldwide collection of complete genomes

Helicobacter pylori, a dominant member of the gastric microbiota, shares co-evolutionary history with humans. This has led to the development of genetically distinct H. pylori subpopulations associated with the geographic origin of the host and with differential gastric disease risk. Here, we provide insights into H. pylori population structure as a part of the Helicobacter pylori Genome Project (HpGP), a multi-disciplinary initiative aimed at elucidating H. pylori pathogenesis and identifying new therapeutic targets. We collected 1011 well-characterized clinical strains from 50 countries and generated high-quality genome sequences. We analysed core genome diversity and population structure of the HpGP dataset and 255 worldwide reference genomes to outline the ancestral contribution to Eurasian, African, and American populations. We found evidence of substantial contribution of population hpNorthAsia and subpopulation hspUral in Northern European H. pylori. The genomes of H. pylori isolated from northern and southern Indigenous Americans differed in that bacteria isolated in northern Indigenous communities were more similar to North Asian H. pylori while the southern had higher relatedness to hpEastAsia. Notably, we also found a highly clonal yet geographically dispersed North American subpopulation, which is negative for the cag pathogenicity island, and present in 7% of sequenced US genomes. We expect the HpGP dataset and the corresponding strains to become a major asset for H. pylori genomics

Escaping Antiangiogenic Therapy: Strategies Employed by Cancer Cells

Tumor angiogenesis is widely recognized as one of the “hallmarks of cancer”. Consequently, during the last decades the development and testing of commercial angiogenic inhibitors has been a central focus for both basic and clinical cancer research. While antiangiogenic drugs are now incorporated into standard clinical practice, as with all cancer therapies, tumors can eventually become resistant by employing a variety of strategies to receive nutrients and oxygen in the event of therapeutic assault. Herein, we concentrate and review in detail three of the principal mechanisms of antiangiogenic therapy escape: (1) upregulation of compensatory/alternative pathways for angiogenesis; (2) vasculogenic mimicry; and (3) vessel co-option. We suggest that an understanding of how a cancer cell adapts to antiangiogenic therapy may also parallel the mechanisms employed in the bourgeoning tumor and isolated metastatic cells delivering responsible for residual disease. Finally, we speculate on strategies to adapt antiangiogenic therapy for future clinical uses