Empirical evidence of the continuing improvement in cost efficiency of an endoscopic surveillance programme for gastric cancer in Singapore from 2004 to 2010

10.1186/1472-6963-13-139BMC Health Services Research131

Recurrent Fusion Genes in Gastric Cancer: CLDN18-ARHGAP26 Induces Loss of Epithelial Integrity.

Genome rearrangements, a hallmark of cancer, can result in gene fusions with oncogenic properties. Using DNA paired-end-tag (DNA-PET) whole-genome sequencing, we analyzed 15 gastric cancers (GCs) from Southeast Asians. Rearrangements were enriched in open chromatin and shaped by chromatin structure. We identified seven rearrangement hot spots and 136 gene fusions. In three out of 100 GC cases, we found recurrent fusions between CLDN18, a tight junction gene, and ARHGAP26, a gene encoding a RHOA inhibitor. Epithelial cell lines expressing CLDN18-ARHGAP26 displayed a dramatic loss of epithelial phenotype and long protrusions indicative of epithelial-mesenchymal transition (EMT). Fusion-positive cell lines showed impaired barrier properties, reduced cell-cell and cell-extracellular matrix adhesion, retarded wound healing, and inhibition of RHOA. Gain of invasion was seen in cancer cell lines expressing the fusion. Thus, CLDN18-ARHGAP26 mediates epithelial disintegration, possibly leading to stomach H(+) leakage, and the fusion might contribute to invasiveness once a cell is transformed. Cell Rep 2015 Jul 14; 12(2):272-285

Genetic factors associated with intestinal metaplasia in a high risk Singapore-Chinese population: a cohort study

BMC Gastroenterology97

Oncogenic Pathway Combinations Predict Clinical Prognosis in Gastric Cancer

Many solid cancers are known to exhibit a high degree of heterogeneity in their deregulation of different oncogenic pathways. We sought to identify major oncogenic pathways in gastric cancer (GC) with significant relationships to patient survival. Using gene expression signatures, we devised an in silico strategy to map patterns of oncogenic pathway activation in 301 primary gastric cancers, the second highest cause of global cancer mortality. We identified three oncogenic pathways (proliferation/stem cell, NF-κB, and Wnt/β-catenin) deregulated in the majority (>70%) of gastric cancers. We functionally validated these pathway predictions in a panel of gastric cancer cell lines. Patient stratification by oncogenic pathway combinations showed reproducible and significant survival differences in multiple cohorts, suggesting that pathway interactions may play an important role in influencing disease behavior. Individual GCs can be successfully taxonomized by oncogenic pathway activity into biologically and clinically relevant subgroups. Predicting pathway activity by expression signatures thus permits the study of multiple cancer-related pathways interacting simultaneously in primary cancers, at a scale not currently achievable by other platforms

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

Persepsyon sa sarili ng mga piling matandang dalaga at binata sa gitnang gulang

Ang deskriptibong pag-aaral na ito ay nagsasalarawan ng persepsyon sa sarili ng mga matandang dalaga at binata na nasa edad 40-60 sa aspetong pisikal, sosyal, emosyonal at sikolohikal. Ang mga kasagutan ng mga kalahok ay pinaghambing batay sa kasarian at antas ng pamumuhay. Gumamit ng malalimang pakikipanayam at sinuri ang mga datos sa pamamagitan ng content analysis. Base sa mga resulta, ang mga matandang dalaga at binata ay nakikita ang sarili na nakakadanas ng mga pisikal na pagbabago, hindi na palalabas, natatakot na walang mag-aalaga sa pagtanda at mas naging maingat sa kalusugan. Nakita ng mga matandang dalaga ang sarili na relihiyosa samantalang palakaibigan ang mga matandang binata. Para sa mga matandang binata, sila ay maaari pang mag-asawa, ang mga matandang dalaga ay hindi na. Samantala, ang mga nasa gitnang antas ay nakikita ang sarili na konsern sa pagpapaunlad ng sarili, ang mga nasa mababang antas naman ay ang pagreretiro. Ang mga nasa gitnang antas din ay masaya sa trabaho, samantalang ang mga nasa mababang antas ay hindi kuntento rito

ETIOLOGICAL STRUCTURE AND DIFFERENTIAL DIAGNOSTICS OF SALMONELLOSIS OF BIRDS

The article presents the results of a study of the etiological structure and differential diag-nostic signs of avian salmonellosis. When identifying bacteria isolated from 128 blood samples of chickens with the use of rapid test "Salmonella latex kit" established the dominance of cultures of the microorganisms Salmonella spp. - of 10.94% (14 samples); 10 strains (71,43%) were attributed to Salmonella gallinarum, 4 (of 28.57%) to Salmonella pullorum. The overall level of resistance of Salmonella to ampicillin - 57,58%; tetracycline - 60,61%; streptomycin - 66,67%; had to 57,58%; 60,61% and 66,67% are sensitivity to norfloxacin amounted to 69,70%, to ceftazidime - 78,79%, enrofloxacin - 57,58%, ciprofloxacin - 69,70% of the tested strains. At postmortem examination the most frequently detected signs of pericarditis, hemorrhagic pneumonia, aeroscout, catarrhal-hemorrhagic enteritis, perihepatitis, hyperplasia of the spleen. The most frequently detected signs of pericarditis, aeroscout, catarrhal-hemorrhagic gastroenterocolitis, perihepatitis, inflam-mation of the ovaries, hyperplasia of the spleen. Revealed signs of congestive hyperemia, macrophage reaction, hyperplasia and plasmocytomas of lymphocyte transformation, increase the permeability of microcirculatory vessels, lymphoid-cellular infil-tration of loose fibrous connective tissue, perivascular oedema, disseminated thrombosis, proliferation of lymphocytes from lymph nodes, spleen, liver, and pancreas. In violation of the porosity of the blood vessels of serous membranes of organs were observed extensive serous oedema, the output of the formed elements of blood and the loss of fibrinogen

Whole-genome reconstruction and mutational signatures in gastric cancer.

BACKGROUND: Gastric cancer is the second highest cause of global cancer mortality. To explore the complete repertoire of somatic alterations in gastric cancer, we combined massively parallel short read and DNA paired-end tag sequencing to present the first whole-genome analysis of two gastric adenocarcinomas, one with chromosomal instability and the other with microsatellite instability. RESULTS: Integrative analysis and de novo assemblies revealed the architecture of a wild-type KRAS amplification, a common driver event in gastric cancer. We discovered three distinct mutational signatures in gastric cancer--against a genome-wide backdrop of oxidative and microsatellite instability-related mutational signatures, we identified the first exome-specific mutational signature. Further characterization of the impact of these signatures by combining sequencing data from 40 complete gastric cancer exomes and targeted screening of an additional 94 independent gastric tumors uncovered ACVR2A, RPL22 and LMAN1 as recurrently mutated genes in microsatellite instability-positive gastric cancer and PAPPA as a recurrently mutated gene in TP53 wild-type gastric cancer. CONCLUSIONS: These results highlight how whole-genome cancer sequencing can uncover information relevant to tissue-specific carcinogenesis that would otherwise be missed from exome-sequencing data