Changes in gene expression during the transition from inflammation to cancer following Helicobacter felis infection
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ABSTRACT:
ORGANISM(S): Mus musculus Homo sapiens
PROVIDER: GSE27361 | GEO | 2011/02/17
SECONDARY ACCESSION(S): PRJNA137027
REPOSITORIES: GEO
Similar Datasets
Project description:We are now trying to elucidate the mechanism of Helicobacter-induced gastritis and gastric cancer. To identify genes involved in these Helicobacter-associated diseases, we infected Helicobacter felis to INS-GAS (insulin-gastrin transgenic) mice (C57BL/6 background) which shows accelerated development of gastritis and gastric cancer. Three infected mice and three uninfected control mice (6 in total) were sacrificed periodically (2, 4, 6, 8 months after the infection), and total RNA was isolated from each stomach. These samples are subjected to gene microarray analysis. Samples were obtained from mouse stomachs at 2, 4, 6, and 8/9 month post infection intervals. Control time points were taken at 0, 2, 4, 6, and 8 months. All samples, 22 in total, were hybridized to the GLYCOv2 array.
2011-02-17 | E-GEOD-27361 | biostudies-arrayexpress
Project description:We have previously reported human gastrin overexpressing transgenic mice (=INS-GAS mice) and Helicobacter felis (=H.felis) infection synergistically accelerated gastric cancer in mice stomachs. (Wang et al 2000) Using this mouse model, we employed microarray analysis of gene expression profiling to identify gastric cancer-specific genes. Keywords: disease state analysis
2006-04-13 | GSE4651 | GEO
Project description:We have previously reported human gastrin overexpressing transgenic mice (=INS-GAS mice) and Helicobacter felis (=H.felis) infection synergistically accelerated gastric cancer in mice stomachs. (Wang et al 2000) Using this mouse model, we employed microarray analysis of gene expression profiling to identify gastric cancer-specific genes. Experiment Overall Design: 30 male INS-GAS mice (FVB/N background) were divided into groups: 15 mice were infected with H.felis at the age of 2-3 months and another 15 mice were not infected. 30 male non-transgenic FVB/N mice were also divided into 2 groups: 15 mice were infected with H.felis at the age of 2-3 months and another 15 mice were not infected. All mice were sacrificed after 6 months of H.felis infection, and total RNAs were extracted from whole stomachs. Experiment Overall Design: Histological analysis confirmed all of the stomachs in H.felis infected INS-GAS mice (=INSGAS+Hf) had intra-epithelial gastric cancer, and some of them also had invasion into submucosa, but none of them had distant metastatic lesions. Other 3 control groups had following histology in stomachs. (1) non-transgenic mice with H.felis infection (=FVB+Hf): severe intestinal metaplasia and/or mild dysplasia. (2) INS-GAS mice without infection (=INSGAS wt): severe atrophic gastritis and/or mild intestinal metaplasia (3) non-transgenic mice without infection (=FVB wt): normal stomach. Total RNAs extracted from each mouse in 4 different groups were used for microarray analysis of Affymetrix GeneChip. Experiment Overall Design: Up- or down-regulated genes in INSGAS+Hf group compared with all 3 control groups (FVB+HF, INSGAS wt and FVB wt) may represent gastric cancer-specific genes.
2008-06-13 | E-GEOD-4651 | biostudies-arrayexpress
Project description:Background & Aims: Previous studies have suggested that dietary folic acid (FA) can protect against certain types of cancers. However, the findings have varied and the mechanisms by which this vitamin exerts chemopreventive effects remain to be clarified. We examined the effects of FA supplementation on DNA methylation, gene expression and gastric dysplasia in a transgenic mouse model that is etiologically and histologically well matched with human gastric cancers. Methods: Hypergastrinemic mice (INS-GAS) infected with Helicobacter felis were studied at multiple stages of gastric dysplasia and early cancer, with FA supplementation initiated both at weaning and later in life. Global DNA methylation was assessed by a methylation-sensitive cytosine incorporation assay, bisulfite pyrosequencing of B1 repetitive elements and immunohistochemistry (IHC) with anti-5-methylcytosine. We also profiled gene expression in the same tissues. Results: We found a decrease in global DNA methylation and tissue folate and an increase in serum homocysteine with progression of gastric dysplasia. FA supplementation prevented this loss of global DNA methylation and markedly reduced gastric dysplasia and mucosal inflammation. FA protected against the loss of global DNA methylation both in the dysplastic gastric epithelial cells and in gastric stromal myofibroblasts. In addition, FA supplementation had an anti-inflammatory effect, as indicated by expression profiling and IHC for lymphocyte markers. Conclusions: We conclude that FA supplementation is chemopreventive in this model of Helicobacter-associated gastric cancer. The beneficial effect of FA is likely due to its ability to reverse global loss of methylation and suppress inflammation. Study the difference in gene expression between transgenic hypergastrinemic (INS-GAS) mice fed a folate-supplemented diet and a diet with normal folate content. Because folate had a substantial protective effect, we matched the animals not only by folate status but also by dysplasia score (DYS). The degree of dysplasia was scored on a 1-4 scale. True replicates are not included. The first five samples are from folate supplemented animals, and the latter five are from controls on regular chow.
2011-07-20 | E-GEOD-30830 | biostudies-arrayexpress
Project description:Background & Aims: Previous studies have suggested that dietary folic acid (FA) can protect against certain types of cancers. However, the findings have varied and the mechanisms by which this vitamin exerts chemopreventive effects remain to be clarified. We examined the effects of FA supplementation on DNA methylation, gene expression and gastric dysplasia in a transgenic mouse model that is etiologically and histologically well matched with human gastric cancers. Methods: Hypergastrinemic mice (INS-GAS) infected with Helicobacter felis were studied at multiple stages of gastric dysplasia and early cancer, with FA supplementation initiated both at weaning and later in life. Global DNA methylation was assessed by a methylation-sensitive cytosine incorporation assay, bisulfite pyrosequencing of B1 repetitive elements and immunohistochemistry (IHC) with anti-5-methylcytosine. We also profiled gene expression in the same tissues. Results: We found a decrease in global DNA methylation and tissue folate and an increase in serum homocysteine with progression of gastric dysplasia. FA supplementation prevented this loss of global DNA methylation and markedly reduced gastric dysplasia and mucosal inflammation. FA protected against the loss of global DNA methylation both in the dysplastic gastric epithelial cells and in gastric stromal myofibroblasts. In addition, FA supplementation had an anti-inflammatory effect, as indicated by expression profiling and IHC for lymphocyte markers. Conclusions: We conclude that FA supplementation is chemopreventive in this model of Helicobacter-associated gastric cancer. The beneficial effect of FA is likely due to its ability to reverse global loss of methylation and suppress inflammation.
2011-07-21 | GSE30830 | GEO
Project description:Background: Helicobacter pylori (H. pylori) infection is a known cause of many digestive diseases, including gastritis, peptic ulcers, and gastric cancer. However, the underlying mechanism(s)by which H. pylori infection triggers these disorders are still not clearly understood. Methods: We have developed an accelerated disease progression mouse model, which leverages mice deficient in the myeloid differentiation primary response 88 gene (Myd88-/-) infected with Helicobacter felis (H. felis) Findings: In this study, we found that H. felis-induced inflammation in Myd88-/- mice progressed to high-grade dysplasia, driven by activation of the type I interferon (IFN-I) signaling pathway and upregulation of its downstream targets, IFN-stimulated genes (ISGs). We also observed enrichment of IFN stimulated-response element (ISRE) motifs in the promoters of upregulated genes, further supporting the involvement of this pathway. In contrast, mice deficient in Toll/interleukin-1 receptor (TIR)-domain-containing adaptor inducing interferon-β (TRIF, TrifLps2) did not progress to severe gastric pathology after H. felis infection, implicating the TRIF signaling pathway in disease pathogenesis and progression. Additionally, analysis of gastric biopsy samples from human gastric cancer patients illustrated that low expression of Myd88 and high expression of Trif were both significantly correlated with poor survival. Interpretation: Our study using an accelerated animal model for gastric cancer and gastric biopsy samples from patients demonstrated that activation of the TRIF-IFN-I signaling pathway promotes Helicobacter-induced disease progression toward severe gastric pathology and gastric cancer development. This represents a potential target for therapeutic intervention, and further exploration may lead to the identification of novel treatment strategies.
2024-04-17 | GSE250438 | GEO
Project description:Gli1 is necessary for the progression from chronic gastric inflammation to metaplasia in the stomach. We therefore compared the expression patterns between 6-month H. felis infected WT and Gli1-/- stomachs. Pooled tissue from the gastric fundi of 3 mice per group. Groups are WT, WT + H. felis (6 months), Gli1-/-, and Gli1-/- +H. felis (6 months). All the infected and control mice were obtained from the same experiment.
2013-01-24 | E-GEOD-43693 | biostudies-arrayexpress
Project description:Helicobacter pylori (H. pylori) is a human pathogen that infects almost half of the world’s population. Infection with H. pylori is frequently associated with chronic gastritis and can even lead to gastric and duodenal ulcers and gastric cancer. Although the persistent colonization of H. pylori and the development of H. pylori-associated gastritis remain poorly understood, it is believed that, in gastric mucosa, the modulated gastric epithelial cells (GECs) by H. pylori are key contributors. We used microarrays to detail the global programme of gene expression in Helicobacter pylori infected-gastric epithelial cell line AGS cells and identified up-regulated genes induced by Helicobacter pylori infection.
2024-04-18 | GSE264263 | GEO
Project description:Gli1 is necessary for the progression from chronic gastric inflammation to metaplasia in the stomach. We therefore compared the expression patterns between 6-month H. felis infected WT and Gli1-/- stomachs.
2013-01-24 | GSE43693 | GEO
Project description:Helicobacter pylori infection reprograms host gene expression and influences various cellular processes, which have been investigated by cDNA microarray in vitro culture cells and in vivo patients of the chronic abdominal complaint. In this study，the effects of H. pylori infection on host gene expression in the gastric antral mucosa of patients with chronic gastritis were examined. The gastric antral mucosa was obtained from a total of 6 untreated patients undergoing gastroscopic and pathologic confirmation of chronic superficial gastritis. Three patients infected by H. pylori and 3 patients uninfected were used to cDNA microarray experiment.
2012-04-29 | E-GEOD-30042 | biostudies-arrayexpress