Rhesus monkeys challenged with H. pylori and ENNG
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ABSTRACT:
ORGANISM(S): Macaca mulatta
PROVIDER: GSE38586 | GEO | 2013/06/07
SECONDARY ACCESSION(S): PRJNA168163
REPOSITORIES: GEO
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Project description:Gene expression was studied in samples from the stomach of Rhesus monkeys that have been infected with Helicobacter pylori and treated with a known carcinogen (Ethyl-nitro-nitrosoguanidine (ENNG)) that is similar to known nitrosamine dietary carcinogens. The samples represent the following: Biopsy 4689 is from animal 81G taken 55 months after inoculation with H. pylori and the start of the carcinogen ENNG Biopsy 4691 is from animal 63G taken 55 months after inoculation with H. pylori and the start of the carcinogen ENNG Biopsy 4709 is from animal 92F taken after 55 months of observation and no treatment (control). Gastric biopsies were obtained at the indicated times and RNA was harvested from the sample. All hybridizations were conducted against a common reference that was prepared using commercially obtained RNA isolated from the stomach of uninfected monkeys. Infection: Inoculated with H. pylori and treated with carcinogen ENNG (Treated) or control
2013-06-07 | E-GEOD-38586 | biostudies-arrayexpress
Project description:BACKGROUND & AIMS: Gastric cancer results from a combination of Helicobacter pylori (H pylori) infection, exposure to dietary carcinogens, and predisposing genetic make-up. Because the role of these factors in gastric carcinogenesis cannot be determined readily in human beings, the present study examined the role of an oral carcinogen and H pylori infection in rhesus monkeys. METHODS: Gastroscopies were performed in 23 monkeys assigned to 4 groups: controls; nitrosating carcinogen ethyl-nitro-nitrosoguanidine administration alone; and inoculation of a virulent H pylori strain alone (H), or in combination with ethyl-nitro-nitrosoguanidine (EH). Follow-up gastroscopies and biopsies were performed at 3-month intervals for 5 years for pathologic and molecular studies. RESULTS: Postinoculation, H and EH groups showed persistent infection and antral gastritis. Starting at 2 and 5 years, respectively, gastric intestinal metaplasia and intraepithelial neoplasia developed in 3 EH monkeys but in no other groups. Transcriptional analysis of biopsies at 5 years revealed group-specific expression profiles, with striking changes in EH monkeys, plus a neoplasia-specific expression profile characterized by changes in multiple cancer-associated genes. Importantly, this neoplastic profile was evident in nonneoplastic mucosa, suggesting that the identified genes may represent markers preceding cancer. CONCLUSIONS: Gastric intraglandular neoplasia is induced in primates when H pylori infection is associated with consumption of a carcinogen similar to the nitrosaminesfound in pickled vegetables, suggesting that H pylori and the carcinogen synergistically induce gastric neoplasia in primates. Monkey arrays used for analysis of the affect of Helicobacter pylori and diet on development of gastric cancer. Each RNA was hybridized against a common reference. Biopsy numbers represent the following in terms of descriptions used in publication of the paper... Each set of numbers/descriptions is organized in the following order: Biopsy#; Monkey#; Group Code on Fig 5 Biopsy #4674; AB24; E; E1 Biopsy #4684; 16G; E; E2 Biopsy #4716; 89G; H; H1 Biopsy #4724; 54H; H; H2 Biopsy #4720; 20G; H; H3 Biopsy #4710; 92F; C; C1 Biopsy #4714; 26G; C; C2 Biopsy #4712; 92G; C; C3 Biopsy #4726; 08G; H; H4 Biopsy #4722; 57G; H; H5 Biopsy #4718; 85G; H; H6 Biopsy #4694; 48H; HE NON; HE1 Biopsy #4686; 59H; HE NON; HE2 Biopsy #4690; 81G; HE NEO; HE3 Biopsy #4696; 36G; HE NEO; HE4 Biopsy #4692; 63G; HE NEO; HE5 Biopsy #4680; 76G; E; E3 Biopsy #4682; 52G; E; E4 Biopsy #4678; 15G; E; E5 Biopsy #4676; 93G; E; E6 Biopsy #4688; 47H; HE NON; HE6 A pathogenicity experiment design type is where an infective agent such as a bacterium, virus, protozoan, fungus etc. infects a host organism(s) and the infective agent is assayed. Infection: Rhesus monkeys were infected with H. pylori (+/-) Compound Based Treatment: Rhesus monkeys were treated with ENNG (N-ethyl-N-nitrosoguanidine) (+/-) pathogenicity_design
2009-10-07 | E-GEOD-18434 | biostudies-arrayexpress
Project description:BACKGROUND & AIMS: Gastric cancer results from a combination of Helicobacter pylori (H pylori) infection, exposure to dietary carcinogens, and predisposing genetic make-up. Because the role of these factors in gastric carcinogenesis cannot be determined readily in human beings, the present study examined the role of an oral carcinogen and H pylori infection in rhesus monkeys. METHODS: Gastroscopies were performed in 23 monkeys assigned to 4 groups: controls; nitrosating carcinogen ethyl-nitro-nitrosoguanidine administration alone; and inoculation of a virulent H pylori strain alone (H), or in combination with ethyl-nitro-nitrosoguanidine (EH). Follow-up gastroscopies and biopsies were performed at 3-month intervals for 5 years for pathologic and molecular studies. RESULTS: Postinoculation, H and EH groups showed persistent infection and antral gastritis. Starting at 2 and 5 years, respectively, gastric intestinal metaplasia and intraepithelial neoplasia developed in 3 EH monkeys but in no other groups. Transcriptional analysis of biopsies at 5 years revealed group-specific expression profiles, with striking changes in EH monkeys, plus a neoplasia-specific expression profile characterized by changes in multiple cancer-associated genes. Importantly, this neoplastic profile was evident in nonneoplastic mucosa, suggesting that the identified genes may represent markers preceding cancer. CONCLUSIONS: Gastric intraglandular neoplasia is induced in primates when H pylori infection is associated with consumption of a carcinogen similar to the nitrosaminesfound in pickled vegetables, suggesting that H pylori and the carcinogen synergistically induce gastric neoplasia in primates. Monkey arrays used for analysis of the affect of Helicobacter pylori and diet on development of gastric cancer. Each RNA was hybridized against a common reference. Biopsy numbers represent the following in terms of descriptions used in publication of the paper... Each set of numbers/descriptions is organized in the following order: Biopsy#; Monkey#; Group Code on Fig 5 Biopsy #4674; AB24; E; E1 Biopsy #4684; 16G; E; E2 Biopsy #4716; 89G; H; H1 Biopsy #4724; 54H; H; H2 Biopsy #4720; 20G; H; H3 Biopsy #4710; 92F; C; C1 Biopsy #4714; 26G; C; C2 Biopsy #4712; 92G; C; C3 Biopsy #4726; 08G; H; H4 Biopsy #4722; 57G; H; H5 Biopsy #4718; 85G; H; H6 Biopsy #4694; 48H; HE NON; HE1 Biopsy #4686; 59H; HE NON; HE2 Biopsy #4690; 81G; HE NEO; HE3 Biopsy #4696; 36G; HE NEO; HE4 Biopsy #4692; 63G; HE NEO; HE5 Biopsy #4680; 76G; E; E3 Biopsy #4682; 52G; E; E4 Biopsy #4678; 15G; E; E5 Biopsy #4676; 93G; E; E6 Biopsy #4688; 47H; HE NON; HE6 A pathogenicity experiment design type is where an infective agent such as a bacterium, virus, protozoan, fungus etc. infects a host organism(s) and the infective agent is assayed. Infection: Rhesus monkeys were infected with H. pylori (+/-) Compound Based Treatment: Rhesus monkeys were treated with ENNG (N-ethyl-N-nitrosoguanidine) (+/-)
2009-10-07 | GSE18434 | GEO
Project description:We used the rhesus macaque model to study the effects of the cag pathogenicity island (cag PAI) on the H. pylori host-pathogen interaction. Specific pathogen free (SPF) monkeys with no prior exposure to H. pylori were experimentally challenged with wild type (WT) H. pylori strain J166 (N=4) or its cag PAI isogenic knockout (KO, N=4). Animals underwent endoscopy before and 1, 4, 8, and 13 wks after challenge. Gastric biopsies were collected for quantitative culture, histopathology, and host gene expression. Quantitative cultures showed that all experimentally challenged animals were infected with WT H. pylori or its isogenic cag PAI KO. Histopathology demonstrated that inflammation and expansion of the lamina propria were attenuated in animals infected with KO compared to WT. Microarray analysis was performed on challenged animals before and 1 and 13 wks after challenge, and on unchallenged control animals (N=4). Of the 119 up-regulated genes in the WT-infected animals, several encode innate antimicrobial; effector proteins, including elafin, siderocalin, DMBT, DUOX2, and several novel paralogues of human defensin-2. Quantitative RT-PCR analysis showed that high level induction of each of these genes was dependent upon the presence of the cag PAI. Immunohistochemistry confirmed increased defensin epithelial cell staining in animals challenged with WT H. pylori compared to either KO-challenged or uninfected control animals. We propose that one function of the cag PAI is to induce an antimicrobial host response that serves to increase the competitive advantage of H. pylori in the gastric niche. Experiment Overall Design: Twelve male and female rhesus macaques (Macaca mulatta) housed at the California National Primate Research Center (CNPRC) were hand raised by nursery staff to obtain Specific Pathogen (Helicobacter pylori) Free (SPF) experimental animals. At six months of age the animals were documented to be uninfected with H. pylori by serology, histology, and cultures of gastric biopsies using methods reported previously (Solnick et al., 1999). Two experimental groups of four SPF animals were challenged with either wild type (WT) H. pylori J166 or an isogenic PAI knockout (KO). A third group of four SPF animals served as uninoculated controls. Monkeys were housed indoors in separate cages throughout the duration of the experiment. All experiments were approved by the Research Advisory Committee of the CNPRC and the Institutional Animal Care and Use Committee at the University of California.Antrum and corpus stomach biopsies from rhesus macaques infected with wild type Helicobacter pylori J166, isogenic cag-PAI knockout strain, or mock infected were pooled. Biopsies were taken prior to bacterial inoculation and at 1 and 13 weeks post infection. Control biopsies were taken according to the same time line. Four animals were used for each experimental condition.
2008-06-16 | E-GEOD-8749 | biostudies-arrayexpress
Project description:We have employed whole microRNA microarray with the potential to distinguish H.pylori infection.Among the 470 human miRNAs represented on the array chip, 228 were undetectable or expressed below the background and so were eliminated, leaving 242 miRNAs for the supervised analysis. When comparing 10 H. pylori-negative and nine H. pylori-positive subjects, 55 miRNAs were deemed significantly different on the basis of microRNA arrays. During endoscopy, a biopsy specimen was obtained from the gastric antrum along the lesser curvature. Biopsies of 10 H. pylori-negative and nine H. pylori-positive patients' subjects were performed.Exclusion criteria were: age <18 or >80 y, pregnancy, body mass index (BMI) >30 kg/m2, diabetes mellitus, cachectic state (including cancer), systemic infection, liver disease, renal impairment, use of medications effective against H. pylori during the preceding 3 months, alcohol abuse, drug addiction, and chronic corticosteroid or nonsteroidal anti-inflammatory drug use. None of the subjects had undergone gastrointestinal surgery.
2010-05-16 | E-GEOD-19769 | biostudies-arrayexpress
Project description:Helicobacter pylori (H. pylori) infection and excessive salt intake are known as important risk factors for stomach cancer in humans. However, interactions of these two factors with gene expression profiles during gastric carcinogenesis remain unclear. In this study, we established a mouse gastric tumor model combining a chemical carcinogen, H. pylori infection and a high-salt diet. The tumor incidence and multiplicity in N-methyl-N-nitrosourea-treated mice were significantly increased by combination of H. pylori with a high-salt diet. In addition, detailed examination indicated that excessive salt could regulate progression of gastric tumor. Global gene expression profiles in glandular stomach of the mouse model were investigated by cDNA microarray analysis, and 36 and 31 more than twofold up-regulated and down-regulated genes, respectively, were detected in the H. pylori-infection and high-salt diet combined group compared with the other groups. Quantitative RT-PCR confirmed significant over-expression of several candidate genes including Cd177, Reg3g, and Muc13. These results suggest that our mouse model combined with H. pylori infection and high-salt diet is useful for gene expression profiling in gastric carcinogenesis.
2011-05-25 | GSE29444 | GEO
Project description:Helicobacter pylori (H. pylori) infection and excessive salt intake are known as important risk factors for stomach cancer in humans. However, interactions of these two factors with gene expression profiles during gastric carcinogenesis remain unclear. In this study, we established a mouse gastric tumor model combining a chemical carcinogen, H. pylori infection and a high-salt diet. The tumor incidence and multiplicity in N-methyl-N-nitrosourea-treated mice were significantly increased by combination of H. pylori with a high-salt diet. In addition, detailed examination indicated that excessive salt could regulate progression of gastric tumor. Global gene expression profiles in glandular stomach of the mouse model were investigated by cDNA microarray analysis, and 36 and 31 more than twofold up-regulated and down-regulated genes, respectively, were detected in the H. pylori-infection and high-salt diet combined group compared with the other groups. Quantitative RT-PCR confirmed significant over-expression of several candidate genes including Cd177, Reg3g, and Muc13. These results suggest that our mouse model combined with H. pylori infection and high-salt diet is useful for gene expression profiling in gastric carcinogenesis. Five- to six-week-old male C57BL/6J mice (CLEA Japan, Tokyo, Japan) were inoculated with Helicobacter pylori (Sydney strain 1) (Sample No. 2 and 4) or Brucella broth (Sample No. 1 and 3). The animals were administered 120 ppm N-methyl-N-nitrosourea (MNU) in their drinking water on alternate weeks (total exposure, 5 weeks). Mice were given basal diet (CE-2, CLEA Japan) (Sample No. 1 and 2) or high-salt diet containing 10% NaCl (Sample No. 3 and 4). At 40 weeks, the animals were subjected to deep anesthesia and laparotomy with excision of the stomach.
2011-05-25 | E-GEOD-29444 | biostudies-arrayexpress
Project description:High temperature requirement A (HtrA) is a serine protease secreted by the group-I carcinogen Helicobacter pylori (H. pylori). The human cell adhesion protein and tumor suppressor E-cadherin (hCdh1) expressed on the surface of gastric epithelial cells was identified as the first HtrA substrate. HtrA-mediated hCdh1 cleavage and subsequent disruption of intercellular adhesion are considered as important steps in H. pylori pathogenesis. In this study, we performed a proteomic profiling of H. pylori HtrA (HpHtrA) to decipher the complex mechanism how H. pylori can interfere with epithelial barrier integrity.
2022-02-17 | PXD025360 | Pride
Project description:The aim of this study is to identify alterations induced in gastric mucosa of mice exposed to Pteridium aquilinum and/or infected with Helicobacter pylori, in order to identify genes that are induced by bracken fern exerts exacerbating effects on gastric lesions associated to the infection. Six groups of C57Bl/6 mice were be used: 1) control, 2) infected Helicobacter pylori, 3) treated with Bracken fern extract orogastrically, 4) treated with Bracken fern extract in drinking water, 5) infected Helicobacter pylori + treated with Bracken fern extract orogastrically, 6) infected Helicobacter pylori + treated with Bracken fern extract in drinking water. The infection procedure was performed using an orogastric inoculation of H.pylori (strain SS1) twice in the first week. The RNA isolation was done in triplicate (3 mice per each condition). Further evaluation of morphological alterations on gastric mucosa, proliferative index and induction of DNA strand breaks will be performed in the mice stomach exposed to Pteridium aquilinum infected or not with Helicobacter pylori. Alterations of glycosylation in gastric tissues will also evaluated.
2011-09-07 | E-GEOD-31991 | biostudies-arrayexpress
Project description:Helicobacter pylori strains USU101 was infected into macaques, some of which were treated with the dietary carcinogen ENNG. After 5 years, H. pylori isolates were obtained by endoscopy followed by culture. The resulting strains were analyzed for differences in gene content by array CGH.
2014-08-18 | GSE60405 | GEO