Hypertrophic gastropathy in Helicobacter felis-infected wild-type C57BL/6 mice and p53 hemizygous transgenic mice

Fox, James G.; Li, Xiantang; Cahill, Rachel; Andrutis, Karl A.; Rustgi, Anil K.; Odze, Robert D.; Wang, Yichen

doi:10.1053/gast.1996.v110.pm8536852

Cited by 167 publications

(136 citation statements)

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“…(70,71). Although C57BL/6 mice infected with H. felis recapitulated the loss of parietal cells and chief cells observed in human patients, mice lacking T and B cells infected with H. felis showed no changes in gastric epithelial cells (20,21,70,72). By contrast, infection of mice lacking B cells but able to mount a normal T cell response did lead to severe atrophy and metaplasia.…”

Section: Host Factors That Affect the Development Of Gastric Cancer Gmentioning

confidence: 84%

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Inflammation, atrophy, and gastric cancer

Fox

Wang²

2007

J. Clin. Invest.

694

626

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The association between chronic inflammation and cancer is now well established. This association has recently received renewed interest with the recognition that microbial pathogens can be responsible for the chronic inflammation observed in many cancers, particularly those originating in the gastrointestinal system. A prime example is Helicobacter pylori, which infects 50% of the world's population and is now known to be responsible for inducing chronic gastric inflammation that progresses to atrophy, metaplasia, dysplasia, and gastric cancer. This Review provides an overview of recent progress in elucidating the bacterial properties responsible for colonization of the stomach, persistence in the stomach, and triggering of inflammation, as well as the host factors that have a role in determining whether gastritis progresses to gastric cancer. We also discuss how the increased understanding of the relationship between inflammation and gastric cancer still leaves many questions unanswered regarding recommendations for prevention and treatment.

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Section: Host Factors That Affect the Development Of Gastric Cancer Gmentioning

confidence: 84%

“…SPEM is more strongly associated with gastric cancer than is intestinal metaplasia and might be the precursor to the cancerous lesion (18,19). In some mouse models of gastric cancer, SPEM consistently emerges in the chronically inflamed stomach and clearly precedes and gives rise to gastric cancer (20,21).…”

Section: Atrophic Gastritis and Gastric Cancermentioning

confidence: 99%

Inflammation, atrophy, and gastric cancer

Fox

Wang²

2007

J. Clin. Invest.

694

626

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“…Immunostaining of BrdU was performed on 3-µm paraffin sections as previously described (Fox et al, 1996) with a mouse anti-BrdU IgG as the primary antibody, a rabbit anti-mouse biotinylated IgG as the secondary antibody, and avidin and biotinylated horseradish peroxidase reagents and diaminobenzidine tetrahydrochloride as enzyme/substrate reagents (Dako, Carpinteria, CA, USA). BrdU labelling index was determined by counting the numbers of positive and the total number of crypt epithelial cells.…”

Section: Brdu Labelling and Cell Countingmentioning

confidence: 99%

Increased expression of HGF and c-met in rat small intestine during recovery from methotrexate-induced mucositis

et al. 2000

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Summary Chemotherapy or radiotherapy often cause mucosal damage in the gut (gut mucositis) in cancer patients. As a step to investigate mechanisms underlying subsequent intestinal repair, we have examined the expression profiles of hepatocyte growth factor (HGF) and its receptor c-met, two molecules previously implicated in tissue repair, in comparison to the histopathological and proliferative changes in a rat model of methotrexate-induced small intestinal mucositis. Histological analysis of the intestinal specimens revealed crypt loss and villus atrophy with damage maximal on day 5 after methotrexate injection, and normalization of mucosal structure commencing on day 6. Crypt cell proliferation was decreased dramatically on day 3, normalized on day 4 and up-regulated on days 5 and 6. HGF and c-met protein/mRNA expression was up-regulated between days 4 and 7, with the mRNA co-localizing to the crypt and lower villus epithelium. Therefore, following methotrexate injection, a decrease in crypt cell proliferation preceded histological damage, and conversely, crypt cell hyperproliferation preceded mucosal regeneration. Up-regulation of HGF and c-met coincided with crypt hyperproliferation and mucosal recovery, suggesting a role for HGF in intestinal repair following acute injury. The crypt epithelial localization of HGF and c-met implies an autocrine or paracrine mechanism of HGF action. All these procedures were approved by the Animal Ethics Committee of the Women's and Children's Hospital, Adelaide, Australia. Histopathological analysis of intestinal damage and repairTransverse sections (4 µm in thickness) of paraffin-embedded proximal jejunal specimens were stained with haematoxylin and eosin (H&E) and examined with a light microscope. A semi-quantitative histological assessment of intestinal damage was utilized to obtain an overall score of damage severity. A total score for the sample was derived from the sum of scores for 11 histopathological criteria as we have previously described (Howarth et al, 1996), including villus fusion and stunting (atrophy), disruption of brush border and surface enterocytes, disappearance of goblet cells, reduction in numbers of mitotic figures, crypt loss/architectural disruption, disruption or distortion of crypt cells, crypt abscess formation, infiltration of polymorphonuclear cells and lymphocytes and dilatation of lymphatics and capillaries. For each criterion, a score was given to represent a mild (score 1), moderate (2), severe (3), or no (0) changes. Quantitative histological analyses were also conducted to measure the changes in crypt depth and villus height in the jejunal specimens over the time course. Microscopic images were acquired and analysed. For each animal, the height and depth of ten villi and crypts respectively were measured at three tissue levels, each separated by 100 µm, and means of the 30 measurements were calculated for each animal. Although histological damage prevented accurate measurements of villus and crypt lengths in some regions, in the jejunal ...

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“…Moreover, lymphoid follicle formation by H. pylori infection was never observed in C57BL/6J mice irrespective of nTx, although these mice developed severe active gastritis by H. pylori infection, which is believed to be a typical Th1-type inflammation (data not shown). [24][25][26] These data suggest that, in contrast to H. pylori-induced active gastritis, both Th1 and Th2 responses are necessary for the development of MALT lymphomalike lesions by H. pylori infection. Supporting this idea, we observed, in addition to IFN-g, expression of IL-4, a representative Th2-type cytokine, in the gastric mucosa of only H. pylori-infected BALB/c mice with nTx that developed lymphoid follicles.…”

Section: Discussionmentioning

confidence: 99%

Immunogenetic analysis of gastric MALT lymphoma-like lesions induced by Helicobacter pylori infection in neonatally thymectomized mice

Fukui

Okazaki

Tamaki

et al. 2004

Laboratory Investigation

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Most gastric mucosa-associated lymphoid tissue (MALT) lymphomas are caused by Helicobacter pylori (H. pylori) infection. We previously reported that acquired lymphoid follicles with germinal centers were induced by H. pylori infection in neonatally thymectomized (nTx) mice. In the present study, we developed gastric MALT lymphoma-like lesions in nTx mice by long-term H. pylori infection, and performed immunogenetic analyses. BALB/c mice were thymectomized on the 3rd day after birth. At 6 weeks of age, mice were orally infected with 10 8 H. pylori and serially killed 2, 4, 6, and 12 months later. Normal BALB/c and noninfected nTx mice served as controls. Follicle formation occurred after 2 months of H. pylori infection in the nTx mice. Follicle formation and infiltration of intraepithelial lymphocytes progressed in a time-dependent manner. Lymphoepithelial lesions, a characteristic feature of MALT lymphoma, also occurred in a time-dependent manner (100% at 12 months). Serum immunoelectrophoresis revealed a monoclonal band (M-protein) in 30% (3/10) of mice 6 months after infection. M-protein-positive mice had amplification of one or two IgM and/or IgG heavy-chain genes in the gastric B lymphocytes, as determined with polymerase chain reaction, suggesting mono-or oligoclonality. Overexpression of Bcl-X L protein was immunohistologically observed in the infiltrating B lymphocytes and in some follicular B lymphocytes in 80% (8/10) of the cases at 12 months. Thus, H. pylori infection is involved in the development of gastric MALT lymphoma-like lesions in nTx mice. Our mouse model is useful for clarifying the pathogenetic mechanism of gastric MALT lymphoma by H. pylori infection.

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Hypertrophic gastropathy in Helicobacter felis-infected wild-type C57BL/6 mice and p53 hemizygous transgenic mice

Cited by 167 publications

References 1 publication

Inflammation, atrophy, and gastric cancer

Inflammation, atrophy, and gastric cancer

Increased expression of HGF and c-met in rat small intestine during recovery from methotrexate-induced mucositis

Immunogenetic analysis of gastric MALT lymphoma-like lesions induced by Helicobacter pylori infection in neonatally thymectomized mice

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