cagA+ Helicobacter pylori induces greater levels of prostaglandin E2 than cagA− strains

Al-Marhoon, Mohammed S.; Nunn, Sheila; Soames, Roger

doi:10.1016/j.prostaglandins.2004.01.007

Cited by 11 publications

(5 citation statements)

References 24 publications

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“…The PGE 2 level significantly increases in gastric cancer, ( 25 ) and the level is associated with the H. pylori infection status. ( 26 )…”

Section: Induction Of the Cox‐2/pge2 Pathway In Gastric Cancermentioning

confidence: 99%

“…The PGE 2 level significantly increases in gastric cancer, (25) and the level is associated with the H. pylori infection status. (26) Gastric tumor development in mouse and rat models induced by chemical carcinogens or Helicobacter infection is suppressed by treatment with NSAIDs or COXIBs. (27)(28)(29) H. pylori infection in Mongolian gerbils induces gastric tumorigenesis, which is quite similar to the course of human gastric carcinogenesis.…”

Section: Induction Of the Cox-2/pge 2 Pathway In Gastric Cancermentioning

confidence: 99%

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Prostaglandin E₂, Wnt, and BMP in gastric tumor mouse models

Oshima

Oguma

et al. 2009

Cancer Science

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The development of gastric cancer is closely associated withE pidemiological studies indicate that the regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) lowers the mortality rate of gastrointestinal cancer.(1) The major target of NSAIDs is cyclooxygenases (COXs), COX-1 and COX-2, which are rate-limiting enzymes for prostaglandin biosynthesis (Fig. 1). COX-1 is constitutively expressed in most tissues and it is considered to be responsible for physiological levels of prostaglandin.(2) In contrast, COX-2 is induced in inflammation by various stimuli including cytokines and growth factors. The induction of COX-2 expression is also found in a variety of cancer tissues. Mouse genetic studies have demonstrated that disruption of the Ptgs2 gene encoding COX-2 results in the suppression of tumor development in the intestine and skin. (6,7) Moreover, various animal studies have confirmed that treatment with NSAIDs or COX-2 selective inhibitors (COXIBs) suppressed chemically induced tumor formation and xenografted tumor growth.(8) These results, taken together, indicate that the COX-2 pathway plays an essential role in cancer development.However, the mechanism of the COX-2 pathway underlying gastric tumorigenesis has not yet been fully elucidated. To investigate the possible crosstalk between the COX-2 pathway and oncogenic activation in gastric carcinogenesis, a series of mouse models have been constructed and examined as discussed in this review. Induction of the COX-2/PGE 2 pathway in gastric cancerRegular use of NSAIDs is associated with a decreased incidence of gastric cancer.(9-12) Induction of COX-2 is found in approximately 70% of gastric cancer, whereas the expression of COX-1 is not elevated. (13,14) Gastric cancer can be divided into two histological subtypes: intestinal and diffuse types, and the expression of COX-2 is found predominantly in the intestinal-type gastric cancer.(15) These results suggest that the COX-2 pathway plays a role in the development of intestinal-type gastric cancer. Infection with Helicobacter pylori (H. pylori) causes chronic gastritis, which is associated with gastric carcinogenesis.(16) The expression of COX-2 is significantly induced in the H. pyloriinfected gastric mucosa, and that COX-2 expression is suppressed by the eradication of H. pylori.(17) Although the molecular mechanism for COX-2 induction in tumors has not been elucidated, it is possible that the cytokine network is activated by infection and induces the expression of COX-2. H. pylori can stimulate Toll-like receptors (TLRs), leading to activation of the nuclear factor-κB (NF-κB) pathway that induces the expression of COX-2 (Fig. 1). (18,19) Moreover, TLR2/ TLR9 signaling by H. pylori activates mitogen activated protein kinases (MAPK) including p38, resulting in the activation of CRE and AP-1 elements on the COX-2 gene promoter. (19,20) Microsomal PGE synthase-1 (mPGES-1), a PGE 2 converting enzyme is functionally coupled with COX-2.(21) Simultaneous induction of COX-2 and mPGES-1 is observed in gastric canc...

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“…The PGE 2 level significantly increases in gastric cancer, ( 25 ) and the level is associated with the H. pylori infection status. ( 26 )…”

Section: Induction Of the Cox‐2/pge2 Pathway In Gastric Cancermentioning

confidence: 99%

Section: Induction Of the Cox-2/pge 2 Pathway In Gastric Cancermentioning

confidence: 99%

Prostaglandin E₂, Wnt, and BMP in gastric tumor mouse models

Oshima

Oguma

et al. 2009

Cancer Science

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“…1). 50–53 Consistently, the PGE 2 level is found to be significantly increased in gastric cancer, 47 and the COX‐2 and PGE 2 level is associated with the H. pylori infection status, 54,55 indicating that H. pylori infection causes induction of the PGE 2 pathway (Fig. 1).…”

Section: Induction Of Pge2 Pathway In Gastric Mucosamentioning

confidence: 76%

Mouse models of gastric tumors: Wnt activation and PGE2 induction

Oshima

2010

Pathology International

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Accumulating evidence has suggested that cooperation of oncogenic activation and the host responses is important for cancer development. In gastric cancer, activation of Wnt signaling appears to be a major oncogenic pathway that causes tumorigenesis. In the chronic gastritis caused by Helicobacter pylori infection, cyclooxigenase-2 induces prostaglandin E2 (PGE2) biosythesis, which plays an important role in tumorigenesis. We constructed a series of mouse models and investigated the role of each pathway in the gastric tumorigenesis. Wnt activation in gastric epithelial cells suppresses differentiation, and induces development of preneoplastic lesions. On the other hand, induction of the PGE2 pathway in gastric mucosa induces development of spasmolytic polypeptide-expressing metaplasia (SPEM), which is a possible preneoplastic metaplasia. Importantly, simultaneous activation of Wnt and PGE2 pathways leads to dysplastic gastric tumor development. Moreover, induction of the PGE2 pathway also promotes gastric hamartoma development when bone morphogenetic protein (BMP) signaling is suppressed. These results indicate that alteration in the Wnt or BMP signaling impairs epithelial differentiation, and the PGE2 pathway accelerates tumor formation regardless of the types of oncogenic pathways. We review the phenotypes and gene expression profiles of the respective models, and discuss the cooperation of oncogenic pathways and host responses in gastric tumorigenesis. Key words: gastric cancer, mouse model, PGE2, WntGastric cancer is the second most common cause of cancerrelated death worldwide.1 Infection with Helicobacter pylori is associated with gastric cancer development, and the International Agency for Research on Cancer (IARC) classified Helicobacter pylori as a class I carcinogen.2 Accumulating evidence has indicated that chronic inflammatory response associated with infectious disease is a critical component of tumor development. 3 Moreover, it has been shown that infections are responsible for more than 15% of all malignant cancers worldwide, including the association between H. pylori infection and gastric cancer. 4 Notably, host genetic variants in cytokine genes are related to responsiveness to H. pylori infection and the susceptibility to gastric cancer development.5-7 Specific polymorphisms of interleukin (IL)-1b, an important inflammatory cytokine and a potent inhibitor of gastric acid secretion, contribute to intestinal-type gastric cancer progression.8 Polymorphisms in tumor necrosis factor (TNF)-a, IL-1 receptor antagonist, and IL-10 also influence gastric cancer development, [8][9][10] while polymorphisms in the IL-8 promoter have been linked to diffuse-type gastric cancer.11 These results suggest that the response of the host cytokine network to H. pylori infection is an important factor for gastric cancer development.On the other hand, several somatic alterations that activate oncogenic pathways have been identified in human gastric cancer. For example, allelic loss or mutations in p53 are detected in ...

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“…Moreover, the gut bacterium Helicobacter pylori (H. pylori) secretes the CagA toxin, which might amplify the effects of estrogen in diffuse GC [29]. The association between ER, H. pylori infection, and CagA toxin may also contribute to the etiology of diffuse GC, which is more common in younger females [32][33][34][35]. As females aged 40 or younger might not have benefited from these protective factors, the survival rates of males and females in younger groups of patients are essentially equivalent.…”

Section: Discussionmentioning

confidence: 99%

Gender Differences in Patients with Gastric Adenocarcinoma

Xing,

Hosaka,

Moki

et al. 2024

JCM

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Background: Gastric cancer (GC) epidemiology and outcomes vary by gender. Methods: We reviewed 18,436 GC patients from 2008 to 2018 and looked for gender differences in clinical characteristics and survival. Results: The gender proportion was 71% male and 29% female. Males had a significantly (p < 0.001) higher proportion of differentiated GC (66.3%) and a lower proportion of undifferentiated GC (26.3%). Diagnosis through medical check-ups was more common in males (30.0% vs. 26.4%, p < 0.001). Clinical staging revealed 54.6% of males and 52.9% of females had localized disease without lymph node metastasis (LNM), while distant metastasis occurred in 17.4% of males and 16.9% of females (p < 0.001). Kaplan–Meier survival curves indicated females had a significantly higher overall survival (p = 0.0018). The survival advantage for females was evident in the early stages, with a significant difference in localized disease without LNM (p < 0.001) and localized disease with LNM (p = 0.0026, log-rank test) but not in the advanced stages. Multivariate Cox regression analysis showed a significantly reduced mortality risk in females (p < 0.001). Conclusions: Significant gender differences exist with regard to pathological type, presentation, clinical stage, and overall survival. These findings suggest gender-specific strategies for screening, diagnosis, and treatment.

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cagA+ Helicobacter pylori induces greater levels of prostaglandin E2 than cagA− strains

Cited by 11 publications

References 24 publications

Prostaglandin E₂, Wnt, and BMP in gastric tumor mouse models

Prostaglandin E₂, Wnt, and BMP in gastric tumor mouse models

Mouse models of gastric tumors: Wnt activation and PGE2 induction

Gender Differences in Patients with Gastric Adenocarcinoma

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cagA+ Helicobacter pylori induces greater levels of prostaglandin E2 than cagA− strains

Cited by 11 publications

References 24 publications

Prostaglandin E2, Wnt, and BMP in gastric tumor mouse models

Prostaglandin E2, Wnt, and BMP in gastric tumor mouse models

Mouse models of gastric tumors: Wnt activation and PGE2 induction

Gender Differences in Patients with Gastric Adenocarcinoma

Contact Info

Product

Resources

About

Prostaglandin E₂, Wnt, and BMP in gastric tumor mouse models

Prostaglandin E₂, Wnt, and BMP in gastric tumor mouse models