Helicobacter pylori and Epstein-Barr virus infection and the p53 tumour suppressor pathway in gastric stump cancer compared with carcinoma in the non-operated stomach

Baas, Inge O.; Rees, Bastiaan P. van; Musler, Alex R.; Craanen, M. E.; Tytgat, G. N. J.; Berg, F. M. Van Den; Offerhaus, G. Johan A.

doi:10.1136/jcp.51.9.662

Cited by 45 publications

(36 citation statements)

References 31 publications

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“…Given the global annual incidence of >950,000 cases of gastric adenocarcinoma (3) , and the known association of EBV infection with 8%-10% of cases (4) (5) , including 80% of rare lymphoepithelioma-like gastric carcinoma (6) (7) and 35% of stump gastric carcinomas (8) (9) , EBV-positive gastric cancer cases constitute the largest group of EBV-associated malignancies.…”

Section: Introductionmentioning

confidence: 99%

Epstein-Barr virus-positive gastric cancer: a distinct molecular subtype of the disease?

Jácome

Lima

Kazzi

et al. 2016

Rev. Soc. Bras. Med. Trop.

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Approximately 90% of the world population is infected by Epstein-Barr virus (EBV). Usually, it infects B lymphocytes, predisposing them to malignant transformation. Infection of epithelial cells occurs rarely, and it is estimated that about to 10% of gastric cancer patients harbor EBV in their malignant cells. Given that gastric cancer is the third leading cause of cancerrelated mortality worldwide, with a global annual incidence of over 950,000 cases, EBV-positive gastric cancer is the largest group of EBV-associated malignancies. Based on gene expression profile studies, gastric cancer was recently categorized into four subtypes; EBV-positive, microsatellite unstable, genomically stable and chromosomal instability. Together with previous studies, this report provided a more detailed molecular characterization of gastric cancer, demonstrating that EBV-positive gastric cancer is a distinct molecular subtype of the disease, with unique genetic and epigenetic abnormalities, reflected in a specific phenotype. The recognition of characteristic molecular alterations in gastric cancer allows the identification of molecular pathways involved in cell proliferation and survival, with the potential to identify therapeutic targets. These findings highlight the enormous heterogeneity of gastric cancer, and the complex interplay between genetic and epigenetic alterations in the disease, and provide a roadmap to implementation of genome-guided personalized therapy in gastric cancer. The present review discusses the initial studies describing EBV-positive gastric cancer as a distinct clinical entity, presents recently described genetic and epigenetic alterations, and considers potential therapeutic insights derived from the recognition of this new molecular subtype of gastric adenocarcinoma.

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Section: Introductionmentioning

confidence: 99%

Epstein-Barr virus-positive gastric cancer: a distinct molecular subtype of the disease?

Jácome

Lima

Kazzi

et al. 2016

Rev. Soc. Bras. Med. Trop.

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“…The aberrant expression of p21 has been documented in gastric cancer (Baas et al, 1998;Craanen et al, 1999;Baldus et al, 2001). However, the mechanism responsible for its aberrant expression is not clear.…”

Section: Introductionmentioning

confidence: 99%

Upregulation of heme oxygenase-1 and p21 confers resistance to apoptosis in human gastric cancer cells

et al. 2004

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Both heme oxygenase-1 (HO-1) and p21 WAF1/Cip1 (p21) are involved in the pathogenesis of human cancer and their functions are closely associated with apoptosis. However, how these two molecules regulate apoptosis in human gastric cancer is unknown. In this study, we studied how HO-1 and p21 were regulated in two gastric cancer cell lines, MKN-45 with wild p53 and MKN-28 with mutant p53. The cells were treated with hemin and cadmium to induce HO-1. The result showed that HO-1 protein was significantly induced by hemin and cadmium in both cells tested. Following the HO-1 expression, p21 level was also markedly induced. The cells with increased HO-1 and p21 showed obviously resistantance to apoptotic stimuli. The levels of HO-1 and p21 induced were significantly inhibited by p38 mitogen-activated protein kinase (p38 MAPK) inhibitor (SB203580) and extracellular-regulated kinase (ERK) inhibitor (PD098059). Parallel to decreased HO-1 and p21 expression, the kinase inhibitors also significantly attenuated the resistance of the cells to apoptosis. The elevated HO-1 and p21 was further found to be associated with increase activity of the nuclear NFjB and the inhibition of NF-jB led to the block of their induction. The elevated HO-1 and p21 were also demonstrated to be related to increased cellular inhibitor of caspase inbitory protein-2 (c-IAP2) and decreased caspapse-3 activity. It was noted that the above changes observed were not different between MKN-45 and MKN-28 cells, suggesting the functions of HO-1 and p21 were irrespective of the status of p53. In conclusion, we demonstrate that the resistance to apoptosis in gastric cancer cells with elevated HO-1 and p21 is independent of p53 status in a p38 MAPK-and ERK-mediated pathway with elevated c-IAP2 and decreased caspase-3 activity and that this pathway is sensitive to the inhibition of NF-jB.

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“…Studies that evaluated genetics, molecular biology and infection in carcinomas of the stomach operated or not, found differences in relation to infection by H. pylori and Epstein-Barr virus, suggesting that there may be some different etiological factors 2,36 . The study of carcinogenesis in the operated stomach and its etiological factors can lead to clarification of the mechanisms of development and progression of gastric cancer.…”

Section: Discussionmentioning

confidence: 99%

Modelo de carcinogênese gástrica utilizando piloroplastia de Finney: estudo experimental em ratos

Kaminski¹,

Kruel²

2011

ABCD, arq. bras. cir. dig.

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-Background: The duodenogastric reflux has been implicated as a potential carcinogen for the stomach and esophagus and is one of the factors that may explain the development of gastric stump cancer. Experimental models of carcinogenesis in the stomach stump or in the duodenogastric anastomosis are well defined. Aim -To develop an experimental model of gastric carcinogenesis through the Finney pyloroplasty, evaluate the influence of ingestion of sodium nitrite in this model, analyze the concentrations of bile acids and the pH of the stomach. Methods -A hundred and ten Wistar rats were operated and divided into four groups: Group I (15 rats) underwent laparotomy (Sham group); Group II (15 rats) underwent laparotomy (Sham) and ingestion of sodium nitrite in drinking water; Group III (40 rats) submitted to the Finney pyloroplasty and Group IV (40 rats) submitted to the Finney pyloroplasty and ingestion of sodium nitrite in drinking water. After 50 weeks of surgery, the rats were sacrificed and samples collected for analysis of gastric pH, dosing of bile acids and histological analysis. Results -The immediate postoperative mortality was 9%, and during the experiment, 10 rats died. The control group (I) did not show gastric lesions; the control group with sodium nitrite (II) developed papillomas in the pre-stomach in 16.6%; the operated groups with pyloroplasty had adenomas in 10.3% in Group III and 14.2 % in Group IV, and adenocarcinoma in 55.1% in group III and 14.2% in Group IV. The implementation of glands into the submucosa and muscle in the area of anastomosis (mucosa deployment) was not sufficient criterion for deciding on the malignancy of the lesions, requiring the simultaneous presence of atypical cells. The concentration of bile acids in gastric juice was higher in Groups III and IV. The measurement of gastric pH was not different in both groups. Conclusion -1) The Finney pyloroplasty is suitable experimental model of gastric carcinogenesis; 2) it induced duodenogastric reflux; 3) the duodenogastric reflux served as a carcinogen for the stomach; 4) there was no relationship between pH and the development of gastric carcinoma; 5 ) sodium nitrite did not act as a carcinogen for the stomach of rats. ABCDDV/816RESUMO -Racional -O refluxo duodenogástrico tem sido implicado como potencial carcinógeno para o estômago e esôfago e é um dos fatores que podem explicar o desenvolvimento de câncer no coto gástrico. Modelos experimentais de carcinogênese no estômago ressecado ou nas gastrojejunoanastomoses estão bem definidos. Objetivos -Desenvolver um modelo experimental de carcinogênese gástrica através de piloroplastia à Finney, avaliar a influência da ingestão de nitrito de sódio nesse modelo, analisar as concentrações de ácidos biliares e o valor do pH gástrico. Métodos -Foram operados 110 ratos Wistar divididos em quatro grupos: Grupo I (15 ratos) submetidos à laparotomia (grupo Sham); Grupo II (15 ratos) submetidos à laparotomia (Sham) e à ingestão de nitrito de sódio na água de beber; Grupo III (40 ratos...

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Helicobacter pylori and Epstein-Barr virus infection and the p53 tumour suppressor pathway in gastric stump cancer compared with carcinoma in the non-operated stomach

Cited by 45 publications

References 31 publications

Epstein-Barr virus-positive gastric cancer: a distinct molecular subtype of the disease?

Epstein-Barr virus-positive gastric cancer: a distinct molecular subtype of the disease?

Upregulation of heme oxygenase-1 and p21 confers resistance to apoptosis in human gastric cancer cells

Modelo de carcinogênese gástrica utilizando piloroplastia de Finney: estudo experimental em ratos

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