Infection, Inflammation, and Gastrointestinal Cancer

Boland, C. Richard

doi:10.1136/gut.2004.060079

Cited by 83 publications

(65 citation statements)

References 82 publications

(58 reference statements)

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“…Taking cues from the potential involvement of JCV in a subset of gastro-intestinal tumors 35,36 in this study we determined the prevalence of polyomaviruses JCV, BKV and SV40 in Tunisian patients with gastric carcinomas. Findings were analyzed in relation to clinical, pathologic, molecular features of gastric cancers and patient survival.…”

Section: Discussionmentioning

confidence: 99%

The presence of JC virus in gastric carcinomas correlates with patient's age, intestinal histological type and aberrant methylation of tumor suppressor genes

et al. 2010

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JC virus (JCV) is a neurotropic polyomavirus and the causative agent of progressive multifocal leukoencephalopathy. A role for JCV in gastrointestinal malignancies has been recently suggested. This study was carried out to determine the prevalence of polyomaviruses including JCV, BKV and SV40 in gastric cancers in Tunisia and to determine the clinicopathological characteristics of virus-associated gastric carcinomas. The presence of polyomaviruses DNA sequences was surveyed in 61 cases of primary gastric carcinomas and in 53 paired non-tumor gastric mucosa by PCR. Findings were correlated to clinicopathological parameters, p53 expression and methylation status of 11 tumor-related genes. Using PCR assays, JCV T-antigen sequence was more frequently detected in gastric carcinomas than in non-tumor gastric mucosa (26 vs 6%, P ¼ 0.03), while those of SV40 and BKV were not detected in any cases. Correlation analysis showed that JCV had higher frequency in patients older than 55 years (P ¼ 0.034) and in the intestinal histological type (P ¼ 0.04). With regard to methylation status, P16 and P14 showed significantly higher methylation frequencies in JCV-positive gastric carcinomas than in JCV-negative cases (P ¼ 0.007 and P ¼ 0.003, respectively). Moreover, the mean of the methylation index was significantly higher in JCV-positive than in JCV-negative cases (P ¼ 0.024). In multivariate logistic regression analysis, age of patients and the methylation index are only the two independent factors associated with JCV infection. Kaplan-Meier survival analysis showed a trend toward better survival for JCV-associated gastric carcinomas patients (log-rank, P ¼ 0.11). Our study suggests a role of JCV as cofactor in the pathogenesis of the intestinal type of gastric carcinomas in older persons.

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Section: Discussionmentioning

confidence: 99%

The presence of JC virus in gastric carcinomas correlates with patient's age, intestinal histological type and aberrant methylation of tumor suppressor genes

et al. 2010

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“…The prevalence of ulcerative colitis in Western societies has been estimated to be 0.3% and these individuals face an increasing risk of colorectal cancer development as the duration of their disease increases. 7,50 Therefore, the development of chemoprevention strategies against colitis-associated colorectal cancer and other inflammation-mediated cancers is strongly warranted. Previous studies have already confirmed the efficacy of small molecule activators of Nrf2 signaling in the prevention of electrophile-induced chemical carcinogenesis.…”

Section: Discussionmentioning

confidence: 99%

Increased colonic inflammatory injury and formation of aberrant crypt foci in Nrf2‐deficient mice upon dextran sulfate treatment

Osburn

Karim

Dolan

et al. 2007

Intl Journal of Cancer

171

118

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Chronic inflammation has been associated with increased risk of developing cancer. The transcription factor NF-E2-related factor 2 (Nrf2) controls the expression of numerous antioxidative enzymes that have been shown to attenuate acute inflammation. The present study investigated the role of Nrf2 genotype in modulating inflammation-promoted colorectal tumorigenesis. Nrf2 wild-type (WT) and Nrf2-deficient (N0) mice were administered a single dose of azoxymethane followed by a 1-week dose of drinking water with or without 1% dextran sulfate sodium (DSS). Aberrant crypt foci were counted 3 weeks after the cessation of DSS treatment. DSS treatment significantly increased numbers of aberrant crypt foci in N0 mice, but not WT mice. The extent of inflammation over the course of DSS treatment was analyzed in both genotypes. Histological analysis of colon sections revealed that N0 mice had markedly increased inflammation and mucosal damage when compared to WT mice beginning on Day 6 of DSS treatment. Although similar levels of inflammatory and oxidative damage biomarkers were evident in colons from WT and N0 mice at the start of DSS treatment, increased colonic proinflammatory cytokine mRNA transcript levels, myeloperoxidase activity and 3-nitrotyrosine immunoreactivity were observed on Day 6 of DSS treatment in N0 mice, but not WT mice. Additionally, DSS treatment resulted in increased lipid peroxidation and loss of aconitase activity in N0 mice, but not WT mice, reflecting increased oxidative damage in colons from N0 mice. Taken together, these results clearly illustrate the role of Nrf2 in regulating an adaptive response that protects against early-phase inflammation-mediated tumorigenesis. ' 2007 Wiley-Liss, Inc.

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“…6 SSBs are found in the healthy colon but are increased with inflammation or certain dietary agents. 7,8 Therefore, efficient repair of both types of DNA damage is important in the protection against proliferation of damaged cells. On the other hand, impaired DNA damage response is a major determinant of radiotherapy and cytotoxic drug responsiveness of cancer cells.…”

Section: Introductionmentioning

confidence: 99%

The "Mutated in Colorectal Cancer" Protein Is a Novel Target of the UV-Induced DNA Damage Checkpoint

et al. 2010

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MCC is a potential tumor suppressor gene, which is silenced by promoter hypermethylation in a subset of colorectal cancers. However, its functions have remained poorly understood. In the present study, we describe a novel function of MCC in the DNA damage response. Several novel phosphorylation sites were identified by mass spectrometry, including 2 highly conserved ATM/ATR consensus sites at serine 118 and serine 120. In addition, exposure to ultraviolet radiation (UV), but not phleomycin, caused PI3K-dependent phosphorylation of MCC and its nuclear localization. Re-expression of MCC in HCT15 colorectal cancer cells led to a G2/M arrest, and MCC knockdown impaired the induction of a G2/M arrest following UV radiation. Finally, mutation of S118/120 to alanine did not affect MCC nuclear shuttling following UV but did impair MCC G2/M checkpoint activity. Thus, these results suggest that MCC is a novel target of the DNA damage checkpoint and that MCC is required for the complete cell cycle arrest in the G2/M phase in response to UV.

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Infection, Inflammation, and Gastrointestinal Cancer

Cited by 83 publications

References 82 publications

The presence of JC virus in gastric carcinomas correlates with patient's age, intestinal histological type and aberrant methylation of tumor suppressor genes

The presence of JC virus in gastric carcinomas correlates with patient's age, intestinal histological type and aberrant methylation of tumor suppressor genes

Increased colonic inflammatory injury and formation of aberrant crypt foci in Nrf2‐deficient mice upon dextran sulfate treatment

The "Mutated in Colorectal Cancer" Protein Is a Novel Target of the UV-Induced DNA Damage Checkpoint

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