Involvement of oxidative stress in experimentally induced reflux esophagitis and Barrett’s esophagus: clue for the chemoprevention of esophageal carcinoma by antioxidants

Lee, Jeong Sang; Oh, Tae Young; Ahn, Byung Ok; Cho, Hyeon; Kim, Won; Kim, Young Bae; Surh, Young Joon; Kim, Hun Jong; Hahm, Ki Baik

doi:10.1016/s0027-5107(01)00199-3

Cited by 97 publications

(79 citation statements)

References 28 publications

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“…The first one is that both are consequence of oxidative damage. Several lines of evidence indicate that oxidative stress plays a causal role in the development of Barrett's esophagus and in its progression to esophageal adenocarcinoma: (a) oxidative damage was increased in the esophagus of rats with induced esophageal adenocarcinoma (38) and rats with induced reflux esophagitis (39,40); (b) Barrett's esophagus mucosa shows increased levels of reactive oxygen species (17) and DNA adducts (41), and decreased antioxidant capacity (42); and (c) higher intakes of antioxidants (43) and use of NSAID (14) are associated with decreased risk of esophageal adenocarcinoma. Oxidative stress is also one major cause of telomere shortening because single-strand breaks formed by oxidative or alkylative DNA damage are not repaired well in telomeres (1).…”

Section: Discussionmentioning

confidence: 99%

Leukocyte Telomere Length Predicts Cancer Risk in Barrett's Esophagus

Risques¹,

Vaughan

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

137

111

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Purpose: Leukocyte telomere length has gained attention as a marker of oxidative damage and age-related diseases, including cancer. We hypothesize that leukocyte telomere length might be able to predict future risk of cancer and examined this in a cohort of patients with Barrett's esophagus, who are at increased risk of esophageal adenocarcinoma and thus were enrolled in a long-term cancer surveillance program. Patients and Methods: In this prospective study, telomere length was measured by quantitative PCR in baseline blood samples in a cohort of 300 patients with Barrett's esophagus followed for a mean of 5.8 years. Leukocyte telomere length hazard ratios (HR) for risk of esophageal adenocarcinoma were calculated using multivariate Cox models. Results: Shorter telomeres were associated with increased esophageal adenocarcinoma risk (age-adjusted HR between top and bottom quartiles of telomere length, 3.45; 95% confidence interval, 1.35-8.78; P = 0.009). This association was still significant when individually or simultaneously adjusted for age, gender, nonsteroidal anti-inflammatory drug (NSAID) use, cigarette smoking, and waist-to-hip ratio (HR, 4.18; 95% confidence interval, 1.60-10.94; P = 0.004). The relationship between telomere length and cancer risk was particularly strong among NSAID nonusers, ever smokers, and patients with low waist-to-hip ratio. Conclusion: Leukocyte telomere length predicts risk of esophageal adenocarcinoma in patients with Barrett's esophagus independently of smoking, obesity, and NSAID use. These results show the ability of leukocyte telomere length to predict the risk of future cancer and suggest that it might also have predictive value in other cancers arising in a setting of chronic inflammation. (Cancer Epidemiol Biomarkers Prev 2007;16(12):2649-55)

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Section: Discussionmentioning

confidence: 99%

Leukocyte Telomere Length Predicts Cancer Risk in Barrett's Esophagus

Risques¹,

Vaughan

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

137

111

View full text Add to dashboard Cite

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“…These findings are likely related to the chronic cycles of epithelial regeneration in an environment of chemical damage and inflammation in Barrett's esophagus. These factors promote oxidative damage in Barrett's esophagus (39,40) and telomere attrition is accelerated by oxidative injury as well as cell proliferation (41,42). Telomerase activity has been observed to be present at very low levels in the mucosa of Barrett's esophagus, increasing in activity in dysplastic Barrett's esophagus mucosa and cancer (43); it thus seems that that low levels of telomerase expression in metaplastic Barrett's esophagus epithelium are unable to counterbalance telomere attrition but that increasing telomerase expression with increasing histologic grade allows the increasing telomere length with grade that we observe.…”

Section: Discussionmentioning

confidence: 99%

Chromosomal Instability in Barrett's Esophagus Is Related to Telomere Shortening

Finley¹,

Reid

Odze

et al. 2006

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Barrett's esophagus is a useful model for the study of carcinogenesis, as the metaplastic columnar epithelium that replaces squamous esophageal epithelium is at elevated risk for development of adenocarcinoma. We examined telomere length and chromosomal instability (CIN) in Barrett's esophagus biopsies using fluorescence in situ hybridization. To study CIN, we selected centromere and locus-specific arm probes to chromosomes 17/17p (p53), 11/11q (cyclin D1), and 9/9p (p16 INK4A), loci reported to be involved in early stages of Barrett's esophagus neoplasia. Telomere shortening was observed in Barrett's esophagus epithelium at all histologic grades, whereas CIN was highest in biopsies with dysplastic changes; there was, however, considerable heterogeneity between patients in each variable. Alterations on chromosome 17 were strongly correlated with telomere length (r = 0.55; P < 0.0001) and loss of the 17p arm signal was the most common event. CIN on chromosome 11 was also associated with telomere shortening (r =0.3; P = 0.05), although 11q arm gains were most common. On chromosome 9p, arm losses were the most common finding, but chromosome 9 CIN was not strongly correlated with telomere length. We conclude that CIN is related to telomere shortening in Barrett's esophagus but varies by chromosome. Whether instability is manifested as loss or gain seems to be influenced by the chromosomal loci involved. Because telomere shortening and CIN are early events in Barrett's esophagus neoplastic progression and are highly variable among patients, it will be important to determine whether they identify a subset of patients that is at risk for more rapid neoplastic evolution. (Cancer Epidemiol Biomarkers Prev 2006;15(8):1451-7)

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“…Constitutive NF-B activation has been shown to be associated with squamous proliferation and tumor growth (27) and resistance to apoptosis (53). Drugs that inhibit NF-B may serve as potential therapeutic agents in these abnormal proliferative processes (52)(53)(54)(55). Antioxidants (56), phytochemicals (57), and antiinflammatory mediators (58) may exert some of their antiproliferative functions through suppression of NF-B.…”

Section: Discussionmentioning

confidence: 99%

Pseudomonas aeruginosaLipopolysaccharide Induction of Keratinocyte Proliferation, NF-κB, and Cyclin D1 Is Inhibited by Indomethacin

Preciado

Caicedo

Jhanjee

et al. 2005

The Journal of Immunology

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NF-κB is activated during acute inflammatory states as well as in other injury response disease states. Several pathologic states in squamous tissue injury response are characterized by increased squamous proliferation. This study was performed to investigate the hypothesis that Pseudomonas aeruginosa LPS is able to activate a proliferative phenotype in squamous cells via NF-κB induction and that this NF-κB-mediated response may be abrogated with the classic anti-inflammatory agent indomethacin. EMSA, luciferase reporter gene experiments, Western blots, and cellular proliferation assays were performed in normal and transformed human keratinocytes after stimulation with P. aeruginosa LPS. EMSA and luciferase reporter gene assays showed a 3- to 5-fold induction of active NF-κB in human keratinocyte cell lines after stimulation with P. aeruginosa LPS. The stimulation correlated with significantly increased cellular proliferation. As one potential mechanism for this increase in proliferation, an NF-κB-specific activation of cyclin D1 was observed. Both the NF-κB induction and proliferation response were inhibited with indomethacin and in dominant negative stable transfection clones. P. aeruginosa LPS activates proliferation of human keratinocytes, potentially through the induction of NF-κB and cyclin D1. These findings suggest that bacterial components can contribute to proliferative disease states in squamous epithelium through NF-κB activation.

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Involvement of oxidative stress in experimentally induced reflux esophagitis and Barrett’s esophagus: clue for the chemoprevention of esophageal carcinoma by antioxidants

Cited by 97 publications

References 28 publications

Leukocyte Telomere Length Predicts Cancer Risk in Barrett's Esophagus

Leukocyte Telomere Length Predicts Cancer Risk in Barrett's Esophagus

Chromosomal Instability in Barrett's Esophagus Is Related to Telomere Shortening

Pseudomonas aeruginosaLipopolysaccharide Induction of Keratinocyte Proliferation, NF-κB, and Cyclin D1 Is Inhibited by Indomethacin

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