Cyclo‐oxygenase‐2 expression in Barrett's oesophageal carcinogenesis: an immunohistochemical study

Cheong, Edward; Igali, Laszlo; Harvey, Ian; Mole, M.; Lund, Elizabeth K.; Johnson, Ian T.; Rhodes, Michael

doi:10.1046/j.1365-2036.2003.01432.x

Cited by 27 publications

(23 citation statements)

References 40 publications

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“…Considerable data have implicated COX-2 in BO and OAC: COX-2 expression increases in BO with the development of dysplasia and cancer (Cheong et al 2003), COX-2 inhibitors reduce proliferation and induce apoptosis in OAC cell lines in culture (Buttar et al 2002a) and COX-2 inhibitors reduce progression in animal models of BO (Buttar et al 2002b). However, the expression of COX-2 and prevention of disease by COX-2 inhibitors are not universal and factors such as G-Gly driving the avoidance of apoptosis by alternative pathways could contribute to progression of cancer.…”

Section: Discussionmentioning

confidence: 99%

Glycine-extended gastrin inhibits apoptosis in Barrett's oesophageal and oesophageal adenocarcinoma cells through JAK2/STAT3 activation

Beales

Ogunwobi²

2009

Journal of Molecular Endocrinology

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Barrett's oesophagus (BO) and oesophageal adenocarcinoma (OAC) are regarded as complications of gastrooesophageal reflux disease, although all the factors that contribute to the development of these lesions are unknown. Acid suppressive drugs are widely used for symptomatic therapy of reflux disease but may induce hypersecretion of gastrin peptides. Amidated gastrin (G-17) has been shown to be a growth factor for OAC cells. We have examined the effects of glycine-extended gastrin (G-Gly), an alternative product of progastrin processing on apoptosis in the QhERT Barrett's oesophageal cell line and OE33 and BIC-1 OAC cells. G-Gly inhibited serum-starvation and camptothecininduced apoptosis in all three cell lines, G-17 was only effective in OE33 cells. By contrast to the effects of G-17, the antiapoptotic effect of G-Gly was independent of both the CCK 2 receptor and cyclo-oxygenase-2 activity. G-Gly stimulated JAK2 phosphorylation and kinase activity and JAK2-dependent STAT3 phosphorylation and transcriptional activity. G-Gly also increased mRNA and protein levels of the anti-apoptotic proteins survivin and BCL2L1 but did not affect the levels of BAD, BAX or BCL-2. Novel small molecule inhibitors of JAK2 and STAT3 as well as STAT3 siRNA blocked the anti-apoptotic effects of G-Gly and inhibited the induction of survivin and BCL2L1 in OE33 cells. We conclude that G-Gly inhibits apoptosis in BO and OAC via mechanisms distinct from those activated by G-17 and involving JAK2 and STAT3 activation. Release of gastrin peptides in response to acid suppressive therapy may adversely influence the dynamics of the epithelium in BO.

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Section: Discussionmentioning

confidence: 99%

Glycine-extended gastrin inhibits apoptosis in Barrett's oesophageal and oesophageal adenocarcinoma cells through JAK2/STAT3 activation

Beales

Ogunwobi²

2009

Journal of Molecular Endocrinology

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“…Of these, doctors refused contact with 71 patients and 167 died before consent could be obtained. Patients who were too ill (91), were mentally incapable (23), could not read or write in English (41), or could not be contacted (26) were excluded. The remaining 1,191 patients were invited to participate, and, of these, 928 (78% of those approached) agreed to take part.…”

Section: Methodsmentioning

confidence: 99%

“…This class of medications inhibits the activity of the cyclooxygenase (COX) enzymes (both constitutional COX-1 and inducible COX-2 isoenzymes). COX-2 is overexpressed in many epithelial cancers, including esophageal cancers (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37). With regard to tumor growth, COX-2 enzyme functions to reduce cellular adhesion and apoptosis and increase angiogenesis (38)(39)(40).…”

Section: Introductionmentioning

confidence: 99%

Aspirin, Nonsteroidal Anti-inflammatory Drugs, and the Risks of Cancers of the Esophagus

Sadeghi

Bain

Pandeya

et al. 2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Frequent consumption of aspirin and nonsteroidal anti-inflammatory drugs (NSAID) has been associated with reduced occurrence of cancers of the esophagus, although potential modifying effects of other causal factors remain relatively unexplored. Methods: We compared nationwide samples of Australian patients with adenocarcinomas of the esophagus (EAC; n = 367) or esophagogastric junction (EGJAC; n = 426) or esophageal squamous cell carcinoma (ESCC; n = 309) with control participants sampled from a population register (n = 1,580). Intakes of aspirin, other NSAIDs, and acetaminophen (paracetamol) were assessed from self-reports. We calculated odds ratios (OR) and 95% confidence intervals (95% CI) using multivariable logistic regression. Results: Compared with never-users of aspirin, those who used aspirin at least weekly had significantly lower risks of EAC (OR, 0.48; 95% CI, 0.32-0.72), EGJAC (OR, 0.71; 95% CI, 0.49-1.01), and ESCC (OR, 0.63; 95%

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“…Experimentally statins inhibit proliferation and induce apoptosis in Barrett's cell lines and these effects are enhanced in an additive manner in combination with inhibition of the cyclo-oxygenase-2 pathway (10,11). Over-expression of COX-2 in Barrett's mucosa has been reported, and experimentally (34), and in clinical studies beneficial effects of COX-inhibitors on progression to cancer have been reported (13,16,(35)(36)(37). Thus it is possible that statin and aspirin impair survival of the Barrett's clone at a very early stage and so impair establishment of a mature Barrett's segment.…”

Section: Discussionmentioning

confidence: 99%

Reduced Risk of Barrett’s Esophagus in Statin Users: Case–Control Study and Meta-Analysis

et al. 2015

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Cyclo‐oxygenase‐2 expression in Barrett's oesophageal carcinogenesis: an immunohistochemical study

Cited by 27 publications

References 40 publications

Glycine-extended gastrin inhibits apoptosis in Barrett's oesophageal and oesophageal adenocarcinoma cells through JAK2/STAT3 activation

Glycine-extended gastrin inhibits apoptosis in Barrett's oesophageal and oesophageal adenocarcinoma cells through JAK2/STAT3 activation

Aspirin, Nonsteroidal Anti-inflammatory Drugs, and the Risks of Cancers of the Esophagus

Reduced Risk of Barrett’s Esophagus in Statin Users: Case–Control Study and Meta-Analysis

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