Chemoprevention of esophageal adenocarcinoma by COX-2 inhibitors in an animal model of Barrett's esophagus

Buttar, Navtej; Wang, Kenneth K.; Leontovich, Olga; Westcott, Jay Y.; Pacifico, Rodney J.; Anderson, Marlys; Krishnadath, Krishnawatie K.; Lutzke, Lori S.; Burgart, Lawrence J.

doi:10.1053/gast.2002.32371

Cited by 330 publications

(245 citation statements)

References 33 publications

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“…Reactive oxygen species may cause DNA strand breaks, DNA base modification, lipid peroxidation and protein oxidation (Hyun et al, 2004). Arachidonic acid metabolism and reactive oxygen species together stimulate the growth of BE epithelium, provoke growth and disordered metabolism, and alter gene expression and cell cycle control (Buttar et al, 2002;Chen et al, 2002). These biologic tendencies are in agreement with our current microarray findings in these epithelia.…”

Section: Discussionsupporting

confidence: 89%

Transcriptional profiling suggests that Barrett's metaplasia is an early intermediate stage in esophageal adenocarcinogenesis

Wang

Zhan

Yin³

et al. 2006

Oncogene

112

106

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To investigate the relationship between Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC), we determined gene expression profiles of discrete pathological stages of esophageal neoplasia using a sequence-verified human cDNA microarray. Fifty one RNAs, comprising 24 normal esophagi (NE), 18 BEs, and nine EACs were hybridized to cDNA microarrays. Five statistical analyses were used for the data analysis. Genes showing significantly different expression levels among the three sample groups were identified. Genes were grouped into functional categories based on the Gene Ontology Consortium. Surprisingly, the expression pattern of BE was significantly more similar to EAC than to NE, notwithstanding the known histopathologic differences between BE and EAC. The pattern of NE was clearly distinct from that of EAC. Thirty-six genes were the most differentially modulated, according to these microarray data, in BE-associated neoplastic progression. Twelve genes were significantly differentially expressed in cancer-associated BE's plus EAC (as a single combined tissue group) vs noncancer-associated BE's. These genes represent potential biomarkers to diagnose EAC at its early stages. Our results demonstrate that molecular events at the transcriptional level in BE are remarkably similar to BE's-associated adenocarcinoma of the esophagus. This finding alarmingly implies that BE is biologically closer to cancer than to normal esophagus, and that the cancer risk of BE is perhaps higher than we had imagined. These findings suggest that changes modulated at the molecular biologic level supervene earlier than histologic changes, and that BE is an early intermediate stage in the process of EAC.

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Section: Discussionsupporting

confidence: 89%

Transcriptional profiling suggests that Barrett's metaplasia is an early intermediate stage in esophageal adenocarcinogenesis

Wang

Zhan

Yin³

et al. 2006

Oncogene

112

106

View full text Add to dashboard Cite

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“…34 Experimental animal studies suggest that aspirin and other NSAIDs, with COX-2 inhibitor properties, may prevent both initiation of new esophageal cancer and progression of the established ones. [35][36][37][38][39][40] One previous cohort study found that aspirin use was associated with reduced risk of death among esophageal cancer cases. 41 Although many studies have investigated the effect of NSAID/aspirin use on the risk of developing esophageal cancer in humans, 25,[42][43][44][45][46][47][48][49][50][51][52] results have been inconsistent.…”

mentioning

confidence: 99%

Regular aspirin use and esophageal cancer risk

Jayaprakash

Menezes

Javle

et al. 2006

Intl Journal of Cancer

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Given the high mortality rate and the rapidly increasing incidence rate of esophageal carcinoma, chemopreventive agents are highly desirable. Aspirin has been shown to be associated with reduced risk of developing colorectal carcinoma and other cancers. Even though previous studies have shown reduced risk of esophageal cancer associated with aspirin use, results were inconsistent with respect to frequency and duration of use. In this hospital-based case-control study, 163 esophageal cancer cases were compared to 482 age-and sex-matched hospital controls with nonneoplastic conditions. Participants were classified as regular aspirin users if they had taken the drug at least once a week for 6 months. Results suggest that esophageal cancer risk is significantly lower for regular aspirin users compared to nonusers [adjusted odds ratio (aOR) 0.54; 95% confidence interval (CI) 0.36-0.86]. Individuals who used an equivalent of at least 1 aspirin a day ( 7 tablets/week) were half as likely to have been diagnosed with esophageal carcinoma (aOR 0.47; 95% CI 0.26-0.85), and a linear trend was noted with increasing frequency of use (p trend 0.007). Similar protective effects were noted with 20 years of use, whereas no risk reduction was noted with >20 years of use. Consistent reduction in risk associated with aspirin use was noted among both the major histological subtypes, but the protective effect appears to be more pronounced in adenocarcinoma compared to squamous cell carcinoma. Overall, results from the current study suggest that regular aspirin use may be associated with reduced risk of esophageal cancer. ' 2006 Wiley-Liss, Inc.Key words: aspirin; esophageal cancer; histology; chemoprevention; epidemiology The American Cancer Society has estimated that 14,520 new cases of esophageal carcinoma will be diagnosed in the United States (US) in 2005. 1 Worldwide, esophageal carcinoma is the 8th most common cancer, responsible for 462,000 new cancer cases in 2002. 2 The 5-year survival rate for esophageal carcinoma was only 14% in US 1 and 10% in Europe, 3 contributing to its position as the cancer with 3rd worse survival rate in the US 1 and as the 6th most deadly cancer throughout the world. 2 There has been a significant increase in the incidence rate of esophageal carcinoma among US males since the 1970s. 4,5 Several other countries have also noted a sharp increases in esophageal carcinoma, and in some regions, the rate has increased more than for any other malignancy. 6,7 Interestingly, the 2 main histological subtypes, squamous cell carcinoma and adenocarcinoma, differ from each other not only by the site of origin, histology, progression and risk factors, [8][9][10][11][12] but also by opposite trends in incidence over last 2 decades. 13-15 While the absolute incidence of squamous cell carcinoma of esophagus fell by one-third, the incidence of adenocarcinoma had a 6-fold increase, which represents the greatest rate of increase among all major malignancies in the US. 16 Thus, in light of increased incidence rates, late...

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“…Selective COX-2 inhibitors have a similar effect in cell cultures from endoscopic biopsies taken from BE patients [30] . Adding COX-2 inhibitors in rat diet after esophagojejunostomy had reduced progression to EAC [31,32] in some studies, while indomethacin, but not selective COX-2 inhibitors, produced a similar effect in others [33] . Several case control studies comparing EAC patients to healthy controls have shown that NSAID use can effectively prevent EAC.…”

Section: Nsaids and Eac Chemopreventionmentioning

confidence: 97%

Role of chemoprophylaxis with either NSAIDs or statins in patients with Barrett’s esophagus

Tsibouris

Vlachou

Isaacs

2014

WJGPT

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The incidence of esophageal adenocarcinoma, a poor prognosis neoplasia, has risen dramatically in recent decades. Barrett's esophagus represents the best-known risk factor for esophageal adenocarcinoma development. Non-steroidal anti-inflammatory drugs through cyclooxygenase-2 inhibition and prostaglandin metabolism regulation could control cell proliferation, increase cell apoptosis and regulate the expression of growth and angiogenic factors. Statins can achieve equivalent effects through prenylation and subsequently control of cellular signaling cascades. At present, epidemiological studies are small and underpowered. Their data could not justify either medication as a chemo-preventive agent. Population based studies have shown a 43% reduction of the odds of developing an esophageal adenocarcinoma, leaving out or stating a 25% reduction in patients consuming non-aspirin nonsteroidal antiinflammatory drugs and a 50% reduction in those patients consuming aspirin. They have also stated a 19% reduction of esophageal cancer incidence when statins have been used. Observational studies have shown that non-steroidal anti-inflammatory drugs could reduce the adenocarcinoma incidence in patients with Barrett's esophagus by 41%, while statins could reduce the risk by 43%. The cancer preventive effect has been enhanced in those patients taking a combination of non-steroidal anti-inflammatory drugs and statins (a 74% decrease). Observational data are equivocal concerning the efficacy of non-steroidal anti-inflammatory drug subclasses. Non-steroidal anti-inflammatory drugs clearly have substantial potential for toxicity, while statins are rather safe drugs. In conclusion, both non-steroidal anti-inflammatory drugs and statins are promising chemopreventive agents and deserve further exploration with interventional studies. In the meanwhile, their use is justified only in patients with cardiovascular disease.© 2014 Baishideng Publishing Group Co., Limited. All rights reserved.Key words: Esophageal adenocarcinoma; Barrett's esophagus; Non-steroidal anti-inflammatory drugs; Aspirin; Statins; Cancer chemoprevention Core tip: Esophageal adenocarcinoma remains a major burden upon health. Experimental studies have suggested that non-steroidal anti-inflammatory drugs and statins may have useful actions against esophageal cancer cells. This review of observational studies shows that non-steroidal anti-inflammatory drugs reduced adenocarcinoma incidence in patients with Barrett' s esophagus by 41%, while statins reduced the risk by 43%. The cancer preventive effect is enhanced in those patients taking a combination of non-steroidal anti-inflammatory drugs and statins (a 74% decrease). Non-steroidal anti-inflammatory drugs clearly have substantial potential for toxicity, while statins are rather safe drugs. Their combination offers promise for chemoprevention and further interventional studies are warranted.Tsibouris P, Vlachou E, Isaacs PET. Role of chemoprophylaxis REVIEWOnline Submissions: http://www.wjgnet.com/esps/

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Chemoprevention of esophageal adenocarcinoma by COX-2 inhibitors in an animal model of Barrett's esophagus

Cited by 330 publications

References 33 publications

Transcriptional profiling suggests that Barrett's metaplasia is an early intermediate stage in esophageal adenocarcinogenesis

Transcriptional profiling suggests that Barrett's metaplasia is an early intermediate stage in esophageal adenocarcinogenesis

Regular aspirin use and esophageal cancer risk

Role of chemoprophylaxis with either NSAIDs or statins in patients with Barrett’s esophagus

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