Indomethacin but not a selective cyclooxygenase-2 inhibitor inhibits esophageal adenocarcinogenesis in rats

Esquivias, Paula; Morandeira, Antonio; Escartín, Alfredo; Cebrián, Carmelo; Santander, Sonia; Esteva, Francisco J.; García-González, María Asunción; Ortego, Javier; Lanas, Ángel; Piazuelo, Elena

doi:10.3748/wjg.v18.i35.4866

Cited by 7 publications

(5 citation statements)

References 26 publications

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“…[31] Supporting this hypothesis, animal models of reflux suggest that anti-inflammatory medications can both decrease the risk of esophagitis resulting from reflux-induced damage and the risk of Barrett’s-like changes. [32,33] The mechanisms of action for aspirin and other NSAIDS are different, however, and our results and those of other recent studies suggest that they may have different effects on prevention of BE. [8,16] The exact biologic mechanism of chemoprevention for each agent is not known, though it may be related to differing inhibition of cyclooxygenase 1 vs. cyclooxygenase 2, or differences in modification of other pathways that modify cell growth, apoptosis or angiogenesis;[34,35] such differences have resulted in biologic differences between these classes of agents for other conditions, such as cardiovascular disease.…”

Section: Discussionmentioning

confidence: 51%

Aspirin and Nonsteroidal Anti-Inflammatory Drug Use and the Risk of Barrett’s Esophagus

2014

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Background The use of aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) may decrease the risk of esophageal adenocarcinoma; however, it is unknown where these agents may act in the proposed pathway from normal mucosa to Barrett’s esophagus to esophageal adenocarcinoma. Aim To evaluate the association between aspirin and NSAID use and Barrett’s esophagus in a case-control study within a large community-based population. Methods We conducted a case-control study of aspirin/NSAID use and Barrett’s esophagus within the Kaiser Permanente Northern California population. Cases had a new diagnosis of Barrett’s esophagus between October 2002 and September 2005; controls were members without a diagnosis of Barrett’s esophagus. Aspirin/NSAID “users” were persons with at least weekly use of either aspirin or NSAIDs in the year prior to the index date. Results Persons with Barrett’s esophagus were less likely to use aspirin than population controls (odds ratio [OR]=0.59, 95% confidence interval [CI] 0.39–0.87); a stronger association was found among cases and controls with reflux symptoms (OR=0.49, 95% CI 0.32–0.75; p-value interaction=0.004). Similar associations were found with use of either aspirin and/or non-aspirin NSAIDs) (OR= 0.53, 95% CI 0.35–0.81), although NSAID use alone was not significantly associated with Barrett’s esophagus (OR=0.74, 95% CI 0.47–1.16). The strength of the association was highest among persons with at least moderate to high total medication intake. Conclusions Regular use of aspirin or NSAIDs was associated with a decreased risk of Barrett’s esophagus, particularly among persons with GERD symptoms. These findings have implications for chemoprevention, as some of the previously described protective association between aspirin/NSAIDs and esophageal adenocarcinoma may be explained by events that occur prior to the development of Barrett’s esophagus.

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Section: Discussionmentioning

confidence: 51%

Aspirin and Nonsteroidal Anti-Inflammatory Drug Use and the Risk of Barrett’s Esophagus

2014

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“…Interestingly, a possible involvement of COX-1 in the disease pathophysiology had already been suggested by the co-expression of both COX isoforms and angiogenic (VEGF-A) and lymphangiogenic (VEGF-C) growth factors in primary human tumor samples [62]. More recently, a possible cooperation of COX-1 and COX-2 isoforms has been suggested in an investigation of the PGE 2 pathway in a rat model of esophageal adenocarcinoma induced by gastroduodenal reflux resulting from esophagojejunostomy [63], as well as by the finding that in the same experimental model indomethacin (a dual COX-1/COX-2 inhibitor) reduced the inflammatory lesions and tumor development, whereas a selective COX-2 inhibitor (MF-tricyclic) was ineffective [64]. Interestingly, a recent meta-analysis of nine observational studies has shown that both low-dose aspirin and non-aspirin COX inhibitor use is associated with a reduced risk of developing esophageal adenocarcinoma in patients with Barrett’s esophagus [65].…”

Section: Cox-1 Involvement In Neoplastic Diseasesmentioning

confidence: 99%

Cyclooxygenase-1 (COX-1) and COX-1 Inhibitors in Cancer: A Review of Oncology and Medicinal Chemistry Literature

2018

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Prostaglandins and thromboxane are lipid signaling molecules deriving from arachidonic acid by the action of the cyclooxygenase isoenzymes COX-1 and COX-2. The role of cyclooxygenases (particularly COX-2) and prostaglandins (particularly PGE2) in cancer-related inflammation has been extensively investigated. In contrast, COX-1 has received less attention, although its expression increases in several human cancers and a pathogenetic role emerges from experimental models. COX-1 and COX-2 isoforms seem to operate in a coordinate manner in cancer pathophysiology, especially in the tumorigenesis process. However, in some cases, exemplified by the serous ovarian carcinoma, COX-1 plays a pivotal role, suggesting that other histopathological and molecular subtypes of cancer disease could share this feature. Importantly, the analysis of functional implications of COX-1-signaling, as well as of pharmacological action of COX-1-selective inhibitors, should not be restricted to the COX pathway and to the effects of prostaglandins already known for their ability of affecting the tumor phenotype. A knowledge-based choice of the most appropriate tumor cell models, and a major effort in investigating the COX-1 issue in the more general context of arachidonic acid metabolic network by using the systems biology approaches, should be strongly encouraged.

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“…Regarding the COX pathway, COX2, prostaglandin E synthase, prostaglandin receptors E 2 and E 4 overexpression and PGE 2 overproduction have been observed during rat esophageal adenocarcinogenesis (20,21), mimicking the expression profiles of these markers in both human Barrett's and esophageal adenocarcinoma (22,23). Administration of different COX inhibitors has been shown to provoke a significant reduction in PGE 2 production as well as to prevent the development of adenocarcinoma in this experimental model (24)(25)(26)(27).…”

Section: Discussionmentioning

confidence: 66%

Effect of aspirin treatment on the prevention of esophageal adenocarcinoma in a rat experimental model

et al. 2014

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Abstract. Aspirin has been proposed in recent years as a candidate for chemoprevention of adenocarcinoma in patients with Barrett's esophagus. The aim of the present study was to evaluate the effect of acetylsalicylic acid (ASA) in an experimental model of esophageal adenocarcinoma. An animal model of gastroenteroesophageal reflux was established using Wistar rats undergoing esophagojejunostomy with gastric preservation. Following surgery, rats were divided into three groups: i) control (vehicle); ii) ASA 50 mg/kg/day; and iii) ASA 5 mg/kg/day. Four months after surgery, the surviving animals were sacrificed and the rat esophagi were assessed for histological and biochemical [prostaglandin E 2 (PGE 2 ) and lipoxin A 4 (LXA 4 ) levels] analysis. As in the control rats, those receiving aspirin treatment showed no decrease in inflammation grade, extent of ulcerated esophageal mucosa, length of intestinal metaplasia in continuity with anastomosis, presence of intestinal metaplasia beyond anastomosis, severity of dysplasia or incidence of adenocarcinoma. In contrast, aspirin-treated rats showed decreased esophageal tissue levels of PGE 2 and increased LXA 4 , significantly in the high-dose aspirin group (P=0.008 and P=0.01, respectively). In this rat model of gastroesophageal reflux, the administration of aspirin modified esophageal tissue levels of PGE 2 and LXA 4 , but was not effective in preventing the development of esophageal adenocarcinoma.

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Indomethacin but not a selective cyclooxygenase-2 inhibitor inhibits esophageal adenocarcinogenesis in rats

Abstract: In this rat model of gastrointestinal reflux, indomethacin was associated with a decrease in the severity of esophagitis and reduced development of esophageal intestinal metaplasia and adenocarcinoma.

Cited by 7 publications

References 26 publications

Aspirin and Nonsteroidal Anti-Inflammatory Drug Use and the Risk of Barrett’s Esophagus

Aspirin and Nonsteroidal Anti-Inflammatory Drug Use and the Risk of Barrett’s Esophagus

Cyclooxygenase-1 (COX-1) and COX-1 Inhibitors in Cancer: A Review of Oncology and Medicinal Chemistry Literature

Effect of aspirin treatment on the prevention of esophageal adenocarcinoma in a rat experimental model

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