Characterization of the Prostaglandin E2 Pathway in a Rat Model of Esophageal Adenocarcinoma

Piazuelo, Elena; Santander, Sonia; Cebrián, Carmelo; Jiménez, Pilar; Pastor, C.; García-González, María Asunción; Esteva, Francisco J.; Esquivias, Paula; Ortego, Javier; Lanas, Fernando

doi:10.2174/156800912799095199

Cited by 6 publications

(5 citation statements)

References 25 publications

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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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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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“…What’s more, overexpression of EP 2 exhibited significant correlation with worse 5-year OS than those with negative result (10.9% vs. 34.1%, P<0.001) ( 8 ). Piazuelo et al found EP 2 may play important roles in the development of esophageal adenocarcinoma (EAC) induced by gastroduodenal reflux in the rat ( 9 ). In Barrett’s esophagus adenocarcinoma and EAC, they also found the EP 2 was overexpressed, and they thought it might be used as a new method to treat Barrett's esophagus in the future ( 10 ).…”

Section: Discussionmentioning

confidence: 99%

The role of prostaglandin E receptor 2 and epidermal growth factor receptor in esophageal squamous cell carcinoma patients with (pN+) regional lymph node metastasis

Luo¹,

He²,

Yan³

et al. 2019

Transl. Cancer Res.

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Background To find the relationship between prostaglandin E receptor 2 (EP 2 ) and epidermal growth factor receptor (EGFR) in esophageal squamous cell carcinoma (ESCC) patients with regional lymph nodes metastasis (pN+) who had undergone curative resection, and to analyze them in the role of judging prognosis. Methods Sixty-three patients with ESCC who underwent attempted curative esophagectomy with lymph node metastasis were collected. Immunohistochemistry (IHC) was used to analyse the expression of EP 2 and EGFR in tumor tissues. We analyzed the relationship between the two markers. Furthermore, we analyzed the role of EP 2 and EGFR in disease-free survival (DFS) and overall survival (OS). Results The expression rate of EP 2 and EGFR in this study were 73.0%, 85.7%, respectively. And the EP 2 status was closely related with the expression of EGFR in tumor tissues (χ 2 =0.260, P=0.011). The patients with EP 2 or EGFR positive expression had a shorter DFS and OS than the negative group. Further analysis found EGFR is an important prognostic factor for DFS and OS (P<0.001), the expression of EP 2 was related with PFS (P=0.048), but it was not an independent influencing factors for OS (P>0.05). Conclusions The expression of EP 2 and EGFR were high in tumor tissues of (pN+) ESCC, and they are playing a key role in the prognosis of ESCC patients with local lymph node metastases.

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“…The surgical model of Barrett's esophagus and esophageal adenocarcinoma in the rat appears to be a suitable model of human disease (12). 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: 99%

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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Characterization of the Prostaglandin E2 Pathway in a Rat Model of Esophageal Adenocarcinoma

Cited by 6 publications

References 25 publications

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

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

The role of prostaglandin E receptor 2 and epidermal growth factor receptor in esophageal squamous cell carcinoma patients with (pN+) regional lymph node metastasis

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

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