Quantification of the major urinary metabolite of PGE2 by a liquid chromatographic/mass spectrometric assay: determination of cyclooxygenase-specific PGE2 synthesis in healthy humans and those with lung cancer

Murphey, Laine J.; Williams, M. K.; Sanchez, Stephanie; Byrne, Loretta M.; Csiki, Ildiko; Oates, John A.; Johnson, David H.; Morrow, Jason D.

doi:10.1016/j.ab.2004.08.019

Cited by 160 publications

(183 citation statements)

References 18 publications

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“…Notably, the elevation in urinary PGE-M levels in OSCC patients is consistent with prior evidence of increased urinary PGE-M levels in patients with other malignancies (38,39).…”

Section: Discussionsupporting

confidence: 75%

“…Moreover, several studies have already demonstrated the promise of urinary PGE-M as a cancer risk biomarker (35)(36)(37). Increased levels of urinary PGE-M have been found in both non-small cell lung cancer and colorectal cancer patients (38,39). Finally, in a small retrospective study, we found that high levels of urinary PGE-M were associated with poor prognosis in HNSCC patients (40).…”

Section: Introductionmentioning

confidence: 66%

“…Several studies have demonstrated that traditional NSAIDs, selective COX-2 inhibitors, and aspirin suppress urinary PGE-M levels (33,38,41). In preclinical models, inhibitors of PGE 2 production have proven useful for preventing or treating a variety of tumors, including HNSCC (3,11).…”

Section: Discussionmentioning

confidence: 99%

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Elevated Levels of Urinary PGE-M Are Found in Tobacco Users and Indicate a Poor Prognosis for Oral Squamous Cell Carcinoma Patients

Kekatpure

Wang

et al. 2016

Cancer Prevention Research

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Cyclooxygenase-2 (COX-2)-derived prostaglandin E 2 (PGE 2 ) plays a role in the development and progression of epithelial malignancies. Measurements of urinary PGE-M, a stable metabolite of PGE 2 , reflect systemic PGE 2 levels. Here, we investigated whether urinary PGE-M levels were elevated in healthy tobacco users and in patients with oral squamous cell carcinoma (OSCC). Median urinary PGE-M levels were increased in healthy tobacco quid chewers [21.3 ng/mg creatinine (Cr); n ¼ 33; P ¼ 0.03] and smokers (32.1 ng/mg Cr; n ¼ 31; P < 0.001) compared with never tobacco quid chewers-never smokers (18.8 ng/mg Cr; n ¼ 30). Urinary PGE-M levels were also compared in OSCC patients versus healthy tobacco users. An approximately 1-fold increase in median urinary PGE-M level was found in OSCC patients (48.7 ng/mg Cr, n ¼ 78) versus healthy controls (24.5 ng/mg Cr, n ¼ 64; P < 0.001). We further determined whether baseline urinary PGE-M levels were prognostic in OSCC patients who underwent treatment with curative intent. A nearly 1-fold increase in baseline urinary PGE-M levels (64.7 vs. 33.8 ng/mg Cr, P < 0.001) was found in the group of OSCC patients who progressed (n ¼ 37) compared with the group that remained progression free (n ¼ 41). Patients with high baseline levels of urinary PGE-M had both worse disease-specific survival [HR, 1.01 per unit increase; 95% confidence interval (CI), 1.01-1.02; P < 0.001] and overall survival (HR, 1.01 per unit increase; 95% CI, 1.00-1.02; P ¼ 0.03). Taken together, our findings raise the possibility that NSAIDs, prototypic inhibitors of PGE 2 synthesis, may be beneficial for reducing the risk of tobacco-related aerodigestive malignancies or treating OSCC patients with high urinary PGE-M levels. Cancer Prev Res; 9(6); 428-36. Ó2016 AACR.

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“…Notably, the elevation in urinary PGE-M levels in OSCC patients is consistent with prior evidence of increased urinary PGE-M levels in patients with other malignancies (38,39).…”

Section: Discussionsupporting

confidence: 75%

Section: Introductionmentioning

confidence: 66%

See 1 more Smart Citation

Elevated Levels of Urinary PGE-M Are Found in Tobacco Users and Indicate a Poor Prognosis for Oral Squamous Cell Carcinoma Patients

Kekatpure

Wang

et al. 2016

Cancer Prevention Research

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“…Thus, EGFR inhibitors may serve a role in cancer treatment or prevention by restoring PGDH expression. Measurement of PGE 2 urinary metabolites provides a possible noninvasive and cost-effective method of monitoring therapeutic response (36).…”

Section: Discussionmentioning

confidence: 99%

Repression of Prostaglandin Dehydrogenase by Epidermal Growth Factor and Snail Increases Prostaglandin E2 and Promotes Cancer Progression

Mann¹,

Backlund

Buchanan

et al. 2006

Cancer Research

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Prostaglandin E 2 (PGE 2 ), a proinflammatory bioactive lipid, promotes cancer progression by modulating proliferation, apoptosis, and angiogenesis. PGE 2 is a downstream product of cyclooxygenase (COX) and is biochemically inactivated by prostaglandin dehydrogenase (PGDH). In the present study, we investigated the mechanisms by which PGDH is downregulated in cancer. We show that epidermal growth factor (EGF) represses PGDH expression in colorectal cancer cells. EGF receptor (EGFR) signaling induces Snail, which binds conserved E-box elements in the PGDH promoter to repress transcription. Induction of PGE 2 catabolism through inhibition of EGFR signaling blocks cancer growth in vivo. In human colon cancers, elevated Snail expression correlates well with down-regulation of PGDH. These data indicate that PGDH may serve a tumor suppressor function in colorectal cancer and provide a possible COX-2-independent way to target PGE 2 to inhibit cancer progression. (Cancer Res 2006; 66(13): 6649-56)

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“…Systemic biosynthesis of PGE 2 differs markedly between males and females in human, as in mice. 31,32 In rodents, variations in COX-2 and mPGES-1 expression at basal and pathological conditions 33,34 and different patterns of EP receptor expression 35 have been reported in females and males. Thus, sex-dependent association of PTGES polymorphisms with RA susceptibility may reflect different response to this genetic trigger in females and males owing to differences in PGE 2 metabolism.…”

Section: Discussionmentioning

confidence: 99%

Variants of gene for microsomal prostaglandin E2 synthase show association with disease and severe inflammation in rheumatoid arthritis

Korotkova¹,

Daha²,

Seddighzadeh³

et al. 2011

Eur J Hum Genet

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Quantification of the major urinary metabolite of PGE2 by a liquid chromatographic/mass spectrometric assay: determination of cyclooxygenase-specific PGE2 synthesis in healthy humans and those with lung cancer

Cited by 160 publications

References 18 publications

Elevated Levels of Urinary PGE-M Are Found in Tobacco Users and Indicate a Poor Prognosis for Oral Squamous Cell Carcinoma Patients

Elevated Levels of Urinary PGE-M Are Found in Tobacco Users and Indicate a Poor Prognosis for Oral Squamous Cell Carcinoma Patients

Repression of Prostaglandin Dehydrogenase by Epidermal Growth Factor and Snail Increases Prostaglandin E2 and Promotes Cancer Progression

Variants of gene for microsomal prostaglandin E2 synthase show association with disease and severe inflammation in rheumatoid arthritis

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