Preparation of the Major Urinary Metabolite of (-)-Prostaglandin E(2).
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ABSTRACT:
SUBMITTER: Taber DF
PROVIDER: S-EPMC2719863 | biostudies-literature | 2009 Aug
REPOSITORIES: biostudies-literature
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Preparation of the Major Urinary Metabolite of (-)-Prostaglandin E(2).
Taber Douglass F DF Gu Peiming P
Tetrahedron 20090801 31
The best way to measure whole body production of the locally acting hormone prostaglandin E(2) (PGE(2)) is to assess the accumulation of the major urinary metabolite, PGE(2) U (M). A practical preparation of this delicate diacid is described. This synthetic PGE(2)U(M) will enable production of the antibodies that will be used to quantify this key metabolite. ...[more]
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Project description:ObjectivesCyclooxygenase-2-derived prostaglandin E2 (PGE2) is highly involved in the promotion of cancer progression. The end product of this pathway, PGE-major urinary metabolite (PGE-MUM), is a stable metabolite of PGE2 that can be assessed non-invasively and repeatedly in urine samples. The aim of this study was to assess the dynamic changes in perioperative PGE-MUM levels and their prognostic significance in non-small-cell lung cancer (NSCLC).MethodsBetween December 2012 and March 2017, 211 patients who underwent complete resection for NSCLC were analysed prospectively. PGE-MUM levels in 2 spot urine samples taken 1 or 2 days preoperatively and 3-6 weeks postoperatively were measured using a radioimmunoassay kit.ResultsElevated preoperative PGE-MUM levels were associated with tumour size, pleural invasion and advanced stage. Multivariable analysis revealed that age, pleural invasion, lymph node metastasis and postoperative PGE-MUM levels were independent prognostic factors. In matched pre- and postoperative urine samples obtained from patients who are eligible for adjuvant chemotherapy, an increase in PGE-MUM levels following resection was an independent prognostic factor (hazard ratio 3.017, P = 0.005). Adjuvant chemotherapy improved survival in patients with increased PGE-MUM levels after resection (5-year overall survival, 79.0 vs 50.4%, P = 0.027), whereas survival benefit was not observed in those with decreased PGE-MUM levels (5-year overall survival, 82.1 vs 82.3%, P = 0.442).ConclusionsIncreased preoperative PGE-MUM levels can reflect tumour progression and postoperative PGE-MUM levels are a promising biomarker for survival after complete resection in patients with NSCLC. Perioperative changes in PGE-MUM levels may aid in determining the optimal eligibility for adjuvant chemotherapy.
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Project description:Background and aimUlcerative colitis (UC) is usually detected by clinical symptoms, such as bleeding and diarrhea; however, it is rather difficult to assess during asymptomatic clinical remission (CR). Hence, there is a need for a biomarker that can reliably detect UC during remission. We previously reported on the utility of the prostaglandin E-major urinary metabolite (PGE-MUM) as a biomarker reflecting UC activity. In this study, we evaluated the effectiveness of the PGE-MUM in the diagnosis of endoscopic, histological, and histo-endoscopic mucosal remission of UC, comparing with fecal tests.MethodsThis prospective study was conducted at the Jikei University Hospital between August 2017 and January 2021. Patients with UC in CR scheduled to undergo colonoscopy were included. The association between the PGE-MUM with endoscopic remission (ER), histological remission (HR), and complete mucosal healing (CMH, defined as histo-endoscopic remission) was analyzed. We also compared the area under the curve (AUC) for the receiver operating characteristic curves between PGE-MUM, fecal calprotectin (FC), and fecal immunochemical test (FIT).ResultsIn total, 128 patients were analyzed. PGE-MUM differed significantly in ER versus non-ER (14.5 vs 16.7, P = 0.028), HR versus non-HR (14.2 vs 17.4, P = 0.004), and CMH versus non-CMH (14.3 vs 16.7, P = 0.021). There were no significant differences between the AUCs for PGE-MUM, FC, and FIT for ER, HR, or CMH.ConclusionsThe PGE-MUM can determine CMH in UC even during CR, regardless of the disease phenotype, indicating its clinical benefit for non-invasive monitoring.
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Project description:BackgroundTo evaluate the reduced-risk potential of alternative tobacco products, biomarkers that are involved in the biological pathways affected by cigarette smoking and smoking cessation are needed. Isoprostanes, a measure of oxidative stress, appear to be influenced by smoking and reversible upon smoking cessation and therefore could be a good biomarker. This review aims at quantifying the effect of smoking and smoking cessation on levels of urinary 8-iso prostaglandin F2? (8-epi-PGF2?), an isoprostane.MethodsPubMed and Scopus databases were searched for publications that reported 8-epi-PGF2? levels in smokers and nonsmokers as well as articles reporting the effect of smoking cessation on 8-epi-PGF2? levels.ResultsEighteen studies assessing 8-epi-PGF2? levels by smoking status were identified. Five of the papers reported the results as quantity excreted in 24-hour urine (?g/24?h), and 15 reported creatinine adjusted values. The meta-analyses show increased levels of 8-epi-PGF2? in current smokers compared with nonsmokers (mean difference?=?0.16, 95% confidence interval [95%CI]: 0.14-0.19??g/24?h with inconsistency statistic [I2]?=?98%; mean difference?=?172.38, 95%CI: 152.75-192.01?pg/mg creatinine with I2?=?89%, respectively). There were too few publications to perform a meta-analysis assessing the effects of smoking cessation on 8-epi-PGF2? levels.ConclusionsDue to the high heterogeneity among the studies included in these meta-analyses, it is difficult to generalize the results; however, our study indicates increased levels of 8-epi-PGF2? and therefore increased oxidative stress in smokers compared with nonsmokers. More studies are still needed to assess if 8-epi-PGF2? levels are reversible after cessation.
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