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      OPRM1 c.118A>G Polymorphism and Duration of Morphine Treatment Associated with Morphine Doses and Quality-of-Life in Palliative Cancer Pain Settings

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          Abstract

          Despite increased attention on assessment and management, pain remains the most persistent symptom in patients with cancer, in particular in end-of-life settings, with detrimental impact on their quality-of-life (QOL). We conducted this study to evaluate the added value of determining some genetic and non-genetic factors to optimize cancer pain treatment. Eighty-nine patients were included in the study for the evaluation of palliative cancer pain management. The regression analysis showed that age, OPRM1 single nucleotide polymorphism (SNP), as well as the duration of morphine treatment were significantly associated with morphine doses at 24 h (given by infusion pump; p = 0.043, 0.029, and <0.001, respectively). The mean doses of morphine decreased with age but increased with the duration of morphine treatment. In addition, patients with AG genotype c.118A>G OPRM1 needed a higher dose of morphine than AA patients. Moreover, metastases, OPRM1 SNP, age, and gender were significantly associated with the QOL in our population. In particular, AA patients for OPRM1 SNP had significantly lower cognitive function than AG patients, a result not previously reported in the literature. These findings could help increase the effectiveness of morphine treatment and enhance the QOL of patients in regards to personalized medicine.

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          Most cited references 62

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          Use of opioid analgesics in the treatment of cancer pain: evidence-based recommendations from the EAPC.

          Here we provide the updated version of the guidelines of the European Association for Palliative Care (EAPC) on the use of opioids for the treatment of cancer pain. The update was undertaken by the European Palliative Care Research Collaborative. Previous EAPC guidelines were reviewed and compared with other currently available guidelines, and consensus recommendations were created by formal international expert panel. The content of the guidelines was defined according to several topics, each of which was assigned to collaborators who developed systematic literature reviews with a common methodology. The recommendations were developed by a writing committee that combined the evidence derived from the systematic reviews with the panellists' evaluations in a co-authored process, and were endorsed by the EAPC Board of Directors. The guidelines are presented as a list of 16 evidence-based recommendations developed according to the Grading of Recommendations Assessment, Development and Evaluation system. Copyright © 2012 Elsevier Ltd. All rights reserved.
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            Kinetics of human soluble and membrane-bound catechol O-methyltransferase: a revised mechanism and description of the thermolabile variant of the enzyme.

            Human soluble (S) and membrane-bound (MB) catechol O-methyltransferase (COMT, EC 2.1.1.6) enzymes have been expressed at sufficiently high levels in Escherichia coli and in baculovirus-infected insect cells to allow kinetic characterization of the enzyme forms. The use of tight-binding inhibitors such as entacapone enabled the estimation of actual enzyme concentrations and, thereby, comparison of velocity parameters, substrate selectivity, and regioselectivity of the methylation of both enzyme forms. Kinetics of the methylation reaction of dopamine, (-)-noradrenaline, L-dopa, and 3,4-dihydroxybenzoic acid was studied in detail. Here, the catalytic number (Vmax) of S-COMT was somewhat higher than that of MB-COMT for all four substrates. The Km values varied considerably, depending on both substrate and enzyme form. S-COMT showed about 15 times higher Km values for catecholamines than MB-COMT. The distinctive difference between the enzyme forms was also the higher affinity of MB-COMT for the coenzyme S-adenosyl-L-methionine (AdoMet). The average dissociation constants Ks were 3.4 and 20.2 microM for MB-COMT and S-COMT, respectively. Comparison between the kinetic results and the atomic structure of S-COMT is presented, and a revised mechanism for the reaction cycle is discussed. Two recently published human COMT cDNA sequences differed in the position of S-COMT amino acid 108, the residue being either Val-108 [Lundström et al. (1991) DNA Cell. Biol. 10, 181-189] or Met-108 [Bertocci et al. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 1416-1420].(ABSTRACT TRUNCATED AT 250 WORDS)
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              Applied Multivariate Statistics For The Social Sciences

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                Author and article information

                Contributors
                Role: Academic Editor
                Role: Academic Editor
                Role: Academic Editor
                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                27 March 2017
                April 2017
                : 18
                : 4
                Affiliations
                [1 ]Laboratory of Pharmacology, Clinical Pharmacy and Quality Control of Drugs, Pôle Technologie- Santé (PTS), Faculty of Pharmacy, Saint-Joseph University, Beirut 1107 2180, Lebanon; lucine.halepian@ 123456hotmail.com (L.H.); lydia.khabbaz@ 123456usj.edu.lb (L.R.K.)
                [2 ]Department of Public Health, Faculty of Medicine, Saint-Joseph University, Beirut 1107 2180, Lebanon; pronada99@ 123456hotmail.com
                [3 ]Department of Prosthodontics, Faculty of Dental Medicine, Saint-Joseph University, Beirut 1107 2180, Lebanon
                [4 ]University of Auvergne, CROC-EA4847, Centre de Recherche en Odontologie Clinique, BP 10448, Clermont-Ferrand F-63000, France
                [5 ]Department of Hemato-Oncology, Hôtel-Dieu de France Hospital, Faculty of Medicine, Saint-Joseph University, Beirut 1107 2180, Lebanon; chahine_georges@ 123456hotmail.com (G.C.); joseph.kattan@ 123456usj.edu.lb (J.K.)
                Author notes
                [* ]Correspondence: aline.hajj@ 123456usj.edu.lb ; Tel.: +961-3-873-621; Fax: +961-1-421-022
                [†]

                These authors contributed equally to this work.

                Article
                ijms-18-00669
                10.3390/ijms18040669
                5412267
                28346387
                © 2017 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                Categories
                Article

                Molecular biology

                morphine, polymorphism, oprm1, abcb1, comt, pain, pharmacogenetics, cancer, quality-of-life

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