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Pharmacogenomics and Personalized Medicine

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https://read.qxmd.com/read/30697061/precision-medicine-approaches-for-the-management-of-ewing-sarcoma-current-perspectives
#1
Victoria T Rizk, Christine M Walko, Andrew S Brohl
Advancements in molecular and genetic techniques have significantly furthered our biological understanding of Ewing sarcoma (ES). ES is typified by a driving TET-ETS fusion with an otherwise relatively quiet genome. Detection of one of several characteristic fusions, most commonly EWSR1-FLI1 , is the gold standard for diagnosis. We discuss the current role of precision medicine in the diagnosis, treatment, and monitoring of ES. Continued efforts toward molecularly guided approaches are actively being pursued in ES to better refine prognosis, identify germline markers of disease susceptibility, influence therapeutic selection, effectively monitor disease activity in real time, and identify genetic and immunotherapeutic targets for therapeutic development...
2019: Pharmacogenomics and Personalized Medicine
https://read.qxmd.com/read/30679919/effects-of-coagulation-factor-vii-polymorphisms-on-warfarin-sensitivity-and-responsiveness-in-jordanian-cardiovascular-patients-during-the-initiation-and-maintenance-phases-of-warfarin-therapy
#2
Laith N Al-Eitan, Ayah Y Almasri, Sahar O Al-Habahbeh
Purpose: This study aims to investigate the relationships between genetic polymorphisms of the coagulation factor VII (FVII) gene and warfarin responsiveness and sensitivity. Patients and methods: The study population consisted of 417 subjects (207 Jordanian cardiovascular patients and 210 healthy individuals). Cardiovascular patients were classified into two groups: those sensitive to warfarin dosage (sensitive, moderate, and resistant) and those responsive to warfarin based on International Normalized Ratios (INRs; poor, good, and extensive responders)...
2019: Pharmacogenomics and Personalized Medicine
https://read.qxmd.com/read/30519074/genetic-polymorphism-of-the-methotrexate-transporter-abcg2-blood-pressure-and-markers-of-arterial-function-in-patients-with-rheumatoid-arthritis-repeated-cross-sectional-study
#3
Leena R Baghdadi, Richard J Woodman, E Michael Shanahan, Michael D Wiese, Arduino A Mangoni
Purpose: Methotrexate (MTX) treatment is associated with lower blood pressure (BP) and arterial stiffness in rheumatoid arthritis (RA). We investigated associations between single-nucleotide polymorphism (SNP) of the ATP-binding cassette efflux transporter gene ABCG2 (rs2231142), BP, and arterial stiffness in RA patients treated with MTX. Patients and methods: Clinical and 24-hour peripheral and central BP, arterial wave reflection (Augmentation Index, AIx), arterial stiffness (Pulse Wave Velocity, PWV), and intracellular MTX polyglutamate (MTXPGs) concentrations were assessed in 56 RA patients on stable treatment with MTX using a repeated cross-sectional study design with measurements at baseline and after 8 months...
2018: Pharmacogenomics and Personalized Medicine
https://read.qxmd.com/read/30510440/precision-pharmacotherapy-psychiatry-s-future-direction-in-preventing-diagnosing-and-treating-mental-disorders
#4
REVIEW
Andreas Menke
Mental disorders account for around one-third of disability worldwide and cause enormous personal and societal burden. Current pharmacotherapies and nonpharmacotherapies do help many patients, but there are still high rates of partial or no response, delayed effect, and unfavorable adverse effects. The current diagnostic taxonomy of mental disorders by the Diagnostic and Statistical Manual of Mental Disorders and the International Classification of Diseases relies on presenting signs and symptoms, but does not reflect evidence from neurobiological and behavioral systems...
2018: Pharmacogenomics and Personalized Medicine
https://read.qxmd.com/read/30464574/influence-of-msi-and-18q-loh-markers-on-capecitabine-adjuvant-monotherapy-in-colon-cancer-patients
#5
Nadica Matevska-Geshkovska, Marija Staninova-Stojovska, Aleksandra Kapedanovska-Nestorovska, Natalija Petrushevska-Angelovska, Milco Panovski, Biljana Grozdanovska, Nenad Mitreski, Aleksandar Dimovski
Purpose: The aim of this study was to evaluate whether pretreatment analysis of selected molecular markers can be used for the prediction of disease-free survival (DFS)/overall survival (OS) of capecitabine adjuvant monotherapy in colon cancer patients. Patients and methods: A total of 126 patients enrolled in a capecitabine Phase IV clinical trial were analyzed for microsatellite instability (MSI), 18q loss of heterozygosity (LOH), thymidylate synthase (TYMS) 5' variable number of tandem repeat (VNTR), and methylene tetrahydrofolate reductase (MTHFR) C677T variants...
2018: Pharmacogenomics and Personalized Medicine
https://read.qxmd.com/read/30425549/-cyp2d6-genotype-can-help-to-predict-effectiveness-and-safety-during-opioid-treatment-for-chronic-low-back-pain-results-from-a-retrospective-study-in-an-italian-cohort
#6
Concetta Dagostino, Massimo Allegri, Valerio Napolioni, Simona D'Agnelli, Elena Bignami, Antonio Mutti, Ron Hn van Schaik
Background: Opioids are widely used for chronic low back pain (CLBP); however, it is still unclear how to predict their effectiveness and safety. Codeine, tramadol and oxycodone are metabolized by CYP/CYP450 2D6 (CYP2D6), a highly polymorphic enzyme linked to allele-specific related differences in metabolic activity. Purpose: CYP2D6 genetic polymorphisms could potentially help to predict the effectiveness and safety of opioid-based drugs in clinical practice, especially in the treatment of CLBP...
2018: Pharmacogenomics and Personalized Medicine
https://read.qxmd.com/read/30410385/creating-and-validating-a-warfarin-pharmacogenetic-dosing-algorithm-for-colombian-patients
#7
Jubby Marcela Galvez, Carlos Martin Restrepo, Nora Constanza Contreras, Clara Alvarado, Carlos-Alberto Calderón-Ospina, Nidia Peña, Ricardo A Cifuentes, Daniela Duarte, Paul Laissue, Dora Janeth Fonseca
Purpose: Warfarin is an oral anticoagulant associated with adverse reaction to drugs due to wide inter- and intra-individual dosage variability. Warfarin dosage has been related to non-genetic and genetic factors. CYP2C9 and VKORC1 gene polymorphisms affect warfarin metabolism and dosage. Due to the central role of populations' ethnical and genetic origin on warfarin dosage variability, novel algorithms for Latin American subgroups are necessary to establish safe anticoagulation therapy...
2018: Pharmacogenomics and Personalized Medicine
https://read.qxmd.com/read/30310303/erratum-the-impact-of-abcb1-rs1045642-and-rs4148738-and-ces1-rs2244613-gene-polymorphisms-on-dabigatran-equilibrium-peak-concentration-in-patients-after-total-knee-arthroplasty-corrigendum
#8
(no author information available yet)
[This corrects the article on p. 127 in vol. 11, PMID: 30100750.].
2018: Pharmacogenomics and Personalized Medicine
https://read.qxmd.com/read/30288082/effects-of-abcb1-rs1045642-polymorphisms-on-the-efficacy-and-safety-of-amlodipine-therapy-in-caucasian-patients-with-stage-i-ii-hypertension
#9
Dmitry Sychev, Nadezhda Shikh, Tatiana Morozova, Elena Grishina, Kristina Ryzhikova, Elena Malova
Purpose: The aim of this study was to determine the impact of ABCB1 (MDR1) rs1045642 polymorphisms on the efficacy and safety of amlodipine in Caucasian patients. Patients and methods: The 12-week study included 100 patients. Patients with the newly diagnosed stage I-II hypertension (HT) were recruited to complete genotyping of the rs1045642 single-nucleotide polymorphism (SNP). The study design did not include a control group. Before treatment, all patients either did not undergo antihypertensive treatment at all or did not receive regular antihypertensive therapy...
2018: Pharmacogenomics and Personalized Medicine
https://read.qxmd.com/read/30271189/alk-d5f3-cdx-an-immunohistochemistry-assay-to-identify-alk-positive-nsclc-patients
#10
REVIEW
Hironori Uruga, Mari Mino-Kenudson
Screening for anaplastic lymphoma kinase ( ALK ) rearrangements is a very important process in treatment decision making for advanced non-small-cell lung cancer (NSCLC). Although fluorescent in situ hybridization (FISH) is considered the universally accepted reference standard, it is associated with technical difficulties and high costs that have made global implementation of this assay challenging. Conversely, ALK immunohistochemistry has shown high sensitivity and specificity compared to FISH and other molecular assays and is more cost-effective...
2018: Pharmacogenomics and Personalized Medicine
https://read.qxmd.com/read/30214267/qualitative-user-evaluation-of-a-revised-pharmacogenetic-educational-toolkit
#11
Rachel Mills, Susanne B Haga
Introduction: Pharmacogenetic (PGx) testing is a leading application for personalized and precision medicine; however, there are barriers, including limited provider and patient understanding, which affect its uptake. There is a need for tools that can enhance the patient and provider experience with testing and promoting the shared and informed decision-making. Materials and methods: In this study, we sought to gather additional feedback on a PGx toolkit comprised of four educational tools that had been previously evaluated through an online survey by pharmacists...
2018: Pharmacogenomics and Personalized Medicine
https://read.qxmd.com/read/30100750/the-impact-of-abcb1-rs1045642-and-rs4148738-and-ces1-rs2244613-gene-polymorphisms-on-dabigatran-equilibrium-peak-concentration-in-patients-after-total-knee-arthroplasty
#12
Dmitriy Alekseevich Sychev, Alexander Nikolaevich Levanov, Tatiana Vladimirovna Shelekhova, Pavel Olegovich Bochkov, Natalia Pavlovna Denisenko, Kristina Anatolyevna Ryzhikova, Karin Badavievich Mirzaev, Elena Anatolyevna Grishina, Mikhail Alekseevich Gavrilov, Galina Vladislavovna Ramenskaya, Aleksei Vladimirovich Kozlov, Tanya Bogoslovsky
Background: Non-vitamin K oral anticoagulants (NOACs) are commonly used for prophylaxis of venous thromboembolism (VTE) in orthopedic patients. Despite known safety and high potency of NOACs, potential interactions of NOACs with genetic polymorphisms are poorly understood. Dabigatran etexilate is one of the most commonly prescribed direct thrombin inhibitors for the prevention of VTE. The objectives of this study were to assess the effect of ABCB1 (rs1045642 and rs4148738) and CES1 (rs2244613) polymorphisms on dabigatran pharmacokinetics in patients after total knee arthroplasty...
2018: Pharmacogenomics and Personalized Medicine
https://read.qxmd.com/read/30050316/the-functional-variant-rs334558-of-gsk3b-is-associated-with-remission-in-patients-with-depressive-disorders
#13
Anastasia Levchenko, Innokentiy S Losenkov, Natalia M Vyalova, German G Simutkin, Nikolay A Bokhan, Bob Wilffert, Anton Jm Loonen, Svetlana A Ivanova
Purpose: GSK3B and AKT1 genes have been implicated in the pathogenesis of a number of psychiatric and neurological disorders. Furthermore, their genetic variants are associated with response to antidepressant pharmacotherapy. As the evidence is still incomplete and inconsistent, continuing efforts to investigate the role of these two genes in the pathogenesis and treatment of brain disorders is necessary. The aim of our study was thus to evaluate the association of variants of these two genes with depressive disorders and drug treatment response...
2018: Pharmacogenomics and Personalized Medicine
https://read.qxmd.com/read/29988737/effects-of-cyp2d6-genetic-polymorphisms-on-the-efficacy-and-safety-of-fluvoxamine-in-patients-with-depressive-disorder-and-comorbid-alcohol-use-disorder
#14
Mikhail Sergeevich Zastrozhin, Elena Anatolievna Grishina, Nataliya Petrovna Denisenko, Valentin Yurievich Skryabin, Dmitry Dmitrievich Markov, Ludmila Mikhailovna Savchenko, Evgeny Alekseevich Bryun, Dmitry Alekseevich Sychev
Background: Fluvoxamine therapy is used for treatment of patients with depressive disorder, but it is often ineffective, and some patients suffer from dose-dependent undesirable side effects such as vertigo, headache, indigestion, xerostomia, increased anxiety, etc. CYP2D6 is involved in the biotransformation of fluvoxamine. Meanwhile, the genes encoding these isoenzymes have a high level of polymorphism, which may affect the protein synthesis. Objective: The primary objective of our study was to investigate the effects of CYP2D6 genetic polymorphisms on the efficacy and safety of fluvoxamine in patients with depressive disorder and comorbid alcohol use disorder, in order to develop the algorithms of optimization of fluvoxamine therapy for reducing the risk of dose-dependent undesirable side effects and pharmacoresistance...
2018: Pharmacogenomics and Personalized Medicine
https://read.qxmd.com/read/29950882/cyp3a-and-cyp2c19-activity-in-urine-in-relation-to-cyp3a4-cyp3a5-and-cyp2c19-polymorphisms-in-russian-peptic-ulcer-patients-taking-omeprazole
#15
Natalia P Denisenko, Dmitriy A Sychev, Zhanna M Sizova, Valeriy V Smirnov, Kristina A Ryzhikova, Zhannet A Sozaeva, Elena A Grishina
Background: Proton pump inhibitors (PPIs) are metabolized by cytochrome P450. CYP2C19 is the main isoenzyme for the majority of PPI, whereas CYP3A family is a secondary enzyme for PPI biotransformation. Purpose: The aim of the study was to find if CYP3A4*22, CYP3A5*3, CYP2C19*2, CYP2C19*3 , and CYP2C19*17 genotypes are connected with CYP3A and CYP2C19 activities in Russian peptic ulcer patients taking omeprazole. Patients and methods: Forty-eight gastric or duodenal ulcer patients (15 men, 33 women; mean age 55...
2018: Pharmacogenomics and Personalized Medicine
https://read.qxmd.com/read/29922082/pharmacogenetic-association-study-on-clopidogrel-response-in-puerto-rican-hispanics-with-cardiovascular-disease-a-novel-characterization-of-a-caribbean-population
#16
Dagmar F Hernandez-Suarez, Mariana R Botton, Stuart A Scott, Matthew I Tomey, Mario J Garcia, Jose Wiley, Pedro A Villablanca, Kyle Melin, Angel Lopez-Candales, Jessicca Y Renta, Jorge Duconge
Introduction: High on-treatment platelet reactivity (HTPR) to clopidogrel imparts an increased risk for ischemic events in adults with coronary artery disease. Platelet reactivity varies with ethnicity and is influenced by both clinical and genetic variables; however, no clopidogrel pharmacogenetic studies with Puerto Rican patients have been reported. Therefore, we sought to identify clinical and genetic determinants of on-treatment platelet reactivity in a cohort of Puerto Rican patients with cardiovascular disease...
2018: Pharmacogenomics and Personalized Medicine
https://read.qxmd.com/read/29844697/emerging-biomarkers-in-the-diagnosis-of-prostate-cancer
#17
REVIEW
Xavier Filella, Esther Fernández-Galan, Rosa Fernández Bonifacio, Laura Foj
Prostate cancer (PCa) is the second most common cancer in men worldwide. A large proportion of PCa are latent, never destined to progress or affect the patients' life. It is of utmost importance to identify which PCa are destined to progress and which would benefit from an early radical treatment. Prostate-specific antigen (PSA) remains the most used test to detect PCa. Its limited specificity and an elevated rate of overdiagnosis are the main problems associated with PSA testing. New PCa biomarkers have been proposed to improve the accuracy of PSA in the management of early PCa...
2018: Pharmacogenomics and Personalized Medicine
https://read.qxmd.com/read/29731659/meta-analysis-of-the-association-of-the-haptoglobin-genotype-with-cardiovascular-outcomes-and-the-pharmacogenomic-interactions-with-vitamin-e-supplementation
#18
Rabea Asleh, Alexandros Briasoulis, Elliot M Berinstein, Joshua B Wiener, Mohan Palla, Sudhir S Kushwaha, Andrew P Levy
Objectives: The objectives of the study were to compile and summarize the data from all of the clinical trials designed to examine the association between haptoglobin (Hp) genotype and incidence of cardiovascular (CV) events in patients with diabetes mellitus (DM) and to assess the impact of vitamin E treatment on CV outcomes according to the Hp genotype. Background: The Hp genotype could serve as a predictive biomarker to DM patients who may benefit from vitamin E therapy...
2018: Pharmacogenomics and Personalized Medicine
https://read.qxmd.com/read/29731658/budget-impact-model-for-oncopharmacogenetics-from-the-perspective-of-mandatory-basic-health-insurance-in-switzerland-using-the-example-of-breast-cancer
#19
Thomas D Szucs, Kevin P Szillat, Eva Blozik
Single-nucleotide polymorphisms (SNPs) can severely impact individual drug response and health outcomes in cancer patients. Genetic tests to screen for marker SNPs are available to adjust the drug dose of oncologicals to the patient's needs. However, it is unclear whether the positive effects outbalance the increased costs or even lead to an overall cost reduction. This very pragmatic analysis used three frequently used oncologicals for the treatment of breast cancer to evaluate whether preemptive pharmacogenetic testing may have a cost-reducing impact on health care spending in the Swiss health care system...
2018: Pharmacogenomics and Personalized Medicine
https://read.qxmd.com/read/29692621/h3africa-current-perspectives
#20
REVIEW
Nicola Mulder, Alash'le Abimiku, Sally N Adebamowo, Jantina de Vries, Alice Matimba, Paul Olowoyo, Michele Ramsay, Michelle Skelton, Dan J Stein
Precision medicine is being enabled in high-income countries by the growing availability of health data, increasing knowledge of the genetic determinants of disease and variation in response to treatment (pharmacogenomics), and the decreasing costs of data generation, which promote routine application of genomic technologies in the health sector. However, there is uncertainty about the feasibility of applying precision medicine approaches in low- and middle-income countries, due to the lack of population-specific knowledge, skills, and resources...
2018: Pharmacogenomics and Personalized Medicine
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