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Pharmacogenomics

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https://www.readbyqxmd.com/read/28546997/pharmacogenomic-findings-from-clinical-whole-exome-sequencing-of-diagnostic-odyssey-patients
#1
Margot A Cousin, Eric T Matey, Patrick R Blackburn, Nicole J Boczek, Tammy M McAllister, Teresa M Kruisselbrink, Dusica Babovic-Vuksanovic, Konstantinos N Lazaridis, Eric W Klee
BACKGROUND: We characterized the pharmacogenomics (PGx) results received by diagnostic odyssey patients as secondary findings during clinical whole exome sequencing (WES) testing as a part of their care in Mayo Clinic's Individualized Medicine Clinic to determine the potential benefits and limitations to this cohort. METHODS: WES results on 94 patients included a subset of PGx variants in CYP2C19,CYP2C9, and VKORC1 if identified in the patient. Demographic, phenotypic, and medication usage information was abstracted from patient medical data...
May 2017: Molecular Genetics & Genomic Medicine
https://www.readbyqxmd.com/read/28545225/state-of-art-of-cancer-pharmacogenomics-in-latin-american-populations
#2
REVIEW
Andrés López-Cortés, Santiago Guerrero, María Ana Redal, Angel Tito Alvarado, Luis Abel Quiñones
Over the past decades, several studies have shown that tumor-related somatic and germline alterations predicts tumor prognosis, drug response and toxicity. Latin American populations present a vast geno-phenotypic diversity due to the great interethnic and interracial mixing. This genetic flow leads to the appearance of complex characteristics that allow individuals to adapt to endemic environments, such as high altitude or extreme tropical weather. These genetic changes, most of them subtle and unexplored, could establish a mutational profile to develop new pharmacogenomic therapies specific for Latin American populations...
May 23, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28534527/role-of-the-ugt2b17-deletion-in-exemestane-pharmacogenetics
#3
S Luo, G Chen, C Truica, C C Baird, K Leitzel, P Lazarus
Exemestane (EXE) is an aromatase inhibitor used for the prevention and treatment of breast cancer. The major metabolic pathway for EXE is reduction to form the active 17β-dihydro-EXE (17β-DHE) and subsequent glucuronidation to 17β-hydroxy-EXE-17-O-β-D-glucuronide (17β-DHE-Gluc) by UGT2B17. The aim of the present study was to determine the effects of UGT2B17 copy number variation on the levels of urinary and plasma 17β-DHE-Gluc and 17β-DHE in patients taking EXE. Ninety-six post-menopausal Caucasian breast cancer patients with ER+ breast tumors taking 25 mg EXE daily were recruited into this study...
May 23, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28534526/impact-of-genetic-polymorphisms-determining-leukocyte-neutrophil-count-on-chemotherapy-toxicity
#4
S J Glisovic, Y D Pastore, V Gagne, M Plesa, C Laverdière, J M Leclerc, D Sinnett, M Krajinovic
Neutropenia and infection are major dose-limiting side effects of chemotherapy. The risk of initial infection and subsequent complications are directly related to the depth and duration of neutropenia. Recent genome-wide association studies identified variants in DARC and CXCL2 genes, and in ORMDL3-GSDMA-CSF3 locus on chromosome 17q21 that influence white blood cell and neutrophil counts in healthy individuals. To investigate whether polymorphisms in these loci in conjunction with chemotherapy may modulate risk of treatment complications, we analyzed 21 SNPs across these genes for an association with chemotherapy-related neutropenia and infection in 286 Caucasian children with acute lymphoblastic leukemia...
May 23, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28526450/the-association-of-single-nucleotide-polymorphisms-in-the-oxytocin-receptor-and-g-protein-coupled-receptor-kinase-6-grk6-genes-with-oxytocin-dosing-requirements-and-labor-outcomes
#5
Chad A Grotegut, Emily Ngan, Melanie E Garrett, Marie Lynn Miranda, Allison E Ashley-Koch, Geeta K Swamy
BACKGROUND: Oxytocin is a potent uterotonic agent that is widely used for induction and augmentation of labor. Oxytocin has a narrow therapeutic index and the optimal dosing for any individual woman varies widely. OBJECTIVE: The objective of this study was to determine if genetic variation in the oxytocin receptor (OXTR) or in the gene encoding G protein-coupled receptor kinase 6 (GRK6), which regulates desensitization of the OXTR, could explain variation in oxytocin dosing and labor outcomes among women being induced near term...
May 16, 2017: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28526150/pharmacogenomics-in-pain-management
#6
REVIEW
Ramsey Saba, Alan D Kaye, Richard D Urman
There is interpatient variability to analgesic administration. Much can be traced to pharmacogenomics variations between individuals. Certain ethnicities are more prone to reduced function of CYP2D6. Weak opioids are subject to interpatient variation based on their CYP2D6 type. Strong opioids have variations based on their transport and individual metabolism. Several cytochrome enzymes have been found to be involved with ketamine but there is no strong evidence of individual polymorphisms manifesting in clinical outcomes...
June 2017: Anesthesiology Clinics
https://www.readbyqxmd.com/read/28526149/pharmacogenomics-in-anesthesia
#7
REVIEW
Ramsey Saba, Alan D Kaye, Richard D Urman
A significant number of commonly administered medications in anesthesia show wide clinical interpatient variability. Some of these include neuromuscular blockers, opioids, local anesthetics, and inhalation anesthetics. Individual genetic makeup may account for and predict cardiovascular outcomes after cardiac surgery. These interactions can manifest at any point in the perioperative period and may also only affect a specific system. A better understanding of pharmacogenomics will allow for more individually tailored anesthetics and may ultimately lead to better outcomes, decreased hospital stays, and improved patient satisfaction...
June 2017: Anesthesiology Clinics
https://www.readbyqxmd.com/read/28525818/hypertension-update-jnc8-and-beyond
#8
REVIEW
Tara Shrout, David W Rudy, Michael T Piascik
Hypertension is the most preventable major risk factor for cardiovascular morbidity and mortality. The etiology of elevated blood pressure is a complex process involving the interaction of genetics, demographics, comorbid disorders, and environmental influences. Effective hypertensive therapy has been shown to reduce cardiovascular morbidity and mortality. JNC reports have served as a valuable source of guidelines, and JNC 8 is the most recently updated guideline for the prevention, diagnosis, and treatment of hypertension...
May 16, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28523515/distribution-of-exogenous-and-endogenous-cyp3a-markers-and-related-factors-in-healthy-males-and-females
#9
Jieon Lee, Andrew HyoungJin Kim, SoJeong Yi, SeungHwan Lee, Seo Hyun Yoon, Kyung-Sang Yu, In-Jin Jang, Joo-Youn Cho
Cytochrome P450 (CYP) 3A is an important drug-metabolizing enzyme in humans. Assessing CYP3A activity is necessary for predicting therapeutic outcomes or the potential adverse events of various therapeutics. This study sought to evaluate the distribution of endogenous and exogenous markers reflecting hepatic CYP3A activity and related factors affecting its activity in healthy male and female. Each subject was given a single 1 mg dose of midazolam intravenously. Pharmacokinetics, pharmacometabolomics, and pharmacogenomics analyses were performed to evaluate CYP3A activity...
May 18, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28515818/pharmacogenomic-testing-for-psychotropic-medication-selection-a-systematic-review-of-the-assurex-genesight-psychotropic-test
#10
(no author information available yet)
BACKGROUND: A large proportion of the Ontario population lives with a diagnosed mental illness. Nearly 5% of Ontarians have major depressive disorder, and another 5% have another type of depressive disorder, bipolar disorder, schizophrenia, anxiety, or some other disorder not otherwise specified. Medications are commonly used to treat mental illness, but choosing the right medication for each patient is challenging, and more than 40% of patients discontinue their medication within 90 days because of adverse effects or lack of response...
2017: Ontario Health Technology Assessment Series
https://www.readbyqxmd.com/read/28514737/integration-of-phytochemicals-and-phytotherapy-into-cancer-precision-medicine
#11
REVIEW
Thomas Efferth, Mohamed E M Saeed, Elhaj Mirghani, Awadh Alim, Zahir Yassin, Elfatih Saeed, Hassan E Khalid, Salah Daak
Concepts of individualized therapy in the 1970s and 1980s attempted to develop predictive in vitro tests for individual drug responsiveness without reaching clinical routine. Precision medicine attempts to device novel individual cancer therapy strategies. Using bioinformatics, relevant knowledge is extracted from huge data amounts. However, tumor heterogeneity challenges chemotherapy due to genetically and phenotypically different cell subpopulations, which may lead to refractory tumors. Natural products always served as vital resources for cancer therapy (e...
April 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28514126/-haptoglobin-polymorphism-as-an-independent-predictor-of-diabetic-nephropathy-and-retinopathy
#12
Inbal Dahan, Nadia Thauho, Farid Nakhoul, Nakhoul Nakhoul, Hanin Jabaly, Evgeny Farber
The antioxidant protein haptoglobin (Hp) plays a major role in the development of diabetic complications such as diabetic nephropathy and retinopathy. In humans, two alleles of Hp were identified: 1 and 2 with three possible genotypes: 1-1, 2-1, and 2-2. The Hp protein products differ in their biochemical and biophysical properties, such as their antioxidant capacity. The Hp1 protein is superior to the Hp2 protein in binding to free hemoglobin and neutralizing its oxidative potential and the accompanying renal and retinal injury...
July 2016: Harefuah
https://www.readbyqxmd.com/read/28508787/the-importance-of-gene-drug-drug-interactions-in-pharmacogenomics-decision-support-an-analysis-based-on-austrian-claims-data
#13
Kathrin Blagec, Wolfgang Kuch, Matthias Samwald
While pharmacogenomic testing combined with clinical decision support has the potential to increase the safety and efficacy of medical treatments, the intake of multiple prescription drugs can - if not sufficiently addressed by decision support solutions - impair the effectiveness of such interventions by modulating the capacity of precisely those enzymes whose function pharmacogenomic tests try to predict. We quantified the potential extent of such drug-mediated mismatches between genotype-derived phenotypes and real phenotypes, commonly called "phenoconversion", by screening claims data from 1,587,829 Austrian health insurance holders of the years 2006 and 2007 for concomitant prescriptions of drugs that can be dosed based on pharmacogenomics, and drugs that modulate enzyme activity...
2017: Studies in Health Technology and Informatics
https://www.readbyqxmd.com/read/28508778/supporting-molecular-tumor-boards-in-molecular-guided-decision-making-the-current-status-of-five-german-university-hospitals
#14
Marc Hinderer, Melanie Boerries, Florian Haller, Sebastian Wagner, Stefanie Sollfrank, Till Acker, Hans-Ulrich Prokosch, Jan Christoph
BACKGROUND: German university hospitals have started to establish molecular tumor boards in order to enable physicians to make molecular-guided decisions. OBJECTIVE: Our aim was to describe the organizational structure and procedures which are currently supporting the molecular tumor boards of five German university hospitals. METHODS: We conducted semi-structured interviews with experts of five university hospitals between December 2016 and February 2017...
2017: Studies in Health Technology and Informatics
https://www.readbyqxmd.com/read/28505150/a-question-of-fate
#15
Mirjana Maletic-Savatic
Ever since the discovery of neural stem cells in the mammalian brain, the possibility of brain tissue regeneration has captured the minds of scientists, clinicians, and the public. Neural stem cells have been envisioned as a source of donor cells for transplantation and vectors for the delivery of gene therapy. Over the past decade, many researchers have contributed to characterizing these cells and their lineages, providing the foundation for their utilization as therapeutic devices. In a new study, Azim and colleagues took a different approach: using pharmacogenomics to focus on neural stem cell lineage, they identified specific compounds that can direct neural stem cell fate toward a specific lineage in vivo, both in physiological and pathological conditions...
May 2017: PLoS Biology
https://www.readbyqxmd.com/read/28498553/fundamentals-of-clinical-pharmacology-with-application-for-pregnant-women
#16
REVIEW
Avinash S Patil, Jessica Sheng, Sarah K Dotters-Katz, Maria S Schmoll, Mitchell Onslow, Rebecca C Pierson
Medication use is common in pregnancy, yet for most medications the optimal formulation and dosage have not been described specifically for pregnant women. Often, adverse effects are only discovered anecdotally or after extensive off-label use occurs. Since pharmacologic research that includes pregnant women is sparse and animal studies are often not applicable to the human fetus, providers must use knowledge of drug behavior and normal physiologic changes of pregnancy to personalize treatment for pregnant women...
May 12, 2017: Journal of Midwifery & Women's Health
https://www.readbyqxmd.com/read/28493098/personalized-therapeutics-and-pharmacogenomics-integral-to-personalized-health-care
#17
EDITORIAL
Wolfgang Sadee
No abstract text is available yet for this article.
May 10, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28491115/therapeutic-risk-and-benefits-of-concomitantly-using-herbal-medicines-and-conventional-medicines-from-the-perspectives-of-evidence-based-on-randomized-controlled-trials-and-clinical-risk-management
#18
REVIEW
Xiu-Lai Zhang, Meng Chen, Ling-Ling Zhu, Quan Zhou
Despite increased awareness of the potential of herb-drug interactions (HDIs), the lack of rigorous clinical evidence regarding the significance provides a challenge for clinicians and consumers to make rational decisions about the safe combination of herbal and conventional medicines. This review addressed HDIs based on evidence from randomized controlled trials (RCTs). Literature was identified by performing a PubMed search till January 2017. Risk description and clinical risk management were described. Among 74 finally included RCTs, 17 RCTs (22...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28490206/pharmacokinetics-pharmacodynamics-and-pharmacogenetics-associated-with-nonsteroidal-anti-inflammatory-drugs-and-opioids-in-pediatric-cancer-patients
#19
Jonathan Constance, Sarah Campbell, Amit A Somani, Venkata Yellepeddi, Katie Owens, Catherine Sherwin
Advancing appropriate and adequate analgesic pharmacotherapy in pediatric patients with cancer is an area of clinical need. Few studies have been performed to evaluate the selection of an analgesic and appropriate dosing corresponding to analgesic effect among pediatric cancer patients. This review describes information related to pharmacokinetic, pharmacodynamic, and pharmacogenomic (when applicable) considerations for analgesics that are commonly used to manage pain experienced by pediatric patients with cancer...
May 11, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28489317/pharmacogenomics-of-angiotensin-receptor-neprilysin-inhibitor-and-its-long-term-side-effects
#20
REVIEW
Chayakrit Krittanawong, Takeshi Kitai
The development of the promising agent sacubitril/valsartan, known as an angiotensin receptor blocker-neprilysin inhibitor (ARNI), to improve heart failure (HF) management, may benefit morbidity, mortality, and readmission rates in patients with HF. The PARADIGM-HF trial demonstrated that the ARNI can reduce morbidity and mortality in patients with heart failure with reduced ejection fraction (HFrEF), while ongoing PARAMOUNT and PARAGON-HF trials determined whether the ARNI has morbidity and mortality benefits in patients with heart failure with preserved ejection fraction (HFpEF)...
May 10, 2017: Cardiovascular Therapeutics
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