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Pharmacogenomic data

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https://www.readbyqxmd.com/read/28514737/integration-of-phytochemicals-and-phytotherapy-into-cancer-precision-medicine
#1
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/28508787/the-importance-of-gene-drug-drug-interactions-in-pharmacogenomics-decision-support-an-analysis-based-on-austrian-claims-data
#2
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/28486096/key-pharmacogenomic-considerations-for-sickle-cell-disease-patients
#3
Alexandra Kolliopoulou, Apostolos Stratopoulos, Stavroula Siamoglou, Argyro Sgourou, Adamantia Papachatzopoulou, Theodora Katsila, George P Patrinos
Sickle cell disease (SCD), although a monogenic disease, exhibits a complex clinical phenotype that hampers optimum patient stratification and disease management, especially on hydroxyurea treatment. Moreover, theranostics, the combination of diagnostics to individualize and optimize therapeutic interventions, has not been firmly on the forefront of SCD research and clinical management to date. We suggest that if tailor-made theranostics in SCD is envisaged, pharmacogenomics is anticipated to be the way forward...
May 9, 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28485121/prophylaxis-of-migraine-headaches-with-riboflavin-a-systematic-review
#4
REVIEW
D F Thompson, H S Saluja
WHAT IS KNOWN AND OBJECTIVE: Migraine headache is a relatively common, debilitating condition that costs our healthcare system over 78 billion dollars per year. Riboflavin has been advocated as a safe, effective prophylactic therapy for the prevention of migraines. The purpose of this study was to provide a systematic review of the current role of riboflavin in the prophylaxis of migraine headache. METHODS: A MEDLINE literature search inclusive of the dates 1966-2016 was performed using the search terms: riboflavin and migraine disorders...
May 8, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/28468529/pharmacogenomics-in-pediatric-acute-lymphoblastic-leukemia-promises-and-limitations
#5
Zeina N Al-Mahayri, George P Patrinos, Bassam R Ali
Despite the significant advances achieved in pediatric acute lymphocytic leukemia (ALL) treatment, adverse side effects of drugs remain a challenging issue. Numerous ALL pharmacogenomic studies have been conducted to elucidate the predisposing genetic factors for their development. Plausible pharmacogenomic data are available for the osteonecrosis associated with glucocorticoids, the neurotoxicity associated with vincristine and the cardiotoxicity related to anthracyclines. However, these data have not been fully translated into the clinic due to several limitations, most importantly the lack of reliable evidence...
May 4, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28456840/rapid-evidence-review-of-the-comparative-effectiveness-harms-and-cost-effectiveness-of-pharmacogenomics-guided-antidepressant-treatment-versus-usual-care-for-major-depressive-disorder
#6
REVIEW
Kimberly Peterson, Eric Dieperink, Johanna Anderson, Erin Boundy, Lauren Ferguson, Mark Helfand
OBJECTIVE: This study aims to conduct an evidence review of the effectiveness, harms, and cost-effectiveness of pharmacogenomics-guided antidepressant treatment for major depressive disorder. METHODS: We searched MEDLINE®, the Cochrane Central Registry of Controlled Trials, and PsycINFO through February 2017. We used prespecified criteria to select studies, abstract data, and rate internal validity and strength of the evidence (PROSPERO number CRD42016036358). RESULTS: We included two randomized trials (RCT), five controlled cohort studies, and six modeling studies of mostly women in their mid-40s with few comorbidities...
April 29, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28451949/interaction-between-the-haptoglobin-genotype-and-vitamin-e-on-cardiovascular-disease-in-diabetes
#7
REVIEW
Irit Hochberg, Elliot M Berinstein, Uzi Milman, Chen Shapira, Andrew P Levy
PURPOSE OF REVIEW: Despite compelling evidence regarding the importance of oxidant stress in the development of vascular complications and observational studies suggesting that vitamin E may be protective from these complications, multiple clinical trials have failed to show benefit from vitamin E supplementation in the prevention of vascular complications in diabetes. One possible explanation for this failure of vitamin E may have been inappropriate patient selection. This review seeks to provide the clinical evidence and mechanistic basis for why a subset of individuals defined by their haptoglobin (Hp) genotype may derive cardiovascular protection by vitamin E supplementation...
June 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28440344/toxicogenomic-module-associations-with-pathogenesis-a-network-based-approach-to-understanding-drug-toxicity
#8
J J Sutherland, Y W Webster, J A Willy, G H Searfoss, K M Goldstein, A R Irizarry, D G Hall, J L Stevens
Despite investment in toxicogenomics, nonclinical safety studies are still used to predict clinical liabilities for new drug candidates. Network-based approaches for genomic analysis help overcome challenges with whole-genome transcriptional profiling using limited numbers of treatments for phenotypes of interest. Herein, we apply co-expression network analysis to safety assessment using rat liver gene expression data to define 415 modules, exhibiting unique transcriptional control, organized in a visual representation of the transcriptome (the 'TXG-MAP')...
April 25, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28440343/cyp3a4-genotype-is-associated-with-sildenafil-concentrations-in-patients-with-heart-failure-with-preserved-ejection-fraction
#9
S de Denus, J L Rouleau, D L Mann, G S Huggins, N L Pereira, S H Shah, T P Cappola, R Fouodjio, I Mongrain, M-P Dubé
Despite its established inter-individual variability, sildenafil has been the subject of only a few pharmacogenetic investigations, with limited data regarding the genetic modulators of its pharmacokinetics. We conducted a pharmacogenetic sub-study of patients randomized to sildenafil (n=85) in the RELAX trial, which investigated the impact of high-dose sildenafil in patients with heart failure with preserved left ventricular ejection fraction (HFpEF). In the overall population, the CYP3A4 inferred phenotype appeared associated with the dose-adjusted peak concentrations of sildenafil at week 12 and week 24 (adjusted P=0...
April 25, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28440342/significant-variation-between-snp-based-hla-imputations-in-diverse-populations-the-last-mile-is-the-hardest
#10
D J Pappas, A Lizee, V Paunic, K R Beutner, A Motyer, D Vukcevic, S Leslie, J Biesiada, J Meller, K D Taylor, X Zheng, L P Zhao, P-A Gourraud, J A Hollenbach, S J Mack, M Maiers
Four single nucleotide polymorphism (SNP)-based human leukocyte antigen (HLA) imputation methods (e-HLA, HIBAG, HLA*IMP:02 and MAGPrediction) were trained using 1000 Genomes SNP and HLA genotypes and assessed for their ability to accurately impute molecular HLA-A, -B, -C and -DRB1 genotypes in the Human Genome Diversity Project cell panel. Imputation concordance was high (>89%) across all methods for both HLA-A and HLA-C, but HLA-B and HLA-DRB1 proved generally difficult to impute. Overall, <27.8% of subjects were correctly imputed for all HLA loci by any method...
April 25, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28440341/quantitative-profiling-of-the-ugt-transcriptome-in-human-drug-metabolizing-tissues
#11
A Tourancheau, M Rouleau, S Guauque-Olarte, L Villeneuve, I Gilbert, A Droit, C Guillemette
Alternative splicing as a mean to control gene expression and diversify function is suspected to considerably influence drug response and clearance. We report the quantitative expression profiles of the human UGT genes including alternatively spliced variants not previously annotated established by deep RNA-sequencing in tissues of pharmacological importance. We reveal a comprehensive quantification of the alternative UGT transcriptome that differ across tissues and among individuals. Alternative transcripts that comprise novel in-frame sequences associated or not with truncations of the 5'- and/or 3'- termini, significantly contribute to the total expression levels of each UGT1 and UGT2 gene averaging 21% in normal tissues, with expression of UGT2 variants surpassing those of UGT1...
April 25, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28439573/systematic-review-of-cyclosporin-a-induced-%C3%A2-gingival-overgrowth-and-genetic-predisposition
#12
Georgios S Chatzopoulos, Vasiliki P Koidou, Larry F Wolff
OBJECTIVE: This systematic review aimed to investigate the influence of gene polymorphisms on the development of gingival overgrowth in renal transplant patients treated with cyclosporin A. METHOD AND MATERIALS: Electronic and hand literature searches were conducted by two independent reviewers in MEDLINE-Pubmed, Cochrane Library, ISI Web of Science, and SCOPUS Elsevier for prospective (case-control studies, cohort studies), cross-sectional, and retrospective studies published up to June 2016 (first week) in any language...
April 24, 2017: Quintessence International
https://www.readbyqxmd.com/read/28427468/learning-from-biomedical-linked-data-to-suggest-valid-pharmacogenes
#13
Kevin Dalleau, Yassine Marzougui, Sébastien Da Silva, Patrice Ringot, Ndeye Coumba Ndiaye, Adrien Coulet
BACKGROUND: A standard task in pharmacogenomics research is identifying genes that may be involved in drug response variability, i.e., pharmacogenes. Because genomic experiments tended to generate many false positives, computational approaches based on the use of background knowledge have been proposed. Until now, only molecular networks or the biomedical literature were used, whereas many other resources are available. METHOD: We propose here to consume a diverse and larger set of resources using linked data related either to genes, drugs or diseases...
April 20, 2017: Journal of Biomedical Semantics
https://www.readbyqxmd.com/read/28423632/the-genetic-variants-in-the-pten-pi3k-akt-pathway-predict-susceptibility-and-ce-a-f-chemotherapy-response-to-breast-cancer-and-clinical-outcomes
#14
Xiang Li, Ruishan Zhang, Zhuangkai Liu, Shuang Li, Hong Xu
The PI3K/PTEN/AKT pathway play a critical role in balancing cell growth and death. Epidemiologic studies suggested that mutations of the PI3K/PTEN/AKT pathway genes are associated with cancer risk, yet no data are available for PTEN rs701848, PIK3CA rs2699887, and AKT1 rs2494752 polymorphism and breast cancer(BC) risk. A case-control study was performed in 920 BC patients and 908 healthy controls using the TaqMan assay method. Overall, individuals with PTEN rs701848 TC, CC and TC/CC genotypes showed significant increased BC risk (P=0...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418010/interaction-between-nudt15-and-abcc4-variants-enhances-intolerability-of-6-mercaptopurine-in-japanese-patients-with-childhood-acute-lymphoblastic-leukemia
#15
Y Tanaka, H Nakadate, K Kondoh, K Nakamura, K Koh, A Manabe
6-Mercaptopurine (6-MP) is a main component of childhood acute lymphoblastic leukemia (ALL) treatment. Some candidate gene variants are associated with its toxicities, but the major variants and effects of combined variants remain unclear. We used Cox regression analysis to evaluate the time-dependent association between candidate variants and the cumulative incidence of 6-MP intolerability in 95 Japanese patients. The major risk factors for severe leukopenia were ABCC4 rs3765534, NUDT15 rs116855232 and rs186364861 in multi-covariate analysis (P<0...
April 18, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28401703/tacrolimus-population-pharmacokinetics-according-to-cyp3a5-genotype-and-clinical-factors-in-chinese-adult-kidney-transplant-recipients
#16
REVIEW
H J Zhang, D Y Li, H J Zhu, Y Fang, T S Liu
WHAT IS KNOWN AND OBJECTIVES: Tacrolimus is characterized by a narrow therapeutic index and a considerable inter- and intraindividual pharmacokinetic variability. The aim of our study was to develop a population pharmacokinetic model of tacrolimus in adult kidney transplant of Chinese patients, identify factors especially CYP3A5*3 genetic polymorphism that explain variability, and determine dosage regimens. METHODS: Pharmacogenomic data obtained from 83 Chinese kidney transplant patients treated with tacrolimus were determined using polymerase chain reaction-restriction fragment length polymorphism analysis...
April 11, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/28398356/snp-based-hla-allele-tagging-imputation-and-association-with-antiepileptic-drug-induced-cutaneous-reactions-in-hong-kong-han-chinese
#17
H Gui, M Kwok, L Baum, P C Sham, P Kwan, S S Cherny
Human leukocyte antigen (HLA) genes control the regulation of the human immune system and are involved in immune-related diseases. Population surveys on relationships between single nucleotide polymorphisms (SNP) and HLA alleles are essential to conduct genetic association between HLA variants and diseases. Samples were obtained from our in-house database for epilepsy genetics and pharmacogenetics research. Using 184 epilepsy patients with both genome-wide SNP array and HLA-A/B candidate gene sequencing data, we sought tagging SNPs that completely represent sixHLA risk alleles; in addition, a Hong Kong population-specific reference panel was constructed for SNP-based HLA imputation...
April 11, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28398354/global-genetic-variation-of-select-opiate-metabolism-genes-in-self-reported-healthy-individuals
#18
F R Wendt, G Pathak, A Sajantila, R Chakraborty, B Budowle
CYP2D6 is a key pharmacogene encoding an enzyme impacting poor, intermediate, extensive and ultrarapid phase I metabolism of many marketed drugs. The pharmacogenetics of opiate drug metabolism is particularly interesting due to the relatively high incidence of addiction and overdose. Recently, trans-acting opiate metabolism and analgesic response enzymes (UGT2B7, ABCB1, OPRM1 and COMT) have been incorporated into pharmacogenetic studies to generate more comprehensive metabolic profiles of patients. With use of massively parallel sequencing, it is possible to identify additional polymorphisms that fine tune, or redefine, previous pharmacogenetic findings, which typically rely on targeted approaches...
April 11, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28345177/pharmacogenomics-of-off-target-adverse-drug-reactions
#19
REVIEW
Sarah L Garon, Rebecca K Pavlos, Katie D White, Nancy J Brown, Cosby A Stone, Elizabeth J Phillips
Off-target adverse drug reactions (ADRs) are associated with significant morbidity and costs to the healthcare system, and their occurrence is not predictable based on the known pharmacological action of the drug's therapeutic effect. Off-target ADRs may or may not be associated with immunological memory, although they can manifest with a variety of shared clinical features, including maculopapular exanthema, severe cutaneous adverse reactions (SCARs), angioedema, pruritus and bronchospasm. Discovery of specific genes associated with a particular ADR phenotype is a foundational component of clinical translation into screening programmes for their prevention...
March 26, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28327186/clinical-behavioural-and-pharmacogenomic-factors-influencing-the-response-to-levothyroxine-therapy-in-patients-with-primary-hypothyroidism-protocol-for-a-systematic-review
#20
Rosie Dew, Onyebuchi Okosieme, Colin Dayan, Vinay Eligar, Ishrat Khan, Salman Razvi, Simon Pearce, Scott Wilkes
BACKGROUND: Suboptimal thyroid hormone therapy including under-replacement and over-replacement is common amongst patients with hypothyroidism. This is a significant health concern as affected patients are at risk of adverse cardiovascular or metabolic consequences. Despite a growing body of evidence on the effects of various factors on thyroid hormone replacement, a systematic appraisal of the evidence is lacking. This review aims to appraise and quantify the extent to which clinical, behavioural and pharmacogenomic factors affect levothyroxine therapy in patients with primary hypothyroidism...
March 21, 2017: Systematic Reviews
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