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Pharmacogenomic data

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https://www.readbyqxmd.com/read/28730340/cyp2d6-genotype-is-not-associated-with-survival-in-breast-cancer-patients-treated-with-tamoxifen-results-from-a-population-based-study
#1
D L Hertz, K M Kidwell, S G Hilsenbeck, S Oesterreich, C K Osborne, S Philips, C Chenault, R J Hartmaier, T C Skaar, M J Sikora, J M Rae
PURPOSE: A number of studies have tested the hypothesis that breast cancer patients with low-activity CYP2D6 genotypes achieve inferior benefit from tamoxifen treatment, putatively due to lack of metabolic activation to endoxifen. Studies have provided conflicting data, and meta-analyses suggest a small but significant increase in cancer recurrence, necessitating additional studies to allow for accurate effect assessment. We conducted a retrospective pharmacogenomic analysis of a prospectively collected community-based cohort of patients with estrogen receptor-positive breast cancer to test for associations between low-activity CYP2D6 genotype and disease outcome in 500 patients treated with adjuvant tamoxifen monotherapy and 500 who did not receive any systemic adjuvant therapy...
July 20, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28719597/pharmacogenomics-study-of-thiazide-diuretics-and-qt-interval-in-multi-ethnic-populations-the-cohorts-for-heart-and-aging-research-in-genomic-epidemiology
#2
A A Seyerle, C M Sitlani, R Noordam, S M Gogarten, J Li, X Li, D S Evans, F Sun, M A Laaksonen, A Isaacs, K Kristiansson, H M Highland, J D Stewart, T B Harris, S Trompet, J C Bis, G M Peloso, J A Brody, L Broer, E L Busch, Q Duan, A M Stilp, C J O'Donnell, P W Macfarlane, J S Floyd, J A Kors, H J Lin, R Li-Gao, T Sofer, R Méndez-Giráldez, S R Cummings, S R Heckbert, A Hofman, I Ford, Y Li, L J Launer, K Porthan, C Newton-Cheh, M D Napier, K F Kerr, A P Reiner, K M Rice, J Roach, B M Buckley, E Z Soliman, R de Mutsert, N Sotoodehnia, A G Uitterlinden, K E North, C R Lee, V Gudnason, T Stürmer, F R Rosendaal, K D Taylor, K L Wiggins, J G Wilson, Y-DI Chen, R C Kaplan, K Wilhelmsen, L A Cupples, V Salomaa, C van Duijn, J W Jukema, Y Liu, D O Mook-Kanamori, L A Lange, R S Vasan, A V Smith, B H Stricker, C C Laurie, J I Rotter, E A Whitsel, B M Psaty, C L Avery
Thiazide diuretics, commonly used antihypertensives, may cause QT interval (QT) prolongation, a risk factor for highly fatal and difficult to predict ventricular arrhythmias. We examined whether common single-nucleotide polymorphisms (SNPs) modified the association between thiazide use and QT or its component parts (QRS interval, JT interval) by performing ancestry-specific, trans-ethnic and cross-phenotype genome-wide analyses of European (66%), African American (15%) and Hispanic (19%) populations (N=78 199), leveraging longitudinal data, incorporating corrected standard errors to account for underestimation of interaction estimate variances and evaluating evidence for pathway enrichment...
July 18, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28711144/genetics-of-juvenile-idiopathic-arthritis
#3
REVIEW
Aimee O Hersh, Sampath Prahalad
Juvenile idiopathic arthritis (JIA) affects approximately 1 in 1000 US children. The cause of JIA is most likely multifactorial and due to an interplay of genetics and environmental factors. This article summarizes the known genetic risk factors for JIA that have been identified, and in some cases replicated, using a variety of methods, including genomewide association and candidate gene association studies. A brief discussion regarding pharmacogenomics and studies to data linking genetics to treatment response and outcomes is included...
August 2017: Rheumatic Diseases Clinics of North America
https://www.readbyqxmd.com/read/28708103/pharmacogenomics-of-targeted-agents-for-personalization-of-colorectal-cancer-treatment
#4
REVIEW
Alessia Bignucolo, Elena De Mattia, Erika Cecchin, Rossana Roncato, Giuseppe Toffoli
The use of targeted agents in the treatment of metastatic colorectal cancer (CRC) has improved patient outcomes. Anti-epidermal growth factor receptor (anti-EGFR) agents (cetuximab and panitumumab) and antiangiogenic molecules (bevacizumab, regorafeninb, ramucirumab, and aflibercept) have been successfully integrated into clinical practice. Other drugs have been designed to target additional deregulated pathways in CRC, such as MAPK (mitogen-activated protein kinase)/PI3K-AKT (phosphatidylinositol-3-kinase-AKT serine/threonine kinase)/mTOR (mammalian target of rapamycin), HER-2 and 3 ( human epidermal growth factor receptor-2 and -3), and BRAF...
July 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28704821/application-of-the-drugevar-database-in-cancer-genomics-and-pharmacogenomics
#5
Konstantinos Sarris, Angeliki Komianou, George P Patrinos, Theodora Katsila
In the post-genomic era, there is an increasing and urgent need for managing and visualizing big data. Data complexity and size will turn information growth into knowledge growth only if presented in a comprehensive and user-friendly way. In such a context, the information technology community collaborates in a multidisciplinary manner with other scientific fields searching for and/or developing tools and services for data management and visualization. We have previously developed DruGeVar, a comprehensive database that triangulates drugs with genes and pharmacogenomic biomarkers to serve clinical pharmacogenomics...
July 14, 2017: Public Health Genomics
https://www.readbyqxmd.com/read/28696416/cytochrome-p450-interactions-are-common-and-consequential-in-massachusetts-hospital-discharges
#6
T H McCoy, V M Castro, A Cagan, L Snapper, A Roberson, R H Perlis
Despite the recognition that drug-drug interactions contribute substantially to preventable health-care costs, the prevalence of such interactions related to the cytochrome P450 system in clinical practice remains poorly characterized. This study drew retrospective hospital discharge cohorts from a large health claims data set and a large health system data set. For every hospital discharge, frequency of co-occurrence of substrates and inducers or inhibitors at cytochrome P450 2D6, 2C19, 3A4 and 1A2 were determined...
July 11, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28696414/pharmacogenetics-of-oral-antidiabetes-drugs-evidence-for-diverse-signals-at-the-irs1-locus
#7
S Prudente, R Di Paola, S Pezzilli, M Garofolo, O Lamacchia, T Filardi, G C Mannino, L Mercuri, F Alberico, M G Scarale, G Sesti, S Morano, G Penno, M Cignarelli, M Copetti, V Trischitta
To investigate the role of IRS1 locus on failure to oral antidiabetes drugs (OADs) we genotyped single-nucleotide polymorphisms (SNPs), rs2943641, rs7578326 (tagging all SNPs genome-wide associated with type 2 diabetes (T2D) and related traits at this locus) and rs1801278 (that is, the loss-of-function IRS1 G972R amino acid substitution) in 2662 patients with T2D. Although no association with OAD failure was observed for rs2943641 and rs7578326 SNPs (odds ratio (OR): 1.04, 95% confidence interval (CI): 0.93-1...
July 11, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28689706/the-innovative-canadian-pharmacogenomic-screening-initiative-in-community-pharmacy-icanpic-study
#8
John Papastergiou, Peter Tolios, Wilson Li, Jane Li
OBJECTIVES: The safety and efficacy of medications can vary significantly between patients as a result of genetic variability. As genomic screening technologies become more widely available, pharmacists are ideally suited to use such tools to optimize medication therapy management. The objective of this study was to evaluate the feasibility of implementing personalized medication services into community pharmacy practice and to assess the number of drug therapy problems identified as a result of pharmacogenomic screening...
July 6, 2017: Journal of the American Pharmacists Association: JAPhA
https://www.readbyqxmd.com/read/28685396/pharmacokinetics-and-pharmacogenomics-of-bupropion-in-three-different-formulations-with-different-release-kinetics-in-healthy-human-volunteers
#9
Jamie N Connarn, Stephanie Flowers, Marisa Kelly, Ruijuan Luo, Kristen M Ward, Gloria Harrington, Ila Moncion, Masoud Kamali, Melivin McInnis, Meihua R Feng, Vicki Ellingrod, Andrew Babiskin, Xinyuan Zhang, Duxin Sun
The purpose of this pharmacokinetics (PK) study was to investigate whether different release kinetics from bupropion hydrochloride (HCl) immediate release (IR), sustained release (SR), and extended release (ER) formulations alter its metabolism and to test the hypothesis that the unsuccessful bioequivalence (BE) study of the higher strength (300 mg) of bupropion HCl ER tablets based on the successful BE study of the lower strength (150 mg) was due to metabolic saturation in the gastrointestinal (GI) lumen...
July 6, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28682531/florida-best-practice-psychotherapeutic-medication-guidelines-for-adults-with-major-depressive-disorder
#10
REVIEW
Roger S McIntyre, Trisha Suppes, Rajiv Tandon, Michael Ostacher
OBJECTIVE: Herein we provide the 2015 update for the Florida Best Practice Psychotherapeutic Medication Guidelines (FPG) for major depressive disorder (MDD). The FPG represent evidence-based decision support for practitioners providing care to adults with MDD. PARTICIPANTS: The consensus meeting included representatives from the Florida Agency for Health Care Administration (FAHCA), advocacy members, academic experts in MDD, and multidisciplinary mental health clinicians, as well as health policy experts...
June 2017: Journal of Clinical Psychiatry
https://www.readbyqxmd.com/read/28675654/bioinformatory-assisted-analysis-of-next-generation-sequencing-data-for-precision-medicine-in-pancreatic-cancer
#11
Linnéa Malgerud, Johan Lindberg, Valtteri Wirta, Maria Gustafsson-Liljefors, Masoud Karimi, Carlos Fernández Moro, Katrin Stecker, Alexander Picker, Carolin Huelsewig, Martin Stein, Regina Bohnert, Marco Del Chiaro, Stephan L Haas, Rainer L Heuchel, Johan Permert, Markus J Maeurer, Stephan Brock, Caroline S Verbeke, Lars Engstrand, David B Jackson, Henrik Grönberg, J-Matthias Löhr
Pancreatic ductal adenocarcinoma (PDAC) is a tumor with an extremely poor prognosis, predominantly due to chemotherapy resistance and numerous somatic mutations. Consequently, PDAC is a prime candidate for the use of sequencing to identify causative mutations, facilitating subsequent administration of targeted therapy. In a feasibility study, we retrospectively assessed the therapeutic recommendations of a novel, evidence-based software that analyzes Next-generation sequencing (NGS) data using a large panel of pharmacogenomic biomarkers for efficacy and toxicity...
July 4, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28672100/warfarin-pharmacogenomics-in-diverse-populations
#12
Justin B Kaye, Lauren E Schultz, Heidi E Steiner, Rick A Kittles, Larisa H Cavallari, Jason H Karnes
Genotype-guided warfarin dosing algorithms are a rational approach to optimize warfarin dosing and potentially reduce adverse drug events. Diverse populations, such as African-Americans (AAs) and Latinos, have greater variability in warfarin dose requirements and are at greater risk for experiencing warfarin-related adverse events compared with individuals of European ancestry. Although these data suggest that patients of diverse populations may benefit from improved warfarin dose estimation, the vast majority of literature on genotype-guided warfarin dosing, including data from prospective randomized trials, is in populations of European ancestry...
July 3, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28657381/safety-profile-of-biological-therapies-for-treating-rheumatoid-arthritis
#13
Juan D Cañete, Victoria Hernández, Raimon Sanmartí
Biological agents such as tumor necrosis factor inhibitors (TNFi), abatacept, rituximab and tocilizumab have proven efficacy in RA. However, these agents are also associated with adverse events so further data is essential to detect them at the earliest stage possible. Areas covered: Herein, the authors review the safety profile of biological therapy, including TNFi and non-TNF agents including abatacept (ABA), rituximab (RTX) and tocilizumab (TCZ). The authors analyze both published articles and congress communications including clinical trials, meta-analyses, observational studies, data from registries and spontaneous clinical reports...
June 28, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28655393/the-role-of-single-nucleotide-polymorphisms-of-cyp3a-and-abcb1-on-tacrolimus-predose-concentration-in-kidney-transplant-recipients
#14
Gregor Mlinšek, Vita Dolžan, Katja Goričar, Jadranka Buturović-Ponikvar, Miha Arnol
BACKGROUND: Tacrolimus has a narrow therapeutic drug window but high inter- and intrapatient variability. Our aim is to construct a model able to predict optimal maintenance tacrolimus predose concentration (C0) in kidney transplant patients. Here we present our study design and genotype and variant allele frequencies for the selected single nucleotide polymorphisms of genes involved in tacrolimus metabolism in our national cohort of kidney transplant recipients. METHODS: In the observational part of the study, we intend to determine allelic variants of CYP3A4, CYP3A5, and ABCB1 gene in a national cohort of 700 kidney transplants recipients...
June 28, 2017: Clinical Nephrology
https://www.readbyqxmd.com/read/28654165/using-personalized-medicine-in-the-management-of-diabetes-mellitus
#15
Nina Elk, Otito F Iwuchukwu
Diabetes mellitus is a worldwide problem of immense pharmacoeconomic burden. The multifactorial and complex nature of the disease lends itself to personalized pharmacotherapeutic approaches to treatment. Variability in individual risk and subsequent development of diabetes have been reported, in addition to differences in response to the many oral glucose lowering therapies currently available for diabetes pharmacotherapy. Pharmacogenomic studies have attempted to uncover the heritable components of individual variability in risk susceptibility and response to pharmacotherapy...
June 27, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28639505/rationale-and-design-of-the-multiethnic-pharmacogenomics-in-childhood-asthma-consortium
#16
Niloufar Farzan, Susanne J Vijverberg, Anand K Andiappan, Lambang Arianto, Vojko Berce, Natalia Blanca-López, Hans Bisgaard, Klaus Bønnelykke, Esteban G Burchard, Paloma Campo, Glorisa Canino, Bruce Carleton, Juan C Celedón, Fook Tim Chew, Wen Chin Chiang, Michelle M Cloutier, Denis Daley, Herman T Den Dekker, F Nicole Dijk, Liesbeth Duijts, Carlos Flores, Erick Forno, Daniel B Hawcutt, Natalia Hernandez-Pacheco, Johan C de Jongste, Michael Kabesch, Gerard H Koppelman, Vangelis G Manolopoulos, Erik Melén, Somnath Mukhopadhyay, Sara Nilsson, Colin N Palmer, Maria Pino-Yanes, Munir Pirmohamed, Uros Potočnki, Jan A Raaijmakers, Katja Repnik, Maximilian Schieck, Yang Yie Sio, Rosalind L Smyth, Csaba Szalai, Kelan G Tantisira, Steve Turner, Marc P van der Schee, Katia M Verhamme, Anke H Maitland-van der Zee
AIM: International collaboration is needed to enable large-scale pharmacogenomics studies in childhood asthma. Here, we describe the design of the Pharmacogenomics in Childhood Asthma (PiCA) consortium. MATERIALS & METHODS: Investigators of each study participating in PiCA provided data on the study characteristics by answering an online questionnaire. RESULTS: A total of 21 studies, including 14,227 children/young persons (58% male), from 12 different countries are currently enrolled in the PiCA consortium...
July 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28623316/revealing-protein-networks-and-gene-drug-connectivity-in-cancer-from-direct-information
#17
Xian-Li Jiang, Emmanuel Martinez-Ledesma, Faruck Morcos
The connection between genetic variation and drug response has long been explored to facilitate the optimization and personalization of cancer therapy. Crucial to the identification of drug response related genetic features is the ability to separate indirect correlations from direct correlations across abundant datasets with large number of variables. Here we analyzed proteomic and pharmacogenomic data in cancer tissues and cell lines using a global statistical model connecting protein pairs, genes and anti-cancer drugs...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28612644/methods-to-analyze-big-data-in-pharmacogenomics-research
#18
Ruowang Li, Dokyoon Kim, Marylyn D Ritchie
The scale and scope of pharmacogenomics research continues to expand as the cost and efficiency of molecular data generation techniques advance. These new technologies give rise to enormous opportunity for the identification of important genetic and genomic factors important for drug treatment response. With this opportunity come significant challenges. Most of these can be categorized as 'big data' issues, facing not only pharmacogenomics, but other fields in the life sciences as well. In this review, we describe some of the analysis techniques and tools being implemented for genetic/genomic discovery in pharmacogenomics...
June 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28607508/systematic-review-and-meta-analysis-pharmacogenetics-of-anti-tnf-treatment-response-in-rheumatoid-arthritis
#19
REVIEW
S Bek, A B Bojesen, J V Nielsen, J Sode, S Bank, U Vogel, V Andersen
Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects ~1% of the Caucasian population. Over the last decades, the availability of biological drugs targeting the proinflammatory cytokine tumour necrosis factor α, anti-TNF drugs, has improved the treatment of patients with RA. However, one-third of the patients do not respond to the treatment. We wanted to evaluate the status of pharmacogenomics of anti-TNF treatment. We performed a PubMed literature search and all studies reporting original data on associations between genetic variants and anti-TNF treatment response in RA patients were included and results evaluated by meta-analysis...
June 13, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28607505/predictive-genetic-markers-in-neoadjuvant-chemoradiotherapy-for-locally-advanced-esophageal-cancer-a-long-way-to-go-review-of-the-literature
#20
REVIEW
M Gusella, E Pezzolo, Y Modena, C Barile, D Menon, G Crepaldi, F La Russa, A P Fraccon, F Pasini
The role of genetic molecular markers in neoadjuvant treatment for locally advanced esophageal cancer has been reviewed, focusing strictly on concurrent chemoradiation protocols followed by surgery. Eleven studies evaluated the role of mRNA expression profile; the end point was overall survival (OS) in two studies and different definitions of histological response in nine. Genes reported as significant were involved in cell cycle control (30), apoptosis (7), structural molecules (9), cell metabolism (6) and DNA repair (1)...
June 13, 2017: Pharmacogenomics Journal
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