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Pharmacogenomics

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https://www.readbyqxmd.com/read/28217401/presence-of-arachidonoyl-carnitine-is-associated-with-adverse-cardiometabolic-responses-in-hypertensive-patients-treated-with-atenolol
#1
Liming Weng, Yan Gong, Jeffrey Culver, Stephen J Gardell, Christopher Petucci, Alison M Morse, Reginald F Frye, Stephen T Turner, Arlene Chapman, Eric Boerwinkle, John Gums, Amber L Beitelshees, Peggy R Borum, Julie A Johnson, Timothy J Garrett, Lauren M McIntyre, Rhonda M Cooper-DeHoff
INTRODUCTION: Atenolol, a commonly prescribed β blocker for hypertension, is also associated with adverse cardiometabolic effects such as hyperglycemia and dyslipidemia. Knowledge of the mechanistic underpinnings of these adverse effects of atenolol is incomplete. OBJECTIVE: We sought to identify biomarkers associated with risk for these untoward effects of atenolol. We measured baseline blood serum levels of acylcarnitines (ACs) that are involved in a host of different metabolic pathways, to establish associations with adverse cardiometabolic responses after atenolol treatment...
October 2016: Metabolomics: Open Access
https://www.readbyqxmd.com/read/28217400/novel-plasma-biomarker-of-atenolol-induced-hyperglycemia-identified-through-a-metabolomics-genomics-integrative-approach
#2
Felipe A de Oliveira, Mohamed H Shahin, Yan Gong, Caitrin W McDonough, Amber L Beitelshees, John G Gums, Arlene B Chapman, Eric Boerwinkle, Stephen T Turner, Reginald F Frye, Oliver Fiehn, Rima Kaddurah-Daouk, Julie A Johnson, Rhonda M Cooper-DeHoff
INTRODUCTION: While atenolol is an effective antihypertensive agent, its use is also associated with adverse events including hyperglycemia and incident diabetes that may offset the benefits of blood pressure lowering. By combining metabolomic and genomic data acquired from hypertensive individuals treated with atenolol, it may be possible to better understand the pathways that most impact the development of an adverse glycemic state. OBJECTIVE: To identify biomarkers that can help predict susceptibility to blood glucose excursions during exposure to atenolol...
August 2016: Metabolomics: Open Access
https://www.readbyqxmd.com/read/28215024/pharmacogenomics-of-platinum-based-chemotherapy-in-non-small-cell-lung-cancer-focusing-on-dna-repair-systems
#3
REVIEW
Yi Xiong, Bi-Yun Huang, Ji-Ye Yin
Drug therapy for non-small cell lung cancer consists mainly of platinum-based chemotherapy regimens. However, toxicity, drug resistance, and high risk of death have been seen in the clinic, which means there is a need for optimizing the use of medications. Platinum resistance could be mediated by a series of DNA repair pathways, and therefore, these pathways should be taken into account for optimizing drug using. The goal of pharmacogenomics is to elucidate genetic factors, such as DNA repair genes, which might underlie drug efficacy and effectiveness, and to improve therapeutic effects or guide personalized therapy as well...
April 2017: Medical Oncology
https://www.readbyqxmd.com/read/28214288/an-accelerator-mass-spectrometry-enabled-microtracer-study-to-evaluate-the-first-pass-effect-on-the-absorption-of-yh4808
#4
Anhye Kim, Byung-Yong Yu, Stephen R Dueker, Kwang-Hee Shin, Hwa Suk Kim, Hyungmi Ahn, Joo-Youn Cho, Kyung-Sang Yu, In-Jin Jang, Howard Lee
(14) C-labeled YH4808, a novel potassium-competitive acid blocker, was intravenously administered as a microtracer at 80 μg (11.8 kBq or 320 nCi) concomitantly with the non-radiolabeled oral drug at 200 mg to determine the absolute bioavailability and to assess the effect of pharmacogenomics on the oral absorption of YH4808. The absolute bioavailability was low and highly variable (mean, 10.1%; range, 2.3-19.3%), and M3 and M8, active metabolites of YH4808, were formed 22.6- and 38.5-fold higher after oral administration than intravenous administration, respectively...
February 18, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28213088/personalized-medicine-genetic-risk-prediction-of-drug-response
#5
REVIEW
Ge Zhang, Daniel W Nebert
Pharmacogenomics (PGx), a substantial component of "personalized medicine", seeks to understand each individual's genetic composition to optimize drug therapy -- maximizing beneficial drug response, while minimizing adverse drug reactions (ADRs). Drug responses are highly variable because innumerable factors contribute to ultimate phenotypic outcomes. Recent genome-wide PGx studies have provided some insight into genetic basis of variability in drug response. These can be grouped into three categories. [a] Monogenic (Mendelian) traits include early examples mostly of inherited disorders, and some severe (idiosyncratic) ADRs typically influenced by single rare coding variants...
February 14, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28212969/lessons-learned-when-introducing-pharmacogenomic-panel-testing-into-clinical-practice
#6
Marc B Rosenman, Brian Decker, Kenneth D Levy, Ann M Holmes, Victoria M Pratt, Michael T Eadon
OBJECTIVES: Implementing new programs to support precision medicine in clinical settings is a complex endeavor. We describe challenges and potential solutions based on the Indiana GENomics Implementation: an Opportunity for the Underserved (INGenious) program at Eskenazi Health-one of six sites supported by the Implementing GeNomics In pracTicE network grant of the National Institutes of Health/National Human Genome Research Institute. INGenious is an implementation of a panel of genomic tests...
January 2017: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/28210221/pharmacogenomic-characterization-and-isobologram-analysis-of-the-combination-of-ascorbic-acid-and-curcumin-two-main-metabolites-of-curcuma-longa-in-cancer-cells
#7
Edna Ooko, Onat Kadioglu, Henry J Greten, Thomas Efferth
Curcuma longa has long been used in China and India as anti-inflammatory agent to treat a wide variety of conditions and also as a spice for varied curry preparations. The chemoprofile of the Curcuma species exhibits the presence of varied phytochemicals with curcumin being present in all three species but AA only being shown in C. longa. This study explored the effect of a curcumin/AA combination on human cancer cell lines. The curcumin/AA combination was assessed by isobologram analysis using the Loewe additivity drug interaction model...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28207884/correction-a-european-spectrum-of-pharmacogenomic-biomarkers-implications-for-clinical-pharmacogenomics
#8
Clint Mizzi, Eleni Dalabira, Judit Kumuthini, Nduna Dzimiri, Istvan Balogh, Nazli Başak, Ruwen Böhm, Joseph Borg, Paola Borgiani, Nada Bozina, Henrike Bruckmueller, Beata Burzynska, Angel Carracedo, Ingolf Cascorbi, Constantinos Deltas, Vita Dolzan, Anthony Fenech, Godfrey Grech, Vytautas Kasiulevicius, Ľudevít Kádaši, Vaidutis Kučinskas, Elza Khusnutdinova, Yiannis L Loukas, Milan Macek, Halyna Makukh, Ron Mathijssen, Konstantinos Mitropoulos, Christina Mitropoulou, Giuseppe Novelli, Ioanna Papantoni, Sonja Pavlovic, Giuseppe Saglio, Jadranka Sertić, Maja Stojiljkovic, Andrew P Stubbs, Alessio Squassina, Maria Torres, Marek Turnovec, Ron H van Schaik, Konstantinos Voskarides, Salma M Wakil, Anneke Werk, Maria Del Zompo, Branka Zukic, Theodora Katsila, Ming Ta Michael Lee, Alison Motsinger-Rief, Howard L Mc Leod, Peter J van der Spek, George P Patrinos
[This corrects the article DOI: 10.1371/journal.pone.0162866.].
2017: PloS One
https://www.readbyqxmd.com/read/28202365/optimising-the-use-of-medicines-to-reduce-acute-kidney-injury-in-children-and-babies
#9
REVIEW
L Oni, D B Hawcutt, M A Turner, M W Beresford, S McWilliam, C Barton, B K Park, P Murray, B Wilm, I Copple, R Floyd, M Peak, A Sharma, D J Antoine
The majority of medications in children are administered in an unlicensed or off-label manner. Paediatricians are obliged to prescribe using the limited evidence available. The 2007 EU regulation on the use of paediatric drugs means pharmaceutical companies are now obliged to (and receive incentives for) contributing to paediatric drug data and carrying out paediatric clinical trials. This is important, as the efficacy and adverse effect profiles of medicines vary across childhood. Additionally, there are significant age-related changes in the pharmacodynamic and pharmacokinetic activity of many drugs...
February 12, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28188232/closed-tube-pcr-with-nested-serial-invasion-probe-visualization-using-gold-nanoparticles
#10
Jianping Wang, Bingjie Zou, Yinjiao Ma, Xueping Ma, Nan Sheng, Jianzhong Rui, Yang Shao, Guohua Zhou
BACKGROUND: Detecting DNA biomarkers related to personalized medicine could improve the outcome of drug therapy. However, personalized medicine in a resource-restrained hospital is very difficult because DNA biomarker detection should be performed by well-trained staff and requires expensive laboratory facilities. METHODS: We developed a gold nanoparticle-based "Tube-Lab" to enable DNA analysis in a closed tube. Gold nanoparticle-modified probes (GNPs) were used to construct an inexpensive and simple DNA sensor for signal readout...
February 10, 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/28187492/are-evidence-standards-different-for-genomic-vs-clinical-based-precision-medicine-a-quantitative-analysis-of-individualized-warfarin-therapy
#11
Devender S Dhanda, Gregory F Guzauskas, Josh J Carlson, Anirban Basu, David L Veenstra
Evidence requirements for implementation of precision medicine (PM), whether informed by genomic or clinical data, are not well defined. Evidence requirements are driven by uncertainty and its attendant consequences; these aspects can be quantified by a novel technique in health economics, value of information analysis (VOI). We utilized VOI analysis to compare the evidence levels over time for warfarin dosing based on pharmacogenomic- vs. amiodarone-warfarin drug-drug interaction information. The primary outcome was the expected value of perfect information (EVPI), which is an estimate of the upper limit of the societal value of conducting future research...
February 10, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28183252/pharmacological-profile-and-pharmacogenomics-of-anti-cancer-drugs-used-for-targeted-therapy
#12
Raffaele Di Francia, Angela De Monaco, Mariangela Saggese, Giancarla Iaccarino, Stefania Crisci, Ferdinando Frigeri, Rosaria De Filippi, Massimiliano Berretta, Antonio Pinto
Drugs for targeted therapies are primarily Small Molecules Inhibitors (SMIs), monoclonal antibodies (mAbs), interfering RNA molecules and microRNA. The use of these new agents generates a multifaceted step in the pharmacokinetics (PK) of these drugs. Individual PK variability is often large, and unpredictability observed in the response to the pharmacogenetic profile of the patient (e.g. cytochome P450 enzyme), patient characteristics such as adherence to treatment and environmental factors. Objective This review aims to overview the latest anticancer drugs eligible for targeted therapies and the most recent finding in pharmacogenomics related to toxicity/resistance because either individual gene polymorphisms or acquired mutation in a cancer cell...
February 8, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28177276/evaluating-the-association-of-multiple-single-nucleotide-polymorphisms-with-response-to-gemcitabine-and-platinum-combination-chemotherapy-in-urothelial-carcinoma-of-the%C3%A2-bladder%C3%A2
#13
Shaheen R Alanee, Sohela Shah, Emily C Zabor, Joseph Vijai, Irina Ostrovnaya, Ilana R Garcia-Grossman, Deepa V Pendse, Jason Littman, Ashley M Regazzi, Kenneth Offit, Dean F Bajorin
OBJECTIVE: To examine germline single nucleotide polymorphisms (SNPs) as markers of response to gemcitabine platinum (GP) combination chemotherapy in urothelial carcinoma (UC). METHODS: Saliva or blood was prospectively collected from 216 patients treated with GP for UC of the bladder between 1991 and 2011. Based on reported associations with gemcitabine and cisplatin response or putative mechanisms of gemcitabine or cisplatin/carboplatin activity, we selected SNPs of interest and were able to genotype 59 SNPs (using the SequenomMass ARRAYiPLEX platform) in 261 patients randomly split 2/3 into a training set (n = 174) and 1/3 into a test set (n = 87)...
March 2017: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28176639/personalized-medicine-in-the-paediatric-population-the-balance-between-pharmacogenetics-progress-and-bioethics
#14
Stefania Schiavone, Margherita Neri, Cristoforo Pomara, Irene Riezzo, Luigia Trabace, Emanuela Turillazzi
Personalized medicine (PM) is becoming increasingly important in contemporary clinical and research scenarios. In the context of PM, pharmacogenomics and pharmacogenetics are aimed at the genetic personalization of drug response. Extrinsic and intrinsic factors may explain inter-individual variability in drug response. Among such factors, age seems to specifically intervene to modulate drug response since normal developmental changes may influence the exposure-response relation. Consequently, the potential benefit of pharmacogenomics (PGx) in the paediatric population is considerable...
February 7, 2017: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/28176638/personalized-medicine-and-adverse-drug-reactions-the-experience-of-an-italian-teaching-hospital
#15
Raffaele La Russa, Vittorio Fineschi, Mariantonia Di Sanzo, Vittorio Gatto, Alessandro Santurro, Gabriella Martini, Matteo Scopetti, Paola Frati
The personalized medicine is a model of medicine based on inherent difference given by the genetic heritage that characterizes us, diversity that can affect also our response to administered therapy. Nowadays, the term "adverse drug reaction" is identified with any harmful effect involuntary resulting from the use of a medicinal product; pharmacogenomics, in this field, has the aim to improve the drug response and to reduce the adverse reaction. We analyzed all reports of adverse reaction collected in the Pharmacovigilance Centre database of an Italian University Hospital, at the Sant'Andrea Hospital Sapienza University of Rome, in a period of two years...
February 7, 2017: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/28173075/metformin-pharmacogenomics-a-genome-wide-association-study-to-identify-genetic-and-epigenetic-biomarkers-involved-in-metformin-anticancer-response-using-human-lymphoblastoid-cell-lines
#16
Nifang Niu, Tongzheng Liu, Junmei Cairns, Reynold C Ly, Xianglin Tan, Min Deng, Brooke L Fridley, Krishna R Kalari, Ryan P Abo, Gregory Jenkins, Anthony Batzler, Erin E Carlson, Poulami Barman, Sebastian Moran, Holger Heyn, Manel Esteller, Liewei Wang
No abstract text is available yet for this article.
November 1, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/28168945/psychiatric-pharmacogenomics-how-to-integrate-into-clinical-practice
#17
Stephen M Stahl
Pharmacogenomic testing can be integrated into modern mental health practices to help select psychotropic drugs for individuals who have failed first-line evidence-based treatments. This can be done by the process of "equipoise"-namely, balancing the weight of all available evidence. That evidence now includes not only diagnosis-specific treatment guidelines and "personalized" patient information, such as an individual's specific symptom profile, past response to medications, side effects, family history, and patient preference, but also "precision medicine," which incorporates the ever-expanding base of pharmacogenomic evidence for how an individual's own biomarkers alter the odds for that individual's treatment response or treatment intolerance...
February 2017: CNS Spectrums
https://www.readbyqxmd.com/read/28162244/pharmacogenetics-of-hypersensitivity-drug-reactions
#18
Simone Negrini, Laurent Becquemont
Adverse drug reactions are a significant cause of morbidity and mortality and represent a major burden on the healthcare system. Some of those reactions are immunologically mediated (hypersensitivity reactions) and can be clinically subdivided into two categories: immediate reactions (IgE-related) and delayed reactions (T-cell-mediated). Delayed hypersensitivity reactions include both systemic syndromes and organ-specific toxicities and can be triggered by a wide range of chemically diverse drugs. Recent studies have demonstrated a strong genetic association between human leukocyte antigen alleles and susceptibility to delayed drug hypersensitivity...
January 3, 2017: Thérapie
https://www.readbyqxmd.com/read/28161118/more-efficient-compliance-with-european-medicines-agency-and-food-and-drug-administration-regulations-for-pediatric-oncology-drug-development-problems-and-solutions
#19
Christopher-Paul Milne
5w?>The morbidity and mortality toll of pediatric cancer affects the public health of children worldwide, but despite the gains in the fight against cancer, more progress needs to take place against this disease, which is a leading cause of death and chronic disability in children. In response, leading regulatory authorities in the developed world have been ratcheting up their efforts to induce the private sector to expand their research and development focus during drug development for adult cancers to include children...
February 1, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28160554/pharmacogenetics-of-dipeptidyl-peptidase-4-inhibitors-in-a-taiwanese-population-with-type-2-diabetes
#20
Wen-Ling Liao, Wen-Jane Lee, Ching-Chu Chen, Chieh Hsiang Lu, Chien-Hsiun Chen, Yi-Chun Chou, I-Te Lee, Wayne H-H Sheu, Jer-Yuarn Wu, Chi-Fan Yang, Chung-Hsing Wang, Fuu-Jen Tsai
Dipeptidyl peptidase-4 (DPP-4) inhibitors are oral anti-hyperglycemic drugs enabling effective glycemic control in type 2 diabetes (T2D). Despite DPP-4 inhibitors' advantages, the patients' therapeutic response varies. In this retrospective cohort study, 171 Taiwanese patients with T2D were classified as sensitive or resistant to treatment based on the mean change in HbA1c levels. Using an assumption-free genome-wide association study, 45 single nucleotide polymorphisms (SNPs) involved in the therapeutic response to DPP-4 inhibitors (P < 1 × 10-4) were identified at or near PRKD1, CNTN3, ASK, and LOC10537792...
February 1, 2017: Oncotarget
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