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https://www.readbyqxmd.com/read/28217400/novel-plasma-biomarker-of-atenolol-induced-hyperglycemia-identified-through-a-metabolomics-genomics-integrative-approach
#1
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
#2
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/28202365/optimising-the-use-of-medicines-to-reduce-acute-kidney-injury-in-children-and-babies
#3
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/28187492/are-evidence-standards-different-for-genomic-vs-clinical-based-precision-medicine-a-quantitative-analysis-of-individualized-warfarin-therapy
#4
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/28176639/personalized-medicine-in-the-paediatric-population-the-balance-between-pharmacogenetics-progress-and-bioethics
#5
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
#6
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/28161118/more-efficient-compliance-with-european-medicines-agency-and-food-and-drug-administration-regulations-for-pediatric-oncology-drug-development-problems-and-solutions
#7
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
#8
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
https://www.readbyqxmd.com/read/28131654/effects-of-udp-glucuronosyltransferase-ugt-polymorphisms-on-the-pharmacokinetics-of-febuxostat-in-healthy-chinese-volunteers
#9
Meihua Lin, Jian Liu, Huili Zhou, Minglan Wu, Duo Lv, Yujie Huang, Yunliang Zheng, Jianzhong Shentu, Lihua Wu
The pharmacokinetics (PKs) of febuxostat varies among individuals, while the main causes are still unknown. We investigated whether the polymorphisms of UGT1A1 and UGT1A3 played an important role in the disposition of the drug after oral administration of febuxostat tablet in Chinese subjects. A total of 42 healthy subjects were from two previous independent clinical bioequivalence (BE) trials of febuxostat, in which the same reference formulation (ULORIC(®) tablet, 80 mg) was taken, and thus the PK data were combined for the evaluation of pharmacogenomic effect on febuxostat PKs...
August 20, 2016: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28117005/pharmacogenomic-challenges-in-cardiovascular-diseases-examples-of-drugs-and-considerations-for-future-integration-in-clinical-practice
#10
Jérôme Chatelin, Maria G Stathopoulou, Alex-Ander Aldasoro Arguinano, Ting Xie, Sophie Visvikis-Siest
Introduction Even if cardiovascular disease (CVD) drugs are supported by high level proofs, the results of CVD treatment present great disparities: there are still patients dying with supposed optimal treatment, patients facing adverse events and CVD remain the primary cause of death in the world. Pharmacogenomics is the basis of personalisation of the treatment able to allow higher medication success rates. In this review, we will present detailed examples of CVD drugs to highlight the complexity of this challenging field and we will discuss novel concepts that should be considered for a fastest integration of pharmacogenomics in clinical practice of CVD...
January 23, 2017: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/28099754/addressing-the-crisis-in-the-treatment-of-osteoporosis-a-path-forward
#11
Sundeep Khosla, Jane A Cauley, Juliet Compston, Douglas P Kiel, Clifford Rosen, Kenneth G Saag, Elizabeth Shane
Considerable data and media attention have highlighted a potential "crisis" in the treatment of osteoporosis. Specifically, despite the availability of several effective drugs to prevent fractures, many patients who need pharmacological therapy are either not being prescribed these medications or if prescribed a medication, are simply not taking it. Although there are many reasons for this "gap" in the treatment of osteoporosis, a major factor is physician and patient concerns over the risk of side effects, especially atypical femur fractures (AFFs) related to bisphosphonate (and perhaps other antiresorptive) drug therapy...
December 29, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28096076/a-landscape-of-synthetic-viable-interactions-in-cancer
#12
Yunyan Gu, Ruiping Wang, Yue Han, Wenbin Zhou, Zhangxiang Zhao, Tingting Chen, Yuanyuan Zhang, Fuduan Peng, Haihai Liang, Lishuang Qi, Wenyuan Zhao, Da Yang, Zheng Guo
Synthetic viability, which is defined as the combination of gene alterations that can rescue the lethal effects of a single gene alteration, may represent a mechanism by which cancer cells resist targeted drugs. Approaches to detect synthetic viable (SV) interactions in cancer genome to investigate drug resistance are still scarce. Here, we present a computational method to detect synthetic viability-induced drug resistance (SVDR) by integrating the multidimensional data sets, including copy number alteration, whole-exome mutation, expression profile and clinical data...
January 17, 2017: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/28073152/characterizing-pharmacogenomic-guided-medication-use-with-a-clinical-data-repository
#13
Patrick C Mathias, Nathaniel Hendrix, Wei-Jhih Wang, Katelyn Keyloun, Maher Khelifi, Peter Tarczy-Hornoch, Beth Devine
The extent to which pharmacogenomic-guided medication use has been adopted in various health systems is unclear. To assess the uptake of pharmacogenomic-guided medication use, we determined its frequency across our health system, which does not have a structured testing program. Using a multi-site clinical data repository, we identified adult patients' first prescribed medications between January 2011 and December 2013 and investigated the frequency of germline and somatic pharmacogenomic testing, by PharmGKB level of FDA label information...
January 10, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28068459/does-pharmacogenomic-testing-improve-clinical-outcomes-for-major-depressive-disorder-a-systematic-review-of-clinical-trials-and-cost-effectiveness-studies
#14
Joshua D Rosenblat, Yena Lee, Roger S McIntyre
OBJECTIVE: Pharmacogenomic testing has become scalable and available to the general public. Pharmacogenomics has shown promise for predicting antidepressant response and tolerability in the treatment of major depressive disorder (MDD). In theory, pharmacogenomics can improve clinical outcomes by guiding antidepressant selection and dosing. The current systematic review examines the extant literature to determine the impact of pharmacogenomic testing on clinical outcomes in MDD and assesses its cost-effectiveness...
January 3, 2017: Journal of Clinical Psychiatry
https://www.readbyqxmd.com/read/28051073/psychological-and-behavioural-impact-of-returning-personal-results-from-whole-genome-sequencing-the-healthseq-project
#15
Saskia C Sanderson, Michael D Linderman, Sabrina A Suckiel, Randi Zinberg, Melissa Wasserstein, Andrew Kasarskis, George A Diaz, Eric E Schadt
Providing ostensibly healthy individuals with personal results from whole-genome sequencing could lead to improved health and well-being via enhanced disease risk prediction, prevention, and diagnosis, but also poses practical and ethical challenges. Understanding how individuals react psychologically and behaviourally will be key in assessing the potential utility of personal whole-genome sequencing. We conducted an exploratory longitudinal cohort study in which quantitative surveys and in-depth qualitative interviews were conducted before and after personal results were returned to individuals who underwent whole-genome sequencing...
February 2017: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/28045129/the-glutathione-transferase-mu-null-genotype-leads-to-lower-6-mmpr-levels-in-patients-treated-with-azathioprine-but-not-with-mercaptopurine
#16
M M T J Broekman, D R Wong, G J A Wanten, H M Roelofs, C J van Marrewijk, O H Klungel, A L M Verbeek, P M Hooymans, H-J Guchelaar, H Scheffer, L J J Derijks, M J H Coenen, D J de Jong
The conversion of azathioprine (AZA) to mercaptopurine (MP) is mediated by glutathione transferase Mu1 (GSTM1), alpha1 (GSTA1) and alpha2 (GSTA2). We designed a case-control study with data from the TOPIC trial to explore the effects of genetic variation on steady state 6-methylmercaptopurine ribonucleotide (6-MMPR) and 6-thioguanine nucleotide (6-TGN) metabolite levels. We included 199 patients with inflammatory bowel disease (126 on AZA and 73 on MP). GSTM1-null genotype carriers on AZA had two-fold lower 6-MMPR levels than AZA users carrying one or two copies of GSTM1 (2239 (1006-4587) versus 4371 (1897-7369) pmol/8 × 10(8) RBCs; P<0...
January 3, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28044932/ubiquitous-pharmacogenomics-u-pgx-the-time-for-implementation-is-now-an-horizon2020-program-to-drive-pharmacogenomics-into-clinical-practice
#17
Erika Cecchin, Rossana Roncato, Hendrik Jan Guchelaar, Giuseppe Toffoli, and for the Ubiquitous Pharmacogenomics Consortium
Although the clinical validity of a number of pharmacogenetic markers is nowadays a matter of fact, and led authoritative scientific consortia as the Dutch Pharmacogenetic Working Group (DPWG) and the Clinical Pharmacogenomics Implementation Consortium (CPIC) to publish pharmacogenetic guidelines, the clinical implementation in the real life remains challenging. Ubiquitous Pharmacogenomics (U-PGx) program is a coordinated effort that put together scientific and clinical expertise in the pharmacogenomic field, to implement the pre-emptive pharmacogenomic approach in the clinical practice in Europe, and to demonstrate its benefit in both patients clinical outcome and quality of life, with an economic advantage for the healthcare system...
2, 2017: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/28032660/addressing-the-crisis-in-the-treatment-of-osteoporosis-a-path-forward
#18
Sundeep Khosla, Jane A Cauley, Juliet Compston, Douglas P Kiel, Clifford Rosen, Kenneth G Saag, Elizabeth Shane
Considerable data and media attention have highlighted a potential "crisis" in the treatment of osteoporosis. Specifically, despite the availability of several effective drugs to prevent fractures, many patients who need pharmacological therapy are either not being prescribed these medications or if prescribed a medication, are simply not taking it. Although there are many reasons for this "gap" in the treatment of osteoporosis, a major factor is physician and patient concerns over the risk of side effects, especially atypical femur fractures (AFFs) related to bisphosphonate (and perhaps other anti-resorptive) drug therapy...
December 29, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28007021/implementation-of-next-generation-sequencing-into-pediatric-hematology-oncology-practice-moving-beyond-actionable-alterations
#19
Jennifer A Oberg, Julia L Glade Bender, Maria Luisa Sulis, Danielle Pendrick, Anthony N Sireci, Susan J Hsiao, Andrew T Turk, Filemon S Dela Cruz, Hanina Hibshoosh, Helen Remotti, Rebecca J Zylber, Jiuhong Pang, Daniel Diolaiti, Carrie Koval, Stuart J Andrews, James H Garvin, Darrell J Yamashiro, Wendy K Chung, Stephen G Emerson, Peter L Nagy, Mahesh M Mansukhani, Andrew L Kung
BACKGROUND: Molecular characterization has the potential to advance the management of pediatric cancer and high-risk hematologic disease. The clinical integration of genome sequencing into standard clinical practice has been limited and the potential utility of genome sequencing to identify clinically impactful information beyond targetable alterations has been underestimated. METHODS: The Precision in Pediatric Sequencing (PIPseq) Program at Columbia University Medical Center instituted prospective clinical next generation sequencing (NGS) for pediatric cancer and hematologic disorders at risk for treatment failure...
December 23, 2016: Genome Medicine
https://www.readbyqxmd.com/read/27997009/-genomics-of-lung-adenocarcinoma-pathogenetic-significance-and-clinical-applications
#20
Raffaele Palmirotta, Silvana Acquafredda, Antonella Argentiero, Claudia Carella, Laura Lanotte, Nicla Pappagallo, Davide Quaresmini, Franco Silvestris
Diagnostic and therapeutic approaches to non small cell lung cancer (NSCLC), especially adenocarcinoma, have recently undergone dramatic evolution according to the tremendous amount of molecular data collected on this cancer. In fact, the application of oncogenomics has identified novel molecular subtypes of NSCLC and led the way to diagnostic criteria based on the expression of specific genetic alterations that can provide prognostic and specific indications to the molecular targeted therapies. In NSCLC, several genes show "driver" molecular alterations that confer oncogenic potential to progenitor cells through the enrollment of metabolic pathways critical for cell proliferation and tumor development...
December 2016: Recenti Progressi in Medicina
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