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Pharmacogenomics

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https://www.readbyqxmd.com/read/28933291/pharmacotranscriptomic-biomarkers-in-glucocorticoid-treatment-of-pediatric-inflammatory-bowel-disease
#1
Marianna Lucafò, Biljana Stankovic, Nikola Kotur, Alessia Di Silvestre, Stefano Martelossi, Alessandro Ventura, Branka Zukic, Sonya Pavlovic, Giuliana Decorti
Pharmacotranscriptomics aims to reach more accurate drug dosing based on interindividual transcriptome variations. Here, we provide an overview of RNA biomarkers that could predict the response to glucocorticoids (GCs), considered the standard for treatment of inflammatory bowel diseases (IBD), both in adult and pediatric patients. Although new biological agents are very effective in the IBD treatment, GCs are still widely used for induction of remission in IBD patients with moderate to severe disease. It is important to identify patients that are poor responders to GCs therapy, because suboptimal response is frequent and associated with various side effects...
September 20, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28930612/genetic-addiction-risk-score-gars-%C3%A2-a-predictor-of-vulnerability-to-opioid-dependence
#2
Kenneth Blum, Amanda L C Chen, Panayotis K Thanos, Marcelo Febo, Zsolt Demetrovics, Kristina Dushaj, Abraham Kovoor, David Baron, David E Smith, Alphonso Kenison Roy Iii, Lyle Fried, Thomas J H Chen, Edwin Chapman, Edward Modestino, Bruce Steinberg, Rajendra D Badgaiyan
The interaction of neurotransmitters and genes that control the release of dopamine is the Brain Reward Cascade (BRC). Variations within the BRC, whether genetic or epigenetic, may predispose individuals to addictive behaviors and altered pain tolerance. This discussion authored by a group of concerned scientists and clinicians examines the Genetic Addiction Risk Score (GARS), the first test to accurately predict vulnerability to pain, addiction, and other compulsive behaviors, defined as Reward Deficiency Syndrome (RDS)...
January 1, 2018: Frontiers in Bioscience (Elite Edition)
https://www.readbyqxmd.com/read/28921648/rna-therapeutics-in-oncology-advances-challenges-and-future-directions
#3
A Robert MacLeod, Stanley T Crooke
RNA-based therapeutic technologies represent a rapidly expanding class of therapeutic opportunities with the power to modulate cellular biology in ways never before possible. With RNA-targeted therapeutics, inhibitors of previously undruggable proteins, gene expression modulators, and even therapeutic proteins can be rationally designed based on sequence information alone, something that is not possible with other therapeutic modalities. The most advanced RNA therapeutic modalities are antisense oligonucleotides (ASOs) and small interfering RNAs...
October 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28921647/pharmacogenomics-implementation-at-the-national-institutes-of-health-clinical-center
#4
Tristan M Sissung, Jon W McKeeby, Jharana Patel, Juan J Lertora, Parag Kumar, Willy A Flegel, Sharon D Adams, Ellen J Eckes, Frank Mickey, Teri M Plona, Stephanie D Mellot, Ryan N Baugher, Xiaolin Wu, Daniel R Soppet, Mary E Barcus, Vivekananda Datta, Kristen M Pike, Gary DiPatrizio, William D Figg, Barry R Goldspiel
The National Institutes of Health Clinical Center (NIH CC) is the largest hospital in the United States devoted entirely to clinical research, with a highly diverse spectrum of patients. Patient safety and clinical quality are major goals of the hospital, and therapy is often complicated by multiple cotherapies and comorbidities. To this end, we implemented a pharmacogenomics program in 2 phases. In the first phase, we implemented genotyping for HLA-A and HLA-B gene variations with clinical decision support (CDS) for abacavir, carbamazepine, and allopurinol...
October 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28921458/pharmacogenetics-and-pharmacogenomics-in-moderate-to-severe-psoriasis
#5
REVIEW
María C Ovejero-Benito, Ester Muñoz-Aceituno, Alejandra Reolid, Miriam Saiz-Rodríguez, Francisco Abad-Santos, Esteban Daudén
Pharmacogenetics is the study of variations in DNA sequence related to drug response. Moreover, the evolution of biotechnology and the sequencing of human DNA have allowed the creation of pharmacogenomics, a branch of genetics that analyzes human genes, the RNAs and proteins encoded by them, and the inter-and intra-individual variations in expression and function in relation to drug response. Pharmacogenetics and pharmacogenomics are being used to search for biomarkers that can predict response to systemic treatments, including those for moderate-to-severe psoriasis...
September 18, 2017: American Journal of Clinical Dermatology
https://www.readbyqxmd.com/read/28918937/a-predictive-model-for-selective-targeting-of-the-warburg-effect-through-gapdh-inhibition-with-a-natural-product
#6
Maria V Liberti, Ziwei Dai, Suzanne E Wardell, Joshua A Baccile, Xiaojing Liu, Xia Gao, Robert Baldi, Mahya Mehrmohamadi, Marc O Johnson, Neel S Madhukar, Alexander A Shestov, Iok I Christine Chio, Olivier Elemento, Jeffrey C Rathmell, Frank C Schroeder, Donald P McDonnell, Jason W Locasale
Targeted cancer therapies that use genetics are successful, but principles for selectively targeting tumor metabolism that is also dependent on the environment remain unknown. We now show that differences in rate-controlling enzymes during the Warburg effect (WE), the most prominent hallmark of cancer cell metabolism, can be used to predict a response to targeting glucose metabolism. We establish a natural product, koningic acid (KA), to be a selective inhibitor of GAPDH, an enzyme we characterize to have differential control properties over metabolism during the WE...
September 8, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28916927/genetic-test-risk-prediction-and-counseling
#7
Maggie Haitian Wang, Haoyi Weng
Advancement in technology has nurtured the new era of genetic tests for personalized medicine. In this chapter, we will introduce the current development, challenges, and the outlook of genetic test, disease risk prediction, and genetic counseling. In the first section, we will present the success cases in the areas of molecular classification of tumors, pharmacogenomics, and Mendelian disorders, and the challenges of genetic tests implementations. In the second section, common methods for genetic risk prediction models and evaluation measures will be introduced, as well as challenges in feature reliability, risk model stability, and clinical utility...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28904393/microrna-pharmacogenomics-based-integrated-model-of-mir-17-92-cluster-in-sorafenib-resistant-hcc-cells-reveals-a-strategy-to-forestall-drug-resistance
#8
Faryal Mehwish Awan, Anam Naz, Ayesha Obaid, Aqsa Ikram, Amjad Ali, Jamil Ahmad, Abdul Khaliq Naveed, Hussnain Ahmed Janjua
Among solid tumors, hepatocellular carcinoma (HCC) emerges as a prototypical therapy-resistant tumor. Considering the emerging sorafenib resistance crisis in HCC, future studies are urgently required to overcome resistance. Recently noncoding RNAs (ncRNAs) have emerged as significant regulators in signalling pathways involved in cancer drug resistance and pharmacologically targeting these ncRNAs might be a novel stratagem to reverse drug resistance. In the current study, using a hybrid Petri net based computational model, we have investigated the harmonious effect of miR-17-92 cluster inhibitors/mimics and circular RNAs on sorafenib resistant HCC cells in order to explore potential resistance mechanisms and to identify putative targets for sorafenib-resistant HCC cells...
September 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28901847/micrornas-to-monitor-pain-migraine-and-drug-treatment
#9
Luca Gallelli, Erika Cione, Maria Cristina Caroleo, Marco Carotenuto, Pasqualina Lagana, Antonio Siniscalchi, Vincenzo Guidetti
Migraine is a prevalent neurovascular disorders with a complex pathophysiology and therapeutic options characterized by important side effects or problems related to drug abuse. No specific biomarkers are recognized to be univocal for this subclinical condition, yet. In this concern microRNAs have been suggested as potentially useful screening/diagnostic tool, and research is underway to recognize the most effective candidate(s). microRNAs, able to regulate immune and neuronal processes are herein reported for both, mice models with multiple induced pain conditions and human subjects...
September 12, 2017: MicroRNA
https://www.readbyqxmd.com/read/28900583/the-daniel-k-inouye-college-of-pharmacy-scripts-precision-medicine-through-the-use-of-pharmacogenomics-current-status-and-barriers-to-implementation
#10
Anita E Ciarleglio, Carolyn Ma
The precision medicine initiative brought forth by President Barack Obama in 2015 is an important step on the journey to truly personalized medicine. A broad knowledge and understanding of the implications of the pharmacogenomic literature will be critical to the achievement of this goal. While a great amount of data has been published in the areas of pharmacogenomics and pharmacogenetics, there are still relatively few instances in which the need for clinical intervention can be stated without doubt, and which are widely accepted and practiced by the medical community...
September 2017: Hawai'i Journal of Medicine & Public Health: a Journal of Asia Pacific Medicine & Public Health
https://www.readbyqxmd.com/read/28900181/heterogeneity-aware-random-forest-for-drug-sensitivity-prediction
#11
Raziur Rahman, Kevin Matlock, Souparno Ghosh, Ranadip Pal
Samples collected in pharmacogenomics databases typically belong to various cancer types. For designing a drug sensitivity predictive model from such a database, a natural question arises whether a model trained on diverse inter-tumor heterogeneous samples will perform similar to a predictive model that takes into consideration the heterogeneity of the samples in model training and prediction. We explore this hypothesis and observe that ensemble model predictions obtained when cancer type is known out-perform predictions when that information is withheld even when the samples sizes for the former is considerably lower than the combined sample size...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28899477/-research-advances-in-pharmacogenomics-of-mercaptopurine
#12
Xiao-Xiao Chen, Shu-Hong Shen
Mercaptopurine is a common chemotherapeutic drug and immunosuppressive agent and plays an important role in the treatment of acute lymphoblastic leukemia and inflammatory bowel disease. It may cause severe adverse effects such as myelosuppression, which may result in the interruption of treatment or complications including infection or even threaten patients' lives. However, the adverse effects of mercaptopurine show significant racial and individual differences, which reveal the important role of genetic diversity...
September 2017: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/28891702/pharmacokinetics-of-a-sustained-release-formulation-of-meloxicam-after-subcutaneous-administration-to-hispaniolan-amazon-parrots-amazona-ventralis
#13
David Sanchez-Migallon Guzman, Michael H Court, Zhaohui Zhu, Noémie Summa, Joanne R Paul-Murphy
Meloxicam has been shown to have a safe and favorable pharmacodynamic profile with individual variability in Hispaniolan Amazon parrots (Amazona ventralis). In the current study, we determined the pharmacokinetics of a sustained-release formulation of meloxicam after subcutaneous administration to Hispaniolan Amazon parrots. Twelve healthy adult parrots, 6 males and 6 females, were used in the study. Blood samples were collected before (time 0) and at 0.5, 1, 2, 6, 12, 24, 48, 72, 96, and 120 hours after a single dose of the sustained-release meloxicam formulation (3 mg/kg SC)...
September 2017: Journal of Avian Medicine and Surgery
https://www.readbyqxmd.com/read/28891449/role-of-pharmacogenomics-in-antiepileptic-drug-therapy-current-status-and-future-perspectives
#14
Antonio Gambardella, Angelo Labate, Laura Mumoli, Iscia Lopes-Cendes, Fernando Cendes
BACKGROUND: Growing evidence indicates that pharmacogenomics will positively impact treatment for patients with epilepsy in the near future, leading to the implementation of a precision-based use of antiepileptic drug (AED) therapy, thereby providing a cornerstone for precision medicine. OBJECTIVE: In this review, we briefly summarize the studies of pharmacogenomics in epilepsy, recent advances, and how it may progress in the future. METHODS: We subdivided the review into two main sections: genetic variants that may modulate response to AEDs through pharmacokinetics or pharmacodynamics mechanisms; and gene variants that may affect tolerability and safety of AEDs...
September 10, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28887371/germline-genetic-variants-with-implications-for-disease-risk-and-therapeutic-outcomes
#15
Amy L Pasternak, Kristen M Ward, Jasmine A Luzum, Vicki L Ellingrod, Daniel L Hertz
Genetic testing has multiple clinical applications including disease risk assessment, diagnosis and pharmacogenomics. Pharmacogenomics can be utilized to predict whether a pharmacologic therapy will be effective or to identify patients at risk for treatment-related toxicity. Although genetic tests are typically ordered for a distinct clinical purpose, the genetic variants that are found may have additional implications for either disease or pharmacology. This review will address multiple examples of germline genetic variants that are informative for both disease and pharmacogenomics...
September 8, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28884473/pharmacotherapy-for-smoking-cessation-effects-by-subgroup-defined-by-genetically-informed-biomarkers
#16
REVIEW
Ewoud Schuit, Orestis A Panagiotou, Marcus R Munafò, Derrick A Bennett, Andrew W Bergen, Sean P David
BACKGROUND: Smoking cessation therapies are not effective for all smokers, and researchers are interested in identifying those subgroups of individuals (e.g. based on genotype) who respond best to specific treatments. OBJECTIVES: To assess whether quit rates vary by genetically informed biomarkers within pharmacotherapy treatment arms and as compared with placebo. To assess the effects of pharmacotherapies for smoking cessation in subgroups of smokers defined by genotype for identified genome-wide significant polymorphisms...
September 8, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28878340/the-pharmacogenomics-of-valproic-acid
#17
REVIEW
Miao-Miao Zhu, Hui-Lan Li, Li-Hong Shi, Xiao-Ping Chen, Jia Luo, Zan-Ling Zhang
Valproic acid is an anticonvulsant and mood-stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder. Adverse effects of valproic acid are rare, but hepatotoxicity is severe in particular in those younger than 2 years old and polytherapy. During valproic acid treatment, it is difficult for prescribers to predict its individual response. Recent advances in the field of pharmacogenomics have indicated variants of candidate genes that affect valproic acid efficacy and safety. In this review, a large number of candidate genes that influence valproic acid pharmacokinetics and pharmacodynamics are discussed, including metabolic enzymes, drug transporters, neurotransmitters and drug targets...
September 7, 2017: Journal of Human Genetics
https://www.readbyqxmd.com/read/28871186/analysis-of-population-specific-pharmacogenomic-variants-using-next-generation-sequencing-data
#18
Eunyong Ahn, Taesung Park
Functional rare variants in drug-related genes are believed to be highly differentiated between ethnic- or racial populations. However, knowledge of population differentiation (PD) of rare single-nucleotide variants (SNVs), remains widely lacking, with the highest fixation indices, (Fst values), from both rare and common variants annotated to specific genes, having only been marginally used to understand PD at the gene level. In this study, we suggest a new, gene-based PD method, PD of Rare and Common variants (PDRC), for analyzing rare variants, as inspired by Generalized Cochran-Mantel-Haenszel (GCMH) statistics, to identify highly population-differentiated drug response-related genes ("pharmacogenes")...
September 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28868359/immune-mediator-pharmacogenomics-tcl1a-snps-and-estrogen-dependent-regulation-of-inflammation
#19
Ming-Fen Ho, Richard M Weinshilboum
This review describes the important functional implications of TCL1A single nucleotide polymorphisms (SNPs) discovered during pharmacogenomic studies of aromatase inhibitor-induced musculoskeletal adverse events that were subsequently shown to influence the expression of cytokines, chemokines, toll-like receptors (TLR), and NF-κB in a SNP and estrogen-dependent fashion. Functional genomic studies of these SNPs led to the discovery of novel mechanisms that may contribute to disease pathophysiology and which may also increase our understanding of pharmacogenomic aspects of regulation of the expression of inflammatory mediators...
August 2017: Journal of Nature and Science
https://www.readbyqxmd.com/read/28867665/pharmacogenomic-variability-of-oral-baclofen-clearance-and-clinical-response-in-children-with-cerebral-palsy
#20
Matthew J McLaughlin, Yang He, Janice Brunstrom-Hernandez, Liu Lin Thio, Bruce C Carleton, Colin J D Ross, Andrea Gaedigk, Andrew Lewandowski, Hongying Dai, William J Jusko, J Steven Leeder
BACKGROUND: Pharmacogenomic variability can contribute to differences in pharmacokinetics and clinical responses. Pediatric patients with cerebral palsy (CP) with genetic variations have not been studied for these potential differences. OBJECTIVE: To determine the genetic sources of variation in oral baclofen clearance and clinical responses. DESIGN: Pharmacogenomic add-on study to determine variability in oral baclofen clearance and clinical responses...
August 31, 2017: PM & R: the Journal of Injury, Function, and Rehabilitation
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