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Sabine Tejpar, Pu Yan, Hubert Piessevaux, Daniel Dietrich, Peter Brauchli, Dirk Klingbiel, Roberto Fiocca, Mauro Delorenzi, Fred Bosman, Arnaud D Roth
PURPOSE: Irinotecan (CPT-11) in combination with 5-fluorouracil (5FU) is widely used in the treatment of colorectal cancer. We assessed potential clinical variables that may predict toxicity and more specifically the role of UGT1A1 polymorphisms associated with irinotecan toxicity. We used data from the PETACC3 trial, which randomised patients in adjuvant setting to 6 months of leucovorin (LV) and 5FU (LV5/FU2) or LV5/FU2 + irinotecan. PATIENTS AND METHODS: Clinical and toxicity data were available for 2982 patients, DNA was available for 1200 (40%) of these patients...
June 14, 2018: European Journal of Cancer
Christine McNamee
No abstract text is available yet for this article.
June 13, 2018: Drug Discovery Today
Chiara Fabbri, Alessandro Serretti
A frustrating inertia has affected the development of clinical applications of antidepressant pharmacogenetics and personalized treatments of depression are still lacking 20 years after the first findings. Candidate gene studies provided replicated findings for some polymorphisms, but each of them shows at best a small effect on antidepressant efficacy and the cumulative effect of different polymorphisms is unclear. Further, no candidate was immune by at least some negative studies. These considerations give rise to some concerns about the clinical benefits of currently available pharmacogenetic tests since they are based on the results of candidate gene studies...
June 12, 2018: Neuroscience Letters
Chitra D Mandyam, Sucharita S Somkuwar, Robert J Oliver, Yoshio Takashima
Addictive drugs effect the brain reward circuitry by altering functional plasticity of neurons governing the circuits. Relapse is an inherent problem in addicted subjects and is associated with neuroplasticity changes in several brain regions including the hippocampus. Recent studies have begun to determine the functional significance of adult neurogenesis in the dentate gyrus of the hippocampus, where new neurons in the granule cell layer are continuously generated to replace dying or diseased cells. One of the many negative consequences of chronic methamphetamine (METH) abuse and METH addiction in rodent and nonhuman primate models is a decrease in neural progenitor cells in the dentate gyrus and reduced neurogenesis in the granule cell layer during METH exposure...
2018: Journal of Experimental Neuroscience
Erik Ingelsson, Mark I McCarthy
Type 2 diabetes mellitus (T2D) and obesity already represent 2 of the most prominent risk factors for cardiovascular disease, and are destined to increase in importance given the global changes in lifestyle. Ten years have passed since the first round of genome-wide association studies for T2D and obesity. During this decade, we have witnessed remarkable developments in human genetics. We have graduated from the despair of candidate gene-based studies that generated few consistently replicated genotype-phenotype associations, to the excitement of an exponential harvest of loci robustly associated with medical outcomes through ever larger genome-wide association study meta-analyses...
June 2018: Circulation. Genomic and precision medicine
T Zúñiga Santamaría, P Yescas Gómez, I Fricke Galindo, M González González, A Ortega Vázquez, M López López
INTRODUCTION: Alzheimer disease (AD) is the most common cause of dementia and is considered one of the main causes of disability and dependence affecting quality of life in elderly people and their families. Current pharmacological treatment includes acetylcholinesterase inhibitors (donepezil, galantamine, rivastigmine) and memantine; however, only one-third of patients respond to treatment. Genetic factors have been shown to play a role in this inter-individual variability in drug response...
June 10, 2018: Neurología: Publicación Oficial de la Sociedad Española de Neurología
J Sidney Ang, Martin N Aloise, Diana Dawes, Maryn G Dempster, Robert Fraser, Andrea Paterson, Paul Stanley, Adriana Suarez-Gonzalez, Martin Dawes, Hagit Katzov-Eckert
OBJECTIVE: A simple, non-invasive sample collection method is key for the integration of pharmacogenetics into clinical practice. The aim of this study was to gain samples for pharmacogenetic testing and evaluate the variation between dry-flocked and sponge-tipped buccal swabs in yield and quality of DNA isolated. RESULTS: Thirty-one participants collected samples using dry-flocked swabs and sponge-tipped swabs. Samples were assessed for DNA yield, quality and genotyping performance on a qPCR OpenArray platform of 28 pharmacogenetic SNPs and a CYP2D6 TaqMan copy number variant...
June 14, 2018: BMC Research Notes
Ingrid Fricke-Galindo, Adrián LLerena, Helgi Jung-Cook, Marisol López-López
Carbamazepine (CBZ) is used for the treatment of epilepsy and other neurological and psychiatric disorders. The occurrence of adverse reactions (ADRs) to CBZ can negatively impact the quality of life of patients, as well as, increase health care costs. Thus, knowledge of CBZ-induced ADRs is important to achieve safer treatment outcomes. Areas covered. This review describes the clinical features, known mechanisms, and clinical management of the main CBZ-induced ADRs. In addition, pharmacogenetic studies focused on ADRs induced by CBZ are cited...
June 14, 2018: Expert Review of Clinical Pharmacology
Venkatesh Pilla Reddy, Barry C Jones, Nicola Colclough, Abhishek Srivastava, Joanne Wilson, Danxi Li
Our recent paper (Jones et al., 2017) demonstrated the ability to predict in vivo clearance of Flavin-containing Monooxygenases (FMO) drug substrates, using in vitro human hepatocyte and human liver microsomal intrinsic clearance (CLint) with standard scaling approaches. In this paper, we apply physiologically based pharmacokinetic (PBPK) modelling & simulation approaches (M&S) to predict the clearance, AUC and Cmax together with the plasma profile of a range of drugs from the original study. The human physiological parameters for FMO, such as enzyme abundance in liver, kidney, gut were derived from in vitro data and clinical pharmacogenetics studies...
June 12, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Diego Scheggia, Rosa Mastrogiacomo, Maddalena Mereu, Sara Sannino, Richard E Straub, Marco Armando, Francesca Managò, Simone Guadagna, Fabrizio Piras, Fengyu Zhang, Joel E Kleinman, Thomas M Hyde, Sanne S Kaalund, Maria Pontillo, Genny Orso, Carlo Caltagirone, Emiliana Borrelli, Maria A De Luca, Stefano Vicari, Daniel R Weinberger, Gianfranco Spalletta, Francesco Papaleo
Antipsychotics are the most widely used medications for the treatment of schizophrenia spectrum disorders. While such drugs generally ameliorate positive symptoms, clinical responses are highly variable in terms of negative symptoms and cognitive impairments. However, predictors of individual responses have been elusive. Here, we report a pharmacogenetic interaction related to a core cognitive dysfunction in patients with schizophrenia. We show that genetic variations reducing dysbindin-1 expression can identify individuals whose executive functions respond better to antipsychotic drugs, both in humans and in mice...
June 11, 2018: Nature Communications
Gino Del Ferraro, Andrea Moreno, Byungjoon Min, Flaviano Morone, Úrsula Pérez-Ramírez, Laura Pérez-Cervera, Lucas C Parra, Andrei Holodny, Santiago Canals, Hernán A Makse
Global integration of information in the brain results from complex interactions of segregated brain networks. Identifying the most influential neuronal populations that efficiently bind these networks is a fundamental problem of systems neuroscience. Here, we apply optimal percolation theory and pharmacogenetic interventions in vivo to predict and subsequently target nodes that are essential for global integration of a memory network in rodents. The theory predicts that integration in the memory network is mediated by a set of low-degree nodes located in the nucleus accumbens...
June 11, 2018: Nature Communications
Neha Merchant, Lakkakula V K S Bhaskar, Saimila Momin, Peela Sujatha, Aramati B M Reddy, Ganji Purnachandra Nagaraju
Lipoxygenases (LOXs) are dioxygenases that catalyze the peroxidation of linoleic acid (LA) or arachidonic acid (AA), in the presence of molecular oxygen. The existence of inflammatory component in the tumor microenvironment intimately links the LOXs to gastrointestinal (GI) cancer progression. Amongst the six-different human LOX-isoforms, 5-LOX is the most vital enzyme for leukotriene (LT) biosynthesis, which is the main inflammation intermediaries. As recent investigations have shown the association of 5-LOX with tumor metastasis, there has also been significant progress in discovering the function of 5-LOX pathway in GI cancer...
July 2018: Critical Reviews in Oncology/hematology
Nebojsa Nick Knezevic, Tatiana Tverdohleb, Ivana Knezevic, Kenneth D Candido
It is estimated that the total annual financial cost for pain management in the U.S. exceeds 100 billion dollars. However, when indirect costs are included, such as functional disability and reduction in working hours, the cost can reach more than 300 billion dollars. In chronic pain patients, the role of pharmacogenetics is determined by genetic effects on various pain types, as well as the genetic effect on drug safety and efficacy. In this review article, we discuss genetic polymorphisms present in different types of chronic pain, such as fibromyalgia, low back pain, migraine, painful peripheral diabetic neuropathy and trigeminal neuralgia...
June 8, 2018: International Journal of Molecular Sciences
Patrick M Zhang, Indra Neil Sarkar
Recent technological advancements in genetic testing and the growing accessibility of public genomic data provide researchers with a unique avenue to approach personalized medicine. This feasibility study examined the potential of direct-to-consumer (DTC) genomic tests (focusing on 23andMe) in research and clinical applications. In particular, we combined population genetics information from the Personal Genome Project with adverse event reports from AEOLUS and pharmacogenetic information from PharmGKB. Primarily, associations between drugs based on co-occurring genetic variations and associations between variants and adverse events were used to assess the potential for leveraging single nucleotide polymorphism information from 23andMe...
2018: AMIA Summits on Translational Science Proceedings
A Bourla, E Chaneac, F Ferreri
No abstract text is available yet for this article.
June 7, 2018: L'Encéphale
Belén Lledo, Joaquín Llácer, Jose A Ortiz, Beatriz Martinez, Ruth Morales, Rafael Bernabeu
The AR (androgen receptor) polymorphism is associated with POR risk. Furthermore, the use of androgens in POR remains controversial. Our data could clarify the effectiveness of androgen pretreatment. AR genotyping could help us to identify patients at risk for POR and POR patients that will be benefited of androgen pretreatment. OBJECTIVE: The aim of this project was to investigate if the AR (androgen receptor) polymorphism could be used to identify patients at risk for POR and that will benefit from androgens pretreatment...
June 4, 2018: European Journal of Obstetrics, Gynecology, and Reproductive Biology
Demetrios G Vavvas, Kent W Small, Carl Awh, Brent W Zanke, Robert J Tibshirani, Rafal Kustra
No abstract text is available yet for this article.
June 7, 2018: Proceedings of the National Academy of Sciences of the United States of America
Kate Traynor
No abstract text is available yet for this article.
June 15, 2018: American Journal of Health-system Pharmacy: AJHP
Kate Traynor
No abstract text is available yet for this article.
June 15, 2018: American Journal of Health-system Pharmacy: AJHP
Liam R Brunham, Steven Baker, Andrew Mammen, G B John Mancini, Robert S Rosenson
Statin therapy reduces cardiovascular events in patients with, or at risk of, atherosclerotic cardiovascular disease. However, statins are underutilized in patients for whom they are indicated and are frequently discontinued. Discontinuation may be the result of the development of statin-associated muscle symptoms (SAMS), which encompass a broad spectrum of clinical phenotypes from myalgia to severe myopathy. As with many adverse drug reactions (ADRs), inter-individual variability in susceptibility to SAMS is due, at least in part, to differences in host genetics...
June 5, 2018: Cardiovascular Research
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