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Pharmacogenetics

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https://www.readbyqxmd.com/read/29668112/pharmacogenetic-manipulation-of-the-nucleus-accumbens-alters-binge-like-alcohol-drinking-in-mice
#1
Kush Purohit, Puja K Parekh, Joseph Kern, Ryan W Logan, Zheng Liu, Yanhua Huang, Colleen A McClung, John C Crabbe, Angela R Ozburn
BACKGROUND: Chronic alcohol intake leads to long-lasting changes in reward- and stress-related neuronal circuitry. The nucleus accumbens (NAc) is an integral component of this circuitry. Here, we investigate the effects of DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) on neuronal activity in the NAc and binge-like drinking. METHODS: C57BL/6J mice were stereotaxically injected with AAV2 hSyn-HA hM3Dq, -hM4Di, or -eGFP bilaterally into NAc [core + shell, core or shell]...
April 18, 2018: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/29663595/adult-neurogenesis-affects-motivation-to-obtain-weak-but-not-strong-reward-in-operant-tasks
#2
Rose-Marie Karlsson, Alice S Wang, Anup N Sonti, Heather A Cameron
Decreased motivation to seek rewards is a key feature of mood disorders that correlates with severity and treatment outcome. This anhedonia, or apathy, likely reflects impairment in reward circuitry, but the specific neuronal populations controlling motivation are unclear. Granule neurons generated in the adult hippocampus have been implicated in mood disorders, but are not generally considered as part of reward circuits. We investigated a possible role of these new neurons in motivation to work for food and sucrose rewards in operant conditioning tasks using GFAP-TK pharmacogenetic ablation of adult neurogenesis in both rats and mice...
April 16, 2018: Hippocampus
https://www.readbyqxmd.com/read/29662657/5-nucleotidase-cn-ii-emerges-as-a-new-predictive-biomarker-of-response-to-gemcitabine-platinum-combination-chemotherapy-in-non-small-cell-lung-cancer
#3
Francesca Toffalorio, Mariacarmela Santarpia, Davide Radice, Christopher Adrian Jaramillo, Gianluca Spitaleri, Michela Manzotti, Chiara Catania, Lars Petter Jordheim, Giuseppe Pelosi, Godefridus J Peters, Carmelo Tibaldi, Niccola Funel, Lorenzo Spaggiari, Filippo de Braud, Tommaso De Pas, Elisa Giovannetti
A number of pharmacogenetic studies have been carried out in non-small-cell lung cancer (NSCLC) to identify and characterize genes involved in chemotherapy activity. However, the results obtained so far are controversial and no reliable biomarker is currently used to predict clinical benefit from platinum-based chemotherapy, which represents the cornerstone of treatment of advanced NSCLC. This study investigated the expression levels of ERCC1 and of six genes (RRM1, RRM2, hENT1, dCK, cN-II and CDA) involved in gemcitabine metabolism in locally/advanced NSCLC patients treated with gemcitabine/platinum combination...
March 27, 2018: Oncotarget
https://www.readbyqxmd.com/read/29662106/pharmacogenetics-of-platinum-based-chemotherapy-impact-of-dna-repair-and-folate-metabolism-gene-polymorphisms-on-prognosis-of-non-small-cell-lung-cancer-patients
#4
Cristina Pérez-Ramírez, Marisa Cañadas-Garre, Ahmed Alnatsha, Eduardo Villar, Javier Valdivia-Bautista, María José Faus-Dáder, Miguel Ángel Calleja-Hernández
Chemotherapy based on platinum compounds is the standard treatment for NSCLC patients with EGFR wild type, and is also used as second line in mutated EGFR patients. Nevertheless, this therapy presents poor clinical outcomes. ERCC1, ERCC2, XRCC1, MDM2, MTHFR, MTR, and SLC19A1 gene polymorphisms may contribute to individual variation in response and survival to platinum-based chemotherapy. The aim of this study was to investigate the influence of these polymorphisms on response and survival of NSCLC patients treated with platinum-based chemotherapy...
April 17, 2018: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/29660122/significance-of-pharmacogenomics-in-precision-medicine
#5
EDITORIAL
Ingolf Cascorbi
Precision medicine-a term widely used in modern medicine-emphasizes the goal to overcome still existing limitations of therapeutic interventions by tailoring medical treatments to individual patient characteristics. Pharmacogenetics was one of the first scientific approaches taking molecular biomarkers into consideration of diagnostics and therapeutic decisions. This issue of Clinical Pharmacology & Therapeutics on the significance of pharmacogenomics inprecision medicine discusses the ongoing challenges on different levels...
May 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29659353/-genetic-polymorphisms-of-thiopurine-methyltransferase-and-incidence-of-adverse-events-in-patients-with-medical-indication-of-azathioprine
#6
Manuel A Buhl, Graciela Gómez, María Victoria Collado, Elisabet M Oddo, Marina Khoury, Pablo J Azurmendi, Judith Sarano
Azathioprine is a thiopurine which has a narrow therapeutic index and marked hematological and hepatic toxicity. Thiopurine s-methyltransferase is an enzyme involved in the metabolism of thiopurines. Mutations in the gene that encodes the enzyme may augment the risk of adverse events. For that reason, pharmacogenetic determinations prior to the initiation of therapy can provide useful information for the future therapeutic strategy. Nevertheless, its utility in the local environment is not completely established...
2018: Medicina
https://www.readbyqxmd.com/read/29656138/impdh-pharmacogenetics-in-hematopoietic-cell-transplantation-patients
#7
Jeannine S McCune, Barry Storer, Sushma Thomas, Jožefa McKiernan, Rohan Gupta, Brenda M Sandmaier
We evaluated inosine monophosphate dehydrogenase (IMPDH) 1 and IMPDH2 pharmacogenetics in 247 recipient-donor pairs after nonmyeloablative hematopoietic cell transplant (HCT) recipients. Patients were conditioned with total body irradiation + fludarabine, received grafts from related or unrelated donors (10% HLA mismatch), with post-graft immunosuppression of mycophenolate mofetil (MMF) with a calcineurin inhibitor. Recipient and donor IMPDH genotype (rs11706052, rs2278294, rs2278293) were not associated with day 28 T-cell chimerism, acute graft versus host disease, disease relapse, cytomegalovirus reactivation, non-relapse mortality, or overall survival...
April 12, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29652911/pharmacogenetic-landscape-of-metabolic-syndrome-components-drug-response-in-tunisia-and-comparison-with-worldwide-populations
#8
Haifa Jmel, Lilia Romdhane, Yosra Ben Halima, Meriem Hechmi, Chokri Naouali, Hamza Dallali, Yosr Hamdi, Jingxuan Shan, Abdelmajid Abid, Henda Jamoussi, Sameh Trabelsi, Lotfi Chouchane, Donata Luiselli, Sonia Abdelhak, Rym Kefi
Genetic variation is an important determinant affecting either drug response or susceptibility to adverse drug reactions. Several studies have highlighted the importance of ethnicity in influencing drug response variability that should be considered during drug development. Our objective is to characterize the genetic variability of some pharmacogenes involved in the response to drugs used for the treatment of Metabolic Syndrome (MetS) in Tunisia and to compare our results to the worldwide populations. A set of 135 Tunisians was genotyped using the Affymetrix Chip 6...
2018: PloS One
https://www.readbyqxmd.com/read/29652889/the-rostromedial-tegmental-nucleus-is-essential-for-non-rapid-eye-movement-sleep
#9
Su-Rong Yang, Zhen-Zhen Hu, Yan-Jia Luo, Ya-Nan Zhao, Huan-Xin Sun, Dou Yin, Chen-Yao Wang, Yu-Dong Yan, Dian-Ru Wang, Xiang-Shan Yuan, Chen-Bo Ye, Wei Guo, Wei-Min Qu, Yoan Cherasse, Michael Lazarus, Yu-Qiang Ding, Zhi-Li Huang
The rostromedial tegmental nucleus (RMTg), also called the GABAergic tail of the ventral tegmental area, projects to the midbrain dopaminergic system, dorsal raphe nucleus, locus coeruleus, and other regions. Whether the RMTg is involved in sleep-wake regulation is unknown. In the present study, pharmacogenetic activation of rat RMTg neurons promoted non-rapid eye movement (NREM) sleep with increased slow-wave activity (SWA). Conversely, rats after neurotoxic lesions of 8 or 16 days showed decreased NREM sleep with reduced SWA at lights on, which persisted until after lesions of 25 days...
April 13, 2018: PLoS Biology
https://www.readbyqxmd.com/read/29650277/pharmacogenetics-of-androgen-signaling-in-prostate-cancer-focus-on-castration-resistance-and-predictive-biomarkers-of-response-to-treatment
#10
REVIEW
Marzia Del Re, Stefania Crucitta, Giuliana Restante, Eleonora Rofi, Elena Arrigoni, Elisa Biasco, Andrea Sbrana, Erika Coppi, Luca Galli, Sergio Bracarda, Daniele Santini, Romano Danesi
Tumor heterogeneity strongly affects the molecular mechanisms driving resistance to hormonal therapies in castration-resistant prostate cancer. Since the current use of available treatments can be optimized on the basis of the molecular profile of tumor, the present review focuses on genetic biomarkers in prostate cancer and their application to a personalized treatment.
May 2018: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/29629825/cyp3a-pharmacogenetic-association-with-tacrolimus-pharmacokinetics-differs-based-on-route-of-drug-administration
#11
Amy L Pasternak, Lu Zhang, Daniel L Hertz
Tacrolimus is prescribed to the majority of transplant recipients to prevent graft rejection, and although patients are maintained on oral administration, nonoral routes of administration are frequently used in the initial post-transplant period. CYP3A5 genotype is an established predictor of oral tacrolimus dose requirements, and clinical guideline recommendations exist for CYP3A5-guided dose selection. However, the association between CYP3A5 and nonoral tacrolimus administration is currently poorly understood, and differs from the oral tacrolimus relationship...
April 9, 2018: Pharmacogenomics
https://www.readbyqxmd.com/read/29628449/ethical-guidelines-for-genetic-research-on-alcohol-addiction-and-its-applications
#12
Audrey R Chapman, Adrian Carter, Jonathan M Kaplan, Kylie Morphett, Wayne Hall
Research on the genomic correlates to addiction raises ethical issues in a number of different domains. In this paper, we evaluate the status of genetic research on alcohol dependence as background to addressing the ethical issues raised in conducting research on addiction and the application of that research to the formulation of public policies. We conclude that genetic testing is not yet ready for use in the prediction of alcohol dependence liability. Pharmacogenetic testing for responses to treatments may have more clinical utility, although additional research is required to demonstrate utility and cost-effectiveness...
2018: Kennedy Institute of Ethics Journal
https://www.readbyqxmd.com/read/29626260/clinical-utility-of-pharmacogenetic-testing-in-children-and-adolescents-with-severe-mental-disorders
#13
Hilario Blasco-Fontecilla
This is a retrospective cohort study of 20 children and adolescents to evaluate the clinical utility of a pharmacogenetic decision support tool. Twenty children and adolescents underwent pharmacogenetic testing between June 2014 and May 2017. All children and adolescents were evaluated at Puerta de Hierro University Hospital-Majadahonda (Madrid, Spain). We report the proportion of patients achieving clinical improvement, amelioration of side effects, and changes in number of drugs. Data normality was assessed with the Shapiro-Wilk test, and changes of pre- and post-pharmacogenetic testing were analyzed with the Wilcoxon test for paired samples...
April 6, 2018: Journal of Neural Transmission
https://www.readbyqxmd.com/read/29623639/pharmacogenetics-of-opioid-use-disorder-treatment
#14
Richard C Crist, Toni-Kim Clarke, Wade H Berrettini
Opioid use disorder (OUD) is a significant health problem in the United States and many other countries. A combination of issues, most notably increased prescription of opioid analgesics, has resulted in climbing rates of opioid abuse and overdose over the last decade. This ongoing epidemic has produced a growing population of patients requiring treatment for OUD. Medications such as methadone and buprenorphine have well documented success rates in treating the disorder compared with placebo. However, significant percentages of the population still fail to maintain abstinence or reduce illicit opioid use while using such medications...
April 5, 2018: CNS Drugs
https://www.readbyqxmd.com/read/29623444/polygenic-risk-score-use-in-migraine-research
#15
Mona Ameri Chalmer, Ann-Louise Esserlind, Jes Olesen, Thomas Folkmann Hansen
BACKGROUND: The latest Genome-Wide Association Study identified 38 genetic variants associated with migraine. In this type of studies the significance level is very difficult to achieve (5 × 10- 8 ) due to multiple testing. Thus, the identified variants only explain a small fraction of the genetic risk. It is expected that hundreds of thousands of variants also confer an increased risk but do not reach significance levels. One way to capture this information is by constructing a Polygenic Risk Score...
April 5, 2018: Journal of Headache and Pain
https://www.readbyqxmd.com/read/29622878/the-influence-of-cyp2c9-and-vkorc1-gene-polymorphisms-on-the-response-to-warfarin-in-egyptians
#16
Ahmed M L Bedewy, Salah Showeta, Mostafa Hasan Mostafa, Lamia Saeed Kandil
Warfarin is the most commonly used drug for chronic prevention of thromboembolic events, it also ranks high among drugs that cause serious adverse events. The variability in dose requirements has been attributed to inter-individual differences in medical, personal, and genetic factor. Cytochrome P-450 2C9 is the principle enzyme that terminates the anticoagulant effect of warfarin by catalyzing the conversion of the pharmacologically more potent S-enantiomer to its inactive metabolites. Warfarin exerts its effect by inhibition of vitamin K epoxide reductase...
April 2018: Indian Journal of Hematology & Blood Transfusion
https://www.readbyqxmd.com/read/29622783/genetics-of-male-infertility
#17
REVIEW
Csilla Krausz, Antoni Riera-Escamilla
Male infertility is a multifactorial pathological condition affecting approximately 7% of the male population. The genetic landscape of male infertility is highly complex as semen and testis histological phenotypes are extremely heterogeneous, and at least 2,000 genes are involved in spermatogenesis. The highest frequency of known genetic factors contributing to male infertility (25%) is in azoospermia, but the number of identified genetic anomalies in other semen and aetiological categories is constantly growing...
April 5, 2018: Nature Reviews. Urology
https://www.readbyqxmd.com/read/29622698/value-of-supportive-care-pharmacogenomics-in-oncology-practice
#18
REVIEW
Jai N Patel, Lauren A Wiebe, Henry M Dunnenberger, Howard L McLeod
Genomic medicine provides opportunities to personalize cancer therapy for an individual patient. Although novel targeted therapies prolong survival, most patients with cancer continue to suffer from burdensome symptoms including pain, depression, neuropathy, nausea and vomiting, and infections, which significantly impair quality of life. Suboptimal management of these symptoms can negatively affect response to cancer treatment and overall prognosis. The effect of genetic variation on drug response-otherwise known as pharmacogenomics-is well documented and directly influences an individual patient's response to antiemetics, opioids, neuromodulators, antidepressants, antifungals, and more...
April 5, 2018: Oncologist
https://www.readbyqxmd.com/read/29622583/a-pharmacogenetic-approach-to-the-treatment-of-patients-with-pparg-mutations
#19
Maura Agostini, Erik Schoenmakers, Junaid Beig, Louise Fairall, Istvan Szatmari, Odelia Rajanayagam, Frederick W Muskett, Claire Adams, A David Marais, Stephen O'Rahilly, Robert K Semple, Laszlo Nagy, Amit R Majithia, John W R Schwabe, Dirk J Blom, Rinki Murphy, Krishna Chatterjee, David B Savage
Loss-of-function mutations in PPARG cause familial partial lipodystrophy type 3 (FPLD3) and severe metabolic disease in many cases. Missense mutations in PPARG are present in ∼1:500 people. Whilst mutations are often binarily classified as 'benign' or 'deleterious', prospective functional classification of all missense PPARG variants suggests that their impact is graded. Furthermore, in testing novel mutations with both prototypic 'endogenous' (e.g. prostaglandin J2 (PGJ2)) and synthetic ligands (thiazolidinediones, tyrosine agonists), we observed that synthetic agonists selectively rescue function of some PPARγ mutants...
April 5, 2018: Diabetes
https://www.readbyqxmd.com/read/29621993/cholinergic-receptor-nicotinic-alpha-5-subunit-polymorphisms-are-associated-with-smoking-cessation-success-in-women
#20
Paulo Roberto Xavier Tomaz, Juliana Rocha Santos, Jaqueline Scholz, Tânia Ogawa Abe, Patrícia Viviane Gaya, André Brooking Negrão, José Eduardo Krieger, Alexandre Costa Pereira, Paulo Caleb Júnior Lima Santos
BACKGROUND: The identification of variants in the nicotinic acetylcholine receptor (nAChR) subunit genes associated with smoking phenotypes are increasingly important for prevention and treatment of nicotine dependence. In the context of personalized medicine, the aims of this study were to evaluate whether cholinergic receptor nicotinic alpha 2 (CHRNA2), cholinergic receptor nicotinic alpha 3 (CHRNA3), cholinergic receptor nicotinic alpha 5 (CHRNA5) and cholinergic receptor nicotinic beta 3 (CHRNB3) polymorphisms were associated with nicotine dependence severity, and to investigate possible pharmacogenetics markers of smoking cessation treatment...
April 5, 2018: BMC Medical Genetics
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