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Siriluk Veerasakul, Paritat Watiktinkorn, Samur Thanoi, Caroline F Dalton, Helene A Fachim, Sutisa Nudmamud-Thanoi, Gavin P Reynolds
AIM: The parvalbumin (PV)-containing subgroup of GABAergic neurons is particularly affected in schizophrenia and animal models of psychosis, including after methamphetamine (METH) administration. We investigated whether METH dependence and METH-induced psychosis may involve an effect on DNA methylation of the PVALB promoter. MATERIALS & METHODS: The methylation of a PVALB promoter sequence was determined in 100 METH-dependent and 102 control subjects using pyrosequencing...
August 24, 2017: Pharmacogenomics
Santi Rello-Varona, Oscar M Tirado
No abstract text is available yet for this article.
August 23, 2017: Pharmacogenomics
Jisce R Puik, Laura L Meijer, Tessa Ys Le Large, Mireia Mato Prado, Adam E Frampton, Geert Kazemier, Elisa Giovannetti
Cholangiocarcinoma (CCA) is a lethal malignancy originating from the biliary tract epithelium. Most patients are diagnosed at an advanced stage. Even after resection with curative intent, prognosis remains poor. Previous studies have reported the evolving role of miRNAs as novel biomarkers in cancer diagnosis, prognostication and chemotherapy response. Various miRNAs, such as miR-21, miR-26, miR-122 and miR-150, have been identified as possible blood-based biomarkers for noninvasive diagnosis of CCA. Moreover, epithelial-mesenchymal transition (EMT)- and angiogenesis-associated miRNAs have been implicated in tumor cell dissemination and are able to determine clinical outcome...
August 23, 2017: Pharmacogenomics
Daniel L Hertz, Jasmine A Luzum, Amy L Pasternak, Kristen M Ward, Hao-Jie Zhu, James M Rae, Vicki L Ellingrod
The University of Michigan College of Pharmacy has made substantial investment in the area of pharmacogenomics to further bolster its activity in pharmacogenomics research, implementation and education. Four tenure-track faculty members have active research programs that focus primarily on the discovery of functional polymorphisms (HJ Zhu), and genetic associations with treatment outcomes in patients with cancer (DL Hertz), cardiovascular disease (JA Luzum) and psychiatric conditions (VL Ellingrod). Recent investments from the University and the College have accelerated the implementation of pharmacogenetics broadly across the institution and in targeted therapeutic areas...
July 26, 2017: Pharmacogenomics
Monir Sadat Haerian, Batoul Sadat Haerian, Saadat Molanaei, Farid Kosari, Shahram Sabeti, Farahnaz Bidari-Zerehpoosh, Ebrahim Abdolali
AIM: This study aims to evaluate the association between the MTRR rs1801394 alone or in interaction with the MTHFR rs1801133 and susceptibility to colorectal cancer (CRC) and its characteristics in Iranian population. Additionally, both a systematic review and meta-analysis were performed to derive a more precise assessment of this association. MATERIALS & METHODS: Genomic DNA of 2332 subjects was genotyped for rs1801394. These data were pooled with 17 eligible studies for meta-analysis...
July 10, 2017: Pharmacogenomics
Sara Rufini, Cinzia Ciccacci, Giuseppe Novelli, Paola Borgiani
Crohn's disease is an inflammatory bowel disease showing a high heterogeneity in phenotype and a strong genetic component. The treatment is complex, due to different severity of clinical parameters and to the fact that therapies only permit to control symptoms and to induce remission for short periods. Moreover, all categories of drugs present a great interindividual variability both in terms of efficacy and side effects appearance. For this reason, the identification of specific genomic biomarkers involved in drugs response will be of great clinical utility in order to foresee drug's efficacy and to prevent adverse reactions, permitting a more personalized therapeutic approach...
July 7, 2017: Pharmacogenomics
Alison L H Quinn, Ina Liko, James C Lee
We describe a 38-year-old African-American female treated with warfarin for acute bilateral pulmonary emboli who is a carrier of two rare CYP2C9 variant alleles, *5 and *6, along with VKORC1 -1639GG and CYP4F2 433Val/Val genotypes. Warfarin was dosed according to the hospital's Personalized Medicine Program recommendations of 5-6 mg/day for the first 6 days, and reduced to 2.5 mg/day starting on day 8 and continued for the following 3 weeks. This case sheds further light on the cumulative clinical impact of the CYP2C9 variant alleles, *5 and *6, on warfarin dose requirements and practical considerations for warfarin genotyping in a racially and ethnically diverse population...
July 7, 2017: Pharmacogenomics
Cynthia Marie-Claire, Clément Jourdaine, Jean-Pierre Lépine, Frank Bellivier, Vanessa Bloch, Florence Vorspan
Current treatments of opioid addiction include primarily maintenance medications such as methadone. Chronic exposure to opiate and/or long-lasting maintenance treatment induce modulations of gene expression in brain and peripheral tissues. There is increasing evidence that epigenetic modifications underlie these modulations. This review summarizes published results on opioid-induced epigenetic changes in animal models and in patients. The epigenetic modifications observed with other drugs of abuse often used by opiate abusers are also outlined...
September 2017: Pharmacogenomics
Nisha Nair, Anthony G Wilson, Anne Barton
Rheumatoid arthritis (RA) is a complex disease affecting approximately 0.5-1% of the population. While there are effective biologic therapies, in up to 40% of patients, disease activity remains inadequately controlled. Therefore, identifying factors that predict, prior to the initiation of therapy, which patients are likely to respond best to which treatment is a research priority and DNA methylation is increasingly being explored as a potential theranostic biomarker. DNA methylation is thought to play a role in RA disease pathogenesis and in mediating the relationship between genetic variants and patient outcomes...
September 2017: Pharmacogenomics
Nabiha Yusuf, Bertha Hidalgo, Marguerite R Irvin, Jin Sha, Degui Zhi, Hemant K Tiwari, Devin Absher, Donna K Arnett, Stella W Aslibekyan
AIM: Fenofibrate, a PPAR-α inhibitor used for treating dyslipidemia, has well-documented anti-inflammatory effects that vary between individuals. While DNA sequence variation explains some of the observed variability in response, epigenetic patterns present another promising avenue of inquiry due to the biological links between the PPAR-α pathway, homocysteine and S-adenosylmethionine - a source of methyl groups for the DNA methylation reaction. HYPOTHESIS: DNA methylation variation at baseline is associated with the inflammatory response to a short-term fenofibrate treatment...
September 2017: Pharmacogenomics
Nathalie K Zgheib
The pharmacogenetics (PGx) laboratory at the Department of Pharmacology and Toxicology at the American University of Beirut Faculty of Medicine was established in October 2007. Several projects on the genetic polymorphisms of drug metabolizing enzymes and transporters with treatment of noncommunicable diseases such as cardiac diseases and cancers are ongoing. We have been applying the 'candidate gene' PGx approach, and recently started using higher throughput analyses. The more recent research projects are geared towards performing more extensive genotyping and including bigger and more representative population samples such as by developing research registries and prospectively following up patients...
September 2017: Pharmacogenomics
Laura Ferrero-Miliani, Ditte Bjerre, Claus Stage, Majbritt Busk Madsen, Gesche Jűrgens, Kim Peder Dalhoff, Henrik Berg Rasmussen
The CES1 gene encodes a hydrolase that metabolizes important drugs. Variants generated by exchange of segments with CES1P1 complicate genotyping of CES1. Using a highly specific procedure we examined DNA samples from 200 Caucasians and identified 46 single nucleotide variants (SNVs) in CES1 and 21 SNVs in CES1A2, a hybrid composed of CES1 and CES1P1. Several of these SNVs were novel. The frequencies of SNVs with a potential functional impact were below 0.02 suggesting limited pharmacogenetic potential for CES1 genotyping...
August 2017: Pharmacogenomics
Sarah Jones
No abstract text is available yet for this article.
August 2017: Pharmacogenomics
Katja Susanne Just, Katharina Luise Schneider, Marlen Schurig, Julia Carolin Stingl, Jürgen Brockmöller
Falls is a frequent type of adverse drug reactions causing significant morbidity and mortality in the elderly. We reviewed, with which drugs the risk of falls is relevant and might depend on genomic variation. Pharmacogenetic variability may contribute to drug-induced falls for instance mediated by impaired drug elimination due to inherited deficiency in enzymes like CYP2C9, CYP2C19 and CYP2D6. The relative role of specific genes and polymorphisms in old age may differ from younger people. Biomarkers for frailty, but also genomic biomarkers might help identifying patients at high risk for drug-induced falls...
August 2017: Pharmacogenomics
María Isidoro-García, Almudena Sánchez-Martín, Asunción García-Sánchez, Catalina Sanz, Belén García-Berrocal, Ignacio Dávila
Heterogeneity defines both the natural history of asthma as well as patient's response to treatment. Pharmacogenomics contribute to understand the genetic basis of drug response and thus to define new therapeutic targets or molecular biomarkers to evaluate treatment effectiveness. This review is initially focused on different genes so far involved in the pharmacological response to asthma treatment. Specific considerations regarding allergic asthma, the pharmacogenetics aspects of polypharmacy and the application of pharmacogenomics in new drugs in asthma will also be addressed...
August 2017: Pharmacogenomics
Xandra García-González, Luis A López-Fernández
No abstract text is available yet for this article.
August 2017: Pharmacogenomics
Weili Wang, Jie Liu, Yijing He, Howard L McLeod
Immune checkpoint blockade, which releases the brake of the immune system to enhance anticancer immune response, stands out in the cancer immunotherapy field due to their remarkable and long-lasting effect. However, the overall response rate for currently approved immune checkpoint inhibitors is only about 10-40%. We have summarized three major components, which are the presence of checkpoints, the immune-activation mechanism and the immune-inhibitory mechanism, containing six factors to describe the cancer-immune interaction dynamically and comprehensively, which shed light on promising biomarkers in immune checkpoint therapy...
August 2017: Pharmacogenomics
Pengcheng Shi, Leisi Zhang, Kai Chen, Zhiwu Jiang, Manman Deng, Jie Zha, Xutao Guo, Peng Li, Bing Xu
AIM: To investigate the combined action of decitabine (DAC) with chidamide (CS055) on acute lymphoblastic leukemia (ALL) cells. MATERIALS & METHODS: ALL cell lines as well as primary cells from 17 ALL patients were subjected to different treatments and thereafter cell counting Kit-8 (CCK-8) assay, flow cytometry and western blot were employed to determine IC50, apoptosis and checkpoint kinase 1 and γH2A.X expression. RESULTS: Low-dose DAC combined with CS055 could effectively kill ALL cells by the reduction of cell viability and induction of apoptosis...
August 2017: Pharmacogenomics
Joost W Geenen, Ekaterina V Baranova, Folkert W Asselbergs, Anthonius de Boer, Rick A Vreman, Colin Na Palmer, Anke H Maitland-van der Zee, Anke M Hövels
AIM: To assess the required characteristics (cost, sensitivity and specificity) of a pharmacogenomic test for being a cost-effective prevention of angiotensin-converting enzyme inhibitors induced angioedema. Furthermore, we assessed the influence of only testing high-risk populations. MATERIALS & METHODS: A decision tree was used. RESULTS: With a willingness-to-pay threshold of €20,000 and €80,000 per quality adjusted life year, a 100% sensitive and specific test may have a maximum cost of €1...
August 2017: Pharmacogenomics
Mrudula S Borse, Olivia M Dong, Melissa J Polasek, Joel F Farley, George A Stouffer, Craig R Lee
AIM: Determine whether using CYP2C19 genotype to optimize antiplatelet therapy selection is cost effective over the initial 30 days and 1-year following percutaneous coronary intervention. MATERIALS & METHODS: A cost-effectiveness analysis compared 30-day and 1-year outcomes and cost across three treatment strategies (universal clopidogrel, universal prasugrel, genotype-guided) in a hypothetical cohort. RESULTS: Base-case scenario results at 30 days indicated that the incremental cost per major cardiovascular or bleeding event avoided for genotype-guided treatment was US$8525 and US$42,198 compared with universal clopidogrel and prasugrel, respectively...
August 2017: Pharmacogenomics
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