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Xandra García-González, Luis A López-Fernández
No abstract text is available yet for this article.
July 26, 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...
July 26, 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...
July 26, 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...
July 26, 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...
July 26, 2017: Pharmacogenomics
Tahlita Cm Zuiverloon, Dan Theodorescu
Recent advances in next-generation sequencing techniques have greatly improved our understanding of the genomic alterations in bladder cancer. Cisplatin-based chemotherapy provides a viable treatment option in the neoadjuvant, adjuvant and metastatic setting in a selected group of patients, but chemoresistance is a major problem. The underlying mechanisms of treatment resistance are poorly understood and elucidating these pathways will subsequently lead to improved patient selection, less unnecessary drug-related toxicity, improved patient outcome and decreased healthcare costs...
July 26, 2017: Pharmacogenomics
Maja Matic, Joost Lm Jongen, Laure Elens, Saskia N de Wildt, Dick Tibboel, Peter Ae Sillevis Smitt, Ron Hn van Schaik
AIM: To assess association between genetic variants and opioid requirement in cancer patients. MATERIALS & METHODS: A prospective observational trial of 243 advanced cancer patients with inadequate analgesia treated by the palliative care team was analyzed for ABCB1, ARRB2, COMT, GCH1, IL1RN, KCNJ6, OPRM1, RHBDF2, SCN9A and Stat6 polymorphisms. RESULTS: For patients carrying OPRM1 118AG/GG and COMT 472GG (Val158Val) or these genotypes alone, a significant higher median percentage dose increase was observed (95...
July 26, 2017: Pharmacogenomics
Shirley Siang Ning Tan, Alan Yean Yip Fong, Melissa Mejin, Jerry Gerunsin, Khai Liy Kong, Felicia Yien Yin Chin, Lee Len Tiong, Melissa Siaw Han Lim, Asri Said, Ning Zan Khiew, Chi Yen Voon, Nor Hanim Mohd Amin, Yee Ling Cham, Keng Tat Koh, Yen Yee Oon, Tiong Kiam Ong
BACKGROUND: Patients undergoing elective percutaneous coronary intervention (PCI) with drug-eluting stents (DES) who have impaired clopidogrel response, have a higher risk of subsequent major adverse cardiovascular events (MACE). AIM OF THE STUDY: To establish the relationship between CYP2C19 genotype, clopidogrel responsiveness and 1-year MACE. MATERIALS & METHODS: Aspirin/clopidogrel responses were assessed with Multiplate Analyzer and CYP2C19*2 allele by SpartanRx...
July 26, 2017: Pharmacogenomics
Marta Pellicer, Xandra García-González, María I García, Carolina Blanco, Pilar García-Alfonso, Luis Robles, Cristina Grávalos, Daniel Rueda, Joaquín Martínez, Vanessa Pachón, Federico Longo, Virginia Martínez, Irene Iglesias, Sara Salvador, María Sanjurjo, Luis A López-Fernández
AIM: To identify genetic variants associated with capecitabine toxicity in fluoropyrimidine pathway genes using exome sequencing. PATIENTS & METHODS: Exomes from eight capecitabine-treated patients with severe adverse reactions (grade >2), among a population of 319, were sequenced (Ion Proton). SNPs in genes classified as potentially damaging (Sorting Intolerant from Tolerant and Polymorphism Phenotyping v2) were tested for association with toxicity in a validation cohort of 319 capecitabine-treated patients...
July 26, 2017: Pharmacogenomics
Anabel B Sanchez-Spitman, Dirk-Jan Ar Moes, Hans Gelderblom, Vincent O Dezentjé, Jesse J Swen, Henk-Jan Guchelaar
AIM: CYP2D6*2 is considered fully active, but it has been suggested that it only happens in the presence of rs5758550. This study aims to elucidate the impact of this enhancer. MATERIALS & METHODS: DNA and blood samples from women enrolled in the CYPTAM study (NTR1509) were analyzed. Fourteen CYP2D6*2 carriers without the enhancer were reclassified. The relationship of CYP2D6 phenotypes and drug levels was studied. RESULTS: After correction for the absence of the enhancer, the correlation between CYP2D6 phenotypes and endoxifen did not improve (R(2): 0...
July 26, 2017: Pharmacogenomics
Rodney E Shackelford, Junaid M Ansari, Eric X Wei, Jonathan S Alexander, James Cotelingam
The ALK gene, first identified as an anaplastic large cell lymphoma driver mutation, is dysregulated in nearly 20 different human malignancies, including 3-7% of non-small-cell lung cancers (NSCLC). In NSCLC, ALK commonly fuses with the EML4, forming a constitutively active tyrosine kinase that drives oncogenic progression. Recently, several ALK-inhibiting drugs have been developed that are more effective than standard chemotherapeutic regimens in treating advanced ALK-positive NSCLC. For this reason, molecular diagnostic testing for dysregulated ALK expression is a necessary part of identifying optimal NSCLC treatment options...
July 26, 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
Melanie F Myers, Xue Zhang, Brooke McLaughlin, Diane Kissell, Cassandra L Perry, Matthew Veerkamp, Kejian Zhang, Ingrid A Holm, Cynthia A Prows
AIM: To determine parents' use of their children's CYP2D6 research result. We hypothesized that perceived utility, likelihood of sharing and actual sharing of results would differ between parents with children previously exposed (cases) or unexposed (controls) to opioids. METHODS: We returned results by phone (baseline). We surveyed parents about perceived utility and likelihood of sharing their child's research result at baseline, and actual sharing at 3 and 12 months...
July 26, 2017: Pharmacogenomics
Elodie Gautier-Veyret, Sebastien Bailly, Xavier Fonrose, Julia Tonini, Simon Chevalier, Anne Thiebaut-Bertrand, Françoise Stanke-Labesque
How pharmacogenetics modulates the inhibitory effects of inflammation on voriconazole trough concentration (Cmin) remains unknown. In 29 recipients of allogeneic hematopoietic stem cell transplantation retrospectively studied, both a genetic score (which aggregated CYP2C19 and CYP3A genotypes) and inflammation significantly influenced voriconazole Cmin (n = 260). A trend toward (p = 0.03) a greater impact of inflammation in patients with the highest genetic score (corresponding to ultra-rapid metabolizers) was observed...
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
Susanne B Haga
No abstract text is available yet for this article.
July 7, 2017: Pharmacogenomics
Nianjun Liu, Marguerite R Irvin, Degui Zhi, Amit Patki, T Mark Beasley, Deborah A Nickerson, Charles E Hill, Jinbo Chen, Stephen E Kimmel, Nita A Limdi
AIM: We conducted a genome-wide association study using the Illumina Exome Array to identify coding SNPs that may explain additional warfarin dose variability. PATIENTS & METHODS: Analysis was performed after adjustment for clinical variables and genetic factors known to influence warfarin dose among 1680 warfarin users (838 European-Americans and 842 African-Americans). Replication was performed in an independent sample. RESULTS: We confirmed the influence of known genetic variants on warfarin dose variability...
July 7, 2017: Pharmacogenomics
Houssam Halawi, Michael Camilleri
The diagnosis and management of functional gastrointestinal disorders (FGIDs) remain very challenging. In the era of precision medicine, it is important to individualize the treatment of these conditions by providing targeted and effective therapies while minimizing the risk of medication side effects. By using genetic information that predicts and affects the responses to specific medications, it is anticipated that the science of pharmacogenetics in FGIDs will advance the practice of precision medicine. The pathophysiology of FGIDs is complex, involving the interaction between predisposing genetic and environmental factors...
July 7, 2017: Pharmacogenomics
Lisanne En Manson, Cathelijne H van der Wouden, Jesse J Swen, Henk-Jan Guchelaar
No abstract text is available yet for this article.
July 7, 2017: Pharmacogenomics
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