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https://www.readbyqxmd.com/read/29163177/assessment-of-pharmacogenomic-panel-assay-for-prediction-of-taxane-toxicities-preliminary-results
#1
Raffaele Di Francia, Luigi Atripaldi, Salvo Di Martino, Carla Fierro, Tommaso Muto, Anna Crispo, Sabrina Rossetti, Gaetano Facchini, Massimiliano Berretta
Backbone: Paclitaxel and docetaxel are the primary taxane anticancer drugs regularly used to treat, breast, gastric, ovarian, head/neck, lung, and genitourinary neoplasm. Suspension of taxane treatments compromising patient benefits is more frequently caused by peripheral neuropathy and allergy, than to tumor progression. Several strategies for preventing toxicity have been investigated so far. Recently, findings on the genetic variants associated with toxicity and resistance to taxane-based chemotherapy have been reported...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29160303/the-pnpla3-i148m-variant-is-associated-with-transaminase-elevations-in-type-2-diabetes-patients-treated-with-basal-insulin-peglispro
#2
S Pillai, S Duvvuru, P Bhatnagar, W Foster, M Farmen, S Shankar, C Harris, E Bastyr, B Hoogwerf, A Haupt
Basal insulin peglispro (BIL) is a novel insulin with hepato-preferential action. In phase 3 trials, BIL showed significantly improved glycemic control but higher levels of transaminases (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)), triglycerides (TGs) and liver fat content (LFC) compared with insulin glargine (GL). As variants in PNPLA3 (I148M) and TM6SF2 (E167K) are associated with nonalcoholic fatty liver disease, we assessed these variants in type 2 diabetes (T2D) patients randomized to receive BIL (n=1822) or GL (n=1270) in three phase 3 trials...
November 21, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/29160301/new-insights-into-the-pharmacogenomics-of-antidepressant-response-from-the-gendep-and-star-d-studies-rare-variant-analysis-and-high-density-imputation
#3
C Fabbri, K E Tansey, R H Perlis, J Hauser, N Henigsberg, W Maier, O Mors, A Placentino, M Rietschel, D Souery, G Breen, C Curtis, L Sang-Hyuk, S Newhouse, H Patel, M Guipponi, N Perroud, G Bondolfi, M O'Donovan, G Lewis, J M Biernacka, R M Weinshilboum, A Farmer, K J Aitchison, I Craig, P McGuffin, R Uher, C M Lewis
Genome-wide association studies have generally failed to identify polymorphisms associated with antidepressant response. Possible reasons include limited coverage of genetic variants that this study tried to address by exome genotyping and dense imputation. A meta-analysis of Genome-Based Therapeutic Drugs for Depression (GENDEP) and Sequenced Treatment Alternatives to Relieve Depression (STAR*D) studies was performed at the single-nucleotide polymorphism (SNP), gene and pathway levels. Coverage of genetic variants was increased compared with previous studies by adding exome genotypes to previously available genome-wide data and using the Haplotype Reference Consortium panel for imputation...
November 21, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/29160300/genome-wide-association-study-identifies-the-common-variants-in-cyp3a4-and-cyp3a5-responsible-for-variation-in-tacrolimus-trough-concentration-in-caucasian-kidney-transplant-recipients
#4
W S Oetting, B Wu, D P Schladt, W Guan, R P Remmel, R B Mannon, A J Matas, A K Israni, P A Jacobson
The immunosuppressant tacrolimus (TAC) is metabolized by both cytochrome P450 3A4 (CYP3A4) and CYP3A5 enzymes. It is common for European Americans (EA) to carry two CYP3A5 loss-of-function (LoF) variants that profoundly reduces TAC metabolism. Despite having two LoF alleles, there is still considerable variability in TAC troughs and identifying additional variants in genes outside of the CYP3A5 gene could provide insight into this variability. We analyzed TAC trough concentrations in 1345 adult EA recipients with two CYP3A5 LoF alleles in a genome-wide association study...
November 21, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/29141462/a-safety-review-of-medications-used-for-labour-induction
#5
Lili Sheibani, Deborah A Wing
Induction of labour is a commonly performed procedure around the world. There are various medications used for induction including those commonly used for cervical ripening (prostaglandins) and oxytocin. The ideal agent is one that decreases the time to achieving delivery without compromising maternal or neonatal safety. The 'optimal safe agent' remains undetermined. Areas covered: This article reviews the safety of currently used induction agents. Prostaglandins and oxytocin have proven to be effective in labour induction, and their profiles will be reviewed in this article...
November 15, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/29123971/concepts-of-genomics-in-kidney-transplantation
#6
William S Oetting, Casey Dorr, Rory P Remmel, Arthur J Matas, Ajay K Israni, Pamala A Jacobson
Purpose of review: Identification of genetic variants to aid in individualized treatment of solid organ allograft recipients would improve graft survival. We will review the current state of knowledge for associations of variants with transplant outcomes. Recent findings: Many studies have yet to exhibit robust and reproducible results, however, pharmacogenomic studies focusing on cytochrome P450 (CYP) enzymes, transporters and HLA variants have shown strong associations with outcomes and have relevance towards drugs used in transplant...
June 2017: Current Transplantation Reports
https://www.readbyqxmd.com/read/29123200/discordancy-partitioning-for-validating-potentially-inconsistent-pharmacogenomic-studies
#7
J Sunil Rao, Hongmei Liu
The Genomics of Drug Sensitivity in Cancer (GDSC) and Cancer Cell Line Encyclopedia (CCLE) are two major studies that can be used to mine for therapeutic biomarkers for cancers of a large variety. Model validation using the two datasets however has proved challenging. Both predictions and signatures do not consistently validate well for models built on one dataset and tested on the other. While the genomic profiling seems consistent, the drug response data is not. Some efforts at harmonizing experimental designs has helped but not entirely removed model validation difficulties...
November 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29123141/new-insight-for-pharmacogenomics-studies-from-the-transcriptional-analysis-of-two-large-scale-cancer-cell-line-panels
#8
Benjamin Sadacca, Anne-Sophie Hamy-Petit, Cécile Laurent, Pierre Gestraud, Hélène Bonsang-Kitzis, Alice Pinheiro, Judith Abecassis, Pierre Neuvial, Fabien Reyal
One of the most challenging problems in the development of new anticancer drugs is the very high attrition rate. The so-called "drug repositioning process" propose to find new therapeutic indications to already approved drugs. For this, new analytic methods are required to optimize the information present in large-scale pharmacogenomics datasets. We analyzed data from the Genomics of Drug Sensitivity in Cancer and Cancer Cell Line Encyclopedia studies. We focused on common cell lines (n = 471), considering the molecular information, and the drug sensitivity for common drugs screened (n = 15)...
November 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29103068/antiplatelet-therapy-for-secondary-prevention-of-vascular-disease-complications
#9
REVIEW
Rahul R Goli, Mayur M Contractor, Ashwin Nathan, Sony Tuteja, Taisei Kobayashi, Jay Giri
PURPOSE OF REVIEW: Platelets are activated upon interaction with injured vascular endothelium to form a primary hemostatic plug. Pathogenic thrombosis driven by platelet aggregation can occur in the setting of vascular disease leading to ischemic events. The use of antiplatelet agents has become a mainstay for prevention of the secondary complications of vascular disease. This review summarizes seminal and recent literature related to this area. RECENT FINDINGS: Aspirin is a cornerstone of antiplatelet therapy for coronary artery disease and cerebrovascular disease for prevention of myocardial infarction, stroke, and vascular death...
November 4, 2017: Current Atherosclerosis Reports
https://www.readbyqxmd.com/read/29099060/clinical-pharmacogenetics-of-cytochrome-p450-associated-drugs-in-children
#10
Ida Aka, Christiana J Bernal, Robert Carroll, Angela Maxwell-Horn, Kazeem A Oshikoya, Sara L Van Driest
Cytochrome P450 (CYP) enzymes are commonly involved in drug metabolism, and genetic variation in the genes encoding CYPs are associated with variable drug response. While genotype-guided therapy has been clinically implemented in adults, these associations are less well established for pediatric patients. In order to understand the frequency of pediatric exposures to drugs with known CYP interactions, we compiled all actionable drug-CYP interactions with a high level of evidence using Clinical Pharmacogenomic Implementation Consortium (CPIC) data and surveyed 10 years of electronic health records (EHR) data for the number of children exposed to CYP-associated drugs...
November 2, 2017: Journal of Personalized Medicine
https://www.readbyqxmd.com/read/29095091/an-assessment-of-the-impact-of-pharmacogenomics-on-health-disparities-a-systematic-literature-review
#11
Antony Martin, Jennifer Downing, Michelle Maden, Nigel Fleeman, Ana Alfirevic, Alan Haycox, Munir Pirmohamed
This review assessed evidence of disparities in benefits of pharmacogenomics related to 'model performance' in subgroups of patients and studies which reported impact on health inequalities. 'Model performance' refers to the ability of algorithms including clinical, environmental and genetic information to guide treatment. A total of 4978 abstracts were screened by one reviewer and 30% (1494) were double screened by a second independent reviewer, after which data extraction was performed. Additional forward and backward citation searching of reference lists was conducted...
November 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/29082853/cancer-gene-profiling-in-non-small-cell-lung-cancers-reveals-activating-mutations-in-jak2-and-jak3-with-therapeutic-implications
#12
Shuyu D Li, Meng Ma, Hui Li, Aneta Waluszko, Tatyana Sidorenko, Eric E Schadt, David Y Zhang, Rong Chen, Fei Ye
BACKGROUND: Next-generation sequencing (NGS) of cancer gene panels are widely applied to enable personalized cancer therapy and to identify novel oncogenic mutations. METHODS: We performed targeted NGS on 932 clinical cases of non-small-cell lung cancers (NSCLCs) using the Ion AmpliSeq™ Cancer Hotspot panel v2 assay. RESULTS: Actionable mutations were identified in 65% of the cases with available targeted therapeutic options, including 26% of the patients with mutations in National Comprehensive Cancer Network (NCCN) guideline genes...
October 30, 2017: Genome Medicine
https://www.readbyqxmd.com/read/29075957/pharmacogenomics-of-the-natriuretic-peptide-system-in-heart-failure
#13
REVIEW
Ahmed Abuzaanona, David Lanfear
PURPOSE OF REVIEW: Heart failure (HF) continues to be a public health burden despite advances in therapy, and the natriuretic peptide (NP) system is clearly of critical importance in this setting, spawning valuable diagnostic and prognostic testing, such as B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP), as well as current and future therapeutics, including recombinant natriuretic peptides (e.g., carperitide, nesiritide) and recently sacubitril, which inhibits the key clearance mechanism for NPs...
December 2017: Current Heart Failure Reports
https://www.readbyqxmd.com/read/29072417/prediction-of-response-to-irinotecan-and-drug-toxicity-based-on-pharmacogenomics-test-a-prospective-case-study-in-advanced-colorectal-cancer
#14
A H Emami, S Sadighi, R Shirkoohi, M A Mohagheghi
Background: FOLFIRI regimen, which is composed of 5-FU, Leucovorin, and Irinotecan, is used in the first-line chemotherapy of metastatic colorectal cancer. Irinotecan life threatening toxicity is partly related to cytotoxic drug metabolite which is primarily inactivated by the UGT1A1 enzyme. The primary aim of the present research was to find the correlation between UGT1A1-genotype and clinical toxicity of irinotecan. Methods: In a prospective study from March 2011 to December 2013, all patients with metastatic colorectal cancer who had been referred to Medical Oncology Department of Iran Cancer Institute were genotyped for UGT1A1*28 before the first cycle of chemotherapy...
October 26, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/29068423/comprehensive-analysis-of-cancer-proteogenome-to-identify-biomarkers-for-the-early-diagnosis-and-prognosis-of-cancer
#15
REVIEW
Hem D Shukla
During the past century, our understanding of cancer diagnosis and treatment has been based on a monogenic approach, and as a consequence our knowledge of the clinical genetic underpinnings of cancer is incomplete. Since the completion of the human genome in 2003, it has steered us into therapeutic target discovery, enabling us to mine the genome using cutting edge proteogenomics tools. A number of novel and promising cancer targets have emerged from the genome project for diagnostics, therapeutics, and prognostic markers, which are being used to monitor response to cancer treatment...
October 25, 2017: Proteomes
https://www.readbyqxmd.com/read/29066719/gene-isoforms-as-expression-based-biomarkers-predictive-of-drug-response-in-vitro
#16
Zhaleh Safikhani, Petr Smirnov, Kelsie L Thu, Jennifer Silvester, Nehme El-Hachem, Rene Quevedo, Mathieu Lupien, Tak W Mak, David Cescon, Benjamin Haibe-Kains
Next-generation sequencing technologies have recently been used in pharmacogenomic studies to characterize large panels of cancer cell lines at the genomic and transcriptomic levels. Among these technologies, RNA-sequencing enable profiling of alternatively spliced transcripts. Given the high frequency of mRNA splicing in cancers, linking this feature to drug response will open new avenues of research in biomarker discovery. To identify robust transcriptomic biomarkers for drug response across studies, we develop a meta-analytical framework combining the pharmacological data from two large-scale drug screening datasets...
October 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/29065900/grcalculator-an-online-tool-for-calculating-and-mining-dose-response-data
#17
Nicholas A Clark, Marc Hafner, Michal Kouril, Elizabeth H Williams, Jeremy L Muhlich, Marcin Pilarczyk, Mario Niepel, Peter K Sorger, Mario Medvedovic
BACKGROUND: Quantifying the response of cell lines to drugs or other perturbagens is the cornerstone of pre-clinical drug development and pharmacogenomics as well as a means to study factors that contribute to sensitivity and resistance. In dividing cells, traditional metrics derived from dose-response curves such as IC 50 , AUC, and E max , are confounded by the number of cell divisions taking place during the assay, which varies widely for biological and experimental reasons. Hafner et al...
October 24, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29061644/comprehensive-pharmacogenomic-profiling-of-malignant-pleural-mesothelioma-identifies-a-subgroup-sensitive-to-fgfr-inhibition
#18
Josine M Quispel-Janssen, Jitendra Badhai, Laurel Schunselaar, Stacey Price, Jonathan S Brammeld, Francesco Iorio, Krishna K Kolluri, Mathew J Garnett, Anton Berns, Paul Baas, Ultan McDermott, Jacques Neefjes, Constantine Alifrangis
PURPOSE: Despite intense research, treatment options for patients with mesothelioma are limited and offer only modest survival advantage. We screened a large panel of compounds in multiple mesothelioma models, and correlated sensitivity with a range of molecular features to detect biomarkers of drug response. EXPERIMENTAL DESIGN: We utilised a high-throughput chemical inhibitor screen in a panel of 889 cancer cell lines, including both immortalised and primary early passage mesothelioma lines, alongside comprehensive molecular characterisation using Illumina whole exome sequencing, copy number analysis and Affymetrix array whole transcriptome profiling...
October 23, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29061162/whole-transcriptome-analysis-of-human-erythropoietic-cells-during-ontogenesis-suggests-a-role-of-vegfa-gene-as-modulator-of-fetal-hemoglobin-and-pharmacogenomic-biomarker-of-treatment-response-to-hydroxyurea-in-%C3%AE-type-hemoglobinopathy-patients
#19
Vasiliki Chondrou, Petros Kolovos, Argyro Sgourou, Alexandra Kourakli, Alexia Pavlidaki, Vlasia Kastrinou, Anne John, Argiris Symeonidis, Bassam R Ali, Adamantia Papachatzopoulou, Theodora Katsila, George P Patrinos
BACKGROUND: Human erythropoiesis is characterized by distinct gene expression profiles at various developmental stages. Previous studies suggest that fetal-to-adult hemoglobin switch is regulated by a complex mechanism, in which many key players still remain unknown. Here, we report our findings from whole transcriptome analysis of erythroid cells, isolated from erythroid tissues at various developmental stages in an effort to identify distinct molecular signatures of each erythroid tissue...
October 23, 2017: Human Genomics
https://www.readbyqxmd.com/read/29052219/pharmacogenomic-discovery-to-function-and-mechanism-breast-cancer-as-a-case-study
#20
Liewei Wang, James Ingle, Richard Weinshilboum
Biomedical research is undergoing rapid change, with the development of a series of analytical omics techniques that are capable of generating Biomedical Big Data. These developments provide an unprecedented opportunity to gain novel insight into disease pathophysiology and mechanisms of drug action and response-but they also present significant challenges. Pharmacogenomics is a discipline within Clinical Pharmacology that has been at the forefront in defining, taking advantage of and dealing with the opportunities and challenges of this aspect of the Post-Genome Project world...
October 20, 2017: Clinical Pharmacology and Therapeutics
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