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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/29160302/role-of-cyp24a1-vdr-and-gc-gene-polymorphisms-on-deferasirox-pharmacokinetics-and-clinical-outcomes
#3
S Allegra, J Cusato, S De Francia, A Arduino, F Longo, E Pirro, D Massano, A De Nicolò, A Piga, A D'Avolio
β-Thalassemia patients develop deficiency in vitamin D absorption and liver hydroxylation, resulting in extremely low calcitriol levels. We explored the role of single-nucleotide polymorphisms (SNPs) involved in vitamin D metabolism, transport and activity on deferasirox pharmacokinetics and outcomes (effectiveness trough levels (Ctrough) and the area under the curve (AUC) cutoffs of 20 μg ml(-1) and 360 μg ml(-1) h(-1), respectively; nonresponse AUC limit of 250 μg ml(-1) h(-1)). Ninety-nine β-thalassemic patients were enrolled...
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
#4
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
#5
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/29157489/nmr-based-pharmacometabonomics-a-new-paradigm-for-personalised-or-precision-medicine
#6
REVIEW
Jeremy R Everett
Metabolic profiling by NMR spectroscopy or hyphenated mass spectrometry, known as metabonomics or metabolomics, is an important tool for systems-based approaches in biology and medicine. The experiments are typically done in a diagnostic fashion where changes in metabolite profiles are interpreted as a consequence of an intervention or event; be that a change in diet, the administration of a drug, physical exertion or the onset of a disease. By contrast, pharmacometabonomics takes a prognostic approach to metabolic profiling, in order to predict the effects of drug dosing before it occurs...
November 2017: Progress in Nuclear Magnetic Resonance Spectroscopy
https://www.readbyqxmd.com/read/29151102/the-effect-of-genistein-supplementation-on-vitamin-d-levels-and-bone-turnover-markers-during-the-summer-in-healthy-postmenopausal-women-role-of-genotypes-of-isoflavone-metabolism
#7
María Pérez-Alonso, Laisa-Socorro Briongos, Marta Ruiz-Mambrilla, Eladio A Velasco, Lidia Linares, Luis Cuellar, José-Manuel Olmos, Daniel De Luis, Antonio Dueñas-Laita, José-Luis Pérez-Castrillón
AIMS: The objective of this study was to determine whether vitamin D and genistein supplementation had an additive beneficial effect on levels of vitamin D and bone markers and whether this effect was mediated by genes regulating isoflavone metabolism. MATERIALS AND METHODS: We carried out a prospective study in postmenopausal women randomized to calcium and vitamin D supplementation or calcium, vitamin D, and genistein supplementation. Vitamin D, parathyroid hormone (PTH), cross-linked C-telopeptide (CTX), and procollagen 1 N-terminal (P1NP) were determined by electrochemiluminescence...
November 18, 2017: Journal of Nutrigenetics and Nutrigenomics
https://www.readbyqxmd.com/read/29149126/pharmacogenomics-principles-and-relevance-to-oncology-nursing%C3%A2
#8
Crystal H Dodson
BACKGROUND: Pharmacogenomics is the fastest growing field in precision medicine. Based on current use, oncology encompasses the largest share of the precision medicine market, necessitating that oncology nurses understand the principles of pharmacogenomics and how it affects clinical practice.
. OBJECTIVES: This article will define precision medicine and pharmacogenomics and will provide examples of pharmacogenomic tests, including those associated with tumor markers, and nursing implications...
December 1, 2017: Clinical Journal of Oncology Nursing
https://www.readbyqxmd.com/read/29141462/a-safety-review-of-medications-used-for-labour-induction
#9
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/29140263/access-to-guideline-recommended-pharmacogenomic-tests-for-cancer-treatments-experience-of-providers-and-patients
#10
Ann Chen Wu, Kathleen M Mazor, Rachel Ceccarelli, Stephanie Loomer, Christine Y Lu
Genomic tests are the fastest growing sector in medicine and medical science, yet there remains a dearth of research on access to pharmacogenomic tests and medications. The objective of this study is to explore providers' and patients' experiences and views on test access as well as strategies used for gaining access. We interviewed clinicians who prescribed medications that should be guided by pharmacogenomic testing and patients who received those prescriptions. We organized the themes into the four dimensions suggested by the World Health Organization framework on access to medications and health technologies...
November 15, 2017: Journal of Personalized Medicine
https://www.readbyqxmd.com/read/29135105/impact-of-abcb1-and-cyp2d6-polymorphisms-on-tamoxifen-treatment-outcomes-and-adverse-events-in-breast-cancer-patients
#11
Sona Argalacsova, Ondrej Slanar, Hana Bakhouche, Lubos Pertuzelka
PURPOSE: This study was designed to evaluate the effect of CYP2D6 and ABCB1 polymorphisms and co-medication on the outcomes and adverse events (AEs) of tamoxifen therapy. METHODS: In total, 258 women (187 postmenopausal and 71 premenopausal) with hormone positive breast carcinoma were retrospectively evaluated. CYP2D6 polymorphisms were evaluated with AmpliChip (Roche), and polymorphisms of ATP-binding cassettes B1 (P-glycoprotein) (ABCB1) rs2032582 and rs1045642 with restriction fragment length polymorphisms polymerase chain reaction (RFLP-PCR)...
September 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29123971/concepts-of-genomics-in-kidney-transplantation
#12
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
#13
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
#14
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/29121487/risk-of-cardiac-events-in-long-qt-syndrome-patients-when-taking-antiseizure-medications
#15
David S Auerbach, Yitschak Biton, Bronislava Polonsky, Scott McNitt, Robert A Gross, Robert T Dirksen, Arthur J Moss
Many antiseizure medications (ASMs) affect ion channel function. We investigated whether ASMs alter the risk of cardiac events in patients with corrected QT (QTc) prolongation. The study included people from the Rochester-based Long QT syndrome (LQTS) Registry with baseline QTc prolongation and history of ASM therapy (n = 296). Using multivariate Anderson-Gill models, we assessed the risk of recurrent cardiac events associated with ASM therapy. We stratified by LQTS genotype and predominant mechanism of ASM action (Na(+) channel blocker and gamma-aminobutyric acid modifier...
October 20, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/29111156/genetics-of-human-susceptibility-to-active-and-latent-tuberculosis-present-knowledge-and-future-perspectives
#16
REVIEW
Laurent Abel, Jacques Fellay, David W Haas, Erwin Schurr, Geetha Srikrishna, Michael Urbanowski, Nimisha Chaturvedi, Sudha Srinivasan, Daniel H Johnson, William R Bishai
Tuberculosis is an ancient human disease, estimated to have originated and evolved over thousands of years alongside modern human populations. Despite considerable advances in disease control, tuberculosis remains one of the world's deadliest communicable diseases with 10 million incident cases and 1·8 million deaths in 2015 alone based on the annual WHO report, due to inadequate health service resources in less-developed regions of the world, and exacerbated by the HIV/AIDS pandemic and emergence of multidrug-resistant strains of Mycobacterium tuberculosis...
October 27, 2017: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/29110140/economic-evaluation-of-implementing-a-novel-pharmacogenomic-test-idgenetix-%C3%A2-to-guide-treatment-of-patients-with-depression-and-or-anxiety
#17
Mehdi Najafzadeh, Jorge A Garces, Alejandra Maciel
BACKGROUND: The response to therapeutics varies widely in patients with depression and anxiety, making selection of an optimal treatment choice challenging. IDgenetix(®), a novel pharmacogenomic test, has been shown to improve outcomes by predicting the likelihood of response to different psychotherapeutic medications. OBJECTIVE: The objective of this study was to estimate the cost effectiveness of implementing a novel pharmacogenomic test (IDgenetix(®)) to guide treatment choices in patients with depression and/or anxiety compared with treatment as usual from the US societal perspective...
November 6, 2017: PharmacoEconomics
https://www.readbyqxmd.com/read/29103762/mirna-genetic-variants-as-potential-diagnostic-biomarkers-for-oral-cancer
#18
Divya Tandon, Jayant Dewangan, Sonal Srivastava, Vivek Kumar Garg, Srikanta Kumar Rath
MicroRNAs (miRNAs) comprise a novel class of small, non-coding endogenous RNAs that have a role in the plethora of regulatory activities by directing their target mRNAs for degradation or translational repression. Single nucleotide polymorphisms (SNPs) in miRNA genes can lead to alteration in mRNA expression, resulting in serious consequences. Detection of miRNA-polymorphisms can potentially improve diagnosis, treatment, prognosis in patients and has extreme implications in the fields of pharmacogenomics and personalization of medicine...
October 10, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/29103068/antiplatelet-therapy-for-secondary-prevention-of-vascular-disease-complications
#19
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/29102378/online-extraction-of-antihypertensive-drugs-and-their-metabolites-from-untreated-human-serum-samples-using-restricted-access-carbon-nanotubes-in-a-column-switching-liquid-chromatography-system
#20
Henrique Dipe de Faria, Carolina Tosin Bueno, Jose Eduardo Krieger, Eduardo Moacyr Krieger, Alexandre Costa Pereira, Paulo Caleb Júnior Lima Santos, Eduardo Costa Figueiredo
A novel analytical method was developed to determine 5 antihypertensive drugs of different pharmacological classes (angiotensin-converting enzyme inhibitors, calcium channel blockers, α-2 adrenergic receptor agonists, angiotensin II receptor blockers, and aldosterone receptor antagonists) and some of their metabolites in human serum. The untreated samples were directly analyzed in a column switching system using an extraction column packed with restricted access carbon nanotubes (RACNTs) in an ultra-high performance liquid chromatography coupled to a mass spectrometer (UHPLC-MS/MS)...
October 31, 2017: Journal of Chromatography. A
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