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Pharmacogenomics drugs metabolism

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https://www.readbyqxmd.com/read/28640195/pharmacogenomic-variants-may-influence-the-urinary-excretion-of-novel-kidney-injury-biomarkers-in-patients-receiving-cisplatin
#1
Cara Chang, Yichun Hu, Susan L Hogan, Nickie Mercke, Madeleine Gomez, Cindy O'Bryant, Daniel W Bowles, Blessy George, Xia Wen, Lauren M Aleksunes, Melanie S Joy
Nephrotoxicity is a dose limiting side effect associated with the use of cisplatin in the treatment of solid tumors. The degree of nephrotoxicity is dictated by the selective accumulation of cisplatin in renal tubule cells due to: (1) uptake by organic cation transporter 2 (OCT2) and copper transporter 1 (CTR1); (2) metabolism by glutathione S-transferases (GSTs) and γ-glutamyltransferase 1 (GGT1); and (3) efflux by multidrug resistance-associated protein 2 (MRP2) and multidrug and toxin extrusion protein 1 (MATE1)...
June 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28607505/predictive-genetic-markers-in-neoadjuvant-chemoradiotherapy-for-locally-advanced-esophageal-cancer-a-long-way-to-go-review-of-the-literature
#2
REVIEW
M Gusella, E Pezzolo, Y Modena, C Barile, D Menon, G Crepaldi, F La Russa, A P Fraccon, F Pasini
The role of genetic molecular markers in neoadjuvant treatment for locally advanced esophageal cancer has been reviewed, focusing strictly on concurrent chemoradiation protocols followed by surgery. Eleven studies evaluated the role of mRNA expression profile; the end point was overall survival (OS) in two studies and different definitions of histological response in nine. Genes reported as significant were involved in cell cycle control (30), apoptosis (7), structural molecules (9), cell metabolism (6) and DNA repair (1)...
June 13, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28526150/pharmacogenomics-in-pain-management
#3
REVIEW
Ramsey Saba, Alan D Kaye, Richard D Urman
There is interpatient variability to analgesic administration. Much can be traced to pharmacogenomics variations between individuals. Certain ethnicities are more prone to reduced function of CYP2D6. Weak opioids are subject to interpatient variation based on their CYP2D6 type. Strong opioids have variations based on their transport and individual metabolism. Several cytochrome enzymes have been found to be involved with ketamine but there is no strong evidence of individual polymorphisms manifesting in clinical outcomes...
June 2017: Anesthesiology Clinics
https://www.readbyqxmd.com/read/28523515/distribution-of-exogenous-and-endogenous-cyp3a-markers-and-related-factors-in-healthy-males-and-females
#4
Jieon Lee, Andrew HyoungJin Kim, SoJeong Yi, SeungHwan Lee, Seo Hyun Yoon, Kyung-Sang Yu, In-Jin Jang, Joo-Youn Cho
Cytochrome P450 (CYP) 3A is an important drug-metabolizing enzyme in humans. Assessing CYP3A activity is necessary for predicting therapeutic outcomes or the potential adverse events of various therapeutics. This study sought to evaluate the distribution of endogenous and exogenous markers reflecting hepatic CYP3A activity and related factors affecting its activity in healthy male and female. Each subject was given a single 1 mg dose of midazolam intravenously. Pharmacokinetics, pharmacometabolomics, and pharmacogenomics analyses were performed to evaluate CYP3A activity...
July 2017: AAPS Journal
https://www.readbyqxmd.com/read/28440341/quantitative-profiling-of-the-ugt-transcriptome-in-human-drug-metabolizing-tissues
#5
A Tourancheau, M Rouleau, S Guauque-Olarte, L Villeneuve, I Gilbert, A Droit, C Guillemette
Alternative splicing as a mean to control gene expression and diversify function is suspected to considerably influence drug response and clearance. We report the quantitative expression profiles of the human UGT genes including alternatively spliced variants not previously annotated established by deep RNA-sequencing in tissues of pharmacological importance. We reveal a comprehensive quantification of the alternative UGT transcriptome that differ across tissues and among individuals. Alternative transcripts that comprise novel in-frame sequences associated or not with truncations of the 5'- and/or 3'- termini, significantly contribute to the total expression levels of each UGT1 and UGT2 gene averaging 21% in normal tissues, with expression of UGT2 variants surpassing those of UGT1...
April 25, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28418012/cyp3a4-is-a-crosslink-between-vitamin-d-and-calcineurin-inhibitors-in-solid-organ-transplant-recipients-implications-for-bone-health
#6
REVIEW
A Prytuła, K Cransberg, A Raes
The use of calcineurin inhibitors (CNIs) and vitamin D deficiency may contribute to the pathogenesis of post-transplant bone disease. CNIs and 1,25-dihydroxyvitamin D₃ (1,25(OH)2D3) are substrates of the drug-metabolizing enzyme CYP3A4. This review summarizes the indications for the use of activated vitamin D analogs in post-transplant care and the current knowledge on the impact of CNIs on bone. We searched for clinical evidence of the interaction between CNIs and 1,25(OH)2D3. We also provide an overview of the literature on the interplay between vitamin D metabolism and CYP3A4 in experimental and clinical settings and discuss its possible implications for solid organ transplant recipients...
April 18, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28398354/global-genetic-variation-of-select-opiate-metabolism-genes-in-self-reported-healthy-individuals
#7
F R Wendt, G Pathak, A Sajantila, R Chakraborty, B Budowle
CYP2D6 is a key pharmacogene encoding an enzyme impacting poor, intermediate, extensive and ultrarapid phase I metabolism of many marketed drugs. The pharmacogenetics of opiate drug metabolism is particularly interesting due to the relatively high incidence of addiction and overdose. Recently, trans-acting opiate metabolism and analgesic response enzymes (UGT2B7, ABCB1, OPRM1 and COMT) have been incorporated into pharmacogenetic studies to generate more comprehensive metabolic profiles of patients. With use of massively parallel sequencing, it is possible to identify additional polymorphisms that fine tune, or redefine, previous pharmacogenetic findings, which typically rely on targeted approaches...
April 11, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28377107/vitamin-pharmacogenomics-new-insight-into-individual-differences-in-diseases-and-drug-responses
#8
REVIEW
Hai-Yan He, Mou-Ze Liu, Yue-Li Zhang, Wei Zhang
Vitamins are vital to sustain normal physiological function, metabolism, and growth for all living organisms. Being an integral component of coenzyme, vitamins can affect the catalytic activities of many enzymes and the expression of drug transporters. Genetic variations in metabolism and/or transporter genes of drugs can influence the exposure of the human body to drugs and/or their active metabolites, thus contributing to the variations in drug responses and toxicities. Nonetheless, pharmacogenomics studies on nutrients have been rarely summarized...
April 2017: Genomics, Proteomics & Bioinformatics
https://www.readbyqxmd.com/read/28368577/classics-in-chemical-neuroscience-aripiprazole
#9
Austen B Casey, Clinton E Canal
Aripiprazole was the first antipsychotic developed to possess agonist properties at dopamine D2 autoreceptors, a groundbreaking strategy that presented a new vista for schizophrenia drug discovery. The dopamine D2 receptor is the crucial target of all extant antipsychotics, and all developed prior to aripiprazole were D2 receptor antagonists. Extensive blockade of these receptors, however, typically produces extrapyramidal (movement) side effects, which plagued first-generation antipsychotics, such as haloperidol...
June 21, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28361099/a-de-novo-splice-site-mutation-in-ehmt1-resulting-in-kleefstra-syndrome-with-pharmacogenomics-screening-and-behavior-therapy-for-regressive-behaviors
#10
Amit Kumar Mitra, Jessica Dodge, Jody Van Ness, Israel Sokeye, Brian Van Ness
BACKGROUND: Kleefstra syndrome (KS) is a rare autosomal dominant developmental disability, caused by microdeletions or intragenic mutations within the epigenetic regulator gene EHMT1 (euchromatic histone lysine N-methyltransferase 1). In addition to common features of autism, young adult regressive behaviors have been reported. However, the genetic downstream effects of the reported deletions or mutations on KS phenotype have not yet been completely explored. While genetic backgrounds affecting drug metabolism can have a profound effect on therapeutic interventions, pharmacogenomic variations are seldom considered in directing psychotropic therapies...
March 2017: Molecular Genetics & Genomic Medicine
https://www.readbyqxmd.com/read/28345177/pharmacogenomics-of-off-target-adverse-drug-reactions
#11
REVIEW
Sarah L Garon, Rebecca K Pavlos, Katie D White, Nancy J Brown, Cosby A Stone, Elizabeth J Phillips
Off-target adverse drug reactions (ADRs) are associated with significant morbidity and costs to the healthcare system, and their occurrence is not predictable based on the known pharmacological action of the drug's therapeutic effect. Off-target ADRs may or may not be associated with immunological memory, although they can manifest with a variety of shared clinical features, including maculopapular exanthema, severe cutaneous adverse reactions (SCARs), angioedema, pruritus and bronchospasm. Discovery of specific genes associated with a particular ADR phenotype is a foundational component of clinical translation into screening programmes for their prevention...
March 26, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28343093/influence-of-genetic-variants-of-cyp2d6-cyp2c9-cyp2c19-and-cyp3a4-on-antiepileptic-drug-metabolism-in-pediatric-patients-with-refractory-epilepsy
#12
Miguel A López-García, Iris A Feria-Romero, Héctor Serrano, Darío Rayo-Mares, Pietro Fagiolino, Marta Vázquez, Consuelo Escamilla-Núñez, Israel Grijalva, David Escalante-Santiago, Sandra Orozco-Suarez
BACKGROUND: Identified the polymorphisms of CYP2D6, CYP2C9, CYP2C19 and CYP3A4, within a rigorously selected population of pediatric patients with drug-resistant epilepsy. METHOD: The genomic DNA of 23 drug-resistant epilepsy patients and 7 patients with good responses were analyzed. Ten exons in these four genes were genotyped, and the drug concentrations in saliva and plasma were determined. RESULTS: The relevant SNPs with pharmacogenomics relations were CYP2D6*2 (rs16947) decreased your activity and CYP2D6*4 (rs1065852), CYP2C19*2 (rs4244285) and CYP3A4*1B (rs2740574) by association with poor metabolizer...
June 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28322157/diabetes-related-neurological-implications-and-pharmacogenomics
#13
Rojas Carranza Camilo Andrés, Bustos Cruz Rosa Helena, Pino Pinzón Carmen Juliana, Ariza Marquez Yeimy Viviana, Gómez Bello Rosa Margarita, Cañadas Garre Marisa
Diabetes mellitus (DM) is the most commonly occurring cause of neuropathy around the world and is beginning to grow in countries where there is a risk of obesity. DM Type II, (T2DM) is a common age-related disease and is a major health concern, particularly in developed countries in Europe where the population is aging. T2DM is a chronic disease which is characterised by hyperglycemia, hyperinsulinemia and insulin resistance, together with the body's inability to use glucose as energy. Such metabolic disorder produces a chronic inflammatory state, as well as changes in lipid metabolism leading to hypertriglyceridemia, thereby producing chronic deterioration of the organs and premature morbidity and mortality...
March 17, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28315483/functional-proteomic-analysis-of-corticosteroid-pharmacodynamics-in-rat-liver-relationship-to-hepatic-stress-signaling-energy-regulation-and-drug-metabolism
#14
Vivaswath S Ayyar, Richard R Almon, Debra C DuBois, Siddharth Sukumaran, Jun Qu, William J Jusko
Corticosteroids (CS) are anti-inflammatory agents that cause extensive pharmacogenomic and proteomic changes in multiple tissues. An understanding of the proteome-wide effects of CS in liver and its relationships to altered hepatic and systemic physiology remains incomplete. Here, we report the application of a functional pharmacoproteomic approach to gain integrated insight into the complex nature of CS responses in liver in vivo. An in-depth functional analysis was performed using rich pharmacodynamic (temporal-based) proteomic data measured over 66h in rat liver following a single dose of methylprednisolone (MPL)...
May 8, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28296649/a-nomogram-to-predict-5-fluorouracil-toxicity-when-pharmacogenomics-meets-the-patient
#15
Andrea Botticelli, Concetta E Onesti, Lidia Strigari, Mario Occhipinti, Francesca R Di Pietro, Bruna Cerbelli, Antonella Petremolo, Elisabetta Anselmi, Serena Macrini, Michela Roberto, Rosa Falcone, Luana Lionetto, Marina Borro, Annalisa Milano, Giovanna Gentile, Maurizio Simmaco, Paolo Marchetti, Federica Mazzuca
Fluoropyrimidines combined with other agents are commonly used for gastrointestinal cancer treatment. Considering that severe toxicities occur in 30% of patients, we aimed to structure a nomogram to predict toxicity, based on metabolic parameter and patients' characteristics. We retrospectively enrolled patients affected by gastrointestinal tract cancers. Pretreatment 5-fluorouracil (5-FU) degradation rate and DPYD, TSER, MTHFR A1298T, and C677T gene polymorphisms were characterized. Data on toxicities were collected according to CTCAE v3...
June 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28295240/pharmacogenomic-advances-in-the-prediction-and-prevention-of-cutaneous-idiosyncratic-drug-reactions
#16
R-Y Pan, R-L Dao, S-I Hung, W-H Chung
Cutaneous idiosyncratic drug reactions (CIDRs) are usually unpredictable, ranging from mild maculopapular exanthema (MPE) to severe cutaneous adverse drug reactions (SCARs) such as drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). Increasing evidence suggests that HLA alleles are strongly associated with drug-induced-CIDRs. The pathomechanisms for CIDRs include genetic polymorphisms affecting complex immune-specific HLA/drug antigen/T-cell receptor interactions and drug metabolism...
March 15, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28271978/lessons-from-cuba-for-global-precision-medicine-cyp2d6-genotype-is-not-a-robust-predictor-of-cyp2d6-ultrarapid-metabolism
#17
Pedro Dorado, Idilio González, María Eugenia G Naranjo, Fernando de Andrés, Eva María Peñas-Lledó, Luis Ramón Calzadilla, Adrián LLerena
A long-standing question and dilemma in precision medicine is whether and to what extent genotyping or phenotyping drug metabolizing enzymes such as CYP2D6 can be used in real-life global clinical and societal settings. Although in an ideal world using both genotype and phenotype biomarkers are desirable, this is not always feasible for economic and practical reasons. Moreover, an additional barrier for clinical implementation of precision medicine is the lack of correlation between genotype and phenotype, considering that most of the current methods include only genotyping...
January 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28257284/pharmacogenomics-and-tailored-polypharmacy-an-80-year-old-lady-with-rosuvastatin-associated-rhabdomyolysis-and-maprotiline-related-ogilvie-s-syndrome%C3%A2
#18
Katherina B Sreter, Blazenka Barisic, Sanja Popovic-Grle
What is known and objectives: Multiple adverse drug reactions (ADRs) are expected, and thus should be prevented in the elderly comorbid patient on polypharmacy. Rosuvastatin is commonly prescribed for the treatment and prevention of atherosclerotic diseases, and in rare cases, is associated with rhabdomyolysis. Maprotiline is a tetracyclic antidepressant, infrequently used in the United States, but seemingly more broadly in European countries. Acute colonic pseudo-obstruction (Ogilvie's syndrome) caused by maprotiline has thus far, to our knowledge, not yet been described in the literature...
May 2017: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28210221/pharmacogenomic-characterization-and-isobologram-analysis-of-the-combination-of-ascorbic-acid-and-curcumin-two-main-metabolites-of-curcuma-longa-in-cancer-cells
#19
Edna Ooko, Onat Kadioglu, Henry J Greten, Thomas Efferth
Curcuma longa has long been used in China and India as anti-inflammatory agent to treat a wide variety of conditions and also as a spice for varied curry preparations. The chemoprofile of the Curcuma species exhibits the presence of varied phytochemicals with curcumin being present in all three species but AA only being shown in C. longa. This study explored the effect of a curcumin/AA combination on human cancer cell lines. The curcumin/AA combination was assessed by isobologram analysis using the Loewe additivity drug interaction model...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28176639/personalized-medicine-in-the-paediatric-population-the-balance-between-pharmacogenetics-progress-and-bioethics
#20
Stefania Schiavone, Margherita Neri, Cristoforo Pomara, Irene Riezzo, Luigia Trabace, Emanuela Turillazzi
Personalized medicine (PM) is becoming increasingly important in contemporary clinical and research scenarios. In the context of PM, pharmacogenomics and pharmacogenetics are aimed at the genetic personalization of drug response. Extrinsic and intrinsic factors may explain inter-individual variability in drug response. Among such factors, age seems to specifically intervene to modulate drug response since normal developmental changes may influence the exposure-response relation. Consequently, the potential benefit of pharmacogenomics (PGx) in the paediatric population is considerable...
February 7, 2017: Current Pharmaceutical Biotechnology
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