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https://www.readbyqxmd.com/read/29136336/effect-of-polymorphisms-on-the-pharmacokinetics-pharmacodynamics-and-safety-of-sertraline-in-healthy-volunteers
#1
Miriam Saiz-Rodríguez, Carmen Belmonte, Manuel Román, Dolores Ochoa, Dora Koller, María Talegón, María C Ovejero-Benito, Rosario López-Rodríguez, Teresa Cabaleiro, Francisco Abad-Santos
Sertraline is a selective serotonin reuptake inhibitor (SSRI) widely metabolized in the liver by cytochrome P450 (CYP) enzymes. Besides, it is a P-glycoprotein substrate. Moreover, serotonin transporters and serotonin receptors are involved in its efficacy and safety. The aim of the present study was to evaluate the role of polymorphisms of metabolizing enzymes, transporters and receptors on the pharmacokinetics, pharmacodynamics and tolerability of sertraline in healthy volunteers. Forty-six healthy volunteers (24 men and 22 women) receiving a 100-mg single oral dose of sertraline were genotyped for 17 genetic variants of CYP enzymes (CYP2B6, CYP2C9, CYP2C19, CYP2D6), ATP binding cassette subfamily B member 1 (ABCB1), Solute carrier family 6 member 4 (SLC6A4), 5-Hydroxytryptamine receptor 2A (HTR2A) and 5-Hydroxytryptamine receptor 2C (HTR2C) genes...
November 14, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29135105/impact-of-abcb1-and-cyp2d6-polymorphisms-on-tamoxifen-treatment-outcomes-and-adverse-events-in-breast-cancer-patients
#2
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/29134945/drug-drug-interaction-potential-of-the-hepatitis-b-and-hepatitis-d-virus-entry-inhibitor-myrcludex-b-assessed-in-vitro
#3
Antje Blank, Katrin Meier, Stephan Urban, Walter Emil Haefeli, Johanna Weiss
BACKGROUND: Myrcludex B is a first-in-class virus entry inhibitor for patients with chronic hepatitis B or B/D infections. In patients it will be co-administered with drugs needed for the disease or comorbidities. We aimed to define the risk of drug-drug interactions by characterizing the influence of myrcludex B on relevant drug transporting and metabolizing enzymes in vitro. METHODS: Inhibition of P-glycoprotein (P-gp, ABCB1), breast cancer resistance protein (BCRP/ABCG2), and the organic anion transporting polypeptides 1B1 and 1B3 (OATP1B1/SLCO1B1 and OATP1B3/SLCO1B3) was measured in cells over-expressing the respective transporter using fluorogenic substrates...
November 14, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/29133890/longrange-pcr-based-next-generation-sequencing-in-pharmacokinetics-and-pharmacodynamics-study-of-propofol-among-patients-under-general-anaesthesia
#4
Oliwia Zakerska-Banaszak, Marzena Skrzypczak-Zielinska, Barbara Tamowicz, Adam Mikstacki, Michal Walczak, Michal Prendecki, Jolanta Dorszewska, Agnieszka Pollak, Urszula Lechowicz, Monika Oldak, Kinga Huminska-Lisowska, Marta Molinska-Glura, Marlena Szalata, Ryszard Slomski
The individual response of patients to propofol results from the influence of genetic factors. However, the state of knowledge in this matter still remains insufficient. The aim of our study was to determine genetic predictors of variable pharmacokinetics and pharmacodynamics of propofol within selected 9 genes coding for propofol biotransformation enzymes, receptors and transporters. Our studies are the first extensive pharmaocgenetics research of propofol using high throughput sequencing technology. After the design and optimization of long range PCR-based next-generation sequencing experiment, we screened promoter and coding sequences of all genes analyzed among 87 Polish patients undergoing general anaesthesia with propofol...
November 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29133241/in-silico-comparisons-between-natural-inhibitors-of-abcb1-p-glycoprotein-to-overcome-doxorubicin-resistance-in-the-nci-adr-res-cell-line
#5
Mohamed A Morsy, Azza A K El-Sheikh, Ahmed R N Ibrahim, Mohammed A Khedr, Abdulla Y Al-Taher
To investigate compound-protein binding mode and molecular dynamic simulation of P-glycoprotein (P-gp), in silico studies were performed to compare 12 naturally occurring compounds using two softwares. The net results showed that piperine (PIP) had the best binding affinity. In vitro studies on DOX-resistant NCI/ADR-RES cells, known to express P-gp, showed that, dose-dependently, PIP significantly increased intracellular accumulation of rhodamine-123 and had cytotoxic effects accessed by MTT assay. In addition, PIP at 25 and 50μM significantly potentiated DOX-induced cytotoxicity on the same cell line...
November 10, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29132227/oxidative-stress-in-hiv-infection-and-alcohol-use-role-of-redox-signals-in-modulation-of-lipid-rafts-and-abc-transporters
#6
Samikkannu Thangavel, Carmen T Mulet, Venkata S R Atluri, Marisela Agudelo, Rhonda Rosenberg, Jessy G Devieux, Madhavan P N Nair
AIMS: HIV infection induces oxidative stress and alcohol use accelerates disease progression subsequently causing immune dysfunction. However, HIV and alcohol impact on lipid rafts-mediated immune dysfunction remains unknown. In this study, we investigate the modulation by which oxidative stress induces reactive oxygen species (ROS) affecting redox expression, lipid rafts caveiloin-1, ATP-binding cassette (ABC)-transporters, and transcriptional SREBP gene and protein modification and how these mechanisms are associated with arachidonic acid (AA) metabolites in HIV positive alcohol users, and how they escalate immune dysfunction...
November 13, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29126726/exploration-of-1-2-3-triazole-pyrimidine-hybrids-as-potent-reversal-agents-against-abcb1-mediated-multidrug-resistance
#7
Bo Wang, Bing Zhao, Zhe-Sheng Chen, Lu-Ping Pang, Yuan-Di Zhao, Qian Guo, Xin-Hui Zhang, Ying Liu, Guang-Yao Liu, Hao-Zhang, Xin-Yuan Zhang, Li-Ying Ma, Hong-Min Liu
ABCB1-mediated multidrug resistance (MDR) is a principal obstacle for successful cancer chemotherapy. A series of pyrimidine-based hybrid molecules containing 1,2,3-triazole moiety were evaluated for their reversal activities against MDR. The majority of target compounds displayed moderate to great reversal potency. Among these compounds, compound 25 displayed the most potent reversal activity, about 7-fold more potent than Verapamil (VRP). Further mechanism studies revealed that compound 25 could obviously reverse paclitaxel (PTX) resistance in SW620/AD300 cells by increasing accumulation and extending maintenance of PTX...
October 21, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29122696/es2-enhances-the-efficacy-of-chemotherapeutic-agents-in-abcb1-overexpressing-cancer-cells-in-vitro-and-in-vivo
#8
Yanfen Fang, Juanjuan Sun, Xing Zhong, Rui Hu, Jie Gao, Guanfu Duan, Changge Ji, Lijuan Chen, Wanli Zhang, Chunxiao Miao, Haji Akber Aisa, Xiongwen Zhang
ES2 is a new type of jatrophane diterpenoid ester isolated from the fructus E. sororia, a traditional Uyghur medicine in China. Here we reported the multidrug resistance (MDR) reversal effect of ES2 in vitro and in vivo by modulating the function of ATP-binding cassette subfamily B member 1 (ABCB1). ES2 exhibited low cytotoxicity to ABCB1-overexpressing MDR cells and their parental sensitive cells, but sensitized the MDR cells and ABCB1-transfected HEK293 cells to chemotherapeutic drugs that are ABCB1 substrates...
November 7, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29118354/apolipoprotein-m-mediates-sphingosine-1-phosphate-efflux-from-erythrocytes
#9
Pernille M Christensen, Markus H Bosteen, Stefan Hajny, Lars B Nielsen, Christina Christoffersen
Sphingosine-1-phosphate (S1P) is a bioactive lipid implicated in e.g. angiogenesis, lymphocyte trafficking, and endothelial barrier function. Erythrocytes are a main source of plasma S1P together with platelets and endothelial cells. Apolipoprotein M (apoM) in HDL carries 70% of plasma S1P, whereas 30% is carried by albumin. The current aim was to investigate the role of apoM in export of S1P from human erythrocytes. Erythrocytes exported S1P more efficiently to HDL than to albumin, particularly when apoM was present in HDL...
November 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29113667/abcb1-gene-polymorphisms-and-response-to-chemotherapy-in-breast-cancer-patients-a-meta-analysis
#10
Adela Madrid-Paredes, Marisa Cañadas-Garre, Antonio Sánchez-Pozo, Manuela Expósito-Ruiz, Miguel Ángel Calleja-Hernández
The ABCB1 gene encodes the P-glycoprotein, an efflux pump for some antineoplastic agents which acts as a resistance mechanism to chemotherapy. Three SNPs (C3435T, C1236T and G2677T/A), are the most widely studied in ABCB1. The inconsistent conclusions about the association of these polymorphisms and the response to chemotherapy in breast cancer (BC) patients prompted us to conduct a meta-analysis. A total of nine (770 patients), five (566 patients) and three studies (367 patients) relating the ABCB1 C3435T, C1236T and G2677T/A polymorphisms respectively, were included...
December 2017: Surgical Oncology
https://www.readbyqxmd.com/read/29110840/immunohistochemical-and-genetic-characteristics-of-lung-cancer-mimicking-organizing-pneumonia
#11
Tomohiro Ichikawa, Koichi Saruwatari, Sachiyo Mimaki, Masato Sugano, Keiju Aokage, Motohiro Kojima, Tomoyuki Hishida, Satoshi Fujii, Junji Yoshida, Takeshi Kuwata, Atsushi Ochiai, Kenji Suzuki, Masahiro Tsuboi, Koichi Goto, Katsuya Tsuchihara, Genichiro Ishii
INTRODUCTION: Lung cancer mimicking organizing pneumonia (LCOP) is a novel radiological entity of lung adenocarcinoma that could be misdiagnosed as inflammatory lesions. However, the characteristic biological and genetic features of LCOP are not fully clarified. MATERIALS AND METHODS: We used thin-section CT images to select cases of (LCOP) among surgically resected lung adenocarcinoma patients. We compared the clinicopathological characteristics and the immunophenotypes of LCOP (n=44) and other lepidic-predominant adenocarcinomas (non-LCOP, n=56)...
November 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29104509/antisense-lncrna-foxf1-as1-promotes-migration-and-invasion-of-osteosarcoma-cells-through-the-foxf1-mmp-2-9-pathway
#12
Zhu Kun-Peng, Zhang Chun-Lin, Ma Xiao-Long
Osteosarcoma (OS) is the most common primary malignant bone cancer in children and adolescents. Long non-coding RNAs (lncRNAs) have been shown to play significant role in various cancers, including OS. In a previous study, we have reported that a novel antisense lncRNA FOXF1-AS1, also known as FENDRR, could sensitize doxorubicin-resistance of OS cells through down-regulating ABCB1 and ABCC1. Here in, the critical role of FOXF1-AS1 in regulating OS progression was further investigated. Firstly, we found that FOXF1-AS1 and its antisense transcript FOXF1 expression were positively up-regulated in OS tissues and cell lines and correlated with poor prognosis of OS patients...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/29097275/comparison-of-mechanistic-transport-cycle-models-of-abc-exporters
#13
REVIEW
Dániel Szöllősi, Dania Rose-Sperling, Ute A Hellmich, Thomas Stockner
ABC (ATP binding cassette) transporters, ubiquitous in all kingdoms of life, carry out essential substrate transport reactions across cell membranes. Their transmembrane domains bind and translocate substrates and are connected to a pair of nucleotide binding domains, which bind and hydrolyze ATP to energize import or export of substrates. Over four decades of investigations into ABC transporters have revealed numerous details from atomic-level structural insights to their functional and physiological roles...
October 30, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29091211/influence-of-abcb11-and-hnf4%C3%AE-genes-on-daclatasvir-plasma-concentration-preliminary-pharmacogenetic-data-from-the-kineti-c-study
#14
Jessica Cusato, Amedeo De Nicolò, Lucio Boglione, Fabio Favata, Alessandra Ariaudo, Simone Mornese Pinna, Federica Guido, Valeria Avataneo, Chiara Carcieri, Giuseppe Cariti, Giovanni Di Perri, Antonio D'Avolio
Background: Daclatasvir is an inhibitor of HCV non-structural 5A protein and is a P-glycoprotein substrate. Pharmacogenetics has had a great impact on previous anti-HCV therapies, particularly considering the association of IL-28B polymorphisms with dual therapy outcome. Objectives: We investigated the association between daclatasvir plasma concentrations at 2 weeks and 1 month of therapy and genetic variants (SNPs) in genes encoding transporters and nuclear factors (ABCB1, ABCB11 and HNF4α)...
October 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29090664/pharmacogenetics-of-metabolic-genes-of-anthracyclines-in-acute-myeloid-leukemia
#15
Juan Eduardo Megias-Vericat, David Martinez-Cuadron, Maria Jose Herrero, Salvador F Alino, Jose Luis Poveda, Miguel Angel Sanz, Pau Montesinos
BACKGROUND: Anthracyclines in combination with cytarabine have been the standard therapy for acute myeloid leukemia (AML) for decades with high efficacy. However, the majority of patients will show initial resistance or will relapse after initial complete remission. Genetic variability in genes involved in anthracyclines metabolic pathway could be one of the causes of the interindividual differences in clinical outcomes. METHODS: A systematic review of published studies in AML cohorts was carried out in order to analyze the influence of polymorphisms in genes of anthracycline metabolism on efficacy and toxicity...
November 1, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/29080877/-pharmacogenetic-approaches-to-predicting-the-efficiency-and-safety-of-amlodipine-in-patients-with-arterial-hypertension
#16
D A Sychev, N V Shih, E G Kalle, K A Ryzhikova, T E Morozova
An open, non-comparative, prospective clinical study was conducted to evaluate the antihypertensive efficacy and tolerability of amlodipine, a calcium antagonist, in patients with arterial hypertension (AH) I-II stages, depending on the genotype for the polymorphic marker C3435T of the ABCB1 gene. The study included 100 patients with AH I-II stages, aged from 45 to 58 years. The initial dose of amlodipine was 5 mg, duration of treatment was 12 weeks. General clinical examination methods, office measurement and daily blood pressure monitoring, tolerance evaluation, and genotyping using the ABCB1 polymorphic marker C3435T by the PCR-RFLP method (polymerase chain reaction and restriction fragment length polymorphism) were used...
October 2017: Biomedit︠s︡inskai︠a︡ Khimii︠a︡
https://www.readbyqxmd.com/read/29075133/do-cyp2c19-and-abcb1-gene-polymorphisms-and-low-cyp3a4-isoenzyme-activity-have-an-impact-on-stent-implantation-complications-in-acute-coronary-syndrome-patients
#17
Eric Rytkin, Karin B Mirzaev, Elena A Grishina, Valeriy V Smirnov, Kristina A Ryzhikova, Zhannet A Sozaeva, Michael Iu Giliarov, Denis A Andreev, Dmitriy A Sychev
AIM: The aim of this study was to determine the impact of CYP2C19 and ABCB1 gene polymorphisms and CYP3A4 isoenzyme activity on stent implantation complications among patients with an acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI). PATIENTS AND METHODS: Seventy-six patients (median age 63, range 37-91 years) with an ACS who underwent PCI were screened for CYP2C19 and ABCB1 gene polymorphisms with real-time polymerase chain reaction: CYP2C19*2, CYP2C19*17, and ABCB1 3435...
2017: Pharmacogenomics and Personalized Medicine
https://www.readbyqxmd.com/read/29069754/lncrna-fendrr-sensitizes-doxorubicin-resistance-of-osteosarcoma-cells-through-down-regulating-abcb1-and-abcc1
#18
Zhu Kun-Peng, Ma Xiao-Long, Zhang Chun-Lin
Long noncoding RNAs (LncRNAs) act as crucial regulators in various cancers including osteosarcoma (OS), yet their potential roles and molecular mechanisms in OS chemoresistance remain unclear. In the present study, we investigated the role and potential regulatory mechanism of the most down-regulated expressed lncRNA, FENDRR screened by our previous lncRNA microarray analysis between the paired doxorubicin-resistant and sensitive human osteosarcoma cell lines (MG63/DXR vs MG63). FENDRR expression was down-regulated in the doxorubicin-resistant OS cell lines and tissues and negatively correlated to the poor prognosis of OS patients...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29064386/the-role-of-pxr-genotype-and-transporter-expression-in-the-placental-transport-of-lopinavir-in-mice
#19
Sarabjit S Gahir, Micheline Piquette-Miller
Lopinavir (LPV), an antiretroviral protease inhibitor frequently prescribed in HIV-positive pregnancies, is a substrate of Abcb1 and Abcc2. As differences in placental expression of these transporters were seen in Pregnane X Receptor (PXR) -/- mice, we examined the impact of placental transporter expression and fetal PXR genotype on the fetal accumulation of LPV. PXR +/- dams bearing PXR +/+, PXR +/-, and PXR -/- fetuses were generated by mating PXR +/- female mice with PXR +/- males. On gestational day 17, dams were administered 10 mg/kg LPV (i...
October 24, 2017: Pharmaceutics
https://www.readbyqxmd.com/read/29061787/-epigallocatechin-3-gallate-down-regulates-doxorubicin-induced-overexpression-of-p-glycoprotein-through-the-coordinate-inhibition-of-pi3k-akt-and-mek-erk-signaling-pathways
#20
Hana Satonaka, Kumiki Ishida, Miho Takai, Ryoji Koide, Ryota Shigemasa, Jun Ueyama, Tetsuya Ishikawa, Kazuhiko Hayashi, Hidemi Goto, Shinya Wakusawa
BACKGROUND/AIM: (-)-Epigallocatechin-3-gallate (EGCG) has been indicated to regulate the function of P-glycoprotein (P-gp), which is a drug transporter encoded by the MDR1 (ABCB1) gene. P-gp expression is induced by doxorubicin (DOX). We aimed to clarify the mechanisms and inhibitory effects of EGCG on DOX-induced P-gp expression in HepG2 cells. MATERIALS AND METHODS: Rhodamine 123 (Rho123) was used for P-gp substrate. Western blotting and polymerase chain reactions (PCRs) were conducted using specific antibodies and primer sets...
November 2017: Anticancer Research
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