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https://www.readbyqxmd.com/read/28208135/abcb1-and-slco1b3-gene-polymorphisms-and-their-impact-on-digoxin-pharmacokinetics-in-atrial-fibrillation-patients-among-the-tunisian-population
#1
Nejia Tounsi, Imen Trabelsi, Emna Kerkeni, Mohamed Habib Grissa, Nizar Fredj, Adel Sekma, Malek Mzali, Ilhem Hellara, Kamel Monastiri, Wahiba Douki, Semir Nouira
BACKGROUND: Digoxin is a substrate of P-glycoprotein (P-gp) and organic anion transporting polypeptide transporters that are encoded by ABCB1 and SLCO1B3 genes. Genetic polymorphisms in both genes may explain inter-individual variability of serum digoxin concentration (SDC). This study evaluates the possible effect of the most common ABCB1 and SLCO1B3 polymorphisms on SDC after a single oral dose of digoxin in Tunisian atrial fibrillation (AF) patients. METHODS: ABCB1 and SLCO1B3 genotypes were analyzed in 102 patients with AF who received digoxin (0...
February 17, 2017: Pharmacology
https://www.readbyqxmd.com/read/28207188/polymorphism-in-the-abcb1-gene-is-associated-with-the-risk-of-bullous-pemphigoid-in-a-polish-population
#2
Mariola Rychlik-Sych, Małgorzata Barańska, Michał Dudarewicz, Jadwiga Skrętkowicz, Agnieszka Żebrowska, Jacek Owczarek, Elżbieta Waszczykowska
BACKGROUND AND OBJECTIVES: Polymorphisms in the P-glycoprotein-encoding ABCB1 gene may affect the intracellular concentration of xenobiotics, and thus contribute to the development of autoimmune diseases, including bullous pemphigoid (BP). The objective of the present study was to investigate whether there is an association between the C3435T and G2677T/A polymorphisms in the ABCB1 gene and the risk of BP in a Polish population. PATIENTS AND METHODS: The study included 71 patients with BP and 156 healthy volunteers...
February 16, 2017: Journal der Deutschen Dermatologischen Gesellschaft, Journal of the German Society of Dermatology: JDDG
https://www.readbyqxmd.com/read/28202008/relationship-between-abcb1-3435tt-genotype-and-antiepileptic-drugs-resistance-in-epilepsy-updated-systematic-review-and-meta-analysis
#3
Malek Chouchi, Wajih Kaabachi, Hedia Klaa, Kalthoum Tizaoui, Ilhem Ben-Youssef Turki, Lamia Hila
BACKGROUND: Antiepileptic drugs (AEDs) are effective medications available for epilepsy. However, many patients do not respond to this treatment and become resistant. Genetic polymorphisms may be involved in the variation of AEDs response. Therefore, we conducted an updated systematic review and a meta-analysis to investigate the contribution of the genetic profile on epilepsy drug resistance. METHODS: We proceeded to the selection of eligible studies related to the associations of polymorphisms with resistance to AEDs therapy in epilepsy, published from January 1980 until November 2016, using Pubmed and Cochrane Library databases...
February 15, 2017: BMC Neurology
https://www.readbyqxmd.com/read/28194153/nasal-polyp-derived-mesenchymal-stromal-cells-exhibit-lack-of-immune-associated-molecules-and-high-levels-of-stem-progenitor-cells-markers
#4
Pedro Wey Barbosa de Oliveira, Rogério Pezato, Juan Sebastian Henao Agudelo, Claudina Angela Perez-Novo, Wim Vanden Berghe, Niels Olsen Câmara, Danilo Candido de Almeida, Luís Carlos Gregorio
Mesenchymal stromal cells (MSCs) are considered adult progenitor stem cells and have been studied in a multitude of tissues. In this context, the microenvironment of nasal polyp tissue has several inflammatory cells, but their stroma compartment remains little elucidated. Hence, we isolated MSCs from nasal polyps Polyp-MSCs (PO-MSCs) and compared their molecular features and gene expression pattern with bone marrow-derived MSCs (BM-MSCs). Initially, both PO-MSCs and BM-MSCs were isolated, cultivated, and submitted to morphologic, differentiation, phenotypic, immunosuppressive, and gene expression assays...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28188910/expression-and-splicing-of-abc-and-slc-transporters-in-the-human-blood-brain-barrier-measured-with-rnaseq
#5
Adam M Suhy, Amy Webb, Audrey C Papp, Ethan G Geier, Wolfgang Sadee
The blood-brain barrier (BBB) expresses numerous membrane transporters that supply needed nutrients to the central nervous system (CNS), consisting mostly of solute carriers (SLC transporters), or remove unwanted substrates via extrusion pumps through the action of ATP binding cassette (ABC) transporters. Previous work has identified many BBB transporters using hybridization arrays or qRT-PCR, using targeted probes. Here we have performed next-generation sequencing of the transcriptome (RNAseq) extracted from cerebral cortex tissues and brain microvessel endothelial cells (BMEC) obtained from two donors...
February 7, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28181548/thiazole-valine-peptidomimetic-ttt-28-antagonizes-multidrug-resistance-in-vitro-and-in-vivo-by-selectively-inhibiting-the-efflux-activity-of-abcb1
#6
Yi-Jun Wang, Bhargav A Patel, Nagaraju Anreddy, Yun-Kai Zhang, Guan-Nan Zhang, Saeed Alqahtani, Satyakam Singh, Suneet Shukla, Amal Kaddoumi, Suresh V Ambudkar, Tanaji T Talele, Zhe-Sheng Chen
Multidrug resistance (MDR) attenuates the chemotherapy efficacy and increases the probability of cancer recurrence. The accelerated drug efflux mediated by ATP-binding cassette (ABC) transporters is one of the major MDR mechanisms. This study investigated if TTT-28, a newly synthesized thiazole-valine peptidomimetic, could reverse ABCB1-mediated MDR in vitro and in vivo. TTT-28 reversed the ABCB1-mediated MDR and increased the accumulation of [(3)H]-paclitaxel in ABCB1 overexpressing cells by selectively blocking the efflux function of ABCB1, but not interfering with the expression level and localization of ABCB1...
February 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28179302/cd24-modulates-chemosensitivity-of-mcf-7-breast-cancer-cells
#7
Hideya Onishi, Kumi Suyama, Akio Yamasaki, Yasuhiro Oyama, Akiko Fujimura, Makoto Kawamoto, Akira Imaizumi
The role of cluster of differentiation (CD) 24 in breast cancer remains unclear; previously, we showed that CD24 suppresses malignant phenotypes by inactivating Hedgehog signaling through signal transducer and activator of transcription (STAT) 1 inhibition. In this study, we examined how CD24 affects chemosensitivity in breast cancer cells. The CD44(+)CD24(+) breast cancer cell line MCF-7 was transfected with CD24 with/without STAT1 siRNA, and chemosensitivity to 5-fluorouracil (5-FU) and cis-diamminedichloroplatinum (CDDP) was measured...
2017: Anticancer Research
https://www.readbyqxmd.com/read/28178648/polymorphisms-of-esr1-ugt1a1-hcn1-map3k1-and-cyp2b6-are-associated-with-the-prognosis-of-hormone-receptor-positive-early-breast-cancer
#8
Sung-Hsin Kuo, Shi-Yi Yang, San-Lin You, Huang-Chun Lien, Ching-Hung Lin, Po-Han Lin, Chiun-Sheng Huang
In this study, we investigated whether single nucleotide polymorphisms (SNPs) identified by genome-wide association study (GWAS) (MAP3K1, FGFR2, TNRC9, HCN1, and 5p12), and SNPs involved in the metabolism of estrogen (CYP19, COMT, ESR1, and UGT1A1), tamoxifen (CYP2C9, CYP2C19, CYP3A5, and CYP2D6), and chemotherapeutic agents (ABCB1, ALDH3A1, and CYP2B6) are associated with the prognoses of 414 hormone receptor (HR)-positive early breast cancers with negative or 1 to 3 nodal metastases. At a median follow-up period of 10...
February 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28165634/pharmacogenetics-of-antiepileptic-drug-efficacy-in-childhood-absence-epilepsy
#9
Tracy A Glauser, Katherine Holland, Valerie P O'Brien, Mehdi Keddache, Lisa J Martin, Peggy O Clark, Avital Cnaan, Dennis Dlugos, Deborah G Hirtz, Shlomo Shinnar, Gregory Grabowski
OBJECTIVE: Determine if common polymorphisms in CACNA1G, CACNA1H, CACNA1I, and ABCB1 are associated with differential short term seizure outcome in Childhood Absence Epilepsy (CAE). METHODS: 446 CAE children in a randomized double blind trial of ethosuximide, lamotrigine and valproate had short term seizure outcome determined. Associations between polymorphisms (minor allele frequency ≥15%) in four genes and seizure outcomes were assessed. In vitro electrophysiology on transfected CACNA1H channels determined impact of one variant on T-type calcium channel responsiveness to ethosuximide...
February 6, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28164520/the-effect-of-abcb1-polymorphisms-on-serial-tacrolimus-concentrations-in-stable-austrian-long-term-kidney-transplant-recipients
#10
Markus Riegersperger, Max Plischke, Corinna Steinhauser, Anita Jallitsch-Halper, Guerkan Sengoelge, Wolfgang C Winkelmayer, Gere Sunder-Plassmann, Manuela F Ouml Dinger
BACKGROUND: The multidrug resistance 1 gene (ABCB1) encodes P-glycoprotein (PGP), mainly expressed in the liver and engaged in metabolism of drugs including the immunosuppressant tacrolimus (TAC). ABCB1 single nucleotide polymorphisms (SNP) may significantly alter pharmacokinetics and influence TAC concentrations of kidney transplant recipients (KTR). METHODS: The genotype distribution of ABCB1 1236C>T, 2677G>T/A and 3435C>T was investigated among 96 Austrian KTR who were converted from cyclosporin to TAC...
October 1, 2016: Clinical Laboratory
https://www.readbyqxmd.com/read/28153721/mir-138-indirectly-regulates-the-mdr1-promoter-by-nf-%C3%AE%C2%BAb-p65-silencing
#11
J L Requenez-Contreras, E S López-Castillejos, R Hernández-Flores, M A Moreno-Eutimio, J T Granados-Riveron, G U Martinez-Ruiz, G Aquino-Jarquin
MicroRNAs (miRNAs) are known to mediate post-transcriptional gene silencing in the cytoplasm and recent evidence indicates that may also possess nuclear roles in regulating gene expression. A recent study showed that miR-138 is involved in the multidrug resistance of leukemia cells through down-regulation of the drug efflux pump P-glycoprotein (P-gp), the protein encoded by the human multidrug-resistant ABCB1/MDR1 gene. However, the transcriptional regulatory mechanisms responsible remain to be elucidated. To deepen the description of the mechanism of transcriptional gene silencing on the MDR1 promoter, we initially performed a bioinformatics search for potential miR-138 binding sites in the MDR1 gene promoter sequence...
January 30, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28151874/single-nucleotide-polymorphisms-of-abcb1-gene-and-response-to-etanercept-treatment-in-patients-with-ankylosing-spondylitis-in-a-chinese-han-population
#12
Rui-Jian Yan, Ting-Ting Lou, Yi-Fang Wu, Wei-Shan Chen
BACKGROUND: Etanercept was highly recommended for patients with ankylosing spondylitis (AS), as its efficacy has been confirmed in AS, while genetic polymorphisms, by affecting drug metabolism or drug receptor, lead to interindividual variability in drug disposition and efficacy. Therefore, this study aims to investigate whether ABCB1 gene polymorphisms can predict therapeutic response to etanercept in patients with AS. METHODS: A total of 185 patients with AS in our hospital were recruited into our study from December 2012 to May 2015...
February 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28145050/cytochrome-2b6-polymorphism-and-efavirenz-induced-central-nervous-system-symptoms-a-substudy-of-the-anrs-alize-trial
#13
S Gallien, V Journot, M-A Loriot, H Sauvageon, P Morlat, J Reynes, V Reliquet, G Chêne, J-M Molina
OBJECTIVES: Single nucleotide polymorphisms in the cytochrome P450 (CYP) 2B6 gene have been associated with high interindividual variation in efavirenz pharmacokinetics. However, clinical data on the relationship of CYP2B6 polymorphisms with the occurrence of efavirenz-induced central nervous system (CNS) symptoms are limited. METHODS: We analysed four polymorphisms in the CYP2B6 (516 G>T), CYP3A5 (6986 A>G) and ATP-binding cassette, sub-family B, member 1 (ABCB1) (2677 G>T/A and 3435 C>T) genes in HIV-infected adults virologically suppressed on a protease inhibitor-based regimen who switched to a regimen containing emtricitabine, didanosine and efavirenz in the setting of the ANRS ALIZE trial...
February 1, 2017: HIV Medicine
https://www.readbyqxmd.com/read/28143610/severe-toxicity-induced-by-accumulation-of-active-sunitinib-metabolite-in-a-japanese-patient-with-renal-cell-carcinoma-a-case-report
#14
Shinya Takasaki, Masafumi Kikuchi, Yoshihide Kawasaki, Akihiro Ito, Yoichi Arai, Hiroaki Yamaguchi, Nariyasu Mano
BACKGROUND: Sunitinib is a multi-targeted tyrosine kinase inhibitor that is approved for treatment of renal cell carcinoma as an oral anticancer drug. Therapeutic drug monitoring of total sunitinib (sunitinib and N-desethyl sunitinib) is used in our hospital to improve therapeutic efficacy, while preventing adverse effects. Here, we report the first case of a patient with metastatic renal cell carcinoma undergoing hemodialysis and presenting severe adverse events induced by the accumulation of N-desethyl sunitinib...
February 1, 2017: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/28135763/the-cyp2c19-2-and-cyp2c19-17-polymorphisms-play-a-vital-role-in-clopidogrel-responsiveness-after-percutaneous-coronary-intervention-a-pharmacogenomics-study
#15
Faruk Saydam, İrfan Değirmenci, Alparslan Birdane, Mahmut Özdemir, Taner Ulus, Cansu Özbayer, Ertuğrul Çolak, Necmi Ata, Hasan Veysi Güneş
Clopidogrel inhibits platelet activation and aggregation by blocking the P2Y12 receptor. Dual antiplatelet therapy with clopidogrel and aspirin is recommended treatment by current guidelines for patients undergoing percutaneous interventions. Recurrent ischaemic cardiac events after this treatment showed lack of clopidogrel responsiveness. We aimed to investigate the most noticeable variants in the genes involved in clopidogrel pharmacokinetics and pharmacodynamics. 347 Turkish patients who underwent percutaneous coronary interventions with stent implantation were included in our study...
January 30, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28135009/atp-binding-cassette-subfamily-b-member-1-1236c-t-polymorphism-significantly-affects-the-therapeutic-outcome-of-tacrolimus-in-patients-with-refractory-ulcerative-colitis
#16
Motoyuki Onodera, Katsuya Endo, Yoichi Kakuta, Masatake Kuroha, Tomoya Kimura, Keiichiro Hiramoto, Yoshitake Kanazawa, Kenichi Negoro, Hisashi Shiga, Yoshitaka Kinouchi, Tooru Shimosegawa
BACKGROUND AND AIM: Tacrolimus is now considered to be one of the main therapeutic options for refractory ulcerative colitis. Both cytochrome P-450 3A5 (CYP3A5) and ATP-binding cassette subfamily B member 1 (ABCB1) associated with tacrolimus metabolism are known to have several genetic polymorphisms. However, it remains controversial whether these polymorphisms affect the therapeutic efficacy for ulcerative colitis. We aimed to investigate the influence of both CYP3A5 and ABCB1 polymorphisms on the efficacy of tacrolimus in ulcerative colitis treatment under the tight dose-adjusting strategy...
January 30, 2017: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28134666/epithelioid-trophoblastic-tumor-around-an-abdominal-cesarean-scar-a-pathologic-and-molecular-genetic-analysis
#17
Emily Han-Chung Hsiue, Chiun Hsu, Li-Hui Tseng, Tzu-Pin Lu, Kuan-Ting Kuo
Epithelioid trophoblastic tumor (ETT) is a rare chemoresistant gestational trophoblastic neoplasm that typically presents as an intrauterine lesion. To our knowledge, no isolated abdominal wall ETT around a Cesarean scar has been reported. Here we describe a 54-yr-old woman with a complex obstetric history who presented with a solitary abdominal wall tumor adjacent to the abdominal Cesarean section scar. The tumor demonstrated typical morphologic and immunophenotypic features of ETT. The gestational origin of the tumor was confirmed by microsatellite genotyping...
January 27, 2017: International Journal of Gynecological Pathology
https://www.readbyqxmd.com/read/28126516/selenoesters-and-selenoanhydrides-as-novel-multidrug-resistance-reversing-agents-a-confirmation-study-in-a-colon-cancer-mdr-cell-line
#18
Márió Gajdács, Gabriella Spengler, Carmen Sanmartín, Małgorzata Anna Marć, Jadwiga Handzlik, Enrique Domínguez-Álvarez
Taking into account that multidrug resistance (MDR) is the main cause for chemotherapeutic failure in cancer treatment and as a continuation of our efforts to overcome this problem we report the evaluation of one cyclic selenoanhydride (1) and ten selenoesters (2-11) in MDR human colon adenocarcinoma Colo 320 cell line. The most potent derivatives (1, 9-11) inhibited the ABCB1 efflux pump much stronger than the reference compound verapamil. Particularly, the best one (9) was 4-fold more potent than verapamil at a 10-fold lower concentration...
January 13, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28125071/backstabbing-p-gp-side-chain-cleaved-ecdysteroid-2-3-dioxolanes-hyper-sensitize-mdr-cancer-cells-to-doxorubicin-without-efflux-inhibition
#19
Attila Hunyadi, József Csábi, Ana Martins, Joseph Molnár, Attila Balázs, Gábor Tóth
P-glycoprotein (P-gp, ABCB1) over-expression, causing a multi-drug resistant (MDR) phenotype, is a major problem in cancer chemotherapy that urgently requires novel approaches. Our previous studies showed certain ecdysteroid derivatives as promising chemo-sensitizers against MDR and non-MDR cancer cell lines while also exerting mild to moderate inhibition of P-gp function. Here we report the preparation of a set of substituted 2,3-dioxolane derivatives of poststerone, a known in vivo metabolite of 20-hydroxyecdysone (20E)...
January 25, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28119432/exploiting-ar-regulated-drug-transport-to-induce-sensitivity-to-the-survivin-inhibitor-ym155
#20
Michael D Nyquist, Alexandra Corella, John Burns, Ilsa Coleman, Shuai Gao, Robin Tharakan, Luke Riggan, Changmeng Cai, Eva Corey, Peter S Nelson, Elahe A Mostaghel
: Androgen receptor (AR) signaling is fundamental to prostate cancer and is the dominant therapeutic target in metastatic disease. However, stringent androgen deprivation therapy (ADT) regimens decrease quality of life and have been largely unsuccessful in curtailing mortality. Recent clinical and pre-clinical studies have taken advantage of the dichotomous ability of AR signaling to elicit growth-suppressive and differentiating effects by administering hyper-physiological levels of testosterone...
January 24, 2017: Molecular Cancer Research: MCR
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