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https://www.readbyqxmd.com/read/28900313/selective-atp-binding-cassette-subfamily-c-gene-expression-and-proinflammatory-mediators-released-by-beas-2b-after-pm2-5-budesonide-and-cotreated-exposures
#1
Jarline Encarnación-Medina, Rosa I Rodríguez-Cotto, Joseph Bloom-Oquendo, Mario G Ortiz-Martínez, Jorge Duconge, Braulio Jiménez-Vélez
ATP-binding cassette subfamily C (ABCC) genes code for phase III metabolism proteins that translocate xenobiotic (e.g., particulate matter 2.5 (PM2.5)) and drug metabolites outside the cells. IL-6 secretion is related with the activation of the ABCC transporters. This study assesses ABCC1-4 gene expression changes and proinflammatory cytokine (IL-6, IL-8) release in human bronchial epithelial cells (BEAS-2B) exposed to PM2.5 organic extract, budesonide (BUD, used to control inflammation in asthmatic patients), and a cotreatment (Co-T: PM2...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28885828/multidrug-resistance-protein-4-mrp4-abcc4-protects-cells-from-the-toxic-effects-of-halobenzoquinones
#2
Jinhua Li, Madlen Bauer, Birget Moe, Elaine M Leslie, Xing-Fang Li
Halobenzoquinones (HBQs) are frequently detected disinfection byproducts (DBPs) in treated water. Recent studies have demonstrated that HBQs are highly cytotoxic and capable of inducing the generation of reactive oxygen species (ROS) and depleting cellular glutathione (GSH). Multidrug resistance proteins (MRPs/ABCCs) are known to play a critical role in the elimination of numerous drugs, carcinogens, toxicants, and their conjugated metabolites. In general, little is known about the roles of transporters in DBP toxicity...
September 8, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28883280/susceptibility-to-6-mercaptopurine-toxicity-related-with-nudt15-and-abcc4-variants-in-japanese-childhood-acute-lymphoblastic-leukemia
#3
Yoichi Tanaka
6-Mercaptopurine (6-MP) is one of the main components for the treatment of childhood acute lymphoblastic leukemia (ALL). However, many patients require a dose reduction of 6-MP due to its severe toxicities. NUDT15 variants are one of the factors that cause 6-MP intolerability in Asians. In each patient with heterozygous variants of NUDT15, 6-MP intolerability differs. Therefore, we hypothesized that the combination of NUDT15 genotype with ABCC4 genotype, which is associated with 6-MP efflux, might enable to accurately predict 6-MP intolerability...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28882023/apex1-polymorphism-and-mercaptopurine-related-early-onset-neutropenia-in-pediatric-acute-lymphoblastic-leukemia
#4
Hyery Kim, Heewon Seo, Yoomi Park, Byung-Joo Min, Myung-Eui Seo, Kyung Duk Park, Hee Young Shin, Ju Han Kim, Hyoung Jin Kang
Purpose: Mercaptopurine (MP) is one of the main chemotherapeutics for acute lymphoblastic leukemia (ALL). To improve treatment outcomes, constant MP dose titration is essential to maintain steady drug exposure, while minimizing myelosuppression. We performed two-stage analyses to identify genetic determinants of MP-related neutropenia in Korean pediatric ALL patients. Materials and Methods: Targeted sequencing of 40 patients who exhibited definite MP intolerance was conducted using a novel panel of 211 pharmacogenetic-related genes, and subsequent analysis was performed with 185 patients...
September 4, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28863172/regulation-of-xanthine-dehydrogensase-gene-expression-and-uric-acid-production-in-human-airway-epithelial-cells
#5
Ryan D Huff, Alan C-Y Hsu, Kristy S Nichol, Bernadette Jones, Darryl A Knight, Peter A B Wark, Philip M Hansbro, Jeremy A Hirota
INTRODUCTION: The airway epithelium is a physical and immunological barrier that protects the pulmonary system from inhaled environmental insults. Uric acid has been detected in the respiratory tract and can function as an antioxidant or damage associated molecular pattern. We have demonstrated that human airway epithelial cells are a source of uric acid. Our hypothesis is that uric acid production by airway epithelial cells is induced by environmental stimuli associated with chronic respiratory diseases...
2017: PloS One
https://www.readbyqxmd.com/read/28765596/a-polymorphism-in-abcc4-is-related-to-efficacy-of-5-fu-capecitabine-based-chemotherapy-in-colorectal-cancer-patients
#6
Qi Chen, Fanyi Meng, Lei Wang, Yong Mao, Huan Zhou, Dong Hua, Hongjian Zhang, Weipeng Wang
To investigate the association of microRNA (miRNA) binding-site polymorphisms in the drug transporter genes with the efficacy of 5-Fluorouracil (5-FU)/capecitabine-based chemotherapy in colorectal cancer (CRC), 6 polymorphisms were determined in 432 CRC patients by using DNA sequencing method. The impacts of the polymorphisms on the miRNA-mediated regulation of gene expression were evaluated by using the methods including quantitative real-time PCR, western blotting, and luciferase reporter assays. The effects of miRNA on the intracellular concentration and cytotoxicity of 5-FU in CRC cells were measured by high performance liquid chromatography conjected tandem mass spectrometry (HPLC-MS/MS) and MTT methods, respectively...
August 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28745575/use-of-exome-sequencing-to-determine-the-full-profile-of-genetic-variants-in-the-fluoropyrimidine-pathway-in-colorectal-cancer-patients-affected-by-severe-toxicity
#7
Marta Pellicer, Xandra García-González, María I García, Carolina Blanco, Pilar García-Alfonso, Luis Robles, Cristina Grávalos, Daniel Rueda, Joaquín Martínez, Vanessa Pachón, Federico Longo, Virginia Martínez, Irene Iglesias, Sara Salvador, María Sanjurjo, Luis A López-Fernández
AIM: To identify genetic variants associated with capecitabine toxicity in fluoropyrimidine pathway genes using exome sequencing. PATIENTS & METHODS: Exomes from eight capecitabine-treated patients with severe adverse reactions (grade >2), among a population of 319, were sequenced (Ion Proton). SNPs in genes classified as potentially damaging (Sorting Intolerant from Tolerant and Polymorphism Phenotyping v2) were tested for association with toxicity in a validation cohort of 319 capecitabine-treated patients...
August 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28735070/suppression-of-the-atp-binding-cassette-transporter-abcc4-impairs-neuroblastoma-tumour-growth-and-sensitises-to-irinotecan-in%C3%A2-vivo
#8
Jayne Murray, Emanuele Valli, Denise M T Yu, Alan M Truong, Andrew J Gifford, Georgina L Eden, Laura D Gamble, Kimberley M Hanssen, Claudia L Flemming, Alvin Tan, Amanda Tivnan, Sophie Allan, Federica Saletta, Leanna Cheung, Michelle Ruhle, John D Schuetz, Michelle J Henderson, Jennifer A Byrne, Murray D Norris, Michelle Haber, Jamie I Fletcher
The ATP-binding cassette transporter ABCC4 (multidrug resistance protein 4, MRP4) mRNA level is a strong predictor of poor clinical outcome in neuroblastoma which may relate to its export of endogenous signalling molecules and chemotherapeutic agents. We sought to determine whether ABCC4 contributes to development, growth and drug response in neuroblastoma in vivo. In neuroblastoma patients, high ABCC4 protein levels were associated with reduced overall survival. Inducible knockdown of ABCC4 strongly inhibited the growth of human neuroblastoma cells in vitro and impaired the growth of neuroblastoma xenografts...
September 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28725001/2-3-7-8-tetrachlorodibenzo-p-dioxin-tcdd-elicited-effects-on-bile-acid-homeostasis-alterations-in-biosynthesis-enterohepatic-circulation-and-microbial-metabolism
#9
Kelly A Fader, Rance Nault, Chen Zhang, Kazuyoshi Kumagai, Jack R Harkema, Timothy R Zacharewski
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental contaminant which elicits hepatotoxicity through activation of the aryl hydrocarbon receptor (AhR). Male C57BL/6 mice orally gavaged with TCDD (0.01-30 µg/kg) every 4 days for 28 days exhibited bile duct proliferation and pericholangitis. Mass spectrometry analysis detected a 4.6-fold increase in total hepatic bile acid levels, despite the coordinated repression of genes involved in cholesterol and primary bile acid biosynthesis including Cyp7a1...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28710036/effect-of-polymorphisms-in-transporter-genes-on-dosing-efficacy-and-toxicity-of-maintenance-therapy-in-children-with-acute-lymphoblastic-leukemia
#10
Guillermo Gervasini, Silvia G de Murillo, Mercedes Jiménez, María D de la Maya, Jose M Vagace
The aim of the present work was to assess whether polymorphisms in genes coding for drug transport proteins may influence dosing, efficacy and toxicity of maintenance therapy with methotrexate (MTX) and 6-mercaptopurine (6MP) in childhood acute lymphoblastic leukemia (ALL). A total of 41 children with ALL were screened for 10 SNPs in the SLC19A1, ABCB1, ABCC2, ABCC4 and ABCG2 transporter genes by means of direct sequencing. Carriers of the ABCC4 934CC and ABCB1 1236TT genotypes received a lower percentage of the protocol-recommended starting dose of MTX (62...
July 11, 2017: Gene
https://www.readbyqxmd.com/read/28677646/quantitative-evaluation-of-drug-resistance-profile-of-cells-expressing-wild-type-or-genetic-polymorphic-variants-of-the-human-abc-transporter-abcc4
#11
Megumi Tsukamoto, Shiori Sato, Kazuhiro Satake, Mizuki Miyake, Hiroshi Nakagawa
Broad-spectrum resistance in cancer cells is often caused by the overexpression of ABC transporters; which varies across individuals because of genetic single-nucleotide polymorphisms (SNPs). In the present study; we focused on human ABCC4 and established cells expressing the wild-type (WT) or SNP variants of human ABCC4 using the Flp-In™ system (Invitrogen, Life Technologies Corp, Carlsbad, CA, USA) based on Flp recombinase-mediated transfection to quantitatively evaluate the effects of nonsynonymous SNPs on the drug resistance profiles of cells...
July 4, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28659663/a-role-of-the-abcc4-gene-polymorphism-in-airway-inflammation-of-asthmatics
#12
Sailesh Palikhe, Udval Uuganbayar, Hoang Kim Tu Trinh, Ga-Young Ban, Eun-Mi Yang, Hae-Sim Park, Seung-Hyun Kim
The ATP-binding cassette subfamily C member 4 gene encodes a transmembrane protein involved in the export of proinflammatory molecules, including leukotriene, prostaglandin, and sphingosine-1-phosphate across the plasma membrane. Those metabolites play important roles in asthma. We investigated the potential associations between ABCC4 gene polymorphisms and asthma phenotype. In total, 270 asthma patients and 120 normal healthy controls were enrolled for a genetic association study. Two polymorphisms (-1508A>G and -642C>G) in the ABCC4 promoter were genotyped...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28626473/clinical-applicability-of-whole-exome-sequencing-exemplified-by-a-study-in-young-adults-with-the-advanced-cryptogenic-cholestatic-liver-diseases
#13
Maria Kulecka, Andrzej Habior, Agnieszka Paziewska, Krzysztof Goryca, Michalina Dąbrowska, Filip Ambrozkiewicz, Bożena Walewska-Zielecka, Andrzej Gabriel, Michal Mikula, Jerzy Ostrowski
BACKGROUND: The proper use of new medical tests in clinical practice requires the establishment of their value and range of diagnostic usefulness. While whole-exome sequencing (WES) has already entered the medical practice, recognizing its diagnostic usefulness in multifactorial diseases has not yet been achieved. AIMS: The objective of this study was to establish usability of WES in determining genetic background of chronic cholestatic liver disease (CLD) in young patients...
2017: Gastroenterology Research and Practice
https://www.readbyqxmd.com/read/28583112/clinical-and-genetic-factors-associated-with-kidney-tubular-dysfunction-in-a-real-life-single-centre-cohort-of-hiv-positive-patients
#14
S E Salvaggio, A Giacomelli, F S Falvella, M L Oreni, P Meraviglia, C Atzori, E G I Clementi, M Galli, S Rusconi
BACKGROUND: Tenofovir (TDF) is one of the most widely used antiretroviral drug. Despite the high degree of tolerability a small percentage of patients experienced alteration in tubular function during TDF use. Intracellular TDF disposition is regulated by ATP-binding cassette (ABC) drug efflux transporters and, a reduced transport activity may be implicated in accumulation of TDF into the cells. The aim of our study was to assess the major determinants of TDF associated tubular dysfunction (KTD) in a real-life setting including the usefulness of single-nucleotide polymorphisms (SNPs) mapping into ABCC2, ABCC4 and ABCC10 genes...
June 5, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28550450/abcc4-functional-snp-in-the-3-splice-acceptor-site-of-exon-8-g912t-is-associated-with-unfavorable-clinical-outcome-in-children-with-acute-lymphoblastic-leukemia
#15
Hamzeh Mesrian Tanha, Soheila Rahgozar, Marjan Mojtabavi Naeini
OBJECTIVES: ATP-binding cassette subfamily C member 4 (ABCC4) encoding MRP4 protein is involved in pediatric acute lymphoblastic leukemia (ALL) drug resistance. The nonsynonymous single nucleotide polymorphism (SNP) rs2274407 (G912T; K304N) is located in the 3' splice acceptor site of exon 8 of ABCC4 pre-mRNA. The aim of this study was to investigate the prognostic value of rs2274407 in childhood ALL and its possible functional effect on MRP4. METHODS: ABCC4 G912T SNP was genotyped in 145 Iranian Philadelphia-negative (Ph(-)) children with ALL using modified tetra-primer ARMS PCR and evaluated for possible association with 3-year disease-free survival (3DFS)...
July 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28456721/investigation-of-the-importance-of-multidrug-resistance-associated-protein-4-mrp4-abcc4-in-the-active-efflux-of-anionic-drugs-across-the-blood-brain-barrier
#16
Kayoko Kanamitsu, Hiroyuki Kusuhara, John D Schuetz, Kenji Takeuchi, Yuichi Sugiyama
The importance of multidrug resistance-associated protein 4 (Mrp4/Abcc4) in limiting the penetration of Mrp4 substrate compounds into the central nervous system across the blood-brain barrier was investigated using Mrp4(-/-) mice. Significant adenosine triphosphate-dependent uptake by MRP4 was observed for ochratoxin A, pitavastatin, raltitrexed (Km = 43.7 μM), pravastatin, cyclic guanosine monophosphate, 2,4-dichlorophenoxyacetate, and urate. The defect in the Mrp4 gene did not affect the brain-to-plasma ratio (Kp,brain) of quinidine and dantrolene...
April 27, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28418010/interaction-between-nudt15-and-abcc4-variants-enhances-intolerability-of-6-mercaptopurine-in-japanese-patients-with-childhood-acute-lymphoblastic-leukemia
#17
Y Tanaka, H Nakadate, K Kondoh, K Nakamura, K Koh, A Manabe
6-Mercaptopurine (6-MP) is a main component of childhood acute lymphoblastic leukemia (ALL) treatment. Some candidate gene variants are associated with its toxicities, but the major variants and effects of combined variants remain unclear. We used Cox regression analysis to evaluate the time-dependent association between candidate variants and the cumulative incidence of 6-MP intolerability in 95 Japanese patients. The major risk factors for severe leukopenia were ABCC4 rs3765534, NUDT15 rs116855232 and rs186364861 in multi-covariate analysis (P<0...
April 18, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28371506/population-specific-resequencing-associates-the-atp-binding-cassette-subfamily-c-member-4-gene-with-gout-in-new-zealand-m%C3%A4-ori-and-pacific-men
#18
Callum Tanner, James Boocock, Eli A Stahl, Amanda Dobbyn, Asim K Mandal, Murray Cadzow, Amanda J Phipps-Green, Ruth K Topless, Jennie Harré Hindmarsh, Lisa K Stamp, Nicola Dalbeth, Hyon K Choi, David B Mount, Tony R Merriman
OBJECTIVE: There is no evidence for a genetic association between organic anion transporters 1-3 (SLC22A6, SLC22A7, and SLC22A8) and multidrug resistance protein 4 (MRP4; encoded by ABCC4) with the levels of serum urate or gout. The Māori and Pacific (Polynesian) population of New Zealand has the highest prevalence of gout worldwide. The aim of this study was to determine whether any Polynesian population-specific genetic variants in SLC22A6-8 and ABCC4 are associated with gout. METHODS: All participants had ≥3 self-reported Māori and/or Pacific grandparents...
July 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28298215/nrf2-signaling-increases-expression-of-atp-binding-cassette-subfamily-c-mrna-transcripts-at-the-blood-brain-barrier-following-hypoxia-reoxygenation-stress
#19
Kathryn Ibbotson, Joshua Yell, Patrick T Ronaldson
BACKGROUND: Strategies to maintain BBB integrity in diseases with a hypoxia/reoxygenation (H/R) component involve preventing glutathione (GSH) loss from endothelial cells. GSH efflux transporters include multidrug resistance proteins (Mrps). Therefore, characterization of Mrp regulation at the BBB during H/R is required to advance these transporters as therapeutic targets. Our goal was to investigate, in vivo, regulation of Abcc1, Abcc2, and Abcc4 mRNA expression (i.e., genes encoding Mrp isoforms that transport GSH) by nuclear factor E2-related factor (Nrf2) using a well-established H/R model...
March 16, 2017: Fluids and Barriers of the CNS
https://www.readbyqxmd.com/read/28274777/impact-of-endotoxin-on-the-expression-of-drug-transporters-in-the-placenta-of-hiv-1-transgenic-hiv-tg-rats
#20
Ragia H Ghoneim, Dea Kojovic, Micheline Piquette-Miller
BACKGROUND: Inflammatory responses in HIV (+) patients may be exacerbated due to reports of subclinical endotoxemia and existing immune dysregulation. As inflammation has been reported to mediate changes in the expression of transporters, this could be potentiated in pregnant HIV (+) women. Similar to humans, the HIV-Tg rat model develops immune dysregulation and chronic AIDS-like conditions. Our objective was to examine the expression of placental drug transporters in HIV-Tg rats in response to low-dose endotoxin...
March 6, 2017: European Journal of Pharmaceutical Sciences
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