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https://www.readbyqxmd.com/read/28429622/pharmacoepigenomic-responses-of-antipsychotic-drugs-on-pharmacogenes-are-likely-to-be-modulated-by-mirnas
#1
Babu Swathy, Koramannil R Saradalekshmi, Indu V Nair, Chandrasekharan Nair, Moinak Banerjee
AIM: It is imperative to differentiate the role of host epigenetics from pharmacoepigenetics in resolving therapeutic response. Therefore, the objective was to identify how antipsychotic drugs influence epigenetic response on pharmacogenes. MATERIALS & METHODS: The study design was based on in vitro evaluation of pharmacoepigenetic response of haloperidol, clozapine and olanzapine. Post antipsychotic treatment, the alterations in expression of ABCB1, CYP1A2 and CYP3A4 were monitored, and followed up by promoter methylation and their target miRNA expression studies...
April 21, 2017: Epigenomics
https://www.readbyqxmd.com/read/28428443/mechanisms-of-pinometostat-epz-5676-treatment-emergent-resistance-in-mll-rearranged-leukemia
#2
Carly T Campbell, Jessica N Haladyna, David A Drubin, Ty M Thomson, Michael J Maria, Taylor Yamauchi, Nigel J Waters, Edward J Olhava, Roy M Pollock, Jesse J Smith, Robert A Copeland, Stephen J Blakemore, Kathrin M Bernt, Scott R Daigle
DOT1L is a protein methyltransferase involved in the development and maintenance of MLL-rearranged (MLL-r) leukemia through its ectopic methylation of histones associated with well characterized leukemic genes.  Pinometostat (EPZ-5676), a selective inhibitor of DOT1L, is in clinical development in relapsed/refractory acute leukemia patients harboring rearrangements of the MLL gene. The observation of responses and subsequent relapses in the adult trial treating MLL-r patients motivated preclinical investigations into potential mechanisms of pinometostat treatment emergent resistance (TER) in cell lines confirmed to have MLL-r...
April 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28422980/genetic-and-epigenetic-changes-in-host-abcb1-influences-malaria-susceptibility-to-plasmodium-falciparum
#3
Himanshu Gupta, Sima Chaudhari, Ayushi Rai, Smitha Bhat, Pratima K Sahu, Manjunath H Hande, Sydney C D'Souza, Umakanth Shashikiran, Kapaettu Satyamoorthy
Multiple mechanisms such as genetic and epigenetic variations within a key gene may play a role in malarial susceptibility and response to anti-malarial drugs in the population. ABCB1 is one of the well-studied membrane transporter genes that code for the P-glycoprotein (an efflux protein) and whose effect on malaria disease predisposition and susceptibility to drugs remains to be understood. We studied the association of single nucleotide variations in human ABCB1 that influences its function in subjects with uncomplicated and complicated malaria caused by Plasmodium falciparum (Pf)...
2017: PloS One
https://www.readbyqxmd.com/read/28422712/combination-analysis-of-nos3-abcb1-and-il23r-polymorphisms-with-alcohol-induced-osteonecrosis-of-the-femoral-head-risk-in-chinese-males
#4
Yuan Wang, Xuejun Yang, Jianping Shi, Yan Zhao, Linlin Pan, Jinqiu Zhou, Guoqiang Wang, Jianzhong Wang
BACKGROUND: Common variants of multiple genes played a crucial role in osteonecrosis of the femoral head (ONFH) onset which was proved by many previous reports. We hypothesized that polymorphisms in NOS3, ABCB1 and IL23R were related to individual differences in alcohol sensitivity and the development of alcohol-induced ONFH. METHODS: In this case-control study, we evaluated 8 SNPs in three genes in the Chinese Han population including 355 male cases and 355 healthy male controls...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28421773/exploring-jolkinol-d-derivatives-to-overcome-multidrug-resistance-in-cancer
#5
Mariana A Reis, Omar B Ahmed, Gabriella Spengler, Joseph Molnár, Hermann Lage, Maria-José U Ferreira
Macrocyclic monoacyl lathyrane derivatives bearing a benzoyl moiety were previously found to be strong ABCB1 modulators. To explore the effects of different substituents of the aromatic moiety, 14 new compounds (1.1-1.7, 1.10, and 2.1-2.4) were prepared from jolkinol D (1), obtained from Euphorbia piscatoria, and from jolkinodiol (2), its hydrolysis derivative. Compounds 1.8 and 1.9, having aliphatic moieties, were also obtained. The reversal of ABCB1-mediated MDR was evaluated through functional and chemosensitivity assays on the human ABCB1-gene-transfected L5178Y mouse T-lymphoma cell line...
April 19, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28417539/usp22-mediates-the-multidrug-resistance-of-hepatocellular-carcinoma-via-the-sirt1-akt-mrp1-signaling-pathway
#6
Sunbin Ling, Jie Li, Qiaonan Shan, Haojiang Dai, Di Lu, Xue Wen, Penghong Song, Haiyang Xie, Lin Zhou, Jimin Liu, Xiao Xu, Shusen Zheng
Drug treatments for hepatocellular carcinoma (HCC) often fail because of multidrug resistance (MDR). The mechanisms of MDR are complex but cancer stem cells (CSC), which are able to self-renew and differentiate, have recently been shown to be involved. The deubiquitinating enzyme ubiquitin-specific protease 22 (USP22) is a marker for CSCs. This study aimed to elucidate the role of USP22 in MDR of HCC and the underlying mechanisms. Using in vitro and in vivo assays, we found that modified USP22 levels were responsible for the altered drug-resistant phenotype of BEL7402 and BEL/FU cells...
April 18, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28414325/hedgehog-signaling-pathway-affects-the-sensitivity-of-hepatoma-cells-to-drug-therapy-through-the-abcc1-transporter
#7
Jia Ding, Xiao-Tian Zhou, Hao-Yu Zou, Jian Wu
The poor response to drug therapy often seen in hepatocellular carcinoma requires insight into the molecular interplay responsible for intrinsic or acquired drug resistance. We previously demonstrated that the CD133(-)/EpCAM(-) subpopulation of the Huh-7 hepatoma cell line features aberrant activation of the hedgehog signaling (Hh) pathway and chemoresistance. The prevailing hypothesis of the present study is that hedgehog signaling may govern expression of ATP-binding cassette (ABC) transporters, which are responsible for drug resistance in the CD133(-)/EpCAM(-) subpopulation...
April 17, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28411377/mir-495-sensitizes-mdr-cancer-cells-to-the-combination-of-doxorubicin-and-taxol-by-inhibiting-mdr1-expression
#8
Zhenyou Zou, Ruyi Zou, Dan Zong, Yonghong Shi, Jinyao Chen, Jie Huang, Jiahui Zhu, Liguan Chen, Xiaoyan Bao, Yuan Liu, Weihao Liu, Wenhui Huang, Jingsang Hu, Zhi Chen, Xiaojie Lao, Chaoqun Chen, Xiaoli Huang, Yao Lu, Xueyin Ni, Daoquan Fang, Dengqiang Wu, Shuangshuang Lu, Mingzhu Jiang, Chenyang Qiu, Yuya Wu, Qisha Qiu, Yanyuan Dong, Yangyang Su, Chenmin Zhao, Zhihe Zhong, Jing Cai, Yong Liang
MDR1 is highly expressed in MDR A2780DX5 ovarian cancer cells, MDR SGC7901R gastric cancer cells and recurrent tumours. It pumps cytoplasmic agents out of cells, leading to decreased drug accumulation in cells and making cancer cells susceptible to multidrug resistance. Here, we identified that miR-495 was predicted to target ABCB1, which encodes protein MDR1. To reduce the drug efflux and reverse MDR in cancer cells, we overexpressed a miR-495 mimic in SGC7901R and A2780DX cells and in transplanted MDR ovarian tumours in vivo...
April 14, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28408210/the-organic-anion-transporting-peptide-oatp-2b1-is-localized-in-the-basolateral-membrane-of-the-human-jejunum-and-caco-2-monolayers
#9
Markus Keiser, Lars Kaltheuner, Charlotte Wildberg, Janett Müller, Markus Grube, Lars Ivo Partecke, Claus-Dieter Heidecke, Stefan Oswald
The organic anion transporting polypeptide (OATP) 2B1 which is ubiquitously expressed in the human body is assumed to play an important role in the cellular uptake of many drugs. While the expression and function of this SLC transporter is well characterized in the human liver, little is known about its localization and functional relevance in the intestine. Thus, it was the aim of this study to investigate its localization and function in the human jejunum and in the frequently used intestinal Caco-2 cell line...
April 10, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28401570/effect-of-p-glycoprotein-inhibition-at-the-blood-brain-barrier-on-brain-distribution-of-r-11-c-verapamil-in-elderly-versus-young-subjects
#10
Martin Bauer, Beatrix Wulkersdorfer, Rudolf Karch, Cécile Philippe, Walter Jäger, Johann Stanek, Wolfgang Wadsak, Marcus Hacker, Markus Zeitlinger, Oliver Langer
AIMS: The efflux transporter P-glycoprotein (ABCB1) restricts at the blood-brain barrier (BBB) distribution of many different drugs from blood to the brain. Previous data suggest an age-associated decrease in the expression and function of ABCB1 at the BBB. In this study we investigated the influence of age on the magnitude of an ABCB1-mediated drug-drug interaction (DDI) at the BBB. METHODS: We performed positron emission tomography (PET) scans with the model ABCB1 substrate (R)-[(11) C]verapamil in five young (26 ± 1 years, [mean ± standard deviation]) and five elderly (68 ± 6 years) healthy male volunteers before and after intravenous administration of a low dose of the ABCB1 inhibitor tariquidar (3 mg kg(-1) )...
April 12, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28399108/decreased-levels-of-baseline-and-drug-induced-tubulin-polymerisation-are-hallmarks-of-resistance-to-taxanes-in-ovarian-cancer-cells-and-are-associated-with-epithelial-to-mesenchymal-transition
#11
George E Duran, Yan C Wang, François Moisan, E Brian Francisco, Branimir I Sikic
BACKGROUND: ABCB1 expression is uncommon in ovarian cancers in the clinical setting so we investigated non-MDR mechanisms of resistance to taxanes. METHODS: We established eight taxane-resistant variants from the human ovarian carcinoma cell lines A2780/1A9, ES-2, MES-OV and OVCAR-3 by selection with paclitaxel or docetaxel, with counter-selection by the transport inhibitor valspodar. RESULTS: Non-MDR taxane resistance was associated with reduced intracellular taxane content compared to parental controls, and cross-resistance to other microtubule stabilising drugs...
April 11, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28398354/global-genetic-variation-of-select-opiate-metabolism-genes-in-self-reported-healthy-individuals
#12
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/28389777/contribution-of-tumor-endothelial-cells-to-drug-resistance-anti-angiogenic-tyrosine-kinase-inhibitors-act-as-p-glycoprotein-antagonists
#13
MariaRosa Bani, Alessandra Decio, Raffaella Giavazzi, Carmen Ghilardi
Tumor endothelial cells (TEC) differ from the normal counterpart, in both gene expression and functionality. TEC may acquire drug resistance, a characteristic that is maintained in vitro. There is evidence that TEC are more resistant to chemotherapeutic drugs, substrates of ATP-binding cassette (ABC) transporters. TEC express p-glycoprotein (encoded by ABCB1), while no difference in other ABC transporters was revealed compared to normal endothelia. A class of tyrosine kinase inhibitors (TKI), used as angiostatic compounds, interferes with the ATPase activity of p-glycoprotein, thus impairing its functionality...
April 7, 2017: Angiogenesis
https://www.readbyqxmd.com/read/28388599/abcb1-genotype-is-associated-with-fentanyl-requirements-in-critically-ill-children
#14
Christopher M Horvat, Alicia K Au, Yvette L Conley, Patrick M Kochanek, Lingjue Li, Samuel L Poloyac, Philip E Empey, Robert S B Clark
BACKGROUND: The gene ABCB1 encodes p-glycoprotein, a xenobiotic efflux pump capable of transporting certain opioids, including fentanyl. ABCB1 genotype has been previously associated with patient opioid requirements and may influence fentanyl dosing requirements in critically ill children. METHODS: A diagnostically diverse cohort of 61 children who received a fentanyl infusion while admitted to the pediatric intensive care unit (PICU) were included in this study...
April 7, 2017: Pediatric Research
https://www.readbyqxmd.com/read/28383515/abc-transport-proteins-in-cardiovascular-disease-a-brief-summary
#15
REVIEW
Toni Schumacher, Ralf A Benndorf
Adenosine triphosphate (ATP)-binding cassette (ABC) transporters may play an important role in the pathogenesis of atherosclerotic vascular diseases due to their involvement in cholesterol homeostasis, blood pressure regulation, endothelial function, vascular inflammation, as well as platelet production and aggregation. In this regard, ABC transporters, such as ABCA1, ABCG5 and ABCG8, were initially found to be responsible for genetically-inherited syndromes like Tangier diseases and sitosterolemia. These findings led to the understanding of those transporter's function in cellular cholesterol efflux and thereby also linked them to atherosclerosis and cardiovascular diseases (CVD)...
April 6, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28381801/association-of-single-nucleotide-polymorphisms-in-stat3-abcb1-and-abcg2-with-stomatitis-in-patients-with-metastatic-renal-cell-carcinoma-treated-with-sunitinib-a-retrospective-analysis-in-japanese-patients
#16
Aimi Watanabe, Kazuhiro Yamamoto, Takeshi Ioroi, Sachi Hirata, Kenichi Harada, Hideaki Miyake, Masato Fujisawa, Tsutomu Nakagawa, Ikuko Yano, Midori Hirai
Signal transducer and activator of transcription (STAT) 3 is a key factor in homeostasis of the oral mucosa by regulating the production of inflammatory cytokines. Sunitinib is a substrate of P-glycoprotein (multidrug resistance (MDR)-1/ABCB1) and breast-cancer resistance protein (BCRP/ABCG2). In this retrospective study, we evaluated the association between sunitinib-induced stomatitis and STAT3, ABCB1, and ABCG2 polymorphisms in patients with metastatic renal cell carcinoma (mRCC). Fifty-two Japanese patients with RCC treated with sunitinib were retrospectively genotyped to elucidate a potential association between STAT3, ABCB1, and ABCG2 polymorphisms and stomatitis development...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28380010/application-of-jc1-for-non-toxic-isolation-of-cells-with-mdr-transporter-activity-by-flow-cytometry
#17
J Mario Wolosin, Aldo Zamudio, Zheng Wang
The DNA intercalating dye Hoechst 33342 or its close analog DCV are actively removed from cells by the multidrug resistance transporter ABCG2, a protein overexpressed in metastatic cells and somatic stem cells. In bivariate blue-red flow cytometry fluorescent plots active Hoechst or DCV efflux combined with a concentration dependent bathochromic shifts of these nuclear dyes leads to the segregation of the transporter-rich cells into a distinct cell cohort tilted towards the shorter wavelength axis of the plot, the cohort is generically known as the side population (SP)...
2017: PloS One
https://www.readbyqxmd.com/read/28379874/effects-of-single-nucleotide-polymorphisms-on-surgical-and-post-surgical-opioid-requirements-a-systematic-review-and-meta-analysis
#18
Siu-Wai Choi, David M H Lam, Stanley S C Wong, Haydn H C Shiu, Amy X M Wang, Chi-Wai Cheung
OBJECTIVES: There is great heterogeneity in the way individuals respond to medications. Inherited differences, such as Single Nucleotide Polymorphisms (SNP), can influence the efficacy and toxicity of drugs. This meta-analysis aims to collate data from studies investigating the effect of SNPs on post-operative and/or intra-operative opioid requirements. METHODS: This meta-analysis was conducted following PRISMA guidelines. Eligibility criteria for studies in this meta-analysis were reporting amount of post-operative and/or intra-operative opioid used as the primary outcome and genotyping patients for SNPs in one of the following genes; OPRM1, CYP2D6, CYP3A4, CYP3A5, COMT, UGT2B7 or ABCB1...
April 4, 2017: Clinical Journal of Pain
https://www.readbyqxmd.com/read/28378058/meta-analysis-of-effects-of-abcb1-polymorphisms-on-clopidogrel-response-among-patients-with-coronary-artery-disease
#19
Yajing Zhai, Hairong He, Xiancang Ma, Jiao Xie, Ti Meng, Yalin Dong, Jun Lu
PURPOSE: The substantial variability in the antiplatelet efficacy of clopidogrel has raised major concerns. Molecular epidemiological research suggests that ABCB1 C3435T polymorphism may be associated with clopidogrel response, but results remain controversial. To derive a more precise evaluation of the associations between ABCB1 C3435T polymorphism and the clinical efficacy of clopidogrel, we have conducted a PRISMA-compliant meta-analysis. METHODS: The PubMed and EMBASE databases were searched for eligible studies up to 25 October 2016...
April 5, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28373423/new-and-old-genes-associated-with-topotecan-resistance-development-in-ovarian-cancer-cell-lines
#20
Andrzej Klejewski, Monika Świerczewska, Katarzyna Zaorska, Maciej Brązert, Michał Nowicki, Maciej Zabel, Radosław Januchowski
BACKGROUND: Low effectiveness of chemotherapy in ovarian cancer results from development of drug resistance. Topotecan is a drug used as second-line chemotherapy for this cancer type. We analyzed development of topotecan resistance in ovarian cancer cell lines. MATERIALS AND METHODS: A chemosensitivity assay, MTT test, was performed to assess drug resistance. Quantitative polymerase chain reaction (Q-PCR) assays were performed to determine ABCB1, ABCG2, ALDH1A1, IFIH1, SAMD4 and EPHA3 gene expression...
April 2017: Anticancer Research
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