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https://www.readbyqxmd.com/read/29352151/effects-of-genetic-variants-on-platelet-reactivity-and-one-year-clinical-outcomes-after-percutaneous-coronary-intervention-a-prospective-multicentre-registry-study
#1
Hyung Joon Joo, Sung Gyun Ahn, Jae Hyoung Park, Ji Young Park, Soon Jun Hong, Seok-Yeon Kim, WoongGil Choi, HyeonCheol Gwon, Young-Hyo Lim, Weon Kim, Woong Chol Kang, Yun-Hyeong Cho, Yong Hoon Kim, JungHan Yoon, WonYong Shin, Myeong-Ki Hong, Scot Garg, Yangsoo Jang, Do-Sun Lim
Clopidogrel is the mainstay for antiplatelet treatment after percutaneous coronary intervention (PCI). The relationship of platelet reactivity and genetic polymorphism with clinical outcomes with newer-generation drug-eluting stents is unclear. We analysed 4,587 patients for the most powerful single-nucleotide polymorphisms (CYP2C19, CYP2C9, ABCB1, PON1, and P2Y12) related to on-treatment platelet reactivity (OPR). The optimal cut-off value of high OPR for major adverse thrombotic events was 266. CYP2C19 was significantly associated with high OPR and the number of CYP2C19*R (*2 or *3) alleles was proportional to the increased risk of high OPR...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29350207/association-between-cyp2c19-and-abcb1-polymorphisms-and-clopidogrel-resistance-in-clopidogrel-treated-chinese-patients
#2
Zhong Ling Zhuo, Hai Peng Xian, Yan Long, Chang Liu, Yuan Yuan Sun, Yin Ting Ma, Hua Gao, Jing Zhong Zhao, Xiao Tao Zhao
OBJECTIVE: To investigate the association between CYP2C19 and ABCB1 polymorphisms and clopidogrel resistance (CR) in patients with cardiovascular disease in Beijing district. METHODS: In total, 325 patients were enrolled in the study, including 101 experimental group patients and 224 control group patients. The experimental group was divided into CR group (n=30) and non-CR group (n=71) according to the adenosine diphosphate (ADP)-induced platelet inhibition rate in thromboelastography (TEG) (ADP-induced platelet inhibition rate of <30% was defined as CR and rate of 30%-100% was defined as non-CR)...
January 19, 2018: Anatolian Journal of Cardiology
https://www.readbyqxmd.com/read/29342177/a-new-fluorescent-dye-accumulation-assay-for-parallel-measurements-of-the-abcg2-abcb1-and-abcc1-multidrug-transporter-functions
#3
Edit Szabó, Dóra Türk, Ágnes Telbisz, Nóra Kucsma, Tamás Horváth, Gergely Szakács, László Homolya, Balázs Sarkadi, György Várady
ABC multidrug transporters are key players in cancer multidrug resistance and in general xenobiotic elimination, thus their functional assays provide important tools for research and diagnostic applications. In this study we have examined the potential interactions of three key human ABC multidrug transporters with PhenGreen diacetate (PGD), a cell permeable fluorescent metal ion indicator. The non-fluorescent, hydrophobic PGD rapidly enters the cells and, after cleavage by cellular esterases, in the absence of quenching metal ions, PhenGreen (PG) becomes highly fluorescent...
2018: PloS One
https://www.readbyqxmd.com/read/29340049/pharmacological-treatment-with-inhibitors-of-nuclear-export-enhances-the-antitumor-activity-of-docetaxel-in-human-prostate-cancer
#4
Giovanni Luca Gravina, Andrea Mancini, Alessandro Colapietro, Francesco Marampon, Roberta Sferra, Simona Pompili, Leda Assunta Biordi, Roberto Iorio, Vincenzo Flati, Christian Argueta, Yosef Landesman, Michael Kauffman, Sharon Shacham, Claudio Festuccia
Background and aims: Docetaxel (DTX) modestly increases patient survival of metastatic castration-resistant prostate cancer (mCRPC) due to insurgence of pharmacological resistance. Deregulation of Chromosome Region Maintenance (CRM-1)/ exportin-1 (XPO-1)-mediated nuclear export may play a crucial role in this phenomenon. Material and methods: Here, we evaluated the effects of two Selective Inhibitor of Nuclear Export (SINE) compounds, selinexor (KPT-330) and KPT-251, in association with DTX by using 22rv1, PC3 and DU145 cell lines with their...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29340035/abcb1-3435tt-and-abcg2-421cc-genotypes-were-significantly-associated-with-longer-progression-free-survival-in-chinese-breast-cancer-patients
#5
Wanjun Li, Dan Zhang, Fen Du, Xuemei Xing, Ying Wu, Dong Xiao, Ming Liang, Zhigang Fan, Peng Zhao, Tao Liu, Guoyin Li
Objective: To investigate the distribution of ABCB1 C3435T and ABCG2 C421A gene polymorphisms in Chinese Han population and their influences on the susceptibility and prognosis of breast carcinoma. Methods: A total of 200 female subjects were enrolled in this study, comprising 100 breast cancer patients and 100 healthy controls. Carcinoma and para-carcinoma tissues were collected from the breast cancer patients, while peripheral blood was collected from healthy controls...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29337087/genetic-polymorphisms-of-pharmacogenomic-vip-variants-in-the-yi-population-from-china
#6
Mengdan Yan, Dianzhen Li, Guige Zhao, Jing Li, Fanglin Niu, Bin Li, Peng Chen, Tianbo Jin
INTRODUCTION: Drug response and target therapeutic dosage are different among individuals. The variability is largely genetically determined. With the development of pharmacogenetics and pharmacogenomics, widespread research have provided us a wealth of information on drug-related genetic polymorphisms, and the very important pharmacogenetic (VIP) variants have been identified for the major populations around the world whereas less is known regarding minorities in China, including the Yi ethnic group...
January 11, 2018: Gene
https://www.readbyqxmd.com/read/29334793/controlled-synthesis-and-size-effects-of-multifunctional-mesoporous-silica-nanosystem-for-precise-cancer-therapy
#7
Bin Ma, Lizhen He, Yuanyuan You, Jianbin Mo, Tianfeng Chen
Nanomaterials-based drug delivery systems display potent applications in cancer therapy, owing to the enhanced permeability and retention effect and diversified chemical modification. In this study, we have tailored and synthesized different sized mesoporous silica nanoparticles (MSNs) through reactant control to investigate the relevancy of nanoparticle size toward anticancer efficacy and suppressing cancer multidrug resistance. The different sized MSNs loaded with anticancer ruthenium complex (RuPOP) and conjugated with folate acid (FA) to enhance the selectivity between cancer and normal cells...
November 2018: Drug Delivery
https://www.readbyqxmd.com/read/29331790/c-phycocyanin-cellular-targets-mechanisms-of-action-and-multi-drug-resistance-in-cancer
#8
REVIEW
Estela Fernandes E Silva, Felipe da Silva Figueira, Aline Portantiolo Lettnin, Michele Carrett-Dias, Daza de Moraes Vaz Batista Filgueira, Susana Kalil, Gilma Santos Trindade, Ana Paula de Souza Votto
C-Phycocyanin (C-PC) has been shown to be promising in cancer treatment; however, although several articles detailing this have been published, its main mechanisms of action and its cellular targets have not yet been defined, nor has a detailed exploration been conducted of its role in the resistance of cancer cells to chemotherapy, rendering clinical use impossible. From our extensive examination of the literature, we have determined as our main hypothesis that C-PC has no one specific target, but rather acts on the membrane, cytoplasm, and nucleus with diverse mechanisms of action...
July 26, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/29331420/dacomitinib-antagonizes-multidrug-resistance-mdr-in-cancer-cells-by-inhibiting-the-efflux-activity-of-abcb1-and-abcg2-transporters
#9
Ying-Fang Fan, Wei Zhang, Leli Zeng, Zi-Ning Lei, Chao-Yun Cai, Pranav Gupta, Dong-Hua Yang, Qingbin Cui, Zuo-Dong Qin, Zhe-Sheng Chen, Louis D Trombetta
The development of multidrug resistance (MDR) to chemotherapy remains a major challenge in the treatment of cancer. Numerous mechanisms have been recognized that cause MDR, but one of the most important mechanisms is overexpression of adenosine triphosphate (ATP)-binding cassette (ABC) transporters, through which the efflux of various anticancer drugs against their concentration gradients is powered by ATP. In recent years, small molecular tyrosine kinase inhibitors (TKIs) have been developed for treatment in various human cancers overexpressing epidermal growth factor receptor (EGFR)...
January 10, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29325450/symptom-science-omics-supports-common-biological-underpinnings-across-symptoms
#10
Maura K McCall, Ansley Grimes Stanfill, Elizabeth Skrovanek, Jessica Renee Pforr, Susan W Wesmiller, Yvette P Conley
For precision health care to be successful, an in-depth understanding of the biological mechanisms for symptom development and severity is essential. Omics-based research approaches facilitate identification of the biological underpinnings of symptoms. We reviewed literature for omics-based approaches and exemplar symptoms (sleep disruption, cognitive impairment, fatigue, gastrointestinal [GI] distress, and pain) to identify genes associated with the symptom or symptoms across disease processes. The review yielded 27 genes associated with more than one symptom...
January 1, 2018: Biological Research for Nursing
https://www.readbyqxmd.com/read/29325225/influence-of-cyp2d6-cyp3a4-cyp3a5-and-abcb1-polymorphisms-on-pharmacokinetics-and-safety-of-aripiprazole-in-healthy-volunteers
#11
Carmen Belmonte, Dolores Ochoa, Manuel Román, Miriam Saiz-Rodríguez, Aneta Wojnicz, Clara Isabel Gómez-Sánchez, Samuel Martín-Vilchez, Francisco Abad-Santos
The aim of this study was to investigate the effect of polymorphisms in cytochrome P450 (CYP) 2D6, CYP3A4 and CYP3A5 enzymes and in P-glycoprotein (P-gp) on the pharmacokinetics and safety of aripiprazole and, its active metabolite, dehydro-aripiprazole, in 148 healthy volunteers from 6 bioequivalence trials receiving a single oral dose of aripiprazole. The plasma concentrations of both analytes were measured by LC-MS/MS. CYP2D6 (*3,*4,*5,*6,*7,*9 and copy number variations), CYP3A4 (*20 and *22), CYP3A5*3 and C3435T, C1236T and G2677T/A in ABCB1 gene were determined...
January 11, 2018: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29318780/the-synergistic-role-of-atp-dependent-drug-efflux-pump-and-focal-adhesion-signaling-pathways-in-vinorelbine-resistance-in-lung-cancer
#12
Takao Nakanishi, Toshi Menju, Shigeto Nishikawa, Koji Takahashi, Ryo Miyata, Kei Shikuma, Terumasa Sowa, Naoto Imamura, Masatsugu Hamaji, Hideki Motoyama, Kyoko Hijiya, Akihiro Aoyama, Toshihiko Sato, Toyofumi F Chen-Yoshikawa, Makoto Sonobe, Hiroshi Date
The vinorelbine (VRB) plus cisplatin regimen is widely used to treat non-small cell lung cancer (NSCLC), but its cure rate is poor. Drug resistance is the primary driver of chemotherapeutic failure, and the causes of resistance remain unclear. By focusing on the focal adhesion (FA) pathway, we have highlighted a signaling pathway that promotes VRB resistance in lung cancer cells. First, we established VRB-resistant (VR) lung cancer cells (NCI-H1299 and A549) and examined its transcriptional changes, protein expressions, and activations...
January 10, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29316665/towards-comprehension-of-the-abcb1-p-glycoprotein-role-in-chronic-myeloid-leukemia
#13
REVIEW
Raquel C Maia, Flavia C Vasconcelos, Paloma S Souza, Vivian M Rumjanek
Abstract: The introduction of imatinib (IM), a BCR-ABL1 tyrosine kinase inhibitor (TKI), has represented a significant advance in the first-line treatment of chronic myeloid leukemia (CML). However, approximately 30% of patients need to discontinue IM due to resistance or intolerance to this drug. Both resistance and intolerance have also been observed in treatment with the second-generation TKIs-dasatinib, nilotinib, and bosutinib-and the third-generation TKI-ponatinib. The mechanisms of resistance to TKIs may be BCR-ABL1-dependent and/or BCR-ABL1-independent...
January 7, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29314596/multiplate%C3%A2-evaluation-of-acetylsalicylic-acid-efficacy-in-carotid-surgery-routine-and-genetic-influencing-factors
#14
S Roullet, S Labrouche, C Carrie, H Auque, X Berard, G Freyburger
BACKGROUND: Acetylsalicylic acid (ASA) is recommended before, during and after carotid endarterectomy (CEA). Efficacy of ASA is influenced by numerous biological and genotypic factors. OBJECTIVES: To determine the biological efficacy of ASA by using the Multiplate® method and to explore the biological parameters and genomic factors influencing this efficacy. METHODS: This descriptive cross-sectional study included all patients scheduled for CEA between January 2012 and April 2013...
January 3, 2018: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29311482/population-pharmacokinetics-and-adverse-events-of-erlotinib-in-japanese-patients-with-non-small-cell-lung-cancer-impact-of-genetic-polymorphisms-in-metabolizing-enzymes-and-transporters
#15
Chihiro Endo-Tsukude, Ji-Ichiro Sasaki, Sho Saeki, Norihiro Iwamoto, Megumi Inaba, Sunao Ushijima, Hiroto Kishi, Shinji Fujii, Hiroshi Semba, Kosuke Kashiwabara, Yukari Tsubata, Mitsuhiro Hayashi, Yuki Kai, Hideyuki Saito, Takeshi Isobe, Hirotsugu Kohrogi, Akinobu Hamada
Determinants of interindividual variability in erlotinib pharmacokinetics (PK) and adverse events remain to be elucidated. This study with 50 Japanese non-small-cell lung cancer patients treated with oral erlotinib at a standard dose of 150 mg aimed to investigate whether genetic polymorphisms affect erlotinib PK and adverse events. Single nucleotide polymorphisms (SNPs) in genes encoding metabolizing enzymes (CYP1A1, CYP1A2, CYP2D6, CYP3A4, CYP3A5, UGT1A1, UGT2B7, GSTM1, and GSTT1) or efflux transporters (ABCB1, and ABCG2) were analyzed as covariates in a population PK model...
2018: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/29305422/tumor-stressors-induce-two-mechanisms-of-intracellular-p-glycoprotein-mediated-resistance-that-are-overcome-by-lysosomal-targeted-thiosemicarbazones
#16
Lina Al-Akra, Dong-Hun Bae, Sumit Sahni, Michael L H Huang, Kyung Chan Park, Darius J R Lane, Patric J Jansson, Des R Richardson
Multi-drug resistance (MDR) is a major obstacle in cancer treatment due to the ability of tumor cells to efflux chemotherapeutics via drug transporters e.g., P-glycoprotein (Pgp; ABCB1). While the mechanism of Pgp-mediated drug efflux is known at the plasma membrane, the functional role of intracellular Pgp is unclear. Moreover, there has been intense focus on the tumor micro-environment as a target for cancer treatment. This investigation aimed to dissect the effects of tumor micro-environmental stress on sub-cellular Pgp expression, localization and its role in MDR...
January 5, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29303075/abc-transporters-regulation-and-association-with-multidrug-resistance-in-hepatocellular-carcinoma-and-colorectal-carcinoma
#17
Maria Paula Ceballos Mancini, Juan Pablo Rigalli, Lucila Ines Cere, Mariana Semeniuk, Viviana Alicia Catania, Maria Laura Ruiz
For most cancers, the treatment of choice is still being chemotherapy despite of its severe adverse effects, systemic toxicity and limited efficacy due to the development of multidrug resistance (MDR). MDR leads to chemotherapy failure generally associated with a decrease in drug concentration inside cancer cells, frequently due to an overexpression of ABC transporters such as P-glycoprotein (P-gp/MDR1/ABCB1), multidrug resistance-associated proteins (MRPs/ABCCs), and breast cancer resistance protein (BCRP/ABCG2) that limit the efficacy of chemotherapeutic drugs...
January 4, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29299638/prediction-of-neutrophil-reduction-using-plasma-paclitaxel-concentration-after-administration-in-patients-with-uterine-ovarian-or-cervical-cancers-in-an-outpatient-clinic
#18
Motoaki Ishikawa, Michiyasu Kawai, Toshio Maeda, Yoshiyuki Kagawa
PURPOSE: Plasma paclitaxel (PTX) concentration 24 h or later after PTX administration may predict myelosuppression. Here, we explored predictive markers for neutropenia induced by intravenous administration of PTX in an outpatient clinic. METHODS: Thirty women suffering from uterine, ovarian or cervical cancer were enrolled in this study. PTX (mean dose: 167 mg/m2) was intravenously infused and followed by carboplatin. Plasma samples were obtained 4 h after PTX administration...
January 3, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29286612/unexpected-lower-expression-of-oncoprotein-gankyrin-in-drug-resistant-abcg2-overexpressing-breast-cancer-cell-lines
#19
Taheri Taheri, Khadijeh Jamialahmadi, Fatemeh Khadijeh
Background: Development of a multidrug resistance (MDR) phenotype to chemotherapy remains a major barrier in the treatment of cancer. Gankyrin (p28, p28GANK or PSMD10) is an oncoprotein overexpressed in different carcinoma cell lines. The aim of this study was to compare Gankyrin expression level in MDR cells (MCF-7/ADR and MCF-7/ MX) and non-MDR counterparts (MCF-7). Methods: Gankyrin, MDR1 (also known as ABCB1; the ATP-binding cassette sub-family B member 1) and ABCG2 (also known as BCRP; the human breast cancer resistance protein) mRNA levels were analyzed by real-time RT-PCR...
December 29, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/29285232/synergistic-effect-of-farnesyl-transferase-inhibitor-lonafarnib-combined-with-chemotherapeutic-agents-against-the-growth-of-hepatocellular-carcinoma-cells
#20
Jialiang Wang, Yifan Lian, Yurong Gu, Hongbo Wang, Lin Gu, Yanlin Huang, Liang Zhou, Yuehua Huang
Hepatocellular carcinoma (HCC) is a common and deadly cancer worldwide and is often refractory to chemotherapy due to the development of multidrug resistance. Lonafarnib is an orally active and potent non-peptidomimetic inhibitor of farnesyl transferase. Here, using in vitro HCC cell models, we demonstrated that lonafarnib inhibited tumor proliferation and reduced the activity of mitogen-activated protein kinases pathways. In addition, lonafarnib caused G1 to S phase arrest through the downregulation of Cyclin D1, CDK6 and SKP2, while it induced cellular apoptosis by promoting the cleavage and activation of Caspase-3 and PARP...
December 1, 2017: Oncotarget
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