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https://www.readbyqxmd.com/read/28339912/pharmacogenomics-and-patient-treatment-parameters-to-opioid-treatment-in-chronic-pain-a-focus-on-morphine-oxycodone-tramadol-and-fentanyl
#1
Renae A Lloyd, Elizabeth Hotham, Catherine Hall, Marie Williams, Vijayaprakash Suppiah
Objective. : Opioids are one of the most commonly prescribed medicines for chronic pain. However, their use for chronic pain has been controversial. The objective of this literature review was to identify the role of genetic polymorphisms on patient treatment parameters (opioid dose requirements, response, and adverse effects) for opioids used in malignant and nonmalignant chronic pain. The opioids that this review focuses on are codeine, morphine, oxycodone, tramadol, and fentanyl...
February 24, 2017: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
https://www.readbyqxmd.com/read/28335376/genetic-polymorphisms-contribute-to-the-individual-variations-of-imatinib-mesylate-plasma-levels-and-adverse-reactions-in-chinese-gist-patients
#2
Jing Liu, Zhiyu Chen, Hanmei Chen, Yingyong Hou, Weiqi Lu, Junyi He, Hanxing Tong, Yuhong Zhou, Weimin Cai
Imatinib mesylate (IM) has dramatically improved the outcomes of gastrointestinal stromal tumor (GIST) patients. However, the clinical responses of IM may considerably vary among single individuals. This study aimed to investigate the influences of genetic polymorphisms of drug-metabolizing enzyme (CYP3A4), transporters (ABCB1, ABCG2), and nuclear receptor (Pregnane X Receptor (PXR, encoded by NR1I2)) on IM plasma levels and related adverse reactions in Chinese GIST patients. A total of 68 Chinese GIST patients who have received IM 300-600 mg/day were genotyped for six single nucleotide polymorphisms (SNPs) (CYP3A4 rs2242480; ABCB1 rs1045642; ABCG2 rs2231137; NRI12 rs3814055, rs6785049, rs2276706), and the steady-state IM trough plasma concentrations were measured by a validated HPLC method...
March 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28329446/in-vitro-intrinsic-permeability-a-transporter-independent-measure-of-caco-2-cell-permeability-in-drug-design-and-development
#3
Linda Fredlund, Susanne Winiwarter, Constanze Hilgendorf
In-vitro permeability data have a central place in absorption risk assessments in drug discovery and development. For compounds where active efflux impacts permeability in vitro, the inherent passive membrane permeability ("intrinsic permeability"), gives a concentration-independent measure of the compound's permeability. This work describes the validation of an in-vitro intrinsic permeability assay and application of the data in a predictive in-silico model. Apparent intrinsic permeability (Papp) across Caco-2 cell monolayers is determined in presence of an optimized cocktail of chemical inhibitors towards the three major efflux transporters ABCB1, ABCC2, and ABCG2...
March 22, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28324194/sex-differences-in-the-blood-concentration-of-tacrolimus-in-systemic-lupus-erythematosus-and-rheumatoid-arthritis-patients-with-cyp3a5-3-3
#4
Ayano Ito, Yuko Okada, Tadahiro Hashita, Tohru Aomori, Keiju Hiromura, Yoshihisa Nojima, Tomonori Nakamura, Takuya Araki, Koujirou Yamamoto
The purpose of this study was to describe the impact of sex and cytochrome P450 3A5 (CYP3A5) variant on the blood concentration of tacrolimus in patients with systemic lupus erythematosus or rheumatoid arthritis. The blood concentration of tacrolimus (ng/mL) divided by the daily dose of tacrolimus (mg/day) and the patient's weight (kg) (C/D) was obtained from 55 patients. The C/D value was analysed according to genetic variation in CYP3A5 or ATP binding cassette subfamily B member 1 (ABCB1), sex, and age. The C/D value in the CYP3A5*3/*3 group was significantly higher than in the CYP3A5*1/*1 and *1/*3 groups (p < 0...
March 21, 2017: Biochemical Genetics
https://www.readbyqxmd.com/read/28323030/antisense-lncrna-foxc2-as1-promotes-doxorubicin-resistance-in-osteosarcoma-by-increasing-the-expression-of-foxc2
#5
Zhang Chun-Lin, Zhu Kun-Peng, Ma Xiao-Long
Recent efforts have revealed that numerous natural antisense lncRNAs play a crucial role in the regulation of cancer biology. Here, based on our previous study, we further identified that the lncRNA FOXC2-AS1 and its antisense transcript FOXC2 were positively up-regulated in doxorubicin-resistant osteosarcoma cell lines and tissues, correlate with poor prognosis and promote doxorubicin resistance in osteosarcoma cells in vitro and in vivo. In addition, FOXC2-AS1 and FOXC2 are mainly located in the cytoplasm and form an RNA-RNA double-stranded structure in the overlapping region, which is necessary for FOXC2-AS1 to regulate the expression of FOXC2 at both the transcription and post-transcription levels...
March 16, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28321153/p-glycoprotein-multidrug-transporter-in-inflammatory-bowel-diseases-more-questions-than-answers
#6
EDITORIAL
Elke Cario
The gastrointestinal barrier is constantly exposed to numerous environmental substrates that are foreign and potentially harmful. These xenobiotics can cause shifts in the intestinal microbiota composition, affect mucosal immune responses, disturb tissue integrity and impair regeneration. The multidrug transporter ABCB1/MDR1 p-glycoprotein (p-gp) plays a key role at the front line of host defence by efficiently protecting the gastrointestinal barrier from xenobiotic accumulation. This Editorial discusses how altered expression and function of ABCB1/MDR1 p-gp may contribute to the development and persistence of chronic intestinal inflammation in inflammatory bowel diseases (IBD)...
March 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28321040/whole-exome-sequencing-detects-variants-of-genes-that-mediate-response-to-anticancer-drugs
#7
Sumiko Ohnami, Takeshi Nagashima, Kenichi Urakami, Yuji Shimoda, Fukumi Kamada, Junko Saito, Akane Naruoka, Masakuni Serizawa, Yoko Masuda, Shumpei Ohnami, Masatoshi Kusuhara, Ken Yamaguchi
Certain interindividual differences affecting the efficacy of drug treatment and adverse drug reactions are caused by genetic variants, and their phenotypic effects differ among ethnic groups. In this study, we used whole exome sequencing (WES) systematically to identify germline mutations that influence the activities of drug-metabolizing enzymes, as well as that of a transporter. We analyzed DNA isolated from blood samples from 2,042 Japanese patients with diverse cancers. We identified sequence variants of CYP2B6 (rs3745274), CYP2C9 (rs1057910), CYP2C19 (rs4986893), CYP2C19 (rs4244285), TPMT (rs1142345), NAT2 (rs1799930), NAT2 (rs1799931), UGT1A1 (rs4148323), COMT (rs4680), ABCB1 (rs1045642), and CDA (rs60369023)...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28320034/variations-in-infant-cyp2b6-genotype-associated-with-the-need-for-pharmacological-treatment-for-neonatal-abstinence-syndrome-in-infants-of-methadone-maintained-opioid-dependent-mothers
#8
Helen Mactier, Poppy McLaughlin, Cheryl Gillis, Michael David Osselton
Background Neonatal abstinence syndrome (NAS) in infants of methadone-maintained opioid-dependent (MMOD) mothers cannot be predicted in individual cases. We investigated whether variation in infant genotype is associated with severity of NAS. Methods This is a pilot observational cohort study of 21 MMOD mothers and their newborns. Infant buccal swabs were obtained soon after delivery, together with a maternal blood sample for the determination of maternal plasma methadone concentration. Genomic variation in five opioid-related genes (ABCB1, COMT, CYP2B6, CYP2D6, and OPRM1) was ascertained from infant buccal swabs and related to need for pharmacological treatment of NAS...
March 20, 2017: American Journal of Perinatology
https://www.readbyqxmd.com/read/28318792/halogen-free-organophosphorus-flame-retardants-caused-oxidative-stress-and-multixenobiotic-resistance-in-asian-freshwater-clams-corbicula-fluminea
#9
Saihong Yan, Huimin Wu, Jianhui Qin, Jinmiao Zha, Zijian Wang
Halogen-free organophosphorus flame retardants are widespread in aquatic environments. Although it has been documented that they affect the behavior and reproduction of aquatic species, researches investigating cellular detoxification and the defense system in bivalves are scarce. In this study, adult Asian clams (C. fluminea) were exposed to tris (2-butoxyethyl) phosphate (TBEP) and tributyl phosphate (TBP) at 20, 200, and 2000 μg/L for 28 d. The results showed no noticeable difference in siphoning behavior...
March 16, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28303314/-genetic-tests-for-controlling-treatment-with-antidepressants
#10
T Bschor, C Baethge, C Hiemke, B Müller-Oerlinghausen
In clinical practice, there is a need for a more individualized selection of antidepressants and adequate dosage. The investigation of pharmacokinetically relevant genes is a promising approach to assist this selection. In the past 2 years, two commercially available tests have been subject of advertisement, a test from Stada, which analyses variants of the cytochrome P450 isoenzymes CYP2D6 and CYP2C19 and a test from HMNC Brain Health, which analyses variants of the ABCB1 gene. The costs for both kits are not covered by the statutory health insurance and it is therefore proposed that the patients are invoiced directly in the form of individual healthcare payment...
March 16, 2017: Der Nervenarzt
https://www.readbyqxmd.com/read/28303028/alectinib-ch5424802-antagonizes-abcb1-and-abcg2-mediated-multidrug-resistance-in-vitro-in-vivo-and-ex-vivo
#11
Ke Yang, Yifan Chen, Kenneth Kin Wah To, Fang Wang, Delan Li, Likun Chen, Liwu Fu
Alectinib, an inhibitor of anaplastic lymphoma kinase (ALK), was approved by the Food and Drug Administration (FDA) for the treatment of patients with ALK-positive non-small cell lung cancer (NSCLC). Here we investigated the reversal effect of alectinib on multidrug resistance (MDR) induced by ATP-binding cassette (ABC) transporters, which is the primary cause of chemotherapy failure. We provide the first evidence that alectinib increases the sensitivity of ABCB1- and ABCG2-overexpressing cells to chemotherapeutic agents in vitro and in vivo...
March 17, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28302530/regorafenib-overcomes-chemotherapeutic-multidrug-resistance-mediated-by-abcb1-transporter-in-colorectal-cancer-in-vitro-and-in-vivo-study
#12
Yi-Jun Wang, Yun-Kai Zhang, Guan-Nan Zhang, Sweilem B Al Rihani, Meng-Ning Wei, Pranav Gupta, Xiao-Yu Zhang, Suneet Shukla, Suresh V Ambudkar, Amal Kaddoumi, Zhi Shi, Zhe-Sheng Chen
Chemotherapeutic multidrug resistance (MDR) is a significant challenge to overcome in clinic practice. Several mechanisms contribute to MDR, one of which is the augmented drug efflux induced by the upregulation of ABCB1 in cancer cells. Regorafenib, a multikinase inhibitor targeting the RAS/RAF/MEK/ERK pathway, was approved by the FDA to treat metastatic colorectal cancer and gastrointestinal stromal tumors. We investigated whether and how regorafenib overcame MDR mediated by ABCB1. The results showed that regorafenib reversed the ABCB1-mediated MDR and increased the accumulation of [(3)H]-paclitaxel in ABCB1-overexpressing cells by suppressing efflux activity of ABCB1, but not altering expression level and localization of ABCB1...
March 13, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28301155/exploration-of-2-pyridin-4-ylmethyl-amino-nicotinamide-derivatives-as-potent-reversal-agents-against-p-glycoprotein-mediated-multidrug-resistance
#13
Qianqian Qiu, Wei Shi, Zheng Li, Bo Zhang, Miaobo Pan, Jian Cui, Yuxuan Dai, Wenlong Huang, Hai Qian
Overexpression of the ATP-binding cassette (ABC) transport proteins, like ABCB1, commonly referred to as P-glycoprotein (P-gp), initiates active efflux of a broad spectrum of unrelated chemotherapeutic drugs in structure and function, leading to chemotherapy failure. A series of 2-((pyridin-4-ylmethyl)amino)nicotinamide derivatives as potent reversal agents against P-glycoprotein-mediated multidrug resistance (MDR) were designed and synthesized. The majority of target compounds displayed great reversal potency, especially 9n...
March 16, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28299396/no-correlation-between-mthfr-c-677-c%C3%A2-%C3%A2-t-mthfr-c-1298-a%C3%A2-%C3%A2-c-and-abcb1-c-3435-c%C3%A2-%C3%A2-t-polymorphisms-and-methotrexate-therapeutic-outcome-of-rheumatoid-arthritis-in-west-algerian-population
#14
Wefa Boughrara, Ahmed Benzaoui, Meriem Aberkane, Fatima Zohra Moghtit, Samia Dorgham, Aicha Sarah Lardjam-Hetraf, Hadjer Ouhaibi-Djellouli, Elisabeth Petit Teixeira, Abdallah Boudjema
CONTEXT: The c.677 C > T and c.1298 A > C polymorphisms of methylenetatrahydrofolate reductase (MTHFR) gene and c.3435 C > T polymorphism of ATP-Binding cassette B1 (ABCB1) gene are reported as pharmacogenetic markers, influencing the methotrexate (MTX) therapeutic outcome in rheumatoid arthritis (RA) patients. OBJECTIVES: The aims of this study were to determine the relationship between these polymorphisms and clinical response and/or adverse drug reaction (ADRs) to MTX treatment...
March 15, 2017: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/28295025/glycol-porphyrin-derivatives-and-temoporfin-elicit-resistance-to-photodynamic-therapy-by-different-mechanisms
#15
Jarmila Kralova, Michal Kolar, Michal Kahle, Jaroslav Truksa, Sandra Lettlova, Kamila Balusikova, Petr Bartunek
The development of drug resistance is a major problem which often occurs during anticancer chemotherapies. Photodynamic therapy (PDT) has been studied as an alternative treatment modality for drug-resistant tumors, however the question of resistance to PDT and potential cross-resistance with chemotherapy has yet to be fully answered. To investigate the mechanism of resistance to PDT, we developed an in vitro experimental model system in a mouse mammary carcinoma cell line 4T1. We used two ethylene glycol derivatives of tetraphenylporphyrin, and tetraphenylchlorin derivative, temoporfin, as photosensitizers (PS)...
March 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28293855/growth-hormone-receptor-knockdown-sensitizes-human-melanoma-cells-to-chemotherapy-by-attenuating-expression-of-abc-drug-efflux-pumps
#16
Reetobrata Basu, Nicholas Baumgaertel, Shiyong Wu, John J Kopchick
Melanoma remains one of the most therapy-resistant forms of human cancer despite recent introductions of highly efficacious targeted therapies. The intrinsic therapy resistance of human melanoma is largely due to abundant expression of a repertoire of xenobiotic efflux pumps of the ATP-binding cassette (ABC) transporter family. Here, we report that GH action is a key mediator of chemotherapeutic resistance in human melanoma cells. We investigated multiple ABC efflux pumps (ABCB1, ABCB5, ABCB8, ABCC1, ABCC2, ABCG1, and ABCG2) reportedly associated with melanoma drug resistance in different human melanoma cells and tested the efficacy of five different anti-cancer compounds (cisplatin, doxorubicin, oridonin, paclitaxel, vemurafenib) with decreased GH action...
March 14, 2017: Hormones & Cancer
https://www.readbyqxmd.com/read/28291260/gene-expression-and-proliferation-biomarkers-for-antidepressant-treatment-resistance
#17
J Breitfeld, C Scholl, M Steffens, G Laje, J C Stingl
The neurotrophic hypothesis of depression suggests an association between effects on neuroplasticity and clinical response to antidepressant drug therapy. We studied individual variability in antidepressant drug effects on cell proliferation in lymphoblastoid cell lines (LCLs) from n=25 therapy-resistant patients versus n=25 first-line therapy responders from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Furthermore, the variability in gene expression of genes associated with cell proliferation was analyzed for tentative candidate genes for prediction of individual LCL donor's treatment response...
March 14, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28289867/association-of-the-hoct1-abcb1-genotype-with-efficacy-and-tolerability-of-imatinib-in-patients-affected-by-chronic-myeloid-leukemia
#18
Laura Galeotti, Francesco Ceccherini, Dario Domingo, Marco Laurino, Marialuisa Polillo, Antonello Di Paolo, Claudia Baratè, Carmen Fava, Antonio D'Avolio, Giulia Cervetti, Francesca Guerrini, Giulia Fontanelli, Elena Ciabatti, Susanna Grassi, Elena Arrigoni, Romano Danesi, Mario Petrini, Fulvio Cornolti, Giuseppe Saglio, Sara Galimberti
PURPOSE: The present study was aimed at investigating whether imatinib pharmacogenetics is related to its pharmacodynamics in patients affected by chronic myeloid leukemia. METHODS: Through a procedure based on a sequence of classical statistics methods, we investigated the possible relationships between treatment efficacy/tolerability and combinations of time-independent variables as gender and genetic covariates in the form of single nucleotide polymorphisms (SNPs) or combinations thereof...
March 13, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28289864/correlation-between-clinical-response-to-sorafenib-in-hepatocellular-carcinoma-treatment-and-polymorphisms-of-p-glycoprotein-abcb1-and-of-breast-cancer-resistance-protein-abcg2-monocentric-study
#19
Mahamadou Tandia, Asma Mhiri, Bernard Paule, Raphaël Saffroy, Valérie Cailliez, Gaëlle Noé, Robert Farinotti, Laurence Bonhomme-Faivre
OBJECTIVES: We studied the relation between the polymorphism of P-glycoprotein (P-gp) and of breast cancer resistance protein (BCRP), encoded by ABCB1 and ABCG2 genes, respectively, and the pharmacokinetic variability and clinical response during the treatment with sorafenib of hepatocellular carcinoma. METHODS: At the Paul Brousse Hospital in Villejuif, France, 47 consecutive patients with advanced HCC treated with a single agent sorafenib, were enrolled. Sorafenib exposure was measured by its plasma concentration 3 h after oral administration of 400 mg (bid) by liquid chromatography...
March 13, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28289287/energy-transduction-and-alternating-access-of-the-mammalian-abc-transporter-p-glycoprotein
#20
Brandy Verhalen, Reza Dastvan, Sundarapandian Thangapandian, Yelena Peskova, Hanane A Koteiche, Robert K Nakamoto, Emad Tajkhorshid, Hassane S Mchaourab
ATP binding cassette (ABC) transporters of the exporter class harness the energy of ATP hydrolysis in the nucleotide-binding domains (NBDs) to power the energetically uphill efflux of substrates by a dedicated transmembrane domain (TMD). Although numerous investigations have described the mechanism of ATP hydrolysis and defined the architecture of ABC exporters, a detailed structural dynamic understanding of the transduction of ATP energy to the work of substrate translocation remains elusive. Here we used double electron-electron resonance and molecular dynamics simulations to describe the ATP- and substrate-coupled conformational cycle of the mouse ABC efflux transporter P-glycoprotein (Pgp; also known as ABCB1), which has a central role in the clearance of xenobiotics and in cancer resistance to chemotherapy...
March 13, 2017: Nature
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