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https://www.readbyqxmd.com/read/27909344/response-to-overexpression-of-abcb1-as-prediction-marker-for-cml-how-close-we-are-to-translation-into-clinics
#1
L N Eadie, T P Hughes, D L White
No abstract text is available yet for this article.
December 2, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27908290/bile-acid-a-potential-inducer-of-colon-cancer-stem-cells
#2
Lulu Farhana, Pratima Nangia-Makker, Evan Arbit, Kathren Shango, Sarah Sarkar, Hamidah Mahmud, Timothy Hadden, Yingjie Yu, Adhip P N Majumdar
BACKGROUND: Although the unconjugated secondary bile acids, specifically deoxycholic acid (DCA) and lithocholic acid (LCA), are considered to be risk factors for colorectal cancer, the precise mechanism(s) by which they regulate carcinogenesis is poorly understood. We hypothesize that the cytotoxic bile acids may promote stemness in colonic epithelial cells leading to generation of cancer stem cells (CSCs) that play a role in the development and progression of colon cancer. METHODS: Normal human colonic epithelial cells (HCoEpiC) were used to study bile acid DCA/LCA-mediated induction of CSCs...
December 1, 2016: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/27906699/reversal-effects-of-local-anesthetics-on-p-glycoprotein-mediated-cancer-multidrug-resistance
#3
Yong Hu, Xiaobing Qin, Haixia Cao, Shaorong Yu, Jifeng Feng
The existence of multidrug resistance (MDR) is the main reason for failure in cancer chemotherapy. The main mechanism of MDR is the overexpression of P-glycoprotein (P-gp). P-gp, a 170 kDa transmembrane phosphorylated glycoprotein encoded by ABCB1 belonging to a member of the ATP-binding cassette (ABC) super-family of the membrane transporters, is also known as the MDR protein. Local anesthetics (LAs) are a major contributor to medical practice. As a cornerstone of analgesia, LAs provides myriad benefits...
November 30, 2016: Anti-cancer Drugs
https://www.readbyqxmd.com/read/27897269/an-integrated-pharmacokinetic-pharmacogenomic-analysis-of-abcb1-and-slco1b1-polymorphisms-on-edoxaban-exposure
#4
A G Vandell, J Lee, M Shi, I Rubets, K S Brown, J R Walker
Edoxaban and its low-abundance, active metabolite M4 are substrates of P-glycoprotein (P-gp; MDR1) and organic anion transporter protein 1B1 (OATP1B1), respectively, and pharmacological inhibitors of P-gp and OATP1B1 can affect edoxaban and M4 pharmacokinetics (PK). In this integrated pharmacogenomic analysis, genotype and concentration-time data from 458 healthy volunteers in 14 completed phase 1 studies were pooled to examine the impact on edoxaban PK parameters of allelic variants of ABCB1 (rs1045642: C3435T) and SLCO1B1 (rs4149056: T521C), which encode for P-gp and OATP1B1...
November 29, 2016: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/27897267/increasing-bmi-is-associated-with-reduced-expression-of-p-glycoprotein-abcb1-gene-in-the-human-brain-with-a-stronger-association-in-african-americans-than-caucasians
#5
J Vendelbo, R H Olesen, J K Lauridsen, J Rungby, J E Kleinman, T M Hyde, A Larsen
The efflux pump, p-glycoprotein, controls bioavailability and excretion of pharmaceutical compounds. In the blood-brain barrier, p-glycoprotein regulates the delivery of pharmaceutical substances to the brain, influencing efficacy and side effects for some drugs notably antipsychotics. Common side effects to antipsychotics include obesity and metabolic disease. Polymorphisms in the ABCB1 gene coding for p-glycoprotein are associated with more severe side effects to neuro-pharmaceuticals as well as weight gain, indicating a potential link between p-glycoprotein function and metabolic regulation...
November 29, 2016: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/27895309/hepatocyte-specific-expression-of-an-oncogenic-variant-of-%C3%AE-catenin-results-in-cholestatic-liver-disease
#6
Ursula J Lemberger, Claudia Fuchs, Matthias Karer, Stefanie Haas, Tatjana Stojakovic, Christian Schöfer, Hanns-Ulrich Marschall, Fritz Wrba, Makoto M Taketo, Gerda Egger, Michael Trauner, Christoph H Österreicher
BACKGROUND: The Wnt/β-catenin signaling pathway plays a crucial role in embryonic development, tissue homeostasis, wound healing and malignant transformation in different organs including the liver. The consequences of continuous β-catenin signaling in hepatocytes remain elusive. RESULTS: Livers of Ctnnb1CA hep mice were characterized by disturbed liver architecture, proliferating cholangiocytes and biliary type of fibrosis. Serum ALT and bile acid levels were significantly increased in Ctnnb1CA hep mice...
November 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27893429/microrna-595-sensitizes-ovarian-cancer-cells-to-cisplatin-by-targeting-abcb1
#7
Songyu Tian, Mingyue Zhang, Xiuwei Chen, Yunduo Liu, Ge Lou
Ovarian cancer is among the leading cause of cancer-related deaths in females. In this study, we demonstrated that miR-595 expression was downregulated in the ovarian cancer tissues and cell lines. miR-595 expression was lower in the lymph node metastases tissues than in the primary ovarian cancer tissues and normal tissues. Furthermore, miR-595 overexpression suppressed the ovarian cancer cell proliferation, colony formation and invasion and promoted the sensitivity of ovarian cancer cell to cisplatin. We identified ABCB1 as a direct target gene of miR-595 in the ovarian cancer cell...
November 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27893182/inter-individual-variability-in-dabigatran-and-rivaroxaban-exposure-contribution-of-abcb1-genetic-polymorphisms-and-interaction-with-clarithromycin
#8
I Gouin-Thibault, X Delavenne, A Blanchard, V Siguret, J E Salem, C Narjoz, P Gaussem, P Beaune, C Funck-Brentano, M Azizi, P Mismetti, M A Loriot
BACKGROUND: The direct oral anticoagulants (DOACs) dabigatran and rivaroxaban are both substrates of the P-glycoprotein (P-gp) transporter, encoded by the ABCB1 gene. Rivaroxaban is metabolized by CYP3A4. Inter-individual variability in DOAC exposure and frequent P-gp associated drug-drug interactions have been described in patients. OBJECTIVE: To assess the influence of ABCB1 polymorphisms on the pharmacokinetics (PK) of dabigatran and rivaroxaban, associated or not with clarithromycin, a P-gp and CYP3A4 inhibitor...
November 28, 2016: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/27889704/pharmacogenetic-studies-a-tool-to-improve-antidepressant-therapy
#9
Marta Ramos, Cecilia Berrogain, Julia Concha, Laura Lomba, Cristina Belén García, Mª Pilar Ribate
The World Health Organization (WHO) predicts that major depressive disorder (MDD) will be the second leading cause of death and disability by 2020. Nowadays, approximately 60-70% of patients with this disorder have shown the lack of effectiveness and tolerability of the therapy with antidepressants. The US Food and Drug Administration (FDA) and the European Medicine Agency (EMA) are including pharmacogenetic information in the labeling of several antidepressants. The presence of this information represents the relevance of genetic polymorphisms in drug response...
December 1, 2016: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/27888070/phosphoramide-mustard-induces-autophagy-markers-and-mtor-inhibition-prevents-follicle-loss-due-to-phosphoramide-mustard-exposure
#10
Jill A Madden, Porsha Q Thomas, Aileen F Keating
Phosphoramide mustard (PM) is an ovotoxic metabolite of cyclophosphamide. Postnatal day 4 Fisher 344 rat ovaries were exposed to vehicle control (1% DMSO) or PM (60μM) ± LY294002 or rapamycin for 2 or 4 d. Transmission election microscopy revealed abnormally large golgi apparatus and electron dense mitochondria in PM-exposed ovaries prior to and at the time of follicle depletion. PM exposure increased (P<0.05) mRNA abundance of Bbc3, Cdkn1a, Ctfr, Edn1, Gstp1, Nqo1, Tlr4, Tnfrsfla, Txnrd1 and decreased (P<0...
November 22, 2016: Reproductive Toxicology
https://www.readbyqxmd.com/read/27886333/association-between-the-polymorphisms-in-the-atp-binding-cassette-genes-abcb1-and-abcc2-and-the-risk-of-drug-resistant-epilepsy-in-a-chinese-han-population
#11
T Xue, Z N Lu
Epilepsy is a common disease of the nervous system; approximately 20-30% of all patients with epilepsy are reported resistant to antiepileptic drugs. ABCB1 and ABCC2 are members of ATP-binding cassette transporter (ABC) family that is involved in the excretion of antiepileptic drugs. In this case-control study, we have investigated the role of ABCB1 rs1045642 and rs2032582 and ABCC2 rs2273697 and rs717620 single nucleotide polymorphisms in antiepileptic drug-resistance in patients with epilepsy. A total of 254 patients with epilepsy (104 drug-resistant and 150 drug-responsive) were recruited from the People's Hospital of Wuhan University between March 2013 and April 2014...
November 25, 2016: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/27883323/association-of-single-nucleotide-polymorhism-c3435t-in-the-abcb1-gene-with-opioid-sensitivity-in-treatment-of-postoperative-pain
#12
Vanja Dzambazovska-Trajkovska, Jordan Nojkov, Andrijan Kartalov, Biljana Kuzmanovska, Tatjana Spiroska, Redzep Seljmani, Gjorgji Trajkovski, Nadica Matevska-Geshkovska, Aleksandar Dimovski
BACKGROUND: The minimal effective analgesic concentration of opioids required for satisfactory analgesia may differ significantly among the patients. Genetic factors may contribute to the variable response to opioids by affecting their pharmacokinetics or pharmacodynamics. METHODS: Ninety nine patients undergoing abdominal surgery with colorectal anastomosis because of colorectal carcinoma were enrolled in the present study. C34535T was genotyped in all subjects and the patients were divided into three groups according to their genotype: CC-wild type homozygous, CT-mutant heterozygous and TT-mutant homozygous...
November 1, 2016: Prilozi (Makedonska Akademija Na Naukite i Umetnostite. Oddelenie za Medicinski Nauki)
https://www.readbyqxmd.com/read/27872246/shade-avoidance-4-is-required-for-proper-auxin-distribution-in-the-hypocotyl
#13
Yanhua Ge, Fenglian Yan, Melina Zourelidou, Meiling Wang, Karin Ljung, Astrid Fastner, Ulrich Zeno Hammes, Martin di Donato, Markus Geisler, Claus Schwechheimer, Yi Tao
The phytohormone auxin is involved in virtually every aspect of plant growth and development. Through polar auxin transport, auxin gradients can be established, which then direct plant differentiation and growth. Shade avoidance responses are well-known processes that require polar auxin transport. Here, we have identified a sav4 (shade avoidance 4) mutant that is defective in shade-induced hypocotyl elongation and basipetal auxin transport. SAV4 encodes an unknown protein with armadillo (ARM) repeat- and tetratricopeptide repeat (TPR)-like domains known to provide protein-protein interaction surfaces...
November 21, 2016: Plant Physiology
https://www.readbyqxmd.com/read/27871908/acetylated-deoxycholic-dca-and-cholic-ca-acids-are-potent-ligands-of-pregnane-x-pxr-receptor
#14
Alejandro Carazo, Lucie Hyrsova, Jan Dusek, Hana Chodounska, Alzbeta Horvatova, Karel Berka, Vaclav Bazgier, Hongying Gan-Schreier, Waleé Chamulitrat, Eva Kudova, Petr Pavek
The Pregnane X (PXR), Vitamin D (VDR) and Farnesoid X (FXR) nuclear receptors have been shown to be receptors of bile acids controlling their detoxification or synthesis. Chenodeoxycholic (CDCA) and lithocholic (LCA) acids are ligands of FXR and VDR, respectively, whereas 3-keto and acetylated derivates of LCA have been described as ligands for all three receptors. In this study, we hypothesized that oxidation or acetylation at position 3, 7 and 12 of bile acids DCA (deoxycholic acid), LCA, CA (cholic acid), and CDCA by detoxification enzymes or microbiome may have an effect on the interactions with bile acid nuclear receptors...
November 18, 2016: Toxicology Letters
https://www.readbyqxmd.com/read/27866817/discovery-of-novel-n-phenyl-1-4-dihydropyridines-with-a-dual-mode-of-antimycobacterial-activity
#15
Fabian Lentz, Marc Hemmer, Norbert Reiling, Andreas Hilgeroth
There is an urgent need for novel drugs for the treatment of tuberculosis (TB) due to the increasing prevalence of antibiotic resistance among Mycobacterium tuberculosis (Mtb) strains against first-line and second-line therapeutics. We developed novel N-phenyl 1,4-dihydropyridines as potential antituberculotic agents. The observed activity depends on the substitution patterns of the aromatic residues. N-unsubstituted 1,4-dihydropyridines are known inhibitors of the cancer-relevant transmembrane efflux pump ABCB1...
December 15, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27861472/-rheumatoid-arthritis-ra-disease-activity-predicts-function-of-abcb1-p-gp-and-abcg2-bcrp1-drug-efflux-transporters
#16
Virginia Pascual-Ramos, Yemil Atisha-Fregoso, Guadalupe Lima, Hilda Fragoso-Loyo, Juan Jákez-Ocampo, Irazú Contreras-Yáñez, Luis Llorente
BACKGROUND: P-gp and BCRP1 are transporter proteins that may confer drug resistance. OBJECTIVE: To compare P-gp and BCRP1 function in rheumatoid arthritis patients with active and inactive disease and to define their relation with disease activity. METHODS: We included 17 active patients paired (age, gender, disease duration) to 17 inactive patients. All had baseline evaluations and 27 had additional six-month follow-up. P-gp and BCRP1 functional activity was measured in peripheral mononuclear cells by flow cytometry...
November 2016: Gaceta Médica de México
https://www.readbyqxmd.com/read/27858847/drug-related-genetic-polymorphisms-affecting-severe-chemotherapy-induced-neutropenia-in-breast-cancer-patients-a-hospital-based-observational-study
#17
Daiki Tsuji, Midori Ikeda, Keisuke Yamamoto, Harumi Nakamori, Yong-Il Kim, Yohei Kawasaki, Aki Otake, Mari Yokoi, Kazuyuki Inoue, Keita Hirai, Hidenori Nakamichi, Umi Tokou, Mitsuru Shiokawa, Kunihiko Itoh
Chemotherapy-induced neutropenia (CIN) is one of the major adverse events that necessitate chemotherapy dose reduction. This study aimed to evaluate the association between grade 4 neutropenia and genetic polymorphisms in breast cancer patients. In this genetic polymorphism association study, peripheral blood samples from 100 consecutive breast cancer outpatients, between August 2012 and September 2014, treated with doxorubicin and cyclophosphamide (AC) combination chemotherapy were genotyped for polymorphisms in adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1), cytochrome P450 (CYP) enzyme-coding genes (CYP2B6 and CYP3A5), glutathione S-transferase (GST), and excision repair cross-complementing 1 (ERCC1)...
November 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27845776/proliferation-rates-and-gene-expression-profiles-in-human-lymphoblastoid-cell-lines-from-patients-with-depression-characterized-in-response-to-antidepressant-drug-therapy
#18
J Breitfeld, C Scholl, M Steffens, K Brandenburg, K Probst-Schendzielorz, O Efimkina, D Gurwitz, M Ising, F Holsboer, S Lucae, J C Stingl
The current therapy success of depressive disorders remains in need of improvement due to low response rates and a delay in symptomatic improvement. Reliable functional biomarkers would be necessary to predict the individual treatment outcome. On the basis of the neurotrophic hypothesis of antidepressant's action, effects of antidepressant drugs on proliferation may serve as tentative individual markers for treatment efficacy. We studied individual differences in antidepressant drug effects on cell proliferation and gene expression in lymphoblastoid cell lines (LCLs) derived from patients treated for depression with documented clinical treatment outcome...
November 15, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27845419/abc-transporter-polymorphisms-are-associated-with-irinotecan-pharmacokinetics-and-neutropenia
#19
M Li, E L Seiser, R M Baldwin, J Ramirez, M J Ratain, F Innocenti, D L Kroetz
Neutropenia is a common dose-limiting toxicity associated with irinotecan treatment. Although UGT1A1 variants have been associated with neutropenia, a fraction of neutropenia risk remains unaccounted for. To identify additional genetic markers contributing to variability in irinotecan pharmacokinetics and neutropenia, a regression analysis was performed in 78 irinotecan-treated patients to analyze comprehensively three hepatic efflux transporter genes (ABCB1, ABCC1 and ABCG2). rs6498588 (ABCC1) and rs12720066 (ABCB1) were associated with increased SN-38 exposure, and rs17501331 (ABCC1) and rs12720066 were associated with lower absolute neutrophil count nadir...
November 15, 2016: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/27835872/targeting-abcb1-mdr1-in-multi-drug-resistant-osteosarcoma-cells-using-the-crispr-cas9-system-to-reverse-drug-resistance
#20
Tang Liu, Zhihong Li, Qing Zhang, Karen De Amorim Bernstein, Santiago Lozano-Calderon, Edwin Choy, Francis J Hornicek, Zhenfeng Duan
BACKGROUND: Multi-drug resistance (MDR) remains a significant obstacle to successful chemotherapy treatment for osteosarcoma patients. One of the central causes of MDR is the overexpression of the membrane bound drug transporter protein P-glycoprotein (P-gp), which is the protein product of the MDR gene ABCB1. Though several methods have been reported to reverse MDR in vitro and in vivo when combined with anticancer drugs, they have yet to be proven useful in the clinical setting. RESULTS: The meta-analysis demonstrated that a high level of P-gp may predict poor survival in patients with osteosarcoma...
November 7, 2016: Oncotarget
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