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Flavia da Cunha Vasconcelos, Marcos Antonio Mauricio Scheiner, Arthur Moellman-Coelho, André Luiz Mencalha, Ilana Zalcberg Renault, Vivian Mary Rumjanek, Raquel Ciuvalschi Maia
Despite the favorable clinical evolution of patients with chronic myeloid leukemia (CML), resistance or intolerance to imatinib is present in approximately 35% of patients. Sokal score is a widely used risk factor, however efflux and influx transporters are provisional risk factors implicated in imatinib resistance. This study analyzed Sokal score, ABCB1, ABCG2 and OCT1 mRNA transporter expression levels as well as P-glycoprotein expression and efflux transporters activity to seek a possible correlation between these factors and the molecular response at 12 months from imatinib start as well as 8-year overall survival (OS)...
October 12, 2016: Leukemia Research
Andrew Kl Goey, Tristan M Sissung, Cody J Peer, William D Figg
The histone deacetylase inhibitor valproic acid (VPA) has been used for many decades in neurology and psychiatry. The more recent introduction of the histone deacetylase inhibitors (HDIs) belinostat, romidepsin and vorinostat for treatment of hematological malignancies indicates the increasing popularity of these agents. Belinostat, romidepsin and vorinostat are metabolized or transported by polymorphic enzymes or drug transporters. Thus, genotype-directed dosing could improve pharmacotherapy by reducing the risk of toxicities or preventing suboptimal treatment...
October 21, 2016: Pharmacogenomics
V Némethová, F Rázga
No abstract text is available yet for this article.
October 21, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Xin-Yu Zhao, Lei Li, Xiao-Bo Wang, Rong-Jie Fu, Ya-Ping Lv, Wei Jin, Chao Meng, Guo-Qiang Chen, Lei Huang, Ke-Wen Zhao
China accounts for almost half of the total number of liver cancer cases and deaths worldwide, and hepatocellular carcinoma (HCC) is the most primary liver cancer. Snail family transcriptional repressor 2 (SNAI2) is known as an epithelial to mesenchymal transition-inducing transcription factor that drives neoplastic epithelial cells into mesenchymal phenotype. However, the roles of endogenous SNAI2 remain controversial in different types of malignant tumors. Herein, we surprisingly identify that anchorage-independent growth, including the formation of tumor sphere and soft agar colony, is significantly increased when SNAI2 expression is inhibited by shRNAs in HCC cells...
2016: PloS One
Kannan Sridharan, Rachna Kataria, Drishti Tolani, Shital Bendkhale, Nithya J Gogtay, Urmila M Thatte
INTRODUCTION: CYP2C19 and P2Y12 polymorphisms have been claimed to alter the pharmacodynamic response to clopidogrel. ABCB1 polymorphism has been associated with the efflux of clopidogrel resulting in decreased bioavailability. Due to paucity of data from Indian population, the present study was undertaken to evaluate the association of genetic polymorphisms of CYP2C19, P2Y12, and ABCB1 with inhibition of platelet aggregation (IPA) by clopidogrel. METHODS: Healthy adults (n = 90) of either gender were administered single dose of 300 mg clopidogrel...
July 2016: Indian Journal of Pharmacology
Vera Erdman, Ilsia Tuktarova, Timur Nasibullin, Ianina Timasheva, Olga Mustafina
OBJECTIVE: Physiological and biochemical changes during aging alter drug metabolism. Drug intake is increased with age because of cumulative morbidity, in particular, high prevalence of cardiovascular diseases. Antihypertensive medications are the most commonly used drugs. Individual drug sensitivity or resistance may be influenced by the variance of the "pharmacological response" genes.Our purpose was to search for the polymorphic variants of "pharmacological response" genes associated with survival in different age periods...
September 2016: Journal of Hypertension
Tristram A Lett, Henrik Walter, Eva J Brandl
Genetic variation underlies both the response to antidepressant treatment and the occurrence of side effects. Over the past two decades, a number of pharmacogenetic variants, among these the SCL6A4, BDNF, FKBP5, GNB3, GRIK4, and ABCB1 genes, have come to the forefront in this regard. However, small effects sizes, mixed results in independent samples, and conflicting meta-analyses results led to inherent difficulties in the field of pharmacogenetics translating these findings into clinical practice. Nearly all antidepressant pharmacogenetic variants have potentially pleiotropic effects in which they are associated with major depressive disorder, intermediate phenotypes involved in emotional processes, and brain areas affected by antidepressant treatment...
October 17, 2016: CNS Drugs
Luis Sala-Icardo, Amalia Lamana, Ana María Ortiz, Elena García Lorenzo, Pablo Moreno Fresneda, Rosario García-Vicuña, Isidoro González-Álvaro
OBJECTIVE: To analyze the effect of single nucleotide polymorphisms (SNPs) with well-known functional impact of methylenetetrahydrofolatereductase (MTHFR; rs1801131 and rs1801133), the membrane transporter ABCB1 (rs1045642), the AICAR transformylase/IMP cyclohydrolase (ATIC; rs2372536) and folyl-polyglutamatesynthetase (FPGS; rs1544105), on liver and bone marrow toxicity of methotrexate (MTX). PATIENTS AND METHODS: We analyzed 1415 visits from 350 patients of the PEARL (Princesa Early Arthritis Register Longitudinal) study: (732 with MTX, 683 without MTX)...
October 14, 2016: Reumatología Clinica
Hongbin Huang, Cong Peng, Yong Liu, Xu Liu, Qicong Chen, Zunnan Huang
BACKGROUND: Parkinson's disease (PD) is the second most frequent neurodegenerative disorder. Previous publications have investigated the association of NOS1 and ABCB1 polymorphisms with PD risk. However, those studies have provided some contradictory results. METHODS: Literature searches were performed using PubMed, Embase, PDgene, China National Knowledge Infrastructure database, and Google Scholar. Odds ratios (ORs) with 95% confidence intervals (CIs) were applied to evaluate the strength of association...
October 2016: Medicine (Baltimore)
Guillermo Gervasini, Carlos Jara, Clara Olier, Nuria Romero, Ruth Martínez, Juan Antonio Carrillo
AIMS: Anastrozole, an aromatase inhibitor widely used in breast cancer, has recently been pointed out as a P-glycoprotein (ABCB1) substrate. We have aimed to determine whether ABCB1 single-nucleotide polymorphisms (SNPs) can affect anastrozole plasma concentrations in these patients. In addition, we assessed the impact of SNPs in CYP19A1 and TCL1A on the development of arthralgia and cancer recurrence in our series. METHODS: One-hundred-and-ten postmenopausal women with hormone receptor-positive breast cancer were included...
October 17, 2016: British Journal of Clinical Pharmacology
Jesús Sánchez-Ramos, Cristina Lucía Dávila-Fajardo, Pablo Toledo Frías, Xando Díaz Villamarín, Luis Javier Martínez-González, Susana Martínez Huertas, Francisco Burillo Gómez, Juan Caballero Borrego, Alicia Bautista Pavés, Mª Carmen Marín Guzmán, José Antonio Ramirez Hernández, Concepción Correa Vilches, Jose Cabeza Barrera
BACKGROUND: Clopidogrel has provided beneficial effects in acute coronary syndrome and percutaneous coronary intervention. Different polymorphisms have been associated with differences in clopidogrel response. The aim of this study was to check if CYP2C19/ABCB1-genotype-guided strategy reduces the rates of cardiovascular events and bleeding. METHODS: This experimental study included patients undergoing percutaneous coronary intervention with stent. The prospective genotype-guided strategy (intervention group) was compared against a retrospective non-tailored strategy (control group)...
September 26, 2016: International Journal of Cardiology
Savitha Varatharajan, John C Panetta, Ajay Abraham, Sreeja Karathedath, Ezhilpavai Mohanan, Kavitha M Lakshmi, Nancy Arthur, Vivi M Srivastava, Sandeep Nemani, Biju George, Alok Srivastava, Vikram Mathews, Poonkuzhali Balasubramanian
PURPOSE: Chemotherapy drug resistance and relapse of the disease have been the major factors limiting the success of acute myeloid leukemia (AML) therapy. Several factors, including the pharmacokinetics (PK) of Cytarabine (Ara-C) and Daunorubicin (Dnr), could contribute to difference in treatment outcome in AML. METHODS: In the present study, we evaluated the plasma PK of Dnr, the influence of genetic polymorphisms of genes involved in transport and metabolism of Dnr on the PK, and also the influence of these factors on clinical outcome...
October 13, 2016: Cancer Chemotherapy and Pharmacology
Martin Bauer, Rudolf Karch, Nicolas Tournier, Salvatore Cisternino, Wolfgang Wadsak, Marcus Hacker, Peter Marhofer, Markus Zeitlinger, Oliver Langer
: P-glycoprotein (ABCB1) is expressed at the blood-retinal barrier (BRB) where it may control distribution of drugs from blood to the retina and thereby influence drug efficacy and toxicity. METHODS: We performed PET scans with the ABCB1 substrate (R)-(11)C-verapamil in 5 healthy male volunteers without and with concurrent infusion of the ABCB1 inhibitor tariquidar. We estimated the rate constants for radiotracer transfer across the BRB (K1, k2) and total retinal distribution volume VT...
October 13, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Yvonne Voges, Martin Michaelis, Florian Rothweiler, Torsten Schaller, Constanze Schneider, Katharina Politt, Marco Mernberger, Andrea Nist, Thorsten Stiewe, Mark N Wass, Franz Rödel, Jindrich Cinatl
Resistance formation after initial therapy response (acquired resistance) is common in high-risk neuroblastoma patients. YM155 is a drug candidate that was introduced as a survivin suppressant. This mechanism was later challenged, and DNA damage induction and Mcl-1 depletion were suggested instead. Here we investigated the efficacy and mechanism of action of YM155 in neuroblastoma cells with acquired drug resistance. The efficacy of YM155 was determined in neuroblastoma cell lines and their sublines with acquired resistance to clinically relevant drugs...
October 13, 2016: Cell Death & Disease
Stefanie Kraege, Sebastian C Köhler, Michael Wiese
Chalcones are easily synthesized natural precursors of secondary plant metabolites, and their derivatives show various biological activities including inhibition of ABC transporters. Especially, their role as inhibitors of ABCG2, the most recently discovered ABC transporter involved in multidrug resistance, inspired the synthesis of new structurally diverse derivatives. Therefore, we combined the typical chalcone moiety with several acid chlorides by using an amide linker at position 2', 3', or 4' on ring A of the chalcone...
October 13, 2016: ChemMedChem
Yang Yang, Jian-Ge Qiu, Yong Li, Jin-Ming Di, Wen-Ji Zhang, Qi-Wei Jiang, Di-Wei Zheng, Yao Chen, Meng-Ning Wei, Jia-Rong Huang, Kun Wang, Zhi Shi
The RNA-guided clustered regularly interspaced short palindromic (CRISPR) in combination with a CRISPR-associated nuclease 9 (Cas9) nuclease system is a new rapid and precise technology for genome editing. In the present study, we applied the CRISPR/Cas9 system to target ABCB1 (also named MDR1) gene which encodes a 170 kDa transmembrane glycoprotein (P-glycoprotein/P-gp) transporting multiple types of chemotherapeutic drugs including taxanes, epipodophyllotoxins, vinca alkaloids and anthracyclines out of cells to contribute multidrug resistance (MDR) in cancer cells...
2016: American Journal of Translational Research
Manal A Safan, Nesreen G Elhelbawy, Dina A Midan, Heba F Khader
BACKGROUND: The most common cause of nephrotic syndrome (NS) is idiopathic nephrotic syndrome (INS), also called nephrosis. Although most patients respond to steroid therapy, there is unequal response to treatment suggesting the involvement of genetic factors. The current study was conducted to evaluate the influence of two single nucleotide polymorphisms (SNPs) in ABCB1 (C3435T and C1236T) on the steroid treatment response in INS children. MATERIALS AND METHODS: Genotyping of ABCB1 C3435T and C1236T polymorphisms by real time PCR were conducted on 120 INS children, 80 steroid sensitive (SS) and 40 steroid resistant (SR)...
October 8, 2016: British Journal of Biomedical Science
Minoru Kobayashi, Ryo Funayama, Shinobu Ohnuma, Michiaki Unno, Keiko Nakayama
We determined the gene expression profiles for 48 ATP binding cassette (ABC) transporters in matched colon cancer and normal colon tissues in order to provide insight into the mechanisms underlying expression of transporters related to colon carcinogenesis. The expression of ABCB1, ABCC1, ABCC2, ABCC3, and ABCG2 was altered in association with colon carcinogenesis. Among these transporters, the expression of ABCC3 was repressed by Wnt signaling pathway in colon cancer cell lines. Knockdown of the pathway components transcription factor 7-like 2 (TCF7L2) or β-catenin thus increased ABCC3 expression, whereas activation of Wnt signaling with inhibitors of glycogen synthase kinase-3β (GSK-3β) reduced it...
October 6, 2016: Cancer Science
R Feng, H X Zhang, H G Zhang, C F Zhang
We carried out a case-control study to examine the relationship between the ATP-binding cassette subfamily B member 1 (ABCB1) gene polymorphisms C1236T, G2677T, and C3435T and risk of acute leukemia in a Chinese population. Between May 2013 and April 2015, we recruited 164 acute leukemia patients and 285 healthy controls, and determined polymorphism genotypes by polymerase chain reaction-restriction fragment length polymorphism. Using unconditional logistic regression analysis, we observed that in comparison to the wild-type sequence, the TT genotype [odds ratio (OR) = 2...
September 2, 2016: Genetics and Molecular Research: GMR
Y Q Jiang, X P Xu, Q M Guo, X C Xu, Q Y Liu, S H An, J L Xu, F Su, J B Tai
Drug resistance in cells is a major impedance to successful treatment of lung cancer. Taxus chinensis var. inhibits the growth of tumor cells and promotes the synthesis of interleukins 1 and 2 and tumor necrosis factor, enhancing immune function. In this study, T. chinensis var.-induced cell death was analyzed in lung cancer cells (H460) enriched for stem cell growth in a defined serum-free medium. Taxus-treated stem cells were also analyzed for Rhodamine 123 (Rh-123) expression by flow cytometry, and used as a standard functional indicator of MDR...
September 2, 2016: Genetics and Molecular Research: GMR
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