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https://www.readbyqxmd.com/read/28723497/pharmacogenomic-markers-of-targeted-therapy-toxicity-in-patients-with-metastatic-renal-cell-carcinoma
#1
Guillermo de Velasco, Kathryn P Gray, Lana Hamieh, Yuksel Urun, Hallie A Carol, Andre P Fay, Sabina Signoretti, David J Kwiatkowski, David F McDermott, Matthew Freedman, Mark M Pomerantz, Toni K Choueiri
BACKGROUND: Targeted therapy (TT) in metastatic renal cell carcinoma (mRCC) may be associated with a high rate of toxicity that undermines treatment efficacy and patient quality of life. Polymorphisms in genes involved in the pharmacokinetic pathways of TTs may predict toxicity. OBJECTIVE: To investigate whether selected single-nucleotide polymorphisms (SNPs) in three core genes involved in the metabolism and transport of sunitinib and the mTOR inhibitors everolimus and temsirolimus are associated with adverse events (AEs)...
December 15, 2016: European Urology Focus
https://www.readbyqxmd.com/read/28719598/the-predictive-value-of-abcb1-abcg2-cyp3a4-5-and-cyp2d6-polymorphisms-for-risperidone-and-aripiprazole-plasma-concentrations-and-the-occurrence-of-adverse-drug-reactions
#2
C Rafaniello, M Sessa, F F Bernardi, M Pozzi, S Cheli, D Cattaneo, S Baldelli, M Molteni, R Bernardini, F Rossi, E Clementi, C Bravaccio, S Radice, A Capuano
We investigated in ninety Caucasian pediatric patients the impact of the main polymorphisms occurring in CYP3A, CYP2D6, ABCB1 and ABCG2 genes on second-generation antipsychotics plasma concentrations, and their association with the occurrence of adverse drug reactions. Patients with the CA/AA ABCG2 genotype had a statistically significant lower risperidone plasma concentration/dose ratio (Ct/ds) (P-value: 0.007) and an higher estimated marginal probability of developing metabolism and nutrition disorders as compared to the ABCG2 c...
July 18, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28718515/impact-of-single-nucleotide-polymorphisms-on-plasma-concentrations-of-efavirenz-and-lopinavir-ritonavir-in-chinese-children-infected-with-the-human-immunodeficiency-virus
#3
Xia Liu, Qing Ma, Yan Zhao, Weiwei Mu, Xin Sun, Yuewu Cheng, Huiping Zhang, Ye Ma, Fujie Zhang
Single-nucleotide polymorphisms (SNPs) in the genes that encode the cytochrome P450 (CYP) drug metabolizing enzymes and drug transporters have been reported to influence antiretroviral drug pharmacokinetics. While primarily metabolized by CYP2B6 and -3A, efavirenz (EFV) and lopinavir/ritonavir (LPV/r) are substrates of P-glycoprotein and solute carrier organic (SLCO) anion transporter, respectively OBJECTIVE: To investigate the association between SNPs and efavirenz (EFV) or lopinavir/ritonavir (LPV/r) concentrations in Chinese children infected with the human immunodeficiency virus (HIV) METHODS: Genotyping was performed on CYP2B6 516G→T, -1459C→T, and -983T→C, ABCB1 3435C→T, and SLCO1B1 521T→C in 229 HIV-infected Chinese pediatric patients with an age range from 4...
July 17, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28714181/involvement-of-adenosine-triphosphate-binding-cassette-subfamily-b-member-1-in-the-augmentation-of-triacylglycerol-excretion-by-propionibacterium-acnes-in-differentiated-hamster-sebocytes
#4
Koji Mizuno, Noriko Akimoto, Mina Kawamura, Keisuke Nakase, Norihisa Noguchi, Takashi Sato
An onset of acne, a common inflammatory skin disease, is associated with excess sebum production and secretion in sebaceous glands. Because Propionibacterium acnes has been reported to augment intracellular sebum accumulation in sebaceous glands in hamsters, it remains unclear whether P. acnes influences sebum secretion from differentiated sebocytes. Both P. acnes culture media (Acnes73-CM) and formalin-killed P. acnes (F-Acnes73) dose-dependently increased the extracellular levels of triacylglycerol (TG), a major sebum component, and Rhodamine 123, a substrate of adenosine triphosphate-binding cassette (ABC) transporter, from differentiated hamster sebocytes (DHS)...
July 17, 2017: Journal of Dermatology
https://www.readbyqxmd.com/read/28710036/effect-of-polymorphisms-in-transporter-genes-on-dosing-efficacy-and-toxicity-of-maintenance-therapy-in-children-with-acute-lymphoblastic-leukemia
#5
Guillermo Gervasini, Silvia G de Murillo, Mercedes Jiménez, María D de la Maya, Jose M Vagace
The aim of the present work was to assess whether polymorphisms in genes coding for drug transport proteins may influence dosing, efficacy and toxicity of maintenance therapy with methotrexate (MTX) and 6-mercaptopurine (6MP) in childhood acute lymphoblastic leukemia (ALL). A total of 41 children with ALL were screened for 10 SNPs in the SLC19A1, ABCB1, ABCC2, ABCC4 and ABCG2 transporter genes by means of direct sequencing. Carriers of the ABCC4 934CC and ABCB1 1236TT genotypes received a lower percentage of the protocol-recommended starting dose of MTX (62...
July 11, 2017: Gene
https://www.readbyqxmd.com/read/28707077/association-of-abcb1-promoter-methylation-with-aspirin-exposure-platelet-function-and-clinical-outcomes-in-chinese-intracranial-artery-stenosis-patients
#6
Xingang Li, Kun Zhao, Ning Ma, Shusen Sun, Zhongrong Miao, Zhigang Zhao
PURPOSE: DNA methylation typically acts to repress gene transcription. ABCB1 is involved in the intestinal absorption of aspirin. We aimed to investigate the impact of methylation status of ABCB1 promoter on aspirin exposure, platelet function, and clinical outcomes in Chinese intracranial artery stenosis patients receiving antiplatelet treatment. METHODS: Symptomatic intracranial artery stenosis patients (without carrying CYP2C19 loss-of-function alleles) receiving antiplatelet therapy were enrolled in this study...
July 13, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28700899/pegylated-liposomal-formulation-of-doxorubicin-overcomes-drug-resistance-in-a-genetically-engineered-mouse-model-of-breast-cancer
#7
András Füredi, Kornélia Szebényi, Szilárd Tóth, Mihály Cserepes, Lilla Hámori, Veronika Nagy, Edina Karai, Péter Vajdovich, Tímea Imre, Pál Szabó, Dávid Szüts, József Tóvári, Gergely Szakács
Success of cancer treatment is often hampered by the emergence of multidrug resistance (MDR) mediated by P-glycoprotein (ABCB1/Pgp). Doxorubicin (DOX) is recognized by Pgp and therefore it can induce therapy resistance in breast cancer patients. In this study our aim was to evaluate the susceptibility of the pegylated liposomal formulation of doxorubicin (PLD/Doxil®/Caelyx®) to MDR. We show that cells selected to be resistant to DOX are cross-resistant to PLD and PLD is also ineffective in an allograft model of doxorubicin-resistant mouse B-cell leukemia...
July 9, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28698198/abcb1-mediates-cabazitaxel-docetaxel-cross-resistance-in-advanced-prostate-cancer
#8
Alan P Lombard, Chengfei Liu, Cameron M Armstrong, Vito Cucchiara, Xinwei Gu, Wei Lou, Christopher P Evans, Allen C Gao
in research have added several new therapies for castration-resistant prostate cancer (CRPC), greatly augmenting our ability to treat patients. However, CRPC remains an incurable disease due to the development of therapeutic resistance and the existence of cross-resistance between available therapies. Understanding the interplay between different treatments will lead to improved sequencing and the creation of combinations which overcome resistance and prolong survival. Whether there exists cross-resistance between docetaxel and the next-generation taxane cabazitaxel is poorly understood...
July 11, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28696411/combined-study-of-genetic-and-epigenetic-biomarker-risperidone-treatment-efficacy-in-chinese-han-schizophrenia-patients
#9
Y Shi, M Li, C Song, Q Xu, R Huo, L Shen, Q Xing, D Cui, W Li, J Zhao, L He, S Qin
Nowadays, risperidone is an atypical antipsychotic drug that has been increasingly used for treatment and maintenance therapy in schizophrenia. However, partially affected by genetic or environmental factors, there is significant difference in treatment outcomes among patients. In this study, we aimed to interpret the difference between good and poor responders treated with risperidone in both genetic and epigenetic levels in 288 mainland Chinese patients. We recruited a Henan cohort including 98 patients as initial discovery group and then confirmed our results in Shanghai cohort...
July 11, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28693170/prognostic-significance-of-abcb1-in-stage-i-lung-adenocarcinoma
#10
Fenfei Zou, Masahiro Seike, Rintaro Noro, Shinobu Kunugi, Kaoru Kubota, Akihiko Gemma
Cancer stem cell (CSC) properties have been recently proposed to explain tumor carcinogenesis and multidrug resistance in several human cancers, including non-small cell lung cancer (NSCLC). The present study examined the protein expression of three CSC-associated markers, namely ATP binding cassette subfamily B member 1 (ABCB1), aldehyde dehydrogenase 1 family member A1 (ALDH1A1) and cluster of differentiation (CD) 44, by immunohistochemistry in 194 NSCLC patients who underwent complete resection of NSCLC tumors...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28687752/heliosterpenoids-a-and-b-two-novel-jatrophane-derived-diterpenoids-with-a-5-6-4-6-ring-system-from-euphorbia-helioscopia
#11
Zhen-Peng Mai, Gang Ni, Yan-Fei Liu, Li Li, Guo-Ru Shi, Xin Wang, Jia-Yuan Li, De-Quan Yu
Heliosterpenoids A and B (1 and 2), two unprecedented jatrophane-derived diterpenoid esters with a novel 5/6/4/6-fused tetracyclic ring skeleton, were isolated from the whole plants of Euphorbia helioscopia. The structures of 1 and 2 were elucidated by extensive spectroscopic methods and electronic circular dichroism (ECD) analyses. The plausible biogenetic pathways of 1 and 2 were postulated. 1 and 2 were found to be potent inhibitors of P-glycoprotein (ABCB1) and 1 also exhibited cytotoxicity against MDA-MB-231 cell lines...
July 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28687494/sphingolipid-abnormalities-in-cancer-multidrug-resistance-chicken-or-egg
#12
REVIEW
Wing-Kee Lee, Richard N Kolesnick
The cancer multidrug resistance (MDR) phenotype encompasses a myriad of molecular, genetic and cellular alterations resulting from progressive oncogenic transformation and selection. Drug efflux transporters, in particular the MDR P-glycoprotein ABCB1, play an important role in MDR but cannot confer the complete phenotype alone indicating parallel alterations are prerequisite. Sphingolipids are essential constituents of lipid raft domains and directly participate in functionalization of transmembrane proteins, including providing an optimal lipid microenvironment for multidrug transporters, and are also perturbed in cancer...
July 4, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28686677/mdr1a-deficiency-restrains-tumor-growth-in-murine-colitis-associated-carcinogenesis
#13
Eva Maria Hennenberg, Annette Eyking, Henning Reis, Elke Cario
Patients with Ulcerative Colitis (UC) have an increased risk to develop colitis-associated colorectal cancer (CAC). Here, we found that protein expression of ABCB1 (ATP Binding Cassette Subfamily B Member 1) / MDR1 (multidrug resistance 1) was diminished in the intestinal mucosa of patients with active UC with or without CAC, but not in non-UC patients with sporadic colon cancer. We investigated the consequences of ABCB1/MDR1 loss-of-function in a common murine model for CAC (AOM/DSS). Mice deficient in MDR1A (MDR1A KO) showed enhanced intratumoral inflammation and cellular damage, which were associated with reduced colonic tumor size and decreased degree of dysplasia, when compared to wild-type (WT)...
2017: PloS One
https://www.readbyqxmd.com/read/28678049/impact-of-abcb1-abcg2-and-cyp3a5-polymorphisms-on-plasma-trough-concentrations-of-apixaban-in-japanese-patients-with-atrial-fibrillation
#14
Satoshi Ueshima, Daiki Hira, Ryo Fujii, Yuuma Kimura, Chiho Tomitsuka, Takuya Yamane, Yohei Tabuchi, Tomoya Ozawa, Hideki Itoh, Minoru Horie, Tomohiro Terada, Toshiya Katsura
OBJECTIVES: During anticoagulant therapy, major bleeding is one of the most severe adverse effects. This study aimed to evaluate the relationships between ABCB1, ABCG2, and CYP3A5 polymorphisms and plasma trough concentrations of apixaban, a direct inhibitor of coagulation factor X. PATIENTS AND METHODS: A total of 70 plasma concentrations of apixaban from 44 Japanese patients with atrial fibrillation were analyzed. In these analyses, the plasma trough concentration/dose (C/D) ratio of apixaban was used as a pharmacokinetic index and all data were stratified according to the presence of ABCB1 (ABCB1 1236C>T, 2677G>T/A, and 3435C>T), ABCG2 (ABCG2 421C>A), and CYP3A5 (CYP3A5*3) polymorphisms...
July 3, 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/28677036/%C3%AE-np73-regulates-the-expression-of-the-multidrug-resistance-genes-abcb1-and-abcb5-in-breast-cancer-and-melanoma-cells-a-short-report
#15
Habib A M Sakil, Marina Stantic, Johanna Wolfsberger, Suzanne Egyhazi Brage, Johan Hansson, Margareta T Wilhelm
PURPOSE: Multidrug resistance (MDR) is a major cause of treatment failure. In cancer cells, MDR is often caused by an increased efflux of therapeutic drugs mediated by an up-regulation of ATP binding cassette (ABC) transporters. It has previously been shown that oncogenic ΔNp73 plays an important role in chemo-resistance. Here we aimed at unraveling the role of ΔNp73 in regulating multidrug resistance in breast cancer and melanoma cells. METHODS: KEGG pathway analysis was used to identify pathways enriched in breast cancer samples with a high ΔNp73 expression...
July 4, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/28676933/association-of-nr1i2-cyp3a5-and-abcb1-genetic-polymorphisms-with-variability-of-temsirolimus-pharmacokinetics-and-toxicity-in-patients-with-metastatic-bladder-cancer
#16
Litaty C Mbatchi, Matthieu Gassiot, Philippe Pourquier, Alejando Goberna, Hakim Mahammedi, Loic Mourey, Florence Joly, Serge Lumbroso, Alexandre Evrard, Nadine Houede
PURPOSE: Temsirolimus is a mammalian target of rapamycin (mTOR) inhibitor that exhibits antitumor activity in renal cell carcinoma and mantle cell lymphoma. The metabolism of temsirolimus and its active metabolite sirolimus mainly depends on cytochrome P450 3A4/5 (CYP3A4/A5) and the ABCB1 transporter. Differently from sirolimus, no pharmacogenetic study on temsirolimus has been conducted. Therefore, the aim of this pilot study was to identify genetic determinants of the inter-individual variability in temsirolimus pharmacokinetics and toxicity...
July 4, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28676669/carfilzomib-resistance-due-to-abcb1-mdr1-overexpression-is-overcome-by-nelfinavir-and-lopinavir-in-multiple-myeloma
#17
A Besse, S C Stolze, L Rasche, N Weinhold, G J Morgan, M Kraus, J Bader, H S Overkleeft, L Besse, C Driessen
Proteasome inhibitor carfilzomib has activity superior to bortezomib and is increasingly incorporated in multiple myeloma (MM) frontline therapy and relapsed settings. Most MM patients ultimately experience proteasome inhibitor-refractory disease, an unmet medical need with poorly understood biology and dismal outcome. Pharmacologic targeting of ABCB1 improved patient outcomes, including MM, but suffered from adverse drug effects and insufficient plasma concentrations. Proteomics analysis identified ABCB1 overexpression as the most significant change in carfilzomib-resistant MM cells...
July 5, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28676627/sorghum-dw2-encodes-a-protein-kinase-regulator-of-stem-internode-length
#18
Josie L Hilley, Brock D Weers, Sandra K Truong, Ryan F McCormick, Ashley J Mattison, Brian A McKinley, Daryl T Morishige, John E Mullet
Sorghum is an important C4 grass crop grown for grain, forage, sugar, and bioenergy production. While tall, late flowering landraces are commonly grown in Africa, short early flowering varieties were selected in US grain sorghum breeding programs to reduce lodging and to facilitate machine harvesting. Four loci have been identified that affect stem length (Dw1-Dw4). Subsequent research showed that Dw3 encodes an ABCB1 auxin transporter and Dw1 encodes a highly conserved protein involved in the regulation of cell proliferation...
July 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28673292/effect-of-pharmacogenetics-on-plasma-lumefantrine-pharmacokinetics-and-malaria-treatment-outcome-in-pregnant-women
#19
Ritah F Mutagonda, Appolinary A R Kamuhabwa, Omary M S Minzi, Siriel N Massawe, Muhammad Asghar, Manijeh V Homann, Anna Färnert, Eleni Aklillu
BACKGROUND: Pregnancy has considerable effects on the pharmacokinetic properties of drugs used to treat uncomplicated Plasmodium falciparum malaria. The role of pharmacogenetic variation on anti-malarial drug disposition and efficacy during pregnancy is not well investigated. The study aimed to examine the effect of pharmacogenetics on lumefantrine (LF) pharmacokinetics and treatment outcome in pregnant women. METHODS: Pregnant women with uncomplicated falciparum malaria were enrolled and treated with artemether-lumefantrine (ALu) at Mkuranga and Kisarawe district hospitals in Coast Region of Tanzania...
July 3, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28671633/l1210-cells-overexpressing-abcb1-drug-transporters-are-resistant-to-inhibitors-of-the-n-and-o-glycosylation-of-proteins
#20
Lucia Pavlikova, Mario Seres, Milan Hano, Viera Bohacova, Ivana Sevcikova, Tomas Kyca, Albert Breier, Zdena Sulova
Overexpression of P-glycoprotein (P-gp, drug transporter) in neoplastic cells is the most frequently observed molecular cause of multidrug resistance. Here, we show that the overexpression of P-gp in L1210 cells leads to resistance to tunicamycin and benzyl 2-acetamido-2-deoxy-α-d-galactopyranoside (GalNAc-α-O-benzyl). Tunicamycin induces both glycosylation depression and ubiquitination improvement of P-gp. However, the latter is not associated with large increases in molecular mass as evidence for polyubiquitination...
July 3, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
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