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https://www.readbyqxmd.com/read/28803989/mdr65-decreases-toxicity-of-multiple-insecticides-in-drosophila-melanogaster
#1
Haina Sun, Nicolas Buchon, Jeffrey G Scott
ABC transporters are ubiquitous membrane-bound proteins, present in both prokaryotes and eukaryotes. The major function of eukaryotic ABC transporters is to mediate the efflux of a variety of substrates (including xenobiotics) out of cells. ABC transporters have been widely investigated in humans, particularly for their involvement in multidrug resistance (MDR). Considerably less is known about their roles in transport and/or excretion in insects. ABC transporters are only known to function as exporters in insects...
August 10, 2017: Insect Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28796259/muc1-induces-acquired-chemoresistance-by-upregulating-abcb1-in-egfr-dependent-manner
#2
Wei Jin, Xiaodong Liao, Yaping Lv, Zhi Pang, Yuming Wang, Quanfu Li, Yahui Liao, Qing Ye, Guoqiang Chen, Kewen Zhao, Lei Huang
Chemoresistance contributes to cancer relapse and increased mortality in a variety of cancer types, raising a pressing need to better understand the underlying mechanism. MUC1 is abnormally overexpressed in numerous carcinomas and associated with poor prognosis. However, the functional significance of MUC1 in chemoresistance has not been fully elucidated. Here, we showed that MUC1 expression was considerably induced in cells that had acquired chemoresistance at both transcriptional and post-translational levels...
August 10, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28792917/association-between-abcb1-gene-polymorphism-and-renal-function-in-patients-with-hypertension-a-case-control-study
#3
Xiaofang Chen, Tao Zhou, Deguang Yang, Jinyang Lu
BACKGROUND A previous study found that target organ damage in patients with hypertension was related to genetic factors. The aim of our study aim was to explore the association between the ABCB1 gene and renal function injury induced by hypertension. MATERIAL AND METHODS We used a case-control study design. Patients with hypertension were enrolled from our hospital between July 2015 and December 2015. Questionnaire data included personal information, life habits and behavior. Clinical data included blood routine examination and liver and renal function...
August 9, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28792790/recent-developments-and-future-directions-for-the-use-of-pharmacogenomics-in-cardiovascular-disease-treatments
#4
Andrew Levy, Elliot Berinstein
Cardiovascular disease is still the leading cause of death worldwide. There are many environmental and genetic factors that play a role in the development of cardiovascular disease. The treatment of cardiovascular disease is beginning to move in the direction of personalized medicine by using biomarkers from patient's genome to design more effective treatment plans. Pharmacogenomics have already uncovered many links between genetic variation and response of many different drugs. Areas covered: This article will focus on the main polymorphisms that impact the risk of adverse effects and response efficacy of statins, clopidogrel, aspirin, β-blockers, warfarin dalcetrapib and vitamin E...
August 9, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28782465/pyramidatine-z88-sensitizes-vincristine-resistant-human-oral-cancer-kb-vcr-cells-to-chemotherapeutic-agents-by-inhibition-of-p-glycoprotein
#5
Zulong Liu, Hengrui Zhu, Shijin Qu, Lisha Tang, Lihuan Cao, Wenbo Yu, Xianmei Yang, Songmin Jiang, Dayuan Zhu, Changheng Tan, Long Yu
Multi-drug resistance (MDR) to anticancer drugs remains a major impediment in cancer therapy. A major goal for scientists is to identify more effective compounds that are able to circumvent MDR and simultaneously have minimal adverse side effects. Here, we reported that Pyramidatine (Z88), a cinnamic acid-derived bisamide compound isolated from the leaves of Aglaia perviridis, had potent anti-MDR activity. The average resistant fold (RF) of Z88 is 0.09 and 0.51 in KB/VCR (vincristine-resistant human oral cancer cells) and MCF-7/ADR (adriamycin-resistant human breast adenocarcinoma) cells...
August 3, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28776352/role-of-the-abcb1-drug-transporter-polymorphisms-in-the-pharmacokinetics-of-oseltamivir-in-humans-a-preliminary-report
#6
Yu Jung Cha, Jong Lyul Ghim
Oseltamivir is a substrate of P-glycoprotein, an efflux drug transporter encoded by ABCB1. The objective of this study was to assess the role of ABCB1 (c.1236C>T, c.2677G>T/A, and c.3435C>T) polymorphisms in the pharmacokinetics of oseltamivir and its active metabolite, oseltamivir carboxylate in humans. Nineteen healthy male subjects were enrolled, and their ABCB1 polymorphisms were evaluated. After the oral administration of 75 mg oseltamivir, the plasma concentrations of oseltamivir and oseltamivir carboxylate were measured...
September 2017: Journal of Korean Medical Science
https://www.readbyqxmd.com/read/28771725/tlr4-and-nf%C3%AE%C2%BAb-signaling-is-critical-for-taxol-resistance-in-ovarian-carcinoma-cells
#7
Nian-Kang Sun, Shang-Lang Huang, Ting-Chang Chang, Chuck C-K Chao
We report here that toll-like receptor 4 (TLR4) and ABCB1 are upregulated in SKOV3 ovarian carcinoma cells that acquired resistance to the anticancer drug taxol. Silencing of TLR4 using short-hairpin RNA sensitized taxol-resistant SKOV3 cells to taxol (4.6 fold), whereas ectopic expression of TLR4 in parental, taxol-sensitive SKOV3 cells or TLR4-null HEK293 cells induced taxol resistance (∼2 fold). A sub-lethal dose of taxol induced ABCB1 protein expression in taxol-resistant SKOV3 cells. Inactivation of TLR4 using chemical inhibitors (CLI-095 and AO-I) downregulated ABCB1 protein expression and enhanced the cytotoxic activity of taxol in taxol-resistant SKOV3 cells...
August 3, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28763429/genome-wide-association-study-of-cardiotoxicity-in-the-ncctg-n9831-alliance-adjuvant-trastuzumab-trial
#8
Daniel J Serie, Julia E Crook, Brian M Necela, Travis J Dockter, Xue Wang, Yan W Asmann, DeLisa Fairweather, Katelyn A Bruno, Gerardo Colon-Otero, Edith A Perez, E Aubrey Thompson, Nadine Norton
OBJECTIVES: The major clinical side effect of the ERBB2-targeted breast cancer therapy, trastuzumab, is a decline in the left ventricular ejection fraction (LVEF). Improved markers are needed to better identify patients susceptible to cardiotoxicity. METHODS: The NCCTG N9831 trial compared adjuvant doxorubicin and cyclophosphamide followed by either weekly paclitaxel (arm A); paclitaxel then trastuzumab (arm B); or concurrent paclitaxel and trastuzumab (arm C) in patients with HER2-positive breast cancer...
July 31, 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/28762597/visfatin-mediates-doxorubicin-resistance-in-human-non-small-cell-lung-cancer-via-akt-mediated-up-regulation-of-abcc1
#9
Zhili Cao, Naixin Liang, Huaxia Yang, Shanqing Li
OBJECTIVES: Non-small-cell lung cancer (NSCLC) is one of the leading causes of cancer deaths worldwide. Increasing levels of visfatin are correlated with worse clinical prognosis of NSCLC. However, the effects of visfatin on drug resistant are still not well illustrated. MATERIALS AND METHODS: Effects of visfatin on drug resistant cells were checked by CCK-8 kit. Gene and protein variations were measured by real-time PCR and western blot analysis, respectively. RESULTS: Our present data confirmed that expression of visfatin was significantly increased in NSCLC cells and tissues...
August 1, 2017: Cell Proliferation
https://www.readbyqxmd.com/read/28762371/imatinib-induced-ophthalmological-side-effects-in-gist-patients-are-associated-with-the-variations-of-egfr-slc22a1-slc22a5-and-abcb1
#10
H-B Qiu, W Zhuang, T Wu, S Xin, C-Z Lin, H-L Ruan, X Zhu, M Huang, J-L Li, X-Y Hou, Z-W Zhou, X-D Wang
Imatinib-induced ophthalmological side-effects, including conjunctiva hemorrhage and periorbital oedema, although very common and still remain relatively little understood. The present study investigated the effects of genetic polymorphisms of drug targets and membrane transporters on these side effects. We found that the minor allele of EGFR rs10258429 and SLC22A1 rs683369 were significant risk determinants of conjunctival hemorrhage with OR of 7.061 (95%CI=1.791-27.837, P=0.005 for EGFR rs10258429 CT+TT vs CC), and 4...
August 1, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28759738/abcb1-3435c-t-and-2677g-t-a-polymorphisms-in-polish-and-bosnian-crohn-s-disease-patients-a-preliminary-report
#11
Krzysztof Borecki, Iwona Zawada, Anna Pawinska-Matecka, Nermin Nusret Salkic, Beata Karakiewicz, Grażyna Adler
The role of ABCB1 single nucleotide polymorphisms (SNPs) in the development of Crohn's disease (CD) remains unclear. Due to inconsistent results of several European population-based studies and limited information on populations from Poland and Bosnia and Herzegovina (B&H), we conducted a preliminary association study of two main ABCB1 SNPs and CD. ABCB1 3435C>T and 2677G>T/A SNPs were analyzed in Polish and Bosnian CD patients (n = 85 and n = 30, respectively) and controls (n = 82 and n = 30, respectively) using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for 3435C>T and allele-specific PCR for 2677G>A/T SNP...
July 26, 2017: Bosnian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28753233/knockout-of-a-p-glycoprotein-gene-increases-susceptibility-to-abamectin-and-emamectin-benzoate-in-spodoptera-exigua
#12
Y-Y Zuo, J-L Huang, J Wang, Y Feng, T-T Han, Y-D Wu, Y-H Yang
P-glycoprotein [P-gp or the ATP-binding cassette transporter B1 (ABCB1)] is an important participant in multidrug resistance of cancer cells, yet the precise function of this arthropod transporter is unknown. The aim of this study was to determine the importance of P-gp for susceptibility to insecticides in the beet armyworm (Spodoptera exigua) using clustered regularly interspaced short palindromic repeats/CRISPR-associated 9 (CRISPR/Cas9) gene-editing technology. We cloned an open reading frame (ORF) encoding the S...
July 28, 2017: Insect Molecular Biology
https://www.readbyqxmd.com/read/28749817/prednisolone-and-prednisone-pharmacokinetics-in-pediatric-renal-transplant-recipients-a-prospective-study
#13
Ragnhild Heier Skauby, Anna Bjerre, Ingjerd Sæves, Nils Tore Vethe, Sara Bremer, Anja Svarstad, Stein Bergan
BACKGROUND: Prednisolone is a standard component of immunosuppressive protocols in renal transplantation (Tx) and despite standardized treatment regimens, adverse side effects are still frequent. The aim of this study was to characterize the pharmacokinetics of prednisolone and prednisone in pediatric renal transplant recipients in the first 52 weeks post Tx, to describe the relationship between prednisolone and prednisone, and to investigate a possible relationship between the development of new onset diabetes after Tx (NODAT) and glucocorticoid exposure...
July 26, 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28745577/advanced-cancer-pain-the-search-for-genetic-factors-correlated-with-interindividual-variability-in-opioid-requirement
#14
Maja Matic, Joost Lm Jongen, Laure Elens, Saskia N de Wildt, Dick Tibboel, Peter Ae Sillevis Smitt, Ron Hn van Schaik
AIM: To assess association between genetic variants and opioid requirement in cancer patients. MATERIALS & METHODS: A prospective observational trial of 243 advanced cancer patients with inadequate analgesia treated by the palliative care team was analyzed for ABCB1, ARRB2, COMT, GCH1, IL1RN, KCNJ6, OPRM1, RHBDF2, SCN9A and Stat6 polymorphisms. RESULTS: For patients carrying OPRM1 118AG/GG and COMT 472GG (Val158Val) or these genotypes alone, a significant higher median percentage dose increase was observed (95...
August 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28728917/global-alteration-of-the-drug-binding-pocket-of-human-p-glycoprotein-abcb1-by-substitution-of-fifteen-conserved-residues-reveals-a-negative-correlation-between-substrate-size-and-transport-efficiency
#15
Shahrooz Vahedi, Eduardo E Chufan, Suresh V Ambudkar
P-glycoprotein (P-gp), an ATP-dependent efflux pump, is linked to the development of multidrug resistance in cancer cells. However, the drug-binding sites and translocation pathways of this transporter are not yet well-characterized. We recently demonstrated the important role of tyrosine residues in regulating P-gp ATP hydrolysis via hydrogen bond formations with high affinity modulators. Since tyrosine is both a hydrogen bond donor and acceptor, and non-covalent interactions are key in drug transport, in this study we investigated the global effect of enrichment of tyrosine residues in the drug-binding pocket on the drug binding and transport of P-gp...
July 17, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28727815/polymorphisms-associated-with-everolimus-pharmacokinetics-toxicity-and-survival-in-metastatic-breast-cancer
#16
Tomas Pascual, María Apellániz-Ruiz, Cristina Pernaut, Cecilia Cueto-Felgueroso, Pablo Villalba, Carlos Álvarez, Luis Manso, Lucia Inglada-Pérez, Mercedes Robledo, Cristina Rodríguez-Antona, Eva Ciruelos
PURPOSE: Metastatic breast cancer (MBC) progressing after endocrine therapy frequently activates PI3K/AKT/mTOR pathway. The BOLERO-2 trial showed that everolimus-exemestane achieves increased progression free survival (PFS) compared with exemestane. However, there is great inter-patient variability in toxicity and response to exemestane-everolimus treatment. The objective of this study was to perform an exploratory study analyzing the implication of single nucleotide polymorphisms (SNPs) on outcomes from this treatment through a pharmacogenetic analysis...
2017: PloS One
https://www.readbyqxmd.com/read/28723497/pharmacogenomic-markers-of-targeted-therapy-toxicity-in-patients-with-metastatic-renal-cell-carcinoma
#17
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
#18
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
#19
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
#20
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
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