0000000000293711

AUTHOR

Andrew C.g. Porter

showing 2 related works from this author

Functional characterization of protein variants of the human multidrug transporter ABCC2 by a novel targeted expression system in fibrosarcoma cells

2012

The multidrug resistance-associated protein 2 (MRP2/ABCC2) is involved in the efflux of endogenous and xenobiotic substrates, including several anticancer and antiviral drugs. The functional consequences of ABCC2 protein variants remain inconsistent, which may be due to shortcomings of the in vitro assays used. To study systematically the functional consequences of nonsynonymous ABCC2 variants, we used a novel “Screen and Insert” (ScIn) technology to achieve stable and highly reproducible expression of 13 ABCC2 variants in HT1080 cells. Western blotting revealed lower (30–65%) ABCC2 expression for D333G, R1174H, and R1181L as compared with wild type (WT; 100%), whereas the linked variant V1…

Nonsynonymous substitutionFibrosarcomaMutation MissenseATP-binding cassette transporterBiologyCell Line TumorGeneticsHumansGenetics (clinical)GeneticsAsianMultidrug resistance-associated protein 2Endoplasmic reticulumChloraminesWild typeGenetic VariationTetracyclineMolecular biologyMultidrug Resistance-Associated Protein 2Recombinant ProteinsBlack or African AmericanBlotHEK293 CellsGene Expression RegulationHaplotypesHT1080EffluxMultidrug Resistance-Associated ProteinsHuman Mutation
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Topoisomerase II{alpha}-dependent and -independent apoptotic effects of dexrazoxane and doxorubicin.

2009

Abstract Coadministration of the iron chelator dexrazoxane reduces by 80% the incidence of heart failure in cancer patients treated with anthracyclines. The clinical application of dexrazoxane is limited, however, because its ability to inhibit topoisomerase IIα (TOP2A) is feared to adversely affect anthracycline chemotherapy, which involves TOP2A-mediated generation of DNA double-strand breaks (DSB). Here, we investigated the apoptotic effects of dexrazoxane and the anthracycline doxorubicin, alone and in combination, in a tumor cell line with conditionally regulated expression of TOP2A. Each drug caused apoptosis that was only partly dependent on TOP2A. Unexpectedly, dexrazoxane was found…

DrugCancer ResearchAnthracyclinemedicine.medical_treatmentmedia_common.quotation_subjectAntineoplastic AgentsApoptosisPharmacologyHistonesAntigens NeoplasmCell Line TumormedicineHumansDoxorubicinAdverse effectPoly-ADP-Ribose Binding Proteinsmedia_commonCaspase 7ChemotherapyChemistryCaspase 3Gene Expression ProfilingCancermedicine.diseaseGlutathioneDNA-Binding ProteinsGene Expression Regulation NeoplasticDNA Topoisomerases Type IIOncologyApoptosisDoxorubicinCancer researchDexrazoxaneTumor Suppressor Protein p53Razoxanemedicine.drugMolecular cancer therapeutics
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