@inbook{MTMT:2511378,
	title = {Human Stem-Cell-Derived Cardiomyocytes in Drug Discovery and Toxicity Testing},
	url = {https://m2.mtmt.hu/api/publication/2511378},
	author = {Szebényi, Kornélia and Péntek, Adrienn and Varga, Nóra and Erdei, Zsuzsa and Vőfély, Gergő and Orbán, Tamás I. and Sarkadi, Balázs and Apáti, Ágota},
	booktitle = {Handbook of Nanotoxicology, Nanomedicine and Stem Cell Use in Toxicology},
	doi = {10.1002/9781118856017.ch15},
	unique-id = {2511378},
	abstract = {In this chapter, we review the methods of cardiomyocyte generation from human pluripotent and somatic stem cells, as well as from adult tissues through transdifferentiation. We describe the methods for stable genetic modification of human pluripotent stem cells, which can be applied to generate appropriate cardiomyocytes (CM) for drug screening, and introduce current methodologies for the preparation of cardiac progenitors for large-scale production. An overview of the current technologies for examining cardiotoxicity and the related key screening systems for drug development is provided. We describe selective reporter systems, which can be introduced into differentiated human CM and the potential application of human CM for disease models and personalized drug development. Finally, the future perspectives of these special systems in drug discovery are discussed.},
	year = {2014},
	pages = {267-298},
	orcid-numbers = {Szebényi, Kornélia/0000-0003-1558-8372; Orbán, Tamás I./0000-0002-3424-3428; Sarkadi, Balázs/0000-0003-0592-4539}
}

@{MTMT:2507786,
	title = {Quantitative analysis of DNA transposon-mediated gene delivery: the Sleeping Beauty system as an example},
	url = {https://m2.mtmt.hu/api/publication/2507786},
	author = {Kolacsek, Orsolya and Izsvák, Zsuzsa and Ivics, Zoltán and Sarkadi, Balázs and Orbán, Tamás I.},
	booktitle = {Genomics III - Methods, Techniques and Applications},
	unique-id = {2507786},
	year = {2014},
	orcid-numbers = {Sarkadi, Balázs/0000-0003-0592-4539; Orbán, Tamás I./0000-0002-3424-3428}
}

@article{MTMT:2156158,
	title = {ABCMdb: a database for the comparative analysis of protein mutations in ABC transporters, and a potential framework for a general application.},
	url = {https://m2.mtmt.hu/api/publication/2156158},
	author = {Gyimesi, Gergely and Borsodi, D and Sarankó, Hajnalka and Tordai, Hedvig and Sarkadi, Balázs and Hegedűs, Tamás},
	doi = {10.1002/humu.22138},
	journal-iso = {HUM MUTAT},
	journal = {HUMAN MUTATION},
	volume = {33},
	unique-id = {2156158},
	issn = {1059-7794},
	abstract = {To overcome the pathological phenomena caused by altered function of ABC (ATP Binding Cassette) proteins, their mechanisms of action are extensively investigated, often involving the design of mutant constructs for experiments. Designing mutagenetic constructs, interpreting the result of mutagenetic experiments, and finding individual genetic variants require an extensive knowledge of previously published mutations. To aid the recapitulation of mutations described in the literature, we set up a database of ABC protein mutations (ABCMdb) extracted from full-text papers using an automatic mining approach. We have also developed a Web application interface to compare mutations in different ABC proteins using sequence alignments and to interactively map the mutations to 3D structural models. Currently our database contains protein mutations published for ABCB1, ABCB11, ABCC1, ABCC6, ABCC7, and the proteins of the ABCG subfamily. The database will be extended to include other members and subfamilies, and to provide information on whether or not a mutation is disease causing, represents a high-incidence polymorphism, or was generated only in vitro. The ABCMdb database should already help to compare the effects of mutations at homologous positions in different ABC proteins, and its interactive tools aim to advance the design of experiments for a wider range of proteins.},
	year = {2012},
	eissn = {1098-1004},
	pages = {1547-1556},
	orcid-numbers = {Tordai, Hedvig/0000-0002-0875-5569; Sarkadi, Balázs/0000-0003-0592-4539; Hegedűs, Tamás/0000-0002-0331-9629}
}

@article{MTMT:1760809,
	title = {Calcium signaling in pluripotent stem cells.},
	url = {https://m2.mtmt.hu/api/publication/1760809},
	author = {Apáti, Ágota and Pászty, Katalin and Erdei, Zsuzsa and Szebényi, Kornélia and Homolya, László and Sarkadi, Balázs},
	doi = {10.1016/j.mce.2011.08.038},
	journal-iso = {MOL CELL ENDOCRINOL},
	journal = {MOLECULAR AND CELLULAR ENDOCRINOLOGY},
	volume = {353},
	unique-id = {1760809},
	issn = {0303-7207},
	abstract = {Pluripotent stem cells represent a new source of biological material allowing the exploration of signaling phenomena during normal cell development and differentiation. Still, the calcium signaling pathways and intracellular calcium responses to various ligands or stress conditions have not been sufficiently explored as yet in embryonic or induced pluripotent stem cells and in their differentiated offspring. This is partly due to the special culturing conditions of these cell types, the rapid morphological and functional changes in heterogeneous cell populations during early differentiation, and methodological problems in cellular calcium measurements. In this paper, we review the currently available data in the literature on calcium signaling in pluripotent stem cells and discuss the potential shortcomings of these studies. Various assay methods are surveyed for obtaining reliable data both in undifferentiated embryonic stem cells and in specific, stem cell-derived human tissues. In this paper, we present the modulation of calcium signaling in human embryonic stem cells (hESC) and in their derivates; mesenchymal stem cell like (MSCl) cells and cardiac tissues using the fluorescent calcium indicator Fluo-4 and confocal microscopy. LPA, trypsin and angiotensin II were effective in inducing calcium signals both in HUES9 and MSCl cells. Histamine and thrombin induced calcium signal exclusively in the MSCl cells, while ATP was effective only in HUES9 cells. There was no calcium signal evoked by GABA, even at relatively high concentrations. In stem cell-derived cardiomyocytes a rapid increase in the beating rate and an increase of the calcium signal peaks could be observed after the addition of adrenaline, while verapamil led to a strong decrease in cellular calcium and stopped spontaneous contractions in a relaxed state.},
	keywords = {HISTAMINE; THROMBIN; FLUORESCENCE; TRYPSIN; review; human; Cell Differentiation; priority journal; nonhuman; verapamil; Nervous System; cell culture; Adenosine Triphosphate; calcium cell level; adrenalin; Angiotensin II; CAFFEINE; cell maturation; embryonic stem cell; 4 aminobutyric acid; heart muscle cell; cell stress; Calcium Signaling; calcium mobilization; confocal microscopy; mesenchymal stem cell; Lysophosphatidic acid; pluripotent stem cell; induced pluripotent stem cell; muscle fiber contraction; Receptor-induced calcium signal; Human embryonic stem cell; Fluorescent calcium indicators},
	year = {2012},
	eissn = {1872-8057},
	pages = {57-67},
	orcid-numbers = {Pászty, Katalin/0000-0003-2457-8555; Szebényi, Kornélia/0000-0003-1558-8372; Homolya, László/0000-0003-1639-8140; Sarkadi, Balázs/0000-0003-0592-4539}
}

@article{MTMT:1934246,
	title = {Reliable transgene-independent method for determining Sleeping Beauty transposon copy numbers},
	url = {https://m2.mtmt.hu/api/publication/1934246},
	author = {Kolacsek, Orsolya and Krizsik, Virág and Schamberger, Anita and Erdei, Zsuzsa and Apáti, Ágota and Várady, György and Mátés, Lajos and Izsvák, Zsuzsa and Ivics, Zoltán and Sarkadi, Balázs and Orbán, Tamás I.},
	doi = {10.1186/1759-8753-2-5},
	journal-iso = {MOB DNA},
	journal = {MOBILE DNA},
	volume = {2},
	unique-id = {1934246},
	issn = {1759-8753},
	abstract = {Background: The transposon-based gene delivery technique is emerging as a method of choice for gene therapy. The Sleeping Beauty (SB) system has become one of the most favored methods, because of its efficiency and its random integration profile. Copy-number determination of the delivered transgene is a crucial task, but a universal method for measuring this is lacking. In this paper, we show that a real-time quantitative PCR-based, transgene-independent (qPCR-TI) method is able to determine SB transposon copy numbers regardless of the genetic cargo.
		
		Results: We designed a specific PCR assay to amplify the left inverted repeat-direct repeat region of SB, and used it together with the single-copy control gene RPPH1 and a reference genomic DNA of known copy number. The qPCR-TI method allowed rapid and accurate determination of SB transposon copy numbers in various cell types, including human embryonic stem cells. We also found that this sensitive, rapid, highly reproducible and non-radioactive method is just as accurate and reliable as the widely used blotting techniques or the transposon display method. Because the assay is specific for the inverted repeat region of the transposon, it could be used in any system where the SB transposon is the genetic vehicle.
		
		Conclusions: We have developed a transgene-independent method to determine copy numbers of transgenes delivered by the SB transposon system. The technique is based on a quantitative real-time PCR detection method, offering a sensitive, non-radioactive, rapid and accurate approach, which has a potential to be used for gene therapy.},
	year = {2011},
	eissn = {1759-8753},
	orcid-numbers = {Várady, György/0000-0003-2012-9680; Sarkadi, Balázs/0000-0003-0592-4539; Orbán, Tamás I./0000-0002-3424-3428}
}

@article{MTMT:1791527,
	title = {ABCC6 does not transport vitamin K3-glutathione conjugate from the liver: Relevance to pathomechanisms of pseudoxanthoma elasticum.},
	url = {https://m2.mtmt.hu/api/publication/1791527},
	author = {Fülöp, Krisztina and Jiang, Q and Wetering, KV and Pomozi, Viola and Szabó, Pál Tamás and Arányi, Tamás and Sarkadi, Balázs and Borst, P and Uitto, J and Váradi, András},
	doi = {10.1016/j.bbrc.2011.10.095},
	journal-iso = {BIOCHEM BIOPH RES CO},
	journal = {BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS},
	volume = {415},
	unique-id = {1791527},
	issn = {0006-291X},
	abstract = {Vitamin K is a cofactor required for gamma-glutamyl carboxylation of several proteins regulating blood clotting, bone formation and soft tissue mineralization. Vitamin K3 is an important intermediate during conversion of the dietary vitamin K1 to the most abundant vitamin K2 form. It has been suggested that ABCC6 may have a role in transporting vitamin K or its derivatives from the liver to the periphery. This activity is missing in pseudoxanthoma elasticum, a genetic disorder caused by mutations in ABCC6 characterized by abnormal soft tissue mineralization. Here we examined the efflux of the glutathione conjugate of vitamin K3 (VK3GS) from the liver in wild type and Abcc6(-/-) mice, and in transport assays in vitro. We found in liver perfusion experiments that VK3GS is secreted into the inferior vena cava, but we observed no significant difference between wild type and Abcc6(-/-) animals. We overexpressed the human ABCC6 transporter in Sf9 insect and MDCKII cells and assayed its vitamin K3-conjugate transport activity in vitro. We found no measurable transport of VK3GS by ABCC6, whereas ABCC1 transported this compound at high rate in these assays. These results show that VK3GS is not the essential metabolite transported by ABCC6 from the liver and preventing the symptoms of pseudoxanthoma elasticum.},
	year = {2011},
	eissn = {1090-2104},
	pages = {468-471},
	orcid-numbers = {Szabó, Pál Tamás/0000-0003-2260-4641; Sarkadi, Balázs/0000-0003-0592-4539}
}

@inbook{MTMT:1762755,
	title = {Use of Transposon-Transposase Systems for Stable Genetic Modification of Embryonic Stem Cells},
	url = {https://m2.mtmt.hu/api/publication/1762755},
	author = {Orbán, Tamás I. and Apáti, Ágota and Izsvák, Zsuzsa and Ivics, Zoltán and Sarkadi, Balázs},
	booktitle = {Methodological Advances in the Culture, Manipulation and Utilization of Embryonic Stem Cells for Basic and Practical Applications},
	doi = {10.5772/13843},
	unique-id = {1762755},
	year = {2011},
	pages = {259-274},
	orcid-numbers = {Orbán, Tamás I./0000-0002-3424-3428; Sarkadi, Balázs/0000-0003-0592-4539}
}

@article{MTMT:1760827,
	title = {Apical localization of PMCA2w/b is enhanced in terminally polarized MDCK cells},
	url = {https://m2.mtmt.hu/api/publication/1760827},
	author = {Antalffy, Géza and Caride, AJ and Pászty, Katalin and Hegedűs, Luca and Padányi, Rita and Strehler, EE and Enyedi, Ágnes},
	doi = {10.1016/j.bbrc.2011.05.147},
	journal-iso = {BIOCHEM BIOPH RES CO},
	journal = {BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS},
	volume = {410},
	unique-id = {1760827},
	issn = {0006-291X},
	abstract = {The "w" splice forms of PMCA2 localize to distinct membrane compartments such as the apical membrane of the lactating mammary epithelium, the stereocilia of inner ear hair cells or the post-synaptic density of hippocampal neurons. Previous studies indicated that PMCA2w/b was not fully targeted to the apical domain of MDCK cells but distributed more evenly to the lateral and apical membrane compartments. Overexpression of the apical scaffold protein NHERF2, however, greatly increased the amount of the pump in the apical membrane of these epithelial cells. We generated a stable MDCK cell line expressing non-tagged, full-length PMCA2w/b to further study the localization and function of this protein. Here we demonstrate that PMCA2w/b is highly active and shows enhanced apical localization in terminally polarized MDCK cells grown on semi-permeable filters. Reversible surface biotinylation combined with confocal microscopy of fully polarized cells show that the pump is stabilized in the apical membrane via the apical membrane cytoskeleton with the help of endogenous NHERF2 and ezrin. Disruption of the actin cytoskeleton removed the pump from the apical actin patches without provoking its internalization. Our data suggest that full polarization is a prerequisite for proper positioning of the PMCA2w variants in the apical membrane domain of polarized cells.},
	keywords = {Dogs; Animals; Humans; Transfection; Cell Line; Cell Membrane/*enzymology; Plasma Membrane Calcium-Transporting ATPases/genetics/*metabolism; Isoenzymes/genetics/metabolism; Sodium-Hydrogen Antiporter/genetics/metabolism; Phosphoproteins/genetics/metabolism; *Cell Polarity},
	year = {2011},
	eissn = {1090-2104},
	pages = {322-327},
	orcid-numbers = {Pászty, Katalin/0000-0003-2457-8555; Padányi, Rita/0000-0001-7798-0463; Enyedi, Ágnes/0000-0002-7366-9376}
}

@article{MTMT:1760813,
	title = {Tyrosine kinase inhibitors as modulators of ATP binding cassette multidrug transporters: substrates, chemosensitizers or inducers of acquired multidrug resistance?},
	url = {https://m2.mtmt.hu/api/publication/1760813},
	author = {Brózik, Anna and Hegedüs, Csilla and Erdei, Zsuzsa and Hegedűs, Tamás and Laczka, Csilla and Szakács, Gergely and Sarkadi, Balázs},
	doi = {10.1517/17425255.2011.562892},
	journal-iso = {EXPERT OPIN DRUG MET},
	journal = {EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY},
	volume = {7},
	unique-id = {1760813},
	issn = {1742-5255},
	abstract = {INTRODUCTION: Anticancer tyrosine kinase inhibitors (TKIs) are small molecule hydrophobic compounds designed to arrest aberrant signaling pathways in malignant cells. Multidrug resistance (MDR) ATP binding cassette (ABC) transporters have recently been recognized as important determinants of the general ADME-Tox (absorption, distribution, metabolism, excretion, toxicity) properties of small molecule TKIs, as well as key factors of resistance against targeted anticancer therapeutics. AREAS COVERED: The article summarizes MDR-related ABC transporter interactions with imatinib, nilotinib, dasatinib, gefitinib, erlotinib, lapatinib, sunitinib and sorafenib, including in vitro and in vivo observations. An array of methods developed to study such interactions is presented. Transporter-TKI interactions relevant to the ADME-Tox properties of TKI drugs, primary or acquired cancer TKI resistance, and drug-drug interactions are also reviewed. EXPERT OPINION: Based on the concept presented in this review, TKI anticancer drugs are considered as compounds recognized by the cellular mechanisms handling xenobiotics. Accordingly, novel anticancer therapies should equally focus on the effectiveness of target inhibition and exploration of potential interactions of the designed molecules by membrane transporters. Thus, targeted hydrophobic small molecule compounds should also be screened to evade xenobiotic-sensing cellular mechanisms.},
	keywords = {Animals; Humans; Drug Delivery Systems; Hydrophobic and Hydrophilic Interactions; Neoplasms/drug therapy/pathology; Drug Resistance, Neoplasm; Protein-Tyrosine Kinases/*antagonists & inhibitors; Protein Kinase Inhibitors/adverse effects/pharmacokinetics/*pharmacology; Antineoplastic Agents/adverse effects/pharmacokinetics/*pharmacology; ATP-Binding Cassette Transporters/drug effects},
	year = {2011},
	eissn = {1744-7607},
	pages = {623-642},
	orcid-numbers = {Hegedűs, Tamás/0000-0002-0331-9629; Sarkadi, Balázs/0000-0003-0592-4539}
}

@article{MTMT:1760812,
	title = {ABC transporters affect the detection of intracellular oxidants by fluorescent probes.},
	url = {https://m2.mtmt.hu/api/publication/1760812},
	author = {Prochazkova, J and Kubala, L and Kotasova, H and Gudernova, I and Sramkova, Z and Pekarova, M and Sarkadi, Balázs and Pachernik, J},
	doi = {10.3109/10715762.2011.579120},
	journal-iso = {FREE RADIC RES},
	journal = {FREE RADICAL RESEARCH},
	volume = {45},
	unique-id = {1760812},
	issn = {1071-5762},
	abstract = {Intracellular production of reactive oxygen species (ROS) plays an important role in the control of cell physiology. For the assessment of intracellular ROS production, a plethora of fluorescent probes is commonly used. Interestingly, chemical structures of these probes imply they could be substrates of plasma membrane efflux pumps, called ABC transporters. This study tested whether the determination of intracellular ROS production and mitochondrial membrane potential by selected fluorescent probes is modulated by the expression and activity of ABC transporters. The sub-clones of the HL-60 cell line over-expressing MDR1, MRP1 and BCRP transporters were employed. ROS production measured by luminol- and L-012-enhaced chemiluminescence and cytochrome c reduction assay showed similar levels of ROS production in all the employed cell lines. It was proved that dihydrorhodamine 123, dihexiloxocarbocyanine iodide, hydroethidine, tetrachloro-tetraethylbenzimidazolocarbo-cyanine iodide and tetramethylrhodamine ethyl ester perchlorate are substrates for MDR1; dichlorodihydrofluoresceine, hydroethidine and tetramethylrhodamine ethyl ester perchlorate are substrates for MRP1; dichlorodihydrofluoresceine, dihydrorhodamine 123, hydroethidine and tetrachloro-tetraethylbenzimidazolocarbo-cyanine iodide are substrates for BCRP. Thus, the determination of intracellular ROS and mitochondrial potential by the selected probes is significantly altered by ABC transporter activities. The activity of these transporters must be considered when employing fluorescent probes for the assessment of ROS production or mitochondrial membrane potential.},
	year = {2011},
	eissn = {1029-2470},
	pages = {779-787},
	orcid-numbers = {Sarkadi, Balázs/0000-0003-0592-4539}
}