Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/79522
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dc.contributor.author | Lim, S. | - |
dc.contributor.author | Kumar, R. | - |
dc.contributor.author | Akkamsetty, Y. | - |
dc.contributor.author | Wang, W. | - |
dc.contributor.author | Ho, K. | - |
dc.contributor.author | Neilsen, P. | - |
dc.contributor.author | Walther, D. | - |
dc.contributor.author | Suetani, R. | - |
dc.contributor.author | Prestidge, C. | - |
dc.contributor.author | Callen, D. | - |
dc.date.issued | 2013 | - |
dc.identifier.citation | BMC Cancer, 2013; 13(113):1-11 | - |
dc.identifier.issn | 1471-2407 | - |
dc.identifier.issn | 1471-2407 | - |
dc.identifier.uri | http://hdl.handle.net/2440/79522 | - |
dc.description | Extent: 11 p. | - |
dc.description.abstract | BACKGROUND: Despite the potential of improving the delivery of epigenetic drugs, the subsequent assessment of changes in their epigenetic activity is largely dependent on the availability of a suitable and rapid screening bioassay. Here, we describe a cell-based assay system for screening gene reactivation. METHODS: A cell-based assay system (EPISSAY) was designed based on a silenced triple-mutated bacterial nitroreductase TMnfsB fused with Red-Fluorescent Protein (RFP) expressed in the non-malignant human breast cell line MCF10A. EPISSAY was validated using the target gene TXNIP, which has previously been shown to respond to epigenetic drugs. The potency of a epigenetic drug model, decitabine, formulated with PEGylated liposomes was also validated using this assay system. RESULTS: Following treatment with DNA methyltransferase (DNMT) and histone deacetylase (HDAC) inhibitors such as decitabine and vorinostat, increases in RFP expression were observed, indicating expression of RFP-TMnfsB. The EPISSAY system was then used to test the potency of decitabine, before and after PEGylated liposomal encapsulation. We observed a 50% higher potency of decitabine when encapsulated in PEGylated liposomes, which is likely to be due to its protection from rapid degradation. CONCLUSIONS: The EPISSAY bioassay system provides a novel and rapid system to compare the efficiencies of existing and newly formulated drugs that reactivate gene expression. | - |
dc.description.statementofresponsibility | Sue Ping Lim, Raman Kumar, Yamini Akkamsetty, Wen Wang, Kristen Ho, Paul M. Neilsen, Diego J. Walther, Rachel J. Suetani, Clive Prestidge and David F. Callen | - |
dc.language.iso | en | - |
dc.publisher | BioMed Central Ltd. | - |
dc.relation.isreplacedby | 2440/90436 | - |
dc.relation.isreplacedby | http://hdl.handle.net/2440/90436 | - |
dc.rights | © 2013 Lim et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the CreativeCommons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, andreproduction in any medium, provided the original work is properly cited. | - |
dc.source.uri | http://dx.doi.org/10.1186/1471-2407-13-113 | - |
dc.subject | Cell-based assay system | - |
dc.subject | decitabine | - |
dc.subject | liposomes | - |
dc.subject | nanotechnology | - |
dc.subject | CB1954 | - |
dc.subject | nitroreductase | - |
dc.title | Development of a novel cell-based assay system EPISSAY for screening epigenetic drugs and liposome formulated decitabine | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1186/1471-2407-13-113 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Kumar, R. [0000-0001-7976-8386] | - |
dc.identifier.orcid | Callen, D. [0000-0002-6189-9991] | - |
Appears in Collections: | Aurora harvest 7 Medicine publications |
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hdl_79522.pdf | Published version | 604.37 kB | Adobe PDF | View/Open |
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