dc.contributor.author | Kazlauskas, Arūnas | |
dc.contributor.author | Darinskas, Adas | |
dc.contributor.author | Meškys, Rolandas | |
dc.contributor.author | Tamašauskas, Arimantas | |
dc.contributor.author | Urbonavičius, Jaunius | |
dc.date.accessioned | 2023-09-18T17:43:44Z | |
dc.date.available | 2023-09-18T17:43:44Z | |
dc.date.issued | 2019 | |
dc.identifier.issn | 1471-2407 | |
dc.identifier.uri | https://etalpykla.vilniustech.lt/handle/123456789/125622 | |
dc.description.abstract | Background: The cytosine deaminase (CD)/5-fluorocytosine (5-FC) system is among the best explored enzyme/prodrug systems in the field of the suicide gene therapy. Recently, by the screening of the environmental metagenomic libraries we identified a novel isocytosine deaminase (ICD), termed Vcz, which is able of specifically converting a prodrug 5-fluoroisocytosine (5-FIC) into toxic drug 5-fluorouracil (5-FU). The aim of this study is to test the applicability of the ICD Vcz / 5-FIC pair as a potential suicide gene therapy tool. Methods: Vcz-expressing human glioblastoma U87 and epithelial colorectal adenocarcinoma Caco-2 cells were treated with 5-FIC, and the Vcz-mediated cytotoxicity was evaluated by performing an MTT assay. In order to examine anti-tumor effects of the Vcz/5-FIC system in vivo, murine bone marrow-derived mesenchymal stem cells (MSC) were transduced with the Vcz-coding lentivirus and co-injected with 5-FIC or control reagents into subcutaneous GL261 tumors evoked in C57/BL6 mice. Results: 5-FIC alone showed no significant toxic effects on U87 and Caco-2 cells at 100 μM concentration, whereas the number of cells of both cell lines that express Vcz cytosine deaminase gene decreased by approximately 60% in the presence of 5-FIC. The cytotoxic effects on cells were also induced by media collected from Vcz-expressing cells pre-treated with 5-FIC. The co-injection of the Vcz-transduced mesenchymal stem cells and 5-FIC have been shown to augment tumor necrosis and increase longevity of tumorized mice by 50% in comparison with control group animals. Conclusions: We have confirmed that the novel ICD Vcz together with the non-toxic prodrug 5-FIC has a potential of being a new enzyme/prodrug system for suicide gene therapy. | eng |
dc.format | PDF | |
dc.format.extent | p. 1-11 | |
dc.format.medium | tekstas / txt | |
dc.language.iso | eng | |
dc.relation.isreferencedby | PubMed | |
dc.relation.isreferencedby | Scopus | |
dc.relation.isreferencedby | Science Citation Index Expanded (Web of Science) | |
dc.title | Isocytosine deaminase Vcz as a novel tool for the prodrug cancer therapy | |
dc.type | Straipsnis Web of Science DB / Article in Web of Science DB | |
dcterms.references | 40 | |
dc.type.pubtype | S1 - Straipsnis Web of Science DB / Web of Science DB article | |
dc.contributor.institution | Lietuvos sveikatos mokslų universitetas | |
dc.contributor.institution | Nacionalinis vėžio institutas | |
dc.contributor.institution | Vilniaus universitetas | |
dc.contributor.institution | Vilniaus universitetas Vilniaus Gedimino technikos universitetas | |
dc.contributor.faculty | Fundamentinių mokslų fakultetas / Faculty of Fundamental Sciences | |
dc.subject.researchfield | M 001 - Medicina / Medicine | |
dc.subject.researchfield | N 004 - Biochemija / Biochemistry | |
dc.subject.researchfield | T 005 - Chemijos inžinerija / Chemical engineering | |
dc.subject.researchfield | T 008 - Medžiagų inžinerija / Material engineering | |
dc.subject.vgtuprioritizedfields | FM0202 - Ląstelių ir jų biologiškai aktyvių komponentų tyrimai / Investigations on cells and their biologically active components | |
dc.subject.ltspecializations | L105 - Sveikatos technologijos ir biotechnologijos / Health technologies and biotechnologies | |
dc.subject.en | 5-fluoroisocytosine | |
dc.subject.en | 5-fluorouracil | |
dc.subject.en | Cancer therapy | |
dc.subject.en | Isocytosine deaminase | |
dc.subject.en | Prodrug-activation system | |
dcterms.sourcetitle | BMC Cancer | |
dc.description.issue | no. 1 | |
dc.description.volume | vol. 19 | |
dc.publisher.name | BioMed Central Ltd. | |
dc.publisher.city | London | |
dc.identifier.doi | 2-s2.0-85062419016 | |
dc.identifier.doi | 85062419016 | |
dc.identifier.doi | 0 | |
dc.identifier.doi | KMU02-000097768 | |
dc.identifier.doi | 30832616 | |
dc.identifier.doi | 000460510100004 | |
dc.identifier.doi | 1 | |
dc.identifier.doi | 10.1186/s12885-019-5409-7 | |
dc.identifier.elaba | 34996808 | |