title: Bystander cytotoxicity in human medullary thyroid carcinoma cells mediated by fusion yeast cytosine deaminase and 5-fluorocytosine.
abstract: In our work, we have evaluated efficiency of gene-directed enzyme/prodrug therapy (GDEPT) based on combination of fusion yeast cytosine deaminase (yCD) and 5-fluorocytosine (5FC) on model human medullary thyroid carcinoma (MTC) cell line TT. We determined the efficiency of this GDEPT approach in suicide and bystander cytotoxicity induction. We have shown significant bystander effect in vitro and 5FC administration resulted in potent antitumor effect in vivo. Furthermore, we have unraveled high efficiency of cell-mediated GDEPT, when human mesenchymal stromal cells (MSC) were used as delivery vehicles in direct cocultures in vitro. Nevertheless, effector MSC exhibited inhibitory effect on TT cell proliferation and abrogated TT xenotransplant growth in vivo. We suggest that yCD/5FC combination represents another experimental treatment modality to be tested in MTC and our data further support the exploration of MSC antitumor potential for future use in metastatic MTC therapy.
authors.affiliation: Laboratory of Molecular Oncology, Cancer Research Institute, Slovak Academy of Sciences, Vlarska 7, 833 91 Bratislava, Slovakia. exonkuce@savba.sk
authors.forename: Lucia
authors.initials: L
authors.lastname: Kucerova
authors.forename: Miroslava
authors.initials: M
authors.lastname: Matuskova
authors.forename: Kristina
authors.initials: K
authors.lastname: Hlubinova
authors.forename: Roman
authors.initials: R
authors.lastname: Bohovic
authors.forename: Lucia
authors.initials: L
authors.lastname: Feketeova
authors.forename: Pavol
authors.initials: P
authors.lastname: Janega
authors.forename: Pavel
authors.initials: P
authors.lastname: Babal
authors.forename: Martina
authors.initials: M
authors.lastname: Poturnajova
mesh_terms: D000818:Animals; D018278:Carcinoma, Neuroendocrine; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D043525:Cytosine Deaminase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005437:Flucytosine / Q000493:pharmacokinetics / Q000494:pharmacology*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011897:Random Allocation; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D014161:Transduction, Genetic / Q000379:methods; D023041:Xenograft Model Antitumor Assays
chemical_list: D005437:Flucytosine; D043525:Cytosine Deaminase