title: Local bystander effect induces dormancy in human medullary thyroid carcinoma model in vivo.
abstract: The extent of local bystander effect induced by fusion yeast cytosine deaminase::uracil phosphoribosyltransferase (yCD) in combination with 5-fluorocytosine (5FC) was evaluated in xenogeneic model of human medullary thyroid carcinoma (MTC). This approach to gene-directed enzyme/prodrug therapy (GDEPT) induces strong bystander cytotoxicity. Effector yCD-TT mixed with target EGFP-TT cells in a ratio 2:9 could achieve significant tumor regression and 14-fold decrease in serum marker calcitonin upon 5FC administration. Histopathological analysis unraveled that antitumor effect resulted in tumor dormancy and proliferation arrest of remaining tumor cell clusters in vivo. yCD/5FC combination represents another GDEPT approach to achieve tumor growth control in MTC.
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: Lucia
authors.initials: L
authors.lastname: Feketeova
authors.forename: Miroslava
authors.initials: M
authors.lastname: Matuskova
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Kozovska
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; D024201:Bystander Effect / Q000187:drug effects*; D002116:Calcitonin / Q000097:blood; D018278:Carcinoma, Neuroendocrine; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D043525:Cytosine Deaminase / Q000494:pharmacology*; D005260:Female; D005437:Flucytosine / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010430:Pentosyltransferases / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D013964:Thyroid Neoplasms / Q000188:drug therapy*; D023041:Xenograft Model Antitumor Assays
chemical_list: D011993:Recombinant Fusion Proteins; D002116:Calcitonin; D005437:Flucytosine; D010430:Pentosyltransferases; C023269:uracil phosphoribosyltransferase; D043525:Cytosine Deaminase