title: Tomato thymidine kinase-based suicide gene therapy for malignant glioma--an alternative for Herpes Simplex virus-1 thymidine kinase.
abstract: Malignant gliomas (MGs) are the most common malignant primary brain tumors with a short life estimate accompanied by a marked reduction in the quality of life. Herpes Simplex virus-1 thymidine kinase ganciclovir (HSV-TK/GCV) system is the best characterized enzyme prodrug therapy in use. However, lipophobicity of GCV and low enzymatic activity of HSV-TK reduce the treatment efficacy. Tomato TK (ToTK) has shown high activity in combination with its specific substrate azidothymidine (AZT). The aim of this study was to evaluate whether ToTK/AZT could be used as an alternative to HSV-TK/GCV therapy. Both treatments demonstrated cytotoxicity in human MG cells in vitro. In vivo, both treatments decreased tumor growth and tumors were smaller in comparison with controls in mouse orthotopic MG model. Survival of ToTK/AZT-treated mice was significantly increased compared with control mice (*P<0.05) but not as compared with HSV-TK/GCV-treated mice. No significant differences were observed in clinical chemistry safety analyses. We conclude that both treatments showed a beneficial treatment response in comparison to controls on tumor growth and ToTK/AZT also on survival. There were no significant differences between these treatments. Therefore ToTK/AZT could be considered as an alternative treatment option for MG because of its favorable therapeutic characteristics.
authors.affiliation: Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
authors.forename: H
authors.initials: H
authors.lastname: Stedt
authors.affiliation: Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
authors.forename: H
authors.initials: H
authors.lastname: Samaranayake
authors.affiliation: Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
authors.forename: J
authors.initials: J
authors.lastname: Kurkipuro
authors.affiliation: Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
authors.forename: G
authors.initials: G
authors.lastname: Wirth
authors.affiliation: Department of Biology, Lund University, Lund, Sweden.
authors.forename: L S
authors.initials: LS
authors.lastname: Christiansen
authors.affiliation: Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
authors.forename: T
authors.initials: T
authors.lastname: Vuorio
authors.affiliation: 1] Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland [2] Movet Oy, Kuopio, Finland.
authors.forename: A-M
authors.initials: AM
authors.lastname: Määttä
authors.affiliation: Department of Biology, Lund University, Lund, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Piškur
authors.affiliation: 1] Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland [2] Science Service Center, Kuopio University Hospital, Kuopio, Finland [3] Gene Therapy Unit, Kuopio University Hospital, Kuopio, Finland.
authors.forename: S
authors.initials: S
authors.lastname: Ylä-Herttuala
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D041722:Genes, Transgenic, Suicide; D015316:Genetic Therapy; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D018259:Herpesvirus 1, Human / Q000201:enzymology; D006801:Humans; D018551:Solanum lycopersicum / Q000201:enzymology*; D008297:Male; D008819:Mice, Nude; D010940:Plant Proteins / Q000235:genetics*; D051381:Rats; D013937:Thymidine Kinase / Q000235:genetics*; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays; D015215:Zidovudine / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D010940:Plant Proteins; D015215:Zidovudine; D013937:Thymidine Kinase