Safety and efficacy of suicide gene therapy with adenosine deaminase 5-fluorocytosine silmutaneously in in vitro cultures of melanoma and retinal cell lines.

Abstract

Local treatment as a treatment modality is gaining increased general acceptance over time. Novel drugs and methodologies of local administration are being investigated in an effort to achieve disease local control. Suicide gene therapy is a method that has been investigated as a local treatment with simultaneously distant disease control. In our current experiment we purchased HTB-70 (melanoma cell line, derived from metastatic axillary node) and CRL-2302 (human retinal epithelium) were from ATCC LGC Standards and Ancotil(®), 2.5 g/250 ml (1 g/00ml) (5-Flucytosine) MEDA; Pharmaceuticals Ltd. UK. Adenosine Cytosine Deaminase (Ad.CD) was also used in order to convert the pro-drug 5-Flucytosine to the active 5-Fluoracil. Three different concentrations of 5-Flucytosine (5-FC) were administered (0.2ml, 0.8ml and 1.2ml). At indicated time-points (4h, 8h and 24h) cell viability and apoptosis were measured. Our concept was to investigate whether suicide gene therapy with Ad. CD-5-FC could be used with safety and efficiency as a future local treatment for melanoma located in the eye cavity. Indeed, our results indicated that in every 5-FC administration had mild cytotoxicity for the retinal cells, while increased apoptosis was observed for the melanoma cell line.

• Authors: Antonios Sakkas, Paul Zarogoulidis, Kalliopi Domvri, Wolfgang Hohenforst-Schmidt, Dimitris Bougiouklis, Stylianos Kakolyris, Thomas Zarampoukas, Ioannis Kioumis, Georgia Pitsiou, Haidong Huang, Qiang Li, Soultana Meditskou, Theodora Tsiouda, Nikolaos Pezirkianidis, Konstantinos Zarogoulidis
• Journal: Journal of Cancer (J Cancer) Vol. 5 Issue 5 Pg. 368-81 ( 2014) ISSN: 1837-9664 [Print] Australia
• PMID: 24799955 (Publication Type: Journal Article)