J Cancer 2014; 5(5):368-381. doi:10.7150/jca.9147

Research Paper

Safety and Efficacy of Suicide Gene Therapy with Adenosine Deaminase 5-Fluorocytosine Silmutaneously in in Vitro Cultures of Melanoma and Retinal Cell Lines

Antonios Sakkas1, Paul Zarogoulidis1✉, Kalliopi Domvri1, Wolfgang Hohenforst-Schmidt2, Dimitris Bougiouklis3, Stylianos Kakolyris4, Thomas Zarampoukas1, Ioannis Kioumis1, Georgia Pitsiou1, Haidong Huang5, Qiang Li5, Soultana Meditskou6, Theodora Tsiouda7, Nikolaos Pezirkianidis8, Konstantinos Zarogoulidis1

1. Pulmonary Department-Oncology Unit, ``G. Papanikolaou`` General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
2. II Medical Department, ``Coburg`` Regional Clinic, Coburg, Germany.
3. Gene and Cell Therapy Center, Hematology-BMT Unit, ``G. Papanikolaou`` Hospital, Thessaloniki, Greece.
4. Oncology Department, University General Hospital of Alexandroupolis, Alexandroupolis, Greece.
5. Department of Respiratory Diseases, Changhai Hospital/First Affiliated Hospital of the Second Military Medical University, Shanghai, People's Republic of China.
6. Laboratory of Histology, Embryology and Anthropology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
7. Internal Medicine Department, ``Theiageneio`` Anticancer Hospital, Thessaloniki, Greece.
8. Surgery Department, Private Cabinet, Serres, Greece.

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.

Keywords: suicide gene therapy, 5-fluorocytosine, melanoma, retinal.

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How to cite this article:
Sakkas A, Zarogoulidis P, Domvri K, Hohenforst-Schmidt W, Bougiouklis D, Kakolyris S, Zarampoukas T, Kioumis I, Pitsiou G, Huang H, Li Q, Meditskou S, Tsiouda T, Pezirkianidis N, Zarogoulidis K. Safety and Efficacy of Suicide Gene Therapy with Adenosine Deaminase 5-Fluorocytosine Silmutaneously in in Vitro Cultures of Melanoma and Retinal Cell Lines. J Cancer 2014; 5(5):368-381. doi:10.7150/jca.9147. Available from http://www.jcancer.org/v05p0368.htm