Reference : Sufasalazine unveils a contact-independent HSV-TK/ganciclovir gene therapy bystander eff...
Scientific journals : Article
Human health sciences : Oncology
http://hdl.handle.net/2268/62712
Sufasalazine unveils a contact-independent HSV-TK/ganciclovir gene therapy bystander effect in malignant gliomas
English
Robe, Pierre mailto [Université de Liège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques >]
Nguyen-Khac, Minh-Tuan [Université de Liège - ULg > Département des sciences cliniques > Neurochirurgie >]
Lambert, Frédéric mailto [Centre Hospitalier Universitaire de Liège - CHU > > Génétique >]
Lechanteur, Chantal mailto [Centre Hospitalier Universitaire de Liège - CHU > > Hématologie clinique >]
Jolois, Olivier mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Histologie humaine >]
Ernst-Gengoux, P. [> > > >]
Rogister, Bernard mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biochimie et physiologie générales, et biochimie humaine >]
Bours, Vincent mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Génétique générale et humaine]
Jan-2007
International Journal of Oncology
Professor D A Spandidos
30
1
283-290
Yes
International
1019-6439
Athens
[en] glioma ; gene therapy ; Sulfasalazine ; thymidine kinase ; ganciclovir ; bystander effect
[en] The efficacy of HSV-TK/ganciclovir-based gene therapy on malignant gliomas largely relies on the amplitude of the bystander effect. In these experiments, the anti-inflammatory drug Sulfasalazine increased the HSV-TK/ganciclovir bystander effect in C6, 9L and LN18 cells but not in U87 glioma cells. Using bi-compartmental culture devices and conditioned medium transfer experiments, we showed that in C6, 9L and LN18 cells but not in U87 cells, Sulfasalazine also unveiled a new, contact-independent mechanism of HSV-TK/ganciclovir bystander effect. Upon treatment with ganciclovir, human LN18-TK but not U87-TK cells synthetized and released TNF-alpha in the culture medium. Sulfasalazine sensitized glioma cells to the toxic effect of TNF-alpha. and enhanced its secretion in LN18-TK cells in response to GCV treatment. The caspase-8 inhibitor Z-IETD-FMK and a blocking antibody to TNF-alpha both inhibited the contact-independent bystander effect in LN18 cells. Taken together, these results suggest that TNF-alpha mediates the contact-independent bystander effect in LN18 cells. The treatment with GCV and/or Sulfasalazine of tumor xenografts consisting of a mix of 98% C6 and 2% C6-TK cells shows that Sulfasalazine is also a potent adjunct to the in vivo treatment of gliomas.
http://hdl.handle.net/2268/62712

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