Author/Editor		Savarin, Monika; Kamenšek, Urška; Čemažar, Maja; Kranjc, Simona; Cör, Andrej; Serša, Gregor
Title		Tumor radiosensitization by gene therapy against endoglin
Type		članek
Vol. and No.		Letnik 23, št. 7
Publication year		2016
Volume		str. 214-220
ISSN		0929-1903 - Cancer gene therapy
Language		eng
Abstract		Gene electrotransfer of plasmid encoding shRNA against endoglin exerts antitumor efficacy, predominantly by vascular targeted effect. As vascular targeting therapies can promote radiosensitization, the aim of this study was to explore this gene therapy approach with single and split dose of irradiation in an endoglin non-expressing TS/A mammary adenocarcinoma tumor model to specifically study the vascular effects. Intratumoral gene electrotransfer of plasmids encoding shRNA against endoglin, under the control of a constitutive or tissue-specific promoter for endothelial cells, combined with a single or three split doses of irradiations was evaluated for the antitumor efficacy and histologically. Both plasmids proved to be equally effective in tumor radiosensitization with 40-47% of tumor cures. The combined treatment induced a significant decrease in the number of blood vessels and proliferating cells, and an increase in levels of necrosis, apoptosis and hypoxia; therefore, the antitumor efficacy was ascribed to the interaction of vascular targeted effect of gene therapy with irradiation. Endoglin silencing by the shRNA technology, combined with electrotransfer and the use of a tissue-specific promoter for endothelial cells, proved to be a feasible and effective therapeutic approach that can be used in combined treatment with tumor irradiation.
Keywords		endoglin genski elektroprenos radiosensitizacija gensko zdravljenje radiosensitization gene electrotransfer gene therapy endoglin