title: Tumor radiosensitization by gene therapy against endoglin.
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.
authors.affiliation: Department of Experimental Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia.
authors.forename: M
authors.initials: M
authors.lastname: Stimac
authors.affiliation: Department of Experimental Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia.
authors.forename: U
authors.identifier: 0000-0002-0481-4226
authors.initials: U
authors.lastname: Kamensek
authors.affiliation: Department of Experimental Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia.|Faculty of Health Sciences, University of Primorska, Izola, Slovenia.
authors.forename: M
authors.initials: M
authors.lastname: Cemazar
authors.affiliation: Department of Experimental Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia.
authors.forename: S
authors.initials: S
authors.lastname: Kranjc
authors.affiliation: Faculty of Health Sciences, University of Primorska, Izola, Slovenia.
authors.forename: A
authors.initials: A
authors.lastname: Coer
authors.affiliation: Department of Experimental Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia.
authors.forename: G
authors.initials: G
authors.lastname: Sersa
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D000071063:Endoglin / Q000235:genetics* / Q000378:metabolism; D005260:Female; D055785:Gene Knockdown Techniques; D015316:Genetic Therapy; D015674:Mammary Neoplasms, Animal / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D034741:RNA, Small Interfering / Q000235:genetics; D011836:Radiation Tolerance; D047368:Tumor Burden / Q000528:radiation effects
chemical_list: D000071063:Endoglin; C502004:Eng protein, mouse; D034741:RNA, Small Interfering