20.500.12556/RUL-155597 Tumor radiosensitization by gene electrotransfer-mediated double targeting of tumor vasculature Targeting the tumor vasculature through specific endothelial cell markers involved in different signaling pathways represents a promising tool for tumor radiosensitization. Two prominent targets are endoglin (CD105), a transforming growth factor β co-receptor, and the melanoma cell adhesion molecule (CD1046), present also on many tumors. In our recent in vitro study, we constructed and evaluated a plasmid for simultaneous silencing of these two targets. In the current study, our aim was to explore the therapeutic potential of gene electrotransfer-mediated delivery of this new plasmid in vivo, and to elucidate the effects of combined therapy with tumor irradiation. The antitumor effect was evaluated by determination of tumor growth delay and proportion of tumor free mice in the syngeneic murine mammary adenocarcinoma tumor model TS/A. Histological analysis of tumors (vascularization, proliferation, hypoxia, necrosis, apoptosis and infiltration of immune cells) was performed to evaluate the therapeutic mechanisms. Additionally, potential activation of the immune response was evaluated by determining the induction of DNA sensor STING and selected pro-inflammatory cytokines using qRT-PCR. The results point to a significant radiosensitization and a good therapeutic potential of this gene therapy approach in an otherwise radioresistant and immunologically cold TS/A tumor model, making it a promising novel treatment modality for a wide range of tumors. gene electrotransfer adenocarcinom radiosensitization silencing plasmid antivascular shRNA CD105 CD1046 DNA sensors murine mammary adenocarcinoma TS/A genski elektroprenos adenokarcinom radiosensitizacija true false true Angleški jezik Slovenski jezik Članek v reviji 2024-04-08 10:05:50 2024-04-08 10:05:55 2024-04-09 03:46:01 0000-00-00 00:00:00 2023 0 0 14 str. iss. 3, art. 2755 Vol. 24 2023 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 602 1422-0067 10.3390/ijms24032755 140588547 ijms-24-02755-v2.pdf ijms-24-02755-v2.pdf 1 BE54801510FDF1DEC54EB400AE854E66 a40c89a59438f515049f8535fd3d8e26c53cd26f4265ede446453d8eaca671a2 32db4943-f57f-11ee-937a-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=182564 https://www.mdpi.com/1422-0067/24/3/2755 1 d3f72c40-f57e-11ee-937a-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=182563 Zdravstvena fakulteta Medicinska fakulteta Biotehniška fakulteta 0 0 0