Endoglin (CD105), a TGF-β co-receptor, and endothelin-1, a vasoconstrictor peptide, are both overexpressed in tumor endothelial and melanoma cells. Their targeting is therefore a promising therapeutic approach for melanoma tumors. The aim of our study was to construct an eukaryotic expression plasmid encoding the shRNA molecules against CD105 under the control of endothelin-1 promoter and to evaluate its therapeutic potential both in vitro in murine B16F10-luc melanoma and SVEC4-10 endothelial cells and in vivo in mice bearing highly metastatic B16F10-luc tumors. Plasmid encoding shRNA against CD105 under the control of constitutive U6 promoter was used as a control. We demonstrated the antiproliferative and antiangiogenic effects of both plasmids in SVEC4-10 cells, as well as a moderate antitumor and pronounced antimetastatic effect in B16F10-luc tumors in vivo. Our results provide evidence that targeting melanoma with shRNA molecules against CD105 under the control of endothelin-1 promoter is a feasible and effective treatment, especially for the prevention of metastatic spread.
COBISS.SI-ID: 1537399748
In this focused review we aimed at deepening the understanding of different principles of drug (electrochemotherapy) and gene delivery (gene electrotransfer) by electroporation and then propose a concept for their combination. Namely although electrochemotherapy is successfully used for tumor treatment with local effectiveness up to 80% of local tumor control, there is no noticeable effect on metastases. To increase systemic antitumor effectiveness of electrochemotherapy, electrotransfer of genes with immunomodulatory effect (immunogene electrotransfer) could be used as adjuvant treatment. Since electrochemotherapy can induce immunogenic cell death, adjuvant immunogene electrotransfer to peritumoral tissue could lead to locoregional effect as well as the abscopal effect on distant untreated metastases. As a proof of principle we therefore propose a combination of electrochemotherapy boosted by peritumoral IL-12 electrotransfer as in situ vaccination for successful tumor treatment. The topic of the paper is relevant for cancer treatment, particularly for cancer immunotherapy.
COBISS.SI-ID: 2044027
Electroporation allows efficient delivery of DNA into cells and tissues, thereby improving the expression of therapeutic or immunogenic proteins that are encoded by plasmid DNA. This simple and versatile method holds a great potential and could address unmet medical needs such as the prevention or treatment of many cancers or infectious diseases. This review explores the electroporation mechanism and the parameters affecting its efficacy. An analysis of past and current clinical trials focused on DNA electroporation is presented. The pathologies addressed, the protocol used, the treatment outcome and the tolerability are highlighted. In addition, several of the possible optimization strategies for improving patient compliance and therapeutic efficacy are discussed such as plasmid design, use of genetic adjuvants for DNA vaccines, choice of appropriate delivery site and electrodes as well as pulse parameters. The growing number of clinical trials and the results already available underline the strong potential of DNA electroporation which combines both safety and efficiency. Nevertheless, it remains critical to further increase fundamental knowledge to refine future strategies, to develop concerted and common DNA electroporation protocols and to continue exploring new electroporation-based therapeutic options.
COBISS.SI-ID: 2184571
Electroporation-based treatments provide highly effective local treatment for a variety of tumors. For deep seated tumors in the head and neck region, the complex anatomy and difficult access often warrants the use of single long needle electrodes for which a treatment plan provides the information on optimal voltages and electrode positions in the highly constrained environment. The feasibility of such treatments can be enhanced by use of a navigation system for the positioning of electrodes. Treatment planning is performed using finite element method to compute electric fields in the tumor and surrounding tissues and using this to optimize delivered voltages. Navigation systems consist of optical tracking system, which tracks an instrument in space to introduce it along predefined trajectories. This paper aims to present a technical method for coupling treatment planning with a navigation device and using that to treat tumors in the head and neck area illustrated with a case of electrochemotherapy treatment of tumors in the neck and in the left parotid gland.
COBISS.SI-ID: 11129684
Dielectric properties of freshly excised human liver tissues (in vitro) with several pathological conditions including cancer were obtained in frequency range 100 MHz-5 GHz. Differences in dielectric behavior of normal and pathological tissues at microwave frequencies are discussed based on histological information for each tissue. Data presented are useful for many medical applications, in particular nanosecond pulsed electroporation techniques. Knowledge of dielectric properties is vital for mathematical calculations of local electric field distribution inside electroporated tissues and can be used to optimize the process of electroporation for treatment planning procedures.
COBISS.SI-ID: 2213755