Avtor/Urednik | Grošel, Alenka | |
Naslov | Vpliv kombinacije elektrogenske terapije S p53 in elektrokemoterapije s cisplatinom na humane karcinomske celične linije in mišje sarkome | |
Tip | monografija | |
Kraj izdaje | Ljubljana | |
Založnik | Univerza v Ljubljani, Medicinska fakulteta | |
Leto izdaje | 2005 | |
Obseg | str. 139 | |
Jezik | slo | |
Abstrakt | Electroporation is frequently used for permeabilisation of cells and delivery of nonpermeant molecules info cells in vitro. This allows ions, small molecules, chemotherapeutics and macromolecules to directly enter cifosol. Electroporation has been proven to be a successful method for delivery of hydrophilic drugs such as cisplatin in vitro and in vivo into various tissues, including tumours. Combination of electric pulses and chemotherapy is called electrochemotherapy. With application of electric pulses we are able to introduce genes into cells in vitro and in vivo. Electrically mediated gene therapy is called electrogene therapy. This PhD's thesis examines the cytotoxic effect of electrogene therapy with the p53 gene in combination with electrochemotherapy with cisplatin in vitro in four human carcinoma cell lines and antitumour effectiveness of this combined therapy in mouse sarcomas in vivo. Using the selected electroporation parameters in either the electrogene therapy or electrochemotherapy, we showed that cells were successfully permeabilised as determined by measuring the fluorescence of propidium iodide on a flow cytometer. The sensitivity of the cells to electrochemotherapy with cisplatin was determined by clonogenic assay. Electrochemotherapy with cisplatin had a cytotoxic effect on human carcinoma cell lines. The effect was the most pronounced on PC-3 cell line and least pronounced on the DU145 cell line. From the survival curves we determined ICso, which we used in the next part of the study. The cytotoxic effect of electrogene therapy with thep53 gene on human carcinoma cells in vitro demonstrated that prostate cancer cell lines were more sensitive to the electrogene therapy with p53 compared to the colon cancer cell lines. We established that the cytotoxic effect of electric pulses and p`3 was synergistic and p53 status dependent in all cell lines. (Abstract truncated at 2000 characters) | |
Deskriptorji | TUMOR CELLS, CULTURED SARCOMA, EXPERIMENTAL ELECTROPORATION DRUG DELIVERY SYSTEMS GENE THERAPY MICE CISPLATIN GENES, P53 |