1. Adjuvant TNF-a therapy to electrochemotherapy with intravenous cisplatin in murine sarcoma exerts synergistic antitumor effectivenessMaja Čemažar, Vesna Todorović, Janez Ščančar, Urša Lampreht Tratar, Monika Savarin, Urška Kamenšek, Simona Kranjc Brezar, Andrej Cör, Gregor Serša, 2015, original scientific article Abstract: Background. Electrochemotherapy is a tumour ablation modality, based on electroporation of the cell membrane, allowing non-permeant anticancer drugs to enter the cell, thus augmenting their cytotoxicity by orders of magnitude. In preclinical studies, bleomycin and cisplatin proved to be the most suitable for clinical use. Intravenous administration of cisplatin for electrochemotherapy is still not widely accepted in the clinics, presumably due to its lower antitumor effectiveness, but adjuvant therapy by immunomodulatory or vascular-targeting agents could provide a way for its potentiation. Hence, the aim of the present study was to explore the possibility of adjuvant tumour necrosis factor % (TNF-%) therapy to potentiate antitumor effectiveness of electrochemotherapy with intravenous cisplatin administration in murine sarcoma. Materials and methods. In vivo study was designed to evaluate the effect of TNF-% applied before or after the electrochemotherapy and to evaluate the effect of adjuvant TNF-% on electrochemotherapy with different cisplatin doses. Results. A synergistic interaction between TNF-% and electrochemotherapy was observed. Administration of TNF-% before the electrochemotherapy resulted in longer tumour growth delay and increased tumour curability, and was significantly more effective than TNF-% administration after the electrochemotherapy. Tumour analysis revealed increased platinum content in tumours, TNF-% induced blood vessel damage and increased tumour necrosis after combination of TNF-% and electrochemotherapy, indicating an anti-vascular action of TNF-%. In addition, immunomodulatory effect might have contributed to curability rate of the tumours. Conclusion. Adjuvant intratumoural TNF-% therapy synergistically contributes to electrochemotherapy with intravenous cisplatin administration. Due to its potentiation at all doses of cisplatin, the combined treatment is predicted to be effective also in tumours, where the drug concentration is suboptimal or in bigger tumours, where electrochemotherapy with intravenous cisplatin is not expected to be sufficiently effective.
Keywords: electrochemotherapy, TNF, adjuvant immunotherapy, cisplatin
Published in DiRROS: 17.04.2024; Views: 48; Downloads: 7
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2. Gene immunotherapy of colon carcinoma with IL-2 and IL-12 using gene electrotransferTilen Komel, Maša Omerzel, Urška Kamenšek, Katarina Žnidar, Urša Lampreht Tratar, Simona Kranjc Brezar, Klemen Dolinar, Sergej Pirkmajer, Gregor Serša, Maja Čemažar, 2023, original scientific article Abstract: Gene immunotherapy has become an important approach in the treatment of cancer. One example is the introduction of genes encoding immunostimulatory cytokines, such as interleukin 2 and interleukin 12, which stimulate immune cells in tumours. The aim of our study was to determine the effects of gene electrotransfer of plasmids encoding interleukin 2 and interleukin 12 individually and in combination in the CT26 murine colon carcinoma cell line in mice. In the in vitro experiment, the pulse protocol that resulted in the highest expression of IL-2 and IL-12 mRNA and proteins was used for the in vivo part. In vivo, tumour growth delay and also complete response were observed in the group treated with the plasmid combination. Compared to the control group, the highest levels of various immunostimulatory cytokines and increased immune infiltration were observed in the combination group. Long-term anti-tumour immunity was observed in the combination group after tumour re-challenge. In conclusion, our combination therapy efficiently eradicated CT26 colon carcinoma in mice and also generated strong anti-tumour immune memory.
Keywords: colon carcinoma, gene electrotransfer, gene immunotherapy
Published in DiRROS: 21.03.2024; Views: 95; Downloads: 47
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3. Potentiation of electrochemotherapy by intramuscular IL-12 gene electrotransfer in murine sarcoma and carcinoma with different immunogenicityAleš Sedlar, Tanja Jesenko, Boštjan Markelc, Lara Prosen, Simona Kranjc Brezar, Maša Omerzel, Tanja Blagus, Maja Čemažar, Gregor Serša, 2012, original scientific article Published in DiRROS: 21.03.2024; Views: 73; Downloads: 28
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4. Study of radiation induced changes of phosphorus metabolism in mice by ▫$^{31}P$▫ NMR spectroscopyIgor Serša, Simona Kranjc Brezar, Gregor Serša, Alenka Nemec Svete, Bojan Ložar, Ana Sepe, Jernej Vidmar, Marjeta Šentjurc, 2010, original scientific article Published in DiRROS: 15.03.2024; Views: 88; Downloads: 31
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5. Effect of electroporation on radiosensitization with cisplatin in two cell lines with different chemo- and radiosensitivitySimona Kranjc Brezar, Maja Čemažar, Alenka Grošel, Živa Pipan Tkalec, Gregor Serša, 2003, original scientific article Abstract: Aim. Radiosensitization with cisplatin can be enhanced by electroporation of cells and tumours. The aim of this study was to extend our previous studies ontwo carcinoma tumour models with different chemo-and radiosensitivity in order to evaluate whether this treatment is effective also on less chemo-and radiosensitive tumour cells. Materials and methods. This in vitro study was performed on carcinoma SCK and EAT-E cells. The cytotoxicity of three-modalitytreatment consisting of cisplatin, electroporation and irradiation was determined by the clonogenic assay. Results. The radiosensitizing effect of cisplatin on the two cell lines was greatly enhanced by electroporation. By this combined treatment, less chemo and radiosensitive EAT-E cells were rendered as sensitive as more chemo and radiosensitive SCK cells. Conclusion. The enhancement of cisplatin-induced radiosensitization of cells by electroporation could be beneficially used in the treatment of intrinsically less chemo- and radiosensitive tumours.
Published in DiRROS: 06.02.2024; Views: 131; Downloads: 27
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6. Cryosurgery combined with radiotherapy of tumors in miceAlbert-Peter Fras, Simona Kranjc Brezar, Maja Čemažar, Gregor Serša, 1999, original scientific article Abstract: Tlle aim of this study zuas to determine antitumor effectiveness of cryosurgery alone and in comhination with radiotherapy. Cryosurgery of subcutaneous fibrosarcoma SA-1 tumors in A/J mice was moderately effective trcatmcnt. Tumor growth delay was 10.3 * 3.8 days after 5 minute treatment with nitrogen filled cryo-prohe. Shorter treatment times induced less, but dose dependent antitumor effect. In combined treat- ment, tumors were either first treated by cryosurgery for 3 minutes and then locally irradiated with 10Gy for 5 minutes, or irradiated first and thereafter treated by cryosurgery.The antitumor effectiveness of com- bined treatrnent was sequence dependent; the irradiation of tumors before cryosurgery resulted in better antitumor effect than the irradiation after cryosurgery. These results indicate that radiosensitization may not be always expected, in spite of some reports demonstrating that cryosurgery may have radiosensitizing effect in vivo, and that some other mechanisms may be involved contributing to radiationdamage when cryosurgery follows irradiation.
Published in DiRROS: 22.01.2024; Views: 149; Downloads: 40
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7. Elektrokemoterapija pri lokalnem zdravljenju napredovalega melanomaGregor Serša, Zvonimir Rudolf, Marija Snežna Paulin-Košir, Janja Ocvirk, Maja Čemažar, Simona Kranjc Brezar, Breda Slekovec Kolar, Marko Snoj, 2007, published scientific conference contribution Published in DiRROS: 06.12.2023; Views: 188; Downloads: 54
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8. Razvoj in karakterizacija mišjega modela za študije HPV-pozitivnega raka glave in vratuŽiva Modic, Maja Čemažar, Boštjan Markelc, Andrej Cör, Gregor Serša, Simona Kranjc Brezar, Tanja Jesenko, 2023, published scientific conference contribution abstract Keywords: miši, rak glave in vratu, gensko zdravljenje
Published in DiRROS: 19.06.2023; Views: 356; Downloads: 155
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9. Kombinirano zdravljenje solidnih tumorjev z intratumoralnim genskim elektroprenosom plazmidne DNA z zapisom za protitelesa anti-CTLA4 in obsevanjemSimona Kranjc Brezar, Boštjan Markelc, Tanja Jesenko, Tim Božič, Paul Declerck, Liesl Jacobs, Maja Čemažar, Kevin Hollevoet, Gregor Serša, 2023, published scientific conference contribution abstract Keywords: solidni tumorji, elektroprenos genov, radioterapija
Published in DiRROS: 19.06.2023; Views: 362; Downloads: 167
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