1. Electrochemotherapy with bleomycin is effective in BRAF mutated melanoma cells and interacts with BRAF inhibitorsTanja Jesenko, Lara Prosen, Maja Čemažar, Tjaša Potočnik, Gregor Serša, 2016, izvirni znanstveni članek Povzetek: The aim of the study was to explore the effectiveness of electrochemotherapy (ECT) during the treatment of melanoma patients with BRAF inhibitors. Its effectiveness was tested on BRAF mutated and non-mutated melanoma cells in vitro and in combination with BRAF inhibitors. Materials and methods. ECT with bleomycin was performed on two human melanoma cell lines, with (SK-MEL-28) or without (CHL-1) BRAF V600E mutation. Cell survival was determined using clonogenic assay to determine the effectiveness of ECT in melanoma cells of different mutation status. Furthermore, the effectiveness of ECT in concomitant treatment with BRAF inhibitor vemurafenib was also determined in BRAF mutated cells SK-MEL-28 with clonogenic assay. Results. The survival of BRAF V600E mutated melanoma cells was even lower than non-mutated cells, indicating that ECT is effective regardless of the mutational status of melanoma cells. Furthermore, the synergistic interaction between vemurafenib and ECT with bleomycin was demonstrated in the BRAF V600E mutated melanoma cells. Conclusions. The effectiveness of ECT in BRAF mutated melanoma cells as well as potentiation of its effectiveness during the treatment with vemurafenib in vitro implies on clinical applicability of ECT in melanoma patients with BRAF mutation and/or during the treatment with BRAF inhibitors.
Ključne besede: electrochemotherapy, BRAF inhibitors, vemurafenib, melanoma
Objavljeno v DiRROS: 30.04.2024; Ogledov: 28; Prenosov: 4
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2. Safety and efficacy of IL-12 plasmid DNA transfection into pig skin : supportive data for human clinical trials on gene therapy and vaccinationUrša Lampreht Tratar, Tanja Jesenko, Maša Omerzel, Alenka Seliškar, Urban Stupan, Mihajlo Djokić, Jerneja Sredenšek, Blaž Trotovšek, Gregor Serša, Maja Čemažar, 2024, izvirni znanstveni članek Povzetek: Gene electrotransfer (GET) of plasmids encoding interleukin 12 (IL-12) has already been used for the treatment of various types of tumors in human oncology and as an adjuvant in DNA vaccines. In recent years, we have developed a plasmid encoding human IL-12 (phIL12) that is currently in a phase I clinical study. The aim was to confirm the results of a non-clinical study in mice on pharmacokinetic characteristics and safety in a porcine model that better resembled human skin. The GET of phIL12 in the skin was performed on nine pigs using different concentrations of plasmid phIL12 and invasive (needle) or noninvasive (plate) types of electrodes. The results of our study demonstrate that the GET of phIL-12 with needle electrodes induced the highest expression of IL-12 at the protein level on day 7 after the procedure. The plasmid was distributed to all tested organs; however, its amount decreased over time and was at a minimum 28 days after GET. Based on plasmid copy number and expression results, together with blood analysis, we showed that IL-12 GET is safe in a porcine animal model. Furthermore, we demonstrated that pigs are a valuable model for human gene therapy safety studies.
Ključne besede: interleukin 12, gene electrotransfer, immunotherapy
Objavljeno v DiRROS: 18.04.2024; Ogledov: 53; Prenosov: 29
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3. Effects of electrochemotherapy on immunologically important modifications in tumor cellsUrša Kešar, Boštjan Markelc, Tanja Jesenko, Katja Uršič Valentinuzzi, Maja Čemažar, Primož Strojan, Gregor Serša, 2023, izvirni znanstveni članek Povzetek: Electrochemotherapy (ECT) is a clinically acknowledged method that combines the use of anticancer drugs and electrical pulses. Electrochemotherapy with bleomycin (BLM) can induce immunogenic cell death (ICD) in certain settings. However, whether this is ubiquitous over different cancer types and for other clinically relevant chemotherapeutics used with electrochemotherapy is unknown. Here, we evaluated in vitro in the B16-F10, 4T1 and CT26 murine tumor cell lines, the electrochemotherapy triggered changes in the ICD-associated damage-associated molecular patterns (DAMPs): Calreticulin (CRT), ATP, High Mobility Group Box 1 (HMGB1), and four immunologically important cellular markers: MHCI, MHC II, PD-L1 and CD40. The changes in these markers were investigated in time up to 48 h after ECT. We showed that electrochemotherapy with all three tested chemotherapeutics induced ICD-associated DAMPs, but the induced DAMP signature was cell line and chemotherapeutic concentration specific. Similarly, electrochemotherapy with CDDP, OXA or BLM modified the expression of MHC I, MHC II, PD-L1 and CD40. The potential of electrochemotherapy to change their expression was also cell line and chemotherapeutic concentration specific. Our results thus put the electrochemotherapy with clinically relevant chemotherapeutics CDDP, OXA and BLM on the map of ICD inducing therapies.
Ključne besede: electrochemotherapy, cisplatin, immune response
Objavljeno v DiRROS: 21.03.2024; Ogledov: 91; Prenosov: 50
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4. 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, izvirni znanstveni članek Objavljeno v DiRROS: 21.03.2024; Ogledov: 107; Prenosov: 33
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5. 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, objavljeni povzetek znanstvenega prispevka na konferenci Ključne besede: miši, rak glave in vratu, gensko zdravljenje
Objavljeno v DiRROS: 19.06.2023; Ogledov: 363; Prenosov: 159
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7. 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, objavljeni povzetek znanstvenega prispevka na konferenci Ključne besede: solidni tumorji, elektroprenos genov, radioterapija
Objavljeno v DiRROS: 19.06.2023; Ogledov: 369; Prenosov: 172
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8. Sproščanje dejavnikov imunogene celične smrti HMGB1 in ATP iz celičnih linij se povečuje s časom po obsevanjuUrša Kešar, Tanja Jesenko, Boštjan Markelc, Katja Uršič Valentinuzzi, Maja Čemažar, Primož Strojan, Gregor Serša, 2023, objavljeni povzetek znanstvenega prispevka na konferenci Ključne besede: miši, obsevanje, radioterapija
Objavljeno v DiRROS: 19.06.2023; Ogledov: 305; Prenosov: 145
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9. Nižje število cirkulirajočih tumorskih celic v poznih linijah razsejanega raka dojkSilvester Jernej, Klara Geršak, Marina Mencinger, Tanja Ovčariček, Tanja Jesenko, Živa Modic, Simona Miceska, Maja Čemažar, Veronika Kloboves-Prevodnik, Cvetka Grašič-Kuhar, 2022, objavljeni povzetek strokovnega prispevka na konferenci Ključne besede: onkologija, rak dojke, kemoterapija
Objavljeno v DiRROS: 03.02.2023; Ogledov: 434; Prenosov: 123
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10. Morfološke značilnosti cirkulirajočih tumorskih celic raka dojk v krvi po izolaciji na podlagi njihovih fizikalnih ali bioloških lastnostiSimona Miceska, Tanja Jesenko, Živa Modic, Cvetka Grašič-Kuhar, Maja Čemažar, Urška Matkovič, Jerneja Varl, Anamarija Kuhar, Veronika Kloboves-Prevodnik, 2022, objavljeni povzetek znanstvenega prispevka na konferenci Ključne besede: citologija, diagnostika, onkologija
Objavljeno v DiRROS: 27.01.2023; Ogledov: 422; Prenosov: 121
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