1. Bleomycin electrosclerotherapy (BEST) : mechanistic parallels to electrochemotherapy, experimental models, and unresolved questionsBarbara Lisec, Maja Čemažar, Tobian Muir, Maša Omerzel, Tanja Jesenko, Boštjan Markelc, Aleš Grošelj, Rok Dežman, Miha Štabuc, Dimitrij Kuhelj, Gregor Serša, 2026, review article Keywords: vascular malformations, bleomycin electrosclerotherapy, BEST, electrochemotherapy
Published in DiRROS: 01.04.2026; Views: 147; Downloads: 66
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2. Učinek kombinacije elektrokemoterapije in anti-pd-1 imunoterapije pri mišjih modelih tumorjev z različnim imunskim statusomSimona Kranjc Brezar, Maša Omerzel, Urša Lampreht Tratar, Tanja Jesenko, Barbara Lisec, Gregor Serša, Maja Čemažar, 2025, published scientific conference contribution abstract Keywords: eksperimentalna onkologija, imunoterapija, elektrokemoterapija
Published in DiRROS: 18.03.2026; Views: 236; Downloads: 98
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4. New mitochondrial ▫$K_V$▫1.3 conjugates are potent and specific inducers of apoptosis in cancer modelsŠpela Gubič, Marzia Fois, Ivan Džajić, Katja Kološa, Alja Štern, Maša Omerzel, Tim Božič, Boštjan Markelc, Tanja Jesenko, Maja Čemažar, Bojana Žegura, Tina Kosjek, Andrej Emanuel Cotman, Tihomir Tomašič, Lucija Peterlin-Mašič, 2026, original scientific article Keywords: mitochondrial targeting, mitochondrial KV1.3, apoptosis, cancer
Published in DiRROS: 12.02.2026; Views: 464; Downloads: 160
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5. Between defence and delivery : the DNA sensing response to gene electrotransferTanja Jesenko, Maša Omerzel, Loree C. Heller, Maja Čemažar, 2025, review article Abstract: Gene therapy has emerged as a transformative biomedical approach, offering new therapeutic possibilities from many so far uncurable diseases through the introduction of recombinant nucleic acids into target cells. Among non-viral delivery techniques, gene electrotransfer (GET) has become one of the frequently applied methods in clinical trials. It is based on the application of short, high-intensity electric pulses that transiently permeabilize cell membranes and enable the efficient transfer of plasmid DNA or other types of recombinant nucleic acids into various cell types. Beyond its role in gene delivery, GET can trigger complex cellular responses, as the introduced DNA interacts with intracellular DNA sensing pathways involved in innate immunity and inflammation. These responses can influence the therapeutic outcome – either by enhancing antitumour and vaccine-related immune activation or by reducing transfection efficiency when excessive inflammation or cell death occur. Our experimental findings in tumour, muscle, and skin models have shown that even non-coding plasmid DNA delivered by GET can induce local immune stimulation and tissue-specific inflammatory signaling, suggesting that the delivered DNA itself contributes to therapeutic efficacy. Conclusions The dual nature of cellular responses following plasmid DNA GET represents both an opportunity and a challenge. Controlled activation of innate immunity can be harnessed to amplify antitumour or vaccine efficacy, while excessive responses may hinder applications requiring cell survival and sustained expression. Understanding these mechanisms enables the rational optimization of GET parameters and plasmid vector design to fully exploit the adjuvant effect or reduce the off-target effect of DNA sensing after GET, based on the desired application.
Keywords: gene electrotransfer, DNA sensors, gene therapy
Published in DiRROS: 16.01.2026; Views: 288; Downloads: 107
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6. The role of focal adhesion kinase in bladder cancer : translation from in vitro to ex vivo human urothelial carcinomasGaja Markovič, Nataša Resnik, Aleksandar Janev, Daša Zupančič, Gašper Grubelnik, Maruša Debeljak, Maja Čemažar, Tanja Jesenko, Maša Omerzel, Tomaž Smrkolj, Mateja Erdani-Kreft, 2025, original scientific article Abstract: Background: Focal adhesion kinase (FAK), a cytoplasmic tyrosine kinase, plays a crucial role in focal adhesion turnover by interfacing between the extracellular space, transmembrane integrins, and actin filaments. Its significance for the progression of several malignancies, including bladder cancer, has been well-documented. However, its precise role and the implications of its inhibition in bladder cancer tissues and urothelial in vitro models has not been fully explored. This study examined FAK expression and function in human bladder cancer biopsies and in vitro bladder cancer models. Materials and methods: Ex vivo analyses were performed using reverse transcription-quantitative PCR (qRT-PCR), western blotting, and immunohistochemistry to compare FAK expression between bladder cancer tissues and adjacent normal tissues. In vitro, FAK expression was assessed in low-grade (LG) human non-invasive papilloma urothelial cell line RT4 for NMIBC (Ta), high-grade (HG) human muscle-invasive cancer urothelial cell line T24 for MIBC (T2) and normal porcine urothelial (NPU) cells using qRT-PCR and western blotting, as well as flow cytometry for the quantification of FAK-positive RT4 and T24 cells. The role of FAK in cancer cell survival was explored in vitro using microRNA (miRNA) to silence FAK expression. Additionally, we used FAK inhibitors PND-1186, PF-573228 and defactinib to investigate the effects of FAK inhibition on normal compared to cancerous bladder urothelial cells. Results: Ex vivo analyses demonstrated significantly higher FAK expression in bladder cancer tissues compared to adjacent normal tissues. Similarly, in vitro analyses showed significantly higher FAK expression in RT4 and T24 cells than NPU cells. Silencing FAK using anti-FAK plasmids led to increased caspase-3-mediated apoptosis of RT4 and T24 cells and growth reduction of stably transfected T24 cells. Importantly, based on cell viability assays, treatment with 100 μM defactinib for 2 hours per day on 3 consecutive days was identified as a clinically relevant regimen. Under this treatment, the viability of differentiated NPU cells remained high at 108.4 ± 17.1%, while the viability of 2-day RT4 and 2-day T24 cells was drastically reduced to 4.1 ± 2.7% and 7.6 ± 2.9%, respectively. Conclusions: To our knowledge, this is the first report demonstrating the role of FAK and its inhibition across both normal and cancerous bladder urothelial models. This study highlights the critical role of FAK in the progression of human bladder cancer and establishes a foundation for exploring FAK inhibition as a potential therapeutic approach in bladder cancer treatment.
Keywords: bladder cancer, defactinib, focal adhesion kinase, human urothelial carcinoma, urothelial cell
Published in DiRROS: 09.12.2025; Views: 333; Downloads: 194
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7. Expression of inducible damage-associated molecular patterns after interleukin-12 gene electrotransfer in mouse melanoma and colorectal cell linesAjda Medved, Maša Omerzel, Tanja Jesenko, Simon Buček, Gregor Serša, Maja Čemažar, 2025, original scientific article Abstract: Interleukin-12 (IL-12) has demonstrated potent antitumor effects by activating natural killer (NK) and T cells, but its systemic administration poses challenges due to toxicity. This study investigated gene electrotransfer (GET) as a localized delivery method for IL-12 plasmids in B16F10 and CT26 tumor cells and its effect on the expression of damage-associated molecular patterns (DAMPs) and several cytokines. We observed the activation of cytosolic sensors and cytokine production, with the expression of IL-6 and TNF-α upregulated only after IL-12 GET, suggesting the involvement of inducible damage-associated molecular patterns (iDAMPs) in the immune response to IL-12 gene therapy. These findings highlight the multifaceted immune activation triggered by GET, offering insights for improving IL-12-based cancer therapies.
Keywords: gene electrotransfer, cytokine, interleukin-12
Published in DiRROS: 05.12.2025; Views: 953; Downloads: 156
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8. In vitro evaluation of electrochemotherapy combined with sotorasib in pancreatic carcinoma cell lines harboring distinct kras mutationsTanja Jesenko, Maša Omerzel, Tina Živič, Gregor Serša, Maja Čemažar, 2025, original scientific article Abstract: Pancreatic cancer is among the deadliest malignancies, with limited treatment options and poor prognosis. Novel strategies are therefore urgently needed. Sotorasib, a KRAS G12C-specific inhibitor, offers targeted treatment for a small subset of patients with this mutation. Electrochemotherapy (ECT), which enhances the cytotoxicity of chemotherapeutic agents through electroporation-induced membrane permeabilization, has shown promise in various tumor types, including deep-seated malignancies such as pancreatic cancer. Combining ECT with sotorasib may potentiate antitumor effects in KRAS G12C-mutated pancreatic cancer; however, preclinical data on such combinations are lacking. This proof-of-concept study evaluated the cytotoxic effects of ECT using bleomycin (BLM) or cisplatin (CDDP) in combination with sotorasib in KRAS G12C-mutated MIA PaCa-2 and KRAS G12D-mutated PANC-1 pancreatic cancer cell lines. ECT alone significantly reduced cell viability, particularly in MIA PaCa-2 cells, where electric pulses induced approximately 75% cell death. Combining ECT with sotorasib resulted in an additive effect on KRAS G12C-mutated MIA PaCa-2 cells, though no synergy was observed, likely due to the high intrinsic sensitivity to electric pulses. These results support the potential of combining physical and molecular therapies in a subset of pancreatic cancer patients and lay the groundwork for further in vivo studies to optimize treatment parameters and explore clinical translatability.
Keywords: bleomycin, cisplatin, electrochemotherapy, pancreatic cancer
Published in DiRROS: 26.11.2025; Views: 555; Downloads: 168
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9. Long-term outcomes of reduced-dose bleomycin in electrochemotherapy for basal cell carcinoma in elderly patientsAleš Grošelj, Črt Jamšek, Simona Kranjc Brezar, Maja Čemažar, Maša Omerzel, Luka Pušnik, Gregor Serša, 2025, original scientific article Abstract: Electrochemotherapy (ECT) is a minimally invasive treatment option for basal cell carcinoma (BCC), which is particularly advantageous in the elderly population. This study evaluated the long-term effects of treating BCC in older patients using ECT with a reduced dose of bleomycin (10,000 IU/m2) and compared the results to patients who received the standard dose of bleomycin (15,000 IU/m2). The retrospective analysis included 116 patients aged over 65 years with 257 histologically confirmed BCCs. Tumors were treated with either the standard dose (n = 82) or the reduced dose (n = 175) of bleomycin. The results showed that the recurrence rate was comparable between the groups, particularly in the first year after treatment. The reduced-dose group exhibited a greater recurrence rate after the first year, which may be attributed to a weaker local immune response due to the de-escalated dose of bleomycin. Nonetheless, administering a standard bleomycin dosage as a salvage treatment in the event of recurrence proved highly effective. These findings suggest that ECT with a reduced bleomycin dose is a viable option for treating BCC in elderly patients, particularly those with shorter life expectancy.
Keywords: bleomycin, electrochemotherapy, head and neck, nonmelanoma skin cancer
Published in DiRROS: 25.11.2025; Views: 620; Downloads: 237
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10. Bleomycin electrosclerotherapy (BEST) for the treatment of vascular malformations : an International Network for Sharing Practices on Electrochemotherapy (InspECT) study group reportTobian Muir, Giulia Bertino, Aleš Grošelj, Lakshmi Ratnam, Erika Kis, Joy Odili, Ian McCafferty, Walter A Wohlgemuth, Maja Čemažar, Aljoša Krt, Maša Omerzel, Alessandro Zanasi, Michela Battista, Francesca De Terlizzi, Luca Giovanni Campana, Gregor Serša, 2023, review article Abstract: Biomedical applications of electroporation are expanding out of the field of oncology into vaccination, treatment of arrhythmias and now in the treatment of vascular malformations. Bleomycin is a widely used sclerosing agent in the treatment of various vascular malformations. The application of electric pulses in addition to bleomycin enhances the effectiveness of the drug, as demonstrated by electrochemotherapy, which utilizes bleomycin in the treatment of tumors. The same principle is used in bleomycin electrosclerotherapy (BEST). The approach seems to be effective in the treatment of low-flow (venous and lymphatic) and, potentially, even high-flow (arteriovenous) malformations. Although there are only a few published reports to date, the surgical community is interested, and an increasing number of centers are applying BEST in the treatment of vascular malformations. Within the International Network for Sharing Practices on Electrochemotherapy (InspECT) consortium, a dedicated working group has been constituted to develop standard operating procedures for BEST and foster clinical trials. By treatment standardization and successful completion of clinical trials demonstrating the effectiveness and safety of the approach, higher quality data and better clinical outcomes may be achieved.
Keywords: vascular malformations, electrosclerotherapy, bleomycin
Published in DiRROS: 25.07.2024; Views: 1373; Downloads: 431
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