1. Effect of bleomycin hydrolase expression in tumor tissue on the therapeutic effectiveness of electrochemotherapyJan Bogataj, Urša Lampreht Tratar, Gregor Serša, Maja Čemažar, Aleš Grošelj, Maša Omerzel, 2025, izvirni znanstveni članek Povzetek: Electrochemotherapy (ECT) is a cancer treatment that combines application of short electrical pulses with chemotherapy drugs to improve their delivery into tumor cells. Bleomycin is one of the most effective drugs used in ECT, but its success can vary depending on the tumor type. One possible reason is the presence of bleomycin hydrolase (BLMH), an enzyme that inactivates bleomycin. In this study, we measured BLMH levels in different mouse tumor cell lines and tumors grown in animals. Thereafter we compared the levels of BLMH with tumor response to ECT and found a correlation with BLMH content, i.e., tumors with higher BLMH content responded poorly. These findings suggest that levels of BLMH could serve as a predictive marker for ECT effectiveness. Testing for BLMH before treatment may help personalize therapy and identify patients most likely to benefit from ECT.
Ključne besede: electrochemotherapy, bleomycin hydrolase, predictive biomarker, murine models
Objavljeno v DiRROS: 20.04.2026; Ogledov: 140; Prenosov: 103
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2. Phase I trial of phIL12 plasmid intratumoral gene electrotransfer in patients with basal cell carcinoma in head and neck regionPrimož Strojan, Tanja Jesenko, Maša Omerzel, Črt Jamšek, Aleš Grošelj, Urša Lampreht Tratar, Boštjan Markelc, Gorana Gašljević, Alojz Ihan, Franc Smrekar, Matjaž Peterka, Maja Čemažar, Gregor Serša, 2025, izvirni znanstveni članek Ključne besede: phase I clinical trial, phIL12 plasmid, interleukin-12, gene electrotransfer, basal cell carcinoma
Objavljeno v DiRROS: 13.04.2026; Ogledov: 150; Prenosov: 109
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3. 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, pregledni znanstveni članek Ključne besede: vascular malformations, bleomycin electrosclerotherapy, BEST, electrochemotherapy
Objavljeno v DiRROS: 01.04.2026; Ogledov: 232; Prenosov: 127
Celotno besedilo (2,26 MB)
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4. 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, objavljeni povzetek znanstvenega prispevka na konferenci Ključne besede: eksperimentalna onkologija, imunoterapija, elektrokemoterapija
Objavljeno v DiRROS: 18.03.2026; Ogledov: 295; Prenosov: 128
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6. 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, izvirni znanstveni članek Ključne besede: mitochondrial targeting, mitochondrial KV1.3, apoptosis, cancer
Objavljeno v DiRROS: 12.02.2026; Ogledov: 544; Prenosov: 222
Celotno besedilo (7,40 MB)
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7. Between defence and delivery : the DNA sensing response to gene electrotransferTanja Jesenko, Maša Omerzel, Loree C. Heller, Maja Čemažar, 2025, pregledni znanstveni članek Povzetek: 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.
Ključne besede: gene electrotransfer, DNA sensors, gene therapy
Objavljeno v DiRROS: 16.01.2026; Ogledov: 385; Prenosov: 137
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8. 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, izvirni znanstveni članek Povzetek: 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.
Ključne besede: bladder cancer, defactinib, focal adhesion kinase, human urothelial carcinoma, urothelial cell
Objavljeno v DiRROS: 09.12.2025; Ogledov: 378; Prenosov: 248
Celotno besedilo (2,15 MB)
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9. 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, izvirni znanstveni članek Povzetek: 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.
Ključne besede: gene electrotransfer, cytokine, interleukin-12
Objavljeno v DiRROS: 05.12.2025; Ogledov: 1032; Prenosov: 183
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10. 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, izvirni znanstveni članek Povzetek: 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.
Ključne besede: bleomycin, cisplatin, electrochemotherapy, pancreatic cancer
Objavljeno v DiRROS: 26.11.2025; Ogledov: 624; Prenosov: 219
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