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1.
Effect of bleomycin hydrolase expression in tumor tissue on the therapeutic effectiveness of electrochemotherapy
Jan Bogataj, Urša Lampreht Tratar, Gregor Serša, Maja Čemažar, Aleš Grošelj, Maša Omerzel, 2025, original scientific article

Abstract: 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.
Keywords: electrochemotherapy, bleomycin hydrolase, predictive biomarker, murine models
Published in DiRROS: 20.04.2026; Views: 140; Downloads: 103
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Quality of life of women with recurrent vulvar cancer treated with electrochemotherapy
Gregor Vivod, Ines Cilenšek, Nina Kovačević, Gregor Serša, Maja Čemažar, Sebastjan Merlo, 2025, original scientific article

Abstract: Background: The quality of life of patients undergoing oncologic treatment has become an important issue in recent years. Owing to potential mutilation following surgery for vulvar cancer, more conservative approaches have evolved with the integration of new local ablative therapies, such as electrochemotherapy. The aim of this study was to determine the quality of life of women with vulvar cancer recurrence treated with electrochemotherapy for nonpalliative purposes. Patients and methods: Eleven patients with vulvar cancer recurrence were treated with electrochemotherapy from July 2020 to December 2023. Patients completed different questionnaires: the EuroQol - 5 Dimension (EQ-5D), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Vulva Cancer 34 (EORTC QLQ-VU34) and visual analog pain scale (VAS) before and one, three and six months after electrochemotherapy. As a control group, fifteen patients with vulvar cancer recurrence treated with wide local excision completed the EORTC QLQ-C30 and VAS questionnaires before surgery and three and six months after surgery. Results: No significant differences in EQ-5D scores were found between quality of life before electrochemotherapy and at each follow-up visit. A comparison of the EORTC QLQ-C30 scores between the electrochemotherapy and surgery groups showed a significant difference in physical functioning, fatigue, insomnia, and global health status three months after the procedure and in role, cognitive, social functioning and appetite loss six months after the procedure, all of which were in favor of the electrochemotherapy group. The EORTC QLQ-VU34 questionnaire showed improvements in urinary symptoms and symptoms related to scarring and mutilation of the external genitalia in the electrochemotherapy group. The VAS score did not differ significantly between the electrochemotherapy and surgical groups. Conclusions: The study showed that the quality of life after treatment with electrochemotherapy is better in some segments than after surgical treatment.
Keywords: bleomycin, electrochemotherapy, quality of life
Published in DiRROS: 16.01.2026; Views: 317; Downloads: 126
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Electrochemotherapy (ECT) in treatment of mucosal head and neck tumors : an international network for sharing practices on ECT (InspECT) study group report
Giulia Bertino, Marta Minuti, Aleš Grošelj, Črt Jamšek, Barbara Silvestri, Silvia Carpene, Paolo Matteucci, Giuseppe Riva, Giancarlo Pecorari, Matteo Mascherini, Gregor Serša, 2024, original scientific article

Abstract: The aim of this multicenter study was to evaluate the effectiveness and safety of electrochemotherapy (ECT) for the treatment of mucosal tumors in the head and neck. A total of 71 patients with 84 nodules of different histologies in the oral cavity, pharynx and larynx treated by ECT were evaluated. The data were collected from the InspECT database from 10 participating centers throughout Europe. Primary and recurrent/secondary tumors of different histologies were treated. The overall response rate was 65 %, with a 33 % complete response rate with limited side effects. The response rates of the primary and secondary tumors were not different. However, smaller tumors responded better than tumors larger than 3 cm in diameter. Furthermore, the tumors that were treated with curative intent responded significantly better than those treated with palliative intent. This study demonstrated the feasibility, safety and effectiveness of ECT in a larger cohort of patients with mucosal lesions in the head and neck region. Based on the available data, ECT can be used for the treatment of recurrent and, in some cases, primary mucosal tumors located in the oral cavity, larynx, and pharynx. A better response was obtained in patients with smaller primary tumors treated with curative intent.
Keywords: electrochemotherapy, mucosal cancer, head cancer, neck cancer, ECT
Published in DiRROS: 05.12.2025; Views: 910; Downloads: 293
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In vitro evaluation of electrochemotherapy combined with sotorasib in pancreatic carcinoma cell lines harboring distinct kras mutations
Tanja 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: 624; Downloads: 219
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Long-term outcomes of reduced-dose bleomycin in electrochemotherapy for basal cell carcinoma in elderly patients
Aleš 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: 687; Downloads: 271
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Electrochemotherapy for basal cell carcinoma in the head and neck region : 5-year follow-up from the Insp-ECT registry
Aleš Grošelj, Giulia Bertino, Marta Minuti, James A. P. Clover, Camilla Kjaer Lonkvist, Erika Kis, Christian Kunte, Tobian Muir, Francesco Russano,, Francesca De Terlizzi, Joy Odili, Gregor Serša, 2025, original scientific article

Abstract: Basal cell carcinoma (BCC) is a cutaneous malignancy that typically appears in sun-exposed areas. We analyzed data from the Insp-ECT registry of all patients affected by BCC in the head and neck region. The aim of this study was to evaluate the safety and efficacy of electrochemotherapy (ECT) on a 5-year basis. Patients and methods A cohort of 132 patients was included. They were treated by ECT according to the current Standard Operating Procedures. The median age was 74 years (range 41–93). There was a median of 1 nodule per patient (range 1–7), and the median size of the lesions was 1.4 cm (range 0.5–5.0 cm). Results Patients tolerated ECT well, and 96% agreed to repeat it if needed. The side effects were mild and temporary. All patients achieved a complete clinical response after 1 to 3 ECT sessions. During the first year of follow-up, 4 (3%) patients experienced recurrence, which was treated (2 with ECT, 1 with surgery, and 1 with a combination of ECT and surgery), after which they remained free of disease until the end of follow-up at 5 years. Five patients reported recurrence thereafter and were treated according to their condition. At the 5-year follow-up, the disease-free survival (DFS) rate was 92% (95% confidence interval [CI]: 87%–96%). At that time, 3 patients were alive with disease (2%), and 124 patients were free of disease (98%). Conclusions This study shows the feasibility and efficacy of ECT treatment in elderly patients with BCC tumors in aesthetically and functionally sensitive areas, with negligible toxicity. Comparable efficacy to other treatment modalities was demonstrated at 1 year and 5 years of follow-up in terms of DFS.
Keywords: basal cell carcinoma, electrochemotherapy, preživetje brez ponovitve bolezni
Published in DiRROS: 25.11.2025; Views: 666; Downloads: 239
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8.
Treatment of vulvar cancer recurrences with electrochemotherapy : a detailed analysis of possible causes for unsuccessful treatment
Gregor Vivod, Tanja Jesenko, Gorana Gašljević, Nina Kovačević, Maša Omerzel, Gregor Serša, Sebastjan Merlo, Maja Čemažar, 2023, original scientific article

Abstract: Background. Electrochemotherapy has good local effectiveness in the treatment of vulvar cancer. Most studies have reported the safety and effectiveness of electrochemotherapy for palliative treatment of gynecological cancers and mostly vulvar squamous cell carcinoma. Some tumors, however, fail to respond to electrochemotherapy. The biological features/determinants for the nonresponsiveness are not determined yet. Patient and methods. A recurrence of vulvar squamous cell carcinoma was treated by electrochemotherapy using intravenous administration of bleomycin. The treatment was performed by hexagonal electrodes according to standard operating procedures. We analyzed the factors that could determine nonresponsiveness to electrochemotherapy. Results. Based on the presented case of nonresponsive vulvar recurrence to electrochemotherapy, we hypothesize that the vasculature of the tumors prior to treatment may predict the response to electrochemotherapy. The histological analysis showed minimal presence of blood vessels in the tumor. Thus, low perfusion may reduce drug delivery and lead to a lower response rate because of the minor antitumor effectiveness of vascular disruption. In this case, no immune response in the tumor was elicited by electrochemotherapy. Conclusions. In this case, of nonresponsive vulvar recurrence treated by electrochemotherapy, we analyzed possible factors that could predict treatment failure. Based on histological analysis, low vascularization of the tumor was observed, which hampered drug delivery and distribution and resulted in no vascular disrupting action of electrochemotherapy. All these factors could contribute to ineffective treatment with electrochemotherapy.
Keywords: electrochemotherapy, bleomycin, vulvar cancer
Published in DiRROS: 25.07.2024; Views: 1287; Downloads: 521
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Sunitinib potentiates the cytotoxic effect of electrochemotherapy in pancreatic carcinoma cells
Maša Omerzel, Tanja Jesenko, Boštjan Markelc, Anja Cerovšek, Gregor Serša, Maja Čemažar, 2022, original scientific article

Abstract: One of the new treatment options for unresectable locally advanced pancreatic cancer is electro-chemotherapy (ECT), a local ablative therapy that potentiates the entry of chemotherapeutic drugs into the cells, by the application of an electric field to the tumor. Its feasibility and safety were demonstrated in preclinical and clinical studies; however, there is a lack of preclinical studies assessing the actions of different drugs used in ECT, their mechanisms and interactions with other target drugs that are used in clinical practice. Materials and methods. The aim of the study was to determine the cytotoxicity of two chemotherapeutic drugs usually used in ECT (bleomycin and cisplatin) in the BxPC-3 human pancreatic carcinoma cell line and evaluate the interactions of ECT with the targeted drug sunitinib. First, the cytotoxicity of ECT using both chemotherapeutics was determined. In the next part, the interactions of ECT and sunitinib were evaluated through determination of combined cytotoxicity, sunitinib targets and kinetics of cell death.Results. The results demonstrate that ECT is effective in pancreatic cancer cell line, especially when bleomycin is used, with the onset of cell death in the first hours after the treatment, reaching a plateau at 20 hours after the treat-ment. Furthermore, we provide the rationale for combining ECT with bleomycin and the targeted drug sunitinib to potentiate cytotoxicity. The combined treatment of sunitinib and ECT was synergistic for bleomycin only at the high-est used concentration of bleomycin 0.14 μM, whereas with lower doses of bleomycin, this effect was not observed. The interaction of ECT and treatment with sunitinib was confirmed by course of the cell death, also indicating on synergism
Keywords: electrochemotherapy, pancreas, sunitinib, pancreatic cancer
Published in DiRROS: 24.07.2024; Views: 1205; Downloads: 733
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