1. 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: 155; Downloads: 49
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2. Treatment of vulvar cancer recurrences with electrochemotherapy : a detailed analysis of possible causes for unsuccessful treatmentGregor 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: 130; Downloads: 102
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3. Long term response of electrochemotherapy with reduced dose of bleomycin in elderly patients with head and neck non-melanoma skin cancerČrt Jamšek, Gregor Serša, Maša Omerzel, Aleš Grošelj, 2020, original scientific article Abstract: . Electrochemotherapy (ECT) is a local cancer treatment based on electroporation where the electric field is used to enhance cell membrane permeability and thereby facilitating the transition of chemotherapeutic agents into the cell. For the treatment of non-melanoma skin cancer, a standard dosage of 15,000 IU/m2 bleomycin (BLM) is used. The aim of the present study was to evaluate the long-term ECT response in the group of elderly patients with non-melanoma skin cancer treated with a reduced dose of BLM in comparison to the outcome in the patients treated with the standard dose of BLM. Patients and methods. Twenty-eight patients older than 65 years, with a total of 52 non-melanoma skin lesions were included in the study. Twelve patients (24 lesions) in the experimental group received a reduced dose of BLM (10,000 IU/m2), 16 patients (28 lesions) were treated with a standard dose of BLM (15,000 IU/m2). Results. No statistically significant difference in tumor control was observed between both groups. In the experimental group, tumors recurred in 39.0% of treated lesions in a median follow-up time of 28 months. In the control group, the recurrence rate of treated lesions was 15.4% in a median follow-up time of 40 months. Conclusions. ECT with a reduced dose of BLM is a feasible treatment option for elderly patients with equal efficacy to standard dose treatment and should be considered as a treatment modality in advanced aged patients with comorbidities, where overall life expectancy is poor Keywords: electrochemotherapy, bleomycin, non-melanoma skin cancer Published in DiRROS: 12.07.2024; Views: 146; Downloads: 43
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4. Electrochemotherapy with bleomycin : The first clinical experience in malignant melanoma patientsZvonimir Rudolf, Borut Štabuc, Maja Čemažar, Damijan Miklavčič, Lojze Vodovnik, Gregor Serša, 1995, original scientific article Keywords: melanoma therapy, bleomycin, electric stimulation therapy Published in DiRROS: 15.01.2024; Views: 387; Downloads: 83
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5. Elektrokemoterapija malignega melanomaGregor Serša, Borut Štabuc, Tanja Čufer, Boris Jančar, Damijan Miklavčič, Maja Čemažar, Zvonimir Rudolf, 1999, published scientific conference contribution Keywords: melanom, zdravljenje, bleomicin, cisplatin, električna stimulacija, elektrokemoterapija, elektroporacija, melanoma therapy, bleomycin, cisplatin, electric stimulation therapy, electrochemotherapy, electroporation Published in DiRROS: 27.11.2023; Views: 425; Downloads: 126
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6. Bleomycin concentration in patientsʹ plasma and tumors after electrochemotherapy : a study from InspECT GroupAleš Grošelj, Maša Omerzel, Mojca Kržan, Tina Kosjek, Krisztina Bottyán, Helena Plešnik, Črt Jamšek, Maja Čemažar, Erika Kis, Gregor Serša, 2021, original scientific article Keywords: electrochemotherapy, electroporation, bleomycin Published in DiRROS: 10.10.2022; Views: 700; Downloads: 341
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7. Biological factors of the tumour response to electrochemotherapy : review of the evidence and a research roadmapGregor Serša, Katja Uršič Valentinuzzi, Maja Čemažar, Richard Heller, Maša Omerzel, Luca Giovanni Campana, 2021, review article Abstract: The beneficial effects of electrochemotherapy (ECT) for superficial tumours and, more recently, deepseated malignancies in terms of local control and quality of life are widely accepted. However, the variability in responses across histotypes needs to be explored. Currently, patient selection for ECT is based on clinical factors (tumour size, histotype, and exposure to previous oncological treatments), whereas there are no biomarkers to predict the response to treatment. In this field, two major areas of investigation can be identified, i.e., tumour cell characteristics and the tumour microenvironment (vasculature, extracellular matrix, and immune infiltrate). For each of these areas, we describe the current knowledge and discuss how to foster further investigation. This review aims to provide a summary of the currently used guiding clinical factors and delineates a research roadmap for future studies to identify putative biomarkers of response to ECT. These biomarkers may allow researchers to improve ECT practice by customising treatment parameters, manipulating the tumour and its microenvironment, and exploring novel therapeutic combinations. Keywords: biological factors, biomarkers, electrochemotherapy, bleomycin, cisplatin Published in DiRROS: 23.09.2022; Views: 707; Downloads: 227
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8. PARP inhibitor olaparib has a potential to increase the effectiveness of electrochemotherapy in BRCA1 mutated breast cancer in miceMaša Omerzel, Tanja Jesenko, Boštjan Markelc, Larisa Janžič, Maja Čemažar, Gregor Serša, 2021, original scientific article Abstract: Electrochemotherapy (ECT), a local therapy, has different effectiveness among tumor types. In breast can-cer, its effectiveness is low; therefore, combined therapies are needed. The aim of our study was to com-bine ECT with PARP inhibitor olaparib, which could inhibit the repair of bleomycin or cisplatin inducedDNA damage and potentiate the effectiveness of ECT. The effects of combined therapy were studied inBRCA1mutated (HCC1937) and non-mutated (HCC1143) triple negative breast cancer cell lines.Therapeutic effectiveness was studied in 2D and 3D cell cultures andin vivoon subcutaneousHCC1937 tumor model in mice. The underlying mechanism of combined therapy was determined withthe evaluation ofcH2AX foci. Combined therapy of ECT with bleomycin and olaparib potentiated theeffectiveness of ECT inBRCA1mutated HCC1937, but not in non-mutated HCC1143 cells. The combinedtherapy had a synergistic effect, which was due to the increased number of DNA double strand breaks.Addition of olaparib to ECT with bleomycinin vivoin HCC1937 tumor model had only minimal effect,indicating repetitive olaparib treatment would be needed. This study demonstrates that DNA repar inhibiting drugs, like olaparib, have the potential to increase the effectiveness of ECT with bleomycin. Keywords: electrochemotherapy, breast cancer, olaparib, bleomycin Published in DiRROS: 21.09.2022; Views: 681; Downloads: 269
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