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Iskalni niz: "ključne besede" (electrochemotherapy) .

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Numerical modeling in electroporation-based biomedical applications
Nataša Pavšelj, Damijan Miklavčič, 2008, izvirni znanstveni članek

Povzetek: Background. Numerous experiments have to be performed before a biomedical application is put to practical use in clinical environment. As a complementary work to in vitro, in vivo and medical experiments, we can use analytical and numerical models to represent, as realistically as possible, real biological phenomena of, in our case, electroporation. In this way we canevaluate different electrical parameters in advance, such as pulse amplitude, duration, number of pulses, or different electrode geometries. Suchnumerical models can contribute significantly to the understanding of an experiment and treatment planning as well as to the design of new electroporation devices and electrodes. Methods. We used commercially available modeling software, based on finite element method. We constructed a model of a subcutaneous tumor during electrochemotherapy (EMAS) and a model ofskin during gene electrotransfer (COMSOL Multiphysics). Tissue-electrode geometries, pulse parameters and currentvoltage measurements from in vivo experiments were used to develop and validate the models. Results. To describeadequately our in vivo observations, a tissue conductivity increase during electroporation was included in our numerical models. The output currents of the models were compared to the currents and the voltages measuredduring in vivo experiments and a good agreement was obtained. Also, when comparing the voltages needed for a successful electropermeabilization assuggested by the models, to voltages applied in experiments and achieving a successful electrochemotherapy or in vivo gene electrotransfer, good agreementcan be observed. Conclusions. Modeling of electric current and electric field distribution during cell and tissue electroporation proves to be helpful in describing different aspects of the process and allowing us to design electrodes and electroporation protocols as a part of treatment planning.
Ključne besede: electroporation, gene electrotransfer, electrochemotherapy, subcutaneous tumor, finite-element method
Objavljeno v DiRROS: 07.03.2024; Ogledov: 63; Prenosov: 22
.pdf Celotno besedilo (549,62 KB)

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Combination of pembrolizumab with electrochemotherapy in cutaneous metastases from melanoma : a comparative retrospective study from the InspECT and Slovenian Cancer Registry
Luca Giovanni Campana, Barbara Perić, Matteo Mascherini, Romina Spina, Christian Kunte, Erika Kis, Petra Rozsa, Pietro Quaglino, Maja Čemažar, Maša Bošnjak, Gregor Serša, 2021, izvirni znanstveni članek

Povzetek: Electrochemotherapy (ECT) is an effective locoregional therapy for cutaneous melanoma metastases and has been safely combined with immune checkpoint inhibitors in preliminary experiences. Since ECT is known to induce immunogenic cell death, its combination with immune checkpoint inhibitors might be beneficial. In this study, we aimed to investigate the effectiveness of ECT on cutaneous melanoma metastases in combination with pembrolizumab. We undertook a retrospective matched cohort analysis of stage IIIC%IV melanoma patients, included in the International Network for sharing practices of ECT (InspECT) and the Slovenian Cancer Registry. We compared the outcome of patients who received the following treatments: (a) pembrolizumab alone, (b) pembrolizumab plus ECT, and (c) ECT. The groups were matched for age, sex, performance status, and size of skin metastases. The local objective response rate (ORR) was higher in the pembrolizumab-ECT group than in the pembrolizumab group (78% and 39%, p < 0.001). The 1 year local progression-free survival (LPFS) rates were 86% and 51% (p < 0.001), and the 1 year systemic PFS rates were 64% and 39%, respectively (p = 0.034). The 1 year overall survival (OS) rates were 88% and 64%, respectively (p = 0.006). Our results suggest that skin-directed therapy with ECT improves superficial tumor control in melanoma patients treated with pembrolizumab. Interestingly, we observed longer PFS and OS in the pembrolizumab-ECT group than in the pembrolizumab group. These findings warrant prospective confirmation.
Ključne besede: electrochemotherapy, metastatic melanoma, skin metastases
Objavljeno v DiRROS: 10.10.2022; Ogledov: 434; Prenosov: 219
.pdf Celotno besedilo (701,05 KB)
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Biological factors of the tumour response to electrochemotherapy : review of the evidence and a research roadmap
Gregor Serša, Katja Uršič Valentinuzzi, Maja Čemažar, Richard Heller, Maša Bošnjak, Luca Giovanni Campana, 2021, pregledni znanstveni članek

Povzetek: 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.
Ključne besede: biological factors, biomarkers, electrochemotherapy, bleomycin, cisplatin
Objavljeno v DiRROS: 23.09.2022; Ogledov: 496; Prenosov: 149
.pdf Celotno besedilo (1,32 MB)

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Electrochemotherapy in mucosal cancer of the head and neck : a systematic review
Primož Strojan, Aleš Grošelj, Gregor Serša, Christina Caroline Plaschke, Jan B. Vermorken, Sandra Nuyts, Remco De Bree, Avraham Eisbruch, William M. Mendenhall, Robert Smee, Alfio Ferlito, 2021, pregledni znanstveni članek

Povzetek: Electrochemotherapy (ECT) is a local ablative treatment that is based on the reversible electroporation and intracellular accumulation of hydrophilic drug molecules, which greatly increases their cytotoxicity. In mucosal head and neck cancer (HNC), experience with ECT is limited due to the poor accessibility of tumors. In order to review the experience with ECT in mucosal HNC, we undertook a systematic review of the literature. In 22 articles, published between 1998 and 2020, 16 studies with 164 patients were described. Curative and palliative intent treatment were given to 36 (22%) and 128 patients (78%), respectively. The majority of tumors were squamous cell carcinomas (79.3%) and located in the oral cavity (62.8%). In the curative intent group, complete response after one ECT treatment was achieved in 80.5% of the patients, and in the palliative intent group, the objective (complete and partial) response rate was 73.1% (31.2% and 41.9%). No serious adverse events were reported during or soon after ECT and late effects were rare (19 events in 17 patients). The quality-of-life assessments did not show a significant deterioration at 12 months post-ECT. Provided these preliminary data are confirmed in randomized controlled trials, ECT may be an interesting treatment option in selected patients with HNC not amenable to standard local treatment.
Ključne besede: electrochemotherapy, head and neck cancer, mucosal cancer
Objavljeno v DiRROS: 23.09.2022; Ogledov: 513; Prenosov: 237
.pdf Celotno besedilo (1,03 MB)
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Potentiation of electrochemotherapy effectiveness by immunostimulation with IL-12 gene electrotransfer in mice is dependent on tumor immune status
Katja Uršič Valentinuzzi, Špela Kos, Urška Kamenšek, Maja Čemažar, Simona Miceska, Boštjan Markelc, Simon Buček, Barbara Starešinič, Veronika Kloboves-Prevodnik, Richard Heller, Gregor Serša, 2021, izvirni znanstveni članek

Povzetek: Electrochemotherapy (ECT) exhibits high therapeutic effectiveness in the clinic, achieving up to 80% local tumor control but without a systemic (abscopal) effect. Therefore, we designed a combination therapy consisting of ECT via intratumoral application of bleomycin, oxaliplatin or cisplatin with peritumoral gene electrotransfer of a plasmid encoding interleukin-12 (p. t. IL-12 GET). Our hypothesis was that p. t. IL-12 GET potentiates the effect of ECT on local and systemic levels and that the potentiation varies depending on tumor immune status. Therefore, the combination therapy was tested in three immunologically different murine tumor models. In poorly immunogenic B16F10 melanoma, IL-12 potentiated the antitumor effect of ECT with biologically equivalent low doses of cisplatin, oxaliplatin or bleomycin. The most pronounced potentiation was observed after ECT using cisplatin, resulting in a complete response rate of 38% and an abscopal effect. Compared to B16F10 melanoma, better responsiveness to ECT was observed in more immunogenic 4%T1 mammary carcinoma and CT26 colorectal carcinoma. In both models, p. t. IL-12 GET did not significantly improve the therapeutic outcome of ECT using any of the chemotherapeutic drugs. Collectively, the effectiveness of the combination therapy depends on tumor immune status. ECT was more effective in more immunogenic tumors, but GET exhibited greater contribution in less immunogenic tumors. Thus, the selection of the therapy, namely, either ECT alone or combination therapy with p. t. IL-12, should be predominantly based on tumor immune status.
Ključne besede: electrochemotherapy, gene electrotransfer, interleukin-12
Objavljeno v DiRROS: 21.09.2022; Ogledov: 527; Prenosov: 185
.pdf Celotno besedilo (7,82 MB)

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PARP inhibitor olaparib has a potential to increase the effectiveness of electrochemotherapy in BRCA1 mutated breast cancer in mice
Maša Bošnjak, Tanja Jesenko, Boštjan Markelc, Larisa Janžič, Maja Čemažar, Gregor Serša, 2021, izvirni znanstveni članek

Povzetek: 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.
Ključne besede: electrochemotherapy, breast cancer, olaparib, bleomycin
Objavljeno v DiRROS: 21.09.2022; Ogledov: 488; Prenosov: 168
.pdf Celotno besedilo (3,74 MB)

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