1. Electrotransfer of plasmid DNA radiosensitizes B16F10 tumors through activation of immune responseMonika Savarin, Urška Kamenšek, Maja Čemažar, Richard Heller, Gregor Serša, 2017, izvirni znanstveni članek Povzetek: Tumor irradiation combined with adjuvant treatments, either vascular targeted or immunomodulatory, is under intense investigation. Gene electrotransfer of therapeutic genes is one of these approaches. The aim of this study was to determine, whether gene electrotransfer of plasmid encoding shRNA for silencing endoglin, with vascular targeted effectiveness, can radiosensitize melanoma B16F10 tumors. Materials and methods. The murine melanoma B16F10 tumors, growing on the back of C57Bl/6 mice, were treated by triple gene electrotransfer and irradiation. The antitumor effect was evaluated by determination of tumor growth delay and proportion of tumor free mice. Furthermore, histological analysis of tumors (necrosis, apoptosis, proliferation, vascularization, presence of hypoxia and infiltration of immune cells,) was used to evaluate the therapeutic mechanisms. Results. Gene electrotransfer of plasmid silencing endoglin predominantly indicated vascular targeted effects of the therapy, since significant tumor growth delay and 44% of tumor free mice were obtained. In addition, irradiation had minor effects on radioresistant melanoma, with 11% of mice tumor free. The combined treatment resulted in excellent effectiveness with 88% of mice tumor free, with more than half resistant to secondary tumor challenge, which was observed also with the plasmid devoid of the therapeutic gene. Histological analysis of tumors in the combined treatment group, demonstrated similar mode of action of the gene electrotransfer of plasmid encoding shRNA for silencing endoglin and devoid of it, both through the induction of an immune response. Conclusions. The results of this study indicate that irradiation can in radioresistant melanoma tumors, by release of tumor associated antigens, serve as activator of the immune response, besides directly affecting tumor cells and vasculature. The primed antitumor immune response can be further boosted by gene electrotransfer of plasmid, regardless of presence of the therapeutic gene, which was confirmed by the high radiosensitization, resulting in prolonged tumor growth delay and 89% of tumor free mice that were up to 63% resistant to secondary challenge of tumor. In addition, gene electrotransfer of therapeutic plasmid for silencing endoglin has also a direct effect on tumor vasculature and tumors cells; however in combination with radiotherapy this effect was masked by pronounced immune response.
Ključne besede: gene therapy, electrotransfer, plasmid, irradiation, immune response, melanoma
Objavljeno v DiRROS: 24.05.2024; Ogledov: 79; Prenosov: 32
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4. Accelerated drought-induced resilience decline across European forestsAllan Buras, Benjamin Meyer, Konstantin Gregor, Lucia Layritz, Jernej Jevšenak, Christian Zang, Anja Rammig, 2024, objavljeni povzetek znanstvenega prispevka na konferenci Ključne besede: Europe, drought, forest, Europe
Objavljeno v DiRROS: 14.05.2024; Ogledov: 120; Prenosov: 87
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6. Electrochemotherapy by pulsed electromagnetic field treatment (PEMF) in mouse melanoma B16F10 in vivoSimona Kranjc Brezar, Matej Kranjc, Janez Ščančar, Jure Jelenc, Gregor Serša, Damijan Miklavčič, 2016, izvirni znanstveni članek Ključne besede: pulsed electromagnetic field, bipolar pulses, contactless electroporation, CDDP, electrochemotherapy, mouse melanoma
Objavljeno v DiRROS: 09.05.2024; Ogledov: 93; Prenosov: 61
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7. Electrochemotherapy with bleomycin is effective in BRAF mutated melanoma cells and interacts with BRAF inhibitorsTanja Jesenko, Lara Prosen, Maja Čemažar, Tjaša Potočnik, Gregor Serša, 2016, izvirni znanstveni članek Povzetek: The aim of the study was to explore the effectiveness of electrochemotherapy (ECT) during the treatment of melanoma patients with BRAF inhibitors. Its effectiveness was tested on BRAF mutated and non-mutated melanoma cells in vitro and in combination with BRAF inhibitors. Materials and methods. ECT with bleomycin was performed on two human melanoma cell lines, with (SK-MEL-28) or without (CHL-1) BRAF V600E mutation. Cell survival was determined using clonogenic assay to determine the effectiveness of ECT in melanoma cells of different mutation status. Furthermore, the effectiveness of ECT in concomitant treatment with BRAF inhibitor vemurafenib was also determined in BRAF mutated cells SK-MEL-28 with clonogenic assay. Results. The survival of BRAF V600E mutated melanoma cells was even lower than non-mutated cells, indicating that ECT is effective regardless of the mutational status of melanoma cells. Furthermore, the synergistic interaction between vemurafenib and ECT with bleomycin was demonstrated in the BRAF V600E mutated melanoma cells. Conclusions. The effectiveness of ECT in BRAF mutated melanoma cells as well as potentiation of its effectiveness during the treatment with vemurafenib in vitro implies on clinical applicability of ECT in melanoma patients with BRAF mutation and/or during the treatment with BRAF inhibitors.
Ključne besede: electrochemotherapy, BRAF inhibitors, vemurafenib, melanoma
Objavljeno v DiRROS: 30.04.2024; Ogledov: 160; Prenosov: 36
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8. Effectiveness of electrochemotherapy after IFN-[alpha] adjuvant therapy of melanoma patientsAndrejc Hribernik, Maja Čemažar, Gregor Serša, Maša Omerzel, Marko Snoj, 2016, izvirni znanstveni članek Povzetek: The combination of electrochemotherapy with immuno-modulatory treatments has already been explored and proven effective. However, the role of interferon alpha (IFN-alpha) adjuvant therapy of melanoma patients and implication on electrochemotherapy effectiveness has not been explored yet. Therefore, the aim of the study was to retrospectively evaluate the effectiveness and safety of electrochemotherapy after the previous adjuvant treatment with IFN-alpha in melanoma patients. Patients and methods. The study was a retrospective single-center observational analysis of the patients with advanced melanoma, treated with electrochemotherapy after previous IFN-alpha adjuvant therapy. Five patients, treated between January 2008 and December 2014, were included into the study, regardless of the time point of IFN-alpha adjuvant therapy. Results. Electrochemotherapy of recurrent melanoma after the IFN-alpha adjuvant therapy proved to be a safe and effective treatment. Patients with one or two metastases responded completely. Among patients with multiple metastases, there was a variable response rate. In one patient all 23 metastases responded completely, in second patient more than 85% of all together 80 metastases responded completely and in third patient all 5 metastases had partial response. Taking into account all metastases from all patients together there was an 85% complete response rate. Conclusions. The study showed that electrochemotherapy of recurrent melanoma after the IFN-alpha adjuvant therapy is a safe and effective treatment modality, which results in a high complete response rate, not only in single metastasis, but also in multiple metastases. The high complete response rate might be due to an IFN-alpha immune-editing effect, however, further studies with a larger number of patients are needed to support this presumption.
Ključne besede: electrochemotherapy, IFN-alpha, melanoma
Objavljeno v DiRROS: 30.04.2024; Ogledov: 106; Prenosov: 33
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10. Ingenious architecture and coloration generation in enamel of Rodent teethVesna Šrot, Sophia Houari, Gregor Kapun, Birgit Bußmann, Felicitas Predel, Boštjan Pokorny, Elena Bužan, Ute Salzberger, Bernhard Fenk, Marion Kelsch, Peter van Aken, 2024, izvirni znanstveni članek Povzetek: Teeth exemplify architectures comprising an interplay of inorganic and organic constituents, resulting in sophisticated natural composites. Rodents (Rodentia) showcase extraordinary adaptations, with their continuously growing incisors surpassing human teeth in functional and structural optimizations. In this study, employing state-of-the-art direct atomic-scale imaging and nanoscale spectroscopies, we present compelling evidence that the release of material from ameloblasts and the subsequent formation of iron-rich enamel and surface layers in the constantly growing incisors of rodents are complex orchestrated processes, intricately regulated and independent of environmental factors. The synergistic fusion of three-dimensional tomography and imaging techniques of etched rodent́s enamel unveils a direct correlation between the presence of pockets infused with ferrihydrite-like material and the acid resistant properties exhibited by the iron-rich enamel, fortifying it as an efficient protective shield. Moreover, observations using optical microscopy shed light on the role of iron-rich enamel as a microstructural element that acts as a path for color transmission, although the native color remains indistinguishable from that of regular enamel, challenging the prevailing paradigms. The redefinition of “pigmented enamel” to encompass ferrihydrite-like infusion in rodent incisors reshapes our perception of incisor microstructure and color generation. The functional significance of acid-resistant iron-rich enamel and the understanding of the underlying coloration mechanism in rodent incisors have far-reaching implications for human health, development of potentially groundbreaking dental materials, and restorative dentistry. These findings enable the creation of an entirely different class of dental biomaterials with enhanced properties, inspired by the ingenious designs found in nature.
Ključne besede: teeth microstructure, ameloblasts, ferritin, Fe-rich enamel, tomography, rodent
Objavljeno v DiRROS: 26.04.2024; Ogledov: 146; Prenosov: 122
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