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Abstract: 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.
Keywords: electrochemotherapy, IFN-alpha, melanoma
Published in DiRROS: 30.04.2024; Views: 35; Downloads: 5
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Abstract: 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.
Keywords: teeth microstructure, ameloblasts, ferritin, Fe-rich enamel, tomography, rodent
Published in DiRROS: 26.04.2024; Views: 44; Downloads: 12
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Abstract: Beyond growth parameters and drought tolerance, comparatively little is known about the functioning of different beech (Fagus sylvatica L.) provenances. We investigated properties of leaves, stem secondary xylem, and ectomycorrhiza (ECM), and explored their interdependencies to identify the best performing beech provenance in optimal growth conditions. The study was conducted on 23-year-old trees in a provenance trial. The investigated provenances originated from Atlantic (Belgium—BE), Alpine (Italy—IT, Slovenia—SI), and continental climates (the Czech Republic—CZ). A significant effect of provenance was observed for stem vessel diameters and conductive area, as well as for foliar %C, δ13C, δ15N, and δ18O. δ13C as a proxy of intrinsic water use efficiency (iWUE) showed that the highest iWUE was achieved in BE provenance. Individuals with a better iWUE had wider growth rings regardless of provenance. Better iWUE was associated with lower specific leaf area (SLA). ECM community composition and diversity indices did not differ significantly among the provenances. Specific ECM taxa were associated with individuals with high SLA, δ13C, δ15N, and δ18O. In optimal growth conditions with no stress events, BE is a promising provenance due to an efficient water conducting system with high vessel diameters and conductive area, and high iWUE, while Alpine provenances showed an adaptation of their water conducting system to freezing conditions at their original locations. Integrating findings from different compartments improves our understanding of functioning of different beech provenances.
Keywords: Fagus sylvatica, provenance trial, stable isotopes, specific leaf area, xylem vessels, ectomycorrhizal fungi
Published in DiRROS: 19.04.2024; Views: 71; Downloads: 38
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Abstract: Background. Electrochemotherapy is a tumour ablation modality, based on electroporation of the cell membrane, allowing non-permeant anticancer drugs to enter the cell, thus augmenting their cytotoxicity by orders of magnitude. In preclinical studies, bleomycin and cisplatin proved to be the most suitable for clinical use. Intravenous administration of cisplatin for electrochemotherapy is still not widely accepted in the clinics, presumably due to its lower antitumor effectiveness, but adjuvant therapy by immunomodulatory or vascular-targeting agents could provide a way for its potentiation. Hence, the aim of the present study was to explore the possibility of adjuvant tumour necrosis factor % (TNF-%) therapy to potentiate antitumor effectiveness of electrochemotherapy with intravenous cisplatin administration in murine sarcoma. Materials and methods. In vivo study was designed to evaluate the effect of TNF-% applied before or after the electrochemotherapy and to evaluate the effect of adjuvant TNF-% on electrochemotherapy with different cisplatin doses. Results. A synergistic interaction between TNF-% and electrochemotherapy was observed. Administration of TNF-% before the electrochemotherapy resulted in longer tumour growth delay and increased tumour curability, and was significantly more effective than TNF-% administration after the electrochemotherapy. Tumour analysis revealed increased platinum content in tumours, TNF-% induced blood vessel damage and increased tumour necrosis after combination of TNF-% and electrochemotherapy, indicating an anti-vascular action of TNF-%. In addition, immunomodulatory effect might have contributed to curability rate of the tumours. Conclusion. Adjuvant intratumoural TNF-% therapy synergistically contributes to electrochemotherapy with intravenous cisplatin administration. Due to its potentiation at all doses of cisplatin, the combined treatment is predicted to be effective also in tumours, where the drug concentration is suboptimal or in bigger tumours, where electrochemotherapy with intravenous cisplatin is not expected to be sufficiently effective.
Keywords: electrochemotherapy, TNF, adjuvant immunotherapy, cisplatin
Published in DiRROS: 17.04.2024; Views: 102; Downloads: 23
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Keywords: electrochemotherapy, cutaneous tumors, effectiveness, tumor size, meta-analysis
Published in DiRROS: 22.03.2024; Views: 101; Downloads: 32
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