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Abstract: 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.
Keywords: gene therapy, electrotransfer, plasmid, irradiation, immune response, melanoma
Published in DiRROS: 24.05.2024; Views: 159; Downloads: 142
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Keywords: varstvo gozdov, morfološke analize, PP Geosmithia morbida, bolezen tisočerih rakov, vektorji, rtPCR
Published in DiRROS: 23.05.2024; Views: 108; Downloads: 0
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Keywords: varstvo gozdov, morfološke analize, PP Anoplophora glabripennis, rastlinski vzorci
Published in DiRROS: 23.05.2024; Views: 125; Downloads: 0
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Abstract: The accurate textural characterization of mantle xenoliths is one of the fundamental steps to understanding the main processes occurring in the upper mantle, such as sub-solidus recrystallization, magmatic crystallization, and metasomatism. Texture, composition, and mineralogy reflect the temperature, pressure, stress conditions, melting, and/or contamination events undergone before and during the entrapment in the host magma. For these reasons, characterizing the three-dimensional (3D) texture of silicate, oxide, sulfide, and glass phases has great importance in the study of mantle xenoliths. We performed a multi-scale and multi-modal 3D textural analysis based on X-ray computed microtomography (µ-CT) data of three mantle xenoliths from different geodynamic settings (i.e., mobile belt zone, pericraton, oceanic hotspot). The samples were selected to represent different, variably complex internal structures composed of grains of different phases, fractures, voids, and fluid inclusions of different sizes. We used an approach structured in increasing steps of spatial and contrast resolution, starting with in-house X-ray µ-CT imaging (spatial resolution from 30 µm down to 6.25 µm) and moving to high-resolution synchrotron X-ray µ-CT at the micrometer scale. We performed a 3D characterization of mantle xenoliths, comparing the results with the analysis of conventional 2D images (thin sections) obtained by optical microscopy and simulating the random sectioning of several thin sections to estimate the probability of correct modal classification. The 3D models allow the extraction of textural information that cannot be quantified solely from thin sections: spinel layering, distribution of silicic glass, and related vesicles. Moreover, high-density volumes identified as sulfides were detected in two xenoliths, showing no relation with the spinel layering in one case and a preferential concentration along fractures in the other. Given the variety of textures and mineral assemblages of mantle xenoliths worldwide, the results are used to suggest experimental and analytical protocols for the characterization of these materials.
Keywords: petrology, mantle xenoliths, X-ray microtomography, multi-scale image analysis
Published in DiRROS: 23.05.2024; Views: 82; Downloads: 18
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Keywords: varstvo gozdov, morfološke analize, PP Geosmithia morbida, bolezen tisočerih rakov, rastlinski vzorec, rtPCR
Published in DiRROS: 23.05.2024; Views: 130; Downloads: 0
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