51. Statistical approach to interpretation of geochemical data of stream sediment in Pleše mining areaSimona Jarc, 2022, original scientific article Abstract: The Ba, Pb and Zn ore deposit Pleše near Ljubljana is one of the formerly productive mines. The stream sediments were sampled and analysed by XRF to establish the effect of grain size, mineralization, and downstream location of sampling sites on geochemical composition based on various statistical analyses. Statistical analyses of the geochemical data confirm the impact of mineralization. The parametric t-test, non-parametric Mann-Whitney test and cluster analysis showed only minor differences in the geochemical composition of the samples with different grain sizes (< 0.063 mm and 0.063-2 mm). The parametric and non-parametric correlation coefficients as well as cluster analysis indicate that the contents of Si, Al, K, Rb, and Fe are associated with weathered rock forming minerals such as micas, and clay minerals, whereas Nb and Zr are associated with minerals resistant to weathering. Ca and Mg are associated with carbonates. S, Ba, Sr, Pb, Zn, and Mn indicate local mineralization with sulphates and sulphides. The results of the t-test and analysis of variance, Mann-Whitney tests and Kruskal-Wallis ANOVA of the groups established by the cluster analysis confirm that the contents of Ba, Pb and Sr have a statistically significant influence on the classification of the cluster group - i.e., the influence of sediment mineralization. There are no differences in elemental contents in the sediment samples downstream. The statistical approach to evaluate the geochemical data has proven useful and provides a good basis for further interpretation.
Keywords: ANOVA, t-test, correlation, cluster analysis, XRF, mineralization
Published in DiRROS: 18.01.2023; Views: 460; Downloads: 212
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52. Sistemsko zdravljenje raka dojkSimona Borštnar, 2022, published professional conference contribution Abstract: Sedemdeseta leta prejšnjega stoletja so bila obdobje velikih sprememb na področju raka dojk, v smislu teoretičnega dojemanja narave raka dojk in drugačnega pristopa k zdravljenju. Teorijo, da je rak lokalna bolezen, je nadomestila teorija o raku dojk kot sistemski bolezni. Sistemsko zdravljenje, ki je bilo do takrat omejeno zgolj na uporabo pri razsejani bolezni, je kot dopolnilno zdravljenje postalo del zdravljenja večine bolnic z zgodnjim rakom dojk.
Razvoj molekularne onkologije, dekodiranje človeškega genoma in uporaba bioinformatike pa sta v preteklega četrt stoletja na široko odprla vrata novim spoznanjem in dodatno spremenila možnosti v zdravljenju raka dojk. Smo v obdobju personalizirane medicine, kjer se o zdravljenju odločamo na podlagi lastnosti rakavih celic in pri tem uporabljamo široko paleto zdravil: hormonsko
zdravljenje, kemoterapijo, različna tarčna zdravila v obliki malih molekul, monoklonskih protiteles in konjugatov monoklonskih protiteles s citostatiki ter imunoterapijo z zaviralci imunskih nadzornih točk.
Keywords: sistemsko zdravljenje, rak dojke, bolniki
Published in DiRROS: 22.12.2022; Views: 304; Downloads: 71
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53. Gene electrotransfer of IL-2 and IL-12 plasmids effectively eradicated murine B16.F10 melanomaTilen Komel, Maša Omerzel, Simona Kranjc Brezar, Mariangela De Robertis, M. Mastrodonato, G. Scillitani, G. Pesole, Emanuella Signori, Gregor Serša, Maja Čemažar, 2021, original scientific article Abstract: Gene therapy has become an important approach for treating cancer, and electroporation represents a technology for introducing therapeutic genes into a cell. An example of cancer gene therapy relying on gene electrotransfer is the use of immunomodulatory cytokines, such as interleukin 2 (IL-2) and 12 (IL-12), which directly stimulate immune cells at the tumour site. The aim of our study was to determine the effects of gene electrotransfer with two plasmids encoding IL-2 and IL-12 in vitro and in vivo. Two different pulse protocols, known as EP1 (600 V/cm, 5 ms, 1 Hz, 8 pulses) and EP2 (1300 V/cm, 100 %s, 1 Hz, 8 pulses), were assessed in vitro for application in subsequent in vivo experiments. In the in vivo experiment, gene electrotransfer of pIL-2 and pIL-12 using the EP1 protocol was performed in B16.F10 murine melanoma. Combined treatment of tumours using pIL2 and pIL12 induced significant tumour growth delay and 71% complete tumour regression. Furthermore, in tumours coexpressing IL-2 and IL-12, increased accumulation of dendritic cells and M1 macrophages was obtained along with the activation of proinflammatory signals, resulting in CD4 + and CD8 + T-lymphocyte recruitment and immune memory development in the mice. In conclusion, we demonstrated high antitumour efficacy of combined IL-2 and IL-12 gene electrotransfer protocols in low-immunogenicity murine B16.F10 melanoma.
Keywords: gene therapy, gene electrotransfer, IL-12, immunotherapy, melanoma
Published in DiRROS: 23.09.2022; Views: 610; Downloads: 184
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55. Contrast-enhanced ultrasound for evaluation of tumor perfusion and outcome following treatment in a murine melanoma modelMaja Brložnik, Nina Boc, Maja Čemažar, Maša Omerzel, Monika Savarin, Nataša Kejžar, Gregor Serša, Darja Pavlin, Simona Kranjc Brezar, 2021, original scientific article Published in DiRROS: 23.09.2022; Views: 480; Downloads: 292
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56. Potentiation of electrochemotherapy effectiveness by immunostimulation with IL-12 gene electrotransfer in mice is dependent on tumor immune statusKatja Uršič Valentinuzzi, Špela Kos, Urška Kamenšek, Maja Čemažar, Simona Miceska, Boštjan Markelc, Simon Buček, Barbara Starešinič, Veronika Kloboves-Prevodnik, Richard Heller, Gregor Serša, 2021, original scientific article Abstract: 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.
Keywords: electrochemotherapy, gene electrotransfer, interleukin-12
Published in DiRROS: 21.09.2022; Views: 570; Downloads: 197
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57. Gene electrotransfer of proinflammatory chemokines CCL5 and CCL17 as a novel approach of modifying cytokine expression profile in the tumor microenvironmentTim Božič, Gregor Serša, Simona Kranjc Brezar, Maja Čemažar, Boštjan Markelc, 2021, original scientific article Abstract: The effectiveness of immunotherapy highly correlates with the degree and the type of infiltrated immune cells in the tumor tissue. Treatments based on modifying the immune cell infiltrate of the tumor microenvironment are thus gaining momentum. Therefore, the aim of our study was to investigate the effects of gene therapy with two proinflammatory chemokines CCL5 and CCL17 on inflammatory cytokine expression profile and immune cell infiltrate in two murine breast tumor models, 4T1 and E0771, and two murine colon tumor models, CT26 and MC38. In vitro, lipofection of plasmid DNA encoding CCL5 or CCL17 resulted in changes in the cytokine expression profile similar to control plasmid DNA, implying that the main driver of these changes was the entry of foreign DNA into the cell%s cytosol. In vivo, gene electrotransfer resulted in high expression levels of both Ccl5 and Ccl17 transgenes in the 4T1 and CT26 tumor models. Besides a minor increase in the survival of the treated mice, the therapy also resulted in increased expression of Cxcl9 and Ifn%, potent activators of the immune system, in CT26 tumors. However, this was not recapitulated in changes of TME, implying that a further refinement of the dosing schedule is needed.
Keywords: chemokines, cytokine expression, gene electrotransfer, CCL5
Published in DiRROS: 19.09.2022; Views: 532; Downloads: 157
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58. Estimating quantitative physiological and morphological tissue parameters of murine tumor models using hyperspectral imaging and optical profilometryTadej Tomanič, Luka Rogelj, Jošt Stergar, Boštjan Markelc, Tim Božič, Simona Kranjc Brezar, Gregor Serša, Matija Milanič, 2022, original scientific article Abstract: Understanding tumors and their micro-environment are essential for successfuland accurate disease diagnosis. Tissuephysiology and morphology are altered intumors compared to healthy tissues, andthere is a need to monitor tumors and their surrounding tissues, includingblood vessels, non-invasively. This preliminary study utilizes a multimodaloptical imaging system combining hyperspectral imaging (HSI) and three-dimensional (3D) optical profilometry (OP) to capture hyperspectral imagesand surface shapes of subcutaneously grown murine tumor models. Hyper-spectral images are corrected with 3D OP data and analyzed using the inverse-adding doubling (IAD) method to extract tissue properties such as melaninvolume fraction and oxygenation. Blood vessels are segmented using theB-COSFIRE algorithm from oxygenation maps. From 3D OP data, tumor vol-umes are calculated and compared to manual measurements using a verniercaliper. Results show that tumors can be distinguished from healthy tissuebased on most extracted tissue parameters (p<0:05). Furthermore, blood oxy-genation is 50% higher within the blood vessels than in the surrounding tissue,and tumor volumes calculated using 3D OP agree within 26% with manualmeasurements using a vernier caliper. Results suggest that combining HSI andOP could provide relevant quantitative information about tumors and improvethe disease diagnosis.
Keywords: medical physics, hyperspectral imaging, diffuse reflectance spectroscopy, blood vessels, tumors
Published in DiRROS: 08.09.2022; Views: 549; Downloads: 191
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59. In vitro and in vivo correlation of skin and cellular responses to nucleic acid deliveryMaša Omerzel, Katarina Žnidar, A. Sales Conniff, Tanja Jesenko, Boštjan Markelc, Jared Tur, Nina Semenova, Kristopher Kohena, Simona Kranjc Brezar, Loree C. Heller, Maja Čemažar, 2022, original scientific article Abstract: Skin, the largest organ in the body, provides a passive physical barrier against infection and contains elements of the innate and adaptive immune systems. Skin consists of various cells, including keratinocytes, fibroblasts, endothelial cells and immune cells. This diversity of cell types could be important to gene therapies because DNA transfection could elicit different responses in different cell types. Previously, we observed the upregulation and activation of cytosolic DNA sensing pathways in several non-tumor and tumor cell types as well in tumors after the electroporation (electrotransfer) of plasmid DNA (pDNA). Based on this research and the innate immuno- genicity of skin, we correlated the effects of pDNA electrotransfer to fibroblasts and keratinocytes to mouse skin using reverse transcription real-time PCR (RT-qPCR) and several types of protein quantification. After pDNA electrotransfer, the mRNAs of the putative DNA sensors DEAD (AspGlu-Ala-Asp) box polypeptide 60 (Ddx60), absent in melanoma 2 (Aim2), Z-DNA binding protein 1 (Zbp1), interferon activated gene 202 (Ifi202), and interferon-inducible protein 204 (Ifi204) were upregulated in keratinocytes, while Ddx60, Zbp1 and Ifi204 were upregulated in fibroblasts. Increased levels of the mRNAs and proteins of several cytokines and chemokines were detected and varied based on cell type. Mouse skin experiments in vivo confirmed our in vitro results with increased expression of putative DNA sensor mRNAs and of the mRNAs and proteins of several cytokines and chemokines.
Keywords: DNA sensors, cytokines, electrotransfer, skin
Published in DiRROS: 06.09.2022; Views: 583; Downloads: 301
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60. Evaluation of thermal conductivity estimation models with laboratory-measured thermal conductivities of sedimentsSimona Adrinek, Rao Martand Singh, Mitja Janža, Mateusz Żeruń, Grzegorz Ryżyński, 2022, original scientific article Abstract: Thermal conductivity is one of the key parameters for estimating low-temperature geothermal potential. In addition to field techniques, it can be determined based on physical parameters of the sediment measured in the laboratory. Following the methodology for cohesive and non-cohesive sample preparation, laboratory measurements were carried out on 30 samples of sediments. Density, porosity and water content of samples were measured and used in thermal conductivity estimation models (TCEM). The bulk thermal conductivity (λb) calculated with six TCEMs was compared with the measured λb to evaluate the predictive capacity of the analytical methods used. The results show that the empirical TCEMs are suitable to predict the λb of the analysed sediment types, with the standard deviation of the residuals (RMSE) ranging from 0.11 to 0.35 Wm−1 K−1. To improve the fit, this study provides a new modified parameterisation of two empirical TCEMs (Kersten and Côté&Konrad model) and, therefore, suggests the most suitable TCEMs for specific sample conditions. The RMSE ranges from 0.11 to 0.29 Wm−1 K−1. Mixing TCEM showed an RMSE of up to 2.00 Wm−1 K−1, meaning they are not suitable for predicting sediment λb. The study provides an insight into the analytical determination of thermal conductivity based on the physical properties of sediments. The results can help to estimate the low-temperature geothermal potential more quickly and easily and promote the sustainable use of this renewable energy source, which has applications in environmental and engineering science.
Keywords: thermal conductivity, non-cohesive sediment, cohesive sediment, estimation model
Published in DiRROS: 25.08.2022; Views: 558; Downloads: 252
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