71. Biological factors of the tumour response to electrochemotherapy : review of the evidence and a research roadmapGregor Serša, Katja Uršič Valentinuzzi, Maja Čemažar, Richard Heller, Maša Omerzel, 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: 520; Prenosov: 159
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72. 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, 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: 558; Prenosov: 194
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73. Mutational burden, MHC-I expression and immune infiltration as limiting factors for in situ vaccination by TNF[alfa] and IL-12 gene electrotransferUrška Kamenšek, Katja Uršič Valentinuzzi, Boštjan Markelc, Maja Čemažar, Vita Šetrajčič Dragoš, Gregor Serša, 2021, izvirni znanstveni članek Povzetek: In situ vaccination is a promising immunotherapeutic approach, where various local ablative therapies are used to induce an immune response against tumor antigens that are released from the therapy-killed tumor cells. We recently proposed using intratumoral gene electrotransfer for concomitant transfection of a cytotoxic cytokine tumor necrosis factor-% (TNF%) to induce in situ vaccination, and an immunostimulatory cytokine interleukin 12 (IL-12) to boost the primed immune response. Here, our aim was to test the local and systemic effectiveness of the approach in tree syngeneic mouse tumor models and associate it with tumor immune profiles, characterized by tumor mutational burden, immune infiltration and expression of PD-L1 and MHC-I on tumor cells. While none of the tested characteristic proved predictive for local effectiveness, high tumor mutational burden, immune infiltration and MHC-I expression were associated with higher abscopal effectiveness. Hence, we have confirmed that both the abundance and presentation of tumor antigens as well as the absence of immunosuppressive mechanisms are important for effective in situ vaccination. These findings provide important indications for future development of in situ vaccination based treatments, and for the selection of tumor types that will most likely benefit from it.
Ključne besede: in situ vaccination, gene electrotransfer, interleukin 12, tumor necrosis factor [alfa]
Objavljeno v DiRROS: 19.09.2022; Ogledov: 519; Prenosov: 174
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74. Poročilo 2021 o izvajanju letnega programa dela javnih služb v oljkarstvuMaja Podgornik, Viljanka Vesel, Dunja Bandelj, Bojan Butinar, Elizabeta Bonin, Janko Brajnik, Erika Bešter, Jakob Fantinič, Katja Fičur, Vasja Juretič, Matjaž Prinčič, Vasilij Valenčič, Saša Volk, Milena Bučar-Miklavčič, 2022, druge monografije in druga zaključena dela Povzetek: V okviru javne službe za izvajanje strokovnih nalog v oljkarstvu, so bile v letu 2021 izvedene naloge: selekcija, introdukcija, razmnoževanje sadilnega material, ugotavljanje ustreznih tehnologije za pridelavo oljk ter ugotavljanje vrednosti oljk za predelavo. V poročilu so zbrane morfološke in agronomske lastnosti ter značilnosti oljčnega olja sort 'Mata', 'Coratina', 'Frantoio', 'Oblica', 'Pendolino', 'Picholine' in 'Grignan' za opazovanja v letu 2021. Predstavljeni so tudi rezultati genotipizacije izbranih sort ter agronomskega vrednotenja in fenofaze različnih sort, ki so zasajene v introdukcijsko-kolekcijskem nasadu Purissima in Šempeter. V poročilu so zbrani podatki tehnoloških poskusov pridelave in predelave; parametri, ki karakterizirajo posamezna sortna olja ter parametri kakovosti oljčnega olja letnika 2021.
Ključne besede: oljkarstvo, oljka, oljčno olje, tehnologija pridelave, ocena letnika, introdukcija, selekcija
Ključne besede: elektronske knjige
Objavljeno v DiRROS: 14.09.2022; Ogledov: 635; Prenosov: 312
Celotno besedilo (5,04 MB)
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75. Tumor cell-based vaccine contributes to local tumor irradiation by eliciting a tumor model-dependent systemic immune responseTinkara Remic, Gregor Serša, Kristina Levpušček, Urša Lampreht Tratar, Katja Uršič Valentinuzzi, Andrej Cör, Urška Kamenšek, 2022, izvirni znanstveni članek Povzetek: Multimodal treatment approaches, such as radio-immunotherapy, necessitate regimen optimization and the investigation of the interactions of different modalities. The aim of this study was two-fold. Firstly, to select the most effective combination of irradiation and the previously developed tumor cell-based vaccine and then to provide insight into the immune response to the selected combinatorial treatment. The study was performed in immunologically different murine tumor models: B16F10 melanoma and CT26 colorectal carcinoma. The most effective combinatorial treatment was selected by comparing three different IR regimens and three different vaccination regimens. We determined the local immune response by investigating immune cell infiltration at the vaccination site and in tumors. Lastly, we determined the systemic immune response by investigating the amount of tumor-specific effector lymphocytes in draining lymph nodes. The selected most effective combinatorial treatment was 5× 5 Gy in combination with concomitant single-dose vaccination (B16F10) or with concomitant multi-dose vaccination (CT26). The combinatorial treatment successfully elicited a local immune response at the vaccination site and in tumors in both tumor models. It also resulted in the highest amount of tumor-specific effector lymphocytes in draining lymph nodes in the B16F10, but not in the CT26 tumor-bearing mice. However, the amount of tumor-specific effector lymphocytes was intrinsically higher in the CT26 than in the B16F10 tumor model. Upon the selection of the most effective combinatorial treatment, we demonstrated that the vaccine elicits an immune response and contributes to the antitumor efficacy of tumor irradiation. However, this interaction is multi-faceted and appears to be dependent on the tumor immunogenicity.
Ključne besede: experimental oncology, multimodal treatment, radio-imunotherapy
Objavljeno v DiRROS: 14.09.2022; Ogledov: 540; Prenosov: 282
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76. Quantitative imaging biomarkers of immune-related adverse events in immune-checkpoint blockade-treated metastatic melanoma patients : a pilot studyNežka Hribernik, Daniel T. Huff, Andrej Studen, Katarina Zevnik, Žan Klaneček, Hamid Emamekhoo, Katja Škalič, Robert Jeraj, Martina Reberšek, 2022, izvirni znanstveni članek Povzetek: Purpose: To develop quantitative molecular imaging biomarkers of immune-related adverse event (irAE) development in malignant melanoma (MM) patients receiving immune-checkpoint inhibitors (ICI) imaged with 18F-FDG PET/CT. Methods: 18F-FDG PET/CT images of 58 MM patients treated with anti-PD-1 or anti-CTLA-4 ICI were retrospectively analyzed for indication of irAE. Three target organs, most commonly affected by irAE, were considered: bowel, lung, and thyroid. Patient charts were reviewed to identify which patients experienced irAE, irAE grade, and time to irAE diagnosis. Target organs were segmented using a convolutional neural network (CNN), and novel quantitative imaging biomarkers - SUV percentiles (SUVX%) of 18F-FDG uptake within the target organs - were correlated with the clinical irAE status. Area under the receiver-operating characteristic curve (AUROC) was used to quantify irAE detection performance. Patients who did not experience irAE were used to establish normal ranges for target organ 18F-FDG uptake. Results: A total of 31% (18/58) patients experienced irAE in the three target organs: bowel (n=6), lung (n=5), and thyroid (n=9). Optimal percentiles for identifying irAE were bowel (SUV95%, AUROC=0.79), lung (SUV95%, AUROC=0.98), and thyroid (SUV75%, AUROC=0.88). Optimal cut-offs for irAE detection were bowel (SUV95%>2.7 g/mL), lung (SUV95%>1.7 g/mL), and thyroid (SUV75%>2.1 g/mL). Normal ranges (95% confidence interval) for the SUV percentiles in patients without irAE were bowel [1.74, 2.86 g/mL], lung [0.73, 1.46 g/mL], and thyroid [0.86, 1.99 g/mL]. Conclusions: Increased 18F-FDG uptake within irAE-affected organs provides predictive information about the development of irAE in MM patients receiving ICI and represents a potential quantitative imaging biomarker for irAE. Some irAE can be detected on 18F-FDG PET/CT well before clinical symptoms appear.
Ključne besede: melanoma, malignant melanoma, immune-checkpoint inhibitors, molecular imaging biomarkers
Objavljeno v DiRROS: 07.09.2022; Ogledov: 498; Prenosov: 146
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77. Effect of cluster thinning within the grapevine varietyKatja Šuklje, Anastazija Jež Krebelj, Tanja Vaupotič, Franc Čuš, 2022, izvirni znanstveni članek Ključne besede: grapevine, cluster thinning, Welschriesling, thiols, terpenes, yield, yield parameters, wine parameters
Objavljeno v DiRROS: 06.09.2022; Ogledov: 602; Prenosov: 169
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78. Merjenje tlakov plevralnega prostora med razbremenilno punkcijo (plevralna manometrija) kot varna in objektivna metoda pri ocenjevanju vpliva plevralnega izliva na izražanje simptomovAnita Meglič, Katja Adamič, Vladimir Dimitrić, Vesna Nikolić, Aleš Rozman, Mateja Marc-Malovrh, 2022, izvirni znanstveni članek Povzetek: Izhodišča: Bolniki s plevralnim izlivom pogosto potrebujejo razbremenilno plevralno punkcijo (RPP), po kateri navajajo bolj ali manj izrazito olajšanje dispneje. Zaradi varnosti se priporoča, da se med RPP odstrani do 1.500 mL tekočine. Metode: V raziskavo smo vključili 96 bolnikov, pri katerih je bila potrebna RPP. Zbirali smo ocene stopnje dispneje na lestvici VAS pred, takoj po in 2 uri po RPP, pri 73 bolnikih pa še 24 ur po RPP ter beležili količino odstranjene tekočine. Med RPP smo z vodnim manometrom merili plevralne tlake, iz katerih smo izračunali elastanco plevralnega prostora in na podlagi meritev bolnike razdelili v skupine z različnimi elastančnimi krivuljami. Rezultati: Med začetnim plevralnim tlakom in količino odstranjene tekočine ter olajšanjem dispneje po opravljeni RPP smo ugotovili statistično značilno povezanost. Pri največjem deležu bolnikov smo RPP zaključili zaradi pojava simptomov, zaradi meritev plevralnega tlaka pa smo RPP prekinili pri 16 bolnikih (16,7 %). V skupino z normalno elastančno krivuljo smo uvrstili 74 bolnikov, nezmožnost razpenjanja pljuč pa smo ugotovili pri 22 bolnikih. Med RPP ni bilo pomembnih zapletov, kljub temu da smo več kot 1.500 mL izliva odstranili pri 32 (33 %) bolnikih. Zaključek: Višji začetni plevralni tlak je šibko povezan z višjo začetno stopnjo dispneje in večjim olajšanjem dispneje po opravljeni RPP. Najbolj uporabna je dinamika sprememb plevralnega tlaka, s katero lahko že med RPP prepoznamo nezmožnost razpenjanja pljuč. Med RPP s plevralno manometrijo lahko varno odstranimo tudi več kot 1.500 mL tekočine
Ključne besede: pljuča, dispneja, vizualna analogna lestvica, elastančne krivulje, nezmožnost razpenjanja pljuč
Objavljeno v DiRROS: 29.08.2022; Ogledov: 422; Prenosov: 163
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80. Synoptic risk assessment of groundwater contamination from landfillsSonja Cerar, Luka Serianz, Katja Koren, Joerg Prestor, Nina Mali, 2022, izvirni znanstveni članek Povzetek: Waste management in Europe has improved in recent years, reducing the amount of waste disposed at landfills. However, there are still many landfills in the countries. It is well known that landfills that do not have measures in place to control leachate entering groundwater can contaminate groundwater long after the landfill is closed. Collecting monitoring results from all landfills allows permitting and management agencies to improve action plans. This relies on a synoptic risk assessment that allows prioritization and milestones to be set for required actions. The developed method of synoptic risk assessment is based on a conceptual model of the landfill and the results of chemical groundwater monitoring tested at 69 landfills in Slovenia. The study confirms that most landfills have a direct or indirect impact on groundwater quality. All landfills were classified into three priority classes on the basis of the synoptic risk assessment. The results show that a total of 24 landfills have a clearly pronounced impact on groundwater. A total of 31 landfills have a less pronounced impact due to the favorable natural attenuation capacity of the soil or the technically appropriate design of the landfill itself. A total of 14 landfills have a less pronounced or negligible impact on groundwater.
Ključne besede: conceptual model, synoptic risk assessment, landfill, groundwater, chemical analysis
Objavljeno v DiRROS: 19.07.2022; Ogledov: 554; Prenosov: 291
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