21. Non-clinical in vitro evaluation of antibiotic resistance gene-free plasmids encoding human or murine IL-12 intended for first-in-human clinical studyŠpela Kos, Maša Omerzel, Tanja Jesenko, Boštjan Markelc, Urška Kamenšek, Katarina Žnidar, Urška Matkovič, Andrej Renčelj, Gregor Serša, Rosana Hudej, Aneja Tuljak, Matjaž Peterka, Maja Čemažar, 2021, original scientific article Abstract: Interleukin 12 (IL-12) is a key cytokine that mediates antitumor activity of immune cells. To fulfill its clinical potential, the development is focused on localized delivery systems, such as gene electrotransfer, which can provide localized delivery of IL-12 to the tumor microenvironment. Gene electrotransfer of the plasmid encoding human IL-12 is already in clinical trials in USA, demonstrating positive results in the treatment of melanoma patients. To comply with EU regulatory requirements for clinical application, which recommend the use of antibiotic resistance gene-free plasmids, we constructed and developed the production process for the clinical grade quality antibiotic resistance gene-free plasmid encoding human IL-12 (p21-hIL-12-ORT) and its ortholog encoding murine IL-12 (p21-mIL-12-ORT). To demonstrate the suitability of the p21-hIL-12-ORT or p21-mIL-12-ORT plasmid for the first-in-human clinical trial, the biological activity of the expressed transgene, its level of expression and plasmid copy number were determined in vitro in the human squamous cell carcinoma cell line FaDu and the murine colon carcinoma cell line CT26. The results of the non-clinical evaluation in vitro set the basis for further in vivo testing and evaluation of antitumor activity of therapeutic molecules in murine models as well as provide crucial data for further clinical trials of the constructed antibiotic resistance gene-free plasmid in humans.
Keywords: interleukin 12, gene electrotransfer, antibiotic resistance, plasmids
Published in DiRROS: 07.09.2022; Views: 526; Downloads: 306
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22. Diversity across major and candidate genes in European local pig breedsMaria Muñoz, Riccardo Bozzi, Fabián García, Yolanda Núñez, Claudia Geraci, Alessandro Crovetti, Juan M. García Casco, Estefania Alves, Martin Škrlep, Rui Charneca, Marjeta Čandek-Potokar, 2018, original scientific article Keywords: pig, pig breeds, mutations, causal mutations, candidate mutations, genetic structure, pig morphological traits, productive traits, meat quality, reproductive traits, disease resistance traits
Published in DiRROS: 06.09.2022; Views: 465; Downloads: 0 |
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25. Current trends on mechanical, corrosion resistance, and antibacterial properties of metallic materials : editorialMarjetka Conradi, Aleksandra Kocijan, 2022, preface, editorial, afterword Keywords: steel, corrosion resistance, mechanical properties, antibacterial properties
Published in DiRROS: 22.06.2022; Views: 519; Downloads: 140
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26. The effects of topical antibiotics on eradication and acquisition of third-generation cephalosporin and carbapenem-resistant Gram-negative bacteria in ICU patients : ǂa ǂpost hoc analysis from a multicentre cluster-randomized trialNienke L. Plantinga, Bastiaan H. Wittekamp, Christian Brun-Buisson, Marc J. M. Bonten, 2020, original scientific article Abstract: Objectives: The aim was to quantify the effects of selective digestive tract decontamination (SDD) consisting of a mouth paste and gastro-enteral suspension, selective oropharyngeal decontamination with a mouth paste (SOD) and 1-2% chlorhexidine (CHX) mouthwash on eradication and acquisition of carriage of third-generation cephalosporin-resistant Enterobacterales (3GCR-E) and carbapenem-resistant Gram-negative bacteria (CR-GNB) in Intensive Care Unit (ICU) patients. Methods: This was a nested cohort study within a cluster-randomized cross-over trial in six European countries and 13 ICUs with 8665 patients. Eradication and acquisition during ICU stay of 3GCR-E and CRGNB were investigated separately in the rectum and respiratory tract for the three interventions and compared with standard care (SC) using Cox-regression competing events analyses. Results: Adjusted cause specific hazard ratios (CSHR) for eradication of rectal carriage for SDD were 1.76 (95% CI 1.31-2.36) for 3GCR-E and 3.17 (95% CI 1.60-6.29) for CR-GNB compared with SC. For the respiratory tract, adjusted CSHR for eradication of 3GCR-E were 1.47 (0.98-2.20) for SDD and 1.38 (0.92-2.06) for SOD compared with SC, and for eradication of CR-GNB these were 0.77 (0.41-1.45) for SDD and 0.81 (0.44-1.51) for SOD, compared with SC. Adjusted CSHRs for acquisition of rectal carriage during SDD (compared with SC) were 0.51 (0.40-0.64) for 3GCR-E and of 0.56 (0.40-0.78) for CR-GNB. Adjusted CSHRs for acquiring respiratory tract carriage with 3GCR-E compared with SC were 0.38 (0.28-0.50) for SDD and 0.55 (0.42-0.71) for SOD, and for CR-GNB 0.46 (0.33-0.64) during SDD and 0.60 (0.44-0.81) during SOD, respectively. SOD was not associated with eradication or acquisition of 3GCR-E and CR-GNB in the rectum. Conclusions: Among mechanically ventilated ICU patients, SDD was associated with more eradication and less acquisition of 3GCR-E and CR-GNB in the rectum than SC. SDD and SOD were associated with less acquisition of both 3GCR-E and CR-GNB than SC in the respiratory tract.
Keywords: intensive care units -- analysis -- epidemiology, bacterial drug resistance, anti-infective agents -- therapeutic use decontamination, beta-lactamases, Gram-negative bacteria, gastrointestinal tract -- microbiology -- drug therapy, cohort studies, colonization, ESBL, digestive tract
Published in DiRROS: 27.05.2022; Views: 550; Downloads: 212
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28. Effect of heat treatment on the microstructure and performance of high-velocity air-fuel sprayed WC-10Co4Cr coatingsXuedong Zhou, Haijun Liu, Jishi Zhang, Jinsheng Ji, Wensheng Zhao, Zhimin Zhang, Qiang Wang, Yong Xue, 2021, original scientific article Keywords: heat treatment, WC-10Co4Cr coatings, abrasion resistance, corrosion resistance
Published in DiRROS: 06.05.2022; Views: 478; Downloads: 145
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30. The influence of the plasma-nitriding temperature on the microstructure evolution and surface properties of additive-manufactured 18Ni300 maraging steelMatjaž Godec, Francisco Ruiz-Zepeda, Bojan Podgornik, Črtomir Donik, Aleksandra Kocijan, Danijela Anica Skobir Balantič, 2022, original scientific article Keywords: maraging steel, powder bed fusion, plasma nitriding, microstructure, wear resistance, corrosion resistance
Published in DiRROS: 06.05.2022; Views: 606; Downloads: 212
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