1. Urinary catheters : state of the art and future perspectives – a narrative reviewKristijan Skok, Uroš Bele, Špela Pintar, Zdenka Peršin Fratnik, Katja Kuzmič, Matej Bračič, Lidija Fras Zemljič, Uroš Maver, 2025, pregledni znanstveni članek Opis: Catheter associated urinary tract infection (CAUTI) is the most frequent healthcare associated infection, arising from microbial adhesion to catheter surfaces, biofilm development, and the growing problem of antimicrobial resistance. Many publications have addressed CAUTI epidemiology, biofilm biology, or biomaterials for catheters in isolation, yet there is little literature that connects these areas into a coherent translational perspective. This review seeks to fill that gap by combining an overview of biofilm pathophysiology with recent advances in material based innovations for catheter design, including nanostructured and responsive coatings, sensor enabled systems, additive manufacturing, and three dimensional printing. Established approaches such as hydrophilic or antimicrobial impregnated catheters are considered alongside bio inspired surface textures, zwitterionic polymers, and multifunctional hydrogels. Each strategy is evaluated in terms of maturity, clinical applicability, and barriers to translation, with a focus on shifting from antibiotic dependent treatment toward prevention of biofilm formation. By bringing together knowledge from microbiology, engineering, and clinical urology, the review outlines pathways for developing the next generation of catheters that improve outcomes and reduce infection rates.
Ključne besede: urinary catheters, urinary tract infection, antibiotic resistance, nanotechnology, biomedical engineering
Objavljeno v DKUM: 15.09.2025; Ogledov: 0; Prenosov: 1
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2. Tumor-infiltrating lymphocytes in breast and female genital tract cancers : overlooked potential and unexplored frontiersKristijan Skok, Umberto Maccio, Spencer D. Martin, Konstantin Bräutigam, 2025, pregledni znanstveni članek Opis: Background: The growing success of cancer immunotherapies has led to significant advances in oncology. However, despite these promising developments, cancer-related mortality remains high for common cancer types such as breast and lower female genital tract cancers. Method: Here, we synthesize recent findings on the prognostic relevance of tumor-infiltrating lymphocytes (TILs) in breast, endometrial, tubo-ovarian, and vulvar cancer. Our analysis covers the relationship between TIL counts and density, immune cell subtype combinations, immunotherapy approaches, and patient outcomes. Results: High TIL infiltration, especially CD8+ T-cells, generally correlates with improved outcomes such as in endometrial cancer (especially the POLE-ultramutated subgroup), invasive breast cancer, and ovarian epithelial tumors. However, in ductal carcinoma in situ (DCIS) of the breast, elevated TIL counts are linked to a worse prognosis. Ethnicity, the tumor microenvironment (TME), and molecular profiles further complicate the prognostic utility of TILs. Conclusions: TIL-based therapies have shown potential in personalized immunotherapy, particularly in recurrent, refractory ovarian cancer. Limited research on rarer gynecologic tumors hinders broader clinical applications.
Ključne besede: breast cancer, endometrial cancer, fallopian tube, immunotherapy, ovarian cancer, review, tumor microenvironment (TME), tumor‐infiltrating lymphocytes (TILs), vulvar cancer
Objavljeno v DKUM: 18.08.2025; Ogledov: 0; Prenosov: 10
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3. Tumor immune microenvironment in pancreatic ductal adenocarcinoma revisited - Exploring the "Space"Konstantin Bräutigam, Kristijan Skok, Krzysztof Szymonski, Charlotte Vestrup Rift, Eva Karamitopoulou, 2025, pregledni znanstveni članek Opis: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most deadly malignancies with a highly immunosuppressive tumor immune microenvironment (TIME) that hinders effective therapy. PDAC is characterized by significant heterogeneity in immune cell composition, spatial distribution and activation states, which impacts tumor progression and treatment response. Tumour-infiltrating lymphocytes (TILs), including CD4+ T-helper cells, CD8+ cytotoxic T-cells and FOXP3+ regulatory T-cells, play a key role in immune regulation, yet PDAC is largely an immunologically "cold" tumour with limited effector T-cell infiltration. The surrounding cellular microenvironment, particularly Cancer Associated Fibroblasts (CAFs) and macrophages, contributes to immune evasion by promoting a fibrotic and desmoplastic barrier that limits TIL infiltration. The prognostic significance of TILs is increasingly recognized, with higher densities correlating with improved survival, whereas regulatory T-cell infiltration and immunosuppressive stromal interactions are associated with poor outcomes. Emerging therapeutic strategies targeting the TIME (e.g., CAFs), immune checkpoint inhibitors, and TIL-based therapies offer the potential to overcome resistance. Future research must focus on optimizing immunotherapy strategies and unravelling the complex stromal-immune interactions to improve clinical translation.
Ključne besede: immune system, pancreatic adenocarcinoma (PDAC), spatial analysis, tumor immune microenvironment (TIME), tumor infiltrating lymphocytes (TILs)
Objavljeno v DKUM: 18.08.2025; Ogledov: 0; Prenosov: 1
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4. MFUM-BrTNBC-1, a newly established patient-derived triple-negative breast cancer cell line : molecular characterisation, genetic stability, and comprehensive comparison with commercial breast cancer cell linesKristijan Skok, Lidija Gradišnik, Helena Sabina Čelešnik, Marko Milojević, Uroš Potočnik, Gregor Jezernik, Mario Gorenjak, Monika Sobočan, Iztok Takač, Rajko Kavalar, Uroš Maver, 2022, izvirni znanstveni članek Opis: Triple-negative breast cancer (TNBC) is a breast cancer (BC) subtype that accounts for
approximately 15–20% of all BC cases. Cancer cell lines (CLs) provide an efficient way to model the
disease. We have recently isolated a patient-derived triple-negative BC CL MFUM-BrTNBC-1 and
performed a detailed morphological and molecular characterisation and a comprehensive comparison
with three commercial BC CLs (MCF-7, MDA-MB-231, MDA-MB-453). Light and fluorescence
microscopy were used for morphological studies; immunocytochemical staining for hormone receptor,
p53 and Ki67 status; RNA sequencing, qRT-PCR and STR analysis for molecular characterisation; and
biomedical image analysis for comparative phenotypical analysis. The patient tissue-derived MFUMBrTNBC-1 maintained the primary triple-negative receptor status. STR analysis showed a stable and
unique STR profile up to the 6th passage. MFUM-BrTNBC-1 expressed EMT transition markers and
displayed changes in several cancer-related pathways (MAPK, Wnt and PI3K signalling; nucleotide
excision repair; and SWI/SNF chromatin remodelling). Morphologically, MFUM-BrTNBC-1 differed
from the commercial TNBC CL MDA-MB-231. The advantages of MFUM-BrTNBC-1 are its isolation
from a primary tumour, rather than a metastatic site; good growth characteristics; phenotype identical
to primary tissue; complete records of origin; a unique identifier; complete, unique STR profile;
quantifiable morphological properties; and genetic stability up to (at least) the 6th passage.
Ključne besede: hormonal receptors, MFUM-BrTNBC-1, MCF-7, MDA-MB-231, MDA-MB-453
Objavljeno v DKUM: 10.04.2025; Ogledov: 0; Prenosov: 8
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5. Networks behind the morphology and structural design of living systemsMarko Gosak, Marko Milojević, Maja Duh, Kristijan Skok, Matjaž Perc, 2022, pregledni znanstveni članek Opis: Technological advances in imaging techniques and biometric data acquisition have enabled us to apply methods of network science to study the morphology and structural design of organelles, organs, and tissues, as well as the coordinated interactions among them that yield a healthy physiology at the level of whole organisms. We here review research dedicated to these advances, in particular focusing on networks between cells, the topology of multicellular structures, neural interactions, fluid transportation networks, and anatomical networks. The percolation of blood vessels, structural connectivity within the brain, the porous structure of bones, and relations between different anatomical parts of the human body are just some of the examples that we explore in detail. We argue and show that the models, methods, and algorithms developed in the realm of network science are ushering in a new era of network-based inquiry into the morphology and structural design of living systems in the broadest possible terms. We also emphasize that the need and applicability of this research is likely to increase significantly in the years to come due to the rapid progress made in the development of bioartificial substitutes and tissue engineering.
Ključne besede: network, morphology, structural properties, statistical physics
Objavljeno v DKUM: 17.09.2024; Ogledov: 0; Prenosov: 13
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6. Novel methacrylate-based multilayer nanofilms with incorporated FePt-based nanoparticles and the anticancer drug 5-fluorouracil for skin cancer treatmentKristijan Skok, Tanja Zidarič, Kristjan Orthaber, Matevž Pristovnik, Nina Kostevšek, Kristina Žužek Rožman, Sašo Šturm, Lidija Gradišnik, Uroš Maver, Tina Maver, 2022, izvirni znanstveni članek Opis: Despite medical advances, skin-associated disorders continue to pose a unique challenge to physicians worldwide. Skin cancer is one of the most common forms of cancer, with more than one million new cases reported each year. Currently, surgical excision is its primary treatment; however, this can be impractical or even contradictory in certain situations. An interesting potential alternative could lie in topical treatment solutions. The goal of our study was to develop novel multilayer nanofilms consisting of a combination of polyhydroxyethyl methacrylate (PHEMA), polyhydroxypropyl methacrylate (PHPMA), sodium deoxycholate (NaDOC) with incorporated superparamagnetic iron–platinum nanoparticles (FePt NPs), and the potent anticancer drug (5-fluorouracil), for theranostic skin cancer treatment. All multilayer systems were prepared by spin-coating and characterised by atomic force microscopy, infrared spectroscopy, and contact angle measurement. The magnetic properties of the incorporated FePt NPs were evaluated using magnetisation measurement, while their size was determined using transmission electron microscopy (TEM). Drug release performance was tested in vitro, and formulation safety was evaluated on human-skin-derived fibroblasts. Finally, the efficacy for skin cancer treatment was tested on our own basal-cell carcinoma cell line.
Ključne besede: nanomaterials, bimodal therapy, topical skin treatmen, magnetic nanoparticles, thin films, skin cancer, methacrylates
Objavljeno v DKUM: 04.07.2024; Ogledov: 98; Prenosov: 18
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7. Multilayer methacrylate-based wound dressing as a therapeutic tool for targeted pain reliefTanja Zidarič, Kristijan Skok, Kristjan Orthaber, Matevž Pristovnik, Lidija Gradišnik, Tina Maver, Uroš Maver, 2023, izvirni znanstveni članek Opis: This study presents an innovative wound dressing system that offers a highly effective therapeutic solution for treating painful wounds. By incorporating the widely used non-steroidal anti-inflammatory drug diclofenac, we have created an active wound dressing that can provide targeted pain relief with ease. The drug was embedded within a biocompatible matrix composed of polyhydroxyethyl methacrylate and polyhydroxypropyl methacrylate. The multilayer structure of the dressing, which allows for sustained drug release and an exact application, was achieved through the layer-by-layer coating technique and the inclusion of superparamagnetic iron platinum nanoparticles. The multilayered dressings’ physicochemical, structural, and morphological properties were characterised using various methods. The synergistic effect of the incorporated drug molecules and superparamagnetic nanoparticles on the surface roughness and release kinetics resulted in controlled drug release. In addition, the proposed multilayer wound dressings were found to be biocompatible with human skin fibroblasts. Our findings suggest that the developed wound dressing system can contribute to tailored therapeutic strategies for local pain relief.
Ključne besede: wound dressings, pain relief, superparamagnetic nanoparticles, methacrylate
Objavljeno v DKUM: 19.04.2024; Ogledov: 485; Prenosov: 473
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8. First treatment with venovenous extracorporeal membrane oxygenation in MariborKristijan Skok, Andrej Markota, Franc Svenšek, Andreja Sinkovič, 2019, drugi znanstveni članki Ključne besede: zunajtelesni krvni obtok, VV ECMO, refraktarna hipoksemija, akutna dihalna odpoved, intenzivna medicina, enota za intenzivno terapijo
Objavljeno v DKUM: 05.04.2024; Ogledov: 177; Prenosov: 21
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10. Analiza fenotipskih, molekularnih in genetskih lastnosti nove celične linije trojno negativnega raka dojkKristijan Skok, 2022, doktorska disertacija Opis: Rak dojk je najpogostejši rak na svetu. Eden izmed njegovih podtipov je trojno negativni rak dojk (TNRD), za katerega je značilen agresiven potek, slabša prognoza in heterogenost. V svoji doktorski nalogi predstavim novo izolirano celično linijo TNRD, poimenovano MFUM-BrTNBC1. Linija je bila celovito karakterizirana (morfološko, fenotipsko, genotipsko). Za kontrole so služile komercialne celične linije z različnimi receptorskimi profili (MCF-7, MDA-MB-231, MDA-MB-453). Primerjalne morfološke analize so bile opravljene s pomočjo mikroskopije ter biomedicinske slikovne analize. S pomočjo imunocito/histokemičnih barvanj je bila preverjena izraženost hormonskih receptorjev (estrogen, progesteron), HER2, p53 in Ki-67 statusa. Ekspresija receptorjev je bila dodatno preverjena na transkripcijski ravni s qRT-PCR metodo. Dodatno je bilo opravljeno RNA sekvenciranje za molekularno analizo. Avtentičnost celičnih linij je bila preverjena s pomočjo STR profiliranja. MFUM-BrTNBC-1 celična linija je ohranila trojno negativni receptorski status in genetsko stabilnost do vsaj 6. pasaže. Rezultati STR analize in navzkrižna preverba z mednarodnimi bazami so dokazali avtentičnost celične linije. MFUM-BrTNBC1 se je po morfologiji celic razlikovala tudi od TNRD celične linije MDA-MB-231. Razlike od komercialne linije, predstavljajo tudi glavne prednostne lasnosti MFUM-BrTNBC-1. Te so izolacija iz primarnega tumorskega tkiva, popoln izvorni zapis, mednarodno poimenovanje, celoten in edinstven STR profil ter genetska stabilnost do vsaj 6. pasaže.
Ključne besede: trojno negativni rak dojk, MFUM-BrTNBC-1, rak dojk, in-vitro modeli, celične linije
Objavljeno v DKUM: 29.11.2022; Ogledov: 823; Prenosov: 81
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