1. Posamezne komponente vejpa zmanjšajo živost jetrnih, pljučnih in možganskih celicPia Žižek, Monika Minjovič, Špela Rozman, Vito Ham, Barbara Breznik Vittori, Metka Novak, Martina Štampar, 2026, izvirni znanstveni članek Povzetek: Uporaba vejpov, na videz neškodljive alternative klasičnih cigaret, narašča, zlasti med mladimi. Njihove privlačne arome in izstopajoče barvite embalaže pomembno prispevajo k njihovi priljubljenosti. Zaradi pomanjkljivih podatkov o njihovi škodljivosti in vplivu na zdravje smo želeli ovrednotiti vpliv sedmih izbranih vejpov in njihovih posameznih komponent, kot so arome, nikotin in topila, na morfologijo in živost humanih jetrnih, pljučnih in možganskih celic in vitro. Vejpi in njihove komponente so pomembno vplivale na morfologijo celic, predvsem so povzročile njihovo krčenje in prekinjanje medceličnih povezav. Ugotovili smo, da vejpi povzročijo od koncentracije odvisno citotoksičnost; pri nizkih koncentracijah večina ni povzročila statistično pomembnih razlik, najvišja koncentracija pa je pri večini vejpov povzročila upad živosti celic. Posamezne komponente so povzročile večji upad živosti celic v primerjavi s celotnimi vejpi. Najizrazitejši učinek so imele arome. Izsledki naših raziskav nakazujejo na akutne toksične učinke vejpov in njihovih komponent. Zaradi kratkotrajne prisotnosti vejpov na trgu pa je še nemogoče zanesljivo oceniti njihove dolgoročne učinke na zdravje ljudi.
Ključne besede: arome, citotoksičnost, humani modeli celic, vejp
Objavljeno v DiRROS: 28.08.2026; Ogledov: 141; Prenosov: 47
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2. Trametinib-mediated MEK inhibition impairs cancer cell viability and invasion in patient-derived tumor avatars of glioblastoma with extraneural metastases : a proof-of-concept studyMetka Novak, Bernarda Majc, Marija Skoblar Vidmar, Špela Kladnik, Tina Kolenc Milavec, Anamarija Habič, Simona Katrin Galun, Pia Žižek, Andrej Porčnik, Alenka Matjašič, Andrej Zupan, Miha Jerala, Matic Bošnjak, Borut Prestor, Barbara Breznik Vittori, 2026, izvirni znanstveni članek Povzetek: Glioblastoma (GBM) remains one of the most lethal human malignancies, yet extraneural metastases are exceptionally rare and poorly understood. Standard treatment—surgical resection followed by chemoradiotherapy—offers only modest survival benefits, and therapeutic options for metastatic GBM are limited. Here, we describe a rare clinical case of metastatic GBM and provide comprehensive molecular characterization alongside a potential targeted treatment strategy. The tumor exhibited several molecular features associated with aggressive behavior, including alterations in the tumor suppressor genes NF1, TP53, PTEN, and RB1, a mesenchymal DNA‑methylation subclass, and activation of the MAPK signaling pathway. To functionally evaluate therapeutic vulnerabilities, we developed tumor models using patient‑derived GBM cells and their assembloids with cerebral organoids that recapitulate patient‑specific tumor biology and the human brain microenvironment. We identified the MEK inhibitor trametinib as a promising candidate capable of selectively reducing viability and invasion of highly aggressive, stem‑like GBM cells within our personalized patient-derived tumor avatars. This work highlights the proof-of-concept evidence that MEK pathway inhibition may represent a potential therapeutic vulnerability to counteract rapid tumor spread and improve responsiveness to temzolomide in this individual metastatic GBM case. Study underscores the need for continued research to advance targeted, multi‑modal therapeutic approaches for GBM.
Ključne besede: glioblastoma, extraneural metastasis, rare clinical case, organoids, MEK inhibitor, cancer stem cells, cell invasion
Objavljeno v DiRROS: 12.08.2026; Ogledov: 232; Prenosov: 135
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3. Načrt ravnanja z raziskovalnimi podatki projekta J7-70250 : iskanje novih bioloških označevalcev za izboljšano zdravljenje glioblastoma: lov na invazivne rakave celice : verzija dokumenta 1.02026, druge monografije in druga zaključena dela Ključne besede: možganski tumor, glioblastom, biološki označevalci, biobanka, odpornost na zdravljenje, prognoza, slikanje z magnetno resonanco, umetna
inteligenca, heterogenost, matične celice, tumorsko mikrookolje, sistem za podporo kliničnemu odločanju
Objavljeno v DiRROS: 21.07.2026; Ogledov: 358; Prenosov: 89
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4. Invasive properties of patient-derived glioblastoma cells after reversible electroporation in vitroAnja Blažič, Bernarda Majc, Metka Novak, Barbara Breznik Vittori, Lea Rems, 2025, izvirni znanstveni članek Povzetek: Background. Electroporation-based therapies are being explored in glioblastoma (GB) treatment, as means of enhancing drug delivery or achieving nonthermal ablation. Yet, little is known about how sublethal exposure affects the invasive behaviour of GB tumour cells. Materials and methods. Five patient-derived GB cell lines were initially screened for intrinsic invasive potential, and two most invasive (NIB140 CORE and NIB216 CORE) were selected for further experiments with electroporation treatment. Cells in suspension were exposed to bursts of high-frequency biphasic electric pulses resulting in electric field strength of 1 kV/cm, which corresponded to conditions of reversible electroporation. Changes in cell invasion and gene regulation were assessed 24 hours after electroporation using transwell assay and RNA transcriptome analysis, respectively. Results. Reversible electroporation at 1.0 kV/cm enhanced invasion in a cell line-dependent manner. NIB140 CORE showed a consistent and pronounced increase, with a median of 3.74-fold (274%) higher number of invading cells compared to sham control. In contrast, NIB216 CORE exhibited only a modest increase in invasion (1.30-fold; 30%). Transcriptomic profiling identified modulation of genes linked to extracellular matrix organization and ion channel activity in NIB140 CORE, and cytoskeletal remodelling in NIB216 CORE, indicating the activation of invasion-related pathways. Conclusions. These findings highlight a potential risk of pro-invasive responses in GB cells. In tumour ablation with irreversible electroporation, this concern relates to cells in the peripheral zone that may experience only sublethal electric fields, while in electrochemotherapy, a similar risk may arise if permeabilized cells are not effectively eliminated due to insufficient local drug delivery. Nevertheless, the two tested cell lines responded differently, underscoring patientspecific heterogeneity and the need for validation in more physiologically relevant models.
Ključne besede: electroporation, high-frequency electric pulses, glioblastoma, patient-derived cells, invasion
Objavljeno v DiRROS: 17.06.2026; Ogledov: 272; Prenosov: 336
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5. Glioblastoma–natural killer cell crosstalk: insights from dynamic spheroid models reveal the importance of secreted cytokines and the CD155 axisAnamarija Habič, Tina Kolenc Milavec, Pia Žižek, Špela Kladnik, Bernarda Majc, Emanuela Senjor, Milica Perišić, Andrej Porčnik, Borut Prestor, Urban Švajger, Metka Novak, Barbara Breznik Vittori, 2026, izvirni znanstveni članek Povzetek: Glioblastoma (GB) is an aggressive primary brain cancer with poor patient prognosis. Natural killer (NK) cells can recognise and eliminate a range of malignant cells, including GB stem cells, which drive GB recurrence. NK cell-based immunotherapy has emerged as a promising approach for GB treatment, but a better understanding of the complex crosstalk between GB and NK cells is needed, particularly within the immunosuppressive GB tumour microenvironment. In this study, we established a reproducible protocol for the production and dynamic culture of uniformly sized GB spheroids using the Celvivo Clinostar system. Our spheroids recapitulated the heterogeneous structure of GB and expressed ligands for NK cell receptors at levels distinct from those observed in corresponding GB cell lines in standard culture, implicating altered sensitivity of GB cells to NK cells in dynamic 3D cultures. GB-NK cell crosstalk was GB cell type dependent and the ability of NK cells to infiltrate GB did not necessarily correlate with their cytotoxicity against GB cells. Spheroids derived from differentiated GB cells secreted higher levels of immunomodulatory cytokines compared to spheroids from GB stem-like cells, and a prominent increase in the secretion of immune-attracting factors was observed in their co-cultures with NK cells. Finally, the CD155-DNAM1/TIGIT axis was indicated as an important regulator of NK cell cytotoxicity against GB stem-like cells. Collectively, our results highlight important factors in GB-NK cell communication and provide a groundwork for further targeted research as well as therapeutic evaluation of NK cell-based approaches in the established dynamic 3D cultures.
Ključne besede: glioblastoma, immunotherapy, dynamic in vitro models, natural killer cells, cytotoxicity, 21 infiltration, cytokines, CD155
Objavljeno v DiRROS: 11.06.2026; Ogledov: 353; Prenosov: 287
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7. Proximity-induced transfer of a mass tag enables direct profiling of active matrix metalloproteasesLomane Berthy, Ugo Pasco, Mylene Sejalon-Cipolla, Metka Novak, Barbara Breznik Vittori, 2026, izvirni znanstveni članek Povzetek: Conventional activity-based probes in activity-based protein profiling (ABPP) require enrichment or reporter tags for detection, which limits sensitivity and multiplexing. Here, we present an enrichment-free chemoproteomic approach that enables direct mass spectrometric detection by Matrix-Assisted Laser Desorption/Ionization (MALDI) of active proteases. An active-site–directed affinity probe transfers, through a proximity-induced reaction, a MALDI-detectable α-cyano-4-hydroxycinnamic acid (CHCA) tag exclusively to catalytically active forms of matrix metalloproteases (MMPs). The CHCA label enhances ionization efficiency and markedly improves signal-to-noise ratios, allowing confident identification of CHCA-labelled peptides under discriminating analytical conditions. Each active metalloprotease is thereby, associated with a distinct set of CHCA signature peptides, defining its activity fingerprint. This workflow achieves multiplexed and quantitative activity profiling of MMPs, directly in complex proteomes. This design expands ABPP into the mass spectrometry domain and establishes a robust platform for activity-based enzyme detection.
Ključne besede: activity-based probes, chemoproteomic, mass tag, proximity-induced labelin
Objavljeno v DiRROS: 05.05.2026; Ogledov: 403; Prenosov: 431
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8. Meroslovna podpora za izboljšanje genomskega profiliranja v diangositki rakaMojca Milavec, Alexandra Bogožalec Košir, Metka Novak, Barbara Breznik Vittori, Carole A. Foy, Carla Divieto, 2025, objavljeni znanstveni prispevek na konferenci Ključne besede: tumorji, genomsko profiliranje, diagnostika raka, GenomeMET
Objavljeno v DiRROS: 11.03.2026; Ogledov: 481; Prenosov: 190
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9. Vrednotenje različnih metod ekstrakcije nukleinskih kislin iz humane celične 3D kulture rakaStefanija Ivanova, Alexandra Bogožalec Košir, Metka Novak, Barbara Breznik Vittori, Mojca Milavec, 2025, objavljeni znanstveni prispevek na konferenci Ključne besede: celične kulture, tumorji, molekularna diagnostika, ekstrakcijske metode, kontrola kakovosti, GenomeMET
Objavljeno v DiRROS: 11.03.2026; Ogledov: 611; Prenosov: 195
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10. MAGEA3/6 tumour antigens regulate glycolytic protein hexokinase to enhance pancreatic cancer cell survival under metabolic stressVesna Jurjevič, Jerneja Koren, Sima Tozandehjani, Sara Uhan, Lara Snoj, Barbara Breznik Vittori, Juan Solano, Klementina Fon Tacer, 2024, objavljeni povzetek znanstvenega prispevka na konferenci Ključne besede: pancreatic cancer, metabolism, MAGE, oncology
Objavljeno v DiRROS: 25.02.2026; Ogledov: 629; Prenosov: 157
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