1. Synthetic cannabinoid WIN 55,212–2 inhibits growth and induces cell death of oral and pancreatic stem-like/poorly differentiated tumor cellsMeng-Wei Ko, Barbara Breznik, Emanuela Senjor, Anahid Jewett, 2022, izvirni znanstveni članek Povzetek: We report here that synthetic cannabinoid WIN 55,212–2 inhibits tumor cell proliferation and induces cell death of oral and pancreatic tumor cells, and the effect is much more pronounced on stem-like/poorly differentiated OSCSCs and MP2 cells when compared to well-differentiated OSCCs, and PL-12 tumor cells. In addition, WIN 55,212-2 decreases cell surface expression of CD44, CD54, MHC class I and PD-L1 on oral and pancreatic tumor cells with the exception of PD-L1 expression on well-differentiated PL-12 pancreatic tumor cells which exhibits an increase in the expression rather than a decrease. Overall, we demonstrate that WIN 55,212-2 has an increased targeting activity against cancer stem cells/poorly differentiated oral and pancreatic tumor cells when compared to well-differentiated tumor cells, and furthermore, such differences in function do not correlate with the levels of CB1 and CB2 receptor expression on tumor cells, suggesting it's function either through post-receptor mediated activation and/or yet-to-be identified novel receptors. Intraperitoneal (IP) delivery of WIN 55-212-2 in humanized BLT mice is found to impart an activating potential for NK cells demonstrating increased NK cell mediated cytotoxicity and secretion of IFN-γ in our preliminary experiments. These results not only suggest a direct targeting of CSCs/poorly differentiated tumors by WIN 55-212-2 but also by indirect targeting of such tumors through the activation and increased functions of NK cells.
Ključne besede: cancer stem cells, cannabinoids, cell death, cancer biology, genetic toxicology
Objavljeno v DiRROS: 17.07.2024; Ogledov: 10; Prenosov: 3
 Celotno besedilo (8,37 MB)
Gradivo ima več datotek! Več... |
2. Infiltrating natural killer cells bind, lyse and increase chemotherapy efficacy in glioblastoma stem-like tumorospheresBarbara Breznik, Meng-Wei Ko, Christopher Tse, Po-Chun Chen, Emanuela Senjor, Bernarda Majc, Anamarija Habič, Nicolas Angelillis, Metka Novak, Vera Župunski, Jernej Mlakar, David Nathanson, Anahid Jewett, 2022, izvirni znanstveni članek Povzetek: Glioblastomas remain the most lethal primary brain tumors. Natural killer (NK) cell-based therapy is a promising immunotherapeutic strategy in the treatment of glioblastomas, since these cells can select and lyse therapy-resistant glioblastoma stem-like cells (GSLCs). Immunotherapy with super-charged NK cells has a potential as antitumor approach since we found their efficiency to kill patient-derived GSLCs in 2D and 3D models, potentially reversing the immunosuppression also seen in the patients. In addition to their potent cytotoxicity, NK cells secrete IFN-γ, upregulate GSLC surface expression of CD54 and MHC class I and increase sensitivity of GSLCs to chemotherapeutic drugs. Moreover, NK cell localization in peri-vascular regions in glioblastoma tissues and their close contact with GSLCs in tumorospheres suggests their ability to infiltrate glioblastoma tumors and target GSLCs. Due to GSLC heterogeneity and plasticity in regards to their stage of differentiation personalized immunotherapeutic strategies should be designed to effectively target glioblastomas.
Ključne besede: glioblastoma, natural killer cells, translational oncology
Objavljeno v DiRROS: 16.07.2024; Ogledov: 17; Prenosov: 2
Celotno besedilo (10,81 MB)
Gradivo ima več datotek! Več... |
3. Upregulation of cathepsin X in glioblastoma : interplay with γ-enolase and the effects of selective cathepsin X inhibitorsBernarda Majc, Anamarija Habič, Metka Novak, Ana Rotter, Andrej Porčnik, Jernej Mlakar, Vera Župunski, Urša Pečar Fonović, Damijan Knez, Nace Zidar, Stanislav Gobec, Janko Kos, Tamara Lah Turnšek, Anja Pišlar, Barbara Breznik, 2022, izvirni znanstveni članek Ključne besede: glioblastoma, cathepsin X, γ-enolase, tumor microenvironment, glioblastoma stem cells, cathepsin X inhibitors
Objavljeno v DiRROS: 16.07.2024; Ogledov: 11; Prenosov: 4
Celotno besedilo (3,51 MB)
Gradivo ima več datotek! Več... |
4. Anti-vimentin nanobody decreases glioblastoma cell invasion in vitro and in vivoAlja Zottel, Metka Novak, Neja Šamec, Bernarda Majc, Sara Colja, Mojca Katrašnik, Miloš Vittori, Barbara Hrastar, Ana Rotter, Andrej Porčnik, Tamara Lah Turnšek, Radovan Komel, Barbara Breznik, Ivana Jovchevska, 2023, izvirni znanstveni članek Povzetek: Purpose: Glioblastoma (GBM) is the most common primary brain tumour and one of the deadliest cancers. In addition to late diagnosis and inadequate treatment, the extremely low survival rate is also due to the lack of appropriate therapeutic biomarkers and corresponding therapeutic agents. One of the potential therapeutic biomarkers is the intermediate filament vimentin, which is associated with epithelial-mesenchymal transition (EMT). The purpose of this study was to analyse the effect of the anti-vimentin nanobody Nb79 on cell invasion in vitro and in vivo. To further our understanding of the mechanism of action, we investigated the association between Nb79 and EMT in GBM and GBM stem cells by analysing the expression levels of key EMT-related proteins. Methods: The expression of vimentin in glioma tissues and cells was determined by RT-qPCR. An invasion assay was performed on differentiated glioblastoma cell line U-87 MG and stem cell line NCH421k in vitro as well as in vivo in zebrafish embryos. The effect of Nb79 on expression of EMT biomarkers beta-catenin, vimentin, ZEB-1 and ZO1 was determined by Western blot and immunocytochemistry. Results: Our study shows that vimentin is upregulated in glioblastoma tissue compared to lower grade glioma and non-tumour brain tissue. We demonstrated that treatment with Nb79 reduced glioblastoma cell invasion by up to 64% in vitro and up to 21% in vivo. In addition, we found that the tight junction protein ZO-1 had higher expression on the cell membrane, when treated with inhibitory anti-vimentin Nb79 compared to control. Conclusion: In conclusion, our results suggest that anti-vimentin nanobody Nb79 is a promising tool to target glioblastoma cell invasion.
Ključne besede: glioblastoma, vimentin, nanobody
Objavljeno v DiRROS: 12.07.2024; Ogledov: 52; Prenosov: 27
Celotno besedilo (2,43 MB)
Gradivo ima več datotek! Več... |
5. New insights in ATP synthesis as therapeutic target in cancer and angiogenic ocular diseasesCornelis J. F. van Noorden, Bahar Yetkin-Arik, Paola Serrano Martinez, Noëlle Bakker, Mathilda E. van Breest Smallenburg, Reinier O. Schlingemann, Ingeborg Klaassen, Bernarda Majc, Anamarija Habič, Urban Bogataj, Katrin S. Galun, Miloš Vittori, Mateja Erdani-Kreft, Metka Novak, Barbara Breznik, Vashendriya V. V. Hira, 2024, pregledni znanstveni članek Povzetek: Lactate and ATP formation by aerobic glycolysis, the Warburg effect, is considered a hallmark of cancer. During angiogenesis in non-cancerous tissue, proliferating stalk endothelial cells (ECs) also produce lactate and ATP by aerobic glycolysis. In fact, all proliferating cells, both non-cancer and cancer cells, need lactate for the biosynthesis of building blocks for cell growth and tissue expansion. Moreover, both non-proliferating cancer stem cells in tumors and leader tip ECs during angiogenesis rely on glycolysis for pyruvate production, which is used for ATP synthesis in mitochondria through oxidative phosphorylation (OXPHOS). Therefore, aerobic glycolysis is not a specific hallmark of cancer but rather a hallmark of proliferating cells and limits its utility in cancer therapy. However, local treatment of angiogenic eye conditions with inhibitors of glycolysis may be a safe therapeutic option that warrants experimental investigation. Most types of cells in the eye such as photoreceptors and pericytes use OXPHOS for ATP production, whereas proliferating angiogenic stalk ECs rely on glycolysis for lactate and ATP production.
Ključne besede: aerobic glycolysis, anaerobic glycolysis, angiogenesis, ATP synthesis, cancer cells, cancer stem cells, endothelial cells, energy metabolism, eye diseases, oxidative phosphorylation, pericytes, retina, Warburg effect
Objavljeno v DiRROS: 18.06.2024; Ogledov: 127; Prenosov: 77
Celotno besedilo (3,75 MB)
Gradivo ima več datotek! Več... |
6. Localization patterns of cathepsins K and X and their predictive value in glioblastomaBarbara Breznik, Clara Limbaeck Stanic, Andrej Porčnik, Andrej Blejec, Miha Koprivnikar Krajnc, Roman Bošnjak, Janko Kos, Cornelis J. F. van Noorden, Tamara Lah Turnšek, 2018, izvirni znanstveni članek Ključne besede: cathepsins, glioblastoma, immunohistochemistry, patient survival, cancer stem cell niches
Objavljeno v DiRROS: 11.06.2024; Ogledov: 83; Prenosov: 26
Celotno besedilo (1,91 MB) |
7. Imaging of human glioblastoma cells and their interactions with mesenchymal stem cells in the zebrafish (Danio rerio) embryonic brainMiloš Vittori, Barbara Breznik, Tajda Gredar, Katja Hrovat, Lilijana Bizjak-Mali, Tamara Lah Turnšek, 2016, izvirni znanstveni članek Ključne besede: brain tumors, tumor microenvironment, animal models, xenotransplantation
Objavljeno v DiRROS: 09.05.2024; Ogledov: 185; Prenosov: 448
Celotno besedilo (1,35 MB) |
8. Organoidi glioblastoma razkrivajo odpornost na standardno terapijoBernarda Majc, Anamarija Habič, Marta Malavolta, Aleksander Sadikov, Andrej Porčnik, Jernej Mlakar, Tamara Lah Turnšek, Barbara Breznik, Metka Novak, 2023, objavljeni povzetek znanstvenega prispevka na konferenci Ključne besede: glioblastom, organoidi, standardna terapija, model ex vivo, biologija raka
Objavljeno v DiRROS: 16.06.2023; Ogledov: 496; Prenosov: 190
Celotno besedilo (345,36 KB)
Gradivo ima več datotek! Več... |
9. Organoidi glioblastoma kot model za preučevanje odpornosti na terapijoAnamarija Habič, Bernarda Majc, Andrej Porčnik, Roman Bošnjak, Boštjan Markelc, Maja Čemažar, Tamara Lah Turnšek, Barbara Breznik, Metka Novak, 2022, objavljeni povzetek znanstvenega prispevka na konferenci Ključne besede: glioblastom, organoidi, odpornost, možganski rak, možganski tumor, onkologija
Objavljeno v DiRROS: 16.06.2022; Ogledov: 645; Prenosov: 258
Celotno besedilo (80,32 KB) |
10. Odpornost glioblastoma na radioterapijo : vpliv rakavih matičnih celic in mikroo[ko]lja tumorjaBarbara Breznik, Bernarda Majc, Anamarija Habič, Urška Ušeničnik, Andrej Porčnik, Roman Bošnjak, Jernej Mlakar, Marija Skoblar Vidmar, Tanja Jesenko, Maja Čemažar, Tamara Lah Turnšek, Metka Novak, 2022, objavljeni znanstveni prispevek na konferenci (vabljeno predavanje) Povzetek: Glioblastom je najpogostejši možganski tumor pri odraslih z zelo slabo prognozo preživetja bolnikov. Ta je posledica odpornosti glioblastoma na standardno zdravljenje, ki vključuje radioterapijo in kemoterapijo. Z namenom načrtovanja učinkovitejših pristopov zdravljenja preučujemo biološke mehanizme odpornosti glioblastoma na radioterapijo s poudarkom na mikrookolju tumorja in rakavih matičnih celicah. V predkliničnih raziskavah uporabljamo napredne in personalizirane celične modele, ki posnemajo mikrookolje tumorja v bolnikih in z večjo natančnostjo napovedo odziv bolnika na zdravljenje. Hkrati so takšni modeli pomembni za testiranje novih pristopov za zdravljenje kot je imunoterapija.
Ključne besede: glioblastom, mikrookolje, organoidi, možganski rak, možganski tumor, onkologija
Objavljeno v DiRROS: 16.06.2022; Ogledov: 753; Prenosov: 228
Celotno besedilo (89,78 KB) |
