1. 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, original scientific article Abstract: 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.
Keywords: glioblastoma, vimentin, nanobody
Published in DiRROS: 12.07.2024; Views: 6; Downloads: 3
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2. 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, review article Abstract: 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.
Keywords: aerobic glycolysis, anaerobic glycolysis, angiogenesis, ATP synthesis, cancer cells, cancer stem cells, endothelial cells, energy metabolism, eye diseases, oxidative phosphorylation, pericytes, retina, Warburg effect
Published in DiRROS: 18.06.2024; Views: 119; Downloads: 73
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3. 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, published scientific conference contribution abstract Keywords: glioblastom, organoidi, standardna terapija, model ex vivo, biologija raka
Published in DiRROS: 16.06.2023; Views: 496; Downloads: 187
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4. 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, published scientific conference contribution abstract Keywords: glioblastom, organoidi, odpornost, možganski rak, možganski tumor, onkologija
Published in DiRROS: 16.06.2022; Views: 640; Downloads: 255
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5. 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, published scientific conference contribution (invited lecture) Abstract: 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.
Keywords: glioblastom, mikrookolje, organoidi, možganski rak, možganski tumor, onkologija
Published in DiRROS: 16.06.2022; Views: 737; Downloads: 227
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