20.500.12556/DiRROS-20412 Patient-derived tumor organoids mimic treatment-induced DNA damage response in glioblastoma Glioblastoma (GB) is the most common primary malignant brain tumor, characterized by resistance to therapy. Despite aggressive treatment options, GB remains an incurable disease. Invasiveness and heterogeneity are key GB features that cannot be studied in preclinical in vitro models. In this study, we investigated the effects of standard therapy using patient-derived GB organoids (GBOs). GBOs reflect the complexity and heterogeneity of the original tumor tissue. No significant effect on GBO viability or invasion was observed after irradiation and temozolomide treatment. E3 ubiquitin-protein ligase (MDM2), cyclin-dependent kinase inhibitor 1A (CDKN1A), and the serine/threonine kinases ATM and ATR were upregulated at the gene and protein levels after treatment. Our results show that the p53 pathway and DNA-damage response mechanisms were triggered, suggesting that GBOs recapitulate GB therapy resistance. GBOs thus provide a highly efficient platform to assess the specific responses of GB patients to therapy and to further explore therapy resistance. cellular physiology cellular toxicology in vitro toxicology including 3D culture technical aspects of cell biology cancer glioblastom organoidi monoterpeni rak onkologija celična fiziologija celična toksikologija celična biologija toksikologija in vitro true false true Angleški jezik Slovenski jezik Neznano 2024-09-09 18:02:40 2024-09-09 18:02:41 2024-09-14 03:34:42 0000-00-00 00:00:00 2024 0 0 Soavtorji: Anamarija Habič, Marta Malavolta, Miloš Vittori, Andrej Porčnik, Roman Bošnjak, Jernej Mlakar, Alenka Matjašič, Andrej Zupan, Marija Skoblar Vidmar, Tamara Lah Turnšek, Aleksander Sadikov, Barbara Breznik, Metka Novak; Nasl. z nasl. zaslona; Opis vira z dne 27. 8. 2024; str. 1-19 [art. no.] ǂ110604 iss. 9 Sept. 2024 0000-00-00 Zaloznikova Objavljeno apc 0000-00-00 0000-00-00 2024-09-20 576 2589-0042 10.1016/j.isci.2024.110604 205414147 https://doi.org/10.1016/j.isci.2024.110604 1 302d3799-6eb4-11ef-9d3a-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=28722 RAZ_Majc_Bernarda_2024.pdf RAZ_Majc_Bernarda_2024.pdf 1 220C2B909461DA4CB74BE4BD247ADC6C 986d636d1160dffea54109c0fcaf6d0ebf6aa07b21946c8d768f921eded9a8b4 b1eb83a0-7194-11ef-9d3a-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=28736 Nacionalni inštitut za biologijo 0 0 0