1. Mesenchymal stem cells differentially affect the invasion of distinct glioblastoma cell linesBarbara Breznik, Helena Motaln, Miloš Vittori, Ana Rotter, Tamara Lah Turnšek, 2017, izvirni znanstveni članek Povzetek: Glioblastoma multiforme are an aggressive form of brain tumors that are characterized by distinct invasion of single glioblastoma cells, which infiltrate the brain parenchyma. This appears to be stimulated by the communication between cancer and stromal cells. Mesenchymal stem cells (MSCs) are part of the glioblastoma microenvironment, and their ‘cross-talk’ with glioblastoma cells is still poorly understood. Here, we examined the effects of bone marrow-derived MSCs on two different established glioblastoma cell lines U87 and U373. We focused on mutual effects of direct MSC/glioblastoma contact on cellular invasion in three-dimensional invasion assays in vitro and in a zebrafish embryo model in vivo. This is the first demonstration of glioblastoma cell-type-specific responses to MSCs in direct glioblastoma co-cultures, where MSCs inhibited the invasion of U87 cells and enhanced the invasion of U373. Inversely, direct cross-talk between MSCs and both of glioblastoma cell lines enhanced MSC motility. MSC-enhanced invasion of U373 cells was assisted by overexpression of proteases cathepsin B, calpain1, uPA/uPAR, MMP-2, -9 and -14, and increased activities of some of these proteases, as determined by the effects of their selective inhibitors on invasion. In contrast, these proteases had no effect on U87 cell invasion under MSC co-culturing. Finally, we identified differentially expressed genes, in U87 and U373 cells that could explain different response of these cell lines to MSCs. In conclusion, we demonstrated that MSC/glioblastoma cross-talk is different in the two glioblastoma cell phenotypes, which contributes to tumor heterogeneity.
Ključne besede: glioblastoma multiforme, proteases, mesenchymal stem cells, tumor heterogeneity, zebrafish model
Objavljeno v DiRROS: 24.07.2024; Ogledov: 139; Prenosov: 108
 Celotno besedilo (15,25 MB)
Gradivo ima več datotek! Več... |
2. Lethal and sub-lethal effects and modulation of gene expression induced by T kinase inhibitors in zebrafish (Danio Rerio) embryosTina Eleršek, Matjaž Novak, Mateja Mlinar, Igor Virant, Nika Bahor, Karin Leben, Bojana Žegura, Metka Filipič, 2022, izvirni znanstveni članek Povzetek: Tyrosine kinase inhibitors (TKIs) are designed for targeted cancer therapy. The consumption of these drugs during the last 20 years has been constantly rising. In the zebrafish (Danio rerio) embryo toxicity test, we assessed the toxicity of six TKIs: imatinib mesylate, erlotinib, nilotinib, dasatinib, sorafenib and regorafenib. Imatinib mesylate and dasatinib induced lethal effects, while regorafenib, sorfenib and dasatinib caused a significant increase of sub-lethal effects, predominantly oedema, no blood circulation and formation of blood aggregates. The analyses of the changes in the expression of selected genes associated with the hormone system after the exposure to imatinib mesylate, dasatinib and regorafenib demonstrated that all three tested TKIs deregulated the expression of oestrogen receptor esr1, cytochrome P450 aromatase (cypa19b) and hydroxysteroid-dehydrogenase (hsd3b), regorafenib, and also thyroglobulin (tg). The expression of genes involved in the DNA damage response (gadd45 and mcm6) and apoptosis (bcl2) was deregulated only by exposure to regorafenib. The data indicate that common mechanisms, namely antiangiogenic activity and interference with steroidogenesis are involved in the TKI induced sub-lethal effects and potential hormone disrupting activity, respectively. The residues of TKIs may represent an environmental hazard; therefore, further ecotoxicological studies focusing also on the effects of their mixtures are warranted.
Ključne besede: aquatic toxicity, tyrosine kinase inhibitors, zebrafish embryo toxicity test, gene expression, environmental hazard
Objavljeno v DiRROS: 16.07.2024; Ogledov: 149; Prenosov: 109
Celotno besedilo (9,13 MB)
Gradivo ima več datotek! Več... |
3. Adverse toxic effects of tyrosine kinase inhibitors on non-target zebrafish liver (ZFL) cellsKatja Kološa, Bojana Žegura, Martina Štampar, Metka Filipič, Matjaž Novak, 2023, izvirni znanstveni članek Ključne besede: zebrafish liver cells, ZFL, tyrosine kinase inhibitors, cytotoxicity, cell cycle, genotoxicity, environmental hazard
Objavljeno v DiRROS: 12.07.2024; Ogledov: 303; Prenosov: 130
Celotno besedilo (3,30 MB)
Gradivo ima več datotek! Več... |
4. The hazard assessment of nanostructured CeO [sub] 2-based mixed oxides on the zebrafish Danio rerio under environmentally relevant UV-A exposureAnita Jemec Kokalj, Petar Djinović, Ilja Gasan Osojnik Črnivec, Albin Pintar, 2015, izvirni znanstveni članek Povzetek: The effect of nanomaterials on biota under realistic environmental conditions is an important question. However, there is still a lack of knowledge on how different illumination conditions alter the toxicity of some photocatalytic nanomaterials. We have investigated how environmentally relevant UV-A exposure (intensity 8.50 ± 0.61 W/m2, exposure dose 9.0 J/cm2) affected the toxicity of cerium oxide (CeO2)-based nanostructured materials to the early-life stages of zebrafish Danio rerio. Pure cerium oxide (CeO2), copper–cerium (CuO–CeO2) (with a nominal 10, 15 and 20 mol.% CuO content), cerium–zirconium (CeO2–ZrO2) and nickel and cobalt (Ni–Co) deposited over CeO2–ZrO2 were tested. It was found that under both illumination regimes, none of the tested materials affected the normal development or induced mortality of zebrafish early-life stages up to 100 mg/L. Only in the case of CuO–CeO2, the growth of larvae was decreased (96 h LOEC values for CuCe10, CuCe15 and CuCe20 were 50, 50 and 10 mg/L, respectively). To conclude, CeO2-based nanostructured materials are not severely toxic to zebrafish and environmentally relevant UV-A exposure does not enhance their toxicity.
Ključne besede: Nickel cobalt nanocrystalline catalysts, UV-A phototoxicity, UV-shielding, zebrafish
Objavljeno v DiRROS: 16.12.2014; Ogledov: 9371; Prenosov: 684
 Povezava na celotno besedilo |
