The results of this study showed that anticancer drugs with different mechanisms of chemotherapeutic action exert different genotoxic potential in the test system with human hepatoma HepG2 cells. 5-FU, CDDP and ET induced DNA double strand breaks (DSBs) and showed a pattern of the changes in the expression of DNA damage, apoptosis and proto-oncogenes that is typical for genotoxic compounds. IM only slightly induced formation of DSBs and had no effect on the expression of selected genes, showing different mechanism of action that most probably does not involve direct interaction with DNA. Genotoxic effects of the tested anti-cancer drugs were observed at their therapeutic concentrations that may consequently lead to increased risk for development of delayed adverse effects such as cancer, reproductive effects and heritable disease in patients, with 5-FU, CDDP and ET representing higher hazard than IM.
COBISS.SI-ID: 3595343
In this two generation study with zebrafish (Danio rerio) we showed that exposure to 5-Fluorouracil (5FU), which is one of the most extensively used antineoplastic drugs in cancer therapy, induced histopathological changes in liver and kidney, DNA damage, micronuclei formation and up regulation of several DNAdamage responsive genes and oncogenes (i.e., jun, myca) at concentrations relevant for environmental contamination. Although this chronic exposure to environmentally relevant concentrations of 5FU did not affect the reproduction of the exposed zebrafish, it cannot be excluded that 5FU can lead to degenerative changes, including cancers, which over longterm exposure of several generations might affect fish populations
COBISS.SI-ID: 3417935
The aim of this study was to conduct a comparative in vitro toxicological characterisation of three commonly used cytostatics with different mechanisms of chemotherapeutic action (5-fluorouracil [5-FU], cisplatin [CDDP] and etoposide [ET]) towards zebrafish liver (ZFL) cell line, humanhepatoma (HepG2) cells and human peripheral blood lymphocytes (HPBLs). The highest cytotoxic potential exerted CDDP followed by 5-FU, whereas ET exerted the highest genotoxic potential. ZFL cells were the most susceptible, which raises the question of a negative impact of these pharmaceuticals on fish if discharged into aquatic environments excessively. The high sensitivity of non-target ZFL cells also indicates that these cells could be a good model for testing the genotoxic potential of pharmaceuticals as well as other aquatic pollutants and could serve as an alternative to animal testing in ecotoxicological studies.
COBISS.SI-ID: 3447119
Proteases, including lysosomal cathepsins, are involved in many processes in cancer progression. Only recently, cathepsin K (CatK), originally reported as a collagenolytic protease produced by osteoclasts, appeared to be overexpressed as well in various types of cancers, including brain tumour glioma. In this review, the physiological functions of CatK are presented and compared to its potential role in pathobiolology of processes associated with tumour growth, invasion and metastasis of cancer cells and their interactions with the tumour microenvironment. CatK activity is either indirectly affecting signaling pathways, or directly degrading extracellular matrix (ECM) proteins. In glioma CatK possibly regulates cancer stem-like cell mobilisation out of their niches and modulates recently found physiological CatK substrates, including chemokines and growth factors. Finally, the application of CatK inhibitors, which are already in clinical trials for treatment of osteoporosis, has a potential to attenuate cancer aggressiveness.
COBISS.SI-ID: 3652943
Preverili smo uporabnost U87, U251, in U373 glioblastoma (GBM) celičnih linij kot in vitro modelov za študij učinkov medcelične komunikacije na spremembo njihovega fenotipa v so-kulturi. Bili smo prvi, ki smo opredelili nevralni in mezenhimski molekularni prstni odtis linij U87 in U373. Ob tem smo dokazali, da celice U87 znižajo genomsko stabilnost celic U373 (U251), sicer brez vpliva na njihovo proliferacijo. Obratno pa se ob tem poveča genomska stabilnost celic U87, zniža njihova proliferacija in poveča invazija. V indirektnih in direktnih so-kulturah smo dokazali nasproten učinek celic U87 in U373 druge na drugo v smislu spreminjanja rezistence celic na temozolomid. Z definiranje sprememb izražanja genov med različnimi celicami GBM, smo zagotovili boljše razumevanje mehanizmov v heterogenem glioblastomu, kar predstavlja osnovo za boljšo izvedbo zdravljenja glioma v prihodnosti.
COBISS.SI-ID: 3643471