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EN
High-resolution continuum source atomic absorption spectroscopy (HR-CS AAS) is a valuable analytical technique for metal quantification because of its high sensitivity and selectivity for metal atoms as well as its improved background correction mode. However, the quantification of metals in biological materials, e.g. cell lysates, is still challenging because of matrix effects and other experimental complications. A method to quantify the titanium content of tumor cells exposed to titanium-based drugs was developed using HR-CS AAS. This method allows the quantification of titanium in cell suspensions in the low µg L-1 range with a detection limit of 48.8 µg L-1. The procedure was applied to the study of the cellular uptake of novel titanium metallodrugs (namely titanium (IV) salan complexes) and results showed a higher accumulation of these complexes in cancer cells compared to the titanium lead compound, titanocene dichloride. The improved cellular uptake of the studied complexes indicates a target located inside the cells and this could possibly lead to a higher antitumor effect of this novel class of metallodrugs. The antiproliferative potential of the complexes was confirmed in two different cancer cell lines, in which the titanium complexes showed good to moderate activity.
EN
STI571 (imatinib mesylate; Gleevec®) is an inhibitor that targets the tyrosine kinase activity of Bcr-Abl present in chronic myelogenous leukemia (CML) cells. Some preclinical studies have demonstrated that the combination of STI571 with chemotherapeutic drugs results in enhanced toxicity in Bcr-Abl-positive leukemias. We investigated the potential benefit of using STI571 to down-regulate Bcr-Abl activity for the enhancement of doxorubicin anti-proliferative action in K562 cell line derived from blast crisis of CML. At low concentrations of both drugs (40 nM doxorubicin combined with STI571 in the range of 100-150 nM), the antiproliferative effects were mainly due to cellular differentiation as assessed by benzidine staining for hemoglobin synthesis level and real-time PCR for γ-globin expression. Higher concentrations of STI571 used in combinations with doxorubicin caused mainly apoptosis as shown by DNA degradation and nuclear fragmentation visualized by fluorescence microscopy after DAPI staining, changes in cell morphology observed after Giemza-May Grünwald staining and cellular membrane organization estimated by flow cytometry after Annexin V staining. As compared with either drug alone, cotreatment with STI571 and DOX induced stronger cellular responses. A low concentration of STI571 in combination with a low concentration of DOX might be tested as an alternative approach to increasing the efficacy of chemotherapy against CML.
EN
Neutron activation analysis of the Pleurotus ostreatus showed that adding of solid solution of ZrO2-Y2O3 hydroxide and oxide (3 mol % Y2O3) nanoparticles of size 4 and 9 nm at a concentration of 0.2 weight percent in a nutrient medium (Czapek) alters the character of physiological processes in the biological tissues of the mushrooms. This is manifested in the form of a significant change in morphological and physiological characteristics of the mushrooms and the elemental composition of the dry biomass. In particular, it is shown that the intercalation of nanoparticles into the tissues of the mushrooms leads to an increase of 1.3-1.4 times (more than 2.6 g/dm3) of biomass accumulation (industrial strain HK 35) and decrease of 1.7-1.8 times (below 1.7-2.5 mg/mm3) of concentrations of extracellular proteins into the culture fluid at a substantially constant value of the acidity. It is shown that the addition of ZrO2+3 mol % Y2O3 nanoparticles of sizes 4 or 9 nm into tissue of mushroom at step of the mother mycelium in very small concentrations can alter effectively the chemical composition of the substances produced by the cells and consequently, its physiological activity. It is shown that the use of low concentrations of ZrO2 nanoparticles allow to increase the yield and resistance of crops to diseases up to 1.2-1.5 times, as well as in the long term can be used in biomedical technologies for the treatment of cancer diseases.
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