Mixture toxicity, including agonistic and antagonistic effects, is an unrevealed environmental problem. Estrogenic endocrine disruptors are known to cause adverse effects for aquatic biota, but causative chemicals and their contributions to the total activity in sewage sludge remain unknown. Therefore, advanced analytical methods, a yeast bioassay and mixture toxicity models were concurrently applied for the characterization of 8 selected sludges with delectable estrogenic activity (and 3 sludges with no activity as blanks) out of 25 samples from wastewater treatment plants (WWTPs). The first applied full logistic model adequately explained total activity by considering the concentrations of the monitored compounds. The results showed that the activity was primarily caused by natural estrogens in municipal WWTP sludge. Nevertheless, activity in a sample originating from a car-wash facility was dominantly caused by partial agonists - nonylphenols - and only a model enabling prediction of all dose-response curve parameters of the final mixture curve explained these results. Antiestrogenic effects were negligible, and effect-directed analysis identified the causative chemicals.
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
Neuroblastoma (NBL) originates from undifferentiated cells of the sympathetic nervous system. Chemotherapy is judged to be suitable for successful treatment of this disease. Here, the influence of histone deacetylase (HDAC) inhibitor valproate (VPA) combined with DNA-damaging chemotherapeutic, ellipticine, on UKF-NB-4 and SH-SY5Y neuroblastoma cells was investigated. Treatment of these cells with ellipticine in combination with VPA led to the synergism of their anticancer efficacy. The effect is more pronounced in the UKF-NB-4 cell line, the line with N-myc amplification, than in SH-SY5Y cells. This was associated with caspase-3-dependent induction of apoptosis in UKF-NB-4 cells. The increase in cytotoxicity of ellipticine in UKF-NB-4 by VPA is dictated by the sequence of drug administration; the increased cytotoxicity was seen only after either simultaneous exposure to these drugs or after pretreatment of cells with ellipticine before their treatment with VPA. The synergism of treatment of cells with VPA and ellipticine seems to be connected with increased acetylation of histones H3 and H4. Further, co-treatment of cells with ellipticine and VPA increased the formation of ellipticine-derived DNA adducts, which indicates an easier accessibility of ellipticine to DNA in cells by its co-treatment with VPA and also resulted in higher ellipticine cytotoxicity. The results are promising for in vivo studies and perhaps later for clinical studies of combined treatment of children suffering from high-risk NBL.
- MeSH
- apoptóza MeSH
- elipticiny toxicita MeSH
- inhibitory histondeacetylas toxicita MeSH
- kyselina valproová toxicita MeSH
- lidé MeSH
- mutageny toxicita MeSH
- nádorové buněčné linie MeSH
- neuroblastom metabolismus MeSH
- neurony účinky léků metabolismus MeSH
- synergismus léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Klíčová slova
- bezmléčná dieta, školní stravování,
- MeSH
- dietoterapie * metody MeSH
- dítě MeSH
- fyziologie výživy dětí MeSH
- jídelníček MeSH
- lidé MeSH
- mléčné výrobky škodlivé účinky MeSH
- mléko škodlivé účinky MeSH
- předškolní dítě MeSH
- školy MeSH
- stravovací služby * MeSH
- vitamin D MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- předškolní dítě MeSH
- MeSH
- fyziologie výživy MeSH
- programy Healthy People MeSH
- výchova a vzdělávání MeSH
- zdravý životní styl * MeSH
- Publikační typ
- zprávy MeSH
- Publikační typ
- abstrakt z konference MeSH
Nanoparticles as drug delivery vehicles pose an exciting and promising future for cancer treatment, and offer particular benefits not only for cancer treatment, but also for overcoming of multidrug resistance in cancer tissues. Targeted delivery of anti-neoplastic drugs by nanoparticles promises enhanced drug efficacy, selectivity and reduced systemic toxicity. Nanoparticle systems have unique properties that allow for both passive and active targeting of tumors. Active targeting of nanoparticles, that usually involve surface proteins known to be upregulated in cancer cells, increases accumulation in a tumor. Targeting molecules include antibodies or their fragments, aptamers, or small molecules. This review describes a comprehensive overview of different targeting of nanodrugs.
- MeSH
- antitumorózní látky farmakologie terapeutické užití MeSH
- lidé MeSH
- nádory * farmakoterapie MeSH
- nanočástice * MeSH
- nosiče léků * farmakologie chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
