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| Description
| - Neuroblastoma, a tumor of the peripheral sympathetic nervous system, is the most frequent solid extra cranial tumor in children and is a major cause of death from neoplasia in infancy. Still little improvement in therapeutic options has been made, requiring a need for the development of new therapies. The project addresses still unsettled questions, which of mechanisms of action of DNA-damaging drugs both currently used for treatment of human neuroblastomas (doxorubicin, cis-platin and etoposide) and another anticancer agent decreasing growth of neuroblastomas in vitro, ellipticine, are predominant mechanism(s) responsible for their antitumor action in vitro (neuroblastoma cells) and in vivo (neuroblastoma xenograft tumours). The project will also investigate the effects of hypoxia on efficiencies and mechanisms of actions of these drugs and whether they are capable of inducing chemoresistance in neuroblastomas. Their effects in combination with histone deacetylase inhibitors and mechanisms of such effects in vitro and in vivo are other subjects, which will be studied. Such a study will increase our knowledge to explain the proper function of these drugs on the molecular level, which should be utilized for the development of new therapies for neuroblastomas. (en)
- Neuroblastomy jsou tumory periferního nervového systému patřící mezi obtížně léčitelné tumory dětské populace. Ačkoliv vývoji nových terapií této choroby se věnuje značná pozornost, stále nevede k uspokojivým výsledkům. Cílem projektu je poznání mechanismů působení protinádorových agens na neuroblastomy in vitro (neuroblastomové linie) a in vivo (experimentální modely s lidskými neuroblastomy). Jedná se o protinádorová agens způsobující různá poškození DNA, a to jak běžně užívaná pro léčení (doxorubicin, cis-platina a etoposid), tak i další látku, které snižuje růst neuroblastomových buněčných linií, ellipticinu. Záměrem projektu je rovněž poznání vlivu hypoxie na účinnost těchto léčiv a jejich mechanismus působení, a poznání jejich potenciálu indukovat chemoresistenci v neuroblastomových liniích. Dalším cílem projektu je poznání vlivu těchto léčiv na růst neuroblastomů in vitro a in vivo a mechanismus jejich působení v kombinaci s inhibitory histondeacetylas. Výsledky získané touto studii vysvětlí aktuální mechanismy působení studovaných léčiv na molekulární úrovni a přispějí k návrhu vývoje nových terapeutických postupů v léčbě neuroblastomů.
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| Title
| - Study of contribution of different DNA-damaging mechanisms to toxicity of cytostatics to human chemosensitive and chemoresistant neuroblastomas (en)
- Studie participace specifických mechanismů poškození DNA na cytoxicitě cytostatik vůči lidským chemosensitivním a chemorestentním neuroblastomům
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| skos:notation
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| http://linked.open...avai/cep/aktivita
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| http://linked.open...kovaStatniPodpora
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| http://linked.open...ep/celkoveNaklady
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| http://linked.open...datumDodatniDoRIV
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| http://linked.open...i/cep/druhSouteze
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| http://linked.open...ep/duvernostUdaju
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| http://linked.open.../cep/fazeProjektu
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| http://linked.open...ai/cep/hlavniObor
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| http://linked.open...hodnoceniProjektu
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| http://linked.open...vai/cep/kategorie
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| http://linked.open.../cep/klicovaSlova
| - Cancer neuroblastoma DNA-targeting DNA-damage treatment (en)
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| http://linked.open...ep/partnetrHlavni
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| http://linked.open...inujicichPrijemcu
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| http://linked.open...cep/pocetPrijemcu
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| http://linked.open...ocetSpoluPrijemcu
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| http://linked.open.../pocetVysledkuRIV
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| http://linked.open...enychVysledkuVRIV
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| http://linked.open...lneniVMinulemRoce
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| http://linked.open.../prideleniPodpory
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| http://linked.open...iciPoslednihoRoku
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| http://linked.open...atUdajeProjZameru
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| http://linked.open.../vavai/cep/soutez
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| http://linked.open...usZobrazovaneFaze
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| http://linked.open...ai/cep/typPojektu
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| http://linked.open...ep/ukonceniReseni
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| http://linked.open.../cep/vedlejsiObor
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| http://linked.open...ep/zahajeniReseni
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| http://linked.open...jektu+dodavatelem
| - Hlavním přínosem byly nové poznatky o poškození DNA vybranými cytostatiky na modelu lidských neuroblastomů. Deset stanovených cílů bylo průběžně plněno. Vysoký počet (68) prací s dedikací k projektu v časopisech s nízkým a středním impaktem a rozsáhlá prezentace výsledků špatnou angličtinou v závěrečné zprávě nasvědčují, že projektu by prospěla preference kvality nad kvantitou. (cs)
- New findings about the DNA damage by selected cytostatics represent the main accomplishment of the project. Ten stated goals were achieved in time. High number of papers (68) dedicated to the project in journals with low or medium impact and extensive presentation of results in final report in imperfect English indicate that the project would benefit from preference for quality over quantity. (en)
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| http://linked.open...tniCyklusProjektu
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| is http://linked.open...vavai/riv/projekt
of | - Doxorubicin Encapsulation Investigated by Capillary Electrophoresis with Laser- Induced Fluorescence Detection
- MONITORING OF DNA-DOXORUBICIN INTERACTIONS BY ELECTROCHEMICAL METHODS
- Ellipticines as DNA-Targeted Chemotherapeutics
- Electrochemical Study of Ellipticine Interaction with Single and Double Stranded Oligonucleotides
- A Novel Insight into the Cardiotoxicity of Antineoplastic Drug Doxorubicin
- Electrochemical Determination of Enzymes Metabolizing Ellipticine in Thyroid Cancer Cells - a Tool to Explain the Mechanism of Ellipticine Toxicity to these Cells
- Effect of sarcosine on antioxidant parameters and metallothionein content in the PC-3 prostate cancer cell line
- The effect of benzo[a]pyrene on metabolic activation of anticancer drug ellipticine in mice
- Electrochemical Behaviour of Doxorubicin Encapsulated in Apoferritin
- Interactions of Platinum-Based Cytostatics with Metallothionein Revealed by Electrochemistry
- Photo-cytochrome b(5) - A New Tool to Study the Cytochrome P450 Electron-transport Chain
- Oxidation of carcinogenic benzo[a]pyrene by human and rat cytochrome P450 1A1 and its influencing by cytochrome b5 - a comparative study
- Single Amino Acid Change in Metallothionein Metal-Binding Cluster Influences Interaction with Cisplatin
- Serum metallothioneins in childhood tumours-a potential prognostic marker
- Role of cytochromes P450 and peroxidases in metabolism of the anticancer drug ellipticine: additional evidence of their contribution to ellipticine activation in rat liver, lung and kidney
- DNA and histone deacetylases as targets for neuroblastoma treatment
- Assays for determination of matrix metalloproteinases and their activity
- Antioxidační aktivity nádorových buněk a vliv cytostatik na antioxidační status
- Analysis of thiol compounds and antioxidant activity in patients suffering from malignant disease
- Antioxidacni aktivita u nadorovych bunek, vliv cytostatika na oxidacni status
- Anticancer agent ellipticine combined with histone deacetylase inhibitors, valproic acid and trichostatin A, is an effective DNA damage strategy in human neuroblastoma
- Ellipticine cytotoxicity to cancer cell lines-a comparative study
- Optimalizace, detekce, interkalace a analyza DNA
- Determination thiolovych compounds and antioxidant activity in cancer patients
- Analysis of covalent ellipticine- and doxorubicin-derived adducts in DNA of neuroblastoma cells by the P-32-postlabeling technique
- Analysis of selected regulatory genes in prostate cancer cell lines
- A determination of oxidative stress in tumour cells treated with cytostatics
- Catalytic Electrochemical Analysis of Platinum in Pt-DNA Adducts
- Apoferritin Modified Magnetic Particles as Doxorubicin Carriers for Anticancer Drug Delivery
- Anticancer Efficiency of Reovirus in Normoxia and Hypoxia
- The Anticancer Drug Ellipticine Induces Cytochromes P450 1A1, 1A2 and 3A, Cytochrome b(5) and NADPH:Cytochrome P450 Oxidoreductase in Rat Liver, Kidney and Lung
- Close look at cytochrome P450-b5 catalytic complex
- Clinical importance of matrix metalloproteinases
- Cytochrome b(5) shifts oxidation of the anticancer drug ellipticine by cytochromes P450 1A1 and 1A2 from its detoxication to activation, thereby modulating its pharmacological efficacy
- Cytochrome P450-and peroxidase-mediated oxidation of anticancer alkaloid ellipticine dictates its anti-tumor efficiency
- Mechanisms of ellipticine-mediated resistance in UKF-NB-4 neuroblastoma cells
- Metallothionein electrochemically determined using Brdicka reaction as a promising blood marker of head and neck malignant tumours
- Metalothionein a jeho role v detoxikaci těžkých kovů a predispozici k chorobám
- Metallothioneins and zinc in cancer diagnosis and therapy
- Changes in MYCN expression in human neuroblastoma cell lines following cisplatin treatment may not be related to MYCN copy numbers
- Off-line coupling of automated pipetting system with square wave voltammetry as a tool for study of drug-DNA interaction
- %22Vinyl connection%22 - another mechanism of heme-apoprotein communication?
- Anthracyclines and ellipticines as DNA-damaging anticancer drugs: Recent advances
- Automated assay of natural antioxidants potency using pipetting robot and spectrophotometry
- The anticancer drug ellipticine induces cytochrome b5 and cytochromes p450 1a1, 1a2 and 3a in rat liver, kidney and lung
- Association of PSA level with thiols content in patients with prostate carcinoma
- Detekce sarkosinu v moci pacientu s karcinomem prostaty
- Cytochrome b(5) increases cytochrome P450 3A4-mediated activation of anticancer drug ellipticine to 13-hydroxyellipticine whose covalent binding to DNA is elevated by sulfotransferases and N,O-acetyltransferases
- Detection of selected miRNAs in prostate carcinoma
- Electrochemical Study of Doxorubicin Interaction with Different Sequences of Single Stranded Oligonucleotides, Part I
- Electrochemical Study of Doxorubicin Interaction with Different Sequences of Double Stranded Oligonucleotides, Part II
- Ellipticine oxidation and DNA adduct formation in human hepatocytes is catalyzed by human cytochromes P450 and enhanced by cytochrome b5
- Electrochemical characterization of doxorubicin interaction with DNA
- Effect of zinc(II) ions on the expression of pro- and anti-apoptotic factors in high-grade prostate carcinoma cells
- Protinadorove lecivo doxorubicin a jeho in vivo analyza fluorescencni mikroskopii
- The Role of Metallothionein in Oxidative Stress
- Study of fluorescence of doxorubicin in muscle tissue using highly sensitive fluorescence sensing
- Effect of Hepatic Cytochrome P450 (P450) Oxidoreductase Deficiency on 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine- DNA Adduct Formation in P450 Reductase Conditional Null Mice
- Efekt doxorubicinu a elipticinu na bunecne nadorove linie, rustove charakteristiky
- Exposure to benzo[a]pyrene of Hepatic Cytochrome P450 Reductase Null (HRN) and P450 Reductase Conditional Null (RCN) mice: Detection of benzo[a]pyrene diol epoxide-DNA adducts by immunohistochemistry and P-32-postlabelling
- From amino acids to proteins as targets for metal-based drugs
- Expression of Bcl-2 and other regulatory genes in tumour prostate cell lines
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