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National Repository of Grey Literature 2 records found  Search took 0.00 seconds. 
Use of polymer prodrugs containing cucurbitacin D for the treatment of experimental tumors
 Hrabánková, Klára ; Šírová, Milada (advisor) ; Grobárová, Valéria (referee)
Chemotherapy is still the most widely used anti-cancer treatment. The majority of chemotherapeutics inhibit proliferating cells generally, not selectively cancer cells. The side effects associated with chemotherapy can be partly limited by conjugating a cytotoxic drug with a polymer nanocarrier. Such binding facilitates solubility in aqueous solutions, reduces systemic toxicity; and passively targets the drug directly into the tumour through the enhanced permeability and retention (EPR) effect. This thesis focuses on testing polymer conjugates based on N-(2-hydroxypropyl)methacrylamide (HPMA) carrying cucurbitacin D (CuD), a naturally occurring compound with potential anti-cancer activity. The mechanism of action is not elucidated yet, but several studies have depicted the inhibitory effect on signal transducer and activator of transcription 3 (STAT3) transcription factor. A STAT3 signalling pathway is overexpressed in several cancer cell lines and is also involved in the differentiation of myeloid- derived suppressor cells (MDSCs). We examined the therapeutic effect of the HPMA copolymers based on CuD in combined therapy with other polymer chemotherapeutics. CuD conjugates have shown in vitro cytotoxic effect on several model cancer cell lines. The combination with conjugates carrying doxorubicin...
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The role of indoleamine 2,3-dioxygenase in tumor progression and it's therapeutic targeting
 Hrabánková, Klára ; Šírová, Milada (advisor) ; Čermák, Vladimír (referee)
Indoleamine 2,3-dioxygenase (IDO) is an enzyme that is physiologically expressed in many tissues including small intestine, lung, female genital tract and placenta. It is a key enzyme in metabolism of tryptophan and catalyses the first rate-limiting step in the conversion of tryptophan to kynurenine. IDO plays an important role in immune system in fighting against various pathogens. Its expression is actively induced by inflammatory mediators and it has also an immunosuppressive function. Inducible counter-regulation of inflammation is very important for controlling its potential harmful effects. Depletion of tryptophan and production of kynurenines causes local suppression of effector T lymphocytes and activation of regulatory T cells. It can also support differentiation of dendritic cells toward an immunosuppressive phenotype. IDO expression has been observed in several cancer cell types including acute myeloid leukaemia, ovarian cancer or colorectal carcinoma and plays a major role in suppression of anti-tumour immunity. Thus, the inhibition of IDO may improve the efficacy of chemotherapy and immunotherapeutical protocols. Some IDO inhibitors are currently being tested in clinical trials and preliminary results seem promising so that it may become a new anticancer strategy. Key words indoleamine...
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