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The effects of a molecular change caused by new taxanes in experimental models and patients with solid tumors
Koucká, Kamila ; Stiborová, Marie (advisor) ; Dračínská, Helena (referee)
Ovarian cancer is the most common cause of death from gynecological malignancy. Taxanes and platinum derivatives are most used therapeutics for its treatment. Development of multi drug resistance to chemotherapy represents a serious complication of the treatment. Therefore, new chemotherapeutic and therapeutic targets are investigated, which could help to overcome tumor cell resistance. The main objectives of the thesis were to study: i) the efficiency of new derivatives of conventional taxanes in vitro with the aim to determine the potentially most effective taxane derivatives in resistant tumor ovarian cells and, ii) the gene expression profile of the Notch signaling pathway, as a possible therapeutic target for the treatment of ovarian cancer. Specifically, the thesis focused on the relationship between levels of Notch signaling gene expression in patients with ovarian carcinoma and their prognosis, progression and survival. This thesis revealed that Stony Brook Taxanes - "SB-T"; SB-T-121402, SB-T-121605, and SB-T-121606 derivatives are very effective in NCI/ADR-RES tumor carcinoma cells resistant to conventional taxane - paclitaxel, and should be further studied in more advanced models, e.g. in vivo patient derived xenografts. In a study of the importance of the Notch signaling pathway in...
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Study of effect of flavonoids on biotransformation enzymes expression
Koucká, Kamila ; Moserová, Michaela (advisor) ; Mrízová, Iveta (referee)
Flavonoids belong to the group of phenolic compounds included in the secondary metabolites of plants, which are represented mainly in fruits and vegetables. These compounds have antioxidant and anti-carcinogenic effects. Some of them can affect biotransformation enzymes, which include the cytochrome P450 and can interfere with the metabolism of xenobiotics. In the present work we studied effect of dihydromyricetine on the gene expression of cytochrome P450 1A1, 1A2 and cytochrome b5 in livers, lungs, kidneys, colon and small intestine of laboratory rats. The small intestine was divided into three parts namely a proximal, middle and distal. At first, isolation of total RNA was made using commercial reagents and isolated RNA was converted to cDNA by reverse transcription. Finally, using polymerase chain reaction in real time (RT-PCR), the relatively gene expression of genes observed in the organs of laboratory rats pretreated dihydromyricetine and control laboratory rats (untreated) to a reference gene β-actin was determined. It was found that dihydromyricetine did not significantly affect the gene expression of studied genes in most organs. However, a significant decrease of gene expression of CYP1A1 and CYP1A2 was observed in the lungs. On the contrary, an increase of gene expression of CYP1A2 was...
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