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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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