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V-ATPase expression in hypoxic conditions in neuroblastoma cells
Kittlerová, Kateřina ; Eckschlager, Tomáš (advisor) ; Moserová, Michaela (referee)
Tumor diseases belong to one of the most common death causes all around the world these days, therefore scientists still work on new therapeutic procedures. Tumor diseases are the second most common death causes among kids and juvenile. One of the freqeuently diagnosed tumor among kids and juvenile is neuroblastoma. Neuroblastoma is malignant embryonic tumor of the peripheral nervous system. Chemotherapy is used as tumor treatment by therapeutic procedures such as surgical removal and tumor irradiation. Cisplatin is one of the most applicated cytostatics, however it's efficiency it's lowered despite of creating resistance during the treatment. Vacuolar ATPase (V-ATPase) acidifies some of the cell organelles including lysosomes, which can lead to lysosomal sequestration of some of the substances including cytostatics and therefore the cure can't get to the therapeutic target. Key role in lysosomal activity regulation performes transcription factor EB (TFEB). This study deals with expression of d subunit of vacuolar ATPase (ATP6V0D1) and TFEB in neuroblastoma sensitive cell line UFK-NB-4 and resistant to cisplatin UKF-NB-4CDDP in normoxia and hypoxia. After exposure of neuroblastoma resistant cells to cisplatin the expression of ATP6V0D1 gene raised compared to normoxia. In case of TFEB the...
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Epigenetically based chemoresistance of cancer cells
Feriančiková, Barbara ; Eckschlager, Tomáš (advisor) ; Šácha, Pavel (referee)
Cancer, despite significant advances in diagnosis and treatment, is the second most common cause of death in economically advanced countries. The main reason for the failure of anticancer therapy is the development of chemoresistance, which can be either internal or acquired, and is primarily mediated by the activation of various key regulators (eg MDR, PI3K/Akt, etc.). Genetic and epigenetic mechanisms are involved in activating these pathwa- ys. Significant epigenetic mechanisms that can participate in chemoresistance include regula- tion of gene expression by microRNA (miRNA) and long noncoding RNA (lncRNA). Dere- gulated expression of these non-coding RNAs has been observed in many diseases and their involvement in the initiation and progression of malignant tumors has been demonstrated. In this study, we investigated the expression of long non-coding RNA MIAT in hypoxia (1% O2) in chemosensitive and chemoresistant neuroblastoma cell lines (NBL), as hypoxia is a significant negative prognostic factor of many tumors and is involved in chemoresistance. Relative expression of MIAT was influenced by the number of cultured cells, where expression was increased by culturing more cells. MIAT expression was also significantly increased after 6 hours of NBL culture UKF-NB-4 in hypoxic conditions, and...
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Biomarkers of prognosis and therapy efficacy in ovarian carcinoma
Cerovská, Ela ; Souček, Pavel (advisor) ; Schierová, Michaela (referee)
Ovarian carcinoma is a serious illness with the highest mortality rate among all female cancers. No suitable methods for early diagnosis, precise determination of prognosis or prediction of therapy efficacy are currently available, which leads to diagnosis in advanced stages of disease and therapy efficacy limitation. Consequently, the development of chemoresistance to conventional drugs and frequent relapse of the disease pose a fundamental complication too. The main goal of the current study was identification of new putative prognostic and therapeutic biomarkers, whose introduction into clinical practice could help to improve the dismal outcome of ovarian carcinoma patients. The present master thesis provides results of expression analysis of genes whose products take part in the transport, metabolism and mechanism of action of platinum based drugs and taxanes, and also the regulation of cell cycle and signaling. Transcript levels of these genes have been assessed in series of tumor and control ovarian tissue samples and the difference between both tissue types was evaluated. Gene expression level in tumors was then compared with patient's clinical data and candidate genes, ABCA2 and PRC1, were selected from the obtained results for more detailed analysis. The protein level of candidate genes...
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