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Identification of expression profile changes of resistance-associated genes in experimental in vivo model of ovarian carcinoma
Bryndová, Barbora ; Václavíková, Radka (advisor) ; Dračínská, Helena (referee)
Ovarian carcinoma is one of the most serious gynecological malignancies in the world. High mortality of this cancer is mainly due to the development of multiple drug resistance to conventional treatments involving taxanes. Therefore, current research is focused on the study of new taxane-based derivatives capable to overcome known mechanisms of drug resistance. At present, there are several promising Stony Brook taxane derivatives (SB-T-taxanes), investigated in frame of efficacy, toxicity and mechanism of action. The aim of this bachelor thesis was to study changes in the expression of genes involved in the development of resistance in tissues and tumor obtained from in vivo mo- dels after the administration of derivatives SB-T-121605 compared to conventional taxane paclitaxel and non-treated models. Expression of selected ABC transporter genes (ABCB1, ABCC1 and ABCG2), taxane metabolizing enzyme genes (CYP3A11, CYP3A13 and CYP2C29) and their mouse orthologs was estimated in liver, intestinal and tumor tissue samples taken from in vivo mouse xenograft models. Tumor tissue was derivated from the highly resistant NCI/ADR-RES ovarian cancer cell line. Gene expression was determined by real-time quantitative polymerase chain reaction. Administration of the SB-T-121605 derivative led to several...
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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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Hidden malnutrition in patients with advanced stage of ovarian carcinoma
Ožanová, Michaela ; Tuček, Štěpán (advisor) ; Kostková, Lenka (referee)
This diploma thesis deals with the topic of hidden malnutrition in patients with advanced stage of ovarian carcinoma. Tumor diseases are often accompanied by malnutrition. In the case of ovarian cancer, malnutrition may be hidden, primarily due to ascites, which can distort body weight. Out of the patients included in this study 32 % had ascites. The basic nutritional status test in hospitals is the nutritional screening performed on each hospitalized patient to detect the risk of malnutrition. Other methods such as anthropometric measurements, laboratory values, bioimpedance analysis, or less commonly, imaging processes can also be used to detect malnutrition. The aim of this thesis was to evaluate whether nutritional screening and regular weight control in patients with advanced ovarian cancer is sufficient to diagnose malnutrition. The results have shown that the inclusion of anthropometric measurements between routine screening can be beneficial in detecting a greater number of malnourished patients. Also shifting the BMI threshold in nutritional screening for patients over 65 would greatly increase the capture of patients at risk of malnutrition. The secondary focus was to find whether the presence of ascites can be a determining factor in malnutrition being left undiagnosed, and which simple...
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Molecular characteristics of mismatch repair pathway in ovarian cancer
Burócziová, Monika ; Vodička, Pavel (advisor) ; Schierová, Michaela (referee)
In humans, multi enzymatic processes are involved in maintaining DNA stability and cellular homeostasis. Cells undergo several episodes to survive and protect itself in daily basis. Accumulation of DNA errors and breaks are repaired by dynamic machinery, such as mismatch repair (MMR), replication-related process. In presented diploma thesis, we report the studied MMR pathway and its involvement in malignancy of epithelial ovarian cancer (EOC). Our working hypothesis postulated that core genes of MMR, such as MLH1 and MSH2 are down-regulated in malignant cells. Cells therefore become incapable to repair accumulating DNA damage, undergo apoptosis or most likely uncontrolled proliferation. Above mentioned genes may also be silenced in cancer patients at transcription, translation or epigenetic levels. Our aims were to clarify and to investigate the importance of MMR based on mRNA transcription, protein stability and promoter hypermethylation on a set of major MMR genes, particularly MLH1, MSH2, PMS1, MLH3, MSH6, MSH3, and PMS2. In our study, we analysed samples from 63 epithelial ovarian cancer patients and 12 non-malignant reference tissues using RT-qPCR, MS-HRM, and Western Blotting methods. Consequently, our results show down-regulation of all MMR genes except for MSH2 (up-regulated) in tumor...
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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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Immunotherapy of ovarian carcinoma with dendritic cells
Partlová, Simona ; Rožková, Daniela (advisor) ; Froňková, Eva (referee)
V ANGLICKÉM JAZYCE Immunotherapy of ovarian carcinoma with dendritic cells Anticancer immunotherapy is a therapeutical strategy aimed at elicitation and maintenance of immune responses against cancer cells. In this study we have focused on immunotherapy of ovarian cancer, because it is one of the most common gynaecological tumors with poor prognosis and high mortality. Our immunotherapy protocol involves preparing dendritic cells (DC) from monocytes isolated from patient's peripheral blood, which are subsequently pulsed with irradiated cells of established ovarian cancer cell line. These immature pulsed DC are maturated and subsequently co-cultivated with autologous T lymphocytes. The aim of this study was to demonstrate, that DC are able to elicit specific immune response after addition of suitable mature agens in combination with apoptotic ovarian tumor cells. Our observations indicate that 24 hours are sufficient for induction of tumor cells apoptosis. Additionally, we have shown that DC successfully ingested most of the apoptotic tumor cells after 4 hours of co-incubation. Furthermore, we have found out that ingestion of apoptotic cells by dendritic cells, which are stimulated with polyI:C, inhibits maturation of DC and consequently also production of cytokines IL-12p70, IL-6 and TNF-α. Whereas...
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