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Detection of Pt derivatives using ICP mass spectrometry
Zelinová, Karin ; Hložková, Michaela (referee) ; Vašinová Galiová, Michaela (advisor)
This Bachelor´s thesis deals with the monitoring of chemotherapeutic penetration into tumor cells. Due to the toxicity of drugs, targeting them is absolutely essential from the point of view of minimizing the interference with healthy tissue of the patient. In order to achieve the best possible targeting, it is necessary to monitor the penetration of chemotherapeutics into cells. The subject of study was platinum-based drugs therefore the ICP-MS method was chosen to analyse the drug content in cells, because it is suitable for fast and reliable detection of trace amounts of elements. The theoretical part of the Bachelor´s thesis focuses on the description of ICP-MS, as a method, which was chosen for the detection of platinum derivates. It also summarizes the use of platinum-based drugs in cancer therapy. The practical part of the thesis deals with the analysis of cells exposed to platinum-based chemotherapeutics. Detection and quantification of platinum in the cells were determined by both SN-ICP-MS and LA-ICP-MS. To verify the results, the analysis of the solution was also performed by the AAS method. The results show, that the drug was most readily taken up by A2780 cells. It was also shown that cisplatin was the most accumulated drug.
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Cellular and molecular mechanisms of TRPC5 regulation
Ptáková, Alexandra ; Vlachová, Viktorie (advisor) ; Tureček, Rostislav (referee)
The TRPC5 ion channel is a molecular cold detector involved in the development of neuro- pathic and inflammatory pain in the peripheral nervous system. Its possible involvement in the mechanisms of the development of cold allodynia emerging as a side effect of chemotherapeutic treatment has not yet been investigated. The activation properties of the human TRPC5 receptor expressed in HEK293T cells in the context of exposure to low temperatures and oxaliplatin - widely used cytostatic drug, which side effects often manifest as a peripheral neuropathy trig- gered or enhanced by cold temperatures, were investigated using patch clamp electrophysiology and calcium imaging. Molecular modelling was used to explore possible mechanisms of action of oxaliplatin and lysophosphatidylcholine 18:1 whose levels are increased after oxaliplatin treatment. Low temperature (5 řC) decreased the amplitude of agonist-evoked membrane cur- rent responses and slowed down their deactivation. Analysis of single-channel recordings re- vealed increased open probability of the channel as well as prolonged mean open dwell time and reduced mean closed dwell time upon cooling. The highest temperature sensitivity of the gating of the channel was approximately between 16-11 řC with the corresponding value of the temperature...
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Detection of Pt derivatives using ICP mass spectrometry
Zelinová, Karin ; Hložková, Michaela (referee) ; Vašinová Galiová, Michaela (advisor)
This Bachelor´s thesis deals with the monitoring of chemotherapeutic penetration into tumor cells. Due to the toxicity of drugs, targeting them is absolutely essential from the point of view of minimizing the interference with healthy tissue of the patient. In order to achieve the best possible targeting, it is necessary to monitor the penetration of chemotherapeutics into cells. The subject of study was platinum-based drugs therefore the ICP-MS method was chosen to analyse the drug content in cells, because it is suitable for fast and reliable detection of trace amounts of elements. The theoretical part of the Bachelor´s thesis focuses on the description of ICP-MS, as a method, which was chosen for the detection of platinum derivates. It also summarizes the use of platinum-based drugs in cancer therapy. The practical part of the thesis deals with the analysis of cells exposed to platinum-based chemotherapeutics. Detection and quantification of platinum in the cells were determined by both SN-ICP-MS and LA-ICP-MS. To verify the results, the analysis of the solution was also performed by the AAS method. The results show, that the drug was most readily taken up by A2780 cells. It was also shown that cisplatin was the most accumulated drug.
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The study of the factors affecting colorectal cancer chemotherapy
Dolníková, Alexandra ; Opattová, Alena (advisor) ; Václavíková, Radka (referee)
Application of cytotoxic chemotherapy still remains the essential treatment strategy in advanced colorectal cancer. The intrinsic and acquired drug resistance represents one of the reasons that may even lead to failure of cancer therapy. The DNA damage response pathways have been shown to play an important role in the development of chemoresistance. There is sufficient evidence showing the high-frequency deregulated expression of many DNA repair genes across multiple cancer types. An example of such gene in colorectal cancer is MRE11, which encodes protein known as a sensor of DNA double-strand breaks. In year 2016, there was a substantial study published by our group at The Department of Molecular Biology of Cancer (IEM CAS, Prague), the study analysed the association of polymorphisms in predicted microRNA target sites of double-strand breaks (DSBs) repair genes, including MRE11, and clinical outcome and efficacy of chemotherapy in colorectal cancer. Our hypothesis, based on the mentioned study, is that specifically and exactly defined microRNAs with ability to regulate certain DNA repair proteins may not only affect the survival of colorectal cancer cells, but also the sensitivity to chemotherapy. In practical part of the submitted thesis we have identified miR-140 as a potential regulator of...
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