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Design, preparation and structural studies of biologically relevant protein variants of cancer-related Carbonic Anhydrase IX
Fejfarová, Adéla ; Maloy Řezáčová, Pavlína (advisor) ; Novotný, Marian (referee)
3 Abstract Carbonic anhydrase IX (CA IX) represents an attractive target for the development of anticancer drugs as it is overexpressed in various types of solid tumors. By its catalytic activity, CA IX assists the cancer cells to maintain the optimal intracellular pH and to acidify the extracellular milieu promoting tumor development. There are twelve enzymatically active carbonic anhydrases (CAs) present in human body, all sharing a high sequence identity and a typical β-sheet structural fold of the well-studied catalytic domain. Although, the activity of CAs is efficiently inhibited by sulfonamide-containing compounds, the design of inhibitor selective to the cancer-related CA IX has been hampered by the high sequence conservation. CA IX has several unique features compared to other members of the family, which investigation may help in the development of selective drug compounds. Namely, it is a type I transmembrane dimeric protein with unique N-terminal proteoglycan-like (PG) domain, extracellular catalytic domain, and short cytoplasmic C-terminal segment. The above denoted traits make CA IX subject of structure-based drug design efforts. However, the expression and purification in high yield as well as crystallization experiments has been challenging. Therefore, protein variant bearing six amino acid...
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Radiotherapy planning
Požár, Pavel ; Sekora, Jiří (referee) ; Kolářová, Jana (advisor)
This thesis deals with analysis of characteristics of ionising radiation. The equipments used for irradiation of pathologic findings are described. The thesis contains particular stages of planning algorithm with list of individual actions. Practical part contains a description of application made for irradiation simulation which includes brief explanation of working procedure with program. It also contains a description of individual functions of this application.
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Time development analysis of treated lesion in spinal CT data
Nohel, Michal ; Jan, Jiří (referee) ; Jakubíček, Roman (advisor)
This diploma thesis is focused on time-development analysis of treated lesion in CT data. The theoretical part of the thesis deals with the anatomy, physiology, and pathophysiology of the spine and vertebral bodies. It further describes diagnostic and therapeutic options for the detection and treatment of spinal lesions. It contains an overview of the current state of usage of time-development analysis in oncology. The problems of the available databases are discussed and new databases are created for subsequent analysis. Futhermore, the methodology of time-development analysis according to the shape characterization and the size of the vertebral involvement is proposed. The proposed methodological approaches to feature extraction are applied to the created databases. Their choice and suitability is discussed, including their potential for possible usege in clinical practice of monitoring the development and derivation of characteristic dependences of features on the patient's prognosis.
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Methods of Detection, Segmentation and Classification of Difficult to Define Bone Tumor Lesions in 3D CT Data
Chmelík, Jiří ; Flusser,, Jan (referee) ; Kozubek, Michal (referee) ; Jan, Jiří (advisor)
The aim of this work was the development of algorithms for detection segmentation and classification of difficult to define bone metastatic cancerous lesions from spinal CT image data. For this purpose, the patient database was created and annotated by medical experts. Successively, three methods were proposed and developed; the first of them is based on the reworking and combination of methods developed during the preceding project phase, the second method is a fast variant based on the fuzzy k-means cluster analysis, the third method uses modern machine learning algorithms, specifically deep learning of convolutional neural networks. Further, an approach that elaborates the results by a subsequent random forest based meta-analysis of detected lesion candidates was proposed. The achieved results were objectively evaluated and compared with results achieved by algorithms published by other authors. The evaluation was done by two objective methodologies, technical voxel-based and clinical object-based ones. The achieved results were subsequently evaluated and discussed.
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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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High Voltage Pulse Generator for Electroporation of Cells
Puczok, Václav ; Martiš, Jan (referee) ; Červinka, Dalibor (advisor)
The main goal of this thesis is to design control board for the experimental electroporation device and to develop control firmware. The first chapter of this work focuses on the electroporation phenomenon itself. Behaviour of the cell model in external electrical field is described there as well as simulation and overview of how electroporation affects living tissue. It also explains the main requirements for parameters of the electroporation pulses as well as need for ECG synchronization. Furthermore, some remarks are given about novel high frequency electroporation method, which involves use of nanosecond bipolar high voltage pulse bursts. The second chapter briefly introduces commercial electroporation device called Nanoknife, including control part, power part, and it's limits. The third chapter consists of introduction of the novel experimental electroporation device developed at BUT. Power part of this device is discussed as well. Next chapter focuses on design of the control board for this device and also on description of the particular schematic parts. There is a control algorithm explanation in the fifth chapter of this thesis followed by the brief manual to machine operation.
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The effect of therapeutical ultrasound and metalic nanoparticles on carcinoma cells
Kalužová, Adéla ; Rozman, Jiří (referee) ; Bernard, Vladan (advisor)
This thesis focuses on the research of an effect of ultrasound and nanoparticles on cancer cells. In the literature search there the applications of ultrasound field in the interaction with aplication of metallic nanoparticles to viability of cancer cells are described, on the basis of in vitro experiments‘ performance. The purpose of metallic nanoparticles‘ application should be a possible reinforcing of its antitumor effect thanks to the presence of ultrasound field. In next part of the literature search there are included the technical performance of devices, their indications and contraindications, parameters of ultrasound fields and application of metallic nanoparticles. The metallic nanoparticles have been becoming a part of the human’s life more and more, that is why it’s necessary to deal with these miniature particles at a higher level. The aim of this thesis is to suggest the ways of resolution based on the principle of sounding of cells with the ultrasound field of suitable parameters and in combination with the application of metallic nanoparticles with a successive performance of the cell viability tests. The viability was determinated by the MTT assay test. Another part of this work is the measurement of parameters of this zone by means of a submersible needle hydrophone, for a better understanding of the ultrasonic zone. In the final part of this work there is necessary the statistical evaluation of the measured data of the experiments carried out and the discussion of the results obtained.
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Enzymy pro aktivaci protinádorových proléčiv
Kubináková, Nikol
The current issue of oncological therapy lies in its effectiveness and severe side effects. Despite the most modern devices available for treatment methods, cancer treatment is very challenging. Chemotherapy uses highly toxic substances, which results in side effects that can only aggravate the patient. These side effects very often limit the dose of the drug, so that it is not possible to achieve such a concentration that would completely eradicate the tumor in the body. The answer to the question of how to overcome or reduce the occurrence of side effects in cancer treatment is prodrug therapy, which includes less toxic substances/drugs. This therapy aims to target cytotoxic drugs to a non-toxic derivative or prodrug. Prodrugs are inactive and bioreversible derivatives of active drugs that function as a concept for improving active drugs. After administration of the prodrug, this prodrug is selectively activated by enzymes (Cytochromes P450), resulting in the regeneration of the toxic parent drug at the site of the tumor.
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Robotic Neurosurgery Planning Tool
Sadleková, Simona ; Olivová, Jana (referee) ; Kadlec, Petr (advisor)
Táto diplomová práca sa zaoberá problematikou plánovania robotických operácií pre neurochirurgiu a optimalizačnými algoritmami používanými na návrh operačných zákrokov nimi prevádzaných, predovšetkým algoritmom VNDMOPSO. V úvodnej kapitole je vysvetlený základný princíp prevádzania robotických operácií a popísaný koncentrický trubicový robot používaný pre tento účel. Ďalej sa práca zaoberá všeobecným popisom optimalizačných problémov a algoritmov ich riešiacich a následne je podrobne popisovaný algoritmus VNDMOPSO, vybraný pre daný optimalizačný problém. Pre tento algoritmus je vytvorená v prostredí MATLAB funkcia, ktorá je následne testovaná na viacerých testovacích úlohách. V nasledujúcich častiach je overovaná jej funkčnosť na reálnych tvaroch nádorov a je predstavené grafické užívateľské prostredie, ktoré slúži ako nástroj pre plánovanie neurochirurgických robotických operácií. V záverečnej časti práce je vyhodnotený vplyv nastavenia jednotlivých parametrov algoritmu na výsledky optimalizácie.
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Spontánní regrese rakoviny
RADOVÁ, Lenka
The main goal of this thesis is to find and gather documented cases of spontaneous cancer regression without targeted therapy. Based on the case studies, this thesis aims to categorize individual cases and explain spontaneous regression at the immunological level. According to the findings, we will attempt to evaluate whether the observed cases of cancer regression would find experimental or clinical use.
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