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Synthesis, characterization and study of the properties of functional antibody conjugates
Stránská, Andrea ; Hrubý, Martin (advisor) ; John, Jan (referee)
Radioimmunotherapy combines biological treatment with the use of highly effective radioactive radiation, which allows for more effective and gentle cancer therapy. This bachelor thesis focuses on the use of the therapeutic radioisotope 161Tb, which is characterized by the emission of low-energy electrons and gamma rays that allow monitoring of therapy and targeting of cancer cells, metastases and whole tumors. This theranostic approach offers increased treatment efficacy, especially in the early stages of the disease. This thesis focuses on a model study of rituximab monoclonal antibody conjugates that have been fluorescently labelled using a fluorescein tag. Covalent binding between the immunotherapeutic conjugate and the fluorescent label was accomplished using free amino groups of lysines and bioorthogonal chemistry. A biologically active antibody conjugate with a fluorescent label was developed that allowed direct monitoring of the conjugate binding to CD20-expressing cells using confocal microscopy. Subsequently, a radioactive conjugate of rituximab, modified with the p-SCN-Bn-CHX-A"-DTPA chelator and radiolabeled with the 161 Tb radioisotope, was tested. The biological activity of the radioimmunoconjugate was determined by in vitro experiments. Biodistribution of the radioimmunoconjugate was...
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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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Evaluation of the Most Effective MRI Methods for a Diagnosis of the Brain Tumors
Širůčková, Kateřina
The purpose of this project is to find out the most effective method for a diagnosis of the brain tumors utilizing different magnetic resonance imaging methods. Acquired MRI images were analyzed in two diagnostic programs, and obtained data were displayed into ratio-graphs. According to the results, volume-ration images are considered the most sufficient. The advantage of this method is that it provides doctors with significant information regarding the differences of the measured values between healthy and pathological tissue.
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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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Arching
Willertová, Aneta ; Dolanová,, Lenka (referee) ; Klímová, Barbora (advisor)
The topic of this bachelor's thesis is the formation of so-called "personal mythologies" - subjective constructs of reality which are created spontaneously and naturally as a result of the need of inner and outer world interpretation. These constructs are built on the groundwork of experiences, impressions and memories, associating organically and creating unique bonds. The work put a goal to make this topic as an environment which will show the spectator those bonds, background of their formation and final mythologies as a selfportraits unit.
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Signal Processing for Diffusion Weighted Imaging
Petrek, Tomáš ; Bartušek, Karel (referee) ; Marcoň, Petr (advisor)
Diploma thesis explores the possibility of using diffusion-weighted images in medicine. The paper is a brief physical principle of operation of the magnetic resonance as a tool for non-destructive imaging of the internal structure of substances, the principle of the display contrast as T1, T2 and diffusion weighted images, the course of the sequence for obtaining images with different contrast. Medicine is faced with the problem of classification of pathological tissue in the brain. Contrast diffusion-weighted images does not visually determine the shape of pathological tissue in the form of a tumor or edema. With the T1 and T2 weighted images were calculated mask corresponding tumor and edema, that have been applied to the diffusion-weighted images. Images of the tumor and edema have been subjected diffusivity measurements and statistical evaluation for the purpose of classifying the type of tumor. Investigations were seven findings glioma and metastatic five awards. The research was focused on classifying pathological tissue.
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Microarray Data Interpretation
Ludwig, Petr ; Šilhavá, Jana (referee) ; Smrž, Pavel (advisor)
This Bachelor thesis explains the basics of biochip or microarray data interpretation, starting with short introduction to genetics, especially genetic information significance evaluating. The focus was set mainly on the set of scripts transforming and analyzing the sample data. The data used in this thesis are a result of biochip analysis of the Colon Tumor tissues. The secondary result represents disclosing the main marker for this particular type of cancer, the primary result is evaluation of marker significance in the context of signaling pathways. The resulting pathways are sorted by relevance.
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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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