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The role of cytochalasins in cancer cell migration and invasiveness
Brož, Alexandr ; Brábek, Jan (advisor) ; Bašta, Miroslav (referee)
While metastasis causes the majority of cancer related deaths, purely migrastatic drugs have been neglected in clinical research. This trend has been changing in recent years, with drugs capable of preventing metastasis, migrastatics, coming into focus. Cytochalasins are a large group of actin-directed fungal metabolites, often used for cytoskeletal and anticancer research. As the actin cytoskeleton plays a major role in tumour cell invasion and migration, processes integral in metastasis, it is possible that cytochalasins could have a future as migrastatics. The majority of cytochalasin-related research pertains to cytochalasin B and the more potent cytochalasin D, making both a large focus of this thesis, though the lesser researched cytochalasins A, E, H, Q and others are mentioned as well. Cytochalasins B and D have been shown to inhibit migration and invasion of cells with liposome encapsulation reducing side effects greatly, possibly enough to alleviate one of the main concerns of any cytochalasin therapy, toxicity. Though other cytochalasins have also been shown to inhibit cell motility, any conclusions as to their migrastatic translational potential are hard to draw due to the lack of research.
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Glycolytic enzymes and their inhibition in cancer cell invasiveness
Martinková, Eliška ; Peltanová, Barbora (advisor) ; Raudenská, Martina (referee)
Glycolysis, an essential metabolic pathway, serves to obtain energy from glucose. All ten enzymes, which are part of the glycolytic pathway, may be involved in processes that influence migration and the ability of tumor cells to invade surrounding tissues, which is closely related to the formation of metastases. Since the majority of patients with diagnosed solid tumors die because of complications associated with primary tumor metastases, studying this phenomenon is of great interest. The purpose of this thesis is to summarize the findings on the relationship between glycolytic enzymes and tumor cell invasion. Diverse roles of enzymes related to invasion, migration and metastases are described herein, ranging from influencing angiogenesis, cytoskeleton formation and mRNA and protein stabilization to affecting various signal cascades. Room is devoted not only to the relevant mechanisms at the molecular level but also to the results of research focused on therapy to date. The thesis also provides an overview of selected inhibitors of glycolytic enzymes that affect tumor cells invasion. Key words: invasion, migration, metastasis, glycolytic enzymes, inhibition, EMT, Warburg effect
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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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Biophysical interpretation of quantitative phase imaging of live cells generated by coherence-controlled holographic microscopy
Šuráňová, Markéta ; Rösel,, Daniel (referee) ; Vomastek, Tomáš (referee) ; Veselý, Pavel (advisor)
The dissertation thesis deals with the biophysical interpretation of quantitative phase imaging (QPI – Quantitative Phase Imaging) obtained using coherence-controlled holographic microscopy (CCHM – Coherence-Controlled Holographic Microscopy) in the Q-PHASE microscope, Telight, Brno). The theoretical part of this thesis deals with the characteristics of quantitative phase imaging, which provides non-invasive information on the activity of living cells in vitro. The main part of the work consists in elaborating a concept and verifying it of a new methodology (PAMP – Primary Assessment of Migrastatic Potential) for the first critical evaluation of drugs for expected anti-migratory/metastatic potential. The result of this method is considered the first sorting evaluation when considering specific migrastatic agents for future complex oncological treatment. PAMP evaluates the speed of cell migration, the growth of tumor cells and controls the risk of appearance of invasive phenotypes. Furthermore, the correlation microscopy method between the Q-PHASE microscope and the laser scanning confocal microscope (LSCM) is proposed to evaluate cell behavior and the occurrence of focal adhesions after drug application. The quantitative phase image obtained using the Q-PHASE microscope is compared with the quantitative phase image from the HoloMonitor (PHI AB, Sweden), on which the PAMP method has been positively verified.
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Study of the effect of migrastatics on the dynamics of tumour cell migration using a coherence-controlled holographic microscope
Muchová, Nikola ; Netíková,, Irena Štenglová (referee) ; Veselý, Pavel (advisor)
The thesis is focused on the exploitation of the coherence controlled holographic microscopy for the investigation of the influence of the supposed migrastatic drugs on the dynamics of cancer cell migration. The theoretical part briefly describes the history of holographic microscopy and the development of the holographic microscope at the Brno University of Technology in collaboration with Telight, Brno, including an insight into the design and principle of operation of the coherence-controlled holographic microscope. Next a brief description of current cancer treatments introduces new class of anti-cancer drug candidates designated migrastatics that should impair cancer cell migration and thus prevent late metastases formation. The main part of the thesis deals with the design of the experimental observation procedure and data processing using the holographic incoherent Quantitative Phase Imaging technique. The last part of the thesis is the subsequent analysis of the migrastatic effect of the selected drugs on cancer cells in vitro and the comparison of the obtained results with existing studies. Finally, the objectives with magnification 4x and 10x were evaluated and compared for starting “the Rapid Assessment of Cell Growth and Migration”.
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Analysis of brain tumors based on line of interest
Širůčková, K. ; Solár, P. ; Marcoň, P.
Due to the high resolution of soft tissue, magnetic resonance imaging plays a crucial role in the diagnosis and therapy planning in the neurosurgery field whereas it is necessary to determine which pathology in the brain tissue is involved. Glioblastoma multiforme, metastatic tumors and abscesses are examined in detail from magnetic resonance images. In clinical practice, all mentioned pathologies are diagnosed through invasive methods in the form of biopsy followed by histology of the affected tissue. This work is focused on an alternative non-invasive method of tumor diagnosis. The method is based on the data analysis from defined curves (drawn into the apparent diffusion images) that lead from the tumor area. The analysis of curves could lead to non-invasive diagnostics of the pathological tissue.
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Characterization of perinuclear actin fibers and their role in cell migration
Hlaváčková, Tereza ; Vomastek, Tomáš (advisor) ; Binarová, Pavla (referee)
Cell migration is crucial for such physiological and pathological processes as wound healing, emryonal development, immune response, and methastasizing of the cancer cells. It is tightly coupled with cell polarization, nuclear traslocation, and turnover of actin cytoskeleton. Substantial, but so far poorely explored, part of actin cytoskeleton is perinuclear actin cap - dome-like structure above the nucleus costructed from perinuclear actin fibers. At the apical side of the nucleus perinuclear actin fibers are associated with LINC complex through nesprin proteins; at the edges of the cell they are anchored to focal adhesions. In the literature there were assumptions that this type of actin fibers can generate traction forces for nuclear reorientation during cell migration. The aim of this thesis is to elucidate the mechanism involved in the attachment of perinuclear actin to the LINC complex and the nucleus, thereby regulating the formation of the perinuclear actin cap. In addition, we aimed to establish a semi- automatic tool for perinuclear actin fibers quantification. Rat2 fibroblasts were used as the model cell line because they contain well-developed perinuclear actin cap. We focused on the inactivation of LINC complex components, namely Giant nesprin proteins (nesprin 1 and nesprin 2) and...
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Drug repurposing for the inhibition of invasiveness and metastasis of cancer cells
Turchyna, Kateryna ; Brábek, Jan (advisor) ; Jakubek, Milan (referee)
Metastasis is the primary cause of death from cancer. Current lack of medicines for metastasis makes it a topical issue and encourages the global search for molecules that may potentially inhibit invasiveness of cancer cells, and thus prevent metastatic spread. Drug repurposing is a strategy of identifying new uses for approved drugs that are outside the scope of the original medical indication. The aim of this thesis is to summarize knowledge on the repurposing potential of selected groups of drugs with emphasis on molecular mechanisms of their action. In particular, the work is focused on selected antipsychotics, antidepressants, beta- blockers and statins, whose abilities to inhibit cancer invasiveness have been indicated.
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Study of the effect of migrastatics on the dynamics of tumour cell migration using a coherence-controlled holographic microscope
Muchová, Nikola ; Netíková,, Irena Štenglová (referee) ; Veselý, Pavel (advisor)
The thesis is focused on the exploitation of the coherence controlled holographic microscopy for the investigation of the influence of the supposed migrastatic drugs on the dynamics of cancer cell migration. The theoretical part briefly describes the history of holographic microscopy and the development of the holographic microscope at the Brno University of Technology in collaboration with Telight, Brno, including an insight into the design and principle of operation of the coherence-controlled holographic microscope. Next a brief description of current cancer treatments introduces new class of anti-cancer drug candidates designated migrastatics that should impair cancer cell migration and thus prevent late metastases formation. The main part of the thesis deals with the design of the experimental observation procedure and data processing using the holographic incoherent Quantitative Phase Imaging technique. The last part of the thesis is the subsequent analysis of the migrastatic effect of the selected drugs on cancer cells in vitro and the comparison of the obtained results with existing studies. Finally, the objectives with magnification 4x and 10x were evaluated and compared for starting “the Rapid Assessment of Cell Growth and Migration”.
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