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Anti-tumor activity of mesenchymal stem cells
Džuganová, Barbora ; Krulová, Magdaléna (advisor) ; Indrová, Marie (referee)
Mesenchymal stem cells (MSCs) are multipotent cells with the ability to migrate to inflammation sites and to tumor sites. They are able to regenerate the damaged tissues and also easy to isolate and cultivate. Furthermore, they can inhibit tumor cells and modulate the immune response. They are non-toxic in the organism and genetic modification of them can enhance their antitumor effect. MSCs can also serve as a vehicle for delivery of the therapeutic agent to the tumor. These properties make them special for anti-tumor therapy. Under some conditions, MSCs can also stimulate the tumor growth. This work discusses conditions in which MSCs inhibit the growth of cancer cells, as it is not yet clear on which precise mechanisms this inhibition is based.
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Physiological and pathophysiological role of GCPII in the body
Sedlák, František ; Konvalinka, Jan (advisor) ; Klener, Pavel (referee) ; Smetana, Karel (referee)
Glutamate carboxypeptidase II (GCPII) is a metalloprotease responsible for cleaving the neurotransmitter N-acetyl-aspartyl-glutamate in the central nervous system to N-acetyl aspartate and glutamate. At the same time, in the human small intestine, it facilitates folate absorption by cleaving γ-linked glutamate from folyl-poly-γ-glutamate. In humans, GCPII is also expressed in a number of other organs (e.g., kidney and prostate) and tumors, where its physiological function is unknown. In an attempt to characterize the physiological function of the enzyme, we first characterized the commercially available monoclonal antibodies against GCPII. Further, we developed a fully synthetic replacement based on a hydrophilic polymer with bound GCPII inhibitors. We evaluated the suitability of using a murine biomodel to study GCPII function in vivo. We found the difference in GCPII expression profile in mouse and human. We did not observe GCPII in either the mouse prostate or small intestine. To assess physiological and pathophysiological functions of the enzyme we analyzed a GCPII-deficient mouse model. Apart from the observation of enlarged seminal vesicles in older males, we did not detect any other obvious phenotype. Similarly, we confirmed that GCPII cannot cleave amyloid peptides (Aβ1-40 and Aβ1-42)....
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Immunogenic cell death in tumor specimens in the clinics
Fejfarová, Adéla ; Drbal, Karel (advisor) ; Büchler, Tomáš (referee)
Tumor development and growth are under the control of the immune system in the human body. Danger-associated molecular pattern (DAMP) molecules trigger the anti-tumor response by binding to pattern recognition receptor (PRR) on myeloid cells which in turn activate an adaptive immune system. DAMP molecules are released from cancer cells during a process of immunogenic cell death (ICD) which is a form of regulated cell death (RCD). ICD is induced by a variety of treatments in experimental settings as well as by therapeutic modalities commonly used in medicine. A typical DAMP marker of ICD is calreticulin which is translocated from the endoplasmatic reticulum to the plasma membrane attached to the CD91 receptor. Another marker is the nuclear protein HMGB1 which is released into the tumor environment at the later stage of ICD. This bachelor thesis describes a variety of detection methods and the results of DAMP externalization after ICD induction in vitro in cancer cell lines and in tumor specimens from cancer patiens. Moreover, the link between DAMP molecules and cancer patient survival is discussed. Last, it also summarizes the current status of clinical trials concerning ICD. Keywords tumor, antitumor immunity, cell death, adjuvans, DAMP, chemotherapeutics, immunogenic cell death, clinical trials
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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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Case Study of Physiotherapy Treatment of a Patient after ALPPS for leiomyosarcoma.
Čemusová, Kateřina ; Opatrná Novotná, Irena (advisor) ; Charvát, Robert (referee)
Author: Kateřina Čemusová Title: A case study of physiotherapy treatment of a patient after ALPPS for leiomyosarcoma. Aims: This thesis aims to record physiotherapy care for the patient after undergoing ALPPS treatment for leiomyosarcoma, determination, management and recording of individual therapeutic units, and evaluation of their effect. Methods: The thesis consist of a theoretical and practical part. The theoretical part consist of general information about the composition and physiology of the liver. Leiomyosarcoma and other liver diseases are also described. Lastly, the ALPPS method is mentioned. All information is cited from academic literature and other professional sources. The practical part contains a case report of a patient, who has undergone ALPPS treatment for leiomyosarcoma. It also contains the record of individual therapies, that have been performed based on a kinesiological analysis. The analysis has been done as a part of a physiotherapy intership at the Institute of clinical and experimental medicine in Prague from 18th January to 12th February 2021. Results: The treatment and the effect of therapeutic care were significantly slowed down due to the division of the surgery into two stages. In general, the dysbalances of muscle strength and hypertonia have been corrected. The...
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Immunogenic cell death
Šímová, Michaela ; Drbal, Karel (advisor) ; Javorková, Eliška (referee)
According to the danger model, the immune system is activated by endogenous molecules known as danger-associated molecular patterns (DAMP) that are externalized from the interior of a dying cell to the cell surface or released into the extracellular space. Due to the loss of plasma membrane integrity a necrotic cell death as well as several types of proinflammatory programmed cell death are considered to be immunogenic, whereas apoptosis, on contrary, has been initially defined as a tolerogenic type of cell death. However, under certain circumstances, the immune response can be initiated by an apoptotic cell after exnternalization of DAMP molecules by newly described secretory pathways. This phenomenon was observed on tumor cells as a result of some widely used therapeutic modalities and is known as immunogenic cell death (ICD). Nomenclature of selected types of cell death is part of this thesis. The aim of this bachelor thesis is to provide an evidence of the experimental support for ICD theory during in vivo initiation of the immune response. I will evaluate the correlation between ICD and the induced exposure of DAMP molecules on the surface of tumor cells or their secretion to the extracellular space.
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Healing wound as a model for the study of cell interactions
Gál, Peter ; Smetana, Karel (advisor) ; Motlík, Jan (referee) ; Brábek, Jan (referee)
Healing wound as a model for the study of cell interactions Abstract Galectins play an important role in the processes of cell proliferation, differentiation, migration and extracellular matrix formation. Furthermore, galectins are able to transfer cellular signals and to participate in cell interaction. It has been proven that galectins play an important role in the microenvironment formation of a tumor and/or healing wound. This study demonstrated significant role of galectins, in particular Galectin-1, in wound healing and cell interactions (endothelial cells, fibroblasts and keratinocytes) forming a part of the granulation tissue and tumor stroma. We have demonstrated that the extracellular matrix rich on Galectin-1 creates a suitable environment for the cultivation of keratinocytes. Galectin-1 also induces differentiation of fibroblasts into myofibroblasts. The knowledge of above mentioned processes is important to better understand the complexity of cancer biology and its parallel to wound healing. Key words: tissue repair, regeneration, galectin, tumor
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The expression of miRNA in HPV-associated and HPV-independent head and neck tumors
Vojtěchová, Zuzana
Head and neck cancers represent a group of tumors with two different etiologies. The first type is associated with the viral HPV infection, the second one is virus-independent and it is associated with smoking and alcohol consumption as two main risk factors. Numerous studies show that HPV-positive tumors are more frequent in younger patients, as well as that the prognosis and overall survival of these patients is remarkably better. Therefore, the modification of the treatment is considered. For this, however, specific, sensitive and clinically relevant biomarkers for accurate identification of tumor etiology is needed. Suitable candidates for such biomarkers are miRNAs, small non-coding regulatory molecules stable in archived samples, that have been shown as differentially expressed in human cancers and the expression pattern seems specific for tumors of different origin. The submitted thesis focuses on miRNA profiling in HPV-positive and HPV-negative tonsillar tumors and cervical carcinomas with the aim to find out the differences between regulation of important carcinogenetic pathways of tumors of viral and non-viral etiology. Our data have shown very large heterogeneity of the miRNA expression profiles of these tumors. Despite the well characterized and uniform samples collection, we have found...
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Analysis of circulating markers in patients with solid tumors
Buranovská, Katarína ; Souček, Pavel (advisor) ; Němcová, Vlasta (referee)
Circulating cell-free DNA (cfDNA) and its tumour-derived circulating tumour DNA (ctDNA) fraction are considered an innovative prognostic and predictive biomarker in oncological diagnostics. Many studies have demonstrated higher levels of cfDNA concentration and integrity, as an indicator of the amount of ctDNA in cfDNA, in body fluids from patients with cancer diseases in comparison with healthy individuals, which suggest its potential as an effective biomarker for monitoring of the tumour dynamics. This study focused on optimisation and validation of measurement methods later used for analysis of cfDNA concentration and integrity in blood samples from patients with four different solid cancers. Two different commercial isolation kits have been tested in plasma and serum samples. Quantitative real-time polymerase reaction (qPCR) and PicoGreen dsDNA assay were optimized to effectively quantify low concentrations of cfDNA, subsequently compared to each other and to droplet digital PCR assay tested on selected samples. The concentration and integrity of cfDNA from plasma samples of breast, ovarian, colorectal and pancreatic cancer patients were evaluated. Higher amounts of cfDNA were obtained by the QIAamp Circulating Nucleic Acid isolation kit (Qiagen) in comparison to Plasma/Serum Cell-Free...
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Oncolytic viruses in cancer immunotherapy
Zupko, Jakub ; Bartůňková, Jiřina (advisor) ; Janovec, Václav (referee)
Oncolytic virotherapy is a field dedicated to exploiting viruses in the battle against cancer, where their specific cytolytic effects are sorely needed. This work focuses on the mechanisms and limitations of oncolytic virotherapy, on the recent advances in the field and on the potential oncolytic viruses hold for the future.
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