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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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Methylation of the regulatory sequences of integrated and extrachromosomal form of HPV 16 in tonsillar tumors
Pokrývková, Barbora ; Tachezy, Ruth (advisor) ; Hubáček, Petr (referee)
Human papillomavirus is connected with induction of cervical carcinoma as well as for some other anogenital carcinomas and subset of carcinomas of head and neck. Presence of viral E6 and E7 oncoproteins may induce cell transformation, higher load of oncoproteins is caused by the regulatory E2 protein inactivation. Aims of recent study are mechanisms of E2 protein inactivation. One option is integration of viral DNA into the host genome, which is located into the E2 gene region. Some carcinomas, where virus with extrachromosomal form was presented, were found. It appears that epigenetic changes can play the role in the development of this type of tumors, especially DNA methylation or mutation in the regulatory region of the virus. The methylation degree analysis on samples of tonsillar carcinomas with extrachromosomal and integrated form of the virus was conduced, as well as viral load of both groups was compared and the expression of E6 and E7 gene was confirmed. The results of methylation analysis showed increased methylation of the virus with integrated DNA. Mutations in the E2 protein binding sites are not revealed. The expression of the viral oncogenes were confirmed in all tumors regardless of the form of the viral genome. The mechanism of tumors induction, especially for virus with...
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Free circulating nucleic acids in plasma
Totzauerová, Kateřina ; Beránek, Martin (advisor) ; Šimůnek, Tomáš (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Kateřina Totzauerová Supervisor: Doc. PharmDr. Martin Beránek, Ph.D. Title of diploma thesis: Free circulating nucleic acids in blood plasma Outline: The aim of this thesis was to compare various commercially available DNA extraction kits and choose the universally optimal method for routine isolation of free circulating DNA from blood plasma samples according to their optical characteristics, the qPCR results and yield of short fragments. Methods: Four commercially available methods of extraction have been chosen to compare: QIAmp DNA Blood Mini Kit, QIAmp DSP Virus Spin Kit (both Qiagen), NucleoSpin Plasma XS (Macherey-Nagel) and Agencourt Genefind v2 (Beckman Coulter). DNA was isolated from aliquots of a pooled blood plasma of healthy individuals. Plasmatic DNA was quantified after extraction by spectrophotometry, fluorimetry and quantitative polymerase chain reaction. Fragmentation analysis on selected samples by capillary electrophoresis was also realized. Results: The best yield and purity provided the method from Qiagen QIAmp DSP Virus Spin Kit. Average value of the concentration determined qPCR was 49.95 ± 23.57 ng/mL and it gave the highest values of the fluorescence of...
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Immunocomplexes of IL-2 and anti-IL-2 mAbs as a novel class of selective and extremely potent immunostimulators
Tomala, Jakub ; Kovář, Marek (advisor) ; Smetana, Karel (referee) ; Špíšek, Radek (referee)
vi ABSTRACT IL-2 has been used in cancer therapy and also for other applications like treatment of chronic viral infections or as an adjuvant for vaccines. However, treatment with IL-2 is rather difficult due to its severe side effects. These toxicities, associated with high-dose treatment necessary for IL-2 to function, have been found the most limiting factor for IL- 2 applications. Further, particular anti-IL-2 monoclonal antibodies (mAb) can actually increase biological activity of IL-2 rather than block it. Binding of IL-2 to anti-IL-2 mAb creates a superagonistic immunocomplexes which have dramatically higher and selective biological activity in comparison to free IL-2 in vivo. Such approach may finally over- come the difficulties associated with administration of IL-2, thus opening brand new scopes for IL-2 and its application not only in the field of tumor therapy. We have shown that IL-2 immunocomplexes composed of IL-2 and anti-IL-2 mAb S4B6 (IL-2/S4B6) stimulate predominantly cells expressing CD122 and CD132 (dimeric IL-2 receptor), i.e. NK and MP CD8+ T cells, with Treg, T and NKT cells being expanded as well. IL-2/S4B6 are able to drive the expansion of activated naive CD8+ T cells into functional memory-like CD8+ T cells. Moreover, these immunocomplexes exert therapeu- tical potential alone...
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Extracellular microRNAs in hematological malignancies and their use for diagnosis and treatment monitoring
Šulcová, Dominika ; Pospíšil, Vít (advisor) ; Čermák, Vladimír (referee)
MicroRNAs are short non-coding RNAs that negatively regulate gene expression at post-transcriptional level by interfering with mRNA translation and stability. Recently, microRNAs were surprisingly found to be present in various body fluids including blood plasma and serum, cerebrospinal fluid, saliva, milk or urine. These extracellular microRNAs are resistant to RNases and stable in high temperature or pH. Extreme stability of extracellular microRNAs is caused by their association with protective protein complexes (mostly with Argonaute proteins). MicroRNAs are frequently deregulated in cancer and specific tumor- related microRNAs can be also detected in body fluids, indicating that extracellular microRNAs can be used as tumor specific markers. This Bachelor thesis reviews basic principles of microRNA function and biogenesis with focus on extracellular microRNAs and their role in intercellular communication, and it highlights the role of extracellular microRNAs in hematological malignancies and their possible use in diagnosis and treatment.
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Case report of therapeutic care patient after brain tumor surgery in the temporal lobe
Soukup, Petr ; Křížková, Štěpánka (advisor) ; Kozáková, Alena (referee)
Title: Case report of therapeutic care patient after brain tumor surgery in the temporal lobe Object of paper: The primary aim of this work is to describe the subject of CNS - tumors lokalized in the brain, specifically in the temporal lobe and subsequently a case study of a patient with this diagnosis, which was established during a hospital university-internship. Abstract: The general part deals with the theoretical information about the nervous system and brain tumors. Where as the specific part shows a case report of pateint after a brain tumor surgery in the temporal lobe. The materialis and the fundation of this bachelor dissertation were gathered at the neurological in-patient ward in regional hospital Kladno. Key words: Tumor, physiotherapy (physical therapy), central nervous system, temopral lobe (lobus temporalis)
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Role of STAT3 signalling in oncogenesis and cancer therapy
Machalová, Veronika ; Hodný, Zdeněk (advisor) ; Brábek, Jan (referee)
STAT3 (Signal Transducer and Activator of Transcription 3) is considered to be one of the possible targets of cancer treatment. The ability of STAT3 constitutive activation to form tumors is a foundation of such theories. Additionally, constitutively activated STAT3 is present in many types of cancer with high occurrence, such as breast and prostate carcinoma. This protein is required in normal body cells as well. STAT3 is a transcription factor targeting many genes that are essential for the cell. STAT3 is activated by phosphorylation of its tyrosine residue and homodimerization. Proteins transcribed with help of STAT3 function in cell cycle progression, cell growth, replication, negative regulation of apoptosis, and other roles, typical for cancer. Moreover, STAT3 is modulating mitochondrial function and maintaining ROS production in mitochondria, but in form of transcriptionally inactive monomers. The purpose of this Thesis is to review known data about STAT3 in oncogenesis and by that, to show STAT3 has great potential to become the target of cancer treatment. This Thesis contains a short overview of known STAT3 inhibitors as well. Key words: Signal Transducer and Activator of Transcription 3 (STAT3), JAK/STAT3 pathway, constitutive activation, cancer, tumor, inhibitor, mitochondria, apoptosis
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Leukemic stem cells
Vobořil, Matouš ; Stöckbauer, Petr (advisor) ; Šídová, Monika (referee)
The biology of stem cells came to the foreground not only due to scientific but also due to clinical interest and it is one of the most developing fields of current biomedical research. The idea, that all tumor cells contain population of cells like stem cells, leads to the "cancer stem cells hypothesis". It says, that each tumor cell contains small population of cells capable to initiate and maintain the tumor growth. Tumors of the hematopoietic tissue were the first, where cancer or leukemic stem cells were isolated. Therefore, leukemic stem cells are so far the best understood cancer stem cells. However, despite the huge advances in the biology of leukemic stem cells, there are many properties still unknown. This thesis initially presents basic knowledges in the stem cell biology, including their origin and identification. Later it focuses on the stem cell hypothesis and describes of the main properties of stem cells in solid tumors. The main part of this thesis also shows in details the origin and properties of the leukemic stem cells and decribes some new directions in the targeted therapy of hematological malignancies.
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Recombinant vaccinia virus for cancer therapy, the analysis of biological and biochemical features.
Žůrková, Kamila ; Němečková, Šárka (advisor) ; Forstová, Jitka (referee) ; Trejbalová, Kateřina (referee)
151 8 SUMMARY Recombinant vaccinia virus has been used for elicitation of the immune response against expressed heterologous proteins which has led to protection of the host organisms against the agents producing that antigen (viruses, cancer cells). In our laboratory, we designed and evaluated several vaccines against cancer caused by human papillomavirus type 16 (HPV16). Vaccinia viruses derived from replication competent strain P13 or attenuated MVA were used for construction of recombinant viruses expressing HPV16-E7 in highly immunogenic fusion construct SigE7LAMP. Recombinant viruses were used both in prophylactic and therapeutic settings in mouse tumor models using TC-1 or TC-1/A9 cells. The genes encoding stimulatory cytokines GM-CSF or Flt3 ligand were inserted into the above viruses to support the immune system and to potentiate the anticancer response. Tumor microenvironment was modified using the recombinant viruses expressing both the E7 gene and soluble receptor for TGF-β which should decrease the inhibition of immune system caused by tumor TGF-β cytokine and elicit the response against tumor cells. Intratumoral or intraperitoneal administration of viruses enhanced anticancer response in mice, the viruses expressing Flt3 ligand induced the proliferation of E7- specific cytotoxic T lymphocytes....
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Health and social care for cancer patients in university hospital Pilsen
RATHOVÁ, Lucie
The bachelor thesis focuses on the health and social problem of oncologically ill patients in Plzeň university hospital. The thesis is divided into a theoretical and an empiric part. The theoretical part of the thesis is focused on the occurence of oncological illnesses and gender distribution. Further on, the theoretical part describes some of the examination methods, the causes of oncological illness origin and subsequently it deals with the social influence on the patient who is oncologically ill and under palliative care. In the last section of the theoretical part health and social services provided by the University Hospital in Plzeň for oncologically ill patients are described. The goal of the practical part was to describe the problem of oncologically ill patients in the Plzeň University Hospital from a multidisciplinary care point of view. To gain information I used the methodics of a qualitative research. Semi-structured interviews were used as a tool for the research. Semi-structured intervews were carried out with ten patients who were getting treatment in the Plzeň University Hospital. Research questions were the following. How do patients in the oncological department perceive the care provided? What problem within multidisciplinary care do patients perceive as the most serious one? The result of the thesis is the finding that patients in Plzeň University Hospital are satisfied with health care, with the treatment as well as the behaviour of caretaking staff. The most serious problem they perceive within the provision of multidisciplinary care is the fact that they have not met any social worker or psychologist. Services of these two members of a multidisciplinary team have not even been offered to them. Many patients have told me that they were missing this kind of help, they were left to solve all problems by themselves.
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