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Mechanisms of papillomavirus genome integration into the human chromosome
Frčková, Tereza ; Šmahelová, Jana (advisor) ; Fraiberk, Martin (referee)
Human papillomaviruses (HPV) are small non-enveloped DNA viruses that can cause malignancies in the human population. They are often associated with carcinomas in anogenital area in both men and women, but also with part of head and neck cancer. In infected cells, the HPV genome is present as a circular molecule of DNA, called an episom. Certain circumstances result into the occurrence of a linearization of the HPV genome and a subsequent integration in the human chromosome. The integration plays a role in the cell behavior and contributes to immortalization and tumor transformation. The HPV genome integration is influenced by various viral or cell factors that affect the HPV genome stability in the cell. Interaction between viral and cell protein can often lead to activation of DNA damage response, that virus exploits for replication of viral genome. Viral genome integration is also more likely to occur in certain HPV types. Another factor is the area of infection, where the neoplastic progression was studied.
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Plant virus-based biotechnology
Vaculík, Petr
The latest model of tertiary structure of capsid protein of potato virus X (PVX CP) was used as a template to design new insertion sites suitable for the preparation of PVX-based antigen presentation system. Based on this model, seven insertion sites (A-G) located in putative surface loops were tested. As an antigen inserted into these sites was used 17 amino acids long epitope derived from human papillomavirus type 16 E7 oncoprotein (E7 epitope) fused with either 6xHis tag or StrepII tag in both possible orientations (6xHis-E7 and E7-6xHis, StrepII-E7 and E7-StrepII). Prior to plant expression, modified PVX CPs were expressed in Escherichia coli MC1061. The results showed that only PVX CP carrying StrepII-E7 or E7-StrepII in the insertion site A formed virus particles. The results from transient expression experiments with modified PVX CPs in Nicotiana benthamiana showed that only the insertion site A (located between 24th and 25th amino acid in the PVX CP) could tolerate all tested inserts. Importantly, viral particles were detected only in the presence of StrepII tag and their stability was affected by the insert orientation (StrepII-E7 vs. E7-StrepII) as only the viral particles presenting E7-StrepII could be purified. Besides the preparation of PVX-based antigen presentation system, an...
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Knowledge and attitudes to HPV immunisation IV
Jelínková, Tereza ; Zimčíková, Eva (advisor) ; Kolmanová, Eliška (referee)
Knowledge and attitudes to HPV immunisation IV Author: Tereza Jelínková Thesis supervisor: PharmDr. Eva Zimčíková, Ph.D. Introduction HPV infection is one of the most common sexually transmitted diseases causing, apart from genital warts, other malignancies, most often cervical cancer. The most effective way of prevention is vaccination. So far, there have been 3 types of vaccines, most recent one being the nonavalent vaccine providing up to 90 % protection against cervical cancer- causing HPV, in contrast to the previously available 70 % protection from bivalent or quadrivalent vaccines. Aims The main aim of this thesis was to investigate the knowledge and attitudes towards vaccination against HPV, and knowledge about HPV in general, among secondary school students. Furthermore, to determine their vaccination status and compare the findings with data from previous theses, including a comparison of their knowledge about HPV and relevant prevention. Methodology The data was obtained by means of a questionnaire survey, which took place at three secondary schools. In December 2017 at Gymnázium in Mladá Boleslav, then during June 2018 at Gymnázium in Brandýs nad Labem, and finally in September 2018 at Gymnázium Chotěboř. The obtained data was recorded in a Microsoft Excel spreadsheet and then...
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Impact of pattern and functional properties of tumor-infiltrating immune cells for clinical outcome of head and neck cancer
Hladíková, Kamila ; Špíšek, Radek (advisor) ; Plzák, Jan (referee) ; Reiniš, Milan (referee)
Head and neck squamous cell carcinoma encompasses a complex and heterogeneous group of malignant diseases. Originally, this tumor type was associated with tobacco and alcohol consumption. However, a significantly expanding subset of tumors associated with oncogenic human papillomavirus infection arising in deep tonsillar crypts was identified within the last decades. Due to the essential role of the immune system in antiviral and anticancer immune response, the prognosis of patients is significantly influenced by the volume, composition and functional capacity of the immune infiltrate. The immunosuppressive landscape of head and neck cancer leads to unfavorable outcome of patients and decreased efficacy of immunotherapy. The response rate to standard treatment is high, however, standard therapy is accompanied by considerable toxicity influencing the quality of life. In 2016, the first immunotherapeutics for the treatment of patients with recurrent squamous cell carcinoma of the head and neck were approved - the anti-PD-1 immune checkpoint inhibitors nivolumab and pembrolizumab. This type of therapy, based on mitigation of immunosuppression, shows strong efficacy and less toxicity in combination with other therapies. Therefore, anti-PD-1 immunotherapy was recently approved in the first-line...
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The use of IHC marker p16 in HPV lesions of the cervix
ILOVIČNÁ, Kristýna
HPV is one of the most common sexually transmitted diseases. It mostly spreads by sexual way, less often orally, by contaminated fingers or by beddings. Another ways of transmission are from the mother to the fetus at birth or transplacentarly. It usually occurs in young women aged 20 to 25 years and approximately 80% of sexually active individuals have experience with it during their life. Human papillomavirus is an infectious agent associated with a specific type of human cancer and it occurs in 99,7 % of all cervical cancers. More than one hundred papillomaviruses have been identified so far, we can divided them into the lowrisk and the highrisk groups. One of the best possible ways to reduce the risk of a disease is to keep a sexual relationship with only one partner. But the partner can also be carrier of the infection without revealing any symptoms. Preventive measures also include regular gynecologycal examinations. The incidence of cervical cancer has significantly decreased in many developed countries, mainly due to cytological screening programmes. The disease could be detected in the early stages, when the possibilities of successful treatment are noticeably higher. There are three standard procedures in the treatment of cervical cancer - surgery, radiotherapy and chemotherapy. In the practical part, I compare the positivity of the p16 marker between each histological groups by using light microscope NIKON Eclipse E400. The use of p16 immunohistochmically stained tissue improves total diagnostic accuracy. In this way 173 samples were examined at the Departement of Pathology Nemocnice Písek a.s. during years 2016 and 2017. We divided them, according to stage of severity, into 34 low-grade lesions and 139 highrisk lesions. 18 of the lowrisk lesions and 130 highgrade lesions expressed p16 positivity. Staining of remaining slides was negative.
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Plant virus-based biotechnology
Vaculík, Petr ; Čeřovská, Noemi (advisor) ; Ryšánek, Pavel (referee) ; Petrzik, Karel (referee)
The latest model of tertiary structure of capsid protein of potato virus X (PVX CP) was used as a template to design new insertion sites suitable for the preparation of PVX-based antigen presentation system. Based on this model, seven insertion sites (A-G) located in putative surface loops were tested. As an antigen inserted into these sites was used 17 amino acids long epitope derived from human papillomavirus type 16 E7 oncoprotein (E7 epitope) fused with either 6xHis tag or StrepII tag in both possible orientations (6xHis-E7 and E7-6xHis, StrepII-E7 and E7-StrepII). Prior to plant expression, modified PVX CPs were expressed in Escherichia coli MC1061. The results showed that only PVX CP carrying StrepII-E7 or E7-StrepII in the insertion site A formed virus particles. The results from transient expression experiments with modified PVX CPs in Nicotiana benthamiana showed that only the insertion site A (located between 24th and 25th amino acid in the PVX CP) could tolerate all tested inserts. Importantly, viral particles were detected only in the presence of StrepII tag and their stability was affected by the insert orientation (StrepII-E7 vs. E7-StrepII) as only the viral particles presenting E7-StrepII could be purified. Besides the preparation of PVX-based antigen presentation system, an...
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Plant virus-based biotechnology
Vaculík, Petr
The latest model of tertiary structure of capsid protein of potato virus X (PVX CP) was used as a template to design new insertion sites suitable for the preparation of PVX-based antigen presentation system. Based on this model, seven insertion sites (A-G) located in putative surface loops were tested. As an antigen inserted into these sites was used 17 amino acids long epitope derived from human papillomavirus type 16 E7 oncoprotein (E7 epitope) fused with either 6xHis tag or StrepII tag in both possible orientations (6xHis-E7 and E7-6xHis, StrepII-E7 and E7-StrepII). Prior to plant expression, modified PVX CPs were expressed in Escherichia coli MC1061. The results showed that only PVX CP carrying StrepII-E7 or E7-StrepII in the insertion site A formed virus particles. The results from transient expression experiments with modified PVX CPs in Nicotiana benthamiana showed that only the insertion site A (located between 24th and 25th amino acid in the PVX CP) could tolerate all tested inserts. Importantly, viral particles were detected only in the presence of StrepII tag and their stability was affected by the insert orientation (StrepII-E7 vs. E7-StrepII) as only the viral particles presenting E7-StrepII could be purified. Besides the preparation of PVX-based antigen presentation system, an...
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Molecular mechanisms of carcinogenesis induced by HPV from Alpha and Betapapillomaviridae
Pokrývková, Barbora ; Tachezy, Ruth (advisor) ; Dvořáček, Lukáš (referee)
Human papillomaviruses (HPV) are small DNA viruses ubiquitously present in population. They infect mucosal and cutaneous epithelium and cause benign and malignant diseases. Research of HPV became more intensive after 1983, when these viruses were isolated for the first time from cervical carcinoma samples. Nowaday it is known, that number of other malignancies is associated with HR HPV infection and the research is focused on evaluating the role of these viruses in skin cancer. This bachelor thesis outlines mechanisms by which HPV from Alfa and Betapapillomaviridae genus causes malignant and benign lesions. The main HPV oncoprotein is protein E6, which binds p53 and targets it for degradation, and protein E7 which interacts with retinoblastoma protein and influences his function in cell cycle regulation. Papillomaviruses from genus alpha contain additionally E5 oncoprotein which is not present in viruses from genus beta. This suggests that the mechanisms of cancerogenesis initiated by viruses from these two genera will be different. Powered by TCPDF (www.tcpdf.org)
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HOW EDUCATION AFFECTS WOMEN IN THE VYSOČINA REGION TO USE A POSSIBILITY OF CERVICAL CANCER VACCINATION
ŠIDLÁKOVÁ, Lenka
The bachelor´s work captures a level of knowledge of present-day girls and young women about cervical cancer. It shows their attitude towards the possibility of cervical cancer vaccination, if they know the fees, a number of doses, risk factors etc. The work is divided into two parts, a theoretical and a practical ones. The theoretical part describes the current status-the anatomy of female reproductive organs, the history, occurence, causes, transmission, symptoms, diagnoses, possibilities of treatment and mainly prevention. The practical part contains targets and hypotheses, methods, results of the research that are transferred into the graphs. The practical part also includes a discussion where the results, obtained through my own research, are thought about. The results are further compared with similar conclusions of other authors. All is completed by my own opinion.
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