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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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New options for cervical cancer prevention
Adámková, Jana ; Kulhavá, Miluše (advisor) ; Fanta, Michael (referee)
This paper examines new ways of preventing cervical cancer. It adopts theoretical as well as empirical approach and is accordingly divided into two sections. The theoretical section provides a brief introduction to the anatomy and physiology of the uterus (Chapter 1.1) and then focuses on the disease itself (Chapter 1.2). The first three subchapters consider the disease incidence, the risk factors and the symptoms. The diagnostics are discussed in the fourth subchapter, which also provides a detailed description of Pap smear testing. Available treatments, currently consisting mainly of a surgical intervention, are examined in the subchapter on therapy. Lastly, the paper discusses ways of preventing cervical cancer, such as preventive gynecological exams and newly introduced vaccination against human papillomavirus (HPV); Silgard and Cervavix vaccines are examined in detail. The empirical section evaluates a questionnaire-based survey performed in a private gynecological practice. The aim of the survey was to map the awareness of cervical cancer preventive measures, especially the vaccine option, amongst different age groups of women and establish whether they are having their preventive gynecological tests done.
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Examination of HPV as part of cervical cancer prevention
PETŘÍKOVÁ, Petra
Sexually transmitted HPV infection (human papillomavirus), or infection with human papillomavirus, is a decisive factor in cervix carcinoma etiology. Human papillomaviruses are considered to be the most frequent sexually transmitted infection worldwide. In women, the life-long risk of infection is 80%. High-risk genotypes (high-risk HR HPV 16, HPV 18) were classified among carcinogens. The risk of cervix carcinoma in a woman who is HR HPV positive is 100 to 400 times higher compared to a woman who is HR HPV negative. The first part of my thesis contains a brief theoretical overview of HPV history, structure and classification. The next part deals with the ways of HPV transmission and the incubation period of the pathogenic agent in question. The incubation period as well as the replication cycle of the virus depend on the extent of infection and on the status of the immune system. Increased occurrence of papillomavirus infection is found in persons with a damaged component of cell immunity. In the further part of the thesis I focused on the diagnostic procedures and tests proving HPV infection including its clinical manifestations. Continued HPV infection, together with other relevant factors (smoking, immunodeficiency, lack of vitamins, stress, vaginal infection and hormone influence), increases the probability of cervix carcinoma occurrence. Here I also mention the histopathological classification, prognosis and treatment of these tumors. Considering the occurrence of cervix carcinoma, the situation in the CR is not as favorable as in other advanced countries where the screening is more effective. For comparison, the incidence and mortality in the CR are presented within global scale. Further on I attempted to stress the importance of primary prevention, mainly vaccination. The parts of secondary prevention mentioned in the thesis are preventive examinations, colposcopy, oncological cytology, serological methods and HPV test. The aim of my thesis is to emphasize the importance of testing for human papilloma virus HPV tests carried out in high risk group of women aged over 35 years within the system of preventive examinations. However, nowadays these examinations are accomplished just in women with an abnormal cytological finding. My thesis summarizes the quantitative findings as regards HPV tests done on the basis of determining the nucleic acid of human papillomaviruses by hybridization method with enhanced signal using chemiluminiscence detection. The detection of HPV was achieved with the use of the sets hc2 High-Risk HPV DNA Test and hc 2 HPV DNA Test from QIAGEN company. The thesis includes results of the tests for high-risk types of human papillomaviruses (HPV 16/18/31/33/35/39/45/51/52/56/58/59/68) found in 767 women over the period from January 1 2010 to December 31 2013. The tests were carried out at the Medical Microbiology Ward of the Hospital Jindřichův Hradec, a joint-stock company. The group of women with already positive cytological finding was divided into six age categories to highlight the high-risk groups of women over 35 and over 65. As I myself belong to the high-risk group over 35, my intention was to prove the hypothesis that the cause of the cytological changes in women over 35 can be attributed to the dangerous types of human papillomavirus. Finally, after carrying out the analysis of the obtained results, I attempted to propose a solution which could be used in practice.
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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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The evaluation of attitudes towards prevention of papillomaviruses infections in girls and women in České Budějovice and value of vaccination against papillomaviruses infections in students of ZSF JU.
FÜRSTOVÁ, Romana
Human papillomaviruses, also known in English as human papillomavirus, shortened HPV, are uncoated DNA viruses, called naked, that belong to the family Papoviridae. These are viruses which are known as small tumour viruses. Today, more than 100 types of human papillomaviruses are known, of which more than 40 infect the genital tract of men and women. Human papillomavirus is not only an agent of genital warts, which have been known and described in the medicine for two millennia, but also plays an important role in the development of cancer. Since the first thoughts about the relationship of viral infections and tumour, the development of knowledge came to the current view of HPV as an independent risk factor, particularly in the pathogenesis of cervical cancer. Papillomavirus types 16 and 18 play an important role in the pathogenesis of cervical cancer. Today, it has been scientifically proven that papillomavirus infection is a starting factor for cervical cancer. Cervical cancer is not only a serious health problem but also a medical and social one in Europe. It is the second most common cancer in women worldwide. HPV infection is currently the most common sexually transmitted disease. Up to 80 % of sexually active population meet HPV infection during their life, the highest prevalence rate of HPV is found in the age group of 18-25 years. Cervical cancer is a preventable disease after the development of a vaccine against HPV and introduced screening. The first, theoretical, part of the paper gives a comprehensive overview of various aspects of human papillomavirus infections based on the study of professional literature. In the second, research, part of my paper I focused on evaluating the approaches to the prevention of human papillomavirus infection as well as the cervical cancer in girls and women in České Budějovice and also the level of vaccination in students of the Faculty of Health and Social Studies against HPV. Based on the objectives of the paper hypotheses were drawn. Both objectives of the paper have been achieved.
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