The study is designed as a prospective clinical trial. Patients with histologically proven head and neck cancer treated by curative radiotherapy were included. The aim of this study was to investigate the relationship between pretreatment or posttreatment nutritional status and overall surival or locoregional / distant control. Pretreatment and posttreatment nutritional status was evaluated by body weight, body mass index, total serum protein, albumin, prealbumin, transferin and cholinesterase. Univariete and multivariete regression analyses were applied for prognostic factors associated with survival or tumor control. In this study we demonstrated, that poorer nutritional status prior curative radiotherapy, has a negative impact on subsequent control of cancer. The most sensitive parameter was serum cholinesterase. Serum cholinesterase  108 kat/l was the independent negative prognostic factor for both locoregional and distant tumor control. Results of this study indicate the need for intensive nutritional support before starting of curative treatment.

Head and neck squamous cell carcinomas (HNSCC) remain a significant cause of morbidity worldwide, with approximately 550,000 new cases diagnosed each year. The main etiological factors include smoking and alcohol consumption. The incidence of non-oropharyngeal HNSCC is gradually decreasing while the incidence of squamous cell oropharyngeal carcinoma (OPSCC) is still on the rise. This increasing incidence can be most likely attributed to an increasing prevalence of human papillomavirus (HPV) infection. From the clinical point of view the most significant fact is that patients with HPV positive OPSCC have better prognosis. HNSCC is linked to an alteration in the immune system. Only a limited number of studies have correlated both the immunological parameters and HPV status with patient prognosis. Therefore, we focused on the research of the immunological profile of patients with HNSCC of viral and non-viral etiology. In our study, 110 patients with HNSCC were enrolled. They were divided into HPV-positive and HPV-negative groups based on the expression of HPV 16 E6 mRNA detected in the tumor tissue. Basic lymphocyte subpopulations (CD3+, CD4+ CD25+ Treg, CD4+ CD25+ FoxP3 Treg, CD4+, CD8+, CD19, and CD3- CD16+ CD56+ cells) were determined by flow cytometry in the peripheral blood (PB). We observed...

A studies carries for the last twenty years accumulated data that show two different etiology of head and neck squamous cell carcinoma. Tumors located in the oral cavity are often independent of the viral infection and is associated with tobacco and alcohol use. Approximately 26 % of all HNC and more than 50 % of tonsillar cancers are associated with the presence of high risk human papillomavirus (HR HPV). The purpose of this study was to determine whether changes in HPV DNA prevalence in oral rinses and/ or HPV - specific antibody levels in sera of patients with head and neck carcinoma (HNC) have prognostic significance. Patients with HNC were enrolled (N=142). The presence of HPV DNA was assayed in tumor tissue and oral rinses, and HPV-specific antibodies were assessed in sera. Sera were drawn one month and one year after the end of treatment. One year after treatment, oral rinses were collected. Altogether, 59.2 % tumors were HPV positive. Initially, the presence of HPV DNA in the tumors strongly correlated with HPV DNA positivity in oral rinses as well as with the presence of HPV- specific antibodies in sera. Out of 66 patients with HPV positive oral rinses at enrollment, 84.8 % became negative at one-year follow up. The mean titres of HPV 16 E6 and E7 antibodies at follow- up were lower in...

Head and neck squamous cell carcinomas (HNSCC) remain a significant cause of morbidity worldwide, with approximately 550,000 new cases diagnosed each year. The main etiological factors include smoking and alcohol consumption. The incidence of non-oropharyngeal HNSCC is gradually decreasing while the incidence of squamous cell oropharyngeal carcinoma (OPSCC) is still on the rise. This increasing incidence can be most likely attributed to an increasing prevalence of human papillomavirus (HPV) infection. From the clinical point of view the most significant fact is that patients with HPV positive OPSCC have better prognosis. HNSCC is linked to an alteration in the immune system. Only a limited number of studies have correlated both the immunological parameters and HPV status with patient prognosis. Therefore, we focused on the research of the immunological profile of patients with HNSCC of viral and non-viral etiology. In our study, 110 patients with HNSCC were enrolled. They were divided into HPV-positive and HPV-negative groups based on the expression of HPV 16 E6 mRNA detected in the tumor tissue. Basic lymphocyte subpopulations (CD3+, CD4+ CD25+ Treg, CD4+ CD25+ FoxP3 Treg, CD4+, CD8+, CD19, and CD3- CD16+ CD56+ cells) were determined by flow cytometry in the peripheral blood (PB). We observed...

The introductory part of the diploma thesis primarily focuses on the history of radiotherapy, i.e. what it emerged from and how it developed, as it is one of the most important fields in medicine, especially because thousands of people are irradiated every day due to different tumour and non-tumour diseases. Another reason why ionizing radiation is described is the fact that it is a necessary part of tumour disease irradiation. Ionizing radiation is also connected with radiation protection. This section presents a historical overview of radiation protection, as well as principles and quantities of this field. Furthermore, it focuses on Czech acts, decrees, and government regulations which define various measures governing this issue. Radiation protection forms the basis of patient, workplace, and personnel monitoring. All this is connected with the measurement and evaluation of received personal doses. This brings the thesis to the field of dosimetry, therefore various dosimeters used in practice are described. The aim of this diploma thesis is the measurement of patients? personal doses in head and neck irradiation using the electronic personal dosimeter at the radiotherapy centre of Nemocnice České Budějovice, a. s. The thesis is based on the question of whether irradiation doses that patients with head and neck tumours receive outside the primary radiation beam are negligible. The theoretical part of the thesis uses all available resources from both foreign and Czech literature. The practical part is based on numerical statistics, i.e. a quantitative method. The research was carried out at the radiotherapy centre of Nemocnice České Budějovice, a. s. Irradiation of patients with head and neck tumours was performed on a linear accelerator. Each patient had a mask to which an electronic personal dosimeter was attached during irradiation. Using this dosimeter, it was possible to measure doses received outside the central radiation beam. The measured values were then used to carry out assessment using formulas. Patients who undergo cancer treatment receive relatively high doses of radiation, so my main goal was to measure personal dose equivalents at the reference point. When comparing the percentage of the number of examinations with the web portal Epidemiology of Malignant Tumours in the Czech Republic, it was found that irradiation of the neck is more frequent than irradiation of the head. The total values of personal dose equivalents are relatively high in each patient, but because it is medical treatment, these values are not subject to radiation exposure limits. The comparison of the irradiated areas shows that irradiation of the neck has small values of personal dose equivalents to 1Gy compared to irradiation of the head.

Head and neck cancers (HNSCC) are highly heterogeneous disease, results from two major carcinogens - tobacco and/or alcohol, or HR HPV infection. This thesis was based on 60 biopsies of head and neck tumours embedded into paraffin after histological verification. HPV infection, including particular types was monitored in different HNSCC regions by multiplex qPCR. Subsequent IHC demonstrated expression of p16INK4A and p53 as a possible diagnostic biomarker. Based on the information, patients with HNSCC can benefit from antiEGFR therapy by Cetuximab, but so far without defined predictors, the analysis of point mutations of Ras gene family (Kras, Nras) and Braf gene was performed. These mutations were monitored as potential predictive biomarkers, in correlation with gender, age and other risk factors. For all statistical processing the Chi-x2 test was used. Key words: Head and neck cancers, biopsy, HPV types, PCR, p16INK4A, p53, molecular predictors, Kras, Nras, Braf

Head and neck squamous cell carcinoma is the fifth most common cancer worldwide. They are associated with high morbidity and mortality. Despite considerable advances in surgical and oncological treatment over the past two decades, overall treatment outcome has only slightly improved. In my thesis I focused on serum gene expression analysis of head and neck cancer patients, which followed the tissue gene expression analysis in same patients. Further we investigated gene expression analysis in tumour stroma, which is now considered as significant factor in cancer initiation and progression. We revealed several candidate genes, which are involved in signalling pathways connected with cell differentiation and proliferation and are involved in apoptotic pathway (BCl-2, BCl-XL a MAX). As well we detected down-regulation of the main tumour suppressor p 53 protein. In peritumoural tissue we detected overexpression of cytokines typical for embryonal development and ectoderm differentiation - IGF-2 and BMP-4, which significantly influence the phenotype of normal keratinocytes. Further we identified several candidate genes relating with overexpression of Gal-1 in stromal myofibroblasts rich tissue (SPIN1, FUSIP1, TRIM23, SLC25A40, PTPLAD1, MP3K2). HNSCC is a heterogeneous disease despite the presence of...

The incidence of human papillomavirus (HPV) -associated oropharyngeal tumors is steadily increasing therefore, information about the prevalence of oral HPV and its risk factors is very important for future screening and early diagnosis of the disease. This thesis addresses three topics. The first topic is to evaluate the prevalence of oral HPV in a healthy population and to investigate risk factors for oral HPV infection, given that these data are almost completely absent in Central Europe. A statistically significantly higher rate of positivity (8.8%) of oral HPV infection was found in the group of older unvaccinated probands than in younger partially vaccinated volunteers (2.0%). The seropositivity rate of anamnestic HPV antibodies was comparable in both groups. None of the analyzed risk factors were significantly associated with oral HPV positivity. The second topic of the thesis is the dynamics of HPV specific antibodies in patients with head and neck cancer and their prognostic significance. In patients with cervical cancer, a decrease in HPV E6 / E7-specific antibodies is associated with a better prognosis. Another goal of the dissertation was to assess the importance of anamnestic antibodies and antibodies against oncoproteins E6 and E7 in long-term follow-up 2-14 years after the end of...

This thesis is focused on the epithelial mesenchymal interactions in tumors derived from squamous epithelium including tumors arising from minor cell population (melanocytes). This study is also reflecting aspects of epithelial glycobiology resp. the study of endogenous lectins, the galectins, in head and neck squamous carcinomas. Galectins represent, in the current concepts of cell and tumor biology molecules with a remarkable potential. Galectins participate, besides in regulation of pre- and postnatal homeostasis in normal tissues, also in many pathological processes such as autoimmune reactions or malignancies. In this thesis, we demonstrated the presence of galectin-1 and -2 and their glycoligands in interphasic and mitotic nuclei, which may contribute to regulation of the cell cycle. Furthermore, we demonstrated galectin-9 as a sensitive marker of transformation normal to the dysplastic squamous epithelium in head and neck. The epithelial mesenchymal interactions represent mechanisms, which are responsible for dynamic maintenance of the homeostasis of the organism during prenatal development, postnatal growth and during cyclic renewal of certain tissues. These interactions also participate in wound healing. On the other hand they play a crucial role in the process of tumor transformation,...

Papillomaviruses are small DNA viruses that are associated with the induction of epithelial tumors. HPV is an important infectious agent causing almost 100 % of cervical tumors but it can also cause tumors in other anogenital and head and neck locations in both men and women. Active HPV infection induces changes in miRNA expression that contribute to the tumor formation and progression. It is already known that papillomaviruses do not encode their own viral miRNAs but they affect the expression of cellular miRNAs. In my thesis I have in selected epithelial tumors (vulva, cervix, anus and tonsils) determined their etiology and analyzed the presence of miRNAs in tissues by next generation sequencing. From these data I determined the expression profiles of deregulated miRNAs in tumors relation to healthy tissues of corresponding location. Even though, sufficient number of samples was analyzed, it was not possible to detect HPV-core miRNA common to all analyzed HPV-induced tumors due to the absence of statistically relevant differentially expressed miRNAs in HPV positive vulvar tumors. Among the tumors of the other sites I found an overlap in three miRNAs. One of these miRNAs (miR-139-5p) and another one (miR-9-5p) which I have selected based on the study of other published data, were used for...