Structured abstract Hypothesis Cancer stem cells (CSCs) are subpopulations of cells which could contribute to tumor growth, metastasis formation and chemoresistance. CSCs can be detected by surface markers assessed by immunohistochemistry methods. A typical surface marker for CSCs is CD44 (standard form). We assumed, that CD44(s) could serve as a prognostic factor and marker of chemoresistance in patients with epithelial ovarian cancer. The aim of study 1. To recruit group of patients with histologically verified epithelial ovarian carcinoma. 2. To evaluate prognostic significance of known prognostic factors in our series of patients. 3. To assess the expression of CD44 in specimens of primary tumors and specimens of implantation metastasis using immnunohistochemistry and analyze their correlation. 4. To evaluate the expression of CD44 in relation to known prognostic factors. To analyze the significance of CD44 expression evaluation for overall survival, disease-free interval and chemoresistance. To find CD44 positivity cut-off by using statistical methods Materials and Methods A retrospective study was performed on 87 patients with histologically verified EOC. All patients were tested for primary tumor specimens, 48 of them were tested with regard to both specimens of primary tumor and implantation...

Lung cancer is the leading cause of cancer mortality worldwide. Understanding biological processes of specific antitumor immune response remains of an eminent interest and represents necessity for designing successful antitumor immunotherapeutic strategies. The theoretical part of the thesis describes components of the immune system that are involved in antitumor response and discusses their role in the hitherto known and used lung cancer immunotherapy. In the practical part of the thesis, two studies studying different aspects of anticancer immune response are described. Both studies were conducted in cooperation with 3rd Surgical Department 1st Faculty of Medicine, Charles University and University Hospital Motol and with the biotechnology company Sotio a.s. The first study is focused on the humoral component of the specific antitumor response and prospectively analyses serum frequency of antitumor antibodies against NY-ESO-1, Her2/neu and MAGE-A4 antigens in 121 patients with NSCLC. Here it was shown for the first time that tobacco smoking significantly increases the frequency of NY- ESO-1 antibodies in sera of smokers in comparison to ex-smokers and non-smokers. The second study is focused on the cellular component of the specific antitumor response investigating the activity of the dendritic...

Summary: Breast cancer (BC) is the most frequent cancer type in female population of Europe. Approximately 5 - 10 % accounts for its hereditary form which is characterized by high penetrance, early onset, risen recurrence risk and development of other cancers. Mutational analyses of high risk patients identify a predisposing mutation in one of the most studied genes (BRCA1, BRCA2, TP53, ATM, CHEK2, NBS1, PALB2) only in less than one third of tested breast cancer patients. Lately, with the use of new methods of next-generation sequencing, a number of other susceptibility or candidate genes were characterized, but the incidence of their pathogenic alteration is often geographically different. A notable proportion of high risk patients from families with hereditary BC can represent carriers of population-specific, or private mutations. Most of the to date identified BC susceptibility genes codes for proteins involved in DNA repair, especially repair of double strand break DNA repair. Nevertheless the mutation analysis was conducted only on a small fraction of these DNA repair genes. We can expect that in the group of yet nontested genes coding for DNA repair proteins a rare, but clinically important genetic alterations predisposing to BC in affected families can be discovered. This work describes a...

Introduction: The aim of this study was to evaluate the role of genetic and lifestyle factors in the risk of onset and progression of colorectal and pancreatic cancer. The first part deals with the etiological factors and the importance of polymorphisms in biotransformation enzymes and genetic alterations in the gene CHEK2 in the origin of these malignancies. In the second part, the ABC transporter genes were analyzed as potential prognostic and predictive markers of a treatment's outcome. Materials and methods: The polymorphisms and other genetic alterations were detected using real-time PCR, allelespecific PCR and PCR-RFLP methods in DNA which was extracted from the blood of patients. The frequency of polymorphisms was evaluated and their importance was assessed with regard to the available epidemiological data. Gene expressions were determined by qPCR in paired samples of tumor tissue and adjacent non-tumorous parenchyma. Results: A majority of the observed polymorphisms failed to show a relationship between their presence and the risk of any of these malignancies. CYP2A13 variant allele*7 coding inactive enzyme was found in 7 of 265 controls and in none of 235 pancreatic carcinoma patients. In contrast, GSTP1-codon 105 Val variant allele and GSTT1-null genotype were associated with an elevated...

Background: More than 90 % of anal cancers are caused by high-risk human papillomavirus (HR HPV) infection and a history of cervical intraepithelial neoplasia (CIN) and cervical cancer is established as possible risk factor. The aim of this study was to demonstrate relationship between anal and cervical HPV infection in women with different grades of CIN and microinvasive cervical cancer and to determinate potential risk factors for concurrent cervical-anal HPV infection. Methods: A total of 272 women were enrolled in the study. The study group included 172 women who underwent conization for high-grade CIN or microinvasive cervical cancer. The control group consisted of 100 women with non-neoplastic gynecologic diseases or biopsy- confirmed CIN 1. All participants completed a questionnaire detailing their medical history and sexual risk factors and were subjected to anal and cervical HPV genotyping using Lynear array test (Roche). Results: Cervical, anal, and concurrent cervical-anal HPV infections were detected in 82.6 %, 48.3 % and 42.4 % of women in the study group, and in 28.0 %, 26.0 % and 8.0 % of women in the control group, respectively. The prevalence of the HR HPV genotypes was higher in the study group and significantly increased with the severity of cervical lesion. Concurrent infections...

This diploma thesis deals with the topic of hidden malnutrition in patients with advanced stage of ovarian carcinoma. Tumor diseases are often accompanied by malnutrition. In the case of ovarian cancer, malnutrition may be hidden, primarily due to ascites, which can distort body weight. Out of the patients included in this study 32 % had ascites. The basic nutritional status test in hospitals is the nutritional screening performed on each hospitalized patient to detect the risk of malnutrition. Other methods such as anthropometric measurements, laboratory values, bioimpedance analysis, or less commonly, imaging processes can also be used to detect malnutrition. The aim of this thesis was to evaluate whether nutritional screening and regular weight control in patients with advanced ovarian cancer is sufficient to diagnose malnutrition. The results have shown that the inclusion of anthropometric measurements between routine screening can be beneficial in detecting a greater number of malnourished patients. Also shifting the BMI threshold in nutritional screening for patients over 65 would greatly increase the capture of patients at risk of malnutrition. The secondary focus was to find whether the presence of ascites can be a determining factor in malnutrition being left undiagnosed, and which simple...

In worldwide basis, the carcinoma of cervix is the second most frequent malignant tumour in women. There is up to 1200 new cases diagnosed in our country every year. Considering the sad fact that more than 400 women die in our country every year, the battle against the carcinoma of cervix became recently one of the priorities of the Ministry of Health of the Czech Republic. The nationwide screening focused on early detection of cervical cancer was launched in our country in 2008. The dissertation paper entitled ``Awareness of university students of the risk of cervical cancer and its prevention`` is mainly focused on monitoring of awareness of university students of the risk of cervical cancer disease and the possible ways of its prevention. The assessed group was made of university students, young women from South Bohemian and Prague universities. In the research part of the dissertation the author used a method of questioning with the technique of data collection using anonymous questionnaire. The research has revealed that the students have basic knowledge on the issue of cervical carcinoma, namely in the area of risk and prevention. It was also found that the awareness of the students of the South Region on this issue was much better than of the students in the Prague region. Despite the overall positive results, the research shows the need to inform the public especially about the hazards of smoking as a possible risk factor associated with cancer. It is also necessary to expand knowledge of women in already developed symptoms of the disease. There is currently only one known - bleeding after intercourse. In the area of prevention it is also desirable to highlight the availability of some special examinations for men, while appealing to the possibility of lifelong disability as a serious consequence of this disease. Research shows that it is still necessary to inform more and better the public about this issue. From the views of the respondents it is clear that in addition to ads aimed at promoting vaccination, the problems of the disease is poorly presented. This is confirmed by the fact that students do not know any organization focused on this problem. To a good awareness of women in this field, in terms of risks, prevention and possible vaccination, should contribute especially gynaecologists, together with the midwives, because as part of the preventive visits they have the opportunity to address the women and to specifically discuss the issues with them. It is unfortunately evident from the research that these doctors inform minimally about the possible ways of prevention. In my opinion, to respond to the observed facts and to refine and improve the information system for a maximum possible way it is in the interests of all women and girls, whether by improving the own work of gynaecologists, as well as improving awareness about this problem through the media or by using a variety of booklets and leaflets in offices of other physicians, that are currently seen only sporadically.

No description available.

Breast cancer is the most frequent malignant disease in the female population worldvide. About 10 % of all cases are of hereditary origin. The inactivation of tumor suppressor gene BRCA1 is the main genetic predisposing factor in breast cancer in the Czech Republic. Primarily, BRCA1 participates in DNA double strand break repair. Depending on cell cycle phase, the damage is repaired by homologous recombination or non-homologous end joining. Alternative splicing variants of BRCA1 are frequently detected during the genetic screening of high risk patients. The clinical significance of these variants is unknown. Understanding of the nature of breast cancer genetics is the critical factor for early diagnosis. Based on earlier studies from the Institute of Biochemistry and Experimental Oncology 1st Faculty of Medicine Charles University, two alternative splicing variants which were repeatedly detected in patients, were chosen for functional analysis. The aim of this work is to investigate the impact of alternative splicing variants BRCA1Δ5 and BRCA1Δ10 on DNA double strand breaks repair. Particular variants were over- expressed in the cells of model system. Activity of homologous recombination (HR) and non-homologous end joining (NHEJ) was scored by in vitro DNA repair assay. The cellular localization of...

The immunotherapeutic drug DCVAC/OvCa is being tested in the treatment of ovarian cancer patients within the SOV02 clinical trial (Eudra CT number: 2013-001323-38). Ovarian cancer belongs to gynaecological malignancies with the highest mortality rate. Around 60% of patients are diagnosed at advanced stages. Despite the initial successful treatment, relapses occur in most cases, and the disease often becomes resistant to chemotherapy. Effective therapy for relapsed or metastatic patients is still missing. The solution could be immunotherapeutic treatment. DCVAC is an active cellular immunotherapy based on autologous dendritic cells. The aim of this diploma thesis was monitoring of immune parameters in samples from clinical trial SOV02 patients during the time period defined in the study protocol. We have monitored the presence of antigen specific T lymphocytes, tumor specific antibodies, immunosuppressive populations of regulatory T cells and MDSC cells, and also the expression of inhibitory molecules on the surface of T lymphocytes. We observed higher levels of Her-2, Muc-1 and MAGE-A1 antibodies in the DCVAC/OvCa treated group of patients versus the control group. Significant differences in the other monitored parameters were not observed. However, a large amount of data have been obtained that...