The thesis is dedicated to the psychosocial aspects of women with breast cancer, such as stressful events, coping strategies, social support and personal and emotional factors and their possible specificity for this group of women. Aim of the theoretical part is a summary of the findings of type C personality, personality disposed to cancer and the overview of researches and particular results. The empirical part of the thesis is based on retrospective quantitative research with a focus on the number of stressful events, coping strategies, social support and features of alexithymia in women diagnosed with breast cancer (N = 70). These results were compared with a control group of women whose cancer have not been diagnosed (N = 81). The results show a significant difference in the amount of stressful events. Namely women with breast cancer have demonstrated significantly more stressful events prior to diagnosis than women without cancer. In addition, a significant difference has been found in the use of negative coping strategies which women without cancer experience using negative coping strategies more frequently than women with breast cancer. A significant difference has been found in the use of strategy "self-aggrandizement by comparison with others" which women with breast cancer use more than...

Drug resistance in cancer cells is a frequent cause of breast cancer therapy failure. The aim of this thesis was to elucidate mechanisms of resistance to taxanes, that are used in therapy of various types of cancer, including breast cancer. We particularly assessed the role of autophagy and changes in βII- and βIII isotype gene expression in development of taxane resistance. As model of breast cancer we used human sensitive cell lines SK-BR-3, MCF-7 a T47-D and resistant sublines SK-BR-3-PAC/REZ a MCF-7- PAC/REZ which grow in paclitaxel concentration lethal for sensitive sublines. In cell lines SK-BR-3 and MCF-7, taxane application decreased the level of autophagy, however in cell line T47-D led to its activation. We detected no difference between basal levels of autophagy in sensitive subline SK-BR-3 compared to resistant subline SK-BR-3-PAC/REZ, but we observed increased basal level of autophagy in sensitive subline MCF-7 compared to the resistant subline. Increase or decrease level of autophagy did not affect taxane resistance, except activation of autophagy in resistant subline SK-BR-3-PAC/REZ, that further increased the resistance to paclitaxel. Taxane application in cell line T47-D increased the levels of βII- and βIII-tubuline expression, however we did not find any similar effect in other tested...

Introduction: Breast cancer still remains the most common malignancy in women and its incidence is slowly increasing. A marked reduction of mortality has been achieved in the last 10 years thanks to modern diagnostic methods, mammary screening, and comprehensive and targeted cancer therapy. Modern diagnostic capabilities not only allow early diagnosis of a primary tumor lesion and precise determination of its biological nature before commencing treatment, but they also enable early diagnosis of local and regional recidives, including diagnosis of metastases in distant organs. In addition to clinical examination, conventional and complementary imaging examinations and tumor markers our objective was to determine the importance and use of growth factors in relation to the overall prognosis. The growth factors physiologically act already during the ontogenetic period when they control cell growth, proliferation, differentiation and apoptotic processes. It is known that they take part in the tumor growth processes which are characterized by autonomous behavior, increased proliferative activity, distinct differentiation activity and reduced apoptosis. Growth factors work as autoregulation factors in the neoplastic process as well as through their paracrine effects mediated by more or less specific receptors....

The screening mammography programme has been running succesfully in the Czech republic for 13 years. Due to its ability to uncover earlystages of breast cancer, it helps to fight this serious disease. Although the positive outcome of this programme in the Czech republic has been already proved, there is only approximately 50% of women who have been regularly treated with it.One of the major reasons for this fact is a fear of cancer induction caused by the use of X-rays during the mammography. The main goal of this thesis is to calculate the risk of breast cancer induction caused by the mammography and to compare benefits of the screening programme for a woman who goes for regular checkups and a woman who does not. The measurement of concrete doses was made in one screening centre center located in western bohemia region. The group of observed patients at the age of 45-59 was divided into three categories. The object of measurement was an average dose received during the screening mammography, plus an average dose received during an additional mammography, which may sometimes occure during the examination. These data was studied through a statistic investigation to prove that the received dose is not dependent on the patient´s age. In the theoretical part of this work main principals of the screening mammography programme and mammography itself are repeated. The methods of statistic investigation and the methodology for estimating breast cancer risks based on recommendations of ICRP Publication 103. In the practical part was proved, that the average dose received during the classical mammography does not depend on the age of the patient. This could not be proved for an additional mammography dose, because of not sufficient group of statistic data. The main hypothesis, that regular checkups using the mammographical screening programme is benefical for women , was verified.

The main concern of this thesis are breast, cervical and testicular cancer with focus on their epidemiology, screening and prevention. The epidemiological situation in Czechia and selected member states of EU is described by using indicators of incidence and mortality. The first main goal of this thesis is to analyze breast and cervical cancer screening coverage as well as the coverage by regular gynecologist check ups by using data from VZP health insurance company. It has been found that the breast cancer screening coverage rates are influenced by age structure. Cervical cancer screening coverage and gynecologist check-up coverage grow from 2009 to 2017. The other main task was to find out about knowledge of self-examination of Czech young people by using the data from questionnaires from educational programme "Healthy balls". Health knowledge among these students was low. There were found some differences in health behaviour and health literacy between gender and age groups.

BACKGROUND: The inactivation of the tumor suppressor gene BRCA1 is a predisposing factor for a breast/ovarian cancer development. Formation of cancer-specific alternative splicing variants with aberrant biological properties can represent additional mechanism decreasing the overall BRCA1 activity in DNA double strand break (DDSB) repair. In this study, we analyzed BRCA1 alternative splicing variants BRCA114-15 and 17-19 ascertained previously during the screening of high-risk breast cancer individuals. METHODS: We established a stable MCF-7 cell line-based model system for an in vitro analysis of BRCA1 variants. Using this system, we analyzed the impact of BRCA114-15 and 17-19 variants on DNA repair kinetics using comet assay and confocal immunomicroscopy. The capacity of DNA repair was assessed directly by an in vitro NHEJ assay and indirectly by a mitomycin C sensitivity test. The proliferation activities were determined by a clonogenic assay and growth curves. RESULTS: Overexpression of BRCA114-15 and 17-19 increases the endogenous level of DNA damage, slows down the DDSB repair, and decelerates the initial phase of radiation-induced foci formation and prolongs their persistence. Moreover, BRCA114-15 and 17-19 differentially influence the activity of HR and NHEJ and sensitivity of MCF-7 cells to ionizing...

Summary: Background: An increased risk for development of hereditary breast cancer is associated with germline mutations in BRCA1/2 and the influence of NBN mutations is also supposed. The aim of this study is to specify the frequency of recurrent mutations in BRCA1/2 in unselected breast cancer patients and the frequency of most common pathogenic mutations in NBN in Czech republic, to assess current criteria for genetic testing and to consider the addition of NBN to the tested genes. Methods: Screening for recurrent mutations 5382insC and 300T>G in BRCA1 was performed by RFLP, screening for mutations in exon 11 of BRCA1 was performed by PTT, screening for mutations in a selected region of exon 11 of BRCA2 by DHPLC, and screening for mutations in exon 6 of NBN by HRMA. All the mutations were confirmed by direct sequencing. Results: In 679 unselected breast cancer patients 7 carriers of 5382insC, 3 of 300T>G, and 4 of other mutations in BRCA1 were identified. 2 locally prevalent mutations were found in BRCA2. In 730 controls only one 5382insC BRCA1 mutation was identified. Out of 5 NBN mutations found in 600 high-risk patients two were 657del5 and one R215W. A total of 8 NBN mutation carriers were identified among 703 breast cancer patients, 2 of them 657del5 carriers and three R215W carriers. In 915...

ABSTRACT/SUMMARY Background: The clinical efficacy of tamoxifen therapy may be modified by the drug-metabolizing enzymes and transporting molecules involved into the pharmacokinetics of tamoxifen. The aim of this study was to evaluate the association of CYP2D6, ABCB1 polymorhisms and comedication with efficacy and safety of tamoxifen treatment. Methods: Totally 258 women with hormonal positive breast carcinoma were retrospectively evaluated in relation to CYP2D6, ABCB1 polymorphisms and comedication. Results: CYP2D6 polymorphisms or co-medication affecting CYP2D6 activity demonstrated no statistically significant effect on the efficacy of tamoxifen therapy or adverse event incidence; there was only a trend towards shortening the time to event (TTE) in CYP2D6 poor metabolizers. ABCB1 polymorphism rs2032582 was not associated with clinical outcomes, while a trend towards an increase of TTE in variant allele carriers was noted. The ABCB1 polymorphism rs1045642 demonstrated statistical significance in premenopausal patients (p = 0.0012, HR 0.69 (95% CI 0.21 to 2.31), and its significant association was noted with gynaecological /vasomotor adverse events (p = 0.0221, HR = 1.0588), with no evidence of the influence on the incidence and onset of venous complications. Conclusions: Although this work did not show...

Professional treatises and articles in commercial media having breast carcinoma in the heading characterize it mostly as an epidemiologically serious phenomenon. This fact cannot be doubted regarding to occurrence of this carcinoma disorder of women (in minimal cases of men). At present the patients become co-coordinators of the treatment in far bigger rate than they used to. Studies and practical experience in this context show that only quantitative aspects of life like the length are not the determined ones for the patient, but more and more patients prefer quality of the survival. Traditional medicine under the pressure of such findings tends to modify treatment procedures in relation with keeping certain quality of life of oncological patients. That is the reason why traditional medicine in the objectives of psychooncology specialization maps the rate of such level, searches preferences of the patients in context of type of the carcinoma, the stage of the disease, individual emotional attitudes etc. Psychooncology becomes an equal partner to radiology, surgery, pathology, oncology and psychology itself in terms of help patients. The possibility to provide psychooncological investigation in the centre of diagnosis and treatment of breast carcinoma of women Mamografie Nemocnice Písek a.s. and to process the data by the form of diploma work seemed purposeful in this case. In the theoretical part initial conditions of breast carcinoma by traditional medicine were defined {--} diagnosis, cure and consecutive treatment. Common emotional maps while facing cancer diagnosis were defined. Methods of determination quality of life of patients in historical and contemporary trends were mentioned. The selected methodology was described by the form of partially anonymous questionnaires and investigative file of 128 women was characterized. The aim of this work was to search the women with diagnosis of breast carcinoma and development of their partnerships, relationships in extended family, inter - personal relationships at work and to compare quantifiable parameters with the time before setting the diagnosis. Mapping somatic (tiredness, pain, insomnia, digestive problems) and psychosomatic factors determining quality of life of sick women was the major axis of searching and investigation. These aims were applied to defined hypotheses which dealt with goals mentioned in the context of contemporary state of comprehension to help people with oncological diagnosis: breast carcinoma is not only serious somatic problem but also psychosocial issue although psychooncology is not the specialization systematically incorporated into the complex oncological solution of patients at the moment. Dates result in the fact that the factors which contribute most to the quality of life concerning to somatic influences are negatively felt tiredness followed by pain afterwards. The dominant psychical influences include depression, anxiety and insomnia. In psychosocial sphere social support is unambiguously dominantly important for quality of life and according to the literature it can contribute even to the length of survival. Following the data, lucid absence of psychooncological help in early stages after detected disorder and during contingent recovery seemed insufficient. The diploma work was not purposeless. There was a deep interest and support of all medical staff of the mammography centre. If we succeed to include psychooncological intervention into a set of conditions asserted in the horizon of treatment of breast cancer, then the data will daily contribute to help of sick women. By generalization it is possible to outline the way in understanding the complex treatment and solving further oncological diagnoses and procedures.

(EN) Tumours are heterogeneous and consist of multiple populations of cells. The population of cells with tumour-initiating capability is known as cancer stem cells (CSC). Cells with increased stemness properties and elevated resistance to anti-cancer treatment have been shown to be highly affected upon decline of mitochondrial respiration, linking the concept of CSCs to deregulated bioenergetics. Consistently, functional electron transport chain (ETC) is crucial in tumorigenesis. Expression of HER2 oncogene, associated with resistance to treatment in breast cancer, has been connected with regulation of mitochondrial function. We therefore investigated the possibility that manipulation of mitochondrial bioenergetics via disruption of ETC eliminates the conventional therapy-resistant populations of tumour, such as CSCs and HER2high cells. We demonstrate that HER2high cells and tumours have increased complex I-driven respiration and increased assembly of respiratory supercomplexes (SC). These cells are highly sensitive to MitoTam, a novel mitochondria-targeted derivative of tamoxifen, acting as a CI inhibitor and SC disruptor. MitoTam was able to overcome resistance to tamoxifen, and to reduce the metastatic potential of HER2high cells. Higher sensitivity of HER2high cells to MitoTam is dependent on...