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The Role of Genetic Mutations in Breast Cancer
Šustr, Jan ; Fínek, Jindřich (advisor) ; Petráková, Katarína (referee) ; Prausová, Jana (referee)
Introduction: About 5 - 10% of breast carcinomas are caused by genetic mutations. The most common genetic mutation that is involved in the development of this malignancy is a mutation in the tumor suppressor genes BRCA1/2 whose carriers have approximately a 70% lifetime risk of developing breast cancer. The prognosis of patients with BRCA1/2-asociated breast carcinoma, compared to patients with sporadic breast carcinoma is the subject of many studies with ambiguous results. Aim: The aim of the theoretical part of this work was to approach the issue of breast cancer and the most common genetic syndromes associated with it. In the practical part of this work a retrospective study was carried out in order to compare BRCA1/2 mutated breast cancer patients with non-mutated breast cancer patients in the tumor profile, methods of treatment and prognosis. Methods: We retrospectively analyzed the data of 134 patients who were tested for the presence of BRCA1/2 mutation at the Institute of Medical Genetics, University Hospital in Pilsen during the years 2013-2018 and at the same time were treated for early breast cancer at the University Hospital in Pilsen during the years 2000-2020. 32 patients were BRCA1 positive (24%), 10 BRCA2 positive (7%) and 92 without BRCA1/2 mutation (69%). The follow- up time was...
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The prevalence of anal HPV infection in women with high grade cervical intraepithelial neoplasia and its relation to sexual behavior
Sehnal, Borek ; Sláma, Jiří (advisor) ; Bouda, Jiří (referee) ; Prausová, Jana (referee)
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...
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Polymeric-drug Conjugates in Treatment of Head and Neck Squamous Cell Carcinoma
Betka, Jaroslav ; Říhová, Blanka (advisor) ; Prausová, Jana (referee) ; Reiniš, Milan (referee)
Malignant diseases are after cardiovascular diseases the second most common cause of death in the developed countries. The number of patients newly diagnosed with cancer is constantly rising, on average by 2.5% yearly. This trend also applies to squamous cell carcinoma of the head and neck, which is the sixth most common oncological disease. Its occurrence is most influenced by two external risk factors: smoking and abuse of alcohol; latest research indicates that for the emergence of neoplasia is crucial not only the amount of and duration of the use of a harmful substance but also the time of day when a harmful substance is used as well as psychological dependence on the substance. But recently, we are witnessing growth of the frequency of occurrence of the squamous cell carcinoma of the pharynx with non-smokers and younger age groups in connection with presence of the HPV infection in tumor. The forms of so far most commonly used anticancer therapy (surgery, radiotherapy, chemotherapy) have, despite progressions over the last decades, lead to significant improvement only with some types of cancer but in the case of squamous cell carcinoma of the head and neck is the total probability of five-year survival still low, approximately 40%. Therefore we are turning our attention to the new forms of...
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Analysis of prognostic features in patients with breast cancer and colorectal cancer.
Vočka, Michal ; Petruželka, Luboš (advisor) ; Fínek, Jindřich (referee) ; Prausová, Jana (referee)
Cancers represent second the most common cause of death in the Czech Republic. The most common are breast and colorectal cancers. Identification of prognostic factors improving decision-making approaches for treatment optimization belongs to the key aims of clinical research in oncology. Carriers of mutation in cancer-susceptibility genes represent a small but clinically important group of high-risk patients. The implementation of NGS have accelerated predisposing genes analyses. The large extent of data about the presence of variants in predisposing genes is in striking contrast to only a very limited information available about clinico-pathological characteristics of mutation carriers. Determination of the risk of tumor development in carriers of rare mutations or variants of unclear significance in genes with incomplete penetrance represent substantial drawbacks of current NGS analyses. To address these issues, we have attempted i) to introduce a unified approach to NGS analysis in breast cancer patients, ii) to characterize importance of prognostic factors in BRCA1/BRCA2 mutation carriers, and iii) to identify the cancer risks in carriers of germline mutations in the CHEK2 gene. Colorectal cancer represents seemingly histologically homogeneous disease. However, at the molecular level it can be...
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Polymeric-drug Conjugates in Treatment of Head and Neck Squamous Cell Carcinoma
Betka, Jaroslav ; Říhová, Blanka (advisor) ; Prausová, Jana (referee) ; Reiniš, Milan (referee)
Malignant diseases are after cardiovascular diseases the second most common cause of death in the developed countries. The number of patients newly diagnosed with cancer is constantly rising, on average by 2.5% yearly. This trend also applies to squamous cell carcinoma of the head and neck, which is the sixth most common oncological disease. Its occurrence is most influenced by two external risk factors: smoking and abuse of alcohol; latest research indicates that for the emergence of neoplasia is crucial not only the amount of and duration of the use of a harmful substance but also the time of day when a harmful substance is used as well as psychological dependence on the substance. But recently, we are witnessing growth of the frequency of occurrence of the squamous cell carcinoma of the pharynx with non-smokers and younger age groups in connection with presence of the HPV infection in tumor. The forms of so far most commonly used anticancer therapy (surgery, radiotherapy, chemotherapy) have, despite progressions over the last decades, lead to significant improvement only with some types of cancer but in the case of squamous cell carcinoma of the head and neck is the total probability of five-year survival still low, approximately 40%. Therefore we are turning our attention to the new forms of...
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Metallothioneins and other biomarkers in the treatment decision in pediatric cancer patients
Kruseová, Jarmila ; Eckschlager, Tomáš (advisor) ; Prausová, Jana (referee) ; Raudenská, Martina (referee)
Metallothioneins (MT) are low molecular weight, cysteine-rich proteins maintaining metal ions homeostasis. They play a role in carcinogenesis and may also cause chemoresistance. The aim: was to explore the relationship between MT serum levels in children suffering from malignant tumours and correlate with laboratory findings during anticancer treatment. Material and methods: This prospective study involves 865 samples from 172 patients (71 girls and 101 boys) with malignant tumours treated from 2008 to 2011. Patient median age: 9.9 years (0.1-19.5). Metastatic diseases at diagnosis: 93 patients (54.1%), reccurence: 12(7%), died: 32(18.6%). MT serum levels were determined using differential pulse voltammetry-Brdicka reaction. Results: Mean MT level 2.67 uM/l was five times higher that of control group (0.05). No significant difference between MT levels in different tumours. No correlation between MT levels in active disease and disease in remission (p =0.33). However, we found a positive correlation between MT levels and age (p=0.009), negative correlation between MT and creatinine (p=0.003). Patients who had disease recurrence had lower MT levels during the treatment (remission 2.67 vs. recurrence 2.34, p=0.001) Conclusion: Patients who had early disease recurrence had lower MT levels during treatment...
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The prevalence of anal HPV infection in women with high grade cervical intraepithelial neoplasia and its relation to sexual behavior
Sehnal, Borek ; Sláma, Jiří (advisor) ; Bouda, Jiří (referee) ; Prausová, Jana (referee)
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...
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The role of the immune system in colorectal and ovarian cancer
Kocián, Petr ; Hoch, Jiří (advisor) ; Prausová, Jana (referee) ; Žaloudík, Jan (referee)
Prediction of clinical outcome in cancer is usually achieved by histopathological evaluation of tissue samples obtained during surgical resection of the primary tumor. Traditional tumor staging (AJCC/UICC-TNM classification) summarizes data on tumor burden (T), presence of cancer cells in draining and regional lymph nodes (N) and evidence for metastases (M). However, it is now recognized that clinical outcome cansignificantly vary among patients within the same stage. Data collected from largecohorts of human cancers has demonstrated the impact of immune-classification, which has a prognostic value that may add largely to the significance of the AJCC/UICC TNM-classification. In our study we examined the immune cells that infiltrated the tumor tissues of colorectal and ovarian cancer patients. In a cohort of newly diagnosed colorectal cancer patients we examined the correlations between the KRAS mutational status, patterns of tumor-infiltrating immune cells and the presence of tumor recurrence. Our data suggest that colorectal cancer patients with low levels of tumor-infiltrating lymphocytes, a high CD1a/DC-LAMP tumor-infiltrating dendritic cells ratio, and a KRAS mutation in codon 13 are at a high risk of disease recurrence. In ovarian cancer patients we focused on the dynamics of the tumor-infiltrating...
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