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Utilisation of New Biomarkers for the Optimalization of Diagnostics and Therapy of Tumors of the Gastrointestinal Tract
Šafanda, Martin ; Kučera, Radek (advisor) ; Fínek, Jindřich (referee) ; Svobodová, Šárka (referee)
Utilisation of New Biomarkers for the Optimalization of Diagnostics and Therapy of Tumors of the Gastrointestinal Tract Introduction: Tumor markers are standard diagnostic tools. They are mainly used to monitor the course of the disease and to check the efficacy of the treatment. It is important to observe dynamics. Changing the level of the biomarker can prevent clinical manifestation and lead to early diagnosis of relapse, which in turn means improving the quality of life, including prolonging survival. Recently, we have encountered a number of diagnostic algorithms that suggest algorithms for estimating the risk of tumor presence or the risk of progression of cancer, using statistical methods. Objectives: The aim of this work is to verify new biomarkers for the diagnosis of gastric cancer and to develop an optimal algorithm for their use. Further, to evaluate the importance of cytokeratin markers - Tissue Polypeptide Antigen (TPA) and Tissue Polypeptide Specific Antigen (TPS) for the diagnosis of metastatic colorectal carcinoma in the liver. To carry out a pilot study of FGF23 levels in people with colorectal carcinoma and other gastrointestinal tumors. Methods and patients: Patient samples were analyzed using immunoradiometric, chemiluminescence and fluorescence assays. For each solved problem,...
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Breast cancer in young women: correlation of molecular-genetic, clinical and morphological features
Metelková, Alena ; Fínek, Jindřich (advisor) ; Tesařová, Petra (referee) ; Ryška, Aleš (referee)
In the first part of the dissertation the author summarizes the current knowledge of breast cancer, which is the most frequent malignancy in female population. The author deals with etiology, classification, diagnostics, biological behaviour, therapeutical forms ranging from surgical treatment and radiotherapy, to systemic therapy. In the following part of the manuscript the author describes specifics of breast cancer diagnosed in premenopausal women. She describes how the risk factors, treatment and prognosis differ from the disease in postmenopausal women. Next section of the dissertation includes a retrospective case series evaluating group of patients with breast cancer ≤ 35 years. There were 16 294 cases of breast cancer proven histologically in Biopticka lab Pilsen, ltd. and Sikl's Department of Pathology, Faculty Hospital Pilsen, during 2006-2015. The cohort of patients in our retrospective study includes 356 young women (2,2%) with breast cancer, under 35 years of age by the time of setting the diagnosis. We sorted out a group of 93 patients from the basic cohort, that were or have been treated in the Department of Oncology and Radiotherapy, Faculty Hospital in Pilsen. A control group consists of 100 postmenopausal women ≥ 65 years of age, chosen randomly from all patients treated in the...
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ATM and TGFB1 polymorphism in prediction of late complications of chemoreadiotherapy in patients with locally advanced cervical cancer
Paulíková, Simona ; Petera, Jiří (advisor) ; Kubecová, Martina (referee) ; Fínek, Jindřich (referee)
Cervical cancer is due to high incidence the third most commonly diagnosed gynecological cancer in the Czech republic. More than 50% of these tumors are diagnosed in advanced stage (st. IIB and higher) and therapy is more difficult than in lower stage tumors. The standard treatement method for locally advanced cervical cancers is combined oncological therapy including external beam radiotherapy, brachytherapy and concomitant chemotherapy. This treatement provides good tumor control, but there is also a risk of late complications in irradiated area. Severe late complications affect 10-15% of patients. It is still not possible to predict late complications and therefore detection of valid predictive factors for high tissue radiosensitivity could help to identify patients with increased risk before therapy. Knowledge of such predictive factors would also help to individualize the treatement. New molecular biological methods brought new findings about cancerogenesis, cell cycle regulation and cellular reaction to the radiation damage. It was hypothized, that mutation of genes involved in DNA damage reparation or cell proliferation are one of causes of high tissue radiosensitivity. The aim of our study was to evaluate relations between ATM and TGFß1 polymorphisms and late tissue toxicity in patients treated for...
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Thyroid Dysfunction after Radiotherapy of Head and Neck Cancer
Bernát, Ladislav ; Hrušák, Daniel (advisor) ; Fínek, Jindřich (referee) ; Jenča, Andrej (referee)
Objectictives: Radiation therapy is often applied to patients with head and neck cancer because of a high sensitivity to these cancers. It improves treatment outcomes and permits the preservation of functions and physical form. However, it has been shown that various complications can result from radiation therapy. Hypothyroidism can be one of them as the thyroid gland is frequently included in radiation fields. In spite of that, thyroid hypofunction is not commonly considered a complication of radiotherapy for head and neck cancer. The purpose of this retrospective study was to determine the frequency of thyroid dysfunction in patients after radiotherapy, to compare thyroid hormone levels in irradiated patients with control group and to predict development of thyroid hypofunction in time. Material and method: Thyroid function was measured by means of thyroid stimulating hormone (TSH), free thyroxine (FT4) and free triiodthyronine (FT3) in 43 patiens who had nonthyroid head-neck carcinomas treated by radiotherapy or radiotherapy in combination with other treatment modalities. These data were compared with hormone levels of 40 control group patients treated solely by surgery. Results: In median follow-up period 34 months after radiation, hypothyroidism was found in 35% of irradiated patients. In...
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Prognostic and Predictive Factors in Breast Cancer
Šefrhansová, Lucie ; Fínek, Jindřich (advisor) ; Pešek, Miloš (referee) ; Tesařová, Petra (referee) ; Nekulová, Miroslava (referee)
of dissertation thesis Prognostic and Predictive Factors in Breast Cancer The mRNA Expression of Selected Genes in Normal and Tumor Breast Tissue Samples and Theirs Clinical Value in Breast Cancer L.Šefrhansová Background: The aim of this work was to describe and to evaluate possibilities of prognosis and prediction in breast cancer. Within the framework of this study-work we carry out a prospective clinical study. The aim of this prospective study was to detect mRNA MMP-7, p53 and TIMP-1 expression in normal and tumor breast tissue samples and to determine the clinical and prognostic significance of our results. Prognosis and prediction: The tumor size, lymph node status, presence of distant metastasis, differentiation of the tumor, perivascular invasion, mitotic activity, expression of ER, PR and HER2 receptors are the basic prognostic factors in breast cancer. Age under/above 35 years was included among independent prognostic breast cancer factors in 2005. It is approved to use uPA/PAI to assess prognosis in node negative breast cancer patients. The hormone receptor status and HER-2 receptor status are the only two predictive markers associated with the target therapy. OncotypeDX analysis could be use to predict the disease recurrence interval of patients with estrogen positive and node negative...
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Does the assesment of tumor markers in the context of the last negative conclusions still have any impact in ovarian cancer?
Svoboda, Tomáš ; Fínek, Jindřich (advisor) ; Skalický, Tomáš (referee) ; Hes, Ondřej (referee) ; Vyzula, Rostislav (referee)
Does the assessment of tumor markers in the context of the last negative conclusions still have any impact in ovarian cancer? Svoboda T.: Dept. Of Oncology and Radiotherapy, Univ.Hospital, Plzen, Czech Republic Summary: The incidence of ovarian cancer is very high in Europe and there is still a lot of encertainaity about the best screening method today. The regular use of ultrasound investigation and CA125 testing is not established as a screening, so the greatest number of patients diagnosed with this tumor has a locally advanced disease. Their prognosis is unfavourable even with the treatment by chemotherapy. We describe the role of main factors associated with the primary tumor (staging, grading, histological type) and it's treatment (surgery type and the influence of residual tumor, type and regimen of chemotherapy and inclusion of radiation therapy in the primary treatment) for disease-free and overall survival. We also confirmed that tumor markers (CA125 incl.) used in screening, during treatment measuring response to chemotherapy and for folow-up as an early predictor of disease recurrence have low specificity and sensitivity to be used today. They have role of a prognostic factor - at least some of them - unfortunately with no impact on survival even when palliative chemotherapy can start...
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Analysis of the cytosol of thyroid gland and its contribution in the differential diagnosis of nodular lesions
Pikner, Richard ; Topolčan, Ondřej (advisor) ; Fínek, Jindřich (referee) ; Třeška, Vladislav (referee)
Thyroid nodules represent the most frequent endocrine lession in our population and it is neccessary to differentiate malignant lessions from them. The aim of the study was to validate determination of selected angiogenic, proliferative, and appptotic markers in cytosol tissue extracts. We analysed 166 tissue samples (85 goitres, benign adenomas and 10 malignat tumours in which VEGF, bFGF, Endostatin, Thymidinkinase ans TPS were determined. Main limitation of cytosolic analysis is tissue sample volume, that must be about 1cm3 and interindividual variability caused by tissue sample heterogeneity. Best way is to compare normal with pathological tissue samples from one patient. We fund significant differences amog histological groups in VEGF, bFGF, Endostatin and maily Tymidinkinase and TPS. These differences are not sufficiently huge to distinguish goitres and benign lessions . We also did not find any correlation between cytosolic markers and iminuhistochemistry markers . Cytosol analysis is not able to measure local expression and its differences in anylysed tissue, but it is able to quantitatively determine mean levels of selected markers.
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