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Dendritic cells in solid tumors of urogenital system
Minárik, Ivo ; Jarolím, Ladislav (advisor) ; Stříž, Ilja (referee) ; Soukup, Viktor (referee)
In the last 15 years we can observe many clinical studies which focus on recovery of immune reaction against tumor cells and possibly tumor elimination. At first it is necessary to understand the interaction of immune system with tumor cells so that effective vaccines are developed. In the first part of this work, I focus on the preparation of dendritic cell vaccine for patients with ovarian and prostate cancer. We show that dendritic cells can be differentiated from peripheral mononuclear cells in both tumors in vitro, we were able to pulse dendritic cells with apoptotic tumor cell, in case of ovarian cancer with autologous tumor cells, in case of prostate cancer with prostate cancer cell lines LNCaP and DU145. Pulsed mature dendritic cells expressed maturation marker CD83, costimulatory molecules CD80 a CD86 and produced significant cytokines. These dendritic cells also induced specific T lymphocyte response. In the next part of the work we focused on practical aspects of preparation of dendritic cell vaccine in the patient with prostate cancer and optimization of preparation in GMP conditions. The best medium for cultivation turned out to be Cell Gro. Maturation of dendritic cell with poly I:C led to the highest proliferation of specific T lymphocytes and at the same time to the lowest proliferation of...
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není uveden
Soukup, Viktor ; Babjuk, Marek (advisor) ; Mareš, Jaroslav (referee) ; Novák, Jaroslav (referee)
Immunohistochemical examination of microvascular density can be an additional prognostic factor in patients with superficial urinary bladder carcinoma, nevertheless, more extensive studies need to be carried out. Maximal microvascular density correlated with a recurrence free interval and in a case of bigger group of patients could be statistically significant. The statistical correlation between MVD and a nuclear p53 accumulation is that significant that we assume the p53 importance in the angiogenesis regulation of superficial urinary bladder carcinoma. The p53 positivity in non-tumor mucosa of urinary bladder in patients with superficial bladder cancer correlates with higher risk of tumor recurrence. According to our results the reason of urinary bladder carcinoma multifocality is genetic instability present in the whole urothelium at the time of tumor diagnosis. The PAX5 gene expression is a frequent finding in superficial transitional cell carcinoma of the bladder. From the prognostic point of view, high levels of PAX5 expression seem to be connected with higher recurrence and progression rates. The extent of lamina propria invasion seems to be a clinically relevant prognostic factor for progression of T1 bladder transitional cell carcinoma. Finding T1b tumor is connected with the risk of understaging....
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Molecular biology of renal tumours in clinical use
Trávníček, Ivan ; Hora, Milan (advisor) ; Soukup, Viktor (referee) ; Veselý, Štěpán (referee)
Molecular biology of renal tumours in clinical use MUDr. Ivan Trávníček Summary Aim: To identify tissue biomarker that are predictive of the therapeutic effect of sunitinib in treatment of metastatic clear cell renal cell carcinoma (mCRCC). Material and methods: Our study included 39 patients with mCRCC; these were selected from 119 patients who received sunitinib in our hospital between the years 2005 - 2012 according to inclusion criteria of the study. Patients were stratified into two groups based on their response to sunitinib treatment; non-responders (progression), and responders (stable disease, regression). The effect of treatment was measured by comparing imaging studies performed before the initiation of treatment, with those done between 3rd and 7th months of treatment. Histological samples of tumour tissue and healthy renal parenchyma, acquired during surgery of the primary tumour, were examined with immunohistochemistry to detect tissue biomarkers (mTOR, p53, VEGF, HIF1, HIF2, CAIX). The average levels of biomarker expression in both, tumour tissue, as well as in healthy renal parenchyma were compared between the two groups of patients. Results were evaluated using Student's T-test. Results: When considering the results of the group of responders, statistically significant differences in marker...
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Detection of circulating tumour cells and their clinical application in patients with bioptically proven prostate cancer.
Čapoun, Otakar ; Soukup, Viktor (advisor) ; Zachoval, Roman (referee) ; Veselý, Štěpán (referee)
1 ABSTRACT Introduction and aim of the study Circulating tumor cells (CTCs) are a promising tool of identifying patients with castration- resistant prostate cancer (CRPC) who will benefit from often demanding cytotoxic therapy. The aim of this work was to evaluate the prognostic significance of CTC in docetaxel-treated CRPC patients. During the project, we also tested the various methods of CTC cultivation and studied their genetic profile as well as the genetic profile of histological specimen at the time of diagnosis. Patients and methods A total of 39 patients who met the CRPC criteria and were indicated for docetaxel chemotherapy were included in the prospective study. Blood collection for CTC analysis was done in all patients before chemotherapy and on the first day of the fourth or fifth cycle of docetaxel. In parallel, CTCs were cultivated. Isolation and detection of CTC was done using the AdnaTest system, which consists of immunomagnetic separation and subsequent detection of mRNA from the CTC lysate. The primary objective of the study was to evaluate the overall survival (OS) of patients. Survival analysis was performed using the Kaplan-Meier method of estimating the survival distribution function. The impact of individual factors was tested using the Log-rank test, the Wilcoxon test and the Cox...
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Molecular biology of renal tumours in clinical use
Trávníček, Ivan ; Hora, Milan (advisor) ; Soukup, Viktor (referee) ; Veselý, Štěpán (referee)
Molecular biology of renal tumours in clinical use MUDr. Ivan Trávníček Summary Aim: To identify tissue biomarker that are predictive of the therapeutic effect of sunitinib in treatment of metastatic clear cell renal cell carcinoma (mCRCC). Material and methods: Our study included 39 patients with mCRCC; these were selected from 119 patients who received sunitinib in our hospital between the years 2005 - 2012 according to inclusion criteria of the study. Patients were stratified into two groups based on their response to sunitinib treatment; non-responders (progression), and responders (stable disease, regression). The effect of treatment was measured by comparing imaging studies performed before the initiation of treatment, with those done between 3rd and 7th months of treatment. Histological samples of tumour tissue and healthy renal parenchyma, acquired during surgery of the primary tumour, were examined with immunohistochemistry to detect tissue biomarkers (mTOR, p53, VEGF, HIF1, HIF2, CAIX). The average levels of biomarker expression in both, tumour tissue, as well as in healthy renal parenchyma were compared between the two groups of patients. Results were evaluated using Student's T-test. Results: When considering the results of the group of responders, statistically significant differences in marker...
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Molecular mechanism of renal cell carcinogenesis
Chocholatý, Matúš ; Babjuk, Marek (advisor) ; Soukup, Viktor (referee) ; Eret, Viktor (referee)
The receptor for advanced glycation end products (RAGE), soluble RAGE (sRAGE) and its ligands are involved in the pathogenesis of cancer. Glyoxalase I (GLO1) is an enzyme which detoxifies advanced glycation end product (AGE) precursors. Four polymorphisms of RAGE (rs1800625 RAGE -429T/C, rs1800624 -374T/A, rs3134940 2184A/G, rs2070600 557G/A (G82S), and GLO1 rs4746 419A/C(E111A)) were determined by PCR-RFLP in 214 patients with ccRCC. A group of 154 healthy subjects was used as control. We found significant differences in the allelic and genotype frequencies of GLO1 E111A (419A/C) SNP between patients and controls-higher frequency of the C allele in ccRCC-58.6 vs. 44.5 % in controls, OR (95 % CI) 1.77 (1.32-2.38), p=0.0002 (corrected p=0.001); OR (95 % CI) CC vs. AA 2.76 (1.5-4.80), p=0.0004 (corrected p= 0.002); and AC+CC vs. AA 2.03 (1.23-3.30), p=0.0034 (corrected p=0.017). The values of sRAGE in a subgroup of 132 patients were evaluated before and three weeks, three and six months after surgery and in cancer relapse. According to relapse of the cancer, the patients were divided into two groups. The postoperative elevation of sRAGE was seen in group of ccRCC without relapse. Stable postoperative sRAGE were in group with relapse. We have not detected the difference between sRAGE in ccRCC group...
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Activity of the cathepsin B in patient with the bladder cancer
Dušek, Pavel ; Babjuk, Marek (advisor) ; Soukup, Viktor (referee) ; Broďák, Miloš (referee)
Bladder cancer is the most common malignant neoplasm of the urogenital tract. Of non- invasive diagnostic methods in clinical practice normally only is used cytology to its limits. While there are several commercially available tests that have the character of a tumor marker. None of them, however, has not yet been recommended for the standard diagnosis or monitoring of patients with bladder cancer. Cathepsin B is a thiol - dependent protease found in normal circumstances in the lysosomes of mammalian cells. Cathepsin B are lysosomes involved in the degradation of proteins and has various functions in maintaining cell metabolism in normal conditions. The incidence of cathepsin B or its proteins and their high activity is described in a number of neoplastic diseases. About its importance for urological tumors has so far been only very few reports. Activity of the cathepsin B in patients with invasive bladder cancer were examined by determining its expression in tumor tissue and determining the concentrations of cathepsin B and pro-cathepsin B in their serum urine. Our results confirm that the diagnostic efficiency of the pro-cathepsin B urine urine is high. All so far published studies are focused on the investigation of biologically active proteins. Pro- cathepsin B is the biologically inactive...
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Dendritic cells in solid tumors of urogenital system
Minárik, Ivo ; Jarolím, Ladislav (advisor) ; Stříž, Ilja (referee) ; Soukup, Viktor (referee)
In the last 15 years we can observe many clinical studies which focus on recovery of immune reaction against tumor cells and possibly tumor elimination. At first it is necessary to understand the interaction of immune system with tumor cells so that effective vaccines are developed. In the first part of this work, I focus on the preparation of dendritic cell vaccine for patients with ovarian and prostate cancer. We show that dendritic cells can be differentiated from peripheral mononuclear cells in both tumors in vitro, we were able to pulse dendritic cells with apoptotic tumor cell, in case of ovarian cancer with autologous tumor cells, in case of prostate cancer with prostate cancer cell lines LNCaP and DU145. Pulsed mature dendritic cells expressed maturation marker CD83, costimulatory molecules CD80 a CD86 and produced significant cytokines. These dendritic cells also induced specific T lymphocyte response. In the next part of the work we focused on practical aspects of preparation of dendritic cell vaccine in the patient with prostate cancer and optimization of preparation in GMP conditions. The best medium for cultivation turned out to be Cell Gro. Maturation of dendritic cell with poly I:C led to the highest proliferation of specific T lymphocytes and at the same time to the lowest proliferation of...
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Topical issues of the regulation of international air carriage
Soukup, Viktor ; Pauknerová, Monika (advisor) ; Kučera, Zdeněk (referee)
Executive Summary The thesis "Current Issues of Regulation of International Air Transport" is dedicated to the very up-to date issues of international air transport of persons and goods, especially focused not only on actual regulation in Warsaw and Montreal Convention but also on commercial, technical and operational issues. The thesis is specifically structured it consists of four basic parts (chapters), dedicated to above mentioned aspects. A the beginning it briefly mentiones conception and sources of of regulation of air transport, second chapter focuses on Warsaw and Montreal Conventions with a view to transportation documents. Third chapter presents commercial issues, especially the airspace concept and freedoms of air. The last chapter deals with selected technical and operational issues. Supplement to the thesis "Current Issues of Regulation of International Air Transport" from 2007 reflects a period of 5 years since its submition. Since than a European Regulation 261/2004 has played an important role regarding carrier's liability. Minor changes of Warsaw-Montreal system are described next. Part dealing with commercial issues contains "Open Skies" treaty which liberalized transatlantic market. At the end the author contemplates on future trends and related necessity of regulation.
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