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Possibilities of using advanced MR techniques in pelvic imaging
Ryznarová, Zuzana ; Malíková, Hana (advisor) ; Büchler, Tomáš (referee) ; Lisý, Jiří (referee)
(AJ) The three aims of the work were as follows: 1. Comparison of prostate magnetic resonance (MR) examination results from 1.5 T and 3 T scanners in patients with prostate carcinoma (PCa). MR findings of 103 patients (ages 44-72 years) were compared with histopathological results after radical prostatectomy. The work was focused on the accuracy of predicting local cancer staging and determining prostate tumour location. Patients were divided into three groups (A, B and C) based on the type of MR scanner and protocol used. Patient groups A and B were examined in 1.5T and 3T MR scanners equipped with surface coils in the identical multiparametric MR imaging protocol included dynamic contrast examination (DCE). Patient group C was examined in a 3T MR scanner without DCE. The highest accuracy of predicting the stage of PCa was seen in patients examined in 3 T MR scanner with DCE included in the protocol, however, no significant differences were seen between results from 1.5 T and 3.T MR scanners. No significant difference was also found in the accuracy of determining the location of prostate tumour between 1.5 T and 3T MR examinations, however, there were significant differences between sequences used, with the highest accuracy attained by using a combination of T2 weighted sequences and diffusion...
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Possibilities of using advanced MR techniques in pelvic imaging
Ryznarová, Zuzana ; Malíková, Hana (advisor) ; Büchler, Tomáš (referee) ; Lisý, Jiří (referee)
(AJ) The three aims of the work were as follows: 1. Comparison of prostate magnetic resonance (MR) examination results from 1.5 T and 3 T scanners in patients with prostate carcinoma (PCa). MR findings of 103 patients (ages 44-72 years) were compared with histopathological results after radical prostatectomy. The work was focused on the accuracy of predicting local cancer staging and determining prostate tumour location. Patients were divided into three groups (A, B and C) based on the type of MR scanner and protocol used. Patient groups A and B were examined in 1.5T and 3T MR scanners equipped with surface coils in the identical multiparametric MR imaging protocol included dynamic contrast examination (DCE). Patient group C was examined in a 3T MR scanner without DCE. The highest accuracy of predicting the stage of PCa was seen in patients examined in 3 T MR scanner with DCE included in the protocol, however, no significant differences were seen between results from 1.5 T and 3.T MR scanners. No significant difference was also found in the accuracy of determining the location of prostate tumour between 1.5 T and 3T MR examinations, however, there were significant differences between sequences used, with the highest accuracy attained by using a combination of T2 weighted sequences and diffusion...
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Protein engineering as a tool for the production of antibody derivatives
Šulc, Josef ; Bařinka, Cyril (advisor) ; Mikulecký, Pavel (referee)
This thesis deals with production and properties of disulfide-stabilized single-chain variable fragments of the 5D3 antibody (dsscFv), which specifically recognizes and binds to glutamate carboxypeptidase II (GCPII), an antigen closely related to the prostate carcinoma processes and other tumor diseases. Small antibody fragments are in current focus of development of diagnostic and therapeutic reagents. However, compromised stability of antibody derivatives often results in low production yield or loss of function. Introduction of structural changes by protein engineering is often used to solve the issue. The aim of the study was based on enhancement of protein stability by the introduction of interdomain disulfide bond into the structure of single-chain variable fragment. The effect of modification was evaluated by estimation of production yield and affinity of studied protein. The aforementioned antibody derivative was produced using an Escherichia coli expression system, using specific signal sequences leading the production to the bacterial periplasm. The attempted stabilization was carried out by introducing mutations at LV-G44 and HV-G100 positions, replacing glycines with cysteines. The binding affinity of the derivative for human GCPII was determined using ELISA. This thesis also shows a solved 3D...
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Role of transcription factor Snail in mechanism of development of radiorezistence in prostate carcinoma cell lines
Davidová, Eliška ; Hodný, Zdeněk (advisor) ; Benada, Jan (referee)
The frequent cause of failure of prostate carcinoma radiotherapy and chemotherapy is the emergence of resistance and a progress into the essentially incurable metastatic form of disease. Although the mechanisms of the radioresistance and chemoresistance are still not well understood, recent studies indicate that transcription factor Snail, a key mediator of the epithelial-mesenchymal transition and subsequent metastasis formation, plays a critical role in the development of the chemoresistance and radioresistance in the tumor cells. As the activation of the optimal DNA damage response pathway is the determining factor for the cell survival after chemotherapy and radiotherapy, we hypothesized the role of Snail in the transcription regulation of these processes. In this study, we first analyzed the relationship between Snail and ATM kinase, as the ATM was recently reported to regulate stability of Snail by its phosphorylation. Although, we observed a modest effect of ATM inhibition on Snail levels after cancer cells exposure to ionizing radiation, we did not fully reproduced the recently published findings. Furthermore, we evaluated the role of Snail in transcription regulation of cyclin-dependent kinase inhibitor p21waf1/cip1 . Our data point towards the suppressive role of Snail in p21waf1/cip1...
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Expression of candidate genes for prostate cancer
Krupicová, Daniela ; Mareš, Jaroslav (advisor) ; Holá, Dana (referee)
4 Abstract Prostate cancer is one of the major medical problems within the male population in the Czech Republic and in the world. It is on second place among cancer illnesses with respect to mortality in czech male population. Its incidence strongly increases with age. Prostate cells have a unique ability to accumulate zinc in high concentrations compared to other tissues of human body. It is necessary for the proper physiological function of the prostate. There was detected loss of this accumulation ability in prostate cancer cells, which seems to be a condition to carcinogenesis in prostate cells. In this thesis was investigated the expression of four genes involved in the maintenance of homeostasis of zinc in prostate cells. Genes ZIP1 and ZIP7 encode zinc transporters, genes MT1-F and MT2 encode metallothioneins. There was collected 90 biopsy specimens from patients with prostate cancer or with benign prostatic hyperplasia. mRNA was isolated from these samples, cDNA was obtained by RT-PCR. This cDNA was detected by gel electrophoresis and the results were statistically evaluated. Several correlations was found between gene expression and the clinical data of patients. The most important result, there was found lower levels of expression of genes MT1- F and ZIP1 in samples of patients with cancer...
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Candidate genes screening for prostate cancer
Semaneková, Viera ; Mareš, Jaroslav (advisor) ; Šťovíček, Vratislav (referee)
Prostate carcinoma is considered to be one of the main medical problem in male population. Prostate carcinoma is the most frequently diagnosed malignancy in men and the death rate has the second position within all diagnosed malignancies in Czech Republic (ÚZIS). There is only one reliable diagnostic tool: PSA (prostate specific antigen). Level of PSA is often elevated in men with prostate carcinoma. This diploma thesis is focused on study of changes in gene expression in prostate carcinoma. Three candidate genes were analyzed: VCL (vinculin), SHB (Src homology 2 binding protein) and OCT3 (organic cation transporter 3). According to recent publications, these genes are related to tumor progression and they could have prognostic significance. In this thesis the following methodological approaches were used: 82 prostatic specimens were collected from patients and mRNA was isolated from these specimens; then RT-PCR was used to obtain cDNA, fragments were detected by electrophoresis. At the end statistical methods were used for evaluation. Relative expression of the genes in prostate carcinoma tissue was compared to relative expression of the genes in BPH (benign prostatic neoplasia) tissue. Results showed higher expression of genes SHB and OCT3 in prostate carcinoma tissue in compariscon to BPH...
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Importace of verification treatment irradiaton position of IMRT prostate
KŘÍŽOVÁ, Marcela
Prostate cancer is the most frequent oncological disease in men. Based on the disease phase and extent, patiens with prostate carcinoma diagnosis are treated with number of different therapies including radical prostatectomy, hormone therapy, chemotherapy, brachytherapy, conventional radiotherapy, conformal radiotherapy and combination of these. This Bachelor Thesis deals with prostate carcinoma treatment using a special conformal radiotherapy method - IMRT (Intensity Modulated Radiotherapy). The first section describes the disease charakter from the clinical point of view and the disease diagnosis, followed by treatment modalities. The main part examines and describes IMRT, treatment planning and resultes from statistic evaluation of irradiation position deviations. IMRT technique allows escalation of the irradiation dose while protecting critical structures. In this way the patient can be irradiated with a total dose of 80 grays (Gy). Patients are irradiated in a linear accelerator. Modulation of the radiation beam using multileaf collimator allows irradiation of different segments of target volume with different doses, so that overal homogenity of the irradiation treatment is achieved through nonhomogenous distribution of the dose. Escalation of the irradiation dose is in a close relationship with the irradiaion position and isocentre position kontrol, so that the treatment quality is guaranteed preventing damane to surrounding healthy tissue. Fixing the patient in irradiation position as well as reproductibility of the position is of essentials importance. The isocentre in irradiation position is verified efore every fraction. Verification portal images are acquired using EPID (Electonic Portal Image Device) Portal Vision LC 250 and then compared with reference verification images acquired by CT when planning the treatment. Portal images are made up of two fields of 12x12 cm size under 0 and 90 or 270 degrees. Deviations are recorded in craniocaudal, mediolateral and anterior-posterior axes, and if they exceed 3mm, the irradiation position is corrected on the irradiation table. In this Thesis, deviations in a group of 30 patients were evaluated using the Aria-Offline Review programme which is an accesory to the treatment planning system. In one third of the statistical group of patient, deviations identified using on offline review were compared with deviations identified by start efore each fraction. Dutiny statistical processing, deviations were recorded within ranges 0-3 mm, 3,1-5 mm and over 5mm. 69% of acceptable deviations were recorded within the 0-3 mm range in the craniocaudal axis, 71% in the mediolateral axis and 67% in the anterior-posterior axis. Based on a complete analysis and evaluation of the deviations we can conclude that verification of the irradiation position in treatment of prostate carcinoma using IMRT is essentials to guarantee the irradiation treatment quality. We have also verified that deviations between 0 and 3 mm are acceptable and in no way impair the treatment quality.
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