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Determination of tumor mRNA in colorectal cancer as screening and forecasting methods
Rupert, Karel ; Holubec, Luboš (advisor) ; Hoch, Jiří (referee) ; Pešková, Marie (referee) ; Dostalík, Jan (referee)
The level of MMP-7, TIMP-1 and MMP-2 mRNA expression was significantly higher in the tumour tissue of colorectal carcinoma than in normal colorectal tissue. It could be possible to inhibit matrix metalloproteinases activity using appropriate antibodies, which could have therapeutic effect on tumour tissue and its vicinity. Some of the preparations are being tested (Bay 12-9566 /Bayer/, BB94 /British Biotechnology/). We have not proved correlation between expression of these genes and disease stage and diagnosis. We have succeeded to prove that if the surgical principles for colon resection performed due to colorectal carcinoma are observed, the resection line does not show any signs of the presence of tumour cells - mRNA for CEA is not present. The level of mRNA for TIMP-1 is present in the resection line at lower levels than in tumour tissue, and this is due to the role that TIMP- 1 plays in the colon. Its level increases not only in all tumour diseases, but also in inflammatory diseases of the colon. The question whether the expression of mRNA for TIMP-1 is also increased outside the resection line and therefore it is a reaction of the colon as an organ will be subject to further research, as will be a potential comparison with samples of colon unaffected by tumour or inflammation. Although the...
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Use of robotic surgery in otorhinolaryngology
Sláma, Karel ; Slouka, David (advisor) ; Betka, Jan (referee) ; Holubec, Luboš (referee)
Dissertation work: Using of robotic surgery in otorhinolaryngology The aim of this dissertation is to introduce the use of robotic surgery in otorhinolaryngology. The theoretical part deals with the description of robotic devices and their use. This part is divided into several chapters: the invention of robots, its development and its usage in medicine. The theoretical part also deals with specifications, safety and main principles of controlling. It also includes the description of the most commonly used robotic system in medicine - the daVinci system. Furthermore, the theoretical part explains, how robots are used in otorhinolaryngology and other surgery fields including the preparation and practical procedures in a robotic operation. The other part describes specific indication criteria for transoral robotic surgery (TORS) including extended uses in otorhinolaryngology, especially in transaxillary thyroidectomy. The special part contains the evaluation of resulting data from a group of otorhinolaryngology patients with T1 and T2 squamous cell carcinoma of base of tongue and supraglottis who were operated on robotically in comparison to traditional open surgery procedures. Key words Robot, use in medicine, da Vinci system, use in otorhinolaryngology
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The prognostic significance of molecular markers of acute myeloid leukemia on the outcome of allogeneie hematopoietic stem cell transplantation
Karas, Michal ; Holubec, Luboš (advisor) ; Faber, Edgar (referee) ; Žák, Pavel (referee)
In this thesis entitled " The prognostic significance of molecular markers of acute myeloid leukemia on the outcome of allogeneic hematopoietic stem cell transplantation " the author deals with the following issues: 1. In the literature overview: the author characterizes the epidemiology, patogenesis, diagnostics, prognosis and treatment of acute myeloid leukemia, focusing on evaluation of different prognostic markers in relation to the treatment of acute myeloid leukemia mainly using allogeneic hematopoietic stem cell transplantation. 1. The methodological section characterizes the following: a) Groups of patients and methods of clinical evaluation in: Detailed characteristics of 60 patients with acute myeloid leukemia with normal karyotype and NPM1 gene mutations in complete remission who underwent allogeneic hematopoietic stem cell transplantation on Haematology and oncology department of University Hospital Pilsen in the years 2005-2014. The evaluation of other parameters of the underlying disease, and a detailed description of transplant procedure (donor selection, the type of pre-transplantation preparation etc.) is also part of characteristics. b) The timing and method of sampling for evaluation of the level of minimal residual disease before transplantation. Description of the method for...
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Prognostic and predictive biomarkers of glial tumors of the central nervous system in the context of personalized medicine
Polívka, Jiří ; Tonar, Zbyněk (advisor) ; Holubec, Luboš (referee) ; Ehler, Edvard (referee)
The glial tumors, so called gliomas, represent the largest group of the primary central nervous system malignancies. Gliomas remain generally an incurable disease progressing from the lower grades of malignancy to the more aggressive tumors in the course of time. This finally leads to the rapid patient's clinical deterioration and eventually the death. Recently there has been a significant expansion of knowledge in the neuro-oncology domain regarding the onset and development of neoplastic disease at the genetic as well as epigenetic level. Novel prognostic and predictive molecular genetic biomarkers are emerging that can be used for more precise diagnosis, for more accurate assessment of a patients' prognosis, or for better selection of therapy and prediction of therapeutic response. The fundamental view of the histological- based classification of central nervous system tumors is gradually changing and the molecular biomarkers are incorporating in addition to histopathology to refine the diagnoses of many tumor entities at the moment. The recent findings from molecular genetics of gliomas together with the results from clinical trials incorporating the various biomarkers are discussed in this thesis. In the first study the biomarker isocitrate dehydrogenases 1 (IDH1) R132H mutation was examined...
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Genetic polymorphism of biotransforming enzymes and risk of pancreatic cancer development in Czech Republic
Vrána, David ; Novotný, Jan (advisor) ; Holubec, Luboš (referee) ; Kološtová, Věra (referee)
Genetic polymorphism of biotransforming enzymes and risk of pancreatic cancer development in Czech Republic Objective: Pancreatic cancer represents one of the biggest challenges of present-day oncology. It effects mainly effects patients in sixth or higher decade of life and due to minimal symptoms in early stages, it is usually diagnosed in locally advanced or metastatic stage of the disease. The only modality which represents a possible chance for long term survival is radical surgical resection. Chemotherapy and possible targeted therapy have only a palliative role. Due to the above mentioned facts, it would be highly useful to identify genetic factors, which could play a role in pancreatic cancer development and create specific screening program which could identify early stages of the disease. We have focused our study on gene polymorphisms in biotransforming enzymes, which modify carcinogen and procarcinogen metabolism and may represent risk factors for pancreatic cancer. Methods: We have included 278 pancreatic cancer patients into this study. As a control group we have chosen healthy volunteers from general practicioner clinics and healthy blood donors. We have focused on gene polymorphisms in biotransforming enzymes CYP1B1, EPHX, NQO1 GSTP1, GSTT1, GSTM1. DNA was amplified by PCR,...
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Use of robotic surgery in otorhinolaryngology
Sláma, Karel ; Slouka, David (advisor) ; Betka, Jan (referee) ; Holubec, Luboš (referee)
Dissertation work: Using of robotic surgery in otorhinolaryngology The aim of this dissertation is to introduce the use of robotic surgery in otorhinolaryngology. The theoretical part deals with the description of robotic devices and their use. This part is divided into several chapters: the invention of robots, its development and its usage in medicine. The theoretical part also deals with specifications, safety and main principles of controlling. It also includes the description of the most commonly used robotic system in medicine - the daVinci system. Furthermore, the theoretical part explains, how robots are used in otorhinolaryngology and other surgery fields including the preparation and practical procedures in a robotic operation. The other part describes specific indication criteria for transoral robotic surgery (TORS) including extended uses in otorhinolaryngology, especially in transaxillary thyroidectomy. The special part contains the evaluation of resulting data from a group of otorhinolaryngology patients with T1 and T2 squamous cell carcinoma of base of tongue and supraglottis who were operated on robotically in comparison to traditional open surgery procedures. Key words Robot, use in medicine, da Vinci system, use in otorhinolaryngology
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Prognostic and predictive biomarkers of glial tumors of the central nervous system in the context of personalized medicine
Polívka, Jiří ; Tonar, Zbyněk (advisor) ; Holubec, Luboš (referee) ; Ehler, Edvard (referee)
The glial tumors, so called gliomas, represent the largest group of the primary central nervous system malignancies. Gliomas remain generally an incurable disease progressing from the lower grades of malignancy to the more aggressive tumors in the course of time. This finally leads to the rapid patient's clinical deterioration and eventually the death. Recently there has been a significant expansion of knowledge in the neuro-oncology domain regarding the onset and development of neoplastic disease at the genetic as well as epigenetic level. Novel prognostic and predictive molecular genetic biomarkers are emerging that can be used for more precise diagnosis, for more accurate assessment of a patients' prognosis, or for better selection of therapy and prediction of therapeutic response. The fundamental view of the histological- based classification of central nervous system tumors is gradually changing and the molecular biomarkers are incorporating in addition to histopathology to refine the diagnoses of many tumor entities at the moment. The recent findings from molecular genetics of gliomas together with the results from clinical trials incorporating the various biomarkers are discussed in this thesis. In the first study the biomarker isocitrate dehydrogenases 1 (IDH1) R132H mutation was examined...
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Genetic polymorphism of biotransforming enzymes and risk of pancreatic cancer development in Czech Republic
Vrána, David ; Novotný, Jan (advisor) ; Holubec, Luboš (referee) ; Kološtová, Věra (referee)
Genetic polymorphism of biotransforming enzymes and risk of pancreatic cancer development in Czech Republic Objective: Pancreatic cancer represents one of the biggest challenges of present-day oncology. It effects mainly effects patients in sixth or higher decade of life and due to minimal symptoms in early stages, it is usually diagnosed in locally advanced or metastatic stage of the disease. The only modality which represents a possible chance for long term survival is radical surgical resection. Chemotherapy and possible targeted therapy have only a palliative role. Due to the above mentioned facts, it would be highly useful to identify genetic factors, which could play a role in pancreatic cancer development and create specific screening program which could identify early stages of the disease. We have focused our study on gene polymorphisms in biotransforming enzymes, which modify carcinogen and procarcinogen metabolism and may represent risk factors for pancreatic cancer. Methods: We have included 278 pancreatic cancer patients into this study. As a control group we have chosen healthy volunteers from general practicioner clinics and healthy blood donors. We have focused on gene polymorphisms in biotransforming enzymes CYP1B1, EPHX, NQO1 GSTP1, GSTT1, GSTM1. DNA was amplified by PCR,...
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The prognostic significance of molecular markers of acute myeloid leukemia on the outcome of allogeneie hematopoietic stem cell transplantation
Karas, Michal ; Holubec, Luboš (advisor) ; Faber, Edgar (referee) ; Žák, Pavel (referee)
In this thesis entitled " The prognostic significance of molecular markers of acute myeloid leukemia on the outcome of allogeneic hematopoietic stem cell transplantation " the author deals with the following issues: 1. In the literature overview: the author characterizes the epidemiology, patogenesis, diagnostics, prognosis and treatment of acute myeloid leukemia, focusing on evaluation of different prognostic markers in relation to the treatment of acute myeloid leukemia mainly using allogeneic hematopoietic stem cell transplantation. 1. The methodological section characterizes the following: a) Groups of patients and methods of clinical evaluation in: Detailed characteristics of 60 patients with acute myeloid leukemia with normal karyotype and NPM1 gene mutations in complete remission who underwent allogeneic hematopoietic stem cell transplantation on Haematology and oncology department of University Hospital Pilsen in the years 2005-2014. The evaluation of other parameters of the underlying disease, and a detailed description of transplant procedure (donor selection, the type of pre-transplantation preparation etc.) is also part of characteristics. b) The timing and method of sampling for evaluation of the level of minimal residual disease before transplantation. Description of the method for...
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Determination of tumor mRNA in colorectal cancer as screening and forecasting methods
Rupert, Karel ; Holubec, Luboš (advisor) ; Hoch, Jiří (referee) ; Pešková, Marie (referee) ; Dostalík, Jan (referee)
The level of MMP-7, TIMP-1 and MMP-2 mRNA expression was significantly higher in the tumour tissue of colorectal carcinoma than in normal colorectal tissue. It could be possible to inhibit matrix metalloproteinases activity using appropriate antibodies, which could have therapeutic effect on tumour tissue and its vicinity. Some of the preparations are being tested (Bay 12-9566 /Bayer/, BB94 /British Biotechnology/). We have not proved correlation between expression of these genes and disease stage and diagnosis. We have succeeded to prove that if the surgical principles for colon resection performed due to colorectal carcinoma are observed, the resection line does not show any signs of the presence of tumour cells - mRNA for CEA is not present. The level of mRNA for TIMP-1 is present in the resection line at lower levels than in tumour tissue, and this is due to the role that TIMP- 1 plays in the colon. Its level increases not only in all tumour diseases, but also in inflammatory diseases of the colon. The question whether the expression of mRNA for TIMP-1 is also increased outside the resection line and therefore it is a reaction of the colon as an organ will be subject to further research, as will be a potential comparison with samples of colon unaffected by tumour or inflammation. Although the...
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