National Repository of Grey Literature 15 records found  1 - 10next  jump to record: Search took 0.01 seconds. 
Study of pharmacokinetic and pharmacodynamic mechanisms of drug resistance and their modulation in non-small cell lung cancer
Zhang, Yu ; Hofman, Jakub (advisor) ; Pešek, Miloš (referee) ; Trejtnar, František (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Training Workplace Department of Pharmacology and Toxicology Doctoral Degree Program Pharmacology and Toxicology Candidate Yu Zhang Supervisor Assoc. Prof. RNDr. Jakub Hofman, Ph.D. Advisor Title of Doctoral Thesis Study of pharmacokinetic and pharmacodynamic mechanisms of drug resistance and their modulation in non-small cell lung cancer Lung cancer represents one of the most threatening malignancies, which is attributed by its leading morbidity and mortality among all cancer types. Pharmacological interventions have played impressive roles in the clinical management of non-small cell lung cancer (NSCLC) with the outstanding improvements on patients' survival. Nevertheless, the inevitable emergence of drug resistance severely diminishes their efficacies. Traditional chemotherapeutic drugs have been introduced in the treatment of NSCLC decades ago. Countless studies showed that the emergence of multidrug resistance (MDR) is deeply associated with two pharmacokinetic factors: (1) increased drug efflux via ATP-binding cassette (ABC) transporters and (2) enhanced drug deactivation by biotransformation enzymes, e.g., cytochromes P450 (CYPs). Previously, we and others have demonstrated that several novel targeted agents can synergistically...
Clinical use of gene expression of RNA in non-small cell lung carcinoma (NSCLC)
Svatoň, Martin ; Pešek, Miloš (advisor) ; Salajka, František (referee) ; Skřičková, Jana (referee)
The clinical use of determination of gene expression of RNA in non-small cell lung cancer (NSCLC) Abstract Introduction Non-small cell lung cancer (NSCLC) belongs to the most frequent causes of cancer deaths worldwide. Chemotherapy (CHT) has still (except pemetrexed) administered according to stages and patients comorbidities, without the use of other predictive markers. It results into only low objective therapeutical response that differs in indivial patients without more clearly known causes. Aims The aim of our research was to find possible predictive markers in the form of mRNA or miRNA, which would help to reduce the effect of NSCLC / CHT for selected groups of patients. Methods In three groups of patients (42 patients with radically resected adenocarcinomas stage 1; 90 patients with NSCLC who have undergone surgical resection and 59 of them consequently adjuvant CHT; 81 patients palliatively treated in combination platinum derivative + paclitaxel/gemcitabine +/- sequential radiotherapy with advanced squamous NSCLC stages 3B, 4), we examined the effect of expression of mRNA and miRNA until relapse (DFI) / progression (PFS) and overall survival (OS). Expressions were determined with the real-time PCR methodology using UPL probes. Statistical analysis used cox regression model and Kaplan - Meier...
Options for prediction of treatment efficacy of EGFR tyrozine kinase inhibitors in patient with advanced non-small cell lung cancer
Fiala, Ondřej ; Pešek, Miloš (advisor) ; Salajka, František (referee) ; Skřičková, Jana (referee)
Introduction: Targeted therapy with low molecular-weight tyrosine kinase inhibitors (TKI) directed at inhibition of epidermal growth factor receptor (EGFR) is a novel effective option for systemic treatment of locally-advanced or metastatic non-small cell lung cancer (NSCLC). Finding biomarkers that predict the efficacy of targeted treatment may increase the treatment efficacy and also prolong survival of patients. Aims: To assess the frequency of activating EGFR mutations and KRAS mutations in our patients and their role for prediction of EGFR-TKI treatment efficacy. To compare the efficacy and safety of EGFR-TKI and chemotherapy in the first-line treatment of patients harboring activating EGFR mutations. Methods: 613 patients with cytologically or histologically confirmed NSCLC were tested for activating EGFR mutation, of which 448 patients were also tested for KRAS mutation. First-line therapy was evaluated in 54 patients harboring activating EGFR mutations. Mutations were detected using denaturing capillary electrophoresis, and verified by direct DNA sequencing. Survival of patients was assessed using the methodology of Kaplan-Meier, the comparison was calculated using log-rank test. Results: Activating EGFR mutations were detected in 73 (11.9%) patients, more frequently in patients with...
Risk factors for lung cancer-Modulation of the level of antidotes to polycyclic hydrocarbons (PAH) in relation to smoking, tumorous and non-tumorous lung disease and research of a possible strengthening of the immune system against PAH by immunization.
Klimešová, Šárka ; Pauk, Norbert (advisor) ; Marel, Miloslav (referee) ; Pešek, Miloš (referee)
The thesis is divided in two parts; the first of which, following the initial statistics regarding occurrence of the lung cancer and outline of its history, is devoted to the issue of risk factors of development of this disease. Due to the fact that the main focus of the research work is the genotoxic effect of polycyclic aromatic hydrocarbons, a closer attention is paid to them. The beginning of the second part deals briefly with certain lung diseases, i.e. the chronic obstructive pulmonary disease and the lung cancer and the role of inflammation in pathophysiology of both diseases. The rest of the thesis is focused on the research project Modulation of the level of antidotes to polycyclic hydrocarbons (PAH) in relation to smoking, tumorous and non-tumorous lung disease, and research of a possible strengthening of the immune system against the PAH effects by immunization. The main objective of the project was to verify the presence, change of levels and protective effect of the antibodies against the PAH and PAH-DNA adducts in the serum after impact of the pure PAH and cigarette smoke and the application of an epidemiologic study to discover the influence of the level of the anti-PAH antibodies and other tested parameters on the risk of developing a lung disease. In addition to the results proper,...
Assessment of Biological Activity of Colorectal Carcinoma using RT REAL-TIME PCR
Pešta, Martin ; Topolčan, Ondřej (advisor) ; Pešek, Miloš (referee) ; Pecen, Ladislav (referee)
The author in his doctoral thesis, proposed primers and conditions optimized design Quantitative PCR for determining the gene expression of MMP-7, TIMP-1, MMP-2 and TIMP- second Revealed the presence of gene expression of GAPDH TIMP-1 and TIMP-2 in cancer line HT-29 SW480 and SW620. Noted the high level expression of MMP-7 in line HT-29th Expression of the 2-3 orders of magnitude higher than the lines SW480 and SW620. MRNA expression of MMP-2 in line HT-29 noticed. MRNA expression of MMP-2 by the detected lines SW480 and SW620. He found that determining absolute and relative expression in tumor lines is ekvivalentní. significantly higher mRNA expression of MMP-7, TIMP-1, MMP-2 and TIMP-2 in tumor tissue compared to normal tissue. It can be used in therapy. Noticed the presence of correlation of gene expression MMP-7, TIMP-1, MMP-2 and TIMP-2 with survival and DFI. He showed that a higher stage cancer correlated with a higher median momery MMP-2/TIMP-2. 7, Noticed the difference in gene expression between TS, TP and DPD in control and tumor tissue. Scored marginally significant increase in TS expression in colon tumors compared to tumors rectosigmoid and rectum. This finding can be used in treatment decisions. scored marginally significant correlation between the expression of TS and DPD. This finding can be...
New diagnostic methods in bronchology
Votruba, Jiří ; Daneš, Jan (advisor) ; Marel, Miloslav (referee) ; Pešek, Miloš (referee)
The aim of this work has been the development and optimization of methods for early diagnosis of lung cancer, their utility and integration into daily practice. Firstly, we developed a device for measurement of endobronchial temperature (thermobronchoscopy) and found significant difference in endoluminal temperature above tumors and infiltrated lymph nodes compared to healthy regions. We further designed an appliance for near infrared spectroscopy of the bronchial mucosa and identified spectroscopic features useful for localization of solitary pulmonary nodule. The use of the appliance improved yield of endobronchial biopsy compared to endobronchial ultrasound. In the next part of the study, we describe further techniques for early diagnosis of lung cancer including endobronchial ultrasound, optical coherence tomography, confocal fluorescence microendoscopy, reflectance spectroscopy, autofluorescence bronchoscopy, fluorescence bronchoscopy, and narrow band imaging with concise introduction of our experience gained in several pilot projects. Next, we showed the utility of measurement of acetic acid in exhaled air as a promising biomarker for non-invasive identification of patients with symptomatic acid gastroesophageal reflux. Lastly, we demonstrated significant difference in radiation dose in HRCT...
Clinical use of gene expression of RNA in non-small cell lung carcinoma (NSCLC)
Svatoň, Martin ; Pešek, Miloš (advisor) ; Salajka, František (referee) ; Skřičková, Jana (referee)
The clinical use of determination of gene expression of RNA in non-small cell lung cancer (NSCLC) Abstract Introduction Non-small cell lung cancer (NSCLC) belongs to the most frequent causes of cancer deaths worldwide. Chemotherapy (CHT) has still (except pemetrexed) administered according to stages and patients comorbidities, without the use of other predictive markers. It results into only low objective therapeutical response that differs in indivial patients without more clearly known causes. Aims The aim of our research was to find possible predictive markers in the form of mRNA or miRNA, which would help to reduce the effect of NSCLC / CHT for selected groups of patients. Methods In three groups of patients (42 patients with radically resected adenocarcinomas stage 1; 90 patients with NSCLC who have undergone surgical resection and 59 of them consequently adjuvant CHT; 81 patients palliatively treated in combination platinum derivative + paclitaxel/gemcitabine +/- sequential radiotherapy with advanced squamous NSCLC stages 3B, 4), we examined the effect of expression of mRNA and miRNA until relapse (DFI) / progression (PFS) and overall survival (OS). Expressions were determined with the real-time PCR methodology using UPL probes. Statistical analysis used cox regression model and Kaplan - Meier...
New diagnostic methods in bronchology
Votruba, Jiří ; Daneš, Jan (advisor) ; Marel, Miloslav (referee) ; Pešek, Miloš (referee)
The aim of this work has been the development and optimization of methods for early diagnosis of lung cancer, their utility and integration into daily practice. Firstly, we developed a device for measurement of endobronchial temperature (thermobronchoscopy) and found significant difference in endoluminal temperature above tumors and infiltrated lymph nodes compared to healthy regions. We further designed an appliance for near infrared spectroscopy of the bronchial mucosa and identified spectroscopic features useful for localization of solitary pulmonary nodule. The use of the appliance improved yield of endobronchial biopsy compared to endobronchial ultrasound. In the next part of the study, we describe further techniques for early diagnosis of lung cancer including endobronchial ultrasound, optical coherence tomography, confocal fluorescence microendoscopy, reflectance spectroscopy, autofluorescence bronchoscopy, fluorescence bronchoscopy, and narrow band imaging with concise introduction of our experience gained in several pilot projects. Next, we showed the utility of measurement of acetic acid in exhaled air as a promising biomarker for non-invasive identification of patients with symptomatic acid gastroesophageal reflux. Lastly, we demonstrated significant difference in radiation dose in HRCT...
Options for prediction of treatment efficacy of EGFR tyrozine kinase inhibitors in patient with advanced non-small cell lung cancer
Fiala, Ondřej ; Pešek, Miloš (advisor) ; Salajka, František (referee) ; Skřičková, Jana (referee)
Introduction: Targeted therapy with low molecular-weight tyrosine kinase inhibitors (TKI) directed at inhibition of epidermal growth factor receptor (EGFR) is a novel effective option for systemic treatment of locally-advanced or metastatic non-small cell lung cancer (NSCLC). Finding biomarkers that predict the efficacy of targeted treatment may increase the treatment efficacy and also prolong survival of patients. Aims: To assess the frequency of activating EGFR mutations and KRAS mutations in our patients and their role for prediction of EGFR-TKI treatment efficacy. To compare the efficacy and safety of EGFR-TKI and chemotherapy in the first-line treatment of patients harboring activating EGFR mutations. Methods: 613 patients with cytologically or histologically confirmed NSCLC were tested for activating EGFR mutation, of which 448 patients were also tested for KRAS mutation. First-line therapy was evaluated in 54 patients harboring activating EGFR mutations. Mutations were detected using denaturing capillary electrophoresis, and verified by direct DNA sequencing. Survival of patients was assessed using the methodology of Kaplan-Meier, the comparison was calculated using log-rank test. Results: Activating EGFR mutations were detected in 73 (11.9%) patients, more frequently in patients with...
Risk factors for lung cancer-Modulation of the level of antidotes to polycyclic hydrocarbons (PAH) in relation to smoking, tumorous and non-tumorous lung disease and research of a possible strengthening of the immune system against PAH by immunization.
Klimešová, Šárka ; Pauk, Norbert (advisor) ; Marel, Miloslav (referee) ; Pešek, Miloš (referee)
The thesis is divided in two parts; the first of which, following the initial statistics regarding occurrence of the lung cancer and outline of its history, is devoted to the issue of risk factors of development of this disease. Due to the fact that the main focus of the research work is the genotoxic effect of polycyclic aromatic hydrocarbons, a closer attention is paid to them. The beginning of the second part deals briefly with certain lung diseases, i.e. the chronic obstructive pulmonary disease and the lung cancer and the role of inflammation in pathophysiology of both diseases. The rest of the thesis is focused on the research project Modulation of the level of antidotes to polycyclic hydrocarbons (PAH) in relation to smoking, tumorous and non-tumorous lung disease, and research of a possible strengthening of the immune system against the PAH effects by immunization. The main objective of the project was to verify the presence, change of levels and protective effect of the antibodies against the PAH and PAH-DNA adducts in the serum after impact of the pure PAH and cigarette smoke and the application of an epidemiologic study to discover the influence of the level of the anti-PAH antibodies and other tested parameters on the risk of developing a lung disease. In addition to the results proper,...

National Repository of Grey Literature : 15 records found   1 - 10next  jump to record:
See also: similar author names
17 PEŠEK, Martin
2 PEŠEK, Milan
3 PEŠEK, Miroslav
1 Pešek, Marcel
2 Pešek, Marko
17 Pešek, Martin
1 Pešek, Matěj
5 Pešek, Michael
4 Pešek, Michal
2 Pešek, Milan
3 Pešek, Miroslav
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