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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...
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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...
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Breath condensate in the diagnosis of lung diseases
Řihák, Vladimír ; Pauk, Norbert (advisor) ; Salajka, František (referee) ; Musil, Jaromír (referee)
Univerzita Karlova v Praze, 3. lékařská fakulta Disertační práce MUDr. Vladimír Řihák Kondenzát vydechovaného vzduchu v diagnostice plicních nemocí Breath condensate in the diagnostics of lung diseases Školitel: doc. MUDr. Norbert Pauk, Ph.D. SUMMARY Introduction: Examination of exhaled breath condensate is offered as a new, noninvasive diagnostic method in lung diseases. It has been described about 200 markers, which were verified in the condensate, some more, some less developed. The gold standard of examination is exhaled nitric oxide and its metabolites. Other markers are studied in the diagnosis of COPD or pulmonary fibrotic processes. The aim is to use them not only for diagnosis, but also for monitoring dinase, or preventive measures. Methods: 124 patients were examined during 3 years at The University Clinics of Pneumology and Thoracic Surgery in Prague Bulovka and the Pulmonary Department of the Regional Hospital of Tomas Bata in Zlín. Among them were assembled subgroups: a) the health of nonsmokers, b) smokers without any symptoms of respiratory illness with normal lung function tests, c) asthmatics with evidence of uncontrolled disease treatment, d) in asthmatics who had controlled disease, e) patients with exacerbated COPD, f) COPD patients without evidence of exacerbation, g) patients with...
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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...
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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...
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Breath condensate in the diagnosis of lung diseases
Řihák, Vladimír ; Pauk, Norbert (advisor) ; Salajka, František (referee) ; Musil, Jaromír (referee)
Univerzita Karlova v Praze, 3. lékařská fakulta Disertační práce MUDr. Vladimír Řihák Kondenzát vydechovaného vzduchu v diagnostice plicních nemocí Breath condensate in the diagnostics of lung diseases Školitel: doc. MUDr. Norbert Pauk, Ph.D. SUMMARY Introduction: Examination of exhaled breath condensate is offered as a new, noninvasive diagnostic method in lung diseases. It has been described about 200 markers, which were verified in the condensate, some more, some less developed. The gold standard of examination is exhaled nitric oxide and its metabolites. Other markers are studied in the diagnosis of COPD or pulmonary fibrotic processes. The aim is to use them not only for diagnosis, but also for monitoring dinase, or preventive measures. Methods: 124 patients were examined during 3 years at The University Clinics of Pneumology and Thoracic Surgery in Prague Bulovka and the Pulmonary Department of the Regional Hospital of Tomas Bata in Zlín. Among them were assembled subgroups: a) the health of nonsmokers, b) smokers without any symptoms of respiratory illness with normal lung function tests, c) asthmatics with evidence of uncontrolled disease treatment, d) in asthmatics who had controlled disease, e) patients with exacerbated COPD, f) COPD patients without evidence of exacerbation, g) patients with...
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Monitoring of airway inflammation in patients with various types of bronchial obstructionMonitoring of oxidative stress biomarkers in exhaled breath condensate of patients with severe refractory asthma
Sedlák, Vratislav ; Salajka, František (advisor) ; Skřičková, Jana (referee) ; Panzner, Petr (referee)
Monitoring of airway inflammation in patients with various types of bronchial obstruction. Monitoring of oxidative stress biomarkers in exhaled breath condensate of patients with severe refractory asthma. Background: Asthma is chronic inflammatory disease associated with bronchial hyperreactivity. Various cells plays and cellular products are involved in asthma pathogenesis. Oxidative stress plays also a significant role in mechanisms of asthma via action of reactive oxygen (ROS) and nitrogen (NOS) species. These free radicals develop from inflammatory airway reaction and from exogenous exposure of air-pollution (ozone, cigarette smoke). ROS and NOS and its products cause damage of bio- membranes, proteins and nucleic acid. Several studies showed correlation of asthma severity to intensity of oxidative stress. Aim of the study: The main goal of the study was to describe differences in concentrations of various markers of oxidative stress in exhaled breath condensate of severe refractory asthma (SRA) patients and healthy controls (HC). Secondary aim was to show correlation of oxidative stress intensity to severity of eosinophilic inflammation described by peripheral blood eosinophilia or exhaled nitric oxide concentration. Methodology: We harvested exhaled breath condensate in 40 SRA patients and 19...
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Impairment of nasal mucociliary clearance in former smokers with stable chronic obstructive pulmonary disease relates to the presence of a chronic bronchitis phenotype
Koblížek, Vladimír ; Salajka, František (advisor) ; Skřičková, Jana (referee) ; Marel, Miloslav (referee)
AJ Impairment of nasal mucociliary clearance in former smokers with stable chronic obstructive pulmonary disease relates to presence of a chronic bronchitis phenotype Background: Associations between nasal and bronchial impairment have been repeatedly described in chronic obstructive pulmonary disease (COPD) whereas nasal mucociliary clearance (MCC) in COPD patients is not yet fully understood. We studied nasal MCC parameters in COPD patients and compared them with healthy adults (HA) and with cystic fibrosis (CF) patients with compromised MCC. Methodology: Pilot study of seventeen COPD patients without exacerbation; all of them were examined to investigate and compare nasal and bronchial ciliary beat frequency (CBF) and ciliary beat pattern. Main observational study of 98 COPD ex-smokers and subjects from control groups (15 CF and 39 HA) evaluated for nasal MCC time (NMCCt) and by digital video microscopy of nasal mucosa recording ciliary beat frequency (CBF) and ciliary beat pattern (index of ciliary dyskinesia). Results: It was found no difference in mean ciliary beat frequencies between nasal (6.0 Hz ± 1.3) and bronchial (5.9 ± 1.3) mucosa (p = 0.427). We found medium association in degree of ciliary dyskinesia (κ = 0.733). In the main observational study: the NMCCt was decreased in HA (575...
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