|
|
Expression of ABC transporters in cell cultures of non-small cell lung cancer: effect of selected targeted drugs
Žofajová, Barbora ; Hofman, Jakub (advisor) ; Červený, Lukáš (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Barbora Žofajová Supervisor: doc. RNDr. Jakub Hofman, Ph.D. Title of diploma thesis: Expression of ABC transporters in non-small cell lung carcinoma cell cultures: effect of selected targeted drugs ABC transporters form a special family of transmembrane proteins, their function is the active efflux of substrates into the extracellular environment. These transporters are expressed in normal tissues and tumor cells. Thus, they influence drug pharmacokinetics and play a role in the development of multidrug resistance (MDR). Tyrosine kinases have essential functions ranging from proliferation to differentiation and cell death, their mutation can cause carcinogenesis. Finding, exploring, and inhibiting the functions of these targets is a promising strategy to treat cancer. This work aimed to determine whether the selected drugs are involved in pharmacokinetic interactions that are based on inductions of ABC efflux transporter genes and whether they have the potential to affect MDR phenotype of tumor cells. The drugs, which we studied, were three targeted anticancer drugs (capmatinib, pralsetinib, and tazemetostat) and two well- known chemotherapeutic drugs (pemetrexed and methotrexate). First, we...
|
|
|
Modern radiotherapeutic treatment of lung tumors
ŽÁKOVÁ, Klára
In its theoretical part, the bachelor's thesis describes the anatomy of the respiratory system, the types of lung cancers, their symptoms, risk factors and possible treatment. It mainly focuses on lung radiotherapy itself and lung irradiation techniques with regard to the current technical possibilities of radiotherapy. The practical part is represented by the analysis of data from a questionnaire survey examining, in particular, the frequency of the presence of risk factors in patients with lung cancer treated at the RTO of the České Budějovice Hospital. The research part was treatment by questionnaire, the group of patients consisted of a total of 60 respondents. The obtained data were subsequently evaluated with MS Excel tools. In addition to the presence of smoking as the main risk factor, attention was also paid to other risk factors, e.g. occupational stress, general lifestyle or long-term residence in areas with increased radon content in the subsoil. The results confirmed that long-term tobacco smoking remains the most represented risk factor. The processing of answers from the questionnaire also ensures the assumption that a non-negligible risk is also a long-term stay in areas with an increased radon index. The bachelor's thesis can serve as a comprehensive study material for future radiology assistants as an overview of modern lung cancer radiation treatment. But it can also be used in professional articles in magazines, or be a source of information for those interested in this topic.
|
|
|
The clinical relevance of biomarkers for aggression assessment and prognosis in non-small cell lung cancer
Pražáková, Markéta ; Topolčan, Ondřej (advisor) ; Ludvíková, Marie (referee) ; Molino, Rafael (referee)
Aim: The aim of this thesis was to measure a large spectrum of biomarkers in serum or plasma of patients with operable stage of NSCLC and to evaluate and compare the clinical utility of these biomarkers in the three most important clinical applications for NSCLC: diagnosis, prognosis and postsurgery follow up care. Patients and methods: Total of 22 biomarkers with the most promising profiles were monitored: 8 standard tumor markers (cytokeratines Cyfra 21-1, TPA, TPS, and MonoTotal, CEA, SCC, TK, Chromogranin A) and 14 potential useful biomarkers including pro-inflammatory cytokines IL-6, IL-8, MCP-1, pro-angiogenic cytokine VEGF, matrix metaloproteinases MMP-1, MMP-2, MMP-7, MMP-9 and their inhibitors TIMP-1 and TIMP-2, adhesion molecules ICAM-1, VCAM-1, growth factor IGF-1, and PAI-1 stimulating tumor growth and angiogenesis. With a view of evaluating the clinical relevance of these markers for NSCLC we measured serum or plasma levels of these 22 markers in group of 93 patients with NSCLC undergoing radical surgery and in group of 20 patients with benign lung disease. For biomarker measurement were used conventional immunoanalytic routine methods (IRMA, REA, CLIA, MEIA, TRACE, ELISA) and multiplex immunoanalytic method. Results: Cyfra 21-1, MonoTotal, TPA, TPS, CEA, SCC, Chromogranin A, TIMP-1, MMP-1,...
|
|
|
Relationship of protein SIVA and signaling pathways Hedgehog/GLI and mTOR to the origin and progression of non-small cell lung cancer.
Vachtenheim, Jiří ; Lischke, Robert (advisor) ; Zemanová, Milada (referee) ; Vodička, Josef (referee)
Non-small cell lung cancer belongs to most frequent malignant tumours at all worldwide. Despite significant progress in knowledge about etiopathogenesis and targeted anticancer therapy, basic scientific research in this particular field and development of more effective treatment remains challenging. In case of its inadequate activation, the Hedgehog signaling pathway is involved in non-small cell cancer development. P53 is well known tumour suppressor gene, that serves as anticancer barrier. Its activity is mostly determined by the transcriptional activation of many pro-apoptotic genes, one of which is SIVA-1. Recently, it has been surprisingly shown, that SIVA-1 has also pro-oncogenic properties in a mouse model of non-small cell lung cancer. The aim of this study was to clarify the importance of Hedgehog signaling pathway and protein SIVA-1 and their potential relationship in development and progression of human non-small cell lung cancer. In selected cell lines of human non-small cell lung cancer, expression of each single component of Hedgehog signalign pathway was detected. In the tissue samples of tumour obtained from 39 patients that underwent surgery for non-small cell lung cancer and selected cell lines of the same tumour, expression of SIVA-1 protein was revealed. These findings indicate...
|
|
|
Radiotherapy of lung cancer in the Karlovy Vary Region
NEJEDLÁ, Klára
The study is aimed to radiotherapy of lung cancer in patients permanently living in the Karlovy Vary region. The number of newly diagnosed pulmonary cancer in the Czech Republic is nearly six and half thousand case a year. This number testifies a slight reduction in the long-term incidence of the disease. The most risky factor in the development of lung cancer is definitely smoking. The objective of the work was avaluated a set of patients from the "KKN" hospital in Cheb who are treated for lung cancer over the period from 2009 to 2013 and to highlight the importance of the representation of regional oncological centers in the treatment of lung cancer. Data about 382 patients who were treatment initiaton between 2009-2013 in the Cheb's regional cancer center, were assembled from the hospital information systém (NIS) in hospital in Cheb. Data collection was of age, where do they live, WHO staging, way of treatment, work information and year of death. Another objective of the work was to verify on the supposition that there is a higher incidence of lung cancinoma in the Karlovy Vary region where there is elevated radon index of the geological subsoil. It was found out that the ratio of patients with this disease is virtually identical in Cheb region and Karlovy Vary region. Over the period from 2009 to 2013 there were treated 617 patients for lung cancer in the Chebs's regional cancer center of whitch 382 were treated with radiotherapy. In my opinion that the closure of the radiotherapy department in the past would seriosly complicate the treatment of oncological patients from all over the region, especially a large number of patients who need of palliative treatment.
|
|
|
The clinical relevance of biomarkers for aggression assessment and prognosis in non-small cell lung cancer
Pražáková, Markéta ; Topolčan, Ondřej (advisor) ; Ludvíková, Marie (referee) ; Molino, Rafael (referee)
Aim: The aim of this thesis was to measure a large spectrum of biomarkers in serum or plasma of patients with operable stage of NSCLC and to evaluate and compare the clinical utility of these biomarkers in the three most important clinical applications for NSCLC: diagnosis, prognosis and postsurgery follow up care. Patients and methods: Total of 22 biomarkers with the most promising profiles were monitored: 8 standard tumor markers (cytokeratines Cyfra 21-1, TPA, TPS, and MonoTotal, CEA, SCC, TK, Chromogranin A) and 14 potential useful biomarkers including pro-inflammatory cytokines IL-6, IL-8, MCP-1, pro-angiogenic cytokine VEGF, matrix metaloproteinases MMP-1, MMP-2, MMP-7, MMP-9 and their inhibitors TIMP-1 and TIMP-2, adhesion molecules ICAM-1, VCAM-1, growth factor IGF-1, and PAI-1 stimulating tumor growth and angiogenesis. With a view of evaluating the clinical relevance of these markers for NSCLC we measured serum or plasma levels of these 22 markers in group of 93 patients with NSCLC undergoing radical surgery and in group of 20 patients with benign lung disease. For biomarker measurement were used conventional immunoanalytic routine methods (IRMA, REA, CLIA, MEIA, TRACE, ELISA) and multiplex immunoanalytic method. Results: Cyfra 21-1, MonoTotal, TPA, TPS, CEA, SCC, Chromogranin A, TIMP-1, MMP-1,...
|
guest ::
