National Repository of Grey Literature 29 records found  previous11 - 20next  jump to record: Search took 0.00 seconds. 
Study of population specific alterations of breast cancer predisposition genes in Czech Republic.
Judasová, Kristýna ; Ševčík, Jan (advisor) ; Holá, Dana (referee)
Breast cancer is the most frequent malignant disease in the female population worldvide. About 10 % of all cases are of hereditary origin. The inactivation of tumor suppressor gene BRCA1 is the main genetic predisposing factor in breast cancer in the Czech Republic. Primarily, BRCA1 participates in DNA double strand break repair. Depending on cell cycle phase, the damage is repaired by homologous recombination or non-homologous end joining. Alternative splicing variants of BRCA1 are frequently detected during the genetic screening of high risk patients. The clinical significance of these variants is unknown. Understanding of the nature of breast cancer genetics is the critical factor for early diagnosis. Based on earlier studies from the Institute of Biochemistry and Experimental Oncology 1st Faculty of Medicine Charles University, two alternative splicing variants which were repeatedly detected in patients, were chosen for functional analysis. The aim of this work is to investigate the impact of alternative splicing variants BRCA1Δ5 and BRCA1Δ10 on DNA double strand breaks repair. Particular variants were over- expressed in the cells of model system. Activity of homologous recombination (HR) and non-homologous end joining (NHEJ) was scored by in vitro DNA repair assay. The cellular localization of...
The functional in vitro analysis of the BRCA1alternative splicing variants
Ševčík, Jan ; Kleibl, Zdeněk (advisor) ; Stopka, Tomáš (referee) ; Macůrek, Libor (referee)
BACKGROUND: The inactivation of the tumor suppressor gene BRCA1 is a predisposing factor for a breast/ovarian cancer development. Formation of cancer-specific alternative splicing variants with aberrant biological properties can represent additional mechanism decreasing the overall BRCA1 activity in DNA double strand break (DDSB) repair. In this study, we analyzed BRCA1 alternative splicing variants BRCA114-15 and 17-19 ascertained previously during the screening of high-risk breast cancer individuals. METHODS: We established a stable MCF-7 cell line-based model system for an in vitro analysis of BRCA1 variants. Using this system, we analyzed the impact of BRCA114-15 and 17-19 variants on DNA repair kinetics using comet assay and confocal immunomicroscopy. The capacity of DNA repair was assessed directly by an in vitro NHEJ assay and indirectly by a mitomycin C sensitivity test. The proliferation activities were determined by a clonogenic assay and growth curves. RESULTS: Overexpression of BRCA114-15 and 17-19 increases the endogenous level of DNA damage, slows down the DDSB repair, and decelerates the initial phase of radiation-induced foci formation and prolongs their persistence. Moreover, BRCA114-15 and 17-19 differentially influence the activity of HR and NHEJ and sensitivity of MCF-7 cells to ionizing...
A DNA double-strand break repair and it's disorders with a relationship to the cancerogenesis
Komžák, Josef ; Ševčík, Jan (advisor) ; Vopálenský, Václav (referee)
The DNA-double strand break (DSB) repair has an essential importance for the genomic integrity maintenance. The main DSB repair pathways are homologous recombination (HR), non-homologous end joining (NHEJ) and single-strand annealing (SSA). The most important protein factors contributing to the maintenance of genomic integrity by direct participation in DSB repair are MRN, ATM, Rad51, BRCA1/2 and PALB2 in the case of HR; Ku70/80 DNA-PKcs, XRCC4 and DNA ligase IV in the case of NHEJ and Msh2-Msh3 and Rad1- Rad10 in the case of SSA. If mutated, these proteins can cause the inability to repair DNA lesions leading to a malignant transformation. The predominant phenotype manifestation of BRCA1/2 inactivation is the hereditary breast and/or ovarian cancer (HBOC). Mutations in ATM have been described as a cause of ataxia telangiectasia and inactivation of NBN gene (Nbs1 protein) causes the Nijmegen breakage syndrome. Other syndromes connected with defects in a DSB repair pathways are Fanconi anemia and Werner syndrome. Detail knowledge of DSB repair process is a mandatory for diagnostics and effective therapy of a number of malignances. An example of practical and clinically relevant utilization of current knowledge about the DSB repair process is the concept of a synthetic lethality as a specific therapy. This...
The role of proto-oncogene crk in invasiveness
Tomášová, Lea ; Rösel, Daniel (advisor) ; Ševčík, Jan (referee)
Proto-oncogene Crk was identified as an oncogenic product of an avian retrovirus in 1988. It is an adaptor protein containing SH2 and SH3 binding domains. Thanks to these domains Crk facilitates protein-protein interactions and therefore plays a crucial role in signal transduction. Crk forms signal complexes with several proteins and hence impacts many cellular processes, among them cell migration, tumorigenezis and invasion of the surrounding tissues. The increased invasiveness allows the tumour cells to detach from the primary tumour and form metastasis which is very problematic feature of cancer. Overexpression of Crk was observed in several tumour tissues, it correlates with an aggressive and metastatic phenotype of the tumours. The subject of this thesis is to describe the mechanisms of how Crk can regulate cellular motility and invasiveness.
The Evaluation of the Financial Situation of a Company
Zouhar, Jan ; Ševčík, Jan (referee) ; Pavláková Dočekalová, Marie (advisor)
The dissertation aims on evaluating the financial situation of the company ITAB Shop Concept CZ, a.s. Depending on data gathered by the financial analysis, it includes suggestions for better optimalization of examined financial ratio and overall improvement of company’s financial situation.
Solution of Receivables in Capital Company
Teturová, Hana ; ing.Jan Ševčík (referee) ; Ing.Jan Ševčík (referee) ; Fedorová, Anna (advisor)
The topic of this thesis work is solution of receivables. At first we make to charted present status care of receivables in capital company. After analysis suggestions follow to innovation as prevention and solution creation non-paid receivables.
Optimizing of electronic bussiness of firm GAME LAND s.r.o.
Smrž, Marek ; Ševčík, Jan (referee) ; Kříž, Jiří (advisor)
This bachelor´s thesis describes and evaluates electronic business of a medium size company which the sphere of business is information technology. Paper is divided into two parts and contains eleven pictures. First section describes the current state of electronic business regarding its content, functionality and graphic user interface. Second section contains improvement concepts for particular fields that will eventually help with general optimization of the e-business. Innovation concepts are strongly customer-oriented and they will improve the usability of web pages and contribute on gain enhancement.
Monolithic milling tools with PVD coatings and their use
Ševčík, Jan ; Sliwková, Petra (referee) ; Jaroš, Aleš (advisor)
The bachelor thesis deals with the monolithic milling tools carbide on the surface which is deposited by a thin layer of rating on. First of all, the thesis describes the method of milling, the basic division of milling operations and milling tools, power analysis tool load. Then, it is analyzed problems of cemented carbides, its production, properties and dividing into groups. After that it is described characteristic of coating methods, especially the PVD method, and its modifications. The last part is devoted to producer’s offers of coated monolithic mills. There are introduced few selected tools and described its characteristics, geometry and application suitability.
Multifunctional building - Houbalova - construction technology project
Ševčík, Jan ; Čech, Václav (referee) ; Henková, Svatava (advisor)
The subject of this thesis is the solution of building technology project poly-functional complex with a focus on execution of construction. Gross building is designed reinforced concrete skeleton combined with masonry. Technology will be developed Code for reinforced concrete monolithic frame and masonry. On the techno-logical stage it will be processed inspection and test plan and the balance of the major sources for the implementation of reinforced concrete structures 1.NP. The thesis is a proposal for construction site, which is complemented by a social facilities and offices. For an overall view of the construction of a multifunctional complex is processed time and financial plan, which will be further elaborated for building construction B. Availability of supply is verified by the design of routes. Like other task will be processed proposal formwork system for con-struction 1.NP Building B.

National Repository of Grey Literature : 29 records found   previous11 - 20next  jump to record:
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