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Genetic factors in lymphoproliferative malignancies Focus on CHEK2 gene in lymphomas with comparison to distinct solid tumors
Havránek, Ondřej ; Trněný, Marek (advisor) ; Papajik, Tomáš (referee) ; Veselý, Pavel (referee)
Genetic factors in lymphoproliferative malignancies. Focus on CHEK2 gene in lymphomas with comparison to distinct solid tumors. MUDr. Ondřej Havránek Summary of PhD thesis: Background: The checkpoint kinase 2 gene (CHEK2) codes for an important mediator of DNA damage response pathway that among others interacts with the p53 protein. Mutations in the CHEK2 gene increase the risk of several cancer types, however, their role in non- Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) is not clear. The most frequent TP53 gene R72P polymorphism was analyzed in several studies in NHL but not in HL. Methods: We have performed mutation analysis of the whole CHEK2 gene coding sequence in 340 NHL patients and the segment coding for CHEK2 forkhead-associated (FHA) domain in 298 HL patients and compared the results with our analyses of CHEK2 in breast, colorectal and pancreatic cancers. The TP53 R75P genotype was assessed in the same lymphoma populations. Both genes were analyzed using denaturing high-performance liquid chromatography. Results: The overall frequency of CHEK2 alterations within FHA-coding region was significantly higher in NHL and HL patients (19/340 - 5.6%; 17/298 - 5.7%, respectively) compared to non-cancer controls (19/683 - 2.8%; p = 0.03 and 0.04, respectively). These alterations were associated with...
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Biological diversity of breast carcinoma cells in relation to the sensitivity on the antitumor treatment
Netíková, Irena ; Veselý, Pavel (advisor) ; Květina, Jaroslav (referee) ; Abrahámová, Jitka (referee)
Biological diversity of cancer cells isolated from breast carcinoma samples has been studied by in vitro exposure to cytotoxic agents. Primary cells from individual primary breast tumours and malignant effusions were in the first phase of the study used for experimental assessment of chemosensitivity/resistance using the standard MTT assay. Cytotoxic effects after short-term cultivation with antineoplastic drugs were evaluated. In several approachable cases relation to the clinical course of the disease was followed; in 4 out of 7 cases good correlation was found. The effect of combination of two cytotoxic drugs on cell viability was studied on EM-G3 cells, showing interesting results with some drug combinations (e.g. combination of paclitaxel and cisplatin resulted in a lower effect than cisplatin alone). Possibility of cell chemosensitisation by tamoxifen pretreatment was tested. Very low chemosensitisation effects of tamoxifen were observed. As a model cell population for diversification development study a new clonal cell line, EM-G3, was established. The EM-G3 line was derived from a primary lesion of human infiltrating ductal breast carcinoma. The EM-G3 represents a unique, spontaneously immortalized clonal cell line, evidently derived from premalignant progenitors of breast carcinoma. The cells are...
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název v anglickém jazyce není uveden
Krásná, Luboslava ; Veselý, Pavel (advisor) ; Křepela, Evžen (referee) ; Červinka, Miroslav (referee)
An in vitro cultivation technique has been developed that allows to reproducibly obtain and propagate a heterogenous population of epithelial cells from samples of normal mammary glands, breast tumours and subcutaneous metastases of breast cancer. The epithelial origin of cultured cells was proved by their cytokeratin profile, and EMA and ESA protein expression. The technique uses a feeder layer of irradiated NIH 3T3 cells to support clonal growth of even single isolated cells. Cultures were successfully established from 96% of surgical tumour biopsy specimens (69 out of 72, volume of sample about 1 cm3) and 67% of true-cut biopsy specimens (28 out of 42, volume 0.01 cm3). Two and more in vitro passages were obtained with 74% (53 out of 72) of surgical specimens and 31% (13 out of 42) of truecut biopsy specimens. This is the first report of successful in vitro propagation of cells obtained from breast cancer via true-cut biopsy. In cell populations analyzed for the growth properties, the culture lifetime, related to the number of colony-forming cells, varied for cells from benign tumours between 22 and 40 cell populations and for malignant tumours between 21 and 51. The population doubling time varied betwen 18 and 62 hours for benign cultures and 10 and 127 hours for malignant cultures, with average 32...
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Cartesian Genetic Programming in Evolutionary Art
Veselý, Pavel ; Hyrš, Martin (referee) ; Petrlík, Jiří (advisor)
This thesis deals with use of Cartesian Genetic Programming (CGP) in Evolutionary Art (EvoArt). Text presents introduction to the topic. The rest of the thesis focuses on the process of design, implementation and testing of new method of application CGP in EvoArt. The proposed method uses CGP to create 2D vector images. Web application for EvoArt creation is made to demonstrate this method. Achieved results are presented and evaluated.
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Processes leading to achievement of higher surface quality of steel castings
Tomková, Jana ; Veselý, Pavel (referee) ; Záděra, Antonín (advisor)
The subject of this thesis is to verify effect of aluminium powder in ground refractory coatin, which is intended for casting od steel castings to organic bonded moulds. The pre-sence of aluminium powder in ground coating was expertised on term of coating in itself - that means immunity to heat shock, penetration etc., and in term of influence on formation of surface defects etc. Outputs of this thesis are: setting of optimum amount of aluminium powder in ground coating and statistically verified analysis of effects of modified coating in term of creation of defects
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Optimation of heavy steel castings
Pernica, Vítězslav ; Veselý, Pavel (referee) ; Šenberger, Jaroslav (advisor)
Diploma thesis deal with definnig the casuses of stell castings defects in the DSB EURO s.r.o Foundry. The main target is to optimise technological parameters for avoiding the surface casting defects. The first stage is the identification of the defects, describing of the main reasons and mechanic. Defect quantification is make from measuring of area and volume of the mended defects. In association with surface defects, the number of the crackings was observed. Finally there are suggested correction actions based on the previous investigation.
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