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The study of signaling pathways that modulate multidrug resistance
Dvořák, Pavel ; Souček, Pavel (advisor) ; Daum, Ondřej (referee) ; Benson, Veronika (referee)
The study of signaling pathways that modulate multidrug resistance The theme of cancer cell resistance to anti-cancer drugs including the common mechanisms of resistance development and the theory of cancer stem cells was introduced in the Introduction to the doctoral thesis. The theoretical part was focused more deeply on the two topics - the role of ATP-binding cassette (ABC) transport proteins and chromosomal abnormalities in the development of cancer chemoresistance. The possible therapeutic potential for the treatment of cancer was stressed for both topics. The Results were composed of the commentaries on the five published works, which the author of the thesis conducted as the main author. The first work brought the evidence supporting the hypothesis of the existence of ABC gene expression profiles (signatures), which are common to multiple types of tumors and are associated with significant clinical consequences. These general ABC gene expression profiles could possibly form a new hallmark of cancer. The second work studied more closely a group of acute myeloid leukemia patients, who did not achieve complete cytogenetic remission after two attempts to maintain remission of the malignant disease. The new entity, consisting of patients with the translocation t(2;11)(p21;q23) without the...
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Molecular biological detection of viral and bacterial pathogens and their relationship
Kašpírková, Jana ; Hes, Ondřej (advisor) ; Daum, Ondřej (referee) ; Boudová, Ludmila (referee) ; Putzová, Martina (referee)
1 We report a case of an eccrine syringofibroadenoma (ESFA) associated with well- differentiated squamous cell carcinoma. The patient was an 85-year-old man, who had a 2.5x2.5-cm, brown-colored ulcerated nodule, with a fragile, flesh-colored bleeding surface located beyond the metacarpophalangeal joint of the second finger of his left hand. Histopathologically, there were areas of a well-differentiated squamous cell carcinoma, alternating with the typical area of ESFA characterized by anastomosing cords, strands, and columns of epithelial cells extending from the crusted epidermis into a thickened, edematous, myxoid vascular-rich dermis. Immunohistochemically, the areas with dysplastic epithelium were positive for p16, whereas the benign ESFA parts tested negative. Human papillomavirus was detected in the lesional tissue by polymerase chain reaction, and the subsequent sequencing analysis demonstrated that the virus was close to human papillomavirus type 107. 2 The authors report a case of basaloid carcinoma involving the anus and rectum of a 57-year- old woman. Microscopically, the tumor showed unusual morphologic features strongly resembling a spiradenocylindroma because it consisted, in most parts, of basaloid cell nodules arranged in a jigsaw-puzzle fashion containing or surrounded by eosinophilic basal...
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Diagnostic morphological features of PDGFRA-mutated gastrointestinal
Daum, Ondřej ; Hes, Ondřej (advisor) ; Mandys, Václav (referee) ; Ehrmann, Jiří (referee) ; Zámečník, Josef (referee)
Daum O., Grossmann P., Vanecek T., Sima R., Mukensnabl P., Michal M. (2006): Diagnostic morphological features of PDGFRA-mutated gastrointestinal stromal tumors: Molecular genetic and histological analysis of 60 cases of gastric GISTs. Ann. Diagn. Pathol. In Press Summary In this study, 60 gastrointestinal stromal tumors (GISTs) of the stomach were analyzed to elucidate the possible relation of their morphology to mutation status of KIT and PDGFRA genes. The patients included 27 men and 33 women with a mean age of 63,8 years (range 12 to 92). Only one tumor occurred before the age of 21 years. KIT mutations were detected in 31 cases (51,7%), PDGFRA mutations in 22 cases (36,7%), and seven cases (11,7%) were KIT and PDGFRA wild type. When the mutation status was correlated with histological features of the tumors, epithelioid or mixed epithelioid/spindle cell pattern and mast cell infiltration were found as the most reliable signs of PDGFRA mutation. Neoplastic rhabdoid cells and multinucleated giant cells, also previously reported as features of PDGFRA mutated GISTs, seemed to be less specific but still helpful markers in our study. Finally, tumor infiltrating lymphocytes and myxoid stroma do not seem to be valuable histological signs. Daum O., Klecka J., Ferda J., Treska V., Vanecek T., Sima R., Mukensnabl...
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