Relation of tumor genotype and phenotype to diagnosis, prognosis and prediction of colorectal cancer

Colorectal cancer is one of the most common type of malignity. Despite of the existence of numerous studies focused on this carcinoma, there are still many unknown features regarding its diagnosis, treatment or prognosis. In the thesis we focused on the identification of novel prognostics markers that could be useful for the stratification of patients based on the disease outcomes. In the first study we immunohistochemically assessed expression of two proteins associated with cancer stem cells in the samples of primary colorectal cancer and matched liver metastasis. Goal of the study was to evaluate relation among expression of CD44 and CD133 and overall survival and disease free interval in our set of patients. We observed that increased ratio of CD133 positive compared to CD133 negative tumor glands resulted in longer disease free interval, finding which is opposite to the general view on the CD133 role in the cancer development. Our hypothesis is that we analyzed confined group of patients and followed a bit different goal, where we measured ratio between positive and negative glands in the view-field and not the intensity of staining as the previous studies did. Our second study was focused on the transcriptional analysis of the selected set of twelve genes using frozen samples from colorectal..

Comparative genomic prediction of novel transmembrane adaptor proteins and their expression analysis.

Transmembrane adaptor proteins play an important role in signal transduction cascades emanating from immune cell receptors leading to cellular effector mechanisms. Despite the lack of enzymatic function, their sequence contains interaction motifs which organize other proteins in time and space and initiates building of the signaling complexes. Functionally the most important and for the longest time known TRAPs are the ones associated with immune receptors. Their deficiency has severe impacts on the signal transduction and knock-out mice show dramatic phenotypes. The deficiency of Lat - the first discovered TRAP, which is not constitutively associated with immune receptors - has comparable effects on signaling in lymphocytes. The difference between the first group of TRAPs and Lat is not only the type of association with receptors, but also the lack of tyrosine - based activation motifs (ITAMs) in Lat, but Lat contains several other binding motifs also based on the phosphorylation of tyrosine. The group of TRAPs similar to Lat up today contains eight members, but all of them, except of Lat, has only very mild or undetectable phenotype in the knock-out mice. In this work I searched the protein databases for proteins with the characteristics of TRAP using the bioinformatic tools. Based on our..

Functional annotation of short protein linear motifs - bioinformatic analysis

Dep. of Physiology and Develop. Biology (obsolete)Katedra fyziol. živočichů a vývoj. biol. (zrušena)Přírodovědecká fakultaFaculty of Scienc

Sonic Hedgehog and Triiodothyronine Pathway Interact in Mouse Embryonic Neural Stem Cells

Neural stem cells are fundamental to development of the central nervous system (CNS)—as well as its plasticity and regeneration—and represent a potential tool for neuro transplantation therapy and research. This study is focused on examination of the proliferation dynamic and fate of embryonic neural stem cells (eNSCs) under differentiating conditions. In this work, we analyzed eNSCs differentiating alone and in the presence of sonic hedgehog (SHH) or triiodothyronine (T3) which play an important role in the development of the CNS. We found that inhibition of the SHH pathway and activation of the T3 pathway increased cellular health and survival of differentiating eNSCs. In addition, T3 was able to increase the expression of the gene for the receptor smoothened (Smo), which is part of the SHH signaling cascade, while SHH increased the expression of the T3 receptor beta gene (Thrb). This might be the reason why the combination of SHH and T3 increased the expression of the thyroxine 5-deiodinase type III gene (Dio3), which inhibits T3 activity, which in turn affects cellular health and proliferation activity of eNSCs