1 |
Definice expresního vzorce "DASH systému" v transformovaných gliálních buňkách, koexprese proteinu aktivovaných fibroblastů a dipeptidylpeptidázy-IV. / Definition of the expression pattern of DASH system in transformed glial cells, the coupled expression of fibroblast activation protein and dipeptidyl peptidase-IV.Balážiová, Eva January 2012 (has links)
Dipeptidyl peptidase-IV (DPP-IV) is a multifunctional transmembrane glycoprotein removing X-Pro dipeptide from the amino-terminus of the peptide chain. This evolutionary conserved sequence protects a number of biologically active peptides against the unspecific proteolytic cleavage. DPP-IV belongs into the group of "Dipeptidyl peptidase-IV Activity and/or Structure Homologues" (DASH), which, except the canonical DPP-IV, comprises fibroblast activation protein-α/seprase (FAP), and several other molecules. However several of DASH molecules are the enzymes, they execute at least some of their biological functions by non-proteolytic protein-protein interactions. DASH molecules, their substrates and binding partners are parts of "DASH system" which is affected in several pathological process including a cancer. Specifically DPP-IV and its closest structural relative FAP are among others expected to be involved in the development and progression of malignant glioma. In this study we showed the expression and colocalization of DPP-IV and FAP in glioma cells in vitro and in human high grade gliomas. In addition to the DPP-IV/FAP double positive transformed glial cells, we also identified a subpopulation of FAP positive mesenchymal cells located in the perivascular compartment. Moreover we described the...
|
2 |
Příprava konstruktů pro transgenní expresi DPP-IV a FAP / Preparation of contructs for transgenic expression of DPP-IV and FAPKošek, Dalibor January 2011 (has links)
Preparation of contructs for transgenic expression of DPP-IV and FAP Bc. Dalibor Košek Abstract: DASH (Dipeptidyl peptidase-IV Activity and/or Structure Homologues) protein group involves multi-funcional molecules typically bearing enzymatic activity similar to the Dipeptidyl peptidase-IV (DPP-IV, EC 3.4.14.5, identical with lymphocyte differentiation antigen CD26). In general, they cleave multiple regulatory as well as structural peptides and proteins, possessing proline residue on the penultimate position from the N-terminus. We focused on two members of this group: canonical DPP-IV and Fibroblast activation protein alpha (FAP-α). Both are typically type II plasma membrane proteins with specific tissue distribution. Soluble extrecellular forms have also been identified. Available knowledge suggest important roles of these proteins in oncogenesis, executed by their enzymatic activity but also by non-proteolytic interactions. To study their role in gliomagenesis we designed several experimental models exploiting astrocytoma cell lines with defined DPP-IV or FAP-α phenotype. Enzymatically inactive forms and analogues with different subcellular distribution will also be included. These models will allow to assess the impact of DPP-IV and FAP-α on the glial tumor development and the importance of their...
|
3 |
Definice expresního vzorce "DASH systému" v transformovaných gliálních buňkách, koexprese proteinu aktivovaných fibroblastů a dipeptidylpeptidázy-IV. / Definition of the expression pattern of DASH system in transformed glial cells, the coupled expression of fibroblast activation protein and dipeptidyl peptidase-IV.Balážiová, Eva January 2012 (has links)
Dipeptidyl peptidase-IV (DPP-IV) is a multifunctional transmembrane glycoprotein removing X-Pro dipeptide from the amino-terminus of the peptide chain. This evolutionary conserved sequence protects a number of biologically active peptides against the unspecific proteolytic cleavage. DPP-IV belongs into the group of "Dipeptidyl peptidase-IV Activity and/or Structure Homologues" (DASH), which, except the canonical DPP-IV, comprises fibroblast activation protein-α/seprase (FAP), and several other molecules. However several of DASH molecules are the enzymes, they execute at least some of their biological functions by non-proteolytic protein-protein interactions. DASH molecules, their substrates and binding partners are parts of "DASH system" which is affected in several pathological process including a cancer. Specifically DPP-IV and its closest structural relative FAP are among others expected to be involved in the development and progression of malignant glioma. In this study we showed the expression and colocalization of DPP-IV and FAP in glioma cells in vitro and in human high grade gliomas. In addition to the DPP-IV/FAP double positive transformed glial cells, we also identified a subpopulation of FAP positive mesenchymal cells located in the perivascular compartment. Moreover we described the...
|
4 |
Evaluating the role of fibroblast activation protein and fibroblast growth factor 21 in growth hormone-induced adipose tissue fibrosisGeitgey, Delaney Kate January 2020 (has links)
No description available.
|
5 |
Dipeptidyl peptidáza-IV a Fibroblastový aktivační protein v gliomagenezi. / Dipeptidyl peptidase-IV and Fibroblast activation protein in gliomagenesis.Trylčová, Jana January 2018 (has links)
"Dipeptidyl peptidase-IV Activity and/or Structure Homologues"(DASH) represent a newly defined group of multifunctional molecules, typically bearing dipeptidyl peptidase-IV- like hydrolytic activity. Dipeptidyl peptidase-IV (DPP-IV) cleaves out X-Pro dipeptides from the N-terminus of peptides. Other molecules carrying similar enzyme activity, such as Fibroblast activation protein (FAP), DPP-II, DPP8 and DPP9 or even DPP-IV structure-like but hydrolytically inactive molecules (DPP6 and DPP10) also belong to this group. Recent knowledge suggest a substantial role of DASH in cancer pathogenesis. The aim of this study is a preparation of a biological model and its use for understanding the mechanisms of interaction(s) between transformed glial cells and stroma in the processes of origin and development of tumors derived from neuroectoderm. Stable transfected human glioblastoma cell lines with inducible gene expression of DPP-IV, Fibroblast activation protein and their enzymatically inactive mutated forms, were prepared within the project. Prepared cell lines are used as a tool for studying not only the "autocrine" importance of DPP-IV and FAP for the expressing cells in in-vitro, but also for their potential "paracrine" effect(s) within the tumor microenvironment after homotopic implantation into the...
|
6 |
DESIGN, SYNTHESIS, AND PRECLINICAL EVALUATION OF LIGAND-TARGETED CONJUGATES FOR CANCER RADIOTHERANOSTICSSpencer D Lindeman (11205204) 29 July 2021 (has links)
For any drug candidate to be approved by the U.S. Food and Drug Administration, it must meet strict standards for safety and efficacy. While the field of nuclear medicine is over 100 years old, traditional methods such as external beams or systematic administration have rarely met these standards or have limited application. Ligand-targeted therapy and diagnostics, or “theranostics,” has emerged in the past several decades as an exciting field that offers new possibilities to design drugs that are both safe and effective. When applied to nuclear medicine, the field of ligand-targeted radioactive theranostics is younger still, with many critical lessons being discovered and applied currently. This dissertation outlines the necessary principles of radioactive theranostic drug design, then demonstrates the application of several more recent techniques to improve both the efficacy and safety of radioactive theranostics targeting two high priority oncological targets: fibroblast activation protein alpha and folate receptor.
|
Page generated in 0.1139 seconds