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Polymer drug carries based on HPMA copolymers facilitating solid tumour drug targeting and pH-triggered activation
Chytil, Petr ; Ulbrich, Karel (advisor) ; Sedláček, Jan (referee) ; Stiborová, Marie (referee) ; Smetana, Karel (referee)
2. Summary of the PhD. Thesis Introduction The use of synthetic polymer carriers of anticancer drugs represents a promising approach to cancer therapy. Conjugation of cýotoxic drugs with polymers may reduce their toxicity and immunogenicity, eliminate undesirable body interactions, improve their solubility, bioavailability and stability (enzymatic. thermal, etc.), and prolong blood clearance' Moreover, polStmer drug carriers may enable specific delivery to the diseased tissue and controlled drug release in therapeutically active form. Since the first papers were published in the late 1970's the concept of polymer drug carrier systems has been generally accepted. In principle basic water-soluble poll,tner drug delivery systems consist of three parts: of polymer carrier, biodegradable spacer and drug. Preferably, drugs are covalently bound to the pol}mers via spacers, which enable controlled release of active drug in the target tissue or cells. Probably, most of the studied polymer carriers of cancerostatic drugs have been designed as lysosomotropic systems, where the drug could be released by enzymes rn lysosomes of tumour cells. In recent years pH-triggered hydrolytic drug release has been intensively studied. Here, the presence of enzynes is not essential, as the drug might be released in endosomes in...
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Glycobiology of squamous epithelium - in vitro and in vivo
Dvořánková, Barbora ; Smetana, Karel (advisor) ; Mandys, Václav (referee) ; Ulbrich, Karel (referee)
The skin is the largest organ of human body and its severe damage can cause even death of a patient. As the allografting of skin can not create permanent closure of wounds, the treatment (especially in cases of burn injuries) is rather demanding and prolonged. In my work I focused on determination of glycobiologic characteristcs of squamous cell epithelium, especially the skin, under normal and pathological conditions. Those results which we have obtained could be used for development of new methods of keratinocyte cultivation for clinical purposes. Epidermis was the very first human tissue that was prepared in vitro and returned back to the patient however the results of these transplantations were not satisfactory. (...) A new method of cultivation and transfer of keratinocytes on polymer support was developed. This way of cultivation of epidermal grafts exhibits some advantages compared with confluent sheets attached to textile. Namely the shortening of the cultivation period and the deletion of enzymatic detachment of the cells, that negatively influence their viability, are the main benefits. First of all the hydrogel support protects the cells from infection and desiccation after its application to the wound bed. So the optimal microclimate for the attachment and spreading of transplanted cells is...
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Expanzi aktivovaných CD8+ t-lymfocytů lze výrazně zvýšit podáváním komplexů IL-2 a anit-IL-2protilátky
Tomala, Jakub ; Kovář, Marek ; Strohalm, Jiří ; Etrych, Tomáš ; Ulbrich, Karel ; Říhová, Blanka
By using the model of adoptively transferred transgenic CD8+ cells (OT-I) labeled by CFSE dye, we have measured clonal expansion, proliferation and expression of surface markers after various stimulation.We have studies prophylactic effect of complexes, alone or in combination with other cytokines, on various cancer cell lines in vivo. Our results indicate such approach is very promising and could be potent therapeutical tool in tratment of cancer
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Polymerní konjugát doxorubicinu na bázi HPMA, působící ve shodě s protinádorovou imunitou nositele
Šírová, Milada ; Rossmann, Pavel ; Mrkvan, Tomáš ; Strohalm, Jiří ; Šubr, Vladimír ; Plocová, Daniela ; Ulbrich, Karel ; Říhová, Blanka
Polymeric conjugate Dox-HPMA-HuIg directly targets the tumour due to the EPR effect, it is not detrimental towards the immune system of the host, and acts in concert with the anti-tumour immune responses
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Glykosylace povrchové membrány EL-4 buněk: vliv volného nebo N-(2-hydroxypropyl)methacrylamide (HPMA) vázaného doxorubicinu
Kovář, Lubomír ; Etrych, Tomáš ; Šubr, Vladimír ; Strohalm, Jiří ; Sklenář, Jan ; Chytil, Petr ; Ulbrich, Karel ; Říhová, Blanka
In those experimenst we studied the possible impace of CD43 as highly glycosylated molecule in cells exposed to free doxorubicin (Dox) or to conjugates consisting of HPMA copolymer backbone to which the drug is conjugated via enzymatically (PK1 conjugate) or pH sensitive, hydrolytically cleavable bond (hydrazone conjugate, HYD).
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Imunostimulační a imunoprotektivní vlastnosti makromolekulárních protinádorových léčiv
Říhová, Blanka ; Strohalm, Jiří ; Šírová, Milada ; Etrych, Tomáš ; Mrkvan, Tomáš ; Šubr, Vladimír ; Plocová, Daniela ; Kovář, Marek ; Ulbrich, Karel
Polymeric conjugates of doxorubicin, non-targeted or antibody targeted cure mice from experimental EL4 T cell lymphoma and induce specific, systemic long-lasting anti/tumor resistance
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