|
|
Polymeric delivery systems for immunooncotherapy
Šírová, Kateřina ; Etrych, Tomáš (advisor) ; Konvalinka, Jan (referee)
Oncological diseases are among the most common causes of death in developed countries and for some of them, current medicine still does not have satisfactory results. Designing of polymer therapeutics characterized by high molecular weight and controlled drug delivery is one of the perspective ways of development of new therapeutic protocols. Nowadays, scientists also focus on the research on anticancer immunological mechanisms and their potential use in cancer therapy. Constitutive activation of signal transducer and activator of transcription 3 (STAT3) has been described in many types of malignancies. The function of STAT3 is very complex, the aberrant activation in cells of tumor microenvironment is related to many predominantly prooncogenic processes. This bachelor thesis is focused on synthesis of peptide inhibitor of STAT3 signaling, phosphopeptide pYLPQTV, and its conjugates with polymer carrier based on N-(2-hydroxypropyl)methacrylamide (HPMA). The inhibitor and the polymeric conjugates have been characterized by several physico-chemical techniques; also, effect on proliferation of cancer cells have been tested in in vitro conditions, which proved slightly cytotoxic activity. A more detailed study and an optimization of methods for in vitro characterization will be necessary to further...
|
|
|
Use of polymer prodrugs containing cucurbitacin D for the treatment of experimental tumors
Hrabánková, Klára ; Šírová, Milada (advisor) ; Grobárová, Valéria (referee)
Chemotherapy is still the most widely used anti-cancer treatment. The majority of chemotherapeutics inhibit proliferating cells generally, not selectively cancer cells. The side effects associated with chemotherapy can be partly limited by conjugating a cytotoxic drug with a polymer nanocarrier. Such binding facilitates solubility in aqueous solutions, reduces systemic toxicity; and passively targets the drug directly into the tumour through the enhanced permeability and retention (EPR) effect. This thesis focuses on testing polymer conjugates based on N-(2-hydroxypropyl)methacrylamide (HPMA) carrying cucurbitacin D (CuD), a naturally occurring compound with potential anti-cancer activity. The mechanism of action is not elucidated yet, but several studies have depicted the inhibitory effect on signal transducer and activator of transcription 3 (STAT3) transcription factor. A STAT3 signalling pathway is overexpressed in several cancer cell lines and is also involved in the differentiation of myeloid- derived suppressor cells (MDSCs). We examined the therapeutic effect of the HPMA copolymers based on CuD in combined therapy with other polymer chemotherapeutics. CuD conjugates have shown in vitro cytotoxic effect on several model cancer cell lines. The combination with conjugates carrying doxorubicin...
|
|
|
Polymeric delivery systems for immunooncotherapy
Šírová, Kateřina ; Etrych, Tomáš (advisor) ; Konvalinka, Jan (referee)
Oncological diseases are among the most common causes of death in developed countries and for some of them, current medicine still does not have satisfactory results. Designing of polymer therapeutics characterized by high molecular weight and controlled drug delivery is one of the perspective ways of development of new therapeutic protocols. Nowadays, scientists also focus on the research on anticancer immunological mechanisms and their potential use in cancer therapy. Constitutive activation of signal transducer and activator of transcription 3 (STAT3) has been described in many types of malignancies. The function of STAT3 is very complex, the aberrant activation in cells of tumor microenvironment is related to many predominantly prooncogenic processes. This bachelor thesis is focused on synthesis of peptide inhibitor of STAT3 signaling, phosphopeptide pYLPQTV, and its conjugates with polymer carrier based on N-(2-hydroxypropyl)methacrylamide (HPMA). The inhibitor and the polymeric conjugates have been characterized by several physico-chemical techniques; also, effect on proliferation of cancer cells have been tested in in vitro conditions, which proved slightly cytotoxic activity. A more detailed study and an optimization of methods for in vitro characterization will be necessary to further...
|
guest ::
