Immunoprotective character of polymer cytotoxic drugs

Abstract

Dizertační práce RNDr. Milada Šírová Školitelka: prof. RNDr. Blanka Říhová, DrSc. Sektor imunologie a gnotobiologie Mikrobiologický ústav Akademie věd České republiky Praha, květen 2010 CHARLES UNIVERSITY IN PRAGUE Faculty of Natural Sciences PhD. Thesis in Immunology Cytostatic and Immunomodulatory Properties of Polymeric Prodrugs RNDr. Tomáš Mrkvan Supervisor: Prof. RNDr. Blanka �íhová, DrSc. Department of Immunology and Gnotobiology Institute of Microbiology Academy of Sciences of the Czech Republic Prague, March 2006 UNIVERZITA KARLOVA V PRAZE PŘÍRODOVĚDECKÁ FAKULTA IMUNOPROTEKTIVNÍ VLASTNOSTI POLYMERNÍCH CYTOSTATIK IMMUNOPROTECTIVE CHARACTER OF POLYMER CYTOTOXIC DRUGS 2 DOKTORSKÉ STUDIJNÍ PROGRAMY V BIOMEDICÍNĚ UNIVERZITA KARLOVA V PRAZE A AKADEMIE VĚD ČESKÉ REPUBLIKY PROGRAM: IMUNOLOGIE PŘEDSEDA OBOROVÉ RADY: DOC. RNDR. VLADIMÍR HOLÁŇ, DRSC. ŠKOLICÍ PRACOVIŠTĚ: MIKROBIOLOGICKÝ ÚSTAV AVČR, V. V. I. AUTOR: MILADA ŠÍROVÁ ŠKOLITEL: PROF. RNDR. BLANKA ŘÍHOVÁ, DRSC. ŠKOLITEL KONSULTANT (BYL-LI): NE S DISERTACÍ JE MOŽNO SE SEZNÁMIT NA DĚKANÁTĚ PŘÍRODOVĚDECKÉ FAKULTY UNIVERZITY KARLOVY V PRAZE 1 OBSAH I. ÚVOD .................................................................................................... 3 I.1. Cílená léčba nádorových onemocnění................................................... 3 I.2....

18 I. INTRODUCTION Cancer is a serious health problem worldwide. In economically developed countries, it is a second most frequent cause of death after cardiovascular dis- eases, and the number of oncological patients continuously increases with the increasing age of population. The mainstay of cancer therapy is combination of surgery, radiation and chemotherapy. Whilst surgery and radiation are relatively precise and suitable to achieve a local control over the tumor, chemotherapy exerts a systemic ef- fect. These three modalities, when properly combined and sequenced, can cure a substantial number of hematological cancers and a smaller, but still significant subset of various solid tumors. Most cytostatic/cytotoxic drugs that are now in common use target the cells with high proliferation rate. The non-selective character of chemotherapy leads to increased toxicities towards normal rapidly proliferating cells. This means that the drugs have to be used at suboptimal doses, leading to development of (multi)drug resistance, metastatic disease and, eventually, to failure of the therapy. Innovative therapeutic strategies need to be developed in order to achieve better treatment outcome. For that purpose, several approaches are be- ing applied. First, sophisticated genomic and proteomic research could identify...