Překonání rezistence nádorů k chemoterapii pomocí konjugátů na bázi HPMA kopolymerů
Multidrug resistance (MDR) is a common cause of failure in chemotherapy for malignant diseases. Cancer cells develop MDR most often via the up-regulation of P- glycoprotein (P-gp) expression. P-gp is an efflux pump with broad specificity belonging to ATP-binding cassette (ABC) transporters which dec...
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ndltd-nusl.cz-oai-invenio.nusl.cz-4060832020-07-15T07:09:31Z Překonání rezistence nádorů k chemoterapii pomocí konjugátů na bázi HPMA kopolymerů Overcoming cancer resistance to chemotherapy through HPMA copolymer conjugates Sivák, Ladislav Kovář, Marek Smetana, Karel Palich Fučíková, Jitka Multidrug resistance (MDR) is a common cause of failure in chemotherapy for malignant diseases. Cancer cells develop MDR most often via the up-regulation of P- glycoprotein (P-gp) expression. P-gp is an efflux pump with broad specificity belonging to ATP-binding cassette (ABC) transporters which decreases the intracellular concentration of various drugs. We designed polymeric conjugates based on an N-(2-hydroxypropyl)methacrylamide (HPMA) bearing a cytostatic drug and/or P-gp inhibitor and tested their cytostatic/cytotoxic activity in vitro and their therapeutic efficacy in vivo in MDR tumors. We demonstrated that HPMA copolymer conjugates bearing both the cytostatic drug (doxorubicin (Dox) or pirarubicin) and the P-gp inhibitor (derivative of reversin 121 (R121) or ritonavir) possess remarkable cytostatic and cytotoxic activity in MDR tumor cell lines in vitro and superior antitumor activity in vivo. Notably, the HPMA copolymer conjugate bearing both Dox and R121 showed significant antitumor activity in both P388/MDR and CT26 mouse tumor models and was capable to completely cure 6 out of 8 mice with established CT26 tumors. We explored the potential of micelle-forming HPMA copolymer-poly(propylene oxide) (PPO) diblock bearing Dox to overcome MDR in vitro and in vivo. The HPMA copolymer-PPO diblock... 2019 info:eu-repo/semantics/doctoralThesis http://www.nusl.cz/ntk/nusl-406083 eng info:eu-repo/semantics/restrictedAccess |
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English |
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Doctoral Thesis |
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NDLTD |
description |
Multidrug resistance (MDR) is a common cause of failure in chemotherapy for malignant diseases. Cancer cells develop MDR most often via the up-regulation of P- glycoprotein (P-gp) expression. P-gp is an efflux pump with broad specificity belonging to ATP-binding cassette (ABC) transporters which decreases the intracellular concentration of various drugs. We designed polymeric conjugates based on an N-(2-hydroxypropyl)methacrylamide (HPMA) bearing a cytostatic drug and/or P-gp inhibitor and tested their cytostatic/cytotoxic activity in vitro and their therapeutic efficacy in vivo in MDR tumors. We demonstrated that HPMA copolymer conjugates bearing both the cytostatic drug (doxorubicin (Dox) or pirarubicin) and the P-gp inhibitor (derivative of reversin 121 (R121) or ritonavir) possess remarkable cytostatic and cytotoxic activity in MDR tumor cell lines in vitro and superior antitumor activity in vivo. Notably, the HPMA copolymer conjugate bearing both Dox and R121 showed significant antitumor activity in both P388/MDR and CT26 mouse tumor models and was capable to completely cure 6 out of 8 mice with established CT26 tumors. We explored the potential of micelle-forming HPMA copolymer-poly(propylene oxide) (PPO) diblock bearing Dox to overcome MDR in vitro and in vivo. The HPMA copolymer-PPO diblock... |
author2 |
Kovář, Marek |
author_facet |
Kovář, Marek Sivák, Ladislav |
author |
Sivák, Ladislav |
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Sivák, Ladislav Překonání rezistence nádorů k chemoterapii pomocí konjugátů na bázi HPMA kopolymerů |
author_sort |
Sivák, Ladislav |
title |
Překonání rezistence nádorů k chemoterapii pomocí konjugátů na bázi HPMA kopolymerů |
title_short |
Překonání rezistence nádorů k chemoterapii pomocí konjugátů na bázi HPMA kopolymerů |
title_full |
Překonání rezistence nádorů k chemoterapii pomocí konjugátů na bázi HPMA kopolymerů |
title_fullStr |
Překonání rezistence nádorů k chemoterapii pomocí konjugátů na bázi HPMA kopolymerů |
title_full_unstemmed |
Překonání rezistence nádorů k chemoterapii pomocí konjugátů na bázi HPMA kopolymerů |
title_sort |
překonání rezistence nádorů k chemoterapii pomocí konjugátů na bázi hpma kopolymerů |
publishDate |
2019 |
url |
http://www.nusl.cz/ntk/nusl-406083 |
work_keys_str_mv |
AT sivakladislav prekonanirezistencenadorukchemoterapiipomocikonjugatunabazihpmakopolymeru AT sivakladislav overcomingcancerresistancetochemotherapythroughhpmacopolymerconjugates |
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1719326428533620736 |