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dc.contributor.authorStrachowska, Magdalena
dc.date.accessioned2025-05-26T13:47:17Z
dc.date.available2025-05-26T13:47:17Z
dc.date.issued2024
dc.identifier.urihttp://hdl.handle.net/11089/55645
dc.description1) Grant Narodowego Centrum Nauki w ramach konkursu Preludium 21 - 2022/45/N/NZ5/01371 pt. "Rola kompleksu PARP1/HPF1 w warunkowaniu oporności na doksorubicynę w potrójnie ujemnym raku piersi", kierownik: Mgr Magdalena Strachowska. 2) Grant Narodowego Centrum Badań i Rozwoju w ramach konkursu LIDER/22/0122/L-10/18/NCBR/2019 pt. „Przełamywanie oporności wielolekowej nowotworów na poziomie genomu: opracowanie metody zapobiegającej nadekspresji transporterów ABC w komórkach nowotworowych opartej na inhibitorach enzymów remodelujących chromatynę”, kierownik dr hab. Agnieszka Robaszkiewicz, prof. UŁpl_PL
dc.description.abstractDespite years of research and scientists' efforts to develop novel therapies, cancer is still the second most common cause of death in Poland, and chemotherapy is the most widely used treatment. Nearly half of patients with triple-negative breast cancer experience a relapse after treatment with this type of therapy. This phenomenon is due to the acquisition of multidrug resistance (MDR) as a result of stress factors such as hypoxia, radio- and chemotherapy. Cells with MDR are characterized by decreased sensitivity to cytostatics through, among other things, overexpression of ABC transporters and polynucleation. In a previous work by our team, it was shown that induction of cisplatin resistance in the A549 and MDA-MB-231 cell lines led to the appearance of p300 acetyltransferase on the promoter of the ABCC10 gene. Therefore, in the first part of the study, the effect of the CBP/p300 bromodomain inhibitor I-CBP112 on the downregulation of ABC transporter expression in baseline and clinically relevant, induced resistance lines MDA-MB-231 and A549 was described. In addition, the safety profile of the test compound against normal lines was verified, as well as the ability of I-CBP112 to induce and enhance poly(aneu)ploidy, which is among the mechanisms of cancer cell resistance. Complementary to the present experiments, we prepared two review papers on the phenomenon of polynucleation in cancer, as well as a comparison of pharmacokinetic properties, ADMET parameters and collateral targets of commercially available CBP/p300 inhibitors differing in their mechanism of action. Considering that PARP1 protein is a correlator of CBP/p300 action, in the second part of the thesis I focused my attention on the effect of PARP1/HPF1 complex on the regulation of ABC transporter expression, as well as identification of the transcription factor responsible for PARP1 dependent transcription of ABCC3, ABCC4 and ABCC5 genes.pl_PL
dc.description.sponsorship1) Grant Narodowego Centrum Nauki w ramach konkursu Preludium 21 - 2022/45/N/NZ5/01371 2) Grant Narodowego Centrum Badań i Rozwoju w ramach konkursu LIDER/22/0122/L-10/18/NCBR/2019pl_PL
dc.language.isoplpl_PL
dc.rightsUznanie autorstwa 4.0 Międzynarodowe*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectABC transporterspl_PL
dc.subjectmultidrug resistancepl_PL
dc.subjectPARP1/HPF1 complexpl_PL
dc.subjectepigeneticspl_PL
dc.subjectinhibitors of chromatin remodelling enzymespl_PL
dc.subjectPARP1 inhibitorspl_PL
dc.titlePrzełamywanie oporności wielolekowej nowotworów na poziomie genomu: opracowanie metody zapobiegającej nadekspresji transporterów ABC w komórkach nowotworowych opartej na inhibitorach enzymów remodelujących chromatynępl_PL
dc.title.alternativeOvercoming multidrug resistance in cancer at the genome level: developing a method to counteract overexpression of ABC transporters in cancer cells based on inhibitors of chromatin remodeling enzymespl_PL
dc.typePhD/Doctoral Dissertationpl_PL
dc.page.number129pl_PL
dc.contributor.authorAffiliationUniwersytet Łódzki, Wydział Biologii i Ochrony Środowiska, Katedra Biofizyki Ogólnejpl_PL
dc.contributor.authorEmailmagdalena.strachowska@biol.uni.lodz.plpl_PL
dc.dissertation.directorRobaszkiewicz, Agnieszka
dc.dissertation.reviewerMagalska, Adriana
dc.dissertation.reviewerWolnicka-Głubisz, Agnieszka
dc.dissertation.reviewerSarnowska, Elżbieta
dc.date.defence2025-06-30
dc.disciplinenauki biologicznepl_PL


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Uznanie autorstwa 4.0 Międzynarodowe
Except where otherwise noted, this item's license is described as Uznanie autorstwa 4.0 Międzynarodowe