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    Wyświetlanie 1-8 z 8
    Tytuł:
    An atlas of the hidradenitis suppurativa transcriptome
    Autorzy:
    Szepietowski, Jacek C.
    Rumienczyk, Izabela
    Kulecka, Maria
    Matusiak, Łukasz
    Jura, Jolanta
    Krajewski, Piotr K.
    Szukała, Weronika
    Mikula, Michał
    Lichawska-Cieślar, Agata
    Opis:
    Introductions Hidradenitis suppurativa (HS) is a chronic inflammatory condition of the skin. Both genetic and environmental factors contribute to the risk of developing HS, but the pathogenesis of this disease is currently not fully understood. The aim of this study was to further current understanding of the molecular background of HS with the use of global transcriptome analyses. Methods Transcriptome profiling of perilesional and lesional skin of five patients with HS and six healthy control patients was performed by next-generation sequencing. Groups of differentially expressed genes characteristic of the skin of patients with HS were shortlisted by bioinformatic analysis. Results RNA sequencing followed by bioinformatic profiling revealed profound enrichment of inflammatory-related processes in both lesional and perilesional skin of patients with HS. There were, however, distinct differences in the gene expression profiles between the lesional and perilesional skin, with 1488 genes differentially expressed. Genes encoding typical proinflammatory cytokines were profoundly enriched within HS lesions. In contrast, those encoding mediators of extracellular matrix organization were highly expressed mostly in the perilesional area. Conclusions Our study provides novel insights into the mechanisms underlying the pathogenesis of HS, and the results also have potential clinical implications in both diagnosis and therapeutics.
    Dostawca treści:
    Repozytorium Uniwersytetu Jagiellońskiego
    Artykuł
    Tytuł:
    Therapeutic Responses to Two New SN-38 Derivatives in Colorectal Cancer Patient-Derived Xenografts and Respective 3D In Vitro Cultures
    Autorzy:
    Ostrowski, Jerzy
    Mikula, Michał
    Dąbrowska, Michalina
    Earnshaw, David
    Kocik-Krol, Justyna
    Unrug-Bielawska, Katarzyna
    Naumczuk, Beata
    Krzykawski, Marcin
    Urbanowicz, Magdalena
    Statkiewicz, Małgorzata
    Rumienczyk, Izabela
    Kaniuga, Ewelina
    Sandowska-Markiewicz, Zuzanna
    Klimkiewicz, Krzysztof
    Cybulska-Lubak, Magdalena
    Kozerski, Lech
    Wydawca:
    International Institute of Anticancer Research
    Cytata wydawnicza:
    ANTICANCER RESEARCH 44: 4219-4224 (2024) ; https://doi.org/10.21873/anticanres.17252
    Opis:
    Polish National Science Center, grant number 2018/31/B/NZ7/02675
    Background/Aim: SN-38, an active metabolite of irinotecan, exhibits toxicity to all proliferating cells, causing dose-limiting and potentially life-threatening side effects. Newly established water-soluble derivatives of SN-38, 7-ethyl-9-(N-morpholinyl)methyl-10-hydroxycamptothecin (BN-MOA) and 7-ethyl-9-(N-methylamino)methyl-10-hydroxycamptothecin (BN-NMe), exhibit a unique mechanism of spontaneous alkylation of aromatic bases in DNA and show greater in vitro activity on cancer cell lines than SN-38. The aim of this study was to compare the therapeutic responses to irinotecan, BN-MOA and BN-NMe in vivo and in vitro in 3D cultures using colorectal cancer (CRC) patient derived xenografts (PDX). Materials and Methods: Seven established PDX tissues were subcutaneously grown on the flanks of NSG or NSG-SGM3 mice and tumor diameters were measured with a caliper. Compounds were administrated intraperitoneally at 40 mg/kg every five days. 3D PDX cultures were performed on 96-well LifeGel plates and cell viability was determined with the CellTiter Glo 3D reagent. Results: Treatment with irinotecan significantly delayed or stopped the growth of 5 out of 7 PDXs, with a greater level of inhibition from BN-MOA compared to irinotecan and BN-NMe. In vitro studies exhibited the same trends in SN-38 and BN-NMe but not in BN-MOA. Conclusion: The new SN-38 derivatives, BN-MOA and BN-NMe, showed enhanced therapeutic effects compared to irinotecan in CRC models. BN-MOA demonstrated superior tumor inhibition in vivo, while BN-NMe had similar in vitro activity to SN-38. These findings highlight the potential of BN-MOA for greater antitumor efficacy in vivo, with BN-NMe showing comparable effectiveness to SN-38 in vitro. Future studies should optimize growth models to better predict anticancer drug responses.
    Dostawca treści:
    Repozytorium Centrum Otwartej Nauki
    Artykuł
      Wyświetlanie 1-8 z 8

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