Cześć, jestem Julia Lipowicz

Chemotherapy resistance is a major obstacle in the treatment of ovarian cancer, often resulting in disease recurrence and poor prognosis. A key contributor is the overexpression of ABC transporters, including BCRP/ABCG2. This study investigated elacridar (GG918), a dual P-gp and BCRP inhibitor, in TOP-sensitive and TOP-resistant ovarian cancer cells grown in 2D monolayers and 3D spheroid models. ABCG2 expression was quantified via qPCR; BCRP protein levels by western blot and immunofluorescence; drug response by MTT; transporter activity by flow cytometry and microscopic assessment of Hoechst 33342 and MIT retention. Elacridar effectively inhibited BCRP function and significantly enhanced sensitivity to TOP in both 2D and 3D cultures.

Multidrug resistance (MDR) remains a major obstacle in ovarian cancer treatment. We evaluated elacridar, a dual P-gp/BCRP inhibitor, in W1 cells (PAC-sensitive) and PAC-resistant variants in 2D and 3D conditions. MDR1 gene and P-gp expression were determined; P-gp activity by flow cytometry and fluorescence; viability by MTT. Elacridar effectively inhibited transporter activity and increased sensitivity to PAC and DOX, although re-sensitization in 3D was less pronounced. Findings highlight elacridar as a promising compound for reversing MDR.

Cellular information is stored, transferred and modified using different RNA molecules. Microarray chips and NGS, combined with bioinformatics, led to discovery of many ncRNAs. The Human Genome Project and TCGA contributed to formation of data storage and analysis portals widely used in cancer research. We discuss cBioPortal, UALCAN, ENCORI and others, focusing on data integration, simplicity of analysis and visualisation – important for users without bioinformatic or statistical skills.

CRC occurrence inversely correlates with ERβ presence; low ERβ associates with worse OS. Our high-throughput study suggests ERβ represses hypoxic response in CRC cells. We observed altered transcriptional profiles in HCT116 ERβ-overexpressing cells, further stimulated by E2 under hypoxia. Downregulation of VEGFA, PDGFA and ANGPTL4 was validated in DLD-1 cells. Using a DNA-binding mutant we showed direct binding is required. ERβ may also affect HIF1A at transcriptional and translational levels.

Using TCGA transcriptomic data and immunological evidence from ESTIMATE, TIP and TIMER2.0 across solid tumors with tools such as GSEA and GSCA we demonstrate mechanisms and interactions between bromodomain proteins (BrD) of the SP family and immune infiltrates. SP-family genes positively correlate with immune score regardless of tumor type, with T-cell trafficking and infiltration, and with inflammatory response and TNF-α/NF-κB signalling – making them good predictors of high-immune-infiltration phenotypes.

Cancer stemness is essential for tumor development, progression and relapse. We harnessed TCGA and GEO data with Oncomine, PrognoScan, GEPIA2, TIMER2.0, TISIDB, GSEA and R2 to characterise BrD family expression vs. cancer stemness. Upregulation of ATAD2 and SMARCA4, and downregulation of SMARCA2, are consistently associated with stem-cell-like phenotype across 27 tumor types. ATAD2HIGH tumors are enriched with stem-cell markers and c-Myc targets – we propose ATAD2 as a novel druggable target for de-differentiated tumors.