Similar Datasets
Project description:Carfilzomib (CFZ) is a cornerstone in the treatment of relapsed multiple myeloma (MM). However, its efficacy is limited by resistance mediated by the overexpression of the ABC-transporter P-glycoprotein (P-gp).The signaling pathways driving emergence of P-gp in MM remain unclear. To investigate this, we generated CFZ-resistant AMO-1/CFZ cells with P-gp overexpression by long-term selection. RNA sequencing of control AMO-1 and AMO-1/CFZ, sorted into two subpopulations P-gp HIGH and P-gp LOW, implicated the Ras/MEK/ERK pathway as the most likely signaling cascade involved in P-gp upregulation. We therefore evaluated two clinically used MAPK pathway inhibitors, cobimetinib and ulixertinib, for their ability to re-sensitize AMO-1/CFZ cells to CFZ. Co-administration at non-toxic concentrations enhanced sensitivity 5-fold with cobimetinib and 17-fold with ulixertinib. Analysis of combined MTT assay results, rhodamine efflux experiments, molecular docking, and western blotting revealed distinct actions. Ulixertinib primarily functions as a potent direct P-gp inhibitor. Conversely, non-toxic concentrations of cobimetinib sensitizes cells by suppressing MAPK signaling, though it also exhibits P-gp inhibition at higher concentrations. Both inhibitors at the IC₅₀ concentration reduced P-gp expression. In conclusion, combining CFZ with MAPK pathway inhibitors like cobimetinib or ulixertinib represents a promising strategy to overcome P-gp-mediated resistance in ММ.
2025-11-23 | GSE310880 | GEO
Project description:The purpose is to obtain samples for microRNA analysis in human liver Huh cells using the following viruses obtained by reverse genetics: Zaire Ebola virus wild-type (WT) in the ΔVP30 background (wild), ΔsGP virus (eliminates expression of soluble glycoprotein [GP]) (ssGP), and Δmucin virus (encodes a GP lacking the mucin domain) (mucin).
2016-05-07 | GSE80059 | GEO
Project description:Mounting evidence suggests the high immunogenicity of virus-like particle (VLPs) based vaccines. Although VLP vaccines can be effective, they have not been compared to an envelope glycoprotein (GP)-only vaccine for filoviruses. We conducted a detailed side-by-side comparison of the immunogenicity and protective efficacy of mRNA vaccines encoding for the Marburg virus (MARV) full length GP delivered alone or as a VLP. As expected, co-formulation of the MARV GP and matrix protein VP40 resulted in the formation of VLPs readily detected by electron microscopy after purification from cell supernatants. We vaccinated guinea pigs with a two-component mRNA vaccine encoding for GP and VP40 (from now on referred as VLP vaccine) or a monovalent mRNA vaccine encoding for GP alone. At high vaccine doses, the VLP group demonstrated reduced humoral response as compared to the GP-only group, but both mRNA vaccines fully protected guinea pigs against lethal MARV infection. However, at low doses, GP-only mRNA conferred a 100% protection, whereas the VLP exhibited only a partial protection. In mice the VLP mRNA vaccine was more efficient at inducing GP-specific CD8+ T cells co-expressing IFN-γ and TNF-α, whereas the GP-only mRNA vaccine better induced CD4+ T cells expressing IFN-γ, IL-2 and TNF-α. In addition, in guinea pigs, the VLP vaccine was associated with down-regulation of genes associated with various biological and metabolic processes, including the NF-κB signaling pathway, post-transcriptional silencing of small RNAs, and upregulation of genes involved in the mitochondrial respiratory chain complex. In contrast, the GP-only vaccine upregulated genes involved in interferon signaling. Overall, the VLP mRNA vaccine was less immunogenic and protective, whereas the GP-only mRNA vaccine conferred a robust protection by as little as one µg dose in guinea pigs.
2025-06-27 | GSE298124 | GEO
Project description:Gene expression profile in laser-dissected islets of Langerhans in the inducible RIP-LCMV-GP mouse model for type 1 diabetes (T1D) RIP-LCMV-GP mice express the glycoprotein (GP) of the lymphocytic choriomeningitis virus (LCMV) in the beta-cells (rat insulin promotor, RIP); T1D develops 10-14 after LCMV-infection
2023-10-01 | GSE229287 | GEO
Project description:PURPOSE: The IRSN-23 model uses DNA microarray analysis of tumor tissue to personalize patients into highly sensitive chemotherapy (Gp-R) or less sensitive (Gp-NR) based on the expression of immune-related genes. This study assessed the reproducibility of the IRSN-23 in prospective independent validation sets and investigated its clinical significance and impact on breast cancer subtype classification. METHODS: Tumour tissues were collected from 146 breast cancer patients undergoing preoperative chemotherapy (paclitaxel-FEC) ± trastuzumab in Osaka University Hospital (OUH). Patients were classified into Gp-R or Gp-NR using IRSN-23, and the model was examined for its ability to predict the pathological complete response (pCR). RESULTS: In the OUH prospective dataset, the pCR rate was significantly higher in the Gp-R group (29·3% (11/41)) than in the Gp-NR group (1·4% (1/71)) not using trastuzumab (P = 1·70E-5). CONCLUSION: This study provides prospective validation of the IRSN-23 in predicting chemotherapy efficacy, demonstrating a high degree of reproducibility.
2023-05-19 | GSE230881 | GEO
Project description:In fire ants, a complex colony level phenotype, colony queen number, is completely associated with a single Mendelian factor marked by the gene Gp-9. The first aim of this study was to investigate whether variation in the genomic region marked by Gp-9 is associated with differences in patterns of expression of genes other than Gp-9 in workers. The second aim was to study how the social environment (i.e., presence or absence of nestmate workers with the b allele) can alter individual gene expression patterns. Keywords: Genotype comparison and social form comparison Three-condition experiment: Gp-9 BB monogyne, Gp-9 BB polygyne, and Gp-9 Bb polygyne. Biological replicates: 8 of each sample type from 2004 compared to common reference RNA batch 2004, and 12 of each sample type from 2006 compared to common reference RNA batch 2006. A fourth condition, Gp-9 bb polygyne with 1 biological replicate from 2004 and 1 from 2006, was compared to the respective reference RNA batch. One replicate per array.
2008-06-06 | E-GEOD-11694 | biostudies-arrayexpress
Project description:Among the various modifications of RNA, adenosine-to-inosine RNA editing, catalyzed by adenosine deaminase acting on RNA (ADAR) family, ADAR1 and ADAR2, is the most common nucleotide conversion in mammalian cells. The pathological relevance of ADARs expression has been highlighted in recent human genetic studies. Low expression of the ADAR2 gene is correlated with poor prognosis in breast cancer patients, but the underlying mechanism remains unclear. In this study, we constructed ADAR2-knockdown (ADAR2-KD) murine breast cancer 4T1 cells and found their reduced susceptibility to chemotherapeutic drug doxorubicin. Downregulation of ADAR2 induced the expression of P-glycoprotein (P-gp), resulting in a reduction of intracellular accumulation of doxorubicin. The upregulation of P-gp occurred at the post-transcriptional level due to the decreased miR-195a-3p function. The search for the underlying cause of the induction of P-gp expression in ADAR2-KD 4T1 cells led to the identification of circular RNA (circRNA) circHif1a as a sponge for miR-195a-3p. Indeed, overexpression of circHif1a inhibited miR-195a-3p function, resulting in the upregulation of P-gp expression. Taken together, the decreased expression of ADAR2 in breast cancer plays a critical role in cellular susceptibility to doxorubicin through the regulation of circRNA/miRNA/P-gp pathway. Our findings may contribute to the elucidation of the mechanism of anticancer drug resistance in breast cancer, leading to the overcoming of chemo-resistance.
2026-01-01 | GSE245962 | GEO
Project description:Sinorhizobium medicae 462 Resequencing
| PRJNA499422 | ENA
Project description:To assess the impact of Dnm3os silencing on lung fibrogenesis, anti-Dnm3os gapmers (5mg/kg, 2 distinct designs: GP DNM3OS-1 and GP DNM3OS-3) or control gapmer (5mg/kg, GP Ctrl) formulated for in vivo delivery was instilled intratracheally 4 days and 2 days before intratracheal administration of bleomycin (1 unit/kg) or PBS as well as 4 days after bleomycin or PBS treatment.
2019-04-11 | GSE112827 | GEO
Project description:Analysis of gene trap clones (TCs) revealed the existence of regions where TCs accumulate in the absence of genes. These regions were designated as trap clone accumulation areas (TCAAs). To ascertain the physiological function of TCAAs, negative control regions devoid of genes and TCs (NC1 and NC11), two randomly selected known gene sets (G1 and G11), and a set of genes presumed to be involved in maintaining pluripotency in embryonic stem (ES) cells (GP) were generated and compared with TCAAs. The assay for transposase-accessible chromatin with sequencing (ATAC-Seq) results indicated that TCAAs exhibited characteristics comparable to G1, G11, and GP, suggesting an open chromatin structure. Oct4-chromatin immunoprecipitation-sequencing (ChIP-seq) demonstrated that TCAAs had markedly elevated signals compared to G1 and 11, and a comparable level to that of GP. With regard to H3K4me1 and H3K27ac, which are associated with enhancer activity, TCAAs were observed to exhibit significantly higher levels than G1 and 11 and a comparable level to that of GP. Furthermore, approximately half of the super-enhancers overlapped with TCAAs in an ES cell-specific manner. These findings suggest that TCAAs are involved in maintaining the pluripotency of mouse ES cells.
2025-06-10 | GSE284014 | GEO