Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA272138 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Global mRNA expression profiles of murine primary PDAC cells following JQ1 or SAHA monotherapy as well as JQ1-SAHA combination therapy were collected using Affymetix mouse whole genome array (Mouse Genome 430A 2.0 Array) . Primary PDAC cells isolated from Ptf1aCre/+;Kras+/LSL-G12D;p53lox/lox (Kras;p53) mice were treated either with JQ1 (100 nM) or SAHA (2000 nM) or vehicle 10% (2-Hydroxypropyl)-β-cyclodextrin (Sigma-Aldrich) or as combination therapy with the indicated dosage for monotherapy. Total RNA isolation was performed after 6 hours of treatment. Primary PDAC cells from Ptf1aCre/+;Kras+/LSL-G12D;p53lox/lox (Kras;p53) mice treated either with JQ1, SAHA, vehicle or JQ1-SAHA combination were analyzed by global gene expression analysis.
2015-09-20 | E-GEOD-64836 | biostudies-arrayexpress
Project description:Global mRNA expression profiles of murine primary PDAC cells following JQ1 or SAHA monotherapy as well as JQ1-SAHA combination therapy were collected using Affymetix mouse whole genome array (Mouse Genome 430A 2.0 Array) . Primary PDAC cells isolated from Ptf1aCre/+;Kras+/LSL-G12D;p53lox/lox (Kras;p53) mice were treated either with JQ1 (100 nM) or SAHA (2000 nM) or vehicle 10% (2-Hydroxypropyl)-β-cyclodextrin (Sigma-Aldrich) or as combination therapy with the indicated dosage for monotherapy. Total RNA isolation was performed after 6 hours of treatment.
2015-09-20 | GSE64836 | GEO
Project description:Global mRNA expression profiling of patient derived pancreatic carcinoma xenograft Bo63 following JQ1-SAHA combination therapy
| PRJNA272137 | ENA
Project description:Global mRNA expression profiling of patient derived pancreatic carcinoma xenograft Bo63 were collected using Agilent human whole genome array (G4845A AMADID 026652, cRNA 4x44k V2) . Two different sources of RNA were analyzed: 1.) Bo63 xenograft tumors grown on nude mice treated with vehicle only as control. 2.) Bo63 xenograft tumor grown on nude mice treated with JQ1 and SAHA (SAHA 25 mg/kg 1-0-0 and JQ1 50 mg/kg 0-0-1, treatment was imitated when tumor size reached 200 mm³ +/- 20 mm³. Two conditions (vehicle vs JQ1-SAHA treatment), each condition is represented by 3-4 biological replicates
2015-09-20 | E-GEOD-64837 | biostudies-arrayexpress
Project description:Oncogenic KRAS induces metabolic rewiring in pancreatic adenocarcinoma (PDAC) characterized, in part, by dependency on de novo pyrimidine biosynthesis. Pharmacologic inhibition of dihydroorotate dehydrogenase (DHODH), an enzyme in the de novo pyrimidine synthesis pathway, delays pancreatic tumor growth; however, limited monotherapy efficacy suggests that compensatory pathways may drive resistance. Here, we use an integrated metabolomic, proteomic and in vitro and in vivo DHODH inhibitor-anchored genetic screening approach to identify compensatory pathways to DHODH inhibition (DHODHi) and targets for combination therapy strategies. We demonstrate that DHODHi alters the apoptotic regulatory proteome thereby enhancing sensitivity to inhibitors of the anti-apoptotic BCL2L1 (BCL-XL) protein. Co-targeting DHODH and BCL-XL synergistically induces apoptosis in PDAC cells and patient-derived organoids. The combination of DHODH inhibition with Brequinar and BCL-XL degradation by DT2216, a proteolysis targeting chimera (PROTAC), significantly inhibits PDAC tumor growth. These data define mechanisms of adaptation to DHODHi and support combination therapy targeting BCL-XL in PDAC.
2025-04-09 | MSV000097577 | MassIVE
Project description:The elucidation of therapy-induced changes to the class I major histocompatibility complex (MHC-I)-bound tumor antigens is crucial for understanding immune-mediated tumor eradication and identifying potential targets for peptide vaccines to enhance the efficacy of immunotherapies. Here, we investigated how oncolytic reovirus therapy with and without immune checkpoint blockade (ICB) alters the tumor peptide-MHC repertoire. Using mass spectrometry analysis of immunoaffinity purified MHC peptides, we first showed that changes to the MHC immunopeptidome following reovirus treatment is cancer type-dependent, where a murine fibrosarcoma model displayed quantitative and qualitative variance in differentially expressed peptides (DEPs) as compared to those identified in a murine ovarian cancer model. We then determined that the combination therapy of reovirus and ICB in the fibrosarcoma model resulted in higher numbers of DEPs relative to either monotherapy alone. Most importantly, we identified reovirus and ICB-induced MHC peptides that are biologically active in stimulating interferon-gamma response in cognate CD8+ T cells, which likely contribute to cancer immunoediting. These findings highlight the importance of therapy-induced changes to the MHC immunopeptidome in shaping the underlying anti-tumor immune responses during reovirus and ICB combination therapy.
2021-12-06 | PXD024369 | Pride
Project description:Global mRNA expression profiling of patient derived pancreatic carcinoma xenograft Bo63 were collected using Agilent human whole genome array (G4845A AMADID 026652, cRNA 4x44k V2) . Two different sources of RNA were analyzed: 1.) Bo63 xenograft tumors grown on nude mice treated with vehicle only as control. 2.) Bo63 xenograft tumor grown on nude mice treated with JQ1 and SAHA (SAHA 25 mg/kg 1-0-0 and JQ1 50 mg/kg 0-0-1, treatment was imitated when tumor size reached 200 mm³ +/- 20 mm³.
2015-09-20 | GSE64837 | GEO
Project description:SAHA/JQ1 reduces in vivo tumorigenesis and proliferation of KP sarcoma cells. This model recapitulates human undifferentiated pleomporphic sarcoma (UPS). We used microarrays to investigate changes in global gene expression in response to these drugs.
2018-03-01 | GSE109923 | GEO
Project description:To investigate the immunomodulatory effects of IL-1R1 blockade in pancreatic ductal adenocarcinoma (PDAC), we performed bulk RNA sequencing of tumors subjected to distinct treatment regimens. Tumors were treated with either an anti–IL-1R1 antibody or left untreated, and another cohort received combination therapy with agonistic CD40 and anti–IL-1R1 antibodies versus CD40 agonist monotherapy. Gene ontology enrichment analysis of differentially expressed genes (p ≤ 0.05) revealed that anti–IL-1R1 treatment upregulated genes involved in RNA processing, including spliceosome-associated pathways, compared with untreated controls. Conversely, immune-related pathways—such as response to type II interferon, leukocyte-mediated immunity, and T-cell activation—were significantly downregulated in the anti–IL-1R1 group. In contrast, tumors receiving combination therapy exhibited enhanced innate and adaptive immune signatures compared to CD40 monotherapy, including antigen presentation, lymphocyte-mediated immunity, and regulation of immune effector functions. Metabolic pathways were notably downregulated in the combination group. Gene set enrichment analysis further confirmed the upregulation of key immune pathways, including NOD-like receptor signaling, NF-κB signaling, NK cell–mediated cytotoxicity, and JAK-STAT signaling, in the combination therapy group. These findings highlight the context-dependent effects of IL-1R1 blockade and support its synergistic potential with CD40 agonism in modulating the PDAC tumor microenvironment.
2025-07-25 | GSE301673 | GEO
Project description:Transcriptomics analysis to understand both efficacy and side effects of a cholesterol lowering drug combination therapy based on biological pathways and molecular processes affected by each drug alone or in combination. We have treated ApoE*3Leiden mice, a humanized atherosclerosis model with a unique human-like response to cholesterol-lowering drugs, with RSV and EZE alone and in combination. We demonstrate that processes affected by monotherapy can be retained and enhanced by combination therapy. In addition, combination therapy also affects a number of processes which are not predictable on basis of monotherapy M-bM-^@M-^S at least when analysis is performed within the borders of statistical significance. Our data however provide clues for these M-bM-^@M-^\non-predictableM-bM-^@M-^] effects. Total RNA obtained from mouse liver from mice treated with High-Cholesterol (HC) diet as control (n=8) or HC+RSV (n=8) or HC+EZE (n=8) or HC+RSV+EZE (n=8).
2013-02-27 | E-GEOD-38688 | biostudies-arrayexpress