Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA272138 | ENA |
REPOSITORIES: ENA
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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: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: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
Project description:Pancreatic ductal adenocarcinoma (PDAC) is a nearly uniformly lethal malignancy, with most patients facing an adverse clinical outcome. Given the pivotal role of aberrant Notch signaling in the initiation and progression of PDAC, we investigated the effect of MRK-003, a potent and selective γ-secretase inhibitor, in preclinical PDAC models. We used a panel of human PDAC cell lines, as well as patient-derived PDAC xenografts, to determine whether pharmacological targeting of the Notch pathway could inhibit pancreatic tumor growth and potentiate gemcitabine sensitivity. In vitro, MRK-003 treatment downregulated the canonical Notch target gene Hes-1, significantly inhibited anchorage independent growth, and reduced the subset of CD44+CD24+ and aldehyde dehydrogenase (ALDH)+ cells that have been attributed with tumor initiating capacity. Ex vivo pretreatment of PDAC cells with MRK-003 in culture significantly inhibited the subsequent engraftment in immunocompromised mice. In vivo, MRK-003 monotherapy significantly blocked tumor growth in 5 of 9 (56%) patient-derived PDAC xenografts. Moreover, a combination of MRK-003 and gemcitabine showed enhanced antitumor effects compared to gemcitabine alone in 4 of 9 (44%) PDAC xenografts. Baseline gene expression analysis of the treated xenografts indicated that upregulation of nuclear factor kappa B (NFκB) pathway components was associated with the sensitivity to single MRK-003, while upregulation in B-cell receptor (BCR) signaling and nuclear factor erythroid-derived 2-like 2 (NRF2) pathway correlated with response to the combination of MRK-003 with gemcitabine. The preclinical findings presented here provide further rationale for small molecule inhibition of Notch signaling as a therapeutic strategy in PDAC. Pancreatic ductal adenocarcinoma xenografts were grown in Athymic Nude-Foxn1nu mice. RNA was extracted and profiled in Affymetrix platform to identify genes correlating with sensitivity to MRK-003
2012-05-02 | E-GEOD-37645 | biostudies-arrayexpress
Project description:Improvement of pancreatic ductal adenocarcinoma (PDAC) patients’ outcomes require exploration of novel therapeutic mechanisms. Thus far, most studies of PDAC therapies, including those inhibiting small ubiquitin-like modifications (SUMOylation), have focused on PDAC epithelial cell biology. The mechanisms by which SUMOylation impacts PDAC in the context of its tumor microenvironment (TME) are poorly understood. We used clinically relevant orthotopic PDAC mouse models to investigate the effect of SUMOylation inhibition using a specific, clinical stage compound, TAK-981. TAK-981 monotherapy improved survival in immunocompetent mice. However, in contrast to its inhibition of PDAC cell proliferation in vitro, the survival benefit of TAK-981 in vivo is dependent on the presence of T cells. Induction of adaptive anti-tumor immunity is the dominant anti-tumor effect of SUMOylation inhibition in vivo. To elucidate the mechanism of adaptive immunity, we performed comparative single cell transcriptomics analyses of murine and human PDAC tumors, including cancer cells, T cells, tumor associated macrophages (TAM) and cancer associated fibroblasts (CAF), in combination with immunofluorescence, immunohistochemistry, western blots and qPCR. Mechanistically, SUMOylation regulates T cell activation and differentiation. In addition, TAK-981 changed gene expression in TAM, CAF and cancer cells that are likely to enhance the anti-tumor T cell response. These findings provide rationale for combination strategies to augment adaptive immune responses to PDAC that are necessary for durable disease control in PDAC patients.
2024-09-02 | GSE212446 | GEO