Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA338687 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Rational selection of syngeneic preclinical tumor models for immunotherapeutic drug discovery
| PRJNA338671 | ENA
Project description:Rational selection of syngeneic preclinical tumor models for immunotherapeutic drug discovery [aCGH]
| PRJNA338686 | ENA
Project description:Characterisation of murine syngeneic tumor models enables rational preclinical model selection for immuno-oncology drug discovery
| PRJEB12925 | ENA
Project description:Murine syngeneic tumor models are the cornerstone of novel immuno-oncology (IO)-based therapy development but the molecular and immunological features of these models are still not clearly defined. The translational relevance of differences between the models is not fully understood, impeding appropriate preclinical model selection for target validation, and ultimately hindering drug development. Within a panel of commonly-used murine syngeneic tumor models, we showed variable responsiveness to IO-therapies. We employed aCGH, whole-exome sequencing, exon microarray analysis and flow cytometry to extensively characterise these models and revealed striking differences that may underlie these contrasting response profiles. We identified strong differential gene expression in immune-related pathways and changes in immune cell-specific genes that suggested differences in tumor immune infiltrates between models. We further investigated this using flow cytometry, which showed differences in both the composition and magnitude of the tumor immune infiltrates, identifying models that harbor ‘inflamed’ and ‘non-inflamed’ tumor immune infiltrate phenotypes. Moreover, we found that immunosuppressive cell types predominated in syngeneic mouse tumor models that did not respond to immune-checkpoint blockade, whereas cytotoxic effector immune cells were enriched in responsive models. A cytotoxic cell-rich tumor immune infiltrate has been correlated with increased efficacy of IO-therapy in the clinic and these differences could underlie the varying response profiles to IO-therapy between the syngeneic models. This characterisation highlighted the importance of extensive profiling and will enable investigators to select appropriate models to interrogate the activity of IO-therapies as well as combinations with targeted therapies in vivo.
2016-12-07 | GSE85508 | GEO
Project description:Murine syngeneic tumor models are the cornerstone of novel immuno-oncology (IO)-based therapy development but the molecular and immunological features of these models are still not clearly defined. The translational relevance of differences between the models is not fully understood, impeding appropriate preclinical model selection for target validation, and ultimately hindering drug development. Within a panel of commonly-used murine syngeneic tumor models, we showed variable responsiveness to IO-therapies. We employed aCGH, whole-exome sequencing, exon microarray analysis and flow cytometry to extensively characterise these models and revealed striking differences that may underlie these contrasting response profiles. We identified strong differential gene expression in immune-related pathways and changes in immune cell-specific genes that suggested differences in tumor immune infiltrates between models. We further investigated this using flow cytometry, which showed differences in both the composition and magnitude of the tumor immune infiltrates, identifying models that harbor ‘inflamed’ and ‘non-inflamed’ tumor immune infiltrate phenotypes. Moreover, we found that immunosuppressive cell types predominated in syngeneic mouse tumor models that did not respond to immune-checkpoint blockade, whereas cytotoxic effector immune cells were enriched in responsive models. A cytotoxic cell-rich tumor immune infiltrate has been correlated with increased efficacy of IO-therapy in the clinic and these differences could underlie the varying response profiles to IO-therapy between the syngeneic models. This characterisation highlighted the importance of extensive profiling and will enable investigators to select appropriate models to interrogate the activity of IO-therapies as well as combinations with targeted therapies in vivo.
2016-12-07 | GSE85507 | GEO
Project description:While taxane-platin standard chemotherapy provides benefit in advanced and localized non-small cell lung cancer (NSCLC), the majority of patients relapse with drug resistant tumors. Mechanisms underlying NSCLC resistance to this standard doublet chemotherapy are still not fully understood, and treatment options for chemoresistant lung tumors are limited. The goals of this work were to establish new preclinical NSCLC models of resistance to taxane-platin doublet chemotherapy, identify mechanisms of resistance, and develop new rational pharmacologic approaches to target drug resistant NSCLCs.
2016-12-31 | GSE77209 | GEO
Project description:Many preclinical therapy studies have focused on a small number of well-described mouse allograft or human xenograft models that poorly represent the heterogeneity of human disease. Here we have assembled a panel of mouse mammary cell lines that metastasize in syngeneic mouse hosts and we have assessed gene expression programs in the untreated primary tumors with the goal of generating information that may be useful to the identification of biomarkers that predict response to therapeutic intervention. We used microarrays to assess global gene expression programs in primary tumors from 12 metastatic mouse mammary tumor models transplanted orthotopically into syngeneic, fully immunocompetent mouse hosts. The 12 tumor models used here are based on published cell lines that had been established from either spontaneous mammary tumors or from mammary tumors arising in genetically engineered mouse models. All cell lines were previously described to be metastatic. Cells were surgically implanted in the #4 mammary fat pads of syngeneic mice and primary tumors were harvested when they reached 0.5-1.0 cm diameter and snap-frozen for later RNA extraction. 4 independent tumors were collected for each of the 12 models.
2015-05-19 | E-GEOD-69006 | biostudies-arrayexpress
Project description:The cell line-derived xenografts and patient derived xenografts have limited use in cancer immunotherapy evaluation because an immune compromised host is required for xenotransplantation. Syngeneic mouse models are derived by transplanting established mouse cell lines or tumor tissues to strain matched mouse hosts, which are better suited to study the interplay between immune and tumor cells. We investigated the differences as well as similarities of a panel of ten mouse syngeneic models to features of human tumors by proteomics, which will provide valuable information to assist experimental biologists in model selection.
2019-12-03 | PXD011885 | Pride
Project description:This study evaluates mechanisms of glycaemic stress underpinning cardiovascular risk in diabetes. Using in vitro and in vivo models, we demonstrate that glycaemic variability rather than hyperglycaemia alone is a dominant risk factor for heart muscle dysfunction and myocardial injury sensitivity in diabetes. These findings provide new preclinical models for mechanistic and drug discovery studies and inform strategies for managing cardiovascular outcomes in patients with diabetes.
2025-12-14 | GSE279917 | GEO
Project description:BIOMEDE (NCT02233049) was a phase II, biopsy-driven clinical trial in DIPG patients with randomisation of stratification between dasatinib, erlotinib and everolimus. Methylation array profiling was carried out alongside drug screening in newly-established patient-derived models of DIPG in vitro and in vivo. Alongside exome, RNAseq, phospho-proteomics, these data highlight the MAPK pathway as a therapeutic target in DIPG, and show the importance of parallel resistance modelling and rational combinatorial treatment
2020-08-31 | E-MTAB-9282 | biostudies-arrayexpress