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Mus musculus
4 Downloadable Samples
Description
Endothelial inflammation contributes to the pathogenesis of numerous human diseases; however, the role of tumor endothelial inflammation in the growth of experimental tumors and its influence on the prognosis of human cancers is less understood. TNF-, an important mediator of tumor stromal inflammation, is known to target the tumor vasculature. In this study, we demonstrate that B16-F1 melanomas grew more rapidly in C57BL/6 wild-type (WT) mice than in syngeneic mice with germline deletions of both TNF- receptors (KO). This enhanced tumor growth was associated with increased COX2 inflammatory expression in WT tumor endothelium compared to endothelium in KO mice. We purified endothelial cells from WT and KO tumors and characterized dysregulated gene expression, which ultimately formed the basis of a 6-gene Inflammation-Related Endothelial-derived Gene (IREG) signature. This inflammatory signature expressed in WT tumor endothelial cells was trained in human cancer datasets and predicted a poor clinical outcome in breast cancer, colon cancer, lung cancer and glioma. Consistent with this observation, conditioned media from human endothelial cells treated with pro-inflammatory cytokines (TNF- and interferons) accelerated the growth of human colon and breast tumors in immune-deprived mice as compared with conditioned media from untreated endothelial cells. These findings demonstrate that activation of endothelial inflammatory pathways contributes to tumor growth and progression in diverse human cancers.
Publication Title
Tumor endothelial inflammation predicts clinical outcome in diverse human cancers.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 11 Downloadable Samples
Description
Background: Microvascular injury and increased vascular leakage are prominent features of the radiation-induced lung injury (RILI) which follows cancerassociated thoracic irradiation. The mechanisms of RILI are incompletely understood and therapeutic strategies to limit RILI are currently unavailable. We established a murine model of radiation pneumonitis in order to assess mechanism-based therapies for RILI-induced inflammation and vascular barrier dysfunction. Based on prior studies, we investigated the therapeutic potential of simvastatin as a vascular barrier protective agent in RILI.
Publication Title
Simvastatin attenuates radiation-induced murine lung injury and dysregulated lung gene expression.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 10 Downloadable Samples
Description
Gene expression profile of joint tissue from C3H and interval specific congenic mouse lines (ISCL) following infection with Borrelia burgdorferi
Publication Title
Interval-specific congenic lines reveal quantitative trait Loci with penetrant lyme arthritis phenotypes on chromosomes 5, 11, and 12.
Sample Metadata Fields
Specimen part
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GSE30747- Mus musculus
- 28 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
An integrated approach to dissecting oncogene addiction implicates a Myb-coordinated self-renewal program as essential for leukemia maintenance.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 16 Downloadable Samples
Description
To explore oncogene addiction programs in a genetically defined leukemia context we developed an AML mouse model driven by a conditional MLL-AF9 allele together with oncogenic Ras, which enabled us to examine the consequences of MLL-AF9 inhibition in established disease. In order to produce a tightly regulated system that was easy to monitor, we constructed two retroviral vectors containing dsRed-linked MLL-AF9 under control of a tetracycline response element promoter, and KrasG12D or NrasG12D linked to the Tet-off tet-transactivator, which activates TRE expression in a doxycycline repressible manner. Leukemias were generated by retroviral cotransduction of both vectors into hematopoietic stem and progenitor cells, which were transplanted into syngeneic mice. Cells harboring both constructs induced aggressive myelomonocytic leukemia. Five independent primary leukemia cell lines were established from bone marrow of terminal mice. Treatment of these lines with doxycycline rapidly turned off MLL-AF9 expression, and induced terminal myeloid differentiation and complete disease remission in vivo.
Publication Title
An integrated approach to dissecting oncogene addiction implicates a Myb-coordinated self-renewal program as essential for leukemia maintenance.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
Description
Using an integrative approach combining a Tet-off conditional AML mouse model, global expression profiling following suppression of the driving MLL-AF9 oncogene, and a new Tet-on conditional shRNA expression system we have identified Myb as critical mediator of addiction to MLL-AF9. Suppression of Myb in established AML in vivo terminates aberrant self-renewal and triggers a terminal myeloid differentiation program that precisely phenocopies the effects of suppressing MLL-AF9. Remarkably, suppressing Myb effectively eradicates aggressive and chemotherapy resistant AML.
Publication Title
An integrated approach to dissecting oncogene addiction implicates a Myb-coordinated self-renewal program as essential for leukemia maintenance.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 3 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Epigenetic chromatin states uniquely define the developmental plasticity of murine hematopoietic stem cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 3 Downloadable Samples
Description
An investigation of the global gene expression signatures of murine hematopoietic stem cell differentiation during steady state hematopoiesis.
Publication Title
Epigenetic chromatin states uniquely define the developmental plasticity of murine hematopoietic stem cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 35 Downloadable Samples
Description
Although mast cells elicit proinflammatory and type I IFN responses upon VSV infection, in response to L.monocytogenes (L.m) or S. Typhimurium (S.t), such cells elicit a transcriptional program devoid of type I IFN response.
Publication Title
Mast cells elicit proinflammatory but not type I interferon responses upon activation of TLRs by bacteria.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
Description
Lactobacilli are probiotics that, among other health promoting effects, have been ascribed immunostimulating and virus preventive properties. Certain lactobacilli species have been shown to possess strong IL-12 inducing properties. As IL-12 production depends on the up-regulation of type I interferons, we hypothesized that the strong IL-12 inducing capacity of L. acidophilus NCFM in murine bone marrow derived DC is caused by an up-regulation of IFN-, which subsequently stimulates the induction of IL-12 and the dsRNA binding toll like receptor (TLR)-3. The expression of the genes encoding IFN-, IL-12, IL-10 and TLR-3 in DC upon stimulation with L. acidophilus NCFM was measured. L. acidophilus NCFM induced a much stronger expression of ifn-, il-12 and il-10 compared to the synthetic dsRNA ligand Poly I:C, whereas the levels of expressed tlr-3 were similar. By the use of whole genome microarray gene expression, we investigated whether other genes related to the viral defence were up-regulated in DC upon stimulation with L. acidophilus NCFM and found that various virus defence related genes, both early and late, were among the strongest up-regulated genes. The IFN- stimulating capability was also detected in another L. acidophilus strain, but was not a property of other probiotic bacteria tested (B. bifidum and E. coli nissle).The IFN- inducing capacity was markedly reduced in TLR-2 -/- DCs, dependent on endocytosis and the major cause of the induction of il-12 and tlr-3 in L. acidophilus NCFM stimulated cells. Collectively, our results reveal that certain lactobacilli trigger the expression of viral defence genes in DC in a TLR-2 manner through induction of IFN- .
Publication Title
Lactobacillus acidophilus induces virus immune defence genes in murine dendritic cells by a Toll-like receptor-2-dependent mechanism.
Sample Metadata Fields
Treatment, Time
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