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GSE26308
Mus musculus, Homo sapiens
3 Downloadable Samples
Description
5,6-Dimethylxanthenone-4-acetic acid (DMXAA), a tumor vascular disrupting agent, is shown here to have substantial activity as a single agent against human A375 melanoma xenografts in nude mice (94 % hemorrhagic necrosis after 24 h, and 26 days growth delay following single dose at 25 mg/kg). CD45+ cells in tumor tissue increased 5-fold over the first 3 days after treatment, which was due largely to an influx of CD11b+ Ly6G+ neutrophils. Using murine and human multiplex cytokine assays to dissect the cytokines produced by host stromal cells or by the melanoma cells, it was shown that both the stromal cells and the A375 melanoma cells produced cytokines capable of attracting neutrophils into the tumor. The same xenografts were also analyzed using human and mouse Affymetrix microarrays to separately identify tumor cell-specific (human) and stromal cell-specific (mouse) gene expression changes. DMXAA induced numerous stromal cytokine mRNAs, including IP-10, IL-6, MIP-1/, MIP-2, KC, RANTES, MIG, MCP-1 and IL-1, many of which were also elevated at the protein level. Numerous human cytokine mRNAs were also induced including MCP-1, IL-8, GRO, VEGF, GM-CSF and IL-6, which again was in line with our protein data. Pathway analysis indicated that significant numbers of the stromal mRNAs induced by DMXAA are regulated downstream of TNF-, interferon- and NFB. Our results suggest that DMXAA may have utility in combination therapy for human melanoma through the activation of pro-inflammatory signalling pathways and cytokine expression from both stromal and tumor cells, leading to haemorrhagic necrosis, neutrophil influx and growth inhibition.
Publication Title
Dissection of stromal and cancer cell-derived signals in melanoma xenografts before and after treatment with DMXAA.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
Illumina NovaSeq 6000
Description
Cigarette smoke (CS) is one of risk factor to chronic obstructive pulmonary disease that is the major causes of death in the world. Furthermore, CS is an independent risk factor for chronic kidney disease (CKD) in the general adult population. The goal of this project was to identified the mechanisms of renal damage that might be associated with exposure to CS extract (CSE) in human kidney proximal tubular epithelial cell line (HK-2 cells) cells. Overall design: RNA sequencing of human kidney proximal tubular epithelial cell line (HK-2 cells) after 24 hours exposure to 0.6% CSE.
Publication Title
Cigarette Smoke Exposure Increases Glucose-6-phosphate Dehydrogenase, Autophagy, Fibrosis, and Senescence in Kidney Cells In Vitro and In Vivo.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
Description
Mamamlian cardiogenesis occurs through the development of discreate populations of first and second heart field progenitors. We have used a dual transgenic color reproter system to isolate purified populations of these progenitors.
Publication Title
Generation of functional ventricular heart muscle from mouse ventricular progenitor cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus, Homo sapiens
- 25 Downloadable Samples
Description
MicroRNAs have emerged as major genetic elements in the genesis and suppression of cancer. Here, multi-dimensional cancer genome analysis and validation has defined a novel Glioblastoma Multiforme (GBM) tumor suppressor pathway and mechanism of action centered on Quaking (QK), a member of the STAR family of RNA-binding proteins. Combined functional, biochemical and computational studies establish that p53 directly regulates QK gene expression, QK protein binds and stabilizes miR-20a of the cancer-relevant miR-17-92 cluster, and miR-20a in turn functions to regulate TGFR2 and the TGF signaling network. Linkage of these pathway components is supported by their genome and expression status across GBM specimens and by their gain- and loss-of-function interactions in in vitro and in vivo complementation studies. This p53-QK-miR-20a axis expands our understanding of the p53 tumor suppression network in cancer and reveals a novel tumor suppression mechanism involving regulation of specific cancer-relevant microRNAs.
Publication Title
STAR RNA-binding protein Quaking suppresses cancer via stabilization of specific miRNA.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 14 Downloadable Samples
Description
Activated phosphoinositide 3-kinase (PI3K)-AKT signaling appears to be an obligate event in the development of cancer. The highly related members of the mammalian FoxO transcription factor family, FoxO1, FoxO3, and FoxO4, represent one of several effector arms of PI3K-AKT signaling, prompting genetic analysis of the role of FoxOs in the neoplastic phenotypes linked to PI3K-AKT activation. While germline or somatic deletion of up to five FoxO alleles produced remarkably modest neoplastic phenotypes, broad somatic deletion of all FoxOs engendered a progressive cancer-prone condition characterized by thymic lymphomas and hemangiomas, demonstrating that the mammalian FoxOs are indeed bona fide tumor suppressors. Transcriptome and promoter analyses of differentially affected endothelium identified direct FoxO targets and revealed that FoxO regulation of these targets in vivo is highly context-specific, even in the same cell type. Functional studies validated Sprouty2 and PBX1, among others, as FoxO-regulated mediators of endothelial cell morphogenesis and vascular homeostasis.
Publication Title
FoxOs are lineage-restricted redundant tumor suppressors and regulate endothelial cell homeostasis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
Description
Identify potential QK-regulated mRNAs and linked pathways by comparing the transcriptional profiles of shGFP- and shQK-transduced Ink4a/Arf-/- Pten-/- primary mouse astrocytes
Publication Title
STAR RNA-binding protein Quaking suppresses cancer via stabilization of specific miRNA.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
Description
Identify potential miR-20a regulated mRNAs and linked pathways in the setting of QK knockdown by comparing the transcriptional profiles of shQK-transduced primary mouse Ink4a/Arf-/- Pten-/- astrocytes together with miR-20a or a scrambled miRNA control (miR-NT)
Publication Title
STAR RNA-binding protein Quaking suppresses cancer via stabilization of specific miRNA.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
Description
FoxOs cooperatively regulate diverse pathways governing neural stem cell homeostasis
Publication Title
FoxOs cooperatively regulate diverse pathways governing neural stem cell homeostasis.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 4 Downloadable Samples
Description
Glioblastoma (GBM) is a highly lethal brain tumor presenting as one of two subtypes with distinct clinical histories and molecular profiles. The primary GBM subtype presents acutely as high-grade disease that typically harbors EGFR, PTEN and Ink4a/Arf mutations, and the secondary GBM subtype evolves from the slow progression of low-grade disease that classically possesses PDGF and p53 events1. Here, we show that concomitant CNS-specific deletion of p53 and Pten in the mouse CNS generates a penetrant acute-onset high-grade malignant glioma phenotype with striking clinical, pathological and molecular resemblance to primary GBM in humans. This genetic observation prompted p53 and PTEN mutational analysis in human primary GBM, demonstrating unexpectedly frequent inactivating mutations of p53 as well the expected PTEN mutations. Integrated transcriptomic profling, in silico promoter analysis and functional studies of murine neural stem cells (NSCs) established that dual, but not singular, inactivation of p53 and Pten promotes an undifferentiated state with high renewal potential and drives elevated c-Myc levels and its associated signature. Functional studies validated increased c-Myc activity as a potent contributor to the impaired differentiation and enhanced renewal of p53-Pten null NSCs as well as tumor neurospheres (TNSs) derived from this model. c-Myc also serves to maintain robust tumorigenic potential of p53-Pten null TNSs. These murine modeling studies, together with confirmatory transcriptomic/promoter studies in human primary GBM, validate a pathogenetic role of a common tumor suppressor mutation profile in human primary GBM and establish c-Myc as a key target for cooperative actions of p53 and Pten in the regulation of normal and malignant stem/progenitor cell differentiation, self-renewal and tumorigenic potential.
Publication Title
p53 and Pten control neural and glioma stem/progenitor cell renewal and differentiation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 15 Downloadable Samples
Description
We used microarrays to detail the global gene expression and identified differentially expressed gene list between wild-type anterior prostates and Ptenpc-/- anterior prostates, Ptenpc-/-Smad4pc-/- and Ptenpc-/- anterior prostates, Ptenpc-/-p53pc-/- and Ptenpc-/- anterior prostates at 15 weeks of age.
Publication Title
SMAD4-dependent barrier constrains prostate cancer growth and metastatic progression.
Sample Metadata Fields
Age, Specimen part
View Samples