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GSE40564
Homo sapiens
9 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Purpose: The phosphoinositide 3-kinase (PI3K) pathway is fundamental for cell proliferation and survival and is frequently altered and activated in neoplasia, including carcinomas of the lung. In this study we investigated the potential of targeting the catalytic class IA PI3K isoforms in small cell lung cancer (SCLC), which is the most aggressive of all lung cancer types. Experimental Design: The expression of PI3K isoforms in patient specimens was analyzed. The effects on SCLC cell survival and downstream signaling were determined following PI3K isoform inhibition by selective inhibitors or down-regulation by small interfering RNA. Results: Over-expression of the PI3K isoforms p110 and p110 was shown by immunohistochemistry in primary SCLC tissue samples. Targeting the PI3K p110 with RNA interference (RNAi) or selective pharmacological inhibitors resulted in strongly affected cell proliferation of SCLC cells in vitro and in vivo, while targeting p110 was less effective. Inhibition of p110 also resulted in increased apoptosis and autophagy, which was accompanied by decreased phosphorylation of Akt and components of the mammalian target of rapamycin (mTOR) pathway, such as the ribosomal S6 protein, and the eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1). A DNA microarray analysis revealed that p110 inhibition profoundly affected the balance of pro- and anti-apoptotic Bcl-2 family proteins. Finally, p110 inhibition led to impaired SCLC tumor formation and vascularization in vivo. Conclusion: Together our data demonstrate the key involvement of the PI3K isoform p110 in multiple tumor-promoting processes in SCLC.
Publication Title
Targeting the phosphoinositide 3-kinase p110-α isoform impairs cell proliferation, survival, and tumor growth in small cell lung cancer.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 97 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The concept of tumor stem cells (TSCs) provides a new paradigm for understanding tumor biology, although it remains unclear whether TSCs will prove to be a more robust model than traditional cancer cell lines. We demonstrate marked phenotypic and genotypic differences between primary human tumor-derived TSCs and their matched glioma cell lines. TSCs derived directly from primary glioblastomas harbor extensive similarities to normal NSC and recapitulate the genotype, gene expression patterns and in vivo biology of human glioblastomas. By contrast, the matched, traditionally grown tumor cell lines do not secondary to in vitro genomic alterations. These findings suggest that TSCs may be a more reliable model than many commonly utilized cancer cell lines for understanding the biology of primary human tumors. Analysis of gene expression data is described in Lee et al., Cancer Cell, 2006.
Publication Title
Tumor stem cells derived from glioblastomas cultured in bFGF and EGF more closely mirror the phenotype and genotype of primary tumors than do serum-cultured cell lines.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus, Homo sapiens
- 32 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gliomas are mostly incurable secondary to their diffuse infiltrative nature. Thus, specific therapeutic targeting of invasive glioma cells is an attractive concept. As cells exit the tumor mass and infiltrate brain parenchyma, they closely interact with a changing micro-environmental landscape that sustains tumor cell invasion.
Publication Title
Identification of molecular pathways facilitating glioma cell invasion in situ.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 577 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This is Rembrandt gene expression data (Affymetrix HG-U133Plus2).
Publication Title
Rembrandt: helping personalized medicine become a reality through integrative translational research.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Transcriptome analysis of growth hormone dependant genes in glomerular podocytes
Publication Title
Growth hormone (GH)-dependent expression of a natural antisense transcript induces zinc finger E-box-binding homeobox 2 (ZEB2) in the glomerular podocyte: a novel action of gh with implications for the pathogenesis of diabetic nephropathy.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 24 Downloadable Samples
Affymetrix Murine Genome U74B Version 2 Array (mgu74bv2), Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Analyses of six Ts1Cje (Down syndrome) and six normal littermate (2N) mouse brains at postnatal day 0.
Publication Title
Dosage-dependent over-expression of genes in the trisomic region of Ts1Cje mouse model for Down syndrome.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Analyses of six Ts1Cje (Down syndrome) and six normal littermate (2N) mouse brains at postnatal day 0.
Publication Title
Dosage-dependent over-expression of genes in the trisomic region of Ts1Cje mouse model for Down syndrome.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Murine Genome U74B Version 2 Array (mgu74bv2), Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Analyses of six Ts1Cje (Down syndrome) and six normal littermate (2N) mouse brains at postnatal day 0.
Publication Title
Dosage-dependent over-expression of genes in the trisomic region of Ts1Cje mouse model for Down syndrome.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 31 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We developed a computational framework that integrates chromosomal copy number and gene expression data for detecting aberrations that promote cancer progression. We demonstrate the utility of this framework using a melanoma dataset. Our analysis correctly identified known drivers of melanoma and predicted multiple novel tumor dependencies. Two dependencies, TBC1D16 and RAB27A, confirmed empirically, suggest that abnormal regulation of protein trafficking contributes to proliferation in melanoma. Together, these results demonstrate the ability of integrative Bayesian approaches to identify novel candidate drivers with biological, and possibly therapeutic, importance in cancer.
Publication Title
An integrated approach to uncover drivers of cancer.
Sample Metadata Fields
Cell line
View Samples- Mus musculus, Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
An important question for the use of the mouse as a model for studying human disease is the degree of functional conservation of genetic control pathways from human to mouse. The human placenta and mouse placenta show structural similarities but there has been no systematic attempt to assess their molecular similarities or differences. We built a comprehensive database of protein and microarray data for the highly vascular exchange region micro-dissected from the human and mouse placenta near-term. Abnormalities in this region are associated with two of the most common and serious complications of human pregnancy, maternal preeclampsia (PE) and fetal intrauterine growth restriction (IUGR), each disorder affecting ~5% of all pregnancies.
Publication Title
Comparative systems biology of human and mouse as a tool to guide the modeling of human placental pathology.
Sample Metadata Fields
No sample metadata fields
View Samples