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GSE13330
Homo sapiens
16 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Alterations in the tissue microenvironment collaborate with cell autonomous genetic changes to contribute to neoplastic progression. The importance of the microenvironment in neoplastic progression is underscored by studies demonstrating that fibroblasts isolated from a tumor stimulate the growth of preneoplastic and neoplastic cells in xenograft models. Similarly, senescent fibroblasts promote preneoplastic cell growth in vitro and in vivo. Because senescent cells accumulate with age, their presence is hypothesized to facilitate preneoplastic cell growth and tumor formation in older individuals. To identify senescent stromal factors directly responsible for stimulating preneoplastic cell growth, we carried out whole genome transcriptional profiling and compared senescent fibroblasts to their younger counterparts. We identified osteopontin (OPN) as one of the most highly elevated transcripts in senescent fibroblasts. Importantly, reduction of OPN protein levels by RNAi did not impact senescence induction in fibroblasts; however, it dramatically reduced the growth-promoting activities of senescent fibroblasts in vitro and in vivo, demonstrating that OPN is necessary for paracrine stimulation of preneoplastic cell growth. In addition, we found that recombinant OPN was sufficient to stimulate preneoplastic cell growth. Finally, we demonstrate that OPN is expressed in senescent stroma within preneoplastic lesions that arise following DMBA/TPA treatment of mice, suggesting that stromal-derived OPN-mediated signaling events impact neoplastic progression.
Publication Title
Senescent stromal-derived osteopontin promotes preneoplastic cell growth.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
Acadesine is a nucleoside analogue with known antileukemic effects in different neoplasms. We investigated the activity of acadesine ne exerts a cytotoxic effect in MCL and synergizes with rituximab supporting clinical examination of this strategy for MCL patients
Publication Title
Synergistic anti-tumor activity of acadesine (AICAR) in combination with the anti-CD20 monoclonal antibody rituximab in in vivo and in vitro models of mantle cell lymphoma.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
Phosphatidylinositol-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway activation contributes to mantle cell lymphoma (MCL) pathogenesis and drug resistance. However, the use of mTOR inhibitors as single agents have shown limited clinical efficacy in relation with drug activation of feedback loops. Selective PI3K inhibition or dual PI3K/mTOR catalytic inhibition are different therapeutic approaches developed to achieve effective pathway blockage. Here, we evaluated the antitumor activity of a mTOR inhibitor, a pan-PI3K inhibitor and a dual PI3K/mTOR inhibitor in primary MCL cells. We found that dual PI3K/mTOR inhibitor modulated angiogenesis, tumor invasiveness and cytokine signaling compared to a mTOR inhibitor and a pan-PI3K inhibitor in MCL.
Publication Title
Dual PI3K/mTOR inhibition is required to effectively impair microenvironment survival signals in mantle cell lymphoma.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
Double Hit Lymphoma (DHL) were treated with the BRD4 inhibitor 100 nM CPI203 for 6h
Publication Title
The BET bromodomain inhibitor CPI203 overcomes resistance to ABT-199 (venetoclax) by downregulation of BFL-1/A1 in in vitro and in vivo models of MYC+/BCL2+ double hit lymphoma.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
IGF-I exert multiple effects in different retinal cell populations in both physiological and pathological conditions. Transgenic mice overexpressing IGF-I in the retina showed impaired electroretinographic responses at 6-7 months of age that worsen with age. This retinal neuronal dysfunction was correlated with the loss of rod photoreceptors, bipolar, ganglion and amacrines cells. Neuronal alterations were preceded by the overexpression of retinal stress markers, acute phase proteins and gliosis-related genes. IGF-I overexpression leads to chronic gliosis and microgliosis in TgIGF-I retinas, with mild oxidative stress, impaired recycling of glutamate and defective potassium buffering. These impaired supportive functions can contribute to neurodegeneration in TgIGF-I retinas, together with the increased production of pro-inflammatory cytokines, potential mediators of neuronal death.
Publication Title
Insulin-like Growth Factor 2 Overexpression Induces β-Cell Dysfunction and Increases Beta-cell Susceptibility to Damage.
Sample Metadata Fields
Sex, Specimen part
View Samples- Danio rerio
- 54 Downloadable Samples
IlluminaHiSeq2000
Description
Development is a complex and well-defined process characterized by rapid cell proliferation and apoptosis. At this stage in life, a developmentally young organism is more sensitive to toxicants and other stressors when compared to an adult. In response to pro-oxidant exposure, members of the Cap’n’Collar (CNC) basic leucine zipper (b-ZIP) transcription factor family (including the Nfe2-related factors, Nrfs) activate the expression of genes that contribute to reduced toxicity. Here, we studied the role of the Nrf protein, Nfe2, in the developmental response to pro-oxidant exposure in the zebrafish. Following acute waterborne exposures to diquat or tert-buytlhydroperoxide (tBOOH) at three developmental stages, wildtype (WT) and nfe2 knockout (KO) embryos and larvae were morphologically scored and their transcriptomes sequenced. Overall design: Wildtype animals were on the AB background and an additional germline nfe2 knockout strain were created by disruption of the nfe2 reading frame. Waterborne exposures to either diquat or tBOOH were carried out at three different developmental stages: 2 hours post fertilization (hpf), 48hpf, and 96hpf in 3 pools of 30 embryos per condition. Animals were exposed to no treatment, 20µM diquat or 1mM tBOOH for a 4-hour dosing period. Total RNA was isolated from pooled animals and 50 bp, paired end, libraries were sequenced using the Illumina HiSeq 2000 platform, with approximately 25 million reads per sample. Reads were then aligned to the Ensembl GRCz10 zebrafish reference genome using Tophat2 and raw counts data normalized using DESeq2. Gene annotation was from Ensemble for GRCz10.
Publication Title
The transcription factor, Nuclear factor, erythroid 2 (Nfe2), is a regulator of the oxidative stress response during Danio rerio development.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The level of trypsin-2 has been shown to correlate with the malignancy and metastatic potential of many cancer.
Publication Title
Trypsin-2 enhances carcinoma invasion by processing tight junctions and activating ProMT1-MMP.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 64 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The genome of mantle cell lymphoma (MCL) is, in addition to the translocation t(11;14), characterized by a high number of secondary chromosomal gains and losses that likely account for the varying survival times of MCL patients. We investigated 77 primary MCL tumors with available clinical information using high resolution RNA expression and genomic profiling and applied our recently developed gene expression and dosage integrator (GEDI) algorithm to identify novel genes and pathways that may be of relevance for the pathobiology of MCL. We show that copy number neutral loss of heterozygosity (CNN-LOH) is common in MCL and targets regions that are frequently affected by deletions. The molecular consequences of genomic copy number changes appear complex, even in genomic loci with identified tumor suppressors, such as the region 9p21 containing the CDKN2A locus. Moreover, the deregulation of novel genes such as CUL4A, ING1 and MCPH1 may affect the two crucial pathogenetic mechanisms in MCL, the disturbance of the proliferation and DNA damage response pathways. Deregulation of the Hippo pathway may have a pathogenetic role in MCL, since decreased expression of its members MOBKL2A, MOBKL2B and LATS2 was associated with inferior outcome also in an independent validation series of 32 MCL.
Publication Title
Pathway discovery in mantle cell lymphoma by integrated analysis of high-resolution gene expression and copy number profiling.
Sample Metadata Fields
Disease, Disease stage, Subject
View Samples- Danio rerio
- 9 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
In this study, zebrafish ZF4 and PAC2 cells were seeded in 0.5% or 1% FCS, respectively, and grown to 85% confluence and subsequently cultured for 24 hours without serum. Then they were treated with either medium without serum or medium with serum (ZF4 in 10% FCS and PAC2 in 15% FCS).After 6 hours, RNA was extracted from the cells and analyzed using the Affymetrix GeneChip Zebrafish Genome Array (GeneChip 430). There are 15502 oligonucleotide sets on each Affymetrix chip, 14895 of which can be linked to a UniGene assignment (Unigene data set 06-12-2005).
Publication Title
Genetic and transcriptome characterization of model zebrafish cell lines.
Sample Metadata Fields
Cell line, Compound
View Samples- Homo sapiens
- 368 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Follicular lymphoma (FL) is genetically characterized by the presence of the t(14;18)(q32;q21) chromosomal translocation in approximately 90% of cases. In contrast to FL carrying the t(14;18), their t(14;18)-negative counterparts are less well studied regarding their immunohistochemical, genetic, molecular and clinical features. Within a previously published series of 184 FL grade 1-3A with available gene expression data, we identified 17 FL lacking the t(14;18). Comparative genomic hybridization and high resolution SNP array profiling demonstrated that gains/amplifications of the BCL2 gene locus in 18q were restricted to the t(14;18)-positive FL subgroup. A comparison of gene expression profiles revealed an enrichment of germinal center B-cell associated signatures in t(14;18)-positive FL, whereas activated B-cell like, NFB, proliferation and bystander cell signatures were enriched in t(14;18)-negative FL. These findings were confirmed by immunohistochemistry in an independent validation series of 84 FL, in which 32% of t(14;18)-negative FL showed weak or absent CD10 expression and 91% an increased Ki67 proliferation rate. Although overall survival did not differ between FL with and without t(14;18), our findings suggest distinct molecular features of t(14;18)-negative FL.
Publication Title
Follicular lymphomas with and without translocation t(14;18) differ in gene expression profiles and genetic alterations.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples