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Homo sapiens
13 Downloadable Samples
Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Bone is a frequent target of lung cancer metastasis, which is associated with significant morbidity and a dismal prognosis. To identify and functionally characterize genes involved in the mechanisms of osseous metastasis we developed a murine lung cancer model. Comparative transcriptomic analysis identified genes encoding signaling molecules (such as TCF4 and PRKD3), and cell anchorage related proteins (MCAM, and SUSD5), some of which were basally modulated by TGFbeta in tumor cells and in conditions mimicking tumor-stroma interactions. Triple gene combinations induced not only high osteoclastogenic activity but also a marked enhancement of global metalloproteolytic activities in vitro. These effects were strongly associated with robust bone colonization in vivo, whereas this gene subset was ineffective in promoting local tumor growth and cell homing activity to bone. Interestingly, global inhibition of metalloproteolytic activities and simultaneous TGFbeta blockade in vivo led to increased survival and a remarkable attenuation of bone tumor burden and osteolytic metastasis. Thus, this metastatic gene signature mediates bone-matrix degradation by a dual mechanism of induction of TGFbeta-dependent osteoclastogenic bone resorption and enhancement of stroma-dependent metalloproteolytic activities. Our findings suggest the cooperative contribution of host-derived and cell-autonomous effects directed by a small subset of genes in mediating aggressive osseous colonization.
Publication Title
A novel lung cancer signature mediates metastatic bone colonization by a dual mechanism.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Interactions between the gene products encoded by the mitochondrial and nuclear genomes play critical roles in normal eukaryotic cellular function. Here, we characterized the metabolic and transcriptional properties of A549 lung cancer cells and their isogenic mitochondrial DNA (mtDNA)-depleted rho zero counterparts grown in cell culture and as tumor xenografts in immune-deficient mice. A manuscript summarizing our conclusions is under review.
Publication Title
mtDNA depletion confers specific gene expression profiles in human cells grown in culture and in xenograft.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 24 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Synthesis and anticancer properties of water-soluble zinc ionophores.
Sample Metadata Fields
No sample metadata fields
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GSE2189- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Human lung cancer (A549) cells were treated 50uM of the metal cation-containing chemotherapeutic drug motexafin gadolinium (MGd) for 4, 12, and 24 hrs and expression compared to control cells (treated with 5% mannitol for the same length of time)
Publication Title
Motexafin gadolinium disrupts zinc metabolism in human cancer cell lines.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We have demonstrated that water-soluble zinc ionophores can be administered to mice at relatively high doses and inhibit the growth of A549 lung cancer cells grown in xenograft models. Gene expression profiles of tumor specimens harvested from mice four hours after treatment confirmed that the activation of stress responsive genes occurs in vivo. These findings lead us to propose that the pharmacologic delivery of zinc to tumors using water solubilized ionophores is a potential approach to cancer therapy.
Publication Title
Synthesis and anticancer properties of water-soluble zinc ionophores.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We have shown that water solubilized versions of a zinc ionophore increase intracellular concentrations of free zinc and have antiproliferative activity in exponential phase A549 lung cancer cultures. The gene expression profiles of A549 lung cancer cultures treated with the lead compound PCI-5002 reveal the activation of stress response pathways. Medium supplementation with zinc (25 M) led to activation of additional oxidative stress response as well as apoptotic pathways. We propose that the pharmacologic delivery of zinc to tumors using water solubilized ionophores is a potential approach to cancer therapy.
Publication Title
Synthesis and anticancer properties of water-soluble zinc ionophores.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The goal of this project was to characterize changes in gene expression in response to the anti-cancer agent sapphyrin PCI-2050. Cultured A549 human lung cancer cells were treated with sapphyrin PCI-2050 or actinomycin D, a known transcripitonal inhibitor. The gene expression profiles of drug-treated and control A549 cultures were determined using Human Genome U133 Plus 2.0 Arrays (Affymetrix, Santa Clara, CA). Further details are provided in our published manuscript: <http://www.molecular-cancer.com/content/6/1/9>.
Publication Title
Synthesis and biologic properties of hydrophilic sapphyrins, a new class of tumor-selective inhibitors of gene expression.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Pancreatic Ductal Adenocarcinoma (PDA) is a critical health issue in cancer field with little new therapeutic options. Several evidences support an implication of intra-tumoral microenvironment (stroma) on PDA progression. However, its contribution to the role of neuroplastic changes within pathophysiology and clinical course of PDA, mainly through tumor recurrence and neuropathic pain, remains unknown neglecting a putative therapeutic window. Here, we report that intra-tumoral microenvironment is a mediator of PDA Associated Neural Remodeling (PANR). With laser capture microdissection of stromal/tumoral compartment from human PDA followed by cDNA based microarray analyses we highlighted numerous factors expressed by stromal compartment that could impact on neuroplastic changes; among them, the Slit2/Robo axon guidance pathway. Using co-culture in vitro, we showed that stromal secreted Slit2 increases DRG neurite outgrowth and Schwann cells migration/proliferation by modulating N-Cadherin/-Catenin signaling. Importantly, Slit2/Robo signaling inhibition disrupts this stromal/neural connection. Finally, we revealed in vivo that Slit2 expression is correlated with neural remodeling within Human and mouse PDA. These results demonstrate the implication of microenvironment, through secretion of axon guidance molecule, in PANR. Furthermore, it provides rationale to investigate the disruption of stromal/neural compartment dialogue by using Slit2/Robo pathway inhibitors for treatment of pancreatic cancer recurrence and associated pain.
Publication Title
Stromal SLIT2 impacts on pancreatic cancer-associated neural remodeling.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 35 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Disruption of N-linked glycosylation has a broad impact on proper glycosylation of nascent glycoproteins in the endoplasmic reticulum, which affect multiple signalling pathways( by changing the stability of membrane proteins or the signalling ability of membrane receptors) and may be responsible of the fibrotic stage associated to CDG type-I.
Publication Title
Fibrotic response in fibroblasts from congenital disorders of glycosylation.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 26 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
This work uses a time series in order to decipher gene relationships and consequently to build core regulatory networks involved in Arabidopsis root adaptation to NO3- provision. The experimental approach has been to monitor genome response to NO3- at 3, 6, 9, 12, 15 and 20 min, using ATH1 chips. This high-resolution time course analysis demonstrated that the previously known primary nitrate response is actually preceded by very fast (within 3 min) gene expression modulation, involving genes/functions needed to prepare plants to use/reduce NO3-. State-space modeling (a machine learning approach) has been used to successfully predict gene behavior in unlearnt conditions.
Publication Title
Predictive network modeling of the high-resolution dynamic plant transcriptome in response to nitrate.
Sample Metadata Fields
Specimen part, Treatment
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