Filters
Technology
Platform
SRP047251
Homo sapiens
9 Downloadable Samples
IonTorrentProton
Description
Phosphoinositide-3-kinase (PI3K)-a inhibitors are clinically active in squamous carcinoma (SCC) of the head and neck (H&N) bearing mutations or amplification of PIK3CA. We aimed to identify potential mechanism of resistance and have observed that SCCs cells overcome the antitumor effects of the PI3Ka inhibitor BYL719 by maintaining PI3K-independent activation of the mammalian target of rapamycin (mTOR). The persistent mTOR activation is mediated by the tyrosine kinase receptor AXL. We found that AXL is overexpressed in resistant tumors, dimerizes with the epidermal growth factor receptor (EGFR), phosphorylates EGFR tyrosine 1173, resulting in activation of phospholipase C? (PLC?)- protein kinase C (PKC) that, in turn, activates mTOR. Finally, simultaneous treatment with PI3Ka and either EGFR, AXL or PKC inhibitors reverts this resistance. Overall design: RNAseq from acquired resistant cells CAL33B, K180B were compared to their parental counterpart CAL33 and K180, respectively. K180 is a shortcut of KYSE180, and B stands for BYL719. Duplicate of parental sensitive cells and K180B, and triplicate for CAL33B.
Publication Title
AXL mediates resistance to PI3Kα inhibition by activating the EGFR/PKC/mTOR axis in head and neck and esophageal squamous cell carcinomas.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
Affymetrix HT Human Genome U133A Array (hthgu133a)
Description
To investigate the oxidant sensitivity of E/ER regulated gene expression, E/ER regulated genes are identified using E deprivation or
Publication Title
Genes responsive to both oxidant stress and loss of estrogen receptor function identify a poor prognosis group of estrogen receptor positive primary breast cancers.
Sample Metadata Fields
No sample metadata fields
View Samples- Caenorhabditis elegans
- 51 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
DAF-16/FOXO and EGL-27/GATA promote developmental growth in response to persistent somatic DNA damage.
Sample Metadata Fields
Treatment
View Samples- Caenorhabditis elegans
- 36 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
Genome maintenance defects cause complex disease phenotypes characterized by developmental failure, cancer susceptibility and premature aging. It remains poorly understood how DNA damage responses function during organismal development and maintain tissue functionality when DNA damage accumulates with aging. Here we show that the FoxO transcription factor DAF-16 is activated in response to DNA damage during development while the DNA damage responsiveness of DAF-16 declines with aging. We find that in contrast to its established role in mediating starvation arrest, DAF-16 alleviates DNA damage induced developmental arrest and even in the absence of DNA repair promotes developmental growth and enhances somatic tissue functionality. We demonstrate that the GATA transcription factor EGL-27 co-regulates DAF-16 target genes in response to DNA damage and together with DAF-16 promotes developmental growth. We propose that EGL-27/GATA activity specifies DAF-16 mediated DNA damage responses to enable developmental progression and to prolong tissue functioning when DNA damage persists.
Publication Title
DAF-16/FOXO and EGL-27/GATA promote developmental growth in response to persistent somatic DNA damage.
Sample Metadata Fields
Treatment
View Samples- Caenorhabditis elegans
- 15 Downloadable Samples
Affymetrix C. elegans Genome Array (celegans)
Description
Genome maintenance defects cause complex disease phenotypes characterized by developmental failure, cancer susceptibility and premature aging. It remains poorly understood how DNA damage responses function during organismal development and maintain tissue functionality when DNA damage accumulates with aging. Here we show that the FoxO transcription factor DAF-16 is activated in response to DNA damage during development while the DNA damage responsiveness of DAF-16 declines with aging. We find that in contrast to its established role in mediating starvation arrest, DAF-16 alleviates DNA damage induced developmental arrest and even in the absence of DNA repair promotes developmental growth and enhances somatic tissue functionality. We demonstrate that the GATA transcription factor EGL-27 co-regulates DAF-16 target genes in response to DNA damage and together with DAF-16 promotes developmental growth. We propose that EGL-27/GATA activity specifies DAF-16 mediated DNA damage responses to enable developmental progression and to prolong tissue functioning when DNA damage persists.
Publication Title
DAF-16/FOXO and EGL-27/GATA promote developmental growth in response to persistent somatic DNA damage.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The tumorigenicity of human pluripotent stem cells (hPSCs) is a major safety concern for their application in regenerative medicine. Here we identify the tight-junction protein Claudin-6 as a specific cell surface marker of hPSCs that can be used to selectively remove Claudin-6-positive cells from mixed cultures. We show that Claudin-6 is absent in adult tissues but highly expressed in undifferentiated cells, where it is dispensable for hPSC survival and self-renewal. We use three different strategies to remove Claudin-6-positive cells from mixed populations: an antibody against Claudin-6; a cytotoxin-conjugated antibody that selectively targets undifferentiated cells; and clostridium perfringens enterotoxin, a toxin that binds several Claudins, including Claudin-6, and efficiently kills undifferentiated cells, thus eliminating the tumorigenic potential of hPSC-containing cultures. This work provides a proof of concept for the use of Claudin-6 to eliminate residual undifferentiated hPSCs from culture, highlighting a strategy that may increase the safety of hPSC-based cell therapies.
Publication Title
Immunologic and chemical targeting of the tight-junction protein Claudin-6 eliminates tumorigenic human pluripotent stem cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Pluripotent-specific inhibitors (PluriSIns) make a powerful tool for studying the mechanisms that control the survival of human pluripotent stem cells (hPSCs). Here we characterize PluriSIn#2 as a novel selective indirect inhibitor of topoisomerase II alpha (TOP2A). We find that TOP2A is uniquely expressed in undifferentiated hPSCs, and that its inhibition results in their rapid cell death. These findings reveal a dependency of hPSCs on the activity of TOP2A, which can be harnessed for their selective elimination from culture.
Publication Title
Brief reports: Controlling the survival of human pluripotent stem cells by small molecule-based targeting of topoisomerase II alpha.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Caenorhabditis elegans
- 12 Downloadable Samples
- Affymetrix C. elegans Gene 1.0 ST Array (elegene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Toxicogenomics of iron oxide nanoparticles in the nematode C. elegans.
Sample Metadata Fields
Specimen part
View Samples- Caenorhabditis elegans
- 6 Downloadable Samples
- Affymetrix C. elegans Gene 1.0 ST Array (elegene10st)
Description
Superparamagnetic Iron Oxide Nanoparticles (SPIONs) are currently being investigated for a range of biomedical applications. Their use have been related with different cytotoxic mechanisms including the generation of oxidative stress and the induction of metal detoxification pathways, among others. We have investigated the molecular mechanisms responsive to in-house fabricated citrate coated SPIONs (C-SPIONs) in the nematode C. elegans to compare in vivo findings with previous in vitro studies. C-SPIONs (500 g/ml) affected the transcriptional response of signal transduction cascades (i.e. TFG-beta), protein processing in the endoplasmic reticulum, and RNA transport, among other biological processes. They also triggered a lysosomal response, indicating a relevant biological role of this cellular compartment in the response to this nanoparticle treatment in C. elegans. Interestingly, other pathways frequently linked to nanotoxicity like oxidative stress or apoptosis were not identified as significantly affected in this genome-wide in vivo study despite the high dose of exposure.
Publication Title
Toxicogenomics of iron oxide nanoparticles in the nematode C. elegans.
Sample Metadata Fields
Specimen part
View Samples- Caenorhabditis elegans
- 6 Downloadable Samples
- Affymetrix C. elegans Gene 1.0 ST Array (elegene10st)
Description
Superparamagnetic Iron Oxide Nanoparticles (SPIONs) are currently being investigated for a range of biomedical applications. Their use have been related with different cytotoxic mechanisms including the generation of oxidative stress and the induction of metal detoxification pathways, among others. Different NP coatings are being explored, among them albumin which has been applied in some drugs delivery systems. We have investigated the molecular mechanisms responsive to in-house fabricated SPIONs coated with bovine serum albumin (BSA-SPIONs) in the nematode C. elegans to compare in vivo findings with previous in vitro studies. BSA-SPIONs (500 g/ml) affected the transcriptional response of glycan metabolic pathways related to innate immune response, xenobiotics degradation, and triggered a lysosomal response, indicating a relevant biological role of this cellular compartment in the response to this nanoparticle treatment in C. elegans. Remarkably, key biological functions such as apoptosis or protein processing were not affected with significance despite the high dose of exposure.
Publication Title
Toxicogenomics of iron oxide nanoparticles in the nematode C. elegans.
Sample Metadata Fields
Specimen part
View Samples