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GSE100617
Mus musculus, Homo sapiens
30 Downloadable Samples
Affymetrix Mouse Gene 2.1 ST Array (mogene21st), Affymetrix Mouse Gene 1.1 ST Array (mogene11st), Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
PML is a ROS sensor activating p53 upon oxidative stress.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Race, Time
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
The Pml gene is essential to the formation of PML nuclear bodies, domains which have been associated with various functions such as apoptosis/senescence, DNA repair and cell proliferation( Lallemand-Breitenbach 2010). PML-NBs formation is regulated by cellular stress including oxidative stress(Jeanne 2010, de The 2012). To investigate the role of PML in ROS response in vivo, we analyse the expression difference to the acetaminophen toxicity, which is initiated by ROS, in Pml wt and Pml KO mice.
Publication Title
PML is a ROS sensor activating p53 upon oxidative stress.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st), Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
The Pml gene is essential to the formation of PML nuclear bodies, domains which have been associated with various functions such as apoptosis/senescence, DNA repair and cell proliferation( Lallemand-Breitenbach 2010). PML-NBs formation is regulated by cellular stress including oxidative stress(Jeanne 2010, de The 2012). To investigate the role of PML in ROS response in vivo, we analyse the expression difference betweem Pml wt and Pml KO under fasted condition, which easily up-regulate ROS in BALB/cByJ background
Publication Title
PML is a ROS sensor activating p53 upon oxidative stress.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st), Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
PML nuclear bodies (NBs) recruit partner proteins -including p53 and its regulators- controlling their abundance or function. Investigating arsenic sensitivity of acute promyelocytic leukemia, we proposed that PML oxidation promotes NB-biogenesis. Yet, physiological links between PML and oxidative stress response in vivo remain unexplored. Here we identify PML as a reactive oxygen species (ROS) sensor. Pml-/- cells accumulate ROS, while PML expression decreases ROS levels. Unexpectedly, Pml-/- embryos survive acute glutathione depletion. Moreover, Pml-/- animals are resistant to acetaminophen hepatotoxicity or fasting-induced steatosis. Molecularly, Pml-/- animals fail to properly activate oxidative stress-responsive p53 targets, while NRF2 response is accelerated. Finally, in an oxidative stress-prone background, Pml-/- animals display a longevity phenotype, likely reflecting decreased basal p53 activation. Thus, similar to p53, PML exerts basal anti-oxidant properties, but also drives oxidative stress-induced changes in cell survival/proliferation or metabolism in vivo. Through NB-biogenesis, PML therefore couples ROS-sensing to p53 responses, shedding a new light on PML role in senescence or stem cell biology.
Publication Title
PML is a ROS sensor activating p53 upon oxidative stress.
Sample Metadata Fields
Sex, Cell line, Race, Time
View Samples- Homo sapiens
- 53 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: We have previously shown that the Gene expression Grade Index (GGI) was able to identify two subtypes of estrogen receptor (ER)-positive tumors that were associated with statistically distinct clinical outcomes in both untreated and tamoxifen-treated patients. Here, we aim to investigate the ability of the GGI to predict relapses in postmenopausal women who were treated with tamoxifen (T) or letrozole (L) within the BIG 1-98 trial.
Publication Title
The Gene expression Grade Index: a potential predictor of relapse for endocrine-treated breast cancer patients in the BIG 1-98 trial.
Sample Metadata Fields
Age, Specimen part, Disease stage, Treatment
View Samples- Homo sapiens
- 737 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Purpose: A number of microarray studies have reported distinct molecular profiles of breast cancers (BC): basal-like, ErbB2-like and two to three luminal-like subtypes. These were associated with different clinical outcomes. However, although the basal and the ErbB2 subtypes are repeatedly recognized, identification of estrogen receptor (ER)-positive subtypes has been inconsistent. Refinement of their molecular definition is therefore needed.
Publication Title
Definition of clinically distinct molecular subtypes in estrogen receptor-positive breast carcinomas through genomic grade.
Sample Metadata Fields
Age, Disease stage
View Samples- Mus musculus, Homo sapiens
- 4 Downloadable Samples
- Affymetrix HT MG-430 PM Array Plate (htmg430pm)
Description
Anamniotes, rodents and man maintain a pool of adult neural stem cells around the central canal in the spinal cord representing an attractive cellular source for endogenous repair. Cell diversity and genes specific for this niche are still ill-defined in mammals. To identify genes specifically expressed in the niche, we microdissected (with laser) the central canal region and the adjacent tissue in human and mice adult tissues. Total RNA was isolated and used to probe affymetrix microarrays
Publication Title
RNA Profiling of the Human and Mouse Spinal Cord Stem Cell Niches Reveals an Embryonic-like Regionalization with MSX1<sup>+</sup> Roof-Plate-Derived Cells.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 77 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: Estrogen receptor positive (ER+) breast cancers (BC) are heterogeneous with regard to their clinical behavior and response to therapies. The ER is currently the best predictor of response to the anti-estrogen agent tamoxifen, yet up to 30-40% of ER+BC will relapse despite tamoxifen treatment. New prognostic biomarkers and further biological understanding of tamoxifen resistance are required. We used gene expression profiling to develop an outcome-based predictor using a training set of 255 ER+ BC samples from women treated with adjuvant tamoxifen monotherapy. We used clusters of highly correlated genes to develop our predictor to facilitate both signature stability and biological interpretation. Independent validation was performed using 362 tamoxifen-treated ER+ BC samples obtained from multiple institutions and treated with tamoxifen only in the adjuvant and metastatic settings.
Publication Title
Predicting prognosis using molecular profiling in estrogen receptor-positive breast cancer treated with tamoxifen.
Sample Metadata Fields
Age, Disease stage, Treatment
View Samples- Homo sapiens
- 79 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Purpose: There is growing evidence that interaction between stromal and tumor cells is pivotal in breast cancer progression and response to therapy. Since the pioneer work of Allinen et al. suggested that during breast cancer progression striking changes occur in CD10+ stromal cells, we aimed to better characterize this cell population and its clinical relevance.
Publication Title
Characterization and clinical evaluation of CD10+ stroma cells in the breast cancer microenvironment.
Sample Metadata Fields
Specimen part, Disease stage
View Samples- Homo sapiens
- 197 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Background: Recently a 76-gene prognostic signature able to predict distant metastases in lymph node-negative (N-) breast cancer patients was reported. The aims of this study conducted by TRANSBIG were to independently validate these results and to compare the outcome with clinical risk assessment. Materials and Methods: Gene expression profiling of frozen samples from 198 N- systemically untreated patients was performed at the Bordet Institute, blinded to clinical data and independent of Veridex. Genomic risk was defined by Veridex, blinded to clinical data. Survival analyses, done by an independent statistician, were performed with the genomic risk and adjusted for the clinical risk, defined by Adjuvant!Online. Results: The actual 5- and 10-year time to distant metastasis (TDM) were 98% (88%-100%) and 94% (83%-98%) respectively for the good profile group and 76% (68%- 82%) and 73% (65%-79%) for the poor profile group. The actual 5- and 10-year overall survival (OS) were 98% (88%-100%) and 87% (73%-94%) respectively for the good profile group and 84% (77%-89%) and 72% (63%-78%) for the poor profile group. We observed a strong time-dependency of this signature, leading to an adjusted HR of 13.58 (1.85-99.63) and 8.20 (1.10-60.90) at 5 years, and 5.11 (1.57-16.67) and 2.55 (1.07-6.10) at 10 years for TDM and OS respectively. Conclusion: This independent validation confirmed the performance of the 76-gene signature and adds to the growing evidence that gene expression signatures are of clinical relevance, especially for identifying patients at high risk of early distant metastases.
Publication Title
Strong time dependence of the 76-gene prognostic signature for node-negative breast cancer patients in the TRANSBIG multicenter independent validation series.
Sample Metadata Fields
Age, Disease stage
View Samples