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GSE53514
Homo sapiens
34 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
CD4(+) type 1 T regulatory (Tr1) cells are induced in the periphery and have a pivotal role in promoting and maintaining tolerance. The absence of surface markers that uniquely identify Tr1 cells has limited their study and clinical applications. By gene expression profiling of human Tr1 cell clones, we identified the surface markers CD49b and lymphocyte activation gene 3 (LAG-3) as being stably and selectively coexpressed on mouse and human Tr1 cells. We showed the specificity of these markers in mouse models of intestinal inflammation and helminth infection and in the peripheral blood of healthy volunteers. The coexpression of CD49b and LAG-3 enables the isolation of highly suppressive human Tr1 cells from in vitro anergized cultures and allows the tracking of Tr1 cells in the peripheral blood of subjects who developed tolerance after allogeneic hematopoietic stem cell transplantation. The use of these markers makes it feasible to track Tr1 cells in vivo and purify Tr1 cells for cell therapy to induce or restore tolerance in subjects with immune-mediated diseases.
Publication Title
Coexpression of CD49b and LAG-3 identifies human and mouse T regulatory type 1 cells.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
Three HL cell lines (HD-MyZ, L-540 and HDLM-2) were used to investigate the effects of perifosine and sorafenib using in vitro assays analyzing cell growth, cell cycle distribution, gene expression profiling (GEP), and apoptosis. Western blotting (WB) experiments were performed to determine whether the two-drug combination affected MAPK and PI3K/AKT pathways as well as apoptosis. Additionally, the antitumor efficacy and mechanism of action of perifosine/sorafenib combination were investigated in vivo in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice using tumor growth rates and survival as endpoints. RESULTS: While perifosine and sorafenib as single agents exerted a limited activity against HL cells, exposure of HD-MyZ and L-540 cell lines, but not HDLM-2 cells, to perifosine/sorafenib combination resulted in synergistic cell growth inhibition (40% to 80%) and cell cycle arrest. Upon perifosine/sorafenib exposure, L-540 cell line showed significant levels of apoptosis (up to 70%, P .0001) associated with severe mitochondrial dysfunction (cytochrome c, apoptosis-inducing factor release and marked conformational change of Bax accompanied by membrane translocation). Apoptosis induced by perifosine/sorafenib combination did not result in processing of caspase-8, -9, -3, or cleavage of PARP, and was not reversed by the pan-caspase inhibitor Z-VADfmk, supporting a caspase-independent mechanism of cell death. In responsive cell lines, WB analysis showed that antiproliferative and pro-apototic events were associated with dephosphorylation of MAPK and PI3K/Akt pathways. GEP analysis of HD-MyZ and L-540 cell lines, but not HDLM-2 cells indicated that perifosine/sorafenib treatment induced upregulation of genes involved in amino acid metabolism and downregulation of genes regulating cell cycle, DNA replication and cell death. In addition, in responsive cell lines, perifosine/sorafenib combination strikingly induced the expression of tribbles homologues 3 (TRIB3) both in vitro and in vivo. Silencing of TRIB3 prevented cell growth reduction induced by perifosine/sorafenib treatment. In vivo, the combined perifosine/sorafenib treatment significantly increased the median survival of NOD/SCID mice xenografted with HD-MyZ cell line as compared to controls (81 vs 45 days, P .0001) as well as mice receiving perifosine alone (49 days, P .03) or sorafenib alone (54 days, P .007). In mice bearing subcutaneous nodules generated by HD-MyZ and L-540 cell lines but not HDLM-2 cell line, perifosine/sorafenib treatment induced significantly increased levels of apoptosis (2- to 2.5-fold, P .0001) and necrosis (2- to 8-fold, P .0001), as compared to controls or treatment with single agents. In addition, perifosine/sorafenib treatment had no effect on HDLM-2 nodules, but significantly reduced L-540 nodules with 50% tumor growth inhibition, compared to controls. CONCLUSIONS: Perifosine/sorafenib combination resulted in strong anti-HL activity both in vitro and in vivo. These results warrant clinical evaluation of perifosine/sorafenib combined-treatment in HL patients.
Publication Title
Perifosine and sorafenib combination induces mitochondrial cell death and antitumor effects in NOD/SCID mice with Hodgkin lymphoma cell line xenografts.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
Three HL cell lines (HD-MyZ, L-540 and HDLM-2) were used to investigate the effects of perifosine and sorafenib using in vitro assays analyzing cell growth, cell cycle distribution, gene expression profiling (GEP), and apoptosis. Western blotting (WB) experiments were performed to determine whether the two-drug combination affected MAPK and PI3K/AKT pathways as well as apoptosis. Additionally, the antitumor efficacy and mechanism of action of perifosine/sorafenib combination were investigated in vivo in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice using tumor growth rates and survival as endpoints. RESULTS: While perifosine and sorafenib as single agents exerted a limited activity against HL cells, exposure of HD-MyZ and L-540 cell lines, but not HDLM-2 cells, to perifosine/sorafenib combination resulted in synergistic cell growth inhibition (40% to 80%) and cell cycle arrest. Upon perifosine/sorafenib exposure, L-540 cell line showed significant levels of apoptosis (up to 70%, P .0001) associated with severe mitochondrial dysfunction (cytochrome c, apoptosis-inducing factor release and marked conformational change of Bax accompanied by membrane translocation). Apoptosis induced by perifosine/sorafenib combination did not result in processing of caspase-8, -9, -3, or cleavage of PARP, and was not reversed by the pan-caspase inhibitor Z-VADfmk, supporting a caspase-independent mechanism of cell death. In responsive cell lines, WB analysis showed that antiproliferative and pro-apototic events were associated with dephosphorylation of MAPK and PI3K/Akt pathways. GEP analysis of HD-MyZ and L-540 cell lines, but not HDLM-2 cells indicated that perifosine/sorafenib treatment induced upregulation of genes involved in amino acid metabolism and downregulation of genes regulating cell cycle, DNA replication and cell death. In addition, in responsive cell lines, perifosine/sorafenib combination strikingly induced the expression of tribbles homologues 3 (TRIB3) both in vitro and in vivo. Silencing of TRIB3 prevented cell growth reduction induced by perifosine/sorafenib treatment. In vivo, the combined perifosine/sorafenib treatment significantly increased the median survival of NOD/SCID mice xenografted with HD-MyZ cell line as compared to controls (81 vs 45 days, P .0001) as well as mice receiving perifosine alone (49 days, P .03) or sorafenib alone (54 days, P .007). In mice bearing subcutaneous nodules generated by HD-MyZ and L-540 cell lines but not HDLM-2 cell line, perifosine/sorafenib treatment induced significantly increased levels of apoptosis (2- to 2.5-fold, P .0001) and necrosis (2- to 8-fold, P .0001), as compared to controls or treatment with single agents. In addition, perifosine/sorafenib treatment had no effect on HDLM-2 nodules, but significantly reduced L-540 nodules with 50% tumor growth inhibition, compared to controls. CONCLUSIONS: Perifosine/sorafenib combination resulted in strong anti-HL activity both in vitro and in vivo. These results warrant clinical evaluation of perifosine/sorafenib combined-treatment in HL patients.
Publication Title
Perifosine and sorafenib combination induces mitochondrial cell death and antitumor effects in NOD/SCID mice with Hodgkin lymphoma cell line xenografts.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
Three HL cell lines (HD-MyZ, L-540 and HDLM-2) were used to investigate the effects of perifosine and sorafenib using in vitro assays analyzing cell growth, cell cycle distribution, gene expression profiling (GEP), and apoptosis. Western blotting (WB) experiments were performed to determine whether the two-drug combination affected MAPK and PI3K/AKT pathways as well as apoptosis. Additionally, the antitumor efficacy and mechanism of action of perifosine/sorafenib combination were investigated in vivo in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. While perifosine and sorafenib as single agents exerted a limited activity against HL cells, exposure of HD-MyZ and L-540 cell lines, but not HDLM-2 cells, to perifosine/sorafenib combination resulted in synergistic cell growth inhibition (40% to 80%) and cell cycle arrest. Upon perifosine/sorafenib exposure, L-540 cell line showed significant levels of apoptosis (up to 70%, P .0001) associated with severe mitochondrial dysfunction (cytochrome c, apoptosis-inducing factor release and marked conformational change of Bax accompanied by membrane translocation). Apoptosis induced by perifosine/sorafenib combination did not result in processing of caspase-8, -9, -3, or cleavage of PARP, and was not reversed by the pan-caspase inhibitor Z-VADfmk, supporting a caspase-independent mechanism of cell death. In responsive cell lines, WB analysis showed that antiproliferative and pro-apototic events were associated with dephosphorylation of MAPK and PI3K/Akt pathways. GEP analysis of HD-MyZ and L-540 cell lines, but not HDLM-2 cells indicated that perifosine/sorafenib treatment induced upregulation of genes involved in amino acid metabolism and downregulation of genes regulating cell cycle, DNA replication and cell death. In addition, in responsive cell lines, perifosine/sorafenib combination strikingly induced the expression of tribbles homologues 3 (TRIB3) both in vitro and in vivo. Silencing of TRIB3 prevented cell growth reduction induced by perifosine/sorafenib treatment. In vivo, the combined perifosine/sorafenib treatment significantly increased the median survival of NOD/SCID mice xenografted with HD-MyZ cell line as compared to controls (81 vs 45 days, P .0001) as well as mice receiving perifosine alone (49 days, P .03) or sorafenib alone (54 days, P .007). In mice bearing subcutaneous nodules generated by HD-MyZ and L-540 cell lines but not HDLM-2 cell line, perifosine/sorafenib treatment induced significantly increased levels of apoptosis (2- to 2.5-fold, P .0001) and necrosis (2- to 8-fold, P .0001), as compared to controls or treatment with single agents. Perifosine/sorafenib combination resulted in strong anti-HL activity both in vitro and in vivo. These results warrant clinical evaluation of perifosine/sorafenib combined-treatment in HL patients.
Publication Title
Perifosine and sorafenib combination induces mitochondrial cell death and antitumor effects in NOD/SCID mice with Hodgkin lymphoma cell line xenografts.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Junction Adhesion Molecule-A (JAM-A) is present on leukocytes and platelets where it promotes cell adhesion and motility. We are interested in an interaction between JAM-A and tumor progression/metastases. To address this point, we mated JAM-A-/- mice and mouse mammary tumor model MMTV-PyMT mice which, which express polyoma middle T antigen under the control of mouse mammary tumor virus. MMTV-PyMT mice show 100% penetration of mammary tumor and highly metastases to lung. MMTV-PyMT mice without JAM-A show less primary tumor progression, therefore JAM-A enhance primary tumor progression. Then we are addressing the molecular mechanism of this phenomenon by in vivo. Furthermore, we would like to examine JAM-A deficient MMTV tumor signature.
Publication Title
Abrogation of junctional adhesion molecule-A expression induces cell apoptosis and reduces breast cancer progression.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Demethyl fructiculin A is a diterpenoid quinone component of the exudates from Salvia corrugata (SCO-1) leafes. SCO-1 was recently reported to induce anoikis in mammalian cell lines via a molecular mechanism involving the presence of the membrane scavenging receptor CD36. However, experiments performed with cells lacking CD36, showed that SCO-1 was able to induce apoptosis also via alternate pathways. To contribute to a better characterization of the molecular mechanisms underlining the cytotoxic activity of SCO-1, we decided to pursue an unbiased pharmacogenomic approach by generating the gene expression profile of GBM TICs subjected to the administration of SCO-1 and comparing it with that of control cells exposed to the solvent. With this strategy we hypothesized to highlight those pathways and biological processes unlashed by SCO-1.
Publication Title
Demethyl fruticulin A (SCO-1) causes apoptosis by inducing reactive oxygen species in mitochondria.
Sample Metadata Fields
Time
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Neural stem cells from different brain regions show differencies in gene expression patterns and physiological functions.
Publication Title
Innate neural stem cell heterogeneity determines the patterning of glioma formation in children.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Helicobacter pylori clinical isolates can establish themselves in gastric epithelial stem cells and this interaction may have implications for gastric tumorigenesis. Mouse gastric epithelial progenitor cells (mGEPs) and non-progenitor gastric epithelial cells (npGECs) were infected for 24hrs with Helicobacter pylori clinical isolates Kx1 and Kx2. Kx1 was isolated from a patient with chronic atrophic gastritis (ChAG) and Kx2 from the same patient 4 years later, when he progressed to gastric adenocarcinoma.
Publication Title
Helicobacter pylori evolution during progression from chronic atrophic gastritis to gastric cancer and its impact on gastric stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We generated the transcriptional regulatory footprint of phthalimide neovascular factor 1 (PNF1)a novel synthetic small molecule that exhibits significant in vitro endothelial potency and significant in vivo microvascular network expansionby performing comparative microarray analysis on PNF1-stimulated (versus control) human microvascular endothelial cells (HMVEC) spanning 1-48 h post-supplementation. We subsequently applied network analysis tools (including substantial libraries of information regarding known associations among network components) to elucidate key signaling components and pathways involved in the PNF1 mechanism-of-action. We identified that PNF1 first induces function of the tumor necrosis factor-alpha (TNF-) signaling pathway, which in turn affects transforming growth factor-beta (TGF-) signaling.
Publication Title
Mechanistic exploration of phthalimide neovascular factor 1 using network analysis tools.
Sample Metadata Fields
Cell line
View Samples- Caenorhabditis elegans
- 12 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
Analysis of gene expression in worms exposed to PA14 for 4 hours. Worms used were wild-type or fshr-1(ok778) mutants. Comparisons allowed determination of fshr-1-dependent gene expression.
Publication Title
The Conserved G-Protein Coupled Receptor FSHR-1 Regulates Protective Host Responses to Infection and Oxidative Stress.
Sample Metadata Fields
No sample metadata fields
View Samples