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Homo sapiens
20 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Chemotherapy resistance presents a major hurdle for cancer treatment. We proposed to identify the molecular changes through which breast cancer cells evolve resistance to conventional treatment, here cisplatin, so targeted therapy can be developed. Candidate approach RNAi screening was combined with cisplatin treatment in order to identify molecular pathways conferring survival advantages. The screening identified ATP7A, a copper transport ATPase responsible for the intercellular movement and sequestering of cisplatin, as a therapeutic target. Copper chelation with tetrathiomolybdate (TM) targets ATP7A. TM in combination with cisplatin sensitized drug-resistant breast cancer cells. Allograft and xenograft models in aythymic mice treated with TM/cisplatin combination therapy inhibited tumor growth and increased survival compared with monotreated mice. Examination of the molecular effects of TM on cisplatin efficacy in drug-resistant tumors revealed reduced levels of APT7A, reduced cisplatin sequestering by ATP7A and increased nuclear availability of cisplatin. Further, we showed that TM treatment combined with cisplatin reduced the half-life of ATP7A in human breast cancer cell lines. This finding offered the potential to combat drug platinum-resistant tumors and sensitize patients to conventional breast cancer treatments by identifying and targeting resistant tumors unique molecular adaptations.
Publication Title
Ammonium tetrathiomolybdate treatment targets the copper transporter ATP7A and enhances sensitivity of breast cancer to cisplatin.
Sample Metadata Fields
Cell line, Time
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Cancer metastasis is a fetal problem that claims life of over 90% of cancer patients. It is hypothesized that cancer stem cells (CSCs) mediate cancer metastasis and such cells are often resistant to chemotherapy. Studying BRCA1 associated cancers, we found that CSCs form fillopodia and protrusions enriching for active forms of ezrin/radixin/moesin proteins and they have a much higher potential to metastasize than non-CSCs. Microarray analysis indicated that many pathways related to cell adhesion, extracellular matrix and cytoskeleton were differentially regulated in CSCs. Although inhibition of cytoskeleton remodeling by cisplatin treatment retarded CSC motility and cancer metastasis, drug resistant cancers eventually emerge containing markedly increased number of CSCs. This event is at least partially attributed to the activation of PI3K/mTOR signaling, and can be significantly inhibited by the treatment of rapamycin. These results provide strong evidence that cytoskeletal rearrangement and PI3K/mTOR signaling play a distinct role in mediating CSC mobility and viability, and blocking of both pathways in CSCs synergistically inhibits primary and metastatic cancer growth in BRCA1 associated tumors.
Publication Title
Synergistic therapeutic effect of cisplatin and phosphatidylinositol 3-kinase (PI3K) inhibitors in cancer growth and metastasis of Brca1 mutant tumors.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 27 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
While adipogenesis is controlled by a cascade of transcription factors, the global gene expression profiles in the early phase of adipogenesis are not well defined. Using microarray analysis of gene expression in 3T3-L1 cells we have identified evidence for the activity of 2568 genes during the early phase of adipocyte differentiation. One of these, ISL1, was of interest since its expression was markedly upregulated at 1 h after initiation of differentiation with a subsequent rapid decline. Overexpression of ISL1 at early times during adipocyte differentiation, but not at later times, was found to profoundly inhibit differentiation. This was accompanied by moderate down-regulation of PPARg levels, substantial down-regulation of PPARg downstream genes and down-regulation of BMP4 levels in preadipocytes. Readdition of BMP4 overcame the inhibitory effect of ISL1 on PPARg but not aP2 expression, a downstream gene of PPARg; and BMP4 also partially rescued ISL1 inhibition of adipogenesis, an effect which is additive with rosiglitazone. These results suggest that ISL1 is intimately involved in early regulation of adipogenesis, modulating PPARg expression and activity via BMP4-dependent and -independent mechanisms. Our time course gene expression survey sets the stage for further studies to explore other early and immediate regulators.
Publication Title
ISL1 regulates peroxisome proliferator-activated receptor γ activation and early adipogenesis via bone morphogenetic protein 4-dependent and -independent mechanisms.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
The highly aggressive muscle cancer alveolar rhabdomyosarcoma (ARMS) is one of the most common soft tissue sarcoma of childhood, yet the outcome for unresectable and metastatic disease is dismal and unchanged for nearly 3 decades. To better understand the pathogenesis of this disease and to facilitate novel preclinical approaches, we previously developed a conditional mouse model of ARMS by faithfully recapitulating the genetic mutations observed in the human disease, i.e. activation of Pax3:Fkhr fusion gene with either p53 or Cdkn2a inactivation. In this report we show that this model recapitulates the immunohistochemical profile and the rapid progression of the human disease. We demonstrate that Pax3:Fkhr expression increases during late preneoplasia, but that tumor cells undergoing metastasis are under apparent selection for Pax3:Fkhr expression. At a whole genome level, a cross-species gene set enrichment analysis and metagene projection study showed that our mouse model is most similar to human ARMS when compared to other pediatric cancers. We have defined an expression profile conserved between mouse and human ARMS as well as a Pax3:Fkhr signature, including the target gene, SKP2. We further identified 7 druggable kinases over-expressed across species. The data affirms the accuracy of this genetically engineered mouse model.
Publication Title
Credentialing a preclinical mouse model of alveolar rhabdomyosarcoma.
Sample Metadata Fields
Disease, Disease stage
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Pompe disease is caused by autosomal recessive mutations in the GAA gene, which encodes acid alpha-glucosidase. Although enzyme replacement therapy has recently improved patient survival greatly, the results in skeletal muscles and for advanced disease are still not satisfactory. Here, we report the derivation of Pompe disease induced pluripotent stem cells (PomD-iPSCs) and their potential for pathogenesis modeling, drug testing and disease marker identification. PomD-iPSCs maintained pluripotent features, and had low GAA activity and high glycogen content. Cardiomyocyte-like cells (CMLCs) differentiated from PomD-iPSCs recapitulated the hallmark Pompe disease pathophysiological phenotypes, including high levels of glycogen, abundant intracellular LAMP-1- or LC3-positive granules, and multiple ultrastructural aberrances. Drug rescue assessment showed that exposure of PomD-iPSC-derived CMLCs to rhGAA reversed the major pathologic phenotypes. Further, L-carnitine and 3- methyladenine treatment reduced defective cellular respiration and buildup of phagolysosomes, respectively, in the diseased cells. By comparative transcriptome analysis, we identified glycogen metabolism, lysosome and mitochondria related marker genes whose expression robustly correlated with the therapeutic effect of drug treatment in PomD-iPSC-derived CMLCs. Collectively, these results demonstrate that PomD-iPSCs are a promising in vitro disease model for development of novel therapeutic strategies for Pompe disease.
Publication Title
Human Pompe disease-induced pluripotent stem cells for pathogenesis modeling, drug testing and disease marker identification.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Aim: To generate human embryonic stem cell-derived corneal endothelial cells (hESC-CECs) for transplantation in patients with corneal endothelial dystrophies.
Publication Title
Efficient Generation of Human Embryonic Stem Cell-Derived Corneal Endothelial Cells by Directed Differentiation.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 74 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Mounting evidence points to a link between a cancer possessing stem-like properties and a worse prognosis. To understand the biology, a common approach is to integrate network biology with signal processing mechanics. That said, even with the right tools, predicting the risk for a highly susceptible target using only a handful of gene signatures remains very difficult. By compiling the expression profiles of a panel of tumor stem-like cells (TSLCs) originating in different tissues, comparing these to their parental tumor cells (PTCs) and the human embryonic stem cells (hESCs), and integrating network analysis with signaling mechanics, we propose that network topologically-weighted signaling processing measurements under tissue-specific conditions can provide scalable and predicable target identification.
Publication Title
Network biology of tumor stem-like cells identified a regulatory role of CBX5 in lung cancer.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Retinal ganglion cells (RGCs) and retinal pigment epithelium (RPE) cells are two retinal cell types that are affected by the most prevalent retinal diseases leading to irreversible blindness, such as glaucoma affecting the former and age-related macular degeneration affecting the latter. One of the most promising approaches for the therapy of these diseases is via the autologous transplantation of RGC or RPE cells derived from the induced pluripotent stem cells (iPSCs). This emphasizes the importance of detailed characterization and understanding of the mechanisms of differentiation of iPSCs into retinal lineages on the genome-wide scale. Such information can be used to identify novel crucial regulators of differentiation, optimisation of differentiation protocols to make them more efficient and safe, identification of novel specific biomarker signatures of differentiated cells. In this study, we performed the genome-wide transcriptome analysis of terminally differentiated RGC and RPE lineages, as well as intermediate retinal progenitor cells (RPCs) of optic vesicles (OVs) derived from the human induced pluripotent stem cells (iPSCs). In our analysis we specifically focused on the classes of transcripts that encode regulators of gene expression, such as transcription factors, epigenetic factors, and components of signaling pathways.
Publication Title
Expression profiling of cell-intrinsic regulators in the process of differentiation of human iPSCs into retinal lineages.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Compared the global gene expression profiles of HD- and CON-iPSC-derived neurons
Publication Title
Elucidating the role of the A2A adenosine receptor in neurodegeneration using neurons derived from Huntington's disease iPSCs.
Sample Metadata Fields
Sex, Age, Specimen part
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GSE13727- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis
Publication Title
Granulysin is a key mediator for disseminated keratinocyte death in Stevens-Johnson syndrome and toxic epidermal necrolysis.
Sample Metadata Fields
No sample metadata fields
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