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Homo sapiens
35 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Soft tissue sarcomas are a diverse set of fatal human tumors where few agents have demonstrable clinical efficacy, with the standard therapeutic combination of doxorubicin and ifosfamide showing only a 25-30% response rate in large multi-institutional trials. Although liposarcomas are the most common histological form of adult soft tissue sarcomas, research in this area is severely hampered by the lack of experimentally tractable in vitro model systems. To this end, here we describe a novel in vitro model for human pleomorphic liposarcoma. The cell line (LS2) is derived from a pleomorphic liposarcoma that utilizes Alternative Lengthening of Telomeres (ALT) mechanism of telomere maintenance, which may be particularly important in modulating the response of this tumor type to DNA damaging agents. We present detailed baseline molecular and genomic data, including genome wide copy number and transcriptome profiles, for this model compared to its parental tumor and a panel of liposarcomas covering multiple histologies. The model has retained essentially all of the detectable alterations in copy number that are seen in the parental tumor, and shows molecular karyotypic and expression profiles consistent with pleomorphic liposarcomas. We also demonstrate the utility of this model, together with two additional human liposarcoma cell lines, to investigate the relationship between topoisomerase 2A expression and the sensitivity of ALT-positive liposarcomas to doxorubicin. This model, together with its associated baseline data, provide a powerful new tool to develop treatments for this clinically poorly-tractable tumor, and to investigate the contribution that ALT makes to modulating sensitivity to DNA damaging chemotherapeutic agents such as doxorubicin.
Publication Title
Doxorubicin resistance in a novel in vitro model of human pleomorphic liposarcoma associated with alternative lengthening of telomeres.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
Illumina HiSeq 2500
Description
Melanoma is an aggressive neoplasm with increasing incidence that is classified by the NCI as a recalcitrant cancer, i.e., a cancer with poor prognosis, lacking progress in diagnosis and treatment. In addition to conventional therapy, melanoma treatment is currently based on targeting the BRAF/MEK/ERK signaling pathway and immune checkpoints. As drug resistance remains a major obstacle to treatment success, advanced therapeutic approaches based on novel targets are still urgently needed. We reasoned that the base excision repair enzyme Thymine DNA Glycosylase (TDG) could be such a target for its dual role in safeguarding the genome and the epigenome, by performing the last of the multiple steps in DNA demethylation. Overall design: Six samples : cells treated with shTDG and cells treated with shControl both in triplicates.
Publication Title
Thymine DNA glycosylase as a novel target for melanoma.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
We compared the gene expression profile from a group of children with T-cell acute lymphoblastic leukamia who remained in continuous complete remission (CCR) (n = 7) with that from a group who relapsed (n = 5), using Affymetrix HG-U133A arrays. Using the decision-tree based supervised learning algorithm Random Forest (RF), genes were ranked with respect to their ability to discriminate between patients who remained in CCR and those who relapsed. From the 300 top-ranked probe sets 9 genes were selected for further investigation and validation in an independent cohort of 25 T-ALL patients using quantitative real time polymerase chain reaction.
Publication Title
Identification of novel molecular prognostic markers for paediatric T-cell acute lymphoblastic leukaemia.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Subject
View Samples- Arabidopsis thaliana
- 14 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Lateral root initiation was used as a model system to study the mechanisms behind auxin-induced cell division. Genome-wide transcriptional changes were monitored during the early steps of lateral root initiation. Inclusion of the dominant auxin signaling mutant solitary root1 (slr1) identified genes involved in lateral root initiation that act downstream of the AUX/IAA signaling pathway. Interestingly, key components of the cell cycle machinery were strongly defective in slr1, suggesting a direct link between AUX/IAA signaling and core cell cycle regulation. However, induction of the cell cycle in the mutant background by overexpression of the D-type cyclin (CYCD3;1) was able to trigger complete rounds of cell division in the pericycle that did not result in lateral root formation. Therefore, lateral root initiation can only take place when cell cycle activation is accompanied by cell fate respecification of pericycle cells. The microarray data also yielded evidence for the existence of both negative and positive feedback mechanisms that regulate auxin homeostasis and signal transduction in the pericycle, thereby fine-tuning the process of lateral root initiation.
Publication Title
Cell cycle progression in the pericycle is not sufficient for SOLITARY ROOT/IAA14-mediated lateral root initiation in Arabidopsis thaliana.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Background: High density lipoprotein (HDL) protects the artery wall by removing cholesterol from lipid-laden macrophages. However, recent evidence suggests that it might also inhibit atherogenesis by combating inflammation. Methods and Results: To identify potential anti-inflammatory mechanisms, we challenged macrophages with lipopolysaccharide (LPS), an inflammatory microbial ligand for Toll-like receptor 4 (TLR4). HDL inhibited the expression of 33% (301 of 911) of the genes normally induced by LPS, microarray analysis revealed. One of its major targets was the type I interferon response pathway, a family of potent viral immunoregulators controlled by TLR4 and the TRAM/TRIF signaling pathway. Unexpectedly, HDLs ability to inhibit gene expression was independent of cellular cholesterol stores. Moreover, it was unaffected by downregulation of two ATP-binding cassette transporters, ABCA1 and ABCG1, that promote cholesterol efflux. To examine the pathways potential in vivo relevance, we used mice deficient in apolipoprotein (apo) A-I, HDLs major protein. After infection with Salmonella (a Gram-negative bacterium that expresses LPS), apoA-Ideficient mice had 6-fold higher plasma levels of interferon-beta-a key regulator of the type I interferon response than did wild-type mice. Conclusions: HDL inhibits a subset of LPS-stimulated macrophage genes that regulate the type I interferon response, and its action is independent of sterol metabolism. These findings raise the possibility that regulation of macrophage genes by HDL might link innate immunity and cardioprotection.
Publication Title
High-density lipoprotein suppresses the type I interferon response, a family of potent antiviral immunoregulators, in macrophages challenged with lipopolysaccharide.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 426 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The aim of the present study was to characterize the gene expression profile of the phosphodiesterase-4 inhibitor CHF6001 on top of inhaled triple therapy in sputum cells and whole blood of chronic bronchitis patients. Samples for analyses were collected from a multicenter, three-period, three-way, placebo-controlled, double-blind, complete block crossover study. Eligible patients underwent three, 32-day treatment periods during which they received CHF6001 800 or 1600 µg twice daily (total daily doses of 1600 or 3200 µg) or matching placebo, all via multi-dose dry-powder inhaler (NEXThaler). Treatment periods were separated by a 28–42 day washout. Eligible patients were male or female, ≥40 years of age, current or ex-smokers with a smoking history ≥10 pack-years, a diagnosis of COPD, post-bronchodilator forced expiratory volume in 1 second (FEV1) ≥30% and <70% predicted, ratio of FEV1 to forced vital capacity (FVC) <0.70, COPD Assessment Test score ≥10, and a history of chronic bronchitis (defined as chronic cough and sputum production for more than three months per year for at least two years) and treated with inhaled triple ICS/LABA/LAMA therapy for at least two months prior to enrollment. CHF6001 had no effect in blood, but a strong effect in sputum with 1471 and 2598 significantly differentially-expressed probe-sets relative to placebo (p-value adjusted for False Discovery Rate<0.05) for 800 and 1600µg , respectively. Functional enrichment analysis showed significant modulation of key inflammatory pathways involved in cytokine activity, pathogen-associated-pattern-recognition activity, oxidative stress and vitamin D with associated inhibition of downstream inflammatory effectors. A large number of pro-inflammatory genes coding for cytokines and matrix-metalloproteinases were significantly differentially expressed for both doses; the majority (>87%) were downregulated, including macrophage inflammatory protein-1-alpha and 1-beta, interleukin-27-beta, interleukin-12-beta, interleukin-32, tumor necrosis factor-alpha-induced-protein-8, ligand-superfamily-member-15, and matrix-metalloproteinases-7,12 and 14. In conclusion inhaled PDE4-Inhibition by CHF6001 on top of triple therapy in patients with chronic bronchitis patients significantly modulated key inflammatory targets and pathways in the lung but not in blood. Mechanistically these findings support a targeted effect in the lung while minimizing unwanted systemic class-effects
Publication Title
Sputum and blood transcriptomics characterisation of the inhaled PDE4 inhibitor CHF6001 on top of triple therapy in patients with chronic bronchitis.
Sample Metadata Fields
Specimen part, Treatment, Subject, Time
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GSE11092- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
CD34+ positively isolated from healthy donors (stimulated by G-CSF) with magnetic beads (after blood leukapheresis)
Publication Title
NA-Seq: a discovery tool for the analysis of chromatin structure and dynamics during differentiation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- IlluminaHiSeq2000
Description
RNA-seq analysis of human 293 Tet-off cells depleted of PTBP1 and UPF1 alone and in tandem with specific siRNAs. Overall design: siRNA-based depletion of PTBP1, UPF1, and PTBP1/UPF1 together, with a validated non-silencing siRNA as a control.
Publication Title
Polypyrimidine tract binding protein 1 protects mRNAs from recognition by the nonsense-mediated mRNA decay pathway.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 71 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Comprehensive analysis of gene expression in hematopoietic stem and progenitor cells from young and old mice.
Publication Title
Quiescent hematopoietic stem cells accumulate DNA damage during aging that is repaired upon entry into cell cycle.
Sample Metadata Fields
Sex, Age, Specimen part, Time
View Samples- Arabidopsis thaliana
- 12 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
The number of cells in an organ is a major factor for the determination of organ size. However, genetic basis of cell number determination is not well understood. Three grandifolia-D (gra-D) mutants of Arabidopsis thaliana developed huge leaves containing two- to three-fold increased number of cells of the wild type. Tiling array and microarray analysis of gra-D mutants suggested that genes found in a lower part of chromosome 4 were upregulated, suggesting the occurrence of segmental chromosomal duplications in the gra-D mutants. These region contain positive regulators of cell proliferation such as AINTEGUMENTA (ANT) and cyclin genes such as CYCD3;1.
Publication Title
Impact of segmental chromosomal duplications on leaf size in the grandifolia-D mutants of Arabidopsis thaliana.
Sample Metadata Fields
Specimen part
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