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GSE52735
Homo sapiens
37 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The objective is to generate a robust and validated predictor profile for chemotherapy response in patients with mCRC using microarray gene expression profiles of primary colorectal cancer tissue.
Publication Title
Gene expression profile predictive of response to chemotherapy in metastatic colorectal cancer.
Sample Metadata Fields
Disease, Disease stage
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
The iron chelator deferasirox is widely used in patients with iron overload. Patients with low-grade myelodysplastic syndromes (MDS) get transfusion dependency and need to be treated with deferasirox to avoid iron overload. Moreover, in some patients an increase in both erythroid and platelets have been observed after deferasirox therapy. However, the mechanisms involved in these clinical findings are poorly understood. The aim of this work was to analyze, in patients treated with deferasirox, the changes in the gene expression profile after receiving the treatment. A total of fifteen patients with the diagnosis of low-grade MDS were studied. Microarrays were carried out in RNA from peripheral blood before and after 14 weeks of deferasirox therapy. Changes in 1,457 genes and 54 miRNAs were observed: deferasirox induced the downregulation of genes related to the Nf kB pathway leading of an overall inactivation of this pathway. In addition, the iron chelator also downregulated gamma interferon. Altogether these changes could be related to the improvement of erythroid response observed in these patients after therapy. Moreover, the inhibition of NFE2L2/ NRF2, which was predicted in silico, could be playing a critical role in the reduction of reactive oxygen species (ROS). Of note, miR-125b, overexpressed after deferasirox treatment, could be involved in the reduced inflammation and increased hematopoiesis observed in the patients after treatment. In summary this study shows, for the first time, the mechanisms that could be governing deferasirox impact in vivo.
Publication Title
Genome-wide transcriptomics leads to the identification of deregulated genes after deferasirox therapy in low-risk MDS patients.
Sample Metadata Fields
Specimen part, Disease, Treatment, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
IlluminaHiSeq2000
Description
We utilized whole genome sequencing of mRNA (RNA-seq) to understand the extent to which the senescence-associated secretory phenotype is regulated by p38MAPK Overall design: Examination of replicates of young, senescent or p38MAPK-inhibited senescent BJ human foreskin fibroblasts.
Publication Title
p38MAPK plays a crucial role in stromal-mediated tumorigenesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Clariom S Human array (clariomshuman)
Description
Bitter taste receptors (T2Rs) are typical G-protein coupled receptors expressed in various tissue where they are involved in the regulation of physiological processes, thus suggesting a wider function in sensing microenvironment. We analyzed their expression and role in acute myeloid leukemia (AML). AML cells express functional T2Rs and their stimulation with the agonist, denatonium benzoate, substantially modified the AML cell transcriptomic profile and functions. GEP analysis identified relevant cellular processes affected by denatonium treatment in AML, including cell cycle, survival, migration and metabolism. More precisely, T2R activation reduced proliferation by inducing cell cycle arrest in G0/G1 phase or induced apoptosis via caspase cascade activation; impaired AML cell motility and migratory capacity; inhibited cellular respiration by decreasing glucose uptake and oxidative phosphorylation.
Publication Title
Denatonium as a Bitter Taste Receptor Agonist Modifies Transcriptomic Profile and Functions of Acute Myeloid Leukemia Cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Malignant progression in cancer has been associated with the emergence of populations of tumor-initiating cells (TIC) endowed with capabilities for unlimited self-renewal, survival under stress and establishment of distant metastases. Additionally, the acquisition of invasive properties driven by the genetic program known as epithelialmesenchymal transition (EMT) may be an essential step in the evolution of neoplastic cells into fully metastatic populations. A widely accepted paradigm is that EMT potentiates tumor cell self-renewal and metastatic behaviour. Here we describe a cellular model in which a clonal population enriched in TIC expresses a genetic program distinct from a second population with traits of stable EMT, and in which both populations cooperate for enhanced local invasiveness and metastasis. Induction of the TIC-enriched population to undergo EMT by several stimuli or by constitutive overexpression of the transcription factor SNAI1 engaged a mesenchymal program while suppressing the CSC program. This suggests that TIC and EMT, contrary to current paradigms, correspond to alternative states. Furthermore, diffusible factors secreted by the population with EMT traits also induced mesenchymal reprogramming of the population enriched in CSCs. Local invasiveness in vitro and lung colonization in vivo of the TIC-enriched population was enhanced by co-injection with the EMT-trait population, and expanded the range of organs to which it metastasized. Thus, in our model, relatively stable TIC and EMT phenotypes reflect alternative genetic programs expressed by distinct clonal populations. We also suggest that dynamic cooperation between tumor subpopulations displaying either TIC or EMT traits may be a general mechanism driving local invasiveness and metastasis.
Publication Title
Epithelial-mesenchymal transition can suppress major attributes of human epithelial tumor-initiating cells.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
hCLE/C14orf166/RTRAF, DDX1 and HSPC117 are components of cytoplasmic mRNA-transporting granules kinesin-associated in dendrites. They have also been found in cytoplasmic ribosome-containing RNA granules that transport specific mRNAs halted for translation until specific neuronal signals renders them accessible to the translation machinery. hCLE associates to DDX1, HSPC117 and FAM98B in HEK293T cells and all four proteins bind to cap analog-containing resins. Competition and elution experiments indicate that binding of hCLE complex to cap resins is independent of eIF4E; the cap-binding factor needed for translation. Purified hCLE free of its associated proteins binds cap with low affinity suggesting that its interacting proteins modulate its cap association. hCLE silencing reduces hCLE accumulation and that of its interacting proteins and decreases mRNA translation. hCLE-associated RNAs have been isolated and sequenced; RNAs involved in mRNA translation are specifically associated. The data suggest a positive role of hCLE complex modulating mRNA translation. Overall design: Standard RNA-seq protocol was applied for comparing two sample types (HEK293T cells transfected with hCLE-TAP plasmid or empty TAP) with two biological replicates each. More than 20 million single-end, strand-specific 50 nt reads were generated for each sample.
Publication Title
hCLE/RTRAF-HSPC117-DDX1-FAM98B: A New Cap-Binding Complex That Activates mRNA Translation.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The anaphylatoxin C5a is a potent mediator of innate immunity and promotes inflammation via its receptor C5aR1 upon complement system activation danger-associated molecular patterns. Both C5a and C5aR1 are thought to be contributing factors in inflammatory and infectious conditions of the bone. Bone fracture healing, for example, was significantly improved when applying a C5aR1-antagonist in a rodent model of severe systemic inflammation and osteoblasts were found to be target cells for C5a in this setting. Interestingly, osteoblasts up-regulate C5aR1 during osteogenic differentiation and after bone injury. Further, C5a induces inflammatory cytokines, such as IL-6, and the osteoclastogenic mediator RANKL in osteoblasts. However, the molecular mechanisms underlying C5a-C5aR1 signaling axis in osteoblasts remain unclear, and further targets of C5a are still elusive. Using microarray analysis, we analyzed intracellular events following C5aR1 activation in osteoblasts and defined up- or down-regulated genes and their belonging biological pathways.
Publication Title
C5aR1 interacts with TLR2 in osteoblasts and stimulates the osteoclast-inducing chemokine CXCL10.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 144 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background. Most colorectal cancers (CRC) arise in a progression through adenoma to carcinoma phenotypes as a consequence of altered genetic information. Clinical progression of CRC may occur in parallel with distinctive signaling alterations. We designed multidirectional analyses integrating microarray-based data with biostatistics and bioinformatics to elucidate the signaling and metabolic alterations underlying CRC development in the adenoma-carcinoma sequence. Methodology/Principal Findings. Studies were performed on normal mucosa, adenoma, and CRC samples obtained during surgery or colonoscopy. Collections of cryostat sections prepared from the tissue samples were evaluated by a pathologist to control the relative cell type content. RNA was isolated from 105 macro- and 40 microdissected specimens. The measurements were done using Affymetrix GeneChip HG-U133plus2, and probe set data were generated using two normalization algorithms: MAS5 and GCRMA with LVS. The data were evaluated using pair-wise comparisons and data decomposition into SVD modes. The method selected for the functional analysis used the Kolmogorov-Smirnov test. Based on a consensus of the results obtained by two tissue handling procedures, two normalization algorithms, and two probe set sorting criteria, we identified six KEGG signaling and metabolic pathways (cell cycle, DNA replication, p53 signaling pathway, purine metabolism, pyrimidine metabolism, and RNA polymerase) that are significantly altered in both macro- and microdissected tumor samples compared to normal colon. On the other hand, pathways altered between benign and malignant tumors were identified only in the macrodissected tissues. Conclusion/Significance. Multidirectional analyses of microarray data allow the identification of essential signaling alterations underlying CRC development. Although the proposed strategy is computationally complex and laborintensive, it may reduce the number of false results.
Publication Title
Modeling oncogenic signaling in colon tumors by multidirectional analyses of microarray data directed for maximization of analytical reliability.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Arabidopsis thaliana
- 24 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
We performed a transcriptomic analysis of Pi starvation responses in Arabidopsis thaliana (Columbia-0) wild type plants under phosphate starvation stress and in plants with altered PHR1(-like) activity, comparing mutants of phr1 and phr1-phl1 grown in phosphate-lacking medium. Results show the central role of PHR1 and functionally redundant members of its family in the control of transcriptional responses to Pi starvation.
Publication Title
A central regulatory system largely controls transcriptional activation and repression responses to phosphate starvation in Arabidopsis.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
We performed a transcriptomic analysis of Pi starvation responses in Arabidopsis thaliana (Columbia-0) phr1 mutant plants expressing PHR1 in presence of cicloheximide, that inhibit protein translation, thus preventing any effect of PHR1 on the expression of indirect targets. Results show the primary target genes of PHR1 in the responses to Pi starvation.
Publication Title
A central regulatory system largely controls transcriptional activation and repression responses to phosphate starvation in Arabidopsis.
Sample Metadata Fields
No sample metadata fields
View Samples