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GSE45626
Homo sapiens
33 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Insulin-like growth factor receptor-1 (IGF-1R) inhibition could be a relevant therapeutic approach in small cell lung cancer (SCLC) given the importance of an IGF-1R autocrine loop and its role in DNA damage repair processes. We assessed IGF-1R and pAkt protein expression in 83 SCLC human specimens. The efficacy of R1507 (a monoclonal antibody directed against IGF-1R) alone or combined with cisplatin or ionizing radiation (IR) was evaluated in H69, H146 and H526 cells in vitro and in vivo. Innovative genomic and functional approaches were conducted to analyze the molecular behavior under the different treatment conditions. A total of 53% and 37% of human specimens expressed IGF-1R and pAkt, respectively. R1507 demonstrated single agent activity in H146 and H526 cells but not in H69 cells. R1507 exhibited synergistic effects with both Cisplatin and IR in vitro. The triple combination R1507-Cisplatin-IR led to a dramatic delay in tumor growth compared to Cisplatin-IR in H526 cells. Analyzing the apparent absence of antitumoral effect of R1507 alone in vivo, we observed a transient reduction of IGF-1R staining intensity in vivo, concomitant to the activation of multiple cell surface receptors and intracellular proteins involved in proliferation, angiogenesis and survival. Finally, we identified that the nucleotide excision repair pathway (NER) was mediated after exposure to R1507-CDDP and R1507-IR in vitro and in vivo. In conclusion, adding R1507 to the current standard Cisplatin-IR doublet reveals remarkable chemo- and radiosensitizing effects in selected SCLC models and warrants to be investigated in the clinical setting.
Publication Title
IGF-1R targeting increases the antitumor effects of DNA-damaging agents in SCLC model: an opportunity to increase the efficacy of standard therapy.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 27 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Analysis of gene-expression profiles by microarrays can be very useful to characterize new potential candidate genes, key regulatory networks, and to define phenotypes or molecular signatures to improve the diagnosis or classification of the disease. We have used this approach in the study of one of the major causes of allergic diseases in Mediterranean countries, the olive pollen response, in order to find differential molecular markers among five clinical groups, Non-allergic, Asymptomatic, Allergic but not to olive pollen, Non-treated, olive pollen allergic patients and Olive pollen allergic patients (under specific-immunotherapy). The results of gene-expression by principal components analysis (PCA) clearly showed five clusters of samples that correlated with the five clinical groups. Analysis of differential gene-expression by multiple testing, and functional analysis by KEGG and Gene-Ontology revealed differential genes and pathways among the 5 clinical groups.
Publication Title
Differential gene-expression analysis defines a molecular pattern related to olive pollen allergy.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 42 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Analysis of gene-expression profiles with microarrays can be very useful to dissect specific responses and to characterize with a global view, new elements for improving the diagnosis, treatment and understanding of allergic diseases. We have used this approach for studying the olive pollen response, taking advantage our previous results of T-cell epitope mapping on Ole e 1 molecule (the major allergen from olive pollen) in order to analyze the stimuli influence on the gene-expression of olive pollen allergic patients. Peripheral blood mononuclear cells (PBMCs) from 6 healthy controls and 6 allergic subjects were stimulated 24 hours with olive pollen stimuli: Ole e 1 molecule and two Ole e 1 peptides previously defined as P2+3 (aa10-31), mainly recognized by non-allergic subjects (possible immunoregulatory epitope) and P10+12+13 (aa90-130), immunodominant T-cell epitope. RNA extracted from basal and stimulated PBMCs was analyzed by HuGeU133 plus 2.0 GeneChip, Affymetrix (38.500genes). After assessment of data quality by standard quality checks and principal components analysis (PCA), differential gene-expression by experimental conditions was performed by multiple testing, using microarrays specific software. Differences in functional analysis were performed by KEGG, for pathways and Gene-Ontology for biological process. The results of gene-expression by PCA showed differential clusters that correlated with the experimental conditions from samples of allergic patients. Analysis of differential gene-expression by multiple testing, and functional analysis by KEGG and Gene-Ontology revealed differential genes and pathways among the 4 experimental conditions.
Publication Title
Therapeutic targets for olive pollen allergy defined by gene markers modulated by Ole e 1-derived peptides.
Sample Metadata Fields
Specimen part, Disease
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Hepatocellular carcinoma (HCC) is an important cause of morbidity and mortality worldwide. Although the risk factors of human HCC are well known, the molecular characterization of this disease is complex, and treatment options in general remain poor. The use of rodent models to study human cancer has been extensively pursued both through genetically engineered rodents and rodent models used in carcinogenicity and toxicology studies. In particular, the B6C3F1 mouse used in the National Toxicology Program (NTP) 2-year bioassay has been used to evaluate the carcinogenic effects of environmental and occupational chemicals, and other compounds. The high incidence of spontaneous HCC in the B6C3F1 mouse has challenged its use as a model for chemically induced HCC in terms of relevance to the human disease. Using global gene expression profiling, we identify the dysregulation of several mediators similarly altered in human HCC, including re-expression of fetal oncogenes, upregulation of protooncogenes, downregulation of tumor suppressor genes, and abnormal expression of cell cycle mediators, growth factors, apoptosis regulators, and angiogenesis and extracellular matrix remodeling factors. Although important differences in etiology and pathogenesis remain between human and mouse HCC, there are important similarities in global gene expression and the types of signaling networks dysregulated in mouse and human HCC. These data provide further relevance for the use of this model in hazard identification of compounds with potential human carcinogenicity risk, and may help in better understanding mechanisms of tumorigenesis due to chemical exposure in the NTP 2-year carcinogenicity bioassay.
Publication Title
Global gene profiling of spontaneous hepatocellular carcinoma in B6C3F1 mice: similarities in the molecular landscape with human liver cancer.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Introduction: Lung cancer is the leading cause of cancer-related death in people. There are several chemically induced and genetically modified mouse models used to study lung cancer. We hypothesized that spontaneous murine (B6C3F1) lung tumors can serve as a model to study human non-small cell lung cancer (NSCLC). Methods: RNA was extracted from untreated 2-year-old B6C3F1 mouse spontaneous lung (SL) tumors and age-matched normal lung tissue from a chronic inhalation NTP study. Global gene expression analysis was performed using Affymetrix Mouse Genome 430 2.0 GeneChip arrays. After data normalization, for each probe set, pairwise comparisons between groups were made using a bootstrap t-test while controlling the mixed directional false discovery rate (mdFDR) to generate a differential gene expression list. IPA, KEGG, and EASE software tools were used to evaluate the overrepresented cancer genes and pathways. Results: MAPK and TGF-beta pathways were overrepresented within the dataset. Almost all of the validated genes by quantitative real time RT-PCR had comparable directional fold changes with the microarray data. The candidate oncogenes included Kras, Braf, Raf1, Id2, Hmga1, Cks1b, and Foxf1. The candidate tumor suppressor genes included Rb1, Cdkn2a, Hnf4a, Tcf21, Ptprd, Hpgd, Hopx, Ogn, Id4, Hoxa5, Smad6, Smad7, Zbtb16, Cyr61, Dusp4, and Ifi16. In addition, several genes important in lung development were also differentially expressed, such as Smad6, Hopx, Sox4, Sox9 and Mycn. Conclusion: In this study, we have demonstrated that several cancer genes and signaling pathways relevant for human NSCLC were similarly altered in spontaneous murine lung tumors.
Publication Title
Differential transcriptomic analysis of spontaneous lung tumors in B6C3F1 mice: comparison to human non-small cell lung cancer.
Sample Metadata Fields
Disease, Disease stage
View Samples- Homo sapiens
- 2 Downloadable Samples
Illumina HiScanSQ
Description
We used next generation sequencing to analyze the gene expression changes in U2OS osteosarcoma cells expressing shRNA targeting the promyelocytic leukemia (PML) gene transcripts Overall design: cDNA libraries of U2OS cells expressing control shRNA or shRNA targeting PML were generated from one biological replicate
Publication Title
PML nuclear bodies contribute to the basal expression of the mTOR inhibitor DDIT4.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To determine if aberrant activation of endothelin-1 (Et1) could lead to the dysregulation of many downstream genes, we exposed fibroblasts to exogenous ET1 peptide and assayed for transcriptional changes by microarray. Mouse dermal fibroblasts were treated with exogenous Et1 peptide for 24 hours. ET1 treatment resulted in significant expression changes primarily downregulation of a number of genes. In particular, Tgf2 and Tgf3 were among the downregulated genes, which in turn alter the expression status of their many target genes. These data suggest that the stable silencing of Et1 is important for the phenotypic stability of dermal fibroblasts, and perhaps many other cell types as well.
Publication Title
Localized methylation in the key regulator gene endothelin-1 is associated with cell type-specific transcriptional silencing.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 320 Downloadable Samples
- NextSeq 500
Description
Certain neuron types fire spontaneously at high rates, an ability that is crucial for their function in brain circuits. The spontaneously active GABAergic neurons of the substantia nigra pars reticulata (SNr), a major output of the basal ganglia, provide tonic inhibition of downstream brain areas. A depolarizing "leak" current supports this firing pattern, but its molecular basis remains poorly understood. To understand how SNr neurons maintain tonic activity, we used single-cell RNA sequencing to determine the transcriptome of individual SNr neurons. We discovered that SNr neurons express the sodium leak current, NaLCN and that SNr neurons lacking NaLCN have impaired spontaneous firing. Overall design: RNA sequencing profiles from 87 GFP-positive GABAergic SNr neurons and 9 GFP-negative SNr cells were carried out. However only 80 samples that passed initial quality control and that were included in the data processing are represented in this record.
Publication Title
The leak channel NALCN controls tonic firing and glycolytic sensitivity of substantia nigra pars reticulata neurons.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 101 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Th1 and Th2 cells arise from a common precursor cell in response to triggering through the TCR and cytokine receptors for IL-12 or IL-4. This leads to activation of complex signaling pathways, which are not known in detail. Disturbances in the balance between type 1 and type 2 responses can lead to certain immune-mediated diseases. Thus, it is important to understand how Th1 and Th2 cells are generated. To clarify the mechanisms as to how IL-12 and IL-4 induce Th1 and Th2 differentiation and how TGF-beta can inhibit this process, we have used oligonucleotide arrays to examine the early polarization of Th1 and Th2 cells in the presence and absence of TGF-beta after 0, 2, 6 and 48 hours of polarization.
Publication Title
Identification of novel genes regulated by IL-12, IL-4, or TGF-beta during the early polarization of CD4+ lymphocytes.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 16 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
17-estradiol (E2) exerts complex and context-dependent effects in pulmonary hypertension. In hypoxia-induced pulmonary hypertension (HPH), E2 attenuates lung vascular remodeling through estrogen receptor (ER)-dependent effects; however, ER target genes in the hypoxic lung remain unknown. In order to identify the genome regulated by the E2-ER axis in the hypoxic lung, we performed a microarray analysis in lungs from HPH rats treated with E2 (75 mcg/kg/d) ER-antagonist ICI182,780 (3 mg/kg/d). Untreated HPH rats and normoxic rats served as controls. Using a false discovery rate of 10%, we identified a significantly differentially regulated genome in E2-treated vs. untreated hypoxia rats. Genes most up-regulated by E2 encoded matrix metalloproteinase 8, S100 calcium binding protein A8, and IgA Fc receptor; genes most down-regulated by E2 encoded olfactory receptor 63, secreted frizzled-related protein 2, and thrombospondin 2. Several genes affected by E2 changed in the opposite direction after ICI182,780 co-treatment, indicating an ER-regulated genome in HPH lungs. The bone morphogenetic protein antagonist Grem1 (gremlin 1) was up-regulated by hypoxia, but found to be among the most down-regulated genes after E2 treatment. Gremlin 1 protein was reduced in E2-treated vs. untreated hypoxic animals, and ER-blockade abolished the inhibitory effect of E2 on Grem1 mRNA and protein. In conclusion, E2 ER-dependently regulates several genes involved in proliferative and inflammatory processes during hypoxia. Gremlin 1 is a novel target of the E2-ER axis in HPH. Understanding the mechanisms of E2 gene regulation in HPH may allow for selectively harnessing beneficial transcriptional activities of E2 for therapeutic purposes.
Publication Title
Estrogen receptor-dependent attenuation of hypoxia-induced changes in the lung genome of pulmonary hypertension rats.
Sample Metadata Fields
Treatment
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