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GSE133513
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
View Samples- Mus musculus
- 4 Downloadable Samples
Illumina HiSeq 2000
Description
We report that phosphorylated ribosomes can be immunoprecipitated from mouse brain homogenates, resulting in enrichment of transcripts expressed in activated neurons. Overall design: Mice were either injected with a concentrated salt solution or vehicle, hypothalami dissected, and phosphorylated ribosomes immunoprecipitated. RNA was sequenced from the input and IP for each condition (4 samples total).
Publication Title
Molecular profiling of activated neurons by phosphorylated ribosome capture.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- IlluminaHiSeq2000
Description
RNA sequencing libraries were made for A-498 and 786-O to detect the transcripts regulated by the lincRNA comparing knockdown and the non-targeting control. Overall design: Two siRNAs were designed, non-target control and the siRNAs were introduced to the cell lines A-498 and 786-O separately by Lipofectamine 2000. After 16 hours total RNA were extracted. Barcoded cDNA libraries were then prepared from total RNA using the Illumina TruSeq RNAseq kit, and sequenced (single-end 36-bp reads) on an Illumina HiSeq instrument.
Publication Title
Novel lincRNA SLINKY is a prognostic biomarker in kidney cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Understanding how lung progenitor cells balance
Publication Title
Integrated proteomic and transcriptomic profiling of mouse lung development and Nmyc target genes.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
comparison of expression of wildtype lungs and lungs with hypomorphic expression of nmyc. the lungs were pooled from several biological samples. The hypomorphoic mutant was orignally published in Moens CB et al [PMID: 1577267]. this is part of a larger collection of data comparing nmyc misexpression in the lung (gain of fucntion) and protein expression in the hypomorphic lungs.
Publication Title
Integrated proteomic and transcriptomic profiling of mouse lung development and Nmyc target genes.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 101 Downloadable Samples
- Illumina HiSeq 2500
Description
The experiment aimed at determing the influence of mast cell deficiency on the transcriptome of skin-infiltrating leukocytes in K14HPV16 mice at 2month and 6month of age. Overall design: Skin-inflitrating leucocytes were FACS-purified from mast cell proficient (Mcpt5-Cre-) and mast cell deficient (Mcpt5-Cre+) K14HPV16 mice. Mast cells (CD117 high, FCeR1 high) were excluded from the sorting gate. In order to control for minimal mast cell contamination during sorting from K14HPV16 Mcpt5-Cre- skin, mast cell signature transcripts were identified by comparing transcriptomes of samples fromK14HPV16 Mcpt5-Cre- mice in which mast cells were flow cytometrically included vs excluded.
Publication Title
Although Abundant in Tumor Tissue, Mast Cells Have No Effect on Immunological Micro-milieu or Growth of HPV-Induced or Transplanted Tumors.
Sample Metadata Fields
Age, Specimen part, Subject
View Samples- Mus musculus
- 38 Downloadable Samples
- Illumina HiSeq 2500
Description
RNA seq was used to compare the expression profile of macrophages in presence and absense of mast cells. MB49 cells were injected i.d. into Mcpt5-Cre+ R26DTA animals and cre-negative littermates. Macrophages were sorted at 20 d.p.i. Overall design: Macrophage RNA profiles of MB49 TAMs (tumor-associated macrophages), harvested at 20 d.p.i. in MC-Proficient and MC-deficient animals
Publication Title
Although Abundant in Tumor Tissue, Mast Cells Have No Effect on Immunological Micro-milieu or Growth of HPV-Induced or Transplanted Tumors.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 112 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Molecular subtypes of metastatic colorectal cancer are associated with patient response to irinotecan-based therapies.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 61 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We report that previously described molecular subtypes of colorectal cancer are associated with the response to therapy in patients with metastatic disease. We also identified a patient population with high FOLFIRI sensitivity, as indicated by their 2.7-fold longer overall survival when treated with FOLFIRI, as first-line regimen, instead of FOLFOX. Our results demonstrate the interest of molecular classifications to develop tailored therapies for patients with metastatic colorectal cancer.
Publication Title
Molecular subtypes of metastatic colorectal cancer are associated with patient response to irinotecan-based therapies.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 51 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We report that previously described molecular subtypes of colorectal cancer are associated with the response to therapy in patients with metastatic disease. We also identified a patient population with high FOLFIRI sensitivity, as indicated by their 2.7-fold longer overall survival when treated with FOLFIRI, as first-line regimen, instead of FOLFOX. Our results demonstrate the interest of molecular classifications to develop tailored therapies for patients with metastatic colorectal cancer.
Publication Title
Molecular subtypes of metastatic colorectal cancer are associated with patient response to irinotecan-based therapies.
Sample Metadata Fields
Sex, Age
View Samples