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GSE115313
Homo sapiens
27 Downloadable Samples
Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
This is a transcriptomics analysis contributing to a bigger project that tries to shed light on the role of type 2 diabetes mellitus (T2DM) as a risk factor for colon cancer (CC). Here we present a gene expression screening of paired tumor and normal colon mucosa samples in a cohort of 42 CC patients, 23 of them with T2DM. Using gene set enrichment, we identified an unexpected overlap of pathways over-represented in diabetics compared to non-diabetics, both in tumor and normal mucosa, including diabetes-related metabolic and signaling processes. An integration with other -omic studies suggests that in diabetics, the local micro-environment in normal colon mucosa may be a factor driving field cancerization which may promote carcinogenesis. Several of these pathways converged on the tumor initiation axis TEAD/YAP-TAZ. Cell culture studies confirmed that high glucose concentrations upregulate this pathway in non-tumor colon cells. In conclusion, diabetes is associated to deregulation of cancer-related processes in normal colon mucosa adjacent to tissue which has undergone a malignant transformation. These data support the existence of the field of cancerization paradigm in diabetes and set a new framework to study link between diabetes and cancer.
Publication Title
Molecular evidence of field cancerization initiated by diabetes in colon cancer patients.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 1 Downloadable Sample
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
This is a transcriptomics analysis contributing to a bigger project that tries to shed light on the role of type 2 diabetes mellitus (T2DM) as a risk factor for colon cancer (CC). Here we present a gene expression screening of 7 colon tumor xenograft samples, 2 with diabetic mice and 5 with normal blood glucose levels. For xenograft model details see: Prieto I, et al. (2017) Colon cancer modulation by a diabetic environment: A single institutional experience. PLoS One 12(3):e0172300
Publication Title
Molecular evidence of field cancerization initiated by diabetes in colon cancer patients.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 37 Downloadable Samples
Illumina HiSeq 2000
Description
The Sanaria® PfSPZ Vaccine can confer sterilizing protection against liver stage infection by Plasmodium falciparum (Pf) in malaria naïve individuals. The vaccine consists of aseptically purified irradiated Pf sporozoites. The PfSPZ Vaccine trial in Mali was the first to evaluate the safety and efficacy of this vaccine in a malaria endemic region. Vaccinees received five doses of 2.7 X 105 irradiated sporozoites and the efficacy was measured against naturally occurring Pf Infections in Malian adults during the malaria transmission season. Overall design: 44 samples from 2 time points, pre-vaccination (Day -7) and post-vaccination (Day 143), for 22 Malian adult participants ( 5 placebo controls and 17 vaccine recipients). 11 of the vaccinated participants remained infection free over the subsequent malaria transmission season.
Publication Title
γδ T Cells Are Required for the Induction of Sterile Immunity during Irradiated Sporozoite Vaccinations.
Sample Metadata Fields
Subject, Time
View Samples- Homo sapiens
- 228 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: Blocking the action of the pro-inflammatory cytokine interleukin-1 (IL-1) reduces beta-cell secretory dysfunction and apoptosis in vitro, diabetes incidence in animal models of Type 1 diabetes mellitus (T1D), and glycaemia via improved beta-cell function in patients with T2D. We hypothesised that anakinra, a recombinant human IL-1 receptor antagonist, improves beta-cell function in patients with new-onset T1D. Methods: In an individually randomised, two-group parallel trial involving 14 European tertiary referral centers, 69 patients aged 18-35 with T1D, < 12 weeks of symptoms, and standard mixed meal test (MMT) stimulated C-peptide 200 pM were enrolled between January, 2009 and July, 2011 and assigned by centralised computer-generated blocked randomisation with locked computer-file concealment to treatment with 100 mg anakinra (n=35) subcutaneously once daily or placebo (n=34) for 9 months as add-on to conventional therapy. Participants and care-givers, but not data monitoring unit, were masked to group assignment. The primary end-point was change in the two-hour area-under-the-curve C-peptide response to MMT, and secondary end-points changes in insulin requirements, glycaemia, and inflammatory markers at one, three, six, and nine months. Findings: The study was prematurely terminated due to slow accrual and is closed to follow-up. No interim analysis was performed. Ten patients withdrew in the anakinra and eight in the placebo arm, leaving 25 and 26 patients to be analysed, respectively. There was no statistical difference in adverse event category reporting between arms. Interpretation: Anakinra-treatment in T1D was safe, but the trial failed to meet primary and secondary outcome measures.
Publication Title
Interleukin-1 antagonism moderates the inflammatory state associated with Type 1 diabetes during clinical trials conducted at disease onset.
Sample Metadata Fields
Subject, Time
View Samples- Homo sapiens
- 187 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: Blocking the action of the pro-inflammatory cytokine interleukin-1 (IL-1) reduces beta-cell secretory dysfunction and apoptosis in vitro, diabetes incidence in animal models of Type 1 diabetes mellitus (T1D), and glycaemia via improved beta-cell function in patients with T2D. We hypothesised that canakinumab, a monoclonal antibody to IL-1B, improves beta-cell function in patients with new-onset T1D. Methods: In an individually randomised, two-group parallel trial involving 12 sites in US, 69 patients aged 6-45 with T1D, < 12 weeks of symptoms, and assigned by centralised computer-generated blocked randomisation with locked computer-file concealment to treatment with 2 mg/kg (maximum 300 mg) canakinumab (n=45) or placebo (n=22) monthly for 12 months as add-on to conventional therapy. Participants and care-givers, but not data monitoring unit, were masked to group assignment. The primary end-point was change in the two-hour area-under-the-curve C-peptide response to MMT 12 months.
Publication Title
Interleukin-1 antagonism moderates the inflammatory state associated with Type 1 diabetes during clinical trials conducted at disease onset.
Sample Metadata Fields
Subject, Time
View Samples- Homo sapiens
- 320 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
New measures are needed to predict type 1 diabetes disease trajectory. We have developed a sensitive array-based bioassay whereby patient plasma is used to induce transcription in healthy reporter leukocytes. Here we report a refined gene ontology-based inflammatory index (I.I.359) that is based upon expression levels of 359 transcripts identified in cross-sectional studies of new onset Type 1 diabetes patients and controls, where higher scores reflect greater inflammatory bias. We examined the relationship between I.I.359 measured at onset and the post-onset disease course in local patients as well as participants of the TrialNet CTLA4-Ig trial. In untreated patients, I.I.359 at baseline was highly variable and exhibited a significant inverse relationship with stimulated C-peptide AUC at 3, 6, 12, 18 and 24 months post-onset. Further, duration of the post-onset partial remission was negatively related to baseline I.I.359 and positively associated with the peripheral abundance of activated regulatory T cells (CD4+/CD45RA-/FoxP3high).
Publication Title
Innate immune activity as a predictor of persistent insulin secretion and association with responsiveness to CTLA4-Ig treatment in recent-onset type 1 diabetes.
Sample Metadata Fields
Cell line, Time
View Samples- Homo sapiens
- 128 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Standard of hygiene and immune adaptation in newborn infants.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 113 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
The prevalence of immune-mediated diseases such as allergies and autoimmune diseases is on the rise in the developed world. Microbial exposure is known to modulate the risk for these diseases. In order to explore differences in the gene expression patterns induced in utero in infants born in contrasting standards of living and hygiene, we collected umbilical cord blood RNA samples from full-term newborn infants born with normal vaginal delivery in Finland (modern society), Estonia (rapidly developing society) and the Republic of Karelia, Russia (poor economical conditions). Transcriptomic profiles were analyzed using whole genome microarrays including gender, gestational age, birth month and HLA allele genotype as confounding variables in the analysis. The data revealed that the whole blood transcriptome of Finnish and Estonian neonates differ from their Karelian counterparts. Samples from Karelian infants had an increase in transcripts associated with LPS induction and bacterial sepsis observed in 1-year-old infants in earlier studies. The results suggest exposure to toll like receptor (TLR) ligands and a more matured immune response in infants born in Petrozavodsk compared to the Finnish and Estonian infants. These results further support the concept of a conspicuous plasticity in the developing immune system: the environmental factors that play a role in the susceptibility/protection towards immune-mediated diseases begin to shape the neonatal immunity already in utero and direct the maturation of both the adaptive and the innate immune responses in accordance with the surrounding microbial milieu.
Publication Title
Standard of hygiene and immune adaptation in newborn infants.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
The prevalence of immune-mediated diseases such as allergies and autoimmune diseases is on the rise in the developed world. Microbial exposure is known to modulate the risk for these diseases. In order to explore differences in the gene expression patterns induced in utero in infants born in contrasting standards of living and hygiene, we collected umbilical cord blood RNA samples from full-term newborn infants born with normal vaginal delivery in Finland (modern society), Estonia (rapidly developing society) and the Republic of Karelia, Russia (poor economical conditions). Transcriptomic profiles were analyzed using whole genome microarrays including gender, gestational age, birth month and HLA allele genotype as confounding variables in the analysis. The data revealed that the whole blood transcriptome of Finnish and Estonian neonates differ from their Karelian counterparts. Samples from Karelian infants had an increase in transcripts associated with LPS induction and bacterial sepsis observed in 1-year-old infants in earlier studies. The results suggest exposure to toll like receptor (TLR) ligands and a more matured immune response in infants born in Petrozavodsk compared to the Finnish and Estonian infants. These results further support the concept of a conspicuous plasticity in the developing immune system: the environmental factors that play a role in the susceptibility/protection towards immune-mediated diseases begin to shape the neonatal immunity already in utero and direct the maturation of both the adaptive and the innate immune responses in accordance with the surrounding microbial milieu.
Publication Title
Standard of hygiene and immune adaptation in newborn infants.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The Wnt/beta-catenin pathway is required for the development of leukemia stem cells in MLL-AF9 AML.
Publication Title
KRas(G12D)-evoked leukemogenesis does not require β-catenin.
Sample Metadata Fields
Specimen part
View Samples