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accession-icon GSE134114
Effect of NOTCH-γ-secretase inhibitor LY3039478 therapy on patient derived xenograft (PDX) mouse model of intrahepatic cholangiocarcinoma
  • organism-icon Homo sapiens
  • sample-icon 11 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Transcriptome Array 2.0 (hta20)

Description

Intrahepatic Cholangiocarcinoma (iCCA) is a deadly disease with rising incidence and few treatment options. Recently, aberrant Notch signaling was reported in iCCA carcinogenesis. Specifically, altered expression and/or activation of the receptors Notch1/2 suggests a role for Notch pathway overactivation during iCCA formation and progression. In this study, we examined the effects of Notch inhibition by γ-secretase inhibitor, LY3039478 in human iCCA cell lines and in an excellent patient derived-xenograft (PDX) model. Expression of several Notch pathway components, including NICD, Hes1, and DLL4, were reduced after GSI treatment. Moreover, LY3039478 inhibits cell migration and invasion while in GSI-treated mice, tumor growth was delayed compared to vehicle and chemotherapy. These results support the notion that Notch inhibition by GSI may reduce in vivo tumorigenesis. In addition, GSI reduces in PDX model VEGFA and MMP13 involved in capillary tube formation and tumor progression. Here, we therefore show a link between the efficacy of Notch inhibition and the tumor microenvironment through LY3039478 that slows tumor progression compared to control mice blocking angiogenesis via MMP13 downregulation.

Publication Title

Crenigacestat, a selective NOTCH1 inhibitor, reduces intrahepatic cholangiocarcinoma progression by blocking VEGFA/DLL4/MMP13 axis.

Sample Metadata Fields

Specimen part, Treatment

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accession-icon GSE34027
EWS TC-71 cell lines: IGF-1R resistant
  • organism-icon Homo sapiens
  • sample-icon 7 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Ewing's Sarcoma cell lines were made resistant to different IGF-1R drugs to investigate mechanisms and pathways modulated by the resistance.

Publication Title

Identification of common and distinctive mechanisms of resistance to different anti-IGF-IR agents in Ewing's sarcoma.

Sample Metadata Fields

Cell line

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accession-icon GSE48027
Host directed activity of Pyrazinamide in Mycobacterium tuberculosis infection
  • organism-icon Mus musculus
  • sample-icon 16 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.0 ST Array (mogene10st)

Description

Pyrazinamide (PZA) is one of the first line antibiotics used for the treatment of tuberculosis (TB). we have used human monocyte and a mouse model of pulmonary TB to investigate whether treatment with PZA, in addition to its known anti-mycobacterial properties, modulate the host immune response during Mycobacterium tuberculosis (Mtb) infection.

Publication Title

Host targeted activity of pyrazinamide in Mycobacterium tuberculosis infection.

Sample Metadata Fields

Specimen part, Treatment, Time

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accession-icon GSE27648
Expression profile of Maize (Zea mays L.) Embryonic Axes During Germination: Regulation of Ribosomal Protein mRNAs.
  • organism-icon Zea mays
  • sample-icon 14 Downloadable Samples
  • Technology Badge Icon Affymetrix Maize Genome Array (maize)

Description

Seed germination is a critical developmental process in plant propagation. Knowledge of the gene expression patterns in this critical process is important in order to understand the main biochemical reactions involved in successful germination, specially for economically relevant plants such as Maize.

Publication Title

Expression profile of maize (Zea mays L.) embryonic axes during germination: translational regulation of ribosomal protein mRNAs.

Sample Metadata Fields

Treatment, Time

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accession-icon GSE8646
The Hay Wells Syndrome-Derived TAp63alphaQ540L Mutant Has Impaired Transcriptional and Cell Growth Regulatory Activity
  • organism-icon Homo sapiens
  • sample-icon 11 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

p63 mutations have been associated with several human hereditary disorders characterized by ectodermal dysplasia such as EEC syndrome, ADULT syndrome and AEC syndrome . The location and functional effects of the mutations that underlie these syndromes reveal a striking genotype-phenotype correlation. Unlike EEC and ADULT that result from missense mutations in the DNA-binding domain of p63, AEC is solely caused by missense mutations in the SAM domain of p63. We report a study on the TAp63a isoform, the first to be expressed during development of the embryonic epithelia, and on its naturally occurring Q540L mutant derived from an AEC patient. To assess the effects of the Q540L mutation, we generated stable cell lines expressing TAp63a wt, DeltaNp63 alpha or the TAp63 alpha-Q540L mutant protein and used them to systematically compare the cell growth regulatory activity of the mutant and wt p63 proteins and to generate, by microarray analysis, a comprehensive profile of differential gene expression. We found that the Q540L substitution impairs the transcriptional activity of TAp63a and causes misregulation of genes involved in the control of cell growth and epidermal differentiation.

Publication Title

The Hay Wells syndrome-derived TAp63alphaQ540L mutant has impaired transcriptional and cell growth regulatory activity.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE25313
Effect of PDE4 inhibition on host gene expression of Mtb-infected mouse lungs.
  • organism-icon Mus musculus
  • sample-icon 47 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.0 ST Array (mogene10st)

Description

Global gene expressions of Mtb-infected mouse lungs were compared between with and without PDE4 inhibitor treatment. A lot of host genes are differentially expressed 21d and 28d post-Mtb infection. PDE4 inhibitor, however, downregulate 10% of genes among those and genes differentially regulated by PDE4 inhibitor are mainly involved immune response.

Publication Title

Phosphodiesterase 4 inhibition reduces innate immunity and improves isoniazid clearance of Mycobacterium tuberculosis in the lungs of infected mice.

Sample Metadata Fields

Specimen part, Disease, Disease stage

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accession-icon SRP064952
Transcriptomics of adult human small bowel grafts
  • organism-icon Homo sapiens
  • sample-icon 24 Downloadable Samples
  • Technology Badge IconIlluminaGenomeAnalyzerIIx

Description

Objective: the objective of this work was to determine different gene expression patterns in small bowel grafts biopsies with “minimal changes” histology that could identify patients with high rejection risk Methods: 24 samples (17 stable and 7 non stable grafts) from 8 adult patients with small bowel transplantation were included for RNA-Sequencing.Total RNA extracted from intestinal biopsies was used with the TruSeq RNA Sample Preparation v2 Kit to construct index-tagged cDNA libraries. Libraries were sequenced on the Genome Analyzer IIx following the standard RNA sequencing protocol with the TruSeq SBS Kit v5. Fastq files containing reads for each library were extracted and demultiplexed using Casava v1.8.2 pipeline. Sequencing adapter contaminations were removed from reads using Cutadapt software v1.6 and the resulting reads were aligned to the reference human genome (Ensembl gene-build GRCh37.75) using TopHat2 v2.0.13. Gene expression values were calculated as counts using HTSeq v0.6.1. Only genes with at least 1 count per million in all samples were considered for statistical analysis. Data were then normalized and differential expression tested using the R Bioconductor package edgeR. We selected all biopsies from 4 of the patients (18 biopsies, 11 stable and 7 non stable) as the discovery set. The other 6 biopsies from 4 patients (all stable) were used as the test set. Differences in the discovery set were tested by generalized linear model analysis,and results were considered significant when the Benjamini-Hochberg adjusted p-value was < 0,05. Results: We obtained 816 differentially expressed genes (DEGs) between stable and non stable biopsies in the discovery set: 369 upregulated and 447 downregulated in the non stable group. The classification and prediction with the Nearest Shrunken Centroids method identified 5 genes (ADH1C, CYP4F2, PDZK1, SLC39A4 and OPTN) from the 816 DEGs that could classify both groups with an error rate of 11% and classified correctly all samples from the test set. These results were confirmed by Supoprted Vector Machine (SVM), bagSVM and Random Forest methods, showing high accuracy, sensitivity and specificity. Conclusions: We identified 5 genes from the DEGs as possible biomarkers to classify patients with normal histology that could be however in a higher risk of rejection. In this way, gene expression assays are powerful tools with high sensitivity that allow more accurate diagnosis. Overall design: The study included 24 samples from 8 adult patients with small bowel transplantation. Samples correspond to RNA extracted from intestinal biopsies obtained at different post-transplantation time. All biopsies have an histological diagnosis of "minimal changes" and they were classified in two groups according their immunological stability (stable and non stable). Stable group comprised biopsies of patients that never rejected and biopsies obtained at least 15 days after rejection if no other rejection episode occurred in at least the next six months. Non stable group included biopsies obtained between rejection episodes (separated less than six months) and also those biopsies collected within the 15 days before the first rejection episode.

Publication Title

5-gene differential expression predicts stability of human intestinal allografts.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE2852
Ochratoxin A study on rat liver and kidney gene expression
  • organism-icon Rattus norvegicus
  • sample-icon 60 Downloadable Samples
  • Technology Badge Icon Affymetrix Rat Genome U34 Array (rgu34a), Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)

Description

Ochratoxin A gene expression profiling in liver and kidney, with time points of exposure from 7 days to 12 motnhs

Publication Title

A toxicogenomics approach to identify new plausible epigenetic mechanisms of ochratoxin a carcinogenicity in rat.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE31415
Comparison of WAT CD34+ vs LAF CD34+
  • organism-icon Homo sapiens
  • sample-icon 4 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Gene 1.0 ST Array (hugene10st)

Description

A catalytic role has been proposed in neoplastic angiogenesis and cancer progression for bone marrow-derived endothelial progenitor cells (EPCs). However, in preclinical and clinical studies the quantitative role of marrow-derived EPCs in cancer vascularization was found to be extremely variable. Adipose tissue represents an attractive source of autologous adult stem cells due to its abundance and surgical accessibility. CD34+cells from Lipotransfer aspirates (LAs) of patients undergoing breast reconstruction after breast cancer surgery were compared with CD34+ cells from Leucapheresis of normal subjects.

Publication Title

The white adipose tissue used in lipotransfer procedures is a rich reservoir of CD34+ progenitors able to promote cancer progression.

Sample Metadata Fields

Sex

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accession-icon GSE59201
Gene expression changes during retinal development and rod specification.
  • organism-icon Mus musculus
  • sample-icon 20 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)

Description

Photoreceptor disorders are collectively known as retinal degeneration (RD), and include retinitis pigmentosa (RP), cone-rod dystrophy and age related macular degeneration (AMD). These disorders are largely genetic in origin; individual mutations in any one of >200 genes cause RD, making mutation specific therapies prohibitively expensive. A better treatment plan, particularly for late stage disease, may involve stem cell transplants into the photoreceptor or ganglion cell layers of the retina. Stem cells from young mouse retinas can be transplanted, and can form photoreceptors in adult retinas. These cells can be grown in tissue culture, but can no longer form photoreceptors. We have used microarrays to investigate differences in gene expression between cultured retinal progenitor cells (RPCs) that have lost photoreceptor potential, postnatal day 1 (pn1) retinas and the postnatal day 5 (pn5) retinas that contain transplantable photoreceptors. We have also compared FACS sorted Rho-eGFP expressing rod photoreceptors from pn5 retinas with Rho-eGFP negative cells from the same retinas. We have identified over 300 genes upregulated in rod photoreceptor development in multiple comparisons, 37 of which have been previously identified as causative of retinal disease when mutated. It is anticipated that this research should bring us closer to growing photoreceptors in culture and therefore better treatments for RD. This dataset is also a resource for those seeking to identify novel retinopathy genes in RD patients.

Publication Title

Gene expression changes during retinal development and rod specification.

Sample Metadata Fields

No sample metadata fields

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refine.bio is a repository of uniformly processed and normalized, ready-to-use transcriptome data from publicly available sources. refine.bio is a project of the Childhood Cancer Data Lab (CCDL)

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Cite refine.bio

Casey S. Greene, Dongbo Hu, Richard W. W. Jones, Stephanie Liu, David S. Mejia, Rob Patro, Stephen R. Piccolo, Ariel Rodriguez Romero, Hirak Sarkar, Candace L. Savonen, Jaclyn N. Taroni, William E. Vauclain, Deepashree Venkatesh Prasad, Kurt G. Wheeler. refine.bio: a resource of uniformly processed publicly available gene expression datasets.
URL: https://www.refine.bio

Note that the contributor list is in alphabetical order as we prepare a manuscript for submission.

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