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SRP045898
Homo sapiens
6 Downloadable Samples
IlluminaHiSeq2000
Description
Anti-angiogenic therapy is commonly used for the treatment of CRC. Although patients derive some clinical benefit, treatment resistance inevitably occurs. The MET signaling pathway has been proposed to be a major contributor of resistance to anti-angiogenic therapy. MET is upregulated in response to VEGF pathway inhibition and plays an essential role in tumorigenesis and progression of tumors. In this study we set out to determine the efficacy of cabozantinib in a preclinical CRC PDTX model. We demonstrate potent inhibitory effects on tumor growth in 80% of tumors treated. The greatest antitumor effects were observed in tumors that possess a mutation in the PIK3CA gene. The underlying antitumor mechanisms of cabozantinib consisted of inhibition of angiogenesis and Akt activation and significantly decreased expression of genes involved in the PI3K pathway. These findings support further evaluation of cabozantinib in patients with CRC. PIK3CA mutation as a predictive biomarker of sensitivity is intriguing and warrants further elucidation. A clinical trial of cabozantinib in refractory metastatic CRC is being activated. Overall design: CRC PDTX Model treated with cabozantinib
Publication Title
Potent antitumor activity of cabozantinib, a c-MET and VEGFR2 inhibitor, in a colorectal cancer patient-derived tumor explant model.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 6 Downloadable Samples
Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Determination of the mechanism by which fibrinogen, a central blood coagulation protein, regulates OPC functions and remyelination in the CNS.
Publication Title
Fibrinogen Activates BMP Signaling in Oligodendrocyte Progenitor Cells and Inhibits Remyelination after Vascular Damage.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 6 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Determination of the mechanism by which fibrinogen, a central blood coagulation protein, regulates OPC functions and remyelination in the CNS.
Publication Title
Fibrinogen Activates BMP Signaling in Oligodendrocyte Progenitor Cells and Inhibits Remyelination after Vascular Damage.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 1 Downloadable Sample
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Fibrinogen Activates BMP Signaling in Oligodendrocyte Progenitor Cells and Inhibits Remyelination after Vascular Damage.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 72 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
A preliminary understanding of the phenotypic effect of copy number variation (CNV) of DNA segments is emerging. These rearrangements were demonstrated to influence, in a somewhat dose-dependent manner, the expression of genes mapping within. They were shown to also affect the expression of genes located on their flanks, sometimes at great distance. Here, we show by monitoring these effects at multiple life stages, that these controls over expression are effective throughout mouse development. Similarly, we observe that the more specific spatial expression patterns of CNV genes are maintained throughout life. However, we find that some brain-expressed genes appear to be under compensatory loops only at specific time-points, indicating that the influence of CNVs on these genes is modulated through development. We also observe that CNV genes are significantly enriched upon transcripts that show variable time-course of expression in different strains. Thus modifying the number of copy of a gene not only potentially alters its expression level, but possibly also its time of expression.
Publication Title
Copy number variation modifies expression time courses.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina HiSeq 1500
Description
Inhibition of ZNF768 function was achieved by conditional over expression expression of the C-terminal zinc finger of ZNF768 for 12h. For preparation of total RNA cells were resuspended in TRIzol reagent (Life Technologies) at 0.9Mio/ml and snap-frozen. After thawing RNA was extracted from 0.4ml of TriZol lysate using the direct-zol RNA Miniprep (Zymo Research, Irvine CA, USA) as described in the manufacturer's protocol. RNA was assessed for purity by UV-vis spectrometry (Nanodrop) and for integrity by Bioanalyzer (Agilent Bioanalyzer 2100, Agilent, Santa Clara USA)). RNA was of high purity (abs. 260/280 >1.9, abs 269/239>2.1) and integrity (Bioanalyzer RIN>9 ) and thus used for further processing. For production of RNA-seq libraries total RNA was DNAse treated (dsDNAse, Fermentas) and 100 ng of this RNA was processed with a strand-specific protocol (RNA-seq complete kit, NuGEN, San Carlos, USA). In brief the RNA was reverse transcribed to cDNA with a reduced set of hexamer primers, avoiding excessive representation of rRNA in the cDNA. Second strand cDNA synthesis was done in presence of dUTP. After ultrasonic fragmentation of the cDNA and end repair, Illumina-compatible adapter were ligated. Adapters contained uracil in one strand, allowing complete digestion of the second-strand derived DNA. After strand selection the libraries were amplified, assessed for correct insert size on the Agilent Bioanalyser and diluted to 10nM. Barcoded libraries were mixed in equimolar amounts and sequenced on an Illumina HiSeq1500 in single-read mode with a read length of 100 b. Overall design: ZNF768-deltaN
Publication Title
MIR sequences recruit zinc finger protein ZNF768 to expressed genes.
Sample Metadata Fields
Treatment, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
A humanized in vivo APL model has been established utilizing the retroviral transduction of PML-RARA into human CD34+ hematopoietic cells and the transplantation of these cells into immunodeficient mice. The resultant leukemia recapitulated human APL phenotypically, and was clustered in the same category as human APL samples in the gene expression analysis.
Publication Title
Establishment of a humanized APL model via the transplantation of PML-RARA-transduced human common myeloid progenitors into immunodeficient mice.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 66 Downloadable Samples
Illumina human-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Molecular signatures of cardiac defects in Down syndrome lymphoblastoid cell lines suggest altered ciliome and Hedgehog pathways.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 43 Downloadable Samples
- Illumina human-6 v2.0 expression beadchip
Description
Molecular Signatures of cardiac defects in Down syndrome lymphoblastoid cell lines. In this study, we want to identify genes and pathways specifically dysregulated in atrioventricular septal defect and /or atrial septal defect + ventricular septal defect in case of trisomy 21.
Publication Title
Molecular signatures of cardiac defects in Down syndrome lymphoblastoid cell lines suggest altered ciliome and Hedgehog pathways.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 23 Downloadable Samples
- Illumina human-6 v2.0 expression beadchip
Description
Molecular consequences of trisomy in lymphoblastoid cell lines from patients with Down syndrome. This project analyses differentially expressed genes between humans with trisomy 21 and humans without trisomy 21.
Publication Title
Molecular signatures of cardiac defects in Down syndrome lymphoblastoid cell lines suggest altered ciliome and Hedgehog pathways.
Sample Metadata Fields
Sex, Specimen part
View Samples