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SRP149159
Mus musculus
52 Downloadable Samples
Illumina HiSeq 2500
Description
Large numbers of ribonucleotides are incorporated into the eukaryotic nuclear genome during S-phase due to imperfect discrimination against ribonucleoside triphosphates by the replicative DNA polymerases. Ribonucleotides, by far the most common DNA lesion in replicating cells, destabilize the DNA, and an evolutionarily conserved DNA repair machinery, ribonucleotide excision repair (RER), ensures ribonucleotide removal. Complete lack of RER is embryonically lethal. Partial loss-of-function mutations in the genes encoding subunits of RNase H2, the enzyme essential for initiation of RER, cause the SLE-related type I interferonopathy Aicardi-Goutières syndrome. Here we establish that selective inactivation of RER in mouse epidermis results in spontaneous DNA damage, epidermal hyperproliferation associated with loss of hair follicle stem cells and hair follicle function. The animals develop keratinocyte intraepithelial neoplasia and invasive squamous cell carcinoma with complete penetrance, despite potent type I interferon production and skin inflammation. Compromised RER-mediated genome maintenance might represent an important tumor-promoting principle in human cancer. Overall design: CD45+ CD49f- cells were were isolated from skin cell suspensions by FACS. Total RNA was isolated using the RNeasy Micro Kit+ (Qiagen). mRNA libraries were prepared using a SMART protocol and subjected to deep sequencing on an Illumina®HiSeq 2500.
Publication Title
Ribonucleotide Excision Repair Is Essential to Prevent Squamous Cell Carcinoma of the Skin.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina HiSeq 2500
Description
Large numbers of ribonucleotides are incorporated into the eukaryotic nuclear genome during S-phase due to imperfect discrimination against ribonucleoside triphosphates by the replicative DNA polymerases. Ribonucleotides, by far the most common DNA lesion in replicating cells, destabilize the DNA, and an evolutionarily conserved DNA repair machinery, ribonucleotide excision repair (RER), ensures ribonucleotide removal. Complete lack of RER is embryonically lethal. Partial loss-of-function mutations in the genes encoding subunits of RNase H2, the enzyme essential for initiation of RER, cause the SLE-related type I interferonopathy Aicardi-Goutières syndrome. Here we establish that selective inactivation of RER in mouse epidermis results in spontaneous DNA damage, epidermal hyperproliferation associated with loss of hair follicle stem cells and hair follicle function. The animals develop keratinocyte intraepithelial neoplasia and invasive squamous cell carcinoma with complete penetrance, despite potent type I interferon production and skin inflammation. Compromised RER-mediated genome maintenance might represent an important tumor-promoting principle in human cancer. Overall design: Keratinocytes (CD49f+) cells were isolated from skin cell suspensions by FACS. Total RNA was isolated using the RNeasy Mini Kit+ (Qiagen). mRNA libraries were prepared and subjected to deep sequencing on an Illumina®HiSeq.
Publication Title
Ribonucleotide Excision Repair Is Essential to Prevent Squamous Cell Carcinoma of the Skin.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 80 Downloadable Samples
Illumina HumanWG-6 v3.0 expression beadchip
Description
Emerging biomarkers based on medical images and molecular characterization of tumor biopsies open up for combining the two disciplines and exploiting their synergy in treatment planning. We compared pretreatment classification of cervical cancer patients by two previously validated imaging- and gene-based hypoxia biomarkers, evaluated the influence of intratumor heterogeneity, and investigated the benefit of combining them in prediction of treatment failure. The imaging-based biomarker was hypoxic fraction, determined from diagnostic dynamic contrast enhanced (DCE)-MR images. The gene-based biomarker was a hypoxia gene expression signature determined from tumor biopsies. Paired data were available for 118 patients. Intratumor heterogeneity was assessed by variance analysis of MR images and multiple biopsies from the same tumor. The two biomarkers were combined using a dimension-reduction procedure. The biomarkers classified 75% of the tumors with the same hypoxia status. Both intratumor heterogeneity and distribution pattern of hypoxia from imaging were unrelated to inconsistent classification by the two biomarkers, and the hypoxia status of the slice covering the biopsy region was representative of the whole tumor. Hypoxia by genes was independent on tumor cell fraction and showed minor heterogeneity across multiple biopsies in 9 tumors. This suggested that the two biomarkers could contain complementary biological information. Combination of the biomarkers into a composite score led to improved prediction of treatment failure (HR:7.3) compared to imaging (HR:3.8) and genes (HR:3.0) and prognostic impact in multivariate analysis with clinical variables. In conclusion, combining imaging- and gene-based biomarkers enables more precise and informative assessment of hypoxia-related treatment resistance in cervical cancer, independent of intratumor heterogeneity.
Publication Title
Combining imaging- and gene-based hypoxia biomarkers in cervical cancer improves prediction of chemoradiotherapy failure independent of intratumour heterogeneity.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 18 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip
Description
Microarray analysis reveals up-regulation of retinoic acid and hepatocyte growth factor related signaling pathways by pro-insulin C-peptide in kidney proximal tubular cells: Antagonism of the pro-fibrotic effects of TGF-b1
Publication Title
Proinsulin C-peptide antagonizes the profibrotic effects of TGF-beta1 via up-regulation of retinoic acid and HGF-related signaling pathways.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Analysis of estrogen receptor (ER)-positive MCF7 cell total RNA expression and polysome-assiciated RNA expression following treatment with estradiol (E2) and vehicle (etoh).
Publication Title
Estrogen coordinates translation and transcription, revealing a role for NRSF in human breast cancer cells.
Sample Metadata Fields
Cell line
View Samples- Caenorhabditis elegans
- 123 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
This series of samples comprises multiple early embryonic time courses for C. elegans. Time courses consisting of 10 time points each for 4 different genotypes are included: wild-type (strain N2 grown on E. coli strain OP50), pie-1(zu154) (progeny of homozygous mutant mothers [Unc] of strain JJ532 grown on E. coli strain OP50), pie-1(zu154);pal-1(RNAi) (progeny of homozygous mutant mothers [Unc] of strain JJ532 grown on E. coli strain HT115 expressing pal-1 hairpin RNA), and mex-3(zu155);skn-1(RNAi) (progeny of homozygous mutant mothers [Dpy] of strain JJ518 grown on E. coli strain HT115 expressing skn-1 hairpin RNA). Embryos were manually staged by morphology at the 4-cell stage and allowed to develop in water for defined amounts of time at 22 degrees C. RNA was amplified as described (Baugh et al. Development, 2003; Baugh et al. Nucleic Acids Research, 2001). This series of samples comprises all replicate data reported by Baugh et al. (Development, 2005).
Publication Title
The homeodomain protein PAL-1 specifies a lineage-specific regulatory network in the C. elegans embryo.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 20 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Tumor hypoxia levels range from mild to severe and have different biological and therapeutical consequences, but are not easily assessable in patients. We present a method based on diagnostic dynamic contrast enhanced (DCE) magnetic resonance imaging (MRI) that visualizes a continuous range of hypoxia levels in tumors of cervical cancer patients. Hypoxia images were generated using an established approach based on pixel-wise combination of the DCE-MRI parameters e and Ktrans, reflecting oxygen consumption and supply, respectively. An algorithm to retrieve hypoxia levels from the images was developed and validated in 28 xenograft tumors, by comparing the MRI-defined levels with hypoxia levels derived from pimonidazole stained histological sections. We further established an indicator of hypoxia levels in patient tumors based on expression of nine hypoxia responsive genes. A strong correlation was found between these indicator values and the MRI-defined hypoxia levels in 63 patients. Chemoradiotherapy outcome of 74 patients was most strongly predicted by moderate hypoxia levels, whereas more severe or milder levels were less predictive. By combining gene expression profiles and MRI-defined hypoxia levels in cancer hallmark analysis, we identified a distribution of levels associated with each hallmark; oxidative phosphorylation and G2/M checkpoint were associated with moderate hypoxia, and epithelial-to-mesenchymal transition and inflammatory responses with significantly more severe levels. At the mildest levels, interferon response hallmarks, together with stabilization of HIF1A protein by immunohistochemistry, appearred significant. Thus, our method visualizes the distribution of hypoxia levels within patient tumors and has potential to distinguish levels of different prognostic and biological significance.
Publication Title
MRI Distinguishes Tumor Hypoxia Levels of Different Prognostic and Biological Significance in Cervical Cancer.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 29 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Interacting chemokine signals regulate dendritic cells in acute brain injury.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We inflicted TBI to wildetype (wt) mice in order to establish whether the anti-inflammatory agent cyclophosphamide can be used therapeutically.
Publication Title
Interacting chemokine signals regulate dendritic cells in acute brain injury.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We inflicted TBI to chemokine-deficient mouse lines in order to establish involvement of various signalling pathways that may be addressed therapeutically.
Publication Title
Interacting chemokine signals regulate dendritic cells in acute brain injury.
Sample Metadata Fields
Sex, Specimen part
View Samples