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GSE58401
Homo sapiens
129 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Translational validation of personalized treatment strategy based on genetic characteristics of glioblastoma.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 104 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Glioblastoma (GBM) heterogeneity in the genomic and phenotypic properties has potentiated personalized approach against specific therapeutic targets of each GBM patient. The Cancer Genome Atlas (TCGA) Research Network has been established the comprehensive genomic abnormalities of GBM, which sub-classified GBMs into 4 different molecular subtypes. The molecular subtypes could be utilized to develop personalized treatment strategy for each subtype. We applied a classifying method, NTP (Nearest Template Prediction) method to determine molecular subtype of each GBM patient and corresponding orthotopic xenograft animal model. The models were derived from GBM cells dissociated from patient's surgical sample. Specific drug candidates for each subtype were selected using an integrated pharmacological network database (PharmDB), which link drugs with subtype specific genes. Treatment effects of the drug candidates were determined by in vitro limiting dilution assay using patient-derived GBM cells primarily cultured from orthotopic xenograft tumors. The consistent identification of molecular subtype by the NTP method was validated using TCGA database. When subtypes were determined by the NTP method, orthotopic xenograft animal models faithfully maintained the molecular subtypes of parental tumors. Subtype specific drugs not only showed significant inhibition effects on the in vitro clonogenicity of patient-derived GBM cells but also synergistically reversed temozolomide resistance of MGMT-unmethylated patient-derived GBM cells. However, inhibitory effects on the clonogenicity were not totally subtype-specific. Personalized treatment approach based on genetic characteristics of each GBM could make better treatment outcomes of GBMs, although more sophisticated classifying techniques and subtype specific drugs need to be further elucidated.
Publication Title
Translational validation of personalized treatment strategy based on genetic characteristics of glioblastoma.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 25 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Glioblastoma (GBM) heterogeneity in the genomic and phenotypic properties has potentiated personalized approach against specific therapeutic targets of each GBM patient. The Cancer Genome Atlas (TCGA) Research Network has been established the comprehensive genomic abnormalities of GBM, which sub-classified GBMs into 4 different molecular subtypes. The molecular subtypes could be utilized to develop personalized treatment strategy for each subtype. We applied a classifying method, NTP (Nearest Template Prediction) method to determine molecular subtype of each GBM patient and corresponding orthotopic xenograft animal model. The models were derived from GBM cells dissociated from patient's surgical sample. Specific drug candidates for each subtype were selected using an integrated pharmacological network database (PharmDB), which link drugs with subtype specific genes. Treatment effects of the drug candidates were determined by in vitro limiting dilution assay using patient-derived GBM cells primarily cultured from orthotopic xenograft tumors. The consistent identification of molecular subtype by the NTP method was validated using TCGA database. When subtypes were determined by the NTP method, orthotopic xenograft animal models faithfully maintained the molecular subtypes of parental tumors. Subtype specific drugs not only showed significant inhibition effects on the in vitro clonogenicity of patient-derived GBM cells but also synergistically reversed temozolomide resistance of MGMT-unmethylated patient-derived GBM cells. However, inhibitory effects on the clonogenicity were not totally subtype-specific. Personalized treatment approach based on genetic characteristics of each GBM could make better treatment outcomes of GBMs, although more sophisticated classifying techniques and subtype specific drugs need to be further elucidated.
Publication Title
Translational validation of personalized treatment strategy based on genetic characteristics of glioblastoma.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 63 Downloadable Samples
- Illumina human-6 v2.0 expression beadchip
Description
Cholangiocarcinoma (CC) is an aggressive tumor that shows a poor survival rate even after resection. The present study aimed at identification of the genome-wide expressed genes related to CC oncogenesis and its sarcomatous transdifferentiation using DNA microarray technology. The differentially expressed genes in 9 cholangiocarcinoma cell lines (Choi.CK, Cho.CK, J.CK, S.CK, CK.L1, CK.L2, CK.P1, CK.P2 and CK.Y1) were analyzed in comparison with 4 kinds of cultured biliary epithelial cells (ND.1, ND.2, ND.3 and ND.4) using the Illumina Human-6 v2 BeadChip (48 K). Unsupervised hierachical clustering analysis perfectively classified the 13 cell samples into two groups, normal biliary epithelial (N) and immortalized biliary epithelial cells and CC (T) cells. We identified 120 commonly upregulated ( > 2.5 fold) genes and 340 commonly downregulated ( < 0.4-fold) genes in the two groups. Hierachical clustering analysis of sarcomatoid CC cells (S.CK) revealed 316 differentially upregulated genes (> 4-fold) and 335 downregulated genes (< 0.25-fold).) compared with 3 CC cell lines (Choi.CK, Cho.CK, and J.CK). In conclusion, these data will contribute to better understand the molecular mechanisms of oncogenesis and transdifferentiation in CC and provide the molecular targets for CC diagnosis and therapy.
Publication Title
Genome-wide expression patterns associated with oncogenesis and sarcomatous transdifferentation of cholangiocarcinoma.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 28 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st), Agilent-014693 Human Genome CGH Microarray 244A (Feature number version)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Patient-specific orthotopic glioblastoma xenograft models recapitulate the histopathology and biology of human glioblastomas in situ.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 28 Downloadable Samples
- Agilent-014693 Human Genome CGH Microarray 244A (Feature number version), Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Frequent discrepancies between preclinical and clinical results of anti-cancer agents demand a reliable translational platform that can precisely recapitulate the biology of human cancers. Another critical unmet need is the ability to predict therapeutic responses for individual patients. Toward this goal, we have established a library of orthotopic glioblastoma (GBM) xenograft models using surgical samples of GBM patients. These patient-specific GBM xenograft tumors recapitulate histopathological properties and maintain genomic characteristics of parental GBMs in situ. Furthermore, in vivo irradiation, chemotherapy, and targeted therapy of these xenograft tumors mimic the treatment response of parental GBMs. We also found that establishment of orthotopic xenograft models portends poor prognosis of GBM patients and identified the gene signatures and pathways signatures associated with the clinical aggressiveness of GBMs. Together, the patient-specific orthotopic GBM xenograft library represent the preclinically and clinically valuable patient tumors phenocopy that represents molecular and functional heterogeneity of GBMs.
Publication Title
Patient-specific orthotopic glioblastoma xenograft models recapitulate the histopathology and biology of human glioblastomas in situ.
Sample Metadata Fields
Sex, Age, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
IlluminaHiSeq2500
Description
SAMHD1 restricts HIV-1 replication in dendritic and other myeloid cells. SAMHD1 has been shown to possess a dGTP-dependent dNTP triphosphatase (dNTPase) activity and is proposed to inhibit HIV-1 replication by depleting the intracellular dNTP pool. Arguing against a role for SAMHD1 dNTPase in HIV-1 restriction, the phosphorylation of SAMHD1 regulates the restriction activity toward HIV-1 without affecting its ability to decrease cellular dNTP levels. Here, we show that SAMHD1 is a phospho-regulated RNase and that the RNase function is required for HIV-1 restriction. Mutation of the SAMHD1 D137 residue in the allosteric site (SAMHD1D137N) abolishes dNTPase activity but has no effect on RNase activity. This dNTPase-defective SAMHD1D137N mutant is able to restrict HIV-1 infection to nearly the same extent as wild-type SAMHD1. SAMHD1 associates with and degrades the HIV-1 genomic RNA during the early phases of infection. SAMHD1 silencing in macrophages and CD4+ T cells from healthy donors increases HIV-1 RNA stability, thus rendering the cells permissive for HIV-1 infection. Furthermore, the phosphorylation of SAMHD1 at position T592 abolishes the RNase activity toward HIV-1 RNA, and consequently the ability of SAMHD1 to restrict HIV-1 infection, uncovering the phosphorylation of SAMHD1 T592 as a negative regulatory mechanism of RNase activity. Together, our results demonstrate that SAMHD1 is an essential RNase that prevents HIV-1 infection by directly degrading HIV-1 genomic RNA in a phosphorylation-regulated manner. The unique property of SAMHD1 that cleaves HIV-1 genomic RNA with no sequence preferences could be exploited to develop a new class of intervention for error-prone retroviruses. Overall design: Ribosomal RNA-depleted total RNA profiles of mock, SAMHD1 wild type and mutants infected with HIV-1 were examined at the time of 0, 1, 3 h by Illumina Hiseq2500.
Publication Title
The ribonuclease activity of SAMHD1 is required for HIV-1 restriction.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
GPCR19 pathway has been implicated in regulating various inflammation. However, the exact mechanism of immune regulation by GPCR19 pathway has not been elucidated in detail.
Publication Title
Taurodeoxycholate Increases the Number of Myeloid-Derived Suppressor Cells That Ameliorate Sepsis in Mice.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
To gain insights into the mechanism responsible for the protumorigenic actions of NRG we performed gene expression analyses of MCF7 cells treated with soluble NRG for 3, 6, 12 and 24 hours.
Publication Title
Breast cancer dissemination promoted by a neuregulin-collagenase 3 signalling node.
Sample Metadata Fields
Age, Specimen part, Disease, Cell line, Treatment, Time
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
Background: Substantial progress has been made in the identification of sequence elements that control mRNA splicing and the genetic variants in these elements that alter mRNA splicing (referred to as splicing quantitative trait loci -- sQTLs). Genetic variants that affect mRNA splicing in trans are harder to identify because their effects can be more subtle and diffuse, and the variants are not co-located with their targets. We carried out a transcriptome-wide analysis of the effects of a mutation in a ubiquitous splicing factor that causes retinitis pigmentosa (RP) on mRNA splicing, using exon microarrays.
Publication Title
A mutation in a splicing factor that causes retinitis pigmentosa has a transcriptome-wide effect on mRNA splicing.
Sample Metadata Fields
Specimen part
View Samples