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GSE54054
Mus musculus
20 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Hepatocellular carcinoma (HCC) is a deadly disease, often unnoticed till the late stages, where treatment options become limited. Thus, there is a critical need to identify early biomarkers for detection of the developing HCC, as well as molecular pathways that would be amenable to therapeutic intervention. While efforts using human serum and tissues from late stage patients have been undertaken, progress has been limited. We have therefore explored the possibility of utilizing established mouse models for the discovery of biomarkers, as well as to understand in a systematic manner the molecular pathways that are progressively deregulated by the various etiological factors in contributing to HCC formation. As an initial effort, we have used the Hepatitis B surface antigen (HBsAg) transgenic mice as a hepatitis model, which have been exposed to aflatoxin B1 (AFB1). In this report, we present the initial findings from a extensive longitudinal study, which confirms the synergistic effect of both these etiological factors, with a gender bias towards male mice. Tumors from the mouse models were validated both histologically as well as by molecular transcriptome analysis by comparison with human HCCs. In addition, using these models, we have identified carnitine as a novel biomarker for HCC development, which was again validated using human HCC samples. Conclusion: This study therefore highlights the utility of these mouse models in identifying biomarkers for detection of human HCCs, as well as for the systematic analysis of molecular pathways that are affected by various etiological agents during the progression of HCC from an untransformed hepatocyte, which could provide novel options for targeted therapy.
Publication Title
Molecular characterization of hepatocarcinogenesis using mouse models.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
A phase I trial of a SRC kinase Inhibitor, dasatinib, in combination with paclitaxel and carboplatin in patients with advanced or recurrent ovarian cancer. Background: We conducted a phase I study of dasatinib, an oral SRC tyrosine kinase inhibitor, in combination with paclitaxel and carboplatin in advanced and recurrent epithelial ovarian cancer (EOC). Methods: The primary objective was to determine the maximum tolerated dose (MTD). Secondary objectives included toxicity, response rate (RR), pharmacokinetics and pharmacodynamics. Based on the 3+3 design, cohorts of 3-6 pts received paclitaxel 175 mg/m2 and carboplatin AUC 6 every three weeks with escalating doses of dasatinib (100, 120, 150 mg daily), followed by an 8 patient expansion cohort. Results: Twenty patients were enrolled between 06/07 and 12/09. The median age was 61 yrs (42-82) with a median of 2 prior regimens (0-6), and 71% had platinum-sensitive disease. There were 3-6 pts in each cohort, and 8 in the expansion cohort. Pharmacokinetics were observed over the first 2 cycles of therapy. One DLT was observed in the 100 mg dasatinib cohort (grade 3 myalgia. Other toxicities in all cycles included neutropenia (95% grade 3-4), thrombocytopenia (35% grade 3-4), and fatigue (10% grade 3). The RR was 45% (complete responses, 3/18(17%); partial responses, 5/18(28%)) and 56% (10/18) had stable disease. The PFS6-month actuarial estimate was 86%. The median PFS and OS were 7.8 and 16.2 months, respectively. Conclusions: Due to the high incidence of myelosuppression with subsequent cycles the recommended phase II dose is 150 mg daily of dasatinib in combination with paclitaxel and carboplatin. The combination was safe with evidence of clinical activity in advanced EOC.
Publication Title
A phase I trial of dasatinib, an SRC-family kinase inhibitor, in combination with paclitaxel and carboplatin in patients with advanced or recurrent ovarian cancer.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Cell tracking is enabled by incubating ex vivo cells with commercially/clinically available MRI particulate label, such as ferucarbotran. However, the uptake by non-phagocytic cells, such as mesenchymal stem cell (MSC) is poor, and the detection by MRI is impeded. MGIO is a new label that is efficiently taken up by MSC. The proliferation and differentiation capacity of labelled cells are usually assessed to determine cytotoxicity. In this study, we compared the global gene expression profiles of mock-labelled, ferucarbotran-labelled and MGIO-labelled fetal MSC.
Publication Title
Microgel iron oxide nanoparticles for tracking human fetal mesenchymal stem cells through magnetic resonance imaging.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
MicroRNA-10b pleiotropically regulates invasion, angiogenicity and apoptosis of tumor cells resembling mesenchymal subtype of glioblastoma multiforme.
Sample Metadata Fields
Specimen part, Cell line
View Samples SRP128859- Homo sapiens
- 9 Downloadable Samples
Illumina HiSeq 4000
Description
Downregulation of EZH2 Leads to Cellular Senescence with Features of SASP Overall design: Cells were infected with a lentivirus vector expressing shRNA against EZH2 and harvested at 4 and 8 days after infection. Total RNA was harvested from cells using Trizol reagent (Invitrogen) and further purified using the Purelink RNA Mini kit (Invitrogen) with DNase I digestion. RNA library preparation with polyA selection and Illumina HiSeq 2x150bp sequencing was performed by GeneWiz Inc. Paired-end reads were quality trimmed using Trim galore v0.4.0 and subsequently aligned to the human reference genome, hg19, using HISAT2 v2.1.0. Reads mapping to annotated genes were quantified using featureCounts (Liao et al., 2014). Differential gene expression was determined using DESeq2 v1.12.4 (Love et al., 2014) and significance was defined as FDR-corrected p-values of <0.05. The log2 fold change for each gene was used to rank the list of genes for GSEAPreranked analysis (Subramanian et al., 2005). FPKM values were calculated using DESeq2 and Z-scores were generated from FPKMs
Publication Title
Regulation of Cellular Senescence by Polycomb Chromatin Modifiers through Distinct DNA Damage- and Histone Methylation-Dependent Pathways.
Sample Metadata Fields
Subject, Time
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
An experimental lung metastasis assay was used to derive an invasive subline of U87 that is metastatic in mice.
Publication Title
MicroRNA-10b pleiotropically regulates invasion, angiogenicity and apoptosis of tumor cells resembling mesenchymal subtype of glioblastoma multiforme.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 5 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
MicroRNA-10b may target numerous genes in gliomagenesis. The target genes of miR-10b may differ according to the cellular context.
Publication Title
MicroRNA-10b pleiotropically regulates invasion, angiogenicity and apoptosis of tumor cells resembling mesenchymal subtype of glioblastoma multiforme.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
Chromosomal translocation t(8;21) (q22;q22) leading to generation of oncogenic RUNX1-RUNX1T1 (AML1-ETO) fusion is a cytogenetic abnormality observed in about 10% of acute myelogenous leukemia (AML). To uncover somatic mutations that cooperate with t(8;21)-driven leukemia, we performed targeted and whole exome sequencing of newly-diagnosed and relapsed AML samples. We identified high frequency of truncating alterations in ASXL2 along with recurrent mutations of KIT, TET2, MGA, FLT3, and DHX15 in this subtype of AML. To investigate in-depth the role of ASXL2 in normal and malignant hematopoiesis, we utilized a mouse model of ASXL2 deficiency. Loss of ASXL2 caused progressive hematopoietic defects characterized by myeloid cell expansion, splenomegaly, extramedullary hematopoiesis and poor reconstitution ability in transplantation models. A parallel analysis of young and >1-year old Asxl2-deficient mice revealed age-dependent changes in the hematopoietic compartment leading to perturbations affecting not only myeloid and erythroid differentiation but also maturation of lymphoid cells. Our studies also suggest that expression of truncated ASXL2 protein confers proliferative advantage to mouse myeloid progenitors. Overall, these findings establish a critical role of ASXL2 in maintaining steady state hematopoiesis and provide insights into how its loss/mutation primes leukemic growth of myeloid cells. Overall design: Bone marrow derived LSK cells from young (8-12 weeks old) and >1-year old Asxl2 WT and knockout mice were analyzed for gene expression changes.
Publication Title
ASXL2 regulates hematopoiesis in mice and its deficiency promotes myeloid expansion.
Sample Metadata Fields
Subject
View Samples- Rattus norvegicus
- 18 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
A doxycyline-inducible INS-1 insulinoma cell line expressing proinsulin (C96Y)-GFP was engineered. Addition of doxycyline causes the production of the proinsulin (C96Y)-GFP, which is retained in the endoplasmic reticulum. This study analyzes the gene expression changes that occur after doxycyline-induced expression of proinsulin (C96Y)-GFP for 24h, 48h and 5 days. Expression changes were compared between control un-induced cells and cells treated with doxycyline. Three replicates (experiments) were performed for each time point.
Publication Title
Endoplasmic reticulum stress response in an INS-1 pancreatic beta-cell line with inducible expression of a folding-deficient proinsulin.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Regulation of constitutive and alternative splicing by PRMT5 reveals a role for Mdm4 pre-mRNA in sensing defects in the spliceosomal machinery.
Sample Metadata Fields
Specimen part, Treatment
View Samples