TF1a AML cell line was selected for in vitro modelling of dormancy in AML. TF1-a were subjected to AML-niche-mimicking in vitro conditioning by culture with TGFB1 and the mTOR inhibitor rapamycin. Also TF1a cells were in vitro cultured with prolonged sublethal doses of Etoposide.
A molecular signature of dormancy in CD34<sup>+</sup>CD38<sup>-</sup> acute myeloid leukaemia cells.
Specimen part
View SamplesExperiment: Establishment of expression profiles in a brain metastasis from a PTC (RNA processing and hybridization to Affymetrix microarray done twice to yield a technical replicate), in non-brain metastatic, stage III and IV PTCs, and primary brain tumors. Biostatistics analysis identified genes and biofunctions related to the brain metastatic PTC.
Microarray expression profiling identifies genes, including cytokines, and biofunctions, as diapedesis, associated with a brain metastasis from a papillary thyroid carcinoma.
Sex, Disease stage
View SamplesExperiment: Establishment of expression profiles in HT, PTC with HT, PTC without HT, and mPTC in comparison to TN samples. TN samples were downloaded as CEL files from the repository of the microarray vendor. Biostatistical analysis focussed in first instance on identifying genes and biofunctions related to HT and PTC with HT.
Genetic relationship between Hashimoto`s thyroiditis and papillary thyroid carcinoma with coexisting Hashimoto`s thyroiditis.
Sex, Disease
View SamplesIn order to identify potential genes that may play an important role in progression of colorectal carcinoma, we screened and validated the global gene expression using cDNA expression array on 36 CRC tissues and compared with 24 non-cancerous colorectal tissue.
Genome-wide expression analysis of Middle Eastern colorectal cancer reveals FOXM1 as a novel target for cancer therapy.
Sex
View SamplesExperiment: Expression profiling in breast cancer brain metastases (BC) compared to breast cancers (BC) and primary brain tumors (prBT). The objectives are to identify expression profiles that are specific to BCBM in order to identify new molecular biomarkers. The characterization of the BCBM samples included adjacent genetic techniques.
Comprehensive molecular biomarker identification in breast cancer brain metastases.
Sex, Specimen part, Disease stage
View SamplesThere is growing evidence that transplantation of cadaveric human islets is an effective therapy for type 1 diabetes. However, gauging the suitability of islet samples for clinical use remains a challenge. We hypothesized that islet quality is reflected in the expression of specific genes. Therefore, gene expression in 59 human islet preparations was analyzed and correlated with diabetes reversal after transplantation in diabetic mice. Analysis yielded 262 differentially expressed probesets, which together predict islet quality with 83% accuracy. Pathway analysis revealed that failing islet preparations activated inflammatory pathways, while functional islets showed increased regeneration pathway gene expression. Gene expression associated with apoptosis and oxygen consumption showed little overlap with each other or with the 262 probeset classifier, indicating that the three tests are measuring different aspects of islet cell biology. A subset of 36 probesets surpassed the predictive accuracy of the entire set for reversal of diabetes, and was further reduced by logistic regression to sets of 14 and 5 without losing accuracy. These genes were further validated with an independent cohort of 16 samples. We believe this limited number of gene classifiers in combination with other tests may provide complementary verification of islet quality prior to their clinical use.
Gene expression signature predicts human islet integrity and transplant functionality in diabetic mice.
Specimen part
View SamplesGene regulatory networks that govern hematopoietic stem cells (HSC) and leukemiainitiating cells (L-IC) are deeply entangled. Thus, the discovery of compounds that target L-IC while sparing HSC is an attractive but difficult endeavor. Presently, most drug discovery approaches fail to counter-screen compounds against normal hematopoietic stem/progenitor cells (HSPC) to assess therapeutic index. Here, we present a combined in vitro and in vivo strategy to identify compounds specific to L-IC in acute myeloid leukemia (AML). A high-throughput screen of 4000 compounds on novel leukemia cell lines derived from human experimental leukemogenesis models yielded 80 hits, of which most were toxic to normal HSPC. Of the 10 compounds that passed this initial filter, we chose to characterize a single compound, kinetic riboside (KR), on AML L-IC and HSPC. KR demonstrated comparable efficacy to standard therapies against 63 primary AMLs. In vitro, KR effectively targeted the L-IC-enriched CD34+CD38- AML fraction, while sparing normal HSPC enriched fractions, although these effects were mitigated on HSC assayed in vivo, and highlights the importance of in vivo L-IC and HSC assays to measure function. Overall, we provide a novel approach to screen large drug libraries for the discovery of anti-L-IC compounds for human leukemias.
A small molecule screening strategy with validation on human leukemia stem cells uncovers the therapeutic efficacy of kinetin riboside.
Cell line, Treatment
View SamplesWe use the zebrafish embryo model to study the innate immune response against Staphylococcus epidermidis. Therefore, we injected S. epidermidis into the yolk at 2 hpf and took samples at 5 days post injection. Overall design: This deep sequence study was designed to determine the gene expression profile by Staphylococcus epidermidis infection. RNA was isolated from embryos at 5 days post injection. Wildtypes zebrafish embryos were micro-injected into the yolk (2hpf) with 20 CFU of S. epidermdis O-47 mCherry bacteria suspended in PVP (Polyvinylpyrrolidone), or Non-injected as a control. After injections embryos were transferred into fresh egg water and incubated at 28°C. At 5 days post injection 100-200 embryos per group were snap-frozen in liquid nitrogen, and total RNA was isolated using TRIZOL reagent.
Analysis of RNAseq datasets from a comparative infectious disease zebrafish model using GeneTiles bioinformatics.
No sample metadata fields
View SamplesWe use the zebrafish embryo model to study the innate immune response against Mycobacterium marinum. Therefore, we injected M. marinum into the yolk at the 64 cell stage and took samples at 5 days post injection. Overall design: This deep sequence study was designed to determine the gene expression profile by Mycobacterium marinum infection. RNA was isolated from embryos at 5 days post injection. Wildtypes zebrafish embryos were micro-injected into the yolk (64 cell stage) with 40 CFU of Mycobacterium marinum E11 mCherry bacteria suspended in PVP (Polyvinylpyrrolidone), or Non-injected as a control. After injections embryos were transferred into fresh egg water and incubated at 28°C. At 5 days post injection 50 embryos per group were snap-frozen in liquid nitrogen, and total RNA was isolated using TRIZOL reagent.
Analysis of RNAseq datasets from a comparative infectious disease zebrafish model using GeneTiles bioinformatics.
No sample metadata fields
View SamplesWe compared Agilent custom made expression microarrays with Illumina deep sequencing for RNA analysis of zebrafish embryos 5 days post fertilization, showing as expected a high degree of correlation of expression of a common set of 15,927 genes for untreated fish. The transcriptomes were also compared for fish injected in the yolk with Mycobacterium marinum Overall design: This RNA deep sequencing study was designed to determine the gene expression profile of zebrafish embryos 5 days post fertilization. We also have compared expression with embryos that were injected with Mycobacterium marinum in the yolk at 2 hours post fertilization. After injections embryos were transferred into fresh egg water and incubated at 28°C. 150 embryos of mock-injected embryos or 200 embryos injected with 12 CFU bacteria were snap-frozen in liquid nitrogen, and total RNA was isolated using TRIZOL reagent.
Analysis of RNAseq datasets from a comparative infectious disease zebrafish model using GeneTiles bioinformatics.
No sample metadata fields
View Samples