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Biologic pathways associated with relapse in childhood acute lymphoblastic leukemia: a Children's Oncology Group study.
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View Samples35 paired samples from initial diagnosis and first marrow relapse. Genes and pathways differentiating diagnosis and relapse were identified. Potential therapeutic targets were also identified.
Biologic pathways associated with relapse in childhood acute lymphoblastic leukemia: a Children's Oncology Group study.
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View SamplesIt It is known that functional maturation of the small intestine occurring during the weaning period is facilitated by glucocorticoids (such as hydrocortisone, HC) including the increased expression of digestive hydrolases. However, the molecular mechanism(s) are not well understood, particularly in human gut. Here we report a microarray analysis of HC- induced changes in gene expression in H4 (a human fetal small intestinal epithelial cell line well-characterized in numerous previous studies). This study identified a large number of HC-affected genes, some involved in metabolism, cell cycle regulation, cell polarity, tight junction formation, and interactions with extracellular matrices. These effects could play an important role in HC-mediated enterocyte maturation in vivo and in vitro.
Hydrocortisone induces changes in gene expression and differentiation in immature human enterocytes.
Cell line, Treatment
View SamplesConjugated linoleic acid (CLA), a class of fatty acids found in beef and dairy products, has been shown to inhibit tumorigenesis in a variety of cancer model systems. Based on previously well-documented anti-tumor activity of CLA in rodent models of breast cancer, a pilot study was initiated to examine the effect of dietary CLA in a well-established transgenic model of breast cancer. Western blots were performed for the detection of AKT, c-Src, ERK1/2, and Cdc24. CLA significantly increased tumor burden (p<0.1) independent of an increase in oncogenic signaling. Mammary gland whole mounts indicated a loss of mammary adipose and extensive epithelial expansion in CLA-treated animals. Microarray analysis indicated a significant reduction in cytoskeletal related genes with at least a two-fold decrease in five out of six CLA-fed animals compared to untreated controls. Reduction of Cdc42, a key regulator of cell adhesion and cytoskeletal arrangements, was confirmed at the protein level by western blot (p<0.01). These findings suggest that dietary CLA may advance the malignant phenotype by promoting a loss of cell polarity and adhesion in the mammary gland epithelium. This action may have serious clinical implications for a subset high-risk population and warrants further investigation.
Pilot study on the effects of dietary conjugated linoleic acid on tumorigenesis and gene expression in PyMT transgenic mice.
Sex, Age, Specimen part
View SamplesIn our studies we were searching for the new factors engaged in mitochondrial nucleic acids metabolism under stress conditions in humans. Quantitative proteomic approach revealed C6orf203 protein as a potential new factor engaged in response to perturbed mitochondrial gene expression. We showed that C6orf203 is a mitochondrial RNA binding protein which is able to rescue diminished mitochondrial transcription in stress conditions. Overall design: The dataset corresponds to RNAseq studies and comprises experiment performed in triplicate. The aim of this study was to examine the influence of C6orf203 silencing on mitochondrial transcriptome. To this end we engineered two stable cell lines with the use of human 293 Flp-In T-Rex cells as parental. First cell line inducible expressed miRNAs silencing endogenous copy of C6orf203 gene while second one expressed additionally transgenic version of FLAG-tagged C6orf203 which contained silent mutations causing insensitivity to miRNA. We also analyzed RNA isolated from parental 293 Flp-In T-Rex cells. RNAseq libraries were prepared with the use of strand-specific library preparation procedures. RNAs were random fragmented and reverse transcribed using random oligomers as primers (dUTP-based protocol, see PMID: 29590189, PMID: 22609201; this pipeline enables analysis of RNAs (> ~100 nucleotides)). RNA was isolated from unfractionated cells using TRI-Reagent. Before preparation of the libraries total RNA was subjected to depletion of nuclear-encoded rRNAs (Ribo-Zero rRNA Removal Kit (Human/Mouse/Rat), Epicenter). Libraries were sequenced with the help of Illumina sequencing platform.
Quantitative proteomics revealed C6orf203/MTRES1 as a factor preventing stress-induced transcription deficiency in human mitochondria.
Specimen part, Subject
View SamplesA cell line was derived from a mammary carcinoma in the transgenic FVB/N-Tg(MMTV-ErbB2)NDL2-5Mul mouse. The line, referred to as “NDL(UCD)” is adapted to standard cell culture and can be transplanted into syngeneic FVB/N mice. The line maintains a stable phenotype over multiple in vitro passages and rounds of in vivo transplantation. The cell line exhibits high expression of ErbB2 and ErbB3 and signaling molecules downstream from ErbB2. The line was previously shown to be reactive to anti-immune checkpoint therapy with responses conducive to immunotherapy studies. Here, using both histology/immunophenotyping and gene expression/microarray analysis, we show that the syngeneic transplant tumors elicit an immune reaction in the adjacent stroma, with additional tumor infiltrating lymphocytes. We also show that this immune activating effect is greater in the syngeneic transplants than in the primary tumors arising in the native transgenic mouse. We further analyzed the PD-1 and PD-L-1 expression in the model and found PD-L1 expression in the tumors and in vitro. In conclusion these data document the validity and utility of this cell line for in vivo preclinical immunotherapy trials. Overall design: Flash frozen NDL(UCD) cell line tumor transplants were sampled and whole-transcriptome analysis was performed by next-generation sequencing (NGS)-based RNA-Sequencing. This series includes three biological replicates of the same cell line grown in three different (but same strain) mouse.
A Syngeneic ErbB2 Mammary Cancer Model for Preclinical Immunotherapy Trials.
Sex, Specimen part, Cell line, Subject
View SamplesGene Expression Classifiers for Minimal Residual Disease and Relapse Free Survival Improve Outcome Prediction and Risk Classification in Children with High Risk Acute Lymphoblastic Leukemia: A Children's Oncology Group Study
Gene expression classifiers for relapse-free survival and minimal residual disease improve risk classification and outcome prediction in pediatric B-precursor acute lymphoblastic leukemia.
Specimen part, Disease, Disease stage
View SamplesPAPER 1:"Identification of novel subgroups of high-risk pediatric precursor B acute lymphoblastic leukemia (B-ALL) by unsupervised microarray analysis: clinical correlates and therapeutic implications. A Children's Oncology Group (COG) study."
Gene expression classifiers for relapse-free survival and minimal residual disease improve risk classification and outcome prediction in pediatric B-precursor acute lymphoblastic leukemia.
Sex, Specimen part, Race
View SamplesLow affinity Tregs are important for controlling autoimmune diabetes. Overall design: High and low affinity Tregs were isolated from the spleen and pancreatic islets of two-TCR retrogenic mice expressing the insulin-specific TCRs 4-8 and 12-4.4m1.
Cutting Edge: Low-Affinity TCRs Support Regulatory T Cell Function in Autoimmunity.
Age, Specimen part, Subject
View SamplesWe have established AR3 transgenic mouse models with targeted expression of AR3 in the prostate using the ARR2PB promoter.
Androgen receptor splice variant AR3 promotes prostate cancer via modulating expression of autocrine/paracrine factors.
Age, Specimen part
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