Toca 511 is a modified Retroviral Replicating Vector based on Moloney g-retrovirus with an amphotropic envelope. As an investigational cancer treatment, Toca 511 preferentially infects cancer cells without direct cell lysis and encodes an enhanced yeast cytosine deaminase that converts the antifungal drug 5-fluorocytosine to the anticancer drug, 5-fluorouracil. A panel of established human cancers cell lines, derived from glioblastoma, colon, and breast cancer tissue was used to evaluate parameters critical for effective anticancer activity. As part of these analyses, we profiled relative mRNA levels across these cell lines via RNA sequencing. Overall design: mRNA expression profiles across nine human cancer cell lines.
Retroviral Replicating Vectors Deliver Cytosine Deaminase Leading to Targeted 5-Fluorouracil-Mediated Cytotoxicity in Multiple Human Cancer Types.
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View SamplesDifferentiation of human skeletal stem cells (hMSC) into osteoblasts is regulated by a few well described transcription factors. Our study used clustering and gene expression data to identify a novel transcription factor. ZNF25, which we showed is involved in osteoblast differentiation.
Transcription factor ZNF25 is associated with osteoblast differentiation of human skeletal stem cells.
Cell line
View SamplesZebrafish (Danio rerio) were obtained from the Zebrafish Research Facility maintained in the Center for Environmental Biotechnology at the University of Tennessee. Fish husbandry, spawning, and experimental procedures were conducted with approval from the University of Tennessee Institutional Animal Care and Use Committee (Protocol #1690-1007). Water for holding fish and conducting experiments (hereafter referred to as fish water) consisted of MilliQ water (Millipore, Bedford, MA) with ions added: 19 mg/L NaHCO3, 1 mg/L sea salt (Instant Ocean Synthetic Sea Salt, Mentor, OH), 10 mg/L CaSO4, 10 mg/L MgSO4, 2 mg/L KCl. Embryos were obtained by spawning adult fish with no history of contaminant exposure. Fertilization of embryos took place at the same time ( 15 min.), such that larvae used in experiments were of similar age at the time of exposure. All activities (maintenance of adult fish, spawning, and experiments) were conducted in an environmental chamber with a temperature of 27 1 C and 14:10h light:dark photoperiod.
Global gene expression profiling in larval zebrafish exposed to microcystin-LR and microcystis reveals endocrine disrupting effects of Cyanobacteria.
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View SamplesLocal protein synthesis in sensory neuron axons is necessary for axonal regeneration with the efficiency of regeneration decreasing with age. Because the full repertoire of transcripts in embryonic and adult rat sensory axons is unknown we asked how the pool of mRNAs dynamically changes during ageing. We isolated mRNA from pure axons and growth cones devoid of non-neuronal or cell body contamination. Genome-wide microarray analysis reveals that a previously unappreciated number of transcripts are localised in sensory axons and that this repertoire changes during development toward adulthood. Embryonic sensory axons are enriched in transcripts encoding cytoskeletal-related proteins with a role in axonal outgrowth. Surprisingly, adult axons are highly enriched in mRNAs encoding immune molecules with a role in nociception. To validate our experimental approach we show that Tubulin-beta3 mRNA is present only in embryonic axons where it is locally synthesised. In summary, we show that the population of axonal mRNAs dynamically changes during development, which may partly contribute to the intrinsic capacity of axons at different ages to regenerate after injury and to modulate pain.
Transcriptome analysis of embryonic and adult sensory axons reveals changes in mRNA repertoire localization.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Exosome transfer from stromal to breast cancer cells regulates therapy resistance pathways.
Cell line
View SamplesStromal communication with cancer cells can influence treatment response. We show that stromal and breast cancer (BrCa) cells utilize paracrine and juxtacrine signaling to drive chemotherapy and radiation resistance. Upon heterotypic interaction, exosomes are transferred from stromal to BrCa cells. RNA within exosomes, which are largely non-coding transcripts and transposable elements, stimulates the pattern recognition receptor RIG-I to activate STAT1-dependent anti-viral signaling. In parallel, stromal cells also activate NOTCH3 on BrCa cells. The paracrine anti-viral and juxtacrine NOTCH3 pathways converge as STAT1 facilitates transcriptional responses to NOTCH3 and expands therapy resistant tumor-initiating cells. Primary human and/or mouse BrCa analysis support the role of anti-viral/NOTCH3 pathways in NOTCH signaling and stroma-mediated resistance, which is abrogated by combination therapy with gamma secretase inhibitors. Thus, stromal cells orchestrate an intricate cross-talk with BrCa cells by utilizing exosomes to instigate anti-viral signaling. This expands BrCa subpopulations adept at resisting therapy and re-initiating tumor growth.
Exosome transfer from stromal to breast cancer cells regulates therapy resistance pathways.
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View SamplesStromal communication with cancer cells can influence treatment response. We show that stromal and breast cancer (BrCa) cells utilize paracrine and juxtacrine signaling to drive chemotherapy and radiation resistance. Upon heterotypic interaction, exosomes are transferred from stromal to BrCa cells. RNA within exosomes, which are largely non-coding transcripts and transposable elements, stimulates the pattern recognition receptor RIG-I to activate STAT1-dependent anti-viral signaling. In parallel, stromal cells also activate NOTCH3 on BrCa cells. The paracrine anti-viral and juxtacrine NOTCH3 pathways converge as STAT1 facilitates transcriptional responses to NOTCH3 and expands therapy resistant tumor-initiating cells. Primary human and/or mouse BrCa analysis support the role of anti-viral/NOTCH3 pathways in NOTCH signaling and stroma-mediated resistance, which is abrogated by combination therapy with gamma secretase inhibitors. Thus, stromal cells orchestrate an intricate cross-talk with BrCa cells by utilizing exosomes to instigate anti-viral signaling. This expands BrCa subpopulations adept at resisting therapy and re-initiating tumor growth.
Exosome transfer from stromal to breast cancer cells regulates therapy resistance pathways.
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View SamplesThe aim of this experiment was to investigate the regulation of gene expression by KLF3 and KLF8 in fetal erythroid cells by analyzing single and double mutant mouse models.
Generation of mice deficient in both KLF3/BKLF and KLF8 reveals a genetic interaction and a role for these factors in embryonic globin gene silencing.
Specimen part
View SamplesThe aim of this experiment was to investigate the role of KLF3 in regulating gene expression at different stages throughout the erythroid maturation process.
The CACCC-binding protein KLF3/BKLF represses a subset of KLF1/EKLF target genes and is required for proper erythroid maturation in vivo.
Specimen part
View SamplesThe aim of this experiment was to investigate the role of KLF1 in the fetal liver
The CACCC-binding protein KLF3/BKLF represses a subset of KLF1/EKLF target genes and is required for proper erythroid maturation in vivo.
Specimen part
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