This SuperSeries is composed of the SubSeries listed below.
Nanoemulsion mucosal adjuvant uniquely activates cytokine production by nasal ciliated epithelium and induces dendritic cell trafficking.
Sex, Age, Specimen part, Time
View SamplesAntigen uptake, processing and presentation by dendritic cells are regulated by complex intra- and inter-cellular signalling events. Typical vaccine adjuvants lead to the transcription of pro-inflammatory cytokines and chemokines which relate to immune induction.
Nanoemulsion mucosal adjuvant uniquely activates cytokine production by nasal ciliated epithelium and induces dendritic cell trafficking.
Sex, Age, Specimen part, Time
View SamplesThe efficacy and exceptionally good tolerance of estrogen blockade in the treatment of breast cancer is well recognized but novel agents are required, especially to take advantage of the multiple consecutive responses obtained in breast cancer progressing following previous hormone therapy, thus delaying the use of cytotoxic chemotherapy with its usually serious side effects. Acolbifene (ACOL) is a novel and unique antiestrogen completely free of estrogen-like activity in both the mammary gland and uterus while preventing bone loss. From the preclinical and clinical data so-far available, this new antiestrogen represents a unique opportunity for a highly potent and specific blockade of estrogen action in the mammary gland and uterus while exerting estrogen-like beneficial effects in other tissues (selective estrogen receptor modulator or SERM activity). In order to better understand the specificity of action of acolbifene, we have used Affymetrix GeneChips containing 45,000 probe sets to analyze 34,000 genes to determine the specificity of this compound compared to the pure antiestrogen fulvestrant, as well as the mixed antagonists/agonists tamoxifen and raloxifene to block the effect of estradiol (E2) and to induce effects of their own on gene expression in the mouse mammary gland. The genes modulated by E2 were those identified in two separate experiments and validated by quantitative real-time PCR (Q_RT-PCR). Three hours after the single subcutaneous injection of E2 (0.05 ug), the simultaneous administration of acolbifene, fulvestrant, tamoxifen and raloxifene blocked by 98%, 62%, 43% and 92% the number of E2-upregulated genes, respectively. On the other hand, 70%, 10%, 25% and 55% of the genes down-regulated by E2 were blocked by the same compounds. Acolbifene was also the compound which, when used alone, modulated the smallest number of genes also influenced by E2, namely 4%, thus possibly explaining the potent tumoricidal action of this compound in human breast cancer xenografts where 61% of tumors disappeared, thus bringing a new paradigm in the hormonal therapy of breast cancer.
Specific transcriptional response of four blockers of estrogen receptors on estradiol-modulated genes in the mouse mammary gland.
Specimen part, Treatment
View SamplesIschemic cardiopathy is the leading cause of death in the world, for which efficient regenerative therapy is not currently available. In mammals, after a myocardial infarction episode, the damaged myocardium is replaced by scar tissue featuring collagen deposition and tissue remodelling with negligible cardiomyocyte proliferation. Zebrafish, in contrast, display an extensive regenerative capacity as they are able to restore completely lost cardiac tissue after partial ventricular amputation. Due to the lack of genetic lineage tracing evidence, it is not yet clear if new cardiomyocytes arise from existing contractile cells or from an uncharacterised set of progenitors cells. Nonetheless, several genes and molecules have been shown to participate in this process, some of them being cardiomyocyte mitogens in vitro. Though questions as what are the early signals that drive the regenerative response and what is the relative role of each cardiac cell in this process still need to be answered, the zebrafish is emerging as a very valuable tool to understand heart regeneration and devise strategies that may be of potential value to treat human cardiac disease. Here, we performed a genome-wide transcriptome profile analysis focusing on the early time points of zebrafish heart regeneration and compared our results with those of previously published data. Our analyses confirmed the differential expression of several transcripts, and identified additional genes the expression of which is differentially regulated during zebrafish heart regeneration. We validated the microarray data by conventional and/or quantitative RT-PCR. For a subset of these genes, their expression pattern was analyzed by in situ hybridization and shown to be upregulated in the regenerating area of the heart. The specific role of these new transcripts during zebrafish heart regeneration was further investigated ex vivo using primary cultures of zebrafish cardiomyocytes and/or epicardial cells. Our results offer new insights into the biology of heart regeneration in the zebrafish and, together with future experiments in mammals, may be of potential interest for clinical applications.
Transcriptomics approach to investigate zebrafish heart regeneration.
Specimen part, Time
View SamplesNotch signaling is widely implicated in mouse mammary gland development and tumorigenesis. To investigate the effects of acute activation of Notch signaling in the mammary epithelial compartment, we generated bi-transgenic MMTV-rtTA; TetO-NICD1 (MTB/TICNX) mice that conditionally express a constitutively active NOTCH1 intracellular domain (NICD1) construct in the mammary epithelium upon doxycycline administration.
Notch promotes recurrence of dormant tumor cells following HER2/neu-targeted therapy.
Sex, Age, Specimen part, Treatment, Time
View SamplesWe recently found that the endoplasmic reticulum (ER) stress response (ERSR) is activated in surviving cardiac myocytes in a mouse model of in vivo myocardial infarction. ATF6 is an ER stress-activated transcription factor that induces ERSR genes, some of which encode proteins that may protect against ischemic damage. However, few ERSR genes have been identified in the heart, and there have been no gene expression profiling studies of ATF6-inducible genes, in vivo. We previously generated transgenic (TG) mice that express tamoxifen-activated ATF6, ATF6-MER, in the heart; ATF6-MER conferred tamoxifen-dependent ATF6 activation and protection from ischemic damage. To understand of the mechanism of ATF6-mediated cardioprotection, gene expression profiling of ATF6-MER TG mouse hearts was performed. Activated ATF6 changed expression levels of 1,162 genes in the heart; of the 775 ATF6-inducible genes, only 23 are known ERSR genes. One of the genes not expected to be induced by ATF6 is modulatory calcinuerin-interacting protein-1 (MCIP1). MCIP1 is induced in a calcineurin/NFAT-dependent manner during myocardial hypertrophy and it can feedback inhibit cardiomyocyte growth. We found that MCIP1 expression in cultured cardiomyocytes was increased by the prototypical ER stresser, tunicamycin (TM), or by simulated ischemia. Moreover, infecting cardiomyocytes with adenovirus encoding activated ATF6 induced MCIP1 expression and inhibited myocyte growth in response to the alpha 1-adrenergic agonist, phenylephrine. These results suggest that MCIP1 can be induced in the heart by ER stresses, such as ischemia. Moreover, b integrating hypertrophy and ER stress, MCIP-modulated myocyte growth may help rejuvenate nascent ER protein folding, which could contribute to protection from ischemic damage.
Coordination of growth and endoplasmic reticulum stress signaling by regulator of calcineurin 1 (RCAN1), a novel ATF6-inducible gene.
Sex, Age, Specimen part, Treatment
View SamplesWe analyzed expression changes between JAK2V617F positive bone marrow cells and JAK2V617F negative cells
Autocrine Tnf signaling favors malignant cells in myelofibrosis in a Tnfr2-dependent fashion.
Specimen part, Treatment
View SamplesHepatoblastoma (HB) is the most common pediatric liver tumor, and there are no targeted therapies available for children with HB. We have previously developed a murine model of HB which is driven by coactivation of the oncogenes YAP1 and -catenin (CTNNB1) [Tao J, Calvisi D, Ranganathan S, et al. Gastroenterology, 2014 Sep; 147(3): 690701]. We used the Sleeping Beauty transposase system combined with hydrodynamic tail vein injection to deliver plasmids containing mutant activated forms of YAP1 (YAP S127A) and -catenin (N90 -catenin) to a small number of pericentral hepatocytes. We have shown that these few transformed hepatocytes proliferate and dedifferentiate, eventually forming histologically heterogeneous tumors that resemble various subtypes of human HB (which is also highly heterogeneous), including areas of well-differentiated fetal, crowded fetal, embryonal, and blastemal HB. Our goal was to investigate how coactivation of YAP1 and -catenin drive the dedifferentiation of hepatocytes into hepatoblast-like tumor cells over time, leading to HB tumors. In order to measure changes in gene expression during tumorigenesis in our model, we used an Affymetrix microarray to analyze isolated RNA from wild type FVB mouse livers, mouse HB tumor tissue, and non-tumor liver tissue adjacent to HB tumors.
Hepatocyte-Derived Lipocalin 2 Is a Potential Serum Biomarker Reflecting Tumor Burden in Hepatoblastoma.
Age, Specimen part
View SamplesNIH-3T3 cells were pretreated for 15 min with either DMSO (mock) or cycloheximide followed by addition of either mock, 100 U/ml IFNalpha or 100 U/ml IFNgamma for 1h. During the last 30 min, 500 M 4-thiouridine was added to cell culture medium. Total cellular RNA was isolated using Trizol reagent and nascent RNA was purified as described (Dlken et al. RNA 2008) . Three replicates of nascent RNA were analyzed by Affymetrix Mouse Gene ST 1.0 arrays
Deciphering the modulation of gene expression by type I and II interferons combining 4sU-tagging, translational arrest and in silico promoter analysis.
Cell line
View SamplesNuocytes are a recently described cell that responds to both IL-25 and IL-33 and produce high levels of IL-13 and IL-5
Nuocytes represent a new innate effector leukocyte that mediates type-2 immunity.
Specimen part, Time
View Samples