This SuperSeries is composed of the SubSeries listed below.
Cell-autonomous sex differences in gene expression in chicken bone marrow-derived macrophages.
Sex, Specimen part
View SamplesTo identify markers associated with inherent cellular sex-identity, we analysed cultured macrophages from male and female chick embryos. We found that male and female macrophages respond differently to stimulation by bacterial lipopolysaccharide and that female macrophages constitutively express higher levels of interferon target genes than male macrophages. To determine whether these differences resulted from the actions of gonadal hormones, we induced gonadal sex-reversal to alter the hormonal environment of the developing chick and analysed different tissues and macrophages from male and female embryos.
Cell-autonomous sex differences in gene expression in chicken bone marrow-derived macrophages.
Sex, Specimen part
View SamplesTo identify markers associated with inherent cellular sex-identity, we analysed macrophages from newly-hatched chicks. We found that male and female macrophages respond differently to stimulation by bacterial lipopolysaccharide and that female macrophages constitutively express higher levels of interferon target genes than male macrophages.
Cell-autonomous sex differences in gene expression in chicken bone marrow-derived macrophages.
Sex, Specimen part
View SamplesWhile infection of chickens with highly pathogenic avian influenza (HPAI) H5N1 subtypes often leads to complete mortality within 24 to 48 h, infection of ducks in contrast causes mild or no clinical signs. Rapid onsets of fatal disease in chickens, but with no evidence of severe clinical symptoms in ducks, suggest underlying differences in their innate immune mechanisms. To understand the molecular basis for such difference, chicken and duck primary lung cells, infected with a low-pathogenicity avian influenza (LPAI) and two HPAI H5N1 viruses, were subjected to RNA expression profiling using Affymetrix Chicken GeneChip arrays.
Highly pathogenic avian influenza virus infection in chickens but not ducks is associated with elevated host immune and pro-inflammatory responses.
Age, Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Using transcriptomics to guide lead optimization in drug discovery projects: Lessons learned from the QSTAR project.
Cell line, Treatment
View SamplesIn this paper we demonstrated the potential to flag toxicity issues by utilizing data from exploratory experiments which are typically generated for target evaluation purposes during early drug discovery
Using transcriptomics to guide lead optimization in drug discovery projects: Lessons learned from the QSTAR project.
Cell line, Treatment
View SamplesIn this paper we demonstrated the potential to flag toxicity issues by utilizing data from exploratory experiments which are typically generated for target evaluation purposes during early drug discovery
Using transcriptomics to guide lead optimization in drug discovery projects: Lessons learned from the QSTAR project.
Cell line, Treatment
View SamplesIn this paper we demonstrated the potential to flag toxicity issues by utilizing data from exploratory experiments which are typically generated for target evaluation purposes during early drug discovery
Using transcriptomics to guide lead optimization in drug discovery projects: Lessons learned from the QSTAR project.
Cell line, Treatment
View SamplesInterleukin-6 (IL-6) is an important growth factor for estrogen receptor-alpha (ER) positive breast cancer, and elevated serum IL-6 is associated with poor prognosis. We firstly demonstrated that pSTAT3 is the primary downstream IL-6 signaling pathway in ER-positive breast cancer, using ten different breast cancer cell lines. Three-dimensional cultures of these cell lines were also used to develop a 17-gene IL-6 specific gene signature that could be used to identify IL-6 driven disease. This signature included a variety of genes involved in immune cell function and migration, cell growth and apoptosis, and the tumor microenvironment. To further validate this IL-6 signature, we obtained 36 human ER-positive breast cancer tumor samples with matched serum for gene expression profiling and determination of an IL-6 pathway activation score (PAS). Patients with high IL-6 PAS were also enriched for elevated serum IL-6 (>=10 pg/ml). We then utilized a murine MCF-7 xenograft model to determine the role of IL-6 in ER-positive breast cancer and potential anti-IL-6 therapy in vivo. When IL-6 was administered in vivo, MCF-7 cells engrafted without the need for estrogen supplementation. Subsequently, we prophylactically treated mice at MCF-7 engraftment with an anti-IL-6 antibody (siltuximab), fulvestrant or combination therapy. Siltuximab alone was able to blunt MCF-7 engraftment. Similarly, when tumors were allowed to grow to 125 mm3 before treatment, siltuximab alone demonstrated tumor regressions in 90% (9/10) of tumors. Given the established role for IL-6 in ER+ breast cancer, this data demonstrates the potential for anti-IL-6 therapeutics.
Interleukin-6 is a potential therapeutic target in interleukin-6 dependent, estrogen receptor-α-positive breast cancer.
Specimen part
View SamplesWe measured transcriptional changes resulting from overexpression or downregulation of the GTPase Obg.
Obg and Membrane Depolarization Are Part of a Microbial Bet-Hedging Strategy that Leads to Antibiotic Tolerance.
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