We are studying signaling pathways and growth properties of cultured human ovarian cancer cells that are expressing the G protein-coupled receptor, luteinizing hormone receptor (LHR),particularly interested in the changes that occur when the receptor is activated by its cognate ligand, gonadotropin (LH). To investigate these questions, we have employed the SKOV3 ovarian cancer cell line that has been stably transfected with LHR, and can then test the response of these cells in culture following exposure to LH.
Regulation of gene expression in ovarian cancer cells by luteinizing hormone receptor expression and activation.
Cell line, Treatment, Time
View SamplesThe synthetic supercooling drug, icilin, and its primary receptor target, the cation channel transient receptor potential (TRP) melastatin-8 (TRPM8), have been described as potent negative regulators of inflammation in the colon. The aim of this study was to determine whether the anti-inflammatory action of icilin could potentially be used to treat autoimmune neuroinflammatory disorders, such as multiple sclerosis (MS). During experimental autoimmune encephalomyelitis (EAE)a CD4+ T celldriven murine model of MSwe found that both wild-type (WT) and TRPM8-deficient EAE mice were protected from disease progression during icilin treatment, as evidenced by delays in clinical onset and reductions in neuroinflammation. In vitro, icilin potently inhibited the proliferation of murine and human CD4+ T cells, with the peripheral expansion of autoantigen-restricted T cells similarly diminished by the administration of icilin in mice. Attenuation of both TRPM8-/- and TRP ankyrin-1-/- T cell proliferation by icilin was consistent with the WT phenotype, which suggests a mechanism that is independent of these channels. In addition, icilin treatment altered the expressional profile of activated CD4+ T cells to one that was indicative of restricted effector function and limited neuroinflammatory potential. These findings identify a potent anti-inflammatory role for icilin in lymphocyte-mediated neuroinflammation and highlight clear pleiotropic effects of the compound beyond classic TRP channel activation.
The cooling compound icilin attenuates autoimmune neuroinflammation through modulation of the T-cell response.
Sex, Specimen part
View SamplesToxin A (TcdA) and Toxin B (TcdB), of the pathogen Clostridium difficile, are virulence factors that cause gross pathologic changes (e.g. inflammation, secretion, and diarrhea) in the infected host, yet the molecular and cellular pathways leading to observed host responses are poorly understood. To address this gap, TcdA and/or TcdB were injected into the ceca of mice and the genome-wide transcriptional response of epithelial layer cells was examined. Bioinformatic analysis of gene expression identified sets of cooperatively expressed genes. Further analysis of inflammation associated genes revealed dynamic chemokine responses.
In vivo physiological and transcriptional profiling reveals host responses to Clostridium difficile toxin A and toxin B.
No sample metadata fields
View SamplesWe are using the ACI rat model of 17beta-estradiol induced mammary cancer to define the mechanisms through which estrogens contribute to breast cancer development; identify and functionally characterize the genetic variants that determine susceptibility; and define the hormone-gene-environment interactions that influence development of mammary cancer in this physiologically relevant rat model. Female ACI rats are uniquely susceptible to development of mammary cancer when treated continuously with physiologic levels of 17beta-estradiol. Induction of mammary cancer in female ACI rats occurs through a mechanism that is largely dependent upon estrogen receptor-alpha. Interval mapping analyses of progeny generated in intercrosses between susceptible ACI rats and resistant Brown Norway (BN) rats revealed seven quantitative trait loci (QTL), designated Emca3 (Estrogen-induced mammary cancer) through Emca9, each of which harbors one or more genetic determinants of mammary cancer susceptibility. Genes that reside within Emca8 on RNO5 and were differentially expressed between 17beta-estradiol treated ACI and ACI.BN-Emca8 congenic rats were identified as Emca8 candidates.
Mapping of three genetic determinants of susceptibility to estrogen-induced mammary cancer within the Emca8 locus on rat chromosome 5.
Sex, Age, Specimen part
View SamplesHepatocyte-like cells (HLCs) are derived from human pluripotent stem cells (hPSCs) in vitro, but differentiation protocols commonly give rise to a heterogeneous mixture of cells. This variability confounds the evaluation of in vitro functional assays performed using HLCs. We demonstrate the purification of a sub-population of functional HLCs differentiated from multiple hPSC lines using the hepatocyte surface marker Asialoglycoprotein Receptor 1 (ASGR1).
Asialoglycoprotein receptor 1 is a specific cell-surface marker for isolating hepatocytes derived from human pluripotent stem cells.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
High-Risk Human Papillomavirus E7 Alters Host DNA Methylome and Represses HLA-E Expression in Human Keratinocytes.
Sex, Specimen part
View SamplesTo investigate the extent of gene expression dysregulation by the human papillomavirus (HPV) oncoprotein E7, we performed global gene expression analysis on normal immortalized keratinocytes from skin (NIKS),
High-Risk Human Papillomavirus E7 Alters Host DNA Methylome and Represses HLA-E Expression in Human Keratinocytes.
Sex, Specimen part
View SamplesToxin A and B from Clostridium difficile are the primary virulence factors in Clostridium difficile disease. The changes in gene transcription of human colon epithelial cells were investigated in vitro in order to better understand the many effects of both toxins.
Systems analysis of the transcriptional response of human ileocecal epithelial cells to Clostridium difficile toxins and effects on cell cycle control.
Cell line
View SamplesSquamous cell carcinoma (SCC) is the second most common cancer worldwide and accounts for approximately 30% of all keratinocyte cancers. The vast majority of cutaneous SCCs of the head and neck (cSCCHN) are readily curable with surgery and/or radiotherapy unless high-risk features are present. Perineural invasion (PNI) is recognized as one of these high-risk features. The molecular changes during clinical PNI in cSCCHN have not been previously investigated. In this study, we assessed the global gene expression differences between cSCCHN with or without incidental or clinical PNI. The results of the analysis showed signatures of gene expression representative of activation of p53 in tumors with PNI compared to tumors without, amongst other alterations. Immunohistochemical staining of p53 showed cSCCHN with clinical PNI to be more likely to exhibit a diffuse over-expression pattern, with no tumors showing normal p53 staining. DNA sequencing of cSCCHN samples with clinical PNI showed no difference in mutation number or position with samples without PNI, however a significant difference was observed in regulators of p53 degradation, stability and activity. Our results therefore suggest that cSCCHN with clinical PNI may be more likely to contain alterations in the p53 pathway, compared to cSCCHN without PNI.
Expression profiling of cutaneous squamous cell carcinoma with perineural invasion implicates the p53 pathway in the process.
Disease, Disease stage
View SamplesBACKGROUND: miRNA have been shown to play an important role during immune-mediated diseases such as inflammatory bowel disease. The aim of this study was to assess differential expression of miRNA between uninfected and infected mice with Clostridium difficile strain VPI 10463 RESULTS: MicroRNA (miRNA)-sequencing analysis indicated that miR-146b, miR-1940, and miR-1298 were significantly overexpressed in colons of C. difficile-infected mice Overall design: Colon of uninfected and C.difficile-infected C57BL6/J WT mice were sampled at day 4 post-infection with Clostridium difficile VPI 10463. The infection dose was 107 cfu/mouse.
Modeling the role of peroxisome proliferator-activated receptor γ and microRNA-146 in mucosal immune responses to Clostridium difficile.
Specimen part, Cell line, Subject
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