Transforming growth factor- (TGF-) is a key factor for the development of prostate cancer metastases in bone. In breast cancer and melanoma, studies have shown how TGF- regulates gene expression to allow cancer cells to adapt to the bone microenvironment.
The TGF-β Signaling Regulator PMEPA1 Suppresses Prostate Cancer Metastases to Bone.
Specimen part, Cell line, Treatment
View SamplesEnterotoxigenic Escherichia coli (ETEC) strains that produce both heat-stable (ST) and heat-labile (LT) enterotoxins cause severe post-weaning diarrhea in piglets. However, the relative importance of the individual enterotoxins to the pathogenesis of ETEC infection is poorly understood. In this study, we investigated the effect on virulence of an F4+ ETEC strain when removing some or all of its enterotoxins. Several isogenic mutant strains were constructed that lack the expression of LT in combination with one or both types of ST enterotoxins (STa and/or STb). Host early immune responses induced by these mutant strains 4h after infection were compared to the wild type strain GIS26 (O149:F4ac+, LT+ STa+ STb+). At the same time, the immune response of this wild type ETEC strain was compared to the mock-infected control, demonstrating the expression of porcine inflammatory response genes. For these purposes, the small intestinal segment perfusion (SISP) technique and microarray analysis were used and results were validated by qRT-PCR. We also measured net fluid absorption of pig small intestinal mucosa 4h after infection with wild type ETEC, the mutant strains and PBS (mock-infected). These data indicate an important role for STb in inducing small intestinal secretion early after infection. The microarray analysis of the different mutant strains also revealed an important role for STb in ETEC-induced immune response by the significant differential regulation of immune mediators like matrix metalloproteinase 3, interleukin 1 and interleukin 17. We conclude that STb can play a prominent role in ETEC-induced secretion and early immune response.
Role of heat-stable enterotoxins in the induction of early immune responses in piglets after infection with enterotoxigenic Escherichia coli.
Sex, Specimen part, Treatment
View SamplesAdam10, a cell surface protease, cleaving many proteins including TNF-alpha and E-cadherin. Here we investigate the genome wide effects of Adam10 knock out on the transcriptome.
The disintegrin/metalloproteinase Adam10 is essential for epidermal integrity and Notch-mediated signaling.
Specimen part
View SamplesThis study sought correlates of relapse tendency in TTP by examining gene expression profiles in peripheral blood leukocytes from patients with acquired ADAMTS13-deficient TTP in remission and matched healthy controls for global gene expression and autoantibodies.
Ribosomal and immune transcripts associate with relapse in acquired ADAMTS13-deficient thrombotic thrombocytopenic purpura.
Specimen part, Disease, Disease stage
View SamplesTSLP pathway blockade is a potential strategy for asthma treatment, as TSLP modulates cytokine production by mast cells and regulates the activation of dendritic cells (DCs), which prime the differentiation of nave T cells into inflammatory Th2 cells. To assess the effect of TSLPR blockade on the development of allergic inflammation and bronchoconstriction in Cynomolgus monkeys after Ascaris suum allergen challenge. Antibodies against human TSLPR were generated and confirmed to be cross-reactive to cynomolgus. Animals were dosed weekly with either vehicle (n=8) or TSLPR HuMAb (n=8) for 6 weeks and their responses to A.Suum challenge at baseline, week 2 and week 6 were assessed. Antibody-treated animals showed reduced bronchoalveolar lavage (BAL) eosinophil counts (p=0.04), reduced lung resistance (RL) area under the curve (p=0.04), and reduced IL-13 cytokine levels in BAL fluid (p=0.03) in response to challenge at 6 weeks compared to vehicle-treated animals. To understand the molecular changes underlying these differences, BAL fluid samples pre- and post-challenge were profiled using microarrays. Genes up-regulated by allergen challenge overlapped strongly with 11 genes up-regulated in DCs when stimulated by TSLP (TSLP-DC signature). The number of genes differentially expressed in response to challenge was reduced in aTSLPR-treated animals after 6 weeks relative to vehicle-treated animals. Expression of the TSLP-DC gene signature was also significantly reduced in aTSLPR-treated animals (p = 0.05). These results demonstrate promising efficacy for TSLPR blockade in an allergen challenge model where TSLP activation of DCs may play a key role.
Thymic stromal lymphopoietin receptor blockade reduces allergic inflammation in a cynomolgus monkey model of asthma.
Disease, Subject, Time
View SamplesCD20 is a clinically validated target for Non-Hodgkins lymphomas and autoimmune diseases. Interactions of CD20 with the B cell receptor (BCR) and components of the BCR signaling cascade have been reported. In this study we show that antibodies against CD20 or activation of the BCR by specific antibodies induce very similar expression patterns of up- or down-regulated genes in NHL cell lines indicating that CD20 may play a role in BCR signaling and vice versa.
Antibodies against CD20 or B-cell receptor induce similar transcription patterns in human lymphoma cell lines.
Cell line, Treatment
View SamplesBackground: Several genetic defects of the nucleotide excision repair (NER) pathway, including deficiency of the Excision Repair Cross-Complementing rodent repair deficiency, complementation group 1 (ERCC1), result in pre-mature aging, impaired growth, microcephaly and delayed development of the cerebellum. Such a phenotype also occurs in ERCC1-knockout mice which survive for up to 4 weeks after birth. Therefore, we analyzed cerebellar and hippocamapal transcriptomes of these animals at 3 weeks of age to identify the candidate mechanisms underlying brain consequences of reduced ERCC1 activity.
Downregulation of cholesterol biosynthesis genes in the forebrain of ERCC1-deficient mice.
No sample metadata fields
View SamplesTranscriptomes of mesenchymal stromal cells from bone marrow (bmMSC) were compared to MSC from term placenta (pMSC).
Expression of Desmoglein 2, Desmocollin 3 and Plakophilin 2 in Placenta and Bone Marrow-Derived Mesenchymal Stromal Cells.
Specimen part
View SamplesThese samples were all taken from patients who underwent investigations including colonoscopy but where all tests were normal and the diagnosis of irritable bowel syndrome was reached. These observations have been used as references in studies of colonic gene expression in inflammatory bowel diseases
Clinical phenotype and gene expression profile in Crohn's disease.
No sample metadata fields
View SamplesEpilepsy is a common cause of morbidity affecting approximately one third of patients with primary brain tumors. However, the molecular mechanism underlying the tumor induced epileptogenesis is poorly understood. The alteration in peritumoral microenvironments is believed to play a significant role in inducing epileptogenesis.
Transcriptomic profiling of human peritumoral neocortex tissues revealed genes possibly involved in tumor-induced epilepsy.
Sex, Specimen part, Disease, Disease stage
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