A large amount of epidemiologic data supports a role for chronic inflammation in epithelial carcinogenesis. In the lung, several studies have found that smokers with chronic obstructive pulmonary disease (COPD), an inflammatory disease of the airways and alveoli, have an increased risk of lung cancer (1.3 to 4.9 fold) compared to smokers without COPD. We have also shown that COPD-like airway inflammation induced by an aerosolized lysate of non-typeable Hemophilus influenzae (NTHi) promotes lung cancer in a Clara cell-targeted K-ras mutant mouse model (CC-LR) of lung cancer. In contrast, existing epidemiologic data suggest that allergic inflammation of the airways may be protective against lung cancer. We tested this association in a mouse model of allergic airway inflammation. CC-LR mice were sensitized to ovalbumin by intraperitoneal injection weekly for two weeks, then challenged for 30 min to an aerosol of ovalbumin in 0.9% saline weekly for eight weeks. This resulted in eosinophilic lung inflammation associated with increased levels of T helper 2 (Th2) cytokines and mucous metaplasia of airway epithelium, similar to what is seen in asthma patients. However, consistent with epidemiologic data, this type of inflammation did not result in any significant differences in lung surface tumor number (22 3 in OVA exposed vs 26 6 in control mice). We conclude that asthma-like (Th2) inflammation does not promote lung carcinogenesis in a Ras-initiated background, and demonstrate a clear specificity for the nature of inflammation in lung cancer promotion. These findings will assist in determination of the essential cells and signaling events in lung cancer promotion by inflammation.
Interleukin 6, but not T helper 2 cytokines, promotes lung carcinogenesis.
Specimen part, Treatment
View SamplesSynapTRAP. Identification of Synaptic mRNA of neurons of the cortex. Technique combines sucrose percoll fractionation of a synaptically rich sample (SN) and TRAP tagged ribosome IP (PreIP and PostIP). This experiment uses pan neuronal SNAP25 mice and a cortical dissection. Overall design: Three replicates of four samples.
Transcriptomic Analysis of Ribosome-Bound mRNA in Cortical Neurites <i>In Vivo</i>.
Specimen part, Subject
View SamplesReconstitution of cytomegalovirus (CMV)-specific immunity following transplant remains a primary clinical objective to prevent CMV disease, and adoptive immunotherapy of CMV-specific T cells can be an effective therapeutic approach. Due to the persistence of CMV, most CMV-specific CD8+ T cells become terminally differentiated effector cells (TEFF). However, a minor subset retains a memory phenotype (TM). Interestingly, recent studies suggest that CMV-specific CD8+ T cells with different phenotypes may have different abilities to reconstitute sustained immunity following transfer. The immunology of human CMV (HCMV) infections is reflected in the mouse model of MCMV infection. We found that HCMV- and MCMV-specific T cells displayed shared genetic programs, validating the MCMV model for studies of CMV-specific T cells in vivo. After transfer, the proliferative capacity of MCMV-specific TM cells was vastly superior to TEFF cells. Strikingly, TM cells expanded and established sustained and diverse T cell populations even after multiple challenges. Although both TEFF and TM cells could protect Rag-/- mice, only TM cells could consistently survive after transfer into immune replete, latently infected recipients and respond if recipient immunity was lost. These data show that CMV-specific TM cells retain memory function during persistent infection and can re-establish CMV immunity when necessary.
Memory T cells specific for murine cytomegalovirus re-emerge after multiple challenges and recapitulate immunity in various adoptive transfer scenarios.
Specimen part
View SamplesWe report specific changes in schizophrenia developmental interneurons by genome-wide transcriptome analysis. Overall design: RNA sequencing analysis (bulk) of healthy control interneurons vs. schizophrenia interneurons. Fourteen independent iPSC lines per group with two independent differentiations
Dysregulated protocadherin-pathway activity as an intrinsic defect in induced pluripotent stem cell-derived cortical interneurons from subjects with schizophrenia.
Specimen part, Disease, Subject
View SamplesWe report down-regulation of protocadeherins in schizophrenia interneurons by genome-wide transcriptome analysis. Overall design: RNA sequencing analysis (bulk) of healthy control interneurons vs. schizophrenia interneurons. Four independent iPS lines per group (total 8 iPSC lines) with three independent differentiations
Dysregulated protocadherin-pathway activity as an intrinsic defect in induced pluripotent stem cell-derived cortical interneurons from subjects with schizophrenia.
Specimen part, Disease, Subject
View SamplesGenomewide analysis of gene expression associated with Tcof1 in mouse neuroblastoma. NB N1E-115 cells with wildtype, overexpression, knockdown of Tcof1.
Genomewide analysis of gene expression associated with Tcof1 in mouse neuroblastoma.
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View SamplesPericytes are integral components of the tissue vasculature and have essential functions in tumour angiogenesis. Endosialin (CD248) is a type I transmembrane glycoprotein highly expressed on pericytes in the tumour vasculature of most solid tumours, however it is low or negligibly expressed on normal tissue pericytes. Experiments using wild-type and endosialin-knockout mice has revealed that stromal endosialin expression facilitates intravasation of tumor cells from the primary tumor into the circulation, thereby promoting metastatic dissemination.
Endosialin-Expressing Pericytes Promote Metastatic Dissemination.
Sex, Specimen part, Disease
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Dynamic changes in 5-hydroxymethylation signatures underpin early and late events in drug exposed liver.
Sex, Specimen part, Treatment, Time
View SamplesDynamic changes in the mouse liver DNA methylome associated with short (1 day) and prolonged (7, 28 and 91 days) exposure to the rodent liver non-genotoxic carcinogen (NGC), phenobarbital (PB).
Dynamic changes in 5-hydroxymethylation signatures underpin early and late events in drug exposed liver.
Specimen part, Treatment
View SamplesHyperglycemia is an essential factor leading to micro- and macrovascular diabetic complications. Macrophages are key innate immune regulators of inflammation that undergo 2 major directions of functional polarization: classically (M1) and alternatively (M2) activated macrophages. The aim of the study was to examine the effect of hyperglycemia on transcriptional activation of M0, M1 and M2 human macrophages.
Hyperglycemia induces mixed M1/M2 cytokine profile in primary human monocyte-derived macrophages.
Specimen part, Treatment, Subject
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