We compared molecular characteristics of primary and recurrent pediatric ependymoma to identify sub-group specific differences.
Molecular sub-group-specific immunophenotypic changes are associated with outcome in recurrent posterior fossa ependymoma.
Specimen part
View SamplesWe sought to detect predictive markers related to a Src kinase inhibitor (saracatinib) sensitivity in ovarian cancer. Cell proliferation assays assigned 18 ovarian cancer cell lines to sensitive or resistant to this drug.
PTTG1 Levels Are Predictive of Saracatinib Sensitivity in Ovarian Cancer Cell Lines.
Specimen part
View SamplesAbnormal function of genes is at the root of most cancers, but heritable cancer syndromes account for a very small minority of all tumors in humans and domestic animals. The majority of cancers are sporadic, that is, they are not heritable in the strictest sense. Instead, sporadic cancers occur due to interactions of unknown intrinsic (heritable) and environmental factors that lead to malignant transformation and uncontrolled growth. Identification of heritable risk factors in sporadic human cancers is difficult because individual genetic backgrounds are very heterogeneous. To this end, individual genetic backgrounds of purebred dogs are more homogeneous, and dog breeds show different predilection to develop specific cancers. Here, we used genomic screens based on gene expression profiling to identify sets of genes that may contribute to the development of canine hemangiosarcoma, a relatively common endothelial sarcoma. Specific genes in a single breed (Golden Retrievers) are modulated by (or with) heritable risk traits, showing functional features that appear to modulate tumor behavior. Our results suggest these methods are suitable to identify genes that will enhance our understanding of how these cancers happen, as well as possible treatment targets that will improve outcomes of both human and canine cancer patients.
Innate immune response to influenza A virus in differentiated human alveolar type II cells.
Specimen part, Subject, Time
View SamplesThe gastrointestinal tract is a major site of early HIV-1 replication and death of CD4+ T cells. As HIV-1 replicates in the gut, the protective epithelial barrier gets disrupted, leading to the entry of bacteria into the underlying tissue and the bloodstream, leading to inflammation and clinical complications even in HIV-1-infected patients taking antiviral drugs. Counteracting these pathogenic processes may require in-depth understanding of the molecular pathways that HIV-1 and microbes utilize to infect, functionally alter and/or kill CD4+ T cells. However, to date, the nature of the genes altered by relevant HIV-1 strains and bacteria in intestinal CD4+ T cells remains unclear.
The transcriptome of HIV-1 infected intestinal CD4+ T cells exposed to enteric bacteria.
Specimen part, Subject
View SamplesWe previously identified toll-like receptor 4 (Tlr4) as a candidate gene responsible for ozone (O3)-induced pulmonary hyperpermeability and inflammation. The objective of this study was to determine the mechanism through which TLR4 modulates O3-induced pulmonary responses and to utilize transcriptomics to determine TLR4 effector molecules. C3H/HeJ (HeJ; Tlr4 mutant) and C3H/HeOuJ (OuJ; Tlr4 normal), mice were exposed continuously to 0.3 ppm O3 or filtered air for 6, 24, 48 or 72 hr. Affymetrix Mouse430A_MOE gene arrays were used to analyze lung homogenates from HeJ and OuJ mice followed using a bioinformatic analysis. Inflammation was assessed by bronchoalveolar lavage and molecular analysis by ELISA, immunoblotting, and transcription factor activity. TLR4 signals through both the MYD88-dependent and independent pathways in OuJ mice, which involves MAP kinase activation, NF-kappaB, AP-1, and KC. Microarray analyses identifiedTLR4 responsive genes for strain and time in OuJ versus HeJ mice (p<0.05). One significantly upregulated cluster of genes in OuJ were the heat shock proteins (Hspa1b; Hsp70), Hsp90ab1). Furthermore, O3-induced expression of HSP70 protein was increased in OuJ compared to HeJ mice following 24-48 h O3. Moreover, BAL polymorphonuclear leukocytes (PMN) and total protein were significantly reduced in response to O3 in Hspa1a/Hspa1btm1Dix (Hsp70-/-) compared to Hsp70+/+ mice (p<0.05). TLR4 signaling (MYD88-dependent), ERK1/2, AP-1 activity, and KC protein content were also significantly reduced after O3 exposure in Hsp70-/- compared to Hsp70+/+ mice (p<0.05). These studies suggest that HSP70 is involved in the regulation of O3-induced lung inflammation through the TLR4 pathway and provide evidence that HSP70 is an endogenous in vivo TLR4 ligand.
Identification of candidate genes downstream of TLR4 signaling after ozone exposure in mice: a role for heat-shock protein 70.
Sex, Specimen part, Treatment
View SamplesThe objective of this study was to determine the effect of Thyroid Hormone Responsive Protein Spot14 (Spot14) overexpression on the gene expression profiles of tumors from MMTV-Neu mice. Hemizygous MMTV-Neu and MMTV-Spot14 mice were bred and 1 cm tumors from Neu control or Neu/Spot14 bitransgenic offspring were profiled using Affymetrix gene arrays. Tumors from Neu/Spot14 mice emerged significantly earlier than controls, but expressed many genes associated with lactogenic differentiation and were not highly metastatic. These results from the mouse model are consistent with observations from primary human breast tumors, which indicate that high Spot14 gene expression was directly correlated with a luminal subtype and a positive ER status. Overexpression of Spot14 in cultured mammary epithelial cells stimulated proliferation but not differentiation. Together, these data suggest that, in vivo, Spot14 is expressed in well-differentiated cells, and promotes the expansion of this population in the context of oncogenic signaling pathway activation.
Modulation of tumor fatty acids, through overexpression or loss of thyroid hormone responsive protein spot 14 is associated with altered growth and metastasis.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Protective role of IL-6 in vascular remodeling in Schistosoma pulmonary hypertension.
Sex, Specimen part, Disease, Disease stage, Treatment
View SamplesPrimary breast cancer xenografts
No associated publication
Treatment
View SamplesLow molecular weight polycyclic aromatic hydrocarbons (LMW PAHs) are generated by the incomplete combustion of organic material and are prevalent and ubiquitous in the environment, presenting a human health concern. While much is known about the high molecular weight genotoxic species of PAHs, there are insufficient studies for LMW PAHs and their impact on pulmonary health. Secondhand smoke, or environmental tobacco smoke (ETS), is a mixture of many PAHs, among other constituents. To study the effect of more than one PAH, we examined single PAH and a binary mixture on the dysregulation of gap junctional intercellular communication (GJIC), activation of mitogen activated protein kinases (MAPK), and induction of inflammation with a focus on the p38 MAPK pathway through transcriptomic analysis. A mouse non-tumorigenic alveolar type II cell line, C10, along with two normal, non-tumorigenic human bronchial epithelial cell lines, Beas2b and HBE1 cells, for human comparisons. Our findings in all cell lines indicate that 1-methylanthracene (1-MeA) and fluoranthene (Flthn), can dysregulated GJIC in a dose dependent manner and combining these two compounds lead to a similar effect on GJIC. MAPKs, particularly P38, are rapidly activated and the inhibition of this MAPK leads to a reversal of PAH dysregulation of GJIC. A toxicogenomic approach conducted using the C10 cells revealed inflammatory, metabolic, steroid synthesis, and oxidative pathways altered synergistically by a mixture of PAHs (1-MeA and Flthn), followed by qRT-PCR, ELISAs, and immunoblots validation. Our findings indicated LMW PAHs potential to induce pulmonary inflammation and emphasize the need for mixture exposure research to accurately estimate human exposure risk.
No associated publication
Specimen part, Cell line, Time
View SamplesLesions of chronic idiopathic urticaria (CIU) showed significant up-regulation of 506 genes and reduced expression of 51 genes.
Gene expression profiles in chronic idiopathic (spontaneous) urticaria.
Specimen part, Subject
View Samples