This SuperSeries is composed of the SubSeries listed below.
Loss of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) induces apoptotic processes in pancreatic carcinoma cells.
Specimen part, Cell line
View SamplesEarly invasive growth and metastasis are features of pancreatic cancer that rely on resistance to anoikis, an apoptosis program activated upon loss of adequate matrix anchorage. Re-expression of the tumor suppressor p16 reversed anoikis resistance of pancreatic cancer cells. This conversion to an anoikis-susceptible phenotype was found to be associated with a striking loss of GNE mRNA expression, prompting us to address the role of GNE in pancreatic cancer in more detail. GNE catalyzes a rate-limiting key step of the sialic acid biosynthesis and may have additional functions in the nucleus.
Loss of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) induces apoptotic processes in pancreatic carcinoma cells.
Specimen part, Cell line
View SamplesEarly invasive growth and metastasis are features of pancreatic cancer that rely on resistance to anoikis, an apoptosis program activated upon loss of adequate matrix anchorage. Re-expression of the tumor suppressor p16 reversed anoikis resistance of pancreatic cancer cells. This conversion to an anoikis-susceptible phenotype was found to be associated with a striking loss of GNE mRNA expression, prompting us to address the role of GNE in pancreatic cancer in more detail. GNE catalyzes a rate-limiting key step of the sialic acid biosynthesis and may have additional functions in the nucleus.
Loss of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) induces apoptotic processes in pancreatic carcinoma cells.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Brain Endothelial- and Epithelial-Specific Interferon Receptor Chain 1 Drives Virus-Induced Sickness Behavior and Cognitive Impairment.
Sex, Specimen part, Treatment, Time
View SamplesVSV-M2 is recognized by cytosolic RIG-I. Notably, 5'-triphosphate RNA molecules derived from either viral RNA or from the synthetically produced 3pRNA can also induce RIG-I activation. MDA5 stimulation is achieved using complexed poly(I:C), a synthetic analog of viral dsRNA.
Brain Endothelial- and Epithelial-Specific Interferon Receptor Chain 1 Drives Virus-Induced Sickness Behavior and Cognitive Impairment.
Sex, Specimen part, Treatment, Time
View SamplesBrain endothelial cells are an essential part of the blood-brain-barrier (BBB) and, as such, are exposed to proinflammatory mediators as well as danger signals during infections. They might function as decisive cells mediating RNA virus- and IFN-mediated sickness behavior.
Brain Endothelial- and Epithelial-Specific Interferon Receptor Chain 1 Drives Virus-Induced Sickness Behavior and Cognitive Impairment.
Specimen part, Treatment, Time
View SamplesThe goal of this study was to identify the transcriptional mechanisms involved in the activation of the immune system by QS-21, a triterpene glycoside purified from the bark of Quillaja saponaria which has adjuvant activity in vivo. Saponins represent a promising class of vaccine adjuvant. Together with the TLR4-ligand MPL, QS-21 is part of the Adjuvant System AS01, a key component of the Malaria and Zoster candidate vaccines that display demonstrated clinical efficacy. However, the mechanism of action of QS-21 in this liposomal formulation is poorly understood. Upon intra-muscular immunisation, we observed that QS-21 rapidly accumulated in CD169+ resident macrophages of the draining lymph node where it elicited a local innate immune response. Depletion of these cells abrogated QS-21-mediated innate cell recruitment to the lymph node, dendritic cell (DC) phenotypic maturation as well as the adjuvant effect on T cell and antibody responses to co-administered antigens. DCs rather than lymph node-resident macrophages were directly involved in T cell priming by QS-21 as revealed by the decrease in antigen-specific T cell response in Batf3/ mice. Further analysis showed that the adjuvant effect of QS-21 depended on the integration of Caspase-1 and MyD88 pathways, at least in part through the local release of HMGB1. Taken together, this work unravels the key role of lymph node sentinel macrophage in controlling the adjuvant effect of a molecule proven to improve vaccine response in humans
Central Role of CD169<sup>+</sup> Lymph Node Resident Macrophages in the Adjuvanticity of the QS-21 Component of AS01.
Specimen part
View SamplesWe established gene expression profiles of diagnostic bone marrow samples of monozygotic twins with acute lymphoblastic leukemia. We established technical duplicates for each twin.
Prenatal origin of separate evolution of leukemia in identical twins.
Sex, Specimen part, Disease, Disease stage
View SamplesWe sequenced liver mRNA from 23 individual pigs (5 prefed and 18 fasted) taken at 4 separate time points to evaluate the change in gene expression over the course of hemorrhagic shock and resuscitation in response to a carbohydrate prefed state. Overall design: Examination of mRNA levels in liver biopsies from pigs at 4 timepoints throughout hemorrhagic shock and resuscitation
Fed state prior to hemorrhagic shock and polytrauma in a porcine model results in altered liver transcriptomic response.
Specimen part, Cell line, Subject, Time
View SamplesThe biology underlying nodal metastasis is poorly understood. Transcriptome profiling has helped to characterize both primary tumors seeding nodal metastasis and the metastasis themselves. The interpretation of these data, however, is not without ambiguities. Here we profiled the transcriptomes of 17 papillary thyroid cancer (PTC) nodal metastases, associated primary tumors and primary tumors from N0 patients. We also included patient-matched normal thyroid and lymph node samples as controls to address some limits of previous studies. We found that the transcriptomes of patient-matched primary tumors and metastases were more similar than of unrelated metastases/primary pairs, a result also reported in other organ systems, and that part of this similarity reflected patient background. We found that the comparison of patient-matched primary tumors and metastases was heavily confounded by the presence of lymphoid tissues in the metastasis samples. An original data adjustment procedure was developed to circumvent this problem. It revealed a differential expression of stroma-related gene expression signatures also regulated in other organ systems. The comparison of N0 vs. N+ primary tumors uncovered a signal irreproducible across independent PTC datasets. This signal was also detectable when comparing the normal thyroid tissues adjacent to N0 and N+ tumors, suggesting a cohort specific bias also likely to be present in previous studies with similar statistical power. Classification of N0 vs. N+ yielded an accuracy of 63%, but additional statistical controls not presented in previous studies, revealed that this is likely to occur by chance alone. To address this issue, we used large datasets from The Cancer Genome Atlas and showed that N0 vs. N+ classification rates could not be reached randomly for most cancers. Yet, it was significant, but of limited accuracy (<70%) for thyroid, breast and head and neck cancers.
Revisiting the transcriptional analysis of primary tumours and associated nodal metastases with enhanced biological and statistical controls: application to thyroid cancer.
Sex
View Samples