This SuperSeries is composed of the SubSeries listed below.
Progression of human bronchioloalveolar carcinoma to invasive adenocarcinoma is modeled in a transgenic mouse model of K-ras-induced lung cancer by loss of the TGF-β type II receptor.
Sex, Specimen part
View SamplesThe World Health Organization has subclassified adenocarcinoma based upon predominant cell morphology and growth pattern such as bronchioloalveolar carcinoma (BAC), adenocarcinoma with mixed subtypes (AC-mixed), and homogenously invasive tumors with a variety of histological patterns
Progression of human bronchioloalveolar carcinoma to invasive adenocarcinoma is modeled in a transgenic mouse model of K-ras-induced lung cancer by loss of the TGF-β type II receptor.
Sex, Specimen part
View SamplesRecent data suggests that repression of the Type II TGF-B Receptor (Tgfr2) repression in human lung adenocarcinoma is important for progression from noninvasive to invasive adenocarcinoma. To test this hypothesis in a animal model of non-invasive lung cancer, we generated an inducible, lung specific Tgfbr2 knockout model in the oncogenic Kras mouse.
Progression of human bronchioloalveolar carcinoma to invasive adenocarcinoma is modeled in a transgenic mouse model of K-ras-induced lung cancer by loss of the TGF-β type II receptor.
Specimen part
View SamplesRecent data suggests that repression of the Type II TGF-B Receptor (Tgfr2) repression in human lung adenocarcinoma is important for progression from noninvasive to invasive adenocarcinoma. To test this hypothesis in a animal model of non-invasive lung cancer, we generated an inducible, lung specific Tgfbr2 knockout model in the oncogenic Kras mouse.
Progression of human bronchioloalveolar carcinoma to invasive adenocarcinoma is modeled in a transgenic mouse model of K-ras-induced lung cancer by loss of the TGF-β type II receptor.
Specimen part
View SamplesThe role of myeloid cells in supporting cancer growth is well established. Most work has focused on myeloid-derived suppressor cells (MDSC) that accumulate in tumor-bearing animals, but tumor-associated neutrophils (TAN) are also known to be capable of augmenting tumor growth. However, little is known about their evolution, phenotype, and relationship to naive neutrophils (NN) and to the granulocytic fraction of MDSC (G-MDSC). In the current study, a transcriptomics approach was used in mice to compare these cell types. Our data show that the three populations of neutrophils are significantly different in their mRNA profiles with NN and G-MDSC being more closely related to each other than to TAN. Structural genes and genes related to cell-cytotoxicity (i.e. respiratory burst) were significantly down-regulated in TAN. In contrast, many immune-related genes and pathways, including genes related to the antigen presenting complex (e.g. all six MHC-II complex genes), and cytokines (e.g. TNF-a, IL-1-a/b), were up-regulated in G-MDSC, and further up-regulated in TAN. Thirteen of the 25 chemokines tested were markedly up-regulated in TAN compared to NN, including striking up-regulation of chemoattractants for T/B-cells, neutrophils and macrophages. This study characterizes different populations of neutrophils related to cancer, pointing out the major differences between TAN and the other neutrophil populations.
Transcriptomic analysis comparing tumor-associated neutrophils with granulocytic myeloid-derived suppressor cells and normal neutrophils.
No sample metadata fields
View SamplesFoxp3+ T-regulatory (Treg) cells maintain immune homeostasis and limit autoimmunity, but can also curtail host responses to cancers. Tregs are therefore promising targets to enhance anti-tumor immunity. Histone/protein acetyltransferases (HATs) promote chromatin accessibility, gene transcription and the function of multiple transcription factors and non-histone proteins. We found that conditional deletion or pharmacologic inhibition of one specific HAT, p300, in Foxp3+ Tregs, increased TCR-induced apoptosis in Tregs, impaired Treg suppressive function and iTreg peripheral conversion, and limited tumor growth in immunocompetent, but not in immunodeficient, hosts. Our data demonstrate that p300 is important for Foxp3+ Treg function and homeostasis in vivo and in vitro, and identify a novel mechanism to diminish Treg function without overtly impairing effector Tcell responses or inducing autoimmunity. Collectively, these data suggest a new approach for cancer immunotherapy.
Inhibition of p300 impairs Foxp3⁺ T regulatory cell function and promotes antitumor immunity.
Specimen part
View SamplesWe report a 29-gene diagnostic signature, which distinguishes individuals with NSCLC from controls with non-malignant lung disease with 91% Sensitivity, 79% Specificity and a ROC AUC of 92%. Accuracy on an independent set of 18 NSCLC samples from the same location was 79%. Samples from an independent location including 12 stage 1 NSCLC and 15 controls, achieved an accuracy of 74%. A study of 18 paired samples taken pre and post surgery shows that the PBMC associated cancer signature is significantly reduced after tumor removal, supporting the hypothesis that the signature detected in pre-surgery samples is a response to the presence of the tumor.
Gene expression profiles in peripheral blood mononuclear cells can distinguish patients with non-small cell lung cancer from patients with nonmalignant lung disease.
Sex, Age, Race
View SamplesMicroarry from Treg with conditional knockout of Usp7
Ubiquitin-specific Protease-7 Inhibition Impairs Tip60-dependent Foxp3+ T-regulatory Cell Function and Promotes Antitumor Immunity.
Specimen part
View SamplesHeritable differences in gene expression between individuals are an important source of phenotypic variation. The question of how closely the effects of genetic variation on protein levels mirror those on mRNA levels remains open. Here, we addressed this question by using ribosomal footprinting to examine how genetic differences between two strains of the yeast S. cerevisiae affect translation. Strain differences in translation were observed for hundreds of genes, more than half as many as showed genetic differences in mRNA levels. Similarly, allele specific measurements in the diploid hybrid between the two strains found roughly half as many cis-acting effects on translation as were observed for mRNA levels. In both the parents and the hybrid, strong effects on translation were rare, such that the direction of an mRNA difference was typically reflected in a concordant footprint difference. The relative importance of cis and trans acting variation on footprint levels was similar to that for mRNA levels. Across all expressed genes, there was a tendency for translation to more often reinforce than buffer mRNA differences, resulting in footprint differences with greater magnitudes than the mRNA differences. Finally, we catalogued instances of premature translation termination in the two yeast strains. Overall, genetic variation clearly influences translation, but primarily does so by subtly modulating differences in mRNA levels. Translation does not appear to create strong discrepancies between genetic influences on mRNA and protein levels. Overall design: Ribsosomal footprinting and RNASeq in the two yeast strains BY and RM as well as their diploid hybrid. We generated one library each for the BY and RM parents, and two libraries (biological replicates) for the hybrid data.
Genetic influences on translation in yeast.
Cell line, Subject
View SamplesEmbryonic chicken telencephalon nuclei were isolated for RNAseq to identify transcripts differentially expressed across different brain regions.
Neocortical Association Cell Types in the Forebrain of Birds and Alligators.
Sex, Specimen part
View Samples