Distinct processes govern the transition from myometrial quiescence to activation during both term and preterm labor. We sought the specific gene sets responsible for initiating term and preterm labor, along with a core set of effector genes necessary for labor independent of gestational age and the underlying trigger. The Effector Gene Set consisted of 49 genes present in both preterm and term labor but absent from non-labor samples. 122 genes were specific to preterm labor (Preterm Initiator Set) and 229 to term labor (Term Initiator Set). The Term Initiator and the Effector Sets reflected predominantly inflammatory processes. Surprisingly, the Preterm Initiator Gene Set reflected molecular and biological events almost exclusive of inflammation. Preterm and term labor differ dramatically in their unique, initiator gene profiles, suggesting alternative pathways underlie these events. Inflammatory processes are ubiquitous to the Term Initiator and the Effector Gene Sets, supporting the idea term parturition is an inflammatory process. The absence of inflammatory processes in the Preterm Initiator Set suggests inflammation is secondary to processes triggering spontaneous preterm birth, and could explain the lack of therapeutic efficacy associated with anti inflammatory/antibiotic regimens.
Human effector/initiator gene sets that regulate myometrial contractility during term and preterm labor.
Specimen part
View SamplesComparison of genome-wide mRNA expresson between tumor-infiltrating CD8+ T cells from the tumor (hypofunctional T cells) and periphery (functional T cells)
Molecular Profile of Tumor-Specific CD8+ T Cell Hypofunction in a Transplantable Murine Cancer Model.
Specimen part
View SamplesWe used high throughput sequencing to analyze the transcriptional profiling of EVT. By comparing the transcriptional profiling of EVT with or without H19 knockdown, numerous genes showed significantly altered expression as a result of H19 repression. Overall design: HTR cells were transfected with either control siRNA or siH19. 48h later after transfection, total RNA was extracted for library preparation and RNA-seq analysis to compare trancript profiles between siCon and siH19 cells.
H19 long noncoding RNA alters trophoblast cell migration and invasion by regulating TβR3 in placentae with fetal growth restriction.
Cell line, Subject, Time
View SamplesAbstract: Interleukin-10-deficient (Il10-/-) mice serve as a model for inflammatory bowel disease (IBD). The severity of colitis strongly depends on the inbred strain carrying the disrupted Il10 gene: C3H/HeJBir (C3) confers disease susceptibility, whereas C57BL/6J (B6) confers resistance. Genome-wide scans with microsatellite markers on segregrating backcross and F2 populations resulted in the detection of ten colitogenic quantitative trait loci (QTL). The aim of this study was to reduce the large number of candidate genes within the QTL intervals by identifying those genes which are located within the candidate gene intervals and which are differentially expressed in the colon of IBD-susceptible and -resistant strains. Using this combination of QTL mapping and microarray analysis, we identified 16 genes which were differentially expressed between B6- and C3-Il10-/- mice and were located within the candidate gene intervals. Three of these genes (Pla2g2a, Gbp1, Cd14) showed prominent differences in expression levels between B6- and C3-Il10-/- as well as between B6 and C3 wildtype mice and were considered to be major candidate genes. Pla2g2a and Gbp1 are known to be polymorphic between C3 and B6 mice. Expression data for Cd14 were confirmed by real-time RT PCR using specified pathogen free and germfree Il10-/- mice. In conclusion, the large number of candidate genes was reduced to three major candidates by using a combination of QTL mapping and microarray analysis. All three genes play an important role in inflammatory processes and immune response.
Cd14, Gbp1, and Pla2g2a: three major candidate genes for experimental IBD identified by combining QTL and microarray analyses.
No sample metadata fields
View SamplesWiskott-Aldrich syndrome (WAS) predisposes patients to leukemia and lymphoma. WAS is caused by mutations in the protein WASP which impair its interaction with the WIPF1 protein. Here, we aim to identify a module of WIPF1-coexpressed genes and to assess its use as a prognostic signature for colorectal cancer, glioma, and breast cancer patients. Two public colorectal cancer microarray data sets were used for discovery and validation of the WIPF1 co-expression module. Based on expression of the WIPF1 signature, we classified more than 400 additional tumors with microarray data from our own experiments or from publicly available data sets according to their WIPF1 signature expression. This allowed us to separate patient populations for colorectal cancers, breast cancers, and gliomas for which clinical characteristics like survival times and times to relapse were analyzed. Groups of colorectal cancer, breast cancer, and glioma patients with low expression of the WIPF1 co-expression module generally had a favorable prognosis. In addition, the majority of WIPF1 signature genes are individually correlated with disease outcome in different studies. Literature gene network analysis revealed that among WIPF1 co-expressed genes known direct transcriptional targets of c-myc, ESR1 and p53 are enriched. The mean expression profile of WIPF1 signature genes is correlated with the profile of a proliferation signature. The WIPF1 signature is the first microarray-based prognostic expression signature primarily developed for colorectal cancer that is instrumental in other tumor types: low expression of the WIPF1 module is associated with better prognosis.
An expression module of WIPF1-coexpressed genes identifies patients with favorable prognosis in three tumor types.
Sex, Age
View SamplesBackground Published multi-gene classifiers suggested outcome prediction for patients with stage UICC II colon cancer based on different gene expression signatures. However, there is currently no translation of these classifiers for application in routine diagnostic. Therefore, we aimed at validating own and published gene expression signatures employing methods which enable RNA and protein detection in routine diagnostic specimens. Results Immunohistochemistry was applied to 68 stage UICC II colon cancers to determine the protein expression of five selected previously published classifier genes (CDH17, LAT, CA2, EMR3, and TNFRSF11A). Correlation of protein expression data with clinical outcome within a 5-year post-surgery course failed to separate patients with a disease-free follow-up [Group DF] and relapse [Group R]). In addition, RNA from macrodissected tumor samples from 53 of these 68 patients was profiled on Affymetrix GeneChips (HG-U133 Plus 2.0). Prognostic signatures were generated by Nearest Shrunken Centroids with cross-validation. Although gene expression profiling allowed the identification of differentially expressed genes between the groups DF and R, a stable classification and prognosis signature was not discernable in our data. Furthermore, the application of previously published gene signatures consisting of 22 and 19 genes, respectively, to our gene expression data set using global tests and leave-one-out cross-validation was unable to predict clinical outcome (prediction rate 75.5% and 64.2%; n.s.). T-stage was the only independent prognostic factor for relapse in multivariate analysis with established clinical and pathological parameters including microsatellite status. Conclusions Our protein and gene expression analyses currently do not support application of molecular classifiers for prediction of clinical outcome in routine diagnostic as a basis for patient-orientated therapy in stage UICC II colon cancer. Further studies are needed to develop prognosis signatures applicable in patient care.
Molecular profiles and clinical outcome of stage UICC II colon cancer patients.
Sex
View SamplesPurified phage was used to prevent tumor growth in a mouse model of bacteria aggravated-colorectal cancer. Composite E. coli phage or vehicle control was added to the drinking water of specific pathogen free (SPF) APCmin mice and animals were colonized with E.coli NC101. APCmin mice displayed no overall difference in the number of tumors that formed within the small intestine, however colonization with E. coli NC101 accelerated the growth of tumors resulting in a significant increase in large tumor formation. Importantly, bacteriophage treatment of AIEC colonized APCmin animals significantly reduced E. coli colonization. Overall design: 4 week old APCmin heterozygous mice were given a cocktail of 3 E. coli phage in drinking water for 4 weeks, then challenged with E. coli NC101 via oral gavage biweekly for 2 weeks. Mice were then maintained on drinking water containing phage mixture for 2 months.
Expansion of Bacteriophages Is Linked to Aggravated Intestinal Inflammation and Colitis.
Specimen part, Cell line, Treatment, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Combined inhibition of receptor tyrosine and p21-activated kinases as a therapeutic strategy in childhood ALL.
Specimen part, Disease, Disease stage, Time
View SamplesThe purpose of this study was the principal investigation and frequency of RTK expression in primary T-ALLs. Primary initial T-ALLs were assessed regarding their transcriptome-wide expression profiles and screend for prominent RTK expression.
Combined inhibition of receptor tyrosine and p21-activated kinases as a therapeutic strategy in childhood ALL.
Disease, Disease stage
View SamplesDeregulated RTK activity has been implicated as a causal leukemogenic factor in the context of molecular aberrations that perturb differentiation in the hematopoietic lineage such as in childhood ALL. A deeper understanding of RTK signaling processes on a system-wide scale will be key in defining critical components of signaling networks. To link RTK activity with in vivo output in primary ALL we took a functional approach, which combined SH2 domain binding, mass spectrometry, and transcriptome analyses. Structure and composition of evolving networks were highly diverse with few generic features determined by receptor and cell type. A combinatorial assembly of varying context-dependent and few generic signaling components at multiple levels likely generates output specificity. PAK2 was identified as a phosphoregulated FLT3 target, whose allosteric inhibition resulted in apoptosis of ALL cells. Our studies provide evidence that a functional approach to leukemia signaling may yield valuable information for a network-directed intervention.
Combined inhibition of receptor tyrosine and p21-activated kinases as a therapeutic strategy in childhood ALL.
Specimen part, Time
View Samples