This SuperSeries is composed of the SubSeries listed below.
Radiogenomic Analysis of F-18-Fluorodeoxyglucose Positron Emission Tomography and Gene Expression Data Elucidates the Epidemiological Complexity of Colorectal Cancer Landscape.
Specimen part
View SamplesColorectal cancer is a highly heterogeneous disease, with variable molecular pathogenesis, involving multiple genomic and epigenetic alterations. Despite the significant advances in the diagnosis and treatment of colorectal cancer, it remains a major cause of morbidity and mortality, especially for countries in Northern America and Europe, as also in New Zealand & Australia. In this direction, the introduction of gene expression signatures derived from multiple layers of molecular & clinical dissection, may resolve the problems of heterogeneity and improve robust disease stratification
Radiogenomic Analysis of F-18-Fluorodeoxyglucose Positron Emission Tomography and Gene Expression Data Elucidates the Epidemiological Complexity of Colorectal Cancer Landscape.
Specimen part
View SamplesColorectal cancer is a highly heterogeneous disease, with variable molecular pathogenesis, involving multiple genomic and epigenetic alterations. Despite the significant advances in the diagnosis and treatment of colorectal cancer, it remains a major cause of morbidity and mortality, especially for countries in Northern America and Europe, as also in New Zealand & Australia. In this direction, the introduction of gene expression signatures derived from multiple layers of molecular & clinical dissection, may resolve the problems of heterogeneity and improve robust disease stratification.
Radiogenomic Analysis of F-18-Fluorodeoxyglucose Positron Emission Tomography and Gene Expression Data Elucidates the Epidemiological Complexity of Colorectal Cancer Landscape.
Specimen part
View SamplesGlobal gene expression analysis of grapevine cv. Pinot Noir berries during development and ripening. Time-course comparison of samples collected at three developmental stages (stages 33, 34 and 36 according to the modified E-L system, ref: Coombe BG, Aust J Grape Wine Res 1995, 1: 104-110) during three seasons (2003, 2005 and 2006).
Genome-wide transcriptional analysis of grapevine berry ripening reveals a set of genes similarly modulated during three seasons and the occurrence of an oxidative burst at vèraison.
Age, Specimen part, Time
View SamplesGlobal gene expression analysis of grapevine cv. Pinot Noir berries during development and ripening. Time-course comparison of samples collected at three developmental stages (stages 33, 34 and 36 according to the modified E-L system, ref: Coombe BG, Aust J Grape Wine Res 1995, 1: 104-110) during three seasons (2003, 2005 and 2006). Data for each of the three seasons were normalized independently within each season, using gcRMA.
Genome-wide transcriptional analysis of grapevine berry ripening reveals a set of genes similarly modulated during three seasons and the occurrence of an oxidative burst at vèraison.
Specimen part
View SamplesPancreatic ductal adenocarcinoma (PDA) is characterized by abundant desmoplasia and poor tissue perfusion. These features are proposed to limit access of therapies to neoplastic cells and blunt treatment efficacy. Indeed, several agents that target the PDA microenvironment promote chemotherapy delivery and improve anti-neoplastic responses in murine models of PDA. Here, we employed the FG-3019 monoclonal antibody directed against the pleiotropic matricellular signaling molecule connective tissue growth factor (CTGF/CCN2). FG-3019 treatment increased PDA cell killing and led to a dramatic tumor response without altering gemcitabine delivery. Microarray expression profiling revealed the down-regulation by FG-3019 of several anti-apoptotic transcripts, including the master regulator Xiap, down-regulation of which has been shown to sensitize PDA to gemcitabine. Decreases in XIAP protein by FG-3019 in the presence and absence of gemcitabine were confirmed by immunoblot, while increases in XIAP protein were seen in PDA cell lines treated with recombinant CTGF. Therefore, alterations in survival cues following targeting of tumor microenvironmental factors may play an important role in treatment responses in animal models and, by extension, PDA patients.
CTGF antagonism with mAb FG-3019 enhances chemotherapy response without increasing drug delivery in murine ductal pancreas cancer.
Sex, Specimen part, Treatment
View SamplesInflammatory hepatocellular adenomas (IHCA) are benign liver tumours defined by the presence of inflammatory infiltrates and by the elevated expression of inflammatory proteins in tumour hepatocytes1,2. Here we show a striking activation of the IL6 signalling pathway in this tumour type, and sequencing candidate genes pinpointed this response to somatic gain-of-function mutations in the IL6ST gene that encodes the signalling co-receptor gp130. Indeed, ~70% of IHCA harbour small in-frame deletions that target the binding site of gp130 for IL6, and expression of the most frequent gp130 mutant, Delta-STVY190, in hepatocellular cells activates STAT3 in absence of ligand. Further, analysis of hepatocellular carcinomas revealed rare gp130 alterations always accompanied by -catenin-activating mutations, suggesting a cooperative effect of these signalling pathways in the malignant conversion of hepatocytes. The recurrent gain-of-function gp130 mutations in these human hepatocellular adenomas explains their inflammatory phenotype, and suggest that similar alterations may occur in other inflammatory epithelial tumours with STAT3 activation.
Frequent in-frame somatic deletions activate gp130 in inflammatory hepatocellular tumours.
Sex, Specimen part, Disease
View SamplesThe aim of this study was to assess the relative gene expression in human AAA and AOD.
Differential gene expression in human abdominal aortic aneurysm and aortic occlusive disease.
Specimen part, Disease, Disease stage
View SamplesThe alveolar type 1 (AT1) cell covers >95% of the gas exchange surface and is extremely thin to facilitate passive gas diffusion. The development of this highly specialized cell is poorly understood including fundamental questions regarding cell number and morphology. Using new molecular stereology and single cell imaging methods, we show that AT1 cells develop via a non-proliferative two-step process while maintaining proliferative potential. In the flattening step, AT1 cells remodel cell junctions and undergo molecular specification. In the folding step, AT1 cells are sculptured to match secondary septa formation, resulting in a single AT1 cell spanning multiple alveoli. AT1 cells grow in size by >10-fold, fueling most of the postnatal lung growth. Strikingly AT1 cells proliferate upon ectopic SOX2 expression and undergo stage-dependent cell fate reprogramming. These results contradict the traditional view of AT1 cells being terminally differentiated and provide insights to alveolar maturation. In this experiment, we conducted next-generation sequencing on flow-sorter AT1 cells isolated from mouse lungs ectopically expressing Sox2 under the control of the AT1-specific promoter Scnn1a versus control AT1 cells. Overall design: Two samples of Sox2-expressing AT1 cells versus two control AT1 samples.
The development and plasticity of alveolar type 1 cells.
Cell line, Subject
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
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