Purpose: To explore the side population (SP) in pancreatic ductal adenocarcinoma (PDAC) for its gene expression profile and its association to cancer stem cells (CSC) and to evaluate the value of genes from its gene signature on patient survival.
Human pancreatic cancer contains a side population expressing cancer stem cell-associated and prognostic genes.
Sex, Age, Specimen part, Disease stage
View SamplesAstrocyte-secreted proteins induce synapse formation between isolated retinal ganglion cell (RGC) neurons in culture. We asked whether 2 of these proteins, glypican 4 (Gpc4) or thrombospondin 1 (TSP1) induce synapse formation by regulating gene expression in RGCs.
Astrocyte-Secreted Glypican 4 Regulates Release of Neuronal Pentraxin 1 from Axons to Induce Functional Synapse Formation.
Treatment
View SamplesMutations affecting the RAS-MAPK pathway frequently occur in relapse neuroblastoma tumors, which suggests that activation of this pathway is associated with a more aggressive phenotype. To explore this hypothesis we generated several model systems to define a neuroblastoma RAS-MAPK pathway signature. We could show that activation of this pathway in primary tumors indeed correlates with poor survival and is associated with known activating mutations in ALK and other RAS-MAPK pathway genes. From integrative analysis we could show that mutations in PHOX2B, CIC and DMD are also associated with an activated RAS-MAPK pathway. Mutation of PHOX2B and deletion of CIC in neuroblastoma cell lines induces activation of the RAS-MAPK pathway. This activation was independent of phosphorylated ERK in the CIC knock out systems. Furthermore, deletion of CIC causes a significant increase in tumor growth in vivo. These results show that the RAS-MAPK pathway is involved in tumor progression, and establish CIC as a powerful tumor suppressor that functions downstream of this pathway in neuroblastoma.
RAS-MAPK Pathway-Driven Tumor Progression Is Associated with Loss of CIC and Other Genomic Aberrations in Neuroblastoma.
Cell line
View SamplesExpression profiling using a defined set of iron regulated genes identifies co-regulation of genes and pathways related to inflammatory cytokines
Iron, inflammation, and early death in adults with sickle cell disease.
Specimen part, Disease
View SamplesTo evaluate the prognostic relevance of molecular subtypes and key transcription factors in pancreatic ductal adenocarcinoma (PDAC), we performed gene expression analysis of whole-tumor tissue obtained from 118 surgically resected PDAC and 13 control samples.
Prognostic relevance of molecular subtypes and master regulators in pancreatic ductal adenocarcinoma.
Specimen part
View SamplesTo unravel the molecular mechanisms mediating the effects of androgens on spermatogenesis, testicular gene expression was compared in mice with a Sertoli cell-selective androgen receptor knockout (SCARKO) and littermate controls on postnatal d 10. At this age testicular cell composition is still comparable in SCARKOs and controls. Microarray analysis identified 692 genes with significant differences in expression. A more than 2-fold up- or downregulation by androgen action in Sertoli cells was observed for 28 and 6 genes respectively. The biological relevance of the strongly upregulated genes was supported by the finding that several of them were previously described to be androgen-regulated or essential for spermatogenesis. Serine protease inhibitors were overrepresented in the same subgroup suggesting a role for androgens in cell junction dynamics and tissue restructuring events during spermatogenesis. A time course experiment (d8-d20), followed by cluster analysis allowed the identification of typical expression patterns of differentially expressed testicular genes during initiation of spermatogenesis. Three genes with a pattern closely resembling that of Pem, a prototypal androgen-regulated gene in Sertoli cells, were selected for confirmation by RT-PCR and further analysis. The data confirm that the SCARKO model allows identification of novel androgen-regulated genes in the testis. This particular series represents all data from d 10. The additional expression data from the time course (d8-d20) is represented by series GSE2259 ("Testicular gene expression in SCARKO mice during prepuberty").
The effect of a sertoli cell-selective knockout of the androgen receptor on testicular gene expression in prepubertal mice.
No sample metadata fields
View SamplesTo unravel the molecular mechanisms mediating the effects of androgens on spermatogenesis, testicular gene expression was compared in mice with a Sertoli cell-selective androgen receptor knockout (SCARKO) and littermate controls on postnatal d 10. At this age testicular cell composition is still comparable in SCARKOs and controls. Microarray analysis identified 692 genes with significant differences in expression. A more than 2-fold up- or downregulation by androgen action in Sertoli cells was observed for 28 and 6 genes respectively. The biological relevance of the strongly upregulated genes was supported by the finding that several of them were previously described to be androgen-regulated or essential for spermatogenesis. Serine protease inhibitors were overrepresented in the same subgroup suggesting a role for androgens in cell junction dynamics and tissue restructuring events during spermatogenesis. A time course experiment (d8-d20), followed by cluster analysis allowed the identification of typical expression patterns of differentially expressed testicular genes during initiation of spermatogenesis. Three genes with a pattern closely resembling that of Pem, a prototypal androgen-regulated gene in Sertoli cells, were selected for confirmation by RT-PCR and further analysis. The data confirm that the SCARKO model allows identification of novel androgen-regulated genes in the testis.
The effect of a sertoli cell-selective knockout of the androgen receptor on testicular gene expression in prepubertal mice.
No sample metadata fields
View SamplesIn clinical trials assessing neoadjuvant androgen deprivation therapy plus next-generation androgen receptor axis inhibitors, a subset of patients fail to demonstrate a complete pathologic response following treatment and radical prostatectomy. We performed transcriptome analyses on laser capture microdissected foci of residual tumor from these patients.
Neoadjuvant-Intensive Androgen Deprivation Therapy Selects for Prostate Tumor Foci with Diverse Subclonal Oncogenic Alterations.
Specimen part, Treatment
View SamplesOne third to one half of all infants born before the 28th wek of gestation develop BPD bronchopulmonary dysplasia. Our objective is to evaluate the feasibility of using expression profiling in umbilical cord tissue to discover molecular signatures for developmental staging and for risk of BPD.
Perturbation of gene expression of the chromatin remodeling pathway in premature newborns at risk for bronchopulmonary dysplasia.
No sample metadata fields
View SamplesCells undergoing apoptosis are known to modulate their tissue microenvironments. By acting on phagocytes, notably macrophages, apoptotic cells inhibit immunological and inflammatory responses and promote trophic signaling pathways. Paradoxically because of their potential to cause death of tumor cells and thereby militate against malignant disease progression, both apoptosis and tumor-associated macrophages (TAM) are often associated with poor prognosis in cancer. In order to better understand the influence of tumor cell apoptosis and in particular its effect on TAM, we investigated global gene expression signatures of undisturbed TAM engaged in engulfment of apoptotic tumor cells. We studied a xenograft model of an aggressive starry-sky non-Hodgkins lymphoma, Burkitts lymphoma (BL), in which apoptotic tumor cells are common and frequently observed in association with the starry-sky TAM (SS-TAM, so called because they appear histologically as stars in a sky of tumor cells) that accumulate in these tumors. We used a BL cell line (BL2) whose cells phenotypically resemble the tumor biopsy cells from which the line was derived including the capacity to undergo apoptosis constitutively. BL xenografts in SCID mice closely recapitulated the starry-sky histological picture of the human lymphoma. Due to the high sensitivity of macrophages to their environments, we adopted laser-capture microdissection of individual SS-TAM in BL xenografts in order to obtain unbiased in situ transcriptional profiles of these cells, which we compared specifically with those of similarly-captured macrophages, the tingible-body macrophages from normal germinal centers (GCM). The rationale for this comparison was based upon BL being a germinal center malignancy and tingible-body macrophages being regarded as normal equivalents of SS-TAM.
Oncogenic properties of apoptotic tumor cells in aggressive B cell lymphoma.
Sex, Specimen part
View Samples