In this data, we examined Transcriptome detection and expression in 8 samples of Retinoblastoma. We found a central core shared by all samples .
Discovery of a transcriptomic core of genes shared in 8 primary retinoblastoma with a novel detection score analysis.
Disease
View SamplesCancer growth and metastasis are regulated to a great extent by stromal cells within the tumor microenvironment. Tumor blood vessel components (endothelial cells and mural cells) are also ubiquitous within tumors, and yet, the impact of these tumor-resident cells is scarcely understood beyond oxygen and nutrients supply. Our hypothesis is that the interaction between stromal cells and tumor cells is bidirectional: tumor cells can modulate their peripheral environment that in turn becomes more favorable to tumor growth. To test this hypothesis, we analyzed the transcriptome of human pericytes and colon cancer cells after being cocultured for 48h in comparison with the same cells in monoculture.
No associated publication
Specimen part, Cell line
View SamplesMultiple Myeloma (MM) remains incurable, and new drugs with novel mechanisms of action are still needed. In this report, we have analyzed the action of Zalypsis, an alkaloid analogous to certain natural marine compounds, in MM. Zalypsis turned out to be the most potent antimyeloma agent we have tested so far, with IC50s from picomolar to low nanomolar ranges. It also showed remarkable ex vivo potency in plasma cells from patients and in MM cells in vivo xenografted in mice. Besides the induction of apoptosis and cell cycle arrest, Zalypsis provoked DNA double-strand-breaks (DSB), evidenced by an increase in phospho-Histone-H2AX and phospho-CHK2, followed by a striking overexpression of p53 in p53-wild type cell lines. In addition, in those cell lines in which p53 was mutated, Zalypsis also provoked DSB and induced cell death, although higher concentrations were required. Immunohistochemical studies in tumours also demonstrated Histone-H2AX phosphorylation and p53 overexpression. Gene expression profile studies were concordant with these results, revealing an important deregulation of genes involved in DNA-damage response. The potent in vitro and in vivo antimyeloma activity of Zalypsis uncovers the high sensitivity of tumour plasma cells to DSB, and strongly supports the use of this compound in MM patients.
Zalypsis: a novel marine-derived compound with potent antimyeloma activity that reveals high sensitivity of malignant plasma cells to DNA double-strand breaks.
No sample metadata fields
View SamplesIdentification of TLR4 as one of the most abundant RNA species in pericytes with respect to MSC, and corroboration of TLR4 expression on the cell surface, led us to obtain a comprehensive overview of the expression program of lipopolysaccharide (LPS) stimulated pericytes. Microarray analyisis demonstrated the significant upregulation of 76 annotated genes including transcripts for adhesion molecules, inflammation mediators, pro-angiogenic factors, transcription factors and anti-apoptotic proteins.
Lipopolysaccharide activates Toll-like receptor 4 (TLR4)-mediated NF-κB signaling pathway and proinflammatory response in human pericytes.
Specimen part, Treatment
View SamplesPericytes and mesenchymal stem cells (MSC) are ontogenically related, and in fact no phenotypic differences were observed by flow cytometry using a panel of surface antigen markers. Global gene expression profiles of human pericytes and MSC revealed that 43 genes were expressed more than 10 fold in pericytes as compared to MSC.
Lipopolysaccharide activates Toll-like receptor 4 (TLR4)-mediated NF-κB signaling pathway and proinflammatory response in human pericytes.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Impact of gene dosage on gene expression, biological processes and survival in cervical cancer: a genome-wide follow-up study.
Age
View SamplesThe contribution of copy number (CN)-altered genes in cervical carcinogenesis is unknown owing to a lack of correlation with gene expression. We mapped CN-altered genes in 31 cervical cancers (CCs), and investigated the expression of 21,000 genes in 55 CCs using microarrays. Biological processes associated with genes deregulated by gene dosage and the relationship between gene dosage and patient survival were investigated. CN-altered genome (CN-AG) percentages varied widely among tumors from 0% to 32.2% (mean = 8.1 8.9). Tumors were classified as low (mean = 0.5 0.6, n = 11), medium (mean = 5.4 2.4, n = 10), or high (mean = 19.2 6.6, n = 10) CN. The highest %CN-AG was found in 3q, which contributed an average of 55% of all CN alterations. Genome-wide, only 5.3% of CN-altered genes were deregulated by gene dosage; by contrast, the rate in fully duplicated 3q was twice as high. Amplification of 3q explained 23.6% of deregulated genes in whole tumors (r2 = 0.236, p = 0.006; analysis of variance), including those in 3q and other chromosomes. A total of 862 genes were deregulated exclusively in high-CN tumors, but only 22.9% were CN altered. This result suggests that the remaining genes are not deregulated directly by gene dosage but by mechanisms induced in trans by CN-altered genes. Anaphase-promoting complex/cyclosome (APC/C)-dependent proteasome proteolysis, glycolysis, and apoptosis were upregulated, whereas cell adhesion and angiogenesis were downregulated exclusively in high-CN tumors. The high %CN-AG and upregulated gene expression profiles of APC/C-proteasome-dependent proteolysis and glycolysis were associated with poor patient survival, although only the first 2 correlations were statistically significant (p < 0.05, log-rank test). The data suggest that inhibitors of APC/C-dependent proteasome proteolysis and glycolysis may be useful treatments in these patients.
Impact of gene dosage on gene expression, biological processes and survival in cervical cancer: a genome-wide follow-up study.
Age
View SamplesThis SuperSeries is composed of the SubSeries listed below.
DNA methylation fingerprint of neuroblastoma reveals new biological and clinical insights.
Specimen part
View SamplesAlthough Human papillomavirus infection is the main causal factor for cervical cancer (CC), there is data suggesting genetic factors could modulate the risk and progression of CC. Sibling studies suggest that maternally inherited factors could be involved in CC. To assess whether mitochondrial DNA (mtDNA) polymorphisms are associated to cervical cancer, HPV infection and HPV types, a case-control study was performed in the Mexican mestizo population. The polymorphism of mtDNA D-Loop was investigated in 187 cervical cancer patients and 270 healthy controls. D-loop was amplified from a blood DNA sample and analyzed by sequencing. HPV was detected and typed in cervical scrapes from both groups. mtDNA polymorphisms were compared in the whole samples and stratified by HPV types. The expression of 29 mitochondrial genes was analyzed in a subset of 45 tumor biopsies using the expression microarray ST1.0. The Amerindian haplogroup B2 increased the risk for CC (OR=1.6, 95% CI: 1.05-2.58) and showed an additive effect of 36% over the risk conferred by the HPV (OR=153, 95% CI: 65.4-357.5). The frequency of HPV 16, 18, 31 and 45 in cancer samples was similar in all haplogroups but one (D1). It showed a very low frequency of HPV16, any HPV18 and high frequency of HPVs 31, 45 and other types. Two mtDNA genes (MT-TD, MTTK) could be involved in the increased risk conferred by the haplogroup B2, since they were up-regulated exclusively in B2 tumors (p<0.05, t-test). These findings will contribute to clarify the importance of genetic factors in CC.
The Amerindian mtDNA haplogroup B2 enhances the risk of HPV for cervical cancer: de-regulation of mitochondrial genes may be involved.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Transcriptional shift identifies a set of genes driving breast cancer chemoresistance.
Sex, Age, Specimen part, Treatment
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