Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Regulation of gene expressions in vivo by anti-VEGF therapy

ABSTRACT: U87-EV human glioblastoma xenograft tumours is therapeutically treated by bevacizumab, a humanized anti-human VEGF mAb, when tumour is established in BALB/c SCID mice. At the end point, collect tumour samples and extracted total RNA for microarray to investigate the gene profile changes compared to control. These include the genes from human tumour cells and mouse host stroma cells. 3 control samples versus 3-bevacizumab treated samples

ORGANISM(S): Homo sapiens

SUBMITTER: Francesca Buffa

PROVIDER: E-GEOD-37956 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

A core human primary tumor angiogenesis signature identifies the endothelial orphan receptor ELTD1 as a key regulator of angiogenesis.

Masiero Massimo M Simões Filipa Costa FC Han Hee Dong HD Snell Cameron C Peterkin Tessa T Bridges Esther E Mangala Lingegowda S LS Wu Sherry Yen-Yao SY Pradeep Sunila S Li Demin D Han Cheng C Dalton Heather H Lopez-Berestein Gabriel G Tuynman Jurriaan B JB Mortensen Neil N Li Ji-Liang JL Patient Roger R Sood Anil K AK Banham Alison H AH Harris Adrian L AL Buffa Francesca M FM

Cancer cell 20130718 2

Limited clinical benefits derived from anti-VEGF therapy have driven the identification of new targets involved in tumor angiogenesis. Here, we report an integrative meta-analysis to define the transcriptional program underlying angiogenesis in human cancer. This approach identified ELTD1, an orphan G-protein-coupled receptor whose expression is induced by VEGF/bFGF and repressed by DLL4 signaling. Extensive analysis of multiple cancer types demonstrates significant upregulation of ELTD1 in tumo ...[more]

PMID: 23871637

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Project description:Adherence of pathogenic Escherichia coli strains to intestinal epithelia is essential for infection. For enterohemorrhagic E. coli (EHEC) serotype O157:H7, we have previously demonstrated that multiple factors govern this pathogenâs adherence to HeLa cells (39). One of these factors is CadA, a lysine decarboxylase, and this protein has been proposed to negatively regulate virulence in several enteric pathogens. In the case of EHEC strains, CadA modulates expression of the intimin, an outer membrane adhesin involved in pathogenesis. Here, we experimentally inactivated cadA in O157:H7 strain 86-24 to investigate the role of this gene in EHEC adhesion to tissue culture monolayers, global gene expression patterns, and colonization of the infant rabbit intestine. As expected, the cadA mutant did not possess lysine decarboxylation activity and was hyper-adherent to tissue-culture cells. Adherence of the cadA mutant was nearly 2-fold greater than that of the wt and complementation of the cadA defect reduced adherence back to wt levels. Furthermore, the cadA mutant affected the expression of intimin protein. Disruption of the eae gene (encoding the intimin protein) in the cadA mutant significantly reduced its adherence to tissue-culture cells. However, adherence of the cadA eae double mutant was greater than that of an 86-24 eae mutant, suggesting that the enhanced adherence of the cadA mutant is not entirely attributable to enhanced expression of intimin in this background. Gene array analysis revealed that the cadA mutation significantly altered EHEC gene expression patterns; expression of 1332 genes was down-regulated and 132 genes up-regulated in the mutant compared to the wild type strain. Interestingly, the gene expression variation shows an EHEC-biased gene alteration including intergenic regions. Two putative adhesins: flagella and F9 fimbriae were up-regulated in the cadA mutant, suggestive of their association with adherence in absence of the Cad regulatory mechanism. Remarkably, in the infant rabbit model, the cadA mutant out-competed the wild type strain in the ileum but not in the cecum or mid-colon, raising the possibility that CadA negatively regulates EHEC pathogenicity in a tissue-specific fashion. Experiment Overall Design: Arrays used as a starting point for further examination of the effects of the cadA deficiency. A limited number of biologically significant phenotypes and gene expression profiles were examined using qRT-PCR

Dataset Information

Regulation of gene expressions in vivo by anti-VEGF therapy

Publications

A core human primary tumor angiogenesis signature identifies the endothelial orphan receptor ELTD1 as a key regulator of angiogenesis.

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