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VEGFA | bioCADDIE Data Discovery Index
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biomedical and healthCAre Data Discovery Index Ecosystem
biomedical and healthCAre Data Discovery Index Ecosystem
uster of genes including LIN28B, IL-6, HMAGA2 and VEGFA. This finding links well to an established regulatory axis involving LIN28B, Let-7 microRNA, and IL-6 in inflammation and cell transformation that is regulated by NF-kB. Exponentially growing U87-MG cells were stably transfected with an empty vector (V0) or vectors coding for Myc-KPC1 or Flag-p50. Cells were dissociated with trypsin, washed with PBS, and brought to a concentration of 50×10^6 cells/ml. Cell suspension (5×10^6/0.1 ml) was inoculated subcutaneously at the right flank of 7-weeks old male Balb/C nude mice (n=7). Following 21 days, mRNA from U87-MG xenografts was isolated using an RNA purification kit, and analyzed using the Illumina HiSeq 2500 sequencer. The RNASeq analysis experiment was repeated twice independently. Run1 included a total of 7 samples. Samples 1-3 were isolated from V0 – control tumors (3 different tumors), samples 4-5 were isolated from KPC1-expressing tumors (2 different pools of 3 tumors each due to small tumor size), and samples 6-7 were isolated from p50-expressing tumors for (2 different pools of 2-3 tumors each, due to very small tumor size). Run2 included a total of 5 samples. Samples 8-10 were isolated from V0 (control) tumors (3 different tumors), samples 11-12 were isolated from KPC1 tumors (2 different pools of 3 tumors each due to small tumor size). Several re...
, as were a number of Wnt target genes, including VEGFA, CCND1, MMP7, CLDN1, SOX9, RHOU (all p<0.05 compared to healthy nonsmokers). As a mechanism to explain this broad, smoking-induced suppression of the Wnt pathway, we assessed expression of the DKK and SFRP families, extracellular regulators that suppress the Wnt pathway. Among these, secreted frizzled-related protein 2 (SFRP2), was up-regulated 4.3-fold (p<0.0001) in healthy smokers and 4.9-fold (p<0.0001) in COPD smokers, an observation confirmed by TaqMan Real-time PCR. AT the protein levels, Western analysis demonstrated SFRP2 up-regulation, and immunohistochemistry demonstrated that the smoking-induced SFRP2 upregulation occurred in differentiated ciliated cells. Finally, cigarette smoke extract mediated up-regulation of SFRP2 and downregulation of Wnt target genes in airway epithelial cells in vitro. These observations are consistent with the hypothesis that the Wnt pathway plays a role in airway epithelial cell differentiation in the adult human airway epithelium, with smoking associated with down-regulation of Wnt pathway, contributing to the dysregulation of airway epithelial differentiation observed in the smoking-related airway disorders. Affymetrix arrays were used...
putative tumor-promoting properties such as MMP7, VEGFA, and IL-8. In conclusion, synergistic effects between EGFR and HH signaling can selectively induce a switch from a canonical HH/GLI profile to a modulated specific target gene profile pointing to more wide-spread, yet context-dependent, interactions between HH/GLI and growth factor receptor signaling in human malignancies. To study interactions between HH- and EGF-induced signaling, time-resolved measurements were carried out over a period of 24 h at 14 different time points after stimulation by EGF with and without additional stimulation by SHH. Furthermore, as a control, cells without any stimulation by EGF and SHH (control) and cells in the presents of SHH were analyzed. Overall, three biological replicates of 60 different treatment/timepoints were analyzed yielding 180 different samples....
th suppression of pro-angiogenic molecules HIF1a, VEGFa, IL-8 and TGFb1, and with inhibition of tumor angiogenesis. These results provide a proof of principle supporting the rationale for combinatorial treatments with synergistic anti-melanoma activity based on direct and indirect anti-tumor effects. The human melanoma cell line Me13 was established in our laboratory from a surgical specimen. Cells were routinely maintained in RPMI medium 1640 (Lonza, Basel, Switzerland) supplemented with 10% FBS (Lonza) and 2 mM glutamine (Lonza). Cells were maintained at 37°C in a water-saturated atmosphere of 5% CO2 in air. 3x10^6 cells were seeded in 75 cm2 flasks; after 24 hours, cells were left untreated or treated with Selumetinib (Selleck Chemicals, Houston, TX) at 0.1 micromol/L, NVP-BEZ-235 (Selleck Chemicals, Houston, TX) at 0.1 micromol/L and sTRAIL (AdipoGen) at 25ng/ml as single drugs or in combination for 8 hours. Each treatment or combination was performed in triplicate. At the end of treatment, cells were collected and RNA extracted....
Chiang, D. Y. et al. Focal gains of VEGFA and molecular classification of hepatocellular carcinoma. Cancer Res 68, 6779-6788 (2008).
Demichelis, F. et al. Distinct genomic aberrations associated with ERG rearranged prostate cancer. Genes Chromosomes Cancer 48, 366-380 (2009).
Firestein, R. et al. CDK8 is a colorectal cancer oncogene that regulates [bgr]-catenin activity. Nature 455, 547-551 (2008).
George, R. E. et al. Genome-wide analysis of neuroblastomas using high-density single nucleotide polymorphism arrays. PLoS ONE 2, e255 (2007).
GlaxoSmithKline. GSK Cancer Cell Line Genomic Profiling Data, https://cabig.nci.nih.gov/tools/caArray_GSKdata (2008).
Haverty, P. M. et al. High-resolution genomic and expression analyses of copy number alterations in breast tumors. Genes Chromosomes Cancer 47, 530-542 (2008).
Kilpivaara, O. et al. A germline JAK2 SNP is associated with predisposition to the development of JAK2(V617F)-positive myeloproliferative neoplasms. Nat Genet 41, 455-459 (2009).
Lin, W. M. et al. Modeling genomic diversity and tumor dependency in malignant melanoma. Cancer Res 68, 664-673 (2008).
Mullighan, C. G. et al. Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia. Nature 446, 758-764 (2007).
Mullighan, C. G. et al. BCR-ABL1 lymphoblastic leukaemia is characterized by the deletion of Ikaros. Nature 453, 110-114 (2008).
Nikolsky, Y. et al. Genome-wide functional synergy between amplified and mutated genes in human breast cancer. Cancer Res 68, 9532-9540 (2008).
Ramos, A. et al. Amplification of PDGFRA and KIT in Non-small Cell Lung Cancer. Cancer Biology and Therapy 8, 2051-3 (2009).
Sos, M. L. et al. Predicting drug activity in non-small cell lung cancer based on genetic lesions. JCI 119, 1727-1740 (2009).
Weir, B. A. et al. Characterizing the cancer genome in lung adenocarcinoma. Nature 450, 893-898 (2007)....
02 and 0.02) and the EPAS1 downstream target gene VEGFA (p-value = 0.03 and 0.01). The EPAS1 siRNA signatures derived from human and mouse cell lines were highly consistent, with 695 genes in common to both signatures (p-value = 7.2x10-65). Both signatures not only significantly overlapped with EPAS1 downstream genes (p-value = 7.3x10-7 and 1.5x10-12), but also with hypoxia response genes in endothelial cells (Fisher’s Exact Test p-value = 5.8x10-8 and 1.2x10-12 in the human and mouse signatures, respectively). Moreover, the EPAS1 siRNA signatures consistently overlapped genes associated with the COPD severity phenotypes. These results together validate that EPAS1 causally regulates the downstream target genes we predicted, and that these genes in turn affect COPD development and progression. For each of human and mouse cell lines, 3 siRNA control cells, and 3 siRNA EPAS1 knockdown cells were used and analyzed. To identify EPAS1 signatures, paired t-test was performed between control siRNA and EPAS1 siRNA samples....