| pubmed-article:19240722 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:19240722 | lifeskim:mentions | umls-concept:C0086418 | lld:lifeskim |
| pubmed-article:19240722 | lifeskim:mentions | umls-concept:C0677886 | lld:lifeskim |
| pubmed-article:19240722 | lifeskim:mentions | umls-concept:C0078058 | lld:lifeskim |
| pubmed-article:19240722 | lifeskim:mentions | umls-concept:C0164786 | lld:lifeskim |
| pubmed-article:19240722 | lifeskim:mentions | umls-concept:C1256770 | lld:lifeskim |
| pubmed-article:19240722 | lifeskim:mentions | umls-concept:C0812228 | lld:lifeskim |
| pubmed-article:19240722 | lifeskim:mentions | umls-concept:C1710082 | lld:lifeskim |
| pubmed-article:19240722 | lifeskim:mentions | umls-concept:C1704259 | lld:lifeskim |
| pubmed-article:19240722 | lifeskim:mentions | umls-concept:C1705987 | lld:lifeskim |
| pubmed-article:19240722 | pubmed:issue | 6 | lld:pubmed |
| pubmed-article:19240722 | pubmed:dateCreated | 2009-3-18 | lld:pubmed |
| pubmed-article:19240722 | pubmed:abstractText | Vascular endothelial growth factor (VEGF)-A inhibitors exhibit unseen high responses and toxicity in recurrent epithelial ovarian cancer suggesting an important role for the VEGF/VEGFR pathway. We studied the correlation of VEGF signalling and AKT/mTOR signalling. Using a tissue microarray of clinical samples (N=86), tumour cell immunohistochemical staining of AKT/mTOR downstream targets, pS6 and p4E-BP1, together with tumour cell staining of VEGF-A and pVEGFR2 were semi-quantified. A correlation was found between the marker for VEGFR2 activation (pVEGFR2) and a downstream target of AKT/mTOR signalling (pS6) (R=0.29; P=0.002). Additional gene expression analysis in an independent cDNA microarray dataset (N=24) showed a negative correlation (R=-0.73, P<0.0001) between the RPS6 and the VEGFR2 gene, which is consistent as the gene expression and phosphorylation of S6 is inversely regulated. An activated tumour cell VEGFR2/AKT/mTOR pathway was associated with increased incidence of ascites (chi(2), P=0.002) and reduced overall survival of cisplatin-taxane-based patients with serous histology (N=32, log-rank test, P=0.04). These data propose that VEGF-A signalling acts on tumour cells as a stimulator of the AKT/mTOR pathway. Although VEGF-A inhibitors are classified as anti-angiogenic drugs, these data suggest that the working mechanism has an important additional modality of targeting the tumour cells directly. | lld:pubmed |
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| pubmed-article:19240722 | pubmed:language | eng | lld:pubmed |
| pubmed-article:19240722 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19240722 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:19240722 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:19240722 | pubmed:month | Mar | lld:pubmed |
| pubmed-article:19240722 | pubmed:issn | 1532-1827 | lld:pubmed |
| pubmed-article:19240722 | pubmed:author | pubmed-author:DirixL YLY | lld:pubmed |
| pubmed-article:19240722 | pubmed:author | pubmed-author:van DamP APA | lld:pubmed |
| pubmed-article:19240722 | pubmed:author | pubmed-author:Van der... | lld:pubmed |
| pubmed-article:19240722 | pubmed:author | pubmed-author:VermeulenP... | lld:pubmed |
| pubmed-article:19240722 | pubmed:author | pubmed-author:HellemanJJ | lld:pubmed |
| pubmed-article:19240722 | pubmed:author | pubmed-author:TjalmaW A AWA | lld:pubmed |
| pubmed-article:19240722 | pubmed:author | pubmed-author:BernsE M J... | lld:pubmed |
| pubmed-article:19240722 | pubmed:author | pubmed-author:TrinhX BXB | lld:pubmed |
| pubmed-article:19240722 | pubmed:author | pubmed-author:Van den... | lld:pubmed |
| pubmed-article:19240722 | pubmed:author | pubmed-author:Van LaereS... | lld:pubmed |
| pubmed-article:19240722 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:19240722 | pubmed:day | 24 | lld:pubmed |
| pubmed-article:19240722 | pubmed:volume | 100 | lld:pubmed |
| pubmed-article:19240722 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:19240722 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:19240722 | pubmed:pagination | 971-8 | lld:pubmed |
| pubmed-article:19240722 | pubmed:dateRevised | 2010-11-18 | lld:pubmed |
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