RGD Reference Report - Cooperative stimulation of vascular endothelial growth factor expression by hypoxia and reactive oxygen species: the effect of targeting vascular endothelial growth factor and oxidative stress in an orthotopic xenograft model of bladder carcinoma.

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Cooperative stimulation of vascular endothelial growth factor expression by hypoxia and reactive oxygen species: the effect of targeting vascular endothelial growth factor and oxidative stress in an orthotopic xenograft model of bladder carcinoma.
Authors:	Brown, NS Streeter, EH Jones, A Harris, AL Bicknell, R
Citation:	Brown NS, etal., Br J Cancer. 2005 May 9;92(9):1696-701.
RGD ID:	2293720
Pubmed:	PMID:15841086 (View Abstract at PubMed)
PMCID:	PMC2362032 (View Article at PubMed Central)
DOI:	DOI:10.1038/sj.bjc.6602522 (Journal Full-text)
Elevated thymidine phosphorylase has been shown to correlate with increased angiogenesis and poor prognosis in many cancers including transitional cell carcinoma of the bladder. In vitro studies have demonstrated that thymidine phosphorylase activity causes cellular oxidative stress and increases secretion of vascular endothelial growth factor. In this study, we show that thymidine phosphorylase activity also augments levels of the hypoxia-inducible factor-1alpha during in vitro hypoxia, and that thymidine phosphorylase activity and hypoxia act in concert to increase vascular endothelial growth factor (VEGF) secretion. We also demonstrate that thymidine phosphorylase overexpression confers tumorigenicity on an orthotopically implanted transitional cell carcinoma cell line. Administration of the antioxidant N-acetylcysteine together with a blocking anti-VEGF antibody abrogates the increase in tumorigenicity. Our results support the increased efficacy of combination approaches to antiangiogenic therapy.

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
TYMP	Human	transitional cell carcinoma		IMP			RGD
Tymp	Rat	transitional cell carcinoma		ISO	TYMP (Homo sapiens)		RGD
Tymp	Mouse	transitional cell carcinoma		ISO	TYMP (Homo sapiens)		RGD

Objects Annotated

Genes (Rattus norvegicus)

Tymp (thymidine phosphorylase)

Genes (Mus musculus)

Tymp (thymidine phosphorylase)

Genes (Homo sapiens)

TYMP (thymidine phosphorylase)

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Cooperative stimulation of vascular endothelial growth factor expression by hypoxia and reactive oxygen species: the effect of targeting vascular endothelial growth factor and oxidative stress in an orthotopic xenograft model of bladder carcinoma.