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- W4361949062 abstract "<div>Abstract<p><b>Purpose:</b> Tumors produce multiple proangiogenic factors, making it unlikely that agents targeting a single angiogenic pathway will be sufficient to treat the spectrum of tumors that occur clinically. Platelet-derived endothelial cell growth factor has angiogenic activity <i>in vitro</i> and <i>in vivo</i> and is overexpressed in most human cancers, where its expression has been correlated with increased microvessel density, more aggressive tumors, and poorer patient prognosis. Platelet-derived endothelial cell growth factor is identical to the enzyme thymidine phosphorylase (TP), and unlike other angiogenic factors, the proangiogenic actions of TP are dependent on its enzyme activity.</p><p><b>Experimental Design:</b> A potent and specific small-molecule inhibitor of the catalytic activity of TP, 6-(2-aminoethyl)amino-5-chlorouracil (AEAC), was tested for antiangiogenic and antitumor activity in human cancer xenografts <i>in vivo</i>.</p><p><b>Results:</b> Oral administration of AEAC caused 40% to 50% reductions in the growth of A549 non–small cell lung cancer and PANC-1 pancreatic cancer xenografts, but it was not active against a second pancreatic tumor, BxPC-3. AEAC reduced the microvessel density in the tumors, providing evidence for an antiangiogenic action. Equal or better activity was seen when the mice were treated with the vascular endothelial growth factor (VEGF)-Trap, a soluble VEGF decoy receptor, and the combination of AEAC and VEGF-Trap produced additive antitumor activity that was significantly greater than the VEGF-Trap alone. In the A549 tumors, the combination produced tumor regressions.</p><p><b>Conclusion:</b> These studies show antitumor activity for a drug targeting TP and suggest that inhibitors of TP could be used to augment the clinical efficacy of drugs targeting the VEGF pathway. (Clin Cancer Res 2009;15(16):5136–44)</p></div>" @default.
- W4361949062 created "2023-04-05" @default.
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- W4361949062 date "2023-03-31" @default.
- W4361949062 modified "2023-09-26" @default.
- W4361949062 title "Data from Antiangiogenic and Antitumor Activity of 6-(2-Aminoethyl)Amino-5-Chlorouracil, a Novel Small-Molecule Inhibitor of Thymidine Phosphorylase, in Combination with the Vascular Endothelial Growth Factor-Trap" @default.
- W4361949062 doi "https://doi.org/10.1158/1078-0432.c.6517528.v1" @default.
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