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English Wikipedia
Nephropedia Template TP (
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lüll The role of thymidine phosphorylase, an angiogenic enzyme, in tumor progression Akiyama S; Furukawa T; Sumizawa T; Takebayashi Y; Nakajima Y; Shimaoka S; Haraguchi MCancer Sci 2004[Nov]; 95 (11): 851-7Thymidine phosphorylase (TP), an enzyme involved in pyrimidine metabolism, is identical with an angiogenic factor, platelet-derived endothelial cell growth factor (PD-ECGF). TP is overexpressed in various tumors and plays an important role in angiogenesis, tumor growth, invasion and metastasis. The enzymatic activity of TP is required for the angiogenic effect of TP. A novel, specific TP inhibitor, TPI, inhibits angiogenesis induced by overexpression of TP in KB/TP cells (human KB epidermoid carcinoma cells transfected with TP cDNA), as well as the growth and metastasis of KB/TP cells in vivo. 2-deoxy-D-ribose, the degradation product of thymidine generated by TP activity, has both angiogenic and chemotactic activity. Both 2-deoxy-D-ribose and TP inhibit a hypoxia-induced apoptotic pathway. These findings suggest that 2-deoxy-D-ribose is a downstream mediator of TP function. 2-deoxy-L-ribose, a stereoisomer of 2-deoxy-D-ribose, inhibits the promotion of angiogenesis, tumor growth and metastasis by TP. Although the mechanism of the action of 2-deoxy-D-ribose is still unknown, 2-deoxy-L-ribose may inhibit the physiological activities of 2-deoxy-D-ribose, and consequently those of TP. Inhibition of TP activity and function appears to be a promising approach for the chemotherapy of various tumors.|Angiogenesis Inducing Agents/pharmacology[MESH]|Antigens, CD/metabolism[MESH]|Antigens, Differentiation, Myelomonocytic/metabolism[MESH]|Apoptosis/drug effects[MESH]|Cell Line, Tumor[MESH]|Deoxyribose/metabolism[MESH]|Humans[MESH]|Neoplasm Invasiveness[MESH]|Neoplasm Metastasis[MESH]|Neoplasms/*enzymology[MESH]|Neovascularization, Pathologic/*enzymology[MESH]|Thymidine Phosphorylase/antagonists & inhibitors/*physiology[MESH]|Thymidine/metabolism[MESH] |