@misc{oai:ir.kagoshima-u.ac.jp:00010758, author = {松下, 茂人 and Matsushita, Shigeto}, month = {}, note = {Thymidine phosphorylase (TP) is an enzyme involved in the reversible conversion of thymidine to thymine, and is identical to an angiogenic factor, platelet-derived endothelial cell growth factor (PD-ECGF). TP is expressed at higher levels in a wide variety of solid tumors than in the adjacent non-neoplastic tissues. Patients with TP-positive colon and esophageal tumors have a poorer prognosis than those with negative tumors. We have recently synthesized a new TP inhibitor (TPI), 5-chloro-6-[1-(2-iminopyrrolidinyl) methyl] uracil hydrochloride. We investigated the effect of TPI on angiogenesis by KB cells transfected with PD-ECGF cDNA, KB/TP, and a mock transfectant, KB/CV, using the mouse dorsal air sac assay model. We found that KB/TP had higher angiogenic ability than KB/CV, and TPI completely suppressed angiogenesis by KB/TP. Furthermore, TPI, at a dose of 50 mg/kg/day, considerably decreased the growth rate of KB/TP xenografted into nude mice. Microvessel density in KB/TP tumors was higher than in KB/CV tumors and TPI did not significantly change the density in both tumors. The apoptotic index in KB/TP tumors was significantly lower than in KB/CV tumors, and TPI significantly increased the apoptotic index in KB/TP but not in KB/CV tumors. These findings, taken together with previous reports, suggest that expression of TP plays an important role in tumor growth, and that the inhibitor of TP, TPI, su ppresses tumor growth by increasing the proportion of apoptotic cells and probably inhibiting angiogenesis., 医歯学総合研究科博士論文(医学) ; 学位取得日: 平成11年4月28日}, title = {The Effect of a Thymidine Phosphorylase Inhibitor on Angiogenesis and Apoptosis in Tumors}, year = {1999}, yomi = {マツシタ, シゲト} }