1995 Fiscal Year Final Research Report Summary
The effects of Thymidine phsphorylase on tumor angiogenesis and on the sensitivity to anti-tumor drugs
| Project/Area Number |
06670172
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Kagoshima University |
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Principal Investigator |
HARAGUCHI Misako Faculty of Medicine, Research Associate Kagoshima University, 医学部, 助手 (10244229)
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| Co-Investigator(Kenkyū-buntansha) |
AKIYAMA Sinichi Faculty of Medicine Professor Kagoshima University, 医学部, 教授 (60117413)
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| Project Period (FY) |
1994 – 1995
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| Keywords | Tymidine phosphorylase / Angiogenesis / The sensitivity to anti-tumor drugs / Chick embryo chorioallantoic membrane assay / Chemtaxis |
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| Research Abstract |
Human thymidine phsphorylase (dThdPase) is thought to be indentical to an angiogenic factor, Platelet-derived endothelial cell growth factor (PD-ECGF) .However, the whole amino acid sequence of dThdPase is still unknown. N-termina amino acid sequencing of dThdPase isolated human placenta gave the sequence Ac-AALMTPGTGAPPAPG.Comparison with the sequence predicted from the PD-ECGFcDNA reveals that residues 2-16 of dThdPase are indentical to that of PD-ECGF.The primary translational product of dThdPase would be processed one amino acid from the translation-initiating methionine residue and Ala-2 acetylated.
dThdPase has angiogenic activity. To investigate whether the dThdpase activity of PD-ECGF/dThdpase is indispensable to its angiogenic activity, three PD-ECGF/dThdpase mutant which have no dThdpase activity were made by site-derected mutagenesis. The lysates of COS cells transfected with the wild-type PD-ECGF/dThdpase cDNA had angiogenic activity, but those transfected with the mutant PD-ECGF/dThdpase did not. An inhibitor of dThdpase, 6-amino-5-chlorouracil, inhibited the angiogenic activity of purified dThdPase. These findings indicate that dThdpase activity is indispensable to angiogenic activity of PD-ECGF/dThdpase.
Human KB epidermal carcinoma cells transfected with PD-ECGF cDNA expressed a 55-kDa protein that was detected with anti-dThdPase antibody and the cell lysate had dThdPase activity. The sensitivity of the transfected cells to 5'-deoxy-5-fluorouridine was higher than that of untransfected KB cells. These results demonstrate that dThdPase is involved in the activation of these anticancer agents.
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Research Products
(12 results)
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[Publications] Miyadera,K., Sumizawa,T., Haraguchi,M., Yoshida,H., Konstanty,W., Yamada,Y. and Akiyama,S.: "Role of thymidine phosphorylase activity in the angiogenic effect of platelet-derived endothelial cell growth factor/thymidine phosphorylase." Cancer Res.55. 1687-1690 (1995)
Description
「研究成果報告書概要(和文)」より
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[Publications] Miyadera,K., Dohmac,N., Takio,K., Sumizawa,T., Haraguchi,M., Furukawa,T., Yamada,Y. and Akiyama,S.: "Structural characterization of thymidine phosphorylase purified from human placenta." Biochem. Biophys. Res. Commun.212. 1040-1045 (1995)
Description
「研究成果報告書概要(和文)」より
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[Publications] Haraguchi,M., Miyadera,K., Uemura,K., Sumizawa,T., Furuakawa,T., Yamada,Y., Yamada,K., and Akiyama,S.: "Angiogenic activiyty of Enzymes." Nature. 368. 198- (1994)
Description
「研究成果報告書概要(和文)」より
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[Publications] Chuman;Y., Sumizawa,T., Takebayashi,Y., Niwa,K., Yamada,K., Haraguchi,M., Furukawa,T., Akiyama,S. and Aikou,T.: "Expression of the multidrug-resisitance-associated protein (MRP) gene in human colorectal, gastric and non-small-cell lung carcinomas." Int. J. Cancer. 65. 1-6 (1996)
Description
「研究成果報告書概要(和文)」より
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[Publications] Miyadera, K., Sumizawa, T., Haraguchi, M., Yochida, H., Konstanty, W., Yamada, Y.and Akiyama, S.: "Role of thymidine phosphorylase activity in the angiogenic effect of platelet-derived endothelial cell growth factor/thymidine phosphorylase." Cancer Res.55. 1687-1690 (1995)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Miyadera, K., Dohmae, N., Takio, K., Sumizawa, T., Haraguchi, M., Furukawa, T., Yamada, Y.and Akiyama, S.: "Structural characterization of thymidine phosphorylase purified from human placenta." Biochem.Biophys.Res.Commun.212. 1040-1045 (1995)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Haraguchi, M., Miyadera, K., Uemura, K., Sumizawa, T., Furuakawa, T., Yamada, Y., Yamada, K., and Akiyama, S.: "Angiogenic activiyty of Enzymes." Nature. 368. 198 (1994)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Chuman, Y., Sumizawa, T., Takebayashi, Y., Niwa, K., Yamada, K., Haraguchi, M., Furukawa, T., Akiyama, S.and Aikou, T.: "Expression of the multidrug-resisitance-associated protein (MRP) gene in human colorectal, gastric and non-small-cell lung carcinomas." Int.J.Cancer. 65. 1-6 (1996)
Description
「研究成果報告書概要(欧文)」より
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