1999 Fiscal Year Annual Research Report

チミジンホスホリラーゼの生理機能と腫瘍増殖への関与の機構

Research Project

Project/Area Number	10470043
Research Institution	Kagoshima University
Principal Investigator	秋山伸一鹿児島大学, 医学部, 教授 (60117413)
Co-Investigator(Kenkyū-buntansha)	谷綾子鹿児島大学, 医学部, 助手 (70284867) 住澤知之鹿児島大学, 医学部, 助手 (90206582) 古川龍彦鹿児島大学, 医学部, 助手 (40219100) 小松正治鹿児島大学, 医学部, 講師研究機関研究員
Keywords	チミジンホスホリラーゼ / ノックアウトマウス / 血管新生 / 低酸素 / アトポーシス / デオキシリボース / PD-ECGF / チトクロームC
Research Abstract	1、チミジンホスホリラーゼ(TP)の生理機能を調べるために、TP遺伝子のノックアウトマウスを作成し、病態を解析しようとしているが、現在ジャームラインキメラマウスを作成した段階である。今後、ジャームラインキメラマウスを交配してノックアウトマウスを作成し、病態を調べることによりTPの生理機能を解析する予定である。 2、TPのアポトーシスへの関与を調べた。TPは血管新生以外に低酸素で誘導されるアポトーシスに対して細胞に耐性を賦与することが判明した。TPによるチミジン分解産物中2-deoxy-D-riboseが血管新生活性を有し、低酸素で誘導されるアポトーシスに耐性を賦与した。2-deoxy-L-ribosは、2-deoxy-D-rioseによるこの耐性賦与を阻害した。低酸素下ではHIF-1αの発現が増加し、Bcl-2、BcL-XLの発現レベルが低下するが、2-deoxy-D-ribosはそれらの反応を抑制した。 3、TPの腫瘍増殖、浸潤、転移への関与を調べた。TPcDNAをトランスフェクトしTPを高発現したKB/TP細胞は、TPを発現していないKB/CV細胞に比べ、浸潤能、走化性が亢進していた。両細胞をヌードマウスに移植したとき、KB/TP細胞の血管新生、増殖能、転移能は、KB/CV細胞に比べ高く、アポトーシス細胞比率は低かった。TPの阻害剤であるTPIは、TPによるこれらの働きを抑制することにより腫瘍の増殖、転移を抑制していることが示唆された。

Research Products
(16 results)

All Other

All Publications (16 results)

[Publications] Takabayashi,Y.,: "Thymidine phosphorylase in human esophageal squamous cell carcinoma."Cancer. 85. 282-289 (1999)
[Publications] Chu,X.-Y.,: "Active efflux of CPT-11 and its metabolites in human KB-derived cell lines."J.Pharmacol.Exp.Ther.,. 288. 753-741 (1999)
[Publications] Fukuiwa,T.,: "Expression of thymidine phosphorylase and vascular endothelial cell growth factor in human head and neck squamous cell carcinoma and their different characteristids."Cancer. 85. 960-969 (1999)
[Publications] Fukuda,S.,: "Expression of vascular endothelial growth factor (VEGF) in testicular germ cell tumors as an indicator of metastatic disease."Cancer. 85. 1323-1330 (1999)
[Publications] Chen,Z.-S.,: "An enhanced active efflux of CPT-11 and SN-38 in cisplatin-resistant human KB carcinoma cells."Cencer Lett.,. 138. 13-22 (1999)
[Publications] Ueda,K.,: "Differences in substrate specificity among GS-X,pump family.members:Comparison between MRP and a novel transporter expressed on a cisplatin-resistant cell line(KOP-4)"Jpn.J.Cancer Res.,. 90. 439-447 (1999)
[Publications] Matsushita,S.,: "The effect of a thymidine phosphorylase inhibitor on angiogenesis and apoptosis in tumors."Cancer Res.,. 59. 1911-1961 (1999)
[Publications] Chen,Z.S.,: "ATP-dependent efflux of CPT-11 and SN-38 by the multidrug resistance protein (MRP) and its inhibition by PAK-104P."Mol.Pharmacol.. 55. 921-928 (1999)
[Publications] Kitazono,M.,: "Multidrug resistance and the lung resistance-related protein in human colon carcinoma SW-620 cells."J.Natl.Cancer Inst.,. 91. 1647-1653 (1999)
[Publications] Chen,Z-S.,: "Effect of multidrug resistance reversing agents on the teansporting activity of human canalicular multispecific organic anino transporter (cMOAT)."Mol.Pharmacol.,. 56. 1219-1228 (1999)
[Publications] Aoki,S.,: "Reversal of multidrug resistance in human carcinoma cell line by agosterols,marine spongean sterols."Tetrahedron,. 55. 13965-13972 (1999)
[Publications] Kawabe,T.,: "Enhanced transport of anticancer agents and leukotriene C4 by the human canalicular multispecific organic anion transporter."FEBS Lett.,. 465. 327-331 (1999)
[Publications] Dendritic Cells: "Immunohistochemical analysis of thymidine phosphorylase overexpression in malignant lymphomas (ML),especially in adult T-cell leukemia/lymphoma (ATLL)."Hasui,K.,. 9. 15-25 (1999)
[Publications] Arima,J.,: "Expression of thymidine phosphorylase as an indicator of poor prognosis in human transitional cell carcinoma."Cancer. (in press).
[Publications] Shimaoka,S.,: "Role of thymidine phosphorylase expression in the invasion of gastric carcinomas."Cancer. (in press).
[Publications] Komatsu,M.,: "Copper transporting P-type ATPase (ATP7B) is associated with cisplatin resistance."Cancer Res.. (in press).

1999 Fiscal Year Annual Research Report

チミジンホスホリラーゼの生理機能と腫瘍増殖への関与の機構

Principal Investigator

秋山 伸一 鹿児島大学, 医学部, 教授 (60117413)

Research Products

[Publications] Takabayashi,Y.,: "Thymidine phosphorylase in human esophageal squamous cell carcinoma."Cancer. 85. 282-289 (1999)

[Publications] Chu,X.-Y.,: "Active efflux of CPT-11 and its metabolites in human KB-derived cell lines."J.Pharmacol.Exp.Ther.,. 288. 753-741 (1999)

[Publications] Fukuiwa,T.,: "Expression of thymidine phosphorylase and vascular endothelial cell growth factor in human head and neck squamous cell carcinoma and their different characteristids."Cancer. 85. 960-969 (1999)

[Publications] Fukuda,S.,: "Expression of vascular endothelial growth factor (VEGF) in testicular germ cell tumors as an indicator of metastatic disease."Cancer. 85. 1323-1330 (1999)

[Publications] Chen,Z.-S.,: "An enhanced active efflux of CPT-11 and SN-38 in cisplatin-resistant human KB carcinoma cells."Cencer Lett.,. 138. 13-22 (1999)

[Publications] Ueda,K.,: "Differences in substrate specificity among GS-X,pump family.members:Comparison between MRP and a novel transporter expressed on a cisplatin-resistant cell line(KOP-4)"Jpn.J.Cancer Res.,. 90. 439-447 (1999)

[Publications] Matsushita,S.,: "The effect of a thymidine phosphorylase inhibitor on angiogenesis and apoptosis in tumors."Cancer Res.,. 59. 1911-1961 (1999)

[Publications] Chen,Z.S.,: "ATP-dependent efflux of CPT-11 and SN-38 by the multidrug resistance protein (MRP) and its inhibition by PAK-104P."Mol.Pharmacol.. 55. 921-928 (1999)

[Publications] Kitazono,M.,: "Multidrug resistance and the lung resistance-related protein in human colon carcinoma SW-620 cells."J.Natl.Cancer Inst.,. 91. 1647-1653 (1999)

[Publications] Chen,Z-S.,: "Effect of multidrug resistance reversing agents on the teansporting activity of human canalicular multispecific organic anino transporter (cMOAT)."Mol.Pharmacol.,. 56. 1219-1228 (1999)

[Publications] Aoki,S.,: "Reversal of multidrug resistance in human carcinoma cell line by agosterols,marine spongean sterols."Tetrahedron,. 55. 13965-13972 (1999)

[Publications] Kawabe,T.,: "Enhanced transport of anticancer agents and leukotriene C4 by the human canalicular multispecific organic anion transporter."FEBS Lett.,. 465. 327-331 (1999)

[Publications] Dendritic Cells: "Immunohistochemical analysis of thymidine phosphorylase overexpression in malignant lymphomas (ML),especially in adult T-cell leukemia/lymphoma (ATLL)."Hasui,K.,. 9. 15-25 (1999)

[Publications] Arima,J.,: "Expression of thymidine phosphorylase as an indicator of poor prognosis in human transitional cell carcinoma."Cancer. (in press).

[Publications] Shimaoka,S.,: "Role of thymidine phosphorylase expression in the invasion of gastric carcinomas."Cancer. (in press).

[Publications] Komatsu,M.,: "Copper transporting P-type ATPase (ATP7B) is associated with cisplatin resistance."Cancer Res.. (in press).

秋山伸一鹿児島大学, 医学部, 教授 (60117413)