| Project/Area Number |
08407032
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Kagoshima University |
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Principal Investigator |
TAKAO Sonshin Kagoshima University, 1st Dept. of Surgery, Associate Professor, 医学部, 助教授 (80171411)
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| Co-Investigator(Kenkyū-buntansha) |
OZAWA Masayuki Kagoshima University, 2nd Dept. of Chemistry, Professor, 医学部, 教授 (90136854)
AKIYAMA Shin-ichi Kagoshima University, Cancer Institution, Professor, 医学部, 教授 (60117413)
MURATA Fusayoshi Kagoshima University, 2nd Dept. of Anatomy, Professor, 医学部, 教授 (60020765)
AIKOU Takashi Kagoshima University, 1st Dept. of Surgery, Professor, 医学部, 教授 (60117471)
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| Project Period (FY) |
1996 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥38,900,000 (Direct Cost: ¥38,900,000)
Fiscal Year 1999: ¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 1998: ¥7,300,000 (Direct Cost: ¥7,300,000)
Fiscal Year 1997: ¥12,900,000 (Direct Cost: ¥12,900,000)
Fiscal Year 1996: ¥12,300,000 (Direct Cost: ¥12,300,000)
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| Keywords | carcinoma of digestive organs / invasion / metastasis / thymidine phosphorylase / angiogenesis / micrometastasis / adhesion molecule / IL-1a / E-カドヘリン / 血管新生 / 細胞間相互作用 / 内皮細胞 / Eーカドへリン / カドヘリン-カテニン / アンチセンス / PCR / ヌードマウス / 基底膜浸潤 / 肝転移 / E-カドヘリン・カテニン / クッパー細胞 |
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| Research Abstract |
Thymidine phosphorylase (TP) is identical to PD-ECGF which stimulates chemotaxis of endothelial cells in vitro and has an angiogenic activity in vivo. The expression of TP in primary tumor is associated with a poor prognosis of the patients with carcinoma of the digestive organs. TP can confer resistance to apoptosis induced by hypoxia and the degradation products of thymidine are involved in this resistance. We developed a novel inhibitor of thymidine phosphorylase (TPI). TPI inhabited the high chemotactic motility and basement membrane invasion of KB/TP cells, a TP-positive clone transfected with RSV/TP, to the levels of KB/CV cells, a control clone transfected with RSV. These findings demonstrate that TP plays a key role in invasiveness and metastasis of TP-expressing solid tumors. In nude mice, oral administration of TPI suppressed not only macroscopic liver metastases of highly metastasizing KB/TP cells but also the level of human b-globin as a molecular marker of micrometastases in the livers of the mice. TPI might be a novel anti-metastatic agent for blood-borne metastasis.
The differences between six human pancreatic cancer cell lines were founded in not only expressions of sialyl Lewis antigens but also inducibilities of ELAM-1 expression on endothelial cells. Carcinoma-derived IL-1α play an important role in adhesion mechanism between endothelium and metastasizing cancer cells with sLeィイD1aィエD1 expression.
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