An experimental study to prevent hepatic metastasis at the resection of GI tract cancer -with special referemce to the efficacy of platelet aggregating inhibitor-

Research Project

Project/Area Number	04670793
Research Category	Grant-in-Aid for Scientific Research (C).
Allocation Type	Single-year Grants
Research Field	消化器外科学
Research Institution	Fukushima Medical College
Principal Investigator	HOSHINO Masami Fukushima Medical College, Instructor, 医学部, 講師 (60165545)
Co-Investigator(Kenkyū-buntansha)	INOUE N Fukushima Medical College, Associate, 医学部, 助手 (10223265) URAZUMI K Fukushima Medical College, Associate, 医学部, 助手 (90203603)
Project Period (FY)	1992 – 1993
Project Status	Completed (Fiscal Year 1993)
Budget Amount *help	¥500,000 (Direct Cost: ¥500,000) Fiscal Year 1993: ¥500,000 (Direct Cost: ¥500,000)
Keywords	cancer / metastasis / platelet / Tx-A_2 / PAF antagonist / Tx-A_2 synthetase inhibitor / OKY-046 / TCV-309 / Tx-A_2synthecase inhibitor / 肝転移予防 / 血小板凝集阻害剤 / VX-2腫瘍
Research Abstract	To investigate whether a platelet aggregation inhibitor (OKY-046 (an inhibitor of thromboxane A_2 synthesis) and TCV-309 (an antagonist of platelet aggregating factor) ) can inhibit VX-2 tumor metastasis, following two experimental studies were performed. Study 1 : VX-2 tumor cells (1*10^7cells) were inoculated into the portal vein and OKY-046 at 0.6mg/kg/hour (group A) or TCV-309at 0.8mg/kg/hour (group B) was administered continuously into the portal vein from 30 min. befor tumor cell inoculation through the following 2 days. In group C,adriamycin (ADM) 1mg/kg was administered via the portal vein on the next day, 3rd, and 5th day after OKY-046 infusion was completed. Only ADM was administered into the portal vein on the 3rd, 5th and 7th day in the group D and immediately and on the 2nd and 4th day after tumor cell inoculation in group E.The numbers of tumor nodules on the whole liver surface at three weeks after tumor inoculation in the controll, group A,B,C,D,and E were 541.6<plus-min … More us>79.0,438.8<plus-minus>59.5,570.0<plus-minus>35.0,8<plus-minus>6.1,130.0<plus-minus>89.7 and 9.5<plus-minus>5.3 respecti Study 2 : At 72 hours after MCF-7, human breast cancer cells, were overlayd on confluently cultured human endothelial cells, MCF-7 cells invaded through the endothelial cells and built up the colony under human endothelial cells. The number of the colonys was referred to the invasion activity of MCF7 cells. To investigate the mechanisms why OKY-046 inhibits the extravasation of the VX-2 tumor cells inoculated into the portal vein, MCF-7 cells were overlayd on human endothelial cells and culturld with the medium containing various concentrations of OKY-046 or TCV-309. OKY-046 significantly decreased the number of the colonys of MCF-7 cells under the human endothelial cells directly proportional to the concentration of OKY-046 in the medium, but TCV-309 did not show this activity. These results suggest that the inhibitory effect of the tumor growth of OKY-046 depend on inhibition of extravasation of the portally inoculated VX-2 tumor cells. Less