Effects of 5-(2-chlorobenzyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine hydrochloride (Ticlopidine), a platelet aggregation inhibitor, on blood-borne metastasis.

A new platelet aggregation inhibitor compound, 5-(2-chlorobenzyl-4,5,6,7-tetrahydrothieno[3,2-C]pyridine hydrochloride (ticlopidine), was examined for its inhibitory effects on blood-borne metastasis using three different rodent tumors (B16 melanoma, Lewis lung carcinoma, and rat ascites hepatoma, AH130). Ticlopidine was administered p.o. to the rodents. It inhibited the aggregation of platelets induced by adenosine diphosphate, thrombin, crude extract of AH130, and viable AH130 and B16 melanoma cells and also resulted in a significant decrease of pulmonary metastasis induced by i.v. injection of B16 melanoma and AH130. Spontaneous pulmonary metastasis of Lewis lung carcinoma was also inhibited by p.o. administration of ticlopidine. This new compound may be a useful agent for inhibiting platelet aggregation caused by various agents and for suppressing hematogenous pulmonary metastasis.

Studies on platelet aggregation in vivo. VII: Effect of pentoxyfylline on circulating tumor cells.

Pentoxifylline, a platelet aggregation inhibitor, increased circulation time of intravenously injected, labeled tumor cells in male mice.

Decrease in experimental liver metastasis in mice after treatment with pyran copolymer.

Intravenous injection of pyran copolymer (divinyl ether-maleic anhydride) 24 h prior to intravenous injection of B16 melanoma in C57/BL6 mice greatly decreased the number of liver metastases. If the pyran copolymer was administered 3 days after injection of tumor cells, the number of metastases was not significantly decreased. Pyran copolymer has been reported to stimulate interferon production and increase clearance of particulate matter by the reticuloendothelial system. The results of this experiment suggests an important role played by the reticuloendothelial system in experimental liver metastasis.