US EPA

7431834 

Journal Article 

Antitumor effects of angiogenesis inhibitor TNP-470 in rabbits bearing VX-2 carcinoma by arterial administration of microspheres and oil solution 

Kamei, S; Okada, H; Inoue, Y; Yoshioka, T; Ogawa, Y; Toguchi, H; , 

1993 

Yes 

Journal of Pharmacology and Experimental Therapeutics
ISSN: 0022-3565
EISSN: 1521-0103 

WILLIAMS & WILKINS 

BALTIMORE 

264 

1 

469-474 

English 

7678651 

WOS:A1993KG48400066 

The antitumor activities of an angiogenesis inhibitor, (3R,4S,5S,6R)-5- methoxy-4-[(2R,3R)-2-methyl-3-(3-methyl-2-butenyl)-oxiranyl]-1- oxaspiro[2,5]oct-6-yl(chloroacetyl) carbamate (TNP-470), administered s.c., i.v. and intra-arterially using a chemoembolization technique, were examined in rabbits bearing VX-2 carcinoma. Repeated s.c. injection of TNP-470 aqueous solution clearly inhibited the tumor growth in proportion to the dose, and improved efficacy was obtained with once a week s.c. administration of microspheres, which provide sustained release of TNP-470. Moreover, the injection of the TNP-470 microspheres into the predominant artery of the tumor via a catheter, chemoembolization, resulted in dramatic regression of the tumor. This antitumor effect was enhanced by coadministration of doxorubicin hydrochloride aqueous solution. Arterial administration of TNP-470 oil solution provided more persistent tumor growth inhibition due to the prolonged release and targeting of the angiogenesis inhibitor to the tumor. 

antineoplastic agent; doxorubicin; fumagillol chloroacetylcarbamate; microsphere; angiogenesis; animal experiment; animal model; antineoplastic activity; article; artificial embolism; cancer inhibition; carcinoma; controlled study; dose response; drug efficacy; drug structure; intraarterial drug administration; intravenous drug administration; male; nonhuman; priority journal; rabbit; subcutaneous drug administration; tumor volume; Animal; Antibiotics, Antineoplastic; Carcinoma; Disease Models, Animal; Doxorubicin; Female; Injections, Intra-Arterial; Injections, Intravenous; Injections, Subcutaneous; Iodized Oil; Male; Microspheres; Neoplasm Transplantation; Neoplasms, Experimental; Neovascularization, Pathologic; Rabbits; Sesquiterpenes; Solutions