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Abstract

Abstract: Inhibition of tumor angiogenesis-the growth of new blood vessels towards the tumor mass-is a new and promising approach to anti-cancer therapy. The results of Phase I/II clinical trials completed so far with several angiogenesis inhibitors validate the concept of tumor angiogenesis as effective target for anti-cancer therapy. However, the same studies stress the need for novel, more potent angiogenesis inhibitors. We addressed this need by isolating the human urine a new protein (SBD.1), which specifically blocks the proliferation of capillary endothelial cells in vitro (ID50=15NG/ML), angiogenesis in chorioallentoic membrane assay, and two growth in vivo (Lewis Lung Carcinoma, T/C=0.04 at 20umum/kg/day), placing SBD.1 among the most potent known angiogenesis inhibitors. Sequencing of SBD/1 showed it is a novel protein and its mild proteolysis resulted in the generation of smaller peptides without losing the inhibitory activity. Here, we propose to a) clone and express SBD.1 in a recombinant system; b) isolate and sequence the activity SBD.1 fragments; c) test the purified SBD.1 on prostate, lung and breast carcinoma human xenografts in nude mice to further assess its anti-tumor activity This project will result in the cloning of a novel therapeutically-active protein, which may be an important endogenous regulator of angio- and tumorigenesis in humans. PROPOSED COMMERCIAL APPLICATIONS: The development of SBD.1 addresses a pressing need in the pharmaceutical industry for a new, better angiogenesis inhibitor. Currently targeting anti-cancer therapy, the use of SBD.1 might be later extended to the treatment of vascular pathologies, such as macular degeneration and certain cardiovascular diseases. Meanwhile, SBD.1 can also be commercialized as reagent for laboratory research on angiogenesis. Taken together, these applications represent a substantial potential market for SBD.1

Thesaurus Terms:
angiogenesis inhibitor, antineoplastic, drug design /synthesis /production, drug screening /evaluation, neoplasm /cancer blood supply, protein sequence, protein structure function
breast neoplasm, lung neoplasm, prostate neoplasm
athymic mouse, clinical research, human tissue, molecular cloning, protein purification

Institution:	SUNNY BIODISCOVERY
	675 HEGENBERGER RD, 2ND FL
	OAKLAND, CA 94601
Fiscal Year:	2002
Department:
Project Start:	01-JUN-2002
Project End:	30-MAY-2003
ICD:	NATIONAL CANCER INSTITUTE
IRG:	ZCA1