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To: tnsaf who wrote (1488)	2/10/2002 6:54:03 PM
From: tnsaf	Respond to of 7143

Targeting the prostate for destruction through a vascular address Proc. Natl. Acad. Sci. USA, Vol. 99, Issue 3, 1527-1531, February 5, 2002 Wadih Arap,,, Wolfgang Haedicke,,§, Michele Bernasconi, Renate Kain¶,, Daniel Rajotte,*, Stanislaw Krajewski, H. Michael Ellerby,, Dale E. Bredesen,, Renata Pasqualini,, and Erkki Ruoslahti, Organ specific drug targeting was explored in mice as a possible alternative to surgery to treat prostate diseases. Peptides that specifically recognize the vasculature in the prostate were identified from phage-displayed peptide libraries by selecting for phage capable of homing into the prostate after an i.v. injection. One of the phage selected in this manner homed to the prostate 10-15 times more than to other organs. Unselected phage did not show this preference. The phage bound also to vasculature in the human prostate. The peptide displayed by the prostate-homing phage, SMSIARL (single letter code), was synthesized and shown to inhibit the homing of the phage when co-injected into mice with the phage. Systemic treatment of mice with a chimeric peptide consisting of the SMSIARL homing peptide, linked to a proapoptotic peptide that disrupts mitochondrial membranes, caused tissue destruction in the prostate, but not in other organs. The chimeric peptide delayed the development of the cancers in prostate cancer-prone transgenic mice (TRAMP mice). These results suggest that it may be possible to develop an alternative to surgical prostate resection and that such a treatment may also reduce future cancer risk. ------------------------------------------------------------ www.pnas.org/cgi/doi/10.1073/pnas.241655998