{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T18:32:10Z","timestamp":1761762730004},"reference-count":43,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2005,7,7]],"date-time":"2005-07-07T00:00:00Z","timestamp":1120694400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2006,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We developed a powerful cytotoxic analogue of bombesin AN\u2010215, in which the bombesin (BN)\u2010like carrier peptide is conjugated to 2\u2010pyrrolino doxorubicin (AN\u2010201). Human prostate cancers express high levels of receptors for BN\/gastrin releasing peptide (GRP) that can be used for targeted chemotherapy. The effects of targeted chemotherapy with cytotoxic BN analogue AN\u2010215 were evaluated in nude mice bearing subcutaneous xenografts of DU\u2010145, LuCaP\u201035, MDA\u2010PCa\u20102b and intraosseous implants of C4\u20102 human prostate cancers. Intraosseous growth of C4\u20102 tumors was monitored by serum PSA. BN\/GRP receptors were evaluated by <jats:sup>125<\/jats:sup>I\u2010[Tyr<jats:sup>4<\/jats:sup>]BN binding assays and RT\u2010PCR. The effects of AN\u2010215 on apoptosis and cell proliferation were followed by histology, and the expression of Bcl\u20102 and Bax protein was determined by Western blot analysis. Targeted analog AN\u2010215 significantly inhibited growth of subcutaneously implanted DU\u2010145, LuCaP\u201035 and MDA\u2010PCa\u20102b prostate cancers by 81% to 91% compared to controls, while cytotoxic radical AN\u2010201 was less effective and more toxic. Serum PSA levels of mice bearing intraosseous C4\u20102 prostate tumors were significantly reduced. In LuCaP\u201035 tumors administration of BN antagonist RC\u20103095 prior to AN\u2010215 blocked the receptors for BN\/GRP and inhibited the effects of AN\u2010215. High affinity receptors for BN\/GRP and their m\u2010RNA were detected on membranes of all 4 tumor models. Therapy with AN\u2010215, but not with AN\u2010201, decreased the ratio of Bcl\u20102\/Bax in DU\u2010145 and the expression of antiapoptotic Bcl\u20102 in LuCaP\u201035 tumors. The presence of BN\/GRP receptors on primary and metastatic prostate cancers makes possible targeted chemotherapy with AN\u2010215 for the treatment of this malignancy. \u00a9 2005 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.21292","type":"journal-article","created":{"date-parts":[[2005,7,7]],"date-time":"2005-07-07T16:47:15Z","timestamp":1120754835000},"page":"222-229","source":"Crossref","is-referenced-by-count":21,"title":["Targeted chemotherapy with cytotoxic bombesin analogue AN\u2010215 inhibits growth of experimental human prostate cancers"],"prefix":"10.1002","volume":"118","author":[{"given":"Anton","family":"Stangelberger","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew 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