{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T15:42:43Z","timestamp":1772811763388,"version":"3.50.1"},"reference-count":50,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2009,6,19]],"date-time":"2009-06-19T00:00:00Z","timestamp":1245369600000},"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":[[2009,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Osteosarcoma (OSA), the most common malignant bone tumor in dogs and children, exhibits a similar clinical presentation and molecular biology in both species. Unfortunately, 30\u201340% of children and 90% of dogs still die of disease despite aggressive therapy. The purpose of this study was to test the biologic activity of a novel heat shock protein 90 (HSP90) inhibitor, STA\u20101474, against OSA. Canine and human OSA cell lines and normal canine osteoblasts were treated with STA\u20101474 and evaluated for effects on proliferation (CyQuant), apoptosis (Annexin V, PARP cleavage, caspase 3\/7 activation) and known HSP90 client proteins. HSP90 was immunoprecipitated from normal and malignant osteoblasts and Western blotting for co\u2010chaperones was performed. Mice bearing canine OSA xenografts were treated with STA\u20101474, and tumors samples were evaluated for caspase\u20103 activation and loss of p\u2010Akt\/Akt. Treatment with STA\u20101474 promoted loss of cell viability, inhibition of cell proliferation and induction of apoptosis in OSA cell lines. STA\u20101474 and its active metabolite STA\u20109090 also demonstrated increased potency compared to 17\u2010AAG. STA\u20101474 exhibited selectivity for OSA cells <jats:italic>versus<\/jats:italic> normal canine osteoblasts, and HSP90 co\u2010precipitated with co\u2010chaperones p23 and Hop in canine OSA cells but not in normal canine osteoblasts. Furthermore, STA\u20101474 downregulated the expression of p\u2010Met\/Met, p\u2010Akt\/Akt and p\u2010STAT3. Finally, STA\u20101474 induced tumor regression, caspase\u20103 activation and downregulation of p\u2010Met\/Met and p\u2010Akt\/Akt in OSA xenografts. Together, these data suggest that HSP90 represents a relevant target for therapeutic intervention in OSA. \u00a9 2009 UICC<\/jats:p>","DOI":"10.1002\/ijc.24660","type":"journal-article","created":{"date-parts":[[2009,6,19]],"date-time":"2009-06-19T18:05:39Z","timestamp":1245434739000},"page":"2792-2801","source":"Crossref","is-referenced-by-count":71,"title":["The novel HSP90 inhibitor STA\u20101474 exhibits biologic activity against osteosarcoma cell lines"],"prefix":"10.1002","volume":"125","author":[{"given":"Jennifer K.","family":"McCleese","sequence":"first","affiliation":[]},{"given":"Misty D.","family":"Bear","sequence":"additional","affiliation":[]},{"given":"Stacey L.","family":"Fossey","sequence":"additional","affiliation":[]},{"given":"Robert M.","family":"Mihalek","sequence":"additional","affiliation":[]},{"given":"Kevin P.","family":"Foley","sequence":"additional","affiliation":[]},{"given":"Weiwen","family":"Ying","sequence":"additional","affiliation":[]},{"given":"James","family":"Barsoum","sequence":"additional","affiliation":[]},{"given":"Cheryl A.","family":"London","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2009,8,24]]},"reference":[{"key":"e_1_2_6_2_2","first-page":"155","article-title":"Comparative biology of human and canine osteosarcoma","volume":"27","author":"Mueller F","year":"2007","journal-title":"Anticancer Res"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2003.08.006"},{"key":"e_1_2_6_4_2","volume-title":"Small animal clinical oncology","author":"Withrow SJ","year":"2001"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1354\/vp.41-3-291"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm982"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5829.2007.00137.x"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1025404603315"},{"key":"e_1_2_6_9_2","first-page":"19","article-title":"Comparative gene expression profiling of canine and human osteosarcoma","volume":"4","author":"Paoloni M","year":"2006","journal-title":"Proceedings of the Genes Dogs and Cancer: Fourth International Canine Cancer Conference"},{"key":"e_1_2_6_10_2","first-page":"2406","article-title":"A randomized controlled trial of octreotide pamoate long\u2010acting release and carboplatin versus carboplatin alone in dogs with naturally occurring osteosarcoma: evaluation of insulin\u2010like growth factor suppression and chemotherapy","volume":"8","author":"Khanna C","year":"2002","journal-title":"Clin Cancer Res"},{"key":"e_1_2_6_11_2","first-page":"1595","article-title":"Adjuvant therapy for osteosarcoma in dogs: results of randomized clinical trials using combined liposome\u2010encapsulated muramyl tripeptide and cisplatin","volume":"1","author":"Kurzman ID","year":"1995","journal-title":"Clin Cancer Res"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.3109\/10611869408996814"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1939-1676.2007.tb03022.x"},{"key":"e_1_2_6_14_2","first-page":"159","article-title":"Comparative aspects of osteosarcoma. 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