{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T05:13:14Z","timestamp":1791263594885,"version":"4.1.0"},"reference-count":21,"publisher":"Wiley","license":[{"start":{"date-parts":[[2012,1,1]],"date-time":"2012-01-01T00:00:00Z","timestamp":1325376000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["CA 112270"],"award-info":[{"award-number":["CA 112270"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Leiomyosarcoma Foundation","award":["CA 112270"],"award-info":[{"award-number":["CA 112270"]}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["CA 112270"],"award-info":[{"award-number":["CA 112270"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sarcoma"],"published-print":{"date-parts":[[2012]]},"abstract":"<jats:p>Leiomyosarcoma (LMS) is a malignant, soft-tissue tumor for which few effective therapies exist. Previously, we showed that there are three molecular subtypes of LMS. Here, we analyzed genes differentially expressed in each of the three LMS subtypes as compared to benign leiomyomas and then used the Connectivity Map (cmap) to calculate enrichment scores for the 1309 cmap drugs in order to identify candidate molecules with the potential to induce a benign, leiomyoma-like phenotype in LMS cells. 11 drugs were selected and tested for their ability to inhibit the growth of three human LMS cell lines. We identified two drugs with<jats:italic>in vitro<\/jats:italic>efficacy against LMS, one of which had a strongly negative enrichment score (Cantharidin) and the other of which had a strongly positive enrichment score (MG-132). Given MG-132\u2019s strong inhibitory effect on LMS cell viability, we hypothesized that LMS cells may be sensitive to treatment with other proteasome inhibitors and demonstrated that bortezomib, a clinically-approved proteasome inhibitor not included in the original cmap screen, potently inhibited the viability of the LMS cell lines. These findings suggest that systematically linking LMS subtype-specific expression signatures with drug-associated expression profiles represents a promising approach for the identification of new drugs for LMS.<\/jats:p>","DOI":"10.1155\/2012\/805614","type":"journal-article","created":{"date-parts":[[2012,8,5]],"date-time":"2012-08-05T17:01:17Z","timestamp":1344186077000},"page":"1-9","source":"Crossref","is-referenced-by-count":12,"title":["Comparative Gene Expression Profiling of Benign and Malignant Lesions Reveals Candidate Therapeutic Compounds for Leiomyosarcoma"],"prefix":"10.1155","volume":"2012","author":[{"given":"Badreddin","family":"Edris","sequence":"first","affiliation":[{"name":"Department of Pathology, Stanford University Medical Center, Stanford, CA 93205, USA"},{"name":"Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan A.","family":"Fletcher","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert B.","family":"West","sequence":"additional","affiliation":[{"name":"Department of Pathology, Stanford University Medical Center, Stanford, CA 93205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matt","family":"van de Rijn","sequence":"additional","affiliation":[{"name":"Department of Pathology, Stanford University Medical Center, Stanford, CA 93205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew H.","family":"Beck","sequence":"additional","affiliation":[{"name":"Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","reference":[{"key":"1","first-page":"131","volume-title":"Pathology and genetics of tumours of soft tissue and bone","year":"2002"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2009.381"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2009.09.023"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.1126\/science.1132939"},{"key":"5","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2044"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-08-2699"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-08-2432"},{"key":"8","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3001318"},{"key":"9","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.091062498"},{"key":"10","doi-asserted-by":"publisher","DOI":"10.1186\/1749-8546-2-8"},{"key":"11","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2004.12.003"},{"key":"12","doi-asserted-by":"publisher","DOI":"10.1097\/01.cad.0000217428.90325.35"},{"key":"13","doi-asserted-by":"publisher","DOI":"10.1016\/S0962-8924(98)01346-4"},{"key":"14","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-1673"},{"key":"15","doi-asserted-by":"publisher","DOI":"10.1007\/s12079-011-0121-7"},{"key":"16","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.20968"},{"key":"18","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-006-0216-7"},{"key":"19","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-2671"},{"key":"20","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/29.1.152"},{"key":"21","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-4004"},{"key":"22","doi-asserted-by":"publisher","DOI":"10.1002\/path.3986"}],"container-title":["Sarcoma"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/sarcoma\/2012\/805614.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/sarcoma\/2012\/805614.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/sarcoma\/2012\/805614.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2016,8,2]],"date-time":"2016-08-02T16:57:18Z","timestamp":1470157038000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.hindawi.com\/journals\/sarcoma\/2012\/805614\/"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012]]},"references-count":21,"alternative-id":["805614","805614"],"URL":"https:\/\/doi.org\/10.1155\/2012\/805614","relation":{},"ISSN":["1357-714X","1369-1643"],"issn-type":[{"value":"1357-714X","type":"print"},{"value":"1369-1643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012]]}}}