{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T15:15:14Z","timestamp":1778771714146,"version":"3.51.4"},"reference-count":14,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,8,17]],"date-time":"2017-08-17T00:00:00Z","timestamp":1502928000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Grant-in-Aid for Scientific Research","award":["15H04601"],"award-info":[{"award-number":["15H04601"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vet Pharm &amp; Therapeutics"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:p>Canine histiocytic sarcoma (<jats:styled-content style=\"fixed-case\">HS<\/jats:styled-content>) is an aggressive and highly metastatic tumor. Previously, the kinase inhibitor dasatinib was shown to have potent growth inhibitory activity against <jats:styled-content style=\"fixed-case\">HS<\/jats:styled-content> cells in vitro, possibly via targeting the <jats:styled-content style=\"fixed-case\">EPHA<\/jats:styled-content>2 receptor. Here, the in vivo effect of dasatinib in <jats:styled-content style=\"fixed-case\">HS<\/jats:styled-content> cells was investigated using a xenograft mouse model. Moreover, the expression status of <jats:styled-content style=\"fixed-case\">EPHA<\/jats:styled-content>2 was examined in six <jats:styled-content style=\"fixed-case\">HS<\/jats:styled-content> cell lines, ranging from insensitive to highly sensitive to dasatinib. In the <jats:styled-content style=\"fixed-case\">HS<\/jats:styled-content> xenograft mouse model, dasatinib significantly suppressed tumor growth, as illustrated by a decrease in mitotic and Ki67 indices and an increase in apoptotic index in tumor tissues. On Western blot analysis, <jats:styled-content style=\"fixed-case\">EPHA<\/jats:styled-content>2 was only weakly detected in all <jats:styled-content style=\"fixed-case\">HS<\/jats:styled-content> cell lines, regardless of sensitivity to dasatinib. Dasatinib likely results in the inhibition of xenograft tumor growth via a mechanism other than targeting <jats:styled-content style=\"fixed-case\">EPHA<\/jats:styled-content>2. The findings of this study suggest that dasatinib is a targeted therapy drug worthy of further exploration for the treatment of canine <jats:styled-content style=\"fixed-case\">HS<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/jvp.12449","type":"journal-article","created":{"date-parts":[[2017,8,18]],"date-time":"2017-08-18T04:16:38Z","timestamp":1503029798000},"source":"Crossref","is-referenced-by-count":7,"title":["Effect of dasatinib in a xenograft mouse model of canine histiocytic sarcoma and in vitro expression status of its potential target <scp>EPHA<\/scp>2"],"prefix":"10.1111","volume":"41","author":[{"given":"K.","family":"Ito","sequence":"first","affiliation":[{"name":"Department of Veterinary Clinical Pathology Nippon Veterinary and Life Science University  Musashino\u2010shi Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Miyamoto","sequence":"additional","affiliation":[{"name":"Department of Veterinary Clinical Pathology Nippon Veterinary and Life Science University  Musashino\u2010shi Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.","family":"Tani","sequence":"additional","affiliation":[{"name":"Department of Veterinary Clinical Pathology Nippon Veterinary and Life Science University  Musashino\u2010shi Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Kurita","sequence":"additional","affiliation":[{"name":"Department of Veterinary Clinical Pathology Nippon Veterinary and Life Science University  Musashino\u2010shi Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Veterinary Clinical Pathology Nippon Veterinary and Life Science University  Musashino\u2010shi Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.","family":"Tamura","sequence":"additional","affiliation":[{"name":"Department of Veterinary Clinical Pathology Nippon Veterinary and Life Science University  Musashino\u2010shi Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0054-7730","authenticated-orcid":false,"given":"M.","family":"Bonkobara","sequence":"additional","affiliation":[{"name":"Department of Veterinary Clinical Pathology Nippon Veterinary and Life Science University  Musashino\u2010shi Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,8,17]]},"reference":[{"key":"e_1_2_4_2_1","doi-asserted-by":"publisher","DOI":"10.1292\/jvms.68.1343"},{"key":"e_1_2_4_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1207247"},{"key":"e_1_2_4_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.075085"},{"key":"e_1_2_4_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5810.2006.00090.x"},{"key":"e_1_2_4_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tvjl.2013.08.003"},{"key":"e_1_2_4_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tvjl.2012.12.016"},{"key":"e_1_2_4_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-007-0478-8"},{"key":"e_1_2_4_9_1","doi-asserted-by":"publisher","DOI":"10.2460\/javma.239.1.90"},{"key":"e_1_2_4_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm049486a"},{"key":"e_1_2_4_11_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-06-1112"},{"key":"e_1_2_4_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tranon.2015.03.006"},{"key":"e_1_2_4_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2007.11.005"},{"key":"e_1_2_4_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa055229"},{"key":"e_1_2_4_15_1","doi-asserted-by":"publisher","DOI":"10.1517\/14728222.2011.538682"}],"container-title":["Journal of Veterinary Pharmacology and Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjvp.12449","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jvp.12449","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T21:54:11Z","timestamp":1695938051000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jvp.12449"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,8,17]]},"references-count":14,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2018,2]]}},"alternative-id":["10.1111\/jvp.12449"],"URL":"https:\/\/doi.org\/10.1111\/jvp.12449","archive":["Portico"],"relation":{},"ISSN":["0140-7783","1365-2885"],"issn-type":[{"value":"0140-7783","type":"print"},{"value":"1365-2885","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,8,17]]}}}