{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T19:37:12Z","timestamp":1786390632981,"version":"build-2736575974"},"reference-count":65,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["23K23778"],"award-info":[{"award-number":["23K23778"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["23K05562"],"award-info":[{"award-number":["23K05562"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002241","name":"Japan Science and Technology Agency","doi-asserted-by":"publisher","award":["JPMJSP2108"],"award-info":[{"award-number":["JPMJSP2108"]}],"id":[{"id":"10.13039\/501100002241","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP24ama121053"],"award-info":[{"award-number":["JP24ama121053"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Vet Comparative Oncology"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Effective chemotherapy for canine histiocytic sarcoma (CHS) has yet to be established. In our previous study, CHS cell lines were subclassified into two groups based on their gene expression profiles: Group A and Group B. This study aimed to identify novel therapeutic agents that are effective against each CHS subgroup, and we performed high throughput screening, which examined the effects of 1824 chemical compounds on the 10 CHS cell lines. Among the compounds examined, 73 compounds were identified as candidates to show antiproliferative effects in all CHS cell lines examined, and the median IC\n                    <jats:sub>50<\/jats:sub>\n                    values of 5\u2010fluorouracil and sunitinib were 7.49\u2009\u03bcM and 608\u2009nM, respectively, across all CHS cell lines. While there was no compound that was specifically effective for Group B CHS cell lines, duvelisib was identified as a selective antitumor agent for CHS cell lines in Group A (median IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u2009287\u2009nM), with minimal effects on the other group (median IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009&gt;\u20095\u2009\u03bcM) and normal peripheral blood mononuclear cells (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20097.46\u2009\u03bcM). The amount of phosphorylated Akt protein decreased following duvelisib treatment in all eight CHS cell lines in Group A, but not in cell lines in Group B. Furthermore, duvelisib induced cell cycle arrest and increased cell death in a subset of Group A cell lines. These findings demonstrated that duvelisib exerted antiproliferative effects through inhibition of the Akt pathway in a subset of CHS cell lines while causing minimal cytotoxicity to normal cells.\n                  <\/jats:p>","DOI":"10.1111\/vco.70077","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T04:43:53Z","timestamp":1778733833000},"page":"554-567","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of Novel Therapeutic Agent Candidates Through High Throughput Screening With Chemical Library Based on Molecular Subclassification in Canine Histiocytic Sarcoma Cell Lines"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-4733-3693","authenticated-orcid":false,"given":"Hiroki","family":"Sakuma","sequence":"first","affiliation":[{"name":"Laboratory of Veterinary Internal Medicine, Veterinary Clinical Science Unit, Department of Veterinary Medical Sciences, Graduate School of Agricultural and Life Sciences The University of Tokyo  Bunkyo Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirotaka","family":"Tomiyasu","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Internal Medicine, Veterinary Clinical Science Unit, Department of Veterinary Medical Sciences, Graduate School of Agricultural and Life Sciences The University of Tokyo  Bunkyo Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari","family":"Takamiya","sequence":"additional","affiliation":[{"name":"Drug Discovery Initiative, Graduate School of Pharmaceutical Sciences The University of Tokyo  Bunkyo Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Goto\u2010Koshino","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Internal Medicine, Veterinary Clinical Science Unit, Department of Veterinary Medical Sciences, Graduate School of Agricultural and Life Sciences The University of Tokyo  Bunkyo Tokyo Japan"},{"name":"Veterinary Medical Center, Graduate School of Agricultural and Life Sciences The University of Tokyo  Bunkyo Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2047-4970","authenticated-orcid":false,"given":"Atsushi","family":"Tsukamoto","sequence":"additional","affiliation":[{"name":"Laboratory of Laboratory Animal Science Azabu University  Sagamihara Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Bonkobara","sequence":"additional","affiliation":[{"name":"Department of Veterinary Clinical Pathology Nippon Veterinary and Life Science University  Musashino Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaru","family":"Okuda","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Internal Medicine, Veterinary Clinical Science Unit, Department of Veterinary Medical Sciences, Graduate School of Agricultural and Life Sciences The University of Tokyo  Bunkyo Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/0300985813510413"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cvsm.2019.04.009"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1939-1676.2007.tb02937.x"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/vco.13060"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.5326\/JAAHA-MS-6959"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/vco.12314"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.2460\/javma.21.11.0498"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1939-1676.2010.0588.x"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/vco.12329"},{"issue":"4","key":"e_1_2_9_11_1","first-page":"1137","article-title":"Dabrafenib and Trametinib in Langerhans Cell Histiocytosis and Other Histiocytic Disorders","volume":"109","author":"Cournoyer E.","year":"2024","journal-title":"Haematologica"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-020-00673-x"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.5858\/arpa.2018-0349-RS"},{"key":"e_1_2_9_14_1","first-page":"1","article-title":"Whole Exome and Transcriptome Analysis Revealed the Activation of ERK and Akt Signaling Pathway in Canine Histiocytic Sarcoma","volume":"13","author":"Asada H.","year":"2023","journal-title":"Science Reports"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-17-1273"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/vco.12989"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/jvp.12449"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tvjl.2012.12.016"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tvjl.2024.106264"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/vco.13071"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1517\/17460441.2016.1165203"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1292\/jvms.68.1343"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02623551"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1177\/108705719900400206"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.107.123026"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/vco.12812"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1292\/jvms.14-0415"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.2460\/javma.246.11.1230"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-009-1070-1"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12917-021-02927-5"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-05-786566"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-05-850461"},{"issue":"19","key":"e_1_2_9_33_1","first-page":"5390","article-title":"The Phosphatidylinositol 3\u2010Kinase\/AKT Signal Transduction Pathway Plays a Critical Role in the Expression of p21WAF1\/CIP1\/SDI1 Induced by Cisplatin and Paclitaxel","volume":"60","author":"Mitsuuchi Y.","year":"2000","journal-title":"Cancer Research"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.04.001"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)02554-0"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1011923"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1074"},{"issue":"1","key":"e_1_2_9_38_1","first-page":"327","article-title":"In Vivo Antitumor Activity of SU11248, a Novel Tyrosine Kinase Inhibitor Targeting Vascular Endothelial Growth Factor and Platelet\u2010Derived Growth Factor Receptors: Determination of a Pharmacokinetic\/Pharmacodynamic Relationship","volume":"9","author":"Mendel D. B.","year":"2003","journal-title":"Clinical Cancer Research"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-21-2664"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-024-12584-0"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1753"},{"key":"e_1_2_9_42_1","volume-title":"Role of Nuclear Factor\u2010\u039aB in Melanoma","author":"Amiri K. I.","year":"2005"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1177\/03009858231180484"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj2960297"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20070003"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/35077225"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/366701a0"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90572-X"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2007.10.018"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.15.5.2672"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7809631"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.13.8.773"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2003.12.005"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1136\/jclinpath-2018-205216"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.11.044"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.31087"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1080\/01926230701320337"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.18.00915"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-08-802470"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-023-03689-6"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2020.113355"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.2460\/ajvr.80.7.680"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-11-201"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1111\/vco.12357"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.32991"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes10070505"}],"container-title":["Veterinary and Comparative Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/vco.70077","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/vco.70077","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/vco.70077","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T19:04:22Z","timestamp":1786388662000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/vco.70077"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,13]]},"references-count":65,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1111\/vco.70077"],"URL":"https:\/\/doi.org\/10.1111\/vco.70077","archive":["Portico"],"relation":{},"ISSN":["1476-5810","1476-5829"],"issn-type":[{"value":"1476-5810","type":"print"},{"value":"1476-5829","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,13]]},"assertion":[{"value":"2025-09-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}