{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:04:29Z","timestamp":1792785869189,"version":"4.5.0"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2023,10,9]],"date-time":"2023-10-09T00:00:00Z","timestamp":1696809600000},"content-version":"vor","delay-in-days":38,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"JSPS KAKENHI","award":["21H02915"],"award-info":[{"award-number":["21H02915"]}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["21bm0804008h0005"],"award-info":[{"award-number":["21bm0804008h0005"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,9,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Doxorubicin is used in classical chemotherapy for several cancer types. Doxorubicin-induced cardiomyopathy (DOX-CM) is a critical issue among cancer patients. However, differentiating the diagnosis of DOX-CM from that of other cardiomyopathies is difficult. Therefore, in this study, we aimed to determine novel histopathological characteristics to diagnose DOX-CM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Twelve consecutive patients with DOX-CM who underwent cardiac histopathological examination in two medical centres were included. Twelve patients with dilated cardiomyopathy, who were matched with DOX-CM patients in terms of age, sex, and left ventricular ejection fraction, formed the control group. Another control group comprised five consecutive patients with cancer therapy-related cardiac dysfunction induced by tyrosine kinase inhibitors or vascular endothelial growth factor inhibitors were the controls. The positive area of tenascin-C, number of infiltrating macrophages, and presence of p62- and ubiquitin-positive cardiomyocytes were evaluated. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were used for in vitro investigation. The myocardium exhibited significantly greater tenascin-C-positive area and macrophage number in the DOX-CM group than in the control groups (P &amp;lt; 0.01). The tenascin-C-positive area correlated with the number of both CD68- and CD163-positive cells (r = 0.748 and r = 0.656, respectively). Immunostaining for p62 was positive in 10 (83%) patients with DOX-CM. Furthermore, western blotting analysis revealed significant increase in tenascin-C levels in hiPSC-CMs upon doxorubicin treatment (P &amp;lt; 0.05).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The combined histopathological assessment for tenascin-C, macrophages, and p62\/ubiquitin may serve as a novel tool for the diagnosis of DOX-CM. Doxorubicin may directly affect the expression of tenascin-C in the myocardium.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ehjopen\/oead104","type":"journal-article","created":{"date-parts":[[2023,10,9]],"date-time":"2023-10-09T09:33:12Z","timestamp":1696843992000},"source":"Crossref","is-referenced-by-count":4,"title":["Tenascin-C as a potential marker for immunohistopathology of doxorubicin-induced cardiomyopathy"],"prefix":"10.1093","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3754-8593","authenticated-orcid":false,"given":"Tatsuya","family":"Nishikawa","sequence":"first","affiliation":[{"name":"Department of Onco-Cardiology, Osaka International Cancer Institute , 3-1-69, Otemae, Chuo-ku, Osaka City, Osaka 541-8567 , Japan"},{"name":"Department of Cardiovascular Medicine, Akashi Medical Center , Hyogo , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4418-7834","authenticated-orcid":false,"given":"Mikio","family":"Shiba","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine , Suita, Osaka , Japan"},{"name":"Cardiovascular Division, Osaka Police Hospital , Osaka , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiko","family":"Ikeda","sequence":"additional","affiliation":[{"name":"Department of Pathology, National Cerebral and Cardiovascular Center , 6-1, Kishibeshinmachi , Suita, Osaka 564-8565, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9822-3461","authenticated-orcid":false,"given":"Keiko","family":"Ohta-Ogo","sequence":"additional","affiliation":[{"name":"Department of Pathology, National Cerebral and Cardiovascular Center , 6-1, Kishibeshinmachi , Suita, Osaka 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Osaka , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hatsue","family":"Ishibashi-Ueda","sequence":"additional","affiliation":[{"name":"Department of Pathology, National Cerebral and Cardiovascular Center , 6-1, Kishibeshinmachi , Suita, Osaka 564-8565, Japan"},{"name":"Department of Pathology, Hokusetsu General Hospital , Takatsuki, Osaka , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiichiro","family":"Honma","sequence":"additional","affiliation":[{"name":"Department of Pathology, Osaka International Cancer Institute , Osaka , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chisato","family":"Izumi","sequence":"additional","affiliation":[{"name":"Department of Heart Failure and Transplantation, National Cerebral and Cardiovascular Center , Suita, Osaka , 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