{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T03:20:34Z","timestamp":1776223234772,"version":"3.50.1"},"reference-count":30,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"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":["18K15951"],"award-info":[{"award-number":["18K15951"]}],"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":["22K16194"],"award-info":[{"award-number":["22K16194"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Thoracic Cancer"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Drug\u2010induced lung disease (DILD) is a severe adverse event of cancer treatment. Several clinical reports have demonstrated an association between DILD and tumor progression. However, the underlying mechanism remains unclear. This study aimed to elucidate the role of tumor\u2010bearing status in the development of DILD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We prepared a subcutaneous Lewis lung carcinoma (LLC) and KLN205\u2010bearing model. To trigger DILD, bleomycin (BLM) was administered subcutaneously. mRNA expression associated with endothelial activation (PAI\u20101, vWF, and ICAM\u20101), inflammatory cell infiltration, and alveolar wall thickness was assessed by using bronchioalveolar lavage fluid (BALF) and lung tissue. Additionally, the role of high\u2010mobility group box\u00a01 (HMGB1) in tumor\u2010bearing status was examined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compared with control mice, LLC\u2010 and KLN205\u2010bearing mice showed a tendency toward increased expression of at least one of PAI\u20101, vWF, and ICAM\u20101 on endothelium, along with inflammatory cell infiltration in the lungs. BLM\u2010treated mice with LLC showed more inflammatory cell infiltration than BLM\u2010treated mice, accompanied by a significant increase in PAI\u20101, vWF, and ICAM\u20101 expression on endothelium. Moreover, BLM\u2010treated mice with LLC exhibited pronounced alveolar wall thickening. In LLC\u2010bearing mice, serum HMGB1 levels were significantly higher compared with control mice. Additionally, inflammatory cell infiltration in the lungs tended to be increased by the intraperitoneal injection of HMGB1, which was accompanied by increased expression of vWF and ICAM\u20101 on endothelium.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study showed that tumor\u2010bearing status elicits proinflammatory activation in endothelial cells and inflammatory cell infiltration into the lungs that aggravates DILD caused by BLM.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/1759-7714.70272","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T02:05:47Z","timestamp":1774922747000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tumor\u2010Bearing Status Accelerates Bleomycin\u2010Induced Pulmonary Inflammation via Endothelial Activation"],"prefix":"10.1111","volume":"17","author":[{"given":"Shoko","family":"Isoyama","sequence":"first","affiliation":[{"name":"Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Science Hiroshima University  Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9117-1934","authenticated-orcid":false,"given":"Kakuhiro","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Hiroshima University Hospital  Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Iwamoto","sequence":"additional","affiliation":[{"name":"Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Science Hiroshima University  Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasushi","family":"Horimasu","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Hiroshima University Hospital  Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kunihiko","family":"Funaishi","sequence":"additional","affiliation":[{"name":"Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Science Hiroshima University  Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kiyofumi","family":"Shimoji","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Hiroshima University Hospital  Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinjiro","family":"Sakamoto","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Hiroshima University Hospital  Hiroshima 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