{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T14:26:44Z","timestamp":1793111204503,"version":"4.5.0"},"reference-count":48,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,6,2]],"date-time":"2022-06-02T00:00:00Z","timestamp":1654128000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["MOST 107-2320-B-016-011-MY3"],"award-info":[{"award-number":["MOST 107-2320-B-016-011-MY3"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["TSGH-E-111232"],"award-info":[{"award-number":["TSGH-E-111232"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["MND-MAB-D-111136"],"award-info":[{"award-number":["MND-MAB-D-111136"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010425","name":"Tri-Service General Hospital","doi-asserted-by":"publisher","award":["MOST 107-2320-B-016-011-MY3"],"award-info":[{"award-number":["MOST 107-2320-B-016-011-MY3"]}],"id":[{"id":"10.13039\/501100010425","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010425","name":"Tri-Service General Hospital","doi-asserted-by":"publisher","award":["TSGH-E-111232"],"award-info":[{"award-number":["TSGH-E-111232"]}],"id":[{"id":"10.13039\/501100010425","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010425","name":"Tri-Service General Hospital","doi-asserted-by":"publisher","award":["MND-MAB-D-111136"],"award-info":[{"award-number":["MND-MAB-D-111136"]}],"id":[{"id":"10.13039\/501100010425","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of National Defense-Medical Affairs Bureau","award":["MOST 107-2320-B-016-011-MY3"],"award-info":[{"award-number":["MOST 107-2320-B-016-011-MY3"]}]},{"name":"Ministry of National Defense-Medical Affairs Bureau","award":["TSGH-E-111232"],"award-info":[{"award-number":["TSGH-E-111232"]}]},{"name":"Ministry of National Defense-Medical Affairs Bureau","award":["MND-MAB-D-111136"],"award-info":[{"award-number":["MND-MAB-D-111136"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Lung cancer-related pleural fluid (LCPF) presents as a common complication with limited treatment. Beyond its function in lipid digestion, bile acid was identified as a potent carcinogen to stimulate tumor proliferation. Previous research indicated a correlation between serum bile acid levels and the risk of developing several gastrointestinal cancers. Our study identified elevated bile acid levels in LCPF and increased farnesoid X receptor (FXR) expression as bile acid nuclear receptors in pleural microvessels of lung adenocarcinoma. Additionally, LCPF stimulated the expression of proteins involved in bile acid synthesis and cholesterol metabolism in HUVECs including CYP7A1, StAR, HMGCR, and SREBP2. LCPF-induced endothelial motility and angiogenesis were counteracted by using \u03b2-muricholic acid as an FXR antagonist. Moreover, we investigated the efficacy of cholesterol-lowering medications, such as cholestyramine, fenofibrate, and atorvastatin, in regulating LCPF-regulated angiogenesis. Along with suppressing endothelial proliferation and angiogenesis, atorvastatin treatment reversed cholesterol accumulation and endothelial junction disruption caused by LCPF. Statin treatment inhibited LCPF-induced endothelial FXR expression as well as the downstream proteins RXR and SHP. Based on the positive findings of suppressing endothelial angiogenesis, our group further incorporated the effect of statin on clinical patients complicated with LCPF. A Kaplan\u2013Meier analysis revealed the clinical benefit of statin exposure in patients with lung adenocarcinoma with LCPF. Conclusively, our study demonstrated the ability of statin to alleviate LCPF-induced angiogenesis in patients with LCPF via FXR modulation.<\/jats:p>","DOI":"10.3390\/cancers14112765","type":"journal-article","created":{"date-parts":[[2022,6,2]],"date-time":"2022-06-02T11:05:02Z","timestamp":1654167902000},"page":"2765","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Survival Benefit of Statin with Anti-Angiogenesis Efficacy in Lung Cancer-Associated Pleural Fluid through FXR Modulation"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9783-5423","authenticated-orcid":false,"given":"Chen-Liang","family":"Tsai","sequence":"first","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Ying","family":"Changchien","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan"},{"name":"Department of Biology and Anatomy, National Defense Medical Center, Taipei 114, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6303-5858","authenticated-orcid":false,"given":"Ying","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biology and Anatomy, National Defense Medical Center, Taipei 114, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chine-Rui","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Biology and Anatomy, National Defense Medical Center, Taipei 114, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tzu-Min","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biology and Anatomy, National Defense Medical Center, Taipei 114, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5824-7079","authenticated-orcid":false,"given":"Hsin-Han","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Biology and Anatomy, National Defense Medical Center, Taipei 114, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1085-9014","authenticated-orcid":false,"given":"Wen-Chiuan","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6229-8189","authenticated-orcid":false,"given":"Yu-Ling","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao-Chung","family":"Tsai","sequence":"additional","affiliation":[{"name":"Division of Chest Medicine, Department of Internal Medicine, Tri-Service General Hospital Songshan Branch, Taipei 105, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hung-Yi","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chieh-Yung","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Sheng","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Taichung Armed Force General Hospital, Taichung 411, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8382-9820","authenticated-orcid":false,"given":"Yu-Huei","family":"Lin","sequence":"additional","affiliation":[{"name":"Post-Baccalaureate Program in Nursing, College of Nursing, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1194\/jlr.M033423","article-title":"Differential regulation of bile acid and cholesterol metabolism by the farnesoid X receptor in Ldlr\u2212\/\u2212 mice versus hamsters","volume":"54","author":"Chaput","year":"2013","journal-title":"J. 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