{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:23:06Z","timestamp":1788308586833,"version":"build-2803163510"},"reference-count":39,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,11,8]],"date-time":"2022-11-08T00:00:00Z","timestamp":1667865600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Beta\u2010blockers and selected stereoisomers of beta\u2010blockers, like bisoprolol and S\u2010pindolol (ACM\u2010001), have been shown to be effective in preclinical cancer cachexia models. Here, we tested the efficacy of stereoisomers of oxprenolol in two preclinical models of cancer cachexia\u2014the Yoshida AH\u2010130 rat model and the Lewis lung carcinoma (LLC) mouse model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and Results<\/jats:title><jats:p>In the Yoshida AH130 hepatoma rat cancer cachexia model and compared with placebo, 50\u00a0mg\/kg\/d S\u2010oxprenolol (HR: 0.49, 95% CI: 0.28\u20130.85, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.012) was superior to 50\u00a0mg\/kg\/d R\u2010oxprenolol (HR: 0.83, 95% CI 0.38\u20131.45, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.51) in reducing mortality (=\u00a0reaching ethical endpoints). Combination of the three doses (12.5, 25 and 50\u00a0mg\/kg\/d) that had a significant effect on body weight loss in the S\u2010oxprenolol groups vs the same combination of the R\u2010oxprenolol groups lead to a significantly improved survival of S\u2010oxprenolol vs R\u2010oxprenolol (HR: 1.61, 95% CI: 1.08\u20132.39, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.0185). Interestingly, there is a clear dose dependency in S\u2010oxprenolol\u2010treated (5, 12.5, 25 and 50\u00a0mg\/kg\/d) groups, which was not observed in groups treated with R\u2010oxprenolol. A dose\u2010dependent attenuation of weight and lean mass loss by S\u2010oxprenolol was seen in the Yoshida rat model, whereas R\u2010oxprenolol had only had a significant effect on fat mass. S\u2010oxprenolol also non\u2010significantly reduced weight loss in the LLC model and also improved muscle function (grip strength 428\u00a0\u00b1\u00a025 and 539\u00a0\u00b1\u00a037\u00a0g\/100\u00a0g body weight for placebo and S\u2010oxprenolol, respectively). However, there was only a minor effect on quality of life indicators food intake and spontaneous activity in the Yoshida model (25\u00a0mg\/kg\/S\u2010oxprenolol: 11.9\u00a0\u00b1\u00a02.5\u00a0g vs placebo: 4.9\u00a0\u00b1\u00a00.8\u00a0g, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.013 and also vs 25\u00a0mg\/kg\/d R\u2010oxprenolol: 7.5\u00a0\u00b1\u00a02.6\u00a0g, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.025). Both enantiomers had no effects on cardiac dimensions and function at the doses used in this study. Western blotting of proteins involved in the anabolic\/catabolic homoeostasis suggest that anabolic signalling is persevered (IGF\u20101 receptor, Akt) and catabolic signalling is inhibited (FXBO\u201010, TRAF\u20106) by S\u2010pindolol, but not he R\u2010enantiomer. Expression of glucose transporters Glut1 and Glut 4 was similar in all groups, as was AMPK.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>S\u2010oxprenolol is superior to R\u2010oxprenolol in cancer cachexia animal models and shows promise for a human application in cancer cachexia.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.13116","type":"journal-article","created":{"date-parts":[[2022,11,8]],"date-time":"2022-11-08T12:50:49Z","timestamp":1667911849000},"page":"653-660","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["The atypical \u03b2\u2010blocker S\u2010oxprenolol reduces cachexia and improves survival in a rat cancer cachexia model"],"prefix":"10.1002","volume":"14","author":[{"given":"Luping","family":"Yuan","sequence":"first","affiliation":[{"name":"BIH Center for Regenerative Therapies Charit\u00e9\u2010University Medical Center Berlin  Berlin 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de Barcelona (IBUB), Universitat de Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Queralt","family":"Jov\u00e9","sequence":"additional","affiliation":[{"name":"Departament de Bioqu\u00edmica i Biomedicina Molecular, Cancer Research Group, Facultat de Biologia Institut de Biomedicina de la Universitat de Barcelona (IBUB), Universitat de Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edson","family":"Alves de Lima Junior","sequence":"additional","affiliation":[{"name":"Departament de Bioqu\u00edmica i Biomedicina Molecular, Cancer Research Group, Facultat de Biologia Institut de Biomedicina de la Universitat de Barcelona (IBUB), Universitat de Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus S.","family":"Anker","sequence":"additional","affiliation":[{"name":"BIH Center for Regenerative Therapies Charit\u00e9\u2010University Medical Center Berlin  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