{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T20:05:06Z","timestamp":1787601906058,"version":"build-2736575974"},"reference-count":40,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T00:00:00Z","timestamp":1706745600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009057","name":"Karl-Franzens-Universit\u00e4t Graz","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cancer\u2010associated cachexia (CAC) is a debilitating syndrome associated with poor quality of life and reduced life expectancy of cancer patients. CAC is characterized by unintended body weight reduction due to muscle and adipose tissue loss. A major hallmark of CAC is systemic inflammation. Several non\u2010steroidal anti\u2010inflammatory drugs (NSAIDs) have been suggested for CAC treatment, yet no single medication has proven reliable. R\u2010ketorolac (RK) is the R\u2010enantiomer of a commonly used NSAID. The effect of RK on CAC has not yet been evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Ten\u2010 to 11\u2010week\u2010old mice were inoculated with C26 or CHX207 cancer cells or vehicle control (phosphate\u2010buffered saline [PBS]). After cachexia onset, 2\u00a0mg\/kg RK or PBS was administered daily by oral gavage. Body weight, food intake and tumour size were continuously measured. At study endpoints, blood was drawn, mice were sacrificed and tissues were excised. Immune cell abundance was analysed using a Cytek\u00ae Aurora spectral flow cytometer. Cyclooxygenase (COX) activity was determined in lung homogenates using a fluorometric kit. Muscle tissues were analysed for mRNA and protein expression by quantitative real\u2010time PCR and western blotting analysis, respectively. Muscle fibre size was determined on histological slides after haematoxylin\/eosin staining.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Ten\u2010day survival rate of C26\u2010bearing animals was 10% while RK treatment resulted in a 100% survival rate (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.0009). Chemotherapy resulted in a 10% survival rate 14\u00a0days after treatment initiation, but all mice survived upon co\u2010medication with RK and cyclophosphamide (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.0001). Increased survival was associated with a protection from body weight loss in C26 (\u22120.61\u00a0\u00b1\u00a01.82 vs. \u22124.48\u00a0\u00b1\u00a02.0\u00a0g,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.0004) and CHX207 (\u22120.49\u00a0\u00b1\u00a00.33 vs. \u22122.49\u00a0\u00b1\u00a00.93\u00a0g,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.0003) tumour\u2010bearing mice treated with RK, compared with untreated mice. RK ameliorated musculus quadriceps (\u22121.7\u00a0\u00b1\u00a07.1% vs. \u221227.8\u00a0\u00b1\u00a08.3%,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.0007) and gonadal white adipose tissue (\u221218.8\u00a0\u00b1\u00a049% vs. \u221269\u00a0\u00b1\u00a015.6%,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.094) loss in tumour\u2010bearing mice, compared with untreated mice. Mechanistically, RK reduced circulating interleukin\u20106 (IL\u20106) concentrations from 334\u00a0\u00b1\u00a0151 to 164\u00a0\u00b1\u00a0123\u00a0pg\/mL (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.047) in C26 and from 93\u00a0\u00b1\u00a039 to 35\u00a0\u00b1\u00a06\u00a0pg\/mL (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.0053) in CHX207 tumour\u2010bearing mice. Moreover, RK protected mice from cancer\u2010induced T\u2010lymphopenia (+1.8\u00a0\u00b1\u00a042% vs. \u221249.2\u00a0\u00b1\u00a012.1% in treated vs. untreated mice, respectively). RK was ineffective in ameliorating CAC in thymus\u2010deficient nude mice, indicating that the beneficial effect of RK depends on T\u2010cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>RK improved T\u2010lymphopenia and decreased systemic IL\u20106 concentrations, resulting in alleviation of cachexia and increased survival of cachexigenic tumour\u2010bearing mice, even under chemotherapy and independent of COX inhibition. Considering its potential, we propose that the use of RK should be investigated in patients suffering from CAC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.13422","type":"journal-article","created":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T23:30:40Z","timestamp":1706830240000},"page":"562-574","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["R\u2010ketorolac ameliorates cancer\u2010associated cachexia and prolongs survival of tumour\u2010bearing mice"],"prefix":"10.1002","volume":"15","author":[{"given":"Sophia E.","family":"Chrysostomou","sequence":"first","affiliation":[{"name":"Institute of Molecular Biosciences University of Graz  Graz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Eder","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biosciences University of Graz  Graz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella","family":"Pototschnig","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biosciences University of Graz  Graz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna\u2010Lena","family":"Mayer","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biosciences University of Graz  Graz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Derler","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Sciences University of Graz  Graz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Mussbacher","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Sciences University of Graz  Graz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Schauer","sequence":"additional","affiliation":[{"name":"Diagnostic and Research Institute of Pathology Medical University of Graz  Graz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongxu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Yinuoke Ltd.  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongmei","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Immunology Jilin University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gennie","family":"Liu","sequence":"additional","affiliation":[{"name":"Yinuoke Ltd.  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