{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T11:48:52Z","timestamp":1762084132106,"version":"build-2065373602"},"reference-count":53,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,30]],"date-time":"2022-12-30T00:00:00Z","timestamp":1672358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Eisai (Spain)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Although the overall survival of advanced soft-tissue sarcoma (STS) patients has increased in recent years, the median progression-free survival is lower than 5 months, meaning that there is an unmet need in this population. Among second-line treatments for advanced STS, eribulin is an anti-microtubule agent that has been approved for liposarcoma. Here, we tested the combination of eribulin with gemcitabine in preclinical models of L-sarcoma. The effect in cell viability was measured by MTS and clonogenic assay. Cell cycle profiling was studied by flow cytometry, while apoptosis was measured by flow cytometry and Western blotting. The activity of eribulin plus gemcitabine was evaluated in in vivo patient-derived xenograft (PDX) models. In L-sarcoma cell lines, eribulin plus gemcitabine showed to be synergistic, increasing the number of hypodiploid events (increased subG1 population) and the accumulation of DNA damage. In in vivo PDX models of L-sarcomas, eribulin combined with gemcitabine was a viable scheme, delaying tumour growth after one cycle of treatment, being more effective in leiomyosarcoma. The combination of eribulin and gemcitabine was synergistic in L-sarcoma cultures and it showed to be active in in vivo studies. This combination deserves further exploration in the clinical context.<\/jats:p>","DOI":"10.3390\/ijms24010680","type":"journal-article","created":{"date-parts":[[2023,1,2]],"date-time":"2023-01-02T04:07:09Z","timestamp":1672632429000},"page":"680","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Efficacy of Eribulin Plus Gemcitabine Combination in L-Sarcomas"],"prefix":"10.3390","volume":"24","author":[{"given":"Mar\u00eda","family":"L\u00f3pez-\u00c1lvarez","sequence":"first","affiliation":[{"name":"Institute of Biomedicine of Sevilla, IBIS, Hospital Universitario Virgen del Roc\u00edo-HUVR, Consejo Superior de Investigaciones Cient\u00edficas-CSIC, Universidad de Sevilla, 41013 Sevilla, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Gonz\u00e1lez-Aguilera","sequence":"additional","affiliation":[{"name":"Centro Andaluz de Biolog\u00eda Molecular y Medicina Regenerativa (CABIMER), Universidad de Sevilla-CSIC, Universidad Pablo de Olavide, 41092 Sevilla, Spain"},{"name":"Departamento de Biolog\u00eda Celular, Facultad de Biolog\u00eda, Universidad de Sevilla, 41013 Sevilla, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6514-2419","authenticated-orcid":false,"given":"David S.","family":"Moura","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria Fundaci\u00f3n Jim\u00e9nez Diaz (IIS\/FJD), 28015 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paloma","family":"S\u00e1nchez-Bustos","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine of Sevilla, IBIS, Hospital Universitario Virgen del Roc\u00edo-HUVR, Consejo Superior de Investigaciones Cient\u00edficas-CSIC, Universidad de Sevilla, 41013 Sevilla, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 L.","family":"Mondaza-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria Fundaci\u00f3n Jim\u00e9nez Diaz (IIS\/FJD), 28015 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0711-8979","authenticated-orcid":false,"given":"Marta","family":"Mart\u00edn-Ruiz","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria Fundaci\u00f3n Jim\u00e9nez Diaz (IIS\/FJD), 28015 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Renshaw","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria Fundaci\u00f3n Jim\u00e9nez Diaz (IIS\/FJD), 28015 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafael","family":"Ramos","sequence":"additional","affiliation":[{"name":"Pathology Department, University Hospital Son Espases, 07120 Palma de Mallorca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolina","family":"Castilla","sequence":"additional","affiliation":[{"name":"Nodo Biobanco Hospital Universitario Virgen del Roc\u00edo-Instituto de Biomedicina de Sevilla, Biobanco del SSPA, Unidad de Anatom\u00eda Patol\u00f3gica, Hospital Universitario Virgen del Roc\u00edo, 41013 Sevilla, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8426-3734","authenticated-orcid":false,"given":"Elena","family":"Blanco-Alcaina","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine of Sevilla, IBIS, Hospital Universitario Virgen del Roc\u00edo-HUVR, Consejo Superior de Investigaciones Cient\u00edficas-CSIC, Universidad de Sevilla, 41013 Sevilla, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red C\u00e1ncer (CIBERONC), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5864-762X","authenticated-orcid":false,"given":"Nadia","family":"Hindi","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria Fundaci\u00f3n Jim\u00e9nez Diaz (IIS\/FJD), 28015 Madrid, Spain"},{"name":"Medical Oncology Department, University Hospital Fundaci\u00f3n Jimenez Diaz, 28040 Madrid, Spain"},{"name":"Medical Oncology Department, University Hospital General de Villalba, Collado Villalba, 28400 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7350-6916","authenticated-orcid":false,"given":"Javier","family":"Mart\u00edn-Broto","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria Fundaci\u00f3n Jim\u00e9nez Diaz (IIS\/FJD), 28015 Madrid, Spain"},{"name":"Medical Oncology Department, University Hospital Fundaci\u00f3n Jimenez Diaz, 28040 Madrid, Spain"},{"name":"Medical Oncology Department, University Hospital General de Villalba, Collado Villalba, 28400 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,30]]},"reference":[{"key":"ref_1","unstructured":"WHO Classification of Tumours Editorial Board (2020). 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