Efficacy of Eribulin Plus Gemcitabine Combination in L-Sarcomas

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-microtub...

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Autores: López-Álvarez, María, González-Aguilera, Cristina, Moura, David S, Sanchez-Bustos, Paloma, Mondaza-Hernández, José L, Martín-Ruiz, Marta, Renshaw, Marta, Ramos-Asensio, Rafael, Castilla, Carolina, Blanco-Alcaina, Elena, Hindi, Nadia, Martín-Broto, Javier
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Conselleria de Salut i Consum del Govern de les Illes Balears
Repositorio:Docusalut
Idioma:inglés
OAI Identifier:oai:docusalut.com:20.500.13003/19018
Acceso en línea:https://hdl.handle.net/20.500.13003/19018
Access Level:acceso abierto
Palabra clave:Leiomyosarcoma
Humans
Ketones
Sarcoma
Soft Tissue Neoplasms
Furans
Furanos
Cetonas
Humanos
Neoplasias de los Tejidos Blandos
Leiomiosarcoma
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spelling Efficacy of Eribulin Plus Gemcitabine Combination in L-SarcomasLópez-Álvarez, MaríaGonzález-Aguilera, CristinaMoura, David SSanchez-Bustos, PalomaMondaza-Hernández, José LMartín-Ruiz, MartaRenshaw, MartaRamos-Asensio, RafaelCastilla, CarolinaBlanco-Alcaina, ElenaHindi, NadiaMartín-Broto, JavierLeiomyosarcomaHumansKetonesSarcomaSoft Tissue NeoplasmsFuransSarcomaFuranosCetonasHumanosNeoplasias de los Tejidos BlandosSarcomaLeiomiosarcomaAlthough 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.MDPI20222022-12-3020222022-12-30research articlehttp://purl.org/coar/resource_type/c_2df8fbb1info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.13003/19018reponame:Docusalutinstname:Conselleria de Salut i Consum del Govern de les Illes BalearsInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Atribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:docusalut.com:20.500.13003/190182026-06-22T12:44:07Z
dc.title.none.fl_str_mv Efficacy of Eribulin Plus Gemcitabine Combination in L-Sarcomas
title Efficacy of Eribulin Plus Gemcitabine Combination in L-Sarcomas
spellingShingle Efficacy of Eribulin Plus Gemcitabine Combination in L-Sarcomas
López-Álvarez, María
Leiomyosarcoma
Humans
Ketones
Sarcoma
Soft Tissue Neoplasms
Furans
Sarcoma
Furanos
Cetonas
Humanos
Neoplasias de los Tejidos Blandos
Sarcoma
Leiomiosarcoma
title_short Efficacy of Eribulin Plus Gemcitabine Combination in L-Sarcomas
title_full Efficacy of Eribulin Plus Gemcitabine Combination in L-Sarcomas
title_fullStr Efficacy of Eribulin Plus Gemcitabine Combination in L-Sarcomas
title_full_unstemmed Efficacy of Eribulin Plus Gemcitabine Combination in L-Sarcomas
title_sort Efficacy of Eribulin Plus Gemcitabine Combination in L-Sarcomas
dc.creator.none.fl_str_mv López-Álvarez, María
González-Aguilera, Cristina
Moura, David S
Sanchez-Bustos, Paloma
Mondaza-Hernández, José L
Martín-Ruiz, Marta
Renshaw, Marta
Ramos-Asensio, Rafael
Castilla, Carolina
Blanco-Alcaina, Elena
Hindi, Nadia
Martín-Broto, Javier
author López-Álvarez, María
author_facet López-Álvarez, María
González-Aguilera, Cristina
Moura, David S
Sanchez-Bustos, Paloma
Mondaza-Hernández, José L
Martín-Ruiz, Marta
Renshaw, Marta
Ramos-Asensio, Rafael
Castilla, Carolina
Blanco-Alcaina, Elena
Hindi, Nadia
Martín-Broto, Javier
author_role author
author2 González-Aguilera, Cristina
Moura, David S
Sanchez-Bustos, Paloma
Mondaza-Hernández, José L
Martín-Ruiz, Marta
Renshaw, Marta
Ramos-Asensio, Rafael
Castilla, Carolina
Blanco-Alcaina, Elena
Hindi, Nadia
Martín-Broto, Javier
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv
dc.subject.none.fl_str_mv Leiomyosarcoma
Humans
Ketones
Sarcoma
Soft Tissue Neoplasms
Furans
Sarcoma
Furanos
Cetonas
Humanos
Neoplasias de los Tejidos Blandos
Sarcoma
Leiomiosarcoma
topic Leiomyosarcoma
Humans
Ketones
Sarcoma
Soft Tissue Neoplasms
Furans
Sarcoma
Furanos
Cetonas
Humanos
Neoplasias de los Tejidos Blandos
Sarcoma
Leiomiosarcoma
description 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.
publishDate 2022
dc.date.none.fl_str_mv 2022
2022-12-30
2022
2022-12-30
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.13003/19018
url https://hdl.handle.net/20.500.13003/19018
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Docusalut
instname:Conselleria de Salut i Consum del Govern de les Illes Balears
instname_str Conselleria de Salut i Consum del Govern de les Illes Balears
reponame_str Docusalut
collection Docusalut
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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