Application of LDH assay for therapeutic efficacy evaluation of ex vivo tumor models

Detalhes bibliográficos
Autor(a) principal: Cox, Megan C.
Data de Publicação: 2021
Outros Autores: Mendes, Rita, Silva, Fernanda, Mendes, Teresa F., Zelaya-Lazo, Adelyn, Halwachs, Kathleen, Purkal, Julie J., Isidro, Inês A., Félix, Ana, Boghaert, Erwin R., Brito, Catarina
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/126482
Resumo: Funding Information: This work was supported by AbbVie and by iNOVA4Health – UIDB/04462/2020, a program financially supported by Fundação para a Ciência e Tecnologia (FCT) / Ministério da Educação e Ciência, through national funds. RM and TFM were recipients of PhD fellowships funded by FCT (SFRH/BD/132163/2017 and PD/BD/128377/2017, respectively) and CB was funded by “The Discoveries Centre for Regenerative and Precision Medicine” (European Commission Horizon 2020 Research and Innovation programme, under the Grant Agreement 739572). Publisher Copyright: © 2021, The Author(s).
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spelling Application of LDH assay for therapeutic efficacy evaluation of ex vivo tumor modelsGeneralFunding Information: This work was supported by AbbVie and by iNOVA4Health – UIDB/04462/2020, a program financially supported by Fundação para a Ciência e Tecnologia (FCT) / Ministério da Educação e Ciência, through national funds. RM and TFM were recipients of PhD fellowships funded by FCT (SFRH/BD/132163/2017 and PD/BD/128377/2017, respectively) and CB was funded by “The Discoveries Centre for Regenerative and Precision Medicine” (European Commission Horizon 2020 Research and Innovation programme, under the Grant Agreement 739572). Publisher Copyright: © 2021, The Author(s).The current standard preclinical oncology models are not able to fully recapitulate therapeutic targets and clinically relevant disease biology, evidenced by the 90% attrition rate of new therapies in clinical trials. Three-dimensional (3D) culture systems have the potential to enhance the relevance of preclinical models. However, the limitations of currently available cellular assays to accurately evaluate therapeutic efficacy in these models are hindering their widespread adoption. We assessed the compatibility of the lactate dehydrogenase (LDH) assay in 3D spheroid cultures against other commercially available readout methods. We developed a standardized protocol to apply the LDH assay to ex vivo cultures, considering the impact of culture growth dynamics. We show that accounting for growth rates and background release levels of LDH are sufficient to make the LDH assay a suitable methodology for longitudinal monitoring and endpoint assessment of therapeutic efficacy in both cell line-derived xenografts (xenospheres) and patient-derived explant cultures. This method has the added value of being non-destructive and not dependent on reagent penetration or manipulation of the parent material. The establishment of reliable readout methods for complex 3D culture systems will further the utility of these tumor models in preclinical and co-clinical drug development studies.Instituto de Tecnologia Química e Biológica António Xavier (ITQB)Centro de Estudos de Doenças Crónicas (CEDOC)NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)RUNCox, Megan C.Mendes, RitaSilva, FernandaMendes, Teresa F.Zelaya-Lazo, AdelynHalwachs, KathleenPurkal, Julie J.Isidro, Inês A.Félix, AnaBoghaert, Erwin R.Brito, Catarina2021-10-22T03:43:07Z2021-122021-12-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/126482eng2045-2322PURE: 34091209https://doi.org/10.1038/s41598-021-97894-0info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T05:06:54Zoai:run.unl.pt:10362/126482Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:45:53.829806Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Application of LDH assay for therapeutic efficacy evaluation of ex vivo tumor models
title Application of LDH assay for therapeutic efficacy evaluation of ex vivo tumor models
spellingShingle Application of LDH assay for therapeutic efficacy evaluation of ex vivo tumor models
Cox, Megan C.
General
title_short Application of LDH assay for therapeutic efficacy evaluation of ex vivo tumor models
title_full Application of LDH assay for therapeutic efficacy evaluation of ex vivo tumor models
title_fullStr Application of LDH assay for therapeutic efficacy evaluation of ex vivo tumor models
title_full_unstemmed Application of LDH assay for therapeutic efficacy evaluation of ex vivo tumor models
title_sort Application of LDH assay for therapeutic efficacy evaluation of ex vivo tumor models
author Cox, Megan C.
author_facet Cox, Megan C.
Mendes, Rita
Silva, Fernanda
Mendes, Teresa F.
Zelaya-Lazo, Adelyn
Halwachs, Kathleen
Purkal, Julie J.
Isidro, Inês A.
Félix, Ana
Boghaert, Erwin R.
Brito, Catarina
author_role author
author2 Mendes, Rita
Silva, Fernanda
Mendes, Teresa F.
Zelaya-Lazo, Adelyn
Halwachs, Kathleen
Purkal, Julie J.
Isidro, Inês A.
Félix, Ana
Boghaert, Erwin R.
Brito, Catarina
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Instituto de Tecnologia Química e Biológica António Xavier (ITQB)
Centro de Estudos de Doenças Crónicas (CEDOC)
NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
RUN
dc.contributor.author.fl_str_mv Cox, Megan C.
Mendes, Rita
Silva, Fernanda
Mendes, Teresa F.
Zelaya-Lazo, Adelyn
Halwachs, Kathleen
Purkal, Julie J.
Isidro, Inês A.
Félix, Ana
Boghaert, Erwin R.
Brito, Catarina
dc.subject.por.fl_str_mv General
topic General
description Funding Information: This work was supported by AbbVie and by iNOVA4Health – UIDB/04462/2020, a program financially supported by Fundação para a Ciência e Tecnologia (FCT) / Ministério da Educação e Ciência, through national funds. RM and TFM were recipients of PhD fellowships funded by FCT (SFRH/BD/132163/2017 and PD/BD/128377/2017, respectively) and CB was funded by “The Discoveries Centre for Regenerative and Precision Medicine” (European Commission Horizon 2020 Research and Innovation programme, under the Grant Agreement 739572). Publisher Copyright: © 2021, The Author(s).
publishDate 2021
dc.date.none.fl_str_mv 2021-10-22T03:43:07Z
2021-12
2021-12-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10362/126482
url http://hdl.handle.net/10362/126482
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 2045-2322
PURE: 34091209
https://doi.org/10.1038/s41598-021-97894-0
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
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