Application of LDH assay for therapeutic efficacy evaluation of ex vivo tumor models
| العنوان: | Application of LDH assay for therapeutic efficacy evaluation of ex vivo tumor models |
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| المؤلفون: | Rita Mendes, Catarina Brito, Megan C. Cox, Inês A. Isidro, Kathleen Halwachs, Fernanda Silva, Julie J Purkal, Adelyn L Zelaya-Lazo, Ana Félix, Erwin R. Boghaert, Teresa F. Mendes |
| المساهمون: | 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) |
| المصدر: | Scientific Reports, Vol 11, Iss 1, Pp 1-14 (2021) Scientific Reports Repositório Científico de Acesso Aberto de Portugal Repositório Científico de Acesso Aberto de Portugal (RCAAP) instacron:RCAAP |
| بيانات النشر: | Nature Portfolio, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Cancer microenvironment, Science, Drug development, Antineoplastic Agents, Article, 03 medical and health sciences, chemistry.chemical_compound, Mice, 0302 clinical medicine, Lactate dehydrogenase, Cell Line, Tumor, Neoplasms, Spheroids, Cellular, Drug Discovery, Tumor Cells, Cultured, Medicine, Animals, Humans, General, Cancer models, 030304 developmental biology, 0303 health sciences, Multidisciplinary, L-Lactate Dehydrogenase, business.industry, Culture growth, 3. Good health, Clinical trial, chemistry, 030220 oncology & carcinogenesis, Cancer research, Drug Screening Assays, Antitumor, business, Ex vivo |
| الوصف: | 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). 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. publishersversion published |
| اللغة: | English |
| تدمد: | 2045-2322 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6d8ac81b3c771941eb41563f083c9b56Test https://doaj.org/article/6ba6021cf4734f4ebc89722a5ae55c02Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....6d8ac81b3c771941eb41563f083c9b56 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
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