دورية أكاديمية
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. |
---|---|
المؤلفون: | Cox MC; AbbVie, 1 North Waukegan Road, North Chicago, IL, 60064-6098, USA., Mendes R; IBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2780-901, Oeiras, Portugal.; Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Avenida da República, 2780-157, Oeiras, Portugal., Silva F; CEDOC-FCM-NOVA, Centro de Estudos de Doenças Crónicas da Faculdade de Ciências Médicas, Universidade Nova de Lisboa, R. Câmara Pestana 6, 1150-078, Lisbon, Portugal., Mendes TF; IBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2780-901, Oeiras, Portugal.; Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Avenida da República, 2780-157, Oeiras, Portugal., Zelaya-Lazo A; AbbVie, 1 North Waukegan Road, North Chicago, IL, 60064-6098, USA., Halwachs K; AbbVie, 1 North Waukegan Road, North Chicago, IL, 60064-6098, USA., Purkal JJ; AbbVie, 1 North Waukegan Road, North Chicago, IL, 60064-6098, USA., Isidro IA; IBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2780-901, Oeiras, Portugal.; Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Avenida da República, 2780-157, Oeiras, Portugal., Félix A; CEDOC-FCM-NOVA, Centro de Estudos de Doenças Crónicas da Faculdade de Ciências Médicas, Universidade Nova de Lisboa, R. Câmara Pestana 6, 1150-078, Lisbon, Portugal.; IPOLFG, Instituto Português de Oncologia de Lisboa Francisco Gentil, R. Prof. Lima Basto, 1099-023, Lisbon, Portugal., Boghaert ER; AbbVie, 1 North Waukegan Road, North Chicago, IL, 60064-6098, USA., Brito C; IBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2780-901, Oeiras, Portugal. anabrito@ibet.pt.; Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Avenida da República, 2780-157, Oeiras, Portugal. anabrito@ibet.pt.; The Discoveries Centre for Regenerative and Precision Medicine, Lisbon Campus, Av. da República, 2780-157, Oeiras, Portugal. anabrito@ibet.pt. |
المصدر: | Scientific reports [Sci Rep] 2021 Sep 17; Vol. 11 (1), pp. 18571. Date of Electronic Publication: 2021 Sep 17. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: London : Nature Publishing Group, copyright 2011- |
مواضيع طبية MeSH: | Drug Screening Assays, Antitumor/*methods , L-Lactate Dehydrogenase/*metabolism , Neoplasms/*drug therapy , Neoplasms/*metabolism, Animals ; Antineoplastic Agents/pharmacology ; Cell Line, Tumor ; Drug Discovery/methods ; Humans ; Mice ; Spheroids, Cellular/drug effects ; Spheroids, Cellular/metabolism ; Tumor Cells, Cultured |
مستخلص: | 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. (© 2021. The Author(s).) |
References: | Int J Mol Sci. 2018 Jan 18;19(1):. (PMID: 29346265) Ann Oncol. 1998 Aug;9(8):885-91. (PMID: 9789612) J Health Econ. 2016 May;47:20-33. (PMID: 26928437) Breast. 2016 Dec;30:92-100. (PMID: 27668856) Cancer Metastasis Rev. 2014 Mar;33(1):17-39. (PMID: 24357056) J Cancer Res Clin Oncol. 2016 Sep;142(9):1955-66. (PMID: 27424189) Trends Pharmacol Sci. 2017 Oct;38(10):852-872. (PMID: 28709554) Sci Rep. 2017 Nov 30;7(1):16645. (PMID: 29192263) Methods Mol Biol. 2013;979:65-70. (PMID: 23397389) Biotechnol J. 2017 Jan;12(1):. (PMID: 27966285) Pharmacol Res Perspect. 2015 Jun;3(3):e00149. (PMID: 26171228) Sci Rep. 2017 Oct 26;7(1):14167. (PMID: 29074857) J Control Release. 2012 Dec 10;164(2):192-204. (PMID: 22613880) Sci Rep. 2016 Jul 01;6:28951. (PMID: 27364600) Biotechnol Bioeng. 1995 May 20;46(4):351-60. (PMID: 18623322) J Biotechnol. 2015 Jul 10;205:70-81. (PMID: 25687101) Pancreatology. 2017 Jan - Feb;17(1):7-12. (PMID: 28034553) Biotechnol J. 2017 Feb;12(2):. (PMID: 28098436) Adv Healthc Mater. 2018 Apr;7(8):e1701174. (PMID: 29350495) Diseases. 2018 Sep 22;6(4):. (PMID: 30249005) Adv Drug Deliv Rev. 2014 Dec 15;79-80:40-9. (PMID: 24996134) PLoS One. 2012;7(9):e45308. (PMID: 23028922) Sci Rep. 2020 Nov 10;10(1):19462. (PMID: 33173111) Nature. 2013 Sep 19;501(7467):346-54. (PMID: 24048067) Nat Methods. 2016 Jun;13(6):521-7. (PMID: 27135972) Biochim Biophys Acta. 2010 Jan;1805(1):105-17. (PMID: 19931353) Ann Oncol. 2003 Dec;14(12):1776-82. (PMID: 14630684) Int J Mol Sci. 2019 Feb 15;20(4):. (PMID: 30781344) SLAS Discov. 2019 Jul;24(6):615-627. (PMID: 30817892) Nat Rev Cancer. 2016 Dec;16(12):759-773. (PMID: 27687979) J Histochem Cytochem. 2005 Jan;53(1):23-34. (PMID: 15637335) Nat Med. 2014 Apr;20(4):342-4. (PMID: 24710377) ACS Biomater Sci Eng. 2015 Oct 12;1(10):877-894. (PMID: 33429520) Future Sci OA. 2017 Mar 27;3(2):FSO190. (PMID: 28670477) Biochem Pharmacol. 2014 Nov 1;92(1):43-54. (PMID: 25168677) BMC Biotechnol. 2009 Sep 22;9:82. (PMID: 19772662) |
المشرفين على المادة: | 0 (Antineoplastic Agents) EC 1.1.1.27 (L-Lactate Dehydrogenase) |
تواريخ الأحداث: | Date Created: 20210918 Date Completed: 20211115 Latest Revision: 20211115 |
رمز التحديث: | 20231215 |
مُعرف محوري في PubMed: | PMC8448883 |
DOI: | 10.1038/s41598-021-97894-0 |
PMID: | 34535719 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2045-2322 |
---|---|
DOI: | 10.1038/s41598-021-97894-0 |