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Rapid in vivo testing of drug response in multiple myeloma made possible by xenograft to turkey embryos

BACKGROUND: The best current xenograft model of multiple myeloma (MM) in immune-deficient non-obese diabetic/severe-combined immunodeficient mice is costly, animal maintenance is complex and several weeks are required to establish engraftment and study drug efficacy. More practical in vivo models ma...

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Autores principales: Farnoushi, Y, Cipok, M, Kay, S, Jan, H, Ohana, A, Naparstek, E, Goldstein, R S, Deutsch, V R
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3242603/
https://www.ncbi.nlm.nih.gov/pubmed/22045188
http://dx.doi.org/10.1038/bjc.2011.445
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author Farnoushi, Y
Cipok, M
Kay, S
Jan, H
Ohana, A
Naparstek, E
Goldstein, R S
Deutsch, V R
author_facet Farnoushi, Y
Cipok, M
Kay, S
Jan, H
Ohana, A
Naparstek, E
Goldstein, R S
Deutsch, V R
author_sort Farnoushi, Y
collection PubMed
description BACKGROUND: The best current xenograft model of multiple myeloma (MM) in immune-deficient non-obese diabetic/severe-combined immunodeficient mice is costly, animal maintenance is complex and several weeks are required to establish engraftment and study drug efficacy. More practical in vivo models may reduce time and drug development cost. We recently described a rapid low-cost xenograft model of human blood malignancies in pre-immune turkey. Here, we report application of this system for studying MM growth and the preclinical assessment of anticancer therapies. METHODS: Cell lines and MM patient cells were injected intravenously into embryonic veins on embryonic day 11 (E11). Engraftment of human cells in haematopoietic organs was detected by quantitative real-time polymerase chain reaction, immunohistochemistry, flow cytometry and circulating free light chain. RESULTS: Engraftment was detected after 1 week in all embryos injected with cell lines and in 50% of those injected with patient cells. Injection of bortezomib or lenalinomide 48 h after cell injection at therapeutic levels that were not toxic to the bone marrow dramatically reduced MM engraftment. CONCLUSION: The turkey embryo provides a practical, xenograft system to study MM and demonstrates the utility of this model for rapid and affordable testing therapeutics in vivo. With further development, this model may enable rapid, inexpensive personalised drug screening.
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spelling pubmed-32426032012-11-22 Rapid in vivo testing of drug response in multiple myeloma made possible by xenograft to turkey embryos Farnoushi, Y Cipok, M Kay, S Jan, H Ohana, A Naparstek, E Goldstein, R S Deutsch, V R Br J Cancer Translational Therapeutics BACKGROUND: The best current xenograft model of multiple myeloma (MM) in immune-deficient non-obese diabetic/severe-combined immunodeficient mice is costly, animal maintenance is complex and several weeks are required to establish engraftment and study drug efficacy. More practical in vivo models may reduce time and drug development cost. We recently described a rapid low-cost xenograft model of human blood malignancies in pre-immune turkey. Here, we report application of this system for studying MM growth and the preclinical assessment of anticancer therapies. METHODS: Cell lines and MM patient cells were injected intravenously into embryonic veins on embryonic day 11 (E11). Engraftment of human cells in haematopoietic organs was detected by quantitative real-time polymerase chain reaction, immunohistochemistry, flow cytometry and circulating free light chain. RESULTS: Engraftment was detected after 1 week in all embryos injected with cell lines and in 50% of those injected with patient cells. Injection of bortezomib or lenalinomide 48 h after cell injection at therapeutic levels that were not toxic to the bone marrow dramatically reduced MM engraftment. CONCLUSION: The turkey embryo provides a practical, xenograft system to study MM and demonstrates the utility of this model for rapid and affordable testing therapeutics in vivo. With further development, this model may enable rapid, inexpensive personalised drug screening. Nature Publishing Group 2011-11-22 2011-11-01 /pmc/articles/PMC3242603/ /pubmed/22045188 http://dx.doi.org/10.1038/bjc.2011.445 Text en Copyright © 2011 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Translational Therapeutics
Farnoushi, Y
Cipok, M
Kay, S
Jan, H
Ohana, A
Naparstek, E
Goldstein, R S
Deutsch, V R
Rapid in vivo testing of drug response in multiple myeloma made possible by xenograft to turkey embryos
title Rapid in vivo testing of drug response in multiple myeloma made possible by xenograft to turkey embryos
title_full Rapid in vivo testing of drug response in multiple myeloma made possible by xenograft to turkey embryos
title_fullStr Rapid in vivo testing of drug response in multiple myeloma made possible by xenograft to turkey embryos
title_full_unstemmed Rapid in vivo testing of drug response in multiple myeloma made possible by xenograft to turkey embryos
title_short Rapid in vivo testing of drug response in multiple myeloma made possible by xenograft to turkey embryos
title_sort rapid in vivo testing of drug response in multiple myeloma made possible by xenograft to turkey embryos
topic Translational Therapeutics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3242603/
https://www.ncbi.nlm.nih.gov/pubmed/22045188
http://dx.doi.org/10.1038/bjc.2011.445
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