Automated monitoring of respiratory rate as a novel humane endpoint: A refinement in mouse metastatic lung cancer models.

In oncology research, while xenograft tumor models are easily visualized and humane endpoints can be clearly defined, metastatic tumor models are often based on more subjective clinical observations as endpoints. This study aimed at identifying objective non-invasive criteria for predicting imminent...

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Autores principales: Caroline B Winn, Seo-Kyoung Hwang, Jeffrey Morin, Crystal T Bluette, Balasubramanian Manickam, Ziyue K Jiang, Anand Giddabasappa, Chang-Ning Liu, Kristin Matthews
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Publicado: Public Library of Science (PLoS) 2021
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Acceso en línea:https://doaj.org/article/ffeb8f26e92e49e0b6b88f71e8149d0f
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spelling oai:doaj.org-article:ffeb8f26e92e49e0b6b88f71e8149d0f2021-12-02T20:08:09ZAutomated monitoring of respiratory rate as a novel humane endpoint: A refinement in mouse metastatic lung cancer models.1932-620310.1371/journal.pone.0257694https://doaj.org/article/ffeb8f26e92e49e0b6b88f71e8149d0f2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0257694https://doaj.org/toc/1932-6203In oncology research, while xenograft tumor models are easily visualized and humane endpoints can be clearly defined, metastatic tumor models are often based on more subjective clinical observations as endpoints. This study aimed at identifying objective non-invasive criteria for predicting imminent distress and mortality in metastatic lung tumor-bearing mice. BALB/c and C57BL/6 mice were inoculated with CT26 or B16F10 cells, respectively. The mice were housed in Vium smart cages to continuously monitor and stream respiratory rate and locomotion for up to 28 days until scheduled euthanasia or humane endpoint criteria were met. Body weight and body temperature were measured during the study. On days 11, 14, 17 and 28, lungs of subsets of animals were microCT imaged in vivo to assess lung metastasis progression and then euthanized for lung microscopic evaluations. Beginning at day 21, most tumor-bearing animals developed increased respiratory rates followed by decreased locomotion 1-2 days later, compared with the baseline values. Increases in respiratory rate did not correlate to surface tumor nodule counts or lung weight. Body weight measurement did not show significant changes from days 14-28 in either tumor-bearing or control animals. We propose that increases in respiratory rate (1.3-1.5 X) can be used to provide an objective benchmark to signal the need for increased clinical observations or euthanasia. Adoption of this novel humane endpoint criterion would allow investigators time to collect tissue samples prior to spontaneous morbidity or death and significantly reduce the distress of mice in the terminal stages of these metastatic lung tumor models.Caroline B WinnSeo-Kyoung HwangJeffrey MorinCrystal T BluetteBalasubramanian ManickamZiyue K JiangAnand GiddabasappaChang-Ning LiuKristin MatthewsPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 9, p e0257694 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Caroline B Winn
Seo-Kyoung Hwang
Jeffrey Morin
Crystal T Bluette
Balasubramanian Manickam
Ziyue K Jiang
Anand Giddabasappa
Chang-Ning Liu
Kristin Matthews
Automated monitoring of respiratory rate as a novel humane endpoint: A refinement in mouse metastatic lung cancer models.
description In oncology research, while xenograft tumor models are easily visualized and humane endpoints can be clearly defined, metastatic tumor models are often based on more subjective clinical observations as endpoints. This study aimed at identifying objective non-invasive criteria for predicting imminent distress and mortality in metastatic lung tumor-bearing mice. BALB/c and C57BL/6 mice were inoculated with CT26 or B16F10 cells, respectively. The mice were housed in Vium smart cages to continuously monitor and stream respiratory rate and locomotion for up to 28 days until scheduled euthanasia or humane endpoint criteria were met. Body weight and body temperature were measured during the study. On days 11, 14, 17 and 28, lungs of subsets of animals were microCT imaged in vivo to assess lung metastasis progression and then euthanized for lung microscopic evaluations. Beginning at day 21, most tumor-bearing animals developed increased respiratory rates followed by decreased locomotion 1-2 days later, compared with the baseline values. Increases in respiratory rate did not correlate to surface tumor nodule counts or lung weight. Body weight measurement did not show significant changes from days 14-28 in either tumor-bearing or control animals. We propose that increases in respiratory rate (1.3-1.5 X) can be used to provide an objective benchmark to signal the need for increased clinical observations or euthanasia. Adoption of this novel humane endpoint criterion would allow investigators time to collect tissue samples prior to spontaneous morbidity or death and significantly reduce the distress of mice in the terminal stages of these metastatic lung tumor models.
format article
author Caroline B Winn
Seo-Kyoung Hwang
Jeffrey Morin
Crystal T Bluette
Balasubramanian Manickam
Ziyue K Jiang
Anand Giddabasappa
Chang-Ning Liu
Kristin Matthews
author_facet Caroline B Winn
Seo-Kyoung Hwang
Jeffrey Morin
Crystal T Bluette
Balasubramanian Manickam
Ziyue K Jiang
Anand Giddabasappa
Chang-Ning Liu
Kristin Matthews
author_sort Caroline B Winn
title Automated monitoring of respiratory rate as a novel humane endpoint: A refinement in mouse metastatic lung cancer models.
title_short Automated monitoring of respiratory rate as a novel humane endpoint: A refinement in mouse metastatic lung cancer models.
title_full Automated monitoring of respiratory rate as a novel humane endpoint: A refinement in mouse metastatic lung cancer models.
title_fullStr Automated monitoring of respiratory rate as a novel humane endpoint: A refinement in mouse metastatic lung cancer models.
title_full_unstemmed Automated monitoring of respiratory rate as a novel humane endpoint: A refinement in mouse metastatic lung cancer models.
title_sort automated monitoring of respiratory rate as a novel humane endpoint: a refinement in mouse metastatic lung cancer models.
publisher Public Library of Science (PLoS)
publishDate 2021
url https://doaj.org/article/ffeb8f26e92e49e0b6b88f71e8149d0f
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