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Modeling the energetic cost of cancer as a result of altered energy metabolism: implications for cachexia

BACKGROUND: Cachexia affects most patients with incurable cancer. We hypothesize that in metastatic cancer the mass of the tumor as well as its level of anaerobic energy metabolism play a critical role in describing its energetic cost, which results in elevated resting energy expenditure and glucose...

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Autores principales: Friesen, Douglas E., Baracos, Vickie E., Tuszynski, Jack A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4570294/
https://www.ncbi.nlm.nih.gov/pubmed/26370269
http://dx.doi.org/10.1186/s12976-015-0015-0
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author Friesen, Douglas E.
Baracos, Vickie E.
Tuszynski, Jack A.
author_facet Friesen, Douglas E.
Baracos, Vickie E.
Tuszynski, Jack A.
author_sort Friesen, Douglas E.
collection PubMed
description BACKGROUND: Cachexia affects most patients with incurable cancer. We hypothesize that in metastatic cancer the mass of the tumor as well as its level of anaerobic energy metabolism play a critical role in describing its energetic cost, which results in elevated resting energy expenditure and glucose utilization, leading to cachexia. Prior models of cancer cachexia may have underestimated the specific energetic cost of cancer as they have not taken the range of tumor mass and anaerobic energy metabolism fully into account. METHODS: We therefore modelled the energetic cost of cancer as a function of the percentage of energy the cancer produces anaerobically, based on resting energy expenditure, glucose turnover, glucose recycling, and oxygen consumption in cancer patients found in previous studies. RESULTS: Data from two clinical studies where tumor burden was estimated and resting energy expenditure or oxygen consumption were measured lead to a broad range of estimates of tumor cost from 190 to 470 kcal/kg tumor/day. These values will vary based of the percentage of energy the cancer produces anaerobically (from 0 to 100 %), which in and of itself can alter the cost over a 2 to 3-fold range. In addition to the tumor cost/kg and the degree of anaerobic metabolism, the impact on a given individual patient will depend on tumor burden, which can exceed 1 kg in advanced metastatic disease. Considering these dimensions of tumor cost we are able to produce a 2-dimensional map of potential values, with an overall range of 100–1400 kcal/day. CONCLUSIONS: Quantifying the energetic cost of cancer may benefit an understanding of the tumor’s causation of cachexia. Our estimates of the range of tumor cost include values that are higher than prior estimates and suggest that in metastatic disease the tumor cost could be expected to eclipse attempts to stabilize energy balance through nutrition support or by drug therapies. Tumor mass and the percentage of anaerobic metabolism in the tumor contribute to the cost of the tumor on the body and potentially lead directly to negative energy balance and increased muscle wasting. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12976-015-0015-0) contains supplementary material, which is available to authorized users.
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spelling pubmed-45702942015-09-16 Modeling the energetic cost of cancer as a result of altered energy metabolism: implications for cachexia Friesen, Douglas E. Baracos, Vickie E. Tuszynski, Jack A. Theor Biol Med Model Research BACKGROUND: Cachexia affects most patients with incurable cancer. We hypothesize that in metastatic cancer the mass of the tumor as well as its level of anaerobic energy metabolism play a critical role in describing its energetic cost, which results in elevated resting energy expenditure and glucose utilization, leading to cachexia. Prior models of cancer cachexia may have underestimated the specific energetic cost of cancer as they have not taken the range of tumor mass and anaerobic energy metabolism fully into account. METHODS: We therefore modelled the energetic cost of cancer as a function of the percentage of energy the cancer produces anaerobically, based on resting energy expenditure, glucose turnover, glucose recycling, and oxygen consumption in cancer patients found in previous studies. RESULTS: Data from two clinical studies where tumor burden was estimated and resting energy expenditure or oxygen consumption were measured lead to a broad range of estimates of tumor cost from 190 to 470 kcal/kg tumor/day. These values will vary based of the percentage of energy the cancer produces anaerobically (from 0 to 100 %), which in and of itself can alter the cost over a 2 to 3-fold range. In addition to the tumor cost/kg and the degree of anaerobic metabolism, the impact on a given individual patient will depend on tumor burden, which can exceed 1 kg in advanced metastatic disease. Considering these dimensions of tumor cost we are able to produce a 2-dimensional map of potential values, with an overall range of 100–1400 kcal/day. CONCLUSIONS: Quantifying the energetic cost of cancer may benefit an understanding of the tumor’s causation of cachexia. Our estimates of the range of tumor cost include values that are higher than prior estimates and suggest that in metastatic disease the tumor cost could be expected to eclipse attempts to stabilize energy balance through nutrition support or by drug therapies. Tumor mass and the percentage of anaerobic metabolism in the tumor contribute to the cost of the tumor on the body and potentially lead directly to negative energy balance and increased muscle wasting. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12976-015-0015-0) contains supplementary material, which is available to authorized users. BioMed Central 2015-09-15 /pmc/articles/PMC4570294/ /pubmed/26370269 http://dx.doi.org/10.1186/s12976-015-0015-0 Text en © Friesen et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Friesen, Douglas E.
Baracos, Vickie E.
Tuszynski, Jack A.
Modeling the energetic cost of cancer as a result of altered energy metabolism: implications for cachexia
title Modeling the energetic cost of cancer as a result of altered energy metabolism: implications for cachexia
title_full Modeling the energetic cost of cancer as a result of altered energy metabolism: implications for cachexia
title_fullStr Modeling the energetic cost of cancer as a result of altered energy metabolism: implications for cachexia
title_full_unstemmed Modeling the energetic cost of cancer as a result of altered energy metabolism: implications for cachexia
title_short Modeling the energetic cost of cancer as a result of altered energy metabolism: implications for cachexia
title_sort modeling the energetic cost of cancer as a result of altered energy metabolism: implications for cachexia
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4570294/
https://www.ncbi.nlm.nih.gov/pubmed/26370269
http://dx.doi.org/10.1186/s12976-015-0015-0
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