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DNA damage response and DNA repair – dog as a model?

BACKGROUND: Companion animals like dogs frequently develop tumors with age and similarly to human malignancies, display interpatient tumoral heterogeneity. Tumors are frequently characterized with regard to their mutation spectra, changes in gene expression or protein levels. Among others, these cha...

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Autores principales: Grosse, Nicole, van Loon, Barbara, Rohrer Bley, Carla
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3995094/
https://www.ncbi.nlm.nih.gov/pubmed/24641873
http://dx.doi.org/10.1186/1471-2407-14-203
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author Grosse, Nicole
van Loon, Barbara
Rohrer Bley, Carla
author_facet Grosse, Nicole
van Loon, Barbara
Rohrer Bley, Carla
author_sort Grosse, Nicole
collection PubMed
description BACKGROUND: Companion animals like dogs frequently develop tumors with age and similarly to human malignancies, display interpatient tumoral heterogeneity. Tumors are frequently characterized with regard to their mutation spectra, changes in gene expression or protein levels. Among others, these changes affect proteins involved in the DNA damage response (DDR), which served as a basis for the development of numerous clinically relevant cancer therapies. Even though the effects of different DNA damaging agents, as well as DDR kinetics, have been well characterized in mammalian cells in vitro, very little is so far known about the kinetics of DDR in tumor and normal tissues in vivo. DISCUSSION: Due to (i) the similarities between human and canine genomes, (ii) the course of spontaneous tumor development, as well as (iii) common exposure to environmental agents, canine tumors are potentially an excellent model to study DDR in vivo. This is further supported by the fact that dogs show approximately the same rate of tumor development with age as humans. Though similarities between human and dog osteosarcoma, as well as mammary tumors have been well established, only few studies using canine tumor samples addressed the importance of affected DDR pathways in tumor progression, thus leaving many questions unanswered. SUMMARY: Studies in humans showed that misregulated DDR pathways play an important role during tumor development, as well as in treatment response. Since dogs are proposed to be a good tumor model in many aspects of cancer research, we herein critically investigate the current knowledge of canine DDR and discuss (i) its future potential for studies on the in vivo level, as well as (ii) its possible translation to veterinary and human medicine.
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spelling pubmed-39950942014-04-23 DNA damage response and DNA repair – dog as a model? Grosse, Nicole van Loon, Barbara Rohrer Bley, Carla BMC Cancer Debate BACKGROUND: Companion animals like dogs frequently develop tumors with age and similarly to human malignancies, display interpatient tumoral heterogeneity. Tumors are frequently characterized with regard to their mutation spectra, changes in gene expression or protein levels. Among others, these changes affect proteins involved in the DNA damage response (DDR), which served as a basis for the development of numerous clinically relevant cancer therapies. Even though the effects of different DNA damaging agents, as well as DDR kinetics, have been well characterized in mammalian cells in vitro, very little is so far known about the kinetics of DDR in tumor and normal tissues in vivo. DISCUSSION: Due to (i) the similarities between human and canine genomes, (ii) the course of spontaneous tumor development, as well as (iii) common exposure to environmental agents, canine tumors are potentially an excellent model to study DDR in vivo. This is further supported by the fact that dogs show approximately the same rate of tumor development with age as humans. Though similarities between human and dog osteosarcoma, as well as mammary tumors have been well established, only few studies using canine tumor samples addressed the importance of affected DDR pathways in tumor progression, thus leaving many questions unanswered. SUMMARY: Studies in humans showed that misregulated DDR pathways play an important role during tumor development, as well as in treatment response. Since dogs are proposed to be a good tumor model in many aspects of cancer research, we herein critically investigate the current knowledge of canine DDR and discuss (i) its future potential for studies on the in vivo level, as well as (ii) its possible translation to veterinary and human medicine. BioMed Central 2014-03-19 /pmc/articles/PMC3995094/ /pubmed/24641873 http://dx.doi.org/10.1186/1471-2407-14-203 Text en Copyright © 2014 Grosse et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.
spellingShingle Debate
Grosse, Nicole
van Loon, Barbara
Rohrer Bley, Carla
DNA damage response and DNA repair – dog as a model?
title DNA damage response and DNA repair – dog as a model?
title_full DNA damage response and DNA repair – dog as a model?
title_fullStr DNA damage response and DNA repair – dog as a model?
title_full_unstemmed DNA damage response and DNA repair – dog as a model?
title_short DNA damage response and DNA repair – dog as a model?
title_sort dna damage response and dna repair – dog as a model?
topic Debate
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3995094/
https://www.ncbi.nlm.nih.gov/pubmed/24641873
http://dx.doi.org/10.1186/1471-2407-14-203
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