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Expression of platelet‐derived growth factor receptor‐α/ß, vascular endothelial growth factor receptor‐2, c‐Abl, and c‐Kit in canine granulomatous meningoencephalitis and necrotizing encephalitis

BACKGROUND: Given the active research on targeted therapy using tyrosine kinase (TK) inhibitors (TKIs) in the field of oncology, further studies have recently been conducted to evaluate their use in autoimmune disorders. Based on immunological investigations, previous studies have suggested that gra...

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Autores principales: Song, Joong‐Hyun, Yu, Do‐Hyeon, Hwang, Tae‐Sung, Seung, Byung‐Joon, Sur, Jung‐Hyang, Kim, Young Joo, Jung, Dong‐In
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738704/
https://www.ncbi.nlm.nih.gov/pubmed/32585777
http://dx.doi.org/10.1002/vms3.314
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author Song, Joong‐Hyun
Yu, Do‐Hyeon
Hwang, Tae‐Sung
Seung, Byung‐Joon
Sur, Jung‐Hyang
Kim, Young Joo
Jung, Dong‐In
author_facet Song, Joong‐Hyun
Yu, Do‐Hyeon
Hwang, Tae‐Sung
Seung, Byung‐Joon
Sur, Jung‐Hyang
Kim, Young Joo
Jung, Dong‐In
author_sort Song, Joong‐Hyun
collection PubMed
description BACKGROUND: Given the active research on targeted therapy using tyrosine kinase (TK) inhibitors (TKIs) in the field of oncology, further studies have recently been conducted to evaluate their use in autoimmune disorders. Based on immunological investigations, previous studies have suggested that granulomatous meningoencephalomyelitis (GME) and necrotizing encephalomyelitis (NE) are similar to multiple sclerosis (MS), which is a human autoimmune demyelinating central nervous system disease. OBJECTIVES: Considering this perspective, we hypothesized that canine GME and NE have significant expression of one or more TKs, which are associated with human MS pathogenesis. METHODS: To determine the possible use of conventional multi‐targeted TKIs as a treatment for canine GME and NE, we characterized the immunohistochemical expression of platelet‐derived growth factor receptor (PDGFR)‐α, PDGFR‐ß, vascular endothelial growth factor receptor (VEGFR)‐2, c‐Abl and c‐Kit in GME and NE samples. RESULTS: Histological samples from four dogs with GME and three with NE were retrieved. All samples stained positive for PDGFR‐ß (7/7 [100%]). PDGFR‐α and c‐Kit were expressed in 3/7 (42.8%) samples each. c‐Abl was identified in 2/7 (28.5%) samples; no sample showed VEGFR‐2 (0%) expression. Co‐expression of TKs was identified in 6/7 (85.7%) dogs. CONCLUSIONS: All samples were positive for at least one or more of PDGFR‐α, PDGFR‐ß, c‐Kit and c‐Abl, which are known as the target TKs of conventional multi‐targeted TKIs. Their presence does suggest that these TKs may play a role in the pathogenesis of GME and NE. Therefore, multi‐targeted TKIs may provide benefits in the treatment of canine GME and NE by suppressing the activity of these TKs.
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spelling pubmed-77387042020-12-18 Expression of platelet‐derived growth factor receptor‐α/ß, vascular endothelial growth factor receptor‐2, c‐Abl, and c‐Kit in canine granulomatous meningoencephalitis and necrotizing encephalitis Song, Joong‐Hyun Yu, Do‐Hyeon Hwang, Tae‐Sung Seung, Byung‐Joon Sur, Jung‐Hyang Kim, Young Joo Jung, Dong‐In Vet Med Sci Original Articles BACKGROUND: Given the active research on targeted therapy using tyrosine kinase (TK) inhibitors (TKIs) in the field of oncology, further studies have recently been conducted to evaluate their use in autoimmune disorders. Based on immunological investigations, previous studies have suggested that granulomatous meningoencephalomyelitis (GME) and necrotizing encephalomyelitis (NE) are similar to multiple sclerosis (MS), which is a human autoimmune demyelinating central nervous system disease. OBJECTIVES: Considering this perspective, we hypothesized that canine GME and NE have significant expression of one or more TKs, which are associated with human MS pathogenesis. METHODS: To determine the possible use of conventional multi‐targeted TKIs as a treatment for canine GME and NE, we characterized the immunohistochemical expression of platelet‐derived growth factor receptor (PDGFR)‐α, PDGFR‐ß, vascular endothelial growth factor receptor (VEGFR)‐2, c‐Abl and c‐Kit in GME and NE samples. RESULTS: Histological samples from four dogs with GME and three with NE were retrieved. All samples stained positive for PDGFR‐ß (7/7 [100%]). PDGFR‐α and c‐Kit were expressed in 3/7 (42.8%) samples each. c‐Abl was identified in 2/7 (28.5%) samples; no sample showed VEGFR‐2 (0%) expression. Co‐expression of TKs was identified in 6/7 (85.7%) dogs. CONCLUSIONS: All samples were positive for at least one or more of PDGFR‐α, PDGFR‐ß, c‐Kit and c‐Abl, which are known as the target TKs of conventional multi‐targeted TKIs. Their presence does suggest that these TKs may play a role in the pathogenesis of GME and NE. Therefore, multi‐targeted TKIs may provide benefits in the treatment of canine GME and NE by suppressing the activity of these TKs. John Wiley and Sons Inc. 2020-06-25 /pmc/articles/PMC7738704/ /pubmed/32585777 http://dx.doi.org/10.1002/vms3.314 Text en © 2020 The Authors. Veterinary Medicine and Science Published by John Wiley & Sons Ltd This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Song, Joong‐Hyun
Yu, Do‐Hyeon
Hwang, Tae‐Sung
Seung, Byung‐Joon
Sur, Jung‐Hyang
Kim, Young Joo
Jung, Dong‐In
Expression of platelet‐derived growth factor receptor‐α/ß, vascular endothelial growth factor receptor‐2, c‐Abl, and c‐Kit in canine granulomatous meningoencephalitis and necrotizing encephalitis
title Expression of platelet‐derived growth factor receptor‐α/ß, vascular endothelial growth factor receptor‐2, c‐Abl, and c‐Kit in canine granulomatous meningoencephalitis and necrotizing encephalitis
title_full Expression of platelet‐derived growth factor receptor‐α/ß, vascular endothelial growth factor receptor‐2, c‐Abl, and c‐Kit in canine granulomatous meningoencephalitis and necrotizing encephalitis
title_fullStr Expression of platelet‐derived growth factor receptor‐α/ß, vascular endothelial growth factor receptor‐2, c‐Abl, and c‐Kit in canine granulomatous meningoencephalitis and necrotizing encephalitis
title_full_unstemmed Expression of platelet‐derived growth factor receptor‐α/ß, vascular endothelial growth factor receptor‐2, c‐Abl, and c‐Kit in canine granulomatous meningoencephalitis and necrotizing encephalitis
title_short Expression of platelet‐derived growth factor receptor‐α/ß, vascular endothelial growth factor receptor‐2, c‐Abl, and c‐Kit in canine granulomatous meningoencephalitis and necrotizing encephalitis
title_sort expression of platelet‐derived growth factor receptor‐α/ß, vascular endothelial growth factor receptor‐2, c‐abl, and c‐kit in canine granulomatous meningoencephalitis and necrotizing encephalitis
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738704/
https://www.ncbi.nlm.nih.gov/pubmed/32585777
http://dx.doi.org/10.1002/vms3.314
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