Cisplatin induced sensory neuropathy is prevented by vascular endothelial growth factor-A

Increased patient survival is a mark of modern anti-cancer therapy success. Unfortunately treatment side-effects such as neurotoxicity are a major long term concern. Sensory neuropathy is one of the common toxicities that can arise during platinum based chemotherapy. In many cases the current poor u...

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Main Authors: Vencappa, Samanta, Donaldson, Lucy F., Hulse, Richard P.
Format: Article
Published: E-Century Publishing 2015
Online Access:https://eprints.nottingham.ac.uk/50551/
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author Vencappa, Samanta
Donaldson, Lucy F.
Hulse, Richard P.
author_facet Vencappa, Samanta
Donaldson, Lucy F.
Hulse, Richard P.
author_sort Vencappa, Samanta
building Nottingham Research Data Repository
collection Online Access
description Increased patient survival is a mark of modern anti-cancer therapy success. Unfortunately treatment side-effects such as neurotoxicity are a major long term concern. Sensory neuropathy is one of the common toxicities that can arise during platinum based chemotherapy. In many cases the current poor understanding of the neurological degeneration and lack of suitable analgesia has led to high incidences of patient drop out of treatment. VEGF-A is a prominent neuroprotective agent thus it was hypothesised to prevent cisplatin induced neuropathy. Systemic cisplatin treatment (lasting 3 weeks biweekly) resulted in mechanical allodynia and heat hyperalgesia in mice when compared to vehicle control. PGP9.5 sensory nerve fibre innervation was reduced in the plantar skin in the cisplatin treated group versus vehicle control mice. The cisplatin induced sensory neurodegeneration was associated with increased cleaved caspase 3 expression as well as a reduction in Activating Transcription Factor 3 and panVEGF-A expression in sensory neurons. VEGF-A165b expression was unaltered between vehicle and cisplatin treatment. rhVEGF-A165a and rhVEGF-A165b both prevented cisplatin induced sensory neurodegeneration. Cisplatin exposure blunts the regenerative properties of sensory neurons thus leading to sensory neuropathy. However, here it is identified that administration of VEGF-A isoform subtypes induce regeneration and prevent cell death and are therefore a possible adjunct therapy for chemotherapy induced neuropathy.
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spelling nottingham-505512020-05-04T17:09:47Z https://eprints.nottingham.ac.uk/50551/ Cisplatin induced sensory neuropathy is prevented by vascular endothelial growth factor-A Vencappa, Samanta Donaldson, Lucy F. Hulse, Richard P. Increased patient survival is a mark of modern anti-cancer therapy success. Unfortunately treatment side-effects such as neurotoxicity are a major long term concern. Sensory neuropathy is one of the common toxicities that can arise during platinum based chemotherapy. In many cases the current poor understanding of the neurological degeneration and lack of suitable analgesia has led to high incidences of patient drop out of treatment. VEGF-A is a prominent neuroprotective agent thus it was hypothesised to prevent cisplatin induced neuropathy. Systemic cisplatin treatment (lasting 3 weeks biweekly) resulted in mechanical allodynia and heat hyperalgesia in mice when compared to vehicle control. PGP9.5 sensory nerve fibre innervation was reduced in the plantar skin in the cisplatin treated group versus vehicle control mice. The cisplatin induced sensory neurodegeneration was associated with increased cleaved caspase 3 expression as well as a reduction in Activating Transcription Factor 3 and panVEGF-A expression in sensory neurons. VEGF-A165b expression was unaltered between vehicle and cisplatin treatment. rhVEGF-A165a and rhVEGF-A165b both prevented cisplatin induced sensory neurodegeneration. Cisplatin exposure blunts the regenerative properties of sensory neurons thus leading to sensory neuropathy. However, here it is identified that administration of VEGF-A isoform subtypes induce regeneration and prevent cell death and are therefore a possible adjunct therapy for chemotherapy induced neuropathy. E-Century Publishing 2015-06-30 Article PeerReviewed Vencappa, Samanta, Donaldson, Lucy F. and Hulse, Richard P. (2015) Cisplatin induced sensory neuropathy is prevented by vascular endothelial growth factor-A. American Journal of Translational Research, 7 (6). pp. 1032-1044. ISSN 1943-8141 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4532737/
spellingShingle Vencappa, Samanta
Donaldson, Lucy F.
Hulse, Richard P.
Cisplatin induced sensory neuropathy is prevented by vascular endothelial growth factor-A
title Cisplatin induced sensory neuropathy is prevented by vascular endothelial growth factor-A
title_full Cisplatin induced sensory neuropathy is prevented by vascular endothelial growth factor-A
title_fullStr Cisplatin induced sensory neuropathy is prevented by vascular endothelial growth factor-A
title_full_unstemmed Cisplatin induced sensory neuropathy is prevented by vascular endothelial growth factor-A
title_short Cisplatin induced sensory neuropathy is prevented by vascular endothelial growth factor-A
title_sort cisplatin induced sensory neuropathy is prevented by vascular endothelial growth factor-a
url https://eprints.nottingham.ac.uk/50551/
https://eprints.nottingham.ac.uk/50551/