Suppression of radiation-induced salivary gland dysfunction by IGF-1.

Radiation is a primary or secondary therapeutic modality for treatment of head and neck cancer. A common side effect of irradiation to the neck and neck region is xerostomia caused by salivary gland dysfunction. Approximately 40,000 new cases of xerostomia result from radiation treatment in the Unit...

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Main Authors: Kirsten H Limesand, Sherif Said, Steven M Anderson
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2009-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC2646143?pdf=render
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spelling doaj-bbacecd6716a465a8d2b71bfb7ccb17f2020-11-25T01:48:33ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-01-0143e466310.1371/journal.pone.0004663Suppression of radiation-induced salivary gland dysfunction by IGF-1.Kirsten H LimesandSherif SaidSteven M AndersonRadiation is a primary or secondary therapeutic modality for treatment of head and neck cancer. A common side effect of irradiation to the neck and neck region is xerostomia caused by salivary gland dysfunction. Approximately 40,000 new cases of xerostomia result from radiation treatment in the United States each year. The ensuing salivary gland hypofunction results in significant morbidity and diminishes the effectiveness of anti-cancer therapies as well as the quality of life for these patients. Previous studies in a rat model have shown no correlation between induction of apoptosis in the salivary gland and either the immediate or chronic decrease in salivary function following gamma-radiation treatment.A significant level of apoptosis can be detected in the salivary glands of FVB mice following gamma-radiation treatment of the head and neck and this apoptosis is suppressed in transgenic mice expressing an activated mutant of Akt (myr-Akt1). Importantly, this suppression of apoptosis in myr-Akt1 mice preserves salivary function, as measured by saliva output, three and thirty days after gamma-radiation treatment. In order to translate these studies into a preclinal model we found that intravenous injection of IGF1 stimulated activation of endogenous Akt in the salivary glands in vivo. A single injection of IGF1 prior to exposure to gamma-radiation diminishes salivary acinar cell apoptosis and completely preserves salivary gland function three and thirty days following irradiation.These studies suggest that apoptosis of salivary acinar cells underlies salivary gland hypofunction occurring secondary to radiation of the head and neck region. Targeted delivery of IGF1 to the salivary gland of patients receiving head and neck irradiation may be useful in reducing or eliminating xerostomia and restoring quality of life to these patients.http://europepmc.org/articles/PMC2646143?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Kirsten H Limesand
Sherif Said
Steven M Anderson
spellingShingle Kirsten H Limesand
Sherif Said
Steven M Anderson
Suppression of radiation-induced salivary gland dysfunction by IGF-1.
PLoS ONE
author_facet Kirsten H Limesand
Sherif Said
Steven M Anderson
author_sort Kirsten H Limesand
title Suppression of radiation-induced salivary gland dysfunction by IGF-1.
title_short Suppression of radiation-induced salivary gland dysfunction by IGF-1.
title_full Suppression of radiation-induced salivary gland dysfunction by IGF-1.
title_fullStr Suppression of radiation-induced salivary gland dysfunction by IGF-1.
title_full_unstemmed Suppression of radiation-induced salivary gland dysfunction by IGF-1.
title_sort suppression of radiation-induced salivary gland dysfunction by igf-1.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2009-01-01
description Radiation is a primary or secondary therapeutic modality for treatment of head and neck cancer. A common side effect of irradiation to the neck and neck region is xerostomia caused by salivary gland dysfunction. Approximately 40,000 new cases of xerostomia result from radiation treatment in the United States each year. The ensuing salivary gland hypofunction results in significant morbidity and diminishes the effectiveness of anti-cancer therapies as well as the quality of life for these patients. Previous studies in a rat model have shown no correlation between induction of apoptosis in the salivary gland and either the immediate or chronic decrease in salivary function following gamma-radiation treatment.A significant level of apoptosis can be detected in the salivary glands of FVB mice following gamma-radiation treatment of the head and neck and this apoptosis is suppressed in transgenic mice expressing an activated mutant of Akt (myr-Akt1). Importantly, this suppression of apoptosis in myr-Akt1 mice preserves salivary function, as measured by saliva output, three and thirty days after gamma-radiation treatment. In order to translate these studies into a preclinal model we found that intravenous injection of IGF1 stimulated activation of endogenous Akt in the salivary glands in vivo. A single injection of IGF1 prior to exposure to gamma-radiation diminishes salivary acinar cell apoptosis and completely preserves salivary gland function three and thirty days following irradiation.These studies suggest that apoptosis of salivary acinar cells underlies salivary gland hypofunction occurring secondary to radiation of the head and neck region. Targeted delivery of IGF1 to the salivary gland of patients receiving head and neck irradiation may be useful in reducing or eliminating xerostomia and restoring quality of life to these patients.
url http://europepmc.org/articles/PMC2646143?pdf=render
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