Insulin-like growth factor-1 preserves salivary gland function after fractionated radiation

Kirsten Limesand, Jennifer L. Avila, Kerton Victory, Hui Hua Chang, Yoon Joo Shin, Oliver Grundmann, Rob R. Klein

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Purpose: Radiotherapy for head-and-neck cancer consists of fractionated radiation treatments that cause significant damage to salivary glands leading to chronic salivary gland dysfunction with only limited prevention and treatment options currently available. This study examines the feasibility of IGF-1 in preserving salivary gland function following a fractionated radiation treatment regimen in a pre-clinical model. Methods and Materials: Mice were exposed to fractionated radiation, and salivary gland function and histological analyses of structure, apoptosis, and proliferation were evaluated. Results: In this study, we report that treatment with fractionated doses of radiation results in a significant level of apoptotic cells in FVB mice after each fraction, which is significantly decreased in transgenic mice expressing a constitutively active mutant of Akt1 (myr-Akt1). Salivary gland function is significantly reduced in FVB mice exposed to fractionated radiation; however, myr-Akt1 transgenic mice maintain salivary function under the same treatment conditions. Injection into FVB mice of recombinant insulin-like growth factor-1 (IGF-1), which activates endogenous Akt, suppressed acute apoptosis and preserved salivary gland function after fractionated doses of radiation 30 to 90 days after treatment. FVB mice exposed to fractionated radiation had significantly lower levels of proliferating cell nuclear antigen-positive salivary acinar cells 90 days after treatment, which correlated with a chronic loss of function. In contrast, FVB mice injected with IGF-1 before each radiation treatment exhibited acinar cell proliferation rates similar to those of untreated controls. Conclusion: These studies suggest that activation of IGF-1-mediated pathways before head-and-neck radiation could modulate radiation-induced salivary gland dysfunction and maintain glandular homeostasis.

Original languageEnglish (US)
Pages (from-to)579-586
Number of pages8
JournalInternational Journal of Radiation Oncology Biology Physics
Volume78
Issue number2
DOIs
StatePublished - Oct 1 2010

Fingerprint

salivary glands
insulin
Somatomedins
Salivary Glands
mice
Radiation
radiation
Acinar Cells
apoptosis
Therapeutics
Transgenic Mice
Apoptosis
homeostasis
dosage
Proliferating Cell Nuclear Antigen
Feasibility Studies
antigens
Head and Neck Neoplasms
preserving
radiation therapy

Keywords

  • Akt
  • apoptosis
  • IGF-1
  • salivary gland dysfunction
  • xerostomia

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation
  • Cancer Research
  • Medicine(all)

Cite this

Insulin-like growth factor-1 preserves salivary gland function after fractionated radiation. / Limesand, Kirsten; Avila, Jennifer L.; Victory, Kerton; Chang, Hui Hua; Shin, Yoon Joo; Grundmann, Oliver; Klein, Rob R.

In: International Journal of Radiation Oncology Biology Physics, Vol. 78, No. 2, 01.10.2010, p. 579-586.

Research output: Contribution to journalArticle

Limesand, Kirsten ; Avila, Jennifer L. ; Victory, Kerton ; Chang, Hui Hua ; Shin, Yoon Joo ; Grundmann, Oliver ; Klein, Rob R. / Insulin-like growth factor-1 preserves salivary gland function after fractionated radiation. In: International Journal of Radiation Oncology Biology Physics. 2010 ; Vol. 78, No. 2. pp. 579-586.
@article{9c5b366783f6458899855c474c7028b2,
title = "Insulin-like growth factor-1 preserves salivary gland function after fractionated radiation",
abstract = "Purpose: Radiotherapy for head-and-neck cancer consists of fractionated radiation treatments that cause significant damage to salivary glands leading to chronic salivary gland dysfunction with only limited prevention and treatment options currently available. This study examines the feasibility of IGF-1 in preserving salivary gland function following a fractionated radiation treatment regimen in a pre-clinical model. Methods and Materials: Mice were exposed to fractionated radiation, and salivary gland function and histological analyses of structure, apoptosis, and proliferation were evaluated. Results: In this study, we report that treatment with fractionated doses of radiation results in a significant level of apoptotic cells in FVB mice after each fraction, which is significantly decreased in transgenic mice expressing a constitutively active mutant of Akt1 (myr-Akt1). Salivary gland function is significantly reduced in FVB mice exposed to fractionated radiation; however, myr-Akt1 transgenic mice maintain salivary function under the same treatment conditions. Injection into FVB mice of recombinant insulin-like growth factor-1 (IGF-1), which activates endogenous Akt, suppressed acute apoptosis and preserved salivary gland function after fractionated doses of radiation 30 to 90 days after treatment. FVB mice exposed to fractionated radiation had significantly lower levels of proliferating cell nuclear antigen-positive salivary acinar cells 90 days after treatment, which correlated with a chronic loss of function. In contrast, FVB mice injected with IGF-1 before each radiation treatment exhibited acinar cell proliferation rates similar to those of untreated controls. Conclusion: These studies suggest that activation of IGF-1-mediated pathways before head-and-neck radiation could modulate radiation-induced salivary gland dysfunction and maintain glandular homeostasis.",
keywords = "Akt, apoptosis, IGF-1, salivary gland dysfunction, xerostomia",
author = "Kirsten Limesand and Avila, {Jennifer L.} and Kerton Victory and Chang, {Hui Hua} and Shin, {Yoon Joo} and Oliver Grundmann and Klein, {Rob R.}",
year = "2010",
month = "10",
day = "1",
doi = "10.1016/j.ijrobp.2010.03.035",
language = "English (US)",
volume = "78",
pages = "579--586",
journal = "International Journal of Radiation Oncology Biology Physics",
issn = "0360-3016",
publisher = "Elsevier Inc.",
number = "2",

}

TY - JOUR

T1 - Insulin-like growth factor-1 preserves salivary gland function after fractionated radiation

AU - Limesand, Kirsten

AU - Avila, Jennifer L.

AU - Victory, Kerton

AU - Chang, Hui Hua

AU - Shin, Yoon Joo

AU - Grundmann, Oliver

AU - Klein, Rob R.

PY - 2010/10/1

Y1 - 2010/10/1

N2 - Purpose: Radiotherapy for head-and-neck cancer consists of fractionated radiation treatments that cause significant damage to salivary glands leading to chronic salivary gland dysfunction with only limited prevention and treatment options currently available. This study examines the feasibility of IGF-1 in preserving salivary gland function following a fractionated radiation treatment regimen in a pre-clinical model. Methods and Materials: Mice were exposed to fractionated radiation, and salivary gland function and histological analyses of structure, apoptosis, and proliferation were evaluated. Results: In this study, we report that treatment with fractionated doses of radiation results in a significant level of apoptotic cells in FVB mice after each fraction, which is significantly decreased in transgenic mice expressing a constitutively active mutant of Akt1 (myr-Akt1). Salivary gland function is significantly reduced in FVB mice exposed to fractionated radiation; however, myr-Akt1 transgenic mice maintain salivary function under the same treatment conditions. Injection into FVB mice of recombinant insulin-like growth factor-1 (IGF-1), which activates endogenous Akt, suppressed acute apoptosis and preserved salivary gland function after fractionated doses of radiation 30 to 90 days after treatment. FVB mice exposed to fractionated radiation had significantly lower levels of proliferating cell nuclear antigen-positive salivary acinar cells 90 days after treatment, which correlated with a chronic loss of function. In contrast, FVB mice injected with IGF-1 before each radiation treatment exhibited acinar cell proliferation rates similar to those of untreated controls. Conclusion: These studies suggest that activation of IGF-1-mediated pathways before head-and-neck radiation could modulate radiation-induced salivary gland dysfunction and maintain glandular homeostasis.

AB - Purpose: Radiotherapy for head-and-neck cancer consists of fractionated radiation treatments that cause significant damage to salivary glands leading to chronic salivary gland dysfunction with only limited prevention and treatment options currently available. This study examines the feasibility of IGF-1 in preserving salivary gland function following a fractionated radiation treatment regimen in a pre-clinical model. Methods and Materials: Mice were exposed to fractionated radiation, and salivary gland function and histological analyses of structure, apoptosis, and proliferation were evaluated. Results: In this study, we report that treatment with fractionated doses of radiation results in a significant level of apoptotic cells in FVB mice after each fraction, which is significantly decreased in transgenic mice expressing a constitutively active mutant of Akt1 (myr-Akt1). Salivary gland function is significantly reduced in FVB mice exposed to fractionated radiation; however, myr-Akt1 transgenic mice maintain salivary function under the same treatment conditions. Injection into FVB mice of recombinant insulin-like growth factor-1 (IGF-1), which activates endogenous Akt, suppressed acute apoptosis and preserved salivary gland function after fractionated doses of radiation 30 to 90 days after treatment. FVB mice exposed to fractionated radiation had significantly lower levels of proliferating cell nuclear antigen-positive salivary acinar cells 90 days after treatment, which correlated with a chronic loss of function. In contrast, FVB mice injected with IGF-1 before each radiation treatment exhibited acinar cell proliferation rates similar to those of untreated controls. Conclusion: These studies suggest that activation of IGF-1-mediated pathways before head-and-neck radiation could modulate radiation-induced salivary gland dysfunction and maintain glandular homeostasis.

KW - Akt

KW - apoptosis

KW - IGF-1

KW - salivary gland dysfunction

KW - xerostomia

UR - http://www.scopus.com/inward/record.url?scp=84755161678&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84755161678&partnerID=8YFLogxK

U2 - 10.1016/j.ijrobp.2010.03.035

DO - 10.1016/j.ijrobp.2010.03.035

M3 - Article

C2 - 20638195

AN - SCOPUS:84755161678

VL - 78

SP - 579

EP - 586

JO - International Journal of Radiation Oncology Biology Physics

JF - International Journal of Radiation Oncology Biology Physics

SN - 0360-3016

IS - 2

ER -