Insulin-Like Growth Factor–1 Preserves Salivary Gland Function After Fractionated Radiation
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 IG...
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| Published in | International journal of radiation oncology, biology, physics Vol. 78; no. 2; pp. 579 - 586 |
|---|---|
| Main Authors | , , , , , , |
| Format | Journal Article |
| Language | English |
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New York, NY
Elsevier Inc
01.10.2010
Elsevier |
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| 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. |
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| AbstractList | 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.
Mice were exposed to fractionated radiation, and salivary gland function and histological analyses of structure, apoptosis, and proliferation were evaluated.
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.
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. 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. |
| Author | Grundmann, Oliver, Ph.D Avila, Jennifer L., M.S Limesand, Kirsten H., Ph.D Victory, Kerton Shin, Yoon Joo Klein, Rob R., M.D Chang, Hui-Hua |
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| Keywords | apoptosis IGF-1 Akt xerostomia salivary gland dysfunction Biological properties Radioprotector Toxicity Transgenic animal Xerostomia ENT disease Complication Aptyalism Rodentia Akt protein kinase Salivary gland Malignant tumor Insulin like growth factor 1 Radiotherapy Fractionated dose Vertebrata Mammalia Salivary gland disease Treatment Mouse Dysfunction Radiation injury Head and neck cancer Cancer Apoptosis |
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| Snippet | Purpose Radiotherapy for head-and-neck cancer consists of fractionated radiation treatments that cause significant damage to salivary glands leading to chronic... Radiotherapy for head-and-neck cancer consists of fractionated radiation treatments that cause significant damage to salivary glands leading to chronic... Purpose: Radiotherapy for head-and-neck cancer consists of fractionated radiation treatments that cause significant damage to salivary glands leading to... |
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| SubjectTerms | Akt ANIMALS APOPTOSIS Apoptosis - drug effects Biological and medical sciences BODY CELL PROLIFERATION Cell Proliferation - drug effects DISEASES Dose Fractionation Ent and stomatology Feasibility Studies FRACTIONATED IRRADIATION GLANDS GROWTH FACTORS HEAD Hematology, Oncology and Palliative Medicine HOMEOSTASIS HORMONES IGF-1 INSULIN Insulin-Like Growth Factor I - therapeutic use IRRADIATION MAMMALS Medical sciences MEDICINE MICE Mice, Transgenic MITOGENS NECK NEOPLASMS NUCLEAR MEDICINE ORGANIC COMPOUNDS ORGANS Otorhinolaryngology (head neck, general aspects and miscellaneous) Otorhinolaryngology. Stomatology PEPTIDE HORMONES Proliferating Cell Nuclear Antigen - metabolism PROTEINS Proto-Oncogene Proteins c-akt - metabolism Radiation Injuries, Experimental - pathology Radiation Injuries, Experimental - prevention & control Radiation therapy and radiosensitizing agent Radiation-Protective Agents - therapeutic use RADIOLOGY RADIOLOGY AND NUCLEAR MEDICINE RADIOTHERAPY Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects) Recombinant Proteins - metabolism RODENTS salivary gland dysfunction SALIVARY GLANDS Salivary Glands - drug effects Salivary Glands - pathology Salivary Glands - radiation effects THERAPY TRANSGENIC ANIMALS TRANSGENIC MICE Treatment with physical agents Treatment. General aspects Tumors VERTEBRATES xerostomia Xerostomia - etiology Xerostomia - prevention & control |
| Title | Insulin-Like Growth Factor–1 Preserves Salivary Gland Function After Fractionated Radiation |
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