Radioiodine (131 1) targets thyroid tissues and has been an effective and standard treatment for differentiated thyroid cancers for many years. However, the Na +/| symporter (NIS), which mediates active iodide uptake into thyroid follicular cells, is also abundantly expressed in salivary ductal cells. Accordingly, many I-treated thyroid cancer survivors suffer from life-long morbidity of l-induced salivary gland (SG) dysfunction, including recurrent sialadenitis, persistent xerostomia, and progressive susceptibility to dental caries and periodontal disease. In this proposal, we aim to explore novel approaches to prevent I-induced SG damage in thyroid cancer patients, and to identify protective saliva biomarkers for patients'susceptibility to progressive I-induced SG dysfunction.
Two specific aims are identified: (1) Transient silencing/inhibition of salivary NIS to eliminate salivary """"""""^1 accumulation during radioiodine therapy;and (2) Identify protective saliva biomarkers and underlying pathobiology for I-induced SG dysfunction. Upon successful completion of the proposed studies, our novel prevention strategy promises to eliminate I-induced SG damage or at least dramatically reduce its occurrence among thyroid cancer survivors who will receive I therapy. We will be able to use quantifiable saliva biomarkers or SG anatomic changes to monitor the onset and progression of SG dysfunction induced by """"""""^1 such that personalized intervention strategies can be applied to patients in a timely manner. We will determine whether saliva biomarkers detected in the early stage of salivary dysfunction induced by I are predictive of future progression to chronic disease. We may also distinguish patients who are more susceptible or resistant to develop life-long morbidity of I-induced SG dysfunction for differential clinical management.

Public Health Relevance

Many thyroid cancer survivors treated with radioiodine suffer from life-long morbidity of 1-131 induced salivary gland dysfunction. The major goal of this proposal is to identify saliva biomarkers enabling personalized intervention of this adverse effect. In addition, we propose a novel prevention strategy with the hope to eliminate radioiodine induced salivary gland damage or at least dramatically reduce its occurrence among thyroid cancer patients treated with radioiodine.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
5P50CA168505-02
Application #
8764986
Study Section
Special Emphasis Panel (ZCA1-RPRB-7)
Project Start
Project End
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
2
Fiscal Year
2014
Total Cost
$303,201
Indirect Cost
$81,214
Name
Ohio State University
Department
Type
DUNS #
832127323
City
Columbus
State
OH
Country
United States
Zip Code
43210
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