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.
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.
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