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.
|Liyanarachchi, Sandya; Li, Wei; Yan, Pearlly et al. (2016) Genome-Wide Expression Screening Discloses Long Noncoding RNAs Involved in Thyroid Carcinogenesis. J Clin Endocrinol Metab 101:4005-4013|
|Hollingsworth, Brynn; Senter, Leigha; Zhang, Xiaoli et al. (2016) Risk Factors of (131)I-Induced Salivary Gland Damage in Thyroid Cancer Patients. J Clin Endocrinol Metab 101:4085-4093|
|Justiniano, Steven E; McElroy, Joseph P; Yu, Lianbo et al. (2016) Genetic variants in thyroid cancer distant metastases. Endocr Relat Cancer 23:L33-6|
|Nabhan, Fadi; Ringel, Matthew D (2016) Thyroid nodules and cancer management guidelines: comparisons and controversies. Endocr Relat Cancer :|
|Shirley, Lawrence A; McCarty, Samantha; Yang, Ming-Chen et al. (2016) Integrin-linked kinase affects signaling pathways and migration in thyroid cancer cells and is a potential therapeutic target. Surgery 159:163-70|
|Danysh, Brian P; Rieger, Erin Y; Sinha, Deepankar K et al. (2016) Long-term vemurafenib treatment drives inhibitor resistance through a spontaneous KRAS G12D mutation in a BRAF V600E papillary thyroid carcinoma model. Oncotarget 7:30907-23|
|Nagy, Rebecca; Ringel, Matthew D (2015) Genetic predisposition for nonmedullary thyroid cancer. Horm Cancer 6:13-20|
|Tomsic, Jerneja; He, Huiling; de la Chapelle, Albert (2015) HABP2 Mutation and Nonmedullary Thyroid Cancer. N Engl J Med 373:2086|
|He, Huiling; Li, Wei; Liyanarachchi, Sandya et al. (2015) Multiple functional variants in long-range enhancer elements contribute to the risk of SNP rs965513 in thyroid cancer. Proc Natl Acad Sci U S A 112:6128-33|
|He, Huiling; Li, Wei; Liyanarachchi, Sandya et al. (2015) Genetic predisposition to papillary thyroid carcinoma: involvement of FOXE1, TSHR, and a novel lincRNA gene, PTCSC2. J Clin Endocrinol Metab 100:E164-72|
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