The incidence of thyroid cancer is rising at the second fastest rate of all malignancies in the United States and has an increasing tumor-specific mortality annually, making it an important public health problem. The reasons for this increasing incidence and rising death rate are uncertain. The goal of the P01 application is to address the key issues relating to thyroid cancer predisposition, tumorigenesis, and progression in order to enhance the potential for both early diagnosis and the effective treatment of progressive disease. Based on extensive preliminary data from our group, we propose to: (1) examine and identify predisposing genes for papillary thyroid cancer, (2) determine the critical changes responsible for the development of follicular thyroid cancer in an inherited form of the disease, Cowden syndrome, using a novel animal model, and translate this into a scheme to enhance preoperative diagnosis of this form of thyroid cancer, (3) evaluate and identify the key mechanisms of thyroid cancer induction and dedifferentiation induced by the RET/PTC 1 oncogene, one of the most common genetic abnormalities in papillary thyroid cancer, using a second novel animal model system, and (4) determine key pathways involved in tumor invasion and motility for both follicular and papillary thyroid cancers focusing on the models developed in this P01, and then test novel agents directed at blocking these pathway in vitro and in vivo. Over the past six years, the PI's of the individual projects, and the leaders of the cores have created an environment to successfully perform this integrated P01 that is unique for thyroid cancer. This includes a substantial database, integration with pathology, and a record of successful collaborative genetics, laboratory, drug development, and clinical research as evidenced by approximately thirty co-authored publications. Thus, this P01 represents an integrated Bedside-to-Bench-to-Bedside approach targeting the key clinical issues confronting the diagnosis and management of patients with thyroid cancer.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
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Special Emphasis Panel (ZCA1-GRB-S (O1))
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Snyderwine, Elizabeth G
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Ohio State University
Internal Medicine/Medicine
Schools of Medicine
United States
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Chakedis, Jeffery; Shirley, Lawrence A; Terando, Alicia M et al. (2018) Identification of the Thoracic Duct Using Indocyanine Green During Cervical Lymphadenectomy. Ann Surg Oncol 25:3711-3717
Saporito, Donika; Brock, Pamela; Hampel, Heather et al. (2018) Penetrance of a rare familial mutation predisposing to papillary thyroid cancer. Fam Cancer 17:431-434
Segkos, Konstantinos; Porter, Kyle; Senter, Leigha et al. (2018) Neck Ultrasound in Patients with Follicular Thyroid Carcinoma. Horm Cancer 9:433-439
Kotlarek, Marta; Kubiak, Anna; Czetwerty?ska, Ma?gorzata et al. (2018) The rs2910164 Genetic Variant of miR-146a-3p Is Associated with Increased Overall Mortality in Patients with Follicular Variant Papillary Thyroid Carcinoma. Int J Mol Sci 19:
Russart, Kathryn L G; Huk, Danielle; Nelson, Randy J et al. (2018) Elevated aggressive behavior in male mice with thyroid-specific Prkar1a and global Epac1 gene deletion. Horm Behav 98:121-129
Ashtekar, Amruta; Huk, Danielle; Magner, Alexa et al. (2018) Alterations in Sod2-Induced Oxidative Stress Affect Endocrine Cancer Progression. J Clin Endocrinol Metab 103:4135-4145
Smith, Iris Nira; Thacker, Stetson; Jaini, Ritika et al. (2018) Dynamics and structural stability effects of germline PTEN mutations associated with cancer versus autism phenotypes. J Biomol Struct Dyn :1-17
Feng, Fang; Yehia, Lamis; Ni, Ying et al. (2018) A Nonpump Function of Sodium Iodide Symporter in Thyroid Cancer via Cross-talk with PTEN Signaling. Cancer Res 78:6121-6133
Byrd, Victoria; Getz, Ted; Padmanabhan, Roshan et al. (2018) The microbiome in PTEN hamartoma tumor syndrome. Endocr Relat Cancer 25:233-243
Yehia, Lamis; Jindal, Supriya; Komar, Anton A et al. (2018) Non-canonical role of cancer-associated mutant SEC23B in the ribosome biogenesis pathway. Hum Mol Genet 27:3154-3164

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