UCSF DIABETES, ENDOCRINOLOGY & METABOLISM TRAINING PROGRAM FACULTY RESEARCH SUMMARIES
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CLARK, ORLO, M.D. Department of Surgery
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Our research continues to focus on the mechanisms involved in the initiation, development, growth, invasion and distant spread of thyroid cancer. Perhaps equally important are our investigations regarding methods to inhibit tumor growth, invasion and metastasis by inducing tumor re-differentiation, increasing apoptosis, as well as decreasing tumor proliferation. These investigations have involved the use of retinoic acid, PPAR g agonists, histone deacetylase inhibitors, and other agents to redifferentiate the thyroid cancers, and to make them more responsive to treatment with 131–I ablation therapy and perhaps also to thyroid hormone suppressive therapy.
We are now using combinations of these agents both to see if various combinations of medications will be more effective than single agents and determine what mechanisms involved in tumor growth and metastasis. We have also used these agents in combination with chemotherapy and heat shock protein inhibitors.
We have recently completed a prospective clinical investigation regarding the use of retinoic acid in patients with thyroid cancer and have initiated a prospective investigation regarding the use of rosiglitazone in a similar group of thyroid cancer patients that are thyroglobulin (Tg) positive and Tg negative.Other investigations include basic science and clinical studies in patients with primary hyperparathyroidism and adrenal tumors. Our parathyroid studies include evaluation of the changing surgical approaches used to treat patients with hyperparathyroidism and the development of new techniques to localize parathyroid tumors.
Selected References
Park J-W et al: The Heat Shock Protein 90-Binding Geldaamycin Inhibits Cancer Cell Proliferation, Down-Regulates Oncoproteins, and Inhibits Epidermal Growth Factor-Induced Invasion in Thyroid Cancer Cell Lines. J Clin Endocrinol Metab 88: 3346-3353, 2003.
Park JW et al: Modulation of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand-Induced Apoptosis by Chemotherapy in Thyroid Cancer Cell Lines. Thyroid 13: 1103-1110, 2003.
Park JW et al: Redifferentiation therapy for thyroid cancer. Surg Clin North Am 84: 921-43, 2004.
Park JW et al: Troglitazone, the Peroxisome Proliferator-Activated Receptor (PPAR) Gamma Agonist Inhibits Growth and Down Regulates Differentiation Marker CD-97 in Thyroid Cancer Cell Lines. Thyroid 15: 232-31, 2005.