Raj Tiwari PhD, Jan Geleibter Phd, Stim Schantz MD, Edward Shin, MD
Two hundred million people worldwide are affected by thyroid proliferating diseases (TPD) including goiter. Women are three times more susceptible than men and overall the incidence of thyroid dysfunction occurring in one in eight women is a sizable health issue and compares to breast cancer risk. The focus of our research is to define the regulatory link of the estrogen mediated cellular and growth regulating signal transduction aberration in TPD using cell culture, animal model and human clinical specimen and explore relevant intervention strategies.
We and others have observed that thyroid cells (transformed and non-transformed) are estradiol (E2)-responsive; can metabolize estradiol; express the estrogen receptor (ER); estrogen mobilizes Bone Marrow-Endothelial Cells to induce neovascularization in response to injury. Intervention studies in the laboratory and clinical trials initiated by us suggest that the diet derived bioactive food component the antiestrogen, DIM down regulates the Akt pathway and modulated estrogen metabolism in cells; a fourteen day supplementation (150 X4 mg) in patients results in detectable levels in biological fluids (blood and urine) and thyroid tissues. Coupled with these observations in our laboratory and the report that DIM inhibits angiogenesis, we are testing the following hypothesis “inhibitors of estrogen mediated angiogenesis by BM-EC and Akt-estrogen crosstalk signaling pathway in goiter are clinically utilizable intervention points for TPD management”. Thus, we are currently:
In the next three years we will focus our attention on two aspects of our program:
Future studies and the subject of grant proposals will be designing small molecular weight inhibitors of the estrogen-activated pathways for the management of TPD.
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