The long-term goal is to investigate and determine specific factors that lead to development of endometrial cancer in postmenopausal women. Previous work supports the hypothesis that hyperinsulinemia plays a role in the development of endometrial cancer, and that the increased incidence of endometrial cancer seen in obese postmenopausal women may not only be due to increased estrogen production in the adipose tissue, but also due to the increase in the insulin levels.
Specific aims of this continuing research project will be: (1) to fully characterize the nature of insulin resistance in women with endometrial cancer; (2) to perform studies on the ovarian stroma of postmenopausal women with endometrial cancer so as to investigate the mechanism by which insulin stimulates ovarian steroidogenesis; (3) to investigate the possible role of insulin on the development and progression of endometrial cancer; and (4) to investigate the role of insulin-like growth factors (IGF-I, IGF-II) in the development of endometrial cancer.These studies will provide important insight into pathogenesis of endometrial cancer and will aid in the development of preventive measures and new therapeutic approaches to improve cure rates of this cancer.

National Institute of Health (NIH)
National Cancer Institute (NCI)
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Reproductive Biology Study Section (REB)
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University of Texas Medical Br Galveston
Obstetrics & Gynecology
Schools of Medicine
United States
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Sepilian, Vicken; Nagamani, Manubai (2005) Effects of rosiglitazone in obese women with polycystic ovary syndrome and severe insulin resistance. J Clin Endocrinol Metab 90:60-5
Nagamani, Manubai; Urban, Randall J (2003) Expression of messenger ribonucleic acid encoding steroidogenic enzymes in postmenopausal ovaries. J Soc Gynecol Investig 10:37-40
Nowicki, S; Nowicki, B; Pham, T et al. (2001) Expression of decay accelerating factor in endometrial adenocarcinoma is inversely related to the stage of tumor. Am J Reprod Immunol 46:144-8
Lu, L J; Anderson, K E; Grady, J J et al. (2001) Effects of an isoflavone-free soy diet on ovarian hormones in premenopausal women. J Clin Endocrinol Metab 86:3045-52
Stuart, C A; Wen, G; Williamson, M E et al. (2001) Altered GLUT1 and GLUT3 gene expression and subcellular redistribution of GLUT4: protein in muscle from patients with acanthosis nigricans and severe insulin resistance. Metabolism 50:771-7
Lu, L J; Anderson, K E; Grady, J J et al. (2000) Decreased ovarian hormones during a soya diet: implications for breast cancer prevention. Cancer Res 60:4112-21
Lu, L J; Cree, M; Josyula, S et al. (2000) Increased urinary excretion of 2-hydroxyestrone but not 16alpha-hydroxyestrone in premenopausal women during a soya diet containing isoflavones. Cancer Res 60:1299-305
Nagamani, M; Urban, R J (1999) Increased expression of messenger ribonucleic acid encoding cytochrome P450 cholesterol side-chain cleavage and P450 17alpha-hydroxylase enzymes in ovarian hyperthecosis. Fertil Steril 71:328-33
Nagamani, M; Osuampke, C; Kelver, M E (1999) Increased bioactive luteinizing hormone levels and bio/immuno ratio in women with hyperthecosis of the ovaries: possible role of hyperinsulinemia. J Clin Endocrinol Metab 84:1685-9
Stuart, C A; Gilkison, C R; Smith, M M et al. (1998) Acanthosis nigricans as a risk factor for non-insulin dependent diabetes mellitus. Clin Pediatr (Phila) 37:73-9

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