Research Interests:

The research interests of this laboratory are to identify the molecular changes underlying the loss of growth control  that is causally involved in the development and progression of human prostate cancer and benign
prostatic hyperplasia. Normal homeostasis of the prostate gland is maintained by a balance between cell proliferation and apoptosis that is regulated by androgens and growth factors signaling pathways. During
neoplastc growth an inbalance in these signal transduction cascades results in decrease apoptosis and increased cell proliferation. The molecular mechanisms and cellular events functionally involved in the impairement of transforming growth factor -beta signaling pathway and the resulting loss of apoptotic cell death and cell cycle regulation are the focus of our efforts. Successful identification of key apoptosis regulators will lead to: a) novel theraputic targets for the effective treatment of prostate cancer patients and b) reliable molecular markers of tumor progression.
 

Recent publications:

1) Winter, R.M., Kramer, A., Borkowski, A. and Kyprianou, N. Loss of caspase-1 and caspase-3 expression in human prostate cancer. Cancer Res., 61:1227-1232, 2001.

2) Bruckheimer, E.M. and Kyprianou, N. Dihydrotesterone enhances TGF-beta induced apoptosis in hormone-sensitive prostate cancer cells. Endocrinology, 142:2419-2426, 2001.

3) Glassman, D., Chon, J., Borkowski, A., Jacobs, S.C. and Kyprianou, N. Combined effect of terazosin and finasteride on prostate apoptosis, cell proliferation and TGF-beta expression in benign prostatic hyperplasis. The Prostate, 47: 45-51, 2001.

4) Benning, C.M. and Kyprianou, N. Quinazoline-derived alpha1- adrenoceptor antagonists induce prostate cancer cell apoptosis via an alpha-adrenoceptor -independent action. Cancer Res., 62: 1-8, 2002.

Partin, J.V., Anglin, I.E. and Kyprianou, N. Quinazoline-based a1adrenoceptor antagonists induce prostate cancer cell apoptosis via TGF-b signaling and IkBa induction. Br. J. Cancer, 88:1615-1621, 2003.

Zeng, L., Rowland, R., Lele, S. and Kyprianou, N. Apoptosis incidence and expression of p53, TGF-β RII receptor, p27^Kipl and Smad4 in benign, premalignant and malignant human prostate. Human Pathol, 35(3): 290-297, 2004.

Garrison, J.B. and Kyprianou, N. “Novel Targeting of Anoikis for Prostate Cancer Therapy,” Current Cancer Drug Targets; (Apoptosis and Cancer Therapeutics), 4:85-95, 2004.

Winter, R.N., Rhee, J. and Kyprianou, N. Caspase-1 enhances the apoptotic sensitivity of human prostate cancer cells to ionizing irradiation. Anticancer Research, 24:1377-1385, 2004.

Shaw, Y-J., Yang, Y-T., Garrison, J.B., Kyprianou, N. and Chen, C-S. Pharmacological exploitation of the alpha1 adrenoceptor antagonist doxazosin to develop a novel class of apoptosis-targeting antitumor agents that block intracellular Akt activation. J. Med. Chem., 47: 4453-4462, 2004.

Keledjian, K., Garrison, B. J. and Kyprianou, N. Doxazosin inhibits vascular endothelial cell adhesion, migration and invasion. , J. Cell. Biochem., 94:374-288, 2005.