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Title of Research Project: Botanical drug program: Molecular basis for regulation of estrogen-dependent breast cancer cell proliferation by Epimedium prenylflavonoids Name of Supervisors: Professor E. L. Yong (Head, Dept of Obstetrics & Gynaecology ), Asst Professor Lawrence Lee, MD, PhD (Johns Hopkins). Contact Details: [email protected] Short Description Epimedium spp (Berberidacea,) is one of the most popular “yang” tonic herbs in Traditional Chinese Medicines. It has been described in ancient medicine literatures like Shen Nong Ben Cao Jing and Ben Cao Gang Mu to “reinforce the kidney yang, strengthen tendons and bones, and relieve rheumatic conditions” and indicated “for impotence, seminal emission, weakness of the limbs, rheumatoid arthralgia with numbness and muscle contracture, and climacteric hypertension” Our most recent in vitro studies showed that Epimedium extracts exert estrogenic activity and yet it modulates the MCF-7 breast cancer proliferation in the presence of physiological level of estradiol compared to the presence of estradiol alone. As such, co-administration of both Epimedium flavonoid with estradiol might be effective to reduce the increased breast cancer cases among patients undergoing hormone replacement therapy. The aim of this study is to understand the molecular mechanism of modulation of breast cancer proliferation in the presence of both estradiol and Epimedium flavonoid. This will be followed by in vivo study on nude mice. This study in collaboration with Dr. Willmar Schwabe GmbH & Co. KG, Germany is supervised by a renowned and very well published investigator: NUH clinician-scientist (Prof. Yong). This program allows the student to enjoy the full process of a unique botanical drug development, including molecular mechanisms, pharmacokinetic/pharmacodynamic modeling, animal models for efficacy and toxicology, drug registration in Singapore (estimated in Feb. 2009), leading to human clinical trials. Systematic training will be provided from experienced lab technicians/senior research fellows and to master the core techniques including recombinant protein expression on mammalian system and gene transcription regulation by realtime RT-PCR, GC-MS, LC-MS, animal and human PK/PD training which are required for the study. References on this project can be acquired by sending email request to: Dr. Shen Ping ([email protected]). Further details see: http://www.nus.edu.sg/ngs/supervisors_cv/yong_eu_leong.pdf Recent Relevant Publications: 1. P. Shen, S.P. Wong, J. Li, E.L. Yong, J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 877 (2009) 71-78. 2. Shih Peng Wong, Shih Peng Wong; Ping Shen; L. Lee; J. Li; E.L. Yong, Journal of Pharmaceutical and Biomedical. (2009), in review. 3. E.L. Yong, S.P. Wong, P. Shen, Y.H. Gong, J. Li, Y. Hong, Novartis Found. Symp. 282 (2007) 173-178. 1. P. Shen, B.L. Guo, Y. Gong, D.Y. Hong, Y. Hong, E.L. Yong, Phytochemistry 68 (2007) 14481458. 2. Y. Gong, S.C. Yip, S.K. Thamarai, J. Zhang, H.K. Lee, E.L. Yong, J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 860 (2007) 166-172. 3. S.P. Wong, J. Li, P. Shen, Y. Gong, S.P. Yap, E.L. Yong, Assay Drug Dev. Technol. 5 (2007) 355-362. 4. S.P. Yap, P. Shen, J. Li, L.S. Lee, E.L. Yong, J. Ethnopharm. 113 (2007) 218-224. 5. S.P. Yap, P. Shen, M.S. Butler, Y. Gong, C.J. Loy, E.L. Yong, Planta Med. 71 (2005) 114-119.