Browsing by Author "Kato, S"
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- Item2-methoxiestradiol induces apoptosis in gynecologic cancer cells but not in normal cell lines established from reproductive tissues.(ELSEVIER SCIENCE INC, 2006) Cuello, MA; Kato, S; Sadarangani, A; Espinoza, N; Lange, S; Villalon, M; Owen, G
- ItemBile acids increase response and expression of human myometrial oxytocin receptor(MOSBY, INC, 2003) Germain, AM; Kato, S; Carvajal, JA; Valenzuela, GJ; Valdes, GL; Glasinovic, JCOBJECTIVE: We tested the hypothesis that during intrahepatic cholestasis of pregnancy bile acids activate the myometrial oxytocin receptor pathway.
- ItemIn vivo and in vitro estrogenic and progestagenic actions of Tibolone(2005) Sadarangani, A; Salgado, AN; Kato, S; Pinto, M; Carvajal, A; Monso, C; Owen, GI; Vigil, PEstrogen and progestin combination in hormone replacement therapy (HRT) increases the incidence of breast cancer, but decreases the endometrial cancer risk of unopposed estrogen. Therefore, a SERM such as Tibolone, that delivers the beneficial, but not the adverse side effects, of steroid hormones would be clinically advantageous. However, data from the Million Women Study suggests that Tibolone increases the risk of both breast and endometrial cancer. Herein, we assessed the estrogenic and progestagenic actions of Tibolone using transvaginal sonography studies and an in vitro model of breast (ZR-75, MCF7) and endometrial cancer (Ishikawa). The known cancer associated proteins (ER, EGFR, STAT5, tissue factor and Bcl-xL) were selected for study. Transvaginal sonography demonstrated that postmenopausal women treated with Tibolone displayed a thinner endometrium than in the late proliferative phase, but had a phenotype characteristic of the secretory phase, thus demonstrating the estrogenic and progestagenic actions of this SERM. In vitro, Tibolone acted as an estrogen in downregulating ER and upregulating Bcl-xL, yet as progesterone, increasing STAT5 and tissue factor in breast cancer cells. The increase in tissue factor by Tibolone correlated with its coagulative potential. Interestingly, EGFR was Lip-regulated by progesterone in the breast and by estrogen in endometrial cells, while Tibolone increased protein levels in both cell types. In conclusion, this study further demonstrates the estrogenic and progestagenic nature of Tibolone. The pattern of regulation of known oncogenes in cells of breast and endometrial origin dictates caution and vigilance in the prescription of Tibolone and subsequent patient monitoring.