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- W2318055005 abstract "CTRC-AACR San Antonio Breast Cancer Symposium: 2008 AbstractsAbstract #3035 Background: Tibolone (Org OD-14, active substance of Livial®) is a synthetic steroid with a 19-nor-testosterone derivative structure. This compound has weak estrogenic, progestagenic, and androgenic properties and is used to prevent climacteric symptoms and postmenopausal bone loss. Tibolone is extensively metabolized in 3a- and 3s-hydroxy-derivatives and their 4-en isomer. Previous studies in this laboratory demonstrated that tibolone and its metabolites are anti-sulfatase agents in the hormone-dependent breast cancer cells: MCF-7 and T-47D, while the present study explores their effect on estrone-sulfatase activity in normal and cancerous breast tissues. Materials and Methods: : Two regions of the mammary tissue from each post-menopausal patient with breast cancer (n=8) were selected : the tumoral tissue and a distant zone which was considered as normal. Slices of tumoral or normal breast tissues (25-95 mg) were incubated in buffer (20 mM Tris-HCl, pH 7.2) with physiological concentrations of [3H]-estrone sulfate (E1S) (5x10-9M) alone or in the presence of tibolone or its metabolites (5x10-5 or 5x10-7M) during 14h at 37°C. E1S, estrone and estradiol were characterized by thin layer chromatography and quantified using the corresponding standard. Results: In breast cancer tissues the sulfatase activity was twice as high as in normal breast tissue. At concentrations of 5x10-7 and 5x10-5M tibolone inhibits sulfatase activity in breast cancer tissue by 25 and 33% respectively. Using the same concentrations for the 3a-hydroxy these were 32 and 57%, for the 3s-hydroxy 22 and 32%, and for 4-en derivatives 0 and 48% respectively. In the normal tissues the values were: for tibolone, 3 and 20%, for the 3a-hydroxy, 16 and 29 %, for the 3s-hydroxy, 13 and 25%, and for the 4-en derivative 0 and 22% respectively. In these experiments, it was observed that estrone does not convert to estradiol. Conclusion: The present data indicates that the estrone sulfatase activity is higher in breast cancer tissue and that the inhibitory effects of tibolone and its metabolites are significantly higher in this tissue than in the normal breast. It is suggested that the present results can open new possibilities in the knowledge of the mechanism of action of tibolone and its metabolites in normal and cancerous breast.Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3035." @default.
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- W2318055005 date "2009-01-15" @default.
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- W2318055005 title "Comparative effect of tibolone and its metabolites on sulfatase activity in normal and cancerous breast tissues." @default.
- W2318055005 doi "https://doi.org/10.1158/0008-5472.sabcs-3035" @default.
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