Cancerous uterine tissues

More recently, another SERM, known as raloxifene (Evista), was developed. Raloxifene is similar to tamoxifen except that it blocks estrogen receptors on breast and uterine tissues and may therefore produce beneficial effects (inhibiting breast cancer, improving bone and cardiovascular function) without increasing the risk of endometrial cancers.30,51,57 Raloxifene is currently approved for treating osteoporosis, and the use of this drug is associated with increased vertebral bone density and a reduced risk of vertebral fractures.30,77... 

The anti-estrogen, tamoxifen, is the most commonly used hormonal therapy for breast cancer and has demonstrated positive effects on the cardiovascular and skeletal systems of postmenopausal women but is associated with an increased risk of uterine cancer. Tamoxifen is described as a SERM, a selective estrogen receptor modulator with a tissue selective profile that is caused by the different distribution of the a- and /3-subtypes of the estrogen receptor (ERa and ER/3) that activate and inhibit transcription respectively (77). These selective effects have been ascribed to differential interactions with gene promotor elements and coregulatory proteins depending on whether the ERa interacts directly, or in a tethered manner with DNA (78). In uterine tissue, tamoxifen interacts with a specific coactivator, SRCl, that is abundant in uterine tissue. 

B8. Bojar, H., Staib, W., Beck, K., and Pilaski, J., Investigations of the thermostability of steroid hormone receptors in lyophilized calf uterine tissue powder. Cancer (Philadelphia) 46,2770-2774 (1980). 

Scientists at the National Institute of Environmental Health Sciences report that a set of three existing tests, when used in combination, provides a rapid assessment of a chemical s potential to mimic the hormone estrogen. One test determines whether the chemical can bind to an estrogen receptor site the second determines whether it activates estrogen-responsive genes in a cell hne and the third determines whether the chemical causes the proliferation of estrogen-responsive uterine tissue in female mice. Using these tests, results can be obtained in 3-5 weeks at a cost of about 15,000, versus 1-2 million for conventional cancer bioassays. ... 

The estrogen receptor affinity of EM-652, the active drug of EM-800, was first measured in human breast cancer and normal human uterine cytosol (Asselin et al., 1980). As measured by competition studies in human breast cancer tissue, the affinity of EM-652 (Aj = 0.047 0.003 nM, RBA = 291, relative to 17p -estradiol set at 100), studied in the presence of... 

Fujii, T. Naito, H. Kioka, H. Tanioka, Y. Murakami, J. Sanada, M. Tanimoto, H. Nakagawa, H. Tanaka, T. Furui, J. Effect of intravaginal administration of cisplating (CDDP) suppositories to uterine cervical cancer-blood and tissue concentrations and the therapeutic effects. Jpn. J. Cancer Chem. 1995, 22, 99-103. 

Leitao MM, Soslow RA, Nonaka D, et al. Tissue microarray immunohistochemical expression of estrogen, progesterone, and androgen receptors in uterine leiomyomata and leiomyosarcoma. Cancer. 2004 101 1455-1462. 

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