Estrogen dependent tumors

Alternative mRNA maturation is frequent in tumor tissue expressing ER. In some cases it would give rise to truncated receptors that would maintain the capacity to bind hormones but would have lost their capacity as a transcription factor. Additionally, truncated receptors would be produced that would lack the capacity to bind hormones but would conserve intact their capacity to interact with DNA. In this case, the truncated receptors can become tumorigenic by stimulating the proliferation of cells uncontrolled by hormones. These receptor variants have been the object of exhaustive study at the level of mRNA in tumors of the breast, mainly estrogen-dependent tumors (Clemons et al. 2001 Garcia et al. 1988 Palmieri et al. 2002), but tests for the existence of receptor protein with these characteristics have not corroborated the expectation created by their theoretical interest. 

This drug class has an enormous potential in the primary and secondary prevention of several types of estrogen-dependent tumors, postmenopausal osteoporosis, and cardiovascular and neurodegenerative diseases. 

The main contraindications to oestrogen treatment are estrogen dependent tumors and previous deep vein thrombosis or embolus. 

Estrogens can be associated with endometrial carcinoma, liver tumors, and breast tumors they can also promote the further growth of pre-existing estrogen-dependent tumors. 

Estrogens should be avoided in individuals with current thrombophlebitis or thromboembolism, estrogen-dependent tumors, abnormal genital bleeding without a diagnosis, and pregnancy. They are also contraindicated in apparently healthy women if they have an earlier history of jaundice in pregnancy, hepatic disease, thromboembolism, or porphyria. 

Studies with female CD-I mice with 2% rosemary methanol extract diet increased liver microsomal oxidation and glucuronidation of estradiol and estrone and inhibited uterotropic action (Zhu et al 1998). It is suggested that stimulating certain pathways of estrogen metabolism may be beneficial for the prevention of estrogen-dependent tumors in the target organs of humans and animals. 

Bardin, A., Boulle, N., Lazennec, G., Vignon, F. and Pujol, P. (2004) Loss of ERp expression as a common step in estrogen-dependent tumor progression. Endocrine-Related Cancer, 11, 537-551. 

The issue of using P450 19A1 inhibitors in the treatment of a variety of estrogen-dependent tumors has already been presented. In addition, there is consideration of the use of inhibitors for breast cancer prevention in high-risk individuals . 

Some pyrrolo[l,2-a]imidazoles, described as aromatase inhibitors, are useful in treating gynecomastia and breast cancer or benign prostatic hyperplasia and estrogen-dependent tumors <85EUPI65904, 93MI 802-01>. 

While the inhibition of aromatase activity by PED is well established, some controversy exists as to its inhibition of tumor growth in vivo. Zimniski and coworkers and Puett and coworkers showed that PED was a potent inhibitor of dimethylbenzanthracene-induced mammary tumor growth at a dose of 1 mg/kg/day as well as of human ovarian carcinoma in athymic mice. In contrast, di Salle and coworkers and Zaccheo and coworkers " found that PED did not affect the growth of established tumors in the same model, nor did it prevent the appearance of new neoplasms. Thus, it appears that more in vivo studies on the inhibition of tumor growth are required before firm conclusions can be drawn on its role in estrogen-dependent tumor biology. 

Aromatase - Inhibition of aromatase, the cytochrome P-450 enz3rme that oxidizes testosterone to estradiol, offers a means for the control of estrogen-dependent tumors. A number of mechanism-based inhibitors that may act through heme-alkylation have been described for this enzyme. 

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