trelstar has been researched along with afimoxifene* in 2 studies
2 other study(ies) available for trelstar and afimoxifene
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Analogs of GnRH-I and GnRH-II inhibit epidermal growth factor-induced signal transduction and resensitize resistant human breast cancer cells to 4OH-tamoxifen.
About 50-64% of human breast cancers express receptors for GnRH-I. Direct antiproliferative effects of analogs of GnRH-I on human breast cancer cell lines have been shown. They are at least in part mediated by antagonizing growth promoting effects of estradiol, epidermal growth factor (EGF) or insulin-like growth factor. Recently, expression of a putative receptor for GnRH-II in human tissues was demonstrated. Antiproliferative effects of GnRH-II in human endometrial and ovarian cancer cells were shown not to be mediated through the GnRH-I receptor. Now we demonstrate direct anti-proliferative effects of the GnRH-I analog Triptorelin and the GnRH-II analog [d-Lys(6)]GnRH-II in MCF-7 and T47D human breast cancer cells expressing GnRH-I receptors and putative GnRH-II receptors. Pretreatment with Triptorelin or [d-Lys(6)]GnRH-II blocked EGF-induced autophosphoryla-tion of EGF receptor and activation of mitogen-activated protein kinase (extracellular-signal-regulated kinase 1/2 (ERK1/2)) in these cells. In sublines of MCF-7 and T47D cells, which were developed to be resistant to 4OH-tamoxifen, HER-2/p185 was overexpressed. Pretreatment of these cell lines with Triptorelin or [d-Lys(6)]GnRH-II completely abolished resistance to 4OH-tamoxifen, assessed by 4OH-tamoxifen-induced apoptosis. Analogs of GnRH-I and GnRH-II counteract EGF-dependent signal transduction in human breast cancer cells with expression of receptors for GnRH-I and GnRH-II. Through this mechanism, they probably reverse acquired resistance to 4OH-tamoxifen mediated through overexpression or activation of receptors of the c-erbB family. Topics: Antineoplastic Agents; Apoptosis; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Drug Resistance, Neoplasm; Enzyme Activation; Epidermal Growth Factor; ErbB Receptors; Estrogen Antagonists; Extracellular Signal-Regulated MAP Kinases; Female; Gefitinib; Gonadotropin-Releasing Hormone; Humans; Phosphorylation; Quinazolines; Signal Transduction; Tamoxifen; Triptorelin Pamoate | 2005 |
Compared effects of GnRH analogs and 4-hydroxytamoxifen on growth and steroid receptors in antiestrogen sensitive and resistant MCF-7 breast cancer cell sublines.
Antiestrogens, such as tamoxifen, have a direct antitumor action and are widely used in cancer therapy. The direct antitumor action of GnRH analogs has been documented in both in vitro and clinical studies. GnRH analog direct action could therefore provide an alternative approach in postmenopausal patients developing antiestrogen resistance, a frequent cause of relapse during hormonal treatment of breast cancer. This study was carried out to compare the effects of two GnRH analogs (the agonist Decapeptyl and the antagonist BIM 21009C) and the antiestrogen 4-hydroxy-tamoxifen (OH-TAM) on proliferation in antiestrogen-responsive or antiestrogen-resistant human breast cancer cell lines (MCF-7, MCF-7 LY2). Ineffective when used without estrogen stimulation, both of the GnRH analogs and OH-TAM inhibit the 17 beta-estradiol-stimulated growth of the estrogen-responsive cell line MCF-7. Compared with parental MCF-7 cell line responsiveness, the antiestrogen-resistant variant MCF-7 LY2 appears to be resistant to GnRH analogs. These findings indicate similarities between the two types of compounds with regard to their antiestrogenic effects on growth observed in vitro. However, since unlike OH-TAM, Decapeptyl displays no effect on steroid receptor levels of sensitive MCF-7 cells, the intracellular inhibitory mechanisms of these drugs are probably in part different. This study suggests that the direct effect of the studied GnRH analogs would not be a potent tool for treating antiestrogen-resistant breast tumors. Topics: Antineoplastic Agents; Breast Neoplasms; Cell Division; Drug Screening Assays, Antitumor; Estradiol; Estrogen Antagonists; Estrogens; Gonadotropin-Releasing Hormone; Humans; Receptors, Steroid; Stimulation, Chemical; Tamoxifen; Triptorelin Pamoate; Tumor Cells, Cultured | 1990 |