Project description:Combination therapy with estrogen and a selective estrogen receptor modulator (SERM) is a promising approach to safely alleviate important side effects related to estrogen deficiency in women at high risk for breast cancer. Data related to endometrial safety of estrogen+SERM co-therapies are limited, however. The primary goal of this study was to evaluate the endometrial profile of low-dose E2 and Tam alone and in combination. In this study 16 postmenopausal female cynomolgus macaques were randomized to receive placebo, low-dose micronized estradiol (E2, 0.25 mg/1800 kcal), the SERM tamoxifen (Tam, 20 mg/1800 kcal), or E2+Tam in a parallel-arm design. Endometrial samples were collected after 4 months of treatment and used for microarray analysis.
Project description:Combination therapy with estrogen and a selective estrogen receptor modulator (SERM) is a promising approach to safely alleviate important side effects related to estrogen deficiency in women at high risk for breast cancer. Data related to endometrial safety of estrogen+SERM co-therapies are limited, however. The primary goal of this study was to evaluate the endometrial profile of low-dose E2 and Tam alone and in combination.
Project description:Preimplantational estrogen exposure to pregnant gilts has been associated with implantation failure, embryonic losses and changes in endometrial mRNA expression. Small non-coding RNAs (ncRNA), especially miRNAs, play a key role in regulation of gene expression. Effects of estrogens on endometrial microRNAs (miRNA), however, have not been investigated in this context so far. Thus, we studied the influence of estradiol-17β (E2) on the endometrial expression profile of miRNAs in the pig at gestational day 10. E2 administered early during pregnancy resulted in significantly higher endometrial estrogen concentrations even at a low dose, but did not disrupt the expression profile of endometrial miRNAs.
Project description:Treatment with the breast cancer drug tamoxifen confers a risk of developing uterine tumors or other endometrial pathologies. Tamoxifen is a selective estrogen receptor modulator, which demonstrates tissue-specific activity although the mechanisms remain poorly understood. Both estradiol and tamoxifen act as estrogen agonists on the human uterus, and therefore have the potential to promote carcinogenicity. Estradiol and tamoxifen elicit cellular responses via the estrogen receptors (ER), which are involved in multiple signalling pathways. The effects at the molecular level are further influenced by the differential recruitment of co-factors and the presence of specific promoter motifs in target genes. In this study, ER positive (+) Ishikawa cells are used as a model to investigate the overall effect of treatment with either 17b-estradiol or 4-hydroxytamoxifen on the gene expression profiles. Keywords: Comparison of estradiol and tamoxifen on Ishikawa human uterine cells after 24h or 48h
Project description:RNA samples from brain, cerebellum, liver, and testis of 3-year-old make Macaca fascicularis was hybridized to the M.fascicularis GeneChip, which was designed by the Laboratory of Genetic Resources, National Institute of Biomedical Innovation. Keywords: Control study
