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Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endometrial cancer develops during exposure to estrogen unopposed by progesterone. Traditional formulations for menopausal hormone therapy include a progestin in women with a uterus. However, progestin exposure increases breast cancer risk in postmenopausal women. Alternatives to progestin include bazedoxifene (BZA), a selective estrogen receptor modulator, which prevents estrogen induced endometrial hyperplasia in clinical trials. Molecular mechanisms responsible for BZA's antiproliferative effect are not fully elucidated. We profiled endometrial adenocarcinoma, hyperplasia, and normal proliferative endometrium for differential expression in genes known to be regulated by estrogens or progesterone. Fibroblast growth factor (FGF)18, a paracrine growth factor promoting epithelial proliferation, was significantly increased in adenocarcinoma. Progesterone represses FGF18 by inducing heart and neural crest derivatives expressed transcript 2 (HAND2) in stromal cells. Notably, we confirmed lower HAND2 mRNA in adenocarcinoma, along with higher FGF tyrosine kinase receptor 2 and E74-like factor 5, collectively promoting FGF18 activity. We hypothesized BZA reduces epithelial proliferation by inhibiting FGF18 synthesis in stromal cells. To determine whether BZA regulates FGF18, we treated primary stromal cells with BZA or vehicle. In vitro, BZA reduced FGF18, but did not affect, HAND2. CD1 female mice received either BZA, conjugated estrogen (CE), or combined BZA/CE for 8 weeks. CE-treated mice had nearly 3-fold higher FGF18 expression. In contrast, BZA-treated mice, alone or with CE, had similar FGF18 as controls. Unexpectedly, BZA, alone or with CE, reduced HAND2 more than 80%, differing from progesterone regulation. Reduction of FGF18 is a potential mechanism by which BZA reduces endometrial proliferation and hyperplasia induced by estrogens. However, BZA works independently of HAND2, revealing a novel mechanism for progestin-free hormone therapy in postmenopausal women.
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PMID:Endometrial Cancer-Associated FGF18 Expression Is Reduced by Bazedoxifene in Human Endometrial Stromal Cells In Vitro and in Murine Endometrium. 2726 14

Expression of E74-like factor 5 (ELF5) in endometrial carcinoma tissues and its clinical significance were investigated. Eighty-four endometrial carcinoma tissues, 30 cases of atypical hyperplasia of endometrium and 30 cases of normal endometrial tissues were selected. Immunohistochemical method was utilized to detect the expression of ELF5 in different endometrial tissues. Moreover, its correlation with clinical pathological indexes of patients with endometrial carcinoma was analyzed. The postoperative follow-up was conducted in all the patients with endometrial carcinoma until June 30th, 2017. The Kaplan-Meier method was used for survival analysis so as to analyze the association of ELF5 expression level with clinical pathological indexes; Cox's proportional hazards regression model was utilized for univariate and multivariate analyses to screen independent risk factors for prognosis of endometrial carcinoma. In normal endometrial tissues, atypical hyperplasia and endometrial carcinoma tissues, the positive expression rates of ELF5 showed a decreased tendency (P=0.016). The positive expression rate of ELF5 in endometrial carcinoma tissues was lower in comparison to normal endometrial tissues (P=0.016). The expression of ELF5 was in accordance with the International Federation of Gynecology and Obstetrics (FIGO) staging of endometrial carcinoma (P<0.05), pathological grading (P<0.05), pathological typing (P=0.001), state of lymph node metastasis (P<0.05) and depth of myometrial invasion (P<0.05). Kaplan-Meier method for survival analysis showed that the average survival time of patients with negative ELF5 expression was shorter in comparison to the patients with positive expression (P=0.004). FIGO staging (P=0.004), pathological grading (P=0.048), depth of myometrial invasion (P=0.024) and lymph node metastasis (P=0.020) were related to the prognosis of patients with endometrial carcinoma, The univariate Cox's regression model analysis indicated that FIGO staging (P=0.010), pathological grading (P=0.040), depth of myometrial invasion (P=0.037), lymph node metastasis (P=0.029) and ELF5 (P=0.010) were associated with the prognosis of patients with endometrial carcinoma. Further, multivariate analysis revealed that ELF5 was an independent risk factor for prognosis of patients with endometrial carcinoma (P=0.035). The expression of ELF5 has a correlation with the occurrence, development and prognosis of endometrial carcinoma.
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PMID:Expression of ELF5 in endometrial carcinoma tissues and its clinical significance. 3012 51