Calcium and calcium channels are closely related to the estrogen-induced nongenomic effect of endometrial carcinoma, but the specific role of calcium channels is unknown. This study aimed to explore the expression and the biologic effect of the L-type calcium channel in endometrial carcinoma cells and to clarify the molecular mechanism of the relationship between L-type calcium channels and estrogen. The immunohistochemical results showed that Ca(2+) channel subunit α 1D (Cav1.3) expression was high in atypical hyperplasia (1.90 ± 0.35) and endometrial carcinoma tissues (2.05 ± 0.82) but weak (0.80 ± 0.15) in benign endometrial tissues (P < 0.05). Treatment with 17β-estradiol rapidly increased Cav1.3 expression in a dose- and time-dependent manner, and 100 nM cell-impermeable β-estradiol-6-(O-carboxymethyl)oxime:bovine serum albumin also promoted Cav1.3 expression. Transfection with small interfering RNA against G protein-coupled estrogen receptor (GPER) suppressed estrogen-induced up-regulation of Cav1.3 compared with control cells and markedly reduced the estrogen-induced phosphorylation of ERK1/2 and CREB. Knocking down the Cav1.3 significantly suppressed estrogen-stimulated Ca(2+) influx, cell proliferation, and migration in endometrial cancer cells. Taken together, Cav1.3 was overexpressed in atypical hyperplasia and endometrial carcinoma, and the estrogen-induced phosphorylation of downstream molecular ERK1/2 and CREB is the result of activation of the GPER pathway. L-type channel Cav1.3 is required for estrogen-stimulated Ca(2+) influx and contributes broadly to the development of endometrial cancer. The Cav1.3 channel may be a new target for endometrial carcinoma treatment.
The aim was to evaluate the efficacy and safety of different combination strategies for prophylaxis of venous thromboembolism (VTE) after gynecologic surgery in patients at different levels of risk. This was a prospective multicenter randomized controlled study, in which 625 women who would undergo pelvic surgery for gynecologic diseases were stratified into three risk groups and then randomized into four groups to receive graduated compression stockings (GCS) alone (group A), GCS + low molecular weight heparin (LMWH) (group B), GCS + intermittent pneumatic compression (IPC) (group C), and GCS + IPC + LMWH (group C), respectively. The overall incidence of DVT was 5.1%. Group A had the highest incidence of DVT (8.8%), followed by group C (5.2%), group B (3.8%), and group D (2.6%). There was a significant difference in the incidence of DVT between groups A and D. The incidence of DVT was significantly lower in LMWH-treated patients (group B + group D) than in non-LMWH-treated patients (group A + group C). In conclusion, combination prophylaxis, especially LMWH-containing strategies, is better than monoprophylaxis in reducing VTE after gynecologic surgery. Risk-stratified prophylactic strategies should be implemented in patients undergoing gynecologic surgery, with LMWH-containing strategies being recommended for high-risk and very-high-risk patients.
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