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Background: Epidemiology studies have shown an inconclusive relationship between phytoestrogen intake and ovarian cancer risk and there have been no relevant meta-analyses directly regarding this topic. The purpose of the present meta-analysis was therefore to investigate any association between phytoestrogen intake and ovarian cancer in detail. Materials and Methods: We conducted a search of PubMed, EMBASE, EBSCO, the Cochrane Library, CNKI and Chinese Biomedical Database (up to April 2014) using common keywords for studies that focused on phytoestrogen and ovarian cancer risk. Study-specific risk estimates (RRs) were pooled using fixed effect or random-effect models. Results: Ten epidemiologic studies were finally included in the meta-analysis. The total results indicated higher phytoestrogen intake was associated with a reduced ovarian cancer risk (RR, 0.70; 95%CI: 0.56-0.87). The association was similar in sensitivity analysis. Meta regression analysis demonstrated sources and possibly types and regions as heterogeneous factors. Subgroup analysis of types, sources and regions showed that isoflavones (RR: 0.63; 95%CI: 0.46, 0.86), soy foods (RR: 0.51; 95%CI: 0.39, 0.68) and an Asian diet (RR: 0.48; 95%CI: 0.37, 0.63) intake could reduce the incidence of ovarian cancer. Conclusions: Our findings show possible protection by phytoestrogens against ovarian cancer. We emphasize specific phytoestrogens from soy foods, but not all could reduce the risk. The habit of plentiful phytoestrogen intake by Asians is worthy to recommendation. However, we still need additional larger well designed observational studies to fully characterize underlying associations.

The present study aimed to investigate whether gonadotropin-releasing hormone analogues (GnRH-as), including GnRH agonists and antagonists, affect endometrial homeobox (Hox) a10 DNA methylation during the implantation window in mice. GnRH analogue mouse models were used and were treated with either human menopausal gonadotropin (HMG) and a GnRH agonist or HMG and a GnRH antagonist. Uterus samples were collected 48 h after GnRH analogue treatment or ovulation. Bisulfite sequencing polymerase chain reaction (PCR), quantitative-PCR and western blot analysis were performed to assess Hoxa10 and integrin β3 expression. Scanning electron microscope analyses were conducted to analyze pinopode development. Compared with the natural cycle control mice, mice in the GnRH analogue groups were found to exhibit increased levels of methylation at the Hoxa10 promoter, decreased Hoxa10 mRNA and protein expression and disrupted pinopode development. These findings suggest that GnRH-as may be associated with altered Hoxa10 DNA methylation, thus GnRH-as may affect uterine Hoxa10 expression and endometrial receptivity.

Polychlorinated biphenyls (PCBs) are one of the most common endocrine-disrupting chemicals and have obvious toxicity on human reproductive development. The aim of our study was to investigate the toxicity of chronic 2,3',4,4',5-pentachlorobiphenyl (PCB 118) exposure on embryo implantation and endometrial receptivity, with the possible mechanism of DNA methylation involved. Virgin CD-1 female mice (3 weeks old) were housed and orally treated with PCB 118 (0, 1, 10, 100 μg/kg) for a month. After mating with fertile males, the pregnant mice were killed on gestation day 4.5. Compared with the control group, implantation failures were observed in 1 μg/kg PCB 118- and 100 μg/kg PCB 118-treated groups. Abnormal endometrial morphology with open uterine lumens and densely compact stromal cells and poorly developed pinopodes were substantially in response to PCB 118 doses above, as well as the significant downregulation of implantation-associated genes (estrogen receptor 1, homeobox A10 [HOXA10], integrin subunit beta 3) and hypermethylation in the promoter region of HOXA10 further. It was confirmed that chronic exposure to PCB 118 produced an increased number of implantation failures in association with a defective uterine morphology during the implantation period. Alterations in methylation of HOXA10 could explain, at least in part, the mechanism of effects of PCB 118 exposure on the implantation process.

Bevacizumab (Bev) combined with chemotherapy significantly improves progression-free survival (PFS) but not overall survival (OS) in patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). The efficacy and safety depend on the type of chemotherapy combined with Bev. We performed a meta-analysis of phase III trials to evaluate the efficacy and safety of Bev + standard chemotherapy for HER2-negative MBC. The Cochrane Central Register of Controlled Trials, the Cochrane databases, EMBASE, MEDLINE, and ClinicalTrials.gov were analyzed. The primary outcomes included PFS, OS, and toxicity. Event-based hazard ratios (HRs) and relative risks (RRs) were expressed with the 95% confidence intervals (CIs). Four randomized controlled trials consisting of 3082 patients were included. Bev + standard chemotherapy improved PFS (HR 0.70, CI 0.64-0.77, P = 0.000) but had no effect on OS (HR 0.92, CI 0.82-1.02, P = 0.119). Bev + chemotherapy increased the incidence of febrile neutropenia (RR 1.45, CI 1.00 to 2.09, P = 0.048), proteinuria (RR 11.68, CI 3.72-36.70, P = 0.000), sensory neuropathy (RR 1.33, CI 1.05-1.70, P = 0.020), and grade ≥3 hypertension (RR 13.94, CI 7.06-27.55, P = 0.000). No differences in efficacy were observed between Bev + paclitaxel and Bev + capecitabine (Cape), but Bev + Cape increased the incidence of neutropenia. Bev + standard chemotherapy improved PFS in HER2-negative MBC patients. No benefit in OS was observed. Bev + Cape and Bev + paclitaxel had similar treatment efficacy, but Bev + Cape had a higher incidence of neutropenia.