E2Fs are a family of pivotal transcription factors. Accumulative evidence indicates that aberrant expression or activation of E2Fs is a common phenomenon in malignances, and significant associations have been noted between E2Fs and tumorigenesis or progression in a wide range of cancers. However, the expression patterns and exact roles of each E2F contributing to tumorigenesis and progression of ovarian cancer (OC) have not yet been elucidated. In this study, we investigated the distinct expression and prognostic value of E2Fs in patients with OC by analyzing a series of databases, including ONCOMINE, GEPIA, cBioPortal, Metascape, and Kaplan–Meier plotter. The mRNA expression levels of E2F1/3/5/8 were found to be significantly upregulated in patients with OC and were obviously associated with tumor stage for OC. Aberrant expression of E2F2/5/7/8 was found to be associated with the clinical outcomes of patients with OC. These results suggest that E2F2/5/8 might serve as potential prognostic biomarkers and targets for OC. However, future studies are required to validate our findings and promote the clinical utility of E2Fs in OC.

BackgroundQuantitative analyses of circulating cell-free DNA (cfDNA) are potential methods for the detection of ovarian cancer. Many studies have evaluated these approaches, but the results were too inconsistent to be conclusive. This study is the first to systematically evaluate the accuracy of circulating cfDNA for the diagnosis of ovarian cancer by conducting meta-analysis.MethodsWe searched PubMed, Embase, Cochrane Library and the Chinese National Knowledge Infrastructure (CNKI) databases systematically for relevant literatures up to December 10, 2015. All analyses were conducted using Meta-DiSc1.4 and Stata 12.0 software. Sensitivity, specificity and other measures of accuracy of circulating cfDNA for the diagnosis of ovarian cancer were pooled. Meta-regression was performed to identify the sources of heterogeneity.ResultsThis meta-analysis included a total of 9 studies, including 462 ovarian cancer patients and 407 controls. The summary estimates for quantitative analysis of circulating cfDNA in ovarian cancer screen were as follows: sensitivity, 0.70 (95% confidence interval (CI), 0.65–0.74); specificity, 0.90 (95% CI, 0.87–0.93); positive likelihood ratio, 6.60 (95% CI, 3.90–11.17); negative likelihood ratio, 0.34 (95% CI, 0.25–0.47); diagnostic odds ratio, 26.05 (95% CI, 14.67–46.26); and area under the curve, 0.89 (95% CI, 0.83–0.95), respectively. There was no statistical significance for the evaluation of publication bias.ConclusionsCurrent evidence suggests that quantitative analysis of cfDNA has unsatisfactory sensitivity but acceptable specificity for the diagnosis of ovarian cancer. Further large-scale prospective studies are required to validate the potential applicability of using circulating cfDNA alone or in combination with conventional markers as diagnostic biomarker for ovarian cancer and explore potential factors that may influence the accuracy of ovarian cancer diagnosis.

Increasing evidence indicates that elevated neutrophil to lymphocyte ratio (NLR) are related with poor prognosis in various types of tumors. However, the prognostic role of NLR in patients with ovarian cancer (OC) remains controversial. Thus, the current meta-analysis aimed to investigate the prognostic role of NLR in patients with OC. A total of 16 studies with 4,910 patients were included. By pooling hazard ratios (HRs) with 95% confidence intervals (CIs) and odds ratios (ORs) with 95% CIs from each study. The results demonstrated that elevated pretreatment NLR was significantly related to poor OS (HR: 1.50, 95% CI: 1.27-1.77) and PFS (HR: 1.53, 95% CI: 1.28-1.84) in patients with OC. Subgroup analyses was divided by ethnicity, sample size, histologic types, cut-off value of NLR, analysis method and NOS score, but the results did not showed any significant change the main results. This meta-analysis revealed that elevated pretreatment NLR might be a predicative factor of poor prognosis in OC patients.

BackgroundIncreased aberrant expression or activation of the epidermal growth factor receptor (EGFR) family members has been reported in a wide range of cancers, and the EGFR family of tyrosine kinases has emerged as an important therapeutic target in malignancies. However, the expression patterns and exact roles of each distinct EGFR family member, which contribute to tumorigenesis and progression of ovarian cancer (OC), are yet to be elucidated.Materials and methodsIn the current study, we report the distinct expression and prognostic value of EGFR family members in patients with OC by analyzing a series of databases including ONCOMINE, Gene Expression Profiling Interactive Analysis, Kaplan–Meier plotter, cBioPortal, and Database for Annotation, Visualization and Integrated Discovery .ResultsIt was found that in patients with OC, mRNA expression levels of ERBB2/3/4 were significantly upregulated, whereas the transcription levels of EGFR were downregulated. Aberrant EGFR expression and ERBB2/3/4 mRNA levels were associated with OC prognosis.ConclusionThese results suggest that EGFR and ERBB3/4 are distinct prognostic biomarkers and may be potential targets for OC. These results may be beneficial to better understand the molecular underpinning of OC and may be useful to develop tools for more accurate OC prognosis and for promoting the development of EGFR-targeted inhibitors for OC treatment.

Circulating miRNAs, especially the combination of multiple circulating miRNAs, are promising biomarkers for the diagnosis of ovarian cancer. However, further large-scale prospective studies are necessary to validate the applicability of the miRNAs in the early detection of ovarian cancer.

We report here on a novel procedure for measuring glycogenolysis in rat adipocytes. In this procedure, cells are incubated for 30 min at 37 degrees C with insulin or vanadate, and with [U-14C]glucose to label the glycogen pool with radioactive glucose. The cells are washed and preincubated for an additional 1 h, before being assayed. The extent of glycogenolysis is determined by the decrease in radioactivity in precipitated glycogen, which was quite substantial under experimental conditions facilitating glycogenolysis. From the assay, we determined the following. (a) Glycogenolysis is activated in rat adipocytes in response to lipolytic hormones (i.e. catecholamines and adrenocorticotropic hormone). (b) Other agents and conditions elevating intracellular adenosine 3',5'-monophosphate levels (i.e. cholera toxin, dibutyryladenosine 3',5'-monophosphate, and isobutylmethylxanthine) also activate glycogenolysis. (c) Glycogenolysis (as opposed to lipolysis) is activated at concentrations of adrenocorticotropic hormone or isoproterenol 7-11-fold lower and at adenosine 3',5'-monophosphate concentrations 7-fold lower. (d) Calyculin A, a specific inhibitor of protein phosphatase 1, activates glycogenolysis as well. Calyculin A also activates lipolysis at an equimolar potency. (e) Insulin does not antagonize glycogenolysis in rat adipocytes. In conclusion, the assay allowed us to compare glycogenolysis to lipolysis within the same cell, and to find that the sensitivity to hormones and adenosine 3',5'-monophosphate was about 1 order of magnitude higher for glycogenolysis than for lipolysis. A more striking finding was the inability of insulin to antagonize glycogenolysis in the rat adipose cell, an effect which occurs readily in liver and muscle cells via protein phosphatase 1-activating machinery. This rules out a role for adipose protein phosphatase 1 activation in the mechanism by which insulin antagonizes lipolysis and supports the contention that the insulin effect in lowering adenosine 3',5'-monophosphate levels is the central mechanism by which insulin antagonizes lipolysis.

This study was to investigate the effect of annexin A5 on testosterone secretion from primary rat Leydig cells and the underlying mechanisms. Isolated rat Leydig cells were treated with annexin A5. Testosterone production was detected by chemiluminescence assay. The protein and mRNA of Steroidogenic acute regulatory (StAR), P450scc, 3β-hydroxysteroid dehydrogenase (3β-HSD), 17β-hydroxysteroid dehydrogenase (17β-HSD), and 17α-hydroxylase were examined by Western blotting and semi-quantitative RT-PCR, respectively. Annexin A5 significantly stimulated testosterone secretion from rat Leydig cells in dose- and time-dependent manners and increased mRNA and protein expression of StAR, P450scc, 3β-HSD, and 17β-HSD but not 17α-hydroxylase. Annexin A5 knockdown by siRNA significantly decreased the level of testosterone and protein expression of P450scc, 3β-HSD, and 17β-HSD. The significant activation of ERK1/2 signaling was observed at 5, 10, and 30 min after annexin A5 treatment. After the pretreatment of Leydig cells with ERK inhibitor PD98059 (50 μmol l−1) for 20 min, the effects of annexin A5 on promoting testosterone secretion and increasing the expression of P450scc, 3β-HSD, and 17β-HSD were completely abrogated (P < 0.05). Thus, ERK1/2 signaling is involved in the roles of annexin A5 in mediating testosterone production and the expression of P450scc, 3β-HSD, and 17β-HSD in Leydig cells.

PubMed, and also report some research progress of acrosome formation in our laboratory. Results: Acrosome formation can be divided into four stages: Golgi-phase, cap-phase, acrosome-phase and maturation-phase. In the past 10 years, with gene targeting technology, more than ten genes were identified to be related acrosome formation in mice. Those genes include Casein kinase II α´ catalytic subunit (Csnk2a2), HIV-1 Revbinding protein (Hrb), Golgi-associated PDZ-and coiledcoil motif-containing protein (Gopc), Beta-glucosidase 2 (Gba2), Zona pellucida binding protein 1 (Zpbp1), protein interacting with C kinase 1 (Pick1), heat shock protein 90kDa beta member 1 (Hsp90β1), autophagy-related gene 7 (Atg7), sperm acrosome associated 1 (Spaca1), Dpy-19-like protein 2 (Dpy19l2) and stromal membraneassociated protein 2 (Smap2). Recently, we generated a Ccdc62 knockout mouse model with CRISPR-Cas9 system. A preliminary data showed that the male mice with Ccdc62 knockout were infertile, and 98% of sperm showed abnormal head with very lower motility, which suggested that Ccdc62 played a very important role in mouse acrosome formation. Globozoospermia is a rare type of teratozoospermia accounting for <0.1% of male infertility. It has reported that the mutation of SPATA16, PICK1 and DPY19L2 were related to clinical globozoospermia. Conclusions: The process of acrosome formation is regulated by multiple genes and its disorder will results in globozoospermia.