Acceptance and Continuation of Contraceptive Methods Immediate Postabortion.

BACKGROUND/AIMS: Providing preabortion contraceptive counseling for the method of contraception may reduce the incidence of repeat abortions. This study aimed to compare the acceptance and continuation rates of intrauterine devices (IUDs), combined oral contraceptives (COCs), and condom use after abortion in women who received preabortion contraceptive counseling. METHODS: Women seeking a first-trimester abortion prospectively received preabortion contraceptive counseling and the choice of method of contraception was based on the counseling and not related to prior methods of birth control. Outcomes included continuation of postabortion contraceptive use and repeat abortions over a 6-month follow-up period. RESULTS: Four hundred and fifty-five women (IUD group: n = 161; COC group: n = 149; condom group: n = 135) completed 6-month follow-up after the abortions. At the sixth month follow-up, patients continued using the IUD, COC, and condoms for contraception were 64.2, 10, and 51.5%, respectively. Higher age, being married, parity ≥1, and previous abortion were factors that were associated with more frequent selection of an IUD, while a higher education level was associated with a more frequent selection of COC and condoms. CONCLUSION: The continued use of COCs after abortion is low even with preabortion contraceptive counseling. The IUD offers reliable birth control with a lower discontinuation rate than COCs or condoms.

LRG1 is an independent prognostic factor for endometrial carcinoma.

Endometrial cancer (EC) is one of the most common female malignancies. The patients with high-risk factors may have poor prognosis. Therefore, there is an urgent need to find a new molecule to more accurately predict survival of patients. Leucine-rich-alpha-2-glycoprotein1 (LRG1), one of leucine-rich repeat family, was closely associated with cancer metastasis and poor prognosis. The biological functions and the expression level of LRG1 remain obscure in EC. In this study, by immunohistochemical analysis of 242 EC patient tissues, we found that LRG1 expression was associated with stage and lymphatic metastasis in both test cohort (133 patients) and validation cohort (109 patients). Furthermore, to investigate the prognostic value of LRG1 in endometrial carcinoma, we analyzed the correlation between variables and overall survival with Cox proportional hazard regression. The result showed that LRG1 was an independent prognostic factor for overall survival of endometrial carcinoma patients. To further evaluate the prognostic efficiency of LRG1 in endometrial carcinoma, we compared the sensitivity and specificity of LRG1 in endometrial carcinoma prognosis by logistic regression. The result showed that LRG1 combining with other clinicopathological risk factors was a stronger prognostic model than clinicopathological risk factors alone or their combination. Thus, LRG1 potentially offered clinical value in directing personal treatment for endometrial carcinoma patients.

Increased mean glucose levels in patients with polycystic ovary syndrome and hyperandrogenemia as determined by continuous glucose monitoring.

OBJECTIVE: Women with polycystic ovary syndrome are at risk of developing type 2 diabetes mellitus. This study aimed to evaluate the influence of hyperandrogenemia on glucose metabolism in polycystic ovarian syndrome patients. DESIGN: Cohort study. SETTING: Reproductive Endocrinology Clinic of the Shanghai Sixth People's Hospital. SAMPLE: Fifty-three patients were recruited from June 2008 to December 2009, including 28 women with hyperandrogenism and 25 without hyperandrogenemia. METHODS: Anthropometric parameters, including weight, height, body mass index and waist-to-hip ratio, as well as sex hormones, were measured. An oral glucose tolerance test, including fasting and two hour glucose and insulin levels, was recorded. Insulin resistance was evaluated by homeostatic model assessment of insulin resistance, and patients underwent continuous glucose monitoring. MAIN OUTCOME MEASURES: Mean blood glucose level, mean amplitude of glycemic excursion, frequency of glycemic excursion and the percentage of time of hypoglycemia and hyperglycemia during a 48 h period. RESULTS: No differences in age, body mass index, waist-to-hip ratio, fasting and two hour glucose and insulin concentrations were observed between the groups. The hyperandrogenism group had higher levels of luteinizing hormone and dehydroepiandrosterone sulfate (p < 0.05). However, continuous glucose monitoring showed that the minimal blood glucose and mean blood glucose were significantly higher in hyperandrogenemia group (p = 0.004). The percentage of time for hypoglycemia (≤70 mg/dL) was higher in the hyperandrogenemia group (p = 0.002). CONCLUSIONS: Polycystic ovarian syndrome patients with hyperandrogenemia had an increased mean glucose value, which may place them at increased risk for developing type 2 diabetes.

[Clinical value of hCG ratio of blood in peritoneal cavity versus venous blood in diagnosis of ectopic pregnancy].

OBJECTIVE: To study the value of hCG ratio of blood in peritoneal cavity versus venous blood (RPhCG/VhCG) in diagnosis of early ectopic pregnancy (EP). METHODS: From Mar. 2009 to Oct. 2012, 268 cases with EP (EP group) and 53 women with intrauterine pregnancy with haemoperitoneum (hIUP) (hIUP group) from International Peace Maternity and Child Health Hospital of Shanghai Jiaotong University School of Medicine, Shanghai 6th People Hospital and Shanghai Jiangwan Hospital were enrolled in this prospective study. The HCG of all subjective were measured in blood in peritonea cavity and venous blood, then calculate the ratio of RPhCG/VhCG. Scatter point analysis and ROC were used to differentiate EP, determine threshold of hIUP and evaluate the sensitivity, specificity and accuracy in diagnosis EP preoperatively. RESULTS: The mean RPhCG/VhCG of EP group was 4.35, which was significantly higher than 0.81 in hIUP group (P < 0.01). Scatter point analysis showed that the threshold value of RPhCG/VhCG between ectopic pregnancy and hIUP was 1.0. The overall sensitivity of RPhCG/VhCG in the diagnosis of EP was 98%, the specificity was 100%, the positive predictive value was 100% and the negtive predictive value was 93%. CONCLUSION: RPhCG/VhCG > 1.0 could be used to diagnose and differentiate EP from hIUP accurately.

A case of a naturally conceived pregnancy associated with multiple ovarian cysts in a patient with severe untreated primary hypothyroidism.

There are few reports of multiple ovarian cysts secondary to hypothyroidism, and multiple ovarian cysts associated with pregnancy most commonly occur in association with assisted reproductive technologies. Herein, we report a case of a naturally conceived pregnancy occurring 2 years after stopping treatment for primary hypothyroidism. The patient developed multiple ovarian cysts in the first trimester, and laboratory studies and ultrasonography were consistent with hypothyroidism. Herein, we present the case and discuss the importance of prenatal screening for hypothyroidism.

[Characteristics of pelvic diaphragm hiatus in pregnant women with stress urinary incontinence detected by transperineal three-dimensional ultrasound].

OBJECTIVE: To identify the morphological characteristics of pelvic diaphragm hiatus in pregnant women with stress urinary incontinence (SUI) by transperineal three-dimensional (3-D) ultrasound. METHODS: From Oct. 2008 to Mar. 2009, 145 pregnant women (third trimester group) at 37-41 weeks of gestation underwent transperineal 3-D ultrasound investigation at Department of Obstetrics and Gynecology, the Sixth People's Hospital, Shanghai Jiaotong University, including 38 pregnant women with stress urinary incontinence (SUI) and the other 107 non SUI pregnant women. In the mean time, 50 normal nulliparous healthy women were chosen as control group. The morphological characteristics of pelvic diaphragm hiatus, the diameter of pelvic diaphragm hiatus, pubovisceral muscle thickness and genitohiatal and levator ani angle were measured at rest, on maximum Valsalva and maximum pelvic floor contraction by 3-D ultrasound, respectively. RESULTS: Loosen connective tissue and pubococcygeus avulsion were observed in some pregnant women at third trimester. The area of pelvic diaphragm hiatus were (15.2+/-1.9), (16.4+/-2.0) and (13.6+/-1.9) cm2, pubovisceral muscle thickness were (0.72+/-0.11), (0.68+/-0.14) and (0.77+/-0.11) cm, levator ani angle were (60+/-8) degrees, (57+/-10) degrees and (64+/-14) degrees at rest, on maximum Valsalva and maximum pelvic floor contraction respectively. These parameters were significantly increased than those in control group [(11.2+/-2.6), (14.5+/-4.5) and (9.2+/-2.6) cm2; (0.66+/-0.10), (0.67+/-0.14) and (0.71+/-0.14) cm; (50+/-4) degrees, (51+/-5) degrees and (46+/-5) degrees] at three maneuvers, respectively (P<0.05). And those parameters of the anteroposterior hiatal diameter, lateral hiatal diameter, perimeter of pelvic diaphragm hiatus and area of pelvic diaphragm hiatus in SUI pregnant women were increased than those in non SUI pregnant women at three maneuvers, respectively (P<0.05). Pubovisceral muscle thickness in SUI pregnant women was significantly lower than that in non SUI pregnant women at maximum pelvic floor contraction (P<0.05), but there were not significant difference between SUI and non SUI pregnant women at rest and on maximum Valsalva in pubovisceral muscle thickness and genitohiatal and levator ani angle (P>0.05). CONCLUSIONS: Pelvic floor anatomic remodeling is identified in late pregnant women. When compared with non pregnant women, the loosen pelvic floor connective tissue and the bigger diameters of pelvic diaphragm are observed in late pregnant women. It is observed that the increased diameters of pelvic diaphragm and decreased thickness of pubovisceral muscle in later pregnant SUI women than those in non SUI pregnant women.

[Insulin release and daily glucose change in polycystic ovary syndrome women with normal glucose tolerance].

OBJECTIVE: To evaluate the characteristics of daily glucose change, insulin sensitivity, and insulin release in polycystic ovary syndrome (PCOS) women with normal glucose tolerance. METHODS: Oral glucose tolerance test (OGTT) with 75 g glucose was conducted on 20 PCOS women with normal glucose tolerance and 20 age-matched healthy women with normal menstruation. Before the glucose uptake and 30, 60, and 120 min after samples of venous blood were collected to detect the blood glucose and insulin. Continuous glucose monitoring system (CGMS) was used to monitor the glucose concentration of subcutaneous interstitial fluid so as to reflect the blood glucose level. Mean blood glucose level (MBG) and its standard deviation (SDBG), mean amplitude of glycemic excursion (MAGE), peak level of postprandial plasma glucose as well as its peaking time during a 48-hour period CGMS were calculated. Stumvoll first-phase and second-phase (1st PH and 2nd PH) insulin release during OGTT were evaluated by Stumvoll formula, whereas baseline insulin release by HOMA-B. Insulin sensitivity index (ISI) was evaluated by Cederholm formula. RESULTS: (1) The 1-hour and 3-hour plasma glucose levels during OGTT of the PCOS group were higher than those of the control group (P < 0.01 and P < 0.05 respectively). The fasting insulin level and insulin levels 30, 60, 120, and 180 min after the glucose uptake during OGTT of the PCOS group were all significantly higher than those of the control group (all P < 0.01). (2) The daily MBG, SDBG, and MAGE of the PCOS group were (5.43 +/- 0.44), (0.66 +/- 0.24), and (1.46 +/- 0.47) mmol/L respectively, all similar to those of the control group [(5.3 +/- 0.5), (0.67 +/- 0.27), and (1.7 +/- 0.7) mmol/L respectively, all P > 0.05]. The peaking time of post-breakfast plasma glucose level of the PCOS group was (40 +/- 18) min, significantly longer than that of the control group [(30 +/- 10) min, P < 0.05]. (3) The ISI of the PCOS group was 64 (59 - 81), significantly lower than that of the control group [95 (78 - 102), P < 0.01]. The Stumvoll 1st PH and 2nd PH insulin release levels of the PCOS group were 1779 (1411 - 2194) mU/L and 440 (361 - 545) mU/L respectively, both significantly higher than those of the control group [1217 (1056 - 1477) and 320 (283 - 375) mU/L respectively, P < 0.01 and P < 0.05]. CONCLUSION: With normal glucose tolerance, the PCOS women show (1) a backwardly-shifted peak of glucose -stimulated insulin secretion, (2) an abnormal mode of daily glucose change characterized by a delayed peak of post-breakfast plasma glucose level, and (3) significant decrease of peripheral insulin sensitivity with compensated increase of insulin secretion.

Ratios of biochemical markers in peritoneal fluid to those in venous blood for the diagnosis of ruptured tubal pregnancy: A prospective study.

OBJECTIVES: Ectopic pregnancies are among the leading causes of maternal morbidity and mortality in both developed and emerging nations, but tests for early, accurate, and convenient detection are lacking. STUDY DESIGN: Between January 2013 and February 2015, 504 women with tubal pregnancy were prospectively recruited, and their clinical characteristics were recorded. Samples of peritoneal fluid were collected by culdocentesis, and venous blood was drawn from the antecubital vein. In samples from each source, levels of the following biochemical markers were measured: cancer antigen 125 (CA125), human chorionic gonadotropin (hCG), progesterone, vascular endothelial growth factor, and creatine kinase. RESULTS: The ratios of biochemical markers in the peritoneal fluid and in the blood (Rp/v) were calculated. The median of Rp/v-CA125 and Rp/v-hCG were significantly lower in the ruptured ectopic pregnancy group than in the unruptured group. The optimal cutoff value to detect ectopic pregnancy rupture was 401.5U/mL as the upper limit for peritoneal CA125, with a sensitivity of 93.5% and specificity of 74.2%. The optimal cutoff value was 18.7 as the upper limit in the peritoneal fluid/blood ratio (Rp/v) of CA125, with a sensitivity of 77.5% and specificity of 68.4%. CONCLUSIONS: In countries with poor access to laparoscopy, culdocentesis is useful. In this study, culdocentesis provided additional information for management of abdominal pain when laparoscopy is not available. The authors propose Rp/v cutoff values that can be used conveniently and quickly to diagnose ruptured ectopic pregnancies and bleeding, enabling rapid and appropriate therapeutic responses.

Cholesterol Synthetase DHCR24 Induced by Insulin Aggravates Cancer Invasion and Progesterone Resistance in Endometrial Carcinoma.

3ß-Hydroxysteroid-Δ24 reductase (DHCR24), the final enzyme of the cholesterol biosynthetic pathway, has been associated with urogenital neoplasms. However, the function of DHCR24 in endometrial cancer (EC) remains largely elusive. Here, we analyzed the expression profile of DHCR24 and the progesterone receptor (PGR) in our tissue microarray of EC (n = 258), the existing EC database in GEO (Gene Expression Omnibus), and TCGA (The Cancer Genome Atlas). We found that DHCR24 was significantly elevated in patients with EC, and that the up-regulation of DHCR24 was associated with advanced clinical stage, histological grading, vascular invasion, lymphatic metastasis, and reduced overall survival. In addition, DHCR24 expression could be induced by insulin though STAT3, which directly binds to the promoter elements of DHCR24, as demonstrated by ChIP-PCR and luciferase assays. Furthermore, genetically silencing DHCR24 inhibited the metastatic ability of endometrial cancer cells and up-regulated PGR expression, which made cells more sensitive to progestin. Taken together, we have demonstrated for the first time the crucial role of the insulin/STAT3/DHCR24/PGR axis in the progression of EC by modulating the metastasis and progesterone response, which could serve as potential therapeutic targets for the treatment of EC with progesterone receptor loss.

RelB/NF-κB links cell cycle transition and apoptosis to endometrioid adenocarcinoma tumorigenesis.

Dysfunction of nuclear factor-κB (NF-κB) signaling has been causally associated with numerous human malignancies. Although the NF-κB family of genes has been implicated in endometrial carcinogenesis, information regarding the involvement of central regulators of NF-κB signaling in human endometrial cancer (EC) is limited. Here, we investigated the specific roles of canonical and noncanonical NF-κB signaling in endometrial tumorigenesis. We found that NF-κB RelB protein, but not RelA, displayed high expression in EC samples and cell lines, with predominant elevation in endometrioid adenocarcinoma (EEC). Moreover, tumor cell-intrinsic RelB was responsible for the abundant levels of c-Myc, cyclin D1, Bcl-2 and Bcl-xL, which are key regulators of cell cycle transition, apoptosis and proliferation in EEC. In contrast, p27 expression was enhanced by RelB depletion. Thus, increased RelB in human EC is associated with enhanced EEC cell growth, leading to endometrial cell tumorigenicity. Our results reveal that regulatory RelB in noncanonical NF-κB signaling may serve as a therapeutic target to block EC initiation.

Levonorgestrel intrauterine system versus thermal balloon ablation for the treatment of heavy menstrual bleeding: A meta-analysis of randomized controlled trials.

At present, there have been no standard research outcomes as to whether the levonorgestrel intrauterine system (LNG-IUS) or thermal balloon ablation (TBA) is superior for the treatment of patients suffering from heavy menstrual bleeding (HMB). Therefore, in the present study, a meta-analysis of randomized controlled trials (RCTs) was conducted in order to compare the effectiveness and affordability of the LNG-IUS with TBA in the treatment of HMB. A literature search of the following electronic databases was conducted: PubMed, EMBASE, the Cochrane Library, Google Scholar, the Chinese Scientific Journals Database, and the China National Knowledge Infrastructure; and a statistical analysis was performed using RevMan 5.2 software. Seven RCTs involving 467 patients (235 LNG-IUS, 232 TBA) met the inclusion criteria for the present study. As assessed by pictorial blood loss assessment chart (PBAC) scores, the LNG-IUS significantly reduced menstrual bleeding after 24 months [standardized mean difference (SMD), -0.86; 95% confidence interval (CI), -1.22 to -0.50; P<0.00001]. Furthermore, the total treatment cost of the LNG-IUS was lower than that of TBA (SMD, -2.35; 95% CI, -2.98 to -1.72; P<0.00001). However, at the 24 month follow-up, side effects such as amenorrhea occurred more frequently in patients treated with the LNG-IUS, as compared with TBA (relative risk, 2.49; 95% CI, 1.46-4.25; P=0.0008). No significant differences in hemoglobin levels and quality of life were demonstrated between the two treatment groups. The results of the present meta-analysis suggest that the LNG-IUS may be more effective and affordable than TBA as a long-term treatment (24 months) for HMB. However, following 12-24 months of treatment, side effects such as amenorrhea may be more frequent in patients treated with the LNG-IUS. When considering short-term treatment for HMB, controversy remains regarding the two methods and further studies are required to precisely evaluate the outcomes.

Pulsatility index in combination with biomarkers or mean arterial pressure for the prediction of pre-eclampsia: Systematic literature review and meta-analysis.

INTRODUCTION: Our objective was to perform a meta-analysis examining the sensitivity of pulsatility index (PI) and various biomarkers and PI and mean arterial pressure (MAP) for the prediction of pre-eclampsia. MATERIAL AND METHODS: PubMed, CENTRAL, and Embase databases were searched from inception until 8 May 2014 using combinations of the search terms: pre-eclampsia, ultrasonography, pregnancy, biomarker, mean arterial pressure, placental protein 13, pregnancy-associated plasma protein-A, placental growth factor, activin A, inhibin A, pulsatility index. The pooled sensitivity of PI + biomarkers and PI + MAP were calculated, and reported with corresponding 95% confidence intervals (CIs). RESULTS: Fifteen studies were included in the meta-analysis. The pooled sensitivity of all biomarkers for the prediction of pre-eclampsia was 0.669 (95% CI 0.610-0.723), for the prediction of early-onset pre-eclampsia was 0.830 (95% CI 0.794-0.861), and for the prediction of late-onset pre-eclampsia was 0.564 (95% CI 0.499-0.627). Similarly, the predictive ability of PI + MAP for early-onset pre-eclampsia was good (sensitivity 0.894), while that for late-onset was poor (sensitivity 0.570). CONCLUSION: The combination of PI and different biomarkers or MAP exhibits a good predictive ability for early-onset pre-eclampsia, and poor predictive ability for late-onset pre-eclampsia.

Prognostic value of Musashi-1 in endometrioid adenocarcinoma.

AIMS: Musashi-1, a RNA-binding protein, is suggested to be a cancer stem cell-related marker; its high level of protein expression is reported to be associated with high histological grade in some tumors. The aim of this study was to investigate the prognostic value of Musashi-1 in patients with endometrioid adenocarcinoma (EAC). METHODS: We examined the Musashi-1 mRNA expression level in 35 fresh EAC tissue samples and 15 normal endometrium samples by real-time RT-PCR, and its protein expression level in 148 paraffin EAC tissue samples and 20 paraffin normal endometrium samples by immunohistochemistry. The correlation between Musashi-1 and overall survival (OS) used Cox proportional hazards regression. The prognostic accuracy of Musashi-1 compared with other clinicopathological risk factors by logistic regression. Furthermore, we examined whether Musashi-1 expression is correlated with another cancer stem cell marker CD133 by real-time RT-PCR. RESULTS: Musashi-1 mRNA expression of EAC is 2.8-fold higher than that of normal endometrium (P=0.0009). Musashi-1 protein expression level is correlated with tumor stage, grade and vascular invasion. Patients with higher protein expression level of Musashi-1 are associated with poor survival rate than those with negative or low level of expression (HR=2.073, P=0.001). The area under the curve (AUC) for Musashi-1 is 0.8, which is higher than other clinicopathological factors (P=0.000). In addition, Musashi-1 mRNA expression seems to be closely correlated with CD133 expression (r=0.7167, P<0.0001). CONCLUSIONS: Our results suggest high level of Musashi-1 protein expression is associated with poor survival in EAC patients, which may be an independent prognostic factor for EAC.

Screening for characteristic microRNAs between pre-invasive and invasive stages of cervical cancer.

The aim of the present study was to investigate the characteristic microRNAs (miRNAs) expressed during the pre-invasive and invasive stages of cervical cancer. A gene expression profile (GSE7803) containing 21 invasive squamous cell cervical carcinoma samples, 10 normal squamous cervical epithelium samples and seven high-grade squamous intraepithelial cervical lesion samples, was obtained from the Gene Expression Omnibus. Differentially expressed genes (DEGs) were identified using significance analysis of microarray software, and a Gene Ontology (GO) enrichment analysis was conducted using the Database for Annotation, Visualization and Integrated Discovery. The miRNAs that interacted with the identified DEGs were selected, based on the TarBase v5.0 database. Regulatory networks were constructed from these selected miRNAs along with their corresponding target genes among the DEGs. The regulatory networks were visualized using Cytoscape. A total of 1,160 and 756 DEGs were identified in the pre-invasive and invasive stages of cervical cancer, respectively. The results of the GO enrichment demonstrated that the DEGs were predominantly involved in the immune response and the cell cycle, in the pre­invasive and invasive stages, respectively. Furthermore, a total of 18 and 26 characteristic miRNAs were screened in the pre­invasive and invasive stages, respectively. These miRNAs may be potential biomarkers and targets for the diagnosis and treatment of the different stages of cervical cancer.

[Relationship between left ventricular diastolic function and plasma brain natriuretic peptide concentration during severe pregnancy-induced hypertension syndrome].

OBJECTIVE: To evaluate the relationship between the left ventricular diastolic function and plasma level of plasma brain natriuretic peptide (BNP) among patients with pregnancy-induced hypertension (PIH) syndrome. METHODS: The left ventricular diastolic function was evaluated by Doppler echocardiography, and plasma BNP level was tested by radioimmunoassay among 36 pregnant women with severe PIH, 32 normal pregnant women, and 21 normal non-pregnant women of childbearing age. RESULTS: The parameters such as peak mitral flow velocity in early diastole (E), E-wave velocity-time integral (EVTI), the ratio of peak mitral flow velocity in early diastole and peak A-wave velocity in late diastole (E/A), peak pulmonary venous diastolic forward flow velocity (D) and D-wave velocity-time integral (DVTI) of the 36 severe PIH patients were significantly lower than those of the 32 normal pregnant women and those of the 21 normal non-pregnant women of child-bearing age. But the parameters such as A, A-wave velocity integral (AVTI), and peak pulmonary venous diastolic forward flow velocity (AR) were significantly higher than those of the normal pregnant women and those of the normal non-pregnant women of child-bearing age. E/A ratio, D and DVTI of the normal pregnant women were significantly lower than those of the normal non-pregnant women of child-bearing age, however, A, AVTI, S/D, and AR were significantly higher than those of the normal non-pregnant women of child-bearing age. The BNP concentration of the normal pregnant women was significantly higher than that of the normal non-pregnant women of childbearing age, but significantly lower than that of the severe PIH patients. There were significant correlations between left ventricular diastolic function variables (E/A ratio and AR) and BNP concentration in normal pregnant women and in PIH patients. CONCLUSION: The left ventricular diastolic function is slightly damaged in normal pregnant women and significantly damaged in patients with severe PIH. The plasma BNP level of pregnant women can become an excellent index to predict their left ventricular diastolic function.

Correlation between the overexpression of epidermal growth factor receptor and mesenchymal makers in endometrial carcinoma.

OBJECTIVE: The objective of this study was to evaluate the effect of overexpression of epidermal growth factor receptor (EGFR) on the expression of epithelial cell markers (E-cadherin and α-catenin) and mesenchymal cell markers (N-cadherin and vimentin) in endometrial carcinoma. METHODS: The expression of all 4 markers was evaluated in EGFR overexpressing Ishikawa cells, control Ishikawa cells, and KLE cells using reverse transcription polymerase chain reaction (RT-PCR) and Western blotting. The expression of these 4 markers was also determined in cancerous tissues of patients with endometrial carcinoma using immunohistochemical staining. RESULTS: Ishikawa cells transfected with EGFR showed decreased expression of E-cadherin and α-catenin and increased expression of N-cadherin and vimentin compared with control Ishikawa cells (p<0.01 for all). The expression of N-cadherin and vimentin was higher and the expression of E-cadherin and α-catenin was lower in stage II-III than stage I and in grade II-III than grade I endometrial carcinoma tissue (p<0.01 for all). CONCLUSION: Decreased expression of epithelial markers (E-cadherin and α-catenin) and increased expression of mesenchymal markers (N-cadherin and vimentin) were observed in human endometrial carcinoma tissue. These findings correlate with high EGFR expression in cultured endometrial carcinoma cells.

Rictor is an independent prognostic factor for endometrial carcinoma.

Early-stage endometrial carcinoma (EC) patients have a high cure rate; however, those with high-risk factors may have poor prognosis. Thus, there is an urgent need for searching for new prognostic molecules to more accurately predict survival of patients. We detected the Rictor mRNA expression level in 30 fresh EC tissue and 17 normal endometrial tissue samples with real-time quantitative RT-PCR and Rictor protein expression level in 134 (test cohort) and 115 (validation cohort) paraffin tissue samples by immunohistochemistry, analyzed the correlation between variables and overall survival (OS) using Cox proportional hazards regression, compared the prognostic accuracy of Rictor with other clinicopathological risk factors by logistic regression. The results showed that Rictor mRNA expression of EC is higher than that of normal endometrium; Rictor protein expression level was closely correlated with FIGO stage, grade and vascular invasion in both cohorts; a univariate analysis showed that the pathological type, stage, grade, vascular invasion, lymphatic metastasis and Rictor were predictors of OS in both cohorts; furthermore, multivariate Cox proportional hazards regression analysis indicated that vascular invasion and Rictor were independent prognostic factors for EC in both cohorts; an ROX curve comparison showed that the area under the curve (AUC) for Rictor combined with other clinicopathological prognostic factors was higher than any individual factor or other clinicopathological prognostic factors' combination. Based on the above data, we concluded that Rictor is an independent prognostic factor for EC. It combined with other clinicopathological risk factors was a stronger prognostic model than individual risk factor or their combination.

Weighted gene co-expression network analysis in identification of endometrial cancer prognosis markers.

OBJECTIVE: Endometrial cancer (EC) is the most common gynecologic malignancy. Identification of potential biomarkers of EC would be helpful for the detection and monitoring of malignancy, improving clinical outcomes. METHODS: The Weighted Gene Co-expression Network Analysis method was used to identify prognostic markers for EC in this study. Moreover, underlying molecular mechanisms were characterized by KEGG pathway enrichment and transcriptional regulation analyses. RESULTS: Seven gene co-expression modules were obtained, but only the turquoise module was positively related with EC stage. Among the genes in the turquoise module, COL5A2 (collagen, type V, alpha 2) could be regulated by PBX (pre-B-cell leukemia homeobox 1)1/2 and HOXB1(homeobox B1) transcription factors to be involved in the focal adhesion pathway; CENP-E (centromere protein E, 312kDa) by E2F4 (E2F transcription factor 4, p107/p130-binding); MYCN (v-myc myelocytomatosis viral related oncogene, neuroblastoma derived [avian]) by PAX5 (paired box 5); and BCL-2 (B-cell CLL/ lymphoma 2) and IGFBP-6 (insulin-like growth factor binding protein 6) by GLI1. They were predicted to be associated with EC progression via Hedgehog signaling and other cancer related-pathways. CONCLUSIONS: These data on transcriptional regulation may provide a better understanding of molecular mechanisms and clues to potential therapeutic targets in the treatment of EC.

Coagulation and fibrinolysis related cytokine imbalance in preeclampsia: the role of placental trophoblasts.

OBJECTIVE: Cytokine imbalance might have a pivotal role in hypercoagulability seen in preeclampsia. Our objective was to determine the relationship of blood coagulation related factors in placental tissue and peripheral blood in preeclamptic and normal pregnancies. METHODS: We compared mRNA and protein levels of tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), and tissue factor (TF) in the placenta of normal and preeclamptic pregnancies. Placental and peripheral blood t-PA and PAI-1 levels were examined. Trophoblasts were used to study the effects of hypoxia, hypoxia-reperfusion, and inflammatory cytokines on t-PA, PAI-1, tissue factor pathway inhibitor (TFPI), and TF. RESULTS: PAI-1 and TF mRNA and protein levels were higher in placental tissue of preeclamptic pregnancies and in the peripheral blood of patients with preeclampsia. mRNA and protein secretion of TF, TFPI, PAI-1, but not t-PA, was increased in trophoblast cell culture under hypoxia and hypoxia-reoxygenation. Cell cultures with high levels of tumor necrosis factor-alpha (TNF-alpha) exhibited increased expression and secretion of TF and PAI-1, decreased TFPI, and no significant change of t-PA. CONCLUSIONS: Imbalanced synthesis of t-PA, PAI-1, TFPI, and TF in trophoblasts may contribute to hypercoagulability in patients with preeclampsia.