Comparison of two 3D reconstruction models for understanding of complicated female pelvic tumors.

OBJECTIVE: Three-dimensional (3D) reconstructed models have been shown to improve visualization in complex female pelvic tumors. Cinematic rendering (CR) is a 3D imaging technique for computed tomography (CT) images, which creates more realistic images with the ability to enhance imaging of anatomical features for diagnosis. This study was set up to compare two types of 3D models and to validate the use of 3D anatomical techniques for the diagnosis of complex female pelvic tumors. METHODS: The preclinical, randomized, two-sequence crossover investigation was performed from December 2022 to January 2023 at First Affiliated Hospital of Chongqing Medical University. Sixteen residents and 10 attending surgeons assessed the cases of 23 patients with two types of 3D model images. The surgeons were randomly assigned to two assessment sequences (CR-3D model group and CT-3D model group). For each case, participants selected one question that probed fundamental questions about the tumor's genesis throughout each assessment period. Following a 4-week washout period, case assessments were transferred to the other image modality. RESULTS: The main result assessment was the accuracy of the answers. The time to answer the questions and the case assessment questionnaire was added as a secondary outcome. The mean scores in the CR-3D models (19.35 ± 1.87) varied significantly from those in the CT-CR group (16.77 ± 1.8) (P < 0.001), and solving the questions in the CT-3D model sequence (41.96 ± 6.31 s) varied significantly from that in the CR-3D model sequence (52.88 ± 5.95 s) (P < 0.001). Subgroup analysis revealed that there were statistically significant variations in the scores of female reproductive tumors, pelvic tumors other than the reproductive system, and retroperitoneal tumors (P = 0.005). Analysis of the assessment questionnaire showed that more surgeons choose CR 3D reconstruction (8.31 ± 0.76 vs 7.15 ± 1.19, P < 0.001). CONCLUSIONS: The results suggest that each 3D reconstruction method has its own advantages. Surgeons feel that CR reconstruction models are a useful technique that can improve their comprehension of complex pelvic tumors, while traditional 3D models have an advantage in terms of speed to diagnosis.

The crucial value of serum ferritin in assessing high-risk factors and prognosis for patients with endometrial carcinoma.

BACKGROUND: Endometrial carcinoma is a common malignant tumor in female reproductive system. At present, there is no effective and economic prognostic index. This study aimed to investigate the effect of serum ferritin levels on the prognosis of endometrial carcinoma. METHODS: Data of 367 patients who diagnosed with endometrial carcinoma at the First Affiliated Hospital of Chongqing Medical University between January 2012 and August 2018 was retrospectively analyzed. The prediction accuracy was evaluated by receiver operating characteristics curves and Youden's J statistics. Hosmer-lemeshow test was used to confirm the goodness of fit of the model. The prognostic value of serum ferritin on disease free survival (DFS) and overall survival (OS) of endometrial carcinoma was evaluated by univariate log-rank tests and multivariate cox regression models. RESULTS: Preoperative high serum ferritin was correlated with older age, high grade, specific histological subtypes and recurrence of endometrial carcinoma (P < 0.05). The DFS and OS of 198 patients with elevated serum ferritin levels were significantly lower than those with low serum ferritin levels (P = 0.001 and P = 0.002, respectively). In multivariate analysis, serum ferritin was an independent prognostic factor for DFS and OS in endometrial carcinoma (P = 0.012, P = 0.028). CONCLUSION: Through our research, we found that the high expression of serum ferritin level was not only related to low DFS and OS in patients with endometrial carcinoma, but also related to the high-risk factors of endometrial carcinoma recurrence. So serum ferritin levels may be used to predict the poor prognosis of patients with endometrial carcinoma.

Prediction of Prognosis, Immunotherapy and Chemotherapy with an Immune-Related Risk Score Model for Endometrial Cancer.

Endometrial cancer (EC) is the most common gynecologic cancer. The overall survival remains unsatisfying due to the lack of effective treatment screening approaches. Immunotherapy as a promising therapy has been applied for EC treatment, but still fails in many cases. Therefore, there is a strong need to optimize the screening approach for clinical treatment. In this study, we employed co-expression network (GCN) analysis to mine immune-related GCN modules and key genes and further constructed an immune-related risk score model (IRSM). The IRSM was proved effective as an independent predictor of poor prognosis. The roles of IRSM-related genes in EC were confirmed by IHC. The molecular basis, tumor immune microenvironment and clinical characteristics of the IRSM were revealed. Moreover, the IRSM effectiveness was associated with immunotherapy and chemotherapy. Patients in the low-risk group were more sensitive to immunotherapy and chemotherapy than those in the high-risk group. Interestingly, the patients responding to immunotherapy were also more sensitive to chemotherapy. Overall, we developed an IRSM which could be used to predict the prognosis, immunotherapy response and chemotherapy sensitivity of EC patients. Our analysis not only improves the treatment of EC but also offers targets for personalized therapeutic interventions.

The value of serum HE4 and CA125 levels for monitoring the recurrence and risk stratification of endometrial endometrioid carcinoma.

To evaluate the role of serum human epididymis secretory protein 4 (HE4) and carbohydrate antigen 125 (CA125) levels for predicting and monitoring the recurrence of endometrial endometrioid carcinoma (EEC) and assessing preoperative risk stratification in EEC patients. A total of 434 EEC patients were selected for this retrospective study between May 2011 and August 2018. Serum HE4 and CA125 levels were analyzed before the initial treatment, at the first postoperative follow-up, and at recurrence or the last follow-up. Patients were risk stratified according to the European Society for Medical Oncology (ESMO), European Society for Radiotherapy & Oncology (ESTRO) and European Society of Gynaecological Oncology (ESGO) guideline. We compared the ability of these biomarkers for prediction and monitoring by performing receiver operating characteristic curve analysis and identified optimal cut-off values by determining the Youden index. Kaplan-Meier analyses were also performed to determine prognostic value. Preoperative serum HE4 was identified as a significant predictor for the recurrence of EEC (p = 0.014). Preoperative serum HE4 and CA125 levels were related to depth of myometrial invasion, lymph node status and FIGO stage. Serum HE4 and CA125 levels were both statistically significant markers for monitoring the recurrence of EEC (P = 0.000 for each biomarker). When combined, the two markers showed higher levels of sensitivity and specificity. The two biomarkers were also significant biomarkers for evaluating the risk stratification of patients undergoing lymphadenectomy (P = 0.000 for each biomarker). For premenopausal stage I patients, preoperative serum HE4 and CA125 levels were significant predictors of the need for ovarian preservation (P = 0.000 and P = 0.002, respectively). For premenopausal patients with stage I intramucosal differentiation, preoperative serum levels of HE4 were significant predictors for fertility preservation (P = 0.024). Preoperative serum HE4 level can be used to predict the recurrence of EEC. Postoperative serum HE4 and CA125 levels can be used to monitor the recurrence of EEC and are more sensitive when combined. Preoperative serum levels of CA125 and HE4 levels are of significant value for risk stratification in EEC patients.

[Overexpression of chicken Klf2 promotes klf7 transcription and inhibits adipocyte differentiation].

Overexpression of Krüppel like factor 2 (Klf2) or Klf7 inhibits adipocyte formation. However, it remains unclear whether Klf2 regulates klf7 expression in adipose tissue. In this study, oil red O staining and Western blotting were employed to study the effect of Klf2 overexpression on the differentiation of chicken preadipocytes. The results showed that Klf2 overexpression inhibited the differentiation of chicken preadipocytes induced by oleate and the expression of pparγ, while promoted klf7 expression in chicken preadipocytes. Spearman correlation analysis was used to study the correlation between the expression data of klf2 and klf7 in the adipose tissue of both human and chicken. The results showed that there was a significantly positive correlation between the expression of klf2 and klf7 in adipose tissues (r > 0.1). Luciferase reporter assay showed that overexpression of Klf2 significantly promoted the activity of chicken klf7 promoter (-241/-91, -521/-91, -1 845/-91, -2 286/-91, -1 215/-91; P < 0.05). In addition, the activity of klf7 promoter (-241/-91) reporter in chicken preadipocytes was significantly positively correlated with the amount of klf2 overexpression plasmid transfected (Tau=0.917 66, P=1.074×10-7). Moreover, Klf2 overexpression significantly promoted the mRNA expression of klf7 in chicken preadipocytes (P < 0.05). In conclusion, upregulation of klf7 expression might be one of the pathways that Klf2 inhibits chicken adipocyte differentiation, and the sequence from -241 bp to -91 bp upstream chicken klf7 translation start site might mediate the regulation of Klf2 on klf7 transcription.

Clinical Factors and Perinatal Outcomes Associated With Short Latency Period in Twin Pregnancies With Preterm Premature Rupture of Membranes Before 34 Weeks: A Retrospective Study.

Background: There is a lack of literature on short latency period (SLP) in twin pregnancies with preterm premature rupture of membranes (PPROM). Thus, the aim of this study was to identify the clinical factors and perinatal outcomes associated with SLP in twin pregnancies with PPROM and to establish a predictive model to identify SLP. Methods: Twin pregnancies with PPROM between 24 0/7 and 33 6/7 weeks were included and a retrospective analysis was performed. Patients were divided into two groups based on the latency period after PPROM: Group 1 ≤24 h (defined as SLP) and Group 2 >24 h (defined as long latency period, LLP), the clinical factors and perinatal outcomes were compared between the two groups. Binary logistic regression and receiver operating characteristic curve analyses were used to identify the independent clinical factors associated with latency period after PPROM and assess the predictive accuracy for SLP. Results: 98 and 92 pregnant women had short and long latency period, respectively. Prolonged latency significantly increased the occurrence of chorioamnionitis. Neonatal outcomes were not affected by latency duration after PPROM. Binary regression analysis revealed that higher gestational age (GA) at PPROM (P = 0.038), presence of uterine contractions (P < 0.001), Bishop score > 4 (P = 0.030), serum procalcitonin levels ≥0.05 ng/mL upon admission, and absence of use of tocolytic agents (P < 0.001) were significant independent predictors of a SLP. A predictive model developed using these predictors had an area under the curve (AUC) of 0.838, and the presence of uterine contractions alone had an AUC of = 0.711. Conclusion: Uterine contraction was the most important prognosticator for a SLP. A latency period of >24 h was associated with chorioamnionitis, but adverse neonatal outcomes were not observed.

The Preeminent Value of the Apparent Diffusion Coefficient in Assessing High-Risk Factors and Prognosis for Stage I Endometrial Carcinoma Patients.

OBJECTIVES: To evaluate the role of the apparent diffusion coefficient (ADC) value in the individualized management of stage I endometrial carcinoma (EC). METHODS: A retrospective analysis was performed on 180 patients with stage I EC who underwent 1.5-T magnetic resonance imaging. The mean ADC (mADC), minimum ADC (minADC), and maximum ADC (maxADC) values of each group were measured and compared. We analyzed the relationship between ADC values and stage I EC prognosis by Kaplan-Meier method and Cox proportional hazards analysis. RESULTS: Patients with lower ADC values were more likely to be characterized by higher grades, specific histological subtypes and deeper myometrial invasion. The mADC, minADC and maxADC values (×10-3 mm2/s) were 1.045, 0.809 and 1.339, respectively, in grade 1/2 endometrioid carcinoma with superficial myometrial invasion, which significantly differed from those in grade 3 or nonendometrioid carcinoma or with deep myometrial invasion (0.929, 0.714 and 1.215) (P=<0.001, <0.001 and <0.001). ADC values could be used to predict these clinicopathological factors. Furthermore, the group with higher ADC values showed better disease-free survival and overall survival. CONCLUSIONS: The present study indicated that ADC values were associated with the high-risk factors for stage I EC and to assess whether fertility-sparing, ovarian preservation or omission of lymphadenectomy represent viable treatment options. Moreover, this information may be applied to predict prognosis. Thus, ADC values could contribute to managing individualized therapeutic schedules to improve quality of life.

Perinatal outcomes of twin pregnancies with preterm premature rupture of the membranes at 24-34 weeks' gestation.

To describe the perinatal outcomes of twin pregnancies with preterm premature rupture of membranes (PPROM) before 34 weeks' gestation and identify factors associated with discharge without severe or moderate-severe neonatal morbidity. This study was conducted as a retrospective analysis of twin pregnancies with PPROM occurring at 24 0/7 to 33 6/7 weeks' gestation. Perinatal outcomes were assessed by gestational age (GA) at PPROM and compared between PPROM and non PPROM twins. Factors associated with discharge without severe or moderate-severe neonatal morbidity were identified using logistic regression analysis. Of the 180 pregnancies (360 foetuses), only 17 (9.4%) women remained pregnant 7 days after PPROM. There were 10 (2.8%) cases of prenatal or neonatal death; 303 (84.2%) and 177 (49.2%) neonates were discharged without severe or moderate-severe morbidity, respectively. As GA at PPROM increased, the adverse obstetric and neonatal outcomes decreased, especially after 32 weeks. There was no significant difference in general neonatal outcomes between PPROM and non PPROM twins. The GA at PPROM and latency period were both significantly associated with discharge without severe or moderate-severe neonatal morbidity. Pregnancy complications and 5-min Apgar score < 7 increased severe neonatal morbidity. As GA at PPROM increased, the risk of adverse perinatal outcomes decreased. GA at PPROM and latency period were significantly associated with discharge without severe or moderate-severe neonatal morbidity.

Serum HE4 and CA125 combined to predict and monitor recurrence of type II endometrial carcinoma.

There is no recognized serum biomarker to predict the recurrence of endometrial carcinoma (EC). We aimed to explore serum human epididymis protein 4 (HE4) and cancer antigen 125 (CA125) as the biomarkers to predict and monitor recurrence of type II EC. 191 patients diagnosed with type II EC were involved for this retrospective study. Comparing recurrent with non-recurrent patients, HE4 levels resulted a statistically significant difference at primary diagnosis and recurrence, respectively (P = 0.002 and P = < 0.001), while CA125 levels resulted statistically significant (P = < 0.001) at recurrence. According to receiver operating characteristic curve analysis, the areas under the curve were significant for HE4 levels at primary diagnosis and recurrence predicting recurrence. Furthermore, CA125 levels at recurrence were significant. And the combination of both markers showed the higher sensitivity and specificity than single one. Patients with higher HE4 levels were associated with worse disease-free survival and overall survival, the opposite was true for patients with lower HE4 levels. The preoperative HE4 levels could be used to evaluate the risk factors of type II EC. Which suggested that HE4 levels might associated with the prognosis of type II EC. And combination of HE4 and CA125 could be applied to monitor recurrence during follow-up.

Diagnostic Value of Preoperative CA125, LDH and HE4 for Leiomyosarcoma of the Female Reproductive System.

PURPOSE: Leiomyosarcoma (LMS) is a rare and extremely aggressive malignancy that is derived from or shows evidence of differentiation toward smooth muscle. If LMS occurs in the female reproductive system, preoperative diagnosis can be difficult, as LMS is easily mistaken for a uterine leiomyoma, especially a degenerated uterine fibroid (DUF). Thus, we assessed the diagnostic value of the preoperative serum concentrations of cancer antigen 125 (CA125), lactate dehydrogenase (LDH) and human epididymis protein 4 (HE4) for differentiating LMS from DUF. PATIENTS AND METHODS: We enrolled patients with LMS or DUF who were receiving treatment in The First Affiliated Hospital of Chongqing Medical University between 2009 and 2020. If the preoperative serum concentrations of CA125, LDH and HE4 of our study participants had been tested, these data were analyzed. The preoperative serum concentrations of CA125, LDH and HE4 in participants with LMS (n = 37) were compared with those of participants with pathologically diagnosed DUF (n = 102), who served as the control group. RESULTS: The preoperative serum concentrations of CA125, LDH and HE4 of participants with LMS of the female reproductive system were significantly higher than those of participants with DUF (P = 0.009, P < 0.001, P = 0.001, respectively). The cut-off preoperative serum concentrations of CA125, LDH and HE4 were 30.85 U/mL, 186.50 U/L and 50.50 pmol/L, respectively. When these three parameters were used for an analysis of their combined diagnostic utility, the area under the curve (AUC) was 0.892, the sensitivity was 68.4% and the specificity was 95.1% (P < 0.001). CONCLUSION: A combined analysis of the preoperative serum concentrations of CA125, LDH and HE4 could be a promising method for diagnostically differentiating LMS of the female reproductive system from DUF.

Relationship between ascites volume and clinical outcomes in epithelial ovarian cancer.

OBJECTIVE: Ascites is a tumor microenvironment, ascites and massive ascites-induce compression could promote the progression of epithelial ovarian cancer (EOC); however, the impact of ascites volume on clinical outcomes has not been studied extensively. We aimed to investigate the association between ascites volume and clinical outcomes especially platinum resistance in EOC. METHODS: We retrospectively evaluated a total of 546 EOC patients with respect to the amount of ascites, clinicopathologic factors, and survival. Using the threshold of 1500 ml to classify patients into small- and large-volume ascites groups, we analyzed the correlation between ascites volume and clinicopathological factors, including platinum-free interval (PFI), and prognosis. RESULTS: Patients with large volume ascites were more likely to present with later stage disease, primary platinum-resistant (PPR) cancer, and suboptimal cytoreduction. Prolonged PFI was associated with decreased ascites volume. The large-volume ascites group showed worse progression-free survival (PFS) and overall survival (OS). An increase in ascites volume was associated with an increased risk of disease recurrence (hazard ratio [HR] = 1.115, 95% confidence interval [CI]: 1.035-1.200) and death (HR = 1.213, 95% CI: 1.090-1.350). CONCLUSIONS: Ascites was an independent predictor of PFS and OS in EOC patients. A large volume of ascites predicated a shortened PFI, an increased incidence of PPR and suboptimal cytoreduction. Thus, the volume of ascites is a simply available clinical parameter, which could be used to evaluate the prognosis and platinum resistance of EOC patients early, it contributes to formulate individualized treatment plan and improve the outcome of EOC patients.

Prognostic Value of Ki-67 Index in Patients With Endometrial Stromal Sarcoma.

OBJECTIVE: The Ki-67 index is used to evaluate cell proliferation activity, which is related to tumor progression, metastasis, and prognosis. We aimed to explore the prognostic value of Ki-67 index in endometrial stromal sarcoma and to explore the optimal cut-off value of Ki-67 index for predicting recurrent endometrial stromal sarcoma. METHODS: A total of 82 patients with endometrial stromal sarcoma who were treated in our hospital were collected. Clinicopathological data of these patients were retrospectively analyzed. Ki-67 index was detected by the immunohistochemical method. Receiver operating characteristic curve and the Youden index were performed to determine the optimal cut-off value of Ki-67 index for predicting recurrent endometrial stromal sarcoma. The Cox regression was performed to analyze risk factors affecting prognosis of endometrial stromal sarcoma. The Kaplan-Meier method and Log-rank test were performed to analyze the survival of patients. RESULTS: The optimal cut-off value of Ki-67 index for predicting recurrent endometrial stromal sarcoma was 35%. The results of univariate analysis showed that high Ki-67 index (≥35%) was statistically significantly bound up with shorter progress free survival and overall survival. The results of multivariate analysis showed that Ki-67 index (P = 0.001) and ovarian preservation (P = 0.040) were independent prognostic factors of progress free survival. CONCLUSIONS: A Ki-67 index cut-off of 35% was optimal for predicting recurrent endometrial stromal sarcoma. Ki-67 index may be a useful prognostic marker in endometrial stromal sarcoma.

The prominent value of apparent diffusion coefficient in assessing high-risk factors and prognosis for patients with endometrial carcinoma before treatment.

BACKGROUND: To date, there are no consensus methods to evaluate the high-risk factors and prognosis for managing the personalized treatment schedule of patients with endometrial carcinoma (EC) before treatment. Apparent diffusion coefficient (ADC) is regarded as a kind of technique to assess heterogeneity of malignant tumor. PURPOSE: To explore the role of ADC value in assessing the high-risk factors and prognosis of EC. MATERIAL AND METHODS: A retrospective analysis was made on 185 patients with EC who underwent 1.5-T magnetic resonance imaging (MRI). Mean ADC (mADC), minimum ADC (minADC), and maximum ADC (maxADC) were measured and compared in different groups. RESULTS: Among the 185 patients with EC, the mADC and maxADC values in those with high-risk factors (type 2, deep myometrial invasion, and lymph node metastasis) were significantly lower than in those without. According to receiver operating characteristic (ROC) curve analysis, the areas under the curve (AUC) were significant for mADC, minADC, and maxADC predicting high-risk factors. Furthermore, the AUCs were significant for mADC and maxADC predicting lymph node metastasis but were not significant for minADC. Patients with lower mADC were associated with worse overall survival and disease-free survival; the opposite was true for patients with higher mADC. CONCLUSION: Our study showed that ADC values could be applied to assess the high-risk factors of EC before treatment and might significantly relate to the prognosis of EC. It might contribute to managing initial individualized treatment schedule and improve outcome in patients with EC.

Researches on the Correlation Between Estrogen and Progesterone Receptors Expression and Disease-Free Survival of Endometrial Cancer.

OBJECTIVE: In this study, 345 patients with endometrial carcinoma (EC) were selected to investigate the correlation between ER/PR status and the EC disease-free survival (DFS) rate. METHODS: The intensity and proportion of tumor cell expression of estrogen receptors and progesterone receptors (ER/PR) status of 345 postoperative tumor specimens in ECs were independently assessed semi-quantitatively by two pathologists using immunohistochemistry, the summed score ranged from 0 to 8 points was worked out by adding proportion score and intensity score based on the breast cancer hormone receptor immunohistochemical Allred scoring system. The association between DFS in ECs and ER/PR expression (intensity, proportion and summed score) was assessed using Cox regression analysis. Gene expression data were obtained from The Cancer Genome Atlas research network (TCGA). RESULTS: According to inclusion criteria, 201 type I and 144 type II EC patients were enrolled in this study. In the univariate analysis of type I endometrial carcinoma, the intensity, proportion and summed score of ER/PR status were significantly correlated with DFS. After adjusting for factors known to significantly impact survival, the influence of ER/PR status on DFS is generally decreased but the correlation is still significant. In the univariate analysis of type II endometrial carcinoma, the intensity, proportion and summed score of ER/PR status were significantly correlated with DFS. After adjusting for factors known to significantly impact survival, the influence of ER status on DFS is generally decreased, but the correlation is still significant, the effect of PR expression on DFS is not statistically significant. CONCLUSION: Higher ER/PR expression status was associated with better DFS in patients with type I endometrial cancer after adjusting for known factors that significantly affect survival. In patients with type II endometrial cancer, patients with positive ER expression were significantly associated with better DFS. However, the effect of PR expression on DFS was not statistically significant.

Clinicopathologic factors associated with short-term survival in advanced epithelial ovarian cancer.

BACKGROUND: Epithelial ovarian cancer (EOC) is the most lethal gynaecological malignancy, and there is a deficiency of information in the literature on the early recognition of short-term survivor (STS). This study aimed to identify the clinicopathological factors associated with STS in late-stage EOC and to establish a predictive model to identify STS. METHODS: Selected patients with International Federation of Gynecology and Obstetrics (FIGO) stage III or IV EOC were included in the study, and a retrospective analysis was performed. The characteristics of the patients who survived not more than 2 years (STS) were compared to those who survived at least 2 years (defined as long-term survivors, LTS). Binary logistic regression and receiver operating characteristic curve (ROC) were used to identify the independent prognostic factors associated with EOC and assess the predictive accuracy for STS. RESULTS: We identified 254 patients with advanced EOC including 57 STS and 197 LTS. A univariate analysis revealed that STS had a tendency to have omental metastasis and larger tumor size, to be platinum resistant, to have non-serous histology, to undergo suboptimal cytoreduction, to have comorbidity, and to undergo primary chemotherapy less than 6 courses. Binary regression analysis revealed that tumor size (P=0.033), platinum resistance (P<0.001), non-serous histology (P=0.048) and number of primary chemotherapy (P=0.028) were significant independent predictors of STS. A developed predictive model using these predictors had an AUC =0.831; platinum resistance alone had an AUC =0.732. CONCLUSIONS: Tumor size, omental metastasis, platinum resistance, non-serous histology, and number of primary chemotherapy are predictors associated with STS when controlling other confounding factors. Tumor size and omental metastasis may be considered novel, important prognostic factors for advanced EOC patients. Platinum resistance was the most important prognosticator for STS; hence, more work is needed for the early identification and treatment of these EOC patients.

DACT1 Overexpression in type I ovarian cancer inhibits malignant expansion and cis-platinum resistance by modulating canonical Wnt signalling and autophagy.

Type I epithelial ovarian cancer (EOC) is primarily resistant to platinum-based chemotherapies and needs novel therapeutics. Given the aberrant Wnt activation in type I EOC and the involvement of Dapper1 Antagonist of Catenin-1 (DACT1) in Wnt signalling, the role of DACT1 in tumourigenesis of type I EOC was evaluated. Firstly, all tested EOC cell lines and primary EOC tissues, especially type I EOC, were observed to have significantly lower DACT1 expression than normal controls. Next, 3AO cells, which arise from a patient with primary mucinous EOC and express low endogenous levels of DACT1, were transfected with a lentivirus carrying full-length DACT1 (3AO-DACT1), grew slower and formed smaller tumours in nude mice compared to 3AO-NC. Furthermore, 3AO-DACT1 had lower levels of key mediators of canonical Wnt signalling, Dvl2 and ß-catenin, GSK-3ß with phosphorylated Ser9, and the Wnt/ß-catenin target genes, with significantly lower nuclear ß-catenin levels. Additionally, 3AO-DACT which contained higher levels of lipidated LC3 (LC3-II) and Beclin1, but lower levels of p62/SQSTM1, were more sensitive to cis-platinum. And chloroquine partially rescued its cis-platinum resistance. We identified DACT1 as a negative regulator in type I EOC, protecting against malignant expansion by inhibiting canonical Wnt signalling and cis-platinum resistance by regulating autophagy.

NEDD9 overexpression is associated with the progression of and an unfavorable prognosis in epithelial ovarian cancer.

Neural precursor cell-expressed, developmentally down-regulated 9 (NEDD9), a scaffolding protein, has been identified as a prometastatic and poor prognostic gene in multiple malignant tumors. However, the potential role of the NEDD9 protein in epithelial ovarian cancer (EOC) remains unclear. In the present study, we investigated the expression of NEDD9 and the correlation between NEDD9 expression and prognosis in EOC. NEDD9 expression was detected in 129 archived EOC specimens by immunohistochemical staining and in 28 freshly frozen EOC specimens by Western blotting. The expression of NEDD9 was evaluated in ovarian cancer cell lines by Western blotting and immunofluorescence. The association between the expression of NEDD9 and prognosis was determined by survival analysis. Results suggested that NEDD9 was overexpressed in EOC specimens compared with noninvasive epithelial ovarian tumors and normal ovarian specimens. A high level of NEDD9 expression significantly correlated with advanced-stage tumors (International Federation of Gynecology and Obstetrics classes III-IV, P < .001), high-grade carcinoma (grades 2-3, P < .001), and suboptimal primary cytoreductive surgery (residual disease <1cm, P = .021). The expression level of NEDD9 varied in ovarian cancer cell lines. Multivariate analysis indicated that NEDD9 overexpression (P = .033), advanced stage (P < .001), and high-grade carcinoma (P = .01) were independent predictors of poor survival. In conclusion, NEDD9 is overexpressed and associated with an unfavorable prognosis in EOC. NEDD9 overexpression is an independent factor of poor prognosis and may serve as a potential biomarker in EOC.

WAVE1 gene silencing via RNA interference reduces ovarian cancer cell invasion, migration and proliferation.

OBJECTIVE: Wiskott-Aldrich syndrome protein family verprolin-homologous protein 1 (WAVE1) has been implicated in cancer cell migration and invasion. We have previously shown that the overexpression of WAVE1 in epithelial ovarian cancer (EOC) tissues is associated with a poor prognosis. However, the mechanism of WAVE1 regulating the malignant behaviors in EOC remains unclear. METHODS: In the present study, we knocked down WAVE1 expression in SKOV3 and OVCAR-3 cells through RNA interference to detect the cell biology and molecular biology changes. Moreover, western-blot was used to investigate the underlying mechanism of WAVE1 regulating the proliferative and invasive malignant behaviors in ovarian cancer cells. RESULTS: The down-regulation of WAVE1 had a significant effect on cell morphological changes. WAVE1 silencing decreased cell migration, cell invasion, cell adhesion, colony formation and cell proliferation in vitro. In addition, we found that down-regulation of WAVE1 inhibited malignant behaviors in vivo. Furthermore, our study also indicated that the PI3K/AKT and p38MAPK signaling pathways might contribute to WAVE1 promotion of ovarian cancer cell proliferation, migration, and invasion. CONCLUSIONS: WAVE1 might promote the proliferative and invasive malignant behaviors through the activation of the PI3K/AKT and p38MAPK signaling pathways in EOC.

In vitro effects of SB202190 on Echinococcus granulosus.

Spillage of cyst contents during surgical operation is the major cause of recurrence after hydatid cyst surgery. Instillation of a scolicidal agent into a hepatic hydatid cyst is the most commonly employed measure to prevent this complication. SB202190 is a pyridinyl imidazole derivative and is known to be a specific inhibitor of p38 MAPK. In the present study, the scolicidal effect of SB202190 was investigated. Freshly isolated Echinococcus granulosus protoscolices were subjected to SB202190 treatment (10, 20, 40, and 80 µM), and the effects on parasite viability were monitored by trypan blue staining. Corresponding effects were visualized by scanning and transmission electron microscopy. Dose-dependent protoscolex death within a few days of SB202190 treatment was observed. Although the in vitro scolicidal effect of SB202190 was satisfactory, the in vivo efficacy of this drug and also possible side effects remain to be further investigated.