LncRNA IDH1-AS1 sponges miR-518c-5p to suppress proliferation of epithelial ovarian cancer cell by targeting RMB47

Long noncoding RNA(lncRNA)IDH1 antisense RNA 1(IDH1-AS1)is involved in the progression of multiple cancers,but its role in epithelial ovarian cancer(EOC)is unknown.Therefore,we investigated the expression levels of IDH1-AS1 in EOC cells and normal ovarian epithelial cells by quantitative real-time PCR(qPCR).We first evaluated the effects of IDH1-AS1 on the proliferation,migration,and invasion of EOC cells through cell counting kit-8,colony formation,EdU,transwell,wound-healing,and xenograft assays.We then explored the downstream targets of IDH1-AS1 and verified the results by a dual-luciferase reporter,qPCR,rescue experiments,and Western blotting.We found that the expression levels of IDH1-AS1 were lower in EOC cells than in normal ovarian epithelial cells.High IDH1-AS1 expression of EOC patients from the Gene Expression Profiling Interactive Analysis database indicated a favorable prognosis,because IDH1-AS1 inhibited cell proliferation and xenograft tumor growth of EOC.IDH1-AS1 sponged miR-518c-5p whose overexpression promoted EOC cell proliferation.The miR-518c-5p mimic also reversed the proliferation-inhibiting effect induced by IDH1-AS1 overexpression.Furthermore,we found that RNA binding motif protein 47(RBM47)was the downstream target of miR-518c-5p,that upregulation of RBM47 inhibited EOC cell proliferation,and that RBM47 overexpressing plasmid counteracted the proliferation-promoting effect caused by the IDH1-AS1 knockdown.Taken together,IDH1-AS1 may suppress EOC cell proliferation and tumor growth via the miR-518c-5p/RBM47 axis.

Epithelial Ovarian Cancer Patients and Clinicopathological Features and Survival: A Comparison of Outcomes of Two Age Cohorts in Bangladesh

Objective: This study compared the clinicopathologic characteristics and overall survival of epithelial ovarian carcinoma in women younger versus older than 45 years in Bangladesh. Methods: A retrospective analysis identified 129 epithelial ovarian carcinoma patients who were admitted to the National Institute of Cancer Research and Hospital, in Dhaka, Bangladesh from 2016 through 2017 for surgery. These patients were grouped into two categories: the younger group (≤45 years) and the older group (>45 years). Clinicopathological features of epithelial ovarian carcinoma were analyzed in each age group. Cox proportional hazards model identified factors affecting survival and Kaplan-Meier survival curves with log rank test compared outcomes for each age group. Results: The median age of the 129 women was 46 years (IQR: 38, 56) and median time of follow-up was 9 months (inter-quartile range: 4, 26.5). We found a significant difference in the CA-125 level (p < 0.044), age of menopause (p < 0.001), follow-up duration (p < 0.016), disease outcome (p < 0.005) and histopathological type (p < 0.021) between the two groups. No significant differences were found in breakdown of Federation of Gynecology and Obstetrics (FIGO) stage of the disease. There was a significant difference in overall survival between the patients of two groups (p = 0.021) where there was a higher probability of death among the older cohort. The 5-year overall survival rates for the younger age versus older group were 34.0%, and 11.7% respectively. Independent prognostic factors by univariate analysis for the overall survival were age, FIGO stage, preoperative CA-125 and CEA level. However, when controlling for stage, survival was similar between age cohorts. Conclusions: Our data suggests that women in Bangladesh with epithelial ovarian cancer who are under the age of 45 years have a different clinical profile and better overall survival than women in the older age cohort.

Efficacy of Bispecific Antibody Targeting EpCAM and CD3 for Immunotherapy in Ovarian Cancer Ascites:An Experimental Study

Objective This study aimed to explore the value of M701,targeting epithelial cell adhesion molecule(EpCAM)and CD3,in the immunotherapy of ovarian cancer ascites by the in vitro assay.Methods The expression of EpCAM in ovarian cancer tissues was analyzed by databases.The EpCAM expression and immune cell infiltration in different foci of ovarian cancer were detected by 8-channel flow cytometry.The toxic effect of M701 on OVCAR3 was tested using the in vitro cytotoxicity assay.The 3D cell culture and drug intervention experiments were performed to evaluate the therapeutic effect of M701 in ovarian cancer specimens.Flow cytometry was used to examine the effect of M701 on the binding of immune cells to tumor cells and the activation capacity of T cells.Results The results of the bioinformatic analysis showed that the expression of EpCAM in ovarian cancer tissue was significantly higher than that in normal ovarian tissue.The 8-channel flow cytometry of clinical samples showed that the EpCAM expression and lymphocyte infiltration were significantly heterogeneous among ovarian cancer patients and lesions at different sites.The in vitro experiment results showed that M701 had a significant killing effect on OVCAR3 cells.M701 also obviously killed primary tumor cells derived from some patients with ovarian cancer ascites.M701 could mediate the binding of CD3^(+)T cells to EpCAM^(+)tumor cells and induce T cell activation in a dose-dependent manner.Conclusion M701 showed significant inhibitory activity on tumor cells derived from ovarian cancer ascites,which had a promising application in immunotherapy for patients with ovarian cancer ascites.

Overexpression and Immunosuppressive Functions of Transforming Growth Factor 1,Vascular Endothelial Growth Factor and Interleukin-10 in Epithelial Ovarian Cancer

Objective： Transforming growth factor-1 （TGF-βI）, vascular endothelial growth factor （VEGF）, and interleukin-lO （IL-10） may be critical cytokines in the microenvironment of a tumor, playing roles in immune suppression. This study was conducted to elucidate the roles and immunosuppressive functions of these cytokines in epithelial ovarian cancer （EOC）. Methods： The expression levels of TGF-β1, VEGF and IL-10 in malignant tissue were evaluated by immune- histochemistry and compared with corresponding borderline, benign, and tumor-free tissues. Moreover, relationships among the levels of these cytokines and correlations between expression and the prognosis of EOC were analyzed by Pearson rank correlations and multi-factor Logistic regression. The roles of TGF-βI, VEGF, and IL-lO in the immunosuppressive microenvironment of ovarian cancer were studied through dendritic cell （DC） maturation and CD4＋CD25＋FoxP3＋ Treg generation in vitro experiments. Results： TGF-β1, VEGF, and IL-IO were expressed TGF-β1 was an independent prognostic factor for EOC n 100%, 74.69%, and 54.96% of EOC patients, respectively. L-IO was significantly co-expressed with VEGF. In vitro, VEGF and TGF-β31 strongly interfered with DC maturation and consequently led to immature DCs, which secreted high levels of IL-IO that accumulated around the tumor site. TGF-β1 and IL-10 induced Treg generation without antigen presentation in DCs. Conclusions： TGF-βI, VEGF and IL-IO play important roles in EOC and can lead to frequent immune evasion events.

PGC-la induces apoptosis in human epithelial ovarian cancer cells through a PPARy-dependent pathway

Peroxisome proliferator-activated receptor gamma （PPAR）,） coactivator-1 alpha （PGC-1α） coactivates multiple transcription factors and regulates several metabolic processes. The current study investigated the role of PGC-1α in the induction of apoptosis in human epithelial ovarian cancer cells. The PGC-1α mRNA level between human ovaries and human ovarian epithelial tumors was examined by quantitative RT-PCR. Less PGC- 1α expression was found in the surface epithelium of malignant tumors compared with normal ovaries. Overexpression of PGC-1α in human epithelial ovarian cancer cell line Ho-8910 induced cell apoptosis through the coordinated regulation of Bcl-2 and Bax expression. Microarray analyses confirmed that PGC-1α dramatically affected the apoptosis-related genes in Ho-8910 cells. Mitochondrial functional assay showed that the induction of apoptosis was through the terminal stage by the release of cytochrome c. Furthermore, PG-C- 1 α-induced apoptosis was partially, but not completely, blocked by PPAR）, antagonist （GW9662）, and suppression of PPAR）, expression by siRNA also inhibited PGC-1α-induced apoptosis in Ho-8910 cells. These data suggested that PGC-1α exerted its effect through a PPARγ-dependent pathway. Our findings indicated that PGC-1α was involved in the apoptotic signal transduction pathways and downregulation of PGC-1α may be a key point in promoting epithelial ovarian cancer growth and progression.

Association of serum lipids and severity of epithelial ovarian cancer：an observational cohort study of 349 Chinese patients

While obesity and fat intake have been associated with the risk and prognosis of epithelial ovarian cancer, the association between the lipid levels and epithelial ovarian cancer phenotype remains controversial. We conducted a retrospective study of 349 epithelial ovarian cancer patients who received treatment at Jiangsu Cancer Hospital, China between 2011 and 2017. We analyzed age at diagnosis, blood pressure, plasma glucose content, body mass index（BMI）, lipid levels and clinical parameters. Severity of epithelial ovarian cancer was classified according to the International Federation of Gynecology and Obstetrics（FIGO） grading system. Univariate analysis of the clinical factors according to the severity of epithelial ovarian cancer was followed by logistic regression analysis to identify clinical factors significantly associated with epithelial ovarian cancer severity. Univariate analysis indicated that age,BMI, triglyceride（TG）, and high density lipoproteins（HDL） differed significantly among different stages of epithelial ovarian cancer（P〈0.05）. In the logistic regression model, elevated TG（OR： 1.883; 95% CI= 1.207-2.937）, and low HDL（OR： 0.497; 95% CI = 0.298-0.829） levels were significantly associated with the high severity epithelial ovarian cancer. Our data indicate that high TG and low HDL levels correlate with a high severity of epithelial ovarian cancer. These data provide important insight into the potential relationship between the lipid pathway and epithelial ovarian cancer phenotype and development.

Establishment of an optimized CTC detection model consisting of EpCAM,MUC1 and WT1 in epithelial ovarian cancer and its correlation with clinical characteristics

Objective:Emerging studies have demonstrated the promising clinical value of circulating tumor cells(CTCs)for diagnosis,disease assessment,treatment monitoring and prognosis in epithelial ovarian cancer.However,the clinical application of CTC remains restricted due to diverse detection techniques with variable sensitivity and specificity and a lack of common standards.Methods:We enrolled 160 patients with epithelial ovarian cancer as the experimental group,and 90 patients including 50 patients with benign ovarian tumor and 40 healthy females as the control group.We enriched CTCs with immunomagnetic beads targeting two epithelial cell surface antigens(EpCAM and MUC1),and used multiple reverse transcription-polymerase chain reaction(RT-PCR)detecting three markers(EpCAM,MUC1 and WT1)for quantification.And then we used a binary logistic regression analysis and focused on EpCAM,MUC1 and WT1 to establish an optimized CTC detection model.Results:The sensitivity and specificity of the optimized model is 79.4%and 92.2%,respectively.The specificity of the CTC detection model is significantly higher than CA125(92.2%vs.82.2%,P=0.044),and the detection rate of CTCs was higher than the positive rate of CA125(74.5%vs.58.2%,P=0.069)in early-stage patients(stage I and II).The detection rate of CTCs was significantly higher in patients with ascitic volume≥500 mL,suboptimal cytoreductive surgery and elevated serum CA125 level after 2 courses of chemotherapy(P<0.05).The detection rate of CTC;and CTC;was significantly higher in chemo-resistant patients(26.3%vs.11.9%;26.4%vs.13.4%,P<0.05).The median progression-free survival time for CTC;patients trended to be longer than CTC;patients,and overall survival was shorter in CTC;patients(P=0.043).Conclusions:Our study presents an optimized detection model for CTCs,which consists of the expression levels of three markers(EpCAM,MUC1 and WT1).In comparison with CA125,our model has high specificity and demonstrates better diagnostic values,especially for early-stage ovarian cancer.Detection of CTC;and CTC;had predictive value for chemotherapy resistance,and the detection of CTC;suggested poor prognosis.

Expression and mechanism of action of miR-196a in epithelial ovarian cancer

Objective:To explore the expression,biological function and possible mechanism of action of microRNA molecular-196a(miR-196a) in epithelial ovarian cancer.Methods:RT-PCR was used to detect the expression quantities of epithelial ovarian tissue,benign ovarian tissue,normal ovary epithelial tissue,ovarian cancer cell lines and miR-196 a in normal ovarian epithelial cells to analyze the relationship between the expression of miR-196 a and the clinical pathologic parameters of ovarian cancer.Among those cell lines,the cell line of which miR-196 a expressed the most or least was selected and transfected the ovarian cancer cell line by using negative control plasma and miR-196 a inhibitor.After transfection,RT-PCR was used to test the expression quantity of miR-196 a,Transwell chamber method was applied to determine the migration and invasion abilities of ovarian carcinoma cells and Western blot was employed to detect the expression of HOXA10 protein.Results:The relative expression quantities of miR-196 a in ovarian cancer tissue and benign ovarian tissue were significantly higher than that in normal ovarian epithelial tissue,and the expression quantity of miR-196 a in ovarian cancer tissue was distinctively higher than that in benign ovarian tissue(P < 0.05).Among 78 cases of epithelial ovarian cancer,the expression quantities of miR-196 a in patients with low differentiation were all significantly higher than those in patients with high differentiation(P< 0.05).The expression of miR-196 a showed no significant relation with age,clinical stage and whether CA125 was positive or not in patients(P > 0.05).Compared with normal ovarian epithelial cell line IOSE80,the expression quantities of miR-196 a of all ovarian cancer cell lines increased obviously and differences were statistically significant(P < 0.05).Among them,the expression of miR-196 a of ovarian cancer cell line SKOV3 was the highest,while it decreased significantly(4.678 ± 0.785 vs.2.131 ± 0.345,t = 2.938,P < 0.05) after the ovarian cancer cell line SKOV3 was transfected by miR-196 a inhibitor.The results of Transwell chamber method showed that the migration and invasion abilities of ovarian cancer cells SKOV3 were declined significantly after the expression of miR-196 a was down-regulated and the difference showed statistical significance(P < 0.05).The results of Western blot revealed that the relative expression of HOXA10 decreased distinctly after the expression of miR-196 a was down-regulated and also the difference showed statistical significance(P < 0.05).Conclusions:The miR-196 a might serve as a cancer-promoting gene to promote the migration and invasion of epithelial ovarian cancer by downstream target gene HOXA10.

Prognosis in epithelial ovarian cancer: Clinical analysis of 287 pelvic and para-aortic lymphadenectomy

Objective: To evaluate the relationship between the pelvic and para-aortic lymphadenectomy and the prognosis of epithelial ovarian cancer. Methods: 287 patients suffering from primary epithelial ovarian cancer from 1995 to 2005 were analyzed retrospectively. Results: The 3-, 5-, 10-year survival with systematic lymphadenectomy (SL) were slightly higher than those without SL, but there were no statistically significance (P > 0.05). The 3-, 5-, 10-year survival of clinical stages without SL were lower than those with SL, but there were no significant difference either (P > 0.05). The 3-,5-, and 10-year survival rates with SL were higher than those without SL with no statistically differences (P > 0.05) among the subgroups such as absent, ≤ 2 cm and > 2 cm residual tumor. The survival rates of the groups without residual tumor and the group with ≤ 2 cm residual tumor were significantly higher than that of > 2 cm (P < 0.005). On multivariate analysis, patient staging (P = 0.01) and size of residual disease after primary cytoreductive surgery (P < 0.001 and = 0.002, respectively) retained prognostic significance. SL was not proved to be an independent prognostic factor (P = 0.69). Conclusion: Systematic pelvic and para-aortic lymphadenectomy can not improve and prolong the survival time significantly.

Identification of Novel Epithelial Ovarian Cancer Biomarkers by Cross-laboratory Microarray Analysis

The purpose of this study was to pool information in epithelial ovarian cancer by combining studies using Affymetrix expression microarray datasets made at different laboratories to identify novel biomarkers.Epithelial microarray expression information across laboratories was screened and combined after preprocessing raw microarray data,then ANOVA and unpaired T test statistical analysis was performed for identifying differentially expressed genes(DEGs),followed by clustering and pathway analysis for these DEGs.In this work,we performed a combination analysis on microarrays from three different laboratories using gene expression data on ovarian cancer and obtained a list of differential expression profiles identified as potential candidate in aggressiveness of ovarian cancer.The clustering and pathway analysis explored the different molecular basis of different ovarian cancer stages and potential important regulatory pathways in ovarian cancer development.Our results showed that combination of microarray data from different laboratories in the same platforms may overcome biases derived from probe design and technical features,thereby accelerating the identification of trustworthy DEGs,and demonstrating the advantage of integrative analysis in gene expression studies on epithelial ovarian cancer research.

Pharmacology of cancer chemotherapy drugs for hyperthermic intraperitoneal peroperative chemotherapy in epithelial ovarian cancer

The peritoneal parietal and visceral surfaces of the abdomen and pelvis are an important anatomic site for the dissemination of epithelial ovarian cancer(EOC). The transcoelomic spread of cancer cells gives rise to peritoneal carcinomatosis(PC) which, without special treatments, is a fatal manifestation of EOC. In order to control PC cytoreductive surgery to remove macroscopic disease is combined with perioperative intraperitoneal(IP) and perioperative intravenous chemotherapy to eradicate microscopic residual disease. Chemotherapy agents are selected to be administered by the IP or intravenous route based on their pharmacologic properties. A peritoneal-plasma barrier which retards the clearance of high molecular weight chemotherapy from the peritoneal cavity results in a large exposure of small cancer nodules on abdominal and pelvic surfaces. Tissue penetration is facilitated by moderate hyperthermia(41-42 ℃) of the IP chemotherapy solution. Timing of the chemotherapy as a planned part of the surgical procedure to maximize expo-sure of all peritoneal surfaces is crucial to success.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in epithelial ovarian cancer: State of the art

Advanced stage epithelial ovarian cancer(EOC) is diffi cult to treat with low overall cure rates. A new strategy combining maximal cytoreductive surgery(CRS) with intraoperative hyperthermic intraperitoneal chemotherapy(HIPEC) has been proposed to treat advanced stage EOC in the primary setting. Numerous small, heterogeneous studies have been conducted exploring outcomes in patients with predominantly advanced, recurrent or refractory disease treated with CRS + HIPEC. Although morbidity rates approaching 35% have been reported, oncologic outcomes are promising. Incorporation of HIPEC for the treatment of primary EOC has continued to gain interest. Several prospective phase 2 clinical trials were recently completed evaluating the impact of CRS + HIPEC in the primary setting. This article will briefl y discuss the benefi ts of optimal surgical cytoreduction and the theoretical basis of intraperitoneal chemotherapy in patients with advanced stage EOC, and will then review existing literature describing oncologic outcomes in EOC patients treated with HIPEC in the primary setting.

Adaptor Protein Crk is Implicated in Mucus Formation in Mucinous Epithelial Ovarian Cancer (mEOC) Cells MCAS

Objective： The mucus production is an indicator for the histological grade of mucinous epithelial ovarian cancer （mEOC）. In our previous study, Crk expression was targeted in the human ovarian mucinous adenocarcinoma cell line MCAS through RNA interference, resulting in the establishment of Crk knock down cells. These cells exhibited decreased tumorigenic potential both in vitro and in vivo. The purpose of this study was to investigate if there is any change in the capability of forming mucus in these Crk knock down cells. Methods： Cytoplasmic periodic acid Schiff （PAS） staining and particle excluding assay were conducted to assess the mucus formation within and around cells, respectively. Additionally, the amount of mucus formed in tumor lumps from nude mice model was measured following HE and PAS staining. Results： The increased mucus production in Crk knockdown mEOC cells （MCAS） was manifested by increased number of enlarged cells filled with vacuoles-like mucus observed by phase-contrast microscope and cytoplasmic PAS staining; and enhanced mucus secretion was represented by the assembly of pericellular matrix in particle excluding assay and increased mucus area in tumor lumps from nude mice models. Conclusion： The course of carcinogenesis in mEOC is associated with the altered pattern of mucus production and secretion. The adaptor protein Crk is implicated in both pathways.

Comparative Study on Three Chemotherapeutic Regimens for the Treat-ment of Advanced Epithelial Ovarian Cancer

To investigate the best first-line chemotherapy regimen for the treatment of advanced ep- ithelial ovarian cancer (AEOC), the efficacy of three chemotherapy regimens for treatment of the pa- tients with AEOC in our hospital during Jan. 1992- Jan. 1999 was retrospectively analyzed. The therapeutic effects were compared with the supplement of Melphalan + Hexamethylme (PAM + HMM), cisplatin+ adriamycin+cyclophosphamide or isofamide (PAC) or cisplatin+cyclophospha- mide or isofamide (PC), Taxol+cisplatin (TP) combined chemotherapy after cytoreductive surgery. The results showed that the overall effective rate of TP was significantly higher than that of PAM+ HMM (P<0. 05); The complete remission rate of TP was significantly higher than that of PAM+ HMM and PAC or PC (all P<0. 05); The 2-year survival rate free of tumor of TP was obviously higher than that of PAM+HMM and PAC or PC(all P<0. 05). It was concluded that the therapeu- tic effect of TP regimen in the treatment of AEOC was better than PAM+HMM and PAC or PC and TP regimen could be recommended currently as the preferred first-line one for the treatment of AEOC.

Phosphorylation of Cofilin-1 Enhances Paclitaxel Resistance of Epithelial Ovarian Cancer Cells by Inhibiting Apoptosis

Objective To investigate the molecular mechanism of high phosphorylation levels of cofilin-1(p-CFL-1)associated with paclitaxel resistance in epithelial ovarian cancer(EOC)cells.Methods Cells displaying varying levels of p-CFL-1 and CFL-1 were created by plasmid transfection and shRNA interference.Cell inhibition rate indicating paclitaxel efficacy was assessed by Cell Counting Kit-8(CCK-8)assay.Apoptosis was assessed by flow cytometry and protein levels were detected by western blotting.Quantitative real-time polymerase chain reaction(qRT-PCR)was used to measure the expression levels of phosphokinases and phosphatases of CFL-1.Survival analysis evaluated the correlation between the prognosis of EOC patients and the levels of p-CFL-1 and slingshot-1(SSH-1).Results High levels of p-CFL-1 were observed in EOC cells that survived treatment with high doses of paclitaxel.SKOV3 cell mutants with upregulated p-CFL-1 showed impaired paclitaxel efficacy,as well as decreased apoptosis rates and pro-survival patterns of apoptosis-specific protein expression.Cytoplasmic accumulation of p-CFL-1 inhibited paclitaxel-induced mitochondrial apoptosis.SSH-1 silencing mediated CFL-1 phosphorylation in paclitaxel-resistant SKOV3 cells.Clinically,the high level of p-CFL-1 and the low level of SSH-1 in EOC tissues were closely related to chemotherapy resistance and poor prognosis in EOC patients.Conclusion The SSH-1/p-CFL-1 signaling pathway mediates paclitaxel resistance by apoptosis inhibition in EOC and is expected to be a potential prognostic predictor.

Adjuvant Chemotherapy May Not Be Necessary for Women with Stage IC1 Epithelial Ovarian Cancer

Objective:To determine whether adjuvant chemotherapy improves the prognoses in women with stage IC1 epithelial ovarian cancer(EOC).Methods:All eligible women diagnosed with stage IC1 EOC from 2003 to 2019 in Tongji Hospital were included.Patient characteristics,tumor features,surgical types,and chemotherapeutic treatments were collected.Kaplan-Meier analysis and Cox regression analysis were performed to evaluate progression-free survival(PFS)and overall survival(OS).

Mouse models of epithelial ovarian cancer for preclinical studies

Epithelial ovarian cancer(EOC) is the leading cause of gynecological cancer-related mortality in the developed world. EOC is a heterogeneous disease represented by several histological and molecular subtypes. Therefore, exploration of relevant preclinical animal models that consider the heterogenic nature of EOC is of great importance for the development of novel therapeutic strategies that can be translated clinically to combat this devastating disease. In this review, we discuss recent progress in the development of preclinical mouse models for EOC study as well as their advantages and limitations.

Expression of Bmi-1 and EZH2 in tissues adjacent to human epithelial ovarian cancer cells of orthotopic implantation in nude mice

Objective This study investigated the feasibility of screening residual normal ovarian tissues based on the expression of Bmi-1 and EZH2 in tissues adjacent to orthotopic ovarian carcinomas in nude mice. Methods The human epithelial ovarian cancer cell line OVCAR3 was grown in subcutaneous tissues and the tumor tissues were orthotopically implanted. The expression levels of Bmi-1 and EZH2 were detected by immunohistochemical staining and RT-PCR in cancer tissues, proximal and remote tissues with respect to the cancer tissues, and normal ovarian tissues of nude mice.Results Thirty-five ovarian tissue samples with normal biopsy results were obtained from 40 cases of human epithelial ovarian cancer in the nude mice in which the tumor tissues were orthotopically implanted. Bmi-1 and EZH2 expression levels were lower in proximal paraneoplastic tissue samples than in cancer tissue samples(P < 0.05) and higher than in remote paraneoplastic tissue samples(P < 0.01). No significant difference was found in the expression levels of Bmi-1 and EZH2 using immunohistochemistry among residual normal ovarian tissues obtained from orthotopically implanted models that differed in severity. The expression of Bmi-1 and EZH2 was negative in 20 normal ovarian tissue samples.Conclusion The expression levels of Bmi-1 and EZH2 were reduced with increasing distance from the cancer tissues. Negative expression of these tumor-associated genes can be used as a standard for the screening of normal ovarian tissues adjacent to tumor tissues. Normal ovarian tissues can be obtained from the tissues adjacent to tumors.

Correlation between epithelial ovarian cancer and thrombocytosis

Objective： To evaluate the clinical significance of platelet （PLT） count in epithelial ovarian cancer, and to investigate the correlation between thrombocytosis and the incidence of epithelial ovarian cancer. Methods： We evaluated 220 epithelial ovarian tumor patients divided into early stage epithelial ovarian cancer group （n = 80）, advanced stage epithelial ovarian cancer group （n = 50） and benign ovarian tumor group （n = 90） as controls, who underwent primary surgical treatment. Three groups were evaluated with the relationship between platelet counts and preoperative and postoperative CA125, histopathology, abdominal edema, residual tumor, and lymph node metastasis. Epithelial ovarian cancer patients were evaluated whether platelet count was decreased after surgery. Results： The mean platelet counts were （234.55 ± 71.51）× 10^9/L in the early stage epithelial ovarian cancer group, （308.12±111.95）× 10^9/L in the advanced stage epithelial ovarian cancer group, and （206.28± 52.62） × 10^9/L in the benign ovarian tumor group, with a significant difference among the 3 groups （P 〈 0.05）. In the early stage epithelial ovarian cancer group, the platelet count was correlated with histopathology. In the advanced stage epithelial ovarian cancer group, there was a correlation between thrombocytosis and the incidence of that residual tumor diameter was greater than 2 cm. But there was no relationship between platelet count and histopathology, CA125, abdominal edema, or lymph node metastasis. In general the platelet count was decreased after surgery. Conclusion： An increased platelet count is commonly seen in patients with epithelial ovarian cancer, but it usually decreases after surgery. Patients with thrombocytosis have poor prognosis. Platelet count can be used as a marker for the development and prognosis of epithelial ovarian cancer.

The optimal choice of chemotherapy regimens for patients with relapsed platinum-resistant epithelial ovarian cancer/primary peritoneal/fallopian tube cancer - protocol for a systematic review and network meta-analysis

Objective： Debulking surgery （residual disease of less than 1 cm） followed by platinum-taxane chemotherapy isthe current standard therapy for patients with epithelial ovarian cancer, primary peritoneal carcinoma and primaryfallopian cancer. But the prognosis remains poor. Several chemotherapy regimens could be selected for patientswith recrudescent cancer. However, the standard second chemotherapy regimen remains a subject of debate. Thepurpose of our study is to carry out a systematic review and network meta-analysis to compare the efficacy andsafety of different regimens for recurrent platinum-resistant ovarian cancer based on existing randomized controlledtrials （RCTs）. Methods and analysis： Medline, EMBASE, Cochrane Library and Cochrane Library databases,Science Citation Index Expanded, Conference Proceedings Citation Index-Science and ClinicalTrials.gov will besystematically searched for eligible studies. Randomized controlled trials （RCT） on chemotherapy, immune therapy,biological therapy, targeted therapy for recurrent platinum-resistant ovarian cancer with multiple outcome measureswill be included. The Cochrane Risk of Bias Tool will be used to assess the quality of included studies. The primaryoutcomes are overall survival and median survival time. The secondary outcomes include the safety and side effectsof these regimens. Direct meta-analysis and network meta-analysis （NMA） will be conducted to compare differentregimens. Conclusion： The results of this network meta-analysis will provide direct and indirect evidence oftreatments for recurrent platinum-resistant ovarian cancer, and it may provide a ranking of the chemotherapyregimens for patients and gynecological oncologists to help them select the best option.