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 ID...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.展开更多
BACKGROUND Low grade serous carcinoma of the ovary(LGSOC)is a rare type of epithelial ovarian cancer with a low incidence rate.The origin of ovarian cancer has always been a hot topic in gynecological oncology researc...BACKGROUND Low grade serous carcinoma of the ovary(LGSOC)is a rare type of epithelial ovarian cancer with a low incidence rate.The origin of ovarian cancer has always been a hot topic in gynecological oncology research,and some scholars believe that the origin of ovarian malignant tumors is the fallopian tubes.Primary fallopian tube cancer is the lowest incidence of malignant tumors in the female reproductive system.There are only a few reports in the literature,but the mortality rate is very high.But in clinical practice,fallopian tube cancer is very common,but in most cases,it is classified as ovarian cancer.CASE SUMMARY We report a 54 years old postmenopausal woman who was hospitalized with a lower abdominal mass and underwent surgical treatment.The final pathological confirmation was low-grade serous carcinoma of the right ovary and low-grade serous carcinoma of the left fallopian tube.No special treatment was performed after the surgery,and the patient was instructed to undergo regular follow-up without any signs of disease progression.CONCLUSION The prognosis of LGSOC is relatively good,over 80%of patients still experience disease recurrence.展开更多
The fatality rate of ovarian cancer (OC) is the highest, and the 5-year survival rate is only 50.8%. For more than 40 years, CA125 has been the most concerned and widely used biomarker of OC in clinical practice. In r...The fatality rate of ovarian cancer (OC) is the highest, and the 5-year survival rate is only 50.8%. For more than 40 years, CA125 has been the most concerned and widely used biomarker of OC in clinical practice. In recent years, many researchers have proposed a reliable strategy of multiple markers combined with CA125 to screen OC to make up for the lack of accuracy of CA125, redefine the biochemical recurrence threshold of CA125, and use mathematical model scores to provide help for the feasibility of treatment and survival prognosis. To fully understand the role of CA125 in OC screening, initial treatment, and recurrence prediction, and summarize the limitations of CA125, this review has summarized the new progress of CA125 in the diagnosis and treatment of OC in recent years which can also provide a reference for clinicians.展开更多
Despite significant effort and research funds, epithelial ovarian cancer remains a very deadly disease. There are no effective screening methods that discover early stage disease; the majority of patients are diagnose...Despite significant effort and research funds, epithelial ovarian cancer remains a very deadly disease. There are no effective screening methods that discover early stage disease; the majority of patients are diagnosed with advanced disease. Treatment modalities consist primarily of radical debulking surgery followed by taxane and platinum-based chemotherapy. Newer therapies including limited targeted agents and intraperitoneal delivery of chemotherapeutic drugs have improved disease-free intervals, but failed to yield longlasting cures in most patients. Chemotherapeutic resistance, particularly in the recurrent setting, plagues the disease. Targeting the pathways and mechanisms behind the development of chemoresistance in ovarian cancer could lead to significant improvement in patient outcomes. In many malignancies, including blood and other solid tumors, there is a subgroup of tumor cells, separate from the bulk population, called cancer stem cells(CSCs). These CSCs are thought to be the cause of metastasis, recurrence and resistance. However, todate, ovarian CSCs have been difficult to identify, isolate, and target. It is felt by many investigators that finding a putative ovarian CSC and a chemotherapeutic agent to target it could be the key to a cure for this deadly disease. This review will focus on recent advances in this arena and discuss some of the controversies surrounding the concept.展开更多
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 sup...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.展开更多
Objectives: To compare the survival and perioperafive morbidity between primary debulking surgery (PDS) and neoadjuvant chemotherapy followed by interval debulking surgery (NAC/IDS) in treating patients with adva...Objectives: To compare the survival and perioperafive morbidity between primary debulking surgery (PDS) and neoadjuvant chemotherapy followed by interval debulking surgery (NAC/IDS) in treating patients with advanced epithelial ovarian cancer (EOC). Methods: We retrospectively reviewed 67 patients with stage IIIC or iV EOC treated at Peking University Cancer Hospital from January 2006 to June 2009. VVherein, 37 and 30 patients underwent PDS and NAC/ IDS, respectively. Results: No difference in overall survival (OS) or progression-free survival (PFS) was observed between NAC/IDS group and PDS group (OS: 41.2 vs. 39.1 months, P=0.23; PFS: 27.1 vs. 24.3 months, P=0.37). The optimal debulking rate was 60% in the NAC/IDS group, which was significantly higher than that in the PDS group (32.4%) (P=0.024). The NAC/IDS group had significantly less intraoperative estimated blood loss and transfusion, lower nasogastric intubation rate, and earlier ambulation and recovery of intestinal function than the PDS group (P〈0.05). Conclusions: NAC/IDS is less invasive than PDS, and offers the advantages regarding optimal cytoreduction rate, intraoperative blood loss, and postoperative recovery, without significantly impairing the survival compared with PDS in treating patients with stage IIIC or IV EOC. Therefore, NAC/IDS may be a valuable treatment alternative for EOC patients.展开更多
Ovarian cancer is the leading cause of death in women with gynecological cancer. Most patients are diagnosed at an advanced stage and have a poor prognosis.Currently, surgical tumor debulking, followed by platinum- an...Ovarian cancer is the leading cause of death in women with gynecological cancer. Most patients are diagnosed at an advanced stage and have a poor prognosis.Currently, surgical tumor debulking, followed by platinum- and taxane-based chemotherapy is the standard treatment for advanced ovarian cancer. However, these patients are at great risk of recurrence and emerging drug resistance. Therefore, novel treatment strategies are required to improve outcomes for women with advanced ovarian cancer. A variety of molecular targeted agents, the majority of which are monoclonal antibodies and small-molecule protein-kinase inhibitors, have been explored in the management of ovarian cancer. The targets of these agents include angiogenesis, the human epidermal growth factor receptor family, ubiquitinproteasome pathway, epigenetic modulators, poly(ADPribose) polymerase (PARP), and mammalian target of rapamycin (mTOR) signaling pathway, which are aberrant in tumor tissue. The antiangiogenic agent, bevacizumab, has been reported as the most effective targeted agent and should be included in the standard chemotherapeutic regimen for advanced ovarian cancer. PARP inhibitors, which are mainly used in breast and ovarian cancer susceptibility gene-mutated patients, and mTOR inhibitors are also attractive treatment strategies, either alone or combination with chemotherapy, for ovarian cancer. Understanding the tumor molecular biology and identification of predictive biomarkers are essential steps for selection of the best treatment strategies. This article reviews the molecular mechanisms of the most promising targeted agents that are under early phase clinical evaluation for ovarian cancer.展开更多
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 rol...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.展开更多
Ovarian cancer is the second most common gyneco-logical cancer and the leading cause of death in the United States. In this article we review the diagnosis and current management of epithelial ovarian cancer which acc...Ovarian cancer is the second most common gyneco-logical cancer and the leading cause of death in the United States. In this article we review the diagnosis and current management of epithelial ovarian cancer which accounts for over 95 percent of the ovarian malignancies. We will present various theories about the potential origin of ovarian malignancies. We will discuss the genetic anomalies and syndromes that may cause ovarian cancers with emphasis on Breast cancer type 1/2 mutations. The pathology and pathogenesis of ovarian carcinoma will also be presented. Lastly, we provide a comprehensive overview of treatment strategies and staging of ovarian cancer, conclusions and future directions.展开更多
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 co...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.展开更多
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 cl...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.展开更多
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...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.展开更多
Objective The underlying mechanism of Ezrin in ovarian cancer(OVCA) is far from being understood.Therefore, this study aimed to assess the role of Ezrin in OVCA cells(SKOV3 and Ca OV3) and investigate the associated m...Objective The underlying mechanism of Ezrin in ovarian cancer(OVCA) is far from being understood.Therefore, this study aimed to assess the role of Ezrin in OVCA cells(SKOV3 and Ca OV3) and investigate the associated molecular mechanisms.Methods We performed Western blotting, reverse transcription-quantitative polymerase chain reaction, MTT, cell colony, cell wound healing, transwell migration and invasion, Rho A and Rac active pull down assays, and confocal immunofluorescence experiments to evaluate the functions and molecular mechanisms of Ezrin overexpression or knockdown in the proliferation and metastasis of OVCA cells.Results The ectopic expression of Ezrin significantly increased cell proliferation, invasiveness, and epithelial–mesenchymal transition(EMT) in OVCA cells. By contrast, the knockdown of endogenous Ezrin prevented OVCA cell proliferation, invasiveness, and EMT. Lastly, we observed that Ezrin can positively regulate the active forms of Rho A rather than Rac-1 in OVCA cells, thereby promoting robust stress fiber formation.Conclusion Our results indicated that Ezrin regulates OVCA cell proliferation and invasiveness by modulating EMT and induces actin stress fiber formation by regulating Rho-GTPase activity, which provides novel insights into the treatment of the OVCA.展开更多
Objective:To study the change of TIZ expression in epithelial ovarian cancer cells.Methods:HO8910 cells were transinfected with siRNA to inhibit the expression of TIZ.pcDNA3.1-TIZ vectors were combined to increase the...Objective:To study the change of TIZ expression in epithelial ovarian cancer cells.Methods:HO8910 cells were transinfected with siRNA to inhibit the expression of TIZ.pcDNA3.1-TIZ vectors were combined to increase the TIZ expression level.The cell viabilily,colony forming efficiency and cycle distribution of HO8910,HO8910/NC,HO8910/pcDNA3.1-NC,HO8910/ TIZ-573 and HO8910/pcDNA3.l-TIZ were compared,and the invasion rate,migration rate and adhesion rate between 5 groups of cells were compared.Results:Compared with those of HO8910,HO8910/NC and HO8910/pcDNA3.1-NC,the cell viability,colony forming efficiency and cell cycle distribution of HO8910/ TIZ-573 were increased,while the indexes of HO8910/pcDNA3.1-NC were decreased with statistical significant difference(P<0.05).There was no statistical significant difference in the invasion rate,migration rate and adhesion rate between 5 groups of cells(P>0.05).Conclusions:The expression of TIZ can inhibit the proliferation of epithelial ovarian cancer cells.展开更多
Objective To evaluate the efficacy of treatment options for patients with recurrent ovarian cancer.Methods From 1990 to 2000, 54 patients with recurrent ovarian cancer primarily treated in Peking Union Medical College...Objective To evaluate the efficacy of treatment options for patients with recurrent ovarian cancer.Methods From 1990 to 2000, 54 patients with recurrent ovarian cancer primarily treated in Peking Union Medical College Hospital were selected and reviewed.All the clinical data related to the recurrent tumor were collected.Two-side P values for differences in survival were calculated by the Cox regression model.Results The platinum-free interval >6 months and the surgery followed by salvage chemotherapy prolonged survival time of the patients with recurrent ovarian cancer (95% CI=0.153-0.987, P=0.047; 95% CI=1.611-10.914, P=0.003, respectively).The increased number of chemotherapy cycles (> 10 months) offered some benefit on the survival (95% CI=0.110-1.090, P=0.070).The initiation of treatment and chemotherapy regiments failed to demonstrate an improvement in survival.Conclusion The treatment options for patients with recurrent ovarian cancer depend on the platinum-free-interval of the patients.A strategy of secondary surgical cytoreduction followed by salvage chemotherapy is suggested for the patients with platinum-sensitive disease.展开更多
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 19...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.展开更多
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.Epithelia...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.展开更多
Objective Ovarian cancer(OC)is one of the most common and most lethal gynecological malignancies.OC has an age-dependent incidence and occurs more commonly in females older than 50 years old.Most OC patients are diagn...Objective Ovarian cancer(OC)is one of the most common and most lethal gynecological malignancies.OC has an age-dependent incidence and occurs more commonly in females older than 50 years old.Most OC patients are diagnosed at an advanced stage and have a poor prognosis.Germline mutations in the BRCA1 DNA repair associated gene(BRCA1)and the BRCA2 DNA repair associated gene(BRCA2)account for 20%–25%of epithelial ovarian cancer(EOC).BRCA1 germline mutations are more common in Chinese EOC patients.Methods This study reported a three-generation Han-Chinese family containing four EOC patients and a rectal adenocarcinoma patient.Whole-exome sequencing was performed on two EOC patients and an unaffected individual.Variant validation was also performed in all available members by Sanger sequencing.Results A heterozygous splice site variant,c.4358-2A>G in the BRCA1 gene,was identified.Bioinformatic analysis showed that the variant may change the splicing machinery.Conclusion The BRCA1 splice site variant,c.4358-2A>G was identified as the likely genetic cause for EOC,and may also be associated with the increased risk of rectal adenocarcinoma in the family.The findings were beneficial for genetic counseling,helpful for cancer prevention in other family members,and may facilitate therapy decision-making in the future to reduce cancer lethality.展开更多
Objective: The aim of this study was to compare the efficacies and safeties of the combination of docetaxel- carboplatin with the combination of non docetaxel-carboplatin as first-line chemotherapy for advanced epith...Objective: The aim of this study was to compare the efficacies and safeties of the combination of docetaxel- carboplatin with the combination of non docetaxel-carboplatin as first-line chemotherapy for advanced epithelial ovarian, pri- mary peritoneal or fallopian tube cancers. Methods: Relevant articles were identified from MEDLINE (1993-2010), EMBASE (1980-2010), MEDION, the Cochrane library, Science Citation Index Expanded databases, hand searching of reference lists from primary articles and reviews, conference abstracts and contact with experts in the field. The review included 5 relevant primary studies (1430 women). Data was extracted for study characteristics and quality. Bivariate random-effect model meta- analysis was used to estimate diagnostic accuracy of the various index tests. A quantitative meta-analysis was carried out by two reviewers based on the inclusion criteria from all available studies. Results: The frequency of the subgroup analysis of toxicity showed that toxicity action of combination of docetaxel-carboplatin was more severe than that of non docetaxel- carboplatin group (OR = 1.33, 95% CI = 1.13-1.56, P = 0.0005), whereas that of clinical responses was equivalent in com- parison combination of docetaxel-carboplatin with combination of paclitaxel-carboplatin or docetaxel-cisplatin (OR = 1.0, 95% CI = 0.87-1.16, P = 0.95). There were heterogeneity (X2 = 79.36, P 〈 0.00001) and inconsistency (83.6%) in toxicity analysis among the trials, while neither heterogeneity (x2 = 3.21, P = 0.99) nor inconsistency (F = 0%) in clinical responses among the trials. Conclusion: The safety of combination of docetaxel-carboplatin is less than that of combination of paclitaxel- carboplatin or docetaxel-cisplatin. However, the clinical responses of combination of docetaxel-carboplatin are comparable with combination of paclitaxel-carboplatin or docetaxel-cisplatin.展开更多
Epithelial ovarian cancer(EOC)is the most lethal gynaecological malignancy in the western world.The majority of women presenting with the disease are asymptomatic and it has been dubbed the“silent killer”.To date th...Epithelial ovarian cancer(EOC)is the most lethal gynaecological malignancy in the western world.The majority of women presenting with the disease are asymptomatic and it has been dubbed the“silent killer”.To date there is no effective minimally invasive method of stratifying those with the disease or screening for the disease in the general population.Recent molecular and pathological discoveries,along with the advancement of scientific technology,means there is a real possibility of having disease-specific liquid biopsies available within the clinical environment in the near future.In this review we discuss these discoveries,particularly in relation to the most common and aggressive form of EOC,and their role in making this possibility a reality.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.81572556 and 81402139).
文摘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.
文摘BACKGROUND Low grade serous carcinoma of the ovary(LGSOC)is a rare type of epithelial ovarian cancer with a low incidence rate.The origin of ovarian cancer has always been a hot topic in gynecological oncology research,and some scholars believe that the origin of ovarian malignant tumors is the fallopian tubes.Primary fallopian tube cancer is the lowest incidence of malignant tumors in the female reproductive system.There are only a few reports in the literature,but the mortality rate is very high.But in clinical practice,fallopian tube cancer is very common,but in most cases,it is classified as ovarian cancer.CASE SUMMARY We report a 54 years old postmenopausal woman who was hospitalized with a lower abdominal mass and underwent surgical treatment.The final pathological confirmation was low-grade serous carcinoma of the right ovary and low-grade serous carcinoma of the left fallopian tube.No special treatment was performed after the surgery,and the patient was instructed to undergo regular follow-up without any signs of disease progression.CONCLUSION The prognosis of LGSOC is relatively good,over 80%of patients still experience disease recurrence.
文摘The fatality rate of ovarian cancer (OC) is the highest, and the 5-year survival rate is only 50.8%. For more than 40 years, CA125 has been the most concerned and widely used biomarker of OC in clinical practice. In recent years, many researchers have proposed a reliable strategy of multiple markers combined with CA125 to screen OC to make up for the lack of accuracy of CA125, redefine the biochemical recurrence threshold of CA125, and use mathematical model scores to provide help for the feasibility of treatment and survival prognosis. To fully understand the role of CA125 in OC screening, initial treatment, and recurrence prediction, and summarize the limitations of CA125, this review has summarized the new progress of CA125 in the diagnosis and treatment of OC in recent years which can also provide a reference for clinicians.
文摘Despite significant effort and research funds, epithelial ovarian cancer remains a very deadly disease. There are no effective screening methods that discover early stage disease; the majority of patients are diagnosed with advanced disease. Treatment modalities consist primarily of radical debulking surgery followed by taxane and platinum-based chemotherapy. Newer therapies including limited targeted agents and intraperitoneal delivery of chemotherapeutic drugs have improved disease-free intervals, but failed to yield longlasting cures in most patients. Chemotherapeutic resistance, particularly in the recurrent setting, plagues the disease. Targeting the pathways and mechanisms behind the development of chemoresistance in ovarian cancer could lead to significant improvement in patient outcomes. In many malignancies, including blood and other solid tumors, there is a subgroup of tumor cells, separate from the bulk population, called cancer stem cells(CSCs). These CSCs are thought to be the cause of metastasis, recurrence and resistance. However, todate, ovarian CSCs have been difficult to identify, isolate, and target. It is felt by many investigators that finding a putative ovarian CSC and a chemotherapeutic agent to target it could be the key to a cure for this deadly disease. This review will focus on recent advances in this arena and discuss some of the controversies surrounding the concept.
基金supported by the Natural Science Foundation of China(No.30872750)the Natural Science Foundation of Beijing(No.7092108)
文摘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.
文摘Objectives: To compare the survival and perioperafive morbidity between primary debulking surgery (PDS) and neoadjuvant chemotherapy followed by interval debulking surgery (NAC/IDS) in treating patients with advanced epithelial ovarian cancer (EOC). Methods: We retrospectively reviewed 67 patients with stage IIIC or iV EOC treated at Peking University Cancer Hospital from January 2006 to June 2009. VVherein, 37 and 30 patients underwent PDS and NAC/ IDS, respectively. Results: No difference in overall survival (OS) or progression-free survival (PFS) was observed between NAC/IDS group and PDS group (OS: 41.2 vs. 39.1 months, P=0.23; PFS: 27.1 vs. 24.3 months, P=0.37). The optimal debulking rate was 60% in the NAC/IDS group, which was significantly higher than that in the PDS group (32.4%) (P=0.024). The NAC/IDS group had significantly less intraoperative estimated blood loss and transfusion, lower nasogastric intubation rate, and earlier ambulation and recovery of intestinal function than the PDS group (P〈0.05). Conclusions: NAC/IDS is less invasive than PDS, and offers the advantages regarding optimal cytoreduction rate, intraoperative blood loss, and postoperative recovery, without significantly impairing the survival compared with PDS in treating patients with stage IIIC or IV EOC. Therefore, NAC/IDS may be a valuable treatment alternative for EOC patients.
文摘Ovarian cancer is the leading cause of death in women with gynecological cancer. Most patients are diagnosed at an advanced stage and have a poor prognosis.Currently, surgical tumor debulking, followed by platinum- and taxane-based chemotherapy is the standard treatment for advanced ovarian cancer. However, these patients are at great risk of recurrence and emerging drug resistance. Therefore, novel treatment strategies are required to improve outcomes for women with advanced ovarian cancer. A variety of molecular targeted agents, the majority of which are monoclonal antibodies and small-molecule protein-kinase inhibitors, have been explored in the management of ovarian cancer. The targets of these agents include angiogenesis, the human epidermal growth factor receptor family, ubiquitinproteasome pathway, epigenetic modulators, poly(ADPribose) polymerase (PARP), and mammalian target of rapamycin (mTOR) signaling pathway, which are aberrant in tumor tissue. The antiangiogenic agent, bevacizumab, has been reported as the most effective targeted agent and should be included in the standard chemotherapeutic regimen for advanced ovarian cancer. PARP inhibitors, which are mainly used in breast and ovarian cancer susceptibility gene-mutated patients, and mTOR inhibitors are also attractive treatment strategies, either alone or combination with chemotherapy, for ovarian cancer. Understanding the tumor molecular biology and identification of predictive biomarkers are essential steps for selection of the best treatment strategies. This article reviews the molecular mechanisms of the most promising targeted agents that are under early phase clinical evaluation for ovarian cancer.
基金This work was supported by grants from the National Natural Science Foundation of China (No. 30225037, 30400538, 30471991,30570731);the 973 Program of China (No. 2006CB503909, 2004CB518603);the "111" Project, and the Natural Science Foundation of Jiangsu Province (No. BK2004082, BK2006714).
文摘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.
基金Supported by In part by Georgia Cancer Coalition Distinguished Cancer Scholar award,NIH-NCRR-RCMI,No.G-12-RR003034,No.U54 RR02613,and No.5P20RR11104NIHMD research endowment,No.2S21MD000101,and No.U54CA118638ING foundation grant to Rao VN
文摘Ovarian cancer is the second most common gyneco-logical cancer and the leading cause of death in the United States. In this article we review the diagnosis and current management of epithelial ovarian cancer which accounts for over 95 percent of the ovarian malignancies. We will present various theories about the potential origin of ovarian malignancies. We will discuss the genetic anomalies and syndromes that may cause ovarian cancers with emphasis on Breast cancer type 1/2 mutations. The pathology and pathogenesis of ovarian carcinoma will also be presented. Lastly, we provide a comprehensive overview of treatment strategies and staging of ovarian cancer, conclusions and future directions.
基金supported by Jiangsu Cancer Hospital (ZK201606ZK201610)
文摘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.
文摘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.
基金supported by the General Project of Provincial Natural Science Research of the Anhui Higher Education Institutions(Grant No. KJ2015B096by)
文摘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.
基金supported by Science and Technology Innovation of Foshan [Grant No. 1920001001153]。
文摘Objective The underlying mechanism of Ezrin in ovarian cancer(OVCA) is far from being understood.Therefore, this study aimed to assess the role of Ezrin in OVCA cells(SKOV3 and Ca OV3) and investigate the associated molecular mechanisms.Methods We performed Western blotting, reverse transcription-quantitative polymerase chain reaction, MTT, cell colony, cell wound healing, transwell migration and invasion, Rho A and Rac active pull down assays, and confocal immunofluorescence experiments to evaluate the functions and molecular mechanisms of Ezrin overexpression or knockdown in the proliferation and metastasis of OVCA cells.Results The ectopic expression of Ezrin significantly increased cell proliferation, invasiveness, and epithelial–mesenchymal transition(EMT) in OVCA cells. By contrast, the knockdown of endogenous Ezrin prevented OVCA cell proliferation, invasiveness, and EMT. Lastly, we observed that Ezrin can positively regulate the active forms of Rho A rather than Rac-1 in OVCA cells, thereby promoting robust stress fiber formation.Conclusion Our results indicated that Ezrin regulates OVCA cell proliferation and invasiveness by modulating EMT and induces actin stress fiber formation by regulating Rho-GTPase activity, which provides novel insights into the treatment of the OVCA.
基金supported by Soft Science Research Project in Hebei Province(12457612)
文摘Objective:To study the change of TIZ expression in epithelial ovarian cancer cells.Methods:HO8910 cells were transinfected with siRNA to inhibit the expression of TIZ.pcDNA3.1-TIZ vectors were combined to increase the TIZ expression level.The cell viabilily,colony forming efficiency and cycle distribution of HO8910,HO8910/NC,HO8910/pcDNA3.1-NC,HO8910/ TIZ-573 and HO8910/pcDNA3.l-TIZ were compared,and the invasion rate,migration rate and adhesion rate between 5 groups of cells were compared.Results:Compared with those of HO8910,HO8910/NC and HO8910/pcDNA3.1-NC,the cell viability,colony forming efficiency and cell cycle distribution of HO8910/ TIZ-573 were increased,while the indexes of HO8910/pcDNA3.1-NC were decreased with statistical significant difference(P<0.05).There was no statistical significant difference in the invasion rate,migration rate and adhesion rate between 5 groups of cells(P>0.05).Conclusions:The expression of TIZ can inhibit the proliferation of epithelial ovarian cancer cells.
文摘Objective To evaluate the efficacy of treatment options for patients with recurrent ovarian cancer.Methods From 1990 to 2000, 54 patients with recurrent ovarian cancer primarily treated in Peking Union Medical College Hospital were selected and reviewed.All the clinical data related to the recurrent tumor were collected.Two-side P values for differences in survival were calculated by the Cox regression model.Results The platinum-free interval >6 months and the surgery followed by salvage chemotherapy prolonged survival time of the patients with recurrent ovarian cancer (95% CI=0.153-0.987, P=0.047; 95% CI=1.611-10.914, P=0.003, respectively).The increased number of chemotherapy cycles (> 10 months) offered some benefit on the survival (95% CI=0.110-1.090, P=0.070).The initiation of treatment and chemotherapy regiments failed to demonstrate an improvement in survival.Conclusion The treatment options for patients with recurrent ovarian cancer depend on the platinum-free-interval of the patients.A strategy of secondary surgical cytoreduction followed by salvage chemotherapy is suggested for the patients with platinum-sensitive disease.
文摘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.
基金supported by grants from the National Science Foundation of China (No.30801340No.30901586No.30770913)
文摘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.
基金the National Natural Science Foundation of China(No.81800219 and No.81873686)Natural Science Foundation of Hunan Province(No.2019JJ50927,No.2020JJ3057 and No.2020JJ4830)the Lotus Scholars Program of Hunan Province,and the Wisdom Accumulation and Talent Cultivation Project of the Third Xiangya Hospital of Central South University(No.YX202109).
文摘Objective Ovarian cancer(OC)is one of the most common and most lethal gynecological malignancies.OC has an age-dependent incidence and occurs more commonly in females older than 50 years old.Most OC patients are diagnosed at an advanced stage and have a poor prognosis.Germline mutations in the BRCA1 DNA repair associated gene(BRCA1)and the BRCA2 DNA repair associated gene(BRCA2)account for 20%–25%of epithelial ovarian cancer(EOC).BRCA1 germline mutations are more common in Chinese EOC patients.Methods This study reported a three-generation Han-Chinese family containing four EOC patients and a rectal adenocarcinoma patient.Whole-exome sequencing was performed on two EOC patients and an unaffected individual.Variant validation was also performed in all available members by Sanger sequencing.Results A heterozygous splice site variant,c.4358-2A>G in the BRCA1 gene,was identified.Bioinformatic analysis showed that the variant may change the splicing machinery.Conclusion The BRCA1 splice site variant,c.4358-2A>G was identified as the likely genetic cause for EOC,and may also be associated with the increased risk of rectal adenocarcinoma in the family.The findings were beneficial for genetic counseling,helpful for cancer prevention in other family members,and may facilitate therapy decision-making in the future to reduce cancer lethality.
文摘Objective: The aim of this study was to compare the efficacies and safeties of the combination of docetaxel- carboplatin with the combination of non docetaxel-carboplatin as first-line chemotherapy for advanced epithelial ovarian, pri- mary peritoneal or fallopian tube cancers. Methods: Relevant articles were identified from MEDLINE (1993-2010), EMBASE (1980-2010), MEDION, the Cochrane library, Science Citation Index Expanded databases, hand searching of reference lists from primary articles and reviews, conference abstracts and contact with experts in the field. The review included 5 relevant primary studies (1430 women). Data was extracted for study characteristics and quality. Bivariate random-effect model meta- analysis was used to estimate diagnostic accuracy of the various index tests. A quantitative meta-analysis was carried out by two reviewers based on the inclusion criteria from all available studies. Results: The frequency of the subgroup analysis of toxicity showed that toxicity action of combination of docetaxel-carboplatin was more severe than that of non docetaxel- carboplatin group (OR = 1.33, 95% CI = 1.13-1.56, P = 0.0005), whereas that of clinical responses was equivalent in com- parison combination of docetaxel-carboplatin with combination of paclitaxel-carboplatin or docetaxel-cisplatin (OR = 1.0, 95% CI = 0.87-1.16, P = 0.95). There were heterogeneity (X2 = 79.36, P 〈 0.00001) and inconsistency (83.6%) in toxicity analysis among the trials, while neither heterogeneity (x2 = 3.21, P = 0.99) nor inconsistency (F = 0%) in clinical responses among the trials. Conclusion: The safety of combination of docetaxel-carboplatin is less than that of combination of paclitaxel- carboplatin or docetaxel-cisplatin. However, the clinical responses of combination of docetaxel-carboplatin are comparable with combination of paclitaxel-carboplatin or docetaxel-cisplatin.
文摘Epithelial ovarian cancer(EOC)is the most lethal gynaecological malignancy in the western world.The majority of women presenting with the disease are asymptomatic and it has been dubbed the“silent killer”.To date there is no effective minimally invasive method of stratifying those with the disease or screening for the disease in the general population.Recent molecular and pathological discoveries,along with the advancement of scientific technology,means there is a real possibility of having disease-specific liquid biopsies available within the clinical environment in the near future.In this review we discuss these discoveries,particularly in relation to the most common and aggressive form of EOC,and their role in making this possibility a reality.