Endometriosis is an estrogen-dependent inflammatory disease,defined by the presence of functional endometrial tissue outside of the uterine cavity.This disease is one of the main gynecological diseases,affecting aroun...Endometriosis is an estrogen-dependent inflammatory disease,defined by the presence of functional endometrial tissue outside of the uterine cavity.This disease is one of the main gynecological diseases,affecting around 10%-15%women and girls of reproductive age,being a common gynecologic disorder.Although endometriosis is a benign disease,it shares several characteristics with invasive cancer.Studies support that it has been linked with an increased chance of developing endometrial ovarian cancer,representing an earlier stage of neoplastic processes.This is particularly true for women with clear cell carcinoma,low-grade serous carcinoma and endometrioid.However,the carcinogenic pathways between both pathologies remain poorly understood.Current studies suggest a connection between endometriosis and endometriosis-associated ovarian cancers(EAOCs)via pathways associated with oxidative stress,inflammation,and hyperestrogenism.This article aims to review current data on the molecular events linked to the development of EAOCs from endometriosis,specifically focusing on the complex relationship between the immune response to endometriosis and cancer,including the molecular mechanisms and their ramifications.Examining recent developments in immunotherapy and their potential to boost the effectiveness of future treatments.展开更多
Endometriosis is the leading cause of morbidity among premenopausal women and the complex pathogenesis of this disease remains controversial despite extensive research. This disease represents one of the most common g...Endometriosis is the leading cause of morbidity among premenopausal women and the complex pathogenesis of this disease remains controversial despite extensive research. This disease represents one of the most common gynecological problems. It is generally believed that this disease is due primarily to retrograde menstruation or transplantation of shed endometrium. Based on overwhelming data, ovarian endometrioma is considered a neoplastic process, since most endometriosis-associated ovarian carcinoma occur in the presence of atypical ovarian endometriosis. A study comparing patients with typical epithelial ovarian cancer with endometriosis-associated ovarian cancer demonstrated that the patients with the latter disease strongly differ in both biological and histological characteristics. The prevelance of this disease is not completely established, but approximately 15 percent of women suffer from this disease. In addition, we know about the possible links between endometriosis and cancer for almost 100 years. Despite clear evidence revealing that endometriosis increases ovariancancer risks, it is possible that it may not affect disease progression after the appearance of ovarian cancer. However, despite clear evidence revealing that endometriosis increases ovarian cancer risk, our knowledge of the risk factors is far from established. In our review, we focused on the most recent approaches including possible biomarkers and genetic approaches.展开更多
Introduction: It has been suggested the relationship between infertility treatment and ovarian cancer. Furthermore, endometriosis that is one of the causes of the infertility tends to develop into endometrioid adenoca...Introduction: It has been suggested the relationship between infertility treatment and ovarian cancer. Furthermore, endometriosis that is one of the causes of the infertility tends to develop into endometrioid adenocarcinoma and clear cell carcinoma in many studies. Case: A 38-year-old woman underwent laparoscopic enucleation of bilateral ovarian endometrial cysts at 29 and 33 years old. She then received 11 sessions of artificial insemination and 7 cycles of ovarian stimulation, egg collection,?in vitro?fertilization, and embryo transfer at multiple medical institutions before conceiving and giving birth to her first child. After naturally conceiving her second child, she presented at our hospital for pregnancy/delivery management with a right ovarian tumor. She underwent abdominal right adnexectomy for a mucinous cystic tumor of borderline malignancy at 36 years old (17 weeks of pregnancy with the second child). After vaginal delivery at 38 weeks, a 1-month postpartum checkup revealed a left adnexal mass and ascites. Further workup led to a diagnosis of left ovarian cancer. The cancer was diagnosed by ovarian biopsy as unresectable stage-IIIc endometrioid carcinoma. Despite chemotherapy, the patient developed liver metastasis during treatment and died due to worsened general condition 9 months after childbirth. In addition to ovarian endometrial cyst, repeated cycles of injury and repair of the ovarian surface epithelium are also suggested to mediate the development of epithelial ovarian cancer. Conclusion: Evaluation of long-term outcome and follow-up of patients who have undergone fertility treatment should be addressed.展开更多
Ovarian cancer is the fifth lethal gynecologic malignancy. Metastasis-associated gene 1 (MTA1) is overexpressed in many malignant tumors with high metastatic potential. This study investigated whether down-regulation ...Ovarian cancer is the fifth lethal gynecologic malignancy. Metastasis-associated gene 1 (MTA1) is overexpressed in many malignant tumors with high metastatic potential. This study investigated whether down-regulation of MTA1 expression by RNAi in A2780 ovarian cancer cells could affect proliferation, anoikis, migration, invasion and adhesion of the cells and to research the potential for MTA1 gene therapy of ovarian cancer. After transfection with effective Mta1 gene siRNA, the effects on proliferation, anoikis, migration, invasion and adhesion of A2780 cells were tested by MTT assay, flow cytometry, wound-healing assay, Transwell assay and adhesion assay. Expression levels of PTEN, beta 1 integrin, MMP-9, phosphor-AKT (Ser473), and total AKT activity were evaluated in control and transfected cells. The results showed that inhibition of MTA1 mediated by Mta1-siRNA transfection decreased the cell invasion, migration and adhesion, and induced the increased cell anoikis, but no significant difference was found in proliferation of A2780 cancer cells. In addition, beta 1 integrin, MMP-9, and phosphor-AKT protein levels were significantly down-regulated, while PTEN was significantly up-regulated. These results demonstrated that MTA1 played an important role in the cell metastasis in ovarian cancer. MTA1 could serve as another novel potential therapeutic target in ovarian cancer.展开更多
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 h...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.展开更多
Objective To explore the expression and clinicopathological significance of RASSF1A and WT1 in recurrent epithelial ovarian cancer.Methods Sixty-three cases of patients with pathologically confirmed epithelial ovarian...Objective To explore the expression and clinicopathological significance of RASSF1A and WT1 in recurrent epithelial ovarian cancer.Methods Sixty-three cases of patients with pathologically confirmed epithelial ovarian cancer were collected in the department of Gynaecology and Obsterics of the North China University of Technology from January 2013 to December 2018.The expression of RASSF1A and WT1 were measured by IHC staining.The relation of these proteins with ovarian cancer was also analyzed.Results Compared with non-recurrent group(46.4%),the positive expression rate of RASSF1A was 17.1%in recurrent group.The positive expression rate of WT1 was 74.3%and higher than the rate of 42.8%in non-recurrent group.The reducing expression of RASSF1A was related to clinical stage,differentiation,and with ascites(P<0.05).The increasing expression of WT1 was related to pathological type,clinical stage,histological differentiation,with ascites,and lymph node metastasis(P<0.05).Conclusion Low expression of RASSF1A and high expression of WT1 may be related to recurrent epithelial ovarian cancer.展开更多
目的探索乳腺癌/卵巢癌易感基因1相关蛋白1(breast/ovarian cancer susceptibility gene 1 associated protein 1,BAP1)对人源恶性胶质瘤发生、发展的作用与BAP1作为恶性胶质瘤临床诊断标志物的可行性。方法基于基因表达综合数据库(gene...目的探索乳腺癌/卵巢癌易感基因1相关蛋白1(breast/ovarian cancer susceptibility gene 1 associated protein 1,BAP1)对人源恶性胶质瘤发生、发展的作用与BAP1作为恶性胶质瘤临床诊断标志物的可行性。方法基于基因表达综合数据库(gene expression omnibus,GEO)的子数据集GSE4290,GSE90598,分析BAP1在正常组织及胶质瘤组织中的差异性表达情况;受试者工作特征(receiver operating characteristic,ROC)曲线分析BAP1对恶性胶质瘤的早期诊断价值;选取自主收集的非配对28例恶性胶质瘤患者的原发灶组织、5例颅脑外伤患者内减压术切除的非瘤脑组织,采用实时荧光定量PCR(quantitative real-time polymerase chain reaction,qRT-PCR)检测BAP1的表达水平;利用靶向BAP1的特异性小干扰RNAs(small interfering RNAs,siRNAs)瞬时转染U251细胞系,进一步检测其干涉效率;基于流式细胞仪分析BAP1下调的U251细胞系,其细胞周期、凋亡的变化情况。结果生物信息学结果显示,BAP1在恶性胶质瘤组织中的表达水平均低于正常脑组织(GSE4290:1209±18.49 vs 1476±53.90;GSE90598:5.19±0.10 vs 5.65±0.21),差异具有统计学意义(t=5.115,2.267,均P<0.05)。ROC曲线显示,BAP1可高效区分恶性胶质瘤组织与正常脑组织(GSE4290:AUC=0.78;GSE90598:AUC=0.75,均P<0.05)。临床标本结果显示,BAP1在恶性胶质瘤原发灶组织中的表达水平显著低于非瘤脑组织(0.27±0.04 vs 1.06±0.07),差异具有统计学意义(t=10.22,P<0.001)。在U251细胞系中下调BAP1的表达,其细胞周期中S期细胞比例明显增多,由17.59%分别增至27.21%(siBAP1-1)和25.79%(siBAP1-2),差异具有统计学意义(t=6.576,6.642,均P<0.01),而细胞凋亡水平则有所下降,由10.17%分别降至2.70%(siBAP-1)和3.00%(siBAP-2),差异具有统计学意义(t=10.31,9.428,均P<0.01)。结论组蛋白H2A去泛素化酶BAP1能够通过抑制恶性胶质瘤细胞周期快速进展并促进其凋亡,进而发挥肿瘤抑癌基因的功能,可作为潜在的恶性胶质瘤临床诊断标志物。展开更多
Objective:To study the prevalence and associated factors of recurrent ovarian endometrioma after ovarian cystectomy.Methods:This retrospective study analyzed 303 patients who underwent cystectomy for ovarian endometri...Objective:To study the prevalence and associated factors of recurrent ovarian endometrioma after ovarian cystectomy.Methods:This retrospective study analyzed 303 patients who underwent cystectomy for ovarian endometrioma and had at least a 2-year follow-up at Srinagarind Hospital from January 2013 to December 2018.The patients were divided into the recurrent and nonrecurrent groups according to the findings from postoperative transvaginal ultrasonography 6 months after undergoing surgery.Nineteen factors were collected for risk evaluation.The prevalence of recurrent ovarian endometrioma and its 95%confident interval(CI)were calculated.Univariate and multivariable logistic regression analyses were performed to determine the association between factors and recurrence.Results:Recurrent ovarian endometrioma occurred in 33%(95%CI 27.7%-38.3%)patients.The median duration of followup was 36 months.during the median follow-up period of 36 months.Preoperative history of parity,preoperative infertility history,endometriosis surgery,moderate to severe dysmenorrhea,dyspareunia,intraoperative stage 4 according to revised American Society for Reproductive Medicine classification,presence of adenomyosis,and postoperative pain relief were associated factors based on univariate analysis.In contrast,infertility[odds ratio(OR)2.22,95%CI 1.14-4.33],moderate to severe dysmenorrhea(OR 2.13,95%CI 1.09-4.15),and postoperative pelvic pain relief(OR 0.22,95%CI 0.12-0.42)were independently associated factors based on multivariable logistic regression analysis.Conclusions:In our setting,preoperative infertility history and moderate to severe dysmenorrhea were associated with a higher recurrent ovarian endometrioma risk.In contrast,postoperative pain relief was significantly associated with lower recurrence risk.展开更多
文摘Endometriosis is an estrogen-dependent inflammatory disease,defined by the presence of functional endometrial tissue outside of the uterine cavity.This disease is one of the main gynecological diseases,affecting around 10%-15%women and girls of reproductive age,being a common gynecologic disorder.Although endometriosis is a benign disease,it shares several characteristics with invasive cancer.Studies support that it has been linked with an increased chance of developing endometrial ovarian cancer,representing an earlier stage of neoplastic processes.This is particularly true for women with clear cell carcinoma,low-grade serous carcinoma and endometrioid.However,the carcinogenic pathways between both pathologies remain poorly understood.Current studies suggest a connection between endometriosis and endometriosis-associated ovarian cancers(EAOCs)via pathways associated with oxidative stress,inflammation,and hyperestrogenism.This article aims to review current data on the molecular events linked to the development of EAOCs from endometriosis,specifically focusing on the complex relationship between the immune response to endometriosis and cancer,including the molecular mechanisms and their ramifications.Examining recent developments in immunotherapy and their potential to boost the effectiveness of future treatments.
文摘Endometriosis is the leading cause of morbidity among premenopausal women and the complex pathogenesis of this disease remains controversial despite extensive research. This disease represents one of the most common gynecological problems. It is generally believed that this disease is due primarily to retrograde menstruation or transplantation of shed endometrium. Based on overwhelming data, ovarian endometrioma is considered a neoplastic process, since most endometriosis-associated ovarian carcinoma occur in the presence of atypical ovarian endometriosis. A study comparing patients with typical epithelial ovarian cancer with endometriosis-associated ovarian cancer demonstrated that the patients with the latter disease strongly differ in both biological and histological characteristics. The prevelance of this disease is not completely established, but approximately 15 percent of women suffer from this disease. In addition, we know about the possible links between endometriosis and cancer for almost 100 years. Despite clear evidence revealing that endometriosis increases ovariancancer risks, it is possible that it may not affect disease progression after the appearance of ovarian cancer. However, despite clear evidence revealing that endometriosis increases ovarian cancer risk, our knowledge of the risk factors is far from established. In our review, we focused on the most recent approaches including possible biomarkers and genetic approaches.
文摘Introduction: It has been suggested the relationship between infertility treatment and ovarian cancer. Furthermore, endometriosis that is one of the causes of the infertility tends to develop into endometrioid adenocarcinoma and clear cell carcinoma in many studies. Case: A 38-year-old woman underwent laparoscopic enucleation of bilateral ovarian endometrial cysts at 29 and 33 years old. She then received 11 sessions of artificial insemination and 7 cycles of ovarian stimulation, egg collection,?in vitro?fertilization, and embryo transfer at multiple medical institutions before conceiving and giving birth to her first child. After naturally conceiving her second child, she presented at our hospital for pregnancy/delivery management with a right ovarian tumor. She underwent abdominal right adnexectomy for a mucinous cystic tumor of borderline malignancy at 36 years old (17 weeks of pregnancy with the second child). After vaginal delivery at 38 weeks, a 1-month postpartum checkup revealed a left adnexal mass and ascites. Further workup led to a diagnosis of left ovarian cancer. The cancer was diagnosed by ovarian biopsy as unresectable stage-IIIc endometrioid carcinoma. Despite chemotherapy, the patient developed liver metastasis during treatment and died due to worsened general condition 9 months after childbirth. In addition to ovarian endometrial cyst, repeated cycles of injury and repair of the ovarian surface epithelium are also suggested to mediate the development of epithelial ovarian cancer. Conclusion: Evaluation of long-term outcome and follow-up of patients who have undergone fertility treatment should be addressed.
基金supported by the youth innovation fundation of the First Affiliated Hospital of Zhengzhou University
文摘Ovarian cancer is the fifth lethal gynecologic malignancy. Metastasis-associated gene 1 (MTA1) is overexpressed in many malignant tumors with high metastatic potential. This study investigated whether down-regulation of MTA1 expression by RNAi in A2780 ovarian cancer cells could affect proliferation, anoikis, migration, invasion and adhesion of the cells and to research the potential for MTA1 gene therapy of ovarian cancer. After transfection with effective Mta1 gene siRNA, the effects on proliferation, anoikis, migration, invasion and adhesion of A2780 cells were tested by MTT assay, flow cytometry, wound-healing assay, Transwell assay and adhesion assay. Expression levels of PTEN, beta 1 integrin, MMP-9, phosphor-AKT (Ser473), and total AKT activity were evaluated in control and transfected cells. The results showed that inhibition of MTA1 mediated by Mta1-siRNA transfection decreased the cell invasion, migration and adhesion, and induced the increased cell anoikis, but no significant difference was found in proliferation of A2780 cancer cells. In addition, beta 1 integrin, MMP-9, and phosphor-AKT protein levels were significantly down-regulated, while PTEN was significantly up-regulated. These results demonstrated that MTA1 played an important role in the cell metastasis in ovarian cancer. MTA1 could serve as another novel potential therapeutic target in ovarian cancer.
基金Supported by a grant from the Health Department of Hainan Province(No.QW2013-040)
文摘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.
文摘Objective To explore the expression and clinicopathological significance of RASSF1A and WT1 in recurrent epithelial ovarian cancer.Methods Sixty-three cases of patients with pathologically confirmed epithelial ovarian cancer were collected in the department of Gynaecology and Obsterics of the North China University of Technology from January 2013 to December 2018.The expression of RASSF1A and WT1 were measured by IHC staining.The relation of these proteins with ovarian cancer was also analyzed.Results Compared with non-recurrent group(46.4%),the positive expression rate of RASSF1A was 17.1%in recurrent group.The positive expression rate of WT1 was 74.3%and higher than the rate of 42.8%in non-recurrent group.The reducing expression of RASSF1A was related to clinical stage,differentiation,and with ascites(P<0.05).The increasing expression of WT1 was related to pathological type,clinical stage,histological differentiation,with ascites,and lymph node metastasis(P<0.05).Conclusion Low expression of RASSF1A and high expression of WT1 may be related to recurrent epithelial ovarian cancer.
文摘目的探索乳腺癌/卵巢癌易感基因1相关蛋白1(breast/ovarian cancer susceptibility gene 1 associated protein 1,BAP1)对人源恶性胶质瘤发生、发展的作用与BAP1作为恶性胶质瘤临床诊断标志物的可行性。方法基于基因表达综合数据库(gene expression omnibus,GEO)的子数据集GSE4290,GSE90598,分析BAP1在正常组织及胶质瘤组织中的差异性表达情况;受试者工作特征(receiver operating characteristic,ROC)曲线分析BAP1对恶性胶质瘤的早期诊断价值;选取自主收集的非配对28例恶性胶质瘤患者的原发灶组织、5例颅脑外伤患者内减压术切除的非瘤脑组织,采用实时荧光定量PCR(quantitative real-time polymerase chain reaction,qRT-PCR)检测BAP1的表达水平;利用靶向BAP1的特异性小干扰RNAs(small interfering RNAs,siRNAs)瞬时转染U251细胞系,进一步检测其干涉效率;基于流式细胞仪分析BAP1下调的U251细胞系,其细胞周期、凋亡的变化情况。结果生物信息学结果显示,BAP1在恶性胶质瘤组织中的表达水平均低于正常脑组织(GSE4290:1209±18.49 vs 1476±53.90;GSE90598:5.19±0.10 vs 5.65±0.21),差异具有统计学意义(t=5.115,2.267,均P<0.05)。ROC曲线显示,BAP1可高效区分恶性胶质瘤组织与正常脑组织(GSE4290:AUC=0.78;GSE90598:AUC=0.75,均P<0.05)。临床标本结果显示,BAP1在恶性胶质瘤原发灶组织中的表达水平显著低于非瘤脑组织(0.27±0.04 vs 1.06±0.07),差异具有统计学意义(t=10.22,P<0.001)。在U251细胞系中下调BAP1的表达,其细胞周期中S期细胞比例明显增多,由17.59%分别增至27.21%(siBAP1-1)和25.79%(siBAP1-2),差异具有统计学意义(t=6.576,6.642,均P<0.01),而细胞凋亡水平则有所下降,由10.17%分别降至2.70%(siBAP-1)和3.00%(siBAP-2),差异具有统计学意义(t=10.31,9.428,均P<0.01)。结论组蛋白H2A去泛素化酶BAP1能够通过抑制恶性胶质瘤细胞周期快速进展并促进其凋亡,进而发挥肿瘤抑癌基因的功能,可作为潜在的恶性胶质瘤临床诊断标志物。
文摘Objective:To study the prevalence and associated factors of recurrent ovarian endometrioma after ovarian cystectomy.Methods:This retrospective study analyzed 303 patients who underwent cystectomy for ovarian endometrioma and had at least a 2-year follow-up at Srinagarind Hospital from January 2013 to December 2018.The patients were divided into the recurrent and nonrecurrent groups according to the findings from postoperative transvaginal ultrasonography 6 months after undergoing surgery.Nineteen factors were collected for risk evaluation.The prevalence of recurrent ovarian endometrioma and its 95%confident interval(CI)were calculated.Univariate and multivariable logistic regression analyses were performed to determine the association between factors and recurrence.Results:Recurrent ovarian endometrioma occurred in 33%(95%CI 27.7%-38.3%)patients.The median duration of followup was 36 months.during the median follow-up period of 36 months.Preoperative history of parity,preoperative infertility history,endometriosis surgery,moderate to severe dysmenorrhea,dyspareunia,intraoperative stage 4 according to revised American Society for Reproductive Medicine classification,presence of adenomyosis,and postoperative pain relief were associated factors based on univariate analysis.In contrast,infertility[odds ratio(OR)2.22,95%CI 1.14-4.33],moderate to severe dysmenorrhea(OR 2.13,95%CI 1.09-4.15),and postoperative pelvic pain relief(OR 0.22,95%CI 0.12-0.42)were independently associated factors based on multivariable logistic regression analysis.Conclusions:In our setting,preoperative infertility history and moderate to severe dysmenorrhea were associated with a higher recurrent ovarian endometrioma risk.In contrast,postoperative pain relief was significantly associated with lower recurrence risk.
