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Sample records for advanced epithelial ovarian

  1. Surgery for advanced epithelial ovarian cancer.

    Science.gov (United States)

    Hacker, Neville F; Rao, Archana

    2016-10-20

    Cytoreductive surgery for patients with advanced epithelial ovarian cancer has been practised since the pioneering work of Tom Griffiths in 1975. Further research has demonstrated the prognostic significance of the extent of metastatic disease pre-operatively, and of complete cytoreduction post-operatively. Patients with advanced epithelial ovarian cancer should be referred to high volume cancer units, and managed by multidisciplinary teams. The role of thoracoscopy and resection of intrathoracic disease is presently investigational. In recent years, there has been increasing use of neoadjuvant chemotherapy and interval cytoreductive surgery in patients with poor performance status, which is usually due to large volume ascites and/or large pleural effusions. Neoadjuvant chemotherapy reduces the post-operative morbidity, but if the tumour responds well to the chemotherapy, the inflammatory response makes the surgery more difficult. Post-operative morbidity is generally tolerable, but increases in older patients, and in those having multiple, aggressive surgical procedures, such as bowel resection or diaphragmatic stripping. Primary cytoreductive surgery should be regarded as the gold standard for most patients until a test is developed which would allow the prediction of platinum resistance pre-operatively.

  2. Optimal cytoreduction for advanced epithelial ovarian cancer

    Directory of Open Access Journals (Sweden)

    N. G. Kormosh

    2010-01-01

    Full Text Available This article is review of literature on role of surgery in the initial management of advanced stage ovarian cancer, focusing on the definition of optimum surgical cytoreduction, assessment of resectability, estimation of the risk of postoperative complications. Analyze of published scien- tific data suggest that removal of all evidence of macroscopic disease should be the goal of primary or interval cytoreductive surgery.

  3. Study of consolidation chemotherapy in advanced epithelial ovarian carcinoma

    Institute of Scientific and Technical Information of China (English)

    Cheng Ning-hai; Huang Hui-fang; Pan Lin-ya; Shen Keng; Wu Ming; Yang Jia-xin

    2007-01-01

    Objective: A prospective randomized study was designed to evaluate the role of consolidation chemotherapy in advanced epithelial ovarian carcinoma.Methods: 50 patients with advanced epithelial ovarian carcinoma treated in our hospital during the period from March 2000 to October 2005 were enrolled in this study.All patients had achieved clinical complete remission by means of standard treatments, and were randomly divided into consolidation chemotherapy group and control group.Relapse rate, and disease-free survival(DFS) time were analyzed in both groups.Results: 24 patients were assigned in consolidation chemotherapy group, and 26 patients in control group.Tumor relapse interval in consolidation group was (26.5±7.4) months, vs.(16.8±7.0) months in control group respectively, P=0.001.Time to relapse(TTR) in consolidation group was (19.2±6.8) months, vs.(10.0±6.9)months in control group, P=0.002.Analysis of DFS time and overall survival time, Log Rank test:P=0.042 and P= 0.062, respectively.Conclusions: Consolidation chemotherapy could be the relevant factor that postpones tumor relapse interval and prolongs DFS time in advanced epithelial ovarian carcinoma patients who had achived chlinical complete remission.But so far the statistic result of our clinical study is beyond the conclusion that consolidation chemotherapy can decrease relapse rate or increase survival rate.Muhicenter randomized clinical trial should be performed to confirm the role of consolidation chemotherapy in advanced epithelial ovarian carcinoma.

  4. Primary Surgery or Interval Debulking for Advanced Epithelial Ovarian Cancer

    DEFF Research Database (Denmark)

    Markauskas, Algirdas; Mogensen, Ole; dePont Christensen, René

    2014-01-01

    OBJECTIVE: The aim of the present study was to investigate the surgical complexity, the postoperative morbidity, and the survival of the women after primary debulking surgery (PDS) and neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS) for advanced epithelial ovarian cancer....... MATERIALS AND METHODS: We consecutively included all patients who underwent debulking surgery at our institution between January 2007 and December 2012 for stages IIIc and IV of epithelial ovarian cancer. RESULTS: Of the 332 patients included, 165 (49.7%) underwent PDS, and 167 (50.3%) had NACT......-IDS have greater than 1 cm of tumor tissue left after the operation. These women probably have no survival benefit from the operation, and future studies should focus on how to select these women preoperatively....

  5. Neoadjuvant intraarterial chemotherapy and embolization in treatment of advanced ovarian epithelial carcinoma

    Institute of Scientific and Technical Information of China (English)

    刘恩令; 糜若然

    2004-01-01

    Background The purpose of the study was to evaluate the role of neoadjuvant chemotherapy and embolization via the anterior branches of the bilateral internal iliac arteries in treating patients with advanced ovarian epithelial carcinoma.Methods Forty-two patients with advanced ovarian epithelial carcinoma (study group) were treated via the anterior branches of the bilateral internal iliac arteries after cytoreductive surgery and 7 courses of adjuvant platinum-based combination chemotherapy. Primary cytoreductive surgery was performed in 43 patients with advanced ovarian epithelial carcinoma (control group), and then followed by 8 courses of adjuvant platinum-based combination chemotherapy. The rate of optimal cytoreductive surgery, survival rate, blood loss during operation and operative time were investigated in the two groups. Statistical significance was asessed using Student's t test, the Chi-squre test and the log-rank test. Results In the study group, the rate of optimum debulking after platinum-based chemotherapy and embolization via the anterior branches of the bilateral internal iliac arteries was 71.43%(30/42) (χ2=10.06, P0.05).Conclusions Neoadjuvant platinum-based combination chemotherapy and embolization via the anterior branches of the bilateral internal iliac arteries is an alternative treatment for patients with advanced ovarian epithelial carcinoma, in whom the chance of optimal cytoreductive surgery is low. The treatment can reduce blood loss, decrease operative time, and increase the rate of optimal cytoreductive surgery; but the median survival can't be improved significantly.

  6. Can primary optimal cytoreduction be predicted in advanced epithelial ovarian cancer preoperatively?

    Directory of Open Access Journals (Sweden)

    Behtash Nadereh

    2010-02-01

    Full Text Available Abstract Introduction Prediction of optimal cytoreduction in patients with advanced epithelial ovarian caner preoperatively. Methods Patients with advanced epithelial ovarian cancer who underwent surgery for the first time from Jan. to June 2008 at gynecologic oncology ward of TUMS (Tehran University of Medical Sciences were eligible for this study. The possibility of predicting primary optimal cytoreduction considering multiple variables was evaluated. Variables were peritoneal carcinomatosis, serum CA125, ascites, pleural effusion, physical status and imaging findings. Univariate comparisons of patients underwent suboptimal cytoreduction carried out using Fisher's exact test for each of the potential predictors. The wilcoxon rank sum test was used to compare variables between patients with optimal versus suboptimal cytoreduction. Results 41 patients met study inclusion criteria. Statistically significant association was noted between peritoneal carcinomatosis and suboptimal cytoreduction. There were no statistically significant differences between physical status, pleural effusion, imaging findings, serum CA125 and ascites of individuals with optimal cytoreduction compared to those with suboptimal cytoreduction. Conclusions Because of small populations in our study the results are not reproducible in alternate populations. Only the patient who is most unlikely to undergo optimal cytoreduction should be offered neoadjuvant chemotherapy, unless her medical condition renders her unsuitable for primary surgery.

  7. Intraoperative radiotherapy electron boost in advanced and recurrent epithelial ovarian carcinoma: a retrospective study

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    Zhang Long

    2011-10-01

    Full Text Available Abstract Background Relapses of epithelial ovarian carcinoma (EOC have a poor prognosis and are almost always fatal. The aim of this study was to evaluate the clinical outcome and toxicity of intraoperative electron beam radiation therapy (IOERT in advanced and recurrent EOC. Methods Forty-five women with EOC were treated with IOERT. Twenty-five patients had primary disease (PD without distant metastasis at IOERT, and 20 patients had an isolated local recurrence (ILR after surgery. All 45 patients in this series underwent optimal cytoreductive (≤ 1 cm surgery. The whole pelvic (WP radiotherapy was intraoperatively delivered using 12 Mev electron beam; 43 patients received 18-20 Gy and two patients received 10 Gy. Thirty-three patients received postoperateive intraperitoneal (IP chemotherapy, while seven patients received intravenous (IV chemotherapy. Five patients refused concurrent chemotherapy. Overall survival (OS rates were analyzed using the Kaplan-Meier method. Results Tumor recurrence and metastasis were observed in 16 patients (35.6%. Of those, 14 patients (31.1% relapsed and two patients (4.4% had distant metastasis alone. Eight of 25 (32% local failures were observed in the PD group, as compared to 6/20 (30% in the ILR group (P = 0.885. Actuarial local control at five year follow-up was 31/45 (68.9%. Seventeen of the total 45 (37.8% patients died. Nine of 25 (36% in the PD group died, as compared to 8 of 20 (40% in the ILR group. The 5-year OS and disease-free survival (DFS rates were 28/45 (62.2% and 25/45 (55.6%, respectively. In the PD group, the 5-year OS and DFS rates were 16/25 (64% and 14/25 (56% (P > 0.05, vs. the ILR group at 12/20 and 11/20, respectively. The OS and DFS in the IOERT plus IP group were 25/33 (75.8% and 23/33 (69.7%, respectively, which were superior to the rates achieved with IOERT plus IV chemotherapy (P Conclusions IOERT may be feasible and effective as a boosting technique for advanced and recurrent

  8. Management of brain metastasis in a patient with advanced epithelial ovarian carcinoma by gamma-knife radiosurgery

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    Nikolaou Marinos

    2015-01-01

    Full Text Available Introduction. Brain metastases from epithelial ovarian cancer (EOC are rare events. We present a rare case of single ovarian cancer metastasis to the brain treated with gamma-knife radiosurgery (GKRS. Case Outline. A 65-year-old woman with advanced EOC presented with severe neurologic symptoms. A single brain metastasis of 3.2 cm with surrounding edema in the left parietal lobe was detected by brain magnetic resonance imaging (MRI scan during the work-up. The decision to perform GKRS was due to a surgical inaccessibility of intracranial lesion. Twelve weeks after the procedure, the MRI scan showed reduction in the diameter of brain metastasis and surrounding edema and the patient returned to good mental and motor performance. The patient survived for 22 months following treatment and died from a progressive intra-abdominal disease. Prognosis of ovarian cancer patients with brain metastases is generally poor regardless of treatment. Conclusion. Our case shows that GKRS as primary treatment modality for the control of ovarian cancer metastases to the brain was effective and can be considered as a treatment of choice if international selection criteria are followed.

  9. Prognostic factors in advanced epithelial ovarian cancer. (Gruppo Interregionale Cooperativo di Oncologia Ginecologica (GICOG)).

    Science.gov (United States)

    Marsoni, S; Torri, V; Valsecchi, M G; Belloni, C; Bianchi, U; Bolis, G; Bonazzi, C; Colombo, N; Epis, A; Favalli, G

    1990-09-01

    The data on 914 patients enrolled in four randomised trials in advanced ovarian cancer, consecutively conducted by the same cooperative group between 1978 and 1986, were analysed with the aims of: (1) determining the impact of selected prognostic variables on survival; (2) finding, from the interaction of favourable prognostic factors and treatment, an approximate estimate of the magnitude of the survival advantage associated with the use of platinum-based combination chemotherapy. The overall 3-year survival in this series of patients is twice that reported historically (22%; 95% CL 18.7-25.4). The proportional hazard regression model was used to perform the analysis on survival. Residual tumour size, age, FIGO stage and cell type were all independent determinants of survival. Differences in survival from the various prognostic groups were impressive with 5-year survival rates ranging from 7 to 62%. However, these differences were not qualitative (i.e. the kinetics of survival were similar for the best and the worst groups) suggesting that current prognostic factors are of little use for selecting 'biologically' different sub-populations. Platinum-based regimens were associated to an overall prolonged median survival, but this benefit was not observable in the subgroup with most favourable prognosis (less than 2 cm residual tumour size). The implications of these observations for clinical research and ovarian cancer patients care are discussed.

  10. Cost-effectiveness of early-initiated treatment for advanced-stage epithelial ovarian cancer patients: a modeling study

    NARCIS (Netherlands)

    Hoyer, T.; Bekkers, R.L.; Gooszen, H.G.; Massuger, L.F.A.G.; Rovers, M.M.; Grutters, J.P.C.

    2014-01-01

    OBJECTIVE: Between diagnosis and primary treatment of patients with epithelial ovarian cancer (EOC), gaps of several weeks exist. Reducing these time intervals may benefit the patient and may lead to a reduction of costs. We explored the cost-effectiveness of early-initiated treatment of patients wi

  11. Management of recurrent epithelial ovarian cancer

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    Moreno-Eutimio, Mario Adan; Acosta-Altamirano, Gustavo; Vargas-Aguilar, Víctor Manuel

    2014-01-01

    Epithelial ovarian cancer is the fifth most common cancer in women. It is usually diagnosed at an advanced stage and is the leading cause of death from gynecologic cancers in women. The overall survival rate at five years is 50% and its treatment is still poor. We need new treatments for patients with recurrent ovarian cancer who are incurable with current management. We review the effectiveness of new biological agents and morbidity and mortality of cytoreductive surgery. Since the hyperthermic increases the effectiveness of chemotherapy and the chance of survival, hyperthermic intraperitoneal chemotherapy has been proven to be a promising option, however it still requires further study to be the standard treatment. PMID:25207212

  12. Lack of relationship between TIMP-1 tumour cell immunoreactivity, treatment efficacy and prognosis in patients with advanced epithelial ovarian cancer

    DEFF Research Database (Denmark)

    Steffensen, Karina Dahl; Waldstrøm, Marianne; Christensen, Rikke Kølby

    2010-01-01

    BACKGROUND: Tissue inhibitor of metalloproteinase 1 (TIMP-1) is a natural inhibitor of the matrix metalloproteinases (MMPs) which are proteolytic enzymes involved in degradation of extracellular matrix thereby favoring tumour cell invasion and metastasis. TIMP-1 activity in tumour tissue may ther...... immunoreactivity in tumour tissue from patients with primary epithelial ovarian cancer did not correlate with patient survival or response to combination platinum/cyclophosphamide therapy.......BACKGROUND: Tissue inhibitor of metalloproteinase 1 (TIMP-1) is a natural inhibitor of the matrix metalloproteinases (MMPs) which are proteolytic enzymes involved in degradation of extracellular matrix thereby favoring tumour cell invasion and metastasis. TIMP-1 activity in tumour tissue may...... therefore play an essential role in the progression of a malignant tumour.The primary aim of the present study was to evaluate TIMP-1 protein immunoreactivity in tissue from primary ovarian cancer patients and associate these findings with the course of the disease including response to treatment...

  13. Dock180 expression in epithelial ovarian tumors

    Institute of Scientific and Technical Information of China (English)

    Hui Wang; Huhua Ling; Zhenwei Yao

    2012-01-01

    Objective: The aim of our study was to investigate the expression of guanine nucleotide exchange factor Dock180 in ovarian tumor, and its significance in the initiation and progression of ovarian cancer.Methods: Immunohistochemical staining with SP method was conducted to identify the expression of Dock180 protein in epithelial ovarian tumor in 68 cases.Results: Dock180 present with higher expression in ovarian cancer, as compared with than that in low malignant tumor and benign ovarian tumor (P < 0.01).In ovarian cancer, Dock180 expression was increased with the increased FIGO stage and grade.Conclusion: Dock180 overexpression may play an important role in the development and progression of ovarian cancer and it could be used as a new measurement of malignant biological behavior of ovarian cancer.

  14. Genomic analysis of epithelial ovarian cancer

    Institute of Scientific and Technical Information of China (English)

    John Farley; Laurent L Ozbun; Michael J Birrer

    2008-01-01

    Ovarian cancer is a major health problem for women in the United States.Despite evidence of considerable heterogeneity,most cases of ovarian cancer are treated in a similar fashion.The molecular basis for the clinicopathologic characteristics of these tumors remains poorly defined.Whole genome expression profiling is a genomic tool,which can identify dysregulated genes and uncover unique sub-classes of tumors.The application of this technology to ovarian cancer has provided a solid molecular basis for differences in histology and grade of ovarian tumors.Differentially expressed genes identified pathways implicated in cell proliferation,invasion,motility,chromosomal instability,and gene silencing and provided new insights into the origin and potential treatment of these cancers.The added knowledge provided by global gene expression profiling should allow for a more rational treatment of ovarian cancers.These techniques are leading to a paradigm shift from empirical treatment to an individually tailored approach.This review summarizes the new genomic data on epithelial ovarian cancers of different histology and grade and the impact it will have on our understanding and treatment of this disease.

  15. Microarray expression analysis of epithelial ovarian cancer with distinct differentiation

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    To identify gene expression profiling in epithelial ovarian cancer and to explore its correlation with histopathology characterization and prognosis. Gene expression profiles were generated from 10 human ovarian frozen tissue specimens using Agilent Human 1A microarrays. Strikingly, clear differences of gene expression patterns were observed in ovarian cancer as compared to normal tissues. Unique gene profiles were observed in moderately and poorly differentiated epithelial ovarian cancer. It is concluded that different histopathology characterization likely exists extensive molecular heterogeneity.

  16. Cytoreductive Surgery plus Hyperthermic Intraperitoneal Chemotherapy to Treat Advanced/Recurrent Epithelial Ovarian Cancer: Results from a Retrospective Study on Prospectively Established Database

    Directory of Open Access Journals (Sweden)

    Jian-Hua Sun

    2016-04-01

    Full Text Available BACKGROUND: Despite the best standard treatment, optimal cytoreductive surgery (CRS and platinum/taxane-based chemotherapy, prognosis of advanced epithelial ovarian carcinoma (EOC remains poor. Recently, CRS plus hyperthermic intraperitoneal chemotherapy (HIPEC has been developed to treat peritoneal carcinomatosis (PC. This study was to evaluate the efficacy and safety of CRS+HIPEC to treat PC from advanced/recurrent EOC. METHODS: Forty-six PC patients from advanced EOC (group A or recurrent EOC (group B were treated by 50 CRS+HIPEC procedures. The primary endpoints were progression-free survival (PFS and overall survival (OS; the secondary endpoints were safety profiles. RESULTS: The median OS was 74.0 months [95% confidence interval (CI 8.5-139.5] for group A versus 57.5 months (95% CI 29.8-85.2 for group B (P = .68. The median PFS was not reached for group A versus 8.5 months (95% CI 0-17.5 for group B (P = .034. Better median OS correlated with peritoneal cancer index (PCI 20 group, P = .01, complete cyroreduction (residual disease ≤ 2.5 mm [79.5 months for completeness of cytoreduction (CC score 0-1 vs 24.3 months for CC 2-3, P = .00], and sensitivity to platinum (65.3 months for platinum-sensitive group vs 20.0 for platinum-resistant group, P = .05. Serious adverse events occurred in five patients (10.0%. Multivariate analysis identified CC score as the only independent factor for better survival. CONCLUSION: For advanced/recurrent EOC, CRS+HIPEC could improve OS with acceptable safety.

  17. Epithelial ovarian cancer: testing the 'androgens hypothesis'.

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    Olsen, Catherine M; Green, Adèle C; Nagle, Christina M; Jordan, Susan J; Whiteman, David C; Bain, Christopher J; Webb, Penelope M

    2008-12-01

    In 1998, Risch proposed a hypothesis for the pathogenesis of ovarian cancer relating to the role of androgens in stimulating epithelial cell proliferation. Although this hypothesis has been widely discussed, direct evidence to support it is scant. To address this issue, we have conducted a detailed analysis of factors possibly associated with high circulating levels of androgens, including polycystic ovary syndrome (PCOS), hirsutism and acne (all clinically associated with hyperandrogenism) using the data collected in an Australia-wide, population-based case-control study. Cases aged 18-79 years with a new diagnosis of invasive epithelial ovarian cancer (n=1276) or borderline malignant tumour (n=315) were identified through a network of clinics and cancer registries throughout Australia. Controls (n=1508) were selected from the National Electoral Roll. Women self-reported a history of PCOS, acne, hirsutism and also use of testosterone supplements or the androgenic medication Danazol. We found no evidence that a history of PCOS, acne or hirsutism was associated with ovarian cancer overall, or with specific subtypes, with the exception of serous borderline tumours that were positively associated with a history of PCOS (OR 2.6; 95% CI 1.0-6.1). Women who had ever used testosterone supplements had an increased risk of ovarian cancer (OR 3.7; 95% CI 1.1-12.0); however, use of the androgenic medication Danazol did not increase risk (OR 1.0; 95% CI 0.4-2.9). Overall, our results do not support the hypothesis that androgen-related disorders increase the risk of ovarian cancer.

  18. Analysis of the TGFβ functional pathway in epithelial ovarian carcinoma

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    Francis-Thickpenny, K M; Richardson, D M; Ee, C C van; Love, D R; Winship, I M; Baguley, B C; Chenevix-Trench, G; Shelling, A N

    2001-01-01

    Epithelial ovarian carcinoma is often diagnosed at an advanced stage of disease and is the leading cause of death from gynaecological neoplasia. The genetic changes that occur during the development of this carcinoma are poorly understood. It has been proposed that IGFIIR, TGFβ1 and TGFβRII act as a functional unit in the TGFβ growth inhibitory pathway, and that somatic loss-of-function mutations in any one of these genes could lead to disruption of the pathway and subsequent loss of cell cycle control. We have examined these 3 genes in 25 epithelial ovarian carcinomas using single-stranded conformational polymorphism analysis and DNA sequence analysis. A total of 3 somatic missense mutations were found in the TGFβRII gene, but none in IGFRII or TGFβ1. An association was found between TGFβRII mutations and histology, with 2 out of 3 clear cell carcinomas having TGFβRII mutations. This data supports other evidence from mutational analysis of the PTEN and β-catenin genes that there are distinct developmental pathways responsible for the progression of different epithelial ovarian cancer histologic subtypes. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11531253

  19. Genetic analysis of the early natural history of epithelial ovarian carcinoma.

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    Bhavana Pothuri

    Full Text Available BACKGROUND: The high mortality rate associated with epithelial ovarian carcinoma (EOC reflects diagnosis commonly at an advanced stage, but improved early detection is hindered by uncertainty as to the histologic origin and early natural history of this malignancy. METHODOLOGY/PRINCIPAL FINDINGS: Here we report combined molecular genetic and morphologic analyses of normal human ovarian tissues and early stage cancers, from both BRCA mutation carriers and the general population, indicating that EOCs frequently arise from dysplastic precursor lesions within epithelial inclusion cysts. In pathologically normal ovaries, molecular evidence of oncogenic stress was observed specifically within epithelial inclusion cysts. To further explore potential very early events in ovarian tumorigenesis, ovarian tissues from women not known to be at high risk for ovarian cancer were subjected to laser catapult microdissection and gene expression profiling. These studies revealed a quasi-neoplastic expression signature in benign ovarian cystic inclusion epithelium compared to surface epithelium, specifically with respect to genes affecting signal transduction, cell cycle control, and mitotic spindle formation. Consistent with this gene expression profile, a significantly higher cell proliferation index (increased cell proliferation and decreased apoptosis was observed in histopathologically normal ovarian cystic compared to surface epithelium. Furthermore, aneuploidy was frequently identified in normal ovarian cystic epithelium but not in surface epithelium. CONCLUSIONS/SIGNIFICANCE: Together, these data indicate that EOC frequently arises in ovarian cystic inclusions, is preceded by an identifiable dysplastic precursor lesion, and that increased cell proliferation, decreased apoptosis, and aneuploidy are likely to represent very early aberrations in ovarian tumorigenesis.

  20. Cells of Origin of Epithelial Ovarian Cancers

    Science.gov (United States)

    2015-09-01

    AWARD NUMBER: W81XWH-14-1-0280 TITLE: Cells of Origin of Epithelial Ovarian Cancers PRINCIPAL INVESTIGATOR: Zhe Li, PhD CONTRACTING...Xie, Zhe Li 5d. PROJECT NUMBER 5e. TASK NUMBER E-Mail: zli4@rics.bwh.harvard.edu 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND...Lined Inclusion Cysts or Teratomas. PLoS ONE 8, e65067. Sherman-Baust, C.A., Kuhn, E., Valle, B.L., Shih Ie, M., Kurman, R.J., Wang , T.L., Amano, T

  1. Correlation between epithelial ovarian cancer and thrombocytosis%卵巢上皮性癌和血小板计数增高相关性分析

    Institute of Scientific and Technical Information of China (English)

    Zhiyi Liang; Hong Zhang

    2009-01-01

    Objective: To evaluate the clinical significance of platelet (PLT) count in epithelial ovarian cancer, and to inves-tigate 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, histo-pathology, 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)×109/L in the early stage epithelial ovarian cancer group, (308.12±111.95)×10/L in the advanced stage epithelial ovarian cancer group,and (206.28±52.62)×109/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.

  2. PROGNOSIS OF EPITHELIAL OVARIAN CANCER RELATED TO ITS ASCITES

    Institute of Scientific and Technical Information of China (English)

    宋水勤; 张国楠; 吴艳丽; 周红; 赵素兰; 谢方; 陈毅男

    2001-01-01

    Objective: To investigate the relationship between the prognosis of Epithelial Ovarian Cancer (EOC) and its ascites. Methods: Retrospectively analysis is performed for the clinical, pathological and followed up data of 101 in-patients suffering from epithelial ovarian cancer and operated with tumor debulking surgery in our hospital from January 1986 to December 1993. The patients was divided into two groups based upon the first laparotomy finding with ascites(62) or without(39). Age average, cell type, advanced proportion and survival rate of the patients are evaluated by a c2 test. Results: For age average and cell type, no statistical difference was noted. However, there were more advanced cases in ascites group than in the other (P<0.01). The 3-, 4- and 5-year survival in the no-ascites group were 87.02%, 73.42%, 57.10% respectively compared with 65.02%, 38.66%, 28.12% in the ascites group. The 5-year survival rate of stage I, II,III, IV patients in no-ascites group are 77%, 70%, 41.1%, 0 respectively, compared with that of 60%, 56.8%, 15.46%, 0 respectively in the ascites group. The results shows that 3-, 4-, and 5-year survival in no-ascites group were significantly higher than those in ascites group(P<0.01). Conclusion: Presence of ascites is a factor of poor prognosis for EOC.

  3. CXCL12 expression by healthy and malignant ovarian epithelial cells

    Directory of Open Access Journals (Sweden)

    Emilie Dominique

    2011-03-01

    Full Text Available Abstract Background CXCL12 has been widely reported to play a biologically relevant role in tumor growth and spread. In epithelial ovarian cancer (EOC, CXCL12 enhances tumor angiogenesis and contributes to the immunosuppressive network. However, its prognostic significance remains unclear. We thus compared CXCL12 status in healthy and malignant ovaries, to assess its prognostic value. Methods Immunohistochemistry was used to analyze CXCL12 expression in the reproductive tracts, including the ovaries and fallopian tubes, of healthy women, in benign and borderline epithelial tumors, and in a series of 183 tumor specimens from patients with advanced primary EOC enrolled in a multicenter prospective clinical trial of paclitaxel/carboplatin/gemcitabine-based chemotherapy (GINECO study. Univariate COX model analysis was performed to assess the prognostic value of clinical and biological variables. Kaplan-Meier methods were used to generate progression-free and overall survival curves. Results Epithelial cells from the surface of the ovary and the fallopian tubes stained positive for CXCL12, whereas the follicles within the ovary did not. Epithelial cells in benign, borderline and malignant tumors also expressed CXCL12. In EOC specimens, CXCL12 immunoreactivity was observed mostly in epithelial tumor cells. The intensity of the signal obtained ranged from strong in 86 cases (47% to absent in 18 cases ( Conclusion Our findings highlight the previously unappreciated constitutive expression of CXCL12 on healthy epithelia of the ovary surface and fallopian tubes, indicating that EOC may originate from either of these epithelia. We reveal that CXCL12 production by malignant epithelial cells precedes tumorigenesis and we confirm in a large cohort of patients with advanced EOC that CXCL12 expression level in EOC is not a valuable prognostic factor in itself. Trial Registration ClinicalTrials.gov: NCT00052468

  4. Screening of the residual normal ovarian tissue adjacent to orthotopic epithelial ovarian carcinomas in nude mice.

    Science.gov (United States)

    Zhu, G H; Wang, S T; Yao, M Z; Cai, J H; Chen, C Y; Yang, Z X; Hong, L; Yang, S Y

    2014-04-16

    The objective of this study was to explore the feasibility and methods of screening the residual normal ovarian tissue adjacent to orthotopic ovarian carcinomas in nude mice. Human epithelial ovarian cancer cells (OVCAR3) were subcutaneously implanted for a tumor source and ovarian orthotopic transplantation. The cancer tissue, proximal paraneoplastic tissue, middle paraneoplastic tissue, remote paraneoplastic tissue, and normal ovarian tissue were removed. CK-7, CA125, p53, survivin, MMP-2, and TIMP-2 expression was detected by reverse transcription polymerase chain reaction. We obtained 35 paraneoplastic residual ovarian tissues with normal biopsies from 40 cases of an orthotopic epithelial ovarian carcinoma model (87.5%). CK-7, CA125, p53, survivin, MMP-2, and TIMP-2 expression was lower in proximal paraneoplastic tissue than in cancer tissue (P tissue (P tissue as well as among residual normal ovarian tissues with different severity (P > 0.05). In ovarian tissues of 20 normal nude mice, the expression of CK- 7, CA125, p53, survivin, MMP-2, and TIMP-2 was negative. Overall, the expression levels of CK-7, CA125, p53, survivin, MMP-2, TIMP-2, and other molecular markers showed a decreasing trend in the non-cancer tissue direction. The expression levels can be used as standards to screen residual normal ovarian tissue. We can obtain relatively safe normal ovarian tissues adjacent to epithelial ovarian cancer.

  5. Chronic Recreational Physical Inactivity and Epithelial Ovarian Cancer Risk

    DEFF Research Database (Denmark)

    Cannioto, Rikki; LaMonte, Michael J; Risch, Harvey A

    2016-01-01

    BACKGROUND: Despite a large body of literature evaluating the association between recreational physical activity and epithelial ovarian cancer (EOC) risk, the extant evidence is inconclusive, and little is known about the independent association between recreational physical inactivity and EOC ri...

  6. Risk factors of epithelial ovarian carcinomas among women with endometriosis

    DEFF Research Database (Denmark)

    Thomsen, Line Holdgaard; Schnack, Tine H; Buchardi, Kristina

    2016-01-01

    of endometriotic tissue and suggested among women with unilateral oophorectomy. The use of oral contraceptives (≥10 years) may be associated with a lower risk of epithelial ovarian cancer among women with endometriosis, whereas older age at endometriosis diagnosis (≥45 years, pre- or postmenopausal), nulliparity......INTRODUCTION: To evaluate the published literature on epidemiologic risk factors for epithelial ovarian cancer among women with a diagnosis of endometriosis. MATERIAL AND METHODS: A systematic literature search was conducted in PubMed and Scopus. Studies comparing epidemiologic risk factors...... of epithelial ovarian cancer among women with endometriosis were included. A quality assessment was conducted using the Newcastle-Ottawa Scale. RESULTS: Eight of 794 articles met the inclusion criteria. A lower risk of epithelial ovarian cancer was observed in women with documented complete surgical excision...

  7. Lack of relationship between EGFR-1 immunohistochemical expression and prognosis in a multicentre clinical trial of 93 patients with advanced primary ovarian epithelial cancer (GINECO group).

    Science.gov (United States)

    Elie, C; Geay, J F; Morcos, M; Le Tourneau, A; Girre, V; Broët, P; Marmey, B; Chauvenet, L; Audouin, J; Pujade-Lauraine, E; Camilleri-Broët, S

    2004-08-02

    Epidermal growth factor receptor 1 (EGFR-1) overexpression is usually described as linked with a worse prognosis in a variety of tumours of epithelial origin. However, its role in ovarian cancer is still controversial. The aim of the present study was to analyse the prognostic impact of EGFR-1 in a retrospective series of 93 stage III-IV primary ovarian epithelial tumours. All patients, enrolled in a multicentre GINECO prospective clinical trial, were treated with the same platinum-based combination chemotherapy, and were followed up with a median of 69 months. Epidermal growth factor receptor 1 plasma membrane expression, assessed by immunohistochemistry on paraffin-embedded tissues, was correlated with clinical parameters as well as immunohistochemical expression results of HER-2 (c-erbB-2), BAX, BCL-2, p53 and anti-Ki-67, previously studied in the same series of patients. Positive immunostaining for EGFR-1 was seen in 31 of the 93 analysed cases (33%). No correlation was found between EGFR-1 expression and clinical parameters. No correlation was found between EGFR-1 expression and other biological markers, except for HER-2, which was limit for significance. Indeed, among the EGFR-1-negative cases, 10.3% expressed HER-2, whereas the HER-2-expressing tumours accounted for 27.6% of EGFR-1-positive cases (P=0.06). Epidermal growth factor receptor 1 overexpression had no prognostic impact on both overall and progression-free survival through univariate and multivariate analyses. The potential effect of EGFR-1 and HER-2 co-expression on targeted therapy against EGFR-1 and/or HER-2 molecules has to be further analysed.

  8. The effect of debulking surgery after induction chemotherapy on the prognosis in advanced epithelial ovarian cancer. Gynecological Cancer Cooperative Group of the European Organization for Research and Treatment of Cancer

    NARCIS (Netherlands)

    M.E.L. van der Burg (Maria); M. van Lent; M. Buyse; A. Kobierska; N. Colombo; G. Favalli; A.J. Lacave; M. Nardi; J. Renard; S. Pecorelli (Sergio)

    1995-01-01

    textabstractBACKGROUND. Although the value of primary cytoreductive surgery for epithelial ovarian cancer is beyond doubt, the value of debulking surgery after induction chemotherapy has not yet been defined. In this randomized study we investigated the effect on surviv

  9. Epidemiology of epithelial ovarian cancer, a single institution-based study in India

    Directory of Open Access Journals (Sweden)

    Surendra Kumar Saini

    2016-01-01

    Full Text Available Background: Ovarian cancer is the leading cause of mortality among all cancers of female genital tract in countries where effective cervical cancer screening program exists. As the world's population ages, remarkable increase in the total number of ovarian cancer cases are expected. This is preliminary epidemiological study to decide priorities in ovarian cancer research. Materials and Methods: A retrospective study was conducted with primary epithelial ovarian cancer cases registered in J. K. Cancer Institute, Kanpur (Uttar Pradesh, from 2007 to 2009. Patients' age at diagnosis, clinical feature, parity of patients, tumor histological type, Federation of Gynecology and Obstetrics stage, chemotherapy regimens, and overall survival data were collected and analyzed. Results: One hundred and sixty-three cases of primary ovarian epithelial cancer were analyzed. Patients' mean age at diagnosis was 55.98 ± 9.24 (median = 55. Serous adenocarcinoma (49.69% was the most prevalent type of histopathology followed by endometroid (19.1%, mucinous (10.42% and clear cell (4.29%. Combination of taxane and platin was most commonly used first line regimen in newly diagnosed as well as in relapsed patients post 1 year. Survival was not significantly different in various histopathology (log-rank P = 0.7406, but advancing stage demonstrated gradually poor survival (log-rank P < 0.05 when compared with early stage disease. Conclusion: Research efforts should be in the direction to find early diagnostic and effective screening tools as well as better therapeutic approaches for advanced epithelial ovarian cancer.

  10. ELF5 in epithelial ovarian carcinoma tissues and biological behavior in ovarian carcinoma cells.

    Science.gov (United States)

    Yan, Hongchao; Qiu, Linglin; Xie, Xiaolei; Yang, He; Liu, Yongli; Lin, Xiaoman; Huang, Hongxiang

    2017-03-01

    The expression of E74-like factor 5 (ELF5) in epithelial ovarian carcinoma tissues and its effects on biological behavior in ovarian carcinoma cells were assessed in search for a new approach for gene treatment of epithelial ovarian carcinoma. RT-PCR technology was applied to detect the expression of ELF5 mRNA in epithelial ovarian carcinoma (n=49), borderline ovarian epithelial tumor (n=19), benign ovarian epithelial tumor (n=31) and normal ovarian tissues (n=40). Then, we transfected recombinant plasmid pcDNA3.1‑ELF5+EGFP into human ovarian carcinoma SKOV3 cells (recombinant plasmid group) in vitro and screened out stably transfected cells to conduct multiplication culture. Western blot analysis was performed to detect the expression of ELF5 protein in the different groups. Flow cytometry was employed to detect cell apoptosis and cycles. ELF5 mRNA in epithelial ovarian carcinoma and borderline ovarian epithelial tumor tissues were significantly lower (Pepithelial tumor and normal ovarian tissues. ELF5 protein expression in the cells of recombinant plasmid group was significantly higher compared with empty plasmid and blank control groups. The capacity of cell reproductive recombinant plasmid group at each time point decreased (P<0.05). Flow cytometry detection showed that 67.03% of cells in recombinant plasmid group was blocked in G0/G1 phase (P<0.05), compared with empty plasmid group (37.17%) and blank control group (38.24%). Apoptotic rate of recombinant plasmid group was significantly lower (31.4±1.9%; P<0.05), compared with that of empty plasmid group (9.1±2.2%) and blank control group (8.7±1.5%), and the differences were statistically significant. In conclusion, ELF5 interfered with cell cycle of human ovarian carcinoma SKOV3 cells and promoted apoptosis of human ovarian carcinoma SKOV3 cells inhibiting their growth and invasive capacity; and thus providing a new approach to gene treatment of ovarian carcinoma.

  11. Comparative proteome analysis of human epithelial ovarian cancer

    Directory of Open Access Journals (Sweden)

    Gagné Jean-Philippe

    2007-09-01

    Full Text Available Abstract Background Epithelial ovarian cancer is a devastating disease associated with low survival prognosis mainly because of the lack of early detection markers and the asymptomatic nature of the cancer until late stage. Using two complementary proteomics approaches, a differential protein expression profile was carried out between low and highly transformed epithelial ovarian cancer cell lines which realistically mimic the phenotypic changes observed during evolution of a tumour metastasis. This investigation was aimed at a better understanding of the molecular mechanisms underlying differentiation, proliferation and neoplastic progression of ovarian cancer. Results The quantitative profiling of epithelial ovarian cancer model cell lines TOV-81D and TOV-112D generated using iTRAQ analysis and two-dimensional electrophoresis coupled to liquid chromatography tandem mass spectrometry revealed some proteins with altered expression levels. Several of these proteins have been the object of interest in cancer research but others were unrecognized as differentially expressed in a context of ovarian cancer. Among these, series of proteins involved in transcriptional activity, cellular metabolism, cell adhesion or motility and cytoskeleton organization were identified, suggesting their possible role in the emergence of oncogenic pathways leading to aggressive cellular behavior. Conclusion The differential protein expression profile generated by the two proteomics approaches combined to complementary characterizations studies will open the way to more exhaustive and systematic representation of the disease and will provide valuable information that may be helpful to uncover the molecular mechanisms related to epithelial ovarian cancer.

  12. Epithelial ovarian tumors: Clinicopathological correlation and immunohistochemical study

    OpenAIRE

    2015-01-01

    Background: Ovarian cancer is the third leading site of cancer among women, trailing behind cervix and breast cancer. Aim: This study was undertaken to analyze the immunohistochemical (IHC) profile of estrogen receptors (ER), progesterone receptors (PR), Ki-67, and p53 in various ovarian epithelial tumors and attempt correlation with clinical and histopathological findings. Materials and Methods: The present study was conducted over a period of 4 years. A technique of manual tissue ar...

  13. Clinical Use of Cancer Biomarkers in Epithelial Ovarian Cancer

    DEFF Research Database (Denmark)

    Söletormos, Georg; Duffy, Michael J; Othman Abu Hassan, Suher

    2016-01-01

    OBJECTIVE: To present an update of the European Group on Tumor Markers guidelines for serum markers in epithelial ovarian cancer. METHODS: Systematic literature survey from 2008 to 2013. The articles were evaluated by level of evidence and strength of recommendation. RESULTS: Because of its low...... for secondary cytoreductive surgery. CONCLUSIONS: At present, CA125 remains the most important biomarker for epithelial ovarian cancer, excluding tumors of mucinous origin.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4...

  14. Is There a Relationship between Ovarian Epithelial Dysplasia and Infertility?

    Directory of Open Access Journals (Sweden)

    Gautier Chene

    2012-01-01

    Full Text Available Aim. Ovarian epithelial dysplasia was initially described in material from prophylactic oophorectomies performed in patients at genetic risk of ovarian cancer. Similar histopathological abnormalities have been revealed after ovulation stimulation. Since infertility is also a risk factor for ovarian neoplasia, the aim of this study was to study the relationship between infertility and ovarian dysplasia. Methods. We blindly reviewed 127 histopathological slides of adnexectomies or ovarian cystectomies according to three groups—an exposed group to ovulation induction (n = 30, an infertile group without stimulation (n = 35, and a spontaneously fertile control group (n = 62—in order to design an eleven histopathological criteria scoring system. Results. The ovarian dysplasia score was significantly higher in exposed group whereas dysplasia score was low in infertile and control groups (resp., 8.21 in exposed group, 3.69 for infertile patients, and 3.62 for the controls. In the subgroup with refractory infertility there was a trend towards a more severe dysplasia score (8.53 in ovulation induction group and 5.1 in infertile group. Conclusion. These results raise questions as to the responsibility of drugs used to induce ovulation and/or infertility itself in the genesis of ovarian epithelial dysplasia.

  15. Peritoneal inflammation – A microenvironment for Epithelial Ovarian Cancer (EOC

    Directory of Open Access Journals (Sweden)

    Liu Jinsong

    2004-06-01

    Full Text Available Abstract Epithelial ovarian cancer (EOC is a significant cause of cancer related morbidity and mortality in women. Preferential involvement of peritoneal structures contributes to the overall poor outcome in EOC patients. Advances in biotechnology, such as cDNA microarray, are a product of the Human Genome Project and are beginning to provide fresh opportunities to understand the biology of EOC. In particular, it is now possible to examine in depth, at the molecular level, the complex relationship between the tumor itself and its surrounding microenvironment. This review focuses on the anatomy, physiology, and current immunobiologic research of peritoneal structures, and addresses certain potentially useful animal models. Changes in both the inflammatory and non-inflammatory cell compartments, as well as alterations to the extracellular matrix, appear to be signal events that contribute to the remodeling effects of the peritoneal stroma and surface epithelial cells on tumor growth and spread. These alterations may involve a number of proteins, including cytokines, chemokines, growth factors, either membrane or non-membrane bound, and integrins. Interactions between these molecules and molecular structures within the extracellular matrix, such as collagens and the proteoglycans, may contribute to a peritoneal mesothelial surface and stromal environment that is conducive to tumor cell proliferation and invasion. These alterations need to be examined and defined as possible prosnosticators and as therapeutic or diagnostic targets.

  16. Targeted therapies in epithelial ovarian cancer: Molecular mechanisms of action

    Institute of Scientific and Technical Information of China (English)

    Hiroaki; Itamochi

    2010-01-01

    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.

  17. General Information about Ovarian Epithelial Cancer

    Science.gov (United States)

    ... peritoneal cancer include pain or swelling in the abdomen. Ovarian, fallopian tube, or peritoneal cancer may not ... swelling, or a feeling of pressure in the abdomen or pelvis. Vaginal bleeding that is heavy or ...

  18. Chemokine Receptors in Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Goda G. Muralidhar

    2013-12-01

    Full Text Available Ovarian carcinoma is the deadliest gynecologic malignancy with very poor rate of survival, and it is characterized by the presence of vast incurable peritoneal metastasis. Studies of the role of chemokine receptors, a family of proteins belonging to the group of G protein-coupled receptors, in ovarian carcinoma strongly placed this family of membrane receptors as major regulators of progression of this malignancy. In this review, we will discuss the roles that chemokine-receptor interactions play to support angiogenesis, cell proliferation, migration, adhesion, invasion, metastasis, and immune evasion in progression of ovarian carcinoma. Data regarding the role that the chemokine receptors play in the disease progression accumulated insofar strongly suggest that this family of proteins could be good therapeutic targets against ovarian carcinoma.

  19. Assessing the genetic architecture of epithelial ovarian cancer histological subtypes

    DEFF Research Database (Denmark)

    Cuellar-Partida, Gabriel; Lu, Yi; Dixon, Suzanne C

    2016-01-01

    Epithelial ovarian cancer (EOC) is one of the deadliest common cancers. The five most common types of disease are high-grade and low-grade serous, endometrioid, mucinous and clear cell carcinoma. Each of these subtypes present distinct molecular pathogeneses and sensitivities to treatments. Recen...

  20. Nesfatin-1 inhibits ovarian epithelial carcinoma cell proliferation in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Yang; Pang, Xiaoyan; Dong, Mei; Wen, Fang, E-mail: wenfang64@hotmail.com; Zhang, Yi, E-mail: syzi960@yahoo.com

    2013-11-01

    Highlights: •Nesfatin-1 inhibits the proliferation and growth of HO-8910 cells by G1 phase arrest. •Nesfatin-1 enhances HO-8910 cell apoptosis. •Nesfatin-1 inhibits HO-8910 cell proliferation via mTOR and RhoA/ROCK signaling pathway. •The first report of nesfatin-1-mediated proliferation in ovarian epithelial carcinoma. -- Abstract: Nesfatin-1, an 82-amino-acid peptide derived from a 396-amino-acid precursor protein nucleobindin 2 (NUCB2), was originally identified in hypothalamic nuclei involved in the regulation of food intake. It was recently reported that nesfatin-1 is a novel depot specific adipokine preferentially produced by subcutaneous tissue, with obesity- and food deprivation-regulated expression. Although a relation between ovarian cancer mortality and obesity has been previously established, a role of nesfatin-1 in ovarian epithelial carcinoma remains unknown. The aim of the present study is to examine the effect of nesfatin-1 on ovary carcinoma cells proliferation. We found that nesfatin-1 inhibits the proliferation and growth of HO-8910 cells by G1 phase arrest, this inhibition could be abolished by nesfatin-1 neutralizing antibody. Nesfatin-1 enhances HO-8910 cell apoptosis, activation of mammalian target of rapamycin (mTOR) and RhoA/ROCK signaling pathway block the effects of nesfatin-1-induced apoptosis, therefore reverses the inhibition of HO-8910 cell proliferation by nesfatin-1. In conclusion, the present study demonstrated that nesfatin-1 can inhibit the proliferation in human ovarian epithelial carcinoma cell line HO-8910 cells through inducing apoptosis via mTOR and RhoA/ROCK signaling pathway. This study provides a novel regulatory signaling pathway of nesfatin-1-regulated ovarian epithelial carcinoma growth and may contribute to ovarian cancer prevention and therapy, especially in obese patients.

  1. Validation of epithelial ovarian cancer and fallopian tube cancer and ovarian borderline tumor data in the Danish Gynecological Cancer Database

    DEFF Research Database (Denmark)

    Petri, A.L.; Kjaer, S.K.; Christensen, I.J.;

    2009-01-01

    OBJECTIVE: To validate the data on epithelial ovarian cancer, fallopian tube cancer and borderline ovarian tumors registered in the nationwide Danish Gynecological Cancer Database (DGCD) in 2005 and 2006. The DGCD is a multidisciplinary database that contains data for research and quality......: The validity of ovarian cancer data in the DGCD is sufficient for quality monitoring in gynecological oncology Udgivelsesdato: 2009...

  2. Validation of epithelial ovarian cancer and fallopian tube cancer and ovarian borderline tumor data in the Danish Gynecological Cancer Database

    DEFF Research Database (Denmark)

    Petri, Anette Lykke; Kjaer, Susanne Krüger; Christensen, Ib J;

    2009-01-01

    OBJECTIVE: To validate the data on epithelial ovarian cancer, fallopian tube cancer and borderline ovarian tumors registered in the nationwide Danish Gynecological Cancer Database (DGCD) in 2005 and 2006. The DGCD is a multidisciplinary database that contains data for research and quality......: The validity of ovarian cancer data in the DGCD is sufficient for quality monitoring in gynecological oncology....

  3. Prevalence of epithelial ovarian cancer stem cells correlates with recurrence in early-stage ovarian cancer

    DEFF Research Database (Denmark)

    Steffensen, Karina Dahl; Alvero, Ayesha B; Yang, Yingkui

    2011-01-01

    Epithelial ovarian cancer stem cells (EOC stem cells) have been associated with recurrence and chemoresistance. CD44 and CK18 are highly expressed in cancer stem cells and function as tools for their identification and characterization. We investigated the association between the number of CD44+ ...

  4. Estrogen, Progesterone and Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Ho Shuk-Mei

    2003-10-01

    Full Text Available Abstract Ovarian carcinoma (OCa continues to be the leading cause of death due to gynecologic malignancies and the vast majority of OCa is derived from the ovarian surface epithelium (OSE and its cystic derivatives. Epidemiological evidence strongly suggests that steroid hormones, primarily estrogens and progesterone, are implicated in ovarian carcinogenesis. However, it has proved difficult to fully understand their mechanisms of action on the tumorigenic process. New convincing data have indicated that estrogens favor neoplastic transformation of the OSE while progesterone offers protection against OCa development. Specifically, estrogens, particularly those present in ovulatory follicles, are both genotoxic and mitogenic to OSE cells. In contrast, pregnancy-equivalent levels progesterone are highly effective as apoptosis inducers for OSE and OCa cells. In this regard, high-dose progestin may exert an exfoliation effect and rid an aged OSE of pre-malignant cells. A limited number of clinical studies has demonstrated efficacies of antiestrogens, aromatase inhibitors, and progestins alone or in combination with chemotherapeutic drugs in the treatment of OCa. As a result of increased life expectancy in most countries, the number of women taking hormone replacement therapies (HRT continues to grow. Thus, knowledge of the mechanism of action of steroid hormones on the OSE and OCa is of paramount significance to HRT risk assessment and to the development of novel therapies for the prevention and treatment of OCa.

  5. Expression of Beta-Catenin and APC Protein in Ovarian Epithelial Tumor and Its Implication

    Institute of Scientific and Technical Information of China (English)

    LIN Xiao; LI Yu; MI Can

    2007-01-01

    Objective: To investigate the expression of beta-catenin, APC protein and its implication in ovarian epithelial tumor. Methods: Immunohistochemical staining with SP method was conducted to determine the expression of beta-catenin and APC protein in 48 cases of ovarian epithelial tumor. Results: The abnormal expression rates of beta-catenin in ovarian malignant and borderline epithelial tumors were higher than that in benign epithelial tumors. The expression of APC protein in benign epithelial tumors was significantly greater than that in malignant epithelial tumors. A significant negative correlation was found between beta-catenin and APC protein in ovarian epithelial tumors. Conclusion: Beta-catenin and APC protein have important effect on pathogenesis and development of ovarian epithelial tumors.

  6. Common alleles in candidate susceptibility genes associated with risk and development of epithelial ovarian cancer

    DEFF Research Database (Denmark)

    Notaridou, Maria; Quaye, Lydia; Dafou, Dimitra;

    2011-01-01

    Common germline genetic variation in the population is associated with susceptibility to epithelial ovarian cancer. Microcell-mediated chromosome transfer and expression microarray analysis identified nine genes associated with functional suppression of tumorogenicity in ovarian cancer cell lines...

  7. Role of prevention and screening in epithelial ovarian cancer

    Directory of Open Access Journals (Sweden)

    Peddireddi Reddi Rani

    2015-08-01

    Full Text Available Epithelial ovarian carcinoma is a disease with poor prognosis and high mortality among gynaecological cancers due to inaccessibility of ovary for inspection or sampling and lack of proper screening methods. Strategies to detect early ovarian cancer include estimation of serum CA-125 and transvaginal ultrasound (TVS for morphological index. Studies have shown that screening of asymptomatic average risk post-menopausal women did not show any benefit and are associated with false positive results which may lead to unnecessary surgery and resultant morbidity. The risks outweigh benefits. Present recommendation is to screen high risk women especially hereditary cancers and offer risk reducing surgery when needed. Prophylactic salpingectomy/oophorectomy may offer the opportunity to prevent ovarian cancer. More trials and more research in newer biomarkers are needed. [Int J Reprod Contracept Obstet Gynecol 2015; 4(4.000: 941-946

  8. Randomised Trial Comparing Two Combination Chemotherapy Regimens (HEXA-CAF VS CHAP-5) In Advanced Ovarian Carcinoma

    NARCIS (Netherlands)

    Neijt, J.P.; Vriesendorp, R.; Burg, M.E.L. van der; Lindert, A.C.M. van; Lent, M.; Oosterom, A.T. van; Kooyman, C.D.; Hamerlynck, J. V. T. H.; Houwelingen, J.C. van; Pinedo, H.M.; Bokkel Huinink, W.W. ten

    1984-01-01

    186 patients with advanced epithelial ovarian carcinoma were treated with either a combination of hexamethylmelamine, cyclophosphamide, methotrexate, and 5-fluorouracil (Hexa-CAF) or cyclophosphamide and hexamethylmelamine alternating with doxorubicin and a 5-day course of cisplatin (CHAP-5). Treatm

  9. Lymphadenectomy in surgical stage I epithelial ovarian cancer

    DEFF Research Database (Denmark)

    Svolgaard, Olivia; Lidegaard, Ojvind; Nielsen, Marie Louise S;

    2014-01-01

    OBJECTIVE: To identify the extent of lymphadenectomy performed in women presenting with epithelial ovarian cancer macroscopically confined to the ovary. Furthermore, the effect of lymphadenectomy on overall survival is evaluated. DESIGN: A prospective nationwide case-only study. SETTING: Denmark......: Descriptive and survival analyses of data from Danish Gynecologic Cancer Database. MAIN OUTCOME MEASURES: The annual proportion of women with surgical stage I disease who received lymphadenectomy and the survival in the two groups. RESULTS: Of 2361 women with epithelial ovarian cancer, 627 were identified...... 2005-2011. SAMPLE: All women registered in the nationwide Danish Gynecologic Cancer Database from 1 January 2005 to 1 May 2011, presenting with a tumor macroscopically confined to the ovary without visible evidence of abdominal spread at the time of the initial exploration (surgical stage I). METHOD...

  10. Prevalence of human papillomavirus in epithelial ovarian cancer tissue. A meta-analysis of observational studies

    DEFF Research Database (Denmark)

    Svahn, Malene F; Faber, Mette Tuxen; Christensen, Jane

    2014-01-01

    The role of human papillomavirus (HPV) in the pathogenesis of ovarian cancer is controversial, and conflicting results have been published. We conducted a systematic review and meta-analysis to estimate the prevalence of HPV in epithelial ovarian cancer tissue.......The role of human papillomavirus (HPV) in the pathogenesis of ovarian cancer is controversial, and conflicting results have been published. We conducted a systematic review and meta-analysis to estimate the prevalence of HPV in epithelial ovarian cancer tissue....

  11. Targeting Signaling Pathways in Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Johannes Haybaeck

    2013-05-01

    Full Text Available Ovarian carcinoma (OC is the most lethal gynecological malignancy. Response to platinum-based chemotherapy is poor in some patients and, thus, current research is focusing on new therapy options. The various histological types of OC are characterized by distinctive molecular genetic alterations that are relevant for ovarian tumorigenesis. The understanding of these molecular pathways is essential for the development of novel therapeutic strategies. Purpose: We want to give an overview on the molecular genetic changes of the histopathological types of OC and their role as putative therapeutic targets. In Depth Review of Existing Data: In 2012, the vascular endothelial growth factor (VEGF inhibitor, bevacizumab, was approved for OC treatment. Bevacizumab has shown promising results as single agent and in combination with conventional chemotherapy, but its target is not distinctive when analyzed before treatment. At present, mammalian target of rapamycin (mTOR inhibitors, poly-ADP-ribose polymerase (PARP inhibitors and components of the EGFR pathway are in the focus of clinical research. Interestingly, some phytochemical substances show good synergistic effects when used in combination with chemotherapy. Conclusion: Ongoing studies of targeted agents in conjunction with chemotherapy will show whether there are alternative options to bevacizumab available for OC patients. Novel targets which can be assessed before therapy to predict efficacy are needed. The assessment of therapeutic targets is continuously improved by molecular pathological analyses on tumor tissue. A careful selection of patients for personalized treatment will help to reduce putative side effects and toxicity.

  12. Diffusion-weighted MRI of epithelial ovarian cancers: Correlation of apparent diffusion coefficient values with histologic grade and surgical stage

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Ji-Won, E-mail: fromentin@naver.com [Department of Radiology, Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 137-701 (Korea, Republic of); Rha, Sung Eun, E-mail: serha@catholic.ac.kr [Department of Radiology, Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 137-701 (Korea, Republic of); Oh, Soon Nam, E-mail: hiohsn@catholic.ac.kr [Department of Radiology, Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 137-701 (Korea, Republic of); Park, Michael Yong, E-mail: digirave@kmle.com [Department of Radiology, Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 137-701 (Korea, Republic of); Byun, Jae Young, E-mail: jybyun@catholic.ac.kr [Department of Radiology, Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 137-701 (Korea, Republic of); Lee, Ahwon, E-mail: klee@catholic.ac.kr [Department of Hospital Pathology, Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 137-701 (Korea, Republic of)

    2015-04-15

    Highlights: •The solid component of all invasive epithelial cancers showed high b{sub 1000} signal intensity. •ADCs can predict the histologic grade of epithelial ovarian cancer. •ADCs correlate negatively to the surgical stage of epithelial ovarian cancer. •ADCs may be useful imaging biomarkers to assess epithelial ovarian cancer. -- Abstract: Objective: The purpose of this article is to correlate the apparent diffusion coefficient (ADC) values of epithelial ovarian cancers with histologic grade and surgical stage. Materials and methods: We enrolled 43 patients with pathologically proven epithelial ovarian cancers for this retrospective study. All patients underwent preoperative pelvic magnetic resonance imaging (MRI) including diffusion-weighted images with b value of 0 and 1000 s/mm{sup 2} at 3.0-T unit. The mean ADC values of the solid portion of the tumor were measured and compared among different histologic grades and surgical stages. Results: The mean ADC values of epithelial ovarian cancers differed significantly between grade 1 (well-differentiated) and grade 2 (moderately-differentiated) (P = 0.013) as well as between grade 1 and grade 3 (poorly-differentiated) (P = 0.01); however, no statistically significant difference existed between grade 2 and grade 3 (P = 0.737). The receiver-operating characteristic analysis indicated that a cutoff ADC value of less than or equal to 1.09 × 10{sup −3} mm{sup 2}/s was associated with 94.4% sensitivity and 85.7% specificity in distinguishing grade 1 and grade 2/3 cancer. The difference in mean ADC values was statistically significant for early stage (FIGO stage I) and advanced stage (FIGO stage II-IV) cancer (P = 0.011). The interobserver agreement for the mean ADC values of epithelial ovarian cancers was excellent. Conclusion: The mean ADC values of the solid portion of epithelial ovarian cancers negatively correlated to histologic grade and surgical stage. The mean ADC values may be useful imaging

  13. CLINICAL VALUE OF SERUM TUMOR SUPPLIED GROUP OF FACTOR IN DIAGNOSIS OF EPITHELIAL OVARIAN CANCER

    Institute of Scientific and Technical Information of China (English)

    程琪辉; 张喜平; 曾小澜

    2003-01-01

    Objective: To evaluate the clinical value of serum tumor supplied group of factor (TSGF) in diagnosis of epithelial ovarian cancer. Methods: The serum TSGF was tested in 69 patients with epithelial ovarian cancer, 28 patients with benign ovarian lesion and 61 healthy women. The serum levels of vascular endothelial growth factor (VEGF) and CA125 were determined in patients with epithelial ovarian cancer and in those with benign ovarian lesion. The correlations of TSGF with VEGF and CA125 were investigated. Results: The serum level of TSGF in patients with epithelial ovarian cancer was obviously higher than in patients with benign ovarian lesion and in healthy women (P0.05). The serum level of TSGF and VEGF and CA125 in patients with epithelial ovarian cancer showed positive correlation (P<0.01, P<0.05, respectively). Conclusion: There is no marked difference in diagnostic value among TSGF, VEGF and CA125. TSGF has a certain value in diagnosis of epithelial ovarian cancer, and is helpful to distinguish epithelial ovarian cancer from benign ovarian lesion.

  14. Early Alterations in Ovarian Surface Epithelial Cells and Induction of Ovarian Epithelial Tumors Triggered by Loss of FSH Receptor

    Directory of Open Access Journals (Sweden)

    Xinlei Chen

    2007-06-01

    Full Text Available Little is known about the behavior of the ovarian surface epithelium (OSE, which plays a central role in ovarian cancer etiology. It has been suggested that incessant ovulation causes OSE changes leading to transformation and that high gonadotropin levels during postmenopause activate OSE receptors, inducing proliferation. We examined the chronology of OSE changes, including tumor appearance, in a mouse model where ovulation never occurs due to deletion of follitropin receptor. Changes in epithelial cells were marked by pan-cytokeratin (CK staining. Histologic changes and CK staining in the OSE increased from postnatal day 2. CK staining was observed inside the ovary by 24 days and increased thereafter in tumor-bearing animals. Ovaries from a third of aged (1 year mutant mice showed CK deep inside, indicating cell migration. These tumors resembled serous papillary adenoma of human ovaries. Weak expression of GATA-4 and elevation of PCNA, cyclooxygenase-1, cyclooxygenase-2, and plateletderived growth factor receptors α and β in mutants indicated differences in cell proliferation, differentiation, and inflammation. Thus, we report that OSE changes occur long before epithelial tumors appear in FORKO mice. Our results suggest that neither incessant ovulation nor follicle-stimulating hormone receptor presence in the OSE is required for inducing ovarian tumors; thus, other mechanisms must contribute to ovarian tumorigenesis.

  15. Current status of bevacizumab in advanced ovarian cancer

    Directory of Open Access Journals (Sweden)

    Tomao F

    2013-07-01

    Full Text Available Federica Tomao,1,* Anselmo Papa,2,* Luigi Rossi,2 Davide Caruso,2 Pierluigi Benedetti Panici,1 Martina Venezia,2 Silverio Tomao21Department of Gynaecology and Obstetrics, "Sapienza" University of Rome, Policlinico "Umberto I," Rome, Italy; 2Department of Medico-Surgical Sciences and Biotechnologies, "Sapienza" University of Rome, Oncology Unit, "ICOT," Latina, Italy*Authors contributed equally to this workAbstract: Ovarian cancer is the most lethal gynecological cancer, mainly because of the delay in diagnosis. Recently, much effort has been put into investigating and introducing novel targeted agents into clinical practice, with the aim of improving prognosis and quality of life. Angiogenesis is a possible target. The aim of this review is to investigate the most common molecular pathways of angiogenesis, which have provided novel targets for tailored therapy in patients with ovarian cancer. These therapeutic strategies include monoclonal antibodies and tyrosine-kinase inhibitors. These drugs have as molecular targets vascular endothelial growth factor, vascular endothelial growth factor receptors, platelet-derived growth factor, fibroblast growth factor, and angiopoietin. Bevacizumab was investigated in several Phase III studies, with interesting results. Today, there is strong evidence for introducing bevacizumab in the treatment of patients with advanced and recurrent ovarian cancer. Nevertheless, further investigations and large clinical trials are needed to understand the safety and effectiveness of bevacizumab, the optimal duration and timing of treatment, and activity in association with other chemotherapeutic and targeted agents. It also is necessary to identify biologic factors predictive of efficacy to choose the most appropriate antiangiogenic agent in the integrated treatment of epithelial ovarian cancer.Keywords: epithelial ovarian cancer, angiogenesis, bevacizumab, vascular endothelial growth factor, chemotherapy

  16. Loss of SerpinA5 protein expression is associated with advanced-stage serous ovarian tumors

    NARCIS (Netherlands)

    Bijsmans, Ingrid T. G. W.; Smits, Kim M.; de Graeff, Pauline; Wisman, G. Bea A.; van der Zee, Ate G. J.; Slangen, Brigitte F.; de Bruine, Adriaan P.; van Engeland, Manon; Sieben, Nathalie L.; Van de Vijver, Koen K.

    2011-01-01

    Epithelial ovarian cancer, the most lethal neoplasm of the female genital tract, is usually diagnosed at an advanced stage as obvious symptoms are absent at early stages. This disease is believed to originate from malignant transformation of the ovarian surface epithelium or fallopian tube. Histolog

  17. Expressions of Beta-catenin,E-cadherin and MMP-7 in Ovarian Epithelial Tumors

    Institute of Scientific and Technical Information of China (English)

    LIN Xiao; LI Yu; MI Can

    2008-01-01

    Objective:To investigate the expressions of Beta-catenin,E-cadherin and MMP-7 and their implications in ovarian epithelial tumor.Methods:lmmunohistochemicai staining with SP method was conducted to identify the expressions of Beta-catenin,E-cadherin and MMP-7 in ovarian epithelial tumor in 66 cases.Results:The abnormal expression rate of Beta-catenin in malignant ovarian epithelial tumor was higher than those in borderline and benign epithelial tumors(P<0.05).The positive rates of E-cadherin in benign and borderline ovarian epithelial tumors were significantly greater than that in malignant epithelial tumor.The expression rates of MMP-7 in malignant and borderline ovarian epithelial tumors were higher than that in benign epithelial tumor(P<0.05).Conclusion:The abnormal expressions of Beta-catenin,E-cadherin and MMP-7 might be used to indicate the malignance transform of ovarian epithelial tumors,but they have no significant correlation with peritoneal dropsy invasion,caul invasion and appendant invasion in ovarian epithelial tumor.

  18. Circulating Vitamin D and Risk of Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Alan A. Arslan

    2009-01-01

    Full Text Available We conducted a nested case-control study within two prospective cohorts, the New York University Women's Health Study and the Northern Sweden Health and Disease Study, to examine the association between prediagnostic circulating levels of 25-hydroxy vitamin D (25(OHD and the risk of subsequent invasive epithelial ovarian cancer (EOC. The 25(OHD levels were measured in serum or plasma from 170 incident cases of EOC and 373 matched controls. Overall, circulating 25(OHD levels were not associated with the risk of EOC in combined cohort analysis: adjusted OR for the top tertile versus the reference tertile, 1.09 (95% CI, 0.59–2.01. In addition, there was no evidence of an interaction effect between VDR SNP genotype or haplotype and circulating 25(OHD levels in relation to ovarian cancer risk, although more complex gene-environment interactions may exist.

  19. Epithelial ovarian carcinoma in women aged below 30 years

    Institute of Scientific and Technical Information of China (English)

    Chen Rong; Shen Keng; Wu Ming; Pan Ling-ya; Huang Hui-fang; Yang Jia-xin; Lang Jing-he

    2005-01-01

    Objective: To study the manifestation, pathohistologic type, stage of disease, treatment and outcome of epithelial ovarian carcinoma in women under the age of 30 years.Methods: The 21 cases of epithelial ovarian carcinoma in women aged below 30 years between Jan, 1986 and Mar, 2002 were analyzed retrospectively.Results: The median age at the time of diagnosis was 24 years (range, 16-29 years). All carcinomas occurred after menarche. The most common symptoms were abdominal pain (50%), followed by tympanites (25%) and menstrual disorders (19%). The initial diagnosis was usually made by physical examination, ultrasonography and serum CA125. The mean maximal tumor diameter was 17.6 cm. Ten patients had Stage I disease (5 Ia, 5 Ic), five had Stage Ⅲ disease, and the other six were unknown during staging operation. There were nine mucinous tumors, six serous tumors. Most tumors were well-differentiated and classified as Grade1 in 11 cases, Grade2 in 2 cases, Grade3 in 2 cases, unknown in 6 cases. Optimal and suboptimal cytoreduction was achieved in 14 patients in primary treatment and 5 in recurrent treatment. 8 patients were treated with conservative surgery. 18 patients were treated with chemotherapy and 7 patients had experienced six or more than six courses of chemotherapy. The median follow-up was 50 months (range, 2-192 months). There were 6 deaths, 2 alive with tumor, 11 alive without the disease, 2 losing follow-up. The 3-year survival rate was 89%, and 5-year survival rate was 76%.Conclusion: Young patients with epithelial ovarian carcinoma appeared to have a less aggressive form of the disease and a more favorable prognosis.

  20. YY1 modulates taxane response in epithelial ovarian cancer

    Energy Technology Data Exchange (ETDEWEB)

    Matsumura, Noriomi; Huang, Zhiqing; Baba, Tsukasa; Lee, Paula S.; Barnett, Jason C.; Mori, Seiichi; Chang, Jeffrey T.; Kuo, Wen-Lin; Gusberg, Alison H.; Whitaker, Regina S.; Gray, JoeW.; Fujii, Shingo; Berchuck, Andrew; Murphy, Susan K.

    2008-10-10

    The results of this study show that a high YY1 gene signature (characterized by coordinate elevated expression of transcription factor YY1 and putative YY1 target genes) within serous epithelial ovarian cancers is associated with enhanced response to taxane-based chemotherapy and improved survival. If confirmed in a prospective study, these results have important implications for the potential future use of individualized therapy in treating patients with ovarian cancer. Identification of the YY1 gene signature profile within a tumor prior to initiation of chemotherapy may provide valuable information about the anticipated response of these tumors to taxane-based drugs, leading to better informed decisions regarding chemotherapeutic choice. Survival of ovarian cancer patients is largely dictated by their response to chemotherapy, which depends on underlying molecular features of the malignancy. We previously identified YIN YANG 1 (YY1) as a gene whose expression is positively correlated with ovarian cancer survival. Herein we investigated the mechanistic basis of this association. Epigenetic and genetic characteristics of YY1 in serous epithelial ovarian cancer (SEOC) were analyzed along with YY1 mRNA and protein. Patterns of gene expression in primary SEOC and in the NCI60 database were investigated using computational methods. YY1 function and modulation of chemotherapeutic response in vitro was studied using siRNA knockdown. Microarray analysis showed strong positive correlation between expression of YY1 and genes with YY1 and transcription factor E2F binding motifs in SEOC and in the NCI60 cancer cell lines. Clustering of microarray data for these genes revealed that high YY1/E2F3 activity positively correlates with survival of patients treated with the microtubule stabilizing drug paclitaxel. Increased sensitivity to taxanes, but not to DNA crosslinking platinum agents, was also characteristic of NCI60 cancer cell lines with a high YY1/E2F signature. YY1

  1. The ascites N-glycome of epithelial ovarian cancer patients.

    Science.gov (United States)

    Biskup, Karina; Braicu, Elena I; Sehouli, Jalid; Tauber, Rudolf; Blanchard, Véronique

    2017-03-22

    Epithelial ovarian cancer (EOC) is worldwide the sixth most lethal form of cancer occurring in women. More than one third of ovarian patients have ascites at the time of diagnosis and almost all of them have it when recurrence occurs. Although its effect on tumor cell microenvironment remains poorly understood, its presence is correlated with bad diagnosis. In previous studies, we proposed a novel glycan-based biomarker for the diagnosis of EOC, which showed an improved sensitivity and specificity at any stage of the disease and an improved discrimination between malignant and benign ovarian tumors. In this work, we report for the first time the N-glycome profiles of ascitic fluid from primary serous EOC patients and compare them with the serum N-glycomes of the same patients as well as of healthy controls. N-Glycans were digested from equivalent amount of ascites and serum from 18 EOC patients and from serum of 20 age-matched controls and measured by MALDI-TOF-MS. Ascites N-glycome showed increased antennarity, branching, sialylation and Lewis(X) motives compared to healthy serum. In addition, a correlation was established between ascites volume and degree of sialylation.

  2. Up-Regulated FASN Expression Promotes Transcoelomic Metastasis of Ovarian Cancer Cell through Epithelial-Mesenchymal Transition

    Directory of Open Access Journals (Sweden)

    Li Jiang

    2014-06-01

    Full Text Available Fatty acid synthase (FASN, responsible for the de novo synthesis of fatty acids, has been shown to act as an oncogene in various human cancers. However, the mechanisms by which FASN favors the progression of ovarian carcinoma remain unknown. In this study, we evaluated FASN expression in ovarian cancer and investigated how FASN regulates the aggressiveness of ovarian cancer cells. Our results show that increased FASN is associated with the peritoneal metastasis of ovarian cancers. Over-expression of FASN results in a significant increase of tumor burden in peritoneal dissemination, accompanied by augment in cellular colony formation and metastatic ability. Correspondingly, FASN knockdown using RNA interference in ovarian cancer cells inhibits the migration in vitro and experimental peritoneal dissemination in vivo. Mechanistic studies reveal that FASN promotes Epithelial-mesenchymal Transition (EMT via a transcriptional regulation of E-cadherin and N-cadherin, which is also confirmed by luciferase promoter activity analysis. Taken together, our work demonstrates that FASN promotes the peritoneal dissemination of ovarian cancer cells, at least in part through the induction of EMT. These findings suggest that FASN plays a critical role in the peritoneal metastasis of ovarian cancer. Targeting de novo lipogenesis may have a therapeutic potential for advanced ovarian cancer.

  3. Nomogram for Suboptimal Cytoreduction at Primary Surgery for Advanced Stage Ovarian Cancer

    NARCIS (Netherlands)

    Gerestein, Cornelis G.; Eijkemans, Marinus J.; Bakker, Jeanette; Elgersma, Otto E.; Van der Burg, Maria E. L.; Kooi, Geertruida S.; Burger, Curt W.

    2011-01-01

    Aim: Maximal cytoreduction to minimal residual tumor is the most important determinant of prognosis in patients with advanced stage epithelial ovarian cancer (EOC). Preoperative prediction of suboptimal cytoreduction, defined as residual tumor >1 cm, could guide treatment decisions and improve couns

  4. Polymorphisms in stromal genes and susceptibility to serous epithelial ovarian cancer: a report from the Ovarian Cancer Association Consortium

    DEFF Research Database (Denmark)

    Amankwah, Ernest K; Wang, Qinggang; Schildkraut, Joellen M

    2011-01-01

    Alterations in stromal tissue components can inhibit or promote epithelial tumorigenesis. Decorin (DCN) and lumican (LUM) show reduced stromal expression in serous epithelial ovarian cancer (sEOC). We hypothesized that common variants in these genes associate with risk. Associations with sEOC amo...

  5. Polymorphisms in stromal genes and susceptibility to serous epithelial ovarian cancer: a report from the Ovarian Cancer Association Consortium

    DEFF Research Database (Denmark)

    Amankwah, Ernest K; Wang, Qinggang; Schildkraut, Joellen M

    2011-01-01

    Alterations in stromal tissue components can inhibit or promote epithelial tumorigenesis. Decorin (DCN) and lumican (LUM) show reduced stromal expression in serous epithelial ovarian cancer (sEOC). We hypothesized that common variants in these genes associate with risk. Associations with sEOC among...

  6. Expression of MTA2 Gene in Ovarian Epithelial Cancer and Its Clinical Implication

    Institute of Scientific and Technical Information of China (English)

    JI Yuxin; ZHANG Ping; LU Yunping; MA Ding

    2006-01-01

    In order to investigate the roles of MTA2 in the pathogenesis of ovarian epithelial cancer, the expression of MTA2 in 4 ovarian cell lines were detected by semi-quantitative RT-PCR and Western-blot assays. MTA2 expression in normal, borderline, benign and malignant epithelial o varian tissues was immunohistochemically examined. The expression of MTA2 mRNA and protein was detected in all of 4 cell lines of ovarian epithelial cancer. The expression of MTA2 mRNA and protein was higher in strong migration cell lines than in weak migration ones. In borderline and malignant ovarian tissues tested, MTA2 staining was dramatically stronger than in normal and benign tissues (P<0.01). The expression levels in malignant ovarian tissues were significantly higher than that in borderline epithelial ovarian tissues (P<0.01). The expression of MTA2 was correlated with clinical stage, histopathological grade and lymph node metastasis. It was concluded that the high expression of MTA2 was associated with more aggressive behaviors of epithelial ovarian cancer. MTA2 provides a novel indicator of ovarian cancer.

  7. Is tissue CA125 expression in epithelial ovarian adenocarcinoma heterogenic?

    DEFF Research Database (Denmark)

    Sparholt, Morten H; Høgdall, Claus K; Nedergaard, Lotte

    2013-01-01

    To evaluate if heterogeneity of tissue cancer antigen 125 (CA125) expression is present in epithelial serous adenocarcinomas. Furthermore, to investigate whether there is a correlation between levels of CA125 tissue expression, serum level of CA125, stage, and grade. A total of 10 patients...... diagnosed with serous ovarian adenocarcinomas were included. Preoperative blood samples were collected to determine serum CA125 levels. Tumor tissue from primary surgery was collected and processed for immunohistochemical analyses. CA125 was expressed in varying degrees in tumor tissues from all patients....... Mean tissue CA125 expression for each patient ranged from 36% to 98%. Intrapatient variations in tissue expression ranged from 10% to 90% point. No significant correlations between levels of CA125 tissue expression, serum level of CA125, stage, and grade were found. We found that the tissue expression...

  8. GSTP1 expression and promoter methylation in epithelial ovarian carcinoma

    Directory of Open Access Journals (Sweden)

    V Shilpa

    2014-01-01

    Full Text Available Context: GSTP1 is a subgroup of glutathione-S-transferase family, which provides cellular protection against free radical and carcinogenic compounds due to its detoxifying function. Altered GSTP1 activity due to down regulation of enzyme activity and DNA methylation has been reported in many tumors, although data for ovarian cancer are few. In this study, we aimed at determining the expression of GSTP1 in relation to the methylation of the GSTP1 promoter in epithelial ovarian cancer (EOC. Materials and Methods: GSTP1 mRNA expression and GSTP1 enzyme concentration were assessed by quantitative reverse transcriptase polymerase chain reaction (PCR and enzyme-linked immunosorbent assay, respectively, in 88 EOCs, 14 low malignant potential (LMP tumors, and 20 benign tumors. The promoter methylation of GSTP1 gene was evaluated by methylation-specific PCR. Results: Reduced GSTP1 mRNA expression was observed in 49% EOCs, 21.4% LMP, and 45% benign tumors. Significantly lower levels of plasma GSTP1 were observed in all tumor samples compared to normal. GSTP1 promoter methylation was detected in 10 (11.4% EOCs and 1 (7.3% LMP tumors. No methylation was observed in benign tumors and normal ovaries. Conclusions: Our results show that there is a significant down regulation of GSTP1 expression while hypermethylation of the GSTP1 gene promoter is not very frequent in EOC. Further studies are needed to study underlying mechanisms leading to decreased expression.

  9. Mitochondrial DNA sequence variants in epithelial ovarian tumor subtypes and stages

    Directory of Open Access Journals (Sweden)

    Aikhionbare Felix O

    2007-01-01

    Full Text Available Abstract Background A majority of primary ovarian neoplasms arise from cell surface epithelium of the ovaries. Although old age and a positive family history are associated risk factors, the etiology of the epithelial ovarian tumors is not completely understood. Additionally, knowledge of factors involved in the histogenesis of the various subtypes of this tumor as well as those factors that promote progression to advanced stages of ovarian malignancy are largely unknown. Current evidence suggests that mitochondrial alterations involved in cellular signaling pathways may be associated with tumorigenesis. Methods In this study, we determined the presence of polymorphisms and other sequence variants of mitochondrial DNA (mtDNA in 102 epithelial ovarian tumors including 10 matched normal tissues that paired with some of the tumors. High-resolution restriction endonucleases and PCR-based sequencing were used to assess the mtDNA variants spanning 3.3 kb fragment that comprised the D-Loop and 12S rRNA-tRNAphe, tRNAval, tRNAser, tRNAasp, tRNAlys, ATPase 6, ATPase 8, cytochrome oxidase I and II genes. Results Three hundred and fifty-two (352 mtDNA sequence variants were identified, of which 238 of 352 (68% have not been previously reported. There were relatively high frequencies of three mutations in the 12S rRNA gene at np 772, 773, and 780 in stage IIIC endometrioid tumors, two of which are novel (773delT and 780delC, and occurred with a frequency of 100% (7/7. Furthermore, two mutations were observed in serous tumors only at np 1657 in stage IV (10/10, and at np 8221delA in benign cystadenomas (3/3 and borderline tumors (4/4. A high frequency, 81% (13/16 of TC insertion at np 310 was found only in early stages of serous subtype (benign cystadenomas, 3/3; borderline tumors, 4/4; stage I tumors, 2/5 and matched normal tissues 4/4. Conclusion Our findings indicate that certain mtDNA mutations can reliably distinguish the different histologic subtypes of

  10. ATM, ATR and DNA-PKcs expressions correlate to adverse clinical outcomes in epithelial ovarian cancers

    Science.gov (United States)

    Abdel-Fatah, Tarek M.A.; Arora, Arvind; Moseley, Paul; Coveney, Clare; Perry, Christina; Johnson, Kerstie; Kent, Christopher; Ball, Graham; Chan, Stephen; Madhusudan, Srinivasan

    2014-01-01

    Background Ataxia-telangiectasia mutated (ATM), ataxia-telangiectasia mutated and rad3 related (ATR) and DNA-dependent protein kinase catalytic sub-unit (DNA-PKcs) play critical roles in DNA damage response (DDR) by linking DNA damage sensing to DDR effectors that regulate cell cycle progression and DNA repair. Our objective was to evaluate if ATM, ATR and DNA-PKcs expressions could predict response to therapy and clinical outcome in epithelial ovarian cancers. Methods We investigated ATM, ATR, and DNA-PKcs expressions in ovarian epithelial cancers [protein expression (n = 194 patients), mRNA expression (n = 156 patients)] and correlated to clinicopathological outcomes as well as expression of X-ray repair cross-complementing protein 1 (XRCC1), cell division cycle-45 (CDC45), cyclin-dependent kinase 1(CDK1) and Ki-67 in tumours. Results High ATM protein expression was associated with serous cystadenocarcinomas (p = 0.021) and platinum resistance (p = 0.017). High DNA-PKcs protein expression was associated with serous cystadenocarcinomas (p = 0.006) and advanced stage tumours (p = 0.018). High ATM protein (p = 0.001), high ATM mRNA (p = 0.018), high DNA-PKcs protein (p = 0.002), high DNA-PKcs mRNA (p = 0.044) and high ATR protein (p = 0.001) expressions are correlated with poor ovarian cancer specific survival (OCSS). In multivariate Cox model, high DNA-PKcs (p = 0.006) and high ATR (p = 0.043) protein expressions remain independently associated with poor OCSS. Conclusions ATM, ATR and DNA-PKcs expressions may have prognostic and predictive significances in epithelial ovarian cancer. General significance The data presented here provides evidence that ATM, ATR and DNA-PKcs involved in DDR are not only promising biomarkers but are also rational targets for personalized therapy in ovarian cancer. PMID:26674120

  11. NANOG regulates epithelial-mesenchymal transition and chemoresistance through activation of the STAT3 pathway in epithelial ovarian cancer.

    Science.gov (United States)

    Liu, Suqing; Sun, Jing; Cai, Bin; Xi, Xiaowei; Yang, Liu; Zhang, Zhenbo; Feng, Youji; Sun, Yunyan

    2016-07-01

    NANOG is a key transcription factor that is overexpressed and plays an important role in various cancers. Its overexpression is associated with highly tumorigenic, drug-resistant, and poor prognosis. However, the underlying mechanism of action of NANOG in ovarian cancer remains unclear. Epithelial-mesenchymal transition (EMT), which is a critical process in cancer invasion and metastasis, is also associated with drug resistance. We determined whether NANOG is associated with EMT and chemoresistance in epithelial ovarian cancer cells. NANOG expression was increased in epithelial ovarian cancer cells (HEY and SKOV3) compared with normal epithelial ovarian cells (Moody). Low expression of NANOG increased the expression of E-cadherin and decreased the expression of vimentin, β-catenin, and Snail. Furthermore, the cell migration and invasion abilities were decreased. The multidrug resistance genes MDR-1 and GST-π were also downregulated when NANOG was lowly expressed. The cells that were transfected with the si-NANOG plasmid were more sensitive to cisplatin compared with the cells that were transfected with empty vector. The data demonstrated that Stat3 was correlated with NANOG-mediated EMT and drug resistance. The silencing of Stat3 expression abrogated NANOG-mediated EMT changes and increased the sensitivity of the cells to chemotherapy. These results suggest that NANOG mediates EMT and drug resistance through activation of the Stat3 pathway in epithelial ovarian cancer.

  12. High prevalence of atypical hyperplasia in the endometrium of patients with epithelial ovarian cancer

    NARCIS (Netherlands)

    Mingels, M.J.J.M.; Masadah, R.; Geels, Y.P.; Otte-Holler, I.; Kievit, I.M. de; Laak, J.A.W.M. van der; Ham, M.A.P.C. van; Bulten, J.; Massuger, L.F.A.G.

    2014-01-01

    OBJECTIVES: The aim of the present study is to determine the prevalence of endometrial premalignancies in women diagnosed with epithelial ovarian cancer (EOC). METHODS: Endometrial and ovarian specimens of 186 patients with EOC were retrospectively selected using the nationwide pathology network and

  13. Epithelial ovarian cancer and the occurrence of skin cancer in the Netherlands: histological type connotations

    NARCIS (Netherlands)

    Niekerk, G.C. van; Bulten, J.; Verbeek, A.L.M.

    2011-01-01

    Background. Patients with epithelial ovarian cancer have a high risk of (non-)melanoma skin cancer. The association between histological variants of primary ovarian cancer and skin cancer is poorly documented. Objectives. To further evaluate the risk of skin cancer based on the histology of the epit

  14. The Serum Glycome to Discriminate between Early-Stage Epithelial Ovarian Cancer and Benign Ovarian Diseases

    Directory of Open Access Journals (Sweden)

    Karina Biskup

    2014-01-01

    Full Text Available Epithelial ovarian cancer (EOC is the sixth most common cause of cancer deaths in women because the diagnosis occurs mostly when the disease is in its late-stage. Current diagnostic methods of EOC show only a moderate sensitivity, especially at an early-stage of the disease; hence, novel biomarkers are needed to improve the diagnosis. We recently reported that serum glycome modifications observed in late-stage EOC patients by MALDI-TOF-MS could be combined as a glycan score named GLYCOV that was calculated from the relative areas of the 11 N-glycan structures that were significantly modulated. Here, we evaluated the ability of GLYCOV to recognize early-stage EOC in a cohort of 73 individuals comprised of 20 early-stage primary serous EOC, 20 benign ovarian diseases (BOD, and 33 age-matched healthy controls. GLYCOV was able to recognize stage I EOC whereas CA125 values were statistically significant only for stage II EOC patients. In addition, GLYCOV was more sensitive and specific compared to CA125 in distinguishing early-stage EOC from BOD patients, which is of high relevance to clinicians as it is difficult for them to diagnose malignancy prior to operation.

  15. Medical therapy of advanced malignant epithelial tumours of the ovary.

    Science.gov (United States)

    Colombo, N; Parma, G; Bocciolone, L; Franchi, D; Sideri, M; Maggioni, A

    2000-01-01

    Despite improvements seen in median and overall survival using a combination of platinum-compounds and paclitaxel (PTX), long-term survival rates for patients with advanced epithelial ovarian carcinoma remain disappointing and ongoing efforts have aimed to develop more effective primary therapy. In the early 1990Os the drug PTX was first tested in ovarian cancer. In the Gynaecological Oncology Group (GOG) trial 111 the cisplatin (CP)+PTX regimen was judged to be superior compared to the platinum-based control arm with an improvement of overall response rate, median progression-free interval and overall median survival. These favourable data were confirmed by a European-Canadian Intergroup trial (OV10). In contrast, in a further GOG trial (GOG132) there was no difference in survival between CP alone and the combination of PTX and CP. The International Collaborative Ovarian Neoplasm Study (ICON)3 is the first and only trial comparing PTX plus carboplatin against carboplatin alone or a (non-taxane) CP-based control arm. The last analysis performed with a total of 1,293 events showed an estimated absolute difference in one-year progression-free survival of 1% and in two-year overall survival of 2% both in favour of PTX plus carboplatin. The results of ICON3, in accordance with GOG132 study, appear to contradict the earlier positive results seen for PTX and CP in the GOG-111 and OV10 trials and suggested that single agent carboplatin, CY-adriamycin-CP are safe and effective first-line treatments for women requiring chemotherapy for ovarian cancer. A meta-analysis with individual patient data is warranted to better clarify the issue of PTX in the front line therapy of advanced ovarian cancer. Salvage chemotherapy is often utilised in patients with advanced ovarian cancer, due to the high frequency of recurrent disease even after a clinical or pathological complete response after primary chemotherapy. Main objectives of salvage chemotherapy include: i. improvement in

  16. mRNA EXPRESSION OF PTEN AND VEGF GENES IN EPITHELIAL OVARIAN CANCER

    Institute of Scientific and Technical Information of China (English)

    陈颖; 赵雨杰; 郑华川; 杨雪飞; 汪桂兰; 辛彦

    2003-01-01

    Objective: To investigate the mRNA expression of PTEN and vascular endothelial growth factor (VEGF) genes in ovarian cancer. Methods:We examined mRNA expression of PTEN and VEGF165 in normal ovary (n=5), ovarian cyst (n=5), ovarian borderline tumor (n=9), epithelial ovarian cancer (n=60) and ovarian cancer cell line (CAOV-3) by RT-PCR. Their expressions were compared with clinicopathological features of ovarian cancer. The relationship between their expressions was concerned in all ovarian samples as well. Results:mRNA expression level of PTEN gene was significantly lower in ovarian borderline tumor or ovarian cancer than that in normal ovary or ovarian cyst(P<0.05). It was negatively correlated with clinicopathological staging(P<0.05),whereas positively with histological differentiation (P<0.05). mRNA expression level of PTEN gene was significantly lower in ovarian endometrioid cancer than ovarian serous or mucinous cancer(P<0.05). mRNA expression level of VEGF165 gene was significantly higher in ovarian cancer than that in normal ovary or ovarian cyst(P<0.05). It was positively correlated with clinicopathological staging(P<0.05), whereas negatively with histological differentiation (P<0.05). mRNA expression level of VEGF165 gene was significantly higher in ovarian serous cancer than in other ovarian epithelial cancers (P<0.05). mRNA expression of VEGF165 gene was inversely correlated with mRNA expression level of PTEN gene. Conclusion:Down-regulated expression of PTEN and up-regulated expression of VEGF were considered as two important events in tumorigenesis of ovarian cancer and could be used as molecular markers to indicate the pathobiological behaviors of ovarian cancer. Decreased PTEN expression and increased VEGF expression were closely associated with tumorigenesis and pathobiological behaviors of ovarian endometrioid and serous cancer respectively. Reduced expression of PTEN gene might be involved in carcinogenesis and progression of ovarian cancer by

  17. Microcell-mediated chromosome transfer identifies EPB41L3 as a functional suppressor of epithelial ovarian cancers

    DEFF Research Database (Denmark)

    Dafou, Dimitra; Grun, Barbara; Sinclair, John

    2010-01-01

    lines. Using immunohistochemistry, 66% of 794 invasive ovarian tumors showed no EPB41L3 expression compared with only 24% of benign ovarian tumors and 0% of normal ovarian epithelial tissues. EPB41L3 was extensively methylated in ovarian cancer cell lines and primary ovarian tumors compared with normal...... (erythrocyte membrane protein band 4.1-like 3, alternative names DAL-1 and 4.1B) was a candidate ovarian cancer-suppressor gene. Immunoblot analysis showed that EPB41L3 was activated in TOV21G(+18) hybrids, expressed in normal ovarian epithelial cell lines, but was absent in 15 (78%) of 19 ovarian cancer cell...... tissues (P = .00004), suggesting this may be the mechanism of gene inactivation in ovarian cancers. Constitutive reexpression of EPB41L3 in a three-dimensional multicellular spheroid model of ovarian cancer caused significant growth suppression and induced apoptosis. Transmission and scanning electron...

  18. Epithelial ovarian tumors: Clinicopathological correlation and immunohistochemical study

    Directory of Open Access Journals (Sweden)

    Pooja S Naik

    2015-01-01

    Full Text Available Background: Ovarian cancer is the third leading site of cancer among women, trailing behind cervix and breast cancer. Aim: This study was undertaken to analyze the immunohistochemical (IHC profile of estrogen receptors (ER, progesterone receptors (PR, Ki-67, and p53 in various ovarian epithelial tumors and attempt correlation with clinical and histopathological findings. Materials and Methods: The present study was conducted over a period of 4 years. A technique of manual tissue array was employed for cases subjected for IHC. The primary antibodies used were ER, PR, p53, and Ki-67. A correlation was attempted between histopathological and IHC findings. Results were subjected to statistical analysis. Software program "the primer of biostatistics 5.0" was used for calculation of interrelationships between the analyzed ER, PR, p53, and Ki-67 expression and histological factors by Pearson′s Chi-square test. The results were considered to be significant when the P < 0.05. Results: There were 110 cases of surface epithelial ovarian tumors (SEOT encountered over the period of 4 years. The expression of ER was more in malignant tumors (13/16, 81.25% than borderline (9/12, 75% and benign (20/82, 24.39%. As compared to ER, the expression of PR was more in benign (51/82, 62.19% than borderline (8/12, 66.67% and malignant tumors (9/16, 56.25%. The expression of PR was more in benign tumors than borderline and malignant tumors. However, this was not statistically significant (Chi-square = 0.335 with 2 degrees of freedom; P = 0.846. The expression of p53 was less in benign (5/82, 6.1% than borderline (9/12, 75% and malignant tumors (13/16, 81.25%. The expression of Ki-67 was more in malignant (4/82, 4.88% than borderline (10/12, 83.33% and benign tumors (15/16, 93.75%. In all the above cases, the difference was statistically significant (P < 0.05. There was statistically significant difference in the expression of ER, PR, p53, and Ki-67 in the patients with

  19. Effect of retroperitoneal lymphadenectomy on prognosis of patients with epithelial ovarian cancer

    Institute of Scientific and Technical Information of China (English)

    王泽华; 熊宙芳; 王世宣

    2003-01-01

    Objective To evaluate prognostic factors which have an influence on overall survival and to assess the rational application of retroperitoneal lymphadenectomy in patients with epithelial ovarian cancer. Methods The data of 131 patients treated between January 1990 and December 1998 in Union Hospital and Tongji Hospital were analyzed retrospectively. Survival was calculated using the Kaplan-Meier method and comparisons were performed using Log-rank test. Independent prognostic factors were identified by the Cox proportional hazards regression model. Results Univariate analysis showed that age, general conditions, menopausal status, stage, pathological types, location of the tumor, residual tumor and retroperitoneal lymphadenectomy were prognostic factors. Multivariate analysis showed that age, stage, residual tumor, retroperitoneal lymphadenectomy and the number of courses of chemotherapy were the most important prognostic factors. The survival rate could not be improved through retroperitoneal lymphadenectomy in the patients in early stage, advanced stage with residual tumor >2 cm or those with mucinous adenocarcinoma (P>0.05). Among patients in advanced stage cancer with a residual tumor ≤2 cm, 5-year survival was 65% and 30% for patients who did and did not undergo lymphadenectomy, respectively (P<0.01). Among patients with serous adenocarcinoma, 5-year survival was 61% and 31% for patients who did and did not undergo lymphadenectomy, respectively (P<0.01). Conclusions The prognosis of the patients with epithelial ovarian cancer may be influenced by age, stage, residual tumor, retroperitoneal lymphadenectomy and the number of courses of chemotherapy. Although retroperitoneal lymphadenectomy could improve the survival rate, it should be carried out selectively.

  20. A case-control study of risk factors for epithelial ovarian cancer

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    Ghaem Maghami Noori F

    2001-09-01

    Full Text Available Ovarian cancer is second prevalent cancer among gynecologic malignancies and the most common type of ovarian cancer is epithelial form (85-90 percent. To detect the risk factors for the epithelial ovarian cancer, a case-control study was conducted in Valieasr hospital in 1988. In this study, 118 cases with epithelial ovarian cancer (according histological records and 240 controls without any gynecological cancer in gynecologic clinic had been interviewed. For data analysis, T-test, Chi2 test and logistic regression have been used at a =0.05 as level of significance. The mean age in cases was 50±13 and in controls was 49.9±12 years, without significant different. The mean number of pregnancies and parity in cases was less than controls, significantly (P<0.03. The mean months of breast feeding in cases was less than controls (54.9±71.2 versus 82.4±62.7 (P<0.001. The cases had a lower mean age of menarch than controls (P=0.03. 58 percent of cases and 21.3 percent of controls hadn't used any contraception methods (P=0.00001. The mean years of contraception was significantly less in cases versus controls (P<0.001. The odds ratio for epithelial ovarian cancer was 0.24 (95 percent CI: 0.13-0.48 in OCP users, 0.47 (95 percent CI: 0.005-0.43 in TL method, and was 0.41 (95 percent CI: 0.22-0.76 in other contraception methods, relative to women who hadn't used any contraception methods. This study reveals that epithelial ovarian cancer risk increases significantly with earlier menarch, decreasing number of pregnancy, deliveries duration of breast feeding and use of contraception methods. Use of contraception pill and tubal ligation method decreases risk of epithelial ovarian cancer.

  1. Re-evaluation of interval debulking surgery in advanced epithelial ovarian cancer%间歇性肿瘤细胞减灭术治疗晚期卵巢上皮性癌的再评价

    Institute of Scientific and Technical Information of China (English)

    马彧; 李艺; 崔恒; 梁旭东; 唐志坚; 李小平; 赵彦; 魏丽惠

    2012-01-01

    Objective Previous study showed that interval debulking surgery (IDS) may improve the survival of patients with advanced epithelial ovarian cancer (EOC).The precise significance of IDS needs to be evaluated.Methods Totally 136 consecutive patients with stage Ⅲ c or Ⅳ EOC (including primary peritoneal carcinoma and primary fallopian tube carcinoma ) who completed primary debulking surgery (PDS) and platinum-based chemotherapy were enrolled from January 2000 to December 2009 in a retrospective cohort study.The study group was divided into three groups:65 cases underwent optimal PDS (Group A ),41 cases received chemotherapy alone after suboptimal PDS (Group B ),and 30 patients underwent IDS after suboptimal PDS (Group C).All patients received six to eight courses of platinum-based combination chemotherapy (paclitaxel plus carboplatin/cisplatin,cyclophosphamide plus epirubicin and cisplatin).Patients' clinical characteristics,perioperative situation and prognosis were compared. Results Sixty-five cases (47.8%,65/136) from 136 patients achieved optimal PDS.For Group C,77% (23/30)patients obtained optimal debulking surgery after IDS.Intraoperative injury rates were similar between Group B and Group C ( P > 0.05 ).Mild perioperative complications rate was also similar ( P >0.05 ).Median progression-free survival (PFS) of Group A was 26 months.Median overall survival (OS) of Group B and Group C were 3l months and 40 months,respectively (P =0.254).Median PFS of Group B and Group C were 13 months and 24 months,respectively (P =0.289).Although when it came to 20 months after PDS,patients who underwent IDS had a significantly lower progressive disease (PD) rate (Group B 33% versus Group C 61%,P =0.046 ),it still showed that there was no significant difference in either OS or PFS of these two groups.Those patients in Group C who obtained no visible residual got similar PFS (27 months) comparing to Group A (26 months,P =0.730),but OS was still shorter (P =0

  2. Expression of SDF-1 and CXCR4 transcript variants and CXCR7 in epithelial ovarian cancer.

    Science.gov (United States)

    Jaszczynska-Nowinka, Karolina; Rucinski, Marcin; Ziolkowska, Agnieszka; Markowska, Anna; Malendowicz, Ludwik K

    2014-05-01

    Chemokine stromal cell-derived factor-1 (SDF-1) and its receptors, CXCR4 and CXCR7, have been implicated in epithelial ovarian cancer progression and metastasis. However, limited data are available on the expression levels of SDF-1 and CXCR4 variants and CXCR7 in human epithelial ovarian cancer. The present study aimed to characterize the expression pattern and levels of SDF-1, CXCR4 and CXCR7 in normal human ovaries and epithelial ovarian cancer. The expression of SDF-1 and CXCR4 transcript variants and CXCR7 was determined by quantitative polymerase chain reaction (qPCR). Plasma SDF-1α levels were determined by commercially available EIA kits and cancer antigen 125 (CA 125) levels were quantified by automated microparticle enzyme immunosorbent assay. High expression levels of SDF-1 transcript variant 1 were identified in ovarian cancer and control ovaries. By contrast, in both groups the expression levels of SDF-1 transcript variants 3 and 4 were extremely low. Furthermore, SDF-1 variant 1 levels were notably higher in epithelial ovarian cancer than in control ovaries, while data for the remaining transcripts were similar in both groups. CXCR4 transcript variant 2 and CXCR7 expression levels in normal and neoplastic ovaries were similar. In both groups, CXCR4 transcript variant 2 was not detected. Plasma SDF-1α levels were notably higher in females with epithelial ovarian cancer than in the control ovaries. Elevated levels of blood SDF-1α were found prior to surgery, 6 days after surgery and following completion of the first chemotherapy course. These increases were independent of the type of epithelial ovarian cancer. Our results suggest that the expression of SDF-1 and the genes controlling alternative splicing are elevated in epithelial ovarian cancer, leading to an increased formation of SDF-1 variant 1. Elevated plasma SDF-1α levels in epithelial ovarian cancer patients are not associated with the presence of tumors and/or metastases, however reflect a

  3. Overexpression of human sperm protein 17 increases migration and decreases the chemosensitivity of human epithelial ovarian cancer cells

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    Huang Wen-bin

    2009-09-01

    Full Text Available Abstract Background Most deaths from ovarian cancer are due to metastases that are resistant to conventional therapies. But the factors that regulate the metastatic process and chemoresistance of ovarian cancer are poorly understood. In the current study, we investigated the aberrant expression of human sperm protein 17 (HSp17 in human epithelial ovarian cancer cells and tried to analyze its influences on the cell behaviors like migration and chemoresistance. Methods Immunohistochemistry and immunocytochemistry were used to identify HSp17 in paraffin embedded ovarian malignant tumor specimens and peritoneal metastatic malignant cells. Then we examined the effect of HSp17 overexpression on the proliferation, migration, and chemoresistance of ovarian cancer cells to carboplatin and cisplatin in a human ovarian carcinoma cell line, HO8910. Results We found that HSp17 was aberrantly expressed in 43% (30/70 of the patients with primary epithelial ovarian carcinomas, and in all of the metastatic cancer cells of ascites from 8 patients. The Sp17 expression was also detected in the metastatic lesions the same as in ovarian lesions. None of the 7 non-epithelial tumors primarily developed in the ovaries was immunopositive for HSp17. Overexpression of HSp17 increased the migration but decreased the chemosensitivity of ovarian carcinoma cells to carboplatin and cisplatin. Conclusion HSp17 is aberrantly expressed in a significant proportion of epithelial ovarian carcinomas. Our results strongly suggest that HSp17 plays a role in metastatic disease and resistance of epithelial ovarian carcinoma to chemotherapy.

  4. Expression of aFGF, bFGF, and FGFR1 in ovarian epithelial neoplasm

    Institute of Scientific and Technical Information of China (English)

    张颐; 郭科军; 尚海; 王亚军; 孙黎光

    2004-01-01

    @@ Ovarian epithelial cancer is a common malignant ovarian neoplasm with a high mortality. The factors that regulate the rapid growth of ovarian epithelial cancers are still largely unknown. There are some evidences indicating that oncogene can confer growth factor automatically onto cancer cells. The autocrine secretion hypothesis proposes that, as a result of oncogene activation, neoplastic cells can escape growth-restraining mechanism by independently producing and responding to their own growth factors. In recent years, attention has focused on fibroblast growth factor (FGF), as well as acidic fibroblast growth factor (aFGF) and basic fibroblast growth factor (bFGF), because it is a polypeptide growth factor with a widespread biological activity. In order to explore the factors responsible for the rapid growth and proliferation of human ovarian cancer, we investigated the possible role of aFGF and bFGF and their receptors (FGFR1).

  5. Enhanced efficacy and specificity of epithelial ovarian carcinogenesis by embedding a DMBA-coated cloth strip in the ovary of rat

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    Huang Yiping

    2012-09-01

    Full Text Available Abstract Background Ovarian cancer is predominant of epithelial cell origin and often present at an advanced stage with poor prognosis. Most animal models of ovarian carcinoma yield thecal/granulose cell tumors, rather than adenocarcinomas. The best reported induction rate of adenocarcinoma in rats is 10-45% by an ovarian implantation of 7, 12-dimethylbenz[a]anthracene (DMBA coated silk suture. We provided an improved procedure to construct the model by the ovarian implantation of DMBA-coated cloth strip. Methods A sterile suture (as S group or a piece of cloth strip (as CS group was soaked in DMBA before ovarian implantation in Wistar rats. Tumor size, incidence rate and pathological type were analyzed. Results Ovarian tumors in rats of CS group were first noted at 16 wk post implantation and reached a cumulative incidence of 75% (96/128 at 32 wk, while the tumor incidence rate in S group at 32 wk was only 46.25% (37/80. The tumor size in CS group (3.63 ± 0.89 cm was larger than that of S group (2.44 ± 1.89 cm (P  Conclusion The model in our study yields much higher incidence and specificity of epithelial derived tumors and showed histological similarities to human ovarian cancers, which would be more suitable for therapeutic research.

  6. Paraaortic node recurrence 25 years after removal of epithelial ovarian carcinoma.

    Science.gov (United States)

    Otsuka, Isao; Shoji, Kazufusa

    2016-11-01

    In epithelial ovarian carcinoma, very late (more than 20 years) recurrence is an unusual event. In patients experiencing such a recurrence, the effectiveness of platinum/taxane chemotherapy has been questioned. A 54-year old woman presented with paraaortic node swelling that appeared 25 years after treatment of stage I epithelial ovarian carcinoma. She underwent a partial resection of the nodes and histologic examination showed high-grade serous carcinoma. She received paclitaxel and carboplatin chemotherapy and a partial response was initially observed on imaging studies; however, serum cancer antigen125 levels increased thereafter. She received radiation therapy to the paraaortic nodal disease with doses of 45 Gy and achieved a complete response. She was disease-free more than eight years after the detection of recurrence. In conclusion, radiation therapy may be an effective treatment option in patients with very late recurrence of epithelial ovarian carcinoma refractory to platinum/taxane chemotherapy.

  7. Activin is a potent growth suppressor of epithelial ovarian cancer cells.

    Science.gov (United States)

    Ramachandran, Anassuya; Marshall, Elaine S; Love, Donald R; Baguley, Bruce C; Shelling, Andrew N

    2009-11-28

    Although activin is a major cytokine produced by the ovary, its role in epithelial ovarian cancer is poorly defined. Here, we demonstrate a novel role for activin as a growth inhibitor of some (8/16) epithelial ovarian cancer cell lines. Unresponsive cell lines displayed transcriptional downregulation of the activin receptors ACTRIIA and ACTRIB, suggesting resistance to activin signalling. In response to activin, growth inhibited cell lines demonstrated activation of the canonical SMAD2/3/4, transcriptional induction of the CDK inhibitor p15INK4B, suppression of C-MYC levels and a G1 phase cell cycle arrest. Thus, activin is a potent inhibitor of proliferation of some epithelial ovarian cancer cell lines and its role in the pathogenesis of this disease needs to be re-evaluated.

  8. Overexpression of Notch3 and pS6 Is Associated with Poor Prognosis in Human Ovarian Epithelial Cancer

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    Zhaoxia Liu

    2016-01-01

    Full Text Available Notch3 and pS6 play important roles in tumor angiogenesis. To assess the expression of Notch3 and pS6 in Chinese ovarian epithelial cancer patients, a ten-year follow-up study was performed in ovarian epithelial cancer tissues from 120 specimens of human ovarian epithelial cancer, 30 specimens from benign ovarian tumors, and 30 samples from healthy ovaries by immunohistochemistry. The results indicate that the expression of Notch3 and pS6 was higher in ovarian epithelial cancer than in normal ovary tissues and in benign ovarian tumor tissues (p0.05 but positively associated with clinical stage, pathological grading, histologic type, lymph node metastasis, and ascites (p<0.05 or p<0.01. A follow-up survey of 64 patients with ovarian epithelial cancer showed that patients with high Notch3 and pS6 expression had a shorter survival time (p<0.01, in which the clinical stage (p<0.05 and Notch3 expression (p<0.01 played important roles. In conclusion, Notch3 and pS6 are significantly related to ovarian epithelial cancer development and prognosis, and their combination represents a potential biomarker and therapeutic target in ovarian tumor angiogenesis.

  9. Survivorship Care Planning in Improving Quality of Life in Survivors of Ovarian Cancer

    Science.gov (United States)

    2017-02-19

    Cancer Survivor; Stage IA Ovarian Epithelial Cancer; Stage IB Ovarian Epithelial Cancer; Stage IC Ovarian Epithelial Cancer; Stage IIA Ovarian Epithelial Cancer; Stage IIB Ovarian Epithelial Cancer; Stage IIC Ovarian Epithelial Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIC Ovarian Epithelial Cancer

  10. The essential roles of CCR7 in epithelial-to-mesenchymal transition induced by hypoxia in epithelial ovarian carcinomas.

    Science.gov (United States)

    Cheng, Shaomei; Han, Lin; Guo, Jingyan; Yang, Qing; Zhou, Jianfang; Yang, Xiangshan

    2014-12-01

    The chemokine receptor CCR7 and its ligands CCL19/21 mediate the tumor mobility, invasion, and metastasis (Wu et al. Curr Pharm Des. 15:742-57, 2009). Hypoxia induced epithelial-to-mesenchymal transition (EMT) to facilitate the tumor biology. Here, we addressed the roles of CCR7 in epithelial ovarian carcinoma tissues and hypoxia-induced serous papillary cystic adenocarcinoma (SKOV-3) EMT. The expression level of CCR7 protein was analyzed by immunohistochemistry in 30 specimens of epithelial ovarian carcinomas. Western blot was used to investigate the expression of hypoxia-induced CCR7, HIF-1α, and EMT markers (N-cadherin, Snail, MMP-9). In addition, wound healing and Transwell assay were introduced to observe the capacity of migration and invasiveness. Our data showed CCR7 expression was observed in 22 cases of tissues and closely associated with lymph node metastasis and FIGO stage (III + IV). At 6, 12, 24, and 36 h following hypoxia, CCR7 and HIF-1α proteins were both obviously upregulated in a time-dependent method, compared with normal oxygen. In vitro, SKOV-3 expressed N-cadherin, Snail, and MMP-9 once either CCL21 stimulation or hypoxia induction, while hypoxia accompanied with CCL21 induction exhibited strongest upregulation of N-cadherin, Snail, and MMP-9 proteins. Besides, wound healing and Transwell assay further identified that hypoxia with CCL21 stimulation can remarkably promote cell migration and invasiveness. Taken together, CCR7 can constitutively express in epithelial ovarian carcinomas and be induced rapidly in response to hypoxia, which indeed participates in EMT development and prompts the cell migration and invasion. Thus, this study suggested that the epithelial ovarian cancer invasion and metastasis can be inhibited by antagonizing CCR7.

  11. Alisertib, an Aurora kinase A inhibitor, induces apoptosis and autophagy but inhibits epithelial to mesenchymal transition in human epithelial ovarian cancer cells

    Directory of Open Access Journals (Sweden)

    Ding YH

    2015-01-01

    Full Text Available Yong-Hui Ding,1,2 Zhi-Wei Zhou,2,3 Chun-Fang Ha,1 Xue-Yu Zhang,1 Shu-Ting Pan,4 Zhi-Xu He,3 Jeffrey L Edelman,2 Dong Wang,5 Yin-Xue Yang,6 Xueji Zhang,7 Wei Duan,8 Tianxin Yang,9 Jia-Xuan Qiu,4 Shu-Feng Zhou2,3 1Department of Gynecology, General Hospital of Ningxia Medical University, Yinchuan, People’s Republic of China; 2Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA ; 3Guizhou Provincial Key Laboratory for Regenerative Medicine, Stem Cell and Tissue Engineering Research Center and Sino-US Joint Laboratory for Medical Sciences, Guiyang Medical University, Guiyang, 4Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, 5Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, 6Department of Colorectal Surgery, General Hospital of Ningxia Medical University, Yinchuan, 7Research Center for Bioengineering and Sensing Technology, University of Science and Technology Beijing, Beijing, People’s Republic of China; 8School of Medicine, Deakin University, Waurn Ponds, Australia; 9Department of Internal Medicine, University of Utah and Salt Lake Veterans Affairs Medical Center, Salt Lake City, UT, USA Abstract: Ovarian cancer is a leading killer of women, and no cure for advanced ovarian cancer is available. Alisertib (ALS, a selective Aurora kinase A (AURKA inhibitor, has shown potent anticancer effects, and is under clinical investigation for the treatment of advanced solid tumor and hematologic malignancies. However, the role of ALS in the treatment of ovarian cancer remains unclear. This study investigated the effects of ALS on cell growth, apoptosis, autophagy, and epithelial to mesenchymal transition (EMT, and the underlying mechanisms in human epithelial ovarian cancer SKOV3 and OVCAR4 cells. Our docking study showed that ALS, MLN8054, and VX-680 preferentially bound to AURKA

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

    Institute of Scientific and Technical Information of China (English)

    蒋学锋; 朱涛; 杨洁; 李双; 叶双梅; 廖书杰; 孟力; 卢运萍; 马丁

    2010-01-01

    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 ...

  13. Stages of Ovarian Epithelial, Fallopian Tube, and Primary Peritoneal Cancer

    Science.gov (United States)

    ... peritoneal cancer include pain or swelling in the abdomen. Ovarian, fallopian tube, or peritoneal cancer may not ... swelling, or a feeling of pressure in the abdomen or pelvis. Vaginal bleeding that is heavy or ...

  14. Inflammatory Cytokine Tumor Necrosis Factor α Confers Precancerous Phenotype in an Organoid Model of Normal Human Ovarian Surface Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Joseph Kwong

    2009-06-01

    Full Text Available In this study, we established an in vitro organoid model of normal human ovarian surface epithelial (HOSE cells. The spheroids of these normal HOSE cells resembled epithelial inclusion cysts in human ovarian cortex, which are the cells of origin of ovarian epithelial tumor. Because there are strong correlations between chronic inflammation and the incidence of ovarian cancer, we used the organoid model to test whether protumor inflammatory cytokine tumor necrosis factor α would induce malignant phenotype in normal HOSE cells. Prolonged treatment of tumor necrosis factor α induced phenotypic changes of the HOSE spheroids, which exhibited the characteristics of precancerous lesions of ovarian epithelial tumors, including reinitiation of cell proliferation, structural disorganization, epithelial stratification, loss of epithelial polarity, degradation of basement membrane, cell invasion, and overexpression of ovarian cancer markers. The result of this study provides not only an evidence supporting the link between chronic inflammation and ovarian cancer formation but also a relevant and novel in vitro model for studying of early events of ovarian cancer.

  15. Clinical Practice of Adjuvant Chemotherapy in Patients with Early-Stage Epithelial Ovarian Cancer

    NARCIS (Netherlands)

    Frielink, L.M.; Pijlman, B.M.; Ezendam, N.P.; Pijnenborg, J.M.A.

    2016-01-01

    BACKGROUND: Adjuvant platinum-based chemotherapy improves survival in women with early-stage epithelial ovarian cancer (EOC). Yet, there is a wide variety in clinical practice. METHODS: All patients diagnosed with FIGO I and IIa EOC (2006-2010) in the south of the Netherlands were analyzed. The perc

  16. Identification of six new susceptibility loci for invasive epithelial ovarian cancer

    DEFF Research Database (Denmark)

    Kuchenbaecker, Karoline B; Ramus, Susan J; Tyrer, Jonathan

    2015-01-01

    Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed ass...

  17. Exome genotyping arrays to identify rare and low frequency variants associated with epithelial ovarian cancer risk

    DEFF Research Database (Denmark)

    Permuth, Jennifer B; Pirie, Ailith; Ann Chen, Y

    2016-01-01

    Rare and low frequency variants are not well covered in most germline genotyping arrays and are understudied in relation to epithelial ovarian cancer (EOC) risk. To address this gap, we used genotyping arrays targeting rarer protein-coding variation in 8,165 EOC cases and 11,619 controls from the...

  18. Improved Classification of Epithelial Ovarian Cancer: Results of 3 Danish Cohorts

    DEFF Research Database (Denmark)

    Steffensen, Karina Dahl; Waldstrom, Marianne; Grove, Anni

    2011-01-01

    An increasing body of evidence has suggested that epithelial ovarian cancer (EOC) patients can broadly be divided into 2 groups on the basis of histopathologic parameters and molecular profiles. Type 1 tumors are slow-growing tumors with inherent mutations such as KRAS or BRAF mutations, whereas...

  19. Variation in NF-κB Signaling Pathways and Survival in Invasive Epithelial Ovarian Cancer

    DEFF Research Database (Denmark)

    Block, Matthew S; Charbonneau, Bridget; Vierkant, Robert A

    2014-01-01

    Survival in epithelial ovarian cancer (EOC) is influenced by the host immune response, yet the key genetic determinants of inflammation and immunity that affect prognosis are not known. The nuclear factor-κB (NF-κB) transcription factor family plays an important role in many immune and inflammato...

  20. Identification of six new susceptibility loci for invasive epithelial ovarian cancer

    NARCIS (Netherlands)

    Kuchenbaecker, Karoline B.; Ramus, Susan J.; Tyrer, Jonathan; Lee, Andrew; Shen, Howard C.; Beesley, Jonathan; Lawrenson, Kate; McGuffog, Lesley; Healey, Sue; Lee, Janet M.; Spindler, Tassja J.; Lin, Yvonne G.; Pejovic, Tanja; Bean, Yukie; Li, Qiyuan; Coetzee, Simon; Hazelett, Dennis; Miron, Alexander; Southey, Melissa; Terry, Mary Beth; Goldgar, David E.; Buys, Saundra S.; Janavicius, Ramunas; Dorfling, Cecilia M.; van Rensburg, Elizabeth J.; Neuhausen, Susan L.; Ding, Yuan Chun; Hansen, Thomas V. O.; Jonson, Lars; Gerdes, Anne-Marie; Ejlertsen, Bent; Barrowdale, Daniel; Dennis, Joe; Benitez, Javier; Osorio, Ana; Garcia, Maria Jose; Komenaka, Ian; Weitzel, Jeffrey N.; Ganschow, Pamela; Peterlongo, Paolo; Bernard, Loris; Viel, Alessandra; Bonanni, Bernardo; Peissel, Bernard; Manoukian, Siranoush; Radice, Paolo; Papi, Laura; Ottini, Laura; Fostira, Florentia; Konstantopoulou, Irene; Garber, Judy; Frost, Debra; Perkins, Jo; Platte, Radka; Ellis, Steve; Godwin, Andrew K.; Schmutzler, Rita Katharina; Meindl, Alfons; Engel, Christoph; Sutter, Christian; Sinilnikova, Olga M.; Damiola, Francesca; Mazoyer, Sylvie; Stoppa-Lyonnet, Dominique; Claes, Kathleen; De Leeneer, Kim; Kirk, Judy; Rodriguez, Gustavo C.; Piedmonte, Marion; O'Malley, David M.; de la Hoya, Miguel; Caldes, Trinidad; Aittomaeki, Kristiina; Nevanlinna, Heli; Collee, J. Margriet; Rookus, Matti A.; Oosterwijk, Jan C.; Tihomirova, Laima; Tung, Nadine; Hamann, Ute; Isaccs, Claudine; Tischkowitz, Marc; Imyanitov, Evgeny N.; Caligo, Maria A.; Campbell, Ian G.; Hogervorst, Frans B. L.; Olah, Edith; Diez, Orland; Blanco, Ignacio; Brunet, Joan; Lazaroso, Conxi; Angel Pujana, Miguel; Jakubowska, Anna; Gronwald, Jacek; Lubinski, Jan; Sukiennicki, Grzegorz; Barkardottir, Rosa B.; Plante, Marie; Simard, Jacques; Soucy, Penny; Montagna, Marco; Tognazzo, Silvia; Teixeira, Manuel R.; Pankratz, Vernon S.; Wang, Xianshu; Lindor, Noralane; Szabo, Csilla I.; Kauff, Noah; Vijai, Joseph; Aghajanian, Carol A.; Pfeiler, Georg; Berger, Andreas; Singer, Christian F.; Tea, Muy-Kheng; Phelan, Catherine M.; Greene, Mark H.; Mai, Phuong L.; Rennert, Gad; Mulligan, Anna Marie; Tchatchou, Sandrine; Andrulis, Irene L.; Glendon, Gord; Toland, Amanda Ewart; Jensen, Uffe Birk; Kruse, Torben A.; Thomassen, Mads; Bojesen, Anders; Zidan, Jamal; Friedman, Eitan; Laitman, Yael; Soller, Maria; Liljegren, Annelie; Arver, Brita; Einbeigi, Zakaria; Stenmark-Askmalm, Marie; Olopade, Olufunmilayo I.; Nussbaum, Robert L.; Rebbeck, Timothy R.; Nathanson, Katherine L.; Domchek, Susan M.; Lu, Karen H.; Karlan, Beth Y.; Walsh, Christine; Lester, Jenny; Hein, Alexander; Ekici, Arif B.; Beckmann, Matthias W.; Fasching, Peter A.; Lambrechts, Diether; Van Nieuwenhuysen, Els; Vergote, Ignace; Lambrechts, Sandrina; Dicks, Ed; Doherty, Jennifer A.; Wicklund, Kristine G.; Rossing, Mary Anne; Rudolph, Anja; Chang-Claude, Jenny; Wang-Gohrke, Shan; Eilber, Ursula; Moysich, Kirsten B.; Odunsi, Kunle; Sucheston, Lara; Lele, Shashi; Wilkens, Lynne R.; Goodman, Marc T.; Thompson, Pamela J.; Shvetsov, Yurii B.; Runnebaum, Ingo B.; Duerst, Matthias; Hillemanns, Peter; Doerk, Thilo; Antonenkova, Natalia; Bogdanova, Natalia; Leminen, Arto; Pelttari, Liisa M.; Butzow, Ralf; Modugno, Francesmary; Kelley, Joseph L.; Edwards, Robert P.; Ness, Roberta B.; du Bois, Andreas; Heitz, Florian; Schwaab, Ira; Harter, Philipp; Matsuo, Keitaro; Hosono, Satoyo; Orsulic, Sandra; Jensen, Allan; Kjaer, Susanne Kruger; Hogdall, Estrid; Hasmad, Hanis Nazihah; Azmi, Mat Adenan Noor; Teo, Soo-Hwang; Woo, Yin-Ling; Fridley, Brooke L.; Goode, Ellen L.; Cunningham, Julie M.; Vierkant, Robert A.; Bruinsma, Fiona; Giles, Graham G.; Liang, Dong; Hildebrandt, Michelle A. T.; Wu, Xifeng; Levine, Douglas A.; Bisogna, Maria; Berchuck, Andrew; Iversen, Edwin S.; Schildkraut, Joellen M.; Concannon, Patrick; Weber, Rachel Palmieri; Cramer, Daniel W.; Terry, Kathryn L.; Poole, Elizabeth M.; Tworoger, Shelley S.; Bandera, Elisa V.; Orlow, Irene; Olson, Sara H.; Krakstad, Camilla; Salvesen, Helga B.; Tangen, Ingvild L.; Bjorge, Line; van Altena, Anne M.; Aben, Katja K. H.; Kiemeney, Lambertus A.; Massuger, Leon F. A. G.; Kellar, Melissa; Brooks-Wilson, Angela; Kelemen, Linda E.; Cook, Linda S.; Le, Nhu D.; Cybulski, Cezary; Yang, Hannah; Lissowska, Jolanta; Brinton, Louise A.; Wentzensen, Nicolas; Hogdall, Claus; Lundvall, Lene; Nedergaard, Lotte; Baker, Helen; Song, Honglin; Eccles, Diana; McNeish, Ian; Paul, James; Carty, Karen; Siddiqui, Nadeem; Glasspool, Rosalind; Whittemore, Alice S.; Rothstein, Joseph H.; McGuire, Valerie; Sieh, Weiva; Ji, Bu-Tian; Zheng, Wei; Shu, Xiao-Ou; Gao, Yu-Tang; Rosen, Barry; Risch, Harvey A.; McLaughlin, John R.; Narod, Steven A.; Monteiro, Alvaro N.; Chen, Ann; Lin, Hui-Yi; Permuth-Wey, Jenny; Sellers, Thomas A.; Tsai, Ya-Yu; Chen, Zhihua; Ziogas, Argyrios; Anton-Culver, Hoda; Gentry-Maharaj, Aleksandra; Menon, Usha; Harrington, Patricia; Lee, Alice W.; Wu, Anna H.; Pearce, Celeste L.; Coetzee, Gerry; Pike, Malcolm C.; Dansonka-Mieszkowska, Agnieszka; Timorek, Agnieszka; Rzepecka, Iwona K.; Kupryjanczyk, Jolanta; Freedman, Matt; Noushmehr, Houtan; Easton, Douglas F.; Offit, Kenneth; Couch, Fergus J.; Gayther, Simon; Pharoah, Paul P.; Antoniou, Antonis C.; Chenevix-Trench, Georgia

    2015-01-01

    Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed associ

  1. Common variants at the CHEK2 gene locus and risk of epithelial ovarian cancer

    NARCIS (Netherlands)

    Lawrenson, K.; Iversen, E.S.; Tyrer, J.; Weber, R.P.; Concannon, P.; Hazelett, D.J.; Li, Q.; Marks, J.R.; Berchuck, A.; Lee, J.M.; Aben, K.K.H.; Anton-Culver, H.; Antonenkova, N.; Bandera, E.V.; Bean, Y.; Beckmann, M.W.; Bisogna, M.; Bjorge, L.; Bogdanova, N.; Brinton, L.A.; Brooks-Wilson, A.; Bruinsma, F.; Butzow, R.; Campbell, I.G.; Carty, K.; Chang-Claude, J.; Chenevix-Trench, G.; Chen, A; Chen, Z.; Cook, L.S.; Cramer, D.W; Cunningham, J.M.; Cybulski, C.; Plisiecka-Halasa, J.; Dennis, J.; Dicks, E.; Doherty, J.A.; Dork, T.; Bois, A. du; Eccles, D.; Easton, D.T.; Edwards, R.P.; Eilber, U.; Ekici, A.B.; Fasching, P.A.; Fridley, B.L.; Gao, Y.T.; Gentry-Maharaj, A.; Giles, G.G.; Glasspool, R.; Goode, E.L.; Goodman, M.T.; Gronwald, J.; Harter, P.; Hasmad, H.N.; Hein, A.; Heitz, F.; Hildebrandt, M.A.T.; Hillemanns, P.; Hogdall, E.; Hogdall, C.; Hosono, S.; Jakubowska, A.; Paul, J.; Jensen, A.; Karlan, B.Y.; Kjaer, S.K.; Kelemen, L.E.; Kellar, M.; Kelley, J.L.; Kiemeney, L.A.; Krakstad, C.; Lambrechts, D.; Lambrechts, S.; Le, N.D.; Lee, A.W.; Cannioto, R.; Leminen, A.; Lester, J.; Levine, D.A.; Liang, D.; Lissowska, J.; Lu, K.; Lubinski, J.; Lundvall, L.; Massuger, L.F.; Matsuo, K.; McGuire, V.; McLaughlin, J.R.; Nevanlinna, H.; McNeish, I.; Menon, U.; Modugno, F.; Moysich, K.B.; Narod, S.A.; Nedergaard, L.; Ness, R.B.; Azmi, M.A. Noor; Odunsi, K.; Olson, S.H.

    2015-01-01

    Genome-wide association studies have identified 20 genomic regions associated with risk of epithelial ovarian cancer (EOC), but many additional risk variants may exist. Here, we evaluated associations between common genetic variants [single nucleotide polymorphisms (SNPs) and indels] in DNA repair g

  2. Identification of six new susceptibility loci for invasive epithelial ovarian cancer

    NARCIS (Netherlands)

    K.B. Kuchenbaecker (Karoline); S.J. Ramus (Susan); J.P. Tyrer (Jonathan); A. Lee (Andrew); H.C. Shen (Howard C.); J. Beesley (Jonathan); K. Lawrenson (Kate); L. McGuffog (Lesley); S. Healey (Sue); J.M. Lee (Janet M.); T.J. Spindler (Tassja J.); Y.G. Lin (Yvonne G.); T. Pejovic (Tanja); Y. Bean (Yukie); Q. Li (Qiyuan); S. Coetzee (Simon); D. Hazelett (Dennis); A. Miron (Alexander); M.C. Southey (Melissa); M.B. Terry (Mary Beth); D. Goldgar (David); S.S. Buys (Saundra); R. Janavicius (Ramunas); C.M. Dorfling (Cecilia); E.J. van Rensburg (Elizabeth); S.L. Neuhausen (Susan); Y.C. Ding (Yuan); T.V.O. Hansen (Thomas); L. Jønson (Lars); A.-M. Gerdes (Anne-Marie); B. Ejlertsen (Bent); D. Barrowdale (Daniel); J. Dennis (Joe); J. Benítez (Javier); A. Osorio (Ana); M.J. Garcia (Maria Jose); I. Komenaka (Ian); J.N. Weitzel (Jeffrey); P. Ganschow (Pamela); P. Peterlongo (Paolo); L. Bernard (Loris); A. Viel (Alessandra); B. Bonnani (Bernardo); B. Peissel (Bernard); S. Manoukian (Siranoush); P. Radice (Paolo); L. Papi (Laura); L. Ottini (Laura); F. Fostira (Florentia); I. Konstantopoulou (I.); J. Garber (Judy); D. Frost (Debra); J. Perkins (Jo); R. Platte (Radka); S.D. Ellis (Steve); A.K. Godwin (Andrew K.); R.K. Schmutzler (Rita); A. Meindl (Alfons); C. Engel (Christoph); C. Sutter (Christian); O. Sinilnikova (Olga); F. Damiola (Francesca); S. Mazoyer (Sylvie); D. Stoppa-Lyonnet (Dominique); K.B.M. Claes (Kathleen B.M.); K. De Leeneer (Kim); J. Kirk (Judy); G. Rodriguez (Gustavo); M. Piedmonte (Marion); D.M. O'Malley (David M.); M. de La Hoya (Miguel); T. Caldes (Trinidad); K. Aittomäki (Kristiina); H. Nevanlinna (Heli); J.C. Margriet (J. Collée); M.A. Rookus (Matti); J.C. Oosterwijk (Jan); L. Tihomirova (Laima); N. Tung (Nadine); U. Hamann (Ute); C. Isaccs (Claudine); M. Tischkowitz (Marc); E.N. Imyanitov (Evgeny); M.A. Caligo (Maria); I. Campbell (Ian); F.B.L. Hogervorst (Frans); E. Olah; O. Díez (Orland); I. Blanco (Ignacio); J. Brunet (Joan); C. Lazaro (Conxi); M.A. Pujana (Miguel); A. Jakubowska (Anna); J. Gronwald (Jacek); J. Lubinski (Jan); G. Sukiennicki (Grzegorz); R.B. Barkardottir (Rosa); M. Plante (Marie); J. Simard (Jacques); P. Soucy (Penny); M. Montagna (Marco); S. Tognazzo (Silvia); P.J. Teixeira; V.S. Pankratz (Shane); X. Wang (Xianshu); N.M. Lindor (Noralane); C. Szabo (Csilla); N. Kauff (Noah); J. Vijai (Joseph); C.A. Aghajanian (Carol A.); G. Pfeiler (Georg); A. Berger (Andreas); C.F. Singer (Christian); M.-K. Tea; C. Phelan (Catherine); M.H. Greene (Mark H.); P.L. Mai (Phuong); G. Rennert (Gad); A.-M. Mulligan (Anna-Marie); S. Tchatchou (Sandrine); I.L. Andrulis (Irene); G. Glendon (Gord); A.E. Toland (Amanda); U.B. Jensen (Uffe Birk); T.A. Kruse (Torben); M. Thomassen (Mads); A. Bojesen (Anders); J. Zidan (Jamal); E. Friedman (Eitan); Y. Laitman (Yael); M. Soller (Maria); A. Liljegren (Annelie); B. Arver (Brita Wasteson); Z. Einbeigi (Zakaria); M. Stenmark-Askmalm (Marie); O.I. Olopade (Olufunmilayo I.); R.L. Nussbaum (Robert L.); T.R. Rebbeck (Timothy R.); K.L. Nathanson (Katherine); S.M. Domchek (Susan); K.H. Lu (Karen); B.Y. Karlan (Beth Y.); C. Walsh (Christine); K.J. Lester (Kathryn); R. Hein (Rebecca); A.B. Ekici (Arif); M.W. Beckmann (Matthias W.); P.A. Fasching (Peter); D. Lambrechts (Diether); E. Van Nieuwenhuysen (Els); I. Vergote (Ignace); S. Lambrechts (Sandrina); E. Dicks (Ed); J.A. Doherty (Jennifer A.); K.G. Wicklund (Kristine G.); M.A. Rossing (Mary Anne); A. Rudolph (Anja); J. Chang-Claude (Jenny); S. Wang-Gohrke (Shan); U. Eilber (Ursula); K.B. Moysich (Kirsten B.); K. Odunsi (Kunle); L. Sucheston (Lara); S. Lele (Shashi); L. Wilkens (Lynne); M.T. Goodman (Marc); P.J. Thompson (Pamela J.); Y.B. Shvetsov (Yurii B.); I.B. Runnebaum (Ingo); M. Dürst (Matthias); P. Hillemanns (Peter); T. Dörk (Thilo); N.N. Antonenkova (Natalia); N.V. Bogdanova (Natalia); A. Leminen (Arto); L.M. Pelttari (Liisa); R. Butzow (Ralf); F. Modugno (Francesmary); J.L. Kelley (Joseph L.); R. Edwards (Robert); R.B. Ness (Roberta); A. Du Bois (Andreas); P.U. Heitz; I. Schwaab (Ira); P. Harter (Philipp); K. Matsuo (Keitaro); N. Hosono (Naoya); S. Orsulic (Sandra); A. Jensen (Allan); M. Kjaer (Michael); E. Høgdall (Estrid); H.N. Hasmad (Hanis Nazihah); M.A. Noor Azmi (Mat Adenan); S.-H. Teo; Y.L. Woo (Yin Ling); B.L. Fridley (Brooke); E.L. Goode (Ellen); J.M. Cunningham (Julie); R.A. Vierkant (Robert); F. Bruinsma (Fiona); G.G. Giles (Graham G.); D. Liang (Dong); M.A.T. Hildebrandt (Michelle A.T.); X. Wu (Xifeng); D.A. Levine (Douglas); M. Bisogna (Maria); A. Berchuck (Andrew); E. Iversen (Erik); J.M. Schildkraut (Joellen); P. Concannon (Patrick); R.P. Weber (Rachel Palmieri); D.W. Cramer (Daniel); K.L. Terry (Kathryn); E.M. Poole (Elizabeth); S. Tworoger (Shelley); E.V. Bandera (Elisa); I. Orlow (Irene); S.H. Olson (Sara); C. Krakstad (Camilla); H.B. Salvesen (Helga); I.L. Tangen (Ingvild L.); L. Bjorge (Line); A.M. van Altena (Anne); K.K.H. Aben (Katja); L.A.L.M. Kiemeney (Bart); L.F. Massuger (Leon); M. Kellar (Melissa); A. Brooks-Wilson (Angela); L.E. Kelemen (Linda); L.S. Cook (Linda S.); N.D. Le (Nhu D.); C. Cybulski (Cezary); H. Yang (Hannah); J. Lissowska (Jolanta); L.A. Brinton (Louise); N. Wentzensen (N.); C.K. Høgdall (Claus); L. Lundvall (Lene); L. Nedergaard (Lotte); H. Baker (Helen); H. Song (Honglin); D. Eccles (Diana); I. McNeish (Ian); J. Paul (James); K. Carty (Karen); N. Siddiqui (Nadeem); R. Glasspool (Rosalind); A.S. Whittemore (Alice S.); J.H. Rothstein (Joseph H.); W.P. McGuire; W. Sieh (Weiva); B.-T. Ji (Bu-Tian); W. Zheng (Wei); X.-O. Shu (Xiao-Ou); Y. Gao; B. Rosen (Barry); H. Risch (Harvey); J. McLaughlin (John); S.A. Narod (Steven A.); A.N.A. Monteiro (Alvaro N.); A. Chen (Ann); H.-Y. Lin (Hui-Yi); J. Permuth-Wey (Jenny); T.F. Sellers; Y.-Y. Tsai (Ya-Yu); Z. Chen (Zhihua); A. Ziogas (Argyrios); H. Anton-Culver (Hoda); A. Gentry-Maharaj (Aleksandra); U. Menon (Usha); P. harrington (Patricia); A.W. Lee (Alice W.); A.H. Wu (Anna H.); C.L. Pearce (Celeste); G. Coetzee (Gerry); M.C. Pike (Malcolm C.); A. Dansonka-Mieszkowska (Agnieszka); A. Timorek (Agnieszka); I.K. Rzepecka (Iwona); J. Kupryjanczyk (Jolanta); M. Freedman (Matthew); H. Noushmehr (Houtan); D.F. Easton (Douglas F.); K. Offit (Kenneth); F.J. Couch (Fergus); S.A. Gayther (Simon); P.P.D.P. Pharoah (Paul P.D.P.); A.C. Antoniou (Antonis C.); G. Chenevix-Trench (Georgia)

    2015-01-01

    textabstractGenome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we ass

  3. Resistance to first line platinum paclitaxel chemotherapy in serous epithelial ovarian cancer

    DEFF Research Database (Denmark)

    Steffensen, Karina Dahl; Smoter, Marta; Waldstrøm, Marianne

    2014-01-01

    of sensitivity to platinum/paclitaxel treatment. The primary aim of the study was to investigate whether ERCC1 and Tau protein expression correlates with patient outcome in newly diagnosed epithelial ovarian cancer (EOC) patients. Formalin-fixed, paraffin-embedded tissue sections from 227 newly diagnosed EOC...

  4. Recent technological advances in using mouse models to study ovarian cancer.

    Science.gov (United States)

    House, Carrie Danielle; Hernandez, Lidia; Annunziata, Christina Messineo

    2014-01-01

    Serous epithelial ovarian cancer (SEOC) is the most lethal gynecological cancer in the United States with disease recurrence being the major cause of morbidity and mortality. Despite recent advances in our understanding of the molecular mechanisms responsible for the development of SEOC, the survival rate for women with this disease has remained relatively unchanged in the last two decades. Preclinical mouse models of ovarian cancer, including xenograft, syngeneic, and genetically engineered mice, have been developed to provide a mechanism for studying the development and progression of SEOC. Such models strive to increase our understanding of the etiology and dissemination of ovarian cancer in order to overcome barriers to early detection and resistance to standard chemotherapy. Although there is not a single model that is most suitable for studying ovarian cancer, improvements have led to current models that more closely mimic human disease in their genotype and phenotype. Other advances in the field, such as live animal imaging techniques, allow effective monitoring of the microenvironment and therapeutic efficacy. New and improved preclinical mouse models, combined with technological advances to study such models, will undoubtedly render success of future human clinical trials for patients with SEOC.

  5. Expression of Wnt-1,beta-catenin and c-myc in Ovarian Epithelial Tumor and Its Implication

    Institute of Scientific and Technical Information of China (English)

    LIN Xiao; HU Zhuo-ying

    2008-01-01

    Objective:To investigate the expression of Wnt-1, beta-catenin and c-myc in normal ovarian epithelial cell and malignant ovarian epithelial tumor. Methods:Immunohistochemical staining with SP method was conducted to identify the expression of Wnt-1,beta-catenin and c-myc in 18 samples of normal epithelial tissue and 34 cases of malignant epithelial tumor of ovary. Results:The expression rate of Wnt-1 and c-myc in malignant epithelial tumors was higher than those in normal epithelial cell(P<0.05).The abnormal expression rate of beta-catenin in malignant ovarian epithelial tumors was higher than that in normal epithelial cell(P<0.05).A significant positive correlation was found between Wnt-1, beta-catenin and c-myc in malignant ovarian epithelial tumor(P<0.05).A significant difierence of expressions of Beta-catenin and C-myc was found between serous and mutinous tumors (P<0.05). Conclusion:The abnormal expression of Wnt-1,beta-catenin and c-myc might indicate the malignant transformation in ovarian epithelial tumors.

  6. Response to microtubule-interacting agents in primary epithelial ovarian cancer cells

    Science.gov (United States)

    2013-01-01

    Background Ovarian cancer constitutes nearly 4% of all cancers among women and is the leading cause of death from gynecologic malignancies in the Western world. Standard first line adjuvant chemotherapy treatments include Paclitaxel (Taxol) and platinum-based agents. Taxol, epothilone B (EpoB) and discodermolide belong to a family of anti-neoplastic agents that specifically interferes with microtubules and arrests cells in the G2/M phase of the cell cycle. Despite initial success with chemotherapy treatment, many patients relapse due to chemotherapy resistance. In vitro establishment of primary ovarian cancer cells provides a powerful tool for better understanding the mechanisms of ovarian cancer resistance. We describe the generation and characterization of primary ovarian cancer cells derived from ascites fluids of patients with epithelial ovarian cancer. Methods Chemosensitivity of these cell lines to Taxol, EpoB and discodermolide was tested, and cell cycle analysis was compared to that of immortalized ovarian cancer cell lines SKOV3 and Hey. The relationship between drug resistance and αβ-tubulin and p53 status was also investigated. Results All newly generated primary cancer cells were highly sensitive to the drugs. αβ-tubulin mutation was not found in any primary cell lines tested. However, one cell line that harbors p53 mutation at residue 72 (Arg to Pro) exhibits altered cell cycle profile in response to all drug treatments. Immortalized ovarian cancer cells respond differently to EpoB treatment when compared to primary ovarian cancer cells, and p53 polymorphism suggests clinical significance in the anti-tumor response in patients. Conclusions The isolation and characterization of primary ovarian cancer cells from ovarian cancer patients’ specimens contribute to further understanding the nature of drug resistance to microtubule interacting agents (MIAs) currently used in clinical settings. PMID:23574945

  7. Tetraploid cells from cytokinesis failure induce aneuploidy and spontaneous transformation of mouse ovarian surface epithelial cells.

    Science.gov (United States)

    Lv, Lei; Zhang, Tianwei; Yi, Qiyi; Huang, Yun; Wang, Zheng; Hou, Heli; Zhang, Huan; Zheng, Wei; Hao, Qiaomei; Guo, Zongyou; Cooke, Howard J; Shi, Qinghua

    2012-08-01

    Most ovarian cancers originate from the ovarian surface epithelium and are characterized by aneuploid karyotypes. Aneuploidy, a consequence of chromosome instability, is an early event during the development of ovarian cancers. However, how aneuploid cells are evolved from normal diploid cells in ovarian cancers remains unknown. In the present study, cytogenetic analyses of a mouse syngeneic ovarian cancer model revealed that diploid mouse ovarian surface epithelial cells (MOSECs) experienced an intermediate tetraploid cell stage, before evolving to aneuploid (mainly near-tetraploid) cells. Using long-term live-cell imaging followed by fluorescence in situ hybridization (FISH), we demonstrated that tetraploid cells originally arose from cytokinesis failure of bipolar mitosis in diploid cells, and gave rise to aneuploid cells through chromosome mis-segregation during both bipolar and multipolar mitoses. Injection of the late passage aneuploid MOSECs resulted in tumor formation in C57BL/6 mice. Therefore, we reveal a pathway for the evolution of diploid to aneuploid MOSECs and elucidate a mechanism for the development of near-tetraploid ovarian cancer cells.

  8. EFFECTS OF MUTATION AND EXPRESSION OF PTEN GENE mRNA ON TUMORIGENESIS AND PROGRESSION OF EPITHELIAL OVARIAN CANCER

    Institute of Scientific and Technical Information of China (English)

    陈颖; 郑华川; 杨雪飞; 孙丽梅; 辛彦

    2004-01-01

    Objective To investigate the mutation and expression of tumor suppressor gene-PTEN mRNA and explore their roles in tumorigenesis and progression of ovarian cancer. Methods Mutated exon 5 of PTEN gene was examined in normal ovary (n = 5), ovarian cyst (n =5), ovarian borderline tumor (n=9), epithelial ovarian cancer (n=60), and ovarian cancer cell line (n= 1)by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). mRNA expression of PTEN gene was evaluated in corresponding tissues and cell line by reverse transcription polymerase chain reaction(RT-PCR). The mutation and mRNA expression of PTEN gene were compared with clinicopathological features of ovarian cancer. Results Mutated exon 5 of PTEN gene was detected only in 5 (7.1%) cases of epithelial ovarian cancer. mRNA expression level of PTEN gene in ovarian borderline tumor or ovarian cancer was lower than that in normal ovary or ovarian cyst (P < 0.05). The level of PTEN gene mRNA expression was negatively correlated with clinicopathological staging of ovarian cancer, whereas positively correlated with histological differentiation (P < 0.05). mRNA expression level of PTEN gene in ovarian endometrioid cancer was significantly lower than that in ovarian serous or mucinous cancer (P < 0.05). Conclusions Mutation of PTEN gene occurs in ovarian cancer. Down-regulated expression of PTEN is probably an important molecular event in tumorigenesis of ovarian cancer. Abnormal expression of PTEN gene is involved in progression of ovarian cancer. Reduced expression of PTEN gene is closely associated with tumorigenesis and pathobiological behaviors of ovarian endometrioid cancer.

  9. EXPRESSION AND SIGNIFICANCE OF BASIC FIBROBLAST GWOWTH FACTOR AND FIBROBLAST GROWTH FACTOR RECEPTOR-1 IN OVARIAN EPITHELIAL NEOPLASM

    Institute of Scientific and Technical Information of China (English)

    高尚风; 杨蓉; 高博; 刘惠喜

    2003-01-01

    fibroblast growth factor (bFGF), fibroblast growth factor receptor-1 (FGFR-1) and carcinogenesis and progression of ovarian epithelial neoplasm. Methods Ten cases of normal ovarian tissues and 75 cases of ovarian epithelial neoplasm tissues were detected by immunohistochemical methods: S-P for bFGF, FGFR-1,double immunohistochemistry Lab-SA for Ki-67 antigen and bFGF. Results The expression level of bFGF, FGFR-1in ovarian epithelium and ovarian epithelial neoplasm showed a step-wise increase in the following order:normal〈benign〈borderline〈malignant; The expression level and intensity of bFGF and FGFR-1 were increased with the decrease of differentiation degree and increase of clinical stage in ovarian carcinoma; There was no statistical difference between the expression of bFGF, FGFR-1 in serous cystadenocarcinoma and that of mucinous cystadenocarcinoma; The expression of bFGF was correlated with that of FGFR-1 in neoplastic tissues; There were positive expression rates of bFGF and Ki-67 antigen in ovarian epithelial neoplasm. Conclusion As an important proliferative factor, bFGF plays an important role in carcinogenisis and progression of ovarian epithelial neoplasm.

  10. Tumour suppressor genes in sporadic epithelial ovarian cancer

    DEFF Research Database (Denmark)

    Liu, Ying; Ganesan, Trivadi S

    2002-01-01

    of the evolution of tumour progression. A major focus of research has been to identify tumour suppressor genes implicated in sporadic ovarian cancer over the past decade. Several tumour suppressor genes have been identified by strategies such as positional cloning and differential expression display. Further...

  11. Coffee, tea, and caffeine consumption and risk of epithelial ovarian cancer and borderline ovarian tumors

    DEFF Research Database (Denmark)

    Gosvig, Camilla F; Kjaer, Susanne K; Blaakær, Jan

    2015-01-01

    tumors. By use of data from a large Danish population-based case-control study, we examined the risk of ovarian tumors associated with coffee, tea, and caffeine consumption with a particular focus on characterizing risks by tumor behavior and histology. MATERIAL AND METHODS: From 1995 through 1999, we...... included 267 women with ovarian cancer, 115 women with borderline ovarian tumors and 911 randomly selected control women. All women completed a beverage frequency questionnaire with detailed information on coffee and tea consumption. Analyses were performed using multiple logistic regression models...

  12. A THREE YEAR RETROSPECTIVE STUDY OF OVARIAN NEOPLASMS WITH SPECIAL EMPHASIS ON SURFACE EPITHELIAL TUMOURS

    Directory of Open Access Journals (Sweden)

    Krishna Bharathi Yarlagadda

    2016-07-01

    Full Text Available BACKGROUND Ovarian tumours being second most common gynaecological cancer in India account for 30% of all cancers of female genital tract. Study conducted to determine relative frequencies of various histological types based on WHO classification and their age distribution with particular emphasis on surface epithelial tumours. This study is undertaken to find out the frequency of incidence of different histopathological subtypes with particular emphasis on surface epithelial tumours and age distribution of ovarian tumours in our institute located in coastal Andhra Pradesh. METHODS This is a retrospective study of 100 cases of ovarian neoplasms collected during a period of 3 years from June 2013 to May 2016 from the Department of Pathology, Katuri Medical College and Hospital, Chinakondrupadu, Guntur, A. P, India. The patients attending our hospital are mostly from rural areas around. Paraffin blocks of all 100 ovarian neoplasms retrieved. Complete clinical and radiological findings analysed from our records. RESULTS The tumours are grouped according to the nature of tumour whether benign or borderline or malignant according to cell of origin, histological subtyping, and age group. Surface epithelial tumours are the most common. Benign tumours outnumber the malignant tumours. Benign ovarian tumours showed a peak in 21-40 Yrs. age group and malignant in the age group of 41- 60 Yrs. Results of our study compared with other studies. CONCLUSION Because of the geographic location, poverty, and illiteracy, patients seek medical advice late. So, awareness among public by health education, passive surveillance, and community screening facility will be helpful in early detection of ovarian neoplasms.

  13. Genetic and epigenetic heterogeneity of epithelial ovarian cancer and the clinical implications for molecular targeted therapy.

    Science.gov (United States)

    Bai, Huimin; Cao, Dongyan; Yang, Jiaxin; Li, Menghui; Zhang, Zhenyu; Shen, Keng

    2016-04-01

    Epithelial ovarian cancer (EOC) is the most lethal gynaecological malignancy, and tumoural heterogeneity (TH) has been blamed for treatment failure. The genomic and epigenomic atlas of EOC varies significantly with tumour histotype, grade, stage, sensitivity to chemotherapy and prognosis. Rapidly accumulating knowledge about the genetic and epigenetic events that control TH in EOC has facilitated the development of molecular-targeted therapy. Poly (ADP-ribose) polymerase (PARP) inhibitors, designed to target homologous recombination, are poised to change how breast cancer susceptibility gene (BRCA)-related ovarian cancer is treated. Epigenetic treatment regimens being tested in clinical or preclinical studies could provide promising novel treatment approaches and hope for improving patient survival.

  14. microRNA-181a has a critical role in ovarian cancer progression through the regulation of the epithelial-mesenchymal transition

    Science.gov (United States)

    Parikh, Aditya; Lee, Christine; Joseph, Peronne; Marchini, Sergio; Baccarini, Alessia; Kolev, Valentin; Romualdi, Chiara; Fruscio, Robert; Shah, Hardik; Wang, Feng; Mullokandov, Gavriel; Fishman, David; D'Incalci, Maurizio; Rahaman, Jamal; Kalir, Tamara; Redline, Raymond W.; Brown, Brian D.; Narla, Goutham; Difeo, Analisa

    2014-01-01

    Ovarian cancer is a leading cause of cancer deaths among women. Effective targets to treat advanced epithelial ovarian cancer (EOC) and biomarkers to predict treatment response are still lacking because of the complexity of pathways involved in ovarian cancer progression. Here we show that miR-181a promotes TGF-β-mediated epithelial-to-mesenchymal transition via repression of its functional target, Smad7. miR-181a and phosphorylated Smad2 are enriched in recurrent compared with matched-primary ovarian tumours and their expression is associated with shorter time to recurrence and poor outcome in patients with EOC. Furthermore, ectopic expression of miR-181a results in increased cellular survival, migration, invasion, drug resistance and in vivo tumour burden and dissemination. In contrast, miR-181a inhibition via decoy vector suppression and Smad7 re-expression results in significant reversion of these phenotypes. Combined, our findings highlight an unappreciated role for miR-181a, Smad7, and the TGF-β signalling pathway in high-grade serous ovarian cancer.

  15. Immunoexpression of matrix metalloproteinase-2 (MMP-2) in epithelial ovarian cancers (EOCs)

    Institute of Scientific and Technical Information of China (English)

    Ibrahim A Abdelazim; Mohannad Lutfi Abu faza; Mohammed Al-Kadi

    2013-01-01

    Objective: To evaluate the relation between matrix metalloproteinase-2 (MMP-2) expression and the clinical and/or pathological parameters of the epithelial ovarian cancers (EOCs). Methods: Forty-two (42) patients with EOCs diagnosed after histopathological examination of the specimens were included in this study. The pathological specimens were additionally stained by immunoperoxidase technique for MMP-2 using a monoclonal antibody against activated MMP 2. The staining intensity of MMP-2 was correlated with the clinical and pathological parameters of the studied cases, including patient's age, surgical stage, histological grade, omental, and lymph node metastasis. Results: The studied cases of EOCs were classified according to the intensity or the degree of MMP-2 expression, as; seven cases (16.7%) negative, eighteen cases (42.8%) weak, seven cases (16.7%) moderate and ten cases (23.8%) intense for MMP-2 staining. There was a significant positive correlation between MMP-2 expression and the histological grades and the surgical stages of the studied EOC (r <1, P<0.05), while, there was no significant relation between MMP-2 expression and the histopathological types of the studied EOCs. MMP-2 expression was significantly high in EOCs with ascites, omental, distant and uterine metastasis, while, there was no significant relation between MMP-2 expressions and lymph node metastasis or bilaterality of the EOCs. Conclusions: MMP-2 expression was associated with advanced, aggressive EOCs and there was direct relation between expression of MMP-2 and degree of invasiveness and metastasis of EOCs.

  16. Inhibition of RUNX2 transcriptional activity blocks the proliferation, migration and invasion of epithelial ovarian carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Zhi-Qiang Wang

    Full Text Available Previously, we have identified the RUNX2 gene as hypomethylated and overexpressed in post-chemotherapy (CT primary cultures derived from serous epithelial ovarian cancer (EOC patients, when compared to primary cultures derived from matched primary (prior to CT tumors. However, we found no differences in the RUNX2 methylation in primary EOC tumors and EOC omental metastases, suggesting that DNA methylation-based epigenetic mechanisms have no impact on RUNX2 expression in advanced (metastatic stage of the disease. Moreover, RUNX2 displayed significantly higher expression not only in metastatic tissue, but also in high-grade primary tumors and even in low malignant potential tumors. Knockdown of the RUNX2 expression in EOC cells led to a sharp decrease of cell proliferation and significantly inhibited EOC cell migration and invasion. Gene expression profiling and consecutive network and pathway analyses confirmed these findings, as various genes and pathways known previously to be implicated in ovarian tumorigenesis, including EOC tumor invasion and metastasis, were found to be downregulated upon RUNX2 suppression, while a number of pro-apoptotic genes and some EOC tumor suppressor genes were induced. Taken together, our data are indicative for a strong oncogenic potential of the RUNX2 gene in serous EOC progression and suggest that RUNX2 might be a novel EOC therapeutic target. Further studies are needed to more completely elucidate the functional implications of RUNX2 and other members of the RUNX gene family in ovarian tumorigenesis.

  17. Inhibition of RUNX2 transcriptional activity blocks the proliferation, migration and invasion of epithelial ovarian carcinoma cells.

    Science.gov (United States)

    Wang, Zhi-Qiang; Keita, Mamadou; Bachvarova, Magdalena; Gobeil, Stephane; Morin, Chantale; Plante, Marie; Gregoire, Jean; Renaud, Marie-Claude; Sebastianelli, Alexandra; Trinh, Xuan Bich; Bachvarov, Dimcho

    2013-01-01

    Previously, we have identified the RUNX2 gene as hypomethylated and overexpressed in post-chemotherapy (CT) primary cultures derived from serous epithelial ovarian cancer (EOC) patients, when compared to primary cultures derived from matched primary (prior to CT) tumors. However, we found no differences in the RUNX2 methylation in primary EOC tumors and EOC omental metastases, suggesting that DNA methylation-based epigenetic mechanisms have no impact on RUNX2 expression in advanced (metastatic) stage of the disease. Moreover, RUNX2 displayed significantly higher expression not only in metastatic tissue, but also in high-grade primary tumors and even in low malignant potential tumors. Knockdown of the RUNX2 expression in EOC cells led to a sharp decrease of cell proliferation and significantly inhibited EOC cell migration and invasion. Gene expression profiling and consecutive network and pathway analyses confirmed these findings, as various genes and pathways known previously to be implicated in ovarian tumorigenesis, including EOC tumor invasion and metastasis, were found to be downregulated upon RUNX2 suppression, while a number of pro-apoptotic genes and some EOC tumor suppressor genes were induced. Taken together, our data are indicative for a strong oncogenic potential of the RUNX2 gene in serous EOC progression and suggest that RUNX2 might be a novel EOC therapeutic target. Further studies are needed to more completely elucidate the functional implications of RUNX2 and other members of the RUNX gene family in ovarian tumorigenesis.

  18. ESR1/SYNE1 polymorphism and invasive epithelial ovarian cancer risk: an Ovarian Cancer Association Consortium study

    DEFF Research Database (Denmark)

    Doherty, Jennifer A; Rossing, Mary Anne; Cushing-Haugen, Kara L;

    2010-01-01

    We genotyped 13 single nucleotide polymorphisms (SNPs) in the estrogen receptor alpha gene (ESR1) region in three population-based case-control studies of epithelial ovarian cancer conducted in the United States, comprising a total of 1,128 and 1,866 non-Hispanic white invasive cases and controls......, respectively. A SNP 19 kb downstream of ESR1 (rs2295190, G-to-T change) was associated with invasive ovarian cancer risk, with a per-T-allele odds ratio (OR) of 1.24 [95% confidence interval (CI), 1.06-1.44, P = 0.006]. rs2295190 is a nonsynonymous coding SNP in a neighboring gene called spectrin repeat...... containing, nuclear envelope 1 (SYNE1), which is involved in nuclear organization and structural integrity, function of the Golgi apparatus, and cytokinesis. An isoform encoded by SYNE1 has been reported to be downregulated in ovarian and other cancers. rs2295190 was genotyped in an additional 12 studies...

  19. [The expression of MKP-1 and p-ERK(1/2) in primary ovarian epithelial tumor tissues].

    Science.gov (United States)

    Zhou, Jian Wei; Gan, Ning Yue; Zhang, Wei Jiang

    2009-06-01

    To investigate the expression of mitogen activated protein kinase phosphatase-1 (MKP-1) and phosphorylation extracellular signal-regulated kinases (p-ERK(1/2)) in primary ovarian epithelial tumor tissues, and provide experiment's foundation on the new treatment in ovarian cancer. Expression of MKP-1 and p-ERK(1/2) in tissues from 64 patients with primary ovarian epithelial tumor, 35 patients with ovarian epithelial bordline tumor, 32 patients with ovarian epithelial benign tumor and 26 normal ovarian tissues was detected by immunohistochemistry. Western-blot was also used for detecting the expression of MKP-1 and p-ERK(1/2) protein in these tissues. Immunohistochemistry and Western-blot assay showed that the expression of MKP-1 was gradually decreased in normal ovarian tissues, benign tumor, bordline tumor and carcinoma respectively, and there were significant differences among them (P ERK(1/2) was gradually increased in normal ovarian tissues, benign tumor, bordline tumor and carcinoma respectively, and there were also significant differences among them (P ERK(1/2) expression level in the carcinoma tissues of stage III/IV patients was significantly higher than that of stage I/II patients. Expression of MKP-1 and p-ERK(1/2) in same ovarian carcinoma tissues detected by immunohistochemistry and Western-blot assay showed significant negative correlation (r = -0.90, P ERKs may play a role in the development of ovarian carcinoma. The abnormal expression of MKP-1 and p-ERK(1/2) probably assists in promoting the development and progression of ovarian carcinoma.

  20. Prolactin receptor-mediated internalization of imaging agents detects epithelial ovarian cancer

    Science.gov (United States)

    Sundaram, Karthik M.

    Epithelial ovarian cancer (EOC) has the highest mortality rate of all gynecologic malignant tumors. Diagnosis of epithelial ovarian cancer (EOC) presents two main challenges. The first challenge is detecting low volume (prolactin receptor (PRLR) - a cell surface tyrosine kinase receptor that is over-expressed in moderate to high levels on > 98% of epithelial ovarian cancers. Upon binding of native ligands to PRLR, the ligand:PRLR complex is internalized by cells. By conjugating gadolinium-chelates, molecules normally used as contrast agents diagnostically, to human placental lactogen (hPL), a native ligand of PRLR, we show that MRI becomes highly sensitive and specific for detecting PRLR (+) tumors in a nude mouse model of EOC. We further establish the adaptability of this approach for fluorescence-based imaging techniques using an hPL conjugated Cy5.5 dye. We conclude that molecular imaging of PRLR with hPL-conjugated imaging agents can address the current challenges that limit EOC diagnosis.

  1. Circulating Haptoglobin Is an Independent Prognostic Factor in the Sera of Patients with Epithelial Ovarian Cancer*

    Science.gov (United States)

    Zhao, Changqing; Annamalai, Loganath; Guo, Changfa; Kothandaraman, Narasimhan; Koh, Stephen Chee Liang; Zhang, Huoming; Biswas, Arijit; Choolani, Mahesh

    2007-01-01

    Abstract OBJECTIVE This study was conducted to evaluate the prognostic significance of haptoglobin levels in the overall survival of patients presenting with various stages of epithelial ovarian cancer. MATERIALS AND METHODS We employed an in-house sandwich enzyme-linked immunosorbent assay method to determine the concentrations of preoperative haptoglobin and C-reactive protein (CRP) in sera samples obtained from 66 malignant tumors, 60 benign tumors, and 10 normal healthy women. RESULTS Levels of serum haptoglobin significantly correlated with tumor type (P < .001) and International Federation of Gynecology and Obstetrics stage (P < .05). A significant correlation was observed between clinical stage and patient survival (r = 5.99, P = .026). Our data also indicated that elevated serum haptoglobin levels were associated with poor outcome for overall survival using both univariate and multivariate analyses (P = .048 and P = .036 respectively). Using Pearson's correlation, we have noted that serum CRP concentrations significantly correlated with haptoglobin levels (r2 = 0.22, P < .001). Immunohistochemical findings and Western blot analyses were compatible with sera levels of haptoglobin in which a higher intensity of staining occurred in late-stage epithelial ovarian cancers. CONCLUSION This study provides evidence that preoperative serum levels of haptoglobin could serve as an independent prognostic factor in patients presenting with epithelial ovarian cancer. PMID:17325738

  2. Circulating Haptoglobin Is an Independent Prognostic Factor in the Sera of Patients with Epithelial Ovarian Cancer

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    Changqing Zhao

    2007-01-01

    Full Text Available OBJECTIVE: This study was conducted to evaluate the prognostic significance of haptoglobin levels in the overall survival of patients presenting with various stages of epithelial ovarian cancer. MATERIALS AND METHODS: We employed an in-house sandwich enzyme-linked immunosorbent assay method to determine the concentrations of preoperative haptoglobin and C-reactive protein (CRP in sera samples obtained from 66 malignant tumors, 60 benign tumors, and 10 normal healthy women. RESULTS: Levels of serum haptoglobin significantly correlated with tumor type (P < .001 and International Federation of Gynecology and Obstetrics stage (P < .05. A significant correlation was observed between clinical stage and patient survival (r = 5.99, P = .026. Our data also indicated that elevated serum haptoglobin levels were associated with poor outcome for overall survival using both univariate and multivariate analyses (P = .048 and P = .036 respectively. Using Pearson's correlation, we have noted that serum CRP concentrations significantly correlated with haptoglobin levels (r2 = 0.22, P < .001. Immunohistochemical findings and Western blot analyses were compatible with sera levels of haptoglobin in which a higher intensity of staining occurred in late-stage epithelial ovarian cancers. CONCLUSION: This study provides evidence that preoperative serum levels of haptoglobin could serve as an independent prognostic factor in patients presenting with epithelial ovarian cancer.

  3. Quality of pathology reports for advanced ovarian cancer

    DEFF Research Database (Denmark)

    Verleye, Leen; Ottevanger, Petronella B; Kristensen, Gunnar B

    2011-01-01

    To assess the quality of surgical pathology reports of advanced stage ovarian, fallopian tube and primary peritoneal cancer. This quality assurance project was performed within the EORTC-GCG 55971/NCIC-CTG OV13 study comparing primary debulking surgery followed by chemotherapy with neoadjuvant...

  4. Microarray-based oncogenic pathway profiling in advanced serous papillary ovarian carcinoma.

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    Xuan Bich Trinh

    Full Text Available INTRODUCTION: The identification of specific targets for treatment of ovarian cancer patients remains a challenge. The objective of this study is the analysis of oncogenic pathways in ovarian cancer and their relation with clinical outcome. METHODOLOGY: A meta-analysis of 6 gene expression datasets was done for oncogenic pathway activation scores: AKT, β-Catenin, BRCA, E2F1, EGFR, ER, HER2, INFα, INFγ, MYC, p53, p63, PI3K, PR, RAS, SRC, STAT3, TNFα, and TGFβ and VEGF-A. Advanced serous papillary tumours from uniformly treated patients were selected (N = 464 to find differences independent from stage-, histology- and treatment biases. Survival and correlations with documented prognostic signatures (wound healing response signature WHR/genomic grade index GGI/invasiveness gene signature IGS were analysed. RESULTS: The GGI, WHR, IGS score were unexpectedly increased in chemosensitive versus chemoresistant patients. PR and RAS activation score were associated with survival outcome (p = 0.002;p = 0.004. Increased activations of β-Catenin (p = 0.0009, E2F1 (p = 0.005, PI3K (p = 0.003 and p63 (p = 0.05 were associated with more favourable clinical outcome and were consistently correlated with three prognostic gene signatures. CONCLUSIONS: Oncogenic pathway profiling of advanced serous ovarian tumours revealed that increased β-Catenin, E2F1, p63, PI3K, PR and RAS-pathway activation scores were significantly associated with favourable clinical outcome. WHR, GGI and IGS scores were unexpectedly increased in chemosensitive tumours. Earlier studies have shown that WHR, GGI and IGS are strongly associated with proliferation and that high-proliferative ovarian tumours are more chemosensitive. These findings may indicate opposite confounding of prognostic versus predictive factors when studying biomarkers in epithelial ovarian cancer.

  5. Management of epithelial ovarian cancer from diagnosis to restaging: an overview of the role of imaging techniques with particular regard to the contribution of 18F-FDG PET/CT.

    Science.gov (United States)

    Musto, Alessandra; Grassetto, Gaia; Marzola, Maria Cristina; Rampin, Lucia; Chondrogiannis, Sotirios; Maffione, Anna Margherita; Colletti, Patrick M; Perkins, Alan C; Fagioli, Giorgio; Rubello, Domenico

    2014-06-01

    Epithelial ovarian carcinoma is a major form of cancer affecting women in the western world. The silent nature of this disease results in late presentation at an advanced stage in many patients. It is therefore important to assess the role of imaging techniques in the management of these patients. This article presents a review of the literature on the role of (18)F-FDG-PET/CT in the different stages of management of epithelial ovarian cancer. Moreover, a comparison with other imaging techniques has been made and the relationship between (18)F-PET/CT and the assay of serum CA-125 levels has been discussed.

  6. Epithelial-Mesenchymal Transition (EMT) Gene Variants and Epithelial Ovarian Cancer (EOC) Risk

    DEFF Research Database (Denmark)

    Amankwah, Ernest K.; Lin, Hui-Yi; Tyrer, Jonathan P.

    2015-01-01

    Epithelial-mesenchymal transition (EMT) is a process whereby epithelial cells assume mesenchymal characteristics to facilitate cancer metastasis. However, EMT also contributes to the initiation and development of primary tumors. Prior studies that explored the hypothesis that EMT gene variants co...

  7. Elevated levels of circulating microRNA-200 family members correlate with serous epithelial ovarian cancer

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    Kan Casina WS

    2012-12-01

    Full Text Available Abstract Background There is a critical need for improved diagnostic markers for high grade serous epithelial ovarian cancer (SEOC. MicroRNAs are stable in the circulation and may have utility as biomarkers of malignancy. We investigated whether levels of serum microRNA could discriminate women with high-grade SEOC from age matched healthy volunteers. Methods To identify microRNA of interest, microRNA expression profiling was performed on 4 SEOC cell lines and normal human ovarian surface epithelial cells. Total RNA was extracted from 500 μL aliquots of serum collected from patients with SEOC (n = 28 and age-matched healthy donors (n = 28. Serum microRNA levels were assessed by quantitative RT-PCR following preamplification. Results microRNA (miR-182, miR-200a, miR-200b and miR-200c were highly overexpressed in the SEOC cell lines relative to normal human ovarian surface epithelial cells and were assessed in RNA extracted from serum as candidate biomarkers. miR-103, miR-92a and miR -638 had relatively invariant expression across all ovarian cell lines, and with small-nucleolar C/D box 48 (RNU48 were assessed in RNA extracted from serum as candidate endogenous normalizers. No correlation between serum levels and age were observed (age range 30-79 years for any of these microRNA or RNU48. Individually, miR-200a, miR-200b and miR-200c normalized to serum volume and miR-103 were significantly higher in serum of the SEOC cohort (P  Conclusions We identified serum microRNAs able to discriminate patients with high grade SEOC from age-matched healthy controls. The addition of these microRNAs to current testing regimes may improve diagnosis for women with SEOC.

  8. Expressions of beta-catenin, APC Protein, C-myc and Cyclin D1 in Ovarian Epithelial Tumor and Their Implication

    Institute of Scientific and Technical Information of China (English)

    LIN Xiao; LI Yu; MI Can

    2007-01-01

    Objective: To investigate the expressions of beta-catenin, protein APC (adenomatous polyposis coli protein), c-myc and cyclin D1 and their implication in ovarian epithelial tumor. Methods: Immunohistochemical staining with SP method was conducted to identify the expressions of beta-catenin, APC protein, c-myc and cyclin D1 in ovarian epithelial tumor in 48 cases. Results: The abnormal expression rate of beta-catenin in malignant and borderline ovarian epithelial tumors was higher than that in benign epithelial tumors (P<0.01). The expression rates of c-myc and cyclin-D1 in ovarian malignant and borderline epithelial tumors were higher than those in benign epithelial tumors too(P<0.05). The prevalence of APC protein positive expression in benign epithelial tumors were significantly greater than that in malignant epithelial tumors (P<0.05). A significant negative correlation was found between beta-catenin and APC protein in ovarian epithelial tumors; while a significant positive correlation was found between beta-catenin, c-myc and cyclin-D1 in ovarian epithelial tumor (P<0.05). Conclusion: The abnormal expressions of Beta-catenin, APC protein, c-myc and cyclin-D1 might be used to indicate the malignance transform of ovarian epithelial tumors.

  9. Heterogeneity of the Mac-1 expression on peripheral blood neutrophils in patients with different types of epithelial ovarian cancer.

    Science.gov (United States)

    Bednarska, Katarzyna; Klink, Magdalena; Wilczyński, Jacek R; Szyłło, Krzysztof; Malinowski, Andrzej; Sułowska, Zofia; Nowak, Marek

    2016-02-01

    The expression level of Mac-1 on the surface of neutrophils is an important indicator of neutrophil activation. Under pathological conditions, Mac-1 is believed a key adhesion molecule that facilitates cancer progression and mediates the adhesion of tumour cells to the endothelium of blood vessels. Our previous findings indicated that circulating peripheral blood neutrophils in patients with advanced epithelial ovarian cancer (EOC) expressed enhanced levels of Mac-1, which was functionally associated with an increased adhesive function of neutrophils. The objective of the current study was to analyse whether the value of individual components of the differential white cell count, including the neutrophil and lymphocyte ratios, which are markers of blood neutrophil activation, might be associated with certain types of ovarian cancer. We showed the increase in Mac-1 expression along with a parallel decrease of L-selectin and PSGL-1 on peripheral blood neutrophils of patients with EOC of early and advanced FIGO stages, which indicates an activated state of neutrophils in comparison to neutrophils of individuals without cancer. Despite a significant difference between Mac-1 expression in patients with and without cancer, a dramatic increase in Mac-1 expression was observed in the blood of patients with undifferentiated carcinomas compared with patients with other histological types of EOC. Moreover, the expression level of Mac-1 correlated with the number of neutrophils in patients with serous, endometrioid and undifferentiated EOC. The results of an ROC analysis demonstrated that the patients with the undifferentiated type of EOC form a distinct group with regard to Mac-1 expression on blood neutrophils. The results suggested a diverse biological cadre of immune cells in patients with undifferentiated ovarian carcinomas compared with patients with other histological types of EOC.

  10. Adipose-derived mesenchymal stem cells promote cell proliferation and invasion of epithelial ovarian cancer

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    Chu, Yijing; Tang, Huijuan; Guo, Yan; Guo, Jing; Huang, Bangxing; Fang, Fang; Cai, Jing, E-mail: caijingmmm@hotmail.com; Wang, Zehua, E-mail: zehuawang@163.net

    2015-09-10

    Adipose-derived mesenchymal stem cell (ADSC) is an important component of tumor microenvironment. However, whether ADSCs have a hand in ovarian cancer progression remains unclear. In this study, we investigated the impact of human ADSCs derived from the omentum of normal donors on human epithelial ovarian cancer (EOC) cells in vitro and in vivo. Direct and indirect co-culture models including ADSCs and human EOC cell lines were established and the effects of ADSCs on EOC cell proliferation were evaluated by EdU incorporation and flow cytometry. Transwell migration assays and detection of MMPs were performed to assess the invasion activity of EOC cells in vitro. Mouse models were established by intraperitoneal injection of EOC cells with or without concomitant ADSCs to investigate the role of ADSCs in tumor progression in vivo. We found that ADSCs significantly promoted proliferation and invasion of EOC cells in both direct and indirect co-culture assays. In addition, after co-culture with ADSCs, EOC cells secreted higher levels of matrix metalloproteinases (MMPs), and inhibition of MMP2 and MMP9 partially relieved the tumor-promoting effects of ADSCs in vitro. In mouse xenograft models, we confirmed that ADSCs promoted EOC growth and metastasis and elevated the expression of MMP2 and MMP9. Our findings indicate that omental ADSCs play a promotive role during ovarian cancer progression. - Highlights: • Omental adipose derived stem cells enhanced growth and invasion properties of ovarian cancer cells. • Adipose derived stem cells promoted the growth and metastasis of ovarian cancer in mice models. • Adipose derived stem cells promoted MMPs expression and secretion of ovarian cancer cells. • Elevated MMPs mediated the tumor promoting effects of ADSCs.

  11. The role of the breast cancer susceptibility gene 1 (BRCA1 in sporadic epithelial ovarian cancer

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    Mueller Christopher R

    2003-10-01

    Full Text Available Abstract Mutations within the BRCA1 tumor suppressor gene occur frequently in familial epithelial ovarian carcinomas but they are a rare event in the much more prevalent sporadic form of the disease. However, decreased BRCA1 expression occurs frequently in sporadic tumors, and the magnitude of this decrease has been correlated with increased disease progression. The near absence of somatic mutations consequently suggests that there are alternative mechanisms that may contribute to the observed loss of BRCA1 in sporadic tumors. Indeed, both allelic loss at the BRCA1 locus and epigenetic hypermethylation of the BRCA1 promoter play an important role in BRCA1 down-regulation; yet these mechanisms alone or in combination do not always account for the reduced BRCA1 expression. Alternatively, misregulation of specific upstream factors that control BRCA1 transcription may be a crucial means by which BRCA1 is lost. Therefore, determining how regulators of BRCA1 expression may be co-opted during sporadic ovarian tumorigenesis will lead to a better understanding of ovarian cancer etiology and it may help foster the future development of novel therapeutic strategies aimed at halting ovarian tumor progression.

  12. Serum Anti-Müllerian Hormone Levels in Patients with Epithelial Ovarian Cancer

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    Pawel Walentowicz

    2013-01-01

    Full Text Available Objectives. The aim of our study was to examine serum anti-Müllerian hormone (AMH concentration in ovarian cancer patients in relation to clinicopathological features, such as a pathological subtype of the tumor, (FIGO stage, grading, and overall 5-year survival. Material and Methods. We enrolled 72 epithelial ovarian cancer patients in our study, aged 45–79 years, who underwent optimal cytoreductive surgery. In all patients, serum AMH concentration was measured using a two-step sandwich type enzyme immunoassay before surgery. As a reference value for women over 45 years we accepted anti-Müllerian hormone concentration below 1 ng/mL. Results. In the whole group of patients with ovarian cancer, median serum concentration of AMH was 0.07 (0.0–0.37 ng/mL, whereas in the group of those with positive AMH values (≥0.14 ng/mL it was 0.31 (0.15–0.73 ng/mL. No significant correlation was found between serum AMH levels and FIGO stage, histological subtype, or grading (. The analysis of five-year survival rate related to AMH levels showed no statistically significant differences. There were no differences in survival rates between patients with positive or negative serum AMH levels. Conclusion. Measurement of serum anti-Müllerian hormone levels was not useful in predicting clinicopathological features and survival in patients with ovarian cancer.

  13. PFTK1 regulates cell proliferation, migration and invasion in epithelial ovarian cancer.

    Science.gov (United States)

    Zhang, Weiwei; Liu, Rong; Tang, Chunhui; Xi, Qinghua; Lu, Shumin; Chen, Wenjuan; Zhu, Lianxin; Cheng, Jialin; Chen, Yannan; Wang, Wei; Zhong, Jianxin; Deng, Yan

    2016-04-01

    PFTK1, also named Cyclin-Dependent Kinase 14 (CDK14), is a member of the cell division cycle 2 (CDC2)-related protein kinase family. It is a serine/threonine-protein kinase involved in the regulation of cell cycle progression and cell proliferation. In this study, we investigated the role of PFTK1 in epithelial ovarian cancer (EOC) development. The expression of PFTK1 was detected by Western blot and immunohistochemistry staining, both of which demonstrated that PFTK1 was overexpressed in EOC tissues and cells. Statistical analysis showed the expression of PFTK1 was associated with multiple clinicopathological factors, including tumor grade, FIGO stage, lymph node metastatis, Ki-67 expression and predicted a poor prognosis of EOC patients. With in vitro studies we found that PFTK1 expression was decreased in serum-starved ovarian cancer cells, and progressively increased after serum-re-feeding. Knocking PFTK1 down by small interfering RNA (siRNA) significantly inhibited ovarian cancer cell proliferation, migration and invasion. Taken together, our study suggested that PFTK1 played an important role in ovarian cancer development.

  14. Recreational physical inactivity and mortality in women with invasive epithelial ovarian cancer

    DEFF Research Database (Denmark)

    Cannioto, Rikki A; LaMonte, Michael J; Kelemen, Linda E

    2016-01-01

    and mortality. METHODS: Participants included 6806 women with a primary diagnosis of invasive EOC. In accordance with the Physical Activity Guidelines for Americans, women reporting no regular, weekly recreational physical activity were classified as inactive. We utilised Cox proportional hazard models......BACKGROUND: Little is known about modifiable behaviours that may be associated with epithelial ovarian cancer (EOC) survival. We conducted a pooled analysis of 12 studies from the Ovarian Cancer Association Consortium to investigate the association between pre-diagnostic physical inactivity.......12-1.33) further adjustment for residual disease, respectively. CONCLUSION: In this large pooled analysis, lack of recreational physical activity was associated with increased mortality among women with invasive EOC....

  15. Anthropometric measures and epithelial ovarian cancer risk in the European Prospective Investigation into Cancer and Nutrition.

    Science.gov (United States)

    Lahmann, Petra H; Cust, Anne E; Friedenreich, Christine M; Schulz, Mandy; Lukanova, Annekatrin; Kaaks, Rudolf; Lundin, Eva; Tjønneland, Anne; Halkjaer, Jytte; Severinsen, Marianne Tang; Overvad, Kim; Fournier, Agnès; Chabbert-Buffet, Nathalie; Clavel-Chapelon, Françoise; Dossus, Laure; Pischon, Tobias; Boeing, Heiner; Trichopoulou, Antonia; Lagiou, Pagona; Naska, Androniki; Palli, Domenico; Grioni, Sara; Mattiello, Amalia; Tumino, Rosario; Sacerdote, Carlotta; Redondo, María-Luisa; Jakszyn, Paula; Sánchez, María-José; Tormo, María-José; Ardanaz, Eva; Arriola, Larraitz; Manjer, Jonas; Jirström, Karin; Bueno-de-Mesquita, H Bas; May, Anne M; Peeters, Petra H M; Onland-Moret, N Charlotte; Bingham, Sheila; Khaw, Kay-Tee; Allen, Naomi E; Spencer, Elizabeth; Rinaldi, Sabina; Slimani, Nadia; Chajes, Véronique; Michaud, Dominique; Norat, Teresa; Riboli, Elio

    2010-05-15

    We examined the associations of measured anthropometric factors, including general and central adiposity and height, with ovarian cancer risk. We also investigated these associations by menopausal status and for specific histological subtypes. Among 226,798 women in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, there were 611 incident cases of primary, malignant, epithelial ovarian cancer diagnosed during a mean 8.9 years of follow-up. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusted for potential confounders. Compared to women with body mass index (BMI) or = 30 kg/m2) was associated with excess ovarian cancer risk for all women combined (HR = 1.33, 95% CI = 1.05-1.68; p(trend) = 0.02) and postmenopausal women (HR = 1.59, 95% CI = 1.20-2.10; p(trend) = 0.001), but the association was weaker for premenopausal women (HR = 1.16, 95% CI = 0.65-2.06; p(trend) = 0.65). Neither height or weight gain, nor BMI-adjusted measures of fat distribution assessed by waist circumference, waist-hip ratio (WHR) or hip circumference were associated with overall risk. WHR was related to increased risk of mucinous tumors (BMI-adjusted HR per 0.05 unit increment = 1.17, 95% CI = 1.00-1.38). For all women combined, no other significant associations with risk were observed for specific histological subtypes. This large, prospective study provides evidence that obesity is an important modifiable risk factor for epithelial ovarian cancer, particularly among postmenopausal women.

  16. TAZ Mediates Lysophosphatidic Acid-Induced Migration and Proliferation of Epithelial Ovarian Cancer Cells

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    Geun Ok Jeong

    2013-07-01

    Full Text Available Background: Transcriptional co-activator with PDZ-binding motif (TAZ, a downstream effector of the Hippo pathway, has been reported to regulate organ size, tissue homeostasis, and tumorigenesis by acting as a transcriptional co-activator. Lysophosphatidic acid (LPA is a bioactive lipid implicated in tumorigenesis and metastasis of ovarian cancer through activation of G protein-coupled receptors. However, the involvement of TAZ in LPA-induced tumorigenesis of ovarian cancer has not been elucidated. Methods: In order to demonstrate the role of TAZ in LPA-stimulated tumorigenesis, the effects of LPA on TAZ expression and cell migration were determined by Western blotting and chemotaxis analyses in R182 human epithelial ovarian cancer cells. Results and Conclusion: Treatment of R182 cells with the LPA receptor inhibitor Ki16425 blocked LPA-induced cell migration. In addition, transfection of R182 cells with small interfering RNA specific for LPA receptor 1 resulted in abrogation of LPA-stimulated cell migration. LPA induced phosphorylation of ERK and p38 MAP kinase in R182 cells and pretreatment of cells with the MEK-ERK pathway inhibitor U0126, but not the p38 MAPK inhibitor SB202190, resulted in abrogation of LPA-induced cell migration. Pretreatment of R182 cells with U0126 attenuated LPA-induced mRNA levels of TAZ and its transcriptional target genes, such as CTGF and CYR61, without affecting phosphorylation level of YAP. These results suggest that MEK-ERK pathway plays a key role in LPA-induced cell migration and mRNA expression of TAZ in R182 cells, without affecting stability of TAZ protein. In addition, small interfering RNA-mediated silencing of TAZ expression attenuated LPA-stimulated migration of R182 cells. These results suggest that TAZ plays a key role in LPA-stimulated migration of epithelial ovarian cancer cells.

  17. Total and individual antioxidant intake and risk of epithelial ovarian cancer

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    Gifkins Dina

    2012-06-01

    Full Text Available Abstract Background Limiting oxidative stress to the ovarian epithelium has been proposed as a first-line defense against ovarian cancer. Although evidence for an association between individual dietary antioxidant intake and ovarian cancer risk is conflicting, the combined evidence suggests a modest inverse association. Our study aimed to evaluate the association between total antioxidant capacity (TAC and individual antioxidant intakes (vitamin C, vitamin E, beta-carotene, selenium, lutein, and lycopene and ovarian cancer risk. Methods We conducted a population-based case–control study in New Jersey. Cases were women ages 21 years and older with newly diagnosed epithelial ovarian cancer who resided in six counties of New Jersey. Controls were women in the same age range who resided in the same geographic area. A total of 205 ovarian cancer cases and 390 controls were included. Dietary intake was ascertained using the Block food frequency questionnaire (FFQ, and TAC indices were constructed by linking FFQ-derived estimates to two standardized antioxidant capacity databases, the USDA Oxygen Radical Absorbance Capacity (ORAC Database, and the University of Olso’s Antioxidant Food Database. Multivariate logistic regression models were used to calculate odds ratios and 95 % confidence intervals while controlling for major ovarian cancer risk factors. Results We found a strong inverse association with selenium from food sources (OR: 0.41; 95 % CI: 0.20-0.85, for the highest vs. lowest tertile of dietary selenium intake. However, there was little evidence of an association with dietary TAC or the others individual antioxidants. In contrast, compared to non-users, supplement users had significant increased risk for all micronutrients, but no statistically significant increased risk was observed for combined intake from foods and supplements of any of these antioxidants. Conclusions This study found an inverse association between selenium

  18. Detection of Laminin in Serum and Ascites from Patients with Epithelial Ovarian Tumor

    Institute of Scientific and Technical Information of China (English)

    初永丽; 杨元先; 林美华; 王泽华

    2002-01-01

    The change in serum laminin (LN) level and its clinical significance in epithelial ovarian tumor were investigated. The LN levels in serum and ascites samples from 69 patients with epithelial ovarian tumor and 42 cases as control group before and after operation were analyzed by radioimmunoassay. The results showed that the serum LN levels in the patients with malignant tumors (157. 85 ± 14.37 ng/ml) were significantly higher than that in the control group (125.14 47.03ng/ml) and in the patients with benign tumors (128. 36±8. 75 ng/ml)(both P<0. 01) before operation. The serum LN levels in the malignant group were decreased significantly after operation as compared with those before operation (P<0. 05). The serum LN levels in low-differentiated tumors was higher than those in moderate-differentiated tumors and high-differentiated tumors (P<0. 05). The LN levels in ascites (172.94±15.26 ng/ml) was significantly higher than in serum (161.34±6.59ng/ml) (P<0. 05) in malignant tumors. The serum LN levels in the patients with lymph node metastasis (165.41± 19.91 ng/ml) was obviously higher than those without lymph node metastasis (152.35±10. 34 ng/ml)(P<0. 05). It was concluded that LN levels in serum and acistes were remarkably increased in malignant epithelial ovarian tumors, suggesting that LN might be one of important diameters reflecting tumor biological characteristics.

  19. PHASE Ⅱ STUDY OF GEMCITABINE COMBINED WITH PLATINUM CHEMOTHERAPY FOR RECURRENT EPITHELIAL OVARIAN CANCER

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective To evaluate the anti-tumor effect and toxicity of gemcitabine combined with platinum chemotherapy on recurrent epithelial ovarian cancer.Methods Phase Ⅱ study of gemcitabine combined with platinum chemotherapy was carried out in 22 patients with recurrent epithelial ovarian cancer. Median age of patients was 50. 5 years old. Seven patients were platinum-sensitive and 15 patients were platinum-resistant or -refractor. All patients received gemcitabine combined with carboplatin or oxaliplatin chemotherapy. Patients' response rate (RR) and toxicity of gemcitabine combined with platinum chemotherapy were evaluated.Results A total of 98 gemcitabine-based chemotherapy cycles were performed. Total RR was 36.4%, RR of platinum-sensitive patients was 4/7 and platinum-resistant and -refractory patients was 4/15. The estimated median survival time was 10. 0 months (95% CI: 7.0-13.0) after initiation of gemcitabine combined with platinum chemotherapy.There was no significant difference in survival time between platinum-resistant/refractory group and platinum-sensitive group (P = 0. 061 ). Side effects of gemcitabine combined with platinum chemotherapy were observed in 81.8 % of patients. Grade Ⅱ/Ⅲ anemia (54.5%) and grade Ⅲ/Ⅳ neutropenia (54.5%) were most common toxicities. Ten (45.5%) patients had to delay their chemotherapy cycles or reduce the dose of chemotherapeutic drugs because of the severe side effects. Fourteen (63.6%) patients received granulocyte colony-stimulating factor to relieve neutropenia,and 8 (36. 4% ) patients received component blood transfusion to treat anemia or thrombocytopenia. There was no treatment-associated death.Conclusion Gemcitabine combined with platinum chemotherapy appears to be an effective and well-tolerant treatment for recurrent epithelial ovarian cancer, including platinum-resistant or -refractory diseases.

  20. Overexpression of glucose transporter-1 (GLUT-1) predicts poor prognosis in epithelial ovarian cancer.

    Science.gov (United States)

    Cho, Hanbyoul; Lee, You Sun; Kim, Julie; Chung, Joon-Yong; Kim, Jae-Hoon

    2013-11-01

    Illumina microarray was used to identify differentially expressed genes in three epithelial ovarian cancer (EOC) cells. To validate the microarray data, mRNA and protein level of glucose transporter-1 (GLUT-1) was examined. GLUT-1 had an EOC/normal cells ratio of 5.51 based on microarray. Real-time PCR and immunohistochemistry demonstrated that GLUT-1 expression was significantly increased in EOC (p = .029 and p GLUT-1 overexpression (HR = 4.80, p = .027) and lymph node metastases (HR = 8.35, p = .016) conferred a significantly worse overall survival. In conclusion, GLUT-1 expression is remarkably upregulated in EOC and predicts a poor overall survival.

  1. The Prognostic Value of BRCA1 and PARP Expression in Epithelial Ovarian Carcinoma

    DEFF Research Database (Denmark)

    Hjortkjær, Mette; Waldstrøm, Marianne; Jakobsen, Anders

    2017-01-01

    BRCA1/2 mutation status in epithelial ovarian cancer (EOC) presently relies on genetic testing which is resource consuming. Immunohistochemistry is cheap, fairly reproducible, and may identify gene product alterations due to both germline and somatic mutations and other defects along the BRCA gene...... tissue from 170 patients with EOC was stained immunohistochemically with BRCA1 and PARP antibodies. Semiquantitative analyses were performed to determine loss of, equivocal, and retained BRCA1 and high versus low PARP protein expression. These parameters were analyzed for relation with patient...

  2. High-risk HPV is not associated with epithelial ovarian cancer in a Caucasian population

    DEFF Research Database (Denmark)

    Ingerslev, Kasper Hjorth; Hogdall, Estrid; Skovrider-Ruminski, Wojciech

    2016-01-01

    BACKGROUND: High-risk human papillomavirus (HPV) has been suspected to play a role in the carcinogenesis of epithelial ovarian cancer (EOC). However, results from previous studies are conflicting. In most of these studies, the number of tissue samples was small. The current study was therefore...... undertaken to examine the prevalence of high-risk HPV DNA in EOC in a large series of patients. METHOD: Formalin-fixed, paraffin-imbedded tumor tissue samples from 198 cases consecutively included in the Danish Pelvic Mass Study were analyzed. The material included 163 serous adenocarcinomas, 15 endometrioid...

  3. Expression of Vascular Endothelial Growth Factor-C and Vascular Endothelial Growth Factor Receptor-3 in Ovarian Epithelial Tumors

    Institute of Scientific and Technical Information of China (English)

    FU Xiao-yan; DING Ming-xing; ZHANG Ning; LIN Xing-qiu; LI Ji-cheng

    2007-01-01

    Objective: To explore the role of vascular endothelial growth factor-C (VEGF-C) in the process of angiogenesis, lymphangiogenesis and lymphatic metastasis in epithelial ovarian tumors. Methods: In situ hybridization and immunohistochemical staining for VEGF-C were performed in 30 epithelial ovarian carcinomas, 9 borderline tumors and 26 benign tumors. Endothelial cells were immunostained with anti-VEGFR-3 pAb and anti-CD31 mAb, and VEGFR-3 positive vessels and microvessel density (MVD) were assessed by image analysis. Results: VEGF-C mRNA and protein expression were detected in cytoplasm of carcinoma cells. VEGF-C mRNA and protein expression in ovarian epithelial carcinomas were significantly higher than those in borderline tumors and benign tumors (P<0.05 or P<0.01). In ovarian epithelial carcinomas, VEGF-C protein expression, VEGFR-3 positive vessels and MVD were significantly higher in the cases of clinical stage Ⅲ-Ⅳ and with lymph node metastasis than those of clinical stage Ⅰ-Ⅱ and without lymph node metastasis respectively (P<0.05 or P<0.01). VEGFR-3 positive vessels and MVD were significantly higher in VEGF-C protein positive tumors than negative tumors (P<0.05). VEGFR-3 positive vessels was significantly correlated with MVD(P<0.01). Conclusion: VEGF-C might play a role in lymphatic metastasis via lymphangiogenesis and angiogenesis in epithelial ovarian tumors, and VBEGF-C could be used as a biologic marker of metastasis in ovarian epithelial tumors.

  4. The RUNX1 transcription factor is expressed in serous epithelial ovarian carcinoma and contributes to cell proliferation, migration and invasion

    Science.gov (United States)

    Keita, Mamadou; Bachvarova, Magdalena; Morin, Chantale; Plante, Marie; Gregoire, Jean; Renaud, Marie-Claude; Sebastianelli, Alexandra; Trinh, Xuan Bich; Bachvarov, Dimcho

    2013-01-01

    Previously, we have identified the RUNX1 gene as hypomethylated and overexpressed in post-chemotherapy (CT) primary cultures derived from epithelial ovarian cancer (EOC) patients, when compared with primary cultures derived from matched primary (prior to CT) tumors. Here we show that RUNX1 displays a trend of hypomethylation, although not significant, in omental metastases compared with primary EOC tumors. Surprisingly, RUNX1 displayed significantly higher expression not only in metastatic tissue, but also in high-grade primary tumors and even in low malignant potential tumors. The RUNX1 expression levels were almost identical in primary tumors and omental metastases, suggesting that RUNX1 hypomethylation might have a limited impact on its overexpression in advanced (metastatic) stage of the disease. Knockdown of the RUNX1 expression in EOC cells led to sharp decrease of cell proliferation and induced G1 cell cycle arrest. Moreover, RUNX1 suppression significantly inhibited EOC cell migration and invasion. Gene expression profiling and consecutive network and pathway analyses confirmed these findings, as numerous genes and pathways known previously to be implicated in ovarian tumorigenesis, including EOC tumor invasion and metastasis, were found to be downregulated upon RUNX1 suppression, while a number of pro-apoptotic genes and some EOC tumor suppressor genes were induced. Taken together, our data are indicative for a strong oncogenic potential of the RUNX1 gene in EOC progression and suggest that RUNX1 might be a novel EOC therapeutic target. Further studies are needed to more completely elucidate the functional implications of RUNX1 and other members of the RUNX gene family in ovarian tumorigenesis. PMID:23442798

  5. Aspirin, nonaspirin nonsteroidal anti-inflammatory drug, and acetaminophen use and risk of invasive epithelial ovarian cancer

    DEFF Research Database (Denmark)

    Trabert, Britton; Ness, Roberta B; Lo-Ciganic, Wei-Hsuan

    2014-01-01

    BACKGROUND: Regular aspirin use is associated with reduced risk of several malignancies. Epidemiologic studies analyzing aspirin, nonaspirin nonsteroidal anti-inflammatory drug (NSAID), and acetaminophen use and ovarian cancer risk have been inconclusive. METHODS: We analyzed pooled data from 12...... population-based case-control studies of ovarian cancer, including 7776 case patients and 11843 control subjects accrued between 1992 and 2007. Odds ratios (ORs) for associations of medication use with invasive epithelial ovarian cancer were estimated in individual studies using logistic regression...... and combined using random effects meta-analysis. Associations between frequency, dose, and duration of analgesic use and risk of ovarian cancer were also assessed. All statistical tests were two-sided. RESULTS: Aspirin use was associated with a reduced risk of ovarian cancer (OR = 0.91; 95% confidence interval...

  6. Effect of BSD 2000 deep thermotherapy plus chemotherapy in treatment of malignant seroperitoneum of advanced epithelial ovarian cancer patients with drug resistance%BSD2000相控阵聚焦热疗联合化疗治疗耐药性卵巢上皮癌患者恶性腹腔积液的效果

    Institute of Scientific and Technical Information of China (English)

    何朗; 孙永红; 文世民; 陈红

    2015-01-01

    目的 观察BSD 2000相控阵聚焦热疗联合化疗对耐药性卵巢上皮癌患者恶性腹腔积液的疗效.方法 36例耐药性卵巢上皮癌恶性腹腔积液患者按抽签法随机分为治疗组和对照组各18例,其中治疗组采用BSD 2000相控阵聚焦热疗+GT方案(吉西他滨1 000 mg/m2静脉滴注,第1、8天;紫杉醇80 mg/m2腹腔注射,第1、8天)化疗;对照组单独采用GT方案化疗.28 d为1个周期,2个周期后评价疗效、患者不良反应、Karnofsky评分、中位生存时间.结果 治疗组有效率(RR)高于对照组[55.6%(10/18)比22.2%(4/18),P<0.05],疾病控制率(DCR)亦高于对照组,但差异无统计学意义(P>0.05).两组不良反应类似,无Ⅲ~Ⅳ度不良反应发生.治疗组Karnofsky评分改善率高于对照组,差异无统计学意义(P>0.05).两组患者中位生存时间、生存率比较差异均无统计学意义(均P> 0.05).结论 BSD 2000相控阵聚焦热疗联合化疗可有效控制耐药性卵巢上皮癌患者恶性腹腔积液,改善患者生命质量,不良反应轻微.%Objective To observe the effect of BSD 2000 deep thermotherapy plus chemotherapy in treatment of malignant seroperitoneum of advanced epithelial ovarian cancer patients with drug resistance.Methods 36 advanced epithelial ovarian cancer patients with malignant seroperitoneum for drug resistance were randomly divided into two groups,trial group (18 cases) and control group (18 cases).Cases in trial group were treated with BSD 2000 deep thermotherapy plus GT regimen (gemcitabine 1 000 mg/m2 iv d1,d8,taxinol 80 mg/m2 ip d1,d8.28 days for a cycle),while control group with GT regimen alone.Effect,survival time (median) toxicity and Karnofsky score were evaluated after 2 cycles.Results Response rate (RR) was strongly higher in trial group compared with control group [55.6 % (10/18) vs 22.2 % (4/18),P < 0.05],the same to disease control rate (DCR),but there was not significant difference between two groups (P

  7. Palliative Care in Improving Quality of Life and Symptoms in Patients With Stage III-IV Pancreatic or Ovarian Cancer

    Science.gov (United States)

    2014-12-18

    Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Pancreatic Cancer; Stage III Pancreatic Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Pancreatic Cancer

  8. The MyD88+ phenotype is an adverse prognostic factor in epithelial ovarian cancer.

    LENUS (Irish Health Repository)

    d'Adhemar, Charles J

    2014-01-01

    The prognosis of epithelial ovarian cancer is poor in part due to the high frequency of chemoresistance. Recent evidence points to the Toll-like receptor-4 (TLR4), and particularly its adaptor protein MyD88, as one potential mediator of this resistance. This study aims to provide further evidence that MyD88 positive cancer cells are clinically significant, stem-like and reproducibly detectable for the purposes of prognostic stratification. Expression of TLR4 and MyD88 was assessed immunohistochemically in 198 paraffin-embedded ovarian tissues and in an embryonal carcinoma model of cancer stemness. In parallel, expression of TLR4 and MyD88 mRNA and regulatory microRNAs (miR-21 and miR-146a) was assessed, as well as in a series of chemosensitive and resistant cancer cells lines. Functional analysis of the pathway was assessed in chemoresistant SKOV-3 ovarian cancer cells. TLR4 and MyD88 expression can be reproducibly assessed via immunohistochemistry using a semi-quantitative scoring system. TLR4 expression was present in all ovarian epithelium (normal and neoplastic), whereas MyD88 was restricted to neoplastic cells, independent of tumour grade and associated with reduced progression-free and overall survival, in an immunohistological specific subset of serous carcinomas, p<0.05. MiR-21 and miR-146a expression was significantly increased in MyD88 negative cancers (p<0.05), indicating their participation in regulation. Significant alterations in MyD88 mRNA expression were observed between chemosensitive and chemoresistant cells and tissue. Knockdown of TLR4 in SKOV-3 ovarian cells recovered chemosensitivity. Knockdown of MyD88 alone did not. MyD88 expression was down-regulated in differentiated embryonal carcinoma (NTera2) cells, supporting the MyD88+ cancer stem cell hypothesis. Our findings demonstrate that expression of MyD88 is associated with significantly reduced patient survival and altered microRNA levels and suggest an intact\\/functioning TLR4\\/MyD88

  9. The MyD88+ phenotype is an adverse prognostic factor in epithelial ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Charles J d'Adhemar

    Full Text Available The prognosis of epithelial ovarian cancer is poor in part due to the high frequency of chemoresistance. Recent evidence points to the Toll-like receptor-4 (TLR4, and particularly its adaptor protein MyD88, as one potential mediator of this resistance. This study aims to provide further evidence that MyD88 positive cancer cells are clinically significant, stem-like and reproducibly detectable for the purposes of prognostic stratification. Expression of TLR4 and MyD88 was assessed immunohistochemically in 198 paraffin-embedded ovarian tissues and in an embryonal carcinoma model of cancer stemness. In parallel, expression of TLR4 and MyD88 mRNA and regulatory microRNAs (miR-21 and miR-146a was assessed, as well as in a series of chemosensitive and resistant cancer cells lines. Functional analysis of the pathway was assessed in chemoresistant SKOV-3 ovarian cancer cells. TLR4 and MyD88 expression can be reproducibly assessed via immunohistochemistry using a semi-quantitative scoring system. TLR4 expression was present in all ovarian epithelium (normal and neoplastic, whereas MyD88 was restricted to neoplastic cells, independent of tumour grade and associated with reduced progression-free and overall survival, in an immunohistological specific subset of serous carcinomas, p<0.05. MiR-21 and miR-146a expression was significantly increased in MyD88 negative cancers (p<0.05, indicating their participation in regulation. Significant alterations in MyD88 mRNA expression were observed between chemosensitive and chemoresistant cells and tissue. Knockdown of TLR4 in SKOV-3 ovarian cells recovered chemosensitivity. Knockdown of MyD88 alone did not. MyD88 expression was down-regulated in differentiated embryonal carcinoma (NTera2 cells, supporting the MyD88+ cancer stem cell hypothesis. Our findings demonstrate that expression of MyD88 is associated with significantly reduced patient survival and altered microRNA levels and suggest an intact/functioning TLR4

  10. Leukocyte-associated immunoglobulin-like receptor-1 expressed in epithelial ovarian cancer cells and involved in cell proliferation and invasion

    Energy Technology Data Exchange (ETDEWEB)

    Cao, Qizhi [Department of Immunology, Binzhou Medical University, Yantai (China); Fu, Aili [Department of Immunology, Binzhou Medical University, Yantai (China); The People' s Liberation Army 107 Hospital, Affiliated Hospital of Bin Zhou Medical University, Yantai (China); Yang, Shude [Institute of Fungi Science and Technology, Ludong University, Yantai (China); He, Xiaoli; Wang, Yue; Zhang, Xiaoshu; Zhou, Jiadi; Luan, Xiying [Department of Immunology, Binzhou Medical University, Yantai (China); Yu, Wenzheng, E-mail: bzywz2009@163.com [Department of Hemotology, The Hospital Affiliated Binzhou Medical University, Binzhou (China); Xue, Jiangnan, E-mail: xuejinagnan@263.net [Department of Immunology, Binzhou Medical University, Yantai (China)

    2015-03-06

    Previous studies have shown that leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is expressed on most types of hamatopoietic cells and negatively regulate immune response, but the roles of LAIR-1 in tumor of the non-hematopoietic lineage have not been determined. Despite advances in therapy of epithelial ovarian cancer (EOC), many questions relating to EOC pathogenesis remain unanswered. The aim of this study was to investigate the clinical significance of LAIR-1 expression in EOC and explore the possible association between LAIR-1 and cancer. In this study, a tissue microarray containing 78 ovarian cancer cases was stained following a standard immunohistochemical protocol for LAIR-1 and the correlation of LAIR-1 expression with clinicopathologic features was assessed. LAIR-1 was detected to express in tumor cells of ovarian cancer tissues (73.1%) and EOC cell lines COC1 and HO8910, not in normal ovarian tissues. In addition, LAIR-1 expression correlates significantly with tumor grade (p = 0.004). Furthermore, down-regulation of LAIR-1 in HO8910 cells increased cell proliferation, colony formation and cell invasion. These data suggest that LAIR-1 has a relevant impact on EOC progression and may be helpful for a better understanding of molecular pathogenesis of cancer. - Highlights: • LAIR-1 is expressed in epithelial ovarian cancer cells. • LAIR-1 expression correlates significantly with tumor grade. • Down-regulation of LAIR-1 expression increased cell proliferation and invasion. • LAIR-1 may be a novel candidate for cancer diagnosis and therapy.

  11. Profile of pazopanib and its potential in the treatment of epithelial ovarian cancer

    Directory of Open Access Journals (Sweden)

    Davidson BA

    2014-03-01

    Full Text Available Brittany A Davidson, Angeles Alvarez Secord Division of Gynecologic Oncology, Duke Cancer Institute, Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC, USA Abstract: Epithelial ovarian cancer (EOC is the most lethal gynecological cancer. Recently, clinical trials have focused on novel antiangiogenic agents in combination with chemotherapy or alone in women with primary and recurrent ovarian cancer. Antiangiogenic agents include monoclonal antibodies, tyrosine-kinase inhibitors, and peptibodies. Many of these agents, including bevacizumab, pazopanib, nintedanib, cediranib, and trebananib, have been evaluated in randomized Phase III clinical trials, and all have demonstrated a progression-free survival (PFS benefit. Specifically, maintenance pazopanib was shown to improve PFS in women with newly diagnosed EOC. Pazopanib, an oral TKI, inhibits several kinase receptors, including those for vascular endothelial growth factor (-1,-2,-3, platelet-derived growth factor (-α and -β, and fibroblast growth factor. It also targets stem cell-factor receptor (c-kit, interleukin 2-inducible T-cell kinase, lymphocyte-specific protein tyrosine kinase, and colony-stimulating factor 1 receptor. Pazopanib has been investigated in several Phase II and III clinical trials, with results indicating a potential role in the management of EOC. This article provides an overview of pazopanib in the treatment of EOC. Keywords: pazopanib, antiangiogenic agents, ovarian carcinoma

  12. Prognostic value of preoperative intratumoral FDG uptake heterogeneity in patients with epithelial ovarian cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Maria; Kim, Hee Seung; Chung, Hyun Hoon; Kim, Jae-Weon; Park, Noh-Hyun; Song, Yong Sang [Seoul National University College of Medicine, Department of Obstetrics and Gynecology, Cancer Research Institute, Seoul (Korea, Republic of); Lee, Hyunjong; Cheon, Gi Jeong [Seoul National University College of Medicine, Department of Nuclear Medicine, Cancer Research Institute, Seoul (Korea, Republic of)

    2017-01-15

    To investigate the prognostic value of intratumoral FDG uptake heterogeneity (IFH) derived from PET/CT in patients with epithelial ovarian cancer (EOC). We retrospectively reviewed patients with pathologically proven epithelial ovarian cancer who underwent preoperative {sup 18}F-FDG PET/CT scans. PET/CT parameters such as maximum and average standardized uptake values (SUV{sub max} and SUV{sub avg}), sum of all metabolic tumour volume (MTV), cumulative total lesion glycolysis (TLG) and IFH were assessed. Regression analyses were used to identify clinicopathological and imaging variables associated with disease-free survival (DFS). Clinicopathological data were reviewed for 61 eligible patients. The median duration of DFS was 13 months (range, 6-26 months), and 18 (29.5 %) patients experienced recurrence. High IFH values were associated with tumour recurrence (P = 0.005, hazard ratio 4.504, 95 % CI 1.572-12.902). The Kaplan-Meier survival graphs showed that DFS significantly differed in groups categorized based on IFH (P = 0.002, log-rank test). Moreover, there were significant differences in DFS (P = 0.009) and IFH (P = 0.040) between patients with and without recurrence. Preoperative IFH measured by {sup 18}F-FDG PET/CT was significantly associated with EOC recurrence. FDG-based heterogeneity could be a useful and potential predicator of EOC recurrence before treatment. (orig.)

  13. Characterization of the specificity by immunohistology of a monoclonal antibody to a novel epithelial antigen of ovarian carcinomas.

    Science.gov (United States)

    Mariani-Costantini, R; Agresti, R; Colnaghi, M I; Ménard, S; Andreola, S; Rilke, F

    1985-08-01

    An immunohistological study, using the avidin-biotin-peroxidase complex method, was carried out to define the reactivity profile of a murine monoclonal antibody, MOv2, which recognizes a novel glycoprotidic antigen associated with ovarian epithelial tumors. Among the primary ovarian tumors tested, MOv2 immunostained 93% of mucinous and 75% of serous cystadenomas, 100% of mucinous, 81% of serous and 73% of endometrioid carcinomas. Undifferentiated and clear cell tumors revealed more limited reactivity with the antibody, whereas ovarian sex cord-stromal and germinal tumors were immunonegative. Positive reactions were also documented in omental metastases from primary ovarian carcinomas. No immunoreactivity was detected in normal ovarian epithelium, whereas the cells lining Walthard's nests adjacent to the fallopian tubes and a variety of normal epithelia were consistently immunolabeled. These included the lining epithelia of the gastrointestinal tract, bronchi and endocervix, and the epithelium of salivary, biliary and pancreatic ducts and sweat glands. To a lesser extent, positive reactions were detected in other surface epithelia, such as squamous and transitional epithelia. Among tumors other than ovarian, MOv2 consistently reacted with adenocarcinomas and squamous cell carcinomas from different sites, most notably breast, lung and gastrointestinal tract, and with transitional cell carcinomas. In contrast, no staining was demonstrated in non-epithelial malignancies. The antigen defined by MOv2 may be operationally useful as a marker of epithelial lineage in tumor histopathology. Its pattern of immunohistochemical distribution indicates that an antigenic phenotype shared by normal surface epithelia and non-ovarian carcinomas is strongly associated with common epithelial neoplasms of the ovaries.

  14. Recreational physical activity and epithelial ovarian cancer: a case-control study, systematic review, and meta-analysis.

    Science.gov (United States)

    Olsen, Catherine M; Bain, Christopher J; Jordan, Susan J; Nagle, Christina M; Green, Adèle C; Whiteman, David C; Webb, Penelope M

    2007-11-01

    It remains unclear whether physical activity is associated with epithelial ovarian cancer risk. We therefore examined the association between recreational physical activity and risk of ovarian cancer in a national population-based case-control study in Australia. We also systematically reviewed all the available evidence linking physical activity with ovarian cancer to provide the best summary estimate of the association. The case-control study included women ages 18 to 79 years with a new diagnosis of invasive (n=1,269) or borderline (n=311) epithelial ovarian cancer identified through a network of clinics, physicians, and state cancer registries throughout Australia. Controls (n=1,509) were randomly selected from the national electoral roll and were frequency matched to cases by age and state. For the systematic review, we identified eligible studies using Medline, the ISI Science Citation Index, and manual review of retrieved references, and included all case-control or cohort studies that permitted assessment of an association between physical activity (recreational/occupational/sedentary behavior) and histologically confirmed ovarian cancer. Meta-analysis was restricted to the subset of these studies that reported on recreational physical activity. In our case-control study, we observed weakly inverse or null associations between recreational physical activity and risk of epithelial ovarian cancer overall. There was no evidence that the effects varied by tumor behavior or histologic subtype. Twelve studies were included in the meta-analysis, which gave summary estimates of 0.79 (95% confidence interval, 0.70-0.85) for case-control studies and 0.81 (95% confidence interval, 0.57-1.17) for cohort studies for the risk of ovarian cancer associated with highest versus lowest levels of recreational physical activity. Thus, pooled results from observational studies suggest that a modest inverse association exists between level of recreational physical activity and

  15. Expression of seprase in effusions from patients with epithelial ovarian carcinoma

    Institute of Scientific and Technical Information of China (English)

    ZHANG Meng-zhen; QIAO Yu-huan; Jahn M Nesland; SUO Zhen-he

    2007-01-01

    Background Seprase plays an important role in malignant cell invasion and metastasis by degrading the extracellular matrix. Hcwever, its clinical significance remains largely unknown. The objective of the current study was to evaluate the expression of seprase in effusions from patients with epithelial ovarian carcinoma and its clinical values.Methods Immunohistochemistry was used to examine the expression of seprase protein in a series of 74 malignant peritoneal (n=64) and pleural (n=10) effusions from Norwegian patients with epithelial ovarian carcinoma. Additionally, 34 effusions were evaluated using the Western blotting. Nine reactive effusions, obtained from patients with benign lesions,served as a control group. Statistical analyses were carried out by Chi-square test and Kaplan-Meier method.Results In the 74 malignant effusion specimens, 57 (77.02%) were positive for seprase, while only 2 (22.22%) of the control group were positively stained (P=0.001). In the malignant effusions, 17 (22.97%), 22 (29.73%), 22 (29.73%), 13 (17.57%) had negative, weak, moderate and strong seprase protein expression, respectively. The expression of seprase protein was predominant in cytoplasm of carcinoma cells. Increased seprase protein was negatively associated with the overall survival rate of the patients (P=0.03). However, there was no significant correlation between protein expression and FIGO stage, age, histology, and histological grade. By Western blotting, 27 of the 34 effusions showed the presence of both 170-kD dimeric form and 97-KD monomeric form of seprase while only 1 of the 34 had 170-KD dimeric form,which was consistent with the results of immunohistochemistry (P=0.05).Conclusions Seprase may be involved in the development of ovarian cancer, and is a potential predictive marker for the disease.

  16. The expression of immunohistochemical markers estrogen receptor, progesterone receptor, Her-2-neu, p53 and Ki-67 in epithelial ovarian tumors and its correlation with clinicopathologic variables

    Directory of Open Access Journals (Sweden)

    Mary T Sylvia

    2012-01-01

    Full Text Available Background: This study aims to evaluate the expression of estrogen receptor alpha (ER α, progesterone receptor A (PRA, Her-2-neu, p53, and Ki-67 in epithelial ovarian tumors and their correlation with various clinicopathologic variables. Materials and Methods: This study included 60 consecutive cases of epithelial ovarian tumors. Sections of 4 μm were taken from paraffin embedded tissue blocks for immunohistochemistry (IHC. Statistical analysis was done using Chi square test, ANOVA. Results: ER α had lower expression in benign (29% and PRA higher expression in malignant (63.6% tumors. ERα, PRA had higher expression in serous (72.72%, 57.14%, postmenopausal (81.8%, 71.42%, advanced stage (63.63%, 52.38%, grade 3 (45.45%, 38.09%, and tumors with ascites (90.90%, 85.7%. Her-2-neu, p53 were negative in benign and higher in malignant (21%, 57.6%, serous (71.42%, 57.89%, grade 3 (57.14%, 31.57%, and tumors with ascites (85.7%, 84.21%. Ki-67 had a significant higher expression in malignant (48.6± 26.76, serous (55.43± 27.85, and grade 3 tumors (68 ± 22. CA-125 levels were significantly higher in malignant, serous, advanced stage, grade 3 and ER α, Her-2-neu and p53 positive tumors. Conclusion: ERα, PRA expression in tumors with adverse prognostic factors support the mitogenic role of estrogen and estrogenic regulation of PR. Her-2-neu and p53 expression only in malignant tumors suggest their carcinogenic role and aid in the differentiation of borderline and malignant tumors. Higher Ki-67 in tumors with adverse prognostic factors would help in prognostication and differentiation. Lack of co-expression of markers proves the extreme heterogeneity of ovarian tumors. These markers may aid in differentiation and prognostication of ovarian tumors.

  17. Epothilones in epithelial ovarian, fallopian tube, or primary peritoneal cancer: a systematic review

    Directory of Open Access Journals (Sweden)

    Zagouri F

    2015-08-01

    Full Text Available Flora Zagouri,1 Theodoros N Sergentanis,2 Dimosthenis Chrysikos,2 Meletios-Athanassios Dimopoulos,1 Aristotle Bamias1 1Department of Clinical Therapeutics, Alexandra Hospital, 2First Propaedeutic Surgical Department, Hippokration Hospital, University of Athens, Athens, Greece Abstract: Ovarian cancer is the most lethal gynecologic malignancy; consequently, there is a need for effective therapies. Epothilones are microtubule-stabilizing agents that inhibit cell growth. Currently, patupilone and its four synthetic derivatives ixabepilone, BMS-310705, sagopilone, 20-desmethyl-20-methylsulfanyl epothilone B and epothilone D, as well as its derivative KOS-1584, are under clinical evaluation. This is the first systematic review conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines that synthesizes all available data emerging from trials and evaluates the efficacy and safety of epothilones in epithelial ovarian, primary fallopian tube, and primary peritoneal cancer. Despite the fact that epothilones have proven active in taxane-resistant settings in preclinical models, it is not yet clear from Phase II/III studies reviewed here that their clinical activity is superior to that of taxanes. Nevertheless, responses to epothilones have been observed in platinum-refractory/resistant ovarian cancer patients. Moreover, despite the shared mechanism of action of epothilones, their clinical profile seems clearly different, with diarrhea being the most common dose-limiting toxicity encountered with patupilone, whereas neutropenia and sensory neuropathy are the most common toxic effects observed with the other epothilones. In any case, randomized trials comparing epothilones with standard treatments seem warranted to define further the role of these agents, whereas biomarker analysis might further optimize patient selection. Keywords: ovarian cancer, epothilone, patupilone, ixabepilone, systematic

  18. Inflammatory markers and risk of epithelial ovarian cancer by tumor subtypes: the EPIC cohort

    Science.gov (United States)

    Ose, Jennifer; Schock, Helena; Tjonneland, Anne; Hansen, Louise; Overvad, Kim; Dossus, Laure; Clavel-Chapelon, Francoise; Baglietto, Laura; Boeing, Heiner; Trichopolou, Antonia; Benetou, Vassiliki; Lagiou, Pagona; Masala, Giovanna; Tagliabue, Giovanna; Tumino, Rosario; Sacerdote, Carlotta; Mattiello, Amalia; de Mesquita, H.Bas Bueno; Peeters, Petra H M; Onland-Moret, N Charlotte; Weiderpass, Elisabete; Gram, Inger T; Sánchez, Soledad; Obon-Santacana, Mireia; Sànchez-Pérez, Maria-José; Larrañaga, Nerea; Castaño, José María Huerta; Ardanaz, Eva; Brändstedt, Jenny; Lundin, Eva; Idahl, Annika; Travis, Ruth C; Khaw, Kay-Tee; Rinaldi, Sabina; Romieu, Isabelle; Merrit, Melissa A; Gunter, Marc J; Riboli, Elio; Kaaks, Rudolf; Fortner, Renée T

    2015-01-01

    Background Evidence suggests an etiologic role for inflammation in ovarian carcinogenesis and heterogeneity between tumor subtypes and anthropometric indices. Prospective studies on circulating inflammatory markers and epithelial invasive ovarian cancer (EOC) have predominantly investigated overall risk; data characterizing risk by tumor characteristics (histology, grade, stage, dualistic model of ovarian carcinogenesis) and anthropometric indices are sparse. Methods We conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to evaluate C-reactive protein (CRP), interleukin-6 (IL-6), and EOC risk by tumor characteristics. A total of 754 eligible EOC cases were identified; two controls (n=1,497) were matched per case. We used multivariable conditional logistic regression to assess associations. Results CRP and IL-6 were not associated with overall EOC risk. However, consistent with prior research, CRP >10 vs. CRP ≤1 mg/L was associated with higher overall EOC risk (OR=1.67 [1.03 - 2.70]). We did not observe significant associations or heterogeneity in analyses by tumor characteristics. In analyses stratified by waist circumference, inflammatory markers were associated with higher risk among women with higher waist circumference; no association was observed for women with normal waist circumference: (e.g., IL-6: waist ≤80: ORlog2=0.97 [0.81 - 1.16]; waist >88: ORlog2=1.78 [1.28 - 2.48], pheterogeneity ≤0.01). Conclusions Our data suggest that high CRP is associated with increased risk of overall EOC, and that IL-6 and CRP may be associated with EOC risk among women with higher adiposity. Impact Our data add to global evidence that ovarian carcinogenesis may be promoted by an inflammatory milieu. PMID:25855626

  19. Specific point mutations in key redox enzymes are associated with chemoresistance in epithelial ovarian cancer.

    Science.gov (United States)

    Fletcher, Nicole M; Belotte, Jimmy; Saed, Mohammed G; Memaj, Ira; Diamond, Michael P; Morris, Robert T; Saed, Ghassan M

    2017-01-01

    Oxidative stress plays an important role in the pathophysiology of ovarian cancer. Resistance to chemotherapy presents a significant challenge for ovarian cancer treatment. Specific single nucleotide polymorphisms (SNPs) in key redox enzymes have been associated with ovarian cancer survival and progression. The objective of this study was to determine whether chemotherapy induces point mutations in key redox enzymes that lead to the acquisition of chemoresistance in epithelial ovarian cancer (EOC). Human EOC cell lines and their chemoresistant counterpart were utilized for this study. Specific SNPs in key redox enzymes were analyzed by TaqMan SNP Genotyping. Activities and levels of key redox enzymes were determined by real-time RT-PCR, ELISA and a greiss assay. Point mutations in key redox enzymes were introduced into sensitive EOC cells via the CRISPR/Cas9 system. Cell viability and IC50 for cisplatin were determined by the MTT Cell Proliferation Assay. Data was analyzed with SPSS using Student's two-tailed t-tests and One-way ANOVA followed by Dunnett's or Tukey's post hoc tests, penhancement in oxidative stress as compared to sensitive counterparts. Additionally, chemoresistant EOC cells manifested specific point mutations, which are associated with altered enzymatic activity, in key redox enzymes that are not detected in sensitive counterparts. Supplementation of an antioxidant was able to successfully sensitize EOC cells to chemotherapeutics. Causality was established by the induction of these point mutations in sensitive EOC cells, which resulted in a significant increase in the level of chemoresistance. These findings indicate that chemotherapy induces specific point mutations in key redox enzymes that contribute to the acquisition of chemoresistance in EOC cells, highlighting a potential novel mechanism. Identification of targets for chemoresistance with either biomarker and/or screening potential will have a significant impact for the treatment of this

  20. Polymorphisms in stromal genes and susceptibility to serous epithelial ovarian cancer: a report from the Ovarian Cancer Association Consortium.

    Directory of Open Access Journals (Sweden)

    Ernest K Amankwah

    Full Text Available Alterations in stromal tissue components can inhibit or promote epithelial tumorigenesis. Decorin (DCN and lumican (LUM show reduced stromal expression in serous epithelial ovarian cancer (sEOC. We hypothesized that common variants in these genes associate with risk. Associations with sEOC among Caucasians were estimated with odds ratios (OR among 397 cases and 920 controls in two U.S.-based studies (discovery set, 436 cases and 1,098 controls in Australia (replication set 1 and a consortium of 15 studies comprising 1,668 cases and 4,249 controls (replication set 2. The discovery set and replication set 1 (833 cases and 2,013 controls showed statistically homogeneous (P(heterogeneity≥0.48 decreased risks of sEOC at four variants: DCN rs3138165, rs13312816 and rs516115, and LUM rs17018765 (OR = 0.6 to 0.9; P(trend = 0.001 to 0.03. Results from replication set 2 were statistically homogeneous (P(heterogeneity≥0.13 and associated with increased risks at DCN rs3138165 and rs13312816, and LUM rs17018765: all ORs = 1.2; P(trend≤0.02. The ORs at the four variants were statistically heterogeneous across all 18 studies (P(heterogeneity≤0.03, which precluded combining. In post-hoc analyses, interactions were observed between each variant and recruitment period (P(interaction≤0.003, age at diagnosis (P(interaction = 0.04, and year of diagnosis (P(interaction = 0.05 in the five studies with available information (1,044 cases, 2,469 controls. We conclude that variants in DCN and LUM are not directly associated with sEOC, and that confirmation of possible effect modification of the variants by non-genetic factors is required.

  1. Ursolic acid inhibits the proliferation of human ovarian cancer stem-like cells through epithelial-mesenchymal transition.

    Science.gov (United States)

    Zhang, Jie; Wang, Wenjing; Qian, Lin; Zhang, Qiuwan; Lai, Dongmei; Qi, Cong

    2015-11-01

    Ovarian cancer is the most frequent cause of cancer-related death among all gynecological cancers. Increasing evidence suggests that human ovarian cancer stem-like cells could be enriched under serum-free culture conditions. In the present study, SKOV3 ovarian epithelial cancer cells were cultured for sphere cells. Ursolic acid (UA) with triterpenoid compounds exist widely in food, medicinal herbs and other plants. Evidence shows that UA has anticancer activities in human ovarian cancer cells, but he role of UA in ovarian cancer stem cells (CSCs) remains unknown. The aim of the present study was to investigate the anticancer effects of UA in combination with cisplatin in ovarian CSCs (in vitro and in vivo), along with the molecular mechanism of action. Treatment with UA at various concentrations was examined in combination with cisplatin in human ovarian CSCs. MTT assay and flow cytometry were used for cell viability and apoptosis analysis, and qRT-PCR for stem cell markers and epithelial-mesenchymal transition (EMT) markers for mRNA expression. Transwell assay was employed to observe the migration and invasion of SKOV3 cells and SKOV3 sphere cells after treatment. Moreover, athymic BALB/c-nu nude mice were injected with SKOV3 sphere cells to obtain a xenograft model for in vivo studies. The results showed that CSCs possessed mesenchymal characteristics and EMT ability, and the growth of SKOV3 and sphere cells was significantly inhibited by UA. Transplanted tumors were significantly reduced after injection of UA and UA plus cisplatin. Furthermore, we found that UA could play a role in enhancing the sensitivity of CSCs to cisplatin resistance. Our findings suggested that UA is involved in EMT mechanism to affect the proliferation and apoptosis of human ovarian cancer stem-like cells and it is a potent anti-ovarian cancer agent.

  2. Bevacizumab combination therapy: a review of its use in patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer.

    Science.gov (United States)

    Dhillon, Sohita

    2013-08-01

    Bevacizumab (Avastin®) is a recombinant, humanized anti-vascular endothelial growth factor (VEGF) monoclonal antibody that neutralizes the biological activity of VEGF and inhibits tumor angiogenesis. In the EU, in adult patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer, bevacizumab (in combination with carboplatin and paclitaxel) is approved for the first-line treatment of advanced disease and (in combination with carboplatin and gemcitabine) is approved for the treatment of patients with first recurrence of platinum-sensitive disease who have not received prior therapy with bevacizumab or other VEGF inhibitors or VEGF receptor-targeted agents. This article summarizes the pharmacology of bevacizumab and reviews the efficacy and tolerability of bevacizumab combination therapy in well-designed clinical studies in these indications. The addition of bevacizumab to first-line carboplatin plus paclitaxel, followed by bevacizumab maintenance therapy significantly prolonged progression-free survival in women with newly-diagnosed advanced disease (GOG-0218 and ICON7 studies). Progression-free survival was also significantly prolonged after second-line treatment with bevacizumab in combination with carboplatin and gemcitabine, followed by maintenance treatment with bevacizumab alone in women with recurrence (≥ 6 months after front-line platinum-based therapy) of platinum-sensitive disease (OCEANS study). Bevacizumab combination therapy had a generally acceptable tolerability profile in these studies, with the nature of adverse events generally similar to that observed in previous clinical trials in patients with other solid tumors. Although several unanswered questions remain, such as the optimal dosage and duration of treatment, current evidence suggests that bevacizumab combination therapy extends the treatment options available for patients with ovarian cancer.

  3. Differential Expression of Claudin Family Proteins in Mouse Ovarian Serous Papillary Epithelial Adenoma in Aging FSH Receptor-Deficient Mutants

    Directory of Open Access Journals (Sweden)

    Jayaprakash Aravindakshan

    2006-12-01

    Full Text Available Ovarian cancer is a deadly disease with long latency. To understand the consequences of loss of folliclestimulating hormone receptor (FSH-R signaling and to explore why the atrophic and anovulatory ovaries of follitropin receptor knockout (FORKO mice develop different types of ovarian tumors, including serous papillary epithelial adenoma later in life, we used mRNA expression profiling to gain a comprehensive view of misregulated genes. Using real-time quantitative reverse transcription-polymerase chain reaction, protein analysis, and cellular localization, we show, for the first time, in vivo evidence that, in the absence of FSH-R signaling, claudin-3, claudin-4, and claudin-11 are selectively upregulated, whereas claudin-1 decreases in ovarian surface epithelium and tumors in comparison to wild type. In vitro experiments using a mouse ovarian surface epithelial cell line derived from wild-type females reveal direct hormonal influence on claudin proteins. Although recent studies suggest that cell junction proteins are differentially expressed in ovarian tumors in women, the etiology of such changes remains unclear. Our results suggest an altered hormonal environment resulting from FSH-R loss as a cause of early changes in tight junction proteins that predispose the ovary to late-onset tumors that occur with aging. More importantly, this study identifies claudin-11 overexpression in mouse ovarian serous cystadenoma.

  4. Common variants at the CHEK2 gene locus and risk of epithelial ovarian cancer

    DEFF Research Database (Denmark)

    Lawrenson, Kate; Iversen, Edwin S; Tyrer, Jonathan

    2015-01-01

    Genome-wide association studies have identified 20 genomic regions associated with risk of epithelial ovarian cancer (EOC), but many additional risk variants may exist. Here, we evaluated associations between common genetic variants [single nucleotide polymorphisms (SNPs) and indels] in DNA repai...

  5. Genome-wide association study of subtype-specific epithelial ovarian cancer risk alleles using pooled DNA

    DEFF Research Database (Denmark)

    Earp, Madalene A; Kelemen, Linda E; Magliocco, Anthony M

    2014-01-01

    Epithelial ovarian cancer (EOC) is a heterogeneous cancer with both genetic and environmental risk factors. Variants influencing the risk of developing the less-common EOC subtypes have not been fully investigated. We performed a genome-wide association study (GWAS) of EOC according to subtype by...

  6. Germline polymorphisms in an enhancer of PSIP1 are associated with progression-free survival in epithelial ovarian cancer

    DEFF Research Database (Denmark)

    French, Juliet D; Johnatty, Sharon E; Lu, Yi

    2016-01-01

    Women with epithelial ovarian cancer (EOC) are usually treated with platinum/taxane therapy after cytoreductive surgery but there is considerable inter-individual variation in response. To identify germline single-nucleotide polymorphisms (SNPs) that contribute to variations in individual respons...

  7. Functional polymorphisms in the TERT promoter are associated with risk of serous epithelial ovarian and breast cancers

    NARCIS (Netherlands)

    Beesley, J.; Pickett, H.A.; Johnatty, S.E.; Dunning, A.M.; Chen, X.; Li, J.; Michailidou, K.; Lu, Y.; Rider, D.N.; Palmieri, R.T.; Stutz, M.D.; Lambrechts, D.; Despierre, E.; Lambrechts, S.; Vergote, I.; Chang-Claude, J.; Nickels, S.; Vrieling, A.; Flesch-Janys, D.; Wang-Gohrke, S.; Eilber, U.; Bogdanova, N.; Antonenkova, N.; Runnebaum, I.B.; Dork, T.; Goodman, M.T.; Lurie, G.; Wilkens, L.R.; Matsuno, R.K.; Kiemeney, L.A.L.M.; Aben, K.K.H.; Marees, T.; Massuger, L.F.A.G.; Fridley, B.L.; Vierkant, R.A.; Bandera, E.V.; Olson, S.H.; Orlow, I.; Rodriguez-Rodriguez, L.; Cook, L.S.; Le, N.D.; Brooks-Wilson, A.; Kelemen, L.E.; Campbell, I.; Gayther, S.A.; Ramus, S.J.; Gentry-Maharaj, A.; Menon, U.; Ahmed, S.; Baynes, C.; Pharoah, P.D.; Muir, K.; Lophatananon, A.; Chaiwerawattana, A.; Wiangnon, S.; MacGregor, S.; Easton, D.F.; Reddel, R.R.; Goode, E.L.; Chenevix-Trench, G.

    2011-01-01

    Genetic variation at the TERT-CLPTM1L locus at 5p15.33 is associated with susceptibility to several cancers, including epithelial ovarian cancer (EOC). We have carried out fine-mapping of this region in EOC which implicates an association with a single nucleotide polymorphism (SNP) within the TERT p

  8. Association between BRCA1 and BRCA2 mutations and survival in women with invasive epithelial ovarian cancer

    DEFF Research Database (Denmark)

    Bolton, Kelly L; Chenevix-Trench, Georgia; Goh, Cindy;

    2012-01-01

    Approximately 10% of women with invasive epithelial ovarian cancer (EOC) carry deleterious germline mutations in BRCA1 or BRCA2. A recent article suggested that BRCA2-related EOC was associated with an improved prognosis, but the effect of BRCA1 remains unclear....

  9. Potential Application of Curcumin and Its Analogues in the Treatment Strategy of Patients with Primary Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Katarzyna M. Terlikowska

    2014-11-01

    Full Text Available Recent findings on the molecular basis of ovarian cancer development and progression create new opportunities to develop anticancer medications that would affect specific metabolic pathways and decrease side systemic toxicity of conventional treatment. Among new possibilities for cancer chemoprevention, much attention is paid to curcumin—A broad-spectrum anticancer polyphenolic derivative extracted from the rhizome of Curcuma longa L. According to ClinicalTrials.gov at present there are no running pilot studies, which could assess possible therapeutic benefits from curcumin supplementation to patients with primary epithelial ovarian cancer. Therefore, the goal of this review was to evaluate potential preclinical properties of curcumin and its new analogues on the basis of in vivo and in vitro ovarian cancer studies. Curcumin and its different formulations have been shown to display multifunctional mechanisms of anticancer activity, not only in platinum-resistant primary epithelial ovarian cancer, but also in multidrug resistant cancer cells/xenografts models. Curcumin administered together with platinum-taxane chemotherapeutics have been reported to demonstrate synergistic effects, sensitize resistant cells to drugs, and decrease their biologically effective doses. An accumulating body of evidence suggests that curcumin, due to its long-term safety and an excellent profile of side effects should be considered as a beneficial support in ovarian cancer treatment strategies, especially in patients with platinum-resistant primary epithelial recurrent ovarian cancer or multidrug resistant disease. Although the prospect of curcumin and its formulations as anticancer agents in ovarian cancer treatment strategy appears to be challenging, and at the same time promising, there is a further need to evaluate its effectiveness in clinical studies.

  10. Discovery of dachshund 2 protein as a novel biomarker of poor prognosis in epithelial ovarian cancer

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    Nodin Björn

    2012-01-01

    Full Text Available Abstract Background The Dachshund homolog 2 (DACH2 gene has been implicated in development of the female genital tract in mouse models and premature ovarian failure syndrome, but to date, its expression in human normal and cancerous tissue remains unexplored. Using the Human Protein Atlas as a tool for cancer biomarker discovery, DACH2 protein was found to be differentially expressed in epithelial ovarian cancer (EOC. Here, the expression and prognostic significance of DACH2 was further evaluated in ovarian cancer cell lines and human EOC samples. Methods Immunohistochemical expression of DACH2 was examined in tissue microarrays with 143 incident EOC cases from two prospective, population-based cohorts, including a subset of benign-appearing fallopian tubes (n = 32. A nuclear score (NS, i.e. multiplier of staining fraction and intensity, was calculated. For survival analyses, cases were dichotomized into low (NS 3 using classification and regression tree analysis. Kaplan Meier analysis and Cox proportional hazards modelling were used to assess the impact of DACH2 expression on survival. DACH2 expression was analysed in the cisplatin sensitive ovarian cancer cell line A2780 and its cisplatin resistant derivative A2780-Cp70. The specificity of the DACH2 antibody was tested using siRNA-mediated silencing of DACH2 in A2780-Cp70 cells. Results DACH2 expression was considerably higher in the cisplatin resistant A2780-Cp70 cells compared to the cisplatin-sensitive A2780 cells. While present in all sampled fallopian tubes, DACH2 expression ranged from negative to strong in EOC. In EOC, DACH2 expression correlated with several proteins involved in DNA integrity and repair, and proliferation. DACH2 expression was significantly higher in carcinoma of the serous subtype compared to non-serous carcinoma. In the full cohort, high DACH2 expression was significantly associated with poor prognosis in univariable analysis, and in carcinoma of the serous subtype

  11. Deregulation of let-7e in epithelial ovarian cancer promotes the development of resistance to cisplatin

    Science.gov (United States)

    Cai, J; Yang, C; Yang, Q; Ding, H; Jia, J; Guo, J; Wang, J; Wang, Z

    2013-01-01

    Drug resistance remains a major clinical obstacle to successful treatment in ovarian cancer patients, and the evidence of microRNAs involvement in drug resistance has been emerging recently. In this report, we investigated the role of let-7e in the development of cisplatin-resistant ovarian cancer. On the cellular level, let-7e expression was significantly reduced in cisplatin-resistant human epithelial ovarian cancer (EOC) cell line A2780/CP compared with parental A2780 cell and decreased in a concentration-dependent manner in A2780, SKOV3 and ES2 cells treated with cisplatin. Overexpression of let-7e by transfection of agomir could resensitize A2780/CP and reduce the expression of cisplatin-resistant-related proteins enhancer of zeste 2 (EZH2) and cyclin D1 (CCND1), whereas let-7e inhibitors increased resistance to cisplatin in parental A2780 cells. Quantitative methylation-specific PCR analysis showed hypermethylation of the CpG island adjacent to let-7e in A2780/CP cells, and demethylation treatment with 5-aza-CdR or transfection of pYr-let-7e-shRNA plasmid containing unmethylated let-7e DNA sequence could restore let-7e expression and partly reduce the chemoresistance. In addition, cisplatin combined with let-7e agomirs inhibited the growth of A2780/CP xenograft more effectively than cisplatin alone. Diminished expression of EZH2 and CCND1 and higher cisplatin concentrations in tumor tissue of mice subjected to administration of let-7e agomirs in addition to cisplatin were revealed by immunohistochemistry and atomic absorption spectroscopy, respectively. Taken together, our findings suggest that let-7e may act as a promising therapeutic target for improvement of the sensibility to cisplatin in EOC. PMID:24100610

  12. Characterization of DOK1, a candidate tumor suppressor gene, in epithelial ovarian cancer.

    Science.gov (United States)

    Mercier, Pierre-Luc; Bachvarova, Magdalena; Plante, Marie; Gregoire, Jean; Renaud, Marie-Claude; Ghani, Karim; Têtu, Bernard; Bairati, Isabelle; Bachvarov, Dimcho

    2011-10-01

    In attempt to discover novel aberrantly hypermethylated genes with putative tumor suppressor function in epithelial ovarian cancer (EOC), we applied expression profiling following pharmacologic inhibition of DNA methylation in EOC cell lines. Among the genes identified, one of particular interest was DOK1, or downstream of tyrosine kinase 1, previously recognized as a candidate tumor suppressor gene (TSG) for leukemia and other human malignancies. Using bisulfite sequencing, we determined that a 5'-non-coding DNA region (located at nt -1158 to -850, upstream of the DOK1 translation start codon) was extensively hypermethylated in primary serous EOC tumors compared with normal ovarian specimens; however, this hypermethylation was not associated with DOK1 suppression. On the contrary, DOK1 was found to be strongly overexpressed in serous EOC tumors as compared to normal tissue and importantly, DOK1 overexpression significantly correlated with improved progression-free survival (PFS) values of serous EOC patients. Ectopic modulation of DOK1 expression in EOC cells and consecutive functional analyses pointed toward association of DOK1 expression with increased EOC cell migration and proliferation, and better sensitivity to cisplatin treatment. Gene expression profiling and consecutive network and pathway analyses were also confirmative for DOK1 association with EOC cell migration and proliferation. These analyses were also indicative for DOK1 protective role in EOC tumorigenesis, linked to DOK1-mediated induction of some tumor suppressor factors and its suppression of pro-metastasis genes. Taken together, our findings are suggestive for a possible tumor suppressor role of DOK1 in EOC; however its implication in enhanced EOC cell migration and proliferation restrain us to conclude that DOK1 represents a true TSG in EOC. Further studies are needed to more completely elucidate the functional implications of DOK1 and other members of the DOK gene family in ovarian

  13. CIAPIN1 nuclear accumulation predicts poor clinical outcome in epithelial ovarian cancer

    Directory of Open Access Journals (Sweden)

    Cai Xiaolan

    2012-06-01

    Full Text Available Abstract Background Epithelial ovarian cancer (EOC is an aggressive disease with poor prognosis. The expression of cytokine-induced apoptosis inhibitor 1 (CIAPIN1 correlates with the malignant progression of several cancers. However, the relationship between the subcellular localization of CIAPIN1 and clinical characteristics in EOC remains unclear. Methods Immunohistochemistry was performed to detect CIAPIN1 expression in 108 EOC tissues. CIAPIN1 expressions in eight fresh EOC tissues were detected by Western blotting. The relationship between CIAPIN1 subcellular expression and patients’ clinicopathological features, including prognosis, was evaluated. Immunohistochemistry and immunofluorescence were employed to assess the CIAPIN1 subcellular localization in the EOC cell lines A2780 and HO8910. In addition, all patients were followed up to assess the prognostic value of CIAPIN1 in patients with EOC. Results CIAPIN1 is highly expressed in EOC, but is present at low levels in paired non-cancerous ovarian epithelial tissues. The results of Western blotting were in accordance with the immunohistochemical results. Poor differentiation of the tumors and EOC cell lines correlated with higher levels of CIAPIN1 nuclear expression. CIAPIN1 nuclear expression significantly correlated with the Federation International of Gynecology and Obstetrics (FIGO stage and histological differentiation (P = 0.034 and P P  Conclusions CIAPIN1 might play a crucial role in the differentiation of EOC cells. Elevated expression of nuclear CIAPIN1 negatively correlated with the survival of EOC patients, suggesting that nuclear CIAPIN1 might serve as a prognostic biomarker for EOC patients.

  14. CAP1 is overexpressed in human epithelial ovarian cancer and promotes cell proliferation.

    Science.gov (United States)

    Hua, Minhui; Yan, Sujuan; Deng, Yan; Xi, Qinghua; Liu, Rong; Yang, Shuyun; Liu, Jian; Tang, Chunhui; Wang, Yingying; Zhong, Jianxin

    2015-04-01

    Adenylate cyclase-associated protein 1 (CAP1) regulates both actin filaments and the Ras/cAMP pathway in yeast, and has been found play a role in cell motility and in the development of certain types of cancer. In the present study, we investigated CAP1 gene expression in human epithelial ovarian cancer (EOC). Western blot analysis and immunohistochemistry were performed using EOC tissue samples and the results revealed that CAP1 expression increased with the increasing grade of EOC. In the normal ovarian tissue samples however, CAP1 expression was barely detected. Using Pearson's χ2 test, it was demonstrated that CAP1 expression was associated with the histological grade and Ki-67 expression. Kaplan-Meier analysis revealed that a higher CAP1 expression in patients with EOC was associated with a poorer prognosis. In in vitro experiments using HO-8910 EOC cells, the expression of CAP1 was knocked down using siRNA. The proliferation of the HO-8910 cells was then determined by cell cycle analysis and cell proliferation assay using the cell counting kit-8 and flow cytometry. The results revealed that the loss of CAP1 expression inhibited cell cycle progression. These findings suggest that a high expression of CAP1 is involved in the pathogenesis of EOC, and that the downregulation of CAP1 in tumor cells may be a therapeutic target for the treatment of patients with EOC.

  15. Identification of six new susceptibility loci for invasive epithelial ovarian cancer.

    Science.gov (United States)

    Kuchenbaecker, Karoline B; Ramus, Susan J; Tyrer, Jonathan; Lee, Andrew; Shen, Howard C; Beesley, Jonathan; Lawrenson, Kate; McGuffog, Lesley; Healey, Sue; Lee, Janet M; Spindler, Tassja J; Lin, Yvonne G; Pejovic, Tanja; Bean, Yukie; Li, Qiyuan; Coetzee, Simon; Hazelett, Dennis; Miron, Alexander; Southey, Melissa; Terry, Mary Beth; Goldgar, David E; Buys, Saundra S; Janavicius, Ramunas; Dorfling, Cecilia M; van Rensburg, Elizabeth J; Neuhausen, Susan L; Ding, Yuan Chun; Hansen, Thomas V O; Jønson, Lars; Gerdes, Anne-Marie; Ejlertsen, Bent; Barrowdale, Daniel; Dennis, Joe; Benitez, Javier; Osorio, Ana; Garcia, Maria Jose; Komenaka, Ian; Weitzel, Jeffrey N; Ganschow, Pamela; Peterlongo, Paolo; Bernard, Loris; Viel, Alessandra; Bonanni, Bernardo; Peissel, Bernard; Manoukian, Siranoush; Radice, Paolo; Papi, Laura; Ottini, Laura; Fostira, Florentia; Konstantopoulou, Irene; Garber, Judy; Frost, Debra; Perkins, Jo; Platte, Radka; Ellis, Steve; Godwin, Andrew K; Schmutzler, Rita Katharina; Meindl, Alfons; Engel, Christoph; Sutter, Christian; Sinilnikova, Olga M; Damiola, Francesca; Mazoyer, Sylvie; Stoppa-Lyonnet, Dominique; Claes, Kathleen; De Leeneer, Kim; Kirk, Judy; Rodriguez, Gustavo C; Piedmonte, Marion; O'Malley, David M; de la Hoya, Miguel; Caldes, Trinidad; Aittomäki, Kristiina; Nevanlinna, Heli; Collée, J Margriet; Rookus, Matti A; Oosterwijk, Jan C; Tihomirova, Laima; Tung, Nadine; Hamann, Ute; Isaccs, Claudine; Tischkowitz, Marc; Imyanitov, Evgeny N; Caligo, Maria A; Campbell, Ian G; Hogervorst, Frans B L; Olah, Edith; Diez, Orland; Blanco, Ignacio; Brunet, Joan; Lazaro, Conxi; Pujana, Miquel Angel; Jakubowska, Anna; Gronwald, Jacek; Lubinski, Jan; Sukiennicki, Grzegorz; Barkardottir, Rosa B; Plante, Marie; Simard, Jacques; Soucy, Penny; Montagna, Marco; Tognazzo, Silvia; Teixeira, Manuel R; Pankratz, Vernon S; Wang, Xianshu; Lindor, Noralane; Szabo, Csilla I; Kauff, Noah; Vijai, Joseph; Aghajanian, Carol A; Pfeiler, Georg; Berger, Andreas; Singer, Christian F; Tea, Muy-Kheng; Phelan, Catherine M; Greene, Mark H; Mai, Phuong L; Rennert, Gad; Mulligan, Anna Marie; Tchatchou, Sandrine; Andrulis, Irene L; Glendon, Gord; Toland, Amanda Ewart; Jensen, Uffe Birk; Kruse, Torben A; Thomassen, Mads; Bojesen, Anders; Zidan, Jamal; Friedman, Eitan; Laitman, Yael; Soller, Maria; Liljegren, Annelie; Arver, Brita; Einbeigi, Zakaria; Stenmark-Askmalm, Marie; Olopade, Olufunmilayo I; Nussbaum, Robert L; Rebbeck, Timothy R; Nathanson, Katherine L; Domchek, Susan M; Lu, Karen H; Karlan, Beth Y; Walsh, Christine; Lester, Jenny; Hein, Alexander; Ekici, Arif B; Beckmann, Matthias W; Fasching, Peter A; Lambrechts, Diether; Van Nieuwenhuysen, Els; Vergote, Ignace; Lambrechts, Sandrina; Dicks, Ed; Doherty, Jennifer A; Wicklund, Kristine G; Rossing, Mary Anne; Rudolph, Anja; Chang-Claude, Jenny; Wang-Gohrke, Shan; Eilber, Ursula; Moysich, Kirsten B; Odunsi, Kunle; Sucheston, Lara; Lele, Shashi; Wilkens, Lynne R; Goodman, Marc T; Thompson, Pamela J; Shvetsov, Yurii B; Runnebaum, Ingo B; Dürst, Matthias; Hillemanns, Peter; Dörk, Thilo; Antonenkova, Natalia; Bogdanova, Natalia; Leminen, Arto; Pelttari, Liisa M; Butzow, Ralf; Modugno, Francesmary; Kelley, Joseph L; Edwards, Robert P; Ness, Roberta B; du Bois, Andreas; Heitz, Florian; Schwaab, Ira; Harter, Philipp; Matsuo, Keitaro; Hosono, Satoyo; Orsulic, Sandra; Jensen, Allan; Kjaer, Susanne Kruger; Hogdall, Estrid; Hasmad, Hanis Nazihah; Azmi, Mat Adenan Noor; Teo, Soo-Hwang; Woo, Yin-Ling; Fridley, Brooke L; Goode, Ellen L; Cunningham, Julie M; Vierkant, Robert A; Bruinsma, Fiona; Giles, Graham G; Liang, Dong; Hildebrandt, Michelle A T; Wu, Xifeng; Levine, Douglas A; Bisogna, Maria; Berchuck, Andrew; Iversen, Edwin S; Schildkraut, Joellen M; Concannon, Patrick; Weber, Rachel Palmieri; Cramer, Daniel W; Terry, Kathryn L; Poole, Elizabeth M; Tworoger, Shelley S; Bandera, Elisa V; Orlow, Irene; Olson, Sara H; Krakstad, Camilla; Salvesen, Helga B; Tangen, Ingvild L; Bjorge, Line; van Altena, Anne M; Aben, Katja K H; Kiemeney, Lambertus A; Massuger, Leon F A G; Kellar, Melissa; Brooks-Wilson, Angela; Kelemen, Linda E; Cook, Linda S; Le, Nhu D; Cybulski, Cezary; Yang, Hannah; Lissowska, Jolanta; Brinton, Louise A; Wentzensen, Nicolas; Hogdall, Claus; Lundvall, Lene; Nedergaard, Lotte; Baker, Helen; Song, Honglin; Eccles, Diana; McNeish, Ian; Paul, James; Carty, Karen; Siddiqui, Nadeem; Glasspool, Rosalind; Whittemore, Alice S; Rothstein, Joseph H; McGuire, Valerie; Sieh, Weiva; Ji, Bu-Tian; Zheng, Wei; Shu, Xiao-Ou; Gao, Yu-Tang; Rosen, Barry; Risch, Harvey A; McLaughlin, John R; Narod, Steven A; Monteiro, Alvaro N; Chen, Ann; Lin, Hui-Yi; Permuth-Wey, Jenny; Sellers, Thomas A; Tsai, Ya-Yu; Chen, Zhihua; Ziogas, Argyrios; Anton-Culver, Hoda; Gentry-Maharaj, Aleksandra; Menon, Usha; Harrington, Patricia; Lee, Alice W; Wu, Anna H; Pearce, Celeste L; Coetzee, Gerry; Pike, Malcolm C; Dansonka-Mieszkowska, Agnieszka; Timorek, Agnieszka; Rzepecka, Iwona K; Kupryjanczyk, Jolanta; Freedman, Matt; Noushmehr, Houtan; Easton, Douglas F; Offit, Kenneth; Couch, Fergus J; Gayther, Simon; Pharoah, Paul P; Antoniou, Antonis C; Chenevix-Trench, Georgia

    2015-02-01

    Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed associations of 11 million genetic variants with EOC risk from 15,437 cases unselected for family history and 30,845 controls and from 15,252 BRCA1 mutation carriers and 8,211 BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results in a meta-analysis. This new study design yielded increased statistical power, leading to the discovery of six new EOC susceptibility loci. Variants at 1p36 (nearest gene, WNT4), 4q26 (SYNPO2), 9q34.2 (ABO) and 17q11.2 (ATAD5) were associated with EOC risk, and at 1p34.3 (RSPO1) and 6p22.1 (GPX6) variants were specifically associated with the serous EOC subtype, all with P < 5 × 10(-8). Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers.

  16. Potential Target Antigens for a Universal Vaccine in Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Renee Vermeij

    2010-01-01

    Full Text Available The prognosis of epithelial ovarian cancer (EOC, the primary cause of death from gynaecological malignancies, has only modestly improved over the last decades. Immunotherapeutic treatment using a cocktail of antigens has been proposed as a “universal” vaccine strategy. We determined the expression of tumor antigens in the context of MHC class I expression in 270 primary tumor samples using tissue microarray. Expression of tumor antigens p53, SP17, survivin, WT1, and NY-ESO-1 was observed in 120 (48.0%, 173 (68.9%, 208 (90.0%, 129 (56.3%, and 27 (11.0% of 270 tumor specimens, respectively. In 93.2% of EOC, at least one of the investigated tumor antigens was (overexpressed. Expression of MHC class I was observed in 78.1% of EOC. In 3 out 4 primary tumors, (overexpression of a tumor antigen combined with MHC class I was observed. These results indicate that a multiepitope vaccine, comprising these antigens, could serve as a universal therapeutic vaccine for the vast majority of ovarian cancer patients.

  17. Clinical outcomes of fertility-sparing treatments in young patients with epithelial ovarian carcinoma

    Institute of Scientific and Technical Information of China (English)

    Jun HU; Li-rong ZHU; Zhi-qing LIANG; Yuan-guang MENG; Hong-yan GUO; Peng-peng QU; Cai-ling MA; Cong-jian XU; Bi-bo YUAN

    2011-01-01

    Objective:To assess the clinical outcomes of fertility-sparing treatments in young patients with epithelial ovarian carcinoma (EOC).Methods:A retrospective study of young EOC inpatients (≤40 years old) was performed during January 1994 and December 2010 in eight institutions.Results:Data were analyzed from 94 patients treated with fertility-sparing surgery with a median follow-up time of 58.7 months.As histologic grade increased,overall survival (OS) and disease-free survival (DFS) of patients receiving fertility-sparing surgery declined.Neither staging surgery nor laparoscopy of early stage EOC with conservative surgery had a significant effect on OS or DFS.Normal menstruation recommenced after chemotherapy in 89% of the fertility-sparing group.Seventeen pregnancies among twelve patients were achieved by the end of the follow-ups.Conclusions:Fertility-sparing treatment for patients with EOC Stage Ⅰ Grade 1 could be cautiously considered for young patients.The surgical procedure and surgical route might not significantly influence the prognosis.Standard chemotherapy is not likely to have an evident impact on ovarian function or fertility in young patients.

  18. Crk-like adapter protein regulates CCL19/CCR7-mediated epithelial-to-mesenchymal transition via ERK signaling pathway in epithelial ovarian carcinomas.

    Science.gov (United States)

    Cheng, Shaomei; Guo, Jingyan; Yang, Qing; Yang, Xiangshan

    2015-03-01

    Recent studies have suggested that Crk-like adapter protein (CrkL) and epithelial-to-mesenchymal transition (EMT) induced by CCL19/CCR7 play an important role in ovarian epithelial carcinogenesis. However, the regulatory mechanisms of CrkL on the CCL19/CCR7 signaling pathways in epithelial ovarian carcinomas (EOC) are not well characterized. Here, CCR7 and CrkL proteins were tested in 30 EOC tissues and cell lines. In vitro, the roles of CrkL in CCL19-stimulated SKOV-3 cell invasion and migration were investigated. In this work, CCR7 and CrkL over-expressed in EOC tissues and cell lines and correlated with FIGO stage and lymph node metastasis. Moreover, CCR7 and CrkL serve as an independent prognostic factor. In SKOV-3 cells, CrkL knockdown markedly suppressed the CCL19-stimulated expression of p-ERK and EMT biomarkers (N-cadherin, Snail and MMP9), compared with control. In contrast, p-AKT expression level did not change. On the other hand, functional analysis revealed CrkL knockdown could significantly decrease SKOV-3 cell invasion number of transwell invasion assay, and wound closure area of wound healing assay, compared to control. In conclusion, CrkL regulates CCL19/CCR7-induced EMT via ERK signaling pathway in EOC patients, which further suggested CrkL could be suggested as an efficient target in ovarian cancer treatment.

  19. Notch and TGFβ form a positive regulatory loop and regulate EMT in epithelial ovarian cancer cells.

    Science.gov (United States)

    Zhou, Jiesi; Jain, Saket; Azad, Abul K; Xu, Xia; Yu, Hai Chuan; Xu, Zhihua; Godbout, Roseline; Fu, YangXin

    2016-08-01

    Epithelial-mesenchymal transition (EMT) plays a critical role in the progression of epithelial ovarian cancer (EOC). However, the mechanisms that regulate EMT in EOC are not fully understood. Here, we report that activation of Notch1 induces EMT in EOC cells as evidenced by downregulation of E-cadherin and cytokeratins, upregulation of Slug and Snail, as well as morphological changes. Interestingly, activation of Notch1 increases TGFβ/Smad signaling by upregulating the expression of TGFβ and TGFβ type 1 receptor. Time course experiments demonstrate that inhibition of Notch by DAPT (a γ-secretase inhibitor) decreases TGFβ-induced phosphorylation of receptor Smads at late, but not at early, timepoints. These results suggest that Notch activation plays a role in sustaining TGFβ/Smad signaling in EOC cells. Furthermore, inhibition of Notch by DAPT decreases TGFβ induction of Slug and repression of E-cadherin and knockdown of Notch1 decreases TGFβ-induced repression of E-cadherin, indicating that Notch is required, at least in part, for TGFβ-induced EMT in EOC cells. On the other hand, TGFβ treatment increases the expression of Notch ligand Jagged1 and Notch target gene HES1 in EOC cells. Functionally, the combination of Notch1 activation and TGFβ treatment is more potent in promoting motility and migration of EOC cells than either stimulation alone. Taken together, our results indicate that Notch and TGFβ form a reciprocal positive regulatory loop and cooperatively regulate EMT and promote EOC cell motility and migration.

  20. Candidate Tumor-Suppressor Gene DLEC1 Is Frequently Downregulated by Promoter Hypermethylation and Histone Hypoacetylation in Human Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Joseph Kwong

    2006-04-01

    Full Text Available Suppression of ovarian tumor growth by chromosome 3p was demonstrated in a previous study. Deleted in Lung and Esophageal Cancer 1 (DLEC1 on 3p22.3 is a candidate tumor suppressor in lung, esophageal, and renal cancers. The potential involvement of DLEC1 in epithelial ovarian cancer remains unknown. In the present study, DLEC1 downregulation was found in ovarian cancer cell lines and primary ovarian tumors. Focus-expressed DLEC1 in two ovarian cancer cell lines resulted in 41% to 52% inhibition of colony formation. No chromosomal loss of chromosome 3p22.3 in any ovarian cancer cell line or tissue was found. Promoter hypermethylation of DLEC1 was detected in ovarian cancer cell lines with reduced DLEC1 transcripts, whereas methylation was not detected in normal ovarian epithelium and DLEC1-expressing ovarian cancer cell lines. Treatment with demethylating agent enhanced DLEC1 expression in 90% (9 of 10 of ovarian cancer cell lines. DLEC1 promoter methylation was examined in 13 high-grade ovarian tumor tissues with DLEC1 downregulation, in which 54% of the tumors showed DLEC1 methylation. In addition, 80% of ovarian cancer cell lines significantly upregulated DLEC1 transcripts after histone deacetylase inhibitor treatment. Therefore, our results suggested that DLEC1 suppressed the growth of ovarian cancer cells and that its downregulation was closely associated with promoter hypermethylation and histone hypoacetylation.

  1. 卵巢上皮性肿瘤中PIEN和Survivin的表达及意义%Expression and significance of SUrvivin and PIEN in epithelial ovarian tumors

    Institute of Scientific and Technical Information of China (English)

    丁月红

    2011-01-01

    Objective To investigate the expression and significance of Survivin and PIEN in epithelial ovarian tumors.Methods Immunohistochemical detection of PTEN and Survivin in 52 cases of epithelial ovarian cancer, 20 cases of benign ovarian epithelial tumors and 18 normal ovarian tissue in rats.Results In normal ovarian tissues Survivin protein expression in non- benign epithelial ovarian tumors and epithelial ovarian cancer in the Survivin protein expression rates were 26.32% ( 5/19 ), 66.67% (30/45), epithelial ovarian cancer in the Survivin protein expression was significantly higher than that of normal ovarian and benign epithelial ovarian tumor group, the difference was significant ( P < 0.05 ); PTEN protein in normal ovarian tissue, benign epithelial ovarian tumors and epithelial ovarian carcinoma were 100.0% (18/18), 95.0% (20/19), 38.5% (20/52).PTEN protein in normal ovarian tissues and benign epithelial ovarian expression of swelling was higher than that of epithelial ovarian cancer (all P < 0.01 ).Conclusions PTEN expression was decreased and increased expression of Survivin and related to the occurrence of epithelial ovarian cancer, the detection of ovarian cancer patients Survivin and PIEN expression for the evaluation of malignancy, and prognosis has important clinical value.%目的 探讨卵巢上皮性肿瘤中PIEN和Survivin的表达及意义.方法 采用免疫组织化学法检测PTEN和survivin在52例卵巢上皮性癌、20例卵巢良性上皮性肿瘤和18例正常卵巢组织标本中的表达.结果 正常卵巢组织中无Survivin蛋白表达,良性上皮性卵巢肿瘤和卵巢上皮性癌中Survivin蛋白表达率分别为26.32%(5/19)、66.67%(30/45),卵巢上皮性癌中Survivin蛋白阳性表达率明显高于正常卵巢及良性上皮性卵巢肿瘤组,差异有显著性(P<0.05);PTEN蛋白在正常卵巢组织、卵巢良性上皮性肿瘤和卵巢上皮性癌中的表达率分别为100.0%(18/18)、95.0%(20/19)、38

  2. mtDNA sequence variants in subtypes of epithelial ovarian cancer stages in relation to ethnic and age difference

    Directory of Open Access Journals (Sweden)

    Yao Xuebiao

    2008-07-01

    Full Text Available Abstract Epithelial ovarian cancer is the fifth leading cause of cancer mortality among women in the United States. For this disease, differences in age-adjusted incidence and survival rates between African American and Caucasian women are substantial. The objective of this study was to examine mtDNA sequence variants in 118 frozen tissues of three subtypes of epithelial ovarian cancer (serous, n = 48 endometrioid, n = 47 and mucinous, n = 23 and matched paracancerous normal tissues (n = 18 in relation to racial/ethnic and age differences. Restriction fragment length polymorphism (RFLP and polymerase chain reaction (PCR-based sequencing were used to evaluate two regions of mtDNA spanning 5317 to 7608 and 8282 to 10110 bp and including ND subunits 2, 3, MT-COI, II, and III, ATPase 8, a part of ATPase 6, and tRNA genes in frozen ovarian tissues obtained from the southern regional Cooperative Human Tissue Network (CHTN and University of Alabama-Birmingham (UAB Ovarian Spore Center. Thirty-nine mtDNA variants were detected of which 28 were previously unreported. One somatic variant of C9500T was observed. A variant, C7028T in the MT-CO1 gene, had an ascending frequency from borderline (8% to stages III/IV (75% among the three ovarian cancer subtypes and stages. It was found in 86% (42/49 of African-American and 43% (37/87 of the Caucasian women. A variant, T8548G in the ATPase 6 gene was detected at a frequency of 72% (18/25 in ovarian serous subtype tissues in stages III/IV. Of the African American patients under age 40, 95% (20/21 harbored the T8548G variant; this was in contrast to only 22% (8/35 of Caucasian patients in same age group. Variants C7256T and G7520A had a frequency of 54% (6/11 in endometrioid stage III; no corresponding variants were observed in mucinous subtype stage III. Furthermore, variants C7256T and G7520A were absent in serous ovarian cancer subtype. Interestingly, the C7520T variant in tRNA gene was present in 74% (36/49 of

  3. Vascular endothelial growth factor polymorphisms and a synchronized examination of plasma and tissue expression in epithelial ovarian cancers.

    Science.gov (United States)

    Bhaskari, J; Premalata, C S; Shilpa, V; Rahul, B; Pallavi, V R; Ramesh, G; Krishnamoorthy, Lakshmi

    2016-01-01

    In this study, we have analyzed six genetic polymorphisms of the VEGF-A gene and correlated the genetic data with plasma and tissue expression of VEGF-A in epithelial ovarian carcinomas. A total of 130 cases including 95 malignant carcinomas, 17 low malignant potential and 18 benign tumours were studied. rs699947, rs833061, rs1570360, rs2010963, rs1413711 and rs3025039 were studied by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Plasma levels of VEGF-A were estimated by enzyme-linked immunosorbent assay (ELISA) and tissue expression of VEGF-A by immunohistochemistry (IHC). Four polymorphisms of the above excluding rs699947 and rs3025039 showed significant association with malignancy, and we observed the presence of positive correlation between haplotype CCGGCC and increased expression of VEGF-A in both plasma and tissues which also correlated with poor prognosis and recurrence suggesting a probable increase in resistance to treatment in such carriers. Highly upregulated tissue expression of VEGF-A was seen in all epithelial ovarian carcinomas with intensity of expression increasing from benign to malignant cases. ELISA data from our study showed an increase in circulating levels of VEGF-A in malignancies. VEGF-A plasma levels can be employed as a biomarker for high-grade malignancy in epithelial ovarian cancers alongside tissue expression and CA-125 levels. This study is unique due to the fact that a simultaneous analysis of plasma and tissue expression has been demonstrated and is a first such study in epithelial ovarian cancers and representing the Indian population (South-east Asian) synchronized with genetic polymorphism data as well.

  4. Desmocollin 3 mediates follicle stimulating hormone-induced ovarian epithelial cancer cell proliferation by activating the EGFR/Akt signaling pathway.

    Science.gov (United States)

    Yang, Xiao; Wang, Jing; Li, Wen-Ping; Jin, Zhi-Jun; Liu, Xiao-Jun

    2015-01-01

    Follicle-stimulating hormone (FSH) is associated with the pathogenesis of ovarian cancer. We sought to explore whether desmocollin 3 (Dsc3) mediates FSH-induced ovarian epithelial cancer cell proliferation and whether the EGFR/Akt signaling pathway may be involved in this process. Dsc3 positivity in ovarian tissue specimens from 72 patients was assessed by immunohistochemistry. The positive expression rates of Dsc3 were similar in ovarian cancer tissues (24/31:77.4%) and borderline ovarian tumor tissues (18/22:81.8%) (P>0.05), but were significantly higher in these cancerous tissues than in benign ovarian cyst tissues (3/19:15.8%) (Pcancer cells (HO8910, Skov3ip, Skov and Hey cells, but not ES-2 and in borderline ovarian MCV152 tumor cells was higher than in the immortalized ovarian epithelial cell line, Moody. FSH up-regulated the expression of Dsc3 and EGFR in a dose- and time-dependent manner. Furthermore, a converse relationship between the expression of Dsc3, EFGR and PI3K/Akt signaling was elucidated using RNA interference and PI3K/Akt inhibitor in the absence and presence of FSH. A role for these proteins in FSH-induced cell proliferation was verified, highlighting their interdependence in mediating ovarian cancer cell function. These results suggest that Dsc3 can mediate FSH-induced ovarian cancer cell proliferation by activating the EGFR/Akt signaling pathway.

  5. Clinical study of Shenqi Fuzheng injection decreasing side-effects of chemotherapy for patients with ovarian epithelial cancer

    Institute of Scientific and Technical Information of China (English)

    Yu Zhang; Jing Wan; Yuebo Yang; Xiaomao Li

    2013-01-01

    Objective:The aim of the study was to observe the clinical ef ects of Shenqi Fuzheng injection decreasing side-ef ects of chemotherapy for patients with ovarian epithelial cancer. Methods:The 36 cases of ovarian epithelial cancer in The Third Af iliated Hospital of SUN Yat-sen University (Guangzhou, China) from June 2010 to June 2013, were randomly divided into the study group and the control group. The study group contained 18 cases using Shenqi Fuzheng injection combined with TP (Taxol+Carboplatin/cisplatin) chemotherapy, and the control group contained 18 cases only using TP chemotherapy without Shenqi Fuzheng injection. During and after chemotherapy, the side-ef ects and therapy ef ects were observed. Re-sults:The grade II of nausea and vomit were less in the study group than that in the control group, which was significantly dif-ferent (P0.05). There was less degree of decrease of lymphocyte in the study group than that in the control group, which was significantly dif erent (P0.05). There was no significant dif erence in chemotherapy ef ect between the two groups (P>0.05). Conclusion:Shenqi Fuzheng injection can in some degree relieve the side ef ects of TP chemotherapy for the patients with ovarian epithelial cancer, including relieving nausea and vomiting, protecting lymphocytes, and has no conflict ef ect on chemotherapy ef icacy.

  6. Prognostic factors in young ovarian cancer patients

    DEFF Research Database (Denmark)

    Klar, M; Hasenburg, A; Hasanov, M;

    2016-01-01

    OBJECTIVES: We evaluated in a large study meta-database of prospectively randomised phase III trials the prognostic factors for progression-free survival (PFS) and overall survival (OS) in patients 40 years of age with advanced epithelial ovarian cancer. METHODS: A total of 5055 patients...... epithelial ovarian cancer, excellent performance status, who had received complete macroscopic upfront cytoreduction and ≥5 chemotherapy cycles. RESULTS: For patients

  7. MicroRNA-183 correlates cancer prognosis, regulates cancer proliferation and bufalin sensitivity in epithelial ovarian caner.

    Science.gov (United States)

    Chen, Huixiao; Zhang, Ling; Zhang, Lili; Du, Jing; Wang, Hongying; Wang, Bin

    2016-01-01

    Background we intended to explore the functional implication of microRNA-183 (miR-183) in predicting clinical prognosis and regulating cancer proliferation and bufalin sensitivity in epithelial ovarian cancer (EOC). Methods In 75 EOC patients, miR-183 expression was examined, by quantitative RT-PCR (qRT-PCR), between paired EOC tumors and adjacent normal tissues, and between tumor samples from patients at early clinical stages and those at advanced clinical stages. The association of serum miR-183 and patients' clinicopathological variables were examined. The overall survival (OS) was estimated by Kaplan-Meier model. And the possibility of miR-183 as a prognostic biomarker for EOC was examined by cox proportional hazard regression model. In EOC cell lines SKOV3 and ES-2 cells, lentiviral transduction was conducted to genetically suppress miR-183. The effect of miR-183 downregulation on EOC in vitro growth, bufalin sensitivity and in vivo tumorigenicity were examined. Results MiR-183 was highly expressed in EOC tumors, as well ass in patients at advanced clinical stages. Serum miR-183 was significantly associated with major clinicopathological variables in EOC patients, such as clinical stage and lymph node metastases. High level of serum miR-183 was associated with poor OS in EOC patients, and proved to be a potential biomarker for EOC. In EOC cell lines, functional assays demonstrated that miR-183 downregulation inhibited cancer proliferation, enhanced bufalin sensitivity and reduced tumorigenicity in vivo. Conclusion MiR-183 may be a prognostic biomarker for EOC, and inhibiting miR-183 may have therapeutic effect to inhibit tumor growth in EOC.

  8. The Thrombospondin-1 Mimetic ABT-510 Increases the Uptake and Effectiveness of Cisplatin and Paclitaxel in a Mouse Model of Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Nicole E. Campbell

    2010-03-01

    Full Text Available Epithelial ovarian cancer (EOC comprises approximately 90% of ovarian cancers and arises from the surface epithelium. Typical treatment of EOC involves cytoreductive surgery combined with chemotherapy. More recent therapies have targeted the tumor vasculature using antiangiogenic compounds such as thrombospondin-1 (TSP-1. TSP-1 mimetic peptides such as ABT-510 have been created and have been in various clinical trials. We have previously shown that ABT-510 reduces abnormal vasculature associated with tumor tissue and increases the presence of mature blood vessels. It has been hypothesized that treatment with antiangiogenic compounds would allow increased delivery of cytotoxic agents and enhance treatment. In this study, we evaluated the potential role of ABT-510 and various chemotherapeutics (cisplatin and paclitaxel on tumor progression, angiogenesis, and the benefits of combinational treatments on tissue uptake and perfusion using an orthotopic syngeneic mouse model of EOC. Animals were treated with ABT-510 (100 mg/kg per day alone or in combination with cisplatin (2 mg/kg per 3 days or paclitaxel (10 mg/kg per 2 days at 60 days after tumor induction. Radiolabeled and fluorescently labeled paclitaxel demonstrated a significant increase in tumor uptake after ABT-510 treatment. Combined treatment with ABT-510 and cisplatin or paclitaxel resulted in a significant increase in tumor cell and tumor endothelial cell apoptosis and a resultant decrease in ovarian tumor size. Combined treatment also regressed secondary lesions and eliminated the presence of abdominal ascites. The results from this study show that through vessel normalization, ABT-510 increases uptake of chemotherapy drugs and can induce regression of advanced ovarian cancer.

  9. The prognostic importance of cyclooxygenase 2 and HER2 expression in epithelial ovarian cancer

    DEFF Research Database (Denmark)

    Dahl Steffensen, Karina; Waldstrøm, M; Jeppesen, U;

    2007-01-01

    Both cyclooxygenase 2 (COX2) and human epidermal growth factor receptor 2 (HER2, also called c-erbB-2) overexpression have been related to a worse prognosis in epithelial ovarian cancer (EOC), but the data are conflicting and the percentage of tumors with overexpression varies widely in different......) and immunohistochemistry (IHC) for evaluation of the HER2 status in EOC. Immunostaining was performed for COX2/HER2 together with FISH analysis for HER2 gene amplification in 160 patients with EOC, FIGO stages IIB-IV. Follow-up was more than 10 years. COX2 overexpression was found in 20.0% of the tumors. With HER2...... staining, 64.4% were scored as 0, 24.4% as 1+, 6.9% as 2+, and 4.4% as 3+. Median survival time for COX2-negative tumors was 21.6 versus 36 months for COX2-positive tumors. The longer survival for COX2 positive was significant by both univariate analysis (P= 0.015) and multivariate analysis (P= 0...

  10. Advances in circulating microRNAs as diagnostic and prognostic markers for ovarian cancer

    Institute of Scientific and Technical Information of China (English)

    Hong Zheng; Jia-Yu Liu; Feng-Ju Song; Ke-Xin Chen

    2013-01-01

    Ovarian cancer is one of the most lethal malignant gynecological tumors. More than 70%of patients with ovarian cancer are diagnosed at advanced stage. The 5-year survival in patients with advanced ovarian cancer is less than 30%because of the lack of effective biomarkers for diagnosis, prognosis, and personalized treatment. MicroRNA (miR) is a class of small noncoding RNAs that negatively regulate gene expression primarily through post-transcriptional repression. Many studies on tissue miR in ovarian cancer have been carried out and show great potential in clinical practice. However, tissue samples are not easily available because sampling causes injury. Researchers have started to focus on plasma/serum miR, assuming that blood samples may replace tissue samples in miR research in the future. Plasma/serum miR research is still in its early stages. Studies on its function in the early diagnosis of ovarian cancer have achieved some progress, but plasma/serum miR profiling for prognosis and personalized treatment of ovarian cancer remains unknown. A thorough understanding of the function of plasma/serum miR in ovarian cancer will facilitate early diagnosis and improve treatment for ovarian cancer.

  11. Chemokine axes CXCL12/CXCR4 and CXCL16/CXCR6 correlate with lymph node metastasis in epithelial ovarian carcinoma

    Institute of Scientific and Technical Information of China (English)

    Li Guo; Zhu-Mei Cui; Jia Zhang; Yu Huang

    2011-01-01

    Recent evidence suggests that the chemokine axis of CXC chemokine ligand-12 and its receptor CXC chemokine receptor-4 (CXCL12/CXCR4) is highly expressed in gynecological tumors and the axis of CXC chemokine ligand-16 and CXC chemokine receptor-6 (CXCL16/CXCR6) is overexpressed in inflammation-associated tumors. This study aimed to determine the relationship between CXCL12/CXCR4, CXCL16/CXCR6 and ovadan carcinoma's clinicopathologic features and prognosis. Accordingly, the expression of these proteins in ovarian tissues was detected by tissue microarray and immunohistochemistry. The expressions of CXCL12/CXCR4 and CXCL16/CXCR6 were significantly higher in epithelial ovadan carcinomas than in normal epithelial ovadan tissues or benign epithelial ovadan tumors. The expression of chemokines CXCL12 and CXCL16 were positively correlated with their receptors CXCR4 and CXCR6 in ovarian carcinoma, respectively (r = 0.300, P < 0.05; r = 0.395, P < 0.05). Moreover, the expression of CXCL12 was related to the occurrence of ascites (X2 = 4.76, P < 0.05), the expression of CXCR4 was significantly related to lymph node metastasis (X2 = 4.37, P < 0.05), the expression of CXCR6 was significantly related to lymph node metastasis (X2 = 7.43, P < 0.05) and histological type (X2 = 33.48, P < 0.05). ln univariate analysis, the expression of CXCR4 and CXCL16 significantly correlated with reduced median survival (X2 = 4.67, P < 0.05; X2 = 4.48, P < 0.05). Therefore, we conclude that the chemokine axes CXCL12/CXCR4 and CXCL16/CXCR6 may play important roles in the growth, proliferation, invasion, and metastasis of epithelial ovarian carcinoma.

  12. Ovarian epithelial cancer: a role for PGE2-synthesis and signalling in malignant transformation and progression

    Directory of Open Access Journals (Sweden)

    Hedin Lars

    2006-11-01

    Full Text Available Abstract Background The involvement of the cyclooxygenases (COX, in particular COX-2, is well documented for many tumours, e.g. colon, breast and prostate cancer, by both experimental and clinical studies. There are epidemiological data from subjects using NSAIDs, and experimental evidence supporting the hypothesis of prostaglandins (PGs as regulators of tumourigenesis in the ovary. One of the end products of PG-synthesis, PGE2, regulates several key-processes, which are characteristic for tumour growth, e.g. angiogenesis, proliferation and apoptosisis. The present study investigated the pathway for PGE2 – synthesis and signalling in ovarian tumourigenesis by analysing specimen from normal ovaries (n = 18, benign (B (n = 8, borderline type (BL (n = 6 and malignant tumours (AC (n = 22. The expression and cell-specific localization of COX-1, COX-2, microsomal prostaglandin E synthase-1 (mPGES-1 and two of the receptors for PGE2, EP1 and EP2, were examined by immunoblotting (IB and immunohistochemistry (IHC. Results The results are in line with earlier studies demonstrating an increase of COX-2 in AC compared to the normal ovary, B and BL tumours. Increased expressions were also observed for COX-1, mPGES-1 and EP-1 which all were significantly (p 1 was increased in stage III while no significant alterations were demonstrated for COX-1, mPGES-1 or EP2 for stage. IHC revealed staining of the tumour cells, but also increase of COX-1, COX-2, mPGES-1 and EP1–2 in the stromal compartment of AC (grades: moderately-, poorly- and undifferentiated. This observation suggests interactions between tumour cells and stromal cells (fibroblasts, immune cells, e.g. paracrine signalling mediated by growth factors, cytokines and possibly PGs. Conclusion The increases of COX-1, COX-2, mPGES-1 and EP1–2 in epithelial ovarian cancer, supports the hypothesis that PGE2-synthesis and signalling are of importance for malignant transformation and progression. The

  13. E2F5 status significantly improves malignancy diagnosis of epithelial ovarian cancer

    KAUST Repository

    Kothandaraman, Narasimhan

    2010-02-24

    Background: Ovarian epithelial cancer (OEC) usually presents in the later stages of the disease. Factors, especially those associated with cell-cycle genes, affecting the genesis and tumour progression for ovarian cancer are largely unknown. We hypothesized that over-expressed transcription factors (TFs), as well as those that are driving the expression of the OEC over-expressed genes, could be the key for OEC genesis and potentially useful tissue and serum markers for malignancy associated with OEC.Methods: Using a combination of computational (selection of candidate TF markers and malignancy prediction) and experimental approaches (tissue microarray and western blotting on patient samples) we identified and evaluated E2F5 transcription factor involved in cell proliferation, as a promising candidate regulatory target in early stage disease. Our hypothesis was supported by our tissue array experiments that showed E2F5 expression only in OEC samples but not in normal and benign tissues, and by significantly positively biased expression in serum samples done using western blotting studies.Results: Analysis of clinical cases shows that of the E2F5 status is characteristic for a different population group than one covered by CA125, a conventional OEC biomarker. E2F5 used in different combinations with CA125 for distinguishing malignant cyst from benign cyst shows that the presence of CA125 or E2F5 increases sensitivity of OEC detection to 97.9% (an increase from 87.5% if only CA125 is used) and, more importantly, the presence of both CA125 and E2F5 increases specificity of OEC to 72.5% (an increase from 55% if only CA125 is used). This significantly improved accuracy suggests possibility of an improved diagnostics of OEC. Furthermore, detection of malignancy status in 86 cases (38 benign, 48 early and late OEC) shows that the use of E2F5 status in combination with other clinical characteristics allows for an improved detection of malignant cases with sensitivity

  14. Common Genetic Variation In Cellular Transport Genes and Epithelial Ovarian Cancer (EOC Risk.

    Directory of Open Access Journals (Sweden)

    Ganna Chornokur

    Full Text Available Defective cellular transport processes can lead to aberrant accumulation of trace elements, iron, small molecules and hormones in the cell, which in turn may promote the formation of reactive oxygen species, promoting DNA damage and aberrant expression of key regulatory cancer genes. As DNA damage and uncontrolled proliferation are hallmarks of cancer, including epithelial ovarian cancer (EOC, we hypothesized that inherited variation in the cellular transport genes contributes to EOC risk.In total, DNA samples were obtained from 14,525 case subjects with invasive EOC and from 23,447 controls from 43 sites in the Ovarian Cancer Association Consortium (OCAC. Two hundred seventy nine SNPs, representing 131 genes, were genotyped using an Illumina Infinium iSelect BeadChip as part of the Collaborative Oncological Gene-environment Study (COGS. SNP analyses were conducted using unconditional logistic regression under a log-additive model, and the FDR q<0.2 was applied to adjust for multiple comparisons.The most significant evidence of an association for all invasive cancers combined and for the serous subtype was observed for SNP rs17216603 in the iron transporter gene HEPH (invasive: OR = 0.85, P = 0.00026; serous: OR = 0.81, P = 0.00020; this SNP was also associated with the borderline/low malignant potential (LMP tumors (P = 0.021. Other genes significantly associated with EOC histological subtypes (p<0.05 included the UGT1A (endometrioid, SLC25A45 (mucinous, SLC39A11 (low malignant potential, and SERPINA7 (clear cell carcinoma. In addition, 1785 SNPs in six genes (HEPH, MGST1, SERPINA, SLC25A45, SLC39A11 and UGT1A were imputed from the 1000 Genomes Project and examined for association with INV EOC in white-European subjects. The most significant imputed SNP was rs117729793 in SLC39A11 (per allele, OR = 2.55, 95% CI = 1.5-4.35, p = 5.66x10-4.These results, generated on a large cohort of women, revealed associations between inherited cellular

  15. Study of microsatellite instability in epithelial ovarian tumors%上皮性卵巢癌中微卫星不稳定的研究

    Institute of Scientific and Technical Information of China (English)

    卢媛; 刘惜时; 王跃祥; 宋后燕; Nanbert ZHONG

    2006-01-01

    Objective: To evaluate the frequency of MSI in epithelial ovarian tumors and its relationship with clinicopathologic features. Methods: Ninety fresh specimens of epithelial ovarian tumors, including 74 primary and 16 secondary tumors, were collected. Microsatellite analysis was carried out using 5 mono- and dinucleotide markers from the National Cancer Institute Consensus Panel by fluorescence-labeled polymerase chain reaction. Results: Of 90 epithelial ovarian tumors analyzed, 18 demonstrated a high level of microsatellite instability (MSI-H), 30 demonstrated a low level of microsatellite instability (MSI-L), and the remaining 42 exhibited microsatellite stability (MSS). Frequency of microsatellite instability (MSI) at loci BAT-25 was higher than that at any other loci. No correlation was found between MSI level and patient age, tumor type, tumor differentiation (P>0.05). But the microsatellite instability-high phenotype correlates with clinical stage.It tended to occur more frequently in early-stage tumors (P=0.03). Conclusion: The frequent MSI in epithelial ovarian tumors suggests that it is an early event to involve in the development of epithelial ovarian tumors.

  16. Insights into the field carcinogenesis of ovarian cancer based on the nanocytology of endocervical and endometrial epithelial cells

    Science.gov (United States)

    Damania, Dhwanil; Roy, Hemant K.; Kunte, Dhananja; Hurteau, Jean A.; Subramanian, Hariharan; Cherkezyan, Lusik; Krosnjar, Nela; Shah, Maitri; Backman, Vadim

    2013-01-01

    Ovarian cancer ranks fifth in cancer fatalities among American women. Although curable at early stages with surgery, most women are diagnosed with symptoms of late-stage metastatic disease. Moreover, none of the current diagnostic techniques are clinically recommended for at-risk women as they preferentially target low-grade tumors (which do not affect longevity) and fail to capture early signatures of more lethal serous tumors which originate in the fimbrae region of the fallopian tubes. Hence, the early detection of ovarian cancer is challenging given the current strategy. Recently, our group has developed a novel optical imaging technique, partial wave spectroscopic (PWS) microscopy, that can quantify the nanoscale macromolecular density fluctuations within biological cells via a biomarker, disorder strength (Ld). Using the concept of field carcinogenesis, we propose a method of detecting ovarian cancer by PWS assessment of endometrial and endocervical columnar cells. The study includes 26 patients (controls = 15, cancer = 11) for endometrium and 23 (controls = 13, cancer = 10) for endocervix. Our results highlight a significant increase in Ld (% fold-increase > 50%, P-value < 0.05) for columnar epithelial cells obtained from cancer patients compared to controls for both endocervix and endometrium. Overall, the quantification of field carcinogenic events in the endometrium and the novel observation of its extension to the cervix are unique findings in the understanding of ovarian field carcinogenesis. We further show independent validation of the presence of cervical field carcinogenesis with mico-RNA expression data. PMID:23436651

  17. Phase III trial of carboplatin plus paclitaxel with or without gemcitabine in first-line treatment of epithelial ovarian cancer

    DEFF Research Database (Denmark)

    du Bois, Andreas; Herrstedt, Jørn; Hardy-Bessard, Anne-Claire;

    2010-01-01

    One attempt to improve long-term survival in patients with advanced ovarian cancer was thought to be the addition of more non-cross-resistant drugs to platinum-paclitaxel combination regimens. Gemcitabine was among the candidates for a third drug....

  18. ESR1/SYNE1 polymorphism and invasive epithelial ovarian cancer risk: an Ovarian Cancer Association Consortium study

    DEFF Research Database (Denmark)

    Doherty, Jennifer A; Rossing, Mary Anne; Cushing-Haugen, Kara L

    2010-01-01

    containing, nuclear envelope 1 (SYNE1), which is involved in nuclear organization and structural integrity, function of the Golgi apparatus, and cytokinesis. An isoform encoded by SYNE1 has been reported to be downregulated in ovarian and other cancers. rs2295190 was genotyped in an additional 12 studies...

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

    Institute of Scientific and Technical Information of China (English)

    Genhai Zhu; Lan Hong; Shengtan Wang; Zhaoxin Yang; Chunying Chen; Shixuan Wang

    2015-01-01

    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 cel line OVCAR3 was grown in subcutaneous tissues and the tumor tissues were orthotopical y 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 orthotopical y implanted. Bmi-1 and EZH2 expression levels were lower in proximal paraneoplastic tissue samples than in cancer tissue samples (P 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.

  20. Linalool-Incorporated Nanoparticles as a Novel Anticancer Agent for Epithelial Ovarian Carcinoma.

    Science.gov (United States)

    Han, Hee Dong; Cho, Young-Jae; Cho, Sung Keun; Byeon, Yeongseon; Jeon, Hat Nim; Kim, Hye-Sun; Kim, Byoung-Gie; Bae, Duk-Soo; Lopez-Berestein, Gabriel; Sood, Anil K; Shin, Byung Cheol; Park, Yeong-Min; Lee, Jeong-Won

    2016-04-01

    Although cytotoxic chemotherapy is widely used against epithelial ovarian cancer (EOC), adverse side effects and emergence of resistance can limit its utility. Therefore, new drugs with systemic delivery platforms are urgently needed for this disease. In this study, we developed linalool-incorporated nanoparticles (LIN-NP) as a novel anticancer agent. We prepared LIN-NPs by the self-assembly water-in-oil-in-water (w/o/w) emulsion method. LIN-NP-mediated cytotoxicity and apoptosis was assessed in EOC cells, and the role of reactive oxygen species (ROS) generation as the mechanism of action was evaluated. In addition, therapeutic efficacy of LIN-NP was assessed in cell lines and patient-derived xenograft (PDX) models for EOC. LIN-NPs had significant cytotoxicity and apoptotic activity against EOC cells, including A2780, HeyA8, and SKOV3ip1. LIN-NP treatment increased apoptosis in EOC cells through ROS generation and a subsequent decrease in mitochondrial membrane potential and increase in caspase-3 levels. In addition, 100 mg/kg LIN-NPs significantly decreased tumor weight in the HeyA8 (P < 0.001) and SKOV3ip1 (P = 0.006) in vivo models. Although treatment with 50 mg/kg LIN-NP did not decrease tumor weight compared with the control group, combination treatment with paclitaxel significantly decreased tumor weight compared with paclitaxel alone in SKOV3ip1 xenografts (P = 0.004) and the patient-derived xenograft model (P = 0.020). We have developed LIN-NPs that induce ROS generation as a novel anticancer agent for EOC. These findings have broad applications for cancer therapy. Mol Cancer Ther; 15(4); 618-27. ©2016 AACR.

  1. MicroRNA-302b Suppresses Human Epithelial Ovarian Cancer Cell Growth by Targeting RUNX1

    Directory of Open Access Journals (Sweden)

    Tingting Ge

    2014-12-01

    Full Text Available Background: The microRNA (miR-302 family functions as a tumor suppressor in human cancer. However, its role in epithelial ovarian carcinoma (EOC remains unknown. Here, we investigated the role of miR-302b and its target gene RUNX1 in EOC. Methods: The expression levels of miR-302b and RUNX1 were assessed by quantitative real-time PCR and western blotting. The effects of ectopic expression of miR-302b were evaluated by the MTT assay, colony forming assay and flow cytometry. RUNX1 was identified as a target of miR-302b and their interaction was confirmed by luciferase activity assays, RUNX1 silencing and overexpression of a RUNX1 mutant construct lacking the 3′UTR. The effect of miR-302b on the suppression of tumor growth was investigated in vivo in a xenograft mouse model. Results: MiR-302b levels were markedly decreased in EOC specimens. Ectopic expression of miR-302b in EOC cells inhibited cell proliferation and colony formation, induced G0/G1 arrest, and promoted apoptosis. RUNX1 was identified as a direct target of miR-302b, and knockdown of RUNX1 inhibited cell growth in a manner similar to miR-302b overexpression, whereas introduction of a 3′UTR mutant of RUNX1 reversed the suppressive effect of miR-302b. Furthermore, miR-302b overexpression led to the inactivation of the STAT3 signaling pathway in EOC cells and inhibited tumor growth in a xenograft mouse model. Conclusions: MiR-302b functions as a tumor suppressor in EOC by targeting RUNX1 and modulating the activity of the STAT3 signaling pathway.

  2. Skeletal Muscle Depletion and Markers for Cancer Cachexia Are Strong Prognostic Factors in Epithelial Ovarian Cancer.

    Directory of Open Access Journals (Sweden)

    Stefanie Aust

    Full Text Available Tumor cachexia is an important prognostic parameter in epithelial ovarian cancer (EOC. Tumor cachexia is characterized by metabolic and inflammatory disturbances. These conditions might be reflected by body composition measurements (BCMs ascertained by pre-operative computed tomography (CT. Thus, we aimed to identify the prognostically most relevant BCMs assessed by pre-operative CT in EOC patients.We evaluated muscle BCMs and well established markers of nutritional and inflammatory status, as well as clinical-pathological parameters in 140 consecutive patients with EOC. Furthermore, a multiplexed inflammatory marker panel of 25 cytokines was used to determine the relationship of BCMs with inflammatory markers and patient's outcome. All relevant parameters were evaluated in uni- and multivariate survival analysis.Muscle attenuation (MA-a well established BCM parameter-is an independent prognostic factor for survival in multivariate analysis (HR 2.25; p = 0.028. Low MA-reflecting a state of cachexia-is also associated with residual tumor after cytoreductive surgery (p = 0.046 and with an unfavorable performance status (p = 0.015. Moreover, MA is associated with Eotaxin and IL-10 out of the 25 cytokine multiplex marker panel in multivariate linear regression analysis (p = 0.021 and p = 0.047, respectively.MA-ascertained by routine pre-operative CT-is an independent prognostic parameter in EOC patients. Low MA is associated with the inflammatory, as well as the nutritional component of cachexia. Therefore, the clinical value of pre-operative CT could be enhanced by the assessment of MA.

  3. MiR-101 suppresses the epithelial-to-mesenchymal transition by targeting ZEB1 and ZEB2 in ovarian carcinoma.

    Science.gov (United States)

    Guo, Fei; Cogdell, David; Hu, Limei; Yang, Da; Sood, Anil K; Xue, Fengxia; Zhang, Wei

    2014-05-01

    Ovarian carcinoma is the most lethal gynecologic malignancy; the majority of patients succumb to the disease within 5 years of diagnosis. The poor survival rate is attributed to diagnosis at advanced stage, when the tumor has metastasized. The epithelial-to-mesenchymal transition (EMT) is a necessary step toward metastatic tumor progression. Through integrated computational analysis, we recently identified a master microRNA (miRNA) network that includes miR-101 and regulates EMT in ovarian carcinoma. In the present study, we characterized the functions of miR-101. Using reporter gene assays, we demonstrated that miR-101 suppressed the expression of the E-cadherin repressors ZEB1 and ZEB2 by directly targeting the 3'-untranslated region (3'UTR) of both ZEB1 and ZEB2. Introduction of miR-101 significantly inhibited EMT and cell migration and invasion. Introducing cDNAs of ZEB1 and ZEB2 without 3'UTR abrogated miR-101-induced EMT alteration, respectively. Our findings showed that miR-101 represents a redundant mechanism for the miR-200 family that regulates EMT through two major E-cadherin transcriptional repressors.

  4. Cystathionine beta-synthase (CBS contributes to advanced ovarian cancer progression and drug resistance.

    Directory of Open Access Journals (Sweden)

    Sanjib Bhattacharyya

    Full Text Available BACKGROUND: Epithelial ovarian cancer is the leading cause of gynecologic cancer deaths. Most patients respond initially to platinum-based chemotherapy after surgical debulking, however relapse is very common and ultimately platinum resistance emerges. Understanding the mechanism of tumor growth, metastasis and drug resistant relapse will profoundly impact the therapeutic management of ovarian cancer. METHODS/PRINCIPAL FINDINGS: Using patient tissue microarray (TMA, in vitro and in vivo studies we report a role of of cystathionine-beta-synthase (CBS, a sulfur metabolism enzyme in ovarian carcinoma. We report here that the expression of cystathionine-beta-synthase (CBS, a sulfur metabolism enzyme, is common in primary serous ovarian carcinoma. The in vitro effects of CBS silencing can be reversed by exogenous supplementation with the GSH and H2S producing chemical Na2S. Silencing CBS in a cisplatin resistant orthotopic model in vivo by nanoliposomal delivery of CBS siRNA inhibits tumor growth, reduces nodule formation and sensitizes ovarian cancer cells to cisplatin. The effects were further corroborated by immunohistochemistry that demonstrates a reduction of H&E, Ki-67 and CD31 positive cells in si-RNA treated as compared to scrambled-RNA treated animals. Furthermore, CBS also regulates bioenergetics of ovarian cancer cells by regulating mitochondrial ROS production, oxygen consumption and ATP generation. This study reports an important role of CBS in promoting ovarian tumor growth and maintaining drug resistant phenotype by controlling cellular redox behavior and regulating mitochondrial bioenergetics. CONCLUSION: The present investigation highlights CBS as a potential therapeutic target in relapsed and platinum resistant ovarian cancer.

  5. Advancing ovarian folliculometry with selective plane illumination microscopy

    Science.gov (United States)

    Lin, Hsiao-Chun Amy; Dutta, Rahul; Mandal, Subhamoy; Kind, Alexander; Schnieke, Angelika; Razansky, Daniel

    2016-12-01

    Determination of ovarian status and follicle monitoring are common methods of diagnosing female infertility. We evaluated the suitability of selective plane illumination microscopy (SPIM) for the study of ovarian follicles. The large field of view and fast acquisition speed of our SPIM system enables rendering of volumetric image stacks from intact whole porcine ovarian follicles, clearly visualizing follicular features including follicle volume and average diameter (70 μm-2.5 mm), their spherical asymmetry parameters, size of developing cumulus oophorus complexes (40 μm-110 μm), and follicular wall thickness (90 μm-120 μm). Follicles at all developmental stages were identified. A distribution of the theca thickness was measured for each follicle, and a relationship between these distributions and the stages of follicular development was discerned. The ability of the system to non-destructively generate sub-cellular resolution 3D images of developing follicles, with excellent image contrast and high throughput capacity compared to conventional histology, suggests that it can be used to monitor follicular development and identify structural abnormalities indicative of ovarian ailments. Accurate folliculometric measurements provided by SPIM images can immensely help the understanding of ovarian physiology and provide important information for the proper management of ovarian diseases.

  6. Bevacizumab for advanced ovarian cancer treatment. A GRADE based approach

    Directory of Open Access Journals (Sweden)

    Giovanni L. Pappagallo

    2013-03-01

    Full Text Available Background: in advanced ovarian cancer, over the last 10 years no studies have demonstrated more appropriate therapeutic options compared to the current standard Carboplatin-Paclitaxel (Cb-P regimen. Two phase III randomized studies (GOG-218 36 and ICON-7 37 have recently demonstrated the efficacy of bevacizumab (recombinant monoclonal antibody that binds with a high affinity to VEGF-A in adjunct to Cb-P, with 12-15 months maintenance treatment.Methods: the quality of evidence provided was assessed by the use of the GRADE method. Each outcome (deemed to be essential for the purpose of evaluation of the intervention was assessed to express the degree of confidence in the entity of the beneficial and/or harmful effects of the intervention. Thus, limitations in the quality of conducting the studies (risk of bias, direct applicability/relevance of results to the target population, and precision of results were taken into account.Results: the GOG-218 and the ICON7 study (high-risk subgroup demonstrated with MODERATE confidence an improvement in critical outcomes PFS and OS, with an absolute reduction of 96 (GOG-218 – 103 (ICON-7 episodes of progression, and 40 (GOG-218 – 135 (ICON-7 deaths per 1 000 patients. A marked increase in risk of hypertension of Grade ≥3 was observed, with an absolute increase of 59 episodes per 1 000 patients in the ICON-7 study, and 157 episodes in the GOG-218 study, respectively, the majority of which were controlled by means of appropriate treatment. The increased risk of other adverse events considered was negligible.Conclusions: the positive effects produced should be viewed as taking prevalence over the negative effects (FAVOURABLE benefit/harm ratio.

  7. Functional polymorphisms in the TERT promoter are associated with risk of serous epithelial ovarian and breast cancers.

    Directory of Open Access Journals (Sweden)

    Jonathan Beesley

    Full Text Available Genetic variation at the TERT-CLPTM1L locus at 5p15.33 is associated with susceptibility to several cancers, including epithelial ovarian cancer (EOC. We have carried out fine-mapping of this region in EOC which implicates an association with a single nucleotide polymorphism (SNP within the TERT promoter. We demonstrate that the minor alleles at rs2736109, and at an additional TERT promoter SNP, rs2736108, are associated with decreased breast cancer risk, and that the combination of both SNPs substantially reduces TERT promoter activity.

  8. Panitumumab and pegylated liposomal doxorubicin in platinum-resistant epithelial ovarian cancer with KRAS wild-type

    DEFF Research Database (Denmark)

    Dahl Steffensen, Karina; Waldstrøm, Marianne; Lund, Bente

    , and head and neck cancer. No previous studies have evaluated the effect of panitumumab in OC based on KRAS mutation status. Methods: Eligibility criteria are confirmed stage I-IV primary epithelial ovarian/fallopian/peritoneal cancer patients with progression either during or within 6 months after end...... to a total of 33 patients. At present, 15 patients have been enrolled. The primary endpoint is to investigate the response rate in platinum-resistant, KRAS wild- type OC patients treated with PLD supplemented with panitumumab. Translational research is included as a secondary endpoint and tumor tissue...

  9. HE4 as a predictor of adjuvant chemotherapy resistance and survival in patients with epithelial ovarian cancer

    DEFF Research Database (Denmark)

    Aarenstrup Karlsen, Mona; Høgdall, Claus; Nedergaard, Lotte

    2016-01-01

    The aim of this study was to investigate the value of serum human epididymis protein 4 (HE4) and HE4 tissue protein expression to predict tumor resistance to adjuvant chemotherapy, progression-free survival (PFS), and overall survival in patients with epithelial ovarian cancer (EOC). Consecutive...... inclusion of 198 patients diagnosed with EOC was conducted. Blood samples were collected prior to surgery and tissue samples during surgery. Patient data were registered prospectively in the Danish Gynecologic Cancer Database. The association between serum HE4 and HE4 tissue protein expression, resistance...... significantly (p tissue protein expression...

  10. Relationship between the Expression of Thymidylate Synthase,Thymidine Phosphorylase and Dihydropyrimidine Dehydrogenase and Survival in Epithelial Ovarian Cancer

    Institute of Scientific and Technical Information of China (English)

    王常玉; 翁艳洁; 王鸿雁; 石英; 马丁

    2010-01-01

    The mRNA and protein expression of thymidylate synthase (TS), thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) and their relationship with prognosis were investigated. Real-time quantitative RT-PCR (Taqman) was used to detect the mRNA expression of TS, TP and DPD in formalin-fixed and paraffin-embedded 106 samples of epithelial ovarian cancer and 29 normal ovaries. A TATA box-binding protein (TBP) was used as an endogenous reference gene. A relationship between TS, TP, DPD expression a...

  11. [Initial management of advanced ovarian cancer: What radiological, pathological and surgical information are important for optimal therapeutic strategy?].

    Science.gov (United States)

    Heudel, Pierre-Etienne; Selle, Frédéric; Morice, Philippe; Rouzier, Roman; Taieb, Sophie; Devouassoux-Shisheboran, Mojgan; Genestie, Catherine; Balleyguier, Corinne; Ray-Coquard, Isabelle

    2015-09-01

    Because the majority of patients present advanced disease at diagnosis, the management of epithelial ovarian cancer needs specialist multidisciplinary teamwork. Expertise in surgery, chemotherapy, imaging and histopathology is essential to achieve optimum outcomes. Computed tomography scans are routinely used to determine the extent of disease and to aid in surgical planning. The histologic classification is crucial to plan the best therapeutic strategy and to define the prognosis of disease. Pathological prognostic factors, such as degree of differentiation, FIGO-stage, and histological type have to be described. This report is fundamental to assessing prognosis and selection of appropriate treatment strategy. An adequate staging procedure is an extensive staging by an experienced gynecological oncologist, exploring the entire upper abdomen, and the pelvic and para-aortic lymph node regions to define the Peritoneal Cancer Index (PCI). The final assessment is the completeness of cytoreduction (CC) score, which is an assessment of residual disease after a maximal surgical effort. Initial management of advanced ovarian cancer is best provided by a specialist multidisciplinary team, including a radiologist, a pathologist, a gynecologic oncologist and a medical oncologist.

  12. Polymorphism in the IL18 gene and epithelial ovarian cancer in non-Hispanic white women

    DEFF Research Database (Denmark)

    Palmieri, R.T.; Wilson, M.A.; Iversen, E.S.;

    2008-01-01

    Over 22,000 cases of ovarian cancer were diagnosed in 2007 in the United States, but only a fraction of them can be attributed to mutations in highly penetrant genes such as BRCA1. To determine whether low-penetrance genetic variants contribute to ovarian cancer risk, we genotyped 1,536 single nu...

  13. The ErbB signalling pathway : protein expression and prognostic value in epithelial ovarian cancer

    NARCIS (Netherlands)

    de Graeff, P.; Crijns, A.P.; ten Hoor, K.A.; Klip, H.G.; Hollema, H.; Oien, K.; Bartlett, J.M.; Wisman, G.B.; de Bock, G.H.; de Vries, E.G.; de Jong, S.; van der Zee, A.G.

    2008-01-01

    Ovarian cancer is the most frequent cause of death from gynaecological cancer in the Western world. Current prognostic factors do not allow reliable prediction of response to chemotherapy and survival for individual ovarian cancer patients. Epidermal growth factor receptor (EGFR) and HER-2/neu are f

  14. Association of ERCC1 protein expression to platinum resistance in epithelial ovarian cancer

    DEFF Research Database (Denmark)

    Dahl Steffensen, Karina; Waldstrøm, Marianne; Jakobsen, Anders

    was to investigate if immunohistochemical expression of ERCC1 protein was associated with resistance to standard combination carboplatin and paclitaxel chemotherapy in newly diagnosed ovarian cancer patients. Methods: Formalin-fixed, paraffin-embedded tissue sections from 101 patients with newly diagnosed ovarian...

  15. The Potential Mechanisms Underlying Aspirin-induced Inhibition of Ovarian Tumor Cell Growth

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    1 IntroductionOvarian cancer remains the most lethal disease of the gynecological cancers. Owing to the lack of an effective screening approach combined with inadequate therapeutic approach for advanced disease, fewer than 25% of ovarian cancers are identified at an early curable stage. Thus these make ovarian cancer a strong candidate for chemoprevention. In 2001, Akhmedkhanov et al. demonstrated a 2-3 folds decrease in epithelial ovarian cancer associated with Aspirin use. These epidemiological observatio...

  16. SERPINB3 in the chicken model of ovarian cancer: a prognostic factor for platinum resistance and survival in patients with epithelial ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Whasun Lim

    Full Text Available Serine protease inhibitors (SERPINs appear to be ubiquitously expressed in a variety of species and play important roles in pivotal physiological processes such as angiogenesis, immune responses, blood coagulation and fibronolysis. Of these, squamous cell carcinoma antigen 1 (SCCA1, also known as a SERPINB3, was first identified in squamous cell carcinoma tissue from the cervix of women. However, there is little known about the SERPINB3 expression in human epithelial ovarian cancer (EOC. Therefore, in the present study, we investigated the functional role of SERPINB3 gene in human EOC using chickens, the most relevant animal model. In 136 chickens, EOC was found in 10 (7.4%. SERPINB3 mRNA was induced in cancerous, but not normal ovaries of chickens (P<0.01, and it was abundant only in the glandular epithelium of cancerous ovaries of chickens. Further, several microRNAs, specifically miR-101, miR-1668 and miR-1681 were discovered to influence SERPINB3 expression via its 3'-UTR which suggests that post-transcriptional regulation influences SERPINB3 expression in chickens. SERPINB3 protein was localized predominantly to the glandular epithelium in cancerous ovaries of chickens, and it was abundant in the nucleus of both chicken and human ovarian cancer cell lines. In 109 human patients with EOC, 15 (13.8%, 66 (60.6% and 28 (25.7% patients showed weak, moderate and strong expression of SERPINB3 protein, respectively. Strong expression of SERPINB3 protein was a prognostic factor for platinum resistance (adjusted OR; odds ratio, 5.94; 95% Confidence Limits, 1.21-29.15, and for poor progression-free survival (PFS; adjusted HR; hazard ratio, 2.07; 95% CI; confidence interval, 1.03-4.41. Therefore, SERPINB3 may play an important role in ovarian carcinogenesis and be a novel biomarker for predicting platinum resistance and a poor prognosis for survival in patients with EOC.

  17. Phytoestrogen consumption from foods and supplements and epithelial ovarian cancer risk: a population-based case control study

    Directory of Open Access Journals (Sweden)

    Paddock Lisa E

    2011-09-01

    Full Text Available Abstract Background While there is extensive literature evaluating the impact of phytoestrogen consumption on breast cancer risk, its role on ovarian cancer has received little attention. Methods We conducted a population-based case-control study to evaluate phytoestrogen intake from foods and supplements and epithelial ovarian cancer risk. Cases were identified in six counties in New Jersey through the New Jersey State Cancer Registry. Controls were identified by random digit dialing, CMS (Centers for Medicare and Medicaid Service lists, and area sampling. A total of 205 cases and 390 controls were included in analyses. Unconditional logistic regression analyses were conducted to examine associations with total phytoestrogens, as well as isoflavones (daidzein, genistein, formononetin, and glycitein, lignans (matairesinol, lariciresinol, pinoresinol, secoisolariciresinol, and coumestrol. Results No statistically significant associations were found with any of the phytoestrogens under evaluation. However, there was a suggestion of an inverse association with total phytoestrogen consumption (from foods and supplements, with an odds ratio (OR of 0.62 (95% CI: 0.38-1.00; p for trend: 0.04 for the highest vs. lowest tertile of consumption, after adjusting for reproductive covariates, age, race, education, BMI, and total energy. Further adjustment for smoking and physical activity attenuated risk estimates (OR: 0.66; 95% CI: 0.41-1.08. There was little evidence of an inverse association for isoflavones, lignans, or coumestrol. Conclusions This study provided some suggestion that phytoestrogen consumption may decrease ovarian cancer risk, although results did not reach statistical significance.

  18. Identification of glucocorticoid-induced leucine zipper as a key regulator of tumor cell proliferation in epithelial ovarian cancer

    Directory of Open Access Journals (Sweden)

    Fernandez Hervé

    2009-10-01

    Full Text Available Abstract Background Little is known about the molecules that contribute to tumor progression of epithelial ovarian cancer (EOC, currently a leading cause of mortality from gynecological malignancies. Glucocorticoid-Induced Leucine Zipper (GILZ, an intracellular protein widely expressed in immune tissues, has been reported in epithelial tissues and controls some of key signaling pathways involved in tumorigenesis. However, there has been no report on GILZ in EOC up to now. The objectives of the current study were to examine the expression of GILZ in EOC and its effect on tumor cell proliferation. Results GILZ expression was measured by immunohistochemical staining in tissue sections from 3 normal ovaries, 7 benign EOC and 50 invasive EOC. GILZ was not detected on the surface epithelium of normal ovaries and benign tumors. In contrast, it was expressed in the cytoplasm of tumor cells in 80% EOC specimens. GILZ immunostaining scores correlated positively to the proliferation marker Ki-67 (Spearman test in univariate analysis, P P Conclusion The present study is the first to identify GILZ as a molecule produced by ovarian cancer cells that promotes cell cycle progression and proliferation. Our findings clearly indicate that GILZ activates AKT, a crucial signaling molecule in tumorigenesis. GILZ thus appears as a potential key molecule in EOC.

  19. Associations between genes for killer immunoglobulin-like receptors and their ligands in patients with epithelial ovarian cancer.

    Science.gov (United States)

    Giebel, Sebastian; Boratyn-Nowicka, Agnieszka; Karabon, Lidia; Jedynak, Anna; Pamula-Pilat, Jolanta; Tecza, Karolina; Kula, Dorota; Kowal, Monika; Frydecka, Irena; Grzybowska, Ewa

    2014-06-01

    Killer immunoglobulin-like receptors (KIRs) regulate function of NK cells and subsets of T cells. HLA class I molecules are ligands for inhibitory KIRs while specificity of activating KIRs is mainly unknown. Both KIR and HLA genotypes are highly polymorphic. In this study we analyzed associations of KIR and KIR ligand genes with the incidence and clinical course of epithelial ovarian cancer. DNA of 142 patients was analyzed for KIR genes and 103 samples were typed for HLA class I. Control group consisted of 200 healthy individuals, including 83 women, analyzed separately. The frequency of KIR genes in patients and controls were comparable. HLA-C group 1 (ligand for KIR2DL2/3) was more frequent in patients than in controls (86.4% vs. 67.5%, p=0.002). The frequency of KIR2DS4fl was higher in patients with endometrioid cancer (72.3%) compared with other histological subtypes (36.5%, p=0.004) and controls (29.5%, p=0.0001). KIR and KIR ligand genotype did not influence significantly the clinical course of the disease. We conclude that the genotype of KIR ligands is strongly associated with the incidence of epithelial ovarian cancer while KIR2DS4fl confers susceptibility to endometrioid subtype of the disease.

  20. Evaluation of whether serum tumor markers in patients with epithelial ovarian carcinoma change following chemotherapy

    Institute of Scientific and Technical Information of China (English)

    LI Xiao-ping; XU Qi-ying; WANG Jian-liu; WANG Shi-jun; ZHAO Yan; WEI Li-hui

    2012-01-01

    Background Phenotypic and genotypic heterogeneity is a known feature of many cancers.Whether serum tumor marker kinds vary and change following chemotherapy is still unclear.The aim of this study was to investigate whether there is a change in the expression of serum tumor markers following chemotherapy,and the potential clinical significance in patients with epithelial ovarian carcinoma (EOC) or primary serous peritoneal carcinoma (PSPC).Methods Samples were collected before surgery,during chemotherapy and during follow-up for enzyme-linked immunosorbent assay (ELISA)-based evaluation of serum CA-125,CA19-9 and CP2 levels in patients with EOC or PSPC who had received primary debulking surgery followed by adjuvant chemotherapy.In total,72 patients were examined,including 37 patients with recurrent lesions and 35 patients receiving first-line chemotherapy.Results In 35 de novo patients,20% (7/35) demonstrated a significant changed serum tumor marker kinds among whom the patients with mucinous carcinoma (57.1%,4/7) showed resistance to chemotherapy.In the 37 recurrent patients,51.4% (19/37) had changed serum tumor markers,of whom 57.9% (11/19) presented with serous carcinoma.There was no significant difference in median progression-free survival or overall survival in patients with drug-sensitive or drug-resistant recurrence in patients with changed tumor marker kinds relative to those with unchanged markers.However,for patients with changed serum tumor markers there was a trend towards prolonged survival compared with the unchanged serum tumor marker group.In the 17 patients with secondary recurrence,37.5% (6/17) had changed tumor marker levels.The ratios of CA-125/CP2 and CA-125/CA19-9 were significantly different after either chemotherapy or recurrence.Conclusions Serum tumor marker expression in patients with EOC or PSPC may change after chemotherapy or recurrence,indicating that in addition to the markers that are abnormal before surgery,those markers

  1. Does the use of diagnostic PET/CT cause stage migration in patients with primary advanced ovarian cancer?

    DEFF Research Database (Denmark)

    Risum, S; Høgdall, C; Loft, Annika

    2010-01-01

    To investigate if the use of diagnostic FDG-PET/CT leads to stage migration in patients with advanced ovarian cancer and to evaluate the prognostic significance of FDG-PET/CT.......To investigate if the use of diagnostic FDG-PET/CT leads to stage migration in patients with advanced ovarian cancer and to evaluate the prognostic significance of FDG-PET/CT....

  2. Promoter hypermethylation of FANCF and outcome in advanced ovarian cancer

    NARCIS (Netherlands)

    S.L. Lim; P. Smith; N. Syed; C. Coens (Corneel); H. Wong; M. van der Burg (Mirjam); P. Szlosarek; T. Crook (Tim); J.A. Green

    2008-01-01

    textabstractThe Fanconi gene family has a role in DNA repair and inactivation of FANCF has been proposed as a mechanism of sensitisation to platinum chemotherapy. This study sought to confirm this hypothesis in cell lines and a large series of ovarian cancer samples. Promoter methylation was assesse

  3. Insights into the field carcinogenesis of ovarian cancer based on the nanocytology of endocervical and endometrial epithelial cells.

    Science.gov (United States)

    Damania, Dhwanil; Roy, Hemant K; Kunte, Dhananja; Hurteau, Jean A; Subramanian, Hariharan; Cherkezyan, Lusik; Krosnjar, Nela; Shah, Maitri; Backman, Vadim

    2013-09-01

    Ovarian cancer ranks fifth in cancer fatalities among American women. Although curable at early stages with surgery, most women are diagnosed with symptoms of late-stage metastatic disease. Moreover, none of the current diagnostic techniques are clinically recommended for at-risk women as they preferentially target low-grade tumors (which do not affect longevity) and fail to capture early signatures of more lethal serous tumors which originate in the fimbrae region of the fallopian tubes. Hence, the early detection of ovarian cancer is challenging given the current strategy. Recently, our group has developed a novel optical imaging technique, partial wave spectroscopic (PWS) microscopy, that can quantify the nanoscale macromolecular density fluctuations within biological cells via a biomarker, disorder strength (Ld ). Using the concept of field carcinogenesis, we propose a method of detecting ovarian cancer by PWS assessment of endometrial and endocervical columnar cells. The study includes 26 patients (controls = 15, cancer = 11) for endometrium and 23 (controls = 13, cancer = 10) for endocervix. Our results highlight a significant increase in Ld (% fold-increase > 50%, p-value < 0.05) for columnar epithelial cells obtained from cancer patients compared to controls for both endocervix and endometrium. Overall, the quantification of field carcinogenic events in the endometrium and the novel observation of its extension to the cervix are unique findings in the understanding of ovarian field carcinogenesis. We further show independent validation of the presence of cervical field carcinogenesis with micro-RNA expression data.

  4. Treatment Option Overview (Ovarian Epithelial, Fallopian Tube, and Primary Peritoneal Cancer)

    Science.gov (United States)

    ... peritoneal cancer include pain or swelling in the abdomen. Ovarian, fallopian tube, or peritoneal cancer may not ... swelling, or a feeling of pressure in the abdomen or pelvis. Vaginal bleeding that is heavy or ...

  5. ATM, ATR and DNA-PKcs expressions correlate to adverse clinical outcomes in epithelial ovarian cancers

    Directory of Open Access Journals (Sweden)

    Tarek M.A. Abdel-Fatah

    2014-12-01

    General significance: The data presented here provides evidence that ATM, ATR and DNA-PKcs involved in DDR are not only promising biomarkers but are also rational targets for personalized therapy in ovarian cancer.

  6. Randomised comparison of cisplatin with cyclophosphamide/cisplatin and with cyclophosphamide/doxorubicin/cisplatin in advanced ovarian cancer. Gruppo Interegionale Cooperativo Oncologico Ginecologia.

    Science.gov (United States)

    1987-08-15

    565 patients with stage III-IV epithelial ovarian cancer were randomly assigned to receive cisplatin (P), cyclophosphamide and cisplatin (CP), or cyclophosphamide, doxorubicin, and cisplatin (CAP). Data on 531 patients were analysed. Treatment with CAP resulted in a significantly higher overall (complete and partial) response rate (66 vs 56 vs 49% for CAP, CP, and P, respectively), but the rate of complete surgical response for the three treatment arms was similar (26, 21, and 20%). Size of residual tumour after first surgery and Karnofsky index were the best predictors of complete remission. Survival and disease-free survival were not significantly different in the three arms, although progression-free survival was significantly longer after CAP. However, tumour size, cell type, and Karnofsky index, but not therapy, were independent predictors for survival. Haematological toxicity was highest with CAP. The addition of cyclophosphamide or doxorubicin and cyclophosphamide to cisplatin does not substantially increase the number of potentially curable, advanced ovarian cancer patients.

  7. Identification of a potential ovarian cancer stem cell gene expression profile from advanced stage papillary serous ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Vinod Vathipadiekal

    Full Text Available Identification of gene expression profiles of cancer stem cells may have significant implications in the understanding of tumor biology and for the design of novel treatments targeted toward these cells. Here we report a potential ovarian cancer stem cell gene expression profile from isolated side population of fresh ascites obtained from women with high-grade advanced stage papillary serous ovarian adenocarcinoma. Affymetrix U133 Plus 2.0 microarrays were used to interrogate the differentially expressed genes between side population (SP and main population (MP, and the results were analyzed by paired T-test using BRB-ArrayTools. We identified 138 up-regulated and 302 down-regulated genes that were differentially expressed between all 10 SP/MP pairs. Microarray data was validated using qRT-PCR and17/19 (89.5% genes showed robust correlations between microarray and qRT-PCR expression data. The Pathway Studio analysis identified several genes involved in cell survival, differentiation, proliferation, and apoptosis which are unique to SP cells and a mechanism for the activation of Notch signaling is identified. To validate these findings, we have identified and isolated SP cells enriched for cancer stem cells from human ovarian cancer cell lines. The SP populations were having a higher colony forming efficiency in comparison to its MP counterpart and also capable of sustained expansion and differentiation in to SP and MP phenotypes. 50,000 SP cells produced tumor in nude mice whereas the same number of MP cells failed to give any tumor at 8 weeks after injection. The SP cells demonstrated a dose dependent sensitivity to specific γ-secretase inhibitors implicating the role of Notch signaling pathway in SP cell survival. Further the generated SP gene list was found to be enriched in recurrent ovarian cancer tumors.

  8. Reproductive and hormone-related risk factors for epithelial ovarian cancer by histologic pathways, invasiveness and histologic subtypes : Results from the EPIC cohort

    NARCIS (Netherlands)

    Fortner, Renée T.; Ose, Jennifer; Merritt, Melissa A.; Schock, Helena; Tjønneland, Anne; Hansen, Louise; Overvad, Kim; Dossus, Laure; Clavel-Chapelon, Françoise; Baglietto, Laura; Boeing, Heiner; Trichopoulou, Antonia; Benetou, Vassiliki; Lagiou, Pagona; Agnoli, Claudia; Mattiello, Amalia; Masala, Giovanna; Tumino, Rosario; Sacerdote, Carlotta; Bueno-De-Mesquita, H. B.; Onland-Moret, N. Charlotte; Peeters, Petra H.; Weiderpass, Elisabete; Torhild Gram, Inger; Duell, Eric J.; Larrañaga, Nerea; Ardanaz, Eva; Sánchez, María José; Chirlaque, M. D.; Brändstedt, Jenny; Idahl, Annika; Lundin, Eva; Khaw, Kay Tee; Wareham, Nick; Travis, Ruth C.; Rinaldi, Sabina; Romieu, Isabelle; Gunter, Marc J.; Riboli, Elio; Kaaks, Rudolf

    2015-01-01

    Whether risk factors for epithelial ovarian cancer (EOC) differ by subtype (i.e., dualistic pathway of carcinogenesis, histologic subtype) is not well understood; however, data to date suggest risk factor differences. We examined associations between reproductive and hormone-related risk factors for

  9. The VEGF pathway and the AKT/mTOR/p70S6K1 signalling pathway in human epithelial ovarian cancer

    NARCIS (Netherlands)

    X.B. Trinh; W.A.A. Tjalma; P.B. Vermeulen; G. van den Eynden; I. van der Auwera; S.J. van Laere (Steven); J. Helleman (Jozien); P.M.J.J. Berns (Els); L.Y. Dirix (Luc); P.A. van Dam

    2009-01-01

    textabstractVascular endothelial growth factor (VEGF)-A inhibitors exhibit unseen high responses and toxicity in recurrent epithelial ovarian cancer suggesting an important role for the VEGF/VEGFR pathway. We studied the correlation of VEGF signalling and AKT/mTOR signalling. Using a tissue microarr

  10. Involvement of MINK, a Ste20 Family Kinase, in Ras Oncogene-Induced Growth Arrest in Human Ovarian Surface Epithelial Cells

    NARCIS (Netherlands)

    Nicke, B.; Bastien, J.; Khanna, S.J.; Warne, P.H.; Cowling, V.; Cook, S.J.; Peters, G.; Delpuech, O.; Schulze, A.; Berns, K.; Mullenders, J.; Beijersbergen, R.L.; Bernards, R.A.; Ganesan, T.S.; Downward, J.; Hancock, D.C.

    2005-01-01

    The ability of activated Ras to induce growth arrest of human ovarian surface epithelial (HOSE) cells via induction of the cyclin-dependent kinase inhibitor p21WAF1/CIP1 has been used to screen for Ras pathway signaling components using a library of RNA interference (RNAi) vectors targeting the kino

  11. Aberrant promoter methylation and gene expression of H-cadherin gene is associated with tumor progression and recurrence in epithelial ovarian carcinoma

    Directory of Open Access Journals (Sweden)

    Rahul Bhagat

    2014-01-01

    Full Text Available Background: Loss of expression of cadherins by promoter hypermethylation has been described in many epithelial cancers, and it may play a role in tumor cell invasion and metastasis. Previously, we reported that E-cadherin gene is frequently methylated in epithelial ovarian cancer. Aim: The aim of this study was to compare the promoter hypermethylation of H-cadherin gene in ovarian epithelial neoplasms to better understand the role of epigenetic silencing in carcinogenesis. Materials and Methods: We examined the promoter methylation of the H-cadherin gene in 134 epithelial ovarian carcinomas (EOC, 23 low malignant potential (LMP tumors, 26 benign cystadenomas and 15 normal ovarian tissues. Methylation was investigated by methylation specific polymerase chain reaction (MSP and the results confirmed by bisulfite DNA sequencing. Relative gene expression of H-cadherin was done using quantitative reverse transcriptase PCR on 51 EOC cases, 9 LMP tumors, 7 benign cystadenomas with 5 normal ovarian tissues. Results: Aberrant methylation of H-cadherin was present in 20 of 134 (15% carcinoma cases, 2 of 23 (09% LMP tumors and 1 of 26 (4% benign cystadenomas. No methylation was observed in any of the normal ovarian tissues. The mRNA expression level of H-cadherin was significantly down-regulated in EOC and LMP tumors than the corresponding normal tissues, whereas the expression level was normal in benign cystadenomas. A significant correlation of H-cadherin promoter methylation was observed with reduced gene expression in EOC. The prevalence of H-cadherin methylation was associated significantly with stage, histopathological grade, and menopausal status of the patient. H-cadherin methylation also had significant association with recurrence and differentiation of tumor. Conclusion: Our findings suggest an association between H-cadherin methylation, tumor progression and recurrence in EOC.

  12. Statin as a Combined Therapy for Advanced-Stage Ovarian Cancer: A Propensity Score Matched Analysis

    Directory of Open Access Journals (Sweden)

    Hong-Yu Chen

    2016-01-01

    Full Text Available Background. Despite the great achievements in the treatment of advanced-stage ovarian cancer, it is still a severe condition with an unfavorable 5-year survival rate. Statins have been suggested to reduce the risk of several cancers beyond their cholesterol-lowing effects. However, the prognostic significance of statins in patients with advanced-stage ovarian cancer remains controversial. Methods. A retrospective study was performed to evaluate the association between statin intake and overall survival (OS among patients with advanced-stage ovarian cancer. Patients who underwent cytoreductive surgery followed by courses of intravenous chemotherapy were matched through a propensity score analysis. Results. A total of 60 propensity-matched patients were included. Women in statin group showed a similar OS than the nonstatin counterparts (P=0.966, whereas residual tumor was significantly associated with better OS (P=0.013 and was an independent factor that associated with OS (P=0.002, hazard ratio = 5.460, and 95% confidence interval: 1.894 to 15.742 in multivariable analysis. Conclusions. Our results suggested that statin usage was not associated with improved OS in patients with advanced-stage ovarian cancer undergoing surgery and chemotherapy. Considering the retrospective nature and the relative small sample size of the study, further prospective studies and random control trials are needed.

  13. Expression of CD44v6 and Its Association with Prognosis in Epithelial Ovarian Carcinomas

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    Dang-xia Zhou

    2012-01-01

    Full Text Available The aim of this study was to evaluate CD44v6 protein expression and its prognostic value of CD44v6 in ovarian carcinoma. The expression of CD44v6 was analyzed in 62 patients with ovarian carcinoma by immunohistochemical method. The data obtained were analyzed by univariate and multivariate analyses. The present study clearly demonstrates that tumor tissues from 41 (66.1% patients showed positive expression with CD44v6. The expression of CD44v6 was significantly correlated with histological type, FIGO stage and histological grade of ovarian carcinomas. Concerning the prognosis, the survival period of patients with CD44v6 positive was shorter than that of patients with CD44v6 negative (36.6% versus 66.7%, 5-year survival, P<0.05. Univariate analysis showed that CD44v6 expression, histological type, FIGO stage and histological grade were associated with 5-year survival, and CD44v6 expression was associated with histological type, FIGO stage and histological grade and 5-year survival. In multivariate analysis, using the COX-regression model, CD44v6 expression was important prognostic factor. In conclusion, these results suggest that CD44v6 may be related to histological type, FIGO stage and histological grade of ovarian carcinomas, and CD44v6 may be an important molecular marker for poor prognosis in ovarian carcinomas.

  14. The O-Linked Glycome and Blood Group Antigens ABO on Mucin-Type Glycoproteins in Mucinous and Serous Epithelial Ovarian Tumors.

    Directory of Open Access Journals (Sweden)

    Varvara Vitiazeva

    Full Text Available Mucins are heavily O-glycosylated proteins where the glycosylation has been shown to play an important role in cancer. Normal epithelial ovarian cells do not express secreted mucins, but their abnormal expression has previously been described in epithelial ovarian cancer and may relate to tumor formation and progression. The cyst fluids were shown to be a rich source for acidic glycoproteins. The study of these proteins can potentially lead to the identification of more effective biomarkers for ovarian cancer.In this study, we analyzed the expression of the MUC5AC and the O-glycosylation of acidic glycoproteins secreted into ovarian cyst fluids. The samples were obtained from patients with serous and mucinous ovarian tumors of different stages (benign, borderline, malignant and grades. The O-linked oligosaccharides were released and analyzed by negative-ion graphitized carbon Liquid Chromatography (LC coupled to Electrospray Ionization tandem Mass Spectrometry (ESI-MSn. The LC-ESI-MSn of the oligosaccharides from ovarian cyst fluids displayed differences in expression of fucose containing structures such as blood group ABO antigens and Lewis-type epitopes.The obtained data showed that serous and mucinous benign adenomas, mucinous low malignant potential carcinomas (LMPs, borderline and mucinous low-grade carcinomas have a high level of blood groups and Lewis type epitopes. In contrast, this type of fucosylated structures were low abundant in the high-grade mucinous carcinomas or in serous carcinomas. In addition, the ovarian tumors that showed a high level of expression of blood group antigens also revealed a strong reactivity towards the MUC5AC antibody. To visualize the differences between serous and mucinous ovarian tumors based on the O-glycosylation, a hierarchical cluster analysis was performed using mass spectrometry average compositions (MSAC.Mucinous benign and LMPs along with mucinous low-grade carcinomas appear to be different from

  15. ABCA Transporter Gene Expression and Poor Outcome in Epithelial Ovarian Cancer

    DEFF Research Database (Denmark)

    Hedditch, Ellen L; Gao, Bo; Russell, Amanda J

    2014-01-01

    -wide association study. Impact of short interfering RNA-mediated gene suppression was determined by colony forming and migration assays. Association with survival was assessed with Kaplan-Meier analysis and log-rank tests. All statistical tests were two-sided. RESULTS: Associations with outcome were observed...... with ABC transporters of the "A" subfamily, but not with multidrug transporters. High-level expression of ABCA1, ABCA6, ABCA8, and ABCA9 in primary tumors was statistically significantly associated with reduced survival in serous ovarian cancer patients. Low levels of ABCA5 and the C-allele of rs536009...... cancer cell growth and migration in vitro, and statin treatment reduced ovarian cancer cell migration. CONCLUSIONS: Expression of ABCA transporters was associated with poor outcome in serous ovarian cancer, implicating lipid trafficking as a potentially important process in EOC....

  16. Single nucleotide polymorphisms in the TP53 region and susceptibility to invasive epithelial ovarian cancer

    DEFF Research Database (Denmark)

    Schildkraut, Joellen M; Goode, Ellen L; Clyde, Merlise A;

    2009-01-01

    The p53 protein is critical for multiple cellular functions including cell growth and DNA repair. We assessed whether polymorphisms in the region encoding TP53 were associated with risk of invasive ovarian cancer. The study population includes a total of 5,206 invasive ovarian cancer cases (2......,829 of which were serous) and 8,790 controls from 13 case-control or nested case-control studies participating in the Ovarian Cancer Association Consortium (OCAC). Three of the studies performed independent discovery investigations involving genotyping of up to 23 single nucleotide polymorphisms (SNP......) in the TP53 region. Significant findings from this discovery phase were followed up for replication in the other OCAC studies. Mixed effects logistic regression was used to generate posterior median per allele odds ratios (OR), 95% probability intervals (PI), and Bayes factors (BF) for genotype associations...

  17. c-Yes enhances tumor migration and invasion via PI3K/AKT pathway in epithelial ovarian cancer.

    Science.gov (United States)

    Jin, Yunfeng; Huang, Menghui; Wang, Yingying; Yi, Changying; Deng, Yan; Chen, Yannan; Jiang, Lifei; Wang, Juan; Shen, Qin; Liu, Rong; QinghuaXi

    2016-08-01

    Overexpression of c-Yes has been noted to correlation with several human cancers. However, the effects of c-Yes on epithelial ovarian cancer (EOC) development remain unclear. The aim of this study is going to prove the effects of c-Yes and related mechanisms in proliferation, metastasis and invasion of EOC. Immunohistochemical analysis was performed in 119 human EOC samples, and the data was correlated with clinic pathologic features. Furthermore, western blot analysis is performed for c-Yes in EOC samples and cell lines to evaluate their protein levels and molecular interaction. Kaplan-Meier survival analysis shows that the strong expression of c-Yes exhibited a significant correlation with poor prognosis in human EOC (PYes by shRNA inhibited the ability of migration and invasion in EOC cells via the PI3K/AKT pathway. In a word, these results suggested that c-Yes plays an important role in migration and invasion of EOC.

  18. Tumour-specific HMG-CoAR is an independent predictor of recurrence free survival in epithelial ovarian cancer

    LENUS (Irish Health Repository)

    Brennan, Donal J

    2010-04-01

    Abstract Background Our group previously reported that tumour-specific expression of the rate-limiting enzyme in the mevalonate pathway, 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR) is associated with more favourable tumour parameters and a good prognosis in breast cancer. In the present study, the prognostic value of HMG-CoAR expression was examined in tumours from a cohort of patients with primary epithelial ovarian cancer. Methods HMG-CoAR expression was assessed using immunohistochemistry (IHC) on tissue microarrays (TMA) consisting of 76 ovarian cancer cases, analysed using automated algorithms to develop a quantitative scoring model. Kaplan Meier analysis and Cox proportional hazards modelling were used to estimate the risk of recurrence free survival (RFS). Results Seventy-two tumours were suitable for analysis. Cytoplasmic HMG-CoAR expression was present in 65% (n = 46) of tumours. No relationship was seen between HMG-CoAR and age, histological subtype, grade, disease stage, estrogen receptor or Ki-67 status. Patients with tumours expressing HMG-CoAR had a significantly prolonged RFS (p = 0.012). Multivariate Cox regression analysis revealed that HMG-CoAR expression was an independent predictor of improved RFS (RR = 0.49, 95% CI (0.25-0.93); p = 0.03) when adjusted for established prognostic factors such as residual disease, tumour stage and grade. Conclusion HMG-CoAR expression is an independent predictor of prolonged RFS in primary ovarian cancer. As HMG-CoAR inhibitors, also known as statins, have demonstrated anti-neoplastic effects in vitro, further studies are required to evaluate HMG-CoAR expression as a surrogate marker of response to statin treatment, especially in conjunction with current chemotherapeutic regimens.

  19. Tumour-specific HMG-CoAR is an independent predictor of recurrence free survival in epithelial ovarian cancer.

    LENUS (Irish Health Repository)

    Brennan, Donal J

    2010-01-01

    BACKGROUND: Our group previously reported that tumour-specific expression of the rate-limiting enzyme in the mevalonate pathway, 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR) is associated with more favourable tumour parameters and a good prognosis in breast cancer. In the present study, the prognostic value of HMG-CoAR expression was examined in tumours from a cohort of patients with primary epithelial ovarian cancer. METHODS: HMG-CoAR expression was assessed using immunohistochemistry (IHC) on tissue microarrays (TMA) consisting of 76 ovarian cancer cases, analysed using automated algorithms to develop a quantitative scoring model. Kaplan Meier analysis and Cox proportional hazards modelling were used to estimate the risk of recurrence free survival (RFS). RESULTS: Seventy-two tumours were suitable for analysis. Cytoplasmic HMG-CoAR expression was present in 65% (n = 46) of tumours. No relationship was seen between HMG-CoAR and age, histological subtype, grade, disease stage, estrogen receptor or Ki-67 status. Patients with tumours expressing HMG-CoAR had a significantly prolonged RFS (p = 0.012). Multivariate Cox regression analysis revealed that HMG-CoAR expression was an independent predictor of improved RFS (RR = 0.49, 95% CI (0.25-0.93); p = 0.03) when adjusted for established prognostic factors such as residual disease, tumour stage and grade. CONCLUSION: HMG-CoAR expression is an independent predictor of prolonged RFS in primary ovarian cancer. As HMG-CoAR inhibitors, also known as statins, have demonstrated anti-neoplastic effects in vitro, further studies are required to evaluate HMG-CoAR expression as a surrogate marker of response to statin treatment, especially in conjunction with current chemotherapeutic regimens.

  20. Acid ceramidase (AC)--a key enzyme of sphingolipid metabolism--correlates with better prognosis in epithelial ovarian cancer.

    Science.gov (United States)

    Hanker, Lars Christian; Karn, Thomas; Holtrich, Uwe; Gätje, Regine; Rody, Achim; Heinrich, Tomas; Ruckhäberle, Eugen; Engels, Knut

    2013-05-01

    Acid ceramidase (AC), a key enzyme of sphingolipid metabolism, seems to play an important role in cancer progression. The objective of this study was to explore the expression of AC in ovarian cancer and its impact on prognosis. Expression analysis of AC in n=112 ovarian cancer patients was performed by immunohistochemical analysis of primary paraffin-embedded tumor samples. The results were scored on the basis of the staining intensity and percentage of positive tumor cells, resulting in an immunoreactive score from 0 to 12. These results were correlated to clinical and pathologic characteristics and survival. AC expression correlated significantly only with FIGO stage (0.047). In serous carcinoma, low level of AC was independently associated with reduced progression-free survival and overall survival of 12.0 mo [95% confidence interval (CI), 5.78-18.23] versus 18.1 mo (95% CI, 11.61-24.59; P=0.008) and 35.7 mo (95% CI, 22.24-47.16) versus 58.7 mo (95% CI, 36.48-80.91; P=0.032), respectively. In multivariate analysis, AC presents as an independent prognostic factor for progression-free survival (hazard ratio 1.88; 95% CI, 1.13-3.11; P=0.015). AC is a prognostic factor in epithelial ovarian cancer. Low AC expression can be associated with tumor progression in carcinoma of the ovaries. These results are in contrast to the concept of AC as a promoter for cancer progression. Nevertheless, they are supported by the lately discovered tumor-suppressing function of sphingosine, the enzymatic product of AC.

  1. Tumour-specific HMG-CoAR is an independent predictor of recurrence free survival in epithelial ovarian cancer

    Directory of Open Access Journals (Sweden)

    Gallagher William M

    2010-04-01

    Full Text Available Abstract Background Our group previously reported that tumour-specific expression of the rate-limiting enzyme in the mevalonate pathway, 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR is associated with more favourable tumour parameters and a good prognosis in breast cancer. In the present study, the prognostic value of HMG-CoAR expression was examined in tumours from a cohort of patients with primary epithelial ovarian cancer. Methods HMG-CoAR expression was assessed using immunohistochemistry (IHC on tissue microarrays (TMA consisting of 76 ovarian cancer cases, analysed using automated algorithms to develop a quantitative scoring model. Kaplan Meier analysis and Cox proportional hazards modelling were used to estimate the risk of recurrence free survival (RFS. Results Seventy-two tumours were suitable for analysis. Cytoplasmic HMG-CoAR expression was present in 65% (n = 46 of tumours. No relationship was seen between HMG-CoAR and age, histological subtype, grade, disease stage, estrogen receptor or Ki-67 status. Patients with tumours expressing HMG-CoAR had a significantly prolonged RFS (p = 0.012. Multivariate Cox regression analysis revealed that HMG-CoAR expression was an independent predictor of improved RFS (RR = 0.49, 95% CI (0.25-0.93; p = 0.03 when adjusted for established prognostic factors such as residual disease, tumour stage and grade. Conclusion HMG-CoAR expression is an independent predictor of prolonged RFS in primary ovarian cancer. As HMG-CoAR inhibitors, also known as statins, have demonstrated anti-neoplastic effects in vitro, further studies are required to evaluate HMG-CoAR expression as a surrogate marker of response to statin treatment, especially in conjunction with current chemotherapeutic regimens.

  2. Genomic activation of the EGFR and HER2-neu genes in a significant proportion of invasive epithelial ovarian cancers

    Directory of Open Access Journals (Sweden)

    Ghislain Vanessa

    2008-01-01

    Full Text Available Abstract Background The status of the EGFR and HER2-neu genes has not been fully defined in ovarian cancer. An integrated analysis of both genes could help define the proportion of patients that would potentially benefit from targeted therapies. Methods We determined the tumour mutation status of the entire tyrosine kinase (TK domain of the EGFR and HER2-neu genes in a cohort of 52 patients with invasive epithelial ovarian cancer as well as the gene copy number and protein expression of both genes in 31 of these patients by DGGE and direct sequecing, immunohistochemistry and Fluorescent in Situ Hybridisation (FISH. Results The EGFR was expressed in 59% of the cases, with a 2+/3+ staining intensity in 38%. HER2-neu expression was found in 35%, with a 2/3+ staining in 18%. No mutations were found in exons 18–24 of the TK domains of EGFR and HER2-neu. High polysomy of the EGFR gene was observed in 13% of the invasive epthelial cancers and amplification of the HER2-neu gene was found in 10% and correlated with a high expression level by immunohistochemistry. Mutations within the tyrosine kinase domain were not found in the entire TK domain of both genes, but have been found in very rare cases by others. Conclusion Genomic alteration of the HER2-neu and EGFR genes is frequent (25% in ovarian cancer. EGFR/HER2-neu targeted therapies should be investigated prospectively and specifically in that subset of patients.

  3. CYP1B1 enhances the resistance of epithelial ovarian cancer cells to paclitaxel in vivo and in vitro.

    Science.gov (United States)

    Zhu, Zhuangyan; Mu, Yaqin; Qi, Caixia; Wang, Jian; Xi, Guoping; Guo, Juncheng; Mi, Ruoran; Zhao, Fuxi

    2015-02-01

    Ovarian cancer (OC) is the most frequent cause of mortality among gynecological malignancies, with a 5-year survival rate of approximately 30%. The standard regimen for OC therapy includes a platinum agent combined with a taxane, to which the patients frequently acquire resistance. Resistance arises from the oxidation of anticancer drugs by CYP1B1, a cytochrome P450 enzyme overexpressed in malignant OC. The aim of the present study was to determine the role of CYP1B1 expression in the drug resistance of OC to the taxane, paclitaxel (PTX). Immunohistochemical staining was used to assess CYP1B1 expression in a panel of ovarian samples (53 primary cancer samples, 14 samples of metastastic cancer, 30 benign tumor samples and 19 normal tissue samples). Semi-quantitative RT-PCR was also performed to determine CYP1B1 expression in several OC cell lines. Finally, we used proliferation and toxicity assays, as well as a mouse xenograft model using nude mice to determine whether α-naphthoflavone (ANF), a CYP1B1 specific inhibitor, reduces resistance to PTX. CYP1B1 was overexpressed in the samples from primary and metastatic loci of epithelial ovarian cancers. In some cell lines, PTX induced CYP1B1 expression, which resulted in drug resistance. Exposure to ANF reduced drug resistance and enhanced the sensitivity of OC cells to PTX in vitro and in vivo. The expression profile of CYP1B1 suggests that it has the potential to be a useful diagnostic marker and prognostic factor for malignant OC. The inhibition of CYP1B1 expression by specific agents may provide a novel therapeutic strategy for the treatment of patients resistant to PTX and may improve the prognosis of these patients.

  4. Investigating impact of Vascular Endothelial Growth Factor Polymorphisms in Epithelial Ovarian Cancers: A Study in the Indian Population

    Science.gov (United States)

    Bhagat, Rahul; Chennagiri Srinivasamurthy, Premalata; Venketeshiah Reddihalli, Pallavi; Gawari, Ramesh

    2015-01-01

    Epithelial ovarian cancer is one of the increasingly incident malignancies that is notorious because of its evasiveness for early diagnosis and high mortality rates. Epithelial ovarian cancers are highly dependent on pathologic vasculature and Vascular Endothelial Growth Factor is known to be one of the most efficient angiogenic factors. Polymorphisms of the VEGF gene, in this study, were assessed for association with the malignancy and other clinico-pathological factors. 300 case samples and 320 age and mensus status matched controls were inculcated into the study. rs699947, rs833061, rs1570360, rs2010963, rs1413711 and rs3025039 were the six single nucleotide polymorphisms that were scrutinized. Genotyping was carried out by polymerase chain reaction and restriction fragment length polymorphism. rs 3025039 showed immense promise as a marker for disease aggression and recurrence and a factor for poor prognosis. rs699947 showed least association with the disease and clinico-pathologic factors studied. rs833061, rs 1570360 showed significant association with some clinico-pathological factors such as bilateral affliction of ovaries and post operative CA-125 levels. rs2010963 associated with presence of ascites in higher volumes. The SNPs under consideration showed no formidable linkage in our study samples. A haplotype analysis (excluding rs699947 and rs1413711) revealed 5 frontrunners being present in >85% of the population with TGGC and CGCC associating significantly as protective and risk factors respectively. These haplotypes showed a dose dependent additive effect of their seeming functionality. This study is unique and a first of its kind carried out in the Indian population of South-east Asia. PMID:26158818

  5. Annexin A3 Is a Potential Predictor of Platinum Resistance in Epithelial Ovarian Cancer Patients in a Prospective Cohort.

    Science.gov (United States)

    Jin, Ying; Feng, Li-Ping; Jiang, Xiang; Wang, Yong-Xue; Yin, Jie; Yang, Zi-Ping; Li, Yan; Pan, Ling-Ya

    2015-01-01

    Epithelial ovarian cancer (EOC) is the leading cause of death among gynecological malignancies and is rarely cured in the recurrent setting, mainly because of progressive chemoresistance, especially platinum resistance. In our previous studies, the platinum-resistance-related protein, annexin A3, was selected by comparative proteomics. In this study, we detected serum annexin A3 levels using a self-developed chemiluminescence immunoassay kit in a prospective EOC patient cohort. We also evaluated the capacity of serum annexin A3 levels to predict platinum resistance. Serum annexin A3 levels in healthy women exhibited a similar normal distribution (Z=0.723, P=0.673), allowing determination of a normal cutoff level of 0.11-1.45 ng/mL. Of the 89 EOC patients, 21 were platinum resistant and 68 were platinum sensitive. Residual disease after primary surgery (p=0.004) and serum annexin A3 levels (p=0.036) were both independent factors associated with platinum resistance. The AUC was 0.733 (95% confidence interval (CI), 0.627-0.823). The optimal cutoff value for serum annexin A3 levels was 2.05 ng/mL. Multivariate logistic analysis showed that expression of annexin A3 as assessed by immunohistochemistry (P=0.005) and residual tumor size (P=0.000) had a significant influence on platinum resistance. The AUC of ROC curve of annexin A3 expression by immunohistochemistry was 0.664 (95% CI, 0.554-0.763) and the cut off value was ">=moderate scores". In conclusion, we demonstrate that annexin A3 is a secreted protein that may be measured in the peripheral blood using a self-developed, chemiluminescence immunoassay kit. Serum annexin A3 levels may be a potential predictor of platinum resistance in epithelial ovarian cancer patients.

  6. Investigating impact of Vascular Endothelial Growth Factor Polymorphisms in Epithelial Ovarian Cancers: A Study in the Indian Population.

    Directory of Open Access Journals (Sweden)

    Bhaskari Janardhan

    Full Text Available Epithelial ovarian cancer is one of the increasingly incident malignancies that is notorious because of its evasiveness for early diagnosis and high mortality rates. Epithelial ovarian cancers are highly dependent on pathologic vasculature and Vascular Endothelial Growth Factor is known to be one of the most efficient angiogenic factors. Polymorphisms of the VEGF gene, in this study, were assessed for association with the malignancy and other clinico-pathological factors. 300 case samples and 320 age and mensus status matched controls were inculcated into the study. rs699947, rs833061, rs1570360, rs2010963, rs1413711 and rs3025039 were the six single nucleotide polymorphisms that were scrutinized. Genotyping was carried out by polymerase chain reaction and restriction fragment length polymorphism. rs 3025039 showed immense promise as a marker for disease aggression and recurrence and a factor for poor prognosis. rs699947 showed least association with the disease and clinico-pathologic factors studied. rs833061, rs 1570360 showed significant association with some clinico-pathological factors such as bilateral affliction of ovaries and post operative CA-125 levels. rs2010963 associated with presence of ascites in higher volumes. The SNPs under consideration showed no formidable linkage in our study samples. A haplotype analysis (excluding rs699947 and rs1413711 revealed 5 frontrunners being present in >85% of the population with TGGC and CGCC associating significantly as protective and risk factors respectively. These haplotypes showed a dose dependent additive effect of their seeming functionality. This study is unique and a first of its kind carried out in the Indian population of South-east Asia.

  7. Regulation of Murine Ovarian Epithelial Carcinoma by Vaccination against the Cytoplasmic Domain of Anti-Müllerian Hormone Receptor II

    Directory of Open Access Journals (Sweden)

    Cagri Sakalar

    2015-01-01

    Full Text Available Anti-Müllerian hormone receptor, type II (AMHR2, is a differentiation protein expressed in 90% of primary epithelial ovarian carcinomas (EOCs, the most deadly gynecologic malignancy. We propose that AMHR2 may serve as a useful target for vaccination against EOC. To this end, we generated the recombinant 399-amino acid cytoplasmic domain of mouse AMHR2 (AMHR2-CD and tested its efficacy as a vaccine target in inhibiting growth of the ID8 transplantable EOC cell line in C57BL/6 mice and in preventing growth of autochthonous EOCs that occur spontaneously in transgenic mice. We found that AMHR2-CD immunization of C57BL/6 females induced a prominent antigen-specific proinflammatory CD4+ T cell response that resulted in a mild transient autoimmune oophoritis that resolved rapidly with no detectable lingering adverse effects on ovarian function. AMHR2-CD vaccination significantly inhibited ID8 tumor growth when administered either prophylactically or therapeutically, and protection against EOC growth was passively transferred into naive recipients with AMHR2-CD-primed CD4+ T cells but not with primed B cells. In addition, prophylactic AMHR2-CD vaccination of TgMISIIR-TAg transgenic mice significantly inhibited growth of autochthonous EOCs and provided a 41.7% increase in mean overall survival. We conclude that AMHR2-CD vaccination provides effective immunotherapy of EOC with relatively benign autoimmune complications.

  8. Preoperative red cell distribution width and neutrophil-to-lymphocyte ratio predict survival in patients with epithelial ovarian cancer

    Science.gov (United States)

    Li, Zheng; Hong, Na; Robertson, Melissa; Wang, Chen; Jiang, Guoqian

    2017-01-01

    Several parameters of preoperative complete blood count (CBC) and inflammation-associated blood cell markers derived from them have been reported to correlate with prognosis in patients with epithelial ovarian cancer (EOC), but their prognostic importance and optimal cutoffs are still needed be elucidated. Clinic/pathological parameters, 5-year follow-up data and preoperative CBC parameters were obtained retrospectively in 654 EOC patients underwent primary surgery at Mayo Clinic. Cutoffs for neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) were optimized by receiver operating characteristic (ROC) curve. Prognostic significance for overall survival (OS) and recurrence free survival (RFS) were determined by Cox proportional hazards models and Kaplan-Meier method. Associations of RDW and NLR with clinic/pathological parameters were analyzed using non-parametric tests. RDW with cutoff 14.5 and NLR with cutoff 5.25 had independent prognostic significance for OS, while combined RDW and NLR scores stratified patients into low (RDW-low and NLR-low), intermediate (RDW-high or NLR-high) and high risk (RDW-high and NLR-high) groups, especially in patients with high-grade serous ovarian cancer (HGSOC). Moreover, high NLR was associated with poor RFS as well. Elevated RDW was strongly associated with age, whereas high NLR was strongly associated with stage, preoperative CA125 level and ascites at surgery. PMID:28223716

  9. The relationship of platinum resistance and ERCC1 protein expression in epithelial ovarian cancer

    DEFF Research Database (Denmark)

    Steffensen, Karina Dahl; Waldstrøm, Marianne; Jakobsen, Anders

    2009-01-01

    : Formalin-fixed, paraffin-embedded tissue sections from 101 patients with newly diagnosed ovarian cancer were used for immunohistochemical staining for the ERCC1 protein. All patients received carboplatin-paclitaxel combination chemotherapy. RESULTS: Excision repair cross-complementation group 1 enzyme...

  10. Trefoil factor 3 expression in epithelial ovarian cancer exerts a minor effect on clinicopathological parameters

    Science.gov (United States)

    Hoellen, Friederike; Kostara, Athina; Karn, Thomas; Holtrich, Uwe; El-Balat, Ahmed; Otto, Mike; Rody, Achim; Hanker, Lars C.

    2016-01-01

    The role of trefoil factor 3 (intestinal) (TFF3) has been analyzed in numerous cancers, such as breast and gastrointestinal cancer, and has been associated with poor prognosis. However, the role of TFF3 in ovarian cancers is not clear. Expression analysis of TFF3 in 91 ovarian cancer patients was performed by immunohistochemistry of primary paraffin-embedded tumor samples. The results were scored according to staining intensity and percentage of positive tumor cells resulting in an immune-reactive score (IRS) of 0–12. These results were correlated with clinicopathological characteristics and survival. TFF3 expression in our patient cohort exhibited a tendency towards improved overall and progression-free survival (PFS). In TFF3-positive serous and high-grade serous ovarian cancers, the median PFS was 27.6 months [95% confidence interval (CI): 0–55.7] vs. 15.2 months in TFF3-negative tumors (95% CI: 13.8–16.6) (P=0.183). The median overall survival was 53.9 months in TFF3-positive tumors (95% CI: Non-applicable) vs. 44.4 months in TFF3-negative cases (95% CI: 30.5–58.3) (P=0.36). TFF3 negativity was significantly associated with higher tumor grade (P=0.05). Based on our results, further studies are required in order to elucidate whether survival and chemosensitivity are affected by TFF3 expression in ovarian cancer.

  11. Common Genetic Variation in Circadian Rhythm Genes and Risk of Epithelial Ovarian Cancer (EOC)

    DEFF Research Database (Denmark)

    Jim, Heather S L; Lin, Hui-Yi; Tyrer, Jonathan P;

    2016-01-01

    ,722 controls and a validation set of 44,308 samples including 18,174 (10,316 serous) cases and 26,134 controls from 43 studies participating in the Ovarian Cancer Association Consortium (OCAC). Analysis of genotype data from 36 genotyped SNPs and 4600 imputed SNPs indicated that the most significant...

  12. Evaluation of candidate stromal epithelial cross-talk genes identifies association between risk of serous ovarian cancer and TERT, a cancer susceptibility "hot-spot".

    Directory of Open Access Journals (Sweden)

    Sharon E Johnatty

    2010-07-01

    Full Text Available We hypothesized that variants in genes expressed as a consequence of interactions between ovarian cancer cells and the host micro-environment could contribute to cancer susceptibility. We therefore used a two-stage approach to evaluate common single nucleotide polymorphisms (SNPs in 173 genes involved in stromal epithelial interactions in the Ovarian Cancer Association Consortium (OCAC. In the discovery stage, cases with epithelial ovarian cancer (n=675 and controls (n=1,162 were genotyped at 1,536 SNPs using an Illumina GoldenGate assay. Based on Positive Predictive Value estimates, three SNPs-PODXL rs1013368, ITGA6 rs13027811, and MMP3 rs522616-were selected for replication using TaqMan genotyping in up to 3,059 serous invasive cases and 8,905 controls from 16 OCAC case-control studies. An additional 18 SNPs with Pper-alleleor=0.5. However genotypes at TERT rs7726159 were associated with ovarian cancer risk in the smaller, five-study replication study (Pper-allele=0.03. Combined analysis of the discovery and replication sets for this TERT SNP showed an increased risk of serous ovarian cancer among non-Hispanic whites [adj. ORper-allele 1.14 (1.04-1.24 p=0.003]. Our study adds to the growing evidence that, like the 8q24 locus, the telomerase reverse transcriptase locus at 5p15.33, is a general cancer susceptibility locus.

  13. Outcomes analysis of an alternative formulation of PEGylated liposomal doxorubicin in recurrent epithelial ovarian carcinoma during the drug shortage era

    Directory of Open Access Journals (Sweden)

    Berger JL

    2014-08-01

    Full Text Available Jessica L Berger, Ashlee Smith, Kristin K Zorn, Paniti Sukumvanich, Alexander B Olawaiye, Joseph Kelley, Thomas C Krivak Magee-Womens Hospital, University of Pittsburgh Medical Center, Division of Gynecologic Oncology, Pittsburgh, PA, USA Background: In response to the critical shortage of Doxil®, the US Food and Drug Administration (FDA allowed temporary importation of non-FDA-approved second-generation liposomal doxorubicin, Lipo-Dox®. Lipo-Dox utilizes a different liposomal particle than Doxil and demonstrates different pharmacokinetic properties. Its use has never been evaluated in a North American population. The objective of this study was to evaluate the efficacy and tolerability of Lipo-Dox at Magee-Womens Hospital, University of Pittsburgh Medical Center, for patients with recurrent epithelial ovarian cancer who were treated during the Doxil shortage. Methods: Patients treated with Lipo-Dox from January 2012 to December 2012 were identified retrospectively. Disease response was defined radiographically by RECIST (Response Evaluation Criteria in Solid Tumors or biochemically by CA-125 level if measurable disease was not present. Survival was defined from the start date of Lipo-Dox until the date of progression or death. Toxicity was assessed by the Gynecologic Oncology Group common toxicity criteria. Results: Eighteen patients with recurrent epithelial ovarian cancer who received Lipo-Dox were identified. These patients had a median of three prior treatment regimens. The median number of Lipo-Dox cycles given was 3.5 (range 1–8. No patients had a complete or partial response. Two patients had stable disease over a mean follow-up of 144.5 days. Fourteen patients had progressive disease, with a median time to progression of 82 days. Progression was based on CA-125 in four patients and RECIST in the remainder. Nine patients died from the disease. Conclusion: Although this represents a small, pretreated population, there were no clinical

  14. Signaling pathways related to multidrug resistance in epithelial ovarian cancer%上皮性卵巢癌多药耐药相关信号传导通路及其靶向药物研究进展

    Institute of Scientific and Technical Information of China (English)

    韦露薇; 李力

    2016-01-01

    卵巢癌是严重威胁女性生殖健康的肿瘤之一,死亡率居各类妇科肿瘤的首位。上皮性癌是卵巢癌中最常见的病理类型,近年来虽然手术及放化疗技术不断提高,但75%~80%晚期患者在治疗后仍出现复发或进展。多药耐药是导致上皮性卵巢癌治疗后复发、转移和死亡的重要原因,严重制约上皮性卵巢癌患者生存率的提高。信号传导通路是多药耐药的重要调控机制之一,目前对其作用机制的研究取得了一定进展,其靶向药物亦在临床各期试验获得了良好效果。本文拟对信号传导通路在上皮性卵巢癌多药耐药机制及目前相关靶向药物在临床研究进展进行综述,为其进一步在临床应用提供指导价值。%Ovarian cancer is a serious threat to women's reproductive health. Epithelial carcinoma is the most common pathological type of ovarian cancer. In addition, epithelial carcinoma demonstrates the highest mortality among all types of gynecological tumors. Despite the recent advances in surgery, radiation, and chemotherapy, recurrence or deterioration still occurs in 75%–80%of patients after treatment. Multidrug resistance is a major cause of post-treatment relapses, metastasis, and even death. This characteristic se-verely restricts the survival of patients with epithelial ovarian cancer. Signaling pathways are important regulatory mechanisms of mul-tidrug resistance. To date, research on the mechanisms of action of these pathways has progressed, and clinical trials on specific inhibi-tors obtained satisfactory results. This study explores the potential relationship between signaling pathways and multidrug resistance in epithelial ovarian cancer, as well as the current progress in clinical research on targeted drugs, to provide a theoretical basis for clini-cal applications.

  15. Comprehensive serum profiling for the discovery of epithelial ovarian cancer biomarkers.

    Directory of Open Access Journals (Sweden)

    Ping Yip

    Full Text Available FDA-cleared ovarian cancer biomarkers are limited to CA-125 and HE4 for monitoring and recurrence and OVA1, a multivariate panel consisting of CA-125 and four additional biomarkers, for referring patients to a specialist. Due to relatively poor performance of these tests, more accurate and broadly applicable biomarkers are needed. We evaluated the dysregulation of 259 candidate cancer markers in serum samples from 499 patients. Sera were collected prospectively at 11 monitored sites under a single well-defined protocol. All stages of ovarian cancer and common benign gynecological conditions were represented. To ensure consistency and comparability of biomarker comparisons, all measurements were performed on a single platform, at a single site, using a panel of rigorously calibrated, qualified, high-throughput, multiplexed immunoassays and all analyses were conducted using the same software. Each marker was evaluated independently for its ability to differentiate ovarian cancer from benign conditions. A total of 175 markers were dysregulated in the cancer samples. HE4 (AUC=0.933 and CA-125 (AUC=0.907 were the most informative biomarkers, followed by IL-2 receptor α, α1-antitrypsin, C-reactive protein, YKL-40, cellular fibronectin, CA-72-4 and prostasin (AUC>0.800. To improve the discrimination between cancer and benign conditions, a simple multivariate combination of markers was explored using logistic regression. When combined into a single panel, the nine most informative individual biomarkers yielded an AUC value of 0.950, significantly higher than obtained when combining the markers in the OVA1 panel (AUC 0.912. Additionally, at a threshold sensitivity of 90%, the combination of the top 9 markers gave 88.9% specificity compared to 63.4% specificity for the OVA1 markers. Although a blinded validation study has not yet been performed, these results indicate that alternative biomarker combinations might lead to significant improvements in the

  16. Mechanism of Ovarian Epithelial Tumor Predisposition in Individuals Carrying Germline BRCA1 Mutations

    Science.gov (United States)

    2006-12-01

    predisposition to neoplastic transformation. This hypothesis does not rule out a cell autonomous mechanism based on the idea that BRCA1 also functions as a...It seems unlikely that cells that are as different in their function and embryological origin as the ovarian surface mesothelium and the fallopian... Embryological Development of the Female Reproductive System (9 weeks) l i l l l i http://wwwtt :// . . . / i / it- l / l t / t t . t Mullerian Duct

  17. Identification of Ovarian Cancer Susceptibility Genes Involved in Stromal-Epithelial Interactions

    Science.gov (United States)

    2009-02-01

    Mayo Clinic (Ellen Goode)) by Mass Array for 22 SNPs in CSF1, DDR2 , FN1, ITGA6, ITGAV, LCN2, MMP26, MMP3, MMP7, PANX1, PLOD2, PODXL, PTEN, PTTG1,TERT...Ovarian Cancer Association Consortium, as well as a further 19 SNPs in PTTG1, CSF1, PLOD2, FGF2, TIMP3, DDR2 , FN1, MMP7, PANX1, PTEN, ITGAV and LCN2

  18. Maintenance Chemotherapy of Stage Ⅲ Epithelial Ovarian Carcinoma-Focusing on Individualized Maintenance Chemotherapy

    Institute of Scientific and Technical Information of China (English)

    Xiaodong Zhao; Yi Zhang; Qiao Zhang

    2005-01-01

    OBJECTIVE To investigate the role of maintenance chemotherapy on stage Ⅲ ovarian carcinoma.METHODS A retrospective analysis was conducted of 47 stage Ⅲ ovarian carcinoma patients with clinical complete remission after first-line chemotherapy. Among these patients, 21 cases were treated with maintenance chemotherapy, while the other 26 cases were free of treatment until progression. The 2 groups were compared with respect to progression-free survival (PFS) and overall survival(OS).RESULTS The median PFS and OS were not significantly different between the 2 groups. For those patients, in a subgroup of suboptimal surgery (residual disease >2 cm), the median PFS was 110 weeks and 56 weeks and the median OS was 223 weeks and 157 weeks for the maintenance and non-treated respectively. Both PFS and OS values favoured the maintenance group, P=0.004 and P=0.015 respectively. In a subgroup of optimal surgery (residual disease ≤2 cm), the differences were not significant.CONCLUSION Patients with stage Ⅲ ovarian carcinoma with clinical complete remission may benefit from maintenance chemotherapy, if the residual disease is >2 cm. To those with a residual disease ≤2 cm, the maintenance chemotherapy maybe of no value. So "individualized maintenance chemotherapy" should be conducted in the clinical setting.

  19. PARP Inhibitors in Epithelial Ovarian Cancer: State of Art and Perspectives of Clinical Research.

    Science.gov (United States)

    Gadducci, Angiolo; Guerrieri, Maria Elena

    2016-05-01

    Homologous recombination (HR) and base excision repair (BER) are two of the major DNA-repair pathways. The proteins encoded by breast-related cancer antigen (BRCA) and poly(adenosine diphosphate-ribose) polymerases (PARP) are involved in HR and BER, respectively. Tumors with HR deficiency, including those in BRCA mutation carriers, are sensitive to BER blockade via PARP inhibitors. These represent novel therapeutic tools for HR-deficient ovarian cancer, able to improve progression-free survival of women with recurrent, platinum-sensitive disease in response to recent platinum-based chemotherapy. More research is needed to assesses whether inhibitors of PARP have any role as maintenance treatment after first-line chemotherapy and as palliative treatment of platinum-resistant disease. Germline BRCA testing should be offered to all patients with ovarian cancer, regardless of age and family history. HR deficiency has been observed not only in germline BRCA mutation carriers, but also in patients with somatic mutations or epigenetic silencing of BRCA, and with loss of function of other genes. Half of all high-grade ovarian carcinomas are HR-deficient, and additional biological and clinical investigations are strongly warranted to identify patients with this subset of tumors.

  20. Expression of organic cation transporter SLC22A16 in human epithelial ovarian cancer: a possible role of the adriamycin importer.

    Science.gov (United States)

    Ota, Kyoko; Ito, Kiyoshi; Akahira, Jun-ichi; Sato, Naoko; Onogawa, Tohru; Moriya, Takuya; Unno, Michiaki; Abe, Takaaki; Niikura, Hitoshi; Takano, Tadao; Yaegashi, Nobuo

    2007-07-01

    The SLC22A16 is one of the newly isolated organic cation transporters, which is responsible for uptake and transport of adriamycin into cells. Adriamycin is considered to be an active agent for ovarian cancer. Recently, the benefit of adding adriamycin to the current standard regimen, paclitaxel and platinum, is evaluated to improve the outcome of patients with ovarian cancer. Therefore, we examined the expression of SLC22A16 in ovarian cancers. Twelve ovarian carcinoma cell lines were used for immunoblotting and reverse transcription-polymerase chain reaction to confirm the expression of SLC22A16 mRNA and protein. Five normal ovaries, 12 ovarian adenomas, and 94 ovarian cancer cases were obtained from patients after surgical therapy. The specimens were used for immunohistochemistry. The median value of relative SLC22A16 gene expression in cell lines derived from clear-cell adenocarcinoma was significantly higher than that in cell lines from other histologies (P < 0.001). Expression of SLC22A16 protein was also detected in cell lines derived from clear-cell adenocarcinoma. The SLC22A16 immunoreactivity was detected in 15 (16%) of 94 epithelial ovarian cancer, 1 (8.3%) of 12 benign adenomas, but 0 (0%) of 5 normal ovary cases. In ovarian cancer tissues, SLC22A16 immunoreactivity was detected in 2 (5%) of 38 serous adenocarcinoma, 1 (6.7%) of 15 endometrioid adenocarcinoma, 0 (0%) of 14 mucinous adenocarcinoma, and 12 (46.2%) of 26 clear-cell adenocarcinoma (P < 0.0001, clear-cell vs other histologies). In conclusion, SLC22A16 was abundantly expressed in clear-cell adenocarcinoma. Our results suggest that adriamycin-related chemicals that are taken up via SLC22A16 may have the potential to be effective against clear-cell adenocarcinoma.

  1. Development of A Mouse Model of Menopausal Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Elizabeth R. Smith

    2014-02-01

    Full Text Available Despite significant understanding of the genetic mutations involved in ovarian epithelial cancer and advances in genomic approaches for expression and mutation profiling of tumor tissues, several key questions in ovarian cancer biology remain enigmatic: the mechanism for the well-established impact of reproductive factors on ovarian cancer risk remains obscure; questions of the cell of origin of ovarian cancer continue to be debated; and the precursor lesion, sequence, or events in progression remain to be defined. Suitable mouse models should complement the analysis of human tumor tissues and may provide clues to these questions currently perplexing ovarian cancer biology.A potentially useful model is the germ cell-deficient Wv (white spotting variant mutant mouse line, which may be used to study the impact of menopausal physiology on the increased risk of ovarian cancer. The Wv mice harbor a point mutation in c-Kit that reduces the receptor tyrosine kinase activity to about 1-5% (it is not a null mutation. Homozygous Wv mutant females have a reduced ovarian germ cell reservoir at birth and the follicles are rapidly depleted upon reaching reproductive maturity, but other biological phenotypes are minimal and the mice have a normal life span. The loss of ovarian function precipitates changes in hormonal and metabolic activity that model features of menopause in humans. As a consequence of follicle depletion, the Wv ovaries develop ovarian tubular adenomas, a benign epithelial tumor corresponding to surface epithelial invaginations and papillomatosis that mark human ovarian aging. Ongoing work will test the possibility of converting the benign epithelial tubular adenomas into neoplastic tumors by addition of an oncogenic mutation, such as of Tp53, to model the genotype and biology of serous ovarian cancer.Model based on the Wv mice may have the potential to gain biological and etiological insights into ovarian cancer development and prevention.

  2. Chemotherapy of ovarian cancer in elderly patients

    Institute of Scientific and Technical Information of China (English)

    Tiffany A. Troso-Sandoval; Stuart M. Lichtman

    2015-01-01

    Epithelial ovarian cancer is primarily a disease of older women. Advanced age is risk factor for decreased survival. Optimal surgery and the safe and effective administration of chemotherapy are essential for prolonged progression-free and overall survival (OS). In this article, the available regimens in both the primary treatment and relapsed setting are reviewed.

  3. Variation in cell signaling protein expression may introduce sampling bias in primary epithelial ovarian cancer.

    Science.gov (United States)

    Mittermeyer, Gabriele; Malinowsky, Katharina; Beese, Christian; Höfler, Heinz; Schmalfeldt, Barbara; Becker, Karl-Friedrich; Avril, Stefanie

    2013-01-01

    Although the expression of cell signaling proteins is used as prognostic and predictive biomarker, variability of protein levels within tumors is not well studied. We assessed intratumoral heterogeneity of protein expression within primary ovarian cancer. Full-length proteins were extracted from 88 formalin-fixed and paraffin-embedded tissue samples of 13 primary high-grade serous ovarian carcinomas with 5-9 samples each. In addition, 14 samples of normal fallopian tube epithelium served as reference. Quantitative reverse phase protein arrays were used to analyze the expression of 36 cell signaling proteins including HER2, EGFR, PI3K/Akt, and angiogenic pathways as well as 15 activated (phosphorylated) proteins. We found considerable intratumoral heterogeneity in the expression of proteins with a mean coefficient of variation of 25% (range 17-53%). The extent of intratumoral heterogeneity differed between proteins (p<0.005). Interestingly, there were no significant differences in the extent of heterogeneity between phosphorylated and non-phosphorylated proteins. In comparison, we assessed the variation of protein levels amongst tumors from different patients, which revealed a similar mean coefficient of variation of 21% (range 12-48%). Based on hierarchical clustering, samples from the same patient clustered more closely together compared to samples from different patients. However, a clear separation of tumor versus normal tissue by clustering was only achieved when mean expression values of all individual samples per tumor were analyzed. While differential expression of some proteins was detected independently of the sampling method used, the majority of proteins only demonstrated differential expression when mean expression values of multiple samples per tumor were analyzed. Our data indicate that assessment of established and novel cell signaling proteins as diagnostic or prognostic markers may require sampling of serous ovarian cancers at several distinct

  4. Variation in cell signaling protein expression may introduce sampling bias in primary epithelial ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Gabriele Mittermeyer

    Full Text Available Although the expression of cell signaling proteins is used as prognostic and predictive biomarker, variability of protein levels within tumors is not well studied. We assessed intratumoral heterogeneity of protein expression within primary ovarian cancer. Full-length proteins were extracted from 88 formalin-fixed and paraffin-embedded tissue samples of 13 primary high-grade serous ovarian carcinomas with 5-9 samples each. In addition, 14 samples of normal fallopian tube epithelium served as reference. Quantitative reverse phase protein arrays were used to analyze the expression of 36 cell signaling proteins including HER2, EGFR, PI3K/Akt, and angiogenic pathways as well as 15 activated (phosphorylated proteins. We found considerable intratumoral heterogeneity in the expression of proteins with a mean coefficient of variation of 25% (range 17-53%. The extent of intratumoral heterogeneity differed between proteins (p<0.005. Interestingly, there were no significant differences in the extent of heterogeneity between phosphorylated and non-phosphorylated proteins. In comparison, we assessed the variation of protein levels amongst tumors from different patients, which revealed a similar mean coefficient of variation of 21% (range 12-48%. Based on hierarchical clustering, samples from the same patient clustered more closely together compared to samples from different patients. However, a clear separation of tumor versus normal tissue by clustering was only achieved when mean expression values of all individual samples per tumor were analyzed. While differential expression of some proteins was detected independently of the sampling method used, the majority of proteins only demonstrated differential expression when mean expression values of multiple samples per tumor were analyzed. Our data indicate that assessment of established and novel cell signaling proteins as diagnostic or prognostic markers may require sampling of serous ovarian cancers at

  5. Randomised study of systematic lymphadenectomy in patients with epithelial ovarian cancer macroscopically confined to the pelvis

    Science.gov (United States)

    Maggioni, A; Benedetti Panici, P; Dell'Anna, T; Landoni, F; Lissoni, A; Pellegrino, A; Rossi, R S; Chiari, S; Campagnutta, E; Greggi, S; Angioli, R; Manci, N; Calcagno, M; Scambia, G; Fossati, R; Floriani, I; Torri, V; Grassi, R; Mangioni, C

    2006-01-01

    No randomised trials have addressed the value of systematic aortic and pelvic lymphadenectomy (SL) in ovarian cancer macroscopically confined to the pelvis. This study was conducted to investigate the role of SL compared with lymph nodes sampling (CONTROL) in the management of early stage ovarian cancer. A total of 268 eligible patients with macroscopically intrapelvic ovarian carcinoma were randomised to SL (N=138) or CONTROL (N=130). The primary objective was to compare the proportion of patients with retroperitoneal nodal involvement between the two groups. Median operating time was longer and more patients required blood transfusions in the SL arm than the CONTROL arm (240 vs 150 min, P<0.001, and 36 vs 22%, P=0.012, respectively). More patients in the SL group had positive nodes at histologic examination than patients on CONTROL (9 vs 22%, P=0.007). Postoperative chemotherapy was delivered in 66% and 51% of patients with negative nodes on CONTROL and SL, respectively (P=0.03). At a median follow-up of 87.8 months, the adjusted risks for progression (hazard ratio [HR]=0.72, 95%CI=0.46–1.21, P=0.16) and death (HR=0.85, 95%CI=0.49–1.47, P=0.56) were lower, but not statistically significant, in the SL than the CONTROL arm. Five-year progression-free survival was 71.3 and 78.3% (difference=7.0%, 95% CI=–3.4–14.3%) and 5-year overall survival was 81.3 and 84.2% (difference=2.9%, 95% CI=−7.0–9.2%) respectively for CONTROL and SL. SL detects a higher proportion of patients with metastatic lymph nodes. This trial may have lacked power to exclude clinically important effects of SL on progression free and overall survival. PMID:16940979

  6. Ginsenoside 20(S-Rg3 targets HIF-1α to block hypoxia-induced epithelial-mesenchymal transition in ovarian cancer cells.

    Directory of Open Access Journals (Sweden)

    Ting Liu

    Full Text Available The prognosis of patients with ovarian cancer has remained poor mainly because of aggressive cancer progression. Since epithelial-mesenchymal transition (EMT is an important mechanism mediating invasion and metastasis of cancer cells, targeting the EMT process with more efficacious and less toxic compounds to inhibit metastasis is of great therapeutic value for the treatment of ovarian cancer. We have found for the first time that the ginsenoside 20(S-Rg3, a pharmacologically active component of the traditional Chinese herb Panax ginseng, potently blocks hypoxia-induced EMT of ovarian cancer cells in vitro and in vivo. Mechanistic studies confirm the mode of action of 20(S-Rg3, which reduces the expression of hypoxia-inducible factor 1α (HIF-1α by activating the ubiquitin-proteasome pathway to promote HIF-1α degradation. A decrease in HIF-1α in turn leads to up-regulation, via transcriptional suppression of Snail, of the epithelial cell-specific marker E-cadherin and down-regulation of the mesenchymal cell-specific marker vimentin under hypoxic conditions. Importantly, 20(S-Rg3 effectively inhibits EMT in nude mouse xenograft models of ovarian cancer, promising a novel therapeutic agent for anticancer therapy.

  7. BRAF Mutation Is Rare in Advanced-Stage Low-Grade Ovarian Serous Carcinomas

    Science.gov (United States)

    Wong, Kwong-Kwok; Tsang, Yvonne T.M.; Deavers, Michael T.; Mok, Samuel C.; Zu, Zhifei; Sun, Charlotte; Malpica, Anais; Wolf, Judith K.; Lu, Karen H.; Gershenson, David M.

    2010-01-01

    Low-grade ovarian serous carcinomas are believed to arise via an adenoma-serous borderline tumor-serous carcinoma sequence. In this study, we found that advanced-stage, low-grade ovarian serous carcinomas both with and without adjacent serous borderline tumor shared similar regions of loss of heterozygosity. We then analyzed 91 ovarian tumor samples for mutations in TP53, BRAF, and KRAS. TP53 mutations were not detected in any serous borderline tumors (n = 30) or low-grade serous carcinomas (n = 43) but were found in 73% of high-grade serous carcinomas (n = 18). BRAF (n = 9) or KRAS (n = 5) mutation was detected in 47% of serous borderline tumors, but among the low-grade serous carcinomas (39 stage III, 2 stage II, and 2 stage I), only one (2%) had a BRAF mutation and eight (19%) had a KRAS mutation. The low frequency of BRAF mutations in advanced-stage, low-grade serous carcinomas, which contrasts with previous findings, suggests that aggressive, low-grade serous carcinomas are more likely derived from serous borderline tumors without BRAF mutation. In addition, advanced-stage, low-grade carcinoma patients with BRAF or KRAS mutation have a better apparent clinical outcome. However, further investigation is needed. PMID:20802181

  8. Outcomes analysis of an alternative formulation of PEGylated liposomal doxorubicin in recurrent epithelial ovarian carcinoma during the drug shortage era

    Science.gov (United States)

    Berger, Jessica L; Smith, Ashlee; Zorn, Kristin K; Sukumvanich, Paniti; Olawaiye, Alexander B; Kelley, Joseph; Krivak, Thomas C

    2014-01-01

    Background In response to the critical shortage of Doxil®, the US Food and Drug Administration (FDA) allowed temporary importation of non-FDA-approved second-generation liposomal doxorubicin, Lipo-Dox®. Lipo-Dox utilizes a different liposomal particle than Doxil and demonstrates different pharmacokinetic properties. Its use has never been evaluated in a North American population. The objective of this study was to evaluate the efficacy and tolerability of Lipo-Dox at Magee-Womens Hospital, University of Pittsburgh Medical Center, for patients with recurrent epithelial ovarian cancer who were treated during the Doxil shortage. Methods Patients treated with Lipo-Dox from January 2012 to December 2012 were identified retrospectively. Disease response was defined radiographically by RECIST (Response Evaluation Criteria in Solid Tumors) or biochemically by CA-125 level if measurable disease was not present. Survival was defined from the start date of Lipo-Dox until the date of progression or death. Toxicity was assessed by the Gynecologic Oncology Group common toxicity criteria. Results Eighteen patients with recurrent epithelial ovarian cancer who received Lipo-Dox were identified. These patients had a median of three prior treatment regimens. The median number of Lipo-Dox cycles given was 3.5 (range 1–8). No patients had a complete or partial response. Two patients had stable disease over a mean follow-up of 144.5 days. Fourteen patients had progressive disease, with a median time to progression of 82 days. Progression was based on CA-125 in four patients and RECIST in the remainder. Nine patients died from the disease. Conclusion Although this represents a small, pretreated population, there were no clinical responses to Lipo-Dox, raising the question as to whether it is an equivalent substitute for Doxil. Further evaluation is needed, but if confirmed, these findings raise concerns regarding the use of current stocks of Lipo-Dox, as well as the prudence of

  9. The role of KRAS rs61764370 in invasive epithelial ovarian cancer: implications for clinical testing

    DEFF Research Database (Denmark)

    Pharoah, Paul D P; Palmieri, Rachel T; Ramus, Susan J

    2011-01-01

    PURPOSE: An assay for the single nucleotide polymorphism (SNP) rs61764370 has recently been commercially marketed as a clinical test to aid ovarian cancer risk evaluation in women with family histories of the disease. rs67164370 is in a 3'UTR miRNA binding site of the KRAS oncogene, and is a cand......PURPOSE: An assay for the single nucleotide polymorphism (SNP) rs61764370 has recently been commercially marketed as a clinical test to aid ovarian cancer risk evaluation in women with family histories of the disease. rs67164370 is in a 3'UTR miRNA binding site of the KRAS oncogene...... studies with all-cause mortality data.RESULTS: No evidence of association was observed between genotype and risk of unselected EOC (odds ratio (OR)=1.02, 95% confidence interval (CI)=0.95-1.10), serous EOC (OR=1.08, 95%CI=0.98-1.18), familial EOC (OR=1.09, 95%CI=0.78-1.54), or among women carrying...

  10. Clinical Progress of Treatment on Recurrent Epithelial Ovarian Cancer%复发性上皮性卵巢癌临床治疗进展

    Institute of Scientific and Technical Information of China (English)

    党彩玲

    2012-01-01

    Most of patients with epithelial ovarian cancer was advanced as the initial treatment. Although cytoreductive surgery and adjuvant paclitaxel/platinum-based chemotherapy have made the most of patients in clinical remission,but there are still 80% of patients to relapse eventually. The principle of treatment for recurrent EOC is palliative rather than cure. The quality of life should be to consider once again on treatment. According to the situation in patients with initial surgery and postoperative chemotherapy and means,efficacy,toxicity,relapse types,the treatment programs was to be developed individually in order to alleviate and control symptoms of the disease,and improve quality of life and prolong progression-free survival for patient. As only a single lesion or recurrence lesion reduction by surgery effectively,the cytoreductive surgery combined with chemotherapy would be to implement. While those with large and extensive metastasis even,the only chemotherapy would be to consider. In developing the program of chemotherapy,drug-resistant,refractory and refractory patients was often considered as a group,which would be to encourage to ongoing clinical trials or receiving non-platinum chemotherapy,the patients with sensitive ovarian cancer was recommended to receive platinum or platinum plus paclitaxel-based chemotherapy. Biological treatment as an alternative cancer therapy model was more and more attended as an importance strong complement to traditional surgery and chemotherapy.%上皮性卵巢癌(epithelial ovarian cancer,EOC)患者如初次就诊时已为晚期,虽然肿瘤细胞减灭术和术后辅以紫杉醇/铂类为基础的联合化疗可使大部分患者获得临床缓解,但最终仍有80%的患者复发.复发性EOC 的治疗原则是姑息而不是治愈,生存质量是再次治疗时考虑的重要因素.可根据患者初次手术情况及术后化疗方案及途径、疗效、毒副反应、复发类型等制定个体化的治疗方

  11. The expression and significance of Stathmin in epithelial ovarian cancer%Stathmin在上皮性卵巢癌组织中的表达及意义

    Institute of Scientific and Technical Information of China (English)

    石英; 翁艳洁; 周文娟; 周婷; 陈刚; 王常玉

    2011-01-01

    背景与目的:Stathmin是一种重要的微管调节蛋白,参与多种肿瘤的发生、发展.本研究旨在验证并探讨Stathmin在上皮性卵巢癌中的表达及意义.方法:利用免疫组化和逆转录聚合酶链反应(RT-PCR)方法检测22例卵巢正常上皮组织,16例良性肿瘤和50例上皮性卵巢癌组织中Stathmin的表达.结果:上皮性卵巢癌中Stathmin mRNA的表达明显高于卵巢良性肿瘤(PO.05).进一步利用x2检验统计分析得出,Stathmin蛋白与卵巢癌的临床分期、病理分级、淋巴转移相关(P0.05).结论:Stathmin在上皮性卵巢癌中高表达,可能与卵巢癌的发生、发展相关.%Background and purpose: Stathmin is identified as a kind of important microtubules regulatory protein and participates in multiple tumorigenesis. In this study, we investigated the expression and significance of Stathmin in epithelial ovarian cancer. Methods: The expression levels of Stathmin in 22 cases of normal ovarian tissues, 16 cases of benign ovarian tumors and 50 cases of epithelial ovarian cancers were examined by RT-PCR and immunohistochemical staining. Results: The Stathmin mRNA expression in ovarian epithelial cancer was higher than that in normal and benign tumor tissues(P0.05). Χ2 analysis was utilized to show that the expression of Stathmin was related to clinical stages, histological grade and lymph node metastasis (P0.05). Conclusion-. Stathmin overexpression may correlate with the occurrence and progression of epithelial ovarian cancer.

  12. Regulatory Effect of E2, IL-6 and IL-8 on the Growth of Epithelial Ovarian Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    Yue Wang; Jie Yang; Yan Gao; Yongrui Du; Leyuan Bao; Wenyan Niu; Zhi Yao

    2005-01-01

    To determine the regulatory effects of estrogen and cytokine IL-6 and IL-8 on the growth of epithelial ovarian cancer (OVCA), we first examined the status of estrogen receptors (ERα and ERβ), IL-6 receptor (IL-6Rα and gp130), and IL-8 receptor (IL-8RA and IL-8RB) on five epithelial OVCA cell lines by semiquantitative RT-PCR and Western blot analysis. Results showed that the expressions of these receptors were variable on the five cells.Those OVCA cells expressing the receptors were selected to study related molecular mechanism. MTT assay was performed to observe the effects of 17β-estradiol (E2), IL-6 and IL-8 on cell proliferation. We discovered that E2 markedly promoted the proliferation of CAOV-3 and OVCAR-3 cell in a time- and dose-dependent manner.Tamoxifen (Txf), an ER inhibitor, completely blocked the proliferation of the E2-induced cells, and IL-6- or/and IL-8-neutralizing antibody only showed partially blocking activity. IL-6 and IL-8 were able to significantly stimulate CAOV-3 and OVCAR-3 cell proliferation in a time- and dose-dependent manner, which had a potential synergistic effect on CAOV-3 cells but not on OVCAR-3 cells. The cell proliferation induced by these two cytokines was abolished completely by their specific neutralizing antibodies, partially by Txf, but not by unrelated goat IgG.Taken together, our results suggested that estrogen, IL-6 and IL-8 could modulate OVCA growth by forming a reciprocal cascade with amplifying effect. Cellular & Molecular Immunology.

  13. Severe prolonged gastroparesis after cytoreductive surgery in an advanced ovarian cancer patient.

    Science.gov (United States)

    Caprino, P; Fagotti, A; Missere, M; Fanfani, F; Scambia, G

    2006-01-01

    Number and type of complications after ovarian cancer surgery can vary greatly according to both the patient's characteristics, and the extension and type of surgery. Current literature lacks in mentioning specific gastrointestinal side effects, which could be evidenced during the early postoperative course of patients submitted to major gynecological oncologic surgery. A severe gastroparesis prolonged for 2 months after cytoreductive surgery in an advanced ovarian cancer patient was successfully treated with conservative multidrug therapy. Gastroparesis has to be enumerated as a rare but possible event after major gynecological oncologic surgery. A conservative management involving decompressive nasogastric tube, nutritional support, antiemetic drugs, prokinetic drugs is suggested, while surgical therapy is only recommended in a very small subset of unmanageable patients.

  14. The clinical significance of the expression of the metastasis suppressor gene KAI1 in epithelial ovarian carcinoma

    Institute of Scientific and Technical Information of China (English)

    Zhang Xiangning; Han Qiuyu; Li Xiaocui

    2005-01-01

    Objective:To investigate the potential role of KAI1 in epithelial ovarian carcinoma(EOC), and to determine whether the expression of the KAI1 gene is associated with EOC progression.The clinical significance in this tumor is also evaluated.Method: Immunohistochemistry SP method was performed to examine the expression level of KAI1 in EOC.Results: Thirty eight of 66 cancer specimens showed KAI1 protein positive (57.58%),which lower significantly than that in the patients with benign and borderline tumors(90.91%).The statistical evaluation showed that the expression of KAI1 had a correlation with FIGO stags as well as lymph node metastasis(or distant metastasis)(P<0.05).It also revealed an inverse relationship between histological grade and KAI1 expression (P<0.05).Conclusion: KAI1 protein expression is closely correlated with the malignent progression and metastasis of EOC; detecting the expression of KAI1 probably possesses clinical significance in evaluating the differentiation,tumor progression and predicting the prognosis of EOC.

  15. Intensive cisplatin/oral etoposide for epithelial ovarian cancer: the Cambridge Gynae-Oncology Centre experience: too toxic for relapse?

    Science.gov (United States)

    Gounaris, Ioannis; Iddawela, Mahesh; Parkinson, Christine; Pratt, Jennie; Hatcher, Helen; Basu, Bristi; Tan, Li Tee; Brenton, James D; Earl, Helena M

    2016-03-01

    Intensive cisplatin and oral etoposide for relapsed epithelial ovarian cancer (EOC), commonly known as the van der Burg (VDB) protocol, has been reported to improve response rates and progression-free survival. We report on all patients with relapsed EOC treated on the VDB protocol at the Cambridge Gynae-Oncology Centre. From the institutional databases, we identified all patients treated since 2001. We extracted demographic, clinical, treatment, and toxicity data and outcomes. We used Cox regression to identify predictors of survival. A total of 35 patients were treated on the VDB protocol. Toxicity was significant, with grade 3/4 fatigue, nausea and vomiting affecting 46, 46 and 29% of patients, respectively. Six patients had grade 3/4 infection and four (11%) deaths occurred on treatment. Efficacy was encouraging, with a radiological response rate of 43%, a median progression-free survival of 5.8 months and a median overall survival of 14.1 months. No significant difference in efficacy was seen between platinum-resistant and sensitive patients. We report significant activity of the VDB protocol in a routine clinical setting. However, the high rates of serious toxicity and treatment-related deaths among patients treated with palliative intent proved unacceptable. The Cambridge Gynae-Oncology Centre no longer uses this regimen in women with relapsed EOC.

  16. The use of laser microdissection in the identification of suitable reference genes for normalization of quantitative real-time PCR in human FFPE epithelial ovarian tissue samples.

    Directory of Open Access Journals (Sweden)

    Jing Cai

    Full Text Available Quantitative real-time PCR (qPCR is a powerful and reproducible method of gene expression analysis in which expression levels are quantified by normalization against reference genes. Therefore, to investigate the potential biomarkers and therapeutic targets for epithelial ovarian cancer by qPCR, it is critical to identify stable reference genes. In this study, twelve housekeeping genes (ACTB, GAPDH, 18S rRNA, GUSB, PPIA, PBGD, PUM1, TBP, HRPT1, RPLP0, RPL13A, and B2M were analyzed in 50 ovarian samples from normal, benign, borderline, and malignant tissues. For reliable results, laser microdissection (LMD, an effective technique used to prepare homogeneous starting material, was utilized to precisely excise target tissues or cells. One-way analysis of variance (ANOVA and nonparametric (Kruskal-Wallis tests were used to compare the expression differences. NormFinder and geNorm software were employed to further validate the suitability and stability of the candidate genes. Results showed that epithelial cells occupied a small percentage of the normal ovary indeed. The expression of ACTB, PPIA, RPL13A, RPLP0, and TBP were stable independent of the disease progression. In addition, NormFinder and geNorm identified the most stable combination (ACTB, PPIA, RPLP0, and TBP and the relatively unstable reference gene GAPDH from the twelve commonly used housekeeping genes. Our results highlight the use of homogeneous ovarian tissues and multiple-reference normalization strategy, e.g. the combination of ACTB, PPIA, RPLP0, and TBP, for qPCR in epithelial ovarian tissues, whereas GAPDH, the most commonly used reference gene, is not recommended, especially as a single reference gene.

  17. The use of laser microdissection in the identification of suitable reference genes for normalization of quantitative real-time PCR in human FFPE epithelial ovarian tissue samples.

    Science.gov (United States)

    Cai, Jing; Li, Tao; Huang, Bangxing; Cheng, Henghui; Ding, Hui; Dong, Weihong; Xiao, Man; Liu, Ling; Wang, Zehua

    2014-01-01

    Quantitative real-time PCR (qPCR) is a powerful and reproducible method of gene expression analysis in which expression levels are quantified by normalization against reference genes. Therefore, to investigate the potential biomarkers and therapeutic targets for epithelial ovarian cancer by qPCR, it is critical to identify stable reference genes. In this study, twelve housekeeping genes (ACTB, GAPDH, 18S rRNA, GUSB, PPIA, PBGD, PUM1, TBP, HRPT1, RPLP0, RPL13A, and B2M) were analyzed in 50 ovarian samples from normal, benign, borderline, and malignant tissues. For reliable results, laser microdissection (LMD), an effective technique used to prepare homogeneous starting material, was utilized to precisely excise target tissues or cells. One-way analysis of variance (ANOVA) and nonparametric (Kruskal-Wallis) tests were used to compare the expression differences. NormFinder and geNorm software were employed to further validate the suitability and stability of the candidate genes. Results showed that epithelial cells occupied a small percentage of the normal ovary indeed. The expression of ACTB, PPIA, RPL13A, RPLP0, and TBP were stable independent of the disease progression. In addition, NormFinder and geNorm identified the most stable combination (ACTB, PPIA, RPLP0, and TBP) and the relatively unstable reference gene GAPDH from the twelve commonly used housekeeping genes. Our results highlight the use of homogeneous ovarian tissues and multiple-reference normalization strategy, e.g. the combination of ACTB, PPIA, RPLP0, and TBP, for qPCR in epithelial ovarian tissues, whereas GAPDH, the most commonly used reference gene, is not recommended, especially as a single reference gene.

  18. Ruptured ovarian cystic teratoma in pregnancy with diffuse peritoneal reaction mimicking advanced ovarian malignancy: a case report

    Directory of Open Access Journals (Sweden)

    Maiti Sachchidananda

    2008-06-01

    Full Text Available Abstract Introduction This case illustrates the unusual complication of granulomatous peritonitis following rupture of a dermoid cyst in pregnancy resembling disseminated ovarian carcinoma. To the best of the authors' knowledge, this is the first report of this complication during advanced pregnancy in the literature. Case presentation A dermoid cyst ruptured during surgical removal in the second trimester of pregnancy in a 27-year-old primigravida. Postoperatively the patient suffered pulmonary embolism and leakage of sebaceous material through the abdominal wound. She gradually developed significant abdominal distension, gastrointestinal symptoms and lost more than 8 kg of weight in the 12 weeks postoperatively. The baby was delivered at 31 weeks by a technically challenging caesarean section owing to severe dense adhesions obscuring the uterus. Bowel resection was performed for suspected malignant infiltration and adhesion causing obstruction. She had a protracted convalescence with an ileostomy and mucus fistula. Histology confirmed granulation without malignancy. One year following the surgical treatment, she had recovered well and was planning her next pregnancy. Conclusion Although granulomatous peritonitis following rupture of a dermoid cyst is very rare, awareness is the key to diagnosis and appropriate management. Per-operative frozen section may be helpful.

  19. What Is Ovarian Cancer?

    Science.gov (United States)

    ... based on how much it looks like normal tissue on a scale of 1, 2, or 3. Grade 1 epithelial ovarian carcinomas look more like normal tissue and tend to have a better prognosis (outlook). Grade 3 epithelial ovarian carcinomas look less like normal tissue and ...

  20. 上皮性卵巢癌中HOST2 lncRNA的表达及临床意义%Expression of HOST2 lncRNA in Ovarian Epithelial Carcinoma and Its Clinical Significance

    Institute of Scientific and Technical Information of China (English)

    刘静; 彭萍; 汪先桃

    2015-01-01

    Objective:To detect the expression of HOST2 lncRNA in epithelial ovarian carcinoma, and analyze its clinical significance.Method:The HOST2 expression of epithelial ovarian cancer , epithelial borderline tumor and epithelial ovarian normal tissues were detected by the PCR method. Clinical significance differences in the expression of HOST2 lncRNA in different ovarian tissue was analyzed.Result:Expression of epithelial ovarian cancer tissue and epithelial borderline tumor was obviously higher than expression of epithelial normal ovarian tissues,there was significant statistical difference (P0.05).HOST2 lncRNA’s expression of different clinical stages of epithelial ovarian tumor was no significant difference(P>0.05).Conclusion:HOST2 lncRNA expression in ovarian cancer and epithelial borderline tumor, maybe a marker for early diagnosis of ovarian cancer.%目的:检测HOST2 lncRNA在上皮性卵巢组织的表达水平,并分析其临床意义。方法:利用实时荧光定量PCR方法检测HOST2 lncRNA在上皮性卵巢癌、上皮性交界性瘤和上皮性正常卵巢组织的表达水平,分析HOST2 lncRNA在不同上皮性卵巢组织表达差异的临床意义。结果:HOST2 lncRNA在上皮性卵巢癌组织和上皮性交界性瘤表达量明显高于上皮性正常卵巢组织的表达,差异均有统计学意义(P0.05)。HOST2 lncRNA在不同临床分期的上皮性卵巢癌中表达量无明显差异(P>0.05)。结论:在上皮性卵巢癌和交界性卵巢瘤中HOST2 lncRNA均有表达,可作为上皮性卵巢癌早期诊断的一个分子诊断标志物。

  1. Re-epithelialization: advancing epithelium frontier during wound healing.

    Science.gov (United States)

    Ben Amar, M; Wu, M

    2014-04-06

    The first function of the skin is to serve as a protective barrier against the environment. Its loss of integrity as a result of injury or illness may lead to a major disability and the first goal of healing is wound closure involving many biological processes for repair and tissue regeneration. In vivo wound healing has four phases, one of them being the migration of the healthy epithelium surrounding the wound in the direction of the injury in order to cover it. Here, we present a theoretical model of the re-epithelialization phase driven by chemotaxis for a circular wound. This model takes into account the diffusion of chemoattractants both in the wound and the neighbouring tissue, the uptake of these molecules by the surface receptors of epithelial cells, the migration of the neighbour epithelium, the tension and proliferation at the wound border. Using a simple Darcy's law for cell migration transforms our biological model into a free-boundary problem, which is analysed in the simplified circular geometry leading to explicit solutions for the closure and making stability analysis possible. It turns out that for realistic wound sizes of the order of centimetres and from experimental data, the re-epithelialization is always an unstable process and the perfect circle cannot be observed, a result confirmed by fully nonlinear simulations and in agreement with experimental observations.

  2. Pathobiology of ovarian carcinomas

    Institute of Scientific and Technical Information of China (English)

    Mojgan Devouassoux-Shisheboran; Catherine Genestie

    2015-01-01

    Ovarian tumors comprise a heterogeneous group of lesions, displaying distinct tumor pathology and oncogenic potentiel. These tumors are subdivided into three main categories: epithelial, germ cell, and sex-cord stromal tumors. We report herein the newly described molecular abnormalities in epithelial ovarian cancers (carcinomas). Immunohistochemistry and molecular testing help pathologists to decipher the significant heterogeneity of this disease. Our better understanding of the molecular basis of ovarian carcinomas represents the first step in the development of targeted therapies in the near future.

  3. Advances in Tumor Screening, Imaging, and Avatar Technologies for High-Grade Serous Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Anders eOhman

    2014-11-01

    Full Text Available The majority of high-grade serous ovarian carcinoma cases are detected in advanced stages when treatment options are limited. Surgery is less effective at eradicating the disease when it is widespread, resulting in high rates of disease relapse and chemoresistance. Current screening techniques are ineffective for early tumor detection and consequently, BRCA mutations carriers, with an increased risk for developing high-grade serous ovarian cancer, elect to undergo risk-reducing surgery. While prophylactic surgery is associated with a significant reduction in the risk of cancer development, it also results in surgical menopause and significant adverse side effects. The development of efficient early-stage screening protocols and imaging technologies is critical to improving the outcome and quality of life for current patients and women at increased risk. In addition, more accurate animal models are necessary in order to provide relevant in vivo testing systems and advance our understanding of the disease origin and progression. Moreover, both genetically engineered and tumor xenograft animal models enable the preclinical testing of novel imaging techniques and molecularly targeted therapies as they become available. Recent advances in xenograft technologies have made possible the creation of avatar mice, personalized tumorgrafts, which can be used as therapy testing surrogates for individual patients prior to or during treatment. High-grade serous ovarian cancer may be an ideal candidate for use with avatar models based on key characteristics of the tumorgraft platform. This review explores multiple strategies, including novel imaging and screening technologies in both patients and animal models, aimed at detecting cancer in the early stages and improving the disease prognosis.

  4. Expression and significance of GATA3 in epithelial ovarian cancer%GATA3在上皮性卵巢癌中的表达及其意义

    Institute of Scientific and Technical Information of China (English)

    马杰; 赵卫东; 邹强; 金夏; 张丽娜; 曹振平; 冯定庆

    2011-01-01

    目的:探讨GATA3在上皮性卵巢癌组织中的表达及其意义.方法:应用RT-PCR和Western Blotting检测30例上皮性卵巢癌标本和18例正常卵巢组织中GATA3 mRNA及蛋白水平表达情况,应用免疫组化检测肿瘤组织和正常卵巢组织中GATA3蛋白定位及表达情况.结果:RT-PCR提示上皮性卵巢癌组织中GATA3 mRNA表达升高,在卵巢癌组织和正常卵巢组织中的阳性表达率分别为90.0%和44.4%,差异有统计学意义(P<0.05);Western Blotting和免疫组化提示卵巢癌组织中GATA3在蛋白水平的表达明显降低,正常卵巢组织中定位在细胞核内,而卵巢癌组织中细胞核内表达不明显.结论:卵巢癌组织中GATA3在基因水平表达较正常卵巢组织上调,其翻译的蛋白表达却降低,可能是GATA3 mRNA合成的蛋白大多由核内转移而出,从而促进肿瘤的发生与发展,为进一步探讨上皮性卵巢癌的发病机理提供了实验依据.%Objective: To explore the expression and significance of GATA3 in epithelial ovarian cancer tissue. Methods; RT -PCR and Western Blotting were used to detect the expression levels of GATA3 mRNA and protein in 30 cases with epithelial ovarian cancer and 18 cases with normal ovarian tissue, immunohistoehemical method was used to detect the locations and expressions of GATA3 protein in epithelial ovarian cancer tissue and normal ovarian tissue. Results: The result of RT - PCR showed that the expression level of GAT A3 mRNA in epithelial ovarian cancer tissue increased, the positive expression rates of GATA3 mRNA in epithelial ovarian cancer tissue and normal ovarian tissue were 90. 0% and 44. 4% , respectively, there was significant difference between the two groups (P < 0. 05 ) ; the results of Western Blotting and immunohistoehemical method indicated that the expression level of GAT A3 protein in epithelial ovarian cancer tissue decreased significantly, GAT A3 protein located in cell nucleus of normal ovarian tissue

  5. Dietary intake of acrylamide and epithelial ovarian cancer risk in the european prospective investigation into cancer and nutrition (EPIC) cohort.

    Science.gov (United States)

    Obón-Santacana, Mireia; Peeters, Petra H M; Freisling, Heinz; Dossus, Laure; Clavel-Chapelon, Françoise; Baglietto, Laura; Schock, Helena; Fortner, Renée T; Boeing, Heiner; Tjønneland, Anne; Olsen, Anja; Overvad, Kim; Menéndez, Virginia; Sanchez, Maria-José; Larrañaga, Nerea; Huerta Castaño, José María; Barricarte, Aurelio; Khaw, Kay-Tee; Wareham, Nick; Travis, Ruth C; Merritt, Melissa A; Trichopoulou, Antonia; Trichopoulos, Dimitrios; Orfanos, Philippos; Masala, Giovanna; Sieri, Sabina; Tumino, Rosario; Vineis, Paolo; Mattiello, Amalia; Bueno-de-Mesquita, H B; Onland-Moret, N Charlotte; Wirfält, Elisabeth; Stocks, Tanja; Idahl, Annika; Lundin, Eva; Skeie, Guri; Gram, Inger T; Weiderpass, Elisabete; Riboli, Elio; Duell, Eric J

    2015-01-01

    Acrylamide, classified in 1994 by the International Agency for Research on Cancer (IARC) as "probably carcinogenic" to humans, was discovered in 2002 in some heat-treated, carbohydrate-rich foods. The association between dietary acrylamide intake and epithelial ovarian cancer risk (EOC) has been previously studied in one case-control and three prospective cohort studies which obtained inconsistent results and could not further examine histologic subtypes other than serous EOC. The present study was carried out in the European Prospective Investigation into Cancer and Nutrition (EPIC) subcohort of women (n = 325,006). Multivariate Cox proportional hazards models were used to assess the association between questionnaire-based acrylamide intake and EOC risk. Acrylamide was energy-adjusted using the residual method and was evaluated both as a continuous variable (per 10 μg/d) and in quintiles; when subgroups by histologic EOC subtypes were analyzed, acrylamide intake was evaluated in quartiles. During a mean follow-up of 11 years, 1,191 incident EOC cases were diagnosed. At baseline, the median acrylamide intake in EPIC was 21.3 μg/d. No associations and no evidence for a dose-response were observed between energy-adjusted acrylamide intake and EOC risk (HR10μg/d,1.02; 95% CI, 0.96-1.09; HRQ5vsQ1, 0.97; 95% CI, 0.76-1.23). No differences were seen when invasive EOC subtypes (582 serous, 118 endometrioid, and 79 mucinous tumors) were analyzed separately. This study did not provide evidence that acrylamide intake, based on food intake questionnaires, was associated with risk for EOC in EPIC. Additional studies with more reliable estimates of exposure based on biomarkers may be needed.

  6. Expression of preoperative KISS1 gene in tumor tissue with epithelial ovarian cancer and its prognostic value.

    Science.gov (United States)

    Cao, Fang; Chen, Liping; Liu, Manhua; Lin, Weiwei; Ji, Jinlong; You, Jun; Qiao, Fenghai; Liu, Hongbin

    2016-11-01

    Our study aimed to elucidate the role of Kisspeptin (KISS1) in tumor tissues of patients with epithelial ovarian cancer (EOC) and investigate the prognostic value of this biomarker.Forty EOC patients and 20 uterine fibroids female patients with healthy ovaries undergoing cytoreductive surgery between January 2010 and January 2014 in our hospital were enrolled in this study. KISS1 expression in tumor and normal tissues was detected. Correlations between clinic-pathologic variables and KISS1 expression in EOC tissues and the prognostic value of KISS1 for overall survival were evaluated.During the follow-up of 11.2 to 62.1 months, the overall survival rate and mean survival time were 28.9% (11/38) and 38.35 ± 2.84 months. Preoperative KISS1 mRNA was higher in tumor tissue than in normal tissue (P <0.001), and it was associated with histologic grade of tumor, surgical FIGO stage, metastasis, and residual tumor size (all P <0.05). Multivariate survival analysis indicated significant influence of residual tumor size (HR = 2.357, P = 0.039) and preoperative KISS1 mRNA (HR = 0.0001, P <0.001) on mean survival time. Patients with low KISS1 mRNA expression had shorter survival time than those with high expression (P = 0.001).Preoperative KISS1 mRNA was a potential prognostic biomarker for EOC, and high preoperative KISS1 expression indicated a favorable prognosis.

  7. Sulforaphane induces cell cycle arrest by protecting RB-E2F-1 complex in epithelial ovarian cancer cells

    Directory of Open Access Journals (Sweden)

    Morris Robert

    2010-03-01

    Full Text Available Abstract Background Sulforaphane (SFN, an isothiocyanate phytochemical present predominantly in cruciferous vegetables such as brussels sprout and broccoli, is considered a promising chemo-preventive agent against cancer. In-vitro exposure to SFN appears to result in the induction of apoptosis and cell-cycle arrest in a variety of tumor types. However, the molecular mechanisms leading to the inhibition of cell cycle progression by SFN are poorly understood in epithelial ovarian cancer cells (EOC. The aim of this study is to understand the signaling mechanisms through which SFN influences the cell growth and proliferation in EOC. Results SFN at concentrations of 5 - 20 μM induced a dose-dependent suppression of growth in cell lines MDAH 2774 and SkOV-3 with an IC50 of ~8 μM after a 3 day exposure. Combination treatment with chemotherapeutic agent, paclitaxel, resulted in additive growth suppression. SFN at ~8 μM decreased growth by 40% and 20% on day 1 in MDAH 2774 and SkOV-3, respectively. Cells treated with cytotoxic concentrations of SFN have reduced cell migration and increased apoptotic cell death via an increase in Bak/Bcl-2 ratio and cleavage of procaspase-9 and poly (ADP-ribose-polymerase (PARP. Gene expression profile analysis of cell cycle regulated proteins demonstrated increased levels of tumor suppressor retinoblastoma protein (RB and decreased levels of E2F-1 transcription factor. SFN treatment resulted in G1 cell cycle arrest through down modulation of RB phosphorylation and by protecting the RB-E2F-1 complex. Conclusions SFN induces growth arrest and apoptosis in EOC cells. Inhibition of retinoblastoma (RB phosphorylation and reduction in levels of free E2F-1 appear to play an important role in EOC growth arrest.

  8. Ovarian Cancer Stroma: Pathophysiology and the Roles in Cancer Development

    Energy Technology Data Exchange (ETDEWEB)

    Furuya, Mitsuko [Department of Pathology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004 (Japan)

    2012-07-18

    Ovarian cancer represents one of the cancers with the worst prognostic in adult women. More than half of the patients who present with clinical signs such as abdominal bloating and a feeling of fullness already show advanced stages. The majority of ovarian cancers grow as cystic masses, and cancer cells easily spread into the pelvic cavity once the cysts rupture or leak. When the ovarian cancer cells disseminate into the peritoneal cavity, metastatic nests may grow in the cul-de-sac, and in more advanced stages, the peritoneal surfaces of the upper abdomen become the next largest soil for cancer progression. Ascites is also produced frequently in ovarian cancers, which facilitates distant metastasis. Clinicopathologic, epidemiologic and molecular studies on ovarian cancers have improved our understanding and therapeutic approaches, but still further efforts are required to reduce the risks in the patients who are predisposed to this lethal disease and the mortality of the patients in advanced stages. Among various molecules involved in ovarian carcinogenesis, special genes such as TP53, BRCA1 and BRCA2 have been well investigated. These genes are widely accepted as the predisposing factors that trigger malignant transformation of the epithelial cells of the ovary. In addition, adnexal inflammatory conditions such as chronic salpingitis and ovarian endometriosis have been great research interests in the context of carcinogenic background of ovarian cancers. In this review, I discuss the roles of stromal cells and inflammatory factors in the carcinogenesis and progression of ovarian cancers.

  9. Utility of Serum miR-125b as a Diagnostic and Prognostic Indicator and Its Alliance with a Panel of Tumor Suppressor Genes in Epithelial Ovarian Cancer.

    Science.gov (United States)

    Zuberi, Mariyam; Khan, Imran; Mir, Rashid; Gandhi, Gauri; Ray, Prakash Chandra; Saxena, Alpana

    2016-01-01

    MicroRNAs (miRNAs) have been found to be dysregulated in epithelial ovarian cancer (EOC) and may function as either tumor suppressor genes (TSGs) or as oncogenes. Hypermethylation of miRNA silences the tumour suppressive function of a miRNA or hypermethylation of a TSG regulating that miRNA (or vice versa) leads to its loss of function. The present study aims to evaluate the impact of aberrant microRNA-125b (miR-125b) expression on various clinicopathological features in epithelial ovarian cancer and its association with anomalous methylation of several TSGs. We enrolled 70 newly diagnosed cases of epithelial ovarian cancer, recorded their clinical history and 70 healthy female volunteers. Serum miR-125b levels were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and the methylation status of various TSGs was investigated by methylation specific PCR. ROC curves were constructed to estimate the diagnostic and prognostic usefulness of miR-125b. The Kaplan-Meier method was applied to compare survival curves. Expression of miR-125b was found to be significantly upregulated (pmiR-125b was found to be significantly associated with FIGO stage, lymph node and distant metastasis. ROC curve for diagnostic potential yielded significant AUC with an equitable sensitivity and specificity. ROC curves for prognosis yielded significant AUCs for histological grade, distal metastasis, lymph node status and survival. The expression of miR-125b also correlated significantly with the hypermethylation of TSGs. Our results indicate that DNA hypermethylation may be involved in the inactivation of miR-125b and miR-125b may function as a potential independent biomarker for clinical outcome in EOC.

  10. The role of metabolic tumor volume and total lesion glycolysis on {sup 18}F-FDG PET/CT in the prognosis of epithelial ovarian cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jeong Won; Cho, Arthur; Lee, Jae-Hoon; Yun, Mijin; Lee, Jong Doo; Kang, Won Jun [Yonsei University College of Medicine, Department of Nuclear Medicine, 134 Shinchon-dong, Seodaemoon-gu, Seoul (Korea, Republic of); Kim, Young Tae [Yonsei University College of Medicine, Department of Obstetrics and Gynecology, 134 Shinchon-dong, Seodaemoon-gu, Seoul (Korea, Republic of)

    2014-10-15

    This study assessed the prognostic value of pre-operative 2-[{sup 18}F] fluoro-2-deoxy-D-glucose ({sup 18}F-FDG) positron emission tomography/computed tomography (PET/CT) volumetric parameters, including metabolic tumor volume (MTV) and total lesion glycolysis (TLG), in patients with epithelial ovarian cancer. A total of 175 patients with epithelial ovarian cancer who underwent {sup 18} F-FDG PET/CT and subsequent cytoreductive surgery were retrospectively enrolled. Maximum standardized uptake value (SUVmax) on {sup 18}F-FDG PET/CT was measured for all patients. Because nine patients showed low tumor-to-background uptake ratios, MTV and TLG were measured in 166 patients. Univariate and multivariate analyses were performed to evaluate the prognostic significance of SUVmax, MTV, TLG, and clinicopathological factors for disease progression-free survival. Disease progressed in 78 (44.6 %) of the 175 patients, and the 2-year disease progression-free survival rate was 57.5 %. Univariate analysis showed that tumor stage, histopathological type, presence of regional lymph node metastasis, residual tumor after cytoreductive surgery, pre-operative serum carbohydrate antigen 125 (CA125) level, SUVmax, MTV, and TLG were significant prognostic factors (p < 0.05). Among these variables, tumor stage (p = 0.0006) and TLG (p = 0.008) independently correlated with disease progression-free survival on multivariate analysis. The disease progression rate was only 2.3 % in stage I-II patients with low TLG (≤100.0), compared to 80.0 % in stage III-IV patients with high TLG (>100.0). Along with tumor stage, TLG is an independent prognostic factor for disease progression after cytoreductive surgery in patients with epithelial ovarian cancer. By combining tumor stage and TLG, one can further stratify the risk of disease progression for patients undergoing cytoreductive surgery. (orig.)

  11. Panitumumab and pegylated liposomal doxorubicin to platinum-resistant epithelial ovarian cancer with KRAS wild-type: An ongoing, nonrandomized, multicenter, phase II trial

    DEFF Research Database (Denmark)

    Dahl Steffensen, Karina; Waldstrøm, Marianne; Lund, B

    2010-01-01

    , and head and neck cancer. No previous studies have evaluated the effect of panitumumab in OC based on KRAS mutation status. Methods: Eligibility criteria are confirmed stage I-IV primary epithelial ovarian/fallopian/peritoneal cancer patients with progression either during or within 6 months after end...... to a total of 33 patients. At present, 15 patients have been enrolled. The primary endpoint is to investigate the response rate in platinum-resistant, KRAS wild- type OC patients treated with PLD supplemented with panitumumab. Translational research is included as a secondary endpoint and tumor tissue...

  12. The integration of anthracyclines in the treatment of advanced ovarian cancer.

    Science.gov (United States)

    Lück, H J; Du Bois, A; Weber, B; Pfisterer, J; Goupil, A; Kuhn, W; Barats, J C; Blohmer, J; Mousseau, M; Schröder, W; Meier, W; Möbus, V; Richter, B

    2001-01-01

    Since the publication of the Gynecologic Oncology Group (GOG) protocol 111 in 1996, and the results of the Arbeitgemeinschaft Gyna kologische Onkologie (AGO) trial Ovar-3 and the GOG protocol 158, the combination of platinum and paclitaxel has been adopted as the standard therapy in advanced ovarian cancer. One option for achieving further progress in the first-line treatment of advanced ovarian cancer might be the addition of noncross-resistant drugs to the two-drug regimen. Meta-analysis showed a survival benefit for platinum-anthracycline based combinations as compared to platinum-based combinations without anthracyclines. An AGO phase I/II trial compared epirubicin in combination with carboplatin and paclitaxel in untreated patients with gynecological malignancies. Based on the results of this study a randomized phase III trial together with the French GINECO group was conducted. The trial started 11/97 and was closed 11/99. All 1281 patients were randomized. Currently, 1132 end-of-therapy reports have been issued. Nine hundred eighty nine (87%) patients completed six cycles of treatment. Treatment and toxicity data are available for these patients. Three hundred thirty five patients had a measurable residual tumor after initial debulking surgery. Response data of 228 patients (111 ET-Carbo, 117 Carbo-T) are available.

  13. Pelvic inflammatory disease and risk of invasive ovarian cancer and ovarian borderline tumors

    DEFF Research Database (Denmark)

    Rasmussen, Christina B; Faber, Mette T; Jensen, Allan;

    2013-01-01

    The aim of the study was to examine the potential association between a history of pelvic inflammatory disease (PID) and risk of epithelial ovarian cancer or ovarian borderline tumors.......The aim of the study was to examine the potential association between a history of pelvic inflammatory disease (PID) and risk of epithelial ovarian cancer or ovarian borderline tumors....

  14. A phase 2, randomized, double-blind, placebo-controlled trial of clinical activity and safety of subcutaneous Å6 in women with asymptomatic CA125 progression after first-line chemotherapy of epithelial ovarian cancer

    DEFF Research Database (Denmark)

    Ghamande, Sharad A.; Silverman, Michael H.; Huh, Warner

    2008-01-01

    OBJECTIVES: A6 is a novel peptide that interferes with single-chain urokinase plasminogen activator activity and has shown anti-angiogenic, anti-migratory, and anti-invasive properties. We evaluated clinical efficacy and safety of subcutaneously administered A6 in women with epithelial ovarian...... cancer. METHODS: Women with epithelial ovarian, fallopian tube, or primary peritoneal cancer in clinical remission after first-line chemotherapy with 2 consecutive increases of CA125 values above normal but with no disease on physical examination or imaging studies were randomly assigned to receive daily...

  15. Serum and cystic fluid levels of soluble interleukin-2 receptor-alpha in patients with epithelial ovarian tumors are correlated

    NARCIS (Netherlands)

    de Bruijn, HWA; ten Hoor, KA; van der Zee, AGJ

    1998-01-01

    At the diagnosis of ovarian cancer, patients have higher serum levels of soluble interleukin-2 receptor-alpha (IL2R alpha) compared to patients with benign ovarian tumors or healthy blood donors (means of 750 vs. 469 and 390 U/ml, respectively, p <0.001), Serum levels were positively related to the

  16. CYP1B1, Oxidative Stress, and Inflammation in the Etiology of Ovarian Epithelial Cancer Using an Avian Model of Ovarian Carcinoma

    Science.gov (United States)

    2007-11-01

    ovarian cancer [8, 23, 24]. COX-1 275 has also been shown to be increased in feline oral squamous 276 cell carcinomas, the only non-gynecological carcinoma...expression in feline oral squamous cell car- 632cinoma. J. Comparat. Pathol. 135, 93–99 (2006) 63343. J.S. Richards, D.L. Russell, S. Ochsner, L.L...probes and reagents for analysis of chicken ovarian tissues . A. CYP1B1 i. The chicken CYP1B1 cDNA clone was purchased from Dr. Joan Burnside at the

  17. Review of epidemiological evidence for reproductive and hormonal factors in relation to the risk of epithelial ovarian malignancies.

    Science.gov (United States)

    Riman, Tomas; Nilsson, Staffan; Persson, Ingemar R

    2004-09-01

    Ovarian cancer is the leading cause of mortality related to gynecologic malignancies in Sweden but there is no current screening program. Based upon epidemiological research there is evidence that certain reproductive factors are associated with ovarian cancer risk. Most studies generally indicate that each childbirth incurs a 15-20% risk reduction. Women who have used oral contraceptives for 5 years or longer experience about half the risk of ovarian cancer compared with never users. Breastfeeding seems to be protective while age at menarche and at menopause are less consistent risk predictors. Tubal ligation and hysterectomy seem to reduce ovarian cancer risk by up to 80%. Although some studies found endometriosis, polycystic ovarian syndrome (PCOS) and pelvic inflammatory disease (PID) to be positively related to ovarian cancer, the role of these factors is not yet established. Most recent studies observed an approximately 50% ovarian cancer risk increase among ever users of hormone replacement therapy (HRT) compared with never users, and the risk increased further with long-term use. There is less information concerning separate estrogen and progestin effects of HRT and ovarian cancer risk. Although the cause of ovarian cancer remains obscure, hypotheses relating to "incessant" ovulation, excessive gonadotropin secretion, retrograde carcinogen transportation, apoptosis and estrogen/progestin imbalance have been invoked as etiological explanations. All these hypotheses find various epidemiological support. The aim of this review is to summarize the epidemiological findings on reproductive factors and ovarian cancer risk. These findings are considered in the context of etiologic hypotheses and some new research areas are suggested.

  18. Bilateral ovarian cystadenoma in a geriatric African elephant (Loxodonta africana).

    Science.gov (United States)

    Hoby, Stefan; Aloisio, Fabio; Schumacher, Vanessa L

    2014-06-01

    A 59-yr-old, captive female African elephant (Loxodonta africana) died of a cardiovascular collapse. Necropsy revealed bilateral replacement of the ovarian tissue by multiple cystic formations of up to 10 cm in diameter. The cysts were thin walled and filled with clear watery fluid. Smaller solid masses with an irregular surface projected from the wall of a few of the cysts. Histologically, the cystic structures were characterized by a single layer of well-differentiated cuboidal epithelial cells resting on a basement membrane. Occasionally the cysts contained nodular proliferations of single-layered, well-differentiated cuboidal epithelial cells forming anastomosing tubules and occasional papillary projections. The ovarian neoplasia was diagnosed as a bilateral multilocular serous ovarian cystadenoma. The nulliparous status and the advanced age may have contributed to the ovarian pathology.

  19. Diagnosis and Management of Peritoneal Metastases from Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Evgenia Halkia

    2012-01-01

    Full Text Available The management and the outcome of peritoneal metastases or recurrence from epithelial ovarian cancer are presented. The biology and the diagnostic tools of EOC peritoneal metastasis with a comprehensive approach and the most recent literatures data are discussed. The definition and the role of surgery and chemotherapy are presented in order to focuse on the controversial points. Finally, the paper discusses the new data about the introduction of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC in the treatment of advanced epithelial ovarian cancer.

  20. Polymorphism in the GALNT1 gene and epithelial ovarian cancer in non-Hispanic white women: the Ovarian Cancer Association Consortium

    DEFF Research Database (Denmark)

    Phelan, Catherine M; Tsai, Ya-Yu; Goode, Ellen L;

    2010-01-01

    Aberrant glycosylation is a well-described hallmark of cancer. In a previous ovarian cancer case control study that examined polymorphisms in 26 glycosylation-associated genes, we found strong statistical evidence (P = 0.00017) that women who inherited two copies of a single-nucleotide polymorphi...

  1. Expressions of SOX2 and CyclinD1 in epithelial ovarian cancer tissue%卵巢上皮性癌组织中 SOX2和 CyclinD1的表达

    Institute of Scientific and Technical Information of China (English)

    姚俊阁; 李红雨; 赵书君; 张慧; 张艳艳; 郭欢欢

    2014-01-01

    目的:检测卵巢上皮性癌组织中SOX2和CyclinD1的表达。方法:分别采用免疫组化SP法和RT-PCR法检测20例正常卵巢上皮组织、20例卵巢良性上皮性肿瘤组织及43例卵巢上皮性癌组织中SOX2和CyclinD1蛋白及mRNA的表达。结果:3种组织间SOX2、CyclinD1蛋白及mRNA的表达差异有统计学意义(蛋白:χ2=32.998,mRNA:F=454.222、398.284,P均<0.05);卵巢上皮性癌组织中SOX2、CyclinD1蛋白及mRNA的表达高于卵巢良性上皮性肿瘤组织及正常卵巢上皮组织( P均<0.05)。 SOX2、CyclinD1蛋白的表达均与卵巢上皮性癌FIGO分期、分化程度及淋巴结转移有关(P均<0.05)。卵巢上皮性癌组织中SOX2、CyclinD1蛋白的表达有关联(rp =0.422,P<0.05)。结论:SOX2和CyclinD1在卵巢上皮性癌组织中高表达,二者可能协同参与卵巢上皮性癌的发生及发展。%Aim:To explore the expressions and clinical significance of SOX 2 and CyclinD1 in epithelial ovarian canc-er tissue.Methods:Immunohistochemical SP method and RT-PCR were used to separately detect the expressions of SOX 2 and CyclinD1 in 20 cases of normal epithelial ovarian tissue , 20 cases of benign epithelial ovarian neoplasm tissue , and 43 cases of epithelial ovarian cancer tissue .Results:The expressions of SOX2 and CyclinD1 protein and mRNA in epithelial ovarian cancer tissue were significantly higher than those in benign epithelial ovarian neoplasm tissue and normal epithelial ovarian tissue(protein:χ2 =32.998;mRNA:F=454.222,398.284, all P<0.05).The expressions of SOX2 and CyclinD1 protein in epithelial ovarian cancer tissue were related to FIGO stage , histological differentiation and lymph node metastasis (P<0.05).The expression of SOX2 protein was associated with that of CyclinD1 protein in epithelial ovarian cancer tissue (rp =0.422,P<0.05).Conclusion: SOX2 and CyclinD1 are both over-expressed in epithelial ovarian cancer

  2. Standard first-line chemotherapy with or without nintedanib for advanced ovarian cancer (AGO-OVAR 12)

    DEFF Research Database (Denmark)

    du Bois, Andreas; Kristensen, Gunnar; Ray-Coquard, Isabelle

    2016-01-01

    the combination of nintedanib with standard carboplatin and paclitaxel chemotherapy in patients with newly diagnosed advanced ovarian cancer. METHODS: In this double-blind phase 3 trial, chemotherapy-naive patients (aged 18 years or older) with International Federation of Gynecology and Obstetrics (FIGO) IIB...

  3. Anticancer activity of NOB1-targeted shRNA combination with TRAIL in epithelial ovarian cancer cells.

    Science.gov (United States)

    Lin, Yang; Xu, Tianmin; Teng, Hong; Cui, Manhua

    2015-01-01

    Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) based strategy is a promising targeted therapeutic approach for the treatment of ovarian cancer. However, the effectiveness of the treatment remains limited due to the inherent or acquired resistance of tumor cells to TRAIL. Our previously study demonstrated that downregulation of NOB1 (NIN1/RPN12 binding protein 1 homolog) expression by a lentiviral short hairpin RNA (shRNA) delivery system (Lv/sh-NOB1) suppressed ovarian cancer growth. Here, Lv/sh-NOB1 and TRAIL were combined and tested the effects of this combination on ovarian cancer cells to identify more effective therapeutics against ovarian cancer by several in vitro experiments. Tumor growth ability in SKVO3 xenograft nude mice was also determined to define this combination treatment effect in tumorigenesis in vivo. In vitro assay showed that Lv/sh-NOB1 in combination with TRAIL treatment in ovarian cancer cell synergistically suppressed the proliferation and colony formation, as well as induced cell apoptosis and increased the activity of caspase-3, -8 and -9. In vivo assay showed that Lv/sh-NOB1 combination with TRAIL synergistically suppressed tumor growth of nude mice model. Importantly, we found that downregulation of NOB1 could upregulate DR5 expression and active MAPK pathway, which might contribute to increase sensitivity TRAIL to ovarian cancer cells. These findings suggested that Lv/sh-NOB1 combination with TRAIL treatment may be a potential treatment approach for ovarian cancer.

  4. Hemodynamic Consequences of Malignant Ascites in Epithelial Ovarian Cancer Surgery*: A Prospective Substudy of a Randomized Controlled Trial.

    Science.gov (United States)

    Hunsicker, Oliver; Fotopoulou, Christina; Pietzner, Klaus; Koch, Mandy; Krannich, Alexander; Sehouli, Jalid; Spies, Claudia; Feldheiser, Aarne

    2015-12-01

    Malignant ascites (MA) is most commonly observed in patients scheduled for epithelial ovarian cancer (EOC) surgery and is supposed as a major risk factor promoting perioperative hemodynamic deterioration. We aimed to assess the hemodynamic consequences of MA on systemic circulation in patients undergoing cytoreductive EOC surgery.This study is a predefined post-hoc analysis of a randomized controlled pilot trial comparing intravenous solutions within a goal-directed algorithm to optimize hemodynamic therapy in patients undergoing cytoreductive EOC surgery. Ascites was used to stratify the EOC patients prior to randomization in the main study. We analyzed 2 groups according to the amount of ascites (NLAS: none or low ascites [500 mL]). Differences in hemodynamic variables with respect to time were analyzed using nonparametric analysis for longitudinal data and multivariate generalized estimating equation adjusting the analysis for the randomized study groups of the main study.A total of 31 patients in the NLAS and 16 patients in the HAS group were analyzed. Although cardiac output was not different between groups suggesting a similar circulatory blood flow, the HAS group revealed higher heart rates and lower stroke volumes during surgery. There were no differences in pressure-based hemodynamic variables. In the HAS group, fluid demands, reflected by the time to reindication of a fluid challenge after preload optimization, increased steadily, whereas stroke volume could not be maintained at baseline resulting in hemodynamic instability after 1.5 h of surgery. In contrast, in the NLAS group fluid demands were stable and stroke volume could be maintained during surgery. Clinically relevant associations of the type of fluid replacement with hemodynamic consequences were particularly observed in the HAS group, in which transfusion of fresh frozen plasma (FFP) was associated to an improved circulatory flow and reduced vasopressor and fluid demands, whereas the

  5. Ten years of "Optimal Therapy in Advanced Ovarian Cancer. Update" meeting.

    Science.gov (United States)

    Poveda, A

    2008-01-01

    The International Symposium on Advanced Ovarian Cancer: Optimal Therapy was founded by Dr. Andrés Poveda and Prof. Jan B. Vermorken, and each edition has been directed by them. The 6th edition was held on March 2, 2007. This symposium is organized every other year by GEICO (Grupo Español de Investigación de Cáncer de Ovario/Spanish Ovarian Cancer Research Group), under the auspices of the Spanish Society of Medical Oncology (SEOM), the Gynecologic Cancer Intergroup (GCIG), and the European Society of Medical Oncology (ESMO) Educational Committee for its Medical Oncology Recertification Approval (ESMO/MORA) Program. One hundred and fifty people attended the symposium's 1st edition, held in 1996. Since then, the interest in this meeting has increased. Last year, almost three hundred people coming not only from Spain but also from Europe, North and Latin America, Asia, and Australia were present in the symposium. This is a great challenge for us. Some important international cooperative groups from Europe, America, and Australia collaborate with this symposium, such as GOG, NCIC, EORTC, AGO, Scottish Group, ICON, GINECO, NSGO, ANZGOG, and others.

  6. Discovery of specific metastasis-related N-glycan alterations in epithelial ovarian cancer based on quantitative glycomics.

    Directory of Open Access Journals (Sweden)

    Xingwang Zhang

    Full Text Available Generally, most of ovarian cancer cannot be detected until large scale and remote metastasis occurs, which is the major cause of high mortality in ovarian cancer. Therefore, it is urgent to discover metastasis-related biomarkers for the detection of ovarian cancer in its occult metastasis stage. Altered glycosylation is a universal feature of malignancy and certain types of glycan structures are well-known markers for tumor progressions. Thus, this study aimed to reveal specific changes of N-glycans in the secretome of the metastatic ovarian cancer. We employed a quantitative glycomics approach based on metabolic stable isotope labeling to compare the differential N-glycosylation of secretome between an ovarian cancer cell line SKOV3 and its high metastatic derivative SKOV3-ip. Intriguingly, among total 17 N-glycans identified, the N-glycans with bisecting GlcNAc were all significantly decreased in SKOV3-ip in comparison to SKOV3. This alteration in bisecting GlcNAc glycoforms as well as its corresponding association with ovarian cancer metastatic behavior was further validated at the glycotransferase level with multiple techniques including real-time PCR, western blotting, transwell assay, lectin blotting and immunohistochemistry analysis. This study illustrated metastasis-related N-glycan alterations in ovarian cancer secretome in vitro for the first time, which is a valuable source for biomarker discovery as well. Moreover, N-glycans with bisecting GlcNAc shed light on the detection of ovarian cancer in early peritoneal metastasis stage which may accordingly improve the prognosis of ovarian cancer patients.

  7. Identification of differentially expressed microRNAs in epithelial ovarian cancer%卵巢上皮癌差异表达microRNAs的筛选研究

    Institute of Scientific and Technical Information of China (English)

    雷磊; 王艳丽; 梁静; 赵西侠; 王国庆

    2013-01-01

    Objective: Identifying the differentially expressed microRNAs in epithelial ovarian cancer compared with the adjacent tissues using microarray chip technology, and study the molecular mechanism in the development and progress of epithelial ovarian cancer. Methods: Eight pairs of epithelial ovarian cancer and adjacent normal tissues were obtained from patients undergoing surgery from June 2010 to June 2011 in the Center of women's tumors of Shaanxi Tumor Hospital. Total RNA was extracted and microRNAs microarray chip was used to screen the differentially expressed microRNAs. Real - time quantitative PCR was used to verify the microarray chip results. Then tumor - related genes targeted by the microRNAs were predicted by the microRNAs database. Results:Four microRNAs,miR -146a,miR -200c,miR -221 and miR -429 were significantly up - regulated and miR - 34b was significantly down - regulated combining the results of microarray chip and real - time quantitative PCR. Several tumor - related target genes were searched by the prediction database. Conclusion: Characterizing the differentially expressed microRNAs and target genes in epithelial ovarian cancer may provide a potential role for the carcinogenesis of epithelial ovarian cancer.%目的:利用microRNA微阵列芯片技术筛选卵巢上皮癌及癌旁组织中差异表达的microRNAs,发现与卵巢上皮癌相关的microRNAs,为进一步阐明卵巢上皮癌发生发展的分子机制提出依据.方法:选取2010年6月至2011年6月在陕西省肿瘤医院妇瘤中心行手术治疗的8例卵巢上皮癌及对应癌旁组织,提取组织总RNA,采用microRNA芯片杂交技术检测卵巢上皮癌及对应癌旁组织中microRNAs表达水平,经统计分析寻找可能的差异表达的microRNAs,应用实时定量PCR方法验证芯片结果.利用microRNA靶基因预测数据库检索得到差异表达microRNAs与肿瘤相关的靶基因.结果:结合芯片与实时定量PCR结果,筛选获得miR-146a、miR-200c

  8. Mammaglobin B is an independent prognostic marker in epithelial ovarian cancer and its expression is associated with reduced risk of disease recurrence

    Directory of Open Access Journals (Sweden)

    Bandiera Elisabetta

    2009-07-01

    Full Text Available Abstract Background Traditional prognostic factors in epithelial ovarian cancer (EOC are inadequate in predicting recurrence and long-term prognosis, but genome-wide cancer research has recently provided multiple potentially useful biomarkers. The gene codifying for Mammaglobin B (MGB-2 has been selected from our previous microarray analysis performed on 19 serous papillary epithelial ovarian cancers and its expression has been further investigated on multiple histological subtypes, both at mRNA and protein level. Since, to date, there is no information available on the prognostic significance of MGB-2 expression in cancer, the aim of this study was to determine its prognostic potential on survival in a large cohort of well-characterized EOC patients. Methods MGB-2 expression was evaluated by quantitative real time-PCR in fresh-frozen tissue biopsies and was validated by immunohistochemistry in matched formalin fixed-paraffin embedded tissue samples derived from a total of 106 EOC patients and 27 controls. MGB-2 expression was then associated with the clinicopathologic features of the tumors and was correlated with clinical outcome. Results MGB-2 expression was found significantly elevated in EOC compared to normal ovarian controls, both at mRNA and protein level. A good correlation was detected between MGB-2 expression data obtained by the two different techniques. MGB-2 expressing tumors were significantly associated with several clinicopathologic characteristics defining a less aggressive tumor behavior. Univariate survival analysis revealed a decreased risk for cancer-related death, recurrence and disease progression in MGB-2-expressing patients (p Conclusion This is the first report documenting that MGB-2 expression characterizes less aggressive forms of EOC and is correlated with a favorable outcome. These findings suggest that the determination of MGB-2, especially at molecular level, in EOC tissue obtained after primary surgery can

  9. Early Detection of Ovarian Cancer with Conventional and Contrast-Enhanced Transvaginal Sonography: Recent Advances and Potential Improvements

    Directory of Open Access Journals (Sweden)

    Arthur C. Fleischer

    2012-01-01

    Full Text Available Recently, there have been several major technical advances in the sonographic diagnosis of ovarian cancer in its early stages. These include improved assessment of tumor morphology with transvaginal sonography (TVS, and detection and characterization of tumor neovascularity with transvaginal color Doppler sonography (TV-CDS and contrast-enhanced transvaginal sonography (CE-TVS. This paper will discuss and illustrate these improvements and describe how they enhance detection of early-stage ovarian cancer. Our initial experience with parametric mapping of CE-TVS will also be mentioned.

  10. Carboplatin (JM 8), adriamycin and cyclophosphamide (JAC) in advanced ovarian carcinoma: a pilot study.

    Science.gov (United States)

    Conte, P F; Bruzzone, M; Chiara, S; Rosso, R; Giaccone, G; Carnino, F; Guercio, E; Ragni, N; Foglia, G; Bentivoglio, G

    1988-04-30

    Eleven untreated patients with advanced ovarian cancer were studied for tolerance and response to combination treatment with fixed doses of adriamycin (45 mg/m2) and cyclophosphamide (600 mg/m2) + escalating doses of carboplatin. At the first dose level of carboplatin (200 mg/m2), toxicity was acceptable. With carboplatin at 300 mg/m2, severe hematologic toxicity was observed. The dose-limiting toxicity was leukopenia. Although carboplatin was administered without any hydration, no patient experienced renal toxicity. Eight objective responses were observed in 9 clinically evaluable patients. At second look surgery, 3 complete responses and 4 partial responses were documented. Polychemotherapy with JAC (carboplatin, 200 mg/m2, adriamycin, 45 mg/m2, and cyclophosphamide, 600 mg/m2) is administrable with acceptable toxicity.

  11. Feasibility Evaluation for Selection of Neoadjuvant Chemotherapy before Cytoreduction of Advanced Ovarian Carcinoma

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Ovarian carcinoma is one of three gynecological neoplasms. It typically develops as an insidious disease, with few warning signs or symptoms, because the ovary is situated at a deep part of the pelvic cavity. Advanced ovarian carcinoma (AOC) is highly malignant, so the prognosis of the patients is poor. Initial debulking surgery, followed by chemotherapy,is currently the main therapeutic choice for AOC. During operations, efforts should be made to excise the tumor and minimize the residual lesion, so as to achieve the optimal cytoreduction and improve the prognosis. As a feasible therapeutic regimen for the patients with primary unresectable AOC,neoadjuvant chemotherapy can improve the surgical condition and can increase the optimality of cytoreduction. It is important therefore to evaluate the feasibility of surgical treatment and make a proper selection of the primary treatment plan and neoadjuvant chemotherapy, so as to enhance the optimality of surgery and to avoid unnecessary exploratory laparotomy. At present, methods of feasibility evaluation for optimal cytoreduction of AOC are as follows: 1) radiography, i.e., CT, PET and MRI scanning; 2) CA-125 value;3) laparoscopic exploration; 4) other tumor markers such as p53. However,any method lacks the ability to cover all the predicting factors influencing the outcome of cytoreduction, and to evaluate the surgery across the board.Searching for new methods and combining two or more procedures to evaluate the feasibility of cytoreduction may increase the optimality, reduce the residual focus, prolong survival time and improve the prognosis. In this study,recent advances in evaluation of the feasibility for optimal cytoreduction and the selection of neoadjuvant chemotherapeutic regimens were reviewed.

  12. Expression and clinical significance of TrkB and its ligand BDNF in epithelial ovarian cancer%TrkB及其配体BDNF在卵巢上皮癌中的表达及其临床意义

    Institute of Scientific and Technical Information of China (English)

    李明伟; 刘继红

    2012-01-01

    Objective The current study was to explore the expression profile of TrkB/BDNF in ovarian epithelial cancer and their correlation with clinical pathology variables respectively. Methods TrkB/BDNF were examined in 10 normal ovarian, 17 benign ovarian epithelial tumor, 21 borderline ovarian epithelial tumor and 60 ovarian epithelial cancer tissue samples by immunohistochemical Streptomycin avidin - peroxidase (SP) method. Results The expression of TrkB and BDNF were negative in normal ovarian tissue and benign epithelial tumors, and the expression rate of TrkB and BDNF in borderline ovarian tumors and ovarian epithelial cancers (EOC) was 19. 0%, 71. 7% and 14. 0%, 51. 7% (P<0. 05) . The degree of TrkB/BDNF express was more strong in G3, I+F stage EOC than that in G1+G2, I + H stage EOC (P<0. 05) . TrkB expression was positively correlated with BDNF level in epithelial ovarian cancer (r=0. 43, Povarian epithelial cancer. TrkB may synergy with BDNF to promote tumorigenesis and development of epithelial ovarian cancer, it may be a target for EOC gene therapy.%目的 检测酪氨酸激酶B (tyrosine kinase,TrkB)及其配体脑源性神经营养因子(brain -derived neurotrophic factor,BDNF)在卵巢上皮癌(EOC)中的表达,并探讨其临床意义.方法 选择中山大学附属肿瘤医院病理存档的石蜡标本108例,其中10例正常卵巢、17例良性卵巢肿瘤、21例卵巢交界性肿瘤和60例卵巢上皮癌,采用免疫组化链霉素抗生物素蛋白-过氧化物酶法(SP法)检测TrkB及其配体BDNF蛋白的表达水平,分析其与临床病理因素之间的关系.结果 TrkB和BDNF蛋白在正常卵巢组织和良性卵巢上皮性肿瘤中无表达;在交界性和卵巢上皮性癌中的阳性表达率分别为19.0%、71.7%和14.0%、51.7%(P<0.05).TrkB和BDNF蛋白在EOC组中的表达水平与其FIGO分期及病理分级有关,在Ⅲ期+Ⅳ期、低分化组(G3)比

  13. 胞质HuR在卵巢上皮性癌的表达及意义%The expression and significance of cytoplasmic HuR in epithelial ovarian carcinoma

    Institute of Scientific and Technical Information of China (English)

    齐玉明; 石彬; 郭皓; 成艳梅

    2011-01-01

    Objective To investigate the correlation between the expression of HuR in epithelial ovarian cancer and clinicopathological parameters in order to explore the factors that affect the prognosis of patients with epithelial ovarian carcinoma. Methods The expressions of cytoplasmic and nuclear HuR in normal ovary tissues,borderline tissue of ovary tumor and epithelial ovarian carcinoma were detected by SP immunohistochemical technique and RT-PCR. The relationship between cytoplasmic HuR expression and prognostic factors was analyzed.Results The expressions of cytoplasmic and nuclear HuR in epithelial ovarian cancer tissue were significantly higher than those in borderline tissue of epithelial ovarian tumor and normal ovarian tissues,however,there was no significant difference between the borderline tissue of epithelial ovarian tumor and normal ovarian tissue ( P >0.05). The statistical analysis showed that the positive expression rate of cytoplasmic HuR in epithelial ovarian carcinoma was closely correlated with histological grade and FIGO stage, but the positive expression rate of nuclear HuR was not correlated with the clinicopathological parameters. Conclusion The over-expression of HuR may play an important role in the growth and progress of epithelial ovarian carcinoma. To detect the expression of cytoplasmic HuR in epithelial ovarian carcinoma may predict the characteristics of oncobiology behaviour. The expression of cytoplasmic HuR may act as an independent prognostic indicator.%目的 检测HuR在卵巢上皮性癌中的表达及与临床病理参数的关系,寻求卵巢癌的预后因素.方法 采用免疫组化链霉菌抗生物素蛋白-过氧化物酶连接(SP)法和逆转录RT-PCR技术,检测胞质和胞核HuR在正常、交界性、恶性卵巢组织中的表达;分析胞质HuR的表达与预后的关系.结果 胞质和胞核HuR在恶性卵巢肿瘤组织的表达明显高于交界性卵巢肿瘤和正常卵巢组织,胞质和胞核HuR在交界性

  14. 上皮性卵巢癌危险因素的研究%A study on risk factors for epithelial ovarian cancer

    Institute of Scientific and Technical Information of China (English)

    张巧利

    2001-01-01

    目的 探讨上皮性卵巢癌的危险因素。方 法 采用1∶2匹配的病例-对照研究。于1997~1998年,在江苏南通市和连云港 市 共选取经病理学检查确诊的原发性上皮性卵巢癌住院病人103例,对照206例。结果  单因素条件logistic回归分析表明:高产次、月经初潮晚、哺乳时间长及体重指 数(BMI)高可能是保护因素;使用宫内节育器以及使用时间长、有妇科恶性 肿瘤家族史及染发次数多可能为危险因素。在进行多因素模型拟合时,产次、染发、使用宫 内节育器、哺乳及职业5个因素进入了方程。结论  结果从总体上支持Fathalla 的排卵假说;上皮性卵巢癌与卵巢恶性肿瘤(未进行病理分 型)的危险因素基本一致。%Objective To illustrate risk factors for epithe lial ovarian cancer. Methods An 1∶2 matched hospital-based ca s e-control study was conducted between 1997 and 1998 in Nantong and Lianyungang city, Jiangsu. The study included 103 pathologically confirmed primary epithel ial ovarian cancer cases and 206 controls. Results Single-fac tor conditional logistic regression analysis showed that parity, late age of men arche, long breast feeding duration and high body mass index(BMI) were protect ive factors for the disease, while intrauterine device(IUD) use, IUD use duratio n, family history of gynecological malignant tumors and hair dyeing were risk fa c tors for epithelial ovarian cancer. Parity, hair dyeing, IUD use, breast feeding and occupation entered multiple-factor regression model. Conclusions The result tends to support Fathalla's theory of incessant ovulation and n o difference was found in risk factors between epithelial ovarian cancer and ova rian malignant tumor.

  15. Knockdown of STAT3 by iRNA Inhibiting Migration and Invasion of Epithelial Ovarian Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    LI Qin-hua; ZHU Ji-hong; LIU Lei; YUE Ying

    2012-01-01

    Signal transducer and activator of transcription 3(STAT3) is a dual functional transcription factor with the functions of signal transduction and transcription regulation.It is reported that the expression of STAT3 in ovarian cancer is significantly higher and STAT3 can facilitate ovarian cancer growth and metastasis.To clarify the definite effect and molecular mechanism of STAT3 involved in ovarian cancer growth and metastasis,STAT3 expression was significantly downregulated by transfeeting ovarian cancer model SK-OV-3 cells with the plasmid vector which express specific RNAi that targets human STAT3.The downregulated STAT3 not only decreased the invasion and migration but also inhibited the proliferation of SK-OV-3 cells.Western blot assay shows that the expression of vascular endothelial growth factor(VEGF) and that of Survivin were reduced in the cells with the plasma vector expressing specific RNAi that targets human STATY These results demonstrate that STAT3 involved in the invasion and migration of SK-OV-3 regulates the expression of VEGF and Survivin.In addition,VEGF and Survivin could play an important role in ovarian cancer growth and metastasis.

  16. Toxicities of different first-line chemotherapy regimens in the treatment of advanced ovarian cancer

    Science.gov (United States)

    Qu, Chang-Ping; Sun, Gui-Xia; Yang, Shao-Qin; Tian, Jun; Si, Jin-Ge; Wang, Yi-Feng

    2017-01-01

    Abstract Background: Ovarian cancer (OC) is the 5th leading cause of cancer-related deaths around the world, and several chemotherapy regimens have been applied in the treatment of OC. We aim to compare toxicities of different chemotherapy regimens in the treatment of advanced ovarian cancer (AOC) using network meta-analysis. Methods: Literature research in Cochrane Library, PubMed, and EMBASE was performed up to November 2015. Eligible randomized controlled trials (RCTs) of different chemotherapy regimens were included. Network meta-analysis combined direct and indirect evidence to assess pooled odds ratios (ORs) and draw the surface under the cumulative ranking (SUCRA) curves. Results: Thirteen eligible RCTs were included in this network meta-analysis, including 8 chemotherapy regimens (paclitaxel + carboplatin [PC], pegylated liposomal doxorubicin [PLD] + carboplatin, carboplatin, gemcitabine + carboplatin, paclitaxel, PC + epirubicin, PC + topotecan, docetaxel + carboplatin). Gemcitabine + carboplatin regimen exerted higher incidence of anemia when compared with carboplatin and paclitaxel regimens. The incidence of febrile neutropenia of gemcitabine + carboplatin regimen was higher than that of PC, PLD + carboplatin, carboplatin, and PC + topotecan regimens. Topotecan PC + epirubicin regimen had a higher toxicity, comparing with PC, PLD + carboplatin, and PC + topotecan regimens. As for thrombocytopenia, gemcitabine + carboplatin chemotherapy regimen produced an obviously higher toxicity than PC and carboplatin. As for nausea, PLD + carboplatin chemotherapy regimen had a significantly higher toxicity than that of carboplatin chemotherapy regimen. Moreover, when compared with PC and carboplatin chemotherapy regimens, the toxicity of PC + epirubicin was greatly higher to patients with AOC. Conclusion: The nonhematologic toxicity of PLD + carboplatin regimen was higher than other regimens, which

  17. Panitumumab and pegylated liposomal doxorubicin in platinum-resistant epithelial ovarian cancer with KRAS wild-type

    DEFF Research Database (Denmark)

    Steffensen, Karina Dahl; Waldstrøm, Marianne; Pallisgård, Niels;

    2013-01-01

    OBJECTIVE: The increasing number of negative trials for ovarian cancer treatment has prompted an evaluation of new biologic agents, which in combination with chemotherapy may improve survival. The aim of this study was to investigate the response rate in platinum-resistant, KRAS wild-type ovarian...... cancer patients treated with pegylated liposomal doxorubicin (PLD) supplemented with panitumumab. PATIENTS AND METHODS: Major eligibility criteria were relapsed ovarian/fallopian/peritoneal cancer patients with platinum-resistant disease, measurable disease by GCIG CA125 criteria and KRAS wild-type......-free and overall survival in the intention-to-treat population was 2.7 months (2.5-3.2 months, 95% confidence interval) and 8.1 months (5.6-11.7 months, 95% confidence interval), respectively. The most common treatment-related grade 3 toxicities included skin toxicity (42%), fatigue (19%), and vomiting (12...

  18. Ovarian cancer linked to lynch syndrome typically presents as early-onset, non-serous epithelial tumors

    DEFF Research Database (Denmark)

    Bartuma, Katarina; Bernstein, Inge; Malander, Susanne

    2011-01-01

    OBJECTIVE: Heredity is a major cause of ovarian cancer and during recent years the contribution from germline mismatch repair (MMR) gene mutations linked to Lynch syndrome has gradually been recognized. METHODS: We characterized clinical features, tumor morphology and mismatch repair defects in all....... The underlying MMR gene mutations in these families affected MSH2 in 49%, MSH6 in 33% and MLH1 in 17%. Immunohistochemical loss of the corresponding MMR protein was demonstrated in 33/36 (92%) tumors analyzed. CONCLUSION: The combined data from our cohorts demonstrate that ovarian cancer associated with Lynch...

  19. Pilot study of a heptavalent vaccine-keyhole limpet hemocyanin conjugate plus QS21 in patients with epithelial ovarian, fallopian tube, or peritoneal cancer

    DEFF Research Database (Denmark)

    Sabbatini, Paul J; Ragupathi, Govind; Hood, Chandra;

    2007-01-01

    PURPOSE: To characterize the safety and immunogenicity of a heptavalent antigen-keyhole limpet hemocyanin (KLH) plus QS21 vaccine construct in patients with epithelial ovarian, fallopian tube, or peritoneal cancer in second or greater complete clinical remission. EXPERIMENTAL DESIGN: Eleven...... patients in this pilot trial received a heptavalent vaccine s.c. containing GM2 (10 microg), Globo-H (10 microg), Lewis Y (10 microg), Tn(c) (3 microg), STn(c) (3 microg), TF(c) (3 microg), and Tn-MUC1 (3 microg) individually conjugated to KLH and mixed with adjuvant QS21(100 microg). Vaccinations were......). RESULTS: Eleven patients were included in the safety analysis; 9 of 11 patients remained on study for at least 2 weeks past fourth vaccination and were included in the immunologic analysis (two withdrew, disease progression). The vaccine was well tolerated. Self-limited and mild fatigue (maximum grade 2...

  20. The Potential Mechanisms Underlying Aspirin-induced Inhibition of Ovarian Tumor Cell Growth

    Institute of Scientific and Technical Information of China (English)

    Yu LIU; Jin KE; Shi-Quan LIU; Fu-Xiang ZHOU; Cong-Hua XIE; Yun-Feng ZHOU

    2005-01-01

    @@ 1 Introduction Ovarian cancer remains the most lethal disease of the gynecological cancers. Owing to the lack of an effective screening approach combined with inadequate therapeutic approach for advanced disease, fewer than 25% of ovarian cancers are identified at an early curable stage. Thus these make ovarian cancer a strong candidate for chemoprevention. In 2001, Akhmedkhanov et al. demonstrated a 2-3 folds decrease in epithelial ovarian cancer associated with Aspirin use. These epidemiological observations suggest that an improved understanding of the mechanisms by which NSAID may decrease the development of ovarian cancer could lead to improved approaches for chemoprevention of this deadly disease. In this research, we explored the potential mechanism underlying epidemiological observations that ovarian cancer occurs at a lower frequency in women exposed to Aspirin(ASP).

  1. Lentiviral CRISPR/Cas9 vector mediated miR-21 gene editing inhibits the epithelial to mesenchymal transition in ovarian cancer cells

    Science.gov (United States)

    Huo, Wenying; Zhao, Guannan; Yin, Jinggang; Ouyang, Xuan; Wang, Yinan; Yang, Chuanhe; Wang, Baojing; Dong, Peixin; Wang, Zhixiang; Watari, Hidemichi; Chaum, Edward; Pfeffer, Lawrence M.; Yue, Junming

    2017-01-01

    CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats) mediated genome editing is a powerful approach for loss of function studies. Here we report that lentiviral CRISPR/Cas9 vectors are highly efficient in introducing mutations in the precursor miRNA sequence, thus leading to the loss of miRNA expression and function. We constructed four different lentiviral CRISPR/Cas9 vectors that target different regions of the precursor miR-21 sequence and found that these lentiviral CRISPR/Cas9 miR-21 gRNA vectors induced mutations in the precursor sequences as shown by DNA surveyor mutation assay and Sanger sequencing. Two miR-21 lentiviral CRISPR/Cas9 gRNA vectors were selected to probe miR-21 function in ovarian cancer SKOV3 and OVCAR3 cell lines. Our data demonstrate that disruption of pre-miR-21 sequences leads to reduced cell proliferation, migration and invasion. Moreover, CRISPR/Cas9-mediated miR-21 gene editing sensitizes both SKOV3 and OVCAR3 cells to chemotherapeutic drug treatment. Disruption of miR-21 leads to the inhibition of epithelial to mesenchymal transition (EMT) in both SKOV3 and OVCAR3 cells as evidenced by the upregulation of epithelial cell marker E-cadherin and downregulation of mesenchymal marker genes, vimentin and Snai2. The miR-21 target genes PDCD4 and SPRY2 were upregulated in cells transduced with miR-21gRNAs compared to controls. Our study indicates that lentiviral CRISPR/Cas9-mediated miRNA gene editing is an effective approach to address miRNA function, and disruption of miR-21 inhibits EMT in ovarian cancer cells. PMID:28123598

  2. Lentiviral CRISPR/Cas9 vector mediated miR-21 gene editing inhibits the epithelial to mesenchymal transition in ovarian cancer cells.

    Science.gov (United States)

    Huo, Wenying; Zhao, Guannan; Yin, Jinggang; Ouyang, Xuan; Wang, Yinan; Yang, Chuanhe; Wang, Baojing; Dong, Peixin; Wang, Zhixiang; Watari, Hidemichi; Chaum, Edward; Pfeffer, Lawrence M; Yue, Junming

    2017-01-01

    CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats) mediated genome editing is a powerful approach for loss of function studies. Here we report that lentiviral CRISPR/Cas9 vectors are highly efficient in introducing mutations in the precursor miRNA sequence, thus leading to the loss of miRNA expression and function. We constructed four different lentiviral CRISPR/Cas9 vectors that target different regions of the precursor miR-21 sequence and found that these lentiviral CRISPR/Cas9 miR-21 gRNA vectors induced mutations in the precursor sequences as shown by DNA surveyor mutation assay and Sanger sequencing. Two miR-21 lentiviral CRISPR/Cas9 gRNA vectors were selected to probe miR-21 function in ovarian cancer SKOV3 and OVCAR3 cell lines. Our data demonstrate that disruption of pre-miR-21 sequences leads to reduced cell proliferation, migration and invasion. Moreover, CRISPR/Cas9-mediated miR-21 gene editing sensitizes both SKOV3 and OVCAR3 cells to chemotherapeutic drug treatment. Disruption of miR-21 leads to the inhibition of epithelial to mesenchymal transition (EMT) in both SKOV3 and OVCAR3 cells as evidenced by the upregulation of epithelial cell marker E-cadherin and downregulation of mesenchymal marker genes, vimentin and Snai2. The miR-21 target genes PDCD4 and SPRY2 were upregulated in cells transduced with miR-21gRNAs compared to controls. Our study indicates that lentiviral CRISPR/Cas9-mediated miRNA gene editing is an effective approach to address miRNA function, and disruption of miR-21 inhibits EMT in ovarian cancer cells.

  3. RPS6KA2, a putative tumour suppressor gene at 6q27 in sporadic epithelial ovarian cancer

    DEFF Research Database (Denmark)

    Bignone, P A; Lee, K Y; Liu, Y

    2007-01-01

    -activated protein kinase pathway. It is expressed in normal ovarian epithelium, whereas reduced or absent in tumours or cell lines. We show that RPS6KA2 is monoallelically expressed in the ovary suggesting that loss of a single expressed allele is sufficient to cause complete loss of expression in cancer cells...

  4. Research on the expression and significance of Kras and P53 in epithelial ovarian carcinoma%卵巢上皮性癌中Kras和P53的表达及临床意义

    Institute of Scientific and Technical Information of China (English)

    张艳; 刘剑; 茅国新; 刘益飞

    2014-01-01

    Object ive: To investigate the expression and significance of Kras protein and P53 protein between normal ovarian tissue and epithelial ovarian carcinoma as well as their association with clinicopathologic features. Methods:90 cases were collected to study, including 80 cases with epithelial ovarian carcinoma and 10 cases of non-neoplastic ovarian tissue. Immunohistochemical methods were used to detect the expression of Kras and P53. Results:The positive expression rate of Kras between non-neoplastic ovarian tissue and epithelial ovarian carcinoma was 0.00% and 18.75%. The positive expression rate of P53 between non-neoplastic ovarian tissue and epithelial ovarian carcinoma was 0.00%and 38.75%.The expression of Kras in epithelial ovarian carcinoma was associated with the histologic grade amd the clinical stage, and not correlated with age and lymphatic metastasis. The expression of P53 in epithelial ovarian carcinoma was associated with the histologic grade, the clinical stage, and the lymphatic metastasis, and not correlated with age. Conclusions:The expression of Kras protein in low-grade epithelial ovarian carcinoma was higher than that in high-grade epithelial ovarian carcinoma and in the early stage, indicating that the role of Kras was important in the low-grade epithelial ovarian carcinoma. The expression of P53 protein in high-grade epithelial ovarian carcinoma was higher than that in low-grade epithelial ovarian carcinoma. The high expression of P53 protein usually was seen more in the late clinical stage,and associated with lymph node metastasis, which provided cogent evidence that the development of high-grade epithelial ovarian carcinoma was possibly related with P53 gene mutation.%目的:探讨Kras和P53蛋白在卵巢上皮性癌中的表达及与临床病理特征关系。方法:采用免疫组织化学SP法分别检测Kras、P53蛋白在非肿瘤性卵巢上皮组织10例及卵巢上皮性癌80例组织中的表达,并分析2种蛋白与临

  5. Snail介导的EMT在上皮性卵巢癌组织中的作用%Effects of Snail mediated EMT in epithelial ovarian carcinoma

    Institute of Scientific and Technical Information of China (English)

    唐青; 侯建青

    2014-01-01

    Objective To Study the effect on Snail mediated epithelial mesenchymal transition (EMT) in ovarian cancer occurrence, development and metastasis. Methods Immunohistochemical staining was detected Snail, E-cadherin,in 48 cases of ovarian serous adenocarcinoma,ovarian serous borderline tumors and ovarian serous adenomas Vimentin,investigate the correlation between the expression of EMT -related factors and the strength and relationship between clinicopathological features. Results(1)The expression of Snail,Vimentin in ovarian serous adenocarcinoma was 68.75% and 66.67%,higher than in borderline serous ovarian tumors (41.67% and 37.50) and in ovarian serous adenomas( 25.00%and 18.75%),with significant difference(P 0.05).(2)The expression level of Snail and FIGO, E-cadherin and Vimentin staging,differentiation level,there was no lymph node metastasis and peritoneal implants.(3)in ovarian serous adenocarcinoma, the expression of Snail positively correlated with Vimentin (r=0.477,P < 0.05),the expression of Snail was negatively correlated with E-cadherin(r=-0.601,P < 0.05),and the expression of E-cadherin and Vimentin correlation is not obvious(r=-0.206,P< 0.05). Conclusion In epithelial ovarian cancer,Snail,Vimentin upregulation,E-cadherin downregulation,suggesting that Snail-mediated EMT may be transferred with ovarian cancer,development and infiltration.%目的:检测Snail、E-cadherin及Vimentin在上皮性卵巢癌组织中的表达,探讨Snail介导的上皮间质转化(EMT)在卵巢癌发生、发展及转移中的作用。方法采用免疫组化法分别检测Snail、E-cadherin、Vimentin在48例卵巢浆液性腺癌、卵巢交界性浆液性肿瘤及卵巢浆液性腺瘤中的表达,探讨EMT相关因子表达强度的相关性及与临床病理特征之间的关系。结果(1)Snail、Vimentin在卵巢浆液性腺癌中的表达率为(68.75%/66.67%),高于卵巢交界性浆液性腺瘤的(41.67%/37.50%)及卵巢浆液性腺瘤的(25

  6. The effect of consolidation treatment with intraperitoneal carboplatin in advanced epithelial ovarian cancers

    Directory of Open Access Journals (Sweden)

    Azamsadat Mousavi

    2014-07-01

    Conclusion: It seems that consolidation therapy with intraperitoneal carboplatin may not increase overall survival, reduce relapse rate or decrease mortality, though it does not induce considerable side effects. Since the mean survival in the intervention group was nine months more than controls, this difference may be clinically significant.

  7. Microarray-Based oncogenic pathway profiling in advanced serous papillary ovarian carcinoma

    NARCIS (Netherlands)

    X.B. Trinh; W.A.A. Tjalma (Wiebren); L. Dirix (Luc); P.B. Vermeulen; D. Peeters (Dieter); D. Bachvarov (Dimcho); M. Plante (Marie); P.M.J.J. Berns (Els); J. Helleman (Jozien); S.J. van Laere; P.A. van Dam

    2011-01-01

    textabstractIntroduction: The identification of specific targets for treatment of ovarian cancer patients remains a challenge. The objective of this study is the analysis of oncogenic pathways in ovarian cancer and their relation with clinical outcome. Methodology: A meta-analysis of 6 gene expressi

  8. Misregulation of polo-like protein kinase 1, P53 and P21WAF1 in epithelial ovarian cancer suggests poor prognosis.

    Science.gov (United States)

    Zhang, Ruitao; Shi, Huirong; Ren, Fang; Liu, Huina; Zhang, Minghui; Deng, Youxing; Li, Xia

    2015-03-01

    Polo-like protein kinase 1 (PLK1), P53 and P21WAF1 are relevant to cell cycle checkpoints and cancer biology. Misregulation of PLK1, P53 and P21WAF1 has been detected in several types of malignant tumors. The present study aimed to clarify the role of PLK1, P53 and P21WAF1 in the prognosis of ovarian cancer. PLK1 and P53 shRNA lentiviral plasmids were transfected into SK-OV-3 cells, respectively. Cell proliferation, apoptosis and invasion were examined by MTT assay, flow cytometry and Matrigel assay, respectively. Survival time of the animals was observed in a xenograft model. Expression levels of PLK1, P53 and P21WAF1 were detected in different ovarian tissues by immunohistochemistry and western blot analysis. Their correlations to the clinicopathologic characteristics of the epithelial ovarian cancer (EOC) cases and their interrelationships were analyzed. Risk factors of prognosis for EOC were determined by logistic regression analysis. The survival time of EOC patients was measured by Kaplan-Meier analysis. After PLK1 or P53 knockdown, proliferation of the SK-OV-3 cells was inhibited, the apoptosis rate was increased, and cell invasion was suppressed in vitro, and the survival time was prolonged in the animals. Expression levels of P53, p-P53 (Ser15), P21WAF1, growth arrest and DNA damage‑inducible gene 45 (GADD45) and 14-3-3σ were upregulated in the SK-OV-3 cells after PLK1 knockdown, but downregulated after P53 knockdown. Higher expression levels of PLK1 and P53 were observed in patients with a higher FIGO stage and worse histological differentiation, but lower P21WAF1 was noted at a higher FIGO stage. Negative correlations were observed between expression of PLK1 and P53 and P53 and P21WAF1 in the EOC cases. PLK1, P53 and P21WAF1 could be used to assess the prognosis of EOC, respectively, but only PLK1 was found to be an independent prognostic factor. The overall survival time of subjects exhibiting PLK1-positive/P53-positive expression and PLK1-positive

  9. Telomere length is a prognostic biomarker in elderly advanced ovarian cancer patients: a multicenter GINECO study

    Science.gov (United States)

    Falandry, Claire; Horard, Béatrice; Bruyas, Amandine; Legouffe, Eric; Cretin, Jacques; Meunier, Jérôme; Alexandre, Jérôme; Delecroix, Valérie; Fabbro, Michel; Certain, Marie-Noëlle; Maraval-Gaget, Raymonde; Pujade-Lauraine, Eric; Gilson, Eric; Freyer, Gilles

    2015-01-01

    Purpose Age induces a progressive decline in functional reserve and impacts cancer treatments. Telomere attrition leads to tissue senescence. We tested the hypothesis that telomere length (TL) could predict patient vulnerability and outcome with cancer treatment. Patients and methods An ancillary study in the Elderly Women GINECO Trial 3 was performed to evaluate the impact of geriatric covariates on survival in elderly advanced ovarian cancer patients receiving six cycles of carboplatin. TL was estimated from peripheral blood at inclusion using standard procedures. Results TL (in base pairs) was estimated for 109/111 patients (median 6.1 kb; range [4.5-8.3 kb]). With a cut-off of 5.77 kb, TL discriminated two patient groups, long telomere (LT) and short telomeres (ST), with significantly different treatment completion rates of 0.80 (95%CI [0.71-0.89]) and 0.59 (95%CI [0.41-0.76]), respectively (odds ratio [OR]=2.8, p=0.02). ST patients were at higher risk of serious adverse events (SAE, OR=2.7; p=0.02) and had more unplanned hospital admissions (OR=2.1; p=0.08). After adjustment on FIGO stage, TL shorter than 6 kb was a risk factor of premature death (HR=1.57; p=0.06). Conclusion This exploratory study identifies TL as predictive factor of decreased treatment completion, SAE risk, unplanned hospital admissions and OS after adjustment on FIGO stage. PMID:26638179

  10. Multi-center evaluation of post-operative morbidity and mortality after optimal cytoreductive surgery for advanced ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Arash Rafii

    Full Text Available PURPOSE: While optimal cytoreduction is the standard of care for advanced ovarian cancer, the related post-operative morbidity has not been clearly documented outside pioneering centers. Indeed most of the studies are monocentric with inclusions over several years inducing heterogeneity in techniques and goals of surgery. We assessed the morbidity of optimal cytoreduction surgery for advanced ovarian cancer within a short inclusion period in 6 referral centers dedicated to achieve complete cytoreduction. PATIENTS AND METHODS: The 30 last optimal debulking surgeries of 6 cancer centers were included. Inclusion criteria included: stage IIIc- IV ovarian cancer and optimal surgery performed at the site of inclusion. All post-operative complications within 30 days of surgery were recorded and graded using the Memorial secondary events grading system. Student-t, Chi2 and non-parametric statistical tests were performed. RESULTS: 180 patients were included. There was no demographic differences between the centers. 63 patients underwent surgery including intestinal resections (58 recto-sigmoid resection, 24 diaphragmatic resections, 17 splenectomies. 61 patients presented complications; One patient died post-operatively. Major (grade 3-5 complications requiring subsequent surgeries occurred in 21 patients (11.5%. 76% of patients with a major complication had undergone an ultraradical surgery (P = 0.004. CONCLUSION: While ultraradical surgery may result in complete resection of peritoneal disease in advanced ovarian cancer, the associated complication rate is not negligible. Patients should be carefully evaluated and the timing of their surgery optimized in order to avoid major complications.

  11. The human homologue of unc-93 maps to chromosome 6q27 - characterisation and analysis in sporadic epithelial ovarian cancer

    DEFF Research Database (Denmark)

    Liu, Ying; Dodds, Phillippa; Emilion, Gracy

    2002-01-01

    In sporadic ovarian cancer, we have previously reported allele loss at D6S193 (62%) on chromosome 6q27, which suggested the presence of a putative tumour suppressor gene. Based on our data and that from another group, the minimal region of allele loss was between D6S264 and D6S149 (7.4 cM). To id...

  12. Insights into the field carcinogenesis of ovarian cancer based on the nanocytology of endocervical and endometrial epithelial cells

    OpenAIRE

    Damania, Dhwanil; Roy, Hemant K.; Kunte, Dhananja; Hurteau, Jean A.; Subramanian, Hariharan; Cherkezyan, Lusik; Krosnjar, Nela; Shah, Maitri; Backman, Vadim

    2013-01-01

    Ovarian cancer ranks fifth in cancer fatalities among American women. Although curable at early stages with surgery, most women are diagnosed with symptoms of late-stage metastatic disease. Moreover, none of the current diagnostic techniques are clinically recommended for at-risk women as they preferentially target low-grade tumors (which do not affect longevity) and fail to capture early signatures of more lethal serous tumors which originate in the fimbrae region of the fallopian tubes. Hen...

  13. THE ABERRANT PROMOTER HYPERMETHYLATION PATTERN OF THE ANTI - ANGIOGENIC TSP1 GENE IN EPITHELIAL OVARIAN CARCINOMA: AN INDIAN STUDY

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    Ramesh

    2015-06-01

    Full Text Available PURPOSE: The promoter hypermethylation patterns of Thrombospodin - 1 gene in 50 EOC patients were studied and the methylation pattern was correlated with various clinic pathological parameters. METHODS: The promoter hypermethylation pattern of the TSP - 1 gene was assessed using nested PCR and Methylation specific PCR. STATISTICAL ANALYSIS: All the available data was statistically analyzed using the Chi square test or Fisher Exact Test on the SPSS software version 22.0 and a value <0.0 5 was considered statistically significant. RESULTS: Forty of the fifty ovarian carcinoma samples reported positive for methylation corresponding to a methylation frequency of 80%. A methylation frequency of 89.2%, 83.3% and 42.8% was observed in malignant , Low malignant potential (borderline and benign sample cohorts. CONCLUSION: From the results drawn from this study, it clearly shows that the anti angiogenic protein TSP - 1 is extensively hypermethylated in ovarian carcinoma and that it accumulates over t he progression of the disease from benign to malignant. As previous reports suggest that there is no evidence of mutation of this gene, promoter hypermethylation may be a crucial factor for the down regulation of the gene. Further by clubbing together the promoter hypermethylation pattern of TSP - 1 gene with hypermethylation patterns of other TSG may provide a better insight into the application of using methylation profiles of TSG as a biomarker in the detection of ovarian carcinoma.

  14. LONG-TERM SURVIVAL IN OVARIAN-CANCER - MATURE DATA FROM THE NETHERLANDS JOINT STUDY-GROUP FOR OVARIAN-CANCER

    NARCIS (Netherlands)

    NEIJT, JP; HUININK, WWT; VANDERBURG, MEL; VANOOSTEROM, AT; WILLEMSE, PHB; VERMORKEN, JB; VANLINDERT, ACM; HEINTZ, APM; AARTSEN, E; VANLENT, M; TRIMBOS, JB; DEMEIJER, AJ

    1991-01-01

    In two studies initiated in 1979 and 1981, 377 patients were treated for advanced epithelial ovarian cancer. In the first study patients were randomly assigned to receive Hexa-CAF (hexamethylmelamine, cyclophosphamide, methotrexate, 5-fluorouracil) or CHAP-5 (cyclophosphamide, hexamethylmelamine, do

  15. Oxidatively Modified Proteins in the Serous Subtype of Ovarian Carcinoma

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    Sharifeh Mehrabi

    2014-01-01

    Full Text Available Serous subtype of ovarian cancer is considered to originate from fallopian epithelium mucosa that has been exposed to physiological changes resulting from ovulation. Ovulation influences an increased in inflammation of epithelial ovarian cells as results of constant exposure of cells to ROS. The imbalance between ROS and antioxidant capacities, as well as a disruption of redox signaling, causes a wide range of damage to DNA, proteins, and lipids. This study applied spectrophotometric, dinitrophenylhydrazone (DNPH assay, two-dimensional gel electrophoresis, and Western blot analyses to assess the levels of oxidatively modified proteins in 100 primary serous epithelial ovarian carcinoma and normal/surrounding tissues. These samples were obtained from 56 Caucasian and 44 African-American patients within the age range of 61±10 years. Analyses showed that the levels of reactive protein carbonyl groups increased as stages progressed to malignancy. Additionally, the levels of protein carbonyls in serous ovarian carcinoma among African Americans are 40% (P<0.05 higher relative to Caucasian at similar advanced stages. Results suggest that oxidative stress is involved in the modification of carbonyl protein groups, leading to increased aggressiveness of epithelial ovarian tumors and may contribute to the disease's invasiveness among African Americans.

  16. Successful analysis of anticancer drug sensitivity by CD-DST using pleural fluid and ascites from patients with advanced ovarian cancer: case reports.

    Science.gov (United States)

    Kawaguchi, Makiko; Banno, Kouji; Susumu, Nobuyuki; Yanokura, Megumi; Kuwabara, Yoshiko; Hirao, Nobumaru; Tsukazaki, Katsumi; Nozawa, Shiro

    2005-01-01

    In vitro anticancer drug sensitivity tests have been performed for various types of cancers, and a relationship with clinical response has been observed. The collagen gel droplet-embedded culture drug sensitivity test (CD-DST) is a new in vitro anticancer drug sensitivity test by Yabushita et al., recently reported to be useful in ovarian cancer. CD-DST allows analysis of a small number of cells, compared to other anticancer drug sensitivity tests. Here, we report a successful analysis of anticancer drug sensitivity by CD-DST using cancerous ascites and pleural fluid samples from 2 patients with advanced ovarian cancer. To our knowledge, this is only the second report of the application of CD-DST in ovarian cancer, and our results suggest that CD-DST could be helpful in the selection of anticancer drugs for neoadjuvant chemotherapy in advanced ovarian cancer.

  17. Differences in Regional Diagnostic Strategies and in Intended Versus Actual First-Line Treatment of Patients With Advanced Ovarian Cancer in Denmark

    DEFF Research Database (Denmark)

    Fagö-Olsen, Carsten Lindberg; Ottesen, Bent; Kehlet, Henrik

    2014-01-01

    BACKGROUND: Triage of patients with ovarian cancer to primary debulking surgery (PDS) or neoadjuvant chemotherapy (NACT) is challenging. In Denmark, the use of NACT has increased, but substantial differences in the use of NACT or PDS exist among centers. We aimed to characterize the differences b......-line treatments as well as in the diagnostic process and use of NACT, calling for further discussion on diagnostic strategy and therapeutically approach for patients with advanced ovarian cancer....

  18. CYP1B1 enhances the resistance of epithelial ovarian cancer cells to paclitaxel in vivo and in vitro

    OpenAIRE

    ZHU, ZHUANGYAN; MU, YAQIN; QI, CAIXIA; WANG, JIAN; XI, GUOPING; GUO, JUNCHENG; Mi, Ruoran; ZHAO, FUXI

    2014-01-01

    Ovarian cancer (OC) is the most frequent cause of mortality among gynecological malignancies, with a 5-year survival rate of approximately 30%. The standard regimen for OC therapy includes a platinum agent combined with a taxane, to which the patients frequently acquire resistance. Resistance arises from the oxidation of anticancer drugs by CYP1B1, a cytochrome P450 enzyme overexpressed in malignant OC. The aim of the present study was to determine the role of CYP1B1 expression in the drug re...

  19. A Synthetic Lethality Screen Using a Focused siRNA Library to Identify Sensitizers to Dasatinib Therapy for the Treatment of Epithelial Ovarian Cancer.

    Directory of Open Access Journals (Sweden)

    Harsh B Pathak

    Full Text Available Molecular targeted therapies have been the focus of recent clinical trials for the treatment of patients with recurrent epithelial ovarian cancer (EOC. The majority have not fared well as monotherapies for improving survival of these patients. Poor bioavailability, lack of predictive biomarkers, and the presence of multiple survival pathways can all diminish the success of a targeted agent. Dasatinib is a tyrosine kinase inhibitor of the Src-family kinases (SFK and in preclinical studies shown to have substantial activity in EOC. However, when evaluated in a phase 2 clinical trial for patients with recurrent or persistent EOC, it was found to have minimal activity. We hypothesized that synthetic lethality screens performed using a cogently designed siRNA library would identify second-site molecular targets that could synergize with SFK inhibition and improve dasatinib efficacy. Using a systematic approach, we performed primary siRNA screening using a library focused on 638 genes corresponding to a network centered on EGFR, HER2, and the SFK-scaffolding proteins BCAR1, NEDD9, and EFS to screen EOC cells in combination with dasatinib. We followed up with validation studies including deconvolution screening, quantitative PCR to confirm effective gene silencing, correlation of gene expression with dasatinib sensitivity, and assessment of the clinical relevance of hits using TCGA ovarian cancer data. A refined list of five candidates (CSNK2A1, DAG1, GRB2, PRKCE, and VAV1 was identified as showing the greatest potential for improving sensitivity to dasatinib in EOC. Of these, CSNK2A1, which codes for the catalytic alpha subunit of protein kinase CK2, was selected for additional evaluation. Synergistic activity of the clinically relevant inhibitor of CK2, CX-4945, with dasatinib in reducing cell proliferation and increasing apoptosis was observed across multiple EOC cell lines. This overall approach to improving drug efficacy can be applied to other

  20. The tumour suppressor SOX11 is associated with improved survival among high grade epithelial ovarian cancers and is regulated by reversible promoter methylation

    LENUS (Irish Health Repository)

    Sernbo, Sandra

    2011-09-24

    Abstract Background The neural transcription factor SOX11 has been described as a prognostic marker in epithelial ovarian cancers (EOC), however its role in individual histological subtypes and tumour grade requires further clarification. Furthermore, methylation-dependent silencing of SOX11 has been reported for B cell lymphomas and indicates that epigenetic drugs may be used to re-express this tumour suppressor, but information on SOX11 promoter methylation in EOC is still lacking. Methods SOX11 expression and clinicopathological data was compared using χ2 test in a cohort of 154 cases of primary invasive EOC. Kaplan-Meier analysis and the log rank test were applied to evaluate ovarian cancer-specific survival (OCSS) and overall survival (OS) in strata, according to SOX11 expression. Also, the methylation status of the SOX11 promoter was determined by sodium bisulfite sequencing and methylation specific PCR (MSP). Furthermore, the effect of ectopic overexpression of SOX11 on proliferation was studied through [3H]-thymidine incorporation. Results SOX11 expression was associated with an improved survival of patients with high grade EOC, although not independent of stage. Further analyses of EOC cell lines showed that SOX11 mRNA and protein were expressed in two of five cell lines, correlating with promoter methylation status. Demethylation was successfully performed using 5\\'-Aza-2\\'deoxycytidine (5-Aza-dC) resulting in SOX11 mRNA and protein expression in a previously negative EOC cell line. Furthermore, overexpression of SOX11 in EOC cell lines confirmed the growth regulatory role of SOX11. Conclusions SOX11 is a functionally associated protein in EOC with prognostic value for high-grade tumours. Re-expression of SOX11 in EOC indicates a potential use of epigenetic drugs to affect cellular growth in SOX11-negative tumours.

  1. Acrylamide and glycidamide hemoglobin adducts and epithelial ovarian cancer: a nested case-control study in non-smoking postmenopausal women from the EPIC cohort

    Science.gov (United States)

    Obón-Santacana, Mireia; Lujan-Barroso, Leila; Travis, Ruth C.; Freisling, Heinz; Ferrari, Pietro; Severi, Gianluca; Baglietto, Laura; Boutron-Ruault, Marie-Christine; Fortner, Renée T.; Ose, Jennifer; Boeing, Heiner; Menéndez, Virginia; Sánchez-Cantalejo, Emilio; Chamosa, Saioa; Huerta Castaño, José María; Ardanaz, Eva; Khaw, Kay-Tee; Wareham, Nick; Merritt, Melissa A.; Gunter, Marc J.; Trichopoulou, Antonia; Papatesta, Eleni-Maria; Klinaki, Eleni; Saieva, Calogero; Tagliabue, Giovanna; Tumino, Rosario; Sacerdote, Carlotta; Mattiello, Amalia; Bueno-de-Mesquita, H.B.; Peeters, Petra H.; Onland-Moret, N. Charlotte; Idahl, Annika; Lundin, Eva; Weiderpass, Elisabete; Vesper, Hubert W.; Riboli, Elio; Duell, Eric J

    2015-01-01

    Background Acrylamide was classified as ‘probably carcinogenic to humans (group 2A)’ by the International Agency for Research on Cancer. Epithelial ovarian cancer (EOC) is the fourth cause of cancer mortality in women. Five epidemiological studies have evaluated the association between EOC risk and dietary acrylamide intake assessed using food frequency questionnaires, and one nested case-control study evaluated hemoglobin adducts of acrylamide (HbAA) and its metabolite glycidamide (HbGA) and EOC risk; the results of these studies were inconsistent. Methods A nested case-control study in non-smoking postmenopausal women (334 cases, 417 controls) was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Unconditional logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association between HbAA, HbGA, HbAA+HbGA, and HbGA/HbAA and EOC and invasive serous EOC risk. Results No overall associations were observed between biomarkers of acrylamide exposure analyzed in quintiles and EOC risk; however, positive associations were observed between some middle quintiles of HbGA and HbAA+HbGA. Elevated but non-statistically significant ORs for serous EOC were observed for HbGA and HbAA+HbGA (ORQ5vsQ1:1.91, 95%CI:0.96-3.81 and ORQ5vsQ1:1.90, 95%CI:0.94-3.83, respectively); however, no linear dose-response trends were observed. Conclusion This EPIC nested case-control study failed to observe a clear association between biomarkers of acrylamide exposure and the risk of EOC or invasive serous EOC. Impact It is unlikely that dietary acrylamide exposure increases ovarian cancer risk; however, additional studies with larger sample size should be performed to exclude any possible association with EOC risk. PMID:26376083

  2. Standardized FDG uptake as a prognostic variable and as a predictor of incomplete cytoreduction in primary advanced ovarian cancer

    DEFF Research Database (Denmark)

    Risum, Signe; Jakobsen, Annika Loft; Høgdall, Claus;

    2011-01-01

    Abstract Introduction. In patients with advanced ovarian cancer undergoing preoperative PET/CT, we investigated the prognostic value of SUV in the primary tumor and we evaluated the value of SUV for predicting incomplete primary cytoreduction (macroscopic residual tumor). Material and methods. From...... 15, 2009) the association between SUV and overall survival/cytoreductive result were analyzed in 60 ovarian cancer patients (58 stage III and two stage IV). Results. At inclusion median age was 62 years (range 35-85 years); 97% (58/60) had a performance status =2; 42% (25/60) underwent complete...... debulking (no macroscopic residual tumor); median SUV(max) was 13.5 (range 2.5-39.0). Median follow-up was 30.2 months. At follow-up 57% (34/60) were alive and 43% (26/60) had died from ovarian cancer. SUV(max) in patients alive was not statistically different from SUV(max) in dead patients (p=0...

  3. A phase 2 study of the cytotoxic immunoconjugate CMB-401 (hCTM01-calicheamicin) in patients with platinum-sensitive recurrent epithelial ovarian carcinoma.

    Science.gov (United States)

    Chan, Stephen Y; Gordon, Alan N; Coleman, Robert E; Hall, James B; Berger, Mark S; Sherman, Matthew L; Eten, Catharine B; Finkler, Neil J

    2003-04-01

    The compound CMB-401 is an immunoconjugate consisting of the monoclonal antibody (MAb) hCTM01 directed against polymorphic epithelial mucin covalently bound to the cytotoxic antibiotic calicheamicin by an amide linker. We evaluated CMB-401 as monotherapy for the treatment of recurrent platinum-sensitive epithelial ovarian carcinoma (EOC). Twenty-one 21 women aged 38 to 80 years with recurrent EOC (recurrence >6 months after initial platinum-containing chemotherapy) were enrolled. Tumor response and serum cancer antigen 125 (CA125) levels were assessed before and after active treatment. After an initial intravenous (i.v.) dose of hCTM01 (without calicheamicin), the calicheamicin-linked CMB-401 (16 mg/m(2 ) i.v.) was administered over 60 min for up to 7 cycles, with 4 weeks between cycles. Nineteen patients were evaluable. Measurable changes observed following administration of CMB-401 did not meet the criteria for partial remission (PR). CMB-401 was not effective as monotherapy for this type of EOC. Adverse events experienced by patients in the study included nausea (95%), asthenia (90%), abdominal pain (62%), headache (57%), anorexia (57%), and diarrhea (57%), mostly at a toxicity grade level of 1 or 2. Based on published efficacy of conjugates that deliver calicheamicin via hybrid (bifunctional) linkers [e.g. gemtuzumab ozogamicin (Mylotarg) in acute myeloid leukemia], we hypothesize that the amide linker used in CMB-401 may have contributed to its failure to induce PR in patients in this study. Use of hybrid linkers to target hCTM01 or other antibodies to EOC may warrant further investigation.

  4. Intrauterine device--associated pelvic actinomycosis: a rare disease mimicking advanced ovarian cancer: a case report.

    Science.gov (United States)

    Kirova, Y M; Feuilhade, F; Belda-Lefrère, M A; Le Bourgeois, J P

    1997-01-01

    A case report of intrauterine device (IUD)-associated tubo-ovarian actinomycosis is presented. The patient was a 37-year-old nulliparous woman with IUD usage for the last four years. She presented anemia and weight lost of 8 kg. Ultrasound and computed tomography showed an unilateral large mass in the right adnexum adherent to the uterus and compressing the urinary bladder. Preoperative diagnosis of ovarian cancer with liver metastases was made. Bilateral salpingoophorectomy and total abdominal hysterectomy were performed. After pathological and biological analyses, actinomycosis was diagnosed and the patient was treated postoperatively with penicillin. The purpose of this article is to add to the literature a new case of this rare disease which clinically mimics ovarian cancer.

  5. Outcomes analysis of an alternative formulation of PEGylated liposomal doxorubicin in recurrent epithelial ovarian carcinoma during the drug shortage era [Corrigendum

    Directory of Open Access Journals (Sweden)

    Berger JL

    2015-03-01

    Full Text Available Berger JL, Smith A, Zorn KK, et al. Onco Targets Ther. 2014;7:1409–1413.It has been brought to our attention that there are two pharmaceutical companies that market drugs with the name ‘lipodox’ and we erroneously refer to the product used in our current study-Outcomes analysis of an alternative formulation of PEGylated liposomal doxorubicin in recurrent epithelial ovarian carcinoma during the drug shortage era. by the trade name Lipo-dox®, a drug produced by TTY Biopharm Co. Ltd, when the Sun Pharma product is Lipodox. Lipo-Dox® utilizes a different liposomal particle than Doxil®, DSCP versus HSCP. Due to the similarity of the drug names, we were under the mistaken impression that Sun Pharma’s Lipodox utilized the DSCP liposome. We postulated that this might be related to the poor clinical outcomes seen in our population. It is now clear that Lipodox utilizes the same liposome as Doxil® and this is not a relevant point of discussion. The authors would like to let the readers know that Lipodox uses HSCP as the liposome and this should be corrected in the manuscript. The patients in our current study were all treated with Lipodox, and this drug uses HSCP as the liposome.

  6. Efficient lysis of epithelial ovarian cancer cells by MAGE-A3-induced cytotoxic T lymphocytes using rAAV-6 capsid mutant vector.

    Science.gov (United States)

    Batchu, Ramesh B; Gruzdyn, Oksana V; Moreno-Bost, Amberly M; Szmania, Susann; Jayandharan, Giridhararao; Srivastava, Arun; Kolli, Bala K; Weaver, Donald W; van Rhee, Frits; Gruber, Scott A

    2014-02-12

    MAGE-A3 is highly expressed in epithelial ovarian cancer (EOC), making it a promising candidate for immunotherapy. We investigated whether dendritic cells (DCs) transduced with a rAAV-6 capsid mutant vector Y445F could elicit effective MAGE-A3-specific anti-tumor cytotoxic T lymphocyte (CTL) responses in vitro. MAGE-A3 was cloned and rAAV-6-MAGE-A3 purified, followed by proviral genome detection using real-time PCR. Immunofluorescence detection of rAAV-6-Y445F-MAGE-A3-transduced DCs demonstrated 60% transduction efficiency. Fluorescent in situ hybridization analysis confirmed chromosomal integration of rAAV vectors. Flow cytometric analysis of transduced DCs showed unaltered expression of critical monocyte-derived surface molecules with retention of allo-stimulatory activity. Co-culture of autologous T lymphocytes with MAGE-A3-expressing DCs produced CTLs that secreted IFN-γ, and efficiently killed MAGE-A3+ EOC cells. This form of rAAV-based DC immunotherapy, either alone or more likely in combination with other immune-enhancing protocols, may prove useful in the clinical setting for management of EOC.

  7. Neutrophil to lymphocyte ratio and platelet to lymphocyte ratio are predictive of chemotherapeutic response and prognosis in epithelial ovarian cancer patients treated with platinum-based chemotherapy.

    Science.gov (United States)

    Miao, Yi; Yan, Qin; Li, Shuangdi; Li, Bilan; Feng, Youji

    2016-06-07

    The aim of present study was to investigate the role of preoperative neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) used as prognostic markers for predicting chemotherapeutic response and survival outcomes in patients with epithelial ovarian cancer (EOC) who are receiving platinum-based chemotherapy. A total of 344 patients diagnosed with EOC who are receiving platinum-based chemotherapy from 2005 to 2010 in the hospital were enrolled. NLR and PLR were calculated from complete blood cell count taken before operation. The patients were divided into platinum-resistant (P-R) group and platinum-sensitive (P-S) group according to chemotherapeutic response. Clinicopathologic variables and outcomes were retrospectively collected and compared among groups. We used receiver operating characteristic (ROC) curves to calculate optimal cut-off values for NLR and PLR to predict chemotherapeutic response and prognosis. The AUC, sensitivity, specificity of NLR > 3.02 to predict platinum resistance were 0.819, 75.0% and 81.45%, respectively. The corresponding values of PLR > 207 were 0.727, 60.42% and 85.48%, respectively. Patients with lower value of NLR (NLR platinum resistance in patients with EOC.

  8. Differential cellular responses induced by dorsomorphin and LDN-193189 in chemotherapy-sensitive and chemotherapy-resistant human epithelial ovarian cancer cells.

    Science.gov (United States)

    Ali, Jennifer L; Lagasse, Brittany J; Minuk, Ainsley J; Love, Allison J; Moraya, Amani I; Lam, Linda; Arthur, Gilbert; Gibson, Spencer B; Morrison, Ludivine Coudière; Werbowetski-Ogilvie, Tamra E; Fu, Yangxin; Nachtigal, Mark W

    2015-03-01

    Inherent or acquired drug resistance is a major contributor to epithelial ovarian cancer (EOC) mortality. Novel drugs or drug combinations that produce EOC cell death or resensitize drug resistant cells to standard chemotherapy may improve patient treatment. After conducting drug tolerability studies for the multikinase inhibitors dorsomorphin (DM) and it is structural analogue LDN-193189 (LDN), these drugs were tested in a mouse intraperitoneal xenograft model of EOC. DM significantly increased survival, whereas LDN showed a trend toward increased survival. In vitro experiments using cisplatin (CP)-resistant EOC cell lines, A2780-cp or SKOV3, we determined that pretreatment or cotreatment with DM or LDN resensitized cells to the killing effect of CP or carboplatin (CB). DM was capable of blocking EOC cell cycle and migration, whereas LDN produced a less pronounced effect on cell cycle and no effect on migration. Subsequent analyses using primary human EOC cell samples or additional established EOC cells lines showed that DM or LDN induced a dose-dependent autophagic or cell death response, respectively. DM induced a characteristic morphological change with the appearance of numerous LC3B-containing acidic vacuoles and an increase in LC3BII levels. This was coincident with a decrease in cell growth and the altered cell cycle consistent with DM-induced cytostasis. By contrast, LDN produced a caspase 3-independent, reactive oxygen species-dependent cell death. Overall, DM and LDN possess drug characteristics suitable for adjuvant agents used to treat chemotherapy-sensitive and -resistant EOC.

  9. Vasohibin-1 expression inhibits advancement of ovarian cancer producing various angiogenic factors.

    Science.gov (United States)

    Takahashi, Yoshifumi; Saga, Yasushi; Koyanagi, Takahiro; Takei, Yuji; Machida, Shizuo; Taneichi, Akiyo; Mizukami, Hiroaki; Sato, Yasufumi; Matsubara, Shigeki; Fujiwara, Hiroyuki

    2016-05-01

    Vasohibin-1 (VASH1) is a negative feedback regulator of angiogenesis, the first to be discovered, and was identified in vascular endothelial growth factor (VEGF)-stimulated vascular endothelial cells. Vasohibin-1 inhibits abnormal vascularization induced by various angiogenic factors including fibroblast growth factor and platelet-derived growth factor (PDGF), in addition to VEGF. By focusing on this characteristic of VASH1, we investigated the antitumor effects of VASH1 expression on ovarian cancer cells that produce different angiogenic factors. By using a high VEGF-producing ovarian cancer cell line, SHIN-3, and a high PDGF-producing ovarian cancer cell line, KOC-2S, the cells were transfected with either a VEGF antagonist, soluble VEGF receptor-1 (sVEGFR-1, or sFlt-1), or VASH1 genes to establish their respective cellular expression. The characteristics of these transfectants were compared with controls. We previously reported that the expression of sFlt-1 inhibited tumor vascularization and growth of high VEGF-producing ovarian cancer cells, reduced peritoneal dissemination and ascites development, and prolonged the survival time of the host. However, in the current study, the expression of sFlt-1 had no such effect on the high PDGF-producing ovarian cancer cells used here, whereas VASH1 expression inhibited tumor vascularization and growth, not only in high VEGF-producing cells, but also in high PDGF-producing cells, reduced their peritoneal dissemination and ascites, and prolonged the survival time of the host. These results suggest that VASH1 is an effective treatment for ovarian cancer cells that produce different angiogenic factors.

  10. Chemotherapy Toxicity On Quality of Life in Older Patients With Stage I, Stage II, Stage III, or Stage IV Ovarian Epithelial, Primary Peritoneal Cavity, or Fallopian Tube Cancer

    Science.gov (United States)

    2016-02-09

    Stage I Ovarian Cancer; Stage IA Fallopian Tube Cancer; Stage IB Fallopian Tube Cancer; Stage IC Fallopian Tube Cancer; Stage II Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIB Fallopian Tube Cancer; Stage IIC Fallopian Tube Cancer; Stage III Ovarian Cancer; Stage III Primary Peritoneal Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIC Fallopian Tube Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer

  11. HE4 Gene Overexpression in Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    A Shahi

    2016-03-01

    Full Text Available Introduction: Ovarian cancer is one of the common malignancies within women and the fifth cause of cancer death in women all over the world. Recent developments in Genomics and Proteomics technologies have led to the identification of unknown candidate markers for the diagnosis of ovarian cancer. Human epididymis protein 4 (HE4 has recently been supported to monitor the recurrence or the progression of epithelial ovarian cancer. Therefore, this study aimed to measure the expression of HE4 in women suffering from ovarian cancer. Methods: In this study, 20 paraffin-embedded tissue samples from women with ovarian cancer and 10 normal samples were collected from Imam Khomeini Hospital in Tehran. After removing paraffin, RNA extraction was performed with RNAPlus solution. cDNA was synthesized through reverse transcription by MMULV enzyme. Gene expression was measured by Relative Real time PCR method. Glyceraldehyde phosphate dehydrogenase gene (GAPDH was used as an internal control. Results: The HE4 was expressed in normal and cancerous tissues, though its expression was observed more in tumor tissues (4.083 than noncancerous tissues. The study results also revealed that the expression level of HE4 increased with the advancement of the disease. Conclusion: According to the results, it can be concluded that HE4 expression levels greatly increases in tumor samples. Therefore, HE4 gene expression measurements can serve as a valuable prognostic factor for early detection and treatment management of the disease.

  12. Dysregulation of mitotic machinery genes precedes genome instability during spontaneous pre-malignant transformation of mouse ovarian surface epithelial cells

    Directory of Open Access Journals (Sweden)

    Ulises Urzúa

    2016-10-01

    Full Text Available Abstract Background Based in epidemiological evidence, repetitive ovulation has been proposed to play a role in the origin of ovarian cancer by inducing an aberrant wound rupture-repair process of the ovarian surface epithelium (OSE. Accordingly, long term cultures of isolated OSE cells undergo in vitro spontaneous transformation thus developing tumorigenic capacity upon extensive subcultivation. In this work, C57BL/6 mouse OSE (MOSE cells were cultured up to passage 28 and their RNA and DNA copy number profiles obtained at passages 2, 5, 7, 10, 14, 18, 23, 25 and 28 by means of DNA microarrays. Gene ontology, pathway and network analyses were focused in passages earlier than 20, which is a hallmark of malignancy in this model. Results At passage 14, 101 genes were up-regulated in absence of significant DNA copy number changes. Among these, the top-3 enriched functions (>30 fold, adj p < 0.05 comprised 7 genes coding for centralspindlin, chromosome passenger and minichromosome maintenance protein complexes. The genes Ccnb1 (Cyclin B1, Birc5 (Survivin, Nusap1 and Kif23 were the most recurrent in over a dozen GO terms related to the mitotic process. On the other hand, Pten plus the large non-coding RNAs Malat1 and Neat1 were among the 80 down-regulated genes with mRNA processing, nuclear bodies, ER-stress response and tumor suppression as relevant terms. Interestingly, the earliest discrete segmental aneuploidies arose by passage 18 in chromosomes 7, 10, 11, 13, 15, 17 and 19. By passage 23, when MOSE cells express the malignant phenotype, the dysregulated gene expression repertoire expanded, DNA imbalances enlarged in size and covered additional loci. Conclusion Prior to early aneuploidies, overexpression of genes coding for the mitotic apparatus in passage-14 pre-malignant MOSE cells indicate an increased proliferation rate suggestive of replicative stress. Concomitant down-regulation of nuclear bodies and RNA processing related genes

  13. Centralized treatment of advanced stages of ovarian cancer improves survival: a nationwide Danish survey

    DEFF Research Database (Denmark)

    Fagö-Olsen, Carsten L; Høgdall, Claus; Kehlet, Henrik;

    2011-01-01

    Objective. This retrospective, nationwide, observational study was designed to compare treatment in tertiary referral centers vs. regional hospitals on overall survival for patients with stage IIIC and IV ovarian cancer. Material and methods. The study took place in all gynecological departments ...

  14. Expression of Multidrug Resistance-Associated Markers, Their Relation to Quantitative Pathologic Tumour Characteristics and Prognosis in Advanced Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Mariël Brinkhuis

    2002-01-01

    Full Text Available Mean nuclear area has been consistently shown by different researchers to be a strong and independent prognostic factor in advanced ovarian carcinoma. However, the biological background of the prognostic value of nuclear area remains unclear. Others have found that the multidrug‐resistance (MDR related protein LRP has strong prognostic value. In the present study we have analysed whether the mean nuclear area and LRP are related in tumour tissue of the ovary obtained at the debulking operation before the administration of chemotherapy in 40 patients. The mitotic activity index, volume percentage epithelium, standard deviation of nuclear area and the other MDR‐related proteins P‐glycoprotein (JSB‐1, MRK‐16 and MRP have been investigated additionally for correlations and prognostic value. No correlations were found between the morphometrical features and MDR‐related proteins. Mean nuclear area tended to be larger in LRP positive tumours, but the correlation was not significant. In multivariate analysis LRP‐protein expression and mean nuclear area had independent prognostic value. Further studies are required to elucidate the biological background of the strong prognostic value of mean nuclear area in advanced ovarian cancer.

  15. BCAT1 expression associates with ovarian cancer progression: possible implications in altered disease metabolism.

    Science.gov (United States)

    Wang, Zhi-Qiang; Faddaoui, Adnen; Bachvarova, Magdalena; Plante, Marie; Gregoire, Jean; Renaud, Marie-Claude; Sebastianelli, Alexandra; Guillemette, Chantal; Gobeil, Stéphane; Macdonald, Elizabeth; Vanderhyden, Barbara; Bachvarov, Dimcho

    2015-10-13

    Previously, we have identified the branched chain amino-acid transaminase 1 (BCAT1) gene as notably hypomethylated in low-malignant potential (LMP) and high-grade (HG) serous epithelial ovarian tumors, compared to normal ovarian tissues. Here we show that BCAT1 is strongly overexpressed in both LMP and HG serous epithelial ovarian tumors, which probably correlates with its hypomethylated status. Knockdown of the BCAT1 expression in epithelial ovarian cancer (EOC) cells led to sharp decrease of cell proliferation, migration and invasion and inhibited cell cycle progression. BCAT1 silencing was associated with the suppression of numerous genes and pathways known previously to be implicated in ovarian tumorigenesis, and the induction of some tumor suppressor genes (TSGs). Moreover, BCAT1 suppression resulted in downregulation of numerous genes implicated in lipid production and protein synthesis, suggesting its important role in controlling EOC metabolism. Further metabolomic analyses were indicative for significant depletion of most amino acids and different phospho- and sphingolipids following BCAT1 knockdown. Finally, BCAT1 suppression led to significantly prolonged survival time in xenograft model of advanced peritoneal EOC. Taken together, our findings provide new insights about the functional role of BCAT1 in ovarian carcinogenesis and identify this transaminase as a novel EOC biomarker and putative EOC therapeutic target.

  16. Germline mutation in BRCA1 or BRCA2 and ten-year survival for women diagnosed with epithelial ovarian cancer

    DEFF Research Database (Denmark)

    Candido-dos-Reis, Francisco J; Song, Honglin; Goode, Ellen L

    2015-01-01

    ,314 patients from previously reported studies. All participants had been screened for deleterious germline mutations in BRCA1 and BRCA2. Survival time was analyzed for the combined data using Cox proportional hazard models with BRCA1 and BRCA2 as time-varying covariates. Competing risks were analyzed using......PURPOSE: To analyze the effect of germline mutations in BRCA1 and BRCA2 on mortality in patients with ovarian cancer up to 10 years after diagnosis. EXPERIMENTAL DESIGN: We used unpublished survival time data for 2,242 patients from two case-control studies and extended survival time data for 4...... Fine and Gray model. RESULTS: The combined 10-year overall survival rate was 30% [95% confidence interval (CI), 28%-31%] for non-carriers, 25% (95% CI, 22%-28%) for BRCA1 carriers, and 35% (95% CI, 30%-41%) for BRCA2 carriers. The HR for BRCA1 was 0.53 at time zero and increased over time becoming...

  17. Low MAD2 expression levels associate with reduced progression-free survival in patients with high-grade serous epithelial ovarian cancer.

    LENUS (Irish Health Repository)

    Furlong, Fiona

    2012-04-01

    Epithelial ovarian cancer (EOC) has an innate susceptibility to become chemoresistant. Up to 30% of patients do not respond to conventional chemotherapy [paclitaxel (Taxol®) in combination with carboplatin] and, of those who have an initial response, many patients relapse. Therefore, an understanding of the molecular mechanisms that regulate cellular chemotherapeutic responses in EOC cells has the potential to impact significantly on patient outcome. The mitotic arrest deficiency protein 2 (MAD2), is a centrally important mediator of the cellular response to paclitaxel. MAD2 immunohistochemical analysis was performed on 82 high-grade serous EOC samples. A multivariate Cox regression analysis of nuclear MAD2 IHC intensity adjusting for stage, tumour grade and optimum surgical debulking revealed that low MAD2 IHC staining intensity was significantly associated with reduced progression-free survival (PFS) (p = 0.0003), with a hazard ratio of 4.689. The in vitro analyses of five ovarian cancer cell lines demonstrated that cells with low MAD2 expression were less sensitive to paclitaxel. Furthermore, paclitaxel-induced activation of the spindle assembly checkpoint (SAC) and apoptotic cell death was abrogated in cells transfected with MAD2 siRNA. In silico analysis identified a miR-433 binding domain in the MAD2 3\\' UTR, which was verified in a series of experiments. Firstly, MAD2 protein expression levels were down-regulated in pre-miR-433 transfected A2780 cells. Secondly, pre-miR-433 suppressed the activity of a reporter construct containing the 3\\'-UTR of MAD2. Thirdly, blocking miR-433 binding to the MAD2 3\\' UTR protected MAD2 from miR-433 induced protein down-regulation. Importantly, reduced MAD2 protein expression in pre-miR-433-transfected A2780 cells rendered these cells less sensitive to paclitaxel. In conclusion, loss of MAD2 protein expression results in increased resistance to paclitaxel in EOC cells. Measuring MAD2 IHC staining intensity may predict

  18. Cost-effectiveness of primary debulking surgery when compared to neoadjuvant chemotherapy in the management of stage III C and IV epithelial ovarian cancer

    Directory of Open Access Journals (Sweden)

    Forde GK

    2016-08-01

    Full Text Available Gareth K Forde,1 Jenny Chang,2 Argyrios Ziogas,21Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Irvine Medical Center, University of California, Orange, CA, USA; 2Department of Epidemiology, University of California, Irvine, CA, USA Objectives: To examine the cost-effectiveness of primary debulking surgery (PDS when compared to neoadjuvant chemotherapy (NACT in the management of epithelial ovarian cancer (EOC using Surveillance, Epidemiology, and End Results data linked to Medicare claims (SEER-Medicare. Methods: Using a Markov model, the cost-effectiveness of PDS was compared to that of NACT. We modeled cost and survival inputs using data from women in the SEER-Medicare database with ovarian cancer treated by either PDS or NACT between 1992 and 2009. Direct and indirect costs were discounted by an annual rate of 3%. Utility weights were obtained from published data. The incremental cost-effectiveness ratio (ICER of PDS compared to NACT was calculated. Results: In our model, women with stage IIIC EOC had a higher mean adjusted treatment cost for PDS when compared to NACT ($31,945 vs $30,016 but yielded greater quality-adjusted life-years (QALYs (1.79 vs 1.69. The ICER was $19,359/QALY gained. Women with stage IV EOC had a higher mean adjusted treatment cost following PDS when compared to NACT ($31,869 vs $27,338 but yielded greater QALYs (1.69 vs 1.66. The ICER was $130,083/QALY gained. A sensitivity analysis showed that for both PDS and NACT the ICER was sensitive to incremental changes in the utility weight. Conclusion: PDS is significantly more cost-effective for women with stage IIIC when compared to NACT. In women with stage IV EOC, PDS is also more cost-effective though the QALYs gained are much more costly and exceed a $50,000 willingness to pay. Keywords: Markov model, gynecologic cancer, chemotherapy, up front surgery

  19. Statin use and risk for ovarian cancer

    DEFF Research Database (Denmark)

    Baandrup, L; Dehlendorff, C; Friis, Søren;

    2015-01-01

    BACKGROUND: Limited data suggest that statin use reduces the risk for ovarian cancer. METHODS: Using Danish nationwide registries, we identified 4103 cases of epithelial ovarian cancer during 2000-2011 and age-matched them to 58,706 risk-set sampled controls. Conditional logistic regression...... was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for epithelial ovarian cancer overall, and for histological types, associated with statin use. RESULTS: We observed a neutral association between ever use of statins and epithelial ovarian cancer risk (OR=0.98, 95% CI=0.......87-1.10), and no apparent risk variation according to duration, intensity or type of statin use. Decreased ORs associated with statin use were seen for mucinous ovarian cancer (ever statin use: OR=0.63, 95% CI=0.39-1.00). CONCLUSIONS: Statin use was not associated with overall risk for epithelial ovarian cancer...

  20. Isolation and Identification of Ovarian Cancer Stem Cells from HumanEpithelial Ovarian Carcinoma Cell Line 3AO%人卵巢肿瘤细胞系3AO中肿瘤干细胞的分离鉴定

    Institute of Scientific and Technical Information of China (English)

    李青; 唐良萏; 汪艳; 张曦; 朱慧芬

    2012-01-01

    Objective To isolate and identify cancer stem cells-like cells(CSC-LCs)from the human epithelial ovarian carcinoma cell line 3AO and define their biological characteristics through accessing the activity of the anti-apoptosis and drug resistance. Methods CD133 cells were isolated from 3AO by immunomagnetic beads(miniMACS). Cell counting was taken to reflect the proliferation ability. The self-renew capacity of CD133+ cells was detected by using flow cytometry(FCM). No more than 10' CD133+ cells were inoculated subcutaneously. Formation of xenografts in nude mice was taken to demonstrate the tu-morigenesis of these cells. MTT assay was also taken to characterize the sensitivity of CD133 cells against chemotherapeutic drug. Results CD133+ cancer stem cells were obtained from the human epithelial ovarian carcinoma cell line 3AO, which could self-renew, proliferate and differentiate to a number of CD133 cells. Tumors transplanted into nude mice showed that the tumor formation rate of CD133+ cells was 10/10 and the average tumor formation time was (58 + 6) days, and in CD133- group, tumor formation rate was 4/10 and the average tumor formation time was (145i8) days,suggesting the tumor formation ability of CD133+ cells was significantly stronger than CD133‐ cells. MTT results revealed that IC5q value of CD133+ was 2. 5 times higher than CD133‐ suggesting that CD133+ cells were not sensitive to cisplatin. Staining of cisplatin-treated cells with acridine orange displayed that a large number of CD133 cells showed apoptotic state, while most of the CD133 represented normal form. Further Annexin V-FITC and PI double staining results showed that CD133+ cells had stronger anti-apoptotic ability than CD133‐ cells after treatment with cisplatin. Conclusion CD133 could be further studied as a molecular marker for identification of ovary cancer stem cells, which also provides the basis for the isolation,culture and identification of cancer stem cells in epithelial ovarian

  1. Expression of the RNA-binding protein RBM3 is associated with a favourable prognosis and cisplatin sensitivity in epithelial ovarian cancer

    LENUS (Irish Health Repository)

    Ehlen, Asa

    2010-08-20

    Abstract Background We recently demonstrated that increased expression of the RNA-binding protein RBM3 is associated with a favourable prognosis in breast cancer. The aim of this study was to examine the prognostic value of RBM3 mRNA and protein expression in epithelial ovarian cancer (EOC) and the cisplatin response upon RBM3 depletion in a cisplatin-sensitive ovarian cancer cell line. Methods RBM3 mRNA expression was analysed in tumors from a cohort of 267 EOC cases (Cohort I) and RBM3 protein expression was analysed using immunohistochemistry (IHC) in an independent cohort of 154 prospectively collected EOC cases (Cohort II). Kaplan Meier analysis and Cox proportional hazards modelling were applied to assess the relationship between RBM3 and recurrence free survival (RFS) and overall survival (OS). Immunoblotting and IHC were used to examine the expression of RBM3 in a cisplatin-resistant ovarian cancer cell line A2780-Cp70 and its cisplatin-responsive parental cell line A2780. The impact of RBM3 on cisplatin response in EOC was assessed using siRNA-mediated silencing of RBM3 in A2780 cells followed by cell viability assay and cell cycle analysis. Results Increased RBM3 mRNA expression was associated with a prolonged RFS (HR = 0.64, 95% CI = 0.47-0.86, p = 0.003) and OS (HR = 0.64, 95% CI = 0.44-0.95, p = 0.024) in Cohort I. Multivariate analysis confirmed that RBM3 mRNA expression was an independent predictor of a prolonged RFS, (HR = 0.61, 95% CI = 0.44-0.84, p = 0.003) and OS (HR = 0.62, 95% CI = 0.41-0.95; p = 0.028) in Cohort I. In Cohort II, RBM3 protein expression was associated with a prolonged OS (HR = 0.53, 95% CI = 0.35-0.79, p = 0.002) confirmed by multivariate analysis (HR = 0.61, 95% CI = 0.40-0.92, p = 0.017). RBM3 mRNA and protein expression levels were significantly higher in the cisplatin sensitive A2780 cell line compared to the cisplatin resistant A2780-Cp70 derivative. siRNA-mediated silencing of RBM3 expression in the A2780 cells resulted

  2. The efficacy and safety of Oxaliplatin-Vinorelbine as a second-line chemotherapy combination in patients with platinum-resistant pretreated epithelial ovarian cancer: A retrospective study

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    Fidia Mumtahana

    2014-12-01

    Full Text Available Purpose: The main purpose of this study was to analyze the effects and tolerability of Oxaliplatin-Vinorelbine combination on Platinum-resistant epithelial ovarian carcinoma (EOC patients.Methods: A single centered retrospective study comprising of 34 patients was conducted, and all 34 patients were treated with Vinorelbine 30 mg/m2 on day 1 and 8 along with Oxaliplatin 100 mg/m2 on day 1 of 3 weeks treatment cycle following progressive platinum-resistant EOC. Results: The combination showed an overall response rate (ORR of 18% (95% CI, 4.4 - 31.6 where 2 (6% patients had complete response and 4 (12% patients had partial response. Stable disease was observed in 9 (26% patients and progressive disease in 19 (56% patients. Median diseases free survival, median relapse free survival and median time to progression was 17.05 months, 4.4 months, and 1.25 months, respectively. Hematological toxicities were mild; only 1 (2.9% patient had G3 anemia and major non-hematological toxicities include nausea-vomiting, diarrhea, constipation, hepatotoxicity, fatigueness and alopecia, which are mainly limited to G1-G2 and reversible. Conclusion: The effect of this combination is moderate as a second line treatment of platinum resistant EOC; however, in comparison with other regimens of Vinorelbine and Oxaliplatin, the activity is substandard but the toxicity profile is well tolerable. Further multicenter evaluation is needed for the better understanding of the therapeutic efficacy of the combination.

  3. Reproductive and hormone-related risk factors for epithelial ovarian cancer by histologic pathways, invasiveness and histologic subtypes: Results from the EPIC cohort.

    Science.gov (United States)

    Fortner, Renée T; Ose, Jennifer; Merritt, Melissa A; Schock, Helena; Tjønneland, Anne; Hansen, Louise; Overvad, Kim; Dossus, Laure; Clavel-Chapelon, Françoise; Baglietto, Laura; Boeing, Heiner; Trichopoulou, Antonia; Benetou, Vassiliki; Lagiou, Pagona; Agnoli, Claudia; Mattiello, Amalia; Masala, Giovanna; Tumino, Rosario; Sacerdote, Carlotta; Bueno-de-Mesquita, H B As; Onland-Moret, N Charlotte; Peeters, Petra H; Weiderpass, Elisabete; Torhild Gram, Inger; Duell, Eric J; Larrañaga, Nerea; Ardanaz, Eva; Sánchez, María-José; Chirlaque, M-D; Brändstedt, Jenny; Idahl, Annika; Lundin, Eva; Khaw, Kay-Tee; Wareham, Nick; Travis, Ruth C; Rinaldi, Sabina; Romieu, Isabelle; Gunter, Marc J; Riboli, Elio; Kaaks, Rudolf

    2015-09-01

    Whether risk factors for epithelial ovarian cancer (EOC) differ by subtype (i.e., dualistic pathway of carcinogenesis, histologic subtype) is not well understood; however, data to date suggest risk factor differences. We examined associations between reproductive and hormone-related risk factors for EOC by subtype in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Among 334,126 women with data on reproductive and hormone-related risk factors (follow-up: 1992-2010), 1,245 incident cases of EOC with known histology and invasiveness were identified. Data on tumor histology, grade, and invasiveness, were available from cancer registries and pathology record review. We observed significant heterogeneity by the dualistic model (i.e., type I [low grade serous or endometrioid, mucinous, clear cell, malignant Brenner] vs. type II [high grade serous or endometrioid]) for full-term pregnancy (phet  = 0.02). Full-term pregnancy was more strongly inversely associated with type I than type II tumors (ever vs. never: type I: relative risk (RR) 0.47 [95% confidence interval (CI): 0.33-0.69]; type II, RR: 0.81 [0.61-1.06]). We observed no significant differences in risk in analyses by major histologic subtypes of invasive EOC (serous, mucinous, endometrioid, clear cell). None of the investigated factors were associated with borderline tumors. Established protective factors, including duration of oral contraceptive use and full term pregnancy, were consistently inversely associated with risk across histologic subtypes (e.g., ever full-term pregnancy: serous, RR: 0.73 [0.58-0.92]; mucinous, RR: 0.53 [0.30-0.95]; endometrioid, RR: 0.65 [0.40-1.06]; clear cell, RR: 0.34 [0.18-0.64]; phet  = 0.16). These results suggest limited heterogeneity between reproductive and hormone-related risk factors and EOC subtypes.

  4. Cediranib, an Oral Inhibitor of Vascular Endothelial Growth Factor Receptor Kinases, Is an Active Drug in Recurrent Epithelial Ovarian, Fallopian Tube, and Peritoneal Cancer

    Science.gov (United States)

    Matulonis, Ursula A.; Berlin, Suzanne; Ivy, Percy; Tyburski, Karin; Krasner, Carolyn; Zarwan, Corrine; Berkenblit, Anna; Campos, Susana; Horowitz, Neil; Cannistra, Stephen A.; Lee, Hang; Lee, Julie; Roche, Maria; Hill, Margaret; Whalen, Christin; Sullivan, Laura; Tran, Chau; Humphreys, Benjamin D.; Penson, Richard T.

    2009-01-01

    Purpose Angiogenesis is important for epithelial ovarian cancer (EOC) growth, and blocking angiogenesis can lead to EOC regression. Cediranib is an oral tyrosine kinase inhibitor (TKI) of vascular endothelial growth factor receptor (VEGFR) -1, VEGFR-2, VEGFR-3, and c-kit. Patients and Methods We conducted a phase II study of cediranib for recurrent EOC or peritoneal or fallopian tube cancer; cediranib was administered as a daily oral dose, and the original dose was 45 mg daily. Because of toxicities observed in the first 11 patients, the dose was lowered to 30 mg. Eligibility included ≤ two lines of chemotherapy for recurrence. End points included response rate (via Response Evaluation Criteria in Solid Tumors [RECIST] or modified Gynecological Cancer Intergroup CA-125), toxicity, progression-free survival (PFS), and overall survival (OS). Results Forty-seven patients were enrolled; 46 were treated. Clinical benefit rate (defined as complete response [CR] or partial response [PR], stable disease [SD] > 16 weeks, or CA-125 nonprogression > 16 weeks), which was the primary end point, was 30%; eight patients (17%; 95% CI, 7.6% to 30.8%) had a PR, six patients (13%; 95% CI, 4.8% to 25.7%) had SD, and there were no CRs. Eleven patients (23%) were removed from study because of toxicities before two cycles. Grade 3 toxicities (> 20% of patients) included hypertension (46%), fatigue (24%), and diarrhea (13%). Grade 2 hypothyroidism occurred in 43% of patients. Grade 4 toxicities included CNS hemorrhage (n = 1), hypertriglyceridemia/hypercholesterolemia/elevated lipase (n = 1), and dehydration/elevated creatinine (n = 1). No bowel perforations or fistulas occurred. Median PFS was 5.2 months, and median OS has not been reached; median follow-up time is 10.7 months. Conclusion Cediranib has activity in recurrent EOC, tubal cancer, and peritoneal cancer with predictable toxicities observed with other TKIs. PMID:19826113

  5. The role of BRCA status on the prognosis of patients with epithelial ovarian cancer: a systematic review of the literature with a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Chaoyang Sun

    Full Text Available OBJECTIVE: The role of BRCA dysfunction on the prognosis of patients with epithelial ovarian cancer (EOCs remains controversial. This systematic review tried to assess the role of BRCA dysfunction, including BRCA1/2 germline, somatic mutations, low BRCA1 protein/mRNA expression or BRCA1 promoter methylation, as prognostic factor in EOCs. METHODS: Studies were selected for analysis if they provided an independent assessment of BRCA status and prognosis in EOC. To make it possible to aggregate survival results of the published studies, their methodology was assessed using a modified quality scale. RESULTS: Of 35 evaluable studies, 23 identified BRCA dysfucntion status as a favourable prognostic factor. No significant differences were detected in the global score of quality assessment. The aggregated hazard ratio (HR of overall survival (OS of 34 evaluable studies suggested that BRCA dysfunction status had a favourable impact on OS (HR = 0.69, 95% CI 0.61-0.79, and when these studies were categorised into BRCA1/2 mutation and low protein/mRNA expression of BRCA1 subgroups, all of them demonstrated positive results (HR = 0.67, 95% CI: 0.57-0.78; HR = 0.62, 95% CI: 0.51-0.75; and HR = 0.51, 95% CI: 0.33-0.78, respectively, except for the subgroup of BRCA1 promoter methylation (HR = 1.59, 95% CI: 0.72-3.50. The meta-analysis of progression-free survival (PFS, which included 18 evaluable studies, demonstrated that BRCA dysfunction status was associated with a longer PFS in EOC (HR = 0.69, 95% CI: 0.63-0.76. CONCLUSIONS: Patients with BRCA dysfunction status tend to have a better outcome, but further prospective clinical studies comparing the different BRCA statuses in EOC is urgently needed to specifically define the most effective treatment for the separate patient groups.

  6. Investigate the Role of Obesity in Ovarian Cancer Initiation and Progression

    Science.gov (United States)

    2016-05-01

    TERMS Obesity, Ovarian Cancer, ovarian stem cells, inflammation, adipose tissue 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18...transformed ovarian epithelial cells in obese animals. The goal is to identify genes and pathways that lead to ovarian cancer initiation and...progression. We also aim to identify secreted factors from adipose tissue that promote ovarian cancer initiation and progression in obesity

  7. Paclitaxel and Carboplatin or Bleomycin Sulfate, Etoposide Phosphate, and Cisplatin in Treating Patients With Advanced or Recurrent Sex Cord-Ovarian Stromal Tumors

    Science.gov (United States)

    2016-03-16

    Ovarian Granulosa Cell Tumor; Ovarian Gynandroblastoma; Ovarian Sertoli-Leydig Cell Tumor; Ovarian Sex Cord Tumor With Annular Tubules; Ovarian Sex Cord-Stromal Tumor; Ovarian Sex Cord-Stromal Tumor of Mixed or Unclassified Cell Types; Ovarian Steroid Cell Tumor

  8. Evaluation of candidate stromal epithelial cross-talk genes identifies association between risk of serous ovarian cancer and TERT, a cancer susceptibility "hot-spot"

    DEFF Research Database (Denmark)

    Johnatty, Sharon E; Beesley, Jonathan; Chen, Xiaoqing;

    2010-01-01

    with ovarian cancer risk in the smaller, five-study replication study (Pper-allele=0.03). Combined analysis of the discovery and replication sets for this TERT SNP showed an increased risk of serous ovarian cancer among non-Hispanic whites [adj. ORper-allele 1.14 (1.04-1.24) p=0.003]. Our study adds...

  9. Current Advances in Epigenetic Modification and Alteration during Mammalian Ovarian Folliculogenesis

    Institute of Scientific and Technical Information of China (English)

    Zengxiang Pan; Jinbi Zhang; Qifa Li; Yinxia Li; Fangxiong Shi; Zhuang Xie; Honglin Liu

    2012-01-01

    During the growth and development of mammalian ovarian follicles,the activation and deactivation of mass genes are under the synergistic control of diverse modifiers through genetic and epigenetic events.Many factors regulate gene activity and functions through epigenetic modification without altering the DNA sequence,and the common mechanisms may include but arc not limited to: DNA methylation,histone modifications (e.g.,acetylation,deacetylation,phosphorylation,methylation,and ubiquitination),and RNA-associated silencing of gene expression by noncoding RNA.Over the past decade,substantial progress has been achieved in studies involving the epigenetic alterations during mammalian germ cell development.A number of candidate regulatory factors have been identified.This review focuses on the current available information of epigenetic alterations (e.g.,DNA methylation,histone modification,noncoding-RNA-mediated regulation) during mammalian folliculogenesis and recounts when and how epigenetic patterns are differentially established,maintained,or altered in this process.Based on different types of epigenetic regulation,our review follows the temporal progression of events during ovarian folliculogenesis and describes the epigenetic changes and their contributions to germ cell—specific functions at each stage (i.e.,primordial folliculogenesis (follicle formation),follicle maturation,and follicular atresia).

  10. Ovarian cancer cell line panel (OCCP: clinical importance of in vitro morphological subtypes.

    Directory of Open Access Journals (Sweden)

    Corine M Beaufort

    Full Text Available Epithelial ovarian cancer is a highly heterogeneous disease and remains the most lethal gynaecological malignancy in the Western world. Therapeutic approaches need to account for inter-patient and intra-tumoural heterogeneity and detailed characterization of in vitro models representing the different histological and molecular ovarian cancer subtypes is critical to enable reliable preclinical testing. There are approximately 100 publicly available ovarian cancer cell lines but their cellular and molecular characteristics are largely undescribed. We have characterized 39 ovarian cancer cell lines under uniform conditions for growth characteristics, mRNA/microRNA expression, exon sequencing, drug response for clinically-relevant therapeutics and collated all available information on the original clinical features and site of origin. We tested for statistical associations between the cellular and molecular features of the lines and clinical features. Of the 39 ovarian cancer cell lines, 14 were assigned as high-grade serous, four serous-type, one low-grade serous and 20 non-serous type. Three morphological subtypes: Epithelial (n = 21, Round (n = 7 and Spindle (n = 12 were identified that showed distinct biological and molecular characteristics, including overexpression of cell movement and migration-associated genes in the Spindle subtype. Comparison with the original clinical data showed association of the spindle-like tumours with metastasis, advanced stage, suboptimal debulking and poor prognosis. In addition, the expression profiles of Spindle, Round and Epithelial morphologies clustered with the previously described C1-stromal, C5-mesenchymal and C4 ovarian subtype expression profiles respectively. Comprehensive profiling of 39 ovarian cancer cell lines under controlled, uniform conditions demonstrates clinically relevant cellular and genomic characteristics. This data provides a rational basis for selecting models to develop

  11. New insights in the pathophysiology of ovarian cancer and implications for screening and prevention.

    Science.gov (United States)

    Nezhat, Farr R; Apostol, Radu; Nezhat, Camran; Pejovic, Tanja

    2015-09-01

    Despite advances in medicine, ovarian cancer remains the deadliest of the gynecological malignancies. Herein we present the latest information on the pathophysiology of ovarian cancer and its significance for ovarian cancer screening and prevention. A new paradigm for ovarian cancer pathogenesis presupposes 2 distinct types of ovarian epithelial carcinoma with distinct molecular profiles: type I and type II carcinomas. Type I tumors include endometrioid, clear-cell carcinoma, and low-grade serous carcinoma and mostly arise via defined sequence either from endometriosis or from borderline serous tumors, mostly presenting in an early stage. More frequent type II carcinomas are usually high-grade serous tumors, and recent evidence suggests that the majority arise from the fimbriated end of the fallopian tube. Subsequently, high-grade serous carcinomas usually present at advanced stages, likely as a consequence of the rapid peritoneal seeding from the open ends of the fallopian tubes. On the other hand, careful clinical evaluation should be performed along with risk stratification and targeted treatment of women with premalignant conditions leading to type I cancers, most notably endometriosis and endometriomas. Although the chance of malignant transformation is low, an understanding of this link offers a possibility of prevention and early intervention. This new evidence explains difficulties in ovarian cancer screening and helps in forming new recommendations for ovarian cancer risk evaluation and prophylactic treatments.

  12. Imaging of peritoneal deposits in ovarian cancer:A pictorial review

    Institute of Scientific and Technical Information of China (English)

    Sheragaru Hanumanthappa Chandrashekhara; Gowramma Sannanaik Triveni; Rahul Kumar

    2016-01-01

    As per incidence, ovarian carcinoma is the second most common gynaecological malignancy in women. In spite of advanced technology, patient awareness and effective screening methods, epithelial ovarian cancer is usually diagnosed at an advanced stage(stage Ⅲ). Surgical debulking of disease is mainstay of improving the patient survival even in advanced stages. Thus exact delineation of cancer spread in the abdominal cavity guides the surgeon prior to the surgery, help them to decide resectability of lesion and plan for further need of other surgical speciality or need of neoadjuvant chemotherapy. Imaging particularly well-planned contrast-enhanced computed tomography answers most of the queries raised by the treating surgeon. The aim of this article is to review the way ovarian carcinoma spread in the peritoneal cavity and to stress the accurate interpretation of cancer deposits on imaging which can help the treating team to reach optimal management of patients.

  13. First-line treatment of advanced ovarian cancer with paclitaxel/carboplatin with or without epirubicin (TEC versus TC)-a gynecologic cancer intergroup study of the NSGO, EORTC GCG and NCIC CTG

    DEFF Research Database (Denmark)

    Lindemann, K.; Christensen, R. D.; Vergote, I.;

    2012-01-01

    phase III study comparing carboplatin plus paclitaxel (TC; area under the curve 5 and 175 mg/m(2)) with the same combination and epirubicin (TEC; 75 mg/m(2) i.v.). Between March 1999 and August 2001, 887 patients with epithelial ovarian, tubal or peritoneal cancer International Federation of Gynecology...

  14. Resveratrol Attenuates the Metastasis of Epithelial Ovarian Carcinoma by Sirt-1%白藜芦醇通过Sirt-1降低卵巢上皮细胞癌侵袭性作用机制的研究

    Institute of Scientific and Technical Information of China (English)

    高慧

    2015-01-01

    Objective To study the effects of resveratrol in ovarian epithelial carcinoma and explore the molecular mechanism. Methods Human ovarian cancer cells was divided into three groups, (A) low metastasis group (B) high me-tastasis group (C) high metastasis group with resveratrol, then extraction protein and RNA respectively,Western blot analy-sis were used to determine the effect of resveratrol on the expression levels of SIRT1, AP-1, and MMP-7 proteins and RT-PCR assay were used to determine the genetic transcription level of MMP-7. Results Western Blot analysis and RT-PCR revealed that the levels of MMP-7 and AP-1 were significantly upregulated in high metastasis ovarian epithelial car-cinoma, however resveratrol attenuated the levels of MMP-7 and AP-1(P<0.05), correspondingly, resveratrol could in-crease the expression of Sirt 1(P<0.05). Conclusion Resveratrol could inhibit metastasis of ovarian epithelial carcinoma mediated by Sirt1 activation.%目的 探讨白藜芦醇对卵巢上皮细胞癌侵袭能力的影响.方法 人卵巢癌细胞分为三组,低转移组,高转移组,高转移+白藜芦醇组,分别提取蛋白和RNA,Western Blot测定MMP-7、Sirt-1、AP-1的蛋白表达水平,RT-PCR测定MMP-7的基因转录水平.结果 白藜芦醇可以明显的激活高转移卵巢上皮细胞癌当中Sirt-1的作用,与高转移组相比,Sirt-1的表达明显增加(P<0.05),白藜芦醇抑制卵巢上皮细胞癌当中AP-1和MMP-7的表达(P<0.05).结论 白藜芦醇具有明显的降低卵巢上皮细胞癌侵袭性的药理作用,这种作用和其上调Sirt-1的表达密切相关.

  15. Evaluation of HE4, CA125, risk of ovarian malignancy algorithm (ROMA) and risk of malignancy index (RMI) as diagnostic tools of epithelial ovarian cancer in patients with a pelvic mass

    DEFF Research Database (Denmark)

    Karlsen, Mona Aarenstrup; Sandhu, Noreen; Høgdall, Claus

    2012-01-01

    Diagnostic factors are needed to improve the currently used serum CA125 and risk of malignancy index (RMI) in differentiating ovarian cancer (OC) from other pelvic masses, thereby achieving precise and fast referral to a tertiary center and correct selection for further diagnostics. The aim was t...... was to evaluate serum Human Epididymis protein 4 (HE4) and the risk of ovarian malignancy algorithm (ROMA) for these purposes....

  16. Overexpression of SnoN/SkiL, amplified at the 3q26.2 locus, in ovarian cancers: A role in ovarian pathogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Nanjundan, Meera; Cheng, Kwai Wa; Zhang, Fan; Lahad, John; Kuo, Wen-Lin; Schmandt, Rosemarie; Smith-McCune, Karen; Fishman, David; Gray, Joe W.; Mills, Gordon B.

    2008-07-18

    High-resolution array comparative genomic hybridization of 235 serous epithelial ovarian cancers demonstrated a regional increase at 3q26.2 encompassing SnoN/SkiL, a coregulator of SMAD/TGF{beta} signaling. SnoN RNA transcripts were elevated in {approx}80% of advanced stage serous epithelial ovarian cancers. In both immortalized normal (TIOSE) and ovarian carcinoma cell lines (OVCA), SnoN RNA levels were increased by TGF{beta} stimulation and altered by LY294002 and JNK II inhibitor treatment suggesting that the PI3K and JNK signaling pathways may regulate TGF{beta}-induced increases in SnoN RNA. In TIOSE, SnoN protein levels were reduced 15min post TGF{beta}-stimulation, likely by proteosome-mediated degradation. In contrast, in OVCA, SnoN levels were elevated 3h post-stimulation potentially as a result of inhibition of the proteosome. To elucidate the role of SnoN in ovarian tumorigenesis, we explored the effects of both increasing and decreasing SnoN levels. In both TIOSE and OVCA, SnoN siRNA decreased cell growth between 20 and 50% concurrent with increased p21 levels. In TIOSE, transient expression of SnoN repressed TGF{beta} induction of PAI-1 promoters with little effect on the p21 promoter or resultant cell growth. In contrast to the effects of transient expression, stable expression of SnoN in TIOSE led to growth arrest through induction of senescence. Collectively, these results implicate SnoN levels in multiple roles during ovarian carcinogenesis: promoting cellular proliferation in ovarian cancer cells and as a positive mediator of cell cycle arrest and senescence in non-transformed ovarian epithelial cells.

  17. Ovarian carcinoma associated with pregnancy: A clinicopathologic analysis of 23 cases and review of the literature

    Directory of Open Access Journals (Sweden)

    Ghaemmaghami Fatemeh

    2008-01-01

    Full Text Available Abstract Background The aim of this study was to analyze and describe cases of ovarian cancer in pregnant women treated at our center and to review the literature concerned, and to discuss the rationale for therapy. Methods Twenty-Three patients of ovarian malignancies during pregnancy were treated at Vali- Asr Hospital between 1991 and 2002. Data on treatment and follow-up were evaluated. Results The incidence of ovarian carcinoma associated with pregnancy in our series was 0.083/1000 deliveries. Eleven (47.8% were found with ovarian malignant germ cell tumors, five (21.7% with low malignant potential tumors, four (17.4% with invasive epithelial tumors, and three (13% with sex cord stromal tumors. Seventeen (73.9% of the patients were diagnosed in stage I and had complete remission. Five of the six in advanced stage died. The mean follow-up was 36.3 months. The prognosis was significantly related with stage and histological type (P Conclusion Early finding of ascitis by ultrasound and persistent large ovarian mass during pregnancy may be related to malignancy and advanced stage. Pregnant women in advanced stage of ovarian cancer seem to have poor prognosis.

  18. Ovarian Cancer

    Science.gov (United States)

    ... deaths than other female reproductive cancers. The sooner ovarian cancer is found and treated, the better your chance for recovery. But ovarian cancer is hard to detect early. Women with ovarian ...

  19. New perspectives on targeted therapy in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Coward JIG

    2015-02-01

    Full Text Available Jermaine IG Coward,1–3 Kathryn Middleton,1 Felicity Murphy1 1Mater Health Services, Raymond Terrace, South Brisbane, QLD, Australia; 2Inflammtion and Cancer Therapeutics Group, Mater Research, University of Queensland, Translational Research Institute, Woolloongabba, Brisbane, QLD, Australia; 3School of Medicine, University of Queensland, Brisbane, QLD, Australia Abstract: Epithelial ovarian cancer remains the most lethal gynecologic malignancy. During the last 15 years, there has been only marginal improvement in 5 year overall survival. These daunting statistics are compounded by the fact that despite all subtypes exhibiting striking heterogeneity, their systemic management remains identical. Although changes to the scheduling and administration of chemotherapy have improved outcomes to a degree, a therapeutic ceiling is being reached with this approach, resulting in a number of trials investigating the efficacy of targeted therapies alongside standard treatment algorithms. Furthermore, there is an urge to develop subtype-specific studies in an attempt to improve outcomes, which currently remain poor. This review summarizes the key studies with antiangiogenic agents, poly(adenosine diphosphate [ADP]-ribose inhibitors, and epidermal growth factor receptor/human epidermal growth factor receptor family targeting, in addition to folate receptor antagonists and insulin growth factor receptor inhibitors. The efficacy of treatment paradigms used in non-ovarian malignancies for type I tumors is also highlighted, in addition to recent advances in appropriate patient stratification for targeted therapies in epithelial ovarian cancer. Keywords: antiangiogenic therapy, high-grade serous, low grade ovarian cancer, PARP inhibition, cancer-related inflammation

  20. Sex-determining region Y-box3 (SOX3) functions as an oncogene in promoting epithelial ovarian cancer by targeting Src kinase.

    Science.gov (United States)

    Yan, Qin; Wang, Fangyuan; Miao, Yi; Wu, Xiaomei; Bai, Mingzhu; Xi, Xiaowei; Feng, Youji

    2016-09-01

    Ovarian cancer is one of the most common cancers which cause female mortality. The knowledge of ovarian cancer initiation and progression is critical to develop new therapeutic strategies to treat and prevent it. Recently, SOX3 has been reported to play a pivotal role in tumor progression. However, the clinical significance of SOX3 in human ovarian cancer remains elusive, and the identity of SOX3 in ovarian cancer initiation, progression, and the related underlying mechanism is unknown. In this study, we showed that SOX3 expression increased from benign and borderline to malignant ovarian tumors. Subsequently, we found that overexpression of SOX3 in EOC cells promoted proliferation, migration, and invasion, while restrained apoptosis and adhesion of ovarian cancer cells. In contrast, silencing of SOX3 gained the opposite results. Finally, we discovered SOX3 targeted Src kinase in EOC cells. These data imply that SOX3, acting as an oncogene in EOC, is not only a crucial factor in the carcinogenesis but also a promising therapeutic target for EOC.

  1. 基质金属蛋白酶2及CD147在卵巢上皮性肿瘤中的表达%Expression of matrix metalloproteinase-2 and CD147 in ovarian epithelial tumor

    Institute of Scientific and Technical Information of China (English)

    贺书云; 辛晓燕; 王健

    2001-01-01

    目的 了解基质金属蛋白酶(MMP-2)及CD147在卵巢良、恶性上皮性肿瘤中的表达,探讨其与卵巢癌转移发生的关系. 方法 用免疫组化SP法 对47例卵巢癌组织、19例交界性上皮性卵巢肿瘤、17例良性上皮性卵巢肿瘤组织中MMP-2及CD147的表达情况进行了检测. 结果 MMP-2在恶性及交界性上皮 性卵巢肿瘤中的强阳性表达率分别为59%,42%,明显高于良性组强阳性表达率30% (P<0.0 5),在卵巢癌中MMP-2的表达与卵巢癌的临床分期有关,Ⅲ~Ⅳ期卵巢癌强阳性表达率71%,明显高于Ⅰ~Ⅱ期卵巢癌强阳性表达率37% (P<0.05),与分化程度无明显关联,但有淋巴结转移的病例强阳性表达率87%,明显高于无淋巴结转移组. CD147在恶性及交界卵巢上皮性肿瘤中的强阳性表达率分别为64%,57%,而良性组则未见CD147的表达. 在卵巢癌中,CD147的强阳性表达率与临床分期有关,Ⅲ~Ⅳ期的癌组织强阳性表达率74%,明显高于Ⅰ~Ⅱ期强阳性表达率45%,在不同分化程度卵巢癌组织中CD147的强阳性率无明显差异,有无淋巴结转移的卵巢癌组织中CD147强阳性表达率差异显著. 结论 MMP-2 及CD147均与卵巢癌的分期及淋巴结转移有关,CD147与MMP-2的产生关系密切.%AIM To investigate the expression of matrix metall oproteinase-2 (MMP-2) and CD147 in ovarian epithelial tumor. METHODS The expression o f MMP-2 and CD147 was detected in malignant, borderline and benign ovarian tissues by immunohistochemical SP method. Monoclonal antibodies against MMP-2 and CD147 were used. RESULTS Intense expression rates o f MMP-2 in the malignant, borderline, benign epithelial tumor tissues of ovary was 59%, 42%, 30% respectively, There were a significant difference between malignant, borderline and benign tumors (P<0.05). In ovarian cancer, th e expression of MMP-2 had a significant relevance to clinical phases and lymph

  2. Expressions of matrix metalloproteinase-9,IV collagen and CD34 in epithelial ovarian tumor and its significance%基质金属蛋白酶-9、Ⅳ型胶原、CD34在卵巢上皮性肿瘤中的表达及意义

    Institute of Scientific and Technical Information of China (English)

    黄凯清; 柯佩奇; 梁立治; 彭文明; 彭娟; 刘少颜

    2010-01-01

    目的 探讨基质金属蛋白酶(MMP)-9、Ⅳ型胶原、CD34在卵巢上皮性肿瘤中的表达及意义.方法 卵巢上皮性肿瘤患者82例,其中卵巢恶性上皮性肿瘤48例,卵巢交界性上皮性肿瘤23例,卵巢良性上皮性肿瘤11例.采用免疫组化染色方法,检测MMP-9、Ⅳ型胶原和CD34在肿瘤组织中的表达情况.结果 MMP-9的表达强度随肿瘤恶性程度增加而增强(F=39.306,P<0.01).CD34的表达亦随肿瘤恶性程度增加而增强[卵巢良性上皮性肿瘤为(17.18±5.64)%,卵巢交界性上皮性肿瘤为(29.76±7.18)%,高分化卵巢恶性上皮性肿瘤为(57.20±8.55)%,中分化卵巢恶性上皮性肿瘤为(71.20±8.48)%,低分化卵巢恶性上皮性肿瘤为(90.38 ±20.03)%](F=100.072,P<0.01).Ⅳ型胶原在卵巢恶性上皮性肿瘤中的表达强度低于在卵巢交界性上皮性肿瘤和卵巢良性上皮性肿瘤中的表达强度(F=11.554,P<0.01). MMP-9表达与CD34表达、Ⅳ型胶原缺失表达均呈正相关(r值分别为0.802和0.796,P<0.01).结论 MMP-9、CD34表达随着卵巢上皮性肿瘤恶性程度的增加而增强,Ⅳ型胶原的表达在卵巢恶性上皮性肿瘤中明显减少.MMP-9表达与CD34表达、Ⅳ型胶原缺失表达呈正相关.通过联合检测MMP-9、CD34、Ⅳ型胶原在卵巢上皮性肿瘤中的表达对判断其恶性程度具有重要的临床意义.%Objective To explore the expression and significance of matrix metalloproteinase (MMP)-9, IV collagen and CD34 in epithelial ovarian tumor. Methods Eighty-two patients with epithelial ovarian tumor, among them,there were 48 malignant epithelial ovarian carcinomas, 23 borderline epithelial ovarian tumors and 11 benign epithelial ovarian tumors. The expression of MMP-9, IV collagen and CD34 were detected by immunohistochemistry. Results The expression of MMP-9 was strongly linked to the degree of malignant ovarian carcinomas (F= 39.306,P< 0.01). The expression of CD34 was also strongly linked to the degree of

  3. Malignant ovarian tumors complicating pregnancy:a clinicopathological study of twenty-one cases

    Institute of Scientific and Technical Information of China (English)

    Zhao Xue-ying; Huang Hui-fang; Lian Li-juan

    2004-01-01

    Objective: To study the clinicopathological characters of malignant ovarian tumors during pregnancy. The rationale for appropriate management was discussed.Methods: Twenty-one cases of malignant ovarian tumors complicating pregnancy treated between 1985 and 2002 were reviewed retrospectively. In reference with the reports from the current literatures, the rationale of the treatment for the best outcome of both mother and child was discussed.Results:In the patients reviewed, 9 were found with malignant germ cell tumors of the ovary, 6 with low malignant potential tumors, 4 with invasive epithelial tumors, and 2 with sex cord-stromal tumors. Sixteen (76.2 %) of the patients diagnosed in stage I, and all had achieved complete response to the treatment. Three of the four patients in advanced stage died, of which two were invasive epithelial cancers and one stage Ⅳ endodermal sinus tumor. All patients had surgery, and fourteen of them got conservative surgery. All sixteen patients accepted for chemotherapy took adjuvant chemotherapies after abortions or deliveries. Fourteen healthy live births were recorded in this group and there were no documented birth defects, but one died of respiratory distress syndrome.Conclusion: The managements of malignant ovarian cancers during pregnancy differed in different histological types. In ovarian borderline tumors and malignant germ cell tumors including stage Ⅰ, Ⅱ, and Ⅲ, surgery can be conservative. For advanced epithelial cancers, aggressive surgery should be instituted. Chemotherapy could be considered for the malignant germ cell tumor during the second and third trimester. Ovarian borderline tumors should not take chemotherapy.Epithelial cancer should be given combination platinum-based chemotherapy. Hysterectomy during pregnancy is rarely indicated unless it contributes significantly to tumor debulking, and pregnancy often could be allowed to continue until near-term.

  4. Expression of Snail and E-cadherin in Epithelial Ovarian Cancer and Their Relationship with Epithelial-Mesenchymal Transition%Snail和E-cadherin在上皮性卵巢癌组织中的表达及其与上皮-间叶转化的关系

    Institute of Scientific and Technical Information of China (English)

    郑艳萍; 姚爱香; 鄢学菊

    2011-01-01

    Objective: To investigate the expression of epithelial-mesenchymal transition (EMT) related markers Snail and E-cadherin proteins in epithelial ovarian carcinoma and their relationship with the malignant features.Methods: The expression of Snail and E-cadherin proteins was detected in 45 cases of epithelial ovarian cancer by immunohistochemistry method and its relationship with clinic pathological data was also analyzed.Results: Snail positive expression rate was 40 % (18/45) in 45 cases of ovarian cancer, while the decreased expression of E-cadherin was found in 23 cases.The expression of Snail was significantly related to lymph node metastasis (P<0.05), distant metastasis (P< 0.01 ), and the lower expression of E-cadherin (P< 0.05).There was a clear correlation of Snail increased expression and E-cadherin decreased expression with the metastasis of ovarian cancer.Conclusion: There exists the re-expression of Snail in ovarian cancer,accompanied by decreased E-cadherin expression.Controlling epithelial-mesenchymal transition might play an important role in the invasion process of ovarian cancer.%目的:探讨上皮-间叶细胞转变(EMT)的标记分子Snail和E-cadherin在上皮性卵巢癌组织中的表达及其与卵巢癌恶性生物学行为的相关性.方法:采用免疫组化方法分别检测45例卵巢上皮性癌组织中Snail和Ecadherin的表达状况,并分析其与卵巢癌主要临床病理参数之间的关系.结果:45例卵巢癌组织中Snail阳性表达率为40%(18/45),23例中观察到E-cadherin表达的降低.Snail的表达和淋巴结转移(P<0.05)、远处转移(P<0.01),E-cadherin表达降低(P<0.05)都存在着相关性.Snail的阳性表达和E-cadherin的表达降低与卵巢癌的转移存在着明显的相关性.结论:Snail在卵巢癌组织中存在着重新表达的现象,同时伴随着E-cadherin的表达降低,调控上皮-间叶转化从而在卵巢癌的侵袭过程中发挥重要作用.

  5. Targeted treatment of folate receptor-positive platinum-resistant ovarian cancer and companion diagnostics, with specific focus on vintafolide and etarfolatide.

    Science.gov (United States)

    Serpe, Loredana; Gallicchio, Margherita; Canaparo, Roberto; Dosio, Franco

    2014-01-01

    Among the gynecological malignancies, ovarian cancer is the leading cause of mortality in developed countries. Treatment of ovarian cancer is based on surgery integrated with chemotherapy. Platinum-based drugs (cisplatin and carboplatin) comprise the core of first-line chemotherapy for patients with advanced ovarian cancer. Platinum-resistant ovarian cancer can be treated with cytotoxic chemotherapeutics such as paclitaxel, topotecan, PEGylated liposomal doxorubicin, or gemcitabine, but many patients eventually relapse on treatment. Targeted therapies based on agents specifically directed to overexpressed receptors, or to selected molecular targets, may be the future of clinical treatment. In this regard, overexpression of folate receptor-α on the surface of almost all epithelial ovarian cancers makes this receptor an excellent "tumor-associated antigen". With appropriate use of spacers/linkers, folate-targeted drugs can be distributed within the body, where they preferentially bind to ovarian cancer cells and are released inside their target cells. Here they can exert their desired cytotoxic function. Based on this strategy, 12 years after it was first described, a folate-targeted vinblastine derivative has now reached Phase III clinical trials in ovarian cancer. This review examines the importance of folate targeting, the state of the art of a vinblastine folate-targeted agent (vintafolide) for treating platinum-resistant ovarian cancer, and its diagnostic companion (etarfolatide) as a prognostic agent. Etarfolatide is a valuable noninvasive diagnostic imaging agent with which to select ovarian cancer patient populations that may benefit from this specific targeted therapy.

  6. Late metastases of ovarian carcinoma. A case report.

    Science.gov (United States)

    Friedman, M; Browde, S; Rabin, S; Murray, J; Nissenbaum, M

    1984-02-01

    In cases of ovarian carcinoma distant metastases are rarely discovered before local spread has become evident. This article reports an unusual case in which renal metastases appeared 9 years after the initial diagnosis of epithelial ovarian carcinoma. A discussion of the histological features of the tumour and the spread of ovarian carcinoma is included.

  7. Differentiating pelvic actinomycosis from advanced ovarian cancer: a report of two cases, management reflections and literature review.

    Science.gov (United States)

    Laios, Alex; Terekh, Iryna; Majd, Hooman Soleymani; Pathiraja, Pubudu; Manek, Sanjiv; Haldar, Krishnayan

    2014-01-01

    Pelvic actinomycosis comprises a rare, subacute to chronic bacterial infection characterised by suppurative and granulomatous inflammation. Diagnosis is difficult as it may simulate pelvic malignancies. Laboratory and radiological findings are non-specific. We reported on 2 cases of pelvic actinomycosis mimicking ovarian malignancy with different management approaches that lead to opposite outcomes. We reviewed the literature on pelvic actinomycosis imitating ovarian cancer with a focus on its surgical management. Despite agreement on the duration of antibiotic therapy following surgical management, consensus regarding surgical approach was rather equivocal. We concluded that pelvic actinomycosis should be strongly suspected in women with presumed ovarian cancer of atypical presentation and a history of intrauterine devices (IUD).

  8. Cigarette smoking and risk of ovarian cancer

    DEFF Research Database (Denmark)

    Faber, Mette T; Kjær, Susanne K; Dehlendorff, Christian;

    2013-01-01

    The majority of previous studies have observed an increased risk of mucinous ovarian tumors associated with cigarette smoking, but the association with other histological types is unclear. In a large pooled analysis, we examined the risk of epithelial ovarian cancer associated with multiple...... measures of cigarette smoking with a focus on characterizing risks according to tumor behavior and histology....

  9. CA125 in ovarian cancer

    DEFF Research Database (Denmark)

    Duffy, M J; Bonfrer, J M; Kulpa, J

    2005-01-01

    value in the detection of early ovarian cancer. At present, therefore, CA125, either alone or in combination with other modalities, cannot be recommended for screening for ovarian cancer in asymptomatic women outside the context of a randomized controlled trial. Preoperative levels in postmenopausal...... women, however, may aid the differentiation of benign and malignant pelvic masses. Serial levels during chemotherapy for ovarian cancer are useful for assessing response to treatment. Although serial monitoring following initial chemotherapy can lead to the early detection of recurrent disease......CA125 is currently the most widely used tumor marker for ovarian epithelial cancer. The aim of this article is to provide guidelines for the routine clinical use of CA125 in patients with ovarian cancer. Due to lack of sensitivity for stage I disease and lack of specificity, CA125 is of little...

  10. 上皮性卵巢癌组织中WWOX基因启动子区域CpG岛的甲基化状态及临床意义%Methylation State of WWOX Gene Promoter CpG Islands in Epithelial Ovarian Cancer and Its Clinical Significance

    Institute of Scientific and Technical Information of China (English)

    闫洪超; 孙洁芸; 陆晓媛; 韩秋峪; 魏敏

    2012-01-01

    目的 研究上皮性卵巢癌组织中WWOX基因启动子区CpG岛的甲基化状态,并分析WWOX基因的甲基化与上皮性卵巢癌的临床病理指标之间的关系.方法 采用甲基化特异性PCR(methylation specific polymerase chain reaction,MSP)方法检测48例上皮性卵巢癌、18例卵巢交界性上皮性肿瘤、26例卵巢良性上皮性肿瘤及33例正常卵巢组织中WWOX基因CpG岛甲基化状态.结果 上皮性卵巢癌、卵巢交界性上皮性肿瘤、卵巢良性上皮性肿瘤组织中WWOX基因启动子区CpG岛甲基化率分别为43.75%、26.32%、3.84%,正常卵巢组织中未检测到WWOX基因CpG岛甲基化.上皮性卵巢癌组织中WWOX基因CpG岛的甲基化率明显高于其他卵巢组织,差异有统计学意义(P<0.01).晚期(Ⅲ期、Ⅳ期)上皮性卵巢癌组织中WWOX基因CpG岛的甲基化率高于早期(Ⅰ期、Ⅱ期)上皮性卵巢癌组织,差异有统计学意义(P<0.05).结论 上皮性卵巢癌组织中广泛存在着WWOX基因启动子区CpG岛甲基化,可能是导致WWOX基因失活的重要机制.WWOX基因的异常甲基化可能与上皮性卵巢癌的发生发展密切相关,其可能成为上皮性卵巢癌的早期诊断和评估预后的重要指标.%Objective To evaluate the methylation status of CpG islands in WWOX gene promoter region of epithelial ovarian cancer, and to explore the relationship between methylation state of WWOX gene CpG island and clinicopathological indexes in epithelial ovarian cancer. Methods The methylation state of WWOX gene CpG island was evaluated by methylation specific polymerase chain reaction(MSP) in 48 patients with epithelial ovarian cancer, 18 patients with borderline epithelial ovarian tumors,26 patients with epithelial benign tumors,and 33 patients with normal ovarian tissues. Results The rates of CpG island methylation in WWOX gene promoter region in epithelial ovarian cancer tissues,borderline ovarian tumor tissues and benign ovarian tumor

  11. The role of microRNAs in the tumorigenesis of ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Gianpiero eDi Leva

    2013-06-01

    Full Text Available Epithelial ovarian cancer (EOC is a complex disease, with multiple histological subtypes recognized. There have been major advances in the understanding of the cellular and molecular biology of this human malignancy, however the survival rate of women with epithelial ovarian cancer has changed little since platinum based-treatment was introduced more than 30 years ago. Since 2006, an increasing number of studies have indicated an essential role for microRNAs in ovarian cancer tumorigenesis. Several microRNA profiling studies have shown that they associate with different aspects of ovarian cancer (tumor subtype, stage, histological grade, prognosis and therapy resistance and pointed to a critical role for microRNAs in the pathogenesis and progression of EOC. In this review, we discuss the current data concerning the accumulating evidence of the modulated expression of microRNAs in EOC, their role in diagnosis, prognosis and prediction of response to therapy. Given the heterogeneity of this disease, it is likely that increases in long-term survival might be also achieved by translating the recent insights of miRNAs involvement in EOC into novel targeted therapies that will have a major impact on the management of ovarian cancer.

  12. Serum folate receptor alpha as a biomarker for ovarian cancer: Implications for diagnosis, prognosis and predicting its local tumor expression.

    Science.gov (United States)

    Kurosaki, Akira; Hasegawa, Kosei; Kato, Tomomi; Abe, Kenji; Hanaoka, Tatsuya; Miyara, Akiko; O'Shannessy, Daniel J; Somers, Elizabeth B; Yasuda, Masanori; Sekino, Tetsuo; Fujiwara, Keiichi

    2016-04-15

    Folate receptor alpha (FRA) is a GPI-anchored glycoprotein and encoded by the FOLR1 gene. High expression of FRA is observed in specific malignant tumors of epithelial origin, including ovarian cancer, but exhibits very limited normal tissue expression, making it as an attractive target for the ovarian cancer therapy. FRA is known to shed from the cell surface into the circulation which allows for its measurement in the serum of patients. Recently, methods to detect the soluble form of FRA have been developed and serum FRA (sFRA) is considered a highly promising biomarker for ovarian cancer. We prospectively investigated the levels of sFRA in patients clinically suspected of having malignant ovarian tumors. A total of 231 patients were enrolled in this study and analyzed for sFRA as well as tumor expression of FRA by immunohistochemistry. High sFRA was predominantly observed in epithelial ovarian cancer patients, but not in patients with benign or borderline gynecological disease or metastatic ovarian tumors from advanced colorectal cancers. Levels of sFRA were highly correlated to clinical stage, tumor grade and histological type and demonstrated superior accuracy for the detection of ovarian cancer than did serum CA125. High sFRA was significantly associated with shorter progression-free survival in both early and advanced ovarian cancer patients. Finally, tumor FRA expression status was strongly correlated with sFRA levels. Taken together, these data suggest that sFRA might be a useful noninvasive serum biomarkers for future clinical trials assessing FRA-targeted therapy.

  13. Differentiating pelvic actinomycosis from advanced ovarian cancer: a report of two cases, management reflections and literature review

    OpenAIRE

    2014-01-01

    Pelvic actinomycosis comprises a rare, subacute to chronic bacterial infection characterised by suppurative and granulomatous inflammation. Diagnosis is difficult as it may simulate pelvic malignancies. Laboratory and radiological findings are non-specific. We reported on 2 cases of pelvic actinomycosis mimicking ovarian malignancy with different management approaches that lead to opposite outcomes. We reviewed the literature on pelvic actinomycosis imitating ovarian cancer with a focus on it...

  14. Antiangiogenic therapies in ovarian cancer

    OpenAIRE

    Reinthaller, Alexander

    2016-01-01

    Summary Angiogenesis plays a pivotal role in normal ovarian physiology as well as in the formation and progression of ovarian cancer. Several well-designed phase II and III trials studied the efficacy of antiangiogenic agents in advanced ovarian cancer. The results of these trials demonstrated significantly prolonged progression-free survival when antiangiogenic agents were used as a maintenance therapy. To date, no effect on overall survival could be ascertained. The most widely studied anti...

  15. Epigenetic analysis leads to identification of HNF1B as a subtype-specific susceptibility gene for ovarian cancer

    DEFF Research Database (Denmark)

    Shen, Hui; Fridley, Brooke L; Song, Honglin

    2013-01-01

    HNF1B is overexpressed in clear cell epithelial ovarian cancer, and we observed epigenetic silencing in serous epithelial ovarian cancer, leading us to hypothesize that variation in this gene differentially associates with epithelial ovarian cancer risk according to histological subtype. Here we ...

  16. Procyanidin-rich extract of natural cocoa powder causes ROS-mediated caspase-3 dependent apoptosis and reduction of pro-MMP-2 in epithelial ovarian carcinoma cell lines.

    Science.gov (United States)

    Taparia, Shruti Sanjay; Khanna, Aparna

    2016-10-01

    Over the last four centuries, cocoa and chocolate have been described as having potential medicinal value. As of today, Theobroma cacao L. (Sterculiaceae) and its products are consumed worldwide. They are of great research interest because of the concentration dependent antioxidant as well as pro-oxidant properties of some of their polyphenolic constituents, specially procyanidins and flavan-3-ols such as catechin. This study was aimed at investigating the cellular and molecular changes associated with cytotoxicity, caused due pro-oxidant activity of cocoa catechins and procyanidins, in ovarian cancer cell lines. Extract of non-alkalized cocoa powder enriched with catechins and procyanidins was used to treat human epithelial ovarian cancer cell lines OAW42 and OVCAR3 at various concentrations ≤1000μg/mL. The effect of treatment on intracellular reactive oxygen species (ROS) levels was determined. Apoptotic cell death, post treatment, was evaluated microscopically and using flow cytometry by means of annexin-propidium iodide (PI) dual staining. Levels of active caspase-3 as a pro-apoptotic marker and matrix metalloproteinase 2 (MMP2) as an invasive potential marker were detected using Western blotting and gelatin zymography. Treatment with extract caused an increase in intracellular ROS levels in OAW42 and OVCAR3 cell lines. Bright field and fluorescence microscopy of treated cells revealed apoptotic morphology and DNA damage. Increase in annexin positive cell population and dose dependent upregulation of caspase-3 confirmed apoptotic cell death. pro-MMP2 was found to be downregulated in a dose dependent manner in cells treated with the extract. Treated cells also showed a reduction in MMP2 activity. Our data suggests that cocoa catechins and procyanidins are cytotoxic to epithelial ovarian cancer, inducing apoptotic morphological changes, DNA damage and caspase-3 mediated cell death. Downregulation of pro-MMP2 and reduction in active MMP2 levels imply a decrease

  17. Cost of illness of advanced ovarian carcinoma in Italy: results of an empirical, single-centre study

    Directory of Open Access Journals (Sweden)

    Carlo Lazzaro

    2015-09-01

    Full Text Available AIM: To perform an empirical, single-centre, retrospective and secondary cost of illness (COI study of advanced ovarian carcinoma (AOC in Italy. METHODS: Demographic, clinical, health care and non-health care resource consumption data concerning a convenience sample of subsequent patients in 1st line of treatment (100 patients, 2nd line of treatment A (surgery + chemotherapy; 30 patients and 2nd line of treatment B (chemotherapy only; 20 patients were obtained from a database created in 2011 by the Obstetrics and Ginecology Unit at Campus Biomedico teaching hospital, Rome. Patients were followed-up for 2 years. Resources were valued according to the above mentioned database and literature, following the societal viewpoint. Costs are expressed in Euro (€ 2014 and reported as mean and standard deviation (SD. RESULTS: One-year COI for 1st line of treatment reaches € 44,999.7 (SD: €28,757.3, € 55,410.8 (SD: € 32,454.6 and €46,895.6 (SD: € 28,407.4 for 2nd line of treatment A and B, respectively. Regardless the line of treatment, COI is mainly driven by cost borne by patient and her family. Due to the high costs of relapse the mean COI per patient after 2 years from the diagnosis of AOC equals € 81,869.4 (SD: € 30,660.9, or 182% of the COI for the 1st line of treatment. CONCLUSIONS: Despite some limitations, our results show that increasing progression-free survival could well reduce the COI for AOC in Italy.

  18. Translational research in ovarian carcinoma : cell biological aspects of drug resistance and tumor aggressiveness

    NARCIS (Netherlands)

    Zee, Ate Gerard Jan van der

    1994-01-01

    In this thesis diverse cell biological features that in cultured (ovarian) tumor cells have been linked to drug resistance and/or tumor aggressiveness are studied in tumor specimens of epithelial ovarian carcinomas.

  19. Evaluation of candidate stromal epithelial cross-talk genes identifies association between risk of serous ovarian cancer and TERT, a cancer susceptibility "hot-spot"

    DEFF Research Database (Denmark)

    Johnatty, Sharon E; Beesley, Jonathan; Chen, Xiaoqing;

    2010-01-01

    SNPs-PODXL rs1013368, ITGA6 rs13027811, and MMP3 rs522616-were selected for replication using TaqMan genotyping in up to 3,059 serous invasive cases and 8,905 controls from 16 OCAC case-control studies. An additional 18 SNPs with Pper-alleleor=0.5). However genotypes at TERT rs7726159 were associated...... with ovarian cancer risk in the smaller, five-study replication study (Pper-allele=0.03). Combined analysis of the discovery and replication sets for this TERT SNP showed an increased risk of serous ovarian cancer among non-Hispanic whites [adj. ORper-allele 1.14 (1.04-1.24) p=0.003]. Our study adds...

  20. Identification of miRNA Signatures Associated with Epithelial Ovarian Cancer Chemoresistance with Further Biological and Functional Validation of Identified Key miRNAs

    Science.gov (United States)

    2015-02-01

    maintenance of normal stem cells during embryonic development [e.g., Notch , Wnt, and Hedgehog] are also important for the growth of many cancers ...uncovered the biological relevance of this miRNA. We found that miR-181a induced platinum-resistance through the maintenance of cancer stem cells ...primary tumors. Most recently, the first stem - cell population that was able to give rise to ovarian cancers was identified in mice. Cells located

  1. High-Dose Estrogen and Clinical Selective Estrogen Receptor Modulators Induce Growth Arrest, p21, and p53 in Primate Ovarian Surface Epithelial Cells

    Energy Technology Data Exchange (ETDEWEB)

    Wright, Jay W.; Stouffer, Richard L.; Rodland, Karin D.

    2005-06-09

    Ovarian cancer is the most lethal gynecological cancer affecting women. Hormone-based therapies are variably successful in treating ovarian cancer, but the reasoning behind these therapies is paradoxical. Clinical reagents such as tamoxifen are considered to inhibit or reverse tumor growth by competitive inhibition of the estrogen receptor (ER); however high dose estrogen is as clinically effective as tamoxifen, and it is unlikely that estrogen is acting by blocking ER activity; however, it may be activating a unique function of the ER that is nonmitogenic. For poorly defined reasons, 90% of varian cancers derive from the ovarian surface epithelium (OSE). In vivo the ER-positive OSE is exposed to high estrogen levels, reaching micromolar concentrations in dominant ovarian follicles. Using cultured OSE cells in vitro, we show that these levels of estradiol (1 ug/ml; {approx}3um) block the actions of serum growth factors, activate the G1 phase retinoblastoma AQ:A checkpoint, and induce p21, an inhibitor of kinases that normally inactivate the retinoblastoma checkpoint. We also show that estradiol increases p53 levels, which may contribute to p21 induction. Supporting the hypothesis that clinical selective ER modulators activate this novel ER function, we find that micromolar doses of tamoxifen and the ''pure antiestrogen'' ICI 182,780 elicit the same effects as estradiol. We propose that, in the context of proliferation, these data clarify some paradoxical aspects of hormone-based therapy and suggest that fuller understanding of normal ER function is necessary to improve therapeutic strategies that target the ER. (J Clin Endocrinol Metab 90: 0000-0000, 2005)

  2. The Influence of Cyst Emptying, Lymph Node Resection and Chemotherapy on Survival in Stage IA and IC1 Epithelial Ovarian Cancer

    DEFF Research Database (Denmark)

    Rosendahl, Mikkel; Mosgaard, Berit Jul; Høgdall, Claus

    2016-01-01

    AIM: To determine if survival in stage I ovarian cancer is influenced by cyst emptying, lymph node resection and chemotherapy. PATIENTS AND METHODS: A survival analysis of 607 patients with ovarian cancer in stage IA, IA with cyst emptying (IAempty) and IC1 was performed. RESULTS......: There was no difference in five-year survival between IA (87%) and IC1 (87%) (p=0.899), between IA and IAempty (86%) (p=0.500) nor between IA+IAempty (87%) and IC1 without IAempty (84%) (p=0.527). Five-year survival rate (5YSR) was significantly higher after lymph node resection in stage IA (94% vs. 85%; p=0.01) and IA......+IC1 (93% vs. 85%; p=0.004). In multivariate analysis, lymph node resection improved prognosis significantly for all sub-stages, whereas stage and chemotherapy did not affect survival. CONCLUSION: In stage IA ovarian cancer, controlled cyst emptying without spill does not worsen prognosis. Lymph node...

  3. Highly and moderately aggressive mouse ovarian cancer cell lines exhibit differential gene expression

    Science.gov (United States)

    Zhang, Wensheng; Kale, Shubha P.; McFerrin, Harris; Davenport, Ian; Wang, Guangdi; Skripnikova, Elena; Li, Xiao-Lin; Bowen, Nathan J.; McDaniels, Leticia B; Meng, Yuan-Xiang; Polk, Paula; Liu, Yong-Yu; Zhang, Qian-Jin

    2017-01-01

    Patients with advanced epithelial ovarian cancer often experience disease recurrence after standard therapies, a critical factor in determining their five-year survival rate. Recent reports indicated that long-term or short-term survival is associated with varied gene expression of cancer cells. Thus, identification of novel prognostic biomarkers should be considered. Since the mouse genome is similar to the human genome, we explored potential prognostic biomarkers using two groups of mouse ovarian cancer cell lines (group 1: IG-10, IG-10pw, and IG-10pw/agar; group 2: IG-10 clones 2, 3, and 11) which display highly and moderately aggressive phenotypes in vivo. Mice injected with these cell lines have different survival time and rates, capacities of tumor, and ascites formations, reflecting different prognostic potentials. Using an Affymetrix Mouse Genome 430 2.0 Array, a total of 181 genes were differentially expressed (Pdeath. None of the genes from a set of the 72 genes overexpressed in the moderately aggressive cell lines had a function annotation in the David database. Our results suggested that the overexpressed MYC and 109 gene set represented highly aggressive ovarian cancer potential biomarkers while overexpressed AR and 72 gene set represented moderately aggressive ovarian cancer potential biomarkers. Based on our knowledge, the current study is first time to report the potential biomarkers relevant to different aggressive ovarian cancer. These potential biomarkers provide important information for investigating human ovarian cancer prognosis. PMID:26935058

  4. Gene Expression Profiles as Prognostic Marker in Women with Ovarian Cancer

    DEFF Research Database (Denmark)

    Jochumsen, Kirsten Marie; Tan, Qihua; Høgdall, EV;

    2009-01-01

    toward investigations for more individualized therapies and the use of gene expression profiles in the clinical practice. RNA from tumor tissue from 43 Danish patients with serous epithelial ovarian carcinoma (11 International Federation of Gynecology and Obstetrics [FIGO] stage I/II, 32 FIGO stage III......-term survivors (median overall survival of 32 months) from long-term survivors (median overall survival not yet reached after a median follow-up of 76 months) with a P value of 3.4 x 10 was found. The prognostic gene set was also able to distinguish short-term from long-term survival in patients with advanced......The purpose was to find a gene expression profile that could distinguish short-term from long-term survivors in our collection of serous epithelial ovarian carcinomas. Furthermore, it should be able to stratify in an external validation set. Such a classifier profile will take us a step forward...

  5. 40岁以下妇女卵巢上皮癌62例临床分析%Clinical analysis of 62 women with epithelial ovarian cancer under age of 40 years

    Institute of Scientific and Technical Information of China (English)

    唐莉; 叶旭彬; 吴雪薇

    2014-01-01

    Objective To investigate the clinical characteristics, treatment, survival rate and prognosis factors of the young women with epithelial ovarian cancer. Methods Clinical data of 62 women with epithelial ovarian cancer under the age of 40 years treated in our hospital from January 1990 to December 2012 were analyzed retrospectively. The survival rate was calculated using the life table.The cox model was used to analyze and compare the factors influencing prognosis. Results Sixty-two patients diagnosed with epithelial ovarian cancer had a median age of (31.3±1.6) years. Physical examination found abdominal mass in 17 patients and stomachache and abdominal distension in 12 patients respectively.The average maximum radial line of lump was (13.15±2.17) cm.Fifty-seven patients could receive satisfaction cytoreductive surgery.Thirty-seven patients were in surgical pathological stage I,accounting for 59.67%,7 patients stage Ⅱ,accounting for 11.29%,13 patients stage Ⅲ,accounting for 20.96%,and 5 patients stage IV,accounting for 8.06%. Pathological differentiation degrees were mainly serous adenocarcinoma (35 patients,56.45%) and mucinous adenocarcinoma(18 patients,29.03%).In terms of pathological differentiation degree,38 patients(61.2%) were highly differentiated,15 patient (24.2%) were moderately differentiated and 9 patients (14.5%) were poorly differentiated.Fifty-nine patients received preoperative and postoperative chemotherapy based on platinum or taxanes.Of the 12 patients receiving conservative surgery(all patients were Ia and G1),10 patients survived without tumor(83.34%).The 3-year survival rate calculated based on the life table method was 86.7%and the 5-year survival rate was 78.3%. Conclusion For the women with epithelial ovarian cancer under the age of 40 years,the size of tumor is large,unilateral is mostly seen, surgical pathological staging is early, pathological differentiation degree is good,serous cystadenocarcinoma is mostly seen,the total 5-year

  6. Ovarian reserve

    NARCIS (Netherlands)

    Macklon, NS; Fauser, BCJM

    2005-01-01

    The tendency to delay childbirth has increased the importance of ovarian reserve as a determinant of infertility treatment outcome. In the context of assisted reproduction technology, effective strategies to overcome the impact of ovarian aging and diminished ovarian reserve on pregnancy chances rem

  7. Combined Detection of Serum Matrix Metalloproteinase 9, Acetyl Heparinase and Cathepsin L in Diagnosis of Ovarian Cancer

    Institute of Scientific and Technical Information of China (English)

    Wei Zhang; Xiao-xia Hu; Xing-zhi Yang; Qi Wang; Hong Cheng; Shu-mei Wang; Yan-ling Hu; Zhi-jun Yang; Li Li

    2012-01-01

    Objective:To investigate the clinic values of combining test of serum matrix metalloproteinase 9 (MMP-9),acetyl heparinase (Hpa) and Cathepsin L (CL) in diagnosis of ovarian cancer.Methods:Serum levels of MMP-9,Hpa and CL were detected in a total of 418 cases,including 217 cases with ovarian malignant tumor,100 cases with ovarian benign tumor and 101 healthy controls,by using enzyme-linked immunosorbent assay (ELISA).Their correlation with clinicopathologic feature of ovarian malignant tumor was analyzed and their diagnosis performance was evaluated by receiver operating characteristic (ROC).The combined diagnosis model was established by logistic regression analysis.Results:The serum levels of MMP-9,Hpa and CL were significantly higher in patients with ovarian malignant tumor than in benign tumor and healthy control,the serum levels of CL and Hpa were higher in epithelial cancer than in non-epithelial tumor,and MMP-9,Hpa and CL were elevated in low grade and advanced stage compared to high grade and early stage.The sensitivity for diagnosis of ovarian malignant tumor from high to low was CL,Hpa and MMP-9,and the specificity was MMP-9,CL and Hpa.The united diagnosis model was established and showed the sensitivity and specificity of combined detection were 84.6% and 82.1%,respectively,which were significantly higher than a single tumor marker.Conclusion:Serum MMP-9,Hpa and CL were correlated with ovarian malignant tumor and the combined detection of which may be valuable for clinical diagnosis of ovarian malignant tumor.

  8. Pegylated liposomal doxorubicin in the management of ovarian cancer

    Directory of Open Access Journals (Sweden)

    Gabriella Ferrandina

    2010-09-01

    Full Text Available Gabriella Ferrandina1,2, Giacomo Corrado1, Angelo Licameli1, Domenica Lorusso2, Gilda Fuoco1, Salvatore Pisconti3, Giovanni Scambia2 1Gynecologic Oncology Unit, Department of Oncology, Catholic University of Campobasso, Campobasso, Italy; 2Gynecologic Oncology Unit, Catholic University of Rome, Rome, Italy; 3Salvatore Pisconti, Oncology Unit, Taranto Hospital, Taranto, Italy Abstract: Among the pharmaceutical options available for treatment of ovarian cancer, much attention has been progressively focused on pegylated liposomal doxorubicin (PLD, whose unique formulation, which entraps conventional doxorubicin in a bilayer lipidic sphere ­surrounded by a polyethylene glycol layer, prolongs the persistence of the drug in the ­circulation and potentiates intratumor drug accumulation. These properties enable this drug to sustain its very favorable toxicity profile and to be used safely in combination with other drugs. PLD has been already approved for treatment of advanced ovarian cancer patients failing first-line platinum-based treatment. Moreover, phase III trials have been already completed, and results are eagerly awaited, which hopefully will expand the range of PLD clinical application in this neoplasia both in front-line treatment, and in the salvage setting in combination with other drugs. Moreover, attempts are continuing to enable this drug to be combined with novel cytotoxic drugs and target-based agents. This review aims at summarizing the available evidence and the new perspectives for the clinical role of PLD in the management of patients with epithelial ovarian cancer.Keywords: pegylated liposomal doxorubicin, ovarian cancer, clinical trials

  9. Prognostic value of plasma soluble urokinase plasminogen activator receptor (suPAR) in Danish patients with recurrent epithelial ovarian cancer (REOC)

    DEFF Research Database (Denmark)

    Begum, Farah Diba; Høgdall, Estrid V S; Riisbo, Rikke

    2006-01-01

    The level of the soluble urokinase plasminogen activator receptor (suPAR) is elevated in tumour tissue from several types of cancer. This is the first study aiming to predict the prognosis for survival by the use of a pre-chemotherapeutic plasma suPAR value in 71 patients with recurrent epithelial...

  10. The research development of potent suppression mechanisms of NK cells response mediated by MUC16 in epithelial ovarian cancer%MUC16介导卵巢癌细胞免疫逃逸NK细胞杀伤的研究进展

    Institute of Scientific and Technical Information of China (English)

    金夏; 赵卫东

    2011-01-01

    过继性自体NK细胞免疫治疗临床应用的效果不明显可能与肿瘤在恶化过程中对NK细胞的免疫逃逸有关,MUC16作为一种表达于卵巢癌上皮细胞表面的跨膜黏蛋白可能参与了卵巢癌细胞对NK细胞杀伤作用的免疫逃逸.因而了解MUC16介导卵巢癌细胞免疫逃逸NK细胞杀伤作用的相关性研究很重要.%The fact that there is no significant clinical benefit of autologous NK cell immunotherapy may be associated with the immune escape of ovarian cells in tumor progression . MUC16 is a membrane spanning mucin that is expressed on ovarian surface epithelial cells. This mucin may participate in the immune escape of ovarian cancer cells to NK cell killing effect. In this review, we summarized the relative researches a-bout potent suppression mechanisms of NK cells response mediated by MUC16 in epithelial ovarian cancer.

  11. Identification of miRNA Signatures Associated with Epithelial Ovarian Cancer Chemoresistance with Further Biological and Functional Validation of Identified Key miRNAS

    Science.gov (United States)

    2016-04-01

    were upregulated in the platinum resistant variants compared to the parental sensitive cell line. Well-known miRNA clusters such as the miR-17-92 and...associated with chemotherapy response were analyzed in the panel of platinum-resistant ovarian cancer cell lines. Taqman PCR analysis confirmed that 4 (miR...Figure 2). In addition, rather then comparing two distinct groups (i.e., sensitive vs. resistant), we directly correlated the level of each miRNA

  12. Ovarian cancer plasticity and epigenomics in the acquisition of a stem-like phenotype

    Directory of Open Access Journals (Sweden)

    Berry Nicholas B

    2008-11-01

    Full Text Available Abstract Aggressive epithelial ovarian cancer (EOC is genetically and epigenetically distinct from normal ovarian surface epithelial cells (OSE and early neoplasia. Co-expression of epithelial and mesenchymal markers in EOC suggests an involvement of epithelial-mesenchymal transition (EMT in cancer initiation and progression. This phenomenon is often associated with acquisition of a stem cell-like phenotype and chemoresistance that correlate with the specific gene expression patterns accompanying transformation, revealing a plasticity of the ovarian cancer cell genome during disease progression. Differential gene expressions between normal and transformed cells reflect the varying mechanisms of regulation including genetic changes like rearrangements within the genome, as well as epigenetic changes such as global genomic hypomethylation with localized promoter CpG island hypermethylation. The similarity of gene expression between ovarian cancer cells and the stem-like ovarian cancer initiating cells (OCIC are surprisingly also correlated with epigenetic mechanisms of gene regulation in normal stem cells. Both normal and cancer stem cells maintain genetic flexibility by co-placement of activating and/or repressive epigenetic modifications on histone H3. The co-occupancy of such opposing histone marks is believed to maintain gene flexibility and such bivalent histones have been described as being poised for transcriptional activation or epigenetic silencing. The involvement of both-microRNA (miRNA mediated epigenetic regulation, as well as epigenetic-induced changes in miRNA expression further highlight an additional complexity in cancer stem cell epigenomics. Recent advances in array-based whole-genome/epigenome analyses will continue to further unravel the genomes and epigenomes of cancer and cancer stem cells. In order to illuminate phenotypic signatures that delineate ovarian cancer from their associated cancer stem cells, a priority must lie

  13. Mechanism of drug resistance and reversal with ligustra-zine and cyclosporin A in cisplatin-induced human epithelial ovarian cancer resistant cell line 3Ao/cDDP

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To investigate the mechanism of resistance and reversal effect of ligustrazine and cyclosporin A in cisplatin-induced multidrug resistance ovarian cancer cell line 3Ao/cDDP. Methods: Using the corresponding dose calculated from clinical chemotherapy at 30 mg cisplatin per cycle, we established 3Ao/cDDP with 3Ao exposed at regular intervals and repeatedly to high-level concentration of cisplatin at 10 m g/ml for 24 hours each time. Expressions of LRP, MRP, P-gp, GSTp and TopoII were quantitatively detected with FCM. For drug resistance reversal, cyclosporin A and ligustrazine were administered singly or in combination at the maximal dose without cytotoxicity. Inhibition rates were determined by MTT assay. Results: 3Ao/cDDP was established after 4.5 months, with resistance factor 1.6 which was similar to clinical resistance degree. Low expression levels of MRP and P-gp were found in both 3Ao and 3Ao/cDDP (P>0.05), and LRP and GSTp expression levels in 3Ao/cDDP were significantly higher than those in 3Ao (P0.05 vs cDDP), cDDP plus cyclosporin A 49.635± 0.021% (P<0.01 vs cDDP), and cDDP plus ligustrazine and cyclosporin A 58.861± 0.014% (P<0.01 vs cDDP). Conclusions: 3Ao/cDDP, induced by cisplatin and established by imitating the characteristics of clinical chemotherapy for epithelial ovarian cancer, was an ideal model for investigation of cisplatin resistance in vitro. Cisplatin resistance in 3Ao/cDDP could be accounted for by higher LRP, GSTp and lower TopoII expression and was not associated with MRP or P-gp. Ligustrazine had no significant reversal effect on cisplatin resistance, but cyclosporin A could reverse the resistance effectively.

  14. CXXC指蛋白5在上皮性卵巢癌中的表达及其临床意义%Effects of CXXC ifnger protein 5 up-regulated expression in epithelial ovarian cancer

    Institute of Scientific and Technical Information of China (English)

    汪景灏; 任渊; 张蓉; 韩英; 盛友华; 侯文静; 敖洪峰

    2015-01-01

    背景与目的:上皮性卵巢癌是最常见的卵巢肿瘤类型,发病率高,治疗效果不满意,生存率低。CXXC指蛋白5(CXXC finger protein 5,CXXC5)在上皮性卵巢癌中的研究鲜见报道,该研究通过对CXXC5在上皮性卵巢癌中的表达和对上皮性卵巢癌细胞功能的研究,旨在探讨CXXC5在上皮性卵巢癌中可能的作用和临床意义。方法:①通过肿瘤基因图集(The Cancer Genoma Atlas,TCGA)数据库提供的数据分析CXXC5在上皮性卵巢癌基因组中的变异;②通过免疫组织化学法(immunohistochemistry,IHC)检测CXXC5在上皮性卵巢癌组织芯片中的表达情况,并分析CXXC5的表达与临床病理特征之间的关系;③通过蛋白[质]印迹法(Western blot)和实时定量PCR(real-time quantitative PCR,qRT-PCR)检测CXXC5在5株上皮性卵巢癌细胞系中的表达情况,选取表达量最高的ES-2细胞株;④使用慢病毒包装质粒转染ES-2细胞株,经嘌呤霉素筛选后构建稳定转染干扰细胞株;使用细胞计数试剂盒(cell counting kit-8,CCK8)检测细胞增殖能力的变化。结果:①CXXC5在TCGA提供的上皮性卵巢癌基因组中以表达为主;②CXXC5在上皮性卵巢和卵巢良性上皮性囊肿中的高表达率分别为39.3%和13.5%,差异有统计学意义(P=0.003);CXXC5在浆液性卵巢癌、黏液性卵巢癌、子宫内膜样卵巢癌和卵巢透明细胞癌中的高表达率分别为43.0%、22.9%、23.5%和66.7%,两两比较差异均有统计学意义(P均=0.014);CXXC5在有淋巴结转移和无淋巴结转移的上皮性卵巢癌中表达率为60.0%和35.8%,差异有统计学意义(P=0.022);③CXXC5稳定干扰后,卵巢癌透明细胞株ES-2的增殖能力明显减弱,差异有统计学意义(P<0.05)。结论:CXXC5基因可能有促进卵巢癌细胞增殖的作用,可能是上皮性卵巢癌预后不良的生物标志物。%Background and purpose:Epithelial ovarian cancer

  15. BUB1 mRNA is significantly co-expressed with AURKA and AURKB mRNA in advanced-stage ovarian serous carcinoma.

    Science.gov (United States)

    Davidson, Ben; Nymoen, Dag Andre; Elgaaen, Bente Vilming; Staff, Anne Cathrine; Tropé, Claes G; Kærn, Janne; Reich, Reuven; Falkenthal, Thea E Hetland

    2014-06-01

    The objective of this study was to investigate the expression and clinical role of the spindle checkpoint kinase budding uninhibited by benzimidazole 1 (Bub1) in primary and metastatic advanced-stage ovarian serous carcinoma. BUB1 mRNA expression was analyzed in 178 tumors (88 effusions, 38 primary carcinomas, and 52 solid metastases) from 144 patients with advanced-stage disease using quantitative real-time polymerase chain reaction (PCR). Bub1 protein expression by Western blotting was studied in 63 carcinomas (30 effusions and 33 solid lesions). BUB1 mRNA expression at different anatomic sites was studied for association with clinicopathologic parameters, including chemotherapy resistance and survival. BUB1 mRNA was universally expressed in serous carcinomas, irrespective of anatomic site. BUB1 mRNA levels were uniformly low in six ovarian surface epithelium specimens analyzed for comparative purposes. Bub1 protein was expressed in 22/30 effusions and 28/33 solid lesions. BUB1 mRNA expression was significantly higher in chemo-naïve primary carcinomas and solid metastases compared to specimens obtained following neoadjuvant chemotherapy (p cancer. BUB1 mRNA levels are lower following chemotherapy exposure in solid lesions, though its presence is unrelated to clinical behavior including response to chemotherapy and survival. BUB1 is co-expressed with AURKA and AURKB suggesting biological relationship between these spindle cell components.

  16. Fibroblast growth factor receptor 4 gene (FGFR4) 388Arg allele predicts prolonged survival and platinum sensitivity in advanced ovarian cancer.

    Science.gov (United States)

    Marmé, Frederik; Hielscher, Thomas; Hug, Sarah; Bondong, Sandra; Zeillinger, Robert; Castillo-Tong, Dan Cacsire; Sehouli, Jalid; Braicu, Ioana; Vergote, Ignace; Isabella, Cadron; Mahner, Sven; Ferschke, Irmgard; Rom, Joachim; Sohn, Christof; Schneeweiss, Andreas; Altevogt, Peter

    2012-08-15

    FGFR4 has been shown to play an important role in the etiology and progression of solid tumors. A single nucleotide polymorphism (SNP) within the FGFR4 gene has previously been linked to prognosis and response to chemotherapy in breast cancer and other malignancies. This study evaluates the relevance of this SNP in advanced ovarian cancer. FGFR4-genotype was analyzed in 236 patients recruited as part of the OVCAD project. Genotyping was performed on germ-line DNA using a TaqMan based genotyping assay. Results were correlated with clinicopathological variables and survival. The FGFR4 388Arg genotype was significantly associated with prolonged progression-free and overall survival (univariate: HR 0.68, p = 0.017; HR 0.49, p = 0.005; multivariate: HR 0.69, p = 0.025; HR 0.49, p = 0.006) though the positive prognostic value was restricted to patients without postoperative residual tumor. Indeed, there was a significant interaction between FGFR4 genotype and residual tumor for overall survival. Furthermore, the FGFR4 388Arg genotype significantly correlated with platinum sensitivity in the same subgroup (multivariate OR 3.81 p = 0.004). FGFR4 Arg388Gly genotype is an independent and strong context specific prognostic factor in patients with advanced ovarian cancer and could be used to predict platinum-sensitivity.

  17. The relationship of the angiogenesis regulators VEGF-A, VEGF-R1 and VEGF-R2 to p53 status and prognostic factors in epithelial ovarian carcinoma in FIGO-stages I-II.

    Science.gov (United States)

    Skirnisdottir, Ingiridur; Seidal, Tomas; Åkerud, Helena

    2016-03-01

    The aim of this study was to evaluate prognostic effect of the angiogenesis regulators VEGF-R1, VEGF-R2 and VEGF-A for recurrent disease and disease-free survival (DFS), and their relation to the apoptosis regulator p53, in 131 patients with FIGO-stages I-II with epithelial ovarian cancer. For the detection of positivity of the markers the techniques of tissue microarrays and immunohistochemistry (IHC) were used. In tumors the frequency of positive staining for VEGF-R1 was 19%, for VEGF-R2 and VEGF-A, it was 77 and 70%, respectively. Positivity for p53 was detected in 25% of tumors. The total number of recurrences in the complete series was 34 out of 131 (26%) and 5-year disease-free survival (DFS) was 68%. Positive staining for VEGF-A (P=0.030), VEGF-R2 (P=0.011) and p53 (P=0.015) was found more frequently in type II tumors than in type I tumors. Patients with VEGF-R1 negative tumors had worse (P=0.021) DFS compared to patients with VEGF-R1 positive tumors. In two multivariate Cox analyzes with DFS as endpoint, FIGO-stage (HR=3.8), VEGF-R2 status (HR=0.4) and p53 status (HR=2.3), all were significant and independent prognostic factors. When the variables VEGF-R2 and p53 were replaced with the new variable VEGF-R2+p53-/other three combinations in one group, it was found that patients from that subgroup had 86% reduced risk of dying in disease (HR=0.24). Findings above, confirmed relationship between VEGF-R2 and VEGF-A and p53, respectively, with regard to recurrent disease and survival. Some findings from the present study are different from results from previous studies on the regulation of angiogenesis. Despite many trials with anti-angiogenic agents in the front line of ovarian cancer have shown to be positive for progression-free survival, no one has demonstrated an impact on overall survival. Therefore, one of the greatest challenges in ovarian cancer research, is to discover predictive and prognostic biomarkers.

  18. Relação entre tumores ovarianos epiteliais borderline e francamente invasores: epidemiologia, histologia e prognóstico The relationship between borderline and invasive epithelial ovarian tumors: epidemiology, histology and prognosis

    Directory of Open Access Journals (Sweden)

    Sophie F. Mauricette Derchain

    1999-06-01

    Full Text Available Objetivo: avaliar alguns aspectos epidemiológicos, do diagnóstico e do prognóstico em mulheres com tumores epiteliais ovarianos borderline e francamente invasores. Métodos: foram revisados os prontuários de 198 pacientes tratadas no CAISM/UNICAMP de 1986 a 1996. Para análise estatística foram utilizados os testes chi², exato de Fisher, t de Student e curvas de sobrevida pelo método de Kaplan-Meyer comparadas pelo teste log-rank. O seguimento médio das pacientes foi de 50 meses (de 11 a 168. Dos 198 casos, 24 eram tumores borderline (12% e 174 (88% carcinomas francamente invasores. Resultados: a média de idade das pacientes com tumores borderline foi significativamente menor que a das mulheres com carcinoma francamente invasor: 43 ± 14,8 anos vs 52 ± 12,6 anos (pPurpose: to determine some epidemiological, diagnostic and prognostic aspects in women with borderline and invasive epithelial ovarian tumors. Methods: the charts of 198 women treated at CAISM/UNICAMP from 1986 to 1996 were revised. For statistical assessment, chi², Fisher's exact and t Student's tests were used when appropriate, followed by survival curves by the Kaplan-Meyer method, compared by the log-rank test. The mean follow-up was 50 months (11 to 168. Results: the overall rate of borderline tumors was 12% (24 cases, and for invasive carcinoma, 88% (174 cases. The mean age of the patients with borderline tumors was significantly lower than that of those with invasive carcinoma (43 ± 14.8 years vs. 52 ± 12.6 years, p<0.002. The most frequent histologic types were the serous (81 cases: 41% and the mucinous (46 cases: 23% tumor. The women with borderline tumors had their diseases diagnosed in earlier stages when compared with the invasive carcinoma patients (p<0.0001. The frozen biopsy, performed on 77 patients, showed a high agreement with the paraffin fixed tissue in the invasive carcinoma cases. However, in borderline tumors, the rate of failure was higher (13% and

  19. 上皮性卵巢癌患者 LDL 与 ox-LDL 的诊价值及与预后的关系%Diagnostic values of LDL and ox-LDL in patients with epithelial ovarian cancer and their relationship with prognosis

    Institute of Scientific and Technical Information of China (English)

    周晅; 周彦杰; 李新春

    2015-01-01

    目的:研究血清中低密度脂蛋白(LDL)和氧化型低密度脂蛋白(ox‐LDL )在临床诊断的价值,同时分析其与上皮性卵巢癌患者预后的相关性。方法选取2010年4月至2014年5月入院治疗的40例良性上皮性卵巢肿瘤患者、28例上皮性卵巢癌患者,以及同期来体检的30例健康体检者,比较各组标本血清中高密度脂蛋白、三酰甘油、LDL 和总胆固醇水平,分析血脂水平变化与上皮性卵巢癌分化的关系,同时对 LDL 及 ox‐LDL 水平与患者远期生存预测相关性进行分析。结果上皮性卵巢癌患者血清中 ox‐LDL 、LDL 水平显著高于健康体检者,差异有统计学意义(P<0.05);高分化型上皮性卵巢癌患者 ox‐LDL 和 LDL 水平显著高于其低、中分化型患者,差异有统计学意义(P<0.05);LDL 及 ox‐LDL 水平与患者远期生存预测有相关性。结论 LDL 及 ox‐LDL 水平改变是上皮性卵巢癌患者远期临床预后的重要预测因素,具有重要临床意义。%Objective To study the diagnostic values of serum low density lipoprotein (LDL) and oxidation of serum lipoprotein (ox‐LDL ) in patients with epithelial ovarian cancer and their relationship with prognosis . Methods 40 cases of patients with ovarian tumor ,28 cases of patients with epithelial ovarian cancer ,and 30 cases of healthy people were enrolled in the study from April 2010 to May 2014 .The serum levels of high density lipoprotein in serum (HDL) ,three glycerol (TG) ,LDL and ox‐LDL of each group were detected and compared .The relationship between the changes of lipid levels and the differentiation of epithelial ovarian cancer was analyzed ,and the correlation between the levels of LDL and ox‐LDL and the long‐term survival prediction was also analyzed .Results The serum levels of ox‐LDL and LDL in patients with epithelial ovarian cancer were significantly higher than healthy people (P< 0 .05

  20. Expressions of chemokine SDF-1 and its receptor CXCR4 in epithelial ovarian tumor of elderly patients and its clinical significance%SDF-1/CXCR4在老年卵巢癌组织中的表达及意义

    Institute of Scientific and Technical Information of China (English)

    李雅丽; 辛维政; 王轶英

    2011-01-01

    Objective To investigate the expressions and clinical significance of chemokine SDF-1 and its receptor CXCR4 in elderly patients with epithelial ovarian tumor. Methods 43 cases with epithelial ovarian cancer were studied ran-domly. The expressions of SDF-1 and CXCR4 proteins were detected by Western blotting. Results There were weak ex-pression of SDF-1 and modest expression of CXCR4 in benign ovarian tumor of elderly patients. The expressions of SDF-1 protein and CXCR4 protein were significantly increased in epithelial ovarian cancer, compared with benign ovarian tumor (2.38±0.20 vs 3.32±0.26) (P<0.05). Conclusion SDF-1/CXCR4 may play a role in the malignant transformation of primary ovarian cancer and involve in the initiation, progression and metastasis of ovarian cancer of elderly patients.%目的 探讨趋化因子SDF-1及其受体CXCR4在老年人卜皮性卵巢癌组织中的表达及意义.方法 应用western blotting方法定量检测43例老年患者卜皮性卵巢癌组织中SDF-1和CXCR4的蛋白表达情况.结果 老年人上皮性卵巢癌组织中SDF-1/CXCR4蛋白表达较卵巢良性肿瘤对照组明显增加.其相对表达量分别为(2.38±0.20)和(3.32±0.26),差异具有统计学意义(P<0.05).结论 SDF-1/CXCR4生物学轴可能在老年人卵巢癌的发生与转移过程中起着重要作用.

  1. Expression and clinical significance of Snail and NF- κB in epithelial ovarian carcinoma%锌指结构转录抑制因子Snail及NF-κB在卵巢上皮癌中的表达及临床意义

    Institute of Scientific and Technical Information of China (English)

    周金金; 张玲玲

    2012-01-01

    Objective The purpose of this study was to detect Snail and NF - κB in epithelial ovarian carcinoma, analyze the relationship between the expression of them both and clinical pathological feature of epithelial ovarian cancer. Methods 59 ovarian neoplasm wax blocks was collected from pathology department of Yang Zhou NO. 1 hospital from 2005 to 2010 and BaoYing people's hospital from 2007 to 2010, meanwhile, 18 benign tumor specimens were collected as control group. The expression of Snail and NF- κB were detect by immunohistochemical. Within the results, we employed spss 16.0 to analyze the relationship between the expression of Snail, NF- κB and clinicopathologic parameters. Results the positive expression of Snail and NF - κB were higher in ovarian cancer than in benign, they were positive correlation in expression. Conclusion There was up - regulated expression of Snail and NF - κB protein in epithelial ovarian carcinoma. The higher stage of ovarian carcinoma the stronger them expressed. NF - κB expression was correlated with Snail, it may play cooperation role with Snail in the ovarian cancer metastasis.%目的 通过对卵巢上皮癌组织中Snail、NF-κB的检测,探讨其在卵巢上皮癌中的表达及临床意义.方法 卵巢恶性肿瘤59例,良性上皮性肿瘤18例,应用免疫组化方法检测其在良恶性卵巢肿瘤的表达情况.结果 Snail及NF-κB在卵巢上皮癌的表达明显高于良性上皮,两者呈正相关.结论 Snail,NF- κB在卵巢上皮癌中高表达,卵巢癌期别越高,表达越强,NF-κB与Snail在卵巢癌的发展过程中可能起协同作用.

  2. Granisetron, Aprepitant, and Dexamethasone in Preventing Nausea and Vomiting in Patients Receiving Chemotherapy for Stage II, III, or IV Ovarian Cancer

    Science.gov (United States)

    2016-03-16

    Malignant Ovarian Mixed Epithelial Tumor; Nausea and Vomiting; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Stage II Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer; Undifferentiated Ovarian Carcinoma

  3. Research Advances of Nanotechnology in Ovarian Carcinoma%纳米技术在卵巢癌中的研究进展

    Institute of Scientific and Technical Information of China (English)

    刘思思(综述); 周英琼(审校)

    2016-01-01

    Ovarian cancer is one of the most common malignant tumors in the female reproductive sys-tem,with concealed early onset,late stage diagnosis and high mortality.Because of the small diameter,uni-form distribution, better tissue compatibility and target localization ability after surface modification , nano material has become one of the hot topics in the research of diagnosis and treatment of ovarian cancer .Here is to make a review of the most recent advances of the characteristics of different nano carriers and nanotechnol-ogy in ovarian cancer cell specific capture,ultrasound,computed tomography and magnetic resonance imaging diagnosis,chemotherapy,radiotherapy and gene therapy.%卵巢癌是女性生殖系统最常见的恶性肿瘤之一,早期起病隐匿,确诊多为中期晚,致死率高。纳米材料因其直径小、分布均匀,经表面修饰后的纳米粒子具有较好的组织相容性以及靶向定位能力,日益成为卵巢癌诊断和治疗的研究热点之一。该文综述了纳米药物不同载体的特性、纳米技术在卵巢癌肿瘤细胞特异捕获及超声、计算机断层扫描、磁共振成像等在化疗、放疗和基因治疗中的最新研究进展。

  4. 卵巢上皮癌患者疾病不确定感对生活质量的影响%Influence of sense of Disease Uncertainty on Life Quality in Patients with Epithelial Ovarian Cancer

    Institute of Scientific and Technical Information of China (English)

    孙春燕; 郑莉彦; 李炳芬; 杨宏; 王坤

    2011-01-01

    目的 探讨卵巢上皮癌患者疾病不确定感对生活质量的影响.方法 选择我院住院的卵巢上皮癌59例为观察组,同期住院的非卵巢癌45例为对照组,分别在入院后1周内及出院前1 d接受Missals疾病不确定感量表和世界卫生组织生存质量测定量表(WHO-QOL-BREF)评估,并以疾病不确定感评分62.5分为界,第2次评估数据为依据,将观察组分为高分组和低分组,行生活质量评价.结果 2次疾病不确定感评估≥62.5分观察组分别为29例(49.15%)和17例(28.81%),对照组分别为8例(17.78%)和5例(11.11 %),差异均有统计学意义(P<0.01);观察组2次不确定感各维度评分及总分均高于对照组,差异有统计学意义(P<0.05,P<0.01);两组第2次疾病不确定感各维度评分及总分均低于第1次,差异有统计学意义(P<0.05,P<0.01).卵巢上皮癌高分组4个领域评分和总生活评分、总健康评分均显著低于低分组,差异有统计学意义(P<0.05,P<0.01).结论 加强初治卵巢癌患者的健康教育,及早帮助其掌握疾病相关常识及治疗情况,使其积极配合治疗,可降低疾病不确定感,提高生活质量.%Objective To investigate the assessment of sense of disease uncertainty in patients with epithelial ovarian cancer, and to discuss the influences of disease uncertainty on life quality. Methods 59 hospitalized patients with epithelial ovarian cancer were chosen as observation group, and 45 non- epithelial ovarian cancer patients were chosen as control group at the same time. The patients in the two groups received the assessment of Missals MUIS and WHO-QOL-BREF respectively within 1 week after hospitalization and 1 d before being discharged from hospital. Using the second assessment data as a judgment and 62. 5 of the disease uncertainty score as a dividng line, the observation group was divided into high-score group and low-score group to assess life quality. Results 29 patients (49. 15% ) and

  5. Cancer Vaccines in Ovarian Cancer: How Can We Improve?

    Directory of Open Access Journals (Sweden)

    Silvia Martin Lluesma

    2016-05-01

    Full Text Available Epithelial ovarian cancer (EOC is one important cause of gynecologic cancer-related death. Currently, the mainstay of ovarian cancer treatment consists of cytoreductive surgery and platinum-based chemotherapy (introduced 30 years ago but, as the disease is usually diagnosed at an advanced stage, its prognosis remains very poor. Clearly, there is a critical need for new treatment options, and immunotherapy is one attractive alternative. Prophylactic vaccines for prevention of infectious diseases have led to major achievements, yet therapeutic cancer vaccines have shown consistently low efficacy in the past. However, as they are associated with minimal side effects or invasive procedures, efforts directed to improve their efficacy are being deployed, with Dendritic Cell (DC vaccination strategies standing as one of the more promising options. On the other hand, recent advances in our understanding of immunological mechanisms have led to the development of successful strategies for the treatment of different cancers, such as immune checkpoint blockade strategies. Combining these strategies with DC vaccination approaches and introducing novel combinatorial designs must also be considered and evaluated. In this review, we will analyze past vaccination methods used in ovarian cancer, and we will provide different suggestions aiming to improve their efficacy in future trials.

  6. 腹腔灌注与静脉化疗治疗晚期卵巢癌的疗效对比研究%The Comparative Study of the Effect of Intraperitoneal Perfusion and Intravenous Chemotherapy in Advanced Ovarian ;Cancer

    Institute of Scientific and Technical Information of China (English)

    闫玉兰; 张冬梅; 王英; 姜明哲

    2014-01-01

    目的:比较单纯静脉给药化疗与腹腔灌注化疗2种给药途径治疗晚期上皮性卵巢癌的临床疗效。方法:选取天津市第五中心医院62例晚期上皮性卵巢癌患者,将患者随机分为静脉滴注组和腹腔灌注组。静脉滴注组方案:紫杉醇135 mg/m2静脉滴注,24 h后顺铂75 mg/m2静脉滴注;腹腔灌注组方案:紫杉醇135 mg/m2静脉滴注,24 h后顺铂100 mg/m2腹腔灌注,第8天给予紫杉醇60 mg/m2腹腔灌注。所有患者进行随访,分别对2组患者的近期疗效、远期疗效和不良反应等进行比较。结果:腹腔灌注组肿瘤缓解率较静脉滴注组有增高趋势,但差异无统计学意义(P>0.05);腹腔灌注组的疾病无进展生存期(progression-free survival,PFS)和2年生存率均显著高于静脉滴注组,差异有统计学意义(P<0.01)。腹腔灌注组的不良反应发生率高于静脉滴注组,2组贫血、肝功能损害及神经毒性发生率差异有统计学意义(P<0.05)。结论:腹腔灌注化疗可有效提高晚期上皮性卵巢癌患者的PFS和2年生存率,改善患者预后。%Objective:Compare with the efficacy of intravenous chemotherapy and intraperitoneal chemotherapy in two different administration methods of advanced epithelial ovarian cancer. Methods:Select 62 patients who were diagnosed advanced epithelial ovarian cancer in the Tianjin NO.5 Central Hospital, the patients were randomly divided into intravenous chemotherapy and intraperitoneal perfusion group. Intravenous drip group scheme:paclitaxel 135 mg/m2 intravenous infusion in the first day,cisplatin after 24 h 75 mg/m2 intravenously. Intraperitoneal perfusion group scheme:paclitaxel intravenous infusion of 135 mg/m2 in the first day,24 h after cisplatin 100 mg/m2 intraperitoneal,and paclitaxel 60 mg/m2 intraperitoneal perfusion in the eighth day. All patients were followed,compared short-term and long-term efficacy and adverse

  7. Alterations of c-Myc and c-erbB-2 genes in ovarian tumours

    Directory of Open Access Journals (Sweden)

    Pastor Tibor

    2009-01-01

    Full Text Available Introduction. According to clinical and epidemiological studies, ovarian cancer ranks fifth in cancer deaths among women. The causes of ovarian cancer remain largely unknown but various factors may increase the risk of developing it, such as age, family history of cancer, childbearing status etc. This cancer results from a succession of genetic alterations involving oncogenes and tumour suppressor genes, which have a critical role in normal cell growth regulation. Mutations and/or overexpression of three oncogenes, c-erbB-2, c-Myc and K-ras, and of the tumour suppressor gene p53, have been frequently observed in a sporadic ovarian cancer. Objective. The aim of the present study was to analyze c-Myc and c-erbB-2 oncogene alterations, specifically amplification, as one of main mechanisms of their activation in ovarian cancers and to establish a possible association with the pathogenic process. Methods. DNA was isolated from 15 samples of malignant and 5 benign ovarian tumours, using proteinase K digestion, followed by phenol-chloroform isoamyl extraction and ethanol precipitation. C-Myc and c-erbB-2 amplification were detected by differential PCR. The level of gene copy increase was measured using the Scion image software. Results. The amplification of both c-Myc and c-erbB-2 was detected in 26.7% of ovarian epithelial carcinoma specimens. Only one tumour specimen concomitantly showed increased gene copy number for both studied genes. Interestingly, besides amplification, gene deletion was also detected (26.7% for c-erbB-2. Most of the ovarian carcinomas with alterations in c-Myc and c-erbB-2 belonged to advanced FIGO stages. Conclusion. The amplification of c-Myc and c-erbB-2 oncogenes in ovarian epithelial carcinomas is most probably a late event in the pathogenesis conferring these tumours a more aggressive biological behaviour. Similarly, gene deletions point to genomic instability in epithelial carcinomas in higher clinical stages as the

  8. Functional redundancy of the Notch pathway in ovarian cancer cell lines.

    Science.gov (United States)

    Silva, Fernanda; Félix, Ana; Serpa, Jacinta

    2016-10-01

    Epithelial ovarian cancer is the most lethal gynecologic malignancy, despite advances in treatment. The most common histological type, high-grade ovarian serous carcinoma (OSC) is usually diagnosed at an advanced stage, and although these types of tumors frequently respond to surgery and platinum-based chemotherapy, they usually recur. Ovarian clear cell carcinoma (OCCC) is an unusual histological type, which is known to be intrinsically chemoresistant and is associated with poor prognosis in advanced stages. In recent years, genetic alterations and epigenetic modulation of signaling pathways have been reported in OSC and OCCC, including the overexpression of Notch pathway elements and histone deacetylases. Histone deacetylase inhibitors (HDACis), including vorinostat (suberoylanilide hydroxamic acid), alter the transcription of genes involved in cell growth, survival and apoptosis, and have become an attractive therapeutic approach. However, no previous work has addressed the effect of HDACis, and in particular vorinostat, on Notch signaling in ovarian cancer. Therefore, the present study aimed to investigate the modulation of the Notch pathway by vorinostat in ovarian cancer. Using immunofluorescence and quantitative polymerase chain reaction, the present results revealed that vorinostat activated the Notch pathway in OCCC and OSC cell lines, through different Notch ligands. In OCCC, the activation of the Notch pathway appeared to occur through Delta-like (Dll) ligands 1, 2 and 3, whereas in OSC Dll1 and Jagged 1 and 2 ligands were involved. The activation of the Notch pathway by vorinostat, in OCCC and OSC cell lines, culminated in the increased expression of the same downstream transcription factors, hairy enhancer of split (Hes) 1 and 5, and Hes-related proteins 1 and 2. In conclusion, vorinostat modulates the expression of several downstream targets of the Notch pathway and independent Notch receptors and ligands that are expressed in OSC and OCCC. This

  9. Expression of the novel gene NM23-H1B in ovarian cancer

    Institute of Scientific and Technical Information of China (English)

    LI Wen; LIU Yan; JIN Zhi-Jun; FENG You-ji; XU Ling-ling

    2005-01-01

    Objective:To study the expression of the human novel gene NM23-H1B in ovarian cancer. Methods: Totally 24 samples from patients with epithelial ovarian tumor at different clinical stages and 4 from normal ovaries were examined for NM23-H1B mRNA expression by RT-PCR and Northern blot. Results: All samples expressed NM23-H1B mRNA through RT-PCR, while the level of expression in ovarian tumor was higher than that of normal ovary. The results of Northern blot showed that NM23-H1B was overexpressed in ovarian cancer while lowexpressed in normal ovary or low malignant potential (LMP). The level of expression at early stage cancer(stageⅠand Ⅱ) was higher than those in advanced cancer(stage Ⅲ and Ⅳ). In early stage carcinoma, the expression level was involved in the differentiation of tumor cell, and well-differentiated cancer expressed NM23-H1B mRNA in comparatively higher level. Conclusion: The novel gene NM23-N1B is closely correlated with the ovarian cancer.

  10. Vascular intervention treatment role and signiifcance in patients with advanced ovarian cancer and cervical cancer%血管介入治疗对晚期卵巢癌与宫颈癌的治疗作用及意义

    Institute of Scientific and Technical Information of China (English)

    吕峰泉; 李焕祥; 刘武军; 马彦寿

    2015-01-01

    ObjectiveTo analysis of vascular interventional therapy in the treatment of patients with advanced ovarian cancer and cervical cancer role and signiifcance.Methods30 cases of advanced ovarian cancer and 30 cases of cervical cancer patients with vascular interventional therapy, and 30 cases of advanced ovarian cancer and 30 cases of cervical cancer patients with traditional surgery.ResultsThe vascular interventional treatment of patients with advanced ovarian cancer and cervical cancer patients with efficient and survival rate were obviously higher than that of traditional surgical treatment of patients, with signiifcant difference (P<0.05). ConclusionVascular interventional treatment of advanced ovarian cancer, and cervical cancer patients had a higher therapeutic effect and signiifcance.%目的分析血管介入治疗对晚期卵巢癌与宫颈癌的治疗作用及意义。方法30例晚期卵巢癌及30例宫颈癌患者采用血管介入治疗,另外30例晚期卵巢癌及30例宫颈癌患者采用传统手术治疗。结果晚期卵巢癌与宫颈癌患者血管介入治疗的有效率、存活率都明显高于传统手术治疗的患者,差异具有统计学意义(P<0.05)。结论血管介入治疗晚期卵巢癌与宫颈癌患者有较高的治疗作用及意义。

  11. Reach of NLR and CA-1 25 in the early diagnosis of epithelial ovarian cancer%中性粒细胞与淋巴细胞比值联合癌抗原-125对上皮性卵巢癌早期诊断的研究

    Institute of Scientific and Technical Information of China (English)

    石纳玉; 邓月月; 吴迪; 石瑞生

    2015-01-01

    Objectives:In order to discuss the significance of the application which combing the NLR with CA -1 25 together about early diagnosis epithelial ovarian cancer.Methods:60 cases with initial ovarian carcinoma from our gynecology and obstetrics were selected as a study group.Selecting the 60 cases of ovarian carcinoma begin and 60 normal women as control groups.to evaluate the NLR to diagnose the critical value of epithelial ovarian cancer by using ROC curves,and the joint application of critical value and CA -1 25 in order to judge that whether it have advantages of improving the susceptibility and specificity of ovarian carcinoma or not.Results:by using ROC curves to evaluate the NLR to diagnose ,the critical value were 2.8.The susceptibility,specificity were 0.72,0.83.By combing NLR with CA -1 25 to diagnose the epithelial ovarian cancer’s susceptibility,specificity, positive predictive value,negative predictive value,correct index.There were 0.87,0.85,0.85,0.86,and 0.72.Conclusions:The application of NLR have higher susceptibility,and specificity about epithelial ovarian cancer.Combing NLR with CA -1 25 can improve the susceptibility and specificity of early diagnosis of epithelial o-varian cancer.%目的:探讨应用外周血中性粒细胞与淋巴细胞比值(NLR)联合癌抗原-125(CA -125)对上皮性卵巢癌早期诊断的意义。方法:选取来我院妇科初治的卵巢癌患者60例为研究组,选取同期我院60例卵巢良性肿瘤患者与60例健康女性为良性对照组与健康对照组,通过受试者回归曲线(ROC 曲线)测定NLR 诊断上皮性卵巢癌的临界值,并与 CA -125联合诊断判断 NLR 联合 CA -125对提高鉴别卵巢包块良恶性中的敏感性与特异性中是否有优势。结果:通过 ROC 曲线测定 NLR 诊断上皮性卵巢癌的临界值2.8,敏感度0.72、特异度0.83,NLR 联合 CA -125诊断上皮性卵巢癌的敏感度、特异度、阳性预测值、阴

  12. WWOX CNV-67048 Functions as a Risk Factor for Epithelial Ovarian Cancer in Chinese Women by Negatively Interacting with Oral Contraceptive Use

    Directory of Open Access Journals (Sweden)

    Yongxiu Chen

    2016-01-01

    Full Text Available Copy number variations (CNVs have attracted increasing evidences to represent their roles as cancer susceptibility regulators. However, little is known about the role of CNV in epithelia ovarian cancer (EOC. Recently, the CNV-67048 of WW domain-containing oxidoreductase (WWOX was reported to alter cancer risks. Considering that WWOX also plays a role in EOC, we hypothesized that the CNV-67048 was associated with EOC risk. In a case-control study of 549 EOC patients and 571 age (±5 years matched cancer-free controls, we found that the low copy number of CNV-67048 (1-copy and 0-copy conferred a significantly increased risk of EOC (OR = 1.346, 95% CI = 1.037–1.747 and it determined the risk by means of copy number-dependent dosage effect (P=0.009. Data from TCGA also confirmed the abovementioned association as the frequency of low copies in EOC group was 3.68 times more than that in healthy group (P=0.023. The CNV also negatively interacted with oral contraceptive use on EOC risk (P=0.042. Functional analyses further showed a lower mRNA level of WWOX in tissues with the 0-copy or 1-copy than that in those with the 2-copy (P=0.045. Our data suggested the CNV-67048 to be a risk factor of EOC in Chinese women.

  13. Targeted treatment of folate receptor-positive platinum-resistant ovarian cancer and companion diagnostics, with specific focus on vintafolide and etarfolatide

    Directory of Open Access Journals (Sweden)

    Serpe L

    2014-01-01

    Full Text Available Loredana Serpe, Margherita Gallicchio, Roberto Canaparo, Franco DosioDepartment of Drug Science and Technology, University of Turin, ItalyAbstract: Among the gynecological malignancies, ovarian cancer is the leading cause of mortality in developed countries. Treatment of ovarian cancer is based on surgery integrated with chemotherapy. Platinum-based drugs (cisplatin and carboplatin comprise the core of first-line chemotherapy for patients with advanced ovarian cancer. Platinum-resistant ovarian cancer can be treated with cytotoxic chemotherapeutics such as paclitaxel, topotecan, PEGylated liposomal doxorubicin, or gemcitabine, but many patients eventually relapse on treatment. Targeted therapies based on agents specifically directed to overexpressed receptors, or to selected molecular targets, may be the future of clinical treatment. In this regard, overexpression of folate receptor-α on the surface of almost all epithelial ovarian cancers makes this receptor an excellent "tumor-associated antigen". With appropriate use of spacers/linkers, folate-targeted drugs can be distributed within the body, where they preferentially bind to ovarian cancer cells and are released inside their target cells. Here they can exert their desired cytotoxic function. Based on this strategy, 12 years after it was first described, a folate-targeted vinblastine derivative has now reached Phase III clinical trials in ovarian cancer. This review examines the importance of folate targeting, the state of the art of a vinblastine folate-targeted agent (vintafolide for treating platinum-resistant ovarian cancer, and its diagnostic companion (etarfolatide as a prognostic agent. Etarfolatide is a valuable noninvasive diagnostic imaging agent with which to select ovarian cancer patient populations that may benefit from this specific targeted therapy.Keywords: vintafolide, etarfolatide, platinum-resistant ovarian cancer, targeted therapy, biomarkers, folate receptor

  14. Progress of Ovarian Cancer Stem Cells and Epithelial-mesenchymal Transition%卵巢癌干细胞与上皮-间质转化的研究进展

    Institute of Scientific and Technical Information of China (English)

    尧晓芬; 赖东梅

    2014-01-01

    近年有研究指出肿瘤可能是肿瘤干细胞性疾病。随着各种肿瘤干细胞不断被分离与鉴定出来,卵巢癌干细胞的分离与鉴定也取得了进展。卵巢癌干细胞是卵巢癌中具有自我更新和多向分化能力的细胞。越来越多的证据表明,肿瘤干细胞可能是介导肿瘤转移和耐药的关键细胞。同时,研究发现上皮-间质转化(EMT)在肿瘤转移中发挥着重要作用,且EMT可能介导肿瘤细胞获得干细胞特性。综述卵巢癌干细胞与EMT之间的关系,进一步探讨卵巢癌的潜在治疗策略。%Cancer as a disease driven by cancer stem cells is a concept that has emerged over the last few years. Along with varieties of cancer stem cells (CSCs) have been identified,the isolation and identification of ovarian cancer stem cells(OCSCs) developes quickly. OCSCs is a self-renewal and differentiation of cells. Re-cently,increasing evidences suggest that CSCs are potential candidates for mediating metastatic progression and chemoresistance. Studies have also indicated the process of epithelial-mesenchymal transition (EMT) plays an important role in regulating cancer metastasis. Meanwhile ,more and more findings illustrate a direct link between the EMT and the gain of stem-cell properties. The purpose of this review is to discuss the relationship between OCSCs and EMT,and to explore the potential therapeutic strategies of ovarian cancer.

  15. Defining Therapy for Recurrent Platinum-sensitive Ovarian Cancer

    Science.gov (United States)

    In this phase III clinical trial, women with platinum-sensitive, recurrent ovarian epithelial, fallopian tube, or primary peritoneal cancer will be randomly assigned to undergo secondary cytoreductive surgery, if they are candidates for such surgery, and

  16. PAX2 Expression in Low Malignant Potential Ovarian Tumors and Low-Grade Ovarian Serous Carcinomas

    Science.gov (United States)

    Tung, Celestine S.; Mok, Samuel C.; Tsang, Yvonne T.M.; Zu, Zhifei; Song, Huijuan; Liu, Jinsong; Deavers, Michael; Malpica, Anais; Wolf, Judith K.; Lu, Karen H.; Gershenson, David M.; Wong, Kwong-Kwok

    2009-01-01

    Ovarian tumors of low-malignant potential and low-grade ovarian serous carcinomas are thought to represent different stages on a tumorigenic continuum and to develop along pathways distinct from high-grade ovarian serous carcinoma. We performed gene expression profiling on 3 normal human ovarian surface epithelia samples, and 10 low-grade and 10 high-grade ovarian serous carcinomas. Analysis of gene expression profiles of these samples has identified 80 genes up-regulated and 232 genes down-regulated in low-grade ovarian serous carcinomas. PAX2 was found to be one of the most up-regulated genes in low-grade ovarian serous carcinoma. The up-regulation of PAX2 was validated by real-time quantitative RT-PCR, Western blot and immunohistochemical analyses. Real-time RT-PCR demonstrated a statistically significant difference in PAX2 mRNA expression (expressed as fold change in comparison to normal human ovarian surface epithelia) among ovarian tumors of low-malignant potential (1837.38, N=8), low-grade (183.12, N=17), and high-grade (3.72, N=23) carcinoma samples (p=0.015). Western blot analysis revealed strong PAX2 expression in ovarian tumors of low-malignant potential (67%, N=3) and low-grade carcinoma samples (50%, N=10) but no PAX2 protein expression in high-grade carcinomas (0%, N=10). Using immunohistochemistry, tumors of low-malignant potential (59%, N=17) and low-grade carcinoma (63%, N=16) samples expressed significantly stronger nuclear staining than high-grade ovarian carcinoma samples (9.1%, N=263). Furthermore, consistent with previous immunohistochemical findings, PAX2 expression was found to be expressed in the epithelial cells of fallopian tubes but not in normal ovarian surface epithelial cells. Our findings further support the two-tiered hypothesis that tumors of low-malignant potential and low-grade ovarian serous carcinoma are on a continuum and are distinct from high-grade ovarian carcinomas. Additionally, the absence of PAX2 expression in normal

  17. Targeting the Mevalonate Pathway to Reduce Mortality from Ovarian Cancer

    Science.gov (United States)

    2015-10-01

    AWARD NUMBER: W81XWH-14-1-0221 TITLE: Targeting the Mevalonate Pathway to Reduce Mortality from Ovarian Cancer PRINCIPAL INVESTIGATOR: Kala...AND SUBTITLE: Targeting the Meval onate Pathway to Reduce Mortality from Ovarian Cancer 5a. CONTRACT NUMBER W81XWH-14-1-0221 5b. GRANT NUMBER...cost. 15. SUBJECT TERMS: cancer mortality, cholesterol-lowering drugs, disease progression, epithelial ovarian cancer , lovastatin, Mevalonate Pathway

  18. A Phase I Study of Unimolecular Pentavalent (Globo-H-GM2-sTn-TF-Tn Immunization of Patients with Epithelial Ovarian, Fallopian Tube, or Peritoneal Cancer in First Remission

    Directory of Open Access Journals (Sweden)

    Roisin E. O’Cearbhaill

    2016-04-01

    Full Text Available We conducted a phase I study in ovarian cancer patients to evaluate the safety and immunogenicity of a synthetic unimolecular pentavalent carbohydrate vaccine (Globo-H, GM2, sTn, TF, and Tn supported on a peptide backbone, conjugated to keyhole limpet haemocyanin (KLH, and mixed with immunological adjuvant QS-21. Twenty-four advanced-stage, poor-risk, first-remission ovarian cancer patients were enrolled from January 2011–Septermber 2013. Three dose levels were planned (25, 50, 100 mcg with three cohorts of six patients each, with an additional 6-patient expansion cohort at the MTD. ELISA serologic IgM and IgG responses for each antigen was defined as positive response if antibody titers were ≥1:80 over the respective patient’s pre-vaccination serum. The study would be considered positive if at least four of 12 patients treated at the MTD showed immune responses for at least three of the five antigens. Twenty-four patients (median age, 54 years [range, 36–68] were included in the safety analysis. Histology was high-grade serous in 22 patients (92%; 18 had stage III and six stage IV disease. The vaccine was well-tolerated at all doses, with no DLTs. At the highest treated dose, IgG and/or IgM responses were recorded against ≥3 antigens in 9/12 patients (75%, ≥4 in 7/12 (58%, and 5 in 3/12 (25%. With a median follow-up of 19 months (range, 2–39, 20 patients (83% recurred and six (25% died. The unimolecular pentavalent vaccine construct was shown to be safe and immunogenic. Such a construct greatly simplifies regulatory requirements and manufacturing, facilitates scalability, and provides adaptability.

  19. Vaccine-based clinical trials in ovarian cancer

    NARCIS (Netherlands)

    Leffers, Ninke; Daemen, Toos; Boezen, H. Marike; Melief, Kees J. M.; Nijman, Hans W.

    2011-01-01

    Ovarian cancer vaccines are one of the new treatment strategies under investigation in epithelial ovarian cancer. This article discusses the results of different immunization strategies, points out potential pitfalls in study designs and provides possible solutions for augmentation of clinical effic

  20. [Update on current care guidelines: ovarian cancer].

    Science.gov (United States)

    Leminen, Arto; Auranen, Annika; Bützow, Ralf; Hietanen, Sakari; Komulainen, Marja; Kuoppala, Tapio; Mäenpää, Johanna; Puistola, Ulla; Vuento, Maarit; Vuorela, Piia; Yliskoski, Merja

    2012-01-01

    Ovarian cancer is the most lethal gynaecological cancer. It appears that seemingly ovarian or primary peritoneal carcinomas, in fact, originate from fimbriae. BRCA1/2 mutation carriers are recommended for the removal of ovaries and fimbriae, to reduce the risk of cancer. Treatment of epithelial ovarian cancer is based on the combination of surgery and chemotherapy. The residual tumour volume at the primary operation is the most important predictive factor of survival. The best response at the primary treatment is observed with combination chemotherapy with taxane and platinum. Adding bevacitzumab to first line chemotherapy may improve survival.

  1. Ovarian cancer stem cells: Can targeted therapy lead to improved progression-free survival?

    Institute of Scientific and Technical Information of China (English)

    Christen; L; Walters; Haygood; Rebecca; C; Arend; J; Michael; Straughn; Donald; J; Buchsbaum

    2014-01-01

    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.

  2. 绝经前卵巢上皮性癌预后因素分析%Clinical analysis about prognostic factors of the ovarian epithelial cell in cancer premenstrual woman

    Institute of Scientific and Technical Information of China (English)

    林丽红; 郭玉

    2012-01-01

    Objective To investigate prognostic factors of the premenstrual woman with ovarian epithelial cell cancer. Methods From January 2000 to January 2007, the data on 163 cases of patients were collected,and the factors which affected prognosis were retrospectively analyzed. Based on five years of follow-up, the survival rate was compared between layer factors with chi-square test, life method was used in calculation of survival, Kaplan-meier, Log-rank and COX multi-factor mode analytic method was respectively adopted to analyze variables, survival differences and multi-factors analysis. Results The 2-year survival rate was 79.07%, with a 46.01% 5-year survival rate; the cytology grade, residual tumor size and the method of surgery were prognostic factors (P < 0.01) according to the Cox-model multifactor results; based on the COX model multi-factor analysis, cytology classification, residual focal size, the operation method were the independent factors affecting the prognosis (P < 0.01); A statistical significance was found about the 5-year survival rate between every group under a different layer factors by a single factor Logistic regression analysis (P < 0.01). Conclusion The research data shows earlier staging, higher cell differentiation, fewer residual focal size, more optimistic prognosis for the premenstrual epithelial ovarian carcinoma.%目的 探讨影响绝经前卵巢上皮性癌患者生存预后的相关因素.方法 回顾性分析2000年1月~2007年1月共163例绝经前卵巢上皮性癌患者临床资料,评估预后因素.随访时间为5年,各分层因素间生存率比较采用χ2检验,寿命法计算生存率,Kaplan-meier法分析变量,Log-rank法检验生存差异,COX多因素模型进行多因素分析.结果绝经前卵巢上皮性癌患者2年生存率为79.75%,5年生存率为46.01%.单因素逐步COX模型分析与分层因素间生存率比较结果显示:临床分期、病理类型、细胞学分级、残留灶大小、手术方式是

  3. Therapeutic efficacy of TCI chemotherapy regimen for epithelial ovarian cancer and its long- term prognosis%卵巢上皮癌TCI化疗方案的疗效研究及远期预后探讨

    Institute of Scientific and Technical Information of China (English)

    燕纪林

    2012-01-01

    目的 探讨TCI联合化疗方案对于卵巢上皮癌的疗效及远期预后.方法 2000年2月~2010年12月在本院进行规范治疗的卵巢上皮癌158例,运用TCI治疗方案为88例,其化疗方案为TP和值CAP和/或IAP(简称TCI方案);对照组治疗70例,方案选择为PC(环磷酰胺与顺铂),比较两组的临床缓解情况、毒性反应及远期预后,并且对TCI组进行OOX系统回归因素分析.结果 TCI治疗组总体缓解率明显高于对照组,毒性反应方面TCI治疗组的血液系统及神经系统不良反应均显著低于PC组,胃肠道不良反应与心血管系统反应则无显著差异;TCI组5年平均生存率为31.2%,病理分期Ⅰ、Ⅱ、Ⅲ、Ⅳ期中位生存时间分别是79、56、22、18个月,残留灶小于2cm者和治疗次数大于6次者远期预后明显好与相对应者.结论 TCI化疗方案显著优于PC方案,且不良反应相对较少,但胃肠道反应应引起重视,在预后各种因素方面病理分期、术后残留及疗程多少均具有一定相关意义.%Objective To explore the therapeutic efficacy of TCI combined chemotherapy regimen for and its long - term prognosis of epithelial ovarian cancer. Methods A total of 159 patients with epithelial ovarian cancer who received treatments from February 2000 to December 2010 in our hospital were included in the study. Among them, 88 patients were administered with TP and/or CAP and/or IAP regimen (TCI regimen). The control group included 70 patients who were administered with PC (cyclophosphamide and cisplatin). The clinical remission, toxic reactions and long - term prognosis were compared between the two groups. Cox system was applied to the TCI group for regression factor analysis. Results The overall remission was significantly higher in the TCI group than in the control group. In terms of toxic reactions, the adverse reactions of hemato- logical system and nerve system in the TCI group were significantly lower than those in the PC

  4. The expression and significance of PED/PEA-15 and it's phosphorylation state in epithe-lial ovarian tumors%PED/PEA-15及其磷酸化状态在卵巢上皮肿瘤中的表达及意义

    Institute of Scientific and Technical Information of China (English)

    刘记; 金兰; 罗永红

    2016-01-01

    目的::探讨PED/PEA-15( phosphoprotein enriched in diabetes/phosphoprotein enriched in astrocytes)蛋白及其磷酸化状态在卵巢上皮性肿瘤中的表达及临床意义。方法:免疫组化法检测40例卵巢上皮良性肿瘤(良性组)、40例卵巢交界性肿瘤(交界性组)、50例卵巢上皮癌(恶性组)中PED/PEA-15及其磷酸化状态的阳性表达水平。结果:PEA-15蛋白在良性组中表达高于交界性组及恶性组( P0.05)。卵巢癌中PEA-15磷酸化状态pPEA-15-Ser104蛋白表达高于交界性及良性上皮肿瘤(P0.05);另一位点磷酸化状态pPEA-15-Ser116在不同性质卵巢组织、不同年龄、组织学分级、临床分期、淋巴结转移分组中表达无差异( P>0.05)。结论:PEA-15及其磷酸化状态在卵巢癌的发生发展中发挥重要作用,可否通过调控PED/PEA-15的磷酸化状态从而使之成为卵巢癌治疗的重要靶点仍需进一步研究。%Objective:To investigate the expression and clinical significance of PED/PEA-15 protein and its phosphorylation state in epithelial ovarian tumors. Methods:The posi-tive expression level of PED/PEA-15 and it's phosphorylation state in 40 cases of epithelial be-nign ovarian tumor,40 cases of epithelial ovarian borderline tumors and 50 cases of epithelial o-varian cancer was analyzed by immunohistochemical method. Results:The expression of PEA-15 protein in the benign group was higher than that in the borderline group and the malignant group (P0 . 05 ) . There were no significant differences in the expression of pPEA-15-Ser116 in different ovarian tissues,in differ-ent age,histological grade,clinical stage and lymph node metastasis (P>0. 05). Conclusion:PEA-15 and it's phosphorylation state play an important role in the occurrence and development of ovarian cancer. Whether the regulation of phosphorylation status of PED/PEA-15 can be used as an effective therapeutic marker in ovarian epithelial malignant tumor is still need to be

  5. Ovarian cancer immunotherapy: opportunities, progresses and challenges

    Directory of Open Access Journals (Sweden)

    Stevens Richard

    2010-02-01

    Full Text Available Abstract Due to the low survival rates from invasive ovarian cancer, new effective treatment modalities are urgently needed. Compelling evidence indicates that the immune response against ovarian cancer may play an important role in controlling this disease. We herein summarize multiple immune-based strategies that have been proposed and tested for potential therapeutic benefit against advanced stage ovarian cancer. We will examine the evidence for the premise that an effective therapeutic vaccine against ovarian cancer is useful not only for inducing remission of the disease but also for preventing disease relapse. We will also highlight the questions and challenges in the development of ovarian cancer vaccines, and critically discuss the limitations of some of the existing immunotherapeutic strategies. Finally, we will summarize our own experience on the use of patient-specific tumor-derived heat shock protein-peptide complex for the treatment of advanced ovarian cancer.

  6. Clinical observation and therapeutic evaluation of intravenous pump of recombinant human endostatin combined with TP regimen in treating patients with advanced ovarian cancer

    Institute of Scientific and Technical Information of China (English)

    Chi Zhang; Wen-Ying Deng; Ning Li; Su-Xia Luo

    2015-01-01

    Objectives: To observe the curative effects and adverse reactions of recombinant human (rh)-endostatin injection combined with a TP regimen for treating patients with advanced ovarian cancer.Methods: Fifty-four patients with pathologically confirmed ovarian cancer were randomly divided into a combined treatment (intravenous pump of rh-endostatin + TP regimen) group and a control (single chemotherapy) group, twenty-seven patients in each group.All patients were given a conventional CT examination.The level of vascular endothelial growth factor (VEGF), the size of tumor before treatment, after 2 cycles and after 4 cycles of treatment were determined for the comparison of curative effects and adverse reactions.Results: The effective rate was 37.0% (10/27) and disease control rate was 63.0% (17/27) in the combined treatment group after 2 cycles of treatment.The effective rate was 25.9% (7/27) and disease control rate was 63.0% (17/27) in the control group.The comparison between these two groups showed no significant differences (P > 0.05).The effective rate was 63.0% (17/27) and disease control rate was 92.6% (25/27) in the combined treatment group after 4 cycles of treatment.The effective rate was 29.6% (8/27) and disease control rate was 63.0% (17/27) in the control group.The effective rate and disease control rate between these two groups after 4 cycles of treatment showed significant differences (P < 0.05).The incidences of cardiovascular toxicity, myelosuppression, sore muscles and joints, alopecia and gastrointestinal reaction was not significantly different between two groups (P > 0.05).Conclusion: The pump delivery of rh-endostatin can down-regulate the expression of VEGF in ovarian cancer and has the better curative effect and slighter adverse reactions.Copyright 2015, Chinese Medical Association Production.Production and hosting by Elsevier B.V.on behalf of KeAi Communications Co., Ltd.This is an open access article under the CC BY

  7. No stone left unturned: challenges encountered during recruitment of women with advanced ovarian cancer for a phase I study.

    Science.gov (United States)

    Albrecht, Tara A; Taylor, Ann Gill

    2013-11-01

    The recruitment and accrual of participants for cancer clinical trial research is often challenging. Chronic low accrual rates negatively influence the findings and generalizability that can be drawn from the available pool of research. There is a need for further evidence regarding both unsuccessful and successful approaches and useful strategies that investigators have used to counter common recruitment challenges. During recruitment for an intervention study examining the safety, efficacy, and feasibility of a potentially novel supportive therapy, a variety of steps were taken to avoid and subsequently overcome potential and real recruitment challenges the investigators faced. In this article the authors provide an overview of common recruitment challenges as well as the actual challenges encountered, procedures and strategies implemented to counter these challenges, while investigating the combined intervention of flaxseed oil, fasting, caffeine, and exercise in women with recurrent or multi-drug resistant stage III or IV ovarian cancer.

  8. 卵巢交界性肿瘤及Ⅰ期上皮性卵巢癌143例临床分析%Clinical characteristics of borderline ovarian tumors and stage Ⅰ epithelial ovarian cancer: an analysis of 143 cases

    Institute of Scientific and Technical Information of China (English)

    赵旸; 王悦; 沈丹华; 宋荣娜; 许琦; 李艺; 崔恒; 唐军; 魏丽惠

    2011-01-01

    Objective : To study the clinical pathological characteristics and high risk factors for borderline ovarian tumor ( BOT) and stage Ⅰ epithelial ovarian cancer ( EOC). Methods: A total of 91 patients with BOT and 52 patients with stage Ⅰ EOC who were diagnosed and treated in the Department of Gynecology , Peking University People ' s Hospital from November 2002 to May 2010 were recruited in this study. The patients' clinical characteristics were reviewed respectively and compared between the two groups. Results: The women in BOT group were significantly younger than those in EOC group(41. 16 ± 14.95 vs. 50.90 ± 14. 37,P <0. 01). Compared with women with BOT, women with EOC were more likely to be post-menopausal(42.3% vs. 23. 1% ,P =0.016) and more with family history of malignant tumors (26. 9% vs. 13. 2% ,P = 0. 04 ) . There were no significant differences in the size of tumors and the serum level of tumor markers. But the size of solid portion of the tumor of EOC was significantly larger than that of BOT( P <0. 01 ) . The extent of the increase of CP2 among the patients with EOC was higher than that among the patients with BOT( 256. 99 vs. 116. 59 , P = 0. 028) . There was a statistically significant difference between the two groups in tumors ' histopathological type ( P < 0. 01 ) . The serous and mucous tumors were more common in EOC group (90. 1% , 82/91). In contrary, endometrioid, clear cells and mixed epithelial cancers were more common in EOC group than serous and mucous cancers (44.2% , 23/52). Conclusion: Although the clinical presentation of patients with stage Ⅰ EOC was similar to that of those with BOT, there were significant differences in the patients' age, post-menopausal or not, family history of malignant tumors, size of solid portion of tumors, extent of the increase of the tumor biomarker, especially of CP2 and tumors histopathological type. These clinicopathological characteristics might be helpful for us to make

  9. M2型肿瘤相关巨噬细胞在上皮性卵巢癌中的检测%Detection of M2-polarized tumor-associated macrophages in human epithelial ovarian cancer

    Institute of Scientific and Technical Information of China (English)

    杨小荣; 高国兰; 朱亚飞

    2011-01-01

    目的:探讨M2型肿瘤相关巨噬细胞(TAMs)在上皮性卵巢癌组织中的分布,及其与临床病理特征及淋巴管(LV)生成的关系.方法:本研究共纳入74例样本,41例卵巢癌为实验组,18例交界性及15例良性肿瘤为对照组,采用免疫组化方法,用CD68标记巨噬细胞(CD68+)、CD163标记M2型TAMs( CD163+)、D2-40标记LV,了解其在实验组和对照组的分布,及与卵巢癌临床病理特征的关系.结果:卵巢癌组CD68+细胞数、CD163+细胞数、LV数均多于交界性和良性肿瘤组(P<0.01).CD68+细胞分布于癌巢和癌间质,CD163+细胞和LV主要分布于癌间质,癌间质中三者数量明显多于癌巢(P<0.01).癌巢和癌间质中CD68+、CD163+细胞数及癌间质LV数与临床分期、组织学分化、病理类型、手术切缘累及淋巴结转移有关(P<0.01).癌间质LV数与CD68+和CD163+细胞数相关(r=0.759,P<0.01;r=0.888,P<0.01).结论:卵巢癌组织中rAMs主要为M2型,主要分布于癌间质.其细胞数与肿瘤的临床分期、组织分化、病理类型、手术切缘累及和淋巴结转移有关,提示TAMs可能通过促进淋巴管生成,利于肿瘤的淋巴转移.%Objective:To investigate the distribution of M2-Polarized tumor-associated macrophages(TAMs)in human epithelial ovarian cancer as well as its correlation with clinical pathological features and lymphangiogenesis. Methods: Seventy-four samples were enrolled in this study,including 41 samples of patients diagnosed with ovarian cancer as the experimental group, 18 samples with borderline ovarian tumors and 15 samples with benign ovarian tumors as the control group. We used CD68 to mark macrophages and GDI 63 to mark M2-polarized TAMs as well as D2-40 to mark lymphatic vessels( LV) in immunohistochemistry study,to explore the correlation between macrophages distribution and clinical pathological features in these samples. Result:CD68 positive macrophages were detected in both tumor islets and stroma

  10. Subtypes of Ovarian Cancer and Ovarian Cancer Screening

    Science.gov (United States)

    Koshiyama, Masafumi; Matsumura, Noriomi; Konishi, Ikuo

    2017-01-01

    Ovarian cancer is the foremost cause of gynecological cancer death in the developed world, as it is usually diagnosed at an advanced stage. In this paper we discuss current issues, the efficacy and problems associated with ovarian cancer screening, and compare the characteristics of ovarian cancer subtypes. There are two types of ovarian cancer: Type I carcinomas, which are slow-growing, indolent neoplasms thought to arise from a precursor lesion, which are relatively common in Asia; and Type II carcinomas, which are clinically aggressive neoplasms that can develop de novo from serous tubal intraepithelial carcinomas (STIC) and/or ovarian surface epithelium and are common in Europe and the USA. One of the most famous studies on the subject reported that annual screening using CA125/transvaginal sonography (TVS) did not reduce the ovarian cancer mortality rate in the USA. In contrast, a recent study in the UK showed an overall average mortality reduction of 20% in the screening group. Another two studies further reported that the screening was associated with decreased stage at detection. Theoretically, annual screening using CA125/TVS could easily detect precursor lesions and could be more effective in Asia than in Europe and the USA. The detection of Type II ovarian carcinoma at an early stage remains an unresolved issue. The resolving power of CA125 or TVS screening alone is unlikely to be successful at resolving STICs. Biomarkers for the early detection of Type II carcinomas such as STICs need to be developed. PMID:28257098

  11. Ovarian Cancer

    Science.gov (United States)

    ... the ovary, fallopian tube, and peritoneum: Epidemiology and risk factors. http://www.uptodate.com/home. Accessed Feb. 18, 2014. Havrilesky LJ, et al. Oral contraceptive pills as primary prevention for ovarian cancer: A systematic ...

  12. Ovarian Cancer: The Interplay of Lifestyle and Genes

    NARCIS (Netherlands)

    Braem, M.G.M.

    2014-01-01

    Ovarian cancer is a highly lethal disease that is mostly diagnosed at an advanced stage. In Europe, only 36% of women with ovarian cancer can expect to survive 5 years. While our knowledge of ovarian cancer has changed substantially throughout the years, our understanding of its etiology still lacks

  13. Gene Expression Patterns in Ovarian Carcinomas

    Science.gov (United States)

    Schaner, Marci E.; Ross, Douglas T.; Ciaravino, Giuseppe; Sørlie, Therese; Troyanskaya, Olga; Diehn, Maximilian; Wang, Yan C.; Duran, George E.; Sikic, Thomas L.; Caldeira, Sandra; Skomedal, Hanne; Tu, I-Ping; Hernandez-Boussard, Tina; Johnson, Steven W.; O'Dwyer, Peter J.; Fero, Michael J.; Kristensen, Gunnar B.; Børresen-Dale, Anne-Lise; Hastie, Trevor; Tibshirani, Robert; van de Rijn, Matt; Teng, Nelson N.; Longacre, Teri A.; Botstein, David; Brown, Patrick O.; Sikic, Branimir I.

    2003-01-01

    We used DNA microarrays to characterize the global gene expression patterns in surface epithelial cancers of the ovary. We identified groups of genes that distinguished the clear cell subtype from other ovarian carcinomas, grade I and II from grade III serous papillary carcinomas, and ovarian from breast carcinomas. Six clear cell carcinomas were distinguished from 36 other ovarian carcinomas (predominantly serous papillary) based on their gene expression patterns. The differences may yield insights into the worse prognosis and therapeutic resistance associated with clear cell carcinomas. A comparison of the gene expression patterns in the ovarian cancers to published data of gene expression in breast cancers revealed a large number of differentially expressed genes. We identified a group of 62 genes that correctly classified all 125 breast and ovarian cancer specimens. Among the best discriminators more highly expressed in the ovarian carcinomas were PAX8 (paired box gene 8), mesothelin, and ephrin-B1 (EFNB1). Although estrogen receptor was expressed in both the ovarian and breast cancers, genes that are coregulated with the estrogen receptor in breast cancers, including GATA-3, LIV-1, and X-box binding protein 1, did not show a similar pattern of coexpression in the ovarian cancers. PMID:12960427

  14. Rethinking Ovarian Cancer: Recommendations for Improving Outcomes

    OpenAIRE

    2011-01-01

    There have been major advances in our understanding of the cellular and molecular biology of the human malignancies collectively referred to as ovarian cancer. At a recent Helene Harris Memorial Trust meeting, an international group of researchers considered actions that should be taken to improve the outcome for women with ovarian cancer. Nine major recommendations are outlined in this Perspective.

  15. 2种剂型紫杉醇联合卡铂一线治疗晚期卵巢癌的成本-效果分析%Cost-effectiveness Analysis of 2 Dosage Forms of Paclitaxel Combined with Carboplatin for First-line Treatment of Advanced Ovarian Cancer

    Institute of Scientific and Technical Information of China (English)

    王玲欢; 胡家红

    2012-01-01

    目的:评价传统紫杉醇与紫杉醇脂质体联合