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Sample records for advanced ovarian epithelial

  1. Neoadjuvant chemotherapy in advanced epithelial ovarian cancer: A survival study

    Directory of Open Access Journals (Sweden)

    Upasana Baruah

    2015-01-01

    Full Text Available Context: Patients with advanced ovarian cancer have a poor prognosis in spite of the best possible care. Primary debulking surgery has been the standard of care in advanced ovarian cancer; however, it is associated with high mortality and morbidity rates as shown in various studies. Several studies have discussed the benefit of neoadjuvant chemotherapy in patients with advanced ovarian cancer. Aims: This study aims to evaluate the survival statistics of the patients who have been managed with interval debulking surgery (IDS from January 2007 to December 2009. Materials and Methods: During the period from January 2007 to December 2009, a retrospective analysis of 104 patients who underwent IDS for stage IIIC or IV advanced epithelial ovarian cancer at our institute were selected for the study. IDS was attempted after three to five courses of chemotherapy with paclitaxal (175 mg/m 2 and carboplatin (5-6 of area under curve. Overall survival (OS and progression free survival (PFS were compared with results of primary debulking study from existing literature. OS and PFS rates were estimated by means of the Kaplan-Meier method. Results were statistically analyzed by IBM SPSS Statistics 19. Results: The median OS was 26 months and the median PFS was 18 months. In multivariate analysis it was found that both OS and PFS was affected by the stage, and extent of debulking. Conclusions: Neoadjuvant chemotherapy, followed by surgical cytoreduction is a promising treatment strategy for the management of advanced epithelial ovarian cancers.

  2. 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.

  3. Neoadjuvant chemotherapy in advanced epithelial ovarian cancer: A survival study

    OpenAIRE

    Upasana Baruah; Debabrata Barmon; Amal Chandra Kataki; Pankaj Deka; Munlima Hazarika; Bhargab J Saikia

    2015-01-01

    Context: Patients with advanced ovarian cancer have a poor prognosis in spite of the best possible care. Primary debulking surgery has been the standard of care in advanced ovarian cancer; however, it is associated with high mortality and morbidity rates as shown in various studies. Several studies have discussed the benefit of neoadjuvant chemotherapy in patients with advanced ovarian cancer. Aims: This study aims to evaluate the survival statistics of the patients who have been managed with...

  4. Primary Surgery or Interval Debulking for Advanced Epithelial Ovarian Cancer: Does It Matter?

    DEFF Research Database (Denmark)

    Markauskas, A.; Mogensen, O.; Christensen, R. D.;

    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...

  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?

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

    OpenAIRE

    Nikolaou Marinos; Stamenković Srđan; Stergiou Christos; Skarleas Christos; Torrens Michael

    2015-01-01

    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...

  8. Epidemiological overview, advances in diagnosis, prevention, treatment and management of epithelial ovarian cancer in Mexico.

    Science.gov (United States)

    Gallardo-Rincón, Dolores; Espinosa-Romero, Raquel; Muñoz, Wendy Rosemary; Mendoza-Martínez, Roberto; Villar-Álvarez, Susana Del; Oñate-Ocaña, Luis; Isla-Ortiz, David; Márquez-Manríquez, Juan Pablo; Apodaca-Cruz, Ángel; Meneses-García, Abelardo

    2016-04-01

    The epithelial ovarian cancer (EOC) has been underdiagnosed because it does not have a specific clinical presentation, and the signs and symptoms are similar to the irritable bowel syndrome and pelvic inflammatory disease. EOC is less common than breast and cervical cancer, but it is more lethal. On the whole, EOC has an early dissemination to peritoneal cavity, which delays a timely diagnosis and increases the rate of advanced diagnosed disease. The diagnosis usually surprises the women and the primary care physician. Therefore, it is necessary to count on prevention and early diagnosis programs. EOC has 80% response to surgical treatment, but nearly 70% of the patients may relapse in five years. The objectives of this document are presenting a summary of the EOC epidemiology and comment about advancements in prevention, diagnosis, and treatment of this cancer. That will raise awareness about the importance of this disease. PMID:27557390

  9. A prospective comparison of perioperative morbidity in advanced epithelial ovarian cancer: Primary versus interval cytoreduction - experience from India

    OpenAIRE

    Sheikh Zahoor Ahmad; Anupama Rajanbabu; Vijaykumar, D. K.; Altaf Gauhar Haji; Pavithran, K.

    2015-01-01

    Objectives: The objective was to compare perioperative morbidity and mortality of patients with advanced epithelial ovarian cancer (EOC) treated with either of the two treatment approaches; neoadjuvant chemotherapy (NACT) followed by interval debulking versus upfront surgery. Design: Prospective comparative observational study. Participants: In total, 51 patients were included in the study. All patients with diagnosed advanced EOC (International Federation of Gynecology and Obstetrics IIIC an...

  10. Comparative Study on Three Chemotherapeutic Regimens for the Treatment of Advanced Epithelial Ovarian Cancer

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    To investigate the best first-line chemotherapy regimen for the treatment of advanced epithelial ovarian cancer (AEOC), the efficacy of three chemotherapy regimens for treatment of the patients with AEOC in our hospital during Jan. 1992- Jan. 1999 was retrospectively analyzed. The therapeutic effects were compared with the supplement of Melphalan + Hexamethylme (PAM + HMM), cisplatin + adriamycin +cyclophosphamide or isofamide (PAC) or cisplatin + cyclophosphamide or isofamide (PC), Taxol+cisplatin (TP) combined chemotherapy after cytoreductive surgery. The results showed that the overall effective rate of TP was significantly higher than that of PAM+ HMM (P<0. 05); The complete remission rate of TP was significantly higher than that of PAM+ HMM and PAC or PC (all P<0.05);The 2-year survival rate free of tumor of TP was obviously higher than that of PAM+HMM and PAC or PC(all P<0. 05). It was concluded that the therapeutic effect of TP regimen in the treatment of AEOC was better than PAM +HMM and PAC or PC and TP regimen could be recommended currently as the preferred first-line one for the treatment of AEOC.

  11. Evolution of surgery in advanced epithelial ovarian cancer in a dedicated gynaecologic oncology unit—seven year audit from a tertiary care centre in a developing country

    OpenAIRE

    Rajanbabu, Anupama; Kuriakose, Santhosh; Ahmad, Sheikh Zahoor; Khadakban, Tejal; Khadakban, Dhiraj; R. Venkatesan; Vijaykumar, D. K.

    2014-01-01

    Aims To audit our performance as a dedicated gynaecologic oncology unit and to analyse how it has evolved over the years. To retrospectively evaluate the outcome of advanced ovarian cancer treated with neoadjuvant chemotherapy (NACT) followed by interval surgery versus upfront surgery. Methods and results One hundred and ninety-eight patients with advanced epithelial ovarian cancer (EOC) who were treated from 2004 to 2010 were analysed. Eighty-two patients (41.4%) underwent primary surgery an...

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

    Directory of Open Access Journals (Sweden)

    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.

  13. Malnutrition Identified by the Nutritional Risk Index and Poor Prognosis in Advanced Epithelial Ovarian Carcinoma.

    Science.gov (United States)

    Yim, Ga Won; Eoh, Kyung Jin; Kim, Sang Wun; Nam, Eun Ji; Kim, Young Tae

    2016-07-01

    Ovarian cancer is a chronic disease with a risk of malnutrition. Nutritional Risk Index (NRI) has been reported as a simple and accurate tool to assess the nutritional status. We sought to explore the prevalence of malnutrition and its association with survival in ovarian cancer. A retrospective study was conducted in 213 advanced ovarian cancer patients. NRI was calculated before and at the end of treatment using patients' body weight and serum albumin level. Overall survival (OS) and progression-free survival (PFS) were estimated by Kaplan-Meier method, and associations were assessed using a Cox proportional hazards analysis adjusted for known prognostic variables. Moderate to severely malnourished patients had lower 5-yr OS (45.3%) compared to normal to mild group (64.0%), respectively (P = 0.024). Adjusted for covariates, the relative risk of death was 5.8 times higher in moderate/severely malnourished group identified at the last course of chemotherapy (HR = 5.896, 95% CI = 2.723-12.764, P Malnutrition is prevalent among ovarian cancer patients and is found to be a significant predictor for mortality. PMID:27044606

  14. 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.

  15. 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

  16. A prospective comparison of perioperative morbidity in advanced epithelial ovarian cancer: Primary versus interval cytoreduction - experience from India

    Directory of Open Access Journals (Sweden)

    Sheikh Zahoor Ahmad

    2015-01-01

    Full Text Available Objectives: The objective was to compare perioperative morbidity and mortality of patients with advanced epithelial ovarian cancer (EOC treated with either of the two treatment approaches; neoadjuvant chemotherapy (NACT followed by interval debulking versus upfront surgery. Design: Prospective comparative observational study. Participants: In total, 51 patients were included in the study. All patients with diagnosed advanced EOC (International Federation of Gynecology and Obstetrics IIIC and IV presenting for the 1st time were included in the study. Interventions: Patients were either operated upfront (n = 19 if deemed operable or were subjected to NACT followed by interval debulking (n = 32. Primary and Secondary Outcomes: Intra- and postoperative morbidity and mortality were the primary outcome measures. Results: Patients with interval cytoreduction were noted to have significantly lesser operative time, blood loss, and extent of surgery. Their discharge time was also significantly earlier. However, they did not differ from the other group vis. a vis. postoperative complications or mortality. Conclusions: Neoadjuvant chemotherapy although has a positive impact on various intraoperative adverse events, fails to show any impact on immediate postoperative negative outcomes.

  17. Combined therapy with thrombospondin-1 type I repeats (3TSR) and chemotherapy induces regression and significantly improves survival in a preclinical model of advanced stage epithelial ovarian cancer

    OpenAIRE

    Russell, Samantha; Duquette, Mark; Liu, Joyce; Drapkin, Ronny; Lawler, Jack; Petrik, Jim

    2014-01-01

    Most women are diagnosed with epithelial ovarian cancer (EOC) at advanced stage, where therapies have limited effectiveness and the long-term survival rate is low. We evaluated the effects of combined antiangiogenic and chemotherapy treatments on advanced stage EOC. Treatment of EOC cells with a recombinant version of the thrombospondin-1 type I repeats (3TSR) induced more apoptotic cell death (36.5 ± 9.6%) in vitro compared to untreated controls (4.1 ± 1.4). In vivo, tumors were induced in a...

  18. Outcomes of advanced epithelial ovarian cancer with integration of metronomic chemotherapy: An Indian rural cancer centre experience

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    Avinash Pandey

    2016-01-01

    Full Text Available Background: Paclitaxel-platinum and optimal cytoreductive surgery are the standard of care for ovarian carcinoma. Poor socioeconomic profile and therapeutic constraints in rural India poses a therapeutic challenge. Aim: To evaluate outcomes of epithelial ovarian carcinoma. Objectives: To calculate disease-free survival (DFS, overall survival (OS, and factors affecting outcomes. Materials and Methods: Data of patients diagnosed as ovarian carcinoma registered between March 2009 and March 2014 were retrieved. Demographic profile, chemotherapy and response, surgery, and disease progression were collected. Patients who underwent surgery or completed three cycles of chemotherapy were selected. Kaplan-Meir survival was used to determine disease-free and OS. Log-rank test used to evaluate factors affecting outcome. Results: Median follow-up is 26 months. 93/102 patients (91% underwent cytoreductive surgery, of which 37 had primary cytoreduction (40% while 56 had interval cytoreduction. 21/93 (23%, 57/93 (61%, and 15/93 (16% patients were operated by local surgeons, surgeons of our hospital, and trained oncosurgeons, respectively. Induction paclitaxel-platinum was used in 35/63 (56% patients while 28/63 patients (44% received neoadjuvant metronomic chemotherapy. Median DFS and OS are 17 and 54 months respectively while 3 year OS of 66%. Median DFS of patients operated by oncosurgeons versus local surgeons were 22 months versus 15 months (P = 0.01, OS was 54 versus 26 months (P = 0.01.40/88 (45% patients received maintenance metronomic therapy after adjuvant chemotherapy with median of 6 months (range 2-18 months. Patients receiving metronomic maintenance had better DFS, 18 months versus 15 months (P = 0.69. Conclusion: Induction therapy in ovarian carcinoma helps in selecting patients for cytoreductive surgery. Outcomes are better if operated by trained oncosurgeons. Maintenance metronomic has potential to delay disease progression.

  19. Surgical treatment pattern and outcomes in epithelial ovarian cancer patients from a cancer institute in Kerala, India

    OpenAIRE

    Georgeena, P; Rajanbabu, Anupama; Vijaykumar, DK; Pavithran, K.; Sundaram, KR; Deepak, KS; Sanal, MR

    2016-01-01

    Objective To evaluate the treatment and survival pattern of patients with advanced epithelial ovarian cancer. Methods and results Retrospective study of all advanced epithelial ovarian cancer patients treated in the department of gynaecologic oncology from an academic centre, in a four year period from 1 January 2008–31 December 2011. Selection criteria All patients with advanced epithelial ovarian cancer (stage III and IV) who underwent surgery from 2008–2011and had a follow-up of at least t...

  20. Targeted Therapies in Epithelial Ovarian Cancer

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    Jurjees Hasan

    2010-02-01

    Full Text Available Molecularly targeted therapy is relatively new to ovarian cancer despite the unquestionable success with these agents in other solid tumours such as breast and colorectal cancer. Advanced ovarian cancer is chemosensitive and patients can survive several years on treatment. However chemotherapy diminishes in efficacy over time whilst toxicities persist. Newer biological agents that target explicit molecular pathways and lack specific chemotherapy toxicities such as myelosuppression offer the advantage of long-term therapy with a manageable toxicity profile enabling patients to enjoy a good quality of life. In this review we appraise the emerging data on novel targeted therapies in ovarian cancer. We discuss the role of these compounds in the front-line treatment of ovarian cancer and in relapsed disease; and describe how the development of predictive clinical, molecular and imaging biomarkers will define the role of biological agents in the treatment of ovarian cancer.

  1. Targeted Therapies in Epithelial Ovarian Cancer

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    Dean, Emma; El-Helw, Loaie; Hasan, Jurjees, E-mail: jurjees.hasan@christie.nhs.uk [Christie Hospital NHS Foundation Trust / Wilmslow Road, Manchester, M20 4BX (United Kingdom)

    2010-02-23

    Molecularly targeted therapy is relatively new to ovarian cancer despite the unquestionable success with these agents in other solid tumours such as breast and colorectal cancer. Advanced ovarian cancer is chemosensitive and patients can survive several years on treatment. However chemotherapy diminishes in efficacy over time whilst toxicities persist. Newer biological agents that target explicit molecular pathways and lack specific chemotherapy toxicities such as myelosuppression offer the advantage of long-term therapy with a manageable toxicity profile enabling patients to enjoy a good quality of life. In this review we appraise the emerging data on novel targeted therapies in ovarian cancer. We discuss the role of these compounds in the front-line treatment of ovarian cancer and in relapsed disease; and describe how the development of predictive clinical, molecular and imaging biomarkers will define the role of biological agents in the treatment of ovarian cancer.

  2. 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.

  3. Targeted Therapies in Epithelial Ovarian Cancer

    OpenAIRE

    Jurjees Hasan; Loaie El-Helw; Emma Dean

    2010-01-01

    Molecularly targeted therapy is relatively new to ovarian cancer despite the unquestionable success with these agents in other solid tumours such as breast and colorectal cancer. Advanced ovarian cancer is chemosensitive and patients can survive several years on treatment. However chemotherapy diminishes in efficacy over time whilst toxicities persist. Newer biological agents that target explicit molecular pathways and lack specific chemotherapy toxicities such as myelosuppression offer the a...

  4. Fischer 344 Rat: A Preclinical Model for Epithelial Ovarian Cancer Folate-Targeted Therapy.

    OpenAIRE

    AZAIS, Henri; QUENIAT, Gurvan; Bonner, Caroline; Kerdraon, Olivier; Tardivel, Meryem; Leroux, Bertrand; Frochot, Céline; Betrouni, Nacim; Collinet, Pierre; Mordon, Serge

    2015-01-01

    Objective: Ovarian cancer prognosis remains dire after primary therapy. Recurrence rates are disappointingly high as 60% of women with advanced epithelial ovarian cancer considered in remission will develop recurrent disease within 5 years. Special attention to undetected peritoneal metastasis and residual tumorous cells during surgery is necessary as they are the main predictive factors of recurrences. Folate receptor [alpha] (FR[alpha]) shows promising prospects in targeting ovarian cancero...

  5. Effect of progesterone combined with chemotherapy on epithelial ovarian cancer

    Institute of Scientific and Technical Information of China (English)

    陈晓军; 丰有吉

    2003-01-01

    Objective To identify an effective auxiliary therapy for epithelial ovarian cancer. Methods Progesterone acetate given at 250 mg intramuscularly twice a week for 1 month followed by increased administration to 500 mg intramuscularly every two weeks for 3 years was used in combination with platinum based chemotherapy to treat patients with epithelial ovarian cancer as a first-line therapy. Prognoses of the patients receiving progesterone combined with chemotherapy (progesterone group) and those receiving chemotherapy only (control group) were compared. Results Three-year recurrence and survival conditions of the progesterone and control groups were as follows. Stage Ⅰa: no patient relapsed or died in either group. Stage Ⅰb-Ⅰc: three-year recurrence rates were 14.2% and 37.5%, respectively (P=0.2845); three-year survival rates were 92.3% and 87.5% (P=0.7221). Stage Ⅱ: 1 patient relapsed and died among the 3 patients in the progesterone group; among the 4 patients in the control group, 1 patient relapsed, none died. Stage Ⅲ: three-year recurrence rates were 30.8% and 64.3%, respectively (P=0.1170); three-year survival rates were 85.7% and 42.9%, respectively (P=0.005). Stage Ⅳ: 4 patients relapsed and 1 patient died among the 7 patients in the progesterone group; both the patients in the control group relapsed and died. Conclusions The results indicated that progesterone combined with platinum based chemotherapy as a first-line therapy may improve the prognosis of advanced epithelial ovarian cancer, but would not change the prognosis of early stage epithelial ovarian cancer.

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

    Directory of Open Access Journals (Sweden)

    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.

  7. 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.

  8. Expression and Function of CD44 in Epithelial Ovarian Carcinoma

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    Joelle D. Sacks

    2015-11-01

    Full Text Available CD44, a cell surface glycoprotein, has been increasingly implicated in the pathogenesis and progression of epithelial ovarian cancer, the deadliest gynecologic malignancy in women. Here, we review recent reports on the expression and function of CD44 in epithelial ovarian carcinoma. Further functional data for CD44 in peritoneal adhesion and metastatic progression and its association with stem cells is highlighted. Recent studies utilizing CD44 for therapeutic targeting are also discussed.

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

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    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. 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

  11. Bilateral ovarian mixed epithelial adenocarcinoma in a postmenopausal woman with unilateral ovarian yolk sac tumor component

    OpenAIRE

    Qin CHEN; Chen, Xiaoduan

    2014-01-01

    Ovarian yolk sac tumors (YSTs) usually occur in the young women and have been rarely documented in perimenopausal and postmenopausal women. The different age distribution supposes their complex nomenclature and histogenesis. We report a case of bilateral ovarian epithelial carcinoma with right ovarian YST component in a postmenopausal woman. The patient was treated by surgery and adjuvant combination chemotherapy of taxol and carboplatin for 6 courses and has been clinically free of tumor for...

  12. 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.

  13. 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.

  14. 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.

  15. Ovarian yolk sac tumors in older women arising from epithelial ovarian tumors or with no detectable epithelial component.

    Science.gov (United States)

    Roth, Lawrence M; Talerman, Aleksander; Levy, Tally; Sukmanov, Oleg; Czernobilsky, Bernard

    2011-09-01

    Yolk sac tumor (YST) occurs rarely in older women, either in association with a variety of ovarian epithelial tumors or, considerably less often, without an identifiable epithelial precursor. The patients often have elevated serum levels of α-fetoprotein that roughly correlate with the amount of the YST component. In postmenopausal women with an ovarian mass and elevated serum levels of α-fetoprotein, a tumor of this type should be suspected. Endometrioid carcinoma is the most common putative precursor, and the tumor is often associated with an endometriotic cyst; however, malignant Müllerian mixed tumor and mucinous neoplasms have also been reported as precursors. We report 4 cases of YST in postmenopausal women. Of the 3 cases with an identified epithelial component, 1 was serous carcinoma, another was clear cell adenocarcinoma, and the third was an admixture of endometrioid and clear cell adenocarcinoma arising from an endometriotic cyst. Although a precursor epithelial ovarian neoplasm, typically a malignancy (somatic carcinoma), is usually identified, no precursor neoplasm was observed in 1 of our cases and in 5 cases from the literature. We believe that YSTs in older women, whether or not an epithelial component is detected histologically, constitute a single entity that is distinct from YSTs in younger patients and should be treated aggressively. Neoplasms with a YST component in older women are less responsive to the chemotherapy currently used for ovarian germ cell tumors; therefore, adjuvant therapy should include platinum-based chemotherapy designed to treat both epithelial ovarian cancer and germ cell tumors. Of the 24 reported cases, including our own, 17 died of neoplasms within 25 months and another was living with disease at 2 months. However, 2 more recent patients treated aggressively with platinum-based chemotherapy designed to treat both epithelial and germ cell tumor components with stage 1 disease are living and have been disease free >1

  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. Carboplatin and Paclitaxel With or Without Bevacizumab Compared to Docetaxel, Carboplatin, and Paclitaxel in Treating Patients With Stage II, Stage III, or Stage IV Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cavity Carcinoma (Cancer)

    Science.gov (United States)

    2013-03-18

    Brenner Tumor; Fallopian Tube Cancer; Ovarian Carcinosarcoma; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Epithelial Carcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Undifferentiated Adenocarcinoma; Primary Peritoneal Cavity Cancer; Stage II Ovarian Epithelial Cancer; Stage III Ovarian Epithelial Cancer; Stage IV Ovarian Epithelial Cancer

  18. 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

    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...

  19. Bilateral ovarian mixed epithelial adenocarcinoma in a postmenopausal woman with unilateral ovarian yolk sac tumor component.

    Science.gov (United States)

    Chen, Qin; Chen, Xiaoduan

    2014-01-01

    Ovarian yolk sac tumors (YSTs) usually occur in the young women and have been rarely documented in perimenopausal and postmenopausal women. The different age distribution supposes their complex nomenclature and histogenesis. We report a case of bilateral ovarian epithelial carcinoma with right ovarian YST component in a postmenopausal woman. The patient was treated by surgery and adjuvant combination chemotherapy of taxol and carboplatin for 6 courses and has been clinically free of tumor for 6 months. The correlation between the YST and the epithelial components always confuse us. Ovarian yolk sac tumors are not a discrete entity and represent a multifaceted group of neoplasms. The conjunction of multi antibodies help in differential diagnoses. In addition to a thorough case description, the literature concerning this entity is reviewed and discussed. PMID:25550883

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

    OpenAIRE

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

    2012-01-01

    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...

  2. Predictive and Prognostic Protein Biomarkers in Epithelial Ovarian Cancer: Recommendation for Future Studies

    OpenAIRE

    Le Page, Cécile; David G Huntsman; Provencher, Diane M; Mes-Masson, Anne-Marie

    2010-01-01

    Epithelial ovarian cancer is the most lethal gynecological malignancy. Due to its lack of symptoms, this disease is diagnosed at an advanced stage when the cancer has already spread to secondary sites. While initial rates of response to first treatment is >80%, the overall survival rate of patients is extremely low, mainly due to development of drug resistance. To date, there are no reliable clinical factors that can properly stratify patients for suitable chemotherapy strategies. Clinical pa...

  3. Predictive and Prognostic Protein Biomarkers in Epithelial Ovarian Cancer: Recommendation for Future Studies

    OpenAIRE

    Cécile Le Page; David G Huntsman; Provencher, Diane M; Anne-Marie Mes-Masson

    2010-01-01

    Epithelial ovarian cancer is the most lethal gynecological malignancy. Due to its lack of symptoms, this disease is diagnosed at an advanced stage when the cancer has already spread to secondary sites. While initial rates of response to first treatment is >80%, the overall survival rate of patients is extremely low, mainly due to development of drug resistance. To date, there are no reliable clinical factors that can properly stratify patients for suitable chemotherapy strategies. Clinical...

  4. 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...... improvement. DESIGN: Comparative registry-based study supplemented with data from medical records. SETTING: Six hospitals in Denmark. PARTICIPANTS: Women registered with epithelial ovarian cancer, fallopian tube cancer and borderline ovarian tumor. MAIN OUTCOME MEASURE: Data completeness and strength of...... validity of ovarian cancer data in the DGCD is sufficient for quality monitoring in gynecological oncology....

  5. 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...... improvement. DESIGN: Comparative registry-based study supplemented with data from medical records. SETTING: Six hospitals in Denmark. PARTICIPANTS: Women registered with epithelial ovarian cancer, fallopian tube cancer and borderline ovarian tumor. MAIN OUTCOME MEASURE: Data completeness and strength of...... validity of ovarian cancer data in the DGCD is sufficient for quality monitoring in gynecological oncology Udgivelsesdato: 2009...

  6. Paclitaxel, Bevacizumab And Adjuvant Intraperitoneal Carboplatin in Treating Patients Who Had Initial Debulking Surgery for Stage II, Stage III, or Stage IV Ovarian Epithelial, Primary Peritoneal, or Fallopian Tube Cancer

    Science.gov (United States)

    2014-06-18

    Brenner Tumor; Fallopian Tube Cancer; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Epithelial Carcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Undifferentiated Adenocarcinoma; Primary Peritoneal Cavity Cancer; Stage II Ovarian Epithelial Cancer; Stage III Ovarian Epithelial Cancer; Stage IV Ovarian Epithelial Cancer

  7. 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+ ...

  8. 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.

  9. 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.

  10. 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

  11. 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....

  12. Cytologic changes of ovarian epithelial cancer induced by neoadjuvant chemotherapy

    OpenAIRE

    Wang, Yiying; Wang, Yue; Zheng, Wenxin

    2013-01-01

    Objective: Neoadjuvant chemotherapy (NACT) followed by cytoreduction has now become a part of standard care for patients with advanced ovarian cancer. Cytologic changes of the cancer cells induced by NACT, however, sometimes may cause confusion in terms of pathologic diagnosis and therefore inappropriate management. The objective of this study was to characterize the histologic or cytologic features of the ovarian cancers from those patients who received NACT in order to improve the diagnosti...

  13. Different Imprinting Status of IGF-2 in Epithelial Ovarian Tumors

    Institute of Scientific and Technical Information of China (English)

    熊雅丽; 孙永玉; 李红发

    2002-01-01

    Summary: To explore whether the imprinting status of IGF-2 in the malignant epithelial ovarian tumors is different from that in benign tumors, the target sequences (DNA and RNA) which contain a polymorphism site for ApaI restriction endonuclease digestion were amplified with PCR and RT-PCR methods. Then the PCR/RT-PCR products were digested by ApaI. The IGF-2 transcriptional pattern came out from the results of endonucleases digestion. Among the 36 cases of benign epithelial ovarian tumors, 20 were heterozygous for ApaI locus and all showed genomic imprinting. While in the malignant group, 22 were heterozygous for ApaI locus but six were found to lose imprinting. Significant differences existed between the two groups (P<0. 05). Loss of imprinting of IGF-2 may serve as a marker for differentiating the malignant ovarian cancers from the benign ones. In a new field of molecular genetics, our research provides an experimental basis for genetic diagnosis and treatment of the ovarian cancers.

  14. 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.

  15. 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

  16. 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.

  17. Treatment Strategy for Recurrent and Refractory Epithelial Ovarian Cancer: Efficacy of High-Dose Chemotherapy with Hematopoietic Stem Cell Transplantation

    OpenAIRE

    Muramatsu, Toshinari; Shinozuka, Takao; Hirasawa, Takeshi; Tsukada, Hitomi; Maeda, Hironobu; Miyamoto, Tsuyoshi; Murakami, Masaru; Kajiwara, Hiroshi; Yasuda, Masanori; Osamura, R. Yoshiyuki; Mikami, Mikio

    2006-01-01

    According to population statistics in Japan, approximately 3,800 women die of ovarian ­cancer annually, and approximately 6,000 are affected by this disease. Ovarian cancer is ­referred to as a “silent tumor”, since patients have few subjective symptoms and by the time symptoms are observed, the cancer has progressed to Stage III or IV in about half of the patients. The basic treatment for advanced epithelial ovarian cancer is to remove as much of the tumor as possible, and subsequently to pe...

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. 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

  3. 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

  4. Recent Technological Advances in Using Mouse Models to Study Ovarian Cancer

    OpenAIRE

    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 ...

  5. Epidemiologic and molecular characteristics of borderline and malignant epithelial ovarian tumors

    Science.gov (United States)

    Bastos, Eugenia Maria Chaves De Moraes

    Data from the Cancer and Steroid Hormone Study, a multicenter, population-based, case-control study were used to identify risk factors for epithelial ovarian cancer according to tumor behavior, histologic types, as well as p53 expression. Cases were women between 20 to 54 years old diagnosed with epithelial ovarian cancer from 1980 to 1982. Controls were women selected by random digit dialing. Tumor samples were analyzed for p53 overexpression using immunohistochemistry. Case-case and case-control conditional logistic regression models matched on age and diagnosing centers were used to calculate odds ratios (OR's) and 95% confidence intervals (CI's) for borderline, malignant, mucinous, and nonmucinous tumors, and p53 positive and p53 negative cases. The OR's for high number of lifetime ovulatory cycles (376-533 compared with less than 234) were 3.1 (95% CI 1.6-6.1) for malignant and 1.4 (95% CI 0.5-3.7) for borderline cases. The high number of ovulatory cycles was also a strong risk factor among nonmucinous cases. OR's for current and recent ex-smokers compared with never smokers were 2.8 (95% CI 1.7-4.8) for mucinous and 0.9 (95% CI 0.7-1.1) for nonmucinous types. Infertility showed a positive association with borderline ovarian cancer. Family history of ovarian or breast cancer was positively associated with malignant and nonmucinous cases. Parity had an inverse association with malignant ovarian cancer cases. When cases were subdivided by p53 results, the OR for tobacco smoking and p53 positive ovarian cancer was elevated for mucinous (OR = 3.9; 95% CI 0.8-18) at localized stage. Alcohol use showed a positive association with p53 positive malignant cases at advanced stage (OR = 2.0; 95% CI 1.2-3.2) and with p53 positive nonmucinous cases at advanced stage (OR = 2.1; 95% CI 1.2-3.4). A positive association between high number of ovulatory cycles and p53 positive malignant cases was observed in cases with localized stage (OR = 6.6; 95% CI 1.0-45) and advanced

  6. Changes of TIZ expression in epithelial ovarian cancer cells

    Institute of Scientific and Technical Information of China (English)

    Huan-Yu Zheng; Hong-Yu Zheng; Yun-Tao Zhou; En-Ling Liu; Jie Li; Yan-Mei Zhang

    2015-01-01

    Objective:To study the change ofTIZ expression in epithelial ovarian cancer cells.Methods:HO8910 cells were transinfected with siRNA to inhibit the expression ofTIZ. pcDNA3.1-TIZ vectors were combined to increase theTIZ expression level.The cell viability, colony forming efficiency and cycle distribution ofHO8910,HO8910/NC,HO8910/pcDNA3.1-NC,HO8910/TIZ-573 andHO8910/pcDNA3.1-TIZ were compared, and the invasion rate, migration rate and adhesion rate between5 groups of cells were compared.Results:Compared with those ofHO8910,HO8910/NC andHO8910/pcDNA3.1-NC, the cell viability, colony forming efficiency and cell cycle distribution ofHO8910/TIZ-573 were increased, while the indexes ofHO8910/pcDNA3.1-NC were decreased with statistical significant difference(P0.05). Conclusions:The expression ofTIZ can inhibit the proliferation of epithelial ovarian cancer cells.

  7. 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...

  8. 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...

  9. 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.

  10. Predictive and Prognostic Protein Biomarkers in Epithelial Ovarian Cancer: Recommendation for Future Studies

    Directory of Open Access Journals (Sweden)

    Cécile Le Page

    2010-05-01

    Full Text Available Epithelial ovarian cancer is the most lethal gynecological malignancy. Due to its lack of symptoms, this disease is diagnosed at an advanced stage when the cancer has already spread to secondary sites. While initial rates of response to first treatment is >80%, the overall survival rate of patients is extremely low, mainly due to development of drug resistance. To date, there are no reliable clinical factors that can properly stratify patients for suitable chemotherapy strategies. Clinical parameters such as disease stage, tumor grade and residual disease, although helpful in the management of patients after their initial surgery to establish the first line of treatment, are not efficient enough. Accordingly, reliable markers that are independent and complementary to clinical parameters are needed for a better management of these patients. For several years, efforts to identify prognostic factors have focused on molecular markers, with a large number having been investigated. This review aims to present a summary of the recent advances in the identification of molecular biomarkers in ovarian cancer patient tissues, as well as an overview of the need and importance of molecular markers for personalized medicine in ovarian cancer.

  11. Sargramostim and Paclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Patients With Advanced Ovarian Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer That Did Not Respond to Previous Chemotherapy

    Science.gov (United States)

    2014-01-15

    Brenner Tumor; Fallopian Tube Cancer; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Epithelial Carcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Undifferentiated Adenocarcinoma; Peritoneal Cavity Cancer; Recurrent Ovarian Epithelial Cancer; Stage III Ovarian Epithelial Cancer; Stage IV Ovarian Epithelial Cancer

  12. Prognostic Value of Residual Disease after Interval Debulking Surgery for FIGO Stage IIIC and IV Epithelial Ovarian Cancer

    OpenAIRE

    Rutten, Marianne J.; Sonke, Gabe S; Westermann, Anneke M.; van Driel, Willemien J.; Trum, Johannes W.; Kenter, Gemma G.; Marrije R. Buist

    2015-01-01

    Although complete debulking surgery for epithelial ovarian cancer (EOC) is more often achieved with interval debulking surgery (IDS) following neoadjuvant chemotherapy (NACT), randomized evidence shows no long-term survival benefit compared to complete primary debulking surgery (PDS). We performed an observational cohort study of patients treated with debulking surgery for advanced EOC to evaluate the prognostic value of residual disease after debulking surgery. All patients treated between 1...

  13. DNA methylation profiles of ovarian epithelial carcinoma tumors and cell lines.

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    Sahar Houshdaran

    Full Text Available BACKGROUND: Epithelial ovarian carcinoma is a significant cause of cancer mortality in women worldwide and in the United States. Epithelial ovarian cancer comprises several histological subtypes, each with distinct clinical and molecular characteristics. The natural history of this heterogeneous disease, including the cell types of origin, is poorly understood. This study applied recently developed methods for high-throughput DNA methylation profiling to characterize ovarian cancer cell lines and tumors, including representatives of three major histologies. METHODOLOGY/PRINCIPAL FINDINGS: We obtained DNA methylation profiles of 1,505 CpG sites (808 genes in 27 primary epithelial ovarian tumors and 15 ovarian cancer cell lines. We found that the DNA methylation profiles of ovarian cancer cell lines were markedly different from those of primary ovarian tumors. Aggregate DNA methylation levels of the assayed CpG sites tended to be higher in ovarian cancer cell lines relative to ovarian tumors. Within the primary tumors, those of the same histological type were more alike in their methylation profiles than those of different subtypes. Supervised analyses identified 90 CpG sites (68 genes that exhibited 'subtype-specific' DNA methylation patterns (FDR<1% among the tumors. In ovarian cancer cell lines, we estimated that for at least 27% of analyzed autosomal CpG sites, increases in methylation were accompanied by decreases in transcription of the associated gene. SIGNIFICANCE: The significant difference in DNA methylation profiles between ovarian cancer cell lines and tumors underscores the need to be cautious in using cell lines as tumor models for molecular studies of ovarian cancer and other cancers. Similarly, the distinct methylation profiles of the different histological types of ovarian tumors reinforces the need to treat the different histologies of ovarian cancer as different diseases, both clinically and in biomarker studies. These data

  14. Dietary fat intake and risk of epithelial ovarian cancer by tumour histology

    OpenAIRE

    Merritt, M. A.; Cramer, D. W.; Missmer, S.A.; Vitonis, A.F.; Titus, L.J.; Terry, K. L.

    2014-01-01

    Background: Studies of fat intake and epithelial ovarian cancer (EOC) risk have reported inconsistent findings, hence we hypothesised that associations may vary by histologic subtype. Methods: We evaluated fat intake in a New England case–control study including 1872 cases and 1978 population-based controls (1992–2008). Epithelial ovarian cancer risk factors and diet were assessed using a food frequency questionnaire at enrolment. Logistic regression was used to estimate associations between ...

  15. Genetic Polymorphisms in the Paraoxonase 1 Gene and Risk of Ovarian Epithelial Carcinoma

    OpenAIRE

    Lurie, Galina; Wilkens, Lynne R.; Pamela J Thompson; McDuffie, Katharine E.; Carney, Michael E; Terada, Keith Y.; Goodman, Marc T.

    2008-01-01

    Oxidative stress during successive ovulations increases the opportunity for DNA damage to ovarian epithelial cells and the potential for malignant transformation. Paraoxonase 1 (PON1) is an endogenous free radical scavenger that reduces oxidative stress. The association of two common functional single nucleotide polymorphisms (SNP), rs854560 T>A and rs662 A>G, with the risk of epithelial ovarian cancer was examined in a population-based case-control study in Hawaii. A personal interview and b...

  16. 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

    BACKGROUND: ATP-binding cassette (ABC) transporters play various roles in cancer biology and drug resistance, but their association with outcomes in serous epithelial ovarian cancer (EOC) is unknown. METHODS: The relationship between clinical outcomes and ABC transporter gene expression in two...... 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....

  17. Hormonal and Reproductive Risk Factors for Epithelial Ovarian Cancer by Tumor Aggressiveness

    OpenAIRE

    Poole, Elizabeth M.; Merritt, M. A.; Jordan, S.J.; Yang, H P; Hankinson, Susan Elizabeth; Park, Y; Rosner, Bernard Alfred; Webb, P M; Cramer, Daniel William; Wentzensen, N; Terry, Kathryn Lynne; Tworoger, Shelley Slate

    2013-01-01

    Background Approximately half of epithelial ovarian cancers are fatal within three years; however about 35% of women survive at least ten years. In the Nurses’ Health Study, New England Case-Control Study, Australian Ovarian Cancer Study, and NIH-AARP Diet and Health Study, we investigated potential differences in the associations with ovarian cancer risk factors by tumor aggressiveness, defined based on time from diagnosis until death. Methods We calculated relative risks (RR) an...

  18. Drugs with potential chemopreventive properties in relation to epithelial ovarian cancer--a nationwide case-control study.

    Science.gov (United States)

    Baandrup, Louise

    2015-07-01

    Ovarian cancer has a poor prognosis because the disease in the majority of patients is diagnosed at an advanced stage as a result of nonspecific symptoms and lack of efficient screening methods. Because of the poor prognosis of ovarian cancer and the challenge of early detection of the disease, identification of protective factors is important. It has been suggested that some commonly used drugs may have a protective effect against cancer, including ovarian cancer; however, the literature on chemopreventive measures for ovarian cancer is sparse and the results are inconclusive. Most previous studies have substantial methodological constraints, including limited study size and self-reporting of drug use, which introduces potential recall bias and misclassification. This PhD thesis includes a nationwide case-control study to evaluate associations between use of drugs with potential chemopreventive properties and risk of epithelial ovarian cancer. The study is nested in the entire Danish female population using data from the following nationwide registries: the Danish Cancer Registry, the Danish Civil Registration System, the Danish Prescription Registry, the Danish National Patient Register, and registries in Statistics Denmark on fertility, education, and income. Information from the included registries is linked by use of the unique personal identification number assigned to all Danish citizens. The cases were all women in Denmark with epithelial ovarian cancer diagnosed during 2000-2009 (Paper 1) and 2000-2011 (Papers 2 and 3), identified in the Cancer Registry. Age-matched female population controls were randomly selected from the Civil Registration System by risk-set sampling. We required that cases and controls have no history of cancer (except non-melanoma skin cancer) and that controls not previously have undergone bilateral oophorectomy or salpingo-oophorectomy. The total study population comprised 3741 epithelial ovarian cancer cases and 50,576 controls in

  19. 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

  20. The comparison of glycosphingolipids isolated from an epithelial ovarian cancer cell line and a nontumorigenic epithelial ovarian cell line using MALDI-MS and MALDI-MS/MS.

    Science.gov (United States)

    Rajanayake, Krishani K; Taylor, William R; Isailovic, Dragan

    2016-08-01

    Glycosphingolipids (GSLs) are important biomolecules, which are linked to many diseases such as GSL storage disorders and cancer. Consequently, the expression of GSLs may be altered in ovarian cancer cell lines in comparison to apparently healthy cell lines. Here, differential expressions of GSLs in an epithelial ovarian cancer cell line SKOV3 and a nontumorigenic epithelial ovarian cell line T29 were studied using matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) and MALDI-MS/MS. The isolation of GSLs from SKOV3 and T29 cell lines was carried out using Folch partition. GSLs were successfully detected by MALDI-MS, and structurally assigned by a comparison of their MALDI-MS/MS fragmentation patterns with MS/MS data found in SimLipid database. Additionally, LIPID MAPS was used to assign GSL ion masses in MALDI-MS spectra. Seventeen neutral GSLs were identified in Folch partition lower (chloroform/methanol) phases originating from both cell lines, while five globo series neutral GSLs were identified only in the Folch partition lower phase of SKOV3 cell line. Several different sialylated GSLs were detected in Folch partition upper (water/methanol) phases of SKOV3 and T29 cell lines. Overall, this study demonstrates the alteration and increased glycosylation of GSLs in an epithelial ovarian cancer cell line in comparison to a nontumorigenic epithelial ovarian cell line. PMID:27267063

  1. Neoadjuvant chemotherapy versus primary surgery in advanced ovarian carcinoma

    Directory of Open Access Journals (Sweden)

    Elshamy Maged R

    2005-08-01

    Full Text Available Abstract Background Patients with advanced ovarian cancer should be treated by radical debulking surgery aiming at complete tumor resection. Unfortunately about 70% of the patients present with advanced disease, when optimal debulking can not be obtained, and therefore these patients gain little benefit from surgery. Neoadjuvant chemotherapy (NACT has been proposed as a novel therapeutic approach in such cases. In this study, we report our results with primary surgery or neoadjuvant chemotherapy as treatment modalities in the specific indication of operable patients with advanced ovarian carcinoma (no medical contraindication to debulking surgery. Patients and methods A total of 59 patients with stage III or IV epithelial ovarian carcinomas were evaluated between 1998 and 2003. All patients were submitted to surgical exploration aiming to evaluate tumor resectability. Neoadjuvant chemotherapy was given (in 27 patients where optimal cytoreduction was not feasible. Conversely primary debulking surgery was performed when we considered that optimal cytoreduction could be achieved by the standard surgery (32 patients. Results Optimal cytoreduction was higher in the NACT group (72.2% than the conventional group (62.4%, though not statistically significant (P = 0.5. More important was the finding that parameters of surgical aggressiveness (blood loss rates, ICU stay and total hospital stay were significantly lower in NACT group than the conventional group. The median overall survival time was 28 months in the conventional group and 25 months in NACT group with a P value of 0.5. The median disease free survival was 19 months in the conventional group and 21 months in NACT group (P = 0.4. In multivariate analysis, the pathologic type and degree of debulking were found to affect the disease free survival significantly. Overall survival was not affected by any of the study parameters. Conclusion Primary chemotherapy followed by interval debulking surgery

  2. Neoadjuvant chemotherapy in advanced ovarian cancer: latest results and place in therapy

    OpenAIRE

    Sato, Seiya; Itamochi, Hiroaki

    2014-01-01

    Approximately 70% of women with epithelial ovarian cancer (EOC) are diagnosed with advanced stage disease, which is associated with high morbidity and mortality. The standard approach to treating patients with advanced EOC remains primary debulking surgery (PDS) followed by chemotherapy. EOC is one of the most sensitive of all solid tumors to cytotoxic drugs, with over 80% of women showing a response to standard chemotherapy combined with taxane and platinum. Furthermore, residual disease is ...

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

    Science.gov (United States)

    Cuellar-Partida, Gabriel; Lu, Yi; Dixon, Suzanne C; Fasching, Peter A; Hein, Alexander; Burghaus, Stefanie; Beckmann, Matthias W; Lambrechts, Diether; Van Nieuwenhuysen, Els; Vergote, Ignace; Vanderstichele, Adriaan; Doherty, Jennifer Anne; Rossing, Mary Anne; Chang-Claude, Jenny; Rudolph, Anja; Wang-Gohrke, Shan; Goodman, Marc T; Bogdanova, Natalia; Dörk, Thilo; Dürst, Matthias; Hillemanns, Peter; Runnebaum, Ingo B; Antonenkova, Natalia; Butzow, Ralf; Leminen, Arto; Nevanlinna, Heli; Pelttari, Liisa M; Edwards, Robert P; Kelley, Joseph L; Modugno, Francesmary; Moysich, Kirsten B; Ness, Roberta B; Cannioto, Rikki; Høgdall, Estrid; Høgdall, Claus; Jensen, Allan; Giles, Graham G; Bruinsma, Fiona; Kjaer, Susanne K; Hildebrandt, Michelle A T; Liang, Dong; Lu, Karen H; Wu, Xifeng; Bisogna, Maria; Dao, Fanny; Levine, Douglas A; Cramer, Daniel W; Terry, Kathryn L; Tworoger, Shelley S; Stampfer, Meir; Missmer, Stacey; Bjorge, Line; Salvesen, Helga B; Kopperud, Reidun K; Bischof, Katharina; Aben, Katja K H; Kiemeney, Lambertus A; Massuger, Leon F A G; Brooks-Wilson, Angela; Olson, Sara H; McGuire, Valerie; Rothstein, Joseph H; Sieh, Weiva; Whittemore, Alice S; Cook, Linda S; Le, Nhu D; Blake Gilks, C; Gronwald, Jacek; Jakubowska, Anna; Lubiński, Jan; Kluz, Tomasz; Song, Honglin; Tyrer, Jonathan P; Wentzensen, Nicolas; Brinton, Louise; Trabert, Britton; Lissowska, Jolanta; McLaughlin, John R; Narod, Steven A; Phelan, Catherine; Anton-Culver, Hoda; Ziogas, Argyrios; Eccles, Diana; Campbell, Ian; Gayther, Simon A; Gentry-Maharaj, Aleksandra; Menon, Usha; Ramus, Susan J; Wu, Anna H; Dansonka-Mieszkowska, Agnieszka; Kupryjanczyk, Jolanta; Timorek, Agnieszka; Szafron, Lukasz; Cunningham, Julie M; Fridley, Brooke L; Winham, Stacey J; Bandera, Elisa V; Poole, Elizabeth M; Morgan, Terry K; Goode, Ellen L; Schildkraut, Joellen M; Pearce, Celeste L; Berchuck, Andrew; Pharoah, Paul D P; Webb, Penelope M; Chenevix-Trench, Georgia; Risch, Harvey A; MacGregor, Stuart

    2016-07-01

    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. Recent studies show that certain genetic variants confer susceptibility to all subtypes while other variants are subtype-specific. Here, we perform an extensive analysis of the genetic architecture of EOC subtypes. To this end, we used data of 10,014 invasive EOC patients and 21,233 controls from the Ovarian Cancer Association Consortium genotyped in the iCOGS array (211,155 SNPs). We estimate the array heritability (attributable to variants tagged on arrays) of each subtype and their genetic correlations. We also look for genetic overlaps with factors such as obesity, smoking behaviors, diabetes, age at menarche and height. We estimated the array heritabilities of high-grade serous disease ([Formula: see text] = 8.8 ± 1.1 %), endometrioid ([Formula: see text] = 3.2 ± 1.6 %), clear cell ([Formula: see text] = 6.7 ± 3.3 %) and all EOC ([Formula: see text] = 5.6 ± 0.6 %). Known associated loci contributed approximately 40 % of the total array heritability for each subtype. The contribution of each chromosome to the total heritability was not proportional to chromosome size. Through bivariate and cross-trait LD score regression, we found evidence of shared genetic backgrounds between the three high-grade subtypes: serous, endometrioid and undifferentiated. Finally, we found significant genetic correlations of all EOC with diabetes and obesity using a polygenic prediction approach. PMID:27075448

  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...... and LUM are not directly associated with sEOC, and that confirmation of possible effect modification of the variants by non-genetic factors is required....

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

    OpenAIRE

    André L. M. Verbeek; Johan Bulten; van Niekerk, Catharina. C.

    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 epithelial ovarian cancer. Methods. A cross-sectional study within a large population-based dataset. Results. Skin cancer was found in 2.7% (95% CI: 2.3–3.1) of the 5366 individuals forming our dataset...

  6. 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

  7. 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

    with epithelial ovarian cancer in a gene-by-gene analysis (P = 0.002) with a positive finding (q value = 0.240). Using a multivariate model search algorithm over 11 IL18 tagging SNPs, we found that the association was best modeled by rs1834481. Further, this SNP uniquely tagged......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...... nucleotide polymorphisms (SNP) in several candidate gene pathways in 848 epithelial ovarian cancer cases and 798 controls in the North Carolina Ovarian Cancer Study (NCO) using a customized Illumina array. The inflammation gene interleukin-18 (IL18) showed the strongest evidence for association...

  8. Tubal ligation and salpingectomy and the risk of epithelial ovarian cancer and borderline ovarian tumors

    DEFF Research Database (Denmark)

    Madsen, C; Baandrup, Louise; Dehlendorff, Christian;

    2015-01-01

    OBJECTIVE: According to the recent theories on the ovarian cancer origin, any protective effect of tubal ligation may vary with histologic subtype of ovarian cancer. Furthermore, bilateral salpingectomy may represent an opportunity for surgical prevention of serous ovarian cancer. DESIGN: Nationw......OBJECTIVE: According to the recent theories on the ovarian cancer origin, any protective effect of tubal ligation may vary with histologic subtype of ovarian cancer. Furthermore, bilateral salpingectomy may represent an opportunity for surgical prevention of serous ovarian cancer. DESIGN...

  9. 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...

  10. 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...

  11. Identification of Epithelial Ovarian Tumor-Specific Aptamers

    OpenAIRE

    Benedetto, Gregory; Hamp, Timothy J; Wesselman, Peter J.; Richardson, Christine

    2015-01-01

    Ovarian cancer is often diagnosed in late stages with few treatment options and poor long-term prognosis. New clinical tools for early detection of ovarian malignancies will significantly help reduce mortality and improve current long-term survival rates. The objective of this work was to identify ovarian tumor-specific single-stranded DNA aptamers that bind to malignant ovarian tumor cells and internalize with high affinity and specificity. Aptamers can identify unique tumor biomarkers, can ...

  12. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Amankwah, Ernest K; Lin, Hui-Yi; Tyrer, Jonathan P; Lawrenson, Kate; Dennis, Joe; Chornokur, Ganna; Aben, Katja K H; Anton-Culver, Hoda; Antonenkova, Natalia; Bruinsma, Fiona; Bandera, Elisa V; Bean, Yukie T; Beckmann, Matthias W; Bisogna, Maria; Bjorge, Line; Bogdanova, Natalia; Brinton, Louise A; Brooks-Wilson, Angela; Bunker, Clareann H; Butzow, Ralf; Campbell, Ian G; Carty, Karen; Chen, Zhihua; Chen, Y Ann; Chang-Claude, Jenny; Cook, Linda S; Cramer, Daniel W; Cunningham, Julie M; Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; du Bois, Andreas; Despierre, Evelyn; Dicks, Ed; Doherty, Jennifer A; Dörk, Thilo; Dürst, Matthias; Easton, Douglas F; Eccles, Diana M; Edwards, Robert P; Ekici, Arif B; Fasching, Peter A; Fridley, Brooke L; Gao, Yu-Tang; Gentry-Maharaj, Aleksandra; Giles, Graham G; Glasspool, Rosalind; Goodman, Marc T; Gronwald, Jacek; Harrington, Patricia; Harter, Philipp; Hasmad, Hanis N; Hein, Alexander; Heitz, Florian; Hildebrandt, Michelle A T; Hillemanns, Peter; Hogdall, Claus K; Hogdall, Estrid; Hosono, Satoyo; Iversen, Edwin S; Jakubowska, Anna; Jensen, Allan; Ji, Bu-Tian; Karlan, Beth Y; Jim, Heather; Kellar, Melissa; Kiemeney, Lambertus A; Krakstad, Camilla; Kjaer, Susanne K; Kupryjanczyk, Jolanta; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D; Lee, Alice W; Lele, Shashi; Leminen, Arto; Lester, Jenny; Levine, Douglas A; Liang, Dong; Lim, Boon Kiong; Lissowska, Jolanta; Lu, Karen; Lubinski, Jan; Lundvall, Lene; Massuger, Leon F A G; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R; McNeish, Ian; Menon, Usha; Milne, Roger L; Modugno, Francesmary; Moysich, Kirsten B; Ness, Roberta B; Nevanlinna, Heli; Eilber, Ursula; Odunsi, Kunle; Olson, Sara H; Orlow, Irene; Orsulic, Sandra; Weber, Rachel Palmieri; Paul, James; Pearce, Celeste L; Pejovic, Tanja; Pelttari, Liisa M; Permuth-Wey, Jennifer; Pike, Malcolm C; Poole, Elizabeth M; Risch, Harvey A; Rosen, Barry; Rossing, Mary Anne; Rothstein, Joseph H; Rudolph, Anja; Runnebaum, Ingo B; Rzepecka, Iwona K; Salvesen, Helga B; Schernhammer, Eva; Schwaab, Ira; Shu, Xiao-Ou; Shvetsov, Yurii B; Siddiqui, Nadeem; Sieh, Weiva; Song, Honglin; Southey, Melissa C; Spiewankiewicz, Beata; Sucheston-Campbell, Lara; Teo, Soo-Hwang; Terry, Kathryn L; Thompson, Pamela J; Thomsen, Lotte; Tangen, Ingvild L; Tworoger, Shelley S; van Altena, Anne M; Vierkant, Robert A; Vergote, Ignace; Walsh, Christine S; Wang-Gohrke, Shan; Wentzensen, Nicolas; Whittemore, Alice S; Wicklund, Kristine G; Wilkens, Lynne R; Wu, Anna H; Wu, Xifeng; Woo, Yin-Ling; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Kelemen, Linda E; Berchuck, Andrew; Schildkraut, Joellen M; Ramus, Susan J; Goode, Ellen L; Monteiro, Alvaro N A; Gayther, Simon A; Narod, Steven A; Pharoah, Paul D P; Sellers, Thomas A; Phelan, Catherine M

    2015-12-01

    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 contribute to epithelial ovarian carcinoma (EOC) risk have been based on small sample sizes and none have sought replication in an independent population. We screened 15,816 single-nucleotide polymorphisms (SNPs) in 296 genes in a discovery phase using data from a genome-wide association study of EOC among women of European ancestry (1,947 cases and 2,009 controls) and identified 793 variants in 278 EMT-related genes that were nominally (P < 0.05) associated with invasive EOC. These SNPs were then genotyped in a larger study of 14,525 invasive-cancer patients and 23,447 controls. A P-value <0.05 and a false discovery rate (FDR) <0.2 were considered statistically significant. In the larger dataset, GPC6/GPC5 rs17702471 was associated with the endometrioid subtype among Caucasians (odds ratio (OR) = 1.16, 95% CI = 1.07-1.25, P = 0.0003, FDR = 0.19), whereas F8 rs7053448 (OR = 1.69, 95% CI = 1.27-2.24, P = 0.0003, FDR = 0.12), F8 rs7058826 (OR = 1.69, 95% CI = 1.27-2.24, P = 0.0003, FDR = 0.12), and CAPN13 rs1983383 (OR = 0.79, 95% CI = 0.69-0.90, P = 0.0005, FDR = 0.12) were associated with combined invasive EOC among Asians. In silico functional analyses revealed that GPC6/GPC5 rs17702471 coincided with DNA regulatory elements. These results suggest that EMT gene variants do not appear to play a significant role in the susceptibility to EOC. PMID:26399219

  15. Rare non-epithelial ovarian neoplasms: Pathology, genetics and treatment.

    Science.gov (United States)

    Foulkes, William D; Gore, Martin; McCluggage, W Glenn

    2016-07-01

    Rare non-epithelial ovarian neoplasms have posed management challenges for many years. Their rarity means that most specialist practitioners will see one such case every several years, and most generalists may never see a case. The first step in management is to establish the correct diagnosis and this may necessitate specialist pathology review. Here, we review recent developments in the pathology, genetics and treatment of small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) and sex cord-stromal tumours. Pathologically, these tumours often display morphological overlap with other neoplasms; for example, SCCOHT overlaps with many other "small round blue cell" tumours. Specific immunohistochemical stains, while useful, may not always be definitive. The discovery of somatic mutations in FOXL2 (adult granulosa cell tumours) and germline and somatic mutations in DICER1 (Sertoli-Leydig cell tumours) and SMARCA4 (SCCOHT) has demonstrated the value of molecular investigation as an adjunct to traditional histopathological approaches. In addition, the presence of germline mutations in a significant proportion of some of these neoplasms points to the need for genetic counselling and testing, offering the prospect of prevention and early diagnosis. Treatment of these rare tumours, as a group, should be on the basis of sound oncological principles, given that level 1 evidence will almost always be lacking. The rationale for experimental therapies must be clearly established. In view of the complex issues involved in the management of these conditions, expert opinion in pathology, genetics and treatment may be essential to offer the patient and her family the best chance of a good outcome. PMID:27079213

  16. 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).

  17. Current status and evolution of preclinical drug development models of epithelial ovarian cancer

    Directory of Open Access Journals (Sweden)

    Panagiotis A Konstantinopoulos

    2013-12-01

    Full Text Available Epithelial ovarian cancer (EOC is the most lethal gynecologic malignancy and the fifth most common cause of female cancer death in the United States. Although important advances in surgical and chemotherapeutic strategies over the last three decades have significantly improved the median survival of EOC patients, the plateau of the survival curve has not changed appreciably. Given that EOC is a genetically and biologically heterogeneous disease, identification of specific molecular abnormalities that can be targeted in each individual ovarian cancer on the basis of predictive biomarkers promises to be an effective strategy to improve outcome in this disease. However, for this promise to materialize, appropriate preclinical experimental platforms that recapitulate the complexity of these neoplasms and reliably predict antitumor activity in the clinic are critically important. In this review, we will present the current status and evolution of preclinical models of EOC, including cell lines, immortalized normal cells, xenograft models, patient-derived xenografts and animal models, and will discuss their potential for oncology drug development.

  18. Next generation sequencing approaches to identify novel susceptibility genes for epithelial ovarian cancer

    OpenAIRE

    Hayward, J. D.

    2014-01-01

    Ovarian cancer is the fifth most common cancer in women in developed countries and is associated with poor survival due to late diagnoses. Strategies focusing on detecting the disease in the earliest stages and/or improving risk prediction may represent effective clinical intervention reducing disease burden. Women at the greatest risk of epithelial ovarian cancer (EOC) can be offered prophylactic risk-reducing salpingo-oopherectomy (RRSO), which is currently only offered to women with mutati...

  19. Metabolomic Characterization of Ovarian Epithelial Carcinomas by HRMAS-NMR Spectroscopy

    Directory of Open Access Journals (Sweden)

    D. Ben Sellem

    2011-01-01

    Full Text Available Objectives. The objectives of the present study are to determine if a metabolomic study by HRMAS-NMR can (i discriminate between different histological types of epithelial ovarian carcinomas and healthy ovarian tissue, (ii generate statistical models capable of classifying borderline tumors and (iii establish a potential relationship with patient's survival or response to chemotherapy. Methods. 36 human epithelial ovarian tumor biopsies and 3 healthy ovarian tissues were studied using 1H HRMAS NMR spectroscopy and multivariate statistical analysis. Results. The results presented in this study demonstrate that the three histological types of epithelial ovarian carcinomas present an effective metabolic pattern difference. Furthermore, a metabolic signature specific of serous (N-acetyl-aspartate and mucinous (N-acetyl-lysine carcinomas was found. The statistical models generated in this study are able to predict borderline tumors characterized by an intermediate metabolic pattern similar to the normal ovarian tissue. Finally and importantly, the statistical model of serous carcinomas provided good predictions of both patient's survival rates and the patient's response to chemotherapy. Conclusions. Despite the small number of samples used in this study, the results indicate that metabolomic analysis of intact tissues by HRMAS-NMR is a promising technique which might be applicable to the therapeutic management of patients.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    2016-08-19

    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

  2. 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 ...

  3. Polymorphisms in NF-κB Inhibitors and Risk of Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Kelemen Linda E

    2009-06-01

    Full Text Available Abstract Background The nuclear factor-κB (NF-κB family is a set of transcription factors with key roles in the induction of the inflammatory response and may be the link between inflammation and cancer development. This pathway has been shown to influence ovarian epithelial tissue repair. Inhibitors of κB (IκB prevent NF-κB activation by sequestering NF-κB proteins in the cytoplasm until IκB proteins are phosphorylated and degraded. Methods We used a case-control study to evaluate the association between single nucleotide polymorphisms (SNPs in NFKBIA and NFKBIB (the genes encoding IκBα and IκBβ, respectively and risk of epithelial ovarian cancer. We queried 19 tagSNPs and putative-functional SNPs among 930 epithelial ovarian cancer cases and 1,037 controls from two studies. Results The minor allele for one synonymous SNP in NFKBIA, rs1957106, was associated with decreased risk (p = 0.03. Conclusion Considering the number of single-SNP tests performed and null gene-level results, we conclude that NFKBIA and NFKBIB are not likely to harbor ovarian cancer risk alleles. Due to its biological significance in ovarian cancer, additional genes encoding NF-κB subunits, activating and inhibiting molecules, and signaling molecules warrant interrogation.

  4. Polymorphisms in NF-κB Inhibitors and Risk of Epithelial Ovarian Cancer

    International Nuclear Information System (INIS)

    The nuclear factor-κB (NF-κB) family is a set of transcription factors with key roles in the induction of the inflammatory response and may be the link between inflammation and cancer development. This pathway has been shown to influence ovarian epithelial tissue repair. Inhibitors of κB (IκB) prevent NF-κB activation by sequestering NF-κB proteins in the cytoplasm until IκB proteins are phosphorylated and degraded. We used a case-control study to evaluate the association between single nucleotide polymorphisms (SNPs) in NFKBIA and NFKBIB (the genes encoding IκBα and IκBβ, respectively) and risk of epithelial ovarian cancer. We queried 19 tagSNPs and putative-functional SNPs among 930 epithelial ovarian cancer cases and 1,037 controls from two studies. The minor allele for one synonymous SNP in NFKBIA, rs1957106, was associated with decreased risk (p = 0.03). Considering the number of single-SNP tests performed and null gene-level results, we conclude that NFKBIA and NFKBIB are not likely to harbor ovarian cancer risk alleles. Due to its biological significance in ovarian cancer, additional genes encoding NF-κB subunits, activating and inhibiting molecules, and signaling molecules warrant interrogation

  5. 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

  6. 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

  7. 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...

  8. 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

  9. 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.

  10. 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

    ; AIFM2, AKTIP, AXIN2, CASP5, FILIP1L, RBBP8, RGC32, RUVBL1 and STAG3. Sixty-three tagging single nucleotide polymorphisms (tSNPs) in these genes were genotyped in 1,799 invasive ovarian cancer cases and 3,045 controls to look for associations with disease risk. Two SNPs in RUVBL1, rs13063604 and rs...... and 6,031 controls from ten sites from the United States, Europe and Australia; however, neither SNP was significant in Stage 2. We also evaluated the potential role of tSNPs in these nine genes in ovarian cancer development by testing for allele-specific loss of heterozygosity (LOH) in 286 primary......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...

  11. Dihydroartiminisin inhibits the growth and metastasis of epithelial ovarian cancer.

    Science.gov (United States)

    Wu, Buchu; Hu, Ke; Li, Shu; Zhu, Jing; Gu, Liying; Shen, Haoran; Hambly, Brett D; Bao, Shisan; Di, Wen

    2012-01-01

    Dihydroartiminisin (DHA), the active component of a Chinese herb (Artemisia annua), has been utilised as an anti-malarial drug since ancient China. DHA has also been shown to inhibit proliferation of cancer in vitro. However, the capacity of DHA to inhibit the development of ovarian cancer is still unclear. The adhesion, invasion, and migration of human ovarian cancer cell line (HO8910PM) was determined following DHA treatment in vitro, using Matrigel coated plate, transwell membrane chamber, and wound healing models, respectively. A mouse ovarian cancer model was established by orthotopic inoculation of HO8910PM cell line in nude mice. The growth and metastasis in vivo was determined 8 weeks post-implantation in response to DHA treatment. The expression of phosphorylated focal adhesion kinase (pFAK) and matrix metalloproteinases (MMP-2 and MMP-9) was evaluated using Western blotting. The expression of Von Willebrand factor (vWF) and infiltration of macrophages were determined, using immunohistochemistry. DHA inhibits ovarian cancer cell proliferation, adhesion, migration and invasion in vitro in a dose-dependent manner, consistent with decreased expression of pFAK and MMP-2, but not MMP-9. DHA inhibited metastasis significantly in vivo, associated with reduced vWF expression and macrophage infiltration. In conclusion, DHA inhibits the development of ovarian cancer, in part via down-regulating pFAK, MMP-2, vWF and macrophage infiltration. PMID:22025319

  12. 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

  13. 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

    BACKGROUND: Epidemiological studies that have investigated the association between coffee, tea and caffeine consumption and ovarian cancer risk have produced conflicting results. Furthermore, only few studies have examined the role of coffee and tea consumption separately for borderline ovarian...... 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....... RESULTS: Both coffee (OR = 0.90; 95% CI 0.84-0.97 per cup/day) and total caffeine consumption from coffee and tea combined (OR = 0.93; 95% CI 0.88-0.98 per 100 mg/day) decreased the risk of ovarian cancer. These associations were significant only for the serous and "other" subtypes of ovarian cancer...

  14. 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.

  15. 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.

  16. 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.

  17. 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...

  18. 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.

  19. 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...... 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...

  20. Avian prostatic acid phosphatase: estrogen regulation in the oviduct and epithelial cell-derived ovarian carcinomas.

    Science.gov (United States)

    Bae, Hyocheol; Lim, Whasun; Bae, Seung-Min; Bazer, Fuller W; Choi, Youngsok; Song, Gwonhwa

    2014-07-01

    Prostatic acid phosphatase (ACPP) is a glycoprotein that is mainly synthesized and secreted by glandular epithelial cells (GE) of the prostate, and it is well known as a biomarker for prostate cancer. Although ACPP was used as prognostic/diagnostic indicator and studied to elucidate regulatory mechanism(s) during several decades in humans, its role is not clearly understood. Gene profiling data using a chicken DNA microarray revealed that ACPP increased significantly during remodeling and recrudescence of the oviduct in response to estrogen. Thus, in this study, we investigated the expression and hormonal regulation of ACPP gene in the reproductive tracts of chickens. ACPP was specifically detected in the luminal cells (LE) and GE of chicken oviduct, and diethylstilbestrol (a synthetic nonsteroidal estrogen) stimulated its expression during development of the oviduct. In addition, ACPP mRNA and protein were localized to LE and GE during the regeneration phase of the oviduct of laying hens during induced molting. Furthermore, ACPP mRNA and protein were abundant in GE of ovarian carcinoma, but not in normal ovaries. Moreover, strong expression of ACPP protein was detected in epithelial cells of cancerous ovaries from women. Collectively, results of the present study are the first to show that ACPP is a novel estrogen-stimulated gene in the oviductal epithelial cells of the chicken and that its expression increases significantly in epithelial cells of ovarian carcinoma, which indicates that it may be a candidate biomarker for diagnosis of epithelia-derived ovarian cancer in women. PMID:24829029

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

    Science.gov (United States)

    Jim, Heather S.L.; Lin, Hui-Yi; Tyrer, Jonathan P.; Lawrenson, Kate; Dennis, Joe; Chornokur, Ganna; Chen, Zhihua; Chen, Ann Y.; Permuth-Wey, Jennifer; Aben, Katja KH.; Anton-Culver, Hoda; Antonenkova, Natalia; Bruinsma, Fiona; Bandera, Elisa V.; Bean, Yukie T.; Beckmann, Matthias W.; Bisogna, Maria; Bjorge, Line; Bogdanova, Natalia; Brinton, Louise A.; Brooks-Wilson, Angela; Bunker, Clareann H.; Butzow, Ralf; Campbell, Ian G.; Carty, Karen; Chang-Claude, Jenny; Cook, Linda S.; Cramer, Daniel W.; Cunningham, Julie M.; Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; du Bois, Andreas; Despierre, Evelyn; Sieh, Weiva; Doherty, Jennifer A.; Dörk, Thilo; Dürst, Matthias; Easton, Douglas F.; Eccles, Diana M.; Edwards, Robert P.; Ekici, Arif B.; Fasching, Peter A.; Fridley, Brooke L.; Gao, Yu-Tang; Gentry-Maharaj, Aleksandra; Giles, Graham G.; Glasspool, Rosalind; Goodman, Marc T.; Gronwald, Jacek; Harter, Philipp; Hasmad, Hanis N.; Hein, Alexander; Heitz, Florian; Hildebrandt, Michelle A.T.; Hillemanns, Peter; Hogdall, Claus K.; Hogdall, Estrid; Hosono, Satoyo; Iversen, Edwin S.; Jakubowska, Anna; Jensen, Allan; Ji, Bu-Tian; Karlan, Beth Y.; Kellar, Melissa; Kiemeney, Lambertus A.; Krakstad, Camilla; Kjaer, Susanne K.; Kupryjanczyk, Jolanta; Vierkant, Robert A.; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D.; Lee, Alice W.; Lele, Shashi; Leminen, Arto; Lester, Jenny; Levine, Douglas A.; Liang, Dong; Lim, Boon Kiong; Lissowska, Jolanta; Lu, Karen; Lubinski, Jan; Lundvall, Lene; Massuger, Leon F.A.G.; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R.; McNeish, Ian; Menon, Usha; Milne, Roger L.; Modugno, Francesmary; Thomsen, Lotte; Moysich, Kirsten B.; Ness, Roberta B.; Nevanlinna, Heli; Eilber, Ursula; Odunsi, Kunle; Olson, Sara H.; Orlow, Irene; Orsulic, Sandra; Palmieri Weber, Rachel; Paul, James; Pearce, Celeste L.; Pejovic, Tanja; Pelttari, Liisa M.; Pike, Malcolm C.; Poole, Elizabeth M.; Schernhammer, Eva; Risch, Harvey A.; Rosen, Barry; Rossing, Mary Anne; Rothstein, Joseph H.; Rudolph, Anja; Runnebaum, Ingo B.; Rzepecka, Iwona K.; Salvesen, Helga B.; Schwaab, Ira; Shu, Xiao-Ou; Shvetsov, Yurii B.; Siddiqui, Nadeem; Song, Honglin; Southey, Melissa C.; Spiewankiewicz, Beata; Sucheston-Campbell, Lara; Teo, Soo-Hwang; Terry, Kathryn L.; Thompson, Pamela J.; Tangen, Ingvild L.; Tworoger, Shelley S.; van Altena, Anne M.; Vergote, Ignace; Walsh, Christine S.; Wang-Gohrke, Shan; Wentzensen, Nicolas; Whittemore, Alice S.; Wicklund, Kristine G.; Wilkens, Lynne R.; Wu, Anna H.; Wu, Xifeng; Woo, Yin-Ling; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Amankwah, Ernest; Berchuck, Andrew; Schildkraut, Joellen M.; Kelemen, Linda E.; Ramus, Susan J.; Monteiro, Alvaro N.A.; Goode, Ellen L.; Narod, Steven A.; Gayther, Simon A.; Pharoah, Paul D. P.; Sellers, Thomas A.; Phelan, Catherine M.

    2016-01-01

    Disruption in circadian gene expression, whether due to genetic variation or environmental factors (e.g., light at night, shiftwork), is associated with increased incidence of breast, prostate, gastrointestinal and hematologic cancers and gliomas. Circadian genes are highly expressed in the ovaries where they regulate ovulation; circadian disruption is associated with several ovarian cancer risk factors (e.g., endometriosis). However, no studies have examined variation in germline circadian genes as predictors of ovarian cancer risk and invasiveness. The goal of the current study was to examine single nucleotide polymorphisms (SNPs) in circadian genes BMAL1, CRY2, CSNK1E, NPAS2, PER3, REV1 and TIMELESS and downstream transcription factors KLF10 and SENP3 as predictors of risk of epithelial ovarian cancer (EOC) and histopathologic subtypes. The study included a test set of 3,761 EOC cases and 2,722 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 association was rs117104877 in BMAL1 (OR = 0.79, 95% CI = 0.68–0.90, p = 5.59 × 10−4]. Functional analysis revealed a significant down regulation of BMAL1 expression following cMYC overexpression and increasing transformation in ovarian surface epithelial (OSE) cells as well as alternative splicing of BMAL1 exons in ovarian and granulosa cells. These results suggest that variation in circadian genes, and specifically BMAL1, may be associated with risk of ovarian cancer, likely through disruption of hormonal pathways. PMID:26807442

  2. Genomic aberrations relate early and advanced stage ovarian cancer

    NARCIS (Netherlands)

    A. Zaal; W.J. Peyrot (Wouter ); P.M.J.J. Berns (Els); M.E.L. van der Burg (Maria); J.H.W. Veerbeek (Jan ); J.B. Trimbos; I. Cadron (Isabelle); P.J. van Diest (Paul); W.N. Wieringen (Wessel); O. Krijgsman (Oscar); G.A. Meijer (Gerrit); J.M.J. Piek (Jurgen ); P.J. Timmers (Petra); I. Vergote (Ignace); R.H.M. Verheijen (René); B. Ylstra (Bauke); R.P. Zweemer (Ronald )

    2012-01-01

    textabstractBackground Because of the distinct clinical presentation of early and advanced stage ovarian cancer, we aim to clarify whether these disease entities are solely separated by time of diagnosis or whether they arise from distinct molecular events. Methods Sixteen early and sixteen advanced

  3. Survival Advantage Associated with Decrease in Stage at Detection from Stage IIIC to Stage IIIA Epithelial Ovarian Cancer

    OpenAIRE

    John Hoff; Lauren Baldwin; Jason Lefringhouse; Edward Pavlik; Rachel Miller; Christopher DeSimone; Frederick Ueland; Thomas Tucker; Richard Kryscio; van Nagell, J. R.

    2014-01-01

    Objective. The aim of this study was to document the survival advantage of lowering stage at detection from Stage IIIC to Stage IIIA epithelial ovarian cancer. Methods. Treatment outcomes and survival were evaluated in patients with Stage IIIA and Stage IIIC epithelial ovarian cancer treated from 2000 to 2009 at the University of Kentucky Markey Cancer Center (UKMCC) and SEER institutions. Results. Cytoreduction to no visible disease (P < 0.0001) and complete response to platinum-based chemot...

  4. A phase II study of combination chemotherapy in early relapsed epithelial ovarian cancer using gemcitabine and pegylated liposomal doxorubicin

    DEFF Research Database (Denmark)

    Mirza, Mansoor Raza; Lund, Bente; Lindegaard, Jacob Christian;

    2010-01-01

    Treatment of epithelial ovarian cancer patients relapsing with a short treatment-free interval (TFI) after prior chemotherapy is unsatisfactory. This phase II trial evaluated the activity and feasibility of pegylated liposomal doxorubicin (PLD) plus gemcitabine in this setting.......Treatment of epithelial ovarian cancer patients relapsing with a short treatment-free interval (TFI) after prior chemotherapy is unsatisfactory. This phase II trial evaluated the activity and feasibility of pegylated liposomal doxorubicin (PLD) plus gemcitabine in this setting....

  5. Genetic Risk Assessment for Women with Epithelial Ovarian Cancer: Referral Patterns and Outcomes in a University Gynecologic Oncology Clinic

    OpenAIRE

    Petzel, Sue v.; Vogel, Rachel Isaksson; Bensend, Tracy; Leininger, Anna; Argenta, Peter A.; Geller, Melissa A.

    2013-01-01

    Little is known about genetic service utilization and ovarian cancer. We identified the frequency and outcome of genetic counseling referral, predictors of referral, and referral uptake for ovarian cancer patients. Using pathology reports, we identified all epithelial ovarian cancer patients seen in a university gynecologic oncology clinic (1/04–8/06). Electronic medical records (EMR) were used to document genetic service referral, time from diagnosis-to-referral, point-in-treatment at referr...

  6. 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.

  7. Intraperitoneal gene therapy by rAAV provides long-term survival against epithelial ovarian cancer independently of survivin pathway.

    Science.gov (United States)

    Isayeva, T; Ren, C; Ponnazhagan, S

    2007-01-01

    Epithelial ovarian carcinoma is the leading cause of death from gynecological malignancies. Owing to the lack of an effective screening method, insidious onset, and non-specific symptoms, a majority of women present with advanced stage disease. Despite improvements from cytoreductive surgery and chemotherapy, recurrent disease remains a formidable challenge. In the present study, we demonstrate for the first time that stable intra-abdominal genetic transfer of endostatin and angiostatin (E+A) by recombinant adeno-associated virus (rAAV) provides sustained antitumor effects on the growth and dissemination of epithelial ovarian cancer in a mouse model. Further, when combined with paclitaxel (taxol), the effect of this therapy was dramatically increased and resulted in long-term tumor-free survival overcoming prior limitations of chemotherapy and gene therapy. The combined effects of angiosuppressive therapy and chemotherapy were found to be independently of survivin pathway. Evidence for the superior effects of the combination therapy was indicated by significantly lower ascites volume with less hemorrhage and tumor conglomerates, lower ascites vascular endothelial growth factor, higher tumor cell apoptosis and decreased blood vasculature, and long-term disease-free survival. Histopathology of visceral organs and liver enzyme assays indicated no toxicity or pathology. PMID:16943851

  8. 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.

  9. 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.

  10. Intake of specific carotenoids and the risk of epithelial ovarian cancer.

    Science.gov (United States)

    Zhang, Min; Holman, C D'Arcy J; Binns, Colin W

    2007-07-01

    There has been considerable interest in the role of carotenoids in the chemoprevention of cancer. However, few studies have examined the association between intake of specific carotenoids and the risk of epithelial ovarian cancer and the results for carotenoids have been inconclusive. To investigate whether the intake of alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein and zeaxanthin, and lycopene is inversely associated with ovarian cancer risk, a case-control study was conducted in China during 1999-2000. The cases were 254 patients with histologically confirmed epithelial ovarian cancer and 652 age-matched controls were randomly recruited during the same period. Habitual dietary intake and lifestyle were collected by face-to-face interview using a validated and reliable FFQ. The US Department of Agriculture nutrient composition database was used to calculate the intake of specific carotenoids. Unconditional logistic regression analyses were used to estimate OR and 95 % CI, accounting for age, locality, education, BMI, smoking, tea drinking, parity, oral contraceptive use, hormone replacement therapy, menopausal status, family history of ovarian cancer, physical activity and energy intake. Compared with the highest v. the lowest quartile of intake, the adjusted OR were 0.39 (95 % CI 0.23, 0.66) for alpha-carotene, 0.51 (95 % CI 0.31, 0.84) for beta-carotene, 0.51 (95 % CI 0.31, 0.83) for beta-cryptoxanthin, 0.45 (0.27, 0.76) for lutein and zeaxanthin, and 0.33 (95 % CI 0.20, 0.56) for total carotenoids, with statistically significant tests for trend. It is concluded that a higher intake of carotenoids can reduce the risk of epithelial ovarian cancer. PMID:17367574

  11. Regulatory T lymphocytes and transforming growth factor beta in epithelial ovarian tumors-prognostic significance

    OpenAIRE

    Winkler, Izabela; Wilczynska, Barbara; Bojarska-Junak, Agnieszka; Gogacz, Marek; Adamiak, Aneta; Postawski, Krzysztof; Darmochwal-Kolarz, Dorota; Rechberger, Tomasz; Tabarkiewicz, Jacek

    2015-01-01

    Background Regulatory T lymphocytes (Treg) are characterized by the presence of CD4+ surface antigen. Today the transcription factor FOXP3 is considered to be the most specific marker of Treg cells. The aim of the study was to estimate the percentage of Treg in peripheral blood and the tissue of the epithelial ovarian tumor and blood serum TGF-beta concentrations and relationships between them. Moreover, the aim of the study was to answer the question whether the percentage of Treg lymphocyte...

  12. Molecular Pathogenesis and Extraovarian Origin of Epithelial Ovarian Cancer. Shifting the Paradigm

    OpenAIRE

    Kurman, Robert J; Shih, Ie-Ming

    2011-01-01

    Recent morphologic, immunohistochemical and molecular genetic studies have led to the development of a new paradigm for the pathogenesis and origin of epithelial ovarian cancer (EOC) based on a dualistic model of carcinogenesis that divides EOC into two broad categories designated type I and type II. Type I tumors are comprised of low-grade serous, low-grade endometrioid, clear cell and mucinous carcinomas and Brenner tumors. They are generally indolent, present in stage I (tumor confined to ...

  13. 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...

  14. [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.

  15. 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.

  16. Targeting the ROR1 and ROR2 receptors in epithelial ovarian cancer inhibits cell migration and invasion

    Science.gov (United States)

    Henry, Claire; Llamosas, Estelle; Knipprath-Mészáros, Alexandra; Schoetzau, Andreas; Obermann, Ellen; Fuenfschilling, Maya; Caduff, Rosemarie; Fink, Daniel; Hacker, Neville; Ward, Robyn; Heinzelmann-Schwarz, Viola; Ford, Caroline

    2015-01-01

    AIM In recent years, the Wnt signalling pathway has been implicated in epithelial ovarian cancer and its members have potential as diagnostic, prognostic and therapeutic targets. Here we investigated the role of two Wnt receptor tyrosine kinases (RTKs), ROR1 and ROR2, and their putative ligand, Wnt5a, in ovarian cancer. METHODS Immunohistochemistry for ROR2 was performed in a large patient cohort, including benign controls, borderline tumours and epithelial ovarian cancer. In addition, siRNA was used to silence ROR1, ROR2 and Wnt5a individually, and together, in two ovarian cancer cell lines, and the effects on cell proliferation, adhesion, migration and invasion were measured. RESULTS ROR2 expression is significantly increased in ovarian cancer patients compared to patients with benign disease. In vitro assays showed that silencing either receptor inhibits ovarian cancer cell migration and invasion, and concurrently silencing both receptors has an even stronger inhibitory effect on proliferation, migration and invasion. CONCLUSIONS ROR2 expression is increased in epithelial ovarian cancer, and silencing ROR2 and its sister receptor ROR1 has a strong inhibitory effect on the ability of ovarian cancer cells to proliferate, migrate and invade through an extracellular matrix. PMID:26515598

  17. 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...

  18. Paclitaxel, Polyglutamate Paclitaxel, or Observation in Treating Patients With Stage III or Stage IV Ovarian Epithelial, Peritoneal Cancer, or Fallopian Tube Cancer

    Science.gov (United States)

    2016-03-17

    Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Malignant Ovarian Mixed Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Primary Peritoneal Serous Adenocarcinoma; 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 Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

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

    Directory of Open Access Journals (Sweden)

    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.

  20. 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 ch...

  1. 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...

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

    Directory of Open Access Journals (Sweden)

    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.

  3. 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.

  4. Neoadjuvant chemotherapy versus primary surgery in advanced ovarian carcinoma

    OpenAIRE

    Elshamy Maged R; Setit Ahmed E; Elshafei Mohamed A; Hegazi Refaat AF; Hegazy Mohamed AF; Eltatoongy Mohamed; Halim Amal AF

    2005-01-01

    Abstract Background Patients with advanced ovarian cancer should be treated by radical debulking surgery aiming at complete tumor resection. Unfortunately about 70% of the patients present with advanced disease, when optimal debulking can not be obtained, and therefore these patients gain little benefit from surgery. Neoadjuvant chemotherapy (NACT) has been proposed as a novel therapeutic approach in such cases. In this study, we report our results with primary surgery or neoadjuvant chemothe...

  5. Immunohistochemical profiling of benign, low malignant potential and low grade serous epithelial ovarian tumors

    International Nuclear Information System (INIS)

    Serous epithelial ovarian tumors can be subdivided into benign (BOV), low malignant potential (LMP) or borderline and invasive (TOV) tumors. Although the molecular characteristics of serous BOV, LMP and low grade (LG) TOV tumors has been initiated, definitive immunohistochemical markers to distinguish between these tumor types have not been defined. In the present study, we used a tissue array composed of 27 BOVs, 78 LMPs and 23 LG TOVs to evaluate the protein expression of a subset of selected candidates identified in our previous studies (Ape1, Set, Ran, Ccne1 and Trail) or known to be implicated in epithelial ovarian cancer disease (p21, Ccnb1, Ckd1). Statistically significant difference in protein expression was observed for Ccnb1 when BOV tumors were compared to LMP tumors (p = 0.003). When BOV were compared to LG TOV tumors, Trail was significantly expressed at a higher level in malignant tumors (p = 0.01). Expression of p21 was significantly lower in LG tumors when compared with either BOVs (p = 0.03) or LMPs (p = 0.001). We also observed that expression of p21 was higher in LMP tumors with no (p = 0.02) or non-invasive (p = 0.01) implants compared to the LMP associated with invasive implants. This study represents an extensive analyse of the benign and highly differentiated ovarian disease from an immunohistochemical perspective

  6. Immunohistochemical profiling of benign, low malignant potential and low grade serous epithelial ovarian tumors

    Directory of Open Access Journals (Sweden)

    Rancourt Claudine

    2008-11-01

    Full Text Available Abstract Background Serous epithelial ovarian tumors can be subdivided into benign (BOV, low malignant potential (LMP or borderline and invasive (TOV tumors. Although the molecular characteristics of serous BOV, LMP and low grade (LG TOV tumors has been initiated, definitive immunohistochemical markers to distinguish between these tumor types have not been defined. Methods In the present study, we used a tissue array composed of 27 BOVs, 78 LMPs and 23 LG TOVs to evaluate the protein expression of a subset of selected candidates identified in our previous studies (Ape1, Set, Ran, Ccne1 and Trail or known to be implicated in epithelial ovarian cancer disease (p21, Ccnb1, Ckd1. Results Statistically significant difference in protein expression was observed for Ccnb1 when BOV tumors were compared to LMP tumors (p = 0.003. When BOV were compared to LG TOV tumors, Trail was significantly expressed at a higher level in malignant tumors (p = 0.01. Expression of p21 was significantly lower in LG tumors when compared with either BOVs (p = 0.03 or LMPs (p = 0.001. We also observed that expression of p21 was higher in LMP tumors with no (p = 0.02 or non-invasive (p = 0.01 implants compared to the LMP associated with invasive implants. Conclusion This study represents an extensive analyse of the benign and highly differentiated ovarian disease from an immunohistochemical perspective.

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

    International Nuclear Information System (INIS)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  11. Pegylated liposomal doxorubicin: appraisal of its current role in the management of epithelial ovarian cancer

    Directory of Open Access Journals (Sweden)

    Markman M

    2011-06-01

    Full Text Available Maurie MarkmanCancer Treatment Centers of America, Eastern Regional Medical Center, Philadelphia, PA, USAAbstract: Pegylated liposomal doxorubicin (PLD has become a major component in the routine management of epithelial ovarian cancer. The drug is frequently employed as a single agent in the platinum-resistant setting, and recently reported data reveal the superiority of the combination of PLD plus carboplatin, compared with the platinum drug plus paclitaxel, in delaying the time to disease progression in women with recurrent (potentially platinum-sensitive disease. Current research efforts involving PLD in ovarian cancer are focusing on adding novel targeted drugs to this cytotoxic agent. The utility of such approaches in the platinum-resistant population, compared with the sequential administration of single agents active in this setting, remains to be determined.Keywords: PLD, carboplatin, paclitaxel, platinum-sensitive, platinum-resistant

  12. The clinical implications of new insights into the origins of epithelial ovarian cancer with emphasis on the British Columbia Ovarian Cancer Prevention Initiative

    Directory of Open Access Journals (Sweden)

    Dianne Miller

    2016-01-01

    Full Text Available In the last ten years our understanding of the origin of epithelial ovarian cancer has changed. This includes the realization that the majority of High Grade serous cancers originate in fallopian tube epithelium and the majority of endometroid and clear cell cancer arise in foci of endometriosis. These new insights have profound implications of both prevention and treatment.

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

    Directory of Open Access Journals (Sweden)

    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

  14. 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.

  15. Genetic polymorphisms in the Paraoxonase 1 gene and risk of ovarian epithelial carcinoma.

    Science.gov (United States)

    Lurie, Galina; Wilkens, Lynne R; Thompson, Pamela J; McDuffie, Katharine E; Carney, Michael E; Terada, Keith Y; Goodman, Marc T

    2008-08-01

    Oxidative stress during successive ovulations increases the opportunity for DNA damage to ovarian epithelial cells and the potential for malignant transformation. Paraoxonase 1 (PON1) is an endogenous free radical scavenger that reduces oxidative stress. The association of two common functional single nucleotide polymorphisms (SNP), rs854560 T>A and rs662 A>G, with the risk of epithelial ovarian cancer was examined in a population-based case-control study in Hawaii. A personal interview and blood specimens were collected from 274 women with histologically confirmed, primary ovarian cancer and 452 controls frequency matched on age and ethnicity. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated by unconditional logistic regression. Both PON1 SNPs were significantly associated with ovarian cancer risk. The ORs were 0.53 (95% CI, 0.35-0.79; P for allele-dose effect = 0.01) for women carrying the rs854560 T allele compared with women with the AA genotype and 0.65 (95% CI, 0.44-0.95; P for allele-dose effect = 0.03) for women carrying the rs662 A allele compared with women with the GG genotype. The association of the rs854560 T genotype with risk was stronger among smokers (OR, 0.33; 95% CI, 0.17-0.64; P for allele-dose effect = 0.0007) than among nonsmokers (OR, 0.68; 95% CI, 0.40-1.18; P for allele-dose effect = 0.53). The decreased risk associated with the rs854560 T allele was also stronger among obese women (OR, 0.19; 95% CI, 0.06-0.55; P for allele-dose effect = 0.007) than among nonobese women (OR, 0.62; 95% CI, 0.40-0.98; P for allele-dose effect = 0.16). Our study provides evidence for an association of two PON1 SNPs with the risk of epithelial ovarian cancer. Possible effect modification of these associations by tobacco smoking and obesity needs confirmation in other studies. PMID:18708400

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

    DEFF Research Database (Denmark)

    Hjortkjær, Mette; Waldstrøm, Marianne; Jakobsen, Anders;

    2016-01-01

    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 and...

  17. Polymorphisms in NF-κB Inhibitors and Risk of Epithelial Ovarian Cancer

    OpenAIRE

    Kelemen Linda E; Cunningham Julie M; Schildkraut Joellen M; Knutson Keith L; Anderson Stephanie; Fridley Brooke L; Phelan Catherine M; Vierkant Robert A; White Kristin L; Pankratz V Shane; Rider David N; Liebow Mark; Hartmann Lynn C; Sellers Thomas A; Goode Ellen L

    2009-01-01

    Abstract Background The nuclear factor-κB (NF-κB) family is a set of transcription factors with key roles in the induction of the inflammatory response and may be the link between inflammation and cancer development. This pathway has been shown to influence ovarian epithelial tissue repair. Inhibitors of κB (IκB) prevent NF-κB activation by sequestering NF-κB proteins in the cytoplasm until IκB proteins are phosphorylated and degraded. Methods We used a case-control study to evaluate the asso...

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

    OpenAIRE

    Paddock Lisa E; Chandran Urmila; King Melony; Bandera Elisa V; Rodriguez-Rodriguez Lorna; Olson Sara H

    2011-01-01

    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 (C...

  19. Ovarian cancer at young age: the contribution of mismatch-repair defects in a population-based series of epithelial ovarian

    DEFF Research Database (Denmark)

    Domanska, K; Malander, S; Måsbäck, A;

    2007-01-01

    At least one of ten patients with ovarian cancer is estimated to develop their tumor because of heredity with the breast and ovarian cancer syndrome due to mutations in the BRCA1 and BRCA2 genes and hereditary nonpolyposis colorectal cancer (HNPCC) being the major genetic causes. Cancer at young...... and endometrioid cancers were overrepresented and were diagnosed in 27% and 16% of the tumors, respectively. Immunostaining using antibodies against MLH1, PMS2, MSH2, and MSH6 was used to assess the mismatch-repair status and revealed loss of expression of MLH1/PMS2 in two cases, loss of MSH2/MSH6 in one case...... age is a hallmark of heredity, and ovarian cancers associated with HNPCC have been demonstrated to develop at a particularly early age. We used the Swedish Cancer Registry to identify a population-based series of 98 invasive epithelial ovarian cancers that developed before 40 years. Mucinous...

  20. 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.

  1. 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

  2. Assessment of the argyrophilic nucleolar organizer region area/nucleus ratio in ovarian serous epithelial adenomas, borderline tumors and cancers

    OpenAIRE

    Gottwald, Leszek; Danilewicz, Marian; Suzin, Jacek; Wagrowska-Danilewicz, Malgorzata; Spych, Michal; Tylinski, Wieslaw; Topczewska-Tylinska, Katarzyna; Piekarski, Janusz; Kazmierczak-Lukaszewicz, Sylwia; Cialkowska-Rysz, Aleksandra

    2013-01-01

    Introduction There is a need to assess the value of the novel potentially useful biomarkers in ovarian tumors. The aim of study was to assess the value of sAgNOR analysis in ovarian serous epithelial tumors. Material and methods The analysis was performed in ovaries from 113 patients treated operatively due to serous ovarian tumors (30 adenomas, 14 borderline tumors and 69 cancers). After silver staining of paraffin specimens from surgery, sAgNOR in tumor cells was analyzed. Additionally, the...

  3. 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

  4. 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

  5. 节律化疗作为体力状况较差的晚期卵巢上皮癌患者的姑息治疗%Metronomic chemotherapy as a palliative treatment in poor performance status patients with advanced epithelial ovarian carcinoma

    Institute of Scientific and Technical Information of China (English)

    Eman I.Ismail; Mohamed A.Elgawad

    2011-01-01

    Objective: The aim of our study was to evaluate the clinical efficacy and tolerability of metronomic chemotherapy in patients with advanced ovarian carcinoma. Methods: Fifteen patients with advanced ovarian carcinoma and bad performance status were subjected to daily cyclophosphamide(CTX)after failure of 1st line chemotherapy which included paditaxel and carboplatin. Evaluation of the cases during treatment as regard treatment side effects and progression free survival. Results: Patients could tolerate low dose oral cyclophosphamide treatment without considerable side effects with improvement of performance status. The mean progression free survival was 12 months. Conclusion: Low dose oral cydophosphamide could be considered as a palliative treatment of pretreated ovarian carcinomas with poor performance status.

  6. 新辅助化疗联合间隔减瘤术在晚期卵巢癌中的临床应用研究%Clinical application research of neoadjuvant chemotherapy followed by interval debulking surgery in advanced epithelial ovarian cancer patients

    Institute of Scientific and Technical Information of China (English)

    李菁; 沈立翡; 朱岚; 蔡蕾

    2015-01-01

    Objective To explore the application value of neoadjuvant chemotherapy followed by interval debulking surgery ( NAC/IDS) in treating patients with advanced epithelial ovarian cancer ( EOC) . Methods We retrospectively reviewed 109 patients with stage IIIC or IV EOC treated at Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from June 2000 to January 2013. 53 patients underwent PDS were selected into PDS group, while 56 patients underwent NAC/IDS were selected into NAC/IDS group, the survival rate and perioperative morbidity were compared between two groups. Results No difference in overall survival (OS) or progression-free survival (PFS) were observed between NAC/IDS group and PDS group (P>0. 05). The optimal debulking rate of NAC/IDS group (53. 6 %) was significantly higher than that of the PDS group (43. 4 %) (P0.05)。 NACT/IDS组手术切除率(53.6%)明显高于PDS组(43.4%)(P<0.05);NACT/IDS组手术出血量、术后恢复、并发症的发生情况优于PDS组(P<0.05)。结论 NACT/IDS增加了手术切除率,减少了手术创伤,术后生存率与PDS无明显差异。在Ⅲc期和Ⅳ期卵巢癌患者,并非强调直接行PDS,NACT/IDS是有效的治疗方法。

  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. 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

  9. 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.

  10. 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

  11. Overexpression of piRNA pathway genes in epithelial ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Shu Ly Lim

    Full Text Available The importance of the Piwi-interacting RNA (piRNA pathway for germ cell maintenance, genome integrity, DNA methylation and retrotransposon control raises possible roles of this pathway in cancer. Indeed aberrant expression of human PIWI orthologs and Maelstrom has been observed in various cancers. In this study we explored the expression and function of piRNA pathway genes in human ovarian cancer, based on our recent work, which showed widespread expression of piRNA pathway genes in the mammalian. Our work shows that PIWIL1 and MAEL expression is significantly increased in malignant EOC (n = 25 compared to benign tumor tissues (n = 19 and normal ovarian tissue (n = 8. The expression of PIWIL3 is lower in malignant and benign tissues when compared to normal ovary. Sequencing of PIWIL1 transcript revealed that in many tumors deletion of exon 17 leads to the introduction of a premature stop codon in the PIWI domain, likely due to a splicing error. In situ hybridization on tumor sections revealed that L1, PIWIL1, 2 and MAEL are specifically expressed in epithelial cells (cancerous cells of EOC. Furthermore, PIWIL2 and MAEL are co-expressed in the stromal cells adjacent to tumor cells. Since PIWIL1 and MAEL are up regulated in malignant EOC and expressed in the epithelial cells, we investigated if these two genes affect invasiveness of ovarian cancer cell lines that do not normally express these genes. PIWIL1 and MAEL were transiently over expressed in the ovarian cancer cell line SKOV3, followed by real-time measurements of cell invasiveness. Surprisingly both PIWIL1 and MAEL over expression decreased the invasiveness of SKOV3 cells. Our findings support a growing body of evidence that shows that genes in this pathway are upregulated in cancer. In ovarian cancer we show for the first time that Piwil1 transcript may often be abnormal result in non functional product. In contrast to what has been observed in other cell types, we found that PIWIL1 and

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. 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

  17. Can advanced-stage ovarian cancer be cured?

    Science.gov (United States)

    Narod, Steven

    2016-04-01

    Approximately 20% of women with advanced-stage ovarian cancer survive beyond 12 years after treatment and are effectively cured. Initial therapy for ovarian cancer comprises surgery and chemotherapy, and is given with the goal of eradicating as many cancer cells as possible. Indeed, the three phases of therapy are as follows: debulking surgery to remove as much of the cancer as possible, preferably to a state of no visible residual disease; chemotherapy to eradicate any microscopic disease that remains present after surgery; and second-line or maintenance therapy, which is given to delay disease progression among patients with tumour recurrence. If no cancer cells remain after initial therapy is completed, a cure is expected. By contrast, if residual cancer cells are present after initial treatment, then disease recurrence is likely. Thus, the probability of cure is contingent on the combination of surgery and chemotherapy effectively eliminating all cancer cells. In this Perspectives article, I present the case that the probability of achieving a cancer-free state is maximized through a combination of maximal debulking surgery and intraperitoneal chemotherapy. I discuss the evidence indicating that by taking this approach, cures could be achieved in up to 50% of women with advanced-stage ovarian cancer. PMID:26787282

  18. 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.

  19. 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

  20. 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....

  1. 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...

  2. Clinical use of cancer biomarkers in epithelial ovarian cancer: updated guidelines from the European Group on Tumor Markers

    NARCIS (Netherlands)

    Sölétormos, G.; Duffy, M.J.; Othman Abu Hassan, S.; Verheijen, RHM; Tholander, B.; Bast jr., R.C.; Gaarenstroom, K.N.; Sturgeon, C.M.; Bonfrer, J.M.G.; Petersen, P.H.; Troonen, H.; Carlo Torre, G.; Kanty Kulpa, J.; Tuxen, M.K.; Molina, R.

    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 sens

  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. Epithelial-Mesenchymal Transition (EMT) gene variants and Epithelial Ovarian Cancer (EOC) risk

    Science.gov (United States)

    Amankwah, Ernest K.; Lin, Hui-Yi; Tyrer, Jonathan P.; Lawrenson, Kate; Dennis, Joe; Chornokur, Ganna; Aben, Katja KH.; Anton-Culver, Hoda; Antonenkova, Natalia; Bruinsma, Fiona; Bandera, Elisa V.; Bean, Yukie T.; Beckmann, Matthias W.; Bisogna, Maria; Bjorge, Line; Bogdanova, Natalia; Brinton, Louise A.; Brooks-Wilson, Angela; Bunker, Clareann H.; Butzow, Ralf; Campbell, Ian G.; Carty, Karen; Chen, Zhihua; Chen, Y. Ann; Chang-Claude, Jenny; Cook, Linda S.; Cramer, Daniel W.; Cunningham, Julie M.; Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; du Bois, Andreas; Despierre, Evelyn; Dicks, Ed; Doherty, Jennifer A.; Dörk, Thilo; Dürst, Matthias; Easton, Douglas F.; Eccles, Diana M.; Edwards, Robert P.; Ekici, Arif B.; Fasching, Peter A.; Fridley, Brooke L.; Gao, Yu-Tang; Gentry-Maharaj, Aleksandra; Giles, Graham G.; Glasspool, Rosalind; Goodman, Marc T.; Gronwald, Jacek; Harrington, Patricia; Harter, Philipp; Hasmad, Hanis N.; Hein, Alexander; Heitz, Florian; Hildebrandt, Michelle A.T.; Hillemanns, Peter; Hogdall, Claus K.; Hogdall, Estrid; Hosono, Satoyo; Iversen, Edwin S.; Jakubowska, Anna; Jensen, Allan; Ji, Bu-Tian; Karlan, Beth Y.; Jim, Heather; Kellar, Melissa; Kiemeney, Lambertus A.; Krakstad, Camilla; Kjaer, Susanne K.; Kupryjanczyk, Jolanta; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D.; Lee, Alice W.; Lele, Shashi; Leminen, Arto; Lester, Jenny; Levine, Douglas A.; Liang, Dong; Lim, Boon Kiong; Lissowska, Jolanta; Lu, Karen; Lubinski, Jan; Lundvall, Lene; Massuger, Leon F.A.G.; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R.; McNeish, Ian; Menon, Usha; Milne, Roger L.; Modugno, Francesmary; Moysich, Kirsten B.; Ness, Roberta B.; Nevanlinna, Heli; Eilber, Ursula; Odunsi, Kunle; Olson, Sara H.; Orlow, Irene; Orsulic, Sandra; Weber, Rachel Palmieri; Paul, James; Pearce, Celeste L.; Pejovic, Tanja; Pelttari, Liisa M.; Permuth-Wey, Jennifer; Pike, Malcolm C.; Poole, Elizabeth M.; Risch, Harvey A.; Rosen, Barry; Rossing, Mary Anne; Rothstein, Joseph H.; Rudolph, Anja; Runnebaum, Ingo B.; Rzepecka, Iwona K.; Salvesen, Helga B.; Schernhammer, Eva; Schwaab, Ira; Shu, Xiao-Ou; Shvetsov, Yurii B.; Siddiqui, Nadeem; Sieh, Weiva; Song, Honglin; Southey, Melissa C.; Spiewankiewicz, Beata; Sucheston-Campbell, Lara; Teo, Soo-Hwang; Terry, Kathryn L.; Thompson, Pamela J.; Thomsen, Lotte; Tangen, Ingvild L.; Tworoger, Shelley S.; van Altena, Anne M.; Vierkant, Robert A.; Vergote, Ignace; Walsh, Christine S.; Wang-Gohrke, Shan; Wentzensen, Nicolas; Whittemore, Alice S.; Wicklund, Kristine G.; Wilkens, Lynne R.; Wu, Anna H.; Wu, Xifeng; Woo, Yin-Ling; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Kelemen, Linda E.; Berchuck, Andrew; Schildkraut, Joellen M.; Ramus, Susan J.; Goode, Ellen L.; Monteiro, Alvaro N.A.; Gayther, Simon A.; Narod, Steven A.; Pharoah, Paul D. P.; Sellers, Thomas A.; Phelan, Catherine M.

    2016-01-01

    Introduction 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 contribute to EOC risk have been based on small sample sizes and none have sought replication in an independent population. Methods We screened 1254 SNPs in 296 genes in a discovery phase using data from a genome-wide association study of EOC among women of European ancestry (1,947 cases and 2,009 controls) and identified 793 variants in 278 EMT-related genes that were nominally (p<0.05) associated with invasive EOC. These SNPs were then genotyped in a larger study of 14,525 invasive-cancer patients and 23,447 controls. A p-value <0.05 and a false discovery rate (FDR) <0.2 was considered statistically significant. Results In the larger dataset, GPC6/GPC5 rs17702471 was associated with the endometrioid subtype among Caucasians (OR=1.16, 95%CI=1.07–1.25, p=0.0003, FDR=0.19), while F8 rs7053448 (OR=1.69, 95%CI=1.27–2.24, p=0.0003, FDR=0.12), F8 rs7058826 (OR=1.69, 95%CI=1.27–2.24, p=0.0003, FDR=0.12), and CAPN13 rs1983383 (OR=0.79, 95%CI=0.69–0.90, p=0.0005, FDR=0.12) were associated with combined invasive EOC among Asians. In silico functional analyses revealed that GPC6/GPC5 rs17702471 coincided with DNA regulatory elements. Conclusion These results suggest that EMT gene variants do not appear to play a significant role in the susceptibility to EOC. PMID:26399219

  5. 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.

  6. 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

    -based chemotherapy. Other data suggest Tau protein expression as a predictor of clinical outcome in cancer patients treated with paclitaxel-based chemotherapy as low tau expression may render microtubules more vulnerable to paclitaxel. Therefore, the combination of ERCC1 and Tau may be a valuable predictor...... 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...... patients were used for immunohistochemical staining for ERCC1 and Tau proteins. All patients received standard first-line combination platinum and paclitaxel chemotherapy. The patients were divided in a training set of 84 patients and an independent validation cohort of 143 patients. Neither ERCC1 nor Tau...

  7. Cancer stem cells from epithelial ovarian cancer patients privilege oxidative phosphorylation, and resist glucose deprivation.

    Science.gov (United States)

    Pastò, Anna; Bellio, Chiara; Pilotto, Giorgia; Ciminale, Vincenzo; Silic-Benussi, Micol; Guzzo, Giulia; Rasola, Andrea; Frasson, Chiara; Nardo, Giorgia; Zulato, Elisabetta; Nicoletto, Maria Ornella; Manicone, Mariangela; Indraccolo, Stefano; Amadori, Alberto

    2014-06-30

    We investigated the metabolic profile of cancer stem cells (CSC) isolated from patients with epithelial ovarian cancer. CSC overexpressed genes associated with glucose uptake, oxidative phosphorylation (OXPHOS), and fatty acid β-oxidation, indicating higher ability to direct pyruvate towards the Krebs cycle. Consistent with a metabolic profile dominated by OXPHOS, the CSC showed higher mitochondrial reactive oxygen species (ROS) production and elevated membrane potential, and underwent apoptosis upon inhibition of the mitochondrial respiratory chain. The CSC also had a high rate of pentose phosphate pathway (PPP) activity, which is not typical of cells privileging OXPHOS over glycolysis, and may rather reflect the PPP role in recharging scavenging enzymes. Furthermore, CSC resisted in vitro and in vivo glucose deprivation, while maintaining their CSC phenotype and OXPHOS profile. These observations may explain the CSC resistance to anti-angiogenic therapies, and indicate this peculiar metabolic profile as a possible target of novel treatment strategies. PMID:24946808

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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. PMID:25581431

  13. Survival Advantage Associated with Decrease in Stage at Detection from Stage IIIC to Stage IIIA Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    John Hoff

    2014-01-01

    Full Text Available Objective. The aim of this study was to document the survival advantage of lowering stage at detection from Stage IIIC to Stage IIIA epithelial ovarian cancer. Methods. Treatment outcomes and survival were evaluated in patients with Stage IIIA and Stage IIIC epithelial ovarian cancer treated from 2000 to 2009 at the University of Kentucky Markey Cancer Center (UKMCC and SEER institutions. Results. Cytoreduction to no visible disease (P<0.0001 and complete response to platinum-based chemotherapy (P<0.025 occurred more frequently in Stage IIIA than in Stage IIIC cases. Time to progression was shorter in patients with Stage IIIC ovarian cancer (17±1 months than in those with Stage II1A disease (36±8 months. Five-year overall survival (OS improved from 41% in Stage IIIC patients to 60% in Stage IIIA patients treated at UKMCC and from 37% to 56% in patients treated at SEER institutions for a survival advantage of 19% in both data sets. 53% of Stage IIIA and 14% of Stage IIIC patients had NED at last followup. Conclusions. Decreasing stage at detection from Stage IIIC to stage IIIA epithelial ovarian cancer is associated with a 5-year survival advantage of nearly 20% in patients treated by surgical tumor cytoreduction and platinum-based chemotherapy.

  14. 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. PMID:27075926

  15. Prognostic Value of Residual Disease after Interval Debulking Surgery for FIGO Stage IIIC and IV Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Marianne J. Rutten

    2015-01-01

    Full Text Available Although complete debulking surgery for epithelial ovarian cancer (EOC is more often achieved with interval debulking surgery (IDS following neoadjuvant chemotherapy (NACT, randomized evidence shows no long-term survival benefit compared to complete primary debulking surgery (PDS. We performed an observational cohort study of patients treated with debulking surgery for advanced EOC to evaluate the prognostic value of residual disease after debulking surgery. All patients treated between 1998 and 2010 in three Dutch referral gynaecological oncology centres were included. The prognostic value of residual disease after surgery for disease specific survival was assessed using Cox-regression analyses. In total, 462 patients underwent NACT-IDS and 227 PDS. Macroscopic residual disease after debulking surgery was an independent prognostic factor for survival in both treatment modalities. Yet, residual tumour less than one centimetre at IDS was associated with a survival benefit of five months compared to leaving residual tumour more than one centimetre, whereas this benefit was not seen after PDS. Leaving residual tumour at IDS is a poor prognostic sign as it is after PDS. The specific prognostic value of residual tumour seems to depend on the clinical setting, as minimal instead of gross residual tumour is associated with improved survival after IDS, but not after PDS.

  16. 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.

  17. Germline BRCA1/2 mutation testing is indicated in every patient with epithelial ovarian cancer: A systematic review.

    Science.gov (United States)

    Arts-de Jong, Marieke; de Bock, Geertruida H; van Asperen, Christi J; Mourits, Marian J E; de Hullu, Joanne A; Kets, C Marleen

    2016-07-01

    The presence of a germline BRCA1/2 mutation improves options for tailored risk-reducing strategies and treatment in both breast and ovarian cancer patients and their relatives. Currently, referral for germline BRCA1/2 mutation testing of women with epithelial ovarian cancer (EOC) varies widely, based on different criteria, such as age of onset, family history of breast and/or ovarian cancer and histological type of EOC. The overall probability of a germline BRCA1/2 mutation in women with EOC is above 10%, and a substantial part of the germline BRCA1/2 mutation carriers is missed when applying these criteria for referral. Therefore, we strongly recommend referral of all women with EOC for genetic counselling and DNA analysis. PMID:27209246

  18. Specific glycosylation of membrane proteins in epithelial ovarian cancer cell lines: glycan structures reflect gene expression and DNA methylation status.

    Science.gov (United States)

    Anugraham, Merrina; Jacob, Francis; Nixdorf, Sheri; Everest-Dass, Arun Vijay; Heinzelmann-Schwarz, Viola; Packer, Nicolle H

    2014-09-01

    Epithelial ovarian cancer is the fifth most common cause of cancer in women worldwide bearing the highest mortality rate among all gynecological cancers. Cell membrane glycans mediate various cellular processes such as cell signaling and become altered during carcinogenesis. The extent to which glycosylation changes are influenced by aberrant regulation of gene expression is nearly unknown for ovarian cancer and remains crucial in understanding the development and progression of this disease. To address this effect, we analyzed the membrane glycosylation of non-cancerous ovarian surface epithelial (HOSE 6.3 and HOSE 17.1) and serous ovarian cancer cell lines (SKOV 3, IGROV1, A2780, and OVCAR 3), the most common histotype among epithelial ovarian cancers. N-glycans were released from membrane glycoproteins by PNGase F and analyzed using nano-liquid chromatography on porous graphitized carbon and negative-ion electrospray ionization mass spectrometry (ESI-MS). Glycan structures were characterized based on their molecular masses and tandem MS fragmentation patterns. We identified characteristic glycan features that were unique to the ovarian cancer membrane proteins, namely the "bisecting N-acetyl-glucosamine" type N-glycans, increased levels of α 2-6 sialylated N-glycans and "N,N'-diacetyl-lactosamine" type N-glycans. These N-glycan changes were verified by examining gene transcript levels of the enzymes specific for their synthesis (MGAT3, ST6GAL1, and B4GALNT3) using qRT-PCR. We further evaluated the potential epigenetic influence on MGAT3 expression by treating the cell lines with 5-azacytidine, a DNA methylation inhibitor. For the first time, we provide evidence that MGAT3 expression may be epigenetically regulated by DNA hypomethylation, leading to the synthesis of the unique "bisecting GlcNAc" type N-glycans on the membrane proteins of ovarian cancer cells. Linking the observation of specific N-glycan substructures and their complex association with epigenetic

  19. Variation in NF-κB signaling pathways and survival in invasive epithelial ovarian cancer.

    Science.gov (United States)

    Block, Matthew S; Charbonneau, Bridget; Vierkant, Robert A; Fogarty, Zachary; Bamlet, William R; Pharoah, Paul D P; Rossing, Mary Anne; Cramer, Daniel; Pearce, Celeste Leigh; Schildkraut, Joellen; Menon, Usha; Kjaer, Susanne K; Levine, Douglas A; Gronwald, Jacek; Culver, Hoda Anton; Whittemore, Alice S; Karlan, Beth Y; Lambrechts, Diether; Wentzensen, Nicolas; Kupryjanczyk, Jolanta; Chang-Claude, Jenny; Bandera, Elisa V; Hogdall, Estrid; Heitz, Florian; Kaye, Stanley B; Fasching, Peter A; Campbell, Ian; Goodman, Marc T; Pejovic, Tanja; Bean, Yukie T; Hays, Laura E; Lurie, Galina; Eccles, Diana; Hein, Alexander; Beckmann, Matthias W; Ekici, Arif B; Paul, James; Brown, Robert; Flanagan, James M; Harter, Philipp; du Bois, Andreas; Schwaab, Ira; Hogdall, Claus K; Lundvall, Lene; Olson, Sara H; Orlow, Irene; Paddock, Lisa E; Rudolph, Anja; Eilber, Ursula; Dansonka-Mieszkowska, Agnieszka; Rzepecka, Iwona K; Ziolkowska-Seta, Izabela; Brinton, Louise A; Yang, Hannah; Garcia-Closas, Montserrat; Despierre, Evelyn; Lambrechts, Sandrina; Vergote, Ignace; Walsh, Christine S; Lester, Jenny; Sieh, Weiva; McGuire, Valerie; Rothstein, Joseph H; Ziogas, Argyrios; Lubiński, Jan; Cybulski, Cezary; Menkiszak, Janusz; Jensen, Allan; Gayther, Simon A; Ramus, Susan J; Gentry-Maharaj, Aleksandra; Berchuck, Andrew; Wu, Anna H; Pike, Malcolm C; Van Den Berg, David; Terry, Kathryn L; Vitonis, Allison F; Ramirez, Starr M; Rider, David N; Knutson, Keith L; Sellers, Thomas A; Phelan, Catherine M; Doherty, Jennifer A; Johnatty, Sharon E; deFazio, Anna; Song, Honglin; Tyrer, Jonathan; Kalli, Kimberly R; Fridley, Brooke L; Cunningham, Julie M; Goode, Ellen L

    2014-07-01

    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 inflammatory responses, including the response to cancer. We studied common inherited variation in 210 genes in the NF-κB family in 10,084 patients with invasive EOC (5,248 high-grade serous, 1,452 endometrioid, 795 clear cell, and 661 mucinous) from the Ovarian Cancer Association Consortium. Associations between genotype and overall survival were assessed using Cox regression for all patients and by major histology, adjusting for known prognostic factors and correcting for multiple testing (threshold for statistical significance, P < 2.5 × 10(-5)). Results were statistically significant when assessed for patients of a single histology. Key associations were with caspase recruitment domain family, member 11 (CARD11) rs41324349 in patients with mucinous EOC [HR, 1.82; 95% confidence interval (CI), 1.41-2.35; P = 4.13 × 10(-6)] and tumor necrosis factor receptor superfamily, member 13B (TNFRSF13B) rs7501462 in patients with endometrioid EOC (HR, 0.68; 95% CI, 0.56-0.82; P = 2.33 × 10(-5)). Other associations of note included TNF receptor-associated factor 2 (TRAF2) rs17250239 in patients with high-grade serous EOC (HR, 0.84; 95% CI, 0.77-0.92; P = 6.49 × 10(-5)) and phospholipase C, gamma 1 (PLCG1) rs11696662 in patients with clear cell EOC (HR, 0.43; 95% CI, 0.26-0.73; P = 4.56 × 10(-4)). These associations highlight the potential importance of genes associated with host inflammation and immunity in modulating clinical outcomes in distinct EOC histologies. PMID:24740199

  20. Development of a Mouse Model of Menopausal Ovarian Cancer

    OpenAIRE

    Elizabeth R Smith; Ying eWang; Xiang-Xi Mike Xu

    2014-01-01

    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 progressi...

  1. 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.

  2. Late results of chemotherapy of the advanced ovarian cancer

    International Nuclear Information System (INIS)

    Out of 108 patients with advanced ovarian cancer treated by postoperative combined chemotherapy with cisplatin, 13% survived 5 years, 11% with NED and 1.8% with signs of the disease. 67.6% patients responded to treatment in 33.3% of them it was CR and in 34.3% - PR. There was a close relationship between the type of response and survival, as 2 years survived 63.8% patients with CR, 31.4% with PR and only 5.4% of non-responders. Ten out of 36 patients with CR survived 5 years with NED, but out of 4 patients with PR 2 patients survived without symptoms and 2 with signs of the disease. During further follow-up in 4 out of 12 patients who survived 5 years with NED progression of cancer was diagnosed. (author)

  3. Analysis of the gene expression profile in response to human epididymis protein 4 in epithelial ovarian cancer cells.

    Science.gov (United States)

    Zhu, Liancheng; Guo, Qian; Jin, Shan; Feng, Huilin; Zhuang, Huiyu; Liu, Cong; Tan, Mingzi; Liu, Juanjuan; Li, Xiao; Lin, Bei

    2016-09-01

    Currently, there are emerging multiple studies on human epididymis protein 4 (HE4) in ovarian cancer. HE4 possesses higher sensitivity and specificity than CA125 in the confirmative early diagnosis for ovarian cancer. Although much attention has been given to explore its clinical application, research of the basic mechanisms of HE4 in ovarian cancer are still unclear. In the present study, we provide fundamental data to identify full-scale differentially expressed genes (DEGs) in response to HE4 by use of human whole-genome microarrays in human epithelial ovarian cancer cell line ES-2 following overexpression and silencing of HE4. We found that a total of 717 genes were upregulated and 898 genes were downregulated in the HE4-overexpressing cells vs. the HE4-Mock cells, and 166 genes were upregulated and 285 were downregulated in the HE4-silenced cells vs. the HE4-Mock cells. An overlap of 16 genes consistently upregulated and 8 genes downregulated in response to HE4 were noted. These DEGs were involved in MAPK, steroid biosynthesis, cell cycle, the p53 hypoxia pathway, and focal adhesion pathways. Interaction network analysis predicted that the genes participated in the regulatory connection. Highly differential expression of the FOXA2, SERPIND1, BDKRD1 and IL1A genes was verified by quantitative real-time PCR in 4 cell line samples. Finally, SERPIND1 (HCII) was validated at the protein level by immunohistochemistry in 107 paraffin-embedded ovarian tissues. We found that SERPIND1 may act as a potential oncogene in the development of ovarian cancer. The present study displayed the most fundamental and full-scale data to show DEGs in response to HE4. These identified genes may provide a theoretical basis for investigations of the underlying molecular mechanism of HE4 in ovarian cancer. PMID:27430660

  4. 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

    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...... 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...

  5. 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.

  6. 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...... that is in LD (r(2 )=( )0.90) with a previously identified 'best hit' (rs7651446) mapping to an intron of TIPARP. Suggestive associations (5.0 × 10 (-)  (5 )>( )P≥5.0 ×10 (-)  (7)) were detected for rare and low-frequency variants at 16 novel loci. Four rare missense variants were identified (ACTBL2 rs73757391.......67 × 10 (-)  (4); PSKAT-o = 1.07 × 10 (-)  (5)), reaffirming variant-level analysis. In summary, this large study identified several rare and low-frequency variants and genes that may contribute to EOC susceptibility, albeit with possible small effects. Future studies that integrate epidemiology...

  7. Tolerance and place of irradiation in the treatment of ovarian epithelial cancers

    International Nuclear Information System (INIS)

    In a retrospective analysis, our aim was to evaluate the immediate tolerance and the early and late complications of abdomino-pelvic radiotherapy in the Centre Alexis-Vautrin (France) In this retrospective analysis of 117 epithelial ovarian cancers, treated over 10 years and which all received pelvic and/or abdominal irradiation, we can conclude that this treatment is globally well tolerated and that it yields a low morbidity rate. However, present indications should be considered as an alternative to chemotherapy for stage Ic and stage II tumors except for serous stage II tumors. Lastly, for stage III tumors or for undifferentiated tumors, in the absence of macroscopic residuum, and after platinum containing chemotherapy, abdominal irradiation can be an alternative to systemic or intraperitoneal consolidation chemotherapy. This is supported by three arguments, its short duration, its good tolerance and low toxicity, as well as its low cost-efficiency ratio. We propose an abdominal irradiation delivering 20 to 25 Gy in 3 weeks (maximum 15 Gy on kidneys). (authors)

  8. 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...

  9. An RNA interference lethality screen of the human druggable genome to identify molecular vulnerabilities in epithelial ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Geetika Sethi

    Full Text Available Targeted therapies have been used to combat many tumor types; however, few have effectively improved the overall survival in women with epithelial ovarian cancer, begging for a better understanding of this deadly disease and identification of essential drivers of tumorigenesis that can be targeted effectively. Therefore, we used a loss-of-function screening approach to help identify molecular vulnerabilities that may represent key points of therapeutic intervention. We employed an unbiased high-throughput lethality screen using a 24,088 siRNA library targeting over 6,000 druggable genes and studied their effects on growth and/or survival of epithelial ovarian cancer (EOC cell lines. The top 300 "hits" affecting the viability of A1847 cells were rescreened across additional EOC cell lines and non-tumorigenic, human immortalized ovarian epithelial cell lines. Fifty-three gene candidates were found to exhibit effects in all tumorigenic cell lines tested. Extensive validation of these hits refined the list to four high quality candidates (HSPA5, NDC80, NUF2, and PTN. Mechanistic studies show that silencing of three genes leads to increased apoptosis, while HSPA5 silencing appears to alter cell growth through G1 cell cycle arrest. Furthermore, two independent gene expression studies show that NDC80, NUF2 and PTN were significantly aberrantly overexpressed in serous adenocarcinomas. Overall, our functional genomics results integrated with the genomics data provide an important unbiased avenue towards the identification of prospective therapeutic targets for drug discovery, which is an urgent and unmet clinical need for ovarian cancer.

  10. [Hormonal therapy of advanced or relapsed ovarian granulosa cell tumor].

    Science.gov (United States)

    Sun, H; Bai, P

    2016-07-01

    Ovarian granulosa cell tumor is a rare gynecologic malignancy with hormonal activity. Surgical excision is the standard treatment for this disease. Most patients present excellent short term prognosis, however, late relapse often occurs, even after many years. Viable treatments of advanced or relapsed granulosa cell tumor are still limited, and the optimal therapy method has not been established. Compared with chemotherapy and radiotherapy, hormonal therapy is a well-tolerated treatment which can be administrated over a long period of time without serious side effects, and the combined application of hormones may achieve a better outcome. Therefore, hormonal therapy has been suggested as a potential treatment option for patients with advanced or relapsed granulosa cell tumor, and to extend the tumor-free interval and attenuate the disease progression. Future researches should be focused on the identification of the hormonal therapy which may provide the greatest clinical benefit, comparing and analyzing the effects of different combined therapeutic regimens of hormone drugs, and on the synthesis of drugs highly activating estrogen receptor β expressed in the granulosa cell tumor cells. PMID:27531259

  11. Does risk for ovarian malignancy algorithm excel human epididymis protein 4 and ca125 in predicting epithelial ovarian cancer: A meta-analysis

    International Nuclear Information System (INIS)

    Risk for Ovarian Malignancy Algorithm (ROMA) and Human epididymis protein 4 (HE4) appear to be promising predictors for epithelial ovarian cancer (EOC), however, conflicting results exist in the diagnostic performance comparison among ROMA, HE4 and CA125. Remote databases (MEDLINE/PUBMED, EMBASE, Web of Science, Google Scholar, the Cochrane Library and ClinicalTrials.gov) and full texts bibliography were searched for relevant abstracts. All studies included were closely assessed with the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies-2). EOC predictive value of ROMA was systematically evaluated, and comparison among the predictive performances of ROMA, HE4 and CA125 were conducted within the same population. Sensitivity, specificity, DOR (diagnostic odds ratio), LR ± (positive and negative likelihood ratio) and AUC (area under receiver operating characteristic-curve) were summarized with a bivariate model. Subgroup analysis and sensitivity analysis were used to explore the heterogeneity. Data of 7792 tests were retrieved from 11 studies. The overall estimates of ROMA for EOC predicting were: sensitivity (0.89, 95% CI 0.84-0.93), specificity (0.83, 95% CI 0.77-0.88), and AUC (0.93, 95% CI 0.90-0.95). Comparison of EOC predictive value between HE4 and CA125 found, specificity: HE4 (0.93, 95% CI 0.87-0.96) > CA125 (0.84, 95% CI 0.76-0.90); AUC: CA125 (0.88, 95% CI 0.85-0.91) > HE4 (0.82, 95% CI 0.78-0.85). Comparison of OC predictive value between HE4 and CA125 found, AUC: CA125 (0.89, 95% CI 0.85-0.91) > HE4 (0.79, 95% CI 0.76-0.83). Comparison among the three tests for EOC prediction found, sensitivity: ROMA (0.86, 95%CI 0.81-0.91) > HE4 (0.80, 95% CI 0.73-0.85); specificity: HE4 (0.94, 95% CI 0.90-0.96) > ROMA (0.84, 95% CI 0.79-0.88) > CA125 (0.78, 95%CI 0.73-0.83). ROMA is helpful for distinguishing epithelial ovarian cancer from benign pelvic mass. HE4 is not better than CA125 either for EOC or OC prediction. ROMA is promising predictors of

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

    Science.gov (United States)

    Chornokur, Ganna; Lin, Hui-Yi; Tyrer, Jonathan P.; Lawrenson, Kate; Dennis, Joe; Amankwah, Ernest K.; Qu, Xiaotao; Tsai, Ya-Yu; Jim, Heather S. L.; Chen, Zhihua; Chen, Ann Y.; Permuth-Wey, Jennifer; Aben, Katja KH.; Anton-Culver, Hoda; Antonenkova, Natalia; Bruinsma, Fiona; Bandera, Elisa V.; Bean, Yukie T.; Beckmann, Matthias W.; Bisogna, Maria; Bjorge, Line; Bogdanova, Natalia; Brinton, Louise A.; Brooks-Wilson, Angela; Bunker, Clareann H.; Butzow, Ralf; Campbell, Ian G.; Carty, Karen; Chang-Claude, Jenny; Cook, Linda S.; Cramer, Daniel W.; Cunningham, Julie M.; Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; du Bois, Andreas; Despierre, Evelyn; Dicks, Ed; Doherty, Jennifer A.; Dörk, Thilo; Dürst, Matthias; Easton, Douglas F.; Eccles, Diana M.; Edwards, Robert P.; Ekici, Arif B.; Fasching, Peter A.; Fridley, Brooke L.; Gao, Yu-Tang; Gentry-Maharaj, Aleksandra; Giles, Graham G.; Glasspool, Rosalind; Goodman, Marc T.; Gronwald, Jacek; Harrington, Patricia; Harter, Philipp; Hein, Alexander; Heitz, Florian; Hildebrandt, Michelle A. T.; Hillemanns, Peter; Hogdall, Claus K.; Hogdall, Estrid; Hosono, Satoyo; Jakubowska, Anna; Jensen, Allan; Ji, Bu-Tian; Karlan, Beth Y.; Kelemen, Linda E.; Kellar, Mellissa; Kiemeney, Lambertus A.; Krakstad, Camilla; Kjaer, Susanne K.; Kupryjanczyk, Jolanta; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D.; Lee, Alice W.; Lele, Shashi; Leminen, Arto; Lester, Jenny; Levine, Douglas A.; Liang, Dong; Lim, Boon Kiong; Lissowska, Jolanta; Lu, Karen; Lubinski, Jan; Lundvall, Lene; Massuger, Leon F. A. G.; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R.; McNeish, Iain; Menon, Usha; Milne, Roger L.; Modugno, Francesmary; Moysich, Kirsten B.; Ness, Roberta B.; Nevanlinna, Heli; Eilber, Ursula; Odunsi, Kunle; Olson, Sara H.; Orlow, Irene; Orsulic, Sandra; Weber, Rachel Palmieri; Paul, James; Pearce, Celeste L.; Pejovic, Tanja; Pelttari, Liisa M.; Pike, Malcolm C.; Poole, Elizabeth M.; Risch, Harvey A.; Rosen, Barry; Rossing, Mary Anne; Rothstein, Joseph H.; Rudolph, Anja; Runnebaum, Ingo B.; Rzepecka, Iwona K.; Salvesen, Helga B.; Schernhammer, Eva; Schwaab, Ira; Shu, Xiao-Ou; Shvetsov, Yurii B.; Siddiqui, Nadeem; Sieh, Weiva; Song, Honglin; Southey, Melissa C.; Spiewankiewicz, Beata; Sucheston, Lara; Teo, Soo-Hwang; Terry, Kathryn L.; Thompson, Pamela J.; Thomsen, Lotte; Tangen, Ingvild L.; Tworoger, Shelley S.; van Altena, Anne M.; Vierkant, Robert A.; Vergote, Ignace; Walsh, Christine S.; Wang-Gohrke, Shan; Wentzensen, Nicolas; Whittemore, Alice S.; Wicklund, Kristine G.; Wilkens, Lynne R.; Wu, Anna H.; Wu, Xifeng; Woo, Yin-Ling; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Hasmad, Hanis N.; Berchuck, Andrew; Iversen, Edwin S.; Schildkraut, Joellen M.; Ramus, Susan J.; Goode, Ellen L.; Monteiro, Alvaro N. A.; Gayther, Simon A.; Narod, Steven A.; Pharoah, Paul D. P.; Sellers, Thomas A.; Phelan, Catherine M.

    2015-01-01

    Background 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. Methods 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. Results 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). Conclusion These results, generated on a large cohort of women, revealed associations

  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. 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

  16. 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.

  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. Association between common germline genetic variation in 94 candidate genes or regions and risks of invasive epithelial ovarian cancer

    DEFF Research Database (Denmark)

    Quaye, Lydia; Tyrer, Jonathan; Ramus, Susan J;

    2009-01-01

    BACKGROUND: Recent studies have identified several single nucleotide polymorphisms (SNPs) in the population that are associated with variations in the risks of many different diseases including cancers such as breast, prostate and colorectal. For ovarian cancer, the known highly penetrant....... To date, we have genotyped 340 SNPs from 94 candidate genes or regions, in up to 1,491 invasive epithelial ovarian cancer cases and 3,145 unaffected controls from three different population based studies from the UK, Denmark and USA. RESULTS: After adjusting for population stratification by genomic...... control, 18 SNPs (5.3%) were significant at the 5% level, and 5 SNPs (1.5%) were significant at the 1% level. The most significant association was for the SNP rs2107425, located on chromosome 11p15.5, which has previously been identified as a susceptibility allele for breast cancer from a genome wide...

  19. 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.

  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. Three-dimensional culture sensitizes epithelial ovarian cancer cells to EZH2 methyltransferase inhibition

    Science.gov (United States)

    Amatangelo, Michael D.; Garipov, Azat; Li, Hua; Conejo-Garcia, Jose R.; Speicher, David W.; Zhang, Rugang

    2013-01-01

    Inhibitors of EZH2 methyltransferase activity have been demonstrated to selectively suppress the growth of diffused large B cell lymphoma (DLBCL) cells with gain-of-function mutations in EZH2, while exhibiting very limited effects on the growth of DLBCL cells with wild-type EZH2. Given that EZH2 is often overexpressed but not mutated in solid tumors, it is important to investigate the determinants of sensitivity of solid tumor cells to EZH2 inhibitors. In the current study, we show that three-dimensional (3D) culture of epithelial ovarian cancer (EOC) cells that overexpress EZH2 sensitizes these cells to EZH2 methyltransferase inhibition. Treatment of EOC cells with GSK343, a specific inhibitor of EZH2 methyltransferase, decreases the level of H3K27Me3, the product of EZH2’s enzymatic activity. However, GSK343 exhibited limited effects on the growth of EOC cells in conventional two-dimensional (2D) culture. In contrast, GSK343 significantly suppressed the growth of EOC cells cultured in 3D matrigel extracellular matrix (ECM), which more closely mimics the tumor microenvironment in vivo. Notably, GSK343 induces apoptosis of EOC cells in 3D but not 2D culture. In addition, GSK343 significantly inhibited the invasion of EOC cells. In summary, we show that the 3D ECM sensitizes EOC cells to EZH2 methyltransferase inhibition, which suppresses cell growth, induces apoptosis and inhibits invasion. Our findings imply that in EZH2 wild-type solid tumors, the ECM tumor microenvironment plays an important role in determining sensitivity to EZH2 inhibition and suggest that targeting the ECM represents a novel strategy for enhancing EZH2 inhibitor efficacy. PMID:23759589

  2. Sam68 is Overexpressed in Epithelial Ovarian Cancer and Promotes Tumor Cell Proliferation.

    Science.gov (United States)

    Dong, Lijuan; Che, Hailuo; Li, Mingmei; Li, Xuepeng

    2016-01-01

    BACKGROUND Epithelial ovarian cancer (EOC) is the deadliest gynecological malignancy, and evidence is accumulating on how molecular markers may be associated with the origin and process of EOC. Sam68 (Src-associated in mitosis, of 68 kD), is a K homology domain RNA-binding protein that has been investigated as a risk factor in multiple types of tumors. The aim of the present study was to investigate the contribution of the Sam68 gene in the pathogenesis of EOC. MATERIAL AND METHODS Western blot assay and real-time quantitative PCR methods were performed to examine Sam68 expression in EOC tissue specimens. The association of Sam68 expression with clinic-pathologic variables of EOC was evaluated. Then gain-of-function and loss-of-function strategies were adopted to examine the regulation of Sam68 on the proliferation of EOC OVCAR-3 cells using CCK-8 and colony forming assays. RESULTS Sam68 was overexpressed in both mRNA and protein levels in EOC tumor tissue (n=152) in an association with malignant factors of EOC such as International Federation of Gynecology and Obstetrics (FIGO) stage, residual tumor size (cm), histological grade, and lymph node metastasis. In vitro results demonstrated that Sam68 overexpression was upregulated while Sam68 knockdown downregulated the proliferation of EOC OVCAR-3 cells via regulation of cell growth and colony formation. CONCLUSIONS Sam68 was overexpressed in EOC tissue in association with such cancer malignant factors of FIGO stage, histological grade, and lymph node metastasis, and also positively regulated the proliferation of EOC cells. Our research suggests that Sam68 might accelerate cell cycle progression, and present as a prognostic marker for EOC. PMID:27623016

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

    Science.gov (United States)

    Lawrenson, Kate; Iversen, Edwin S; Tyrer, Jonathan; Weber, Rachel Palmieri; Concannon, Patrick; Hazelett, Dennis J; Li, Qiyuan; Marks, Jeffrey R; Berchuck, Andrew; Lee, Janet M; Aben, Katja K H; Anton-Culver, Hoda; Antonenkova, Natalia; Bandera, Elisa V; Bean, Yukie; Beckmann, Matthias W; Bisogna, Maria; Bjorge, Line; Bogdanova, Natalia; Brinton, Louise A; Brooks-Wilson, Angela; Bruinsma, Fiona; Butzow, Ralf; Campbell, Ian G; Carty, Karen; Chang-Claude, Jenny; Chenevix-Trench, Georgia; Chen, Ann; Chen, Zhihua; Cook, Linda S; Cramer, Daniel W; Cunningham, Julie M; Cybulski, Cezary; Plisiecka-Halasa, Joanna; Dennis, Joe; Dicks, Ed; Doherty, Jennifer A; Dörk, Thilo; du Bois, Andreas; Eccles, Diana; Easton, Douglas T; Edwards, Robert P; Eilber, Ursula; Ekici, Arif B; Fasching, Peter A; Fridley, Brooke L; Gao, Yu-Tang; Gentry-Maharaj, Aleksandra; Giles, Graham G; Glasspool, Rosalind; Goode, Ellen L; Goodman, Marc T; Gronwald, Jacek; Harter, Philipp; Hasmad, Hanis Nazihah; Hein, Alexander; Heitz, Florian; Hildebrandt, Michelle A T; Hillemanns, Peter; Hogdall, Estrid; Hogdall, Claus; Hosono, Satoyo; Jakubowska, Anna; Paul, James; Jensen, Allan; Karlan, Beth Y; Kjaer, Susanne Kruger; Kelemen, Linda E; Kellar, Melissa; Kelley, Joseph L; Kiemeney, Lambertus A; Krakstad, Camilla; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D; Lee, Alice W; Cannioto, Rikki; Leminen, Arto; Lester, Jenny; Levine, Douglas A; Liang, Dong; Lissowska, Jolanta; Lu, Karen; Lubinski, Jan; Lundvall, Lene; Massuger, Leon F A G; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R; Nevanlinna, Heli; McNeish, Iain; Menon, Usha; Modugno, Francesmary; Moysich, Kirsten B; Narod, Steven A; Nedergaard, Lotte; Ness, Roberta B; Noor Azmi, Mat Adenan; Odunsi, Kunle; Olson, Sara H; Orlow, Irene; Orsulic, Sandra; Pearce, Celeste L; Pejovic, Tanja; Pelttari, Liisa M; Permuth-Wey, Jennifer; Phelan, Catherine M; Pike, Malcolm C; Poole, Elizabeth M; Ramus, Susan J; Risch, Harvey A; Rosen, Barry; Rossing, Mary Anne; Rothstein, Joseph H; Rudolph, Anja; Runnebaum, Ingo B; Rzepecka, Iwona K; Salvesen, Helga B; Budzilowska, Agnieszka; Sellers, Thomas A; Shu, Xiao-Ou; Shvetsov, Yurii B; Siddiqui, Nadeem; Sieh, Weiva; Song, Honglin; Southey, Melissa C; Sucheston, Lara; Tangen, Ingvild L; Teo, Soo-Hwang; Terry, Kathryn L; Thompson, Pamela J; Timorek, Agnieszka; Tworoger, Shelley S; Van Nieuwenhuysen, Els; Vergote, Ignace; Vierkant, Robert A; Wang-Gohrke, Shan; Walsh, Christine; Wentzensen, Nicolas; Whittemore, Alice S; Wicklund, Kristine G; Wilkens, Lynne R; Woo, Yin-Ling; Wu, Xifeng; Wu, Anna H; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Coetzee, Gerhard A; Freedman, Matthew L; Monteiro, Alvaro N A; Moes-Sosnowska, Joanna; Kupryjanczyk, Jolanta; Pharoah, Paul D; Gayther, Simon A; Schildkraut, Joellen M

    2015-11-01

    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 genes and EOC risk. We genotyped 2896 common variants at 143 gene loci in DNA samples from 15 397 patients with invasive EOC and controls. We found evidence of associations with EOC risk for variants at FANCA, EXO1, E2F4, E2F2, CREB5 and CHEK2 genes (P ≤ 0.001). The strongest risk association was for CHEK2 SNP rs17507066 with serous EOC (P = 4.74 x 10(-7)). Additional genotyping and imputation of genotypes from the 1000 genomes project identified a slightly more significant association for CHEK2 SNP rs6005807 (r (2) with rs17507066 = 0.84, odds ratio (OR) 1.17, 95% CI 1.11-1.24, P = 1.1×10(-7)). We identified 293 variants in the region with likelihood ratios of less than 1:100 for representing the causal variant. Functional annotation identified 25 candidate SNPs that alter transcription factor binding sites within regulatory elements active in EOC precursor tissues. In The Cancer Genome Atlas dataset, CHEK2 gene expression was significantly higher in primary EOCs compared to normal fallopian tube tissues (P = 3.72×10(-8)). We also identified an association between genotypes of the candidate causal SNP rs12166475 (r (2) = 0.99 with rs6005807) and CHEK2 expression (P = 2.70×10(-8)). These data suggest that common variants at 22q12.1 are associated with risk of serous EOC and CHEK2 as a plausible target susceptibility gene. PMID:26424751

  4. Cigarette smoking and risk of borderline and invasive epithelial ovarian cancer.

    Science.gov (United States)

    Gram, Inger T; Braaten, Tonje; Adami, Hans-Olov; Lund, Eiliv; Weiderpass, Elisabete

    2008-02-01

    Studies regarding the association between smoking and risk of epithelial ovarian cancer (EOC) are inconsistent. The purpose of this study was to examine the association between smoking and EOC, overall and according to invasiveness and histological subtype in a cohort of women with a high proportion of smokers at enrollment. We followed 103,081 women, aged 30-50 years in 1991/1992, from the Norwegian-Swedish Women's Lifestyle and Health cohort. The women completed a questionnaire on personal characteristics and exposures at enrollment and were subsequently followed with linkages to national registers through December 31, 2004. We used Cox proportional hazard regression models to estimate hazard ratio (RR) of EOC with 95% confidence intervals (CIs) associated with different measures of smoking exposures adjusting for confounding variables. Altogether 343 [241 (70%) invasive and 102(30%) borderline] incident EOC cases were identified. Former [HR = 2.2(95% CI 1.0-4.7)] and current [HR = 2.7(95% CI 1.2-5.7)] smokers had a more than doubling in risk for borderline tumors compared to never smokers. Women who had smoked for more than 20 years had 3 times [HR = 3.1(95% CI 1.5-6.7)] the risk of borderline tumors compared to never smokers. A test for trend according to smoking status was almost significant for mucinous tumors (p-trend = 0.05). A significant dose response relationship was found according to smoking intensity [pack-years; (0-9, 0-14, >or= 15)] and duration [number of years; (0-10, 11-20, >or= 20)] for borderline and serous tumors (p-trends smoking may increase the risk of borderline EOC. PMID:17918152

  5. 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

    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...... 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....

  6. Hormonal risk factors and invasive epithelial ovarian cancer risk by parity

    OpenAIRE

    Bodelon, C; Wentzensen, N; Schonfeld, S. J.; Visvanathan, K; Hartge, P; Park, Y; Pfeiffer, R. M.

    2013-01-01

    Background: Recent studies have suggested that several ovarian cancer risk factors differ by parity status, but these findings have not been confirmed. We evaluated whether known risk factors of ovarian cancer differ between nulliparous and parous women using data from two large prospective cohorts. Methods: Data from the National Institutes of Health-AARP Diet and Health Study and the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial were combined for this analysis. Cox regressio...

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

    OpenAIRE

    Gifkins Dina; Olson Sara H; Paddock Lisa; King Melony; Demissie Kitaw; Lu Shou-En; Kong Ah-Ng; Rodriguez-Rodriguez Lorna; Bandera Elisa V

    2012-01-01

    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,...

  8. B-cell-specific Moloney murine leukemia virus integration site 1: potential stratification factor and therapeutic target for epithelial ovarian cancer

    Science.gov (United States)

    Zhao, Qianying; Gui, Ting; Qian, Qiuhong; Li, Lei; Shen, Keng

    2016-01-01

    Epithelial ovarian cancer, a vexing challenge for clinical management, still lacks biomarkers for early diagnosis, precise stratification, and prognostic evaluation of patients. B-cell-specific Moloney murine leukemia virus integration site 1 (BMI1), a member of the polycomb group of proteins, engages in diverse cellular processes, including proliferation, differentiation, senescence, and stem cell renewal. In addition, BMI1, as a cancer stem-cell marker, participates in tumorigenesis through various pathways. Rewardingly, recent studies have also revealed a relationship between BMI1 expression and the clinical grade/stage, therapy response, and survival outcome in a majority of human malignancies, including epithelial ovarian cancer. Therefore, BMI1 might serve as a potential stratification factor and treatment target for epithelial ovarian cancer, pending evidence from further investigations.

  9. B-cell-specific Moloney murine leukemia virus integration site 1: potential stratification factor and therapeutic target for epithelial ovarian cancer.

    Science.gov (United States)

    Zhao, Qianying; Gui, Ting; Qian, Qiuhong; Li, Lei; Shen, Keng

    2016-01-01

    Epithelial ovarian cancer, a vexing challenge for clinical management, still lacks biomarkers for early diagnosis, precise stratification, and prognostic evaluation of patients. B-cell-specific Moloney murine leukemia virus integration site 1 (BMI1), a member of the polycomb group of proteins, engages in diverse cellular processes, including proliferation, differentiation, senescence, and stem cell renewal. In addition, BMI1, as a cancer stem-cell marker, participates in tumorigenesis through various pathways. Rewardingly, recent studies have also revealed a relationship between BMI1 expression and the clinical grade/stage, therapy response, and survival outcome in a majority of human malignancies, including epithelial ovarian cancer. Therefore, BMI1 might serve as a potential stratification factor and treatment target for epithelial ovarian cancer, pending evidence from further investigations. PMID:27578986

  10. 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.

  11. 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.

  12. 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...

  13. Sugary food and beverage consumption and epithelial ovarian cancer risk: a population-based case–control study

    Science.gov (United States)

    2013-01-01

    Background Ovarian cancer is the deadliest gynecologic cancer in the US. The consumption of refined sugars has increased dramatically over the past few decades, accounting for almost 15% of total energy intake. Yet, there is limited evidence on how sugar consumption affects ovarian cancer risk. Methods We evaluated ovarian cancer risk in relation to sugary foods and beverages, and total and added sugar intakes in a population-based case–control study. Cases were women with newly diagnosed epithelial ovarian cancer, older than 21 years, able to speak English or Spanish, and residents of six counties in New Jersey. Controls met same criteria as cases, but were ineligible if they had both ovaries removed. A total of 205 cases and 390 controls completed a phone interview, food frequency questionnaire, and self-recorded waist and hip measurements. Based on dietary data, we computed the number of servings of dessert foods, non-dessert foods, sugary drinks and total sugary foods and drinks for each participant. Total and added sugar intakes (grams/day) were also calculated. Multiple logistic regression models were used to estimate odds ratios and 95% confidence intervals for food and drink groups and total and added sugar intakes, while adjusting for major risk factors. Results We did not find evidence of an association between consumption of sugary foods and beverages and risk, although there was a suggestion of increased risk associated with sugary drink intake (servings per 1,000 kcal; OR=1.63, 95% CI: 0.94-2.83). Conclusions Overall, we found little indication that sugar intake played a major role on ovarian cancer development. PMID:23442818

  14. [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.

  15. Whole abdominal irradiation following chemotherapy in advanced ovarian carcinoma

    International Nuclear Information System (INIS)

    One hundred and sixteen patients with advanced ovarian carcinoma, who underwent primary cytoreductive surgery, received 6-11 courses of chemotherapy by cis-platin (50 mg/m2) and adriamycin (50 mg/m2) every 21 days. This was followed by second look laparotomy in 66 patients with no clinical evidence of disease. Consolidation abdominal irradiation was administered to 43 patients. Two techniques of irradiation were employed: between 1980-1983 whole abdominal irradiation was used and patients were to receive 3000 cGy in 4 weeks (Schedule I). Due to myelosuppression only 13 of 26 patients (50%) completed the planned dose of radiation. Between 1983-1985 the target volume was divided into upper and lower parts. First, the lower abdomen received 3000 cGy in 3 weeks, and then the upper abdomen received the same dose (Schedule II). Sixteen of seventeen patients (94%) thus treated, completed the planned dose of radiation. The actuarial survival for all 116 patients was 28% of 5 years. Irradiated patients with negative second look laparotomy had a survival probability of 100% at 24 months. Irradiated patients with microscopic disease at second look operation had an actuarial 5-year survival of 66%. Patients with minimal residual disease at second look laparotomy, receiving consolidation abdominal irradiation, had an actuarial survival of 5% only at 36 months. It is concluded that consolidation radiotherapy is effective in patients with negative or microscopic residual disease at second-look laparotomy. In regard to bone marrow tolerance, split field technique of irradiation is preferred

  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. The next steps in improving the outcomes of advanced ovarian cancer.

    Science.gov (United States)

    Openshaw, Mark R; Fotopoulou, Christina; Blagden, Sarah; Gabra, Hani

    2015-06-01

    Worldwide ovarian cancer affects over 200,000 women per year. Overall survival rates are poor due to two predominate reasons. First, the majority of patients present with advanced disease creating significant difficulty with effecting disease eradication. Second, acquisition of chemotherapy resistance results in untreatable progressive disease. Advances in treatment of advanced ovarian cancer involve a spectrum of interventions including improvements in frontline debulking surgery and combination chemotherapy. Anti-angiogenic factors have been shown to have activity in frontline and recurrent disease while novel chemotherapeutic agents and targeted treatments are in development particularly for disease that is resistant to platinum-based chemotherapy. These developments aim to improve the progression-free and overall survival of women with advanced ovarian cancer. PMID:26102473

  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. Gene Set−Based Integrative Analysis Revealing Two Distinct Functional Regulation Patterns in Four Common Subtypes of Epithelial Ovarian Cancer

    Science.gov (United States)

    Chang, Chia-Ming; Chuang, Chi-Mu; Wang, Mong-Lien; Yang, Yi-Ping; Chuang, Jen-Hua; Yang, Ming-Jie; Yen, Ming-Shyen; Chiou, Shih-Hwa; Chang, Cheng-Chang

    2016-01-01

    Clear cell (CCC), endometrioid (EC), mucinous (MC) and high-grade serous carcinoma (SC) are the four most common subtypes of epithelial ovarian carcinoma (EOC). The widely accepted dualistic model of ovarian carcinogenesis divided EOCs into type I and II categories based on the molecular features. However, this hypothesis has not been experimentally demonstrated. We carried out a gene set-based analysis by integrating the microarray gene expression profiles downloaded from the publicly available databases. These quantified biological functions of EOCs were defined by 1454 Gene Ontology (GO) term and 674 Reactome pathway gene sets. The pathogenesis of the four EOC subtypes was investigated by hierarchical clustering and exploratory factor analysis. The patterns of functional regulation among the four subtypes containing 1316 cases could be accurately classified by machine learning. The results revealed that the ERBB and PI3K-related pathways played important roles in the carcinogenesis of CCC, EC and MC; while deregulation of cell cycle was more predominant in SC. The study revealed that two different functional regulation patterns exist among the four EOC subtypes, which were compatible with the type I and II classifications proposed by the dualistic model of ovarian carcinogenesis. PMID:27527159

  20. 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.

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

    International Nuclear Information System (INIS)

    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. 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). 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. 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

  2. Subtype specific elevated expression of hyaluronidase-1 (HYAL-1 in epithelial ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Paule Héléna Yoffou

    Full Text Available BACKGROUND: Epithelial ovarian cancer (EOC is morphologically heterogeneous being classified as serous, endometrioid, clear cell, or mucinous. Molecular genetic analysis has suggested a role for tumor suppressor genes located at chromosome 3p in serous EOC pathogenesis. Our objective was to evaluate the expression of HYAL1, located at chromosome 3p21.3, in these EOC subtypes, and to investigate its correlation with the expression of steroid hormone receptors. METHODOLOGY/PRINCIPAL FINDINGS: We determined the mRNA expression of HYAL1, estrogen receptor (ER-α, ERβ and progesterone receptor (PR in EOC tumor samples and cell lines using quantitative RT-PCR. We also examined the expression of these genes in a publicly available microarray dataset. HYAL-1 enzyme activity was measured in EOC cell lines and in plasma samples from patients. We found that HYAL1 mRNA expression was elevated in clear cell and mucinous EOC tissue samples, but not in serous and endometrioid samples, normal ovaries or benign tumors. Similar results were obtained by two different techniques and with tissue sample cohorts from two independent institutions. Concordantly, HYAL1 mRNA levels and enzymatic activity were elevated only in EOC cell lines derived from clear cell and mucinous subtypes. We also showed that HYAL1 mRNA was inversely correlated to that of ERα specifically in clear cell and mucinous EOCs. Additionally, ectopic expression of ERα in a clear cell EOC cell line (ER- and PR-negative induced 50% reduction of HYAL1 mRNA expression, supporting a role of ERα in HYAL1 gene regulation. Significantly, HYAL-1 activity was also high in the plasma of patients with these EOC subtypes. CONCLUSIONS/SIGNIFICANCE: This is the first report showing high HYAL-1 levels in EOC and demonstrating HYAL1 gene repression by ERα. Our results identify Hyaluronidase-1 as a potential target/biomarker for clear cell and mucinous EOCs and especially in tumors with low ERα levels.

  3. 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...

  4. Single Nucleotide Polymorphisms in the TP53 Region and Susceptibility to Invasive Epithelial Ovarian Cancer

    OpenAIRE

    Schildkraut, J M; Goode, E.L.; Clyde, M. A.; Iversen, E. S.; Moorman, P. G.; Berchuck, A.; Marks, J R; Lissowska, J; Brinton, L.; Peplonska, B.; Cunningham, J. M.; Vierkant, R A; Rider, D. N.; Chenevix-Trench, G; Webb, P M

    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 independ...

  5. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  8. 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

  9. 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...

  10. The effects of selenium on tumor growth in epithelial ovarian carcinoma

    OpenAIRE

    Park, Jin Sun; Ryu, Ji Yoon; Jeon, Hye-Kyung; Cho, Young Jae; Park, Young Ae; Choi, Jung-Joo; Lee, Jeong-Won; Kim, Byoung-Gie; Bae, Duk-Soo

    2012-01-01

    Objective Epidemiological studies suggest that selenium protects against the development of several cancers. Selenium (sodium selenite) has been reported to interfere with cell growth and proliferation, and to induce cell death. In this study, we tested whether selenium could have growth-inhibiting effect in ovarian cancer cells and an orthotopic animal model. Methods Cell growth in selenium-treated cells was determined in human ovarian cancer cells, A2780, HeyA8, and SKOV3ip1 using 3-(4,5-di...

  11. 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.

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

    International Nuclear Information System (INIS)

    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. 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). 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. 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

  13. Early pregnancy IGF-I and placental GH and risk of epithelial ovarian cancer: A nested case-control study.

    Science.gov (United States)

    Schock, Helena; Fortner, Renée T; Surcel, Heljä-Marja; Grankvist, Kjell; Pukkala, Eero; Lehtinen, Matti; Lundin, Eva

    2015-07-15

    Insulin-like growth factor-I (IGF-I) signaling may promote ovarian tumor development by exerting mitotic, antiapoptotic and proangiogenic effects. During pregnancy, maternal production of IGF-I is regulated by placental growth hormone (GH). Parity is an established protective factor for ovarian cancer, however, no prior study has evaluated placental GH and IGF-I in pregnancy and epithelial ovarian cancer (EOC). Prior prospective studies on the association between IGF-I and EOC in nonpregnant populations were inconclusive and did not address associations in subtypes of EOC. Among members of the Finnish Maternity Cohort and the Northern Sweden Maternity Cohort, we identified 1,045 EOC cases, diagnosed after recruitment (1975-2008) and before March 2011 and 2,658 individually matched controls. Placental GH and IGF-I were measured in serum from the last pregnancy before EOC diagnosis or selection as control. We used conditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for tertiles and a doubling of hormone concentrations. Higher IGF-I was associated with a nonsignificant decrease in risk for invasive [ORT3 vs. T1 : 0.79 (0.62-1.02); ptrend  = 0.07] and endometrioid tumors [ORT3 vs. T1 : 0.55 (0.28-1.07); ptrend  = 0.07]. The protective association between higher IGF-I levels and risk of invasive EOC was stronger in analyses limited to women aged study provides the first data on placental GH and IGF-I in pregnancy and EOC risk overall and by subtype. Our data suggest higher IGF-I levels in pregnancy may be associated with lower risk of invasive and endometrioid EOC. PMID:25516257

  14. Diethylstilbestrol regulates expression of avian apolipoprotein D during regression and recrudescence of the oviduct and epithelial-derived ovarian carcinogenesis.

    Science.gov (United States)

    Jeong, J; Bae, H; Lim, W; Bazer, F W; Song, G

    2015-07-01

    Apolipoprotein D (APOD) is a glycoprotein which is widely expressed in mammalian tissues. It is structurally and functionally similar to the lipocalins which are multiple lipid-binding proteins that transport hydrophobic ligands and other small hydrophobic molecules, including cholesterol and several steroid hormones. Although multiple functions for APOD in various tissues have been reported, its expression, biological function, and hormonal regulation in the female reproductive system are not known. Thus, in this study, we focused on correlations between APOD and estrogen during development, differentiation, regression, and regeneration of the oviduct in chickens and in the development of ovarian carcinogenesis in laying hens. Results of the present study indicated that APOD messenger RNA (mRNA) expression increased (P glandular (GE) epithelia of the chicken oviduct in response to diethylstilbestrol (a nonsteroidal synthetic estrogen). In addition, the expression of APOD mRNA and protein decreased (P < 0.001) as the oviduct regressed during induced molting, and gradually increased (P < 0.001) with abundant expression in GE of the oviduct during recrudescence after molting. Furthermore, APOD mRNA and protein were predominantly localized in GE of cancerous, but not normal ovaries from laying hens. Collectively, results of the present study suggest that APOD is a novel estrogen-stimulated gene in the chicken oviduct which likely regulates growth, differentiation, and remodeling of the oviduct during oviposition cycles. Moreover, up-regulated expression of APOD in epithelial cell-derived ovarian cancerous tissue suggests that it could be a candidate biomarker for early detection and treatment of ovarian cancer in laying hens and in women. PMID:25929245

  15. 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.

  16. 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.

  17. 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.

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

    LENUS (Irish Health Repository)

    Brennan, Donal J

    2010-01-01

    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.

  19. 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.

  20. [HE4, a novel marker for epithelial ovarian cancer: evaluation of analytical performances].

    Science.gov (United States)

    Lamy, Pierre-Jean; Roques, Sylvie; Viglianti, Cathy; Fabbro, Michel; Montels, Frédéric

    2010-01-01

    Human epididymis protein 4 (HE4) is a novel marker for ovarian cancer. HE4 exhibits a high sensitivity to detect ovarian cancer and can be used with CA125 as a predictor of malignancy. Additional uses of HE4 are as an aid of monitoring response to therapy for patients with invasive ovarian cancer and as a marker to detect recurrences in the follow-up after treatment of the primary tumor. The HE4 EIA, an enzyme immunoassay for the quantitative determination of HE4 in human serum developed by Fujirebio Diagnostic Inc. (Tokyo, Japan), is now available with a CE-IVD label in Europe (Diasource, Nivelles, Belgium). The aim of the study was to evaluate according to the COFRAC LAB GTA 04 guide, the analytical performance of the test, using 4 standardized samples (target values: 49.8, 140.4, 167.6 and 415.2 pmol/L) and serum samples from patients with ovarian cancer treated in our institution. Intra- and inter-assay precisions showed coefficients of variation less than 10%. The low limit of detection (4 pmol/L) and the limit of quantitation (8 pmol/L) are suitable for clinical samples assessment. The assay mean dilution linearity is 100 +/- 10% (90 to 107% of recovery). Globally, the uncertainty varied from 13.1% (low values) to 28.1% (elevated values). We conclude that the HE4 EIA from Fujirebio Diagnostic Inc. displayed convenient analytical performances that allows its use it clinical practice.

  1. 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...

  2. Targeting Nrf2 in healthy and malignant ovarian epithelial cells : Protection versus promotion

    NARCIS (Netherlands)

    van der Wijst, Monique G. P.; Huisman, Christian; Mposhi, Archibold; Roelfes, Gerard; Rots, Marianne G.

    2015-01-01

    Risk factors indicate the importance of oxidative stress during ovarian carcinogenesis. To tolerate oxidative stress, cells activate the transcription factor Nrf2 (Nfe2l2), the master regulator of antioxidant and cytoprotective genes. Indeed, for most cancers, hyperactivity of Nrf2 is observed, and

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

    NARCIS (Netherlands)

    Pharoah, P.D.; Palmieri, R.T.; Ramus, S.J.; Gayther, S.A.; Andrulis, I.L.; Anton-Culver, H.; Antonenkova, N.; Antoniou, A.C.; Goldgar, D.; Beattie, M.S.; Beckmann, M.W.; Birrer, M.J.; Bogdanova, N.; Bolton, K.L.; Brewster, W.; Brooks-Wilson, A.; Brown, R.; Butzow, R.; Caldes, T.; Caligo, M.A.; Campbell, I.; Chang-Claude, J.; Chen, Y.A.; Cook, L.S.; Couch, F.J.; Cramer, D.W; Cunningham, J.M.; Despierre, E.; Doherty, J.A.; Dork, T.; Durst, M.; Eccles, D.M.; Ekici, A.B.; Easton, D.; Fasching, P.A.; Fazio, A. de; Fenstermacher, D.A.; Flanagan, J.M.; Fridley, B.L.; Friedman, E.; Gao, B.; Sinilnikova, O.; Gentry-Maharaj, A.; Godwin, A.K.; Goode, E.L.; Goodman, M.T.; Gross, J.; Hansen, T.V.; Harnett, P.; Rookus, M.; Heikkinen, T.; Hein, R.; Hogdall, C.; Hogdall, E.; Iversen, E.S.; Jakubowska, A.; Johnatty, S.E.; Karlan, B.Y.; Kauff, N.D.; Kaye, S.B.; Chenevix-Trench, G.; Kelemen, L.E.; Kiemeney, L.A.L.M.; Kjaer, S.K.; Lambrechts, D.; Lapolla, J.P.; Lazaro, C.; Le, N.D.; Leminen, A.; Leunen, K.; Levine, D.A.; Lu, Y.; Lundvall, L.; MacGregor, S.; Marees, T.; Massuger, L.F.A.G.; McLaughlin, J.R.; Menon, U.; Montagna, M.; Moysich, K.B.; Narod, S.A.; Nathanson, K.L.; Nedergaard, L.; Ness, R.B.; Nevanlinna, H.; Nickels, S.; Osorio, A.; Paul, J.; Pearce, C.L.; Phelan, C.M.; Pike, M.C.; Radice, P.; Rossing, M.A.; Schildkraut, J.M.; Sellers, T.A.; Singer, C.F.; Song, H.; Stram, D.O.; Sutphen, R.; Lindblom, A.

    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 candi

  4. 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...

  5. 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.

  6. 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.

  7. Cross-sectional study on comorbidities and adverse events in patients with advanced and recurrent ovarian cancer in France

    Directory of Open Access Journals (Sweden)

    Le Saux O

    2015-10-01

    Full Text Available Olivia Le Saux,1 Aliki Taylor,2 Victoria Chia,3 Demetris Pillas,2 Moninder Kaur,2 Gilles Freyer11Department of Medical Oncology, Centre Hospitalier Lyon-Sud, Pierre-Bénite Cédex, France; 2Center for Observational Research, Amgen Ltd, Uxbridge, UK; 3Center for Observational Research, Amgen Inc., Thousand Oaks, CA, USA Purpose: The purpose of this study was to evaluate the prevalence of comorbidities and adverse events (AEs, and determine the treatment patterns according to platinum-sensitivity status in patients with advanced (stage IIIB–IV or recurrent epithelial ovarian cancer (EOC. Methods: A cross-sectional study was carried out in France with patients over 18 years, diagnosed with advanced (stage IIIB–IV or recurrent EOC between 2009 and 2012. A total of 23 physicians (oncologists and gynecologists participated, contributing 127 patients. Data were abstracted by participating physicians into a case report form. Results: Of the 127 patients included, 92 (72.4% had advanced EOC and 35 (27.6% had recurrent EOC. A total of 73 comorbidities were reported in 44 patients (34.6%. Vascular (10.2%, metabolic (7.1%, respiratory (5.5%, and psychiatric disorders (5.5% were the most common types of comorbidities reported. Prevalence of AEs was 74.8%, of which 12.6% were classified as serious. The most common AEs were anemia (16.5%, hematologic events (12.6%, taste change (11.8%, and headache (7.1%. Throughout the follow-up period, twelve patient deaths were reported (six due to disease progression. Of 35 patients with recurrent disease, 16 were highly platinum sensitive (recurrence >12 months after stopping platinum-based therapy, eleven were partially platinum sensitive (recurrence 6–12 months after stopping platinum-based therapy, seven were platinum resistant (recurrence within 6 months of stopping platinum-based therapy or progression while receiving second- or later-line platinum-based therapy, and one was platinum refractory (recurrence

  8. 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

  9. 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.

  10. Regulatory T cells, inherited variation, and clinical outcome in epithelial ovarian cancer.

    Science.gov (United States)

    Knutson, Keith L; Maurer, Matthew J; Preston, Claudia C; Moysich, Kirsten B; Goergen, Krista; Hawthorne, Kieran M; Cunningham, Julie M; Odunsi, Kunle; Hartmann, Lynn C; Kalli, Kimberly R; Oberg, Ann L; Goode, Ellen L

    2015-12-01

    The immune system constitutes one of the host factors modifying outcomes in ovarian cancer. Regulatory T cells (Tregs) are believed to be a major factor in preventing the immune response from destroying ovarian cancers. Understanding mechanisms that regulate Tregs in the tumor microenvironment could lead to the identification of novel targets aimed at reducing their influence. In this study, we used immunofluorescence-based microscopy to enumerate Tregs, total CD4 T cells, and CD8(+) cytotoxic T cells in fresh frozen tumors from over 400 patients with ovarian cancer (>80 % high-grade serous). We sought to determine whether Tregs were associated with survival and genetic variation in 79 genes known to influence Treg induction, trafficking, or function. We used Cox regression, accounting for known prognostic factors, to estimate hazard ratios (HRs) associated with T cell counts and ratios. We found that the ratios of CD8 T cells and total CD4 T cells to Tregs were associated with improved overall survival (CD8/Treg HR 0.84, p = 0.0089; CD4/Treg HR 0.88, p = 0.046) and with genetic variation in IL-10 (p = 0.0073 and 0.01, respectively). In multivariate analyses, the associations between the ratios and overall survival remained similar (IL-10 and clinical covariate-adjusted CD8/Treg HR 0.85, p = 0.031; CD4/Treg HR 0.87, p = 0.093), suggesting that this association was not driven by variation in IL-10. Thus, integration of novel tumor phenotyping measures with extensive clinical and genetic information suggests that the ratio of T cells to Tregs may be prognostic of outcome in ovarian cancer, regardless of inherited genotype in genes related to Tregs. PMID:26298430

  11. 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.

  12. Metastatic dissemination of human ovarian epithelial carcinoma is promoted by alpha2beta1-integrin-mediated interaction with type I collagen.

    Science.gov (United States)

    Fishman, D A; Kearns, A; Chilukuri, K; Bafetti, L M; O'Toole, E A; Georgacopoulos, J; Ravosa, M J; Stack, M S

    1998-01-01

    Metastatic dissemination of epithelial ovarian carcinoma is thought to be mediated via tumor cell exfoliation into the peritoneal cavity, followed by adhesion to and invasion through the mesothelium which overlies the contents of the peritoneal cavity. In this study, we have utilized short-term primary cultures to analyze the effect of specific extracellular matrix proteins on properties of human ovarian epithelial carcinoma cells which contribute to the invasive phenotype. Analysis of cell:matrix adhesive profiles indicated that ovarian carcinoma cells adhere preferentially to type I collagen. Immunoprecipitation analyses demonstrated the presence of the collagen-binding alpha2beta1 integrin in biotin-labeled ovarian carcinoma cell membranes, and cellular adhesion was inhibited by blocking antibodies directed against the alpha2 and beta1 integrin subunits. The alpha2beta1-binding peptide Asp-Gly-Glu-Ala (DGEA) was also moderately effective at blocking adhesion to collagen relative to the control peptide Ala-Gly-Glu-Ala (AGEA). Analysis of cell motility on protein-coated colloidal gold coverslips demonstrated that ovarian carcinoma cells migrate preferentially on type I collagen coated surfaces. Type I collagen promoted migration in a concentration-dependent, saturable manner, with maximal migration observed at a collagen-coating concentration of 50 microg/ml. Migration on collagen was inhibited by antibodies directed against the alpha2 and beta1 integrin subunits and by DGEA peptide, providing evidence for the role of the alpha2beta1 integrin in ovarian carcinoma cell motility. Culturing ovarian carcinoma cells on type I collagen gels led to a significant increase in conversion of the matrix metalloproteinase 2 zymogen to the 66-kD form, suggesting that adhesion to collagen also influences matrix-degrading proteinases. These data suggest that alpha2beta1-integrin-mediated interaction of ovarian carcinoma cells with type I collagen, a protein prevalent both in the

  13. 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.

  14. 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

    Background: The addition of anthracyclines to platinum-based chemotherapy may provide benefit in survival in ovarian cancer patients. We evaluated the effect on survival of adding epirubicin to standard carboplatin and paclitaxel. Patients and methods: We carried out a prospectively randomized...... 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...... addition of epirubicin to standard carboplatin and paclitaxel treatment did not improve survival in patients with advanced ovarian, tubal or peritoneal cancer....

  15. B-cell-specific Moloney murine leukemia virus integration site 1: potential stratification factor and therapeutic target for epithelial ovarian cancer

    OpenAIRE

    Zhao, Qianying; Gui, Ting; Qian, Qiuhong; Li, Lei; Shen, Keng

    2016-01-01

    Qianying Zhao,1,* Ting Gui,1,* Qiuhong Qian,1,2 Lei Li,1 Keng Shen1 1Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 2Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Shandong, People’s Republic of China *These authors contributed equally to this work Abstract: Epithelial ovarian cancer, a vexing challenge for clinical management, stil...

  16. 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

  17. 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

  18. 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

  19. Effects of HLEC on the secreted proteins of epithelial ovarian cancer cells prone to metastasize to lymph nodes

    Institute of Scientific and Technical Information of China (English)

    Xin-Ying Zhang; Fu-Qiang Yin; Li Liu; Ting Gao; He-Yun Ruan; Xiao Guan; Ying-Xin Lu; Dan-Rong Li

    2013-01-01

    Objective:To study explores the effect of HLEC on the secreted proteins of epithelial ovarian cancer (EOC) cells (SKOV3-PM4) with directional highly lymphatic metastasis. Methods:Supernatants of four groups of cultured cells, namely, SKOV3 (A), SKOV3+HLEC (B), SKOV3-PM4 (C), SKOV3-PM4+HLEC (D), were collected, and their proteins were detected by antibody arrays and iTARQ-2D-LC-MALDI-TOF/TOF/MS. Signiifcantly differential proteins were further analyzed via bioinformatics and validated in human serums and cell media via ELISA. Results:Results of antibody arrays and mass spectrometry demonstrated that GRN and VEGFA were upregulated in group C (compared with group A), whereas IGFBP7 and SPARC were downregulated in group D (compared with group C). Comprehensive bioinformatics analysis results showed that IGFBP7 and VEGFA were closely linked to each other. Further validation with serums showed statistical signiifcance in VEGFA and IGFBP7 levels among groups of patients with ovarian cancers, benign tumors, and control groups. Two proteins were upegulated in the ifrst group. VEGFA in the control group was downregulated. For IGFBP, upregulation in the control group and down-regulation in the ifrst group were also observed. Conclusion:The HLEC microenvironment is closely associated with directional metastasis to lymph nodes and with differential proteins including cell stromal proteins and adhesion factors. hTe upregulation of VEGFA and GRN and the downregulation of SPARC and IGFBP7 are closely associated with directional metastasis to lymph nodes in EOC cells.

  20. 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.

  1. 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

  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. Advances in ovarian cancer diagnosis: A journey from immunoassays to immunosensors.

    Science.gov (United States)

    Sharma, Shikha; Raghav, Ragini; O'Kennedy, Richard; Srivastava, Sudha

    2016-07-01

    This review focuses on the technological advancements, challenges and trends in immunoassay technologies for ovarian cancer diagnosis. Emphasis is placed on the principles of the technologies, their merits and limitations and on the evolution from laboratory-based methods to point-of-care devices. While the current market is predominantly associated with clinical immunoassay kits, over the last decade a major thrust in development of immunosensors is evident due to their potential in point-of-care devices. Technological advancements in immunosensors, extending from labeled to label-free detection, with and without mediators, for enhancing proficiencies and reliability have been dealt with in detail. Aspects of the utilisation of nanomaterials and immobilization strategies for enhancing sensitivity and altering the detection range have also been addressed. Finally, we have discussed some distinct characteristics and limitations associated with the recently commericalised technologies used for quantitation of relevant ovarian cancer markers. PMID:27233124

  4. 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.

  5. 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

  6. Primary Surgery or Neoadjuvant Chemotherapy in Advanced Ovarian Cancer: The Debate Continues….

    Science.gov (United States)

    Leary, Alexandra; Cowan, Renee; Chi, Dennis; Kehoe, Sean; Nankivell, Matthew

    2016-01-01

    Primary debulking surgery (PDS) followed by platinum-based chemotherapy has been the cornerstone of treatment for advanced ovarian cancer for decades. Primary debulking surgery has been repeatedly identified as one of the key factors in improving survival in patients with advanced ovarian cancer, especially when minimal or no residual disease is left behind. Achieving these results sometimes requires extensive abdominal and pelvic surgical procedures and consultation with other surgical teams. Some clinicians who propose a primary chemotherapy approach reported an increased likelihood of leaving no macroscopic disease after surgery and improved patient-reported outcomes and quality-of-life (QOL) measures. Given the ongoing debate regarding the relative benefit of PDS versus neoadjuvant chemotherapy (NACT), tumor biology may aid in patient selection for each approach. Neoadjuvant chemotherapy offers the opportunity for in vivo chemosensitivity testing. Studies are needed to determine the best way to evaluate the impact of NACT in each individual patient with advanced ovarian cancer. Indeed, the biggest utility of NACT may be in research, where this approach provides the opportunity for the investigation of predictive markers, mechanisms of resistance, and a forum to test novel therapies. PMID:27249696

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

    DEFF Research Database (Denmark)

    Chornokur, Ganna; Lin, Hui-Yi; Tyrer, Jonathan P;

    2015-01-01

    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 qcancers combined and for the serous subtype was observed for SNP rs17216603 in the iron......BACKGROUND: 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...

  9. IGFBP-4 tumor and serum levels are increased across all stages of epithelial ovarian cancer

    Directory of Open Access Journals (Sweden)

    Mosig Rebecca A

    2012-01-01

    Full Text Available Abstract Background We sought to identify candidate serum biomarkers for the detection and surveillance of EOC. Based on RNA-Seq transcriptome analysis of patient-derived tumors, highly expressed secreted proteins were identified using a bioinformatic approach. Methods RNA-Seq was used to quantify papillary serous ovarian cancer transcriptomes. Paired end sequencing of 22 flash frozen tumors was performed. Sequence alignments were processed with the program ELAND, expression levels with ERANGE and then bioinformatically screened for secreted protein signatures. Serum samples from women with benign and malignant pelvic masses and serial samples from women during chemotherapy regimens were measured for IGFBP-4 by ELISA. Student's t Test, ANOVA, and ROC curves were used for statistical analysis. Results Insulin-like growth factor binding protein (IGFBP-4 was consistently present in the top 7.5% of all expressed genes in all tumor samples. We then screened serum samples to determine if increased tumor expression correlated with serum expression. In an initial discovery set of 21 samples, IGFBP-4 levels were found to be elevated in patients, including those with early stage disease and normal CA125 levels. In a larger and independent validation set (82 controls, 78 cases, IGFBP-4 levels were significantly increased (p -5. IGFBP-4 levels were ~3× greater in women with malignant pelvic masses compared to women with benign masses. ROC sensitivity was 73% at 93% specificity (AUC 0.816. In women receiving chemotherapy, average IGFBP-4 levels were below the ROC-determined threshold and lower in NED patients compared to AWD patients. Conclusions This study, the first to our knowledge to use RNA-Seq for biomarker discovery, identified IGFBP-4 as overexpressed in ovarian cancer patients. Beyond this, these studies identified two additional intriguing findings. First, IGFBP-4 can be elevated in early stage disease without elevated CA125. Second, IGFBP-4

  10. 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.

  11. SNAIL gene inhibited by hypoxia-inducible factor 1α (HIF-1α) in epithelial ovarian cancer.

    Science.gov (United States)

    Zhang, Pengnan; Liu, Yanmei; Feng, Youji; Gao, Shujun

    2016-09-01

    The aim of this study was to investigate the relationship between HIF-1α and SNAIL gene expression in the epithelial ovarian cancer (EOC) cell line. EOC cells were treated with hypoxia, hypoxia combined with rapamycin, and control. The expression of HIF-1α and E-cad were assessed by reverse transcription-polymerase chain reaction (RT-PCR) and western blotting. The gene expression of SNAIL was studied by RT-PCR and real-time PCR. RNA interference technology was used to determine the relationship between HIF-1α and SNAIL. The present study indicated that the HIF-1α protein was expressed and increased in EOC cell line. SNAIL mRNA was found to increase and E-cad expression decreased with the time of hypoxia prolonged. Hypoxia increased invasion abilities of EOC cell line, but compared with cells exposed to hypoxia, the change of invasive ability of cells with rapamycin had no effect. The expression of HIF-1α protein and SNAIL mRNA could be inhibited gradually by rapamycin. siRNA of HIF-1α could suppress the expression of SNAIL while siRNA of SNAIL had no influence on HIF-1α protein expression. HIF-1α may be the upstream of the SNAIL gene in EOC. Our data suggested that HIF-1α might be an upregulator of the SNAIL gene and HIF-1α-SNAIL-E-cad pathway may play an important role in EOC invasion and metastasis. PMID:27044634

  12. A method to evaluate genome-wide methylation in archival formalin-fixed, paraffin-embedded ovarian epithelial cells.

    Directory of Open Access Journals (Sweden)

    Qiling Li

    Full Text Available BACKGROUND: The use of DNA from archival formalin and paraffin embedded (FFPE tissue for genetic and epigenetic analyses may be problematic, since the DNA is often degraded and only limited amounts may be available. Thus, it is currently not known whether genome-wide methylation can be reliably assessed in DNA from archival FFPE tissue. METHODOLOGY/PRINCIPAL FINDINGS: Ovarian tissues, which were obtained and formalin-fixed and paraffin-embedded in either 1999 or 2011, were sectioned and stained with hematoxylin-eosin (H&E.Epithelial cells were captured by laser micro dissection, and their DNA subjected to whole genomic bisulfite conversion, whole genomic polymerase chain reaction (PCR amplification, and purification. Sequencing and software analyses were performed to identify the extent of genomic methylation. We observed that 31.7% of sequence reads from the DNA in the 1999 archival FFPE tissue, and 70.6% of the reads from the 2011 sample, could be matched with the genome. Methylation rates of CpG on the Watson and Crick strands were 32.2% and 45.5%, respectively, in the 1999 sample, and 65.1% and 42.7% in the 2011 sample. CONCLUSIONS/SIGNIFICANCE: We have developed an efficient method that allows DNA methylation to be assessed in archival FFPE tissue samples.

  13. 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.

  14. 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.

  15. Comparison of prognoses according to non-positive and positive spectrin αII expression detected immunohistochemically in epithelial ovarian carcinoma: a retrospective study.

    Science.gov (United States)

    Maeda, Osamu; Miyata-Takata, Tomoko; Shibata, Kiyosumi; Kajiyama, Hiroaki; Mizuno, Mika; Tamakoshi, Koji; Shimoyama, Yoshie; Nakamura, Shigeo; Kikkawa, Fumitaka

    2016-06-01

    Anticancer drug sensitivity affects prognosis in ovarian carcinoma. Previously, we purified spectrin αII and βII tetramers from cisplatin-resistant ovarian serous adenocarcinoma cells and demonstrated that they contribute to platinum anticancer drug resistance. In this clinical study, we focused on the role of spectrin αII expression. It is our objective to demonstrate the potential of spectrin αII expression as a useful predictor of anticancer drug resistance and postoperative prognosis in epithelial ovarian carcinoma. Spectrin αII expression in the ovarian adenocarcinoma surgical specimens of 193 patients was examined by immunohistochemical staining. Staining strength was scored 3+, regarded as positive expression, and 2+, 1+, and 0, regarded as non-positive expression. Prognoses obtained from clinical records were evaluated by statistical analysis. In the 193 cases studied, positive spectrin αII expression was associated with worse overall survival when compared with non-positive expression (P spectrin αII expression was identified as an independent predictive factor of overall survival (hazard ratio[HR]: 3.77, 95% confidence interval[CI]: 1.77-8.00; P spectrin αII expression was not associated with prognoses. However, similar results as overall survival were obtained for survival after recurrence of the 92 recurrent cases (P = 0.0051 by log-rank test, HR: 4.49, 95% CI: 2.06-9.79; P Spectrin αII expression is a useful predictor of anticancer drug resistance and postoperative prognosis in epithelial ovarian carcinoma.. PMID:26993048

  16. Phase II study evaluating consolidation whole abdominal intensity-modulated radiotherapy (IMRT) in patients with advanced ovarian cancer stage FIGO III - The OVAR-IMRT-02 Study

    International Nuclear Information System (INIS)

    The prognosis for patients with advanced FIGO stage III epithelial ovarian cancer remains poor despite the aggressive standard treatment, consisting of maximal cytoreductive surgery and platinum-based chemotherapy. The median time to recurrence is less than 2 years, with a 5-years survival rate of -20-25%. Recurrences of the disease occur mostly intraperitoneally. Ovarian cancer is a radiosensitive tumor, so that the use of whole abdominal radiotherapy (WAR) as a consolidation therapy would appear to be a logical strategy. WAR used to be the standard treatment after surgery before the chemotherapy era; however, it has been almost totally excluded from the treatment of ovarian cancer during the past decade because of its high toxicity. Modern intensity-modulated radiation therapy (IMRT) has the potential of sparing organs at risk like kidneys, liver, and bone marrow while still adequately covering the peritoneal cavity with a homogenous dose. Our previous phase I study showed for the first time the clinical feasibility of intensity-modulated WAR and pointed out promising results concerning treatment tolerance. The current phase-II study succeeds to the phase-I study to further evaluate the toxicity of this new treatment. The OVAR-IMRT-02 study is a single-center one arm phase-II trial. Thirty seven patients with optimally debulked ovarian cancer stage FIGO III having a complete remission after chemotherapy will be treated with intensity-modulated WAR as a consolidation therapy. A total dose of 30 Gy in 20 fractions of 1.5 Gy will be applied to the entire peritoneal cavity including the liver surface and the pelvic and para-aortic node regions. Organ at risk are kidneys, liver (except the 1 cm-outer border), heart, vertebral bodies and pelvic bones. Primary endpoint is tolerability; secondary objectives are toxicity, quality of life, progression-free and overall survival. Intensity-modulated WAR provides a new promising option in the consolidation treatment of

  17. Epithelial-mesenchymal transition-associated miRNAs in ovarian carcinoma, with highlight on the miR-200 family: prognostic value and prospective role in ovarian cancer therapeutics.

    Science.gov (United States)

    Koutsaki, Maria; Spandidos, Demetrios A; Zaravinos, Apostolos

    2014-09-01

    MicroRNAs (miRNAs) are a family of short ribonucleic acids found to play a pivotal role in cancer pathogenesis. MiRNAs are crucial in cellular differentiation, growth, stress response, cell death and other fundamental cellular processes, and their involvement in ovarian cancer has been recently shown. They can repress the expression of important cancer-related genes and they can also function both as oncogenes and tumour suppressor genes. During epithelial-mesenchymal transition (EMT), epithelial cells lose their cell polarity and cell-cell adhesion and gain migratory and invasive properties. In the ovarian surface epithelium, EMT is considered the key regulator of the post-ovulatory repair process and it can be triggered by a range of environmental stimuli. The aberrant expression of the miR-200 family (miR-200a, miR-200b, miR-200c, miR-141 and miR-429) in ovarian carcinoma and its involvement in ovarian cancer initiation and progression has been well-demonstrated. The miR-200 family members seem to be strongly associated with a pathologic EMT and to have a metastasis suppressive role. MiRNA signatures can accurately distinguish ovarian cancer from the normal ovary and can be used as diagnostic tools to predict the clinical response to chemotherapy. Recent evidence suggests a growing list of new miRNAs (miR-187, miR-34a, miR-506, miRNA-138, miR-30c, miR-30d, miR-30e-3p, miR-370 and miR-106a, among others) that are also implicated in ovarian carcinoma-associated EMT, either enhancing or suppressing it. MiRNA-based gene therapy provides a prospective anti-tumour approach for integrated cancer therapy. The aim of nanotechnology-based delivery approach for miRNA therapy is to overcome challenges in miRNA delivery and to effectively encourage the reprogramming of miRNA networks in cancer cells, which may lead to a clinically translatable miRNA-based therapy to benefit ovarian cancer patients. PMID:24952258

  18. Primary debulking surgery or neoadjuvant chemotherapy followed by interval debulking surgery for patients with advanced ovarian cancer

    Institute of Scientific and Technical Information of China (English)

    Hong Zheng; Yu-Nong Gao

    2012-01-01

    Objectives:To compare the survival and perioperative morbidity between primary debulking surgery (PDS) and neoadjuvant chemotherapy followed by interval debulking surgery (NAC/IDS) in treating patients with advanced epithelial ovarian cancer (EOC).Methods:We retrospectively reviewed 67 patients with stage ⅢC or Ⅳ EOC treated at Peking University Cancer Hospital from January 2006 to June 2009.Wherein,37 and 30 patients underwent PDS and NAC/IDS,respectively.Results:No difference in overall survival (OS) or progression-free survival (PFS) was observed between NAC/IDS group and PDS group (OS:41.2 vs.39.1 months,P=0.23; PFS:27.1 vs.24.3 months,P=0.37).The optimal debulking rate was 60% in the NAC/IDS group,which was significantly higher than that in the PDS group (32.4%) (P=0.024).The NAC/IDS group had significantly less intraoperative estimated blood loss and transfusion,lower nasogastric intubation rate,and earlier ambulation and recovery of intestinal function than the PDS group (P<0.05).Conclusions:NAC/IDS is less invasive than PDS,and offers the advantages regarding optimal cytoreduction rate,intraoperative blood loss,and postoperative recovery,without significantly impairing the survival compared with PDS in treating patients with stage ⅢC or Ⅳ EOC.Therefore,NAC/IDS may be a valuable treatment alternative for EOC patients.

  19. Validation of LRG1 as a potential biomarker for detection of epithelial ovarian cancer by a blinded study.

    Directory of Open Access Journals (Sweden)

    Jing Wu

    Full Text Available Leucine-rich alpha-2-glycoprotein (LRG1 was found to be differentially expressed in sera from patients with Epithelial Ovarian Cancer (EOC. The aim of this study is to investigate the performance of LRG1 for detection of EOC, including early stage EOC, and to evaluate if LRG1 can complement CA125 in order to improve EOC detection using two independent blinded sample sets.Serum LRG1 and CA125 were measured by immunoassays. All assays were performed blinded to clinical data. Using the two independent sample sets (156 participants for sample set 1, and 233 for sample set 2, LRG1 was differentially expressed in EOC cases as compared to healthy, surgical, and benign controls, and its performance was not affected by the conditions of blood collection. The areas under the ROC curve (AUC for LRG1 in differentiating EOC cases from non-cases were 0.797 and 0.786 for sample set 1 and 2. For differentiating EOC cases from healthy controls, the AUC values for LRG1 were 0.792 and 0.794. At a fixed specificity of 95%, LRG1 detects 52%, and 53.5% of EOC cases from healthy controls for sample set 1 and 2. When combining LRG1 and CA125, the AUC value increased to 0.927, which was improved compared to CA125 (AUC=0.916 (p=0.008 alone in distinguishing EOC cases from non-cases. More importantly, LRG1 also showed potential performance in differentiating early stage EOC from non-cases with an AUC of 0.715 for sample set 1, and 0.690 for sample set 2. The combination of LRG1 and CA125 resulted in an AUC of 0.838, which outperforms CA125 (AUC=0.785 (p=0.018 in detecting early stage EOC cases from non-cases using the larger sample set.LRG1 could be a useful biomarker alone or in combination with CA125 for the diagnosis of ovarian cancer.

  20. 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.

  1. Burkitt’s Lymphoma Presented as Advanced Ovarian Cancer without Evidence of Lymphadenopathy: CT and MRI Findings

    OpenAIRE

    Lucia Manganaro; Silvia Bernardo; Maria Eleonora Sergi; Paolo Sollazzo; Valeria Vinci; Alessandra De Grazia; Anna Clerico; Maria Giovanna Mollace; Matteo Saldari

    2013-01-01

    Burkitt's lymphoma is a rare non-Hodgkin's lymphoma which can occasionally involve the ovary and may cause confusion for the clinician since its presentation might mimic other much more frequent tumors. We present a case of a 23-year-old woman with sporadic Burkitt’s lymphoma presented as advanced ovarian cancer with bilateral ovarian masses, peritoneal carcinomatosis, ascites, and marked elevation of CA-125. Liver involvement and atypical bone lesions, such as the cranial vault and the ili...

  2. 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.

  3. 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.

  4. 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.)

  5. 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.

  6. Progress in study on etiology of ovarian epithelial cancer%上皮性卵巢癌病因学研究进展

    Institute of Scientific and Technical Information of China (English)

    纪晓宁; 丰有吉

    2014-01-01

    Epithelial ovarian cancer, which is one of the most lethal gynecological tumors, is also the biggest dififculty in the diagnosis and treatment of obstetrics and gynecology. In addition to the lack of early clinical symptoms and effective diagnostic methods, the reason includes the lack of accurate and comprehensive understanding of the development of epithelial ovarian cancer. Thus a lot of research aimed at better grasp of its pathogenesis, which is expected in the future progress of its diagnosis and treatment. Currently, three pathogenesis of epithelial ovarian cancer widely accepted are high gonadotropin theory, “dualism” hypothesis and stem cell hypothesis. This study discussed the theory above.%上皮性卵巢癌是当今最致命的妇科肿瘤之一,也是妇产科临床诊断及治疗中的最大难点。究其原因,除了早期缺乏明显的临床症状及有效的诊断方法外,还由于缺乏对上皮性卵巢癌发生、发展准确而全面的认识,故相关研究旨在更好地掌握上皮性卵巢癌的发病机制,有望在今后的诊断及治疗中取得新的进展。目前,上皮性卵巢癌公认的三大发病机制是:高促性腺激素理论、“二元论”和干细胞假说。本文对此作一综述。

  7. Temsirolimus, Carboplatin, and Paclitaxel in Treating Patients With Advanced Solid Tumors

    Science.gov (United States)

    2014-06-18

    Ovarian Sarcoma; Ovarian Stromal Cancer; Recurrent Endometrial Carcinoma; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Stage III Endometrial Carcinoma; Stage III Ovarian Epithelial Cancer; Stage III Ovarian Germ Cell Tumor; Stage IV Endometrial Carcinoma; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Unspecified Adult Solid Tumor, Protocol Specific

  8. 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.

  9. A rare case of ovarian cancer in pregnancy complicated by pulmonary embolus and myocardial infarction: management dilemmas

    OpenAIRE

    Nasser, Sara; von Heymann, Christian; Feldheiser, Aarne; Schäfer-Graf, Ute; Klempert, Iris; Pöllinger, Alexander; Krackhardt, Florian; Henrich, Wolfgang; Sehouli, Jalid; Pietzner, Klaus

    2014-01-01

    Malignant ovarian neoplasms diagnosed during pregnancy at advanced stages are very rare. The clinical course and prognosis of pregnant patients diagnosed with epithelial ovarian cancer is similar to that of non-pregnant patients. We describe our management of a woman diagnosed with FIGO IIIc ovarian cancer at Caesarean section. Immediately after surgery she suffered a pulmonary embolus and a myocardial infarction. She showed signs of a severe pulmonary hypertension (59 mmHg). Four weeks later...

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

    International Nuclear Information System (INIS)

    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

  11. 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

    the Ovarian Cancer Association Consortium. The fixed effects estimate per rs17647532 allele was null (odds ratio, 0.99; 95% confidence interval, 0.92-1.07). When a recessive model was fit, the results were unchanged. Test for heterogeneity of the odds ratios revealed consistency across the 14 replication......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 polymorphism...... in the UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltransferase, GALNT1, had decreased ovarian cancer risk. The current study attempted to replicate this observation. The GALNT1 single-nucleotide polymorphism rs17647532 was genotyped in 6,965 cases and 8,377 controls from 14 studies forming...

  12. 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....

  13. 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

    We used a functional complementation approach to identify tumor-suppressor genes and putative therapeutic targets for ovarian cancer. Microcell-mediated transfer of chromosome 18 in the ovarian cancer cell line TOV21G induced in vitro and in vivo neoplastic suppression. Gene expression microarray...

  14. 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...

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

    Science.gov (United States)

    Earp, Madalene A; Kelemen, Linda E; Magliocco, Anthony M; Swenerton, Kenneth D; Chenevix-Trench, Georgia; Lu, Yi; Hein, Alexander; Ekici, Arif B; Beckmann, Matthias W; Fasching, Peter A; Lambrechts, Diether; Despierre, Evelyn; Vergote, Ignace; Lambrechts, Sandrina; Doherty, Jennifer A; Rossing, Mary Anne; Chang-Claude, Jenny; Rudolph, Anja; Friel, Grace; Moysich, Kirsten B; Odunsi, Kunle; Sucheston-Campbell, Lara; Lurie, Galina; Goodman, Marc T; Carney, Michael E; Thompson, Pamela J; Runnebaum, Ingo B; Dürst, Matthias; Hillemanns, Peter; Dörk, Thilo; Antonenkova, Natalia; Bogdanova, Natalia; Leminen, Arto; Nevanlinna, Heli; Pelttari, Liisa M; Butzow, Ralf; Bunker, Clareann H; Modugno, Francesmary; Edwards, Robert P; Ness, Roberta B; du Bois, Andreas; Heitz, Florian; Schwaab, Ira; Harter, Philipp; Karlan, Beth Y; Walsh, Christine; Lester, Jenny; Jensen, Allan; Kjær, Susanne K; Høgdall, Claus K; Høgdall, Estrid; Lundvall, Lene; Sellers, Thomas A; Fridley, Brooke L; Goode, Ellen L; Cunningham, Julie M; Vierkant, Robert A; Giles, Graham G; Baglietto, Laura; Severi, Gianluca; Southey, Melissa C; Liang, Dong; Wu, Xifeng; Lu, Karen; Hildebrandt, Michelle A T; Levine, Douglas A; Bisogna, Maria; Schildkraut, Joellen M; Iversen, Edwin S; Weber, Rachel Palmieri; Berchuck, Andrew; Cramer, Daniel W; Terry, Kathryn L; Poole, Elizabeth M; Tworoger, Shelley S; Bandera, Elisa V; Chandran, Urmila; Orlow, Irene; Olson, Sara H; Wik, Elisabeth; Salvesen, Helga B; Bjorge, Line; Halle, Mari K; van Altena, Anne M; Aben, Katja K H; Kiemeney, Lambertus A; Massuger, Leon F A G; Pejovic, Tanja; Bean, Yukie T; Cybulski, Cezary; Gronwald, Jacek; Lubinski, Jan; Wentzensen, Nicolas; Brinton, Louise A; Lissowska, Jolanta; Garcia-Closas, Montserrat; Dicks, Ed; Dennis, Joe; Easton, Douglas F; Song, Honglin; Tyrer, Jonathan P; Pharoah, Paul D P; Eccles, Diana; Campbell, Ian G; Whittemore, Alice S; McGuire, Valerie; Sieh, Weiva; Rothstein, Joseph H; Flanagan, James M; Paul, James; Brown, Robert; Phelan, Catherine M; Risch, Harvey A; McLaughlin, John R; Narod, Steven A; Ziogas, Argyrios; Anton-Culver, Hoda; Gentry-Maharaj, Aleksandra; Menon, Usha; Gayther, Simon A; Ramus, Susan J; Wu, Anna H; Pearce, Celeste L; Pike, Malcolm C; Dansonka-Mieszkowska, Agnieszka; Rzepecka, Iwona K; Szafron, Lukasz M; Kupryjanczyk, Jolanta; Cook, Linda S; Le, Nhu D; Brooks-Wilson, Angela

    2014-05-01

    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 pooling genomic DNA from 545 cases and 398 controls of European descent, and testing for allelic associations. We evaluated for replication 188 variants from the GWAS [56 variants for mucinous, 55 for endometrioid and clear cell, 53 for low-malignant potential (LMP) serous, and 24 for invasive serous EOC], selected using pre-defined criteria. Genotypes from 13,188 cases and 23,164 controls of European descent were used to perform unconditional logistic regression under the log-additive genetic model; odds ratios (OR) and 95 % confidence intervals are reported. Nine variants tagging six loci were associated with subtype-specific EOC risk at P < 0.05, and had an OR that agreed in direction of effect with the GWAS results. Several of these variants are in or near genes with a biological rationale for conferring EOC risk, including ZFP36L1 and RAD51B for mucinous EOC (rs17106154, OR = 1.17, P = 0.029, n = 1,483 cases), GRB10 for endometrioid and clear cell EOC (rs2190503, P = 0.014, n = 2,903 cases), and C22orf26/BPIL2 for LMP serous EOC (rs9609538, OR = 0.86, P = 0.0043, n = 892 cases). In analyses that included the 75 GWAS samples, the association between rs9609538 (OR = 0.84, P = 0.0007) and LMP serous EOC risk remained statistically significant at P < 0.0012 adjusted for multiple testing. Replication in additional samples will be important to verify these results for the less-common EOC subtypes. PMID:24190013

  16. 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

  17. 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.

  18. Diagnosis and management of peritoneal metastases from ovarian cancer.

    Science.gov (United States)

    Halkia, Evgenia; Spiliotis, John; Sugarbaker, Paul

    2012-01-01

    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. PMID:22888339

  19. 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.

  20. 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

  1. 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 ...

  2. Microcell-Mediated Chromosome Transfer Identifies EPB41L3 as a Functional Suppressor of Epithelial Ovarian Cancers

    OpenAIRE

    Dimitra Dafou; Barbara Grun; John Sinclair; Kate Lawrenson; Benjamin, Elizabeth C; Estrid Hogdall; Susanne Kruger-Kjaer; Lise Christensen; Sowter, Heidi M.; Ahmed Al-Attar; Richard Edmondson; Stephen Darby; Andrew Berchuck; Laird, Peter W; C. Leigh Pearce

    2010-01-01

    We used a functional complementation approach to identify tumor-suppressor genes and putative therapeutic targets for ovarian cancer. Microcell-mediated transfer of chromosome 18 in the ovarian cancer cell line TOV21 G induced in vitro and in vivo neoplastic suppression. Gene expression microarray profiling in TOV21 +19 hybrids identified 14 candidate genes on chromosome 18 that were significantly overexpressed and therefore associated with neoplastic suppression. Further analysis of messenge...

  3. 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 ca...

  4. Prostasin和Claudin -3在卵巢上皮性癌中的表达及意义%Expressions and significances of Prostasin and Claudin - 3 in epithelial ovarian cancer

    Institute of Scientific and Technical Information of China (English)

    尹相力; 孔红霞

    2011-01-01

    目的:探讨前列腺蛋白( Prostasin)和紧密连接蛋白3(Claudin -3)在卵巢上皮性癌中的表达及临床意义.方法:采用免疫组化SP法检测Prostasin和Claudin -3在50例卵巢上皮性癌、20例卵巢交界性肿瘤、20例卵巢良性肿瘤、20例正常卵巢组织中的表达情况.结果:Prostasin和Claudin -3在卵巢上皮性癌中的表达均明显高于其他三组(P<0.05),二者在卵巢上皮性癌中的表达与组织病理分级、临床分期有关(P<0.05),与组织学分型无关(P>0.05);Prostasin和Claudin -3在卵巢上皮性癌中的表达呈正相关(r=0.386,P<0.05).结论:Prostasin和Claudin-3的表达升高与卵巢上皮性癌的发生、发展密切相关,Prostasin和Claudin -3有可能成为治疗卵巢癌的新靶点.%Objective; To explore the expressions and significances of Prostasin and Claudin - 3 in ovarian epithelial cancer. Methods; Immunohistochemical SP method was used to detect the expression levels of Prostasin and Claudin -3 in 50 cases with o-varian epithelial cancer, 20 cases with borderline ovarian tumor, 20 cases with benign ovarian tumor and 20 cases with normal ovarian tissues. Results: The expression levels of Prostasin and Claudin -3 in ovarian epithelial cancer were significantly higher than those in the other three groups (P 0.05); there was positive correlation between Prostasin expression and Claudin - 3 expression in ovarian epithelial cancer (y = 0.386, P < 0.05 ) . Conclusion; The high expressions of Prostasin and Claudin - 3 are correlated with the occurrence and development of ovarian epithelial cancer. Prostasin and Claudin - 3 may become new targets for treatment of ovarian cancer.

  5. 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.

  6. Advanced small-cell ovarian carcinoma, hypercalcemic type: a challenging therapeutic entity

    Directory of Open Access Journals (Sweden)

    Rafael Caparica Bitton

    2014-09-01

    Full Text Available Small-cell ovarian carcinoma (SCOC is a rare and aggressive neoplasia, predominantly affecting young women who are frequently first diagnosed with advanced stage disease. Platinum-based chemotherapy (ChT can provide high response rates and rapidly ameliorate symptoms in this scenario. However, progression after chemotherapy usually occurs quickly, leading to high mortality rates. In addition, ChT complications, such as tumor lysis syndrome (TLS can also occur, jeopardizing the patient’s outcome. We present a case of metastatic SCOC in a 47-year-old patient who achieved tumor response after platinum-based chemotherapy and developed TLS, from which she recovered with supportive treatment. After the second ChT cycle, she developed febrile neutropenia and died 8 weeks after the diagnosis of SCOC. Although SCOC is a chemo-sensitive tumor, short-lived responses and frequent chemotherapy complications lead to a dismal prognosis.

  7. Metformin Hydrochloride and Combination Chemotherapy in Treating Patients With Stage III-IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

    Science.gov (United States)

    2016-05-18

    Brenner Tumor; Malignant Ascites; Malignant Pleural Effusion; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Epithelial Carcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Undifferentiated Adenocarcinoma; Recurrent Fallopian Tube Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Primary Peritoneal Cavity Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIA Primary Peritoneal Cavity Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIB Primary Peritoneal Cavity Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IIIC Primary Peritoneal Cavity Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Primary Peritoneal Cavity Cancer

  8. 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.

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

    DEFF Research Database (Denmark)

    Bois, Andreas du; 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......BACKGROUND: Angiogenesis is a target in the treatment of ovarian cancer. Nintedanib, an oral triple angiokinase inhibitor of VEGF receptor, platelet-derived growth factor receptor, and fibroblast growth factor receptor, has shown activity in phase 2 trials in this setting. We investigated......-IV ovarian cancer and upfront debulking surgery were stratified by postoperative resection status, FIGO stage, and planned carboplatin dose. Patients were randomly assigned (2:1) via an interactive voice or web-based response system to receive six cycles of carboplatin (AUC 5 mg/mL per min or 6 mg/mL per min...

  10. 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...

  11. Pathobiology of ovarian carcinomas

    OpenAIRE

    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 bas...

  12. Synthesis and pre-clinical evaluation of an (18)F-labeled single-chain antibody fragment for PET imaging of epithelial ovarian cancer.

    Science.gov (United States)

    Sharma, Sai Kiran; Wuest, Melinda; Way, Jenilee D; Bouvet, Vincent R; Wang, Monica; Wuest, Frank R

    2016-01-01

    Anti-CA125 antibodies have been used in immunoassays to quantify levels of shed antigen in the serum of patients who are under surveillance for epithelial ovarian cancer (EOC). However, there is currently no molecular imaging probe in the clinic for the assessment of CA125 expression in vivo. The present study describes the development of an (18)F-labeled single-chain variable fragment (scFv) for PET imaging of CA125 in preclinical EOC models. Anti-CA125 scFv was derived from MAb-B43.13 by recombinant expression of the fragment in E.coli. Fragment scFv-B43.13 was purified via immobilized metal affinity chromatography and characterized for antigen binding via immuno-staining and flow cytometry. Prosthetic group N-succinimidyl 4-[(18)F]fluorobenzoate ([(18)F]SFB) was used for radiolabeling of scFv-B43.13. Preclinical ovarian cancer models were developed based on ovarian cancer cell lines OVCAR3 (CA125-positive) and SKOV3 (CA125-negative) in NIH-III mice. The radiopharmacological profile of (18)F-labeled scFv-B43.13 ([(18)F]FBz-scFv-B43.13) was studied with PET. [(18)F]FBz-scFv-B43.13 was prepared in radiochemical yields of 3.7 ± 1.8% (n = 5) at an effective specific activity of 3.88 ± 0.76 GBq/µmol (n = 5). The radiotracer demonstrated selective uptake in CA125-positive OVCAR3 cells and virtually no uptake in CA125-negative SKOV3 cells. Standardized uptake values (SUV) of radioactivity uptake in OVCAR3 tumors was 0.5 (n = 3) and 0.3 (n = 2) in SKOV3 tumors after 60 min post injection (p.i.). PMID:27508105

  13. Synthesis and pre-clinical evaluation of an 18F-labeled single-chain antibody fragment for PET imaging of epithelial ovarian cancer

    Science.gov (United States)

    Sharma, Sai Kiran; Wuest, Melinda; Way, Jenilee D; Bouvet, Vincent R; Wang, Monica; Wuest, Frank R

    2016-01-01

    Anti-CA125 antibodies have been used in immunoassays to quantify levels of shed antigen in the serum of patients who are under surveillance for epithelial ovarian cancer (EOC). However, there is currently no molecular imaging probe in the clinic for the assessment of CA125 expression in vivo. The present study describes the development of an 18F-labeled single-chain variable fragment (scFv) for PET imaging of CA125 in preclinical EOC models. Anti-CA125 scFv was derived from MAb-B43.13 by recombinant expression of the fragment in E.coli. Fragment scFv-B43.13 was purified via immobilized metal affinity chromatography and characterized for antigen binding via immuno-staining and flow cytometry. Prosthetic group N-succinimidyl 4-[18F]fluorobenzoate ([18F]SFB) was used for radiolabeling of scFv-B43.13. Preclinical ovarian cancer models were developed based on ovarian cancer cell lines OVCAR3 (CA125-positive) and SKOV3 (CA125-negative) in NIH-III mice. The radiopharmacological profile of 18F-labeled scFv-B43.13 ([18F]FBz-scFv-B43.13) was studied with PET. [18F]FBz-scFv-B43.13 was prepared in radiochemical yields of 3.7 ± 1.8% (n = 5) at an effective specific activity of 3.88 ± 0.76 GBq/µmol (n = 5). The radiotracer demonstrated selective uptake in CA125-positive OVCAR3 cells and virtually no uptake in CA125-negative SKOV3 cells. Standardized uptake values (SUV) of radioactivity uptake in OVCAR3 tumors was 0.5 (n = 3) and 0.3 (n = 2) in SKOV3 tumors after 60 min post injection (p.i.). PMID:27508105

  14. Avian SERPINB12 expression in the avian oviduct is regulated by estrogen and up-regulated in epithelial cell-derived ovarian carcinomas of laying hens.

    Directory of Open Access Journals (Sweden)

    Gahee Jo

    Full Text Available Serine protease inhibitors (SERPINs are involved in a variety of biological processes such as blood clotting, angiogenesis, immune system, and embryogenesis. Although, of these, SERPINB12 is identified as the latest member of clade B in humans, little is known of it in chickens. Thus, in this study, we investigated SERPINB12 expression profiles in various tissues of chickens and focused on effects of steroid hormone regulation of its expression. In the chicken oviduct, SERPINB12 mRNA and protein are abundant in the luminal (LE and glandular (GE epithelia of the magnum in response to endogenous or exogenous estrogen. Furthermore, SERPINB12 mRNA and protein increase significantly in GE of cancerous ovaries of laying hens with epithelia-derived ovarian cancer. Collectively, these results indicate that SERPINB12 is a novel estrogen-stimulated gene that is up-regulated by estrogen in epithelial cells of the chicken oviduct and that it is a potential biomarker for early detection of ovarian carcinomas in laying hens and women.

  15. Avian SERPINB12 expression in the avian oviduct is regulated by estrogen and up-regulated in epithelial cell-derived ovarian carcinomas of laying hens.

    Science.gov (United States)

    Jo, Gahee; Lim, Whasun; Bae, Seung-Min; Bazer, Fuller W; Song, Gwonhwa

    2014-01-01

    Serine protease inhibitors (SERPINs) are involved in a variety of biological processes such as blood clotting, angiogenesis, immune system, and embryogenesis. Although, of these, SERPINB12 is identified as the latest member of clade B in humans, little is known of it in chickens. Thus, in this study, we investigated SERPINB12 expression profiles in various tissues of chickens and focused on effects of steroid hormone regulation of its expression. In the chicken oviduct, SERPINB12 mRNA and protein are abundant in the luminal (LE) and glandular (GE) epithelia of the magnum in response to endogenous or exogenous estrogen. Furthermore, SERPINB12 mRNA and protein increase significantly in GE of cancerous ovaries of laying hens with epithelia-derived ovarian cancer. Collectively, these results indicate that SERPINB12 is a novel estrogen-stimulated gene that is up-regulated by estrogen in epithelial cells of the chicken oviduct and that it is a potential biomarker for early detection of ovarian carcinomas in laying hens and women. PMID:25020046

  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

    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 4,3...

  17. 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 a...

  18. 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).

  19. Changes in Brain Function in Patients With Stage I, Stage II, Stage III, or Stage IV Ovarian, Primary Peritoneal, or Fallopian Tube Cancer Who Are Receiving Chemotherapy

    Science.gov (United States)

    2016-02-09

    Cognitive Side Effects of Cancer Therapy; Malignant Ovarian Epithelial Tumor; Malignant Ovarian Mixed Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Carcinosarcoma; Ovarian Choriocarcinoma; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Dysgerminoma; Ovarian Embryonal Carcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Germ Cell Tumor; Ovarian Mucinous Cystadenocarcinoma; Ovarian Polyembryoma; Ovarian Sarcoma; Ovarian Serous Cystadenocarcinoma; Ovarian Teratoma; Ovarian Yolk Sac Tumor; Stage I Ovarian Cancer; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Cancer; Stage IA Ovarian Germ Cell Tumor; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Cancer; Stage IB Ovarian Germ Cell Tumor; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Cancer; Stage IC Ovarian Germ Cell Tumor; Stage II Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIA Ovarian Germ Cell Tumor; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIB Ovarian Germ Cell Tumor; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIC Ovarian Germ Cell Tumor; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Primary Peritoneal Cancer; Undifferentiated Ovarian Carcinoma

  20. Livin、Smac和Ki67在上皮性卵巢癌中的表达及意义%Expressions and significances of Livin,Smac and Ki67 in epithelial ovarian carcinoma

    Institute of Scientific and Technical Information of China (English)

    刘文博; 孔红霞

    2011-01-01

    目的:探讨凋亡抑制蛋白Livin、凋亡相关因子Smac和细胞增殖核抗原Ki67在上皮性卵巢癌的表达及临床意义,并分析三者的相关性.方法:利用免疫组化SP法检测50例上皮性卵巢癌、20例交界性卵巢肿瘤、20例良性卵巢肿瘤和20例正常卵巢组织中三者的表达情况.结果:Livin与Ki67在卵巢癌中的表达明显高于其他3组(P<0.01),在卵巢组织中的表达与组织病理学分级和有无淋巴结转移呈正相关(P<0,05),与组织学类型、分期无关.Smac在卵巢癌中的表达明显低于其他3组(P<0.01),在卵巢组织中的表达与组织病理学分级和有无淋巴结转移呈负相关(p<0.05),与组织学类型、分期无关.结论:Livin、Smac和Ki67在上皮性卵巢癌的发生、分化、进展过程中起重要作用;Livin、Smac和Ki67有望成为治疗卵巢癌的新靶点.%Objective: To explore the expressions and significances of inhibitor of apoptosis protein - Livin, apoptosis related factor -Smac and proliferating cell nuclear antigen - Ki67 in epithelial ovarian carcinoma, and analyze their correlation. Methods: Immunohistochemical SP method was used to detect the expression levels of Livin, .Smac and Ki67 in 50 cases with epithelial ovarian cancer, 20 cases with borderline ovarian tumor, 20 cases with benign ovarian tumor and 20 cases with normal ovarian tissues. Results: The expression levels of Livin and Ki67 in epithelial ovarian cancer group were significantly higher than those in the other three groups ( P < 0. 01 ) . There was positive correlation between expression levels of Livin and Ki67 in ovarian tissues and histopathological grades, lymph node metastasis ( P <0. 05 ), but they were not related to histological types and stages. The expression level of Smac in epithelial ovarian cancer group was significantly lower than those in the other three groups ( P < 0. 01 ) . There was negative correlation between expression level of Smac in ovarian

  1. 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.

  2. Effect of Procyanidin-rich Extract from Natural Cocoa Powder on Cellular Viability, Cell Cycle Progression, and Chemoresistance in Human Epithelial Ovarian Carcinoma Cell Lines

    Science.gov (United States)

    Taparia, Shruti; Khanna, Aparna

    2016-01-01

    Background: Over the last 400 years, cocoa and chocolate have been described as having potential medicinal value, being consumed as a beverage or eaten as food. Concentration–dependant, antiproliferation, and cytotoxic effects of some of their polyphenolic constituents have been demonstrated against various cancers. Such an effect remains to be demonstrated in ovarian cancer Objective: To investigate the effect of cocoa procyanidins against ovarian cancer in vitro using OAW42 and OVCAR3 cell lines. Materials and Methods: Cocoa procyanidins were extracted and enriched from non alkalized cocoa powder. The polyphenolic content and antioxidant activity were determined. Effect on cell viability was determined after the treatment with ≤1000 μg/mL cocoa procyanidin-rich extract on OAW42 and OVCAR3 and normal human dermal fibroblasts. Similarly, chemosensitization effect was determined by pretreating cancer cell lines with extract followed by doxorubicin hydrochloride treatment. The effect of treatment on cell cycle and P-glycoprotein (P-gp) expression was determined using flow cytometry. Results: The cocoa extract showed high polyphenolic content and antioxidant activity. Treatment with extract caused cytotoxicity and chemosensitization in OAW42 and OVCAR3 cell lines. Normal dermal fibroblasts showed an increase in cell viability post treatment with extract. Treatment with extract affected the cell cycle and an increasing percentage of cells in hypodiploid sub-G1/G0 phase was observed. Treatment of OVCAR3 with the extract caused reduction of P-gp expression. Conclusion: Cocoa procyanidins were found to be selectively cytotoxic against epithelial ovarian cancer, interfered with the normal cell cycle and sensitized cells to subsequent chemotherapeutic treatment. Chemosensitization was found to be associated with P-gp reduction in OVCAR3 cells. SUMMARY Among the naturally occurring flavonoids, procyanidins have been shown to be effective against cancersNon alkalized

  3. Outcome of Epithelial Ovarian Cancer Time for Strategy Trials to Resolve the Problem of Optimal Timing of Surgery

    OpenAIRE

    Van de Putte, Gregg; Oben, Jolien; Prenen, Leen; Schobbens, Jean Christophe; Vlasselaer, Jos; Van Holsbeke, Caroline; Debrock, Guy; Van Eycken, Peter; DE JONGE, Eric

    2015-01-01

    Introduction The standard treatment of ovarian cancer is the combination of debulking surgery and chemotherapy. There is an ongoing discussion on which treatment is best: primary debulking surgery (PDS) or neoadjuvant chemotherapy with interval debulking (NACT-IDS). Even a large randomized trial has not settled this issue. We examined whether comparing a specified treatment protocol would not be a more logical approach to answer this type of discussions. Methods A retrospective study of 142 c...

  4. 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...

  5. THE ABERRANT PROMOTER HYPERMETHYLATION PATTERN OF THE ANTI - ANGIOGENIC TSP1 GENE IN EPITHELIAL OVARIAN CARCINOMA: AN INDIAN STUDY

    Directory of Open Access Journals (Sweden)

    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.

  6. 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

  7. Neoadjuvant chemotherapy for advanced ovarian cancer: literature data and in vitro studies

    Directory of Open Access Journals (Sweden)

    S. A. Kuznetsov

    2015-01-01

    Full Text Available This paper analyzes large amounts of literature data on studies of the efficiency of neoadjuvant chemotherapy (NCT for advanced ovarian cancer (OC, which is performed prior to standard surgery. Clinical trials have demonstrated that a NCT regimen followed by cytoreductive surgery is less effective than primary cytoreductive one; however, evidence for the benefit of NCT is lacking so far. The authors conducted investigations using the intraoperative material obtained from 17 patients with T3a–cNxM0 OC, who were divided for a comparative examination into 2 groups. Group 1 included OC patents who received NCT; Group 2 comprised OC patients who did not. The tumor cells obtained from the intraoperative material of both groups were able to generate a well-proliferating culture in in vitro experiments. The cultured OC cells were characterized, by analyzing cytological specimens and the functional activity of these cells. It was ascertained that 35 % of the cultured tumor cells from OC retained their resistance to the cytotoxic action of effector cells (autologous lymphocytes at a target cell/effector cell ratio of 1:5. Thus, both the literature and the experiment provide no unambiguous evidence supporting the fact that NCT before cytoreductive surgery is a better approach than primary surgical treatment. The optimal regimen of NCT, which would be able to enhance its efficiency, remains important. 

  8. 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.

  9. Oxidatively Modified Proteins in the Serous Subtype of Ovarian Carcinoma

    Directory of Open Access Journals (Sweden)

    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.

  10. 卵巢交界性上皮性肿瘤36例临床分析%A clinical analysis of 36 ovarian borderline epithelial tumors

    Institute of Scientific and Technical Information of China (English)

    安云婷; 郑子雯

    2009-01-01

    Objective:To explore the clinical features and management of ovarian borderline epithelial tumors(BOT).Methods:Thirty six cases with ovarian borderline epithelial tumor were analyzed retrospectively.Results:The average age of the patients was 37.9 years.Pathological type included 17 cases(47.2%) of mucous tumor,16 cases(44.5%) of serious tumor,2 cases(5.5%) of endometrioid tumor and 1 case(2.8%) of clear cell tumor.Thirty-four patients accepted surgical treatment,28 cases(82.4%) were in surgical-pathologic stage Ⅰ,5 cases(14.7%) of serious tumor were in stage Ⅲ,1case(2.9%) relapsed(stage Ⅰ).twenty one cases include all cases of stage Ⅱ and Ⅲ received postoperative chemotherapy.Conclusion:Ovarian borderline epithelial tumor appears to have a favorable prognosis,surgery is the proved only effective treatment till now.Conservative surgery is proper treatment for young women with borderline ovary tumors in stage Ⅰ,but careful follow up will be required to detect tumor recurrence.A high proportion of borderline tumors of the ovary,particularly of the serous type,were associated with elevated CA125 level.%目的:探讨卵巢交界性上皮肿瘤的临床特征和治疗方法.方法:收集江西省妇幼保健院2003年至2007年36例卵巢交界性上皮性肿瘤患者临床资料,运用SPSS 11.5软件进行临床和病理统计分析.结果:发病年龄平均37.9岁,粘液性17例(47.2% ),浆液性16例(44.5% ),子宫内膜样2例(5.5%),透明细胞1例(2.8%).34例患者行手术治疗,其中Ⅰ期28例(82.4%),Ⅲ期5例(14.7%)均为浆液性,治疗后1例(2.9% ,Ⅰ期)浆液性复发.治疗方法以手术为主,21例于术后补充TP或PAC方案化疗,Ⅱ期与Ⅲ期患者均辅以化疗.结论:卵巢交界性上皮性肿瘤预后良好,手术是其有效的治疗手段,对临床Ⅰa期,尤其需保留生育功能者,保守性手术较安全有效.浆液性外生性乳头状交界瘤多伴有腹膜种植,应行分期手术.CA125是监测卵巢非黏液性

  11. 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.

  12. 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

  13. 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

  14. The tumour suppressor SOX11 is associated with improved survival among high grade epithelial ovarian cancers and is regulated by reversible promoter methylation

    International Nuclear Information System (INIS)

    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. 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. 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. 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

  15. Advanced Ovarian Dysgerminoma Infiltrating Both Ovaries and Uterus in a 7-Year-Old Girl

    OpenAIRE

    Nexhmi Hyseni; Sadik Llullaku; Hysni Jashari; Kaltrina Zahiti; Fjolla Hyseni; Fisnik Kurshumliu; Lumturije Luci; Fehim Muqolli; Antigona Hasani

    2014-01-01

    Introduction. Ovarian dysgerminoma is a rare malignant ovarian germ cell tumor with its peak incidence in young women. Abdominal pain, abdominal distention, and the presence of a palpable mass are common symptoms at presentation. Depending on the FIGO stage at presentation the prognosis of dysgerminomas after surgical treatment, adjuvant chemotherapy, and radiotherapy is promising. Case Presentation. A 7-year-old girl was presented at our clinic with abdominal pain in all abdominal quadrants....

  16. 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.

  17. Gene Set-Based Functionome Analysis of Pathogenesis in Epithelial Ovarian Serous Carcinoma and the Molecular Features in Different FIGO Stages.

    Science.gov (United States)

    Chang, Chia-Ming; Chuang, Chi-Mu; Wang, Mong-Lien; Yang, Ming-Jie; Chang, Cheng-Chang; Yen, Ming-Shyen; Chiou, Shih-Hwa

    2016-01-01

    Serous carcinoma (SC) is the most common subtype of epithelial ovarian carcinoma and is divided into four stages by the Federation of Gynecologists and Obstetrics (FIGO) staging system. Currently, the molecular functions and biological processes of SC at different FIGO stages have not been quantified. Here, we conducted a whole-genome integrative analysis to investigate the functions of SC at different stages. The function, as defined by the GO term or canonical pathway gene set, was quantified by measuring the changes in the gene expressional order between cancerous and normal control states. The quantified function, i.e., the gene set regularity (GSR) index, was utilized to investigate the pathogenesis and functional regulation of SC at different FIGO stages. We showed that the informativeness of the GSR indices was sufficient for accurate pattern recognition and classification for machine learning. The function regularity presented by the GSR indices showed stepwise deterioration during SC progression from FIGO stage I to stage IV. The pathogenesis of SC was centered on cell cycle deregulation and accompanied with multiple functional aberrations as well as their interactions. PMID:27275818

  18. 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.

  19. 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...

  20. 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

  1. Effect of taurine on advanced glycation end products-induced hypertrophy in renal tubular epithelial cells

    International Nuclear Information System (INIS)

    Mounting evidence indicates that advanced glycation end products (AGE) play a major role in the development of diabetic nephropathy (DN). Taurine is a well documented antioxidant agent. To explore whether taurine was linked to altered AGE-mediated renal tubulointerstitial fibrosis in DN, we examined the molecular mechanisms of taurine responsible for inhibition of AGE-induced hypertrophy in renal tubular epithelial cells. We found that AGE (but not non-glycated BSA) caused inhibition of cellular mitogenesis rather than cell death by either necrosis or apoptosis. There were no changes in caspase 3 activity, bcl-2 protein expression, and mitochondrial cytochrome c release in BSA, AGE, or the antioxidant taurine treatments in these cells. AGE-induced the Raf-1/extracellular signal-regulated kinase (ERK) activation was markedly blocked by taurine. Furthermore, taurine, the Raf-1 kinase inhibitor GW5074, and the ERK kinase inhibitor PD98059 may have the ability to induce cellular proliferation and cell cycle progression from AGE-treated cells. The ability of taurine, GW5074, or PD98059 to inhibit AGE-induced hypertrophy was verified by the observation that it significantly decreased cell size, cellular hypertrophy index, and protein levels of RAGE, p27Kip1, collagen IV, and fibronectin. The results obtained in this study suggest that taurine may serve as the potential anti-fibrotic activity in DN through mechanism dependent of its Raf-1/ERK inactivation in AGE-induced hypertrophy in renal tubular epithelial cells

  2. The roles of miRNAs in the pathogenesis of epithelial ovarian cancer and its clinical significance%微RNA在卵巢上皮性癌发生发展中作用及其临床意义

    Institute of Scientific and Technical Information of China (English)

    程妮; 朱耀魁; 张磊; 岑颖洲

    2012-01-01

    Previous studies show that miRNAs have participated in numerous pathophysiological processes such as embryonic development, injury repair, diabetes and heart desease. Particularly, miRNAs play an extremely important role in the pathogenesis of malignant tumor and possess numerous potential clinical significance. The miRNA expression profile in the tissue sample and cell lines of epithelial ovarian cancer(EOC) has been determined and the mechanism by which miRNAs act in the pathogenesis of EOC has been preliminarily investigated. Those other latest advances in term of miRNAs and early diagnosis and chemotherapy resistance and prognosis prediction of EOC were also reviewed in this paper.%研究表明,miRNA参与了胚胎发育、损伤修复、糖尿病、心脏病等许多重要生理病理过程,特别是在恶性肿瘤的发生发展中发挥了重要作用,并具有潜在的临床意义.本文比较详细地叙述了有关miRNA 的重要基础研究成果,并就miRNA在卵巢癌组织及细胞中的表达、miRNA在卵巢癌发生发展中的作用、miRNA与卵巢癌早期诊断、化疗耐药及预后判断等方面的最新研究成果进行了综述.

  3. 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

  4. 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

  5. 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.

  6. Intensity-Modulated Whole Abdominal Radiotherapy After Surgery and Carboplatin/Taxane Chemotherapy for Advanced Ovarian Cancer: Phase I Study

    International Nuclear Information System (INIS)

    Purpose: To assess the feasibility and toxicity of consolidative intensity-modulated whole abdominal radiotherapy (WAR) after surgery and chemotherapy in high-risk patients with advanced ovarian cancer. Methods and Materials: Ten patients with optimally debulked ovarian cancer International Federation of Gynecology and Obstetrics Stage IIIc were treated in a Phase I study with intensity-modulated WAR up to a total dose of 30 Gy in 1.5-Gy fractions as consolidation therapy after adjuvant carboplatin/taxane chemotherapy. Treatment was delivered using intensity-modulated radiotherapy in a step-and-shoot technique (n = 3) or a helical tomotherapy technique (n = 7). The planning target volume included the entire peritoneal cavity and the pelvic and para-aortal node regions. Organs at risk were kidneys, liver, heart, vertebral bodies, and pelvic bones. Results: Intensity-modulated WAR resulted in an excellent coverage of the planning target volume and an effective sparing of the organs at risk. The treatment was well tolerated, and no severe Grade 4 acute side effects occurred. Common Toxicity Criteria Grade III toxicities were as follows: diarrhea (n = 1), thrombocytopenia (n = 1), and leukopenia (n = 3). Radiotherapy could be completed by all the patients without any toxicity-related interruption. Median follow-up was 23 months, and 4 patients had tumor recurrence (intraperitoneal progression, n = 3; hepatic metastasis, n = 1). Small bowel obstruction caused by adhesions occurred in 3 patients. Conclusions: The results of this Phase I study showed for the first time, to our knowledge, the clinical feasibility of intensity-modulated whole abdominal radiotherapy, which could offer a new therapeutic option for consolidation treatment of advanced ovarian carcinoma after adjuvant chemotherapy in selected subgroups of patients. We initiated a Phase II study to further evaluate the toxicity of this intensive multimodal treatment.

  7. 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

  8. 高压氧联合化疗对卵巢上皮性癌疗效研究%Study of therapeutic efficacy of hyperbaric oxygen combined with chemotherapy on epithelial ovarian cancer

    Institute of Scientific and Technical Information of China (English)

    郝俊秀; 高善霞

    2010-01-01

    .4% (13/28), (18.0 ± 0.6) months, 17.9% (5/28)] (P <0.05), progression-free survival and overall survival time in HBO group were longer than those in PC group (P <0.05) and adverse reactions rate in HBO group was lower than that in PC group (P <0.05).Conclusions The hyperbaric oxygen combined with PC programs are better than PC programs in advanced epithelial ovarian cancer chemotherapy response rate, progression-free survival time and 3-year survival rates in ovarian cancer adjuvant chemotherapy. HBO can significantly reduce the PC's hematological toxicity and toxicity of the digestive system.

  9. 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...

  10. Animal models of ovarian cancer

    OpenAIRE

    Shaw Tanya J; Vanderhyden Barbara C; Ethier Jean-François

    2003-01-01

    Abstract Ovarian cancer is the most lethal of all of the gynecological cancers and can arise from any cell type of the ovary, including germ cells, granulosa or stromal cells. However, the majority of ovarian cancers arise from the surface epithelium, a single layer of cells that covers the surface of the ovary. The lack of a reliable and specific method for the early detection of epithelial ovarian cancer results in diagnosis occurring most commonly at late clinical stages, when treatment is...

  11. 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.

  12. 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

  13. The influence of CA 125 and CEA levels on the results of 18F-deoxyglucose positron emission tomography in suspected recurrence of epithelial ovarian cancer

    International Nuclear Information System (INIS)

    Background and Purpose: The follow-up of epithelial ovarian cancer (OCA) consists of clinical investigation, sonography, and tumor markers (TMs), especially CA 125. If tumor recurrence is suspected, other imaging modalities including positron emission tomography (PET) with 18F-deoxyglucose (FDG) are often used. While there is still no consensus about the method of choice and the timing of its application, this study aims to find a TM threshold at which a PET would be appropriate. Material and Methods: A total of 90 PET studies and the associated CA 125 values (normal value <35 U/ml) were available in 71 patients during the follow-up afte primary therapy for OCA. In 48 studies a CEA value (normal value <3 ng/ml) was also available. The results of PET imaging were related to the level of TM increase. Results: In 23/90 studies the PET scan was normal. These patients had a median CA 125 of 13.3 U/ml (range 4.2-168 U/ml). In 67/90 studies the PET indicated a potential recurrence of OCA and the median CA 125 was 166.7 U/ml (range 13.3-4,060 U/ml). The TM levels were significantly different (p<0.001, U-test). With one exception, there were no normal PET scans above CA 125 levels of 30 U/ml; between 20 and 30 U/ml PET was positive in 4/7 studies. Conclusion: In suspected recurrence of OCA, if imaging modalities are to be used, an FDG PET may be considered. Since the costs of this investigation are high, it should be restricted to clinical situations where it is likely to be most effective. In this study a PET indication is worthwhile at CA 125 levels of approximately 30 U/ml. (orig.)

  14. 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

    Directory of Open Access Journals (Sweden)

    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.

  15. Aquaporin 3 is regulated by estrogen in the chicken oviduct and is involved in progression of epithelial cell-derived ovarian carcinomas.

    Science.gov (United States)

    Yang, C; Lim, W; Bae, H; Song, G

    2016-04-01

    Aquaporins (AQPs) are membrane proteins that passively deliver water across the plasma membrane to play an important role in maintaining cell shape. Members of the AQP family are distributed in most of the tissues in the human body and perform a variety of functions based on the water homeostasis suitable for each organ. However, there is little known about the expression and regulation of AQP family members in chickens. Therefore, we determined the expression of AQPs in various tissues of chickens. Among 13 isotypes, AQP3 was highly expressed in the chicken oviduct. Expression of AQP3 messenger RNA (mRNA) increased in the magnum (P glandular and luminal epithelia of the magnum and isthmus of oviducts of diethylstilbestrol-treated chicks. In addition, the pattern of expression of AQP3 changed in an estrogen-dependent manner during the molting period. During the regenerative period of the oviduct after molting, expression of AQP3 mRNA increased coordinately with increasing concentrations of estradiol (P < 0.001), whereas expression of AQP3 mRNA decreased as concentrations of estradiol in plasma decreased in response to induced molting (P < 0.001). Also, expression of the AQP3 increased (P < 0.001) in cancerous ovaries of laying hens. In conclusion, AQP3 does not simply function to transport water into and out of cells but also appears to be closely involved in development of the chicken oviduct, which is regulated by estrogens. Furthermore, our results suggest AQP3 as a new diagnostic for early detection and treatment of epithelial cell-derived ovarian carcinomas. PMID:26808975

  16. Weekly Paclitaxel Versus Three-Weekly Paclitaxel in Recurrent Platinum-Resistant Epithelial Ovarian and Peritoneal Cancers: A Phase III Study

    OpenAIRE

    Osman, Mohammed A.; Mohammad S. Elkady; Nasr, Khalid E.

    2016-01-01

    INTRODUCTION Treatment of recurrent platinum-resistant ovarian and peritoneal cancers represents a therapeutic challenge. The aim of this Phase III prospective study was to compare the survival benefits, objective response rate, and toxicities among patients treated by weekly paclitaxel with those who underwent three-weekly paclitaxel in recurrent platinum-resistant ovarian and peritoneal cancers. METHOD Patients with recurrent platinum-resistant ovarian and peritoneal cancer were allocated t...

  17. Expression and promotor methylation of p73 gene in ovarian epithelial tumors%p73基因在卵巢上皮性肿瘤中的表达及甲基化研究

    Institute of Scientific and Technical Information of China (English)

    张银丽; 郭小荣; 沈丹华; 成夜霞; 粱旭东; 陈云新; 王颖

    2012-01-01

    Objective To investigate the expression and promoter methylation status of p73 gene in ovarian epithelial tumors and their clinicopathological correlations.Methods Tissue microarrays ( TMA )consisting of 68 ovarian cancers,37 ovarian borderline tumors and 21 ovarian benign tumors were constructed.p73 expression was detected by immunohistochemistry (EnVision method).Fresh-frozen tissue samples from 13 cases of ovarian carcinomas and 5 cases of borderline tumors were evaluated for the presence of p73 promoter methylation using bisulfite sequencing.Results Overall,92.6% (63/68) ovarian carcinomas expressed p73,with a mean value of 32% (percentage of p73 positive cells in the tumor).The mean value of p73 expression rate (40%) in serous carcinoma ( 26/26 ) was higher than those of other cancer types (P =0.006),The mean value of p73 expression rate (40%) in type Ⅱ ovarian carcinoma was significantly higher than that in type Ⅰ ovarian carcinoma (24%,P =0.010).The expression of p73 was not associated with FIGO stage and histological grade ( both P > 0.05 ).The mean values of p73 expression in ovarian borderline tumor (30/37) and benign tumor ( 12/21 ) were 16% and 15%,respectively.Of the two groups,the mean value of p73 expression rate in serous type was higher than that in mucous type (P =0.003,P=0.026).Ovarian carcinomas had a higher level of p73 expression than borderline tumors and benign tumors ( both P < 0.05 ),while that between ovarian borderline tumors and benign tumors had no statistical difference ( P > 0.05 ).Among serous tumors (49/53),the mean value of p73 expression in the carcinoma group (26/26) was significantly higher than those in the borderline tumor group (12/14) and benign tumor group ( 11/13 ; P =0.024 and P =0.002,respectively),while that between borderline tumor group and benign tumor group had no statistical difference (P =0.428).Among mucous tumors ( 15/27 ),the mean value of p73 expression in carcinoma group (6/7) was

  18. Advanced Ovarian Dysgerminoma Infiltrating Both Ovaries and Uterus in a 7-Year-Old Girl

    Directory of Open Access Journals (Sweden)

    Nexhmi Hyseni

    2014-01-01

    Full Text Available Introduction. Ovarian dysgerminoma is a rare malignant ovarian germ cell tumor with its peak incidence in young women. Abdominal pain, abdominal distention, and the presence of a palpable mass are common symptoms at presentation. Depending on the FIGO stage at presentation the prognosis of dysgerminomas after surgical treatment, adjuvant chemotherapy, and radiotherapy is promising. Case Presentation. A 7-year-old girl was presented at our clinic with abdominal pain in all abdominal quadrants. Later the pain localized in the region of her right ovary. CT scan revealed a massive formation which was connected to her right ovary. Conclusion. Although malignant ovarian germ cell tumours are rare in children, physicians must always consider the possibility of MOGT-occurrences. The clinical symptoms might not be specific: abdominal pain, abdominal distention, nausea, and vomiting. In order to make a correct diagnosis the patients should undergo a complete clinical examination including radiological scans. Initial management is frequently surgery, followed by adjuvant chemotherapy and radiotherapy. Although disgerminoma is malignant tumor, the prognosis is promising.

  19. Local but no systemic immunomodulation by intraperitoneal treatment of advanced ovarian cancer with autologous T lymphocytes re-targeted by a bi-specific monoclonal antibody

    NARCIS (Netherlands)

    C.H.J. Lamers (Cor); R.L.H. Bolhuis (Reinder); S.O. Warnaar (Sven); G. Stoter (Gerrit); J.W. Gratama (Jan-Willem)

    1997-01-01

    textabstractWe have reported a 27% overall anti-tumor response using i.p. immunotherapy of advanced ovarian carcinoma with autologous, ex vivo expanded, T lymphocytes re-targeted with bi-specific monoclonal antibody OC/TR, combined with soluble OC/TR and low-dose recombinant interleukin-2 (IL-2). Th

  20. Laparoscopy to predict the result of primary cytoreductive surgery in advanced ovarian cancer patients (LapOvCa-trial): A multicentre randomized controlled study

    NARCIS (Netherlands)

    M.J. Rutten (Marianne); K.N. Gaarenstroom (Katja); T. van Gorp (Toon); H.S. van Meurs (Hannah); H.J.G. Arts (Henriette); P.M.M. Bossuyt (Patrick); H.G. ter Brugge (Henk); R.H. Hermans (Ralph); B.C. Opmeer; J.M.A. Pijnenborg (Johanna); H.W.R. Schreuder (Henk); E.M. Schutter (Eltjo); A.M. Spijkerboer (Anje); C.W.M. Wensveen (C. W M); P.L.M. Zusterzeel (Petra); B.W.J. Mol (Ben); G.G. Kenter (Gemma ); M.R. Buist (Marrije)

    2012-01-01

    textabstractBackground: Standard treatment of advanced ovarian cancer is surgery and chemotherapy. The goal of surgery is to remove all macroscopic tumour, as the amount of residual tumour is the most important prognostic factor for survival. When removal off all tumour is considered not feasible, n

  1. Laparoscopy to predict the result of primary cytoreductive surgery in advanced ovarian cancer patients (LapOvCa-trial): a multicentre randomized controlled study.

    NARCIS (Netherlands)

    Rutten, M.J.; Gaarenstroom, K.N.; Gorp, T. Van; Meurs, H.S. van; Arts, H.J.; Bossuyt, P.M.; Brugge, H.G. ter; Hermans, R.H.; Opmeer, B.C.; Pijnenborg, J.M.A.; Schreuder, H.W.B.; Schutter, E.M.; Spijkerboer, A.M.; Wensveen, C.W.; Zusterzeel, P.L.; Mol, B.W.; Kenter, G.G.; Buist, M.R.

    2012-01-01

    BACKGROUND: Standard treatment of advanced ovarian cancer is surgery and chemotherapy. The goal of surgery is to remove all macroscopic tumour, as the amount of residual tumour is the most important prognostic factor for survival. When removal off all tumour is considered not feasible, neoadjuvant c

  2. Laparoscopy to predict the result of primary cytoreductive surgery in advanced ovarian cancer patients (LapOvCa-trial) : a multicentre randomized controlled study

    NARCIS (Netherlands)

    Rutten, Marianne J.; Gaarenstroom, Katja N.; Van Gorp, Toon; van Meurs, Hannah S.; Arts, Henriette J. G.; Bossuyt, Patrick M.; Ter Brugge, Henk G.; Hermans, Ralph H. M.; Opmeer, Brent C.; Pijnenborg, Johanna M. A.; Schreuder, Henk W. R.; Schutter, Eltjo M. J.; Spijkerboer, Anje M.; Wensveen, Celesta W. M.; Zusterzeel, Petra; Mol, Ben Willem J.; Kenter, Gemma G.; Buist, Marrije R.

    2012-01-01

    Background: Standard treatment of advanced ovarian cancer is surgery and chemotherapy. The goal of surgery is to remove all macroscopic tumour, as the amount of residual tumour is the most important prognostic factor for survival. When removal off all tumour is considered not feasible, neoadjuvant c

  3. 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

  4. Clinico-pathological spectrum of primary ovarian malignant mixed mullerian tumors (OMMMT from a tertiary cancer institute: A series of 27 cases

    Directory of Open Access Journals (Sweden)

    Santosh Menon

    2013-01-01

    Full Text Available Aims and Objectives: To study the clinico-pathological characteristics of primary ovarian malignant mixed mullerian tumor (OMMMT and assess the prognostic factors associated with treatment outcome and survival. Materials and methods: The pathology database was searched for primary ovarian carcinosarcoma diagnosed and/or managed at our institute from period of January 2004 to July 2010. The histological sections were reviewed, with emphasis on type and grade of epithelial and sarcomatous components. The medical records were retrospectively analyzed for clinical details and follow up. Results: A total of 27 cases of primary ovarian carcinosarcoma were identified. The median age at diagnosis was 51 years. Fourteen patients had advanced stage (stage III and IV at presentation. Cytoreductive surgery was done in 18 cases, and 7 had received upfront chemotherapy. Histologically, 10 cases had epithelial predominance (> 50% epithelial component and 11 had sarcoma predominance. The most frequent epithelial component was endometroid type, and most common sarcoma component was rhabdomyosarcomatous. Hyaline droplets within sarcomatous stroma were seen prominently in 15 cases. Three cases showed germ cell /yolk sac-like areas. Eighteen cases had follow up with a median of 15 months (4-40 months. The recurrence-free survival in advanced stage and sarcoma predominant was 10.5 months in comparison to 13 months in early stage and epithelial predominant OMMMT. Conclusion: Primary ovarian carcinosarcoma is a rare biphasic malignancy with variable proportions of epithelial and spindle elements. Presence of hyaline droplets within spindle sarcoma in a biopsy from ovarian mass should alert the pathologists regarding MMMT. Advanced stage, suboptimal cytoreduction, and sarcoma predominant tumors are likely to have a worse outcome in ovarian MMMT.

  5. 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

  6. 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).

  7. Hydrogen Sulfide Prevents Advanced Glycation End-Products Induced Activation of the Epithelial Sodium Channel

    Directory of Open Access Journals (Sweden)

    Qiushi Wang

    2015-01-01

    Full Text Available Advanced glycation end-products (AGEs are complex and heterogeneous compounds implicated in diabetes. Sodium reabsorption through the epithelial sodium channel (ENaC at the distal nephron plays an important role in diabetic hypertension. Here, we report that H2S antagonizes AGEs-induced ENaC activation in A6 cells. ENaC open probability (PO in A6 cells was significantly increased by exogenous AGEs and that this AGEs-induced ENaC activity was abolished by NaHS (a donor of H2S and TEMPOL. Incubating A6 cells with the catalase inhibitor 3-aminotriazole (3-AT mimicked the effects of AGEs on ENaC activity, but did not induce any additive effect. We found that the expression levels of catalase were significantly reduced by AGEs and both AGEs and 3-AT facilitated ROS uptake in A6 cells, which were significantly inhibited by NaHS. The specific PTEN and PI3K inhibitors, BPV(pic  and LY294002, influence ENaC activity in AGEs-pretreated A6 cells. Moreover, after removal of AGEs from AGEs-pretreated A6 cells for 72 hours, ENaC PO remained at a high level, suggesting that an AGEs-related “metabolic memory” may be involved in sodium homeostasis. Our data, for the first time, show that H2S prevents AGEs-induced ENaC activation by targeting the ROS/PI3K/PTEN pathway.

  8. 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.

  9. Epigenetic analysis leads to identification of HNF1B as a subtype-specific susceptibility gene for ovarian cancer

    NARCIS (Netherlands)

    Shen, H.; Fridley, B.L.; Song, H.; Lawrenson, K.; Cunningham, J.M.; Ramus, S.J.; Cicek, M.S.; Tyrer, J.; Stram, D.; Larson, M.C.; Kobel, M.; Ziogas, A.; Zheng, W.; Yang, H.P.; Wu, A.H.; Wozniak, E.L.; Ling Woo, Y.; Winterhoff, B.; Wik, E.; Whittemore, A.S.; Wentzensen, N.; Palmieri Weber, R.; Vitonis, A.F.; Vincent, D.; Vierkant, R.A.; Vergote, I.; Berg, D. Van den; Altena, A.M. van; Tworoger, S.S.; Thompson, P.J.; Tessier, D.C.; Terry, K.L.; Teo, S.H.; Templeman, C.; Stram, D.O.; Southey, M.C.; Sieh, W.; Siddiqui, N.; Shvetsov, Y.B.; Shu, X.O.; Shridhar, V.; Wang-Gohrke, S.; Severi, G.; Schwaab, I.; Salvesen, H.B.; Rzepecka, I.K.; Runnebaum, I.B.; Rossing, M.A.; Rodriguez-Rodriguez, L.; Risch, H.A.; Renner, S.P.; Poole, E.M.; Pike, M.C.; Phelan, C.M.; Pelttari, L.M.; Pejovic, T.; Paul, J.; Orlow, I.; Zawiah Omar, S.; Olson, S.H.; Odunsi, K.; Nickels, S.; Nevanlinna, H.; Ness, R.B.; Narod, S.A.; Nakanishi, T.; Moysich, K.B.; Monteiro, A.N.; Moes-Sosnowska, J.; Modugno, F.; Menon, U.; McLaughlin, J.R.; McGuire, V.; Matsuo, K.; Mat Adenan, N.A.; Massuger, L.F.A.G.; Lurie, G.; Lundvall, L.; Lubinski, J.; Lissowska, J.; Levine, D.A.; Leminen, A.; Lee, A.W.; Le, N.D.; Lambrechts, S.; Lambrechts, D.; Kupryjanczyk, J.; Krakstad, C.; Konecny, G.E.; Kruger Kjaer, S.; Kiemeney, L.A.L.M.; Kelemen, L.E.; Keeney, G.L.; Karlan, B.Y.; Karevan, R.; Kalli, K.R.; Kajiyama, H.; Ji, B.T.; Jensen, A.; Jakubowska, A.; Iversen, E.; Hosono, S.; Hogdall, C.K.; Hogdall, E.; Hoatlin, M.; Hillemans, P.; Heitz, F.; Hein, R.; Harter, P.; Halle, M.K.; Hall, P.; Gronwald, J.; Gore, M.; Goodman, M.T.; Giles, G.G.; Gentry-Maharaj, A.; Garcia-Closas, M.; Flanagan, J.M.; Fasching, P.A.; Ekici, A.B.; Edwards, R.; Eccles, D.; Easton, D.F.; Durst, M.; Bois, A. du; Dork, T.; Doherty, J.A.; Despierre, E.; Dansonka-Mieszkowska, A.; Cybulski, C.; Cramer, D.W; Cook, L.S.; Chen, X.; Charbonneau, B.; Chang-Claude, J.; Campbell, I.; Butzow, R.; Bunker, C.H.; Brueggmann, D.; Brown, R.; Brooks-Wilson, A.; Brinton, L.A.; Bogdanova, N.; Block, M.S.; Benjamin, E.; Beesley, J.; Beckmann, M.W.; Bandera, E.V.; Baglietto, L.; Bacot, F.; Armasu, S.M.; Antonenkova, N.; Anton-Culver, H.; Aben, K.K.; Liang, D.

    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 com

  10. 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

  11. Ⅲ期上皮性卵巢癌患者的危险因素研究%Risk Factors of Patients with Stage ⅢEpithelial Ovarian Cancer

    Institute of Scientific and Technical Information of China (English)

    高慧; 李娟; 王文革

    2015-01-01

    Objective To explore the risk factors for recurrence of stage Ⅲepithelial ovarian cancer.Methods Clini-cal data of 90 cases of stage Ⅲepithelial ovarian cancer were retrospectively analyzed.Risk factors were evaluated by univariate and multivariate analysis.Results 90 patients were included in the study ,the mean age was (61 ±4.8) years.Univariate analy-sis showed that positive rate of peritoneal effusions oncology cells ,serum CA125,residual disease ,and lymph node ratio were asso-ciated with tumor recurrence.Patients with lymph node metastasis rate 0.15,3-year disease-free survival rate was 64% (P=0.011).Multivariate model found that lymph node ratio is the only independent risk factor for recurrence ,lymph node ratio can predict tumor recurrence.Conclusion Lymph node ratio is risk factor for recurrence of stage Ⅲepithelial ovarian cancer.%目的 探讨Ⅲ期上皮性卵巢癌患者复发的危险因素. 方法 回顾性分析90例Ⅲ期上皮性卵巢癌患者的临床资料. 采用单变量和多变量分析评估其复发的危险因素. 结果 90例患者纳入研究范围,平均年龄(61 ±4.8)岁.单因素分析确定了四个因素与肿瘤复发相关:腹腔积液肿瘤学细胞阳性率,血清CA125,残留病灶,淋巴结比例. 淋巴结比例0.15,3年无病生存率为64%(P=0.011). 多因素模型分析,发现淋巴结比例是肿瘤复发的唯一独立危险因素,淋巴结比例可以预测肿瘤复发. 结论 淋巴结比例是Ⅲ期上皮性卵巢癌肿瘤复发的重要危险因素.

  12. Tolerance of weekly metronomic paclitaxel and carboplatin as neoadjuvant chemotherapy in advanced ovarian cancer patients who are unlikely to tolerate 3 weekly paclitaxel and carboplatin

    OpenAIRE

    Dessai, S. B.; Chakraborty, S; Babu, T. V. S.; Nayanar, S.; A Bhattacharjee; Jones, J.; S Balasubramanian; Patil, Vijay M.

    2016-01-01

    Objective: There are little data regarding safety and effectiveness of neoadjuvant chemotherapy (NACT) in patients who are considered unfit for receiving 3 weekly paclitaxel and carboplatin. The aim of this study was to examine the toxicity and response rates of weekly paclitaxel and carboplatin as NACT in such cohort of patients. Methods: Study population included advanced ovarian cancer patients who were unlikely to tolerate 3 weekly paclitaxel and carboplatin and hence received weekly pacl...

  13. 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.

  14. ERCC1 mRNA Expression Level as a Prognostic Factor for Epithelial Ovarian Cancer%ERCC1基因mRNA表达水平在卵巢上皮性癌组织中的意义

    Institute of Scientific and Technical Information of China (English)

    蒋胜; 李力; 张玮; 唐兆前; 王琪; 姚德生; 张洁清; 阳志军

    2009-01-01

    Objective:To investigate the effect of excision repair cross-complementation group 1 (ERCC1) mR- NAexpression level on platinum-based chemotherapy response and survival time of epithelial ovarian cancer patients. And the alternative splicing variant lacking exon Ⅷ was especially investigated.Methods:Total RNA was isolated using Trizol reagent from 63 epithelial ovarian cancer tissues and then reverse-transcripted into cDNA. ERCC1 mRNA expression level was evaluated by TaqMan real-time quantitative RT-PCR and the alternative splicing variant lacking exon Ⅷ was especially investigated. All patients were follow-up to determine the survival time after surgery. Results: ①Total and the full length ERCC1 mRNA expression level in chemotherapy sensitive group was lower than in resistant group and the difference had statistical significance( P = 0.013, P=0.009, respectively). The alternative splicing variant lacking exon Ⅷ expression level had no statistical significance between the two groups( P = 0.085);② Low expression group of total and full length ERCC1 mRNA had longer survival time than high expression group and the difference had statistical significance( P = 0.012, P = 0.008, respectively). The alternative splicing variant lacking exon Ⅷ had no statistical significance between the high and low groups (P=0.07) .Conclusions:ERCC1 mRNA expression level was a prognostic factor for epithelial ovarian cancer patients receiving platinum-based chemotherapy. The alternative splicing variant lacking exon Ⅷ could not predict chemotherapy response and survival time and was not a prognostic factor for epithelial ovarian cancer patients.%目的:研究切除修复交叉互补基因1(ERCC1)在卵巢上皮性癌组织中的mRNA表达水平与患者对铂类药物化疗反应及生存期的关系,并探讨ERCC1基因缺失第Ⅷ外显子变异剪接体的临床意义.方法:使用TRIZol试剂提取63例卵巢上皮性癌组织总RNA,逆转录为cDNA后,TaqMan实时荧

  15. 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.

  16. Inhibitory effect of receptor for advanced glycation end products (RAGE) on the TGF-β-induced alveolar epithelial to mesenchymal transition

    OpenAIRE

    Song, Jeong Sup; Kang, Chun Mi; Park, Chan Kwon; Yoon, Hyung Kyu; Lee, Sook Young; Ahn, Joong Hyun; Moon, Hwa-Sik

    2011-01-01

    Idiopathic pulmonary fibrosis (IPF) is a lethal parenchymal lung disease characterized by myofibroblast proliferation. Alveolar epithelial cells (AECs) are thought to produce myofibroblasts through the epithelial to mesenchymal transition (EMT). Receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin superfamily of cell surface receptors whose activation is associated with renal fibrosis during diabetes and liver fibrosis. RAGE is expressed at low basal levels in...

  17. 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....

  18. Vaccine Therapy With Sargramostim (GM-CSF) in Treating Patients With Her-2 Positive Stage III-IV Breast Cancer or Ovarian Cancer

    Science.gov (United States)

    2016-05-02

    HER2-positive Breast Cancer; Stage III Ovarian Epithelial Cancer; Stage III Ovarian Germ Cell Tumor; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor

  19. 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...

  20. Molecular and Other Novel Advances in Treatment of Metastatic Epithelial and Medullary Thyroid Cancers

    OpenAIRE

    David Tai; Donald Poon

    2010-01-01

    An understanding of the mutations of the proto-oncogenes and tumor suppressor genes that occur in thyroid cancers should eventually explain the diverse clinical characteristics of these tumors and also direct therapy. Some insights have already emerged in the last decade; some abnormalities in tumor genes are consistently associated with specific clinical and pathologic findings. These genetic abnormalities usually represent somatic mutations in tumors of follicular epithelial origin, as oppo...

  1. 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 ...

  2. 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...... and 4% never had debulking surgery. Of the 288 patients (53%) referred to NACT, 44% were never debulked. Fourteen patients (3%) were referred to palliative treatment. The use of different imaging modalities, diagnostic laparoscopy, and laparotomy varied significantly among the centers. Diagnostic......-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....

  3. 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)

  4. 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.

  5. Laparoscopy to predict the result of primary cytoreductive surgery in advanced ovarian cancer patients (LapOvCa-trial: a multicentre randomized controlled study

    Directory of Open Access Journals (Sweden)

    Rutten Marianne J

    2012-01-01

    Full Text Available Abstract Background Standard treatment of advanced ovarian cancer is surgery and chemotherapy. The goal of surgery is to remove all macroscopic tumour, as the amount of residual tumour is the most important prognostic factor for survival. When removal off all tumour is considered not feasible, neoadjuvant chemotherapy (NACT in combination with interval debulking surgery (IDS is performed. Current methods of staging are not always accurate in predicting surgical outcome, since approximately 40% of patients will have more than 1 cm residual tumour after primary debulking surgery (PDS. In this study we aim to assess whether adding laparoscopy to the diagnostic work-up of patients suspected of advanced ovarian carcinoma may prevent unsuccessful primary debulking surgery for ovarian cancer. Methods Multicentre randomized controlled trial, including all gynaecologic oncologic centres in the Netherlands and their affiliated hospitals. Patients are eligible when they are planned for PDS after conventional staging. Participants are randomized between direct PDS or additional diagnostic laparoscopy. Depending on the result of laparoscopy patients are treated by PDS within three weeks, followed by six courses of platinum based chemotherapy or with NACT and IDS 3-4 weeks after three courses of chemotherapy, followed by another three courses of chemotherapy. Primary outcome measure is the proportion of PDS's leaving more than one centimetre tumour residual in each arm. In total 200 patients will be randomized. Data will be analysed according to intention to treat. Discussion Patients who have disease considered to be resectable to less than one centimetre should undergo PDS to improve prognosis. However, there is a need for better diagnostic procedures because the current number of debulking surgeries leaving more than one centimetre residual tumour is still high. Laparoscopy before starting treatment for ovarian cancer can be an additional diagnostic tool

  6. 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.

  7. Twist介导的上皮间质转化在卵巢癌组织中的作用%Effect of Twist on Epithelial-mesenchymal Transitions in Ovarian Cancer Tissue

    Institute of Scientific and Technical Information of China (English)

    王文双; 杨兴升; 马先莹

    2012-01-01

    目的 检测卵巢癌组织中Twist、E-cadherin及N-cadherin蛋白和mRNA的表达,探讨Twist介导的上皮间质转化(EMT)现象在卵巢癌发生、发展及转移中的作用.方法 分别采用免疫组化方法和RT-PCR法检测42例卵巢癌组织中介导EMT发生的转录因子Twist、E-cadherin及N-cadherin蛋白及其mRNA的表达,30例卵巢良性肿瘤组织作为对照.结果 卵巢癌组织中Twist、E-cadherin及N-cadherin蛋白阳性表达率分别为66.7%、28.6%和47.6%,卵巢良性肿瘤组织分别为26.7%、90.0%和13.3%,;Twist、E-cadherin及N-cadherin mRNA在卵巢癌组织中的表达量分别为1.49±0.53、0.82±0.24、1.55±0.56,卵巢良性肿瘤组织中分别为1.18±0.34、1.09±0.20、1.18±0.35.2种组织各项指标比较差异有统计学意义(P<0.05).Twist、E-cadherin及N-cadherin的表达与卵巢癌临床分期、分化程度及淋巴结转移有关(P<0.05).结论 在卵巢癌组织中,Twist、N-cadherin表达上调,E-cadherin表达下调,Twist介导的EMT可能与卵巢癌的侵袭转移有关.%Objective To observe the expression of Twist,E-cadherin and N-cadherin in ovarian cancer tissue and investigate the role of epithelial-mesenchymal transitions (EMT) in metastasis of ovarian cancer. Methods The expression of Twist,E-cadherin and N-cadherin proteins and their tnRNA in 42 ovarian cancer cases was detected by inununohistochemistry and RT-PCR,and 30 cases of ovarian benign tumor were selected as control group. Results The positive expression rates of Twist,E-cadherin and N-cadherin proteins in ovarian cancer tissue were 66.7%,28.6% and 47.6% respectively,whereas in the control group the positive expression rates were 26.7%,90.0% and 13.3%;The expression levels of Twist,E-cadherin and N-cadherin mRNA were 1.49±0.53,0.82±0.24 and 1.55±0.56,whereas in the control group the expression levels were 1.18±0.34,1.09±0.20 and 1.18±0.35. There was statistical difference between the two groups (P < 0

  8. CA-125 and Ceruloplasmin Levels in Ovarian Cancer Patients

    OpenAIRE

    Mangala Hegde; Yousef Rezaei Chianeh; Jeevan Shetty; Donald J. Fernandes; Pragna Rao

    2015-01-01

    Purpose: The initial stage of proliferation of epithelial ovarian carcinoma (EOCa) is usually asymptomatic. Due to the lack of sensitive and reliable markers in majority of patients the disease is widespread at the time of diagnosis. The reliable serum biomarkers currently accepted is CA125 but there is limitation in case of sensitivity of CA125 as it is detectable only in 50% of patients in stage I and 80% of patients with advanced stage. We have investigated a correlation between serum CA12...

  9. 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

  10. The association between socioeconomic status and tumour stage at diagnosis of ovarian cancer

    DEFF Research Database (Denmark)

    Præstegaard, Camilla; Kjær, Susanne Krüger; Nielsen, Thor S.S.;

    2016-01-01

    PURPOSE: Socioeconomic status (SES) is a known predictor of survival for several cancers and it has been suggested that SES differences affecting tumour stage at diagnosis may be the most important explanatory factor for this. However, only a limited number of studies have investigated SES...... differences in tumour stage at diagnosis of ovarian cancer. In a pooled analysis, we investigated whether SES as represented by level of education is predictive for advanced tumour stage at diagnosis of ovarian cancer, overall and by histotype. The effect of cigarette smoking and body mass index (BMI......) on the association was also evaluated. METHODS: From 18 case-control studies, we obtained information on 10,601 women diagnosed with epithelial ovarian cancer. Study specific odds ratios (ORs) with corresponding 95% confidence intervals (CI) were obtained from logistic regression models and combined into a pooled...

  11. 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...

  12. 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

  13. 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.

  14. The effect of neighborhood disadvantage on the racial disparity in ovarian cancer-specific survival in a large hospital-based study in Cook County, Illinois

    Directory of Open Access Journals (Sweden)

    Caryn E. Peterson

    2015-01-01

    Full Text Available This paper examines the effect of neighborhood disadvantage on racial disparities in ovarian cancer-specific survival. Despite treatment advances for ovarian cancer, survival remains shorter for African-American compared to White women. Neighborhood disadvantage is implicated in racial disparities across a variety of health outcomes and may contribute to racial disparities in ovarian cancer-specific survival. Data were obtained from 581 women (100 African-American and 481 White diagnosed with epithelial ovarian cancer between June 1, 1994, and December 31, 1998 in Cook County, Illinois, which includes the city of Chicago. Neighborhood disadvantage score at the time of diagnosis was calculated for each woman based on Browning and Cagney’s index of concentrated disadvantage. Cox proportional hazard models measured the association of self-identified African-American race with ovarian cancer-specific survival after adjusting for age, tumor characteristics, surgical debulking, and neighborhood disadvantage. There was a statistically significant negative association (-0.645 between ovarian cancer-specific survival and neighborhood disadvantage (p = 0.008. After adjusting for age and tumor characteristics, African-American women were more likely than Whites to die of ovarian cancer (HR = 1.59, p = 0.003. After accounting for neighborhood disadvantage, this risk was attenuated (HR = 1.32, p = 0.10. These findings demonstrate that neighborhood disadvantage is associated with ovarian cancer-specific survival and may contribute to the racial disparity in survival.

  15. 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

  16. 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

  17. 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

  18. Sustained platelet-sparing effect of weekly low dose paclitaxel allows effective, tolerable delivery of extended dose dense weekly carboplatin in platinum resistant/refractory epithelial ovarian cancer

    Directory of Open Access Journals (Sweden)

    Blagden Sarah

    2011-07-01

    Full Text Available Abstract Background Platinum agents have shown demonstrable activity in the treatment of patients with platinum resistant, recurrent ovarian cancer when delivered in a "dose-dense" fashion. However, the development of thrombocytopenia limits the weekly administration of carboplatin to no greater than AUC 2. Paclitaxel has a well-described platelet sparing effect however its use to explicitly provide thromboprotection in the context of dose dense carboplatin has not been explored. Methods We treated seven patients with platinum resistant ovarian cancer who had previously received paclitaxel or who had developed significant peripheral neuropathy precluding the use of further full dose weekly paclitaxel. Results We were able to deliver carboplatin AUC 3 and paclitaxel 20 mg/m2 with no thrombocytopenia or worsening of neuropathic side-effects, and with good activity. Conclusions We conclude that this regimen may be feasible and active, and could be formally developed as a "platinum-focussed dose-dense scaffold" into which targeted therapies that reverse platinum resistance can be incorporated, and merits further evaluation.

  19. 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

  20. 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

  1. C57BL/6 mouse model of epithelial ovarian cancer and its biological characteristics%C57BL/6小鼠上皮性卵巢癌模型的建立及其生物学特性

    Institute of Scientific and Technical Information of China (English)

    张祖娟; 李艺; 崔恒; 昌晓红; 陈新华; 叶雪

    2012-01-01

    Objective To establish epithelial ovarian cancer of peritoneal metastasis model and subcutaneous tumor model in immunocompetent C57BL/6 mice, thus to provide basis of diagnosis, treatment and prevention- related basic research for ovarian cancer. Methods Cultured inbred C57BL/6 mice poorly differentiated ovarian ade-nocarcinoma cell line ID- 8 in vitro. SPF grade C57BL/6 female mice (6~8 weeks) were inoculated with logarithmic phase of ID- 8 cells with 1X 107, 5 X 106, 1X 106 and 1 X 105 cells / dose intraperitoneally and subcutaneously into the flank. They were invided into 8 groups with 6 in each. Tumor formation rate, ascites, metastasis and survival rate were recorded. An additional set of 6 animals were injected intraperitoneally (5 X106 ID - 8 cells) and then sacrificed at different time intervals for necropsy and pathologic analysis. The remaining animals were sacrificed and examined just before they died. Results The tumor formation rate was 100%. In peritoneal tumor model group, the average survival time was (141 + 6. 7) d, (122.8 + 4.5) d, (83.4 + 7.2) d, (74.4 + 4.5) d in 1X 105, 1X 106, 5 X 106 and 1 X 107 ID- 8 cells group, with the tumor cell load increased, the survival time was significantly shorter (P<0. 05). In subcutaneous tumor group, nodule formation time was about 1 week in 1 X 107 cells group; 1 week in 5X106 cells group; 3 weeks in IX 106 cells group and 6 weeks in 1X105 cells group. As the tumor cells inoculation load increased, the diameter and volume of tumor increased significantly (P<0. 05). Conclusions C57BL/6 mice intraperitoneal ovarian cancer model is similar to human epithelial ovarian cancer stage Ⅲ and Ⅳ. The immune or drug therapy efficacy is easier observed in subcutaneous tumor model. Establishing the ID- 8 cells ovarian cancer tumor model in immunocompetent C57BL/6 mice is helpful for clinical study of the treatment of ovarian cancer and immunological study of molecular models.%目的 在免疫功能正常的C57BL/6小

  2. Outcome in Advanced Ovarian Cancer following an Appropriate and Comprehensive Effort at Upfront Cytoreduction: A Twenty-Year Experience in a Single Cancer Institute

    Directory of Open Access Journals (Sweden)

    Anne Marszalek

    2010-01-01

    Full Text Available Objectives. The purpose of this retrospective evaluation of advanced-stage ovarian cancer patients was to compare outcome with published findings from other centers and to discuss future options for the management of advanced ovarian carcinoma patients. Methods. A retrospective series of 340 patients with a mean age of 58 years (range: 17–88 treated for FIGO stage III and IV ovarian cancer between January 1985 and January 2005 was reviewed. All patients had primary cytoreductive surgery, without extensive bowel, peritoneal, or systematic lymph node resection, thereby allowing initiation of chemotherapy without delay. Chemotherapy consisted of cisplatin-based chemotherapy in combination with alkylating agents before 2000, whereas carboplatin and paclitaxel regimes were generally used after 1999-2000. Overall survival and disease-free survival were analyzed by the Kaplan-Meier method and the log-rank test. Results. With a mean followup of 101 months (range: 5 to 203, 280 events (recurrence or death were observed and 245 patients (72% had died. The mortality and morbidity related to surgery were low. The main prognostic factor for overall survival was postoperative residual disease (P<.0002, while the main prognostic factor for disease-free survival was histological tumor type (P<.0007. Multivariate analysis identified three significant risk factors: optimal surgery (RR=2.2 for suboptimal surgery, menopausal status (RR=1.47 for postmenopausal women, and presence of a taxane in the chemotherapy combination (RR=0.72. Conclusion. These results confirm that optimal surgery defined by an appropriate and comprehensive effort at upfront cytoreduction limits morbidity related to the surgical procedure and allows initiation of chemotherapy without any negative impact on survival. The impact of neoadjuvant chemotherapy to improve resectability while lowering the morbidity of the surgical procedure is discussed.

  3. PHASE-II STUDY OF HIGH-DOSE MEGESTROL-ACETATE IN PATIENTS WITH ADVANCED OVARIAN-CARCINOMA

    NARCIS (Netherlands)

    VEENHOF, CHN; VANDERBURG, MEL; NOOY, M; AALDERS, JG; PECORELLI, S; OLIVEIRA, CF; ROTMENSZ, N; VERMORKEN, JB

    1994-01-01

    The EORTC Gynaecological Cancer Cooperative Group conducted a phase II study of high dose oral megestrol acetate: 800 mg/day for 1 month followed by 400 mg/day as maintenance treatment, in heavily pretreated patients with ovarian cancer. Of 72 patients included in this study, 54 were fully evaluable

  4. A randomized phase II study of paclitaxel with carboplatin +/- amifostine as first line treatment in advanced ovarian carcinoma

    NARCIS (Netherlands)

    De Vos, F Y F L; Bos, A M E; Schaapveld, M; de Swart, C A M; de Graaf, H; van der Zee, A G J; Boezen, H M; de Vries, E G E; Willemse, P H B

    2005-01-01

    OBJECTIVE: Will amifostine (A) protect against chemotherapy-induced neuro- and myelotoxicity. PATIENTS AND METHODS: Ninety ovarian cancer patients were randomized to receive standard paclitaxel + carboplatin without (PC) or preceded by amifostine 740 mg/m(2) (PC + A). RESULTS: The mean baseline valu

  5. Prognostic significance of tumor-infiltrating T-lymphocytes in primary and metastatic lesions of advanced stage ovarian cancer

    NARCIS (Netherlands)

    Leffers, Ninke; Gooden, Marloes J. M.; de Jong, Renske A.; Hoogeboom, Baukje-Nynke; ten Hoor, Klaske A.; Hollema, Harry; Boezen, H. Marieke; van der Zee, Ate G. J.; Daemen, Toos; Nijman, Hans W.

    2009-01-01

    PURPOSE: Ovarian cancer patients with intra-tumoral CD3(+) T-lymphocytes in primary tumor tissue have a better prognosis. This study aims to analyze the presence and relative influence of three important T-lymphocyte subsets, tumor-infiltrating CD8(+) cytotoxic T-lymphocytes (CTL), CD45R0(+) memory

  6. Isolation,identification and clinical significance of ascites-derived exosomes from patients with ovarian epithelial cancer%卵巢上皮性癌患者腹水中外来体的分离和鉴定及临床意义

    Institute of Scientific and Technical Information of China (English)

    彭澎; 游燕; 沈铿

    2009-01-01

    Objective To isolate and identify the aseites-derived exosomes from patients with ovarian epithelial carcinoma,and explore the relationship between exosomes and the prognosis of ovarian epithelial carcinoma.Methods Ascites-derived egosomes were isolated by ultraeentrifugation on sucrose and D2O gradients from 41 ovarian epithelial carcinoma patients,and identified by transmission electron microscope and western blot analyses.Ascites-derived exosomes were evaluated for effect on prognosis of ovarian epithelial carcinoma.Resulls Exosomes were isolated and purified from the ascites in 85% (35/41)of ovarian epithelial carcinoma patients;major histocompability complex-I(MHC-I)could be detected in 100%(35/35)of the aseites-derived exosomes samples,heat shock protein-70(Hsp70)in 91%(32/35),and CD81 in 86%(30/35).The patients with positive ascites-derived exosomes had no significant difference in age,pathological type and the degree of differentiation of tumor,surgical-pathological staging,the optimal operation and the responsibility to chemotherapy(P>0.05).The patients with positive ascites-derived exosomes,the reduction of CA125 level after cytoreduetive surgery was(66±27)%,which was more than that of the patients without ascites-derived exosomes(37±86)%and all the whole patients not considering the condition of exosomes(61±44)%(P0.05).卵巢癌患者行肿瘤细胞减火术后,腹水中外来体阳性患者血清CA125水平平均下降幅度为(66±27)%,明显高于外来体阴性患者的(37±86)%及卵巢痛患者整体的(61±44)%(P<0.01);且这种差异与手术是否彻底无关(P<0.01).结论 卵巢癌患者腹水中能够分离到典型的外来体.外来体的存在与卵巢癌患者肿瘤细胞减灭术后CA125水平下降幅度有关,但与其预后的关系有待进一步研究.

  7. FISH技术检测卵巢上皮性肿瘤组织CCND1表达及临床意义%Fluorescence in situ hybridization analysis of expression and clinic significance of CCND1 gene in epithelial ovarian neoplasms

    Institute of Scientific and Technical Information of China (English)

    张志磊; 鲁强; 马德花; 赵淑萍

    2011-01-01

    目的:探讨荧光原位杂交技术(FISH)检测卵巢上皮性肿瘤中CCND1基因的表达及其临床意义.方法:应用FISH技术检测45例卵巢正常组织和113例卵巢上皮性肿瘤中CCND1基因的表达.结果:CCND1基因在正常卵巢组织、卵巢良性肿瘤、交界性肿瘤及恶性肿瘤中的扩增表达率分别为11.1%、33.3%、43.5%和66.1%,恶性组的表达扩增率明显高于其他组,差异有统计学意义,P<0.01;卵巢上皮性癌组织中CCND1基因的表达扩增率与病理分级、临床病理分期及癌组织转移明显相关,差异有统计学意义(P<0.05),但与年龄、病理学类型无相关性,P>0.05.结论:CCND1基因的扩增在卵巢肿瘤的发生发展中起重要作用,且与卵巢癌的病理分级、临床分期及癌组织的转移有关,可用以预测肿瘤患者的预后.%OBJECTIVE: To investigation the CCND1 gene and its clinical significance in epithelial ovarian tumors. METHODS: The expression of CCND1 gene in 113 cases of epithelial ovarian tumors and 40 cases of normal ovarian tissue were detected by fluorescence in situ hybridization. RESULTS: Positive expression rates of the CCND1 gene in normal ovarian tissue, benign tumor, borderline tumor and ovarian cancer were separately 11.1%, 33.3%, 43.5%, 66.1%. Compared with other groups , positive expression rate of ovarian cancer was higher (P0. 05). CONCLUSIONS: The CCDN1 gene plays a role in the development of ovarian cancer. The positive expression rate of it may serve as a new prognostic maker for ovarian tumor.

  8. 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

  9. BLAP-Tags, TUBEs and DUB-Chips: Combined Novel Technologies will Advance Molecular Epithelial Physiology

    OpenAIRE

    Hamilton, Kirk L.

    2012-01-01

    The field of ubiquitylation and deubiquitylation of proteins in molecular physiology is growing at a rapid rate. Our understanding of molecular physiology of these processes may become limited by the advancement of technologies that scientists can employ. Therefore, it is important to approach physiological questions of ubiquitylation and deubiquitylation of proteins from a multiple methodological direction. Indeed, the role of ubiquitylation and deubiquitylation of proteins in cellular funct...

  10. BLAP-tags, TUBEs and DUB-Chips: Combined novel technologies will advance molecular epithelial physiology

    OpenAIRE

    KirkLHamilton

    2012-01-01

    The field of ubiquitylation and dubiquitylation of proteins in molecular physiology is growing at a rapid rate. Our understanding of molecular physiology of these processes may become limited by the advancement of technologies that scientists can employ. Therefore, it is important to approach physiological questions of ubiquitylation and dubiquitylation of proteins from a multiple methodological direction. Indeed, the role of ubiquitylation and dubiquitylation of proteins in cellular functio...

  11. 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.

  12. 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。

  13. 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

  14. 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

  15. BLAP-tags, TUBEs and DUB-Chips: Combined novel technologies will advance molecular epithelial physiology

    Directory of Open Access Journals (Sweden)

    Kirk L Hamilton

    2012-05-01

    Full Text Available The field of ubiquitylation and dubiquitylation of proteins in molecular physiology is growing at a rapid rate. Our understanding of molecular physiology of these processes may become limited by the advancement of technologies that scientists can employ. Therefore, it is important to approach physiological questions of ubiquitylation and dubiquitylation of proteins from a multiple methodological direction. Indeed, the role of ubiquitylation and dubiquitylation of proteins in cellular function has been implicated in the pathophysiology of human diseases including cancer, viral diseases and neurodegenerative disorders. There are many modulators (activators and inhibitors of ubiquitylation and dubiquitylation. Therefore, the link is being able to rapidly assess potential modulators of ubiquitylation and dubiquitylation and determine which specific modulators play a role(s within a particular physiological setting. After the specific modulators have been identified, further experimentation is required to assess the downstream use as potential clinical target for a particular disease. The first step is to identify the specific modulators. This perspective highlights a multi-prong technologies approach that uses three novel techn

  16. BLAP-Tags, TUBEs and DUB-Chips: Combined Novel Technologies will Advance Molecular Epithelial Physiology.

    Science.gov (United States)

    Hamilton, Kirk L

    2012-01-01

    The field of ubiquitylation and deubiquitylation of proteins in molecular physiology is growing at a rapid rate. Our understanding of molecular physiology of these processes may become limited by the advancement of technologies that scientists can employ. Therefore, it is important to approach physiological questions of ubiquitylation and deubiquitylation of proteins from a multiple methodological direction. Indeed, the role of ubiquitylation and deubiquitylation of proteins in cellular function has been implicated in the pathophysiology of human diseases including cancer, viral diseases, and neurodegenerative disorders. There are many modulators (activators and inhibitors) of ubiquitylation and deubiquitylation. Therefore, the link is being able to rapidly assess potential modulators of ubiquitylation and deubiquitylation and determine which specific modulators play a role(s) within a particular physiological setting. After the specific modulators have been identified, further experimentation is required to assess the downstream use as potential clinical targets for a particular disease. The first step is to identify the specific modulators. This perspective highlights a multi-prong technologies approach that uses three novel technologies (BLAP-tagged proteins, TUBES, and DUB-Chips) that can rapidly identify a number of potential candidates that modulate ubiquitylation and deubiquitylation of cellular proteins. PMID:22615701

  17. Ovarian cystadenofibroma: A masquerader of malignancy

    OpenAIRE

    Wasnik Ashish; Elsayes Khaled

    2010-01-01

    Ovarian cystadenofibroma is a relatively rare benign ovarian tumor that contains both epithelial and fibrous stromal components. The appearance of cystadenofibroma on imaging is often complex; cystic- to solid-appearing masses may be visualized and it often resembles a malignant tumor. Owing to the fibrous component of this tumor, MRI shows low-signal intensity on T2W images. This finding may help a radiologist make a preoperative diagnosis of this tumor and thus perhaps avoid aggressive surg...

  18. Bleomycin cardiotoxicity during chemotherapy for an ovarian germ cell tumor

    OpenAIRE

    Didagelos, M; Boutis, A; Diamantopoulos, N; Sotiriadou, M; Fotiou, C

    2013-01-01

    Introduction: Platinum-based chemotherapeutic regimens, including BEP (bleomycin, etoposide, cisplatin) represent the standard of care, first line therapy in non-epithelial ovarian tumours. Cardiovascular toxicity is a rare adverse effect of bleomycin.

  19. 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。

  20. 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

  1. 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

  2. Dietary energy balance modulates ovarian cancer progression and metastasis

    OpenAIRE

    Al-Wahab, Zaid; Tebbe, Calvin; Chhina, Jasdeep; Dar, Sajad A.; Morris, Robert T.; Ali-Fehmi, Rouba; Giri, Shailendra; Munkarah, Adnan R.; Rattan, Ramandeep

    2014-01-01

    A high energy balance, or caloric excess, accounts as a tumor promoting factor, while a negative energy balance via caloric restriction, has been shown to delay cancer progression. The effect of energy balance on ovarian cancer progression was investigated in an isogeneic immunocompetent mouse model of epithelial ovarian cancer kept on a regimen of regular diet, high energy diet (HED) and calorie restricted diet (CRD), prior to inoculating the animals intraperitoneally with the mouse ovarian ...

  3. Risk factors for ovarian cancer: a case-control study.

    OpenAIRE

    Booth, M.; Beral, V; SMITH, P.

    1989-01-01

    A hospital-based case-control study of ovarian cancer was conducted in London and Oxford between October 1978 and February 1983. Menstrual characteristics, reproductive and contraceptive history and history of exposure to various environmental factors were compared between 235 women with histologically diagnosed epithelial ovarian cancer and 451 controls. High gravidity, hysterectomy, female sterilisation and oral contraceptive use were associated with a reduced risk of ovarian cancer. Infert...

  4. HIPEC ROC I: a phase I study of cisplatin administered as hyperthermic intraoperative intraperitoneal chemoperfusion followed by postoperative intravenous platinum-based chemotherapy in patients with platinum-sensitive recurrent epithelial ovarian cancer.

    Science.gov (United States)

    Zivanovic, Oliver; Abramian, Alina; Kullmann, Maximilian; Fuhrmann, Christine; Coch, Christoph; Hoeller, Tobias; Ruehs, Hauke; Keyver-Paik, Mignon Denise; Rudlowski, Christian; Weber, Stefan; Kiefer, Nicholas; Poelcher, Martin L; Thiesler, Thore; Rostamzadeh, Babak; Mallmann, Michael; Schaefer, Nico; Permantier, Maryse; Latten, Sandra; Kalff, Joerg; Thomale, Juergen; Jaehde, Ulrich; Kuhn, Walther C

    2015-02-01

    This phase I study tested the safety, feasibility, pharmacokinetics and pharmacodynamics of cisplatin administered as hyperthermic intraoperative intraperitoneal chemoperfusion (HIPEC) in patients with platinum-sensitive recurrent epithelial ovarian cancer (EOC) undergoing secondary cytoreductive surgery followed by postoperative platinum-based intravenous chemotherapy. Twelve patients with operable, recurrent platinum-sensitive EOC (recurrence ≥6 months after first-line therapy) were included according to the classical 3+3 dose-escalation design at three dose levels-60, 80 and 100 mg/m(2). After surgical cytoreduction, a single dose of cisplatin was administered via HIPEC for 90 min at 41-43°C. Postoperatively, all patients were treated with standard intravenous platinum-based combination chemotherapy. One of six patients experienced a dose-limiting toxicity (grade 3 renal toxicity) at a dose of 100 mg/m(2). The remaining five patients treated with 100 mg/m(2) tolerated their treatment well. The recommended phase II dose was established at 100 mg/m(2). The mean peritoneal-to-plasma AUC ratio was 19·5 at the highest dose level. Cisplatin-induced DNA adducts were confirmed in tumor samples. Common postoperative grade 1-3 toxicities included fatigue, postoperative pain, nausea, and surgical site infection. The ability to administer standard intravenous platinum-based chemotherapy after HIPEC was uncompromised. Cisplatin administered as HIPEC at a dose of 100 mg/m(2) has an acceptable safety profile in selected patients undergoing secondary cytoreductive surgery for platinum-sensitive recurrent EOC. Favorable pharmacokinetic and pharmacodynamic properties of HIPEC with cisplatin were confirmed at all dose levels, especially at 100 mg/m(2). The results are encouraging to determine the efficacy of HIPEC as a complementary treatment in patients with EOC. PMID:24895230

  5. Cyclophosphamide or Denileukin Diftitox Followed By Expanding a Patient's Own T Cells in the Laboratory in Treating Patients With HER-2/Neu Overexpressing Metastatic Breast Cancer, Ovarian Cancer, or Non-Small Cell Lung Cancer Previously Treated With HER-2/Neu Vaccine

    Science.gov (United States)

    2014-11-07

    HER2-positive Breast Cancer; Recurrent Breast Cancer; Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Stage IV Breast Cancer; Stage IV Non-small Cell Lung Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor

  6. 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.

  7. 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

  8. 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

  9. 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.

  10. Risk of ovarian cancer in women with first-degree relatives with cancer

    DEFF Research Database (Denmark)

    Soegaard, Marie; Frederiksen, Kirsten; Jensen, Allan;

    2009-01-01

    OBJECTIVE: To assess the risk of ovarian cancer in women with first-degree relatives with cancer at one of the four most frequent hereditary sites based on validated cancer diagnoses and to examine the association according to age at diagnosis of ovarian cancer and histology. DESIGN: Case......-control study. SETTING AND POPULATION: First-degree relatives of 554 women with invasive epithelial ovarian cancer and 1,564 controls were included. METHODS: Analyses were performed using multiple logistic regression models. RESULTS: Ovarian cancer in a first-degree relative was significantly associated...... with ovarian cancer family history tended to be with non-mucinous tumors. Breast cancer in one first-degree female relative was not significantly associated with risk of ovarian cancer. CONCLUSION: Ovarian cancer in a first-degree relative is a very strong predictor of epithelial ovarian cancer, especially...

  11. 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

  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. Role of the polypeptide N-acetylgalactosaminyltransferase 3 in ovarian cancer progression: possible implications in abnormal mucin O-glycosylation.

    Science.gov (United States)

    Wang, Zhi-Qiang; Bachvarova, Magdalena; Morin, Chantale; Plante, Marie; Gregoire, Jean; Renaud, Marie-Claude; Sebastianelli, Alexandra; Bachvarov, Dimcho

    2014-01-30

    Previously, we have identified the polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3) 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 GALNT3 is strongly overexpressed in HG serous EOC tumors as compared to normal ovarian tissue. Moreover, the GALNT3 expression significantly correlated with shorter progression-free survival (PFS) intervals in epithelial ovarian cancer (EOC) patients with advanced disease. Knockdown of the GALNT3 expression in EOC cells led to sharp decrease of cell proliferation and induced S-phase cell cycle arrest. Additionally, GALNT3 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 GALNT3 suppression, while some tumor suppressor genes were induced. Moreover, GALNT3 downregulation was associated with reduced MUC1 protein expression in EOC cells, probably related to destabilization of the MUC1 protein due to lack of GALNT3 glycosylation activity. GALNT3 knockdown was also accompanied with increase of the cell adhesion molecules β-catenin and E-cadherin, which are normally suppressed by MUC1 in cancer, thus supporting the role of the GALNT3-MUC1 axis in EOC invasion. Taken together, our data are indicative for a strong oncogenic potential of the GALNT3 gene in advanced EOC and identify this transferase as a novel EOC biomarker and putative EOC therapeutic target. Our findings also suggest that GALNT3 overexpression might contribute to EOC progression through aberrant mucin O-glycosylation.

  14. Clinicopathological and IHC study (estrogen receptors, progesterone receptor, HER2/NEU in malignant ovarian tumors

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    Bhagyalakshmi Atla

    2016-04-01

    Results: The mean age at presentation was 39.5 years, majority of the ovarian carcinomas occurred in the age group of third and fifth decade (20/42. The commonest clinical presentation was mass per abdomen. The commonest histological type was malignant surface epithelial tumors (25/42, 59.55% of which serous cystadenocarcinioma was the predominant tumor followed by germ cell tumors (9/42, 21.42%. Ascites was associated with higher grade and higher stage of tumors. Majority of the ovarian carcinomas were of grade 2 (57.14% and stage 3 (35.7%. ER was positive in (9/42 21.42%, PR was positive in (10/42 23.8% and Her2/neu was equivocal in (3/42 7.14% of ovarian carcinomas. ER, PR and Her2 showed similar expression, with higher expression in cases of advanced disease. Conclusions: The expression of steroid hormonal receptors in ovarian cancers paves way for antihormonal therapy/ targeted therapy and this requires more number of studies with larger sample size. [Int J Res Med Sci 2016; 4(4.000: 1068-1073

  15. Migration and invasion is inhibited by silencing ROR1 and ROR2 in chemoresistant ovarian cancer.

    Science.gov (United States)

    Henry, C E; Llamosas, E; Djordjevic, A; Hacker, N F; Ford, C E

    2016-01-01

    Ovarian cancer survival remains poor despite recent advances in our understanding of genetic profiles. Unfortunately, the majority of ovarian cancer patients have recurrent disease after chemotherapy and lack other treatment options. Wnt signalling has been extensively implicated in cancer progression and chemoresistance. Therefore, we investigated the previously described Wnt receptors ROR1 and ROR2 as regulators of epithelial-to-mesenchymal transition (EMT) in a clinically relevant cell line model. The parental A2780- and cisplatin-resistant A2780-cis cell lines were used as a model of ovarian cancer chemoresistance. Proliferation, adhesion, migration and invasion were measured after transient overexpression of ROR1 and ROR2 in the parental A2780 cell line, and silencing of ROR1 and ROR2 in the A2780-cis cell line. Here we show that ROR1 and ROR2 expression is increased in A2780-cis cells, alongside β-catenin-independent Wnt targets. Knockdown of ROR1 and ROR2 significantly inhibited cell migration and invasion and simultaneous knockdown of ROR1 and ROR2 significantly sensitised cells to cisplatin, whilereas ROR overexpression in the parental cell line increased cell invasion. Therefore, ROR1 and ROR2 have the potential as novel drug targets in metastatic and recurrent ovarian cancer patients. PMID:27239958

  16. Docetaxel Influences Autocrine of Transforming Growth Factors and Induces Apoptosis in Human Ovarian Cancer Cell Line AO

    Institute of Scientific and Technical Information of China (English)

    Yan Zhang; Ya-li Hu; Yun-ying Cheng

    2006-01-01

    @@ Ovarian cancer is the second most common malignancy of female reproductive tract. Docetaxel shows good clinical efficacy against ovarian cancer.This present study was to investigate the role of docetaxel on apoptosis of ovarian cancer epithelial cell line AO as well as the secretion of transforming growth factor (TGF)-α and TGF-β1 during apoptosis.

  17. 人卵巢癌细胞株侧群细胞的生物学特征%Biological characteristics of the side population of human ovarian epithelial cancer cell line

    Institute of Scientific and Technical Information of China (English)

    林琳; 王沂峰; 黄奕俊

    2008-01-01

    an anti-ABCG2 monoclonal antibody. Results Flow cytometric analysis confirmed the presence of small subpopulations of cells excluding Hoechst dye in OVCAP,3 cells (2. 0% ) in a verapamil-sensitive manner. Hoechst dye uptake in OVCAR3 cells was enhanced by addition of verapamil, consistent with activity of ABCG2 protein. CFE of both SP and non-SP was 46.17%±23.27% and 6.17%±3.06%, respectively(P<0. 05). The Hoechst dye excluding SP cells exhibited immunoreactivity to stem cell markers ABCG2, demonstrated by Western blotting. They could grow in soft agar plate and formed cell sphere. Conclusions Human epithelial ovarian carcinoma cell line OVCAR3 contains a small subpoptdation of cells that exhibits a cancer stem cell-like phenotype. Special significance is the expression of ABCG2 in human tumor cells, a calcium-sensitive cell surface protein that acts to exclude Hoechst dye. These cells play a principal role in maintaining cancer cell line. It can be seen that cancer cell lines are potentially useful tools for investigating the characteristics of CSCs under controlled experimental conditions.

  18. Hormone therapy and different ovarian cancers

    DEFF Research Database (Denmark)

    Mørch, Lina Steinrud; Løkkegaard, Ellen; Andreasen, Anne Helms;

    2012-01-01

    Postmenopausal hormone therapy use increases the risk of ovarian cancer. In the present study, the authors examined the risks of different histologic types of ovarian cancer associated with hormone therapy. Using Danish national registers, the authors identified 909,946 women who were followed from...... 1995-2005. The women were 50-79 years of age and had no prior hormone-sensitive cancers or bilateral oophorectomy. Hormone therapy prescription data were obtained from the National Register of Medicinal Product Statistics. The National Cancer and Pathology Register provided data on ovarian cancers......, including information about tumor histology. The authors performed Poisson regression analyses that included hormone exposures and confounders as time-dependent covariates. In an average of 8.0 years of follow up, 2,681 cases of epithelial ovarian cancer were detected. Compared with never users, women...

  19. Olaparib in the management of ovarian cancer

    Directory of Open Access Journals (Sweden)

    Bixel K

    2015-08-01

    Full Text Available Kristin Bixel,1 John L Hays2 1Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, 2Department of Hematology Oncology, Ohio State University, Columbus, OH, USAAbstract: Alterations in the homologous repair pathway are thought to occur in 30%–50% of epithelial ovarian cancers. Cells deficient in homologous recombination rely on alternative pathways for DNA repair in order to survive, thereby providing a potential target for therapy. Olaparib, a poly(ADP-ribose polymerase (PARP inhibitor, capitalizes on this concept and is the first drug in its class approved for patients with ovarian cancer. This review article will provide an overview of the BRCA genes and homologous recombination, the role of PARP in DNA repair and the biological rationale for the use of PARP inhibitors as cancer therapy, and ultimately will focus on the use of olaparib in the management of ovarian cancer.Keywords: olaparib, ovarian cancer, PARP inhibitor

  20. Genetic and molecular changes in ovarian cancer

    Science.gov (United States)

    Hollis, Robert L; Gourley, Charlie

    2016-01-01

    Epithelial ovarian cancer represents the most lethal gynecological malignancy in the developed world, and can be divided into five main histological subtypes: high grade serous, endometrioid, clear cell, mucinous and low grade serous. These subtypes represent distinct disease entities, both clinically and at the molecular level. Molecular analysis has revealed significant genetic heterogeneity in ovarian cancer, particularly within the high grade serous subtype. As such, this subtype has been the focus of much research effort to date, revealing molecular subgroups at both the genomic and transcriptomic level that have clinical implications. However, stratification of ovarian cancer patients based on the underlying biology of their disease remains in its infancy. Here, we summarize the molecular changes that characterize the five main ovarian cancer subtypes, highlight potential opportunities for targeted therapeutic intervention and outline priorities for future research.

  1. Decreased expression of RNA interference machinery, Dicer and Drosha, is associated with poor outcome in ovarian cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Merritt, William M.; Lin, Yvonne G.; Han, Liz Y.; Kamat, Aparna A.; Spannuth, Whitney A.; Schmandt, Rosemarie; Urbauer, Diana; Pennacchio, Len A.; Cheng, Jan-Fang; Zeidan, Alexandra; Wang, Hua; Mueller, Peter; Lenburg, Marc E.; Gray, Joe W.; Mok, Samuel; Birrer, Michael J.; Lopez-Berestein, Gabriel; Coleman, Robert L.; Bar-Eli, Menashe; Sood, Anil K.

    2008-05-06

    The clinical and functional significance of RNA interference (RNAi) machinery, Dicer and Drosha, in ovarian cancer is not known and was examined. Dicer and Drosha expression was measured in ovarian cancer cell lines (n=8) and invasive epithelial ovarian cancer specimens (n=111) and correlated with clinical outcome. Validation was performed with previously published cohorts of ovarian, breast, and lung cancer patients. Anti-Galectin-3 siRNA and shRNA transfections were used for in vitro functional studies. Dicer and Drosha mRNA and protein levels were decreased in 37% to 63% of ovarian cancer cell lines and in 60% and 51% of human ovarian cancer specimens, respectively. Low Dicer was significantly associated with advanced tumor stage (p=0.007), and low Drosha with suboptimal surgical cytoreduction (p=0.02). Tumors with both high Dicer and Drosha were associated with increased median patient survival (>11 years vs. 2.66 years for other groups; p<0.001). In multivariate analysis, high Dicer (HR=0.48; p=0.02), high-grade histology (HR=2.46; p=0.03), and poor chemoresponse (HR=3.95; p<0.001) were identified as independent predictors of disease-specific survival. Findings of poor clinical outcome with low Dicer expression were validated in separate cohorts of cancer patients. Galectin-3 silencing with siRNA transfection was superior to shRNA in cell lines with low Dicer (78-95% vs. 4-8% compared to non-targeting sequences), and similar in cell lines with high Dicer. Our findings demonstrate the clinical and functional impact of RNAi machinery alterations in ovarian carcinoma and support the use of siRNA constructs that do not require endogenous Dicer and Drosha for therapeutic applications.

  2. Tolerance of weekly metronomic paclitaxel and carboplatin as neoadjuvant chemotherapy in advanced ovarian cancer patients who are unlikely to tolerate 3 weekly paclitaxel and carboplatin

    Directory of Open Access Journals (Sweden)

    S B Dessai

    2016-01-01

    Full Text Available Objective: There are little data regarding safety and effectiveness of neoadjuvant chemotherapy (NACT in patients who are considered unfit for receiving 3 weekly paclitaxel and carboplatin. The aim of this study was to examine the toxicity and response rates of weekly paclitaxel and carboplatin as NACT in such cohort of patients. Methods: Study population included advanced ovarian cancer patients who were unlikely to tolerate 3 weekly paclitaxel and carboplatin and hence received weekly paclitaxel (80 mg/m 2 and carboplatin AUC-2 as NACT. The data regarding the baseline characteristics, chemotherapy tolerance, completion rates, toxicity (Common Terminology Criteria for Adverse Events version 4.02, and radiological response rates are presented. SPSS version 16 was used for analysis. Descriptive statistics is presented. Results: Eleven patients received this schedule. Nine patients completed nine cycles of NACT. Except one, all patients completed NACT with an average relative dose intensity of >0.8. There was no chemotherapy-related mortality. Grade 3-4 life-threatening complications were seen in two patients. The post NACT response rate was 100%. Conclusions: Weekly paclitaxel and carboplatin chemotherapy is safe and efficacious in patients who are unsuitable for 3 weekly paclitaxel and carboplatin chemotherapy schedules.

  3. Poor ovarian reserve

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    Padma Rekha Jirge

    2016-01-01

    Full Text Available Poor ovarian reserve (POR is an important limiting factor for the success of any treatment modality for infertility. It indicates a reduction in quantity and quality of oocytes in women of reproductive age group. It may be age related as seen in advanced years of reproductive life or may occur in young women due to diverse etiological factors. Evaluating ovarian reserve and individualizing the therapeutic strategies are very important for optimizing the success rate. Majority or women with POR need to undergo in vitro fertilization to achieve pregnancy. However, pregnancy rate remains low despite a plethora of interventions and is associated with high pregnancy loss. Early detection and active management are essential to minimize the need for egg donation in these women.

  4. Neoadjuvant chemotherapy as ovarian cancer treatment

    DEFF Research Database (Denmark)

    Fagö-Olsen, Carsten L; Ottesen, Bent; Kehlet, Henrik;

    2012-01-01

    INTRODUCTION: The traditional first-line treatment for patients with advanced ovarian cancer with primary debulking surgery (PDS) and adjuvant chemotherapy is controversial as some authors report a potential benefit from the alternative treatment with neoadjuvant chemotherapy (NACT) and interval...

  5. 金属硫蛋白与肿瘤增殖抗原在卵巢上皮性肿瘤组织中的表达及意义%Expressions of metallothionein and tumor proliferating antigen in epithelial ovarian carcinoma tissues and their significances

    Institute of Scientific and Technical Information of China (English)

    高迎春; 张爽

    2011-01-01

    目的:研究金属硫蛋白(MT)和肿瘤增殖抗原(Ki-67)在卵巢上皮性肿瘤组织中的表达及相关性和临床意义.方法:采用免疫纽化SP法及半定量分析法,检测105例卵巢上皮性肿瘤病理标本中的MT及Ki-67蛋白表达.结果:MT在卵巢癌及正常组织中表达有差异(P0.05);MT与Ki-67的表达强度恶性肿瘤高于正常、良性、交界性肿瘤(P<0.05),临床Ⅲ、Ⅳ期,病理2、3级的恶性肿瘤高于临床Ⅰ、Ⅱ期,病理1级者(P<0.01);MT与Ki-67的表达强度在恶性上皮性卵巢肿瘤中有显著相关性(P<0.05).结论:组织中MT、Ki-67的表达强度与卵巢肿瘤的性质有关.MT和Ki-67可能作为卵巢肿瘤的预后预测参考指标.%Objective: To study the expressions of metallothionein and tumor proliferating antigen ( Ki - 67 ) in epithelial ovarian carcinoma tissues, analyze their correlation and clinical significances. Methods: Immunohistochemical SP method and semi -quantitative analysis were used to detect the expressions of metallothionein and Ki - 67 protein in pathological samples of epithelial ovarian carcinoma. Results: There was significant difference in expression level of metallothionein between ovarian cancer and normal ovary (P < 0. 01 ), there was no significant difference in expression level of Ki -67 protein among ovarian carcinoma of different histological types ( P > 0. 05 ); the expression levels of metallothionein and Ki - 67 protein in malignant tumors were significantly higher than those in normal ovary,benign and borderline tumors (P <0. 05 ); the expression levels of metallothionein and Ki -67 protein in malignant tumors of clinical stage Ⅲ, Ⅳ, pathological grade 2, 3 were significantly higher than those in malignant tumors of clinical stage Ⅰ , Ⅱ, pathological grade Ⅰ; in malignant epithelial ovarian tumors, there was a significant correlation between metallothionein expression and Ki -67 protein expression (P <0. 05) . Conclusion: The

  6. Electron microscopy of the germ cells and the ovarian wall in Xiphinema (Nematoda).

    Science.gov (United States)

    Van de Velde, M C; Coomans, A

    1988-01-01

    The ovary of Xiphinema theresiae is studied ultrastructurally. It consists of two cell types, the ovarian epithelial cells and the germ cells. The ovarian epithelial cells form a thin layer around the germ cells. Their nuclei are located in between the germ cells. At some sites, processes of the ovarian epithelial cells migrate inward and form a central cytoplasmic mass. The germ cells have a large lobated nucleus, with an eccentric nucleolus, and are considered to represent young previtellogenic oocytes. In contact with the central cytoplasmic mass, the germ cells develop two membrane derived features, the villi and the small coated bulges, which most probably play a role in transport.

  7. Global Deletion of Trp53 Reverts Ovarian Tumor Phenotype of the Germ Cell–Deficient White Spotting Variant (Wv Mice

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    Kathy Qi Cai

    2015-01-01

    We tested if additional genetic mutation(s could convert the benign ovarian epithelial tumors to malignant tumors by crossing the Wv mutant into the Trp53 knockout background. Surprisingly, we found that global deletion of Trp53 suppressed the development of ovarian tubular adenomas in Wv mice. The ovaries of Wv/Wv; Trp53 (−/− mice were covered by a single layer of surface epithelium and lacked excessive epithelial proliferation. Rather, the ovaries contained a small number of follicles. The presence of ovarian follicles and granulosa cells, as indicated by Pgc7 and inhibin-alpha expression, correlated with the absence of epithelial lesions. A reduction of Pten gene dosage, as in Wv/Wv; Pten (+/− mice, produced a similar, though less dramatic, phenotype. We conclude that deletion of Trp53 prolongs the survival of ovarian follicles in Wv mice and consequently prevents the proliferation of ovarian epithelial cells and development of ovarian tubular adenomas. The results suggest that various cell types within the ovary communicate and mutually modulate, and an intact tissue environment is required to ensure homeostasis of ovarian surface epithelial cells. Especially, the current finding emphasizes the importance of ovarian follicles in suppressing the hyperplastic growth of ovarian epithelial cells, dominating over the loss of p53.

  8. Expression of IL-18, IL-18 Binding Protein, and IL-18 Receptor by Normal and Cancerous Human Ovarian Tissues: Possible Implication of IL-18 in the Pathogenesis of Ovarian Carcinoma

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    Liat Medina

    2014-01-01

    Full Text Available Proinflammatory cytokine IL-18 has been shown to be elevated in the sera of ovarian carcinoma patients. The aim of the study was to examine the levels and cellular origin of IL-18, IL-18 binding protein, and IL-18 receptor in normal and cancerous ovarian tissues. Ovarian tissue samples were examined by immunohistochemical staining for IL-18, IL-18BP, and IL-18R and mRNA of these cytokines was analyzed with semiquantitative PT-PCR. IL-18 levels were significantly higher in cancerous ovarian tissues (P=0.0007, IL-18BP levels were significantly higher in normal ovarian tissues (P=0.04, and the ratio of IL-18/IL-18BP was significantly higher in cancerous ovarian tissues (P=0.036. Cancerous ovarian tissues expressed significantly higher IL-18 mRNA levels (P=0.025, while there was no difference in the expression of IL-18BP mRNA and IL-18R mRNA between cancerous and normal ovarian tissues. IL-18 and IL-18BP were expressed dominantly in the epithelial cells of both cancerous and normal ovarian tissues, while IL-18R was expressed dominantly in the epithelial cells of cancerous ovarian tissues but expressed similarly in the epithelial and stromal cells of normal cancerous tissues. This study indicates a possible role of IL-18, IL-18BP, and IL-18R in the pathogenesis of epithelial ovarian carcinoma.

  9. [Cytostatic treatment of ovarian carcinoma].

    Science.gov (United States)

    Neijt, J P

    1999-10-30

    Shortly after treatment with the cytostatic combination of cisplatin and paclitaxel was generally accepted as the standard therapy for patients with epithelial ovarian carcinoma, many have come to regard the combination of carboplatin and paclitaxel as a better choice. The latter combination causes fewer side effects and may be used in the outpatient clinic. Conceivably, the carboplatin-paclitaxel scheme will shortly have to be adjusted again owing to results of current research. The intensive basic research of recent years, namely, is beginning to yield benefits for the therapeutic arsenal against ovarian carcinoma. Possibilities are inhibitors of the breakdown of extracellular matrix (such as marimastat) and inhibitors of signal transduction (such as trastuzumab). PMID:10578409

  10. Primary Ovarian Insufficiency

    Science.gov (United States)

    ... health/premature-ovarian-failure/DS00843 International Premature Ovarian Failure Association: www.ipofa.org ... to further patient education on hormone related issues. Network Sponsors The Hormone ...

  11. Increased expression of cysteine cathepsins in ovarian tissue from chickens with ovarian cancer

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    Ahn Suzie E

    2010-08-01

    Full Text Available Abstract Background Cysteine cathepsins (CTSs are involved in the degradation and remodeling of the extracellular matrix and are associated with cell transformation, differentiation, motility, and adhesion. These functions are also related to cancer cell invasion and metastasis. Chickens spontaneously develop epithelial ovarian cancer and are therefore a good animal model for human ovarian cancer. However, no studies have investigated the expression of CTSs in chickens with ovarian cancer. Methods Cancerous (n = 5 and normal (n = 3 ovaries were collected from 2-to 3-year-old hens, and ovarian tissue samples were collected for study. Ovarian cancers were evaluated with hematoxylin and eosin staining. Reverse transcriptase and quantitative PCR analyses, in situ hybridization analysis were performed to examine the mRNA expression pattern of three CTSs in detail, and protein expression of CTSB was evaluated. Results The CTSB, CTSC, and CTSS genes were highly expressed in cancerous chicken ovaries. Messenger RNAs for the three CTSs were localized to a nodule area, a major characteristic of cancerous ovaries, but the three CTSs showed no specific localization in normal ovaries. Immunoreactive CTSB protein was present in the nodule area of cancerous ovaries. Conclusion Our results suggest that CTSB, CTSC, and CTSS have important functions in the development of epithelial ovarian cancer.

  12. The relationship between serum levels of CA 125 and the degree of differentiation in ovarian neoplasms

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    Eduardo Cambruzzi

    2014-02-01

    Full Text Available Introduction: Primary ovarian neoplasms exhibit a wide range of histopathological aspects, and tumors with epithelial differentiation are the most frequent. Among the malignant tumors, the most common histological type corresponds to serous adenocarcinoma, whose diagnosis is established in advanced stages of the disease in approximately 75% of the patients. Tumor marker CA 125 represents a glycoprotein synthesized mainly by neoplastic cells with epithelial differentiation, and its serum level seems to be associated with the biological potential of these lesions. Objective: To estimate the association between serum levels of CA 125 and the degree of differentiation in primary ovarian neoplasms. Method: Sixty distinct cases of primary ovarian tumors were selected, previously analyzed at the Laboratory of Pathology of the Hospital Complex of Universidade Luterana do Brasil (Ulbra, between 2005 and 2010, from patients undergoing concomitant analysis of CA 125. In each case, age, tumor size, histological type, degree of differentiation, presence of necrosis and tumor invasion of the albuginea or extraovarian tissues, pathological stage and serum CA 125 were determined. Results: A statistically significant relationship between CA 125 levels and histological grade (p = 0.001, age (p = 0.009, biological behavior of the tumor (malignant or benign - p = 0.002 and extraovarian invasion (p = 0.005 was found. No relationship between CA 125 levels and tumor size (p = 0.1006 and pathologic stage (p = 0.1 was determined. Histologic grade was associated with the presence of necrosis (p = 0.001, extraovarian invasion (p = 0.009 and tumor size (p = 0.008. Conclusion: In the present study, serum levels of CA 125 were associated with histological grade in primary ovarian neoplasms, especially in high-grade malignant tumors, suggesting that high levels of this glycoprotein are associated with lesions of more aggressive biological behavior.

  13. 卵巢上皮性癌化疗途径对疗效和安全性影响的荟萃分析%Choose which method for the chemotherapy of epithelial ovarian carcinoma: a meta-analysis

    Institute of Scientific and Technical Information of China (English)

    崔瑛; 崔满华; 贾岩

    2010-01-01

    the six indicators of unpleasant chemotherapeutic effects (leucopenia, anemia, thrombopenia, GI tract reactions, neurotoxicity and fever), the occurrence of gastrointestinal reaetion increased. The difference was significant enough so that definite conclusions could be drawn. And the remaining five indicators had no statistical significance so that definite conclusions could not be drawn. Conclusions For patients with epithelial ovarian cancer ( Stages FIGO Ⅱ -Ⅳ ) undergoing previously a satisfactory tumor reduction surgery ( postoperative residual lesions < 1 to 2 cm), intraperitoneal chemotherapy can improve their 2 and 3-year PIS rates and the 2, 3 and 5-year OS rates; Intraperitoneal chemotherapy has not reduced the side effects. But there is an elevated occurrence of gastrointestinal reactions.

  14. 卵巢上皮性癌脐转移临床特征分析%Umbilicus metastasis in patients with epithelial ovarian cancer: clinical features of 21 patients

    Institute of Scientific and Technical Information of China (English)

    肖娟; 李俊东; 徐漫漫; 朱安娜; 冯艳玲

    2013-01-01

    目的 分析卵巢上皮性癌(EOC)脐转移的临床特点,探讨其发生率、诊断、治疗及预后相关因素.方法 回顾性分析1991年1月至2011年1月中山大学肿瘤防治中心收治的EOC患者2642例中经