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Sample records for advanced ovarian cancer

  1. 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...

  2. 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.

  3. 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

  4. 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...

  5. 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...

  6. 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

  7. 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

  8. 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)

  9. 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.

  10. 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 ...

  11. 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

  12. 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.

  13. 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...

  14. 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 ...

  15. 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

  16. 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

  17. Ovarian cancer and smoking

    DEFF Research Database (Denmark)

    Beral, V; Gaitskell, K; Hermon, C;

    2012-01-01

    Smoking has been linked to mucinous ovarian cancer, but its effects on other ovarian cancer subtypes and on overall ovarian cancer risk are unclear, and the findings from most studies with relevant data are unpublished. To assess these associations, we review the published and unpublished evidence....

  18. 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.

  19. 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

  20. 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...

  1. Ovarian Cancer Stage I

    Science.gov (United States)

    ... An inset shows cancer cells in the pelvic peritoneum. Also shown are the fallopian tubes, uterus, cervix, ... c) cancer cells are found in the pelvic peritoneum. Topics/Categories: Anatomy -- Gynecologic Cancer Types -- Ovarian Cancer ...

  2. 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

  3. 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.

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

    Directory of Open Access Journals (Sweden)

    Behtash Nadereh

    2010-02-01

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

  5. 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...

  6. 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.

  7. 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...

  8. 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...

  9. Ovarian Cancer Statistics

    Science.gov (United States)

    ... population data for older age groups are available. Statistics at a Glance Show More At a Glance ... with ovarian cancer in the United States. Survival Statistics Show More How Many People Survive 5 Years ...

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

    Directory of Open Access Journals (Sweden)

    Arash Rafii

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

  11. 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. 

  12. 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.

  13. Early Detection of Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Donna Badgwell

    2007-01-01

    Full Text Available Despite advances in therapy, ovarian cancer remains the most deadly of the gynecological cancers. Less than 30% of women with advanced stage disease survive long-term. When diagnosed in stage I, up to 90% of patients can be cured with conventional surgery and chemotherapy. At present, only 25% of ovarian cancers are detected in stage I due, in part, to the absence of specific symptoms and to lack of an effective screening strategy. Early detection of ovarian cancer might significantly improve the overall survival rate of women with ovarian cancer if 1 most cancers are clonal and unifocal, arising in the ovary rather than in the peritoneum, 2 metastatic disease results from progression of clinically detectable stage I lesions, and 3 cancers remain localized for a sufficient interval to permit cost-effective screening. Given the prevalence of ovarian cancer, strategies for early detection must have high sensitivity for early stage disease (> 75%, but must have extremely high specificity (99.6% to attain a positive predictive value of at least 10%. Transvaginal sonography (TVS, serum markers and a combination of the two modalities have been evaluated for early detection of ovarian cancer. Among the serum markers, CA125 has received the most attention, but lacks the sensitivity or specificity to function alone as a screening test. Greater specificity can be achieved by combining CA125 and TVS and/or by monitoring CA125 over time. Two stage screening strategies promise to be cost effective, where abnormal serum assays prompt TVS to detect lesions that require laparotomy. Accrual has been completed for a 200,000 woman trial in the United Kingdom that will test the ability of a rising CA125 to trigger TVS and subsequent exploratory surgery. Given the heterogeneity of ovarian cancer, it is unlikely that any single marker will be sufficiently sensitive to provide an effective initial screen. Sensitivity of serum assays might be enhanced by utilizing a

  14. 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

  15. Targeted Therapies in Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    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.

  16. Targeted Therapies in Epithelial Ovarian Cancer

    Energy Technology Data Exchange (ETDEWEB)

    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.

  17. National Ovarian Cancer Coalition

    Science.gov (United States)

    ... 10, 2016 TESARO, Inc., an oncology-focused biopharmaceutical company, and ENGOT, the European Network for Gynecological Oncological Trial groups, today announced the presentation ... Read More NOCC Launches NOCC CancerConnect Community Social Media Network for Women with Ovarian Cancer September ...

  18. 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...

  19. 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

  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. 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...

  2. Standardized FDG uptake as a prognostic variable and as a predictor of incomplete cytoreduction in primary advanced ovarian cancer

    DEFF Research Database (Denmark)

    Risum, Signe; Jakobsen, Annika Loft; Høgdall, Claus;

    2011-01-01

    Abstract Introduction. In patients with advanced ovarian cancer undergoing preoperative PET/CT, we investigated the prognostic value of SUV in the primary tumor and we evaluated the value of SUV for predicting incomplete primary cytoreduction (macroscopic residual tumor). Material and methods. From...... 15, 2009) the association between SUV and overall survival/cytoreductive result were analyzed in 60 ovarian cancer patients (58 stage III and two stage IV). Results. At inclusion median age was 62 years (range 35-85 years); 97% (58/60) had a performance status =2; 42% (25/60) underwent complete...... debulking (no macroscopic residual tumor); median SUV(max) was 13.5 (range 2.5-39.0). Median follow-up was 30.2 months. At follow-up 57% (34/60) were alive and 43% (26/60) had died from ovarian cancer. SUV(max) in patients alive was not statistically different from SUV(max) in dead patients (p=0...

  3. Other Gynecologic Cancers: endometrial, ovarian, vulvar and vaginal cancers

    OpenAIRE

    Duarte-Franco, Eliane; Franco, Eduardo L.

    2004-01-01

    Health issue In Canada, cancers of the endometrium, ovaries, vulva, vagina, placenta and adnexa account for 11% of all malignant neoplasms in women and 81% of all genital cancers. Although the incidence and mortality from vulvar and vaginal cancers are very low, endometrium and ovarian cancer are important public health problems. Key findings In Canada, there has been no appreciable improvement in survival for women with advanced endometrial (EC) or ovarian cancer (OC) over the past 30 years....

  4. Managing hereditary ovarian cancer

    NARCIS (Netherlands)

    Mourits, M. J.; de Bock, G. H.

    2009-01-01

    In this review we present an overview of recent developments in the management of hereditary ovarian cancer. Until recently, intensive screening of the ovaries was recommended to mutation carriers and their first-degree female relatives. However, since screening is not effective in detecting early-s

  5. [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.

  6. 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...

  7. Ovarian cancer screening in the general population.

    OpenAIRE

    Menon, U

    2007-01-01

    Despite significant improvements in therapy, ovarian cancer continues to be a leading cause of death amongst women with gynaecological malignancies. Advanced stage at diagnosis is thought to be a major contributor to mortality. Hence, there is considerable interest in early detection through screening. In the 1990s, Professor Jacobs pioneered the development of a multimodal ovarian cancer screening (OCS) strategy using serum CA125 as the first line screen and pelvic ultrasound as the second l...

  8. Rethinking ovarian cancer: recommendations for improving outcomes.

    Science.gov (United States)

    Vaughan, Sebastian; Coward, Jermaine I; Bast, Robert C; Berchuck, Andy; Berek, Jonathan S; Brenton, James D; Coukos, George; Crum, Christopher C; Drapkin, Ronny; Etemadmoghadam, Dariush; Friedlander, Michael; Gabra, Hani; Kaye, Stan B; Lord, Chris J; Lengyel, Ernst; Levine, Douglas A; McNeish, Iain A; Menon, Usha; Mills, Gordon B; Nephew, Kenneth P; Oza, Amit M; Sood, Anil K; Stronach, Euan A; Walczak, Henning; Bowtell, David D; Balkwill, Frances R

    2011-10-01

    There have been major advances in our understanding of the cellular and molecular biology of the human malignancies that are collectively referred to as ovarian cancer. At a recent Helene Harris Memorial Trust meeting, an international group of researchers considered actions that should be taken to improve the outcome for women with ovarian cancer. Nine major recommendations are outlined in this Opinion article. PMID:21941283

  9. 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.

  10. Current Research and Management of Ovarian Cancer in China

    Institute of Scientific and Technical Information of China (English)

    GUMeijiao; SHIWei

    2002-01-01

    Ovarian cancer is ne of the most lethal malignant tumors in China,represents the third most common cancer after cervical cancer and endometrial cancer,and the first leading cause of death from hynaecological cancers.Due to the lack of effective screening strategies and the absence of symptoms in early-stage of disease,over 70% of patients present at an advanced stage.Despite the advances in surgical techniques and conventional chemotheraphy,the prognosis of ovarian cancer has not been improved significantly,and indeed the long-term survival for patients with advanced disease does not exceed 20%.The aetiology of ovarian cancer temains poorly understood.In China,the major focus of research is to clarify the mechanism underlying ovarian cancer,develop more effective life-saving diagnostic and therapeutic measures,and undertake more population-based studies.This article summarizes current research,diagnosis and management of ovarian cancer in China.

  11. Diagnosis and Management of Ovarian Cancer.

    Science.gov (United States)

    Doubeni, Chyke A; Doubeni, Anna R; Myers, Allison E

    2016-06-01

    Ovarian cancer is the most lethal gynecologic cancer. Less than one-half of patients survive for more than five years after diagnosis. Ovarian cancer affects women of all ages but is most commonly diagnosed after menopause. More than 75% of affected women are diagnosed at an advanced stage because early-stage disease is usually asymptomatic and symptoms of late-stage disease are nonspecific. The strongest risk factors are advancing age and family history of ovarian and breast cancer. Women who have symptoms concerning for ovarian cancer should undergo a physical examination, transvaginal ultrasonography, and measurement of biomarkers such as cancer antigen 125. If results are suspicious for ovarian cancer, the patient should be referred to a gynecologic oncologist. Despite the low rate of early diagnosis, guidelines recommend against routine screening for ovarian cancer in average-risk women because screening, including routine pelvic examinations, is ineffective and associated with harm. However, a recent trial found a potential benefit of annual screening using an algorithm based on serial cancer antigen 125 measurements followed by transvaginal ultrasonography for women at increased risk, as determined by the algorithm. Women with an increased-risk family history should be referred for genetic counseling and, if genetic mutations (e.g., BRCA mutations) are identified, bilateral salpingo-oophorectomy can be considered for risk reduction. In both average- and high-risk women, long-term hormonal contraceptive use reduces risk by about 50%. The treatment of ovarian cancer usually involves surgery, with or without intraperitoneal and intravenous chemotherapy. Primary care physicians have important roles in posttreatment surveillance and end-of-life care. PMID:27281838

  12. 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.

  13. 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

  14. 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

  15. 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

  16. 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

  17. Imunotherapy opportunities in ovarian cancer

    Directory of Open Access Journals (Sweden)

    I. Zh. Shubina

    2013-01-01

    Full Text Available In the last decade, accumulated evidence in favor of that ovarian cancer is an immunogenic tumor. Immunotherapy is aimed at stimulating the innate and adaptive immunity, may cause an effective response in patients with ovarian cancer. Various approaches immunotherapy include cytokinetherapy, use of monoclonal antibodies and cell therapy.

  18. "Incessant ovulation" and ovarian cancer.

    Science.gov (United States)

    Casagrande, J T; Louie, E W; Pike, M C; Roy, S; Ross, R K; Henderson, B E

    1979-07-28

    A case-control study of 150 ovarian cancer patients under the age of 50 and individually matched controls was done to study the influence of fertility and oral contraceptive use on the risk of ovarian cancer. The risk decreased with increasing numbers of live births, with increasing numbers of incomplete pregnancies, and with the use of oral contraceptives. These three factors can be amalgamated into a single index of protection--"protected time"--by considering them all as periods of anovulation. The complement of protected time--viz., "ovulatory age", the period between menarche and diagnosis of ovarian cancer (or cessation of menses) minus "protected time"--was strongly related to risk of ovarian cancer. Other factors found to be associated with increased ovarian cancer risk were obesity, cervical polyps, and gallbladder disease. Women who had an "immediate" intolerance to oral contraceptive use had a fourfold increased risk of ovarian cancer. 7 patients, but no controls, could recall a family history of ovarian cancer. PMID:89281

  19. 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.

  20. 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.

  1. Antigen-specific active immunotherapy for ovarian cancer

    NARCIS (Netherlands)

    Leffers, N.; Daemen, T.; Helfrich, W.; Boezen, H. M.; Cohlen, B. J.; Melief, Cornelis; Nijman, H. W.

    2010-01-01

    BACKGROUND: Despite advances in chemotherapy, prognosis of ovarian cancer remains poor. Antigen-specific active immunotherapy aims to induce a tumour-antigen-specific anti-tumour immune responses as an alternative treatment for ovarian cancer. OBJECTIVES: To assess feasibility of antigen-specific ac

  2. 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.

  3. MicroRNAs and Recent Insights into Pediatric Ovarian Cancers

    Directory of Open Access Journals (Sweden)

    Jessica Anne Crawford

    2013-04-01

    Full Text Available Ovarian cancer is the most common pediatric gynecologic malignancy. When diag-nosed in children, ovarian cancers present unique challenges that differ dramatically from those faced by adults. Here, we review the spectrum of ovarian cancers found in young women and girls and discuss the biology of these diseases. A number of advances have re-cently shed significant new understanding on the potential causes of ovarian cancer in this unique population. Particular emphasis is placed on understanding how altered expression of non-coding RNA transcripts known as microRNAs play a key role in the etiology of ovarian germ cell and sex cord-stromal tumors. Emerging transgenic models for these diseases are also reviewed. Lastly, future challenges and opportunities for understanding pediatric ovarian cancers, delineating clinically useful biomarkers and developing targeted therapies are discussed.

  4. 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.

  5. 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.

  6. 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。

  7. Hormone therapy and ovarian cancer

    DEFF Research Database (Denmark)

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

    2009-01-01

    CONTEXT: Studies have suggested an increased risk of ovarian cancer among women taking postmenopausal hormone therapy. Data are sparse on the differential effects of formulations, regimens, and routes of administration. OBJECTIVE: To assess risk of ovarian cancer in perimenopausal and postmenopau......CONTEXT: Studies have suggested an increased risk of ovarian cancer among women taking postmenopausal hormone therapy. Data are sparse on the differential effects of formulations, regimens, and routes of administration. OBJECTIVE: To assess risk of ovarian cancer in perimenopausal...... and postmenopausal women receiving different hormone therapies. DESIGN AND SETTING: Nationwide prospective cohort study including all Danish women aged 50 through 79 years from 1995 through 2005 through individual linkage to Danish national registers. Redeemed prescription data from the National Register...... bands included hormone exposures as time-dependent covariates. PARTICIPANTS: A total of 909,946 women without hormone-sensitive cancer or bilateral oophorectomy. MAIN OUTCOME MEASURE: Ovarian cancer. RESULTS: In an average of 8.0 years of follow-up (7.3 million women-years), 3068 incident ovarian...

  8. Management of Ovarian Cancer in Elderly.

    Science.gov (United States)

    Giri, Sushil K; Nayak, Bhagyalaxmi

    2015-01-01

    As a result of increasing life expectancy, the cancer incidence in older population is on the rise. Ovarian cancer (OC) is predominantly the disease of elderly women. More than half of all OC occur in women older than 65 years. The incidence of the disease increases with the advancing age, peaking during 7(th) decade of life and remains elevated until the age of 80 years. With the changing demographic scenario the percentage of elderly patients is increasing and gynaecologic oncologists need to focus more on these patients and their specific needs. Due to their higher risk of morbidity and mortality compared to younger patients, elderly patients with advanced ovarian cancer are challenging to treat and are often treated less radically. Their outcome is impaired despite no consistent prognostic effect of age itself. To offer optimal radical management of the elderly women with ovarian cancer and to avoid suboptimal treatment, biological age and functional status need to be considered before individualized treatment plans are defined. Pretreatment assessment can be achieved by using different assessment tools. Patients can tolerate surgery and chemotherapy, as long as they are individually assessed for their medical, psychological, and functional capabilities before therapeutic intervention is initiated. Prospective trials involving elderly women with ovarian cancer are the need of the day to offer justified evidenced based optimal treatment for those who will be benefited from the treatment. PMID:26411955

  9. 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...

  10. 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

  11. 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

  12. 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

  13. Ovarian Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing ovarian cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  14. 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....

  15. 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.

  16. Do We Know What Causes Ovarian Cancer?

    Science.gov (United States)

    ... Next Topic Can ovarian cancer be prevented? Do we know what causes ovarian cancer? We don’t yet know exactly what causes most ovarian cancers. As discussed in the previous section, we do know some factors that make a woman ...

  17. 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

  18. 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...

  19. 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.

  20. 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...

  1. 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....

  2. Molecular imaging in ovarian cancer.

    Science.gov (United States)

    Reyners, A K L; Broekman, K E; Glaudemans, A W J M; Brouwers, A H; Arts, H J G; van der Zee, A G J; de Vries, E G E; Jalving, M

    2016-04-01

    Ovarian cancer has a high mortality and novel-targeted treatment strategies have not resulted in breakthroughs for this disease. Insight into the molecular characteristics of ovarian tumors may improve diagnosis and selection of patients for treatment with targeted therapies. A potential way to achieve this is by means of molecular imaging. Generic tumor processes, such as glucose metabolism ((18)F-fluorodeoxyglucose) and DNA synthesis ((18)F-fluorodeoxythymidine), can be visualized non-invasively. More specific targets, such as hormone receptors, growth factor receptors, growth factors and targets of immunotherapy, can also be visualized. Molecular imaging can capture data on intra-patient tumor heterogeneity and is of potential value for individualized, target-guided treatment selection. Early changes in molecular characteristics during therapy may serve as early predictors of response. In this review, we describe the current knowledge on molecular imaging in the diagnosis and as an upfront or early predictive biomarker in patients with ovarian cancer. PMID:27141066

  3. 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

  4. Hereditary breast and ovarian cancer

    DEFF Research Database (Denmark)

    Nielsen, Finn Cilius; van Overeem Hansen, Thomas; Sørensen, Claus Storgaard

    2016-01-01

    Genetic abnormalities in the DNA repair genes BRCA1 and BRCA2 predispose to hereditary breast and ovarian cancer (HBOC). However, only approximately 25% of cases of HBOC can be ascribed to BRCA1 and BRCA2 mutations. Recently, exome sequencing has uncovered substantial locus heterogeneity among...

  5. Ovarian cancer and body size

    DEFF Research Database (Denmark)

    Mosgaard, Berit Jul

    2012-01-01

    Only about half the studies that have collected information on the relevance of women's height and body mass index to their risk of developing ovarian cancer have published their results, and findings are inconsistent. Here, we bring together the worldwide evidence, published and unpublished, and...

  6. Exercise May Help Thwart Ovarian Cancer

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_159486.html Exercise May Help Thwart Ovarian Cancer Chronic inactivity linked ... TUESDAY, June 21, 2016 (HealthDay News) -- Lack of exercise is associated with an increased risk of ovarian ...

  7. Ovarian Cancer Stage II

    Science.gov (United States)

    ... primary peritoneal cancer) shows cancer in the pelvic peritoneum. Also shown are the cervix and vagina. In ... peritoneal cancer, cancer is found in the pelvic peritoneum and has not spread there from another part ...

  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. 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...

  10. Investigational Agents in Development for the Treatment of Ovarian Cancer

    OpenAIRE

    Westin, Shannon N.; Herzog, Thomas J.; Coleman, Robert L.

    2012-01-01

    Although significant success has been achieved in the treatment of advanced and recurrent ovarian cancer, there is clearly room for improvement. The use of targeted agents in this patient population has the promise to provide improved survival and quality of life. There are a myriad of relevant pathways under exploration in all settings of ovarian cancer. Clinical trial data are accumulating for antiangiogenic therapy, including vascular endothelial growth factor (VEGF)-specific inhibitors an...

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

    Directory of Open Access Journals (Sweden)

    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.

  12. Ovarian Cancer Pathogenesis: A Model in Evolution

    Directory of Open Access Journals (Sweden)

    Alison M. Karst

    2010-01-01

    Full Text Available Ovarian cancer is a deadly disease for which there is no effective means of early detection. Ovarian carcinomas comprise a diverse group of neoplasms, exhibiting a wide range of morphological characteristics, clinical manifestations, genetic alterations, and tumor behaviors. This high degree of heterogeneity presents a major clinical challenge in both diagnosing and treating ovarian cancer. Furthermore, the early events leading to ovarian carcinoma development are poorly understood, thus complicating efforts to develop screening modalities for this disease. Here, we provide an overview of the current models of ovarian cancer pathogenesis, highlighting recent findings implicating the fallopian tube fimbria as a possible site of origin of ovarian carcinomas. The ovarian cancer model will continue to evolve as we learn more about the genetics and etiology of this disease.

  13. Early Detection Biomarkers for Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Sreeja Sarojini

    2012-01-01

    Full Text Available Despite the widespread use of conventional and contemporary methods to detect ovarian cancer development, ovarian cancer remains a common and commonly fatal gynecological malignancy. The identification and validation of early detection biomarkers highly specific to ovarian cancer, which would permit development of minimally invasive screening methods for detecting early onset of the disease, are urgently needed. Current practices for early detection of ovarian cancer include transvaginal ultrasonography, biomarker analysis, or a combination of both. In this paper we review recent research on novel and robust biomarkers for early detection of ovarian cancer and provide specific details on their contributions to tumorigenesis. Promising biomarkers for early detection of ovarian cancer include KLK6/7, GSTT1, PRSS8, FOLR1, ALDH1, and miRNAs.

  14. 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...

  15. Ovarian failure due to cancer treatment and fertility preservation options

    Directory of Open Access Journals (Sweden)

    Soheila Aminimoghaddam

    2016-04-01

    Full Text Available Primary ovarian insufficiency (POI, commonly referred to premature ovarian failure, is defined as ovarian failure before the age of 40 years. It is the loss of ovarian function caused by a process directly affecting ovaries. Cancer therapy which includes surgery, radiotherapy, and chemotherapy influence ovarian function, leading to premature menopause and loss of fertility. POI is idiopathic in most cases (74-90%. The known causes, in addition to anticancer treatment, are other processes like chromosomal abnormalities, autoimmunity, and natural aging can result in secondary ovarian failure, which is detected by an increase in serum gonadotropin levels (FSH and LH. There are evident risks of POI in women treated for cancer. Those who receive anticancer treatments have an increased risk of developing POI. There by, anticancer drugs and radiation therapy are considered as the most common toxins of ovaries. Although cancer incidence rates in women less than 50 years old continue to increase during recent years, mortality rates are dramatically decreasing due to modern advances in treatment. Increasing numbers of survivors are now confronted with the long-term consequences of exposure to these treatments. The pool of primordial follicles in the ovary is fixed and any injury to the ovary can potentially reduce this ovarian reserve, effectively advancing the patient’s reproductive age, thus narrowing the window of reproductive opportunity. Ovarian failure occurs in a significant percentage of childhood cancer survivors and many of them will seek care for reproductive dysfunction. Nevertheless, Embryo cryopreservation, oocyte cryopreservation, ovary tissue cryopreservation, ovarian suppression and oophoro-pexy are some options to preserve fertility in these groups. As a result, having foreknowledge of potential treatment related ovarian failure will allow the physician to give a better counsel to patients and their family regarding the importance and

  16. 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.

  17. 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

  18. A Current Review of Targeted Therapeutics for Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Susana M. Campos

    2010-01-01

    Full Text Available Difficult to detect, ovarian cancer typically presents at an advanced stage. Significant progress has been achieved in the treatment of ovarian cancer with therapeutics focused on DNA replication or cell division. However, despite sensitivity to induction chemotherapy the majority of patients will develop recurrent disease. Conventional agents for recurrent disease offer little in terms of long-term responses. Various targeted therapeutics have been explored in the management of ovarian cancer. These include monoclonal antibodies to epidermal growth factor receptors, small molecule tyrosine kinase inhibitors, monoclonal antibodies directed at the vascular endothelial growth factor (bevacizumab, and the small tyrosine kinase inhibitors that target the vascular endothelial growth factor receptor. Recently, several other agents have come forth as potential therapeutic agents in the management of ovarian cancer. These include monoclonal antibodies to the folate receptor, triple angiokinase inhibitors, PARP inhibitors, aurora kinase inhibitors, inhibitors of the Hedgehog pathway, folate receptor antagonists, and MTOR inhibitors.

  19. Reliable in vitro studies require appropriate ovarian cancer cell lines.

    Science.gov (United States)

    Jacob, Francis; Nixdorf, Sheri; Hacker, Neville F; Heinzelmann-Schwarz, Viola A

    2014-01-01

    Ovarian cancer is the fifth most common cause of cancer death in women and the leading cause of death from gynaecological malignancies. Of the 75% women diagnosed with locally advanced or disseminated disease, only 30% will survive five years following treatment. This poor prognosis is due to the following reasons: limited understanding of the tumor origin, unclear initiating events and early developmental stages of ovarian cancer, lack of reliable ovarian cancer-specific biomarkers, and drug resistance in advanced cases. In the past, in vitro studies using cell line models have been an invaluable tool for basic, discovery-driven cancer research. However, numerous issues including misidentification and cross-contamination of cell lines have hindered research efforts. In this study we examined all ovarian cancer cell lines available from cell banks. Hereby, we identified inconsistencies in the reporting, difficulties in the identification of cell origin or clinical data of the donor patients, restricted ethnic and histological type representation, and a lack of tubal and peritoneal cancer cell lines. We recommend that all cell lines should be distributed via official cell banks only with strict guidelines regarding the minimal available information required to improve the quality of ovarian cancer research in future. PMID:24936210

  20. 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...

  1. What Is Ovarian Cancer?

    Science.gov (United States)

    ... a mix of more than a single subtype. Teratoma Teratomas are germ cell tumors with areas that, when ... cell tumor has a benign form called mature teratoma and a cancerous form called immature teratoma. The ...

  2. 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 fr...

  3. Ovarian cancer mortality and industrial pollution

    International Nuclear Information System (INIS)

    We investigated whether there might be excess ovarian cancer mortality among women residing near Spanish industries, according to different categories of industrial groups and toxic substances. An ecologic study was designed to examine ovarian cancer mortality at a municipal level (period 1997–2006). Population exposure to pollution was estimated by means of distance from town to facility. Using Poisson regression models, we assessed the relative risk of dying from ovarian cancer in zones around installations, and analyzed the effect of industrial groups and pollutant substances. Excess ovarian cancer mortality was detected in the vicinity of all sectors combined, and, principally, near refineries, fertilizers plants, glass production, paper production, food/beverage sector, waste treatment plants, pharmaceutical industry and ceramic. Insofar as substances were concerned, statistically significant associations were observed for installations releasing metals and polycyclic aromatic chemicals. These results support that residing near industries could be a risk factor for ovarian cancer mortality. - Highlights: • We studied excess mortality due to ovarian cancer near Spanish industries. • Integrated nested Laplace approximations were used as a Bayesian inference tool. • We found excess ovarian cancer mortality near all industrial groups as a whole. • Risk also was found in towns near industries releasing carcinogens and metals. • Risk was associated with plants releasing polycyclic aromatic chemicals and POPs. - Our results support that residing in the vicinity of pollutant industries could be a risk factor for ovarian cancer mortality

  4. Validating genetic risk associations for ovarian cancer through the international Ovarian Cancer Association Consortium

    DEFF Research Database (Denmark)

    Pearce, C L; Near, A M; Van Den Berg, D J;

    2009-01-01

    The search for genetic variants associated with ovarian cancer risk has focused on pathways including sex steroid hormones, DNA repair, and cell cycle control. The Ovarian Cancer Association Consortium (OCAC) identified 10 single-nucleotide polymorphisms (SNPs) in genes in these pathways, which had...... been genotyped by Consortium members and a pooled analysis of these data was conducted. Three of the 10 SNPs showed evidence of an association with ovarian cancer at P... and risk of ovarian cancer suggests that this pathway may be involved in ovarian carcinogenesis. Additional follow-up is warranted....

  5. The Role of MicroRNAs in Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Yasuto Kinose

    2014-01-01

    Full Text Available Ovarian cancer is the most lethal of malignant gynecological tumors. Its lethality may be due to difficulties in detecting it at an early stage and lack of effective treatments for patients with an advanced or recurrent status. Therefore, there is a strong need for prognostic and predictive markers to diagnose it early and to help optimize and personalize treatment. MicroRNAs are noncoding RNAs that regulate target genes posttranscriptionally. They are involved in carcinogenesis, cell cycle, apoptosis, proliferation, invasion, metastasis, and chemoresistance. The dysregulation of microRNAs is involved in the initiation and progression of human cancers including ovarian cancer, and strong evidence that microRNAs can act as oncogenes or tumor suppressor genes has emerged. Several microRNA signatures that are unique to ovarian cancer have been proposed, and serum-circulating microRNAs have the potential to be useful diagnostic and prognostic biomarkers. Various microRNAs such as those in the miR-200 family, the miR-199/214 cluster, or the let-7 paralogs have potential as therapeutic targets for disseminated or chemoresistant ovarian tumors. Although many obstacles need to be overcome, microRNA therapy could be a powerful tool for ovarian cancer prevention and treatment. In this review, we discuss the emerging roles of microRNAs in various aspects of ovarian cancer.

  6. Proteomics of ovarian cancer: functional insights and clinical applications

    Energy Technology Data Exchange (ETDEWEB)

    Elzek, Mohamed A.; Rodland, Karin D.

    2015-03-01

    In the past decade, there has been an increasing interest in applying proteomics to assist in understanding the pathogenesis of ovarian cancer, elucidating the mechanism of drug resistance, and in the development of biomarkers for early detection of ovarian cancer. Although ovarian cancer is a spectrum of different diseases, the strategies for diagnosis and treatment with surgery and adjuvant therapy are similar across ovarian cancer types, increasing the general applicabil- ity of discoveries made through proteomics research. While proteomic experiments face many difficulties which slow the pace of clinical applications, recent advances in proteomic technology contribute significantly to the identification of aberrant proteins and networks which can serve as targets for biomarker development and individualized therapies. This review provides a summary of the literature on proteomics’ contributions to ovarian cancer research and highlights the current issues, future directions, and challenges. We propose that protein-level characterization of primary lesion in ovarian cancer can decipher the mystery of this disease, improve diagnostic tools, and lead to more effective screening programs.

  7. Ovarian cancer mortality and industrial pollution.

    Science.gov (United States)

    García-Pérez, Javier; Lope, Virginia; López-Abente, Gonzalo; González-Sánchez, Mario; Fernández-Navarro, Pablo

    2015-10-01

    We investigated whether there might be excess ovarian cancer mortality among women residing near Spanish industries, according to different categories of industrial groups and toxic substances. An ecologic study was designed to examine ovarian cancer mortality at a municipal level (period 1997-2006). Population exposure to pollution was estimated by means of distance from town to facility. Using Poisson regression models, we assessed the relative risk of dying from ovarian cancer in zones around installations, and analyzed the effect of industrial groups and pollutant substances. Excess ovarian cancer mortality was detected in the vicinity of all sectors combined, and, principally, near refineries, fertilizers plants, glass production, paper production, food/beverage sector, waste treatment plants, pharmaceutical industry and ceramic. Insofar as substances were concerned, statistically significant associations were observed for installations releasing metals and polycyclic aromatic chemicals. These results support that residing near industries could be a risk factor for ovarian cancer mortality. PMID:26046426

  8. Predictive and therapeutic markers in ovarian cancer

    Science.gov (United States)

    Gray, Joe W.; Guan, Yinghui; Kuo, Wen-Lin; Fridlyand, Jane; Mills, Gordon B.

    2013-03-26

    Cancer markers may be developed to detect diseases characterized by increased expression of apoptosis-suppressing genes, such as aggressive cancers. Genes in the human chromosomal regions, 8q24, 11q13, 20q11-q13, were found to be amplified indicating in vivo drug resistance in diseases such as ovarian cancer. Diagnosis and assessment of amplification levels certain genes shown to be amplified, including PVT1, can be useful in prediction of poor outcome of patient's response and drug resistance in ovarian cancer patients with low survival rates. Certain genes were found to be high priority therapeutic targets by the identification of recurrent aberrations involving genome sequence, copy number and/or gene expression are associated with reduced survival duration in certain diseases and cancers, specifically ovarian cancer. Therapeutics to inhibit amplification and inhibitors of one of these genes, PVT1, target drug resistance in ovarian cancer patients with low survival rates is described.

  9. Other Gynecologic Cancers: endometrial, ovarian, vulvar and vaginal cancers.

    Science.gov (United States)

    Duarte-Franco, Eliane; Franco, Eduardo L

    2004-08-25

    HEALTH ISSUE: In Canada, cancers of the endometrium, ovaries, vulva, vagina, placenta and adnexa account for 11% of all malignant neoplasms in women and 81% of all genital cancers. Although the incidence and mortality from vulvar and vaginal cancers are very low, endometrium and ovarian cancer are important public health problems. KEY FINDINGS: In Canada, there has been no appreciable improvement in survival for women with advanced endometrial (EC) or ovarian cancer (OC) over the past 30 years. The prognosis of EC is good for most patients because diagnosis is made at early stages. However, survival of OC is poor; more than 70% of cases are diagnosed at late stages. Up to 10% of OCs is linked to familial aggregation. Cancers of the vulva and of the vagina are very rare. The survival experience for women with the latter is worse than for those with the former. Both share many risk factors with cervical cancer and the recent developments in the study of HPV infection should be applicable to these diseases as well. Of particular interest will be the advent of vaccines for the primary prevention of HPV infection. DATA GAPS AND RECOMMENDATIONS: At present, the best available means to diagnose gynecologic malignancies is a detailed clinical examination, considering the totality of information on potential and proven risk factors, such as age, reproductive health, sexual practices, use unopposed estrogens or of oral contraceptives or tubal ligation, obesity, diet, smoking, and the familial clustering of some of these cancers. PMID:15345077

  10. Stress-induced Phosphoprotein 1 as a Secreted Biomarker for Human Ovarian Cancer Promotes Cancer Cell Proliferation*

    OpenAIRE

    Wang, Tzu-Hao; Chao, Angel; Tsai, Chia-Lung; Chang, Chih-Long; Chen, Shun-Hua; Lee, Yun-Shien; Chen, Jen-Kun; Lin, Yi-Jun; Chang, Pi-Yueh; Wang, Chin-Jung; Chao, An-Shine; Chang, Shuenn-Dyh; Chang, Ting-Chang; Lai, Chyong-Huey; Wang, Hsin-Shih

    2010-01-01

    Ovarian cancers are frequently not diagnosed until advanced stages, resulting in a high case fatality rate. Because of this, more tumor markers, in addition to CA125, for detecting and monitoring ovarian cancer are needed. During a systematic search for potential biomarkers of ovarian cancer, we compared the protein profiles between tumor interstitial fluid and normal interstitial fluid of ovaries, rationalizing that abnormal levels of proteins in tumor interstitial fluid may be detected in p...

  11. 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...

  12. MiR-197 induces Taxol resistance in human ovarian cancer cells by regulating NLK.

    Science.gov (United States)

    Zou, Dongling; Wang, Dong; Li, Rong; Tang, Ying; Yuan, Li; Long, Xingtao; Zhou, Qi

    2015-09-01

    Chemotherapy is the preferred therapeutic approach for the therapy of advanced ovarian cancer, but 5-year survival rate remains low due to the development of drug resistance. Increasing evidence has documented that microRNAs (miRNAs) act important roles in drug resistance in a variety types of cancer. However, the roles of miRNA in regulating Taxol resistance in ovarian cancer and the detailed mechanism are less reported. We used Taqman probe stem loop real-time PCR to accurately measure the levels of miR-197 in normal ovarian cells, ovarian cancer cells, and Taxol-resistant ovarian cancer cells and found that miR-197 was significantly increased in Taxol-resistant ovarian cancer cells. Enforced expression of miR-197 can promote Taxol resistance, cell proliferation, and invasion of ovarian cancer cells. Meanwhile, repression of miR-197 in ovarian cancer cells can sensitize its response to Taxol and also induced attenuated cell proliferation and invasion ability. Furthermore, investigation of the detailed mechanism showed that the promotion of miR-197 on drug resistance in ovarian cancer cells was partially mediated by downregulating NLK, a negative regulator of WNT signaling pathway. Taken together, our work first demonstrated that miR-197 can confer drug resistance to Taxol, by regulating tumor suppressor, NLK expression in ovarian cancer cells.

  13. Repopulation of Ovarian Cancer Cells After Chemotherapy

    OpenAIRE

    Telleria, Carlos M.

    2013-01-01

    The high mortality rate caused by ovarian cancer has not changed for the past thirty years. Although most patients diagnosed with this disease respond to cytoreductive surgery and platinum-based chemotherapy and undergo remission, foci of cells almost always escape therapy, manage to survive, and acquire the capacity to repopulate the tumor. Repopulation of ovarian cancer cells that escape front-line chemotherapy, however, is a poorly understood phenomenon. Here I analyze cancer-initiating ce...

  14. HEALTHY EATING INDEX AND OVARIAN CANCER RISK

    OpenAIRE

    Chandran, Urmila; Elisa V Bandera; Williams-King, Melony G.; Paddock, Lisa E.; Rodriguez-Rodriguez, Lorna; Lu, Shou-En; Faulkner, Shameka; Pulick, Katherine; Olson, Sara H.

    2011-01-01

    The evidence for a role of diet on ovarian cancer prevention remains inconclusive. While many studies have evaluated individual foods and food groups, the evaluation of a comprehensive dietary quality index for predicting cancer risk has received little attention. This study investigates the association between the Healthy Eating Index (HEI), which reflects adherence to the current USDA Dietary Guidelines for Americans, and ovarian cancer risk in a population-based case-control study in New J...

  15. Oncolytic reovirus against ovarian and colon cancer.

    Science.gov (United States)

    Hirasawa, Kensuke; Nishikawa, Sandra G; Norman, Kara L; Alain, Tommy; Kossakowska, Anna; Lee, Patrick W K

    2002-03-15

    Reovirus selectively replicates in and destroys cancer cells with an activated Ras signaling pathway. In this study, we evaluated the feasibility of using reovirus (serotype 3, strain Dearing) as an antihuman colon and ovarian cancer agent. In in vitro studies, reovirus infection in human colon and ovarian cell lines was assessed by cytopathic effect as detected by light microscopy, [(35)S]Methionine labeling of infected cells for viral protein synthesis and progeny virus production by plaque assay. We observed that reovirus efficiently infected all five human colon cancer cell lines (Caco-2, DLD-1, HCT-116, HT-29, and SW48) and four human ovarian cancer cell lines (MDAH2774, PA-1, SKOV3, and SW626) which were tested, but not a normal colon cell line (CCD-18Co) or a normal ovarian cell line (NOV-31). We also observed that the Ras activity in the human colon and ovarian cancer cell lines was elevated compared with that in normal colon and ovarian cell lines. In animal models, intraneoplastic as well as i.v. inoculation of reovirus resulted in significant regression of established s.c. human colon and ovarian tumors implanted at the hind flank. Histological studies revealed that reovirus infection in vivo was restricted to tumor cells, whereas the surrounding normal tissue remained uninfected. Additionally, in an i.p. human ovarian cancer xenograft model, inhibition of ascites tumor formation and the survival of animals treated with live reovirus was significantly greater than of control mice treated with UV-inactivated reovirus. Reovirus infection in ex vivo primary human ovarian tumor surgical samples was also confirmed, further demonstrating the potential of reovirus therapy. These results suggest that reovirus holds promise as a novel agent for human colon and ovarian cancer therapy. PMID:11912142

  16. Accumulation and toxicity of antibody-targeted doxorubicin-loaded PEG-PE micelles in ovarian cancer cell spheroid model

    OpenAIRE

    Perche, Federico; Torchilin, Vladimir P.

    2012-01-01

    We describe the evaluation of doxorubicin-loaded PEG-PE micelles targeting using an ovarian cancer cell spheroid model. Most ovarian cancer patients present at an advanced clinical stage and develop resistance to standard of care platinum/taxane therapy. Doxorubicin is also approved for ovarian cancer but had limited benefits in refractory patients. In this study, we used drug-resistant spheroid cultures of ovarian carcinoma to evaluate the uptake and cytotoxicity of an antibody-targeted doxo...

  17. Rethinking ovarian cancer II: reducing mortality from high-grade serous ovarian cancer.

    Science.gov (United States)

    Bowtell, David D; Böhm, Steffen; Ahmed, Ahmed A; Aspuria, Paul-Joseph; Bast, Robert C; Beral, Valerie; Berek, Jonathan S; Birrer, Michael J; Blagden, Sarah; Bookman, Michael A; Brenton, James D; Chiappinelli, Katherine B; Martins, Filipe Correia; Coukos, George; Drapkin, Ronny; Edmondson, Richard; Fotopoulou, Christina; Gabra, Hani; Galon, Jérôme; Gourley, Charlie; Heong, Valerie; Huntsman, David G; Iwanicki, Marcin; Karlan, Beth Y; Kaye, Allyson; Lengyel, Ernst; Levine, Douglas A; Lu, Karen H; McNeish, Iain A; Menon, Usha; Narod, Steven A; Nelson, Brad H; Nephew, Kenneth P; Pharoah, Paul; Powell, Daniel J; Ramos, Pilar; Romero, Iris L; Scott, Clare L; Sood, Anil K; Stronach, Euan A; Balkwill, Frances R

    2015-11-01

    High-grade serous ovarian cancer (HGSOC) accounts for 70-80% of ovarian cancer deaths, and overall survival has not changed significantly for several decades. In this Opinion article, we outline a set of research priorities that we believe will reduce incidence and improve outcomes for women with this disease. This 'roadmap' for HGSOC was determined after extensive discussions at an Ovarian Cancer Action meeting in January 2015. PMID:26493647

  18. 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

  19. Genetic profiles distinguish different types of hereditary ovarian cancer

    DEFF Research Database (Denmark)

    Domanska, Katarina; Malander, Susanne; Staaf, Johan;

    2010-01-01

    Heredity represents the strongest risk factor for ovarian cancer with disease predisposing mutations identified in 15% of the tumors. With the aim to identify genetic classifiers for hereditary ovarian cancer, we profiled hereditary ovarian cancers linked to the hereditary breast and ovarian canc...

  20. 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....

  1. Obesity and risk of ovarian cancer subtypes

    DEFF Research Database (Denmark)

    Olsen, Catherine M; Nagle, Christina M; Whiteman, David C;

    2013-01-01

    Whilst previous studies have reported that higher BMI increases a woman's risk of developing ovarian cancer, associations for the different histological subtypes have not been well defined. As the prevalence of obesity has increased dramatically, and classification of ovarian histology has improv......, it does not increase risk of high-grade invasive serous cancers, and reducing BMI is therefore unlikely to prevent the majority of ovarian cancer deaths. Other modifiable factors must be identified to control this disease.......Whilst previous studies have reported that higher BMI increases a woman's risk of developing ovarian cancer, associations for the different histological subtypes have not been well defined. As the prevalence of obesity has increased dramatically, and classification of ovarian histology has improved...... in the last decade, we sought to examine the association in a pooled analysis of recent studies participating in the Ovarian Cancer Association Consortium. We evaluated the association between BMI (recent, maximum and in young adulthood) and ovarian cancer risk using original data from 15 case...

  2. 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

  3. 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....

  4. 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

  5. Ovarian cancer in an interdisciplinary context

    DEFF Research Database (Denmark)

    Seibæk, Lene

      Introduction Worldwide, ovarian cancer is the sixth most common type of cancer, with more than 200,000 new cases each year and 125,000 related deaths. During the last decade, centralization and standardisation of surgical treatment have proven to be important tools in ovarian cancer to improve...... quality and survival. However, treatment efforts must be combined with high quality care, psychosocial support and organisational improvements.   Objectives The aim of this study was to evaluate an optimal debulking surgery programme in ovarian cancer, and subsequently develop a method of monitoring...... care resources and in future research. By using the interdisciplinary approach, women with ovarian cancer can benefit from a coherent and collaborative health care system.  ...

  6. 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....

  7. 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...

  8. Ormeloxifene efficiently inhibits ovarian cancer growth

    Science.gov (United States)

    Maher, Diane M.; Khan, Sheema; Nordquist, Jordan; Ebeling, Mara C.; Bauer, Nichole A.; Kopel, Lucas; Singh, Man Mohan; Halaweish, Fathi; Bell, Maria C.; Jaggi, Meena; Chauhan, Subhash C.

    2014-01-01

    Ovarian cancer continues to be a leading cause of cancer related deaths for women. Anticancer agents effective against chemo-resistant cells are greatly needed for ovarian cancer treatment. Repurposing drugs currently in human use is an attractive strategy for developing novel cancer treatments with expedited translation into clinical trials. Therefore, we examined whether ormeloxifene (ORM), a non-steroidal Selective Estrogen Receptor Modulator (SERM) currently used for contraception, is therapeutically effective at inhibiting ovarian cancer growth. We report that ORM treatment inhibits cell growth and induces apoptosis in ovarian cancer cell lines, including cell lines resistant to cisplatin. Furthermore, ORM treatment decreases Akt phosphorylation, increases p53 phosphorylation, and modulates the expression and localization patterns of p27, cyclin E, cyclin D1, and CDK2. In a pre-clinical xenograft mouse ORM treatment significantly reduces tumorigenesis and metastasis. These results indicate that ORM effectively inhibits the growth of cisplatin resistant ovarian cancer cells. ORM is currently in human use and has an established record of patient safety. Our encouraging in vitro and pre-clinical in vivo findings indicate that ORM is a promising candidate for the treatment of ovarian cancer. PMID:25306892

  9. Ovarian cancer after in vitro fertilization

    Directory of Open Access Journals (Sweden)

    Milenković Vera

    2004-01-01

    Full Text Available There is serious concern about cancer risk in women undergoing ovarian stimulation treatment for infertility and long-term safety of these procedures. Association between fertility drugs and ovarian cancer is still controversial. A 30-year-old woman was referred to our institution with the initial diagnosis of an adnexal tumor after in vitro fertilization. Her history revealed adnexectomy for mucinous cystadenofibroma of the left ovary eight years ago, and cystectomy due to cystadenoma of the right ovary three years ago. At admission, the most remarkable findings were high temperature and elevated white blood cell count and erythrocyte sedimentation rate. Broad spectrum antibiotic treatment was initiated. Six days after admission, the patient was feverish, with temperature up to 38°C, and evident signs of the acute abdomen. Immediate laparotomy was performed and multilocular right adnexal tumor 150x130x100 millimeters in size was identified. The right salpingo-oophorectomy was carried out. Pathological diagnosis was mucinous ovarian adenocarcinoma. Eighteen days later, radical surgery was performed. After the surgery, chemotherapy was applied. There is an urgent need for clear interpretation of the association between fertility drugs and subsequent higher ovarian cancer risk. Lacking conclusive evidence, an increased risk of ovarian cancer has been reported and more recently disputed. Higher ovarian cancer risk may be serious and even life-threatening complication for women undergoing ovarian stimulation.

  10. 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.

  11. 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

  12. 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.

  13. 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...

  14. Ovarian cancer after in vitro fertilization

    OpenAIRE

    Milenković Vera; Sparić Radmila; Dokić Milan D.; Petković Spasoje; Atanacković Jasmina

    2004-01-01

    There is serious concern about cancer risk in women undergoing ovarian stimulation treatment for infertility and long-term safety of these procedures. Association between fertility drugs and ovarian cancer is still controversial. A 30-year-old woman was referred to our institution with the initial diagnosis of an adnexal tumor after in vitro fertilization. Her history revealed adnexectomy for mucinous cystadenofibroma of the left ovary eight years ago, and cystectomy due to cystadenoma of the...

  15. Immunotherapy of Ovarian Cancer: The Role of Checkpoint Inhibitors

    Directory of Open Access Journals (Sweden)

    Francesca De Felice

    2015-01-01

    Full Text Available Ovarian cancer is the most important cause of gynecological cancer-related mortality, with the majority of women presenting with advanced disease. Although surgery and chemotherapy can improve survival rates, it is necessary to integrate alternative strategies to improve the outcomes. Advances in understanding the role of immune system in the pathogenesis of cancer have led to the rapid evolvement of immunotherapy, which might establish a sustained immune system response against recurring cancer cells. Recently, it has emerged that powerful immunologic effector cells may be blocked by inhibitory regulatory pathways controlled by specific molecules often called “immune checkpoints,” which turn off the immune system. Similarly, cancer cells are able to use these checkpoints to avoid immune control and rejection. Inhibition of these inhibitory pathways represents a potent strategy in the fight against cancer and is currently under investigation with encouraging results in some cancers, such as melanoma. In ovarian cancer researches are still in an early phase, but with promising results. In this review we will explore the rationale of immunotherapy in ovarian cancer with a special focus on these emerging molecules.

  16. Unbalanced estrogen metabolism in ovarian cancer.

    Science.gov (United States)

    Zahid, Muhammad; Beseler, Cheryl L; Hall, James B; LeVan, Tricia; Cavalieri, Ercole L; Rogan, Eleanor G

    2014-05-15

    Greater exposure to estrogens is a risk factor for ovarian cancer. To investigate the role of estrogens in ovarian cancer, a spot urine sample and a saliva sample were obtained from 33 women with ovarian cancer and 34 age-matched controls. Thirty-eight estrogen metabolites, conjugates and DNA adducts were analyzed in the urine samples using ultraperformance liquid chromatography/tandem mass spectrometry, and the ratio of adducts to metabolites and conjugates was calculated for each sample. The ratio of depurinating estrogen-DNA adducts to estrogen metabolites and conjugates was significantly higher in cases compared to controls (p < 0.0001), demonstrating high specificity and sensitivity. DNA was purified from the saliva samples and analyzed for genetic polymorphisms in the genes for two estrogen-metabolizing enzymes. Women with two low-activity alleles of catechol-O-methyltransferase plus one or two high-activity alleles of cytochrome P450 1B1 had higher levels of estrogen-DNA adducts and were more likely to have ovarian cancer. These findings indicate that estrogen metabolism is unbalanced in ovarian cancer and suggest that formation of estrogen-DNA adducts plays a critical role in the initiation of ovarian cancer. PMID:24170413

  17. 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.

  18. Obesity and risk of ovarian cancer subtypes: evidence from the Ovarian Cancer Association Consortium

    OpenAIRE

    Olsen, C. M.; Nagle, C. M.; Whiteman, D C; Ness, R; C. L. Pearce; Pike, M. C.; Rossing, M A; Terry, Kathryn Lynne; Wu, A. H.; Risch, H A; Yu, H.; Doherty, J. A.; Chang-Claude, J; Hein, R.; Nickels, S

    2013-01-01

    Whilst previous studies have reported that higher body-mass index (BMI) increases a woman’s risk of developing ovarian cancer, associations for the different histological subtypes have not been well defined. As the prevalence of obesity has increased dramatically, and classification of ovarian histology has improved in the last decade, we sought to examine the association in a pooled analysis of recent studies participating in the Ovarian Cancer Association Consortium. We ev...

  19. Identification of BRCA1-deficient ovarian cancers

    DEFF Research Database (Denmark)

    Skytte, Anne-Bine; Waldstrøm, Marianne; Rasmussen, Anders Aamann;

    2011-01-01

    . Design. BRCA1-immunohistochemistry (IHC), fluorescence in-situ hybridization (FISH) and methylation analyses were performed on formalin-fixed, paraffin-embedded ovarian cancer tissue. Sample: 54 ovarian cancers; 15 BRCA1 cancers, 4 BRCA2 cancers, 10 cancers from patients with a family history...... but no mutation detected, and 25 ovarian cancers with unknown BRCA1 status. Results. Abnormal BRCA1 IHC was found to indicate BRCA mutations with a sensitivity of 80%, a specificity of 93%, and an estimated positive predictive value of 73%. FISH analyses supported the diagnosis in most cases. Methylation analyses...... could indicate BRCA deficiency in combination with one of the other methods. Conclusions. BRCA1 IHC is a promising screening method for BRCA1 mutation detection....

  20. Curcumin induces chemo/radio-sensitization in ovarian cancer cells and curcumin nanoparticles inhibit ovarian cancer cell growth

    Directory of Open Access Journals (Sweden)

    Yallapu Murali M

    2010-04-01

    Full Text Available Abstract Background Chemo/radio-resistance is a major obstacle in treating advanced ovarian cancer. The efficacy of current treatments may be improved by increasing the sensitivity of cancer cells to chemo/radiation therapies. Curcumin is a naturally occurring compound with anti-cancer activity in multiple cancers; however, its chemo/radio-sensitizing potential is not well studied in ovarian cancer. Herein, we demonstrate the effectiveness of a curcumin pre-treatment strategy for chemo/radio-sensitizing cisplatin resistant ovarian cancer cells. To improve the efficacy and specificity of curcumin induced chemo/radio sensitization, we developed a curcumin nanoparticle formulation conjugated with a monoclonal antibody specific for cancer cells. Methods Cisplatin resistant A2780CP ovarian cancer cells were pre-treated with curcumin followed by exposure to cisplatin or radiation and the effect on cell growth was determined by MTS and colony formation assays. The effect of curcumin pre-treatment on the expression of apoptosis related proteins and β-catenin was determined by Western blotting or Flow Cytometry. A luciferase reporter assay was used to determine the effect of curcumin on β-catenin transcription activity. The poly(lactic acid-co-glycolic acid (PLGA nanoparticle formulation of curcumin (Nano-CUR was developed by a modified nano-precipitation method and physico-chemical characterization was performed by transmission electron microscopy and dynamic light scattering methods. Results Curcumin pre-treatment considerably reduced the dose of cisplatin and radiation required to inhibit the growth of cisplatin resistant ovarian cancer cells. During the 6 hr pre-treatment, curcumin down regulated the expression of Bcl-XL and Mcl-1 pro-survival proteins. Curcumin pre-treatment followed by exposure to low doses of cisplatin increased apoptosis as indicated by annexin V staining and cleavage of caspase 9 and PARP. Additionally, curcumin pre

  1. 77 FR 55095 - National Ovarian Cancer Awareness Month, 2012

    Science.gov (United States)

    2012-09-06

    ..., who have a family history of ovarian or breast cancer, or who have had certain cancers in the past are... Documents#0;#0; ] Proclamation 8853 of August 31, 2012 National Ovarian Cancer Awareness Month, 2012 By the... their lives to ovarian cancer. They are mothers and daughters, sisters and grandmothers,...

  2. Quality of life of advanced ovarian cancer patients in the randomized phase III study comparing primary debulking surgery versus neo-adjuvant chemotherapy

    NARCIS (Netherlands)

    Greimel, E.; Kristensen, G.B.; Burg, M.E.L. van der; Coronado, P.; Rustin, G.; Rio, A.S. del; Reed, N.S.; Nordal, R.R.; Coens, C.; Vergote, I.; Massuger, L.F.A.G.; Ottevanger, P.B.

    2013-01-01

    OBJECTIVE: The EORTC 55971 trial compared primary debulking surgery (PDS) versus neo-adjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS). The impact of both treatment arms on quality of life (QOL) is reported. METHODS: Patients with stages IIIc or IV ovarian cancer completed th

  3. Ovarian stimulation in patients with breast cancer.

    Science.gov (United States)

    Muñoz, Elkin; González, Naira; Muñoz, Luis; Aguilar, Jesús; Velasco, Juan A García

    2015-01-01

    Breast cancer is the most prevalent malignancy among women under 50. Improvements in diagnosis and treatment have yielded an important decrease in mortality in the last 20 years. In many cases, chemotherapy and radiotherapy develop side effects on the reproductive function. Therefore, before the anti-cancer treatment impairs fertility, clinicians should offer some techniques for fertility preservation for women planning motherhood in the future. In order to obtain more available oocytes for IVF, the ovary must be stimulated. New protocols which prevent exposure to increased estrogen during gonadotropin stimulation, measurements to avoid the delay in starting anti-cancer treatment or the outcome of ovarian stimulation have been addressed in this review. There is no evidence of association between ovarian stimulation and breast cancer. It seems that there are more relevant other confluent factors than ovarian stimulation. Factors that can modify the risk of breast cancer include: parity, age at full-term birth, age of menarche, and family history. There is an association between breast cancer and exogenous estrogen. Therefore, specific protocols to stimulate patients with breast cancer include anti-estrogen agents such as letrozole. By using letrozole plus recombinant follicular stimulating hormone, patients develop a multifollicular growth with only a mild increase in estradiol serum levels. Controlled ovarian stimulation (COS) takes around 10 days, and we discuss new strategies to start COS as soon as possible. Protocols starting during the luteal phase or after inducing the menses currently prevent a delay in starting ovarian stimulation. Patients with breast cancer have a poorer response to COS compared with patients without cancer who are stimulated with conventional protocols of gonadotropins. Although many centres offer fertility preservation and many patients undergo ovarian stimulation, there are not enough studies to evaluate the recurrence, breast cancer

  4. 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

  5. The relation between endometriosis and ovarian cancer - a review

    DEFF Research Database (Denmark)

    Heidemann, Lene Nyhøj; Hartwell, Dorthe; Heidemann, Christian Hamilton;

    2014-01-01

    Endometriosis is known to harbor characteristics substantiating that it is a possible precursor of ovarian cancer.......Endometriosis is known to harbor characteristics substantiating that it is a possible precursor of ovarian cancer....

  6. Molecular biomarker set for early detection of ovarian cancer

    KAUST Repository

    Bajic, Vladimir B.

    2015-06-16

    Embodiments of the present invention concern methods and compositions related to detection of ovarian cancer, including detection of the stage of ovarian cancer, in some cases. In particular, the invention encompasses use of expression of TFAP2A and in some embodiments CA125 and/or E2F5 to identify ovarian cancer, including detecting mRNA and/or protein levels of the respective gene products. Kits for detection of ovarian cancer are also described.

  7. Use of analgesic drugs and risk of ovarian cancer

    DEFF Research Database (Denmark)

    Ammundsen, Henriette B; Faber, Mette T; Jensen, Allan;

    2012-01-01

    The role of analgesic drug use in development of ovarian cancer is not fully understood. We examined the association between analgesic use and risk of ovarian cancer. In addition, we examined whether the association differed according to histological types.......The role of analgesic drug use in development of ovarian cancer is not fully understood. We examined the association between analgesic use and risk of ovarian cancer. In addition, we examined whether the association differed according to histological types....

  8. Expression of Cyclooxygenase-2 in Ovarian Cancer Cell Lines

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    To investigate the expression of cyclooxygenase-2 (COX-2) in ovarian cancer cell lines,RT-PCR and immunocytochemistry were used to detect the expression of COX-2 in 5 ovarian cancer cell lines. The expression of COX-2 mRNA and protein was detected in all 5 cell lines. It is suggested that COX-2 is expressed in ovarian cancer cell lines, which provides a basis for the chemoprevention of ovarian cancer.

  9. 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

  10. Possible pathogenetic types of sporadical ovarian cancer

    Directory of Open Access Journals (Sweden)

    L. A. Ashrafyan

    2012-01-01

    Full Text Available This article in question dwells on a possible pathogenetic model ovarian cancer, it’s histogenesis speciality, the role of ovulation, chronic in- flammation and stem cells. The scheme of two variant of avarian cancer progress and possible ways of prevention it are represented as well.

  11. Neoadjuvant chemotherapy as ovarian cancer treatment: ever more used with major regional differences

    DEFF Research Database (Denmark)

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

    2012-01-01

    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 debulking...

  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

    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.

  13. Hedgehog signaling pathway and ovarian cancer

    Institute of Scientific and Technical Information of China (English)

    Qi Chen; Guolan Gao; Shiwen Luo

    2013-01-01

    Epithelial ovarian carcinoma (EOC) is the most common form of ovarian malignancies and the most lethal gynecologic malignancy in the United States.To date,in spite of treatment to it with the extensive surgical debulking and chemotherapy,the prognosis of EOC remains dismal.Recently,it has become increasingly clear that in many instances,the signaling and molecular players that control development are the same,and when inappropriately regulated,drive tumorigenesis and cancer development.Here,we discuss the possible involvement of Hedgehog (Hh) pathway in the cellular regulation and development of cancer in the ovaries.Using the in vitro and in vivo assays developed has facilitated the dissection of the mechanisms behind Hh-driven ovarian cancers formation and growth.Based on recent studies,we propose that the inhibition of Hh signaling may interfere with spheroid-like structures in ovarian cancers.The components of the Hh signaling may provide novel drug targets,which could be explored as crucial combinatorial strategies for the treatment of ovarian cancers.

  14. 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

  15. Clinical significance of plasma lysophosphatidic acid levels in the differential diagnosis of ovarian cancer

    Directory of Open Access Journals (Sweden)

    Yun-Jie Zhang

    2015-01-01

    Full Text Available Objective: To investigate the value of lysophosphatidic acid (LPA in the diagnosis of ovarian cancer. Materials and Methods: We first performed a hospital-based, case-control study involving 123 ovarian cancer patients and 101 benign ovarian tumor patients, and then conducted a meta-analysis with 19 case-control studies to assess the correlation between ovarian cancer and plasma LPA levels. Results: The case-control study results demonstrated that ovarian cancer patients have increased LPA and cancer antigen (CA-125 levels compared to patients with benign ovarian tumor (LPA: Ovarian cancer vs benign ovarian tumor: 5.28 ± 1.52 vs 1.82 ± 0.77 μmol/L; CA-125: Ovarian cancer vs benign ovarian tumor: 87.17 ± 45.81 vs. 14.03 ± 10.14 U/mL, which showed statistically significant differences (both P < 0.05. LPA with advanced sensitivity, specificity, positive predictive value, negative predictive value, and accuracy rate of diagnosis excelled CA-125 in the diagnosis of ovarian cancer (both P < 0.05. The areas under the receiver operating characteristic (ROC curve in the diagnosis of ovarian cancer (LPA: 0.983; CA-125: 0.910 were statistically significant compared with the reference (both P < 0.001 and the difference of the areas of ROC curve between LPA and CA-125 in the diagnosis of ovarian cancer showed statistically significant difference (P < 0.05. The meta-analysis results suggested that plasma LPA levels were higher in ovarian cancer tissues than in benign tissues (standardized mean difference (SMD =2.36, 95% confidence interval (CI: 1.61-3.11, P < 0.001 and normal tissues (SMD = 2.32, 95% CI: 1.77-2.87, P < 0.001. Conclusion: LPA shows greater value in the diagnosis of ovarian cancer compared to CA-125 and may be employed as a biological index to diagnose ovarian cancer.

  16. Menopausal hormone use and ovarian cancer risk

    DEFF Research Database (Denmark)

    Beral, V; Gaitskell, K; Hermon, C;

    2015-01-01

    BACKGROUND: Half the epidemiological studies with information about menopausal hormone therapy and ovarian cancer risk remain unpublished, and some retrospective studies could have been biased by selective participation or recall. We aimed to assess with minimal bias the effects of hormone therapy...... on ovarian cancer risk. METHODS: Individual participant datasets from 52 epidemiological studies were analysed centrally. The principal analyses involved the prospective studies (with last hormone therapy use extrapolated forwards for up to 4 years). Sensitivity analyses included the retrospective studies....... Adjusted Poisson regressions yielded relative risks (RRs) versus never-use. FINDINGS: During prospective follow-up, 12 110 postmenopausal women, 55% (6601) of whom had used hormone therapy, developed ovarian cancer. Among women last recorded as current users, risk was increased even with

  17. Breast cancer susceptibility variants alter risk in familial ovarian cancer.

    Science.gov (United States)

    Latif, A; McBurney, H J; Roberts, S A; Lalloo, F; Howell, A; Evans, D G; Newman, W G

    2010-12-01

    Recent candidate gene and genome wide association studies have revealed novel loci associated with an increased risk of breast cancer. We evaluated the effect of these breast cancer associated variants on ovarian cancer risk in individuals with familial ovarian cancer both with and without BRCA1 or BRCA2 mutations. A total of 158 unrelated white British women (54 BRCA1/2 mutation positive and 104 BRCA1/2 mutation negative) with familial ovarian cancer were genotyped for FGFR2, TNRC9/TOX3 and CASP8 variants. The p.Asp302His CASP8 variant was associated with reduced ovarian cancer risk in the familial BRCA1/2 mutation negative ovarian cancer cases (P = 0.016). The synonymous TNRC9/TOX3 (Ser51) variant was present at a significantly lower frequency than in patients with familial BRCA1/2 positive breast cancer (P = 0.0002). Our results indicate that variants in CASP8 and TNRC9/TOX3 alter the risk of disease in individuals affected with familial ovarian cancer.

  18. 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

  19. A KRAS-variant in Ovarian Cancer Acts as a Genetic Marker of Cancer Risk

    OpenAIRE

    Ratner, Elena; Lu, Lingeng; Boeke, Marta; Barnett, Rachel; Nallur, Sunitha; Chin, Lena J; Pelletier, Cory; Blitzblau, Rachel; Tassi, Renata; Paranjape, Trupti; Hui, Pei; Andrew K Godwin; Yu, Herbert; Risch, Harvey; Rutherford, Thomas

    2010-01-01

    Ovarian cancer is the single most deadly form of women’s cancer, typically presenting as an advanced disease at diagnosis in part due to a lack of known risk factors or genetic markers of risk. The KRAS oncogene and altered levels of the microRNA let-7 are associated with an increased risk of developing solid tumors. In this study, we investigated a hypothesized association between an increased risk of ovarian cancer and a variant allele of KRAS at rs61764370, referred to as the KRAS-variant,...

  20. Ovarian cancer, the coagulation pathway, and inflammation

    OpenAIRE

    Kavanagh John J; Wang Ena; Wang Xipeng; Freedman Ralph S

    2005-01-01

    Abstract Epithelial ovarian cancer (EOC) represents the most frequent cause of death in the United States from a cancer involving the female genital tract. Contributing to the overall poor outcome in EOC patients, are the metastases to the peritoneum and stroma that are common in this cancer. In one study, cDNA microarray analysis was performed on fresh tissue to profile gene expression in patients with EOC. This study showed a number of genes with significantly altered expression in the pelv...

  1. FDG-PET/CT in advanced ovarian cancer staging: Value and pitfalls in detecting lesions in different abdominal and pelvic quadrants compared with laparoscopy

    International Nuclear Information System (INIS)

    Introduction and aim: Ovarian carcinoma (OC) is a common cancer in the Western Countries, and an important cause of death in patients suffering with gynaecologic malignancies. The majority of patients present with advanced disease at the time of diagnosis. Treatment with debulking surgery followed by chemotherapy is the standard approach while chemotherapy is contemplated when surgery is not possible. A correct pre-operative staging is important to ensure a most appropriate management. Laparoscopy (LPS) is the standard diagnostic tool for the assessment of intraperitoneal infiltration but is invasive and requires general anaesthesia. FDG-PET/CT is increasingly used for staging different types of cancer, and the aim of this study is to assess the value of FDG-PET/CT in staging advanced OC and its sensitivity to detect lesions in different quadrants of the abdominal-pelvic area compared to laparoscopy. Materials and methods: From September 2004 till April 2008, 40 patients with high suspicion of OC were referred to our hospital for diagnostic LPS to explore the possibility of optimal debulking surgery. Those who were not suitable for surgery were referred for chemotherapy. Before chemotherapy, the patients underwent an FDG-PET/CT scan. The findings in 9 quadrants of abdominal-pelvic area (total 360 quadrants) for PET/CT and LPS were recorded and compared. Results: In 14/360 areas (3.8%), surgical evaluation was not possible because of presence of adhesions, thus the number of areas explored by laparoscopy was 346. Tumour was found in 308 quadrants (38 quadrants free of disease). PET/CT was positive in all 40 patients with true negative results in 26/346 quadrants (7.5%), and true positives results in 243/346 quadrants (70.2%). False positive and negative PET/CT results were found in 12/346 and 65/346 quadrants, respectively. False positive PET/CT findings were evenly present in all quadrants. False negative PET/CT findings were present in 31/109 (28.4%) upper

  2. FDG-PET/CT in advanced ovarian cancer staging: Value and pitfalls in detecting lesions in different abdominal and pelvic quadrants compared with laparoscopy

    Energy Technology Data Exchange (ETDEWEB)

    De Iaco, Pierandrea [Department of Gynaecology, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Bologna (Italy); Musto, Alessandra [Department of Nuclear Medicine, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Bologna (Italy); Orazi, Luca [Department of Gynaecology, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Bologna (Italy); Zamagni, Claudio; Rosati, Marta [Department of Medical Oncology, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Bologna (Italy); Allegri, Vincenzo [Department of Nuclear Medicine, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Bologna (Italy); Cacciari, Nicoletta [Department of Medical Oncology, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Bologna (Italy); Al-Nahhas, Adil [Department of Nuclear Medicine, Hammersmith Hospital, London (United Kingdom); Rubello, Domenico, E-mail: domenico.rubello@libero.it [Department of Nuclear Medicine, PET/CT Centre, Radiology, Medical Physics, ' Santa Maria della Misericordia' Hospital, Viale Tre Martiri 140, 45100 Rovigo (Italy); Venturoli, Stefano [Department of Gynaecology, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Bologna (Italy); Fanti, Stefano [Department of Nuclear Medicine, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Bologna (Italy)

    2011-11-15

    Introduction and aim: Ovarian carcinoma (OC) is a common cancer in the Western Countries, and an important cause of death in patients suffering with gynaecologic malignancies. The majority of patients present with advanced disease at the time of diagnosis. Treatment with debulking surgery followed by chemotherapy is the standard approach while chemotherapy is contemplated when surgery is not possible. A correct pre-operative staging is important to ensure a most appropriate management. Laparoscopy (LPS) is the standard diagnostic tool for the assessment of intraperitoneal infiltration but is invasive and requires general anaesthesia. FDG-PET/CT is increasingly used for staging different types of cancer, and the aim of this study is to assess the value of FDG-PET/CT in staging advanced OC and its sensitivity to detect lesions in different quadrants of the abdominal-pelvic area compared to laparoscopy. Materials and methods: From September 2004 till April 2008, 40 patients with high suspicion of OC were referred to our hospital for diagnostic LPS to explore the possibility of optimal debulking surgery. Those who were not suitable for surgery were referred for chemotherapy. Before chemotherapy, the patients underwent an FDG-PET/CT scan. The findings in 9 quadrants of abdominal-pelvic area (total 360 quadrants) for PET/CT and LPS were recorded and compared. Results: In 14/360 areas (3.8%), surgical evaluation was not possible because of presence of adhesions, thus the number of areas explored by laparoscopy was 346. Tumour was found in 308 quadrants (38 quadrants free of disease). PET/CT was positive in all 40 patients with true negative results in 26/346 quadrants (7.5%), and true positives results in 243/346 quadrants (70.2%). False positive and negative PET/CT results were found in 12/346 and 65/346 quadrants, respectively. False positive PET/CT findings were evenly present in all quadrants. False negative PET/CT findings were present in 31/109 (28.4%) upper

  3. Introduction to managing patients with recurrent ovarian cancer.

    Science.gov (United States)

    Gabra, Hani

    2014-12-01

    Ovarian cancer is the 5th most common cancer found in women in the UK. It is the leading cause of death from gynaecological cancer, and is the 4th most common cause of cancer death among UK women. Similar to the majority of other cancers, relative survival rates for ovarian cancer are improving, although 5-year mortality rates remain stubbornly low. The stage of the disease at diagnosis is the single most important determinant of ovarian cancer survival, as many patients first present with advanced disease. Treatment of ovarian cancer involves a combination of 'upfront' primary surgery followed by chemotherapy. Platinum/taxane-based chemotherapy is the recommended standard-of-care first-line chemotherapy, but the majority of patients will relapse with drug-resistant disease within 3-5 years. However, not all patients can continue with platinum combination therapies due to loss of activity or toxicity-related issues, including hypersensitivity, neurotoxicity, alopecia and ototoxicity. Therefore the choice of second-line chemotherapy must take into account factors such as platinum-free treatment interval (PFI); patient's performance status; current symptoms; history of and likely future toxicities while on chemotherapy; dosing schedule requirement; and cost of treatment. A consensus in 2010 established 4 distinct subgroups within the ROC patient population based on the PFI: (platinum sensitive <12 months, partially platinum sensitive 6-12 months, platinum resistant <6 months, and refractory disease ≤4 weeks). Within patients with platinum sensitive disease, those with partially platinum sensitive disease remain the most clinically challenging to manage effectively. Non-platinum based combination therapies, in particular trabectedin with pegylated liposomal doxorubicin (PLD), offers new options together with a significant survival advantage relative to PLD alone for these patients. PMID:26759525

  4. Introduction to managing patients with recurrent ovarian cancer

    Directory of Open Access Journals (Sweden)

    Hani Gabra

    2014-12-01

    Full Text Available Ovarian cancer is the 5th most common cancer found in women in the UK. It is the leading cause of death from gynaecological cancer, and is the 4th most common cause of cancer death among UK women. Similar to the majority of other cancers, relative survival rates for ovarian cancer are improving, although 5-year mortality rates remain stubbornly low. The stage of the disease at diagnosis is the single most important determinant of ovarian cancer survival, as many patients first present with advanced disease. Treatment of ovarian cancer involves a combination of ‘upfront’ primary surgery followed by chemotherapy. Platinum/taxane-based chemotherapy is the recommended standard-of-care first-line chemotherapy, but the majority of patients will relapse with drug-resistant disease within 3-5 years. However, not all patients can continue with platinum combination therapies due to loss of activity or toxicity-related issues, including hypersensitivity, neurotoxicity, alopecia and ototoxicity. Therefore the choice of second-line chemotherapy must take into account factors such as platinum-free treatment interval (PFI; patient's performance status; current symptoms; history of and likely future toxicities while on chemotherapy; dosing schedule requirement; and cost of treatment. A consensus in 2010 established 4 distinct subgroups within the ROC patient population based on the PFI: (platinum sensitive <12 months, partially platinum sensitive 6-12 months, platinum resistant <6 months, and refractory disease ≤4 weeks. Within patients with platinum sensitive disease, those with partially platinum sensitive disease remain the most clinically challenging to manage effectively. Non-platinum based combination therapies, in particular trabectedin with pegylated liposomal doxorubicin (PLD, offers new options together with a significant survival advantage relative to PLD alone for these patients.

  5. Targeted Immune Therapy of Ovarian Cancer

    Science.gov (United States)

    Knutson, Keith L.; Karyampudi, Lavakumar; Lamichhane, Purushottam; Preston, Claudia

    2014-01-01

    Clinical outcomes, such as recurrence free survival and overall survival, in ovarian cancer are quite variable, independent of common characteristics such as stage, response to therapy and grade. This disparity in outcomes warrants further exploration and therapeutic targeting into the interaction between the tumor and host. One compelling host characteristic that contributes both to the initiation and progression of ovarian cancer is the immune system. Hundreds of studies have confirmed a prominent role for the immune system in modifying the clinical course of the disease. Recent studies also show that anti-tumor immunity is often negated by immune regulatory cells present in the tumor microenvironment. Regulatory immune cells also directly enhance the pathogenesis through the release of various cytokines and chemokines, which together form an integrated pathologic network. Thus, in the future, research into immunotherapy targeting ovarian cancer will probably become increasingly focused on combination approaches that simultaneously augment immunity while preventing local immune suppression. In this article, we summarize important immunological targets that influence ovarian cancer outcome as well as include an update on newer immunotherapeutic strategies. PMID:25544369

  6. Nuclear volume and prognosis in ovarian cancer

    DEFF Research Database (Denmark)

    Mogensen, O.; Sørensen, Flemming Brandt; Bichel, P.;

    1992-01-01

    The prognostic value of the volume-weighted mean nuclear volume (MNV) was investigated retrospectively in 100 ovarian cancer patients with FIGO-stage IB-II (n = 51) and stage III-IV (n = 49) serous tumors. No association was demonstrated between the MNV and the survival or between the MNV and two...

  7. Evaluating the ovarian cancer gonadotropin hypothesis

    DEFF Research Database (Denmark)

    Lee, Alice W; Tyrer, Jonathan P; Doherty, Jennifer A;

    2015-01-01

    OBJECTIVE: Ovarian cancer is a hormone-related disease with a strong genetic basis. However, none of its high-penetrance susceptibility genes and GWAS-identified variants to date are known to be involved in hormonal pathways. Given the hypothesized etiologic role of gonadotropins, an assessment o...

  8. 新辅助化疗对晚期卵巢癌的疗效评价%Evaluation on the Efficacy of Neoadjuvant Chemotherapy for Advanced Ovarian Cancer

    Institute of Scientific and Technical Information of China (English)

    孙琮; 童晓文

    2015-01-01

    目的:评价新辅助化疗对晚期卵巢癌的疗效。方法选择2010年3月至2012年10月于同济大学医学院附属第十人民医院就诊的60例晚期卵巢癌患者为研究对象,采用随机数字表法分为结合组和常规组,每组30例。结合组采用术前新辅助化疗再结合手术治疗,常规组进行常规的手术治疗。观察并比较两组患者术后疗效;记录患者术中出血量、手术时间、手术残留情况以及腹膜后淋巴清扫术等各项指标,并进行对比分析。结果结合组总有效率为83.3%,常规组为53.3%,两组疗效比较差异有统计学意义(P<0.05);结合组和常规组患者术中出血量、手术时间比较差异有统计学意义[(426±126) mL比(620±125) mL,(3.4±1.6) h比(4.6±1.4) h](P<0.01),结合组患者术后残留≥2 cm 5例,行腹膜后淋巴清扫术20例,行结肠-直肠切除术1例,常规组患者术后残留≥2 cm 13例,行腹膜后淋巴清扫术9例,行结肠-直肠切除术6例,差异有统计学意义( P<0.05)。结论新辅助化疗对治疗晚期卵巢癌安全、可靠,效果良好。%Objective To evaluate the efficacy of neoadjuvant chemotherapy for advanced ovarian cancer . Methods A total of 60 patients with advanced ovarian cancer admitted in the Tenth People′s Hospital of Tongji Medical College from Mar.2010 to Oct.2012 were selected and randomly divided into the combined treatment group and conventional surgery group,with 30 cases in each group.Patients in both groups were trea-ted with conventional surgery,while patients in the combined treatment group received extra neoadjuvant chem-otherapy.The postoperative efficacy of the two groups was observed,and the amount of intraoperative blood loss,operation time,surgery residues,and retroperitoneal lymph dissection indicators of the two groups were comparatively analyzed.Results The total effective rate of

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

    Directory of Open Access Journals (Sweden)

    Surendra Kumar Saini

    2016-01-01

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

  10. Emerging and Evolving Ovarian Cancer Animal Models

    OpenAIRE

    Bobbs, Alexander S; Jennifer M. Cole; Cowden Dahl, Karen D.

    2015-01-01

    Ovarian cancer (OC) is the leading cause of death from a gynecological malignancy in the United States. By the time a woman is diagnosed with OC, the tumor has usually metastasized. Mouse models that are used to recapitulate different aspects of human OC have been evolving for nearly 40 years. Xenograft studies in immunocompromised and immunocompetent mice have enhanced our knowledge of metastasis and immune cell involvement in cancer. Patient-derived xenografts (PDXs) can accurately reflect ...

  11. The progress of study on pathogenesis in ovarian cancer

    Institute of Scientific and Technical Information of China (English)

    JI Yu-bin; LI Hai-jiao; YU Lei; LIU Guang-da; PANG Lin-lin; YANG Hai-fan

    2008-01-01

    Ovarian cancer is one of the three malignant tumors in female reproductive system, the death rate locates in the first place of gynecological cancer. Most patients are already at the advanced stage when examine their bodies, five-year survival rate are only about 20 % to 30 %. So gynecological cancer has bedome one of tumor which the most waiting to be considered. It happens refer to the incidence of chromosomal abnormalities, cancer gene change. The inactivation of tumor suppressor gene, inhibitor of apoptosis and other genetic changes, the imbalance in the regulatory network due to the interaction of multiple genes and their product. Chromosomal abnormalities play an important role in the development of ovarian cancer, the chromosomes of common characteristic and non-random changes are 1,3, 5, 6, 7, 8, 11, 12, 15, 17, 18, 20, 22 etc. Cancer gene including K-ras, c-erb-B2/HER-2, D1 (CyclinD1), AIB1 etc. K-ras coded protein p21 is activated through point mutation, cause the enzyme activity deprivation of GMP, slowed down the speed of GTP degrdn into GMP, activate target molecule persistently, make cells proliferate persistently, then leading to cancer. HER-2 gene amplification result in the over expression of HER-2 protein, made cells over proliferate,Protein over expression convey the strong signal of proliferation, over activate the early transcription factor and certain gene in the nuclear, then promote the occurrence of cancer. Cyclin D1 promote cells enter from S to Gl phase, thus contribute to the proliferation of cell division, then canceration. AIB1 gene over express, will cause tumor cells immortalized. Tumor suppressor gene, such as BRCA1, p53, p73, p16 etc. The expression depl of BRCA1 protein in ovarian Cystadenocarcinoma prompt that the reduction of BRCA1 protein synthesis, resulting in apoptosis decreased, the cell proliferation disinhibit, then disorder and proliferate, thus leading to cancer, p53 mutation happened in about 30 percents to 80 percents

  12. 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

  13. Effect of paclitaxel liposome combined with nedaplatin on serum HE4, CA125, CA19-9, AFP, CEA and T lymphocyte subsets in patients with advanced ovarian cancer

    Institute of Scientific and Technical Information of China (English)

    Su-Yu Zhu; Jie Tan; Chen-Lu Zhang; Qun-Ying Wu; Xue-Xin Xie; Hua-Fang Yin

    2016-01-01

    Objective:To study the effect of paclitaxel liposome combined with nedaplatin on serum HE4, CA125, CA19-9, AFP, CEA and T lymphocyte subsets in patients with advanced ovarian cancer.Methods:A total of 80 patients with advanced ovarian cancer in our hospital from December 2012 to December 2015 were enrolled in this study. The subjects were divided into control group (n=40) and experiment group (n=40) randomly. The control group were treated with paclitaxel and cisplatin, the experiment group were treated with paclitaxel liposome combined with nedaplatin. 21 days for a period of treatment and the two groups were treated for 3 periods. The serum HE4, CA125, CA19-9, AFP, CEA levels and peripheral blood CD3+, CD4+, CD8+ and NK cells of the two groups before and after treatment were compared. Results:There were no significantly differences of the serum HE4, CA125, CA19-9, AFP, CEA level and peripheral blood CD3+, CD4+, CD8+ and NK cells of the two groups before treatment (P>0.05). The serum HE4, CA125, CA19-9, AFP and CEA level of the two groups after treatment were significantly lower than before treatment (P<0.05), and that of experiment were significantly lower than control group (P<0.05). The peripheral blood CD3+, CD4+, CD8+and NK cells of the two groups after treatment were significantly lower than before treatment (P<0.05), and that of experiment were significantly higher than control group (P<0.05). Conclusions:Paclitaxel liposome combined with nedaplatin can significantly reduce the serum HE4, CA125, CA19-9, AFP and CEA levels, improve peripheral blood CD3+, CD4+, CD8+ and NK levels of patients with advanced ovarian cancer, and it was worthy clinical application.

  14. Intrafamilial disclosure of risk for hereditary breast and ovarian cancer: points to consider

    OpenAIRE

    Black, Lee; McClellan, Kelly A.; Avard, Denise; Knoppers, Bartha Maria

    2012-01-01

    The primary goal of breast and ovarian cancer screening is to minimize the cases of advanced disease and therefore its mortality rate. For hereditary breast and ovarian cancer, one method to reach this goal is to disseminate genetic risk information among family members. However, experience tells us that this information does not always reach family members in a timely manner, if at all. There are many moving parts to a decision to disclose genetic risk information within a family, and the la...

  15. BRCA1 founder mutations compared to ovarian cancer in Belarus.

    Science.gov (United States)

    Savanevich, Alena; Oszurek, Oleg; Lubiński, Jan; Cybulski, Cezary; Dębniak, Tadeusz; Narod, Steven A; Gronwald, Jacek

    2014-09-01

    In Belarus and other Slavic countries, founder mutations in the BRCA1 gene are responsible for a significant proportion of breast cancer cases, but the data on contribution of these mutations to ovarian cancers are limited. To estimate the proportion of ovarian cancers in Belarus, which are dependent on BRCA1 Slavic founder mutations, we sought the presence of three most frequent mutations (BRCA1: 5382insC, C61G and, 4153delA) in 158 consecutive unselected cases of ovarian cancer. One of the three founder mutations was present in 25 of 158 unselected cases of ovarian cancer (15.8 %). We recommend that all cases of ovarian cancer in Belarus be offered genetic testing for these founder mutations. Furthermore, genetic testing of the Belarusian population will provide the opportunity to prevent a significant proportion of ovarian cancer.

  16. How Is Ovarian Cancer Diagnosed?

    Science.gov (United States)

    ... of the procedure, and spending hours in the bathroom. Just before the procedure, the patient is given ... Symptoms of Cancer Treatments & Side Effects Cancer Facts & Statistics News About Cancer Expert Voices Blog Programs & Services ...

  17. 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

  18. 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...

  19. Nanoparticle Albumin-Bound Rapamycin in Treating Patients With Advanced Cancer With mTOR Mutations

    Science.gov (United States)

    2016-04-18

    Advanced Malignant Neoplasm; Cervical Squamous Cell Carcinoma; Endometrial Carcinoma; Malignant Uterine Neoplasm; Recurrent Bladder Carcinoma; Recurrent Breast Carcinoma; Recurrent Cervical Carcinoma; Recurrent Head and Neck Carcinoma; Recurrent Malignant Neoplasm; Recurrent Ovarian Carcinoma; Recurrent Prostate Carcinoma; Recurrent Renal Cell Carcinoma; Solid Neoplasm; Stage III Bladder Cancer; Stage III Prostate Cancer; Stage III Renal Cell Cancer; Stage IIIA Breast Cancer; Stage IIIA Cervical Cancer; Stage IIIA Ovarian Cancer; Stage IIIB Breast Cancer; Stage IIIB Cervical Cancer; Stage IIIB Ovarian Cancer; Stage IIIC Breast Cancer; Stage IIIC Ovarian Cancer; Stage IV Breast Cancer; Stage IV Ovarian Cancer; Stage IV Prostate Cancer; Stage IV Renal Cell Cancer; Stage IVA Bladder Cancer; Stage IVA Cervical Cancer; Stage IVB Bladder Cancer; Stage IVB Cervical Cancer

  20. 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...

  1. 甘氨双唑钠(CMNa)联合紫杉醇卡铂化疗对中晚期卵巢癌术后CA125升高的影响%Effects of CMNa combined with paclitaxel and carboplatin on elevated CA125 levels in post-operation advanced ovarian cancer patients

    Institute of Scientific and Technical Information of China (English)

    Kaijian Lei; Yuming Jia; Jing Wang; Yiping Du

    2008-01-01

    Objective: To investigate the effects of CMNa combined with paclitaxel and carboplatin on elevated CA125 levels in post-operation advanced ovarian cancer patients. Methods: The effects of CMNa combined with paclitaxel and carboplatin on elevated CA125 levels in 25 post-operation advanced ovarian cancer patients were retrospectively analyzed and compared with those in 20 control cases. Results: After 1 cycle of chemotherapy, CA125 levels had decreasing trend compared with control, but had no statistical significance. While after two cycles of chemotherapy, CA125 levels decreased more rapidly compared with those in control. Side effects in two groups were alike. Conclusion: CMNa combined with paclitaxel and carboplatine has a stronger effect on the decrease of elevated CA125 levels than paclitaxel and carboplatin have in the treatment of post-operation advanced ovarian cancer, which indicates that CMNa has chemo-sensitizing effects on chemotherapy of paclitaxel and carboplatin.

  2. Risk of prostate, ovarian, and endometrial cancer among relatives of women with breast cancer.

    OpenAIRE

    Tulinius, H.; Egilsson, V.; Olafsdóttir, G. H.; Sigvaldason, H

    1992-01-01

    OBJECTIVE--To investigate the risk of prostate, ovarian, and endometrial cancer among relatives of patients with breast cancer. DESIGN--Cohort study of 947 pedigrees in which the proband had breast cancer, linked with the Icelandic cancer registry. SETTING--Iceland. SUBJECTS--The 947 pedigrees included 29,725 people, of whom 1539 had breast cancer, 467 had prostate cancer, 135 ovarian cancer, and 105 endometrial cancer. MAIN OUTCOME MEASURES--Risk of prostate, ovarian, and endometrial cancer ...

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  4. Mathematical models of breast and ovarian cancers.

    Science.gov (United States)

    Botesteanu, Dana-Adriana; Lipkowitz, Stanley; Lee, Jung-Min; Levy, Doron

    2016-07-01

    Women constitute the majority of the aging United States (US) population, and this has substantial implications on cancer population patterns and management practices. Breast cancer is the most common women's malignancy, while ovarian cancer is the most fatal gynecological malignancy in the US. In this review, we focus on these subsets of women's cancers, seen more commonly in postmenopausal and elderly women. In order to systematically investigate the complexity of cancer progression and response to treatment in breast and ovarian malignancies, we assert that integrated mathematical modeling frameworks viewed from a systems biology perspective are needed. Such integrated frameworks could offer innovative contributions to the clinical women's cancers community, as answers to clinical questions cannot always be reached with contemporary clinical and experimental tools. Here, we recapitulate clinically known data regarding the progression and treatment of the breast and ovarian cancers. We compare and contrast the two malignancies whenever possible in order to emphasize areas where substantial contributions could be made by clinically inspired and validated mathematical modeling. We show how current paradigms in the mathematical oncology community focusing on the two malignancies do not make comprehensive use of, nor substantially reflect existing clinical data, and we highlight the modeling areas in most critical need of clinical data integration. We emphasize that the primary goal of any mathematical study of women's cancers should be to address clinically relevant questions. WIREs Syst Biol Med 2016, 8:337-362. doi: 10.1002/wsbm.1343 For further resources related to this article, please visit the WIREs website. PMID:27259061

  5. Identification of candidate epigenetic biomarkers for ovarian cancer detection

    NARCIS (Netherlands)

    Huang, Yi-Wen; Jansen, Rachel A.; Fabbri, Enrica; Potter, Dustin; Liyanarachchi, Sandya; Chan, Michael W. Y.; Liu, Joseph C.; Crijns, Anne P. G.; Brown, Robert; Nephew, Kenneth P.; Van Der Zee, Ate G. J.; Cohn, David E.; Yan, Pearlly S.; Huang, Tim H. -M.; Lin, Huey-Jen L.

    2009-01-01

    Ovarian cancer ranks the most lethal among gynecologic neoplasms in women. To develop potential biomarkers for diagnosis, we have identified five novel genes (CYP39A1, GTF2A1, FOXD4L4, EBP, and HAAO) that are hypermethylated in ovarian tumors, compared with the non-malignant normal ovarian surface e

  6. 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 ...

  7. 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...

  8. Genetics Home Reference: ovarian cancer

    Science.gov (United States)

    ... that form the lining of the abdomen (the peritoneum). This form of cancer, called primary peritoneal cancer, ... that begin in the ovaries, fallopian tubes, and peritoneum are so similar and spread easily from one ...

  9. Three-photon imaging of ovarian cancer

    Science.gov (United States)

    Barton, Jennifer K.; Amirsolaimani, Babak; Rice, Photini; Hatch, Kenneth; Kieu, Khanh

    2016-02-01

    Optical imaging methods have the potential to detect ovarian cancer at an early, curable stage. Optical imaging has the disadvantage that high resolution techniques require access to the tissue of interest, but miniature endoscopes that traverse the natural orifice of the reproductive tract, or access the ovaries and fallopian tubes through a small incision in the vagina wall, can provide a minimally-invasive solution. We have imaged both rodent and human ovaries and fallopian tubes with a variety of endoscope-compatible modalities. The recent development of fiber-coupled femtosecond lasers will enable endoscopic multiphoton microscopy (MPM). We demonstrated two- and three-photon excited fluorescence (2PEF, 3PEF), and second- and third-harmonic generation microscopy (SHG, THG) in human ovarian and fallopian tube tissue. A study was undertaken to understand the mechanisms of contrast in these images. Six patients (normal, cystadenoma, and ovarian adenocarcinoma) provided ovarian and fallopian tube biopsies. The tissue was imaged with three-dimensional optical coherence tomography, multiphoton microscopy, and frozen for histological sectioning. Tissue sections were stained with hematoxylin and eosin, Masson's trichrome, and Sudan black. Approximately 1 μm resolution images were obtained with an excitation source at 1550 nm. 2PEF signal was absent. SHG signal was mainly from collagen. 3PEF and THG signal came from a variety of sources, including a strong signal from fatty connective tissue and red blood cells. Adenocarcinoma was characterized by loss of SHG signal, whereas cystic abnormalities showed strong SHG. There was limited overlap of two- and three- photon signals, suggesting that three-photon imaging can provide additional information for early diagnosis of ovarian cancer.

  10. Agreement for depression diagnosis between DSM-IV-TR criteria, three validated scales, oncologist assessment, and psychiatric clinical interview in elderly patients with advanced ovarian cancer

    Directory of Open Access Journals (Sweden)

    Rhondali W

    2015-07-01

    Full Text Available Wadih Rhondali,1 Gilles Freyer,2 Virginie Adam,3 Marilène Filbet,4 Martine Derzelle,5 Gaelle Abgrall-Barbry,6 Sophie Bourcelot,7 Jean-Louis Machavoine,8 Muriel Chomat-Neyraud,9 Olivier Gisserot,10 Rémi Largillier,11 Annick Le Rol,12 Frank Priou,13 Pierre Saltel,14 Claire Falandry15 1Clinique Mon Repos, Clinea, Marseille, France; 2Medical Oncology Unit, Centre Hospitalier Lyon Sud, Université Lyon 1, Pierre-Benite, France; 3Institut de Cancérologie de Lorraine Alexis Vautrin, Vandoeuvre-lès-Nancy, France; 4Palliative Unit, Centre Hospitalier Lyon Sud, Université Lyon 1, Pierre-Benite, France; 5Institut Jean Godinot, Reims, France; 6Tenon Hospital, Assistance Publique Hôpitaux de Paris, Paris, France; 7Centre Léon Bérard, Lyon, France; 8Centre François Baclesse, Caen, France; 9Centre Hospitalier de la région d’Annecy, Pringy, France; 10Hôpital d’Instruction des Armées Sainte-Anne, Toulon, France; 11Centre Azuréen de Cancérologie, Mougins, France; 12Medical Oncology, Hôpital Perpétuel Secours, Levallois-Perret, France; 13Medical Oncology, Centre Hospitalier Départemental Les Oudairies, La Roche-sur-Yon, France; 14Supportive Care Department, Centre Léon Bérard, Lyon, France; 15Geriatrics and Oncology Unit, Centre Hospitalier Lyon Sud, Université Lyon 1, Pierre-Bénite, France Background: Depression, a major outcome in cancer patients, is often evaluated by physicians relying on their clinical impressions rather than patient self-report. Our aim was to assess agreement between patient self-reported depression, oncologist assessment (OA, and psychiatric clinical interview (PCI in elderly patients with advanced ovarian cancer (AOC.Methods: This analysis was a secondary endpoint of the Elderly Women AOC Trial 3 (EWOT3, designed to assess the impact of geriatric covariates, notably depression, on survival in patients older than 70 years of age. Depression was assessed using the Geriatric Depression Scale-30 (GDS, the Hospital

  11. 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.

  12. 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

  13. Exosomal transfer of stroma-derived miR21 confers paclitaxel resistance in ovarian cancer cells through targeting APAF1

    OpenAIRE

    Au Yeung, Chi Lam; Co, Ngai-Na; Tsuruga, Tetsushi; Yeung, Tsz-Lun; Kwan, Suet-Ying; Leung, Cecilia S.; LI, YONG; Lu, Edward S.; Kwan, Kenny; Wong, Kwong-Kwok; Schmandt, Rosemarie; Lu, Karen H.; Mok, Samuel C.

    2016-01-01

    Advanced ovarian cancer usually spreads to the visceral adipose tissue of the omentum. However, the omental stromal cell-derived molecular determinants that modulate ovarian cancer growth have not been characterized. Here, using next-generation sequencing technology, we identify significantly higher levels of microRNA-21 (miR21) isomiRNAs in exosomes and tissue lysates isolated from cancer-associated adipocytes (CAAs) and fibroblasts (CAFs) than in those from ovarian cancer cells. Functional ...

  14. 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...

  15. Tumor microenvironment: The culprit for ovarian cancer metastasis?

    Science.gov (United States)

    Luo, Zhongyue; Wang, Qiu; Lau, Wayne Bond; Lau, Bonnie; Xu, Lian; Zhao, Linjie; Yang, Huiliang; Feng, Min; Xuan, Yu; Yang, Yanfei; Lei, Lingzi; Wang, Chenlu; Yi, Tao; Zhao, Xia; Wei, Yuquan; Zhou, Shengtao

    2016-07-28

    Despite chemotherapy and surgical debulking options, ovarian cancer recurs and disseminates frequently, with poor prognosis. However, the molecular mechanisms underlying ovarian cancer metastasis still remain unelucidated. The tumor microenvironment, consisting of stromal cells (including fibroblasts, macrophages, regulatory T cells, myeloid-derived suppressor cells, endothelial cells, pericytes and platelets), the extracellular matrix component (EMC) (including inflammatory cytokines, chemokines, matrix metalloproteinases, integrins, and other secreted molecules) and exosomes (small extracellular vesicles loaded with molecules), establishes an autocrine-paracrine communication circuit that reinforces invasion and cancer cell metastasis via reciprocal signaling. Recent evidences have unraveled the significant contribution of tumor microenvironment to ovarian cancer metastasis. In this review, we provide a comprehensive landscape of the reciprocity between tumor stroma and ovarian cancer cells upon metastasis, aiming to offer novel clues on the development of novel diagnostic biomarkers and therapeutic targets for ovarian cancer in future clinical practice. PMID:27131957

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Risk of Ovarian Cancer Relapse Score

    Science.gov (United States)

    Rizzuto, Ivana; Stavraka, Chara; Chatterjee, Jayanta; Borley, Jane; Hopkins, Thomas Glass; Gabra, Hani; Ghaem-Maghami, Sadaf; Huson, Les; Blagden, Sarah P.

    2015-01-01

    Objective The aim of this study was to construct a prognostic index that predicts risk of relapse in women who have completed first-line treatment for ovarian cancer (OC). Methods A database of OC cases from 2000 to 2010 was interrogated for International Federation of Gynecology and Obstetrics stage, grade and histological subtype of cancer, preoperative and posttreatment CA-125 level, presence or absence of residual disease after cytoreductive surgery and on postchemotherapy computed tomography scan, and time to progression and death. The strongest predictors of relapse were included into an algorithm, the Risk of Ovarian Cancer Relapse (ROVAR) score. Results Three hundred fifty-four cases of OC were analyzed to generate the ROVAR score. Factors selected were preoperative serum CA-125, International Federation of Gynecology and Obstetrics stage and grade of cancer, and presence of residual disease at posttreatment computed tomography scan. In the validation data set, the ROVAR score had a sensitivity and specificity of 94% and 61%, respectively. The concordance index for the validation data set was 0.91 (95% confidence interval, 0.85-0.96). The score allows patient stratification into low (0.67) probability of relapse. Conclusions The ROVAR score stratifies patients according to their risk of relapse following first-line treatment for OC. This can broadly facilitate the appropriate tailoring of posttreatment care and support. PMID:25647256

  18. Dietary influences on survival after ovarian cancer.

    Science.gov (United States)

    Nagle, Christina M; Purdie, David M; Webb, Penelope M; Green, Adèle; Harvey, Philip W; Bain, Christopher J

    2003-08-20

    We evaluated the effects of various food groups and micronutrients in the diet on survival among women who originally participated in a population-based case-control study of ovarian cancer conducted across 3 Australian states between 1990 and 1993. This analysis included 609 women with invasive epithelial ovarian cancer, primarily because there was negligible mortality in women with borderline tumors. The women's usual diet was assessed using a validated food frequency questionnaire. Deaths in the cohort were identified using state-based cancer registries and the Australian National Death Index (NDI). Crude 5-year survival probabilities were estimated using the Kaplan-Meier technique, and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were obtained from Cox regression models. After adjusting for important confounding factors, a survival advantage was observed for those who reported higher intake of vegetables in general (HR = 0.75, 95% CI = 0.57-0.99, p-value trend 0.01 for the highest third, compared to the lowest third), and cruciferous vegetables in particular (HR = 0.75, 95% CI = 0.57-0.98, p-value trend 0.03), and among women in the upper third of intake of vitamin E (HR = 0.76, 95% CI = 0.58-1.01, p-value trend 0.04). Inverse associations were also seen with protein (p-value trend 0.09), red meat (p-value trend 0.06) and white meat (p-value trend 0.07), and modest positive trends (maximum 30% excess) with lactose (p-value trend 0.04), calcium and dairy products. Although much remains to be learned about the influence of nutritional factors after a diagnosis of ovarian cancer, our study suggests the possibility that a diet high in vegetable intake may help improve survival. PMID:12800204

  19. A phase 3 trial of bevacizumab in ovarian cancer

    DEFF Research Database (Denmark)

    Perren, Timothy J; Swart, Ann Marie; Pfisterer, Jacobus;

    2011-01-01

    Angiogenesis plays a role in the biology of ovarian cancer. We examined the effect of bevacizumab, the vascular endothelial growth factor inhibitor, on survival in women with this disease.......Angiogenesis plays a role in the biology of ovarian cancer. We examined the effect of bevacizumab, the vascular endothelial growth factor inhibitor, on survival in women with this disease....

  20. Tubal ligation and risk of ovarian cancer subtypes

    DEFF Research Database (Denmark)

    Sieh, Weiva; Salvador, Shannon; McGuire, Valerie;

    2013-01-01

    Tubal ligation is a protective factor for ovarian cancer, but it is unknown whether this protection extends to all invasive histological subtypes or borderline tumors. We undertook an international collaborative study to examine the association between tubal ligation and ovarian cancer subtypes....

  1. Acute onset of ovarian dysfunction in young females after start of cancer treatment

    DEFF Research Database (Denmark)

    Mörse, Helena; Elfving, Maria; Lindgren, Anna;

    2013-01-01

    Female childhood cancer survivors are at risk of ovarian failure and premature ovarian insufficiency. We hereby present an interim analysis of a prospective observational study of ovarian function during cancer treatment of young females in relation to clinical factors.......Female childhood cancer survivors are at risk of ovarian failure and premature ovarian insufficiency. We hereby present an interim analysis of a prospective observational study of ovarian function during cancer treatment of young females in relation to clinical factors....

  2. Association of vitamin D levels and risk of ovarian cancer

    DEFF Research Database (Denmark)

    Ong, Jue-Sheng; Cuellar-Partida, Gabriel; Lu, Yi;

    2016-01-01

    BACKGROUND: In vitro and observational epidemiological studies suggest that vitamin D may play a role in cancer prevention. However, the relationship between vitamin D and ovarian cancer is uncertain, with observational studies generating conflicting findings. A potential limitation of observatio...

  3. 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...

  4. Symptom interpretation and health care seeking in ovarian cancer

    DEFF Research Database (Denmark)

    Seibaek, Lene; Petersen, Lone K; Blaakær, Jan;

    2011-01-01

    BACKGROUND: Ovarian cancer is the leading cause of death among women suffering from gynaecological malignancies in the Western world. Worldwide, approximately 200,000 women are diagnosed with the disease each year. This article deals with the health care seeking and symptom interpretation process...... with ovarian cancer. These results were combined with findings from semi-structured qualitative research interviews on women's bodily experiences with symptom development. RESULTS: A number of 663 Danish women with ovarian cancer attended 27 different kinds of primary health care providers in a total of 14...... knowledge concerning the onset of their symptoms. The early symptoms of ovarian cancer might be uncharacteristic and non-disease-specific when interpreted as personal experiences, but they had similarities when analysed together. CONCLUSIONS: Diagnostic delay in ovarian cancer seems far from being...

  5. 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...

  6. 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...

  7. Proteomics Analysis for Finding Serum Markers of Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Yushan Cheng

    2014-01-01

    Full Text Available A combination of peptide ligand library beads (PLLB and 1D gel liquid chromatography-mass spectrometry/mass spectrometry (1DGel-LC-MS/MS was employed to analyze serum samples from patients with ovarian cancer and from healthy controls. Proteomic analysis identified 1200 serum proteins, among which 57 proteins were upregulated and 10 were downregulated in the sera from cancer patients. Retinol binding protein 4 (RBP4 is highly upregulated in the ovarian cancer serum samples. ELISA was employed to measure plasma concentrations of RBP4 in 80 samples from ovarian cancer patients, healthy individuals, myoma patients, and patients with benign ovarian tumor, respectively. The plasma concentrations of RBP4 ranging from 76.91 to 120.08 ng/mL with the mean value 89.13±1.67 ng/mL in ovarian cancer patients are significantly higher than those in healthy individuals (10.85±2.38 ng/mL. Results were further confirmed with immunohistochemistry, demonstrating that RBP4 expression levels in normal ovarian tissue were lower than those in ovarian cancer tissues. Our results suggested that RBP4 is a potential biomarker for diagnostic of screening ovarian cancer.

  8. Dihydroartemisinin is an inhibitor of ovarian cancer cell growth

    Institute of Scientific and Technical Information of China (English)

    Yang JIAO; Chun-min GE; Qing-hui MENG; Jian-ping CAO; Jian TONG; Sai-jun FAN

    2007-01-01

    Aim: To investigate the anticancer activity of dihydroartemisinin (DHA), a deriva-tive of antimalaria drug artemisinin in a panel of human ovarian cancer cell lines. Methods: Cell growth was determined by the MTT viability assay. Apoptosis and cell cycle progression were evaluated by a DNA fragmentation gel electro-phoresis, flow cytometry assay, and TUNEL assay; protein and mRNA expression were analyzed by Western blotting and RT-PCR assay. Results: Artemisinin and its derivatives, including artesunate, arteether, artemether, arteannuin, and DHA, exhibit anticancer growth activities in human ovarian cancer cells. Among them, DHA is the most effective in inhibiting cell growth. Ovarian cancer cell lines are more sensitive (5-10-fold) to DHA treatment compared to normal ovarian cell lines. DHA at micromolar dose levels exhibits a dose- and time-dependent cyto-toxicity in ovarian cancer cell lines. Furthermore, DHA induced apoptosis and G2 cell cycle arrest, accompanied by a decrease of Bcl-xL and Bcl-2 and an increase of Bax and Bad. Conclusion: The promising results show for the first time that DHA inhibits the growth of human ovarian cancer cells. The selective inhibition of ovarian cancer cell growth, apoptosis induction, and G2 arrest provide in vitro evidence for further studies of DHA as a possible anticancer drug in the clinical treatment of ovarian cancer.

  9. Ovarian cancer susceptibility alleles and risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers

    NARCIS (Netherlands)

    Ramus, S.J.; Antoniou, A.C.; Kuchenbaecker, K.B.; Soucy, P.; Beesley, J.; Chen, X.; McGuffog, L.; Sinilnikova, O.M.; Healey, S.; Barrowdale, D.; Lee, A.; Thomassen, M.; Gerdes, A.M.; Kruse, T.A.; Jensen, U.B.; Skytte, A.B.; Caligo, M.A.; Liljegren, A.; Lindblom, A.; Olsson, H.; Kristoffersson, U.; Stenmark-Askmalm, M.; Melin, B.; Swe, B.; Domchek, S.M.; Nathanson, K.L.; Rebbeck, T.R.; Jakubowska, A.; Lubinski, J.; Jaworska, K.; Durda, K.; Zlowocka, E.; Gronwald, J.; Huzarski, T.; Byrski, T.; Cybulski, C.; Toloczko-Grabarek, A.; Osorio, A.; Benitez, J.; Duran, M.; Tejada, M.I.; Hamann, U.; Rookus, M.; Leeuwen, F.E. van; Aalfs, C.M.; Meijers-Heijboer, H.E.; Asperen, C.J. van; Roozendaal, K.E. van; Hoogerbrugge-van der Linden, N.; Collee, J.M.; Kriege, M.; Luijt, R.B. van der; Hebon, .; Embrace, .; Peock, S.; Frost, D.; Ellis, S.D.; Platte, R.; Fineberg, E.; Evans, D.G.; Lalloo, F.; Jacobs, C.; Eeles, R.; Adlard, J.; Davidson, R.; Eccles, D.; Cole, T.; Cook, J.; Paterson, J.; Douglas, F.; Brewer, C.; Hodgson, S.; Morrison, P.J.; Walker, L.; Porteous, M.E.; Kennedy, M.J.; Pathak, H.; Godwin, A.K.; Stoppa-Lyonnet, D.; Caux-Moncoutier, V.; Pauw, A. de; Gauthier-Villars, M.; Mazoyer, S.; Leone, M.; Calender, A.; Lasset, C.; Bonadona, V.; Hardouin, A.; Berthet, P.; Bignon, Y.J.; Uhrhammer, N.; Faivre, L.; Loustalot, C.; Gemo, .; Buys, S.; Daly, M.; Miron, A.; Terry, M.B.; Chung, W.K.; John, E.M.; Ligtenberg, M.J.

    2012-01-01

    Germline mutations in BRCA1 and BRCA2 are associated with increased risks of breast and ovarian cancer. A genome-wide association study (GWAS) identified six alleles associated with risk of ovarian cancer for women in the general population. We evaluated four of these loci as potential modifiers of

  10. Ovarian cancer susceptibility alleles and risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers

    DEFF Research Database (Denmark)

    Ramus, Susan J; Antoniou, Antonis C; Kuchenbaecker, Karoline B;

    2012-01-01

    Germline mutations in BRCA1 and BRCA2 are associated with increased risks of breast and ovarian cancer. A genome-wide association study (GWAS) identified six alleles associated with risk of ovarian cancer for women in the general population. We evaluated four of these loci as potential modifiers ...

  11. 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

  12. Integrated proteogenomic characterization of human high grade serous ovarian cancer

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Hui; Liu, Tao; Zhang, Zhen; Payne, Samuel H.; Zhang, Bai; McDermott, Jason E.; Zhou, Jian-Ying; Petyuk, Vladislav A.; Chen, Li; Ray, Debjit; Sun, Shisheng; Yang, Feng; Chen, Lijun; Wang, Jing; Shah, Punut; Cha, Seong Won; Aiyetan, Paul; Woo, Sunghee; Tian, Yuan; Gritsenko, Marina A.; Clauss, Therese RW; Choi, Caitlin; Monroe, Matthew E.; Thomas, Stefani N.; Nie, Song; Wu, Chaochao; Moore, Ronald J.; Yu, Kun-Hsing; Tabb, David L.; Fenyo, David; Bafna, Vineet; Wang, Yue; Rodriguez, Henry; Boja, Emily; Hiltket, Tara; Rivers, Robert; Sokoll, Lori J.; Zhu, Heng; Shih, Ie-Ming; Cope, Leslie; Pandey, Akhilesh; Zhang, Bing; Snyder, Michael; Levine, Douglas; Smith, Richard D.; Chan, Daniel W.; Rodland, Karin D.

    2016-07-28

    Ovarian cancer remains the most lethal gynecological malignancy in the developed world, despite recent advances in genomic information and treatment. To better understand this disease, define an integrated proteogenomic landscape, and identify factors associated with homologous repair deficiency (HRD) and overall survival, we performed a comprehensive proteomic characterization of ovarian high-grade serous carcinomas (HGSC) previously characterized by The Cancer Genome Atlas (TCGA). We observed that messenger RNA transcript abundance did not reliably predict abundance for 10,030 proteins across 174 tumors. Clustering of tumors based on protein abundance identified five subtypes, two of which correlated robustly with mesenchymal and proliferative subtypes, while tumors characterized as immunoreactive or differentiated at the transcript level were intermixed at the protein level. At the genome level, HGSC is characterized by a complex landscape of somatic copy number alterations (CNA), which individually do not correlate significantly with survival. Correlation of CNAs with protein abundances identified loci with significant trans regulatory effects mapping to pathways associated with proliferation, cell motility/invasion, and immune regulation, three known hallmarks of cancer. Using the trans regulated proteins we also created models significantly correlated with patient survival by multivariate analysis. Integrating protein abundance with specific post-translational modification data identified subnetworks correlated with HRD status; specifically, acetylation of Lys12 and Lys16 on histone H4 was associated with HRD status. Using quantitative phosphoproteomics data covering 4,420 proteins as reflective of pathway activity, we identified the PDGFR and VEGFR signaling pathways as significantly up-regulated in patients with short overall survival, independent of PDGFR and VEGFR protein levels, potentially informing the use of anti-angiogenic therapies. Components of

  13. Ovarian Cancer: A Clinical Challenge That Needs Some Basic Answers

    OpenAIRE

    CRIJNS, ANNE P.G.; Fehrmann, Rudolf S. N.; Steven de Jong; Frans Gerbens; Gert Jan Meersma; Klip, Harry G.; Harry Hollema; Hofstra, Robert M. W.; te Meerman, Gerard J.; de Vries, Elisabeth G.E.; Ate G J van der Zee

    2009-01-01

    Editors' Summary Background. Ovarian cancer kills more than 100,000 women every year and is one of the most frequent causes of cancer death in women in Western countries. Most ovarian cancers develop when an epithelial cell in one of the ovaries (two small organs in the pelvis that produce eggs) acquires genetic changes that allow it to grow uncontrollably and to spread around the body (metastasize). In its early stages, ovarian cancer is confined to the ovaries and can often be treated succe...

  14. 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

  15. 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.

  16. 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

  17. 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...

  18. Quantitative analysis of cell-free DNA in ovarian cancer

    OpenAIRE

    Shao, Xuefeng; He, Yan; Ji, Min; Chen, Xiaofang; Qi, Jing; SHI, Wei; HAO, TIANBO; JU, SHAOQING

    2015-01-01

    The aim of the present study was to investigate the association between cell-free DNA (cf-DNA) levels and clinicopathological characteristics of patients with ovarian cancer using a branched DNA (bDNA) technique, and to determine the value of quantitative cf-DNA detection in assisting with the diagnosis of ovarian cancer. Serum specimens were collected from 36 patients with ovarian cancer on days 1, 3 and 7 following surgery, and additional serum samples were also collected from 22 benign ova...

  19. Methylseleninic acid sensitizes Notch3-activated OVCA429 ovarian cancer cells to carboplatin.

    Directory of Open Access Journals (Sweden)

    Tiffany J Tzeng

    Full Text Available Ovarian cancer, the deadliest of gynecologic cancers, is usually not diagnosed until advanced stages. Although carboplatin has been popular for treating ovarian cancer for decades, patients eventually develop resistance to this platinum-containing drug. Expression of neurogenic locus notch homolog 3 (Notch3 is associated with chemoresistance and poor overall survival in ovarian cancer patients. Overexpression of NICD3 (the constitutively active form of Notch3 in OVCA429 ovarian cancer cells (OVCA429/NICD3 renders them resistance to carboplatin treatment compared to OVCA429/pCEG cells expressing an empty vector. We have previously shown that methylseleninic acid (MSeA induces oxidative stress and activates ataxia-telangiectasia mutated and DNA-dependent protein kinase in cancer cells. Here we tested the hypothesis that MSeA and carboplatin exerted a synthetic lethal effect on OVCA429/NICD3 cells. Co-treatment with MSeA synergistically sensitized OVCA429/NICD3 but not OVCA429/pCEG cells to the killing by carboplatin. This synergism was associated with a cell cycle exit at the G2/M phase and the induction of NICD3 target gene HES1. Treatment of N-acetyl cysteine or inhibitors of the above two kinases did not directly impact on the synergism in OVCA429/NICD3 cells. Taken together, these results suggest that the efficacy of carboplatin in the treatment of high grade ovarian carcinoma can be enhanced by a combinational therapy with MSeA.

  20. Tissue Biomarkers in Prognostication of Serous Ovarian Cancer following Neoadjuvant Chemotherapy

    OpenAIRE

    Binny Khandakar; Sandeep R Mathur; Lalit Kumar; Sunesh Kumar; Siddhartha Datta Gupta; Venkateswaran K Iyer; Kalaivani, M.

    2014-01-01

    Serous ovarian cancer (SOC) is a significant cause of morbidity and mortality in females with poor prognosis because of advanced stage at presentation. Recently, neoadjuvant chemotherapy (NACT) is being used for management of advanced SOC, but role of tissue biomarkers in prognostication following NACT is not well established. The study was conducted on advanced stage SOC patients (n = 100) that were treated either conventionally (n = 50) or with NACT (n = 50), followed by surgery. In order t...

  1. 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

  2. Quantitative analysis of cell-free DNA in ovarian cancer

    Science.gov (United States)

    SHAO, XUEFENG; He, YAN; JI, MIN; CHEN, XIAOFANG; QI, JING; SHI, WEI; HAO, TIANBO; JU, SHAOQING

    2015-01-01

    The aim of the present study was to investigate the association between cell-free DNA (cf-DNA) levels and clinicopathological characteristics of patients with ovarian cancer using a branched DNA (bDNA) technique, and to determine the value of quantitative cf-DNA detection in assisting with the diagnosis of ovarian cancer. Serum specimens were collected from 36 patients with ovarian cancer on days 1, 3 and 7 following surgery, and additional serum samples were also collected from 22 benign ovarian tumor cases, and 19 healthy, non-cancerous ovaries. bDNA techniques were used to detect serum cf-DNA concentrations. All data were analyzed using SPSS version 18.0. The cf-DNA levels were significantly increased in the ovarian cancer group compared with those of the benign ovarian tumor group and healthy ovarian group (P<0.01). Furthermore, cf-DNA levels were significantly increased in stage III and IV ovarian cancer compared with those of stages I and II (P<0.01). In addition, cf-DNA levels were significantly increased on the first day post-surgery (P<0.01), and subsequently demonstrated a gradual decrease. In the ovarian cancer group, the area under the receiver operating characteristic curve of cf-DNA and the sensitivity were 0.917 and 88.9%, respectively, which was higher than those of cancer antigen 125 (0.724, 75%) and human epididymis protein 4 (0.743, 80.6%). There was a correlation between the levels of serum cf-DNA and the occurrence and development of ovarian cancer in the patients evaluated. bDNA techniques possessed higher sensitivity and specificity than other methods for the detection of serum cf-DNA in patients exhibiting ovarian cancer, and bDNA techniques are more useful for detecting cf-DNA than other factors. Thus, the present study demonstrated the potential value for the use of bDNA as an adjuvant diagnostic method for ovarian cancer. PMID:26788153

  3. 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.

  4. Therapeutic efficacy of an oncolytic adenovirus containing RGD ligand in minor capsid protein IX and Fiber, Δ24DoubleRGD, in an ovarian cancer model

    Directory of Open Access Journals (Sweden)

    Anton V Borovjagin

    2012-02-01

    Full Text Available Ovarian cancer is the leading cause of gynecological disease death despite advances in medicine. Therefore, novel strategies are required for ovarian cancer therapy. Conditionally replicative adenoviruses (CRAds, genetically modified as anti-cancer therapeutics, are one of the most attractive candidate agents for cancer therapy. However, a paucity of coxsackie B virus and adenovirus receptor (CAR expression on the surface of ovarian cancer cells has impeded treatment of ovarian cancer using this approach.This study sought to engineer a CRAd with enhanced oncolytic ability in ovarian cancer cells, “Δ24DoubleRGD.” Δ24DoubleRGD carries an arginine-glycine-aspartate (RGD motif incorporated into both fiber and capsid protein IX (pIX and its oncolytic efficacy was evaluated in ovarian cancer. In vitro analysis of cell viability showed that infection of ovarian cancer cells with Δ24DoubleRGD leads to increased cell killing relative to the control CRAds. Data from this study suggested that not only an increase in number of RGD motifs on the CRAd capsid, but also a change in the repertoir of targeted integrins could lead to enhanced oncolytic potency of Δ24DoubleRGD in ovarian cancer cells in vitro. In an intraperitoneal model of ovarian cancer, mice injected with Δ24DoubleRGD showed, however, a similar survival rate as mice treated with control CRAds.

  5. 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

  6. Ovarian Cancer and BRCA1/2 Testing: Opportunities to improve clinical care and disease prevention

    Directory of Open Access Journals (Sweden)

    Katherine eKarakasis

    2016-05-01

    Full Text Available Without prevention or screening options available, ovarian cancer is the most lethal malignancy of the female reproductive tract. High grade serous ovarian cancer (HGSOC is the most common histologic subtype, and the role of germline BRCA1/2 mutation in predisposition and prognosis is established. Given the targeted treatment opportunities with PARP inhibitors, a predictive role for BRCA1/2 mutation has emerged. Despite recommendations to provide BRCA1/2 testing to all women with histologically confirmed HGSOC, uniform implementation remains challenging. The opportunity to review and revise genetic screening and testing practices will identify opportunities where universal adoption of BRCA1/2 mutation testing will impact and improve treatment of women with ovarian cancer. Improving education and awareness of genetic testing for women with cancer, as well as the broader general community, will help focus much needed attention on opportunities to advance prevention and screening programs in ovarian cancer. This is imperative not only for women with cancer, those at risk of developing cancer, but also for their first-degree relatives. In addition, BRCA1/2 testing may have direct implications for patients with other types of cancers, many which are now being found to have BRCA1/2 involvement.

  7. Municipal distribution of ovarian cancer mortality in Spain

    Directory of Open Access Journals (Sweden)

    Vidal Enrique

    2008-09-01

    Full Text Available Abstract Background Spain was the country that registered the greatest increases in ovarian cancer mortality in Europe. This study describes the municipal distribution of ovarian cancer mortality in Spain using spatial models for small-area analysis. Methods Smoothed relative risks of ovarian cancer mortality were obtained, using the Besag, York and Molliè autoregressive spatial model. Standardised mortality ratios, smoothed relative risks, and distribution of the posterior probability of relative risks being greater than 1 were depicted on municipal maps. Results During the study period (1989–1998, 13,869 ovarian cancer deaths were registered in 2,718 Spanish towns, accounting for 4% of all cancer-related deaths among women. The highest relative risks were mainly concentrated in three areas, i.e., the interior of Barcelona and Gerona (north-east Spain, the north of Lugo and Asturias (north-west Spain and along the Seville-Huelva boundary (in the south-west. Eivissa (Balearic Islands and El Hierro (Canary Islands also registered increased risks. Conclusion Well established ovarian cancer risk factors might not contribute significantly to the municipal distribution of ovarian cancer mortality. Environmental and occupational exposures possibly linked to this pattern and prevalent in specific regions, are discussed in this paper. Small-area geographical studies are effective instruments for detecting risk areas that may otherwise remain concealed on a more reduced scale.

  8. 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

  9. Hormone-receptor expression and ovarian cancer survival

    DEFF Research Database (Denmark)

    Sieh, Weiva; Köbel, Martin; Longacre, Teri A;

    2013-01-01

    Few biomarkers of ovarian cancer prognosis have been established, partly because subtype-specific associations might be obscured in studies combining all histopathological subtypes. We examined whether tumour expression of the progesterone receptor (PR) and oestrogen receptor (ER) was associated ...

  10. Chlamydia trachomatis Serology in Women with and without Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Roberta B. Ness

    2008-01-01

    Full Text Available Pelvic inflammation has been implicated in the genesis of ovarian cancer. We conducted serologic measurements of Chlamydia trachomatis antibodies as a surrogate marker of chlamydial pelvic inflammatory disease. Women with ovarian cancer (n=521 and population-based controls (n=766 were tested. IgG antibodies to serovar D of chlamydia elementary bodies (EBs were detected using an ELISA assay. The odds of having ovarian cancer among women with the highest titers (≥0.40 OD units were 0.6 (95% CI 0.4–0.9. These data do not support our earlier finding of elevated titers for antibodies to C. trachomatis among women with ovarian cancer.

  11. Combining Chemotherapy with Bevacizumab Improves Outcomes for Ovarian Cancer Patients

    Science.gov (United States)

    Results from two phase III randomized clinical trials suggest that, at least for some patients with ovarian cancer, adding the antiangiogenesis agent bevacizumab to chemotherapy increases the time to disease progression and may improve survival.

  12. What's New in Ovarian Cancer Research and Treatment?

    Science.gov (United States)

    ... escape to close saved articles window. My Saved Articles » My ACS ... new in ovarian cancer research and treatment? Risk factors and causes Scientists continue to study the genes responsible for familial ...

  13. The promise and challenge of ovarian cancer models

    OpenAIRE

    Hasan, Noor; Ohman, Anders W.; Dinulescu, Daniela M.

    2015-01-01

    The complexity and heterogeneity of ovarian cancer cases are difficult to reproduce in in vitro studies, which cannot adequately elucidate the molecular events involved in tumor initiation and disease metastasis. It has now become clear that, although the multiple histological subtypes of ovarian cancer are being treated with similar surgical and therapeutic approaches, they are in fact characterized by distinct phenotypes, cell of origin, and underlying key genetic and genomic alterations. C...

  14. Major clinical research advances in gynecologic cancer in 2015

    Science.gov (United States)

    2016-01-01

    In 2015, fourteen topics were selected as major research advances in gynecologic oncology. For ovarian cancer, high-level evidence for annual screening with multimodal strategy which could reduce ovarian cancer deaths was reported. The best preventive strategies with current status of evidence level were also summarized. Final report of chemotherapy or upfront surgery (CHORUS) trial of neoadjuvant chemotherapy in advanced stage ovarian cancer and individualized therapy based on gene characteristics followed. There was no sign of abating in great interest in immunotherapy as well as targeted therapies in various gynecologic cancers. The fifth Ovarian Cancer Consensus Conference which was held in November 7–9 in Tokyo was briefly introduced. For cervical cancer, update of human papillomavirus vaccines regarding two-dose regimen, 9-valent vaccine, and therapeutic vaccine was reviewed. For corpus cancer, the safety concern of power morcellation in presumed fibroids was explored again with regard to age and prevalence of corpus malignancy. Hormone therapy and endometrial cancer risk, trabectedin as an option for leiomyosarcoma, endometrial cancer and Lynch syndrome, and the radiation therapy guidelines were also discussed. In addition, adjuvant therapy in vulvar cancer and the updated of targeted therapy in gynecologic cancer were addressed. For breast cancer, palbociclib in hormone-receptor-positive advanced disease, oncotype DX Recurrence Score in low-risk patients, regional nodal irradiation to internal mammary, supraclavicular, and axillary lymph nodes, and cavity shave margins were summarized as the last topics covered in this review. PMID:27775259

  15. LOSS OF HETEROZYGOSITY ON CHROMOSOME 17p13.3 IN OVARIAN CANCER AND CERVICAL CANCER

    Institute of Scientific and Technical Information of China (English)

    Zhang Guoling; Yang Huijian; Xu Kaili; Zhou Jin; Qin Ruidi; Lu Minghua

    1998-01-01

    Objective:To identify the loss of heterozygosity (LOH) on chromosome 17p13.3 in ovarian cancer and cervical cancer. Methods: The frequency of LOH on chromosome 17p13.3 in DNA samples from 24 ovarian cancers, 9 cervical cancers, and 13 non-malignant gynecological diseases were determined respectively, using Southern blot method with probe PYNZ.22. Results:LOH on 17p13.3 was found in 12 of 24 (50.0%) ovarian cancers (including a borderline mucinous cystadenoma), 4of 9 (44.4%) cervical carcinomas, and 1 of 13 (7.7%) nonmalignant gynecological diseases, which was cervical intraepithelial neoplasm HI (CIN Ⅲ) (P<0.01).Conclusion: These results show that LOH on 17p13.3 is associated with ovarian cancer and cervical cancer,suggesting that detection of LOH on 17p13.3 may be helpful to understand the molecular pathogenesis of ovarian cancer and cervical cancer.

  16. Metformin against Cancer Stem Cells through the Modulation of Energy Metabolism: Special Considerations on Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Tae Hun Kim

    2014-01-01

    Full Text Available Ovarian cancer is the most lethal gynecologic malignancy among women worldwide and is presumed to result from the presence of ovarian cancer stem cells. To overcome the limitation of current anticancer agents, another anticancer strategy is necessary to effectively target cancer stem cells in ovarian cancer. In many types of malignancies, including ovarian cancer, metformin, one of the most popular antidiabetic drugs, has been demonstrated to exhibit chemopreventive and anticancer efficacy with respect to incidence and overall survival rates. Thus, the metabolic reprogramming of cancer and cancer stem cells driven by genetic alterations during carcinogenesis and cancer progression could be therapeutically targeted. In this review, the potential efficacy and anticancer mechanisms of metformin against ovarian cancer stem cells will be discussed.

  17. Gonadotropin-releasing hormone agonists cotreatment during chemotherapy in borderline ovarian tumor and ovarian cancer patients

    Institute of Scientific and Technical Information of China (English)

    ZHU Hong-lan; WANG Yan; LI Xiao-ping; WANG Chao-hua; WANG Yue; CUI Heng; WANG Jian-liu

    2013-01-01

    Background Recently,conservative surgery is acceptable in young patients with borderline ovarian tumor and ovarian cancer.The preservation of these patients' future fertility has been the focus of recent interest.This study aimed to observe the effect of gonadotropin-releasing hormone agonists (GnRHa) cotreatment during chemotherapy in borderline ovarian tumor and ovarian cancer patients.Methods Sixteen patients who were treated with fertility preservation surgery for borderline ovarian tumor and ovarian cancer and then administered GnRHa during chemotherapy in Peking University People's Hospital from January 2006 to July 2010 were retrospectively analyzed.This group was compared with a control group of 16 women who were treated concurrently with similar chemotherapy (n=5) without GnRHa or were historical controls (n=11).The disease recurrence,the menstruation status and reproductive outcome were followed up and compared between the two groups.Results There were no significant differences between both groups regarding age,body weight,height,marriage status,classification of the tumors,stage of the disease,as were the cumulative doses of each chemotherapeutic agent.One (1/16) patient in the study group while 2 (2/16) patients in the control group relapsed 2 years after conclusion of the primary treatment (P >0.05).All of the 16 women in the study group compared with 11 of the 16 patients in the control group resumed normal menses 6 months after the termination of the treatment (P <0.05).There were 4 spontaneous pregnancies in the study group while 2 in the control group,all of the neonates were healthy.Conclusions GnRHa administration before and during chemotherapy in borderline ovarian tumor and ovarian cancer patients who had undergone fertility preservation operation may bring up higher rates of spontaneous resumption of menses and a better pregnancy rate.Long-term follow up and large scale clinical studies are required.

  18. 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

  19. Mismatch repair and treatment resistance in ovarian cancer

    International Nuclear Information System (INIS)

    The treatment of ovarian cancer is hindered by intrinsic or acquired resistance to platinum-based chemotherapy. The aim of this study is to determine the frequency of mismatch repair (MMR) inactivation in ovarian cancer and its association with resistance to platinum-based chemotherapy. We determined, microsatellite instability (MSI) as a marker for MMR inactivation (analysis of BAT25 and BAT26), MLH1 promoter methylation status (methylation specific PCR on bisulfite treated DNA) and mRNA expression of MLH1, MSH2, MSH3, MSH6 and PMS2 (quantitative RT-PCR) in 75 ovarian carcinomas and eight ovarian cancer cell lines MSI was detected in three of the eight cell lines i.e. A2780 (no MLH1 mRNA expression due to promoter methylation), SKOV3 (no MLH1 mRNA expression) and 2774 (no altered expression of MMR genes). Overall, there was no association between cisplatin response and MMR status in these eight cell lines. Seven of the 75 ovarian carcinomas showed MLH1 promoter methylation, however, none of these showed MSI. Forty-six of these patients received platinum-based chemotherapy (11 non-responders, 34 responders, one unknown response). The resistance seen in the eleven non-responders was not related to MSI and therefore also not to MMR inactivation. No MMR inactivation was detected in 75 ovarian carcinoma specimens and no association was seen between MMR inactivation and resistance in the ovarian cancer cell lines as well as the ovarian carcinomas. In the discussion, the results were compared to that of twenty similar studies in the literature including in total 1315 ovarian cancer patients. Although no association between response and MMR status was seen in the primary tumor the possible role of MMR inactivation in acquired resistance deserves further investigation

  20. Drugs Approved for Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for ovarian cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters. The drug names link to NCI's Cancer Drug Information summaries.

  1. Ovarian cancer: what’s new, where next?

    OpenAIRE

    A Spencer, John

    2003-01-01

    The recent RDOG studies have confirmed the value of CT in the management of ovarian cancer. However we now know that metastases to the ovary may exactly mimic primary cancer. This demands a firm histological diagnosis when surgery is not planned and especially with a history of breast and gastrointestinal tract cancer. CT guided needle biopsy can provide this.

  2. What Are the Risk Factors for Ovarian Cancer?

    Science.gov (United States)

    ... cancer? What are the risk factors for ovarian cancer? A risk factor is anything that changes your chance of getting ... is a risk factor for a number of cancers. But risk factors don't tell us everything. Having a risk ...

  3. Task Force Reaffirms Recommendation against Ovarian Cancer Screening | Division of Cancer Prevention

    Science.gov (United States)

    Women at average risk of ovarian cancer should not be screened for the disease, the U.S. Preventive Services Task Force (USPSTF) has reaffirmed. Published in the Annals of Internal Medicine on September 11, the latest USPSTF clinical guideline does not apply to women who have symptoms of ovarian cancer or who have genetic mutations that increase their risk of ovarian cancer. |

  4. Anti-galectin-3 therapy: a new chance for multiple myeloma and ovarian cancer?

    Science.gov (United States)

    Mirandola, Leonardo; Nguyen, Diane D; Rahman, Rakhshanda L; Grizzi, Fabio; Yuefei, Yu; Figueroa, José A; Jenkins, Marjorie R; Cobos, Everardo; Chiriva-Internati, Maurizio

    2014-10-01

    Here we review the role of Galectins in the molecular pathogenesis of multiple myeloma and ovarian cancer, with a special focus on Glectin-3. Multiple myeloma is the second most common hematologic malignancy worldwide. Because the pathogenesis of multiple myeloma is still incompletely understood, there is no ultimately effective cure, and this cancer results fatal. Ovarian cancer is the most lethal gynecologic malignancy worldwide. Due to the lack of screening techniques for early detection, patients are mostly diagnosed with advanced disease, which results ultimately fatal. Multiple myeloma and ovarian cancer have different biologies, but they share a strong dependence on adhesion with extracellular matrix and other cells. Galectin-3 plays a key role in regulating such adhesive abilities of tumor cells. Here we discuss the outcomes and possible mechanism of action of a truncated, dominant negative form of Galectin-3, Galectin-3C, in these malignancies. Overall, we report that Galectin-3C is a promising new compound for effective adjuvant therapies in advanced, refractory multiple myeloma and ovarian cancer. PMID:24801755

  5. Ovarian cancer susceptibility alleles and risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers.

    Science.gov (United States)

    Ramus, Susan J; Antoniou, Antonis C; Kuchenbaecker, Karoline B; Soucy, Penny; Beesley, Jonathan; Chen, Xiaoqing; McGuffog, Lesley; Sinilnikova, Olga M; Healey, Sue; Barrowdale, Daniel; Lee, Andrew; Thomassen, Mads; Gerdes, Anne-Marie; Kruse, Torben A; Jensen, Uffe Birk; Skytte, Anne-Bine; Caligo, Maria A; Liljegren, Annelie; Lindblom, Annika; Olsson, Håkan; Kristoffersson, Ulf; Stenmark-Askmalm, Marie; Melin, Beatrice; Domchek, Susan M; Nathanson, Katherine L; Rebbeck, Timothy R; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Złowocka, Elżbieta; Gronwald, Jacek; Huzarski, Tomasz; Byrski, Tomasz; Cybulski, Cezary; Toloczko-Grabarek, Aleksandra; Osorio, Ana; Benitez, Javier; Duran, Mercedes; Tejada, Maria-Isabel; Hamann, Ute; Rookus, Matti; van Leeuwen, Flora E; Aalfs, Cora M; Meijers-Heijboer, Hanne E J; van Asperen, Christi J; van Roozendaal, K E P; Hoogerbrugge, Nicoline; Collée, J Margriet; Kriege, Mieke; van der Luijt, Rob B; Peock, Susan; Frost, Debra; Ellis, Steve D; Platte, Radka; Fineberg, Elena; Evans, D Gareth; Lalloo, Fiona; Jacobs, Chris; Eeles, Ros; Adlard, Julian; Davidson, Rosemarie; Eccles, Diana; Cole, Trevor; Cook, Jackie; Paterson, Joan; Douglas, Fiona; Brewer, Carole; Hodgson, Shirley; Morrison, Patrick J; Walker, Lisa; Porteous, Mary E; Kennedy, M John; Pathak, Harsh; Godwin, Andrew K; Stoppa-Lyonnet, Dominique; Caux-Moncoutier, Virginie; de Pauw, Antoine; Gauthier-Villars, Marion; Mazoyer, Sylvie; Léoné, Mélanie; Calender, Alain; Lasset, Christine; Bonadona, Valérie; Hardouin, Agnès; Berthet, Pascaline; Bignon, Yves-Jean; Uhrhammer, Nancy; Faivre, Laurence; Loustalot, Catherine; Buys, Saundra; Daly, Mary; Miron, Alex; Terry, Mary Beth; Chung, Wendy K; John, Esther M; Southey, Melissa; Goldgar, David; Singer, Christian F; Tea, Muy-Kheng; Pfeiler, Georg; Fink-Retter, Anneliese; Hansen, Thomas v O; Ejlertsen, Bent; Johannsson, Oskar Th; Offit, Kenneth; Kirchhoff, Tomas; Gaudet, Mia M; Vijai, Joseph; Robson, Mark; Piedmonte, Marion; Phillips, Kelly-Anne; Van Le, Linda; Hoffman, James S; Ewart Toland, Amanda; Montagna, Marco; Tognazzo, Silvia; Imyanitov, Evgeny; Issacs, Claudine; Janavicius, Ramunas; Lazaro, Conxi; Blanco, Iganacio; Tornero, Eva; Navarro, Matilde; Moysich, Kirsten B; Karlan, Beth Y; Gross, Jenny; Olah, Edith; Vaszko, Tibor; Teo, Soo-Hwang; Ganz, Patricia A; Beattie, Mary S; Dorfling, Cecelia M; van Rensburg, Elizabeth J; Diez, Orland; Kwong, Ava; Schmutzler, Rita K; Wappenschmidt, Barbara; Engel, Christoph; Meindl, Alfons; Ditsch, Nina; Arnold, Norbert; Heidemann, Simone; Niederacher, Dieter; Preisler-Adams, Sabine; Gadzicki, Dorotehea; Varon-Mateeva, Raymonda; Deissler, Helmut; Gehrig, Andrea; Sutter, Christian; Kast, Karin; Fiebig, Britta; Schäfer, Dieter; Caldes, Trinidad; de la Hoya, Miguel; Nevanlinna, Heli; Aittomäki, Kristiina; Plante, Marie; Spurdle, Amanda B; Neuhausen, Susan L; Ding, Yuan Chun; Wang, Xianshu; Lindor, Noralane; Fredericksen, Zachary; Pankratz, V Shane; Peterlongo, Paolo; Manoukian, Siranoush; Peissel, Bernard; Zaffaroni, Daniela; Bonanni, Bernardo; Bernard, Loris; Dolcetti, Riccardo; Papi, Laura; Ottini, Laura; Radice, Paolo; Greene, Mark H; Mai, Phuong L; Andrulis, Irene L; Glendon, Gord; Ozcelik, Hilmi; Pharoah, Paul D P; Gayther, Simon A; Simard, Jacques; Easton, Douglas F; Couch, Fergus J; Chenevix-Trench, Georgia

    2012-04-01

    Germline mutations in BRCA1 and BRCA2 are associated with increased risks of breast and ovarian cancer. A genome-wide association study (GWAS) identified six alleles associated with risk of ovarian cancer for women in the general population. We evaluated four of these loci as potential modifiers of ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Four single-nucleotide polymorphisms (SNPs), rs10088218 (at 8q24), rs2665390 (at 3q25), rs717852 (at 2q31), and rs9303542 (at 17q21), were genotyped in 12,599 BRCA1 and 7,132 BRCA2 carriers, including 2,678 ovarian cancer cases. Associations were evaluated within a retrospective cohort approach. All four loci were associated with ovarian cancer risk in BRCA2 carriers; rs10088218 per-allele hazard ratio (HR) = 0.81 (95% CI: 0.67-0.98) P-trend = 0.033, rs2665390 HR = 1.48 (95% CI: 1.21-1.83) P-trend = 1.8 × 10(-4), rs717852 HR = 1.25 (95% CI: 1.10-1.42) P-trend = 6.6 × 10(-4), rs9303542 HR = 1.16 (95% CI: 1.02-1.33) P-trend = 0.026. Two loci were associated with ovarian cancer risk in BRCA1 carriers; rs10088218 per-allele HR = 0.89 (95% CI: 0.81-0.99) P-trend = 0.029, rs2665390 HR = 1.25 (95% CI: 1.10-1.42) P-trend = 6.1 × 10(-4). The HR estimates for the remaining loci were consistent with odds ratio estimates for the general population. The identification of multiple loci modifying ovarian cancer risk may be useful for counseling women with BRCA1 and BRCA2 mutations regarding their risk of ovarian cancer.

  6. Differential display identifies overexpression of the USP36 gene, encoding a deubiquitinating enzyme, in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Jianduan Li, Lisa M. Olson, Zhengyan Zhang, Lina Li, Miri Bidder, Loan Nguyen, John Pfeifer, Janet S. Rader

    2008-01-01

    Full Text Available Objectives. To find potential diagnostic markers or therapeutic targets, we used differential display technique to identify genes that are over or under expressed in human ovarian cancer. Methods. Genes were initially identified by differential display between two human ovarian surface epithelium cultures and two ovarian cancer cell lines, A2780 and Caov-3. Genes were validated by relative quantitative RT-PCR and RNA in situ hybridization. Results. Twenty-eight non-redundant sequences were expressed differentially in the normal ovarian epithelium and ovarian cancer cell lines. Seven of the 28 sequences showed differential expression between normal ovary and ovarian cancer tissue by RT-PCR. USP36 was over-expressed in ovarian cancer cell lines and tissues by RT-PCR and RNA in situ hybridization. Northern blot analysis and RT-PCR revealed two transcripts for USP36 in ovarian tissue. The major transcript was more specific for ovarian cancer and was detected by RT-PCR in 9/9 ovarian cancer tissues, 3/3 cancerous ascites, 5/14 (36% sera from patients with ovarian cancer, and 0/7 sera from women without ovarian cancer. Conclusion. USP36 is overexpressed in ovarian cancer compared to normal ovary and its transcripts were identified in ascites and serum of ovarian cancer patients.

  7. 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.

  8. Insulin-like growth factor binding protein 2 promotes ovarian cancer cell invasion

    OpenAIRE

    Liu Jinsong; Wang Huamin; Shmulevich Ilya; Mircean Cristian; Lee Eun-Ju; Niemistö Antti; Kavanagh John J; Lee Je-Ho; Zhang Wei

    2005-01-01

    Abstract Background Insulin-like growth factor binding protein 2 (IGFBP2) is overexpressed in ovarian malignant tissues and in the serum and cystic fluid of ovarian cancer patients, suggesting an important role of IGFBP2 in the biology of ovarian cancer. The purpose of this study was to assess the role of increased IGFBP2 in ovarian cancer cells. Results Using western blotting and tissue microarray analyses, we showed that IGFBP2 was frequently overexpressed in ovarian carcinomas compared wit...

  9. Prevalence and contribution of BRCA1 mutations in breast cancer and ovarian cancer: Results from three US population-based case-control studies of ovarian cancer

    Energy Technology Data Exchange (ETDEWEB)

    Whittemore, A.S.; Gong, G.; Itnyre, J. [Stanford Univ. School of Medicine, CA (United States)

    1997-03-01

    We investigate the familial risks of cancers of the breast and ovary, using data pooled from three population-based case-control studies of ovarian cancer that were conducted in the United States. We base estimates of the frequency of mutations of BRCA1 (and possibly other genes) on the reported occurrence of breast cancer and ovarian cancer in the mothers and sisters of 922 women with incident ovarian cancer (cases) and in 922 women with no history of ovarian cancer (controls). Segregation analysis and goodness-of-fit testing of genetic models suggest that rare mutations (frequency .0014; 95% confidence interval .0002-.011) account for all the observed aggregation of breast cancer and ovarian cancer in these families. The estimated risk of breast cancer by age 80 years is 73.5% in mutation carriers and 6.8% in noncarriers. The corresponding estimates for ovarian cancer are 27.8% in carriers and 1.8% in noncarriers. For cancer risk in carriers, these estimates are lower than those obtained from families selected for high cancer prevalence. The estimated proportion of all U.S. cancer diagnoses, by age 80 years, that are due to germ-line BRCA1 mutations is 3.0% for breast cancer and 4.4% for ovarian cancer. Aggregation of breast cancer and ovarian cancer was less evident in the families of 169 cases with borderline ovarian cancers than in the families of cases with invasive cancers. Familial aggregation did not differ by the ethnicity of the probands, although the number of non-White and Hispanic cases (N = 99) was sparse. 14 refs., 3 figs., 6 tabs.

  10. Ovarian Cancer Proteomic, Phosphoproteomic, and Glycoproteomic Data Released - Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    National Cancer Institute (NCI) Clinical Proteomic Tumor Analysis Consortium (CPTAC) scientists have just released a comprehensive dataset of the proteomic analysis of high grade serous ovarian tumor samples,

  11. 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...

  12. 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...

  13. 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...

  14. Genetic changes in nonepithelial ovarian cancer.

    Science.gov (United States)

    Van Nieuwenhuysen, Els; Lambrechts, Sandrina; Lambrechts, Diether; Leunen, Karin; Amant, Frédéric; Vergote, Ignace

    2013-07-01

    Nonepithelial ovarian cancers (OCs), including sex cord-stromal tumors (SCSTs) and germ cell tumors (GCTs), are an uncommon subset of OC, together accounting for 10% of all OCs. The etiology of these tumors remains largely unresolved. It is well established that tumorigenesis is the result of multiple genetic alterations driving a normal cell toward a malignant state. Much effort has been made into researching the molecular mechanisms underlying epithelial OC, but far less is known about the genetic changes in SCSTs and GCTs. Recently, a single point missense mutation (C134W) was found in the FOXL2 gene in approximately 95% of adult-type granulosa cell tumors, suggesting a key role for FOXL2 in these tumors. By contrast, the FOXL2 mutation was not found in the juvenile type. DICER1 somatic missense mutations were found in approximately 60% of Sertoli-Leydig tumors. Ovarian GCTs share many morphological features and a similar pattern of chromosomal alterations with testicular GCTs. In the latter, recent genome-wide association studies have identified seven susceptibility loci near KITLG, SPRY4, UKC2, BAK1, DMRT1, TERT and ATF7IP. All of the susceptibility loci detected thus far are all involved in primordial germ cell function or sex determination. TGF-β/BMP and Wnt/β-catenin signaling was absent in dysgerminomas, but present in yolk sac tumors, suggesting intertumoral heterogeneity. In this article, the authors aim to provide an overview of the current knowledge on the possible molecular changes in SCSTs and GCTs of the ovary. PMID:23875665

  15. Active and passive smoking and risk of ovarian cancer.

    OpenAIRE

    Baker, J. A.; Odunuga, O. O.; Rodabaugh, K J; Reid, M.E.; Menezes, R. J.; Moysich, K B

    2009-01-01

    Cancer epidemiologyCancer type:ovarian cancerStudy design:case-controlStudy size:434 cases, 868 controlsDescription of cohort(s) studied:434 women with promary epithelial ovarian, peritoneal, fallopian tube cancer, 868 women randomly selectedExposure(s) evaluated:ETSConfounders controlled for:smoking habitsImpact on risk: nonsmokers with ETS EXPOSURE, OR 0.68, 95%CI 0.47-0.99Current smokers with ETS exposure, OR 0.5, 95% CI 0.34-0.9Never smokres with ETS exposure, OR 0.39, 95% CI 0.1-1.48, P=...

  16. The preclinical natural history of serous ovarian cancer: defining the target for early detection.

    Directory of Open Access Journals (Sweden)

    Patrick O Brown

    2009-07-01

    Full Text Available BACKGROUND: Ovarian cancer kills approximately 15,000 women in the United States every year, and more than 140,000 women worldwide. Most deaths from ovarian cancer are caused by tumors of the serous histological type, which are rarely diagnosed before the cancer has spread. Rational design of a potentially life-saving early detection and intervention strategy requires understanding the lesions we must detect in order to prevent lethal progression. Little is known about the natural history of lethal serous ovarian cancers before they become clinically apparent. We can learn about this occult period by studying the unsuspected serous cancers that are discovered in a small fraction of apparently healthy women who undergo prophylactic bilateral salpingo-oophorectomy (PBSO. METHODS AND FINDINGS: We developed models for the growth, progression, and detection of occult serous cancers on the basis of a comprehensive analysis of published data on serous cancers discovered by PBSO in BRCA1 mutation carriers. Our analysis yielded several critical insights into the early natural history of serous ovarian cancer. First, these cancers spend on average more than 4 y as in situ, stage I, or stage II cancers and approximately 1 y as stage III or IV cancers before they become clinically apparent. Second, for most of the occult period, serous cancers are less than 1 cm in diameter, and not visible on gross examination of the ovaries and Fallopian tubes. Third, the median diameter of a serous ovarian cancer when it progresses to an advanced stage (stage III or IV is about 3 cm. Fourth, to achieve 50% sensitivity in detecting tumors before they advance to stage III, an annual screen would need to detect tumors of 1.3 cm in diameter; 80% detection sensitivity would require detecting tumors less than 0.4 cm in diameter. Fifth, to achieve a 50% reduction in serous ovarian cancer mortality with an annual screen, a test would need to detect tumors of 0.5 cm in diameter

  17. Whole-genome characterization of chemoresistant ovarian cancer.

    Science.gov (United States)

    Patch, Ann-Marie; Christie, Elizabeth L; Etemadmoghadam, Dariush; Garsed, Dale W; George, Joshy; Fereday, Sian; Nones, Katia; Cowin, Prue; Alsop, Kathryn; Bailey, Peter J; Kassahn, Karin S; Newell, Felicity; Quinn, Michael C J; Kazakoff, Stephen; Quek, Kelly; Wilhelm-Benartzi, Charlotte; Curry, Ed; Leong, Huei San; Hamilton, Anne; Mileshkin, Linda; Au-Yeung, George; Kennedy, Catherine; Hung, Jillian; Chiew, Yoke-Eng; Harnett, Paul; Friedlander, Michael; Quinn, Michael; Pyman, Jan; Cordner, Stephen; O'Brien, Patricia; Leditschke, Jodie; Young, Greg; Strachan, Kate; Waring, Paul; Azar, Walid; Mitchell, Chris; Traficante, Nadia; Hendley, Joy; Thorne, Heather; Shackleton, Mark; Miller, David K; Arnau, Gisela Mir; Tothill, Richard W; Holloway, Timothy P; Semple, Timothy; Harliwong, Ivon; Nourse, Craig; Nourbakhsh, Ehsan; Manning, Suzanne; Idrisoglu, Senel; Bruxner, Timothy J C; Christ, Angelika N; Poudel, Barsha; Holmes, Oliver; Anderson, Matthew; Leonard, Conrad; Lonie, Andrew; Hall, Nathan; Wood, Scott; Taylor, Darrin F; Xu, Qinying; Fink, J Lynn; Waddell, Nick; Drapkin, Ronny; Stronach, Euan; Gabra, Hani; Brown, Robert; Jewell, Andrea; Nagaraj, Shivashankar H; Markham, Emma; Wilson, Peter J; Ellul, Jason; McNally, Orla; Doyle, Maria A; Vedururu, Ravikiran; Stewart, Collin; Lengyel, Ernst; Pearson, John V; Waddell, Nicola; deFazio, Anna; Grimmond, Sean M; Bowtell, David D L

    2015-05-28

    Patients with high-grade serous ovarian cancer (HGSC) have experienced little improvement in overall survival, and standard treatment has not advanced beyond platinum-based combination chemotherapy, during the past 30 years. To understand the drivers of clinical phenotypes better, here we use whole-genome sequencing of tumour and germline DNA samples from 92 patients with primary refractory, resistant, sensitive and matched acquired resistant disease. We show that gene breakage commonly inactivates the tumour suppressors RB1, NF1, RAD51B and PTEN in HGSC, and contributes to acquired chemotherapy resistance. CCNE1 amplification was common in primary resistant and refractory disease. We observed several molecular events associated with acquired resistance, including multiple independent reversions of germline BRCA1 or BRCA2 mutations in individual patients, loss of BRCA1 promoter methylation, an alteration in molecular subtype, and recurrent promoter fusion associated with overexpression of the drug efflux pump MDR1. PMID:26017449

  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. Serous ovarian, fallopian tube and primary peritoneal cancers

    DEFF Research Database (Denmark)

    Sørensen, Rie D; Schnack, Tine H; Karlsen, Mona A;

    2015-01-01

    OBJECTIVE: The aim of this systematic review is to analyze data on risk factors, epidemiology, clinicopathology and molecular biology from studies comparing primary peritoneal cancer, fallopian tube cancer and ovarian cancer of serous histology, in order to achieve a greater understanding...... of whether or not these disorders should be considered as separate entities. METHODS: A systematic literature search was conducted in PubMed and MEDLINE. Case-control studies comparing primary serous peritoneal or fallopian tube carcinomas with primary serous ovarian carcinomas or a control group were...... included. RESULTS: Twenty-eight studies were found eligible. Primary peritoneal cancer patients were older, had higher parity, were more often obese and had poorer survival compared to ovarian cancer patients. Differences in protein expression patterns of Her2/neu, estrogen and progestin receptors...

  20. Will Chinese ovarian cancer patients benefit from knowing the BRCA2 mutation status?

    Institute of Scientific and Technical Information of China (English)

    Guo-Yan Liu; Wei Zhang

    2012-01-01

    In Western countries,the mutation status of the BRCA1 and BRCA2 genes is commonly determined for genetic counseling among members of families with a history of breast or ovarian cancer,especially for women of the Ashkenazi Jewish ethnicity.Recent studies in the Cancer Genome Atlas project have demonstrated that BRCA2 mutation carriers are more responsive to platinum-based chemotherapy among high-grade serous ovarian cancer patients.Thus,in Western countries,the mutation status of BRCA1 and BRCA2 is recognized to have an important value with which to assess cancer risk and therapeutic response.However,very limited studies of BRCA1 and BRCA2 mutations and their implications for counseling and therapeutic prediction have been conducted in China.Therefore,a potentially important genetic test that is technically simple has not benefited Chinese women with an increased risk of breast or ovarian cancer.This article summarizes the current progress in the study of BRCA1/2 mutation in China and recommends an increased effort in applying advances in genetic testing to the clinical management of Chinese patients with ovarian cancer.

  1. 二甲双胍联合 TC 方案治疗晚期卵巢癌的临床观察%Clinical Observations on Metformin United TC Scheme in Advanced Ovarian Cancer

    Institute of Scientific and Technical Information of China (English)

    慈晓华; 庄静; 冯福斌; 孙月; 马家栋; 孙长岗

    2015-01-01

    目的:分析比较二甲双胍联合TC方案和单纯TC方案在伴有糖尿病的中老年晚期卵巢癌患者术后辅助化疗中的临床疗效。方法60例伴有糖尿病的中老年晚期卵巢癌患者,均用胰岛素控制血糖良好,随机分为治疗组和对照组,每组30例,治疗组采用二甲双胍联合TC方案治疗,对照组采用TC方案治疗。两组患者治疗均以21 d为1个周期。至少完成2周期化疗的患者进行疗效、毒副反应评价。结果治疗组的临床疗效优于对照组,治疗组有效28例(93.3%);对照组有效19例(63.3%)。两组比较,差异具有统计学意义( P<0.05)。两组的副反应相比,差异无统计学意义( P>0.05)。结论采用二甲双胍联合TC方案治疗伴糖尿病的中老年人晚期卵巢癌的临床疗效确切,不良反应并未明显增加,值得在临床推广应用。%[ ABSTRACT ] Objective To compare the clinical effect in assistant chemotherapy of metformin united TC scheme and alone TC scheme in elderly patients suffering from advanced ovarian cancer and diabetes.Methods Sixty elderly patients suffering from advanced ovarian cancer and diabetes,all with insulin to control blood sugar well,random-ly were divided into treatment group and control group.The treatment group were treated with metformin united TC scheme,the control group with TC scheme only.Twenty-one days as a treatment cycle.the efficacy and side effects in pa-tients at least two cycles of chemotherapy were evaluated.Results The clinical efficacy of the treatment group is better than the control group.There are twenty-eight cases of effective in the treatment group and the effective rate is 93.3%. There are nineteen cases of effective in the control group and the effective rate is 63 .3%,the effective rate were statisti-cally significant(P0.05).Conclusion The clinical effi-cacy of treatment with metformin united TC program in elderly patients suffering

  2. An epigenetic signature in peripheral blood predicts active ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Andrew E Teschendorff

    Full Text Available BACKGROUND: Recent studies have shown that DNA methylation (DNAm markers in peripheral blood may hold promise as diagnostic or early detection/risk markers for epithelial cancers. However, to date no study has evaluated the diagnostic and predictive potential of such markers in a large case control cohort and on a genome-wide basis. PRINCIPAL FINDINGS: By performing genome-wide DNAm profiling of a large ovarian cancer case control cohort, we here demonstrate that active ovarian cancer has a significant impact on the DNAm pattern in peripheral blood. Specifically, by measuring the methylation levels of over 27,000 CpGs in blood cells from 148 healthy individuals and 113 age-matched pre-treatment ovarian cancer cases, we derive a DNAm signature that can predict the presence of active ovarian cancer in blind test sets with an AUC of 0.8 (95% CI (0.74-0.87. We further validate our findings in another independent set of 122 post-treatment cases (AUC = 0.76 (0.72-0.81. In addition, we provide evidence for a significant number of candidate risk or early detection markers for ovarian cancer. Furthermore, by comparing the pattern of methylation with gene expression data from major blood cell types, we here demonstrate that age and cancer elicit common changes in the composition of peripheral blood, with a myeloid skewing that increases with age and which is further aggravated in the presence of ovarian cancer. Finally, we show that most cancer and age associated methylation variability is found at CpGs located outside of CpG islands. SIGNIFICANCE: Our results underscore the potential of DNAm profiling in peripheral blood as a tool for detection or risk-prediction of epithelial cancers, and warrants further in-depth and higher CpG coverage studies to further elucidate this role.

  3. 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

  4. Mass Spectrometric Screening of Ovarian Cancer with Serum Glycans

    Directory of Open Access Journals (Sweden)

    Jae-Han Kim

    2014-01-01

    Full Text Available Changes of glycosylation pattern in serum proteins have been linked to various diseases including cancer, suggesting possible development of novel biomarkers based on the glycomic analysis. In this study, N-linked glycans from human serum were quantitatively profiled by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF mass spectrometry (MS and compared between healthy controls and ovarian cancer patients. A training set consisting of 40 healthy controls and 40 ovarian cancer cases demonstrated an inverse correlation between P value of ANOVA and area under the curve (AUC of each candidate biomarker peak from MALDI-TOF MS, providing standards for the classification. A multibiomarker panel composed of 15 MALDI-TOF MS peaks resulted in AUC of 0.89, 80~90% sensitivity, and 70~83% specificity in the training set. The performance of the biomarker panel was validated in a separate blind test set composed of 23 healthy controls and 37 ovarian cancer patients, leading to 81~84% sensitivity and 83% specificity with cut-off values determined by the training set. Sensitivity of CA-125, the most widely used ovarian cancer marker, was 74% in the training set and 78% in the test set, respectively. These results indicate that MALDI-TOF MS-mediated serum N-glycan analysis could provide critical information for the screening of ovarian cancer.

  5. 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

  6. 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....

  7. Clinical relevance of circulating cell-free microRNAs in ovarian cancer.

    Science.gov (United States)

    Nakamura, Koji; Sawada, Kenjiro; Yoshimura, Akihiko; Kinose, Yasuto; Nakatsuka, Erika; Kimura, Tadashi

    2016-01-01

    Ovarian cancer is the leading cause of death among gynecologic malignancies. Since ovarian cancer develops asymptomatically, it is often diagnosed at an advanced and incurable stage. Despite many years of research, there is still a lack of reliable diagnostic markers and methods for early detection and screening. Recently, it was discovered that cell-free microRNAs (miRNAs) circulate in the body fluids of healthy and diseased patients, suggesting that they may serve as a novel diagnostic marker. This review summarizes the current knowledge regarding the potential clinical relevance of circulating cell-free miRNA for ovarian cancer diagnosis, prognosis, and therapeutics. Despite the high levels of ribonucleases in many types of body fluids, most of the circulating miRNAs are packaged in microvesicles, exosomes, or apoptotic bodies, are binding to RNA-binding protein such as argonaute 2 or lipoprotein complexes, and are thus highly stable. Cell-free miRNA signatures are known to be parallel to those from the originating tumor cells, indicating that circulating miRNA profiles accurately reflect the tumor profiles. Since it is well established that the dysregulation of miRNAs is involved in the tumorigenesis of ovarian cancer, cell-free miRNAs circulating in body fluids such as serum, plasma, whole blood, and urine may reflect not only the existence of ovarian cancer but also tumor histology, stage, and prognoses of the patients. Several groups have successfully demonstrated that serum or plasma miRNAs are able to discriminate patients with ovarian cancer patients from healthy controls, suggesting that the addition of these miRNAs to current testing regimens may improve diagnosis accuracies for ovarian cancer. Furthermore, recent studies have revealed that changes in levels of cell-free circulating miRNAs are associated with the condition of cancer patients. Discrepancies between the results across studies due to the lack of an established endogenous miRNA control to

  8. Ovarian cancer, the coagulation pathway, and inflammation.

    Science.gov (United States)

    Wang, Xipeng; Wang, Ena; Kavanagh, John J; Freedman, Ralph S

    2005-06-21

    Epithelial ovarian cancer (EOC) represents the most frequent cause of death in the United States from a cancer involving the female genital tract. Contributing to the overall poor outcome in EOC patients, are the metastases to the peritoneum and stroma that are common in this cancer. In one study, cDNA microarray analysis was performed on fresh tissue to profile gene expression in patients with EOC. This study showed a number of genes with significantly altered expression in the pelvic peritoneum and stroma, and in the vicinity of EOC implants. These genes included those encoding coagulation factors and regulatory proteins in the coagulation cascade and genes encoding proteins associated with inflammatory responses. In addition to promoting the formation of blood clots, coagulation factors exhibit many other biologic functions as well as tumorigenic functions, the later including tumor cell proliferation, angiogenesis, invasion, and metastasis. Coagulation pathway proteins involved in tumorigenesis consist of factor II (thrombin), thrombin receptor (protease-activated receptors), factor III (tissue factor), factor VII, factor X and factor I (fibrinogen), and fibrin and factor XIII. In a recent study we conducted, we found that factor XII, factor XI, and several coagulation regulatory proteins, including heparin cofactor-II and epithelial protein C receptor (EPCR), were also upregulated in the peritoneum of EOC. In this review, we summarize evidence in support of a role for these factors in promoting tumor cell progression and the formation of ascites. We also discuss the different roles of coagulation factor pathways in the tumor and peritumoral microenvironments as they relate to angiogenesis, proliferation, invasion, and metastasis. Since inflammatory responses are another characteristic of the peritoneum in EOC, we also discuss the linkage between the coagulation cascade and the cytokines/chemokines involved in inflammation. Interleukin-8, which is considered an

  9. Ovarian cancer, the coagulation pathway, and inflammation

    Directory of Open Access Journals (Sweden)

    Kavanagh John J

    2005-06-01

    Full Text Available Abstract Epithelial ovarian cancer (EOC represents the most frequent cause of death in the United States from a cancer involving the female genital tract. Contributing to the overall poor outcome in EOC patients, are the metastases to the peritoneum and stroma that are common in this cancer. In one study, cDNA microarray analysis was performed on fresh tissue to profile gene expression in patients with EOC. This study showed a number of genes with significantly altered expression in the pelvic peritoneum and stroma, and in the vicinity of EOC implants. These genes included those encoding coagulation factors and regulatory proteins in the coagulation cascade and genes encoding proteins associated with inflammatory responses. In addition to promoting the formation of blood clots, coagulation factors exhibit many other biologic functions as well as tumorigenic functions, the later including tumor cell proliferation, angiogenesis, invasion, and metastasis. Coagulation pathway proteins involved in tumorigenesis consist of factor II (thrombin, thrombin receptor (protease-activated receptors, factor III (tissue factor, factor VII, factor X and factor I (fibrinogen, and fibrin and factor XIII. In a recent study we conducted, we found that factor XII, factor XI, and several coagulation regulatory proteins, including heparin cofactor-II and epithelial protein C receptor (EPCR, were also upregulated in the peritoneum of EOC. In this review, we summarize evidence in support of a role for these factors in promoting tumor cell progression and the formation of ascites. We also discuss the different roles of coagulation factor pathways in the tumor and peritumoral microenvironments as they relate to angiogenesis, proliferation, invasion, and metastasis. . Since inflammatory responses are another characteristic of the peritoneum in EOC, we also discuss the linkage between the coagulation cascade and the cytokines/chemokines involved in inflammation. Interleukin

  10. Krukenberg tumors diagnosed during pregnancy simultaneously with advanced gastric cancer; A case report

    International Nuclear Information System (INIS)

    Krukenberg tumors recognized during pregnancy are rarely reported. The preoperative diagnosis can be challenging because of the confusing morphological features and symptoms during pregnancy. Here, we report a case of a 29-year-old pregnant woman at 29 weeks gestation presenting with bilateral solid ovarian masses, which were later diagnosed as metastatic ovarian cancer originating from advanced gastric cancer. This case suggests that Krukenberg tumors should be considered when bilateral ovarian solid masses are encountered regardless of pregnancy

  11. Krukenberg tumors diagnosed during pregnancy simultaneously with advanced gastric cancer; A case report

    Energy Technology Data Exchange (ETDEWEB)

    You, Myung Won; Jung, Yoon Young; Shin, Jung Hwan; Hong, Young Ok [Eulji Hospital, Eulji University School of Medicine, Seoul (Korea, Republic of)

    2015-06-15

    Krukenberg tumors recognized during pregnancy are rarely reported. The preoperative diagnosis can be challenging because of the confusing morphological features and symptoms during pregnancy. Here, we report a case of a 29-year-old pregnant woman at 29 weeks gestation presenting with bilateral solid ovarian masses, which were later diagnosed as metastatic ovarian cancer originating from advanced gastric cancer. This case suggests that Krukenberg tumors should be considered when bilateral ovarian solid masses are encountered regardless of pregnancy.

  12. Isolated Axillary Lymph Node Metastasis from Serous Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Hemant Goyal

    2012-01-01

    Full Text Available A 68-year-old female with past medical history of stage IIIc serous ovarian cancer after cytoreductive surgery and adjuvant chemotherapy came to clinic for regular follow-up visit. Physical examination was completely normal except for an isolated left axillary lymph node enlargement. Patient's abdominal sonogram and CT scan of abdomen and pelvis did not show any other new metastasis. Surgical excisional biopsy of the lymph node was performed and pathology revealed features of metastatic serous ovarian carcinoma.

  13. 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

  14. Comparison of candidate serologic markers for type I and type II ovarian cancer

    DEFF Research Database (Denmark)

    Lu, Dan; Kuhn, Elisabetta; Bristow, Robert E;

    2011-01-01

    To examine the value of individual and combinations of ovarian cancer associated blood biomarkers for the discrimination between plasma of patients with type I or II ovarian cancer and disease-free volunteers.......To examine the value of individual and combinations of ovarian cancer associated blood biomarkers for the discrimination between plasma of patients with type I or II ovarian cancer and disease-free volunteers....

  15. Implementing rapid, robust, cost-effective, patient-centred, routine genetic testing in ovarian cancer patients.

    Science.gov (United States)

    George, Angela; Riddell, Daniel; Seal, Sheila; Talukdar, Sabrina; Mahamdallie, Shazia; Ruark, Elise; Cloke, Victoria; Slade, Ingrid; Kemp, Zoe; Gore, Martin; Strydom, Ann; Banerjee, Susana; Hanson, Helen; Rahman, Nazneen

    2016-01-01

    Advances in DNA sequencing have made genetic testing fast and affordable, but limitations of testing processes are impeding realisation of patient benefits. Ovarian cancer exemplifies the potential value of genetic testing and the shortcomings of current pathways to access testing. Approximately 15% of ovarian cancer patients have a germline BRCA1 or BRCA2 mutation which has substantial implications for their personal management and that of their relatives. Unfortunately, in most countries, routine implementation of BRCA testing for ovarian cancer patients has been inconsistent and largely unsuccessful. We developed a rapid, robust, mainstream genetic testing pathway in which testing is undertaken by the trained cancer team with cascade testing to relatives performed by the genetics team. 207 women with ovarian cancer were offered testing through the mainstream pathway. All accepted. 33 (16%) had a BRCA mutation. The result informed management of 79% (121/154) women with active disease. Patient and clinician feedback was very positive. The pathway offers a 4-fold reduction in time and 13-fold reduction in resource requirement compared to the conventional testing pathway. The mainstream genetic testing pathway we present is effective, efficient and patient-centred. It can deliver rapid, robust, large-scale, cost-effective genetic testing of BRCA1 and BRCA2 and may serve as an exemplar for other genes and other diseases. PMID:27406733

  16. Implementing rapid, robust, cost-effective, patient-centred, routine genetic testing in ovarian cancer patients.

    Science.gov (United States)

    George, Angela; Riddell, Daniel; Seal, Sheila; Talukdar, Sabrina; Mahamdallie, Shazia; Ruark, Elise; Cloke, Victoria; Slade, Ingrid; Kemp, Zoe; Gore, Martin; Strydom, Ann; Banerjee, Susana; Hanson, Helen; Rahman, Nazneen

    2016-07-13

    Advances in DNA sequencing have made genetic testing fast and affordable, but limitations of testing processes are impeding realisation of patient benefits. Ovarian cancer exemplifies the potential value of genetic testing and the shortcomings of current pathways to access testing. Approximately 15% of ovarian cancer patients have a germline BRCA1 or BRCA2 mutation which has substantial implications for their personal management and that of their relatives. Unfortunately, in most countries, routine implementation of BRCA testing for ovarian cancer patients has been inconsistent and largely unsuccessful. We developed a rapid, robust, mainstream genetic testing pathway in which testing is undertaken by the trained cancer team with cascade testing to relatives performed by the genetics team. 207 women with ovarian cancer were offered testing through the mainstream pathway. All accepted. 33 (16%) had a BRCA mutation. The result informed management of 79% (121/154) women with active disease. Patient and clinician feedback was very positive. The pathway offers a 4-fold reduction in time and 13-fold reduction in resource requirement compared to the conventional testing pathway. The mainstream genetic testing pathway we present is effective, efficient and patient-centred. It can deliver rapid, robust, large-scale, cost-effective genetic testing of BRCA1 and BRCA2 and may serve as an exemplar for other genes and other diseases.

  17. 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

  18. 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.

  19. Clear cell ovarian cancer and endometriosis: is there a relationship?

    Science.gov (United States)

    Suzin, Jacek; Obirek, Katarzyna; Sochacka, Amanda; Łoszakiewicz, Marta

    2016-01-01

    Introduction Ovarian clear cell carcinoma is a rare type of ovarian cancer. In recent years, issues of the common genetic origin of endometriosis and ovarian clear cell carcinoma have been raised. Aim of this study Aim of this study was to evaluate the prevalence of this type of cancer, risk factors, prognosis and its potential aetiological association with endometriosis. Material and methods In a retrospective study, we analysed histopathological data of patients operated in the First Department of Gynaecology and Obstetrics (MU, Lodz) due to ovarian cancer in 2004-2014. Among the 394 patients operated on for ovarian cancer, clear cell carcinoma was found in 0.02% (9/394). Menstrual history, parity, comorbidities, data from physical examination, operational protocols and histopathological diagnoses were analysed. Follow-up was obtained from 77.8% of patients. Statistical analysis was performed using Microsoft Excel 2013. Results The mean age of patients at diagnosis was 57.6 years; the BMI in the study group was 27.2; the majority of patients were multiparous (77.8%). Clear cell carcinoma was detected mostly at stage Ia (n = 4). The concentration of Ca125 in the study group had an average of 142.75 U/ml and a median of 69.3 U/ml. The coexistence of endometriosis could not be clinically or histologically confirmed amongst our patients. The most common comorbidity in the study group was hypertension. Conclusions In our clinical material, ovarian clear cell carcinoma is a rare histopathological specimen with a prognostic value comparable to that of serous ovarian cancer. Due to the rarity of this histopathological subtype, proving a cause-and-effect relationship between it and endometriosis can only be elucidated through statistical studies of the entire population.

  20. A KRAS-variant in ovarian cancer acts as a genetic marker of cancer risk.

    Science.gov (United States)

    Ratner, Elena; Lu, Lingeng; Boeke, Marta; Barnett, Rachel; Nallur, Sunitha; Chin, Lena J; Pelletier, Cory; Blitzblau, Rachel; Tassi, Renata; Paranjape, Trupti; Hui, Pei; Godwin, Andrew K; Yu, Herbert; Risch, Harvey; Rutherford, Thomas; Schwartz, Peter; Santin, Alessandro; Matloff, Ellen; Zelterman, Daniel; Slack, Frank J; Weidhaas, Joanne B

    2010-08-15

    Ovarian cancer (OC) is the single most deadly form of women's cancer, typically presenting as an advanced disease at diagnosis in part due to a lack of known risk factors or genetic markers of risk. The KRAS oncogene and altered levels of the microRNA (miRNA) let-7 are associated with an increased risk of developing solid tumors. In this study, we investigated a hypothesized association between an increased risk of OC and a variant allele of KRAS at rs61764370, referred to as the KRAS-variant, which disrupts a let-7 miRNA binding site in this oncogene. Specimens obtained were tested for the presence of the KRAS-variant from nonselected OC patients in three independent cohorts, two independent ovarian case-control studies, and OC patients with hereditary breast and ovarian cancer syndrome (HBOC) as well as their family members. Our results indicate that the KRAS-variant is associated with more than 25% of nonselected OC cases. Further, we found that it is a marker for a significant increased risk of developing OC, as confirmed by two independent case-control analyses. Lastly, we determined that the KRAS-variant was present in 61% of HBOC patients without BRCA1 or BRCA2 mutations, previously considered uninformative, as well as in their family members with cancer. Our findings strongly support the hypothesis that the KRAS-variant is a genetic marker for increased risk of developing OC, and they suggest that the KRAS-variant may be a new genetic marker of cancer risk for HBOC families without other known genetic abnormalities. PMID:20647319

  1. Ovarian cancer stem cells: Can targeted therapy lead to improved progression-free survival?

    Institute of Scientific and Technical Information of China (English)

    Christen; L; Walters; Haygood; Rebecca; C; Arend; J; Michael; Straughn; Donald; J; Buchsbaum

    2014-01-01

    Despite significant effort and research funds, epithelial ovarian cancer remains a very deadly disease. There are no effective screening methods that discover early stage disease; the majority of patients are diagnosed with advanced disease. Treatment modalities consist primarily of radical debulking surgery followed by taxane and platinum-based chemotherapy. Newer therapies including limited targeted agents and intraperitoneal delivery of chemotherapeutic drugs have improved disease-free intervals, but failed to yield longlasting cures in most patients. Chemotherapeutic resistance, particularly in the recurrent setting, plagues the disease. Targeting the pathways and mechanisms behind the development of chemoresistance in ovarian cancer could lead to significant improvement in patient outcomes. In many malignancies, including blood and other solid tumors, there is a subgroup of tumor cells, separate from the bulk population, called cancer stem cells(CSCs). These CSCs are thought to be the cause of metastasis, recurrence and resistance. However, todate, ovarian CSCs have been difficult to identify, isolate, and target. It is felt by many investigators that finding a putative ovarian CSC and a chemotherapeutic agent to target it could be the key to a cure for this deadly disease. This review will focus on recent advances in this arena and discuss some of the controversies surrounding the concept.

  2. Dietary energy balance modulates ovarian cancer progression and metastasis.

    Science.gov (United States)

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

    2014-08-15

    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 surface epithelial ID8 cancer cells. Tumor evaluation revealed that mice group on HED displayed the most extensive tumor formation with the highest tumor score at all organ sites (diaphragm, peritoneum, bowel, liver, kidney, spleen), accompanied with increased levels of insulin, leptin, insulin growth factor-1 (IGF-1), monocyte chemoattractant protein-1 (MCP-1), VEGF and interleukin 6 (IL-6). On the other hand, the mice group on CRD exhibited the least tumor burden associated with a significant reduction in levels of insulin, IGF-1, leptin, MCP-1, VEGF and IL-6. Immunohistochemistry analysis of tumors from HED mice showed higher activation of Akt and mTOR with decreased adenosine monophosphate activated kinase (AMPK) and SIRT1 activation, while tumors from the CRD group exhibited the reverse profile. In conclusion, ovarian cancer growth and metastasis occurred more aggressively under HED conditions and was significantly curtailed under CRD. The suggested mechanism involves modulated secretion of growth factors, cytokines and altered regulation of AMPK and SIRT1 that converges on mTOR inhibition. While the role of a high energy state in ovarian cancer has not been confirnmed in the literature, the current findings support investigating the potential impact of diet modulation as adjunct to other anticancer therapies and as possible individualized treatment strategy of epithelial ovarian cancer.

  3. 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.

  4. Long-term results of a randomized trial comparing cisplatin with cisplatin and cyclophosphamide with cisplatin, cyclophosphamide, and adriamycin in advanced ovarian cancer. GICOG (Gruppo Interregionale Cooperativo Oncologico Ginecologia), Italy.

    Science.gov (United States)

    1992-05-01

    We report the long-term results of a randomized trial comparing cisplatin (P) with cisplatin and cyclophosphamide (CP) with cisplatin, cyclophosphamide, and adriamycin (CAP) in advanced ovarian cancer. Overall, this update confirms previously published data on 529 cases. Median survival times for the three treatments--CAP, CP, and P--are, respectively, 23, 20, and 19 months. The differences among the three arms are still nonsignificant and the estimated percentage survival at 7 years and confidence limits are, respectively, 21.7 (14.9-28.4), 17.0 (11.0-22.9), and 12.2 (6.9-17.4). According to the results of the Cox regression model on prognostic factors, higher grading, a larger residual tumor size, and performance status less than 80 (Karnovsky) all were independently associated with a poorer outcome, while a serous histotype was related to a better prognosis. The other variables (age, stage, center, type of surgery) initially included in the model did not appear to be significantly related to prognosis. The implications of these long-terms results relative to the application of combination chemotherapy with CAP or CP are discussed.

  5. 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.

  6. Ovarian cancer in an interdisciplinary context

    DEFF Research Database (Denmark)

    Seibæk, Lene

    quality of treatment.   Patients/ Methods We developed an interdisciplinary programme including patient data from the records of doctors, nurses, anaesthetists and observations. This programme was applied on a population of 65 women with ovarian malignancies. Subsequently analyses were performed...

  7. Oral contraceptive use and impact of cumulative intake of estrogen and progestin on risk of ovarian cancer

    DEFF Research Database (Denmark)

    Faber, M T; Jensen, A; Frederiksen, K;

    2013-01-01

    Oral contraceptive use decreases the risk of ovarian cancer, but no previous studies have assessed the impact of cumulative intake of estrogen and progestin on ovarian cancer risk.......Oral contraceptive use decreases the risk of ovarian cancer, but no previous studies have assessed the impact of cumulative intake of estrogen and progestin on ovarian cancer risk....

  8. [Erythropoietin and drug resistance in breast and ovarian cancers].

    Science.gov (United States)

    Szenajch, Jolanta M; Synowiec, Agnieszka E

    2016-01-01

    Recombinant human erythropoietin (rhEPO) is used in breast and ovarian cancer patients to alleviate cancer- and chemotherapy-related anemia. Some clinical trials have reported that rhEPO may adversely impact survival and increase the risk of thrombovascular events in patients with breast cancer but not with ovarian cancer. The latter may potentially benefit the most from rhEPO treatment due to the nephrotoxic and myelosuppresive effects of standard platinum-based chemotherapy used in ovarian cancer disease. However, over the last decade the preclinical data have revealed that EPO is not only the principal growth factor and the hormone which regulates erythropoiesis, but also a cytokine with a pleiotropic activity which also can affect cancer cells. EPO can stimulate survival, ability to form metastases and drug resistance not only in continuous breast- and ovarian cancer cell lines but also in breast cancer stem-like cells. EPO receptor (EPOR) can also be constitutively active in both these cancers and, in breast cancer cells, may act in an interaction with estrogen receptor (ER) and epidermal growth factor receptor-2 (HER-2). EPOR, by an EPO-independent mechanism, promotes proliferation of breast cancer cells in cooperation with estrogen receptor, resulting in decreased effectiveness of tamoxifen treatment. In another interaction, as a result of the molecular antagonism between EPOR and HER2, rhEPO protects breast cancer cells against trastuzumab. Both clinical and preclinical evidence strongly suggest the urgent need to reevaluate the traditional use of rhEPO in the oncology setting. PMID:27321103

  9. Thrombosis in ovarian cancer: a case control study

    OpenAIRE

    Metcalf, R L; Fry, D J; Swindell, R.; McGurk, A; Clamp, A R; Jayson, G C; Hasan, J

    2014-01-01

    Background: Thrombotic events are common in cancer patients and have been associated with an adverse prognosis in large registry-based studies. Methods: A retrospective cohort of 417 patients with ovarian cancer treated at a tertiary cancer centre between 2006 and 2009 was studied to identify the incidence and risk factors for thrombotic events and the prognostic impact of thrombosis. Patient outcomes were evaluated against a matched control group without thrombosis. Results: Ninety-nine thro...

  10. Loss-of-heterozygosity on chromosome 19q in early-stage serous ovarian cancer is associated with recurrent disease

    Directory of Open Access Journals (Sweden)

    Skirnisdottir Ingiridur

    2012-09-01

    Full Text Available Abstract Background Ovarian cancer is a heterogeneous disease and prognosis for apparently similar cases of ovarian cancer varies. Recurrence of the disease in early stage (FIGO-stages I-II serous ovarian cancer results in survival that is comparable to those with recurrent advanced-stage disease. The aim of this study was to investigate if there are specific genomic aberrations that may explain recurrence and clinical outcome. Methods Fifty-one women with early stage serous ovarian cancer were included in the study. DNA was extracted from formalin fixed samples containing tumor cells from ovarian tumors. Tumor samples from thirty-seven patients were analysed for allele-specific copy numbers using OncoScan single nucleotide polymorphism arrays from Affymetrix and the bioinformatic tool Tumor Aberration Prediction Suite. Genomic gains, losses, and loss-of-heterozygosity that associated with recurrent disease were identified. Results The most significant differences (p  Conclusions The results of our study indicate that presence of two aberrations in TP53 on 17p and LOH on 19q in early stage serous ovarian cancer is associated with recurrent disease. Further studies related to the findings of chromosomes 17 and 19 are needed to elucidate the molecular mechanism behind the recurring genomic aberrations and the poor clinical outcome.

  11. Ovarian hemangioma with elevated CA125 and ascites mimicking ovarian cancer.

    Science.gov (United States)

    Erdemoglu, E; Kamaci, M; Ozen, S; Sahin, H G; Kolusari, A

    2006-01-01

    We report a case of a very rare tumor of the ovary with an unusual presentation; an ovarian hemangioma with massive ascites and elevated CA125. A 57-year-old woman presenting with elevated CA125, massive ascites and a left solid adnexal mass of 60 x 47 mm, with calcification and increased blood flow at Doppler examination, was submitted to laparotomy. Frozen section was inconclusive and a staging procedure which complicated the patient was performed. Pathologic examination revealed cavernous hemangioma which is an extremely rare tumor of the ovary. Although it is very unusual, an ovarian hemangioma may present with ascites and elevated CA125 and the differential diagnosis from ovarian cancer should be considered. PMID:16620071

  12. 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.

  13. Ovarian Cancer Susceptibility Alleles and Risk of Ovarian Cancer in BRCA1 and BRCA2 Mutation Carriers

    Science.gov (United States)

    Ramus, Susan J.; Antoniou, Antonis C; Kuchenbaecker, Karoline B.; Soucy, Penny; Beesley, Jonathan; Chen, Xiaoqing; McGuffog, Lesley; Sinilnikova, Olga M.; Healey, Sue; Barrowdale, Daniel; Lee, Andrew; Thomassen, Mads; Gerdes, Anne-Marie; Kruse, Torben A.; Jensen, Uffe Birk; Skytte, Anne-Bine; Caligo, Maria A.; Liljegren, Annelie; Lindblom, Annika; Olsson, Håkan; Kristoffersson, Ulf; Stenmark-Askmalm, Marie; Melin, Beatrice; Domchek, Susan M.; Nathanson, Katherine L.; Rebbeck, Timothy R.; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Złowocka, Elżbieta; Gronwald, Jacek; Huzarski, Tomasz; Byrski, Tomasz; Cybulski, Cezary; Toloczko-Grabarek, Aleksandra; Osorio, Ana; Benitez, Javier; Duran, Mercedes; Tejada, Maria-Isabel; Hamann, Ute; Rookus, Matti; van Leeuwen, Flora E.; Aalfs, Cora M.; Meijers-Heijboer, Hanne E.J.; van Asperen, Christi J.; van Roozendaal, K.E.P.; Hoogerbrugge, Nicoline; Collée, J. Margriet; Kriege, Mieke; van der Luijt, Rob B.; Peock, Susan; Frost, Debra; Ellis, Steve D.; Platte, Radka; Fineberg, Elena; Evans, D. Gareth; Lalloo, Fiona; Jacobs, Chris; Eeles, Ros; Adlard, Julian; Davidson, Rosemarie; Eccles, Diana; Cole, Trevor; Cook, Jackie; Paterson, Joan; Douglas, Fiona; Brewer, Carole; Hodgson, Shirley; Morrison, Patrick J.; Walker, Lisa; Porteous, Mary E.; Kennedy, M. John; Pathak, Harsh; Godwin, Andrew K.; Stoppa-Lyonnet, Dominique; Caux-Moncoutier, Virginie; de Pauw, Antoine; Gauthier-Villars, Marion; Mazoyer, Sylvie; Léoné, Mélanie; Calender, Alain; Lasset, Christine; Bonadona, Valérie; Hardouin, Agnès; Berthet, Pascaline; Bignon, Yves-Jean; Uhrhammer, Nancy; Faivre, Laurence; Loustalot, Catherine; Buys, Saundra; Daly, Mary; Miron, Alex; Terry, Mary Beth; Chung, Wendy K.; John, Esther M; Southey, Melissa; Goldgar, David; Singer, Christian F; Tea, Muy-Kheng; Pfeiler, Georg; Fink-Retter, Anneliese; Hansen, Thomas v. O.; Ejlertsen, Bent; Johannsson, Oskar Th.; Offit, Kenneth; Kirchhoff, Tomas; Gaudet, Mia M.; Vijai, Joseph; Robson, Mark; Piedmonte, Marion; Phillips, Kelly-Anne; Van Le, Linda; Hoffman, James S; Toland, Amanda Ewart; Montagna, Marco; Tognazzo, Silvia; Imyanitov, Evgeny; Isaacs, Claudine; Janavicius, Ramunas; Lazaro, Conxi; Blanco, Ignacio; Tornero, Eva; Navarro, Matilde; Moysich, Kirsten B.; Karlan, Beth Y.; Gross, Jenny; Olah, Edith; Vaszko, Tibor; Teo, Soo-Hwang; Ganz, Patricia A.; Beattie, Mary S.; Dorfling, Cecelia M; van Rensburg, Elizabeth J; Diez, Orland; Kwong, Ava; Schmutzler, Rita K.; Wappenschmidt, Barbara; Engel, Christoph; Meindl, Alfons; Ditsch, Nina; Arnold, Norbert; Heidemann, Simone; Niederacher, Dieter; Preisler-Adams, Sabine; Gadzicki, Dorotehea; Varon-Mateeva, Raymonda; Deissler, Helmut; Gehrig, Andrea; Sutter, Christian; Kast, Karin; Fiebig, Britta; Schäfer, Dieter; Caldes, Trinidad; de la Hoya, Miguel; Nevanlinna, Heli; Aittomäki, Kristiina; Plante, Marie; Spurdle, Amanda B.; Neuhausen, Susan L.; Ding, Yuan Chun; Wang, Xianshu; Lindor, Noralane; Fredericksen, Zachary; Pankratz, V. Shane; Peterlongo, Paolo; Manoukian, Siranoush; Peissel, Bernard; Zaffaroni, Daniela; Bonanni, Bernardo; Bernard, Loris; Dolcetti, Riccardo; Papi, Laura; Ottini, Laura; Radice, Paolo; Greene, Mark H.; Mai, Phuong L.; Andrulis, Irene L.; Glendon, Gord; Ozcelik, Hilmi; Pharoah, Paul D.P.; Gayther, Simon A.; Simard, Jacques; Easton, Douglas F.; Couch, Fergus J.; Chenevix-Trench, Georgia

    2012-01-01

    Germline mutations in BRCA1 and BRCA2 are associated with increased risks of breast and ovarian cancer. A genome-wide association study (GWAS) identified six alleles associated with risk of ovarian cancer for women in the general population. We evaluated four of these loci as potential modifiers of ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Four single-nucleotide polymorphisms (SNPs), rs10088218 (at 8q24), rs2665390 (at 3q25), rs717852 (at 2q31), and rs9303542 (at 17q21), were genotyped in 12,599 BRCA1 and 7,132 BRCA2 carriers, including 2,678 ovarian cancer cases. Associations were evaluated within a retrospective cohort approach. All four loci were associated with ovarian cancer risk in BRCA2 carriers; rs10088218 per-allele hazard ratio (HR) = 0.81 (95% CI: 0.67–0.98) P-trend = 0.033, rs2665390 HR = 1.48 (95% CI: 1.21–1.83) P-trend = 1.8 × 10−4, rs717852 HR = 1.25 (95% CI: 1.10–1.42) P-trend = 6.6 × 10−4, rs9303542 HR = 1.16 (95% CI: 1.02–1.33) P-trend = 0.026. Two loci were associated with ovarian cancer risk in BRCA1 carriers; rs10088218 per-allele HR = 0.89 (95% CI: 0.81–0.99) P-trend = 0.029, rs2665390 HR = 1.25 (95% CI: 1.10–1.42) P-trend = 6.1 × 10−4. The HR estimates for the remaining loci were consistent with odds ratio estimates for the general population. The identification of multiple loci modifying ovarian cancer risk may be useful for counseling women with BRCA1 and BRCA2 mutations regarding their risk of ovarian cancer. PMID:22253144

  14. Predicting Ovarian Cancer Patients' Clinical Response to Platinum-Based Chemotherapy by Their Tumor Proteomic Signatures.

    Science.gov (United States)

    Yu, Kun-Hsing; Levine, Douglas A; Zhang, Hui; Chan, Daniel W; Zhang, Zhen; Snyder, Michael

    2016-08-01

    Ovarian cancer is the deadliest gynecologic malignancy in the United States with most patients diagnosed in the advanced stage of the disease. Platinum-based antineoplastic therapeutics is indispensable to treating advanced ovarian serous carcinoma. However, patients have heterogeneous responses to platinum drugs, and it is difficult to predict these interindividual differences before administering medication. In this study, we investigated the tumor proteomic profiles and clinical characteristics of 130 ovarian serous carcinoma patients analyzed by the Clinical Proteomic Tumor Analysis Consortium (CPTAC), predicted the platinum drug response using supervised machine learning methods, and evaluated our prediction models through leave-one-out cross-validation. Our data-driven feature selection approach indicated that tumor proteomics profiles contain information for predicting binarized platinum response (P drug responses as well as provided insights into the biological processes influencing the efficacy of platinum-based therapeutics. Our analytical approach is also extensible to predicting response to other antineoplastic agents or treatment modalities for both ovarian and other cancers. PMID:27312948

  15. Progesterone receptor variation and risk of ovarian cancer is limited to the invasive endometrioid subtype: results from the Ovarian Cancer Association Consortium pooled analysis

    DEFF Research Database (Denmark)

    Pearce, C.L.; Wu, A.H.; Gayther, S.A.;

    2008-01-01

    single nucleotide polymorphisms (SNPs), for which previous data have suggested they affect ovarian cancer risk, were examined. These were +331 C/T (rs10895068), PROGINS (rs1042838), and a 3' variant (rs608995). A total of 4788 ovarian cancer cases and 7614 controls from 12 case-control studies were...... analyses, we found a statistically significant association between risk of endometrioid ovarian cancer and the PROGINS allele (n=651, OR=1.17, 95% CI=1.01-1.36, P=0.036). We also observed borderline evidence of an association between risk of endometrioid ovarian cancer and the +331C/T variant (n=725 cases...

  16. Radiological diagnostics of ovarian cancer; Radiologische Diagnostik des Ovarialkarzinoms

    Energy Technology Data Exchange (ETDEWEB)

    Meissnitzer, M.; Forstner, R. [Paracelsus Medizinische Universitaet, Universitaetsinstitut fuer Radiologie, Salzburg (Austria)

    2011-07-15

    Ovarian cancer is diagnosed in stages FIGO III/IV in up to 75% of cases. Despite medical advances the 5-year survival rate has only been moderately increased to 44% during recent years. The initial evaluation is performed using transvaginal ultrasound (US) (sensitivity 90-96%, specificity 98-99% for detection of ovarian lesions). Probably benign findings will be followed-up sonographically or will be laparoscopically excised. Magnetic resonance imaging (MRI) allows a definitive diagnosis in more than 90% of sonographically indeterminate lesions. Malignant lesions require computer tomography (CT) staging and treatment in gynecooncology centers in a multidisciplinary setting. Peritoneal implants larger than 1 cm are detected equally by CT and MRI. Detection of ascites which is associated with peritoneal carcinomatosis in up to 80% of cases is equally feasible by US, CT and MRI. (orig.) [German] Die Diagnose ''Ovarialkarzinom'' wird in 75% der Faelle erst im Stadium FIGO III/IV gestellt, und die 5-Jahres-Ueberlebensrate konnte trotz medizinischer Fortschritte nur maessig auf 44% verbessert werden. Die Bildgebung erfolgt initial mittels transvaginalem Ultraschall (Sensitivitaet 90-96%, Spezifitaet 98-99% fuer ovarielle Laesionen). Benigne Befunde werden sonographisch im Verlauf kontrolliert oder laparoskopisch entfernt. Bei sonographisch unklaren Laesionen erlaubt die MRT in mehr als 90% eine definitive Diagnose. Sonographisch malignomsuspekte Laesionen sollten einem CT-Staging unterzogen werden. Diese Information ist entscheidend fuer die Therapiestratifizierung, die idealerweise in gynaekoonkologischen Zentren in multidisziplinaerer Zusammenarbeit erfolgt. Bei peritonealer Karzinose werden Implantationen ueber 1 cm in der CT und MRT vergleichbar gut detektiert. Ein Aszites, der beim Ovarialkarzinom in bis zu 80% der Faelle mit einer peritonealen Karzinose assoziiert ist, laesst sich gleichermassen mit Ultraschall, CT und MRT nachweisen. (orig.)

  17. 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.

  18. 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....

  19. Activation of hedgehog signaling is not a frequent event in ovarian cancers

    OpenAIRE

    Zhang Xiaoli; Huang Shuhong; He Jing; Yang Ling; Bian Yuehong; He Nonggao; Zhang Hongwei; Xie Jingwu

    2009-01-01

    Abstract The hedgehog (Hh) signaling pathway regulates many processes of development and tissue homeostasis. Activation of hedgehog signaling has been reported in about 30% of human cancer including ovarian cancer. Inhibition of hedgehog signaling has been pursued as an effective strategy for cancer treatment including an ongoing phase II clinical trial in ovarian cancer. However, the rate of hedgehog signaling activation in ovarian cancer was reported differently by different groups. To pred...

  20. DDX4 (DEAD box polypeptide 4) colocalizes with cancer stem cell marker CD133 in ovarian cancers

    International Nuclear Information System (INIS)

    Highlights: • Germ cell marker DDX4 was significantly increased in ovarian cancer. • Ovarian cancer stem cell marker CD133 was significantly increased in ovarian cancer. • DDX4 and CD133 were mostly colocalized in various types of ovarian cancer tissues. • CD133 positive ovarian cancer cells also express DDX4 whereas CD133-negative cells did not possess DDX4. • Germ cell marker DDX4 has the potential of ovarian cancer stem cell marker. - Abstract: DDX4 (DEAD box polypeptide 4), characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), is an RNA helicase which is implicated in various cellular processes involving the alteration of RNA secondary structure, such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. DDX4 is known to be a germ cell-specific protein and is used as a sorting marker of germline stem cells for the production of oocytes. A recent report about DDX4 in ovarian cancer showed that DDX4 is overexpressed in epithelial ovarian cancer and disrupts a DNA damage-induced G2 checkpoint. We investigated the relationship between DDX4 and ovarian cancer stem cells by analyzing the expression patterns of DDX4 and the cancer stem cell marker CD133 in ovarian cancers via tissue microarray. Both DDX4 and CD133 were significantly increased in ovarian cancer compared to benign tumors, and showed similar patterns of expression. In addition, DDX4 and CD133 were mostly colocalized in various types of ovarian cancer tissues. Furthermore, almost all CD133 positive ovarian cancer cells also express DDX4 whereas CD133-negative cells did not possess DDX4, suggesting a strong possibility that DDX4 plays an important role in cancer stem cells, and/or can be used as an ovarian cancer stem cell marker

  1. DDX4 (DEAD box polypeptide 4) colocalizes with cancer stem cell marker CD133 in ovarian cancers

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ki Hyung [Department of Obstetrics and Gynecology, Pusan National University School of Medicine, Busan (Korea, Republic of); Biomedical Research Institute and Pusan Cancer Center, Pusan National University Hospital, Busan (Korea, Republic of); Kang, Yun-Jeong; Jo, Jin-Ok; Ock, Mee Sun [Department of Parasitology and Genetics, Kosin University College of Medicine, Busan (Korea, Republic of); Moon, Soo Hyun; Suh, Dong Soo; Yoon, Man Soo [Department of Obstetrics and Gynecology, Pusan National University School of Medicine, Busan (Korea, Republic of); Biomedical Research Institute and Pusan Cancer Center, Pusan National University Hospital, Busan (Korea, Republic of); Park, Eun-Sil [Vincent Center for Reproductive Biology, Massachusetts General Hospital, Harvard Medical School, MA (United States); Jeong, Namkung [Department of Obstetrics and Gynecology, The Catholic University, Seoul (Korea, Republic of); Eo, Wan-Kyu [Department of Internal Medicine, Kyung Hee University, Seoul (Korea, Republic of); Kim, Heung Yeol, E-mail: hykyale@yahoo.com [Department of Obstetrics and Gynecology, Kosin University College of Medicine, Busan (Korea, Republic of); Cha, Hee-Jae, E-mail: hcha@kosin.ac.kr [Department of Parasitology and Genetics, Kosin University College of Medicine, Busan (Korea, Republic of); Institute for Medical Science, Kosin University College of Medicine, Busan (Korea, Republic of)

    2014-05-02

    Highlights: • Germ cell marker DDX4 was significantly increased in ovarian cancer. • Ovarian cancer stem cell marker CD133 was significantly increased in ovarian cancer. • DDX4 and CD133 were mostly colocalized in various types of ovarian cancer tissues. • CD133 positive ovarian cancer cells also express DDX4 whereas CD133-negative cells did not possess DDX4. • Germ cell marker DDX4 has the potential of ovarian cancer stem cell marker. - Abstract: DDX4 (DEAD box polypeptide 4), characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), is an RNA helicase which is implicated in various cellular processes involving the alteration of RNA secondary structure, such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. DDX4 is known to be a germ cell-specific protein and is used as a sorting marker of germline stem cells for the production of oocytes. A recent report about DDX4 in ovarian cancer showed that DDX4 is overexpressed in epithelial ovarian cancer and disrupts a DNA damage-induced G2 checkpoint. We investigated the relationship between DDX4 and ovarian cancer stem cells by analyzing the expression patterns of DDX4 and the cancer stem cell marker CD133 in ovarian cancers via tissue microarray. Both DDX4 and CD133 were significantly increased in ovarian cancer compared to benign tumors, and showed similar patterns of expression. In addition, DDX4 and CD133 were mostly colocalized in various types of ovarian cancer tissues. Furthermore, almost all CD133 positive ovarian cancer cells also express DDX4 whereas CD133-negative cells did not possess DDX4, suggesting a strong possibility that DDX4 plays an important role in cancer stem cells, and/or can be used as an ovarian cancer stem cell marker.

  2. 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.

  3. 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

  4. Effects of ovarian cancer G protein coupled receptor 1 on the proliferation, migration, and adhesion of human ovarian cancer cells

    Institute of Scientific and Technical Information of China (English)

    REN Juan; ZHANG Long

    2011-01-01

    Background OGR1 was found as a G-protein coupled receptor (GPCR) and proton sensor. Our previous studies have found that OGR1 has inhibitory effect on the metastasis of prostate cancer. In order to investigate the roles of OGR1 gene in the biological activities of ovarian cancer, we studied the OGR1 effects on ovarian cancer cells, HEY cells.Methods OGR1 gene was transfected into HEY cell, in which endogenous expression is low. OGR1-overxepressed cells and vector-transfected cells were compared in different assays. Western blotting was employed to confirm the high expression level of OGR1. Cell proliferation was determined by MTT assay and cell doubling time assay. Cell migration assay (transwell assay) and cell adhesion assay were performed to determine the migration and adhesion potential of cells. Student's t test was employed for statistical analysis.Results Proliferation of OGR1-overexpressed cells was significantly reduced (P <0.01); cell migration was significantly inhibited in the OGR1-transfected cells (P <0.01); cell adhesion to extracellular matrix including fibronectin, vitronectin,collagen Ⅰ/Ⅳ was significantly increased (P <0.01).Conclusions OGR1 expression in human ovarian cancer cells significantly inhibited the cell proliferation and migration,but significantly enhanced cell adhesion to the extracellular matrix. It indicated that OGR1 may be a tumor suppressor gene for ovarian cancer.

  5. 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

  6. Prognostic factors in ovarian cancer : current evidence and future prospects

    NARCIS (Netherlands)

    Crijns, APG; Boezen, HM; Schouten, JP; Arts, HJG; Hofstra, RMW; Willemse, PHB; de Vries, EGE; van der Zee, AGJ

    2003-01-01

    In ovarian cancer, translational research on the prognostic impact of molecular biological factors has until now not led to clinical implementation of any of these factors. This is partly due to the often conflicting results of different prognostic factor studies on the same molecular biological fac

  7. MEIS and PBX homeobox proteins in ovarian cancer

    NARCIS (Netherlands)

    Crijns, A. P. G.; de Graeff, P.; Geerts, D.; ten Hoor, K. A.; Hollema, H.; van der Sluis, T.; Hofstra, R. M. W.; de Bock, G. H.; de Jong, S.; van der Zee, A. G. J.; de Vries, E. G. E.

    2007-01-01

    Three amino-acid loop extension (TALE) homeobox proteins MEIS and PBX are cofactors for HOX-class homeobox proteins, which control growth and differentiation during embryogenesis and homeostasis. We showed that MEIS and PBX expression are related to cisplatin resistance in ovarian cancer cell lines.

  8. BRCA1- and BRCA2-Associated Ovarian Cancer: different diseases?

    NARCIS (Netherlands)

    P.M.L.H. Vencken (Peggy)

    2014-01-01

    markdownabstract__Abstract__ Ovarian cancer will develop in approximately 1.4% of the Dutch women accounting for approximately 1250 new patients yearly in the Netherlands, which is comparable with the incidence in other Western world countries. The disease mainly develops in women of 40 years of ag

  9. Disrupting Ovarian Cancer Metastatic Colonization: Insights from Metastasis Suppressor Studies

    Directory of Open Access Journals (Sweden)

    Shaheena Khan

    2010-01-01

    Full Text Available Ovarian cancer affects approximately 25,000 women in the United States each year and remains one of the most lethal female malignancies. A standard approach to therapy is surgical cytoreduction, after which the remaining microscopic residual disease is treated with chemotherapy. The vast majority of patients have disease recurrence, underscoring the crucial need for approaches to control the regrowth, or colonization, of tissues after local treatment. Improved therapies require mechanistic information about the process of metastatic colonization, the final step in metastasis, in which cancer cells undergo progressive growth at secondary sites. Studies of metastasis suppressors are providing insights into events controlling metastatic colonization. This paper reviews our laboratory's approach to the identification, characterization, and functional testing of the JNKK1/MKK4 metastasis suppressor in ovarian cancer metastatic colonization. Specifically, we demonstrate that interaction of ovarian caner cells with the omental microenvironment activates JNKK1/MKK4 resulting in decreased proliferation without affecting apoptosis. The potential role of the omental microenvironment, specifically milky spot structures, is also described. It is our goal to provide this work as a usable paradigm that will enable others to study metastasis suppressors in clinical and experimental ovarian cancer metastases.

  10. Shared genetics underlying epidemiological association between endometriosis and ovarian cancer

    DEFF Research Database (Denmark)

    Lu, Yi; Cuellar-Partida, Gabriel; Painter, Jodie N;

    2015-01-01

    Epidemiological studies have demonstrated associations between endometriosis and certain histotypes of ovarian cancer, including clear cell, low-grade serous and endometrioid carcinomas. We aimed to determine whether the observed associations might be due to shared genetic aetiology. To address t...

  11. Feasibility of serodiagnosis of ovarian cancer by mass spectrometry

    DEFF Research Database (Denmark)

    West-Norager, M.; Bro, R.; Marini, F.;

    2009-01-01

    The emergence of new biological disease markers from mass spectrometric studies of serum proteomes has been quite limited. There are challenges regarding the analytical and statistical procedures, preanalytical variability, and study designs. In this serological study of ovarian cancer, we apply ...

  12. ESUR guidelines: ovarian cancer staging and follow-up

    Energy Technology Data Exchange (ETDEWEB)

    Forstner, Rosemarie [Paracelsus Medical University, Department of Radiology, Landeskliniken Salzburg, Salzburg (Austria); Sala, Evis [University of Cambridge, Cambridge University Hospitals, NHS Foundation Trust, Cambridge (United Kingdom); Kinkel, Karen [Geneva University Hospital, Clinique des Grangettes, Geneva (Switzerland); Spencer, John A. [St James' s University Hospital, Leeds (United Kingdom)

    2010-12-15

    To design clear guidelines for the staging and follow-up of patients with ovarian cancer, and to provide the radiologist with a framework for use in multidisciplinary conferences. Guidelines for ovarian cancer staging and follow-up were defined by the female imaging subcommittee of the ESUR (European Society of Urogenital Radiology) based on the expert consensus of imaging protocols of 12 leading institutions and a critical review of the literature. Computed tomography (CT) with coverage of the base of the lungs to the inguinal region is regarded as the imaging technique of choice for preoperative staging. Critical diagnostic criteria are presented and the basis for a structured report for preoperative staging is outlined. Following primary treatment for ovarian cancer, clinical assessment and CA-125 are routinely used to monitor patients. For suspected recurrence, CT remains the imaging modality of choice, with positron emission tomography (PET)/CT emerging as the optimal imaging technique for suspected recurrence, particularly in patients with negative CT or magnetic resonance imaging (MRI). CT is the imaging modality of choice for preoperative staging and detection of recurrence in patients with ovarian cancer. (orig.)

  13. Sex Steroid Hormone Receptor Expression Affects Ovarian Cancer Survival

    DEFF Research Database (Denmark)

    Jönsson, Jenny-Maria; Skovbjerg Arildsen, Nicolai; Malander, Susanne;

    2015-01-01

    BACKGROUND AND AIMS: Although most ovarian cancers express estrogen (ER), progesterone (PR), and androgen (AR) receptors, they are currently not applied in clinical decision making. We explored the prognostic impact of sex steroid hormone receptor protein and mRNA expression on survival...

  14. 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...

  15. Symptom Interpretation and Health Care Seeking in Ovarian Cancer

    DEFF Research Database (Denmark)

    Seibæk, L.; Petersen, L. K.; Blaakaer, J.;

    2011-01-01

    BACKGROUND: Ovarian cancer is the leading cause of death among women suffering from gynaecological malignancies in the Western world. Worldwide, approximately 200,000 women are diagnosed with the disease each year. This article deals with the health care seeking and symptom interpretation process...

  16. Drug combination may be highly effective in recurrent ovarian cancer

    Science.gov (United States)

    Significant improvement with the use of a combination drug therapy for recurrent ovarian cancer was reported at the annual meeting of the American Society of Clinical Oncology meeting in Chicago. The trial compared the activity of a combination of the dru

  17. Inhibitory effect of ginsenoside Rg3 on ovarian cancer metastasis

    Institute of Scientific and Technical Information of China (English)

    XU Tian-min; CUI Man-hua; XIN Ying; GU Li-ping; JIANG Xin; SU Man-man; WANG Ding-ding; WANG Wen-jia

    2008-01-01

    Background Ginsenosides are main components extracted from ginseng, and ginsenoside Rg3 is one of the most important parts. Ginsenoside Rg3 has been found to inhibit several kinds of tumor growth and metastasis. The present study was undertaken to investigate the effect of ginsenoside Rg3 on human ovarian cancer metastasis and the possible mechanism.Methods The experimental lung metastasis models of ovarian cancer SKOV-3 and the assay of tumor-induced angiogenesis were used to observe the inhibitory effects of Rg3 on tumor metastasis and angiogenesis. The effect of Rg3 on invasive ability of SKOV-3 cells in vitro was detected by Boyden chamber, and immunofluorescence staining was used to recognize the expression of matrix metalloproteinase 9 (MMP-9) in SKOV-3 cells.Results In the experimental lung metastasis models of ovarian cancer, the number of tumor colonies in the lung and vessels oriented toward the tumor mass in each ginsenoside Rg3 group, was lower than that of control group. The invasive ability and MMP-9 expression of SKOV-3 cells decreased significantly after treatment with ginsenoside Rg3.Conclusions Ginsenoside Rg3 can significantly inhibit the metastasis of ovarian cancer. The inhibitory effect is partially due to inhibition of tumor-induced angiogenesis and decrease of invasive ability and MMP-9 expression of SKOV-3 cells.

  18. First-line therapy in ovarian cancer trials.

    Science.gov (United States)

    Thigpen, Tate; duBois, Andreas; McAlpine, Jessica; DiSaia, Philip; Fujiwara, Keiichi; Hoskins, William; Kristensen, Gunnar; Mannel, Robert; Markman, Maurie; Pfisterer, Jacobus; Quinn, Michael; Reed, Nick; Swart, Ann Marie; Berek, Jonathan; Colombo, Nicoletta; Freyer, Gilles; Gallardo, Dolores; Plante, Marie; Poveda, Andres; Rubinstein, Lawrence; Bacon, Monica; Kitchener, Henry; Stuart, Gavin C E

    2011-05-01

    At the 4th Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup (GCIG) held in Vancouver, Canada, in June 2010, representatives of 23 cooperative research groups studying gynecologic cancers gathered to establish international consensus on issues critical to the conduct of large randomized trials. The process focused on 13 predetermined questions. Group A, 1 of the 3 discussion groups, addressed the first 5 questions, examining first-line therapies in newly diagnosed ovarian cancer patients. A1: What are the appropriate end points for different trials (maintenance, upfront chemotherapy trials including molecular drugs)? A2: Are there any subgroups defined by tumor biology who need specific treatment options/trials? A3: Is the 2004 GCIG-recommended standard comparator arm still valid? A4: What is the role of modifying dose, schedule, and delivery of chemotherapy? A5: What role does surgery play today?

  19. Molecular subtyping of serous ovarian tumors reveals multiple connections to intrinsic breast cancer subtypes.

    Directory of Open Access Journals (Sweden)

    Jenny-Maria Jönsson

    Full Text Available OBJECTIVE: Transcriptional profiling of epithelial ovarian cancer has revealed molecular subtypes correlating to biological and clinical features. We aimed to determine gene expression differences between malignant, benign and borderline serous ovarian tumors, and investigate similarities with the well-established intrinsic molecular subtypes of breast cancer. METHODS: Global gene expression profiling using Illumina's HT12 Bead Arrays was applied to 59 fresh-frozen serous ovarian malignant, benign and borderline tumors. Nearest centroid classification was performed applying previously published gene profiles for the ovarian and breast cancer subtypes. Correlations to gene expression modules representing key biological breast cancer features were also sought. Validation was performed using an independent, publicly available dataset. RESULTS: 5,944 genes were significantly differentially expressed between benign and malignant serous ovarian tumors, with cell cycle processes enriched in the malignant subgroup. Borderline tumors were split between the two clusters. Significant correlations between the malignant serous tumors and the highly aggressive ovarian cancer signatures, and the basal-like breast cancer subtype were found. The benign and borderline serous tumors together were significantly correlated to the normal-like breast cancer subtype and the ovarian cancer signature derived from borderline tumors. The borderline tumors in the study dataset, in addition, also correlated significantly to the luminal A breast cancer subtype. These findings remained when analyzed in an independent dataset, supporting links between the molecular subtypes of ovarian cancer and breast cancer beyond those recently acknowledged. CONCLUSIONS: These data link the transcriptional profiles of serous ovarian cancer to the intrinsic molecular subtypes of breast cancer, in line with the shared clinical and molecular features between high-grade serous ovarian cancer and

  20. 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

  1. 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

  2. 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.

  3. Identification of candidate methylation-responsive genes in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Dickerson Erin B

    2007-01-01

    Full Text Available Abstract Background Aberrant methylation of gene promoter regions has been linked to changes in gene expression in cancer development and progression. Genes associated with CpG islands (CGIs are especially prone to methylation, but not all CGI-associated genes display changes in methylation patterns in cancers. Results In order to identify genes subject to regulation by methylation, we conducted gene expression profile analyses of an ovarian cancer cell line (OVCAR-3 before and after treatment with the demethylating agent 5-aza-deoxycytidine (5-aza-dC. An overlapping subset of these genes was found to display significant differences in gene expression between normal ovarian surface epithelial cells and malignant cells isolated from ovarian carcinomas. While 40% of all human genes are associated with CGIs, > 94% of the overlapping subset of genes is associated with CGIs. The predicted change in methylation status of genes randomly selected from the overlapping subset was experimentally verified. Conclusion We conclude that correlating genes that are upregulated in response to 5-aza-dC treatment of cancer cell lines with genes that are down-regulated in cancer cells may be a useful method to identify genes experiencing epigenetic-mediated changes in expression over cancer development.

  4. Integrated Analysis of Germline and Somatic Variants in Ovarian Cancer

    OpenAIRE

    Kanchi, Krishna L.; Johnson, Kimberly J.; Lu, Charles; McLellan, Michael D; Mark D M Leiserson; Wendl, Michael C; Zhang, Qunyuan; Koboldt, Daniel C.; Xie, Mingchao; Kandoth, Cyriac; McMichael, Joshua F.; Wyczalkowski, Matthew A.; Larson, David E.; Schmidt, Heather K.; Christopher A Miller

    2014-01-01

    We report the first large-scale exome-wide analysis of the combined germline-somatic landscape in ovarian cancer. Here we analyze germline and somatic alterations in 429 ovarian carcinoma cases and 557 controls. We identify 3,635 high confidence, rare truncation and 22,953 missense variants with predicted functional impact. We find germline truncation variants and large deletions across Fanconi pathway genes in 20% of cases. Enrichment of rare truncations is shown in BRCA1, BRCA2, and PALB2. ...

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  6. 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...

  7. Genome-wide Analysis Identifies Novel Loci Associated with Ovarian Cancer Outcomes: Findings from the Ovarian Cancer Association Consortium

    NARCIS (Netherlands)

    Johnatty, S.E.; Tyrer, J.P.; Kar, S.; Beesley, J.; Lu, Y.; Gao, B.; Fasching, P.A.; Hein, A.; Ekici, A.B.; Beckmann, M.W.; Lambrechts, D.; Nieuwenhuysen, E. Van; Vergote, I.; Lambrechts, S.; Rossing, M.A.; Doherty, J.A.; Chang-Claude, J.; Modugno, F.; Ness, R.B.; Moysich, K.B.; Levine, D.A.; Kiemeney, L.A.L.M.; Massuger, L.F.A.G.; Gronwald, J.; Lubinski, J.; Jakubowska, A.; Cybulski, C.; Brinton, L.; Lissowska, J.; Wentzensen, N.; Song, H.; Rhenius, V.; Campbell, I.; Eccles, D.; Sieh, W.; Whittemore, A.S.; McGuire, V.; Rothstein, J.H.; Sutphen, R.; Anton-Culver, H.; Ziogas, A.; Gayther, S.A.; Gentry-Maharaj, A.; Menon, U.; Ramus, S.J.; Pearce, C.L.; Pike, M.C.; Stram, D.O.; Wu, A.H.; Kupryjanczyk, J.; Dansonka-Mieszkowska, A.; Rzepecka, I.K.; Spiewankiewicz, B.; Goodman, M.T.; Wilkens, L.R.; Carney, M.E.; Thompson, P.J.; Heitz, F.; Bois, A. du; Schwaab, I.; Harter, P.; Pisterer, J.; Hillemanns, P.; Karlan, B.Y.; Walsh, C.; Lester, J.; Orsulic, S.; Winham, S.J.; Earp, M.; Larson, M.C.; Fogarty, Z.C.; Hogdall, E.; Jensen, A.; Kjaer, S.K.; Fridley, B.L.; Cunningham, J.M.; Vierkant, R.A.; Schildkraut, J.M.; Iversen, E.S.; Terry, K.L.; Cramer, D.W; Bandera, E.V.; Orlow, I.; Pejovic, T.; Bean, Y.; Hogdall, C.; Lundvall, L.; McNeish, I.; Paul, J.; Carty, K.; Siddiqui, N.; Glasspool, R.; Sellers, T.; Kennedy, C.; Chiew, Y.E.; Berchuck, A.; MacGregor, S.; Pharoah, P.D.; Goode, E.L.; Defazio, A.

    2015-01-01

    PURPOSE: Chemotherapy resistance remains a major challenge in the treatment of ovarian cancer. We hypothesize that germline polymorphisms might be associated with clinical outcome. EXPERIMENTAL DESIGN: We analyzed approximately 2.8 million genotyped and imputed SNPs from the iCOGS experiment for pro

  8. 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

  9. Activated T-cell Therapy, Low-Dose Aldesleukin, and Sargramostim in Treating Patients With Ovarian, Fallopian Tube, or Primary Peritoneal Cancer That is Stage III-IV, Refractory, or Recurrent

    Science.gov (United States)

    2016-02-15

    Malignant Ovarian Clear Cell Tumor; Malignant Ovarian Serous Tumor; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; 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

  10. 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

  11. Venous thromboembolism in ovarian cancer: incidence, risk factors and impact on survival.

    LENUS (Irish Health Repository)

    Abu Saadeh, Feras

    2013-09-01

    Ovarian cancer has a higher incidence of venous thromboembolism (VTE) than other cancers. Clear cell cancers carry the highest risk at 11-27%. The aim of this study was to identify the predisposing factors for VTE in a population of ovarian cancer patients and to determine the influence of VTE on overall survival.

  12. Identification of high-risk patients by human epididymis protein 4 levels during follow-up of ovarian cancer

    DEFF Research Database (Denmark)

    Dahl Steffensen, Karina; Waldstrøm, Marianne; Brandslund, Ivan;

    2016-01-01

    The majority of ovarian cancer patients with advanced disease at diagnosis will relapse following primary treatment, with a dismal prognosis. Monitoring the levels of serum markers in patients under follow-up may be essential for the early detection of relapse, and for distinguishing high-risk pa...

  13. Impact of ABCB1 Variants on Neutrophil Depression: A Pharmacogenomic Study of Paclitaxel in 92 Women with Ovarian Cancer

    DEFF Research Database (Denmark)

    Bergmann, Troels K; Andersen, Charlotte Brasch; Gréen, Henrik;

    2012-01-01

      The standard treatment for ovarian cancer in advanced stages is post-surgery treatment with taxane-platin chemotherapy. Despite an initial high response rate, most patients eventually relapse. The dose-limiting toxicities of paclitaxel are neutropenia and neuropathy, but the inter-individual va...

  14. 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....

  15. Low 25-OH vitamin D levels at time of diagnosis and recurrence of ovarian cancer.

    Science.gov (United States)

    Granato, Teresa; Manganaro, Lucia; Petri, Luca; Porpora, Maria Grazia; Viggiani, Valentina; Angeloni, Antonio; Anastasi, Emanuela

    2016-02-01

    The objective of this study was to evaluate the correlation between 25-OH vitamin D and ovarian cancer as a diagnostic marker or recurrence disease marker. We studied the following: (1) 61 women without gynecologic diseases, (2) 45 women affected by benign ovarian disease, (3) 46 women with recent diagnosis of ovarian cancer, (4) 26 follow-up women with recurrent ovarian cancer, and (5) 32 follow-up women with stable ovarian cancer. The 25-OH vitamin D was quantified with LUMIPULSE® G 25-OH vitamin D on LUMIPULSE® G 1200 (Fujirebio, Japan). As a threshold value, identified by ROC curve analysis, 20.2 ng/mL (sensitivity 73.3 %, specificity 84 %) was chosen corresponding to the limit between sufficient and insufficient 25-OH vitamin D according to the WHO. Low 25-OH vitamin D levels were observed in 26 % of women without gynecologic diseases, in 80 % of women with recent diagnosis of ovarian cancer and in 24 % women affected by benign ovarian diseases (p < 0.001). The follow-up study showed an insufficient level of 25-OH vitamin D in 73 % women with recurrent ovarian cancer and in 47 % women with stable ovarian cancer (p < 0.0003). This study showed that patients with ovarian cancer are often insufficient in 25-OH vitamin D compared to women with benign ovarian diseases. The women with recurrent ovarian cancer presented more often low levels compared to women with stable ovarian cancer. This study suggests that 25-OH vitamin D, due to its antiproliferative properties, can be a good marker for ovarian cancer also.

  16. Research Progress of MicroRNA in Early Detection of Ovarian Cancer

    Institute of Scientific and Technical Information of China (English)

    Ze-Hua Wang; Cong-Jian Xu

    2015-01-01

    Objective: This review aimed to update the progress ofmicroRNA (miRNA) in early detection of ovarian cancer.We discussed the current clinical diagnosis methods and biomarkers of ovarian cancer, especially the methods of miRNA in early detection of ovarian cancer.Data Sources: We collected all relevant studies about miRNA and ovarian cancer in PubMed and CNKI from 1995 to 2015.Study Selection: We included all relevant studies concerning miRNA in early detection of ovarian cancer, and excluded the duplicated articles.Results: miRNAs play a key role in various biological processes of ovarian cancer, such as development, proliferation, differentiation, apoptosis and metastasis, and these phenomena appear in the early-stage.Therefore, miRNA can be used as a new biomarker for early diagnosis of ovarian cancer, intervention on miRNA expression of known target genes, and potential target genes can achieve the effect of early prevention.With the development ofnanoscience and technology, analysis methods ofmiRNA are also quickly developed, which may provide better characterization of early detection of ovarian cancer.Conclusions: In the near future, miRNA therapy could be a powerful tool for ovarian cancer prevention and treatment, and combining with the new analysis technology and new nanomaterials, point-of-care tests for miRNA with high throughput, high sensitivity, and strong specificity are developed to achieve the application of diagnostic kits in screening of early ovarian cancer.

  17. Trabectedin as a single agent and in combination with pegylated liposomal doxorubicin – activity against ovarian cancer cells

    OpenAIRE

    Marczak, Agnieszka; Denel, Marta

    2014-01-01

    Over 225 000 new cases of ovarian cancer are diagnosed each year. Symptoms are often vague, so most cases are detected when the disease is at an advanced stage. There is a need to find new drugs which will be able to treat ovarian cancer effectively. One of the most promising antineoplastic agents is trabectedin (Yondelis), derived from the marine tunicate Ecteinascidia turbinata, approved by the European Union in July 2007 for the treatment of soft-tissue sarcomas. This drug shows a mechanis...

  18. Unique proteome signature of post-chemotherapy ovarian cancer ascites-derived tumor cells.

    Science.gov (United States)

    Ahmed, Nuzhat; Greening, David; Samardzija, Chantel; Escalona, Ruth M; Chen, Maoshan; Findlay, Jock K; Kannourakis, George

    2016-01-01

    Eighty % of ovarian cancer patients diagnosed at an advanced-stage have complete remission after initial surgery and chemotherapy. However, most patients die within identification of 353 proteins. There were significant differences in proteins encoding for immune surveillance, DNA repair mechanisms, cytoskeleton rearrangement, cell-cell adhesion, cell cycle pathways, cellular transport, and proteins involved with glycine/proline/arginine synthesis in tumor cells isolated from CR relative to CN patients. Pathway analyses revealed enrichment of metabolic pathways, DNA repair mechanisms and energy metabolism pathways in CR tumor cells. In conclusion, this is the first proteomics study to comprehensively analyze ascites-derived tumor cells from CN and CR ovarian cancer patients. PMID:27470985

  19. Targeting TBP-associated factors in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Jennifer R Ribeiro

    2014-03-01

    Full Text Available As ovarian tumors progress, they undergo a process of dedifferentiation, allowing adaptive changes in growth and morphology that promote metastasis and chemoresistance. Herein, we outline a hypothesis that TATA-box binding protein (TBP associated factors (TAFs, which compose the RNA Polymerase II initiation factor, TFIID, contribute to regulation of dedifferentiation states in ovarian cancer. Numerous studies demonstrate that TAFs regulate differentiation and proliferation states; their expression is typically high in pluripotent cells and reduced upon differentiation. Strikingly, TAF2 exhibits copy number increases or mRNA overexpression in 73% of high grade serous ovarian cancers (HGSC. At the biochemical level, TAF2 directs TFIID to TATA-less promoters by contact with an Initiator element, which may lead to the deregulation of the transcriptional output of these tumor cells. TAF4, which is altered in 66% of HGSC, is crucial for the stability of the TFIID complex and helps drive dedifferentiation of mouse embryonic fibroblasts to induced pluripotent stem cells. Its ovary-enriched paralog, TAF4B, is altered in 26% of HGSC. Here, we show that Taf4b mRNA correlates with Cyclin D2 mRNA expression in human granulosa cell tumors. TAF4B may also contribute to regulation of tumor microenvironment due to its estrogen-responsiveness and ability to act as a cofactor for NFκB. Conversely, TAF9, a cofactor for p53 in regulating apoptosis, may act as a tumor suppressor in ovarian cancer, since it is downregulated or deleted in 98% of HGSC. We conclude that a greater understanding of mechanisms of transcriptional regulation that execute signals from oncogenic signaling cascades is needed in order to expand our understanding of the etiology and progression of ovarian cancer, and most importantly to identify novel targets for therapeutic intervention.

  20. Validation of Candidate Serum Ovarian Cancer Biomarkers for Early Detection

    Directory of Open Access Journals (Sweden)

    Feng Su

    2007-01-01

    Full Text Available Objective: We have previously analyzed protein profi les using Surface Enhanced Laser Desorption and Ionization Time-Of-Flight Mass Spectroscopy (SELDI-TOF-MS [Kozak et al. 2003, Proc. Natl. Acad. Sci. U.S.A. 100:12343–8] and identified 3 differentially expressed serum proteins for the diagnosis of ovarian cancer (OC [Kozak et al. 2005, Proteomics, 5:4589–96], namely, apolipoprotein A-I (apoA-I, transthyretin (TTR and transferin (TF. The objective of the present study is to determine the efficacy of the three OC biomarkers for the detection of early stage (ES OC, in direct comparison to CA125.Methods: The levels of CA125, apoA-I, TTR and TF were measured in 392 serum samples [82 women with normal ovaries (N, 24 women with benign ovarian tumors (B, 85 women with ovarian tumors of low malignant potential (LMP, 126 women with early stage ovarian cancer (ESOC, and 75 women with late stage ovarian cancer (LSOC], obtained through the GOG and Cooperative Human Tissue Network. Following statistical analysis, multivariate regression models were built to evaluate the utility of the three OC markers in early detection.Results: Multiple logistic regression models (MLRM utilizing all biomarker values (CA125, TTR, TF and apoA-I from all histological subtypes (serous, mucinous, and endometrioid adenocarcinoma distinguished normal samples from LMP with 91% sensitivity (specifi city 92%, and normal samples from ESOC with a sensitivity of 89% (specifi city 92%. MLRM, utilizing values of all four markers from only the mucinous histological subtype showed that collectively, CA125, TTR, TF and apoA-I, were able to distinguish normal samples from mucinous LMP with 90% sensitivity, and further distinguished normal samples from early stage mucinous ovarian cancer with a sensitivity of 95%. In contrast, in serum samples from patients with mucinous tumors, CA125 alone was able to distinguish normal samples from LMP and early stage ovarian cancer with a sensitivity of

  1. 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.

  2. Contrary to Evidence, Some Doctors Recommend Ovarian Cancer Screening | Division of Cancer Prevention

    Science.gov (United States)

    One in three doctors believes that screening for ovarian cancer is effective, according to a recently published survey of practicing physicians, even though substantial evidence to the contrary exists. |

  3. Coregistered photoacoustic and ultrasound imaging and classification of ovarian cancer: ex vivo and in vivo studies

    Science.gov (United States)

    Salehi, Hassan S.; Li, Hai; Merkulov, Alex; Kumavor, Patrick D.; Vavadi, Hamed; Sanders, Melinda; Kueck, Angela; Brewer, Molly A.; Zhu, Quing

    2016-04-01

    Most ovarian cancers are diagnosed at advanced stages due to the lack of efficacious screening techniques. Photoacoustic tomography (PAT) has a potential to image tumor angiogenesis and detect early neovascular changes of the ovary. We have developed a coregistered PAT and ultrasound (US) prototype system for real-time assessment of ovarian masses. Features extracted from PAT and US angular beams, envelopes, and images were input to a logistic classifier and a support vector machine (SVM) classifier to diagnose ovaries as benign or malignant. A total of 25 excised ovaries of 15 patients were studied and the logistic and SVM classifiers achieved sensitivities of 70.4 and 87.7%, and specificities of 95.6 and 97.9%, respectively. Furthermore, the ovaries of two patients were noninvasively imaged using the PAT/US system before surgical excision. By using five significant features and the logistic classifier, 12 out of 14 images (86% sensitivity) from a malignant ovarian mass and all 17 images (100% specificity) from a benign mass were accurately classified; the SVM correctly classified 10 out of 14 malignant images (71% sensitivity) and all 17 benign images (100% specificity). These initial results demonstrate the clinical potential of the PAT/US technique for ovarian cancer diagnosis.

  4. Risk perception and cancer worries in families at increased risk of familial breast/ovarian cancer

    OpenAIRE

    Mellon, Suzanne; Gold, Robin; Janisse, James; Cichon, Michelle; Tainsky, Michael A; Simon, Michael S.; Korczak, Jeannette

    2008-01-01

    While families at increased risk for familial breast/ovarian cancer continue to overestimate their cancer risk with increased cancer worries about the future, few studies have examined factors that affect inherited cancer risk perception and cancer worries in both survivors and unaffected female relatives. The purpose of this study was to examine variables that may affect cancer worries and risk perceptions from a family-based perspective in a racially diverse, community-based, random sample ...

  5. Consortium analysis of 7 candidate SNPs for ovarian cancer

    DEFF Research Database (Denmark)

    Ramus, S.J.; Vierkant, R.A.; Johnatty, S.E.;

    2008-01-01

    The Ovarian Cancer Association Consortium selected 7 candidate single nucleotide polymorphisms (SNPs), for which there is evidence from previous studies of an association with variation in ovarian cancer or breast cancer risks. The SNPs selected for analysis were F31I (rs2273535) in AURKA, N372H...... was suggestive although no longer statistically significant (ordinal OR 0.92, 95% CI 0.79-1.06). This SNP has also been shown to have an association with decreased risk in breast cancer. There was a suggestion of an association for AURKA, when one study that caused significant study heterogeneity was excluded...... [ordinal OR 1.10 (95% CI 1.01-1.20) p = 0.027; dominant OR 1.12 (95% CI 1.01-1.24) p = 0.03]. The other 5 SNPs in BRCA2, CDKN2A, SRD5A2, CASP8 and TGFB1 showed no association with ovarian cancer risk; given the large sample size, these results can also be considered to be informative. These null results...

  6. Cancer incidence in the first-degree relatives of ovarian cancer patients.

    OpenAIRE

    Auranen, A; Pukkala, E.; Mäkinen, J.; Sankila, R.; Grénman, S.; Salmi, T.

    1996-01-01

    Cancer incidence was studied among 3072 first-degree relatives of 559 unselected ovarian cancer patients. Among cohort members there were 306 cancer cases. The overall cancer incidence was not increased: the standardised incidence ratio (SIR) in males was 0.9 (95% confidence interval 0.8-1.1) and in females 1.0 (0.8-1.1). The female relatives had a significantly increased risk for ovarian cancer (SIR 2.8, 1.8-4.2). The excess was attributable to sisters only (SIR 3.7, 2.3-5.7). The relative r...

  7. TRPM7 is required for ovarian cancer cell growth, migration and invasion

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jing; Liao, Qian-jin [The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013 (China); Zhang, Yi [Department of Obstetrics and Gynaecology, Xiangya Hospital, Central South University, Changsha 410078 (China); Zhou, Hui; Luo, Chen-hui; Tang, Jie; Wang, Ying; Tang, Yan; Zhao, Min; Zhao, Xue-heng [The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013 (China); Zhang, Qiong-yu [Department of Basic Medical Science, Yongzhou Vocational Technical College, Yong Zhou 425100 (China); Xiao, Ling, E-mail: lingxiaocsu@126.com [Department of Histology and Embryology, School of Basic Medical Sciences, Central South University, Changsha 410013 (China); Institute of Clinical Pharmacology, Central South University, Changsha 410018 (China)

    2014-11-28

    Highlights: • Silence of TRPM7 in ovarian cancer cells inhibits cell proliferation, migration and invasion. • Silence of TRPM7 decreases phosphorylation levels of Akt, Src and p38 in ovarian cancer cells. • Silence of TRPM7 increases expression of filamentous actin and number of focal adhesions in ovarian cancer cells. - Abstract: Our previous study demonstrated that the melastatin-related transient receptor potential channel 7 (TRPM7) was highly expressed in ovarian carcinomas and its overexpression was significantly associated with poor prognosis in ovarian cancer patients. However, the function of TRPM7 in ovarian cancer is mostly unknown. In this study, we examined the roles of TRPM7 in ovarian cancer cell proliferation, migration and invasion. We found that short hairpin RNA interference-mediated silence of TRPM7 significantly inhibited cell proliferation, colony formation, migration and invasion in multiple ovarian cancer cell lines. Mechanistic investigation revealed that silence of TRPM7 decreased phosphorylation levels of Akt, Src and p38 and increased filamentous actin and focal adhesion number in ovarian cancer cells. Thus, our results suggest that TRPM7 is required for proliferation, migration and invasion of ovarian cancer cells through regulating multiple signaling transduction pathways and the formation of focal adhesions.

  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. Genetic Variants in Matrix Metalloproteinase Genes as Disposition Factors for Ovarian Cancer Risk, Survival, and Clinical Outcome

    OpenAIRE

    Yan WANG; Ye, Yuanqing; Lin, Jie; Meyer, Larissa; Wu, Xifeng; Lu, Karen; Liang, Dong

    2013-01-01

    Ovarian cancer is one of the leading female cancers in the United States. Challenges remain in early diagnosis of this deadly disease. Matrix metalloproteinases (MMPs) family genes are paradoxically involved in cancer promotion and suppression. We hypothesize that genetic variants in MMP genes are associated with ovarian cancer development, so they could be potential markers for ovarian cancer diagnosis and prognosis. In this study of 417 ovarian cancer cases and 417 healthy controls, we geno...

  10. Does ovarian stimulation for IVF increase gynaecological cancer risk? A systematic review and meta-analysis.

    Science.gov (United States)

    Zhao, Jing; Li, Yanping; Zhang, Qiong; Wang, Yonggang

    2015-07-01

    The aim of this study was to evaluate whether ovarian stimulation for IVF increases the risk of gynaecological cancer, including ovarian, endometrial, cervical and breast cancers, as an independent risk factor. A systematic review and meta-analysis was conducted. Clinical trials that examined the association between ovarian stimulation for IVF and gynaecologic cancers were included. The outcomes of interest were incidence rate of gynaecologic cancers. Twelve cohort studies with 178,396 women exposed to IVF were included; 10 studies were used to analyse ovarian (167,640 women) and breast (151,702 women) cancers, and six studies were identified in the analysis of endometrial (116,672 women) and cervical cancer (114,799 women). Among these studies, 175 ovarian, 48 endometrial, 502 cervical and 866 cases of breast cancer were reported. The meta-analysis found no significant association between ovarian stimulation for IVF and increased ovarian, endometrial, cervical and breast cancer risk (odds ratio [OR] 1.06, 95% confidence interval [CI] 0.85 to 1.32; OR 0.97, 95% CI 0.58 to 1.63; OR 0.43, 95% CI 0.30 to 0.60; OR 0.69, 95% CI 0.63 to 0.76, respectively). Ovarian stimulation for IVF, therefore, does not increase the gynaecologic cancer risk, whether hormone-dependent endometrial and breast cancer or non-hormone-dependent ovarian and cervical cancer. PMID:26003452

  11. CHARACTERISTICS OF MORTALITY RATES FROM BREAST AND OVARIAN CANCER IN JAPAN

    Institute of Scientific and Technical Information of China (English)

    LI Xiang-ming李湘鸣; LUO Fang-ni罗方妮; Akio Sato

    2004-01-01

    Objective: Breast and ovarian cancer is rare in Japan compared with other developed countries but their mortality rates are increasing. It is necessary to examine the experience of Japan as a guide to further prevent breast and ovarian cancer in our country. Methods: We conducted an epidemiological study of breast and ovarian cancer in the past 50 years to investigate the trends and characteristics of the mortality rates in Japan. The numbers of age-specific death from breast and ovarian cancer and the population of 5-year groups were obtained from the Vital Statistics of Japan. The truncated age specific mortality rates were calculated according to the patterns of age specific mortality rates from both cancers. Age adjustments were made to the standard world population. Results: In the past 50 years, mortality rates of breast and ovarian cancer increased about 2 or 6 fold, respectively. This increase was most marked over 50 years old. The death pattern of breast cancer was same as that of ovarian cancer, but that of ovarian cancer changed greatly with time. The birth cohort study had some interesting findings. Common to breast and ovarian cancer, the later the year of birth, the higher the mortality rates from both malignancies in later life. Conclusion: The increase of the yearly mortality rates from breast and ovarian cancer might be due to changes in lifestyle and environmental factors. We are very concerned about dietary practices. Further investigation is needed to clarify the possible causes of animal food.

  12. Tumor infiltrating lymphocyte therapy for ovarian cancer and renal cell carcinoma

    DEFF Research Database (Denmark)

    Andersen, Rikke; Donia, Marco; Westergaard, Marie Christine Wulff;

    2015-01-01

    therapy in solid tumors other than melanoma have shown limited success, however none of these early trials used current preparative chemotherapy regimens, and the methods for in vitro lymphocyte expansion have changed considerably. New advances and understandings in T cell based immunotherapies have...... the major advances in the characterization and application of TIL therapy for patients with RCC and OC....... stimulated the interest in developing this approach for other indications. Here, we summarize the early clinical data in the field of adoptive cell transfer therapy (ACT) using tumor-infiltrating lymphocytes for patients with renal cell carcinoma (RCC) and ovarian cancer (OC). In addition we describe...

  13. Right Place, Right Time: Preferences of Women with Ovarian Cancer for Delivery of CAM Education

    Directory of Open Access Journals (Sweden)

    Judith Ann Ebbert

    2015-08-01

    Full Text Available The purpose of this pilot study was to assess the feasibility of on-site complementary and alternative medicine (CAM education sessions to maximize quality of life for women with ovarian cancer. The pilot intervention consisted of four weekly sessions, each focusing the techniques and benefits of a particular CAM topic (e.g., nutrition, massage, relaxation. Participants were recruited from the Center for Women’s Oncology at H. Lee Moffitt Cancer Center from 2010 to 2012. Eligible participants had an ovarian cancer diagnosis with a life expectancy of at least 12 months, and were 18 years or older. The Gynecologic Oncology research nurse invited women in the outpatient clinic who matched the eligibility criteria. The research nurse explained the study and provided an informed consent form and return envelope. Because ovarian cancer is not only a rare cancer but, also, most patients seen at Moffitt have recurrent or advanced disease, many women did not have an adequate ECOG score. Many women who consented had rapid changes in health status, with morbidity and mortality outpacing recruitment of the 20 needed to proceed with the four education sessions. Baseline and follow-up surveys were conducted to assess changes in QOL, knowledge, and satisfaction with the intervention. While 27 women consented and 24 women completed the baseline survey, only five women participated in the intervention. The five women who participated were all white, and at time of consenting had a mean age of 60 (SD 9.08 and an average of 102 months (SD 120.65 since diagnosis, and were all on active treatment, except for one. The intervention pilot did not encounter difficulties with regard to recruitment, but suffered problems in achieving an adequate number of women to launch the on-site sessions because of rapidly changing morbidity and significant mortality. The team recognized that a larger-scaled intervention comprised of on-site sessions was impractical and compared

  14. BREAST AND/OR OVARIAN CANCER AS PART OF FAMILY CANCER SYNDROME

    OpenAIRE

    L N Lyubchenko; N. I. Pospelova; A. A. Parokonnaya; A. A. Luzhnikova; E. M. Chevkina

    2014-01-01

    The problems in the early diagnosis, primary and secondary prevention of family cancer of the breast and/or ovaries are successfully solved within medical genetic counseling at a cancer clinic. Its genetic diagnosis is confirmed, individual risks for breast and/or ovarian cancer are calculated, risk-modifying factors are studied, and treatment, family planning, and childbirth are discussed during clinicogenetic studies.

  15. Current principles of effective therapy for ovarian cancer

    Directory of Open Access Journals (Sweden)

    L. A. Ashrafyan

    2015-01-01

    Full Text Available In spite of all of modern medicine»s advances, ovarian cancer (OC mortality remains to be incommensurably high and to hold the lead among gynecological cancers. The initial cause of this deplorable statistics is the absence of a clear concept of the pathogenesis of OC and hence the justified prevention and methodology of early diagnosis of the disease; in this connection, therapy that proves to be ineffective is frequently used by medical oncologists in their daily practice. As a consequence, there is a high proportion of its further progression: the rates of early and late recurrences were about 30 and 60–65 %, respectively; most of which are drug resistant to further chemotherapy cycles. By taking into account these strikingly modest statistics, it becomes apparent that oncologists desire to make changes in the existing treatment regimen to achieve meaningful results. To use target drugs is one of these promising areas owing to new views on the concept of the pathogenesis of OC.Nevertheless, considering a wide variety of the signaling cascades and molecules, which are involved in the process of carcinogenesis, even target compounds, if they have only one point of application, cannot always produce their desirable therapeutic effect and their co-administration is responsible for high toxicity. In this light, the most effective drugs are indole-3-carbinol and epigallocathechin-3-gallate, which virtually cause no adverse reactions and can block various molecular targets at different levels of the mechanism of malignant transformation. Based on L. A. Ashrafyan, s concept of two pathogenetic variants of sporadic OC (2009 and on the recent findings in molecular biology and epigenetics, the incorporation of the above medications into the standard treatment regimen for OC should increase survival rates and change the nature of recurrence by that of more locally advanced forms. On this basis, a clinical trial was carried out to study

  16. 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...

  17. Hormonal Risk Factors for Ovarian Cancer in Premenopausal and Postmenopausal Women

    OpenAIRE

    Moorman, Patricia G.; Calingaert, Brian; Palmieri, Rachel T; Iversen, Edwin S.; Bentley, Rex C.; Halabi, Susan; Berchuck, Andrew; Joellen M Schildkraut

    2008-01-01

    Ovarian cancer is most frequently diagnosed in postmenopausal women; however, the strongest risk predictors, pregnancy and oral contraceptive use, occur in most women in their twenties and thirties. Relatively few studies have examined how reproductive risk factors vary between pre- and postmenopausal ovarian cancer. The authors used data from a population-based, case-control study of ovarian cancer (896 cases, 967 controls) conducted in North Carolina from 1999 to 2006. Odds ratios and 95% c...

  18. Risk and prognosis of ovarian cancer in women with endometriosis: a meta-analysis

    OpenAIRE

    Kim, H S; Kim, T. H.; Chung, H H; Song, Y. S.

    2014-01-01

    Background: The risk and prognosis of ovarian cancer have not been well established in women with endometriosis. Thus, we investigated the impact of endometriosis on the risk and prognosis for ovarian cancer, and evaluated clinicopathologic characteristics of endometriosis-associated ovarian cancer (EAOC) in comparison with non-EAOC. Methods: After we searched an electronic search to identify relevant studies published online between January 1990 and December 2012, we found 20 case–control an...

  19. 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...

  20. Markers of inflammation and risk of ovarian cancer in Los Angeles County

    OpenAIRE

    Wu, Anna H.; Pearce, Celeste; Tseng, Chiu-Chen; Templeman, Claire; Pike, Malcolm C.

    2009-01-01

    Factors that increase inflammation have been suggested to influence the development of ovarian cancer, but these factors have not been well studied. To further investigate this question we studied the role of talc use, history of endometrioisis, and use of non-steroidal anti-inflammatory drugs (NSAIDs) and risk of ovarian cancer in a population-based case-control study in Los Angeles County involving 609 women with newly diagnosed epithelial ovarian cancer and 688 population-based control wom...

  1. Dairy consumption and ovarian cancer risk in the Netherlands Cohort Study on diet and cancer

    OpenAIRE

    Mommers, M.; Schouten, L J; Goldbohm, R. A.; Brandt, P.A. van den

    2006-01-01

    Ovary cancer risk in relation to consumption of dairy products was investigated using a self-administered questionnaire on dietary habits and other risk factors for cancer, which was completed in 1986 by 62 573 postmenopausal women participating in the Netherlands Cohort Study. Follow-up for cancer was implemented by annual record linkage with the Netherlands Cancer Registry and a nationwide pathology registry. After 11.3 years of follow-up, data of 252 incident epithelial ovarian cancer case...

  2. Dermatomyositis as a paraneoplastic phenomenon in ovarian cancer.

    Science.gov (United States)

    Arshad, Ilyas; Barton, Desmond

    2016-01-01

    A 60-year-old woman diagnosed with papillary serous ovarian cancer had Klean-Prep and MRI contrast preoperatively. Afterwards, she developed swelling and an urticarial rash around her eye as she proceeded to have planned debulking surgery. Postoperatively the swelling and rash had spread over her face, neck, back and chest. Dermatology advised a possible allergy to Klean-Prep and MRI contrast. Subsequently over the next few months, the patient became severely debilitated from proximal myopathy of the upper and lower limbs, suffered severe pain restricting mobility and small bowel obstruction. Medical oncologist reviewed the patient, clinically diagnosed dermatomyositis and initiated treatment with high-dose intravenous steroids, resulting in remission of the patient's condition. The main purpose of this study is to describe the severity, diagnostic challenges and underline the clinical significance of dermatomyositis manifestations as a paraneoplastic effect in patients with ovarian cancer. PMID:27402586

  3. 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.

  4. [Ultrasound semiotics in recurrent ovarian cancer after optimal cytoreductive surgery].

    Science.gov (United States)

    Baklanova, N S; Kolomiets, L A; Frolova, I G; Viatkina, N V; Krasil'nikov, S É

    2014-01-01

    Features of ultrasound picture of morphologically verified recurrence of ovarian cancer in 21 patients are presented, who received combined treatment including cytoreductive surgery in the form of hysterectomy with oophorectomy, resection of the greater omentum and 6 courses of chemotherapy CAP for ovarian cancer stage III (FIGO). In all patients cytoreductive surgery was optimal--without residual tumor. Recurrence of the disease was detected in 12-48 months in 80.9% of the cases. Three variants of recurrence was revealed by ultrasonography: isolated peritoneal dissemination, in 14.2% of the cases, which was mainly detected during the first 12 months; single entities in the projection of the small pelvis (61.9%) and mixed form (local lesions of small pelvis and peritoneal dissemination) in 23.8% of the cases. PMID:25033684

  5. [Ultrasound semiotics in recurrent ovarian cancer after optimal cytoreductive surgery].

    Science.gov (United States)

    Baklanova, N S; Kolomiets, L A; Frolova, I G; Viatkina, N V; Krasil'nikov, S É

    2014-01-01

    Features of ultrasound picture of morphologically verified recurrence of ovarian cancer in 21 patients are presented, who received combined treatment including cytoreductive surgery in the form of hysterectomy with oophorectomy, resection of the greater omentum and 6 courses of chemotherapy CAP for ovarian cancer stage III (FIGO). In all patients cytoreductive surgery was optimal--without residual tumor. Recurrence of the disease was detected in 12-48 months in 80.9% of the cases. Three variants of recurrence was revealed by ultrasonography: isolated peritoneal dissemination, in 14.2% of the cases, which was mainly detected during the first 12 months; single entities in the projection of the small pelvis (61.9%) and mixed form (local lesions of small pelvis and peritoneal dissemination) in 23.8% of the cases.

  6. Fruits and vegetables and ovarian cancer risk in a pooled analysis of 12 cohort studies

    NARCIS (Netherlands)

    Koushik, A.; Hunter, D.J.; Spiegelman, D.; Anderson, K.E.; Arslan, A.A.; Beeson, W.L.; Brandt, P.A. van den; Buring, J.E.; Cerhan, J.R.; Colditz, G.A.; Fraser, G.E.; Freudenheim, J.L.; Genkinger, J.M.; Goldbohm, R.A.; Hankinson, S.E.; Koenig, K.L.; Larsson, S.C.; Leitzmann, M.; McCullough, M.L.; Miller, A.B.; Patel, A.; Rohan, T.E.; Schatzkin, A.; Smit, E.; Willett, W.C.; Wolk, A.; Zhang, S.M.; Smith-Warner, S.A.

    2005-01-01

    Because fruits and vegetables are rich in bioactive compounds with potential cancer-preventive actions, increased consumption may reduce the risk of ovarian cancer. Evidence on the association between fruit and vegetable intake and ovarian cancer risk has not been consistent. We analyzed and pooled

  7. Immunologic aspect of ovarian cancer and p53 as tumor antigen

    NARCIS (Netherlands)

    Nijman, HW; Lambeck, A; van der Burg, SH; van der Zee, AGJ; Daemen, T

    2005-01-01

    Ovarian cancer represents the fifth leading cause of death from all cancers for women. During the last decades overall survival has improved due to the use of new chemotherapy schedules. Still, the majority of patients die of this disease. Research reveals that ovarian cancer patients exhibit signif

  8. Association of family risk and lifestyle/comorbidities in ovarian cancer patients

    NARCIS (Netherlands)

    Teixeira, Natalia; Azevedo Koike Folgueira, Maria Aparecida; Maistro, Simone; Encinas, Giselly; de Bock, Geertruida Hendrika; Estevez Diz, Maria Del Pilar

    2015-01-01

    Objectives: to analyze factors that might indicate familial predisposition for ovarian cancer in patients diagnosed with this disease. Methods: in a prospective single center cohort study at the Institute of Cancer of the State of Sao Paulo (ICESP), 51 women diagnosed with ovarian cancer were includ

  9. Distinct prognostic values of four-Notch-receptor mRNA expression in ovarian cancer.

    Science.gov (United States)

    Zhou, Xinling; Teng, Lingling; Wang, Min

    2016-05-01

    Notch signaling pathway includes ligands and Notch receptors, which are frequently deregulated in several human malignancies including ovarian cancer. Aberrant activation of Notch signaling has been linked to ovarian carcinogenesis and progression. In the current study, we used the "Kaplan-Meier plotter" (KM plotter) database, in which updated gene expression data and survival information from a total of 1306 ovarian cancer patients were used to access the prognostic value of four Notch receptors in ovarian cancer patients. Hazard ratio (HR), 95 % confidence intervals, and log-rank P were calculated. Notch1 messenger RNA (mRNA) high expression was not found to be correlated to overall survival (OS) for all ovarian cancer, as well as in serous and endometrioid cancer patients followed for 20 years. However, Notch1 mRNA high expression is significantly associated with worsen OS in TP53 wild-type ovarian cancer patients, while it is significantly associated with better OS in TP53 mutation-type ovarian cancer patients. Notch2 mRNA high expression was found to be significantly correlated to worsen OS for all ovarian cancer patients, as well as in grade II ovarian cancer patients. Notch3 mRNA high expression was found to be significantly correlated to better OS for all ovarian cancer patients, but not in serous cancer patients and endometrioid cancer patients. Notch4 mRNA high expression was not found to be significantly correlated to OS for all ovarian cancer patients, serous cancer patients, and endometrioid cancer patients. These results indicate that there are distinct prognostic values of four Notch receptors in ovarian cancer. This information will be useful for better understanding of the heterogeneity and complexity in the molecular biology of ovarian cancer and for developing tools to more accurately predict their prognosis. Based on our results, Notch1 could be a potential drug target of TP53 wild-type ovarian cancer and Notch2 could be a potential drug

  10. Vaccine Therapy and Cyclophosphamide in Treating Patients With Stage II-III Breast or Stage II-IV Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

    Science.gov (United States)

    2016-01-07

    Recurrent Breast Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage IIA Breast Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIB Breast Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIIA Breast Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Breast Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Breast 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

  11. Targeting Signaling Pathways in Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Johannes Haybaeck

    2013-05-01

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

  12. Diagnosis and Management of Peritoneal Metastases from Ovarian Cancer

    OpenAIRE

    Evgenia Halkia; John Spiliotis; Paul Sugarbaker

    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 intraper...

  13. A genome-wide association study identifies susceptibility loci for ovarian cancer at 2q31 and 8q24

    DEFF Research Database (Denmark)

    Goode, Ellen L; Chenevix-Trench, Georgia; Song, Honglin;

    2010-01-01

    Ovarian cancer accounts for more deaths than all other gynecological cancers combined. To identify common low-penetrance ovarian cancer susceptibility genes, we conducted a genome-wide association study of 507,094 SNPs in 1,768 individuals with ovarian cancer (cases) and 2,354 controls, with foll...

  14. 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...

  15. Ovarian cancer risk factors by tumor dominance, a surrogate for cell of origin

    OpenAIRE

    Kotsopoulos, Joanne; Terry, Kathryn Lynne; Poole, Elizabeth M.; Rosner, Bernard Alfred; Murphy, Megan A.; Hecht, Jonathan Lewis; Crum, Christopher Paul; Missmer, Stacey Ann; Cramer, Daniel William; Tworoger, Shelley Slate

    2013-01-01

    Differentiating ovarian tumors based on developmental pathway may further our understanding of the disease. Traditionally, ovarian cancers were thought to arise from the ovarian surface epithelium; however, recent evidence suggests some tumors originate in the fallopian tube. We classified cases in a population-based case-control study (NECC) and two cohort studies (NHS/NHSII) by tumor dominance, a proxy for tissue of origin. Dominant tumors (likely ovarian origin) are restricted to one ovary...

  16. A Decision Tree Based Classifier to Analyze Human Ovarian Cancer cDNA Microarray Datasets.

    Science.gov (United States)

    Tsai, Meng-Hsiun; Wang, Hsin-Chieh; Lee, Guan-Wei; Lin, Yi-Chen; Chiu, Sheng-Hsiung

    2016-01-01

    Ovarian cancer is the deadliest gynaecological disease because of the high mortality rate and there is no any symptom in cancer early stage. It was often the terminal cancer period when patients were diagnosed with ovarian cancer and thus delays a good opportunity of treatment. The current common method for detecting ovarian cancer is blood testing for analyzing the tumor marker CA-125 of serum. However, specificity and sensitivity of CA-125 are insufficient for early detection. Therefore, it has become an urgent issue to look for an efficient method which precisely detects the tumor markers for ovarian cancer. This study aims to find the target genes of ovarian cancer by different algorithms of information science. Feature selection and decision tree were applied to analyze 9600 ovarian cancer-related genes. After screening the target genes, candidate genes will be analyzed by Ingenuity Pathway Analysis (IPA) software to create a genetic pathway model and to understand the interactive relationship in the different pathological stages of ovarian cancer. Finally, this research found 9 oncogenes associated with ovarian cancer and some genes had not been discovered in previous studies. This system will assist medical staffs in diagnosis and treatment at cancer early stage and improve the patient's survival. PMID:26531754

  17. Ovarian Metastasis from Lung Cancer: A Rare Entity

    Directory of Open Access Journals (Sweden)

    Huseyin Cengiz

    2013-01-01

    Full Text Available This paper describes a case of ovarian metastasis from lung carcinoma along with its diagnostic challenges, clinical management, and review of the literature. A 49-year-old woman was admitted to our emergency department with complaints of abdominal pain and vomiting. A laparoscopic appendectomy was performed due to acute appendicitis, and a unilateral oophorectomy (left side via laparoscopy was performed due to the detection of an ovarian mass. Immunohistochemical staining of the ovarian mass revealed that it was reactive to cytokeratin-7 (CK-7 but negative for CK-20. The immunohistochemical and pathological features of the tumor indicated an ovarian metastasis of non-small-cell lung cancer. The patient underwent chemotherapy and was followed up by the oncology department. Her postoperative regular followup of 6 months showed that her condition was stable with no recurrence. The management of female patients with acute abdominal pain and pelvic masses should consist of a multidisciplinary approach to include the diagnosis of any distant organ metastasis.

  18. Claudin-containing exosomes in the peripheral circulation of women with ovarian cancer

    International Nuclear Information System (INIS)

    The absence of highly sensitive and specific serum biomarkers makes mass screening for ovarian cancer impossible. The claudin proteins are frequently overexpressed in ovarian cancers, but their potential as prognostic, diagnostic, or detection markers remains unclear. Here, we have explored the possible use of these proteins as screening biomarkers for ovarian cancer detection. Claudin protein shedding from cells was examined by immunoblotting of conditioned culture media. The presence of claudins in exosomes released from ovarian cancer cells was demonstrated by sucrose gradient separation and immunogold electron microscopy experiments. Claudin-4-containing exosomes in the plasma of ovarian cancer patients were evaluated in a pilot panel of 63 ovarian cancer patients and 50 healthy volunteers. The CA125 marker was also assessed in these samples and compared with claudin-4 positivity. We show that full-length claudins can be shed from ovarian cancer cells in culture and found in the media as part of small lipid vesicles known as exosomes. Moreover, 32 of 63 plasma samples from ovarian cancer patients exhibited the presence of claudin-4-containing exosomes. In contrast, only one of 50 samples from individuals without cancer exhibited claudin-4-positive exosomes. In our small panel, at a specificity of 98%, the claudin-4 and CA125 tests had sensitivities of 51% and 71%, respectively. The two tests did not appear to be independent and were strongly correlated. Our work shows for the first time that claudin-4 can be released from ovarian cancer cells and can be detected in the peripheral circulation of ovarian cancer patients. The development of sensitive assays for the detection of claudin-4 in blood will be crucial in determining whether this approach can be useful, alone or in combination with other screening methods, for the detection of ovarian cancer

  19. Claudin-containing exosomes in the peripheral circulation of women with ovarian cancer

    Directory of Open Access Journals (Sweden)

    Bristow Robert E

    2009-07-01

    Full Text Available Abstract Background The absence of highly sensitive and specific serum biomarkers makes mass screening for ovarian cancer impossible. The claudin proteins are frequently overexpressed in ovarian cancers, but their potential as prognostic, diagnostic, or detection markers remains unclear. Here, we have explored the possible use of these proteins as screening biomarkers for ovarian cancer detection. Methods Claudin protein shedding from cells was examined by immunoblotting of conditioned culture media. The presence of claudins in exosomes released from ovarian cancer cells was demonstrated by sucrose gradient separation and immunogold electron microscopy experiments. Claudin-4-containing exosomes in the plasma of ovarian cancer patients were evaluated in a pilot panel of 63 ovarian cancer patients and 50 healthy volunteers. The CA125 marker was also assessed in these samples and compared with claudin-4 positivity. Results We show that full-length claudins can be shed from ovarian cancer cells in culture and found in the media as part of small lipid vesicles known as exosomes. Moreover, 32 of 63 plasma samples from ovarian cancer patients exhibited the presence of claudin-4-containing exosomes. In contrast, only one of 50 samples from individuals without cancer exhibited claudin-4-positive exosomes. In our small panel, at a specificity of 98%, the claudin-4 and CA125 tests had sensitivities of 51% and 71%, respectively. The two tests did not appear to be independent and were strongly correlated. Conclusion Our work shows for the first time that claudin-4 can be released from ovarian cancer cells and can be detected in the peripheral circulation of ovarian cancer patients. The development of sensitive assays for the detection of claudin-4 in blood will be crucial in determining whether this approach can be useful, alone or in combination with other screening methods, for the detection of ovarian cancer.

  20. 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....

  1. Quantitative proteomic analysis by iTRAQ® for the identification of candidate biomarkers in ovarian cancer serum

    Directory of Open Access Journals (Sweden)

    Higgins LeeAnn

    2010-06-01

    Full Text Available Abstract Background Ovarian cancer is the most lethal gynecologic malignancy, with the majority of cases diagnosed at an advanced stage when treatments are less successful. Novel serum protein markers are needed to detect ovarian cancer in its earliest stage; when detected early, survival rates are over 90%. The identification of new serum biomarkers is hindered by the presence of a small number of highly abundant proteins that comprise approximately 95% of serum total protein. In this study, we used pooled serum depleted of the most highly abundant proteins to reduce the dynamic range of proteins, and thereby enhance the identification of serum biomarkers using the quantitative proteomic method iTRAQ®. Results Medium and low abundance proteins from 6 serum pools of 10 patients each from women with serous ovarian carcinoma, and 6 non-cancer control pools were labeled with isobaric tags using iTRAQ® to determine the relative abundance of serum proteins identified by MS. A total of 220 unique proteins were identified and fourteen proteins were elevated in ovarian cancer compared to control serum pools, including several novel candidate ovarian cancer biomarkers: extracellular matrix protein-1, leucine-rich alpha-2 glycoprotein-1, lipopolysaccharide binding protein-1, and proteoglycan-4. Western immunoblotting validated the relative increases in serum protein levels for several of the proteins identified. Conclusions This study provides the first analysis of immunodepleted serum in combination with iTRAQ® to measure relative protein expression in ovarian cancer patients for the pursuit of serum biomarkers. Several candidate biomarkers were identified which warrant further development.

  2. Comparison of clinical efficacy of second look operation and FDG-PET scan in patients with ovarian cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Sang Young

    1999-12-01

    This study is to investigate whether FDG-PET scan can substitute for second look operation in patients with ovarian cancer showing complete response with chemotherapy. From Jan. 1999 to Oct. 1999, 10 patients with advanced ovarian cancer who showed clinical complete response with 6 cycles of combination chemotherapy were registered in KCCH. These patients showed no residual tumors in conventional radiologic imaging studies (CT or MRI), normal tumor marker, no evidence of disease by physical examination. PET scans and second look operation were performed in 10 patients with advanced ovarian cancer (3 patients with stage IIc, 2 patients with stage IIIb, 5 patients with IIIc), who showed complete response with cytoreductive surgery and 6 cycles of post-operative adjuvant cisplatin-based combination chemotherapy. Median age of patients was 45 years, and serous cystadenocarcinoma was most common histologic type. None showed active lesion in pelvis and abdomen with FDG-PET scan (SUV; > 3.5 kg/ml), and I patient showed active lesion in lung field. On second look operations, 5 patients (50%) showed positive result on multiple blind biopsy. The patient with active lesion on FDG-PET scan in lung field confirmed to have metastatic lesions by chest CT scan. In conclusion, FDG-PET scan is not useful for detection of small ovarian cancer lesions in pelvis and abdomen, and cannot substitute for second look operation to determine pathologic complete response.

  3. Symptom interpretation and health care seeking in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Blaakaer Jan

    2011-06-01

    Full Text Available Abstract Background Ovarian cancer is the leading cause of death among women suffering from gynaecological malignancies in the Western world. Worldwide, approximately 200,000 women are diagnosed with the disease each year. This article deals with the health care seeking and symptom interpretation process among Danish women, who have a very high mortality rate. Methods The health seeking and symptom interpretation process was analysed via combining study methods. The material consisted of registry data dealing with the use of public health care and hospital services of Danish women, newly diagnosed with ovarian cancer. These results were combined with findings from semi-structured qualitative research interviews on women's bodily experiences with symptom development. Results A number of 663 Danish women with ovarian cancer attended 27 different kinds of primary health care providers in a total of 14,009 visits during 2007. The women also had 6,214 contacts with various hospitals, and obtained 562 different diagnoses. From the main theme "Women's experiences with the onset of symptoms" three sub-themes were identified: "Bodily sensations", "From bodily sensation to symptom", and "Health seeking and treatment start". In all cases the General Practitioner represented the first contact to public health care, acting as gate-keeper to specialist and hospital referral. The women were major users of public health care throughout the diagnostic process and subsequent treatment. All women held personal knowledge concerning the onset of their symptoms. The early symptoms of ovarian cancer might be uncharacteristic and non-disease-specific when interpreted as personal experiences, but they had similarities when analysed together. Conclusions Diagnostic delay in ovarian cancer seems far from being exclusively a medical problem, as the delay proved to be influenced by organisational, cultural, and social factors, too. Initiatives facilitating the diagnostic

  4. Penetrance of breast cancer, ovarian cancer and contralateral breast cancer in BRCA1 and BRCA2 families : high cancer incidence at older age

    NARCIS (Netherlands)

    van der Kolk, Dorina M.; de Bock, Geertruida H.; Leegte, Beike K.; Schaapveld, Michael; Mourits, Marian J. E.; de Vries, J; van der Hout, Annemieke H.; Oosterwijk, Jan C.

    2010-01-01

    Accurate estimations of lifetime risks of breast and ovarian cancer are crucial for counselling women from BRCA1/2 families. We therefore determined breast and ovarian cancer penetrance in BRCA1/2 mutation families in the northern Netherlands and compared them with the incidence of cancers in the ge

  5. 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...

  6. Ovarian cancer standard of care:are there real alternatives?

    Institute of Scientific and Technical Information of China (English)

    Chiara Della Pepa; Giuseppe Tonini; Carmela Pisano; Marilena Di Napoli; Sabrina Chiara Cecere; Rosa Tambaro; Gaetano Facchini; Sando Pignata

    2015-01-01

    Ovarian cancer remains a major issue for gynecological oncologists, and most patients are diagnosed when the disease is already advanced with a poor chance of survival. Debulking surgery followed by platinum-taxane chemotherapy is the current standard of care, but based on several different strategies currently under evaluation, some encouraging data have been published in the last 4 to 5 years. This review provides a state-of-the-art overview of the available alternatives to conventional treatment and the most promising new combinations. For example, neoadjuvant chemotherapy does not seem to be inferior to primary debulking. Despite its outcome improvements, intraperitoneal chemotherapy struggles for acceptance due to the heavy toxicity. Dose-dense chemotherapy, after showing an impressive efficacy in Asian populations, has not produced equal results in a European cohort, and the results of alternative platinum doublets are not superior to those of carboplatin and paclitaxel. In this setting, adherence to a maintenance therapy after first-line treatment and multiple (primarily antiangiogenic) agents appears to be effective. Although many questions, including the duration of maintenance treatment and the use of bevacizumab beyond progression, remain unanswered, new biologic agents, such as poly(ADP-ribose) polymerase (PARP) inhibitors, nintedanib, and mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitors, have emerged as potential therapeutic options in the very near future. Based on the multiplicity of available strategies, the histological and molecular features of the tumor, in addition to patient’s clinical condition and disease state, continue to gain importance in guiding treatment choices.

  7. Analysis of diferentially expressed protein from primary and recurrent ovarian cancer serum

    Institute of Scientific and Technical Information of China (English)

    Yuan Wang; Jin-Jin Yu; Ting Zhu; Ling Xu; Ming Xu; Yu-Zheng Huang; Hong Pu; Chun-Qing Yu

    2012-01-01

    ABSTRACT Objective:To study the value of the differentially expressed proteins from primary and recurrent ovarian cancer serum for early diagnosis of primary and recurrent ovarian cancer.Methods:WCX kit(BrukerDaltonicsGraBH) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF-MS) technology were used to detect serum samples from49 patients with primary ovarian cancer and21 patients with recurrent disease.Results:In the mass range(Mr) from1000 to12000Da, eight differentially expressed protein peaks were screened from primary ovarian cancer serum.Among them, four protein peaks withMr1457,1857,2202, 7761 were lowly expressed and the others withMr2946,5333,5859,5901 were highly expressed. Ten diferentially expressed protein peaks were screened from recurrent ovarian cancer serum. Among them,1944,1980,2080,2661,2993,4450,4659,5359Da protein expressions were increased significantly, and1897,7868Da protein expressions were decreased significantly.The pattern of primary ovarian cancer was applied to8 early-stage ovarian cancer serum samples, and7 serum samples were successfully predicted with the accuracy of87.5%.The pattern of recurrent ovarian cancer was applied to9 without pelvic or abdominal mass recurrent ovarian cancer serum samples, and8 serum samples were successfully predicted with the accuracy of 88.9%.Conclusions:Combination ofMALDI-TOF-MS andWCX kit technology can directly screen the diferrential expressed protein from primary and recurrent ovarian cancer serum.They have clinical significance for enhancement of sensitivity and specificity of ovarian cancer diagnosis.

  8. KRAS Genomic Status Predicts the Sensitivity of Ovarian Cancer Cells to Decitabine | Office of Cancer Genomics

    Science.gov (United States)

    Decitabine, a cancer therapeutic that inhibits DNA methylation, produces variable antitumor response rates in patients with solid tumors that might be leveraged clinically with identification of a predictive biomarker. In this study, we profiled the response of human ovarian, melanoma, and breast cancer cells treated with decitabine, finding that RAS/MEK/ERK pathway activation and DNMT1 expression correlated with cytotoxic activity. Further, we showed that KRAS genomic status predicted decitabine sensitivity in low-grade and high-grade serous ovarian cancer cells.

  9. Towards Evidence-Based Management of Inherited Breast and Breast-Ovarian Cancer

    OpenAIRE

    Møller Pål

    2004-01-01

    Abstract Inherited breast-ovarian cancer was described in 1866. The underlying genetic defects in BRCA1/2 were demonstrated 128 years later. We now have 10 years of experience with genetic testing in BRCA kindreds. The majority of breast cancer kindreds (familial breast cancer) do not demonstrate ovarian cancer and are not associated with BRCA mutations. The effect of early diagnosis and treatment is monitored through international collaborations. BRCA1-associated breast cancer is biologicall...

  10. Discrimination analysis of mass spectrometry proteomics for ovarian cancer detection

    Institute of Scientific and Technical Information of China (English)

    Yan-jun HONG; Xiao-dan WANG; David SHEN; Su ZENG

    2008-01-01

    Aim:A discrimination analysis has been explored for the probabilistic classifica-tion of healthy versus ovarian cancer serum samples using proteomics data from mass spectrometry (MS).Methods:The method employs data normalization,clustering,and a linear discriminant analysis on surface-enhanced laser desorp-tion ionization (SELDI) time-of-flight MS data.The probabilistic classification method computes the optimal linear discriminant using the complex human blood serum SELDI spectra.Cross-validation and training/testing data-split experi-ments are conducted to verify the optimal discriminant and demonstrate the accu-racy and robustness of the method.Results:The cluster discrimination method achieves excellent performance.The sensitivity,specificity,and positive predic-tive values are above 97% on ovarian cancer.The protein fraction peaks,which significantly contribute to the classification,can be available from the analysis process.Conclusion:The discrimination analysis helps the molecular identities of differentially expressed proteins and peptides between the healthy and ovarian patients.

  11. Integrated analysis of germline and somatic variants in ovarian cancer.

    Science.gov (United States)

    Kanchi, Krishna L; Johnson, Kimberly J; Lu, Charles; McLellan, Michael D; Leiserson, Mark D M; Wendl, Michael C; Zhang, Qunyuan; Koboldt, Daniel C; Xie, Mingchao; Kandoth, Cyriac; McMichael, Joshua F; Wyczalkowski, Matthew A; Larson, David E; Schmidt, Heather K; Miller, Christopher A; Fulton, Robert S; Spellman, Paul T; Mardis, Elaine R; Druley, Todd E; Graubert, Timothy A; Goodfellow, Paul J; Raphael, Benjamin J; Wilson, Richard K; Ding, Li

    2014-01-01

    We report the first large-scale exome-wide analysis of the combined germline-somatic landscape in ovarian cancer. Here we analyse germline and somatic alterations in 429 ovarian carcinoma cases and 557 controls. We identify 3,635 high confidence, rare truncation and 22,953 missense variants with predicted functional impact. We find germline truncation variants and large deletions across Fanconi pathway genes in 20% of cases. Enrichment of rare truncations is shown in BRCA1, BRCA2 and PALB2. In addition, we observe germline truncation variants in genes not previously associated with ovarian cancer susceptibility (NF1, MAP3K4, CDKN2B and MLL3). Evidence for loss of heterozygosity was found in 100 and 76% of cases with germline BRCA1 and BRCA2 truncations, respectively. Germline-somatic interaction analysis combined with extensive bioinformatics annotation identifies 222 candidate functional germline truncation and missense variants, including two pathogenic BRCA1 and 1 TP53 deleterious variants. Finally, integrated analyses of germline and somatic variants identify significantly altered pathways, including the Fanconi, MAPK and MLL pathways. PMID:24448499

  12. Ovarian cancer and oral contraceptives: collaborative reanalysis of data from 45 epidemiological studies including 23,257 women with ovarian cancer and 87,303 controls

    DEFF Research Database (Denmark)

    Cancer, Collaborative Group on Epidemiological Studies of Ovarian; Beral, V.; Doll, R.;

    2008-01-01

    BACKGROUND: Oral contraceptives were introduced almost 50 years ago, and over 100 million women currently use them. Oral contraceptives can reduce the risk of ovarian cancer, but the eventual public-health effects of this reduction will depend on how long the protection lasts after use ceases. We...... aimed to assess these effects. METHODS: Individual data for 23,257 women with ovarian cancer (cases) and 87,303 without ovarian cancer (controls) from 45 epidemiological studies in 21 countries were checked and analysed centrally. The relative risk of ovarian cancer in relation to oral contraceptive use...... was estimated, stratifying by study, age, parity, and hysterectomy. FINDINGS: Overall 7308 (31%) cases and 32,717 (37%) controls had ever used oral contraceptives, for average durations among users of 4.4 and 5.0 years, respectively. The median year of cancer diagnosis was 1993, when cases were aged an average...

  13. Folate Intake and Methylenetetrahydrofolate Reductase Gene Polymorphisms as Predictive and Prognostic Biomarkers for Ovarian Cancer Risk

    Directory of Open Access Journals (Sweden)

    Ke Wang

    2012-03-01

    Full Text Available Folic acid and methylenetetrahydrofolate reductase (MTHFR may affect the development of human cancer. However, few studies have evaluated folate intake and MTHFR in susceptibility to and prognosis of patients with ovarian cancer. We conducted a prospective case-control study in 215 ovarian cancer patients and 218 controls (all Chinese between Jan. 2004 and Jan. 2007. MTHFR C677T genotyping was done by PCR-RFLP. All patients were followed up until Dec. 2010. We found a 2.43-fold increased risk of ovarian cancer among MTHFR 677TT carriers, and a decreased risk of ovarian cancer in individuals with high folate intake (OR = 0.54, 95% CI = 0.32–0.94. Cox regression survival analysis showed that among the ovarian cancer patients, those carrying the 677TT genotype had a higher risk of death (HR = 2.17, 95% CI = 1.20–4.79, while high folate intake was associated with a lower risk of death (HR = 0.43, 95% CI = 0.33–0.88. Moreover, MTHFR 677CC carriers with higher folate intake showed a lower risk of death from ovarian cancer (HR = 0.32, 95% CI = 0.27–0.82. In summary, high folate intake may lessen susceptibility and improve the prognosis of ovarian cancer patients, while the MTHFR 677TT genotype appears to increase ovarian cancer risk and worsen its prognosis in a Chinese population.

  14. 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

  15. Accumulation and toxicity of antibody-targeted doxorubicin-loaded PEG-PE micelles in ovarian cancer cell spheroid model.

    Science.gov (United States)

    Perche, Federico; Patel, Niravkumar R; Torchilin, Vladimir P

    2012-11-28

    We describe the evaluation of doxorubicin-loaded PEG-PE micelles targeting using an ovarian cancer cell spheroid model. Most ovarian cancer patients present at an advanced clinical stage and develop resistance to standard of care platinum/taxane therapy. Doxorubicin is also approved for ovarian cancer but had limited benefits in refractory patients. In this study, we used drug-resistant spheroid cultures of ovarian carcinoma to evaluate the uptake and cytotoxicity of an antibody-targeted doxorubicin formulation. Doxorubicin was encapsulated in polyethylene glycol-phosphatidyl ethanolamine (PEG-PE) conjugated micelles. The doxorubicin-loaded PEG-PE micelles (MDOX) were further decorated with a cancer cell-specific monoclonal 2C5 antibody to obtain doxorubicin-loaded immunomicelles (2C5-MDOX). Targeting and resulting toxicity of doxorubicin-loaded PEG-PE micelles were evaluated in three dimensional cancer cell spheroids. Superior accumulation of 2C5-MDOX compared to free doxorubicin or untargeted MDOX in spheroids was evidenced both by flow cytometry, fluorescence and confocal microscopy. Interestingly, even higher toxicity was measured by lactate dehydrogenase release and terminal deoxynucleotidyl transferase dUTP nick end labeling of targeted doxorubicin micelles in Bcl-2 overexpressing adriamycin-resistant spheroids. Overall, these results support use of spheroids to evaluate tumor targeted drug delivery. PMID:22974689

  16. YAP/TEAD co-activator regulated pluripotency and chemoresistance in ovarian cancer initiated cells.

    Directory of Open Access Journals (Sweden)

    Yan Xia

    Full Text Available Recent evidence suggests that some solid tumors, including ovarian cancer, contain distinct populations of stem cells that are responsible for tumor initiation, growth, chemo-resistance, and recurrence. The Hippo pathway has attracted considerable attention and some investigators have focused on YAP functions for maintaining stemness and cell differentiation. In this study, we successfully isolated the ovarian cancer initiating cells (OCICs and demonstrated YAP promoted self-renewal of ovarian cancer initiated cell (OCIC through its downstream co-activator TEAD. YAP and TEAD families were required for maintaining the expression of specific genes that may be involved in OCICs' stemness and chemoresistance. Taken together, our data first indicate that YAP/TEAD co-activator regulated ovarian cancer initiated cell pluripotency and chemo-resistance. It proposed a new mechanism on the drug resistance in cancer stem cell that Hippo-YAP signal pathway might serve as therapeutic targets for ovarian cancer treatment in clinical.

  17. Immunologic aspect of ovarian cancer and p53 as tumor antigen

    Directory of Open Access Journals (Sweden)

    van der Burg SH

    2005-09-01

    Full Text Available Abstract Ovarian cancer represents the fifth leading cause of death from all cancers for women. During the last decades overall survival has improved due to the use of new chemotherapy schedules. Still, the majority of patients die of this disease. Research reveals that ovarian cancer patients exhibit significant immune responses against their tumor. In this review the knowledge obtained thus far on the interaction of ovarian cancer tumor cells and the immune system is discussed. Furthermore the role of p53 as tumor antigen and its potential role as target antigen in ovarian cancer is summarized. Based on the increased knowledge on the role of the immune system in ovarian cancer major improvements are to be expected of immunotherapy based treatment of this disease.

  18. Study of the Molecular Recognition of Aptamers Selected through Ovarian Cancer Cell-SELEX

    OpenAIRE

    Dimitri Van Simaeys; Dalia López-Colón; Kwame Sefah; Rebecca Sutphen; Elizabeth Jimenez; Weihong Tan

    2010-01-01

    BACKGROUND: Ovarian cancer is the most lethal gynecological malignancy, and the ovarian clear cell carcinoma subtype (OCCA) demonstrates a particularly poor response to standard treatment. Improvements in ovarian cancer outcomes, especially for OCCA, could be expected from a clearer understanding of the molecular pathology that might guide strategies for earlier diagnosis and more effective treatment. METHODOLOGY/PRINCIPAL FINDINGS: Cell-SELEX technology was employed to develop new molecular ...

  19. Expression and histopathological correlation of CCR9 and CCL25 in ovarian cancer

    OpenAIRE

    Singh, Rajesh; Cecil R. Stockard; Grizzle, William E.; Lillard, James W.; Singh, Shailesh

    2011-01-01

    Ovarian carcinoma is the most lethal gynecological malignancy among women and its poor prognosis is mainly due to metastasis. Chemokine receptor CCR9 is primarily expressed by a small subset of immune cells. The interactions between CCL25 and CCR9 have been implicated in leukocyte trafficking to the small bowel, a frequent metastatic site for ovarian cancer cells. We have previously shown that ovarian cancer cells express CCR9 and play an important role in cell migration, invasion and surviva...

  20. Cigarette smoking and risk of ovarian cancer: a pooled analysis of 21 case-control studies

    OpenAIRE

    Faber, Mette T.; Kjær, Susanne K.; Dehlendorff, Christian; Chang-Claude, Jenny; Klaus K. Andersen; Høgdall, Estrid; Webb, Penelope M.; Jordan, Susan J; Rossing, Mary Anne; Doherty, Jennifer A; Lurie, Galina; Pamela J Thompson; Carney, Michael E; Goodman, Marc T.; Ness, Roberta B.

    2013-01-01

    Purpose 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. Methods We used data from 21 case–control studies of ovarian cancer (19,066...

  1. 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,...

  2. [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

  3. Prostate Cancer Susceptibility Polymorphism rs2660753 Is Not Associated with Invasive Ovarian Cancer

    DEFF Research Database (Denmark)

    Amankwah, Ernest K; Kelemen, Linda E; Wang, Qinggang;

    2011-01-01

    BACKGROUND: We previously reported an association between rs2660753, a prostate cancer susceptibility polymorphism, and invasive epithelial ovarian cancer (EOC; OR = 1.2, 95% CI=1.0-1.4, P(trend) = 0.01) that showed a stronger association with the serous histological subtype (OR = 1.3, 95% CI = 1.......1-1.5, P(trend) = 0.003). METHODS: We sought to replicate this association in 12 other studies comprising 4,482 cases and 6,894 controls of white non-Hispanic ancestry in the Ovarian Cancer Association Consortium. RESULTS: No evidence for an association with all cancers or serous cancers was observed.......0-1.2, P(trend) = 0.11). There was no evidence for statistical heterogeneity in ORs across the studies. CONCLUSIONS: Although rs2660753 is a strong prostate cancer susceptibility polymorphism, the association with another hormonally related cancer, invasive EOC, is not supported by this replication study...

  4. Prostate Cancer Susceptibility Polymorphism rs2660753 Is Not Associated with Invasive Ovarian Cancer

    DEFF Research Database (Denmark)

    Amankwah, Ernest K; Kelemen, Linda E; Wang, Qinggang;

    2011-01-01

    BACKGROUND: We previously reported an association between rs2660753, a prostate cancer susceptibility polymorphism, and invasive epithelial ovarian cancer (EOC; OR = 1.2, 95% CI=1.0-1.4, P(trend) = 0.01) that showed a stronger association with the serous histological subtype (OR = 1.3, 95% CI = 1.......0-1.2, P(trend) = 0.11). There was no evidence for statistical heterogeneity in ORs across the studies. CONCLUSIONS: Although rs2660753 is a strong prostate cancer susceptibility polymorphism, the association with another hormonally related cancer, invasive EOC, is not supported by this replication study.......1-1.5, P(trend) = 0.003). METHODS: We sought to replicate this association in 12 other studies comprising 4,482 cases and 6,894 controls of white non-Hispanic ancestry in the Ovarian Cancer Association Consortium. RESULTS: No evidence for an association with all cancers or serous cancers was observed...

  5. 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.

  6. 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...

  7. 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

  8. 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.

  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. Three new potential ovarian cancer biomarkers detected in human urine with equalizer bead technology

    DEFF Research Database (Denmark)

    Petri, Anette Lykke; Simonsen, Anja Hviid; Yip, Tai-Tung;

    2008-01-01

    OBJECTIVE: To examine whether urine can be used to measure specific ovarian cancer proteomic profiles and whether one peak alone or in combination with other peaks or CA125 has the sensitivity and specificity to discriminate between ovarian cancer pelvic mass and benign pelvic mass. METHODS: A to...

  11. TXNDC17 promotes paclitaxel resistance via inducing autophagy in ovarian cancer.

    Science.gov (United States)

    Zhang, Song-Fa; Wang, Xin-Yu; Fu, Zhi-Qin; Peng, Qiao-Hua; Zhang, Jian-Yang; Ye, Feng; Fu, Yun-Feng; Zhou, Cai-Yun; Lu, Wei-Guo; Cheng, Xiao-Dong; Xie, Xing

    2015-01-01

    Paclitaxel is recommended as a first-line chemotherapeutic agent against ovarian cancer, but drug resistance becomes a major limitation of its success clinically. The key molecule or mechanism associated with paclitaxel resistance in ovarian cancer still remains unclear. Here, we showed that TXNDC17 screened from 356 differentially expressed proteins by LC-MS/MS label-free quantitative proteomics was more highly expressed in paclitaxel-resistant ovarian cancer cells and tissues, and the high expression of TXNDC17 was associated with poorer prognostic factors and exhibited shortened survival in 157 ovarian cancer patients. Moreover, paclitaxel exposure induced upregulation of TXNDC17 and BECN1 expression, increase of autophagosome formation, and autophagic flux that conferred cytoprotection for ovarian cancer cells from paclitaxel. TXNDC17 inhibition by siRNA or enforced overexpression by a pcDNA3.1(+)-TXNDC17 plasmid correspondingly decreased or increased the autophagy response and paclitaxel resistance. Additionally, the downregulation of BECN1 by siRNA attenuated the activation of autophagy and cytoprotection from paclitaxel induced by TXNDC17 overexpression in ovarian cancer cells. Thus, our findings suggest that TXNDC17, through participation of BECN1, induces autophagy and consequently results in paclitaxel resistance in ovarian cancer. TXNDC17 may be a potential predictor or target in ovarian cancer therapeutics.

  12. Milk, yogurt, and lactose intake and ovarian cancer risk: a meta-analysis.

    Science.gov (United States)

    Liu, Jing; Tang, Wenru; Sang, Lei; Dai, Xiaoli; Wei, Danping; Luo, Ying; Zhang, Jihong

    2015-01-01

    Inconclusive information for the role of dairy food intake in relation to ovarian cancer risk may associate with adverse effects of lactose, which has been hypothesized to increase gonadotropin levels in animal models and ecological studies. Up to now, several studies have indicated the association between dairy food intake and risk of ovarian cancer, but no identified founding was reported. We performed this meta-analysis to derive a more precise estimation of the association between dairy food intake and ovarian cancer risk. Using the data from 19 available publications, we examined dairy food including low-fat/skim milk, whole milk, yogurt and lactose in relation to risk of ovarian cancer by meta-analysis. Pooled odds ratio (OR) with 95% confidence interval (CI) were used to assess the association. We observed a slightly increased risk of ovarian cancer with high intake of whole milk, but has no statistical significance (OR = 1.228, 95% CI = 1.031-1.464, P = 0.022). The results of other milk models did not provide evidence of positive association with ovarian cancer risk. This meta-analysis suggests that low-fat/skim milk, whole milk, yogurt and lactose intake has no associated with increased risk of ovarian cancer. Further studies with larger participants worldwide are needed to validate the association between dairy food intake and ovarian cancer.

  13. Correlation of Bmi-1 expression and telomerase activity in human ovarian cancer

    NARCIS (Netherlands)

    Zhang, F. B.; Sui, L. H.; Xin, T.

    2008-01-01

    This study investigates the correlation between the oncoprotein Bmi-1 and telomerase activity in ovarian cancer. A real-time polymerase chain reaction (PCR) method is used to detect the messenger RNA (mRNA) expression of Bmi-1 protein in 47 ovarian epithelial cancer cases, and immunohistochemistry i

  14. Reproductive and hormonal factors, and ovarian cancer risk for BRCA1 and BRCA2 mutation carriers:

    DEFF Research Database (Denmark)

    Antoniou, Antonis C; Rookus, Matti; Andrieu, Nadine;

    2009-01-01

    BACKGROUND: Several reproductive and hormonal factors are known to be associated with ovarian cancer risk in the general population, including parity and oral contraceptive (OC) use. However, their effect on ovarian cancer risk for BRCA1 and BRCA2 mutation carriers has only been investigated in a...

  15. Risk of Ovarian Cancer and the NF-κB Pathway

    DEFF Research Database (Denmark)

    Charbonneau, Bridget; Block, Matthew S; Bamlet, William R;

    2014-01-01

    A missense single-nucleotide polymorphism (SNP) in the immune modulatory gene IL1A has been associated with ovarian cancer risk (rs17561). Although the exact mechanism through which this SNP alters risk of ovarian cancer is not clearly understood, rs17561 has also been associated with risk of end...

  16. CYTOTOXIC T-LYMPHOCYTE IMMUNOTHERAPY FOR OVARIAN CANCER: A PILOT STUDY

    OpenAIRE

    Wright, Stephen E.; Rewers-Felkins, Kathleen A.; Quinlin, Imelda S.; Phillips, Catherine A.; Townsend, Mary; Philip, Ramila; Dobrzanski, Mark J.; Lockwood-Cooke, Pamela R.; Robinson, William

    2012-01-01

    The objective was to evaluate the toxicity and feasibility of intraperitoneal (IP) infusion of tumor-specific cytotoxic T-lymphocytes (CTL) as therapy for recurrent ovarian cancer, and to determine if repetitive cycles of CTL generation and infusion measurably increases the host’s ovarian cancer immune response.

  17. Patterns of spread of clear cell ovarian cancer: Case report and case series ☆

    OpenAIRE

    Kumar, Aalok; Gilks, C. Blake; Mar, Colin; Santos, Jennifer; Tinker, Anna V.

    2013-01-01

    Highlights • Although patterns of metastases in ovarian clear cell cancer are not well described, patients may initially present with bone metastases. • Clear cell carcinoma with bone metastases is responsive to radiation therapy. • Bone metastases are not common in patients with ovarian high grade serous cancer.

  18. Consumption of dietary fat and meat and risk of ovarian cancer in the Netherlands Cohort Study

    NARCIS (Netherlands)

    Gilsing, A.M.J.; Weijenberg, M.P.; Goldbohm, R.A.; Brandt, P.A. van den; Schouten, L.J.

    2011-01-01

    Background: Evidence that links dietary factors to ovarian cancer is conflicting, but several epidemiologic studies suggested that consumption of dietary fat and meat may increase risk of ovarian cancer. Objective: We studied associations of intakes of total fat and sources and subtypes of fat, fres

  19. Nrf2, the master redox switch : The Achilles' heel of ovarian cancer?

    NARCIS (Netherlands)

    van der Wijst, Monique G. P.; Brown, Robert; Rots, Marianne G.

    2014-01-01

    Ovarian cancer is the most lethal gynecological tumor type in the world due to late stage detection, and resistance to chemotherapy. Therefore, alternative additional therapies are required. The etiology of ovarian cancer remains largely unknown, but risk factors point toward an important role for o

  20. DIFFERENTIAL DIAGNOSIS OF PRIMARY AND METASTATIC OVARIAN TUMORS IN PATIENTS WITH COLONIC CANCER

    Directory of Open Access Journals (Sweden)

    I. G. Komarov

    2013-01-01

    Full Text Available This report summarizes existing data on differential diagnosis between primary and metastatic ovarian cancer in patients with colorectal cancer (CRC. The results obtained in N.N. Blokhin Russian Cancer Research Center on the management of this malignancy are also presented. The evidence in favour of the need of genetic counseling and monitoring of the patients with aggravated familial history for early diagnosis of synchronous and metachronous ovarian cancer in patients with CRC is produced. A number of clinical, laboratory and diagnostic methods in addition to immunohistology and molecular genetics should be used for differential diagnosis of primary and metastatic ovarian cancer in patients with CRC.

  1. Type-specific cell line models for type-specific ovarian cancer research.

    Directory of Open Access Journals (Sweden)

    Michael S Anglesio

    Full Text Available BACKGROUND: OVARIAN CARCINOMAS CONSIST OF AT LEAST FIVE DISTINCT DISEASES: high-grade serous, low-grade serous, clear cell, endometrioid, and mucinous. Biomarker and molecular characterization may represent a more biologically relevant basis for grouping and treating this family of tumors, rather than site of origin. Molecular characteristics have become the new standard for clinical pathology, however development of tailored type-specific therapies is hampered by a failure of basic research to recognize that model systems used to study these diseases must also be stratified. Unrelated model systems do offer value for study of biochemical processes but specific cellular context needs to be applied to assess relevant therapeutic strategies. METHODS: We have focused on the identification of clear cell carcinoma cell line models. A panel of 32 "ovarian cancer" cell lines has been classified into histotypes using a combination of mutation profiles, IHC mutation-surrogates, and a validated immunohistochemical model. All cell lines were identity verified using STR analysis. RESULTS: Many described ovarian clear cell lines have characteristic mutations (including ARID1A and PIK3CA and an overall molecular/immuno-profile typical of primary tumors. Mutations in TP53 were present in the majority of high-grade serous cell lines. Advanced genomic analysis of bona-fide clear cell carcinoma cell lines also support copy number changes in typical biomarkers such at MET and HNF1B and a lack of any recurrent expressed re-arrangements. CONCLUSIONS: As with primary ovarian tumors, mutation status of cancer genes like ARID1A and TP53 and a general immuno-profile serve well for establishing histotype of ovarian cancer cell We describe specific biomarkers and molecular features to re-classify generic "ovarian carcinoma" cell lines into type specific categories. Our data supports the use of prototype clear cell lines, such as TOV21G and JHOC-5, and questions the use of

  2. Molecular Subtyping of Serous Ovarian Tumors Reveals Multiple Connections to Intrinsic Breast Cancer Subtypes

    DEFF Research Database (Denmark)

    Jönsson, Jenny-Maria; Johansson, Ida; Dominguez-Valentin, Mev;

    2014-01-01

    with the well-established intrinsic molecular subtypes of breast cancer. METHODS: Global gene expression profiling using Illumina's HT12 Bead Arrays was applied to 59 fresh-frozen serous ovarian malignant, benign and borderline tumors. Nearest centroid classification was performed applying previously published...... to the luminal A breast cancer subtype. These findings remained when analyzed in an independent dataset, supporting links between the molecular subtypes of ovarian cancer and breast cancer beyond those recently acknowledged. CONCLUSIONS: These data link the transcriptional profiles of serous ovarian cancer...... to the intrinsic molecular subtypes of breast cancer, in line with the shared clinical and molecular features between high-grade serous ovarian cancer and basal-like breast cancer, and suggest that biomarkers and targeted therapies may overlap between these tumor subsets. The link between benign and borderline...

  3. Ovarian Cancer Screening Method Fails to Reduce Deaths from the Disease

    Science.gov (United States)

    New results from the NCI-sponsored PLCO Cancer Screening Trial show that screening for ovarian cancer with transvaginal ultrasound (TVU) and the CA-125 blood test did not result in fewer deaths from the disease compared with usual care.

  4. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for treatment of ovarian cancer.

    Science.gov (United States)

    Polom, Karol; Roviello, Giandomenico; Generali, Daniele; Marano, Luigi; Petrioli, Roberto; Marsili, Stefania; Caputo, Edda; Marrelli, Daniele; Roviello, Franco

    2016-05-01

    Hyperthermic intraperitoneal chemotherapy (HIPEC), a strategy combining maximal cytoreductive surgery and maximal regional chemotherapy, has been applied to treat ovarian cancer resulting in long-term survival rates in selected patients. However, the status of HIPEC in ovarian cancer remains an experimental procedure, given the many variables among the data and trials reviewed, to enable us to derive strong conclusions about its role from this overview. In this review we discuss treatment with HIPEC in patients with ovarian cancer and future prospective of its use in clinical setting. HIPEC is an effective tool in the treatment of selected patients with peritoneal carcinomatosis from ovarian cancer. Unfortunately, due to the lack of randomised trials, the evidence of HIPEC is very limited. Future randomised studies are awaited to define the role and clinical impact of HIPEC in ovarian cancer. PMID:26984715

  5. 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...

  6. Cancer stem cell marker CD90 inhibits ovarian cancer formation via β3 integrin

    Science.gov (United States)

    Chen, Wei-Ching; Hsu, Hui-Ping; Li, Chung-Yen; Yang, Ya-Ju; Hung, Yu-Hsuan; Cho, Chien-Yu; Wang, Chih-Yang; Weng, Tzu-Yang; Lai, Ming-Derg

    2016-01-01

    Cancer stem cell (CSC) markers have been identified for CSC isolation and proposed as therapeutic targets in various types of cancers. CD90, one of the characterized markers in liver and gastric cancer, is shown to promote cancer formation. However, the underexpression level of CD90 in ovarian cancer cells and the evidence supporting the cellular mechanism have not been investigated. In the present study, we found that the DNA copy number of CD90 is correlated with mRNA expression in ovarian cancer tissue and the ovarian cancer patients with higher CD90 have good prognosis compared to the patients with lower CD90. Although the expression of CD90 in human ovarian cancer SKOV3 cells enhances the cell proliferation by MTT and anchorage-dependent growth assay, CD90 inhibits the anchorage-independent growth ability in vitro and tumor formation in vivo. CD90 overexpression suppresses the sphere-forming ability and ALDH activity and enhances the cell apoptosis, indicating that CD90 may reduce the cell growth by the properties of CSC and anoikis. Furthermore, CD90 reduces the expression of other CSC markers, including CD133 and CD24. The inhibition of CD133 is attenuated by the mutant CD90, which is replaced with RLE domain into RLD domain. Importantly, the CD90-regulated inhibition of CD133 expression, anchorage-independent growth and signal transduction of mTOR and AMPK are restored by the β3 integrin shRNA. Our results provide evidence that CD90 mediates the antitumor formation by interacting with β3 integrin, which provides new insight that can potentially be applied in the development of therapeutic strategies in ovarian cancer. PMID:27633757

  7. Expression and histopathological correlation of CCR9 and CCL25 in ovarian cancer.

    Science.gov (United States)

    Singh, Rajesh; Stockard, Cecil R; Grizzle, William E; Lillard, James W; Singh, Shailesh

    2011-08-01

    Ovarian carcinoma is the most lethal gynecological malignancy among women and its poor prognosis is mainly due to metastasis. Chemokine receptor CCR9 is primarily expressed by a small subset of immune cells. The interactions between CCL25 and CCR9 have been implicated in leukocyte trafficking to the small bowel, a frequent metastatic site for ovarian cancer cells. We have previously shown that ovarian cancer cells express CCR9 and play an important role in cell migration, invasion and survival in the presence of its natural ligand in vitro. In this study, we have evaluated the expression of CCR9 and CCL25 in ovarian cancer cells and clinical samples. Ovarian cancer tissue microarrays from University of Alabama at Birmingham and AccuMax were stained for CCR9 and CCL25. Aperio ScanScope was used to acquire 80X digital images and expression analysis of CCR9 and CCL25. Flow cytometry and the Image stream system were used to conform the expression of CCR9 and CCL25 in ovarian cancer cells. Our results show significantly higher (ptumor, dysgerminoma, transitional cell carcinoma, Brenner tumor, yolk sac tumor, adenocarcinoma and fibroma cases, compared to non-neoplastic ovarian tissue. Similar to tissue expression, CCR9 was also significantly expressed by the ovarian cancer cell lines (OVCAR-3 and SK-OV-3) in comparison to normal adult ovarian epithelial cell. We provide the first evidence that CCR9 and its natural ligand CCL25 are highly expressed by ovarian cancer tissue and their expression correlates with histological subtypes. Expression of this chemokine receptor and its ligand CCL25 within primary tumor tissue further suggests a potential role of this chemokine-receptor axis in ovarian cancer progression. PMID:21637913

  8. Genetic variation on 9p22 is associated with abnormal ovarian ultrasound results in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

    Directory of Open Access Journals (Sweden)

    Nicolas Wentzensen

    Full Text Available BACKGROUND: A recent ovarian cancer genome-wide association study (GWAS identified a locus on 9p22 associated with reduced ovarian cancer risk. The single nucleotide polymorphism (SNP markers localize to the BNC2 gene, which has been associated with ovarian development. METHODS: We analyzed the association of 9p22 SNPs with transvaginal ultrasound (TVU screening results and CA-125 blood levels from participants without ovarian cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO; 1,106 women with adequate ultrasound screening results and available genotyping information were included in the study. RESULTS: We observed a significantly increased risk of abnormal suspicious TVU results for seven SNPs on 9p22, with odds ratios between 1.68 (95% CI: 1.04-2.72 for rs4961501 and 2.10 (95% CI: 1.31-3.38 for rs12379183. Associations were restricted to abnormal suspicious findings at the first TVU screen. We did not observe an association between 9p22 SNPs and CA-125 levels. CONCLUSIONS: Our findings suggest that 9p22 SNPs, which were found to be associated with decreased risk of ovarian cancer in a recent GWAS, are associated with sonographically detectable ovarian abnormalities. Our results corroborate the relevance of the 9p22 locus for ovarian biology. Further studies are required to understand the complex relationship between screening abnormalities and ovarian carcinogenesis and to evaluate whether this locus can influence the risk stratification of ovarian cancer screening.

  9. Glucocorticoid regulation of SLIT/ROBO tumour suppressor genes in the ovarian surface epithelium and ovarian cancer cells.

    Directory of Open Access Journals (Sweden)

    Rachel E Dickinson

    Full Text Available The three SLIT ligands and their four ROBO receptors have fundamental roles in mammalian development by promoting apoptosis and repulsing aberrant cell migration. SLITs and ROBOs have emerged as candidate tumour suppressor genes whose expression is inhibited in a variety of epithelial tumours. We demonstrated that their expression could be negatively regulated by cortisol in normal ovarian luteal cells. We hypothesised that after ovulation the locally produced cortisol would inhibit SLIT/ROBO expression in the ovarian surface epithelium (OSE to facilitate its repair and that this regulatory pathway was still present, and could be manipulated, in ovarian epithelial cancer cells. Here we examined the expression and regulation of the SLIT/ROBO pathway in OSE, ovarian cancer epithelial cells and ovarian tumour cell lines. Basal SLIT2, SLIT3, ROBO1, ROBO2 and ROBO4 expression was lower in primary cultures of ovarian cancer epithelial cells when compared to normal OSE (P<0.05 and in poorly differentiated SKOV-3 cells compared to the more differentiated PEO-14 cells (P<0.05. Cortisol reduced the expression of certain SLITs and ROBOs in normal OSE and PEO-14 cells (P<0.05. Furthermore blocking SLIT/ROBO activity reduced apoptosis in both PEO-14 and SKOV-3 tumour cells (P<0.05. Interestingly SLIT/ROBO expression could be increased by reducing the expression of the glucocorticoid receptor using siRNA (P<0.05. Overall our findings indicate that in the post-ovulatory phase one role of cortisol may be to temporarily inhibit SLIT/ROBO expression to facilitate regeneration of the OSE. Therefore this pathway may be a target to develop strategies to manipulate the SLIT/ROBO system in ovarian cancer.

  10. Secretome Identifies Tenascin-X as a Potent Marker of Ovarian Cancer

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    Marianne Kramer

    2015-01-01

    Full Text Available CA-125 has been a valuable marker for the follow-up of ovarian cancer patients but it is not sensitive enough to be used as diagnostic marker. We had already used secretomic methods to identify proteins differentially secreted by serous ovarian cancer cells compared to healthy ovarian cells. Here, we evaluated the secretion of these proteins by ovarian cancer cells during the follow-up of one patient. Proteins that correlated with CA-125 levels were screened using serum samples from ovarian cancer patients as well as benign and healthy controls. Tenascin-X secretion was shown to correlate with CA-125 value in the initial case study. The immunohistochemical detection of increased amount of tenascin-X in ovarian cancer tissues compared to healthy tissues confirms the potent interest in tenascin-X as marker. We then quantified the tenascin-X level in serum of patients and identified tenascin-X as potent marker for ovarian cancer, showing that secretomic analysis is suitable for the identification of protein biomarkers when combined with protein immunoassay. Using this method, we determined tenascin-X as a new potent marker for serous ovarian cancer.

  11. Detection of Mycoplasma Hyorhinis Infection in Ovarian Cancer with in situ Hybridization and Immunohistochemistry

    Institute of Scientific and Technical Information of China (English)

    Hua YANG; Jian-zhi ZHANG; Cheng-chao SHOU

    2010-01-01

    OBJECTIVE To detect Mycoplasma hyorhinis in ovarian cancer tissues and the relationship between mycoplasma infection and ovarian cancer. METHODS All specimens obtained from 109 cases with ovarian cancer were fixed in freshly prepared 10% neutral buffered formalin, embedded in paraffin, and cut into 4-μm sections for insitu hybridization (ISH) and then detected with immunohistochemistry (IHC). The expressions of 16S rRNA and P37 protein from mycoplasma hyorhinis were detected respectively using ISH and IHC. SPSS 13.0 so ware was employed to analyze the relationship between the results of the study and clinical pathological materials. RESULTS The expression rate of mycoplasma hyorhinis 16S rRNA gene and P37 protein was 20.2% (22/109) and 43.1% (47/109cases) in ovarian cancer tissues, respectively, but it was 0 (0/30cases) in the normal ovarian tissues. The difference in mycoplasma infection ratio between ovarian cancer tissues and normal tissues was extremely significant (P < 0.001). Anyhow, we didn't found any association between the mycoplasma infection and clinical pathological characters.CONCLUSION There was a mycoplasma infection in ovarian cancer tissues, which may play a role in oncogenesis of ovarian cancer.

  12. Coalition of Oct4A and β1 integrins in facilitating metastasis in ovarian cancer

    OpenAIRE

    Samardzija, Chantel; Luwor, Rodney B.; Quinn, Michael A; Kannourakis, George; Jock K Findlay; Ahmed, Nuzhat

    2016-01-01

    Background Ovarian cancer is a metastatic disease and one of the leading causes of gynaecology malignancy-related deaths in women. Cancer stem cells (CSCs) are key contributors of cancer metastasis and relapse. Integrins are a family of cell surface receptors which allow interactions between cells and their surrounding microenvironment and play a fundamental role in promoting metastasis. This study investigates the molecular mechanism which associates CSCs and integrins in ovarian cancer meta...

  13. Cell-cycle protein expression in a population-based study of ovarian and endometrial cancers

    OpenAIRE

    Felix, Ashley S.; Sherman, Mark E.; Hewitt, Stephen M.; Munira eGunja; Yang, Hannah P.; Renata eCora; Vicky eBoudreau; Kris eYlaya; Jolanta eLissowska; Brinton, Louise A.; Nicolas eWentzensen

    2015-01-01

    Aberrant expression of cyclin-dependent kinase (CDK) inhibitors is implicated in the carcinogenesis of many cancers, including ovarian and endometrial cancers. We examined associations between CDK inhibitor expression, cancer risk factors, tumor characteristics, and survival outcomes among ovarian and endometrial cancer patients enrolled in a population-based case control study. Expression (negative vs. positive) of three CDK inhibitors (p16, p21, p27) and ki67 was examined with immunohistoch...

  14. Cell-Cycle Protein Expression in a Population-Based Study of Ovarian and Endometrial Cancers

    OpenAIRE

    Felix, Ashley S.; Sherman, Mark E.; Hewitt, Stephen M.; Gunja, Munira Z.; Yang, Hannah P.; Cora, Renata L.; Boudreau, Vicky; Ylaya, Kris; Lissowska, Jolanta; Brinton, Louise A.; Wentzensen, Nicolas

    2015-01-01

    Aberrant expression of cyclin-dependent kinase (CDK) inhibitors is implicated in the carcinogenesis of many cancers, including ovarian and endometrial cancers. We examined associations between CDK inhibitor expression, cancer risk factors, tumor characteristics, and survival outcomes among ovarian and endometrial cancer patients enrolled in a population-based case-control study. Expression (negative vs. positive) of three CDK inhibitors (p16, p21, and p27) and ki67 was examined with immunohis...

  15. Endometriosis-Associated Ovarian Cancer: A Review of Pathogenesis

    Directory of Open Access Journals (Sweden)

    Shu-Wing Ng

    2013-03-01

    Full Text Available Endometriosis is classically defined as the presence of endometrial glands and stroma outside of the endometrial lining and uterine musculature. With an estimated frequency of 5%–10% among women of reproductive age, endometriosis is a common gynecologic disorder. While in itself a benign lesion, endometriosis shares several characteristics with invasive cancer, has been shown to undergo malignant transformation, and has been associated with an increased risk of epithelial ovarian carcinoma (EOC. Numerous epidemiologic studies have shown an increased risk of EOC among women with endometriosis. This is particularly true for women with endometrioid and clear cell ovarian carcinoma. However, the carcinogenic pathways by which endometriosis associated ovarian carcinoma (EAOC develops remain poorly understood. Current molecular studies have sought to link endometriosis with EAOC through pathways related to oxidative stress, inflammation and hyperestrogenism. In addition, numerous studies have sought to identify an intermediary lesion between endometriosis and EAOC that may allow for the identification of endometriosis at greatest risk for malignant transformation or for the prevention of malignant transformation of this common gynecologic disorder. The objective of the current article is to review the current data regarding the molecular events associated with EAOC development from endometriosis, with a primary focus on malignancies of the endometrioid and clear cell histologic sub-types.

  16. Integration and bioinformatics analysis of DNA-methylated genes associated with drug resistance in ovarian cancer

    Science.gov (United States)

    YAN, BINGBING; YIN, FUQIANG; WANG, QI; ZHANG, WEI; LI, LI

    2016-01-01

    The main obstacle to the successful treatment of ovarian cancer is the development of drug resistance to combined chemotherapy. Among all the factors associated with drug resistance, DNA methylation apparently plays a critical role. In this study, we performed an integrative analysis of the 26 DNA-methylated genes associated with drug resistance in ovarian cancer, and the genes were further evaluated by comprehensive bioinformatics analysis including gene/protein interaction, biological process enrichment and annotation. The results from the protein interaction analyses revealed that at least 20 of these 26 methylated genes are present in the protein interaction network, indicating that they interact with each other, have a correlation in function, and may participate as a whole in the regulation of ovarian cancer drug resistance. There is a direct interaction between the phosphatase and tensin homolog (PTEN) gene and at least half of the other genes, indicating that PTEN may possess core regulatory functions among these genes. Biological process enrichment and annotation demonstrated that most of these methylated genes were significantly associated with apoptosis, which is possibly an essential way for these genes to be involved in the regulation of multidrug resistance in ovarian cancer. In addition, a comprehensive analysis of clinical factors revealed that the methylation level of genes that are associated with the regulation of drug resistance in ovarian cancer was significantly correlated with the prognosis of ovarian cancer. Overall, this study preliminarily explains the potential correlation between the genes with DNA methylation and drug resistance in ovarian cancer. This finding has significance for our understanding of the regulation of resistant ovarian cancer by methylated genes, the treatment of ovarian cancer, and improvement of the prognosis of ovarian cancer. PMID:27347118

  17. The role of the tumor stroma in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Ben eDavidson

    2014-05-01

    Full Text Available The tumor microenvironment, consisting of stromal myofibroblasts, endothelial cells and leukocytes, is growingly perceived to be a major contributor to the pathogenesis and disease progression in practically all cancer types. Stromal myofibroblasts produce angiogenic factors, proteases, growth factors, immune response-modulating proteins, anti-apoptotic proteins and signaling molecules, and express surface receptors and respond to stimuli initiated in the tumor cells to establish a bi-directional communication network in the microenvironment to promote tumor cell invasion and metastasis. Many of these molecules are candidates for targeted therapy and the cancer stroma has been recently regarded as target for biological intervention. This review provides an overview of the biology and clinical role of the stroma in ovarian cancer.

  18. Multiple Miscarriages Are Associated with the Risk of Ovarian Cancer : Results from the European Prospective Investigation into Cancer and Nutrition

    NARCIS (Netherlands)

    Braem, Marieke G. M.; Onland-Moret, N. Charlotte; Schouten, Leo J.; Kruitwagen, Roy F. P. M.; Lukanova, Annekatrin; Allen, Naomi E.; Wark, Petra A.; Tjonneland, Anne; Hansen, Louise; Brauner, Christina Marie; Overvad, Kim; Clavel-Chapelon, Francoise; Chabbert-Buffet, Nathalie; Teucher, Birgit; Floegel, Anna; Boeing, Heiner; Trichopoulou, Antonia; Adarakis, George; Plada, Maria; Rinaldi, Sabina; Fedirko, Veronika; Romieu, Isabelle; Pala, Valeria; Galasso, Rocco; Sacerdote, Carlotta; Palli, Domenico; Tumino, Rosario; Bueno-de-Mesquita, H. Bas; Gram, Inger Torhild; Gavrilyuk, Oxana; Lund, Eiliv; Sanchez, Maria-Jose; Bonet, Catalina; Chirlaque, Maria-Dolores; Larranaga, Nerea; Barricarte Gurrea, Aurelio; Quiros, Jose R.; Idahl, Annika; Ohlson, Nina; Lundin, Eva; Jirstrom, Karin; Butt, Salma; Tsilidis, Konstantinos K.; Khaw, Kay-Tee; Wareham, Nick; Riboli, Elio; Kaaks, Rudolf; Peeters, Petra H. M.

    2012-01-01

    While the risk of ovarian cancer clearly reduces with each full-term pregnancy, the effect of incomplete pregnancies is unclear. We investigated whether incomplete pregnancies (miscarriages and induced abortions) are associated with risk of epithelial ovarian cancer. This observational study was car

  19. BREAST AND/OR OVARIAN CANCER AS PART OF FAMILY CANCER SYNDROME

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    L. N. Lyubchenko

    2009-01-01

    Full Text Available The problems in the early diagnosis, primary and secondary prevention of family cancer of the breast and/or ovaries are successfully solved within medical genetic counseling at a cancer clinic. Its genetic diagnosis is confirmed, individual risks for breast and/or ovarian cancer are calculated, risk-modifying factors are studied, and treatment, family planning, and childbirth are discussed during clinicogenetic studies.

  20. Identification of ovarian cancer metastatic miRNAs.

    Directory of Open Access Journals (Sweden)

    Souriya Vang

    Full Text Available Serous epithelial ovarian cancer (EOC patients often succumb to aggressive metastatic disease, yet little is known about the behavior and genetics of ovarian cancer metastasis. Here, we aim to understand how omental metastases differ from primary tumors and how these differences may influence chemotherapy. We analyzed the miRNA expression profiles of primary EOC tumors and their respective omental metastases from 9 patients using miRNA Taqman qPCR arrays. We find 17 miRNAs with differential expression in omental lesions compared to primary tumors. miR-21, miR-150, and miR-146a have low expression in most primary tumors with significantly increased expression in omental lesions, with concomitant decreased expression of predicted mRNA targets based on mRNA expression. We find that miR-150 and miR-146a mediate spheroid size. Both miR-146a and miR-150 increase the number of residual surviving cells by 2-4 fold when challenged with lethal cisplatin concentrations. These observations suggest that at least two of the miRNAs, miR-146a and miR-150, up-regulated in omental lesions, stimulate survival and increase drug tolerance. Our observations suggest that cancer cells in omental tumors express key miRNAs differently than primary tumors, and that at least some of these microRNAs may be critical regulators of the emergence of drug resistant disease.

  1. Stem cell-like gene expression in ovarian cancer predicts type II subtype and prognosis.

    Directory of Open Access Journals (Sweden)

    Matthew Schwede

    Full Text Available Although ovarian cancer is often initially chemotherapy-sensitive, the vast majority of tumors eventually relapse and patients die of increasingly aggressive disease. Cancer stem cells are believed to have properties that allow them to survive therapy and may drive recurrent tumor growth. Cancer stem cells or cancer-initiating cells are a rare cell population and difficult to isolate experimentally. Genes that are expressed by stem cells may characterize a subset of less differentiated tumors and aid in prognostic classification of ovarian cancer. The purpose of this study was the genomic identification and characterization of a subtype of ovarian cancer that has stem cell-like gene expression. Using human and mouse gene signatures of embryonic, adult, or cancer stem cells, we performed an unsupervised bipartition class discovery on expression profiles from 145 serous ovarian tumors to identify a stem-like and more differentiated subgroup. Subtypes were reproducible and were further characterized in four independent, heterogeneous ovarian cancer datasets. We identified a stem-like subtype characterized by a 51-gene signature, which is significantly enriched in tumors with properties of Type II ovarian cancer; high grade, serous tumors, and poor survival. Conversely, the differentiated tumors share properties with Type I, including lower grade and mixed histological subtypes. The stem cell-like signature was prognostic within high-stage serous ovarian cancer, classifying a small subset of high-stage tumors with better prognosis, in the differentiated subtype. In multivariate models that adjusted for common clinical factors (including grade, stage, age, the subtype classification was still a significant predictor of relapse. The prognostic stem-like gene signature yields new insights into prognostic differences in ovarian cancer, provides a genomic context for defining Type I/II subtypes, and potential gene targets which following further

  2. An Overview of the Osteopontin as a Diagnostic Marker for Ovarian Cancer%骨桥蛋白与卵巢癌诊断的研究进展

    Institute of Scientific and Technical Information of China (English)

    邹祎

    2011-01-01

    Osteopontin( OPN )is a kind of glyco-phosphoprotein.Immunolocalization of osteopontin showed that the expression levels of OPN in tissue samples from ovarian cancer and borderline ovarian tumors were higher than those from benign tumors and healthy ovarian epithelium.And it is showed that the levels of osteopontin in ovarian cancer of advanced stage were higher than those of early stage.The expression level of the osteopontin is high in lymph node with metastasis of cancer, too.Osteopontin levels in plasma of ovarian cancer were higher than those of benign ovarian disease and the health, which could distinguish the ovarian from the benign ovarian disease and the health.The combination of OPN and other tumor makers improved the diagnostic effects of ovarian cancer significantly.The article summarized the relationship between OPN and some other gynecological diseases.%骨桥蛋白(OPN)是一种磷酸化糖蛋白,不仅在卵巢癌及卵巢交界性恶性肿瘤组织中的表达高于在良性肿瘤和正常卵巢上皮组织,而且晚期卵巢癌组织中的表达也明显高于早期癌,在有癌转移的淋巴结中同样高表达.OPN的血清学检查不仅可以用于区别健康人群和卵巢癌患者,还可用于区分卵巢癌和卵巢良性肿瘤.OPN与其他肿瘤标志物联合检测时可以提高卵巢癌的检出率.本文同时还简述了OPN与其他妇科疾病的关系.

  3. 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.

  4. BRCA1 regulates insulin-like growth factor 1 receptor levels in ovarian cancer

    OpenAIRE

    Liu, Bo; Li, Da; Guan, Yi-Fu

    2014-01-01

    Breast cancer 1 (BRCA1) and insulin-like growth factor 1 receptor (IGF1R) are critical in ovarian cancer progression. However, the crosstalk between the BRCA1 and IGF1R signaling pathways in ovarian cancer remains largely unknown. The effects of BRCA1 on IGF1R were assessed in 121 serous ovarian cancer patients (BRCA1 mutation, n=30; non-BRCA1 mutation, n=32; hypermethylated BRCA1 promoter, n=28; and non-methylation, n=31). BRCA1 promoter methylation was analyzed via bisulfite sequencing usin...

  5. 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...

  6. Serial Patterns of Ovarian Cancer Biomarkers in a Prediagnosis Longitudinal Dataset.

    Science.gov (United States)

    Blyuss, Oleg; Gentry-Maharaj, Alex; Fourkala, Evangelia-Orania; Ryan, Andy; Zaikin, Alexey; Menon, Usha; Jacobs, Ian; Timms, John F

    2015-01-01

    Early detection of ovarian cancer through screening may have impact on mortality from the disease. Approaches based on CA125 cut-off have not been effective. Longitudinal algorithms such as the Risk of Ovarian Cancer Algorithm (ROCA) to interpret CA125 have been shown to have higher sensitivity and specificity than a single cut-off. The aim of this study was to investigate whether other ovarian cancer-related biomarkers, Human Epididymis 4 (HE4), glycodelin, mesothelin, matrix metalloproteinase 7 (MMP7), and cytokeratin 19 fragment (CYFRA 21-1), could improve the performance of CA125 in detecting ovarian cancer earlier. Serum samples (single and serial) predating diagnosis from 47 women taking part in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) who went on to develop primary invasive ovarian, fallopian tube, or peritoneal cancer (index cancer) (170 samples) and 179 matched controls (893 samples) were included in the study. A multiplex immunobased assay platform (Becton Dickinson) allowing simultaneous measurement of the six serum markers was used. The area under the ROC curve for the panel of three biomarkers (CA125, HE4, and glycodelin) was higher than for CA125 alone for all analysed time groups, indicating that these markers can improve on sensitivity of CA125 alone for ovarian cancer detection. PMID:26819954

  7. Serial Patterns of Ovarian Cancer Biomarkers in a Prediagnosis Longitudinal Dataset

    Directory of Open Access Journals (Sweden)

    Oleg Blyuss

    2015-01-01

    Full Text Available Early detection of ovarian cancer through screening may have impact on mortality from the disease. Approaches based on CA125 cut-off have not been effective. Longitudinal algorithms such as the Risk of Ovarian Cancer Algorithm (ROCA to interpret CA125 have been shown to have higher sensitivity and specificity than a single cut-off. The aim of this study was to investigate whether other ovarian cancer-related biomarkers, Human Epididymis 4 (HE4, glycodelin, mesothelin, matrix metalloproteinase 7 (MMP7, and cytokeratin 19 fragment (CYFRA 21-1, could improve the performance of CA125 in detecting ovarian cancer earlier. Serum samples (single and serial predating diagnosis from 47 women taking part in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS who went on to develop primary invasive ovarian, fallopian tube, or peritoneal cancer (index cancer (170 samples and 179 matched controls (893 samples were included in the study. A multiplex immunobased assay platform (Becton Dickinson allowing simultaneous measurement of the six serum markers was used. The area under the ROC curve for the panel of three biomarkers (CA125, HE4, and glycodelin was higher than for CA125 alone for all analysed time groups, indicating that these markers can improve on sensitivity of CA125 alone for ovarian cancer detection.

  8. MicroRNA and transcription factor mediated regulatory network for ovarian cancer: regulatory network of ovarian cancer.

    Science.gov (United States)

    Ying, Huanchun; Lv, Jing; Ying, Tianshu; Li, Jun; Yang, Qing; Ma, Yuan

    2013-10-01

    A better understanding on the regulatory interactions of microRNA (miRNA) target genes and transcription factor (TF) target genes in ovarian cancer may be conducive for developing early diagnosis strategy. Thus, gene expression data and miRNA expression data were downloaded from The Cancer Genome Atlas in this study. Differentially expressed genes and miRNAs were selected out with t test, and Gene Ontology enrichment analysis was performed with DAVID tools. Regulatory interactions were retrieved from miRTarBase, TRED, and TRANSFAC, and then networks for miRNA target genes and TF target genes were constructed to globally present the mechanisms. As a result, a total of 1,939 differentially expressed genes were identified, and they were enriched in 28 functions, among which cell cycle was affected to the most degree. Besides, 213 differentially expressed miRNAs were identified. Two regulatory networks for miRNA target genes and TF target genes were established and then both were combined, in which E2F transcription factor 1, cyclin-dependent kinase inhibitor 1A, cyclin E1, and miR-16 were the hub genes. These genes may be potential biomarkers for ovarian cancer.

  9. 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...

  10. Targeted therapy for hereditary cancer syndromes: hereditary breast and ovarian cancer syndrome, Lynch syndrome, familial adenomatous polyposis, and Li-Fraumeni syndrome.

    Science.gov (United States)

    Agarwal, Rishi; Liebe, Sarah; Turski, Michelle L; Vidwans, Smruti J; Janku, Filip; Garrido-Laguna, Ignacio; Munoz, Javier; Schwab, Richard; Rodon, Jordi; Kurzrock, Razelle; Subbiah, Vivek

    2014-12-01

    Cancer genetics has rapidly evolved in the last two decades. Understanding and exploring the several genetic pathways in the cancer cell is the foundation of targeted therapy. Several genomic aberrations have been identified and their role in carcinogenesis is being explored. In contrast to most cancers where these mutations are acquired, patients with hereditary cancer syndromes have inherited genomic aberrations. The understanding of the molecular pathobiology in hereditary cancer syndromes has advanced dramatically. In addition, many molecularly targeted therapies have been developed that could have potential roles in the treatment of patients with hereditary cancer syndromes. In this review, we outline the presentation, molecular biology, and possible targeted therapies for two of the most widely recognized hereditary cancer syndromes -- hereditary breast and ovarian cancer syndrome and hereditary non-polyposis colorectal cancer syndrome (Lynch syndrome). We will also discuss other syndromes such as familial adenomatous polyposis and Li-Fraumeni syndrome (TP53). PMID:25549704

  11. 全身化疗联合腹腔热灌注化疗并射频热疗治疗晚期卵巢癌%Chemotherapy plus Hyperthermic Intraperitoneal Chemotherapy and Radiofrequency Thermotherapy in the Treatment of Advanced Ovarian Cancer

    Institute of Scientific and Technical Information of China (English)

    杨越; 张蕾; 崔瑶; 杨家梅; 沈叶

    2014-01-01

    Objective To study the efficacy of chemotherapy plus hyperthermic intraperitoneal chemotherapy and radiofrequency thermotherapy in the treatment of advanced ovarian cancer. Methods Sixty patients with advanced ovarian cancer were randomly divided into two groups. Thirty patients of the control group received the chemotherapy plus intraperitoneal chemotherapy,and 30 patients of the observation group received the chemotherapy plus hyper-thermic intraperitoneal chemotherapy and radiofrequency thermotherapy. Results The response rate of the observa-tion group(73. 3%)was higher than that of the control group(40. 0%)(P﹤0. 05). The ascites-control response rate of the observation group(77. 3%)was higher than that of the control group(45. 0%)(P﹤0. 05). There was no significant statistical difference in the toxicities between the two groups(P﹥0. 05). Conclusion Chemotherapy plus hyperthermic intraperitoneal chemotherapy and radiofrequency thermotherapy is effect and safe in the treatment of advanced ovarian cancer.%目的:评价全身化疗联合腹腔热灌注化疗并射频热疗治疗晚期卵巢癌的效果。方法将60例晚期卵巢癌患者随机分为2组,每组30例,对照组30例接受全身化疗联合腹腔灌注化疗,而观察组30例接受全身化疗联合腹腔热灌注化疗并射频热疗。结果观察组有效率为73.3%,高于对照组的40.0%( P﹤0.05);观察组腹水减少有效率为77.3%,高于对照组的45.0%(P﹤0.05)。2组毒副反应相近,且均为轻度。结论全身化疗联合腹腔热灌注化疗并射频热疗治疗晚期卵巢癌的效果治疗晚期卵巢癌安全有效。

  12. Current status and implications of microRNAs in ovarian cancer diagnosis and therapy

    Directory of Open Access Journals (Sweden)

    Zaman Mohd Saif

    2012-12-01

    Full Text Available Abstract Ovarian cancer is the fifth most common cancer among women and causes more deaths than any other type of female reproductive cancer. Currently, treatment of ovarian cancer is based on the combination of surgery and chemotherapy. While recurrent ovarian cancer responds to additional chemotherapy treatments, the progression-free interval becomes shorter after each cycle, as chemo-resistance increases until the disease becomes incurable. There is, therefore, a strong need for prognostic and predictive markers to help optimize and personalize treatment in order to improve the outcome of ovarian cancer. An increasing number of studies indicate an essential role for microRNAs in ovarian cancer progression and chemo-resistance. MicroRNAs (miRNAs are small endogenous non-coding RNAs (~22bp which are frequently dysregulated in cancer. Typically, miRNAs are involved in crucial biological processes, including development, differentiation, apoptosis and proliferation. Two families of miRNAs, miR-200 and let-7, are frequently dysregulated in ovarian cancer and have been associated with poor prognosis. Both have been implicated in the regulation of epithelial-to-mesenchymal transition, a cellular transition associated with tumor aggressiveness, tumor invasion and chemo-resistance. Moreover, miRNAs also have possible implications for improving cancer diagnosis; for example miR-200 family, let-7 family, miR-21 and miR-214 may be useful in diagnostic tests to help detect ovarian cancer at an early stage. Additionally, the use of multiple target O-modified antagomirs (MTG-AMO to inhibit oncogenic miRNAs and miRNA replacement therapy for tumor suppressor miRNAs are essential tools for miRNA based cancer therapeutics. In this review we describe the current status of the role miRNAs play in ovarian cancer and focus on the possibilities of microRNA-based therapies and the use of microRNAs as diagnostic tools.

  13. Transcription factor-microRNA-target gene networks associated with ovarian cancer survival and recurrence.

    Directory of Open Access Journals (Sweden)

    Kristin R Delfino

    Full Text Available The identification of reliable transcriptome biomarkers requires the simultaneous consideration of regulatory and target elements including microRNAs (miRNAs, transcription factors (TFs, and target genes. A novel approach that integrates multivariate survival analysis, feature selection, and regulatory network visualization was used to identify reliable biomarkers of ovarian cancer survival and recurrence. Expression profiles of 799 miRNAs, 17,814 TFs and target genes and cohort clinical records on 272 patients diagnosed with ovarian cancer were simultaneously considered and results were validated on an independent group of 146 patients. Three miRNAs (hsa-miR-16, hsa-miR-22*, and ebv-miR-BHRF1-2* were associated with both ovarian cancer survival and recurrence and 27 miRNAs were associated with either one hazard. Two miRNAs (hsa-miR-521 and hsa-miR-497 were cohort-dependent, while 28 were cohort-independent. This study confirmed 19 miRNAs previously associated with ovarian cancer and identified two miRNAs that have previously been associated with other cancer types. In total, the expression of 838 and 734 target genes and 12 and eight TFs were associated (FDR-adjusted P-value <0.05 with ovarian cancer survival and recurrence, respectively. Functional analysis highlighted the association between cellular and nucleotide metabolic processes and ovarian cancer. The more direct connections and higher centrality of the miRNAs, TFs and target genes in the survival network studied suggest that network-based approaches to prognosticate or predict ovarian cancer survival may be more effective than those for ovarian cancer recurrence. This study demonstrated the feasibility to infer reliable miRNA-TF-target gene networks associated with survival and recurrence of ovarian cancer based on the simultaneous analysis of co-expression profiles and consideration of the clinical characteristics of the patients.

  14. 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.

  15. CHOLINE METABOLISM ALTERATION: A FOCUS ON OVARIAN CANCER

    Directory of Open Access Journals (Sweden)

    Marina eBagnoli

    2016-06-01

    Full Text Available Compared to normal differentiated cells, cancer cells require a metabolic reprogramming to support their high proliferation rates and survival. Aberrant choline metabolism is a fairly new metabolic hallmark reflecting the complex reciprocal interactions between oncogenic signaling and cellular metabolism. Alterations of the involved metabolic network may be sustained by changes in activity of several choline transporters as well as of enzymes like choline kinase-alpha (ChoK-α and phosphatidylcholine-specific phospholipases C and D. Of note, the net outcome of these enzymatic alterations is an increase of phosphocholine and total choline-containing compounds, a cholinic phenotype that can be monitored in cancer by magnetic resonance spectroscopy. This review will highlight the molecular basis for targeting this pathway in epithelial ovarian carcinoma (EOC, a highly heterogeneous and lethal malignancy characterized by late diagnosis, frequent relapse and development of chemoresistance. Modulation of ChoK-α expression impairs only EOC but not normal ovarian cells, thus supporting the hypothesis that cholinic phenotype is a peculiar feature of transformed cells, and indicating ChoK-α targeting as a novel approach to improve efficacy of standard EOC chemotherapeutic treatments.

  16. A case-control study of asthma and ovarian cancer.

    Science.gov (United States)

    Elmasri, Wafic M; Tran, Therese H; Mulla, Zuber D

    2010-01-01

    Epidemiologic studies have found inverse associations between allergy and the development of certain tumors. The authors sought to determine if there was an association between asthma and ovarian cancer. A case-control study was conducted using Florida hospital data (year 2001). Discharge diagnoses were coded using the ICD-9-CM (International Classification of Diseases, Ninth Revision, Clinical Modification). Cases were 1,582 women whose principal discharge diagnosis was a malignant neoplasm of the ovary. Two control series were used: 4,744 women whose principal diagnosis was an upper limb bone fracture, and 21,830 women whose principal diagnosis was an acute myocardial infarction. Odds ratios (ORs) adjusted for age, race-ethnicity, Medicaid status, obesity, and smoking were calculated. Cases were 30% less likely than fracture control to be asthmatics (adjusted OR = 0.70, 95% confidence interval [CI]: 0.49-0.99, p = .04). Similarly, cases when compared to acute myocardial infarction controls were significantly less likely to have asthma (adjusted OR = 0.62, 95% CI: 0.45-0.87, p = .005). The results of this statewide exploratory study suggest that individuals with asthma may have a lower risk of developing ovarian cancer than nonasthmatics. PMID:20439229

  17. Low-dose aspirin use and the risk of ovarian cancer in Denmark

    DEFF Research Database (Denmark)

    Baandrup, Lone; Kjaer, S K; Olsen, J H;

    2015-01-01

    BACKGROUND: A comprehensive body of evidence has shown that aspirin has cancer-preventive effects, particularly against gastrointestinal cancer, but its effects on the risk of ovarian cancer are less well established. This nationwide case-control study examined the association between low...... were seen for mucinous and endometrioid tumours. CONCLUSION: This nationwide case-control study indicates that low-dose aspirin use may be associated with a reduced risk of epithelial ovarian cancer....... regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for the association between low-dose aspirin use and the risk of epithelial ovarian cancer, both overall and for specific histological types. RESULTS: For 4103 ovarian cancer cases and 58 706 population controls, the...

  18. The Prevention of Hereditary Breast and Ovarian Cancer: A Personal View

    Directory of Open Access Journals (Sweden)

    Narod Steven

    2004-02-01

    Full Text Available Abstract Options for the prevention of hereditary breast and ovarian cancer include screening, preventive surgery and chemoprevention. Screening studies with magnetic resonance imaging of the breast are promising but the technology is not widespread and MRI is unlikely to be available as a screening tool in the near future. Prophylactic oophorectomy and mastectomy are effective preventive measures and are gaining in acceptance by patients and physicians. Preventive mastectomy is effective against both primary and contralateral breast cancer. Oophorectomy prevents ovarian cancer, and if done prior to menopause, will prevent breast cancer as well. Tamoxifen has been shown to prevent contralateral breast cancers in BRCA1 and BRCA2 carriers but is not widely accepted as a means of primary prevention. Oral contraceptives and tubal ligation will reduce the risk of hereditary ovarian cancer and should be considered in women who wish to retain ovarian function.

  19. Potent cytotoxic effects of Calomeria amaranthoides on ovarian cancers

    Directory of Open Access Journals (Sweden)

    van Haard Paul MM

    2011-03-01

    Full Text Available Abstract Background Ovarian cancer remains the leading cause of death from gynaecological malignancy. More than 60% of the patients are presenting the disease in stage III or IV. In spite of combination of chemotherapy and surgery the prognosis stays poor for therapy regimen. Methods The leaves of a plant endemic to Australia, Calomeria amaranthoides, were extracted and then fractionated by column chromatography. In vitro cytotoxicity tests were performed with fractions of the plant extract and later with an isolated compound on ovarian cancer cell lines, as well as normal fibroblasts at concentrations of 1-100 μg/mL (crude extract and 1-10 μg/mL (compound. Cytotoxicity was measured after 24, 48 and 72 hours by using a non-fluorescent substrate, Alamar blue. In vivo cytotoxicity was tested on ascites, developed in the abdomen of nude mice after inoculation with human OVCAR3 cells intraperitoneally. The rate of change in abdomen size for the mice was determined by linear regression and statistically evaluated for significance by the unpaired t test. Results Two compounds were isolated by chromatographic fractionation and identified by 1H-NMR, 13C-NMR and mass spectrometry analyses, EPD, an α-methylene sesquiterpene lactone of the eremophilanolide subtype, and EPA, an α-methylene carboxylic acid. Cytotoxicity of EPD for normal fibroblasts at all time points IC50 was greater than 10 μg/mL, whereas, for OVCAR3 cells at 48 hours IC50 was 5.3 μg/mL (95% confidence interval 4.3 to 6.5 μg/mL. Both, the crude plant extract as well as EPD killed the cancer cells at a final concentration of 10 μg/mL and 5 μg/mL respectively, while in normal cells only 20% cell killing effect was observed. EPA had no cytotoxic effects. Changes in abdomen size for control versus Cisplatin treated mice were significantly different, P = 0.023, as were control versus EPD treated mice, P = 0.025, whereas, EPD versus Cisplatin treated mice were not significantly

  20. Intrafamilial disclosure of risk for hereditary breast and ovarian cancer: points to consider.

    Science.gov (United States)

    Black, Lee; McClellan, Kelly A; Avard, Denise; Knoppers, Bartha Maria

    2013-04-01

    The primary goal of breast and ovarian cancer screening is to minimize the cases of advanced disease and therefore its mortality rate. For hereditary breast and ovarian cancer, one method to reach this goal is to disseminate genetic risk information among family members. However, experience tells us that this information does not always reach family members in a timely manner, if at all. There are many moving parts to a decision to disclose genetic risk information within a family, and the lack of detail and cohesion in current guidelines do a disservice to hereditary breast cancer prevention. Utilizing legal, medical, and policy databases for literature, case law and policy documents relating to communication of genetic test results within families, as well as a consultative process with representative stakeholders, a points to consider has been developed to address a number of issues that might impact the ability and willingness of patients to inform family members of genetic risk. These include: what is "genetic information"; who is the "family"; why should patients inform their family members; and how should health professionals be involved in this process? This represents only an initial step towards fostering better communication within families. Additional research is needed to determine the best methods for encouraging this communication and motivations for disclosing or not and to promote the development of a solution, considering the complexity of human relationships and the probabilistic nature of genetic information. PMID:23275181

  1. 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.

  2. Gene expression profiling supports the hypothesis that human ovarian surface epithelia are multipotent and capable of serving as ovarian cancer initiating cells

    Directory of Open Access Journals (Sweden)

    Matyunina Lilya V

    2009-12-01

    Full Text Available Abstract Background Accumulating evidence suggests that somatic stem cells undergo mutagenic transformation into cancer initiating cells. The serous subtype of ovarian adenocarcinoma in humans has been hypothesized to arise from at least two possible classes of progenitor cells: the ovarian surface epithelia (OSE and/or an as yet undefined class of progenitor cells residing in the distal end of the fallopian tube. Methods Comparative gene expression profiling analyses were carried out on OSE removed from the surface of normal human ovaries and ovarian cancer epithelial cells (CEPI isolated by laser capture micro-dissection (LCM from human serous papillary ovarian adenocarcinomas. The results of the gene expression analyses were randomly confirmed in paraffin embedded tissues from ovarian adenocarcinoma of serous subtype and non-neoplastic ovarian tissues using immunohistochemistry. Differentially expressed genes were analyzed using gene ontology, molecular pathway, and gene set enrichment analysis algorithms. Results Consistent with multipotent capacity, genes in pathways previously associated with adult stem cell maintenance are highly expressed in ovarian surface epithelia and are not expressed or expressed at very low levels in serous ovarian adenocarcinoma. Among the over 2000 genes that are significantly differentially expressed, a number of pathways and novel pathway interactions are identified that may contribute to ovarian adenocarcinoma development. Conclusions Our results are consistent with the hypothesis that human ovarian surface epithelia are multipotent and capable of serving as the origin of ovarian adenocarcinoma. While our findings do not rule out the possibility that ovarian cancers may also arise from other sources, they are inconsistent with claims that ovarian surface epithelia cannot serve as the origin of ovarian cancer initiating cells.

  3. Cryopreservation of ovarian tissue for fertility preservation: no evidence of malignant cell contamination in ovarian tissue from patients with breast cancer

    DEFF Research Database (Denmark)

    Rosendahl, Mikkel; Timmermans Wielenga, Vera; Nedergaard, Lotte;

    2011-01-01

    Cryopreserved ovarian cortical biopsies from 51 patients with breast cancer were examined by histologic and immunohistochemical analysis and showed no sign of metastases. Autotransplantation of ovarian cortex to patients with low-stage breast cancer disease appears safe, but confirmatory studies...

  4. Exosomes: Emerging biomarkers and targets for ovarian cancer.

    Science.gov (United States)

    Tang, Maggie K S; Wong, Alice S T

    2015-10-10

    The limitations of current chemotherapies have motivated research in developing new treatments. Growing evidence shows that interaction between tumors and their microenvironment, but not tumor cells per se, is the key factor in tumor progression and therefore of obvious scientific interest and therapeutic value. Exosomes are small (30-100 nm) extracellular vesicles which have emerged as key mediators of intercellular communication between tumor cells and major cell types in the tumor microenvironment such as fibroblasts, endothelial cells, and immune cells as well as noncellular extracellular matrices through paracrine mechanisms. This review is to highlight the emerging role of exosomes in particular types of cancer, such as ovarian cancer, owing to its unique route of metastasis, which is capable of rapidly translating exosome research for clinical applications in diagnosis, prognosis, and potential treatment.

  5. Will Chinese ovarian cancer patients benefit from knowing the BRCA2 mutation status?

    OpenAIRE

    Liu, Guo-Yan; Zhang, Wei

    2012-01-01

    In Western countries, the mutation status of the BRCA1 and BRCA2 genes is commonly determined for genetic counseling among members of families with a history of breast or ovarian cancer, especially for women of the Ashkenazi Jewish ethnicity. Recent studies in the Cancer Genome Atlas project have demonstrated that BRCA2 mutation carriers are more responsive to platinum-based chemotherapy among high-grade serous ovarian cancer patients. Thus, in Western countries, the mutation status of BRCA1 ...

  6. An epidemiologic risk prediction model for ovarian cancer in Europe : The EPIC study

    OpenAIRE

    Li, K; Huesing, A.; Fortner, R. T.; Tjonneland, A.; Hansen, L.; Dossus, L; Chang-Claude, J; Bergmann, M.; A. Steffen; Bamia, C.; Trichopoulos, D; Trichopoulou, A; Palli, D; Mattiello, A; Agnoli, C

    2015-01-01

    Background: Ovarian cancer has a high case-fatality ratio, largely due to late diagnosis. Epidemiologic risk prediction models could help identify women at increased risk who may benefit from targeted prevention measures, such as screening or chemopreventive agents. Methods: We built an ovarian cancer risk prediction model with epidemiologic risk factors from 202 206 women in the European Prospective Investigation into Cancer and Nutrition study. Results: Older age at menopause, longer durati...

  7. Paclitaxel sensitivity in relation to ABCB1 expression, efflux and single nucleotide polymorphisms in ovarian cancer

    OpenAIRE

    Gao, Bo; Russell, Amanda; Beesley, Jonathan; Chen, Xiao Qing; Healey, Sue; Henderson, Michelle; Wong, Mark; Emmanuel, Catherine; Johnatty, Sharon E.; ,; Bowtell, David; Gertig, Dorota; Green, Adle; Webb, Penelope; Hung, Jillian

    2014-01-01

    ABCB1 (adenosine triphosphate-binding cassette transporter B1) mediates cellular elimination of many chemotherapeutic agents including paclitaxel, which is commonly used to treat ovarian cancer. A significant association between common single nucleotide polymorphisms (SNPs) in ABCB1 and progression-free survival has been reported in patients with ovarian cancer. Variable paclitaxel clearance due to genotype specific differences in ABCB1 activity in cancer cells and/or normal tissues may under...

  8. 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...

  9. Bruton's tyrosine kinase (Btk) inhibitor ibrutinib suppresses stem-like traits in ovarian cancer

    OpenAIRE

    Zucha, Muhammad Ary; Wu, Alexander T. H.; Lee, Wei-Hwa; Wang, Liang-Shun; Lin, Wan-Wan; Yuan, Chiou-Chung; Yeh, Chi-Tai

    2015-01-01

    According to a Prognoscan database, upregulation of Bruton's tyrosine kinase (Btk) is associated with low overall survival in ovarian cancer patients. We found that spheroids-forming ovarian cancer cell, which highly expressed cancer stem-like cell (CSC) markers and Btk, were cisplatin resistant. We next treated CSCs and non-CSCs by a combination of ibrutinib and cisplatin. We found that chemoresistance was dependent on Btk and JAK2/STAT3, which maintained CSC by inducing Sox-2 and prosurviva...

  10. 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

  11. A non-synonymous polymorphism in IRS1 modifies risk of developing breast and ovarian cancers in BRCA1 and ovarian cancer in BRCA2 mutation carriers

    Science.gov (United States)

    Ding, Yuan C.; McGuffog, Lesley; Healey, Sue; Friedman, Eitan; Laitman, Yael; Shani-Shimon–Paluch; Kaufman, Bella; Liljegren, Annelie; Lindblom, Annika; Olsson, Håkan; Kristoffersson, Ulf; Stenmark-Askmalm, Marie; Melin, Beatrice; Domchek, Susan M.; Nathanson, Katherine L.; Rebbeck, Timothy R.; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Gronwald, Jacek; Huzarski, Tomasz; Cybulski, Cezary; Byrski, Tomasz; Osorio, Ana; Cajal, Teresa Ramóny; Stavropoulou, Alexandra V; Benítez, Javier; Hamann, Ute; Rookus, Matti; Aalfs, Cora M.; de Lange, Judith L.; Meijers-Heijboer, Hanne E.J.; Oosterwijk, Jan C.; van Asperen, Christi J.; García, Encarna B. Gómez; Hoogerbrugge, Nicoline; Jager, Agnes; van der Luijt, Rob B.; Easton, Douglas F.; Peock, Susan; Frost, Debra; Ellis, Steve D.; Platte, Radka; Fineberg, Elena; Evans, D. Gareth; Lalloo, Fiona; Izatt, Louise; Eeles, Ros; Adlard, Julian; Davidson, Rosemarie; Eccles, Diana; Cole, Trevor; Cook, Jackie; Brewer, Carole; Tischkowitz, Marc; Godwin, Andrew K.; Pathak, Harsh; Stoppa-Lyonnet, Dominique; Sinilnikova, Olga M.; Mazoyer, Sylvie; Barjhoux, Laure; Léoné, Mélanie; Gauthier-Villars, Marion; Caux-Moncoutier, Virginie; de Pauw, Antoine; Hardouin, Agnès; Berthet, Pascaline; Dreyfus, Hélène; Ferrer, Sandra Fert; Collonge-Rame, Marie-Agnès; Sokolowska, Johanna; Buys, Saundra; Daly, Mary; Miron, Alex; Terry, Mary Beth; Chung, Wendy; John, Esther M; Southey, Melissa; Goldgar, David; Singer, Christian F; Maria, Muy-Kheng Tea; Gschwantler-Kaulich, Daphne; Fink-Retter, Anneliese; Hansen, Thomas v. O.; Ejlertsen, Bent; Johannsson, Oskar Th.; Offit, Kenneth; Sarrel, Kara; Gaudet, Mia M.; Vijai, Joseph; Robson, Mark; Piedmonte, Marion R; Andrews, Lesley; Cohn, David; DeMars, Leslie R.; DiSilvestro, Paul; Rodriguez, Gustavo; Toland, Amanda Ewart; Montagna, Marco; Agata, Simona; Imyanitov, Evgeny; Isaacs, Claudine; Janavicius, Ramunas; Lazaro, Conxi; Blanco, Ignacio; Ramus, Susan J; Sucheston, Lara; Karlan, Beth Y.; Gross, Jenny; Ganz, Patricia A.; Beattie, Mary S.; Schmutzler, Rita K.; Wappenschmidt, Barbara; Meindl, Alfons; Arnold, Norbert; Niederacher, Dieter; Preisler-Adams, Sabine; Gadzicki, Dorotehea; Varon-Mateeva, Raymonda; Deissler, Helmut; Gehrig, Andrea; Sutter, Christian; Kast, Karin; Nevanlinna, Heli; Aittomäki, Kristiina; Simard, Jacques; Spurdle, Amanda B.; Beesley, Jonathan; Chen, Xiaoqing; Tomlinson, Gail E.; Weitzel, Jeffrey; Garber, Judy E.; Olopade, Olufunmilayo I.; Rubinstein, Wendy S.; Tung, Nadine; Blum, Joanne L.; Narod, Steven A.; Brummel, Sean; Gillen, Daniel L.; Lindor, Noralane; Fredericksen, Zachary; Pankratz, Vernon S.; Couch, Fergus J.; Radice, Paolo; Peterlongo, Paolo; Greene, Mark H.; Loud, Jennifer T.; Mai, Phuong L.; Andrulis, Irene L.; Glendon, Gord; Ozcelik, Hilmi; Gerdes, Anne-Marie; Thomassen, Mads; Jensen, Uffe Birk; Skytte, Anne-Bine; Caligo, Maria A.; Lee, Andrew; Chenevix-Trench, Georgia; Antoniou, Antonis C; Neuhausen, Susan L.

    2012-01-01

    Background We previously reported significant associations between genetic variants in insulin receptor substrate 1 (IRS1) and breast cancer risk in women carrying BRCA1 mutations. The objectives of this study were to investigate whether the IRS1 variants modified ovarian cancer risk and were associated with breast cancer risk in a larger cohort of BRCA1 and BRCA2 mutation carriers. Methods IRS1 rs1801123, rs1330645, and rs1801278 were genotyped in samples from 36 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Data were analyzed by a retrospective cohort approach modeling the associations with breast and ovarian cancer risks simultaneously. Analyses were stratified by BRCA1 and BRCA2 status and mutation class in BRCA1 carriers. Results Rs1801278 (Gly972Arg) was associated with ovarian cancer risk for both BRCA1 [Hazard ratio (HR) = 1.43; 95% CI: 1.06–1.92; p = 0.019] and BRCA2 mutation carriers (HR=2.21; 95% CI: 1.39–3.52, p=0.0008). For BRCA1 mutation carriers, the breast cancer risk was higher in carriers with class 2 mutations than class 1 (mutations (class 2 HR=1.86, 95% CI: 1.28–2.70; class 1 HR=0.86, 95%CI:0.69–1.09; p-for difference=0.0006). Rs13306465 was associated with ovarian cancer risk in BRCA1 class 2 mutation carriers (HR = 2.42; p = 0.03). Conclusion The IRS1 Gly972Arg SNP, which affects insulin-like growth factor and insulin signaling, modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers and breast cancer risk in BRCA1 class 2 mutation carriers. Impact These findings may prove useful for risk prediction for breast and ovarian cancers in BRCA1 and BRCA2 mutation carriers. PMID:22729394

  12. Human omental-derived adipose stem cells increase ovarian cancer proliferation, migration, and chemoresistance.

    Directory of Open Access Journals (Sweden)

    Aleksandra Nowicka

    Full Text Available Adipose tissue contains a population of multipotent adipose stem cells (ASCs that form tumor stroma and can promote tumor progression. Given the high rate of ovarian cancer metastasis to the omental adipose, we hypothesized that omental-derived ASC may contribute to ovarian cancer growth and dissemination.We isolated ASCs from the omentum of three patients with ovarian cancer, with (O-ASC4, O-ASC5 and without (O-ASC1 omental metastasis. BM-MSCs, SQ-ASCs, O-ASCs were characterized with gene expression arrays and metabolic analysis. Stromal cells effects on ovarian cancer cells proliferation, chemoresistance and radiation resistance was evaluated using co-culture assays with luciferase-labeled human ovarian cancer cell lines. Transwell migration assays were performed with conditioned media from O-ASCs and control cell lines. SKOV3 cells were intraperitionally injected with or without O-ASC1 to track in-vivo engraftment.O-ASCs significantly promoted in vitro proliferation, migration chemotherapy and radiation response of ovarian cancer cell lines. O-ASC4 had more marked effects on migration and chemotherapy response on OVCA 429 and OVCA 433 cells than O-ASC1. Analysis of microarray data revealed that O-ASC4 and O-ASC5 have similar gene expression profiles, in contrast to O-ASC1, which was more similar to BM-MSCs and subcutaneous ASCs in hierarchical clustering. Human O-ASCs were detected in the stroma of human ovarian cancer murine xenografts but not uninvolved ovaries.ASCs derived from the human omentum can promote ovarian cancer proliferation, migration, chemoresistance and radiation resistance in-vitro. Furthermore, clinical O-ASCs isolates demonstrate heterogenous effects on ovarian cancer in-vitro.

  13. 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...

  14. Identifying microRNA/mRNA dysregulations in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Miles Gregory D

    2012-03-01

    Full Text Available Abstract Background MicroRNAs are a class of noncoding RNA molecules that co-regulate the expression of multiple genes via mRNA transcript degradation or translation inhibition. Since they often target entire pathways, they may be better drug targets than genes or proteins. MicroRNAs are known to be dysregulated in many tumours and associated with aggressive or poor prognosis phenotypes. Since they regulate mRNA in a tissue specific manner, their functional mRNA targets are poorly understood. In previous work, we developed a method to identify direct mRNA targets of microRNA using patient matched microRNA/mRNA expression data using an anti-correlation signature. This method, applied to clear cell Renal Cell Carcinoma (ccRCC, revealed many new regulatory pathways compromised in ccRCC. In the present paper, we apply this method to identify dysregulated microRNA/mRNA mechanisms in ovarian cancer using data from The Cancer Genome Atlas (TCGA. Methods TCGA Microarray data was normalized and samples whose class labels (tumour or normal were ambiguous with respect to consensus ensemble K-Means clustering were removed. Significantly anti-correlated and correlated genes/microRNA differentially expressed between tumour and normal samples were identified. TargetScan was used to identify gene targets of microRNA. Results We identified novel microRNA/mRNA mechanisms in ovarian cancer. For example, the expression level of RAD51AP1 was found to be strongly anti-correlated with the expression of hsa-miR-140-3p, which was significantly down-regulated in the tumour samples. The anti-correlation signature was present separately in the tumour and normal samples, suggesting a direct causal dysregulation of RAD51AP1 by hsa-miR-140-3p in the ovary. Other pairs of potentially biological relevance include: hsa-miR-145/E2F3, hsa-miR-139-5p/TOP2A, and hsa-miR-133a/GCLC. We also identified sets of positively correlated microRNA/mRNA pairs that are most likely result from

  15. 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...

  16. Prognostic Impact of ABO Blood Group on the Survival in Patients with Ovarian Cancer

    OpenAIRE

    Zhou, Juan; Yang, Li-Chao; He, Zhen-Yu; Li, Fang-Yan; Wu, San-Gang; Sun, Jia-yuan

    2015-01-01

    Purpose: The impact of ABO blood group on the survival of patients with ovarian cancer remains uncertain. The aim of this study was to evaluate the prognostic value of the ABO blood group in ovarian cancer patients. Methods: 256 ovarian cancer patients who received a cytoreductive surgery were retrospectively reviewed. The prognostic impact of the ABO blood group with respect to overall survival (OS) was analyzed. Results: The median follow-up time was 57 months and the 5-year OS was 70.1%. T...

  17. Prescription Use of Paracetamol and Risk for Ovarian Cancer in Denmark

    DEFF Research Database (Denmark)

    Baandrup, Louise; Friis, Søren; Dehlendorff, Christian;

    2014-01-01

    % confidence intervals (CIs) for ovarian cancer associated with use of paracetamol or nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs). All statistical tests were two-sided. Use of paracetamol was associated with a reduced odds ratio for ovarian cancer (OR = 0.82; 95% CI = 0.74 to 0.92; P ...) compared with nonuse, and the odds ratio decreased further with long-term (≥10 years), high-intensity paracetamol use (OR = 0.45; 95% CI = 0.24 to 0.86; P = .02). Use of nonaspirin NSAIDs was not associated with ovarian cancer risk....

  18. Spatial and Temporal Heterogeneity in High-Grade Serous Ovarian Cancer: A Phylogenetic Analysis

    OpenAIRE

    Roland F Schwarz; Ng, Charlotte K.Y.; Cooke, Susanna L.; Scott Newman; Jillian Temple; Piskorz, Anna M.; Davina Gale; Karen Sayal; Muhammed Murtaza; Baldwin, Peter J.; Nitzan Rosenfeld; Earl, Helena M.; Evis Sala; Mercedes Jimenez-Linan; Parkinson, Christine A.

    2015-01-01

    Editors’ Summary Background Every year, nearly 250,000 women develop ovarian cancer, and about 150,000 die from the disease. Ovarian cancer occurs when a cell on the surface of the ovaries (two small organs in the pelvis that produce eggs) or in the Fallopian tubes (which connect the ovaries to the womb) acquires genetic changes (mutations) that allow it to grow uncontrollably and to spread around the body (metastasize). For women whose ovarian cancer is diagnosed when it is confined to its s...

  19. Immune Checkpoint Inhibitors: A New Opportunity in the Treatment of Ovarian Cancer?

    Directory of Open Access Journals (Sweden)

    Gloria Mittica

    2016-07-01

    Full Text Available Epithelial ovarian cancer (EOC is the leading cause of death for gynecological cancer. The standard treatment for advanced stage is the combination of optimal debulking surgery and platinum-based chemotherapy. Nevertheless, recurrence is frequent (around 70% and prognosis is globally poor. New therapeutic agents are needed to improve survival. Since EOC is strongly immunogenic, immune checkpoint inhibitors are under evaluation for their capacity to contrast the “turn off” signals expressed by the tumor to escape the immune system and usually responsible for self-tolerance maintenance. This article reviews the literature on anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4, anti-PD-1, anti-PD-L1, and anti-PD-L2 antibodies in EOC and highlights their possible lines of development. Further studies are needed to better define the prognostic role of the immune checkpoint inhibitors, to identify predictors of response and the optimal clinical setting in EOC.

  20. Immune Checkpoint Inhibitors: A New Opportunity in the Treatment of Ovarian Cancer?

    Science.gov (United States)

    Mittica, Gloria; Genta, Sofia; Aglietta, Massimo; Valabrega, Giorgio

    2016-01-01

    Epithelial ovarian cancer (EOC) is the leading cause of death for gynecological cancer. The standard treatment for advanced stage is the combination of optimal debulking surgery and platinum-based chemotherapy. Nevertheless, recurrence is frequent (around 70%) and prognosis is globally poor. New therapeutic agents are needed to improve survival. Since EOC is strongly immunogenic, immune checkpoint inhibitors are under evaluation for their capacity to contrast the "turn off" signals expressed by the tumor to escape the immune system and usually responsible for self-tolerance maintenance. This article reviews the literature on anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), anti-PD-1, anti-PD-L1, and anti-PD-L2 antibodies in EOC and highlights their possible lines of development. Further studies are needed to better define the prognostic role of the immune checkpoint inhibitors, to identify predictors of response and the optimal clinical setting in EOC. PMID:27447625

  1. Prediction of response to chemotherapy by ERCC1 immunohistochemistry and ERCC1 polymorphism in ovarian cancer

    DEFF Research Database (Denmark)

    Dahl Steffensen, Karina; Waldstrøm, M.; Jeppesen, Ulla;

    2007-01-01

    The response of tumor cells to platinum-based chemotherapy involves DNA repair mechanisms. Excision repair cross-complementation group 1 (ercc1) is one of the leading genes involved in DNA repair, and several studies have linked ercc1 to platinum resistance in cell lines and in human cancers....... A common single nucleotide polymorphism (SNP) of ercc1 at codon 118 has been proposed to impair ercc1 translation and reduce ERCC1 protein expression and consequently influence the response to platinum-based chemotherapy. The primary aim of the present study was to evaluate ERCC1 expression and ercc1 codon...... 118 polymorphism in epithelial ovarian cancer (EOC) and their possible predictive value in patients treated with platinum-based chemotherapy. Formalin-fixed, paraffin-embedded tissue sections from 159 patients with advanced EOC were used for immunohistochemistry. Ercc1 codon 118 SNP genotyping...

  2. 理冲汤加减方联合化疗治疗晚期卵巢癌的临床研究%Clinical Research on Effect of Changed Lichong Decoction Combined Chemotherapy in The Treatment of Advanced Ovarian Cancer

    Institute of Scientific and Technical Information of China (English)

    裴霞; 杜业勤; 刘开江

    2011-01-01

    目的:评价中药理冲汤加减方联合化疗治疗晚期卵巢癌的临床疗效.方法:将70例卵巢癌患者随机分为两组,治疗组(35例)于化疗第2天服用理冲汤加减方,水煎服每日1剂,至下1周期化疗开始,共20天;对照组(35例)单独使用化疗药物,化疗结束后不再用药.观察化疗药物消化道不良反应、患者生活质量、血液流变、血小板膜糖蛋白在治疗前后的变化,评价疗效.结果:两组治疗后与治疗前比较,血液流变高、中、低切值、血浆黏度、消化道反应、生活质量、CD62P表达,差异均有显著性(P<0.05);两组治疗后比较,血流变中、低切值、血浆黏度、消化道反应、生活质量、CD62P表达,差异均有显著性(P<0.05).结论:理冲汤加减方联合化疗对晚期卵巢癌的治疗在减轻消化道反应方面疗效显著,可使患者血栓前状态得以改善,可能对减少卵巢癌病变复发转移有意义.%Objective:To evaluate the clinical efficacy of changed Lichong decoction plus chemotherapy for advanced ovarian carcinoma.Methods:70 advanced ovarian carcinoma patients were randomly divided into two groups:treatment group in which 35 patients were treated with chemotherapy plus changed Lichong decoction and control group treated with simple chemotherapy.The digestive tract reactions of chemotherapy,quality of life, blood flow and platelet membranous glycopretein were observed before and after treatment.Results: The levels of blood flow、 blood plasma, digestive reactions, quality of life as well as the expression of CD62P after treatment were significantly changed in beth groups with significant difference as compared with those before treatment ( both P < 0.05 ); And comparison between the two groups in the levels of blood flow, blood plasma, digestive reactions, quality of life as well as the expression of CD62P aftertreatment also showed significant difference ( P < 0.05 ).Conclusion: Lichong decoction plus

  3. Ovarian Cancer: Can Proteomics Give New Insights for Therapy and Diagnosis?

    Directory of Open Access Journals (Sweden)

    Massimo Federico

    2013-04-01

    Full Text Available The study of the ovarian proteomic profile represents a new frontier in ovarian cancer research, since this approach is able to enlighten the wide variety of post-translational events (such as glycosylation and phosphorylation. Due to the possibility of analyzing thousands of proteins, which could be simultaneously altered, comparative proteomics represent a promising model of possible biomarker discovery for ovarian cancer detection and monitoring. Moreover, defining signaling pathways in ovarian cancer cells through proteomic analysis offers the opportunity to design novel drugs and to optimize the use of molecularly targeted agents against crucial and biologically active pathways. Proteomic techniques provide more information about different histological types of ovarian cancer, cell growth and progression, genes related to tumor microenvironment and specific molecular targets predictive of response to chemotherapy than sequencing or microarrays. Estimates of specificity with proteomics are less consistent, but suggest a new role for combinations of biomarkers in early ovarian cancer diagnosis, such as the OVA1 test. Finally, the definition of the proteomic profiles in ovarian cancer would be accurate and effective in identifying which pathways are differentially altered, defining the most effective therapeutic regimen and eventually improving health outcomes.

  4. 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.

  5. An epidemiologic risk prediction model for ovarian cancer in Europe : The EPIC study

    NARCIS (Netherlands)

    Li, K.; Huesing, A.; Fortner, R. T.; Tjonneland, A.; Hansen, L.; Dossus, L.; Chang-Claude, J.; Bergmann, M.; Steffen, A.; Bamia, C.; Trichopoulos, D.; Trichopoulou, A.; Palli, D.; Mattiello, A.; Agnoli, C.; Tumino, R.; Onland-Moret, N. C.; Peeters, P. H.; Bueno-de-Mesquita, H. B(as); Gram, I. T.; Weiderpass, E.; Sanchez-Cantalejo, E.; Chirlaque, M-D; Duell, E. J.; Ardanaz, E.; Idahl, A.; Lundin, E.; Khaw, K-T; Travis, R. C.; Merritt, M. A.; Gunter, M. J.; Riboli, E.; Ferrari, P.; Terry, K.; Cramer, D.; Kaaks, R.

    2015-01-01

    Background: Ovarian cancer has a high case-fatality ratio, largely due to late diagnosis. Epidemiologic risk prediction models could help identify women at increased risk who may benefit from targeted prevention measures, such as screening or chemopreventive agents. Methods: We built an ovarian canc

  6. The TGFβ pathway stimulates ovarian cancer cell proliferation by increasing IGF1R levels.

    Science.gov (United States)

    Alsina-Sanchis, Elisenda; Figueras, Agnès; Lahiguera, Álvaro; Vidal, August; Casanovas, Oriol; Graupera, Mariona; Villanueva, Alberto; Viñals, Francesc

    2016-10-15

    In a search for new therapeutic targets for treating epithelial ovarian cancer, we analyzed the Transforming Growth Factor Beta (TGFβ) signaling pathway in these tumors. Using a TMA with patient samples we found high Smad2 phosphorylation in ovarian cancer tumoral cells, independently of tumor subtype (high-grade serous or endometrioid). To evaluate the impact of TGFβ receptor inhibition on tumoral growth, we used different models of human ovarian cancer orthotopically grown in nude mice (OVAs). Treatment with a TGFβRI&II dual inhibitor, LY2109761, caused a significant reduction in tumor size in all these models, affecting cell proliferation rate. We identified Insulin Growth Factor (IGF)1 receptor as the signal positively regulated by TGFβ implicated in ovarian tumor cell proliferation. Inhibition of IGF1R activity by treatment with a blocker antibody (IMC-A12) or with a tyrosine kinase inhibitor (linsitinib) inhibited ovarian tumoral growth in vivo. When IGF1R levels were decreased by shRNA treatment, LY2109761 lost its capacity to block tumoral ovarian cell proliferation. At the molecular level TGFβ induced mRNA IGF1R levels. Overall, our results suggest an important role for the TGFβ signaling pathway in ovarian tumor cell growth through the control of IGF1R signaling pathway. Moreover, it identifies anti-TGFβ inhibitors as being of potential use in new therapies for ovarian cancer patients as an alternative to IGF1R inhibition. PMID:27299695

  7. The TGFβ pathway stimulates ovarian cancer cell proliferation by increasing IGF1R levels.

    Science.gov (United States)

    Alsina-Sanchis, Elisenda; Figueras, Agnès; Lahiguera, Álvaro; Vidal, August; Casanovas, Oriol; Graupera, Mariona; Villanueva, Alberto; Viñals, Francesc

    2016-10-15

    In a search for new therapeutic targets for treating epithelial ovarian cancer, we analyzed the Transforming Growth Factor Beta (TGFβ) signaling pathway in these tumors. Using a TMA with patient samples we found high Smad2 phosphorylation in ovarian cancer tumoral cells, independently of tumor subtype (high-grade serous or endometrioid). To evaluate the impact of TGFβ receptor inhibition on tumoral growth, we used different models of human ovarian cancer orthotopically grown in nude mice (OVAs). Treatment with a TGFβRI&II dual inhibitor, LY2109761, caused a significant reduction in tumor size in all these models, affecting cell proliferation rate. We identified Insulin Growth Factor (IGF)1 receptor as the signal positively regulated by TGFβ implicated in ovarian tumor cell proliferation. Inhibition of IGF1R activity by treatment with a blocker antibody (IMC-A12) or with a tyrosine kinase inhibitor (linsitinib) inhibited ovarian tumoral growth in vivo. When IGF1R levels were decreased by shRNA treatment, LY2109761 lost its capacity to block tumoral ovarian cell proliferation. At the molecular level TGFβ induced mRNA IGF1R levels. Overall, our results suggest an important role for the TGFβ signaling pathway in ovarian tumor cell growth through the control of IGF1R signaling pathway. Moreover, it identifies anti-TGFβ inhibitors as being of potential use in new therapies for ovarian cancer patients as an alternative to IGF1R inhibition.

  8. TNF-α expression, risk factors, and inflammatory exposures in ovarian cancer: evidence for an inflammatory pathway of ovarian carcinogenesis?

    Science.gov (United States)

    Gupta, Mamta; Babic, Ana; Beck, Andrew H; Terry, Kathryn

    2016-08-01

    Inflammatory cytokines, like tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), are elevated in ovarian cancer. Differences in cytokine expression by histologic subytpe or ovarian cancer risk factors can provide useful insight into ovarian cancer risk and etiology. We used ribonucleic acid in situ hybridization to assess TNF-α and IL-6 expression on tissue microarray slides from 78 epithelial ovarian carcinomas (51 serous, 12 endometrioid, 7 clear cell, 2 mucinous, 6 other) from a population-based case-control study. Cytokine expression was scored semiquantitatively, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using polytomous logistic regression. TNF-α was expressed in 46% of the tumors, whereas sparse IL-6 expression was seen in only 18% of the tumors. For both markers, expression was most common in high-grade serous carcinomas followed by endometrioid carcinomas. Parity was associated with a reduced risk of TNF-α-positive (OR, 0.3; 95% CI, 0.1-0.7 for 3 or more children versus none) but not TNF-α-negative tumors (P heterogeneity=.02). In contrast, current smoking was associated with a nearly 3-fold increase in risk of TNF-α-negative (OR, 2.8; 95% CI, 1.2-6.6) but not TNF-α-positive tumors (P heterogeneity = .06). Our data suggest that TNF-α expression in ovarian carcinoma varies by histologic subtype and provides some support for the role of inflammation in ovarian carcinogenesis. The novel associations detected in our study need to be validated in a larger cohort of patients in future studies. PMID:27068525

  9. 76 FR 22108 - Proposed Collection; Comment Request; Prostate, Lung, Colorectal and Ovarian Cancer Screening...

    Science.gov (United States)

    2011-04-20

    ... to determine if screening for prostate, lung, colorectal and ovarian cancer can reduce mortality from these cancers which currently cause an estimated 254,570 deaths annually in the U.S. The design is a two... of the trial is cancer specific mortality for each of the four cancer sites (prostate,...

  10. Inhibition of Hec1 expression enhances the sensitivity of human ovarian cancer cells to paclitaxel

    Institute of Scientific and Technical Information of China (English)

    Qing-qing MO; Ping-bo CHEN; Xin JIN; Qian CHEN; Lan TANG; Bei-bei WANG; Ke-zhen LI

    2013-01-01

    Aim:Hec1,a member of the Ndc80 kinetochore complex,is highly expressed in cancers.The aim of this study was to explore the role and mechanism of action of Hec1 with respect to the cytotoxicity of paclitaxel in ovarian cancer.Methods:Thirty ovarian cancer samples and 6 normal ovarian samples were collected.Hec1 expression in these samples was determined with immunohistochemistry.Ovarian cancer cell lines A2780,OV2008,C13K,SKOV3,and CAOV3 and A2780/Taxol were examined.Cell apoptosis and cell cycle analysis were detected with flow cytometric technique.siRNA was used to delete Hec1 in the cells.The expression of related mRNAs and proteins was measured using RT-PCR and Western blot analysis,respectively.Results:Hec1 expression was significantly higher in ovarian cancer samples than in normal ovarian samples,and was associated with paclitaxel-resistance and poor prognosis.Among the 6 ovarian cancer cell lines examined,Hec1 expression was highest in paclitaxelresistant A2780/Taxol cells,and lowest in A2780 cells.Depleting Hec1 in A2780/Taxol cells with siRNA decreased the IC5o value of paclitaxel by more than 10-fold (from 590±26.7 to 45.6±19.4 nmol/L).Depleting Hec1 in A2780 cells had no significant effect on the paclitaxel sensitivity.In paclitaxel-treated A2780/Taxol cells,depleting Hec1 significantly increased the cleaved PARP and Bax protein levels,and decreased the Bcl-xL protein level.Conclusion:Hec1 overexpression is associated with the progression and poor prognosis of ovarian cancer.Inhibition of Hec1 expression can sensitize ovarian cancer cells to paclitaxel.

  11. Identification of novel therapeutic targets in microdissected clear cell ovarian cancers.

    Directory of Open Access Journals (Sweden)

    Michael P Stany

    Full Text Available Clear cell ovarian cancer is an epithelial ovarian cancer histotype that is less responsive to chemotherapy and carries poorer prognosis than serous and endometrioid histotypes. Despite this, patients with these tumors are treated in a similar fashion as all other ovarian cancers. Previous genomic analysis has suggested that clear cell cancers represent a unique tumor subtype. Here we generated the first whole genomic expression profiling using epithelial component of clear cell ovarian cancers and normal ovarian surface specimens isolated by laser capture microdissection. All the arrays were analyzed using BRB ArrayTools and PathwayStudio software to identify the signaling pathways. Identified pathways validated using serous, clear cell cancer cell lines and RNAi technology. In vivo validations carried out using an orthotopic mouse model and liposomal encapsulated siRNA. Patient-derived clear cell and serous ovarian tumors were grafted under the renal capsule of NOD-SCID mice to evaluate the therapeutic potential of the identified pathway. We identified major activated pathways in clear cells involving in hypoxic cell growth, angiogenesis, and glucose metabolism not seen in other histotypes. Knockdown of key genes in these pathways sensitized clear cell ovarian cancer cell lines to hypoxia/glucose deprivation. In vivo experiments using patient derived tumors demonstrate that clear cell tumors are exquisitely sensitive to antiangiogenesis therapy (i.e. sunitinib compared with serous tumors. We generated a histotype specific, gene signature associated with clear cell ovarian cancer which identifies important activated pathways critical for their clinicopathologic characteristics. These results provide a rational basis for a radically different treatment for ovarian clear cell patients.

  12. 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

  13. 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...

  14. Ovarian cancer: emerging concept on cancer stem cells

    OpenAIRE

    Ponnusamy Moorthy P; Batra Surinder K

    2008-01-01

    Abstract Emerging evidence suggests that the capacity of a tumor to grow and propagate is dependent on a small subset of cells within a tumor, termed cancer stem cells. In fact, cancer cells, like stem cells, can proliferate indefinitely through a dysregulated cellular self-renewal capacity. Cancer stem cells may originate due to the distribution into self-renewal and differentiation pathways occurring in multi-potential stem cells, tissue-specific stem cells, progenitor cells and cancer cell...

  15. Transcription factor-microRNA-target gene networks associated with ovarian cancer survival and recurrence.

    Science.gov (United States)

    Delfino, Kristin R; Rodriguez-Zas, Sandra L

    2013-01-01

    The identification of reliable transcriptome biomarkers requires the simultaneous consideration of regulatory and target elements including microRNAs (miRNAs), transcription factors (TFs), and target genes. A novel approach that integrates multivariate survival analysis, feature selection, and regulatory network visualization was used to identify reliable biomarkers of ovarian cancer survival and recurrence. Expression profiles of 799 miRNAs, 17,814 TFs and target genes and cohort clinical records on 272 patients diagnosed with ovarian cancer were simultaneously considered and results were validated on an independent group of 146 patients. Three miRNAs (hsa-miR-16, hsa-miR-22*, and ebv-miR-BHRF1-2*) were associated with both ovarian cancer survival and recurrence and 27 miRNAs were associated with either one hazard. Two miRNAs (hsa-miR-521 and hsa-miR-497) were cohort-dependent, while 28 were cohort-independent. This study confirmed 19 miRNAs previously associated with ovarian cancer and identified two miRNAs that have previously been associated with other cancer types. In total, the expression of 838 and 734 target genes and 12 and eight TFs were associated (FDR-adjusted P-value cancer survival and recurrence, respectively. Functional analysis highlighted the association between cellular and nucleotide metabolic processes and ovarian cancer. The more direct connections and higher centrality of the miRNAs, TFs and target genes in the survival network studied suggest that network-based approaches to prognosticate or predict ovarian cancer survival may be more effective than those for ovarian cancer recurrence. This study demonstrated the feasibility to infer reliable miRNA-TF-target gene networks associated with survival and recurrence of ovarian cancer based on the simultaneous analysis of co-expression profiles and consideration of the clinical characteristics of the patients.

  16. A Single Nucleotide Polymorphism in Catalase Is Strongly Associated with Ovarian Cancer Survival.

    Science.gov (United States)

    Belotte, Jimmy; Fletcher, Nicole M; Saed, Mohammed G; Abusamaan, Mohammed S; Dyson, Gregory; Diamond, Michael P; Saed, Ghassan M

    2015-01-01

    Ovarian cancer is the deadliest of all gynecologic cancers. Recent evidence demonstrates an association between enzymatic activity altering single nucleotide polymorphisms (SNP) with human cancer susceptibility. We sought to evaluate the association of SNPs in key oxidant and antioxidant enzymes with increased risk and survival in epithelial ovarian cancer. Individuals (n = 143) recruited were divided into controls, (n = 94): healthy volunteers, (n = 18), high-risk BRCA1/2 negative (n = 53), high-risk BRCA1/2 positive (n = 23) and ovarian cancer cases (n = 49). DNA was subjected to TaqMan SNP genotype analysis for selected oxidant and antioxidant enzymes. Of the seven selected SNP studied, no association with ovarian cancer risk (Pearson Chi-square) was found. However, a catalase SNP was identified as a predictor of ovarian cancer survival by the Cox regression model. The presence of this SNP was associated with a higher likelihood of death (hazard ratio (HR) of 3.68 (95% confidence interval (CI): 1.149-11.836)) for ovarian cancer patients. Kaplan-Meier survival analysis demonstrated a significant median overall survival difference (108 versus 60 months, pcancer patients, and thus may serve as a prognosticator.

  17. Metformin limits the adipocyte tumor-promoting effect on ovarian cancer.

    Science.gov (United States)

    Tebbe, Calvin; Chhina, Jasdeep; Dar, Sajad A; Sarigiannis, Kalli; Giri, Shailendra; Munkarah, Adnan R; Rattan, Ramandeep

    2014-07-15

    Omental adipocytes promote ovarian cancer by secretion of adipokines, cytokines and growth factors, and acting as fuel depots. We investigated if metformin modulates the ovarian cancer promoting effects of adipocytes. Effect of conditioned media obtained from differentiated mouse 3T3L1 preadipoctes on the proliferation and migration of a mouse ovarian surface epithelium cancer cell line (ID8) was estimated. Conditioned media from differentiated adipocytes increased the proliferation and migration of ID8 cells, which was attenuated by metformin. Metformin inhibited adipogenesis by inhibition of key adipogenesis regulating transcription factors (CEBPα, CEBPß, and SREBP1), and induced AMPK. A targeted Cancer Pathway Finder RT-PCR (real-time polymerase chain reaction) based gene array revealed 20 up-regulated and 2 down-regulated genes in ID8 cells exposed to adipocyte conditioned media, which were altered by metformin. Adipocyte conditioned media also induced bio-energetic changes in the ID8 cells by pushing them into a highly metabolically active state; these effects were reversed by metformin. Collectively, metformin treatment inhibited the adipocyte mediated ovarian cancer cell proliferation, migration, expression of cancer associated genes and bio-energetic changes. Suggesting, that metformin could be a therapeutic option for ovarian cancer at an early stage, as it not only targets ovarian cancer, but also modulates the environmental milieu.

  18. Ovarian cancer: Ion channel and aquaporin expression as novel targets of clinical potential.

    Science.gov (United States)

    Frede, Julia; Fraser, Scott P; Oskay-Özcelik, Gülten; Hong, Yeosun; Ioana Braicu, E; Sehouli, Jalid; Gabra, Hani; Djamgoz, Mustafa B A

    2013-07-01

    Ovarian cancer is associated with limited overall survival, due to problems in early detection and therapy. Membrane ion channels have been proposed to play a significant, concerted role in the cancer process, from initial proliferation to metastasis, and promise to be early, functional biomarkers. We review the evidence for ion channel and aquaporin expression and functioning in human ovarian cancer cells and tissues. In vitro, K(+) channels, mainly voltage-gated, including Ca(2+)-activated channels, have been found to control the cell cycle, as in other cancers. Voltage-gated, volume-regulated and intracellular Cl(-) channels have been detected in vitro and in vivo and shown to be involved in proliferation, adhesion and invasion. Evidence for 'transient receptor potential', voltage-gated sodium and calcium channels, which have been shown to contribute to pathogenesis of other carcinomas, is also emerging in ovarian cancer. Aquaporins may be involved in cell growth, migration and formation of ascites via increased water permeability of micro-vessels. It is concluded that functional expression of ion channels and their regulation by steroid hormones and growth factors are an integral part of ovarian cancer development and progression. Furthermore, ion channels may be involved in multidrug resistance, commonly associated with treatment of ovarian cancer. We propose that ion channel studies can facilitate our understanding of the pathobiology of ovarian cancer and, ultimately, can serve as viable novel targets for its clinical management. PMID:23683551

  19. A Nonsynonymous Polymorphism in IRS1 Modifies Risk of Developing Breast and Ovarian Cancers in BRCA1 and Ovarian Cancer in BRCA2 Mutation Carriers

    NARCIS (Netherlands)

    Ding, Yuan C.; McGuffog, Lesley; Healey, Sue; Friedman, Eitan; Laitman, Yael; Shani-Paluch-Shimon, [No Value; Kaufman, Bella; Liljegren, Annelie; Lindblom, Annika; Olsson, Hakan; Kristoffersson, Ulf; Stenmark-Askmalm, Marie; Melin, Beatrice; Domchek, Susan M.; Nathanson, Katherine L.; Rebbeck, Timothy R.; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Gronwald, Jacek; Huzarski, Tomasz; Cybulski, Cezary; Byrski, Tomasz; Osorio, Ana; Ramony Cajal, Teresa; Stavropoulou, Alexandra V.; Benitez, Javier; Hamann, Ute; Rookus, Matti; Aalfs, Cora M.; de Lange, Judith L.; Meijers-Heijboer, Hanne E. J.; Oosterwijk, Jan C.; van Asperen, Christi J.; Garcia, Encarna B. Gomez; Hoogerbrugge, Nicoline; Jager, Agnes; van der Luijt, Rob B.; Easton, Douglas F.; Peock, Susan; Frost, Debra; Ellis, Steve D.; Platte, Radka; Fineberg, Elena; Evans, D. Gareth; Lalloo, Fiona; Izatt, Louise; Eeles, Ros; Adlard, Julian; Davidson, Rosemarie; Eccles, Diana; Cole, Trevor; Cook, Jackie; Brewer, Carole; Tischkowitz, Marc; Godwin, Andrew K.; Pathak, Harsh; Stoppa-Lyonnet, Dominique; Sinilnikova, Olga M.; Mazoyer, Sylvie; Barjhoux, Laure; Leone, Melanie; Gauthier-Villars, Marion; Caux-Moncoutier, Virginie; de Pauw, Antoine; Hardouin, Agnes; Berthet, Pascaline; Dreyfus, Helene; Ferrer, Sandra Fert; Collonge-Rame, Marie-Agnes; Sokolowska, Johanna; Buys, Saundra; Daly, Mary; Miron, Alex; Terry, Mary Beth; Chung, Wendy; John, Esther M.; Southey, Melissa; Goldgar, David; Singer, Christian F.; Tea, Muy-Kheng Maria; Gschwantler-Kaulich, Daphne; Fink-Retter, Anneliese; Hansen, Thomas V. O.; Ejlertsen, Bent; Johannsson, Oskar T.; Offit, Kenneth; Sarrel, Kara; Gaudet, Mia M.; Vijai, Joseph; Robson, Mark; Piedmonte, Marion R.; Andrews, Lesley; Cohn, David; DeMars, Leslie R.; DiSilvestro, Paul; Rodriguez, Gustavo; Toland, Amanda Ewart; Montagna, Marco; Agata, Simona; Imyanitov, Evgeny; Isaacs, Claudine; Janavicius, Ramunas; Lazaro, Conxi; Blanco, Ignacio; Ramus, Susan J.; Sucheston, Lara; Karlan, Beth Y.; Gross, Jenny; Ganz, Patricia A.; Beattie, Mary S.; Schmutzler, Rita K.; Wappenschmidt, Barbara; Meindl, Alfons; Arnold, Norbert; Niederacher, Dieter; Preisler-Adams, Sabine; Gadzicki, Dorotehea; Varon-Mateeva, Raymonda; Deissler, Helmut; Gehrig, Andrea; Sutter, Christian; Kast, Karin; Nevanlinna, Heli; Aittomaki, Kristiina; Simard, Jacques; Spurdle, Amanda B.; Beesley, Jonathan; Chen, Xiaoqing; Tomlinson, Gail E.; Weitzel, Jeffrey; Garber, Judy E.; Olopade, Olufunmilayo I.; Rubinstein, Wendy S.; Tung, Nadine; Blum, Joanne L.; Narod, Steven A.; Brummel, Sean; Gillen, Daniel L.; Lindor, Noralane; Fredericksen, Zachary; Pankratz, Vernon S.; Couch, Fergus J.; Radice, Paolo; Peterlongo, Paolo; Greene, Mark H.; Loud, Jennifer T.; Mai, Phuong L.; Andrulis, Irene L.; Glendon, Gord; Ozcelik, Hilmi; Gerdes, Anne-Marie; Thomassen, Mads; Jensen, Uffe Birk; Skytte, Anne-Bine; Caligo, Maria A.; Lee, Andrew; Chenevix-Trench, Georgia; Antoniou, Antonis C.; Neuhausen, Susan L.

    2012-01-01

    Background: We previously reported significant associations between genetic variants in insulin receptor substrate 1 (IRS1) and breast cancer risk in women carrying BRCA1 mutations. The objectives of this study were to investigate whether the IRS1 variants modified ovarian cancer risk and were assoc

  20. A nonsynonymous polymorphism in IRS1 modifies risk of developing breast and ovarian cancers in BRCA1 and ovarian cancer in BRCA2 mutation carriers

    NARCIS (Netherlands)

    Y.C. Ding (Yuan); L. McGuffog (Lesley); S. Healey (Sue); E. Friedman (Eitan); Y. Laitman (Yael); S.-P. Shimon (Shani-Paluch); B. Kaufman (Bella); A. Liljegren (Annelie); A. Lindblom (Annika); H. Olsson; U. Kristoffersson (Ulf); M. Stenmark-Askmalm (M.); B. Melin (Beatrice); S.M. Domchek (Susan); K.L. Nathanson (Katherine); R. Rebbeck (Timothy); A. Jakubowska (Anna); J. Lubinski (Jan); K. Jaworska (Katarzyna); K. Durda (Katarzyna); J. Gronwald (Jacek); T. Huzarski (Tomasz); C. Cybulski (Cezary); T. Byrski (Tomasz); A. Osorio (Ana); T.R. Cajal; A. Stavropoulou (Alexandra); J. Benítez (Javier); U. Hamann (Ute); M.A. Rookus (Matti); C.M. Aalfs (Cora); J.L. de Lange (J.); E.J. Meijers-Heijboer (Hanne); J.C. Oosterwijk (Jan); C.J. van Asperen (Christi); E.B. Gómez García (Encarna); N. Hoogerbrugge (Nicoline); A. Jager (Agnes); R.B. van der Luijt (Rob); D.F. Easton (Douglas); S. Peock (Susan); D. Frost (Debra); S.D. Ellis (Steve); R. Platte (Radka); E. Fineberg (Elena); D.G. Evans (Gareth); F. Lalloo (Fiona); L. Izatt (Louise); R. Eeles (Rosalind); J.W. Adlard (Julian); R. Davidson (Rosemarie); D. Eccles (Diana); T.J. Cole (Trevor); J. Cook (Jackie); C. Brewer (Carole); M. Tischkowitz (Marc); A.K. Godwin (Andrew); S.S. Pathak; D. Stoppa-Lyonnet (Dominique); O. Sinilnikova (Olga); S. Mazoyer (Sylvie); L. Barjhoux (Laure); M. Léone (Mélanie); M. Gauthier-Villars (Marion); V. Caux-Moncoutier (Virginie); A. de Pauw (Antoine); A. Hardouin (Agnès); P. Berthet (Pascaline); H. Dreyfus (Hélène); S.F. Ferrer; M.-A. Collonge-Rame; J. Sokolowska (Johanna); S.S. Buys (Saundra); M.B. Daly (Mary); A. Miron (Alexander); M.-B. Terry (Mary-Beth); W. Chung (Wendy); E.M. John (Esther); M.C. Southey (Melissa); D. Goldgar (David); C.F. Singer (Christian); M.-K. Tea; D. Gschwantler-Kaulich (Daphne); A. Fink-Retter (Anneliese); T.V.O. Hansen (Thomas); B. Ejlertsen (Bent); O.T. Johannson (Oskar); K. Offit (Kenneth); K. Sarrel (Kara); M.M. Gaudet (Mia); J. Vijai (Joseph); M. Robson (Mark); M. Piedmonte (Marion); L. Andrews (Lesley); D.E. Cohn (David); L.R. DeMars (Leslie); P. DiSilvestro (Paul); G.C. Rodriguez (Gustavo); A.E. Toland (Amanda); M. Montagna (Marco); S. Agata (Simona); E.N. Imyanitov (Evgeny); C. Isaacs (Claudine); R. Janavicius (Ramunas); C. Lazaro (Conxi); I. Blanco (Ignacio); S.J. Ramus (Susan); L. Sucheston (Lara); B. Karlan; J. Gross (Jenny); P.A. Ganz (Patricia); M.S. Beattie (Mary); R.K. Schmutzler (Rita); B. Wapenschmidt (Barbara); A. Meindl (Alfons); N. Arnold (Norbert); D. Niederacher (Dieter); S. Preisler-Adams (Sabine); D. Gadzicki (Dorothea); R. Varon-Mateeva (Raymonda); H. Deissler (Helmut); P.A. Gehrig (Paola A.); C. Sutter (Christian); K. Kast (Karin); H. Nevanlinna (Heli); K. Aittomäki (Kristiina); J. Simard (Jacques); A.B. Spurdle (Amanda); J. Beesley (Jonathan); X. Chen (Xiaoqing); G. Tomlinson (Gail); J.N. Weitzel (Jeffrey); J. Garber; O.I. Olopade (Olofunmilayo); W.S. Rubinstein (Wendy); N. Tung (Nadine); J.L. Blum (Joann); S. Narod (Steven); S. Brummel (Sean); D.L. Gillen (Daniel); N.M. Lindor (Noralane); Z. Fredericksen (Zachary); V.S. Pankratz (Shane); F.J. Couch (Fergus); P. Radice (Paolo); P. Peterlongo (Paolo); M.H. Greene (Mark); J.T. Loud (Jennifer); P.L. Mai (Phuong); I.L. Andrulis (Irene); G. Glendon (Gord); H. Ozcelik (Hilmi); A-M. Gerdes (Anne-Marie); M. Thomassen (Mads); U.B. Jensen; A.-B. Skytte (Anne-Bine); M.A. Caligo (Maria); A. Lee (Andrew); G. Chenevix-Trench (Georgia); A.C. Antoniou (Antonis); S.L. Neuhausen (Susan)

    2012-01-01

    textabstractBackground: We previously reported significant associations between genetic variants in insulin receptor substrate 1 (IRS1) and breast cancer risk inwomen carrying BRCA1 mutations. The objectives of this study were to investigate whether the IRS1 variants modified ovarian cancer risk and