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Sample records for murine ovarian cancer

  1. Icodextrin enhances survival in an intraperitoneal ovarian cancer murine model utilizing gene therapy.

    Science.gov (United States)

    Rocconi, Rodney P; Numnum, Michael T; Zhu, Zeng B; Lu, Baogen; Wang, Minghui; Rivera, Angel A; Stoff-Khalili, Mariam; Alvarez, Ronald D; Curiel, David T; Makhija, Sharmila

    2006-12-01

    Icodextrin, a novel glucose polymer solution utilized for peritoneal dialysis, has been demonstrated to have prolonged intraperitoneal (IP) instillation volumes in comparison to standard PBS solutions. In an animal model of ovarian cancer, we explored whether a survival advantage exists utilizing icodextrin rather than PBS as a delivery solution for an infectivity enhanced virotherapy approach. Initial experiments evaluated whether icodextrin would adversely affect replication of a clinical grade infectivity enhanced conditionally replicative adenovirus (Delta24-RGD). Virus was added to prepared blinded solutions of PBS or icodextrin (20%) and then evaluated in vitro in various human ovarian cancer cell lines (SKOV3.ip1, PA-1, and Hey) and in vivo in a SKOV3.ip1 human ovarian cancer IP murine model. Viral replication was measured by detecting adenovirus E4 gene levels utilizing QRT-PCR. Survival was subsequently evaluated in a separate SKOV3.ip1 ovarian cancer IP murine model. Cohorts of mice were treated in blinded fashion with PBS alone, icodextrin alone, PBS+Delta24-RGD, or icodextrin+Delta24-RGD. Survival data were plotted on Kaplan-Meier curve and statistical calculations performed using the log-rank test. There was no adverse affect of icodextrin on vector replication in the ovarian cancer cell lines nor murine model tumor samples evaluated. Median survival in the IP treated animal cohorts was 23 days for the PBS group, 40 days for the icodextrin group, 65 days for the PBS+Delta24-RGD group, and 105 days for icodextrin+Delta24-RGD (p=0.023). Of note, 5 of the 10 mice in the icodextrin+Delta24-RGD group were alive at the end of the study period, all without evidence of tumor (120 days). These experiments suggest that the use of dialysates such as icodextrin may further enhance the therapeutic effects of novel IP virotherapy and other gene therapy strategies for ovarian cancer. Phase I studies utilizing icodextrin-based virotherapy for ovarian cancer are

  2. Ovarian Cancer

    Science.gov (United States)

    ... deaths than other female reproductive cancers. The sooner ovarian cancer is found and treated, the better your chance for recovery. But ovarian cancer is hard to detect early. Women with ovarian ...

  3. Ovarian Cancer

    Science.gov (United States)

    ... the ovary, fallopian tube, and peritoneum: Epidemiology and risk factors. http://www.uptodate.com/home. Accessed Feb. 18, 2014. Havrilesky LJ, et al. Oral contraceptive pills as primary prevention for ovarian cancer: A systematic ...

  4. Cancer testis antigen vaccination affords long-term protection in a murine model of ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Maurizio Chiriva-Internati

    Full Text Available Sperm protein (Sp17 is an attractive target for ovarian cancer (OC vaccines because of its over-expression in primary as well as in metastatic lesions, at all stages of the disease. Our studies suggest that a Sp17-based vaccine can induce an enduring defense against OC development in C57BL/6 mice with ID8 cells, following prophylactic and therapeutic treatments. This is the first time that a mouse counterpart of a cancer testis antigen (Sp17 was shown to be expressed in an OC mouse model, and that vaccination against this antigen significantly controlled tumor growth. Our study shows that the CpG-adjuvated Sp17 vaccine overcomes the issue of immunologic tolerance, the major barrier to the development of effective immunotherapy for OC. Furthermore, this study provides a better understanding of OC biology by showing that Th-17 cells activation and contemporary immunosuppressive T-reg cells inhibition is required for vaccine efficacy. Taken together, these results indicate that prophylactic and therapeutic vaccinations can induce long-standing protection against OC and delay tumor growth, suggesting that this strategy may provide additional treatments of human OC and the prevention of disease onset in women with a family history of OC.

  5. Phase III trial of intraperitoneal therapy with yttrium-90-labeled HMFG1 murine monoclonal antibody in patients with epithelial ovarian cancer after a surgically defined complete remission.

    NARCIS (Netherlands)

    Verheijen, R.H.; Massuger, L.F.A.G.; Benigno, B.B.; Epenetos, A.A.; Lopes, A.; Soper, J.T.; Markowska, J.; Vyzula, R.; Jobling, T.; Stamp, G.; Spiegel, G.; Thurston, D.; Falke, T.; Lambert, J.; Seiden, M.V.

    2006-01-01

    PURPOSE: This was a multinational, open-label, randomized phase III trial comparing yttrium-90-labeled murine HMFG1 (90Y-muHMFG1) plus standard treatment versus standard treatment alone in patients with epithelial ovarian cancer (EOC) who had attained a complete clinical remission after

  6. How Is Ovarian Cancer Diagnosed?

    Science.gov (United States)

    ... Cancer Early Detection, Diagnosis, and Staging How Is Ovarian Cancer Diagnosed? If you have symptoms of ovarian cancer ... Ask Your Doctor About Ovarian Cancer? More In Ovarian Cancer About Ovarian Cancer Causes, Risk Factors, and Prevention ...

  7. Ultrasound Molecular Imaging in a Human CD276 Expression-Modulated Murine Ovarian Cancer Model

    Science.gov (United States)

    Lutz, Amelie M.; Bachawal, Sunitha V.; Drescher, Charles W.; Pysz, Marybeth A.; Willmann, Jürgen K.; Gambhir, Sanjiv Sam

    2014-01-01

    Purpose To develop a mouse ovarian cancer model that allows modulating the expression levels of human vascular targets in mouse xenograft tumors and to test whether expression of CD276 during tumor angiogenesis can be visualized by molecularly targeted ultrasound in vivo. Materials and Methods CD276-expressing MS-1 mouse endothelial cells were engineered and used for co-injection with 2008 human ovarian cancer cells for subcutaneous xenograft tumor induction in 15 nude mice. Fourteen control mice were injected with 2008 cells only. After confirming their binding specificity in flow chamber cell attachment studies, anti CD276 antibody-functionalized contrast microbubbles were used for in vivo CD276-targeted contrast-enhanced ultrasound imaging. Results CD276-targeted ultrasound imaging signal was significantly higher (P=0.006) in mixed MS1/2008 tumors compared to control tumors. Compared to control microbubbles the ultrasound signal using CD276-targeted microbubbles was significantly higher (P=0.002) and blocking with purified anti-CD276 antibody significantly decreased (P=0.0096) the signal in mixed MS-1/2008 tumors. Immunofluorescence analysis of the tumor tissue confirmed higher quantitative immunofluorescence signal in mixed MS-1/2008 tumors than in control 2008 only tumors, but showed not significantly different (P=0.54) microvessel density. Conclusion Our novel small animal model allows for modulating the expression of human tumor-associated vascular endothelial imaging targets in a mouse host and these expression differences can be visualized non-invasively by ultrasound molecular imaging. The animal model can be applied to other human vascular targets and may facilitate the preclinical development of new imaging probes such as microbubbles targeted at human vascular markers not expressed in mice. PMID:24389327

  8. How Is Ovarian Cancer Staged?

    Science.gov (United States)

    ... Cancer Early Detection, Diagnosis, and Staging How Is Ovarian Cancer Staged? Staging is the process of finding out ... Ask Your Doctor About Ovarian Cancer? More In Ovarian Cancer About Ovarian Cancer Causes, Risk Factors, and Prevention ...

  9. Screening for Ovarian Cancer

    Science.gov (United States)

    Understanding Task Force Recommendations Screening for Ovarian Cancer The U.S. Preventive Services Task Force (Task Force) has issued a final recommendation on Screening for Ovarian Cancer . This recommendation is for ...

  10. 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....

  11. Ovarian Autoantibodies Predict Ovarian Cancer

    Science.gov (United States)

    2010-11-01

    of carcinogenesis is supported by literature reports; for example, in patients with chronic hepatitis (which predisposes to liver cancer) specific...Immunohistochemical 502 expression of molecular markers in an avian model: a potential model for preclinical evaluation 503 of agents for ovarian cancer... avian S1P1, we 180 used a commercially available polyclonal antibody against human S1P1 for Western blotting and 181 immunohistochemical experiments

  12. Symptoms of Ovarian Cancer

    Science.gov (United States)

    ... Informed Cancer Home What Are the Symptoms of Ovarian Cancer? Language: English Español (Spanish) Recommend on Facebook Tweet Share Compartir Gynecologic cancer symptoms diaries Ovarian cancer may cause the following signs and symptoms— Vaginal ...

  13. Ovarian Cancer FAQ

    Science.gov (United States)

    ... increased risk of breast cancer and ovarian cancer. CA 125: A substance in the blood that may increase in the presence of some cancerous tumors. Colonoscopy: An exam of the entire colon using a small, lighted instrument. Computed Tomography: A ...

  14. Multiple metastases from ovarian cancer

    African Journals Online (AJOL)

    Epithelial ovarian cancer is one of the most common ovarian tumours. Ovarian cancer affects women ... manifested by parenchymal liver or lung metastases, or .... Primary central nervous system recurrence after paclitaxel therapy for epithelial ...

  15. Ovarian Cancer Stage II

    Science.gov (United States)

    ... hyphen, e.g. -historical Searches are case-insensitive Ovarian Cancer Stage II Add to My Pictures View /Download : ... 1650x675 View Download Large: 3300x1350 View Download Title: Ovarian Cancer Stage II Description: Three-panel drawing of stage ...

  16. Ovarian Cancer Stage IIIC

    Science.gov (United States)

    ... hyphen, e.g. -historical Searches are case-insensitive Ovarian Cancer Stage IIIC Add to My Pictures View /Download : ... 1530x1350 View Download Large: 3060x2700 View Download Title: Ovarian Cancer Stage IIIC Description: Drawing of stage IIIC shows ...

  17. Ovarian Cancer Stage I

    Science.gov (United States)

    ... hyphen, e.g. -historical Searches are case-insensitive Ovarian Cancer Stage I Add to My Pictures View /Download : ... 1650x675 View Download Large: 3300x1350 View Download Title: Ovarian Cancer Stage I Description: Three-panel drawing of stage ...

  18. Ovarian Cancer Stage IV

    Science.gov (United States)

    ... organs and tissues outside the abdomen, including the lung, liver, bone, and lymph nodes in the groin. Topics/Categories: Anatomy -- Gynecologic Cancer Types -- Ovarian Cancer Cells or Tissue -- ...

  19. Can Ovarian Cancer Be Found Early?

    Science.gov (United States)

    ... Ovarian Cancer Early Detection, Diagnosis, and Staging Can Ovarian Cancer Be Found Early? About 20% of ovarian cancers ... cancer in its earliest stage. Ways to find ovarian cancer early Regular women's health exams During a pelvic ...

  20. Ovarian Cancer and Comorbidity

    DEFF Research Database (Denmark)

    Noer, Mette Calundann; Sperling, Cecilie Dyg; Ottesen, Bent

    2017-01-01

    OBJECTIVES: Comorbidity influences survival in ovarian cancer, but the causal relations between prognosis and comorbidity are not well characterized. The aim of this study was to investigate the associations between comorbidity, system delay, the choice of primary treatment, and survival in Danish...... ovarian cancer patients. METHODS: This population-based study was conducted on data from 5317 ovarian cancer patients registered in the Danish Gynecological Cancer Database. Comorbidity was classified according to the Charlson Comorbidity Index and the Ovarian Cancer Comorbidity Index. Pearson χ test...... and multivariate logistic regression analyses were used to investigate the association between comorbidity and primary outcome measures: primary treatment ("primary debulking surgery" vs "no primary surgery") and system delay (more vs less than required by the National Cancer Patient Pathways [NCPPs]). Cox...

  1. What Are the Key Statistics about Ovarian Cancer?

    Science.gov (United States)

    ... Ovarian Cancer What Are the Key Statistics About Ovarian Cancer? The American Cancer Society estimates for ovarian cancer ... in Ovarian Cancer Research and Treatment? More In Ovarian Cancer About Ovarian Cancer Causes, Risk Factors, and Prevention ...

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

    Science.gov (United States)

    ... Ovarian Cancer About Ovarian Cancer What's New in Ovarian Cancer Research and Treatment? Risk factors and causes Scientists ... in Ovarian Cancer Research and Treatment? More In Ovarian Cancer About Ovarian Cancer Causes, Risk Factors, and Prevention ...

  3. Ovarian cancer surgery

    DEFF Research Database (Denmark)

    Seibaek, Lene; Blaakaer, Jan; Petersen, Lone Kjeld

    2013-01-01

    PURPOSE: The study objective was to survey general health and coping in women undergoing ovarian cancer surgery, and subsequently to develop and test a supportive care intervention. METHODS/MATERIALS: Women who underwent surgery on the suspicion of ovarian cancer participated in a follow...... standard levels. Concerning mental health, levels were below standard during the entire period, but did improve with time, also in women in whom the potential cancer diagnosis was refuted. The preoperative differences between these groups leveled out postoperatively in terms of physical health. At the end...

  4. Ovarian Cancer FAQ

    Science.gov (United States)

    ... Gyn): A physician with special skills, training, and education in women’s health. Ovarian Cancer: Cancer that affects one or both of the ovaries. Ovaries: The paired organs in the female reproductive system that contain the eggs released at ovulation ...

  5. 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

  6. TP53 and ovarian cancer

    NARCIS (Netherlands)

    M. Schuijer (Monique); P.M.J.J. Berns (Els)

    2003-01-01

    textabstractOvarian cancer represents the fourth most frequent type of cancer among females and is the leading cause of death from gynecological cancer in the western world. This review describes gene alterations in ovarian cancer. Specific emphasis is placed on genetic alterations and the prevalenc

  7. What Will Happen After Treatment for Ovarian Cancer?

    Science.gov (United States)

    ... After Treatment What Will Happen After Treatment for Ovarian Cancer? For some people with ovarian cancer, treatment may ... If Ovarian Cancer Treatment Stops Working More In Ovarian Cancer About Ovarian Cancer Causes, Risk Factors, and Prevention ...

  8. Antiangiogenic therapies in ovarian cancer

    OpenAIRE

    Reinthaller, Alexander

    2016-01-01

    Summary Angiogenesis plays a pivotal role in normal ovarian physiology as well as in the formation and progression of ovarian cancer. Several well-designed phase II and III trials studied the efficacy of antiangiogenic agents in advanced ovarian cancer. The results of these trials demonstrated significantly prolonged progression-free survival when antiangiogenic agents were used as a maintenance therapy. To date, no effect on overall survival could be ascertained. The most widely studied anti...

  9. 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...... of Medicinal Product Statistics provided individually updated exposure information. The National Cancer Register and Pathology Register provided ovarian cancer incidence data. Information on confounding factors and effect modifiers was from other national registers. Poisson regression analyses with 5-year age...... 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...

  10. 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.

  11. CA125 in ovarian cancer

    DEFF Research Database (Denmark)

    Duffy, M J; Bonfrer, J M; Kulpa, J

    2005-01-01

    value in the detection of early ovarian cancer. At present, therefore, CA125, either alone or in combination with other modalities, cannot be recommended for screening for ovarian cancer in asymptomatic women outside the context of a randomized controlled trial. Preoperative levels in postmenopausal...... women, however, may aid the differentiation of benign and malignant pelvic masses. Serial levels during chemotherapy for ovarian cancer are useful for assessing response to treatment. Although serial monitoring following initial chemotherapy can lead to the early detection of recurrent disease......CA125 is currently the most widely used tumor marker for ovarian epithelial cancer. The aim of this article is to provide guidelines for the routine clinical use of CA125 in patients with ovarian cancer. Due to lack of sensitivity for stage I disease and lack of specificity, CA125 is of little...

  12. Ovarian cancer: the neglected diagnosis.

    Science.gov (United States)

    Yawn, Barbara P; Barrette, Brigitte A; Wollan, Peter C

    2004-10-01

    To investigate presenting signs and symptoms of ovarian cancer and stage of tumor in a community cohort of women with the diagnosis of ovarian cancer. We reviewed retrospectively the medical records of all women who sought primary and specialty care in Olmsted County, Minnesota, between January 1, 1985, and December 31, 1997, to evaluate presenting symptoms, time from first symptom to diagnosis of ovarian cancer, and stage of tumor at diagnosis. Of 107 women with a diagnosis of ovarian cancer, the most commonly documented presenting symptom was crampy abdominal pain. Urinary symptoms and abdominal pain were the most commonly documented presenting symptom in patients with stage I and II ovarian cancers, whereas abdominal pain and increased abdominal girth were the most commonly documented symptoms in patients with stage III and IV cancer. Approximately 15% of tumors (n = 15) were found during routine evaluations or during a procedure for another problem. Less than 25% of presenting symptoms (n = 24 women) related directly to the pelvis or were more traditional gynecologic symptoms. Delays in women seeking medical care, health care system issues, competing medical conditions, physicians' failure to follow up, and women not returning for follow-up were associated with longer time to diagnosis. Both stage I and II cancer are associated with symptoms, but few symptoms are directly related to the reproductive pelvic organs or unique to ovarian cancer. A longer interval from first sign or symptom to diagnosis of ovarian cancer is associated with both patient and health care system factors.

  13. Subtypes of Ovarian Cancer and Ovarian Cancer Screening

    Science.gov (United States)

    Koshiyama, Masafumi; Matsumura, Noriomi; Konishi, Ikuo

    2017-01-01

    Ovarian cancer is the foremost cause of gynecological cancer death in the developed world, as it is usually diagnosed at an advanced stage. In this paper we discuss current issues, the efficacy and problems associated with ovarian cancer screening, and compare the characteristics of ovarian cancer subtypes. There are two types of ovarian cancer: Type I carcinomas, which are slow-growing, indolent neoplasms thought to arise from a precursor lesion, which are relatively common in Asia; and Type II carcinomas, which are clinically aggressive neoplasms that can develop de novo from serous tubal intraepithelial carcinomas (STIC) and/or ovarian surface epithelium and are common in Europe and the USA. One of the most famous studies on the subject reported that annual screening using CA125/transvaginal sonography (TVS) did not reduce the ovarian cancer mortality rate in the USA. In contrast, a recent study in the UK showed an overall average mortality reduction of 20% in the screening group. Another two studies further reported that the screening was associated with decreased stage at detection. Theoretically, annual screening using CA125/TVS could easily detect precursor lesions and could be more effective in Asia than in Europe and the USA. The detection of Type II ovarian carcinoma at an early stage remains an unresolved issue. The resolving power of CA125 or TVS screening alone is unlikely to be successful at resolving STICs. Biomarkers for the early detection of Type II carcinomas such as STICs need to be developed. PMID:28257098

  14. Molecular Imaging of Ovarian Cancer

    OpenAIRE

    Sharma, Sai Kiran; Nemieboka, Brandon; Sala, Evis; Lewis, Jason S.; Zeglis, Brian M

    2016-01-01

    Ovarian cancer is the most lethal gynecologic malignancy and the fifth leading cause of cancer-related death in women. Over the past decade, medical imaging has played an increasingly valuable role in the diagnosis, staging, and treatment planning of the disease. In this “Focus on Molecular Imaging” review, we seek to provide a brief yet informative survey of the current state of the molecular imaging of ovarian cancer. The article is divided into sections according to modality, covering rece...

  15. Regulator of G-Protein Signaling 5 Reduces HeyA8 Ovarian Cancer Cell Proliferation and Extends Survival in a Murine Tumor Model

    Directory of Open Access Journals (Sweden)

    Molly K. Altman

    2012-01-01

    Full Text Available The regulator of G-protein signaling 5 (RGS5 belongs to a family of GTPase activators that terminate signaling cascades initiated by extracellular mediators and G-protein-coupled receptors. RGS5 has an interesting dual biological role. One functional RGS5 role is as a pericyte biomarker influencing the switch to angiogenesis during malignant progression. Its other functional role is to promote apoptosis in hypoxic environments. We set out to clarify the extent to which RGS5 expression regulates tumor progression—whether it plays a pathogenic or protective role in ovarian tumor biology. We thus constructed an inducible gene expression system to achieve RGS5 expression in HeyA8-MDR ovarian cancer cells. Through this we observed that inducible RGS5 expression significantly reduces in vitro BrdU-positive HeyA8-MDR cells, although this did not correlate with a reduction in tumor volume observed using an in vivo mouse model of ovarian cancer. Interestingly, mice bearing RGS5-expressing tumors demonstrated an increase in survival compared with controls, which might be attributed to the vast regions of necrosis observed by pathological examination. Additionally, mice bearing RGS5-expressing tumors were less likely to have ulcerated tumors. Taken together, this data supports the idea that temporal expression and stabilization of RGS5 could be a valuable tactic within the context of a multicomponent approach for modulating tumor progression.

  16. What Should You Ask Your Doctor about Ovarian Cancer?

    Science.gov (United States)

    ... Staging What Should You Ask Your Doctor About Ovarian Cancer? It is important for you to have honest, ... Ask Your Doctor About Ovarian Cancer? More In Ovarian Cancer About Ovarian Cancer Causes, Risk Factors, and Prevention ...

  17. [Oxaliplatin and ovarian cancer].

    Science.gov (United States)

    Dieras, Véronique; Girre, Véronique; Guilhaume, Marie-Noëlle; Laurence, Valérie; Mignot, Laurent

    2006-02-01

    Oxaliplatin was brought into clinical evaluation in ovarian cancer because of the in vitro and in vivo antitumor activity observed in experimental models resistant to cisplatin. As single agent at 130 mg/m2 every 3 weeks, the objective response rates rage from 16% to 29% in patients treated after failure of one or two regimens. As first line, in a randomized trial cyclophosphamide-cisplatin versus cyclophosphamide-oxaliplatine, no significant statistical differences were observed in efficacy parameters (response rate, progression free survival and overall survival). The toxicity profile seemed to favor the oxaliplatin arm. Many associations with other available active drugs as taxanes, gemcitabine and liposomal doxorubicin were performed with promising results.

  18. FAU regulates carboplatin resistance in ovarian cancer.

    Science.gov (United States)

    Moss, Esther L; Mourtada-Maarabouni, Mirna; Pickard, Mark R; Redman, Charles W; Williams, Gwyn T

    2010-01-01

    The development of chemotherapy resistance by cancer cells is complex, using different mechanisms and pathways. The gene FAU (Finkel-Biskis-Reilly murine sarcoma virus (FBR-MuSV)-associated ubiquitously expressed gene) was identified through functional expression cloning and previous data have shown that overexpression enhances apoptosis in several cell types. We demonstrate that the expression of FAU was reduced in the A2780cis (cisplatin resistant subclone of A2780) cell line compared with the A2780 ovarian cancer cell line, and was directly related to the cell line's sensitivity to carboplatin. Downregulation of FAU in the A2780 cell line by transfection with two predesigned short-interfering RNAs (siRNAs) to FAU resulted in a significant increase in resistance to carboplatin-induced cell death. Downregulation resulted in increased cell viability and reduced apoptosis after 72 hr of drug treatment compared with the negative controls (Kruskal-Wallis P = 0.0002). Transfection of the A2780cis cell line with the pcDNA3 plasmid containing FAU was associated with increased sensitivity to carboplatin-induced apoptosis, with decreased cell viability and increased apoptosis (Mann Whitney P FAU was examined by quantitative real-time reverse transcriptase polymerase chain reaction in normal and malignant ovarian tissue. A significant reduction in the expression of FAU was seen in the malignant compared with normal ovarian samples (Kruskal-Wallis P = 0.0261). These data support a role for FAU in the regulation of platinum-resistance in ovarian cancer. Further research is needed into the apoptotic pathway containing FAU to investigate the potential for targeted therapies to increase or restore the platinum sensitivity of ovarian cancer.

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

    Science.gov (United States)

    2017-02-19

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

  20. Stage at diagnosis and ovarian cancer survival

    DEFF Research Database (Denmark)

    Maringe, Camille; Walters, Sarah; Butler, John;

    2012-01-01

    We investigate what role stage at diagnosis bears in international differences in ovarian cancer survival.......We investigate what role stage at diagnosis bears in international differences in ovarian cancer survival....

  1. Imaging diagnostics in ovarian cancer

    DEFF Research Database (Denmark)

    Fog, Sigrid Marie Kasper Kasper; Dueholm, Margit; Marinovskij, Edvard;

    2017-01-01

    OBJECTIVE: To analyze the ability of magnetic resonance imaging (MRI) and systematic evaluation at surgery to predict optimal cytoreduction in primary advanced ovarian cancer and to develop a preoperative scoring system for cancer staging. STUDY DESIGN: Preoperative MRI and standard laparotomy were...... performed in 99 women with either ovarian or primary peritoneal cancer. Using univariate and multivariate logistic regression analysis of a systematic description of the tumor in nine abdominal compartments obtained by MRI and during surgery plus clinical parameters, a scoring system was designed....... MRI is able to assess ovarian cancer with peritoneal carcinomatosis with satisfactory concordance with laparotomic findings. This scoring system could be useful as a clinical guideline and should be evaluated and developed further in larger studies....

  2. LAG3 and PD1 co-inhibitory molecules collaborate to limit CD8+ T cell signaling and dampen antitumor immunity in a murine ovarian cancer model.

    Science.gov (United States)

    Huang, Ruea-Yea; Eppolito, Cheryl; Lele, Shashikant; Shrikant, Protul; Matsuzaki, Junko; Odunsi, Kunle

    2015-09-29

    The immune co-inhibitory receptors lymphocyte activation gene-3 (LAG3) and programmed cell death 1 (PD1) synergistically contribute to autoimmunity and tumor evasion. Here we demonstrate how they collaborate and interact to regulate T cell function. We first show that LAG3 and PD1 are co-expressed on both OVA-specific and non-specific T cells infiltrating murine ovarian tumors. Dual antibody blockade or genetic knockout of LAG3 and PD1 significantly enhanced T effector function and delayed tumor growth. LAG3 and PD1 co-localized in activated CD8+ T cells in vitro at the trans-Golgi vesicles, early/recycling endosomal compartments, lysosomes, and microtubule organizing center. Importantly, LAG3 and PD1 cluster with pLck at the immunological synapse. Reciprocal immunoprecipitation of T cell extracts revealed physical interaction between LAG3 and PD1. Mutational analyses indicate that the cytoplasmic domain of LAG3 is not absolutely required for its association with PD1, while the ITIM and ITSM of PD1 are necessary for its association with LAG3. Finally, LAG3 protein also associates with the Src-homology-2 domain-containing phosphatases (SHP1/2) which are known to be recruited by PD1 during T cell signaling. Our data indicate that the association of LAG3 with PD1 contributes to their rapid trafficking to the immunological synapse, leading to a synergistic inhibitory effect on T cell signaling.

  3. Genetic Modifiers of Ovarian Cancer

    Science.gov (United States)

    2014-08-01

    variants and cancer risk in Mendelian cancer syndromes. Curr Opin Genet Dev 20: 299–307. S0959-437X(10)00044-4 [pii];10.1016/j.gde.2010.03.010 [doi]. 3...AWARD NUMBER: W81XWH-10-1-0341 TITLE: Genetic Modifiers of Ovarian Cancer PRINCIPAL INVESTIGATOR: Fergus J. Couch, Ph.D. CONTRACTING...DATE AUG 2014 2. REPORT TYPE Final 3. DATES COVERED 15MAY2010 - 14MAY2014 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Genetic Modifiers of Ovarian

  4. What Is Ovarian Cancer?

    Science.gov (United States)

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

  5. 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.

  6. What Are the Risk Factors for Ovarian Cancer?

    Science.gov (United States)

    ... and Prevention What Are the Risk Factors for Ovarian Cancer? A risk factor is anything that changes your ... taking both estrogen and progesterone. Family history of ovarian cancer, breast cancer, or colorectal cancer Ovarian cancer can ...

  7. PARP inhibitors in ovarian cancer.

    Science.gov (United States)

    Ledermann, J A

    2016-04-01

    Slow progress in improving the outcome of ovarian cancer with chemotherapy over the last decade has stimulated research into molecularly targeted therapy. Poly(ADP-ribose) polymerase (PARP) inhibitors target DNA repair and are specifically active in cells that have impaired repair of DNA by the homologous recombination (HR) pathway. Cells with mutated BRCA function have HR deficiency (HRD), which is also present in a significant proportion of non-BRCA-mutated ovarian cancer. In the last decade, olaparib, the first and most-investigated oral PARP inhibitor, has undergone phase I-III trials as a single agent, in comparison with and in addition to chemotherapy, and as a maintenance therapy following chemotherapy. The greatest benefit to-date has been in the maintenance setting, prolonging the progression-free survival of high-grade serous ovarian cancer with a BRCA1/2 mutation. In this group of patients, olaparib has received approval as maintenance following chemotherapy from the EMA, and accelerated approval as a single agent in women who have had three or more lines of therapy. Olaparib can be given for a prolonged period with few significant side-effects in most patients. Similar trials with other PARP inhibitors (rucaparib, niraparib and veliparib) are in progress and include non-BRCA-mutated ovarian cancer. Second-generation studies are exploring the combination of PARP inhibitors with anti-angiogenic drugs. PARP inhibitors represent a step change in the management of ovarian cancer. BRCA mutations are the first genotypic predictive markers in ovarian cancer and can be used to select patients who will most likely benefit from PARP inhibitors. BRCA testing is now becoming a routine part of the evaluation of women with ovarian cancer, and tests for HRD are being used to evaluate PARP inhibitors in an extended population of non-BRCA-mutated ovarian cancer. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical

  8. 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

  9. Paraneoplastic thrombocytosis in ovarian cancer.

    Science.gov (United States)

    Stone, Rebecca L; Nick, Alpa M; McNeish, Iain A; Balkwill, Frances; Han, Hee Dong; Bottsford-Miller, Justin; Rupairmoole, Rajesha; Armaiz-Pena, Guillermo N; Pecot, Chad V; Coward, Jermaine; Deavers, Michael T; Vasquez, Hernan G; Urbauer, Diana; Landen, Charles N; Hu, Wei; Gershenson, Hannah; Matsuo, Koji; Shahzad, Mian M K; King, Erin R; Tekedereli, Ibrahim; Ozpolat, Bulent; Ahn, Edward H; Bond, Virginia K; Wang, Rui; Drew, Angela F; Gushiken, Francisca; Lamkin, Donald; Collins, Katherine; DeGeest, Koen; Lutgendorf, Susan K; Chiu, Wah; Lopez-Berestein, Gabriel; Afshar-Kharghan, Vahid; Sood, Anil K

    2012-02-16

    The mechanisms of paraneoplastic thrombocytosis in ovarian cancer and the role that platelets play in abetting cancer growth are unclear. We analyzed clinical data on 619 patients with epithelial ovarian cancer to test associations between platelet counts and disease outcome. Human samples and mouse models of epithelial ovarian cancer were used to explore the underlying mechanisms of paraneoplastic thrombocytosis. The effects of platelets on tumor growth and angiogenesis were ascertained. Thrombocytosis was significantly associated with advanced disease and shortened survival. Plasma levels of thrombopoietin and interleukin-6 were significantly elevated in patients who had thrombocytosis as compared with those who did not. In mouse models, increased hepatic thrombopoietin synthesis in response to tumor-derived interleukin-6 was an underlying mechanism of paraneoplastic thrombocytosis. Tumor-derived interleukin-6 and hepatic thrombopoietin were also linked to thrombocytosis in patients. Silencing thrombopoietin and interleukin-6 abrogated thrombocytosis in tumor-bearing mice. Anti-interleukin-6 antibody treatment significantly reduced platelet counts in tumor-bearing mice and in patients with epithelial ovarian cancer. In addition, neutralizing interleukin-6 significantly enhanced the therapeutic efficacy of paclitaxel in mouse models of epithelial ovarian cancer. The use of an antiplatelet antibody to halve platelet counts in tumor-bearing mice significantly reduced tumor growth and angiogenesis. These findings support the existence of a paracrine circuit wherein increased production of thrombopoietic cytokines in tumor and host tissue leads to paraneoplastic thrombocytosis, which fuels tumor growth. We speculate that countering paraneoplastic thrombocytosis either directly or indirectly by targeting these cytokines may have therapeutic potential. (Funded by the National Cancer Institute and others.).

  10. MUC1 in endometriosis and ovarian cancer.

    Science.gov (United States)

    Vlad, Anda M; Diaconu, Iulia; Gantt, Kira R

    2006-01-01

    Endometriosis is a chronic, debilitating disease, associated with pelvic pain and infertility. Recent epidemiological studies suggest that women with endometriosis are at increased risk for ovarian cancer. Although the causative factors for both endometriosis and ovarian cancer remain largely unknown, several similarities between the proposed etiology of ovarian cancer and the observed pathophysiology of endometriosis have been reported. MUC1 glycoprotein is present in endometriotic lesions and overexpressed in epithelial ovarian tumors. We are currently studying immunity to MUC1 antigen in newly emerging preclinical models for endometriosis and ovarian cancer and exploring the potential for immune therapy/prevention with MUC1 in both diseases.

  11. Can Ovarian Cancer Be Prevented?

    Science.gov (United States)

    ... need to be removed by the time the woman is 35. Some women who have a high risk of ovarian cancer due to BRCA gene mutations feel that having their ovaries and fallopian tubes removed is not right for them. Often doctors recommend that those women ...

  12. 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...

  13. Characterization of the tumor marker muc16 (ca125 expressed by murine ovarian tumor cell lines and identification of a panel of cross-reactive monoclonal antibodies

    Directory of Open Access Journals (Sweden)

    Goodell Cara AR

    2009-06-01

    Full Text Available Abstract Objectives The ovarian tumor marker CA125 is expressed on human MUC16, a cell surface bound mucin that is also shed by proteolytic cleavage. Human MUC16 is overexpressed by ovarian cancer cells. MUC16 facilitates the binding of ovarian tumor cells to mesothelial cells lining the peritoneal cavity. Additionally, MUC16 also is a potent inhibitor of natural killer cell mediated anti-tumor cytotoxic responses. Extensive studies using human as well as murine ovarian tumor cell models are required to clearly define the function of MUC16 in the progression of ovarian tumors. The major objective of this study was to determine if the murine ovarian tumor cells, MOVCAR, express Muc16 and to characterize antibodies that recognize this mucin. Methods RT-PCR analysis was used for detecting the Muc16 message and size exclusion column chromatography for isolating Muc16 produced by MOVCAR cells. Soluble and cell-associated murine Muc16 were analyzed, respectively, by Western blotting and flow cytometry assays using a new panel of antibodies. The presence of N-linked oligosaccharides on murine Muc16 was determined by ConA chromatography. Results We demonstrate that murine Muc16 is expressed by mouse ovarian cancer cells as an ~250 kDa glycoprotein that carries both O-linked and N-linked oligosaccharides. In contrast to human MUC16, the murine ortholog is primarily released from the cells and cannot be detected on the cell surface. Since the released murine Muc16 is not detected by conventional anti-CA125 assays, we have for the first time identified a panel of anti-human MUC16 antibodies that also recognizes the murine counterpart. Conclusion The antibodies identified in this study can be used in future purification of murine Muc16 and exhaustive study of its properties. Furthermore, the initial identification and characterization of murine Muc16 is a vital preliminary step in the development of effective murine models of human ovarian cancer. These

  14. Ovarian cancer: epidemiology and risk factors.

    Science.gov (United States)

    La Vecchia, Carlo

    2017-01-01

    The present overview of ovarian cancer epidemiology summarizes the main results for a network of case-control studies in Italy and from the Collaborative Group on Epidemiological Studies of Ovarian Cancer. There are consistent inverse relations between parity, oral contraceptive use and the risk of ovarian cancer. For other menstrual and hormonal factors (i.e. early age at menarche and late menopause), there are established associations, but of limited impact on ovarian cancer incidence on a population level. Serous and endometrioid ovarian cancers (but not mucinous or clear cell types) are related to current and recent use of hormone replacement therapy in menopause. There are no strong associations with alcohol and tobacco overall, but a direct link for tobacco with (borderline) mucinous cancers, of limited impact, however, on overall ovarian cancer mortality. There are direct associations of ovarian cancer risk with height and BMI, as well as possible relations with selected dietary factors - in the absence, however, of consistent findings - and a possible inverse association with physical activity. There is a strong association with a family history of ovarian cancer (and a few selected other neoplasms, including colorectum and endometrium). Recognized risk factors explain only a limited proportion of ovarian cancer cases on a population level. A key reason for the recent favourable trends of ovarian cancer incidence and mortality in several high-income countries is the widespread use of oral contraceptive in the generations born after 1930.

  15. Rucaparib Approved for Ovarian Cancer.

    Science.gov (United States)

    2017-02-01

    The FDA approved the PARP inhibitor rucaparib to treat women with advanced ovarian cancer who have already been treated with at least two chemotherapies and have a BRCA1 or BRCA2 gene mutation identified by an approved companion diagnostic test. The agency also gave a nod to the FoundationFocus CDxBRCA test to detect BRCA alterations. ©2017 American Association for Cancer Research.

  16. Ovarian and tubal cancer in Denmark

    DEFF Research Database (Denmark)

    Gottschau, Mathilde; Mellemkjaer, Lene; Hannibal, Charlotte G

    2016-01-01

    INTRODUCTION: The Nordic countries are areas with a high-incidence of ovarian cancer; however, differences between the countries exist. MATERIAL AND METHODS: We used the Danish Cancer Registry to identify 11 264 cases of ovarian cancer and 363 cases of tubal cancer during 1993-2013. We calculated...

  17. Proton-sensing ovarian cancer G protein-coupled receptor 1 on dendritic cells is required for airway responses in a murine asthma model.

    Science.gov (United States)

    Aoki, Haruka; Mogi, Chihiro; Hisada, Takeshi; Nakakura, Takashi; Kamide, Yosuke; Ichimonji, Isao; Tomura, Hideaki; Tobo, Masayuki; Sato, Koichi; Tsurumaki, Hiroaki; Dobashi, Kunio; Mori, Tetsuya; Harada, Akihiro; Yamada, Masanobu; Mori, Masatomo; Ishizuka, Tamotsu; Okajima, Fumikazu

    2013-01-01

    Ovarian cancer G protein-coupled receptor 1 (OGR1) stimulation by extracellular protons causes the activation of G proteins and subsequent cellular functions. However, the physiological and pathophysiological roles of OGR1 in airway responses remain largely unknown. In the present study, we show that OGR1-deficient mice are resistant to the cardinal features of asthma, including airway eosinophilia, airway hyperresponsiveness (AHR), and goblet cell metaplasia, in association with a remarkable inhibition of Th2 cytokine and IgE production, in an ovalbumin (OVA)-induced asthma model. Intratracheal transfer to wild-type mice of OVA-primed bone marrow-derived dendritic cells (DCs) from OGR1-deficient mice developed lower AHR and eosinophilia after OVA inhalation compared with the transfer of those from wild-type mice. Migration of OVA-pulsed DCs to peribronchial lymph nodes was also inhibited by OGR1 deficiency in the adoption experiments. The presence of functional OGR1 in DCs was confirmed by the expression of OGR1 mRNA and the OGR1-sensitive Ca(2+) response. OVA-induced expression of CCR7, a mature DC chemokine receptor, and migration response to CCR7 ligands in an in vitro Transwell assay were attenuated by OGR1 deficiency. We conclude that OGR1 on DCs is critical for migration to draining lymph nodes, which, in turn, stimulates Th2 phenotype change and subsequent induction of airway inflammation and AHR.

  18. Risks of Ovarian, Fallopian Tube, and Primary Peritoneal Cancer Screening

    Science.gov (United States)

    ... Screening Research Ovarian, Fallopian Tube, and Primary Peritoneal Cancer Screening (PDQ®)–Patient Version What is screening? Go to ... ovarian cancer. Ovarian, Fallopian Tube, and Primary Peritoneal Cancer Screening Key Points Tests are used to screen for ...

  19. Ovarian, Fallopian Tube, and Primary Peritoneal Cancer Screening

    Science.gov (United States)

    ... Screening Research Ovarian, Fallopian Tube, and Primary Peritoneal Cancer Screening (PDQ®)–Patient Version What is screening? Go to ... ovarian cancer. Ovarian, Fallopian Tube, and Primary Peritoneal Cancer Screening Key Points Tests are used to screen for ...

  20. 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...

  1. 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.

  2. Platelet effects on ovarian cancer

    Science.gov (United States)

    Davis, Ashley; Afshar-Kharghan, Vahid; Sood, Anil K.

    2014-01-01

    Growing understanding of the role of thrombocytosis, high platelet turnover, and the presence of activated platelets in the circulation in cancer progression and metastasis has brought megakaryocytes into focus. Platelet biology is essential to hemostasis, vascular integrity, angiogenesis, inflammation, innate immunity, wound healing, and cancer biology. However, before megakaryocyte/platelet-directed therapies can be considered for clinical use, understanding of the mechanism and biology of paraneoplastic thrombocytosis in malignancy is required. Here, we provide an overview of the clinical implications, biological significance, and mechanisms of paraneoplastic thrombocytosis in the context of ovarian cancer. PMID:25023353

  3. Pelvic Inflammatory Disease and the Risk of Ovarian Cancer and Borderline Ovarian Tumors

    DEFF Research Database (Denmark)

    Rasmussen, Christina B; Kjaer, Susanne K; Albieri, Vanna

    2017-01-01

    Inflammation has been implicated in ovarian carcinogenesis. However, studies investigating the association between pelvic inflammatory disease (PID) and ovarian cancer risk are few and inconsistent. We investigated the association between PID and the risk of epithelial ovarian cancer according...

  4. Estrogen biosynthesis and action in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Theresia eThalhammer

    2014-11-01

    Full Text Available Ovarian cancer is still the deadliest of all gynecologic malignancies in women worldwide. This is attributed to two main features of these tumors, namely, i a diagnosis at an advanced tumor stage, and, ii the rapid onset of resistance to standard chemotherapy after an initial successful therapy with platin- and taxol-derivatives. Therefore, novel targets for an early diagnosis and better treatment options for these tumors are urgently needed. Epidemiological data show that induction and biology of ovarian cancer is related to life-time estrogen exposure. Also experimental data reveal that ovarian cancer cells share a number of estrogen regulated pathways with other hormone-dependent cancers, e.g. breast and endometrial cancer. However, ovarian cancer is a heterogeneous disease and the subtypes are quite different with respect to mutations, origins, behaviours, markers and prognosis and respond differently to standard chemotherapy. Therefore, a characterization of ovarian cancer subtypes may lead to better treatment options for the various subtypes and in particular for the most frequently observed high-grade serous ovarian carcinoma. For this intention, further studies on estrogen-related pathways and estrogen formation in ovarian cancer cells are warranted. The review gives an overview on ovarian cancer subtypes and explains the role of estrogen in ovarian cancer. Furthermore, enzymes active to synthesize and metabolize estrogens are described and strategies to target these pathways are discussed.

  5. 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

  6. 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...

  7. 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...... that HBOC and HNPCC associated ovarian cancer develop along distinct genetic pathways and genetic profiles can thus be applied to distinguish between different types of hereditary ovarian cancer....

  8. Hereditary breast and ovarian cancer

    DEFF Research Database (Denmark)

    Nielsen, Finn Cilius; Hansen, Thomas van Overeem; 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...... affected families without BRCA1 or BRCA2 mutations. The new pathogenic variants are rare, posing challenges to estimation of risk attribution through patient cohorts. In this Review article, we examine HBOC genes, focusing on their role in genome maintenance, the possibilities for functional testing...... of putative causal variants and the clinical application of new HBOC genes in cancer risk management and treatment decision-making....

  9. Rethinking Ovarian Cancer: Recommendations for Improving Outcomes

    OpenAIRE

    2011-01-01

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

  10. 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....

  11. General Information about Ovarian Epithelial Cancer

    Science.gov (United States)

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

  12. Radiation treatment of ovarian cancer

    Energy Technology Data Exchange (ETDEWEB)

    Morita, S.; Arai, T.; Kurisu, A. (National Inst. of Radiological Sciences, Chiba (Japan))

    1982-03-01

    We evaluated the clinical results obtained in 129 primary malignant ovarian cancer patients who had been treated by 4 modes of postoperative irradiation between 1961 and 1980 at NIRS. The 3- and 5-year survival rates were 52% (45/86) and 43% (32/75) in total and 71% (20/28) and 59% (10/17) in whole abdominal irradiation cases, respectively. Leucopenia (>2,000) occurred in 48%, ileus in 5.2% of the latter cases. The necessity of combining radiation therapy with surgery and chemotherapy was emphasized.

  13. Identification of BRCA1-deficient ovarian cancers

    DEFF Research Database (Denmark)

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

    2011-01-01

    Objective. It is believed that 24 - 40% of ovarian cancers have dysfunction in the BRCA1 or BRCA2 (BRCAness) genes, either due to inherited or somatic mutations or due to epigenetic inactivation. Demonstration of ovarian cancers with BRCAness is becoming important both due to the possibility...... of offering genetic counseling and due to beneficial effects of PARP inhibitor treatment in this group. Since DNA sequencing is expensive and time-consuming efforts have been devoted to develop more indirect methods for BRCA screening that can improve the selection of patients for sequence-based BRCA testing....... 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...

  14. 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.

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

    DEFF Research Database (Denmark)

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

    2009-01-01

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

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

    DEFF Research Database (Denmark)

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

    2009-01-01

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

  17. [Update on current care guidelines: ovarian cancer].

    Science.gov (United States)

    Leminen, Arto; Auranen, Annika; Bützow, Ralf; Hietanen, Sakari; Komulainen, Marja; Kuoppala, Tapio; Mäenpää, Johanna; Puistola, Ulla; Vuento, Maarit; Vuorela, Piia; Yliskoski, Merja

    2012-01-01

    Ovarian cancer is the most lethal gynaecological cancer. It appears that seemingly ovarian or primary peritoneal carcinomas, in fact, originate from fimbriae. BRCA1/2 mutation carriers are recommended for the removal of ovaries and fimbriae, to reduce the risk of cancer. Treatment of epithelial ovarian cancer is based on the combination of surgery and chemotherapy. The residual tumour volume at the primary operation is the most important predictive factor of survival. The best response at the primary treatment is observed with combination chemotherapy with taxane and platinum. Adding bevacitzumab to first line chemotherapy may improve survival.

  18. Ovarian cancer gene therapy using HPV-16 pseudovirion carrying the HSV-tk gene.

    Directory of Open Access Journals (Sweden)

    Chien-Fu Hung

    Full Text Available Ovarian cancer is the leading cause of death from all gynecological cancers and conventional therapies such as surgery, chemotherapy, and radiotherapy usually fail to control advanced stages of the disease. Thus, there is an urgent need for alternative and innovative therapeutic options. We reason that cancer gene therapy using a vector capable of specifically delivering an enzyme-encoding gene to ovarian cancer cells will allow the cancer cell to metabolize a harmless prodrug into a potent cytotoxin, which will lead to therapeutic effects. In the current study, we explore the use of a human papillomavirus (HPV pseudovirion to deliver a herpes simplex virus thymidine kinase (HSV-tk gene to ovarian tumor cells. We found that the HPV-16 pseudovirion was able to preferentially infect murine and human ovarian tumor cells when administered intraperitoneally. Furthermore, intraperitoneal injection of HPV-16 pseudovirions carrying the HSV-tk gene followed by treatment with ganciclovir led to significant therapeutic anti-tumor effects in murine ovarian cancer-bearing mice. Our data suggest that HPV pseudovirion may serve as a potential delivery vehicle for ovarian cancer gene therapy.

  19. Hormone therapy and different ovarian cancers

    DEFF Research Database (Denmark)

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

    2012-01-01

    , 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......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...

  20. 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...

  1. Emerging treatments for ovarian cancer.

    Science.gov (United States)

    Muggia, Franco; Lu, M Janice

    2003-05-01

    The survival at 5 years, of patients with ovarian cancer, has steadily improved since 1960, when surgery and alkylating agents were the only initial modalities employed to cope with the usual late presentation of the disease. In the 1980s, cisplatin and then carboplatin became established as the most active drugs, alone or in combination with other drugs. In the last decade, the antimicrotubulin drug paclitaxel, and the topoisomerase I inhibitor topotecan were noted to be active after failure of platinum drugs. These drugs, as well as others with known activity in the second-line setting, such as the pegylated liposomal doxorubicin, gemcitabine and oral etoposide, all play a role in the treatment of these patients and likely prolong survival without eradicating the disease. The plight of these patients has stimulated new areas of drug development. Here, the evolution of the current therapeutic strategy, the scientific rationale for cytotoxic and non-cytotoxic agents and their status at present are reviewed. 'Targeted' drug trials, in contrast to trials studying cytotoxic drug analogues, currently represent only a minor portion of clinical trials in ovarian cancer.

  2. 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....

  3. Imminent ovarian failure in childhood cancer survivors

    NARCIS (Netherlands)

    Lantinga, G. M.; Simons, A. H. M.; Kamps, W. A.; Postma, A.

    2006-01-01

    The aim of this study was to investigate reproductive history and the prevalence of imminent ovarian failure (IOF) in female childhood cancer survivors. Reproductive history and ovarian function were evaluated by questionnaires (n = 124) and by measurement of follicle stimulating hormone (FSH) and o

  4. 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....

  5. 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

  6. 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.  ...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-07-18

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

  8. COMPARISON OF FOUR METHODS TO GENERATE IMMUNOREACTIVE FRAGMENTS OF A MURINE MONOCLONAL ANTIBODY OC859 AGAINST HUMAN OVARIAN EPITHELIAL CANCER ANTIGEN

    Institute of Scientific and Technical Information of China (English)

    邹颖; 卞美璐; 杨子义; 连利娟; 刘文淑; 许秀英

    1995-01-01

    In the present study,four different proteases (pepsin,papain,bromelain and ficin) were screened with a murine monoclonal antibody OC859,in order to verify whether different digestion procedures could improve yield and stability of the F(ab')2 or Fab fragments.The yields of F(ab')2 or Fab fragments from digestion with pepsin,papain,bromelain and ficin were respectively 20.3+/-2.0%,50.5%+/-5.0%,74.4+/-2.7% and 82.8+/-10.2% of the theoretical maximum.Immunoreactivity in a noncompetitive solid-phase radioimmunoassay (SPRIA) of the fragments generated by the four proteases were respectively 10+/-5%,36+/-5%,60+/-6% and 75+/-6% of the intact OC859 IgG.These results suggested that the fragmentation of OC859 with ficin gave a higher yield of superior immunoreactive fragments.

  9. 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......  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...... 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.  ...

  10. 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 improved......-grade serous invasive tumours (1.13, 1.03–1.25) and in pre-menopausal women (1.11; 1.04–1.18). Among post-menopausal women, the associations did not differ between hormone replacement therapy users and non-users. Whilst obesity appears to increase risk of the less common histological subtypes of ovarian cancer......, 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....

  11. Genetic and molecular changes in ovarian cancer

    Institute of Scientific and Technical Information of China (English)

    Robert L Hollis; Charlie Gourley

    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.

  12. IL-6 Receptor Isoforms and Ovarian Cancer

    Science.gov (United States)

    2013-01-01

    11. Robinson-Smith TM et al (2007) Macrophages mediate inflam - mation-enhanced metastasis of ovarian tumors in mice. Cancer Res 67(12):5708–5716 12...granulation tissue contains many of the inflam - matory cell types, cytokines, and angiogenic vessels typical of inflammation. Deficits in macrophage ...immune cells, has been shown to be a preferred site of metastatic dissemination in ovarian cancer patients. Immune cells such as macrophages and

  13. Prognostic factors in young ovarian cancer patients

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  14. Symptoms Relevant to Surveillance for Ovarian Cancer.

    Science.gov (United States)

    Ore, Robert M; Baldwin, Lauren; Woolum, Dylan; Elliott, Erika; Wijers, Christiaan; Chen, Chieh-Yu; Miller, Rachel W; DeSimone, Christopher P; Ueland, Frederick R; Kryscio, Richard J; Nagell, John R van; Pavlik, Edward J

    2017-03-20

    To examine how frequently and confidently healthy women report symptoms during surveillance for ovarian cancer. A symptoms questionnaire was administered to 24,526 women over multiple visits accounting for 70,734 reports. A query of reported confidence was included as a confidence score (CS). Chi square, McNemars test, ANOVA and multivariate analyses were performed. 17,623 women completed the symptoms questionnaire more than one time and >9500 women completed it more than one four times for >43,000 serially completed questionnaires. Reporting ovarian cancer symptoms was ~245 higher than ovarian cancer incidence. The positive predictive value (0.073%) for identifying ovarian cancer based on symptoms alone would predict one malignancy for 1368 cases taken to surgery due to reported symptoms. Confidence on the first questionnaire (83.3%) decreased to 74% when more than five questionnaires were completed. Age-related decreases in confidence were significant (p replacement therapy or abnormal ultrasound findings (p = 0.30 and 0.89). The frequency of symptoms relevant to ovarian cancer was much higher than the occurrence of ovarian cancer. Approximately 80.1% of women expressed confidence in what they reported.

  15. Symptoms Relevant to Surveillance for Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Robert M. Ore

    2017-03-01

    Full Text Available To examine how frequently and confidently healthy women report symptoms during surveillance for ovarian cancer. A symptoms questionnaire was administered to 24,526 women over multiple visits accounting for 70,734 reports. A query of reported confidence was included as a confidence score (CS. Chi square, McNemars test, ANOVA and multivariate analyses were performed. 17,623 women completed the symptoms questionnaire more than one time and >9500 women completed it more than one four times for >43,000 serially completed questionnaires. Reporting ovarian cancer symptoms was ~245 higher than ovarian cancer incidence. The positive predictive value (0.073% for identifying ovarian cancer based on symptoms alone would predict one malignancy for 1368 cases taken to surgery due to reported symptoms. Confidence on the first questionnaire (83.3% decreased to 74% when more than five questionnaires were completed. Age-related decreases in confidence were significant (p < 0.0001. Women reporting at least one symptom expressed more confidence (41,984/52,379 = 80.2% than women reporting no symptoms (11,882/18,355 = 64.7%, p < 0.0001. Confidence was unrelated to history of hormone replacement therapy or abnormal ultrasound findings (p = 0.30 and 0.89. The frequency of symptoms relevant to ovarian cancer was much higher than the occurrence of ovarian cancer. Approximately 80.1% of women expressed confidence in what they reported.

  16. 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.

  17. Approaches to the detection of ovarian cancer

    DEFF Research Database (Denmark)

    Høgdall, Estrid

    2016-01-01

    of patients with OC. Approaches to detect OC may be based on a gynecological examination, an elevated serum CA125 level, a Risk of Malignancy Index (RMI) higher than 200, an elevated serum HE4 level, or other modalities such as Risk of Ovarian Malignancy Algorithm (ROMA), Risk of Ovarian Cancer Algorithm......BACKGROUND: Ovarian cancer (OC) represents the eighth most common cancer among women and the second most frequently diagnosed gynecological malignancy in the United States and Europe. Correct and fast referral of patients with OC is mandatory to ensure optimal treatment and to improve the prognosis...... (ROCA), or Copenhagen Index (CPH-I). AIM: To describe biomarkers that potentially improve the detection/risk estimation of OC. RESULTS: The ability to differentiate OC from benign and borderline ovarian tumors was analyzed using Receiver Operating Characteristics (ROC) curves resulting in Area Under...

  18. HE4 Gene Overexpression in Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    A Shahi

    2016-03-01

    Full Text Available Introduction: Ovarian cancer is one of the common malignancies within women and the fifth cause of cancer death in women all over the world. Recent developments in Genomics and Proteomics technologies have led to the identification of unknown candidate markers for the diagnosis of ovarian cancer. Human epididymis protein 4 (HE4 has recently been supported to monitor the recurrence or the progression of epithelial ovarian cancer. Therefore, this study aimed to measure the expression of HE4 in women suffering from ovarian cancer. Methods: In this study, 20 paraffin-embedded tissue samples from women with ovarian cancer and 10 normal samples were collected from Imam Khomeini Hospital in Tehran. After removing paraffin, RNA extraction was performed with RNAPlus solution. cDNA was synthesized through reverse transcription by MMULV enzyme. Gene expression was measured by Relative Real time PCR method. Glyceraldehyde phosphate dehydrogenase gene (GAPDH was used as an internal control. Results: The HE4 was expressed in normal and cancerous tissues, though its expression was observed more in tumor tissues (4.083 than noncancerous tissues. The study results also revealed that the expression level of HE4 increased with the advancement of the disease. Conclusion: According to the results, it can be concluded that HE4 expression levels greatly increases in tumor samples. Therefore, HE4 gene expression measurements can serve as a valuable prognostic factor for early detection and treatment management of the disease.

  19. Identifying alemtuzumab as an anti-myeloid cell antiangiogenic therapy for the treatment of ovarian cancer

    Directory of Open Access Journals (Sweden)

    Coukos George

    2009-06-01

    Full Text Available Abstract Background Murine studies suggest that myeloid cells such as vascular leukocytes (VLC and Tie2+ monocytes play a critical role in tumor angiogenesis and vasculogenesis. Myeloid cells are a primary cause of resistance to anti-VEGF therapy. The elimination of these cells from the tumor microenvironment significantly restricts tumor growth in both spontaneous and xenograft murine tumor models. Thus animal studies indicate that myeloid cells are potential therapeutic targets for solid tumor therapy. Abundant VLC and Tie2+ monocytes have been reported in human cancer. Unfortunately, the importance of VLC in human cancer growth remains untested as there are no confirmed therapeutics to target human VLC. Methods We used FACS to analyze VLC in ovarian and non-ovarian tumors, and characterize the relationship of VLC and Tie2-monocytes. We performed qRT-PCR and FACS on human VLC to assess the expression of the CD52 antigen, the target of the immunotherapeutic Alemtuzumab. We assessed Alemtuzumab's ability to induce complement-mediated VLC killing in vitro and in human tumor ascites. Finally we assessed the impact of anti-CD52 immuno-toxin therapy on murine ovarian tumor growth. Results Human VLC are present in ovarian and non-ovarian tumors. The majority of VLC appear to be Tie2+ monocytes. VLC and Tie2+ monocytes express high levels of CD52, the target of the immunotherapeutic Alemtuzumab. Alemtuzumab potently induces complement-mediated lysis of VLC in vitro and ex-vivo in ovarian tumor ascites. Anti-CD52 immunotherapy targeting VLC restricts tumor angiogenesis and growth in murine ovarian cancer. Conclusion These studies confirm VLC/myeloid cells as therapeutic targets in ovarian cancer. Our data provide critical pre-clinical evidence supporting the use of Alemtuzumab in clinical trials to test its efficacy as an anti-myeloid cell antiangiogenic therapeutic in ovarian cancer. The identification of an FDA approved anti-VLC agent with a history

  20. 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

  1. Colon resection for ovarian cancer: intraoperative decisions.

    Science.gov (United States)

    Hoffman, Mitchel S; Zervose, Emmanuel

    2008-11-01

    To discuss the benefits and morbidity of and indications for colon resection during cytoreductive operations for ovarian cancer. The history of cytoreductive surgery for ovarian cancer is discussed, with special attention to the incorporation of colon resection. Literature regarding cytoreductive surgery for ovarian cancer is then reviewed, again with attention to the role of colon resection. The focus of the review is directed at broad technical considerations and rationales, for both primary and secondary cytoreduction. Over the past 15 to 20 years the standard cytoreductive operation for ovarian cancer has shifted from an abdominal hysterectomy with bilateral salpingo-oophorectomy and omentectomy to an en bloc radical resection of the pelvic tumor and an omentectomy, and more recently to include increasing use of extensive upper abdominal surgery. En bloc pelvic resection frequently includes rectosigmoid resection, almost always accompanied by a primary anastomosis. Other portions of the colon are at risk for metastatic involvement and sometimes require resection in order to achieve optimal cytoreduction. The data regarding colon resection for the purpose of surgical cytoreduction of ovarian cancer are conflicting (in terms of benefit) and all retrospective. However, the preponderance of information supports a benefit in terms of survival when cytoreduction is clearly optimal. Similar to primary surgery, benefit from secondary cytoreduction of ovarian cancer occurs when only a small volume of disease is left behind. The preponderance of data suggests that colon resection to achieve optimal cytoreduction has a positive impact on survival. In order to better understand the role of colon resection as well as other extensive cytoreductive procedures for ovarian cancer, it will be important to continue to improve our understanding of prognostic variables such as the nuances of metastatic bowel involvement in order to better guide appropriate surgical management.

  2. 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....

  3. 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....

  4. Know the Risks, Warning Signs of Ovarian Cancer

    Science.gov (United States)

    ... 163117.html Know the Risks, Warning Signs of Ovarian Cancer Older age, family history raise the odds for ... Women need to be aware their risk for ovarian cancer increases with age. Half of all cases affect ...

  5. Most Women Should Forgo Ovarian Cancer Screening: Panel

    Science.gov (United States)

    ... fullstory_167271.html Most Women Should Forgo Ovarian Cancer Screening: Panel Test isn't accurate enough to justify ... 2017 (HealthDay News) -- The potential harms of ovarian cancer screening outweigh the benefits, so only very specific groups ...

  6. Does Breast or Ovarian Cancer Run in Your Family?

    Science.gov (United States)

    ... Does Breast or Ovarian Cancer Run in Your Family? Language: English Español (Spanish) Recommend on Facebook Tweet ... get ovarian cancer by age 70. Does Your Family Health History Put You At Risk? Collect your ...

  7. Ovarian cancer treatment: The end of empiricism?

    Science.gov (United States)

    Lheureux, Stephanie; Karakasis, Katherine; Kohn, Elise C; Oza, Amit M

    2015-09-15

    The diagnosis, investigation, and management of ovarian cancer are in a state of flux-balancing ever rapid advances in our understanding of its biology with 3 decades of clinical trials. Clinical trials that started with empirically driven selections have evolved in an evidence-informed manner to gradually improve outcome. Has this improved understanding of the biology and associated calls to action led to appropriate changes in therapy? In this review, the authors discuss incorporating emerging data on biology, combinations, dose, and scheduling of new and existing agents with patient preferences in the management of women with ovarian cancer. © 2015 The Authors. American Cancer Society.

  8. 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.

  9. 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.

  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. 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.

  12. Tumor infiltrating lymphocytes in ovarian cancer.

    Science.gov (United States)

    Santoiemma, Phillip P; Powell, Daniel J

    2015-01-01

    The accumulation of tumor infiltrating lymphocytes (TILs) in ovarian cancer is prognostic for increased survival while increases in immunosuppressive regulatory T-cells (Tregs) are associated with poor outcomes. Approaches that bolster tumor-reactive TILs may limit tumor progression. However, identifying tumor-reactive TILs in ovarian cancer has been challenging, though adoptive TIL therapy in patients has been encouraging. Other forms of TIL immunomodulation remain under investigation including Treg depletion, antibody-based checkpoint modification, activation and amplification using dendritic cells, antigen presenting cells or IL-2 cytokine culture, adjuvant cytokine injections, and gene-engineered T-cells. Many approaches to TIL manipulation inhibit ovarian cancer progression in preclinical or clinical studies as monotherapy. Here, we review the impact of TILs in ovarian cancer and attempts to mobilize TILs to halt tumor progression. We conclude that effective TIL therapy for ovarian cancer is at the brink of translation and optimal TIL activity may require combined methodologies to deliver clinically-relevant treatment.

  13. 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

  14. 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

    : Nationwide register-based case-control study. SETTING: Denmark during 1982-2011. POPULATION: Cases were all Danish women diagnosed with epithelial ovarian cancer (n = 13 241) or borderline ovarian tumor (n = 3605) in the study period. Age-matched female population controls were randomly selected by risk set......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...

  15. Ovarian stromal hyperplasia and ovarian vein steroid levels in relation to endometrioid endometrial cancer

    NARCIS (Netherlands)

    Jongen, VHWM; Hollema, H; van der Zee, AGJ; Santema, JG; Heineman, MJ

    2003-01-01

    Objective To study the relationship between the presence of endometrioid endometrial cancer, the degree of ovarian stromal hyperplasia and ovarian steroid production in postmenopausal women. Design Retrospective and prospective study, respectively. Setting Medical Centre Leeuwarden and the Universit

  16. 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.

  17. Pegylated liposomal doxorubicin in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Robert Strother

    2009-08-01

    Full Text Available Robert Strother1,2, Daniela Matei1–51Department of Medicine, 2Indiana University Melvin and Bren Simon Cancer Center, 3Department of Obstetrics and Gynecology, 4Department of Biochemistry and Molecular Biology, 5VA Roudebush Hospital Indiana University School of Medicine, 535 Barnhill Drive, Indianapolis, IN, 46202Abstract: The encapsulation of doxorubicin in a pegylated liposomal matrix led to a reformulated agent with a different toxicity profile and improved clinical utility. Liposomal doxorubicin is devoid of the cardiac toxicity associated with doxorubicin, but is associated with predictable muco-cutaneous toxicity. The liposomal formulation leads to improved delivery to the target tumor tissue, allowing enhanced uptake by cancer cells. These properties translate into clinical utility in recurrent ovarian cancer as demonstrated by phase II and III trials, this proven clinical efficacy leading to FDA approval in second-line therapy for ovarian cancer. New combinations with cytotoxics, in particular with carboplatin, have demonstrated an acceptable toxicity profile and clinical utility in platinum-sensitive ovarian cancer. A favorable toxicity profile renders liposomal doxorubicin an ideal partner for combination regimens with other cytotoxics, and more recently with biological agents. Such combinations are the subject of ongoing clinical trials.Keywords: ovarian cancer, doxorubicin, liposomes, pegylated liposomal doxorubicin

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

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

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

  19. Regulatory T Cells in Human Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Dong-Jun Peng

    2012-01-01

    Full Text Available Multiple layers of suppressive components including regulatory T (TReg cells, suppressive antigen-presenting cells, and inhibitory cytokines form suppressive networks in the ovarian cancer microenvironment. It has been demonstrated that as a major suppressive element, TReg cells infiltrate tumor, interact with several types of immune cells, and mediate immune suppression through different molecular and cellular mechanisms. In this paper, we focus on human ovarian cancer and will discuss the nature of TReg cells including their subsets, trafficking, expansion, and function. We will briefly review the development of manipulation of TReg cells in preclinical and clinical settings.

  20. A Link between mir-100 and FRAP1/mTOR in Clear Cell Ovarian Cancer

    Science.gov (United States)

    Nagaraja, Ankur K.; Creighton, Chad J.; Yu, Zhifeng; Zhu, Huifeng; Gunaratne, Preethi H.; Reid, Jeffrey G.; Olokpa, Emuejevoke; Itamochi, Hiroaki; Ueno, Naoto T.; Hawkins, Shannon M.; Anderson, Matthew L.; Matzuk, Martin M.

    2010-01-01

    MicroRNAs (miRNAs) are small noncoding RNAs that direct gene regulation through translational repression and degradation of complementary mRNA. Although miRNAs have been implicated as oncogenes and tumor suppressors in a variety of human cancers, functional roles for individual miRNAs have not been described in clear cell ovarian carcinoma, an aggressive and chemoresistant subtype of ovarian cancer. We performed deep sequencing to comprehensively profile miRNA expression in 10 human clear cell ovarian cancer cell lines compared with normal ovarian surface epithelial cultures and discovered 54 miRNAs that were aberrantly expressed. Because of the critical roles of the phosphatidylinositol 3-kinase/v-akt murine thymoma viral oncogene homolog 1/mammalian target of rapamycin (mTOR) pathway in clear cell ovarian cancer, we focused on mir-100, a putative tumor suppressor that was the most down-regulated miRNA in our cancer cell lines, and its up-regulated target, FRAP1/mTOR. Overexpression of mir-100 inhibited mTOR signaling and enhanced sensitivity to the rapamycin analog RAD001 (everolimus), confirming the key relationship between mir-100 and the mTOR pathway. Furthermore, overexpression of the putative tumor suppressor mir-22 repressed the EVI1 oncogene, which is known to suppress apoptosis by stimulating phosphatidylinositol 3-kinase/v-akt murine thymoma viral oncogene homolog 1 signaling. In addition to these specific effects, reversing the expression of mir-22 and the putative oncogene mir-182 had widespread effects on target and nontarget gene populations that ultimately caused a global shift in the cancer gene signature toward a more normal state. Our experiments have revealed strong candidate miRNAs and their target genes that may contribute to the pathogenesis of clear cell ovarian cancer, thereby highlighting alternative therapeutic strategies for the treatment of this deadly cancer. PMID:20081105

  1. Survival of ovarian cancer patients in Denmark

    DEFF Research Database (Denmark)

    Edwards, Hellen McKinnon; Noer, Mette Calundann; Sperling, Cecilie Dyg;

    2016-01-01

    BACKGROUND: Ovarian cancer has a high mortality rate, especially in Denmark where mortality rates have been reported higher than in adjacent countries with similar demographics. This study therefore examined recent survival and mortality among Danish ovarian cancer patients over an 18-year study...... period. METHODS: This nationwide registry-based observational study used data from the Danish Gynecology Cancer Database, Danish Pathology Registry, and Danish National Patient Registry. All patients with ovarian cancer diagnosed between 1995 and 2012 were included in the study. The data sources were...... identified 9972 patients diagnosed with ovarian cancer in the period 1995-2012. The absolute one-year mortality rate decreased from 42.8 (CI 40.3-45.6) in 1995-1999 to 28.3 (CI 25.9-30.9) in 2010-2012, and the five-year mortality rate decreased from 28.2 (CI 27.0-29.5) in 1995-1999 to 23.9 (CI 22...

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

    Science.gov (United States)

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

    2008-12-01

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

  3. 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...

  4. Ovarian Cancer, Stem Cells, and Bioreactors

    Science.gov (United States)

    2009-10-01

    produced by the tumor cells and released in the blood stream. CEA serum level is a clinical screening test for colon cancer, but some types of ovarian...Development of a hybrid liver support system: a review. Int J Artif Organs 19, 645-654 (1996). 12. Kusumbe, A.P., Mali, A.M. & Bapat, S.A. CD133-Expressing

  5. 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...

  6. Microvesicles as Potential Ovarian Cancer Biomarkers

    Directory of Open Access Journals (Sweden)

    Ilaria Giusti

    2013-01-01

    Full Text Available Although the incidence of ovarian cancer is low (i.e., less than 5% in European countries, it is the most lethal gynecologic malignancy and typically has a poor prognosis. To ensure optimal survival, it is important to diagnose this condition when the pathology is confined to the ovary. However, this is difficult to achieve because the first specific symptoms appear only during advanced disease stages. To date, the biomarker mainly used for the diagnosis and prognosis of ovarian cancer is CA125; however, this marker has a low sensitivity and specificity and is associated with several other physiological and pathological conditions. No other serum ovarian cancer markers appear to be able to replace or complement CA125, and the current challenge is therefore to identify novel markers for the early diagnosis of this disease. For this purpose, studies have focused on the microvesicles (MVs released from tumor cells. MVs may represent an ideal biomarker because they can be easily isolated from blood, and they have particular features (mainly regarding microRNA profiles that strongly correlate with ovarian cancer stage and may be effective for early diagnosis.

  7. 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...

  8. 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.

  9. 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...

  10. Emerging drugs for ovarian cancer.

    Science.gov (United States)

    Kelland, Lloyd R

    2005-05-01

    Because most patients presenting with advanced ovarian cancer are not curable by surgery alone, chemotherapy represents an essential component of treatment. The disease may be considered as chemosensitive, as in around three-quarters of patients major (complete) responses are seen to initial treatment with the platinum-containing drugs cisplatin and carboplatin either used alone or in combination with the taxane, paclitaxel. However, only 15-20% of patients experience long-term remission as tumours often become resistant. The probability of achieving a second response depends on the duration of remission after first-line therapy: if this is 6, and especially if > 12 months (platinum sensitive), responses may be seen in about a quarter of patients, to the same drugs as used first line or to drugs such as pegylated liposomal doxorubicin, topotecan and hexamethylmelamine (all three are approved in this setting by the FDA). Gemcitabine, oral etoposide, docetaxel and oxaliplatin also show some activity either in sequential addition to existing approved of first-line therapy (as with gemcitabine) or as second-line therapy. However, there is an urgent unmet clinical need for new drugs capable of prolonging survival either by increasing long-term remission rates and/or duration as first-line treatment or to improve on outcomes of second-line treatment. Strategies currently being exploited in clinical trials include attempts to deliver more killing selectively to tumours (e.g., intraperitoneal administration of cisplatin or radiolabelled monoclonal antibodies), agents designed to target drug resistance mechanisms (e.g., TLK-286 activated by glutathione transferase), agents targeting proteins/receptors shown to be selectively expressed in the disease (e.g., monoclonal antibodies recognising CA-125 or HER1; small molecules targeting HER1 such as gefitinib) and disrupting established tumour vasculature (e.g., 5,6-dimethyl xanthenone 4-acetic acid). At the pre-clinical level

  11. Management of recurrent epithelial ovarian cancer

    Science.gov (United States)

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

    2014-01-01

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

  12. Ovarian Aging-Like Phenotype in the Hyperandrogenism-Induced Murine Model of Polycystic Ovary

    Directory of Open Access Journals (Sweden)

    Mohammad Amin Rezvanfar

    2014-01-01

    Full Text Available There are prominently similar symptoms, effectors, and commonalities in the majority of characteristics between ovarian aging and polycystic ovarian syndrome (PCOS. Despite the approved role of oxidative stress in the pathogenesis of PCOS and aging, to our knowledge, the link between the PCO(S and aging has not been investigated yet. In this study we investigated the possible exhibition of ovarian aging phenotype in murine model of PCO induced by daily oral administration of letrozole (1 mg/kg body weight for 21 consecutive days in the female Wistar rats. Hyperandrogenization showed irregular cycles and histopathological characteristics of PCO which was associated with a significant increase in lipid peroxidation (LPO and reactive oxygen species (ROS and decrease in total antioxidant capacity (TAC in serum and ovary. Moreover, serum testosterone, insulin and tumor necrosis factor-alpha (TNF-α levels, and ovarian matrix metalloproteinase-2 (MMP-2 were increased in PCO rats compared with healthy controls, while estradiol and progesterone diminished. Almost all of these findings are interestingly found to be common with the characteristics identified with (ovarian aging showing that hyperandrogenism-induced PCO in rat is associated with ovarian aging-like phenotypes. To our knowledge, this is the first report that provides evidence regarding the phenomenon of aging in PCO.

  13. Epidemiology of ovarian cancer: a review

    OpenAIRE

    Reid, Brett M; Permuth, Jennifer B; Sellers, Thomas A.

    2017-01-01

    Ovarian cancer (OC) is the seventh most commonly diagnosed cancer among women in the world and the tenth most common in China. Epithelial OC is the most predominant pathologic subtype, with five major histotypes that differ in origination, pathogenesis, molecular alterations, risk factors, and prognosis. Genetic susceptibility is manifested by rare inherited mutations with high to moderate penetrance. Genome-wide association studies have additionally identified 29 common susceptibility allele...

  14. Genetics Home Reference: ovarian cancer

    Science.gov (United States)

    ... mutations, are not inherited. Somatic mutations in the TP53 gene occur in almost half of all ovarian ... PALB2 PIK3CA PMS2 PRKN RAD50 RAD51C RAD51D STK11 TP53 Related Information What is a gene? What is ...

  15. Glutathione in Preventing Peripheral Neuropathy Caused by Paclitaxel and Carboplatin in Patients With Ovarian Cancer, Fallopian Tube Cancer, and/or Primary Peritoneal Cancer

    Science.gov (United States)

    2017-01-05

    Chemotherapeutic Agent Toxicity; Neuropathy; Neurotoxicity Syndrome; Pain; 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

  16. 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.

  17. 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...... debulking surgery. The aim of this study was to investigate the use of NACT in Denmark in regard to increased use and regional differences. MATERIAL AND METHODS: Stage IIIC and IV ovarian cancer patients treated in the five Danish tertiary referral centres in the 2005-2010-period were included. The study...... is based on validated data from The Danish Gynaecological Cancer Database. RESULTS: Of the 1,367 eligible patients 1,069 were treated with PDS and 298 with NACT. In 2005-2007, 11% of patients were treated with NACT. In 2008-2010, this percentage had risen to 30% (p

  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...... debulking surgery. The aim of this study was to investigate the use of NACT in Denmark in regard to increased use and regional differences. MATERIAL AND METHODS: Stage IIIC and IV ovarian cancer patients treated in the five Danish tertiary referral centres in the 2005-2010-period were included. The study...... is based on validated data from The Danish Gynaecological Cancer Database. RESULTS: Of the 1,367 eligible patients 1,069 were treated with PDS and 298 with NACT. In 2005-2007, 11% of patients were treated with NACT. In 2008-2010, this percentage had risen to 30% (p

  19. Oncogenic pathways implicated in ovarian epithelial cancer.

    Science.gov (United States)

    Nicosia, Santo V; Bai, Wenlong; Cheng, Jin Q; Coppola, Domenico; Kruk, Patricia A

    2003-08-01

    Characterization of intracellular signaling pathways should lead to a better understanding of ovarian epithelial carcinogenesis and provide an opportunity to interfere with signal transduction targets involved in ovarian tumor cell growth, survival, and progression. Challenges toward such an effort are significant because many of these signals are part of cascades within an intricate and likely redundant intracellular signaling network (Fig.1). For instance, a given signal may activate a dual intracellular pathway (ie, MEK1-MAPK and PI3K/Akt required for fibronectin-dependent activation of matrix metalloproteinase 9). A single pathway also may transduce more than one biologic or oncogenic signal (ie, PI3K signaling in epithelial and endothelial cell growth and sprouting of neovessels). Despite these challenges, evidence for therapeutic targeting of signal transduction pathways is accumulating in human cancer. For instance, the EGF-specific tyrosine kinase inhibitor ZD 1839 (Iressa) may have a beneficial therapeutic effect on ovarian epithelial cancer. Therapy of this cancer may include inhibitors of PI kinase (quercetin), ezrin and PIP kinase (genistein). The G protein-coupled family of receptors, including LPA, also is an attractive target to drugs, although their frequent pleiotropic functions may be at times toxic and lack specificity. Because of the lack of notable toxicity, PI3K/Akt pathway inhibitors such as FTIs are a promising targeted therapy of ovarian epithelial cancer. Increasing insight into the oncogenic pathways involved in ovarian epithelial cancer also is helping clinicians to understand better the phenomenon of chemoresistance in this malignancy. Oncogenic activation of gamma-synuclein promotes cell survival and provides resistance to paclitaxel, but such a resistance is partially overcome by an MEK inhibitor that suppresses ERK activity. Ovarian epithelial cancer is a complex group of neoplasms with an overall poor prognosis. Comprehension of

  20. 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.

  1. 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...... in epithelial ovarian cancer. METHODS: Immunohistochemical stainings for ERα, ERβ, PR, and AR were assessed in relation to survival in 118 serous and endometrioid ovarian cancers. Expression of the genes encoding the four receptors was studied in relation to prognosis in the molecular subtypes of ovarian cancer...... in ovarian cancer and support that tumors should be stratified based on molecular as well as histological subtypes in future studies investigating the role of endocrine treatment in ovarian cancer....

  2. 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+ ...

  3. 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...

  4. Use of common analgesic medications and ovarian cancer survival

    DEFF Research Database (Denmark)

    Dixon, Suzanne C; Nagle, Christina M; Wentzensen, Nicolas

    2017-01-01

    BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with improved survival in some cancers, but evidence for ovarian cancer is limited. METHODS: Pooling individual-level data from 12 Ovarian Cancer Association Consortium studies, we evaluated the association between sel...

  5. Targeting the tumour microenvironment in ovarian cancer.

    Science.gov (United States)

    Hansen, Jean M; Coleman, Robert L; Sood, Anil K

    2016-03-01

    The study of cancer initiation, growth, and metastasis has traditionally been focused on cancer cells, and the view that they proliferate due to uncontrolled growth signalling owing to genetic derangements. However, uncontrolled growth in tumours cannot be explained solely by aberrations in cancer cells themselves. To fully understand the biological behaviour of tumours, it is essential to understand the microenvironment in which cancer cells exist, and how they manipulate the surrounding stroma to promote the malignant phenotype. Ovarian cancer is the leading cause of death from gynaecologic cancer worldwide. The majority of patients will have objective responses to standard tumour debulking surgery and platinum-taxane doublet chemotherapy, but most will experience disease recurrence and chemotherapy resistance. As such, a great deal of effort has been put forth to develop therapies that target the tumour microenvironment in ovarian cancer. Herein, we review the key components of the tumour microenvironment as they pertain to this disease, outline targeting opportunities and supporting evidence thus far, and discuss resistance to therapy.

  6. 77 FR 55095 - National Ovarian Cancer Awareness Month, 2012

    Science.gov (United States)

    2012-09-06

    ... their lives to ovarian cancer. They are mothers and daughters, sisters and grandmothers, community... treatments. Through the Centers for Disease Control's Inside Knowledge campaign, we are working to...

  7. 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.

  8. Optimal cytoreduction for advanced epithelial ovarian cancer

    Directory of Open Access Journals (Sweden)

    N. G. Kormosh

    2010-01-01

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

  9. 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.

  10. Transvaginal ultrasonography in ovarian cancer screening: current perspectives

    Directory of Open Access Journals (Sweden)

    van Nagell Jr JR

    2013-12-01

    Full Text Available John R van Nagell Jr, John T HoffDepartment of Obstetrics and Gynecology, University of Kentucky Chandler Medical Center/Markey Cancer Center, Lexington, KY, USAAbstract: Transvaginal ultrasonography (TVS is an integral part of all major ovarian cancer screening trials. TVS is accurate in detecting abnormalities in ovarian volume and morphology, but is less reliable in differentiating benign from malignant ovarian tumors. When used as the only screening test, TVS is sensitive, but has a low positive predictive value. Therefore, serum biomarkers and tumor morphology indexing are used together with TVS to identify ovarian tumors at high risk for malignancy. This allows preoperative triage of high-risk cases to major cancer centers for therapy while decreasing unnecessary surgery for benign disease. Ovarian cancer screening has been associated with a decrease in stage at detection in most trials, thereby allowing treatment to be initiated when the disease is most curable.Keywords: ovarian cancer, ultrasound, screening, serum Ca-125

  11. Epigenetic Characterization of Ovarian Cancer

    Science.gov (United States)

    2008-12-01

    prognostic markers for biochemical recurrence among prostate cancer patients with clinically localized disease. Epigenetics, 2006. 1(4): p. 183-6. 6...32. Zhao, H., et al., CpG methylation at promoter site -140 inactivates TGFbeta2 receptor gene in prostate cancer. Cancer, 2005. 104(1): p. 44-52...5]: taxis GO:0006935 [6]: chemotaxis GO:0001525 [6]: angiogenesis GO:0007155 [4]: cell adhesion GO:0030155 [4]: regulation of cell adhesion GO:0006954

  12. Clinical Use of Cancer Biomarkers in Epithelial Ovarian Cancer

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  13. Deciphering the Adaptive Immune Response to Ovarian Cancer

    Science.gov (United States)

    2015-12-01

    faciliate the development of more effective immunotherapies for ovarian cancer . 15. SUBJECT TERMS Tumor immunology , immunotherapy, ovarian cancer , antibody...findings is under review at the AACR journal Clinical Cancer Research (Appendix A). 1.6 Cloning and production of recombinant IgG from tumor-derived...lymphocytes in cancer : a critical review of the literature. Clin Cancer Res. 2012 Jun 1;18(11):3022-9. doi: 10.1158/1078-0432.CCR-11-3216. Epub 2012 Apr 17

  14. Clinical epidemiology of epithelial ovarian cancer in the UK

    Directory of Open Access Journals (Sweden)

    Doufekas K

    2014-05-01

    Full Text Available Konstantinos Doufekas, Adeola OlaitanDepartment of Gynaecological Oncology, University College London Hospitals, London, UKAbstract: Epithelial ovarian cancer is the fifth commonest cancer among women and the leading cause of gynecological cancer death in the UK. Most women present with advanced disease, mainly because the nonspecific nature of the symptoms lead to diagnostic delays. Recent data have shown a fall in ovarian cancer mortality rates in the UK, but rates are still higher when compared to other European countries or the USA. In addition, surgeons in the UK achieve on average lower optimal surgical cytoreduction rates in patients with advanced ovarian cancer. Despite a wealth of information on epidemiological risk factors, the pathogenesis of epithelial ovarian cancer remains largely unknown. This review presents the most recent data on incidence, mortality, and survival for epithelial ovarian cancer in the UK. Time trends, trends by age, international comparisons, and regional variation in incidence, survival, and mortality are presented within the context of a major reorganization of cancer services that took place in the UK over 10 years ago. Centralization of cancer services has meant that women with ovarian cancer receive treatment in specialist Cancer Centers.Keywords: ovarian, cancer, epidemiology, UK, incidence, survival

  15. 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.

  16. 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.

  17. Ovarian cancer epidemiology in the era of collaborative team science.

    Science.gov (United States)

    Cannioto, Rikki A; Trabert, Britton; Poole, Elizabeth M; Schildkraut, Joellen M

    2017-05-01

    Over the past decade, a number of consortia have formed to further investigate genetic associations, pathogenesis, and epidemiologic risk and prognostic factors for ovarian cancer. Here, we review the benefits that ovarian cancer consortia provide as well as challenges that have arisen. Methods for managing key challenges are also discussed. We review the structural organization and some of the milestone epidemiologic publications of five consortia dedicated to the study of ovarian cancer, including the Ovarian Cancer Association Consortium (OCAC), the Ovarian Tumor Tissue Analysis (OTTA) Consortium, the Ovarian Cancer Cohort Consortium (OC3), the Collaborative Group on Epidemiological Studies of Ovarian Cancer (The Oxford Collaborative Group), and the Ovarian Cancer in Women of African Ancestry (OCWAA) consortium. As ovarian cancer is a rare and heterogeneous disease, consortia have made important contributions in the study of risk factors by improving statistical power beyond what any single study, or even a few studies, would provide. Thus, a major accomplishment of consortial research is enhanced characterization of histotype-specific risk factor associations. In addition, consortia have facilitated impressive synergy between researchers across many institutions, spawning new collaborative research. Importantly, through these efforts, many challenges have been met, including difficulties with data harmonization and analysis, laying a road map for future collaborations. While ovarian cancer consortia have made valuable contributions to the ovarian cancer epidemiological literature over the past decade, additional efforts comprising of new, well-designed case-control studies are needed to further elucidate novel, histotype-specific risk, and prognostic factors which are not consistently available in existing studies.

  18. 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.

  19. Vaccine-based clinical trials in ovarian cancer

    NARCIS (Netherlands)

    Leffers, Ninke; Daemen, Toos; Boezen, H. Marike; Melief, Kees J. M.; Nijman, Hans W.

    2011-01-01

    Ovarian cancer vaccines are one of the new treatment strategies under investigation in epithelial ovarian cancer. This article discusses the results of different immunization strategies, points out potential pitfalls in study designs and provides possible solutions for augmentation of clinical effic

  20. 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. 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. Breast and Ovarian Cancer and Family History Risk Categories

    Science.gov (United States)

    ... NCCN Guidelines Version 2.2014 Genetics/Familial High-Risk Assessment: Breast and Ovarian. MS3-8. Final Recommendation Statement: Breast Cancer: Screening. U.S. Preventive Services Task Force. February 2016. Family Health History, Breast and Ovarian Cancer Risk, and Women ...

  3. Is Pelvic Inflammatory Disease a Risk Factor for Ovarian Cancer?

    DEFF Research Database (Denmark)

    Rasmussen, Christina B; Jensen, Allan; Albieri, Vanna;

    2016-01-01

    BACKGROUND: Pelvic inflammatory disease (PID) has been proposed as a risk factor for ovarian cancer. However, the existing literature on the association between PID and ovarian cancer risk is inconclusive, and only few cohort studies have been conducted. METHODS: Using nationwide Danish registries...

  4. 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....

  5. Biomarkers for predicting complete debulking in ovarian cancer

    DEFF Research Database (Denmark)

    Fagö-Olsen, Carsten Lindberg; Ottesen, Bent; Christensen, Ib Jarle;

    2014-01-01

    Aim: We aimed to construct and validate a model based on biomarkers to predict complete primary debulking surgery for ovarian cancer patients.......Aim: We aimed to construct and validate a model based on biomarkers to predict complete primary debulking surgery for ovarian cancer patients....

  6. 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....

  7. 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...

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

    Science.gov (United States)

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

  9. Ovarian, Fallopian Tube, and Primary Peritoneal Cancer Prevention

    Science.gov (United States)

    ... and primary peritoneal cancer: Oral contraceptives Taking oral contraceptives (“the pill”) lowers the risk of ovarian cancer. The longer oral contraceptives are used, the lower the risk may be. ...

  10. 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.

  11. 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.

  12. Characterization and proteomic analysis of ovarian cancer-derived exosomes.

    Science.gov (United States)

    Liang, Bing; Peng, Peng; Chen, She; Li, Lin; Zhang, Meijun; Cao, Dongyan; Yang, Jiaxin; Li, Haixia; Gui, Ting; Li, Xialu; Shen, Keng

    2013-03-27

    Ovarian cancer is the most lethal type of cancer among all frequent gynecologic malignancies, because most patients present with advanced disease at diagnosis. Exosomes are important intercellular communication vehicles, released by various cell types. Here we presented firstly the protein profile of highly purified exosomes derived from two ovarian cancer cell lines, OVCAR-3 and IGROV1. The exosomes derived from ovarian cancer cell lines were round and mostly 30-100 nm in diameter when viewed under an electron microscope. The exosomal marker proteins TSG101 and Alix were detected in exosome preparations. The range of density was between 1.09 g/ml and 1.15 g/ml. A total of 2230 proteins were identified from two ovarian cell-derived exosomes. Among them, 1017 proteins were identified in both exosomes including all of the major exosomal protein markers. There were 380 proteins that are not reported in the ExoCarta database. In addition to common proteins from exosomes of various origins, our results showed that ovarian cancer-derived exosomes also carried tissue specific proteins associated with tumorigenesis and metastasis, especially in ovarian carcinoma. Based on the known roles of exosomes in cellular communication, these data indicate that exosomes released by ovarian cancer cells may play important roles in ovarian cancer progression and provide a potential source of blood-based protein biomarkers.

  13. Obesity Exposure Across the Lifespan on Ovarian Cancer Pathogenesis

    Science.gov (United States)

    2015-08-01

    trial of metformin/paclitaxel/carboplatin in ovarian cancer patients. NOTE: This grant is to be reviewed on October 5th, 2015. REFERENCES 1...Obesity and the risk of epithelial ovarian cancer : a systematic review and meta-analysis. Eur J Cancer . 2007;43(4):690-709. PubMed PMID: 17223544. 4...cal months, 3% effort). Dr. Damania is a Professor in the Department of Microbiology and Immunology and a member of the Lineberger Comprehensive Cancer

  14. Screening for genes associated with ovarian cancer prognosis

    Institute of Scientific and Technical Information of China (English)

    CHANG Xiao-hong; ZHANG Li; YANG Rong; FENG Jie; CHENG Ye-xia; CHENG Hong-yan; YE Xue; FU Tian-yun; CUI Heng

    2009-01-01

    Background Human epithelial ovarian cancer cell line SKOV3.ipl is more invasive and metastatic compared with its parental line SKOV3. A total of 17 000 human genome complementary DNA microarrays were used to compare the gene expression patterns of the two cell lines. Based on this, the gene expression profiles of 22 patients with ovarian cancer were analyzed by cDNA microarray, and screened the 2-fold differentially expressed genes compared with the normal ones. We screened genes relevant to clinical prognosis of serous ovarian cancer by determining the expression profiles of ovarian cancer genes to investigate cell receptor and immunity-associated genes, and as groundwork, identify ovarian cancer-associated antigens at the gene level.Methods Total RNA was extracted from 22 patients with ovarian cancer and DNA microarrays were prepared. After scanning, hybridization signals were collected and the genes that were differentially expressed twice as compared with the normal ones were screened.Results We screened 236 genes relevant to the prognosis of ovarian cancer from the 17 000 human genome cDNA microarrays. According to gene classification, 48 of the 236 genes were cell receptor or immunity-associatad genes,including 2 genes related to the International Federation of Gynecology and Obstetrics (FIGO) stage, 4 genes to histological grade, 18 genes to lymph node metastasis, 11 genes to residual disease, and 13 genes to the reactivity to chemotherapy. Several functionally important genes including fibronectin 1, pericentriolar material 1, beta-2-microglobulin,PPAR binding protein were identified through review of the literature.Conclusions The cDNA microarray of ovarian cancer genes developed in this study was effective and high throughput in screening the ovarian cancer-associated genes differentially expressed. Through the studies of the cell receptor and immunity-associated genes we expect to identify the molecular biology index of ovarian cancer-associated antigens.

  15. 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 ...

  16. History of hypertension, heart disease, and diabetes and ovarian cancer patient survival: evidence from the ovarian cancer association consortium

    NARCIS (Netherlands)

    Minlikeeva, A.N.; Freudenheim, J.L.; Cannioto, R.A.; Szender, J.B.; Eng, K.H.; Modugno, F.; Ness, R.B.; LaMonte, M.J.; Friel, G.; Segal, B.H.; Odunsi, K.; Mayor, P.; Zsiros, E.; Schmalfeldt, B.; Klapdor, R.; Drk, T.; Hillemanns, P.; Kelemen, L.E.; Kbel, M.; Steed, H.; Fazio, A. de; Jordan, S.J.; Nagle, C.M.; Risch, H.A.; Rossing, M.A.; Doherty, J.A.; Goodman, M.T.; Edwards, R.; Matsuo, K.; Mizuno, M.; Karlan, B.Y.; Kjaer, S.K.; Hogdall, E.; Jensen, A.; Schildkraut, J.M.; Terry, K.L.; Cramer, D.W; Bandera, E.V.; Paddock, L.E.; Kiemeney, L.A.L.M.; Massuger, L.F.A.G.; Kupryjanczyk, J.; Berchuck, A.; Chang-Claude, J.; Diergaarde, B.; Webb, P.M.; Moysich, K.B.

    2017-01-01

    PURPOSE: Survival following ovarian cancer diagnosis is generally low; understanding factors related to prognosis could be important to optimize treatment. The role of previously diagnosed comorbidities and use of medications for those conditions in relation to prognosis for ovarian cancer patients

  17. VSGP/F-spondin: a new ovarian cancer marker.

    Science.gov (United States)

    Pyle-Chenault, Ruth A; Stolk, John A; Molesh, David A; Boyle-Harlan, Dianne; McNeill, Patricia D; Repasky, Elizabeth A; Jiang, Zhong; Fanger, Gary R; Xu, Jiangchun

    2005-01-01

    The discovery of genes that are overexpressed in ovarian cancers provides valuable insight into ovarian cancer biology and will lead to the development of more effective treatment strategies for combating this disease. To identify genes exhibiting ovarian- and ovarian cancer-specific expression, we generated four subtracted cDNA libraries from primary and metastatic ovarian adenocarcinoma tissues. 3,400 cDNA clones from these libraries were analyzed by microarray for tissue distribution and tumor specificity using 32 pairs of fluorophore-labeled cDNA samples from a variety of normal tissues and ovarian tumor tissues. cDNA clones showing elevated expression in ovarian tumors were identified by DNA sequencing with comparison to public databases, and the most promising candidates were further analyzed by quantitative real-time polymerase chain reaction and Northern blot. This systematic approach led to the identification of a number of genes including vascular smooth muscle growth-promoting factor (VSGP/F-spondin), a secreted protein previously identified and cloned from bovine and human ovary. VSGP/F-spondin protein was observed in ovarian carcinomas but not in normal ovarian epithelium by immunohistochemistry with a VSGP/F-spondin antibody. The expression profile of VSGP/F-spondin identifies this molecule as a potential diagnostic marker or target for developing therapeutic strategies to treat ovarian carcinoma.

  18. Surgery for advanced epithelial ovarian cancer.

    Science.gov (United States)

    Hacker, Neville F; Rao, Archana

    2016-10-20

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

  19. Cells of Origin of Epithelial Ovarian Cancers

    Science.gov (United States)

    2015-09-01

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

  20. Differential Cytotoxic Potential of Silver Nanoparticles in Human Ovarian Cancer Cells and Ovarian Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Yun-Jung Choi

    2016-12-01

    Full Text Available The cancer stem cell (CSC hypothesis postulates that cancer cells are composed of hierarchically-organized subpopulations of cells with distinct phenotypes and tumorigenic capacities. As a result, CSCs have been suggested as a source of disease recurrence. Recently, silver nanoparticles (AgNPs have been used as antimicrobial, disinfectant, and antitumor agents. However, there is no study reporting the effects of AgNPs on ovarian cancer stem cells (OvCSCs. In this study, we investigated the cytotoxic effects of AgNPs and their mechanism of causing cell death in A2780 (human ovarian cancer cells and OvCSCs derived from A2780. In order to examine these effects, OvCSCs were isolated and characterized using positive CSC markers including aldehyde dehydrogenase (ALDH and CD133 by fluorescence-activated cell sorting (FACS. The anticancer properties of the AgNPs were evaluated by assessing cell viability, leakage of lactate dehydrogenase (LDH, reactive oxygen species (ROS, and mitochondrial membrane potential (mt-MP. The inhibitory effect of AgNPs on the growth of ovarian cancer cells and OvCSCs was evaluated using a clonogenic assay. Following 1–2 weeks of incubation with the AgNPs, the numbers of A2780 (bulk cells and ALDH+/CD133+ colonies were significantly reduced. The expression of apoptotic and anti-apoptotic genes was measured by real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR. Our observations showed that treatment with AgNPs resulted in severe cytotoxicity in both ovarian cancer cells and OvCSCs. In particular, AgNPs showed significant cytotoxic potential in ALDH+/CD133+ subpopulations of cells compared with other subpopulation of cells and also human ovarian cancer cells (bulk cells. These findings suggest that AgNPs can be utilized in the development of novel nanotherapeutic molecules for the treatment of ovarian cancers by specific targeting of the ALDH+/CD133+ subpopulation of cells.

  1. Trastuzumab Sensitizes Ovarian Cancer Cells to EGFR-targeted Therapeutics

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    Wilken Jason A

    2010-03-01

    Full Text Available Abstract Background Early studies have demonstrated comparable levels of HER2/ErbB2 expression in both breast and ovarian cancer. Trastuzumab (Herceptin, a therapeutic monoclonal antibody directed against HER2, is FDA-approved for the treatment of both early and late stage breast cancer. However, clinical studies of trastuzumab in epithelial ovarian cancer (EOC patients have not met the same level of success. Surprisingly, however, no reports have examined either the basis for primary trastuzumab resistance in ovarian cancer or potential ways of salvaging trastuzumab as a potential ovarian cancer therapeutic. Methods An in vitro model of primary trastuzumab-resistant ovarian cancer was created by long-term culture of HER2-positive ovarian carcinoma-derived cell lines with trastuzumab. Trastuzumab treated vs. untreated parental cells were compared for HER receptor expression, trastuzumab sensitivity, and sensitivity to other HER-targeted therapeutics. Results In contrast to widely held assumptions, here we show that ovarian cancer cells that are not growth inhibited by trastuzumab are still responsive to trastuzumab. Specifically, we show that responsiveness to alternative HER-targeted inhibitors, such as gefitinib and cetuximab, is dramatically potentiated by long-term trastuzumab treatment of ovarian cancer cells. HER2-positive ovarian carcinoma-derived cells are, therefore, not "unresponsive" to trastuzumab as previously assumed, even when they not growth inhibited by this drug. Conclusions Given the recent success of EGFR-targeted therapeutics for the treatment of other solid tumors, and the well-established safety profile of trastuzumab, results presented here provide a rationale for re-evaluation of trastuzumab as an experimental ovarian cancer therapeutic, either in concert with, or perhaps as a "primer" for EGFR-targeted therapeutics.

  2. 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.

  3. Pelvic Inflammatory Disease and the Risk of Ovarian Cancer and Borderline Ovarian Tumors: A Pooled Analysis of 13 Case-Control Studies

    NARCIS (Netherlands)

    Rasmussen, C.B.; Kjaer, S.K.; Albieri, V.; Bandera, E.V.; Doherty, J.A.; Hogdall, E.; Webb, P.M.; Jordan, S.J.; Rossing, M.A.; Wicklund, K.G.; Goodman, M.T.; Modugno, F.; Moysich, K.B.; Ness, R.B.; Edwards, R.P.; Schildkraut, J.M.; Berchuck, A.; Olson, S.H.; Kiemeney, L.A.L.M.; Massuger, L.F.A.G.; Narod, S.A.; Phelan, C.M.; Anton-Culver, H.; Ziogas, A.; Wu, A.H.; Pearce, C.L.; Risch, H.A.; Jensen, A.

    2017-01-01

    Inflammation has been implicated in ovarian carcinogenesis. However, studies investigating the association between pelvic inflammatory disease (PID) and ovarian cancer risk are few and inconsistent. We investigated the association between PID and the risk of epithelial ovarian cancer according to

  4. Ovarian Cancer Treatment | Cancer Trends Progress Report

    Science.gov (United States)

    The Cancer Trends Progress Report, first issued in 2001, summarizes our nation's advances against cancer in relation to Healthy People targets set forth by the Department of Health and Human Services.

  5. 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

  6. 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

  7. Mesothelial cells promote early ovarian cancer metastasis through fibronectin secretion.

    Science.gov (United States)

    Kenny, Hilary A; Chiang, Chun-Yi; White, Erin A; Schryver, Elizabeth M; Habis, Mohammed; Romero, Iris L; Ladanyi, Andras; Penicka, Carla V; George, Joshy; Matlin, Karl; Montag, Anthony; Wroblewski, Kristen; Yamada, S Diane; Mazar, Andrew P; Bowtell, David; Lengyel, Ernst

    2014-10-01

    Ovarian cancer (OvCa) metastasizes to organs in the abdominal cavity, such as the omentum, which are covered by a single layer of mesothelial cells. Mesothelial cells are generally thought to be "bystanders" to the metastatic process and simply displaced by OvCa cells to access the submesothelial extracellular matrix. Here, using organotypic 3D cultures, we found that primary human mesothelial cells secrete fibronectin in the presence of OvCa cells. Moreover, we evaluated the tumor stroma of 108 human omental metastases and determined that fibronectin was consistently overexpressed in these patients. Blocking fibronectin production in primary mesothelial cells in vitro or in murine models, either genetically (fibronectin 1 floxed mouse model) or via siRNA, decreased adhesion, invasion, proliferation, and metastasis of OvCa cells. Using a coculture model, we determined that OvCa cells secrete TGF-β1, which in turn activates a TGF-β receptor/RAC1/SMAD-dependent signaling pathway in the mesothelial cells that promotes a mesenchymal phenotype and transcriptional upregulation of fibronectin. Additionally, blocking α5 or β1 integrin function with antibodies reduced metastasis in an orthotopic preclinical model of OvCa metastasis. These findings indicate that cancer-associated mesothelial cells promote colonization during the initial steps of OvCa metastasis and suggest that mesothelial cells actively contribute to metastasis.

  8. Prognostic values of aldehyde dehydrogenase 1 isoenzymes in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Ma YM

    2016-04-01

    Full Text Available Yu-mei Ma,1 Shan Zhao2 1Department of Pathology, 2Department of Cancer Second Division, The Second Hospital of Hebei Medical University, Shijiazhuang City, People’s Republic of China Abstract: Aldehyde dehydrogenase 1 (ALDH1 activity has been used as a functional stem cell marker to isolate cancer stem cells in different cancer types, including ovarian cancer. However, which ALDH1’s isoenzymes are contributing to ALDH1 activity in ovarian cancer remains elusive. In addition, the prognostic value of an individual ALDH1 isoenzyme in ovarian cancer is not clear. Thus, we accessed the prognostic value of ALDH1 isoenzymes in ovarian cancer patients through the “Kaplan–Meier plotter” online database, which can be used to determine the effect of the genes on ovarian cancer prognosis. We found that high mRNA expression of five ALDH1 isoenzymes, such as ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, and ALDH1L1, was not correlated with overall survival (OS for all 1,306 ovarian cancer patients. In addition, all five of the ALDH1 isoenzymes’ high mRNA expression was found to be uncorrelated with OS in serous cancer or endometrioid cancer patients. However, ALDH1A3’s high mRNA expression is associated with worse OS in grade II ovarian cancer patients, hazard ratio (HR 1.53 (1.14–2.07, P=0.005. ALDH1A2’s high mRNA expression is significantly associated with worse OS in TP53 wild-type ovarian cancer patients, HR 2.86 (1.56–5.08, P=0.00036. In addition, ALDH1A3’s high mRNA expression is significantly associated with better OS in TP53 wild-type ovarian cancer patients, HR 0.56 (0.32–1.00, P=0.04. Our results indicate that although ALDH1 isoenzyme mRNA might not be a prognostic marker for overall ovarian cancer patients, some isoenzymes, such as ALDH1A2 and ALDH1A3, might be a good prognostic marker for some types of ovarian cancer patients. Keywords: ALDH1, cancer stem cell, prognosis, KM plotter, hazard ratio

  9. Epidemiology of ovarian cancer: a review.

    Science.gov (United States)

    Reid, Brett M; Permuth, Jennifer B; Sellers, Thomas A

    2017-02-01

    Ovarian cancer (OC) is the seventh most commonly diagnosed cancer among women in the world and the tenth most common in China. Epithelial OC is the most predominant pathologic subtype, with five major histotypes that differ in origination, pathogenesis, molecular alterations, risk factors, and prognosis. Genetic susceptibility is manifested by rare inherited mutations with high to moderate penetrance. Genome-wide association studies have additionally identified 29 common susceptibility alleles for OC, including 14 subtype-specific alleles. Several reproductive and hormonal factors may lower risk, including parity, oral contraceptive use, and lactation, while others such as older age at menopause and hormone replacement therapy confer increased risks. These associations differ by histotype, especially for mucinous OC, likely reflecting differences in etiology. Endometrioid and clear cell OC share a similar, unique pattern of associations with increased risks among women with endometriosis and decreased risks associated with tubal ligation. OC risks associated with other gynecological conditions and procedures, such as hysterectomy, pelvic inflammatory disease, and polycystic ovarian syndrome, are less clear. Other possible risk factors include environmental and lifestyle factors such as asbestos and talc powder exposures, and cigarette smoking. The epidemiology provides clues on etiology, primary prevention, early detection, and possibly even therapeutic strategies.

  10. Laparoscopic cytoreduction for primary advanced ovarian cancer.

    Science.gov (United States)

    Fanning, James; Hojat, Rod; Johnson, Jil; Fenton, Bradford

    2010-01-01

    We evaluated the feasibility of laparoscopic cytoreduction for primary advanced ovarian cancer. All patients with presumed stage 3/4 primary ovarian cancer underwent attempted laparoscopic cytoreduction. All patients had CT evidence of omental metastasis and ascites. A 5-port (5-mm) transperitoneal approach was used. A bilateral salpingo-oophorectomy, supracervical hysterectomy, and omentectomy were performed with PlasmaKinetic (PK) cutting forceps. A laparoscopic 5-mm Argon-Beam Coagulator was used to coagulate tumor in the pelvis, abdominal peritoneum, intestinal mesentery, and diaphragm. Nine of 11 cases (82%) were successfully debulked laparoscopically without conversion to laparotomy. Median operative time was 2.5 hours, and median blood loss was 275 mL. All tumors were debulked to <2 cm and 45% had no residual disease. Stages were 1-3B, 7-3C, and 1-4. Median length of stay was one day. Median VAS pain score was 4 (discomforting). Two of 11 patients (18%) had postoperative complications. Laparoscopic cytoreduction was successful and resulted in minimal morbidity. Because of our small sample size, additional studies are needed.

  11. Distinct metabolic responses of an ovarian cancer stem cell line.

    Science.gov (United States)

    Vermeersch, Kathleen A; Wang, Lijuan; McDonald, John F; Styczynski, Mark P

    2014-12-18

    Cancer metabolism is emerging as an important focus area in cancer research. However, the in vitro cell culture conditions under which much cellular metabolism research is performed differ drastically from in vivo tumor conditions, which are characterized by variations in the levels of oxygen, nutrients like glucose, and other molecules like chemotherapeutics. Moreover, it is important to know how the diverse cell types in a tumor, including cancer stem cells that are believed to be a major cause of cancer recurrence, respond to these variations. Here, in vitro environmental perturbations designed to mimic different aspects of the in vivo environment were used to characterize how an ovarian cancer cell line and its derived, isogenic cancer stem cells metabolically respond to environmental cues. Mass spectrometry was used to profile metabolite levels in response to in vitro environmental perturbations. Docetaxel, the chemotherapeutic used for this experiment, caused significant metabolic changes in amino acid and carbohydrate metabolism in ovarian cancer cells, but had virtually no metabolic effect on isogenic ovarian cancer stem cells. Glucose deprivation, hypoxia, and the combination thereof altered ovarian cancer cell and cancer stem cell metabolism to varying extents for the two cell types. Hypoxia had a much larger effect on ovarian cancer cell metabolism, while glucose deprivation had a greater effect on ovarian cancer stem cell metabolism. Core metabolites and pathways affected by these perturbations were identified, along with pathways that were unique to cell types or perturbations. The metabolic responses of an ovarian cancer cell line and its derived isogenic cancer stem cells differ greatly under most conditions, suggesting that these two cell types may behave quite differently in an in vivo tumor microenvironment. While cancer metabolism and cancer stem cells are each promising potential therapeutic targets, such varied behaviors in vivo would need to

  12. Expression of tumor antigens on primary ovarian cancer cells compared to established ovarian cancer cell lines

    Science.gov (United States)

    Kloudová, Kamila; Hromádková, Hana; Partlová, Simona; Brtnický, Tomáš; Rob, Lukáš; Bartůňková, Jiřina; Hensler, Michal; Halaška, Michael J.; Špíšek, Radek; Fialová, Anna

    2016-01-01

    In order to select a suitable combination of cancer cell lines as an appropriate source of antigens for dendritic cell-based immunotherapy of ovarian cancer, we analyzed the expression level of 21 tumor associated antigens (BIRC5, CA125, CEA, DDX43, EPCAM, FOLR1, Her-2/neu, MAGE-A1, MAGE-A2, MAGE-A3, MAGE-A4, MAGE-A6, MAGE-A10, MAGE-A12, MUC-1, NY-ESO-1, PRAME, p53, TPBG, TRT, WT1) in 4 established ovarian cancer cell lines and in primary tumor cells isolated from the high-grade serous epithelial ovarian cancer tissue. More than 90% of tumor samples expressed very high levels of CA125, FOLR1, EPCAM and MUC-1 and elevated levels of Her-2/neu, similarly to OVCAR-3 cell line. The combination of OV-90 and OVCAR-3 cell lines showed the highest overlap with patients' samples in the TAA expression profile. PMID:27323861

  13. 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.......19, 2.01). CONCLUSIONS: Genetically lowered 25-hydroxyvitamin D concentrations were associated with higher ovarian cancer susceptibility in Europeans. These findings suggest that increasing plasma vitamin D levels may reduce risk of ovarian cancer....... of observational studies is inadequate control of confounding. To overcome this problem, we used Mendelian randomization (MR) to evaluate the association between single nucleotide polymorphisms (SNPs) associated with circulating 25-hydroxyvitamin D [25(OH)D] concentration and risk of ovarian cancer. METHODS: We...

  14. 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.

  15. Complications from Surgeries Related to Ovarian Cancer Screening.

    Science.gov (United States)

    Baldwin, Lauren A; Pavlik, Edward J; Ueland, Emma; Brown, Hannah E; Ladd, Kelsey M; Huang, Bin; DeSimone, Christopher P; van Nagell, John R; Ueland, Frederick R; Miller, Rachel W

    2017-03-08

    The aim of this study was to evaluate complications of surgical intervention for participants in the Kentucky Ovarian Cancer Screening Program and compare results to those of the Prostate, Lung, Colorectal and Ovarian Cancer Screening trial. A retrospective database review included 657 patients who underwent surgery for a positive screen in the Kentucky Ovarian Cancer Screening Program from 1988-2014. Data were abstracted from operative reports, discharge summaries, and office notes for 406 patients. Another 142 patients with incomplete records were interviewed by phone. Complete information was available for 548 patients. Complications were graded using the Clavien-Dindo (C-D) Classification of Surgical Complications and considered minor if assigned Grade I (any deviation from normal course, minor medications) or Grade II (other pharmacological treatment, blood transfusion). C-D Grade III complications (those requiring surgical, endoscopic, or radiologic intervention) and C-D Grade IV complications (those which are life threatening) were considered "major". Statistical analysis was performed using SAS 9.4 software. Complications were documented in 54/548 (10%) subjects. For women with malignancy, 17/90 (19%) had complications compared to 37/458 (8%) with benign pathology (p Cancer Screening trial, 212 women had surgery for ovarian malignancy, and 95 had at least one complication (45%). Of the 1080 women with non-cancer surgery, 163 had at least one complication (15%). Compared to the Prostate, Lung, Colorectal and Ovarian Cancer Screening trial, the Kentucky Ovarian Cancer Screening Program had significantly fewer complications from both cancer and non-cancer surgery (p Cancer Screening Program were infrequent and significantly fewer than reported in the Prostate, Lung, Colorectal and Ovarian Cancer Screening trial. Complications were mostly minor (93%) and were more common in cancer versus non-cancer surgery.

  16. Occupational exposure and ovarian cancer risk.

    Science.gov (United States)

    Le, Nhu D; Leung, Andy; Brooks-Wilson, Angela; Gallagher, Richard P; Swenerton, Kenneth D; Demers, Paul A; Cook, Linda S

    2014-07-01

    Relatively little work has been done concerning occupational risk factors in ovarian cancer. Although studies conducted in occupational settings have reported positive associations, their usefulness is generally limited by the lack of information on important confounders. In a population-based case-control study, we assessed risk for developing epithelial ovarian cancer (EOC) associated with occupational exposure while accounting for important confounders. Participants were identified through provincial population-based registries. Lifetime occupational history and information on potential confounding factors were obtained through a self-administered questionnaire. Unconditional logistic regression and the likelihood ratio test were used to assess EOC risk with each occupation (or industry), relative to all other occupations (or industries), adjusting for potential confounders including body mass index, oral contraceptive use, menopausal hormone therapy, parity, age at first childbirth, age at menarche, age at menopause, family history of breast and ovarian cancer in mother and sister(s), tubal ligation, partial oophorectomy, and hysterectomy. Occupations and industries were coded according to the Canadian Standard Occupational Classification (SOC) and Standard Industrial Classification (SIC). Significant excess risk was observed for several groups of teaching occupations, including SOC 27, teaching and related (adjusted OR 1.77, 95% CI 1.15-2.81) and SOC 279, other teaching and related (adjusted OR 3.11, 95% CI 1.35-8.49). Significant excess was also seen for a four-digit occupational group SOC 4131, bookkeepers and accounting clerks (adjusted OR 2.80, 95% CI 1.30-6.80). Industrial sub-groups showing significant excess risk included SIC 65, other retail stores (adjusted OR 2.19, 95 % CI 1.16-4.38); SIC 85, educational service (adjusted OR 1.45, 95% CI 1.00-2.13); and SIC 863, non-institutional health services (adjusted OR 2.54, 95% CI 1.13-6.52). Our study found

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

    OpenAIRE

    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

    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...

  18. 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

  19. 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

  20. 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.

  1. Lymphadenectomy in surgical stage I epithelial ovarian cancer

    DEFF Research Database (Denmark)

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

    2014-01-01

    OBJECTIVE: To identify the extent of lymphadenectomy performed in women presenting with epithelial ovarian cancer macroscopically confined to the ovary. Furthermore, the effect of lymphadenectomy on overall survival is evaluated. DESIGN: A prospective nationwide case-only study. SETTING: Denmark ...

  2. 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.

  3. 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...... this, we used two endometriosis datasets genotyped on common arrays with full-genome coverage (3194 cases and 7060 controls) and a large ovarian cancer dataset genotyped on the customized Illumina Infinium iSelect (iCOGS) arrays (10 065 cases and 21 663 controls). Previous work has suggested...... that a large number of genetic variants contribute to endometriosis and ovarian cancer (all histotypes combined) susceptibility. Here, using the iCOGS data, we confirmed polygenic architecture for most histotypes of ovarian cancer. This led us to evaluate if the polygenic effects are shared across diseases. We...

  4. Defining Therapy for Recurrent Platinum-sensitive Ovarian Cancer

    Science.gov (United States)

    In this phase III clinical trial, women with platinum-sensitive, recurrent ovarian epithelial, fallopian tube, or primary peritoneal cancer will be randomly assigned to undergo secondary cytoreductive surgery, if they are candidates for such surgery, and

  5. General Information About Ovarian, Fallopian Tube, and Primary Peritoneal Cancer

    Science.gov (United States)

    ... precancerous condition or to keep cancer from starting. General Information About Ovarian, Fallopian Tube, and Primary Peritoneal ... the peritoneum and spreads to the ovary. Enlarge Anatomy of the female reproductive system. The organs in ...

  6. 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 ...

  7. Discovery – BRCA Connection to Breast and Ovarian Cancer

    Science.gov (United States)

    NCI-funded research helped identify inherited BRCA1 and BRCA2 genetic mutations and their connection to breast and ovarian cancer. From this research, a screening test was also developed to help patients make informed decisions about their health.

  8. Surgery and Chemotherapy With or Without Chemotherapy After Surgery in Treating Patients With Ovarian, Fallopian Tube, Uterine, or Peritoneal Cancer

    Science.gov (United States)

    2016-10-18

    Recurrent Uterine Corpus Cancer; Recurrent Fallopian Tube Cancer; Recurrent Ovarian Cancer; Recurrent Primary Peritoneal Cancer; Stage IIIA Uterine Corpus Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cavity Cancer; Stage IIIB Uterine Corpus Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cavity Cancer; Stage IIIC Uterine Corpus Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cavity Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cavity Cancer; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer

  9. Psychosocial Stress and Ovarian Cancer Risk: Metabolomics and Perceived Stress

    Science.gov (United States)

    2015-10-01

    metabolomic profiling of women with and without post- traumatic stress disorder (PTSD) to derive a signature of chronic stress and then apply that metabolomic...noted that phobic anxiety and social isolation were suggestively associated with increased risk of ovarian cancer (hazard ratios of 1.14 and 1.24...TERMS ovarian cancer, psychosocial stress, depression, anxiety , social support, metabolomics 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF

  10. Perineal use of talc and risk of ovarian cancer.

    Science.gov (United States)

    Langseth, H; Hankinson, S E; Siemiatycki, J; Weiderpass, E

    2008-04-01

    Ovarian cancer is one of the most common gynaecological neoplasms, especially in industrialised countries. The aetiology of the disease is not well understood, except that inherited mutations in the breast cancer genes BRCA-1 and BRCA-2 account for up to 10% of all cases, and child-bearing, oral contraceptive use and breast-feeding reduce the risk. Some environmental exposures, notably talc and asbestos, have been suspected as ovarian carcinogens.

  11. 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.

  12. Ovarian cancer: a molecularly insidious disease.

    Science.gov (United States)

    Mezzanzanica, Delia

    2015-01-01

    In this issue of the Chinese Journal of Cancer, European, American, and Chinese experts review the current management and future perspectives of epithelial ovarian cancer (EOC), the leading cause of gynecological cancer deaths. Although major advances have been made in understanding the cellular and molecular biology of this highly heterogeneous malignancy, the survival rate of women with EOC has changed little since the introduction of platinum-based treatment as a front-line therapy. The papers describe the progress in deciphering the molecular complexity of this disease and the newly available molecular-driven therapies, which have been applied by shifting trial designs toward restricting eligibility to specific subgroups of patients rather than testing agents in unselected populations. These new trial designs provide potential opportunities for improved efficacy in targeted populations. Given the molecular complexity of this disease, patient survival may be increased by searching for new molecular prognostic/predictive signatures as well as by translating the recent insight of microRNA involvement in EOC progression into new, targeted therapies. Particular attention has been given to the issue of fertility sparing for women affected by curable diseases.

  13. Enhancing chemotherapy response with Bmi-1 silencing in ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Enfeng Wang

    Full Text Available Undoubtedly ovarian cancer is a vexing, incurable disease for patients with recurrent cancer and therapeutic options are limited. Although the polycomb group gene, Bmi-1 that regulates the self-renewal of normal stem and progenitor cells has been implicated in the pathogenesis of many human malignancies, yet a role for Bmi-1 in influencing chemotherapy response has not been addressed before. Here we demonstrate that silencing Bmi-1 reduces intracellular GSH levels and thereby sensitizes chemoresistant ovarian cancer cells to chemotherapeutics such as cisplatin. By exacerbating ROS production in response to cisplatin, Bmi-1 silencing activates the DNA damage response pathway, caspases and cleaves PARP resulting in the induction apoptosis in ovarian cancer cells. In an in vivo orthotopic mouse model of chemoresistant ovarian cancer, knockdown of Bmi-1 by nanoliposomal delivery significantly inhibits tumor growth. While cisplatin monotherapy was inactive, combination of Bmi-1 silencing along with cisplatin almost completely abrogated ovarian tumor growth. Collectively these findings establish Bmi-1 as an important new target for therapy in chemoresistant ovarian cancer.

  14. 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.

  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. Predictors of pretreatment CA125 at ovarian cancer diagnosis

    DEFF Research Database (Denmark)

    Babic, Ana; Cramer, Daniel W; Kelemen, Linda E

    2017-01-01

    PURPOSE: Cancer antigen 125 (CA125) is a glycoprotein expressed by epithelial cells of several normal tissue types and overexpressed by several epithelial cancers. Serum CA125 levels are mostly used as an aid in the diagnosis of ovarian cancer patients, to monitor response to treatment and detect...

  17. 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.

  18. Investigate the Role of Obesity in Ovarian Cancer Initiation and Progression

    Science.gov (United States)

    2016-05-01

    AWARD NUMBER: W81XWH-15-1-0095 TITLE: Investigate the Role of Obesity in Ovarian Cancer Initiation and Progression PRINCIPAL INVESTIGATOR...TITLE AND SUBTITLE Investigate the Role of Obesity in Ovarian Cancer Initiation and Progression 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-15-1...pathways in ovarian stem cells and in transformed ovarian cells affected by obesity that lead to ovarian cancer initiation and progression. 15. SUBJECT

  19. 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.

  20. 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. |

  1. SiRNA and epigenetic aberrations in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Hamed Mirzaei

    2016-01-01

    Full Text Available Ovarian cancer has the most noteworthy lethal rate around gynecologic malignancies, and it is also considered as the fourth most frequent cancer in the woman in world. Two most critical barriers to treatment of ovarian malignancy are absence of early diagnostic markers and advancement of drug resistance after therapy, especially in advanced stages. Various epigenetic changes have been recognized in ovarian cancer. Recent progresses in our understanding of molecular pathogenesis of ovarian malignancy have dramatically provided potential new targets for molecularly targeted therapies. In very recent years, small interfering RNA (siRNA-mediated gene silencing has been emerging as a novel treatment modality in preclinical studies in the light of its strong gene-specific silencing. Gene suppression mediated by RNA interference (RNAi significantly suppressed gene expression at the messenger RNA (mRNA and protein levels. SiRNAs have therapeutic potential for ovarian cancer through various mechanisms. In this review, we not only provide an overview of siRNA designing for epigenetic silencing of genes aberrantly expressed in ovarian cancer but also we will highlight that the epigenetically silenced genes offer new targets for therapeutic approaches based on re-expression of tumor suppressor genes via demethylating and deacetylating drugs.

  2. 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.

  3. 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,

  4. 77 FR 41791 - Proposed Collection; Comment Request; Prostate, Lung, Colorectal and Ovarian Cancer Screening...

    Science.gov (United States)

    2012-07-16

    ..., Colorectal and Ovarian Cancer Screening Trial (PLCO) (NCI) SUMMARY: In compliance with the requirement of... Ovarian Cancer Screening Trial (PLCO) (NCI). Type of Information Collection Request: Revision (OMB : 0925... designed to determine if cancer screening for prostate, lung, colorectal, and ovarian cancer can...

  5. Ovarian cancer: density equalizing mapping of the global research architecture.

    Science.gov (United States)

    Brüggmann, Dörthe; Pulch, Katharina; Klingelhöfer, Doris; Pearce, Celeste Leigh; Groneberg, David A

    2017-01-13

    Despite its impact on female health worldwide, no efforts have been made to depict the global architecture of ovarian cancer research and to understand the trends in the related literature. Hence, it was the objective of this study to assess the global scientific performance chronologically, geographically and in regards to economic benchmarks using bibliometric tools and density equalizing map projections. The NewQIS platform was employed to identify all ovarian cancer related articles published in the Web of Science since 1900. The items were analyzed regarding quantitative aspects (e.g. publication date, country of origin) and parameters describing the recognition of the work by the scientific community (e.g. citation rates). 23,378 articles on ovarian cancer were analyzed. The USA had the highest activity of ovarian cancer research with a total of n = 9312 ovarian cancer-specific publications, followed by the UK (n = 1900), China (n = 1813), Germany (n = 1717) and Japan (n = 1673). Ovarian cancer-specific country h-index also showed a leading position of the USA with an h-index (HI) of 207, followed by the UK (HI = 122), Canada (HI = 99), Italy (HI = 97), Germany (HI = 84), and Japan (HI = 81). In the socio-economic analysis, the USA were ranked first with an average of 175.6 ovarian cancer-related publications per GDP per capita in 1000 US-$, followed by Italy with an index level of 46.85, the UK with 45.48, and Japan with 43.3. Overall, the USA and Western European nations, China and Japan constituted the scientific power players publishing the majority of highly cited ovarian cancer-related articles and dominated international collaborative efforts. African, Asian and South American countries played almost no visible role in the scientific community. The quantity and scientific recognition of publications related to ovarian cancer are continuously increasing. The research endeavors in the field are concentrated in high-income countries

  6. CD133 antigen expression in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Prisco Maria

    2009-07-01

    Full Text Available Abstract Background Much attention has been recently focused on the role of cancer stem cells (CSCs in the initiation and progression of solid malignancies. Since CSCs are able to proliferate and self-renew extensively, thus sustaining tumor growth, the identification of CSCs through their antigenic profile might have relevant clinical implications. In this context, CD133 antigen has proved to be a marker of tumor cells with stemness features in several human malignancies. The aim of the study was to investigate the clinical role of the immunohistochemically assessed expression of CD133 in a large single Institution series of ovarian cancer patients. Methods The study included 160 cases admitted to the Gynecologic Oncology Unit, Catholic University of Campobasso and Rome. CD133 antigen was identified by the monoclonal mouse anti-CD133-1 antibody (clone CD133 Miltenyi biotec. Results In the overall series CD133 positive tumor cells were observed in 50/160 (31.2% cases. A diffuse cytoplasmic pattern was identified in 30/50 (60.0%, while an apical cytoplasmic pattern was found in 20/50 (40.0% of CD133 positive tumors. As of September 2008, the median follow up was 37 months (range: 2–112. During the follow up period, progression and death of disease were observed in 123 (76.9%, and 88 (55.0% cases, respectively. There was no difference in TTP between cases with negative (median TTP = 23 months versus positive CD133 expression (median TTP = 24 months (p value = 0.3. Similar results were obtained for OS. When considering the TTP and OS curves according to the pattern of CD133 expression, a trend to a worse prognosis for cases with diffuse cytoplasmic versus the apical cytoplasmic pattern was documented, although the statistical significance was not reached. Conclusion The immunohistochemical assessment of CD133 expression seems not to provide additional prognostic information in ovarian cancer patients. The role of the different pattern of CD133

  7. Cellular and molecular processes in ovarian cancer metastasis. A Review in the Theme: Cell and Molecular Processes in Cancer Metastasis.

    Science.gov (United States)

    Yeung, Tsz-Lun; Leung, Cecilia S; Yip, Kay-Pong; Au Yeung, Chi Lam; Wong, Stephen T C; Mok, Samuel C

    2015-10-01

    Ovarian cancer is the most lethal gynecological malignancy. It is usually diagnosed at a late stage, with a 5-yr survival rate of rethinking of the mode of ovarian cancer metastasis and the importance of the "seed-and-soil" hypothesis for ovarian cancer metastasis. In this review we discuss the possible mechanisms by which ovarian cancer cells metastasize from the primary tumor to the omentum, the cross-talk signaling events between ovarian cancer cells and various stromal cells that play crucial roles in ovarian cancer metastasis, and the possible clinical implications of these findings in the management of this deadly, highly metastatic disease.

  8. MicroRNA-873 mediates multidrug resistance in ovarian cancer cells by targeting ABCB1.

    Science.gov (United States)

    Wu, Di-di; Li, Xue-Song; Meng, Xiao-Na; Yan, Jing; Zong, Zhi-Hong

    2016-08-01

    Ovarian cancer is commonly treated with cisplatin and paclitaxel combination chemotherapy; however, ovarian cancer cells often develop resistance to these drugs. Increasingly, microRNAs (miRNAs) including miR-873 have been implicated in drug resistance in many cancers, but the role of miR-873 in ovarian cancer remains unknown. MTT cell viability assays revealed that the sensitivities of ovarian cancer lines to cisplatin and paclitaxel increased following transfection with miR-873 (P ovarian cancer in vivo (P ovarian cancer lines OVCAR3 and A2780 to cisplatin and paclitaxel, which can be reversed by miR-873 mimic transfection (P ovarian cancer cells to cisplatin and paclitaxel by targeting MDR1 expression. Our findings suggest that combination therapies with chemotherapy agents and miR-873 may suppress drug resistance in ovarian cancer.

  9. 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...

  10. Carboplatin and Gemcitabine Hydrochloride With or Without ATR Kinase Inhibitor VX-970 in Treating Patients With Recurrent and Metastatic Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

    Science.gov (United States)

    2017-01-31

    High Grade Ovarian Serous Adenocarcinoma; Ovarian Endometrioid Tumor; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer

  11. 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.

  12. Targeted therapy of ovarian cancer including immune check point inhibitor.

    Science.gov (United States)

    Kim, Jin Young; Cho, Chi Heum; Song, Hong Suk

    2017-08-22

    Epithelial ovarian cancer is the eighth most common cause of cancer-related deaths in women because most patients present with advanced stage disease at the time of diagnosis. Although cytoreductive surgery and platinum-based chemotherapy remain the gold standards of treatment, the recurrence rate of ovarian cancer remains high. Attempts to improve this standard two-drug chemotherapy by adding a third cytotoxic drug have failed to affect either progression-free survival or overall survival and have resulted in an increase in toxic side effects. Some anti-angiogenic agents, poly(ADP-ribose) polymerase, and immune checkpoint inhibitors have shown efficacy in early stages of development for the treatment of epithelial ovarian cancer. As demonstrated in recent clinical trials, the use of bevacizumab, cediranib, pazopanib, olaparib, and rucaparib, either alone or in combination with conventional cytotoxic agents, improves progression-free survival. Trials on immune checkpoint inhibitors such as nivolumab have revealed prolonged responses in a small set of ovarian cancer cases but require further exploration. In this review, we discuss the role of targeted therapies against ovarian cancer, including the use of immune checkpoint inhibitors.

  13. 3 CFR 8407 - Proclamation 8407 of August 31, 2009. National Ovarian Cancer Awareness Month, 2009

    Science.gov (United States)

    2010-01-01

    ... of the United States of America A Proclamation Ovarian cancer remains the leading cause of death from... the disease with grace and dignity. National Ovarian Cancer Awareness Month honors all those affected...

  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....

  15. Olaparib treatment for BRCA-mutant ovarian cancer with leptomeningeal disease

    OpenAIRE

    Bangham, Madeleine; Goldstein, Robert; Walton, Henry; Ledermann, Jonathan A.

    2016-01-01

    Highlights • Leptomeningeal disease occurs more commonly in BRCA-mutated ovarian cancer. • A clinically significant dose of olaprib is able to penetrate the leptomeninges. • Leptomeningeal metastases in a BRCA-mutated ovarian cancer responded to olaparib.

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  17. Association between genetic polymorphisms of inflammatory response genes and the risk of ovarian cancer

    Directory of Open Access Journals (Sweden)

    Zhi-Hui Lu

    2016-01-01

    Conclusion: NFKB1 and ICAM-1 polymorphisms could serve as useful ovarian cancer risk prediction biomarkers for the Chinese population, while the utility of PPARG and E-selectin polymorphisms as biomarkers requires further confirmation in independent ovarian cancer cohorts.

  18. Breast cancer following ovarian cancer in BRCA mutation carriers.

    Science.gov (United States)

    Gangi, Alexandra; Cass, Ilana; Paik, Daniel; Barmparas, Galinos; Karlan, Beth; Dang, Catherine; Li, Andrew; Walsh, Christine; Rimel, Bobbie J; Amersi, Farin F

    2014-12-01

    BRCA mutation carriers are at increased risk of developing breast cancer. However, the incidence of breast cancer after a diagnosis of epithelial ovarian cancer (EOC), one of the tubal/peritoneal cancers collectively referred to as pelvic serous carcinomas, is not well known. Optimal breast cancer surveillance and detection for these patients have also not been well characterized. To determine the incidence of breast cancer after a diagnosis of EOC and to evaluate the need for breast cancer surveillance for these patients. A retrospective database review of 364 patients who underwent BRCA mutation testing for EOC (stages I-IV) between 1998 and 2012 at an academic medical center with gynecologic and breast cancer centers. Incidence of breast cancer and methods of surveillance. Of 364 patients, 135 (37.1%) were found to carry a germline BRCA1 or BRCA2 mutation. The mean age of patients at diagnosis of EOC was 49.5 years (range, 28-89 years). Of the 135 patients, 12 (8.9%) developed breast cancer. The median time from diagnosis of EOC to diagnosis of breast cancer was 50.5 months. Annual mammography was performed for 80 patients (59.3%), with annual magnetic resonance imaging of the breasts performed for 60 patients (44.4%). Thirteen patients (9.6%) underwent a bilateral prophylactic mastectomy at a median of 23 months following EOC diagnosis. Breast cancer was most commonly diagnosed by mammography for 7 of the 12 patients (58.3%), 3 (25.0%) of whom had a palpable mass and 2 (16.7%) of whom had incidental breast cancer detected during a prophylactic mastectomy. Seven patients with breast cancer (58.3%) underwent a bilateral mastectomy. All patients had early-stage breast cancer (stages 0-II). Four patients (33.3%) received adjuvant chemotherapy. At a median follow-up of 6.3 years, 4 of the 12 patients (33.3%) died of recurrent EOC after a diagnosis of breast cancer. The overall 10-year survival rate for the entire cohort of 135 patients was 17.0%. The risk of

  19. 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.

  20. Past, present and future targets for immunotherapy in ovarian cancer.

    Science.gov (United States)

    Schwab, Carlton L; English, Diana P; Roque, Dana M; Pasternak, Monica; Santin, Alessandro D

    2014-01-01

    Ovarian cancer is the leading cause of death from gynecologic malignancy in the US. Treatments have improved with conventional cytotoxic chemotherapy and advanced surgical techniques but disease recurrence is common and fatal in nearly all cases. Current evidence suggests that the immune system and its ability to recognize and eliminate microscopic disease is paramount in preventing recurrence. Ovarian cancer immunotherapy is targeting tumors through active, passive and adoptive approaches. The goal of immunotherapy is to balance the activation of the immune system against cancer while preventing the potential for tremendous toxicity elicited by immune modulation. In this paper we will review the different immunotherapies available for ovarian cancer as well as current ongoing studies and potential future directions.

  1. 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

  2. Production of IL1-beta by ovarian cancer cells induces mesothelial cell beta1-integrin expression facilitating peritoneal dissemination

    Directory of Open Access Journals (Sweden)

    Watanabe Takafumi

    2012-02-01

    Full Text Available Abstract Background A crucial step in the metastatic spread of ovarian cancer (OC is the adhesion and implantation of tumor cells to the peritoneal mesothelium. In order to study this step in the cascade, we derived a pro-metastatic human ovarian carcinoma cell line (MFOC3 from the non-metastatic FOC3 line. Methods Molecular profiling of the isogeneic lines identified differentially expressed genes, and investigation for a role in dissemination for specific factors was achieved by development of a co-culture adhesion assay utilizing monolayers of human mesothelial cells. Results After murine intraperitoneal inoculation, the FOC3 cell line formed no metastases, but the MFOC3 subline formed metastases in > 80% of SCID mice. MFOC3 cells also adhered 2-3 times more avidly to mesothelial monolayers. This adhesion was inhibited by neutralizing antibodies to IL-1β and enhanced by recombinant IL-1β (p in vitro and significantly reduced metastases in vivo. Immunohistochemical analysis of a cohort of 96 ovarian cancer cases showed that negative IL-1β expression was significantly associated with an improved overall survival rate. Conclusions These results suggest that a IL-1β/β1-integrin axis plays a role in ovarian tumor cell adhesion to mesothelia, a crucial step in ovarian cancer dissemination.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  4. Study examines outcomes from surgery to prevent ovarian cancer

    Science.gov (United States)

    A new study looked at women at high risk of ovarian cancer who had no clinical signs of the disease and who underwent risk-reducing salpingo-oophorectomy (RRSO). The study results showed cancer in the removed tissues of 2.6 percent (25 of 966) of the par

  5. Factors affecting the association of oral contraceptives and ovarian cancer.

    Science.gov (United States)

    Cramer, D W; Hutchison, G B; Welch, W R; Scully, R E; Knapp, R C

    1982-10-21

    We investigated the relation between epithelial ovarian cancer and the use of oral contraceptives in a case-control study of 144 white women under the age of 60 who had ovarian cancer and 139 white women under 60 who were selected from the general population. We observed a decreased risk for ovarian cancer associated with the use of oral contraceptives in subjects 40 through 59 years of age at the time of the study. The relative risk, adjusted for parity, was 0.11, with 95 per cent confidence limits of 0.04 to 0.33. In contrast to the findings in older women, a decreased risk for ovarian cancer associated with oral-contraceptive use was not found in women under 40. In this group, the adjusted relative risk associated with any use of oral contraceptives was 1.98, with 95 per cent confidence limits of 0.74 to 5.27. The lowest risk for ovarian cancer associated with the use of oral contraceptives was observed in older parous subjects and in women who had discontinued use more than 10 years previously.

  6. Hereditary Ovarian Cancer: Not Only BRCA 1 and 2 Genes

    Directory of Open Access Journals (Sweden)

    Angela Toss

    2015-01-01

    Full Text Available More than one-fifth of ovarian tumors have hereditary susceptibility and, in about 65–85% of these cases, the genetic abnormality is a germline mutation in BRCA genes. Nevertheless, several other suppressor genes and oncogenes have been associated with hereditary ovarian cancers, including the mismatch repair (MMR genes in Lynch syndrome, the tumor suppressor gene, TP53, in the Li-Fraumeni syndrome, and several other genes involved in the double-strand breaks repair system, such as CHEK2, RAD51, BRIP1, and PALB2. The study of genetic discriminators and deregulated pathways involved in hereditary ovarian syndromes is relevant for the future development of molecular diagnostic strategies and targeted therapeutic approaches. The recent development and implementation of next-generation sequencing technologies have provided the opportunity to simultaneously analyze multiple cancer susceptibility genes, reduce the delay and costs, and optimize the molecular diagnosis of hereditary tumors. Particularly, the identification of mutations in ovarian cancer susceptibility genes in healthy women may result in a more personalized cancer risk management with tailored clinical and radiological surveillance, chemopreventive approaches, and/or prophylactic surgeries. On the other hand, for ovarian cancer patients, the identification of mutations may provide potential targets for biologic agents and guide treatment decision-making.

  7. The current status of PARP inhibitors in ovarian cancer.

    Science.gov (United States)

    McLachlan, Jennifer; George, Angela; Banerjee, Susana

    2016-10-13

    Recent advances in our understanding of the molecular biology of epithelial ovarian cancer have led to the development of a number of targeted therapies, including poly-ADP-ribose polymerase (PARP) inhibitors. PARP inhibitors are a novel class of therapeutic agents that target tumors with deficiencies in the homologous recombination DNA repair pathway. Early studies have shown significant efficacy for PARP inhibitors in patients with germline BRCA1/2 mutations. It has become evident that BRCA wild-type patients with other defects in the homologous recombination repair pathway benefit from this therapeutic approach. Importantly, companion homologous recombination deficiency scores are being developed to help guide the selection of patients most likely to gain clinical benefit from PARP inhibition. Olaparib, the first and most extensively investigated PARP inhibitor, is now licensed in Europe for maintenance treatment of patients with platinum-sensitive relapsed BRCA-mutated (germline or somatic) high-grade serous ovarian cancer who have responded to platinum-based chemotherapy. In the United States, olaparib is licensed for treatment of patients with germline BRCA-mutated ovarian cancer who have received 3 or more lines of chemotherapy. There are a number of other PARP inhibitors in late phase clinical development in ovarian cancer including rucaparib, niraparib, veliparib, and talazoparib. This review will focus on the current evidence for PARP inhibitors in ovarian cancer and discuss ongoing clinical trials and future research directions in this rapidly evolving area.

  8. IL-12 Expressing oncolytic herpes simplex virus promotes anti-tumor activity and immunologic control of metastatic ovarian cancer in mice.

    Science.gov (United States)

    Thomas, Eric D; Meza-Perez, Selene; Bevis, Kerri S; Randall, Troy D; Gillespie, G Yancey; Langford, Catherine; Alvarez, Ronald D

    2016-10-27

    Despite advances in surgical aggressiveness and conventional chemotherapy, ovarian cancer remains the most lethal cause of gynecologic cancer mortality; consequently there is a need for new therapeutic agents and innovative treatment paradigms for the treatment of ovarian cancer. Several studies have demonstrated that ovarian cancer is an immunogenic disease and immunotherapy represents a promising and novel approach that has not been completely evaluated in ovarian cancer. Our objective was to evaluate the anti-tumor activity of an oncolytic herpes simplex virus "armed" with murine interleukin-12 and its ability to elicit tumor-specific immune responses. We evaluated the ability of interleukin-12-expressing and control oncolytic herpes simplex virus to kill murine and human ovarian cancer cell lines in vitro. We also administered interleukin-12-expressing oncolytic herpes simplex virus to the peritoneal cavity of mice that had developed spontaneous, metastatic ovarian cancer and determined overall survival and tumor burden at 95 days. We used flow cytometry to quantify the tumor antigen-specific CD8(+) T cell response in the omentum and peritoneal cavity. All ovarian cancer cell lines demonstrated susceptibility to oncolytic herpes simplex virus in vitro. Compared to controls, mice treated with interleukin-12-expressing oncolytic herpes simplex virus demonstrated a more robust tumor antigen-specific CD8(+) T-cell immune response in the omentum (471.6 cells vs 33.1 cells; p = 0.02) and peritoneal cavity (962.3 cells vs 179.5 cells; p = 0.05). Compared to controls, mice treated with interleukin-12-expressing oncolytic herpes simplex virus were more likely to control ovarian cancer metastases (81.2 % vs 18.2 %; p = 0.008) and had a significantly longer overall survival (p = 0.02). Finally, five of 6 mice treated with interleukin-12-expressing oHSV had no evidence of metastatic tumor when euthanized at 6 months, compared to two of 4 mice treated

  9. Quality of life in ovarian cancer survivors: the influence of obesity

    NARCIS (Netherlands)

    Smits, A.; Lopes, A.; Das, N.; Bekkers, R.L.; Galaal, K.

    2015-01-01

    OBJECTIVE: In this study, we evaluated the effect of body mass index (BMI) on the quality of life of ovarian cancer survivors. METHODS: Women diagnosed with ovarian cancer at the Royal Cornwall Hospital Trust between January 2008 and May 2013 were identified. Ovarian cancer survivors were invited to

  10. 76 FR 22108 - Proposed Collection; Comment Request; Prostate, Lung, Colorectal and Ovarian Cancer Screening...

    Science.gov (United States)

    2011-04-20

    ..., Colorectal and Ovarian Cancer Screening Trial (PLCO) (NCI) SUMMARY: In compliance with the requirement of... Ovarian Cancer Screening Trial (PLCO) (NCI). Type of Information Collection Request: Revision (OMB : 0925... to determine if screening for prostate, lung, colorectal and ovarian cancer can reduce mortality...

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

    Directory of Open Access Journals (Sweden)

    Maria Szubert

    2016-07-01

    Full Text Available 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 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.

  12. Ovarian Cancer Screening Method Fails to Reduce Deaths from the Disease | Division of Cancer Prevention

    Science.gov (United States)

    New results from the NCI-sponsored Prostate, Lung, Colorectal and Ovarian (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. |

  13. Reprogramming antitumor immunity against chemoresistant ovarian cancer by a CXCR4 antagonist-armed viral oncotherapy

    Directory of Open Access Journals (Sweden)

    Marcin P Komorowski

    2016-01-01

    Full Text Available Ovarian cancer remains the most lethal gynecologic malignancy owing to late detection, intrinsic and acquired chemoresistance, and remarkable heterogeneity. Here, we explored approaches to inhibit metastatic growth of murine and human ovarian tumor variants resistant to paclitaxel and carboplatin by oncolytic vaccinia virus expressing a CXCR4 antagonist to target the CXCL12 chemokine/CXCR4 receptor signaling axis alone or in combination with doxorubicin. The resistant variants exhibited augmented expression of the hyaluronan receptor CD44 and CXCR4 along with elevated Akt and ERK1/2 activation and displayed an increased susceptibility to viral infection compared with the parental counterparts. The infected cultures were more sensitive to doxorubicin-mediated killing both in vitro and in tumor-challenged mice. Mechanistically, the combination treatment increased apoptosis and phagocytosis of tumor material by dendritic cells associated with induction of antitumor immunity. Targeting syngeneic tumors with this regimen increased intratumoral infiltration of antitumor CD8+ T cells. This was further enhanced by reducing the immunosuppressive network by the virally-delivered CXCR4 antagonist, which augmented antitumor immune responses and led to tumor-free survival. Our results define novel strategies for treatment of drug-resistant ovarian cancer that increase immunogenic cell death and reverse the immunosuppressive tumor microenvironment, culminating in antitumor immune responses that control metastatic tumor growth.

  14. 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

  15. 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.

  16. Oxytocin modulates the onset of murine parturition by competing ovarian and uterine effects.

    Science.gov (United States)

    Imamura, T; Luedke, C E; Vogt, S K; Muglia, L J

    2000-09-01

    Recent analysis of mice deficient in both oxytocin (OT) and cyclooxygenase-1 has shown that OT exerts significant effects on both the ovarian corpus luteum and the uterine myometrium during pregnancy. To better define the roles of OT during pregnancy, we evaluated OT action and OT receptor regulation in wild-type and OT-deficient knockout (KO) mice. Continuous infusion of OT revealed that OT can either delay labor at low doses or initiate preterm labor at high doses. The infusion rates of OT necessary for these effects were reduced in OT KO mice. The dose of OT that delayed labor also delayed the normal decrease in plasma progesterone late in gestation, implicating a primary effect on the corpus luteum. Consistent with this hypothesis, luteal OT receptor expression exceeded that of the myometrium until luteolysis occurred. We propose that the downregulation of OT receptors in the corpus luteum and induction of OT receptors in the myometrium serve to shift the predominant consequence of OT action during murine pregnancy from labor inhibition to labor promotion.

  17. Symptom interpretation and health care seeking in ovarian cancer

    DEFF Research Database (Denmark)

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

    2011-01-01

    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......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...

  18. Future directions in the management of ovarian cancer.

    Science.gov (United States)

    Disis, Mary L; Rivkin, Saul

    2003-08-01

    As investigators at the bench define the oncogenic pathways involved in ovarian cancer growth and invasion, clinical scientists will develop therapies to target these important pathways. The approach to the treatment of ovarian cancer will change to focus on strategies designed to eliminate minimal residual disease after primary therapy and in this way cure the disease. Concepts of consolidation after standard adjuvant chemotherapy and maintenance regimens will start to be evaluated for clinical efficacy. In addition, the focus on recurrent disease may change from repeated cytotoxic approaches to regimens chosen to prevent invasion or the development of drug resistance, changing the approach to ovarian cancer recurrence to a treatment plan of managing a chronic, but not imminently terminal, disease.

  19. Role of the Microenvironment in Ovarian Cancer Stem Cell Maintenance

    Science.gov (United States)

    Pasquier, Jennifer; Rafii, Arash

    2013-01-01

    Despite recent progresses in cancer therapy and increased knowledge in cancer biology, ovarian cancer remains a challenging condition. Among the latest concepts developed in cancer biology, cancer stem cells and the role of microenvironment in tumor progression seem to be related. Indeed, cancer stem cells have been described in several solid tumors including ovarian cancers. These particular cells have the ability to self-renew and reconstitute a heterogeneous tumor. They are characterized by specific surface markers and display resistance to therapeutic regimens. During development, specific molecular cues from the tumor microenvironment can play a role in maintaining and expanding stemness of cancer cells. The tumor stroma contains several compartments: cellular component, cytokine network, and extracellular matrix. These different compartments interact to form a permissive niche for the cancer stem cells. Understanding the molecular cues underlying this crosstalk will allow the design of new therapeutic regimens targeting the niche. In this paper, we will discuss the mechanisms implicated in the interaction between ovarian cancer stem cells and their microenvironment. PMID:23484135

  20. Chemokine Receptors in Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Goda G. Muralidhar

    2013-12-01

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

  1. Aurora-A Oncogene in Human Ovarian Cancer

    Science.gov (United States)

    2006-11-01

    in Human Ovarian Cancer 5b. GRANT NUMBER W81XWH-05-1-0021 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER Jin Q. Cheng, M.D...this project : 1) examine the clinicalpathological significance and the mechanism of Aurora-A overexpression/activation in ovarian cancer; 2) determine...kinase is required to localize D-TACC to centro- somes and to regulate astral microtubules. J Cell Biol 2002;156:437–51. 33. Castro A, Mandart E, Lorca T

  2. 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.

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

    OpenAIRE

    Francesca De Felice; Claudia Marchetti; Innocenza Palaia; Daniela Musio; Ludovico Muzii; Vincenzo Tombolini; Pierluigi Benedetti Panici

    2015-01-01

    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 can...

  4. Cost-effectiveness of opportunistic salpingectomy for ovarian cancer prevention.

    Science.gov (United States)

    Dilley, Sarah E; Havrilesky, Laura J; Bakkum-Gamez, Jamie; Cohn, David E; Michael Straughn, J; Caughey, Aaron B; Rodriguez, Maria I

    2017-08-01

    Data suggesting a link between the fallopian tube and ovarian cancer have led to an increase in rates of salpingectomy at the time of pelvic surgery, a practice known as opportunistic salpingectomy (OS). However, the potential benefits, risks and costs for this new practice are not well established. Our objective was to assess the cost-effectiveness of opportunistic salpingectomy at the time of laparoscopic permanent contraception or hysterectomy for benign indications. We created two models to compare the cost-effectiveness of salpingectomy versus usual care. The hypothetical study population is 50,000 women aged 45 undergoing laparoscopic hysterectomy with ovarian preservation for benign indications, and 300,000 women aged 35 undergoing laparoscopic permanent contraception. SEER data were used for probabilities of ovarian cancer cases and deaths. The ovarian cancer risk reduction, complication rates, utilities and associated costs were obtained from published literature. Sensitivity analyses and Monte Carlo simulation were performed, and incremental cost-effectiveness ratios (ICERs) were calculated to determine the cost per quality adjusted life year (QALY) gained. In the laparoscopic hysterectomy cohort, OS is cost saving and would yield $23.9 million in health care dollars saved. In the laparoscopic permanent contraception cohort, OS is cost-effective with an ICER of $31,432/QALY compared to tubal ligation, and remains cost-effective as long as it reduces ovarian cancer risk by 54%. Monte Carlo simulation demonstrated cost-effectiveness with hysterectomy and permanent contraception in 62.3% and 55% of trials, respectively. Opportunistic salpingectomy for low-risk women undergoing pelvic surgery may be a cost-effective strategy for decreasing ovarian cancer risk at time of hysterectomy or permanent contraception. In our model, salpingectomy was cost-effective with both procedures, but the advantage greater at time of hysterectomy. Copyright © 2017. Published by

  5. Tumor-Selective Response to Antibody-Mediated Targeting of αvβ3 Integrin in Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Charles N. Landen

    2008-11-01

    Full Text Available The αvβ3 integrin is expressed on proliferating endothelial cells and some cancer cells, but its expression on ovarian cancer cells and its potential as a therapeutic target are unknown. In this study, expression of the αvβ3 integrin on ovarian cancer cell lines and murine endothelial cells was tested, and the effect of a fully humanized monoclonal antibody against αvβ3, Abegrin (etaracizumab, on cell invasion, viability, tumor growth, and the Akt pathway were examined in vitro and in vivo. We found that etaracizumab recognizes αvβ3 on the ovarian cancer cell lines SKOV3ip1, HeyA8, and A2780ip2 (at low levels but not on murine endothelial cells. Etaracizumab treatment decreased ovarian cancer proliferation and invasion. In vivo, tumor-bearing mice treated with etaracizumab alone gave variable results. There was no effect on A2780ip2 growth, but a 36% to 49% tumor weight reduction in the SKOV3ip1 and HeyA8 models was found (P < .05. However, combined etaracizumab and paclitaxel was superior to paclitaxel in the SKOV3ip1 and A2780ip2 models (by 51–73%, P < .001 but not in the HeyA8 model. Treatment with etaracizumab was then noted to decrease p-Akt and p-mTOR in SKOV3ip1, but not in HeyA8, which is Akt-independent. Tumors resected after therapy showed that etaracizumab treatment reduced the proliferating cell nuclear antigen index but not microvessel density. This study identifies tumor cell αvβ3 integrin as an attractive target and defines the Akt pathway as a predictor of response to function-blocking antibody.

  6. 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

  7. Suppression of cancer stemness p21-regulating mRNA and microRNA signatures in recurrent ovarian cancer patient samples

    Directory of Open Access Journals (Sweden)

    Gallagher Michael F

    2012-01-01

    Full Text Available Abstract Background Malignant ovarian disease is characterised by high rates of mortality due to high rates of recurrent chemoresistant disease. Anecdotal evidence indicates this may be due to chemoresistant properties of cancer stem cells (CSCs. However, our understanding of the role of CSCs in recurrent ovarian disease remains sparse. In this study we used gene microarrays and meta-analysis of our previously published microRNA (miRNA data to assess the involvement of cancer stemness signatures in recurrent ovarian disease. Methods Microarray analysis was used to characterise early regulation events in an embryonal carcinoma (EC model of cancer stemness. This was then compared to our previously published microarray data from a study of primary versus recurrent ovarian disease. In parallel, meta-analysis was used to identify cancer stemness miRNA signatures in tumor patient samples. Results Microarray analysis demonstrated a 90% difference between gene expression events involved in early regulation of differentiation in murine EC (mEC and embryonic stem (mES cells. This contrasts the known parallels between mEC and mES cells in the undifferentiated and well-differentiated states. Genelist comparisons identified a cancer stemness signature set of genes in primary versus recurrent data, a subset of which are known p53-p21 regulators. This signature is present in primary and recurrent or in primary alone but essentially never in recurrent tumors specifically. Meta-analysis of miRNA expression showed a much stronger cancer stemness signature within tumor samples. This miRNA signature again related to p53-p21 regulation and was expressed prominently in recurrent tumors. Our data indicate that the regulation of p53-p21 in ovarian cancer involves, at least partially, a cancer stemness component. Conclusion We present a p53-p21 cancer stemness signature model for ovarian cancer. We propose that this may, at least partially, differentially regulate the p

  8. Suppression of Cancer Stemness p21-regulating mRNA and microRNA Signatures in Recurrent Ovarian Cancer Patient Samples

    LENUS (Irish Health Repository)

    Gallagher, Michael F

    2012-01-19

    Abstract Background Malignant ovarian disease is characterised by high rates of mortality due to high rates of recurrent chemoresistant disease. Anecdotal evidence indicates this may be due to chemoresistant properties of cancer stem cells (CSCs). However, our understanding of the role of CSCs in recurrent ovarian disease remains sparse. In this study we used gene microarrays and meta-analysis of our previously published microRNA (miRNA) data to assess the involvement of cancer stemness signatures in recurrent ovarian disease. Methods Microarray analysis was used to characterise early regulation events in an embryonal carcinoma (EC) model of cancer stemness. This was then compared to our previously published microarray data from a study of primary versus recurrent ovarian disease. In parallel, meta-analysis was used to identify cancer stemness miRNA signatures in tumor patient samples. Results Microarray analysis demonstrated a 90% difference between gene expression events involved in early regulation of differentiation in murine EC (mEC) and embryonic stem (mES) cells. This contrasts the known parallels between mEC and mES cells in the undifferentiated and well-differentiated states. Genelist comparisons identified a cancer stemness signature set of genes in primary versus recurrent data, a subset of which are known p53-p21 regulators. This signature is present in primary and recurrent or in primary alone but essentially never in recurrent tumors specifically. Meta-analysis of miRNA expression showed a much stronger cancer stemness signature within tumor samples. This miRNA signature again related to p53-p21 regulation and was expressed prominently in recurrent tumors. Our data indicate that the regulation of p53-p21 in ovarian cancer involves, at least partially, a cancer stemness component. Conclusion We present a p53-p21 cancer stemness signature model for ovarian cancer. We propose that this may, at least partially, differentially regulate the p53-p21

  9. 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...... was not associated with risk. These data provide suggestive evidence that the rs2295190 T allele, or another allele in linkage disequilibrium with it, may be associated with increased risk of invasive ovarian cancer....

  10. Association between invasive ovarian cancer susceptibility and 11 best candidate SNPs from breast cancer genome-wide association study

    DEFF Research Database (Denmark)

    Song, Honglin; Ramus, Susan J; Kjaer, Susanne Krüger;

    2009-01-01

    , three SNPs (rs2107425 in MRPL23, rs7313833 in PTHLH, rs3803662 in TNRC9) were weakly associated with ovarian cancer risk and one SNP (rs4954956 in NXPH2) was associated with serous ovarian cancer in non-Hispanic white subjects (P-trend ....01-1.13, P-trend = 0.02 for all types of ovarian cancer and OR 1.14 95% CI 1.07-1.22, P-trend = 0.00017 for serous ovarian cancer]. In conclusion, we found that rs4954956 was associated with increased ovarian cancer risk, particularly for serous ovarian cancer. However, none of the six confirmed breast...... cancer susceptibility variants we tested was associated with ovarian cancer risk. Further work will be needed to identify the causal variant associated with rs4954956 or elucidate its function....

  11. Nuclear Factor-Kappa B Activity in the Host-Tumor Microenvironment of Ovarian Cancer

    Science.gov (United States)

    2014-10-01

    Holson EB, Khabele D, Hiebert SW. HDAC3 is essential for the maintenance of chromatin structure and genome stability. Cancer Cell 18: 436-47, 2010... aspirin (ASA) in COX-1 positive ovarian cancer cells through augmentation of p21. Cancer Biol. Ther. 9: 928-35, 2010. PMID: 20404564 11. Wilson AJ, Chueh...elucidate effects of disrupting activity of COX-1 in ovarian cancer cells and platelets via aspirin on progression of ovarian cancer. The ability of

  12. Aspirin and P2Y12 inhibition attenuate platelet-induced ovarian cancer cell invasion.

    LENUS (Irish Health Repository)

    Cooke, Niamh M

    2015-09-09

    Platelet-cancer cell interactions play a key role in successful haematogenous metastasis. Disseminated malignancy is the leading cause of death among ovarian cancer patients. It is unknown why different ovarian cancers have different metastatic phenotypes. To investigate if platelet-cancer cell interactions play a role, we characterized the response of ovarian cancer cell lines to platelets both functionally and at a molecular level.

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

    Directory of Open Access Journals (Sweden)

    Liu Jinsong

    2005-02-01

    Full Text Available 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 with normal ovarian tissues. Furthermore, IGFBP2 was significantly overexpressed in invasive serous ovarian carcinomas compared with borderline serous ovarian tumors. To test whether increased IGFBP2 contributes to the highly invasive nature of ovarian cancer cells, we generated IGFBP2-overexpressing cells from an SKOV3 ovarian cancer cell line, which has a very low level of endogenous IGFBP2. A Matrigel invasion assay showed that these IGFBP2-overexpressing cells were more invasive than the control cells. We then designed small interference RNA (siRNA molecules that attenuated IGFBP2 expression in PA-1 ovarian cancer cells, which have a high level of endogenous IGFBP2. The Matrigel invasion assay showed that the attenuation of IGFBP2 expression indeed decreased the invasiveness of PA-1 cells. Conclusions We therefore showed that IGFBP2 enhances the invasion capacity of ovarian cancer cells. Blockage of IGFBP2 may thus constitute a viable strategy for targeted cancer therapy.

  14. 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.

  15. 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

  16. Identification of ovarian cancer symptoms in health insurance claims data.

    Science.gov (United States)

    Devlin, Sean M; Diehr, Paula H; Andersen, M Robyn; Goff, Barbara A; Tyree, Patrick T; Lafferty, William E

    2010-03-01

    Women with ovarian cancer have reported abdominal/pelvic pain, bloating, difficulty eating or feeling full quickly, and urinary frequency/urgency prior to diagnosis. We explored these findings in a general population using a dataset of insured women aged 40-64 and investigated the potential effectiveness of a routine review of claims data as a prescreen to identify women at high risk for ovarian cancer. Data from a large Washington State health insurer were merged with the Seattle-Puget Sound Surveillance, Epidemiology and End Results (SEER) cancer registry for 2000-2004. We estimated the prevalence of symptoms in the 36 months prior to diagnosis for early and late-stage ovarian cancer cases and for two comparison groups. The potential performance of a passive screener that would flag women with two or more visits for any of the symptoms in the previous 2-month period was examined. Of the 223,903 insured women, 161 had incident cases of ovarian cancer. Both early and late-stage patients had a higher prevalence of abdominal/pelvic pain and bloating than the comparison groups, primarily in the 3 months before diagnosis. The passive screener had a sensitivity of 0.31 and specificity of 0.83 and usually identified women right before diagnosis. Assuming an average cost of $500 per false positive, the screener would be considered cost-effective if the true positives had an average increase of 8.5 years of life expectancy. These results support previous findings that ovarian cancer symptoms were reported in health insurance claims and were more prevalent before diagnosis, but the symptoms may occur too close to the diagnosis date to provide useful diagnostic information. The passive screening approach should be reevaluated in the future using electronic medical records; if found to be effective, the method may be potentially useful for other incident diseases.

  17. Genital powder exposure and the risk of epithelial ovarian cancer

    Science.gov (United States)

    Rosenblatt, Karin A.; Weiss, Noel S.; Cushing-Haugen, Kara L.; Wicklund, Kristine G.; Rossing, Mary Anne

    2011-01-01

    Background We conducted a population-based, case–control study to examine the association between the use of genital powder and ovarian cancer risk, including measures of extent and timing of exposure. We also assessed the relationship of powder use with risk of disease subtypes according to histology and degree of malignancy. Methods Information was collected during in-person interviews with 812 women with epithelial ovarian cancer diagnosed in western Washington State from 2002 to 2005 and 1,313 controls. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Results Overall, the perineal use of powder after bathing was associated with a slightly increased ovarian cancer risk (OR = 1.27, 95% CI: 0.97–1.66), which was most evident among women with borderline tumors (OR = 1.55, 95% CI: 1.02–2.37). We noted no clear pattern of risk increase on the basis of the extent of use, assessed as years in which powder was used, or as lifetime number of applications for invasive or borderline tumors, or their histologic subtypes. There was no alteration in the risk of ovarian cancer associated with other types of powder exposure (e.g., on sanitary napkins or diaphragms). Conclusions The International Agency for Research on Cancer has designated perineal exposure to talc (via the application of genital powders) as a possible carcinogen in women. A modest association of ovarian cancer with this exposure was seen in our study and in some previous ones, but that association generally has not been consistent within or among studies. Therefore, no stronger adjective than “possible” appears warranted at this time. PMID:21516319

  18. 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

  19. 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.

  20. 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

  1. Prognostic relevance of acquired uniparental disomy in serous ovarian cancer

    NARCIS (Netherlands)

    M. Tuna (Musaffe); Z. Ju (Zhenlin); M. Smid (Marcel); C.I. Amos (Christopher I.); G.B. Mills (Gordon B.)

    2015-01-01

    textabstractBACKGROUND: Acquired uniparental disomy (aUPD) can lead to homozygosity for tumor suppressor genes or oncogenes. Our purpose is to determine the frequency and profile aUPD regions in serous ovarian cancer (SOC) and investigated the association of aUPD with clinical features and patient o

  2. Prognostic relevance of acquired uniparental disomy in serous ovarian cancer

    NARCIS (Netherlands)

    M. Tuna (Musaffe); Z. Ju (Zhenlin); M. Smid (Marcel); W. Amos; G. Mills

    2015-01-01

    textabstractBackground: Acquired uniparental disomy (aUPD) can lead to homozygosity for tumor suppressor genes or oncogenes. Our purpose is to determine the frequency and profile aUPD regions in serous ovarian cancer (SOC) and investigated the association of aUPD with clinical features and patient o

  3. 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.

  4. 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

  5. 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.

  6. 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

  7. 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...

  8. Ovarian cancer and talc: a case-control study.

    Science.gov (United States)

    Cramer, D W; Welch, W R; Scully, R E; Wojciechowski, C A

    1982-07-15

    Opportunities for genital exposure to talc were assessed in 215 white females with epithelial ovarian cancers and in 215 control women from the general population matched by age, race, and residence. Ninety-two (42.8%) cases regularly used talc either as a dusting powder on the perineum or on sanitary napkins compared with 61 (28.4%) controls. Adjusted for parity and menopausal status, this difference yielded a relative risk of 1.92 (P less than 0.003) for ovarian cancer associated with these practices. Women who had regularly engaged in both practices had an adjusted relative risk of 3.28 (P less than 0.001) compared to women with neither exposure. This provides some support for an association between talc and ovarian cancer hypothesized because of the similarity of ovarian cancer to mesotheliomas and the chemical relation of talc to asbestos, a known cause of mesotheliomas. The authors also investigated opportunities for potential talc exposure from rubber products such as condoms or diaphragms or from pelvic surgery. No significant differences were noted between cases and controls in these exposures, although the intensity of talc exposure from these sources was likely affected by variables not assessed in this study.

  9. 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...

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

    NARCIS (Netherlands)

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

    2008-01-01

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

  11. 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...

  12. 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

  13. 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.

  14. 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...

  15. Obesity and survival among women with ovarian cancer

    DEFF Research Database (Denmark)

    Nagle, C M; Dixon, S C; Jensen, A.

    2015-01-01

    BACKGROUND: Observational studies have reported a modest association between obesity and risk of ovarian cancer; however, whether it is also associated with survival and whether this association varies for the different histologic subtypes are not clear. We undertook an international collaborativ...

  16. Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer

    DEFF Research Database (Denmark)

    Mirza, Mansoor R; Monk, Bradley J; Herrstedt, Jørn

    2016-01-01

    Background Niraparib is an oral poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) 1/2 inhibitor that has shown clinical activity in patients with ovarian cancer. We sought to evaluate the efficacy of niraparib versus placebo as maintenance treatment for patients with platinum-sensitive, ...

  17. 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?

  18. Overcoming cisplatin resistance of ovarian cancer cells by targeting HIF-1-regulated cancer metabolism.

    Science.gov (United States)

    Ai, Zhihong; Lu, Yang; Qiu, Songbo; Fan, Zhen

    2016-04-01

    Cisplatin is currently one of the most effective chemotherapeutic drugs used for treating ovarian cancer; however, resistance to cisplatin is common. In this study, we explored an experimental strategy for overcoming cisplatin resistance of human ovarian cancer from the new perspective of cancer cell metabolism. By using two pairs of genetically matched cisplatin-sensitive and cisplatin-resistant ovarian cancer cell lines, we tested the hypothesis that downregulating hypoxia-inducible factor-1 (HIF-1), which regulates metabolic enzymes involved in glycolysis, is a promising strategy for overcoming cisplatin resistance of human ovarian cancer cells. We found that cisplatin downregulated the level of the regulatable α subunit of HIF-1, HIF-1α, in cisplatin-sensitive ovarian cancer cells through enhancing HIF-1α degradation but did not downregulate HIF-1α in their cisplatin-resistant counterparts. Overexpression of a degradation-resistant HIF-1α (HIF-1α ΔODD) reduced cisplatin-induced apoptosis in cisplatin-sensitive cells, whereas genetic knockdown of HIF-1α or pharmacological promotion of HIF-1α degradation enhanced response to cisplatin in both cisplatin-sensitive and cisplatin-resistant ovarian cancer cells. We further demonstrated that knockdown of HIF-1α improved the response of cisplatin-resistant ovarian cancer cells to cisplatin by redirecting the aerobic glycolysis in the resistant cancer cells toward mitochondrial oxidative phosphorylation, leading to cell death through overproduction of reactive oxygen species. Our findings suggest that the HIF-1α-regulated cancer metabolism pathway could be a novel target for overcoming cisplatin resistance in ovarian cancer.

  19. Pro-lipogenic Action of Lysophosphatidic Acid in Ovarian Cancer

    Science.gov (United States)

    2012-07-01

    currently testing appropriate doses and kinetics for further analysis in ovarian cancer cell lines. 1.3 Assessment of the effects on lipogenic...Triacylglycerols (TAG) and Phospholipids— TAGand phospholipids were extracted and quantified with the EnzyChrom triglyceride assay kit and the...most commonly seen in almost all cancer types examined (16, 56–58). There is also strong evidence from xenograft mouse models and transgenic mice that

  20. Blood type, ABO genetic variants, and ovarian cancer survival.

    Science.gov (United States)

    Cozzi, Gabriella D; Levinson, Rebecca T; Toole, Hilary; Snyder, Malcolm-Robert; Deng, Angie; Crispens, Marta A; Khabele, Dineo; Beeghly-Fadiel, Alicia

    2017-01-01

    Blood type A and the A1 allele have been associated with increased ovarian cancer risk. With only two small studies published to date, evidence for an association between ABO blood type and ovarian cancer survival is limited. We conducted a retrospective cohort study of Tumor Registry confirmed ovarian cancer cases from the Vanderbilt University Medical Center with blood type from linked laboratory reports and ABO variants from linked Illumina Exome BeadChip data. Associations with overall survival (OS) were quantified by hazard ratios (HR) and confidence intervals (CI) from proportional hazards regression models; covariates included age, race, stage, grade, histologic subtype, and year of diagnosis. ABO phenotype (N = 694) and/or genotype (N = 154) data were available for 713 predominantly Caucasian (89.3%) cases. In multivariable models, blood type A had significantly better OS compared to either O (HR: 0.75, 95% CI: 0.60-0.93) or all non-A (HR: 0.77, 95% CI: 0.63-0.94) cases. Similarly, missense rs1053878 minor allele carriers (A2) had better OS (HR: 0.50, 95% CI: 0.25-0.99). Among Caucasians, this phenotype association was strengthened, but the genotype association was attenuated; instead, four variants sharing moderate linkage disequilibrium with the O variant were associated with better OS (HR: 0.62, 95% CI: 0.39-0.99) in unadjusted models. Blood type A was significantly associated with longer ovarian cancer survival in the largest such study to date. This finding was supported by genetic analysis, which implicated the A2 allele, although O related variants also had suggestive associations. Further research on ABO and ovarian cancer survival is warranted.

  1. The prognostic significance of thrombocytosis in ovarian cancer.

    Science.gov (United States)

    Słabuszewska-Jóźwiak, Aneta; Dmoch-Gajzlerska, Ewa; Kozakiewicz, Barbara; Jakiel, Grzegorz

    2015-01-01

    Ovarian cancer makes up 25-30% of all cases of cancers of the female genital tract. It has the highest mortality rate of any condition in oncological gynaecology. Early diagnosis is associated with a favourable 5-year survival prognosis. Many solid tumours have been detected with concomitant thrombocytosis. The tumour cell-induced platelet aggregation is a result of a direct integration of tumour cells with blood platelets. The aim of the present paper is an evaluation of platelet count as a prognostic parameter for ovarian cancer. Between 2000 - 2005, 349 patients with ovarian tumour (aged 12 - 88-years-old) underwent primary surgical treatment at a clinic. Ninety-seven patients with ovarian carcinomas underwent chemotherapy in the Oncology Centre. The control group comprised 252 women diagnosed with a histopathological lesion of mild intensity, whereas the cancer group constituted 97 women with a histopathologically-diagnosed malignant neoplasm. Thrombocytopaenia was assumed with a platelet count below 150G/L and thrombocythaemia at 350G/L and higher. Thrombocytosis often coincides with ascites and the cytoreduction decreases platelet count. There is a positive correlation between platelet count and tumour grading. Thrombocytosis was more frequently found in high grade tumours. There is also a positive correlation between platelet count and tumour stage according the International Federation of Gynaecology and Obstetrics (FIGO). Thrombocytosis was more frequently found in stage III and IV cancers. Patients with co-occurring thrombocytosis were found to have shorter survival periods and shorter time free from disease. This seems to give grounds for measuring platelet count before the primary surgical intervention, and suggests that the platelet count should be included in the panel of prognostic factors for patients with ovarian tumours.

  2. 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

  3. 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

  4. Preemptive Approach to Improving Survival in Epithelial Ovarian Cancer

    Science.gov (United States)

    2012-06-01

    2012.06.017 U N C O R R E C T E D P R O O F 76 human papilloma virus screening to examine cell lines of purported 77 ovarian and endometrial origins...profileQ4 from the American Type Culture Collection. HPV: human papilloma virus status (+: positive;−: negative). MCF-7 breast cancer cells reference STR...j.ygyno.2012.06.017 U N C O R R E C T E D P R O O F 76 human papilloma virus screening to examine cell lines of purported 77 ovarian and endometrial

  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

    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. 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

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  8. 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.

  9. 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.

  10. Significance of preoperative thrombocytosis in epithelial ovarian cancer

    Directory of Open Access Journals (Sweden)

    Crasta Julian

    2010-01-01

    Full Text Available Background: Reactive thrombocytosis is reported in a variety of solid tumors. A few studies have documented preoperative thrombocytosis in ovarian cancer and identified it as a marker of aggressive tumor biology. Aim: To study the incidence of preoperative thrombocytosis (platelets greater than 400x10 in epithelial ovarian cancer and its association with other clinicopathologic factors. Materials and Methods: Sixty-five patients with invasive ovarian epithelial cancer were retrospectively reviewed and analyzed for the association preoperative thrombocytosis with other clinical and histopathological prognostic factors. Means were analyzed by Student′s t test; proportions were determined by Chi-square analysis. Results: Twenty of 65 (37.5% patients had thrombocytosis at primary diagnosis. Patients with preoperative thrombocytosis were found to have lower hemoglobin (P < 0.0002, more advanced stage disease (P < 0.05 and higher grade tumors (P < 0.02. Patients with thrombocytosis had greater likelihood of subpotimal cytoreduction. Conclusions: Preoperative thrombocytosis is a frequent finding in ovarian carcinomas and their association with advanced stage disease and higher grade denotes that platelets play a role in the tumor growth and progression.

  11. Therapeutic Inhibitors of LIN28/let-7 Pathway in Ovarian Cancer

    Science.gov (United States)

    2015-09-01

    AWARD NUMBER: W81XWH-14-1-0138 TITLE: Therapeutic Inhibitors of LIN28/let-7 Pathway in Ovarian Cancer PRINCIPAL INVESTIGATOR: John P. Hagan...2015 4. TITLE AND SUBTITLE Therapeutic Inhibitors of LIN28/let-7 Pathway in Ovarian Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1...prognosis in multiple cancer types, including ovarian. Silent in almost all adult cells, the Lin28/let-7 pathway is implicated directly in cancer stem

  12. Prognostic significance of discoidin domain receptor 2 (DDR2) expression in ovarian cancer

    OpenAIRE

    Fan, Yi; Xu, Zhe; Fan, Jin; Huang, Liu; Ye, Ming; Shi, Kun; Huang, Zheng; Liu, Yaqiong; He, Langchi; Huang, Jiezhen; Wang, Yibin; Li, Qiufeng

    2016-01-01

    Increasing evidence has suggested that discoidin domain receptor 2 (DDR2) plays an important role in cancer development and metastasis. However, the correlation between DDR2 expression and clinical outcome in ovarian cancer has not been investigated. In this study, DDR2 expression was examined by Real-time PCR in surgically resected ovarian cancer and normal ovary tissues. Besides, DDR2 expression was analyzed immunohistochemically in 103 ovarian cancer patients, and the correlation between D...

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. Lipopolysaccharide reduces the primordial follicle pool in the bovine ovarian cortex ex vivo and in the murine ovary in vivo.

    Science.gov (United States)

    Bromfield, John J; Sheldon, I Martin

    2013-04-01

    Infections of the uterus or mammary gland with Gram-negative bacteria cause infertility in cattle, not only during disease but also for some time afterward. Even though these infections are in organs distant from the ovary, metritis and mastitis perturb antral follicle development and function in vivo. Although granulosa cells from antral follicles express toll-like receptor 4 (TLR4), and detect and mount an inflammatory response to lipopolysaccharide (LPS) from Gram-negative bacteria, it is not known whether LPS impacts preantral follicle development. The present study tested the hypothesis that LPS perturbs the development of primordial ovarian follicles. Exposure of bovine ovarian cortex ex vivo to LPS reduced the primordial follicle pool associated with increased primordial follicle activation. Ovarian cortex culture supernatants accumulated the inflammatory mediators IL-1beta, IL-6, and IL-8 in an LPS concentration-dependent manner. In addition, LPS exposure modulated key intracellular regulators of follicle activation with loss of the primordial follicle PTEN and cytoplasmic translocation of FOXO3. Acute exposure of mice in vivo to LPS also reduced the primordial follicle pool associated with increased follicle atresia. The increased follicle atresia was TLR4-dependent as Tlr4-deficient mice were insensitive to LPS-mediated follicle atresia. However, LPS did not affect the diameter of individually cultured bovine secondary follicles or their enclosed oocytes. In conclusion, LPS reduced the primordial ovarian follicle pool in the bovine ovarian cortex ex vivo and in the murine ovary in vivo. These observations provide an insight into how bacterial infections distant from the ovary have long term effects on fertility.

  18. 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.

  19. 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

  20. CRISPR/Cas9-Mediated Trp53 and Brca2 Knockout to Generate Improved Murine Models of Ovarian High-Grade Serous Carcinoma.

    Science.gov (United States)

    Walton, Josephine; Blagih, Julianna; Ennis, Darren; Leung, Elaine; Dowson, Suzanne; Farquharson, Malcolm; Tookman, Laura A; Orange, Clare; Athineos, Dimitris; Mason, Susan; Stevenson, David; Blyth, Karen; Strathdee, Douglas; Balkwill, Frances R; Vousden, Karen; Lockley, Michelle; McNeish, Iain A

    2016-10-15

    There is a need for transplantable murine models of ovarian high-grade serous carcinoma (HGSC) with regard to mutations in the human disease to assist investigations of the relationships between tumor genotype, chemotherapy response, and immune microenvironment. In addressing this need, we performed whole-exome sequencing of ID8, the most widely used transplantable model of ovarian cancer, covering 194,000 exomes at a mean depth of 400× with 90% exons sequenced >50×. We found no functional mutations in genes characteristic of HGSC (Trp53, Brca1, Brca2, Nf1, and Rb1), and p53 remained transcriptionally active. Homologous recombination in ID8 remained intact in functional assays. Further, we found no mutations typical of clear cell carcinoma (Arid1a, Pik3ca), low-grade serous carcinoma (Braf), endometrioid (Ctnnb1), or mucinous (Kras) carcinomas. Using CRISPR/Cas9 gene editing, we modeled HGSC by generating novel ID8 derivatives that harbored single (Trp53(-/-)) or double (Trp53(-/-);Brca2(-/-)) suppressor gene deletions. In these mutants, loss of p53 alone was sufficient to increase the growth rate of orthotopic tumors with significant effects observed on the immune microenvironment. Specifically, p53 loss increased expression of the myeloid attractant CCL2 and promoted the infiltration of immunosuppressive myeloid cell populations into primary tumors and their ascites. In Trp53(-/-);Brca2(-/-) mutant cells, we documented a relative increase in sensitivity to the PARP inhibitor rucaparib and slower orthotopic tumor growth compared with Trp53(-/-) cells, with an appearance of intratumoral tertiary lymphoid structures rich in CD3(+) T cells. This work validates new CRISPR-generated models of HGSC to investigate its biology and promote mechanism-based therapeutics discovery. Cancer Res; 76(20); 6118-29. ©2016 AACR. ©2016 American Association for Cancer Research.

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

    Institute of Scientific and Technical Information of China (English)

    程琪辉; 张喜平; 曾小澜

    2003-01-01

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

  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. Angiogenesis-Related Pathways in the Pathogenesis of Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Aristotle Bamias

    2013-07-01

    Full Text Available Ovarian Cancer represents the most fatal type of gynecological malignancies. A number of processes are involved in the pathogenesis of ovarian cancer, especially within the tumor microenvironment. Angiogenesis represents a hallmark phenomenon in cancer, and it is responsible for tumor spread and metastasis in ovarian cancer, among other tumor types, as it leads to new blood vessel formation. In recent years angiogenesis has been given considerable attention in order to identify targets for developing effective anti-tumor therapies. Growth factors have been identified to play key roles in driving angiogenesis and, thus, the formation of new blood vessels that assist in “feeding” cancer. Such molecules include the vascular endothelial growth factor (VEGF, the platelet derived growth factor (PDGF, the fibroblast growth factor (FGF, and the angiopoietin/Tie2 receptor complex. These proteins are key players in complex molecular pathways within the tumor cell and they have been in the spotlight of the development of anti-angiogenic molecules that may act as stand-alone therapeutics, or in concert with standard treatment regimes such as chemotherapy. The pathways involved in angiogenesis and molecules that have been developed in order to combat angiogenesis are described in this paper.

  4. Perineal Talc Use and Ovarian Cancer: A Critical Review

    Science.gov (United States)

    Muscat, Joshua E.; Huncharek, Michael S.

    2013-01-01

    Talc, like asbestos, is a silicate that has been studied in relation to cancer risk. Several studies conducted over the past 25 years found an association between perineal talc powders and ovarian cancer. The summary relative risk is about 1.3 (95 percent confidence intervals 1.2–1.5) and these data have been interpreted as supporting a causal role. In this review article, we discuss the chemical and morphological features of talc and asbestos, and explain why despite their similar chemical classification talc does not possess asbestos like carcinogenic properties. The heterogeneity in the perineal dusting studies has raised important concerns over the validity of the exposure measurements, and the lack of a consistent dose-response effect limits making causal inferences. Perhaps more importantly, whereas it is unknown whether external talc dust enters the female reproductive tract, measures of internal talc exposure such as talc-dusted diaphragms and latex condoms show no relationship with ovarian cancer risk. In addition, the therapeutic use of high dose cosmetic grade talc for pleurodesis has not been shown to cause cancer in patients receiving these treatment modalities. Talc is not genotoxic. Mechanistic, pathology and animal model studies have not found evidence for a carcinogenic effect. In summary, these data collectively do not indicate that cosmetic talc causes ovarian cancer. PMID:18287871

  5. Inhibiting DNA methylation activates cancer testis antigens and expression of the antigen processing and presentation machinery in colon and ovarian cancer cells.

    Science.gov (United States)

    Siebenkäs, Cornelia; Chiappinelli, Katherine B; Guzzetta, Angela A; Sharma, Anup; Jeschke, Jana; Vatapalli, Rajita; Baylin, Stephen B; Ahuja, Nita

    2017-01-01

    Innovative therapies for solid tumors are urgently needed. Recently, therapies that harness the host immune system to fight cancer cells have successfully treated a subset of patients with solid tumors. These responses have been strong and durable but observed in subsets of patients. Work from our group and others has shown that epigenetic therapy, specifically inhibiting the silencing DNA methylation mark, activates immune signaling in tumor cells and can sensitize to immune therapy in murine models. Here we show that colon and ovarian cancer cell lines exhibit lower expression of transcripts involved in antigen processing and presentation to immune cells compared to normal tissues. In addition, treatment with clinically relevant low doses of DNMT inhibitors (that remove DNA methylation) increases expression of both antigen processing and presentation and Cancer Testis Antigens in these cell lines. We confirm that treatment with DNMT inhibitors upregulates expression of the antigen processing and presentation molecules B2M, CALR, CD58, PSMB8, PSMB9 at the RNA and protein level in a wider range of colon and ovarian cancer cell lines and treatment time points than had been described previously. In addition, we show that DNMTi treatment upregulates many Cancer Testis Antigens common to both colon and ovarian cancer. This increase of both antigens and antigen presentation by epigenetic therapy may be one mechanism to sensitize patients to immune therapies.

  6. 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.

  7. Sustained, low-dose intraperitoneal cisplatin improves treatment outcome in ovarian cancer mouse models.

    Science.gov (United States)

    Ye, Hongye; Tanenbaum, Laura M; Na, Young Jeong; Mantzavinou, Aikaterini; Fulci, Giulia; del Carmen, Marcela G; Birrer, Michael J; Cima, Michael J

    2015-12-28

    Intraperitoneal (IP) chemotherapy for ovarian cancer treatment prolongs overall survival by 16 months compared to intravenous chemotherapy but is not widely practiced due to catheter-related complications and complexity of administration. An implantable, nonresorbable IP microdevice was used to release chemotherapeutic agent at a constant rate of approximately 1.3 μg/h in vitro and 1.0 μg/h in vivo. Studies conducted in two orthotopic murine models bearing human xenografts (SKOV3 and UCI101) demonstrate that continuous dosing reduces tumor burden to the same extent as weekly IP bolus drug injections. Treatment-induced toxicity was quantified via body weight loss and complete blood count. The microdevice resulted in significantly less toxicity than IP bolus injections, despite administration of higher cumulative doses (total area under the concentration-time curve of 3049 ng day/mL with the microdevice vs. 2118 ng-day/mL with IP bolus injections). This preclinical study supports the concept that reduced toxicity with similar efficacy outcomes can be achieved by continuous dosing in ovarian cancer patients currently treated with IP therapy.

  8. Histotype-specific copy-number alterations in ovarian cancer

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    Huang Ruby YunJu

    2012-10-01

    Full Text Available Abstract Background Epithelial ovarian cancer is characterized by multiple genomic alterations; most are passenger alterations which do not confer tumor growth. Like many cancers, it is a heterogeneous disease and can be broadly categorized into 4 main histotypes of clear cell, endometrioid, mucinous, and serous. To date, histotype-specific copy number alterations have been difficult to elucidate. The difficulty lies in having sufficient sample size in each histotype for statistical analyses. Methods To dissect the heterogeneity of ovarian cancer and identify histotype-specific alterations, we used an in silico hypothesis-driven approach on multiple datasets of epithelial ovarian cancer. Results In concordance with previous studies on global copy number alterations landscape, the study showed similar alterations. However, when the landscape was de-convoluted into histotypes, distinct alterations were observed. We report here significant histotype-specific copy number alterations in ovarian cancer and showed that there is genomic diversity amongst the histotypes. 76 cancer genes were found to be significantly altered with several as potential copy number drivers, including ERBB2 in mucinous, and TPM3 in endometrioid histotypes. ERBB2 was found to have preferential alterations, where it was amplified in mucinous (28.6% but deleted in serous tumors (15.1%. Validation of ERBB2 expression showed significant correlation with microarray data (p=0.007. There also appeared to be reciprocal relationship between KRAS mutation and copy number alterations. In mucinous tumors where KRAS mutation is common, the gene was not significantly altered. However, KRAS was significantly amplified in serous tumors where mutations are rare in high grade tumors. Conclusions The study demonstrates that the copy number landscape is specific to the histotypes and identification of these alterations can pave the way for targeted drug therapy specific to the histotypes.

  9. 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.

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

    Science.gov (United States)

    Dickinson, Rachel E; Fegan, K Scott; Ren, Xia; Hillier, Stephen G; Duncan, W Colin

    2011-01-01

    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 (PROBOs in normal OSE and PEO-14 cells (PROBO activity reduced apoptosis in both PEO-14 and SKOV-3 tumour cells (PROBO expression could be increased by reducing the expression of the glucocorticoid receptor using siRNA (PROBO 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.

  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. NUCKS nuclear elevated expression indicates progression and prognosis of ovarian cancer.

    Science.gov (United States)

    Shi, Ce; Qin, Ling; Gao, Hongyu; Gu, Lina; Yang, Chang; Liu, Hebing; Liu, Tianbo

    2017-09-01

    NUCKS (nuclear, casein kinase, and cyclin-dependent kinase substrate) is implicated in the tumorigenesis of several human malignancies, but its role in ovarian cancer remains unknown. We aim to investigate NUCKS expression and its clinical significance in ovarian cancer. The messenger RNA expression of NUCKS was determined in normal and malignant ovarian tissues using quantitative polymerase chain reaction assay. Immunohistochemistry was applied to detect the status of NUCKS protein expression in 121 ovarian cancer tissues. NUCKS protein high expression was detected in 52 (43.0%) of 121 patients. NUCKS messenger RNA expression was gradually upregulated in non-metastatic ovarian cancers ( n = 20), metastatic ovarian cancers ( n = 20), and its matched metastatic lesions ( n = 20) in comparison with that in normal ovarian tissues ( n = 10; p < 0.05). Elevated expression of NUCKS in ovarian cancer was associated significantly with the Federation of Gynecology and Obstetrics stage ( p = 0.037), histological grade ( p = 0.003), residual disease ( p = 0.013), lymph node metastasis ( p = 0.002), response to chemotherapy ( p < 0.001), and recurrence ( p = 0.013). In the multivariate Cox analysis, NUCKS expression was an independent prognostic marker for overall survival and disease-free survival in ovarian cancer with p values of <0.001 for both. Especially, NUCKS overexpression had prognostic potential for overall survival and disease-free survival ( p < 0.001 for both) in advanced ovarian cancers and only for disease-free survival in early ovarian cancers ( p = 0.017). Our data suggest that NUCKS overexpression may contribute to progression and poor prognosis in ovarian cancer especially in advanced ovarian cancer.

  13. Hydrogel Based 3-Dimensional (3D System for Toxicity and High-Throughput (HTP Analysis for Cultured Murine Ovarian Follicles.

    Directory of Open Access Journals (Sweden)

    Hong Zhou

    Full Text Available Various toxicants, drugs and their metabolites carry potential ovarian toxicity. Ovarian follicles, the functional unit of the ovary, are susceptible to this type of damage at all stages of their development. However, despite of the large scale of potential negative impacts, assays that study ovarian toxicity are limited. Exposure of cultured ovarian follicles to toxicants of interest served as an important tool for evaluation of toxic effects for decades. Mouse follicles cultured on the bottom of a culture dish continue to serve an important approach for mechanistic studies. In this paper, we demonstrated the usefulness of a hydrogel based 3-dimensional (3D mouse ovarian follicle culture as a tool to study ovarian toxicity in a different setup. The 3D in vitro culture, based on fibrin alginate interpenetrating network (FA-IPN, preserves the architecture of the ovarian follicle and physiological structure-function relationship. We applied the novel 3D high-throughput (HTP in vitro ovarian follicle culture system to study the ovotoxic effects of an anti-cancer drug, Doxorobucin (DXR. The fibrin component in the system is degraded by plasmin and appears as a clear circle around the encapsulated follicle. The degradation area of the follicle is strongly correlated with follicle survival and growth. To analyze fibrin degradation in a high throughput manner, we created a custom MATLAB® code that converts brightfield micrographs of follicles encapsulated in FA-IPN to binary images, followed by image analysis. We did not observe any significant difference between manually processed images to the automated MATLAB® method, thereby confirming that the automated program is suitable to measure fibrin degradation to evaluate follicle health. The cultured follicles were treated with DXR at concentrations ranging from 0.005 nM to 200 nM, corresponding to the therapeutic plasma levels of DXR in patients. Follicles treated with DXR demonstrated decreased

  14. Hydrogel Based 3-Dimensional (3D) System for Toxicity and High-Throughput (HTP) Analysis for Cultured Murine Ovarian Follicles.

    Science.gov (United States)

    Zhou, Hong; Malik, Malika Amattullah; Arab, Aarthi; Hill, Matthew Thomas; Shikanov, Ariella

    2015-01-01

    Various toxicants, drugs and their metabolites carry potential ovarian toxicity. Ovarian follicles, the functional unit of the ovary, are susceptible to this type of damage at all stages of their development. However, despite of the large scale of potential negative impacts, assays that study ovarian toxicity are limited. Exposure of cultured ovarian follicles to toxicants of interest served as an important tool for evaluation of toxic effects for decades. Mouse follicles cultured on the bottom of a culture dish continue to serve an important approach for mechanistic studies. In this paper, we demonstrated the usefulness of a hydrogel based 3-dimensional (3D) mouse ovarian follicle culture as a tool to study ovarian toxicity in a different setup. The 3D in vitro culture, based on fibrin alginate interpenetrating network (FA-IPN), preserves the architecture of the ovarian follicle and physiological structure-function relationship. We applied the novel 3D high-throughput (HTP) in vitro ovarian follicle culture system to study the ovotoxic effects of an anti-cancer drug, Doxorobucin (DXR). The fibrin component in the system is degraded by plasmin and appears as a clear circle around the encapsulated follicle. The degradation area of the follicle is strongly correlated with follicle survival and growth. To analyze fibrin degradation in a high throughput manner, we created a custom MATLAB® code that converts brightfield micrographs of follicles encapsulated in FA-IPN to binary images, followed by image analysis. We did not observe any significant difference between manually processed images to the automated MATLAB® method, thereby confirming that the automated program is suitable to measure fibrin degradation to evaluate follicle health. The cultured follicles were treated with DXR at concentrations ranging from 0.005 nM to 200 nM, corresponding to the therapeutic plasma levels of DXR in patients. Follicles treated with DXR demonstrated decreased survival rate in

  15. Psychological distress related to BRCA testing in ovarian cancer patients.

    Science.gov (United States)

    Bjørnslett, Merete; Dahl, Alv A; Sørebø, Øystein; Dørum, Anne

    2015-12-01

    An increasing demand for genetic testing has moved the procedure from highly selected at-risk individuals, now also including cancer patients for treatment associated testing. The heritable fraction of ovarian cancer is more than 10%, and our department has offered BRCA testing to such patients irrespective of family history since 2002. This study examined potential psychosocial distress associated with this procedure using The Multidimensional Impact of Cancer Risk Assessment (MICRA) questionnaire and other patient-rated generic distress instruments. Patients were divided into four groups according to cancer risk: mutation carriers, own history of breast cancer and ovarian cancer, family history of breast cancer and/or ovarian cancer, and patients without family history. In a postal survey, 354 patients responded. Good acceptance of the MICRA was observed, and previously described good psychometric properties were confirmed. A significant association between MICRA total score and receiving a positive BRCA test result was found. No significant between-group differences were observed with generic distress instruments. Time since cancer diagnosis, test result, and survey showed no significant associations with MICRA scores. Internal consistencies of instruments were adequate. Exploratory and confirmatory factor analyses showed adequate fit indices for a three factor solution of the MICRA, but further refinement of the items should be considered. In conclusion, the specific types of worry and distress most relevant to receiving genetic testing irrespective of family history were not captured by the generic distress instruments. The MICRA was supported as a useful tool for detection of mental distress related to genetic testing and risk evaluation.

  16. Serum tumor marker CA 125 for monitoring ovarian cancer during follow-up

    DEFF Research Database (Denmark)

    Tuxen, Malgorzata K.; Sölétormos, G; Dombernowsky, P

    2002-01-01

    CA 125 is currently widely applied in the management of patients with ovarian cancer. However, a change in results of CA 125, which should be considered significant, has not been defined. The aim of this study was to investigate the ability of CA 125 to signal progressive ovarian cancer during fo...... utility of serological tumor markers in patients with ovarian cancer.......CA 125 is currently widely applied in the management of patients with ovarian cancer. However, a change in results of CA 125, which should be considered significant, has not been defined. The aim of this study was to investigate the ability of CA 125 to signal progressive ovarian cancer during...... follow-up after first-line chemotherapy. The study patients were selected retrospectively among 255 patients with stage IC-IV ovarian cancer. The evaluation of the CA 125 information was based on the analytical imprecision, the normal intra-individual biological variation, the sampling interval...

  17. The Role of Endocrine G Protein-Coupled Receptors in Ovarian Cancer Progression.

    Science.gov (United States)

    Zhang, Qingyu; Madden, Nadine Ellen; Wong, Alice Sze Tsai; Chow, Billy Kwok Chong; Lee, Leo Tsz On

    2017-01-01

    Ovarian cancer is the seventh most common cancer in women and the most lethal gynecological cancer, causing over 151,000 deaths worldwide each year. Dysregulated production of endocrine hormones, known to have pluripotent effects on cell function through the activation of receptor signaling pathways, is believed to be a high-risk factor for ovarian cancer. An increasing body of evidence suggests that endocrine G protein-coupled receptors (GPCRs) are involved in the progression and metastasis of ovarian neoplasms. GPCRs are attractive drug targets because their activities are regulated by more than 25% of all drugs approved by the Food and Drug Administration. Therefore, understanding the role of endocrine GPCRs during ovarian cancer progression and metastasis will allow for the development of novel strategies to design effective chemotherapeutic drugs against malignant ovarian tumors. In this review, we address the signaling pathways and functional roles of several key endocrine GPCRs that are related to the cause, progression, and metastasis of ovarian cancer.

  18. A splicing variant of TERT identified by GWAS interacts with menopausal estrogen therapy in risk of ovarian cancer

    DEFF Research Database (Denmark)

    Lee, Alice W; Bomkamp, Ashley; Bandera, Elisa V

    2016-01-01

    Menopausal estrogen-alone therapy (ET) is a well-established risk factor for serous and endometrioid ovarian cancer. Genetics also plays a role in ovarian cancer, which is partly attributable to 18 confirmed ovarian cancer susceptibility loci identified by genome-wide association studies. The int......Menopausal estrogen-alone therapy (ET) is a well-established risk factor for serous and endometrioid ovarian cancer. Genetics also plays a role in ovarian cancer, which is partly attributable to 18 confirmed ovarian cancer susceptibility loci identified by genome-wide association studies...

  19. Early detection of ovarian cancer: preliminary results of the Yale Early Detection Program.

    OpenAIRE

    Schwartz, P. E.; Chambers, J. T.; Taylor, K. J.; Pellerito, J.; Hammers, L.; Cole, L. A.; Yang-Feng, T L; Smith, P; Mayne, S T; Makuch, R.

    1991-01-01

    Eighty-four women at high risk for ovarian cancer by having first-degree relatives with epithelial ovarian cancer participated in a newly established, early ovarian cancer detection program at Yale University. Participants were to be evaluated with physical examinations and circulating tumor markers at entry and every six months thereafter. Endovaginal ultrasound and color Doppler flow studies were to be performed at three and nine months following entry into the program. In addition, women w...

  20. ASSOCIATION BETWEEN OVARIAN CANCER RISK AND CONTRACEPTIVE METHODS- AN OBSERVATIONAL STUDY

    Directory of Open Access Journals (Sweden)

    Bessy Binu Sam

    2017-03-01

    Full Text Available BACKGROUND Ovarian cancer is the most lethal malignancy of the female reproductive system. Risk of ovarian cancer increases with age, but the rate of increase slows after the menopause. Use of contraceptives confers long-term protection against ovarian cancer. This observational study examines the correlation between ovarian cancer risks with different contraceptive methods. MATERIALS AND METHODS This study was conducted at Department of Obstetrics and Gynaecology, Government Medical College, Kottayam, Kerala, for a period of one year. Information was collected from 112 women diagnosed with ovarian cancer as treatment group and 336 women without ovarian cancer as control group. The Chi-square test was done to find the association of ovarian cancer risk with different contraceptive methods. RESULTS In the sample of 112 women with ovarian cancer, 53.6% women were using any of the contraceptive methods, whereas in the control group, only 5.1% women were using contraceptive methods. Our study found out a significant association of ovarian cancer risk with oral contraceptives and tubal ligation. There was no significant association of ovarian cancer risk with IUCD, sheath and vasectomy. CONCLUSION Tubal ligation and oral contraceptives reduce the risk of ovarian cancer. The dual benefits of tubal ligation need to be made aware among the public and tubal sterilisation rates have to be enhanced. Oral contraceptive pill use has to be propagated as a temporary contraceptive method due to its added advantage. We recommend future research on the association of ovarian cancer risk and contraceptive methods using large samples comparable to those done in developed countries.

  1. Clinical Trials with Pegylated Liposomal Doxorubicin in the Treatment of Ovarian Cancer

    OpenAIRE

    Carmela Pisano; Sabrina Chiara Cecere; Marilena Di Napoli; Carla Cavaliere; Rosa Tambaro; Gaetano Facchini; Cono Scaffa; Simona Losito; Antonio Pizzolorusso; Sandro Pignata

    2013-01-01

    Among the pharmaceutical options available for treatment of ovarian cancer, increasing attention has been progressively focused on pegylated liposomal doxorubicin (PLD), whose unique formulation prolongs the persistence of the drug in the circulation and potentiates intratumor accumulation. Pegylated liposomal doxorubicin (PLD) has become a major component in the routine management of epithelial ovarian cancer. In 1999 it was first approved for platinum-refractory ovarian cancer and then rece...

  2. Preclinical and Clinical Investigation of the Impact of Obesity on Ovarian Cancer Pathogenesis

    Science.gov (United States)

    2014-10-01

    Award Number: W81XWH-12-1-0426 TITLE: Preclinical and Clinical Investigation of the Impact of Obesity on Ovarian Cancer Pathogenesis PRINCIPAL...ANNUAL 25 Sep 2013 - 24 Sep 2014 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Pre-clinical and Clinical Investigation of the Impact of Obesity on Ovarian...metabolic consequences of obesity may be critical in the development of ovarian cancer (OC), resulting in biologically different cancers than those that

  3. Low Mutation Burden in Ovarian Cancer May Limit the Utility of Neoantigen-Targeted Vaccines.

    Directory of Open Access Journals (Sweden)

    Spencer D Martin

    Full Text Available Due to advances in sequencing technology, somatically mutated cancer antigens, or neoantigens, are now readily identifiable and have become compelling targets for immunotherapy. In particular, neoantigen-targeted vaccines have shown promise in several pre-clinical and clinical studies. However, to date, neoantigen-targeted vaccine studies have involved tumors with exceptionally high mutation burdens. It remains unclear whether neoantigen-targeted vaccines will be broadly applicable to cancers with intermediate to low mutation burdens, such as ovarian cancer. To address this, we assessed whether a derivative of the murine ovarian tumor model ID8 could be targeted with neoantigen vaccines. We performed whole exome and transcriptome sequencing on ID8-G7 cells. We identified 92 somatic mutations, 39 of which were transcribed, missense mutations. For the 17 top predicted MHC class I binding mutations, we immunized mice subcutaneously with synthetic long peptide vaccines encoding the relevant mutation. Seven of 17 vaccines induced robust mutation-specific CD4 and/or CD8 T cell responses. However, none of the vaccines prolonged survival of tumor-bearing mice in either the prophylactic or therapeutic setting. Moreover, none of the neoantigen-specific T cell lines recognized ID8-G7 tumor cells in vitro, indicating that the corresponding mutations did not give rise to bonafide MHC-presented epitopes. Additionally, bioinformatic analysis of The Cancer Genome Atlas data revealed that only 12% (26/220 of HGSC cases had a ≥90% likelihood of harboring at least one authentic, naturally processed and presented neoantigen versus 51% (80/158 of lung cancers. Our findings highlight the limitations of applying neoantigen-targeted vaccines to tumor types with intermediate/low mutation burdens.

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

    Science.gov (United States)

    Ovarian cancer, the deadliest of gynecologic cancers, is usually diagnosed at advanced stage due to invalidated screening test and non-specific symptoms presented. Although carboplatin has been popular for treating ovarian cancer for decades, patients eventually develop resistance to this platinum-c...

  5. 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

  6. 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

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

    NARCIS (Netherlands)

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

    2008-01-01

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

  8. 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

  9. Deciphering the Molecular Nature of Ovarian Cancer Biomarker CA125

    Directory of Open Access Journals (Sweden)

    Peter Hoffmann

    2012-08-01

    Full Text Available The ovarian cancer biomarker CA125 has been extensively investigated over the last 30 years. The knowledge about the exact molecular nature of this protein, however, remains fragmented. This review provides an overview of the structural research regarding CA125, and presents an orthogonal verification method to confirm the identity of this molecule. The need for independent identification of CA125 is exemplified by several reports where mutually exclusive data concerning the existence of isoforms and the glycan moieties is presented. Mass spectrometry can overcome the pitfalls of a single detection/identification method such as antibody probing. Independent verification of CA125 identity in characterization studies will help establish a refined model of its molecular structure that will promote the development of new approaches for diagnosis, prognosis and therapy of ovarian cancer.

  10. 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.

  11. Epidemiology and etiology of ovarian cancer: a review

    Energy Technology Data Exchange (ETDEWEB)

    Heintz, A.P.; Hacker, N.F.; Lagasse, L.D.

    1985-07-01

    Ovarian cancer is the most frequent cause of death from gynecologic malignancies in the western world. Much effort has been put into attempts to correlate differences in incidence rates with environmental, endocrinologic, and genetic factors. A review of the literature reveals that there is currently no evidence to incriminate any single etiologic factor for this group of tumors. There is growing evidence of familial predisposition in a small group of patients and of a relationship with reproductive history. If current knowledge of the epidemiology of ovarian cancer is to be translated into disease prevention, more attention should be paid to women at risk because of their family history, and more awareness should be made of the protective effect of oral contraceptives. 79 references.

  12. Chronic recreational physical inactivity and epithelial ovarian cancer risk

    DEFF Research Database (Denmark)

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

    2016-01-01

    . We conducted a pooled analysis of nine studies from the Ovarian Cancer Association Consortium to investigate the association between chronic recreational physical inactivity and EOC risk. Methods: In accordance with the 2008 Physical Activity Guidelines for Americans, women reporting no regular......Background: Despite a large body of literature evaluating the association between recreational physical activity and epithelial ovarian cancer (EOC) risk, the extant evidence is inconclusive, and little is known about the independent association between recreational physical inactivity and EOC risk......, weekly recreational physical activity were classified as inactive. Multivariable logistic regression was utilized to estimate the ORs and 95% confidence intervals (CI) for the association between inactivity and EOC risk overall and by subgroups based upon histotype, menopausal status, race, and body mass...

  13. [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.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  15. 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

  16. Laparoscopic ovarian transposition before pelvic radiation in rectal cancer patient: safety and feasibility

    Directory of Open Access Journals (Sweden)

    Al-Asari Sami

    2012-09-01

    Full Text Available Abstract Background Infertility due to pelvic radiation for advanced rectal cancer treatment is a major concern particularly in young patients. Pre-radiation laparoscopic ovarian transposition may offer preservation of ovarian function during the treatment however its use is limited. Aim The study investigates the safety, feasibility and effectiveness of pre-radiation laparoscopic ovarian transposition and its effect on ovarian function in the treatment o locally advanced rectal cancer. Methods Charts review of all young female patients diagnosed with locally advanced rectal cancer, underwent laparoscopic ovarian transposition, then received preoperative radiotherapy at king Faisal Specialist Hospital and Research Centre between 2003–2007. Results During the period studied three single patients age between 21–27 years underwent pre-radiation laparoscopic ovarian transposition for advanced rectal cancer. All required pretreatment laparoscopic diversion stoma due to rectal stricture secondary to tumor that was performed at the same time. One patient died of metastatic disease during treatment. The ovarian hormonal levels (FSH and LH were normal in two patients. One has had normal menstrual period and other had amenorrhoea after 4 months follow-up however her ovarian hormonal level were within normal limits. Conclusions Laparoscopic ovarian transposition before pelvic radiation in advanced rectal cancer treatment is an effective and feasible way of preservation of ovarian function in young patients at risk of radiotherapy induced ovarian failure. However, this procedure is still under used and it is advisable to discuss and propose it to suitable patients.

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

    DEFF Research Database (Denmark)

    Dafou, Dimitra; Grun, Barbara; Sinclair, John

    2010-01-01

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

  18. Early detection of ovarian cancer: background, rationale, and structure of the Yale Early Detection Program.

    Science.gov (United States)

    Schwartz, P. E.; Chambers, J. T.; Taylor, K. J.; Pellerito, J.; Hammers, L.; Cole, L. A.; Yang-Feng, T. L.; Smith, P.; Mayne, S. T.; Makuch, R.

    1991-01-01

    Ovarian cancer has received national attention as a highly virulent disease. Its lack of early warning symptoms and the failure to develop highly sensitive screening tests have led some physicians to recommend prophylactic oophorectomies to women with relatives who have had ovarian cancer. Others have recommended routine screening of otherwise normal women for CA 125, a circulating tumor marker, and ultrasound examinations. Each of these techniques is associated with substantial false-positive rates that could lead to unnecessary surgery. A review of epidemiologic data suggests that familial ovarian cancer kindreds are rare, but women with first-degree relatives who have had ovarian cancer have a significant risk themselves for developing ovarian cancer. In addition, women with a great number of ovulatory cycles are at an increased risk for the disease. Circulating tumor markers are frequently elevated in women with advanced ovarian cancer, but their value in early detection of ovarian cancer has yet to be established. Advances in endovaginal ultrasound and color Doppler flow technology have significantly improved our ability to assess pelvic organs. This article presents the background, rationale, and structure of the Yale Early Detection Program for ovarian cancer, whose goals are to identify the best techniques for diagnosing ovarian cancer in an early stage, to determine the frequency with which such tests should be employed, to assess false-positive results, and to identify women who might benefit from prophylactic oophorectomies. PMID:1810100

  19. Investigation of ovarian cancer associated sialylation changes in N-linked glycopeptides by quantitative proteomics

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    Shetty Vivekananda

    2012-08-01

    Full Text Available Abstract Background In approximately 80% of patients, ovarian cancer is diagnosed when the patient is already in the advanced stages of the disease. CA125 is currently used as the marker for ovarian cancer; however, it lacks specificity and sensitivity for detecting early stage disease. There is a critical unmet need for sensitive and specific routine screening tests for early diagnosis that can reduce ovarian cancer lethality by reliably detecting the disease at its earliest and treatable stages. Results In this study, we investigated the N-linked sialylated glycopeptides in serum samples from healthy and ovarian cancer patients using Lectin-directed Tandem Labeling (LTL and iTRAQ quantitative proteomics methods. We identified 45 N-linked sialylated glycopeptides containing 46 glycosylation sites. Among those, ten sialylated glycopeptides were significantly up-regulated in ovarian cancer patients’ serum samples. LC-MS/MS analysis of the non-glycosylated peptides from the same samples, western blot data using lectin enriched glycoproteins of various ovarian cancer type samples, and PNGase F (+/− treatment confirmed the sialylation changes in the ovarian cancer samples. Conclusion Herein, we demonstrated that several proteins are aberrantly sialylated in N-linked glycopeptides in ovarian cancer and detection of glycopeptides with abnormal sialylation changes may have the potential to serve as biomarkers for ovarian cancer.

  20. miR-214 promotes radioresistance in human ovarian cancer cells by targeting PETN.

    Science.gov (United States)

    Zhang, Qin; Zhang, Shuxiang

    2017-08-31

    Ovarian cancer is one of the leading causes of death among gynecological malignancies. Increasing evidence indicate that dysregulation of microRNAs (miRNAs) plays an important role in tumor radioresistance. The aim of the present study is to investigate whether microRNA-214 (miR-214) was involved in radioresistance of human ovarian cancer. Here, we showed that miR-214 was significantly up-regulated in ovarian cancer tissues and radioresistance ovarian cancer cell lines. Transfection of miR-214 agomir in radiosensitive ovarian cancer cell lines promoted them for resistance to ionizing radiation, whereas transfection of miR-214 antagomir in radioresistance ovarian cancer cell lines sensitized them to ionizing radiation again. Furthermore, we found miR-214 effectively promoted tumor radioresistance in xenograft animal experiment. Western blotting and quantitative real-time PCR demonstrated that miR-214 negatively regulated PTEN in radioresistance ovarian cancer cell lines and ovarian cancer tissues. Taken together, our data conclude that miR-214 contributes to radioresistance of ovarian cancer by directly targeting PTEN. © 2017 The Author(s).

  1. Optimizing Molecular-Targeted Therapies in Ovarian Cancer: The Renewed Surge of Interest in Ovarian Cancer Biomarkers and Cell Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Donavon Hiss

    2012-01-01

    Full Text Available The hallmarks of ovarian cancer encompass the development of resistance, disease recurrence and poor prognosis. Ovarian cancer cells express gene signatures which pose significant challenges for cancer drug development, therapeutics, prevention and management. Despite enhancements in contemporary tumor debulking surgery, tentative combination regimens and abdominal radiation which can achieve beneficial response rates, the majority of ovarian cancer patients not only experience adverse effects, but also eventually relapse. Therefore, additional therapeutic possibilities need to be explored to minimize adverse events and prolong progression-free and overall response rates in ovarian cancer patients. Currently, a revival in cancer drug discovery is devoted to identifying diagnostic and prognostic ovarian cancer biomarkers. However, the sensitivity and reliability of such biomarkers may be complicated by mutations in the BRCA1 or BRCA2 genes, diverse genetic risk factors, unidentified initiation and progression elements, molecular tumor heterogeneity and disease staging. There is thus a dire need to expand existing ovarian cancer therapies with broad-spectrum and individualized molecular targeted approaches. The aim of this review is to profile recent developments in our understanding of the interrelationships among selected ovarian tumor biomarkers, heterogeneous expression signatures and related molecular signal transduction pathways, and their translation into more efficacious targeted treatment rationales.

  2. 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...

  3. Biological Basis for Chemoprevention of Ovarian Cancer. Addendum

    Science.gov (United States)

    2007-10-01

    in first-degree and second-degree relatives, menstrual characteristics, preg- nancy and breast-feeding history, infertility , hormone use, and...Quartile 4: >0.876 NA NA 36 (37) 34 (24) Infertility , doctor diagnosed in female Yes 62 (13) 53 (10) 0.166 8 (8) 10 (7) 0.775 No 433 (87) 487 (90) 91 (92...epidemiologic studies that have examined the relationship between reproductive history, hormone use and ovarian cancer. It has been convincingly

  4. Pro-lipogenic Action of Lysophosphatidic Acid in Ovarian Cancer

    Science.gov (United States)

    2014-04-01

    their nonselective suppression of fatty acid synthesis in both normal andmalignant tissues, which could deteriorate weight loss , anorexia, fatigue, and... supplemented LPA did not fully reverse the effect of the iPLA2β inhibitor BEL on cell cycling (8), suggesting involvement of additional bioactive...dominant-negative form was found to inhibit growth of ovarian cancer cell lines (Fig. 5). Furthermore, inhibition of carnitine palmitoyl transferase 1A

  5. Pegylated liposomal doxorubicin in the management of ovarian cancer

    OpenAIRE

    Ferrandina, Gabriella

    2010-01-01

    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 progressi...

  6. Development of a Multifaceted Ovarian Cancer Imaging Agent

    Science.gov (United States)

    2010-04-01

    method for a recombinant disintegrin vicrostatin (VN), whose structure is based on the snake venom disintegrin contortrostatin (CN), and the use of the...TITLE: Development of a Multifaceted Ovarian Cancer Imaging Agent PRINCIPAL INVESTIGATOR: Francis S . Markland Ph.D...distribution unlimited The views, opinions and/or findings contained in this report are those of the author( s ) and should not be construed

  7. Junk DNA-Encoded Antigens in Ovarian Cancer

    Science.gov (United States)

    2014-10-01

    SUBTITLE Junk DNA-Encoded Antigens in Ovarian Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-13-1-0359 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR...ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBER The Johns Hopkins University School of Medicine 733 North Broadway, Suite 117 ...recombinase inactivates homozygous floxed alleles of p53 and Rb1. We also increased our understanding of aberrant ORF1p long interspersed element -1

  8. 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.

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

    Directory of Open Access Journals (Sweden)

    Vinod Vathipadiekal

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

  10. Exosomes mediated pentose phosphate pathway in ovarian cancer metastasis: a proteomics analysis.

    Science.gov (United States)

    Yi, Huan; Zheng, Xiangqin; Song, Jianrong; Shen, Rongkai; Su, Yanzhao; Lin, Danmei

    2015-01-01

    Epithelial ovarian cancer is the most lethal gynecological malignancies for readily metastasis. Exosomes have played an influential role in carcinogenicity and cancer progression. Our aim is to discover exosome-related mechanisms in ovarian cancer progress and explore potential diagnostic biomarkers and therapeutic targets of ovarian cancer. We initially presented the proteomic profiles of exosomes derived from two late-stage ovarian cell lines, OVCA429 and HO8910PM. A total of 2940 exosomal proteins were recorded by MS. FunRich appropriately processed these exosomal proteins, manifesting some superiority in contrast to Blast2go. Moreover, we demonstrated the pentose phosphate pathway was a dominant mechanism in exosome mediated intracellular communication. Glucose-6-phosphate dehydrogenase, transketolase and transaldolase 1, three key enzymes regulated pentose phosphate pathway, were all marked in the same exosomal parts of proteins between two ovarian cell lines. Moreover, these key proteins might become diagnostic, prognostic biomarkers and therapeutic targets of ovarian cancer.

  11. Adenovirus-based p53 gene therapy in ovarian cancer.

    Science.gov (United States)

    Santoso, J T; Tang, D C; Lane, S B; Hung, J; Reed, D J; Muller, C Y; Carbone, D P; Lucci, J A; Miller, D S; Mathis, J M

    1995-11-01

    Mutations of the p53 tumor suppressor gene are the most common molecular genetic abnormality to be described in ovarian cancer. To determine the feasibility of mutant p53 as a molecular target for gene therapy in ovarian cancer, we constructed an adenovirus vector containing the wild-type p53 gene. The ability of this adenovirus construct (Ad-CMV-p53) to express p53 protein was examined by Western blot analysis in the H358 lung cancer cell line, which has a homozygous deletion of the p53 gene. The ability of the adenovirus vector system to infect ovarian cancer cells was tested using an adenovirus containing the beta-galactosidase reporter gene under the control of the CMV promoter (Ad-CMV-beta gal). The ovarian cancer cell line 2774, which contains an Arg273His p53 mutation, was infected with Ad-CMV-beta gal, and the infected cells were assayed for beta-galactosidase activity after 24 hr. To test the ability of wild-type p53 to inhibit cell growth, the 2774 cell line was infected with Ad-CMV-p53 or Ad-CMV-beta gal, and the effect of these agents on the growth of 2774 cells was determined using an in vitro growth inhibition assay. Western blot analysis of lysates from H358 cells infected with Ad-CMV-p53 showed expression of wild-type p53 protein. When 2774 cells were infected with Ad-CMV-beta gal at a multiplicity of infection (m.o.i.) of 10 PFU/cell, > 90% of cells showed beta-galactosidase activity, demonstrating that these cells are capable of efficient infection by the adenovirus vector. Growth of 2774 cells infected with Ad-CMV-p53 was inhibited by > 90% compared to noninfected cells. The ability of the adenovirus vector to mediate high-level expression of infected genes and the inhibitory effect of Ad-CMV-p53 on the 2774 cell line suggests that the Ad-CMV-p53 could be further developed into a therapeutic agent for ovarian cancer.

  12. Mesothelial neoplasms presenting as, and mimicking, ovarian cancer.

    Science.gov (United States)

    Mani, Haresh; Merino, Maria J

    2010-11-01

    Mesotheliomas of the abdominal cavity are rare tumors that primarily involve the peritoneum, mesentery, and omentum. The involvement of the viscera is usually secondary to bulky and extensive serosal disease. We describe 7 cases of mesothelioma in which the initial manifestation was that of an ovarian mass. All patients underwent surgery with a primary diagnosis of ovarian cancer. Clinical histories, gross features, and histology slides were reviewed. Immunostains were performed on all cases and electron microscopy was performed in 2 cases. The patients ranged in age from 22 to 52 years and the lesions ranged in size from 3.8 to 9 cm. Of the 7 cases, 4 were predominantly cystic and 3 were solid. Histologically, all cystic tumors were multicystic mesothelioma, whereas the 3 solid tumors were diffuse malignant mesotheliomas. One patient had a borderline mucinous tumor with the mesothelioma occurring as a mural nodule, an association not described earlier. The oldest patient in this series had a diffuse malignant mesothelioma of the peritoneum with predominant ovarian surface involvement. Mesothelial neoplasms can present as ovarian masses in young women. Awareness of this presentation is important to establish appropriate management.

  13. 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.

  14. 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.

  15. Chlamydia Peritonitis and Ascites Mimicking Ovarian Cancer

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    Anar Gojayev

    2016-01-01

    Full Text Available Background. Pelvic inflammatory disease (PID rarely results in diffuse ascites. Severe adhesive disease secondary to PID may lead to the formation of inclusion cysts and even pelvic peritoneal nodularity due to postinflammatory scarring and cause an elevation of serum CA-125 levels. The constellation of these findings may mimic an ovarian neoplasm. Case. We report a case of a 22-year-old female who presented with multiple pelvic cysts and diffuse ascites due to Chlamydia trachomatis infection. The initial gynecologic exam did not reveal obvious evidence of PID; however, a positive Chlamydia trachomatis test, pathologic findings, and the exclusion of other etiologies facilitated the diagnosis. Conclusion. Chlamydia trachomatis and other infectious agents should be considered in the differential diagnosis of a young sexually active female with abdominal pain, ascites, and pelvic cystic masses. Thorough workup in such a population may reduce the number of more invasive procedures as well as unnecessary repeat surgical procedures.

  16. Chlamydia Peritonitis and Ascites Mimicking Ovarian Cancer

    Science.gov (United States)

    Macer, Matthew; Azodi, Masoud

    2016-01-01

    Background. Pelvic inflammatory disease (PID) rarely results in diffuse ascites. Severe adhesive disease secondary to PID may lead to the formation of inclusion cysts and even pelvic peritoneal nodularity due to postinflammatory scarring and cause an elevation of serum CA-125 levels. The constellation of these findings may mimic an ovarian neoplasm. Case. We report a case of a 22-year-old female who presented with multiple pelvic cysts and diffuse ascites due to Chlamydia trachomatis infection. The initial gynecologic exam did not reveal obvious evidence of PID; however, a positive Chlamydia trachomatis test, pathologic findings, and the exclusion of other etiologies facilitated the diagnosis. Conclusion. Chlamydia trachomatis and other infectious agents should be considered in the differential diagnosis of a young sexually active female with abdominal pain, ascites, and pelvic cystic masses. Thorough workup in such a population may reduce the number of more invasive procedures as well as unnecessary repeat surgical procedures. PMID:27747116

  17. Rad6 upregulation promotes stem cell-like characteristics and platinum resistance in ovarian cancer

    Science.gov (United States)

    Somasagara, Ranganatha R.; Tripathi, Kaushlendra; Spencer, Sebastian M.; Clark, David W.; Barnett, Reagan; Bachaboina, Lavanya; Scalici, Jennifer; Rocconi, Rodney P.; Piazza, Gary A.; Palle, Komaraiah

    2015-01-01

    Ovarian cancer is the fifth most deadly cancer in women in the United States and despite advances in surgical and chemotherapeutic treatments survival rates have not significantly improved in decades. The poor prognosis for ovarian cancer patients is largely due to the extremely high (80%) recurrence rate of ovarian cancer and because the recurrent tumors are often resistant to the widely utilized platinum-based chemotherapeutic drugs. In this study, expression of Rad6, an E2 ubiquitin-conjugating enzyme, was found to strongly correlate with ovarian cancer progression. Furthermore, in ovarian cancer cells Rad6 was found to stabilize β-catenin promoting stem cell-related characteristics, including expression of stem cell markers and anchorage-independent growth. Cancer stem cells can promote chemoresistance, tumor recurrence and metastasis, all of which are limiting factors in treating ovarian cancer. Thus it is significant that Rad6 overexpression led to increased resistance to the chemotherapeutic drug carboplatin and correlated with tumor cell invasion. These findings show the importance of Rad6 in ovarian cancer and emphasize the need for further studies of Rad6 as a potential target for the treatment of ovarian cancer. PMID:26679603

  18. 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

  19. 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.

  20. CLINICAL SIGNIFICANCE OF BIOMARKERS IN OVARIAN CANCER, PROSTATE CANCER, COLORECTAL CANCER

    Directory of Open Access Journals (Sweden)

    N. V. Marshutina

    2016-01-01

    Full Text Available The review is devoted to modern notions about serum tumor markers and their place in oncology: using for differential diagnosis, in prognosis of course of tumor process, during follow-up, for preclinical detection of disease recurrences, as well as in screening aimed at early detection of malignant neoplasms. Algorithms of using of most informative tumor markers: CA125, HE4 (in ovarian cancer, PSA and its isoforms (in prostate cancer, iFOBT (in colorectal cancer were described.

  1. Ovarian metastasis in colorectal cancer: retrospective review of 180 cases

    Directory of Open Access Journals (Sweden)

    Omranipour R

    2009-12-01

    Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Routine oophorectomy in women with colorectal cancer is under debate, the aim of this study is to determine incidence, clinicopathologic features and prognostic factors of ovarian involvement in primary colorectal cancer (CRC and to clear the role of prophylactic oophorectomy."n"nMethods: Data from primary CRC women treated between years 1990 and 2004 were retrieved and clinical and pathologic features of those who had undergone oophorectomy during CRC surgery were reviewed."n"nResults: One hundred eighty cases (mean age 47.5 years were included. In 120(66.6%, ovaries were preserved and 60(33.3% cases underwent bilateral oophorectomy in addition to primary CRC resection. Reasons for oophorectomy were prophylactic in 22(36.6%, abnormal morphology in 35(58.3%, and undetermined in 3(5% cases. There were five metastatic carcinomas, eight primary ovarian tumors and 47 normal ovaries in pathologic evaluation. No complication directly related to oophorectomy was noted. Patients with ovarian metastases had higher stages of tumor. Ovarian metastases were not related to menstrual status, CRC location, size, differentiation, and mucin production, as well as abnormal morphology of ovary. The global prevalence of

  2. 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.

  3. Notch pathway promotes ovarian cancer growth and migration via CXCR4/SDF1α chemokine system.

    Science.gov (United States)

    Chiaramonte, R; Colombo, M; Bulfamante, G; Falleni, M; Tosi, D; Garavelli, S; De Simone, D; Vigolo, E; Todoerti, K; Neri, A; Platonova, N

    2015-09-01

    Ovarian cancer is the most deadly gynecological malignancy. Understanding the molecular pathogenesis of ovarian cancer is critical to provide new targeted therapeutic strategies. Recent evidence supports a role for Notch in ovarian cancer progression and associates its dysregulation to poor overall survival. Similarly, CXCR4/SDF1α signalling correlates with ovarian cancer progression and metastasis. Recent findings indicate that Notch promotes CXCR4/SDF1α signalling and its effect on cell growth and migration; nonetheless, up to now, the association between Notch and CXCR4/SDFα in ovarian cancer has not been reported. Thereby, the aim of this study was to investigate if Notch and CXCR4/SDF1α cooperate in determining ovarian cancer growth, survival and migration. To address this issue, Notch signalling was inhibited by using γ-secretase inhibitors, or upregulated by forcing of Notch1 expression in ovarian cancer cell lines. Our results indicated that Notch activity influenced tumour cell growth and survival and positively regulated CXCR4 and SDF1α expression. CXCR4/SDF1α signalling mediated the effect of Notch pathway on ovarian cancer cell growth and SDF1α-driven migration. Additionally, for the first time, we demonstrated that Notch signalling activation can be detected in ovarian cancer specimens by immunohistochemistry analysis of the Notch transcriptional target, HES6 and is positively correlated with high expression levels of CXCR4 and SDF1α. Our results demonstrate that Notch affects ovarian cancer cell biology through the modulation of CXCR4/SDF1α signalling and suggest that Notch inhibition may be a rationale therapeutic approach to hamper ovarian cancer progression mediated by the CXCR4/SDF1α axis.

  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. 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.

    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

  6. Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial

    Science.gov (United States)

    Jacobs, Ian J; Menon, Usha; Ryan, Andy; Gentry-Maharaj, Aleksandra; Burnell, Matthew; Kalsi, Jatinderpal K; Amso, Nazar N; Apostolidou, Sophia; Benjamin, Elizabeth; Cruickshank, Derek; Crump, Danielle N; Davies, Susan K; Dawnay, Anne; Dobbs, Stephen; Fletcher, Gwendolen; Ford, Jeremy; Godfrey, Keith; Gunu, Richard; Habib, Mariam; Hallett, Rachel; Herod, Jonathan; Jenkins, Howard; Karpinskyj, Chloe; Leeson, Simon; Lewis, Sara J; Liston, William R; Lopes, Alberto; Mould, Tim; Murdoch, John; Oram, David; Rabideau, Dustin J; Reynolds, Karina; Scott, Ian; Seif, Mourad W; Sharma, Aarti; Singh, Naveena; Taylor, Julie; Warburton, Fiona; Widschwendter, Martin; Williamson, Karin; Woolas, Robert; Fallowfield, Lesley; McGuire, Alistair J; Campbell, Stuart; Parmar, Mahesh; Skates, Steven J

    2016-01-01

    Summary Background Ovarian cancer has a poor prognosis, with just 40% of patients surviving 5 years. We designed this trial to establish the effect of early detection by screening on ovarian cancer mortality. Methods In this randomised controlled trial, we recruited postmenopausal women aged 50–74 years from 13 centres in National Health Service Trusts in England, Wales, and Northern Ireland. Exclusion criteria were previous bilateral oophorectomy or ovarian malignancy, increased risk of familial ovarian cancer, and active non-ovarian malignancy. The trial management system confirmed eligibility and randomly allocated participants in blocks of 32 using computer-generated random numbers to annual multimodal screening (MMS) with serum CA125 interpreted with use of the risk of ovarian cancer algorithm, annual transvaginal ultrasound screening (USS), or no screening, in a 1:1:2 ratio. The primary outcome was death due to ovarian cancer by Dec 31, 2014, comparing MMS and USS separately with no screening, ascertained by an outcomes committee masked to randomisation group. All analyses were by modified intention to screen, excluding the small number of women we discovered after randomisation to have a bilateral oophorectomy, have ovarian cancer, or had exited the registry before recruitment. Investigators and participants were aware of screening type. This trial is registered with ClinicalTrials.gov, number NCT00058032. Findings Between June 1, 2001, and Oct 21, 2005, we randomly allocated 202 638 women: 50 640 (25·0%) to MMS, 50 639 (25·0%) to USS, and 101 359 (50·0%) to no screening. 202 546 (>99·9%) women were eligible for analysis: 50 624 (>99·9%) women in the MMS group, 50 623 (>99·9%) in the USS group, and 101 299 (>99·9%) in the no screening group. Screening ended on Dec 31, 2011, and included 345 570 MMS and 327 775 USS annual screening episodes. At a median follow-up of 11·1 years (IQR 10·0–12·0), we diagnosed ovarian cancer in

  7. Paclitaxel and Carboplatin or Ifosfamide in Treating Patients With Newly Diagnosed Persistent or Recurrent Uterine, Ovarian, Fallopian Tube, or Peritoneal Cavity Cancer

    Science.gov (United States)

    2014-12-23

    Ovarian Carcinosarcoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Recurrent Uterine Corpus Sarcoma; Stage I Ovarian Cancer; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Cancer; Stage IA Uterine Sarcoma; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Cancer; Stage IB Uterine Sarcoma; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Cancer; Stage IC Uterine Sarcoma; Stage II Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIA Uterine Sarcoma; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIB Uterine Sarcoma; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIA Uterine Sarcoma; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIB Uterine Sarcoma; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IIIC Uterine Sarcoma; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer; Stage IVA Uterine Sarcoma; Stage IVB Uterine Sarcoma; Uterine Carcinosarcoma

  8. 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...

  9. 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...

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

    Science.gov (United States)

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

    2017-03-22

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

  11. Multimodal nonlinear optical microscopy used to discriminate epithelial ovarian cancer

    Science.gov (United States)

    Adur, J.; Pelegati, V. B.; de Thomaz, A. A.; Almeida, D. B.; Bottcher-Luiz, F.; Andrade, L. A. L. A.; Cesar, C. L.

    2011-07-01

    We used human specimens of epithelial ovarian cancer (serous type) to test the feasibility of nonlinear imaging as complementary tools for ovarian cancer diagnosis. Classical hematoxylin-and-eosin stained sections were applied to combining two-photon excitation fluorescence (TPEF), second (SHG), and third (THG) harmonic microscopy within the same imaging platform. We show that strong TPEF + SHG + THG signals can be obtained in fixed samples stained with Hematoxylin & Eosin (H&E) stored for a very long time and that H&E staining enhanced the THG signal. We demonstrate using anisotropy and morphological measurements, that SHG and THG of stained optical sections allow reproducible identification of neoplastic features such as architectural alterations of collagen fibrils at different stages of the neoplastic transformation and cellular atypia. Taken together, these results suggest that, with our viable imaging system, we can qualitatively and quantitatively assess endogenous optical biomarkers of the ovarian tissue with SHG and THG microscopy. This imaging capability may prove to be highly valuable in aiding to determine structural changes at the cellular and tissue levels, which may contribute to the development of new diagnostic techniques.

  12. 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.

  13. Update on PARP1 inhibitors in ovarian cancer.

    Science.gov (United States)

    Sessa, C

    2011-12-01

    The clinical development of PARP inhibitors for the treatment of tumors deficient in BRCA1 or BRCA2 is based on the concept of synthetic lethality. From the initial proof of concept study with the PARP1 inhibitor olaparib (AZD2281) in BRCA mutation carriers, in which 28% of ovarian cancer patients achieved an objective response, the target population of ovarian patients potentially sensitive to treatment with PARP inhibitors has greatly increased. Objective responses have been observed in both platinum-sensitive and platinum-resistant BRCA mutation carriers but, more recently, also in BRCA negative 'BRCAness' patients, those with no BRCA mutations but with a dysfunction of the homologous recombination (HR) system, which makes them more sensitive to the antitumor agents which cause double strand breaks of DNA. The recent results achieved with olaparib, given as maintenance in platinum sensitive recurrent high grade serous ovarian cancer, in response after reinduction with platinum, confirm the antitumor effect of single agent olaparib in BRCAness patients. Main topics of investigations in this field are the identification of BRCAness phenotype and the definition of tests to identify BRCAness patients. More in general, additional preclinical studies are needed to further improve clinical results in order to define the optimal regimen of combination with PARP1 inhibitor and cytotoxics or molecular targeted agents (sequence of administration, interval between dosing of the agents, duration of treatment).

  14. 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.

  15. 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.

  16. 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.

  17. 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.

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

    Science.gov (United States)

    Xia, Yan; Zhang, Yin-Li; Yu, Chao; Chang, Ting; Fan, Heng-Yu

    2014-01-01

    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.

  19. BRCA 1/2-mutation related and sporadic breast and ovarian cancers: More alike than different

    Directory of Open Access Journals (Sweden)

    Melissa A. Burgess

    2014-02-01

    Full Text Available No longer is histology solely predictive of cancer treatment and outcome. There is an increasing influence of tumor genomic characteristics on therapeutic options. Both breast and ovarian cancers are at higher risk of development in patients with BRCA 1/2-germline mutations. Recent data from the Cancer Genome Atlas (TCGA and others have shown a number of genomic similarities between triple negative breast cancers and ovarian cancers. Recently, poly (ADP-ribose polymerase (PARP inhibitors have shown promising activity in hereditary BRCA 1/2-mutated and sporadic breast and ovarian cancers. In this review, we will summarize the current literature regarding the genomic and phenotypic similarities between BRCA 1/2-mutation related cancers, sporadic triple negative breast cancers, and sporadic ovarian cancers. We will also review phase I, II, and III data using PARP inhibitors for these malignancies and compare and contrast the results with respect to histology.

  20. Goserelin for ovarian protection during breast-cancer adjuvant chemotherapy.

    Science.gov (United States)

    Moore, Halle C F; Unger, Joseph M; Phillips, Kelly-Anne; Boyle, Frances; Hitre, Erika; Porter, David; Francis, Prudence A; Goldstein, Lori J; Gomez, Henry L; Vallejos, Carlos S; Partridge, Ann H; Dakhil, Shaker R; Garcia, Agustin A; Gralow, Julie; Lombard, Janine M; Forbes, John F; Martino, Silvana; Barlow, William E; Fabian, Carol J; Minasian, Lori; Meyskens, Frank L; Gelber, Richard D; Hortobagyi, Gabriel N; Albain, Kathy S

    2015-03-05

    Ovarian failure is a common toxic effect of chemotherapy. Studies of the use of gonadotropin-releasing hormone (GnRH) agonists to protect ovarian function have shown mixed results and lack data on pregnancy outcomes. We randomly assigned 257 premenopausal women with operable hormone-receptor-negative breast cancer to receive standard chemotherapy with the GnRH agonist goserelin (goserelin group) or standard chemotherapy without goserelin (chemotherapy-alone group). The primary study end point was the rate of ovarian failure at 2 years, with ovarian failure defined as the absence of menses in the preceding 6 months and levels of follicle-stimulating hormone (FSH) in the postmenopausal range. Rates were compared with the use of conditional logistic regression. Secondary end points included pregnancy outcomes and disease-free and overall survival. At baseline, 218 patients were eligible and could be evaluated. Among 135 with complete primary end-point data, the ovarian failure rate was 8% in the goserelin group and 22% in the chemotherapy-alone group (odds ratio, 0.30; 95% confidence interval [CI], 0.09 to 0.97; two-sided P=0.04). Owing to missing primary end-point data, sensitivity analyses were performed, and the results were consistent with the main findings. Missing data did not differ according to treatment group or according to the stratification factors of age and planned chemotherapy regimen. Among the 218 patients who could be evaluated, pregnancy occurred in more women in the goserelin group than in the chemotherapy-alone group (21% vs. 11%, P=0.03); women in the goserelin group also had improved disease-free survival (P=0.04) and overall survival (P=0.05). Although missing data weaken interpretation of the findings, administration of goserelin with chemotherapy appeared to protect against ovarian failure, reducing the risk of early menopause and improving prospects for fertility. (Funded by the National Cancer Institute and others; POEMS/S0230 Clinical

  1. 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.

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

    Directory of Open Access Journals (Sweden)

    Karina Biskup

    2014-01-01

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

  3. 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

  4. 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.

  5. Do We Know What Causes Ovarian Cancer?

    Science.gov (United States)

    ... Center Volunteer Learning Center Follow Us Twitter Facebook Instagram Cancer Information, Answers, and Hope. Available Every Minute ... 227.2345 Live Chat Follow Us Twitter Facebook Instagram help site map privacy accessibility terms of use ...

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

    Science.gov (United States)

    2013-01-01

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

  7. p53 protein aggregation promotes platinum resistance in ovarian cancer.

    Science.gov (United States)

    Yang-Hartwich, Y; Soteras, M G; Lin, Z P; Holmberg, J; Sumi, N; Craveiro, V; Liang, M; Romanoff, E; Bingham, J; Garofalo, F; Alvero, A; Mor, G

    2015-07-01

    High-grade serous ovarian carcinoma (HGSOC), the most lethal gynecological cancer, often leads to chemoresistant diseases. The p53 protein is a key transcriptional factor regulating cellular homeostasis. A majority of HGSOCs have inactive p53 because of genetic mutations. However, genetic mutation is not the only cause of p53 inactivation. The aggregation of p53 protein has been discovered in different types of cancers and may be responsible for impairing the normal transcriptional activation and pro-apoptotic functions of p53. We demonstrated that in a unique population of HGSOC cancer cells with cancer stem cell properties, p53 protein aggregation is associated with p53 inactivation and platinum resistance. When these cancer stem cells differentiated into their chemosensitive progeny, they lost tumor-initiating capacity and p53 aggregates. In addition to the association of p53 aggregation and chemoresistance in HGSOC cells, we further demonstrated that the overexpression of a p53-positive regulator, p14ARF, inhibited MDM2-mediated p53 degradation and led to the imbalance of p53 turnover that promoted the formation of p53 aggregates. With in vitro and in vivo models, we demonstrated that the inhibition of p14ARF could suppress p53 aggregation and sensitize cancer cells to platinum treatment. Moreover, by two-dimensional gel electrophoresis and mass spectrometry we discovered that the aggregated p53 may function uniquely by interacting with proteins that are critical for cancer cell survival and tumor progression. Our findings help us understand the poor chemoresponse of a subset of HGSOC patients and suggest p53 aggregation as a new marker for chemoresistance. Our findings also suggest that inhibiting p53 aggregation can reactivate p53 pro-apoptotic function. Therefore, p53 aggregation is a potential therapeutic target for reversing chemoresistance. This is paramount for improving ovarian cancer patients' responses to chemotherapy, and thus increasing their

  8. 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

  9. Organisation and quality of primary surgical intervention for ovarian cancer in Denmark

    DEFF Research Database (Denmark)

    Marx, Charlotte; Bendixen, Anette; Høgdall, Claus

    2007-01-01

    The positive effect on survival of maximal primary cytoreductive surgery for ovarian cancer is well established, and the highest rates of optimal cytoreduction are achieved by gynecological oncologists. Danish women have not only one of the highest incidences of ovarian cancer, but also the highe...

  10. Is centralization of ovarian cancer care warranted? A cost-effectiveness analysis

    NARCIS (Netherlands)

    Greving, Jacoba P.; Vernooji, Flora; Heintz, A. Peter M.; van der Graaf, Yolanda; Buskens, Erik

    2009-01-01

    Objective. To evaluate the cost-effectiveness of tertiary referral care for ovarian cancer patients in the Netherlands. Methods. We collected clinical and registry data on 1077 newly diagnosed ovarian cancer patients treated from 1996-2003 in a random sample of Dutch hospitals. Decision modelling wa

  11. Mumps Parotitis and Ovarian Cancer: Modern Significance of an Historic Association

    Science.gov (United States)

    2009-10-01

    parotitis and subsequent development of ovarian cancer. On June of 2009, we searched MEDLINE (via PubMed), Web of Science and EMBASE using the...association between history of mumps parotitis and subsequent development of ovarian cancer. On June of 2009, we searched MEDLINE (via PubMed), Web of Science and

  12. Breast and ovarian cancers: a survey and possible roles for the cell surface heparan sulfate proteoglycans

    DEFF Research Database (Denmark)

    Yoneda, Atsuko; Lendorf, Maria E; Couchman, John R;

    2012-01-01

    of breast cancer may also develop ovarian cancer. Here, the authors review the different tumor markers of breast and ovarian carcinoma and discuss the expression, mutations, and possible roles of cell surface heparan sulfate proteoglycans during tumorigenesis of these carcinomas. The focus is on two groups...

  13. Seldi-tof MS Profiling of Plasma Proteins in Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Shao-Pai Wu

    2006-03-01

    Conclusion: This study clearly demonstrates that the combined technology of SELDI-TOF MS and artificial intelligence is effective in distinguishing protein expression between normal and ovarian cancer plasma. The identified protein peaks may be candidate proteins for early detection of ovarian cancer or evaluation of therapeutic response.

  14. History of hypertension, heart disease, and diabetes and ovarian cancer patient survival

    DEFF Research Database (Denmark)

    Minlikeeva, Albina N; Freudenheim, Jo L; Cannioto, Rikki A

    2017-01-01

    PURPOSE: Survival following ovarian cancer diagnosis is generally low; understanding factors related to prognosis could be important to optimize treatment. The role of previously diagnosed comorbidities and use of medications for those conditions in relation to prognosis for ovarian cancer patien...

  15. Targeting Cell Surface Proteins in Molecular Photoacoustic Imaging to Detect Ovarian Cancer Early

    Science.gov (United States)

    2013-07-01

    10-1-0422 TITLE: Targeting Cell Surface Proteins in Molecular Photoacoustic Imaging to Detect Ovarian Cancer Early PRINCIPAL...DATES COVERED 1 July 2010 - 30 June 2013 4. TITLE AND SUBTITLE Targeting Cell Surface Proteins in Molecular 5a. CONTRACT NUMBER Photoacoustic ...upon request). Aim 2) Prioritize ovarian cancer-associated surface proteins for their utility as molecular photoacoustic imaging targets and

  16. 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

  17. Olaparib treatment for BRCA-mutant ovarian cancer with leptomeningeal disease.

    Science.gov (United States)

    Bangham, Madeleine; Goldstein, Robert; Walton, Henry; Ledermann, Jonathan A

    2016-11-01

    •Leptomeningeal disease occurs more commonly in BRCA-mutated ovarian cancer.•A clinically significant dose of olaprib is able to penetrate the leptomeninges.•Leptomeningeal metastases in a BRCA-mutated ovarian cancer responded to olaparib.

  18. 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

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  20. Serum tetranectin is a significant prognostic marker in ovarian cancer patients

    DEFF Research Database (Denmark)

    Begum, Farah Diba; Høgdall, Estrid; Christensen, Ib Jarle

    2010-01-01

    To evaluate the prognostic value of preoperative serum tetranectin (TN) in Danish ovarian cancer (OvCa) patients. Design. Population-based, multidisciplinary Danish case-control study of OvCa.......To evaluate the prognostic value of preoperative serum tetranectin (TN) in Danish ovarian cancer (OvCa) patients. Design. Population-based, multidisciplinary Danish case-control study of OvCa....

  1. Specialized care and survival of ovarian cancer patients in The Netherlands: Nationwide cohort study

    NARCIS (Netherlands)

    F. Vernooij (Flora); A.P.M. Heintz (Peter); P.O. Witteveen (Petronella); M. van der Heiden-Van der Loo (Margriet); J.W.W. Coebergh (Jan Willem); Y. van der Graaf (Yolanda)

    2008-01-01

    textabstractBackground: There is much debate on the necessity of regionalization of ovarian cancer care. We investigated the association between hospital type and survival of patients with ovarian cancer in The Netherlands. Methods: A retrospective, population-based cohort study was performed on all

  2. 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,

  3. 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.

  4. 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.

  5. 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

  6. Organisation and quality of primary surgical intervention for ovarian cancer in Denmark

    DEFF Research Database (Denmark)

    Marx, Charlotte; Bendixen, Anette; Høgdall, Claus;

    2007-01-01

    The positive effect on survival of maximal primary cytoreductive surgery for ovarian cancer is well established, and the highest rates of optimal cytoreduction are achieved by gynecological oncologists. Danish women have not only one of the highest incidences of ovarian cancer, but also the highe...

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    Background: Little is known about modifiable behaviours that may be associated with epithelial ovarian cancer (EOC) survival. We conducted a pooled analysis of 12 studies from the Ovarian Cancer Association Consortium to investigate the association between pre-diagnostic physical inactivity and m...

  8. MMP-14 and CD44 in Epithelial-to-Mesenchymal Transition (EMT) in ovarian cancer

    NARCIS (Netherlands)

    Vos, M.C.; Hollemans, E.; Ezendam, N.; Feijen, H.; Boll, D.; Pijlman, B.; Putten, H. van der; Klinkhamer, P.; Kuppevelt, T.H. van; Wurff, A.A. van der; Massuger, L.F.A.G.

    2016-01-01

    BACKGROUND: To investigate the expression of MMP-14 and CD44 as well as epithelial-to-mesenchymal transition(EMT)-like changes in ovarian cancer and to determine correlations with clinical outcome. METHODS: In 97 patients with ovarian cancer, MMP-14 and CD44 expression as determined by immunohistoch

  9. Diurnal cortisol and survival in epithelial ovarian cancer.

    Science.gov (United States)

    Schrepf, Andrew; Thaker, Premal H; Goodheart, Michael J; Bender, David; Slavich, George M; Dahmoush, Laila; Penedo, Frank; DeGeest, Koen; Mendez, Luis; Lubaroff, David M; Cole, Steven W; Sood, Anil K; Lutgendorf, Susan K

    2015-03-01

    Hypothalamic-pituitary-adrenal (HPA) deregulation is commonly observed in cancer patients, but its clinical significance is not well understood. We prospectively examined the association between HPA activity, tumor-associated inflammation, and survival in ovarian cancer patients prior to treatment. Participants were 113 women with ovarian cancer who provided salivary cortisol for three days prior to treatment for calculation of cortisol slope, variability, and night cortisol. Cox proportional hazard regression analyses were used to examine associations between cortisol and survival in models adjusting for disease stage, tumor grade, cytoreduction and age. On a subsample of 41 patients with advanced disease ascites fluid was assayed for levels of interleukin-6 (IL-6) and correlated with cortisol variables. Each cortisol measure was associated with decreased survival time, adjusting for covariates (all pcortisol was associated with a 46% greater likelihood of death. Patients in the high night cortisol group survived an estimated average of 3.3 years compared to 7.3 years for those in the low night cortisol group. Elevated ascites IL-6 was associated with each cortisol measure (all r>36, all pcortisol rhythms assessed prior to treatment are associated with decreased survival in ovarian cancer and increased inflammation in the vicinity of the tumor. HPA abnormalities may reflect poor endogenous control of inflammation, dysregulation caused by tumor-associated inflammation, broad circadian disruption, or some combination of these factors. Nocturnal cortisol may have utility as a non-invasive measure of HPA function and/or disease severity. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Differential BCCIP gene expression in primary human ovarian cancer, renal cell carcinoma and colorectal cancer tissues.

    Science.gov (United States)

    Liu, Xiaoxia; Cao, Lingling; Ni, Jinsong; Liu, Ning; Zhao, Xiaoming; Wang, Yanfang; Zhu, Lin; Wang, Lingyao; Wang, Jin; Yue, Ying; Cai, Yong; Jin, Jingji

    2013-12-01

    Human BCCIP, a protein which interacts with BRCA2 and CDKN1A (Cip1, p21), has been implicated in many cellular processes including cell cycle regulation, DNA recombination and damage repair, telomere maintenance, embryonic development and genomic stability. BCCIP gene expression, which is an important BRCA2 cofactor in tumor suppression, has been identified in some primary cancers. Thus, we investigated the role of BCCIP expression in a large sample of clinically diagnosed primary ovarian cancer, renal cell carcinoma (RCC) and colorectal cancer (CRC) tissues. Using clinically diagnosed frozen primary cancer tissues, quantitative PCR (qPCR), western blot analysis (WB) and immunohistochemical staining (IHC) approaches were used to detect and measure gene expression. Reduced BCCIP gene expression in ovarian cancer, RCC and CRC tissues occurred in 74, 89 and 75% of tissue samples, respectively. qPCR analysis of mRNA expression in 54 ovarian cancer, 50 RCC and 44 CRC samples revealed significant (>2-fold decreased) BCCIP downregulation in 56, 70 and 46% of tissue samples, respectively. Although BCCIP expression in three different tumor tissues decreased, the relationship between BCCIP expression and clinicopathological features of each cancer was distinct. Compared to normal tissues, BCCIP expression in ovarian cancers was significantly downregulated in serous, endometrioid and mucinous carcinomas. Downregulation of BCCIP expression was strongly associated with clear cell RCC (ccRCC) and Fuhrman tumor grading, but significant differences in BCCIP expression between CRC and matched normal tissues occurred only in male CRC tissues (ptissue with a T4 tumor stage (ptissue samples (phuman ovarian cancer, RCC and CRC tissues, suggesting a role for the gene in the pathogenesis of these cancers.

  11. Completeness of pedigree and family cancer history for ovarian cancer patients.

    Science.gov (United States)

    Son, Yedong; Lim, Myong Cheol; Seo, Sang Soo; Kang, Sokbom; Park, Sang Yoon

    2014-10-01

    To investigate the completeness of pedigree and of number of pedigree analysis to know the acceptable familial history in Korean women with ovarian cancer. Interview was conducted in 50 ovarian cancer patients for obtaining familial history three times over the 6 weeks. The completeness of pedigree is estimated in terms of familial history of disease (cancer), health status (health living, disease and death), and onset age of disease and death. The completion of pedigree was 79.3, 85.1, and 85.6% at the 1st, 2nd, and 3rd time of interview and the time for pedigree analysis was 34.3, 10.8, and 3.1 minutes, respectively. The factors limiting pedigree analysis were as follows: out of contact with their relatives (38%), no living ancestors who know the family history (34%), dispersed family member because of the Korean War (16%), unknown cause of death (12%), reluctance to ask medical history of relatives (10%), and concealing their ovarian cancer (10%). The percentage of cancers revealed in 1st (2%) and 2nd degree (8%) relatives were increasing through surveys, especially colorectal cancer related with Lynch syndrome (4%). Analysis of pedigree at least two times is acceptable in Korean woman with ovarian cancer from the first study. The completion of pedigree is increasing, while time to take family history is decreasing during three time survey.

  12. [Paraneoplastic cerebellar degeneration associated with ovarian cancer: anti-Yo immunoreactivity in autoptic cerebellum and ovarian carcinoma].

    Science.gov (United States)

    Bartos, A; Stourac, P; Rusina, R; Sejdová, M; Velenská, Z

    2002-10-01

    Paraneoplastic cerebellar degeneration is a rare disorder caused likely by autoimmune mechanisms in malignant oncologic diseases, and the most common tumors are ovarian, breast, lung cancer, and m. Hodgkin. An immune reaction is supposed to be directed against identical antigens of cerebellum and tumor, and paraneoplastic antibodies called anti-Yo, anti-Hu, anti-Ri, or anti-Tr are often detected in blood and cerebrospinal fluid. The course of paraneoplastic cerebellar degeneration as a complication of ovarian cancer is described. The relationship between the malignancy and pathologic changes in cerebellum was confirmed by positive immunohistochemical and immunofluorescence reaction between a patient's anti-Yo-positive serum and her own Purkinje's and ovarian cancer cells.

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

    Science.gov (United States)

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

  14. 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.

  15. Women with BRCA1 and BRCA2 mutations survive ovarian cancer at higher rates

    Science.gov (United States)

    Results from a National Cancer Institute (NCI) sponsored multicenter study published in the Journal of the American Medical Association on January 25, 2012, provides strong evidence that BRCA1 and BRCA2 gene mutation carriers with ovarian cancer were more

  16. Polymorphic variation of genes in the fibrinolytic system and the risk of ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Yaakov Bentov

    Full Text Available INTRODUCTION: The etiology of ovarian cancer is largely unknown. One hypothesis is that the inefficient removal of the blood clots and fibrin products which are deposited in the vicinity of the ovary by retrograde menstruation might be associated with an increased risk of ovarian cancer. Several single nucleotide polymorphisms within genes which comprise the fibrinolytic system have been shown to have functional effects on the rate of blood clot degradation. These were considered to be candidate genes in the present study. AIM: We studied the genotype distributions of 12 functional SNPs of four genes (tPA, uPA PAI1 and TAFI among 775 ovarian cancer cases and 889 controls. RESULTS: No significant associations were seen between any of the ten SNPs and the risk of ovarian cancer as a whole, or in any histologic subgroup. DISCUSSION: Germline known functional variants of genes in the fibrinolytic system are not associated with risk of ovarian cancer.

  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

    It has been suggested that paracetamol reduces the risk for ovarian cancer. We examined the association between prescription use of paracetamol and ovarian cancer risk in a nationwide case-control study nested within the Danish female population. Case patients (n = 3471) were all women with a first......% 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. 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 small number of studies. METHODS: We used data on 2,281 BRCA1 carriers and 1,038 BRCA2 carriers from the International BRCA1/2 Carrier Cohort Study to evaluate the effect of reproductive and hormonal factors on ovarian cancer risk for mutation carriers. Data were analyzed within a weighted Cox...... proportional hazards framework. RESULTS: There were no significant differences in the risk of ovarian cancer between parous and nulliparous carriers. For parous BRCA1 mutation carriers, the risk of ovarian cancer was reduced with each additional full-term pregnancy (P trend = 0.002). BRCA1 carriers who had...

  19. Overexpression of receptor for advanced glycation end products (RAGE) in ovarian cancer.

    Science.gov (United States)

    Rahimi, Farzaneh; Karimi, Jamshid; Goodarzi, Mohammad Taghi; Saidijam, Massoud; Khodadadi, Iraj; Razavi, Amir Nader Emami; Nankali, Maryam

    2017-01-01

    Ovarian cancer is one of the important challenges in the field of gynecologic oncology because of some problems in understanding its etiology and pathogenesis. Receptor for advanced glycation end products (RAGE) is a multiligand trans-membranous receptor which is upregulated in some human cancers. Mechanisms of RAGE involvement in carcinogenesis of ovarian cancer are unknown. This study aimed to investigate the expression of RAGE in ovarian cancers and its association with clinicopathological characteristics. The RAGE expression level in ovarian cancer and corresponding noncancerous tissues were analyzed by real time quantitative RT-PCR and immunohistochemistry techniques. Results indicated that RAGE gene was overexpressed in ovarian cancer tissue compared with adjacent noncancerous tissue (p RAGE expression and tumor size (p = 0.04), depth of stromal invasion (p = 0.031), lymphovascular invasion (p = 0.041) and stage of cancer (p = 0.041) was observed. The receiver operating characteristic (ROC) analyses yielded the area under the curve (AUC) values of 0.86 for RAGE in discriminating ovarian cancer samples from non-cancer controls. In conclusion overexpression of RAGE in ovarian cancer may be a useful biomarker to predict tumor progression.

  20. 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.

  1. Ovarian cancer risk and nonisoflavone flavonoids intake: A systematic review of epidemiological studies

    Science.gov (United States)

    Mohammadi, Vida; Dehghani, Sirous; Larijani, Bagher; Azadbakht, Leila

    2016-01-01

    Background: Although several studies have investigated the association between ovarian cancer risk and nonisoflavone flavonoids intake, these findings are inconsistent. This systematic review of published epidemiological studies was conducted to summarize and clarify the evidence on the association between ovarian cancer incidence and nonisoflavone flavonoids intake. Materials and Methods: PubMed, Scopus, Google Scholar, and EMBASE databases were searched based on MeSH term (ovarian neoplasm in combination with flavonoids) to identify related English and non-English papers published up to June 2016. We summarized the results of the relevant studies in this review. Results: In total, seven studies (four with cohort and three with case–control design) included in this review. The results of conducted cohort studies show no relation between ovarian cancer risk and total nonisoflavone flavonoids intake, and only one study reported a significant reduction between ovarian cancer incidence and kaempferol and luteolin intake. Similar to those in the cohort studies, also in case–control studies, no association was found between total nonisoflavone flavonoids intake and ovarian cancer risk, just an inverse association between flavonols intake and ovarian cancer was reported. Conclusion: Several studies investigated the relation of nonisoflavone flavonoids intake and ovarian cancer risk; none of them reported any association for total nonisoflavone flavonoids intake, but some reported an inverse association between certain subclasses or individual flavonoids. These findings are limited, and there is a need for further and more accurate researches to be confirmed.

  2. 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.

  3. Connective tissue growth factor as a novel therapeutic target in high grade serous ovarian cancer

    Science.gov (United States)

    Moran-Jones, Kim; Gloss, Brian S.; Murali, Rajmohan; Chang, David K.; Colvin, Emily K.; Jones, Marc D.; Yuen, Samuel; Howell, Viive M.; Brown, Laura M.; Wong, Carol W.; Spong, Suzanne M.; Scarlett, Christopher J.; Hacker, Neville F.; Ghosh, Sue; Mok, Samuel C.; Birrer, Michael J.; Samimi, Goli

    2015-01-01

    Ovarian cancer is the most common cause of death among women with gynecologic cancer. We examined molecular profiles of fibroblasts from normal ovary and high-grade serous ovarian tumors to identify novel therapeutic targets involved in tumor progression. We identified 2,300 genes that are significantly differentially expressed in tumor-associated fibroblasts. Fibroblast expression of one of these genes, connective tissue growth factor (CTGF), was confirmed by immunohistochemistry. CTGF protein expression in ovarian tumor fibroblasts significantly correlated with gene expression levels. CTGF is a secreted component of the tumor microenvironment and is being pursued as a therapeutic target in pancreatic cancer. We examined its effect in in vitro and ex vivo ovarian cancer models, and examined associations between CTGF expression and clinico-pathologic characteristics in patients. CTGF promotes migration and peritoneal adhesion of ovarian cancer cells. These effects are abrogated by FG-3019, a human monoclonal antibody against CTGF, currently under clinical investigation as a therapeutic agent. Immunohistochemical analyses of high-grade serous ovarian tumors reveal that the highest level of tumor stromal CTGF expression was correlated with the poorest prognosis. Our findings identify CTGF as a promoter of peritoneal adhesion, likely to mediate metastasis, and a potential therapeutic target in high-grade serous ovarian cancer. These results warrant further studies into the therapeutic efficacy of FG-3019 in high-grade serous ovarian cancer. PMID:26575166

  4. MicroRNA-181b promotes ovarian cancer cell growth and invasion by targeting LATS2

    Energy Technology Data Exchange (ETDEWEB)

    Xia, Ying; Gao, Yan, E-mail: gaoyanhdhos@126.com

    2014-05-09

    Highlights: • miR-181b is upregulated in human ovarian cancer tissues. • miR-181b promotes ovarian cancer cell proliferation and invasion. • LATS2 is a direct target of miR-181b. • LATS2 is involved in miR-181b-induced ovarian cancer cell growth and invasion. - Abstract: MicroRNAs (miRNAs) are strongly implicated in tumorigenesis and metastasis. In this study, we showed significant upregulation of miR-181b in ovarian cancer tissues, compared with the normal ovarian counterparts. Forced expression of miR-181b led to remarkably enhanced proliferation and invasion of ovarian cancer cells while its knockdown induced significant suppression of these cellular events. The tumor suppressor gene, LATS2 (large tumor suppressor 2), was further identified as a novel direct target of miR-181b. Specifically, miR-181b bound directly to the 3′-untranslated region (UTR) of LATS2 and suppressed its expression. Restoration of LATS2 expression partially reversed the oncogenic effects of miR-181b. Our results indicate that miR-181b promotes proliferation and invasion by targeting LATS2 in ovarian cancer cells. These findings support the utility of miR-181b as a potential diagnostic and therapeutic target for ovarian cancer.

  5. 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

  6. Development of the Ovarian Cancer Cohort Consortium: Risk Factor Associations by Heterogeneity of Disease

    Science.gov (United States)

    2015-10-01

    Breast Cancer Association Consortium studies. J Natl Cancer Inst 2011 February 2;103(3):250-63. (24) Comprehensive molecular portraits of human breast...9609):303-14. 5. Adami HO, Hsieh CC, Lambe M, Trichopoulos D, Leon D, Persson I, et al. Parity, age at first childbirth , and risk of ovarian cancer... human genetics 1989;45(4):521-9. 9. Beral V, Bull D, Green J, Reeves G. Ovarian cancer and hormone replacement therapy in the Million Women Study

  7. 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.

  8. Palliative care in patients with ovarian cancer and bowel obstruction.

    Science.gov (United States)

    Daniele, Alberto; Ferrero, A; Fuso, L; Mineccia, M; Porcellana, V; Vassallo, D; Biglia, N; Menato, G

    2015-11-01

    Malignant bowel obstruction (MBO) is usually a pre-terminal event in patients with ovarian cancer. However, because of the lack of data in literature, decisions around surgical intervention, non-resectional procedures, or medical treatment of MBO in patients with ovarian cancer cannot be lightly undertaken. We analyzed medical and surgical procedures, performance status, nutritional status, cachexia, and their prognostic value in this group of patients. We retrospectively selected all consecutive patients with recurrent ovarian cancer who received medical or surgical treatment for MBO between October 2008 and January 2014 at the Academic Department of Gynecological Oncology of Mauriziano Hospital of Turin (Italy). We found 40 patients: 18 of them underwent medical treatment and 22 of them were submitted to surgery. In the group of surgery, the hospitalization was shorter (p 0.02), the pain reduction was more effective (p 0.001), the number of chemotherapy lines was higher (p 0.03), and re-obstruction was more rare (p 0.02). Between the two groups, we did not find any differences in post-palliation episodes of vomit (p 0.83), type of diet (p 0.34), ability to return home (p 0.72), and death setting (p 0.28). Median survival after palliation was longer in the group of surgery (p 0.025). Cachexia, low performance status, and poor nutritional status were significant predictors of worse survival after MBO, independently by the treatment. Surgery has to be considered in patients without serious contraindications; otherwise, a medical protocol, including antisecretory drugs, is the standard of care in frail patients.

  9. Identifying candidate driver genes by integrative ovarian cancer genomics data

    Science.gov (United States)

    Lu, Xinguo; Lu, Jibo

    2017-08-01

    Integrative analysis of molecular mechanics underlying cancer can distinguish interactions that cannot be revealed based on one kind of data for the appropriate diagnosis and treatment of cancer patients. Tumor samples exhibit heterogeneity in omics data, such as somatic mutations, Copy Number Variations CNVs), gene expression profiles and so on. In this paper we combined gene co-expression modules and mutation modulators separately in tumor patients to obtain the candidate driver genes for resistant and sensitive tumor from the heterogeneous data. The final list of modulators identified are well known in biological processes associated with ovarian cancer, such as CCL17, CACTIN, CCL16, CCL22, APOB, KDF1, CCL11, HNF1B, LRG1, MED1 and so on, which can help to facilitate the discovery of biomarkers, molecular diagnostics, and drug discovery.

  10. 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.

  11. A murine model for bladder cancer.

    Science.gov (United States)

    Murphy, G P; Sandberg, A A; Pontes, J E; Ochi, H; Yoshida, M; Williams, P D

    1984-01-01

    Growth characteristics, survival time, and various other parameters such as chromosome studies and DNA synthesis were evaluated in a transplantable transitional cell mouse bladder tumor induced by N-[4-5-nitro-2-furyl)-2-thiazolyl] formamide (FANFT). When the tumor was implanted subcutaneously, the mice were observed to survive mean 43 + 7 days (mean +/- SEM) with an average tumor burden of mean 8.45 +/- 0.60 gm (mean +/- SEM) of solid tumor tissue. In the tumor control animals, lung metastasis was noted in 3 animals at 42-49 days post implantation. The histological appearance of the primary tumor and the lung metastasis presented an undifferentiated anaplastic tumor with many spindle cells. The modal number of chromosome is 65 with several markers identifiable as abnormal in morphology. A significant decrease (p less than 0.001) in DNA synthesis was noted between 13 days and 20 days post implantation. In the evaluation of chemotherapy drugs, Cis-dichloro-trans-dihydroxy-bis-iso propylamine platinum IV (CHIP), Cis-diaminedichloroplatinum II (DDP), Cyclophosphamide (CTX) and Methotrexate (MTX) tumor growth was significantly retarded (p less than 0.005) in the DDP treated groups, however survival was not improved. Survival was significantly improved in the CTX treated group (p less than 0.001), although no significant decrease was noted in tumor growth. Lung metastasis was noted in all groups. This model has certain characteristics which make it a good model to study locally invasive bladder cancer.

  12. 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

  13. Ovarian cancer: progress and continuing controversies in management.

    Science.gov (United States)

    Moss, Charlotte; Kaye, Stan B

    2002-09-01

    Ovarian cancer is the most lethal of the gynaecological cancers, affecting approximately 1 in 75 women in the developed world. In most cases (>75%), the disease is disseminated beyond the ovary at diagnosis. For patients with stage III-IV disease, many clinicians agree that standard treatment should comprise six cycles of paclitaxel-carboplatin. Randomised trials over the past 10 years have indicated the superiority of paclitaxel-based treatment and that carboplatin is equivalent to cisplatin, but better tolerated. A recent trial has suggested that docetaxel may be a better option than paclitaxel, with reduced neurotoxicity and comparable efficacy. Overall treatment results remain unsatisfactory, since the median survival for these patients is 2-3 years. Future progress may be made by addressing the following issues: Would sequential regimes be more effective? Intriguing results from two large randomised trials (ICON-3 and GOG-132) indicate that single agent platinum might well be incorporated into such regimes. Additionally, a range of other agents could be tested as part of first-line regimes, having demonstrated activity in relapsed patients; these include topotecan, gemcitabine and liposomal doxorubicin. Newer agents, such as cell signalling inhibitors have shown potential as single agents, but may be particularly effective in combination with current drugs. Real progress can be expected when a better understanding is achieved of the mechanisms underlying clinical drug resistance in ovarian cancer, and a close laboratory-clinical interaction is crucial.

  14. 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.

  15. Therapeutic Strategies against Cyclin E1-Amplified Ovarian Cancers

    Science.gov (United States)

    2016-10-01

    resistance to platinum, management of CCNE1- amplified ovarian cancers is challenging. In this research, we evaluate three novel strategies against CCNE1...associated with poor outcome and inferior responsiveness to standard platinum chemotherapy. Given their intrinsic resistance to platinum, management of...1 4. Impact…………………………...…………………………………… 9 5. Changes /Problems...….……………………………………………… 10 6. Products

  16. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  18. Functional Proteomics-Based Ovarian Cancer Biomarkers

    Science.gov (United States)

    2010-11-01

    that regulates breast cancer cell motility by modulating the actin cytoskeleton." European journal of cell biology 88.6 (2009): 325. 70  Jones, Neil A...the ovary in a patient with Waardenburg syndrome." American journal of Ophthalmology 133.5 (2002): 716-718. 110  Moshfeghi, Darius M., et al...34Retinoblastoma metastatic to the ovary in a patient with Waardenburg syndrome." American journal of Ophthalmology 133.5 (2002): 716-718. 111  Nagashima

  19. Pegylated liposomal doxorubicin in ovarian cancer

    OpenAIRE

    Matei, Daniela

    2009-01-01

    Robert Strother1,2, Daniela Matei1–51Department of Medicine, 2Indiana University Melvin and Bren Simon Cancer Center, 3Department of Obstetrics and Gynecology, 4Department of Biochemistry and Molecular Biology, 5VA Roudebush Hospital Indiana University School of Medicine, 535 Barnhill Drive, Indianapolis, IN, 46202Abstract: The encapsulation of doxorubicin in a pegylated liposomal matrix led to a reformulated agent with a different toxicity profile and improved clinical utility. Lip...

  20. Androgen receptor gene CAG repeat polymorphism and ovarian cancer risk: A meta-analysis.

    Science.gov (United States)

    Deng, Yang; Wang, Jue; Wang, Ling; Du, Yan

    2017-02-28

    Ovarian cancer is one of the common gynecological malignancies worldwide. It is usually diagnosed at a later stage, thus missing the best opportunity for treatment. Despite the advancement of ovarian cancer treatment, the prognosis is still poor. Androgen receptor (AR) may play a role in ovarian carcinogenesis. Previous studies regarding the association between AR CAG repeat length and ovarian cancer risk reported inconsistent results. Therefore, we conducted a meta-analysis to evaluate the association between AR CAG repeat length and ovarian cancer risk following the MOOSE guidelines. PubMed, Web of Science, EBSCO and other databases were searched up to September 15(th) 2016. Case control studies with clear definition of CAG repeat length and detailed genotype information were included. Two authors independently reviewed and extracted data. Pooled analysis and subgroup analysis stratified by ethnicity were performed for different genetic models. Begg's funnel plot and Egger's test were performed for publication bias estimation. Overall, there was no association between the AR CAG repeat polymorphism and ovarian cancer risk. However, short CAG repeat polymorphism was associated with increased ovarian cancer risk in African Americans and Chinese under the dominant model, whereas a reverse association was observed in Caucasians and Italians under the other three models. Our study results should be interpreted with caution. Further well-designed epidemiological and functional studies are needed to elucidate the role of AR in ovarian carcinogenesis.

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

    Science.gov (United States)

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

    2015-05-30

    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 prosurvival genes. We suggest that addition of ibrutinib to cisplatin may improve treatment outcome in ovarian cancer.

  2. Coffee, tea, and caffeine consumption and risk of epithelial ovarian cancer and borderline ovarian tumors: Results from a Danish case-control study.

    Science.gov (United States)

    Gosvig, Camilla F; Kjaer, Susanne K; Blaakær, Jan; Høgdall, Estrid; Høgdall, Claus; Jensen, Allan

    2015-01-01

    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. From 1995 through 1999, we included 267 women with ovarian cancer, 115 women with borderline ovarian tumors and 911 randomly selected control women. All women completed a beverage frequency questionnaire with detailed information on coffee and tea consumption. Analyses were performed using multiple logistic regression models. 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. No relation between tea consumption and ovarian cancer risk was observed. The risk estimates for borderline ovarian tumors resembled those observed for ovarian cancer, but did not reach statistical significance. Our results indicate that coffee consumption and total caffeine consumption from coffee and tea combined is associated with a modest decreased risk of ovarian cancer. However, more biological studies are needed to identify bioactive chemical compounds in coffee that potentially could affect ovarian cancer development.

  3. Epidemiology of Patients with Ovarian Cancer with and Without a BRCA1/2 Mutation.

    Science.gov (United States)

    Weiderpass, Elisabete; Tyczynski, Jerzy E

    2015-12-01

    Ovarian cancer survival rates have improved only slightly in recent decades; however, treatment of this disease is expected to undergo rapid change as strategies incorporating molecular-targeted therapies enter clinical practice. Carriers of deleterious mutations (defined as a harmful mutation) in either the BRCA1 or BRCA2 gene (BRCAm) have a significantly increased risk of developing ovarian cancer. Epidemiology data in large (>500 patients) unselected ovarian cancer populations suggest that the expected incidence rate for BRCAm in this population is 12-14 %. Patients with a BRCAm are typically diagnosed at a younger age than those without a BRCAm. Associations with BRCAm vary according to ethnicity, with women of Ashkenazi Jewish descent being 10 times more likely to have a BRCAm than the general population. In terms of survival, patients with invasive epithelial ovarian cancer who have a BRCAm may have improved overall survival compared with patients who do not carry a BRCAm. Although genetic testing for BRCAm remains relatively uncommon in ovarian cancer patients, testing is becoming cheaper and increasingly accessible; however, this approach is not without numerous social, ethical and policy issues. Current guidelines recommend BRCAm testing in specific ovarian cancer patients only; however, with the emergence of treatments that are targeted at patients with a BRCAm, genetic testing of all patients with high-grade serous ovarian cancer may lead to improved patient outcomes in this patient population. Knowledge of BRCAm status could, therefore, help to inform treatment decisions and identify relatives at increased risk of developing cancer.

  4. Profile of bevacizumab in the treatment of platinum-resistant ovarian cancer: current perspectives

    Directory of Open Access Journals (Sweden)

    McClung EC

    2016-03-01

    Full Text Available E Clair McClung, Robert M WenhamDepartment of Gynecologic Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USAAbstract: Patients with platinum-resistant ovarian cancer have progression of disease within 6 months of completing platinum-based chemotherapy. While several chemotherapeutic options exist for the treatment of platinum-resistant ovarian cancer, the overall response to any of these therapies is ~10%, with a median progression-free survival of 3–4 months and a median overall survival of 9–12 months. Bevacizumab (Avastin, a humanized, monoclonal antivascular endothelial growth factor antibody, has demonstrated antitumor activity in the platinum-resistant setting and was recently approved by US Food and Drug Administration for combination therapy with weekly paclitaxel, pegylated liposomal doxorubicin, or topotecan. This review summarizes key clinical trials investigating bevacizumab for recurrent, platinum-resistant ovarian cancer and provides an overview of efficacy, safety, and quality of life data relevant in this setting. While bevacizumab is currently the most studied and clinically available antiangiogenic therapy, we summarize recent studies highlighting novel alternatives, including vascular endothelial growth factor-trap, tyrosine kinase inhibitors, and angiopoietin inhibitor trebananib, and discuss their application for the treatment of platinum-resistant ovarian cancer.Keywords: bevacizumab, angiogenesis, ovarian cancer, platinum-resistant ovarian cancer, recurrent ovarian cancer

  5. DETECTION OF OXIDATIVE STRESS, APOPTOSIS AND MOLECULAR LESIONS IN HUMAN OVARIAN CANCER CELLS

    Directory of Open Access Journals (Sweden)

    H. I. Falfushynska

    2016-05-01

    Full Text Available Background. Ovarian cancer has the highest mortality rate of gynaecological cancers. This is partly due to the lack of effective screening markers. Indices of oxidative stress are well-recognized prognostic criteria for tumorous transformation of tissue, but their value depends on the type of tumor and the stage of its development. Objective. The aim of this study is to clarify the relationship between antioxidant/pro-oxidant ratio and the signs of molecular lesions and apoptosis rate in blood of ovarian cancer patients and non-cancer ones. Results. The ovarian cancer group is marked by antioxidant/prooxidant balance shifting to oxidative damage in blood as the consequence of overexpression of oxyradicals (by 300%. Higher level of glutathione (by 366%, lower level of metallothioneins (by 65% as well as higher level of lipid peroxidation (by 174% and protein carbonyls (by 186% in blood of ovarian cancer patients compared to the normal ovarian group have been observed. The signs of cytotoxicity are determined in blood of ovarian cancer patients: an increased (compared to control level of DNA fragmentation (by 160%, choline esterase (up to twice, higher rate of both caspase dependent and caspase independent lysosomal mediated apoptosis. Conclusions. Cathepsin D activity both total and free, choline esterase activity, TBA-reactive substance and protein carbonyls level in blood could be used as the predictive markers of worse prognosis and the signs of human ovarian cancer.

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

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    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.

  7. High-grade ovarian cancer secreting effective exosomes in tumor angiogenesis.

    Science.gov (United States)

    Yi, Huan; Ye, Jun; Yang, Xiao-Mei; Zhang, Li-Wen; Zhang, Zhi-Gang; Chen, Ya-Ping

    2015-01-01

    Ovarian cancer, the most lethal gynecological cancer, related closely to tumor stage. High-grade ovarian cancer always results in a late diagnose and high recurrence, which reduce survival within five years. Until recently, curable therapy is still under research and anti-angiogenesis proves a promising way. Tumor-derived exosomes are essential in tumor migration and metastases such as angiogenesis is enhanced by exosomes. In our study, we have made comparison between high-grade and unlikely high-grade serous ovarian cancer cells on exosomal function of endothelial cells proliferation, migration and tube formation. Exosomes derived from high-grade ovarian cancer have a profound impact on angiogenesis with comparison to unlikely high-grade ovarian cancer. Proteomic profiles revealed some potential proteins involved in exosomal function of angiogenesis such as ATF2, MTA1, ROCK1/2 and so on. Therefore, exosomes plays an influential role in angiogenesis in ovarian serous cancer and also function more effectively in high-grade ovarian cancer cells.

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

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    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.

  10. 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.

  11. Quality of life and sexuality comparison between sexually active ovarian cancer survivors and healthy women

    Science.gov (United States)

    Kim, Se Ik; Lee, Yumi; Joo, Jungnam; Park, KiByung; Lee, Dong Ock; Park, Sang-Yoon

    2015-01-01

    Objective compare quality of life (QoL) and sexual functioning between sexually active ovarian cancer survivors and healthy women. Methods A cross-sectional study was performed in 103 successfully treated ovarian cancer survivors and 220 healthy women. All women had engaged in sexual activity within the previous 3 months, and ovarian cancer survivors were under surveillance after primary treatment without evidence of disease. QoL and sexual functioning were assessed using three questionnaires; the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), Ovarian Cancer Module (EORTC QLQ-OV28), and the Female Sexual Function Index (FSFI). Propensity score matching was used to adjust covariates between the ovarian cancer survivor and healthy women groups. In total, 73 ovarian cancer survivors and 73 healthy women were compared. Results Poorer social functioning (mean, 82.4 vs. 90.9; p=0.010) and more financial difficulties (mean, 16.4 vs. 7.8; p=0.019) were observed among ovarian cancer survivors than among healthy women. Sexuality, both in terms of desire, arousal, lubrication, orgasm, satisfaction, and pain and in terms of interest in sex, sexual activity, and enjoyment of sex (EORTC QLQ-OV28) were similar between the groups. However, vaginal dryness was more problematic in ovarian cancer survivors, with borderline statistical significance (p=0.081). Conclusion Sexuality was not impaired in ovarian cancer survivors who were without evidence of disease after primary treatment and having sexual activities, compared with healthy women, whereas social functioning and financial status did deteriorate. Prospective cohort studies are needed. PMID:25686396

  12. Mass spectrometric profiling reveals association of N-glycan patterns with epithelial ovarian cancer progression.

    Science.gov (United States)

    Chen, Huanhuan; Deng, Zaian; Huang, Chuncui; Wu, Hongmei; Zhao, Xia; Li, Yan

    2017-07-01

    Aberrant changes of N-glycan modifications on proteins have been linked to various diseases including different cancers, suggesting possible avenue for exploring their etiologies based on N-glycomic analysis. Changes in N-glycan patterns during epithelial ovarian cancer development have so far been investigated mainly using serum, plasma, ascites, and cell lines. However, changes in patterns of N-glycans in tumor tissues during epithelial ovarian cancer progression have remained largely undefined. To investigate whether changes in N-glycan patterns correlate with oncogenesis and progression of epithelial ovarian cancer, we profiled N-glycans from formalin-fixed paraffin-embedded tissue slides using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and quantitatively compared among different pathological grades of epithelial ovarian cancer and healthy controls. Our results show that among the 80 compositions of N-glycan detected, expression levels of high-mannose type were higher in epithelial ovarian cancer samples than that observed in healthy controls, accompanied by reduced levels of hybrid-type glycans. By applying receiver operating characteristic analysis, we show that a combined panel composed of four high-mannose and three fucosylated neutral complex N-glycans allows for good discrimination of epithelial ovarian cancer from healthy controls. Furthermore, using a statistical analysis of variance assay, we found that different N-glycan patterns, including 2 high-mannose-type, 2 fucosylated and sialylated complex structures, and 10 fucosylated neutral complex N-glycans, exhibited specific changes in N-glycan abundance across epithelial ovarian cancer grades. Together, our results provide strong evidence that N-glycomic changes are a strong indicator for epithelial ovarian cancer pathological grades and should provide avenues to identify novel biomarkers for epithelial ovarian cancer diagnosis and monitoring.

  13. Regulation and Impact of Cytoplasmic ARID1A in Ovarian Cancer

    Science.gov (United States)

    2016-03-01

    5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Thomas P. Conrads, PhD 5d. PROJECT NUMBER 5e. TASK NUMBER E-Mail: thomas.conrads@inova.org 5f. WORK...ABSTRACT Unclassified c. THIS PAGE Unclassified Unclassified 6 19b. TELEPHONE NUMBER (include area code ) Standard Form 298 (Rev. 8-98...protein 1A; tumor suppressor; ovarian cancer; SWI/SNF – switch /sucrose non-fermentable complex; ovarian clear cell carcinoma; endometrioid ovarian

  14. [Vaginal sonography: a screening method for early detection of ovarian tumors and endometrial cancers?].

    Science.gov (United States)

    Osmers, R; Völksen, M; Rath, W; Kuhn, W

    1989-01-01

    In total we performed a vaginosonographic measurement of 212 patients with or without a postmenopausal bleeding. Altogether 424 ovaries were sonographically examined. An endometrial thickness greater than 4 mm was histologically clarified by means of a curettage and all detectable ovarian tumors by means of a laparotomia. In total we found seven asymptomatic endometrial carcinomas, one cervical carcinoma and two ovarian cancers. The vaginosonography showed to be a very sensitive and acceptable method for the early detection of postmenopausal ovarian and endometrial tumors.

  15. Targeting Midbodies in Ovarian Cancer Stem Cells as a Therapeutic Strategy

    Science.gov (United States)

    2013-10-01

    can be retained, accumulated and increased with tumor grade . The long-term goal of this project is to identify putative MB-containing ovarian cancer...increase with increasing ovarian tumor grade . During these analyses, we unexpectedly discovered that a large number of canonical ovarian oncogenes...software was used for equipment control, image acquisition, and image analysis. Tracking Vesicle Movement GFP-FIP3 particles were semiautomatically

  16. 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 ...

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

    Science.gov (United States)

    Rosendahl, Mikkel; Timmermans Wielenga, Vera; Nedergaard, Lotte; Kristensen, Stine Gry; Ernst, Erik; Rasmussen, Per Emil; Anderson, Michael; Schmidt, Kirsten Tryde; Andersen, Claus Yding

    2011-05-01

    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 are required, including xenotransplantation studies. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  18. Mifepristone Inhibits Ovarian Cancer Cancer Cell Growth In Vitro and In Vivo

    Science.gov (United States)

    Goyeneche, Alicia A.; Carón, Rubén W.; Telleria, Carlos M.

    2008-01-01

    Purpose These studies were designed to determine whether the synthetic steroid mifepristone inhibits ovarian cancer growth in vitro and in vivo and the molecular mechanisms involved. Experimental Design The effect of mifepristone on ovarian cancer cell growth in vitro was studied in ovarian cancer cell lines of different genetic backgrounds (SK-OV-3, Caov-3, OV2008, and IGROV-1). In addition, the growth inhibition capacity of mifepristone on ovarian carcinoma xenografts was tested in nude mice. Results Mifepristone inhibited ovarian cancer cell proliferation in a dose- and time-dependent manner. The cytostatic effect of mifepristone was confirmed in a clonogenic survival assay and was not linked to loss of viability. Mifepristone blocked DNA synthesis, arrested the cell cycle at the G1-to-S transition, up-regulated cyclin-dependent kinase (cdk) inhibitors p21cip1 and p27kip1, down-regulated transcription factor E2F1, decreased expression of the E2F1 regulated genes, cdk1 (cdc2) and cyclin A, and modestly decreased cdk2 and cyclin E levels. The abrupt arrest in cell growth induced by mifepristone correlated with reduced cdk2 activity, increased association of cdk2 with p21cip1 and p27kip1, increased nuclear localization of the cdk inhibitors, and reduced nuclear abundance of cdk2 and cyclin E. In vivo, mifepristone significantly delayed the growth of ovarian carcinoma xenografts in a dose-dependent manner and without apparent toxic effects for the animals. Conclusions These preclinical studies demonstrate that mifepristone is effective as a single agent in vitro and in vivo, inhibiting the growth of human epithelial ovarian cancer cells. Mifepristone markedly reduces cdk2 activity likely due to increased association of cdk2 with the cdk inhibitors p21cip1 and p27kip1 and reduced nuclear cdk2/cyclin E complex availability. Acting as a cytostatic agent mifepristone promises to be of translational significance in ovarian cancer therapeutics. PMID:17545545

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

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    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.

  20. CHARACTERISTICS OF CLINICAL COURSE OF METASTATIC AND PRIMARY OVARIAN TUMORS IN COLON CANCER

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    I. A. Dzhanyan

    2015-01-01

    Full Text Available The aim of this study was to investigate clinical pecuiliarities of ovarian tumors in colon cancer patients and determination of complex diagnostic methods.Subject and methods. Russian N.N.  Blokhin Cancer Research Center archives were used for retrospective study, patients, who underwent treatment during 1989–2013  were included. Colon cancer patients with ovarian metastases and with synchronous or metachronous tumors were included.Results. 141 patients were included: 91 patients had colon cancer with ovarian metastases (group 1 and 50 patients had synchronous or metachronous ovarian tumours (group 2. Ovarian tumors were diagnosed during the 1 year in 74 (81.3 % patients in group 1 and in 23 (46 % in group 2. Patients in group 2 less frequently had children (9 (18.0 % vs 5 (5.5 + 2.3 %, р < 0.05, family history of cancer (3 (6 % vs 16 (17.6 %, р < 0.05 and concomitant diseases. Median CA 125 level in group 1 was 64.96 ng/ml and 180 ng/ml in group 2. Ovarian tumors had solid and cystic structure during US examination in 66 (73 % patients in group 1 and 31 (62 % patients in group 2 had solid ovarian tumors on US examination.Conclusions. The differential diagnostics of primary and metastatic ovarian tumors must include CEA, CA 19–9 and CA 125 serum levels and pelvic US.

  1. The Eag potassium channel as a new prognostic marker in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Schalkwyk Gerhard V

    2010-12-01

    Full Text Available Abstract Background Ovarian cancer is the second most common cancer of the female genital tract in the United Kingdom (UK, accounting for 6% of female deaths due to cancer. This cancer is associated with poor survival and there is a need for new treatments in addition to existing chemotherapy to improve survival. Potassium (K+ channels have been shown to be overexpressed in various cancers where they appear to play a role in cell proliferation and progression. Objectives To determine the expression of the potassium channels Eag and HERG in ovarian cancer tissue and to assess their role in cell proliferation. Methods The expression of Eag and HERG potassium channels was examined in an ovarian cancer tissue microarray. Their role in cell proliferation was investigated by blocking voltage-gated potassium channels in an ovarian cancer cell line (SK-OV-3. Results We show for the first time that high expression of Eag channels in ovarian cancer patients is significantly associated with poor survival (P = 0.016 unlike HERG channel expression where there was no correlation with survival. There was also a significant association of Eag staining with high tumour grade (P = 0.014 and presence of residual disease (P = 0.011. Proliferation of SK-OV-3 cells was significantly (P + channel blockers. Conclusion This novel finding demonstrates a role for Eag as a prognostic marker for survival in patients with ovarian cancer.

  2. Potent cytotoxic effects of Calomeria amaranthoides on ovarian cancers

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    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

  3. New insights in the pathophysiology of ovarian cancer and implications for screening and prevention.

    Science.gov (United States)

    Nezhat, Farr R; Apostol, Radu; Nezhat, Camran; Pejovic, Tanja

    2015-09-01

    Despite advances in medicine, ovarian cancer remains the deadliest of the gynecological malignancies. Herein we present the latest information on the pathophysiology of ovarian cancer and its significance for ovarian cancer screening and prevention. A new paradigm for ovarian cancer pathogenesis presupposes 2 distinct types of ovarian epithelial carcinoma with distinct molecular profiles: type I and type II carcinomas. Type I tumors include endometrioid, clear-cell carcinoma, and low-grade serous carcinoma and mostly arise via defined sequence either from endometriosis or from borderline serous tumors, mostly presenting in an early stage. More frequent type II carcinomas are usually high-grade serous tumors, and recent evidence suggests that the majority arise from the fimbriated end of the fallopian tube. Subsequently, high-grade serous carcinomas usually present at advanced stages, likely as a consequence of the rapid peritoneal seeding from the open ends of the fallopian tubes. On the other hand, careful clinical evaluation should be performed along with risk stratification and targeted treatment of women with premalignant conditions leading to type I cancers, most notably endometriosis and endometriomas. Although the chance of malignant transformation is low, an understanding of this link offers a possibility of prevention and early intervention. This new evidence explains difficulties in ovarian cancer screening and helps in forming new recommendations for ovarian cancer risk evaluation and prophylactic treatments.

  4. Expression and roles of Slit/Robo in human ovarian cancer.

    Science.gov (United States)

    Dai, Cai Feng; Jiang, Yi Zhou; Li, Yan; Wang, Kai; Liu, Pei Shu; Patankar, Manish S; Zheng, Jing

    2011-05-01

    The Slit glycoproteins and their Roundabout (Robo) receptors regulate migration and growth of many types of cells including human cancer cells. However, little is known about the expression and roles of Slit/Robo in human ovarian cancer. Herein, we examined the expression of Slit/Robo in human normal and malignant ovarian tissues and its potential participation in regulating migration and proliferation of human ovarian cancer cells using two ovarian cancer cell lines, OVCAR-3 and SKOV-3. We demonstrated that Slit2/3 and Robo1 were immunolocalized primarily in stromal cells in human normal ovaries and in cancer cells in many histotypes of ovarian cancer tissues. Protein expression of Slit2/3 and Robo1/4 was also identified in OVCAR-3 and SKOV-3 cells. However, recombinant human Slit2 did not significantly affect SKOV-3 cell migration, and OVCAR-3 and SKOV-3 cell proliferation. Slit2 also did not induce ERK1/2 and AKT1 phosphorylation in OVCAR-3 and SKOV-3 cells. The current findings indicate that three major members (Slit2/3 and Robo1) of Slit/Robo family are widely expressed in the human normal and malignant ovarian tissues and in OVCAR-3 and SKOV-3 cells. However, Slit/Robo signaling may not play an important role in regulating human ovarian cancer cell proliferation and migration.

  5. An update on the role of PET/CT and PET/MRI in ovarian cancer

    Energy Technology Data Exchange (ETDEWEB)

    Khiewvan, Benjapa [Hospital of the University of Pennsylvania, Department of Radiology, Philadelphia, PA (United States); Mahidol University, Division of Nuclear Medicine, Department of Radiology, Faculty of Medicine Siriraj Hospital, Bangkok (Thailand); Torigian, Drew A.; Emamzadehfard, Sahra; Paydary, Koosha; Salavati, Ali; Houshmand, Sina; Werner, Thomas J.; Alavi, Abass [Hospital of the University of Pennsylvania, Department of Radiology, Philadelphia, PA (United States)

    2017-06-15

    This review article summarizes the role of PET/CT and PET/MRI in ovarian cancer. With regard to the diagnosis of ovarian cancer, the presence of FDG uptake within the ovary of a postmenopausal woman raises the concern for ovarian cancer. Multiple studies show that FDG PET/CT can detect lymph node and distant metastasis in ovarian cancer with high accuracy and may, therefore, alter the management to obtain better clinical outcomes. Although PET/CT staging is superior for N and M staging of ovarian cancer, its role is limited for T staging. Additionally, FDG PET/CT is of great benefit in evaluating treatment response and has prognostic value in patients with ovarian cancer. FDG PET/CT also has value to detect recurrent disease, particularly in patients with elevated serum CA-125 levels and negative or inconclusive conventional imaging test results. PET/MRI may beneficial for tumor staging because MRI has higher soft tissue contrast and no ionizing radiation exposure compared to CT. Some non-FDG PET radiotracers such as {sup 18}F-fluorothymidine (FLT) or {sup 11}C-methionine (MET) have been studied in preclinical and clinical studies as well and may play a role in the evaluation of patients with ovarian cancer. (orig.)

  6. Upregulated microRNA-224 promotes ovarian cancer cell proliferation by targeting KLLN.

    Science.gov (United States)

    Hu, Ke; Liang, Meng

    2017-02-01

    Human epithelial ovarian cancer is a complex disease, with low 5-yr survival rate largely due to the terminal stage at diagnosis in most patients. MicroRNAs play critical roles during epithelial ovarian cancer progression in vivo and have also been shown to regulate characteristic of ovarian cancer cell line in vitro. Alterative microRNA-224 (microRNA-224) expression affects human epithelial ovarian cancer cell survival, apoptosis, and metastasis. However, people know little about the effects of microRNA-224 on epithelial ovarian cancer cell proliferation. In the current study, we found that the microRNA-224 expression level of human syngeneic epithelial ovarian cancer cells HO8910 (low metastatic ability) was lower than that of HO8910PM (high metastatic ability). Furthermore, microRNA-224 was confirmed to target KLLN in HO8910 and HO8910PM. The known KLLN downstream target cyclin A was regulated by microRNA-224 in HO8910 and HO8910PM. In addition, overexpression of microRNA-224 enhanced the proliferation abilities of HO8910 and knockdown of microRNA-224 suppressed the proliferation abilities of HO8910PM by KLLN-cyclin A pathway. Our results provide new data about microRNAs and their targets involved in proliferation of epithelial ovarian cancer cells by modulating the downstream signaling.

  7. TALEN-mediated somatic mutagenesis in murine models of cancer.

    Science.gov (United States)

    Zhang, Shuyuan; Li, Lin; Kendrick, Sara L; Gerard, Robert D; Zhu, Hao

    2014-09-15

    Cancer genome sequencing has identified numerous somatic mutations whose biologic relevance is uncertain. In this study, we used genome-editing tools to create and analyze targeted somatic mutations in murine models of liver cancer. Transcription activator-like effector nucleases (TALEN) were designed against β-catenin (Ctnnb1) and adenomatous polyposis coli (Apc), two commonly mutated genes in hepatocellular carcinoma (HCC), to generate isogenic HCC cell lines. Both mutant cell lines exhibited evidence of Wnt pathway dysregulation. We asked whether these TALENs could create targeted somatic mutations after hydrodynamic transfection into mouse liver. TALENs targeting β-catenin promoted endogenous HCC carrying the intended gain-of-function mutations. However, TALENs targeting Apc were not as efficient in inducing in vivo homozygous loss-of-function mutations. We hypothesized that hepatocyte polyploidy might be protective against TALEN-induced loss of heterozygosity, and indeed Apc gene editing was less efficient in tetraploid than in diploid hepatocytes. To increase efficiency, we administered adenoviral Apc TALENs and found that we could achieve a higher mutagenesis rate in vivo. Our results demonstrate that genome-editing tools can enable the in vivo study of cancer genes and faithfully recapitulate the mosaic nature of mutagenesis in mouse cancer models. Cancer Res; 74(18); 5311-21. ©2014 AACR.

  8. Clodronate inhibits tumor angiogenesis in mouse models of ovarian cancer

    Science.gov (United States)

    Reusser, Nicole M; Dalton, Heather J; Pradeep, Sunila; Gonzalez-Villasana, Vianey; Jennings, Nicholas B; Vasquez, Hernan G; Wen, Yunfei; Rupaimoole, Rajesh; Nagaraja, Archana S; Gharpure, Kshipra; Miyake, Takahito; Huang, Jie; Hu, Wei; Lopez-Berestein, Gabriel; Sood, Anil K

    2014-01-01

    Purpose Bisphosphonates have been shown to inhibit and deplete macrophages. The effects of bisphosphonates on other cell types in the tumor microenvironment have been insufficiently studied. Here, we sought to determine the effects of bisphosphonates on ovarian cancer angiogenesis and growth via their effect on the microenvironment, including macrophage, endothelial and tumor cell populations. Experimental Design Using in vitro and in vivo models, we examined the effects of clodronate on angiogenesis and macrophage density, and the overall effect of clodronate on tumor size and metastasis. Results Clodronate inhibited the secretion of pro-angiogenic cytokines by endothelial cells and macrophages, and decreased endothelial migration and capillary tube formation. In treated mice, clodronate significantly decreased tumor size, number of tumor nodules, number of tumor-associated macrophages and tumor capillary density. Conclusions Clodronate is a potent inhibitor of tumor angiogenesis. These results highlight clodronate as a potential therapeutic for cancer. PMID:24841852

  9. Chronic Recreational Physical Inactivity and Epithelial Ovarian Cancer Risk

    DEFF Research Database (Denmark)

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

    2016-01-01

    recreational physical activity were classified as inactive, according to the 2008 Physical Activity Guidelines for Americans. The association between physical inactivity exposure and EOC risk overall was assessed using multivariable logistic regression. Subgroup analysis was performed based upon EOC histotype......It is estimated that 5% of women in the United States and 10% to 50% of women worldwide are physically inactive. Previous studies have demonstrated that recreational physical activity is associated with decreased risks of developing breast, colon, and endometrial cancers. The association between...... physical activity and epithelial ovarian cancer (EOC) is less clear. Despite extensive research, including several epidemiological studies and 2 systematic reviews, insufficient and inconsistent evidence is available to support an independent association between recreational physical activity and risk...

  10. 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.

  11. Role of CXCL12 in metastasis of human ovarian cancer

    Institute of Scientific and Technical Information of China (English)

    JIANG Yu-ping; WU Xiao-hua; XING Han-ying; DU Xing-yan

    2007-01-01

    Background In a previous study, we have verified that CXCR4 expression is correlated with tumor aggressive progression and poor prognosis in patients with epithelial ovarian cancer. The aim of this study was to explore the effect of CXCL12-CXCR4 axis on the metastasis of human ovarian cancer.Methods The expressions of CXCR4 and CXCL12 mRNA and protein in human ovarian cancer cell line CAOV-3 was detected by RT-PCR and immunocytochemistry. Methythiazolyltetrazolium (MTT) was used to analyze the effect of different concentrations of CXCL12 on the proliferation of CAOV-3 cells. Transwell invasion chamber and matrigel were used to evaluate the effect of various concentrations of CXCL12 and ascites on the migration and invasion of CAOV-3 cells. The expressions of integrin β1 and vascular endothelial growth factor-C (VEGF-C) mRNA were detected by RT-PCR. Data were analyzed using ANOVA by SAS 6.12.Results Under serum-free suboptimal culture conditions, CXCL12 (100 ng/ml) significantly enhanced the proliferation of CAOV-3 cells compared with the control and 10 ng/ml CXCL12 groups (0.428±0.051 vs. 0.325±0.045 and 0.328±0.039, P<0.05). This enhancing effect of CXCL12 was significantly inhibited by 10 μg/ml neutralizing CXCR4 antibody or 1 μg/ml CXCR4 antagonist AMD3100. However, 10 μg/ml neutralizing CXCR4 antibody could not inhibit cell proliferation without CXCL12. The levels of migration and invasion of the CAOV-3 cells treated with 100 ng/ml CXCL12 were significantly higher than those in the control (migration: 523.3±25.2 vs 108.0±7.2; invasion: 39.3±4.0 vs. 4.0±1.0). The enhancing effect of CXCL12 on cell migration and invasion increased with the concentration of CXCL12 (100 ng/ml vs10 ng/ml: migration, 523.3±25.2 vs 211.7±24.7; invasion, 39.3±4.0 vs 15.7±3.1, P<0.05), and was strongly inhibited by 10 μg/ml neutralizing CXCR4 antibody or 1 μg/ml AMD3100. The number of migrated and invading cells in the CAOV-3 added with ascites was significantly

  12. Low Programmed Cell Death 5 Expression is a Prognostic Factor in Ovarian Cancer

    Institute of Scientific and Technical Information of China (English)

    Li Gao; Xue Ye; Rui-Qiong Ma; Hong-Yan Cheng; Hong-Jing Han; Heng Cui; Li-Hui Wei

    2015-01-01

    Background:Ovarian cancer is a leading gynecological malignancy.We investigated the prognostic value of programmed cell death 5 (PDCD5) in patients with ovarian cancer.Methods:Expression levels ofPDCD5 mRNA and protein were examined in six ovarian cancer cell lines (SKOV3,CAOV3,ES2,OV1,3AO,and HOC1A) and one normal ovarian epithelial cell line (T29) using reverse transcription polymerase chain reaction,Westem blotting,and flow cytometry.After inducing PDCD5 induction in SKOV3 cells or treating this cell line with taxol or doxorubicin (either alone or combined),apoptosis was measured by Annexin V-FITC/propidium iodide staining.Correlations between PDCD5 protein expression and pathological features,histological grade,FIGO stage,effective cytoreductive surgery,and serum cancer antigen-125 values were evaluated in patients with ovarian cancer.Results:PDCD5 mRNA and protein expression were downregulated in ovarian cancer cells.Recombinant human PDCD5 increased doxorubicin-induced apoptosis in SKOV3 cells (15.96 ± 2.07%,vs.3.17 ± 1.45% in controls).In patients with ovarian cancer,PDCD5 expression was inversely correlated with FIGO stage,pathological grade,and patient survival (P < 0.05,R =0.7139 for survival).Conclusions:PDCD5 expression is negatively correlated with disease progression and stage in ovarian cancer.Therefore,measuring PDCD5 expression may be a good method of determining the prognosis of ovarian cancer patients.

  13. 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.

  14. [Magnetic resonance imaging (MRI) in the diagnosis of recurrences of ovarian cancer in the small pelvis].

    Science.gov (United States)

    Bulanova, I M; Bulanova, T V; Burenchev, D V

    2005-01-01

    The paper provides the results of small pelvic magnetic resonance tomography (MRI) in 62 patients with ovarian cancer after primary special treatment. Out of them 50 patients were found to have recurrences and metastases of the underlying disease, 12 patients had clinical remission. The study yielded MR signs and MR semiotics of recurrences of ovarian cancer in the small pelvis. The capacities of MRI with low and high intensities of a magnetic field were comparatively studied in the diagnosis of recurrences and metastases of ovarian cancer.

  15. Orlistat, a novel potent antitumor agent for ovarian cancer: proteomic analysis of ovarian cancer cells treated with Orlistat.

    Science.gov (United States)

    Huang, Hui-Qiong; Tang, Jing; Zhou, Sheng-Tao; Yi, Tao; Peng, Hong-Ling; Shen, Guo-Bo; Xie, Na; Huang, Kai; Yang, Tao; Wu, Jin-Hua; Huang, Can-Hua; Wei, Yu-Quan; Zhao, Xia

    2012-08-01

    Orlistat is an orally administered anti-obesity drug that has shown significant antitumor activity in a variety of tumor cells. To identify the proteins involved in its antitumor activity, we employed a proteomic approach to reveal protein expression changes in the human ovarian cancer cell line SKOV3, following Orlistat treatment. Protein expression profiles were analyzed by 2-dimensional polyacrylamide gel electrophoresis (2-DE) and protein identification was performed on a MALDI-Q-TOF MS/MS instrument. More than 110 differentially expressed proteins were visualized by 2-DE and Coomassie brilliant blue staining. Furthermore, 71 proteins differentially expressed proteins were positively identified via mass spectrometry (MS)/MS analysis. In particular, PKM1/2, a key enzyme involved in tumorigenesis, was found to be significantly downregulated in SKOV3 cells following treatment with Orlistat. Moreover, PKM1/2 was proved to be downregulated in SKOV3 cells by western blot analysis after treatment with Orlistat. Taken together, using proteomic tools, we identified several differentially expressed proteins that underwent Orlistat-induced apoptosis, particularly PKM2. These changes confirmed our hypothesis that Orlistat is a potential inhibitor of ovarian cancer and can be used as a novel adjuvant antitumor agent.

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

    NARCIS (Netherlands)

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

    2014-01-01

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

  17. The origin of serous ovarian cancer may be found in the uterus: a novel hypothesis.

    NARCIS (Netherlands)

    Massuger, L.F.A.G.; Roelofsen, T.; Ham, M. van der; Bulten, J.

    2010-01-01

    Since 1971 the incessant ovulation theory by Fathalla is widely accepted as theory for ovarian carcinogenesis, supported mainly by epidemiological findings. However, this theory cannot explain the protective effect of hysterectomy and tubal ligation on the incidence of ovarian cancer. Furthermore, n

  18. The origin of serous ovarian cancer may be found in the uterus: a novel hypothesis.

    NARCIS (Netherlands)

    Massuger, L.F.A.G.; Roelofsen, T.; Ham, M. van der; Bulten, J.

    2010-01-01

    Since 1971 the incessant ovulation theory by Fathalla is widely accepted as theory for ovarian carcinogenesis, supported mainly by epidemiological findings. However, this theory cannot explain the protective effect of hysterectomy and tubal ligation on the incidence of ovarian cancer. Furthermore,

  19. The origin of serous ovarian cancer may be found in the uterus: a novel hypothesis.

    NARCIS (Netherlands)

    Massuger, L.F.A.G.; Roelofsen, T.; Ham, M. van der; Bulten, J.

    2010-01-01

    Since 1971 the incessant ovulation theory by Fathalla is widely accepted as theory for ovarian carcinogenesis, supported mainly by epidemiological findings. However, this theory cannot explain the protective effect of hysterectomy and tubal ligation on the incidence of ovarian cancer. Furthermore, n

  20. 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