WorldWideScience

Sample records for spontaneous ovarian cancer

  1. Characterization of the Chicken Ovarian Cancer Model

    National Research Council Canada - National Science Library

    Rodriquez, Gustavo

    2001-01-01

    .... Unlike other ovarian cancer models, which require experimental induction of ovarian tumors, chickens develop ovarian adenocarcinoma spontaneously, with an incidence ranging from 13 to 40 percent...

  2. Characterization of the Chicken Ovarian Cancer Model

    National Research Council Canada - National Science Library

    Rodriguez, Gustavo C

    2004-01-01

    .... Unlike other ovarian cancer models, which require experimental induction of ovarian tumors, chickens develop ovarian adenocarcinoma spontaneously, with an incidence ranging from 13 to 40 percent...

  3. Characterization of the Chicken Ovarian Cancer Model

    National Research Council Canada - National Science Library

    Rodriguez, Gustavo

    2002-01-01

    .... Unlike other ovarian cancer models, which require experimental induction of ovarian tumors, chickens develop ovarian adenocarcinoma spontaneously, with an incidence ranging from 13 to 40 percent...

  4. Characterization of the Chicken Ovarian Cancer Model

    National Research Council Canada - National Science Library

    Rodriguez, Gustavo C

    2005-01-01

    .... Unlike other ovarian cancer models, which require experimental induction of ovarian tumors, chickens develop ovarian adenocarcinoma spontaneously, with an incidence ranging from 13 to 40 percent...

  5. Characterization of the Chicken Ovarian Cancer Model

    National Research Council Canada - National Science Library

    Rodriguez, Gustavo

    2003-01-01

    .... Unlike other ovarian cancer models, which require experimental induction of ovarian tumors, chickens develop ovarian adenocarcinoma spontaneously, with an incidence ranging from 13 to 40 percent...

  6. Ovarian Cancer

    Science.gov (United States)

    ... I find more information about ovarian and other gynecologic cancers? Centers for Disease Control and Prevention: 800-CDC-INFO or www. cdc. gov/ cancer/ gynecologic National Cancer Institute: 800-4-CANCER or www. ...

  7. Ovarian Cancer

    Science.gov (United States)

    ... contraceptives may have a reduced risk of ovarian cancer. But oral contraceptives do have risks, so discuss whether the benefits outweigh those risks based on your situation. Discuss your risk factors ... of breast and ovarian cancers, bring this up with your doctor. Your doctor ...

  8. Ovarian cancer

    International Nuclear Information System (INIS)

    Wakabayashi, Yukari; Yachida, Meri; Akata, Soichi; Kawana, Koji; Kotake, Fumio; Kakizaki, Dai; Abe, Kimihiko; Negishi, Noriyuki; Akiya, Kiyoshi

    1988-01-01

    In 40 patients undergoing pre-treatment for an ovarian tumor, a CT scan of the pelvis and measurements of their CA 125, CA 19 - 9, IAP (immunosupressive acidic antigen), and TPA (tissue polypeptide antigen were performed. The specificity and sensitivity of the CT diagnosis was found to be better than any of other tumor markers measurements. Comparison of the 4 markers showed that the CA 125 testing had the greatest sensitivity in detecting an ovarian cancer. Moreover, the sensitivity of CA 125, was better than a combination of the 4 markers. Thus, a CT scan still remains necessary for the diagnosis of an ovarian cancer. (author)

  9. VEGFR2-Targeted Ultrasound Imaging Agent Enhances the Detection of Ovarian Tumors at Early Stage in Laying Hens, a Preclinical Model of Spontaneous Ovarian Cancer.

    Science.gov (United States)

    Barua, Animesh; Yellapa, Aparna; Bahr, Janice M; Machado, Sergio A; Bitterman, Pincas; Basu, Sanjib; Sharma, Sameer; Abramowicz, Jacques S

    2015-07-01

    Tumor-associated neoangiogenesis (TAN) is an early event in ovarian cancer (OVCA) development. Increased expression of vascular endothelial growth factor receptor 2 (VEGFR2) by TAN vessels presents a potential target for early detection by ultrasound imaging. The goal of this study was to examine the suitability of VEGFR2-targeted ultrasound contrast agents in detecting spontaneous OVCA in laying hens. Effects of VEGFR2-targeted contrast agents in enhancing the intensity of ultrasound imaging from spontaneous ovarian tumors in hens were examined in a cross-sectional study. Enhancement in the intensity of ultrasound imaging was determined before and after injection of VEGFR2-targeted contrast agents. All ultrasound images were digitally stored and analyzed off-line. Following scanning, ovarian tissues were collected and processed for histology and detection of VEGFR2-expressing microvessels. Enhancement in visualization of ovarian morphology was detected by gray-scale imaging following injection of VEGFR2-targeted contrast agents. Compared with pre-contrast, contrast imaging enhanced the intensities of ultrasound imaging significantly (p ultrasound imaging was significantly (p ultrasound imaging in hens with OVCA were positively correlated with increased (p therapeutics. © The Author(s) 2014.

  10. Interleukin 16- (IL-16-) Targeted Ultrasound Imaging Agent Improves Detection of Ovarian Tumors in Laying Hens, a Preclinical Model of Spontaneous Ovarian Cancer.

    Science.gov (United States)

    Barua, Animesh; Yellapa, Aparna; Bahr, Janice M; Adur, Malavika K; Utterback, Chet W; Bitterman, Pincas; Basu, Sanjib; Sharma, Sameer; Abramowicz, Jacques S

    2015-01-01

    Limited resolution of transvaginal ultrasound (TVUS) scanning is a significant barrier to early detection of ovarian cancer (OVCA). Contrast agents have been suggested to improve the resolution of TVUS scanning. Emerging evidence suggests that expression of interleukin 16 (IL-16) by the tumor epithelium and microvessels increases in association with OVCA development and offers a potential target for early OVCA detection. The goal of this study was to examine the feasibility of IL-16-targeted contrast agents in enhancing the intensity of ultrasound imaging from ovarian tumors in hens, a model of spontaneous OVCA. Contrast agents were developed by conjugating biotinylated anti-IL-16 antibodies with streptavidin coated microbubbles. Enhancement of ultrasound signal intensity was determined before and after injection of contrast agents. Following scanning, ovarian tissues were processed for the detection of IL-16 expressing cells and microvessels. Compared with precontrast, contrast imaging enhanced ultrasound signal intensity significantly in OVCA hens at early (P ultrasound signals in OVCA hens were associated with increased frequencies of IL-16 expressing cells and microvessels. These results suggest that IL-16-targeted contrast agents improve the visualization of ovarian tumors. The laying hen may be a suitable model to test new imaging agents and develop targeted anti-OVCA therapeutics.

  11. Interleukin 16- (IL-16- Targeted Ultrasound Imaging Agent Improves Detection of Ovarian Tumors in Laying Hens, a Preclinical Model of Spontaneous Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Animesh Barua

    2015-01-01

    Full Text Available Limited resolution of transvaginal ultrasound (TVUS scanning is a significant barrier to early detection of ovarian cancer (OVCA. Contrast agents have been suggested to improve the resolution of TVUS scanning. Emerging evidence suggests that expression of interleukin 16 (IL-16 by the tumor epithelium and microvessels increases in association with OVCA development and offers a potential target for early OVCA detection. The goal of this study was to examine the feasibility of IL-16-targeted contrast agents in enhancing the intensity of ultrasound imaging from ovarian tumors in hens, a model of spontaneous OVCA. Contrast agents were developed by conjugating biotinylated anti-IL-16 antibodies with streptavidin coated microbubbles. Enhancement of ultrasound signal intensity was determined before and after injection of contrast agents. Following scanning, ovarian tissues were processed for the detection of IL-16 expressing cells and microvessels. Compared with precontrast, contrast imaging enhanced ultrasound signal intensity significantly in OVCA hens at early (P<0.05 and late stages (P<0.001. Higher intensities of ultrasound signals in OVCA hens were associated with increased frequencies of IL-16 expressing cells and microvessels. These results suggest that IL-16-targeted contrast agents improve the visualization of ovarian tumors. The laying hen may be a suitable model to test new imaging agents and develop targeted anti-OVCA therapeutics.

  12. Spontaneous spheroid budding from monolayers: a potential contribution to ovarian cancer dissemination.

    Science.gov (United States)

    Pease, Jillian C; Brewer, Molly; Tirnauer, Jennifer S

    2012-07-15

    Ovarian cancer is the most lethal gynaecologic cancer, in large part because of its early dissemination and rapid development of chemotherapy resistance. Spheroids are clusters of tumor cells found in the peritoneal fluid of patients that are thought to promote this dissemination. Current models suggest that spheroids form by aggregation of single tumor cells shed from the primary tumor. Here, we demonstrate that spheroids can also form by budding directly as adherent clusters from a monolayer. Formation of budded spheroids correlated with expression of vimentin and lack of cortical E-cadherin. We also found that compared to cells grown in monolayers, cells grown as spheroids acquired progressive resistance to the chemotherapy drugs Paclitaxel and Cisplatin. This resistance could be completely reversed by dissociating the spheroids. Our observations highlight a previously unappreciated mode of spheroid formation that might have implications for tumor dissemination and chemotherapy resistance in patients, and suggest that this resistance might be reversed by spheroid dissociation.

  13. Ovarian Cancer FAQ

    Science.gov (United States)

    ... cancer, ovarian cancer, colon cancer, or endometrial cancer (cancer of the lining of the uterus ) Personal history of breast cancer Mutations in BRCA1 ... If a woman is thought to have ovarian cancer, surgery usually is recommended to remove the uterus, ovaries, and fallopian tubes . Lymph nodes and tissues ...

  14. 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....

  15. Ovarian hyperstimulation syndrome in a spontaneous pregnancy ...

    African Journals Online (AJOL)

    It is known that most cases of Ovarian Hyperstimulation Syndrome (OHSS) are associated with the therapies for ovulation induction. However, OHSS may rarely be associated with a spontaneous ovulatory cycle, usually in the case of multiple gestations, hypothyroidism or polycystic ovary syndrome. We report a case of ...

  16. Dietary supplementation of Ashwagandha (Withania somnifera, Dunal) enhances NK cell function in ovarian tumors in the laying hen model of spontaneous ovarian cancer.

    Science.gov (United States)

    Barua, Animesh; Bradaric, Michael J; Bitterman, Pincas; Abramowicz, Jacques S; Sharma, Sameer; Basu, Sanjib; Lopez, Heather; Bahr, Janice M

    2013-12-01

    Ovarian cancer (OVCA) disseminates in a distinct pattern through peritoneal metastasis and little is known about the immunosuppression in the tumor microenvironment. Our goal was to determine changes in NK cell population during OVCA development and the effects of Ashwagandha (Withania somnifera, Dunal) supplementation on NK cell localization in laying hens with OVCA. Frequency of NK cells in ovarian tumors at early and late stages in 3- to 4-year-old hens (exploratory study) as well as in hens supplemented with dietary Ashwagandha root powder for 90 days (prospective study) was examined. The population of stromal NK cells but not the intratumoral NK cells increased with OVCA development and progression. Ashwagandha supplementation decreased the incidence and progression of OVCA. Both the stromal and intratumoral NK cell population increased significantly (P < 0.0001) in Ashwagandha supplementated hens. The results of this study suggest that the population of stromal and tumorinfiltrating NK cells is increased by dietary Ashwagandha supplementation. Thus, Ashwagandha may enhance antitumor function of NK cells. This study may be useful for a clinical study to determine the effects of dietary Ashwagandha on NK cell immune function in patients with ovarian cancer. © 2013 John Wiley & Sons Ltd.

  17. Multiple metastases from ovarian cancer

    African Journals Online (AJOL)

    Epithelial ovarian cancer is one of the most common ovarian tumours. Ovarian cancer affects women in the age group >60 years much more frequently than younger women. At the time of diagnosis, cancer will already have spread beyond the ovaries in approximately 75% of cases. We report a case of epithelial ovarian ...

  18. 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

  19. Screening for Ovarian Cancer

    Science.gov (United States)

    ... seen, further testing is often needed using surgery. • CA-125 blood test. This test looks for CA-125, a substance that can be found in high ... in women with ovarian cancer. However, a high CA-125 level does not always mean a woman has ...

  20. Intravital Microscopy in Evaluating Patients With Primary Peritoneal, Fallopian Tube, or Stage IA-IV Ovarian Cancer

    Science.gov (United States)

    2017-12-28

    Fallopian Tube Carcinoma; Primary Peritoneal Carcinoma; Stage I Ovarian Cancer; Stage IA Ovarian Cancer; Stage IB Ovarian Cancer; Stage IC Ovarian Cancer; Stage II Ovarian Cancer; Stage IIA Ovarian Cancer; Stage IIB Ovarian Cancer; Stage IIC Ovarian Cancer; Stage III Ovarian Cancer; Stage IIIA Ovarian Cancer; Stage IIIB Ovarian Cancer; Stage IIIC Ovarian Cancer; Stage IV Ovarian Cancer

  1. 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...

  2. CA 125 in ovarian cancer

    NARCIS (Netherlands)

    van der Burg, M. E.; Lammes, F. B.; Verweij, J.

    1992-01-01

    The serum tumour marker CA 125 is useful in the management of ovarian cancer, although it has its limitations. Approximately 85% of the ovarian cancer patients have an increased serum CA 125 at the start of treatment. There is a good correlation between the course of CA 125 and the clinical response

  3. Hormone therapy and ovarian cancer

    DEFF Research Database (Denmark)

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

    2009-01-01

    CONTEXT: Studies have suggested an increased risk of ovarian cancer among women taking postmenopausal hormone therapy. Data are sparse on the differential effects of formulations, regimens, and routes of administration. OBJECTIVE: To assess risk of ovarian cancer in perimenopausal and postmenopau...... therapy each year. CONCLUSION: Regardless of the duration of use, the formulation, estrogen dose, regimen, progestin type, and route of administration, hormone therapy was associated with an increased risk of ovarian cancer.......CONTEXT: Studies have suggested an increased risk of ovarian cancer among women taking postmenopausal hormone therapy. Data are sparse on the differential effects of formulations, regimens, and routes of administration. OBJECTIVE: To assess risk of ovarian cancer in perimenopausal...... and postmenopausal women receiving different hormone therapies. DESIGN AND SETTING: Nationwide prospective cohort study including all Danish women aged 50 through 79 years from 1995 through 2005 through individual linkage to Danish national registers. Redeemed prescription data from the National Register...

  4. Subtypes of Ovarian Cancer and Ovarian Cancer Screening

    Directory of Open Access Journals (Sweden)

    Masafumi Koshiyama

    2017-03-01

    Full Text Available 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.

  5. Subtypes of Ovarian Cancer and Ovarian Cancer Screening.

    Science.gov (United States)

    Koshiyama, Masafumi; Matsumura, Noriomi; Konishi, Ikuo

    2017-03-02

    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.

  6. 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....

  7. [Epidemiological profile of ovarian cancer].

    Science.gov (United States)

    Rivas-Corchado, Luz María; González-Geroniz, Manuel; Hernández-Herrera, Ricardo Jorge

    2011-09-01

    In Mexico, ovarian cancer represents 5.3% of cancer diagnoses in all age groups and 21% of gynecologic cancers. The states with the highest incidence of this disease Nuevo León, Mexico State and Federal District. To determine the epidemiological profile of ovarian cancer. A retrospective cross-sectional study that included all patients with complete records, diagnosed with ovarian cancer treated at the Oncology department UMAE Monterrey No. 23, January 2009 to 31 December 2009. We identified 40 patients with ovarian cancer. The average age of menarche was 12.7 years, 40% were of reproductive age, 25% were nulliparous, 15% had a pregnancy and 37.5% had two pregnancies. Of the total patients, 17% had a history of breast cancer, 40% used a contraceptive method, 37% used oral contraceptives. The tumor marker CA 125 was found in 40% of patients, 63.1% had ultrasound markers for cancer. The most frequent clinical stage 1A in which they found 32% of cases. Papillary serous adenocarcinoma was diagnosed in 25% of patients, endometroid adenocarcinoma and mucinous tumor of low malignant potential was diagnosed borderline at 20%, poorly differentiated adenocarcinoma in 18% tumor granulosa cells in 7% and papillary adenocarcinoma ring cell adenocarcinoma in 5%. In total, 43% of patients received chemotherapy. The majority of cases tenia50 years or more. The background was the most frequent hereditary breast cancer. There were no deaths during the study.

  8. 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.

  9. 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

  10. Spontaneous Ovarian Hyperstimulation Syndrome in a Term Pregnancy

    Directory of Open Access Journals (Sweden)

    Aytekin Tokmak

    2015-09-01

    Full Text Available Spontaneous OHSS in a term pregnancy is extremely rare. The aim of this study is to present a case of spontaneous ovarian hyperstimulation syndrome (OHSS in a term pregnancy. A 29-year-old primigravida woman conceived spontaneously and was observed up until 35 weeks of gestation. During this time the patient had a normal pregnancy with normal ovaries. She applied to the current clinic during the 37th week of gestation with complaints of rapid weight gain, abdominal disturbance, and pain. Ultrasound examination showed large bilateral ovaries with multiple follicles and mild ascites. At 39 weeks of gestation, the ovaries were the same as detected previously, and a caesarean section was performed due to fetal macrosomia. A healthy female foetus weighing 4060 gr was delivered. The enlarged bilateral ovaries containing multiple follicles were drilled with electrocautery. The ovaries returned to a near normal state for two weeks after the birth. There are no reported cases of spontaneous OHSS in late pregnancy in the literature. Ovarian drilling may be useful during caesarean section. [Cukurova Med J 2015; 40(3.000: 623-626

  11. 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...

  12. 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...

  13. LY2109761 enhances cisplatin antitumor activity in ovarian cancer cells.

    Science.gov (United States)

    Gao, Yuxiu; Shan, Ning; Zhao, Cheng; Wang, Yunhai; Xu, Fuliang; Li, Jiacun; Yu, Xiaoqian; Gao, Lifeng; Yi, Zhengjun

    2015-01-01

    Ovarian cancer is among the most lethal of all malignancies in women. While chemotherapy is the preferred treatment modality, chemoresistance severely limits treatment success. Because transforming growth factor-beta (TGF-β) could increase survival of ovarian cancer cells in the presence of cisplatin, we conducted a preclinical study of the antitumor effects of the TGF-β type I (TβRI) and type II (TβRII) kinase inhibitor LY2109761 in combination with cisplatin. SKOV3, OV-90 and SKOV3(DDP) cells were treated with LY2109761, and/or cisplatin, and cell viability, apoptosis mRNA and protein expression levels were then evaluated. Furthermore, the efficacy of LY2109761 combined with cisplatin was further examined in established xenograft models. LY2109761 was sufficient to induce spontaneous apoptosis of ovarian cancer cells. Combination with LY2109761 significantly augmented the cytotoxicity of cisplatin in both parental and cisplatin resistant ovarian cancer cells. LY2109761 significantly increased apoptotic cell death in cisplatin-resistant cells. Combination treatment of LY2109761 and cisplatin showed antiproliferative effects and induced a greater rate of apoptosis than the sum of the single-treatment rates and promoted tumor regression in established parental and cisplatin resistant ovarian cancer xenograft models. Chemotherapeutic approaches using LY2109761 might enhance the treatment benefit of the cisplatin in the treatment of ovarian cancer patients.

  14. Ovarian Cancer Pathogenesis: A Model in Evolution

    Directory of Open Access Journals (Sweden)

    Alison M. Karst

    2010-01-01

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

  15. Ovarian and tubal cancer in Denmark

    DEFF Research Database (Denmark)

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

    2016-01-01

    of serous tumors was fairly steady, whereas that of other and unspecified epithelial tumors decreased significantly by 6.4% per year. The incidence of tubal cancer was quite stable. In Norway and Finland, the incidence rates of ovarian and tubal cancer combined decreased from 1993 to 2013 in women aged ...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...... age-standardized (world standard population) incidence rates for overall and subtype-specific ovarian cancer, and for tubal cancer. We compared age-standardized incidence rates, and 1- and 5-year age-standardized relative survival rates, respectively, for ovarian and tubal cancer combined in four...

  16. 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...

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

    Science.gov (United States)

    2014-12-18

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

  18. Fifth Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup (GCIG): clinical trial design for rare ovarian tumours

    NARCIS (Netherlands)

    Leary, A. F.; Quinn, M.; Fujiwara, K.; Coleman, R. L.; Kohn, E.; Sugiyama, T.; Glasspool, R.; Ray-Coquard, I.; Colombo, N.; Bacon, M.; Zeimet, A.; Westermann, A.; Gomez-Garcia, E.; Provencher, D.; Welch, S.; Small, W.; Millan, D.; Okamoto, A.; Stuart, G.; Ochiai, K.

    2017-01-01

    This manuscript reports the consensus statements on designing clinical trials in rare ovarian tumours reached at the fifth Ovarian Cancer Consensus Conference (OCCC) held in Tokyo, November 2015. Three important questions were identified concerning rare ovarian tumours (rare epithelial ovarian

  19. Spontaneous regression of colon cancer.

    Science.gov (United States)

    Kihara, Kyoichi; Fujita, Shin; Ohshiro, Taihei; Yamamoto, Seiichiro; Sekine, Shigeki

    2015-01-01

    A case of spontaneous regression of transverse colon cancer is reported. A 64-year-old man was diagnosed as having cancer of the transverse colon at a local hospital. Initial and second colonoscopy examinations revealed a typical cancer of the transverse colon, which was diagnosed as moderately differentiated adenocarcinoma. The patient underwent right hemicolectomy 6 weeks after the initial colonoscopy. The resected specimen showed only a scar at the tumor site, and no cancerous tissue was proven histologically. The patient is alive with no evidence of recurrence 1 year after surgery. Although an antitumor immune response is the most likely explanation, the exact nature of the phenomenon was unclear. We describe this rare case and review the literature pertaining to spontaneous regression of colorectal cancer. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  20. Ovarian Cancer Prevention Program

    Science.gov (United States)

    1999-10-01

    cancer . JAMA, 277: 997-1003, 1997. 21. Klijn, J.G.M. Should prophylactic surgery be used in women with a high risk of breast cancer ? Eur J Cancer , 33...1996. Decision Making about Prophylactic Oophorectomy 20 35. Lerman, C, and Croyle, R.T. Genetic testing for cancer predisposition : Behavioral science...Daly, M., Masny, A., and Balshem, A. Attitudes about genetic testing for breast - Decision Making about Prophylactic Oophorectomy 24

  1. 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.......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 cancer...... (HBOC) syndrome and the hereditary non-polyposis colorectal cancer (HNPCC) syndrome. Genome-wide array comparative genomic hybridization was applied to 12 HBOC associated tumors with BRCA1 mutations and 8 HNPCC associated tumors with mismatch repair gene mutations with 24 sporadic ovarian cancers...

  2. Lead, selenium and nickel concentrations in epithelial ovarian cancer, borderline ovarian tumor and healthy ovarian tissues.

    Science.gov (United States)

    Canaz, Emel; Kilinc, Metin; Sayar, Hamide; Kiran, Gurkan; Ozyurek, Eser

    2017-09-01

    Wide variation exists in ovarian cancer incidence rates suggesting the importance of environmental factors. Due to increasing environmental pollution, trace elements and heavy metals have drawn attention in studies defining the etiology of cancer, but scant data is available for ovarian cancer. Our aim was to compare the tissue concentrations of lead, selenium and nickel in epithelial ovarian cancer, borderline tumor and healthy ovarian tissues. The levels of lead, selenium and nickel were estimated using atomic absorption spectrophotometry in formalin-fixed paraffin-embedded tissue samples. Tests were carried out in 20 malignant epithelial ovarian cancer, 15 epithelial borderline tumor and 20 non-neoplastic healthy ovaries. Two samples were collected for borderline tumors, one from papillary projection and one from the smooth surface of cyst wall. Pb and Ni concentrations were found to be higher both in malignant and borderline tissues than those in healthy ovaries. Concentrations of Pb and Ni in malignant tissues, borderline papillary projections and capsular tissue samples were not different. Comparison of Se concentrations of malignant, borderline and healthy ovarian tissues did not reveal statistical difference. Studied metal levels were not found to be different in either papillary projection or in cyst wall of the borderline tumors. This study revealed the accumulation of lead and nickel in ovarian tissue is associated with borderline and malignant proliferation of the surface epithelium. Accumulation of these metals in epithelial ovarian cancer and borderline ovarian tumor has not been demonstrated before. Copyright © 2017 Elsevier GmbH. All rights reserved.

  3. National Ovarian Cancer Coalition

    Science.gov (United States)

    ... History Day – Prepare for a Family Conversation About Genetics and Cancer November 08, 2017 Live Webinar on ... us here . Thanksgiving Day, November 23rd, is National Family ... Read ... Tree Display November 19, 2017 @ 10:00AM Hosted by ...

  4. Ovarian cancer mortality and industrial pollution

    International Nuclear Information System (INIS)

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

    2015-01-01

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

  5. Pathogenesis of ovarian cancer: current perspectives | Chesang ...

    African Journals Online (AJOL)

    Objective: To present a review of current knowledge of the pathogenesis of ovarian cancer and its clinical implications. Data Source: Extensive literature search was conducted to identify relevant studies. Study Selection: Studies in the English language about or related to pathogenesis of ovarian cancer were selected.

  6. 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....

  7. 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...

  8. Predictive and therapeutic markers in ovarian cancer

    Science.gov (United States)

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

    2013-03-26

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

  9. Chemoprevention of Ovarian Cancer

    Science.gov (United States)

    2006-10-01

    1Department of Veterinary Sciences Science Park and 2Department of Gyneco- logic Oncology, The University of Texas M. D. Anderson Cancer Center, Houston...breeding colony at the Department of Veterinary Sciences , (Bastrop, Tex.) due to their viral status, reproductive history, or social incompatibili...the Department of Veterinary Sciences campus, an approved facility of the Association for the Assessment and Accreditation of Labo- ratory Animal

  10. Increased risk for ovarian cancer and borderline ovarian tumours in subfertile women with endometriosis

    NARCIS (Netherlands)

    Buis, C. C. M.; van Leeuwen, F. E.; Mooij, T. M.; Burger, C. W.; Lambalk, Cornelis B.; Kortman, Marian; Laven, Joop S. E.; Jansen, Cees A. M.; Helmerhorst, Frans M.; Cohlen, Ben J.; Willemsen, Wim N. P.; Smeenk, Jesper M. J.; Simons, Arnold H. M.; van der Veen, Fulco; Evers, Johannes L. H.; van Dop, Peter A.; Macklon, Nicholas S.

    2013-01-01

    Is ovarian or extra-ovarian endometriosis associated with an increased risk of ovarian cancer and borderline ovarian tumours (BOT)? We found a 3- to 8-fold increased risk of ovarian tumours associated with endometriosis: the magnitude of the risk increase depended on the definition of endometriosis.

  11. Hormone therapy and different ovarian cancers

    DEFF Research Database (Denmark)

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

    2012-01-01

    Postmenopausal hormone therapy use increases the risk of ovarian cancer. In the present study, the authors examined the risks of different histologic types of ovarian cancer associated with hormone therapy. Using Danish national registers, the authors identified 909,946 women who were followed from.......8). Similar increased risks of serous and endometrioid tumors were found with estrogen/progestin therapy, whereas no association was found with mucinous tumors. Consistent with results from recent cohort studies, the authors found that ovarian cancer risk varied according to tumor histology. The types...... 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...

  12. MRI for discriminating metastatic ovarian tumors from primary epithelial ovarian cancers

    OpenAIRE

    Xu, Yanhong; Yang, Jia; Zhang, Zaixian; Zhang, Guixiang

    2015-01-01

    Aims To find specific magnetic resonance imaging (MRI) features to differentiate metastatic ovarian tumors from primary epithelial ovarian cancers. Methods Eleven cases with metastatic ovarian tumors and 26 cases with primary malignant epithelial ovarian cancers were retrospectively studied. All features such as patient characteristics, MRI findings and biomarkers were evaluated. The differences including laterality, configuration, uniformity of locules, diffusion weighted imaging (DWI) signa...

  13. 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....

  14. Functional Proteomics-Based Ovarian Cancer Biomarkers

    Science.gov (United States)

    2010-11-01

    Dupont, Jakob , et al. "Early detection and prognosis of ovarian cancer using serum YKL- 40." Journal of clinical oncology 22.16 (2004): 3330-3339. 41...Survival in Epithelial Ovarian Tumors." The American journal of pathology 154.1 (1999): 119-125. 114  Nielsen , Jens Steen, et al. "Prognostic

  15. Ovarian cancer in an interdisciplinary context

    DEFF Research Database (Denmark)

    Seibæk, Lene

    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.  ......  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...

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

    International Nuclear Information System (INIS)

    Furuya, Mitsuko

    2012-01-01

    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

  17. 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.

  18. Spontaneous rupture of ovarian cystadenocarcinoma: pre- and post-rupture computed tomography evaluation

    Directory of Open Access Journals (Sweden)

    Priscila Silveira Salvadori

    2015-10-01

    Full Text Available AbstractEpithelial ovarian tumors are the most common malignant ovarian neoplasms and, in most cases, eventual rupture of such tumors is associated with a surgical procedure. The authors report the case of a 54-year-old woman who presented with spontaneous rupture of ovarian cystadenocarcinoma documented by computed tomography, both before and after the event. In such cases, a post-rupture staging tends to be less favorable, compromising the prognosis.

  19. Spontaneous rupture of ovarian cystadenocarcinoma: pre- and post-rupture computed tomography evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Salvadori, Priscila Silveira; Atzingen, Augusto Castelli von; D' Ippolito, Giuseppe [Universidade Federal de Sao Paulo (EPM/UNIFESP), Sao Paulo, SP (Brazil). Escola Paulista de Medicina; Bomfim, Lucas Novais [Universidade Tiradentes (UNIT), Maceio, AL, (Brazil)

    2015-09-15

    Epithelial ovarian tumors are the most common malignant ovarian neoplasms and, in most cases, eventual rupture of such tumors is associated with a surgical procedure. The authors report the case of a 54-year-old woman who presented with spontaneous rupture of ovarian cystadenocarcinoma documented by computed tomography, both before and after the event. In such cases, a post-rupture staging tends to be less favorable, compromising the prognosis. (author)

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

    DEFF Research Database (Denmark)

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

    2009-01-01

    OBJECTIVE: To validate the data on epithelial ovarian cancer, fallopian tube cancer and borderline ovarian tumors registered in the nationwide Danish Gynecological Cancer Database (DGCD) in 2005 and 2006. The DGCD is a multidisciplinary database that contains data for research and quality...... improvement. DESIGN: Comparative registry-based study supplemented with data from medical records. SETTING: Six hospitals in Denmark. PARTICIPANTS: Women registered with epithelial ovarian cancer, fallopian tube cancer and borderline ovarian tumor. MAIN OUTCOME MEASURE: Data completeness and strength......: The validity of ovarian cancer data in the DGCD is sufficient for quality monitoring in gynecological oncology Udgivelsesdato: 2009...

  1. High CA-125 and CA19-9 levels in spontaneous ruptured ovarian endometriomas.

    Science.gov (United States)

    Dai, Xinyue; Jin, Chu; Hu, Yan; Zhang, Qian; Yan, Xiaojian; Zhu, Fangfang; Lin, Feng

    2015-10-23

    To evaluate the clinical significance of serum CA-125 and CA19-9 in women with spontaneous ruptured ovarian endometriomas. From January 2006 to April 2015, a total of 1653 women were diagnosed with ovarian endometriomas, and 43 women were diagnosed with the spontaneous rupture of their ovarian endometrioma. In addition, 70 women diagnosed with unruptured ovarian endometriomas were chosen to serve as control subjects. Serum CA-125 and CA19-9 levels, together with the clinical materials, were collected. Serum CA-125, CA19-9, and the combined biomarkers were shown to be obviously elevated in the spontaneous ruptured ovarian endometrioma group (p=0.001, p=0.001, p=0.001, respectively). The AUC value for the combined biomarkers was 0.992 (95% CI, 0.981-1.000), with a high sensitivity and specificity of nearly 100% and 93.6%, respectively. Moreover, the maximum diameter of the mass was significantly (p=0.001) increased in the ruptured group. Serum CA-125 and CA19-9 were significantly increased in patients with spontaneous ruptured ovarian endometriomas. Moreover, the combined biomarkers were better than either CA-125 or CA19-9 alone in the diagnosis of a spontaneous rupture of the ovarian endometrioma. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Ovarian hyperstimulation syndrome in a spontaneous singleton pregnancy.

    Science.gov (United States)

    Cabar, Fábio Roberto

    2016-05-24

    The ovarian hyperstimulation syndrome is the combination of increased ovarian volume, due to the presence of multiple cysts and vascular hyperpermeability, with subsequent hypovolemia and hemoconcentration. We report a case of spontaneous syndrome in a singleton pregnancy. This was a spontaneous pregnancy with 12 weeks of gestational age. The pregnancy was uneventful until 11 weeks of gestational age. After that, the pregnant woman complained of progressive abdominal distention associated with abdominal discomfort. She did not report other symptoms. In the first trimester, a routine ultrasonography showed enlarged ovaries, multiples cysts and ascites. Upon admission, the patient was hemodynamically stable, her serum β-hCG was 24,487mIU/mL, thyroid-stimulating hormone was 2.2µUI/mL and free T4 was 1.8ng/dL. All results were within normal parameters. However, levels of estradiol were high (10,562pg/mL). During hospitalization, she received albumin, furosemide and prophylactic dose of enoxaparin. The patient was discharged on the sixth hospital day. RESUMO A síndrome de hiperestimulação ovariana é a combinação do aumento dos ovários, devido à presença de múltiplos cistos e de hiperpermeabilidade vascular, com subsequente hipovolemia e hemoconcentração. Relata-se um caso de síndrome espontânea em uma gestação única. Trata-se de gravidez espontânea com 12 semanas de idade gestacional. A gravidez ocorreu sem intercorrências até 11 semanas de idade gestacional. Após, a gestante passou a se queixar de distensão abdominal progressiva, associada com desconforto abdominal. A paciente não relatava outros sintomas. A ultrassonografia de rotina no primeiro trimestre mostrou ovários aumentados com múltiplos cistos e ascite. No momento da internação, a paciente apresentava-se hemodinamicamente estável, com β-hCG sérico de 24.487mUI/mL, hormônio estimulante da tireoide de 2,2µUI/m e T4 livre de 1,8ng/dL, ou seja, valores dentro dos par

  3. IP Chemo for Ovarian Cancer is Underused

    Science.gov (United States)

    Use of intraperitoneal chemotherapy, along with intravenous chemotherapy, improves survival in some women with advanced ovarian cancer, but its use in clinical practice has been limited, according to a new study.

  4. Ovarian Cancer Stem Cells: A New Target for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Qinglei Zhan

    2013-01-01

    Full Text Available Ovarian cancer is a highly lethal disease among all gynecologic malignancies and is the fifth leading cause of cancer-related death in women. Although the standard combination of surgery and chemotherapy was initially effective in patients with ovarian cancer, disease relapse commonly occurred due to the generation of chemoresistance. It has been reported that cancer stem cells (CSCs are involved in drug resistance and cancer recurrence. Over the past decades, increasing studies have been done to identify CSCs from human ovarian cancer cells. The present paper will summarize different investigations on ovarian CSCs, including isolation, mechanisms of chemoresistance, and therapeutic approaches. Although there are still numerous challenges to translate basic research to clinical applications, understanding the molecular details of CSCs is essential for developing effective strategies to prevent ovarian cancer and its recurrence.

  5. 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.......8). Similar increased risks of serous and endometrioid tumors were found with estrogen/progestin therapy, whereas no association was found with mucinous tumors. Consistent with results from recent cohort studies, the authors found that ovarian cancer risk varied according to tumor histology. The types...... of ovarian tumors should be given attention in future studies....

  6. 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 cancer...... as a control group. Unsupervised cluster analysis identified two distinct subgroups related to genetic complexity. Sporadic and HBOC associated tumors had complex genetic profiles with an average 41% of the genome altered, whereas the mismatch repair defective tumors had stable genetic profiles...... 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....

  7. A case report of spontaneous pregnancy during hormonal replacement therapy for premature ovarian failure

    Directory of Open Access Journals (Sweden)

    Mahbod Ebrahimi

    2011-01-01

    Full Text Available Background: Premature ovarian failure (POF is a common condition; its incidence is estimated to be as great as 1 in 100 by the age of 40 years. Physiologic replacement of ovarian steroid hormones seems rational until the age of normal menopause. Temporary return of ovarian function and pregnancy may occur rarely in women with POF. We report a case of POF who conceived during hormone replacement therapy.Case: A 30 years-old woman with confirmed POF after pelvic surgery and sever emotional stress conceived spontaneously.Conclusion: Return of ovarian function and achievement of pregnancy is possible in women with POF.

  8. A case report of spontaneous pregnancy during hormonal replacement therapy for premature ovarian failure.

    Science.gov (United States)

    Akbari Asbagh, Firoozeh; Ebrahimi, Mahbod

    2011-01-01

    Premature ovarian failure (POF) is a common condition; its incidence is estimated to be as great as 1 in 100 by the age of 40 years. Physiologic replacement of ovarian steroid hormones seems rational until the age of normal menopause. Temporary return of ovarian function and pregnancy may occur rarely in women with POF. We report a case of POF who conceived during hormone replacement therapy. A 30 years-old woman with confirmed POF after pelvic surgery and sever emotional stress conceived spontaneously. Return of ovarian function and achievement of pregnancy is possible in women with POF.

  9. Increased COX-2 expression in patients with ovarian cancer | Lin ...

    African Journals Online (AJOL)

    The pathogenesis of ovarian cancer remains poorly understood. Genome-wide gene expression profiling can provide novel genetic data involved in the pathogenesis of disease. In this study, using normal ovarian surface epithelium and abnormal ovarian surface epithelium of patients with ovarian cancer as models for ...

  10. The predictive value of ovarian reserve tests for spontaneous pregnancy in subfertile ovulatory women

    NARCIS (Netherlands)

    Haadsma, M. L.; Groen, H.; Fidler, V.; Bukman, A.; Roeloffzen, E. M. A.; Groenewoud, E. R.; Broekmans, F. J. M.; Heineman, M. J.; Hoek, A.

    BACKGROUND: The predictive value of ovarian reserve tests (ORTs) for spontaneous pregnancy is unclear. Our study aimed to determine whether ORTs have added value to previously identified prognostic factors for spontaneous pregnancy in subfertile ovulatory couples. METHODS: A prospective cohort study

  11. Nightshift work and risk of ovarian cancer.

    Science.gov (United States)

    Bhatti, Parveen; Cushing-Haugen, Kara L; Wicklund, Kristine G; Doherty, Jennifer A; Rossing, Mary Anne

    2013-04-01

    Animal evidence suggests that circadian disruption may be associated with ovarian cancer, though very little epidemiological work has been done to assess this potential association. We evaluated the association between self-reported nightshift work, a known circadian disruptor, and ovarian cancer in a population-based case-control study. The study included 1101 women with invasive epithelial ovarian cancer, 389 women with borderline epithelial ovarian tumours and 1832 controls and was conducted in western Washington state. Shift work data were collected as part of inperson interviews. Working the nightshift was associated with an increased risk of invasive (OR=1.24, 95% CI 1.04 to 1.49) and borderline (OR=1.48, 95% CI 1.15 to 1.90) tumours; however, we observed little evidence that risks increased with increasing cumulative duration of nightshift work, and risks were not elevated in the highest duration category (>7 nightshift work-years). Increased risks were restricted to women who were 50 years of age and older and to serous and mucinous histologies of invasive and borderline tumours. There was suggestive evidence of a decreased risk of ovarian cancer among women reporting a preference for activity during evenings rather than mornings. We found evidence suggesting an association between shift work and ovarian cancer. This observation should be followed up in future studies incorporating detailed assessments of diurnal preference (ie, chronotype) in addition to detailed data on shift schedules.

  12. The genetics of breast and ovarian cancer.

    Science.gov (United States)

    Ford, D; Easton, D F

    1995-10-01

    A number of genes are known to be involved in inherited susceptibility to breast and/or ovarian cancer. In the context of high-risk families the most important genes are BRCA1 on chromosome 17q, which is associated with a high penetrance of both breast and ovarian cancer, and BRCA2 on chromosome 13q, which causes a high risk of breast cancer but a lower risk of ovarian cancer. Other high-risk cancer genes that confer increased risks of breast or ovarian cancer in addition to other cancers include the hereditary non-polyposis colorectal cancer genes and the TP53 gene, which causes breast cancer as part of the Li-Fraumeni syndrome. The predisposing mutations in these genes are relatively rare in the population. More common genes which are associated with an increased, but lower, risk of breast cancer are the ataxiatelangiectasia gene and the HRAS1 gene. This paper reviews recent progress in mapping and cloning of these susceptibility genes, and provides estimates of the cancer risks associated with each gene and the frequency of predisposing mutations.

  13. Survival of ovarian cancer patients in Denmark

    DEFF Research Database (Denmark)

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

    2016-01-01

    linked via the patients' personal identification number and the analyses included data on cancer stage, age, survival, surgery status and comorbidity. The computed outcome measures were age-adjusted mortality rates and age-adjusted overall and relative survival rates for one and five years. RESULTS: We......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...

  14. Is hysterectomy needed in ovarian cancer?

    Science.gov (United States)

    Chitrathara, K; Sheikh, Z A; Vijaykumar, D K; Kuriakose, S; Anupama, R; Nandeesh, M

    2011-01-01

    Hysterectomy is an integral part of ovarian cancer surgery. The authors have evaluated the uterine involvement in ovarian cancer in this study. Conventionally, removal of the uterus is considered an essential part of ovarian cancer surgery, but rationale for same in absence of its gross involvement is questionable. Aim of this study was to evaluate the microscopic involvement of uterus in ovarian cancer and whether there are any predictors of uterine involvement. Retrospective study. The authors analyzed 128 patients of epithelial ovarian cancer (EOC) operated from 2004 January to 2008 June, who had not undergone hysterectomy previously. Data regarding their demographic, clinical, and pathological findings was collected and analyzed. Chi-square test. Most of our patients (n=111) presented with stage III or above. Serous carcinoma was the most common histology encountered (86.7%). Uterus was grossly involved in only 19 patients and microscopic involvement was noted in 20 patients. Only one patient with absence of gross involvement had microscopic disease in the uterus. Involvement of the uterus was found to be independent of stage, type of tumor, laterality, and preoperative chemotherapy. The grade of tumor and gross uterine involvement were only factors that showed statistically significant correlation with microscopic uterine involvement. Only one patient had synchronous endometrial cancer. Uterine involvement in EOC is not common. Absence of gross uterine involvement reliably predicts absence of microscopic disease.

  15. Hereditary ovarian cancer: beyond the usual suspects.

    Science.gov (United States)

    Pennington, Kathryn P; Swisher, Elizabeth M

    2012-02-01

    In the past, hereditary ovarian carcinoma was attributed almost entirely to mutations in BRCA1 and BRCA2, with a much smaller contribution from mutations in DNA mismatch repair genes. Recently, three new ovarian cancer susceptibility genes have been identified: RAD51C, RAD51D, and BRIP1. In addition, germline mutations in women with ovarian carcinoma have been recently identified in many of the previously identified breast cancer genes in the Fanconi anemia (FA)-BRCA pathway. While mutations in genes other than BRCA1 and BRCA2 are each individually rare, together they make up a significant proportion of cases. With at least 16 genes implicated in hereditary ovarian cancer to date, comprehensive testing for ovarian cancer risk will require assessment of many genes. As the cost of genomic sequencing continues to fall, the practice of evaluating cancer susceptibility one gene at a time is rapidly becoming obsolete. New advances in genomic technologies will likely accelerate the discovery of additional cancer susceptibility genes and increase the feasibility of comprehensive evaluation of multiple genes simultaneously at low cost. Improved recognition of inherited risk will identify individuals who are candidates for targeted prevention. In addition, identifying inherited mutations in a variety of FA-BRCA pathway genes may aid in identifying individuals who will selectively benefit from PARP inhibitors. Copyright © 2011. Published by Elsevier Inc.

  16. 77 FR 55095 - National Ovarian Cancer Awareness Month, 2012

    Science.gov (United States)

    2012-09-06

    ... Proclamation This year, thousands of American women will lose their lives to ovarian cancer. They are mothers... campaign, we are working to raise awareness about the signs and symptoms of ovarian cancer. The Affordable...

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

    DEFF Research Database (Denmark)

    Nyhøj Heidemann, Lene; 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....

  18. Levels of Distress in Women at Risk for Ovarian Cancer

    National Research Council Canada - National Science Library

    Kash, Kathryn M

    2008-01-01

    The overall goal of this study was to determine the levels of distress in women with a family history of ovarian cancer and to identify the mediating factors between risk of developing ovarian cancer and distress...

  19. History of Comorbidities and Survival of Ovarian Cancer Patients, Results from the Ovarian Cancer Association Consortium

    DEFF Research Database (Denmark)

    Minlikeeva, Albina N; Freudenheim, Jo L; Eng, Kevin H

    2017-01-01

    carcinoma who participated in 23 studies included in the Ovarian Cancer Association Consortium, we explored associations between histories of endometriosis; asthma; depression; osteoporosis; and autoimmune, gallbladder, kidney, liver, and neurological diseases and overall and progression-free survival...... with ovarian cancer outcome in the overall sample nor in strata defined by histologic subtype, weight status, age at diagnosis, or stage of disease (local/regional vs. advanced).Conclusions: Histories of endometriosis; asthma; depression; osteoporosis; and autoimmune, gallbladder, kidney, liver, or neurologic......Background: Comorbidities can affect survival of ovarian cancer patients by influencing treatment efficacy. However, little evidence exists on the association between individual concurrent comorbidities and prognosis in ovarian cancer patients.Methods: Among patients diagnosed with invasive ovarian...

  20. 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.

  1. Use of analgesic drugs and risk of ovarian cancer

    DEFF Research Database (Denmark)

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

    2012-01-01

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

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

    DEFF Research Database (Denmark)

    Madsen, C; Baandrup, Louise; Dehlendorff, Christian

    2015-01-01

    OBJECTIVE: According to the recent theories on the ovarian cancer origin, any protective effect of tubal ligation may vary with histologic subtype of ovarian cancer. Furthermore, bilateral salpingectomy may represent an opportunity for surgical prevention of serous ovarian cancer. DESIGN: Nationw......OBJECTIVE: According to the recent theories on the ovarian cancer origin, any protective effect of tubal ligation may vary with histologic subtype of ovarian cancer. Furthermore, bilateral salpingectomy may represent an opportunity for surgical prevention of serous ovarian cancer. DESIGN...... ovarian cancer and borderline ovarian tumors stratified according to histology. RESULTS: Tubal ligation reduced overall epithelial ovarian cancer risk (odds ratios 0.87; 95% confidence interval 0.78-0.98). We observed significant risk variation according to histology (p = 0.003) with the strongest risk...... reductions associated with endometrioid cancer (odds ratios 0.66; 95% confidence interval 0.47-0.93) and epithelial ovarian cancer of "other" histology (odds ratios 0.60; 95% confidence interval 0.43-0.83). Tubal ligation was not associated with risk of borderline ovarian tumors. Finally, bilateral...

  3. 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

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

    Directory of Open Access Journals (Sweden)

    Mitsuko Furuya

    2012-07-01

    Full Text Available 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.

  5. MRI for discriminating metastatic ovarian tumors from primary epithelial ovarian cancers.

    Science.gov (United States)

    Xu, Yanhong; Yang, Jia; Zhang, Zaixian; Zhang, Guixiang

    2015-08-28

    To find specific magnetic resonance imaging (MRI) features to differentiate metastatic ovarian tumors from primary epithelial ovarian cancers. Eleven cases with metastatic ovarian tumors and 26 cases with primary malignant epithelial ovarian cancers were retrospectively studied. All features such as patient characteristics, MRI findings and biomarkers were evaluated. The differences including laterality, configuration, uniformity of locules, diffusion weighted imaging (DWI) signal of solid components and enhancement of solid portions between metastatic ovarian tumors and primary epithelial ovarian cancers were compared by Fisher's exact test. Median age of patients, the maximum diameter of lesions and biomarkers were compared by the Mann-Whitney test. Patients with metastatic ovarian tumors were younger than patients with primary epithelial ovarian cancers in the median age (P = 0.015). Patients with bilateral tumors in metastatic ovarian tumors were more than those of primary epithelial ovarian cancers (P = 0.032). The maximum diameter of lesions in metastatic ovarian tumors was smaller than that of primary epithelial ovarian cancers (P = 0.005). The locules in metastatic ovarian tumors were more uniform than those of primary epithelial ovarian cancers (P = 0.024). The enhancement of solid portions in metastatic ovarian tumors showed more moderate than that of primary epithelial ovarian cancers (P = 0.037). There was no statistically significant difference between the two groups in configuration, DWI signal of solid components and ascites. Biomarkers such as CA125 and human epididymis protein 4 (HE4) in metastatic ovarian tumors showed less elevated than that of primary epithelial ovarian cancers. Significant differences between metastatic ovarian tumors and primary epithelial ovarian cancers were found in the median age of patients, laterality, the maximum diameter of lesions, uniformity of locules, enhancement patterns of solid portions and

  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 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...... identified. Furthermore, new focus and research areas have been identified and brought into practise.    Conclusions Interdisciplinary expertise must be available to establish high quality treatment and care.  Furthermore, interdisciplinary data are an efficient baseline in planning and allocation of health...

  7. Genetics Home Reference: ovarian cancer

    Science.gov (United States)

    ... single protein building blocks (amino acids) in the p53 protein, which reduces or eliminates the protein's tumor ... of the ovary malignant tumor of the ovary ovarian carcinoma Related Information How are genetic conditions and genes ...

  8. Effects of calcium channel on ovarian cancer cells

    OpenAIRE

    Zhang, Chunyun; Li, Hailing

    2017-01-01

    The aim of the present study was to examine the effects of calcium channel protein on ovarian cancer cells. The expression of calcium channel protein in normal ovarian cells and ovarian cancer cells was detected by fluorescence quantitative PCR. Subsequently, the ovarian cancer cells were added to calcium channel protein activator media at various concentrations of 0, 1, 4, 8, 12, 16 and 20 mmol/l. The concentration of calcium ion in different samples was produced, and using an MTT assay, ova...

  9. 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 improve...

  10. Risk factors for sporadic ovarian cancer

    Directory of Open Access Journals (Sweden)

    M. M. Vysotsky

    2010-01-01

    Full Text Available The review of the literature on the problems of sporadic ovarian cancer details the present views of its disputable risk factors, such as dietary habits, body weight, contraception, and labor, and age of commencing a sexual activity. It discusses the dietary and sexual behavior model that has changed since the Neolithic, as well as the number of menses and ovulations throughout the reproductive peri- od. The works by authors dealing with the impact of smoking and alcohol consumption on the risk of ovarian cancer are analyzed.

  11. Tumour suppressor genes in sporadic epithelial ovarian cancer

    DEFF Research Database (Denmark)

    Liu, Ying; Ganesan, Trivadi S

    2002-01-01

    Ovarian cancer is the most frequent cause of death from gynaecological malignancies in the western world, and sporadic epithelial ovarian cancer is its most predominant form. The aetiology of sporadic ovarian cancer remains unknown. Genetic studies have enabled a better understanding...... 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...... research is warranted to understand fully their contribution to the pathogenesis of sporadic ovarian cancer....

  12. Development and Novel Uses of Antibodies in Epithelial Ovarian Cancer

    National Research Council Canada - National Science Library

    Curtin, John P

    2003-01-01

    .... Further understanding of the host response to epithelial cancers and the potential capability of innovative immunologic technologies to ovarian cancer may play a key role in therapeutic advances...

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

    DEFF Research Database (Denmark)

    Soegaard, Marie; Frederiksen, Kirsten; Jensen, Allan

    2009-01-01

    OBJECTIVE: To assess the risk of ovarian cancer in women with first-degree relatives with cancer at one of the four most frequent hereditary sites based on validated cancer diagnoses and to examine the association according to age at diagnosis of ovarian cancer and histology. DESIGN: Case...... with ovarian cancer family history tended to be with non-mucinous tumors. Breast cancer in one first-degree female relative was not significantly associated with risk of ovarian cancer. CONCLUSION: Ovarian cancer in a first-degree relative is a very strong predictor of epithelial ovarian cancer, especially...

  14. Mathematical Models of Breast and Ovarian Cancers

    Science.gov (United States)

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

    2016-01-01

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

  15. 6 Common Cancers - Gynecologic Cancers Cervical, Endometrial, and Ovarian

    Science.gov (United States)

    ... American women this year, more than twice the number of women who will be diagnosed with cervical (lower part of the uterus) and ovarian (female reproductive glands) cancers combined. However, in terms of 2007 ...

  16. Prognostic value of CA 125 in ovarian cyst fluid of patients with epithelial ovarian cancer.

    NARCIS (Netherlands)

    Kolwijck, E.; Span, P.N.; Thomas, C.M.G.; Bulten, J.; Sweep, F.C.; Massuger, L.F.A.G.

    2010-01-01

    Most ovarian tumors contain ovarian cyst fluid (oCF) which can be easily obtained during surgery. This is the first study that explored if CA 125 in oCF could be of prognostic value for patients with epithelial ovarian cancer (EOC). Of 54 patients with primary EOC, oCF and preoperative serum were

  17. Menopausal hormone use and ovarian cancer risk

    DEFF Research Database (Denmark)

    Beral, V; Gaitskell, K; Hermon, C

    2015-01-01

    . Adjusted Poisson regressions yielded relative risks (RRs) versus never-use. FINDINGS: During prospective follow-up, 12 110 postmenopausal women, 55% (6601) of whom had used hormone therapy, developed ovarian cancer. Among women last recorded as current users, risk was increased even with

  18. Evaluating the ovarian cancer gonadotropin hypothesis

    DEFF Research Database (Denmark)

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

    2015-01-01

    of how variability in genes involved in the gonadotropin signaling pathway impacts disease risk is warranted. METHODS: Genetic data from 41 ovarian cancer study sites were pooled and unconditional logistic regression was used to evaluate whether any of the 2185 SNPs from 11 gonadotropin signaling pathway...

  19. Quality of Life and Care Needs of Patients With Persistent or Recurrent Ovarian Cancer, Fallopian Tube Cancer, or Peritoneal Cancer

    Science.gov (United States)

    2017-05-03

    Anxiety; Fatigue; Nausea and Vomiting; Neurotoxicity Syndrome; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; 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

  20. Cisplatin induces stemness in ovarian cancer.

    Science.gov (United States)

    Wiechert, Andrew; Saygin, Caner; Thiagarajan, Praveena S; Rao, Vinay S; Hale, James S; Gupta, Nikhil; Hitomi, Masahiro; Nagaraj, Anil Belur; DiFeo, Analisa; Lathia, Justin D; Reizes, Ofer

    2016-05-24

    The mainstay of treatment for ovarian cancer is platinum-based cytotoxic chemotherapy. However, therapeutic resistance and recurrence is a common eventuality for nearly all ovarian cancer patients, resulting in poor median survival. Recurrence is postulated to be driven by a population of self-renewing, therapeutically resistant cancer stem cells (CSCs). A current limitation in CSC studies is the inability to interrogate their dynamic changes in real time. Here we utilized a GFP reporter driven by the NANOG-promoter to enrich and track ovarian CSCs. Using this approach, we identified a population of cells with CSC properties including enhanced expression of stem cell transcription factors, self-renewal, and tumor initiation. We also observed elevations in CSC properties in cisplatin-resistant ovarian cancer cells as compared to cisplatin-naïve ovarian cancer cells. CD49f, a marker for CSCs in other solid tumors, enriched CSCs in cisplatin-resistant and -naïve cells. NANOG-GFP enriched CSCs (GFP+ cells) were more resistant to cisplatin as compared to GFP-negative cells. Moreover, upon cisplatin treatment, the GFP signal intensity and NANOG expression increased in GFP-negative cells, indicating that cisplatin was able to induce the CSC state. Taken together, we describe a reporter-based strategy that allows for determination of the CSC state in real time and can be used to detect the induction of the CSC state upon cisplatin treatment. As cisplatin may provide an inductive stress for the stem cell state, future efforts should focus on combining cytotoxic chemotherapy with a CSC targeted therapy for greater clinical utility.

  1. 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...... the Curve (AUC) of 0.920 for CA125, 0.933 for HE4 and 0.946 for ROMA. The ROC curves of OC versus benign ovarian tumors shows that the CPH-I (AUC = 0.959) is equivalent with RMI (AUC = 0.958).  Conclusion: Both ROMA and CPH-I could potentially shorten the time spent before OC patients reach a tertiary...

  2. Novel nanotechnology approaches to diagnosis and therapy of ovarian cancer.

    Science.gov (United States)

    Kim, Paul S; Djazayeri, Shabdis; Zeineldin, Reema

    2011-03-01

    Ovarian carcinoma is the leading cause of death from gynecologic malignancies, which is a direct outcome of missing its diagnosis at an early stage. Approximately 75% of ovarian cancer patients are initially diagnosed with disseminated intra-abdominal disease (stages III-IV) when ~30% of patients have a 5-year survival rate. In addition to the challenge of early detection of ovarian cancer, its therapy presents several challenges including the route of therapy, resistance to therapy with recurrence of cancer, and specific targeting of ovarian cancer to reduce cytotoxic side effects. We reviewed recent literature employing nanotechnology approaches to diagnosis and therapy of ovarian cancer. Recent innovations in nanotechnology with applications in cancer diagnostics and therapy help circumvent many pre-existing problems with conventional chemotherapy and present new ways of diagnosis and therapy. Nanotechnology has promising potential in enhancing early detection of ovarian cancer and treatment of recurrent disease. Copyright © 2010 Elsevier Inc. All rights reserved.

  3. Spontaneous Ovarian Pregnancy and Over Protective Management: A Case Report

    Directory of Open Access Journals (Sweden)

    Hatice Ender Soydinç

    2016-05-01

    Full Text Available We aimed to present a case of primary ovarian pregnancy in a 31-year-old patient who presented to the emergency room with symptoms and signs of acute abdomen and positive beta HCG test. A gestation sac of 6 weeks was detected in the right ovary by transvaginal sonography. Emergency laparotomy and extirpation of the ectopic tissue was performed.

  4. 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

    genotyped using customized Illumina Infinium iSelect (iCOGS) arrays. A two-sample (summary data) MR approach was used and analyses were performed separately for all ovarian cancer (10 065 cases) and for high-grade serous ovarian cancer (4121 cases). RESULTS: The odds ratio for epithelial ovarian cancer risk...... 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.......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....

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

    DEFF Research Database (Denmark)

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

    2017-01-01

    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......, we conducted a population-based cohort study including all women from the birth cohorts 1940 to 1970 in Denmark during 1978-2012 (n = 1,318,929) to investigate the association between PID and subsequent risk of epithelial ovarian cancer. Among women in the cohort, 81,281 women were diagnosed with PID...... and 5,356 women developed ovarian cancer during follow-up through 2012. Cox regression models were used to estimate HRs and 95% confidence intervals (CI) for the association between PID and ovarian cancer, both overall and according to histotype. RESULTS: For ovarian cancer overall, we observed...

  6. 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+ ...

  7. Mucinous ovarian cancer: A therapeutic review.

    Science.gov (United States)

    Xu, Wen; Rush, Jack; Rickett, Kirsty; Coward, Jermaine I G

    2016-06-01

    Mucinous ovarian cancer represents approximately 3% of epithelial ovarian cancers (EOC). Despite this seemingly low prevalence, it remains a diagnostic and therapeutic conundrum that has resulted in numerous attempts to adopt novel strategies in managing this disease. Anecdotally, there has been a prevailing notion that established gold standard systemic regimens should be substituted for those utilised in cancers such as gastrointestinal (GI) malignancies; tumours that share more biological similarities than other EOC subtypes. This review summarises the plethora of small studies which have adopted this philosophy and influenced the design of the multinational GOG142 study, which was ultimately terminated due to poor accrual. To date, there is a paucity of evidence to support delivering 'GI style' chemotherapy for mucinous ovarian cancer over and above carboplatin-paclitaxel doublet therapy. Hence there is an urge to develop studies focused on targeted therapeutic agents driven by refined mutational analysis and conducted within the context of harmonised international collaborations. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. IKKε coordinates invasion and metastasis of ovarian cancer

    Science.gov (United States)

    Hsu, Sarah; Kim, Marianne; Hernandez, Lidia; Grajales, Valentina; Noonan, Anne; Anver, Miriam; Davidson, Ben; Annunziata, Christina M.

    2012-01-01

    I-κB kinases (IKKs) are key regulators of NF-κB signaling. Three IKK isoforms – α, β and ε – have been linked to oncogenesis, yet the precise components of NF-κB signaling in ovarian cancer have not yet been dissected. We surveyed 120 ovarian cancer specimens for IKKε expression. Notably, cytoplasmic expression was elevated in metastatic lesions relative to primary tumors (p=0.03). Therefore, we hypothesized that IKKε drives ovarian cancer metastasis. IKKε was identified previously as a breast cancer oncogene and was associated with poor clinical outcome in ovarian cancer. We now define an ovarian cancer-specific IKKε-regulated gene expression signature using stably expressed shRNA targeting IKKε. Pathway analysis of the signature indicated that IKKε regulates expression of genes involved in cell motility and inflammation. We further showed that IKKε depletion in metastatic ovarian cancer cell lines decreased growth, adhesion, and invasion. Consistently, human xenografts depleted of IKKε in mice demonstrated decreased aggressiveness, while overexpression of IKKε in a less invasive ovarian cancer cell line increased metastasis in vivo. Taken together, these data provide evidence that IKKε is a key coordinator of invasion and metastasis programs in ovarian cancer. Inhibition of IKKε signaling thus emerges as a viable therapeutic strategy in women whose ovarian cancer demonstrates aberrant activation of this pathway. PMID:22942254

  9. Super p53 for Treatment of Ovarian Cancer

    Science.gov (United States)

    2016-07-01

    killing ovarian cancer cells in vitro. This is unreported, novel finding paves the way for using super p53 for ovarian cancer treatment. Main...This is unreported, novel finding paves the way for using super p53 for ovarian cancer treatment. Main activities and objectives completed to date...What do you plan to do during the next reporting period to accomplish the goals?  Now that the basic groundwork for the experimental assays has

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

    Science.gov (United States)

    2017-10-01

    continuing work on the role of stress in ovarian cancer development indicates that chronic stress may increase risk of developing ovarian cancer. 15...advice. Dr. Poole was also a peer mentor to three post-doctoral fellows working in the CDNM. Results from the ongoing research in the role of stress in...AWARD NUMBER: W81XWH-13-1-0493 TITLE: Psychosocial Stress and Ovarian Cancer Risk: Metabolomics and Perceived Stress PRINCIPAL INVESTIGATOR

  11. The Role of Lifestyle Factors in Ovarian Cancer Prognosis

    Science.gov (United States)

    2017-10-01

    research question of how we can improve the prognosis of ovarian cancer, but rather than focus on clinical features and tumor biology, which...AWARD NUMBER: W81XWH-15-1-0502 TITLE: The Role of Lifestyle Factors in Ovarian Cancer Prognosis PRINCIPAL INVESTIGATOR: Anita Koushik...DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. October 2017 Annual 30Sep2016 - 29Sep2017 The Role of Lifestyle Factors in Ovarian Cancer Prognosis

  12. Effects of calcium channel on ovarian cancer cells.

    Science.gov (United States)

    Zhang, Chunyun; Li, Hailing

    2017-12-01

    The aim of the present study was to examine the effects of calcium channel protein on ovarian cancer cells. The expression of calcium channel protein in normal ovarian cells and ovarian cancer cells was detected by fluorescence quantitative PCR. Subsequently, the ovarian cancer cells were added to calcium channel protein activator media at various concentrations of 0, 1, 4, 8, 12, 16 and 20 mmol/l. The concentration of calcium ion in different samples was produced, and using an MTT assay, ovarian cancer cell activity in various samples was detected. Finally, a flow cytometer was used to explore the apoptosis rate. It was found that there was a significant difference between the expression of calcium channel protein in normal ovarian tissue and ovarian cancer cells (Pcancer cells to a certain extent, in a dose-dependent manner, especially when the concentration was at 12 mmol/l at which the intracellular calcium concentration was similar to that in normal ovarian cells. In conclusion, calcium ions play an important role in promoting cell proliferation of ovarian cancer cells, and they were involved in apoptosis of ovarian cancer cells to some extent, which regulates apoptosis by controlling the content of intracellular calcium.

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

    Science.gov (United States)

    2014-04-01

    synthetic progestins used in oral contraceptives enhances fatty acid synthase-dependent breast cancer cell proliferation and survival. Int. J. Oncol. 26...acid in ovarian cancer PRINCIPAL INVESTIGATOR: Xianjun Fang CONTRACTING ORGANIZATION: Virginia Commonwealth University Richmond...2011-30 December 2013 4. TITLE AND SUBTITLE Pro-lipogenic action of lysophosphatidic acid in ovarian cancer 5a. CONTRACT NUMBER 5b. GRANT

  14. Malignant bowel obstruction in advanced ovarian cancer.

    Science.gov (United States)

    Dean, Emma; Khoja, Leila; Clamp, Andrew; Jayson, Gordon C; Goonetilleke, Dilly; Conway, Alicia M; Hasan, Jurjees

    2017-03-01

    Malignant bowel obstruction (MBO) in ovarian cancer is poorly understood. This retrospective cohort study analyzed 129 patients with ovarian cancer and MBO. At presentation, 69 (53%) had platinum-resistant, 37 (29%) platinum-sensitive and 23 (18%) chemotherapy-naive disease. In patients receiving chemotherapy following the MBO episode, median overall survival (OS) was 107 days for chemotherapy-naive patients compared with 83 and 86 for platinum-sensitive or platinum-resistant patients (p = 0.98). OS was inferior for best supportive care (45 days) compared with chemotherapy (152 days) or surgery (124 days; p Bowel Obstruction Score using Eastern Cooperative Oncology Group and obstruction level discriminated patients by median OS of 181 days (neither) versus 98 days (one) versus 42 days (both; p Bowel Obstruction Score may aide treatment stratification.

  15. 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.

  16. Update on rare epithelial ovarian cancers: based on the Rare Ovarian Tumors Young Investigator Conference.

    Science.gov (United States)

    Jang, Ji Yon Agnes; Yanaihara, Nozomu; Pujade-Lauraine, Eric; Mikami, Yoshiki; Oda, Katsutoshi; Bookman, Michael; Ledermann, Jonathan; Shimada, Muneaki; Kiyokawa, Takako; Kim, Byoung Gie; Matsumura, Noriomi; Kaku, Tsunehisa; Kuroda, Takafumi; Nagayoshi, Yoko; Kawabata, Ayako; Iida, Yasushi; Kim, Jae Weon; Quinn, Michael; Okamoto, Aikou

    2017-07-01

    There has been significant progress in the understanding of the pathology and molecular biology of rare ovarian cancers, which has helped both diagnosis and treatment. This paper provides an update on recent advances in the knowledge and treatment of rare ovarian cancers and identifies gaps that need to be addressed by further clinical research. The topics covered include: low-grade serous, mucinous, and clear cell carcinomas of the ovary. Given the molecular heterogeneity and the histopathological rarity of these ovarian cancers, the importance of designing adequately powered trials or finding statistically innovative ways to approach the treatment of these rare tumors has been emphasized. This paper is based on the Rare Ovarian Tumors Conference for Young Investigators which was presented in Tokyo 2015 prior to the 5th Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup (GCIG). Copyright © 2017. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.

  17. 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

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

    Science.gov (United States)

    2018-02-06

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

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

    Science.gov (United States)

    Rasmussen, Christina B; Jensen, Allan; Albieri, Vanna; Andersen, Klaus K; Kjaer, Susanne K

    2017-01-01

    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. Using nationwide Danish registries, we conducted a population-based cohort study including all women from the birth cohorts 1940 to 1970 in Denmark during 1978-2012 (n = 1,318,929) to investigate the association between PID and subsequent risk of epithelial ovarian cancer. Among women in the cohort, 81,281 women were diagnosed with PID and 5,356 women developed ovarian cancer during follow-up through 2012. Cox regression models were used to estimate HRs and 95% confidence intervals (CI) for the association between PID and ovarian cancer, both overall and according to histotype. For ovarian cancer overall, we observed no association with PID (HR, 1.05; 95% CI, 0.92-1.20). However, in histotype-specific analyses, we found a statistically significantly increased risk of serous ovarian cancer among women with PID (HR, 1.19; 1.00-1.41; P = 0.047). Conversely, PID was not convincingly associated with risk of any of the other histotypes of ovarian cancer. PID was associated with a modestly increased risk of serous ovarian cancer, but not other histotypes. Our results indicate that PID is not a strong risk factor for ovarian cancer. Whether PID is slightly associated with risk of serous ovarian cancer has to be confirmed in other studies. Cancer Epidemiol Biomarkers Prev; 26(1); 104-9. ©2016 AACR. ©2016 American Association for Cancer Research.

  20. Obesity and survival among women with ovarian cancer: results from the Ovarian Cancer Association Consortium.

    Science.gov (United States)

    Nagle, C M; Dixon, S C; Jensen, A; Kjaer, S K; Modugno, F; deFazio, A; Fereday, S; Hung, J; Johnatty, S E; Fasching, P A; Beckmann, M W; Lambrechts, D; Vergote, I; Van Nieuwenhuysen, E; Lambrechts, S; Risch, H A; Rossing, M A; Doherty, J A; Wicklund, K G; Chang-Claude, J; Goodman, M T; Ness, R B; Moysich, K; Heitz, F; du Bois, A; Harter, P; Schwaab, I; Matsuo, K; Hosono, S; Goode, E L; Vierkant, R A; Larson, M C; Fridley, B L; Høgdall, C; Schildkraut, J M; Weber, R P; Cramer, D W; Terry, K L; Bandera, E V; Paddock, L; Rodriguez-Rodriguez, L; Wentzensen, N; Yang, H P; Brinton, L A; Lissowska, J; Høgdall, E; Lundvall, L; Whittemore, A; McGuire, V; Sieh, W; Rothstein, J; Sutphen, R; Anton-Culver, H; Ziogas, A; Pearce, C L; Wu, A H; Webb, P M

    2015-09-01

    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 collaborative analysis to assess the association between body mass index (BMI), assessed shortly before diagnosis, progression-free survival (PFS), ovarian cancer-specific survival and overall survival (OS) among women with invasive ovarian cancer. We used original data from 21 studies, which included 12 390 women with ovarian carcinoma. We combined study-specific adjusted hazard ratios (HRs) using random-effects models to estimate pooled HRs (pHR). We further explored associations by histologic subtype. Overall, 6715 (54%) deaths occurred during follow-up. A significant OS disadvantage was observed for women who were obese (BMI: 30-34.9, pHR: 1.10 (95% confidence intervals (CIs): 0.99-1.23); BMI: ⩾35, pHR: 1.12 (95% CI: 1.01-1.25)). Results were similar for PFS and ovarian cancer-specific survival. In analyses stratified by histologic subtype, associations were strongest for women with low-grade serous (pHR: 1.12 per 5 kg m(-2)) and endometrioid subtypes (pHR: 1.08 per 5 kg m(-2)), and more modest for the high-grade serous (pHR: 1.04 per 5 kg m(-2)) subtype, but only the association with high-grade serous cancers was significant. Higher BMI is associated with adverse survival among the majority of women with ovarian cancer.

  1. Statin use and mortality among ovarian cancer patients

    DEFF Research Database (Denmark)

    Verdoodt, Freija; Kjær Hansen, Merete; Kjaer, Susanne K.

    2017-01-01

    Statin use has been suggested to improve prognosis in cancer patients, however, for ovarian cancer, the evidence is sparse. From the Danish Cancer Registry, we identified patients aged 30–84 years with a histologically verified first diagnosis of epithelial ovarian cancer between 2000 and 2013....... Data on filled prescriptions, death, and potential confounding factors were obtained from nationwide registers. Cox proportional hazard regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between post-diagnostic statin use and all......-cause or ovarian cancer-specific mortality. Among 4,419 patients with epithelial ovarian cancer, post-diagnostic statin use was not statistically significantly associated with all-cause (HR: 0.90, 95% CI: 0.78–1.04) or ovarian cancer-specific mortality (HR: 0.90, 95% CI: 0.76–1.08). There was little evidence...

  2. Spontaneous rupture of an ovarian artery aneurysm: case report and review of the literature.

    Science.gov (United States)

    Chao, Lai-Wan; Chen, Chi-Hau

    2009-01-01

    Spontaneous rupture of an ovarian artery aneurysm is an extremely rare and usually life-threatening event, most often associated with pregnancy. A 46-year-old woman presented to the emergency room with left lower abdominal pain and cold sweating. Contrast-enhanced dynamic computed tomography (CT) showed a left retroperitoneal hematoma with extravasation of contrast medium. Reconstructed images of a spiral CT disclosed a leaking left ovarian artery aneurysm. An exploratory laparotomy with ligation of the aneurysm and evacuation of the hematoma was performed. This is the third case of ruptured ovarian artery aneurysm not related to pregnancy and the first reported case related to blood pressure. A review of the literature and practical considerations on this rare condition are presented. Copyright 2009 S. Karger AG, Basel.

  3. Characterization of aldehyde dehydrogenase 1 high ovarian cancer cells: Towards targeted stem cell therapy.

    Science.gov (United States)

    Sharrow, Allison C; Perkins, Brandy; Collector, Michael I; Yu, Wayne; Simons, Brian W; Jones, Richard J

    2016-08-01

    The cancer stem cell (CSC) paradigm hypothesizes that successful clinical eradication of CSCs may lead to durable remission for patients with ovarian cancer. Despite mounting evidence in support of ovarian CSCs, their phenotype and clinical relevance remain unclear. We and others have found high aldehyde dehydrogenase 1 (ALDH(high)) expression in a variety of normal and malignant stem cells, and sought to better characterize ALDH(high) cells in ovarian cancer. We compared ALDH(high) to ALDH(low) cells in two ovarian cancer models representing distinct subtypes: FNAR-C1 cells, derived from a spontaneous rat endometrioid carcinoma, and the human SKOV3 cell line (described as both serous and clear cell subtypes). We assessed these populations for stem cell features then analyzed expression by microarray and qPCR. ALDH(high) cells displayed CSC properties, including: smaller size, quiescence, regenerating the phenotypic diversity of the cell lines in vitro, lack of contact inhibition, nonadherent growth, multi-drug resistance, and in vivo tumorigenicity. Microarray and qPCR analysis of the expression of markers reported by others to enrich for ovarian CSCs revealed that ALDH(high) cells of both models showed downregulation of CD24, but inconsistent expression of CD44, KIT and CD133. However, the following druggable targets were consistently expressed in the ALDH(high) cells from both models: mTOR signaling, her-2/neu, CD47 and FGF18/FGFR3. Based on functional characterization, ALDH(high) ovarian cancer cells represent an ovarian CSC population. Differential gene expression identified druggable targets that have the potential for therapeutic efficacy against ovarian CSCs from multiple subtypes. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Aberrant expression of BARD1 in breast and ovarian cancers with poor prognosis.

    Science.gov (United States)

    Wu, Jian-Yu; Vlastos, Anne-Therese; Pelte, Marie-Françoise; Caligo, Maria-Adelaide; Bianco, Andrea; Krause, Karl-Heinz; Laurent, Geoffrey J; Irminger-Finger, Irmgard

    2006-03-01

    Mutations in tumor-suppressor gene BARD1 have been found in inherited and spontaneous breast, ovarian and uterine cancers. BARD1 plays a critical role in DNA repair and ubiquitination as binding partner of BRCA1, with which it colocalizes to nuclear dots. Independently of BRCA1, BARD1 can induce p53-dependent apoptosis in response to genotoxic stress. Therefore, BARD1 or p53 might be defective in cancer cells spared from apoptosis. We investigated BARD1 and p53 expression in ovarian, breast and non-small-cell lung cancers. BARD1 expression was highly upregulated and cytoplasmic in most cancer cells, while weak nuclear staining was observed in the surrounding normal tissue. Maximal BARD1 expression was associated with the most malignant ovarian cancer, clear cell carcinoma. In breast cancer, BARD1 expression was correlated with poor differentiation and large tumor size, established factors of poor prognosis, as well as short disease-free survival. In contrast to breast and ovarian cancers, no correlation of BARD1 expression with either grade or stage could be determined for lung cancer. RT-PCR, performed on 10 ovarian cancers, revealed absence of the 5' portion of the BARD1 transcript in 7 tumors, and sequencing of the remaining 3 identified a missense mutation (A1291G) resulting in an amino acid change of glutamine 406 to arginine. These data suggest that genetic and epigenetic changes might lead to elevated cytoplasmic expression of BARD1 and that cytoplasmic BARD1 might be a poor prognostic factor for breast and ovarian cancers. (c) 2005 Wiley-Liss, Inc.

  5. Ovarian Cancer Risk Factors by Histologic Subtype: An Analysis From the Ovarian Cancer Cohort Consortium

    Science.gov (United States)

    Poole, Elizabeth M.; Trabert, Britton; White, Emily; Arslan, Alan A.; Patel, Alpa V.; Setiawan, V. Wendy; Visvanathan, Kala; Weiderpass, Elisabete; Adami, Hans-Olov; Black, Amanda; Bernstein, Leslie; Brinton, Louise A.; Buring, Julie; Butler, Lesley M.; Chamosa, Saioa; Clendenen, Tess V.; Dossus, Laure; Fortner, Renee; Gapstur, Susan M.; Gaudet, Mia M.; Gram, Inger T.; Hartge, Patricia; Hoffman-Bolton, Judith; Idahl, Annika; Jones, Michael; Kaaks, Rudolf; Kirsh, Victoria; Koh, Woon-Puay; Lacey, James V.; Lee, I-Min; Lundin, Eva; Merritt, Melissa A.; Onland-Moret, N. Charlotte; Peters, Ulrike; Poynter, Jenny N.; Rinaldi, Sabina; Robien, Kim; Rohan, Thomas; Sandler, Dale P.; Schairer, Catherine; Schouten, Leo J.; Sjöholm, Louise K.; Sieri, Sabina; Swerdlow, Anthony; Tjonneland, Anna; Travis, Ruth; Trichopoulou, Antonia; van den Brandt, Piet A.; Wilkens, Lynne; Wolk, Alicja; Yang, Hannah P.; Zeleniuch-Jacquotte, Anne; Tworoger, Shelley S.

    2016-01-01

    Purpose An understanding of the etiologic heterogeneity of ovarian cancer is important for improving prevention, early detection, and therapeutic approaches. We evaluated 14 hormonal, reproductive, and lifestyle factors by histologic subtype in the Ovarian Cancer Cohort Consortium (OC3). Patients and Methods Among 1.3 million women from 21 studies, 5,584 invasive epithelial ovarian cancers were identified (3,378 serous, 606 endometrioid, 331 mucinous, 269 clear cell, 1,000 other). By using competing-risks Cox proportional hazards regression stratified by study and birth year and adjusted for age, parity, and oral contraceptive use, we assessed associations for all invasive cancers by histology. Heterogeneity was evaluated by likelihood ratio test. Results Most risk factors exhibited significant heterogeneity by histology. Higher parity was most strongly associated with endometrioid (relative risk [RR] per birth, 0.78; 95% CI, 0.74 to 0.83) and clear cell (RR, 0.68; 95% CI, 0.61 to 0.76) carcinomas (P value for heterogeneity [P-het] < .001). Similarly, age at menopause, endometriosis, and tubal ligation were only associated with endometrioid and clear cell tumors (P-het ≤ .01). Family history of breast cancer (P-het = .008) had modest heterogeneity. Smoking was associated with an increased risk of mucinous (RR per 20 pack-years, 1.26; 95% CI, 1.08 to 1.46) but a decreased risk of clear cell (RR, 0.72; 95% CI, 0.55 to 0.94) tumors (P-het = .004). Unsupervised clustering by risk factors separated endometrioid, clear cell, and low-grade serous carcinomas from high-grade serous and mucinous carcinomas. Conclusion The heterogeneous associations of risk factors with ovarian cancer subtypes emphasize the importance of conducting etiologic studies by ovarian cancer subtypes. Most established risk factors were more strongly associated with nonserous carcinomas, which demonstrate challenges for risk prediction of serous cancers, the most fatal subtype. PMID:27325851

  6. Ovarian Cancer Risk Factors by Histologic Subtype: An Analysis From the Ovarian Cancer Cohort Consortium.

    Science.gov (United States)

    Wentzensen, Nicolas; Poole, Elizabeth M; Trabert, Britton; White, Emily; Arslan, Alan A; Patel, Alpa V; Setiawan, V Wendy; Visvanathan, Kala; Weiderpass, Elisabete; Adami, Hans-Olov; Black, Amanda; Bernstein, Leslie; Brinton, Louise A; Buring, Julie; Butler, Lesley M; Chamosa, Saioa; Clendenen, Tess V; Dossus, Laure; Fortner, Renee; Gapstur, Susan M; Gaudet, Mia M; Gram, Inger T; Hartge, Patricia; Hoffman-Bolton, Judith; Idahl, Annika; Jones, Michael; Kaaks, Rudolf; Kirsh, Victoria; Koh, Woon-Puay; Lacey, James V; Lee, I-Min; Lundin, Eva; Merritt, Melissa A; Onland-Moret, N Charlotte; Peters, Ulrike; Poynter, Jenny N; Rinaldi, Sabina; Robien, Kim; Rohan, Thomas; Sandler, Dale P; Schairer, Catherine; Schouten, Leo J; Sjöholm, Louise K; Sieri, Sabina; Swerdlow, Anthony; Tjonneland, Anna; Travis, Ruth; Trichopoulou, Antonia; van den Brandt, Piet A; Wilkens, Lynne; Wolk, Alicja; Yang, Hannah P; Zeleniuch-Jacquotte, Anne; Tworoger, Shelley S

    2016-08-20

    An understanding of the etiologic heterogeneity of ovarian cancer is important for improving prevention, early detection, and therapeutic approaches. We evaluated 14 hormonal, reproductive, and lifestyle factors by histologic subtype in the Ovarian Cancer Cohort Consortium (OC3). Among 1.3 million women from 21 studies, 5,584 invasive epithelial ovarian cancers were identified (3,378 serous, 606 endometrioid, 331 mucinous, 269 clear cell, 1,000 other). By using competing-risks Cox proportional hazards regression stratified by study and birth year and adjusted for age, parity, and oral contraceptive use, we assessed associations for all invasive cancers by histology. Heterogeneity was evaluated by likelihood ratio test. Most risk factors exhibited significant heterogeneity by histology. Higher parity was most strongly associated with endometrioid (relative risk [RR] per birth, 0.78; 95% CI, 0.74 to 0.83) and clear cell (RR, 0.68; 95% CI, 0.61 to 0.76) carcinomas (P value for heterogeneity [P-het] < .001). Similarly, age at menopause, endometriosis, and tubal ligation were only associated with endometrioid and clear cell tumors (P-het ≤ .01). Family history of breast cancer (P-het = .008) had modest heterogeneity. Smoking was associated with an increased risk of mucinous (RR per 20 pack-years, 1.26; 95% CI, 1.08 to 1.46) but a decreased risk of clear cell (RR, 0.72; 95% CI, 0.55 to 0.94) tumors (P-het = .004). Unsupervised clustering by risk factors separated endometrioid, clear cell, and low-grade serous carcinomas from high-grade serous and mucinous carcinomas. The heterogeneous associations of risk factors with ovarian cancer subtypes emphasize the importance of conducting etiologic studies by ovarian cancer subtypes. Most established risk factors were more strongly associated with nonserous carcinomas, which demonstrate challenges for risk prediction of serous cancers, the most fatal subtype. © 2016 by American Society of Clinical Oncology.

  7. 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...... to tumor behavior and histotype. We pooled data from 13 case-control studies, conducted between 1989 and 2009, from the Ovarian Cancer Association Consortium (OCAC), including 9,162 women with ovarian cancers, 2,354 women with borderline tumors, and 14,736 control participants. Study-specific odds ratios...... were estimated and subsequently combined into a pooled odds ratio using a random-effects model. A history of PID was associated with an increased risk of borderline tumors (pooled odds ratio (pOR) = 1.32, 95% confidence interval (CI): 1.10, 1.58). Women with at least 2 episodes of PID had a 2-fold...

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

    OpenAIRE

    Ma, Yu-mei; Zhao, Shan

    2016-01-01

    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 addi...

  9. Radioimmunoscintigraphy in patients with ovarian cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kalofonos, H.P.; Onienadum, A. [Patras Hospital, Rion (Greece). Dept. of Medicine/Oncology; Giannakenas, C.; Apostolopoulos, D.; Vassilakos, J. [Patras Hospital, Rion (Greece). Dept. of Nuclear Medicine; Kosmas, C.; Epenetos, A.A. [Hammersmith Hospital, London (United Kingdom). Dept. of Clinical Oncology; Petsas, T. [Patras Hospital, Rion (Greece). Dept. of Radiology; Dimopoulos, D. [Patras Hospital, Rion (Greece). Dept. of Gynecology

    1999-11-01

    The targeting potential of three different monoclonal antibodies (MAbs) was assessed in patients with ovarian cancer. HMFG1, OC-125 and H17E2 labelled with {sup 111}In or {sup 123}I were evaluated prospectively for their ability to localize ovarian tumour. Forty two patients with ovarian cancer, aged 40-78 years (media=58 years) were studied using OC-125 (n=9), HMFG1 (n=11) and H17E2 (n=22). Imaging data were compared with the CT and the surgical findings. Presence of tumour was confirmed in 35/42 (83%) patients (8/9 OC-125, 10/11 HMFG1 and 17/22 H17E2) and correlated well with the conventional radiology diagnostic methods. One patient with a negative H17E2 scan and a large abdominal mass detected at laparotomy revealed a PLAP-negative tumour on immunohistochemistry. Scintigraphy revealed the presence of active disease, confirmed by laparotomy/laparoscopy in 6/8 patients considered to be in clinical remission. The sensitivity of the method was high enough and the diagnostic contribution of this approach should be further evaluated. (orig.)

  10. Abnormal CA-125 levels in menopausal women without ovarian cancer.

    Science.gov (United States)

    Terada, Keith Y; Elia, Jennifer; Kim, Robert; Carney, Michael; Ahn, Hyeong Jun

    2014-10-01

    To determine if an abnormal CA-125 level in a menopausal female without ovarian cancer is associated with an increase in mortality. The Prostate, Lung, Colorectal, and Ovarian Cancer Screening Randomized Controlled (PLCO) Trial is a large multicenter prospective trial conducted by the National Cancer Institute (NCI). Over 78,000 healthy women aged 55-74 were randomized to a screening arm versus a usual medical care arm to evaluate the efficacy of screening in reducing mortality due to ovarian cancer. Women in the screening arm underwent annual screening for ovarian cancer with transvaginal ultrasound and CA-125 levels. There were 38,818 patients without ovarian cancer that had at least one CA-125 level drawn; 1201 (3.09%) had at least one abnormal level. The current study compares mortality in patients that had one or more abnormal CA-125 levels without ovarian cancer versus those with all normal levels. Patients with one or more abnormal CA-125 levels, without ovarian cancer, had a significantly higher mortality than patients with all normal CA-125 levels in the PLCO screening trial (pCA-125 and without ovarian cancer are exposed to an increased risk of premature mortality. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. 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.

  12. Novel population of small tumour-initiating stem cells in the ovaries of women with borderline ovarian cancer

    Science.gov (United States)

    Virant-Klun, Irma; Stimpfel, Martin

    2016-01-01

    Small stem cells with diameters of up to 5 μm previously isolated from adult human ovaries indicated pluripotency and germinal lineage, especially primordial germ cells, and developed into primitive oocyte-like cells in vitro. Here, we show that a comparable population of small stem cells can be found in the ovarian tissue of women with borderline ovarian cancer, which, in contrast to small stem cells in “healthy” ovaries, formed spontaneous tumour-like structures and expressed some markers related to pluripotency and germinal lineage. The gene expression profile of these small putative cancer stem cells differed from similar cells sorted from “healthy” ovaries by 132 upregulated and 97 downregulated genes, including some important forkhead box and homeobox genes related to transcription regulation, developmental processes, embryogenesis, and ovarian cancer. These putative cancer stem cells are suggested to be a novel population of ovarian tumour-initiating cells in humans. PMID:27703207

  13. 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.

  14. Screening and prevention of ovarian cancer | Chesang | East African ...

    African Journals Online (AJOL)

    Objective: To present a review of screening methods for ovarian cancer and preventive strategies. Data source: Relevant literature was identified through a search of the MEDLINE, EMBASE and CINAHL databases. Study Selection: Recent Studies assessing methods used in prevention of and screening for ovarian cancer ...

  15. Ovarian Cancer in Ghana, a 10 Year Histopathological Review of ...

    African Journals Online (AJOL)

    AJRH Managing Editor

    Akakpo et al. Ovarian Cancer, Ghana. African Journal of Reproductive Health December 2015; 19 (4): 102. ORIGINAL RESEARCH ARTICLE. Ovarian Cancer in Ghana, a 10 Year Histopathological Review of. Cases at Korle Bu Teaching Hospital. Patrick K. Akakpo. 1*. , Leonard Derkyi-Kwarteng. 1. , Richard K. Gyasi. 2.

  16. Antigen-specific active immunotherapy for ovarian cancer

    NARCIS (Netherlands)

    Leffers, Ninke; Daemen, Toos; Helfrich, Wijnand; Boezen, H. Marike; Cohlen, Ben J.; Melief, Cornelis J. M.; Nijman, Hans W.

    2014-01-01

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

  17. 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

  18. 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....

  19. 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....

  20. Polycystic ovary syndrome, oligomenorrhea, and risk of ovarian cancer histotypes

    DEFF Research Database (Denmark)

    Harris, Holly R; Babic, Ana; Webb, Penelope M

    2018-01-01

    BACKGROUND: Polycystic ovary syndrome (PCOS), and one if its distinguishing characteristics, oligomenorrhea, have both been associated with ovarian cancer risk in some but not all studies. However, these associations have been rarely been examined by ovarian cancer histotypes which may explain...

  1. Increased COX-2 expression in patients with ovarian cancer

    African Journals Online (AJOL)

    ajl yemi

    2011-10-26

    Oct 26, 2011 ... Risk factors include increasing age, estrogen replacement therapy, a family history of ovarian and/or breast cancer, and nulliparity, whereas the oral contraceptive pill (OCP) decreases risk. (Crijns et al., 2003; Hall et al., 2004). However, the cause and molecular mechanisms of ovarian cancer remain.

  2. 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....

  3. 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....

  4. 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...

  5. [Proteomics and biomarkers for detection of ovarian cancer].

    Science.gov (United States)

    Kacerovský, M; Tambor, V; Lenco, J; Tosner, J

    2009-06-01

    The purpose of this study was to focuse on recent developments on the evolving field of biomarker discovery and validation techniques using proteomics platforms for ovarian cancer. Review. Department of Obstetrics and Gynecology Medical Faculty Charles University Hradec Kralove. Institute of Molecular Pathology. Faculty of Military Health Sciences, University of Defense, Hradec Kralove. The last decade has seen major changes in the technologies used to identify markers for diagnosing early stages of ovarian cancer. Currently the major developments were made in three distinct areas: protein profilig, highthroughput validation techniques and solid and liquid phase protein microarray platforms for analyzing candidate markers across stages hold significant of ovarian cancer. These new technologies hold significant promise in identifying more robust markers for ovarian cancer. The present review summarizes the results of clinical and experimental research on biomarkers of ovarian cancer.

  6. 75 FR 54451 - National Ovarian Cancer Awareness Month, 2010

    Science.gov (United States)

    2010-09-07

    ... claim more lives than any other gynecologic cancer. During National Ovarian Cancer Awareness Month, we... Control and Prevention, and the Department of Defense all play vital roles in reducing the burden of this...

  7. Combining Drugs to Treat Ovarian Cancer - Annual Plan

    Science.gov (United States)

    Approximately 70 percent of women diagnosed with ovarian cancer will die from the disease. Read about the NCI-funded combination drug trial that has successfully treated Betsy Brauser's recurrent cancer.

  8. Genetic Modifiers of Ovarian Cancer

    Science.gov (United States)

    2014-08-01

    unselected for family history : a combined analysis of 22 studies. Am J Hum Genet 72:1117–1130. Antoniou AC, Beesley J, McGuffog L, Sinilnikova OM, Healey S...unselected for family history : a combined analysis of 22 studies. Am J Hum Genet 72: 1117–1130. 2. Antoniou AC, Chenevix-Trench G (2010) Common genetic ...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

  9. Prophylactic salpingectomy and ovarian cancer: An evidence-based analysis

    Directory of Open Access Journals (Sweden)

    Tricia Dewi Anggraeni

    2018-01-01

    Full Text Available Introduction: One of the ovarian carcinogenesis theories was the presence of premalignant cells in the epithelium of the fallopian tube. Therefore, the prophylactic salpingectomy during benign gynecological surgery is now expected as the attempt to reduce the ovarian cancer incidence. We studied the effect of prophylactic bilateral salpingectomy (PBS in reducing the ovarian cancer incidence. Methods: This evidence-based report resulted from critical appraisal of 5 articles. It is aimed to answer our clinical question, can bilateral prophylactic salpingectomy reduce the incidence of ovarian cancer among women underwent hysterectomy for benign condition or permanent contraception surgery? The search was conducted on the Cochrane Library®, PubMed®, and Embase® using keywords of “prophylactic salpingectomy,” and “ovarian cancer incidence.” Reference lists of relevant articles were searched for other possibly relevant articles. Results: Five studies were included in our appraisal. The incidence of ovarian cancer among women underwent prophylactic salpingectomy is lower compared to women who were not underwent any intervention (2.2% to 13% and 4.75% to 24.4%. The salpingectomy may reduce 29.2% to 64% of ovarian cancer incidence. No significant effect of PBS to ovarian function, quality of life, sexuality, surgery duration, and its cost-effective profile were also found throughout our literature study. Conclusion: PBS is suggested to be performed for women during benign gynecological surgery as a primary preventive strategy of ovarian cancer. PBS is a cost-effective procedure, risk-reducing for ovarian cancer and has no significant effect to the ovarian function.

  10. Retinoid receptors in ovarian cancer: expression and prognosis.

    Science.gov (United States)

    Kaiser, P C; Körner, M; Kappeler, A; Aebi, S

    2005-09-01

    Ovarian cancer is frequently lethal despite aggressive multimodal therapy, and new therapies are therefore needed. Retinoids are potential candidate drugs: they prevent the development of ovarian carcinoma and enhance the efficacy of cytotoxic drugs in ovarian cancer cells. At present, little is known about the retinoid receptor expression in ovarian cancer. The retinoid receptors comprise two classes, retinoic acid receptors (RARs) and retinoid X receptors (RXRs), each with three subclasses, alpha, beta and gamma. We investigated the expression of the subtypes RARalpha, RARgamma, RXRalpha and RXRbeta by immunohistochemistry in ovarian cancers of 80 patients, and assessed their prognostic significance. In addition, we quantified the expression of retinoid receptor mRNA using real-time PCR and correlated the results with clinical characteristics. RARalpha and RXRbeta were highly expressed in a majority of ovarian cancers, particularly in advanced stages. High expression of RARalpha was an independent negative prognostic factor of survival in addition to FIGO stage, age and p53 accumulation. The mRNA expression of retinoid receptors did not correlate with clinical properties of the tumors. Retinoic acid receptors are frequently and strongly expressed in epithelial ovarian cancer and may be indicators of an adverse prognosis. This study provides the molecular basis for the therapeutic use of retinoids in 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. Sensitization of ovarian cancer cells to cisplatin by gold nanoparticles

    Science.gov (United States)

    Saha, Sounik; Robertson, David J.; McMeekin, Scott; Bhattacharya, Resham; Mukherjee, Priyabrata

    2014-01-01

    Recently we reported that gold nanoparticles (AuNPs) inhibit ovarian tumor growth and metastasis in mice by reversing epithelial-mesenchymal transition (EMT). Since EMT is known to confer drug resistance to cancer cells, we wanted to investigate whether anti-EMT property of AuNP could be utilized to sensitize ovarian cancer cells to cisplatin. Herein, we report that AuNPs prevent cisplatin-induced acquired chemoresistance and stemness in ovarian cancer cells and sensitize them to cisplatin. AuNPs inhibit cisplatin induced EMT, decrease the side population cells and key stem cell markers such as ALDH1, CD44, CD133, Sox2, MDR1 and ABCG2 in ovarian cancer cells. Mechanistically, AuNPs prevent cisplatin-induced activation of Akt and NF-κB signaling axis in ovarian cancer cells that are critical for EMT, stem cell maintenance and drug resistance. In vivo, AuNPs sensitize orthotopically implanted ovarian tumor to a low dose of cisplatin and significantly inhibit tumor growth via facilitated delivery of both AuNP and cisplatin. These findings suggest that by depleting stem cell pools and inhibiting key molecular pathways gold nanoparticles sensitize ovarian cancer cells to cisplatin and may be used in combination to inhibit tumor growth and metastasis in ovarian cancer. PMID:25071019

  13. OVULATION INDUCTION AGENTS AND OVARIAN CANCER

    Directory of Open Access Journals (Sweden)

    Barbara Požlep

    2001-10-01

    Full Text Available Background. Ovarian cancer is the most frequentcause of death among gynecologic malignancies. Epidemiologicaldata show that environmental, hormonal and geneticfactors are etiologically significant. Beside the already knownrisk factors, ovulation induction agents have been reported asrisk factors in literature since 1986. Over the last two decades,ovulation induction agents have been widely used in variousassisted reproduction techniques (ART. This study focusedon the question whether in patients receiving ovulation inductionagents the risk for developing pathologic processes onthe ovaries was higher than in those not receiving them, andwhether they were related to the dose and type of ovulationinduction agent.Methods. In a prospective study 380 subjects were enrolled.The study group consisted of 280 women who had undergonean ART procedure three or more times. The control group consistedof 120 infertile women, never included in an ART procedure.All the enrolled subjects underwent the same examinations:a detailed gynecological history was taken, pelvic examinationand vaginal ultrasound were performed, and a bloodsample for tumour marker CA 125 determination was taken.Statistical analysis was done using Chi-square test, t test andlogistic regression.Results. Ultrasound examination revealed pathology on thegenital tract in 136 women in the study group and in 60 womenin the control group. Differences in the incidence of ovarian,tubal and uterine pathology were not statistically significant.The analysis of the medical records showed that the incidenceof ovarian pathology was significantly higher in thestudy than in the control group (p < 0.05. We found no correlationbetween the incidence of ovarian pathology and typeor dose of ovulation induction agent. Increased CA 125 levelswere found in 12 women. In none of the women neither malignantnor borderline malignant disease was found.Conclusions. Although the analysis of the data from medicalhistory showed

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

    NARCIS (Netherlands)

    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; Miedzybrodzka, Zosia; Gregory, Helen; Morrison, Patrick; Jeffers, Lisa; Ong, Kai-Ren; Hoffman, Jonathan; Donaldson, Alan; James, Margaret; Downing, Sarah; Taylor, Amy; Murray, Alexandra; Rogers, Mark T.; McCann, Emma; Barton, David; Porteous, Mary; Drummond, Sarah; Kivuva, Emma; Searle, Anne; Goodman, Selina; Hill, Kathryn; Murday, Victoria; Bradshaw, Nicola; Snadden, Lesley; Longmuir, Mark; Watt, Catherine; Gibson, Sarah; Haque, Eshika; Tobias, Ed; Duncan, Alexis; Izatt, Louise; Langman, Caroline; Whaite, Anna; Dorkins, Huw; Barwell, Julian; Serra-Feliu, Gemma; Ellis, Ian; Houghton, Catherine; Taylor, Jane; Side, Lucy; Male, Alison; Berlin, Cheryl; Eason, Jacqueline; Collier, Rebecca; Claber, Oonagh; Jobson, Irene; McLeod, Diane; Halliday, Dorothy; Durell, Sarah; Stayner, Barbara; Shanley, Susan; Rahman, Nazneen; Houlston, Richard; Bancroft, Elizabeth; D'Mello, Lucia; Page, Elizabeth; Ardern-Jones, Audrey; Kohut, Kelly; Wiggins, Jennifer; Castro, Elena; Mitra, Anita; Robertson, Lisa; Quarrell, Oliver; Bardsley, Cathryn; Goff, Sheila; Brice, Glen; Winchester, Lizzie; Eddy, Charlotte; Tripathi, Vishakha; Attard, Virginia; Lucassen, Anneke; Crawford, Gillian; McBride, Donna; Smalley, Sarah; Sinilnikova, Olga; Barjhoux, Laure; Verny-Pierre, Carole; Giraud, Sophie; Léone, Mélanie; Buecher, Bruno; Houdayer, Claude; Moncoutier, Virginie; Belotti, Muriel; Tirapo, Carole; Bressac-de-Paillerets, Brigitte; Remenieras, Audrey; Byrede, Véronique; Caron, Olivier; Lenoir, Gilbert; Urhammer, Nancy; Sobol, Hagay; Bourdon, Violaine; Noguchi, Tetsuro; Eisinger, François; Coulet, Florence; Colas, Chrystelle; Soubrier, Florent; Coupier, Isabelle; Pujol, Pascal; Peyrat, Jean-Philippe; Fournier, Joëlle; Révilliion, Françoise; Vennin, Philippe; Adenis, Claude; Rouleau, Etienne; Lidereau, Rosette; Demange, Liliane; Nogues, Catherine; Muller, Danièle; Fricker, Jean-Pierre; Barouk-Simonet, Emmanuelle; Bonnet, Françoise; Bubien, Virginie; Sevenet, Nicolas; Longy, Michel; Toulas, Christine; Guimbaud, Rosine; Gladieff, Laurence; Feillel, Viviane; Leroux, Dominique; Dreyfus, Hélène; Rebischung, Christine; Peysselon, Megalie; Coron, Fanny; Prieur, Fabienne; Lebrun, Marine; Kientz, Caroline; Frénay, Marc; Vénat-Bouvet, Laurence; Delnatte, Capucine; Mortemousque, Isabelle; Lynch, Henry T.; Snyder, Carrie L.; Hogervorst, F. B. L.; Verhoef, S.; Verheus, M.; van't Veer, L. J.; van Leeuwen, F. E.; Collée, M.; van den Ouweland, A. M. W.; Jager, A.; Hooning, M. J.; Tilanus-Linthorst, M. M. A.; Seynaeve, C.; van Asperen, C. J.; Wijnen, J. T.; Vreeswijk, M. P.; Tollenaar, R. A.; Devilee, P.; Ligtenberg, M. J.; Hoogerbrugge, N.; Ausems, M. G.; van der Luijt, R. B.; van Os, T. A.; Gille, J. J. P.; Waisfisz, Q.; Gomez-Garcia, E. B.; van Roozendaal, C. E.; Blok, Marinus J.; Caanen, B.; Oosterwijk, J. C.; van der Hout, A. H.; Mourits, M. J.; Vasen, H. F.; Thorne, Heather; Niedermayr, Eveline; Gill, Mona; Collins, Lucine; Gokgoz, Nalan; Selander, Teresa; Weerasooriya, Nayana; Karlsson, Per; Nordlilng, Margareta; Bergman, Annika; Einbeigi, Zakaria; Liedgren, Sigrun; Borg, Åke; Loman, Niklas; Soller, Maria; Jernström, Helena; Harbst, Katja; Henriksson, Karin; Arver, Brita; von Wachenfeldt, Anna; Barbany-Bustinza, Gisela; Rantala, Johanna; Grönberg, Henrik; Stattin, Eva-Lena; Emanuelsson, Monica; Ehrencrona, Hans; Rosenquist, Richard; Dahl, Niklas

    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

  15. Genetic Modifiers of Ovarian Cancer

    Science.gov (United States)

    2014-08-01

    Athens, Greece (Yannoukakos, Fostira); Instituto de Genética Humana, Pontificia Universidad Javeriana, Bogotá, Colombia (Torres); Molecular Genetics of...education support from Succinct Health Communications and Janssen Pharmaceuticals . Dr Davidson reported having received funding from from Cancer

  16. Quality control in ovarian cancer surgery.

    Science.gov (United States)

    Aletti, Giovanni D; Peiretti, Michele

    2017-05-01

    The optimal surgical management of patients with ovarian cancer includes a thorough staging with peritoneal and retroperitoneal assessment for early disease stages and a complete debulking with the removal of all macroscopic tumor for advanced disease stages. Disparities across different institutions in terms of optimal surgical management have been described. Surgical quality control programs constitute a real possibility to ensure and improve the quality of the surgery performed. Guidelines for surgery in early and advanced disease stages have been recently reviewed by the National Comprehensive Cancer Network (NCCN), and several quality indicators (QIs) have been proposed. These QIs can be used as a powerful tool to monitor, compare, and improve the quality of surgery across different centers and institutions. Furthermore, a transparent report of surgical outcomes through the creation of National and International Networks, adherence to the NCCN guidelines, and the establishment of quality control programs with a strong training and education component are key factors in enhancing the quality of surgery for patients with ovarian cancer. Copyright © 2016. Published by Elsevier Ltd.

  17. Surgery for advanced epithelial ovarian cancer.

    Science.gov (United States)

    Hacker, Neville F; Rao, Archana

    2017-05-01

    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. Copyright © 2016. Published by Elsevier Ltd.

  18. 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...... of five additional parameters: age and amount of residual tumor. However, both in stage IB-II and stage III-IV carcinomas, the MNV increased significantly with increasing tumor grade and DNA-index. Furthermore, FIGO-stage IB-II patients had significantly smaller nuclei than patients with stage III...

  19. PDI Coamplified Genes in Ovarian Cancer

    Science.gov (United States)

    2017-08-01

    Therefore, we could not generate any data during the first year. This is a copy of our first-year progress report that goes beyond the period from 6-1-14...year we purchased several antibodies from multiple vendors and tested them in various ovarian cancer cell lines. We had to contact, test, and validate...obtained from the same mice. HE Y $ NC I$A DR $R es $ Fa t_ T$ OV CA R$ 8$ OV CA R$ 5$ SK OV 3$ TO V2 1$ Fa t$_ N$ HE Y $I nv as ion $ OV CA R$ 3$ GAPDH

  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. 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

    sensitivity (50-62% for early stage epithelial ovarian cancer) and limited specificity (94-98.5%), cancer antigen (CA) 125 (CA125) is not recommended as a screening test in asymptomatic women. The Risk of Malignancy Index, which includes CA125, transvaginal ultrasound, and menopausal status, is recommended.......0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially....

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Metformin inhibits the development and metastasis of ovarian cancer.

    Science.gov (United States)

    Wu, Buchu; Li, Shu; Sheng, Lili; Zhu, Jing; Gu, Liying; Shen, Haoran; La, Duanduan; Hambly, Brett D; Bao, Shisan; Di, Wen

    2012-09-01

    The aim of this study was to investigate the role of metformin in the regulation of development and metastasis of ovarian carcinoma cell lines in vitro and ovarian cancer in a nude mouse model in vivo. The effects of metformin on the ability of two high-metastatic potential human ovarian cancer cell lines (SKOV3 and HO8910-PM) to adhere, invade and migrate in vitro were observed by means of a cell adhesion test, cell invasion test and cell migration test. The size and number of the inoculated and metastatic tumours in vivo in a nude mouse were determined following intraperitoneal injection of metformin. Furthermore, the extent of angiogenesis (vWF) and macrophage infiltration in the tumour were determined. Proliferation, migration, invasion and adhesion of ovarian cancer cells were significantly inhibited (Pmetformin inhibited hepatic, intestinal and lung metastasis (Pmetformin inhibits the development and metastasis of ovarian cancer by reducing cellular-ECM interactions, neovascularisation and macrophage infiltration.

  4. Autoantibody biomarkers identified by proteomics methods distinguish ovarian cancer from non ovarian cancer with various CA-125 levels

    Science.gov (United States)

    Karabudak, Aykan; Hafner, Julie; Shetty, Vivekananda; Chen, Songming; Secord, Angeles Alvarez; Morse, Michael

    2013-01-01

    Purpose CA-125 has been a valuable marker for detecting ovarian cancer, however, not sensitive enough to detect early stage disease and not specific for ovarian cancer. The purpose of our study was to identify autoantibody markers that are specific for ovarian cancer regardless of CA-125 levels. Methods Top-down and iTRAQ quantitative proteomics methods were used to identify high frequency autoantibodies in ovarian cancer. Protein microarrays comprising the recombinant autoantigens were screened using serum samples from various stages of ovarian cancer with diverse levels of CA-125 as well as benign and healthy controls. ROC curve and dot blot analyses were performed to validate the sensitivity and specificity of the autoantibody markers. Results The proteomics methodologies identified >60 potential high frequency autoantibodies in ovarian cancer. Individual serum samples from ovarian cancer stages I-IV compared to control samples that were screened on a microarray containing native recombinant autoantigens revealed a panel of stage I high frequency autoantibodies. Preliminary ROC curve and dot blot analyses performed with the ovarian cancer samples showed higher specificity and sensitivity as compared to CA-125. Three autoantibody markers exhibited higher specificity in various stages of ovarian cancer with low and normal CA-125 levels. Conclusions Proteomics technologies are suitable for the identification of protein biomarkers and also the identification of autoantibody biomarkers when combined with protein microarray screening. Using native recombinant autoantigen arrays to screen autoantibody markers, it is possible to identify markers with higher sensitivity and specificity than CA-125 that are relevant for early detection of ovarian cancer. PMID:23999876

  5. Autoantibody biomarkers identified by proteomics methods distinguish ovarian cancer from non-ovarian cancer with various CA-125 levels.

    Science.gov (United States)

    Karabudak, Aykan A; Hafner, Julie; Shetty, Vivekananda; Chen, Songming; Secord, Angeles Alvarez; Morse, Michael A; Philip, Ramila

    2013-10-01

    CA-125 has been a valuable marker for detecting ovarian cancer, however, it is not sensitive enough to detect early-stage disease and not specific to ovarian cancer. The purpose of our study was to identify autoantibody markers that are specific to ovarian cancer regardless of CA-125 levels. Top-down and iTRAQ quantitative proteomics methods were used to identify high-frequency autoantibodies in ovarian cancer. Protein microarrays comprising the recombinant autoantigens were screened using serum samples from various stages of ovarian cancer with diverse levels of CA-125 as well as benign and healthy controls. ROC curve and dot blot analyses were performed to validate the sensitivity and specificity of the autoantibody markers. The proteomics methodologies identified more than 60 potential high-frequency autoantibodies in ovarian cancer. Individual serum samples from ovarian cancer stages I-IV compared to control samples that were screened on a microarray containing native recombinant autoantigens revealed a panel of stage I high-frequency autoantibodies. Preliminary ROC curve and dot blot analyses performed with the ovarian cancer samples showed higher specificity and sensitivity as compared to CA-125. Three autoantibody markers exhibited higher specificity in various stages of ovarian cancer with low and normal CA-125 levels. Proteomics technologies are suitable for the identification of protein biomarkers and also the identification of autoantibody biomarkers when combined with protein microarray screening. Using native recombinant autoantigen arrays to screen autoantibody markers, it is possible to identify markers with higher sensitivity and specificity than CA-125 that are relevant to early detection of ovarian cancer.

  6. 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

  7. Ovarian and Uterine Functions in Female Survivors of Childhood Cancers.

    Science.gov (United States)

    Oktem, Ozgur; Kim, Samuel S; Selek, Ugur; Schatmann, Glenn; Urman, Bulent

    2018-02-01

    Adult survivors of childhood cancers are more prone to developing poor reproductive and obstetrical outcomes than their siblings and the general population as a result of previous exposure to chemotherapy and radiation during childhood. Chemotherapy drugs exert cytotoxic effects systemically and therefore can damage the ovaries, leading to infertility, premature ovarian failure, and, to a lesser extent, spontaneous abortions. They have very limited or no deleterious effects on the uterus that can be recognized clinically. By contrast, radiation is detrimental to both the ovaries and the uterus, thereby causing a greater magnitude of adverse effects on the female reproductive function. These include infertility, premature ovarian failure, miscarriage, fetal growth restrictions, perinatal deaths, preterm births, delivery of small-for-gestational-age infants, preeclampsia, and abnormal placentation. Regrettably, the majority of these adverse outcomes arise from radiation-induced uterine injury and are reported at higher incidence in the adult survivors of childhood cancers who were exposed to uterine radiation during childhood in the form of pelvic, spinal, or total-body irradiation. Recent findings of long-term follow-up studies evaluating reproductive performance of female survivors provided some reassurance to female cancer survivors by documenting that pregnancy and live birth rates were not significantly compromised in survivors, including those who had been treated with alkylating agents and had not received pelvic, cranial, and total-body irradiation. We aimed in this narrative review article to provide an update on the impact of chemotherapy and radiation on the ovarian and uterine function in female survivors of childhood cancer. Adult survivors of childhood cancers are more prone to developing a number of poor reproductive and obstetrical outcomes than their siblings and the general population as a result of previous exposure to chemotherapy and radiation

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

    Science.gov (United States)

    2013-03-18

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

  9. NuMA Overexpression in Epithelial Ovarian Cancer

    OpenAIRE

    Brüning-Richardson, Anke; Bond, Jaqueline; Alsiary, Rawiah; Richardson, Julie; Cairns, David A.; McCormac, Luci; Hutson, Richard; Burns, Philip A.; Wilkinson, Nafisa; Hall, Geoff D.; Morrison, Ewan E.; Bell, Sandra M.

    2012-01-01

    Highly aneuploid tumours are common in epithelial ovarian cancers (EOC). We investigated whether NuMA expression was associated with this phenomenon. NuMA protein levels in normal and tumour tissues, ovarian cell lines and primary cultures of malignant cells derived from ovarian ascitic fluids were analysed by Affymetrix microarray analysis, immunoblotting, immunohistochemistry (IHC) and immunofluorescence (IF), with results correlated to associated clinical data. Aneuploidy status in primary...

  10. Nedd4L expression is decreased in ovarian epithelial cancer tissues compared to ovarian non-cancer tissue.

    Science.gov (United States)

    Yang, Qiuyun; Zhao, Jinghe; Cui, Manhua; Gi, Shuting; Wang, Wei; Han, Xiaole

    2015-12-01

    Recent studies have demonstrated that the neural precursor cell expressed, developmentally downregulated 4-like (Nedd4L) gene plays a role in the progression of various cancers. However, reports describing Nedd4L expression in ovarian cancer tissues are limited. A cohort (n = 117) of archival formalin-fixed, paraffin embedded resected normal ovarian epithelial tissues (n = 10), benign ovarian epithelial tumor tissues (n = 10), serous borderline ovarian epithelial tumor tissues (n = 14), mucous borderline ovarian epithelial tumor tissues (n = 11), and invasive ovarian epithelial cancer tissues (n = 72) were assessed for Nedd4L protein expression using immunohistochemistry. Nedd4L protein expression was significantly decreased in invasive ovarian epithelial cancer tissues compared to non-cancer tissues (P < 0.05). Decreased Nedd4L protein expression correlated with clinical stage, pathological grade, lymph node metastasis and survival (P < 0.05). Nedd4L protein expression may be an independent prognostic marker of ovarian cancer development. © 2015 Japan Society of Obstetrics and Gynecology.

  11. Whole abdominal radiotherapy in ovarian cancer

    International Nuclear Information System (INIS)

    Biete, A.; Valduvieco, I.; Rovirosa, A.; Farrus, B.; Casas, F.; Conill, C.

    2010-01-01

    Objectives: The aim of the study was to evaluate the clinical outcome and toxicity after adjuvant whole abdominal radiotherapy (WART) in patients with ovarian cancer. Material and methods: Ten patients with optimal cytoreduced ovarian cancer, with a mean age of 58 years (40 - 70) and stage Ic: 4, stage II: 2, stage III: 4, were treated with WART and adjuvant chemotherapy (9/10). The total radiation dose was 22.5 Gy in the whole abdomen and 42 - 45 Gy in the pelvis. Results: The mean follow-up was 8 years. The 5-year actuarial disease-free survival (DFS) was 60%, and the overall survival (OS) was 70%. Four patients had disease recurrence. The sites of recurrence were the abdomen in 2 patients and distant metastases in the other 2 patients (liver and brain metastasis). Gastrointestinal toxicity was as follows: acute 3/10 grades I and II, and late toxicity: 2/10 grades I and II, and only 1 patient developed small bowel obstruction (SBO) that required surgery. Conclusions: Whole abdominal radiotherapy after surgery and platinum-based chemotherapy achieves high locoregional disease control with an acceptable risk of acute toxicity. (authors)

  12. Brain metastases from epithelial ovarian cancer.

    Science.gov (United States)

    Tay, S-K; Rajesh, H

    2005-01-01

    Brain metastasis from epithelial ovarian cancer is uncommon. We studied the presentation, treatment, and prognosis of brain metastasis in a single institution. A retrospective review of clinical details kept in the computer database of gynecologic oncology services in a tertiary institution between 1993 and 2003 was done. A Medline search for English publications on brain metastasis from epithelial ovarian cancer was performed from 1966 to 2003. The study period included 605 patients, and 4 (0.66%) patients developed brain metastases. The patients were usually well, until they presented with hemiparesis. The median primary treatment to brain metastasis interval was 16.5 months. Three out of four cases had multiple brain metastases, and all had small-volume extracranial tumor relapses. Serum CA125 measurement was not reliable in the screening for brain metastasis. The median survival after brain metastasis was 19.5 months. Single brain metastasis can be treated with surgery. Our experience supports the prevalent published opinion that all other cases should be considered for combined radiotherapy and surgery or radiotherapy and chemotherapy. Surveillance of tumor recurrence with serum CA125 monitoring does not predict brain metastasis, which carries a poor prognosis. The best mode of management of these patients is yet to be determined. Large study with multicenter participation to establish the standard treatment is urgently needed.

  13. 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

  14. Role of Autophagy in Cisplatin Resistance in Ovarian Cancer Cells*

    Science.gov (United States)

    Wang, Juan; Wu, Gen Sheng

    2014-01-01

    Cisplatin-based treatment is the first line chemotherapy for several cancers including ovarian cancer. The development of cisplatin resistance results in treatment failure, but the underlying mechanisms are not fully understood. Here we show that the induction of autophagy plays an important role in cisplatin resistance in ovarian cancer cells. Specifically, we show that cisplatin resistance is correlated with autophagy induction in a panel of ovarian cancer cells but not in immortalized human ovarian surface epithelial cells. Mechanistically, cisplatin treatment activates ERK and subsequently promotes autophagy. The inhibition of ERK activation with MEK inhibitors or knockdown of ERK expression with siRNA decreases cisplatin-induced autophagy and subsequently sensitizes ovarian cancer cells to cisplatin-induced apoptosis. In ovarian cancer cells that have developed acquired cisplatin resistance, both ERK activation and autophagy induction are increased. Importantly, knockdown of ERK or inhibition of autophagy promotes cisplatin-induced apoptosis in acquired cisplatin-resistant cells. Collectively, our data indicate that ERK-mediated autophagy can lead to cisplatin resistance and suggest that cisplatin resistance can be overcome by inhibition of autophagy in ovarian cancer cells. PMID:24794870

  15. The Effect of Gynecologic Oncologist Availability on Ovarian Cancer Mortality

    Science.gov (United States)

    Stewart, Sherri L.; Cooney, Darryl; Hirsch, Shawn; Westervelt, Lauren; Richards, Thomas B.; Rim, Sun Hee; Thomas, Cheryll C.

    2015-01-01

    AIM To determine the association between the distribution of gynecologic oncologist (GO) and population-based ovarian cancer death rates. MATERIALS AND METHODS Data on ovarian cancer incidence and mortality in the United States (U.S.) was supplemented with U.S. census data, and analyzed in relation to practicing GOs. GO locations were geocoded to link association between county variables and GO availability. Logistic regression was used to measure areas of high and low ovarian cancer mortality, adjusting for contextual variables. RESULTS Practicing GOs were unevenly distributed in the United States, with the greatest numbers in metropolitan areas. Ovarian cancer incidence and death rates increased as distance to a practicing GO increased. A relatively small number (153) of counties within 24 miles of a GO had high ovarian cancer death rates compared to 577 counties located 50 or more miles away with high ovarian cancer death rates. Counties located 50 or more miles away from a GO practice had an almost 60% greater odds of high ovarian cancer mortality compared to those with closer practicing GOs (OR 1.59, 95% CI 1.18–2.15). CONCLUSION The distribution of GOs across the United States appears to be significantly associated with ovarian cancer mortality. Efforts that facilitate outreach of GOs to certain populations may increase geographic access. Future studies examining other factors associated with lack of GO access (e.g. insurance and other socioeconomic factors) at the individual level will assist with further defining barriers to quality ovarian cancer care in the United States. PMID:26478860

  16. Inhibitory role of prohibitin in human ovarian epithelial cancer

    Science.gov (United States)

    Jia, Lin; Ren, Jian-Min; Wang, Yi-Ying; Zheng, Yu; Zhang, Hui; Zhang, Qing; Kong, Bei-Hua; Zheng, Wen-Xin

    2014-01-01

    Objectives: To characterize the exact individual roles of gonadotropins on ovarian epithelial carcinogenesis, an earlier study showed that prohibitin was significantly up-regulated by luteinizing hormone (LH). To further clarify the role of prohibitin in ovarian carcinogenesis and its association with LH, herein we studied the expression of prohibitin in various ovarian tissues including different developmental stages of ovarian epithelial tumors. Methods: A total of 135 samples were studied by immunohistochemistry. These included benign ovarian cases with follicles, ovarian surface epithelia and ovarian epithelial inclusions (OEI) (n=30), serous cystadenoma (n=14), serous borderline tumor (n=12), serous carcinoma (n=20), mucinous cystadenoma (n=10), mucinous borderline tumor (n=10), mucinous carcinomas (n=10), endometrioid carcinomas (n=12), poorly/undifferentiated carcinomas (n=5), and fallopian tube (n=12). Results: Strong and diffuse staining of prohibitin was detected in luteinized ovarian stromal cells, follicular cells, fallopian tube, and OEI with serous differentiation. A significantly higher prohibitin expression in luteinized stromal cells than in non-luteinized stromal cells was observed (POEI. However, compared to the level of prohibitin expression in OEI, it showed a trend of gradual loss from benign ovarian tumors, to borderline tumors and to carcinomas (POEI. Conclusions: These data further suggest that prohibitin plays a tumor suppressing role, which is probably associated with LH mediated protection role against ovarian epithelial carcinoma. In addition to the tumor suppressive role of prohibitin, it also plays a role in cellular differentiation, which may be helpful to differentiate ovarian mucinous tumors from the tumors with serous differentiation in clinical settings. More importantly, our findings are supportive that the ovarian epithelial cancers, particularly the serous cancers including those precursors with serous differentiation are

  17. Reversal of Adriamycin Resistance by Verapamil in Human Ovarian Cancer

    Science.gov (United States)

    Rogan, Alfred M.; Hamilton, Thomas C.; Young, Robert C.; Klecker, Raymond W.; Ozols, Robert F.

    1984-06-01

    The effectiveness of adriamycin in the treatment of ovarian cancer and other human tumors has been limited by the development of drug resistance. Verapamil, a calcium channel blocking agent, completely reversed adriamycin resistance in human ovarian cancer cells with moderate (three- to sixfold) degrees of resistance and partially reversed resistance in highly (150-fold) resistant cells. The potentiating effect of verapamil was due to inhibition of adriamycin efflux in the resistant cells. These results have led to a clinical trial of adriamycin and verapamil in refractory ovarian cancer patients.

  18. An overview about mitochondrial DNA mutations in ovarian cancer ...

    African Journals Online (AJOL)

    Background: Ovarian tumour is the second most common form of cancer affecting female reproductive system and the most lethal of the gynaecological malignancies. Since past decades, tremendous efforts have been made to illuminate the molecular basis for initiation and progression of ovarian carcinoma. A low quantity ...

  19. Options for modulation of drug resistance in ovarian cancer

    NARCIS (Netherlands)

    Arts, HJG; Van der Zee, AGJ; De Jong, S; De Vries, EGE

    2000-01-01

    The objective of this paper is to present an update of mechanisms responsible for drug resistance in ovarian cancer and the possible therapeutic options to modulate this resistance using literature review with emphasis on data acquired in studies comprising ovarian tumor samples. The classic

  20. [Assessment and impact of intrathoracic disease in advanced ovarian cancer].

    Science.gov (United States)

    Cohen-Mouly, S; Badia, A; Bats, A-S; Barthes, F; Bensaïd, C; Huchon, C; Riquet, M; Lécuru, F

    2010-05-01

    As seventy-five percent of patients with ovarian cancer are diagnosed at an advanced stage (FIGO stage III/IV), optimal surgery is then difficult to perform. The aim of our study is to assess the interest of thoracoscopy in the management of ovarian carcinoma with pleural effusion.

  1. Combination of cancer antigen 125 and carcinoembryonic antigen can improve ovarian cancer diagnosis

    DEFF Research Database (Denmark)

    Sørensen, Sofie Sølvsten; Mosgaard, Berit Jul

    2011-01-01

    The purpose of the present study was to evaluate the ability of the tumour marker carcinoembryonic antigen (CEA) in combination with cancer antigen 125 (CA-125) to differentiate between malignant ovarian and malignant non-ovarian disease.......The purpose of the present study was to evaluate the ability of the tumour marker carcinoembryonic antigen (CEA) in combination with cancer antigen 125 (CA-125) to differentiate between malignant ovarian and malignant non-ovarian disease....

  2. Use of antidepressants and risk of epithelial ovarian cancer

    DEFF Research Database (Denmark)

    Mørch, Lina S; Dehlendorff, Christian; Baandrup, Louise

    2017-01-01

    Antidepressants are widely prescribed among women to treat depression and anxiety disorders, but studies of their effects on gynecological cancer risk are sparse. We assessed associations between various antidepressants and risk of epithelial ovarian cancer. By using Danish nationwide registers, we...... identified all women (cases) aged 30-84 years with incident epithelial (serous, endometrioid, clear cell or mucinous) ovarian cancer during 2000-2011 (n = 4,103) and matched each case to 20 population controls (n = 58,706) by risk-set matching. Data on drug use (including tricyclic and related......-sided 95% confidence intervals (CIs) for epithelial ovarian cancer associated with antidepressive drug use. Compared with non-use, use of selective serotonin reuptake inhibitors was associated with a decreased risk of ovarian cancer (OR, 0.85; 95% CI, 0.74-0.96), whereas the associations for other...

  3. 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

    PURPOSE: 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. METHODS: In a population-based case-control study in Denmark, we included 554 women with invasive ovarian...... cancer, 202 with ovarian borderline tumors, and 1,564 controls aged 35-79 years. The analyses were performed in multiple logistic regression models. RESULTS: We found a significantly increased risk of ovarian borderline tumors among women with a history of PID (OR = 1.50; 95% CI 1.......08-2.08) but no apparent association between PID and risk of invasive ovarian cancer (OR = 0.83; 95% CI 0.65-1.05). We found no effect of age at time of first PID or time since first PID on the risk for either condition. CONCLUSION: Our results suggest that a history of PID is associated with an increased risk of ovarian...

  4. 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.

  5. [Meigs' syndrome caused by bilateral ovarian fibroma mimicking ovarian cancer].

    Science.gov (United States)

    Sánchez-Torres, D A; Díaz-Murillo, R; Kazlauskas, S; de Santiago, J; Zapardiel, I

    2016-02-01

    We report the case of a 55-year-old patient who pre- sented a pelvic mass, ascites and elevated serum CA125. Suspecting a malignant process she underwent surgery and a total hysterectomy with bilateral salpigo-oforectomy was performed. Pathologic report revealed a bilateral ovarian fibroma and non-tumoral ascites. The presence of elevated serum CA125 levels in a postmenopausal woman with a pelvic mass and ascites suggest an ovarian malignant disease. However, in case of Meigs'syndrome, all symptoms will diappear after removal of the pelvic tumor, so a fast surgical management of the patients is mandatory.

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

    OpenAIRE

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

    2016-01-01

    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-...

  7. Multidisciplinary Strategies in the Prevention and Early Detection of Ovarian Cancer

    National Research Council Canada - National Science Library

    Mok, Samuel

    2002-01-01

    Ovarian cancer is the fourth cause of death from all cancers among American women and ranks the highest among deaths from gynecologic malignancies Although the cure rate with stage I ovarian cancer approaches 90...

  8. Research Summaries: The 11th Biennial Rivkin Center Ovarian Cancer Research Symposium.

    Science.gov (United States)

    Armstrong, Deborah K

    2017-11-01

    In September 2016, the 11th biennial ovarian cancer research symposium was presented by the Rivkin Center for Ovarian Cancer and the American Association for Cancer Research. The 2016 symposium focused on 4 broad areas of research: Mechanisms of Initiation and Progression of Ovarian Cancer, Tumor Microenvironment and Models of Ovarian Cancer, Detection and Prevention of Ovarian Cancer, and Novel Therapeutics for Ovarian Cancer. The presentations and abstracts from each of these areas are reviewed in this supplement to the International Journal of Gynecologic Oncology.

  9. Ovarian cancer risk and use of phenolphthalein-containing laxatives.

    Science.gov (United States)

    Cooper, Glinda S; Longnecker, Matthew P; Peters, Ruth K

    2004-01-01

    Experimental studies in rodents demonstrated the carcinogenic potential of phenolphthalein, the active ingredient in some laxatives, administered at doses similar to the dose that could be used by humans. Ovarian cancer was one of the cancers observed in these studies. We examined the association between epithelial ovarian cancer and use of phenolphthalein-containing laxatives in a population-based case-control study. The study includes 356 epithelial ovarian cancer cases (256 invasive, 100 borderline) and 424 controls. Cases were identified through a population-based registry in Los Angeles County in 1992-1998, and controls were matched to cases by age, race/ethnicity and neighborhood. Data on laxative use (specific brands, frequency of use, usual dose) were obtained by structured in-person interview. Compared to women who never used a laxative, ever use of a phenolphthalein-containing laxative was not associated with an increased risk of invasive ovarian cancer (odds ratio (OR) 1.1, 95% confidence interval (CI) 0.75, 1.5) or of borderline ovarian cancer (OR 0.75, 95%CI 0.37, 1.5). Total days used, mean number of pills per day and cumulative dose were also unrelated to risk. This study provides some assurance that phenolphthalein-containing laxatives do not increase the risk of ovarian cancer in humans. These findings are of particular importance to those countries in which phenolphthalein is still used in over-the-counter medications.

  10. 76 FR 55209 - National Ovarian Cancer Awareness Month, 2011

    Science.gov (United States)

    2011-09-07

    ... month, we remember the mothers, sisters, and daughters we have lost to ovarian cancer, and we extend our... the women, families, and professionals working to end this disease. The Centers for Disease Control...

  11. Aurora-A Oncogene in Human Ovarian Cancer

    National Research Council Canada - National Science Library

    Cheng, Jin Q

    2006-01-01

    .... Ectopic expression of Aurora-A renders cells resistant to cisplatin (CDDP), etoposide and paclitaxel-induced apoptosis and stimulates Akt1 and Akt2 activity in wild-type p53 but not p53-null ovarian cancer cells...

  12. Menstrual pain and risk of epithelial ovarian cancer

    DEFF Research Database (Denmark)

    Babic, Ana; Harris, Holly R; Vitonis, Allison F

    2018-01-01

    Menstrual pain, a common gynecological condition, has been associated with increased risk of ovarian cancer in some, but not all studies. Furthermore, potential variations in the association between menstrual pain and ovarian cancer by histologic subtype have not been adequately evaluated due...... to lack of power. We assessed menstrual pain using either direct questions about having experienced menstrual pain, or indirect questions about menstrual pain as indication for use of hormones or medications. We used multivariate logistic regression to calculate the odds ratio (OR) for the association...... between severe menstrual pain and ovarian cancer, adjusting for potential confounders and multinomial logistic regression to calculate ORs for specific histologic subtypes. We observed no association between ovarian cancer and menstrual pain assessed by indirect questions. Among studies using direct...

  13. 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...

  14. 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.

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

    Science.gov (United States)

    ... Inherited risk Hormone replacement therapy Weight and height Endometriosis The following are protective factors for ovarian, fallopian tube, and primary peritoneal cancer: Oral contraceptives Tubal ligation Giving birth Salpingectomy ...

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

    Science.gov (United States)

    ... Inherited risk Hormone replacement therapy Weight and height Endometriosis The following are protective factors for ovarian, fallopian tube, and primary peritoneal cancer: Oral contraceptives Tubal ligation Giving birth Salpingectomy ...

  17. Chronic Recreational Physical Inactivity and Epithelial Ovarian Cancer Risk

    DEFF Research Database (Denmark)

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

    2016-01-01

    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...

  18. 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.

  19. Risk Factors for Invasive Epithelial Ovarian Cancer by Histologic Subtype

    Directory of Open Access Journals (Sweden)

    Quirk JT

    2004-10-01

    Full Text Available It is unclear whether the different histologic subtypes of epithelial ovarian carcinoma have different risk factors. We investigated the relationships between selected epidemiologic variables (i.e., parity, family history of ovarian cancer, oral contraceptive use, a history of tubal ligation and noncontraceptive estrogen use and the major histologic subtypes of epithelial ovarian cancer in a hospital-based case-control study of adult women at Roswell Park Cancer Institute in Buffalo, NY, USA. Multivariate unconditional logistic regression models were used for statistical analysis. We observed a pattern of increased risk associated with family history and a pattern of risk reduction associated with parity, noncontraceptive estrogen use and tubal ligation across all histologic subtype groups. However, we did not observe a consistent pattern of risk associated with oral contraceptive use. These results provide some additional support for the hypothesis that the effects of various ovarian cancer risk factors may differ according to the histologic subtype.

  20. 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...

  1. Obesity and risk of ovarian cancer subtypes

    DEFF Research Database (Denmark)

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

    2013-01-01

    (13 548 cases and 17 913 controls). We combined study-specific adjusted odds ratios (ORs) using a random-effects model. We further examined the associations by histological subtype, menopausal status and post-menopausal hormone use. High BMI (all time-points) was associated with increased risk......-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...

  2. Hormone replacement therapy and survival after surgery for ovarian cancer.

    OpenAIRE

    Eeles, R A; Tan, S; Wiltshaw, E; Fryatt, I; A'Hern, R P; Shepherd, J H; Harmer, C L; Blake, P R; Chilvers, C E

    1991-01-01

    OBJECTIVE--To evaluate whether hormone replacement therapy affects survival in women who have undergone bilateral salphingo-oophorectomy because of epithelial ovarian cancer. DESIGN--Retrospective analysis by review of patients' notes and questionnaires completed by general practitioners to compare the overall survival and disease free survival in patients with ovarian cancer who did or did not receive hormone replacement therapy after diagnosis. Data were analysed by Cox regression, with hor...

  3. Nuclear medicine for imaging of epithelial ovarian cancer.

    Science.gov (United States)

    Abedi, Seyed Mohammad; Mardanshahi, Alireza; Shahhosseini, Roza; Hosseinimehr, Seyed Jalal

    2016-05-01

    Cancer is one of the leading causes of mortality worldwide. Usually, the diagnosis of cancer at an early stage is important to facilitate proper treatment and survival. Nuclear medicine has been successfully used in the diagnosis, staging, therapy and monitoring of cancers. Single-photon emission computed tomography and PET-based companion imaging agents are in development for use as a companion diagnostic tool for patients with ovarian cancer. The present review discusses the basic and clinical studies related to the use of radiopharmaceuticals in the diagnosis and management of ovarian cancer, focusing on their utility and comparing them with other imaging techniques such as computed tomography and MRI.

  4. History of thyroid disease and survival of ovarian cancer patients

    DEFF Research Database (Denmark)

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

    2017-01-01

    BACKGROUND: Findings from in vitro studies suggest that increased exposure to thyroid hormones can influence progression of ovarian tumours. However, epidemiologic evidence on this topic is limited. METHODS: We pooled data from 11 studies from the Ovarian Cancer Association Consortium. Using......=624 cases) and mortality (HR=1.16; 95% CI=1.03-1.31). Neither duration of hypothyroidism nor use of thyroid medications was associated with survival. CONCLUSIONS: In this large study of women with ovarian cancer, we found that recent history of hyperthyroidism and overall history of hypothyroidism...

  5. The Role of MicroRNAs in Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Yasuto Kinose

    2014-01-01

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

  6. 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.

  7. Mismatch repair and treatment resistance in ovarian cancer

    Directory of Open Access Journals (Sweden)

    van der Burg Maria EL

    2006-07-01

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

  8. Mismatch repair and treatment resistance in ovarian cancer

    International Nuclear Information System (INIS)

    Helleman, Jozien; Staveren, Iris L van; Dinjens, Winand NM; Kuijk, Patricia F van; Ritstier, Kirsten; Ewing, Patricia C; Burg, Maria EL van der; Stoter, Gerrit; Berns, Els MJJ

    2006-01-01

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

  9. Safety assessment of ovarian cryopreservation and transplantation in nude mice bearing human epithelial ovarian cancer.

    Science.gov (United States)

    Zhu, Gen-Hai; Wang, Sheng-Tan; Yang, Zhao-Xin; Cai, Jun-Hong; Chen, Chun-Ying; Yao, Mao-Zhong; Hong, Lan; He, Guo-Li; Yang, Shu-Ying

    2012-01-01

    Nude mice with orthotopic transplantation of human ovarian epithelial cancer were used to investigate screening criteria for paraneoplastic normal ovarian tissue and the security of the freezing and thawing for ovarian tissue transplantation. Expression of CK-7, CA125, P53, survivin, MMP-2/TIMP- 2 in paraneoplastic normal ovarian tissues were detected by RT-PCR as well as immunohistochemistry. The tissues of the groups with all negative indicators of RT-PCR, all negative indicators of immunohistochemistry, negative expression of CK-7, CA125 and survivin, positive expression of CK-7, CA125 and survivin, cancer tissues and normal ovarian tissues of nude mice were used for freezing and thawing transplantation, to analyze overt and occult carcinogenesis rates after transplantation. When all indicators or the main indicators, CK-7, CA125 and survivin, were negative, tumorigenesis did not occur after transplantation. In addition the occult carcinogenesis rate was lower than in the group with positive expression of CK-7, CA125 and survivin (Povarian tissues, rates did not change (P>0.05). There was no statistical significance among rates after transplantation of ovarian tissues which were obtained under different severity conditions (P>0.05). Negative expression of CK-7, CA125 and survivin can be treated as screening criteria for security of ovarian tissues for transplantation. Immunohistochemical methods can be used as the primary detection approach. Both subcutaneous and orthotopic transplantation are safe. The initial severity does not affect the carcinogenesis rate after tissue transplantation. Freezing and thawing ovarian tissue transplantation in nude mice with human epithelial ovarian carcinoma is feasible and safe.

  10. 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.

  11. Adjuvant exemestane with ovarian suppression in premenopausal breast cancer.

    Science.gov (United States)

    Pagani, Olivia; Regan, Meredith M; Walley, Barbara A; Fleming, Gini F; Colleoni, Marco; Láng, István; Gomez, Henry L; Tondini, Carlo; Burstein, Harold J; Perez, Edith A; Ciruelos, Eva; Stearns, Vered; Bonnefoi, Hervé R; Martino, Silvana; Geyer, Charles E; Pinotti, Graziella; Puglisi, Fabio; Crivellari, Diana; Ruhstaller, Thomas; Winer, Eric P; Rabaglio-Poretti, Manuela; Maibach, Rudolf; Ruepp, Barbara; Giobbie-Hurder, Anita; Price, Karen N; Bernhard, Jürg; Luo, Weixiu; Ribi, Karin; Viale, Giuseppe; Coates, Alan S; Gelber, Richard D; Goldhirsch, Aron; Francis, Prudence A

    2014-07-10

    Adjuvant therapy with an aromatase inhibitor improves outcomes, as compared with tamoxifen, in postmenopausal women with hormone-receptor-positive breast cancer. In two phase 3 trials, we randomly assigned premenopausal women with hormone-receptor-positive early breast cancer to the aromatase inhibitor exemestane plus ovarian suppression or tamoxifen plus ovarian suppression for a period of 5 years. Suppression of ovarian estrogen production was achieved with the use of the gonadotropin-releasing-hormone agonist triptorelin, oophorectomy, or ovarian irradiation. The primary analysis combined data from 4690 patients in the two trials. After a median follow-up of 68 months, disease-free survival at 5 years was 91.1% in the exemestane-ovarian suppression group and 87.3% in the tamoxifen-ovarian suppression group (hazard ratio for disease recurrence, second invasive cancer, or death, 0.72; 95% confidence interval [CI], 0.60 to 0.85; P<0.001). The rate of freedom from breast cancer at 5 years was 92.8% in the exemestane-ovarian suppression group, as compared with 88.8% in the tamoxifen-ovarian suppression group (hazard ratio for recurrence, 0.66; 95% CI, 0.55 to 0.80; P<0.001). With 194 deaths (4.1% of the patients), overall survival did not differ significantly between the two groups (hazard ratio for death in the exemestane-ovarian suppression group, 1.14; 95% CI, 0.86 to 1.51; P=0.37). Selected adverse events of grade 3 or 4 were reported for 30.6% of the patients in the exemestane-ovarian suppression group and 29.4% of those in the tamoxifen-ovarian suppression group, with profiles similar to those for postmenopausal women. In premenopausal women with hormone-receptor-positive early breast cancer, adjuvant treatment with exemestane plus ovarian suppression, as compared with tamoxifen plus ovarian suppression, significantly reduced recurrence. (Funded by Pfizer and others; TEXT and SOFT ClinicalTrials.gov numbers, NCT00066703 and NCT00066690, respectively.).

  12. Obesity and survival among women with ovarian cancer

    DEFF Research Database (Denmark)

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

    2015-01-01

    women with ovarian carcinoma. We combined study-specific adjusted hazard ratios (HRs) using random-effects models to estimate pooled HRs (pHR). We further explored associations by histologic subtype. RESULTS: Overall, 6715 (54%) deaths occurred during follow-up. A significant OS disadvantage......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 collaborative...... analysis to assess the association between body mass index (BMI), assessed shortly before diagnosis, progression-free survival (PFS), ovarian cancer-specific survival and overall survival (OS) among women with invasive ovarian cancer. METHODS: We used original data from 21 studies, which included 12 390...

  13. Histone Deacetylase Inhibitor Therapy in Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Noriyuki Takai

    2010-01-01

    Full Text Available Since epigenetic alterations are believed to be involved in the repression of tumor suppressor genes and promotion of tumorigenesis in ovarian cancers, novel compounds endowed with a histone deacetylase (HDAC inhibitory activity are an attractive therapeutic approach. In this review, we discuss the biologic and therapeutic effects of HDAC inhibitors (HDACIs in treating ovarian cancer. HDACIs were able to mediate inhibition of cell growth, cell cycle arrest, apoptosis, and expression of genes related to the malignant phenotype in a variety of ovarian cancer cell lines. Furthermore, HDACIs were able to induce the accumulation of acetylated histones in the chromatin of the p21WAF1 gene in human ovarian carcinoma cells. In xenograft models, some of HDACIs have demonstrated antitumor activity with only few side effects. Some clinical trials demonstrate that HDACI drugs provide an important class of new mechanism-based therapeutics for ovarian cancer. In this review, we discuss the biologic and therapeutic effects of HDACIs in treating ovarian cancer, especially focusing on preclinical studies and clinical trials.

  14. Evaluating the ovarian cancer gonadotropin hypothesis: A candidate gene study

    Science.gov (United States)

    Lee, Alice W.; Tyrer, Jonathan P.; Doherty, Jennifer A.; Stram, Douglas A.; Kupryjanczyk, Jolanta; Dansonka-Mieszkowska, Agnieszka; Plisiecka-Halasa, Joanna; Spiewankiewicz, Beata; Myers, Emily J.; Chenevix-Trench, Georgia; Fasching, Peter A.; Beckmann, Matthias W.; Ekici, Arif B.; Hein, Alexander; Vergote, Ignace; Van Nieuwenhuysen, Els; Lambrechts, Diether; Wicklund, Kristine G.; Eilber, Ursula; Wang-Gohrke, Shan; Chang-Claude, Jenny; Rudolph, Anja; Sucheston-Campbell, Lara; Odunsi, Kunle; Moysich, Kirsten B.; Shvetsov, Yurii B.; Thompson, Pamela J.; Goodman, Marc T.; Wilkens, Lynne R.; Dörk, Thilo; Hillemanns, Peter; Dürst, Matthias; Runnebaum, Ingo B.; Bogdanova, Natalia; Pelttari, Liisa M.; Nevanlinna, Heli; Leminen, Arto; Edwards, Robert P.; Kelley, Joseph L.; Harter, Philipp; Schwaab, Ira; Heitz, Florian; du Bois, Andreas; Orsulic, Sandra; Lester, Jenny; Walsh, Christine; Karlan, Beth Y.; Hogdall, Estrid; Kjaer, Susanne K.; Jensen, Allan; Vierkant, Robert A.; Cunningham, Julie M.; Goode, Ellen L.; Fridley, Brooke L.; Southey, Melissa C.; Giles, Graham G.; Bruinsma, Fiona; Wu, Xifeng; Hildebrandt, Michelle A.T.; Lu, Karen; Liang, Dong; Bisogna, Maria; Levine, Douglas A.; Weber, Rachel Palmieri; Schildkraut, Joellen M.; Iversen, Edwin S.; Berchuck, Andrew; Terry, Kathryn L.; Cramer, Daniel W.; Tworoger, Shelley S.; Poole, Elizabeth M.; Olson, Sara H.; Orlow, Irene; Bandera, Elisa V.; Bjorge, Line; Tangen, Ingvild L.; Salvesen, Helga B.; Krakstad, Camilla; Massuger, Leon F.A.G.; Kiemeney, Lambertus A.; Aben, Katja K.H.; van Altena, Anne M.; Bean, Yukie; Pejovic, Tanja; Kellar, Melissa; Le, Nhu D.; Cook, Linda S.; Kelemen, Linda E.; Brooks-Wilson, Angela; Lubinski, Jan; Gronwald, Jacek; Cybulski, Cezary; Jakubowska, Anna; Wentzensen, Nicolas; Brinton, Louise A.; Lissowska, Jolanta; Yang, Hannah; Nedergaard, Lotte; Lundvall, Lene; Hogdall, Claus; Song, Honglin; Campbell, Ian G.; Eccles, Diana; Glasspool, Rosalind; Siddiqui, Nadeem; Carty, Karen; Paul, James; McNeish, Iain A.; Sieh, Weiva; McGuire, Valerie; Rothstein, Joseph H.; Whittemore, Alice S.; McLaughlin, John R.; Risch, Harvey A.; Phelan, Catherine M.; Anton-Culver, Hoda; Ziogas, Argyrios; Menon, Usha; Ramus, Susan J.; Gentry-Maharaj, Aleksandra; Harrington, Patricia; Pike, Malcolm C.; Modugno, Francesmary; Rossing, Mary Anne; Ness, Roberta B.; Pharoah, Paul D.P.; Stram, Daniel O.; Wu, Anna H.; Pearce, Celeste Leigh

    2016-01-01

    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 of how variability in genes involved in the gonadotropin signaling pathway impacts disease risk is warranted. Methods Genetic data from 41 ovarian cancer study sites were pooled and unconditional logistic regression was used to evaluate whether any of the 2185 SNPs from 11 gonadotropin signaling pathway genes was associated with ovarian cancer risk. A burden test using the admixture likelihood (AML) method was also used to evaluate gene-level associations. Results We did not find any genome-wide significant associations between individual SNPs and ovarian cancer risk. However, there was some suggestion of gene-level associations for four gonadotropin signaling pathway genes: INHBB (p = 0.045, mucinous), LHCGR (p = 0.046, high-grade serous), GNRH (p = 0.041, high-grade serous), and FSHB (p = 0.036, overall invasive). There was also suggestive evidence for INHA (p = 0.060, overall invasive). Conclusions Ovarian cancer studies have limited sample numbers, thus fewer genome-wide susceptibility alleles, with only modest associations, have been identified relative to breast and prostate cancers. We have evaluated the majority of ovarian cancer studies with biological samples, to our knowledge, leaving no opportunity for replication. Using both our understanding of biology and powerful gene-level tests, we have identified four putative ovarian cancer loci near INHBB, LHCGR, GNRH, and FSHB that warrant a second look if larger sample sizes and denser genotype chips become available. PMID:25528498

  15. Geranylgeranylacetone inhibits ovarian cancer progression in vitro and in vivo

    International Nuclear Information System (INIS)

    Hashimoto, Kae; Morishige, Ken-ichirou; Sawada, Kenjiro; Ogata, Seiji; Tahara, Masahiro; Shimizu, Shoko; Sakata, Masahiro; Tasaka, Keiichi; Kimura, Tadashi

    2007-01-01

    Geranylgeranylacetone (GGA), an isoprenoid compound, is an anti-ulcer drug developed in Japan. In our previous study, GGA was shown to inhibit ovarian cancer invasion by attenuating Rho activation [K. Hashimoto, K. Morishige, K. Sawada, M. Tahara, S. Shimizu, M. Sakata, K. Tasaka, Y. Murata, Geranylgeranylacetone inhibits lysophosphatidic acid-induced invasion of human ovarian carcinoma cells in vitro. Cancer 103 (2005) 1529-1536.]. In the present study, GGA treatment inhibited ovarian cancer progression in vitro and suppressed the tumor growth and ascites in the in vivo ovarian cancer model. In vitro analysis, treatment of cancer cells by GGA resulted in the inhibition of cancer cell proliferation, the inactivation of Ras, and the suppression of tyrosine phosphorylation of mitogen-activated protein kinase (MAPK). In conclusion, this is the first report that GGA inhibited ovarian cancer progression and the anti-tumor effect by GGA is, at least in part, derived not only from the suppression of Rho activation but also Ras-MAPK activation

  16. Ovarian cancer: Novel molecular aspects for clinical assessment.

    Science.gov (United States)

    Palmirotta, Raffaele; Silvestris, Erica; D'Oronzo, Stella; Cardascia, Angela; Silvestris, Franco

    2017-09-01

    Ovarian cancer is a very heterogeneous tumor which has been traditionally characterized according to the different histological subtypes and differentiation degree. In recent years, innovative molecular screening biotechnologies have allowed to identify further subtypes of this cancer based on gene expression profiles, mutational features, and epigenetic factors. These novel classification systems emphasizing the molecular signatures within the broad spectrum of ovarian cancer have not only allowed a more precise prognostic prediction, but also proper therapeutic strategies for specific subgroups of patients. The bulk of available scientific data and the high refinement of molecular classifications of ovarian cancers can today address the research towards innovative drugs with the adoption of targeted therapies tailored for single molecular profiles leading to a better prediction of therapeutic response. Here, we summarize the current state of knowledge on the molecular bases of ovarian cancer, from the description of its molecular subtypes derived from wide high-throughput analyses to the latest discoveries of the ovarian cancer stem cells. The latest personalized treatment options are also presented with recent advances in using PARP inhibitors, anti-angiogenic, anti-folate receptor and anti-cancer stem cells treatment approaches. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Levels of Distress in Women With a Family History of Ovarian Cancer

    National Research Council Canada - National Science Library

    Kash, Kathryn

    2001-01-01

    ... (mothers, sisters, or daughters). Women will be queried about their objective and subjective risk status, their knowledge of ovarian cancer and risk factors, their uncertainty about ovarian cancer, levels of anxiety and depression...

  18. Levels of Distress in Women With a Family History of Ovarian Cancer

    National Research Council Canada - National Science Library

    Kash, Kathryn

    2005-01-01

    ... (mothers sisters or daughters). Women will be queried about their objective and subjective risk status their knowledge of ovarian cancer and risk factors their uncertainty about ovarian cancer levels of anxiety and depress...

  19. Levels of Distress in Women With a Family History of Ovarian Cancer

    National Research Council Canada - National Science Library

    Kash, Kathryn

    2005-01-01

    The overall goal of this study is to determine the levels of distress in women with a family history of ovarian cancer and to identify the mediating factors between risk of developing ovarian cancer...

  20. 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....

  1. 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...

  2. HLA superfamily assignment is a predictor of immune response to cancer testis antigens and survival in ovarian cancer.

    Science.gov (United States)

    Szender, J Brian; Eng, Kevin H; Matsuzaki, Junko; Miliotto, Anthony; Gnjatic, Sacha; Tsuji, Takemasa; Odunsi, Kunle

    2016-07-01

    To characterize the association between major histocompatibility complex (MHC) types and spontaneous antibody development to the cancer testis (CT) antigen NY-ESO-1. Tumor expression of NY-ESO-1 and serum antibodies to NY-ESO-1 were characterized in addition to human leukocyte antigen (HLA) type for patients with epithelial ovarian cancer. HLA types were assigned to structure-based superfamilies and statistical associations were examined. HLA types were compared to existing reference libraries of HLA frequencies in a European-Caucasian American population. Out of 126 patients identified, 81% were expression positive and 48% had spontaneous antibody responses to NY-ESO-1. There was an association between HLA-B superfamily and seropositivity among patients with tumors expressing NY-ESO-1 (pHLA-B superfamily assignment were driven by HLA-B44. Among all patients, the B27 superfamily was over-represented compared with the general population (pHLA type appears to be associated with spontaneous anti-CT antigen antibodies, as well as with the overall risk of ovarian cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Ovarian Cancer Prevention in High-risk Women.

    Science.gov (United States)

    Temkin, Sarah M; Bergstrom, Jennifer; Samimi, Goli; Minasian, Lori

    2017-12-01

    Ovarian carcinoma is the most lethal malignancy of the female genital tract. Population-based trials in the general population have not demonstrated that screening improves early detection or survival. Therefore, application of prevention strategies is vital to improving outcomes from this disease. Surgical prevention reduces risk and prophylactic risk-reducing salpingo-oophorectomy is the most effective means to prevent ovarian carcinoma in the high-risk patient although the risks do not outweigh the benefits in average risk patients. Other surgical and medical options have unknown or limited efficacy in the high-risk patient. In this review, we define the patient at high risk for ovarian cancer, discuss how to identify these women and weigh their available ovarian cancer prevention strategies.

  4. Primary hepatic embryonal sarcoma masquerading as metastatic ovarian cancer

    Directory of Open Access Journals (Sweden)

    Praseedom Raaj

    2009-06-01

    Full Text Available Abstract Background Hepatic embryonal sarcoma (HES is a rare but aggressive primary tumor of the liver occurring most frequently in childhood. Case presentation We report a case of a 52 year old woman having previously undergone treatment for ovarian serous papillary carcinoma who subsequently presented with a large solitary mass in the liver. Initially this was presumed to be metastasis from the ovarian primary however, on further examination it was shown to be a primary hepatic embryonal sarcoma. Conclusion Primary liver tumors should be considered in differential diagnoses in patients with ovarian cancer who subsequently present with liver tumors. This is particularly important when there is no direct evidence of recurrence of ovarian cancer.

  5. Splenectomy for solitary splenic metastasis of ovarian cancer

    International Nuclear Information System (INIS)

    Koh, Yang Seok; Kim, Jung Chul; Cho, Chol Kyoon

    2004-01-01

    Splenic metastases occur in rare cases with a few case reports of patients in the literature. Generally, splenic metastases mean late dissemination of a disease. Solitary splenic metastases from solid tumors are extremely unusual. We report a case of a patient with ovarian mucinous cystadenocarcinoma who underwent splenectomy for isolated parenchymal metastasis. Ovarian epithelial tumors comprised most of isolated splenic metastases from gynecologic tumor. When isolated splenic recurrence is suspected on image studies and serum tumor markers, intraabdominal gross findings should be examined to exclude peritoneal carcinomatosis. If only spleen was under suspicion of recurrence of ovarian cancer, splenectomy may play a therapeutic role

  6. Sonographic diagnosis of neonatal ovarian cysts: Two cases of spontaneous resolution

    International Nuclear Information System (INIS)

    Nussbaum, A.R.; Sanders, R.C.; Hartman, D.S.; Dudgeon, D.L.; Haller, J.A. Jr.

    1986-01-01

    Sonography established the diagnosis of an ovarian cyst in 12 infants. In two, spontaneous resolution over a 2- to 4-month interval was documented. Six cysts were discovered prenatally and confirmed postnatally, and six were identified in neonates with a palpable abdominal mass or distention. Ten masses were intra-abdominal; two were pelvic in location. The cyst size ranged from 2 to 10 cm in diameter. The cyst was spherical and unilateral in 11 of 12 infants and dumbbell-shaped and bilateral in one infant. Four cysts were anechoic and eight hemorrhagic or torsed cysts were complex or echogenic. In two hemorrhagic cysts a fluid-debris level was detected, and three were septated

  7. The safety of transplanting cryopreserved ovarian tissue in cancer patients

    DEFF Research Database (Denmark)

    Rosendahl, Mikkel; Greve, Tine; Andersen, Claus Yding

    2013-01-01

    Transplantation of frozen/thawed ovarian tissue from patients with a malignant condition is associated with a risk of re-introduction of the disease as the tissue usually is removed before anti-cancer therapy and may thus contain malignant cells. We review studies investigating the presence...... of malignant cells in cryopreserved ovarian tissue from patients with malignant disease and based on the strength of the evidence, recommendations for transplantations are proposed....

  8. 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 self......-reported, pre-diagnosis use of common analgesics and overall/progression-free/disease-specific survival among 7694 women with invasive epithelial ovarian cancer (4273 deaths). RESULTS: Regular analgesic use (at least once per week) was not associated with overall survival (pooled hazard ratios, pHRs (95......% confidence intervals): aspirin 0.96 (0.88-1.04); non-aspirin NSAIDs 0.97 (0.89-1.05); acetaminophen 1.01 (0.93-1.10)), nor with progression-free/disease-specific survival. There was however a survival advantage for users of any NSAIDs in studies clearly defining non-use as less than once per week (pHR=0...

  9. [Nursing care for ovarian cancer patients with intraperitoneal chemotherapy].

    Science.gov (United States)

    Lu, Yu-Ying; Chou, Ju-Fen; Tsao, Lee-Ing; Liang, Shu-Yuan; Wu, Shu-Fang

    2015-02-01

    Ovarian cancer, known as a "silent killer", is the leading cause of gynecologic cancer death. Standard treatments for ovarian cancer are debulking surgery combined with platinum chemotherapy drugs to prolong the survival of patients. According to clinical trials run by the American Society of Gynecologic Oncology, patients who received intraperitoneal (IP) chemotherapy survived longer on average than patients who received intravenous chemotherapy alone. Thus, intraperitoneal chemotherapy is a new potential approach for treating ovarian cancer patients. However, the toxicities and undesirable complications of IP chemotherapy are the major challenges of this treatment approach. This article helps nurses recognize the toxicities and complications of IP chemotherapy and may be used as reference for future revisions to patient care guidelines.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  11. The Contribution of BRCA1 and BRCA2 to Ovarian Cancer

    OpenAIRE

    Ramus, Susan J.; Gayther, Simon A.

    2009-01-01

    Germline mutations of the BRCA1 and BRCA2 genes confer a high life‐time risk of ovarian cancer. They represent the most significant and well characterised genetic risk factors so far identified for the disease. The frequency with which BRCA1/2 mutations occur in families containing multiple cases of ovarian cancer or breast and ovarian cancer, and in population‐based ovarian cancer series varies geographically and between different ethnic groups. There are differences in the frequency of comm...

  12. Targeting the Six1/Eya transcriptional complex for ovarian cancer therapy

    Science.gov (United States)

    2016-09-01

    ELISA assay at 50 µM. ( d ) Representative compounds from class 2-5 inhibit the transcription of the MEF3 reporter (a Six1 target) in a luciferase...is amplified in 15% of epithelial ovarian cancers (EOCs), is overexpressed in as many as 94% of epithelial ovarian cancers, and like Six1, is... amplified in 15% of epithelial ovarian cancers (EOCs), is overexpressed in as many as 94% of epithelial ovarian cancers, and like Six1, is associated with

  13. MTHFR polymorphisms in relation to ovarian cancer risk.

    Science.gov (United States)

    Terry, Kathryn L; Tworoger, Shelley S; Goode, Ellen L; Gates, Margaret A; Titus-Ernstoff, Linda; Kelemen, Linda E; Sellers, Thomas A; Hankinson, Susan E; Cramer, Daniel W

    2010-11-01

    Folate has been hypothesized to influence carcinogenesis due to its dual role in DNA methylation, which regulates gene expression, and synthesis of purine and thymidylate, which is vital for DNA repair. Thus, we examined ovarian cancer risk in relation to two functional polymorphisms (C677T and A1298C) in the MTHFR gene. We genotyped the C677T (rs1801133) and A1298C (rs1801131) MTHFR polymorphisms in 1642 cases and 2068 controls from three studies, the New England Case Control Study (NEC), Nurses' Health Study (NHS), and Mayo Clinic Ovarian Cancer Case Control Study (MAY). Overall, we observed no association between either SNP and ovarian cancer risk (pooled C677T p(trend)=0.59 and A1298C p(trend)=0.58). Significant associations (C677T p(trend)=0.001, A1298C p(trend)=0.02) between these MTHFR SNPs and serous ovarian cancer risk were observed in the NEC study, but were not replicated in the NHS and MAY studies. MTHFR SNPs C677T and A1298C are not associated with ovarian cancer risk. Our results highlight the need for validation of genetic findings. Copyright © 2010 Elsevier Inc. All rights reserved.

  14. 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.

  15. Is there a link between ovarian cancer and tooth agenesis?

    Science.gov (United States)

    Bonds, John; Pollan-White, Sarah; Xiang, Lilin; Mues, Gabriele; D’Souza, Rena

    2014-01-01

    An epidemiologic study from the year 2008 found a highly significant increase of congenital tooth agenesis in women with ovarian cancer suggesting that a common genetic etiology may predispose women to both conditions. The finding was reminiscent of a previously described family harboring an AXIN2 mutation which could be shown to segregate with both the tooth agenesis and the predisposition to colon cancer transmitted in this family. Since tooth agenesis as a marker for susceptibility to ovarian cancer would be of great relevance to both oncologists and women with inborn missing teeth, the relationship between the two disorders requires a thorough assessment. We examined DNA samples from the ovarian cancer patients who participated in the original study, to look for a possible genetic connection between their ovarian malignancies and tooth agenesis. MSX1, PAX9, AXIN2, EDA, WNT10A, BARX and BRCA1 genes were selected for sequence analysis as they may cause tooth agenesis, are expressed in the female reproductive system, and/or are involved in tumorigenesis in general or specifically in the ovary. Our study revealed evidence that one half of the dually affected patients had an independent causation of the two conditions, thus reducing the previously estimated ovarian cancer risk for women with congenital tooth agenesis quite significantly. PMID:24631698

  16. Expression Profiling of Ovarian Cancer: markers and targets for therapy

    NARCIS (Netherlands)

    J. Helleman (Jozien)

    2006-01-01

    textabstractOvarian cancer is the leading cause of death from gynecological cancer in the Western world. The initial response of the primary tumor to taxane and platinum-based chemotherapy is high, however 20% of patients never achieve a clinical response and the majority of the patients will

  17. Difficulty in diagnosis and different prognoses between colorectal cancer with ovarian metastasis and advanced ovarian cancer: An empirical study of different surgical adoptions

    Directory of Open Access Journals (Sweden)

    Ko-Chao Lee

    2017-02-01

    Conclusion: Clinical manifestations of primary CRC with ovarian metastasis may be confused with advanced ovarian cancer. Negative barium enema or colonoscopic exam cannot rule out the possibility of CRC. For patients with a cancer antigen-125 to carcinoembryonic antigen ratio less than 25, 76% are good reference of CRC metastasis to ovaries. Optimal cytoreduction surgery like that used for treating advanced ovarian cancer had a better prognosis than suboptimal cytoreduction colorectal cancer treatment.

  18. Three biomarkers identified from serum proteomic analysis for the detection of early stage ovarian cancer

    NARCIS (Netherlands)

    Bast, R.C.; Yu, Y.H.; Li, J.N.; Sokoll, L.J.; Rai, A.J.; Rosenzweig, J.M.; Cameron, B.; Wang, Y.Y.; Meng, X.Y.; Berchuck, A.; Haaften-Day, C.; Hacker, N.F.; de Bruijn, H.W.A.; van der Zee, A.G.J.; Jacobs, I.J.; Fung, E.T.; Chan, D.W.; Zhang, Z

    Early detection remains the most promising approach to improve long-term survival of patients with ovarian cancer. In a five-center case-control study, serum proteomic expressions were analyzed on 153 patients with invasive epithelial ovarian cancer, 42 with other ovarian cancers, 166 with benign

  19. 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....

  20. Women with spontaneous 46,XX primary ovarian insufficiency (hypergonadotropic hypogonadism) have lower perceived social support than control women

    Science.gov (United States)

    Orshan, Susan A.; Ventura, June L.; Covington, Sharon N.; Vanderhoof, Vien H.; Troendle, James F.; Nelson, Lawrence M.

    2009-01-01

    Objective To test the hypothesis that women with spontaneous primary ovarian insufficiency differ from control women with regard to perceived social support and to investigate the relationship between perceived social support and self-esteem. Design Cross-sectional Setting Mark O. Hatfield Clinical Research Center, National Institutes of Health. Patient(s) Women diagnosed with spontaneous primary ovarian insufficiency (N=154) at a mean age of 27 years and healthy control women (N=63). Intervention(s) Administration of validated self-reporting instruments. Main Outcome Measure(s) Personal Resource Questionnaire-85 (PRQ85), Rosenberg Self-Esteem Scale Result(s) Women with primary ovarian insufficiency had significantly lower scores than controls on the perceived social support scale and the self-esteem scale. The findings remained significant after modeling with multivariate regression for differences in age, marital status, and having children. In patients there was a significant positive correlation between self-esteem scores and perceived social support. We found no significant differences in perceived social support or self-esteem related to marital status, whether or not they had children, or time since diagnosis. Conclusion(s) This evidence supports the need for prospective controlled studies. Strategies to improve social support and self-esteem might provide a therapeutic approach to reduce the emotional suffering that accompanies the life-altering diagnosis of spontaneous primary ovarian insufficiency. PMID:18829005

  1. 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

  2. Bevacizumab-induced transient sixth nerve palsy in ovarian cancer: A case report.

    Science.gov (United States)

    Momeni, Mazdak; Veras, Laura; Zakashansky, Konstantin

    2016-03-01

    We report a case of transient sixth nerve palsy after systemic administration of bevacizumab. Two days after systemic administration of bevacizumab in conjunction with gemcitabine and carboplatin in a 67-year-old woman with recurrent primary ovarian cancer, the patient developed sixth nerve palsy. After bevacizumab was stopped, the complete left sixth nerve palsy resolved spontaneously over the course of 3 months. This is the first reported case of bevacizumab-induced cranial sixth nerve palsy in the treatment of gynecologic malignancy. © 2013 Wiley Publishing Asia Pty Ltd.

  3. 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...... 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...

  4. CLINICAL AND MORPHOLOGICAL FEATURES OF HEREDITARY OVARIAN CANCER

    Directory of Open Access Journals (Sweden)

    K. B. Kotiv

    2017-01-01

    Full Text Available Germ-line mutations in BRCA1 and BRCA2 genes are the most established risk factors for hereditary breast and ovarian cancers. The purpose of the study was to analyze BRCA1/2 testing in ovarian cancer patients. Materials and methods. We analyzed 222 patients with ovarian cancer (OC who underwent genetic testing. Results. Recurrent Slavic mutations in these genes were detected in 60/222 (27% patients.104 patients lacked any clinical signs of hereditary form of the disease, however BRCA1/2 genetic defects were identified among 11 (11% of these women. BRCA1/2-associated carcinomas were characterized by more advanced stage at diagnosis and predominance of high-grade serous histological tumor subtype. Conclusion. These results emphasize the need for BRCA1/2 testing for all patients with OC. BRCA1/2-associated carcinomas have clinical and pathological cgaracteristics, which should be considered while planning therapy. 

  5. Female genital tract tuberculosis presenting as ovarian cancer

    Directory of Open Access Journals (Sweden)

    Malihe Hasanzadeh

    2014-01-01

    Full Text Available Background: Tuberculosis (TB is still a major worldwide concern. There is no pathognomonic clinical feature or imaging findings for definite diagnosis of extra pulmonary TB. Therefore, TB involvement of Gastrointestinal or Genitourinary tract can be easily confused with peritoneal carcinomatosis and advanced ovarian carcinoma. Our aim is to emphasize the importance of considering the disease based upon the epidemiologic clues of the patients, while interpreting the positive results for a suspicious ovarian malignancy. Cases: This paper illustrates 8 cases of ovarian or peritoneal tuberculosis, whose initial diagnoses were malignant processes of the GU tract. Conclusion: Tuberculosis ( TB should be always being considered in the differential diagnosis of advanced ovarian cancer, especially in the regions that are endemic for the disease.

  6. Circulating Prolactin Levels and Risk of Epithelial Ovarian Cancer

    Science.gov (United States)

    Clendenen, Tess V.; Arslan, Alan A.; Lokshin, Anna E.; Liu, Mengling; Lundin, Eva; Koenig, Karen L; Berrino, Franco; Hallmans, Goran; Idahl, Annika; Krogh, Vittorio; Lukanova, Annekatrin; Marrangoni, Adele; Muti, Paola; Nolen, Brian M.; Ohlson, Nina; Shore, Roy E.; Sieri, Sabina; Zeleniuch-Jacquotte, Anne

    2013-01-01

    Purpose Indirect evidence from experimental and epidemiological studies suggests that prolactin may be involved in ovarian cancer development. However, the relationship between circulating prolactin levels and risk of ovarian cancer is unknown. Methods We conducted a nested case-control study of 230 cases and 432 individually-matched controls within three prospective cohorts to evaluate whether pre-diagnostic circulating prolactin is associated with subsequent risk of ovarian cancer. We also assessed whether lifestyle and reproductive factors are associated with circulating prolactin among controls. Results Prolactin levels were significantly lower among post- vs. pre-menopausal women, parous vs. nulliparous women, and past vs. never users of oral contraceptives in our cross-sectional analysis of controls. In our nested case-control study, we observed a non-significant positive association between circulating prolactin and ovarian cancer risk (ORQ4vsQ1: 1.56, 95% CI: 0.94, 2.63, p-trend: 0.15). Our findings were similar in multivariate-adjusted models and in the subgroup of women who donated blood ≥5 years prior to diagnosis. We observed a significant positive association between prolactin and risk for the subgroup of women with BMI ≥25 kg/m2 (ORQ4vsQ1: 3.10, 95% CI: 1.39, 6.90), but not for women with BMI prolactin may be associated with increased risk of ovarian cancer, particularly in overweight/obese women. Factors associated with reduced risk of ovarian cancer, such as parity and use of oral contraceptives, were associated with lower prolactin levels, which suggests that modulation of prolactin may be a mechanism underlying their association with risk. PMID:23378139

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  8. Malignant Bowel Obstruction in Patients With Recurrent Ovarian Cancer.

    Science.gov (United States)

    Tran, Elizabeth; Spiceland, Clayton; Sandhu, Nicole P; Jatoi, Aminah

    2016-04-01

    We sought to report incidence, risk factors, and survival related to bowel obstruction in 311 ovarian cancer patients with recurrent disease. A total of 68 (22%) had a documented bowel obstruction during their cancer course, and 49 (16%) developed it after cancer recurrence. Surprisingly, 142 (45%) fit into an "unknown" category (3+ months of data lacking from last contact/death). No risk factors were identified; management included surgery (n = 21), conservative measures (n = 21), and other (n = 7). Documented bowel obstruction was not associated with a statistically significant reduction in survival after cancer recurrence. In conclusion, although bowel obstruction occurs in only a subgroup of patients with ovarian cancer and does not appear to detract from survival after cancer recurrence, limited end-of-life information may be resulting in an underestimation of incidence. © The Author(s) 2014.

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

    National Research Council Canada - National Science Library

    Hales, Dale B

    2007-01-01

    .... Research in ovarian cancer has been hampered by a lack of suitable animal models. With the exception of the laying hen, no other animal gets ovarian epithelial cancer analogous to the human disease...

  10. Ad-PUMA sensitizes ovarian cancer cells to chemotherapeutic agents.

    Science.gov (United States)

    Luan, Q-C; Sun, Y-R; Han, P; Chen, Y

    2015-12-01

    Ovarian cancer accounted for the first cause of death in female reproductive system tumor even with the operation and chemotherapy. We sought to evaluate the therapeutic potential of p53 up-regulated modulator of apoptosis (PUMA) in ovarian cancer. An adenovirus expressing PUMA (Ad-PUMA), alone or in combination with chemotherapeutic agents, was used to treat two different ovarian cancer cell lines. The mechanism of PUMA-mediated growth suppression and apoptosis was investigated by analysis of caspase-9 activation and the change of mitochondrial membrane potential (Δψm). The exogenous PUMA was expressed 6 h after Ad-PUMA infection, which increased the chemosensitivity of the cancer cells and decreased the IC50 of chemotherapeutic agents compared with uninfected cells. The apoptotic percentage of OVCAR-3 and SKOV3 increased greatly compared with Taxol or Cisplatin alone. There was shear zone in caspase-9 and Δψm decrease after Ad-PUMA infection which suggested apoptosis started in mitochondrial mediated pathway. PUMA plays a role in suppressing tumor growth and sensitizing ovarian cancer cells to anticancer drugs and may be a promising tool for cancer biotherapy.

  11. Regulation and Impact of Cytoplasmic ARID1A in Ovarian Cancer

    Science.gov (United States)

    2016-03-01

    broadly accepted to be a tumor suppressor in an increasing number of cancers, including ovarian . Silencing ARID1A in ovarian surface epithelium...consequence of its tumor suppressor role in chromatin remodeling and transcriptional regulation. We recently used a well annotated ovarian cancer tissue...and advanced stage disease. In ovarian cancer patients whose tumors have loss of nuclear ARID1A with prevalent cytoplasmic ARID1A had a very grave

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    Epithelial ovarian cancer (EOC) is one of the deadliest common cancers. The five most common types of disease are high-grade and low-grade serous, endometrioid, mucinous and clear cell carcinoma. Each of these subtypes present distinct molecular pathogeneses and sensitivities to treatments. Recent...... studies show that certain genetic variants confer susceptibility to all subtypes while other variants are subtype-specific. Here, we perform an extensive analysis of the genetic architecture of EOC subtypes. To this end, we used data of 10,014 invasive EOC patients and 21,233 controls from the Ovarian...

  13. 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. PATIENTS AND METHODS: The study consisted of three parts: Part I: Biomarker data obtained from mass spectrometry, baseline data and, surgical outcome were...... used to construct predictive indices for complete tumour resection; Part II: sera from randomly selected patients from part I were analyzed using enzyme-linked immunosorbent assay (ELISA) to investigate the correlation to mass spectrometry; Part III: the indices from part I were validated in a new.......64. CONCLUSION: Our validated model based on biomarkers was unable to predict surgical outcome for patients with ovarian cancer....

  14. 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, recurrent ovarian cancer. Methods In this randomized, double-blind, phase 3 trial, patients were categorized according to the presence or absence of a germline BRCA mutation (gBRCA cohort and non-gBRCA cohort) and the type of non-gBRCA mutation and were randomly assigned in a 2:1 ratio to receive niraparib...

  15. 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...

  16. The innovation in the morphogenesis and epidemiology of ovarian cancer

    Directory of Open Access Journals (Sweden)

    M. M. Vysotsky

    2012-01-01

    Full Text Available The literature review is dedicated to new data in epidemiology and pathogenesis of ovarian cancer. The authors analyze newly obtained data on dietary habits, BMI, sexual behavior, contraception model, the number of labors as possible risk or influencing factors for ovarian cancer. The possible role of dietary habits and reproductive behavior from neolith to modern time is discussed. Controversies concerning possible role of alcohol intake and tobacco smoking are scrutinized. Newly obtained data on the fallopian tube as a primary site of most pelvic high-grade serous carcinomas are discussed.

  17. Ovarian cancer management. Practice guidelines for nuclear physicians.

    Science.gov (United States)

    Classe, J M; Fontanelli, R; Bischof-Delaloye, A; Chatal, J F

    2004-06-01

    Ovarian cancer is a frequent and severe malignancy. Over 75% of cases are diagnosed at an advanced stage with disease spread beyond the ovaries. Despite the high response rates of initial treatments (i.e.,70-80%), the median progression-free survival of advanced ovarian cancer is 16-22 months, and the 5-year overall survival, 20-30%. The majority of these patients relapse, with metastatic peritoneal spread, unresectable, or drug resistant disease. Our goal was to outline current knowledge about diagnosis, prognostic factors, and treatments, and to dwell on non-nuclear medicine and nuclear-medicine diagnostic procedures.

  18. Values and worries of ovarian cancer patients

    Science.gov (United States)

    Pisu, Maria; Kenzik, Kelly M.; Rim, Sun Hee; Funkhouser, Ellen M.; Bevis, Kerri S.; Alvarez, Ronald D.; Cantuaria, Guilherme; Rocconi, Rodney P.; Martin, Michelle Y.

    2018-01-01

    Introduction Older women with ovarian cancer (OC) are less likely to receive guideline concordant treatment. Differences in values and worries about treatment may explain why. Methods Women with OC in 2013–2015 were surveyed about values and worries at the time of initial treatment. Existing values (11 item, e.g., maintaining quality of life) and worries (12 items, e.g., treatment side effects) scales were adapted based on OC literature. Responses were very/somewhat/a little/not at all important or worried. Principal Component Analyses (PCA) identified groups of values and worries that best explained scales' variation. We examined proportions reporting very/somewhat important/worried on ≥1 item in each component by age (older ≥65 years, younger <65 years). Results Of 170 respondents, 42.3%were older. PCA components for values were: functional well-being (3 survey items, proportion of variance explained [PoVE] 26.3%), length of life and sexual functioning (3 items, PoVE 20.1%), attitudes (3 items, PoVE 14.2%), and not becoming a burden (2 items, PoVE 13.7%). PCA components for worries were: economic (4 items, PoVE 27.2%), uncertainty (6 items, PoVE 26.0%), and family impact (2 items, PoVE 16.3%). Older women were less likely to indicate very/somewhat worried to ≥1 item in the economic (51.4% vs 72.4%, p = 0.006), uncertainty (80.6% vs. 98.0%, p = 0.001), and family impact component (55.6% vs. 70.4%, p = 0.03). No other age differences were found. Conclusions While worry during OC treatment decision-making may differ across age groups, values do not. Research should assess how differences in worry might affect OC medical decision-making for older and younger women. PMID:28888542

  19. Values and worries of ovarian cancer patients.

    Science.gov (United States)

    Pisu, Maria; Kenzik, Kelly M; Rim, Sun Hee; Funkhouser, Ellen M; Bevis, Kerri S; Alvarez, Ronald D; Cantuaria, Guilherme; Rocconi, Rodney P; Martin, Michelle Y

    2017-11-01

    Older women with ovarian cancer (OC) are less likely to receive guideline concordant treatment. Differences in values and worries about treatment may explain why. Women with OC in 2013-2015 were surveyed about values and worries at the time of initial treatment. Existing values (11 item, e.g., maintaining quality of life) and worries (12 items, e.g., treatment side effects) scales were adapted based on OC literature. Responses were very/somewhat/a little/not at all important or worried. Principal Component Analyses (PCA) identified groups of values and worries that best explained scales' variation. We examined proportions reporting very/somewhat important/worried on ≥1 item in each component by age (older ≥65years, younger values were: functional well-being (3 survey items, proportion of variance explained [PoVE] 26.3%), length of life and sexual functioning (3 items, PoVE 20.1%), attitudes (3 items, PoVE 14.2%), and not becoming a burden (2 items, PoVE 13.7%). PCA components for worries were: economic (4 items, PoVE 27.2%), uncertainty (6 items, PoVE 26.0%), and family impact (2 items, PoVE 16.3%). Older women were less likely to indicate very/somewhat worried to ≥1 item in the economic (51.4% vs 72.4%, p=0.006), uncertainty (80.6% vs. 98.0%, p=0.001), and family impact component (55.6% vs. 70.4%, p=0.03). No other age differences were found. While worry during OC treatment decision-making may differ across age groups, values do not. Research should assess how differences in worry might affect OC medical decision-making for older and younger women. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Selective killing of ovarian cancer cells through induction of apoptosis by nonequilibrium atmospheric pressure plasma

    International Nuclear Information System (INIS)

    Iseki, Sachiko; Tanaka, Hiromasa; Kondo, Hiroki; Hori, Masaru; Nakamura, Kae; Hayashi, Moemi; Kajiyama, Hiroaki; Kikkawa, Fumitaka; Kano, Hiroyuki

    2012-01-01

    Two independent ovarian cancer cell lines and fibroblast controls were treated with nonequilibrium atmospheric pressure plasma (NEAPP). Most ovarian cancer cells were detached from the culture dish by continuous plasma treatment to a single spot on the dish. Next, the plasma source was applied over the whole dish using a robot arm. In vitro cell proliferation assays showed that plasma treatments significantly decreased proliferation rates of ovarian cancer cells compared to fibroblast cells. Flow cytometry and western blot analysis showed that plasma treatment of ovarian cancer cells induced apoptosis. NEAPP could be a promising tool for therapy for ovarian cancers.

  1. Coexistence of Ovarian Cancer and Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Kuo-How Huang

    2007-01-01

    Full Text Available Coexistence of ovarian cancer and renal cell carcinoma (RCC is extremely rare. Only one case was diagnosed in a total of 584 patients with RCC from 1982 to 2002 at our hospital. A 58-year-old woman presented with an enlarged girdle length for 3 months. Computed tomography scan showed a right cystic adnexal mass measuring 10 × 10 cm, and another tumor measuring 3 × 2 cm at the right kidney. She underwent debulking surgery and radical nephrectomy. Pathologic examination revealed right ovarian clear-cell carcinoma with peritoneal, omental, and fallopian tube metastasis, and conventional clear-cell renal carcinoma. RCC was strongly positive in epithelial membrane antigen (EMA staining and negative in estrogen receptors (ER, progesterone receptors (PR, 34bE12 (high molecular weight cytokeratin, and vimentin staining. Ovarian clear-cell carcinoma showed weakly positive results in EMA staining and negative results in ER, PR, 34bE12, and vimentin staining. Although chemotherapy was given, the patient died of disseminated ovarian cancer metastasis 20 months after operation. In conclusion, coexistence of RCC and ovarian cancer is rare and the pathogenesis remains to be clarified. [J Formos Med Assoc 2007;106(3 Suppl:S15-S19

  2. Molecular genetic analysis of tumor suppressor genes in ovarian cancer

    International Nuclear Information System (INIS)

    Lee, Je Ho; Park, Sang Yun

    1992-04-01

    To examine the loci of putative tumor suppressor genes in ovarian cancers, we performed the molecular genetic analysis with fresh human ovarian cancers and observed the following data. Frequent allelic losses were observed on chromosomes 4p(42%), 6p(50%), 7p(43%), 8q(31%), 12p(38%), 12q(33%), 16p(33%), 16q(37%), and 19p(34%) in addition to the previously reported 6q, 11p, and 17p in ovarian caroinomas. we have used an additional probe, TCP10 to narrow down the deleted region on chromosome 6q. TCP10 was reported to be mapped to 6q 25-27. Allelic loss was found to be 40% in epithelial ovarian caroinomas. This finding suggests that chromosome 6q 24-27 is one of putative region haboring the tumor suppressor gene of epithelial ovarian cancer (particularly serous type). To examine the association between FAL(Fractional Allelic Loss) and histopathological features, the FAL value on each phenotypically different tumor was calculated as the ratio of the number of allelic losses versus the number of cases informative in each chromosomal arm. The average FALs for each phenotypically different tumor were: serous cystoadenocarcinomas. FAL=0.31 : mucinous 0.12 : and clear cell carcinoma. FAL=0.20. (Author)

  3. Ergosterol peroxide inhibits ovarian cancer cell growth through multiple pathways

    Directory of Open Access Journals (Sweden)

    Tan W

    2017-07-01

    Full Text Available Weiwei Tan,1,* Meihong Pan,1,* Hui Liu,1 Hequn Tian,1 Qing Ye,1 Hongda Liu2 1Department of Traditional Chinese Medicine, Yidu Central Hospital of Weifang, Weifang, Shandong, China; 2Department of General Surgery, Qilu Hospital Affiliated to Shandong University, Jinan, Shandong, China *These authors contributed equally to this work Abstract: Ergosterol peroxide (EP, a sterol derived from medicinal mushrooms, has been reported to exert antitumor activity in several tumor types. However, the role of EP toward ovarian cancer cells has not been investigated. In this study, we analyzed the cytotoxicity of EP in various cell lines representing high-grade serous ovarian cancer and low-grade serous ovarian cancer, respectively. Although EP showed no significant inhibition of the viability of normal ovarian surface epithelial cells, it impaired the proliferation and invasion capacities of tumor cells in a dose-dependent manner. We further figured out key modulators involved in its antitumor effects by quantitative reverse transcription polymerase chain reaction, ELISA, and Western blot. The nuclear β-catenin was down-regulated upon EP treatment, subsequently reducing the Cyclin D1 and c-Myc expression levels. Meanwhile, the protein level of protein tyrosine phosphatase SHP2 was up-regulated in EP treated cells, whereas Src kinase activity was inhibited. Both activation of SHP2 phosphatase and inhibition of Src kinase decreased the phosphorylation level of transducer and activator of STAT3 protein, which was implicated in oncogenesis. On the other hand, EP remarkably inhibited the expression and secretion of VEGF-C, implying its involvement in counteracting tumor angiogenesis. Moreover, EP treatment showed comparable cytotoxic effect with β-catenin knock-down or STAT3 inhibition. Taken together, our results demonstrated that EP showed antitumor effects toward ovarian cancer cells through both β-catenin and STAT3 signaling pathways, making it a

  4. Protein expression levels of carcinoembryonic antigen (CEA) in Danish ovarian cancer patients: from the Danish 'MALOVA'ovarian cancer study

    DEFF Research Database (Denmark)

    Hogdall, E.V.; Christensen, L.; Blaakaer, J.

    2008-01-01

    AIMS: To determine the variation in expression of carcinoembryonic antigen (CEA) in 760 epithelial ovarian tumours from Denmark, and to correlate expression with clinicopathological parameters and prognosis for the disease. METHODS: Using tissue arrays (TA), we analysed CEA expression in tissues...... from 189 women diagnosed with low malignant potential ovarian tumours (LMP, borderline ovarian tumours) and 571 women diagnosed with ovarian cancer (OC). RESULTS: Using 30% as the cut-off level for CEA over-expression, 18% of LMPs and 4% of OCs were positive. A higher proportion of mucinous tumours...... were positive compared with other histological subtypes (pCEA expression in the tumour tissue (p = 0.004). In a Cox survival analysis, which included 569 OC cases subgrouped by stage...

  5. Temsirolimus and Bevacizumab in Treating Patients With Advanced Endometrial, Ovarian, Liver, Carcinoid, or Islet Cell Cancer

    Science.gov (United States)

    2017-07-10

    Adult Hepatocellular Carcinoma; Advanced Adult Hepatocellular Carcinoma; Endometrial Serous Adenocarcinoma; Localized Non-Resectable Adult Liver Carcinoma; Lung Carcinoid Tumor; Malignant Pancreatic Gastrinoma; Malignant Pancreatic Glucagonoma; Malignant Pancreatic Insulinoma; Malignant Pancreatic Somatostatinoma; Metastatic Digestive System Neuroendocrine Tumor G1; Ovarian Carcinosarcoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Surface Papillary Adenocarcinoma; Pancreatic Alpha Cell Adenoma; Pancreatic Beta Cell Adenoma; Pancreatic Delta Cell Adenoma; Pancreatic G-Cell Adenoma; Pancreatic Polypeptide Tumor; Recurrent Adult Liver Carcinoma; Recurrent Digestive System Neuroendocrine Tumor G1; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Pancreatic Neuroendocrine Carcinoma; Recurrent Primary Peritoneal Carcinoma; Recurrent Uterine Corpus Carcinoma; Regional Digestive System Neuroendocrine Tumor G1; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIA Uterine Corpus Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIB Uterine Corpus Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IIIC Uterine Corpus Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer; Uterine Carcinosarcoma

  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. Isoliquiritigenin Induces Autophagy and Inhibits Ovarian Cancer Cell Growth

    Directory of Open Access Journals (Sweden)

    Hsin-Yuan Chen

    2017-09-01

    Full Text Available Ovarian cancer is one of the commonest gynecologic malignancies, which has a poor prognosis for patients at the advanced stage. Isoliquiritigenin (ISL, an active flavonoid component of the licorice plant, previously demonstrated antioxidant, anti-inflammatory, and tumor suppressive effects. In this study, we investigated the antitumor effect of ISL on human ovarian cancer in vitro using the human ovarian cancer cell lines, OVCAR5 and ES-2, as model systems. Our results show that ISL significantly inhibited the viability of cancer cells in a concentration- and time-dependent manner. Flow cytometry analysis indicated that ISL induced G2/M phase arrest. Furthermore, the expression of cleaved PARP, cleaved caspase-3, Bax/Bcl-2 ratio, LC3B-II, and Beclin-1 levels were increased in western blot analysis. To clarify the role of autophagy and apoptosis in the effect of ISL, we used the autophagy inhibitor—3-methyladenine (3-MA to attenuate the punctate fluorescence staining pattern of the p62/sequestosome 1 (SQSTM1, red fluorescence and LC3 (green fluorescence proteins after ISL treatment, and 3-MA inhibited the cytotoxicity of ISL. These findings provide new information about the link between ISL-induced autophagy and apoptosis and suggest that ISL is a candidate agent for the treatment of human ovarian cancer.

  8. Coffee, tea, colas, and risk of epithelial ovarian cancer.

    Science.gov (United States)

    Song, Yoon Ju; Kristal, Alan R; Wicklund, Kristine G; Cushing-Haugen, Kara L; Rossing, Mary Anne

    2008-03-01

    Associations of coffee, tea, and other caffeinated beverages with ovarian cancer risk remain uncertain. In a population-based study in Washington State, 781 women with epithelial ovarian cancer diagnosed in 2002 to 2005 and 1,263 controls completed self-administered questionnaires detailing consumption of caffeinated and noncaffeinated coffee, teas, and colas and in-person interviews regarding reproductive and hormonal exposures. We assessed risk associated with coffee, tea, and cola drinking and with total caffeine consumption using logistic regression to calculate odds ratios and 95% confidence intervals. Neither caffeinated nor decaffeinated coffees were associated with ovarian cancer risk; also, we observed no association of total caffeine with risk using a combined index that summed intake from coffee, tea, and carbonated soft drinks. Among teas, neither herbal/decaffeinated nor black teas were associated with risk; however, women who reported drinking >or=1 cup/d of green tea had a 54% reduction in risk (P trend = 0.01). Associations of green tea with risk were similar when invasive and borderline cases were considered separately and when Asian women were excluded from analysis. Green tea, which is commonly consumed in countries with low ovarian cancer incidence, should be further investigated for its cancer prevention properties.

  9. Endometriosis and risks for ovarian, endometrial and breast cancers

    DEFF Research Database (Denmark)

    Mogensen, Julie Brøchner; Kjær, Susanne K.; Mellemkjær, Lene

    2016-01-01

    Objective A growing body of evidence suggests that endometriosis increases the risk for ovarian cancer, but it is less well studied whether the excess risk is confined to certain histotypes. Furthermore, it is not fully resolved if endometriosis is associated with endometrial- and breast cancer....... The aim was to study overall- and histotype-specific risks for these hormone-dependent cancers in women with endometriosis. Methods In the Danish National Patient Register, we identified 45,790 women with a clinical diagnosis of endometriosis during 1977–2012. We linked the cohort to the Danish Cancer...... Register and calculated standardized incidence ratios (SIRs) with corresponding 95% confidence intervals (CIs). Results Endometriosis was associated with increased risks for ovarian cancer (SIR 1.34; 95% CI: 1.16–1.55), due primarily to endometrioid (SIR 1.64; 95% CI: 1.09–2.37) and clear-cell types (SIR 3...

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

    Science.gov (United States)

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

    2012-01-01

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

  11. A 2-stage ovarian cancer screening strategy using the Risk of Ovarian Cancer Algorithm (ROCA) identifies early-stage incident cancers and demonstrates high positive predictive value.

    Science.gov (United States)

    Lu, Karen H; Skates, Steven; Hernandez, Mary A; Bedi, Deepak; Bevers, Therese; Leeds, Leroy; Moore, Richard; Granai, Cornelius; Harris, Steven; Newland, William; Adeyinka, Olasunkanmi; Geffen, Jeremy; Deavers, Michael T; Sun, Charlotte C; Horick, Nora; Fritsche, Herbert; Bast, Robert C

    2013-10-01

    A 2-stage ovarian cancer screening strategy was evaluated that incorporates change of carbohydrate antigen 125 (CA125) levels over time and age to estimate risk of ovarian cancer. Women with high-risk scores were referred for transvaginal ultrasound (TVS). A single-arm, prospective study of postmenopausal women was conducted. Participants underwent an annual CA125 blood test. Based on the Risk of Ovarian Cancer Algorithm (ROCA) result, women were triaged to next annual CA125 test (low risk), repeat CA125 test in 3 months (intermediate risk), or TVS and referral to a gynecologic oncologist (high risk). A total of 4051 women participated over 11 years. The average annual rate of referral to a CA125 test in 3 months was 5.8%, and the average annual referral rate to TVS and review by a gynecologic oncologist was 0.9%. Ten women underwent surgery on the basis of TVS, with 4 invasive ovarian cancers (1 with stage IA disease, 2 with stage IC disease, and 1 with stage IIB disease), 2 ovarian tumors of low malignant potential (both stage IA), 1 endometrial cancer (stage I), and 3 benign ovarian tumors, providing a positive predictive value of 40% (95% confidence interval = 12.2%, 73.8%) for detecting invasive ovarian cancer. The specificity was 99.9% (95% confidence interval = 99.7%, 100%). All 4 women with invasive ovarian cancer were enrolled in the study for at least 3 years with low-risk annual CA125 test values prior to rising CA125 levels. ROCA followed by TVS demonstrated excellent specificity and positive predictive value in a population of US women at average risk for ovarian cancer. Copyright © 2013 American Cancer Society.

  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. Serum angiopoietin-2 and soluble VEGFR-2 levels predict malignancy of ovarian neoplasm and poor prognosis in epithelial ovarian cancer.

    Science.gov (United States)

    Sallinen, Hanna; Heikura, Tommi; Koponen, Jonna; Kosma, Veli-Matti; Heinonen, Seppo; Ylä-Herttuala, Seppo; Anttila, Maarit

    2014-09-23

    The aim of the study was to explore the serum levels of eight angiogenesis biomarkers in patients with benign, borderline or malignant epithelial ovarian neoplasms and to compare them to those of healthy controls. In addition, we aimed to study how those biomarkers predict the clinical course and survival of patients with epithelial ovarian cancer. We enrolled 132 patients with ovarian neoplasms and 32 unaffected women in this study. Serum samples were collected preoperatively at the time of diagnosis and the levels of angiogenesis biomarkers were measured with an ELISA. Levels of Ang-1, Ang-2, VEGF, VEGF-D, VEGF/sVEGFR-2 and Ang-2/ sVEGFR-2 ratios were elevated whereas sVEGFR-2 was lower in patients with ovarian carcinoma than in women with normal ovaries, benign and/or borderline ovarian neoplasms. In ROC analysis, the area under the curve for serum Ang-2/sVEGFR-2 ratio (0.76) was greater than Ang-2 (0.75) and VEGF (0.65) but lower than for CA 125 (0.90) to differentiate ovarian cancer from benign or borderline ovarian tumors. In ovarian cancer high Ang-2/sVEGFR-2 ratio was associated with the presence of ascites, high stage and grade of ovarian cancer, with the size of primary residual tumor>1 cm and with recurrence of disease. Elevated Ang-2, VEGF, VEGF/sVEGFR-2, Ang-2/VEGF and Ang-2/sVEGFR-2 ratios and low level of sVEGFR-2 were significant predictors of poor overall survival (OS) and recurrence free survival (RFS) in univariate survival analyses. Ovarian cancer patients had elevated levels of angiogenesis related growth factors in circulation reflecting increased angiogenesis and poor prognosis. The serum level of Ang-2 predicted most accurately poor OS and Ang-2/sVEGFR-2 ratio malignancy of ovarian neoplasms and short RFS.

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

    International Nuclear Information System (INIS)

    Kim, Ki Hyung; Kang, Yun-Jeong; Jo, Jin-Ok; Ock, Mee Sun; Moon, Soo Hyun; Suh, Dong Soo; Yoon, Man Soo; Park, Eun-Sil; Jeong, Namkung; Eo, Wan-Kyu; Kim, Heung Yeol; Cha, Hee-Jae

    2014-01-01

    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. 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.

  16. 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)

    2017-05-03

    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

  17. Use of antidepressants and risk of epithelial ovarian cancer.

    Science.gov (United States)

    Mørch, Lina S; Dehlendorff, Christian; Baandrup, Louise; Friis, Søren; Kjaer, Susanne K

    2017-12-01

    Antidepressants are widely prescribed among women to treat depression and anxiety disorders, but studies of their effects on gynecological cancer risk are sparse. We assessed associations between various antidepressants and risk of epithelial ovarian cancer. By using Danish nationwide registers, we identified all women (cases) aged 30-84 years with incident epithelial (serous, endometrioid, clear cell or mucinous) ovarian cancer during 2000-2011 (n = 4,103) and matched each case to 20 population controls (n = 58,706) by risk-set matching. Data on drug use (including tricyclic and related antidepressants, selective serotonin reuptake inhibitors, other antidepressants, and potential confounder drugs), medical and reproductive history and socioeconomic parameters, were obtained from nationwide registries. We used conditional logistic regression models to estimate adjusted odds ratios (ORs) and two-sided 95% confidence intervals (CIs) for epithelial ovarian cancer associated with antidepressive drug use. Compared with non-use, use of selective serotonin reuptake inhibitors was associated with a decreased risk of ovarian cancer (OR, 0.85; 95% CI, 0.74-0.96), whereas the associations for other antidepressants were close to unity [tricyclic and related antidepressants: OR, 0.99 (95% CI, 0.78-1.26); other antidepressants: OR, 1.05 (95% CI, 0.76-1.46)]. For individual types of SSRI, reduced ORs were observed for citalopram OR, 0.78 (95% CI, 0.66-0.93), paroxetine 0.79 (95% CI, 0.56-1.12) and sertraline 0.80 (95% CI, 0.60-1.08). Among postmenopausal women, the inverse association was restricted to users of menopausal hormone therapy. In conclusion, use of selective serotonin reuptake inhibitors was associated with a decreased risk of epithelial ovarian cancer; thereby implying potential chemopreventive properties of these drugs. © 2017 UICC.

  18. Reproductive and hormonal factors in association with ovarian cancer in the Netherlands cohort study

    NARCIS (Netherlands)

    Braem, M.G.M.; Onland-Moret, N.C.; Brandt, P.A. van den; Goldbohm, R.A.; Peeters, P.H.M.; Kruitwagen, R.F.P.M.; Schouten, L.J.

    2010-01-01

    Parity, oral contraceptive use, and hysterectomy are known to protect against ovarian cancer, whereas the effect of other reproductive factors remains unclear. The authors investigated the association between several reproductive and hormonal factors and the risk of epithelial invasive ovarian

  19. Evaluating the ovarian cancer gonadotropin hypothesis: A candidate gene study

    NARCIS (Netherlands)

    Lee, A.W.; Tyrer, J.P.; Doherty, J.A.; Stram, D.A.; Kupryjanczyk, J.; Dansonka-Mieszkowska, A.; Plisiecka-Halasa, J.; Spiewankiewicz, B.; Myers, E.J.; Study, G.; Chenevix-Trench, G.; Fasching, P.A.; Beckmann, M.W.; Ekici, A.B.; Hein, A.; Vergote, I.; Nieuwenhuysen, E. Van; Lambrechts, D.; Wicklund, K.G.; Eilber, U.; Wang-Gohrke, S.; Chang-Claude, J.; Rudolph, A.; Sucheston-Campbell, L.; Odunsi, K.; Moysich, K.B.; Shvetsov, Y.B.; Thompson, P.J.; Goodman, M.T.; Wilkens, L.R.; Dork, T.; Hillemanns, P.; Durst, M.; Runnebaum, I.B.; Bogdanova, N.; Pelttari, L.M.; Nevanlinna, H.; Leminen, A.; Edwards, R.P.; Kelley, J.L.; Harter, P.; Schwaab, I.; Heitz, F.; Bois, A. du; Orsulic, S.; Lester, J.; Walsh, C.; Karlan, B.Y.; Hogdall, E.; Kjaer, S.K.; Jensen, A.; Vierkant, R.A.; Cunningham, J.M.; Goode, E.L.; Fridley, B.L.; Southey, M.C.; Giles, G.G.; Bruinsma, F.; Wu, X.; Hildebrandt, M.A.T.; Lu, K.; Liang, D.; Bisogna, M.; Levine, D.A.; Weber, R.P.; Schildkraut, J.M.; Iversen, E.S.; Berchuck, A.; Terry, K.L.; Cramer, D.W; Tworoger, S.S.; Poole, E.M.; Olson, S.H.; Orlow, I.; Bandera, E.V.; Bjorge, L.; Tangen, I.L.; Salvesen, H.B.; Krakstad, C.; Massuger, L.F.A.G.; Kiemeney, L.A.L.M.; Aben, K.K.H.; Altena, A.M. van; Bean, Y.; Pejovic, T.; Kellar, M.; Le, N.D.; Cook, L.S.; Kelemen, L.E.; Brooks-Wilson, A.; Lubinski, J.; Gronwald, J.; Cybulski, C.; Jakubowska, A.; Wentzensen, N.; Brinton, L.A.; Lissowska, J.; Yang, H.; Nedergaard, L.; et al.,

    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 of

  20. The role of the fallopian tube in ovarian cancer.

    Science.gov (United States)

    Tone, Alicia A; Salvador, Shannon; Finlayson, Sarah J; Tinker, Anna V; Kwon, Janice S; Lee, Cheng-Han; Cohen, Trevor; Ehlen, Tom; Lee, Marette; Carey, Mark S; Heywood, Mark; Pike, Judith; Hoskins, Paul J; Stuart, Gavin C; Swenerton, Kenneth D; Huntsman, David G; Gilks, C Blake; Miller, Dianne M; McAlpine, Jessica N

    2012-05-01

    High-grade serous carcinoma (HGSC) is the most common and lethal subtype of ovarian cancer. Research over the past decade has strongly suggested that "ovarian" HGSC arises in the epithelium of the distal fallopian tube, with serous tubal intraepithelial carcinomas (STICs) being detected in 5-10% of BRCA1/2 mutation carriers undergoing risk-reducing surgery and up to 60% of unselected women with pelvic HGSC. The natural history, clinical significance, and prevalence of STICs in the general population (ie, women without cancer and not at an increased genetic risk) are incompletely understood, but anecdotal evidence suggests that these lesions have the ability to shed cells with metastatic potential into the peritoneal cavity very early on. Removal of the fallopian tube (salpingectomy) in both the average and high-risk populations could therefore prevent HGSC, by eliminating the site of initiation and interrupting spread of potentially cancerous cells to the ovarian/peritoneal surfaces. Salpingectomy may also reduce the incidence of the 2 next most common subtypes, endometrioid and clear cell carcinoma, by blocking the passageway linking the lower genital tract to the peritoneal cavity that enables ascension of endometrium and factors that induce local inflammation. The implementation of salpingectomy therefore promises to significantly impact ovarian cancer incidence and outcomes.

  1. Quality of pathology reports for advanced ovarian cancer

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  2. 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

  3. 78 FR 54741 - National Ovarian Cancer Awareness Month, 2013

    Science.gov (United States)

    2013-09-06

    ... options, protections, and benefits. Thanks to this law, insurance companies can no longer set lifetime dollar limits on coverage or cancel coverage because of errors on paperwork. By 2014, the health care law... understanding of ovarian cancer and develop better methods for diagnosis and treatment. As we continue to...

  4. Incidence, Pattern and Management of Ovarian Cancer at a Tertiary ...

    African Journals Online (AJOL)

    Department of Obstetrics and Gynecology, University of Nigeria Teaching Hospital, Ituku‑Ozalla 1Department of. Histopathology, University of ... ovarian cancer giving an incidence rate of 1/405 gynecological admissions per year or 0.3% (95% .... not found in the records. Follow up of patients was by clinical examination and.

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

    Science.gov (United States)

    2014-10-01

    Crown -Crisp scale; depression based on presence of depressive symptoms (from the Mental Health Index), use of anti-depressants, or report of...analysis of phobic anxiety and ovarian cancer risk have been submitted to Psycho-Oncology, and provisionally accepted for a special issue on the

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-12-15

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

  7. Identifying Determinants of PARP Inhibitor Sensitivity in Ovarian Cancer

    Science.gov (United States)

    2017-10-01

    inhibitor selection pressure results in genetic adaptations that enable cells to utilize severely truncated BRCA1 proteins for RAD51 loading and HR repair...Milestone(s) Achieved: Biomarkers are ready for application in clinical trials of BRCA1 mutant ovarian cancer and data is published in peer -reviewed

  8. Ovarian hyperstimulation syndrome followed by ovarian torsion in premenopausal patient using adjuvant tamoxifen treatment for breast cancer

    Directory of Open Access Journals (Sweden)

    Behnaz Moradi

    2016-09-01

    Full Text Available Tamoxifen is a popular medication used in the adjuvant therapy of hormone sensitive breast cancer. In this case report we describe a 39 years old woman presented with ovarian hyperstimulation on the underlying thamoxifen treatment and consecutive ovarian torsion.

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

    Science.gov (United States)

    Jönsson, Jenny-Maria; Johansson, Ida; Dominguez-Valentin, Mev; Kimbung, Siker; Jönsson, Mats; Bonde, Jesper Hansen; Kannisto, Päivi; Måsbäck, Anna; Malander, Susanne; Nilbert, Mef; Hedenfalk, Ingrid

    2014-01-01

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

  10. Intake of dietary flavonoids and risk of epithelial ovarian cancer.

    Science.gov (United States)

    Cassidy, Aedín; Huang, Tianyi; Rice, Megan S; Rimm, Eric B; Tworoger, Shelley S

    2014-11-01

    The impact of different dietary flavonoid subclasses on risk of epithelial ovarian cancer is unclear, with limited previous studies that have focused on only a few compounds. We prospectively examined associations between habitual flavonoid subclass intake and risk of ovarian cancer. We followed 171,940 Nurses' Health Study and Nurses' Health Study II participants to examine associations between intakes of total flavonoids and their subclasses (flavanones, flavonols, anthocyanins, flavan-3-ols, flavones, and polymeric flavonoids) and risk of ovarian cancer by using Cox proportional hazards models. Intake was calculated from validated food-frequency questionnaires collected every 4 y. During 16-22 y of follow-up, 723 cases of ovarian cancer were confirmed through medical records. In pooled multivariate-adjusted analyses, total flavonoids were not statistically significantly associated with ovarian cancer risk (HR for the top compared with the bottom quintile: 0.85; 95% CI: 0.66, 1.09; P-trend = 0.17). However, participants in the highest quintiles of flavonol and flavanone intakes had modestly lower risk of ovarian cancer than did participants in the lowest quintile, although the P-trend was not significant [HRs: 0.76 (95% CI: 0.59, 0.98; P-trend = 0.11) and 0.79 (95% CI: 0.63,1.00; P-trend = 0.26), respectively]. The association for flavanone intake was stronger for serous invasive and poorly differentiated tumors (comparable HR: 0.68; 95% CI: 0.50, 0.92; P-heterogeneity = 0.10, P-trend = 0.07) compared with nonserous and less-aggressive tumors. Intakes of other subclasses were not significantly associated with risk. In food-based analyses used to compare subjects who consumed >1 and ≤ 1 cup black tea/d, the HR was 0.68 (95% CI: 0.51, 0.90; P intakes of flavonols and flavanones as well as black tea consumption may be associated with lower risk of ovarian cancer. Additional prospective studies are required to confirm these findings.

  11. 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. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. 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

    Objective 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. Methods 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. Results 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. Conclusions 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. PMID:28448592

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  14. 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...

  15. 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.; et al.,

    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

  16. 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...

  17. 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.

  18. 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.

  19. Erlotinib Plus Carboplatin and Paclitaxel in Ovarian Carcinoma

    Science.gov (United States)

    2015-10-29

    Brenner Tumor; Fallopian Tube Cancer; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Undifferentiated Adenocarcinoma; Stage III Ovarian Epithelial Cancer; Stage IV Ovarian Epithelial Cancer

  20. The role of surgery in advanced epithelial ovarian cancer.

    Science.gov (United States)

    Martín-Cameán, María; Delgado-Sánchez, Elsa; Piñera, Antonio; Diestro, Maria Dolores; De Santiago, Javier; Zapardiel, Ignacio

    2016-01-01

    Nowadays, the standard management of advanced epithelial ovarian cancer is correct surgical staging and optimal tumour cytoreduction followed by platinum and taxane-based chemotherapy. Standard surgical staging consists of peritoneal washings, total hysterectomy, and bilateral salpingo-oophorectomy, inspection of all abdominal organs and the peritoneal surface, biopsies of suspicious areas or randomised biopsies if they are not present, omentectomy and para-aortic lymphadenectomy. After this complete surgical staging, the International Federation of Gynaecology and Obstetrics (FIGO) staging system for ovarian cancer is applied to determine the management and prognosis of the patient. Complete tumour cytoreduction has shown an improvement in survival. There are some criteria to predict cytoreduction outcomes based on serum biomarkers levels, preoperative imaging techniques, and laparoscopic-based scores. Optimised patient selection for primary cytoreduction would determine patients who could benefit from an optimal cytoreduction and might benefit from interval surgery. The administration of intraperitoneal chemotherapy after debulking surgery has shown an increase in progression-free survival and overall survival, especially in patients with no residual disease after surgery. It is considered that 3-17% of all epithelial ovarian carcinoma (EOC) occur in young women that have not fulfilled their reproductive desires. In these patients, fertility-sparing surgery is a worthy option in early ovarian cancer.

  1. 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.

  2. No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer

    DEFF Research Database (Denmark)

    Hollestelle, Antoinette; van der Baan, Frederieke H; Berchuck, Andrew

    2015-01-01

    ,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). RESULTS: We found no association with risk of ovarian cancer (OR=0...

  3. Recent Advances in Understanding, Diagnosing, and Treating Ovarian Cancer [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Kathryn Mills

    2017-01-01

    Full Text Available Ovarian cancer, a term that encompasses ovarian, fallopian, and peritoneal cancers, is the leading cause of gynecologic cancer mortality. To improve patient outcomes, the field is currently focused on defining the mechanisms of cancer formation and spread, early diagnosis and prevention, and developing novel therapeutic options. This review summarizes recent advances in these areas.

  4. 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.

  5. 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

  6. Dysregulation of mitotic machinery genes precedes genome instability during spontaneous pre-malignant transformation of mouse ovarian surface epithelial cells

    Directory of Open Access Journals (Sweden)

    Ulises Urzúa

    2016-10-01

    Full Text Available Abstract Background Based in epidemiological evidence, repetitive ovulation has been proposed to play a role in the origin of ovarian cancer by inducing an aberrant wound rupture-repair process of the ovarian surface epithelium (OSE. Accordingly, long term cultures of isolated OSE cells undergo in vitro spontaneous transformation thus developing tumorigenic capacity upon extensive subcultivation. In this work, C57BL/6 mouse OSE (MOSE cells were cultured up to passage 28 and their RNA and DNA copy number profiles obtained at passages 2, 5, 7, 10, 14, 18, 23, 25 and 28 by means of DNA microarrays. Gene ontology, pathway and network analyses were focused in passages earlier than 20, which is a hallmark of malignancy in this model. Results At passage 14, 101 genes were up-regulated in absence of significant DNA copy number changes. Among these, the top-3 enriched functions (>30 fold, adj p < 0.05 comprised 7 genes coding for centralspindlin, chromosome passenger and minichromosome maintenance protein complexes. The genes Ccnb1 (Cyclin B1, Birc5 (Survivin, Nusap1 and Kif23 were the most recurrent in over a dozen GO terms related to the mitotic process. On the other hand, Pten plus the large non-coding RNAs Malat1 and Neat1 were among the 80 down-regulated genes with mRNA processing, nuclear bodies, ER-stress response and tumor suppression as relevant terms. Interestingly, the earliest discrete segmental aneuploidies arose by passage 18 in chromosomes 7, 10, 11, 13, 15, 17 and 19. By passage 23, when MOSE cells express the malignant phenotype, the dysregulated gene expression repertoire expanded, DNA imbalances enlarged in size and covered additional loci. Conclusion Prior to early aneuploidies, overexpression of genes coding for the mitotic apparatus in passage-14 pre-malignant MOSE cells indicate an increased proliferation rate suggestive of replicative stress. Concomitant down-regulation of nuclear bodies and RNA processing related genes

  7. PIK3CA alterations in Middle Eastern ovarian cancers

    Directory of Open Access Journals (Sweden)

    Uddin Shahab

    2009-07-01

    Full Text Available Abstract Background PI3K/AKTsignaling pathway plays an important role in cell growth, proliferation, and tumorgenesis of various malignancies. This signaling pathway has been shown to be frequently altered in several human cancers including ovarian cancers. However the role of this oncogenic signaling pathway has not been explored in the Middle Eastern epithelial ovarian cancer (EOC. Therefore, we investigated PI3K/AKT genetic alterations such as PIK3CA amplification, PIK3CA mutation, PTEN protein loss and their relationships with various clinicopathological characteristics in 156 EOCs. Results Fluorescence in situ hybridization (FISH technique and DNA sequencing were used to analyze PIK3CA amplification and mutation respectively. Expression of PIK3CA protein expression (p110 α, PTEN, p-AKT and Ki-67 was analyzed by immunohistochemistry. PIK3CA amplification was seen in 54 of 152 (35.5% EOC cases analyzed; PIK3CA gene mutations in 6/153 EOC (3.9%; KRAS mutations in 3/154 EOC (1.9%, BRAF mutations in 3/156 EOC (1.9%, p53 mutation in 50/154 EOC (32.5%, and loss of PTEN protein expression in 33/144 EOC (22.9%. p110 α overexpression was associated with increased phosphorylation of AKT-Ser 473 and with the proliferation marker Ki-67. Conclusion Our data showed mutual exclusivity between the molecular event of PIK3CA amplification and mutations in PIK3CA, KRAS, BRAF genes, which suggests that each of these alterations may individually be sufficient to drive ovarian tumor pathogenesis independently. High prevalence of genetic alterations in PI3K/AKT pathway in a Middle Eastern ovarian carcinoma provides genetic evidence supporting the notion that dysregulated PI3K/AKT pathways play an important role in the pathogenesis of ovarian cancers.

  8. 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.

  9. Ergosterol peroxide inhibits ovarian cancer cell growth through multiple pathways.

    Science.gov (United States)

    Tan, Weiwei; Pan, Meihong; Liu, Hui; Tian, Hequn; Ye, Qing; Liu, Hongda

    2017-01-01

    Ergosterol peroxide (EP), a sterol derived from medicinal mushrooms, has been reported to exert antitumor activity in several tumor types. However, the role of EP toward ovarian cancer cells has not been investigated. In this study, we analyzed the cytotoxicity of EP in various cell lines representing high-grade serous ovarian cancer and low-grade serous ovarian cancer, respectively. Although EP showed no significant inhibition of the viability of normal ovarian surface epithelial cells, it impaired the proliferation and invasion capacities of tumor cells in a dose-dependent manner. We further figured out key modulators involved in its antitumor effects by quantitative reverse transcription polymerase chain reaction, ELISA, and Western blot. The nuclear β-catenin was down-regulated upon EP treatment, subsequently reducing the Cyclin D1 and c-Myc expression levels. Meanwhile, the protein level of protein tyrosine phosphatase SHP2 was up-regulated in EP treated cells, whereas Src kinase activity was inhibited. Both activation of SHP2 phosphatase and inhibition of Src kinase decreased the phosphorylation level of transducer and activator of STAT3 protein, which was implicated in oncogenesis. On the other hand, EP remarkably inhibited the expression and secretion of VEGF-C, implying its involvement in counteracting tumor angiogenesis. Moreover, EP treatment showed comparable cytotoxic effect with β-catenin knock-down or STAT3 inhibition. Taken together, our results demonstrated that EP showed antitumor effects toward ovarian cancer cells through both β-catenin and STAT3 signaling pathways, making it a promising candidate for drug development.

  10. Prophylactic Oophorectomy: Reducing the U.S. Death Rate from Epithelial Ovarian Cancer. A Continuing Debate.

    Science.gov (United States)

    Piver

    1996-01-01

    If instead of the title "Prophylactic Oophorectomy: Reducing the U.S. Death Rate from Epithelial Ovarian Cancer," the title were "Drug X Reducing the U.S. Death Rate from Epithelial Ovarian Cancer," there would be great media and medical attention worldwide to such a report. Correctly so. Regrettably, there probably is no new Drug X in the foreseeable future that will significantly reduce the death rate from ovarian cancer, be it Taxol®, taxotere, topotecan, gemcitabine, or liposomal doxorubicin-although each may result in significant responses and some prolongation of median survival. Epithelial ovarian cancer is a much more complex disease than anyone envisioned, when it was believed that extensive debulking surgery and the newest cytotoxic chemotherapy would radically reduce the death rate from ovarian cancer in the United States. Over 20 years after the first patient was treated with cisplatin for epithelial ovarian cancer, the annual death rate from ovarian cancer continued to increase. Just in the past decade, the number of women in the United States dying from ovarian cancer has increased 18% (Fig. 1) [1]. Although ovarian cancer is estimated to account for 26,700 cases and 14,800 deaths in 1996, it is a low-prevalence disease in comparison with breast cancer, which in 1996 is estimated to account for 185,700 cases and 44,560 deaths. Inexplicably, similar to breast cancer, the lifetime risk for ovarian cancer in the United States continues to increase. The most recent Surveillance, Epidemiology and End Results (SEER) calculations of lifetime risk for ovarian cancer are that 1 in 55 women will develop ovarian cancer over their lifetime, or 1.8%, up from the 1970 figures of 1 in 70, or 1.4% [2]. The 1.8% baseline lifetime risk for the general population is used to estimate the lifetime risk of known ovarian cancer risk factors (Table 1). Even utilizing what are now believed to be two of the most effective cytotoxic drugs against stage III and IV epithelial

  11. 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

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    included in this analysis. Unconditional logistic regression was used to model the association between each SNP and ovarian cancer risk and two-sided P-values are reported. Overall, risk of ovarian cancer was not associated with any of the three variants studied. However, in histopathological subtype...

  13. Ovarian Cancers: Genetic Abnormalities, Tumor Heterogeneity and Progression, Clonal Evolution and Cancer Stem Cells

    Science.gov (United States)

    Castelli, Germana; Pelosi, Elvira

    2018-01-01

    Four main histological subtypes of ovarian cancer exist: serous (the most frequent), endometrioid, mucinous and clear cell; in each subtype, low and high grade. The large majority of ovarian cancers are diagnosed as high-grade serous ovarian cancers (HGS-OvCas). TP53 is the most frequently mutated gene in HGS-OvCas; about 50% of these tumors displayed defective homologous recombination due to germline and somatic BRCA mutations, epigenetic inactivation of BRCA and abnormalities of DNA repair genes; somatic copy number alterations are frequent in these tumors and some of them are associated with prognosis; defective NOTCH, RAS/MEK, PI3K and FOXM1 pathway signaling is frequent. Other histological subtypes were characterized by a different mutational spectrum: LGS-OvCas have increased frequency of BRAF and RAS mutations; mucinous cancers have mutation in ARID1A, PIK3CA, PTEN, CTNNB1 and RAS. Intensive research was focused to characterize ovarian cancer stem cells, based on positivity for some markers, including CD133, CD44, CD117, CD24, EpCAM, LY6A, ALDH1. Ovarian cancer cells have an intrinsic plasticity, thus explaining that in a single tumor more than one cell subpopulation, may exhibit tumor-initiating capacity. The improvements in our understanding of the molecular and cellular basis of ovarian cancers should lead to more efficacious treatments. PMID:29389895

  14. 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

    Because both ovarian and breast cancer are hormone-related and are known to have some predisposition genes in common, we evaluated 11 of the most significant hits (six with confirmed associations with breast cancer) from the breast cancer genome-wide association study for association with invasive...... cases and 6308 controls from eight independent studies. Only rs4954956 was significantly associated with ovarian cancer risk both in the replication study and in combined analyses. This association was stronger for the serous histological subtype [per minor allele odds ratio (OR) 1.07 95% CI 1.......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...

  15. Risk of breast cancer after a diagnosis of ovarian cancer in BRCA mutation carriers: Is preventive mastectomy warranted?

    Science.gov (United States)

    McGee, Jacob; Giannakeas, Vasily; Karlan, Beth; Lubinski, Jan; Gronwald, Jacek; Rosen, Barry; McLaughlin, John; Risch, Harvey; Sun, Ping; Foulkes, William D; Neuhausen, Susan L; Kotsopoulos, Joanne; Narod, Steven A

    2017-05-01

    Preventive breast surgery and MRI screening are offered to unaffected BRCA mutation carriers. The clinical benefit of these two modalities has not been evaluated among mutation carriers with a history of ovarian cancer. Thus, we sought to determine whether or not BRCA mutation carriers with ovarian cancer would benefit from preventive mastectomy or from MRI screening. First, the annual mortality rate for ovarian cancer patients was estimated for a cohort of 178 BRCA mutation carriers from Ontario, Canada. Next, the actuarial risk of developing breast cancer was estimated using an international registry of 509 BRCA mutation carriers with ovarian cancer. A series of simulations was conducted to evaluate the reduction in the probability of death (from all causes) associated with mastectomy and with MRI-based breast surveillance. Cox proportional hazards models were used to evaluate the impacts of mastectomy and MRI screening on breast cancer incidence as well as on all-cause mortality. Twenty (3.9%) of the 509 patients developed breast cancer within ten years following ovarian cancer diagnosis. The actuarial risk of developing breast cancer at ten years post-diagnosis, conditional on survival from ovarian cancer and other causes of mortality was 7.8%. Based on our simulation results, among all BRCA mutation-carrying patients diagnosed with stage III/IV ovarian cancer at age 50, the chance of dying before age 80 was reduced by less than 1% with MRI and by less than 2% with mastectomy. Greater improvements in survival with MRI or mastectomy were observed for women who had already survived 10years after ovarian cancer, and for women with stage I or II ovarian cancer. Among BRCA mutation-carrying ovarian cancer patients without a personal history of breast cancer, neither preventive mastectomy nor MRI screening is warranted, except for those who have survived ovarian cancer without recurrence for ten years and for those with early stage ovarian cancer. Copyright © 2017

  16. 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.

  17. Pelvic-peritoneal tuberculosis mimicking ovarian cancer

    International Nuclear Information System (INIS)

    Imtiaz, S.; Siddiqui, N.

    2012-01-01

    Pelvic-peritoneal tuberculosis is a common extrapulmonary site in young females mimicking an advanced ovarian malignancy. We present 2 cases with the classical triad of advanced-stage ovarian carcinoma-ascites, abdominopelvic masses and elevated serum CA-125 levels. Laparoscopic examination revealed peritoneal nodules which on biopsy showed granulomatous inflammation and no malignant cells. Patients were started on anti-tuberculous therapy and on follow-up their symptoms as well as CA-125 levels normalized. Medical awareness of peritoneal tuberculosis is lacking and many young women with this disease undergo unnecessary extended surgery. Diagnostic laparoscopy combined with peritoneal biopsy seems to be a sufficient and safe method to provide a definitive diagnosis for this curable infection. If left untreated, the disease may disseminate and result in significant organ dysfunctions particularly infertility. (author)

  18. 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.

  19. 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...

  20. 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...

  1. 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

    . A marginally significant association was found for RB1 when all studies were included [ordinal odds ratio (OR) 0.88 (95% confidence interval (CI) 0.79-1.00) p = 0.041 and dominant OR 0.87 (95% CI 0.76-0.98) p = 0.025]; when the studies that originally suggested an association were excluded, the result......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...... (rs144848) in BRCA2, rs2854344 in intron 17 of RB1, rs2811712 5' flanking CDKN2A, rs523349 in the 3' UTR of SRD5A2, D302H (rs1045485) in CASP8 and L10P (rs1982073) in TGFB1. Fourteen studies genotyped 4,624 invasive epithelial ovarian cancer cases and 8,113 controls of white non-Hispanic origin...

  2. Cancer prevalence in 129 breast-ovarian cancer families tested for ...

    African Journals Online (AJOL)

    As expected, female breast and ovarian cancer was significantly increased in all three groups. Furthermore, male breast cancer was significantly elevated in the BRCA2-positive and BRCA-negative groups. Stomach cancer prevalence was significantly elevated in the BRCA2-positive families compared with the general ...

  3. BRCAness profile of sporadic ovarian cancer predicts disease recurrence.

    Directory of Open Access Journals (Sweden)

    Weiya Z Wysham

    Full Text Available The consequences of defective homologous recombination (HR are not understood in sporadic ovarian cancer, nor have the potential role of HR proteins other than BRCA1 and BRCA2 been clearly defined. However, it is clear that defects in HR and other DNA repair pathways are important to the effectiveness of current therapies. We hypothesize that a subset of sporadic ovarian carcinomas may harbor anomalies in HR pathways, and that a BRCAness profile (defects in HR or other DNA repair pathways could influence response rate and survival after treatment with platinum drugs. Clinical availability of a BRCAness profile in patients and/or tumors should improve treatment outcomes.To define the BRCAness profile of sporadic ovarian carcinoma and determine whether BRCA1, PARP, FANCD2, PTEN, H2AX, ATM, and P53 protein expression correlates with response to treatment, disease recurrence, and recurrence-free survival.Protein microarray analysis of ovarian cancer tissue was used to determine protein expression levels for defined DNA repair proteins. Correlation with clinical and pathologic parameters in 186 patients with advanced stage III-IV and grade 3 ovarian cancer was analyzed using Chi square, Kaplan-Meier method, Cox proportional hazard model, and cumulative incidence function.High PARP, FANCD2 and BRCA1 expressions were significantly correlated with each other; however, elevated p53 expression was associated only with high PARP and FANCD2. Of all patients, 9% recurred within the first year. Among early recurring patients, 41% had high levels of PARP, FANCD2 and P53, compared to 19.5% of patients without early recurrence (p = 0.04. Women with high levels of PARP, FANCD2 and/or P53 had first year cumulative cancer incidence of 17% compared with 7% for the other groups (P = 0.03.Patients with concomitantly high levels of PARP, FANCD2 and P53 protein expression are at increased risk of early ovarian cancer recurrence and platinum resistance.

  4. 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.

  5. TUBAL LIGATION, REPRODUCTIVE EXPERIENCES AND RISK OF OVARIAN CANCER- A PROSPECTIVE 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. Tubal ligation confers long-term protection against ovarian cancer. This observational study examines the factors affecting the ovarian cancer risk and also studies the correlation between ovarian cancer risks with reproductive experiences. 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. A binary logit regression analysis was conducted to study the factors that are affecting the ovarian cancer. The Chi-square test was done to find the association of ovarian cancer risk with different reproductive experiences. RESULTS We found that months of lactation, tubal ligation and oral contraceptive pills had a negative impact on ovarian cancer risk. Our study also proved that age of first pregnancy, age of menarche and age of menopause had a significant association with ovarian cancer risk. CONCLUSION Our findings signify the importance of providing awareness to the public regarding the prevalence, symptomatology, screening/diagnostic techniques, treatment modalities and prognosis 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. We recommend the promotion of tubal ligation as a permanent method of contraception in those who have completed their families.

  6. The diagnostic value of serum HE4 and CA-125 and ROMA index in ovarian cancer.

    Science.gov (United States)

    Wei, S U; Li, Hui; Zhang, Bei

    2016-07-01

    Ovarian cancer is a common malignancy of the female reproductive system. Tumor markers serve as tools in the diagnosis of the disease. The aim of the present study was to determine the diagnostic value of sera levels of carbohydrate antigen-125 (CA-125), human epididymis protein 4 (HE4) as well as the area under the curve of the receiver operating characteristic (ROC) and the risk of ovarian malignancy algorithm (ROMA) index in ovarian cancer. The sera were measured using an electrochemiluminescence immunoassay on 158 individuals (64 patients with ovarian cancer, 64 with ovarian benign tumor and 30 healthy individuals) between September 2013 and May 2015. The results showed that levels of HE4 and CA-125 in the sera of the ovarian benign tumor group as well as their ROMA index were significantly higher (PCA-125 was significantly higher (PCA-125. In the ovarian cancer group, the areas under ROC curves of ROMA, HE4 and CA-125 were 0.994, 0.990 and 0.941, respectively. The specificity and positive predictive value of HE4 in the premenopausal ovarian cancer group reached 98.36 and 95%, respectively. In conclusion, the results showed that the serum level of HE4 and the ROMA index are important indicators in the diagnosis of ovarian cancer. However, in addition to HE4 and CA-125 detection, the ROMA index is extremely valuable in improving the diagnostic efficiency of ovarian cancer.

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

    Science.gov (United States)

    Doherty, Jennifer A.; Rossing, Mary Anne; Cushing-Haugen, Kara L.; Chen, Chu; Van Den Berg, David J.; Wu, Anna H.; Pike, Malcolm C.; Ness, Roberta B.; Moysich, Kirsten; Chenevix-Trench, Georgia; Beesley, Jonathan; Webb, Penelope M.; Chang-Claude, Jenny; Wang-Gohrke, Shan; Goodman, Marc T.; Lurie, Galina; Thompson, Pamela J.; Carney, Michael E.; Hogdall, Estrid; Kjaer, Susanne Kruger; Hogdall, Claus; Goode, Ellen L.; Cunningham, Julie M.; Fridley, Brooke L.; Vierkant, Robert A.; Berchuck, Andrew; Moorman, Patricia G.; Schildkraut, Joellen M.; Palmieri, Rachel T.; Cramer, Daniel W.; Terry, Kathryn L.; Yang, Hannah P.; Garcia-Closas, Montserrat; Chanock, Stephen; Lissowska, Jolanta; Song, Honglin; Pharoah, Paul D.P.; Shah, Mitul; Perkins, Barbara; McGuire, Valerie; Whittemore, Alice S.; Di Cioccio, Richard A.; Gentry-Maharaj, Aleksandra; Menon, Usha; Gayther, Simon A.; Ramus, Susan J.; Ziogas, Argyrios; Brewster, Wendy; Anton-Culver, Hoda; Pearce, Celeste Leigh

    2010-01-01

    We genotyped 13 single nucleotide polymorphisms (SNPs) in the estrogen receptor alpha gene (ESR1) region in three population-based case-control studies of epithelial ovarian cancer conducted in the United States, comprising a total of 1,128 and 1,866 non-Hispanic white invasive cases and controls, respectively. A SNP 19 kb downstream of ESR1 (rs2295190, G-to-T change) was associated with invasive ovarian cancer risk, with a per-T-allele odds ratio (OR) of 1.24 (95% confidence interval (CI), 1.06–1.44, p=0.006). rs2295190 is a non-synonymous coding SNP in a neighboring gene called spectrin repeat containing, nuclear envelope 1 (SYNE1) which is involved in nuclear organization and structural integrity, function of the Golgi apparatus, and cytokinesis. An isoform encoded by SYNE1 has been reported to be downregulated in ovarian and other cancers. rs2295190 was genotyped in an additional 12 studies through the Ovarian Cancer Association Consortium, with 5,279 invasive epithelial cases and 7,450 controls. The per-T-allele OR for this 12-study set was 1.09 (95% CI, 1.02–1.17, p=0.017). Results for the serous subtype in the 15 combined studies were similar to those overall (n=3,545; OR=1.09, 95% CI, 1.01–1.18, p=0.025), and our findings were strongest for the mucinous subtype (n=447; OR=1.32, 95% CI, 1.11–1.58, p=0.002). No association was observed for the endometrioid subtype. In an additional analysis of 1,459 borderline ovarian cancer cases and 7,370 controls, rs2295190 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. PMID:20056644

  8. 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

  9. 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...

  10. 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

  11. 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.

  12. [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.

  13. Sex Steroid Hormone Receptor Expression Affects Ovarian Cancer Survival

    DEFF Research Database (Denmark)

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

    2015-01-01

    BACKGROUND AND AIMS: Although most ovarian cancers express estrogen (ER), progesterone (PR), and androgen (AR) receptors, they are currently not applied in clinical decision making. We explored the prognostic impact of sex steroid hormone receptor protein and mRNA expression on survival in epithe......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...... not provide prognostic information. Patients whose tumors coexpressed PR and AR had the most favorable prognosis, and this effect was retained in multivariable analyses. Analyses of the corresponding genes using an independent data set revealed differences among the molecular subtypes, but no clear...

  14. Exploring alternative ovarian cancer biomarkers using innovative nanotechnology strategies.

    Science.gov (United States)

    Castro, Cesar M; Im, Hyungsoon; Le, Christine; Lee, Hakho; Weissleder, Ralph; Birrer, Michael J

    2015-03-01

    Our increased understanding of ovarian cancer's blueprints (mediated by DNA and RNA) and behavior (mediated by proteins) points to wide differences across patients that cannot be depicted by histology alone. Conventional diagnosis usually entails an adequate tissue biopsy, which limits serial testing. There is thus a motivation to shift towards easier to obtain clinical samples (e.g., ascites or blood). In response, investigators are increasingly leveraging alternative circulating biomarkers in blood or proximal fluids and harnessing novel profiling platforms to help explore treatment-related effects on such biomarkers in serial fashion. In this review, we discuss how new nanotechnologies we developed intersect with alternative ovarian cancer biomarkers for improved understanding of metastases and therapeutic response.

  15. Deciphering the molecular nature of ovarian cancer biomarker CA125.

    Science.gov (United States)

    Weiland, Florian; Martin, Karina; Oehler, Martin K; Hoffmann, Peter

    2012-01-01

    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.

  16. 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.

  17. Chronic recreational physical inactivity and epithelial ovarian cancer risk

    DEFF Research Database (Denmark)

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

    2016-01-01

    , 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......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....... 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...

  18. 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...

  19. A prospective study of phobic anxiety, risk of ovarian cancer, and survival among patients.

    Science.gov (United States)

    Poole, Elizabeth M; Kubzansky, Laura D; Sood, Anil K; Okereke, Olivia I; Tworoger, Shelley S

    2016-05-01

    In ovarian cancer patients and mouse models, psychosocial stress is associated with higher circulating markers of angiogenesis and cell migration, impaired immune response, and increasing tumor burden and aggressiveness. In the Nurses' Health Studies (NHS/NHSII), we assessed whether phobic anxiety, a marker of chronic distress, was associated with risk of incident ovarian cancer as well as survival among ovarian cancer patients. We used Cox proportional hazards regression to model the relative risks (RRs) and 95 % confidence intervals (CI) of ovarian cancer incidence and survival by categories of the Crown-Crisp phobic anxiety index (CCI). We identified 779 cases of ovarian cancer during 2,497,892 person-years of follow-up. For baseline CCI (NHS: 1988; NHSII: 1993), we observed a statistically nonsignificant increased risk of epithelial ovarian cancer (RR for CCI ≥ 4 vs. 0 or 1: 1.14; 95 % CI 0.96-1.36). However, when we updated CCI (NHS: 2004; NHSII: 2005), the associations were attenuated. Pre-diagnosis CCI was not associated with ovarian cancer survival (RR for ≥4 vs. 0 or 1: 1.00; 95 % CI 0.77-1.31); results were similar for post-diagnosis CCI. Distress, as measured by phobic anxiety symptoms, was not associated with ovarian cancer risk, although we cannot rule out a modest association. Future research should explore the role of phobic anxiety and other forms of psychological distress and ovarian cancer risk and survival.

  20. IL-15 super-agonist (ALT-803) enhances natural killer (NK) cell function against ovarian cancer.

    Science.gov (United States)

    Felices, M; Chu, S; Kodal, B; Bendzick, L; Ryan, C; Lenvik, A J; Boylan, K L M; Wong, H C; Skubitz, A P N; Miller, J S; Geller, M A

    2017-06-01

    Natural killer (NK) cells represent a powerful immunotherapeutic target as they lyse tumors directly, do not require differentiation, and can elicit potent inflammatory responses. The objective of these studies was to use an IL-15 super-agonist complex, ALT-803 (Altor BioScience Corporation), to enhance the function of both normal and ovarian cancer patient derived NK cells by increasing cytotoxicity and cytokine production. NK cell function from normal donor peripheral blood mononuclear cells (PBMCs) and ovarian cancer patient ascites was assessed using flow cytometry and chromium release assays ±ALT-803 stimulation. To evaluate the ability of ALT-803 to enhance NK cell function in vivo against ovarian cancer, we used a MA148-luc ovarian cancer NOD scid gamma (NSG) xenogeneic mouse model with transferred human NK cells. ALT-803 potently enhanced functionality of NK cells against all ovarian cancer cell lines with significant increases seen in CD107a, IFNγ and TNFα expression depending on target cell line. Function was also rescued in NK cells derived from ovarian cancer patient ascites. Finally, only animals treated with intraperitoneal ALT-803 displayed an NK dependent significant decrease in tumor. ALT-803 enhances NK cell cytotoxicity against ovarian cancer in vitro and in vivo and is able to rescue functionality of NK cells derived from ovarian cancer patient ascites. These findings suggest that ALT-803 has the potential to enhance NK cell-based immunotherapeutic approaches for the treatment of ovarian cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

  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. Targeting the Mevalonate Pathway to Reduce Mortality from Ovarian Cancer

    Science.gov (United States)

    2015-10-01

    Necropsy was performed at the endpoint, and histopathologic examination of internal organs including liver, spleen, kidney, heart, intestine , and brain did...activation (31). Rho GTPases are closely involved in Figure 3. Lovastatin induces autophagy and cell-cycle arrest in ovarian cancer cells. A, SKOV3 and...indirectly silence the expression of MCM genes, leading to cell- cycle arrest and accumulation of DNA damage. Although the doses of lovastatin used in our

  3. Identifying Determinants of PARP Inhibitor Sensitivity in Ovarian Cancer

    Science.gov (United States)

    2016-10-01

    cisplatin sensitivity (Fig. 3A). MDA-MB-436 cells harbor a BRCA15396+1G>A mutation resulting in protein misfolding , undetectable BRCA1 and RAD51...the DNA damage response; and 3) To identify small molecules that kill N-terminal deficient BRCA1 protein expressing cells. Procuring Contracting...hypothesized that a range of common ovarian cancer predisposing germ-line BRCA1 gene mutations produce semi-functional proteins that are capable of

  4. Subcloning of ovarian cancer cell lines.

    Science.gov (United States)

    Grunt, T W

    2001-01-01

    Cellular heterogeneity of malignant tissues is a well-known phenomenon (1). Intralineal/intraclonal diversity may be explained in part by proposing the concept of a hierarchically ordered, differentiating and self-renewing stem cell system for transformed cell populations (2). However, in many solid tumors, the stem cells are not easily accessible to phenotypic identification. In the past, density gradient centrifugation was successfully used to separate cells from tumors and from cell lines into distinct subpopulations (3-5). Using Percoll density gradients, we isolated undifferentiated clonogenic tumor stem-cell fractions from HOC-7 human ovarian adenocarcinoma cells. In addition, we also identified a low-density cell subpopulation formed by large, vacuolated, slowly growing, adenoid differentiated cells with very low clonogenic activity (6-11). Further characterization of these cell fractions in terms of stability of the isolated phenotypes is essential for the assessment of their biological significance. Subcloning of the isolated cell fractions by limiting dilution culture (12) followed by long-term culture yielded three permanent monoclonal sublines, which reveal a stable adenoid differentiated phenotype, and three subclones representing undifferentiated, clonogenic tumor stem cells (13). These data demonstrate that the isolated phenotypes represent distinct cell entities reflecting specific stages of ovarian surface epithelial cell differentiation.

  5. 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.

  6. Dietary phytoestrogens and the risk of ovarian cancer in the women's lifestyle and health cohort study.

    Science.gov (United States)

    Hedelin, Maria; Löf, Marie; Andersson, Therese M-L; Adlercreutz, Herman; Weiderpass, Elisabete

    2011-02-01

    Dietary intake of phytoestrogens has been inversely associated to hormone-dependent cancers, such as prostate and breast cancers. Few studies have investigated the association between ovarian cancer and intake of phytoestrogens. We evaluated the associations between intake of phytoestrogens (isoflavonoids/lignans/coumestrol) and fiber (vegetable/cereal) and risk of ovarian cancer. In 1991-1992 a prospective population-based cohort study among Swedish women was conducted, including 47,140 women with complete dietary questionnaire data. During follow-up until December 2007, 163 women developed invasive (n = 117) and borderline (n = 46) ovarian cancers. The median follow-up time was 16 years and total person year was 747,178. Cox proportional hazards models were conducted to estimate multivariate risk ratios, 95% CI for associations with risk of ovarian cancer. We found no association between intake of phytoestrogens or fiber and overall ovarian cancer risk. In addition, we found no statistically significant association between intake of specific food items rich in phytoestrogens (berries, nuts, beans/soy, and crisp or whole-grain bread) and ovarian cancer risk overall. Fiber and coumestrol was inversely associated with borderline ovarian cancer, but not with invasive ovarian cancer. We found no association between intake of phytoestrogens or fiber and overall ovarian cancer risk. Phytoestrogens do not play a major etiologic role in ovarian cancer, at least among women in this Swedish cohort with low bean/soy intake. However, our results of a difference in the effect of fiber or coumestrol between invasive and borderline ovarian cancer need to be evaluated in larger studies. ©2011 AACR.

  7. Non-epithelial Ovarian Cancer: Elucidating Uncommon Gynaecological Malignancies.

    Science.gov (United States)

    Boussios, Stergios; Zarkavelis, George; Seraj, Esmeralda; Zerdes, Ioannis; Tatsi, Konstantina; Pentheroudakis, George

    2016-10-01

    Non-epithelial ovarian cancers (NEOC) are a group of fascinating but uncommon malignancies which can be extremely challenging to treat. Collectively, these tumours only represent 10-15% of all ovarian cancers and occur in all age groups from childhood to old age. This broad term includes diverse tumours of germ cell origin, sex cord-stromal cell origin, as well as extremely rare types of ovarian cancer, such as small-cell carcinomas and sarcomas, each of which require specialist management. It is imperative that these rare tumours are managed with accurate diagnosis, staging and treatment in order to optimize patient outcomes. The aetiology and molecular origins of each sub-group of NEOC remain poorly understood and international cooperation to facilitate high quality translational research is needed. This review summarizes the published literature on the incidence, clinical presentation, pathology, therapeutic interventions, survival and prognostic factors of each sub-type of NEOC. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  8. The Prognostic 97 Chemoresponse Gene Signature in Ovarian Cancer.

    Science.gov (United States)

    Matondo, Abel; Jo, Yong Hwa; Shahid, Muhammad; Choi, Tae Gyu; Nguyen, Minh Nam; Nguyen, Ngoc Ngo Yen; Akter, Salima; Kang, Insug; Ha, Joohun; Maeng, Chi Hoon; Kim, Si-Young; Lee, Ju-Seog; Kim, Jayoung; Kim, Sung Soo

    2017-08-29

    Patient diagnosis and care would be significantly improved by understanding the mechanisms underlying platinum and taxane resistance in ovarian cancer. Here, we aim to establish a gene signature that can identify molecular pathways/transcription factors involved in ovarian cancer progression, poor clinical outcome, and chemotherapy resistance. To validate the robustness of the gene signature, a meta-analysis approach was applied to 1,020 patients from 7 datasets. A 97-gene signature was identified as an independent predictor of patient survival in association with other clinicopathological factors in univariate [hazard ratio (HR): 3.0, 95% Confidence Interval (CI) 1.66-5.44, p = 2.7E-4] and multivariate [HR: 2.88, 95% CI 1.57-5.2, p = 0.001] analyses. Subset analyses demonstrated that the signature could predict patients who would attain complete or partial remission or no-response to first-line chemotherapy. Pathway analyses revealed that the signature was regulated by HIF1α and TP53 and included nine HIF1α-regulated genes, which were highly expressed in non-responders and partial remission patients than in complete remission patients. We present the 97-gene signature as an accurate prognostic predictor of overall survival and chemoresponse. Our signature also provides information on potential candidate target genes for future treatment efforts in ovarian cancer.

  9. Association study of prostate cancer susceptibility variants with risks of invasive ovarian, breast, and colorectal cancer

    DEFF Research Database (Denmark)

    Song, H.; Koessler, T.; Ahmed, S.

    2008-01-01

    cancer [per minor allele OR, 1.19; 95% confidence interval (95% CI), 1.04-1.37; P(trend) = 0.012]. This association was stronger for the serous histologic subtype (OR, 1.29; 95% CI, 1.09-1.53; P = 0.003). SNP rs7931342 (chromosome 11q13) showed some evidence of association with breast cancer (per minor...... ovarian, colorectal, and breast cancer. Twelve prostate cancer-associated tag SNPs were genotyped in ovarian (2,087 cases/3,491 controls), colorectal (2,148 cases/2,265 controls) and breast (first set, 4,339 cases/4,552 controls; second set, 3,800 cases/3,995 controls) case-control studies. The primary...... may also be associated with ovarian and breast cancer susceptibility. However, the effects are modest and warrant replication in larger studies Udgivelsesdato: 2008/11/1...

  10. 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.

  11. Chlamydia Peritonitis and Ascites Mimicking Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    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.

  12. Cost of Care for the Initial Management of Ovarian Cancer.

    Science.gov (United States)

    Bercow, Alexandra S; Chen, Ling; Chatterjee, Sudeshna; Tergas, Ana I; Hou, June Y; Burke, William M; Ananth, Cande V; Neugut, Alfred I; Hershman, Dawn L; Wright, Jason D

    2017-12-01

    To examine the cost of care during the first year after a diagnosis of ovarian cancer, estimate the sources of cost, and explore the out-of-pocket costs. We performed a retrospective cohort study of women with ovarian cancer diagnosed from 2009 to 2012 who underwent both surgery and adjuvant chemotherapy using the Truven Health MarketScan database. This database is comprised of patients covered by commercial insurance sponsored by more than 100 employers in the United States. Medical expenditures, including physician reimbursement, for a 12-month period beginning on the date of surgery were estimated. All payments were examined, including out-of-pocket costs for patients. Payments were divided into expenditures for inpatient care, outpatient care (including chemotherapy), and outpatient drug costs. The 12-month treatment period was divided into three phases: surgery to 30 days (operative period), 1-6 months (adjuvant therapy), and 6-12 months after surgery. The primary outcome was the overall cost of care within the first year of diagnosis of ovarian cancer; secondary outcomes included assessment of factors associated with cost. A total of 26,548 women with ovarian cancer who underwent surgery were identified. After exclusion of patients with incomplete insurance enrollment or coverage, those who did not undergo chemotherapy, and those with capitated plans, our cohort consisted of 5,031 women. The median total medical expenditures per patient during the first year after the index procedure were $93,632 (interquartile range $62,319-140,140). Inpatient services accounted for $30,708 (interquartile range $20,102-51,107; 37.8%) in expenditures, outpatient services $52,700 (interquartile range $31,210-83,206; 58.3%), and outpatient drug costs $1,814 (interquartile range $603-4,402; 3.8%). The median out-of-pocket expense was $2,988 (interquartile range $1,649-5,088). This included $1,509 (interquartile range $705-2,878) for outpatient services, $589 (interquartile range

  13. Predictors of pretreatment CA125 at ovarian cancer diagnosis

    DEFF Research Database (Denmark)

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

    2017-01-01

    in CA125 between studies and linear regression to estimate the association between epidemiologic factors and tumor characteristics and pretreatment CA125 levels. RESULTS: In age-adjusted models, older age, history of pregnancy, history of tubal ligation, family history of breast cancer, and family...... history of ovarian cancer were associated with higher CA125 levels while endometriosis was associated with lower CA125 levels. After adjusting for tumor-related characteristics (stage, histology, grade), body mass index (BMI) higher than 30 kg/m2was associated with 10% (95% CI 2, 19%) higher CA125 levels...

  14. Proteome profiling analysis of human ovarian cancer serum samples

    International Nuclear Information System (INIS)

    Cognetti, F.; Citro, G.

    2009-01-01

    Mass Spectrometry represents a powerful tool in cancer research to discovery of potential bio markers through peak identification from serum profiling. By using high resolution MALDITOF and bioinformatic analysis almost 400 serum sample homogeneously distributed between biopsy confirmed ovarian cancer and high risk serum samples were analyzed. Each serum sample run in duplicate and whole serum sample preparation procedure has been performed by Hamilton Star Robot in order to reduce bias and the replicates with a low Pearson coefficient are removed. After automated reverse phase magnetic beads separation the samples were tested in MALDI-TOF

  15. Predisposing genes in hereditary breast and ovarian cancer

    OpenAIRE

    Huusko, P. (Pia)

    1999-01-01

    Abstract In the present study, mutations in BRCA1 and BRCA2, the two major genes predisposing individuals to hereditary breast and ovarian cancer, were screened in Finnish and Turkish cancer families. Germline BRCA1 mutations were found in 7% (6/88) and BRCA2 mutations in 6% (5/88) of the Finnish families studied in Oulu. Two distinct BRCA1 (3745delT, 4216nt-2A→G) and three BRCA2 (999delTCAAA, 6503delTT, 9346nt-2A→G) mutations were identified, all of which are recurrently found in Finland....

  16. 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.

  17. 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

    , respectively. A SNP 19 kb downstream of ESR1 (rs2295190, G-to-T change) was associated with invasive ovarian cancer risk, with a per-T-allele odds ratio (OR) of 1.24 [95% confidence interval (CI), 1.06-1.44, P = 0.006]. rs2295190 is a nonsynonymous coding SNP in a neighboring gene called spectrin repeat......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...... 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...

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

    DEFF Research Database (Denmark)

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

    2010-01-01

    , respectively. A SNP 19 kb downstream of ESR1 (rs2295190, G-to-T change) was associated with invasive ovarian cancer risk, with a per-T-allele odds ratio (OR) of 1.24 [95% confidence interval (CI), 1.06-1.44, P = 0.006]. rs2295190 is a nonsynonymous coding SNP in a neighboring gene called spectrin repeat...... through the Ovarian Cancer Association Consortium, with 5,279 invasive epithelial cases and 7,450 controls. The per-T-allele OR for this 12-study set was 1.09 (95% CI, 1.02-1.17; P = 0.017). Results for the serous subtype in the 15 combined studies were similar to those overall (n = 3,545; OR, 1.09; 95......% CI, 1.01-1.18; P = 0.025), and our findings were strongest for the mucinous subtype (n = 447; OR, 1.32; 95% CI, 1.11-1.58; P = 0.002). No association was observed for the endometrioid subtype. In an additional analysis of 1,459 borderline ovarian cancer cases and 7,370 controls, rs2295190...

  19. 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

  20. 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

  1. Outcome of fertility preserving surgery in early stage ovarian cancer

    International Nuclear Information System (INIS)

    Fakhr, I.; Ramzy, S.; Mohamed, A.; Abd-Allah, M.; Saber, A.

    2013-01-01

    Aim: To assess the role of fertility preserving surgery in treatment of patients with stage I A, G1 or G2 ovarian carcinoma without adjuvant chemotherapy. Patients and methods: From 2006 to 2008, a prospective non-randomized study recruited 150 women, with suspicious early malignant ovarian mass. Results: Among the 150 explored patients, only 43 (28.6%) patients underwent exploration. Only 32/150 (21.3%) patients had proven stage IA, either G1 or G2, epithelial ovarian cancer. Among the 32 patients, 22 (68.7%) patients were nullipara while 10 (32.1%) had one child. All patients had unilateral tumors; 26 (81.25%) patients had G1 and 6 (18.75%) patients had G2 tumors; 24/32 (75.0%) tumors were serous, 6/32 (18.7%) were mucinous and 2/32 (6.2%) were endometrioid, and none was clear cell type. The median follow up period was 58.5 months (ranged: 48- 72 months). Two patients (6.7%) were lost during follow up; data will be presented for the remaining 30 patients. One patient, at 27th month of follow up, had open abdominal exploration to investigate abnormal pelvic mass on routine ultrasound follow up examination. Frozen section revealed recurrent invasive mucinous tumor. She underwent radical surgery with pelvic and para-aortic lymph node dissection, followed by adjuvant chemotherapy, and remained free of disease, for the remaining 29 months of the follow up period. Neither distant metastases nor mortality were reported among our patients.Conclusion: Fertility preserving surgery can be considered a safe treatment strategy in patients with stage IA, G1 of (32 ovarian carcinoma Conclusion: Fertility preserving surgery can be considered a safe treatment strategy in patients with stage IA, G1 of G2 ovarian carcinoma

  2. 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)

    2018-01-09

    Mixed Mesodermal (Mullerian) Tumor; Ovarian Carcinosarcoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage I Ovarian Cancer; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Cancer; Stage IA Uterine Sarcoma AJCC v7; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Cancer; Stage IB Uterine Sarcoma AJCC v7; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Cancer; Stage IC Uterine Sarcoma AJCC v7; Stage II Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIA Uterine Sarcoma AJCC v7; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIB Uterine Sarcoma AJCC v7; 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 AJCC v7; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIB Uterine Sarcoma AJCC v7; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IIIC Uterine Sarcoma AJCC v7; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer; Stage IVA Uterine Sarcoma AJCC v7; Stage IVB Uterine Sarcoma AJCC v7; Uterine Carcinosarcoma

  3. 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...

  4. Thiol-reducing agents prevent sulforaphane-induced growth inhibition in ovarian cancer cells

    OpenAIRE

    Kim, Seung Cheol; Choi, Boyun; Kwon, Youngjoo

    2017-01-01

    ABSTRACT The inhibitory potential of sulforaphane against cancer has been suggested for different types of cancer, including ovarian cancer. We examined whether this effect is mediated by mitogen-activated protein kinase (MAPK) and reactive oxygen species (ROS), important signaling molecules related to cell survival and proliferation, in ovarian cancer cells. Sulforaphane at a concentration of 10 μM effectively inhibited the growth of cancer cells. Use of specific inhibitors revealed that act...

  5. General Information about Ovarian Epithelial Cancer

    Science.gov (United States)

    ... the ovaries, through the fallopian tubes, to the uterus. Cancer sometimes begins at the end of the fallopian ... into stage IIA and stage IIB. Stage IIA : Cancer has spread from where it first formed to the uterus and/or the fallopian tubes and/or the ...

  6. Olaparib recommendations for ovarian cancer patients.

    Science.gov (United States)

    Johnson, Peter; Westcott, Gemma

    2016-01-01

    Peter Johnson speaks to Gemma Westcott, Commissioning Editor: Peter Johnson is Professor of Medical Oncology at the University of Southampton and Chief Clinician for Cancer Research UK. He graduated from Cambridge University and St Thomas's Medical School (UK). He trained in oncology at St Bartholomew's Hospital, London, where he was an Imperial Cancer Research Fund (ICRF) Clinical Research Fellow and completed his doctoral research on the Bcl-2 gene, its potential as a therapeutic target in lymphoma and the effects of CD40 ligation on the B-cell surface. He was subsequently a Senior Lecturer in Medical Oncology in the ICRF Cancer Medicine Research Unit, Leeds and took up the Chair of Medical Oncology in Southampton (UK) in 1998. He is responsible for bringing together a broad multidisciplinary group of basic, translational and clinical researchers, and linking the research of the academic unit to the extensive clinical practice in cancer treatment in the Southampton Cancer Centre. His research interests are in applied immunology and immunotherapy, lymphoma biology and clinical trials. He is Chief Investigator for lymphoma trials ranging from first in man novel antibody therapeutics to international randomized studies, and for the Cancer Research UK Stratified Medicine Programme. He was Chair of the UK National Cancer Research Institute Lymphoma Group from 2005 to 2011 and has been a member of national trials committees for the Medical Research Council, Cancer Research UK and Leukaemia and Lymphoma Research.

  7. Ovarian Cancer Classification based on Mass Spectrometry Analysis of Sera

    Directory of Open Access Journals (Sweden)

    Baolin Wu

    2006-01-01

    Full Text Available In our previous study [1], we have compared the performance of a number of widely used discrimination methods for classifying ovarian cancer using Matrix Assisted Laser Desorption Ionization (MALDI mass spectrometry data on serum samples obtained from Reflectron mode. Our results demonstrate good performance with a random forest classifier. In this follow-up study, to improve the molecular classification power of the MALDI platform for ovarian cancer disease, we expanded the mass range of the MS data by adding data acquired in Linear mode and evaluated the resultant decrease in classification error. A general statistical framework is proposed to obtain unbiased classification error estimates and to analyze the effects of sample size and number of selected m/z features on classification errors. We also emphasize the importance of combining biological knowledge and statistical analysis to obtain both biologically and statistically sound results. Our study shows improvement in classification accuracy upon expanding the mass range of the analysis. In order to obtain the best classification accuracies possible, we found that a relatively large training sample size is needed to obviate the sample variations. For the ovarian MS dataset that is the focus of the current study, our results show that approximately 20-40 m/z features are needed to achieve the best classification accuracy from MALDI-MS analysis of sera. Supplementary information can be found at http://bioinformatics.med.yale.edu/proteomics/BioSupp2.html.

  8. Association study of prostate cancer susceptibility variants with risks of invasive ovarian, breast, and colorectal cancer

    DEFF Research Database (Denmark)

    Song, H.; Koessler, T.; Ahmed, S.

    2008-01-01

    test of association was a comparison of genotype frequencies between cases and controls, and a test for trend stratified by study where appropriate. Genotype-specific odds ratios (OR) were estimated by logistic regression. SNP rs2660753 (chromosome 3p12) showed evidence of association with ovarian......Several prostate cancer susceptibility loci have recently been identified by genome-wide association studies. These loci are candidates for susceptibility to other epithelial cancers. The aim of this study was to test these tag single nucleotide polymorphisms (SNP) for association with invasive...... ovarian, colorectal, and breast cancer. Twelve prostate cancer-associated tag SNPs were genotyped in ovarian (2,087 cases/3,491 controls), colorectal (2,148 cases/2,265 controls) and breast (first set, 4,339 cases/4,552 controls; second set, 3,800 cases/3,995 controls) case-control studies. The primary...

  9. Mechanisms underlying p53 regulation of PIK3CA transcription in ovarian surface epithelium and in ovarian cancer.

    Science.gov (United States)

    Astanehe, Arezoo; Arenillas, David; Wasserman, Wyeth W; Leung, Peter C K; Dunn, Sandra E; Davies, Barry R; Mills, Gordon B; Auersperg, Nelly

    2008-03-01

    Inactivation of the transcription factor and tumor suppressor p53, and overexpression or mutational activation of PIK3CA, which encodes the p110alpha catalytic subunit of phosphatidylinositol-3-kinase (PI3K), are two of the most common deleterious genomic changes in cancer, including in ovarian carcinomas. We investigated molecular mechanisms underlying interactions between these two mediators and their possible roles in ovarian tumorigenesis. We identified two alternate PIK3CA promoters and showed direct binding of and transcriptional inhibition by p53 to one of these promoters. Conditional suppression of functional p53 increased p110alpha transcripts, protein levels and PI3K activity in immortalized, non-tumorigenic ovarian surface epithelial (OSE) cells, the precursors of ovarian carcinoma. Conversely, overexpression of p53 by adenoviral infection and activation of p53 by gamma-irradiation both diminished p110alpha protein levels in normal OSE and ovarian cancer cells. The demonstration that p53 binds directly to the PIK3CA promoter and inhibits its activity identifies a novel mechanism whereby these two mediators regulate cellular functions, and whereby inactivation of p53 and subsequent upregulation of PIK3CA might contribute to the pathophysiology of ovarian cancer.

  10. Cigarette smoking is associated with adverse survival among women with ovarian cancer

    DEFF Research Database (Denmark)

    Præstegaard, Camilla; Jensen, Allan; Jensen, Signe M

    2017-01-01

    Cigarette smoking is associated with an increased risk of developing mucinous ovarian tumors but whether it is associated with ovarian cancer survival overall or for the different histotypes is unestablished. Furthermore, it is unknown whether the association between cigarette smoking and surviva...... with localized than disseminated disease. The identification of cigarette smoking as a modifiable factor associated with survival has potential clinical importance as a focus area to improve ovarian cancer prognosis....

  11. Significance of determination of serum CA125 in patients with ovarian cancer

    International Nuclear Information System (INIS)

    Sun Jing; Zhou Xiaomei

    2002-01-01

    Objective: To study the clinical values of determining plasma CA125 in diagnosing and evaluating therapeutic effects in patients with ovarian cancer. Methods: RIA was used to measure serum CA125 in 108 patients with ovarian tumor (malignant: 56 cases, benign: 52 cases) and 38 controls. Results: Serum CA125 levels in 56 ovarian cancer patients were significantly higher than those in controls and patients with ovarian benign tumors; serum CA125 levels in 36 epithelial cancer patients were significantly higher than those in 20 non-epithelial cancer patients. There was no significant difference between patients with benign tumor and controls in serum CA125 possesses greater value in diagnosing ovarian cancer, specially in epithelial cancer and is a useful marker for evaluation of therapeutic effect and prognosis

  12. 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.

  13. 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.

  14. Epigenetic therapy for the treatment of epithelial ovarian cancer: A clinical review

    Directory of Open Access Journals (Sweden)

    Haller J. Smith

    2017-05-01

    Full Text Available Despite a good initial response to chemotherapy, the majority of patients with epithelial ovarian cancer will eventually recur and die of their disease. The introduction of targeted therapies to traditional chemotherapy regimens has done little to improve overall survival in women with ovarian cancer. It has become increasingly apparent that the cancer epigenome contributes significantly to the pathogenesis of ovarian cancer and may play an important role in cell proliferation, metastasis, chemoresistance, and immune tolerance. Epigenetic therapies such as DNA methyltransferase inhibitors and histone deacetylase inhibitors have the potential to reverse these epigenetic changes; however, more research is needed to determine how to incorporate these agents into clinical practice. In this review, we discuss the common epigenetic changes that occur in epithelial ovarian cancer, the current epigenetic therapies that may target these changes, and the clinical experience with epigenetic therapy for the treatment of epithelial ovarian cancer.

  15. Cancer-testis antigen expression is shared between epithelial ovarian cancer tumors.

    Science.gov (United States)

    Garcia-Soto, Arlene E; Schreiber, Taylor; Strbo, Natasa; Ganjei-Azar, Parvin; Miao, Feng; Koru-Sengul, Tulay; Simpkins, Fiona; Nieves-Neira, Wilberto; Lucci, Joseph; Podack, Eckhard R

    2017-06-01

    Cancer-testis (CT) antigens have been proposed as potential targets for cancer immunotherapy. Our objective was to evaluate the expression of a panel of CT antigens in epithelial ovarian cancer (EOC) tumor specimens, and to determine if antigen sharing occurs between tumors. RNA was isolated from EOC tumor specimens, EOC cell lines and benign ovarian tissue specimens. Real time-PCR analysis was performed to determine the expression level of 20 CT antigens. A total of 62 EOC specimens, 8 ovarian cancer cell lines and 3 benign ovarian tissues were evaluated for CT antigen expression. The majority of the specimens were: high grade (62%), serous (68%) and advanced stage (74%). 58 (95%) of the EOC tumors analyzed expressed at least one of the CT antigens evaluated. The mean number of CT antigen expressed was 4.5 (0-17). The most frequently expressed CT antigen was MAGE A4 (65%). Antigen sharing analysis showed the following: 9 tumors shared only one antigen with 62% of the evaluated specimens, while 37 tumors shared 4 or more antigens with 82%. 5 tumors expressed over 10 CT antigens, which were shared with 90% of the tumor panel. CT antigens are expressed in 95% of EOC tumor specimens. However, not a single antigen was universally expressed across all samples. The degree of antigen sharing between tumors increased with the total number of antigens expressed. These data suggest a multi-epitope approach for development of immunotherapy for ovarian cancer treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    BACKGROUND: We previously reported an association between rs2660753, a prostate cancer susceptibility polymorphism, and invasive epithelial ovarian cancer (EOC; OR = 1.2, 95% CI=1.0-1.4, P(trend) = 0.01) that showed a stronger association with the serous histological subtype (OR = 1.3, 95% CI = 1...

  17. 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.; et al.,

    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

  18. Ovarian Cancer: Still Possible After Hysterectomy?

    Science.gov (United States)

    ... peritoneum is a covering that lines the abdominal organs, and is close to the ovaries. Since the peritoneum and ovaries arise from the same tissues during embryonic development, it's possible that cancer could result from ...

  19. 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

  20. Carboplatin, Paclitaxel, Bevacizumab, and Veliparib in Treating Patients With Newly Diagnosed Stage II-IV Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cancer

    Science.gov (United States)

    2018-03-02

    Fallopian Tube Carcinosarcoma; Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Neoplasm; Fallopian Tube Transitional Cell Carcinoma; Ovarian Brenner Tumor; Ovarian Carcinosarcoma; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Seromucinous Tumor; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Primary Peritoneal Serous Adenocarcinoma; Stage IIA Fallopian Tube Cancer AJCC v6 and v7; Stage IIA Ovarian Cancer AJCC V6 and v7; Stage IIB Fallopian Tube Cancer AJCC v6 and v7; Stage IIB Ovarian Cancer AJCC v6 and v7; Stage IIC Fallopian Tube Cancer AJCC v6 and v7; Stage IIC Ovarian Cancer AJCC v6 and v7; Stage IIIA Fallopian Tube Cancer AJCC v7; Stage IIIA Ovarian Cancer AJCC v6 and v7; Stage IIIA Primary Peritoneal Cancer AJCC v7; Stage IIIB Fallopian Tube Cancer AJCC v7; Stage IIIB Ovarian Cancer AJCC v6 and v7; Stage IIIB Primary Peritoneal Cancer AJCC v7; Stage IIIC Fallopian Tube Cancer AJCC v7; Stage IIIC Ovarian Cancer AJCC v6 and v7; Stage IIIC Primary Peritoneal Cancer AJCC v7; Stage IV Fallopian Tube Cancer AJCC v6 and v7; Stage IV Ovarian Cancer AJCC v6 and v7; Stage IV Primary Peritoneal Cancer AJCC v7; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

  1. Time to stop ovarian cancer screening in BRCA1/2 mutation carriers?

    NARCIS (Netherlands)

    van der Velde, Nienke M.; Mourits, Marian J. E.; Arts, Henriette J. G.; de Vries, J.; Leegte, Beike K.; Dijkhuis, Grieteke; Osterwijk, Jan C.; de Bock, Geertruida H.

    2009-01-01

    Women at high risk of ovarian cancer (file to a genetic predisposition may opt for either surveillance or prophylactic bilateral salpingo-oophorectomy (pBSO). Main objective of our study was to determine the effectiveness of ovarian cancer screening in women with a BRCA1/2 mutation. We evaluated 241

  2. 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...

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

    Science.gov (United States)

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

    2015-01-01

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

  4. Abrogation of constitutive Stat3 activity circumvents cisplatin resistant ovarian cancer.

    Science.gov (United States)

    Ji, Teng; Gong, Danni; Han, Zhiqiang; Wei, Xiao; Yan, Yuting; Ye, Fei; Ding, Wencheng; Wang, Junnai; Xia, Xi; Li, Fei; Hu, Wencheng; Lu, Yunping; Wang, Shixuan; Zhou, Jianfeng; Ma, Ding; Gao, Qinglei

    2013-12-01

    The aim of the present study was to investigate the role of Stat3 in cisplatin resistant ovarian cancer. It was first demonstrated that higher activated Stat3 was detected in cisplatin-resistant ovarian cancer cell lines. To provide evidence that supported the hypothesis that phosphorylated-Stat3 expression may promote cisplatin resistance, ectopic Stat3 was expressed by IL-6 stimulation that partially abrogates Stat3, as opposed to the knock-down of Stat3 by specific siRNA that restores cisplatin sensitivity against ovarian cancer cells. This hypothesis was further confirmed by clinical tumor specimens of ovarian cancer obtained from patients with cisplatin-resistance. Based on these premises, Stattic, an effective small molecular inhibitor of Stat3, was used to inhibit Stat3 activation. The data presented here show that Stattic restored the sensitivity to cisplatin in chemoresistant ovarian cancer by significant reductions in the expression of the anti-apoptosis protein Bcl-2, Bcl-XL, Survivin protein and phosphorylated-Akt levels. Consistent with these observations, this experiment demonstrated the first evidence of Stattic circumvented cisplatin resistance of orthotopic xenograft ovarian cancer in vivo. Altogether, these findings emphasize the importance of Stat3 in cisplatin resistance in ovarian cancer and provide a further impetus to clinically evaluate biological modifiers that may circumvent cisplatin resistance in patients with chemoresistant ovarian cancer. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  5. 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,

  6. Mutational analysis of the BRCA1 gene in 30 Czech ovarian cancer ...

    Indian Academy of Sciences (India)

    Ovarian cancer is one of the most severe of oncological diseases. Inherited mutations in cancer susceptibility genes play a causal role in 5–10% of newly diagnosed tumours. BRCA1 and BRCA2 gene alterations are found in the majority of these cases. The aim of this study was to analyse the BRCA1 gene in the ovarian ...

  7. Height, body mass index, and ovarian cancer: A pooled analysis of 12 cohort studies

    NARCIS (Netherlands)

    Schouten, L.J.; Rivera, C.; Hunter, D.J.; Spiegelman, D.; Adami, H.-O.; Arslan, A.; Beeson, W.L.; Brandt, P.A. van den; Buring, J.E.; Folsom, A.R.; Fraser, G.E.; Freudenheim, J.L.; Goldbohm, R.A.; Hankinson, S.E.; Lacey Jr., J.V.; Leitzmann, M.; Lukanova, A.; Marshall, J.R.; Miller, A.B.; Patel, A.V.; Rodriguez, C.; Rohan, T.E.; Ross, J.A.; Wolk, A.; Zhang, S.M.; Smith-Warner, S.A.

    2008-01-01

    Background: Although many studies have investigated the association between anthropometry and ovarian cancer risk, results have been inconsistent. Methods: The associations of height, body mass index (BMI), and ovarian cancer risk were examined in a pooled analysis of primary data from 12

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

    International Nuclear Information System (INIS)

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

    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

  9. Mutational analysis of the BRCA1 gene in 30 Czech ovarian cancer ...

    Indian Academy of Sciences (India)

    Unknown

    Ovarian cancer is one of the most severe of oncological diseases. Inherited mutations in cancer susceptibility genes play a causal role in 5–10% of newly diagnosed tumours. BRCA1 and BRCA2 gene alterations are found in the major- ity of these cases. The aim of this study was to analyse the BRCA1 gene in the ovarian ...

  10. European Society of Gynaecologic Oncology Quality Indicators for Advanced Ovarian Cancer Surgery

    NARCIS (Netherlands)

    Querleu, Denis; Planchamp, Francois; Chiva, Luis; Fotopoulou, Christina; Barton, Desmond; Cibula, David; Aletti, Giovanni; Carinelli, Silvestro; Creutzberg, Carien; Davidson, Ben; Harter, Philip; Lundvall, Lene; Marth, Christian; Morice, Philippe; Rafii, Arash; Ray-Coquard, Isabelle; Rockall, Andrea; Sessa, Cristiana; van der Zee, Ate; Vergote, Ignace; du Bois, Andreas

    Objectives The surgical management of advanced ovarian cancer involves complex surgery. Implementation of a quality management program has a major impact on survival. The goal of this work was to develop a list of quality indicators (QIs) for advanced ovarian cancer surgery that can be used to audit

  11. 3 CFR 8407 - Proclamation 8407 of August 31, 2009. National Ovarian Cancer Awareness Month, 2009

    Science.gov (United States)

    2010-01-01

    .... National Ovarian Cancer Awareness Month helps educate women and men about the importance of knowing common... me by the Constitution and laws of the United States, do hereby proclaim September 2009 as National Ovarian Cancer Awareness Month. I encourage citizens, Government agencies, private businesses, nonprofit...

  12. SHP2 overexpression enhances the invasion and metastasis of ovarian cancer in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Hu ZQ

    2017-08-01

    Full Text Available ZhongQian Hu,1,* Jia Li,2,* Qi Gao,2,* Shuping Wei,1 Bin Yang1 1Department of Ultrasound, Jinling Clinical Medical College of Nanjing Medical University, Nanjing, China; 2Department of Ultrasound, Zhongda Hospital, Southeast University, Nanjing, China *These authors contributed equally to this work Purpose: SHP2 has roles in a variety of signal transduction pathways and in many important cellular processes, including proliferation, differentiation, movement regulation, and apoptosis. In addition, SHP2 expression is closely associated with multiple types of malignancies. In this study, we examined the role of SHP2 in epithelial ovarian cancer.Patients and methods: SHP2 expression in cancer and normal ovarian tissue specimens was evaluated by immunohistochemical staining and Western blot analyses. The correlation between the SHP2 expression level and clinicopathological features was analyzed. The role of SHP2 in epithelial ovarian cancer was evaluated by assessing SHP2 expression patterns in vitro and in vivo, and activation of the PI3K/AKT pathway was examined.Results: SHP2 is expressed at higher levels in ovarian cancer tissues than in normal ovarian tissues and in an ovarian cancer cell line than in a normal ovarian cell line. On the basis of these findings, SHP2 is overexpressed in ovarian cancer both in vitro and in vivo. In addition, SHP2 overexpression is associated with tumor stage and differentiation, enhanced cell proliferation and invasion, and tumorigenesis and metastasis.Conclusion: SHP2 overexpression enhances ovarian tumor proliferation and invasion by activating the PI3K-AKT axis, indicating that SHP2 potentially plays a direct role in the pathogenesis of ovarian epithelial cell cancer. These novel findings provide key insights that are applicable to basic cancer research and to the prevention and treatment of cancer. Keywords: ovarian tumor, SHP2, overexpression, proliferation, invasion, metastasis

  13. Effects of blood collection conditions on ovarian cancer serum markers.

    Directory of Open Access Journals (Sweden)

    Jason D Thorpe

    2007-12-01

    Full Text Available Evaluating diagnostic and early detection biomarkers requires comparing serum protein concentrations among biosamples ascertained from subjects with and without cancer. Efforts are generally made to standardize blood processing and storage conditions for cases and controls, but blood sample collection conditions cannot be completely controlled. For example, blood samples from cases are often obtained from persons aware of their diagnoses, and collected after fasting or in surgery, whereas blood samples from some controls may be obtained in different conditions, such as a clinic visit. By measuring the effects of differences in collection conditions on three different markers, we investigated the potential of these effects to bias validation studies.We analyzed serum concentrations of three previously studied putative ovarian cancer serum biomarkers-CA 125, Prolactin and MIF-in healthy women, women with ovarian cancer undergoing gynecologic surgery, women undergoing surgery for benign ovary pathology, and women undergoing surgery with pathologically normal ovaries. For women undergoing surgery, a blood sample was collected either in the clinic 1 to 39 days prior to surgery, or on the day of surgery after anesthesia was administered but prior to the surgical procedure, or both. We found that one marker, prolactin, was dramatically affected by collection conditions, while CA 125 and MIF were unaffected. Prolactin levels were not different between case and control groups after accounting for the conditions of sample collection, suggesting that sample ascertainment could explain some or all of the previously reported results about its potential as a biomarker for ovarian cancer.Biomarker validation studies should use standardized collection conditions, use multiple control groups, and/or collect samples from cases prior to influence of diagnosis whenever feasible to detect and correct for potential biases associated with sample collection.

  14. Cytoreductive surgery for stage IV epithelial ovarian cancer.

    Science.gov (United States)

    Zang, R Y; Zhang, Z Y; Cai, S M; Li, Z T; Chen, J; Tang, M Q; Liu, Q

    1999-12-01

    We tried to determine the role of cytoreductive surgery for stage IV epithelial ovarian cancer and in what conditions this surgical procedure could carry the best benefits. From January 1986 to December 1997, seventy-one of 73 patients with stage IV epithelial ovarian cancer who were treated in Cancer Hospital of Shanghai Medical University were retrospectively reviewed. Clinical information including age, grade, histology, presence of ascites, size of residual disease, site of extra-abdominal metastasis, whether initially presenting as metastatic disease or not, neo-adjuvant chemotherapy, platinum-based chemotherapy and second-line chemotherapy was obtained. Survival was calculated by life-table and survival curves were computed using the Kaplan-Meier method with differences in survival estimated by log-rank test. Independent prognostic factors were identified by Cox's proportional hazards regression model. The median age of the patients' population was 54 years (range 22-82), median follow-up time was 12 months (range 3 to 130) and estimated 5-year survival rate 6.1%. Thirty out of 71 (42.3%) patients were successfully debulked (< or = 1 cm) at the time of initial surgery. There was a significant difference in five-year survival rate between patients optimally (14.1%) vs suboptimally (0%) cytoreduced, with an estimated median survival in the optimal group of 23 months vs 9 months in the suboptimal group (P=0.0001, long-rank test). When the variables were factorized, only in patients with malignant pleural effusion or positive supraclavicular lymph nodes, optimal cytoreduction could get the greatest benefits. Multivariate analysis revealed that the size of residual disease and ascites were independent factors of survival. However, only ascites was the prognostic factor of progression-free survival. Optimal cytoreductive surgery is an important determinant of survival in women with stage IV epithelial ovarian cancer, mainly in those with malignant pleural effusion

  15. Identification of miRNA Signatures Associated with Epithelial Ovarian Cancer Chemoresistance with Further Biological and Functional Validation of Identified Key miRNAS

    Science.gov (United States)

    2016-04-01

    parameters in a cohort of ovarian tumor specimens from women diagnosed with stage III, grade 3, papillary serous adenocarcinoma all treated with...sensitize chemoresistant ovarian tumors to platinum treatment and inhibit ovarian cancer dissemination in a pre-clinical ovarian cancer mouse model. Our...chemoresistant cancer cells can sensitize chemoresistant ovarian tumors to cisplatin treatment and inhibit ovarian cancer dissemination in a pre

  16. Ovarian cancer risk, ALDH2 polymorphism and alcohol drinking: Asian data from the Ovarian Cancer Association Consortium.

    Science.gov (United States)

    Ugai, Tomotaka; Kelemen, Linda E; Mizuno, Mika; Ong, Jue-Sheng; Webb, Penelope M; Chenevix-Trench, Georgia; Wicklund, Kristine G; Doherty, Jennifer Anne; Rossing, Mary Anne; Thompson, Pamela J; Wilkens, Lynne R; Carney, Michael E; Goodman, Marc T; Schildkraut, Joellen M; Berchuck, Andrew; Cramer, Daniel W; Terry, Kathryn L; Cai, Hui; Shu, Xiao-Ou; Gao, Yu-Tang; Xiang, Yong-Bing; Van Den Berg, David; Pike, Malcom C; Wu, Anna H; Pearce, Celeste Leigh; Matsuo, Keitaro

    2018-02-01

    The aldehyde dehydrogenase 2 (ALDH2) polymorphism rs671 (Glu504Lys) causes ALDH2 inactivation and adverse acetaldehyde exposure among Asians, but little is known of the association between alcohol consumption and rs671 and ovarian cancer (OvCa) in Asians. We conducted a pooled analysis of Asian ancestry participants in the Ovarian Cancer Association Consortium. We included seven case-control studies and one cohort study comprising 460 invasive OvCa cases, 37 borderline mucinous OvCa and 1274 controls of Asian descent with information on recent alcohol consumption. Pooled odds ratios (OR) with 95% confidence intervals (CI) for OvCa risk associated with alcohol consumption, rs671 and their interaction were estimated using logistic regression models adjusted for potential confounders. No significant association was observed for daily alcohol intake with invasive OvCa (OR comparing any consumption to none = 0.83; 95% CI = 0.58-1.18) or with individual histotypes. A significant decreased risk was seen for carriers of one or both Lys alleles of rs671 for invasive mucinous OvCa (OR = 0.44; 95% CI = 0.20-0.97) and for invasive and borderline mucinous tumors combined (OR = 0.48; 95% CI = 0.26-0.89). No significant interaction was observed between alcohol consumption and rs671 genotypes. In conclusion, self-reported alcohol consumption at the quantities estimated was not associated with OvCa risk among Asians. Because the rs671 Lys allele causes ALDH2 inactivation leading to increased acetaldehyde exposure, the observed inverse genetic association with mucinous ovarian cancer is inferred to mean that alcohol intake may be a risk factor for this histotype. This association will require replication in a larger sample. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  17. Chemotherapy-induced hyaluronan production: a novel chemoresistance mechanism in ovarian cancer

    International Nuclear Information System (INIS)

    Ricciardelli, Carmela; Ween, Miranda P; Lokman, Noor A; Tan, Izza A; Pyragius, Carmen E; Oehler, Martin K

    2013-01-01

    Hyaluronan (HA) an important component of the extracellular matrix, has been linked to tumor progression and drug resistance in several malignancies. However, limited data is available for ovarian cancer. This study investigated the role of hyaluronan (HA) and a potential link between the HA-CD44 pathway and membrane ATP binding cassette (ABC) transporter proteins in ovarian cancer chemoresistance. We investigated the ability of HA to block the cytotoxic effects of the chemotherapy drug carboplatin, and to regulate the expression of ABC transporters in ovarian cancer cells. We also examined HA serum levels in ovarian cancer patients prior to and following chemotherapy and assessed its prognostic relevance. HA increased the survival of carboplatin treated ovarian cancer cells expressing the HA receptor, CD44 (OVCAR-5 and OV-90). Carboplatin significantly increased expression of HAS2, HAS3 and ABCC2 and HA secretion in ovarian cancer cell conditioned media. Serum HA levels were significantly increased in patients following platinum based chemotherapy and at both 1st and 2nd recurrence when compared with HA levels prior to treatment. High serum HA levels (>50 μg/ml) prior to chemotherapy treatment were associated with significantly reduced progression-free (P = 0.014) and overall survival (P = 0.036). HA production in ovarian cancer cells was increased in cancer tissues collected following chemotherapy treatment and at recurrence. Furthermore HA treatment significantly increased the expression of ABC drug transporters (ABCB3, ABCC1, ABCC2, and ABCC3), but only in ovarian cancer cells expressing CD44. The effects of HA and carboplatin on ABC transporter expression in ovarian cancer cells could be abrogated by HA oligomer treatment. Importantly, HA oligomers increased the sensitivity of chemoresistant SKOV3 cells to carboplatin. Our findings indicate that carboplatin chemotherapy induces HA production which can contribute to chemoresistance by regulating ABC

  18. 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.

  19. 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...... reductions, although typical oestrogen doses in the 1960s were more than double those in the 1980s. The incidence of mucinous tumours (12% of the total) seemed little affected by oral contraceptives, but otherwise the proportional risk reduction did not vary much between different histological types. In high...

  20. 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

    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......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...... carriers seemed to be greater among more recent users. Tubal ligation was associated with a reduced risk of ovarian cancer for BRCA1 carriers (hazard ratio, 0.42; 95% confidence intervals, 0.22-0.80; P = 0.008). The number of ovarian cancer cases in BRCA2 mutation carriers was too small to draw definitive...

  1. 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.

  2. 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....

  3. A Double Selection Approach to Achieve Specific Expression of Toxin Genes for Ovarian Cancer Gene Therapy

    National Research Council Canada - National Science Library

    Curiel, David T; Siegal, Gene; Wang, Minghui

    2005-01-01

    ... embodies the requisite properties of efficacy and specificity required for ovarian cancer gene therapy. This approach is based on targeting the delivered anti-cancer gene to tumor via two complimentary approaches...

  4. A Double Selection Approach to Achieve Specific Expression of Toxin Genes for Ovarian Cancer Gene Therapy

    National Research Council Canada - National Science Library

    Curiel, David T; Siegal, Gene; Wang, Minghui

    2006-01-01

    ... embodies the requisite properties of efficacy and specificity required for ovarian cancer gene therapy. This approach is based on targeting the delivered anti-cancer gene to tumor via two complimentary approaches...

  5. 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

  6. BRCA 1/2-Mutation Related and Sporadic Breast and Ovarian Cancers: More Alike than Different

    Science.gov (United States)

    Burgess, Melissa; Puhalla, Shannon

    2014-01-01

    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 and others have shown a number of genomic similarities between triple negative breast cancers (TNBCs) 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 TNBCs, 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. PMID:24579064

  7. Benefits and risks of ovarian function and reproduction for cancer development and prevention.

    Science.gov (United States)

    Schindler, Adolf E

    2011-12-01

    Ovarian function and menstrual cycle disturbances, pregnancy, and reproductive medicine procedures can either increase gynecological cancer risk or prevent cancer development. For ovarian cancer development, there are two hypotheses, which are connected with ovulation and gonadotropin secretion. Most of the ovarian cancers seem to be derived from displaced ovarian surfice epithelial cells. One year of ovulatory cycles increases the ovarian cancer risk by 6%. Ovulation between 22 and 29 years of age causes the highest risk increase per year. In contrast, progesterone or progestins appear to create protection. Lifestyle can affect or modify ovarian cancer risk. Breast cancer risk is very much related to age of menarche and menopause, pregnancy, and breast feeding. All of which are related to ovarian function and progestogenic impact that translates either into breast cancer risk increase or decrease. This is modified by body mass index, physical activity, and lifestyle in general. The risk of endometrial cancer is most closely related to endogenous progesterone during the menstrual cycle and pregnancy or by exogenous progestogens as in oral contraceptives. These effects are progestogen dose and time dependent. Endometrial cancer risk can also be increased by estrogen-producing tumors or long-term estrogen treatment.

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

    Directory of Open Access Journals (Sweden)

    Marianne Kramer

    2015-01-01

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

  9. 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 with

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

    DEFF Research Database (Denmark)

    Ding, Yuan C; McGuffog, Lesley; Healey, Sue

    2012-01-01

    We previously reported significant associations between genetic variants in insulin receptor substrate 1 (IRS1) and breast cancer risk in women carrying BRCA1 mutations. The objectives of this study were to investigate whether the IRS1 variants modified ovarian cancer risk and were associated wit...... with breast cancer risk in a larger cohort of BRCA1 and BRCA2 mutation carriers.......We previously reported significant associations between genetic variants in insulin receptor substrate 1 (IRS1) and breast cancer risk in women carrying BRCA1 mutations. The objectives of this study were to investigate whether the IRS1 variants modified ovarian cancer risk and were associated...

  11. 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.

  12. 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.

  13. 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.

  14. Lymphadenectomy in surgical stage I epithelial ovarian cancer

    DEFF Research Database (Denmark)

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

    2014-01-01

    2005-2011. SAMPLE: All women registered in the nationwide Danish Gynecologic Cancer Database from 1 January 2005 to 1 May 2011, presenting with a tumor macroscopically confined to the ovary without visible evidence of abdominal spread at the time of the initial exploration (surgical stage I). METHOD......: Descriptive and survival analyses of data from Danish Gynecologic Cancer Database. MAIN OUTCOME MEASURES: The annual proportion of women with surgical stage I disease who received lymphadenectomy and the survival in the two groups. RESULTS: Of 2361 women with epithelial ovarian cancer, 627 were identified...... with surgical stage I. Lymphadenectomy was performed in 216 women (34%) of whom 13 (6%) had lymph node metastases. At 5-year follow up 85% remained alive in the lymphadenectomy group compared with 80% in the control group (p = 0.064). The lymphadenectomy fraction increased from 24% in 2005 to 55% in 2011. When...

  15. Management of Hereditary Breast and Ovarian Cancer. The Asian Experience

    Directory of Open Access Journals (Sweden)

    Ava Kwong

    2017-02-01

    Full Text Available BRCA1/BRCA2 mutations are the most common high penetrant genes associated with an increased lifetime risk for hereditary breast and ovarian cancer (HBOC. Although genetic testing is standard of care in Western developed countries, there are still variations in availability of genetic testing and risk assessment for HBOC in Asia. Depending on the countries, there are variations in the clinical strategies and cancer management. The Asian BRCA Consortium has grouped together 14 Asian countries and reviewed genetic counselling/testing uptake rates and clinical management options in these countries. Moreover economic factors, healthcare and legal frameworks, and cultural issues affecting the genetic service availability in Asia were discussed. Mutation spectrum, and VUS rates and the increase use of NGS gene panel testing poses more decisional issues in the clinical management of Hereditary Breast cancer in Asia. These will be discussed. Keywords: BRCA1/BRCA2, germline, HBOC, Asia BRCA Consortium, NGS

  16. NuMA overexpression in epithelial ovarian cancer.

    Science.gov (United States)

    Brüning-Richardson, Anke; Bond, Jaqueline; Alsiary, Rawiah; Richardson, Julie; Cairns, David A; McCormac, Luci; Hutson, Richard; Burns, Philip A; Wilkinson, Nafisa; Hall, Geoff D; Morrison, Ewan E; Bell, Sandra M

    2012-01-01

    Highly aneuploid tumours are common in epithelial ovarian cancers (EOC). We investigated whether NuMA expression was associated with this phenomenon.NuMA protein levels in normal and tumour tissues, ovarian cell lines and primary cultures of malignant cells derived from ovarian ascitic fluids were analysed by Affymetrix microarray analysis, immunoblotting, immunohistochemistry (IHC) and immunofluorescence (IF), with results correlated to associated clinical data. Aneuploidy status in primary cultures was determined by FACS analysis.Affymetrix microarray data indicated that NuMA was overexpressed in tumour tissue, primary cultures and cell lines compared to normal ovarian tissue. IHC revealed low to weak NuMA expression in normal tissues. Expression was upregulated in tumours, with a significant association with disease stage in mucinous EOC subtypes (p = 0.009), lymph node involvement (p = 0.03) and patient age (p = 0.04). Additional discontinuous data analysis revealed that high NuMA levels in tumours decreased with grade (p = 0.02) but increased with disease stage (p = 0.04) in serous EOC. NuMA expression decreased in late disease stage 4 endometrioid EOCs. High NuMA levels decreased with increased tumour invasion in all subtypes (p = 0.03). IF of primary cultures revealed that high NuMA levels at mitotic spindle poles were significantly associated with a decreased proportion of cells in cytokinesis (p = 0.05), increased binucleation (p = 0.021) and multinucleation (p = 0.007), and aneuploidy (p = 0.008).NuMA is highly expressed in EOC tumours and high NuMA levels correlate with increases in mitotic defects and aneuploidy in primary cultures.

  17. NuMA overexpression in epithelial ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Anke Brüning-Richardson

    Full Text Available Highly aneuploid tumours are common in epithelial ovarian cancers (EOC. We investigated whether NuMA expression was associated with this phenomenon.NuMA protein levels in normal and tumour tissues, ovarian cell lines and primary cultures of malignant cells derived from ovarian ascitic fluids were analysed by Affymetrix microarray analysis, immunoblotting, immunohistochemistry (IHC and immunofluorescence (IF, with results correlated to associated clinical data. Aneuploidy status in primary cultures was determined by FACS analysis.Affymetrix microarray data indicated that NuMA was overexpressed in tumour tissue, primary cultures and cell lines compared to normal ovarian tissue. IHC revealed low to weak NuMA expression in normal tissues. Expression was upregulated in tumours, with a significant association with disease stage in mucinous EOC subtypes (p = 0.009, lymph node involvement (p = 0.03 and patient age (p = 0.04. Additional discontinuous data analysis revealed that high NuMA levels in tumours decreased with grade (p = 0.02 but increased with disease stage (p = 0.04 in serous EOC. NuMA expression decreased in late disease stage 4 endometrioid EOCs. High NuMA levels decreased with increased tumour invasion in all subtypes (p = 0.03. IF of primary cultures revealed that high NuMA levels at mitotic spindle poles were significantly associated with a decreased proportion of cells in cytokinesis (p = 0.05, increased binucleation (p = 0.021 and multinucleation (p = 0.007, and aneuploidy (p = 0.008.NuMA is highly expressed in EOC tumours and high NuMA levels correlate with increases in mitotic defects and aneuploidy in primary cultures.

  18. Crowdsourcing awareness: exploration of the ovarian cancer knowledge gap through Amazon Mechanical Turk.

    Directory of Open Access Journals (Sweden)

    Rebecca R Carter

    Full Text Available BACKGROUND: Ovarian cancer is the most lethal gynecologic disease in the United States, with more women dying from this cancer than all gynecological cancers combined. Ovarian cancer has been termed the "silent killer" because some patients do not show clear symptoms at an early stage. Currently, there is a lack of approved and effective early diagnostic tools for ovarian cancer. There is also an apparent severe knowledge gap of ovarian cancer in general and of its indicative symptoms among both public and many health professionals. These factors have significantly contributed to the late stage diagnosis of most ovarian cancer patients (63% are diagnosed at Stage III or above, where the 5-year survival rate is less than 30%. The paucity of knowledge concerning ovarian cancer in the United States is unknown. METHODS: The present investigation examined current public awareness and knowledge about ovarian cancer. The study implemented design strategies to develop an unbiased survey with quality control measures, including the modern application of multiple statistical analyses. The survey assessed a reasonable proxy of the US population by crowdsourcing participants through the online task marketplace Amazon Mechanical Turk, at a highly condensed rate of cost and time compared to traditional recruitment methods. CONCLUSION: Knowledge of ovarian cancer was compared to that of breast cancer using repeated measures, bias control and other quality control measures in the survey design. Analyses included multinomial logistic regression and categorical data analysis procedures such as correspondence analysis, among other statistics. We confirmed the relatively poor public knowledge of ovarian cancer among the US population. The simple, yet novel design should set an example for designing surveys to obtain quality data via Amazon Mechanical Turk with the associated analyses.

  19. MTHFR polymorphisms in relation to ovarian cancer risk

    OpenAIRE

    Terry, Kathryn Lynne; Tworoger, Shelley Slate; Goode, Ellen L.; Gates, Margaret A.; Titus-Ernstoff, Linda; Kelemen, Linda E.; Sellers, Thomas A.; Hankinson, Susan Elizabeth; Cramer, Daniel William

    2010-01-01

    Objective Folate has been hypothesized to influence carcinogenesis due to its dual role in DNA methylation, which regulates gene expression, and synthesis of purine and thymidylate, which is vital for DNA repair. Thus, we examined ovarian cancer risk in relation to two functional polymorphisms (C677T and A1298C) in the MTHFR gene. Methods We genotyped the C677T (rs1801133) and A1298C (rs1801131) MTHFR polymorphisms in 1642 cases and 2068 controls from three studies, the New Englan...

  20. Deciphering the Adaptive Immune Response to Ovarian Cancer

    Science.gov (United States)

    2013-10-01

    Inc, Cary, NC, 1989–2012. 35. Ashburner M, Ball CA, Blake JA, et al . Gene ontology: tool for the unification of biology. The Gene Ontology Consortium...Prognosis in Ovarian Cancer Julie S. Nielsen1,3, Rob A. Sahota1, Katy Milne1, Sara E. Kost1,2, Nancy J. Nesslinger1, Peter H. Watson1,2,4, and Brad H...deLeeuw1,2, Sara E. Kost1,2, Juzer A. Kakal1, and Brad H. Nelson1,2,3 Abstract CD8þ tumor-infiltrating lymphocytes (TIL) are associated with survival in

  1. Biological Basis for Chemoprevention of Ovarian Cancer

    Science.gov (United States)

    2006-10-01

    During the study interview a thorough history of the menstrual cycle and reproductive experiences of the study participants is obtained from each...cancer.24 The scope of vitamin D deficiency extends well beyond the elderly however, as widespread vitamin D deficiency is common in adolescents and...gene in ras-transformed keratinocytes demonstrates that locally produced 1alpha,25-dihydroxyvitamin D3 suppresses growth and induces differentiation in

  2. Mutation or Loss of p53 Differentially Modifies TGFβ Action in Ovarian Cancer

    Science.gov (United States)

    Ó hAinmhire, Eoghainín; Quartuccio, Suzanne M.; Cheng, Whay; Ahmed, Roshan A.; King, Shelby M.; Burdette, Joanna E.

    2014-01-01

    Ovarian cancer is the most lethal gynecological disease affecting women in the US. The Cancer Genome Atlas Network identified p53 mutations in 96% of high-grade serous ovarian carcinomas, demonstrating its critical role. Additionally, the Transforming Growth Factor Beta (TGFβ) pathway is dysfunctional in various malignancies, including ovarian cancer. This study investigated how expression of wild-type, mutant, or the absence of p53 alters ovarian cancer cell response to TGFβ signaling, as well as the response of the ovarian surface epithelium and the fallopian tube epithelium to TGFβ. Only ovarian cancer cells expressing wild-type p53 were growth inhibited by TGFβ, while ovarian cancer cells that were mutant or null p53 were not. TGFβ induced migration in p53 null SKOV3 cells, which was not observed in SKOV3 cells with stable expression of mutant p53 R273H. Knockdown of wild-type p53 in the OVCA 420 ovarian cancer cells enhanced cell migration in response to TGFβ. Increased protein expression of DKK1 and TMEPAI, two pro-invasive genes with enhanced expression in late stage metastatic ovarian cancer, was observed in p53 knockdown and null cells, while cells stably expressing mutant p53 demonstrated lower DKK1 and TMEPAI induction. Expression of mutant p53 or loss of p53 permit continued proliferation of ovarian cancer cell lines in the presence of TGFβ; however, cells expressing mutant p53 exhibit reduced migration and decreased protein levels of DKK1 and TMEPAI. PMID:24586866

  3. Anti-cancer effect of Scutellaria baicalensis in combination with cisplatin in human ovarian cancer cell.

    Science.gov (United States)

    Choi, Bo Yoon; Joo, Jong Cheon; Lee, Yeon Kyu; Jang, Ik-Soon; Park, Soo Jung; Park, Yoon Jung

    2017-05-25

    Ovarian cancer is one of the major causes of death among females in worldwide. Cisplatin is a primary anti-cancer drug against ovarian cancer, but the recurrent tumors after treatment frequently show acquired chemoresistance. Extract of Scutellaria baicalensis (SbE) has been reported to have functional compounds including baicalin, which has anti-cancer effects. However, the anti-cancer effects of SbE in ovarian cancer and its underlying mechanisms are elusive. We investigated that the effects of SbE and/or cisplatin on cell death in the cisplatin sensitive ovarian cancer cell line A2780 (CSC) and the counterpart cell line that has cisplatin resistance (CRC). Molecular mechanisms of the effects, focusing on apoptosis and autophagy, were examined. Treatment of cisplatin or SbE reduced cell viability significantly in CSC and too much lesser extent in CRC. Cisplatin-induced cell death in CSC was mediated by p53-induced apoptosis acompanied by expresson of damage-regulated autophagy modulator (DRAM). In CRC, decreased DRAM expression (p cisplatin resistance. Treatment of SbE also induced cell death in CSC by p53-dependent apoptosis, not in CRC. Autophagy was not induced by neither cisplatin nor SbE. Intriguingly, the combinational treatment of SbE and cisplatin significantly decreased cell viability in CRC. The cell death was mediated by autophagy with increased expression of Atg5 and Atg12 (p cisplatin was effective in CRC, leading to cell death via Beclin1-independent autophagy, suggesting that SbE treatment in combination with cisplatin has a potential as a chemotherapeutic agent in cisplatin-resistant ovarian cancer.

  4. Increased expression of Nlp, a potential oncogene in ovarian cancer, and its implication in carcinogenesis.

    Science.gov (United States)

    Qu, Danni; Qu, Hongyan; Fu, Ming; Zhao, Xuelian; Liu, Rong; Sui, Lihua; Zhan, Qimin

    2008-08-01

    Nlp (Ninein-like protein), a novel centrosome protein involved in microtubule nucleation, has been studied extensively in our laboratory, and its overexpression has been found in some human tumors. To understand the role of Nlp in human ovarian cancer development, we studied the correlation of Nlp expression with clinicopathological parameters and survival in epithelial ovarian cancer, and the impact of Nlp overexpression on ovarian cancer cells. Nlp expression in normal, borderline, benign and malignant epithelial ovarian tissues was examined by immunohistochemistry. The correlation between Nlp expression and tumor grade, FIGO stage and histological type was also evaluated. Survival was calculated using Kaplan-Meier estimates. Cell proliferation and apoptosis were assayed after stable transfection of pEGFP-C3-Nlp or empty vector in human ovarian cancer cell line SKOV3. Nlp was positive in 1 of 10 (10%) normal ovarian tissues, 5 of 34 (14.7%) benign tumors, 9 of 26 (34.6%) borderline tumors and 73 of 131 (56.0%) ovarian tumors. Nlp immunoreactivity intensity significantly correlated with tumor grade, but not with FIGO stage or histological type. Kaplan-Meier curves showed that Nlp overexpression was marginally associated with decreased overall survival. Overexpression of Nlp enhanced proliferation and inhibited apoptosis induced by paclitaxel in the SKOV3 cell line. Overexpression of Nlp in ovarian tumors raises the possibility that Nlp may play a role in ovarian carcinogenesis.

  5. Modulators of Response to Tumor Necrosis-related Apoptosis Inducing Ligand (TRAIL) Therapy in Ovarian Cancer

    Science.gov (United States)

    2011-05-01

    Poor Survival. Cancer Res 67: 3036–3042. 22. Fulda S, Scaffidi C, Pietsch T, Krammer PH, Peter ME, et al. (1998) Activation of the CD95 (APO-1/Fas...in ovarian carcinoma causes resistance to TRAIL-mediated apoptosis and is associated with poor survival. Cancer Res 2007; 67:3036-42. 19. Yu Y ...ovarian cancer in remission. 315 Therapeutic efficacy of folate receptor α blockade with MORAb-003 in ovarian cancer W. A. Spannuth1, Y . G. Lin1, W. M

  6. Expanded metabolomics approach to profiling endogenous carbohydrates in the serum of ovarian cancer patients.

    Science.gov (United States)

    Cheng, Yu; Li, Li; Zhu, Bangjie; Liu, Feng; Wang, Yan; Gu, Xue; Yan, Chao

    2016-01-01

    We applied hydrophilic interaction liquid chromatography coupled with tandem mass spectrometry to the quantitative analysis of serum from 58 women, including ovarian cancer patients, ovarian benign tumor patients, and healthy controls. All of these ovarian cancer and ovarian benign tumor patients have elevated cancer antigen 125, which makes them clinically difficult to differentiate the malignant from the benign. All of the 16 endogenous carbohydrates were quantitatively detected in the human sera, of which, eight endogenous carbohydrates were significantly different (P-value carbohydrates in the expanded metabolomics approach after the global metabolic profiling are characterized and are potential biomarkers for the early diagnosis of ovarian cancer. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. MHC class I-presented tumor antigens identified in ovarian cancer by immunoproteomic analysis are targets for T-cell responses against breast and ovarian cancer.

    Science.gov (United States)

    Morse, Michael A; Secord, Angeles A; Blackwell, Kimberly; Hobeika, Amy C; Sinnathamby, Gomathinayagam; Osada, Takuya; Hafner, Julie; Philip, Mohan; Clay, Timothy M; Lyerly, H Kim; Philip, Ramila

    2011-05-15

    The purpose of this study is to test whether peptide epitopes chosen from among those naturally processed and overpresented within MHC molecules by malignant, but not normal cells, when formulated into cancer vaccines, could activate antitumor T-cell responses in humans. Mixtures of human leukocyte antigen A2 (HLA-A2)-binding ovarian cancer-associated peptides were used to activate naive T cells to generate antigen-specific T cells that could recognize ovarian and breast cancers in vitro. Combinations of these peptides (0.3 mg of each peptide or 1 mg of each peptide) were formulated into vaccines in conjunction with Montanide ISA-51 and granulocyte monocyte colony stimulating factor which were used to vaccinate patients with ovarian and breast cancer without evidence of clinical disease in parallel pilot clinical trials. T cells specific for individual peptides could be generated in vitro by using mixtures of peptides, and these T cells recognized ovarian and breast cancers but not nonmalignant cells. Patient vaccinations were well tolerated with the exception of local erythema and induration at the injection site. Nine of the 14 vaccinated patients responded immunologically to their vaccine by inducing peptide-specific T-cell responses that were capable of recognizing HLA-matched breast and ovarian cancer cells. Mixtures of specific peptides identified as naturally presented on cancer cells and capable of activating tumor-specific T cells in vitro also initiate or augment immune responses toward solid tumors in cancer patients. ©2011 AACR.

  8. 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.

  9. Prognostic implication of the metastatic lesion-to-ovarian cancer standardised uptake value ratio in advanced serous epithelial ovarian cancer

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-11-15

    To evaluate the prognostic value of metabolic activity of metastatic lesions measured by {sup 18}F-flurodeoxyglucose ({sup 18}F-FDG) uptake on preoperative positron emission tomography/computed tomography (PET/CT) in patients with advanced serous epithelial ovarian cancer (EOC). Clinico-pathological variables and PET/CT parameters such as the maximum standardised uptake value of the ovarian cancer (SUV{sub ovary}), metastatic lesions (SUV{sub meta}), and the metastatic lesion-to-ovarian cancer standardised uptake value ratio (SUV{sub meta}/SUV{sub ovary}) were assessed in International Federation of Gynaecology and Obstetrics (FIGO) stage III, IV patients. Clinico-pathological data were retrospectively reviewed for 94 eligible patients. The median progression-free survival (PFS) was 18.5 months (range, 6-90 months), and 57 (60.6%) patients experienced recurrence. Older age [P = 0.017, hazard ratio (HR) 1.036, 95% CI 1.006-1.066], residual disease after surgery (P = 0.024, HR 1.907, 95% CI 1.087-3.346), and high SUV{sub meta}/SUV{sub ovary} (P = 0.019, HR 2.321, 95% CI 1.148-4.692) were independent risk factors of recurrence. Patients with high SUV{sub meta}/SUV{sub ovary} showed a significantly worse PFS than those with low SUV{sub meta}/SUV{sub ovary} (P = 0.007, log-rank test). Preoperative SUV{sub meta}/SUV{sub ovary} was significantly associated with recurrence and has an incremental prognostic value for PFS in patients with advanced serous EOC. (orig.)

  10. [Biological characteristics of an established model of ovarian cancer in mice and its homologous cell lines].

    Science.gov (United States)

    Zhang, Zheng-Mao; Zhang, Chao; Zhang, Feng-Hua; Shan, Bao-En; Nakagawa, Shinsaku

    2006-06-01

    There are no specific methods for early diagnosis of ovarian cancer, recurrence prevention and drug-resistance. The experimental mouse model of ovarian cancer could help to reveal the biological and genetic features of ovarian cancer, and provide rational basis for further intervention strategy. This study was to establish a model of ovarian cancer in mice and homologous cell line, and analyze its biological characteristics. Ovarian cancer was developed in 8-week-old female F1 (C57BL/6N x C3H/He) mice by a single whole-body neutron irradiation of 2.7 Gy from a (252)Cf source. A metastatic cell line was established through serial subcutaneous transplantation of the primary tumor for 11 generations, and then tumor cells were transferred to in vitro cultivation. These cells were cloned for more than 6 months. The biological characteristics of the tumors and the homologous cell line were determined by cellular and molecular biological techniques. The grafted tumors in mice were successively passaged for 11 generations with a successful inoculation rate of 96% during 23 months. A tumor cell line OV99 isolated from the grafted tumors was established after 6 months and grew steadily. Morphologic characters and ultrastructures of OV99 cells were accorded with those of ovarian cancer epithelia. The chromosomal analysis of OV99 cells revealed aneuploid pattern of 76 chromosomes. Flow cytometry (FCM) and reverse transcription-polymerase chain reaction (RT-PCR) showed same features between OV99 cells and positive control ovarian cancer cell line OVHM, including distribution of cell cycle, rapid growth rate and the expression of P21, P185, P53, proliferating nuclear cell antigen (PCNA) and Cyclin D proteins, and MAGE-1 and MAGE-3 mRNA. Establishment of the ovarian carcinoma animal model in mice and OV99, a cell line owns biologic characteristics of ovarian cancer cells, provides experimental materials for further investigation of ovarian carcinoma.

  11. Protein markers of cancer-associated fibroblasts and tumor-initiating cells reveal subpopulations in freshly isolated ovarian cancer ascites

    Directory of Open Access Journals (Sweden)

    Wintzell My

    2012-08-01

    Full Text Available Abstract Background In ovarian cancer, massive intraperitoneal dissemination is due to exfoliated tumor cells in ascites. Tumor-initiating cells (TICs or cancer stem cells and cells showing epithelial-mesenchymal-transition (EMT are particularly implicated. Spontaneous spherical cell aggregates are sometimes observed, but although similar to those formed by TICs in vitro, their significance is unclear. Methods Cells freshly isolated from malignant ascites were separated into sphere samples (S-type samples, n=9 and monolayer-forming single-cell suspensions (M-type, n=18. Using western blot, these were then compared for expression of protein markers of EMT, TIC, and of cancer-associated fibroblasts (CAFs. Results S-type cells differed significantly from M-type by expressing high levels of E-cadherin and no or little vimentin, integrin-β3 or stem cell transcription factor Oct-4A. By contrast, M-type samples were enriched for CD44, Oct-4A and for CAF markers. Independently of M- and S-type, there was a strong correlation between TIC markers Nanog and EpCAM. The CAF marker α-SMA correlated with clinical stage IV. This is the first report on CAF markers in malignant ascites and on SUMOylation of Oct-4A in ovarian cancer. Conclusions In addition to demonstrating potentially high levels of TICs in ascites, the results suggest that the S-type population is the less tumorigenic one. Nanoghigh/EpCAMhigh samples represent a TIC subset which may be either M- or S-type, and which is separate from the CD44high/Oct-4Ahigh subset observed only in M-type samples. This demonstrates a heterogeneity in TIC populations in vivo which has practical implications for TIC isolation based on cell sorting. The biological heterogeneity will need to be addressed in future therapeutical strategies.

  12. Protein markers of cancer-associated fibroblasts and tumor-initiating cells reveal subpopulations in freshly isolated ovarian cancer ascites

    International Nuclear Information System (INIS)

    Wintzell, My; Hjerpe, Elisabet; Åvall Lundqvist, Elisabeth; Shoshan, Maria

    2012-01-01

    In ovarian cancer, massive intraperitoneal dissemination is due to exfoliated tumor cells in ascites. Tumor-initiating cells (TICs or cancer stem cells) and cells showing epithelial-mesenchymal-transition (EMT) are particularly implicated. Spontaneous spherical cell aggregates are sometimes observed, but although similar to those formed by TICs in vitro, their significance is unclear. Cells freshly isolated from malignant ascites were separated into sphere samples (S-type samples, n=9) and monolayer-forming single-cell suspensions (M-type, n=18). Using western blot, these were then compared for expression of protein markers of EMT, TIC, and of cancer-associated fibroblasts (CAFs). S-type cells differed significantly from M-type by expressing high levels of E-cadherin and no or little vimentin, integrin-β3 or stem cell transcription factor Oct-4A. By contrast, M-type samples were enriched for CD44, Oct-4A and for CAF markers. Independently of M- and S-type, there was a strong correlation between TIC markers Nanog and EpCAM. The CAF marker α-SMA correlated with clinical stage IV. This is the first report on CAF markers in malignant ascites and on SUMOylation of Oct-4A in ovarian cancer. In addition to demonstrating potentially high levels of TICs in ascites, the results suggest that the S-type population is the less tumorigenic one. Nanog high /EpCAM high samples represent a TIC subset which may be either M- or S-type, and which is separate from the CD44 high /Oct-4A high subset observed only in M-type samples. This demonstrates a heterogeneity in TIC populations in vivo which has practical implications for TIC isolation based on cell sorting. The biological heterogeneity will need to be addressed in future therapeutical strategies

  13. Characterization of human mesothelin transcripts in ovarian and pancreatic cancer

    International Nuclear Information System (INIS)

    Muminova, Zhanat E; Strong, Theresa V; Shaw, Denise R

    2004-01-01

    Mesothelin is an attractive target for cancer immunotherapy due to its restricted expression in normal tissues and high level expression in several tumor types including ovarian and pancreatic adenocarcinomas. Three mesothelin transcript variants have been reported, but their relative expression in normal tissues and tumors has been poorly characterized. The goal of the present study was to clarify which mesothelin transcript variants are commonly expressed in human tumors. Human genomic and EST nucleotide sequences in the public databases were used to evaluate sequences reported for the three mesothelin transcript variants in silico. Subsequently, RNA samples from normal ovary, ovarian and pancreatic carcinoma cell lines, and primary ovarian tumors were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and nucleotide sequencing to directly identify expressed transcripts. In silico comparisons of genomic DNA sequences with available EST sequences supported expression of mesothelin transcript variants 1 and 3, but there were no sequence matches for transcript variant 2. Newly-derived nucleotide sequences of RT-PCR products from tissues and cell lines corresponded to mesothelin transcript variant 1. Mesothelin transcript variant 2 was not detected. Transcript variant 3 was observed as a small percentage of total mesothelin amplification products from all studied cell lines and tissues. Fractionation of nuclear and cytoplasmic RNA indicated that variant 3 was present primarily in the nuclear fraction. Thus, mesothelin transcript variant 3 may represent incompletely processed hnRNA. Mesothelin transcript variant 1 represents the predominant mature mRNA species expressed by both normal and tumor cells. This conclusion should be important for future development of cancer immunotherapies, diagnostic tests, and gene microarray studies targeting mesothelin

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

    Directory of Open Access Journals (Sweden)

    Matyunina Lilya V

    2009-12-01

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

  15. Research progress in applying proteomics technology to explore early diagnosis biomarkers of breast cancer, lung cancer and ovarian cancer.

    Science.gov (United States)

    Luo, Lu; Dong, Li-You; Yan, Qi-Gui; Cao, San-Jie; Wen, Xin-Tian; Huang, Yong; Huang, Xiao-Bo; Wu, Rui; Ma, Xiao-Ping

    2014-01-01

    According to the China tumor registry 2013 annual report , breast cancer, lung cancer, and ovarian cancer are three common cancers in China nowadays, with high mortality due to the absence of early diagnosis technology. However, proteomics has been widespreadly implanted into every field of life science and medicine as an important part of post-genomics era research. The development of theory and technology in proteomics has provided new ideas and research fields for cancer research. Proteomics can be used not only for elucidating the mechanisms of carcinogenesis focussing on whole proteins of the tissue or cell, but also seeking the biomarkers for diagnosis and therapy of cancer. In this review, we introduce proteomics principles, covering current technology used in exploring early diagnosis biomarkers of breast cancer, lung cancer and ovarian cancer.

  16. 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

  17. The anti-tumor effect and bioactive phytochemicals of Hedyotis diffusa willd on ovarian cancer cells.

    Science.gov (United States)

    Zhang, Lin; Zhang, Jing; Qi, Bing; Jiang, Guoqiang; Liu, Jia; Zhang, Pei; Ma, Yuan; Li, Weiling

    2016-11-04

    Hedyotis diffusa willd (HDW) is a widely used medicinal herb in China. It processed various medicinal properties including antioxidative, anti-inflamatory and anti-cancer effects. This study aimed to investigate the anti-tumor effects of HDW on ovarian cancer cells and the underlying mechanisms as well as identify the bioactive compounds. Effects of HDW on the viability of ovarian cancer A2780 cells were detected by MTT assay. Apoptosis was detected by cell morphologic observation through DAPI staining and flow cytometry analysis. The migration of ovarian cancer cells which exposed to HDW were detected by wound healing and transwell assays. The protein levels of caspase 3/9, Bcl-2 and MMP-2/9 in human ovarian cancer cells treated with HDW were assessed by western blotting analysis. The potential bioactive compounds were characterized by HPLC-Q-TOF-MS. HDW significantly inhibited the growth of A2780 ovarian cancer cells and induced apoptosis. The induction of apoptosis by HDW was associated with down-regulation of anti-apoptotic protein Bcl-2 and the activation of caspase 3/9. Wound healing and transwell chamber assays indicated HDW suppressed the migration of ovarian cancer cells. HDW dramatically decreased MMP-2/9 expression. A HPLC-Q-TOF-MS analysis of HDW indicated the presence of 13 flavonoids compounds and one anthraquinone compound, which may contribute to the anticancer activity of the HDW. HDW effectively restricted the growth of ovarian cancer cells and induced apoptosis through the mitochondria-associated apoptotic pathway. Furthermore, HDW suppressed the migration of ovarian cancer cells through down-regulation of MMP-2 and MMP-9 expression. These results showed that HDW hold potential therapeutic effect for ovarian cancer patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. 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...

  19. Expression of FK506 binding protein 65 (FKBP65) is decreased in epithelial ovarian cancer cells compared to benign tumor cells and to ovarian epithelium

    DEFF Research Database (Denmark)

    Henriksen, Rudi; Sørensen, Flemming Brandt; Ørntoft, Torben Falck

    2011-01-01

    to be followed by a strongly increased risk of ovarian cysts. We performed the present study to reveal how FKBP65 is expressed in the ovary and in ovarian tumors and to see if this expression might be related to ovarian tumor development, a relationship we have found in colorectal cancer. Biopsies from...... prospectively collected samples from ovaries and benign, borderline, and invasive ovarian tumors were analyzed for expression of FKBP65 by immunohistochemistry. The expression was compared to survival and several clinicopathological parameters. FKBP65 is strongly expressed in ovarian epithelium and in benign...

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

    Directory of Open Access Journals (Sweden)

    Narod Steven

    2004-02-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Alternative tumor markers in the diagnosis of ovarian cancer.

    Science.gov (United States)

    Karakaya, Burcu Kısa; Başer, Eralp; Bildacı, Berk; Cömert, Esra Çabuk; Bayraktar, Nilufer; Dursun, Polat; Kuşçu, Esra; Ayhan, Ali

    2016-01-01

    The aim of the study was to assess the usefulness of various tumor markers (CA125, HE4, bcl2) measured in serum, urine and saliva in the differential diagnosis of adnexal masses. Our study was conducted at the Başkent University Medical School, Department of Obstetrics and Gynecology, Ankara, Turkey, between November 2010 and March 2011. Fifty patients with a suspicion of malignant adnexal mass and 30 controls were included in the study. Serum and urine CA-125, HE4, and bcl2 levels were evaluated for their role in the diagnosis of epithelial ovarian cancer (EOC). Serum CA-125 and HE4 levels, and urine HE4 levels were significantly higher in malignant cases as compared to controls (p saliva and urine were similar in malignant cases and controls (p > 0.05). We demonstrated that serum CA125, serum HE4 and urine HE4 levels were elevated in patients with ovarian cancer. These findings should be assessed in future studies with larger sample sizes in order to reach more definite conclusions.

  3. Delphinidin inhibits BDNF-induced migration and invasion in SKOV3 ovarian cancer cells.

    Science.gov (United States)

    Lim, Won-Chul; Kim, Hyunhee; Kim, Young-Joo; Park, Seung-Ho; Song, Ji-Hye; Lee, Ki Heon; Lee, In Ho; Lee, Yoo-Kyung; So, Kyeong A; Choi, Kyung-Chul; Ko, Hyeonseok

    2017-12-01

    Brain-derived neurotrophic factor (BDNF), the TrkB ligand, is associated with aggressive malignant behavior, including migration and invasion, in tumor cells and a poor prognosis in patients with various types of cancer. Delphinidin is a diphenylpropane-based polyphenolic ring structure-harboring compound, which exhibits a wide range of pharmacological activities, anti-tumor, anti-oxidant, anti-inflammatory, anti-angiogenic and anti-mutagenic activity. However, the possible role of delphinidin in the cancer migration and invasion is unclear. We investigated the suppressive effect of delphinidin on the cancer migration and invasion. Thus, we found that BDNF enhanced cancer migration and invasion in SKOV3 ovarian cancer cell. To exam the inhibitory role of delphinidin in SKOV3 ovarian cancer migration and invasion, we investigated the use of delphinidin as inhibitors of BDNF-induced motility and invasiveness in SKOV3 ovarian cancer cells in vitro. Here, we found that delphinidin prominently inhibited the BDNF-induced increase in cell migration and invasion of SKOV3 ovarian cancer cells. Furthermore, delphinidin remarkably inhibited BDNF-stimulated expression of MMP-2 and MMP-9. Also, delphinidin antagonized the phosphorylation of Akt and nuclear translocation of NF-κB permitted by the BDNF in SKOV3 ovarian cancer cells. Taken together, our findings provide new evidence that delphinidin suppressed the BDNF-induced ovarian cancer migration and invasion through decreasing of Akt activation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Potent cytotoxic effects of Calomeria amaranthoides on ovarian cancers

    Directory of Open Access Journals (Sweden)

    van Haard Paul MM

    2011-03-01

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

  5. Illness representations and distress in women undergoing screening for familial ovarian cancer.

    Science.gov (United States)

    Lancastle, D; Brain, K; Phelps, C

    2011-12-01

    Women with a familial or genetic predisposition to ovarian cancer are at significantly increased risk of developing the disease, and this warrants effective risk management strategies. A clinical trial of ovarian cancer screening (OCS) is being conducted to establish the effectiveness of this risk management strategy. This article reports data from its psychological partner study which aims to evaluate the psychological effects of OCS. Leventhal's Self-Regulatory Model provided the theoretical framework for understanding emotional responses to OCS. The revised Illness Perceptions Questionnaire (IPQ-R) is based on this model and the IPQ-R, adapted to the risk of ovarian cancer, was completed by women (N = 1999) prior to screening. The original IPQ-R factor structure was not replicated but IPQ-R variables explained 14.70% of the variance in women's ovarian cancer-specific distress after controlling for age, general anxiety and depression. Negative emotional representations of ovarian cancer risk and general anxiety were moderately associated with greater ovarian cancer-specific distress whereas cognitive illness representations were weakly related to ovarian cancer-specific distress. Further analyses of data from the ongoing psychological evaluation are needed to determine the predictive utility of IPQ-R variables in explaining distress during OCS.

  6. Association of oral contraceptive use, other contraceptive methods, and infertility with ovarian cancer risk.

    Science.gov (United States)

    Tworoger, Shelley S; Fairfield, Kathleen M; Colditz, Graham A; Rosner, Bernard A; Hankinson, Susan E

    2007-10-15

    Although oral contraceptives are protective for ovarian cancer, it is unclear how long this protection persists. The authors prospectively assessed this question as well as associations of other, less studied contraceptive methods (tubal ligation, rhythm method, diaphragm, condoms, intrauterine device, foam, spousal vasectomy) and infertility with ovarian cancer risk among 107,900 participants in the US Nurses' Health Study. During 28 years of follow-up (1976-2004), 612 cases of invasive epithelial ovarian cancer were confirmed. Duration of oral contraceptive use was inversely associated with risk (p-trend = 0.02), but no clear trend was observed for years since last use. However, for women using oral contraceptives for >5 years, the rate ratio for ovarian cancer for 20 years since last use (rate ratio (RR) = 0.92, 95% CI: 0.61, 1.39). Tubal ligation (RR = 0.66, 95% CI: 0.50, 0.87) was associated with decreased ovarian cancer risk, whereas intrauterine device use (RR = 1.76, 95% CI: 1.08, 2.85) and infertility (RR = 1.36, 95% CI: 1.07, 1.75) were associated with an increased risk. Results suggest that the beneficial effect of oral contraceptives on ovarian cancer risk attenuates after 20 years since last use. Furthermore, tubal ligation, intrauterine device use, and infertility were associated with ovarian cancer risk.

  7. 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.)

  8. Distribution of Microsatellite instability in Danish ovarian tumor patients and the prognostic value in ovarian cancer patients

    DEFF Research Database (Denmark)

    Begum, F.D.; Kjaer, S.K.; Blaakaer, J.

    2008-01-01

    The repeated frequency of microsatellite instability (MSI) in ovarian cancer (OC) ranges from 0% to 50%. Most MSI studies including OC patients have involved relatively small number of tumors, a wide range of different MSI markers, different patient characteristics, and varying criteria for defin...

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

    OpenAIRE

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

    2016-01-01

    Ovarian cancer survival remains poor despite recent advances in our understanding of genetic profiles. Unfortunately, the majority of ovarian cancer patients have recurrent disease after chemotherapy and lack other treatment options. Wnt signalling has been extensively implicated in cancer progression and chemoresistance. Therefore, we investigated the previously described Wnt receptors ROR1 and ROR2 as regulators of epithelial-to-mesenchymal transition (EMT) in a clinically relevant cell lin...

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

    Science.gov (United States)

    2015-10-01

    survival is only 27% (2). Epithelial ovarian cancer (EOC) has no specific symptoms, and no screening or early detection measures have been adopted ...results may not be generalizable to other racial or ethnic groups or to other countries. Our model was developed and internally validated among...significance of IL-6 and IL-8 ascites levels in ovarian cancer patients. BMC Cancer. 2011;11:210. 14. Lo CW, Chen MW, Hsiao M, et al. IL-6 trans -signaling

  11. Involvement of MKP-1 and Bcl-2 in acquired cisplatin resistance in ovarian cancer cells

    OpenAIRE

    Wang, Juan; Zhou, Jun-Ying; Zhang, Lianfeng; Wu, Gen Sheng

    2009-01-01

    Although cisplatin is a very effective anticancer agent against several types of cancer including ovarian cancer, the mechanisms of acquired resistance are not fully understood. By chronically exposing cisplatin to ovarian cancer cell lines, we established two cisplatin-resistant cell lines OV433 and tOV112D. Our results indicate that the mechanisms underlying their cisplatin resistance are distinct. In OV433 cells, cisplatin resistance is associated with increased expression of mitogen-activ...

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

    DEFF Research Database (Denmark)

    Domanska, K; Malander, S; Måsbäck, A

    2007-01-01

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

  13. The contribution of BRCA1 and BRCA2 to ovarian cancer.

    Science.gov (United States)

    Ramus, Susan J; Gayther, Simon A

    2009-04-01

    Germline mutations of the BRCA1 and BRCA2 genes confer a high life-time risk of ovarian cancer. They represent the most significant and well characterised genetic risk factors so far identified for the disease. The frequency with which BRCA1/2 mutations occur in families containing multiple cases of ovarian cancer or breast and ovarian cancer, and in population-based ovarian cancer series varies geographically and between different ethnic groups. There are differences in the frequency of common mutations and in the presence of specific founder mutations in different populations. BRCA1 and BRCA2 are responsible for half of all families containing two or more ovarian cancer cases. In population-based studies, BRCA1 and BRCA2 mutations are present in 5-15% of all ovarian cancer cases. Often, individuals in which mutations are identified in unselected cases have no family history of either ovarian or breast cancer. The ability to identify BRCA1/2 mutations has been one of the few major success stories over the last few years in the clinical management of ovarian cancer. Currently, unaffected individuals can be screened for mutations if they have a family history of the disease. If a mutation is identified in the family, and if an individual is found be a mutation carrier, they can be offered clinical intervention strategies that can dramatically reduce their ovarian cancer risks. In some populations with frequent founder mutations screening may not be dependent on whether a mutation is identified in an affected relative.

  14. CA-125 level as a prognostic indicator in type I and type II epithelial ovarian cancer.

    Science.gov (United States)

    Chen, Xiaoxiang; Zhang, Jing; Cheng, Wenjun; Chang, Doo Young; Huang, Jianfei; Wang, Xuan; Jia, Lizhou; Rosen, Daniel G; Zhang, Wei; Yang, Da; Gershenson, David M; Sood, Anil K; Bast, Robert C; Liu, Jinsong

    2013-06-01

    Most patients with epithelial ovarian cancer achieve a complete clinical remission (CCR) with normal CA-125 but will still relapse and die from their disease. The present study was designed to determine whether CA-125 levels before, during, and after primary treatment provide prognostic information for both type I and type II ovarian cancer. In this retrospective study, we identified 410 patients with epithelial ovarian cancer who had achieved a CCR between 1984 and 2011. A Cox proportional hazards model and log-rank test were used to assess associations between the nadir CA-125, histotype, and prognosis. The baseline serum CA-125 concentration was higher in patients with type II ovarian cancer than in those with type I ovarian cancer (P CA-125 was an independent predictor of progression-free survival (PFS; P CA-125 of 10 U/mL or less and 13.6 and 64.6 months in those with CA-125 of 11 to 35 U/mL, respectively (P = 0.01 and P = 0.002, respectively). Histotype was an independent predictor of PFS (P = 0.041): the PFS and OS durations of the patients with type I ovarian cancer were longer than those of the patients with type II ovarian cancer (P CA-125 and histotype are predictive of PFS and OS durations in patients with ovarian cancers who experienced a CCR. Progression-free survival and OS durations were shorter in the patients with CA-125 levels of 11 to 35 U/mL and type II disease than in those with CA-125 levels of 10 U/mL or less and type I ovarian cancer.

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

    Science.gov (United States)

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

    2012-01-01

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

  16. IMP3 expression in human ovarian cancer is associated with improved survival

    DEFF Research Database (Denmark)

    Noske, Aurelia; Faggad, Areeg; Wirtz, Ralph

    2009-01-01

    investigated the expression of IMP3 at protein and mRNA levels in a cohort of primary ovarian carcinomas and in 11 ovarian cancer cell lines. Western blot analysis revealed an expression of IMP3 in all ovarian cancer cell lines and immunohistochemistry demonstrated a positive cytoplasmic staining in 32 of 68...... carcinomas (47%). In contrast, epithelium of borderline tumors, as well as, benign ovarian lesions and normal ovaries exhibited only weak or no IMP3 expression. In univariate Kaplan-Meier analysis, IMP3 protein expression was significantly associated with better overall survival (P=0.048). To confirm......The insulin-like growth factor-II mRNA-binding protein IMP3 plays an important role in embryogenesis and recent reports suggest an involvement in tumorigenesis. Although IMP3 expression has been well studied in mouse and human fetal and adult gonads, its role in ovarian cancer is unknown. We...

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    OBJECTIVE: Transcriptional profiling of epithelial ovarian cancer has revealed molecular subtypes correlating to biological and clinical features. We aimed to determine gene expression differences between malignant, benign and borderline serous ovarian tumors, and investigate similarities...... with the well-established intrinsic molecular subtypes of breast cancer. METHODS: Global gene expression profiling using Illumina's HT12 Bead Arrays was applied to 59 fresh-frozen serous ovarian malignant, benign and borderline tumors. Nearest centroid classification was performed applying previously published...... expressed between benign and malignant serous ovarian tumors, with cell cycle processes enriched in the malignant subgroup. Borderline tumors were split between the two clusters. Significant correlations between the malignant serous tumors and the highly aggressive ovarian cancer signatures, and the basal...

  18. Radiogenomics of High-Grade Serous Ovarian Cancer: Multireader Multi-Institutional Study from the Cancer Genome Atlas Ovarian Cancer Imaging Research Group.

    Science.gov (United States)

    Vargas, Hebert Alberto; Huang, Erich P; Lakhman, Yulia; Ippolito, Joseph E; Bhosale, Priya; Mellnick, Vincent; Shinagare, Atul B; Anello, Maria; Kirby, Justin; Fevrier-Sullivan, Brenda; Freymann, John; Jaffe, C Carl; Sala, Evis

    2017-11-01

    Purpose To evaluate interradiologist agreement on assessments of computed tomography (CT) imaging features of high-grade serous ovarian cancer (HGSOC), to assess their associations with time-to-disease progression (TTP) and HGSOC transcriptomic profiles (Classification of Ovarian Cancer [CLOVAR]), and to develop an imaging-based risk score system to predict TTP and CLOVAR profiles. Materials and Methods This study was a multireader, multi-institutional, institutional review board-approved, HIPAA-compliant retrospective analysis of 92 patients with HGSOC (median age, 61 years) with abdominopelvic CT before primary cytoreductive surgery available through the Cancer Imaging Archive. Eight radiologists from the Cancer Genome Atlas Ovarian Cancer Imaging Research Group developed and independently recorded the following CT features: characteristics of primary ovarian mass(es), presence of definable mesenteric implants and infiltration, presence of other implants, presence and distribution of peritoneal spread, presence and size of pleural effusions and ascites, lymphadenopathy, and distant metastases. Interobserver agreement for CT features was assessed, as were univariate and multivariate associations with TTP and CLOVAR mesenchymal profile (worst prognosis). Results Interobserver agreement for some features was strong (eg, α = .78 for pleural effusion and ascites) but was lower for others (eg, α = .08 for intraparenchymal splenic metastases). Presence of peritoneal disease in the right upper quadrant (P = .0003), supradiaphragmatic lymphadenopathy (P = .0004), more peritoneal disease sites (P = .0006), and nonvisualization of a discrete ovarian mass (P = .0037) were associated with shorter TTP. More peritoneal disease sites (P = .0025) and presence of pouch of Douglas implants (P = .0045) were associated with CLOVAR mesenchymal profile. Combinations of imaging features contained predictive signal for TTP (concordance index = 0.658; P = .0006) and CLOVAR profile (mean

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

    Science.gov (United States)

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

    2016-01-01

    Inflammatory cytokines, like tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6), are elevated in ovarian cancer. Differences in cytokine expression by histologic subytpe or ovarian cancer risk factors can provide useful insight into ovarian cancer risk and etiology. We used ribonucleic acid (RNA) in-situ hybridization to assess TNF-α and IL-6 expression on tissue microarray slides from 78 epithelial ovarian carcinomas (51 serous, 12 endometrioid, 7 clear cell, 2 mucinous, 6 other) from a population-based case control study. Cytokine expression was scored semi-quantitatively and odds ratios (OR) and 95% confidence intervals (CI) were calculated using polytomous logistic regression. TNF-α was expressed in 46% of the tumors while sparse IL-6 expression was seen only 18% of the tumors. For both markers, expression was most common in high grade serous carcinomas followed by endometrioid carcinomas. Parity was associated with a reduced risk of TNF-α positive (OR=0.3, 95% CI: 0.1-0.7 for 3 or more children versus none) but not TNF-α negative tumors (p-heterogeneity=0.02). In contrast, current smoking was associated with a nearly three fold increase in risk of TNF-α negative (OR=2.8, 95% CI: 1.2, 6.6) but not TNF-α positive tumors (p-heterogeneity = 0.06). Our data suggests that TNF-α expression in ovarian carcinoma varies by histologic subtype and provides some support for the role of inflammation in ovarian carcinogenesis. The novel associations detected in our study need to be validated in a larger cohort of patients in future studies. PMID:27068525

  20. Setting the Threshold for Surgical Prevention in Women at Increased Risk of Ovarian Cancer.

    Science.gov (United States)

    Manchanda, Ranjit; Menon, Usha

    2018-01-01

    The number of ovarian cancer cases is predicted to rise by 14% in Europe and 55% worldwide over the next 2 decades. The current absence of a screening program, rising drug/treatment costs, and only marginal improvements in survival seen over the past 30 years suggest the need for maximizing primary surgical prevention to reduce the burden of ovarian cancer. Primary surgical prevention through risk-reducing salpingo-oophorectomy (RRSO) is well established as the most effective method for preventing ovarian cancer. In the UK, it has traditionally been offered to high-risk women (>10% lifetime risk of ovarian cancer) who have completed their family. The cost-effectiveness of RRSO in BRCA1/BRCA2 carriers older than 35 years is well established. Recently, RRSO has been shown to be cost-effective in postmenopausal women at lifetime ovarian cancer risks of 5% or greater and in premenopausal women at lifetime risks greater than 4%. The acceptability, uptake, and satisfaction with RRSO at these intermediate-risk levels remain to be established. Prospective outcome data on risk-reducing salpingectomy and delayed-oophorectomy for preventing ovarian cancer is lacking, and hence, this is best offered for primary prevention within the context and safe environment of a clinical trial. An estimated 63% of ovarian cancers occur in women with greater than 4% lifetime risk and 53% in those with 5% or greater lifetime-risk. Risk-reducing salpingo-oophorectomy can be offered for primary surgical prevention to women at intermediate risk levels (4%-5% to 10%). This includes unaffected women who have completed their family and have RAD51C, RAD51D, or BRIP1 gene mutations; first-degree relatives of women with invasive epithelial ovarian cancer; BRCA mutation-negative women from high-risk breast-and-ovarian cancer or ovarian-cancer-only families. In those with BRCA1, RAD51C/RAD51D/MMR mutations and the occasional families with a history of ovarian cancer in their 40s, surgery needs to be

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    samples were aliquotted and frozen at -80 degrees until the time of analysis. The urine was fractionated using equalizer bead technology and then analyzed with surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. Biomarkers were purified and identified using combinations...... of chromatographic techniques and tandem mass spectrometry. RESULTS: Benign and malignant ovarian cancer cases were compared; 21 significantly different peaks (p...OBJECTIVE: To examine whether urine can be used to measure specific ovarian cancer proteomic profiles and whether one peak alone or in combination with other peaks or CA125 has the sensitivity and specificity to discriminate between ovarian cancer pelvic mass and benign pelvic mass. METHODS...

  2. The role of pemetrexed in recurrent epithelial ovarian cancer: a scoping review

    Directory of Open Access Journals (Sweden)

    Michael Roche

    2018-03-01

    Full Text Available Ovarian cancer is the leading cause of mortality among gynecologic malignancies, with most cases diagnosed at an advanced stage. Despite an initial response, most develop a recurrence and subsequent resistance to standard therapies. Pemetrexed (AlimtaTM is a new generation multi-targeted antifolate initially approved for the treatment of malignant pleural mesothelioma. In recent years, it has shown promise in the treatment of recurrent epithelial ovarian cancer. In this review, we outline the current literature and discuss the future of pemetrexed in the setting of recurrent epithelial ovarian cancer.

  3. Increased risk of second cancer among patients with ovarian borderline tumors.

    Science.gov (United States)

    Bouchardy, Christine; Fernandez, Sarah; Merglen, Arnaud; Usel, Massimo; Fioretta, Gérald; Rapiti, Elisabetta; Schubert, Hyma; Pelte, Marie-Françoise; Chappuis, Pierre O; Vlastos, Georges

    2008-05-01

    Several studies have demonstrated a higher risk of colorectal and breast cancers subsequent to invasive ovarian cancer. Such risk has not been investigated for ovarian borderline tumors. We aim to evaluate the risk of subsequent cancer occurrence among patients with borderline ovarian tumors in a population-based setting. We identified 171 patients with a diagnosis of borderline ovarian tumors recorded at the Geneva Cancer Registry, Switzerland. We calculated age and period standardized incidence ratios (SIR) of second tumor occurrence by dividing the number of observed cases by the number of expected cases in the cohort, using cancer incidence rates of the general female population. The risk of developing second cancer was 1.85-fold (95% Confidence Interval [CI]: 1.10-2.92, n=16) higher among women with borderline ovarian tumors compared to that expected in the general population. The excess of risk primarily concerned colorectal cancer (SIR: 3.97, CI: 1.38-12.95, n=5) and breast cancer (SIR: 2.09, CI: 0.84-4.31, n=7), but the latter result was not statistically significant (p=0.09). The increased risk of developing second cancer was mainly observed among patients diagnosed with ovarian borderline tumors occurring before the age of 50. These results were not explained by surveillance bias or by metastasis from one site to another. Women with ovarian borderline tumors have an increased risk of developing secondary cancer, particularly colorectal cancer. These results point to potential common risk factors for these tumors and ask for close surveillance of patients with borderline ovarian tumors.

  4. Emergence of p53 mutant cisplatin-resistant ovarian carcinoma cells following drug exposure: spontaneously mutant selection.

    Science.gov (United States)

    Righetti, S C; Perego, P; Corna, E; Pierotti, M A; Zunino, F

    1999-07-01

    We have previously shown that p53 mutations are associated with cisplatin resistance in ovarian carcinoma IGROV-1/Pt 1 cells. The relationship between p53 status and the development of resistance has not been completely elucidated; in particular, the biological mechanisms behind the acquired drug-resistant p53-mutant phenotype were not clearly explained. Thus, in this study, we investigated whether the p53 mutations found in IGROV-1/Pt 1 cells (270 and 282 codons) resulted from selection, under the selective pressure of the cytotoxic treatment, of a spontaneously mutant cell population preexistent in the cisplatin-sensitive parental cell line (IGROV-1) or were induced by drug (genotoxic) treatment. For this purpose, an allele-specific PCR approach was used. Primers carrying the desired mutations (T-->A codon 270, C-->T codon 282) in the 3' terminus, and the corresponding wild-type primers were used to amplify genomic DNA from the original IGROV-1 cell line used to select the mutant IGROV-1/Pt 1. To increase sensitivity, we hybridized blots of the PCRs with the radiolabeled PCR fragment from IGROV-1/Pt 1. Amplification was obtained for IGROV-1 DNA with the mutated allele-specific primers, indicating the preexistence of a mutated population in the IGROV-1 cell line. Titration experiments suggested that the frequency of the mutated alleles was PCR analysis of the IGROV-1/Pt 0.1 cells, which are less resistant to cisplatin than IGROV-1/Pt 1 cells and which carry both mutant and wild-type p53 alleles with a wild-type predominance, suggested a progressive selection of the mutant population by cisplatin treatment. This is the first observation that indicates that a subpopulation of p53 mutant cells can occasionally be selected by cisplatin treatment. Thus, considering the susceptibility to spontaneous mutations of the p53 gene in advanced ovarian carcinoma, the selection process resulting in emergence of p53 mutant tumors is a possible origin of resistance of ovarian

  5. 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,

  6. Germline mutations in BRCA1 and BRCA2 in epithelial ovarian cancer patients in Brazil

    NARCIS (Netherlands)

    Maistro, Simone; Teixeira, Natalia; Encinas, Giselly; Hirata Katayama, Maria Lucia; Tavares Niewiadonski, Vivian Dionisio; Cabral, Larissa Garcia; Ribeiro, Roberto Marques; Gaburo Junior, Nelson; Ribeiro Chaves de Gouvea, Ana Carolina; Carraro, Dirce Maria; Sabino, Ester Cerdeira; Estevez Diz, Maria del Pilar; Chammas, Roger; de Bock, Geertruida Hendrika; Azevedo Koike Folgueira, Maria Aparecida

    2016-01-01

    Background: Approximately 8-15% epithelial ovarian cancer patients are BRCA1 or BRCA2 germline mutation carriers. Brazilian inhabitants may have peculiar genetic characteristics associated with ethnic diversity, and studies focusing on the entire BRCA1/BRCA2 gene sequencing in Brazilian ovarian

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

    DEFF Research Database (Denmark)

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

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

  8. 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

  9. Prognostic significance of CA 125 and TPS levels after 3 chemotherapy courses in ovarian cancer patients

    NARCIS (Netherlands)

    van Dalen, A; Favier, J; Burges, A; Hasholzner, U; de Bruijn, HWA; Dobler-Girdziunaite, D; Dombi, VH; Fink, D; Giai, M; McGing, P; Harlozinska, A; Kainz, C; Markowska, J; Molina, R; Sturgeon, C; Bowman, A; Einarsson, R

    2000-01-01

    Objective. To evaluate the prognostic significance of and predictive value for survival of CA 125 and TPS levels after three chemotherapy courses in ovarian cancer patients. Methods. We analyzed in a prospective multicenter study the 1- and 2-year overall survival (OS) in ovarian carcinoma patients.

  10. Relevance of HLA-DP/DQ and ICAM-1 SNPs among Ovarian Cancer Patients.

    Science.gov (United States)

    Ghazy, Amany A; El-Etreby, Nour M

    2016-01-01

    Ovarian cancer is one of the most lethal gynecological malignancies and the fifth leading cause of cancer deaths among women. The high mortality rate is largely attributed to its diagnosis in advanced stages. Poor prognosis of ovarian cancer is usually due to the lack of specific or effective screening and diagnostic methods for identifying early-stage disease. Our study aimed to study the role of HLA-DP, HLA-DQ, and ICAM-1 SNPs in diagnosis and/or prognosis of ovarian tumors. The current study was conducted on 60 patients with ovarian tumors (benign, borderline, and malignant) and 20 healthy volunteers. Genotyping of HLA-DP rs3077, HLA-DQ rs3920, and ICAM-1 rs1437 SNPs was done using 5' nuclease assay. We found significant association of HLA-DP rs3077 AA, HLA-DQ rs3920 GG, ICAM-1 rs1437 CC, and CT genotypes with increased risk of ovarian cancer (OR = 43.5, 6, 25, and 2.6, respectively). In addition, HLA-DQ rs3920 and ICAM-1 rs1437 alleles vary significantly among different types of ovarian cancer (P = 0.003 and 0.001, respectively). HLA-DP rs3077, HLA-DQ rs3920, and ICAM-1 rs1437 SNPs could help in the diagnosis and prognosis of ovarian cancer.

  11. Vitamin D receptor rs2228570 polymorphism and invasive ovarian carcinoma risk: pooled analysis in five studies within the Ovarian Cancer Association Consortium

    DEFF Research Database (Denmark)

    Lurie, Galina; Wilkens, Lynne R; Thompson, Pamela J

    2011-01-01

    The association of invasive ovarian carcinoma risk with the functional polymorphism rs2228570 (aka rs10735810; FokI polymorphism) in the vitamin D receptor (VDR) gene was examined in 1820 white non-Hispanic cases and 3479 controls in a pooled analysis of five population-based case-control studies...... within the Ovarian Cancer Association Consortium. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression. Carriers of the rare T allele were at increased risk of ovarian carcinoma compared to women with the CC genotype in all studies combined; each...... analysis provides further evidence that the VDR rs2228570 polymorphism might influence ovarian cancer susceptibility....

  12. Ovarian cancer with metastatic inguinal lymphadenopathy: A case series and literature review

    Directory of Open Access Journals (Sweden)

    Islam H. Metwally

    2017-06-01

    Full Text Available Background: Ovarian cancer is the 4th commonest cancer among Egyptian women. It can spread through 3 different lymphatic pathways to para-aortic/paracaval lymph nodes, to pelvic lymph nodes and only occasionally through the round ligament of the uterus to the inguinal nodes. These rare cases are staged IVb on FIGO system. Presentation: We present a series of 4 cases of ovarian cancer metastasizing to inguinal nodes. The literature review revealed only 17 published similar cases. Management controversies as well as prognosis are discussed in our study. Conclusion: Inguinal metastasis from ovarian cancer seems more frequent than previously thought. Examination of inguinal region should be mandatory in all cases diagnosed with ovarian cancer.

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

    DEFF Research Database (Denmark)

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

    2009-01-01

    The p53 protein is critical for multiple cellular functions including cell growth and DNA repair. We assessed whether polymorphisms in the region encoding TP53 were associated with risk of invasive ovarian cancer. The study population includes a total of 5,206 invasive ovarian cancer cases (2......,829 of which were serous) and 8,790 controls from 13 case-control or nested case-control studies participating in the Ovarian Cancer Association Consortium (OCAC). Three of the studies performed independent discovery investigations involving genotyping of up to 23 single nucleotide polymorphisms (SNP.......07-1.57) and rs12951053 (median per allele OR, 1.19; 95% PI, 1.01-1.38). Analyses of other histologic subtypes suggested similar associations with endometrioid but not with mucinous or clear cell cancers. This large study provides statistical evidence for a small increase in risk of ovarian cancer associated...

  14. The psychosocial transition associated with spontaneous 46,XX primary ovarian insufficiency: illness uncertainty, stigma, goal flexibility, and purpose in life as factors in emotional health.

    Science.gov (United States)

    Davis, Mary; Ventura, June L; Wieners, Mary; Covington, Sharon N; Vanderhoof, Vien H; Ryan, Mary E; Koziol, Deloris E; Popat, Vaishali B; Nelson, Lawrence M

    2010-05-01

    To examine factors associated with emotional well-being in women with spontaneous primary ovarian insufficiency. Cross-sectional and case-control study. Clinical research center, national U.S. health research facility. Women diagnosed with spontaneous 46,XX primary ovarian insufficiency (n = 100) at a mean age of 32.4 years and healthy control women of similar age (n = 60). Administration of validated self-reporting instruments. Illness uncertainty, stigma, goal disengagement/re-engagement, purpose in life, Positive and Negative Affect Schedule, Center of Epidemiologic Studies Depression Scale, State-Trait Anxiety Inventory. Compared with controls, women with spontaneous primary ovarian insufficiency scored adversely on all measures of affect. Illness uncertainty and purpose in life were significant independent factors associated with anxiety (R(2) = 0.47), stigma and purpose in life were the significant independent factors associated with depression (R(2) = 0.51), and goal re-engagement and purpose in life were significantly and independently associated with positive affect (R(2) = 0.43). This evidence supports the need for prospective studies. Our findings are consistent with the hypothesis that clinicians could improve the emotional well-being of their patients with primary ovarian insufficiency by [1] informing them better about their condition, [2] helping them to feel less stigmatized by the disorder, and [3] assisting them in developing alternative goals with regard to family planning as well as other goals. Published by Elsevier Inc.

  15. Precursors of ovarian cancer in the fallopian tube: serous tubal intraepithelial carcinoma--an update.

    Science.gov (United States)

    Zeppernick, Felix; Meinhold-Heerlein, Ivo; Shih, Ie-Ming

    2015-01-01

    Ovarian tumors comprise a wide variety of entities. The largest group, epithelial ovarian carcinoma, can be classified into two main groups, type I and type II tumors. Recent advances in the understanding of ovarian cancer development have resulted in the finding of 'serous tubal intraepithelial carcinoma', which is believed to represent the precursor lesion in high-grade serous ovarian carcinoma. In this review, lines of evidence for this are discussed and possible future implications for clinical and research settings are outlined. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

  16. CA 125 radioimmunoassay for the diagnosis and assessment of the effectiveness of therapy of ovarian cancer

    International Nuclear Information System (INIS)

    Sagan, D.L.; Chebotareva, Eh.D.; Evtushenko, G.V.

    1989-01-01

    The paper is concerned with the results of CA-125 radioimmunoassay in 163 patients (584 tests) with benign and malignant ovarian diseases and other small pelvic diseases which were diagnosed before operation as ovarian tumors. CA-125 radioimmunoassay can be used in combination with other methods for investigation of patients with suspected ovarian cancer and for differential diagnosis of malignant ovarian tumors to distinguish them from other malignant tumors of the small pelvis. The investigation of CA-125 indices in the course of disease was indicative of the effectiveness of antitumor therapy

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

    DEFF Research Database (Denmark)

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

    2010-01-01

    Aberrant glycosylation is a well-described hallmark of cancer. In a previous ovarian cancer case control study that examined polymorphisms in 26 glycosylation-associated genes, we found strong statistical evidence (P = 0.00017) that women who inherited two copies of a single-nucleotide polymorphism...... in the UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltransferase, GALNT1, had decreased ovarian cancer risk. The current study attempted to replicate this observation. The GALNT1 single-nucleotide polymorphism rs17647532 was genotyped in 6,965 cases and 8,377 controls from 14 studies forming...... the Ovarian Cancer Association Consortium. The fixed effects estimate per rs17647532 allele was null (odds ratio, 0.99; 95% confidence interval, 0.92-1.07). When a recessive model was fit, the results were unchanged. Test for heterogeneity of the odds ratios revealed consistency across the 14 replication...

  18. Longitudinal evaluation of CA-125 velocity and prediction of ovarian cancer.

    Science.gov (United States)

    Xu, Jian-Lun; Commins, John; Partridge, Edward; Riley, Thomas L; Prorok, Philip C; Johnson, Christine C; Buys, Saundra S

    2012-04-01

    To determine whether CA-125 velocity is a statistically significant predictor of ovarian cancer and develop a classification rule to screen for ovarian cancer. In the ovarian component of the PLCO cancer screening trial, 28,038 women aged 55-74 had at least two CA-125 screening tests. Ovarian cancer was diagnosed in 72 (0.26%) women. A multiple logistic regression model was developed to evaluate CA-125 velocity and other related covariates as predictors of ovarian cancer. Predictive accuracy was assessed by the concordance index and measures of discrimination and calibration while the fit of the model was assessed by the Hosmer and Lemeshow's goodness-of-fit χ(2)test. CA-125 velocity decreased as the number of CA-125 measurements increased but was unaffected by age at baseline screen and family history of ovarian cancer. The average velocity (19.749U/ml per month) of the cancer group was more than 500 times the average velocity (0.035U/ml per month) of the non-cancer group. Among six covariates used in the model, CA-125 velocity and time intervals between baseline and second to last screening test and between last two screening tests were statistically significant predictors of ovarian cancer. The chance of having ovarian cancer increased as velocity increased, and the chance decreased when the time intervals between baseline and the second to last screening test and between last two screening tests of an individual increased. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. Knockdown of Eag1 Expression by RNA Interference Increases Chemosensitivity to Cisplatin in Ovarian Cancer Cells.

    Science.gov (United States)

    Hui, Chen; Lan, Zhang; Yue-li, Lin; Li-lin, Hong; Li-lin, Huang

    2015-12-01

    Ether á go-go 1 (Eag1) is frequently highly expressed in various malignant cancers and its excessive expression is correlated with poor prognosis in various cancers. However, the relationship of Eag1 expression with the clinical outcome of patients having ovarian cancer treated with cisplatin-based adjuvant chemotherapy is still unknown. In this study, we measured the expression of Eag1 in ovarian cancer and investigated the association between cisplatin chemosensitivity of ovarian cancer cells and Eag1 expression level. We demonstrate that decreased expression of Eag1 correlates with favorable prognosis in patients treated with cisplatin-based adjuvant chemotherapy and predicts higher cisplatin sensitivity in ovarian cancer cells. In vitro, knockdown of Eag1 by small interfering RNA facilitated the sensitivity of ovarian cancer cells (SKOV3 and TYK) to cisplatin-induced apoptosis via nuclear factor κ-light chain-enhancer of activated B cells (NF-κB) pathway. Furthermore, knockdown of Eag1 expression was associated with decreased expression of the P-glycoprotein without affecting multidrug resistance-associated protein 1 expression. Taken together, Eag1 may serve as a potential indicator to predict Eag1 chemosensitivity, and silencing Eag1 may represent a potential therapeutic strategy for ovarian cancer. © The Author(s) 2015.

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

    OpenAIRE

    King, Melony G; Olson, Sara H; Paddock, Lisa; Chandran, Urmila; Demissie, Kitaw; Lu, Shou-En; Parekh, Niyati; Rodriguez-Rodriguez, Lorna; Bandera, Elisa V

    2013-01-01

    Background Ovarian cancer is the deadliest gynecologic cancer in the US. The consumption of refined sugars has increased dramatically over the past few decades, accounting for almost 15% of total energy intake. Yet, there is limited evidence on how sugar consumption affects ovarian cancer risk. Methods We evaluated ovarian cancer risk in relation to sugary foods and beverages, and total and added sugar intakes in a population-based case?control study. Cases were women with newly diagnosed epi...

  1. Absence of significant germ line p53 mutations in ovarian cancer patients.

    Science.gov (United States)

    Buller, R E; Skilling, J S; Kaliszewski, S; Niemann, T; Anderson, B

    1995-09-01

    Germ line mutations of the p53 gene have been described in the Li-Fraumeni Cancer Family Syndrome and occur in patients with multifocal gliomas, particularly those with a history of a metachronous cancer or a family history of cancer. p53 dysfunction is often associated with ovarian cancer. Patients with ovarian carcinoma frequently develop synchronous or metachronous cancers and may have a family history of this or related cancers. Thus, we hypothesized that germ line p53 mutations might be associated with a significant proportion of ovarian cancers. Germ line DNA isolated from peripheral leukocytes of 73 patients with ovarian carcinoma was screened for p53 sequence abnormalities utilizing single-strand conformation polymorphism analysis and direct PCR sequencing techniques. As many as 40% of this cohort of ovarian cancer patients from 67 families may represent familial phenotypes. Synchronous and metachronous cancers occurred in 19% of the cohort. Only two intron-based polymorphisms were found. Neither has been previously reported. One of these, in intron 6, occurred in three unrelated patients all of whom had a history of metachronous breast cancer. A polymorphism in intron 10 occurred in a patient with synchronous endometrial cancer. No classic germ line mutations of p53 were found.

  2. Human chorionic gonadotropin and its relation to grade, stage and patient survival in ovarian cancer

    International Nuclear Information System (INIS)

    Lenhard, Miriam; Tsvilina, Alexandra; Schumacher, Lan; Kupka, Markus; Ditsch, Nina; Mayr, Doris; Friese, Klaus; Jeschke, Udo

    2012-01-01

    An influence of gonadotropins (hCG) on the development of ovarian cancer has been discussed. Therefore, we quantified serum hCG levels in patients with benign and malignant ovarian tumors and the hCG expression in ovarian cancer tissue in order to analyze its relation to grade, stage, gonadotropin receptor (LH-R, FSH-R) expression and survival in ovarian cancer patients. Patients diagnosed and treated for ovarian tumors from 1990 to 2002 were included. Patient characteristics, histology including histological subtype, tumor stage, grading and follow-up data were available. Serum hCG concentration measurement was performed with ELISA technology, hCG tissue expression determined by immunohistochemistry. HCG-positive sera were found in 26.7% of patients with benign and 67% of patients with malignant ovarian tumors. In addition, significantly higher hCG serum concentrations were observed in patients with malignant compared to benign ovarian tumors (p = 0.000). Ovarian cancer tissue was positive for hCG expression in 68%. We identified significant differences in hCG tissue expression related to tumor grade (p = 0.022) but no differences with regard to the histological subtype. In addition, mucinous ovarian carcinomas showed a significantly increased hCG expression at FIGO stage III compared to stage I (p = 0.018). We also found a positive correlation of hCG expression to LH-R expression, but not to FSH-R expression. There was no significant correlation between tissue hCG expression and overall ovarian cancer patient survival, but subgroup analysis revealed an increased 5-year survival in LH-R positive/FSH-R negative and hCG positive tumors (hCG positive 75.0% vs. hCG negative 50.5%). Serum human gonadotropin levels differ in patients with benign and malignant ovarian tumors. HCG is often expressed in ovarian cancer tissue with a certain variable relation to grade and stage. HCG expression correlates with LH-R expression in ovarian cancer tissue, which has previously

  3. Human chorionic gonadotropin and its relation to grade, stage and patient survival in ovarian cancer

    Science.gov (United States)

    2012-01-01

    Background An influence of gonadotropins (hCG) on the development of ovarian cancer has been discussed. Therefore, we quantified serum hCG levels in patients with benign and malignant ovarian tumors and the hCG expression in ovarian cancer tissue in order to analyze its relation to grade, stage, gonadotropin receptor (LH-R, FSH-R) expression and survival in ovarian cancer patients. Methods Patients diagnosed and treated for ovarian tumors from 1990 to 2002 were included. Patient characteristics, histology including histological subtype, tumor stage, grading and follow-up data were available. Serum hCG concentration measurement was performed with ELISA technology, hCG tissue expression determined by immunohistochemistry. Results HCG-positive sera were found in 26.7% of patients with benign and 67% of patients with malignant ovarian tumors. In addition, significantly higher hCG serum concentrations were observed in patients with malignant compared to benign ovarian tumors (p = 0.000). Ovarian cancer tissue was positive for hCG expression in 68%. We identified significant differences in hCG tissue expression related to tumor grade (p = 0.022) but no differences with regard to the histological subtype. In addition, mucinous ovarian carcinomas showed a significantly increased hCG expression at FIGO stage III compared to stage I (p = 0.018). We also found a positive correlation of hCG expression to LH-R expression, but not to FSH-R expression. There was no significant correlation between tissue hCG expression and overall ovarian cancer patient survival, but subgroup analysis revealed an increased 5-year survival in LH-R positive/FSH-R negative and hCG positive tumors (hCG positive 75.0% vs. hCG negative 50.5%). Conclusions Serum human gonadotropin levels differ in patients with benign and malignant ovarian tumors. HCG is often expressed in ovarian cancer tissue with a certain variable relation to grade and stage. HCG expression correlates with LH-R expression in ovarian

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

    NARCIS (Netherlands)

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

    2012-01-01

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

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

    NARCIS (Netherlands)

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

    2012-01-01

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

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

    NARCIS (Netherlands)

    Ding, Y.C.; McGuffog, L.; Healey, S.; Friedman, E.; Laitman, Y.; Paluch-Shimon, S.; Kaufman, B.; Liljegren, A.; Lindblom, A.; Olsson, H.; Kristoffersson, U.; Stenmark-Askmalm, M.; Melin, B.; Domchek, S.M.; Nathanson, K.L.; Rebbeck, T.R.; Jakubowska, A.; Lubinski, J.; Jaworska, K.; Durda, K.; Gronwald, J.; Huzarski, T.; Cybulski, C.; Byrski, T.; Osorio, A.; Cajal, T.R.; Stavropoulou, A.V.; Benitez, J.; Hamann, U.; Rookus, M.; Aalfs, C.M.; Lange, J.L. de; Meijers-Heijboer, H.E.; Oosterwijk, J.C.; Asperen, C.J. van; Gomez Garcia, E.B.; Hoogerbrugge, N.; Jager, A.; Luijt, R.B. van der; Easton, D.F.; Peock, S.; Frost, D.; Ellis, S.D.; Platte, R.; Fineberg, E.; Evans, D.G.; Lalloo, F.; Izatt, L.; Eeles, R.; Adlard, J.; Davidson, R.; Eccles, D.; Cole, T.; Cook, J.; Brewer, C.; Tischkowitz, M.; Godwin, A.K.; Pathak, H.; Stoppa-Lyonnet, D.; Sinilnikova, O.M.; Mazoyer, S.; Barjhoux, L.; Leone, M.; Gauthier-Villars, M.; Caux-Moncoutier, V.; Pauw, A. de; Hardouin, A.; Berthet, P.; Dreyfus, H.; Ferrer, S.F.; Collonge-Rame, M.A.; Sokolowska, J.; Buys, S.; Daly, M.; Miron, A.; Terry, M.B.; Chung, W.; John, E.M.; Southey, M.; Goldgar, D.; Singer, C.F.; Tea, M.K.; Gschwantler-Kaulich, D.; Fink-Retter, A.; Hansen, T.V.; Ejlertsen, B.; Johannsson, O.T.; Offit, K.; Sarrel, K.; Gaudet, M.M.; Vijai, J.; Robson, M.; Piedmonte, M.R.; Andrews, L.; Cohn, D.; Demars, L.R.; Disilvestro, P.; Rodriguez, G.; Toland, A.E.; Montagna, M.; Agata, S.; Imyanitov, E.; Isaacs, C.; Janavicius, R.; Lazaro, C.; Blanco, I.; Ramus, S.J.; Sucheston, L.; Karlan, B.Y.; Gross, J.; Ganz, P.A.; Beattie, M.S.; Schmutzler, R.K.; Wappenschmidt, B.; Meindl, A.; Arnold, N.; Niederacher, D.; Preisler-Adams, S.; Gadzicki, D.; Varon-Mateeva, R.; Deissler, H.; Gehrig, A.; Sutter, C.; Kast, K.; Nevanlinna, H.; Aittomaki, K.; Simard, J.; Spurdle, A.B.; Beesley, J.; Chen, X.; Tomlinson, G.E.; Weitzel, J.; Garber, J.E.; Olopade, O.I.; Rubinstein, W.S.; Tung, N.; Blum, J.L.; Narod, S.A.; Brummel, S.; Gillen, D.L.; Lindor, N.; Fredericksen, Z.; Pankratz, V.S.; Couch, F.J.; Radice, P.; Peterlongo, P.; Greene, M.H.; Loud, J.T.; Mai, P.L.; Andrulis, I.L.; Glendon, G.; Ozcelik, H.; Gerdes, A.M.; Thomassen, M.; Jensen, U.B.; Skytte, A.B.; Caligo, M.A.; Lee, A.; Chenevix-Trench, G.; Antoniou, A.C.; Neuhausen, S.L.

    2012-01-01

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

  7. Expression and function of androgen receptor coactivator p44/Mep50/WDR77 in ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Martin Ligr

    Full Text Available Hormones, including estrogen and progesterone, and their receptors play an important role in the development and progression of ovarian carcinoma. Androgen, its receptor and coactivators have also been implicated in these processes. p44/Mep50/WDR77 was identified as a subunit of the methylosome complex and lately characterized as a steroid receptor coactivator that enhances androgen receptor as well as estrogen receptor-mediated transcriptional activity in a ligand-dependent manner. We previously described distinct expression and function of p44 in prostate, testis, and breast cancers. In this report, we examined the expression and function of p44 in ovarian cancer. In contrast to findings in prostate and testicular cancer and similar to breast cancer, p44 shows strong cytoplasmic localization in morphologically normal ovarian surface and fallopian tube epithelia, while nuclear p44 is observed in invasive ovarian carcinoma. We observed that p44 can serve as a coactivator of both androgen receptor (AR and estrogen receptor (ER in ovarian cells. Further, overexpression of nuclear-localized p44 stimulates proliferation and invasion in ovarian cancer cells in the presence of estrogen or androgen. These findings strongly suggest that p44 plays a role in mediating the effects of hormones during ovarian tumorigenesis.

  8. Comprehensive Quantitative Analysis of Ovarian and Breast Cancer Tumor Peptidomes

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Zhe; Wu, Chaochao; Xie, Fang; Slysz, Gordon W.; Tolic, Nikola; Monroe, Matthew E.; Petyuk, Vladislav A.; Payne, Samuel H.; Fujimoto, Grant M.; Moore, Ronald J.; Fillmore, Thomas L.; Schepmoes, Athena A.; Levine, Douglas; Townsend, Reid; Davies, Sherri; Li, Shunqiang; Ellis, Matthew; Boja, Emily; Rivers, Robert; Rodriguez, Henry; Rodland, Karin D.; Liu, Tao; Smith, Richard D.

    2015-01-02

    Aberrant degradation of proteins is associated with many pathological states, including cancers. Mass spectrometric analysis of tumor peptidomes, the intracellular and intercellular products of protein degradation, has the potential to provide biological insights on proteolytic processing in cancer. However, attempts to use the information on these smaller protein degradation products from tumors for biomarker discovery and cancer biology studies have been fairly limited to date, largely due to the lack of effective approaches for robust peptidomics identification and quantification, and the prevalence of confounding factors and biases associated with sample handling and processing. Herein, we have developed an effective and robust analytical platform for comprehensive analyses of tissue peptidomes, which is suitable for high throughput quantitative studies. The reproducibility and coverage of the platform, as well as the suitability of clinical ovarian tumor and patient-derived breast tumor xenograft samples with post-excision delay of up to 60 min before freezing for peptidomics analysis, have been demonstrated. Moreover, our data also show that the peptidomics profiles can effectively separate breast cancer subtypes, reflecting tumor-associated protease activities. Peptidomics complements results obtainable from conventional bottom-up proteomics, and provides insights not readily obtainable from such approaches.

  9. Family History of Breast Cancer as a Determinant of the Risk of Developing Endometrial and Ovarian Cancers: A Nationwide Cohort Study

    Science.gov (United States)

    2002-01-01

    Prophylactic surgery in women with a hereditary predisposition to breast and ovarian cancer . J Clin Oncol 2000;18:1980-95. Eerola H, Blomqvist C...to represent clinical clues to the presence of a hereditary cancer predisposition . C) Genetic studies: The hereditary breast /ovarian cancer ...harbingers of a genetic predisposition to breast cancer , we analyzed the risk of endometrial cancer taking this

  10. Novel paradigm for immunotherapy of ovarian cancer by engaging prophylactic immunity against hepatitis B virus.

    Science.gov (United States)

    Malecki, Marek; Putzer, Emily; Quach, Caroline; Dodivenaka, Chaitanya; Tombokan, Xenia

    2016-12-01

    Only eight women out of one hundred diagnosed with ovarian epithelial cancers, which progressed to the clinical stage IV, survive 10 years. First line therapies: surgery, chemotherapy, and radiation therapy inflict very serious iatrogenic consequences. Passive immunotherapy of ovarian cancers offers only low efficacy. Prophylactic and therapeutic vaccines for ovarian cancers are not available. Interestingly, prophylactic vaccines for Hepatitis B Viruses (HBV) are very effective. The specific aim of this work was to design, synthesize, and administer biomolecules, which would engage prophylactic, vaccination-induced immunity for HBV towards killing of ovarian cancer cells with high specificity and efficacy. Tissue biopsies, ascites, and blood were acquired from the patients, whose identities were entirely concealed in accordance with the Declaration of Helsinki, pursuant to the Institutional Review Board approval, and with the Patients' informed consent. By biomolecular engineering, we have created a novel family of biomolecules: antibody × vaccine engineered constructs (AVEC: anti-HER-2 × HBsAg). We have collected the blood from the volunteers, and measured the titers of anti-HBV antibodies resulting from the FDA approved and CDC scheduled HBV vaccinations. We have acquired tumor biopsies, ascites, and blood from patients suffering from the advanced ovarian cancers. We have established cultures of HER-2 over-expressing epithelial ovarian cancers: OV-90, TOC-112D, SKOV-3, as well as human ovary surface epithelial (HOSE) and human artery endothelial (HAE) cells. Treatment of the HER-2+ ovarian cancer cells with AVEC: anti-HER-2 × HBsAg, accompanied by administration of blood drawn from patients with high titers of the anti-HBV antibodies, resulted in much higher therapeutic efficacy as compared to treatment with the naked anti-HER-2 antibodies alone and/or with the relevant isotype antibodies. This treatment had practically no effect upon the HOSE and HAE

  11. Targeting ILK and β4 integrin abrogates the invasive potential of ovarian cancer

    International Nuclear Information System (INIS)

    Choi, Yoon Pyo; Kim, Baek Gil; Gao, Ming-Qing; Kang, Suki; Cho, Nam Hoon

    2012-01-01

    Highlights: ► The potential of targeting ILK and integrins for highly aggressive ovarian cancer. ► Unanticipated synergistic effect for the combination of ILK/β4 integrin. ► Combination of ILK/β4 integrin effectively inhibited the PI3K/Akt/Rac1 cascade. ► Targeting of β4 integrin/ILK had potent inhibitory effects in ovarian cancer. -- Abstract: Integrins and integrin-linked kinase (ILK) are essential to cancerous invasion because they mediate physical interactions with the extracellular matrix, and regulate oncogenic signaling pathways. The purpose of our study is to determine whether deletion of β1 and β4 integrin and ILK, alone or in combination, has antitumoral effects in ovarian cancer. Expression of β1 and β4 integrin and ILK was analyzed by immunohistochemistry in 196 ovarian cancer tissue samples. We assessed the effects of depleting these molecules with shRNAs in ovarian cancer cells by Western blot, conventional RT-PCR, cell proliferation, migration, invasion, and in vitro Rac1 activity assays, and in vivo xenograft formation assays. Overexpression of β4 integrin and ILK in human ovarian cancer specimens was found to correlate with tumor aggressiveness. Depletion of these targets efficiently suppresses ovarian cancer cell proliferation, migration, and invasion in vitro and xenograft tumor formation in vivo. We also demonstrated that single depletion of ILK or combination depletion of β4 integrin/ILK inhibits phosphorylation of downstream signaling targets, p-Ser 473 Akt and p-Thr202/Tyr204 Erk1/2, and activation of Rac1, as well as reduce expression of MMP-2 and MMP-9 and increase expression of caspase-3 in vitro. In conclusion, targeting β4 integrin combined with ILK can instigate the latent tumorigenic potential and abrogate the invasive potential in ovarian cancer.

  12. Targeting ILK and {beta}4 integrin abrogates the invasive potential of ovarian cancer

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Yoon Pyo; Kim, Baek Gil [BK21 Project for Medical Science, Yonsei University College of Medicine, Seoul (Korea, Republic of); Department of Pathology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Gao, Ming-Qing; Kang, Suki [Department of Pathology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Cho, Nam Hoon, E-mail: cho1988@yuhs.ac [BK21 Project for Medical Science, Yonsei University College of Medicine, Seoul (Korea, Republic of); Department of Pathology, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2012-10-26

    Highlights: Black-Right-Pointing-Pointer The potential of targeting ILK and integrins for highly aggressive ovarian cancer. Black-Right-Pointing-Pointer Unanticipated synergistic effect for the combination of ILK/{beta}4 integrin. Black-Right-Pointing-Pointer Combination of ILK/{beta}4 integrin effectively inhibited the PI3K/Akt/Rac1 cascade. Black-Right-Pointing-Pointer Targeting of {beta}4 integrin/ILK had potent inhibitory effects in ovarian cancer. -- Abstract: Integrins and integrin-linked kinase (ILK) are essential to cancerous invasion because they mediate physical interactions with the extracellular matrix, and regulate oncogenic signaling pathways. The purpose of our study is to determine whether deletion of {beta}1 and {beta}4 integrin and ILK, alone or in combination, has antitumoral effects in ovarian cancer. Expression of {beta}1 and {beta}4 integrin and ILK was analyzed by immunohistochemistry in 196 ovarian cancer tissue samples. We assessed the effects of depleting these molecules with shRNAs in ovarian cancer cells by Western blot, conventional RT-PCR, cell proliferation, migration, invasion, and in vitro Rac1 activity assays, and in vivo xenograft formation assays. Overexpression of {beta}4 integrin and ILK in human ovarian cancer specimens was found to correlate with tumor aggressiveness. Depletion of these targets efficiently suppresses ovarian cancer cell proliferation, migration, and invasion in vitro and xenograft tumor formation in vivo. We also demonstrated that single depletion of ILK or combination depletion of {beta}4 integrin/ILK inhibits phosphorylation of downstream signaling targets, p-Ser 473 Akt and p-Thr202/Tyr204 Erk1/2, and activation of Rac1, as well as reduce expression of MMP-2 and MMP-9 and increase expression of caspase-3 in vitro. In conclusion, targeting {beta}4 integrin combined with ILK can instigate the latent tumorigenic potential and abrogate the invasive potential in ovarian cancer.

  13. Delivering widespread BRCA testing and PARP inhibition to patients with ovarian cancer.

    Science.gov (United States)

    George, Angela; Kaye, Stan; Banerjee, Susana

    2017-05-01

    The treatment of patients with ovarian cancer is rapidly changing following the success of poly [ADP-ribose] polymerase (PARP) inhibitors in clinical trials. Olaparib is the first PARP inhibitor to be approved by the EMA and FDA for BRCA-mutated ovarian cancer. Germ line BRCA mutation status is now established as a predictive biomarker of potential benefit from treatment with a PARP inhibitor; therefore, knowledge of the BRCA status of an individual patient with ovarian cancer is essential, in order to guide treatment decisions. BRCA testing was previously offered only to women with a family or personal history of breast and/or ovarian cancer; however, almost 20% of women with high-grade serous ovarian cancer are now recognized to harbour a germ line BRCA mutation, and of these, >40% might not have a family history of cancer and would not have received BRCA testing. A strategy to enable more widespread implementation of BRCA testing in routine care is, therefore, necessary. In this Review, we summarize data from key clinical trials of PARP inhibitors and discuss how to integrate these agents into the current treatment landscape of ovarian cancer. The validity of germ line BRCA testing and other promising biomarkers of homologous-recombination deficiency will also be discussed.

  14. Molecular epigenetics in the management of ovarian cancer: Are we investigating a rational clinical promise?

    Directory of Open Access Journals (Sweden)

    Ha eNguyen

    2014-04-01

    Full Text Available Epigenetics is essentially a phenotypical change in gene expression without any alteration of the DNA sequence; the emergence of epigenetics in cancer research and mainstream oncology is fueling new hope. However, it is not yet known whether this knowledge will translate to improved clinical management of ovarian cancer. In this malignancy, women are still undergoing chemotherapy similar to what was approved in 1978, which to this day represents one of the biggest breakthroughs for treating ovarian cancer. While liquid tumors are benefitting from epigenetically-related therapies, solid tumors like ovarian cancer are not (yet?. Herein we will review the science of molecular epigenetics, especially DNA methylation, histone modifications and microRNA, but also include transcription factors since they, too, are important in ovarian cancer. Preclinical and clinical research on the role of epigenetic modifications is summarized as well. Sadly, ovarian cancer remains an idiopathic disease, for the most part, and there are many areas of patient management which could benefit from improved technology. This review will also highlight the evidence suggesting that epigenetics may have preclinical utility in pharmacology and clinical applications for prognosis and diagnosis. Lastly, drugs currently in clinical trials (i.e. histone deacetylase inhibitors are discussed along with the promise for epigenetics in the exploitation of chemoresistance. Whether epigenetics will ultimately be the answer to better management in ovarian cancer is currently unknown; what we have now is hope.

  15. [Expressions of Ras and Sos1 in epithelial ovarian cancer tissues and their clinical significance].

    Science.gov (United States)

    Xiao, Zheng-Hua; Linghu, Hua; Liu, Qian-Fen

    2016-11-20

    To detect the expressions of Ras and Sos1 proteins in human epithelial ovarian cancer (EOC) tissues and explore their correlation with the clinicopathological features of the patients. The expressions of Ras and Sos1 proteins were detected immunohistochemically in 62 EOC tissues, 5 borderline ovarian cancer tissues, 15 benign epithelial ovarian neoplasm tissues, and 18 normal ovarian tissues. The EOC tissues showed significantly higher expression levels of both Ras and Sos1 than the other tissues tested (Ptissues, Ras and Sos1 proteins were expressed mostly on the cell membrane and in the cytoplasm. The expression level of Ras was correlated with pathological types of the tumor (Ptissue-specific variation of Ras expression can lend support to a specific diagnosis of ovarian serous adenocarcinoma. The association of Ras and Sos1 protein expression with the tumor-free survival time of the patients awaits further investigation with a larger sample size.

  16. Birth weight and the risk of histological subtypes of ovarian and endometrial cancers

    DEFF Research Database (Denmark)

    Trabert, Britton; Aarestrup, Julie; Ulrich, Lian G

    2018-01-01

    BACKGROUND: Studies of birth weight associations with ovarian and endometrial cancer risks are limited with inconsistent results, and none has evaluated associations by histologic subtype. We utilized prospectively collected birth weight information to investigate the association with risk of ova...

  17. Association between endometriosis and risk of histological subtypes of ovarian cancer

    DEFF Research Database (Denmark)

    Pearce, Celeste Leigh; Templeman, Claire; Rossing, Mary Anne

    2012-01-01

    Endometriosis is a risk factor for epithelial ovarian cancer; however, whether this risk extends to all invasive histological subtypes or borderline tumours is not clear. We undertook an international collaborative study to assess the association between endometriosis and histological subtypes...

  18. Multidisciplinary Strategies in the Prevention and Early Detection of Ovarian Cancer

    National Research Council Canada - National Science Library

    Mok, Samuel

    2003-01-01

    .... They have shown that Protease M over-expressed in a majority of stage I tumors and can be secreted by ovarian cancer cells in Project 2, suggesting that it is a potential marker for early detection of the disease...

  19. Multidisciplinary Strategies in the Prevention and Early Detection of Ovarian Cancer

    National Research Council Canada - National Science Library

    Mok, Samuel

    2001-01-01

    This program project consists of 4 research projects. Project I studies genetic changes in microdissected microscopic Stage I ovarian cancer cells, and identify markers for early detection of the disease...

  20. Targeting Angiogenic Factors Contributing to Etiology and Progression of Human Ovarian Cancer

    National Research Council Canada - National Science Library

    Pietras, Richard

    2002-01-01

    .... Herceptin, an antibody to HER-2 receptor, has direct antitumor effects, but the antireceptor antibody also elicits a significant reduction in VEGF secretion from ovarian cancer cells,and, thereby...