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Sample records for active ovarian cancer

  1. Ovarian Cancer

    Science.gov (United States)

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

  2. Antigen-specific active immunotherapy for ovarian cancer

    NARCIS (Netherlands)

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

    2010-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Andrew E Teschendorff

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

  4. Ovarian Cancer

    Science.gov (United States)

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

  5. How Is Ovarian Cancer Diagnosed?

    Science.gov (United States)

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

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

    Science.gov (United States)

    2014-10-01

    cells and host cells during ovarian cancer progression. We will use an innovative strategy to define patterns of NF-κB activity in ovarian cancer...placed to study the role of NF-κB signaling in ovarian cancer using highly innovative syngeneic models, allowing its role in both tumor and host cells...epithelium promotes milk loss during mammary development and infection. Journal of Cellular Physiology 222:73-81, 2010. PMCID: PMC2783968. 3. Connelly L

  7. How Is Ovarian Cancer Staged?

    Science.gov (United States)

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

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

    NARCIS (Netherlands)

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

    2008-01-01

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

  9. 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

  10. National Ovarian Cancer Coalition

    Science.gov (United States)

    ... List Signs & Symptoms Potential signs and symptoms of ovarian cancer: Bloating Pelvic or abdominal pain Trouble eating or ... to urinate urgently or often Other symptoms of ovarian cancer can include: Fatigue Upset stomach or heartburn Back ...

  11. Screening for Ovarian Cancer

    Science.gov (United States)

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

  12. 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....

  13. Ovarian Autoantibodies Predict Ovarian Cancer

    Science.gov (United States)

    2010-11-01

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

  14. Symptoms of Ovarian Cancer

    Science.gov (United States)

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

  15. Can Ovarian Cancer Be Prevented?

    Science.gov (United States)

    ... Ovarian Cancer Causes, Risk Factors, and Prevention Can Ovarian Cancer Be Prevented? Most women have one or more ... strategies for women with a family history of ovarian cancer or BRCA mutation If your family history suggests ...

  16. Physical activity and risk of ovarian cancer: Results from the Netherlands Cohort Study (The Netherlands)

    NARCIS (Netherlands)

    Biesma, R.G.; Schouten, L.J.; Dirx, M.J.M.; Goldbohm, R.A.; Brandt, P.A. van den

    2006-01-01

    Objective: To investigate the association between nonoccupational physical activity and the risk of ovarian cancer among post-menopausal women. Methods: The Netherlands Cohort Study on Diet and Cancer consists of 62,573 women aged 55-69 years at baseline. Information regarding baseline nonoccupation

  17. Ovarian Cancer FAQ

    Science.gov (United States)

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

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

    Directory of Open Access Journals (Sweden)

    Tiffany J Tzeng

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

  19. The influence of theobromine on angiogenic activity and proangiogenic cytokines production of human ovarian cancer cells.

    Science.gov (United States)

    Barcz, E; Sommer, E; Sokolnicka, I; Gawrychowski, K; Roszkowska-Purska, K; Janik, P; Skopinska-Rózewska, E

    1998-01-01

    Angiogenesis plays an important role in ovarian cancer growth and metastasis formation. Adenosine is one of the most potent stimulator of neovascularisation. The aim of present study was to determine if theobromine, adenosine receptor antagonist, influences angiogenic activity and proangiogenic cytokines production. Theobromine caused significant inhibition of angiogenic activity of ovarian cancer cells. In in vivo and in vitro cultures theobromine diminished vascular endothelial growth factor (VEGF) production. Production of basic fibroblast growth factor (bFGF) and interleukin-8 (IL-8) was not altered by the examined drug. These findings suggest that theobromine might be a potent inhibitor of angiogenesis induced by ovarian cancer cells and its mechanism of action is related to inhibition of VEGF production.

  20. Ovarian Cancer Stage II

    Science.gov (United States)

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

  1. Ovarian Cancer Stage IIIC

    Science.gov (United States)

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

  2. Ovarian Cancer Stage I

    Science.gov (United States)

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

  3. Ovarian Cancer Stage IV

    Science.gov (United States)

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

  4. Can Ovarian Cancer Be Found Early?

    Science.gov (United States)

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

  5. What Are the Key Statistics about Ovarian Cancer?

    Science.gov (United States)

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

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

    Science.gov (United States)

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

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

    Science.gov (United States)

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

    2007-11-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  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. Estrogen biosynthesis and action in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Theresia eThalhammer

    2014-11-01

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

  11. [Oxaliplatin and ovarian cancer].

    Science.gov (United States)

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

    2006-02-01

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

  12. Regulation of gene expression in ovarian cancer cells by luteinizing hormone receptor expression and activation

    Directory of Open Access Journals (Sweden)

    Dam Phuongan

    2011-06-01

    Full Text Available Abstract Background Since a substantial percentage of ovarian cancers express gonadotropin receptors and are responsive to the relatively high concentrations of pituitary gonadotropins during the postmenopausal years, it has been suggested that receptor activation may contribute to the etiology and/or progression of the neoplasm. The goal of the present study was to develop a cell model to determine the impact of luteinizing hormone (LH receptor (LHR expression and LH-mediated LHR activation on gene expression and thus obtain insights into the mechanism of gonadotropin action on ovarian surface epithelial (OSE carcinoma cells. Methods The human ovarian cancer cell line, SKOV-3, was stably transfected to express functional LHR and incubated with LH for various periods of time (0-20 hours. Transcriptomic profiling was performed on these cells to identify LHR expression/activation-dependent changes in gene expression levels and pathways by microarray and qRT-PCR analyses. Results Through comparative analysis on the LHR-transfected SKOV-3 cells exposed to LH, we observed the differential expression of 1,783 genes in response to LH treatment, among which five significant families were enriched, including those of growth factors, translation regulators, transporters, G-protein coupled receptors, and ligand-dependent nuclear receptors. The most highly induced early and intermediate responses were found to occupy a network impacting transcriptional regulation, cell growth, apoptosis, and multiple signaling transductions, giving indications of LH-induced apoptosis and cell growth inhibition through the significant changes in, for example, tumor necrosis factor, Jun and many others, supportive of the observed cell growth reduction in in vitro assays. However, other observations, e.g. the substantial up-regulation of the genes encoding the endothelin-1 subtype A receptor, stromal cell-derived factor 1, and insulin-like growth factor II, all of which are

  13. Managing hereditary ovarian cancer

    NARCIS (Netherlands)

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

    2009-01-01

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

  14. TP53 and ovarian cancer

    NARCIS (Netherlands)

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

    2003-01-01

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

  15. What Will Happen After Treatment for Ovarian Cancer?

    Science.gov (United States)

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

  16. The Interaction of Adrenomedullin and Macrophages Induces Ovarian Cancer Cell Migration via Activation of RhoA Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Xiaoyan Pang

    2013-01-01

    Full Text Available Tumor-associated macrophages (TAMs are correlated with poor prognosis in many human cancers; however, the mechanism by which TAMs facilitate ovarian cancer cell migration and invasion remains unknown. This study was aimed to examine the function of adrenomedullin (ADM in macrophage polarization and their further effects on the migration of ovarian cancer cells. Exogenous ADM antagonist and small interfering RNA (siRNA specific for ADM expression were treated to macrophages and EOC cell line HO8910, respectively. Then macrophages were cocultured with HO8910 cells without direct contact. Flow cytometry, Western blot and real-time PCR were used to detect macrophage phenotype and cytokine production. The migration ability and cytoskeleton rearrangement of ovarian cancer cells were determined by Transwell migration assay and phalloidin staining. Western blot was performed to evaluate the activity status of signaling molecules in the process of ovarian cancer cell migration. The results showed that ADM induced macrophage phenotype and cytokine production similar to TAMs. Macrophages polarized by ADM promoted the migration and cytoskeleton rearrangement of HO8910 cells. The expression of RhoA and its downstream effector, cofilin, were upregulated in macrophage-induced migration of HO8910 cells. In conclusion, ADM could polarize macrophages similar to TAMs, and then polarized macrophages promote the migration of ovarian cancer cells via activation of RhoA signaling pathway in vitro.

  17. MiR-1207 overexpression promotes cancer stem cell-like traits in ovarian cancer by activating the Wnt/β-catenin signaling pathway.

    Science.gov (United States)

    Wu, Geyan; Liu, Aibin; Zhu, Jinrong; Lei, Fangyong; Wu, Shu; Zhang, Xin; Ye, Liping; Cao, Lixue; He, Shanyang

    2015-10-06

    Wnt/β-catenin signaling pathway is strictly controlled by multiple negative regulators. However, how tumor cells override the negative regulatory effects to maintain constitutive activation of Wnt/β-catenin signaling, which is commonly observed in various cancers, remains puzzling. In current study, we reported that overexpression of miR-1207 in ovarian cancer activated Wnt/β-catenin signaling by directly targeting and suppressing secreted Frizzled-related protein 1 (SFRP1), AXIN2 and inhibitor of β-catenin and TCF-4 (ICAT), which are vital negative regulators of the Wnt/β-catenin pathway. We found that the expression of miR-1207 was ubiquitously upregulated in both ovarian cancer tissues and cells, which inversely correlated with patient overall survival. Furthermore, overexpression of miR-1207 enhanced, while silencing miR-1207 reduced, stem cell-like traits of ovarian cancer cells in vitro and in vivo, including tumor sphere formation capability and proportion of SP+ and CD133+ cells. Importantly, upregulating miR-1207 promoted, while silencing miR-1207 inhibited, the tumorigenicity of ovarian cancer cells. Hence, our results suggest that miR-1207 plays a vital role in promoting the cancer stem cell-like phenotype in ovarian cancer and might represent a potential target for anti-ovarian cancer therapy.

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

    Science.gov (United States)

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

    2016-07-01

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

  19. Hormone therapy and ovarian cancer

    DEFF Research Database (Denmark)

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

    2009-01-01

    CONTEXT: Studies have suggested an increased risk of ovarian cancer among women taking postmenopausal hormone therapy. Data are sparse on the differential effects of formulations, regimens, and routes of administration. OBJECTIVE: To assess risk of ovarian cancer in perimenopausal...... of Medicinal Product Statistics provided individually updated exposure information. The National Cancer Register and Pathology Register provided ovarian cancer incidence data. Information on confounding factors and effect modifiers was from other national registers. Poisson regression analyses with 5-year age...... bands included hormone exposures as time-dependent covariates. PARTICIPANTS: A total of 909,946 women without hormone-sensitive cancer or bilateral oophorectomy. MAIN OUTCOME MEASURE: Ovarian cancer. RESULTS: In an average of 8.0 years of follow-up (7.3 million women-years), 3068 incident ovarian...

  20. Antiangiogenic therapies in ovarian cancer

    OpenAIRE

    Reinthaller, Alexander

    2016-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  2. Imunotherapy opportunities in ovarian cancer

    Directory of Open Access Journals (Sweden)

    I. Zh. Shubina

    2013-01-01

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

  3. AKT activation drives the nuclear localization of CSE1L and a pro-oncogenic transcriptional activation in ovarian cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Lorenzato, Annalisa; Biolatti, Marta [Department of Oncology, University of Torino School of Medicine, Torino (Italy); Institute for Cancer Research at Candiolo, Candiolo, Torino (Italy); Delogu, Giuseppe [Department of Biomedical Sciences-Histology, University of Sassari, Sassari (Italy); Capobianco, Giampiero [Department of Surgical, Microsurgical and Medical Sciences, University of Sassari, Sassari (Italy); Farace, Cristiano [Department of Biomedical Sciences-Histology, University of Sassari, Sassari (Italy); Dessole, Salvatore; Cossu, Antonio; Tanda, Francesco [Department of Surgical, Microsurgical and Medical Sciences, University of Sassari, Sassari (Italy); Madeddu, Roberto [Department of Biomedical Sciences-Histology, University of Sassari, Sassari (Italy); National Institute of Biostructures and Biosystems, Rome (Italy); Olivero, Martina [Department of Oncology, University of Torino School of Medicine, Torino (Italy); Institute for Cancer Research at Candiolo, Candiolo, Torino (Italy); Di Renzo, Maria Flavia, E-mail: mariaflavia.direnzo@unito.it [Department of Oncology, University of Torino School of Medicine, Torino (Italy); Institute for Cancer Research at Candiolo, Candiolo, Torino (Italy)

    2013-10-15

    The human homolog of the yeast cse1 gene (CSE1L) is over-expressed in ovarian cancer. CSE1L forms complex with Ran and importin-α and has roles in nucleocytoplasmic traffic and gene expression. CSE1L accumulated in the nucleus of ovarian cancer cell lines, while it was localized also in the cytoplasm of other cancer cell lines. Nuclear localization depended on AKT, which was constitutively active in ovarian cancer cells, as the CSE1L protein translocated to the cytoplasm when AKT was inactivated. Moreover, the expression of a constitutively active AKT forced the translocation of CSE1L from the cytoplasm to the nucleus in other cancer cells. Nuclear accrual of CSE1L was associated to the nuclear accumulation of the phosphorylated Ran Binding protein 3 (RanBP3), which depended on AKT as well. Also in samples of human ovarian cancer, AKT activation was associated to nuclear accumulation of CSE1L and phosphorylation of RanBP3. Expression profiling of ovarian cancer cells after CSE1L silencing showed that CSE1L was required for the expression of genes promoting invasion and metastasis. In agreement, CSE1L silencing impaired motility and invasiveness of ovarian cancer cells. Altogether these data show that in ovarian cancer cells activated AKT by affecting RanBP3 phosphorylation determines the nuclear accumulation of CSE1L and likely the nuclear concentration of transcription factors conveying pro-oncogenic signals. - highlights: • CSE1L is a key player in nucleocytoplasmic traffic by forming complex with Ran. • AKT phosphorylates RanBP3 that regulates the nucleocytoplasmic gradient of Ran. • The activated oncogenic AKT drives the nuclear accumulation of CSE1L. • CSE1L in the nucleus up-regulates genes conveying pro-oncogenic signals. • CSE1L might contribute to tumor progression driven by the activated oncogenic AKT.

  4. CA125 in ovarian cancer

    DEFF Research Database (Denmark)

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

    2005-01-01

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

  5. Subtypes of Ovarian Cancer and Ovarian Cancer Screening

    Science.gov (United States)

    Koshiyama, Masafumi; Matsumura, Noriomi; Konishi, Ikuo

    2017-01-01

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

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

    Science.gov (United States)

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

  7. Emerging treatments for ovarian cancer.

    Science.gov (United States)

    Muggia, Franco; Lu, M Janice

    2003-05-01

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

  8. Stathmin regulates mutant p53 stability and transcriptional activity in ovarian cancer.

    Science.gov (United States)

    Sonego, Maura; Schiappacassi, Monica; Lovisa, Sara; Dall'Acqua, Alessandra; Bagnoli, Marina; Lovat, Francesca; Libra, Massimo; D'Andrea, Sara; Canzonieri, Vincenzo; Militello, Loredana; Napoli, Marco; Giorda, Giorgio; Pivetta, Barbara; Mezzanzanica, Delia; Barbareschi, Mattia; Valeri, Barbara; Canevari, Silvana; Colombatti, Alfonso; Belletti, Barbara; Del Sal, Giannino; Baldassarre, Gustavo

    2013-05-01

    Stathmin is a p53-target gene, frequently overexpressed in late stages of human cancer progression. Type II High Grade Epithelial Ovarian Carcinomas (HG-EOC) represents the only clear exception to this observation. Here, we show that stathmin expression is necessary for the survival of HG-EOC cells carrying a p53 mutant (p53(MUT) ) gene. At molecular level, stathmin favours the binding and the phosphorylation of p53(MUT) by DNA-PKCS , eventually modulating p53(MUT) stability and transcriptional activity. Inhibition of stathmin or DNA-PKCS impaired p53(MUT) -dependent transcription of several M phase regulators, resulting in M phase failure and EOC cell death, both in vitro and in vivo. In primary human EOC a strong correlation exists between stathmin, DNA-PKCS , p53(MUT) overexpression and its transcriptional targets, further strengthening the relevance of the new pathway here described. Overall our data support the hypothesis that the expression of stathmin and p53 could be useful for the identification of high risk patients that will benefit from a therapy specifically acting on mitotic cancer cells.

  9. Tumor infiltrating lymphocytes in ovarian cancer.

    Science.gov (United States)

    Santoiemma, Phillip P; Powell, Daniel J

    2015-01-01

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

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

    Science.gov (United States)

    2017-02-19

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

  11. 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....

  12. Anticancer activity of liposomal cisplatin in preclinical models of cervical and ovarian cancer

    OpenAIRE

    Casagrande, Naike

    2014-01-01

    Cisplatin-based chemotherapy improves survival in cervical and ovarian cancer; however, treatment is associated with tumor resistance and significant toxicity. Lipoplatin (Regulon Inc., Mountain View, California) is a liposomal encapsulated form of cisplatin, developed in an effort to reduce cisplatin‟s systemic toxicity, while simultaneously improving the targeting of drugs to primary tumor and metastasis. Lipoplatin has been successfully administered in several randomized Phase II and II...

  13. Imaging diagnostics in ovarian cancer

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  14. p21 promotes oncolytic adenoviral activity in ovarian cancer and is a potential biomarker

    Directory of Open Access Journals (Sweden)

    Lockley Michelle

    2010-07-01

    Full Text Available Abstract The oncolytic adenovirus dl922-947 replicates selectively within and lyses cells with a dysregulated Rb pathway, a finding seen in > 90% human cancers. dl922-947 is more potent than wild type adenovirus and the E1B-deletion mutant dl1520 (Onyx-015. We wished to determine which host cell factors influence cytotoxicity. SV40 large T-transformed MRC5-VA cells are 3-logs more sensitive to dl922-947 than isogenic parental MRC5 cells, confirming that an abnormal G1/S checkpoint increases viral efficacy. The sensitivity of ovarian cancer cells to dl922-947 varied widely: IC50 values ranged from 51 (SKOV3ip1 to 0.03 pfu/cell (TOV21G. Cells sensitive to dl922-947 had higher S phase populations and supported earlier E1A expression. Cytotoxicity correlated poorly with both infectivity and replication, but well with expression of p21 by microarray and western blot analyses. Matched p21+/+ and -/- Hct116 cells confirmed that p21 influences dl922-947 activity in vitro and in vivo. siRNA-mediated p21 knockdown in sensitive TOV21G cells decreases E1A expression and viral cytotoxicity, whilst expression of p21 in resistant A2780CP cells increases virus activity in vitro and in intraperitoneal xenografts. These results highlight that host cell factors beyond simple infectivity can influence the efficacy of oncolytic adenoviruses. p21 expression may be an important biomarker of response in clinical trials.

  15. What Is Ovarian Cancer?

    Science.gov (United States)

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

  16. 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.

  17. What Are the Risk Factors for Ovarian Cancer?

    Science.gov (United States)

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

  18. Activation of platelet-activating factor receptor and pleiotropic effects on tyrosine phospho-EGFR/Src/FAK/paxillin in ovarian cancer.

    Science.gov (United States)

    Aponte, Margarita; Jiang, Wei; Lakkis, Montaha; Li, Ming-Jiang; Edwards, Dale; Albitar, Lina; Vitonis, Allison; Mok, Samuel C; Cramer, Daniel W; Ye, Bin

    2008-07-15

    Among the proinflammatory mediators, platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine) is a major primary and secondary messenger involved in intracellular and extracellular communication. Evidence suggests that PAF plays a significant role in oncogenic transformation, tumor growth, angiogenesis, and metastasis. However, PAF, with its receptor (PAFR) and their downstream signaling targets, has not been thoroughly studied in cancer. Here, we characterized the PAFR expression pattern in 4 normal human ovarian surface epithelial (HOSE) cell lines, 13 ovarian cancer cell lines, paraffin blocks (n = 84), and tissue microarrays (n = 230) from patients with ovarian cancer. Overexpression of PAFR was found in most nonmucinous types of ovarian cancer but not in HOSE and mucinous cancer cells. Correspondingly, PAF significantly induced cell proliferation and invasion only in PAFR-positive cells (i.e., OVCA429 and OVCA432), but not in PAFR-negative ovarian cells (HOSE and mucinous RMUG-L). The dependency of cell proliferation and invasion on PAFR was further confirmed using PAFR-specific small interfering RNA gene silencing probes, antibodies against PAFR and PAFR antagonist, ginkgolide B. Using quantitative multiplex phospho-antibody array technology, we found that tyrosine phosphorylation of EGFR/Src/FAK/paxillin was coordinately activated by PAF treatment, which was correlated with the activation of phosphatidylinositol 3-kinase and cyclin D1 as markers for cell proliferation, as well as matrix metalloproteinase 2 and 9 for invasion. Specific tyrosine Src inhibitor (PP2) reversibly blocked PAF-activated cancer cell proliferation and invasion. We suggest that PAFR is an essential upstream target of Src and other signal pathways to control the PAF-mediated cancer progression.

  19. Lactic dehydrogenase isozyme patterns and alpha-hydroxybutyrate dehydrogenase activities in serum from newborns, patients with ovarian cancer or myocardial infarction.

    Science.gov (United States)

    Kikuchi, Y; Kita, T; Furuya, K; Kato, K

    1988-11-01

    Lactic dehydrogenase (LDH) and alpha-hydroxybutyrate dehydrogenase (HBD) and LDH isozyme patterns were studied in serum from newborns and patients with ovarian cancer or myocardial infarction. LDH and HBD activities from newborns and patients with ovarian cancer or myocardial infarction were significantly increased, compared with those from patients with benign ovarian tumor. These increases were accompanied with a decrease of LDH-H and an increase of LDH-M in serum from newborns and patients with ovarian cancer, while an increase of LDH-H in serum from patients with myocardial infarction was dominant. However, the raised HBD activities in serum from patients with benign ovarian tumor did not affect the LDH isozyme patterns. From analysis of linear regression, a negative correlation between LDH-1 or -2 and HBD activity in serum from patients with ovarian cancer was observed while there was a positive correlation between LDH-4 and HBD activity. Similar patterns in serum from newborns were observed. On the other hand, a positive correlation between LDH-1 and HBD activity and a negative correlation between LDH-4 and HBD activity were found in serum from patients with myocardial infarction.

  20. Diindolylmethane suppresses ovarian cancer growth and potentiates the effect of cisplatin in tumor mouse model by targeting signal transducer and activator of transcription 3 (STAT3

    Directory of Open Access Journals (Sweden)

    Kandala Prabodh K

    2012-01-01

    Full Text Available Abstract Background Signal transducer and activator of transcription 3 (STAT3 is activated in majority of ovarian tumors and confers resistance to cisplatin treatment in patients with ovarian cancer. We have reported previously that diindolylmethane (DIM inhibits the growth of ovarian cancer cells. However, to date the exact mechanism by which DIM induces growth suppressive effects has not been clear. In this report the mode of action of DIM is investigated. Methods Six human ovarian cancer cell lines and an ovarian tumor xenograft animal model were used to study the effect of diindolylmethane alone or in combination with cisplatin. Results Diindolylmethane treatment induced apoptosis in all six ovarian cancer cell lines. Phosphorylation of STAT3 at Tyr-705 and Ser-727 was reduced by DIM in a concentration-dependent manner. In addition, diindolylmethane treatment inhibited nuclear translocation, DNA binding, and transcriptional activity of STAT3. Interleukin (IL-6-induced phosphorylation of STAT3 at Tyr-705 was significantly blocked by DIM. Overexpression of STAT3 by gene transfection blocked DIM-induced apoptosis. In addition, DIM treatment reduced the levels of IL-6 in ovarian cancer cells and in the tumors. DIM treatment also inhibited cell invasion and angiogenesis by suppressing hypoxia-inducible factor 1α (HIF-1α and vascular epithelial growth factor (VEGF. Importantly, diindolylmethane treatment potentiated the effects of cisplatin in SKOV-3 cells by targeting STAT3. Oral administration of 3 mg diindolylmethane per day and subsequent administration of cisplatin substantially inhibited in vivo tumor growth. Western blotting analysis of tumor lysates indicated increased apoptosis and reduced STAT3 activation. Conclusions These findings provide a rationale for further clinical investigation of DIM alone or in combination for chemoprevention and/or chemotherapy of ovarian cancer.

  1. A Blockade of IGF Signaling Sensitizes Human Ovarian Cancer Cells to the Anthelmintic Niclosamide-Induced Anti-Proliferative and Anticancer Activities

    Directory of Open Access Journals (Sweden)

    Youlin Deng

    2016-08-01

    Full Text Available Background/Aims: Ovarian cancer is the most lethal gynecologic malignancy, and there is an unmet clinical need to develop new therapies. Although showing promising anticancer activity, Niclosamide may not be used as a monotherapy. We seek to investigate whether inhibiting IGF signaling potentiates Niclosamide's anticancer efficacy in human ovarian cancer cells. Methods: Cell proliferation and migration are assessed. Cell cycle progression and apoptosis are analyzed by flow cytometry. Inhibition of IGF signaling is accomplished by adenovirus-mediated expression of siRNAs targeting IGF-1R. Cancer-associated pathways are assessed using pathway-specific reporters. Subcutaneous xenograft model is used to determine anticancer activity. Results: We find that Niclosamide is highly effective on inhibiting cell proliferation, cell migration, and cell cycle progression, and inducing apoptosis in human ovarian cancer cells, possibly by targeting multiple signaling pathways involved in ELK1/SRF, AP-1, MYC/MAX and NFkB. Silencing IGF-1R exert a similar but weaker effect than that of Niclosamide's. However, silencing IGF-1R significantly sensitizes ovarian cancer cells to Niclosamide-induced anti-proliferative and anticancer activities both in vitro and in vivo. Conclusion: Niclosamide as a repurposed anticancer agent may be more efficacious when combined with agents that target other signaling pathways such as IGF signaling in the treatment of human cancers including ovarian cancer.

  2. 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

  3. E-cadherin promotes proliferation of human ovarian cancer cells in vitro via activating MEK/ERK pathway

    Institute of Scientific and Technical Information of China (English)

    Ling-ling DONG; Lian LIU; Chun-hong MA; Ji-sheng LI; Chao DU; Shan XU; Li-hui HAN; Li LI; Xiu-wen WANG

    2012-01-01

    Aim:E-cadherin is unusually highly expressed in most ovarian cancers.This study was designed to investigate the roles of E-cadherin in the carcinogenesis and progression of ovarian cancers.Methods:Human ovarian adenocarcinoma cell line SKOV-3 was examined.E-cadherin gene CDH1 in SKOV-3 cells was knocked down via RNA interference (RNAi),and the resultant variation of biological behavior was observed using CCK-8 and colony formation experiment.E-cadherin-mediated Ca2+-dependent cell-cell adhesion was used to study the mechanisms underlying the effects of E-cadherin on the proliferation and survival of SKOV-3 cells.The expression levels of E-cadherin,extracellular signal-related kinase (ERK),phosphorylated ERK (P-ERK) were measured using Western blot assays.Results:Transfection with CDH1-siRNA for 24-96 h significantly suppressed the growth and proliferation of SKOV-3 cells.E-cadhednmediated calcium-dependent cell-cell adhesion of SKOV-3 cells resulted in a rapid increase of P-ERK,but did not modify the expression of ERK protein.The phosphorylation of ERK in the cells was blocked by pretreatment with the MEK1 specific inhibitor PD98059 (50μmol/L),but not bythe PI3K inhibitor wortmannin (1μmol/L) or PKA inhibitor H89 (10 μmol/L).Conclusion:E-cadherin may function as a tumor proliferation enhancer via activating the MEK/ERK pathway in development of ovarian epithelial cancers.

  4. 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.

  5. Ovarian cancer and body size

    DEFF Research Database (Denmark)

    Mosgaard, Berit Jul

    2012-01-01

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

  6. TLR activation of tumor-associated macrophages from ovarian cancer patients triggers cytolytic activity of NK cells.

    Science.gov (United States)

    Bellora, Francesca; Castriconi, Roberta; Dondero, Alessandra; Pessino, Anna; Nencioni, Alessio; Liggieri, Giovanni; Moretta, Lorenzo; Mantovani, Alberto; Moretta, Alessandro; Bottino, Cristina

    2014-06-01

    We analyzed the functional outcome of the interaction between tumor-associated macrophages (TAMs) and natural killer (NK) cells. TAMs from ascites of ovarian cancer patients displayed an alternatively activated functional phenotype (M2) characterized by a remarkably high frequency and surface density of membrane-bound IL-18. Upon TLR engagement, TAMs acquired a classically activated functional phenotype (M1), released immunostimulatory cytokines (IL-12, soluble IL-18), and efficiently triggered the cytolytic activity of NK cells. TAMs also induced the release of IFN-γ from NK cells, which however was significantly lower compared with that induced by in vitro-polarized M2 cells. Most tumor-associated NK cells displayed a CD56(bright) , CD16(neg) or CD56(bright) , CD16(dim) phenotype, and very poor cytolytic activities, despite an increased expression of the activation marker CD69. They also showed downregulation of DNAM-1, 2B4, and NTB-A activating receptors, and an altered chemokine receptor repertoire. Importantly however, when appropriately stimulated, NK cells from the patients, including those cells isolated from ascites, efficiently killed autologous TAMs that expressed low, "nonprotective" levels of HLA class I molecules. Overall, our data show the existence of a complex tumor microenvironment in which poorly cytolytic/immature NK cells deal with immunosuppressive tumor-educated macrophages.

  7. The Activities and Impact of State Programs to Address Hereditary Breast and Ovarian Cancer, 2011–2014

    Directory of Open Access Journals (Sweden)

    Katrina F. Trivers

    2015-10-01

    Full Text Available In 2011, the Division of Cancer Prevention and Control (DCPC, at the United States Centers for Disease Control and Prevention (CDC, released a three-year funding opportunity announcement (FOA for a competitive, non-research cooperative agreement. The agreement enhanced the capacities of state health departments to promote the application of best practices for evidence-based breast cancer genomics through education, surveillance, and policy activities. The FOA required that applicants focus on activities related to hereditary breast and ovarian cancer (HBOC. The DCPC funded three states: Georgia, Michigan, and Oregon. Georgia was a first-time recipient of cancer genomics funding, whereas Michigan and Oregon had long standing activities in cancer genomics and had received CDC funding in the past. By the end of the funding period, each state had well-functioning and impactful state-based programs in breast cancer genomics. This article highlights the impact of a few key state activities by using CDC’s Science Impact Framework. There were challenges to implementing public health genomics programs, including the need to develop relevant partnerships, the highly technical nature of the subject matter, a lack of genetic services in certain areas, and the difficulty in funding genetic services. Georgia, Michigan, and Oregon have served as models for others interested in initiating or expanding cancer genomics programs, and they helped to determine what works well for promoting and integrating public health genomics into existing systems.

  8. Hereditary breast and ovarian cancer

    DEFF Research Database (Denmark)

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

    2016-01-01

    Genetic abnormalities in the DNA repair genes BRCA1 and BRCA2 predispose to hereditary breast and ovarian cancer (HBOC). However, only approximately 25% of cases of HBOC can be ascribed to BRCA1 and BRCA2 mutations. Recently, exome sequencing has uncovered substantial locus heterogeneity among...... of putative causal variants and the clinical application of new HBOC genes in cancer risk management and treatment decision-making....

  9. Dihydroartemisinin is an inhibitor of ovarian cancer cell growth

    Institute of Scientific and Technical Information of China (English)

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

    2007-01-01

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

  10. Ovarian and tubal cancer in Denmark

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  11. Cytotoxic Activity from Curcuma zedoaria Through Mitochondrial Activation on Ovarian Cancer Cells.

    Science.gov (United States)

    Shin, Yujin; Lee, Yongkyu

    2013-12-31

    α-Curcumene is one of the physiologically active components of Curcuma zedoaria, which is believed to perform anti-tumor activities, the mechanisms of which are poorly understood. In the present study, we investigated the mechanism of the apoptotic effect of α-curcumene on the growth of human overian cancer, SiHa cells. Upon treatment with α-curcumene, cell viability of SiHa cells was inhibited > 73% for 48 h incubation. α-Curcumene treatment showed a characteristic nucleosomal DNA fragmentation pattern and the percentage of sub-diploid cells was increased in a concentration-dependent manner, hallmark features of apoptosis. Mitochondrial cytochrome c activation and an in vitro caspase-3 activity assay demonstrated that the activation of caspases accompanies the apoptotic effect of α-curcumene, which mediates cell death. These results suggest that the apoptotic effect of α-curcumene on SiHa cells may converge caspase-3 activation through the release of mitochondrial cytochrome c.

  12. 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...

  13. Ovarian cancer immunotherapy: opportunities, progresses and challenges

    Directory of Open Access Journals (Sweden)

    Stevens Richard

    2010-02-01

    Full Text Available Abstract Due to the low survival rates from invasive ovarian cancer, new effective treatment modalities are urgently needed. Compelling evidence indicates that the immune response against ovarian cancer may play an important role in controlling this disease. We herein summarize multiple immune-based strategies that have been proposed and tested for potential therapeutic benefit against advanced stage ovarian cancer. We will examine the evidence for the premise that an effective therapeutic vaccine against ovarian cancer is useful not only for inducing remission of the disease but also for preventing disease relapse. We will also highlight the questions and challenges in the development of ovarian cancer vaccines, and critically discuss the limitations of some of the existing immunotherapeutic strategies. Finally, we will summarize our own experience on the use of patient-specific tumor-derived heat shock protein-peptide complex for the treatment of advanced ovarian cancer.

  14. Evaluation of active hexose correlated compound (AHCC in combination with pegylated liposomal doxorubicin for treatment of ovarian cancer

    Directory of Open Access Journals (Sweden)

    R J Hunter

    2011-09-01

    Full Text Available Summary: The objective was to define the mechanism of the growth inhibition of active hexose correlated compound (AHCC alone and evaluate its activity in combination with pegylated liposomal doxorubicin (PLD. Scientific Methods: In vitro growth inhibition assays were completed with AHCC alone and in combination with PLD in panel of human cancer cell lines  and findings confirmed in vivo in an ovarian cancer xenograft mouse model.  AHCC mechanism of action was evaluated with immunoblotting and flow cytometry studies. Major Findings: The in vitro growth inhibition assays demonstrated additive activity when AHCC is co-administered with PLD.  The combination of AHCC with PLD demonstrated a 64.1% reduction in tumor growth compared to the untreated group (p value = 0.03 and a 31.2% improvement in tumor response with combination regimen compared to PLD alone. No difference in toxicity was observed in the control or treatment groups.  An increased expression of Bcl-2 was observed and induction of apoptosis confirmed in presence of AHCC. Conclusions: There is potential improvement in PLD activity when co-administered with AHCC and decrease side effects of PLD.  A clinical study to evaluate of the combination of AHCC plus PLD in the treatment of ovarian cancer is being pursued. Industrial Relevance: This study presents an example of the successful integration of a well- known herbal supplement, AHCC, with traditional western medicine cytotoxic agent, pegylated liposomal doxorubicin, for the treatment of recurrent ovarian cancer.    In addition to providing evidence of the efficacy of AHCC, the mechanism of improved activity was also investigated.   Using a traditional approach this study provides pre-clinical data to support the benefits previously observed and reported in the clinical setting and supports future endeavors to integrate AHCC into standard of care to be given with chemotherapy. .  These finding are particularly beneficial in the

  15. 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

  16. 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...

  17. Cisplatin induced apoptosis of ovarian cancer A2780s cells by activation of ERK/p53/PUMA signals.

    Science.gov (United States)

    Song, Hao; Wei, Mei; Liu, Wenfen; Shen, Shulin; Li, Jiaqun; Wang, Liming

    2017-03-13

    Cisplatin (CDDP) is one of the most effective anticancer agents widely used in the treatment of solid tumors, including ovarian cancer. It is generally considered as a cytotoxic drug which kills cancer cells by causing DNA damage, and subsequently inducing apoptosis in cancer cells. However, the underlying mechanisms leading to cell apoptosis remain obscure. In this study, the signaling pathways involved in CDDP -induced apoptosis were examined using CDDP-sensitive ovarian cancer A2780s cells. A2780s cells were treated with CDDP (1.5-3 μg/ml) for 6 h, 12 h and 24 h. Using siRNA targeting P53 and PUMA, and a selective MEK inhibitor, PD98059 to examine the relation between ERK1/2 activation, p53 and PUMA expression after exposure to CDDP, and the effect on CDDP-induced apoptosis. The results shown that treatment of A2780s cells with CDDP (3 μg/ml) for 6-24 h induced apoptosis, resulting in the activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and accumulation of p53 and PUMA (p53 upregulated modulator of apoptosis) protein. Knockdown of P53 or PUMA by siRNA transfection blocked CDDP-induced apoptosis. Inhibition of ERK1/2 using PD98059, a selective MEK inhibitor, blocked the apoptotic cell death but prevented CDDP-induced accumulation of p53 and PUMA. Knockdown of P53 by siRNA transfection also blocked CDDP-induced accumulation of PUMA. We therefore concluded that CDDP activated ERK1/2 and induced-p53-dependent PUMA upregulation, resulting in triggering apoptosis in A2780s cells. Our study clearly demonstrates that the ERK1/2/p53/PUMA axis is related to CDDP-induced cell death in A2780s cells.

  18. Chronic Recreational Physical Inactivity and Epithelial Ovarian Cancer Risk

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  19. Secreted Stress-Induced Phosphoprotein 1 Activates the ALK2-SMAD Signaling Pathways and Promotes Cell Proliferation of Ovarian Cancer Cells

    Directory of Open Access Journals (Sweden)

    Chia-Lung Tsai

    2012-08-01

    Full Text Available Stress-induced phosphoprotein 1 (STIP1, a cochaperone that organizes other chaperones, heat shock proteins (HSPs, was recently shown to be secreted by human ovarian cancer cells. In neuronal tissues, binding to prion protein was required for STIP1 to activate the ERK (extracellular-regulated MAP kinase signaling pathways. However, we report that STIP1 binding to a bone morphogenetic protein (BMP receptor, ALK2 (activin A receptor, type II-like kinase 2, was necessary and sufficient to stimulate proliferation of ovarian cancer cells. The binding of STIP1 to ALK2 activated the SMAD signaling pathway, leading to transcriptional activation of ID3 (inhibitor of DNA binding 3, promoting cell proliferation. In conclusion, ovarian-cancer-tissue-secreted STIP1 stimulates cancer cell proliferation by binding to ALK2 and activating the SMAD-ID3 signaling pathways. Although animal studies are needed to confirm these mechanisms in vivo, our results may pave the way for developing novel therapeutic strategies for ovarian cancer.

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

    Directory of Open Access Journals (Sweden)

    Ma YM

    2016-04-01

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

  1. Activity of chemotherapy in mucinous ovarian cancer with a recurrence free interval of more than 6 months: results from the SOCRATES retrospective study

    Directory of Open Access Journals (Sweden)

    Alletti Desiderio

    2008-09-01

    Full Text Available Abstract Background Mucinous ovarian carcinoma have a poorer prognosis compared with other histological subtypes. The aim of this study was to evaluate, retrospectively, the activity of chemotherapy in patients with platinum sensitive recurrent mucinous ovarian cancer. Methods The SOCRATES study retrospectively assessed the pattern of care of a cohort of patients with recurrent platinum-sensitive ovarian cancer observed in the years 2000–2002 in 37 Italian centres. Data were collected between April and September 2005. Patients with recurrent ovarian cancer with > 6 months of platinum free interval were considered eligible. Results Twenty patients with mucinous histotype and 388 patients with other histotypes were analyzed. At baseline, mucinous tumours differed from the others for an higher number of patients with lower tumor grading (p = 0.0056 and less advanced FIGO stage (p = 0.025. At time of recurrence, a statistically significant difference was found in performance status (worse in mucinous, p = 0.024. About 20% of patients underwent secondary cytoreduction in both groups, but a lower number of patients were optimally debulked in the mucinous group (p = 0.03. Patients with mucinous cancer received more frequently single agent platinum than platinum based-combination therapy or other non-platinum schedules as second line therapy (p = 0.026, with a response rate lower than in non-mucinous group (36.4% vs 62.6%, respectively, p = 0.04. Median time to progression and overall survival were worse for mucinous ovarian cancer. Finally, mucinous cancer received a lower number of chemotherapy lines (p = 0.0023. Conclusion This analysis shows that platinum sensitive mucinous ovarian cancer has a poor response to chemotherapy. Studies dedicated to this histological subgroup are needed.

  2. Experimental therapy of ovarian cancer with synthetic makaluvamine analog: in vitro and in vivo anticancer activity and molecular mechanisms of action.

    Directory of Open Access Journals (Sweden)

    Tao Chen

    Full Text Available The present study was designed to determine the biological effects of novel marine alkaloid analog 7-(4-fluorobenzylamino-1,3,4,8-tetrahydropyrrolo[4,3,2-de]quinolin-8(1H-one (FBA-TPQ on human ovarian cancer cells for its anti-tumor potential and the underlying mechanisms as a novel chemotherapeutic agent. Human ovarian cancer cells (A2780 and OVCAR-3, and Immortalized non-tumorigenic human Ovarian Surface Epithelial cells (IOSE-144, were exposed to FBA-TPQ for initial cytotoxicity evaluation (via MTS assay kit, Promega. The detailed in-vitro (cell level and in-vivo (animal model studies on the antitumor effects and possible underlying mechanisms of action of the compounds were then performed. FBA-TPQ exerted potent cytotoxicity against human ovarian cancer A2780 and OVCAR-3 cells as an effective inhibitor of cell growth and proliferation, while exerting lesser effects on non-tumorigenic IOSE-144 cells. Further study in the more sensitive OVCAR-3 cell line showed that it could potently induce cell apoptosis (Annexin V-FITC assay, G2/M cell cycle arrest (PI staining analysis and also dose-dependently inhibit OVCAR-3 xenograft tumors' growth on female athymic nude mice (BALB/c, nu/nu. Mechanistic studies (both in vitro and in vivo revealed that FBA-TPQ might exert its activity through Reactive Oxygen Species (ROS-associated activation of the death receptor, p53-MDM2, and PI3K-Akt pathways in OVCAR-3 cells, which is in accordance with in vitro microarray (Human genome microarrays, Agilent data analysis (GEO accession number: GSE25317. In conclusion, FBA-TPQ exhibits significant anticancer activity against ovarian cancer cells, with minimal toxicity to non-tumorigenic human IOSE-144 cells, indicating that it may be a potential therapeutic agent for ovarian cancer.

  3. A novel cisplatin mediated apoptosis pathway is associated with acid sphingomyelinase and FAS proapoptotic protein activation in ovarian cancer.

    Science.gov (United States)

    Maurmann, L; Belkacemi, L; Adams, N R; Majmudar, P M; Moghaddas, S; Bose, R N

    2015-07-01

    Platinum-based anticancer drugs, including cisplatin and carboplatin, have been cornerstones in the treatment of solid tumors. We report here that these DNA-damaging agents, particularly cisplatin, induce apoptosis through plasma membrane disruption, triggering FAS death receptor via mitochondrial (intrinsic) pathways. Our objectives were to: quantify the composition of membrane metabolites; and determine the potential involvement of acid sphingomyelinase (ASMase) in the FAS-mediated apoptosis in ovarian cancer after cisplatin treatment. The resulting analysis revealed enhanced apoptosis as measured by: increased phosphocholine, and glycerophosphocholine; elevated cellular energetics; and phosphocreatine and nucleoside triphosphate concentrations. The plasma membrane alterations were accompanied by increased ASMase activity, leading to the upregulation of FAS, FASL and related pro-apoptotic BAX and PUMA genes. Moreover FAS, FASL, BAX, PUMA, CASPASE-3 and -9 proteins were upregulated. Our findings implicate ASMase activity and the intrinsic pathways in cisplatin-mediated membrane demise, and contribute to our understanding of the mechanisms by which ovarian tumors may become resistant to cisplatin.

  4. Rethinking Ovarian Cancer: Recommendations for Improving Outcomes

    OpenAIRE

    2011-01-01

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

  5. 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....

  6. Changes in O-Linked N-Acetylglucosamine (O-GlcNAc) Homeostasis Activate the p53 Pathway in Ovarian Cancer Cells.

    Science.gov (United States)

    de Queiroz, Rafaela Muniz; Madan, Rashna; Chien, Jeremy; Dias, Wagner Barbosa; Slawson, Chad

    2016-09-02

    O-GlcNAcylation is a dynamic post-translational modification consisting of the addition of a single N-acetylglucosamine sugar to serine and threonine residues in proteins by the enzyme O-linked β-N-acetylglucosamine transferase (OGT), whereas the enzyme O-GlcNAcase (OGA) removes the modification. In cancer, tumor samples present with altered O-GlcNAcylation; however, changes in O-GlcNAcylation are not consistent between tumor types. Interestingly, the tumor suppressor p53 is modified by O-GlcNAc, and most solid tumors contain mutations in p53 leading to the loss of p53 function. Because ovarian cancer has a high frequency of p53 mutation rates, we decided to investigate the relationship between O-GlcNAcylation and p53 function in ovarian cancer. We measured a significant decrease in O-GlcNAcylation of tumor tissue in an ovarian tumor microarray. Furthermore, O-GlcNAcylation was increased, and OGA protein and mRNA levels were decreased in ovarian tumor cell lines not expressing the protein p53. Treatment with the OGA inhibitor Thiamet-G (TMG), silencing of OGA, or overexpression of OGA and OGT led to p53 stabilization, increased nuclear localization, and increased protein and mRNA levels of p53 target genes. These data suggest that changes in O-GlcNAc homeostasis activate the p53 pathway. Combination treatment of the chemotherapeutic cisplatin with TMG decreased tumor cell growth and enhanced cell cycle arrest without impairing cytotoxicity. The effects of TMG on tumor cell growth were partially dependent on wild type p53 activation. In conclusion, changes in O-GlcNAc homeostasis activate the wild type p53 pathway in ovarian cancer cells, and OGA inhibition has the potential as an adjuvant treatment for ovarian carcinoma.

  7. Specific TP53 Mutants Overrepresented in Ovarian Cancer Impact CNV, TP53 Activity, Responses to Nutlin-3a, and Cell Survival

    Directory of Open Access Journals (Sweden)

    Lisa K. Mullany

    2015-10-01

    Full Text Available Evolutionary Action analyses of The Cancer Gene Atlas data sets show that many specific p53 missense and gain-of-function mutations are selectively overrepresented and functional in high-grade serous ovarian cancer (HGSC. As homozygous alleles, p53 mutants are differentially associated with specific loss of heterozygosity (R273; chromosome 17; copy number variation (R175H; chromosome 9; and up-stream, cancer-related regulatory pathways. The expression of immune-related cytokines was selectively related to p53 status, showing for the first time that specific p53 mutants impact, and are related to, the immune subtype of ovarian cancer. Although the majority (31% of HGSCs exhibit loss of heterozygosity, a significant number (24% maintain a wild-type (WT allele and represent another HGSC subtype that is not well defined. Using human and mouse cell lines, we show that specific p53 mutants differentially alter endogenous WT p53 activity; target gene expression; and responses to nutlin-3a, a small molecular that activates WT p53 leading to apoptosis, providing “proof of principle” that ovarian cancer cells expressing WT and mutant alleles represent a distinct ovarian cancer subtype. We also show that siRNA knock down of endogenous p53 in cells expressing homozygous mutant alleles causes apoptosis, whereas cells expressing WT p53 (or are heterozygous for WT and mutant p53 alleles are highly resistant. Therefore, despite different gene regulatory pathways associated with specific p53 mutants, silencing mutant p53 might be a suitable, powerful, global strategy for blocking ovarian cancer growth in those tumors that rely on mutant p53 functions for survival. Knowing p53 mutational status in HGSC should permit new strategies tailored to control this disease.

  8. General Information about Ovarian Epithelial Cancer

    Science.gov (United States)

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

  9. 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.

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

    DEFF Research Database (Denmark)

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

    2009-01-01

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

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

    DEFF Research Database (Denmark)

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

    2009-01-01

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

  12. Radiation treatment of ovarian cancer

    Energy Technology Data Exchange (ETDEWEB)

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

    1982-03-01

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

  13. Identification of BRCA1-deficient ovarian cancers

    DEFF Research Database (Denmark)

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

    2011-01-01

    Objective. It is believed that 24 - 40% of ovarian cancers have dysfunction in the BRCA1 or BRCA2 (BRCAness) genes, either due to inherited or somatic mutations or due to epigenetic inactivation. Demonstration of ovarian cancers with BRCAness is becoming important both due to the possibility...... of offering genetic counseling and due to beneficial effects of PARP inhibitor treatment in this group. Since DNA sequencing is expensive and time-consuming efforts have been devoted to develop more indirect methods for BRCA screening that can improve the selection of patients for sequence-based BRCA testing....... Design. BRCA1-immunohistochemistry (IHC), fluorescence in-situ hybridization (FISH) and methylation analyses were performed on formalin-fixed, paraffin-embedded ovarian cancer tissue. Sample: 54 ovarian cancers; 15 BRCA1 cancers, 4 BRCA2 cancers, 10 cancers from patients with a family history...

  14. Predictive and therapeutic markers in ovarian cancer

    Science.gov (United States)

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

    2013-03-26

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

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

    Science.gov (United States)

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

    2012-01-01

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

  16. Hormone therapy and different ovarian cancers

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  17. Hormone therapy and different ovarian cancers

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  18. Cooperation of bisphenol A and leptin in inhibition of caspase-3 expression and activity in OVCAR-3 ovarian cancer cells.

    Science.gov (United States)

    Ptak, Anna; Rak-Mardyła, Agnieszka; Gregoraszczuk, Ewa L

    2013-09-01

    This study was designed to investigate the effect of bisphenol A and leptin on caspase-3 expression and activity in OVCAR-3 ovarian cancer cells. Caspase-3 and survivin expression was measured at the transcript level by real-time PCR and at the protein level by Western blotting. In addition, caspase-3 activity was measured, using a fluorometric assay, upon exposure to bisphenol A (40 nM) alone, leptin (2.5 nM) alone, and the combination of both agents. 17β-estradiol (40 nM) was used as a positive control for estrogenic properties of bisphenol A. Results showed that the interaction between bisphenol A and leptin, which was similar to that observed between 17β-estradiol and leptin, led to the inhibition of caspase-3 expression and activity in OVCAR-3 cells. Surprisingly, survivin was found to not be involved in the anti-apoptotic activity of either agent. Also, results showed that leptin inhibits caspase-3 activity by acting on the signal transducers and activators of transcription 3 (STAT3) pathway, but bisphenol A and 17β-estradiol by the extracellular-signal-regulated kinases 1/2 (ERK1/2) pathway. In conclusion, the study reveals that bisphenol A and leptin interact to inhibit caspase-3 expression and activity by modulating STAT3 and ERK1/2 signaling pathways in OVCAR-3 cells.

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

    Directory of Open Access Journals (Sweden)

    Enfeng Wang

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

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  1. 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.

  2. 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.

  3. Obesity and risk of ovarian cancer subtypes

    DEFF Research Database (Denmark)

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

    2013-01-01

    Whilst previous studies have reported that higher BMI increases a woman's risk of developing ovarian cancer, associations for the different histological subtypes have not been well defined. As the prevalence of obesity has increased dramatically, and classification of ovarian histology has improv...

  4. Imminent ovarian failure in childhood cancer survivors

    NARCIS (Netherlands)

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

    2006-01-01

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

  5. 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....

  6. Olaparib in the management of ovarian cancer

    Directory of Open Access Journals (Sweden)

    Bixel K

    2015-08-01

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

  7. Ovarian cancer in an interdisciplinary context

    DEFF Research Database (Denmark)

    Seibæk, Lene

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

  8. Inhibition of ALDH1A1 activity decreases expression of drug transporters and reduces chemotherapy resistance in ovarian cancer cell lines.

    Science.gov (United States)

    Januchowski, Radosław; Wojtowicz, Karolina; Sterzyńska, Karolina; Sosińska, Patrycja; Andrzejewska, Małgorzata; Zawierucha, Piotr; Nowicki, Michał; Zabel, Maciej

    2016-09-01

    The high mortality of ovarian cancer patients results from the failure of treatment caused by the inherent or acquired chemotherapy drug resistance. It was reported that overexpression of aldehyde dehydrogenase A1 (ALDH1A1) in cancer cells can be responsible for the development of drug resistance. To add the high expression of the drug transporter proteins the ALDHA1 is considered as a molecular target in cancer therapy. Therefore, we analysed drug-resistant ovarian cancer cell lines according to ALDHA1 expression and the association with drug resistance. The expression of ALDH1A1, P-glycoprotein (P-gp) or breast cancer resistance protein (BCRP) was determined using a microarray and confirmed by Q-PCR, western blot and fluorescence analysis. ALDH1A1 activity was determined using an Aldefluor assay. The impact of all-trans retinoic acid (ATRA) and diethylaminobenzaldehyde (DEAB) on chemotherapy resistance was assessed by the MTT chemosensitivity assay. The most abundant expression of ALDH1A1 was noted in paclitaxel- and topotecan-resistant cell lines where two populations of ALDH-positive and ALDH-negative cells could be observed. Those cell lines also revealed the overexpression of P-gp and BCRP respectively, and were able to form spheres in non-adherent conditions. Pre-treatment with ATRA and DEAB reduced chemotherapy resistance in both cell lines. ATRA treatment led to downregulation of the ALDH1A1, P-gp and BCRP proteins. DEAB treatment led to downregulation of the P-gp protein and BCRP transcript and protein. Our results indicate that ALDH1A1-positive cancer cells can be responsible for drug resistance development in ovarian cancer. Developing more specific ALDH1A1 inhibitors can increase chemotherapy effectiveness in ovarian cancer.

  9. Short-Term PTEN Inhibition Improves In Vitro Activation of Primordial Follicles, Preserves Follicular Viability, and Restores AMH Levels in Cryopreserved Ovarian Tissue From Cancer Patients.

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    Edurne Novella-Maestre

    Full Text Available In vitro activation and growth of primordial dormant follicles to produce fertilizable oocytes would provide a useful instrument for fertility preservation. The employment of Phosphatase and TENsin homolog (PTEN inhibitors, in combination with Protein kinase B (Akt stimulating molecules, has been previously employed to increase follicular activation through the stimulation of the PTEN-Akt pathway.We aim to establish improved in vitro activation also for cancer patients whose ovarian tissue has already been cryopreserved. Fresh and previously cryopreserved human ovarian cortex were exposed to short-term, low-concentration and ovary-specific treatment with only a PTEN inhibitor.Our in vitro activation protocol enhances the activation mechanisms of primordial follicles in both fresh and cryopreserved samples, and enlarges growing populations without inducing apoptosis in either follicles or the surrounding stroma. Treatment augments estradiol secretion and restores the expression levels of the previously diminished Anti-Müllerian hormone by means of cryopreservation procedures. Genomic modulation of the relative expression of PTEN pathway genes was found in treated samples.The in vitro activation protocol offers new alternatives for patients with cryopreserved tissue as it increases the pool of viable activated follicles available for in vitro growth procedures. The combination of ovarian tissue cryopreservation and in vitro activation of primordial follicles, the main ovarian reserve component, will be a major advancement in fertility preservation.

  10. 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...

  11. Emerging drugs for ovarian cancer.

    Science.gov (United States)

    Kelland, Lloyd R

    2005-05-01

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

  12. Functional Proteomics-Based Ovarian Cancer Biomarkers

    Science.gov (United States)

    2010-11-01

    levels and regulation of stathmin in paclitaxel-resistant ovarian cancer cells." Oncogene 22.55 (2003): 8924-8930. 11  Bankaitis-Davis, Danute, et...activator of transcription 6, phosphorylated Not Valid 56 149 * STATHMIN Stathmin 1 Validated 83 75 10 Survivin (BIRC5)baculoviral IAP repeat...Y182 34 FOXO3A 75 STATHMIN 117 BAD.PS112 35 P27 76 4EBP1 118 ER.ALPHA. 36 JNK 77 MCL1 118 ER.ALPHA.PS167 37 TAU 78 MIFT 119 ER.ALPHA 38 GATA3 79

  13. Aqueous Extract of Paris polyphylla (AEPP Inhibits Ovarian Cancer via Suppression of Peroxisome Proliferator-Activated Receptor-Gamma Coactivator (PGC-1alpha

    Directory of Open Access Journals (Sweden)

    Chia-Woei Wang

    2016-06-01

    Full Text Available Chemotherapy, a major approach was used in carcinoma treatment, always involves the development of drug resistance as well as side-effects that affect the quality of patients’ lives. An association between epithelial-mesenchymal transition (EMT and chemotherapy resistance was established recently. We demonstrate in this paper that the aqueous extract of Paris polyphylla (AEPP—a traditional Chinese medicine—can be used in various cancer types for suppression of carcinogenesis. We evaluated the suppressions of EMT and mitochondrial activity by AEPP treatment in a high-glucose (HG induced-human ovarian carcinoma cell line (OVCAR-3 cells. The mitochondrial morphology was investigated using MitoTracker Deep Red FM staining. Our results indicated that AEPP reduced the viability of OVCAR-3 cells considerably through induction of apoptosis. However, this inhibitory potential of AEPP was attenuated by HG induction in OVCAR-3 cells. The levels of estrogen-related receptor (ERR-alpha activator and peroxisome proliferator-activated receptor-gamma coactivator (PGC-1alpha were elevated by HG induction, but were suppressed by AEPP treatment. Down-regulations of cell survival and EMT were oberved in OVCAR-3 cells through suppression of PGC-1alpha by AEPP treatment. These results were confirmed through PGC-1alpha knockdown and overexpression in OVCAR-3 cells. Thus, AEPP can be beneficial for treating ovarian cancer and has potential for development of an integrative cancer therapy against ovarian cancer proliferation, metastasis, and migration.

  14. Neoadjuvant chemotherapy as ovarian cancer treatment

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  15. Genetic and molecular changes in ovarian cancer

    Institute of Scientific and Technical Information of China (English)

    Robert L Hollis; Charlie Gourley

    2016-01-01

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

  16. Radiosensitivity profiles from a panel of ovarian cancer cell lines exhibiting genetic alterations in p53 and disparate DNA-dependent protein kinase activities

    Energy Technology Data Exchange (ETDEWEB)

    Langland, Gregory T.; Yannone, Steven M.; Langland, Rachel A.; Nakao, Aki; Guan, Yinghui; Long, Sydney B.T.; Vonguyen, Lien; Chen, David J.; Gray, Joe W; Chen, Fanqing

    2009-09-07

    The variability of radiation responses in ovarian tumors and tumor-derived cell lines is poorly understood. Since both DNA repair capacity and p53 status can significantly alter radiation sensitivity, we evaluated these factors along with radiation sensitivity in a panel of sporadic human ovarian carcinoma cell lines. We observed a gradation of radiation sensitivity among these sixteen lines, with a five-fold difference in the LD50 between the most radiosensitive and the most radioresistant cells. The DNA-dependent protein kinase (DNA-PK) is essential for the repair of radiation induced DNA double-strand breaks in human somatic cells. Therefore, we measured gene copy number, expression levels, protein abundance, genomic copy and kinase activity for DNA-PK in all of our cell lines. While there were detectable differences in DNA-PK between the cell lines, there was no clear correlation with any of these differences and radiation sensitivity. In contrast, p53 function as determined by two independent methods, correlated well with radiation sensitivity, indicating p53 mutant ovarian cancer cells are typically radioresistant relative to p53 wild-type lines. These data suggest that the activity of regulatory molecules such as p53 may be better indicators of radiation sensitivity than DNA repair enzymes such as DNAPK in ovarian cancer.

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

    Science.gov (United States)

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

    2014-01-01

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

  18. Prognostic factors in young ovarian cancer patients

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  19. IL-6 Receptor Isoforms and Ovarian Cancer

    Science.gov (United States)

    2013-01-01

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

  20. Matrix metalloproteinase-10 regulates stemness of ovarian cancer stem-like cells by activation of canonical Wnt signaling and can be a target of chemotherapy-resistant ovarian cancer

    Science.gov (United States)

    Mariya, Tasuku; Hirohashi, Yoshihiko; Torigoe, Toshihiko; Tabuchi, Yuta; Asano, Takuya; Saijo, Hiroshi; Kuroda, Takafumi; Yasuda, Kazuyo; Mizuuchi, Masahito; Saito, Tsuyoshi; Sato, Noriyuki

    2016-01-01

    Epithelial ovarian cancer (EOC) is one of the most lethal cancers in females. Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) have been reported to be origin of primary and recurrent cancers and to be resistant to several treatments. In this study, we identified matrix metalloproteinase-10 (MMP10) is expressed in CSCs/CICs of EOC. An immunohistochemical study revealed that a high expression level of MMP10 is a marker for poor prognosis and platinum resistance in multivariate analysis. MMP10 gene overexpression experiments and MMP10 gene knockdown experiments using siRNAs revealed that MMP10 has a role in the maintenance of CSCs/CICs in EOC and resistance to platinum reagent. Furthermore, MMP10 activate canonical Wnt signaling by inhibiting noncanonical Wnt signaling ligand Wnt5a. Therefore, MMP10 is a novel marker for CSCs/CICs in EOC and that targeting MMP10 is a novel promising approach for chemotherapy-resistant CSCs/CICs in EOC. PMID:27072580

  1. Preclinical in vivo activity of a combination gemcitabine/liposomal doxorubicin against cisplatin-resistant human ovarian cancer (A2780/CDDP).

    Science.gov (United States)

    Gallo, D; Fruscella, E; Ferlini, C; Apollonio, P; Mancuso, S; Scambia, G

    2006-01-01

    Both gemcitabine and liposomal doxorubicin are antineoplastic drugs with clinical activity in platinum-refractory ovarian cancer. The purpose of this study was to evaluate the antitumor activity of a combination gemcitabine/liposomal doxorubicin administered to athymic mice bearing cisplatin-resistant human ovarian cancer (A2780/CDDP) xenografts. Emphasis was on the use of very low doses of each drug and of different dosing schedules. Data obtained showed that combined treatment with 80 mg/kg gemcitabine and 15 mg/kg liposomal doxorubicin produced a significant enhancement of antitumor activity compared with monotherapy at the same doses of these agents. Noteworthy is the fact that the majority of xenograft-bearing animals receiving the combination therapy demonstrated a complete tumor regression at the end of the study. A similar trend was observed when doses of both drugs were reduced to 20 mg/kg gemcitabine and to 6 mg/kg liposomal doxorubicin. Again, three out of ten mice receiving the combination were tumor free at the end of the study. No significant differences were observed in antitumor activity when comparing the simultaneous vs the consecutive dosing schedule. Remarkably, no additive toxicity was observed in any experimental trials. These data encourage clinical trials to prove the advantages of this combination treatment with respect to the single-agent chemotherapy in platinum-refractory ovarian cancer patients.

  2. Symptoms Relevant to Surveillance for Ovarian Cancer.

    Science.gov (United States)

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

    2017-03-20

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

  3. Symptoms Relevant to Surveillance for Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Robert M. Ore

    2017-03-01

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

  4. Genomic analysis of epithelial ovarian cancer

    Institute of Scientific and Technical Information of China (English)

    John Farley; Laurent L Ozbun; Michael J Birrer

    2008-01-01

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

  5. MicroRNA activity profile in the ovarian cancer cell line OVCAR3 identifies a proapoptotic effect of miR-23a

    Directory of Open Access Journals (Sweden)

    Andikyan V

    2015-10-01

    Full Text Available Vaagn Andikyan,1 Gregory Mullokandov,2 Judith Agudo,2 Ravi Sachidanandam,3,4 David Fishman,1 Alessia Baccarini,2 Brian D Brown2,3 1Department of Obstetrics, Gynecology and Reproductive Science, 2Department of Genetics and Genomic Sciences, 3Tisch Cancer Institute, 4Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA Introduction: Molecular profiling has revealed that many microRNAs (miRNAs are highly expressed in ovarian carcinoma. However, it is not yet known which miRNAs are biologically active (ie, they suppress expression of a target gene in ovarian cancer cells. Here we set out to determine the most active miRNAs in ovarian cancer cells. Methods: We performed miRNA molecular profiling by quantitative polymerase chain reaction array, and measured miRNA activity using a library of sensor vectors for 291 different conserved miRNAs. We inhibited miR-23a activity using a lentiviral-based decoy, and measured the percentage of apoptotic cells by flow cytometry. Results: Our miRNA activity profiling identified 54 active miRNAs in OVCAR3 cells, and found that over 150 miRNAs had no detectable activity. To study the function of an active miRNA, we selected miR-23a for further analysis. We inhibited miR-23a in OVCAR3 cells using a decoy vector, and found that there was decreased cell death compared to control (7.4%±1.4% versus 11.2%±0.5%; P<0.05 when the cells were treated with cisplatin. Moreover, the percentage of apoptotic cells was significantly lower in miR-23a inhibited cells compared to control (2.3%±0.4% versus 9.4%±2.6%; P<0.05. Conclusion: This study identifies the active miRNAs in OVCAR3 cells, and suggests that miR-23a may help to regulate chemosensitivity of ovarian cancer cells. Keywords: ovarian cancer, OVCAR3, microRNA profiling, miR-23a, apoptosis

  6. Approaches to the detection of ovarian cancer

    DEFF Research Database (Denmark)

    Høgdall, Estrid

    2016-01-01

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

  7. Antitumor properties of salinomycin on cisplatin-resistant human ovarian cancer cells in vitro and in vivo: involvement of p38 MAPK activation.

    Science.gov (United States)

    Zhang, Bei; Wang, Xueya; Cai, Fengfeng; Chen, Weijie; Loesch, Uli; Zhong, Xiao Yan

    2013-04-01

    In order to search for alternative agents to overcome chemoresistance during the treatment of ovarian cancer, this study aimed to examine the anticancer effects and action mechanism of salinomycin, a selective inhibitor of cancer stem cells, on cisplatin-resistant human ovarian cancer cell lines in vitro and in vivo. The concentration- (0.01-200 µM) and time‑dependent (24-72 h) growth inhibitory effects of salinomycin were observed in the ovarian cancer cell lines OV2008, C13, A2780, A2780-cp, SKOV3 and OVCAR3, by measuring cell viability using the resazurin reduction assay. The IC50 (24 h) range of salinomycin on the six cell lines was found to be 1.7-7.4 µM. After cisplatin-resistant C13 cells were treated with salinomycin, the percentage of apoptotic cells determined by flow cytometry was significantly increased, in a concentration- and time‑dependent manner. However, no cell cycle arrest was detected in the G1/G0, S and G2/M phases in the salinomycin‑treated and control cells. The Bio-Plex phosphoprotein 5-plex assay (Akt, IκB-α, ERK1/2, JNK and p38 MAPK) demonstrated a marked time- and concentration‑dependent increase in the phosphorylation of p38 MAPK, subsequent to salinomycin treatment. Moreover, salinomycin significantly suppressed tumor growth in a tumor xenograft model. These findings suggested that salinomycin efficiently inhibits the cisplatin-resistant human ovarian cancer cell line growth through the induction of apoptosis, potentially associated with the p38 MAPK activation.

  8. HE4 Gene Overexpression in Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    A Shahi

    2016-03-01

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

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

    Science.gov (United States)

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

    2014-08-15

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

  10. 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

  11. Ovarian stimulation in patients with breast cancer.

    Science.gov (United States)

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

    2015-01-01

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

  12. Colon resection for ovarian cancer: intraoperative decisions.

    Science.gov (United States)

    Hoffman, Mitchel S; Zervose, Emmanuel

    2008-11-01

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

  13. Analysis of the Mitogen-activated protein kinase kinase 4 (MAP2K4 tumor suppressor gene in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Ryland Georgina L

    2011-05-01

    Full Text Available Abstract Background MAP2K4 is a putative tumor and metastasis suppressor gene frequently found to be deleted in various cancer types. We aimed to conduct a comprehensive analysis of this gene to assess its involvement in ovarian cancer. Methods We screened for mutations in MAP2K4 using High Resolution Melt analysis of 149 primary ovarian tumors and methylation at the promoter using Methylation-Specific Single-Stranded Conformation Polymorphism analysis of 39 tumors. We also considered the clinical impact of changes in MAP2K4 using publicly available expression and copy number array data. Finally, we used siRNA to measure the effect of reducing MAP2K4 expression in cell lines. Results In addition to 4 previously detected homozygous deletions, we identified a homozygous 16 bp truncating deletion and a heterozygous 4 bp deletion, each in one ovarian tumor. No promoter methylation was detected. The frequency of MAP2K4 homozygous inactivation was 5.6% overall, and 9.8% in high-grade serous cases. Hemizygous deletion of MAP2K4 was observed in 38% of samples. There were significant correlations of copy number and expression in three microarray data sets. There was a significant correlation between MAP2K4 expression and overall survival in one expression array data set, but this was not confirmed in an independent set. Treatment of JAM and HOSE6.3 cell lines with MAP2K4 siRNA showed some reduction in proliferation. Conclusions MAP2K4 is targeted by genetic inactivation in ovarian cancer and restricted to high grade serous and endometrioid carcinomas in our cohort.

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

    Science.gov (United States)

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

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  16. Know the Risks, Warning Signs of Ovarian Cancer

    Science.gov (United States)

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

  17. 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....

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

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

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

  19. 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.

  20. Possible pathogenetic types of sporadical ovarian cancer

    Directory of Open Access Journals (Sweden)

    L. A. Ashrafyan

    2012-01-01

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

  1. Hedgehog signaling pathway and ovarian cancer

    Institute of Scientific and Technical Information of China (English)

    Qi Chen; Guolan Gao; Shiwen Luo

    2013-01-01

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

  2. TAp73-mediated the activation of c-Jun N-terminal kinase enhances cellular chemosensitivity to cisplatin in ovarian cancer cells.

    Directory of Open Access Journals (Sweden)

    Pingde Zhang

    Full Text Available P73, one member of the tumor suppressor p53 family, shares highly structural and functional similarity to p53. Like p53, the transcriptionally active TAp73 can mediate cellular response to chemotherapeutic agents in human cancer cells by up-regulating the expressions of its pro-apoptotic target genes such as PUMA, Bax, NOXA. Here, we demonstrated a novel molecular mechanism for TAp73-mediated apoptosis in response to cisplatin in ovarian cancer cells, and that was irrespective of p53 status. We found that TAp73 acted as an activator of the c-Jun N-terminal kinase (JNK signaling pathway by up-regulating the expression of its target growth arrest and DNA-damage-inducible protein GADD45 alpha (GADD45α and subsequently activating mitogen-activated protein kinase kinase-4 (MKK4. Inhibition of JNK activity by a specific inhibitor or small interfering RNA (siRNA significantly abrogated TAp73-mediated apoptosis induced by cisplatin. Furthermore, inhibition of GADD45α by siRNA inactivated MKK4/JNK activities and also blocked TAp73-mediated apoptosis induction by cisplatin. Our study has demonstrated that TAp73 activated the JNK apoptotic signaling pathway in response to cisplatin in ovarian cancer cells.

  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. Aurora-A Oncogene in Human Ovarian Cancer

    Science.gov (United States)

    2006-11-01

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

  5. CDK5 Regulates Paclitaxel Sensitivity in Ovarian Cancer Cells by Modulating AKT Activation, p21Cip1- and p27Kip1-Mediated G1 Cell Cycle Arrest and Apoptosis.

    Directory of Open Access Journals (Sweden)

    Shu Zhang

    Full Text Available Cyclin-dependent kinase 5 (CDK5 is a cytoplasmic serine/ threonine kinase. Knockdown of CDK5 enhances paclitaxel sensitivity in human ovarian cancer cells. This study explores the mechanisms by which CDK5 regulates paclitaxel sensitivity in human ovarian cancers. Multiple ovarian cancer cell lines and xenografts were treated with CDK5 small interfering RNA (siRNA with or without paclitaxel to examine the effect on cancer cell viability, cell cycle arrest and tumor growth. CDK5 protein was measured by immunohistochemical staining of an ovarian cancer tissue microarray to correlate CDK5 expression with overall patient survival. Knockdown of CDK5 with siRNAs inhibits activation of AKT which significantly correlates with decreased cell growth and enhanced paclitaxel sensitivity in ovarian cancer cell lines. In addition, CDK5 knockdown alone and in combination with paclitaxel induced G1 cell cycle arrest and caspase 3 dependent apoptotic cell death associated with post-translational upregulation and nuclear translocation of TP53 and p27(Kip1 as well as TP53-dependent transcriptional induction of p21(Cip1 in wild type TP53 cancer cells. Treatment of HEYA8 and A2780 wild type TP53 xenografts in nu/nu mice with CDK5 siRNA and paclitaxel produced significantly greater growth inhibition than either treatment alone. Increased expression of CDK5 in human ovarian cancers correlates inversely with overall survival. CDK5 modulates paclitaxel sensitivity by regulating AKT activation, the cell cycle and caspase-dependent apoptosis. CDK5 inhibition can potentiate paclitaxel activity in human ovarian cancer cells.

  6. Effect of ginsenoside Rh-2 via activation of caspase-3 and Bcl-2-insensitive pathway in ovarian cancer cells.

    Science.gov (United States)

    Kim, Jin Hee; Choi, Jae-Sun

    2016-12-13

    Ginsenoside has been reported to have therapeutic effects for some types of cancer, but its effect on ovarian cancer cells has not been evaluated. In this study, we monitored the effects of ginsenoside-Rh2 (Rh2) on the inhibition of cell proliferation and the apoptotic process in the ovarian cancer cell line SKOV3 using an MTT assay and TUNEL assay. We found that Rh2 inhibited cell proliferation and significantly induced apoptosis. We confirmed the apoptotic effects of Rh2 using western blot analysis of apoptosis-related proteins. Specifically, the levels of cleaved poly ADP ribose polymerase (PARP) and cleaved caspase-3 significantly increased in SKOV3 cells treated with Rh2. Therefore, Rh2 clearly suppressed the growth of SKOV3 cells in vitro, which was associated with induction of the apoptosis pathway. Moreover, the migration assay showed that Rh2 inhibited the invasive ability of SKOV3 cells. Taken together, our results suggest that Rh2 has anticancer effects in SKOV3 cells through inhibition of cell proliferation and induction of apoptosis. Considering the therapeutic potential of Rh2, more studies should be carried out to facilitate the future application of this natural product as a potential anti-cancer agent.

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

    Directory of Open Access Journals (Sweden)

    Ghislain Vanessa

    2008-01-01

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

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

    NARCIS (Netherlands)

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

    2003-01-01

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

  9. Noscapine Increases the Sensitivity of Drug-Resistant Ovarian Cancer Cell Line SKOV3/DDP to Cisplatin by Regulating Cell Cycle and Activating Apoptotic Pathways.

    Science.gov (United States)

    Shen, Wei; Liang, Bingfeng; Yin, Jie; Li, Xiurong; Cheng, Jianxin

    2015-05-01

    Cisplatin is a first-line chemotherapy drug against ovarian cancer. However, its strong toxic side effects and the development of cisplatin resistance in human cancer cells seriously influence the effects of chemotherapy and quality of life in patients. Noscapine (Nos), a non-toxic benzylisoquinoline alkaloid extracted from opium, has been recently reported to have anti-cancer activity, but the mechanism of that effect has not been clearly established. In the present study, we investigated cytotoxicity of Nos in combination with cisplatin (DDP) in drug-resistant human ovarian cancer cell line SKOV3/DDP in vitro and in vivo null mice xenograft model. Cell proliferation was measured by MTT assay, flow cytometry was used to analyze cell cycle and apoptosis, protein expression of several apoptotic factors was investigated by flow cytometry and immunohistochemical method, and their mRNA expression levels were determined by real-time PCR. In vitro experiments showed that Nos significantly inhibited proliferation of SKOV3/DDP cells. DDP/Nos-combined treatment notably enhanced DDP-induced inhibition of cell proliferation and increased the pro-apoptotic effect of DDP in SKOV3/DDP cells. DDP/Nos administration increased the proportion of G2/M cells, reduced both protein and mRNA expression of anti-apoptotic factors XIAP, surviving and NF-kB, and augmented protein and mRNA levels of pro-apoptotic caspase-3. In vivo experiments revealed that Nos/DDP treatment increased the apoptotic rate of xenograft tumors in null mice. Tumor volume decreased from 1.733 ± 0.155 g in mice treated with DDP alone to 1.191 ± 0.106 g in animals treated with Nos/DDP. These observations suggest that Nos increases the anti-cancer activity of DDP against the drug-resistant ovarian cancer cell line SKOV3/DDP by modulating the cell cycle and activating apoptotic pathways. The study provides a new chemotherapy strategy for the treatment of DDP-resistant human ovarian cancer.

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

    Science.gov (United States)

    Zhou, Xinling; Teng, Lingling; Wang, Min

    2016-05-01

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

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

    Science.gov (United States)

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

    2010-12-01

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

  12. Reprogramming of the Ovarian Tumor Stroma by Activation of a Biomechanical ECM Switch

    Science.gov (United States)

    2015-07-01

    AWARD NUMBER: W81XWH-14-1-0178 TITLE: Reprogramming of the Ovarian Tumor Stroma by Activation of a Biomechanical ECM Switch PRINCIPAL...CONTRACT NUMBER W81XWH-14-1-0178 Reprogramming of the Ovarian Tumor Stroma by Activation of a Biomechanical ECM Switch 5b. GRANT NUMBER 5c. PROGRAM...P130Cas, Ovarian carcinoma, Cancer associated fibroblasts. Running Title: HU177 epitope regulates ovarian tumor growth Financial Support: This work

  13. 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

  14. Pegylated liposomal doxorubicin in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Robert Strother

    2009-08-01

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

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

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

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

  16. Ovarian cancer treatment: The end of empiricism?

    Science.gov (United States)

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

    2015-09-15

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

  17. Regulatory T Cells in Human Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Dong-Jun Peng

    2012-01-01

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

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

    Science.gov (United States)

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

    2015-09-01

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

  19. Survival of ovarian cancer patients in Denmark

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  20. ACTIVATION OF PHOSPHATIDYLCHOLINE-SPECIFIC PHOSPHOLIPASE C IN BREAST AND OVARIAN CANCER:IMPACT ON MRS-DETECTED CHOLINE METABOLIC PROFILE AND PERSPECTIVES FOR TARGETED THERAPY

    Directory of Open Access Journals (Sweden)

    Franca Podo

    2016-08-01

    Full Text Available Elucidation of molecular mechanisms underlying the aberrant phosphatidylcholine-cycle in cancer cells plays in favor of the use of metabolic imaging in oncology and opens the way for designing new targeted therapies. The anomalous choline metabolic profile detected in cancer by magnetic resonance spectroscopy (MRS and spectroscopic imaging (MRSI provides molecular signatures of tumor progression and response to therapy.The increased level of intracellular phosphocholine (PCho typically detected in cancer cells is mainly attributed to upregulation of choline kinase, responsible for choline phosphorylation in the biosynthetic Kennedy pathway, but can also be partly produced by activation of phosphatidylcholine-specific phospholipase C (PC-PLC. This hydrolytic enzyme, known for implications in bacterial infection and in plant survival to hostile environmental conditions, is reported to be activated in mitogen- and oncogene-induced phosphatidylcholine cycles in mammalian cells, with effects on cell signaling, cell cycle regulation and cell proliferation.Recent investigations showed that PC-PLC activation could account for 20-to-50% of the intracellular PCho production in ovarian and breast cancer cells of different subtypes. Enzyme activation was associated with PC-PLC protein overexpression and subcellular redistribution in these cancer cells compared with non-tumoral counterparts. Moreover, PC-PLC co-immunoprecipitated with the human epidermal growth factor receptor-2 (HER2 and EGFR in HER2-overexpressing breast and ovarian cancer cells, while pharmacological PC-PLC inhibition resulted into long-lasting HER2 downregulation, retarded receptor re-expression on plasma membrane and anti-proliferative effects.This body of evidence points to PC-PLC as a potential target for newly designed therapies, whose effects can be pre-clinically and clinically monitored by metabolic imaging methods.

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

    Science.gov (United States)

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

    2011-01-01

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

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

    Science.gov (United States)

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

    2008-12-01

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

  3. Evaluating the ovarian cancer gonadotropin hypothesis

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  4. Menopausal hormone use and ovarian cancer risk

    DEFF Research Database (Denmark)

    Beral, V; Gaitskell, K; Hermon, C

    2015-01-01

    BACKGROUND: Half the epidemiological studies with information about menopausal hormone therapy and ovarian cancer risk remain unpublished, and some retrospective studies could have been biased by selective participation or recall. We aimed to assess with minimal bias the effects of hormone therap...

  5. Nuclear volume and prognosis in ovarian cancer

    DEFF Research Database (Denmark)

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

    1992-01-01

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

  6. Chemotherapy of ovarian cancer in elderly patients

    Institute of Scientific and Technical Information of China (English)

    Tiffany A. Troso-Sandoval; Stuart M. Lichtman

    2015-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    REN Juan; ZHANG Long

    2011-01-01

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

  8. Management of recurrent epithelial ovarian cancer

    Science.gov (United States)

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

    2014-01-01

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

  9. The progress of study on pathogenesis in ovarian cancer

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Shaheena Khan

    2010-01-01

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

  12. Genetics Home Reference: ovarian cancer

    Science.gov (United States)

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

  13. Current status of bevacizumab in advanced ovarian cancer

    Directory of Open Access Journals (Sweden)

    Tomao F

    2013-07-01

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

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

    Science.gov (United States)

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

  15. Targeting the Mevalonate Pathway to Reduce Mortality from Ovarian Cancer

    Science.gov (United States)

    2015-10-01

    AWARD NUMBER: W81XWH-14-1-0221 TITLE: Targeting the Mevalonate Pathway to Reduce Mortality from Ovarian Cancer PRINCIPAL INVESTIGATOR: Kala...AND SUBTITLE: Targeting the Meval onate Pathway to Reduce Mortality from Ovarian Cancer 5a. CONTRACT NUMBER W81XWH-14-1-0221 5b. GRANT NUMBER...cost. 15. SUBJECT TERMS: cancer mortality, cholesterol-lowering drugs, disease progression, epithelial ovarian cancer , lovastatin, Mevalonate Pathway

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  17. FAU regulates carboplatin resistance in ovarian cancer.

    Science.gov (United States)

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

    2010-01-01

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

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

    Science.gov (United States)

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

    2014-09-01

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

  19. Neoadjuvant chemotherapy as ovarian cancer treatment

    DEFF Research Database (Denmark)

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

    2012-01-01

    INTRODUCTION: The traditional first-line treatment for patients with advanced ovarian cancer with primary debulking surgery (PDS) and adjuvant chemotherapy is controversial as some authors report a potential benefit from the alternative treatment with neoadjuvant chemotherapy (NACT) and interval...... debulking surgery. The aim of this study was to investigate the use of NACT in Denmark in regard to increased use and regional differences. MATERIAL AND METHODS: Stage IIIC and IV ovarian cancer patients treated in the five Danish tertiary referral centres in the 2005-2010-period were included. The study...... is based on validated data from The Danish Gynaecological Cancer Database. RESULTS: Of the 1,367 eligible patients 1,069 were treated with PDS and 298 with NACT. In 2005-2007, 11% of patients were treated with NACT. In 2008-2010, this percentage had risen to 30% (p

  20. YY1 modulates taxane response in epithelial ovarian cancer

    Energy Technology Data Exchange (ETDEWEB)

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

    2008-10-10

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

  1. Current Research and Management of Ovarian Cancer in China

    Institute of Scientific and Technical Information of China (English)

    GUMeijiao; SHIWei

    2002-01-01

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

  2. Sex Steroid Hormone Receptor Expression Affects Ovarian Cancer Survival

    DEFF Research Database (Denmark)

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

    2015-01-01

    BACKGROUND AND AIMS: Although most ovarian cancers express estrogen (ER), progesterone (PR), and androgen (AR) receptors, they are currently not applied in clinical decision making. We explored the prognostic impact of sex steroid hormone receptor protein and mRNA expression on survival...... in epithelial ovarian cancer. METHODS: Immunohistochemical stainings for ERα, ERβ, PR, and AR were assessed in relation to survival in 118 serous and endometrioid ovarian cancers. Expression of the genes encoding the four receptors was studied in relation to prognosis in the molecular subtypes of ovarian cancer...... in ovarian cancer and support that tumors should be stratified based on molecular as well as histological subtypes in future studies investigating the role of endocrine treatment in ovarian cancer....

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  4. Effect of Amino Acids on the Generation of Ginsenoside Rg3 Epimers by Heat Processing and the Anticancer Activities of Epimers in A2780 Human Ovarian Cancer Cells

    Directory of Open Access Journals (Sweden)

    Jun Yeon Park

    2016-01-01

    Full Text Available Ginsenosides are the active components of Panax ginseng. Many research studies indicate that these deglycosylated, less-polar ginsenosides have better bioactivity than the major ginsenosides. In the present study, we sought to verify the enhanced anticancer effect of P. ginseng extract after undergoing the Maillard reaction as well as elucidate the underlying mechanism of action. The effects of 9 amino acids were tested; among them, the content of 20(S-Rg3 in the ginseng extract increased to more than 30, 20, and 20% when processed with valine, arginine, and alanine, respectively, compared with that after normal heat processing. The ginseng extract that was heat-processed with arginine exhibited the most potent inhibitory effect on A2780 ovarian cancer cell proliferation. Therefore, the generation of 20(S-Rg3 was suggested to be involved in this effect. Moreover, the inhibitory effect of 20(S-Rg3 on A2780 cell proliferation was significantly stronger than that of 20(R-Rg3. Protein expression levels of cleaved caspase-3, caspase-8, caspase-9, and PARP in the A2780 ovarian cancer cells markedly increased, whereas the expression of BID decreased after 20(S-Rg3 treatment. Therefore, we confirmed that the anticancer effects of the products of ginseng that was heat-processed with arginine are mediated mainly via the generation of the less-polar ginsenoside 20(S-Rg3.

  5. Residual ovarian activity during oral contraception

    NARCIS (Netherlands)

    A.M. van Heusden

    2003-01-01

    textabstractThe study objectives in this thesis focus on pituitary-ovarian activity in women using oral contraceptive steroids. Contraceptive steroids influence the hypothalamic-pituitary-ovarian axis in order to interfere with normal follicular development and ovulation. Additional effects on the e

  6. Targeting the tumour microenvironment in ovarian cancer.

    Science.gov (United States)

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

    2016-03-01

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

  7. Super p53 for Treatment of Ovarian Cancer

    Science.gov (United States)

    2016-07-01

    AWARD NUMBER: W81XWH-15-1-0036 TITLE: Super p53 for Treatment of Ovarian Cancer PRINCIPAL INVESTIGATOR: Carol S. Lim CONTRACTING...for Treatment of Ovarian Cancer 5b. GRANT NUMBER W81XWH-15-1 -0036 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER Carol S. Lim 5e...killing ovarian cancer cells in vitro. This is unreported, novel finding paves the way for using super p53 for ovarian cancer treatment . Main

  8. 77 FR 55095 - National Ovarian Cancer Awareness Month, 2012

    Science.gov (United States)

    2012-09-06

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

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

    Directory of Open Access Journals (Sweden)

    McClung EC

    2016-03-01

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

  10. 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.

  11. 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

  12. MicroRNAs and Recent Insights into Pediatric Ovarian Cancers

    Directory of Open Access Journals (Sweden)

    Jessica Anne Crawford

    2013-04-01

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

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

    Science.gov (United States)

    2016-05-01

    TERMS Obesity, Ovarian Cancer, ovarian stem cells, inflammation, adipose tissue 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18...transformed ovarian epithelial cells in obese animals. The goal is to identify genes and pathways that lead to ovarian cancer initiation and...progression. We also aim to identify secreted factors from adipose tissue that promote ovarian cancer initiation and progression in obesity

  14. 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...... 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....

  15. Epigenetic Characterization of Ovarian Cancer

    Science.gov (United States)

    2008-12-01

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

  16. Clinical Use of Cancer Biomarkers in Epithelial Ovarian Cancer

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  17. Deciphering the Adaptive Immune Response to Ovarian Cancer

    Science.gov (United States)

    2015-12-01

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

  18. Platelet adhesion and degranulation induce pro-survival and pro-angiogenic signalling in ovarian cancer cells.

    Directory of Open Access Journals (Sweden)

    Karl Egan

    Full Text Available Thrombosis is common in ovarian cancer. However, the interaction of platelets with ovarian cancer cells has not been critically examined. To address this, we investigated platelet interactions in a range of ovarian cancer cell lines with different metastatic potentials [HIO-80, 59M, SK-OV-3, A2780, A2780cis]. Platelets adhered to ovarian cancer cells with the most significant adhesion to the 59M cell line. Ovarian cancer cells induced platelet activation [P-selectin expression] in a dose dependent manner, with the most significant activation seen in response to the 59M cell line. The platelet antagonists [cangrelor, MRS2179, and apyrase] inhibited 59M cell induced activation suggesting a P2Y12 and P2Y1 receptor mediated mechanism of platelet activation dependent on the release of ADP by 59M cells. A2780 and 59M cells potentiated PAR-1, PAR-4, and TxA2 receptor mediated platelet activation, but had no effect on ADP, epinephrine, or collagen induced activation. Analysis of gene expression changes in ovarian cancer cells following treatment with washed platelets or platelet releasate showed a subtle but valid upregulation of anti-apoptotic, anti-autophagy pro-angiogenic, pro-cell cycle and metabolic genes. Thus, ovarian cancer cells with different metastatic potential adhere and activate platelets differentially while both platelets and platelet releasate mediate pro-survival and pro-angiogenic signals in ovarian cancer cells.

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

    Institute of Scientific and Technical Information of China (English)

    Hiroaki; Itamochi

    2010-01-01

    Ovarian cancer is the leading cause of death in women with gynecological cancer. Most patients are diagnosed at an advanced stage and have a poor prognosis.Currently, surgical tumor debulking, followed by platinum- and taxane-based chemotherapy is the standard treatment for advanced ovarian cancer. However, these patients are at great risk of recurrence and emerging drug resistance. Therefore, novel treatment strategies are required to improve outcomes for women with advanced ovarian cancer. A variety of molecular targeted agents, the majority of which are monoclonal antibodies and small-molecule protein-kinase inhibitors, have been explored in the management of ovarian cancer. The targets of these agents include angiogenesis, the human epidermal growth factor receptor family, ubiquitinproteasome pathway, epigenetic modulators, poly(ADPribose) polymerase (PARP), and mammalian target of rapamycin (mTOR) signaling pathway, which are aberrant in tumor tissue. The antiangiogenic agent, bevacizumab, has been reported as the most effective targeted agent and should be included in the standard chemotherapeutic regimen for advanced ovarian cancer. PARP inhibitors, which are mainly used in breast and ovarian cancer susceptibility gene-mutated patients, and mTOR inhibitors are also attractive treatment strategies, either alone or combination with chemotherapy, for ovarian cancer. Understanding the tumor molecular biology and identification of predictive biomarkers are essential steps for selection of the best treatment strategies. This article reviews the molecular mechanisms of the most promising targeted agents that are under early phase clinical evaluation for ovarian cancer.

  20. Mixed lineage kinase 3 is required for matrix metalloproteinase expression and invasion in ovarian cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhan, Yu; Abi Saab, Widian F.; Modi, Nidhi; Stewart, Amanda M. [Department of Biological Sciences, The University of Toledo, 2801 W. Bancroft, Toledo, OH 43606 (United States); Liu, Jinsong [Department of Pathology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030 (United States); Chadee, Deborah N., E-mail: deborah.chadee@utoledo.edu [Department of Biological Sciences, The University of Toledo, 2801 W. Bancroft, Toledo, OH 43606 (United States)

    2012-08-15

    Mixed lineage kinase 3 (MLK3) is a mitogen-activated protein kinase kinase kinase (MAP3K) that activates MAPK signaling pathways and regulates cellular responses such as proliferation, migration and apoptosis. Here we report high levels of total and phospho-MLK3 in ovarian cancer cell lines in comparison to immortalized nontumorigenic ovarian epithelial cell lines. Using small interfering RNA (siRNA)-mediated gene silencing, we determined that MLK3 is required for the invasion of SKOV3 and HEY1B ovarian cancer cells. Furthermore, mlk3 silencing substantially reduced matrix metalloproteinase (MMP)-1, -2, -9 and -12 gene expression and MMP-2 and -9 activities in SKOV3 and HEY1B ovarian cancer cells. MMP-1, -2, -9 and-12 expression, and MLK3-induced activation of MMP-2 and MMP-9 requires both extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) activities. In addition, inhibition of activator protein-1 (AP-1) reduced MMP-1, MMP-9 and MMP-12 gene expression. Collectively, these findings establish MLK3 as an important regulator of MMP expression and invasion in ovarian cancer cells. -- Highlights: Black-Right-Pointing-Pointer Ovarian cancer cell lines have high levels of total and phosphorylated MLK3. Black-Right-Pointing-Pointer MLK3 is required for MMP expression and activity in ovarian cancer cells. Black-Right-Pointing-Pointer MLK3 is required for invasion of SKOV3 and HEY1B ovarian cancer cells. Black-Right-Pointing-Pointer MLK3-dependent regulation of MMP-2 and MMP-9 activities requires ERK and JNK.

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

    Directory of Open Access Journals (Sweden)

    Michael P Stany

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

  2. Resveratrol, Acetyl-Resveratrol, and Polydatin Exhibit Antigrowth Activity against 3D Cell Aggregates of the SKOV-3 and OVCAR-8 Ovarian Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Simon J. Hogg

    2015-01-01

    Full Text Available Resveratrol has aroused significant scientific interest as it has been claimed that it exhibits a spectrum of health benefits. These include effects as an anti-inflammatory and an antitumour compound. The purpose of this study was to investigate and compare any potential antigrowth effects of resveratrol and two of its derivatives, acetyl-resveratrol and polydatin, on 3D cell aggregates of the EGFR/Her-2 positive and negative ovarian cancer cell lines SKOV-3 and OVCAR-8, respectively. Results showed that resveratrol and acetyl-resveratrol reduced cell growth in the SKOV-3 and OVCAR-8 in a dose-dependant manner. The growth reduction was mediated by the induction of apoptosis via the cleavage of poly(ADP-ribose polymerase (PARP-1. At lower concentrations, 5 and 10 µM, resveratrol, acetyl-resveratrol, and polydatin were less effective than higher concentrations, 50 and 100 µM. In SKOV-3 line, at higher concentrations, resveratrol and polydatin significantly reduced the phosphorylation of Her-2 and EGFR and the expression of Erk. Acetyl-resveratrol, on the other hand, did not change the activation of Her-2 and EGFR. Resveratrol, acetyl-resveratrol, and polydatin suppressed the secretion of VEGF in a dose-dependant fashion. In the OVCAR-8 cell line, resveratrol and acetyl-resveratrol at 5 and 10 µM increased the activation of Erk. Above these concentrations they decreased activation. Polydatin did not produce this effect. This study demonstrates that resveratrol and its derivatives may inhibit growth of 3D cell aggregates of ovarian cancer cell lines via different signalling molecules. Resveratrol and its derivatives, therefore, warrant further in vivo evaluation to assess their potential clinical utility.

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

    Directory of Open Access Journals (Sweden)

    Ahn Suzie E

    2010-08-01

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

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

    Directory of Open Access Journals (Sweden)

    Massimo Federico

    2013-04-01

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

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

    Science.gov (United States)

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

    2016-10-15

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

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  7. Vaccine-based clinical trials in ovarian cancer

    NARCIS (Netherlands)

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

    2011-01-01

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

  8. 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....

  9. 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....

  10. 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....

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

    Directory of Open Access Journals (Sweden)

    Vinod Vathipadiekal

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

  12. The Role of Mesenchymal Stem Cells in Promoting Ovarian Cancer Growth and Spread

    Science.gov (United States)

    2014-12-01

    home to tissue injury. Monocyte polarization into the classically activated pro- inflam - matory macrophages (M1) occurs early on in tissue repair, whereas...AWARD NUMBER: W81XWH-12-1-0438 TITLE: The Role of Mesenchymal Stem Cells in Promoting Ovarian Cancer Growth and Spread PRINCIPAL INVESTIGATOR...SUBTITLE The Role of Mesenchymal Stem Cells in Promoting Ovarian Cancer Growth and Spread 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-12-1-0438 5c

  13. Extracellular acidification activates ovarian cancer G-protein-coupled receptor 1 and GPR4 homologs of zebra fish

    Energy Technology Data Exchange (ETDEWEB)

    Mochimaru, Yuta [Laboratory of Cell Signaling Regulation, Department of Life Sciences, School of Agriculture, Meiji University, Kawasaki 214-8571 (Japan); Azuma, Morio [Laboratory of Regulatory Biology, Graduate School of Science and Engineering, University of Toyama, 3190 Gofuku, Toyama 930-8555 (Japan); Oshima, Natsuki; Ichijo, Yuta; Satou, Kazuhiro [Laboratory of Cell Signaling Regulation, Department of Life Sciences, School of Agriculture, Meiji University, Kawasaki 214-8571 (Japan); Matsuda, Kouhei [Laboratory of Regulatory Biology, Graduate School of Science and Engineering, University of Toyama, 3190 Gofuku, Toyama 930-8555 (Japan); Asaoka, Yoichi; Nishina, Hiroshi [Department of Developmental and Regenerative Biology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113-8510 (Japan); Nakakura, Takashi [Department of Anatomy, Graduate School of Medicine, Teikyo University, 2-11-1 Kaga Itabashi-Ku, Tokyo 173-8605 (Japan); Mogi, Chihiro; Sato, Koichi; Okajima, Fumikazu [Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512 (Japan); Tomura, Hideaki, E-mail: tomurah@meiji.ac.jp [Laboratory of Cell Signaling Regulation, Department of Life Sciences, School of Agriculture, Meiji University, Kawasaki 214-8571 (Japan)

    2015-02-20

    Mammalian ovarian G-protein-coupled receptor 1 (OGR1) and GPR4 are identified as a proton-sensing G-protein-coupled receptor coupling to multiple intracellular signaling pathways. In the present study, we examined whether zebra fish OGR1 and GPR4 homologs (zOGR1 and zGPR4) could sense protons and activate the multiple intracellular signaling pathways and, if so, whether the similar positions of histidine residue, which is critical for sensing protons in mammalian OGR and GPR4, also play a role to sense protons and activate the multiple signaling pathways in the zebra fish receptors. We found that extracellular acidic pH stimulated CRE-, SRE-, and NFAT-promoter activities in zOGR1 overexpressed cells and stimulated CRE- and SRE- but not NFAT-promoter activities in zGPR4 overexpressed cells. The substitution of histidine residues at the 12th, 15th, 162th, and 264th positions from the N-terminal of zOGR1 with phenylalanine attenuated the proton-induced SRE-promoter activities. The mutation of the histidine residue at the 78th but not the 84th position from the N-terminal of zGPR4 to phenylalanine attenuated the proton-induced SRE-promoter activities. These results suggest that zOGR1 and zGPR4 are also proton-sensing G-protein-coupled receptors, and the receptor activation mechanisms may be similar to those of the mammalian receptors. - Highlights: • Zebra fish OGR1 and GPR4 homologs (zOGR1, zGPR4) are proton-sensing receptors. • The signaling pathways activated by zOGR1 and zGPR4 are different. • Histidine residues critical for sensing protons are conserved.

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

    Science.gov (United States)

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

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

    Science.gov (United States)

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

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

    Science.gov (United States)

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2014-07-15

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

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

    Directory of Open Access Journals (Sweden)

    Rachel E Dickinson

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

  20. Extracellular acidification activates ovarian cancer G-protein-coupled receptor 1 and GPR4 homologs of zebra fish.

    Science.gov (United States)

    Mochimaru, Yuta; Azuma, Morio; Oshima, Natsuki; Ichijo, Yuta; Satou, Kazuhiro; Matsuda, Kouhei; Asaoka, Yoichi; Nishina, Hiroshi; Nakakura, Takashi; Mogi, Chihiro; Sato, Koichi; Okajima, Fumikazu; Tomura, Hideaki

    2015-02-20

    Mammalian ovarian G-protein-coupled receptor 1 (OGR1) and GPR4 are identified as a proton-sensing G-protein-coupled receptor coupling to multiple intracellular signaling pathways. In the present study, we examined whether zebra fish OGR1 and GPR4 homologs (zOGR1 and zGPR4) could sense protons and activate the multiple intracellular signaling pathways and, if so, whether the similar positions of histidine residue, which is critical for sensing protons in mammalian OGR and GPR4, also play a role to sense protons and activate the multiple signaling pathways in the zebra fish receptors. We found that extracellular acidic pH stimulated CRE-, SRE-, and NFAT-promoter activities in zOGR1 overexpressed cells and stimulated CRE- and SRE- but not NFAT-promoter activities in zGPR4 overexpressed cells. The substitution of histidine residues at the 12th, 15th, 162th, and 264th positions from the N-terminal of zOGR1 with phenylalanine attenuated the proton-induced SRE-promoter activities. The mutation of the histidine residue at the 78th but not the 84th position from the N-terminal of zGPR4 to phenylalanine attenuated the proton-induced SRE-promoter activities. These results suggest that zOGR1 and zGPR4 are also proton-sensing G-protein-coupled receptors, and the receptor activation mechanisms may be similar to those of the mammalian receptors.

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

    Science.gov (United States)

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

    2016-01-01

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

  2. 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.

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

    Science.gov (United States)

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

    2013-03-27

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

  4. 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.

  5. Obesity Exposure Across the Lifespan on Ovarian Cancer Pathogenesis

    Science.gov (United States)

    2015-08-01

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

  6. Screening for genes associated with ovarian cancer prognosis

    Institute of Scientific and Technical Information of China (English)

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

    2009-01-01

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

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

    Science.gov (United States)

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

    2005-01-01

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

  8. Identifying novel hypoxia-associated markers of chemoresistance in ovarian cancer.

    LENUS (Irish Health Repository)

    McEvoy, Lynda M

    2015-01-01

    Ovarian cancer is associated with poor long-term survival due to late diagnosis and development of chemoresistance. Tumour hypoxia is associated with many features of tumour aggressiveness including increased cellular proliferation, inhibition of apoptosis, increased invasion and metastasis, and chemoresistance, mostly mediated through hypoxia-inducible factor (HIF)-1α. While HIF-1α has been associated with platinum resistance in a variety of cancers, including ovarian, relatively little is known about the importance of the duration of hypoxia. Similarly, the gene pathways activated in ovarian cancer which cause chemoresistance as a result of hypoxia are poorly understood. This study aimed to firstly investigate the effect of hypoxia duration on resistance to cisplatin in an ovarian cancer chemoresistance cell line model and to identify genes whose expression was associated with hypoxia-induced chemoresistance.

  9. Locomotor proteins in tissues of primary tumors and metastases of ovarian and breast cancer

    Science.gov (United States)

    Kondakova, I. V.; Yunusova, N. V.; Spirina, L. V.; Shashova, E. E.; Kolegova, E. S.; Kolomiets, L. A.; Slonimskaya, E. M.; Villert, A. B.

    2016-08-01

    The paper discusses the capability for active movement in an extracellular matrix, wherein remodeling of the cytoskeleton by actin binding proteins plays a significant role in metastases formation. We studied the expression of actin binding proteins and β-catenin in tissues of primary tumors and metastases of ovarian and breast cancer. Contents of p45 Ser β-catenin and the actin severing protein gelsolin were decreased in metastases of ovarian cancer relative to primary tumors. The level of the cofilin, functionally similar to gelsolin, was significantly higher in metastases compared to primary ovarian and breast tumor tissue. In breast cancer, significant increase in the number of an actin monomer binder protein thymosin-β4 was observed in metastases as compared to primary tumors. The data obtained suggest the involvement of locomotor proteins in metastases formation in ovarian and breast cancer.

  10. BRCA somatic mutations and epigenetic BRCA modifications in serous ovarian cancer.

    Science.gov (United States)

    Moschetta, M; George, A; Kaye, S B; Banerjee, S

    2016-08-01

    The significant activity of poly(ADP-ribose)polymerase (PARP) inhibitors in the treatment of germline BRCA mutation-associated ovarian cancer, which represents ∼15% of HGS cases, has recently led to European Medicines Agency and food and drug administration approval of olaparib. Accumulating evidence suggests that PARP inhibitors may have a wider application in the treatment of sporadic ovarian cancers. Up to 50% of HGS ovarian cancer patients may exhibit homologous recombination deficiency (HRD) through mechanisms including germline BRCA mutations, somatic BRCA mutations, and BRCA promoter methylation. In this review, we discuss the role of somatic BRCA mutations and BRCA methylation in ovarian cancer. There is accumulating evidence for routine somatic BRCA mutation testing, but the relevance of BRCA epigenetic modifications is less clear. We explore the challenges that need to be addressed if the full potential of these markers of HRD is to be utilised in clinical practice.

  11. Surgery for advanced epithelial ovarian cancer.

    Science.gov (United States)

    Hacker, Neville F; Rao, Archana

    2016-10-20

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

  12. 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.

  13. Cells of Origin of Epithelial Ovarian Cancers

    Science.gov (United States)

    2015-09-01

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

  14. 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.

  15. Cancer Vaccines in Ovarian Cancer: How Can We Improve?

    Directory of Open Access Journals (Sweden)

    Silvia Martin Lluesma

    2016-05-01

    Full Text Available Epithelial ovarian cancer (EOC is one important cause of gynecologic cancer-related death. Currently, the mainstay of ovarian cancer treatment consists of cytoreductive surgery and platinum-based chemotherapy (introduced 30 years ago but, as the disease is usually diagnosed at an advanced stage, its prognosis remains very poor. Clearly, there is a critical need for new treatment options, and immunotherapy is one attractive alternative. Prophylactic vaccines for prevention of infectious diseases have led to major achievements, yet therapeutic cancer vaccines have shown consistently low efficacy in the past. However, as they are associated with minimal side effects or invasive procedures, efforts directed to improve their efficacy are being deployed, with Dendritic Cell (DC vaccination strategies standing as one of the more promising options. On the other hand, recent advances in our understanding of immunological mechanisms have led to the development of successful strategies for the treatment of different cancers, such as immune checkpoint blockade strategies. Combining these strategies with DC vaccination approaches and introducing novel combinatorial designs must also be considered and evaluated. In this review, we will analyze past vaccination methods used in ovarian cancer, and we will provide different suggestions aiming to improve their efficacy in future trials.

  16. Targeting of Topoisomerase I for Prognoses and Therapeutics of Camptothecin-Resistant Ovarian Cancer

    Science.gov (United States)

    Tsai, Hsiang-Ping; An, Herng-Wei; Lee, Chi-Ming; Wu, Jen-Chine; Chen, Chien-Shu; Huang, Shih-Hao; Hwang, Jaulang; Cheng, Kur-Ta; Leiw, Phui-Ly; Chen, Chi-Long; Lin, Chun-Mao

    2015-01-01

    DNA topoisomerase I (TOP1) levels of several human neoplasms are higher than those of normal tissues. TOP1 inhibitors are widely used in treating conventional therapy-resistant ovarian cancers. However, patients may develop resistance to TOP1 inhibitors, hampering chemotherapy success. In this study, we examined the mechanisms associated with the development of camptothecin (CPT) resistance in ovarian cancers and identified evodiamine (EVO), a natural product with TOP1 inhibiting activity that overcomes the resistance. The correlations among TOP1 levels, cancer staging, and overall survival (OS) were analyzed. The effect of EVO on CPT-resistant ovarian cancer was evaluated in vitro and in vivo. TOP1 was associated with poor prognosis in ovarian cancers (p = 0.024). EVO induced apoptosis that was detected using flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The tumor size decreased significantly in the EVO treatment group compared with the control group (p < 0.01) in a xenograft mouse model. Effects of drugs targeting TOP1 for prognosis and therapy in CPT-resistant ovarian cancer are anticipated. EVO with TOP1 can be developed as an antiproliferative agent for overcoming CPT resistance in ovarian cancers. PMID:26207989

  17. Targeting of Topoisomerase I for Prognoses and Therapeutics of Camptothecin-Resistant Ovarian Cancer.

    Directory of Open Access Journals (Sweden)

    Yu-Chieh Lee

    Full Text Available DNA topoisomerase I (TOP1 levels of several human neoplasms are higher than those of normal tissues. TOP1 inhibitors are widely used in treating conventional therapy-resistant ovarian cancers. However, patients may develop resistance to TOP1 inhibitors, hampering chemotherapy success. In this study, we examined the mechanisms associated with the development of camptothecin (CPT resistance in ovarian cancers and identified evodiamine (EVO, a natural product with TOP1 inhibiting activity that overcomes the resistance. The correlations among TOP1 levels, cancer staging, and overall survival (OS were analyzed. The effect of EVO on CPT-resistant ovarian cancer was evaluated in vitro and in vivo. TOP1 was associated with poor prognosis in ovarian cancers (p = 0.024. EVO induced apoptosis that was detected using flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL assay. The tumor size decreased significantly in the EVO treatment group compared with the control group (p < 0.01 in a xenograft mouse model. Effects of drugs targeting TOP1 for prognosis and therapy in CPT-resistant ovarian cancer are anticipated. EVO with TOP1 can be developed as an antiproliferative agent for overcoming CPT resistance in ovarian cancers.

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

    NARCIS (Netherlands)

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

    2011-01-01

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

  19. Ovarian Cancer Treatment | Cancer Trends Progress Report

    Science.gov (United States)

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

  20. Cediranib, an Oral Inhibitor of Vascular Endothelial Growth Factor Receptor Kinases, Is an Active Drug in Recurrent Epithelial Ovarian, Fallopian Tube, and Peritoneal Cancer

    Science.gov (United States)

    Matulonis, Ursula A.; Berlin, Suzanne; Ivy, Percy; Tyburski, Karin; Krasner, Carolyn; Zarwan, Corrine; Berkenblit, Anna; Campos, Susana; Horowitz, Neil; Cannistra, Stephen A.; Lee, Hang; Lee, Julie; Roche, Maria; Hill, Margaret; Whalen, Christin; Sullivan, Laura; Tran, Chau; Humphreys, Benjamin D.; Penson, Richard T.

    2009-01-01

    Purpose Angiogenesis is important for epithelial ovarian cancer (EOC) growth, and blocking angiogenesis can lead to EOC regression. Cediranib is an oral tyrosine kinase inhibitor (TKI) of vascular endothelial growth factor receptor (VEGFR) -1, VEGFR-2, VEGFR-3, and c-kit. Patients and Methods We conducted a phase II study of cediranib for recurrent EOC or peritoneal or fallopian tube cancer; cediranib was administered as a daily oral dose, and the original dose was 45 mg daily. Because of toxicities observed in the first 11 patients, the dose was lowered to 30 mg. Eligibility included ≤ two lines of chemotherapy for recurrence. End points included response rate (via Response Evaluation Criteria in Solid Tumors [RECIST] or modified Gynecological Cancer Intergroup CA-125), toxicity, progression-free survival (PFS), and overall survival (OS). Results Forty-seven patients were enrolled; 46 were treated. Clinical benefit rate (defined as complete response [CR] or partial response [PR], stable disease [SD] > 16 weeks, or CA-125 nonprogression > 16 weeks), which was the primary end point, was 30%; eight patients (17%; 95% CI, 7.6% to 30.8%) had a PR, six patients (13%; 95% CI, 4.8% to 25.7%) had SD, and there were no CRs. Eleven patients (23%) were removed from study because of toxicities before two cycles. Grade 3 toxicities (> 20% of patients) included hypertension (46%), fatigue (24%), and diarrhea (13%). Grade 2 hypothyroidism occurred in 43% of patients. Grade 4 toxicities included CNS hemorrhage (n = 1), hypertriglyceridemia/hypercholesterolemia/elevated lipase (n = 1), and dehydration/elevated creatinine (n = 1). No bowel perforations or fistulas occurred. Median PFS was 5.2 months, and median OS has not been reached; median follow-up time is 10.7 months. Conclusion Cediranib has activity in recurrent EOC, tubal cancer, and peritoneal cancer with predictable toxicities observed with other TKIs. PMID:19826113

  1. PPARγ inhibits ovarian cancer cells proliferation through upregulation of miR-125b

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Shuang, E-mail: luoshuangsch@163.com [Department of Obstetrics and Gynecology, Suining Central Hospital, Suining (China); Wang, Jidong [Department of Gynecology and Obsterics, Jinan Central Hospital, Jinan (China); Ma, Ying [Department of Otorhinolaryngolgy, Suining Central Hospital, Suining (China); Yao, Zhenwei [Department of Gynecology and Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing (China); Pan, Hongjuan [Department of Gynecology and Obsterics, Zhongshan Hospital, Wuhan (China)

    2015-06-26

    miR-125b has essential roles in coordinating tumor proliferation, angiogenesis, invasiveness, metastasis and chemotherapy recurrence. In ovarian cancer miR-125b has been shown to be downregulated and acts as a tumor suppressor by targeting proto-oncogene BCL3. PPARγ, a multiple functional transcription factor, has been reported to have anti-tumor effects through inhibition of proliferation and induction of differentiation and apoptosis by targeting the tumor related genes. However, it is unclear whether miR-125b is regulated by PPARγ in ovarian cancer. In this study, we demonstrated that the miR-125b downregulated in ovarian cancer tissues and cell lines. Ligands-activated PPARγ suppressed proliferation of ovarian cancer cells and this PPARγ-induced growth inhibition is mediated by the upregulation of miR-125b. PPARγ promoted the expression of miR-125b by directly binding to the responsive element in miR-125b gene promoter region. Thus, our results suggest that PPARγ can induce growth suppression of ovarian cancer by upregulating miR-125b which inhibition of proto-oncogene BCL3. These findings will extend our understanding of the function of PPARγ in tumorigenesis and miR-125b may be a therapeutic intervention of ovarian cancer. - Highlights: • miR-125b is down-regulated in ovarian cancer tissues and cells. • PPARγ upregulates miR-125b and downregulates its target gene BCL3 expression. • Silence of miR-125b attenuates PPARγ-mediated growth suppression of ovarian cancer cells. • PPARγ promotes the transcription of miR-125b via binding to PPARE in miR-125b gene promoter region.

  2. Consortium analysis of 7 candidate SNPs for ovarian cancer

    DEFF Research Database (Denmark)

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

    2008-01-01

    The Ovarian Cancer Association Consortium selected 7 candidate single nucleotide polymorphisms (SNPs), for which there is evidence from previous studies of an association with variation in ovarian cancer or breast cancer risks. The SNPs selected for analysis were F31I (rs2273535) in AURKA, N372H...... for SNPs identified from relatively large initial studies shows the importance of replicating associations by a consortium approach Udgivelsesdato: 2008/7/15...

  3. Protein kinase C alpha-CARMA3 signaling axis links Ras to NF-kappa B for lysophosphatidic acid-induced urokinase plasminogen activator expression in ovarian cancer cells.

    Science.gov (United States)

    Mahanivong, C; Chen, H M; Yee, S W; Pan, Z K; Dong, Z; Huang, S

    2008-02-21

    We reported previously that a signaling pathway consisting of G(i)-Ras-NF-kappaB mediates lysophosphatidic acid (LPA)-induced urokinase plasminogen activator (uPA) upregulation in ovarian cancer cells. However, it is not clear what signaling components link Ras to nuclear factor (NF)-kappaB for this LPA-induced event. In the present study, we found that treatment of protein kinase C (PKC) inhibitors including conventional PKC (cPKC) inhibitor Gö6976 abolished LPA-induced uPA upregulation in ovarian cancer cell lines tested, indicating the importance of cPKC activity in this LPA-induced event. Indeed, LPA stimulation led to the activation of PKCalpha and Ras-PKCalpha interaction. Although constitutively active mutants of PKCalpha (a cPKC), PKCtheta (a novel PKC (nPKC)) and PKCzeta (an atypical PKC (aPKC)) were all able to activate NF-kappaB and upregulate uPA expression, only dominant-negative PKCalpha mutant attenuated LPA-induced NF-kappaB activation and uPA upregulation. These results suggest that PKCalpha, rather than PKC isoforms in other PKC classes, participates in LPA-induced NF-kappaB activation and uPA upregulation in ovarian cancer cells. To determine the signaling components downstream of PKCalpha mediating LPA-induced uPA upregulation, we showed that forced expression of dominant-negative CARMA3 or silencing CARMA3, Bcl10 and MALT1 with specific siRNAs diminished these LPA-induced events. Furthermore, we demonstrated that PKCalpha/CARMA3 signaling axis is important in LPA-induced ovarian cancer cell in vitro invasion.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Li Jiang

    2014-06-01

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

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

    Science.gov (United States)

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

    2015-07-01

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

  8. Granisetron, Aprepitant, and Dexamethasone in Preventing Nausea and Vomiting in Patients Receiving Chemotherapy for Stage II, III, or IV Ovarian Cancer

    Science.gov (United States)

    2016-03-16

    Malignant Ovarian Mixed Epithelial Tumor; Nausea and Vomiting; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Stage II Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer; Undifferentiated Ovarian Carcinoma

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

    Directory of Open Access Journals (Sweden)

    Jimmy Belotte

    Full Text Available Ovarian cancer is the deadliest of all gynecologic cancers. Recent evidence demonstrates an association between enzymatic activity altering single nucleotide polymorphisms (SNP with human cancer susceptibility. We sought to evaluate the association of SNPs in key oxidant and antioxidant enzymes with increased risk and survival in epithelial ovarian cancer. Individuals (n = 143 recruited were divided into controls, (n = 94: healthy volunteers, (n = 18, high-risk BRCA1/2 negative (n = 53, high-risk BRCA1/2 positive (n = 23 and ovarian cancer cases (n = 49. DNA was subjected to TaqMan SNP genotype analysis for selected oxidant and antioxidant enzymes. Of the seven selected SNP studied, no association with ovarian cancer risk (Pearson Chi-square was found. However, a catalase SNP was identified as a predictor of ovarian cancer survival by the Cox regression model. The presence of this SNP was associated with a higher likelihood of death (hazard ratio (HR of 3.68 (95% confidence interval (CI: 1.149-11.836 for ovarian cancer patients. Kaplan-Meier survival analysis demonstrated a significant median overall survival difference (108 versus 60 months, p<0.05 for those without the catalase SNP as compared to those with the SNP. Additionally, age at diagnosis greater than the median was found to be a significant predictor of death (HR of 2.78 (95% CI: 1.022-7.578. This study indicates a strong association with the catalase SNP and survival of ovarian cancer patients, and thus may serve as a prognosticator.

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

    Directory of Open Access Journals (Sweden)

    Soheila Aminimoghaddam

    2016-04-01

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

  11. Enhancing the efficacy of cisplatin in ovarian cancer treatment – could arsenic have a role

    Directory of Open Access Journals (Sweden)

    Helm C William

    2009-01-01

    Full Text Available Abstract Ovarian cancer affects more than 200,000 women each year around the world. Most women are not diagnosed until the disease has already metastasized from the ovaries with a resultant poor prognosis. Ovarian cancer is associated with an overall 5 year survival of little more than 50%. The mainstay of front-line therapy is cytoreductive surgery followed by chemotherapy. Traditionally, this has been by the intravenous route only but there is more interest in the delivery of intraperitoneal chemotherapy utilizing the pharmaco-therapeutic advantage of the peritoneal barrier. Despite three large, randomized clinical trials comparing intravenous with intraperitoneal chemotherapy showing improved outcomes for those receiving at least part of their chemotherapy by the intraperitoneal route. Cisplatin has been the most active drug for the treatment of ovarian cancer for the last 4 decades and the prognosis for women with ovarian cancer can be defined by the tumor response to cisplatin. Those whose tumors are innately platinum-resistant at the time of initial treatment have a very poor prognosis. Although the majority of patients with ovarian cancer respond to front-line platinum combination chemotherapy the majority will develop disease that becomes resistant to cisplatin and will ultimately succumb to the disease. Improving the efficacy of cisplatin could have a major impact in the fight against this disease. Arsenite is an exciting agent that not only has inherent single-agent tumoricidal activity against ovarian cancer cell lines but also multiple biochemical interactions that may enhance the cytotoxicity of cisplatin including inhibition of deoxyribose nucleic acid (DNA repair. In vitro studies suggest that arsenite may enhance the activity of cisplatin in other cell types. Arsenic trioxide is already used clinically to treat acute promyelocytic leukemia demonstrating its safety profile. Further research in ovarian cancer is warranted to define

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

    Science.gov (United States)

    2016-10-18

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

  13. Municipal distribution of ovarian cancer mortality in Spain

    Directory of Open Access Journals (Sweden)

    Vidal Enrique

    2008-09-01

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

  14. 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.

  15. 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...

  16. Defining Therapy for Recurrent Platinum-sensitive Ovarian Cancer

    Science.gov (United States)

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

  17. 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...

  18. 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.

  19. Sulfated sugars in the extracellular matrix orchestrate ovarian cancer development: 'When sweet turns sour'

    NARCIS (Netherlands)

    Vallen, M.J.E.; Steen, S.C.H.A. van der; Tilborg, A.A. Van; Massuger, L.F.A.G.; Kuppevelt, T.H. van

    2014-01-01

    Considering the high mortality of ovarian cancer, novel approaches for diagnostics and therapy are urgently needed. Cancer initiation, progression, and invasion occur in a complex and dynamic microenvironment which depends on the interplay between host cell responses and tumor activity. Chondroitin

  20. Cytochrome P450 CYP1B1 over-expression in primary and metastatic ovarian cancer.

    Science.gov (United States)

    McFadyen, M C; Cruickshank, M E; Miller, I D; McLeod, H L; Melvin, W T; Haites, N E; Parkin, D; Murray, G I

    2001-07-20

    Ovarian cancer is the most frequent cause of death from gynaecological malignancies world wide. Little improvement has been made in the long-term outcome of this disease, with the 5-year survival of patients only 30%. This poor prognosis is due to the late presentation of the disease and to the unpredictable response of ovarian cancer to chemotherapy. The cytochrome P450 enzymes are a superfamily of haemoproteins, known to be involved in the metabolic activation and/or detoxification of a number of anti-cancer drugs. CYP1B1 is a tumour-related form of cytochrome P450 which is over expressed in a wide variety of primary tumours of different histological type. The presence of CYP1B1 may be of importance in the modulation of these tumours to anti-cancer drugs. We have conducted a comprehensive immunohistochemical investigation, into the presence of cytochrome P450 CYP1B1 in primary and metastatic ovarian cancer. The key findings of this study are the increased expression of CYP1B1 in the majority of ovarian cancers investigated (92%), with a strong correlation demonstrated between CYP1B1 expression in both primary and metastatic ovarian cancer (P = 0.005 Spearman's rank correlation test). In contrast no detectable CYP1B1 was found in normal ovary.

  1. A novel approach to breast cancer prevention: reducing excessive ovarian androgen production in elderly women.

    Science.gov (United States)

    Secreto, Giorgio; Sieri, Sabina; Agnoli, Claudia; Grioni, Sara; Muti, Paola; Zumoff, Barnett; Sant, Milena; Meneghini, Elisabetta; Krogh, Vittorio

    2016-08-01

    Minimizing endogenous estrogen production and activity in women at high risk for breast cancer is a prominent approach to prevention of the disease. A number of clinical trials have shown that the administration of selective-estrogen receptor modulators or aromatase inhibitors significantly reduces the incidence of breast cancer in healthy women. Unfortunately, these drugs often produce adverse effects on the quality of life and are, therefore, poorly accepted by many women, even those who are at high risk for breast cancer. We propose a novel alternative approach to decreasing estrogen production: suppression of ovarian synthesis of the androgen precursors of estrogens by administration of long-acting gonadotropin-releasing hormone analogs to women with ovarian stromal hyperplasia. The specific target population would be elderly postmenopausal women, at increased risk of breast cancer, and with high blood levels of testosterone, marker of ovarian hyperandrogenemia, and recognized factor of risk for breast cancer. Testosterone levels are measured at baseline to identify women at risk and during the follow-up to evaluate the effectiveness of therapy. The postmenopausal ovary is an important source of excessive androgen production which originates from the ovarian interstitial cell hyperplasia frequently present in breast cancer patients. We propose to counter the source of androgen excess in women with ovarian stromal hyperplasia, thus reducing the substrate for estrogen formation without completely inhibiting estrogen synthesis. Available evidence indicates that gonadotropin-releasing hormone analogs can be safely used for breast cancer prevention in postmenopausal women.

  2. Biological Basis for Chemoprevention of Ovarian Cancer. Addendum

    Science.gov (United States)

    2007-10-01

    those who use oral contraceptive pills for more than 5 years or have 3 children decrease their risk of ovarian cancer by greater than 50%. The...that the oral contraceptive has a potent apoptotic effect on the ovarian epithelium, mediated by the progestin component. In addition, in subsequent...calendar method. In addition, information on oral contraceptives and hormone replacement therapy is obtained. Data on the family history of cancer

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

    Science.gov (United States)

    2015-10-01

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

  4. Gambogic acid sensitizes ovarian cancer cells to doxorubicin through ROS-mediated apoptosis.

    Science.gov (United States)

    Wang, Jianxia; Yuan, Zhixiang

    2013-09-01

    Ovarian cancer is one human malignancy which has response portly to doxorubicin. The anti-cancer activity of gambogic acid has been tested in in vitro and in vivo studies. In this study, we showed that gambogic acid, a natural compound, could potentiate the anticancer activity of doxorubicin in ovarian cancer through ROS-mediated apoptosis. Platinum-resistant human ovarian cancer cell line (SKOV-3) was treated with gambogic acid, doxorubicin, or the combination of both to investigate cell proliferation and apoptosis. We found that the combination of gambogic acid and doxorubicin causes synergistic loss of cell viability in SKOV-3 cells and this synergistic effect correlated with increased cellular ROS accumulation. Moreover, in vivo results showed that gambogic acid and doxorubicin combination resulted in a synergistic suppressing effect on tumor growth in ovarian cancer mice model. Taken together, the results suggested that doxorubicin in combination with gambogic acid might provide a promising therapeutic strategy to enhance chemosensitivity of ovarian cancer to doxorubicin.

  5. Resveratrol, Acetyl-Resveratrol, and Polydatin Exhibit Antigrowth Activity against 3D Cell Aggregates of the SKOV-3 and OVCAR-8 Ovarian Cancer Cell Lines

    OpenAIRE

    Hogg, Simon J.; Kenny Chitcholtan; Wafaa Hassan; Peter H. Sykes; Ashley Garrill

    2015-01-01

    Resveratrol has aroused significant scientific interest as it has been claimed that it exhibits a spectrum of health benefits. These include effects as an anti-inflammatory and an antitumour compound. The purpose of this study was to investigate and compare any potential antigrowth effects of resveratrol and two of its derivatives, acetyl-resveratrol and polydatin, on 3D cell aggregates of the EGFR/Her-2 positive and negative ovarian cancer cell lines SKOV-3 and OVCAR-8, respectively. Results...

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    1998-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

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

  9. Ovarian cancer: a molecularly insidious disease.

    Science.gov (United States)

    Mezzanzanica, Delia

    2015-01-01

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

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

    Science.gov (United States)

    Moss, Charlotte; Kaye, Stan B

    2002-09-01

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

  11. 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.

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

    Science.gov (United States)

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

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

    Science.gov (United States)

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

    2012-04-01

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

  14. Obesity and survival among women with ovarian cancer

    DEFF Research Database (Denmark)

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

    2015-01-01

    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......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...... 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...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1997-03-01

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

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

    Science.gov (United States)

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

  17. SiRNA and epigenetic aberrations in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Hamed Mirzaei

    2016-01-01

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

  18. 77 FR 41791 - Proposed Collection; Comment Request; Prostate, Lung, Colorectal and Ovarian Cancer Screening...

    Science.gov (United States)

    2012-07-16

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

  19. Adaptation of ovarian cancer cells to the peritoneal environment: Multiple mechanisms of the developmental patterning gene HOXA9

    Science.gov (United States)

    Ko, Song Yi; Naora, Honami

    2015-01-01

    The lethality of ovarian cancer stems from its propensity to involve the peritoneal cavity. However, the mechanisms that enable ovarian cancer cells to readily adapt to the peritoneal environment are not well understood. Here, we describe our recent studies in which we identified the mechanisms by which the transcription factor encoded by the patterning gene HOXA9 promotes the aggressive behavior of ovarian cancer. Firstly, we identified that HOXA9 promotes ovarian tumor growth and angiogenesis by activating the gene encoding transforming growth factor-β2 (TGF-β2), which in turn stimulates peritoneal fibroblasts and mesenchymal stem cells to acquire features of cancer-associated fibroblasts. Secondly, by inducing TGF-β2 and chemokine (C-C motif) ligand 2, HOXA9 stimulates peritoneal macrophages to acquire an immunosuppressive phenotype. Thirdly, HOXA9 stimulates attachment of ovarian cancer cells to peritoneal mesothelial cells by inducing expression of P-cadherin. By inducing P-cadherin, HOXA9 also enables floating cancer cells in the peritoneal cavity to form aggregates and escape anoikis. Together, our studies demonstrate that HOXA9 enables ovarian cancer cells to adapt to the peritoneal environment and ‘educates’ different types of stromal cells to become permissive for tumor growth. Our studies provide new insights into the regulation of tumor-stroma interactions in ovarian cancer and implicate several key effector molecules as candidate therapeutic targets. PMID:26000332

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

    Science.gov (United States)

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

    2016-08-01

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

  1. The Wilms' Tumor Gene WT1 −17AA/−KTS Splice Variant Increases Tumorigenic Activity Through Up-Regulation of Vascular Endothelial Growth Factor in an In Vivo Ovarian Cancer Model

    Directory of Open Access Journals (Sweden)

    Keiko Yamanouchi

    2014-10-01

    Full Text Available The Wilms' tumor 1 gene WT1 encodes a zinc transcription factor involved in a variety of cancer-related processes. In this study, we sought to investigate the effects of WT1 splice variants on tumorigenic activity and survival in an in vivo ovarian cancer model. To this end, we established stable ovarian cancer cell lines transduced with lentiviral constructs containing each of the four WT1 splice variants (−17AA/−KTS, +17AA/−KTS, −17AA/+KTS, and +17AA/+KTS. In mice inoculated intraperitoneally with SKOV3ip1 cells expressing WT1 −17AA/−KTS, disseminated tumor weights and production of ascites were significantly increased compared with those in mice inoculated with cells expressing the control vector. The overall survival in mice inoulated with WT1 −17AA/−KTS-expressing cells was significantly shorter than that in mice inoculated with control cells (P = .0115. Immunoblot analysis revealed that WT1 −17AA/−KTS significantly increased the expression of vascular endothelial growth factor (VEGF compared with the control. Greater numbers of CD31-immunopositive vessels were observed in tumors from mice injected with cells expressing WT1 −17AA/−KTS than in tumors from control mice. Finally, WT1 −17AA/−KTS significantly increased tumor microvessel density compared with that in the control (P < .05. Treatment with anti-VEGF antibody (bevacizumab inhibited tumor growth, dissemination, and ascites production in mice injected with cells expressing WT1 −17AA/−KTS. The overexpression of WT1 −17AA/−KTS induced a more aggressive phenotype in ovarian cancer cells through VEGF up-regulation in an in vivo ovarian cancer model. Our findings indicated that WT1 −17AA/−KTS enhanced tumorigenic activity and could decreased patient survival through up-regulation of VEGF expression in ovarian cancers.

  2. Serous ovarian, fallopian tube and primary peritoneal cancers

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  3. Research Perspective: Potential Role of Nitazoxanide in Ovarian Cancer Treatment. Old Drug, New Purpose?

    Energy Technology Data Exchange (ETDEWEB)

    Di Santo, Nicola, E-mail: nico.disanto@duke.edu; Ehrisman, Jessie [Division of Gynecologic Oncology, Duke University Medical Center, Durham, NC 27710 (United States)

    2013-09-10

    Among gynecological malignancies epithelial ovarian cancer (EOC) is the leading cause of death. Despite improvements in conventional chemotherapy combinations, the overall cure rate has remained mostly stable over the years, and only 10%–15% of patients maintain a complete response following first-line therapy. To improve the efficacy of ovarian cancer chemotherapy it is essential to develop drugs with new mechanisms of action. Compared to normal tissues, protein disulfide isomerase (PDI) is overexpressed in ovarian tumors. PDI is a cellular enzyme in the lumen of the endoplasmic reticulum (ER) of eukaryotes or the periplasmic region of prokaryotes. This protein catalyzes the formation and breakage of disulphide bonds between cysteine residues in proteins, which affects protein folding. Selective inhibition of PDI activity has been exhibited both in vitro and in vivo anticancer activity in human ovarian cancer models. PDI inhibition caused accumulation of unfolded or misfolded proteins, which led to ER stress and the unfolded protein response (UPR), and in turn resulted in cell death. Nitazoxanide [NTZ: 2-acetyloxy-N-(5-nitro-2-thiazolyl)benzamide] is a thiazolide antiparasitic agent with excellent activity against a wide variety of protozoa and helminths. In this article, we propose that NTZ, acting as PDI inhibitor, may be a new and potent addition to the chemotherapeutic strategy against ovarian cancer.

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

    Science.gov (United States)

    2017-01-31

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

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

    Science.gov (United States)

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

    2012-08-01

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

  6. Increased Expression of the Pro-Protein Convertase Furin Predicts Decreased Survival in Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Robert E. Page

    2007-01-01

    Full Text Available Background: Proprotein convertases (PCs are serine proteases that after restricted proteolysis activate many proteins that play a crucial role in cancer such as metalloproteinases, growth factors and growth factor receptors, adhesion molecules, and angiogenic factors. Although the expression of several PCs is increased in many tumors, their expression in primary ovarian tumors has not been studied in detail. We sought to determine if there was an association between the expression of the ubiquitously expressed PCs, furin, PACE-4, PC-5 and PC-7, and ovarian tumor progression. Methods: We assessed their expression by RT-PCR, Real-time PCR, Western blot, and immunohistochemistry using cells derived from normal human ovarian surface epithelium (HOSE and cancer cell lines as well as ovarian epithelial cancer specimens (45 RT-PCR/Real-time PCR, and 120 archival specimens for Immunohistochemistry. Results: We found that furin expression was restricted to the cancer cell lines. In contrast, PACE-4 and PC-7 showed expression only in normal HOSE cells lines. Furthermore, furin was predominantly expressed in primary tumors from patients who survived for less than five years. The other PCs are either expressed in the group of survivors (PC-7 and PACE4 or expressed in low amounts (PC-5. Conclusions: Our studies point to a clear relationship between furin and ovarian cancer. In addition, these results show that furin exhibits the closest association with ovarian cancer among the ubiquitously expressed PCs, arguing against the redundancy of these proteases. In summary, furin may constitute a marker for ovarian tumor progression and could contribute to predict the outcome of this disease.

  7. Noxa enhances the cytotoxic effect of gemcitabine in human ovarian cancer cells.

    Science.gov (United States)

    Cao, Kang; Yang, Jing; Lin, Chao; Wang, Bao-ning; Yang, Yuan; Zhang, Jing; Dai, Jun; Li, Lei; Nie, Chun-lai; Yuan, Zhu; Li, Ming-yuan

    2012-05-01

    Noxa is an important proapoptotic protein in the intrinsic pathway of cell apoptosis. Experiments were carried out to investigate whether Noxa could, therefore, enhance the cytotoxic effect of gemcitabine in human ovarian cancer cell lines (A2780 and COC1). In this study, the combined treatment of Noxa and gemcitabine, in vitro, significantly inhibited the proliferation of A2780 and COC1 cells, as verified by MTT assay, Hoechst staining, and flow cytometric analysis. Moreover, the combination of Noxa and gemcitabine inhibited tumor growth and prolonged the survival of nude mice in vivo. The combined treatment also inhibited the growth of tumor xenografts through the inhibition of proliferation and the induction of apoptosis, as observed in immunohistochemical anti-PCNA staining and TdT-mediated dUTP-biotin nick-end labeling (TUNEL) assay. Our data suggest that Noxa exhibited potent proapoptotic activity against human ovarian cancer cells, and the combination of Noxa and gemcitabine showed a more significant cytotoxic effect against ovarian cancer cells in comparison with either of these agents alone. To our knowledge, we have provided the first evidence that Noxa can enhance therapeutic responses of ovarian cancer cells to gemcitabine, and that it could be potentially useful as a chemosensitizer in ovarian cancer therapy.

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

    OpenAIRE

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

    2016-01-01

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

  9. 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...

  10. Ovarian cancer plasticity and epigenomics in the acquisition of a stem-like phenotype

    Directory of Open Access Journals (Sweden)

    Berry Nicholas B

    2008-11-01

    Full Text Available Abstract Aggressive epithelial ovarian cancer (EOC is genetically and epigenetically distinct from normal ovarian surface epithelial cells (OSE and early neoplasia. Co-expression of epithelial and mesenchymal markers in EOC suggests an involvement of epithelial-mesenchymal transition (EMT in cancer initiation and progression. This phenomenon is often associated with acquisition of a stem cell-like phenotype and chemoresistance that correlate with the specific gene expression patterns accompanying transformation, revealing a plasticity of the ovarian cancer cell genome during disease progression. Differential gene expressions between normal and transformed cells reflect the varying mechanisms of regulation including genetic changes like rearrangements within the genome, as well as epigenetic changes such as global genomic hypomethylation with localized promoter CpG island hypermethylation. The similarity of gene expression between ovarian cancer cells and the stem-like ovarian cancer initiating cells (OCIC are surprisingly also correlated with epigenetic mechanisms of gene regulation in normal stem cells. Both normal and cancer stem cells maintain genetic flexibility by co-placement of activating and/or repressive epigenetic modifications on histone H3. The co-occupancy of such opposing histone marks is believed to maintain gene flexibility and such bivalent histones have been described as being poised for transcriptional activation or epigenetic silencing. The involvement of both-microRNA (miRNA mediated epigenetic regulation, as well as epigenetic-induced changes in miRNA expression further highlight an additional complexity in cancer stem cell epigenomics. Recent advances in array-based whole-genome/epigenome analyses will continue to further unravel the genomes and epigenomes of cancer and cancer stem cells. In order to illuminate phenotypic signatures that delineate ovarian cancer from their associated cancer stem cells, a priority must lie

  11. Chlamydia Peritonitis and Ascites Mimicking Ovarian Cancer

    Science.gov (United States)

    Macer, Matthew; Azodi, Masoud

    2016-01-01

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

  12. Isolated Axillary Lymph Node Metastasis from Serous Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Hemant Goyal

    2012-01-01

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

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  14. 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....

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    BACKGROUND: In vitro and observational epidemiological studies suggest that vitamin D may play a role in cancer prevention. However, the relationship between vitamin D and ovarian cancer is uncertain, with observational studies generating conflicting findings. A potential limitation...... of 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...... employed SNPs with well-established associations with 25(OH)D concentration as instrumental variables for MR: rs7944926 (DHCR7), rs12794714 (CYP2R1) and rs2282679 (GC). We included 31 719 women of European ancestry (10 065 cases, 21 654 controls) from the Ovarian Cancer Association Consortium, who were...

  16. Role of prevention and screening in epithelial ovarian cancer

    Directory of Open Access Journals (Sweden)

    Peddireddi Reddi Rani

    2015-08-01

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

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

    Science.gov (United States)

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

    2015-11-01

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

  18. Noscapine sensitizes chemoresistant ovarian cancer cells to cisplatin through inhibition of HIF-1α.

    Science.gov (United States)

    Su, Wenjing; Huang, Lei; Ao, Qilin; Zhang, Qinghua; Tian, Xun; Fang, Yong; Lu, Yunping

    2011-06-01

    Hypoxia-inducible factor 1 alpha (HIF-1α) is closely related with chemoresistance of solid tumors. The purpose of this study was to investigate the ability of noscapine to inhibit HIF-1α and sensitize ovarian cancer cells to cisplatin (DDP) under hypoxic conditions. Herein, we report that noscapine sensitized cobalt-induced chemoresistant ovarian cancer cells to DDP-induced apoptosis and inhibition of cell proliferation. Noscapine also promoted proteasome-mediated degradation of cobalt-stabilized HIF-1α protein, with subsequent inhibition of HIF-1 transcriptional activity. These data establish noscapine as a small molecule inhibitor of HIF-1α and provide an evidence for its combination with DDP in combating ovarian cancer chemoresistance.

  19. Serum tumour marker CA 125 in monitoring of ovarian cancer during first-line chemotherapy

    DEFF Research Database (Denmark)

    Tuxen, M K; Sölétormos, G; Dombernowsky, P

    2001-01-01

    of this study was to assess the ability of CA 125 to monitor patients with ovarian cancer during postoperative chemotherapy. 255 patients with stage IC-IV ovarian cancer were allocated to the tumour marker monitoring study. The evaluation of CA 125 information was based on the analytical imprecision, the normal...... for identifying progression and non-progression during first-line chemotherapy was 91.9%. The median lead time for true positive results was 41 days. Using the new elaborated criterion the efficiency of CA 125 for identifying progression and non-progression during first-line chemotherapy was 90.5%. The median...... lead time for true positive results was 35 days. CA 125 gave reliable prediction of progressive disease during postoperative chemotherapy. The results indicate a high applicability of the presented progression criteria during CA 125 monitoring of patients with changing activity of ovarian cancer....

  20. An endogenous aryl hydrocarbon receptor ligand inhibits proliferation and migration of human ovarian cancer cells.

    Science.gov (United States)

    Wang, Kai; Li, Yan; Jiang, Yi-Zhou; Dai, Cai-Feng; Patankar, Manish S; Song, Jia-Sheng; Zheng, Jing

    2013-10-28

    The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor mediates many biological processes. Herein, we investigated if 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE, an endogenous AhR ligand) regulated proliferation and migration of human ovarian cancer cells via AhR. We found that AhR was widely present in many histotypes of ovarian cancer tissues. ITE suppressed OVCAR-3 cell proliferation and SKOV-3 cell migration in vitro, which were blocked by AhR knockdown. ITE also suppressed OVCAR-3 cell growth in mice. These data suggest that the ITE might potentially be used for therapeutic intervention for at least a subset of human ovarian cancer.

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

    Science.gov (United States)

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

    2009-11-28

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

  2. The relationship of haplotype in lactotransferrin and its expression levels in Chinese Han ovarian cancer

    Institute of Scientific and Technical Information of China (English)

    Lanqin Cao; Yanhong Zhou; Xin Li; Hong Yi

    2011-01-01

    Chromosomal DNA sequence polymorphisms may contribute to individuality,confer risk for diseases,and most commonly are used as genetic markers in association study.The iron-binding protein lactoferrin inhibits bacterial growth by sequestering essential iron and also exhibits antitumor,anti-inflammatory,and immunoregulatory activities.The gene coding for lactotransferrin (LTF) is polymorphic,with the occurrence of several common alleles in the general population.This genetically determined variation can affect LTF functions.In this study,we determined the distribution of LTF gene polymorphisms (rs1126477,rs1126478,rs2073495,and rs9110) in the Chinese Han population and investigated whether these polymorphisms were associated with increased risk of ovarian carcinoma in the Chinese.It was found that the rs1126477 was correlated significantly with ovarian cancer.The frequency of A allele of rs1126477 was significantly higher in 700 ovarian cancer patients compared with that in the control group of 700 cases (P < 0.01,x2=6.79).The frequency of AA genotype was significantly higher in ovarian cancer patients compared with that in the control group (P < 0.05,x2=6.49).AA genotype is the risk factor of ovarian cancer.The odds ratio (OR) was 2.24 and the 95% confidence interval (CI) was 1.08-4.59,respectively.The ‘A-G-C-C' haplotype constructed with rs1126477,rs1126478,rs2073495,and rs9110 was the risk factor to be ovarian cancer.The expression of LTF gene was lower in individuals with ‘A-G-C-C' haplotype compared with that in individuals without ‘A-G-C-C' haplotype.These findings suggested that rs1126477 could play important roles in ovarian carcinoma physiological processes in the Chinese.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  4. Study examines outcomes from surgery to prevent ovarian cancer

    Science.gov (United States)

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

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

    Science.gov (United States)

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

    1982-10-21

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

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

    Directory of Open Access Journals (Sweden)

    Angela Toss

    2015-01-01

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

  7. 76 FR 22108 - Proposed Collection; Comment Request; Prostate, Lung, Colorectal and Ovarian Cancer Screening...

    Science.gov (United States)

    2011-04-20

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

  8. Cytochrome P450 CYP1B1 over-expression in primary and metastatic ovarian cancer

    OpenAIRE

    McFadyen, M C E; Cruickshank, M E; Miller, I D; McLeod, H L; Melvin, W T; N. E. Haites; Parkin, D.; Murray, G. I.

    2001-01-01

    Ovarian cancer is the most frequent cause of death from gynaecological malignancies world wide. Little improvement has been made in the long-term outcome of this disease, with the 5-year survival of patients only 30%. This poor prognosis is due to the late presentation of the disease and to the unpredictable response of ovarian cancer to chemotherapy. The cytochrome P450 enzymes are a superfamily of haemoproteins, known to be involved in the metabolic activation and/or detoxification of a num...

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

    Science.gov (United States)

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

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

    Directory of Open Access Journals (Sweden)

    Maria Szubert

    2016-07-01

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

  11. NFATC1 promotes cell growth and tumorigenesis in ovarian cancer up-regulating c-Myc through ERK1/2/p38 MAPK signal pathway.

    Science.gov (United States)

    Xu, Wenwen; Gu, Junjie; Ren, Qingling; Shi, Yanqiu; Xia, Qinhua; Wang, Jing; Wang, Suli; Wang, Yingchun; Wang, Jinhua

    2016-04-01

    It has been reported that nuclear factor of activated T cells (NFATC1) was up-regulated in cancers mediating malignant behaviors. However, the role of NFATC1 in ovarian cancer has not been elucidated. In the present study, we undertook to explore the clinicopathological significance of NFATC1 expression and the mechanism by which NFATC1 works in ovarian cancer. Expression status of NFATC1 was examined using immunohistochemistry. Both knockdown and re-expression of NFATC1 on ovarian cancer cells were employed to observe the effect overgrowth. It was found that NFATC1 was significantly overexpressed in ovarian cancer tissues in comparison with paired normal control tissues and that overexpression of NFATC1 was significantly associated with metastasis and poor prognosis on clinical tissue level. In in vitro ovarian cancer cell lines, we found that NFATC1 can promote proliferation up-regulating c-myc through activation of ERK1/2/p38/MAPK signal pathway. Together, the results we obtained demonstrated that NFATC1 played oncogenic role in ovarian cancer. Mechanistically, NFATC1 promoted growth of ovarian cancer cells up-regulating c-myc through activation of ERK1/2/p38/MAPK signal pathway, suggesting that NFATC1 might be used as a therapeutic target for ovarian cancer.

  12. Symptom interpretation and health care seeking in ovarian cancer

    DEFF Research Database (Denmark)

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

    2011-01-01

    with ovarian cancer. These results were combined with findings from semi-structured qualitative research interviews on women's bodily experiences with symptom development. RESULTS: A number of 663 Danish women with ovarian cancer attended 27 different kinds of primary health care providers in a total of 14......BACKGROUND: Ovarian cancer is the leading cause of death among women suffering from gynaecological malignancies in the Western world. Worldwide, approximately 200,000 women are diagnosed with the disease each year. This article deals with the health care seeking and symptom interpretation process...... among Danish women, who have a very high mortality rate. METHODS: The health seeking and symptom interpretation process was analysed via combining study methods. The material consisted of registry data dealing with the use of public health care and hospital services of Danish women, newly diagnosed...

  13. Bacillus intermedius ribonuclease (BINASE) induces apoptosis in human ovarian cancer cells.

    Science.gov (United States)

    Garipov, Azat R; Nesmelov, Alexander A; Cabrera-Fuentes, Hector A; Ilinskaya, Olga N

    2014-12-15

    The cytotoxic effects of Bacillus intermedius RNase (binase) towards ovarian cancer cells (SKOV3 and OVCAR5) were studied in comparison to normal ovarian epithelial cells (HOSE1 and HOSE2). Binase decreased viability and induced the selective apoptosis of ovarian cancer cells. The apoptosis rate was 50% in SKOV3 and 48% in OVCAR5 cells after 24 h of binase treatment (50 μg/ml). Binase-induced apoptosis in these cell lines was accompanied by caspase-3 activation and poly(ADP-ribose) polymerase fragmentation. Normal ovarian epithelial cells were not affected by binase, except for a slight decrease of HOSE2 cell viability and the appearance of traces of activated caspase-3, but not the poly(ADP-ribose) polymerase 85-kDA fragment. Binase did not induce alteration of EZH2 (enhancer of zeste-homolog-2) protein expression neither, in tumor nor in normal cells. In conclusion, selective binase-induced cell death and apoptosis via poly(ADP-ribose) polymerase fragmentation may serve as a new treatment option against ovarian cancer progression.

  14. Salinomycin reduces stemness and induces apoptosis on human ovarian cancer stem cell

    Science.gov (United States)

    Lee, Hyun-Gyo; Shin, So-Jin; Cha, Soon-Do

    2017-01-01

    Objective Cancer stem cells (CSCs) represent a subpopulation of undifferentiated tumorigenic cells thought to be responsible for tumor initiation, maintenance, drug resistance, and metastasis. The role of CSCs in drug resistance and relapse of cancers could significantly affect outcomes of ovarian cancer patient. Therefore, therapies that target CSCs could be a promising approach for ovarian cancer treatment. The antibiotic salinomycin has recently been shown to deplete CSCs. In this study, we evaluated the effect of salinomycin on ovarian cancer stem cells (OCSCs), both alone and in combination with paclitaxel (PTX). Methods The CD44+CD117+CSCs were obtained from the ascitic fluid of patients with epithelial ovarian cancer by using an immune magnetic-activated cell sorting system. OCSCs were treated with PTX and salinomycin either singly or in combination. Cell viability and apoptosis assays were performed and spheroid-forming ability was measured. The expression of sex determining region Y-box 2 (SOX2) and octamer-binding transcription factor 3/4 (OCT3/4) mRNA was determined using reverse transcription polymerase chain reaction, and protein expression was observed using western blot analysis. Results Treatment with salinomycin alone reduced the stemness marker expression and spheroid-forming ability of OCSCs. Treatment with PTX alone did not decrease the viability of OCSCs. Treatment with a combination of salinomycin decreased the viability of OCSCs and promoted cell apoptosis. The enhancement of combination treatment was achieved through the apoptosis as determined by annexin V/propidium iodide (PI) staining, caspase-3 activity, and DNA fragmentation assay. Conclusion Based on our findings, combining salinomycin with other anti-cancer therapeutic agents holds promise as an ovarian cancer treatment approach that can target OCSCs. PMID:27894167

  15. ROS accumulation by PEITC selectively kills ovarian cancer cells via UPR-mediated apoptosis

    Directory of Open Access Journals (Sweden)

    Yoon-hee eHong

    2015-07-01

    Full Text Available Unfolded protein response (UPR is crucial for both survival and death of mammalian cells, which is regulated by reactive oxygen species (ROS and nutrient depletion. In this study, we demonstrated the effect of ROS-accumulation, induced by β-phenethyl isothiocyanate (PEITC, on UPR mediated apoptosis in ovarian cancer cells. We used ovarian cancer cell lines, PA-1 and SKOV-3, with different p53 status (wild- and null- type, respectively. PEITC caused increased ROS-accumulation and inhibited proliferation selectively in ovarian cancer cells, and glutathione (GSH depletion in SKOV-3. However, PEITC did not cause any effect in normal ovarian epithelial cells and peripheral blood mononuclear cells. After 48 h of PEITC treatment (5 µM, apoptotic cell death was shown to increase significantly in the ovarian cancer cells and not in the normal cells. The key regulator of UPR-mediated apoptosis, CHOP/GADD153 and ER resident chaperone BiP/GRP78 were parallely up-regulated with activation of two major sensors of the UPR (PERK and ATF-6 in PA-1; PERK, and IRE1α in SKOV-3 in response to ROS accumulation induced by PEITC (5 µM. ROS scavenger, N-acetyl-cysteine (NAC, attenuated the effect of PEITC on UPR signatures (P-PERK, IRE1α, CHOP/GADD153, and BiP/GRP78, suggesting the involvement of ROS in UPR-mediated apoptosis. Altogether, PEITC induces UPR-mediated apoptosis in ovarian cancer cells via accumulation of ROS in a cancer-specific manner.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-09-10

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

  17. Proteomic biomarkers for overall and progression-free survival in ovarian cancer patients

    DEFF Research Database (Denmark)

    Høgdall, Estrid; Fung, Eric T; Christensen, Ib Jarle;

    2010-01-01

    To determine if the level of apolipoprotein A1, hepcidin, transferrin, inter-α trypsin IV internal fragment, transthyretin (TT), connective-tissue activating protein 3 (CTAP3), serum amyloid A1, β-2 microglobulin (B2M) might have impact on overall and progression-free survival for ovarian cancer ...

  18. Proteomic biomarkers for overall and progression-free survival in ovarian cancer patients

    DEFF Research Database (Denmark)

    Høgdall, Estrid; Fung, Eric T; Christensen, Ib Jarle;

    2010-01-01

    To determine if the level of apolipoprotein A1, hepcidin, transferrin, inter-a trypsin IV internal fragment, transthyretin (TT), connective-tissue activating protein 3 (CTAP3), serum amyloid A1, ß-2 microglobulin (B2M) might have impact on overall and progression-free survival for ovarian cancer ...

  19. A novel proteomic biomarker panel as a diagnostic tool for patients with ovarian cancer

    DEFF Research Database (Denmark)

    Høgdall, Claus; Fung, Eric T; Christensen, Ib J;

    2011-01-01

    Previous reports have shown that the proteomic markers apolipoprotein A1, hepcidin, transferrin, inter-alpha trypsin IV internal fragment, transthyretin, connective-tissue activating protein 3 and beta-2 microglobulin may discriminate between a benign pelvic mass and ovarian cancer (OC). The aim ...

  20. Limited independent prognostic value of MMP-14 and MMP-2 expression in ovarian cancer

    NARCIS (Netherlands)

    Vos, M.C.; Wurff, A.A. van der; Bulten, J.; Kruitwagen, R.; Feijen, H.; Kuppevelt, T.H. van; Hendriks, T.; Massuger, L.F.

    2016-01-01

    BACKGROUND: In cancer, various MMPs play a role in progression and metastasis and their overexpression generally indicates a poor prognosis. MMP-14 is the main activator of MMP-2 and both molecules play a role in normal ovarian follicular development. Earlier reports indicated a prognostic value for

  1. Chemokine Receptors in Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Goda G. Muralidhar

    2013-12-01

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

  2. Diagnosis and Management of Peritoneal Metastases from Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Evgenia Halkia

    2012-01-01

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

  3. 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.

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

    OpenAIRE

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

    2015-01-01

    Ovarian cancer is the most important cause of gynecological cancer-related mortality, with the majority of women presenting with advanced disease. Although surgery and chemotherapy can improve survival rates, it is necessary to integrate alternative strategies to improve the outcomes. Advances in understanding the role of immune system in the pathogenesis of cancer have led to the rapid evolvement of immunotherapy, which might establish a sustained immune system response against recurring can...

  5. Decitabine reactivated pathways in platinum resistant ovarian cancer.

    Science.gov (United States)

    Fang, Fang; Zuo, Qingyao; Pilrose, Jay; Wang, Yinu; Shen, Changyu; Li, Meng; Wulfridge, Phillip; Matei, Daniela; Nephew, Kenneth P

    2014-06-15

    Combination therapy with decitabine, a DNMTi and carboplatin resensitized chemoresistant ovarian cancer (OC) to platinum inducing promising clinical activity. We investigated gene-expression profiles in tumor biopsies to identify decitabine-reactivated pathways associated with clinical response. Gene-expression profiling was performed using RNA from paired tumor biopsies before and 8 days after decitabine from 17 patients with platinum resistant OC. Bioinformatic analysis included unsupervised hierarchical-clustering, pathway and GSEA distinguishing profiles of "responders" (progression-free survival, PFS>6 months) and "non-responders" (PFSdecitabine (TGF-β and Hh). Gene-expression profiling identified specific pathways altered by decitabine and associated with platinum-resensitization and clinical benefit in OC. Our data could influence patient stratification for future studies using epigenetic therapies.

  6. Identification of the NAC1-regulated genes in ovarian cancer.

    Science.gov (United States)

    Gao, Min; Wu, Ren-Chin; Herlinger, Alice L; Yap, Kailee; Kim, Jung-Won; Wang, Tian-Li; Shih, Ie-Ming

    2014-01-01

    Nucleus accumbens-associated protein 1 (NAC1), encoded by the NACC1 gene, is a transcription co-regulator that plays a multifaceted role in promoting tumorigenesis. However, the NAC1-regulated transcriptome has not been comprehensively defined. In this study, we compared the global gene expression profiles of NAC1-overexpressing SKOV3 ovarian cancer cells and NAC1-knockdown SKOV3 cells. We found that NAC1 knockdown was associated with up-regulation of apoptotic genes and down-regulation of genes involved in cell movement, proliferation, Notch signaling, and epithelial-mesenchymal transition. Among NAC1-regulated genes, FOXQ1 was further characterized because it is involved in cell motility and epithelial-mesenchymal transition. NAC1 knockdown decreased FOXQ1 expression and promoter activity. Similarly, inactivation of NAC1 by expression of a dominant-negative construct of NAC1 suppressed FOXQ1 expression. Ectopic expression of NAC1 in NACC1 null cells induced FOXQ1 expression. NAC1 knockdown resulted in decreased cell motility and invasion, whereas constitutive expression of FOXQ1 rescued motility in cells after NAC1 silencing. Moreover, in silico analysis revealed a significant co-up-regulation of NAC1 and FOXQ1 in ovarian carcinoma tissues. On the basis of transcription profiling, we report a group of NAC1-regulated genes that may participate in multiple cancer-related pathways. We further demonstrate that NAC1 is essential and sufficient for activation of FOXQ1 transcription and that the role of NAC1 in cell motility is mediated, at least in part, by FOXQ1.

  7. 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

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

    DEFF Research Database (Denmark)

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

    2009-01-01

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

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

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

    Science.gov (United States)

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

    2016-07-13

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

  11. 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.

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

    Directory of Open Access Journals (Sweden)

    Liu Jinsong

    2005-02-01

    Full Text Available Abstract Background Insulin-like growth factor binding protein 2 (IGFBP2 is overexpressed in ovarian malignant tissues and in the serum and cystic fluid of ovarian cancer patients, suggesting an important role of IGFBP2 in the biology of ovarian cancer. The purpose of this study was to assess the role of increased IGFBP2 in ovarian cancer cells. Results Using western blotting and tissue microarray analyses, we showed that IGFBP2 was frequently overexpressed in ovarian carcinomas compared with normal ovarian tissues. Furthermore, IGFBP2 was significantly overexpressed in invasive serous ovarian carcinomas compared with borderline serous ovarian tumors. To test whether increased IGFBP2 contributes to the highly invasive nature of ovarian cancer cells, we generated IGFBP2-overexpressing cells from an SKOV3 ovarian cancer cell line, which has a very low level of endogenous IGFBP2. A Matrigel invasion assay showed that these IGFBP2-overexpressing cells were more invasive than the control cells. We then designed small interference RNA (siRNA molecules that attenuated IGFBP2 expression in PA-1 ovarian cancer cells, which have a high level of endogenous IGFBP2. The Matrigel invasion assay showed that the attenuation of IGFBP2 expression indeed decreased the invasiveness of PA-1 cells. Conclusions We therefore showed that IGFBP2 enhances the invasion capacity of ovarian cancer cells. Blockage of IGFBP2 may thus constitute a viable strategy for targeted cancer therapy.

  13. Chemotherapy Toxicity On Quality of Life in Older Patients With Stage I, Stage II, Stage III, or Stage IV Ovarian Epithelial, Primary Peritoneal Cavity, or Fallopian Tube Cancer

    Science.gov (United States)

    2016-02-09

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-05-02

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

  15. Apoptotic effects of salinomycin on human ovarian cancer cell line (OVCAR-3).

    Science.gov (United States)

    Kaplan, Fuat; Teksen, Fulya

    2016-03-01

    In this study, we studied the apoptotic and cytotoxic effects of salinomycin on human ovarian cancer cell line (OVCAR-3) as salinomycin is known as a selectively cancer stem cell killer agent. We used immortal human ovarian epithelial cell line (IHOEC) as control group. Ovarian cancer cells and ovarian epithelial cells were treated by different concentrations of salinomycin such as 0.1, 1, and 40 μM and incubated for 24, 48, and 72 h. Dimethylthiazol (MTT) cell viability assay was performed to determine cell viability and toxicity. On the other hand, the expression levels of some of the apoptosis-related genes, namely anti-apoptotic Bcl-2, apoptotic Bax, and Caspase-3 were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Additionally, Caspase-3 protein level was also determined. As a result, we concluded that incubation of human OVCAR-3 by 0.1 μM concentration of salinomycin for 24 h killed 40 % of the cancer cells by activating apoptosis but had no effect on normal cells. The apoptotic Bax gene expression was upregulated but anti-apoptotic Bcl-2 gene expression was downregulated. Active Caspase-3 protein level was increased significantly (p < 0.05).

  16. Lovastatin induces apoptosis of ovarian cancer cells and synergizes with doxorubicin: potential therapeutic relevance

    Directory of Open Access Journals (Sweden)

    Goard Carolyn A

    2010-03-01

    Full Text Available Abstract Background Ovarian carcinoma is a rarely curable disease, for which new treatment options are required. As agents that block HMG-CoA reductase and the mevalonate pathway, the statin family of drugs are used in the treatment of hypercholesterolemia and have been shown to trigger apoptosis in a tumor-specific manner. Recent clinical trials show that the addition of statins to traditional chemotherapeutic strategies can increase efficacy of targeting statin-sensitive tumors. Our goal was to assess statin-induced apoptosis of ovarian cancer cells, either alone or in combination with chemotherapeutics, and then determine these mechanisms of action. Methods The effect of lovastatin on ovarian cancer cell lines was evaluated alone and in combination with cisplatin and doxorubicin using several assays (MTT, TUNEL, fixed PI, PARP cleavage and synergy determined by evaluating the combination index. The mechanisms of action were evaluated using functional, molecular, and pharmacologic approaches. Results We demonstrate that lovastatin induces apoptosis of ovarian cancer cells in a p53-independent manner and synergizes with doxorubicin, a chemotherapeutic agent used to treat recurrent cases of ovarian cancer. Lovastatin drives ovarian tumor cell death by two mechanisms: first, by blocking HMG-CoA reductase activity, and second, by sensitizing multi-drug resistant cells to doxorubicin by a novel mevalonate-independent mechanism. This inhibition of drug transport, likely through inhibition of P-glycoprotein, potentiates both DNA damage and tumor cell apoptosis. Conclusions The results of this research provide pre-clinical data to warrant further evaluation of statins as potential anti-cancer agents to treat ovarian carcinoma. Many statins are inexpensive, off-patent generic drugs that are immediately available for use as anti-cancer agents. We provide evidence that lovastatin triggers apoptosis of ovarian cancer cells as a single agent by a

  17. Anticancer effect and mechanism of polymer micelle-encapsulated quercetin on ovarian cancer

    Science.gov (United States)

    Gao, Xiang; Wang, Bilan; Wei, Xiawei; Men, Ke; Zheng, Fengjin; Zhou, Yingfeng; Zheng, Yu; Gou, Maling; Huang, Meijuan; Guo, Gang; Huang, Ning; Qian, Zhiyong; Wei, Yuquan

    2012-10-01

    Encapsulation of hydrophobic agents in polymer micelles can improve the water solubility of cargos, contributing to develop novel drugs. Quercetin (QU) is a hydrophobic agent with potential anticancer activity. In this work, we encapsulated QU into biodegradable monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) micelles and tried to provide proof-of-principle for treating ovarian cancer with this nano-formulation of quercetin. These QU loaded MPEG-PCL (QU/MPEG-PCL) micelles with drug loading of 6.9% had a mean particle size of 36 nm, rendering the complete dispersion of quercetin in water. QU inhibited the growth of A2780S ovarian cancer cells on a dose dependent manner in vitro. Intravenous administration of QU/MPEG-PCL micelles significantly suppressed the growth of established xenograft A2780S ovarian tumors through causing cancer cell apoptosis and inhibiting angiogenesis in vivo. Furthermore, the anticancer activity of quercetin on ovarian cancer cells was studied in vitro. Quercetin treatment induced the apoptosis of A2780S cells associated with activating caspase-3 and caspase-9. MCL-1 downregulation, Bcl-2 downregulation, Bax upregulation and mitochondrial transmembrane potential change were observed, suggesting that quercetin may induce apoptosis of A2780S cells through the mitochondrial apoptotic pathway. Otherwise, quercetin treatment decreased phosphorylated p44/42 mitogen-activated protein kinase and phosphorylated Akt, contributing to inhibition of A2780S cell proliferation. Our data suggested that QU/MPEG-PCL micelles were a novel nano-formulation of quercetin with a potential clinical application in ovarian cancer therapy.

  18. High-dose parenteral ascorbate enhanced chemosensitivity of ovarian cancer and reduced toxicity of chemotherapy.

    Science.gov (United States)

    Ma, Yan; Chapman, Julia; Levine, Mark; Polireddy, Kishore; Drisko, Jeanne; Chen, Qi

    2014-02-05

    Ascorbate (vitamin C) was an early, unorthodox therapy for cancer, with an outstanding safety profile and anecdotal clinical benefit. Because oral ascorbate was ineffective in two cancer clinical trials, ascorbate was abandoned by conventional oncology but continued to be used in complementary and alternative medicine. Recent studies provide rationale for reexamining ascorbate treatment. Because of marked pharmacokinetic differences, intravenous, but not oral, ascorbate produces millimolar concentrations both in blood and in tissues, killing cancer cells without harming normal tissues. In the interstitial fluid surrounding tumor cells, millimolar concentrations of ascorbate exert local pro-oxidant effects by mediating hydrogen peroxide (H(2)O(2)) formation, which kills cancer cells. We investigated downstream mechanisms of ascorbate-induced cell death. Data show that millimolar ascorbate, acting as a pro-oxidant, induced DNA damage and depleted cellular adenosine triphosphate (ATP), activated the ataxia telangiectasia mutated (ATM)/adenosine monophosphate-activated protein kinase (AMPK) pathway, and resulted in mammalian target of rapamycin (mTOR) inhibition and death in ovarian cancer cells. The combination of parenteral ascorbate with the conventional chemotherapeutic agents carboplatin and paclitaxel synergistically inhibited ovarian cancer in mouse models and reduced chemotherapy-associated toxicity in patients with ovarian cancer. On the basis of its potential benefit and minimal toxicity, examination of intravenous ascorbate in combination with standard chemotherapy is justified in larger clinical trials.

  19. Human Leukocyte Antigen-Presented Macrophage Migration Inhibitory Factor Is a Surface Biomarker and Potential Therapeutic Target for Ovarian Cancer.

    Science.gov (United States)

    Patterson, Andrea M; Kaabinejadian, Saghar; McMurtrey, Curtis P; Bardet, Wilfried; Jackson, Ken W; Zuna, Rosemary E; Husain, Sanam; Adams, Gregory P; MacDonald, Glen; Dillon, Rachelle L; Ames, Harold; Buchli, Rico; Hawkins, Oriana E; Weidanz, Jon A; Hildebrand, William H

    2016-02-01

    T cells recognize cancer cells via HLA/peptide complexes, and when disease overtakes these immune mechanisms, immunotherapy can exogenously target these same HLA/peptide surface markers. We previously identified an HLA-A2-presented peptide derived from macrophage migration inhibitory factor (MIF) and generated antibody RL21A against this HLA-A2/MIF complex. The objective of the current study was to assess the potential for targeting the HLA-A2/MIF complex in ovarian cancer. First, MIF peptide FLSELTQQL was eluted from the HLA-A2 of the human cancerous ovarian cell lines SKOV3, A2780, OV90, and FHIOSE118hi and detected by mass spectrometry. By flow cytometry, RL21A was shown to specifically stain these four cell lines in the context of HLA-A2. Next, partially matched HLA-A*02:01+ ovarian cancer (n = 27) and normal fallopian tube (n = 24) tissues were stained with RL21A by immunohistochemistry to assess differential HLA-A2/MIF complex expression. Ovarian tumor tissues revealed significantly increased RL21A staining compared with normal fallopian tube epithelium (P < 0.0001), with minimal staining of normal stroma and blood vessels (P < 0.0001 and P < 0.001 compared with tumor cells) suggesting a therapeutic window. We then demonstrated the anticancer activity of toxin-bound RL21A via the dose-dependent killing of ovarian cancer cells. In summary, MIF-derived peptide FLSELTQQL is HLA-A2-presented and recognized by RL21A on ovarian cancer cell lines and patient tumor tissues, and targeting of this HLA-A2/MIF complex with toxin-bound RL21A can induce ovarian cancer cell death. These results suggest that the HLA-A2/MIF complex should be further explored as a cell-surface target for ovarian cancer immunotherapy.

  20. MEIS and PBX homeobox proteins in ovarian cancer

    NARCIS (Netherlands)

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

    2007-01-01

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

  1. Breast and Ovarian Cancer and Family History Risk Categories

    Science.gov (United States)

    ... I J K L M N O P Q R S T U V W X Y Z # Start of Search Controls Search Form Controls Search The CDC Cancel Submit Search The CDC Hereditary Breast and Ovarian Cancer Note: Javascript is disabled or ...

  2. 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...

  3. Pegylated liposomal doxorubicin in the management of ovarian cancer

    Directory of Open Access Journals (Sweden)

    Gabriella Ferrandina

    2010-09-01

    Full Text Available Gabriella Ferrandina1,2, Giacomo Corrado1, Angelo Licameli1, Domenica Lorusso2, Gilda Fuoco1, Salvatore Pisconti3, Giovanni Scambia2 1Gynecologic Oncology Unit, Department of Oncology, Catholic University of Campobasso, Campobasso, Italy; 2Gynecologic Oncology Unit, Catholic University of Rome, Rome, Italy; 3Salvatore Pisconti, Oncology Unit, Taranto Hospital, Taranto, Italy Abstract: Among the pharmaceutical options available for treatment of ovarian cancer, much attention has been progressively focused on pegylated liposomal doxorubicin (PLD, whose unique formulation, which entraps conventional doxorubicin in a bilayer lipidic sphere ­surrounded by a polyethylene glycol layer, prolongs the persistence of the drug in the ­circulation and potentiates intratumor drug accumulation. These properties enable this drug to sustain its very favorable toxicity profile and to be used safely in combination with other drugs. PLD has been already approved for treatment of advanced ovarian cancer patients failing first-line platinum-based treatment. Moreover, phase III trials have been already completed, and results are eagerly awaited, which hopefully will expand the range of PLD clinical application in this neoplasia both in front-line treatment, and in the salvage setting in combination with other drugs. Moreover, attempts are continuing to enable this drug to be combined with novel cytotoxic drugs and target-based agents. This review aims at summarizing the available evidence and the new perspectives for the clinical role of PLD in the management of patients with epithelial ovarian cancer.Keywords: pegylated liposomal doxorubicin, ovarian cancer, clinical trials

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

    NARCIS (Netherlands)

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

    2015-01-01

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

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

    NARCIS (Netherlands)

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

    2015-01-01

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

  6. Tumour suppressor genes in sporadic epithelial ovarian cancer

    DEFF Research Database (Denmark)

    Liu, Ying; Ganesan, Trivadi S

    2002-01-01

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

  7. Feasibility of serodiagnosis of ovarian cancer by mass spectrometry

    DEFF Research Database (Denmark)

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

    2009-01-01

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

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

    NARCIS (Netherlands)

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

    2008-01-01

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

  9. Repeated Intraperitoneal alpha-Radioimmunotherapy of Ovarian Cancer in Mice

    DEFF Research Database (Denmark)

    Elgqvist, Jörgen; Andersson, Håkan; Jensen, Holger;

    2010-01-01

    The aim of this study was to investigate the therapeutic efficacy of alpha-radioimmunotherapy of ovarian cancer in mice using different fractionated treatment regimens. The study was performed using the monoclonal antibody MX35 F(ab')(2) labeled with the alpha-particle emitter (211)At. Methods...

  10. Inhibitory effect of ginsenoside Rg3 on ovarian cancer metastasis

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

  11. Functional redundancy of the Notch pathway in ovarian cancer cell lines.

    Science.gov (United States)

    Silva, Fernanda; Félix, Ana; Serpa, Jacinta

    2016-10-01

    Epithelial ovarian cancer is the most lethal gynecologic malignancy, despite advances in treatment. The most common histological type, high-grade ovarian serous carcinoma (OSC) is usually diagnosed at an advanced stage, and although these types of tumors frequently respond to surgery and platinum-based chemotherapy, they usually recur. Ovarian clear cell carcinoma (OCCC) is an unusual histological type, which is known to be intrinsically chemoresistant and is associated with poor prognosis in advanced stages. In recent years, genetic alterations and epigenetic modulation of signaling pathways have been reported in OSC and OCCC, including the overexpression of Notch pathway elements and histone deacetylases. Histone deacetylase inhibitors (HDACis), including vorinostat (suberoylanilide hydroxamic acid), alter the transcription of genes involved in cell growth, survival and apoptosis, and have become an attractive therapeutic approach. However, no previous work has addressed the effect of HDACis, and in particular vorinostat, on Notch signaling in ovarian cancer. Therefore, the present study aimed to investigate the modulation of the Notch pathway by vorinostat in ovarian cancer. Using immunofluorescence and quantitative polymerase chain reaction, the present results revealed that vorinostat activated the Notch pathway in OCCC and OSC cell lines, through different Notch ligands. In OCCC, the activation of the Notch pathway appeared to occur through Delta-like (Dll) ligands 1, 2 and 3, whereas in OSC Dll1 and Jagged 1 and 2 ligands were involved. The activation of the Notch pathway by vorinostat, in OCCC and OSC cell lines, culminated in the increased expression of the same downstream transcription factors, hairy enhancer of split (Hes) 1 and 5, and Hes-related proteins 1 and 2. In conclusion, vorinostat modulates the expression of several downstream targets of the Notch pathway and independent Notch receptors and ligands that are expressed in OSC and OCCC. This

  12. 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.

  13. First-line therapy in ovarian cancer trials.

    Science.gov (United States)

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

    2011-05-01

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

  14. Lymphadenectomy in surgical stage I epithelial ovarian cancer

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  15. Metformin prevents aggressive ovarian cancer growth driven by high-energy diet: similarity with calorie restriction.

    Science.gov (United States)

    Al-Wahab, Zaid; Mert, Ismail; Tebbe, Calvin; Chhina, Jasdeep; Hijaz, Miriana; Morris, Robert T; Ali-Fehmi, Rouba; Giri, Shailendra; Munkarah, Adnan R; Rattan, Ramandeep

    2015-05-10

    Caloric restriction (CR) was recently demonstrated by us to restrict ovarian cancer growth in vivo. CR resulted in activation of energy regulating enzymes adenosine monophosphate activated kinase (AMPK) and sirtuin 1 (SIRT1) followed by downstream inhibition of Akt-mTOR. In the present study, we investigated the effects of metformin on ovarian cancer growth in mice fed a high energy diet (HED) and regular diet (RD) and compared them to those seen with CR in an immunocompetent isogeneic mouse model of ovarian cancer. Mice either on RD or HED diet bearing ovarian tumors were treated with 200 mg/kg metformin in drinking water. Metformin treatment in RD and HED mice resulted in a significant reduction in tumor burden in the peritoneum, liver, kidney, spleen and bowel accompanied by decreased levels of growth factors (IGF-1, insulin and leptin), inflammatory cytokines (MCP-1, IL-6) and VEGF in plasma and ascitic fluid, akin to the CR diet mice. Metformin resulted in activation of AMPK and SIRT1 and inhibition of pAkt and pmTOR, similar to CR. Thus metformin can closely mimic CR's tumor suppressing effects by inducing similar metabolic changes, providing further evidence of its potential not only as a therapeutic drug but also as a preventive agent.

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

    Science.gov (United States)

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

    2015-10-01

    Ovarian cancer is the most lethal gynecological malignancy. It is usually diagnosed at a late stage, with a 5-yr survival rate of metastasis. Although metastasis plays a crucial role in promoting ovarian tumor progression and decreasing patient survival rates, the underlying mechanisms of ovarian cancer spread have yet to be thoroughly explored. For many years, researchers have believed that ovarian cancer metastasizes via a passive mechanism by which ovarian cancer cells are shed from the primary tumor and carried by the physiological movement of peritoneal fluid to the peritoneum and omentum. However, the recent discovery of hematogenous metastasis of ovarian cancer to the omentum via circulating tumor cells instigated rethinking of the mode of ovarian cancer metastasis and the importance of the "seed-and-soil" hypothesis for ovarian cancer metastasis. In this review we discuss the possible mechanisms by which ovarian cancer cells metastasize from the primary tumor to the omentum, the cross-talk signaling events between ovarian cancer cells and various stromal cells that play crucial roles in ovarian cancer metastasis, and the possible clinical implications of these findings in the management of this deadly, highly metastatic disease.

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

    Institute of Scientific and Technical Information of China (English)

    陈颖; 赵雨杰; 郑华川; 杨雪飞; 汪桂兰; 辛彦

    2003-01-01

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

  18. Clinical utility of trabectedin for the treatment of ovarian cancer: current evidence

    Directory of Open Access Journals (Sweden)

    Mascilini F

    2014-07-01

    Full Text Available Floriana Mascilini,* Giulia Amadio,* Maria Grazia Di Stefano, Manuela Ludovisi, Alessia Di Legge, Carmine Conte, Rosa De Vincenzo, Caterina Ricci, Valeria Masciullo, Vanda Salutari, Giovanni Scambia, Gabriella FerrandinaGynecologic Oncology Unit, Department of Oncology, Catholic University of Rome, Italy  *These authors contributed equally to this work Abstract: Among the pharmaceutical options available for treatment of ovarian cancer, attention has been increasingly focused on trabectedin (ET-743, a drug which displays a unique mechanism of action and has been shown to be active in several human malignancies. Currently, single agent trabectedin is approved for treatment of patients with advanced soft tissue sarcoma after failure of anthracyclines and ifosfamide, and in association with pegylated liposomal doxorubicin for treatment of patients with relapsed partially platinum-sensitive ovarian cancer. This review aims at summarizing the available evidence about the clinical role of trabectedin in the management of patients with epithelial ovarian cancer. Novel perspectives coming from a better understanding of trabectedin mechanisms of action and definition of patients subgroups likely susceptible to benefit of trabectedin treatment are also presented. Keywords: ET-743, ovarian cancer, clinical trials

  19. Synergistic cytotoxic effect of sulindac and pyrrolidine dithiocarbamate against ovarian cancer cells.

    Science.gov (United States)

    Jakubowska-Mućka, Anna; Sieńko, Jacek; Zapała, Łukasz; Wolny, Rafał; Lasek, Witold

    2012-04-01

    Sulindac, a non-steroidal anti-inflammatory drug, suppresses carcinogenesis and inhibits growth of tumor cells. Pyrrolidine dithiocarbamate (PDTC), a potent NF-κB inhibitor, has been also identified as a potential anti-neoplastic agent. We hypothesized that combination of sulindac and PDTC could result in augmentation of cytotoxicity against ovarian cancer cells. The effect of sulindac and PDTC was examined on several ovarian cancer lines. Tumor cell viability was assessed using the MTT assay. Annexin-V/PI staining was used to detect apoptosis, cell cycle distribution was analyzed in FACS, and expression of cellular proteins was detected by western blotting. Incubation of OVA-14, OVP-10 and CAOV-1 ovarian cancer cells with sulindac and PDTC resulted in significantly greater inhibition of cell viability compared to either compound alone. In a model of OVA-14 cells it was evident that this effect was not related to the expression of COX enzymes since both active (sulindac sulfide) and inactive (sulindac) in vitro compounds affected the growth of tumor cells to a similar extent and synergized in cytotoxicity with PDTC. Combination of sulindac and PDTC lead to G0 arrest and massive apoptosis in co-treated cultures. Western blotting analysis argued for induction of the mitochondrial apoptotic pathway. These data demonstrate the synergistic cytotoxic effect of sulindac and PDTC on ovarian cancer cells through apoptosis and cell cycle arrest and prompt to test the efficacy of this combination in animal models.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    200 genes in the NF-κB pathway for a total of 2,282 SNPs (including rs17561) for genotype analysis of 15,604 cases of ovarian cancer in patients of European descent, including 6,179 of high-grade serous (HGS), 2,100 endometrioid, 1,591 mucinous, 1,034 clear cell, and 1,016 low-grade serous, including......A missense single-nucleotide polymorphism (SNP) in the immune modulatory gene IL1A has been associated with ovarian cancer risk (rs17561). Although the exact mechanism through which this SNP alters risk of ovarian cancer is not clearly understood, rs17561 has also been associated with risk...... of endometriosis, an epidemiologic risk factor for ovarian cancer. Interleukin-1α (IL1A) is both regulated by and able to activate NF-κB, a transcription factor family that induces transcription of many proinflammatory genes and may be an important mediator in carcinogenesis. We therefore tagged SNPs in more than...

  1. 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.

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  3. 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...

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

    NARCIS (Netherlands)

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

    2015-01-01

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

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  6. Effect of the BRCA1-SIRT1-EGFR axis on cisplatin sensitivity in ovarian cancer.

    Science.gov (United States)

    Li, Da; Wu, Qi-Jun; Bi, Fang-Fang; Chen, Si-Lei; Zhou, Yi-Ming; Zhao, Yue; Yang, Qing

    2016-01-01

    There is accumulating evidence that breast cancer 1 (BRCA1), sirtuin 1 (SIRT1), and epidermal growth factor receptor (EGFR) help to modulate cisplatin cytotoxicity. The role of dynamic crosstalk among BRCA1, SIRT1, and EGFR in cisplatin sensitivity remains largely unknown. We found that BRCA1, SIRT1, and EGFR levels were increased in cisplatin-resistant ovarian cancers compared with those in cisplatin-sensitive ovarian cancers. Hypomethylation in the BRCA1 promoter was associated with BRCA1 activation, significantly elevated SIRT1 levels, decreased nicotinamide adenine dinucleotide (NAD)-mediated SIRT1 activity, and decreased EGFR levels. Treatment with 5 and 10 μg/ml cisplatin induced a gradual increase in BRCA1 and SIRT1 levels and a gradual decrease in NAD levels and NAD-mediated SIRT1 activity, whereas EGFR levels were increased or decreased by treatment with 5 or 10 μg/ml cisplatin, respectively. The overexpression of SIRT1 or the enhancement of SIRT1 activity synergistically enhanced the BRCA1-mediated effects on EGFR transcription. In contrast, the knockdown of SIRT1 or the inhibition of SIRT1 activity inhibited the BRCA1-mediated effects on EGFR transcription. BRCA1 regulates EGFR through a BRCA1-mediated balance between SIRT1 expression and activity. Those results improve our understanding of the basic molecular mechanism underlying BRCA1-related cisplatin resistance in ovarian cancer.

  7. 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.

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

    Science.gov (United States)

    2015-09-01

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

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

    OpenAIRE

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

    2016-01-01

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

  10. 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.

  11. 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.

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

    Institute of Scientific and Technical Information of China (English)

    Ze-Hua Wang; Cong-Jian Xu

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Katarzyna M. Terlikowska

    2014-11-01

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

  14. A review of HER2-targeted therapy in breast and ovarian cancer: lessons from antiquity - CLEOPATRA and PENELOPE.

    Science.gov (United States)

    Hodeib, Melissa; Serna-Gallegos, Tasha; Tewari, Krishnansu S

    2015-01-01

    Although breast and ovarian cancer have notable distinctions, there may exist parallel pathways that can be exploited for therapeutic gain. For example, the therapeutic arena in breast cancer has benefited greatly from available endocrine therapies as well as novel drugs designed to target the HER2 receptor, including trastuzumab, lapatinib, T-DM1 and pertuzumab. CLEOPATRA, a Phase III randomized clinical trial studying pertuzumab in women with HER2-amplified metastatic breast cancer, was practice-changing in 2014. Its counterpart, the Phase III randomized PENELOPE trial, was activated following promising Phase II data and studied pertuzumab in an enriched ovarian cancer patient population with low HER3 mRNA. This review will trace the development of anti-HER2 therapies in breast and ovarian cancer.

  15. 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.

  16. 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

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

    Science.gov (United States)

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

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

    Institute of Scientific and Technical Information of China (English)

    程琪辉; 张喜平; 曾小澜

    2003-01-01

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

  19. Angiogenesis-Related Pathways in the Pathogenesis of Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Aristotle Bamias

    2013-07-01

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

  20. 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.

  1. Cancer Associated Fibroblasts express pro-inflammatory factors in human breast and ovarian tumors

    Energy Technology Data Exchange (ETDEWEB)

    Erez, Neta, E-mail: netaerez@post.tau.ac.il [Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel-Aviv 69978 (Israel); Glanz, Sarah [Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel-Aviv 69978 (Israel); Raz, Yael [Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel-Aviv 69978 (Israel); Department of Obstetrics and Gynecology, LIS Maternity Hospital, Tel Aviv Sourasky Medical Center, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel); Avivi, Camilla [Department of Pathology, Sheba Medical Center, Tel Hashomer, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel); Barshack, Iris [Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel-Aviv 69978 (Israel); Department of Pathology, Sheba Medical Center, Tel Hashomer, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel)

    2013-08-02

    Highlights: •CAFs in human breast and ovarian tumors express pro-inflammatory factors. •Expression of pro-inflammatory factors correlates with tumor invasiveness. •Expression of pro-inflammatory factors is associated with NF-κb activation in CAFs. -- Abstract: Inflammation has been established in recent years as a hallmark of cancer. Cancer Associated Fibroblasts (CAFs) support tumorigenesis by stimulating angiogenesis, cancer cell proliferation and invasion. We previously demonstrated that CAFs also mediate tumor-enhancing inflammation in a mouse model of skin carcinoma. Breast and ovarian carcinomas are amongst the leading causes of cancer-related mortality in women and cancer-related inflammation is linked with both these tumor types. However, the role of CAFs in mediating inflammation in these malignancies remains obscure. Here we show that CAFs in human breast and ovarian tumors express high levels of the pro-inflammatory factors IL-6, COX-2 and CXCL1, previously identified to be part of a CAF pro-inflammatory gene signature. Moreover, we show that both pro-inflammatory signaling by CAFs and leukocyte infiltration of tumors are enhanced in invasive ductal carcinoma as compared with ductal carcinoma in situ. The pro-inflammatory genes expressed by CAFs are known NF-κB targets and we show that NF-κB is up-regulated in breast and ovarian CAFs. Our data imply that CAFs mediate tumor-promoting inflammation in human breast and ovarian tumors and thus may be an attractive target for stromal-directed therapeutics.

  2. Growth Inhibition and Apoptosis Inducing Mechanisms of Curcumin on Human Ovarian Cancer Cell Line A2780

    Institute of Scientific and Technical Information of China (English)

    ZHENG Li-duan; TONG Qiang-song; WU Cui-huan

    2006-01-01

    Objective: To explore the growth inhibition effects and apoptosis inducing mechanisms of curcumin on human ovarian cancer cell line A2780. Methods: After treatment with 10-50 μmol/L curcumin for 6-24 h, the growth activity of A2780 cancer cells were studied by [ 4, 5-dimethylthiazol-2-yl]-2, 5-diphenyItetrazolium bromide (MTT) colorimetry. Cellular apoptosis was inspected by flow cytometery and acridine orange-ethidium bromide fluorescent staining methods. The fragmentation of cellular chromosome DNA was detected by DNA ladder, the ultrastructural change was observed under a transmission electron microscope,and the protein levels of nuclear factor-kappa B (NF-κB, P65) and cysteinyl aspartate specific protease-3 (Caspase-3) in ovarian cancer cells were measured by immunohistochemistry. Results: After treatment with various concentrations of curcumin, the growth inhibition rates of cancer cells reached 62.05%- 89.24%,with sub-G1 peaks appearing on histogram. Part of the cancer cells showed characteristic morphological changes of apoptosis under fluorescence and electron microscopes, and the rate of apoptosis was 21.5 % -33.5%. The protein expression of NF-κB was decreased, while that of Caspase-3 was increased in a timedependent manner. Conclusion: Curcumin could significantly inhibit the growth of human ovarian cancer cells;inducing apoptosis through up-regulating Caspase-3 and down-regulating gene expression of NF-κB is probably one of its molecular mechanisms.

  3. 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.

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

    Institute of Scientific and Technical Information of China (English)

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

    2004-01-01

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

  5. RAD51C germline mutations in breast and ovarian cancer cases from high-risk families.

    Directory of Open Access Journals (Sweden)

    Jessica Clague

    Full Text Available BRCA1 and BRCA2 are the most well-known breast cancer susceptibility genes. Additional genes involved in DNA repair have been identified as predisposing to breast cancer. One such gene, RAD51C, is essential for homologous recombination repair. Several likely pathogenic RAD51C mutations have been identified in BRCA1- and BRCA2-negative breast and ovarian cancer families. We performed complete sequencing of RAD51C in germline DNA of 286 female breast and/or ovarian cancer cases with a family history of breast and ovarian cancers, who had previously tested negative for mutations in BRCA1 and BRCA2. We screened 133 breast cancer cases, 119 ovarian cancer cases, and 34 with both breast and ovarian cancers. Fifteen DNA sequence variants were identified; including four intronic, one 5' UTR, one promoter, three synonymous, and six non-synonymous variants. None were truncating. The in-silico SIFT and Polyphen programs were used to predict possible pathogenicity of the six non-synonomous variants based on sequence conservation. G153D and T287A were predicted to be likely pathogenic. Two additional variants, A126T and R214C alter amino acids in important domains of the protein such that they could be pathogenic. Two-hybrid screening and immunoblot analyses were performed to assess the functionality of these four non-synonomous variants in yeast. The RAD51C-G153D protein displayed no detectable interaction with either XRCC3 or RAD51B, and RAD51C-R214C displayed significantly decreased interaction with both XRCC3 and RAD51B (p<0.001. Immunoblots of RAD51C-Gal4 activation domain fusion peptides showed protein levels of RAD51C-G153D and RAD51C-R214C that were 50% and 60% of the wild-type, respectively. Based on these data, the RAD51C-G153D variant is likely to be pathogenic, while the RAD51C- R214C variant is hypomorphic of uncertain pathogenicity. These results provide further support that RAD51C is a rare breast and ovarian cancer susceptibility gene.

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

    Science.gov (United States)

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

    2015-12-01

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

  7. Bevacizumab in Ovarian Cancer: State of the Art and Unanswered Questions.

    Science.gov (United States)

    Musella, Angela; Vertechy, Laura; Romito, Alessia; Marchetti, Claudia; Giannini, Andrea; Sciuga, Valentina; Bracchi, Carlotta; Tomao, Federica; Di Donato, Violante; De Felice, Francesca; Monti, Marco; Muzii, Ludovico; Benedetti Panici, Pierluigi

    2017-01-01

    Ovarian cancer is a most lethal gynecologic tumor. The mainstay treatment is cytoreductive surgery followed by platinum-based chemotherapy. However, a high percentage of patients recur, thus needing multiple treatments with a frequently poor prognosis. In the last two decades, research has focused on the potential of target therapies to improve the survival of patients affected by ovarian cancer. Bevacizumab is one of the most studied target therapies, and it is approved for first- and second-line treatment of advanced epithelial ovarian, fallopian tube, and primary peritoneal tumors. Despite its widespread use with favorable results, controversy regarding patient selection and the best schedule, dosage, and timing of bevacizumab still exists. This review summarizes the state of the art on the use of bevacizumab for ovarian cancer in front-line, recurrence, and neoadjuvant settings. This study focuses on the results of pivotal trials, emerging data, ongoing research, and still unanswered questions about the most adequate dosage of bevacizumab and its potential activity after disease progression or rechallenge in previously treated patients.

  8. 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...

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  10. 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...

  11. Optimizing patient derived mesenchymal stem cells as virus carriers for a Phase I clinical trial in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Mader Emily K

    2013-01-01

    Full Text Available Abstract Background Mesenchymal stem cells (MSC can serve as carriers to deliver oncolytic measles virus (MV to ovarian tumors. In preparation for a clinical trial to use MSC as MV carriers, we obtained cells from ovarian cancer patients and evaluated feasibility and safety of this approach. Methods MSC from adipose tissues of healthy donors (hMSC and nine ovarian cancer patients (ovMSC were characterized for susceptibility to virus infection and tumor homing abilities. Results Adipose tissue (range 0.16-3.96 grams from newly diagnosed and recurrent ovarian cancer patients yielded about 7.41×106 cells at passage 1 (range 4–9 days. Phenotype and doubling times of MSC were similar between ovarian patients and healthy controls. The time to harvest of 3.0×108 cells (clinical dose could be achieved by day 14 (range, 9–17 days. Two of nine samples tested had an abnormal karyotype represented by trisomy 20. Despite receiving up to 1.6×109 MSC/kg, no tumors were seen in SCID beige mice and MSC did not promote the growth of SKOV3 human ovarian cancer cells in mice. The ovMSC migrated towards primary ovarian cancer samples in chemotaxis assays and to ovarian tumors in athymic mice. Using non-invasive SPECT-CT imaging, we saw rapid co-localization, within 5–8 minutes of intraperitoneal administration of MV infected MSC to the ovarian tumors. Importantly, MSC can be pre-infected with MV, stored in liquid nitrogen and thawed on the day of infusion into mice without loss of activity. MV infected MSC, but not virus alone, significantly prolonged the survival of measles immune ovarian cancer bearing animals. Conclusions These studies confirmed the feasibility of using patient derived MSC as carriers for oncolytic MV therapy. We propose an approach where MSC from ovarian cancer patients will be expanded, frozen and validated to ensure compliance with the release criteria. On the treatment day, the cells will be thawed, washed, mixed with virus, briefly

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

    Science.gov (United States)

    2014-10-01

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

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

    OpenAIRE

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

    2013-01-01

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

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

    OpenAIRE

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

    1991-01-01

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

  15. The Epidermal Growth Factor Receptor Responsive miR-125a Represses Mesenchymal Morphology in Ovarian Cancer Cells

    Directory of Open Access Journals (Sweden)

    Karen D. Cowden Dahl

    2009-11-01

    Full Text Available The epithelial-to-mesenchymal transition (EMT that occurs during embryonic development is recapitulated during tumor metastasis. Important regulators of this process include growth factors, transcription factors, and adhesion molecules. New evidence suggests that microRNA (miRNA activity contributes to metastatic progression and EMT; however, the mechanisms leading to altered miRNA expression during cancer progression remain poorly understood. Importantly, overexpression of the epidermal growth factor receptor (EGFR in ovarian cancer correlates with poor disease outcome and induces EMT in ovarian cancer cells. We report that EGFR signaling leads to transcriptional repression of the miRNA miR-125a through the ETS family transcription factor PEA3. Overexpression of miR-125a induces conversion of highly invasive ovarian cancer cells from a mesenchymal to an epithelial morphology, suggesting miR-125a is a negative regulator of EMT. We identify AT-rich interactive domain 3B (ARID3B as a target of miR-125a and demonstrate that ARID3B is overexpressed in human ovarian cancer. Repression of miR-125a through growth factor signaling represents a novel mechanism for regulating ovarian cancer invasive behavior.

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

    NARCIS (Netherlands)

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

    2005-01-01

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

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

    NARCIS (Netherlands)

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

    2015-01-01

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

  18. 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

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

    NARCIS (Netherlands)

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

    2008-01-01

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

  20. Squalamine and cisplatin block angiogenesis and growth of human ovarian cancer cells with or without HER-2 gene overexpression.

    Science.gov (United States)

    Li, Dan; Williams, Jon I; Pietras, Richard J

    2002-04-25

    Angiogenesis is important for growth and progression of ovarian cancers. Squalamine is a natural antiangiogenic sterol, and its potential role in treatment of ovarian cancers with or without standard cisplatin chemotherapy was assessed. Since HER-2 gene overexpression is associated with cisplatin resistance in vitro and promotion of tumor angiogenesis in vivo, the response of ovarian cancer cells with or without HER-2 gene overexpression to squalamine and cisplatin was evaluated both in tumor xenograft models and in tissue culture. Ovarian cancer cells with or without HER-2 overexpression were grown as subcutaneous xenografts in nude mice. Animals were treated by intraperitoneal injection with control vehicle, cisplatin, squalamine or cisplatin combined with squalamine. At the end of the experiment, tumors were assessed for tumor growth inhibition and for changes in microvessel density and apoptosis. Additional in vitro studies evaluated effects of squalamine on tumor and endothelial cell growth and on signaling pathways in human endothelial cells. Profound growth inhibition was elicited by squalamine alone and by combined treatment with squalamine and cisplatin for both parental and HER-2-overexpressing ovarian tumor xenografts. Immunohistochemical evaluation of tumors revealed decreased microvessel density and increased apoptosis. Although HER-2-overexpressing tumors had more angiogenic and less apoptotic activity than parental cancers, growth of both tumor types was similarly suppressed by treatment with squalamine combined with cisplatin. In in vitro studies, we found that squalamine does not directly affect proliferation of ovarian cells. However, squalamine significantly blocked VEGF-induced activation of MAP kinase and cell proliferation in human vascular endothelial cells. The results suggest that squalamine is anti-angiogenic for ovarian cancer xenografts and appears to enhance cytotoxic effects of cisplatin chemotherapy independent of HER-2 tumor status.

  1. [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.

  2. Ovarian Cancer Surgery: Health and Coping during Perioperative Period

    DEFF Research Database (Denmark)

    Hounsgaard, Lise; Seibæk, L.; Petersen, L.;

    2013-01-01

    -up questionnaire study in which the Short Form-36 Questionnaire was used to survey general health twice during the perioperative period and the Life Orientation Questionnaire (SOC) was used once to define the postoperative coping capacity. An evidence-based, preoperative supportive care programme was subsequently......PURPOSE: The study objective was to survey general health and coping in women undergoing ovarian cancer surgery, and subsequently to develop and test a supportive care intervention. METHODS/MATERIALS: Women who underwent surgery on the suspicion of ovarian cancer participated in a follow...... developed and tested. This consisted of lean methodology applied to clinical pathways, preoperative optimisation, and psychosocial care and support. RESULTS: From 294 women allocated to three study groups, a total of 546 Short Form-36 questionnaires and 253 SOC questionnaires were available for analysis...

  3. Epidemiology and etiology of ovarian cancer: a review

    Energy Technology Data Exchange (ETDEWEB)

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

    1985-07-01

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

  4. 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.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Al-Asari Sami

    2012-09-01

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

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

    Science.gov (United States)

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

    1991-01-01

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

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  9. 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.

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

    Science.gov (United States)

    2014-04-01

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

  11. Pegylated liposomal doxorubicin in the management of ovarian cancer

    OpenAIRE

    Ferrandina, Gabriella

    2010-01-01

    Gabriella Ferrandina1,2, Giacomo Corrado1, Angelo Licameli1, Domenica Lorusso2, Gilda Fuoco1, Salvatore Pisconti3, Giovanni Scambia2 1Gynecologic Oncology Unit, Department of Oncology, Catholic University of Campobasso, Campobasso, Italy; 2Gynecologic Oncology Unit, Catholic University of Rome, Rome, Italy; 3Salvatore Pisconti, Oncology Unit, Taranto Hospital, Taranto, Italy Abstract: Among the pharmaceutical options available for treatment of ovarian cancer, much attention has been progressi...

  12. Junk DNA-Encoded Antigens in Ovarian Cancer

    Science.gov (United States)

    2014-10-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  14. Targeting Signaling Pathways in Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Johannes Haybaeck

    2013-05-01

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

  15. Retrospective study of the impact of pharmacogenetic variants on paclitaxel toxicity and survival in patients with ovarian cancer

    DEFF Research Database (Denmark)

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

    2011-01-01

    Paclitaxel has a broad spectrum of anti-tumor activity and is useful in the treatment of ovarian, breast, and lung cancer. Paclitaxel is metabolized in the liver by CYP2C8 and CYP3A4 and transported by P-glycoprotein. The dose-limiting toxicities are neuropathy and neutropenia, but the interindiv......Paclitaxel has a broad spectrum of anti-tumor activity and is useful in the treatment of ovarian, breast, and lung cancer. Paclitaxel is metabolized in the liver by CYP2C8 and CYP3A4 and transported by P-glycoprotein. The dose-limiting toxicities are neuropathy and neutropenia...

  16. Cleaved forms of the urokinase plasminogen activator receptor in plasma have diagnostic potential and predict postoperative survival in patients with ovarian cancer

    DEFF Research Database (Denmark)

    Henic, E.; Borgfeldt, C.; Christensen, I.J.;

    2008-01-01

    -FIA 3 measuring the liberated uPAR(I). Tumors were classified as benign (n = 211), borderline (possibly malignant; n = 30), and well (n = 19), moderately (n = 15), and poorly (n = 60) differentiated malignant. RESULTS: All uPAR forms as well as CA125 were statistically significant in univariate analysis...... (95% CI), 0.90-0.98] as well as borderline and benign tumors (AUC, 0.78; 95% CI, 0.67-0.89). All suPAR forms were markers for poor prognosis in univariate analyses, and high preoperative plasma level of uPAR(I) is an independent predictor of poor prognosis (hazard ratio, 1.84; 95% CI, 1.15-2.95; P = 0.......011) in multivariate analyses including age and CA125. CONCLUSIONS: High concentration of plasma uPAR(I) is an independent preoperative marker of poor prognosis in patients with ovarian cancer. The combination of plasma suPAR(I-III) + suPAR(II-III) and CA125 discriminates between malignant and benign tumors...

  17. A novel proteomic biomarker panel as a diagnostic tool for patients with ovarian cancer

    DEFF Research Database (Denmark)

    Høgdall, Claus; Fung, Eric T; Christensen, Ib J;

    2011-01-01

    Previous reports have shown that the proteomic markers apolipoprotein A1, hepcidin, transferrin, inter-alpha trypsin IV internal fragment, transthyretin, connective-tissue activating protein 3 and beta-2 microglobulin may discriminate between a benign pelvic mass and ovarian cancer (OC). The aim...... was to determine if these serum proteomic biomarkers alone as well as in combination with age and serum CA125, could be helpful in triage of women with a pelvic mass....

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

    Science.gov (United States)

    2001-09-01

    Pharmacol 1997;54:541-4. phosphatidic acid phosphatases (PAPs), sphingomyelinase, and 6. Bookman MA. Biological therapy of ovarian cancer: Current...smooth muscle cells in culture. Thrombosis Res WH. Lysophosphatidic acid induces neuronal shape changes via 1999;94:317-26. a novel receptor-mediated...2001 9 healing agenit--sph~igo~sylphosphorylcholinie. J Investig Derma- phosphatidic acid -stimulated mritogeii-activated protein kinase tol 1996;106:232

  19. Ovarian Metastasis from Lung Cancer: A Rare Entity

    Directory of Open Access Journals (Sweden)

    Huseyin Cengiz

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Bristow Robert E

    2009-07-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  2. NOXA-induced alterations in the Bax/Smac axis enhance sensitivity of ovarian cancer cells to cisplatin.

    Directory of Open Access Journals (Sweden)

    Chao Lin

    Full Text Available Ovarian cancer is the most common cause of death from gynecologic malignancy. Deregulation of p53 and/or p73-associated apoptotic pathways contribute to the platinum-based resistance in ovarian cancer. NOXA, a pro-apoptotic BH3-only protein, is identified as a transcription target of p53 and/or p73. In this study, we found that genetic variants of Bcl-2 proteins exist among cisplatin-sensitive and -resistant ovarian cancer cells, and the responses of NOXA and Bax to cisplatin are regulated mainly by p53. We further evaluated the effect of NOXA on cisplatin. NOXA induced apoptosis and sensitized A2780s and SKOV3 cells to cisplatin in vitro and in vivo. The effects were mediated by elevated Bax expression, enhanced caspase activation, release of Cyt C and Smac into the cytosol. Furthermore, gene silencing of Bax or Smac significantly attenuated NOXA and/or cisplatin-induced apoptosis in chemosensitive A2780s cells, whereas overexpression of Bax or addition of Smac-N7 peptide significantly increased NOXA and/or cisplatin-induced apoptosis in chemoresistant SKOV3 cells. To our knowledge, these data suggest a new mechanism by which NOXA chemosensitized ovarian cancer cells to cisplatin by inducing alterations in the Bax/Smac axis. Taken together, our findings show that NOXA is potentially useful as a chemosensitizer in ovarian cancer therapy.

  3. NOXA-induced alterations in the Bax/Smac axis enhance sensitivity of ovarian cancer cells to cisplatin.

    Science.gov (United States)

    Lin, Chao; Zhao, Xin-yu; Li, Lei; Liu, Huan-yi; Cao, Kang; Wan, Yang; Liu, Xin-yu; Nie, Chun-lai; Liu, Lei; Tong, Ai-ping; Deng, Hong-xin; Li, Jiong; Yuan, Zhu; Wei, Yu-quan

    2012-01-01

    Ovarian cancer is the most common cause of death from gynecologic malignancy. Deregulation of p53 and/or p73-associated apoptotic pathways contribute to the platinum-based resistance in ovarian cancer. NOXA, a pro-apoptotic BH3-only protein, is identified as a transcription target of p53 and/or p73. In this study, we found that genetic variants of Bcl-2 proteins exist among cisplatin-sensitive and -resistant ovarian cancer cells, and the responses of NOXA and Bax to cisplatin are regulated mainly by p53. We further evaluated the effect of NOXA on cisplatin. NOXA induced apoptosis and sensitized A2780s and SKOV3 cells to cisplatin in vitro and in vivo. The effects were mediated by elevated Bax expression, enhanced caspase activation, release of Cyt C and Smac into the cytosol. Furthermore, gene silencing of Bax or Smac significantly attenuated NOXA and/or cisplatin-induced apoptosis in chemosensitive A2780s cells, whereas overexpression of Bax or addition of Smac-N7 peptide significantly increased NOXA and/or cisplatin-induced apoptosis in chemoresistant SKOV3 cells. To our knowledge, these data suggest a new mechanism by which NOXA chemosensitized ovarian cancer cells to cisplatin by inducing alterations in the Bax/Smac axis. Taken together, our findings show that NOXA is potentially useful as a chemosensitizer in ovarian cancer therapy.

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

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

  5. Symptom interpretation and health care seeking in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Blaakaer Jan

    2011-06-01

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

  6. 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.

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

    Directory of Open Access Journals (Sweden)

    Geun Ok Jeong

    2013-07-01

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

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

    NARCIS (Netherlands)

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

    2010-01-01

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

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  10. BRCA1 deficiency increases the sensitivity of ovarian cancer cells to auranofin

    Energy Technology Data Exchange (ETDEWEB)

    Oommen, Deepu [School of Biological Sciences, Plymouth University, Plymouth PL4 8AA (United Kingdom); Yiannakis, Dennis [Plymouth Oncology Centre, Derriford Hospital, Plymouth Hospitals NHS Trust, Plymouth PL6 8DH (United Kingdom); Jha, Awadhesh N., E-mail: a.jha@plymouth.ac.uk [School of Biological Sciences, Plymouth University, Plymouth PL4 8AA (United Kingdom)

    2016-02-15

    Highlights: • BRCA1 deficient cancer cells exhibit increased DNA damage upon auranofin treatment. • Auranofin induces apoptosis in BRCA1 deficient cancer cells despite the activation of Nrf2. • Antioxidant protects BRCA1 deficient cancer cells from auranofin. - Abstract: Auranofin, a thioredoxin reductase inhibitor and an anti-rheumatic drug is currently undergoing phase 2 clinical studies for repurposing to treat recurrent epithelial ovarian cancer. Previous studies have established that auranofin exerts its cytotoxic activity by increasing the production of reactive oxygen species (ROS). Breast cancer 1, early onset (BRCA1) is a DNA repair protein whose functional status is critical in the prognosis of ovarian cancer. Apart from its key role in DNA repair, BRCA1 is also known to modulate cellular redox homeostasis by regulating the stability of anti-oxidant transcription factor, nuclear factor erythroid 2—related factor 2 (Nrf2) via direct protein–protein interaction. However, it is currently unknown whether BRCA1 modulates the sensitivity of ovarian cancer cells to auranofin. Here we report that BRCA1-depleted cells exhibited increased DNA double strand breaks (DSBs) and decreased clonogenic cell survival upon auranofin treatment. Interestingly, auranofin induced the expression of Nrf2 in BRCA1-depleted cells suggesting its regulation independent of BRCA1. Furthermore, anti-oxidant agent, N-acetyl cysteine (NAC) protected BRCA1-depleted cells from DNA damage and apoptosis induced by auranofin. Our study suggests that accumulated lethal DSBs resulting from the oxidative damage render BRCA1 deficient cells more sensitive to auranofin despite the activation of Nrf2.

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

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

  12. Apoptotic and genomic effects of corilagin on SKOV3 ovarian cancer cell line

    Science.gov (United States)

    Attar, Rukset; Cincin, Zeynep Birsu; Bireller, Elif Sinem; Cakmakoglu, Bedia

    2017-01-01

    Corilagin is a member of the tannin family and has been isolated from traditional Chinese medicinal plants, such as Phyllanthus spp. Corilagin has anti-inflammatory, antioxidative, antiatherogenic, and antihypertensive effects in various experimental models. In this research, we aimed to investigate for the first time whether corilagin had apoptotic and genomic effects in ovarian cancer treatment in the same study. The potential apoptotic of corilagin was investigated using a WST1 cell proliferation test, caspase 3, and mitochondrial membrane potential JC1 assays in a time- and dose-dependent manner. Genomic changes in expression levels against corilagin treatment were measured using an Illumina human HT-12V4 BeadChip microarray. Bioinformatic data analyses were performed using GenomeStudio and Ingenuity Pathway Analysis software. The data of our study demonstrated that there were statistically significant time- and dose-dependent increases in caspase 3 enzymatic activity and loss of mitochondrial membrane potential in line with decreases in cancer cell proliferation. According to gene-ontology analysis, we found that adherens junctions, antigen processing and presentation, and the phosphatidylinositol signaling system were the most statistically significant networks in response to corilagin treatment on SKOV3 cells, in a time- and dose-dependent manner. The apoptotic and genome-wide effects of corilagin on ovarian cancer cells were examined in detail for the first time in the literature. The results of our study suggest that corilagin might have the potential to be used as a new treatment option for epithelial ovarian cancer.

  13. Antiproliferation effect of Rosemary (Rosmarinus officinalis) on human ovarian cancer cells in vitro.

    Science.gov (United States)

    Tai, Joseph; Cheung, Susan; Wu, Matthew; Hasman, David

    2012-03-15

    Rosemary (Rosmarinus officinalis L.) is a popular culinary/medicinal herb. Recent studies have shown it has pharmacologic activities for cancer chemoprevention and therapy. This study evaluated the antiproliferation activity of rosemary extract (RE) against human ovarian cancer cells, and whether the extract and its three main active ingredients carnosol (CS), carnosic acid (CA) and rosmarinic acid (RA) can enhance the antiproliferation activity of cisplatin (CDDP). Our study showed that RE has significant antiproliferation activity on human ovarian cancer A2780 and its CDDP resistant daughter cell line A2780CP70, with IC(50) (50% inhibitory concentration) estimated at 1/1000 and 1/400 dilutions respectively. RE enhanced the antiproliferation effect with CDDP on both A2780 and A2780CP70 cells. A2780 cells were consistently more sensitive to CS, CA, and RA than A2780CP70 cells between 2.5 and 20μg/ml. CS and RA also showed synergistic antiproliferation effect with CDDP on A2780 cells at some concentrations. RE treated by ultrafiltration, dialysis, and removal of phenolics lost the antiproliferation activity suggested that the activity resides in phenolics with MW<1000Da. Apoptosis array study of A2780 cells treated with RE showed that the expression of a number of genes regulating apoptosis were modulated by the treatment. This study showed that RE inhibited the proliferation of ovarian cancer cell lines by affecting the cell cycle at multiple phases. It induced apoptosis by modifying the expression of multiple genes regulating apoptosis, and holds potential as an adjunct to cancer chemotherapy.

  14. 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

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

    Science.gov (United States)

    2014-12-23

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

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

    OpenAIRE

    Møller Pål

    2004-01-01

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

  17. Niosome Encapsulation of Curcumin: Characterization and Cytotoxic Effect on Ovarian Cancer Cells

    Directory of Open Access Journals (Sweden)

    Ying-Qi Xu

    2016-01-01

    Full Text Available Curcumin, a natural chemical compound found in Curcuma longa, has been applied in multiple medicinal areas from antibiotic to antitumor treatment. However, the chemical structure of curcumin results in poor stability, low solubility, and rapid degradation in vivo, hindering its clinical utilization. To address these issues, we have developed a novel niosome system composed of nonionic surfactants: Span 80, Tween 80, and Poloxamer 188. Curcumin was encapsulated in the niosomes with a high entrapment efficiency of 92.3±0.4%. This system provided controlled release of curcumin, thereby improving its therapeutic capability. Dynamic dialysis was conducted to evaluate the in vitro drug release of curcumin-niosomes. Curcumin-niosomes exhibited enhanced cytotoxic activity and apoptotic rate against ovarian cancer A2780 cells compared with freely dispersed curcumin. These results demonstrate that the curcumin-niosome system is a promising strategy for the delivery of curcumin and ovarian cancer therapy.

  18. Function of hypothalamic-hypophyseal-ovarian system in radiation treatment of patients with cervical cancer

    Energy Technology Data Exchange (ETDEWEB)

    Modnikov, O.P. (Kirgizskij Nauchno-Issledovatel' skij Inst. Onkologii i Radiologii, Frunze (USSR))

    1984-08-01

    Radioimmunoassay of the hypothalamic-hypophyseal-ovarian interrelationships was performed in 87 patients with cervical cancer and 37 practically healthy women. The basal level of the follicle-stimulating hormone (ESH), luteinizing hormone (LH) and estradiol as well as their response to the administration of the releasing factor of the hypothalamus (luliberin) were studied. Some disorders that manifested themselves in the decreased level of estradiol, were established in the patients with cervical cancer even before irradiation. Concomitant radiation therapy resulted in pronounced changes in the activities of the hypothalamic-hypophyseal-ovarian system that manifested themselves in the lowered rate of LH increment in response to the administration of luliberin and the absence of estradiol response to the load. These changes persisted long after the termination of concomitant radiation therapy.

  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...... 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...

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

    Science.gov (United States)

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

    2017-03-22

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Ke Wang

    2012-03-01

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

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

    Directory of Open Access Journals (Sweden)

    van der Burg SH

    2005-09-01

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

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    陈颖; 郑华川; 杨雪飞; 孙丽梅; 辛彦

    2004-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Zagouri F

    2015-08-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

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

    Science.gov (United States)

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Karina Biskup

    2014-01-01

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

  11. Do We Know What Causes Ovarian Cancer?

    Science.gov (United States)

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

  12. Mutant p53 promotes ovarian cancer cell adhesion to mesothelial cells via integrin β4 and Akt signals.

    Science.gov (United States)

    Lee, Jong-Gyu; Ahn, Ji-Hye; Jin Kim, Tae; Ho Lee, Jae; Choi, Jung-Hye

    2015-07-30

    Missense mutations in the TP53 gene resulting in the accumulation of mutant proteins are extremely common in advanced ovarian cancer, which is characterised by peritoneal metastasis. Attachment of cancer cells to the peritoneal mesothelium is regarded as an initial, key step for the metastatic spread of ovarian cancer. In the present study, we investigated the possible role of a p53 mutant in the mesothelial adhesion of ovarian cancer cells. We found that OVCAR-3 cells with the R248 TP53 mutation (p53(R248)) were more adhesive to mesothelial Met5A cells than were A2780 cells expressing wild-type p53. In addition, ectopic expression of p53(R248) in p53-null SKOV-3 cells significantly increased adhesion to Met5A cells. Knockdown of mutant p53 significantly compromised p53(R248)-induced cell adhesion to Met5A cells. Microarray analysis revealed that several adhesion-related genes, including integrin β4, were markedly up-regulated, and certain signalling pathways, including PI3K/Akt, were activated in p53(R248) transfectants of SKOV-3 cells. Inhibition of integrin β4 and Akt signalling using blocking antibody and the inhibitor LY294002, respectively, significantly attenuated p53(R248)-mediated ovarian cancer-mesothelial adhesion. These data suggest that the p53(R248) mutant endows ovarian cancer cells with increased adhesiveness and that integrin β4 and Akt signalling are associated with the mutation-enhanced ovarian cancer-mesothelial cell adhesion.

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

    NARCIS (Netherlands)

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

    2009-01-01

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

  14. 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

    particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. METHODS: Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15...

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

    Science.gov (United States)

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

    2016-11-01

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

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

    NARCIS (Netherlands)

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

    2008-01-01

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

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

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

    NARCIS (Netherlands)

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

    2011-01-01

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

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

    Science.gov (United States)

    2009-10-01

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

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

    Science.gov (United States)

    2013-07-01

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

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

    DEFF Research Database (Denmark)

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

    2007-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

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

  4. Combinatorial effect of non-steroidal anti-inflammatory drugs and NF-κB inhibitors in ovarian cancer therapy.

    Directory of Open Access Journals (Sweden)

    Luiz F Zerbini

    Full Text Available Several epidemiological studies have correlated the use of non-steroidal anti-inflammatory drugs (NSAID with reduced risk of ovarian cancer, the most lethal gynecological cancer, diagnosed usually in late stages of the disease. We have previously established that the pro-apoptotic cytokine melanoma differentiation associated gene-7/Interleukin-24 (mda-7/IL-24 is a crucial mediator of NSAID-induced apoptosis in prostate, breast, renal and stomach cancer cells. In this report we evaluated various structurally different NSAIDs for their efficacies to induce apoptosis and mda-7/IL-24 expression in ovarian cancer cells. While several NSAIDs induced apoptosis, Sulindac Sulfide and Diclofenac most potently induced apoptosis and reduced tumor growth. A combination of these agents results in a synergistic effect. Furthermore, mda-7/IL-24 induction by NSAIDs is essential for programmed cell death, since inhibition of mda-7/IL-24 by small interfering RNA abrogates apoptosis. mda-7/IL-24 activation leads to upregulation of growth arrest and DNA damage inducible (GADD 45 α and γ and JNK activation. The NF-κB family of transcription factors has been implicated in ovarian cancer development. We previously established NF-κB/IκB signaling as an essential step for cell survival in cancer cells and hypothesized that targeting NF-κB could potentiate NSAID-mediated apoptosis induction in ovarian cancer cells. Indeed, combining NSAID treatment with NF-κB inhibitors led to enhanced apoptosis induction. Our results indicate that inhibition of NF-κB in combination with activation of mda-7/IL-24 expression may lead to a new combinatorial therapy for ovarian cancer.

  5. PEA-15 Induces Autophagy in Human Ovarian Cancer Cells and is Associated with Prolonged Overall Survival

    OpenAIRE

    Bartholomeusz, Chandra; Rosen, Daniel; Wei, Caimiao; Kazansky, Anna; Yamasaki, Fumiyuki; Takahashi, Takeshi; Itamochi, Hiroaki; KONDO, Seiji; Liu, Jinsong; Ueno, Naoto T

    2008-01-01

    Phospho-enriched protein in astrocytes (PEA-15) is a 15-kDa phosphoprotein that slows cell proliferation by binding to and sequestering extracellular signal-regulated kinase (ERK) in the cytoplasm, thereby inhibiting ERK-dependent transcription and proliferation. In previous studies of E1A human gene therapy for ovarian cancer, we discovered that PEA-15 induced the antitumor effect of E1A by sequestering activated ERK in the cytoplasm of cancer cells. Here, we investigated the role of PEA-15 ...

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

    Science.gov (United States)

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

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

    Science.gov (United States)

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

  8. 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

  9. 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....

  10. 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.

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

    DEFF Research Database (Denmark)

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

    2009-01-01

    BACKGROUND: Several reproductive and hormonal factors are known to be associated with ovarian cancer risk in the general population, including parity and oral contraceptive (OC) use. However, their effect on ovarian cancer risk for BRCA1 and BRCA2 mutation carriers has only been investigated...... in a small number of studies. METHODS: We used data on 2,281 BRCA1 carriers and 1,038 BRCA2 carriers from the International BRCA1/2 Carrier Cohort Study to evaluate the effect of reproductive and hormonal factors on ovarian cancer risk for mutation carriers. Data were analyzed within a weighted Cox...... proportional hazards framework. RESULTS: There were no significant differences in the risk of ovarian cancer between parous and nulliparous carriers. For parous BRCA1 mutation carriers, the risk of ovarian cancer was reduced with each additional full-term pregnancy (P trend = 0.002). BRCA1 carriers who had...

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

    Science.gov (United States)

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

    2002-10-01

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

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

    Directory of Open Access Journals (Sweden)

    Judith Ann Ebbert

    2015-08-01

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

  14. Loss of HSulf-1 expression enhances tumorigenicity by inhibiting Bim expression in ovarian cancer.

    Science.gov (United States)

    He, Xiaoping; Khurana, Ashwani; Roy, Debarshi; Kaufmann, Scott; Shridhar, Viji

    2014-10-15

    The expression of human Sulfatase1 (HSulf-1) is downregulated in the majority of primary ovarian cancer tumors, but the functional consequence of this downregulation remains unclear. Using two different shRNAs (Sh1 and Sh2), HSulf-1 expression was stably downregulated in ovarian cancer OV202 cells. We found that HSulf-1-deficient OV202 Sh1 and Sh2 cells formed colonies in soft agar. In contrast, nontargeting control (NTC) shRNA-transduced OV202 cells did not form any colonies. Moreover, subcutaneous injection of OV202 HSulf-1-deficient cells resulted in tumor formation in nude mice, whereas OV202 NTC cells did not. Also, ectopic expression of HSulf-1 in ovarian cancer SKOV3 cells significantly suppressed tumor growth in nude mice. Here, we show that HSulf-1-deficient OV202 cells have markedly decreased expression of proapoptotic Bim protein, which can be rescued by restoring HSulf-1 expression in OV202 Sh1 cells. Enhanced expression of HSulf-1 in HSulf-1-deficient SKOV3 cells resulted in increased Bim expression. Decreased Bim levels after loss of HSulf-1 were due to increased p-ERK, because inhibition of ERK activity with PD98059 resulted in increased Bim expression. However, treatment with a PI3 kinase/AKT inhibitor, LY294002, failed to show any change in Bim protein level. Importantly, rescuing Bim expression in HSulf-1 knockdown cells significantly retarded tumor growth in nude mice. Collectively, these results suggest that loss of HSulf-1 expression promotes tumorigenicity in ovarian cancer through regulating Bim expression.

  15. Transforming growth factor-β stimulates human ovarian cancer cell migration by up-regulating connexin43 expression via Smad2/3 signaling.

    Science.gov (United States)

    Qiu, Xin; Cheng, Jung-Chien; Zhao, Jianfang; Chang, Hsun-Ming; Leung, Peter C K

    2015-10-01

    Reduced connexin43 (Cx43) expression is frequently detected in different types of human cancer. Cx43 has been shown to regulate cancer cell migration in a cell-type dependent manner. In both primary and recurrent human ovarian cancer, overexpression of TGF-β ligand and its receptors have been detected. TGF-β can regulate Cx43 expression in other cell types and stimulate human ovarian cancer cell migration. However, whether Cx43 can be regulated by TGF-β and is involved in TGF-β-stimulated cell migration in human ovarian cancer cells remain unknown. In this study, we demonstrate that TGF-β up-regulates Cx43 in two human ovarian cancer cell lines, SKOV3 and OVCAR4. The stimulatory effect of TGF-β on Cx43 expression is blocked by inhibition of TGF-β receptor. Treatment with TGF-β activates Smad2 and Smad3 signaling pathways in both ovarian cancer cell lines. In addition, siRNA-mediated knockdown of Smad2 or Smd3 abolishes TGF-β-induced up-regulation of Cx43 expression. Moreover, knockdown of Cx43 attenuates TGF-β-stimulated cell migration. This study demonstrates an important role for Cx43 in mediating the effects of TGF-β on human ovarian cancer cell migration.

  16. Sp1-CD147 positive feedback loop promotes the invasion ability of ovarian cancer.

    Science.gov (United States)

    Zhao, Jing; Ye, Wei; Wu, Juan; Liu, Lijuan; Yang, Lina; Gao, Lu; Chen, Biliang; Zhang, Fanglin; Yang, Hong; Li, Yu

    2015-07-01

    CD147 is a novel cancer biomarker that has been confirmed to be overexpressed in ovarian carcinoma, which is significantly associated with poor prognosis. Although the Sp1 protein regulates the expression level of CD147, it remains unclear whether Sp1 phosphorylation plays a role in this regulation. A dual-luciferase assay revealed that T453 and T739 mutations decreased the activity of Sp1 binding to the promoter of CD147, followed by a decrease in CD147 mRNA and protein expression. Western blot analysis showed that CD147 promoted Sp1 phosphorylation at T453 and T739 through the PI3K/AKT and MAPK/ERK pathways. In addition, blocking the Sp1-CD147 positive feedback loop reduced the invasion ability of HO-8910pm cells. Immunohistochemical staining showed that the components of the feedback loop were overexpressed in ovarian cancer tissues. The correlation analysis revealed a significant correlation between phospho-Sp1 (T453), phospho-Sp1 (T739) and CD147 expression levels, with correlation coefficients of r=0.477 and r=0.461, respectively. Collectively, our results suggest that a Sp1-CD147 positive feedback loop plays a critical role in the invasion ability of ovarian cancer cells.

  17. Dietary Cadmium Intake and Risk of Breast, Endometrial and Ovarian Cancer in Danish Postmenopausal Women: A Prospective Cohort Study

    OpenAIRE

    2014-01-01

    Purpose Cadmium is a human lung carcinogen and possesses estrogen-like activity. This combination of carcinogenic and estrogenic activity makes cadmium a contaminant of high concern for hormone-related cancers. Diet and smoking are the main sources of cadmium exposure. The aim of this study was to investigate the association between dietary cadmium intake and risk of breast, endometrial and ovarian cancer in Danish postmenopausal woman. Methods We estimated dietary cadmium intake in the Diet,...

  18. Prognostic value of plasma soluble urokinase plasminogen activator receptor (suPAR) in Danish patients with recurrent epithelial ovarian cancer (REOC)

    DEFF Research Database (Denmark)

    Begum, Farah Diba; Høgdall, Estrid V S; Riisbo, Rikke

    2006-01-01

    The level of the soluble urokinase plasminogen activator receptor (suPAR) is elevated in tumour tissue from several types of cancer. This is the first study aiming to predict the prognosis for survival by the use of a pre-chemotherapeutic plasma suPAR value in 71 patients with recurrent epithelial...

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2010-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-05-09

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

  3. Chemomodulatory effects ofIchnocarpus frutescens R. Br against 4-vinylcyclohexane induced ovarian cancer in swiss albino mice

    Institute of Scientific and Technical Information of China (English)

    Thangarajan Starlin; Perumal Sathiyanathan; Chinthamony Arul Raj; Paramasivam Ragavendran; Balasubramanian Vidya; Martin Sunitha

    2013-01-01

    Objective:To evaluate the protective effect ofIchnocarpus frutescens(I. frutescens)R.Br against 4-vinylcyclohexane induced ovarian cancer inSwiss albino mice.Method:The ovarian cancer was induced by4-vinylcyclohexane which was given to28-day-old mice in corn oil, intra peritoneally, at2.7 mmol/kg body weight/day for30 d.After that serum and tissue were isolated. Enzymatic antioxidants, non-enzymatic antioxidants, lipid peroxidationassessed in liver and ovary homogenate.Metabolites, marker enzymes were analyzed in serum.Tissue was examined histopathology examination.Result:The levels of urea, creatinine, marker enzymes and lipid peroxidation were significantly increased in ovarian cancer induced mice when compared to control group whereas, levels of uric acid, enzymatic and non-enzymatic antioxidants were decreased in cancer induced mice when compared with control mice.From these parameters were brought back to near normal in ethanolic extract ofI. frutescens treated animals.The above results were further confirmed by histopathological examination which shows marked edema of lamina propria occurred in cancer induced animals whereas no alterations in ethanolic extract of I. frutescens and cisplatin treated groups. Conclusion:This present study was evaluated that the ethanolic extracts ofI. frutescens have effective anticancer activity against4-vinylcyclohexane induced ovarian cancer.

  4. 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.

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

    NARCIS (Netherlands)

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

    2012-01-01

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

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

    DEFF Research Database (Denmark)

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

    2007-01-01

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

  7. Collagen I but not Matrigel matrices provide an MMP-dependent barrier to ovarian cancer cell penetration

    Directory of Open Access Journals (Sweden)

    Brown Theodore J

    2008-08-01

    Full Text Available Abstract Background The invasive potential of cancer cells is usually assessed in vitro using Matrigel as a surrogate basement membrane. Yet cancer cell interaction with collagen I matrices is critical, particularly for the peritoneal metastatic route undertaken by several cancer types including ovarian. Matrix metalloprotease (MMP activity is important to enable cells to overcome the barrier constraints imposed by basement membranes and stromal matrices in vivo. Our objective was to compare matrices reconstituted from collagen I and Matrigel as representative barriers for ovarian cancer cell invasion. Methods The requirement of MMP activity for ovarian cancer cell penetration of Matrigel and collagen matrices was assessed in 2D transwell and 3D spheroid culture systems. Results The broad range MMP inhibitor GM6001 completely prevented cell perforation of polymerised collagen I-coated transwell membranes. In contrast, GM6001 decreased ES-2 cell penetration of Matrigel by only ~30% and had no effect on HEY cell Matrigel penetration. In 3D culture, ovarian cancer cells grown as spheroids also migrated into surrounding Matrigel matrices despite MMP blockade. In contrast, MMP activity was required for invasion into 3D matrices of collagen I reconstituted from acid-soluble rat-tail collagen I, but not from pepsin-extracted collagen I (Vitrogen/Purecol, which lacks telopeptide regions. Conclusion Matrigel does not form representative barriers to ovarian cancer cells in either 2D or 3D culture systems. Our findings support the use of collagen I rather than Matrigel as a matrix barrier for invasion studies to better approximate critical interactions and events associated with peritoneal metastasis.

  8. Bevacizumab plus microtubule targeting agents in heavily pre-treated ovarian cancer patients: a retrospective study.

    Science.gov (United States)

    Asmane, Irène; Kurtz, Jean-Emmanuel; Bajard, Agathe; Guastalla, Jean-Paul; Meeus, Pierre; Tredan, Olivier; Labidi Galy, Intidhar; Moullet, Isabelle; Ardisson, Philippe; Vincent, Lionel; Coeffic, David; Dufresne, Armelle; Bergerat, Jean-Pierre; Ray-Coquard, Isabelle

    2011-10-01

    OBJECTIVES. As vascular endothelial growth factor (VEGF) is expressed in ovarian cancer, we assessed the efficacy and safety of bevacizumab (a monoclonal antibody targeting VEGF) plus microtubule targeting agents for heavily pre-treated ovarian carcinoma patients. METHODS. We retrospectively reviewed 43 patients with recurrent epithelial ovarian carcinoma. Combined treatment included bevacizumab with paclitaxel in 32 (74%), docetaxel in 10 (23%), and vinorelbine in one (2.3%) patients, respectively. RESULTS. The median number of combined treatment was six cycles (range 1-29). On RECIST criteria, the objective response rate (ORR) was 40% (16% CR and 24% PR). Clinical benefit (complete response [CR] plus partial response [PR] and stable disease [SD] lasting ≥ 3 months) was 74% (CI95%: 46.7-77%). Median duration of treatment and overall survival were 3.9 months (range 0.2-14.4 months) and 20.1 months (CI95%: 13.8-20.1) respectively. No toxic death was reported. Grade 3-4 toxicity occurred in 30% of patients. Gastrointestinal perforations and fistula occurred in 3 (7%) and 6 (14%) patients, respectively. CONCLUSION. Although being active in terms of ORR, bevacizumab plus microtubule targeting agents - mainly taxanes - leads to a high rate of gastro-intestinal perforations and fistula in heavily pre-treated ovarian carcinoma patients.

  9. The role of the tumor stroma in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Ben eDavidson

    2014-05-01

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

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

    Directory of Open Access Journals (Sweden)

    L. N. Lyubchenko

    2009-01-01

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

  11. Splicing variant of AIMP2 as an effective target against chemoresistant ovarian cancer

    Institute of Scientific and Technical Information of China (English)

    Jin Woo Choi; Jeong-Won Lee; Jun Ki Kim; Hye-Kyung Jeon; Jung-Joo Choi; Dae Gyu Kim; Byoung-Gie Kim

    2012-01-01

    Chemoresistance is a main cause for the failure of cancer management and intensive investigation is on-going to control chemoresistant (CR) cancers.Although NF-κB has been suggested as one of the potential targets to alleviate chemoresistance of epithelial ovarian cancer (EOC),direct targeting of NF-κB may result in an unexpected effect due to the complex regulatory network via NF-κB.Here we show that AIMP2-DX2,a splicing variant of tumor suppressor AIMP2,can be a therapeutic target to control CR EOC.AIMP2-DX2 was often highly expressed in CR EOC both in vitro and in vivo.AIMP2-DX2 compromised the tumor necrosis factor alpha-dependent pro-apoptotic activity of AIMP2 via the competitive inhibition of AIMP2 binding to TRAF2 that plays a pivotal role in the regulation of NF-κB.The direct delivery of siRNA against AIMP2-DX2 into abdominal metastatic tumors of ovarian cancer using a microneedle converged on microendoscopy significantly suppressed the growth rate of tumors.The treated cancer tissues showed an enhanced apoptosis and the decreased TRAF2 level.Thus,we suggest that the downregulation of AIMP2-DX2 can be a potent adjuvant therapeutic approach for CR EOC that resulted from an aberrant activity of NF-κB.

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

    Directory of Open Access Journals (Sweden)

    Matthew Schwede

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

  13. Chaetoglobosin K induces apoptosis and G2 cell cycle arrest through p53-dependent pathway in cisplatin-resistant ovarian cancer cells.

    Science.gov (United States)

    Li, Bo; Gao, Ying; Rankin, Gary O; Rojanasakul, Yon; Cutler, Stephen J; Tu, Youying; Chen, Yi Charlie

    2015-01-28

    Adverse side effects and acquired resistance to conventional platinum based chemotherapy have become major impediments in ovarian cancer treatment, and drive the development of more selective anticancer drugs. Chaetoglobosin K (ChK) was shown to have a more potent growth inhibitory effect than cisplatin on two cisplatin-resistant ovarian cancer cell lines, OVCAR-3 and A2780/CP70, and was less cytotoxic to a normal ovarian cell line, IOSE-364, than to the cancer cell lines. Hoechst 33342 staining and Flow cytometry analysis indicated that ChK induced preferential apoptosis and G2 cell cycle arrest in both ovarian cancer cells with respect to the normal ovarian cells. ChK induced apoptosis through a p53-dependent caspase-8 activation extrinsic pathway, and caused G2 cell cycle arrest via cyclin B1 by increasing p53 expression and p38 phosphorylation in OVCAR-3 and A2780/CP70 cells. DR5 and p21 might play an important role in determining the sensitivity of normal and malignant ovarian cells to ChK. Based on these results, ChK would be a potential compound for treating platinum-resistant ovarian cancer.

  14. Pegylated liposomal doxorubicin in ovarian cancer

    OpenAIRE

    Matei, Daniela

    2009-01-01

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

  15. Lifestyle changes and the risk of developing endometrial and ovarian cancers: opportunities for prevention and management

    Directory of Open Access Journals (Sweden)

    Beavis AL

    2016-05-01

    Full Text Available Anna L Beavis,1,* Anna Jo Bodurtha Smith,2,* Amanda Nickles Fader1 1Department of Gynecology and Obstetrics, The Kelly Gynecologic Oncology Service, Johns Hopkins Medicine, Baltimore, MD, 2Harvard Medical School, Boston, MA, USA *These authors contributed equally to this work Abstract: Modifiable lifestyle factors, such as obesity, lack of physical activity, and smoking, contribute greatly to cancer and chronic disease morbidity and mortality worldwide. This review appraises recent evidence on modifiable lifestyle factors in the prevention of endometrial cancer (EC and ovarian cancer (OC as well as new evidence for lifestyle management of EC and OC survivors. For EC, obesity continues to be the strongest risk factor, while new evidence suggests that physical activity, oral contraceptive pills, and bariatric surgery may be protective against EC. Other medications, such as metformin and nonsteroidal anti-inflammatory drugs, may be protective, and interventional research is ongoing. For OC, we find increasing evidence to support the hypothesis that obesity and hormone replacement therapy increase the risk of developing OC. Oral contraceptive pills are protective against OC but are underutilized. Dietary factors such as the Mediterranean diet and alcohol consumption do not seem to affect the risk of either OC or EC. For EC and OC survivors, physical activity and weight loss are associated with improved quality of life. Small interventional trials show promise in increasing physical activity and weight maintenance for EC and OC survivors, although the impact on long-term health, including cancer recurrence and overall mortality, is unknown. Women’s health providers should integrate counseling about these modifiable lifestyle factors into both the discussion of prevention for all women and the management of survivors of gynecologic cancers. Keywords: lifestyle, prevention, endometrial cancer, ovarian cancer, gynecologic cancer, obesity

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

    Science.gov (United States)

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

    2017-02-28

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2015-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Sang Young

    1999-12-01

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

  19. Obesity Exposure Across the Lifespan on Ovarian Cancer Pathogenesis

    Science.gov (United States)

    2014-06-01

    genes ( Supplemental Tables 1 and 2). Genes that were down-regulated included the prolactin receptor (3.6 fold) and apolipoprotein B mRNA editing...3.3 fold), carnitine /acylcarnitine translocase (3.2 fold), low density lipoprotein receptor-related protein 8 (apolipoprotein e receptor) (3.7 fold...upregulated in ovarian tumors from overweight/obese women such as mitogen-activated protein kinase 1, phospholipid scramblase 1, carnitine

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

    Science.gov (United States)

    Weiderpass, Elisabete; Tyczynski, Jerzy E

    2015-12-01

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