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Sample records for progressive advanced ovarian

  1. The prediction of progression-free and overall survival in women with an advanced stage of epithelial ovarian carcinoma.

    Science.gov (United States)

    Gerestein, C G; Eijkemans, M J C; de Jong, D; van der Burg, M E L; Dykgraaf, R H M; Kooi, G S; Baalbergen, A; Burger, C W; Ansink, A C

    2009-02-01

    Prognosis in women with ovarian cancer mainly depends on International Federation of Gynecology and Obstetrics stage and the ability to perform optimal cytoreductive surgery. Since ovarian cancer has a heterogeneous presentation and clinical course, predicting progression-free survival (PFS) and overall survival (OS) in the individual patient is difficult. The objective of this study was to determine predictors of PFS and OS in women with advanced stage epithelial ovarian cancer (EOC) after primary cytoreductive surgery and first-line platinum-based chemotherapy. Retrospective observational study. Two teaching hospitals and one university hospital in the south-western part of the Netherlands. Women with advanced stage EOC. All women who underwent primary cytoreductive surgery for advanced stage EOC followed by first-line platinum-based chemotherapy between January 1998 and October 2004 were identified. To investigate independent predictors of PFS and OS, a Cox' proportional hazard model was used. Nomograms were generated with the identified predictive parameters. The primary outcome measure was OS and the secondary outcome measures were response and PFS. A total of 118 women entered the study protocol. Median PFS and OS were 15 and 44 months, respectively. Preoperative platelet count (P = 0.007), and residual disease statistic of 0.63. Predictive parameters for OS were preoperative haemoglobin serum concentration (P = 0.012), preoperative platelet counts (P = 0.031) and residual disease statistic of 0.67. PFS could be predicted by postoperative residual disease and preoperative platelet counts, whereas residual disease, preoperative platelet counts and preoperative haemoglobin serum concentration were predictive for OS. The proposed nomograms need to be externally validated.

  2. 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.

  3. Neoadjuvant Chemotherapy for Advanced Epithelial Ovarian Cancer

    International Nuclear Information System (INIS)

    Avendano Juan; Buitrago, Giancarlo; Ramos, Pedro; Suescun Oscar

    2010-01-01

    Objective: To describe the experience at the National Cancer Institute (NCI) on the use of neoadjuvant chemotherapy as primary treatment for epithelial ovarian cancer among patients in stages IIIC and IV. Methods: We conducted a descriptive retrospective study (case series type) of patients diagnosed with epithelial ovarian cancer in stages IIIC and IV, treated at the NCI from January 1, 2003 to December 31,2006, who underwent neoadjuvant chemotherapy as primary treatment. Demographic characteristics and clinical outcomes are described. Results: Seventeen patients who fulfilled the above mentioned criteria were selected. Once neoadjuvant chemotherapy ended, 5 patients (29.4%) achieved complete or partial clinical response; 4 (23.8%) remained in stable condition, and 8 (47.6%) showed signs of progressive illness. Interval debulking surgery was performed on objective response patients. Maximum cytoreduction was achieved in 5 patients (100%); first relapse was reported at month 18 of follow-up; 2 disease-free survivors were identified in December, 2007; 8 (49%) reported some degree of non-severe chemotherapy-related toxicity. No mortality was related to chemotherapy, no post surgical complications were observed and no patient required advanced support management. Conclusions: Neoadjuvant chemotherapy, followed by optimal interval debulking surgery among selected patients, can be an alternative treatment for advanced epithelial ovarian cancer among women with irresecability or the critically ill. Further studies with improved design are required to confirm these findings.

  4. Plasma and ovarian tissue sphingolipids profiling in patients with advanced ovarian cancer.

    Science.gov (United States)

    Knapp, Paweł; Bodnar, Lubomir; Błachnio-Zabielska, Agnieszka; Świderska, Magdalena; Chabowski, Adrian

    2017-10-01

    The role of lipids in carcinogenesis through induction of abnormal cell lines in the human body is currently undisputable. Based on the literature, bioactive sphingolipids play an essential role in the development and progression of cancer and are involved in the metastatic process. The aim of this study was to determine the concentration of selected sphingolipids in patients with advanced ovarian cancer (AOC, FIGO III/IV, high grade ovarian cancer). Seventy-four patients with ovarian cancer were enrolled. Plasma concentrations of C16-Cer, C18:1-Cer and C18-Cer were assessed by LC/MS/MS. The content of tissue sphingolipids was measured using a UHPLC/MS/MS. Plasma concentration of 3 ceramides: C16-Cer, C18:1-Cer and C18-Cer was significantly elevated in women with advanced ovarian cancer compared to control group (P=0.031; 0.022; 0.020; respectively). There were increases in concentration of 5 ceramides: C16-Cer, C18:1-Cer, C18-Cer, C24:1-Cer, C24-Cer (P=0.025; 0.049; 0.032; 0.005; 0.013, respectively) and S1P (P=0.004) in ovarian tissue of women with advanced ovarian cancer compared to healthy individuals. Importantly, significantly higher risk of ovarian cancer when the plasma concentration of C16-Cer>311.88ng/100μl (AUC: 0.76, P=0.0261); C18:1-Cer>4.75ng/100μl (AUC: 0.77, P=0.0160) and C18-Cer>100.76ng/100μl (AUC:0.77, P=0.0136) was noticed. Bioactive sphingolipids play an essential role in the development and progression of cancer and they also take part in the process of metastasizing. This study suggests that some sphingolipids can be used as potential biomarkers of advanced ovarian cancer and that they can play an important role in the pathogenesis of this disease. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    2017-07-01

    cells and in transformed ovarian cells affected by obesity that lead to ovarian cancer initiation and progression. 15. SUBJECT TERMS Obesity, Ovarian...5 7. Participants & Other Collaborating Organizations...that lead to ovarian cancer initiation and progression. We also aim to identify secreted factors from adipose tissue that promote ovarian cancer

  6. Tumor angiogenesis in advanced stage ovarian carcinoma.

    Science.gov (United States)

    Hollingsworth, H C; Kohn, E C; Steinberg, S M; Rothenberg, M L; Merino, M J

    1995-07-01

    Tumor angiogenesis has been found to have prognostic significance in many tumor types for predicting an increased risk of metastasis. We assessed tumor vascularity in 43 cases of advanced stage (International Federation of Gynecologists and Obstetricians stages III and IV) ovarian cancer by using the highly specific endothelial cell marker CD34. Microvessel counts and stage were associated with disease-free survival and with overall survival by Kaplan-Meier analysis. The plots show that higher stage, higher average vessel count at 200x (200x avg) and 400x (400x avg) magnification and highest vessel count at 400x (400x high) magnification confer a worse prognosis for disease-free survival. Average vessel count of less than 16 (400x avg, P2 = 0.01) and less than 45 (200x avg, P2 = 0.026) suggested a better survival. Similarly, a high vessel count of less than 20 (400x high, P2 = 0.019) conferred a better survival as well. The plots suggest that higher stage, higher average vessel count at 200x and 400x, and highest vessel count at 200x and 400x show a trend to worse overall survival as well. With the Cox proportional hazards model, stage was the best predictor of overall survival, however, the average microvessel count at 400x was found to be the best predictor of disease-free survival. These results suggest that analysis of neovascularization in advanced stage ovarian cancer may be a useful prognostic factor.

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

    International Nuclear Information System (INIS)

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

    2013-01-01

    Ovarian cancer is one of the most lethal malignant gynecological tumors. More than 70% of patients with ovarian cancer are diagnosed at advanced stage. The 5-year survival in patients with advanced ovarian cancer is less than 30% because of the lack of effective biomarkers for diagnosis, prognosis, and personalized treatment. MicroRNA (miR) is a class of small noncoding RNAs that negatively regulate gene expression primarily through post-transcriptional repression. Many studies on tissue miR in ovarian cancer have been carried out and show great potential in clinical practice. However, tissue samples are not easily available because sampling causes injury. Researchers have started to focus on plasma/serum miR, assuming that blood samples may replace tissue samples in miR research in the future. Plasma/serum miR research is still in its early stages. Studies on its function in the early diagnosis of ovarian cancer have achieved some progress, but plasma/serum miR profiling for prognosis and personalized treatment of ovarian cancer remains unknown. A thorough understanding of the function of plasma/serum miR in ovarian cancer will facilitate early diagnosis and improve treatment for ovarian cancer

  8. Termination of Pregnancy in a Patient with Advanced Ovarian Cancer

    OpenAIRE

    Suna Özdemir; Çetin Çelik; Kazım Gezginç; Hasan Esen

    2010-01-01

    Ovarian cancer during pregnancy is a rare entity and the management of the disease can be challenging for the patient and the clinician. In this case, we report a case of advanced ovarian carcinoma diagnosed during pregnancy, which was managed with termination of pregnancy and chemotheraphy. The patient was underwent exploratory laparatomy including the right ovarian cystectomy, omentectomy, appendectomy, pelvic and para-aortic lymphadenectomy after frozen section of borderline serous cystade...

  9. Optimal primary surgical treatment for advanced epithelial ovarian cancer.

    Science.gov (United States)

    Elattar, Ahmed; Bryant, Andrew; Winter-Roach, Brett A; Hatem, Mohamed; Naik, Raj

    2011-08-10

    -based chemotherapy. We only included studies that defined optimal cytoreduction as surgery leading to residual tumours with a maximum diameter of any threshold up to 2 cm. Two review authors independently abstracted data and assessed risk of bias. Where possible, the data were synthesised in a meta-analysis. There were no RCTs or prospective non-RCTs identified that were designed to evaluate the effectiveness of surgery when performed as a primary procedure in advanced stage ovarian cancer.We found 11 retrospective studies that included a multivariate analysis that met our inclusion criteria. Analyses showed the prognostic importance of complete cytoreduction, where the residual disease was microscopic that is no visible disease, as overall (OS) and progression-free survival (PFS) were significantly prolonged in these groups of women. PFS was not reported in all of the studies but was sufficiently documented to allow firm conclusions to be drawn.When we compared suboptimal (> 1 cm) versus optimal ( 2 cm and factors, selection bias was still likely to be of particular concern.Adverse events, quality of life (QoL) and cost-effectiveness were not reported by treatment arm or to a satisfactory level in any of the studies. During primary surgery for advanced stage epithelial ovarian cancer all attempts should be made to achieve complete cytoreduction. When this is not achievable, the surgical goal should be optimal (related and disease-related factors that are associated with the improved survival in these groups of women. The findings of this review that women with residual disease 1 cm should prompt the surgical community to retain this category and consider re-defining it as 'near optimal' cytoreduction, reserving the term 'suboptimal' cytoreduction to cases where the residual disease is > 1 cm (optimal/near optimal/suboptimal instead of complete/optimal/suboptimal).

  10. Interval debulking surgery in advanced epithelial ovarian cancer.

    Science.gov (United States)

    Pecorelli, Sergio; Odicino, Franco; Favalli, Giuseppe

    2002-08-01

    Cytoreductive surgery and chemotherapy are the mainstay for the treatment of advanced epithelial ovarian cancer. In order to minimize the tumour burden before chemotherapy, cytoreductive surgery is usually performed first. The importance of the amount of residual disease as the main prognostic factor for patients suffering from advanced disease has been almost universally accepted even in the absence of prospective randomized trials addressing the benefit of cytoreductive surgery. In the last decade, the value of debulking surgery after induction chemotherapy - interval debulking surgery, IDS - has been widely debated, especially after the completion of a prospective randomized study from the EORTC addressing the introduction of a surgical procedure with debulking intent preceded and followed by cytoreductive chemotherapy. The rationale of such a strategy in the context of the primary treatment of advanced ovarian cancer lies in a higher cytoreductibility to the 'optimal' status forwarded, and possibly facilitated, by chemotherapy. The results demonstrated a prolongation of both progression-free survival and median survival in favour of patients randomized to IDS (5 and 6 months, respectively). Multivariate analysis revealed IDS to be an independent prognostic factor which reduced the risk of death by 33% at 3 years and by 48% in subsequent re-evaluation after more than 6 years of observation. Despite the above, results have been questioned by many, leading the GOG to perform a similar study which has been concluded very recently. Nevertheless, the main concern regarding the application of IDS in all instances relates to the morbidity of two major surgical procedures integrated within a short period during which cytotoxic chemotherapy is also administered. Neoadjuvant chemotherapy has been recently proposed to avoid a non-useful surgical procedure in patients considered 'optimally unresectable' after diagnosis of advanced ovarian cancer. Whether or not this newer

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

    International Nuclear Information System (INIS)

    Chung, Hyun Hoon; Lee, Maria; Kim, Hee-Seung; Kim, Jae-Weon; Park, Noh-Hyun; Song, Yong Sang; Cheon, Gi Jeong

    2017-01-01

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

  12. 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...

  13. 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...

  14. Recent technological advances in using mouse models to study ovarian cancer.

    Science.gov (United States)

    House, Carrie Danielle; Hernandez, Lidia; Annunziata, Christina Messineo

    2014-01-01

    Serous epithelial ovarian cancer (SEOC) is the most lethal gynecological cancer in the United States with disease recurrence being the major cause of morbidity and mortality. Despite recent advances in our understanding of the molecular mechanisms responsible for the development of SEOC, the survival rate for women with this disease has remained relatively unchanged in the last two decades. Preclinical mouse models of ovarian cancer, including xenograft, syngeneic, and genetically engineered mice, have been developed to provide a mechanism for studying the development and progression of SEOC. Such models strive to increase our understanding of the etiology and dissemination of ovarian cancer in order to overcome barriers to early detection and resistance to standard chemotherapy. Although there is not a single model that is most suitable for studying ovarian cancer, improvements have led to current models that more closely mimic human disease in their genotype and phenotype. Other advances in the field, such as live animal imaging techniques, allow effective monitoring of the microenvironment and therapeutic efficacy. New and improved preclinical mouse models, combined with technological advances to study such models, will undoubtedly render success of future human clinical trials for patients with SEOC.

  15. Termination of Pregnancy in a Patient with Advanced Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Suna Özdemir

    2010-04-01

    Full Text Available Ovarian cancer during pregnancy is a rare entity and the management of the disease can be challenging for the patient and the clinician. In this case, we report a case of advanced ovarian carcinoma diagnosed during pregnancy, which was managed with termination of pregnancy and chemotheraphy. The patient was underwent exploratory laparatomy including the right ovarian cystectomy, omentectomy, appendectomy, pelvic and para-aortic lymphadenectomy after frozen section of borderline serous cystadenocarcinoma at the 14 week of gestation. After final histopathology, the patient was staged as having FIGO stage IIIC disease. The pregnancy was termineted with the decision of patient and her family. The patient was treated with chemotheraphy.

  16. Progress in advanced accelerator concepts

    International Nuclear Information System (INIS)

    Sessler, A.M.

    1994-08-01

    A review is given of recent progress in this field, drawing heavily upon material presented at the Workshop on Advanced Accelerator Concepts, The Abbey, June 12--18, 1994. Attention is addressed to (1) plasma based concepts, (2) photo-cathodes, (3) radio frequency sources and Two-Beam Accelerators, (4) near and far-field schemes (including collective accelerators), (5) beam handling and conditioning, and (6) exotic collider concepts (such as photon colliders and muon colliders)

  17. Overexpression of inhibitor of DNA-binding (ID)-1 protein related to angiogenesis in tumor advancement of ovarian cancers

    International Nuclear Information System (INIS)

    Maw, Min Khine; Fujimoto, Jiro; Tamaya, Teruhiko

    2009-01-01

    The inhibitor of DNA-binding (ID) has been involved in cell cycle regulation, apoptosis and angiogenesis. This prompted us to study ID functions in tumor advancement of ovarian cancers. Sixty patients underwent surgery for ovarian cancers. In ovarian cancers, the levels of ID-1, ID-2 and ID-3 mRNAs were determined by real-time reverse transcription-polymerase chain reaction. The histoscore with the localization of ID-1 was determined by immunohistochemistry. Patient prognosis was analyzed with a 36-month survival rate. Microvessel counts were determined by immunohistochemistry for CD34 and factor VIII-related antigen. ID-1 histoscores and mRNA levels both significantly (p < 0.001) increased in ovarian cancers according to clinical stage, regardless of histopathological type. Furthermore, 30 patients with high ID-1 expression had a lower survival rate (53%) compared to patients with low ID-1 expression (80%). ID-1 histoscores and mRNA levels significantly (p < 0.0001) correlated with microvessel counts in ovarian cancers. ID-1 increased in ovarian cancer cells during tumor progression. Moreover, ID-1 expression levels correlated with microvessel counts. Therefore, ID-1 might work on tumor advancement via angiogenesis and is considered to be a candidate for a prognostic indicator in ovarian cancers

  18. Integrated genomics of ovarian xenograft tumor progression and chemotherapy response

    International Nuclear Information System (INIS)

    Stuckey, Ashley; Brodsky, Alexander S; Fischer, Andrew; Miller, Daniel H; Hillenmeyer, Sara; Kim, Kyu K; Ritz, Anna; Singh, Rakesh K; Raphael, Benjamin J; Brard, Laurent

    2011-01-01

    Ovarian cancer is the most deadly gynecological cancer with a very poor prognosis. Xenograft mouse models have proven to be one very useful tool in testing candidate therapeutic agents and gene function in vivo. In this study we identify genes and gene networks important for the efficacy of a pre-clinical anti-tumor therapeutic, MT19c. In order to understand how ovarian xenograft tumors may be growing and responding to anti-tumor therapeutics, we used genome-wide mRNA expression and DNA copy number measurements to identify key genes and pathways that may be critical for SKOV-3 xenograft tumor progression. We compared SKOV-3 xenografts treated with the ergocalciferol derived, MT19c, to untreated tumors collected at multiple time points. Cell viability assays were used to test the function of the PPARγ agonist, Rosiglitazone, on SKOV-3 cell growth. These data indicate that a number of known survival and growth pathways including Notch signaling and general apoptosis factors are differentially expressed in treated vs. untreated xenografts. As tumors grow, cell cycle and DNA replication genes show increased expression, consistent with faster growth. The steroid nuclear receptor, PPARγ, was significantly up-regulated in MT19c treated xenografts. Surprisingly, stimulation of PPARγ with Rosiglitazone reduced the efficacy of MT19c and cisplatin suggesting that PPARγ is regulating a survival pathway in SKOV-3 cells. To identify which genes may be important for tumor growth and treatment response, we observed that MT19c down-regulates some high copy number genes and stimulates expression of some low copy number genes suggesting that these genes are particularly important for SKOV-3 xenograft growth and survival. We have characterized the time dependent responses of ovarian xenograft tumors to the vitamin D analog, MT19c. Our results suggest that PPARγ promotes survival for some ovarian tumor cells. We propose that a combination of regulated expression and copy number

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-11-15

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

  20. Role of Diet Modulation and AMPK in Ovarian Cancer Progression and Outcome

    Science.gov (United States)

    2014-10-01

    and ovarian cancer. Recently some studies have suggested that low - fat dietary pattern may reduce the incidence of ovarian cancer. High energy and...energy metabolism using nature of diet (high vs low energy) focusing on AMPK as a central energy regulator in ovarian cancer progression using a...used in research (7.2% fat ; 61.6% carbohydrate ; 20.5% proteins). The nutritionally balanced HED consisted of 60% kilocalories from fat (35.7

  1. Palliative surgical approach in advanced nonresponsive mucinous ovarian cancer: A rare case report

    Directory of Open Access Journals (Sweden)

    Manika Agarwal

    2016-01-01

    Full Text Available Advanced mucinous ovarian cancer is a separate entity and has different biological behaviour. There is a wide range of therapeutic challenges and dilemmas in the management of these patients. The authors present a case of advanced ovarian mucinous cystadenocarcinoma with pseudomyxoma peritonei who had poor response to standard neoadjuvant chemotherapy. This case is highlighted to emphasize the challenges in the decision making for the management of advanced mucinous ovarian cancer.

  2. Dose-dense paclitaxel with carboplatin for advanced ovarian cancer: a feasible treatment alternative.

    Science.gov (United States)

    Glaze, Sarah; Teitelbaum, Lisa; Chu, Pamela; Ghatage, Prafull; Nation, Jill; Nelson, Gregg

    2013-01-01

    Epithelial ovarian cancer is the leading cause of death from gynaecologic cancers in the Western world. If possible, initial cytoreductive surgery is the treatment of choice, followed by adjuvant chemotherapy, usually with a platinum/taxane combination. Increased survival has been recently reported in women who were given adjuvant chemotherapy weekly rather than at three-week intervals, which has been the standard. At our centre, we have been treating patients with advanced ovarian cancer with a dose-dense protocol since March 2010. Treatment is given in an outpatient setting on days 1, 8, and 15 of a 21-day cycle for six cycles. Carboplatin for an AUC of 5 mg/mL/min and paclitaxel 80mg/m² are given on day 1, followed by paclitaxel 80mg/m² on days 8 and 15. Our objective was to determine whether this protocol is a feasible alternative treatment in our population and whether or not the toxicity profile is acceptable. We performed a chart review of 46 patients undergoing treatment with dose-dense chemotherapy for advanced ovarian cancer. Demographic information, patient characteristics, adverse events, and treatment endpoints were recorded. Sixty-one percent of women completed the six-cycle protocol as planned with minimal interruption, which is comparable to the only previously reported trial using this regimen. The most common side effects of treatment were fatigue, neuropathy, and neutropenia. Supplementation with regular magnesium and granulocyte colony-stimulating factor reduced delays. Dose-dense paclitaxel with carboplatin chemotherapy for the treatment of advanced ovarian cancer shows promise in terms of progression-free and overall survival. We have shown this protocol to be practical and feasible in our population.

  3. AT-406, an orally active antagonist of multiple inhibitor of apoptosis proteins, inhibits progression of human ovarian cancer.

    Science.gov (United States)

    Brunckhorst, Melissa K; Lerner, Dimitry; Wang, Shaomeng; Yu, Qin

    2012-07-01

    Ovarian carcinoma is the most deadly gynecological malignancy. Current chemotherapeutic drugs are only transiently effective and patients with advance disease often develop resistance despite significant initial responses. Mounting evidence suggests that anti-apoptotic proteins, including those of the inhibitor of apoptosis protein (IAP) family, play important roles in the chemoresistance. There has been a recent emergence of compounds that block the IAP functions. Here, we evaluated AT-406, a novel and orally active antagonist of multiple IAP proteins, in ovarian cancer cells as a single agent and in the combination with carboplatin for therapeutic efficacy and mechanism of action. We demonstrate that AT-406 has significant single agent activity in 60% of human ovarian cancer cell lines examined in vitro and inhibits ovarian cancer progression in vivo and that 3 out of 5 carboplatin-resistant cell lines are sensitive to AT-406, highlighting the therapeutic potential of AT-406 for patients with inherent or acquired platinum resistance. Additionally, our in vivo studies show that AT-406 enhances the carboplatin-induced ovarian cancer cell death and increases survival of the experimental mice, suggesting that AT-406 sensitizes the response of these cells to carboplatin. Mechanistically, we demonstrate that AT-406 induced apoptosis is correlated with its ability to down-regulate XIAP whereas AT-406 induces cIAP1 degradation in both AT-406 sensitive and resistance cell lines. Together, these results demonstrate, for the first time, the anti-ovarian cancer efficacy of AT-406 as a single agent and in the combination with carboplatin, suggesting that AT-406 has potential as a novel therapy for ovarian cancer patients, especially for patients exhibiting resistance to the platinum-based therapies.

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

    NARCIS (Netherlands)

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

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

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

    Directory of Open Access Journals (Sweden)

    Kathryn Mills

    2017-01-01

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

  6. A Fusogenic Oncolytic Herpes Simplex Virus for Therapy of Advanced Ovarian Cancer

    National Research Council Canada - National Science Library

    Zhang, Xiaoliu

    2004-01-01

    The tasks that were originally planned for the first year of this 3 year project are to demonstrate that the fusogenic oncolytic herpes simplex viruses are potent anti-tumor agents for advanced ovarian cancer...

  7. 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...

  8. 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...

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

    Science.gov (United States)

    Nikolaoul, Marinos; Stamenković, Srdjan; Stergiou, Christos; Skarleas, Christos; Torrens, Michael

    2015-01-01

    Brain metastases from epithelial ovarian cancer (EOC) are rare events. We present a rare case of single ovarian cancer metastasis to the brain treated with gamma-knife radiosurgery (GKRS). A 65-year-old woman with advanced EOC presented with severe neurologic symptoms. A single brain metastasis of 3.2 cm with surrounding edema in the left parietal lobe was detected by brain magnetic resonance imaging (MRI) scan during the work-up. The decision to perform GKRS was due to a surgical inaccessibility of intracranial lesion. Twelve weeks after the procedure, the MRI scan showed reduction in the diameter of brain metastasis and surrounding edema and the patient returned to good mental and motor performance.The patient survived for 22 months following treatment and died from a progressive intra-abdominal disease. Prognosis of ovarian cancer patients with brain metastases is generally poor regardless of treatment. Our case shows that GKRS as primary treatment modality for the control of ovarian cancer metastases to the brain was effective and can be considered as a treatment of choice if international selection criteria are followed.

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

    Directory of Open Access Journals (Sweden)

    Nikolaou Marinos

    2015-01-01

    Full Text Available Introduction. Brain metastases from epithelial ovarian cancer (EOC are rare events. We present a rare case of single ovarian cancer metastasis to the brain treated with gamma-knife radiosurgery (GKRS. Case Outline. A 65-year-old woman with advanced EOC presented with severe neurologic symptoms. A single brain metastasis of 3.2 cm with surrounding edema in the left parietal lobe was detected by brain magnetic resonance imaging (MRI scan during the work-up. The decision to perform GKRS was due to a surgical inaccessibility of intracranial lesion. Twelve weeks after the procedure, the MRI scan showed reduction in the diameter of brain metastasis and surrounding edema and the patient returned to good mental and motor performance. The patient survived for 22 months following treatment and died from a progressive intra-abdominal disease. Prognosis of ovarian cancer patients with brain metastases is generally poor regardless of treatment. Conclusion. Our case shows that GKRS as primary treatment modality for the control of ovarian cancer metastases to the brain was effective and can be considered as a treatment of choice if international selection criteria are followed.

  11. Mothering With Advanced Ovarian Cancer: "You've Got to Find That Little Thing That's Going to Make You Strong".

    Science.gov (United States)

    Arida, Janet A; Bressler, Toby; Moran, Samantha; DʼArpino, Sara; Carr, Alaina; Hagan, Teresa L

    2018-02-27

    Mothers with ovarian cancer are at risk of experiencing additional demands given their substantial symptom burden and accelerated disease progression. This study describes the experience of mothers with ovarian cancer, elucidating the interaction between their roles as mothers and patients with cancer. We conducted a secondary analysis of focus groups with women with advanced ovarian cancer. Using descriptive coding, we developed a coding framework based on emerging findings and group consensus. We then identified higher-order themes capturing the breadth of experiences described by mothers with ovarian cancer. Eight of the 13 participants discussed motherhood. The mean age of participants was 48.38 (SD, 7.17) years. All women were white (9/9), most had some college education (6/9), and the majority were married (5/9). Mean time since diagnosis was 7.43 (SD, 4.69) months; more than half of women (5/9) were currently receiving treatment. Themes and exemplar quotes reflected participants' evolving self-identities from healthy mother to cancer patient to woman mothering with cancer. Subthemes related to how motherhood was impacted by symptoms, demands of treatment, and the need to gain acceptance of living with cancer. The experience of motherhood impacts how women experience cancer and how they evolve as survivors. Similarly, cancer influences mothering. Healthcare providers should understand and address the needs of mothers with ovarian cancer. This study adds to the limited literature in this area and offers insight into the unique needs faced by women mothering while facing advanced cancer.

  12. Ovarian function’s role during cancer cachexia progression in the female mouse

    Science.gov (United States)

    Hetzler, Kimbell L.; Hardee, Justin P.; LaVoie, Holly A.; Murphy, E. Angela

    2017-01-01

    Cachexia is a debilitating condition that occurs with chronic disease, including cancer; our research has shown that some regulation of cancer cachexia progression is affected by sex differences. The ApcMin/+ mouse is genetically predisposed to develop intestinal tumors; IL-6 signaling and hypogonadism are associated with cachexia severity in the male. This relationship in the female warrants further investigation, as we have shown that the ability of IL-6 to induce cachexia differs between the sexes. Since ovarian reproductive function relies on a complex system of endocrine signaling to affect whole body homeostasis, we examined the relationship between ovarian reproductive function and progression of cancer cachexia in the female ApcMin/+ mouse. Our study of ovarian reproductive function in female ApcMin/+ mice showed disease-related cessation of estrous cycling (acyclicity) in 38% of mice. Acyclicity, including morphological and functional losses and enhanced muscle inflammatory gene expression, was associated with severe cachexia. Interestingly, ovariectomy rescued body weight and muscle mass and function but increased muscle sensitivity to systemic IL-6 overexpression. In conclusion, our results provide evidence for a relationship between ovarian reproductive function and cachexia progression in female ApcMin/+ mice. PMID:28292759

  13. Ovarian function's role during cancer cachexia progression in the female mouse.

    Science.gov (United States)

    Hetzler, Kimbell L; Hardee, Justin P; LaVoie, Holly A; Murphy, E Angela; Carson, James A

    2017-05-01

    Cachexia is a debilitating condition that occurs with chronic disease, including cancer; our research has shown that some regulation of cancer cachexia progression is affected by sex differences. The Apc Min/+ mouse is genetically predisposed to develop intestinal tumors; IL-6 signaling and hypogonadism are associated with cachexia severity in the male. This relationship in the female warrants further investigation, as we have shown that the ability of IL-6 to induce cachexia differs between the sexes. Since ovarian reproductive function relies on a complex system of endocrine signaling to affect whole body homeostasis, we examined the relationship between ovarian reproductive function and progression of cancer cachexia in the female Apc Min/+ mouse. Our study of ovarian reproductive function in female Apc Min/+ mice showed disease-related cessation of estrous cycling (acyclicity) in 38% of mice. Acyclicity, including morphological and functional losses and enhanced muscle inflammatory gene expression, was associated with severe cachexia. Interestingly, ovariectomy rescued body weight and muscle mass and function but increased muscle sensitivity to systemic IL-6 overexpression. In conclusion, our results provide evidence for a relationship between ovarian reproductive function and cachexia progression in female Apc Min/+ mice. Copyright © 2017 the American Physiological Society.

  14. Whole abdominal irradiation following chemotherapy in advanced ovarian carcinoma

    International Nuclear Information System (INIS)

    Kuten, A.; Stein, M.; Steiner, M.; Rubinov, R.; Epelbaum, R.; Cohen, Y.

    1988-01-01

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

  15. Progress in understanding human ovarian folliculogenesis and its implications in assisted reproduction.

    Science.gov (United States)

    Yang, Dong Zi; Yang, Wan; Li, Yu; He, Zuanyu

    2013-02-01

    To highlight recent progress in understanding the pattern of follicular wave emergence of human menstrual cycle, providing a brief overview of the new options for human ovarian stimulation and oocyte retrieval by making full use of follicular physiological waves of the patients either with normal or abnormal ovarian reserve. Literature review and editorial commentary. There has been increasing evidence to suggest that multiple (two or three) antral follicular waves are recruited during human menstrual cycle. The treatment regimens designed based on the theory of follicular waves, to promote increased success with assisted reproduction technology (ART) and fertility preservation have been reported. These new options for human ovarian stimulation and oocyte retrieval by making full use of follicular waves of the patients either with normal or abnormal ovarian reserve lead to new thinking about the standard protocols in ART and challenge the traditional theory that a single wave of antral follicles grows only during the follicular phase of the menstrual cycle. The understanding of human ovarian folliculogenesis may have profound implications in ART and fertility preservation. Further studies are needed to evaluate the optimal regimens in ART based on the theory of follicular waves and to identify non-invasive markers for predicting the outcome and the potential utilities of follicles obtained from anovulatory follicular waves in ART.

  16. Changes in gene expression and cellular architecture in an ovarian cancer progression model.

    Directory of Open Access Journals (Sweden)

    Amy L Creekmore

    Full Text Available BACKGROUND: Ovarian cancer is the fifth leading cause of cancer deaths among women. Early stage disease often remains undetected due the lack of symptoms and reliable biomarkers. The identification of early genetic changes could provide insights into novel signaling pathways that may be exploited for early detection and treatment. METHODOLOGY/PRINCIPAL FINDINGS: Mouse ovarian surface epithelial (MOSE cells were used to identify stage-dependent changes in gene expression levels and signal transduction pathways by mouse whole genome microarray analyses and gene ontology. These cells have undergone spontaneous transformation in cell culture and transitioned from non-tumorigenic to intermediate and aggressive, malignant phenotypes. Significantly changed genes were overrepresented in a number of pathways, most notably the cytoskeleton functional category. Concurrent with gene expression changes, the cytoskeletal architecture became progressively disorganized, resulting in aberrant expression or subcellular distribution of key cytoskeletal regulatory proteins (focal adhesion kinase, α-actinin, and vinculin. The cytoskeletal disorganization was accompanied by altered patterns of serine and tyrosine phosphorylation as well as changed expression and subcellular localization of integral signaling intermediates APC and PKCβII. CONCLUSIONS/SIGNIFICANCE: Our studies have identified genes that are aberrantly expressed during MOSE cell neoplastic progression. We show that early stage dysregulation of actin microfilaments is followed by progressive disorganization of microtubules and intermediate filaments at later stages. These stage-specific, step-wise changes provide further insights into the time and spatial sequence of events that lead to the fully transformed state since these changes are also observed in aggressive human ovarian cancer cell lines independent of their histological type. Moreover, our studies support a link between aberrant cytoskeleton

  17. Advanced epithelial ovarian cancer: toxicity of whole abdominal irradiation after operation, combination chemotherapy, and reoperation

    International Nuclear Information System (INIS)

    Schray, M.F.; Martinez, A.; Howes, A.E.; Ballon, S.C.; Podratz, K.C.; Sikic, B.I.; Malkasian, G.D.

    1986-01-01

    Thirty-five patients with advanced ovarian cancer have received, as salvage therapy, irradiation consisting of 30 Gy to the entire abdominal contents with partial liver/kidney shielding and boosts to 42 and 51 Gy for the paraaortic/diaphragmatic and pelvic regions, respectively. These patients had received 6 to 25 cycles (median, 11 cycles) of prior combination chemotherapy (included cisplatin in 30), with second-look laparotomy performed in 33; 24 (68%) had three or more laparotomies. Acute gastrointestinal toxicity was generally mild. Significant hematologic toxicity (leukocytes less than 2000/mm3; or platelets less than 100,000/mm3) was seen in 19 (54%); platelet suppression occurred in 18 of these 19. Nine patients failed to complete the prescribed course of therapy; in seven, this was secondary to hematologic toxicity. Amount of prior chemotherapy and advanced age correlated with degree of hematologic toxicity. Five patients without evidence of disease (laparotomy confirmed) have developed treatment-related bowel obstruction. No other chronic toxicity of clinical significance has been observed. Seven patients have developed bowel obstruction associated with progressive neoplasm. Irradiation was well tolerated symptomatically, but hematologic toxicity associated with prior chemotherapy prevented its completion in 20% of patients. Clinical manifestations of radiation bowel toxicity have been moderate to date and should be interpreted in the context of the aggressive combined modality program

  18. Podoplanin as Key Player of Tumor Progression and Lymph Vessel Proliferation in Ovarian Cancer.

    Science.gov (United States)

    Cobec, Ionut Marcel; Sas, Ioan; Pirtea, Laurențiu; Cimpean, Anca Maria; Moatar, Aurica Elisabeta; Ceaușu, Raluca Amalia; Raica, Marius

    2016-10-01

    Podoplanin plays a key role in tumor progression and metastasis. We evaluated lymphatics proliferation rate and podoplanin expression in tumor cells of ovarian carcinoma. Seventy-five paraffin-embedded specimens of ovarian cancer were immunohistochemically assessed in order to quantify peritumoral (LMVDP) and intratumoral (LMVDT) lymphatic microvessel density of proliferating lymphatics and for podoplanin variability in tumor cells. LMVDT correlated with proliferating tumor vessels located in the peritumoral area (p=0.024) and with the number of mature vessels located in the intratumoral area (p<0.0001), while LMVDP correlated with peritumoral mature vessels (p<0.000l). Proliferating tumor cells at the invasive front were highly positive for podoplanin. To the best of our knowledge, this study represents the first assessment of lymphatic endothelial cell proliferation correlated with podoplanin expression in tumor cells from ovarian cancer. Our data support podoplanin as a potential target that may help reduce ovarian cancer dissemination and lymphatic metastasis. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  19. ESTIMATION OF SURVIVAL IN PATIENTS WITH ADVANCED OVARIAN CANCER – ABSTRACT OF THE RESEARCH PROJECT

    Directory of Open Access Journals (Sweden)

    Špela Smrkolj

    2018-02-01

    Full Text Available Background: Morbidity and mortality caused by cancer persist to be an important health problem world- wide and in the European Union member states as well. In Slovenia, most ovarian cancer cases are detected in advanced stages, hence a rather high mortality rate. Aims: The purpose of this research project is to analyze the primary cytoreduction in the patients with advanced ovarian cancer. The main objective of the project is to assess the use of lap- aroscopy in the prediction of optimal cytoreduction in these patients. Applicative research project ‘Estimation of survial in patients with advanced ovarian can- cer based on primary laparoscopical assessment of optimal cytoreduction’ (L3-2371 was approved and has been financed by the Slovene Research Agency and co-financed by the Ministry of Health of RS; Duration: May 1, 2009–April 30, 2012. Methods: The research project will consist of retrospective and prospective study. In all the patients with advanced ovarian cancer managed at the Department of Obstetrics and Gynecol- ogy, University Medical Centre Ljubljana in the years 2003–2008, and in whom optimal primary cytoreduction was made using either laparoscopy or laparotomy, certain clinical and pathomorphological factors will be compared, and the effects of all analyzed factors on the outcome of treatment assessed. In the prospective study, we will aim at assessing the use of laparoscopy in the prediction of optimal cytoreduction in all newly detected cases using a laparoscopy-based score (Fagotti’s scoring system. Conclusions: The standard management of advanced ovarian cancer patients consists of primary surgical optimal and/or suboptimal cytoreduction followed by aggressive cytotoxic chemotherapy. In line with our experience and with that published most recently, laparoscopy seems to be a promising method with which we will attempt to most accurately assess the optimal cytoreduction in surgical treatment of ovarian cancer patients.

  20. Recent advances in the field of ovarian tissue cryopreservation and opportunities for research.

    Science.gov (United States)

    Ladanyi, Camille; Mor, Amir; Christianson, Mindy S; Dhillon, Namisha; Segars, James H

    2017-06-01

    The purpose of this study was to summarize the latest advances and successes in the field of ovarian tissue cryopreservation while identifying gaps in current knowledge that suggest opportunities for future research. A systematic review was performed according to PRISMA guidelines for all relevant full-text articles in PubMed published in English that reviewed or studied historical or current advancements in ovarian tissue cryopreservation and auto-transplantation techniques. Ovarian tissue auto-transplantation in post-pubertal women is capable of restoring fertility with over 80 live births currently reported with a corresponding pregnancy rate of 23 to 37%. The recently reported successes of live births from transplants, both in orthotopic and heterotopic locations, as well as the emerging methods of in vitro maturation (IVM), in vitro culture of primordial follicles, and possibility of in vitro activation (IVA) suggest new fertility options for many women and girls. Vitrification, as an ovarian tissue cryopreservation technique, has also demonstrated successful live births and may be a more cost-effective method to freezing with less tissue injury. Further, transplantation via the artificial ovary with an extracellular tissue matrix (ECTM) scaffolding as well as the effects of sphingosine-1-phosphate (SIP) and fibrin modified with heparin-binding peptide (HBP), heparin, and a vascular endothelial growth factor (VEGF) have demonstrated important advancements in fertility preservation. As a fertility preservation method, ovarian tissue cryopreservation and auto-transplantation are currently considered experimental, but future research may pave the way for these modalities to become a standard of care for women facing the prospect of sterility from ovarian damage.

  1. Sequential cisplatin/cyclophosphamide chemotherapy and abdominopelvic radiotherapy in the management of advanced ovarian cancer.

    Science.gov (United States)

    Green, J A; Warenius, H M; Errington, R D; Myint, S; Spearing, G; Slater, A J

    1988-11-01

    Forty-six previously untreated patients with advanced ovarian cancer were treated with combination chemotherapy comprising cisplatin 80 mg m-2 i.v. and cyclophosphamide 1 gm-2 i.v. every 28 days for 5 cycles. Eighty-five percent of patients received more than 75% of the calculated doses, and of 43 evaluable patients, a complete response was achieved in 31 (72%), a partial response in 4 (9.3%) and 8 patients had static or progressive disease. The actuarial survival of the whole group is 60% at a median follow-up of 2 years. Twenty-four patients in complete clinical or pathological remission were then treated with whole abdominal radiotherapy 2,500 cGy followed by a pelvic boost of 2,000 cGy. The pelvic boost was omitted in 3 patients, and the overall radiotherapy treatment time extended in a further 4 patients on account of myelosuppression. The actuarial survival of the 24 patients receiving both treatments at a median of 30 months follow-up is 75%. In the 10 patients with negative second-look procedures completing both treatments there have been no tumour related deaths at a median follow-up of 33 months.

  2. Electroacupuncture decreases the progression of ovarian hyperstimulation syndrome in a rat model.

    Science.gov (United States)

    Chen, Li; Sun, Hai-Xiang; Xia, You-Bing; Sui, Liu-Cai; Zhou, Ji; Huang, Xuan; Zhou, Jing-Wei; Shao, Yi-Dan; Shen, Tao; Sun, Qin; Liang, Yuan-Jiao; Yao, Bing

    2016-05-01

    This study aimed to elucidate the effect of electroacupuncture treatment on preventing early ovarian hyperstimulation syndrome (OHSS) and the potential mechanisms involved using an induced rat model. The ovarian response was examined by measuring ovary weight, vascular permeability, levels of inflammation (interleukin-6), tumour necrosis factor alpha, chemokine ligand 2 (also known as monocyte chemoactic protein 1), vascular endothelial growth factor and hormone concentrations (oestradiol, progesterone, testosterone and prolactin). Sprague-Dawley female rats underwent ovarian stimulation to induce OHSS. Hyperstimulated rats received consecutive electroacupuncture treatment from 3 days before the beginning of pregnant mare serum gonadotrophin treatment or the time point of pregnant mare serum gonadotrophin treatment respectively, and last until 3 days after HCG administration. Electroacupuncture treatment reduced ovary weight and vascular permeability in hyperstimulated rats. Electroacupuncture treatment also reduced the levels of serum steroid hormones (progesterone and testosterone), inflammatory cytokines (interleukin-6, tumour necrosis factor alpha and monocyte chemotactic protein 1 and vascular endothelial growth factor in hyperstimulated rats. The results indicate that electroacupuncture can modulate endocrine hormone secretion and affect the secretion of inflammatory cytokines and vascular endothelial growth factor, and thus prevent the progress of OHSS. Electroacupuncture may provide a simple and effective method for the prevention and treatment of OHSS. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

    International Nuclear Information System (INIS)

    Rochet, Nathalie; Sterzing, Florian; Jensen, Alexandra D.; Dinkel, Julien; Herfarth, Klaus K.; Schubert, Kai; Eichbaum, Michael H.; Schneeweiss, Andreas; Sohn, Christof; Debus, Juergen; Harms, Wolfgang

    2010-01-01

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

  4. Intensity-modulated whole abdominal radiotherapy after surgery and carboplatin/taxane chemotherapy for advanced ovarian cancer: phase I study.

    Science.gov (United States)

    Rochet, Nathalie; Sterzing, Florian; Jensen, Alexandra D; Dinkel, Julien; Herfarth, Klaus K; Schubert, Kai; Eichbaum, Michael H; Schneeweiss, Andreas; Sohn, Christof; Debus, Juergen; Harms, Wolfgang

    2010-04-01

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

  5. New advances in ovarian autotransplantation to restore fertility in cancer patients.

    Science.gov (United States)

    Salama, Mahmoud; Woodruff, Teresa K

    2015-12-01

    Human ovary autotransplantation is a promising option for fertility preservation of young women and girls undergoing gonadotoxic treatments for cancer or some autoimmune diseases. Although experimental, it resulted in at least 42 healthy babies worldwide. According to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic literature review was performed for all relevant full-text articles published in English from 1 January 2000 to 01 October 2015 in PubMed to explore the latest clinical and research advances of human ovary autotransplantation. Human ovary autotransplantation involves ovarian tissue extraction, freezing/thawing, and transplantation back into the same patient. Three major forms of human ovary autotransplantation exist including (a) transplantation of cortical ovarian tissue, (b) transplantation of whole ovary, and (c) transplantation of ovarian follicles (artificial ovary). According to the recent guidelines, human ovary autotransplantation is still considered experimental; however, it has unique advantages in comparison to other options of female fertility preservation. Human ovary autotransplantation (i) does not need prior ovarian stimulation, (ii) allows immediate initiation of cancer therapy, (iii) can restore both endocrine and reproductive ovarian functions, and (iv) may be the only fertility preservation option suitable for prepubertal girls or for young women with estrogen-sensitive malignancies. As any other fertility preservation option, human ovary autotransplantation has both advantages and disadvantages and may not be feasible for all cases. The major challenges facing this option are how to avoid the risk of reintroducing malignant cells and how to prolong the lifespan of ovarian transplant as well as how to improve artificial ovary results.

  6. Posterior pelvic exenteration and retrograde total hysterectomy in patients with locally advanced ovarian cancer: Clinical and functional outcome

    Directory of Open Access Journals (Sweden)

    Roberto Berretta

    2016-06-01

    Conclusion: Our study confirmed that pelvic posterior exenteration associated with retrograde radical hysterectomy represents the safest radical surgical approach to advanced ovarian cancer, which permits preservation of the pelvic autonomic nerve plexus and, therefore, bladder and colorectal functions.

  7. Clinical factors of response in patients with advanced ovarian cancer participating in early phase clinical trials.

    Science.gov (United States)

    George, Angela; Kristeleit, Rebecca; Rafii, Saeed; Michie, Caroline O; Bowen, Rebecca; Michalarea, Vasiliki; van Hagen, Tom; Wong, Mabel; Rallis, Grigorios; Molife, L Rhoda; Lopez, Juanita; Banerji, Udai; Banerjee, Susana N; Gore, Martin E; de Bono, Johann S; Kaye, Stan B; Yap, Timothy A

    2017-05-01

    Drug resistance to conventional anticancer therapies is almost inevitable in patients with advanced ovarian cancer (AOC), limiting their available treatment options. Novel phase I trial therapies within a dedicated drug development unit may represent a viable alternative; however, there is currently little evidence for patient outcomes in such patients. To address this, we undertook a retrospective review of patients with AOC allocated to phase I trials in the Drug Development Unit at Royal Marsden Hospital (RMH) between June 1998 and October 2010. A total of 200 AOC patients with progressive disease were allocated to ≥1 trial each, with a total of 281 allocations. Of these, 135 (68%) patients commenced ≥1 trial (mean 1.4 [1-8]), totaling 216 allocated trials; 65 (32%) patients did not start due to deterioration resulting from rapidly progressive disease (63 patients) or patient choice (2 patients). Response Evaluation Criteria in Solid Tumours (RECIST) complete/partial responses (CR/PR) were observed in 43 (20%) of those starting trials, including those on poly(ADP-ribose) polymerase (PARP) inhibitors (18/79 [23%]), antiangiogenics (9/65 [14%]) and chemotherapy combinations (14/43 [33%]). Factors associated with CR/PR included: fewer prior treatments, platinum-sensitive disease, CR/PR with prior therapy, (the United States-based) Eastern Cooperative Oncology Group (ECOG) performance status score, fewer metastatic sites, higher albumin and haemoglobin levels, lower white cell counts and baseline CA125 levels, germline BRCA1/2 mutations and better RMH Prognostic Score. Mean survival was 32° months for patients who achieved CR/PR. Treatments were generally well tolerated. Most patients with AOC (134/200 [67%]) received ≥1 subsequent line of therapy after phase I trials. Our data suggest that phase I trial referrals should be considered earlier in the AOC treatment pathway and before the onset of rapid disease progression particularly with the emergence of

  8. Prognostic significance of normal-sized ovary in advanced serous epithelial ovarian cancer.

    Science.gov (United States)

    Paik, E Sun; Kim, Ji Hye; Kim, Tae Joong; Lee, Jeong Won; Kim, Byoung Gie; Bae, Duk Soo; Choi, Chel Hun

    2018-01-01

    We compared survival outcomes of advanced serous type epithelial ovarian cancer (EOC) patients with normal-sized ovaries and enlarged-ovarian tumors by propensity score matching analysis. The medical records of EOC patients treated at Samsung Medical Center between 2002 and 2015 were reviewed retrospectively. We investigated EOC patients with high grade serous type histology and International Federation of Gynecology and Obstetrics (FIGO) stage IIIB, IIIC, or IV who underwent primary debulking surgery (PDS) and adjuvant chemotherapy to identify patients with normal-sized ovaries. Propensity score matching was performed to compare patients with normal-sized ovaries to patients with enlarged-ovarian tumors (ratio, 1:3) according to age, FIGO stage, initial cancer antigen (CA)-125 level, and residual disease status after PDS. Of the 419 EOC patients, 48 patients had normal-sized ovary. Patients with enlarged-ovarian tumor were younger (54.0±10.3 vs. 58.4±9.2 years, p=0.005) than those with normal-sized ovary, and there was a statistically significant difference in residual disease status between the 2 groups. In total cohort with a median follow-up period of 43 months (range, 3-164 months), inferior overall survival (OS) was shown in the normal-sized ovary group (median OS, 71.2 vs. 41.4 months; p=0.003). After propensity score matching, the group with normal-sized ovary showed inferior OS compared to the group with enlarged-ovarian tumor (median OS, 72.1 vs. 41.4 months; p=0.031). In multivariate analysis for OS, normal-sized ovary remained a significant factor. Normal-sized ovary was associated with poor OS compared with the common presentation of enlarged ovaries in EOC, independent of CA-125 level or residual disease. Copyright © 2018. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology

  9. Dynamics of the Intratumoral Immune Response during Progression of High-Grade Serous Ovarian Cancer

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    Mandy Stanske

    2018-03-01

    Full Text Available PURPOSE: Tumor-infiltrating lymphocytes (TILs have an established impact on the prognosis of high-grade serous ovarian carcinoma (HGSOC, however, their role in recurrent ovarian cancer is largely unknown. We therefore systematically investigated TIL densities and MHC class I and II (MHC1, 2 expression in the progression of HGSOC. EXPERIMENTAL DESIGN: CD3+, CD4+, CD8+ TILs and MHC1, 2 expression were evaluated by immunohistochemistry on tissue microarrays in 113 paired primary and recurrent HGSOC. TILs were quantified by image analysis. All patients had been included to the EU-funded OCTIPS FP7 project. RESULTS: CD3+, CD4+, CD8+ TILs and MHC1 and MHC2 expression showed significant correlations between primary and recurrent tumor levels (Spearman rho 0.427, 0.533, 0.361, 0.456, 0.526 respectively; P<.0001 each. Paired testing revealed higher CD4+ densities and MHC1 expression in recurrent tumors (Wilcoxon P=.034 and P=.018. There was also a shift towards higher CD3+ TILs levels in recurrent carcinomas when analyzing platinum-sensitive tumors only (Wilcoxon P=.026 and in pairs with recurrent tumor tissue from first relapse only (Wilcoxon P=.031. High MHC2 expression was the only parameter to be significantly linked to prolonged progression-free survival after first relapse (PFS2, log-rank P=.012. CONCLUSIONS: This is the first study that analyzed the development of TILs density and MHC expression in paired primary and recurrent HGSOC. The level of the antitumoral immune response in recurrent tumors was clearly dependent on the one in the primary tumor. Our data contribute to the understanding of temporal heterogeneity of HGSOC immune microenvironment and have implications for selection of samples for biomarker testing in the setting of immune-targeting therapeutics.

  10. Advanced ovarian cancer: phase III randomized study of sequential cisplatin-topotecan and carboplatin-paclitaxel vs carboplatin-paclitaxel.

    Science.gov (United States)

    Hoskins, P; Vergote, I; Cervantes, A; Tu, D; Stuart, G; Zola, P; Poveda, A; Provencher, D; Katsaros, D; Ojeda, B; Ghatage, P; Grimshaw, R; Casado, A; Elit, L; Mendiola, C; Sugimoto, A; D'Hondt, V; Oza, A; Germa, J R; Roy, M; Brotto, L; Chen, D; Eisenhauer, E A

    2010-10-20

    Topotecan has single-agent activity in recurrent ovarian cancer. It was evaluated in a novel combination compared with standard frontline therapy. Women aged 75 years or younger with newly diagnosed stage IIB or greater ovarian cancer, Eastern Cooperative Oncology Group Performance Status of 1 or less, were stratified by type of primary surgery and residual disease, treatment center, and age; then randomly assigned to one of the two 21-day intravenous regimens. Patients in arm 1 (n = 409) were administered four cycles of cisplatin 50 mg/m(2) on day 1 and topotecan 0.75 mg/m(2) on days 1-5, then four cycles of paclitaxel 175 mg/m(2) over 3 hours on day 1 followed by carboplatin (area under the curve = 5) on day 1. Patients in arm 2 (n = 410) were given paclitaxel plus carboplatin as in arm 1 for eight cycles. We compared progression-free survival (PFS), overall survival, and cancer antigen-125 normalization rates in the two treatment arms. A stratified log-rank test was used to assess the primary endpoint, PFS. All statistical tests were two-sided. A total of 819 patients were randomly assigned. At baseline, the median age of the patients was 57 years (range = 28-78); 81% had received debulking surgery, and of these, 55% had less than 1 cm residual disease; 66% of patients were stage III and 388 (47.4%) patients had measurable disease. After a median follow-up of 43 months, 650 patients had disease progression or died without documented progression and 406 had died. Patients in arm 1 had more hematological toxicity and hospitalizations than patients in arm 2; PFS was 14.6 months in arm 1 vs 16.2 months in arm 2 (hazard ratio = 1.10, 95% confidence interval = 0.94 to 1.28, P = .25). Among patients with elevated baseline cancer antigen-125, fewer in arm 1 than in arm 2 had levels return to normal by 3 months after random assignment (51.6% vs 63.3%, P = .007) Topotecan and cisplatin, followed by carboplatin and paclitaxel, were more toxic than carboplatin and

  11. Chemotherapy in advanced ovarian cancer: four systematic meta-analyses of individual patient data from 37 randomized trials. Advanced Ovarian Cancer Trialists' Group.

    Science.gov (United States)

    Aabo, K.; Adams, M.; Adnitt, P.; Alberts, D. S.; Athanazziou, A.; Barley, V.; Bell, D. R.; Bianchi, U.; Bolis, G.; Brady, M. F.; Brodovsky, H. S.; Bruckner, H.; Buyse, M.; Canetta, R.; Chylak, V.; Cohen, C. J.; Colombo, N.; Conte, P. F.; Crowther, D.; Edmonson, J. H.; Gennatas, C.; Gilbey, E.; Gore, M.; Guthrie, D.; Yeap, B. Y.

    1998-01-01

    The purpose of this systematic study was to provide an up to date and reliable quantitative summary of the relative benefits of various types of chemotherapy (non-platinum vs platinum, single-agent vs combination and carboplatin vs cisplatin) in the treatment of advanced ovarian cancer. Also, to investigate whether well-defined patient subgroups benefit more or less from cisplatin- or carboplatin-based therapy. Meta-analyses were based on updated individual patient data from all available randomized controlled trials (published and unpublished), including 37 trials, 5667 patients and 4664 deaths. The results suggest that platinum-based chemotherapy is better than non-platinum therapy, show a trend in favour of platinum combinations over single-agent platinum, and suggest that cisplatin and carboplatin are equally effective. There is no good evidence that cisplatin is more or less effective than carboplatin in any particular subgroup of patients. Images Figure 1 Figure 2 Figure 3 PMID:9836481

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

    Science.gov (United States)

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

    2016-09-01

    The surgical management of advanced ovarian cancer involves complex surgery. Implementation of a quality management program has a major impact on survival. The goal of this work was to develop a list of quality indicators (QIs) for advanced ovarian cancer surgery that can be used to audit and improve the clinical practice. This task has been carried out under the auspices of the European Society of Gynaecologic Oncology (ESGO). Quality indicators were based on scientific evidence and/or expert consensus. A 4-step evaluation process included a systematic literature search for the identification of potential QIs and the documentation of scientific evidence, physical meetings of an ad hoc multidisciplinarity International Development Group, an internal validation of the targets and scoring system, and an external review process involving physicians and patients. Ten structural, process, or outcome indicators were selected. Quality indicators 1 to 3 are related to achievement of complete cytoreduction, caseload in the center, training, and experience of the surgeon. Quality indicators 4 to 6 are related to the overall management, including active participation to clinical research, decision-making process within a structured multidisciplinary team, and preoperative workup. Quality indicator 7 addresses the high value of adequate perioperative management. Quality indicators 8 to 10 highlight the need of recording pertinent information relevant to improvement of quality. An ESGO-approved template for the operative report has been designed. Quality indicators were described using a structured format specifying what the indicator is measuring, measurability specifications, and targets. Each QI was associated with a score, and an assessment form was built. The ESGO quality criteria can be used for self-assessment, for institutional or governmental quality assurance programs, and for the certification of centers. Quality indicators and corresponding targets give

  13. Role of Chemokine Network in the Development and Progression of Ovarian Cancer: A Potential Novel Pharmacological Target

    Directory of Open Access Journals (Sweden)

    Federica Barbieri

    2010-01-01

    Full Text Available Ovarian cancer is the most common type of gynecologic malignancy. Despite advances in surgery and chemotherapy, the survival rate is still low since most ovarian cancers relapse and become drug-resistant. Chemokines are small chemoattractant peptides mainly involved in the immune responses. More recently, chemokines were also demonstrated to regulate extra-immunological functions. It was shown that the chemokine network plays crucial functions in the tumorigenesis in several tissues. In particular the imbalanced or aberrant expression of CXCL12 and its receptor CXCR4 strongly affects cancer cell proliferation, recruitment of immunosuppressive cells, neovascularization, and metastasization. In the last years, several molecules able to target CXCR4 or CXCL12 have been developed to interfere with tumor growth, including pharmacological inhibitors, antagonists, and specific antibodies. This chemokine ligand/receptor pair was also proposed to represent an innovative therapeutic target for the treatment of ovarian cancer. Thus, a thorough understanding of ovarian cancer biology, and how chemokines may control these different biological activities might lead to the development of more effective therapies. This paper will focus on the current biology of CXCL12/CXCR4 axis in the context of understanding their potential role in ovarian cancer development.

  14. Deregulation of microcephalin and ASPM expression are correlated with epithelial ovarian cancer progression.

    Directory of Open Access Journals (Sweden)

    Rawiah Alsiary

    Full Text Available Mutations in the MCPH1 (Microcephalin and ASPM (abnormal spindle-like microcephaly associated genes cause primary microcephaly. Both are centrosomal associated proteins involved in mitosis. Microcephalin plays an important role in DNA damage response and ASPM is required for correct division of proliferative neuro-epithelial cells of the developing brain. Reduced MCPH1 mRNA expression and ASPM mRNA over-expression have been implicated in the development of human carcinomas. Epithelial ovarian cancer (EOC is characterised by highly aneuploid tumours. Previously we have reported low Microcephalin and high ASPM protein levels and associations with clinico-pathological parameters in malignant cells from ascitic fluids. To confirm these previous findings on a larger scale Microcephalin and ASPM expression levels and localisations were evaluated by immunohistochemistry in two cohorts; a training set of 25 samples and a validation set of 322 EOC tissue samples. Results were correlated to the associated histopathological data. In normal ovarian tissues the Microcephalin nuclear staining pattern was consistently strong. In the cancer tissues, we identified low nuclear Microcephalin expression in high grade and advanced stage tumours (p<0.0001 and p = 0.0438 respectively. ASPM had moderate to high nuclear and low to moderate cytoplasmic expression in normal tissue. Cytoplasmic ASPM expression decreased with tumour grade and stage in the serous subtype of EOC (p = 0.023 and p = 0.011 respectively. Cytoplasmic ASPM increased with tumour stage in the endometrioid subtype (p = 0.023. Increasing tumour invasiveness (T3 and lymph node involvement (N1 also correlated with a decrease in cytoplasmic ASPM in EOC (p = 0.02 and p = 0.04 respectively. We have validated previous findings of deregulated expression of Microcephalin and ASPM in EOC by confirming associations for low nuclear Microcephalin levels and high cytoplasmic ASPM levels in a larger scale tumour

  15. Are Early Relapses in Advanced-Stage Ovarian Cancer Doomed to a Poor Prognosis?

    Directory of Open Access Journals (Sweden)

    Fabien Vidal

    Full Text Available Early recurrence (ER after completion of therapeutic regimen in advanced-stage ovarian cancer is a challenging clinical situation. Patients are perceived as invariably having a poor prognosis. We investigated the possibility of defining different prognostic subgroups and the parameters implicated in prognosis of ER patients.We analyzed a multi-centric database of 527 FIGO stage IIIC and IV ovarian cancer patients. We defined patients relapsing within 12 months as ER and investigated using Cox logistic regression the prognostic factors in ER group. We subsequently divided ER patients into good and poor prognosis groups according to a lower or higher overall survival (OS at 12 months after relapse and determined parameters associated to poor prognosis.The median follow up was 49 months. One hundred and thirty eight patients recurred within 12 months. OS and Disease Free Survival (DFS were 24.6 and 8.6 months, respectively, in this group of patients. Among the ER patients, 73 had a poor prognosis with an OS after relapse below 12 months (mean OS = 5.2 months and 65 survived after one year (mean OS = 26.9 months. Residual disease (RD after debulking surgery and mucinous histological subtype negatively impacted prognosis (HR = 1.758, p = 0.017 and HR = 8.641, p = 0.001 respectively. The relative risk of death within 12 months following relapse in ER patients was 1.61 according to RD status. However, RD did not affect DFS (HR = 0.889, p = 0.5.ER in advanced-stage ovarian cancer does not inevitably portend a short-term poor prognosis. RD status after initial cytoreduction strongly modulates OS, that gives additional support to the concept of maximum surgical effort even in patients who will experience early recurrence. The heterogeneity in outcomes within the ER group suggests a role for tumor biology in addition to classical clinical parameters.

  16. The importance of second-look surgery following radio-chemotherapy for advanced ovarian cancer

    International Nuclear Information System (INIS)

    Janisch, H.; Gerstner, G.

    1980-01-01

    Fifteen patients with advanced, initially inoperable ovarian cancer (stages III and IV) were subjected to second-look surgery between May 1976 and August 1979 following combined radio-chemotherapy. Each case had shown a distinct reduction in tumour size and a demarcation of the foreign issue, which is considered to be prerequisite for second-look surgery. The diagnostic goal of the operation was to verify the success of the preceding radio-chemotherapeutic treatment by means of exact determination of the extent of the residual tumour. The subsequent therapeutic regimen can, if necessary, be modified accordingly. The therapeutic goal is complete surgical removal of the tumour, if at all possible, since the success of subsequent chemotherapy is dependent on the achievement of this aim. The mean interval between initial and second-look surgery was three and a half months. Tumour tissue of varying extent was found in 14 out of 15 cases. In 12 cases total extirpation of the internal genitals was successfully carried out, tumour resection was performed twice, and only of third-look surgery, when after two years of radio-chemotherapy and secondary removal of the internal genitals abdominal tumour diagnosis this patient is now undergoing further chemotherapeutic treatment. We believe that this very case illustrates the importance of second-look surgery and of consistent continuation with radio-chemotherapy in cases of advanced inoperable ovarian cancer. (author)

  17. Two microRNA signatures for malignancy and immune infiltration predict overall survival in advanced epithelial ovarian cancer.

    Science.gov (United States)

    Korsunsky, Ilya; Parameswaran, Janaki; Shapira, Iuliana; Lovecchio, John; Menzin, Andrew; Whyte, Jill; Dos Santos, Lisa; Liang, Sharon; Bhuiya, Tawfiqul; Keogh, Mary; Khalili, Houman; Pond, Cassandra; Liew, Anthony; Shih, Andrew; Gregersen, Peter K; Lee, Annette T

    2017-10-01

    MicroRNAs have been established as key regulators of tumor gene expression and as prime biomarker candidates for clinical phenotypes in epithelial ovarian cancer (EOC). We analyzed the coexpression and regulatory structure of microRNAs and their co-localized gene targets in primary tumor tissue of 20 patients with advanced EOC in order to construct a regulatory signature for clinical prognosis. We performed an integrative analysis to identify two prognostic microRNA/mRNA coexpression modules, each enriched for consistent biological functions. One module, enriched for malignancy-related functions, was found to be upregulated in malignant versus benign samples. The second module, enriched for immune-related functions, was strongly correlated with imputed intratumoral immune infiltrates of T cells, natural killer cells, cytotoxic lymphocytes, and macrophages. We validated the prognostic relevance of the immunological module microRNAs in the publicly available The Cancer Genome Atlas data set. These findings provide novel functional roles for microRNAs in the progression of advanced EOC and possible prognostic signatures for survival. © American Federation for Medical Research (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  18. Nuclear expression of Snail1 in borderline and malignant epithelial ovarian tumours is associated with tumour progression

    International Nuclear Information System (INIS)

    Tuhkanen, Hanna; Soini, Ylermi; Kosma, Veli-Matti; Anttila, Maarit; Sironen, Reijo; Hämäläinen, Kirsi; Kukkonen, Laura; Virtanen, Ismo; Mannermaa, Arto

    2009-01-01

    Transcription factor Snail1 has a central role in induction of epithelial-mesenchymal transition (EMT). The aim of the present study was to elucidate the expression of Snail1 protein during epithelial ovarian tumourigenesis and to study the association of Snail1 expression with clinicopathological factors and prognosis. Epithelial and stromal fibroblast-like fusiform cells of 14 normal ovarian samples, 21 benign, 24 borderline and 74 malignant epithelial ovarian tumours were studied for Snail1 protein using immunohistochemistry. Nuclei of surface peritoneal cells of normal ovaries (n = 14) were regarded as negative for Snail1. Nuclear expression of Snail1 protein in epithelial ovarian tumours was increased during tumour progression from precursor lesions into carcinomas both in epithelial (p = 0.006) and stromal cells (p = 0.007). Nuclei of benign tumours (n = 21) were negative for Snail1. In borderline tumours (n = 24) occasional positive epithelial cells were found in 2 (8%) samples and in 3 (13%) samples stromal cells were focally positive for Snail1. In carcinomas (n = 74) focal Snail1 staining in epithelial cells was present in 17 (23%) tumours, and in stromal cells in 18 (24%) tumours. Nuclear expression of Snail1 in epithelial or stromal cells was not associated with clinicopathological factors or prognosis. Nuclear Snail1 expression seems to be related to tumour progression, and expression in borderline tumours indicates a role for Snail1 in early epithelial ovarian tumour development. Snail1 also appears to function more generally in tissue remodelling as positive staining was demonstrated in stromal cells

  19. Advanced Neutron Source (ANS) Project progress report

    International Nuclear Information System (INIS)

    McBee, M.R.; Chance, C.M.

    1990-04-01

    This report discusses the following topics on the advanced neutron source: quality assurance (QA) program; reactor core development; fuel element specification; corrosion loop tests and analyses; thermal-hydraulic loop tests; reactor control concepts; critical and subcritical experiments; material data, structural tests, and analysis; cold source development; beam tube, guide, and instrument development; hot source development; neutron transport and shielding; I ampersand C research and development; facility concepts; design; and safety

  20. Advances in insect physiology. Progress in mosquito research

    Science.gov (United States)

    This book review briefly summarizes the most interesting topics/chapters from the book: "Advances in Insect Physiology: Progress in mosquito Research". The book is an excellent overview of the recent advances in mosquito biology. This volume encompasses 13 chapters from 32 contributing authors who ...

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

    Directory of Open Access Journals (Sweden)

    Eichbaum Michael H

    2011-01-01

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

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

    International Nuclear Information System (INIS)

    Rochet, Nathalie; Debus, Juergen; Kieser, Meinhard; Sterzing, Florian; Krause, Sonja; Lindel, Katja; Harms, Wolfgang; Eichbaum, Michael H; Schneeweiss, Andreas; Sohn, Christof

    2011-01-01

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

  3. Perovskite Solar Cells: Progress and Advancements

    Directory of Open Access Journals (Sweden)

    Naveen Kumar Elumalai

    2016-10-01

    Full Text Available Organic–inorganic hybrid perovskite solar cells (PSCs have emerged as a new class of optoelectronic semiconductors that revolutionized the photovoltaic research in the recent years. The perovskite solar cells present numerous advantages include unique electronic structure, bandgap tunability, superior charge transport properties, facile processing, and low cost. Perovskite solar cells have demonstrated unprecedented progress in efficiency and its architecture evolved over the period of the last 5–6 years, achieving a high power conversion efficiency of about 22% in 2016, serving as a promising candidate with the potential to replace the existing commercial PV technologies. This review discusses the progress of perovskite solar cells focusing on aspects such as superior electronic properties and unique features of halide perovskite materials compared to that of conventional light absorbing semiconductors. The review also presents a brief overview of device architectures, fabrication methods, and interface engineering of perovskite solar cells. The last part of the review elaborates on the major challenges such as hysteresis and stability issues in perovskite solar cells that serve as a bottleneck for successful commercialization of this promising PV technology.

  4. Recent progress of the advanced test accelerator

    International Nuclear Information System (INIS)

    Prono, D.S.

    1985-01-01

    The Advanced Test Accelerator (ATA) of Lawrence Livermore National Laboratory is a linear induction accelerator whose electron beam parameters are 10 kA, 50 MeV, and 70 ns. This accelerator structure basically is a 2.5 MeV injector followed by 190 identical induction accelerator cores each of which incrementally adds 250 kV to the electron beam as it threads the center of the core. Recent work on beam stability, beam emittance and beam brightness is reported

  5. Single-gene prognostic signatures for advanced stage serous ovarian cancer based on 1257 patient samples.

    Science.gov (United States)

    Zhang, Fan; Yang, Kai; Deng, Kui; Zhang, Yuanyuan; Zhao, Weiwei; Xu, Huan; Rong, Zhiwei; Li, Kang

    2018-04-16

    We sought to identify stable single-gene prognostic signatures based on a large collection of advanced stage serous ovarian cancer (AS-OvCa) gene expression data and explore their functions. The empirical Bayes (EB) method was used to remove the batch effect and integrate 8 ovarian cancer datasets. Univariate Cox regression was used to evaluate the association between gene and overall survival (OS). The Database for Annotation, Visualization and Integrated Discovery (DAVID) tool was used for the functional annotation of genes for Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The batch effect was removed by the EB method, and 1257 patient samples were used for further analysis. We selected 341 single-gene prognostic signatures with FDR matrix organization, focal adhesion and DNA replication which are closely associated with cancer. We used the EB method to remove the batch effect of 8 datasets, integrated these datasets and identified stable prognosis signatures for AS-OvCa.

  6. Ten years of "Optimal Therapy in Advanced Ovarian Cancer. Update" meeting.

    Science.gov (United States)

    Poveda, A

    2008-01-01

    The International Symposium on Advanced Ovarian Cancer: Optimal Therapy was founded by Dr. Andrés Poveda and Prof. Jan B. Vermorken, and each edition has been directed by them. The 6th edition was held on March 2, 2007. This symposium is organized every other year by GEICO (Grupo Español de Investigación de Cáncer de Ovario/Spanish Ovarian Cancer Research Group), under the auspices of the Spanish Society of Medical Oncology (SEOM), the Gynecologic Cancer Intergroup (GCIG), and the European Society of Medical Oncology (ESMO) Educational Committee for its Medical Oncology Recertification Approval (ESMO/MORA) Program. One hundred and fifty people attended the symposium's 1st edition, held in 1996. Since then, the interest in this meeting has increased. Last year, almost three hundred people coming not only from Spain but also from Europe, North and Latin America, Asia, and Australia were present in the symposium. This is a great challenge for us. Some important international cooperative groups from Europe, America, and Australia collaborate with this symposium, such as GOG, NCIC, EORTC, AGO, Scottish Group, ICON, GINECO, NSGO, ANZGOG, and others.

  7. Advanced CANDU reactor pre-licensing progress

    International Nuclear Information System (INIS)

    Popov, N.K.; West, J.; Snell, V.G.; Ion, R.; Archinoff, G.; Xu, C.

    2005-01-01

    The Advanced CANDU Reactor (ACR) is an evolutionary advancement of the current CANDU 6 reactor, aimed at producing electrical power for a capital cost and at a unit-energy cost significantly less than that of the current reactor designs. The Canadian Nuclear Safety Commission (CNSC) staff are currently reviewing the ACR design to determine whether, in their opinion, there are any fundamental barriers that would prevent the licensing of the design in Canada. This CNSC licensability review will not constitute a licence, but is expected to reduce regulatory risk. The CNSC pre-licensing review started in September 2003, and was focused on identifying topics and issues for ACR-700 that will require a more detailed review. CNSC staff reviewed about 120 reports, and issued to AECL 65 packages of questions and comments. Currently CNSC staff is reviewing AECL responses to all packages of comments. AECL has recently refocused the design efforts to the ACR-1000, which is a larger version of the ACR design. During the remainder of the pre-licensing review, the CNSC review will be focused on the ACR-1000. AECL Technologies Inc. (AECLT), a wholly-owned US subsidiary of AECL, is engaged in a pre-application process for the ACR-700 with the US Nuclear Regulatory Commission (USNRC) to identify and resolve major issues prior to entering a formal process to obtain standard design certification. To date, the USNRC has produced a Pre-Application Safety Assessment Report (PASAR), which contains their reviews of key focus topics. During the remainder of the pre-application phase, AECLT will address the issues identified in the PASAR. Pursuant to the bilateral agreement between AECL and the Chinese nuclear regulator, the National Nuclear Safety Administration (NNSA) and its Nuclear Safety Center (NSC), NNSA/NSC are reviewing the ACR in seven focus areas. The review started in September 2004, and will take three years. The main objective of the review is to determine how the ACR complies

  8. Nomogram for 30-day morbidity after primary cytoreductive surgery for advanced stage ovarian cancer.

    Science.gov (United States)

    Nieuwenhuyzen-de Boer, G M; Gerestein, C G; Eijkemans, M J C; Burger, C W; Kooi, G S

    2016-01-01

    Extensive surgical procedures to achieve maximal cytoreduction in patients with advanced stage epithelial ovarian cancer (EOC) are inevitably associated with postoperative morbidity and mortality. This study aimed to identify preoperative predictors of 30-day morbidity after primary cytoreductive surgery for advanced stage EOC and to develop a nomogram for individual risk assessment. Patients in The Netherlands who underwent primary cytoreductive surgery for advanced stage EOC between January 2004 and December 2007. All peri- and postoperative complications within 30 days after surgery were registered and classified. To investigate predictors of 30-day morbidity, a Cox proportional hazard model with backward stepwise elimination was utilized. The identified predictors were entered into a nomogram. The main outcome was to identify parameters that predict operative risk. 293 patients entered the study protocol. Optimal cytoreduction was achieved in 136 (46%) patients. Thirty-day morbidity was seen in 99 (34%) patients. Morbidity could be predicted by age (p = 0.033; OR 1.024), preoperative hemoglobin (p = 0.194; OR 0.843), and WHO performance status (p = 0.015; OR 1.821) with a optimism-corrected c-statistic of 0.62. Determinants co-morbidity status, serum CA125 level, platelet count, and presence of ascites were comparable in both groups. Thirty-day morbidity after primary cytoreductive surgery for advanced stage EOC could be predicted by age, hemoglobin, and WHO performance status. The generated nomogram could be valuable for predicting operative risk in the individual patient.

  9. Combined carboplatin plus ifosfamide and cisplatin in patients with advanced ovarian carcinoma. A phase I-II study. GOCS (Gynecological Oncology Cooperative Study).

    Science.gov (United States)

    Lorusso, V; Leone, B; Di Vagno, G; Manzione, L; Palmeri, S; Vallejo, C; Machiavelli, M; Nacci, G; Bilancia, D; Leonardi, V; Catino, A; Gargano, G; Loverro, G; Selvaggi, L; De Lena, M

    1998-02-01

    Because of the relative lack of overlapping toxicity, carboplatin (PPL) and cisplatin (CDDP) can be easily combined for treatment of ovarian cancer to increase total platinum dose intensity. Ifosfamide (IFO), one of the most effective single agents in ovarian cancer, has a low hematological toxicity when administered in continuous infusion. From January 1991 to December 1993, 34 patients with advanced ovarian cancer, previously untreated with chemo- or radiotherapy, were enrolled in a phase I-II study with the aim of determining the maximum tolerated dose (MTD) of CDDP (on day 8 of a 28-day cycle) in combination with PPL (300 mg/m2 on day 1) and IFO (4,000 mg/m2/24 h by continuous infusion on day 1). The initial dose level of CDDP was 40 mg/m2, which was continuously increased by 10 mg/m2 up to the MTD defined as one dose level below that inducing dose-limiting toxicity (DLT) in at least two-thirds of treated patients; no dose escalation was allowed in the same patient. Grade 3-4 leukopenia and thrombocytopenia were observed in 54 and 49% of patients, respectively. The DLT was reached at 70 mg/m2 and therefore the dose recommended for the phase II study was 60 mg/m2. Complete (CR) plus partial response was observed in 88% of patients with a 21% pathological CR. With a minimum follow-up of 32 months (median 40 months), median progression-free survival and overall survival were 21 and 39 months, respectively. In conclusion, the combination of CDDP, PPL, and IFO provides an effective regimen for ovarian cancer with an acceptable toxicity profile.

  10. Laparoscopy and computed tomography imaging in advanced ovarian tumors: A roadmap for prediction of optimal cytoreductive surgery

    OpenAIRE

    Ahmed Samy El-Agwany

    2018-01-01

    Introduction: Comprehensive staging laparotomy and cytoreductive surgery followed by chemotherapy has been the standard of care in advanced ovarian cancer. Neoadjuvant chemotherapy is an alternative in inoperable advanced cases. To select patients amenable for successful cytoreduction, major determinants including CT imaging and laparoscopy could be of value. There is no general accepted model for selection and reproducibility of techniques are a major challenge due to different clinical prac...

  11. The Potential Role of the Proteases Cathepsin D and Cathepsin L in the Progression and Metastasis of Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Md Zahidul Islam Pranjol

    2015-11-01

    Full Text Available Epithelial ovarian cancer (EOC is the leading cause of death from gynecologic malignancies and has a poor prognosis due to relatively unspecific early symptoms, and thus often advanced stage, metastasized cancer at presentation. Metastasis of EOC occurs primarily through the transcoelomic route whereby exfoliated tumor cells disseminate within the abdominal cavity, particularly to the omentum. Primary and metastatic tumor growth requires a pool of proangiogenic factors in the microenvironment which propagate new vasculature in the growing cancer. Recent evidence suggests that proangiogenic factors other than the widely known, potent angiogenic factor vascular endothelial growth factor may mediate growth and metastasis of ovarian cancer. In this review we examine the role of some of these alternative factors, specifically cathepsin D and cathepsin L.

  12. The Potential Role of the Proteases Cathepsin D and Cathepsin L in the Progression and Metastasis of Epithelial Ovarian Cancer.

    Science.gov (United States)

    Pranjol, Md Zahidul Islam; Gutowski, Nicholas; Hannemann, Michael; Whatmore, Jacqueline

    2015-11-20

    Epithelial ovarian cancer (EOC) is the leading cause of death from gynecologic malignancies and has a poor prognosis due to relatively unspecific early symptoms, and thus often advanced stage, metastasized cancer at presentation. Metastasis of EOC occurs primarily through the transcoelomic route whereby exfoliated tumor cells disseminate within the abdominal cavity, particularly to the omentum. Primary and metastatic tumor growth requires a pool of proangiogenic factors in the microenvironment which propagate new vasculature in the growing cancer. Recent evidence suggests that proangiogenic factors other than the widely known, potent angiogenic factor vascular endothelial growth factor may mediate growth and metastasis of ovarian cancer. In this review we examine the role of some of these alternative factors, specifically cathepsin D and cathepsin L.

  13. Ovarian preservation in locally advanced cervical cancer undergoing neoadjuvant chemotherapy and radical surgery: our experience and analysis of the literature.

    Science.gov (United States)

    Signorelli, Mauro; Bogani, Giorgio; Chiappa, Valentina; Ditto, Antonino; Scaffa, Cono; Martinelli, Fabio; Lorusso, Domenica; Raspagliesi, Francesco

    2018-03-30

    The aim of this study was to estimate the rate of ovarian metastases and recurrences among patients affected by locally advanced stage cancer patients (LACC), undergoing neoadjuvant chemotherapy (NACT) and radical surgery with conservation of ovaries. Retrospective evaluation of consecutive patients affected by LACC (stage IB2- IIB), treated by NACT followed by radical surgery at National Cancer Institute, Milan, Italy, between 1990-2015. Overall, 331 patients were included. Stage at presentation included stage IB2, IIA and IIB in 120 (36.3%), 63 (19%) and 148 (44.7%) patients, respectively. Main histotype was squamous cell carcinoma (n=265, 80.1%) followed by adenocarcinoma/adenosquamous (n=51, 15.4%), and more than half of patients had a grade 3 carcinoma . Overall, 102 (30.8%) women had at least one ovary preserved during surgery, while 229 (69.2%) had bilateral salpingo-oophorectomy. Comparing patients who had ovarian preservation with patients who had not, we observed that the two groups were comparable in terms of baseline characteristics. Survival outcomes were not influenced by ovarian preservation (disease-free (p=0.93) and overall (p=0.65) survivals). One (1%) woman had a localized ovarian recurrence. Our data suggest that ovarian preservation at the time of surgery is a safe option among women with LACC after NACT with no detrimental impact on oncologic outcome. Further prospective studies are warranted.

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

    International Nuclear Information System (INIS)

    Furuya, Mitsuko

    2012-01-01

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

  15. 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.

  16. Being treated in higher volume hospitals leads to longer progression-free survival for epithelial ovarian carcinoma patients in the Rhone-Alpes region of France

    OpenAIRE

    Huguet, Marius; Perrier, Lionel; Bally, Olivia; Benayoun, David; De Saint Hilaire, Pierre; Beal Ardisson, Dominique; Morelle, Magali; Havet, Nathalie; Joutard, Xavier; Meeus, Pierre; Gabelle, Philippe; Provençal, Jocelyne; Chauleur, Céline; Glehen, Olivier; Charreton, Amandine

    2018-01-01

    Background To investigate the relationship between hospital volume activities and the survival for Epithelial Ovarian Carcinoma (EOC) patients in France. Methods This retrospective study using prospectively implemented databases was conducted on an exhaustive cohort of 267 patients undergoing first-line therapy during 2012 in the Rhone-Alpes Region of France. We compared Progression-Free Survival for Epithelial Ovarian Carcinoma patients receiving first-line therapy in high- (i.e. ≥ 12 cases/...

  17. Prognostic value of miliary versus non-miliary sub-staging in advanced ovarian cancer.

    Science.gov (United States)

    Eng, Kevin H; Morrell, Kayla; Starbuck, Kristen; Spring-Robinson, Chandra; Khan, Aalia; Cleason, Dana; Akman, Levent; Zsiros, Emese; Odunsi, Kunle; Szender, J Brian

    2017-07-01

    The presence of miliary disease during initial ovarian cancer debulking may reflect a distinct mode of peritoneal spread independent from size-based tumor staging and may explain variation in response to treatment and survival outcomes. To infer the prevalence, presentation and clinical implications of miliary disease we reviewed existing surgical records. Reports were available for 1008 primary debulking surgeries for ovarian, primary peritoneal or fallopian tube cancer between 2001 and 2015 (685 reports from 2005 to 2015). Clinical outcome data was available for 938 patients. We analyzed a high-stage sub-cohort for survival (N=436). Most records were evaluable for miliary disease (761/938); for these, the miliary phenotype was highly prevalent (249/761, 32.7%) and often accompanied by ascites (185/249, 74%). While optimal debulking rates were unaffected by miliary disease, total resection (R0) rates were poorer. Liver, stomach, spleen or bladder appeared to be sporadically involved while the omentum, mesentery, bowel, peritoneum and diaphragm were affected simultaneously (Spearman rho>0.5). Overall, miliary disease was associated with worse progression free survival, overall survival, and time from relapse to death independent of stage. Survival effects were particularly strong for Stage IV disease where median overall survival varied by over 30months (log-rank p=0.002). Miliary disease is an identifiable surgical phenotype reflecting a distinct clinical trajectory that adds prognostic information to standard disease burden-based staging. These findings should permit further retrospective investigation in a wider cohort and prompt the consideration of prospective structured operative reporting standards and treatment strategies. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Initial incomplete surgery modifies prognosis in advanced ovarian cancer regardless of subsequent management.

    Science.gov (United States)

    Bacalbasa, Nicolae; Balescu, Irina; Dima, Simona; Herlea, Vlad; David, Leonard; Brasoveanu, Vladislav; Popescu, Irinel

    2015-04-01

    Prognosis in ovarian cancer is determined by completeness of cytoreduction and proper management by specialized oncological gynecologists. Incomplete initial debulking surgery in non-specialized Centers is, however, a reality and there is ongoing discussion about the best subsequent management of such patients. Patients with advanced ovarian cancer (International Federation of Gynecology and Obstetrics--FIGO FIGO stages IIIC-IV) who had biopsy by laparotomy or incomplete cytoreduction followed or not by chemotherapy further referred to our Institution between January 2002 and May 2014 were included. The two groups of incomplete cytoreduction [followed by upfront surgery or followed by chemotherapy and interval debulking surgery (IDS)] were compared and also compared against a cohort of 197 patients with similar characteristics who underwent upfront maximal surgery according to the standard at our Iinstitution during the same period. A total of 99 eligible patients were identified. Sixty-seven of them underwent biopsies by laparotomy and 32 underwent incomplete cytoreduction in other institutions. Twenty-eight patients underwent direct re-operation while 71 patients underwent neoadjuvant chemotherapy followed by IDS. The mean overall survival duration for patients with upfront reoperation was 31 months and 54 months for patients with neoadjuvant chemotherapy and IDS, considerably lower than the 72 months obtained for the group of 197 patients with maximal up-front complete cytoreduction at our Institution. Primary biopsy or incomplete cytoreduction reduces survival regardless of the subsequent approach. However, if incomplete cytoreduction has occurred, neoadjuvant chemotherapy followed by IDS is preferable to up-front reoperation. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  19. A multicenter phase II study of carboplatin in advanced ovarian carcinoma: final report.

    Science.gov (United States)

    Kjorstad, K; Harris, A; Bertelsen, K; Slevin, M; Schultz, H; Hellman, K; Janssens, N; Martin, A; Canetta, R

    1992-03-01

    A phase II trial of single-agent carboplatin in advanced ovarian cancer was performed by 19 institutions from 10 European countries. A total of 260 patients were treated, with a median age of 55 (range: 20-79) years. Karnofsky performance status was 80-100 in about two-thirds of the patients. Prior therapy consisted of surgery only in 31 patients, irradiation in 9, chemotherapy without cisplatin in 45, and with cisplatin in 175. Carboplatin was administered as second-line therapy in about one-half and as third-line or more in one additional third of the study population. Initial dose was 400 mg/m2 in 90, 360 mg/m2 in 152, and 320 mg/m2 or less in 18 patients. A total of 971 courses (mean 3.7, median 2, range: 1-13) of therapy were administered. A total of 16 complete and 46 partial responses were observed in 226 evaluable patients, for an objective response rate of 27%. Efficacy was greater in chemotherapy-untreated patients (51% vs. 23%, p = 0.002). In cisplatin-pretreated patients activity was significantly higher in non-refractory patients (26% vs. 4%, p = 0.015). Myelosuppression was the most significant side effect. However, low hematologic counts seldom translated into clinically significant complications. Patients with impaired baseline creatinine clearance and poor performance status were at higher risk of developing severe myelosuppression during the initial course of treatment. Non hematologic side effects were rare and mild, except for emesis. Carboplatin has a definite role in the treatment of ovarian cancer, but almost complete cross-resistance with the parent compound was observed clinically.

  20. Is intraperitoneal chemotherapy still an acceptable option in primary adjuvant chemotherapy for advanced ovarian cancer?

    Science.gov (United States)

    Monk, B J; Chan, J K

    2017-11-01

    The role of intraperitoneal (i.p.) chemotherapy in treating newly diagnosed advanced epithelial ovarian cancer (EOC) has been the subject of controversy for almost three decades. Three large intergroup phase III trials (GOG 104, 114, 172) have demonstrated a survival benefit associated with i.p. over intravenous (i.v.) therapy in advanced, low-volume EOC. Despite the positive clinical trial results and a subsequent National Cancer Institute alert in 2006, i.p. treatment has not been widely accepted as the standard of care in the United States and is infrequently used in Europe. The hesitancy of clinicians to use i.p. therapy is likely attributed to higher toxicity, inconvenience, catheter complications, and clinical trial design issues. On the other hand, In a long-term follow-up report from these trials, we showed that the effect of i.p. chemotherapy extends beyond 10 years and that the more cycles of i.p. therapy portends for improved survival over similar cycles of i.v. therapy with younger patients having a higher likelihood of completing 6 cycles of i.p. More recently, a fourth randomized phase III trial, GOG 252, failed to show a survival advantage associated with i.p. cisplatin and i.p. carboplatin over dose-dense i.v. paclitaxel and carboplatin. Since the use of bevacizumab was incorporated in all arms of the study, this anti-vascular agent may have equalized or negated the clinical advantage of i.p. chemotherapy and dose-dense weekly as suggested in GOG 262. We are awaiting the results of the Asian iPocc trial comparing dose-dense paclitaxel to i.p. chemotherapy without bevacizumab, though the differences in the tumor histology and pharmacokinetics in Asian versus non-Asian patients may influence the interpretation of the results worldwide. In this review, we review the polarizing opinions on the relevance of i.p. therapy in today's clinical armamentarium. Never before, have oncologists examined the same datasets with divergent conclusions. This topic is

  1. Prognosis for advanced-stage primary peritoneal serous papillary carcinoma and serous ovarian cancer in Taiwan.

    Science.gov (United States)

    Chao, Kuan-Chong; Chen, Yi-Jen; Juang, Chi-Mou; Lau, Hei-Yu; Wen, Kuo-Chang; Sung, Pi-Lin; Fang, Feng-Ying; Twu, Nae-Fang; Yen, Ming-Shyen

    2013-03-01

    To compare the prognosis of patients with advanced-stage primary peritoneal serous papillary carcinoma (PSPC) or papillary serous ovarian cancer (PSOC). This was a retrospective case-control study and included two study groups: one with stage III/IV PSPC (n = 38) patients and the other with PSOC (n = 53) patients. Patients were matched for histologic subtype (serous tumor), tumor stage, tumor grade, residual disease at the end of debulking surgery (primary or interval), and age (±5 years). Mean age was significantly greater for patients with PSPC (63.03 ± 11.88 years) than for patients with PSOC (55.92 ± 12.56 years, p = 0.008). Optimal debulking surgery was performed initially in 71.9% of PSPC patients and 66.0% of PSOC patients. In addition, 93.9% of PSPC patients and 92.3% of PSOC patients were treated with platinum-paclitaxel chemotherapy. The frequency of high-grade tumors was significantly higher in the PSPC (100%) than in the PSOC group (68.3%; p statistic). PFS was similar for advanced-stage PSPC and PSOC patients. Since the PSPC patients tended to be older and have more high-grade tumors, OS was shorter for PSPC than for POSC patients. Thus, management of the two types of cancer should not differ. Copyright © 2013. Published by Elsevier B.V.

  2. State of development progress of advanced boiling water reactors

    International Nuclear Information System (INIS)

    Tomono, Katsuya

    1982-01-01

    Advanced BWRs being developed at present are those aiming at the improvement of reliability and safety, the reduction of radiation exposure, the improvement of operation performance and capacity ratio of plants, and the heightening of economical efficiency by concentrating the experience and excellent technology of BWR manufacturers in the world. Now in Japan, the independence with Japanese technology is possible in almost all fields of nuclear power generation, and the improvement and standardization project is in progress to obtain the steady results. However, in order to pursue the most desirable BWRs conceivable at present, five BWR manufacturers in the world organized the Advanced Engineering Team in July, 1978, and performed the feasibility study of advanced BWRs for more than one year. Tokyo Electric Power Co., Inc., evaluated the report on the results, and judged that it is desirable to advance into the next stage aiming at the practical use of advanced BWRs. For the purpose, the electric power common research on advanced BWRs has been in progress, and the A-BWR project is to be examined in the third improvement and standardization project of MITI. The main technical features such as the coolant recirculation system of internal pump type, reinforced concrete containment vessels, fine motion control rod drive, improved core and fuel and others are explained. (Kako, I.)

  3. Gene expression of membrane transporters: Importance for prognosis and progression of ovarian carcinoma

    Czech Academy of Sciences Publication Activity Database

    Elsnerová, K.; Mohelniková; Duchonová, B.; Čeřovská, E.; Ehrlichová, M.; Gut, I.; Rob, L.; Skapa, P.; Hruda, M.; Bartáková, A.; Bouda, J.; Vodička, Pavel; Souček, P.; Václavíková, R.

    2016-01-01

    Roč. 35, č. 4 (2016), s. 2159-2170 ISSN 1021-335X R&D Projects: GA MZd(CZ) NT14056; GA MŠk(CZ) LD14050 Institutional support: RVO:68378041 Keywords : epithelial ovarian cancer * ABC transporters * SLC transporters * gene expression * prognosis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.662, year: 2016

  4. ABCB1 (MDR1) polymorphisms and ovarian cancer progression and survival

    DEFF Research Database (Denmark)

    Johnatty, Sharon E; Beesley, Jonathan; Gao, Bo

    2013-01-01

    ABCB1 encodes the multi-drug efflux pump P-glycoprotein (P-gp) and has been implicated in multi-drug resistance. We comprehensively evaluated this gene and flanking regions for an association with clinical outcome in epithelial ovarian cancer (EOC)....

  5. Imatinib Mesylate in Treating Patients With Progressive, Refractory, or Recurrent Stage II or Stage III Testicular or Ovarian Cancer

    Science.gov (United States)

    2013-01-15

    Ovarian Dysgerminoma; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Ovarian Germ Cell Tumor; Stage II Malignant Testicular Germ Cell Tumor; Stage II Ovarian Germ Cell Tumor; Stage III Malignant Testicular Germ Cell Tumor; Stage III Ovarian Germ Cell Tumor; Testicular Seminoma

  6. Effectiveness of tranexamic acid in reducing blood loss during cytoreductive surgery for advanced ovarian cancer.

    Science.gov (United States)

    Kietpeerakool, Chumnan; Supoken, Amornrat; Laopaiboon, Malinee; Lumbiganon, Pisake

    2016-01-23

    Ovarian cancer is the third most common gynaecological cancer worldwide, with an age-standardised incidence rate of 6.1 per 10,000 women. Standard therapy for advanced epithelial ovarian cancer (EOC) includes a combination of cytoreductive surgery and platinum-based chemotherapy. Cytoreductive surgery aims to remove as much of the visible tumour as possible. As extensive intraperitoneal metastases are typical of advanced EOC, cytoreductive surgery is usually an extensive procedure with the risk of excessive bleeding. Tranexamic acid given perioperatively is effective in reducing blood loss and allogeneic blood transfusion requirements in a variety of surgical settings. Therefore, tranexamic acid seems to be a promising agent for minimising blood loss and the need for blood transfusion among women with advanced EOC undergoing cytoreductive surgery. To assess the effects of tranexamic acid for reducing blood loss associated with cytoreductive surgery in women with advanced EOC (stage III to IV). We searched the Cochrane Gynaecological, Neuro-oncology and Orphan Cancers Trial Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 5, 2015), MEDLINE, EMBASE and conference proceedings to May 2015. We also checked registers of clinical trials, citation lists of included studies, key textbooks and previous systematic reviews for potentially relevant studies. We included randomised controlled trials (RCTs) comparing tranexamic acid given during surgery versus placebo or no treatment, in adult women diagnosed with advanced EOC. Two review authors (CK, AS) independently selected potentially relevant trials, extracted data, assessed risk of bias, compared results and resolved disagreements by discussion. We found only one study that met our inclusion criteria. This was a randomised double blind, placebo-controlled multicentre study conducted to evaluate the effectiveness of a single dose of intravenous tranexamic acid (15 mg/kg body weight) versus

  7. Prediction of 30-day morbidity after primary cytoreductive surgery for advanced stage ovarian cancer.

    Science.gov (United States)

    Gerestein, C G; Nieuwenhuyzen-de Boer, G M; Eijkemans, M J; Kooi, G S; Burger, C W

    2010-01-01

    Treatment in advanced stage epithelial ovarian cancer (EOC) is based on primary cytoreductive surgery followed by platinum-based chemotherapy. Successful cytoreduction to minimal residual tumour burden is the most important determinant of prognosis. However, extensive surgical procedures to achieve maximal debulking are inevitably associated with postoperative morbidity and mortality. The objective of this study is to determine predictors of 30-day morbidity after primary cytoreductive surgery for advanced stage EOC. All patients in the South Western part of the Netherlands who underwent primary cytoreductive surgery for advanced stage EOC between January 2004 and December 2007 were identified from the Rotterdam Cancer Registry database. All peri- and postoperative complications within 30 days after surgery were registered and classified according to the definitions of the National Surgical Quality Improvement Programme (NSQIP). To investigate independent predictors of 30-day morbidity, a Cox proportional hazards model with backward stepwise elimination was utilised. The identified predictors were entered into a nomogram. Two hundred and ninety-three patients entered the study protocol. Optimal cytoreduction was achieved in 136 (46%) patients. 30-day morbidity was seen in 99 (34%) patients. Postoperative morbidity could be predicted by age (P=0.007; odds ratio [OR] 1.034), WHO performance status (P=0.046; OR 1.757), extent of surgery (P=0.1308; OR=2.101), and operative time (P=0.017; OR 1.007) with an optimism corrected c-statistic of 0.68. 30-day morbidity could be predicted by age, WHO performance status, operative time and extent of surgery. The generated nomogram could be valuable for predicting operative risk in the individual patient.

  8. Nomogram for suboptimal cytoreduction at primary surgery for advanced stage ovarian cancer.

    Science.gov (United States)

    Gerestein, Cornelis G; Eijkemans, Marinus J; Bakker, Jeanette; Elgersma, Otto E; van der Burg, Maria E L; Kooi, Geertruida S; Burger, Curt W

    2011-11-01

    Maximal cytoreduction to minimal residual tumor is the most important determinant of prognosis in patients with advanced stage epithelial ovarian cancer (EOC). Preoperative prediction of suboptimal cytoreduction, defined as residual tumor >1 cm, could guide treatment decisions and improve counseling. The objective of this study was to identify predictive computed tomographic (CT) scan and clinical parameters for suboptimal cytoreduction at primary cytoreductive surgery for advanced stage EOC and to generate a nomogram with the identified parameters, which would be easy to use in daily clinical practice. Between October 2005 and December 2008, all patients with primary surgery for suspected advanced stage EOC at six participating teaching hospitals in the South Western part of the Netherlands entered the study protocol. To investigate independent predictors of suboptimal cytoreduction, a Cox proportional hazard model with backward stepwise elimination was utilized. One hundred and fifteen patients with FIGO stage III/IV EOC entered the study protocol. Optimal cytoreduction was achieved in 52 (45%) patients. A suboptimal cytoreduction was predicted by preoperative blood platelet count (p=0.1990; odds ratio (OR)=1.002), diffuse peritoneal thickening (DPT) (p=0.0074; OR=3.021), and presence of ascites on at least two thirds of CT scan slices (p=0.0385; OR=2.294) with a for-optimism corrected c-statistic of 0.67. Suboptimal cytoreduction was predicted by preoperative platelet count, DPT and presence of ascites. The generated nomogram can, after external validation, be used to estimate surgical outcome and to identify those patients, who might benefit from alternative treatment approaches.

  9. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for the treatment of advanced epithelial and recurrent ovarian carcinoma: a single center experience.

    Science.gov (United States)

    Pavlov, Maja J; Ceranic, Miljan S; Latincic, Stojan M; Sabljak, Predrag V; Kecmanovic, Dragutin M; Sugarbaker, Paul H

    2017-09-07

    With standard treatment of epithelial ovarian cancer (EOC), prognosis is very poor. The aim of this study is to show early and late results in patients who underwent cytoreductive surgery and intraperitoneal chemotherapy. This was a retrospective single centre study. All patients with advanced and recurrent ovarian cancer treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) or modified early postoperative intraperitoneal chemotherapy (EPIC) were included in the study. In the period 1995-2014, 116 patients were treated, 55 with primary EOC and 61 with recurrent EOC. The mean age was 59 years (26-74). Statistically, median survival time was significantly longer in the group with primary advanced cancer of the ovary (41.3 months) compared to relapsed ovarian cancer (27.3 months). Survival for the primary EOC was 65 and 24% at 3 and 5 years, respectively. Survival for recurrent EOC was 33 and 16% at 3 and 5 years, respectively. Mortality was 1/116 (0.8%). Morbidity was 11/116 (9.5%). Peritoneal cancer index (PCI) was ≤20 in 59 (51%) patients and statistically, their average survival was significantly longer than in the group of 57 (49%) patients with PCI >20 (p = 0.014). In advanced or recurrent EOC, a curative therapeutic approach was pursued that combined optimal cytoreductive surgery and intraperitoneal chemotherapy. PCI and timing of the intervention (primary or recurrent) were the strongest independent prognostic factors.

  10. Shifting paradigms in diminished ovarian reserve and advanced reproductive age in assisted reproduction: customization instead of conformity.

    Science.gov (United States)

    Reed, Beverly G; Babayev, Samir N; Bukulmez, Orhan

    2015-05-01

    As women are increasingly delaying childbearing into their 30s and beyond, diminished ovarian reserve (DOR) and advanced reproductive age (ARA) patients are bound to become a large proportion of all assisted reproductive technology practices. Traditional controlled ovarian stimulation (COS) protocols for DOR and/or ARA have had some limited success, but pregnancy rates are lower and cycle cancellation rates are higher than their younger counterparts with normal ovarian reserve. Though many physicians have a selection of favorite standard protocols that they use, patients with DOR may require closer monitoring and customization of the treatment cycle to address the common problems that come with low ovarian reserve. Frequent issues that surface in women with DOR and/or ARA include poor follicular response, premature luteinizing hormone surge, and poor embryo quality. Limited published evidence exists to guide treatment for DOR. However, use of minimal or mild doses of gonadotropins, avoidance of severe pituitary suppression, and consideration for luteal phase stimulation and a "freeze all" approach are possible customized treatment options that can be considered for such patients who have failed more traditional COS protocols. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  11. The adhesion molecule NCAM promotes ovarian cancer progression via FGFR signalling

    DEFF Research Database (Denmark)

    Zecchini, Silvia; Bombardelli, Lorenzo; Decio, Alessandra

    2011-01-01

    glycoprotein involved in brain development and plasticity, in EOC. NCAM is absent from normal ovarian epithelium but becomes highly expressed in a subset of human EOC, in which NCAM expression is associated with high tumour grade, suggesting a causal role in cancer aggressiveness. We demonstrate that NCAM......Epithelial ovarian carcinoma (EOC) is an aggressive neoplasm, which mainly disseminates to organs of the peritoneal cavity, an event mediated by molecular mechanisms that remain elusive. Here, we investigated the expression and functional role of neural cell adhesion molecule (NCAM), a cell surface...... stimulates EOC cell migration and invasion in vitro and promotes metastatic dissemination in mice. This pro-malignant function of NCAM is mediated by its interaction with fibroblast growth factor receptor (FGFR). Indeed, not only FGFR signalling is required for NCAM-induced EOC cell motility, but targeting...

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

    DEFF Research Database (Denmark)

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

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Arash Rafii

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

  14. Lack of relationship between TIMP-1 tumour cell immunoreactivity, treatment efficacy and prognosis in patients with advanced epithelial ovarian cancer

    DEFF Research Database (Denmark)

    Steffensen, Karina Dahl; Waldstrøm, Marianne; Christensen, Rikke Kølby

    2010-01-01

    BACKGROUND: Tissue inhibitor of metalloproteinase 1 (TIMP-1) is a natural inhibitor of the matrix metalloproteinases (MMPs) which are proteolytic enzymes involved in degradation of extracellular matrix thereby favoring tumour cell invasion and metastasis. TIMP-1 activity in tumour tissue may ther...... immunoreactivity in tumour tissue from patients with primary epithelial ovarian cancer did not correlate with patient survival or response to combination platinum/cyclophosphamide therapy.......BACKGROUND: Tissue inhibitor of metalloproteinase 1 (TIMP-1) is a natural inhibitor of the matrix metalloproteinases (MMPs) which are proteolytic enzymes involved in degradation of extracellular matrix thereby favoring tumour cell invasion and metastasis. TIMP-1 activity in tumour tissue may...... therefore play an essential role in the progression of a malignant tumour.The primary aim of the present study was to evaluate TIMP-1 protein immunoreactivity in tissue from primary ovarian cancer patients and associate these findings with the course of the disease including response to treatment...

  15. Optimal debulking targets in women with advanced stage ovarian cancer: a retrospective study of immediate versus interval debulking surgery.

    Science.gov (United States)

    Altman, Alon D; Nelson, Gregg; Chu, Pamela; Nation, Jill; Ghatage, Prafull

    2012-06-01

    The objective of this study was to examine both overall and disease-free survival of patients with advanced stage ovarian cancer after immediate or interval debulking surgery based on residual disease. We performed a retrospective chart review at the Tom Baker Cancer Centre in Calgary, Alberta of patients with pathologically confirmed stage III or IV ovarian cancer, fallopian tube cancer, or primary peritoneal cancer between 2003 and 2007. We collected data on the dates of diagnosis, recurrence, and death; cancer stage and grade, patients' age, surgery performed, and residual disease. One hundred ninety-two patients were included in the final analysis. The optimal debulking rate with immediate surgery was 64.8%, and with interval surgery it was 85.9%. There were improved overall and disease-free survival rates for optimally debulked disease (advanced stage ovarian cancer, the goal of surgery should be resection of disease to microscopic residual at the initial procedure. This results in improved overall survival than lesser degrees of resection. Further studies are required to determine optimal surgical management.

  16. Complete resection of locally advanced ovarian carcinoma fixed to the pelvic sidewall and involving external and internal iliac vessels.

    Science.gov (United States)

    Nishikimi, Kyoko; Tate, Shinichi; Matsuoka, Ayumu; Shozu, Makio

    2017-08-01

    Locally advanced ovarian carcinomas may be fixed to the pelvic sidewall, and although these often involve the internal iliac vessels, they rarely involve the external iliac vessels. Such tumors are mostly considered inoperable. We present a surgical technique for complete resection of locally advanced ovarian carcinoma fixed to the pelvic sidewall and involving external and internal iliac vessels. A 69-year-old woman presented with ovarian carcinoma fixed to the right pelvic sidewall, which involved the right external and internal iliac arteries and veins and the right lower ureter, rectum, and vagina. We cut the external iliac artery and vein at the bifurcation and at the inguinal ligament to resect the external artery and vein. Then, we reconstructed the arterial and venous supplies of the right external artery and vein with grafts. After creating a wide space immediately inside of the sacral plexus to allow the tumor fixed to pelvic sidewall with the internal iliac vessels to move medially, we performed total internal iliac vessel resection. We achieved complete en bloc tumor resection with the right external and internal artery and vein, right ureter, vagina, and rectum adhering to the tumor. There were no intra- or postoperative complications, such as bleeding, graft occlusion, infection, or limb edema. Exfoliation from the sacral plexus and total resection with external and internal iliac vessels enables complete resection of the tumor fixed to the pelvic sidewall. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Avinash Pandey

    2016-01-01

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

  18. High-volume ovarian cancer care: survival impact and disparities in access for advanced-stage disease.

    Science.gov (United States)

    Bristow, Robert E; Chang, Jenny; Ziogas, Argyrios; Randall, Leslie M; Anton-Culver, Hoda

    2014-02-01

    To characterize the impact of hospital and physician ovarian cancer case volume on survival for advanced-stage disease and investigate socio-demographic variables associated with access to high-volume providers. Consecutive patients with stage IIIC/IV epithelial ovarian cancer (1/1/96-12/31/06) were identified from the California Cancer Registry. Disease-specific survival analysis was performed using Cox-proportional hazards model. Multivariate logistic regression analyses were used to evaluate for differences in access to high-volume hospitals (HVH) (≥20 cases/year), high-volume physicians (HVP) (≥10 cases/year), and cross-tabulations of high- or low-volume hospital (LVH) and physician (LVP) according to socio-demographic variables. A total of 11,865 patients were identified. The median ovarian cancer-specific survival for all patients was 28.2 months, and on multivariate analysis the HVH/HVP provider combination (HR = 1.00) was associated with superior ovarian cancer-specific survival compared to LVH/LVP (HR = 1.31, 95%CI = 1.16-1.49). Overall, 2119 patients (17.9%) were cared for at HVHs, and 1791 patients (15.1%) were treated by HVPs. Only 4.3% of patients received care from HVH/HVP, while 53.1% of patients were treated by LVH/LVP. Both race and socio-demographic characteristics were independently associated with an increased likelihood of being cared for by the LVH/LVP combination and included: Hispanic race (OR = 1.72, 95%CI = 1.22-2.42), Asian/Pacific Islander race (OR = 1.57, 95%CI = 1.07-2.32), Medicaid insurance (OR = 2.51, 95%CI = 1.46-4.30), and low socioeconomic status (OR = 2.84, 95%CI = 1.90-4.23). Among patients with advanced-stage ovarian cancer, the provider combination of HVH/HVP is an independent predictor of improved disease-specific survival. Access to high-volume ovarian cancer providers is limited, and barriers are more pronounced for patients with low socioeconomic status, Medicaid insurance, and racial minorities. Copyright © 2013

  19. Advanced teaching labs in physics - celebrating progress; challenges ahead

    Science.gov (United States)

    Peterson, Richard

    A few examples of optical physics experiments may help us first reflect on significant progress on how advanced lab initiatives may now be more effectively developed, discussed, and disseminated - as opposed to only 10 or 15 years back. Many cooperative developments of the last decade are having profound impacts on advanced lab workers and students. Central to these changes are the programs of the Advanced Laboratory Physics Association (ALPhA) (Immersions, BFY conferences), AAPT (advlab-l server, ComPADRE, apparatus competitions, summer workshops/sessions), APS (Reichert Award, FEd activities and sessions), and the Jonathan F. Reichert Foundation (ALPhA support and institution matched equipment grants for Immersion participants). Broad NSF support has helped undergird several of these initiatives. Two of the most significant challenges before this new advanced lab community are (a) to somehow enhance funding opportunities for teaching equipment and apparatus in an era of minimal NSF equipment support, and (b) to help develop a more complementary relationship between research-based advanced lab pedagogies and the development of fresh physics experiments that help enable the mentoring and experimental challenge of our students.

  20. Annexin A4 fucosylation enhances its interaction with the NF-kB p50 and promotes tumor progression of ovarian clear cell carcinoma.

    Science.gov (United States)

    Wang, Huimin; Deng, Lu; Cai, Mingbo; Zhuang, Huiyu; Zhu, Liancheng; Hao, Yingying; Gao, Jian; Liu, Juanjuan; Li, Xiao; Lin, Bei

    2017-12-08

    To study the structural relationship between annexin A4 and the Lewis y antigen and compare their expression and significance in ovarian clear cell carcinoma, and to explore how annexin A4 fucose glycosylation effects the interaction between annexin A4 and NF-kB p50, and how it promotes tumour progression of ovarian clear cell carcinoma. Structural relationships between annexin A4 and Lewis y antigen were detected using immunoprecipitation. Annexin A4 and Lewis y antigen expression in various subtypes of ovarian cancer tissues was detected by immunohistochemistry, and the relation between their expression was examined. Any interactions between annexin A4 and NF-kB p50 in ovarian clear cell carcinoma were detected by co-immunoprecipitation. Then looked for changes in expression of Lewis y antigen, annexin A4, NF-kB p50 and a number of downstream related molecules before and after transfection annexin A4 or FUT1, and also analyzed changes in biological processes. Lewis y antigen is a part of annexin A4 structure. The expression rate of both annexin A4 and Lewis y antigen was significantly higher in ovarian clear cell carcinoma than in other subtypes of epithelial ovarian cancer, and are associated with the clinical stages, chemotherapy resistance and poor prognostic. The interaction between annexin A4 and NF-kB p50 promoted cell proliferation, adhesion, invasion, metastasis ability and autophagy, and inhibits apoptosis, Lewis y enhanced this interaction. Annexin A4 contains Lewis y structure, Lewis y antigen modification of annexin A4 enhances its interaction with NF-kB p50, which promotes ovarian clear cell carcinoma malignancy progression.

  1. Development of a prediction model for residual disease in newly diagnosed advanced ovarian cancer.

    Science.gov (United States)

    Janco, Jo Marie Tran; Glaser, Gretchen; Kim, Bohyun; McGree, Michaela E; Weaver, Amy L; Cliby, William A; Dowdy, Sean C; Bakkum-Gamez, Jamie N

    2015-07-01

    To construct a tool, using computed tomography (CT) imaging and preoperative clinical variables, to estimate successful primary cytoreduction for advanced epithelial ovarian cancer (EOC). Women who underwent primary cytoreductive surgery for stage IIIC/IV EOC at Mayo Clinic between 1/2/2003 and 12/30/2011 and had preoperative CT images of the abdomen and pelvis within 90days prior to their surgery available for review were included. CT images were reviewed for large-volume ascites, diffuse peritoneal thickening (DPT), omental cake, lymphadenopathy (LP), and spleen or liver involvement. Preoperative factors included age, body mass index (BMI), Eastern Cooperative Oncology Group performance status (ECOG PS), American Society of Anesthesiologists (ASA) score, albumin, CA-125, and thrombocytosis. Two prediction models were developed to estimate the probability of (i) complete and (ii) suboptimal cytoreduction (residual disease (RD) >1cm) using multivariable logistic analysis with backward and stepwise variable selection methods. Internal validation was assessed using bootstrap resampling to derive an optimism-corrected estimate of the c-index. 279 patients met inclusion criteria: 143 had complete cytoreduction, 26 had suboptimal cytoreduction (RD>1cm), and 110 had measurable RD ≤1cm. On multivariable analysis, age, absence of ascites, omental cake, and DPT on CT imaging independently predicted complete cytoreduction (c-index=0.748). Conversely, predictors of suboptimal cytoreduction were ECOG PS, DPT, and LP on preoperative CT imaging (c-index=0.685). The generated models serve as preoperative evaluation tools that may improve counseling and selection for primary surgery, but need to be externally validated. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Recent Progress in Advanced Materials for Lithium Ion Batteries

    Directory of Open Access Journals (Sweden)

    Jiajun Chen

    2013-01-01

    Full Text Available The development and commercialization of lithium ion batteries is rooted in material discovery. Promising new materials with high energy density are required for achieving the goal toward alternative forms of transportation. Over the past decade, significant progress and effort has been made in developing the new generation of Li-ion battery materials. In the review, I will focus on the recent advance of tin- and silicon-based anode materials. Additionally, new polyoxyanion cathodes, such as phosphates and silicates as cathode materials, will also be discussed.

  3. FY2016 Advanced Batteries R&D Annual Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    None, None

    2017-08-31

    The Advanced Batteries research and development (R&D) subprogram within the DOE Vehicle Technologies Office (VTO) provides support and guidance for projects focusing on batteries for plug-in electric vehicles. Program targets focus on overcoming technical barriers to enable market success including: (1) significantly reducing battery cost, (2) increasing battery performance (power, energy, durability), (3) reducing battery weight & volume, and (4) increasing battery tolerance to abusive conditions such as short circuit, overcharge, and crush. This report describes the progress made on the research and development projects funded by the Battery subprogram in 2016. This section covers the Vehicle Technologies Office overview; the Battery subprogram R&D overview; Advanced Battery Development project summaries; and Battery Testing, Analysis, and Design project summaries. It also includes the cover and table of contents.

  4. The four and a half LIM domains 2 (FHL2) regulates ovarian granulosa cell tumor progression via controlling AKT1 transcription

    OpenAIRE

    Hua, G; He, C; Lv, X; Fan, L; Wang, C; Remmenga, S W; Rodabaugh, K J; Yang, L; Lele, S M; Yang, P; Karpf, A R; Davis, J S; Wang, C

    2016-01-01

    The four and a half LIM domains 2 (FHL2) has been shown to play important roles in the regulation of cell proliferation, survival, adhesion, motility and signal transduction in a cell type and tissue-dependent manner. However, the function of FHL2 in ovarian physiology and pathology is unclear. The aim of this study was to determine the role and functional mechanism of FHL2 in the progression of ovarian granulosa cell tumors (GCTs). Immunohistochemical analysis indicated that FHL2 was overexp...

  5. Expression of the glioma-associated oncogene homolog 1 (gli1 in advanced serous ovarian cancer is associated with unfavorable overall survival.

    Directory of Open Access Journals (Sweden)

    Alessandra Ciucci

    Full Text Available Recent evidence links aberrant activation of Hedgehog (Hh signaling with the pathogenesis of several cancers including medulloblastoma, glioblastoma, melanoma as well as pancreas, colorectal, and prostate carcinomas. Here we investigated the role of the transcription factor Gli1 in ovarian cancer. To this end, the expression profile of Gli1 was examined in normal ovaries, ovarian tumors, and ovarian cancer cell lines, and the in vitro effects of a specific Hh-pathway blocker, KAAD-cyclopamine, or a specific Gli1 inhibitor (GANT58 on cell proliferation and on Hh target gene expression were also assessed. Results obtained showed that epithelial cells in ovarian cancer tissue express significantly higher levels of nuclear Gli1 than in normal ovarian tissue, where the protein was almost undetectable. In addition, multivariate analysis showed that nuclear Gli1 was independently associated to poor survival in advanced serous ovarian cancer patients (HR = 2.2, 95%CI 1.0-5.1, p = 0.04. In vitro experiments demonstrated Gli1 expression in the three ovarian carcinoma cell lines tested, A2780, SKOV-3 and OVCAR-3. Remarkably, although KAAD-cyclopamine led to decreased cell proliferation, this treatment did not inhibit hedgehog target gene expression in any of the three ovarian cancer cell lines, suggesting that the inhibition of cell proliferation was a nonspecific or toxic effect. In line with these data, no differences on cell proliferation were observed when cell lines were treated with GANT58. Overall, our clinical data support the role of Gli1 as a prognostic marker in advanced serous ovarian cancer and as a possible therapeutic target in this disease. However, our in vitro findings draw attention to the need for selection of appropriate experimental models that accurately represent human tumor for testing future therapies involving Hh pathway inhibitors.

  6. Pro-apoptotic activity of new analog of anthracyclines--WP 631 in advanced ovarian cancer cell line.

    Science.gov (United States)

    Gajek, Arkadiusz; Denel, Marta; Bukowska, Barbara; Rogalska, Aneta; Marczak, Agnieszka

    2014-03-01

    In this work we investigated the mode of cell death induced by WP 631, a novel anthracycline antibiotic, in the ovarian cancer cell line (OV-90) derived from the malignant ascites of a patient diagnosed with advanced disease. The effects were compared with those of doxorubicin (DOX), a first generation anthracycline. The ability of WP 631 to induce apoptosis and necrosis was examined by double staining with Annexin V and propidium iodide, measurements of the level of intracellular calcium ions and cytochrome c, PARP cleavage. We also investigated the possible involvement of the caspases activation, DNA degradation (comet assay) and intracellular reactive oxygen species (ROS) production in the development of the apoptotic events and their significance for drug efficiency. The results obtained clearly demonstrate that antiproliferative capacity of WP 631 in tested cell line was a few times greater than that of DOX. Furthermore, ovarian cancer cells treated with WP 631 showed a higher mean level of basal DNA damage in comparison to DOX. In conclusion, WP 631 is able to induce caspase - dependent apoptosis in human ovarian cancer cells. Obtained results suggested that WP 631 may be a candidate for further evaluation as chemotherapeutic agents for human cancers. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Management of advanced ovarian cancer in South West Wales - a comparison between primary debulking surgery and primary chemotherapy treatment strategies in an unselected, consecutive patient cohort.

    Science.gov (United States)

    Drews, F; Bertelli, G; Lutchman-Singh, K

    2017-08-01

    This study represents the first reported outcomes for patients with advanced ovarian cancer (AOC) in South-West Wales undergoing treatment with primary debulking surgery or primary chemotherapy respectively. This is a retrospective study of consecutive, unselected patients with advanced ovarian, fallopian tube or primary peritoneal cancer (FIGO III/IV) presenting to a regional cancer centre between October 2007 and October 2014. Patients were identified from Welsh Cancer Services records and relevant data was extracted from electronic National Health Service (NHS) databases. Main outcome measures were median overall survival (OS), progression free survival (PFS) and perioperative adverse events. Hazard ratio estimation was carried out with Cox Regression analysis and survival determined by Kaplan-Meier plots. Of 220 women with AOC, 32.3% underwent primary debulking surgery (PDS) and 67.7% primary chemotherapy and interval debulking (PCT-IDS). Patients were often elderly (median age 67 years) with a poor performance status (26.5% PS >1). Complete cytoreduction (0cm residual) was achieved in 32.4% of patients in the PDS group and in 50.0% of patients undergoing IDS. Median OS for all patients was 21.9 months (PDS: 27.0 and PCT-IDS: 19.2 months; p >0.05) and median PFS was 13.1 months (PDS: 14.3 months and PCT-IDS: 13.0 months; p >0.05). Median overall and progression free survival for patients achieving complete cytoreduction were 48.0 and 23.2 months respectively in the PDS group and 35.4 months and 18.6 months in the IDS group (p >0.05). This retrospective study of an unselected, consecutive cohort of women with AOC in South West Wales shows comparable survival outcomes with recently published trials, despite the relatively advanced age and poor performance status of our patient cohort. Over the seven-year study period, our data also demonstrated a non-significant trend towards improved survival following primary surgery in patients who achieved maximal

  8. Palbociclib Combined with Fulvestrant in Premenopausal Women with Advanced Breast Cancer and Prior Progression on Endocrine Therapy: PALOMA-3 Results.

    Science.gov (United States)

    Loibl, Sibylle; Turner, Nicholas C; Ro, Jungsil; Cristofanilli, Massimo; Iwata, Hiroji; Im, Seock-Ah; Masuda, Norikazu; Loi, Sherene; André, Fabrice; Harbeck, Nadia; Verma, Sunil; Folkerd, Elizabeth; Puyana Theall, Kathy; Hoffman, Justin; Zhang, Ke; Bartlett, Cynthia Huang; Dowsett, Mitchell

    2017-09-01

    The efficacy and safety of palbociclib, a cyclin-dependent kinase 4/6 inhibitor, combined with fulvestrant and goserelin was assessed in premenopausal women with advanced breast cancer (ABC) who had progressed on prior endocrine therapy (ET). One hundred eight premenopausal endocrine-refractory women ≥18 years with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) ABC were among 521 women randomized 2:1 (347:174) to fulvestrant (500 mg) ± goserelin with either palbociclib (125 mg/day orally, 3 weeks on, 1 week off) or placebo. This analysis assessed whether the overall tolerable safety profile and significant progression-free survival (PFS) improvement extended to premenopausal women. Potential drug-drug interactions (DDIs) and ovarian suppression with goserelin were assessed via plasma pharmacokinetics and biochemical analyses, respectively. (ClinicalTrials.gov identifier: NCT01942135) RESULTS: Median PFS for premenopausal women in the palbociclib ( n  = 72) versus placebo arm ( n  = 36) was 9.5 versus 5.6 months, respectively (hazard ratio, 0.50, 95% confidence interval: 0.29-0.87), and consistent with the significant PFS improvement in the same arms for postmenopausal women. Any-grade and grade ≤3 neutropenia, leukopenia, and infections were among the most frequent adverse events reported in the palbociclib arm with concurrent goserelin administration. Hormone concentrations were similar between treatment arms and confirmed sustained ovarian suppression. Clinically relevant DDIs were not observed. Palbociclib combined with fulvestrant and goserelin was an effective and well-tolerated treatment for premenopausal women with prior endocrine-resistant HR+/HER2- ABC. Inclusion of both premenopausal and postmenopausal women in pivotal combination ET trials facilitates access to novel drugs for young women and should be considered as a new standard for clinical trial design. PALOMA-3, the first registrational

  9. Association of promoter methylation of VGF and PGP9.5 with ovarian cancer progression.

    Directory of Open Access Journals (Sweden)

    Mariana Brait

    Full Text Available To elucidate the role of biological and clinical impact of aberrant promoter hypermethylation (PH in ovarian cancer (OC.PH of PGP9.5, HIC1, AIM1, APC, PAK3, MGMT, KIF1A, CCNA1, ESR1, SSBP2, GSTP1, FKBP4 and VGF were assessed by quantitative methylation specific PCR (QMSP in a training set. We selected two genes (VGF and PGP9.5 for further QMSP analysis in a larger independent validation (IV set with available clinical data. Biologic relevance of VGF gene was also evaluated.PH frequency for PGP9.5 and VGF were 85% (316/372 and 43% (158/366 respectively in the IV set of samples while no PH was observed in controls. In 372 OC cases with available follow up, PGP9.5 and VGF PH were correlated with better patient survival [Hazard Ratios (HR for overall survival (OS were 0.59 (95% Confidence Intervals (CI  = 0.42-0.84, p = 0.004, and 0.73 (95%CI = 0.55-0.97, p = 0.028 respectively, and for disease specific survival (DSS were 0.57 (95%CI 0.39-0.82, p = 0.003 and 0.72 (95%CI 0.54-0.96, p = 0.027. In multivariate analysis, VGF PH remained an independent prognostic factor for OS (HR 0.61, 95%CI 0.43-0.86, p<0.005 and DSS (HR 0.58, 95%CI 0.41-0.83, p<0.003. Furthermore, PGP9.5 PH was significantly correlated with lower grade, early stage tumors, and with absence of residual disease. Forced expression of VGF in OC cell lines inhibited cell growth.Our results indicate that VGF and PGP9.5 PH are potential biomarkers for ovarian carcinoma. Confirmatory cohorts with longitudinal follow-up are required in future studies to define the clinical impact of VGF and PGP9.5 PH before clinical application.

  10. Peripheral neuropathy due to therapy with paclitaxel, gemcitabine, and cisplatin in patients with advanced ovarian cancer.

    NARCIS (Netherlands)

    Verstappen, C.C.P.; Postma, T.J.; Hoekman, K.; Heimans, J.J.

    2003-01-01

    BACKGROUND: To evaluate the peripheral neuropathic changes induced by combination chemotherapy including paclitaxel (taxol), gemcitabine and cisplatin (TGC regimen). PATIENTS AND METHODS: Eighteen patients with primary or recurrent ovarian cancer were treated with paclitaxel 150 or 110 mg/m2,

  11. [The molecular biology of epithelial ovarian cancer].

    Science.gov (United States)

    Leary, Alexandra; Pautier, Patricia; Tazi, Youssef; Morice, Philippe; Duvillard, Pierre; Gouy, Sébastien; Uzan, Catherine; Gauthier, Hélène; Balleyguier, Corinne; Lhommé, Catherine

    2012-12-01

    Epithelial ovarian cancer frequently presents at an advanced stage where the cornerstone of management remains surgery and platinum-based chemotherapy. Unfortunately, despite sometimes dramatic initial responses, advanced ovarian cancer almost invariably relapses. Little progress has been made in the identification of effective targeted-therapies for ovarian cancer. The majority of clinical trials investigating novel agents have been negative and the only approved targeted-therapy is bevacizumab, for which reliable predictive biomarkers still elude us. Ovarian cancer is treated as a uniform disease. Yet, biological studies have highlighted the heterogeneity of this malignancy with marked differences in histology, oncogenesis, prognosis, chemo-responsiveness, and molecular profile. Recent high throughput molecular analyses have identified a huge number of genomic/phenotypic alterations. Broadly speaking, high grade serous carcinomas (type II) display significant genomic instability and numerous amplifications and losses; low grade (type I) tumors are genomically stable but display frequent mutations. Importantly, many of these genomic alterations relate to known oncogenes for which targeted-therapies are available or in development. There is today a real potential for personalized medicine in ovarian cancer. We will review the current literature regarding the molecular characterization of epithelial ovarian cancer and discuss the biological rationale for a number of targeted strategies. In order to translate these biological advances into meaningful clinical improvements for our patients, it is imperative to incorporate translational research in ovarian cancer trials, a number of strategies will be proposed such as the acquisition of quality tumor samples, including sequential pre- and post-treatment biopsies, the potential of liquid biopsies, and novel trial designs more adapted to the molecular era of ovarian cancer research.

  12. Expression of Multidrug Resistance-Associated Markers, Their Relation to Quantitative Pathologic Tumour Characteristics and Prognosis in Advanced Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Mariël Brinkhuis

    2002-01-01

    Full Text Available Mean nuclear area has been consistently shown by different researchers to be a strong and independent prognostic factor in advanced ovarian carcinoma. However, the biological background of the prognostic value of nuclear area remains unclear. Others have found that the multidrug‐resistance (MDR related protein LRP has strong prognostic value. In the present study we have analysed whether the mean nuclear area and LRP are related in tumour tissue of the ovary obtained at the debulking operation before the administration of chemotherapy in 40 patients. The mitotic activity index, volume percentage epithelium, standard deviation of nuclear area and the other MDR‐related proteins P‐glycoprotein (JSB‐1, MRK‐16 and MRP have been investigated additionally for correlations and prognostic value. No correlations were found between the morphometrical features and MDR‐related proteins. Mean nuclear area tended to be larger in LRP positive tumours, but the correlation was not significant. In multivariate analysis LRP‐protein expression and mean nuclear area had independent prognostic value. Further studies are required to elucidate the biological background of the strong prognostic value of mean nuclear area in advanced ovarian cancer.

  13. The impact of type and number of bowel resections on anastomotic leakage risk in advanced ovarian cancer surgery.

    Science.gov (United States)

    Grimm, Christoph; Harter, Philipp; Alesina, Pier F; Prader, Sonia; Schneider, Stephanie; Ataseven, Beyhan; Meier, Beate; Brunkhorst, Violetta; Hinrichs, Jakob; Kurzeder, Christian; Heitz, Florian; Kahl, Annett; Traut, Alexander; Groeben, Harald T; Walz, Martin; du Bois, Andreas

    2017-09-01

    To identify risk factors for anastomotic leakage (AL) in patients undergoing primary advanced ovarian cancer surgery and to evaluate the prognostic implication of AL on overall survival in these patients. We analyzed our institutional database for primary EOC and included all consecutive patients treated by debulking surgery including any type of full circumferential bowel resection beyond appendectomy between 1999 and 2015. We performed logistic regression models to identify risk factors for AL and log-rank tests and Cox proportional hazards models to evaluate the association between AL and survival. AL occurred in 36/800 (4.5%; 95% confidence interval [3%-6%]) of all patients with advanced ovarian cancer and 36/518 (6.9% [5%-9%]) patients undergoing bowel resection during debulking surgery. One hundred fifty-six (30.1%) patients had multiple bowel resections. In these patients, AL rate per patient was only slightly higher (9.0% [5%-13%]) than in patients with rectosigmoid resection only (6.9% [4%-10%]), despite the higher number of anastomosis. No independent predictive factors for AL were identified. AL was independently associated with shortened overall survival (HR 1.9 [1.2-3.4], p=0.01). In the present study, no predictive pre- and/or intraoperative risk factors for AL were identified. AL rate was mainly influenced by rectosigmoid resection and only marginally increased by additional bowel resections. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Therapeutic advances in multiple system atrophy and progressive supranuclear palsy.

    Science.gov (United States)

    Poewe, Werner; Mahlknecht, Philipp; Krismer, Florian

    2015-09-15

    Multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) are relentlessly progressive neurodegenerative diseases leading to severe disability and ultimately death within less than 10 y. Despite increasing efforts in basic and clinical research, effective therapies for these atypical parkinsonian disorders are lacking. Although earlier small clinical studies in MSA and PSP mainly focused on symptomatic treatment, advances in the understanding of the molecular underpinnings of these diseases and in the search for biomarkers have paved the way for the first large and well-designed clinical trials aiming at disease modification. Targets of intervention in these trials have included α-synuclein inclusion pathology in the case of MSA and tau-related mechanisms in PSP. Since 2013, four large randomized, placebo-controlled, double-blind disease-modification trials have been completed and published, using rasagiline (MSA), rifampicin (MSA), tideglusib (PSP), or davunetide (PSP). All of these failed to demonstrate signal efficacy with regard to the primary outcome measures. In addition, two randomized, placebo-controlled, double-blind trials have studied the efficacy of droxidopa in the symptomatic treatment of neurogenic orthostatic hypotension, including patients with MSA, with positive results in one trial. This review summarizes the design and the outcomes of these and other smaller trials published since 2013 and attempts to highlight priority areas of future therapeutic research in MSA and PSP. © 2015 International Parkinson and Movement Disorder Society. © 2015 International Parkinson and Movement Disorder Society.

  15. Stomatin-like protein 2 is overexpressed in epithelial ovarian cancer and predicts poor patient survival

    International Nuclear Information System (INIS)

    Sun, Fei; Ding, Wen; He, Jie-Hua; Wang, Xiao-Jing; Ma, Ze-Biao; Li, Yan-Fang

    2015-01-01

    factor for survival in epithelial ovarian cancer patients. SLP-2 mRNA and proteins were overexpressed in epithelial ovarian cancer tissues. SLP-2 protein overexpression was associated with advanced stage disease. Patients with higher SLP-2 protein expression had shorter progress free survival and poor overall survival times. Thus, SLP-2 protein expression was an independent prognostic factor for patients with epithelial ovarian cancer

  16. Prognostic significance of mediastinal {sup 18}F-FDG uptake in PET/CT in advanced ovarian cancer

    Energy Technology Data Exchange (ETDEWEB)

    Bats, Anne-Sophie; Lecuru, Fabrice [Universite Paris Descartes, Sorbonne Paris Cite, Faculte de Medecine, Paris (France); Hopital Europeen Georges-Pompidou, Assistance Publique-Hopitaux de Paris, Service de Chirurgie Gynecologique et Cancerologique, Paris (France); Universite Paris Descartes, Sorbonne Paris Cite, INSERM UMR-S 747, Paris (France); Hugonnet, Florent; Faraggi, Marc [Universite Paris Descartes, Sorbonne Paris Cite, Faculte de Medecine, Paris (France); Hopital Europeen Georges-Pompidou, Assistance Publique-Hopitaux de Paris, Service de Medecine Nucleaire, Paris (France); Huchon, Cyrille [Universite Paris Descartes, Sorbonne Paris Cite, Faculte de Medecine, Paris (France); Hopital Europeen Georges-Pompidou, Assistance Publique-Hopitaux de Paris, Service de Chirurgie Gynecologique et Cancerologique, Paris (France); Bensaid, Cherazade [Hopital Europeen Georges-Pompidou, Assistance Publique-Hopitaux de Paris, Service de Chirurgie Gynecologique et Cancerologique, Paris (France); Pierquet-Ghazzar, Nadia [Hopital Europeen Georges-Pompidou, Assistance Publique-Hopitaux de Paris, Service de Medecine Nucleaire, Paris (France)

    2012-03-15

    To evaluate the prognostic significance of increased mediastinal {sup 18}F-FDG uptake in PET/CT for the staging of advanced ovarian cancer. We retrospectively evaluated patients managed for FIGO stage III/IV ovarian cancer between 1 January 2006 and 1 June 2009. Patients were included if they had undergone {sup 18}F-FDG PET/CT and surgery for initial staging. Exclusion criteria were age younger than 18 years, inability to undergo general anaesthesia, recurrent ovarian cancer, and borderline or nonepithelial malignancy. Whole-body PET/CT was performed after intravenous {sup 18}F-FDG injection. The location of abnormal hot spots and {sup 18}F-FDG maximal standard uptake values (SUV{sub max}) were recorded. We compared the complete cytoreduction and survival rates in groups defined based on mediastinal {sup 18}F-FDG uptake and SUV{sub max} values. Kaplan-Meier curves of overall survival and disease-free survival were compared using the log-rank test. Hazard ratios with their 95% confidence intervals were computed. Adjusted hazard ratios were obtained using a multivariate Cox model. We included 53 patients, of whom 17 (32%) had increased mediastinal {sup 18}F-FDG uptake. Complete cytoreduction was achieved in 14 (87.5%) of the 16 patients managed with primary surgery and in 21 (75%) of the 28 patients managed with interval surgery. Complete cytoreduction was achieved significantly more often among patients without increased mediastinal {sup 18}F-FDG uptake (80.6% vs. 35.3%; p = 0.001). Disease-free survival was comparable between the two groups. By univariate analysis, overall mortality was significantly higher among patients with increased mediastinal {sup 18}F-FDG uptake (hazard ratio 5.70, 95% confidence interval 1.74-18.6). The only factor significantly associated with overall survival by multivariate analysis was complete cytoreduction (adjusted hazard ratio 0.24, 95% confidence interval 0.07-0.89). Increased mediastinal {sup 18}F-FDG uptake was common in patients

  17. Lack of relationship between TIMP-1 tumour cell immunoreactivity, treatment efficacy and prognosis in patients with advanced epithelial ovarian cancer

    International Nuclear Information System (INIS)

    Steffensen, Karina Dahl; Waldstrøm, Marianne; Christensen, Rikke Kølby; Bartels, Annette; Brünner, Nils; Jakobsen, Anders

    2010-01-01

    Tissue inhibitor of metalloproteinase 1 (TIMP-1) is a natural inhibitor of the matrix metalloproteinases (MMPs) which are proteolytic enzymes involved in degradation of extracellular matrix thereby favoring tumour cell invasion and metastasis. TIMP-1 activity in tumour tissue may therefore play an essential role in the progression of a malignant tumour. The primary aim of the present study was to evaluate TIMP-1 protein immunoreactivity in tissue from primary ovarian cancer patients and associate these findings with the course of the disease including response to treatment in the individual patient. TIMP-1 was assessed by immunohistochemistry (in tissue micro arrays) in a total of 163 ovarian cancer specimens obtained from primary debulking surgery during 1991-1994 as part of a randomized clinical protocol. Positive TIMP-1 immunoreactivity was found in 12.3% of the tumours. The median survival time for the 143 patients with TIMP-1 negative tumours was 23.7 months [19.0-29.4] 95% CI, while the median survival time for the 20 patients with TIMP-1 positive tumours was 15.9 months [12.3-27.4] 95% CI. Although a difference of 7.8 months in median overall survival in favor of the TIMP-1 tumour negative patients was found, this difference did not reach statistical significance (p = 0.28, Kaplan-Meier, log-rank test). Moreover, TIMP-1 immunoreactivity was not associated with CA125 response (p = 0.53) or response at second look surgery (p = 0.72). TIMP-1 immunoreactivity in tumour tissue from patients with primary epithelial ovarian cancer did not correlate with patient survival or response to combination platinum/cyclophosphamide therapy

  18. Akt2/ZEB2 may be a biomarker for exfoliant cells in ascitic fluid in advanced grades of serous ovarian carcinoma.

    Science.gov (United States)

    Liu, Changmei; Yang, Fangmei

    2015-09-01

    Ovarian cancers present a mild clinical course when diagnosed early but an aggressive pathway when diagnosed in the peri- and postmenopausal periods. However, the predictability of tumor progression is stochastic and is difficult to predict. In the present study, we hypothesized to examine the key pathways that are dysregulated to promote epithelial-mesenchymal transition in serous ovarian carcinoma. Examination of these steps would help to identify ascitic fluid with cells poised for metastasis or otherwise. We focused on examining the Akt2 expression, mainly because of its report as being overamplified in the aggressive variants of ovarian cancer, as well as TGFbeta-sensitivity of Akt2 that forms the key basis for metastasis initiation of most kinds of carcinoma. We obtained primary ovarian carcinoma samples as well as ascitic fluid and distantly metastatic ovarian carcinoma to examine the expression of Akt2. The results of the study demonstrated that in malignant exfoliated ovarian cancer cells, Smad4 expression was tremendously increased in the nuclei, suggesting nuclear translocation of Smad, which thereafter may have activated ZEB2, and thereafter genomically affected the expression of E-cadherin, myosin II, and vimentin, key components for initiating and sustaining metastasis. All of these may have been stimulated by increased cellular expression of Akt2 in metastatic variants of the serous ovarian carcinoma. The reliance on Akt2 and TGF beta signaling may also potentiate the case for Akt inhibitors or small molecule inhibitors of TGFbeta signaling like doxycycline as adjunct chemotherapy in serous ovarian carcinoma, especially the metastatic variants.

  19. Development of A Mouse Model of Menopausal Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Elizabeth R. Smith

    2014-02-01

    Full Text Available Despite significant understanding of the genetic mutations involved in ovarian epithelial cancer and advances in genomic approaches for expression and mutation profiling of tumor tissues, several key questions in ovarian cancer biology remain enigmatic: the mechanism for the well-established impact of reproductive factors on ovarian cancer risk remains obscure; questions of the cell of origin of ovarian cancer continue to be debated; and the precursor lesion, sequence, or events in progression remain to be defined. Suitable mouse models should complement the analysis of human tumor tissues and may provide clues to these questions currently perplexing ovarian cancer biology.A potentially useful model is the germ cell-deficient Wv (white spotting variant mutant mouse line, which may be used to study the impact of menopausal physiology on the increased risk of ovarian cancer. The Wv mice harbor a point mutation in c-Kit that reduces the receptor tyrosine kinase activity to about 1-5% (it is not a null mutation. Homozygous Wv mutant females have a reduced ovarian germ cell reservoir at birth and the follicles are rapidly depleted upon reaching reproductive maturity, but other biological phenotypes are minimal and the mice have a normal life span. The loss of ovarian function precipitates changes in hormonal and metabolic activity that model features of menopause in humans. As a consequence of follicle depletion, the Wv ovaries develop ovarian tubular adenomas, a benign epithelial tumor corresponding to surface epithelial invaginations and papillomatosis that mark human ovarian aging. Ongoing work will test the possibility of converting the benign epithelial tubular adenomas into neoplastic tumors by addition of an oncogenic mutation, such as of Tp53, to model the genotype and biology of serous ovarian cancer.Model based on the Wv mice may have the potential to gain biological and etiological insights into ovarian cancer development and prevention.

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

    Directory of Open Access Journals (Sweden)

    Nexhmi Hyseni

    2014-01-01

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

  1. An advanced case of indium lung disease with progressive emphysema.

    Science.gov (United States)

    Nakano, Makiko; Tanaka, Akiyo; Hirata, Miyuki; Kumazoe, Hiroyuki; Wakamatsu, Kentaro; Kamada, Dan; Omae, Kazuyuki

    2016-09-30

    To report the occurrence of an advanced case of indium lung disease with severely progressive emphysema in an indium-exposed worker. A healthy 42-year-old male smoker was employed to primarily grind indium-tin oxide (ITO) target plates, exposing him to indium for 9 years (1998-2008). In 2004, an epidemiological study was conducted on indium-exposed workers at the factory in which he worked. The subject's serum indium concentration (In-S) was 99.7 μg/l, while his serum Krebs von den Lungen-6 level was 2,350 U/ml. Pulmonary function tests showed forced vital capacity (FVC) of 4.17 l (91.5% of the JRS predicted value), forced expiratory volume in 1 s (FEV 1 ) of 3.19 l (80.8% of predicted), and an FEV 1 -to-FVC ratio of 76.5%. A high-resolution chest computed tomography (HRCT) scan showed mild interlobular septal thickening and mild emphysematous changes. In 2008, he was transferred from the ITO grinding workplace to an inspection work section, where indium concentrations in total dusts had a range of 0.001-0.002 mg/m 3 . In 2009, the subject's In-S had increased to 132.1 μg/l, and pulmonary function tests revealed obstructive changes. In addition, HRCT scan showed clear evidence of progressive lung destruction with accompanying severe centrilobular emphysema and interlobular septal thickening in both lung fields. The subject's condition gradually worsened, and in 2015, he was registered with the Japan Organ Transplant Network for lung transplantation (LTx). Heavy indium exposure is a risk factor for emphysema, which can lead to a severity level that requires LTx as the final therapeutic option.

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

    Directory of Open Access Journals (Sweden)

    Mitsuko Furuya

    2012-07-01

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

  3. Inflammation-regulating factors in ascites as predictive biomarkers of drug resistance and progression-free survival in serous epithelial ovarian cancers

    International Nuclear Information System (INIS)

    Lane, Denis; Matte, Isabelle; Garde-Granger, Perrine; Laplante, Claude; Carignan, Alex; Rancourt, Claudine; Piché, Alain

    2015-01-01

    Platinum-based combination therapy is the standard first-line treatment for women with advanced serous epithelial ovarian carcinoma (EOC). However, about 20 % will not respond and are considered clinically resistant. The availability of biomarkers to predict responses to the initial therapy would provide a practical approach to identify women who would benefit from a more appropriate first-line treatment. Ascites is an attractive inflammatory fluid for biomarker discovery as it is easy and minimally invasive to obtain. The aim of this study was to evaluate whether six selected inflammation-regulating factors in ascites could serve as diagnostic or drug resistance biomarkers in patients with advanced serous EOC. A total of 53 women with stage III/IV serous EOC and 10 women with benign conditions were enrolled in this study. Eleven of the 53 women with serous EOC were considered clinically resistant to treatment with progression-free survival < 6 months. Ascites were collected at the time of the debulking surgery and the levels of cytokines were measured by ELISA. The six selected cytokines were evaluated for their ability to discriminate serous EOC from benign controls, and to discriminate platinum resistant from platinum sensitive patients. Median ascites levels of IL-6, IL-10 and osteoprotegerin (OPG) were significantly higher in women with advanced serous EOC than in controls (P ≤ 0.012). There were no significant difference in the median ascites levels of leptin, soluble urokinase plasminogen activator receptor (suPAR) and CCL18 among serous EOC women and controls. In Receiver Operator curve (ROC) analysis, IL-6, IL-10 and OPG had a high area under the curve value of 0.905, 0.832 and 0.825 respectively for distinguishing EOC from benign controls. ROC analysis of individual cytokines revealed low discriminating potential to stratify patients according to their sensitivity to first-line treatment. The combination of biomarkers with the highest discriminating

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    Abstract Introduction. In patients with advanced ovarian cancer undergoing preoperative PET/CT, we investigated the prognostic value of SUV in the primary tumor and we evaluated the value of SUV for predicting incomplete primary cytoreduction (macroscopic residual tumor). Material and methods. From...... debulking (no macroscopic residual tumor); median SUV(max) was 13.5 (range 2.5-39.0). Median follow-up was 30.2 months. At follow-up 57% (34/60) were alive and 43% (26/60) had died from ovarian cancer. SUV(max) in patients alive was not statistically different from SUV(max) in dead patients (p=0.......69), and SUV(max) was not correlated with the amount of residual tumor after surgery (p=0.19). Using univariate Cox regression analysis, residual tumor was a significant prognostic variable (p=0.001); SUV(max) was not a statistically significant prognostic variable (p=0.86). Discussion. FDG uptake (SUV...

  5. Effect of DC-CIK treatment on tumor markers and T cell subsets in patients with advanced ovarian cancer

    Directory of Open Access Journals (Sweden)

    Jie-Qun Guo

    2016-10-01

    Full Text Available Objective: To investigate the effects of dendritic cells (DC and cytokine induced killer cells (CIK on tumor markers and T cell subsets in peripheral blood of patients with advanced ovarian cancer. Methods: A total of 100 cases of patients with advanced ovarian cancer who were proved by operation and pathology in the department of gynecologic oncology in our hospital were selected from April 2013 to April 20l6, and randomly divided into experimental group and control group, the control group was treated with TC (Taxinol+Cisplat chemotherapy alone, the experimental group was treated with DC-CIK combined with chemotherapy. Before and after treatment, the changes of CD3+, CD4+, CD8+, CD4+/CD8+, CD4+/CD25+, NK cells in peripheral blood and serum tumor markers (CA125, CA19-9, HE4 were detected. Results: Before treatment, the phenotypes of T cell subsets in the two groups were not significantly different; in the experimental group after treatment, the levels of CD3+, CD4+, CD4+/CD8+, and NK cells were increased,while the levels of CD4+/CD25+ and CD8+ were decreased, compared with before treatment, the differences were statistically significant; the phenotype changes of T cells were not statistically significant before and after treatment in the control group; after treatment, there were significant differences in the levels of CD4+, CD8+, CD4+/CD8+, CD4+/CD25+ and NK cells between the two groups. Before treatment, there were no significant differences in HE4 value, CA125 value and CA19-9 value between the two groups; after treatment, the tumor markers in the two groups were all decreased, and the difference was significant as compared with those before treatment; after treatment, the CA125 value, CA19-9 value and HE4 value were (73.68±79.46 U/mL, (54.32±32.85 U/mL and (69.57±39.85 pmol/L respectively, the values of three tumor markers were compared with the control group, with a statistical difference. Conclusion: DC-CIK treatment can improve the

  6. Rucaparib: a novel PARP inhibitor for BRCA advanced ovarian cancer

    Directory of Open Access Journals (Sweden)

    Colombo I

    2018-03-01

    Full Text Available Ilaria Colombo, Stephanie Lheureux, Amit Manulal Oza Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada Abstract: Rucaparib is a potent small-molecule inhibitor of poly (ADP-ribose polymerase (PARP proteins (PARP-1, PARP-2 and PARP-3 that play an important role in repairing DNA damage and maintaining genomic stability. Tumors with mutations in BRCA1/2 or other homologous recombination deficiency (HRD genes are particularly sensitive to PARP inhibitors because of “synthetic lethality”, whereby a therapeutic agent can take advantage of an intrinsic weakness in DNA repair. Rucaparib has been investigated in several preclinical and clinical studies showing promising activity in BRCA-mutant and BRCA–wild-type epithelial ovarian cancers (EOCs. Dose-escalation Phase I studies have established the recommended Phase II dose to be 600 mg twice a day for oral rucaparib. Phase II and III studies have defined its role as treatment for BRCA-mutant recurrent high-grade EOC and as maintenance treatment for platinum-sensitive relapsed EOC following response to platinum-based chemotherapy. Genomic loss of heterozygosity has also been investigated as a potential signature of HRD and as a potential predictive biomarker of response. Treatment-induced adverse events (AEs have been observed in almost all patients treated with rucaparib, but mainly lower grade; with the most common being nausea, vomiting, asthenia/fatigue, anemia and transient transaminitis. The majority of AEs occurred early in treatment, were transient and have been easily managed with supportive treatment, dose interruption or discontinuation. This review will analyze the results of clinical trials investigating efficacy and safety of rucaparib in patients with ovarian cancer. Keywords: rucaparib, ovarian cancer, BRCA mutations, homologous recombination deficiency, maintenance treatment, PARP inhibitor

  7. Combination of radiotherapy and selective chemotherapy in the treatment of advanced ovarian carcinomas

    International Nuclear Information System (INIS)

    Dietz, R.; Brachetti, A.; Universitaet des Saarlandes, Homburg/Saar

    1982-01-01

    A report is given on 160 patients suffering from ovarian carcinomas the stages which were exactly determined by TNM classification. 32 patients had tumors of the stages T1-T3, 128 patients had tumors of the stage T4. All T3 subgroups showed favorable results after radical surgery and a postoperative combination of radiotherapy and selective cytostatic chemotherapy. The therapy plans including radiotherapy had more advantages than those without radiotherapy. Furthermore, the cytostatic treatment was more successful after a chemotherapy resistance test than after blind administration of cytostatic drugs. (orig.) [de

  8. Progress in development of the advanced Thomson scattering diagnostics

    International Nuclear Information System (INIS)

    Hatae, T; Naito, O; Howard, J; Ebizuka, N; Yoshida, H; Nakatsuka, M; Fujita, H; Kajita, S; Narihara, K; Yamada, I; Funaba, H; Hirano, Y; Koguchi, H

    2010-01-01

    We have been studied the advanced Thomson scattering diagnostics from viewpoints of new concepts, laser technology and spectrum analysis. This paper summarizes results of development on technologies for advanced Thomson scattering diagnostics.

  9. First-line treatment of advanced ovarian cancer with paclitaxel/carboplatin with or without epirubicin (TEC versus TC)-a gynecologic cancer intergroup study of the NSGO, EORTC GCG and NCIC CTG

    DEFF Research Database (Denmark)

    Lindemann, K.; Christensen, R. D.; Vergote, I.

    2012-01-01

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

  10. Prognostic significance of the number of postoperative intraperitoneal chemotherapy cycles for patients with advanced epithelial ovarian cancer.

    Science.gov (United States)

    Suidan, Rudy S; Zhou, Qin; Iasonos, Alexia; O'Cearbhaill, Roisin E; Chi, Dennis S; Long Roche, Kara C; Tanner, Edward J; Denesopolis, John; Barakat, Richard R; Zivanovic, Oliver

    2015-05-01

    Phase 3 trials have demonstrated a survival advantage for patients with optimally debulked epithelial ovarian cancer who received intravenous (IV) and intraperitoneal (IP) chemotherapy compared with IV therapy alone. This was despite a significant proportion of patients in the IV/IP arms not completing all 6 planned cycles. Our objective was to evaluate the prognostic significance of the number of IV/IP cycles administered. Data were analyzed for all patients with stage III to IV epithelial ovarian cancer who underwent optimal primary cytoreduction followed by 1 or more cycles of IV/IP chemotherapy from January 2005 to July 2011 at our institution. A landmark analysis was performed to associate progression-free survival (PFS) and overall survival (OS) with the number of IV/IP cycles given. We identified 201 patients; 26 (13%) received 1 to 2 cycles of IV/IP chemotherapy, 41 (20%) received 3 to 4 cycles, and 134 (67%) received 5 to 6 cycles. The 5-year PFS for patients who received 1 to 2, 3 to 4, and 5 to 6 cycles was 18%, 29%, and 17%, respectively. The 5-year OS for patients who received 1 to 2, 3 to 4, and 5 to 6 cycles was 44%, 54%, and 57%, respectively. There was no significant difference in PFS (P = 0.31) or OS (P = 0.14) between the 3 groups. The most common reason for discontinuing IV/IP therapy was treatment-related toxicity (77%). Postoperative complications were the most common reason for not initiating IV/IP therapy (42%) in patients who subsequently transitioned to it. We did not detect a significant survival difference between patients who received 1 to 2, 3 to 4, or 5 to 6 IV/IP chemotherapy cycles. Women may still derive a survival benefit if they receive fewer than 6 IV/IP cycles.

  11. Whole abdomen radiation therapy after a short chemotherapy course and second-look laparotomy in advanced ovarian cancer

    International Nuclear Information System (INIS)

    Franchin, G.; Tumolo, S.; Scarabelli, C.; De Paoli, A.; Boz, G.; Crivellari, D.; Arcicasa, M.; Bortolus, R.; Gobitti, C.; Minatel, E.

    1991-01-01

    From April 1983 through December 1989, 42 consecutive patients with diagnosis of epithelial ovarian carcinoma were initially managed by aggressive surgery and three courses of endoperitoneal cis-platinum-based chemotherapy followed by an alternating combination chemotherapy and second-look laparotomy. Patients with residual tumor less than or equal to 2 cm subsequently received whole abdominal radiation therapy (WAR). Twenty-eight patients (42% with no residual disease, 21% with microscopic disease, and 36% with residual disease less than 2 cm) were eligible for WAR. WAR was delivered using an open-field technique up to 22 Gy in 20 fractions followed by a pelvic boost of 18 Gy in 10 fractions. The kidneys were shielded posteriorly at 1100 cGy; hepatic shields were not added. One patient did not complete WAR for lung metastases after 5 radiotherapy fractions. The complete treatment program lasted 8 months (range, 6.8-11). The median follow-up of the 28 patients entered into the study was 50 months. Eight patients are alive and disease-free at 5 years. The overall and disease-free survival rates at 5 years are 45 and 30%, respectively. All but 2 patients relapsed within the abdominopelvic cavity and 3 developed brain metastases. Toxic effects, during WAR, required treatment interruption in all but 4 patients: 3 developed a small bowel obstruction requiring surgery and 1 died of surgical complications in complete remission. The poor disease-free survival and the severe toxicity encountered have been valid indications that WAR should be discontinued as a treatment modality in advanced ovarian cancer at the authors department

  12. Body weight, hemoglobin, and absolute neutrophil count in patients with advanced-stage epithelial ovarian cancer who received chemotherapy: A single-center study

    Science.gov (United States)

    Gunawan, Y.; Winarto, H.

    2017-08-01

    The side effects of chemotherapy, a treatment modality of ovarian cancer, can disrupt overall treatment. To date, the clinical and laboratory profiles of ovarian cancer patients during chemotherapy have not been investigated. This study aimed to elucidate the clinical and laboratory profiles of patients with advanced-stage epithelial ovarian cancer who received chemotherapy in Dr. Cipto Mangunkusumo Hospital, including body mass index (BMI), hemoglobin (Hb), and absolute neutrophil count (ANC). To generate these clinical and laboratory profiles, we collected secondary data from the medical records of advanced-stage epithelial ovarian cancer patients who received six cycles of carboplatin and paclitaxel chemotherapy. We enrolled 23 patients with advanced-stage epithelial ovarian cancer patients who received six cycles of chemotherapy. Mean patient BMI before and after chemotherapy was 22.86 kg/m2 and 21.78 kg/m2, respectively. Hb levels before chemotherapy were 8-13 g/dl, with Hb chemotherapy. Mean ANC before chemotherapy was 3.5582 ± 3.3250. An average of 26.81% of patients had ANC chemotherapy; no patients had ANC chemotherapy initiation. After six cycles of chemotherapy, three patients (13.04%) had mild neutropenia, four patients (17.39%) had moderate neutropenia, and one patient (4.35%) had severe neutropenia. Of the 22 patients with Hb ≥ 10 g/dl before chemotherapy, 16 (72.72%) experienced a decrease in ANC during chemotherapy. Of the 20 patients (60.87%) with normal BMI or higher, 14 experienced a decrease in ANC during chemotherapy. The mean patient body weight decreased after six cycles of chemotherapy. Hb and ANC were persistently decreased in approximately a quarter of the 23 subjects. The decrease in ANC was not influenced by initial Hb and BMI.

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

    Directory of Open Access Journals (Sweden)

    Sheikh Zahoor Ahmad

    2015-01-01

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

  14. FY2014 Advanced Combustion Engine Annual Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    None

    2015-03-01

    The Advanced Combustion Engine research and development (R&D) subprogram within the DOE Vehicle Technologies Office (VTO) provides support and guidance for many cutting-edge automotive technologies under development. Research focuses on addressing critical barriers to commercializing higher efficiency, very low emissions advanced internal combustion engines for passenger and commercial vehicles.

  15. FY2016 Advanced Combustion Engine Annual Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    None, None

    2017-07-01

    The Advanced Combustion Engine research and development (R&D) subprogram within the DOE Vehicle Technologies Office (VTO) provides support and guidance for many cutting-edge automotive technologies under development. Research focuses on addressing critical barriers to commercializing higher efficiency, very low emissions advanced internal combustion engines for passenger and commercial vehicles.

  16. FY2015 Advanced Combustion Engine Annual Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Gurpreet [Vehicle Technologies Office, Washington, DC (United States); Gravel, Roland M. [Vehicle Technologies Office, Washington, DC (United States); Howden, Kenneth C. [Vehicle Technologies Office, Washington, DC (United States); Breton, Leo [Vehicle Technologies Office, Washington, DC (United States)

    2016-03-25

    The Advanced Combustion Engine research and development (R&D) subprogram within the DOE Vehicle Technologies Office (VTO) provides support and guidance for many cutting-edge automotive technologies under development. Research focuses on addressing critical barriers to commercializing higher efficiency, very low emissions advanced internal combustion engines for passenger and commercial vehicles.

  17. Interleukin 6 Present in Inflammatory Ascites from Advanced Epithelial Ovarian Cancer Patients Promotes Tumor Necrosis Factor Receptor 2-Expressing Regulatory T Cells

    Directory of Open Access Journals (Sweden)

    Nirmala Chandralega Kampan

    2017-11-01

    Full Text Available BackgroundEpithelial ovarian cancer (EOC remains a highly lethal gynecological malignancy. Ascites, an accumulation of peritoneal fluid present in one-third of patients at presentation, is linked to poor prognosis. High levels of regulatory T cells (Tregs in ascites are correlated with tumor progression and reduced survival. Malignant ascites harbors high levels of Tregs expressing the tumor necrosis factor receptor 2 (TNFR2, as well as pro-inflammatory factors such as interleukin 6 (IL-6 and tumor necrosis factor (TNF. IL-6 is also associated with poor prognosis. Herein, we study the effect of IL-6 and TNF present in ascites on the modulation of TNFR2 expression on T cells, and specifically Tregs.MethodsAscites and respective peripheral blood sera were collected from 18 patients with advanced EOC and soluble biomarkers, including IL-6, sTNFR2, IL-10, TGF-β, and TNF, were quantified using multiplexed bead-based immunoassay. Peripheral blood mononuclear cells (PBMC from healthy donors were incubated with cell-free ascites for 48 h (or media as a negative control. In some experiments, IL-6 or TNF within the ascites were neutralized by using monoclonal antibodies. The phenotype of TNFR2+ Tregs and TNFR2− Tregs were characterized post incubation in ascites. In some experiments, cell sorted Tregs were utilized instead of PBMC.ResultsHigh levels of immunosuppressive (sTNFR2, IL-10, and TGF-β and pro-inflammatory cytokines (IL-6 and TNF were present in malignant ascites. TNFR2 expression on all T cell subsets was higher in post culture in ascites and highest on CD4+CD25hiFoxP3+ Tregs, resulting in an increased TNFR2+ Treg/effector T cell ratio. Furthermore, TNFR2+ Tregs conditioned in ascites expressed higher levels of the functional immunosuppressive molecules programmed cell death ligand-1, CTLA-4, and GARP. Functionally, TNFR2+ Treg frequency was inversely correlated with interferon-gamma (IFN-γ production by effector T cells, and was

  18. Germline polymorphisms in an enhancer of PSIP1 are associated with progression-free survival in epithelial ovarian cancer

    DEFF Research Database (Denmark)

    French, Juliet D; Johnatty, Sharon E; Lu, Yi

    2016-01-01

    Women with epithelial ovarian cancer (EOC) are usually treated with platinum/taxane therapy after cytoreductive surgery but there is considerable inter-individual variation in response. To identify germline single-nucleotide polymorphisms (SNPs) that contribute to variations in individual responses...... binding of the Sp1 transcription factor, which is critical for chromatin interactions with PSIP1. Silencing of PSIP1 significantly impaired DNA damage-induced Rad51 nuclear foci and reduced cell viability in ovarian cancer lines. PSIP1 (PC4 and SFRS1 Interacting Protein 1) is known to protect cells from...

  19. Preferential Allele Expression Analysis Identifies Shared Germline and Somatic Driver Genes in Advanced Ovarian Cancer

    Science.gov (United States)

    Halabi, Najeeb M.; Martinez, Alejandra; Al-Farsi, Halema; Mery, Eliane; Puydenus, Laurence; Pujol, Pascal; Khalak, Hanif G.; McLurcan, Cameron; Ferron, Gwenael; Querleu, Denis; Al-Azwani, Iman; Al-Dous, Eman; Mohamoud, Yasmin A.; Malek, Joel A.; Rafii, Arash

    2016-01-01

    Identifying genes where a variant allele is preferentially expressed in tumors could lead to a better understanding of cancer biology and optimization of targeted therapy. However, tumor sample heterogeneity complicates standard approaches for detecting preferential allele expression. We therefore developed a novel approach combining genome and transcriptome sequencing data from the same sample that corrects for sample heterogeneity and identifies significant preferentially expressed alleles. We applied this analysis to epithelial ovarian cancer samples consisting of matched primary ovary and peritoneum and lymph node metastasis. We find that preferentially expressed variant alleles include germline and somatic variants, are shared at a relatively high frequency between patients, and are in gene networks known to be involved in cancer processes. Analysis at a patient level identifies patient-specific preferentially expressed alleles in genes that are targets for known drugs. Analysis at a site level identifies patterns of site specific preferential allele expression with similar pathways being impacted in the primary and metastasis sites. We conclude that genes with preferentially expressed variant alleles can act as cancer drivers and that targeting those genes could lead to new therapeutic strategies. PMID:26735499

  20. Progress in diagnosis of breast cancer: Advances in radiology technology

    Directory of Open Access Journals (Sweden)

    J Mari Beth Linder

    2015-01-01

    Full Text Available Breast cancer is the leading cause of cancer in females between the ages of 15 and 54, and the second leading cause of cancer death in women in the United States. Diagnosis begins with detection by breast examination (clinical breast exam or breast self-exam or by radiologic studies, like mammography. Many advances in the diagnosis of breast cancer have taken place in recent years. This article will review the history of radiologic advances in the diagnosis of breast cancer. Use of technological advancements in digital breast tomosynthesis, magnetic resonance imaging, and ultrasound in breast cancer diagnosis will be presented. Advantages and disadvantages of these diagnostic interventions when compared to older, traditional X-ray films will be discussed. It is important for all nurses, including radiology and oncology nurses, to be well informed about these varied diagnostic modalities, and appreciate the fact that advances in radiologic imaging technologies can yield improved outcomes for breast cancer patients.

  1. FY 2007 Progress Report for Advanced Combustion Engine Technologies

    Energy Technology Data Exchange (ETDEWEB)

    None, None

    2007-12-01

    Advanced combustion engines have great potential for achieving dramatic energy efficiency improvements in light-duty vehicle applications, where it is suited to both conventional and hybrid- electric powertrain configurations. Light-duty vehicles with advanced combustion engines can compete directly with gasoline engine hybrid vehicles in terms of fuel economy and consumer-friendly driving characteristics; also, they are projected to have energy efficiencies that are competitive with hydrogen fuel cell vehicles when used in hybrid applications.Advanced engine technologies being researched and developed by the Advanced Combustion Engine R&D Sub-Program will also allow the use of hydrogen as a fuel in ICEs and will provide an energy-efficient interim hydrogen-based powertrain technology during the transition to hydrogen/fuelcell-powered transportation vehicles.

  2. Over-expression of Eph and ephrin genes in advanced ovarian cancer: ephrin gene expression correlates with shortened survival

    Directory of Open Access Journals (Sweden)

    Lincoln Douglas

    2006-06-01

    Full Text Available Abstract Background Increased expression of Eph receptor tyrosine kinases and their ephrin ligands has been implicated in tumor progression in a number of malignancies. This report describes aberrant expression of these genes in ovarian cancer, the commonest cause of death amongst gynaecological malignancies. Methods Eph and ephrin expression was determined using quantitative real time RT-PCR. Correlation of gene expression was measured using Spearman's rho statistic. Survival was analysed using log-rank analysis and (was visualised by Kaplan-Meier survival curves. Results Greater than 10 fold over-expression of EphA1 and a more modest over-expression of EphA2 were observed in partially overlapping subsets of tumors. Over-expression of EphA1 strongly correlated (r = 0.801; p Conclusion These data imply that increased levels of ephrins A1 and A5 in the presence of high expression of Ephs A1 and A2 lead to a more aggressive tumor phenotype. The known functions of Eph/ephrin signalling in cell de-adhesion and movement may explain the observed correlation of ephrin expression with poor prognosis.

  3. Effect of continuous recombinant human endostatin pumping combined with TP chemotherapy on serum malignant molecules and angiogenesis molecules in patients with advanced ovarian cancer

    Directory of Open Access Journals (Sweden)

    Wei-Dong Chen

    2017-05-01

    Full Text Available Objective: To study the effect of continuous recombinant human endostatin pumping combined with TP chemotherapy on serum malignant molecules and angiogenesis molecules in patients with advanced ovarian cancer. Methods: 78 patients with advanced ovarian cancer who were treated in our hospital between July 2011 and December 2015 were selected and divided into observation group and control group (n=39 according to the single-blind randomized control method. Before treatment and after 4 cycles of treatment, electrochemical luminescence immunity analyzer was used to detect serum tumor marker levels; RIA method was used to determine serum apoptosis molecule levels; enzyme-linked immunosorbent assay (ELISA was used to detect the serum angiogenesis molecule levels. Results: Before treatment, differences in serum levels of tumor markers, apoptosis molecules and angiogenesis molecules were not statistically significant between two groups of patients (P>0.05. After 4 cycles of treatment, serum carbohydrate antigen 125 (CA125, carbohydrate antigen 153 (CA153, human epididymis protein 4 (HE4, carcinoembryonic antigen (CEA, human chorionic gonadotropin (β-HCG, Bcl-2, Survivin, Bag-1, angiogenin-2 (Ang-2, vascular endothelial growth factor (VEGF and basic fibroblast growth factor (bFGF levels of observation group were significantly lower than those of control group (P<0.05 while Bax level was significantly higher than that of control group (P<0.05. Conclusions: Continuous recombinant human endostatin pumping combined with TP chemotherapy can decrease the malignant degree of advanced ovarian cancer and inhibit angiogenesis.

  4. A case report of long term bevacizumab treatment in multiresistant ovarian cancer

    DEFF Research Database (Denmark)

    Kargo, Anette Stolberg; Adimi, Parvin; Dahl-Steffensen, Karina

    2016-01-01

    Treatment of multiresistant ovarian cancer is palliative and patients have needs for less toxic treatment. Anti-angiogenic treatments have a less toxic profile, and bevacizumab has shown improvement of progression free survival (PFS) in front-line trials. Bevacizumab is generally introduced in co...... in combination with chemotherapy; however this case report will describe the use of single-agent bevacizumab for more than five years (102 cycles) in a patient with relapse of advanced ovarian cancer...

  5. Complete cytoreduction after five or more cycles of neo-adjuvant chemotherapy confers a survival benefit in advanced ovarian cancer.

    Science.gov (United States)

    Phillips, Andrew; Sundar, Sudha; Singh, Kavita; Nevin, James; Elattar, Ahmed; Kehoe, Sean; Balega, Janos

    2018-06-01

    To assess the impact of 5 or more cycles of neoadjuvant chemotherapy (NACT) and cytoreductive outcomes on overall survival (OS) in patients undergoing interval debulking surgery (IDS) for advanced ovarian cancer. A retrospective review of patients receiving NACT followed by IDS between 2007 and 2017. Patients were analysed according to number of NACT cycles received: group 1 consisted of patients receiving ≤4 cycles and group 2 consisted of those receiving ≥5 cycles. Outcomes were stratified by cytoreductive outcome, surgical complexity, stage and chemotherapy exposure. 231 patients in group 1 and 167 in group 2 were identified. In group 1, the OS for those achieving Complete (R0), Optimalcycles to 24.3 (95%CI 14.4-34.2)months with ≥6 cycles. Surgery with utilisation of cytoreductive procedures to achieve complete clearance should be offered to all patients even after ≥5 cycles if R0 can be achieved. R1 cytoreduction has questionable value in those receiving ≤4 cycles and no value in those receiving ≥5 cycles. Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

  6. FY2009 Annual Progress Report for Advanced Power Electronics

    Energy Technology Data Exchange (ETDEWEB)

    Rogers, Susan A. [Dept. of Energy (DOE), Washington DC (United States)

    2010-01-01

    The Advanced Power Electronics and Electric Machines (APEEM) subprogram within the Vehicle Technologies Program provides support and guidance for many cutting-edge automotive technologies now under development. Research is focused on understanding and improving the way the various new components of tomorrow's automobiles will function as a unified system to improve fuel efficiency.

  7. Advanced Industrial Materials (AIM) Program: Annual progress report FY 1995

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-04-01

    In many ways, the Advanced Industrial Materials (AIM) Program underwent a major transformation in Fiscal Year 1995 and these changes have continued to the present. When the Program was established in 1990 as the Advanced Industrial Concepts (AIC) Materials Program, the mission was to conduct applied research and development to bring materials and processing technologies from the knowledge derived from basic research to the maturity required for the end use sectors for commercialization. In 1995, the Office of Industrial Technologies (OIT) made radical changes in structure and procedures. All technology development was directed toward the seven ``Vision Industries`` that use about 80% of industrial energy and generated about 90% of industrial wastes. The mission of AIM has, therefore, changed to ``Support development and commercialization of new or improved materials to improve productivity, product quality, and energy efficiency in the major process industries.`` Though AIM remains essentially a National Laboratory Program, it is essential that each project have industrial partners, including suppliers to, and customers of, the seven industries. Now, well into FY 1996, the transition is nearly complete and the AIM Program remains reasonably healthy and productive, thanks to the superb investigators and Laboratory Program Managers. This Annual Report for FY 1995 contains the technical details of some very remarkable work by the best materials scientists and engineers in the world. Areas covered here are: advanced metals and composites; advanced ceramics and composites; polymers and biobased materials; and new materials and processes.

  8. Advancing functional dysconnectivity and atrophy in progressive supranuclear palsy

    Directory of Open Access Journals (Sweden)

    Jesse A. Brown

    2017-01-01

    Full Text Available Progressive supranuclear palsy syndrome (PSP-S results from neurodegeneration within a network of brainstem, subcortical, frontal and parietal cortical brain regions. It is unclear how network dysfunction progresses and relates to longitudinal atrophy and clinical decline. In this study, we evaluated patients with PSP-S (n = 12 and healthy control subjects (n = 20 at baseline and 6 months later. Subjects underwent structural MRI and task-free functional MRI (tf-fMRI scans and clinical evaluations at both time points. At baseline, voxel based morphometry (VBM revealed that patients with mild-to-moderate clinical symptoms showed structural atrophy in subcortex and brainstem, prefrontal cortex (PFC; supplementary motor area, paracingulate, dorsal and ventral medial PFC, and parietal cortex (precuneus. Tf-fMRI functional connectivity (FC was examined in a rostral midbrain tegmentum (rMT-anchored intrinsic connectivity network that is compromised in PSP-S. In healthy controls, this network contained a medial parietal module, a prefrontal-paralimbic module, and a subcortical-brainstem module. Baseline FC deficits in PSP-S were most severe in rMT network integrative hubs in the prefrontal-paralimbic and subcortical-brainstem modules. Longitudinally, patients with PSP-S had declining intermodular FC between the subcortical-brainstem and parietal modules, while progressive atrophy was observed in subcortical-brainstem regions (midbrain, pallidum and posterior frontal (perirolandic cortex. This suggested that later-stage subcortical-posterior cortical change may follow an earlier-stage subcortical-anterior cortical disease process. Clinically, patients with more severe baseline impairment showed greater subsequent prefrontal-parietal cortical FC declines and posterior frontal atrophy rates, while patients with more rapid longitudinal clinical decline showed coupled prefrontal-paralimbic FC decline. VBM and FC can augment disease monitoring in PSP

  9. Prognosis for advanced-stage primary peritoneal serous papillary carcinoma and serous ovarian cancer in Taiwan

    Directory of Open Access Journals (Sweden)

    Kuan-Chong Chao

    2013-03-01

    Conclusion: PFS was similar for advanced-stage PSPC and PSOC patients. Since the PSPC patients tended to be older and have more high-grade tumors, OS was shorter for PSPC than for POSC patients. Thus, management of the two types of cancer should not differ.

  10. Surgical Techniques for Diaphragmatic Resection During Cytoreduction in Advanced or Recurrent Ovarian Carcinoma: A Systematic Review and Meta-analysis.

    Science.gov (United States)

    Bogani, Giorgio; Ditto, Antonino; Martinelli, Fabio; Lorusso, Domenica; Chiappa, Valentina; Donfrancesco, Cristina; Di Donato, Violante; Indini, Alice; Aletti, Giovanni; Raspagliesi, Francesco

    2016-02-01

    Optimal cytoreduction is one the main factors improving survival outcomes in patients affected by ovarian cancer (OC). It is estimated that approximately 40% of OC patients have gross disease located on the diaphragm. However, no mature data evaluating outcomes of surgical techniques for the management of diaphragmatic carcinosis exist. In the present study, we aimed to estimate surgery-related morbidity of different surgical techniques for diaphragmatic cytoreduction in advanced or recurrent OC. PubMed (MEDLINE), Web of Science, and Clincaltrials.gov databases were searched for records estimating outcomes of diaphragmatic peritoneal stripping (DPS) or diaphragmatic full-thickness resection (DFTR) for OC. The meta-analysis was performed using the Cochrane Review software. For the final analysis, 5 articles were available, including 272 patients. Diaphragmatic peritoneal stripping and DFTR were performed in 197 patients (72%) and 75 patients (28%), respectively. Pooled analysis suggested that the estimated pleural effusion rate was 43% and 51% after DPS and DFTR, respectively. The need for pleural punctures or chest tube placement was 4% and 9% after DPS and DFTR, respectively. The rate of postoperative pneumothorax (4% vs 9%; odds ratio, 0.31; 95% confidence interval, 0.05-2.08) and subdiaphragmatic abscess (3% vs 3%; odds ratio, 0.45; 95% confidence interval, 0.09-2.31) were similar after the execution of DPS and DFTR. Diaphragmatic surgery is a crucial step during cytoreduction for advanced or recurrent OC. Obviously, the choice to perform DPS or DFTR depends on the infiltration of the diaphragmatic muscle or not. Both the procedures are associated with a low pulmonary complication and chest tube placement rates.

  11. Histologic parameters predictive of disease outcome in women with advanced stage ovarian carcinoma treated with neoadjuvant chemotherapy.

    Science.gov (United States)

    Samrao, Damanzoopinder; Wang, Dan; Ough, Faith; Lin, Yvonne G; Liu, Song; Menesses, Teodulo; Yessaian, Annie; Turner, Nicole; Pejovic, Tanja; Mhawech-Fauceglia, Paulette

    2012-12-01

    The use of neoadjuvant chemotherapy followed by tumor reduction surgery, also called interval debulking surgery (IDS), is considered an alternative therapeutic regimen for selected patients with advanced stage epithelial ovarian cancer (EOC). Although minimal residual disease has been proven to be a prognostic factor in traditional cytoreduction for advanced stage EOC, predictive factors after IDS still remain unexplored. The aim of this study was to determine the prognostic value of post-neoadjuvant histologic changes with clinical outcome. Three pathologists evaluated 67 cases for the following parameters: fibrosis, necrosis, residual tumor, and inflammation. The Cohen's kappa statistic was used to measure agreement among pathologists. Univariate and multivariate Cox proportional hazards models were used to determine the association between histologic parameters and recurrence-free survival (RFS) and overall survival (OS). There was substantial to almost perfect agreement among the three pathologists in all four histologic parameters (k ranged from 0.65 to 0.97). Fibrosis was associated with longer RFS (P = 0.0257) with a median of 20 months for tumors with fibrosis (3+) versus 12 months for tumors with fibrosis (1+, 2+) and longer OS (P = 0.0249) with a median of 51 months for tumors with fibrosis (3+) versus 32 months for tumors with fibrosis (1+, 2+). Our results revealed that patients with tumors exhibiting fibrosis (1+, 2+), as well as necrosis (0, 1+), had significant shorter RFS and OS (P = 0.059 and P = 0.0234, respectively). We suggest that the assessment of fibrosis and necrosis should be implemented in pathologic evaluation and prospectively validated in future studies.

  12. Advanced Neutron Source (ANS) Project Progress report, FY 1991

    International Nuclear Information System (INIS)

    Campbell, J.H.; Selby, D.L.; Harrington, R.M.; Thompson, P.B.

    1992-01-01

    This report discusses the following about the Advanced Neutron Source: Project Management; Research and Development; Fuel Development; Corrosion Loop Tests and Analyses; Thermal-Hydraulic Loop Tests; Reactor Control and Shutdown Concepts; Critical and Subcritical Experiments; Material Data, Structural Tests, and Analysis; Cold-Source Development; Beam Tube, Guide, and Instrument Development; Hot-Source Development; Neutron Transport and Shielding; I ampersand C Research and Development; Design; and Safety

  13. Developing Inhibitors of Ovarian Cancer Progression by Targeted Disruption of the Gamma-Synuclein Activated Migratory and Survival Signaling Pathways

    Science.gov (United States)

    2007-04-01

    Golub TR. A molecular signature of metastasis in primary solid tumors. Nat Gene 2003;33:49–54. 2. van’t Verr LJ, Dai H, van de Vijver MJ, et al. Gene...Philadelphia, Pennsylvania 19111 REPORT DATE: April 2007 TYPE OF REPORT: Final PREPARED FOR: U.S. Army Medical Research and... TYPE Final 3. DATES COVERED (From - To) 1 Apr 2003 – 31 Mar 2007 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Developing Inhibitors of Ovarian

  14. FY2011 Annual Progress Report for Advanced Combustion Engine Research and Development

    Energy Technology Data Exchange (ETDEWEB)

    none,

    2011-12-01

    Annual Progress Report for the Advanced Combustion Engine Research and Development (R&D) subprogram supporting the mission of the Vehicle Technologies Program by removing the critical technical barriers to commercialization of advanced internal combustion engines (ICEs) for passenger and commercial vehicles that meet future federal emissions regulations.

  15. Advanced Neutron Source (ANS) Project progress report, FY 1994

    Energy Technology Data Exchange (ETDEWEB)

    Campbell, J.H.; King-Jones, K.H. [eds.; Selby, D.L.; Harrington, R.M. [Oak Ridge National Lab., TN (United States); Thompson, P.B. [Martin Marietta Energy Systems, Inc., Oak Ridge, TN (United States). Central Engineering Services

    1995-01-01

    The President`s budget request for FY 1994 included a construction project for the Advanced Neutron Source (ANS). However, the budget that emerged from the Congress did not, and so activities during this reporting period were limited to continued research and development and to advanced conceptual design. A significant effort was devoted to a study, requested by the US Department of Energy (DOE) and led by Brookhaven National Laboratory, of the performance and cost impacts of reducing the uranium fuel enrichment below the baseline design value of 93%. The study also considered alternative core designs that might mitigate those impacts. The ANS Project proposed a modified core design, with three fuel elements instead of two, that would allow operation with only 50% enriched uranium and use existing fuel technology. The performance penalty would be 15--20% loss of thermal neutron flux; the flux would still just meet the minimum design requirement set by the user community. At the time of this writing, DOE has not established an enrichment level for ANS, but two advisory committees have recommended adopting the new core design, provided the minimum flux requirements are still met.

  16. Advanced Neutron Source (ANS) Project progress report, FY 1994

    International Nuclear Information System (INIS)

    Campbell, J.H.; King-Jones, K.H.; Thompson, P.B.

    1995-01-01

    The President's budget request for FY 1994 included a construction project for the Advanced Neutron Source (ANS). However, the budget that emerged from the Congress did not, and so activities during this reporting period were limited to continued research and development and to advanced conceptual design. A significant effort was devoted to a study, requested by the US Department of Energy (DOE) and led by Brookhaven National Laboratory, of the performance and cost impacts of reducing the uranium fuel enrichment below the baseline design value of 93%. The study also considered alternative core designs that might mitigate those impacts. The ANS Project proposed a modified core design, with three fuel elements instead of two, that would allow operation with only 50% enriched uranium and use existing fuel technology. The performance penalty would be 15--20% loss of thermal neutron flux; the flux would still just meet the minimum design requirement set by the user community. At the time of this writing, DOE has not established an enrichment level for ANS, but two advisory committees have recommended adopting the new core design, provided the minimum flux requirements are still met

  17. Clinicopathologic significance of HLA-G and HLA-E molecules in Tunisian patients with ovarian carcinoma.

    Science.gov (United States)

    Babay, Wafa; Ben Yahia, Hamza; Boujelbene, Nadia; Zidi, Nour; Laaribi, Ahmed Baligh; Kacem, Dhikra; Ben Ghorbel, Radhia; Boudabous, Abdellatif; Ouzari, Hadda-Imene; Rizzo, Roberta; Rebmann, Vera; Mrad, Karima; Zidi, Inès

    2018-06-01

    The human leukocyte antigen (HLA)-G and HLA-E, non classical HLA class I molecules, have been highly implicated in immune tolerance. HLA-G and HLA-E molecules were proposed as putative markers of several advanced cancers. As a step towards a better understanding of ovarian carcinoma, we evaluated the expression of both HLA-G and HLA-E molecules and explored their prognostic implication. HLA-G and HLA-E expression were studied by immunohistochemistry on ovarian carcinoma tissues. This expression was semi-quantitatively scored into four expression groups and correlated to clinicopathological parameters and patients' survival. HLA-G and HLA-E have been found to be highly expressed in ovarian carcinoma tissues (Respectively, 72.4% and 96.8%). They are frequently co-expressed. Univariate and multivariate analysis revealed that a positive HLA-G expression status in tumor tissue is a promising candidate parameter to predict disease recurrence in addition to the disease status in Tunisian patients with ovarian carcinoma. Moreover, the elevated HLA-E expression was associated with serous ovarian carcinoma subtype as well as with advanced stages of ovarian carcinoma. HLA-G and HLA-E are highly represented in ovarian carcinoma suggesting a potential association with progressive disease mechanism. HLA-G and HLA-E molecules might be new candidates' markers for ovarian carcinoma progression. Copyright © 2018 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  18. Advanced Industrial Materials (AIM) Program. Annual progress report, FY 1994

    Energy Technology Data Exchange (ETDEWEB)

    Sorrell, C.A.

    1995-05-01

    The Advanced Industrial Materials Program is a part of the Office of Industrial Technologies (OIT), Energy Efficiency and Renewable Energy in the Department of Energy. The mission of the AIM Program is to conduct applied research, development, and applications engineering work, in partnership with industry, to commercialize new or improved materials and materials processing methods that will improve energy efficiency, productivity, and competitiveness. AIM is responsible for identifying, supporting, and coordinating multidisciplinary projects to solve identified industrial needs and transferring the technology to the industrial sector. Program investigators in the DOE National Laboratories are working closely with approximately 100 companies, including 15 partners in Cooperative Research and Development Agreements. Work is being done in a wide variety of materials technologies, including intermetallic alloys, ceramic composites, metal composites, polymers, engineered porous materials, and surface modification. The Program supports other efforts in the Office of Industrial Technologies to assist the energy consuming process industries, including forest products, glass, steel, aluminum, foundries, chemicals, and refineries. To support OITs {open_quotes}Industries of the Future{close_quotes} initiatives and to improve the relevance of materials research, assessments of materials needs and opportunities in the process industries are being made. These assessments are being used for program planning and priority setting; support of work to satisfy those needs is being provided. Many new materials that have come into the marketplace in recent years, or that will be available for commercial use within a few more years, offer substantial benefits to society. This document contains 28 reports on advanced materials research. Individual reports have been processed separately for entry onto the Department of Energy databases.

  19. Advanced Industrial Materials (AIM) program. Annual progress report. FY 1996

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-04-01

    The Advanced Industrial Materials (AIM) Program underwent a major transformation in Fiscal Year 1995 and these changes have continued to the present. When the Program was established in 1990 as the Advanced Industrial Concepts (AIC) Materials Program, the mission was to conduct applied research and development to bring materials and processing technologies from the knowledge derived from basic research to the maturity required for the end use sectors for commercialization. In 1995, the Office of Industrial Technologies (OIT) made radical changes in structure and procedures. All technology development was directed toward the seven `Vision Industries` that use about 80% of industrial energy and generated about 90% of industrial wastes. These are: aluminium; chemical; forest products; glass; metal casting; refineries; and steel. OIT is working with these industries, through appropriate organizations, to develop Visions of the desired condition of each industry some 20 or 25 years in the future and then to prepare Road Maps and Implementation Plans to enable them to reach their goals. The mission of AIM has, therefore, changed to `Support development and commercialization of new or improved materials to improve productivity, product quality, and energy efficiency in the major process industries.` Though AIM remains essentially a National Laboratory Program, it is necessary that each project have industrial partners, including suppliers to, and customers of, the seven industries. Now, well into FY 1996, the transition is nearly complete and the AIM Program remains healthy and productive, thanks to the superb investigators and Laboratory Program Managers. Separate abstracts have been indexed into the energy database for articles from this report.

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

    International Nuclear Information System (INIS)

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

    2012-01-01

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

  1. Silk-microfluidics for advanced biotechnological applications: A progressive review.

    Science.gov (United States)

    Konwarh, Rocktotpal; Gupta, Prerak; Mandal, Biman B

    2016-01-01

    Silk based biomaterials have not only carved a unique niche in the domain of regenerative medicine but new avenues are also being explored for lab-on-a-chip applications. It is pertinent to note that biospinning of silk represents nature's signature microfluidic-maneuver. Elucidation of non-Newtonian flow of silk in the glands of spiders and silkworms has inspired researchers to fabricate devices for continuous extrusion and concentration of silk. Microfluidic channel networks within porous silk scaffolds ensure optimal nutrient and oxygen supply apart from serving as precursors for vascularization in tissue engineering applications. On the other hand, unique topographical features and surface wettability of natural silk fibers have inspired development of a number of simple and cost-effective devices for applications like blood typing and chemical sensing. This review mirrors the recent progress and challenges in the domain of silk-microfluidics for prospective avant-garde applications in the realm of biotechnology. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Progress in LHCD: a tool for advanced regimes on ITER

    Energy Technology Data Exchange (ETDEWEB)

    Tuccillo, A. A.

    2005-07-01

    Since the early 80s, Lower Hybrid (LH) waves have driven plasma current non-inductively in tokamak experiments with efficiency far higher than other auxiliary systems, especially at low plasma temperature. The latter aspect makes LH the natural candidate for off axis current drive (CD) in ITER where current profile control will be required to maintain burning performance on a long time scale. The difficulties in coupling LH waves in high performance H-mode plasmas led in the 90s to the decision, by the ITER JCT, of not supporting directly the development of a LH system, with subsequent exclusion of LH from ITER initial Hn and CD systems. Nevertheless, the LH activity continued in all areas: theory, experiments, modelling and R and D. Recently, in JET, the problem of coupling LH waves in severe edge conditions (ELMy plasmas and very low SOL densities) has been solved by localised gas injection. LH has then boosted the research on advanced scenarios allowing a variety of current profiles, from peaked to deeply hollow, to be used in generating Internal Transport Barriers (ITBs). In JET, long ITBs (11s) have been sustained for times close to the resistive time scale in full CD conditions, additionally pulses lasting minutes, relying on LHCD, are routinely obtained in Tore Supra. Advanced scenarios have also been obtained in conditions of dominant electron heating (FTU, Tore Supra) and efficient CD has been demonstrated at ITER relevant densities on FTU. In these experiments, an improvement of the Electron Cyclotron (EC) CD efficiency (up to 4?) due to synergy with LH is also observed both in normal operation and with EC resonating at a down shifted frequency. Modelling all these experiments has been a good test bench for LH codes and has increased the confidence in their use to predict future experiments. The use of LH as an actuator for Real Time Control of the plasma current profile has become a powerful tool to optimise ITB dynamics in JET and JT-60U. An LH system

  3. Combination Efficacy of Astragalus membranaceus and Curcuma wenyujin at Different Stages of Tumor Progression in an Imageable Orthotopic Nude Mouse Model of Metastatic Human Ovarian Cancer Expressing Red Fluorescent Protein.

    Science.gov (United States)

    Yin, Gang; Tang, Decai; Dai, Jianguo; Liu, Min; Wu, Mianhua; Sun, Y U; Yang, Zhijian; Hoffman, Robert M; Li, Lin; Zhang, Shuo; Guo, Xiuxia

    2015-06-01

    The present study determined the efficacy of extracts of Astragalus membranaceus (AM) and Curcuma wenyujin (CW), a traditional Chinese medicine herbal mixture, at different tumor stages of an orthotopic nude mouse model of human ovarian cancer expressing red fluorescent protein. The tumor-bearing mice were treated with cisplatinum (CDDP), AM, CW, or a combination of AM and CW in each of three tumor stages, using the same regimen. Group 1 received saline as negative control. Group 2 received CDDP i.p. as positive control with a dose of 2 mg/kg, every three days. Group 3 received AM daily via oral gavage, at a dose of 9120 mg/kg. Group 4 received CW daily via oral gavage, at a dose of 4560 mg/kg. Groups 5, 6 and 7 received combinations of AM and CW daily via oral gavage at low (AM, 2280 mg/kg; CW, 1140 mg/kg), medium (AM, 4560 mg/kg; CW 2280 mg/kg), and high (AM, 9120 mg/kg; CW, 4560 mg/kg) doses. The expression of angiogenesis- and apoptosis-related genes in the tumors were analyzed by immunohistochemistry for matrix metalloproteinase 2 (MMP-2), vascular endothelial growth factor (VEGF) fibroblast growth factor 2 (FGF-2), B-cell lymphoma 2 (Bcl-2) and cyclooxygenase 2 (Cox-2), and by polymerase chain reaction for MMP-2, FGF-2 and Bcl-2. CDDP, AM, and its combination with CW-induced significant growth inhibition of Stage I tumors. Strong efficacy of the combination of AM and CW at high dose was observed. Monotherapy with CDDP, AM, CW, and the combination treatments did not significantly inhibit Stage II and III tumors. The expression of MMP-2, VEGF, FGF-2, and Cox-2 was significantly reduced in Stage I tumors treated with AM, CW, and their combination, suggesting a possible role of these angiogenesis- and apoptosis-related genes in the observed efficacy of the agents tested. This study is the first report on the efficacy of anticancer agents at different stages of ovarian cancer in an orthotopic mouse model. As the tumor progressed, it became treatment

  4. Advanced Industrial Materials (AIM) Program annual progress report, FY 1997

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-05-01

    The Advanced Industrial Materials (AIM) Program is a part of the Office of Industrial Technologies (OIT), Energy Efficiency and Renewable Energy, US Department of Energy (DOE). The mission of AIM is to support development and commercialization of new or improved materials to improve energy efficiency, productivity, product quality, and reduced waste in the major process industries. OIT has embarked on a fundamentally new way of working with industries--the Industries of the Future (IOF) strategy--concentrating on the major process industries that consume about 90% of the energy and generate about 90% of the waste in the industrial sector. These are the aluminum, chemical, forest products, glass, metalcasting, and steel industries. OIT has encouraged and assisted these industries in developing visions of what they will be like 20 or 30 years into the future, defining the drivers, technology needs, and barriers to realization of their visions. These visions provide a framework for development of technology roadmaps and implementation plans, some of which have been completed. The AIM Program supports IOF by conducting research and development on materials to solve problems identified in the roadmaps. This is done by National Laboratory/industry/university teams with the facilities and expertise needed to develop new and improved materials. Each project in the AIM Program has active industrial participation and support.

  5. A progress report on DOE's advanced hydropower turbine systems program

    International Nuclear Information System (INIS)

    Sale, M.J.; Cada, G.F.; Rinehart, B.E.

    1997-01-01

    Recent hydropower research within the U.S. Department of Energy (DOE) has focused on the development of new turbine designs that can produce hydroelectricity without such adverse environmental affects as fish entrainment/impingement or degradation of water quality. In partnership with the hydropower industry, DOE's advanced turbine program issued a Request for Proposals for conceptual designs in October 1994. Two contracts were awarded for this initial program phase, work on which will be complete this year. A technical advisory committee with representatives from industry, regulatory agencies, and natural resource agencies was also formed to guide the DOE turbine research. The lack of quantitative biological performance criteria was identified by the committee as a critical knowledge gap. To fill this need, a new literature review was completed on the mechanisms of fish mortality during turbine passage (e.g., scrape/strike, shear, press change, etc.), ways that fish behavior affects their location and orientation in turbines, and how these turbine passage stresses can be measured. Thus year, new Laboratory tests will be conducted on fish response to shear, the least-well understood mechanism of stress. Additional testing of conceptual turbine designs depends on the level of federal funding for this program

  6. Folates in plants: research advances and progress in crop biofortification

    Science.gov (United States)

    Gorelova, Vera; Ambach, Lars; Rébeillé, Fabrice; Stove, Christophe; Van Der Straeten, Dominique

    2017-03-01

    Folates, also known as B9 vitamins, serve as donors and acceptors in one-carbon (C1) transfer reactions. The latter are involved in synthesis of many important biomolecules, such as amino acids, nucleic acids and vitamin B5. Folates also play a central role in the methyl cycle that provides one-carbon groups for methylation reactions. The important functions fulfilled by folates make them essential in all living organisms. Plants, being able to synthesize folates de novo, serve as an excellent dietary source of folates for animals that lack the respective biosynthetic pathway. Unfortunately, the most important staple crops such as rice, potato and maize are rather poor sources of folates. Insufficient folate consumption is known to cause severe developmental disorders in humans. Two approaches are employed to fight folate deficiency: pharmacological supplementation in the form of folate pills and biofortification of staple crops. As the former approach is considered rather costly for the major part of the world population, biofortification of staple crops is viewed as a decent alternative in the struggle against folate deficiency. Therefore strategies, challenges and recent progress of folate enhancement in plants will be addressed in this review. Apart from the ever-growing need for the enhancement of nutritional quality of crops, the world population faces climate change catastrophes or environmental stresses, such as elevated temperatures, drought, salinity that severely affect growth and productivity of crops. Due to immense diversity of their biochemical functions, folates take part in virtually every aspect of plant physiology. Any disturbance to the plant folate metabolism leads to severe growth inhibition and, as a consequence, to a lower productivity. Whereas today’s knowledge of folate biochemistry can be considered very profound, evidence on the physiological roles of folates in plants only starts to emerge. In the current review we will discuss the

  7. Baseline clinical predictors of antitumor response to the PARP inhibitor olaparib in germline BRCA1/2 mutated patients with advanced ovarian cancer.

    Science.gov (United States)

    Rafii, Saeed; Gourley, Charlie; Kumar, Rajiv; Geuna, Elena; Ern Ang, Joo; Rye, Tzyvia; Chen, Lee-May; Shapira-Frommer, Ronnie; Friedlander, Michael; Matulonis, Ursula; De Greve, Jacques; Oza, Amit M; Banerjee, Susana; Molife, L Rhoda; Gore, Martin E; Kaye, Stan B; Yap, Timothy A

    2017-07-18

    The PARP inhibitor olaparib was recently granted Food and Drug Administration (FDA) accelerated approval in patients with advanced BRCA1/2 mutation ovarian cancer. However, antitumor responses are observed in only approximately 40% of patients and the impact of baseline clinical factors on response to treatment remains unclear. Although platinum sensitivity has been suggested as a marker of response to PARP inhibitors, patients with platinum-resistant disease still respond to olaparib. 108 patients with advanced BRCA1/2 mutation ovarian cancers were included. The interval between the end of the most recent platinum chemotherapy and PARPi (PTPI) was used to predict response to olaparib independent of conventional definition of platinum sensitivity. RECIST complete response (CR) and partial response (PR) rates were 35% in patients with platinum-sensitive versus 13% in platinum-resistant (p<0.005). Independent of platinum sensitivity status, the RECIST CR/PR rates were 42% in patients with PTPI greater than 52 weeks and 18% in patients with PTPI less than 52 weeks (p=0.016). No association was found between baseline clinical factors such as FIGO staging, debulking surgery, BRCA1 versus BRCA2 mutations, prior history of breast cancer and prior chemotherapy for breast cancer, and the response to olaparib. We conducted an international multicenter retrospective study to investigate the association between baseline clinical characteristics of patients with advanced BRCA1/2 mutation ovarian cancers from eight different cancer centers and their antitumor response to olaparib. PTPI may be used to refine the prediction of response to PARP inhibition based on the conventional categorization of platinum sensitivity.

  8. Ovarian Disorders

    Science.gov (United States)

    ... a pregnancy can occur. Ovaries also make the female hormones estrogen and progesterone. When a woman goes through menopause, her ovaries stop making those hormones and releasing eggs. Problems with the ovaries include Ovarian cancer Ovarian ...

  9. Treatment Results of Ovarian Dysqerminoma

    International Nuclear Information System (INIS)

    Chung, Eun Ji; Suh, Chang Ok; Seong, Jin Sil; Keum, Ki Chang; Kim, Gwi Eon

    1996-01-01

    Purpose : We tried to evaluate the clinical characteristics, the treatment methods, the results of treatments, and the patterns of failure in ovarian dysgerminoma retrospectively. According to the results we would like to suggest the proper management guideline of stage la ovarian dysgerminoma patients who want to maintain fertility. Methods and Materials : Between 1975 and 1990, 34 patients with ovarian dysgerminoma were treated at the Yonsei University Hospital. The case records of these patients have been reviewed for presenting symptoms, treatment methods, local control, and survival following treatment. Excluded from analysis were five patients with mixed ovarian germ cell tumors and gonadoblastomas (46,XY). Treatment results of the twenty nine patients were analysed by each treatment modality. Twenty one patients were treated with surgery and postoperative adjuvant radiotherapy(group 1). The other eight patients were treated with operation alone (group 2). The median age of twenty-nine patients was 23 years with a range of 8 to 39 years. Presenting symptoms were abdominal mass(20), pelvic discomfort or pain(5) et al. Radiotherapy was performed by 10MV LINAC or Co-60 teletherapy unit. The total radiation dose of the whole abdomen was 20-25 Gy/3 weeks, 1-1.5 Gy/fraction with a boost to the whole pelvis 10-15 Gy / 1-2 weeks1.8-2.0 Gy/fraction. Advanced stage disease (stage II or stage III) patients received prophylactic mediastinal and supraclavicular irradiation to a dose of 16-26 Gy. Median duration of follow-up of living patients was 80 months (range : 13-201 months). Results : All of the twenty one patients of group 1 were alive without disease (100%). Among the eight patients who were not treated with radiotherapy (group 2), six patients developed local recurrence. Four patients referred with recurrent disease were treated with salvage radiotherapy. Three of four patients were salvaged and one patient who had recurrent intra-abdominal disease died of

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

    Directory of Open Access Journals (Sweden)

    Anne Marszalek

    2010-01-01

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

  11. En-bloc pelvic resection with concomitant rectosigmoid colectomy and immediate anastomosis as part of primary cytoreductive surgery for patients with advanced ovarian cancer.

    Science.gov (United States)

    Yildirim, Y; Ertas, I E; Nayki, U; Ulug, P; Nayki, C; Yilmaz, I; Gultekin, E; Dogan, A; Aykas, A; Ulug, S; Ozdemir, A; Solmaz, U

    2014-01-01

    To assess the authors' experiences in en bloc pelvic resection with concomitant rectosigmoid colectomy and primary anastomosis as a part of primary cytoreductive surgery for patients with advanced ovarian cancer. Atotal of 22 patients with FIGO Stage IIB-IV epithelial ovarian cancer who underwent en bloc pelvic resection with anastomosis were retrospectively reviewed. Data analyses were carried out using SPSS 10.0 and descriptive statistics, Kaplan-Meier survival curves, and Log Rank (Mantel-Cox) test were used for statistical estimations. Median age was 58.8 years. FIGO stage distribution of the patients was; one (4.5%) IIB, three (13.7%) IIC, three (13.7%) IIIA, six (27.3%) IIIB, and nine (40.9%) IIIC. Median peritoneal cancer index (PCI) was 8 (range 5-22) and optimal cytoreduction was achieved in 18 patients (81.8%) of whom 13 (59.1%) had no macroscopic residual disease (complete cytoreduction). There was no perioperative mortality. A total of nine complications occurred in seven (31.8%) patients. Anastomotic leakage was observed in one (4.5%) patient. There was no re-laparotomy. Mean follow-up time was 60 months. There were 15 (68.2%) recurrences of which 12 (80%) presented in extra-pelvic localizations. Mean disease-free survival (DFS) and overall survival (OVS) were estimated as 43.6 and 50.5 months, respectively. Patients with complete cytoreduction had a better DFS (p = 0.006) and OVS (p = 0.003) than those with incomplete cytoreduction. En bloc pelvic resection, as a part of surgical cytoreduction, seems to be a safe and effective procedure in many patients with advanced ovarian cancer if required. Despite relatively high general complication rate, anastomosis-related morbidity of this procedure is low as 0.8%. Nevertheless, surgical plan and perioperative care should be personalized according to medical and surgical conditions of the patient.

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

    DEFF Research Database (Denmark)

    du Bois, Andreas; Kristensen, Gunnar; Ray-Coquard, Isabelle

    2016-01-01

    BACKGROUND: Angiogenesis is a target in the treatment of ovarian cancer. Nintedanib, an oral triple angiokinase inhibitor of VEGF receptor, platelet-derived growth factor receptor, and fibroblast growth factor receptor, has shown activity in phase 2 trials in this setting. We investigated the com...

  13. FY2009 Annual Progress Report for Advanced Combustion Engine Research and Development

    Energy Technology Data Exchange (ETDEWEB)

    none,

    2009-12-01

    Fiscal Year 2009 Annual Progress Report for the Advanced Combustion Engine Research and Development (R&D) subprogram. The Advanced Combustion Engine R&D subprogram supports the mission of the VTP program by removing the critical technical barriers to commercialization of advanced internal combustion engines (ICEs) for passenger and commercial vehicles that meet future Federal emissions regulations. Dramatically improving the efficiency of ICEs and enabling their introduction in conventional as well as hybrid electric vehicles is the most promising and cost-effective approach to increasing vehicle fuel economy over the next 30 years.

  14. New Rule Use Drives the Relation between Working Memory Capacity and Raven's Advanced Progressive Matrices

    Science.gov (United States)

    Wiley, Jennifer; Jarosz, Andrew F.; Cushen, Patrick J.; Colflesh, Gregory J. H.

    2011-01-01

    The correlation between individual differences in working memory capacity and performance on the Raven's Advanced Progressive Matrices (RAPM) is well documented yet poorly understood. The present work proposes a new explanation: that the need to use a new combination of rules on RAPM problems drives the relation between performance and working…

  15. Progress of Journal‘Advanced Technology of Electrical Engineering and Energy’

    Institute of Scientific and Technical Information of China (English)

    QIN Jie; LIN Liang-zhen; QI Zhi-ping; MA Yu-huan; SHEN Guo-liao; JING Bo-hong

    2009-01-01

    The paper has introduced the Journal 'Advanced Technology of Electrical Engineering and Energy', presented its main journal evaluation indexes. The result indicates that the journal has made great progress in recent years. It gives much info. about the journal to authors.

  16. Accuracy of MDCT in the preoperative definition of Peritoneal Cancer Index (PCI) in patients with advanced ovarian cancer who underwent peritonectomy and hyperthermic intraperitoneal chemotherapy (HIPEC).

    Science.gov (United States)

    Mazzei, Maria Antonietta; Khader, Leila; Cirigliano, Alfredo; Cioffi Squitieri, Nevada; Guerrini, Susanna; Forzoni, Beatrice; Marrelli, Daniele; Roviello, Franco; Mazzei, Francesco Giuseppe; Volterrani, Luca

    2013-12-01

    To evaluate the accuracy of MDCT in the preoperative definition of Peritoneal Cancer Index (PCI) in patients with advanced ovarian cancer who underwent a peritonectomy and hyperthermic intraperitoneal chemotherapy (HIPEC) after neoadjuvant chemotherapy to obtain a pre-surgery prognostic evaluation and a prediction of optimal cytoreduction surgery. Pre-HIPEC CT examinations of 43 patients with advanced ovarian cancer after neoadjuvant chemotherapy were analyzed by two radiologists. The PCI was scored according to the Sugarbaker classification, based on lesion size and distribution. The results were compared with macroscopic and histologic data after peritonectomy and HIPEC. To evaluate the accuracy of MDCT to detect and localize peritoneal carcinomatosis, both patient-level and regional-level analyses were conducted. A correlation between PCI CT and histologic values for each patient was searched according to the PCI grading. Considering the patient-level analysis, CT shows a sensitivity, specificity, PPV, NPV, and an accuracy in detecting the peritoneal carcinomatosis of 100 %, 40 %, 93 % 100 %, and 93 %, respectively. Considering the regional level analysis, a sensitivity, specificity, PPV, NPV, and diagnostic accuracy of 72 %, 80 %, 66 %, 84 %, and 77 %, respectively were obtained for the correlation between CT and histology. Our results encourage the use of MDCT as the only technique sufficient to select patients with peritoneal carcinomatosis for cytoreductive surgery and HIPEC on the condition that a CT examination will be performed using a dedicated protocol optimized to detect minimal peritoneal disease and CT images will be analyzed by an experienced reader.

  17. 2000 Annual Progress Report for Fuels for Advanced CIDI Engines and Fuel Cells

    Energy Technology Data Exchange (ETDEWEB)

    Chalk, S.

    2000-12-11

    The Department of Energy's Office of Transportation Technologies Fiscal Year (FY) 2000 Annual Progress Report for the Fuels for Advanced CIDI Engines and Fuel Cells Program highlights progress achieved during FY 2000 and comprises 22 summaries of industry and National Laboratory projects that were conducted. The report provides an overview of the exciting work being conducted to tackle the tough technical challenges associated with developing clean burning fuels that will enable meeting the performance goals of the Emission Control R and D for Advanced CIDI Engines and the Transportation Fuel Cell Power Systems Programs. The summaries cover the effects of CIDI engine emissions and fuel cell power system performance, the effects of lubricants on engine emissions, the effects of fuel and consumed lubricants on exhaust emission control devices and the health and safety, materials compatibility, and economics of advanced petroleum-based fuels.

  18. Associations Between Vitamin D Intake and Progression to Incident Advanced Age-Related Macular Degeneration.

    Science.gov (United States)

    Merle, Bénédicte M J; Silver, Rachel E; Rosner, Bernard; Seddon, Johanna M

    2017-09-01

    There is growing evidence of the importance of nutrition in age-related macular degeneration (AMD), but no prospective studies have explored the impact of vitamin D. We evaluated the association between vitamin D intake and progression to advanced AMD. Among 2146 participants (3965 eyes), 541 (777 eyes) progressed from early or intermediate AMD to advanced disease (mean follow-up: 9.4 years) based on ocular imaging. Nutrients were log transformed and calorie adjusted. Survival analysis was used to assess associations between incident advanced disease and vitamin D intake. Neovascular disease (NV) and geographic atrophy (GA) were evaluated separately. Combined effects of dietary vitamin D and calcium were assessed based on high or low consumption of each nutrient. There was a lower risk of progression to advanced AMD in the highest versus lowest quintile of dietary vitamin D intake after adjustment for demographic, behavioral, ocular, and nutritional factors (hazard ratio [HR]: 0.60; 95% confidence interval [CI]: 0.43-0.83; P trend = 0.0007). Similar results were observed for NV (HR: 0.59; 95% CI: 0.39-0.89; P trend = 0.005) but not GA (HR: 0.83; 95% CI: 0.53-1.30; P trend = 0.35). A protective effect was observed for advanced AMD among participants with high vitamin D and low calcium compared to the group with low levels for each nutrient (HR: 0.67; 95% CI: 0.50-0.88; P = 0.005). When supplement use was considered, the effect was in the protective direction but was not significant. A diet rich in vitamin D may prevent or delay progression to advanced AMD, especially NV. Additional exploration is needed to elucidate the potential protective role of vitamin D and its contribution to reducing visual loss.

  19. Staging and treatment of ovarian carcinoma

    International Nuclear Information System (INIS)

    De Palo, G.; Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan

    1989-01-01

    The staging and treatment of ovarian cancer is reviewed with special attention to developments during the last decade. Pathways of spread, presurgical and surgical staging are described and discussed, as are the biologic characters of the different histologic subtypes. Principles of surgery, endoperitoneal and external radiotherapy, single-drug and multiple-drug systemic chemotherapy (therapeutic and adjuvant), intraperitoneal chemotherapy, second-line chemotherapy, hormone therapy and the use of biologic response modifiers are reported and discussed with background of recent clinical trials. It is concluded that considerable progress has been made concerning diagnosis, staging and treatment of ovarian cancer. The proportion of cases in advanced stages has thus decreased and the survival rate increased. However, it is also obvious that the long-term prognosis for patients with advanced disease has not significantly improved over the last 10 years, despite introduction of multiple-drug regimens with high initial response rates. Ovarian cancer remains the most important gynecologic cause of death in the Western countries. (orig.)

  20. Research and Development Progress of National Key Laboratory of Advanced Composites on Advanced Aeronautical Resin Matrix Composites

    Directory of Open Access Journals (Sweden)

    LI Bintai

    2016-06-01

    Full Text Available Applications and research progress in advanced aeronautical resin matrix composites by National Key Laboratory of Advanced Composites (LAC were summarized. A novel interlaminar toughening technology employing ultra-thin TP non-woven fabric was developed in LAC, which significantly improved the compression after impact (CAI performances of composite laminates.Newly designed multilayer sandwich stealth composite structures exhibited a good broadband radar absorbing properties at 1-18 GHz.There were remarkable developments in high toughness and high temperature resin matrix composites, covering major composite processing technologies such as prepreg-autoclave procedure, liquid composite molding and automation manufacture, etc. Finally, numerical simulation and optimization methods were deliberately utilized in the study of composites curing behavior, resin flow and curing deformation. A composite material database was also established.In conclusion, LAC has been a great support for the development of aeronautical equipment, playing such roles as innovation leading, system dominating, foundation supporting and application ensuring of aerocomposites.

  1. FY2016 Advanced Batteries R&D Annual Progress Report - Part 5 of 5

    Energy Technology Data Exchange (ETDEWEB)

    None, None

    2017-08-31

    The Advanced Batteries research and development (R&D) subprogram within the DOE Vehicle Technologies Office (VTO) provides support and guidance for projects focusing on batteries for plug-in electric vehicles. Program targets focus on overcoming technical barriers to enable market success including: (1) significantly reducing battery cost, (2) increasing battery performance (power, energy, durability), (3) reducing battery weight & volume, and (4) increasing battery tolerance to abusive conditions such as short circuit, overcharge, and crush. This report describes the progress made on the research and development projects funded by the Battery subprogram in 2016. This section cover Advanced Battery Materials Research (BMR) part 2, Battery500 Innovation Centers project summaries, and appendices.

  2. Potential mechanisms of disease progression and management of advanced-phase chronic myeloid leukemia

    Science.gov (United States)

    Jabbour, Elias J.; Hughes, Timothy P.; Cortés, Jorge E.; Kantarjian, Hagop M.; Hochhaus, Andreas

    2014-01-01

    Despite vast improvements in treatment of Philadelphia chromosome–positive chronic myeloid leukemia (CML) in chronic phase (CP), advanced stages of CML, accelerated phase or blast crisis, remain notoriously difficult to treat. Treatments that are highly effective against CML-CP produce disappointing results against advanced disease. Therefore, a primary goal of therapy should be to maintain patients in CP for as long as possible, by (1) striving for deep, early molecular response to treatment; (2) using tyrosine kinase inhibitors that lower risk of disease progression; and (3) more closely observing patients who demonstrate cytogenetic risk factors at diagnosis or during treatment. PMID:24050507

  3. FY2016 Advanced Batteries R&D Annual Progress Report - Part 4 of 5

    Energy Technology Data Exchange (ETDEWEB)

    None, None

    2017-08-31

    The Advanced Batteries research and development (R&D) subprogram within the DOE Vehicle Technologies Office (VTO) provides support and guidance for projects focusing on batteries for plug-in electric vehicles. Program targets focus on overcoming technical barriers to enable market success including: (1) significantly reducing battery cost, (2) increasing battery performance (power, energy, durability), (3) reducing battery weight & volume, and (4) increasing battery tolerance to abusive conditions such as short circuit, overcharge, and crush. This report describes the progress made on the research and development projects funded by the Battery subprogram in 2016. This section covers Advanced Battery Materials Research (BMR) part 1.

  4. The association between body composition and toxicities from the combination of Doxil and trabectedin in patients with advanced relapsed ovarian cancer.

    Science.gov (United States)

    Prado, Carla M M; Baracos, Vickie E; Xiao, Jingjie; Birdsell, Laura; Stuyckens, Kim; Park, Youn Choi; Parekh, Trilok; Sawyer, Michael B

    2014-06-01

    Emerging research suggests that body composition can predict toxicity of certain chemotherapeutic agents. We used data from a clinical study to investigate associations between body composition and combined DOXIL (pegylated liposomal doxorubicin; PLD) and trabectedin (Yondelis) treatment, an effective treatment for ovarian cancer that shows high interpatient variation in toxicity profile. Patients (n = 74) participating in a phase III randomized trial of relapsed advanced ovarian cancer receiving PLD (30 mg/m(2)) and trabectedin (1.1 mg/m(2)) were included. Muscle tissue was measured by analysis of computerized tomography images, and an extrapolation of muscle and adipose tissue to lean body mass (LBM) and fat mass (FM) were employed. Toxicity profile after cycle 1 was used and graded according to the National Cancer Institute Common Toxicity Criteria (version 3). Patients presented with a wide range of body composition. In overweight and obese patients (body mass index (BMI) ≥ 25 kg/m(2), n = 48) toxicity was more prevalent in those with lower BMI (p = 0.028) and a lower FM (n = 43, p = 0.034). Although LBM alone was not predictive of toxicity, a lower FM/LBM ratio was the most powerful variable associated with toxicity (p = 0.006). A different pattern emerged among normal weight patients (n = 26) where toxicity was rare among patients with smaller BMI (body weight, with a lower ratio predicting higher exposure and risk for toxicity.

  5. Quality of pathology reports for advanced ovarian cancer: are we missing essential information? An audit of 479 pathology reports from the EORTC-GCG 55971/NCIC-CTG OV13 neoadjuvant trial

    NARCIS (Netherlands)

    Verleye, Leen; Ottevanger, Petronella B.; Kristensen, Gunnar B.; Ehlen, Tom; Johnson, Nick; van der Burg, Maria E. L.; Reed, Nick S.; Verheijen, René H. M.; Gaarenstroom, Katja N.; Mosgaard, Berit; Seoane, Jose M.; van der Velden, Jacobus; Lotocki, Robert; van der Graaf, Winette; Penninckx, Björn; Coens, Corneel; Stuart, Gavin; Vergote, Ignace

    2011-01-01

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

  6. Quality of pathology reports for advanced ovarian cancer: are we missing essential information? An audit of 479 pathology reports from the EORTC-GCG 55971/NCIC-CTG OV13 neoadjuvant trial

    NARCIS (Netherlands)

    Verleye, L.I.A.; Ottevanger, P.B.; Kristensen, G.B.; Ehlen, T.; Johnson, N.; Burg, M.E. van der; Reed, N.S.; Verheijen, R.H.; Gaarenstroom, K.N.; Mosgaard, B.; Seoane, J.M.; Velden, J. Van der; Lotocki, R.; Graaf, W.T.A. van der; Penninckx, B.; Coens, C.; Stuart, G.; Vergote, I.

    2011-01-01

    OBJECTIVE: 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

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

    Directory of Open Access Journals (Sweden)

    Sharifeh Mehrabi

    2014-01-01

    Full Text Available Serous subtype of ovarian cancer is considered to originate from fallopian epithelium mucosa that has been exposed to physiological changes resulting from ovulation. Ovulation influences an increased in inflammation of epithelial ovarian cells as results of constant exposure of cells to ROS. The imbalance between ROS and antioxidant capacities, as well as a disruption of redox signaling, causes a wide range of damage to DNA, proteins, and lipids. This study applied spectrophotometric, dinitrophenylhydrazone (DNPH assay, two-dimensional gel electrophoresis, and Western blot analyses to assess the levels of oxidatively modified proteins in 100 primary serous epithelial ovarian carcinoma and normal/surrounding tissues. These samples were obtained from 56 Caucasian and 44 African-American patients within the age range of 61±10 years. Analyses showed that the levels of reactive protein carbonyl groups increased as stages progressed to malignancy. Additionally, the levels of protein carbonyls in serous ovarian carcinoma among African Americans are 40% (P<0.05 higher relative to Caucasian at similar advanced stages. Results suggest that oxidative stress is involved in the modification of carbonyl protein groups, leading to increased aggressiveness of epithelial ovarian tumors and may contribute to the disease's invasiveness among African Americans.

  8. Low MAD2 expression levels associate with reduced progression-free survival in patients with high-grade serous epithelial ovarian cancer.

    LENUS (Irish Health Repository)

    Furlong, Fiona

    2012-04-01

    Epithelial ovarian cancer (EOC) has an innate susceptibility to become chemoresistant. Up to 30% of patients do not respond to conventional chemotherapy [paclitaxel (Taxol®) in combination with carboplatin] and, of those who have an initial response, many patients relapse. Therefore, an understanding of the molecular mechanisms that regulate cellular chemotherapeutic responses in EOC cells has the potential to impact significantly on patient outcome. The mitotic arrest deficiency protein 2 (MAD2), is a centrally important mediator of the cellular response to paclitaxel. MAD2 immunohistochemical analysis was performed on 82 high-grade serous EOC samples. A multivariate Cox regression analysis of nuclear MAD2 IHC intensity adjusting for stage, tumour grade and optimum surgical debulking revealed that low MAD2 IHC staining intensity was significantly associated with reduced progression-free survival (PFS) (p = 0.0003), with a hazard ratio of 4.689. The in vitro analyses of five ovarian cancer cell lines demonstrated that cells with low MAD2 expression were less sensitive to paclitaxel. Furthermore, paclitaxel-induced activation of the spindle assembly checkpoint (SAC) and apoptotic cell death was abrogated in cells transfected with MAD2 siRNA. In silico analysis identified a miR-433 binding domain in the MAD2 3\\' UTR, which was verified in a series of experiments. Firstly, MAD2 protein expression levels were down-regulated in pre-miR-433 transfected A2780 cells. Secondly, pre-miR-433 suppressed the activity of a reporter construct containing the 3\\'-UTR of MAD2. Thirdly, blocking miR-433 binding to the MAD2 3\\' UTR protected MAD2 from miR-433 induced protein down-regulation. Importantly, reduced MAD2 protein expression in pre-miR-433-transfected A2780 cells rendered these cells less sensitive to paclitaxel. In conclusion, loss of MAD2 protein expression results in increased resistance to paclitaxel in EOC cells. Measuring MAD2 IHC staining intensity may predict

  9. Recent progress in accelerator activities at Raja Ramanna Centre for Advanced Technology, Indore

    International Nuclear Information System (INIS)

    Gupta, P.D.

    2013-01-01

    Raja Ramanna Centre for Advanced Technology, Indore is a premier national institute engaged in R and D work in front-line areas of accelerator science, technology, and applications. The Centre has designed, developed, and commissioned two synchrotron radiation sources: Indus-1 and Indus-2, serving as national facilities. The Centre is pursuing various other accelerator activities viz. development of a high energy proton accelerator for a spallation neutron source, electron accelerators for food irradiation and industrial applications and free electron lasers (FEL) in THz and IR spectral region, study of innovative schemes of laser driven electron acceleration, and development of advanced technologies to support these activities such as superconducting RF (SCRF) technology, cryogenics, RF power, magnets, ultra high vacuum and control instrumentation. In this talk, an overview of the progress made in accelerator activities at Raja Ramanna Centre for Advanced Technology in recent years is be presented

  10. Implementation of Extensive Cytoreduction Resulted in Improved Survival Outcomes for Patients with Newly Diagnosed Advanced-Stage Ovarian, Tubal, and Peritoneal Cancers.

    Science.gov (United States)

    Raspagliesi, Francesco; Bogani, Giorgio; Ditto, Antonino; Martinelli, Fabio; Chiappa, Valentina; Borghi, Chiara; Scaffa, Cono; Morano, Federica; Maltese, Giuseppa; Lorusso, Domenica

    2017-10-01

    Residual disease (RD) after primary debulking surgery (PDS) is one of the main factors driving ovarian cancer prognosis. The primary end point of this study was assessment of the impact that surgery had on survival outcomes for patients with advanced ovarian cancer. Data on the effect of newly diagnosed advanced-stage ovarian, tubal, and peritoneal cancers were analyzed during two study periods (T1: 2001-2006 and T2: 2007-2012), in which the concepts of optimal and complete cytoreduction were introduced and implemented. In this study, 260 patients (36%) had surgery during T1 and 462 patients (64%) had surgery during T2. The rate of PDS increased, from 55.4% (144/260) during T1 to 85.5% (395/462) during T2 (p < 0.001). At the time of PDS, complete resection (RD0) was achieved for 45.1% of the patients during T1 and 76.7% of the patients during T2 (p < 0.001), whereas optimal resection (RD < 1 cm) was achieved for 60.4% of the patients during T1 and 85.3% of the patients during T2 (p < 0.001). Disease-free survival improved during the study periods (p = 0.006). Overall survival was similar in T1 and T2 (p = 0.18). The preoperative CA125 level, disease stage, and RD remained independently associated with disease-free survival (p ≤ 0.05). The performance of interval debulking surgery (IDS) instead of PDS correlated with worse survival outcomes (hazard ratio [HR] 1.47; 95% confidence interval [CI] 1.24-1.92; p = 0.02), whereas achievement of RD0 and RD < 1 cm independently improved overall survival (HR 0.45; 95% CI 0.22-0.91; p = 0.02 for RD0 and HR 0.47; 95% CI 0.23-0.96; p = 0.03 for RD0). The implementation of extensive cytoreduction allows improvement of patient outcomes. Further studies are needed to assess the risk-to-benefit ratio between PDS and IDS and to identify patients who benefit much more from one treatment method than from another.

  11. Liriodenine, an aporphine alkaloid from Enicosanthellum pulchrum, inhibits proliferation of human ovarian cancer cells through induction of apoptosis via the mitochondrial signaling pathway and blocking cell cycle progression.

    Science.gov (United States)

    Nordin, Noraziah; Majid, Nazia Abdul; Hashim, Najihah Mohd; Rahman, Mashitoh Abd; Hassan, Zalila; Ali, Hapipah Mohd

    2015-01-01

    Enicosanthellum pulchrum is a tropical plant from Malaysia and belongs to the Annonaceae family. This plant is rich in isoquinoline alkaloids. In the present study, liriodenine, an isoquinoline alkaloid, was examined as a potential anticancer agent, particularly in ovarian cancer. Liriodenine was isolated by preparative high-performance liquid chromatography. Cell viability was performed to determine the cytotoxicity, whilst the detection of morphological changes was carried out by acridine orange/propidium iodide assay. Initial and late apoptosis was examined by Annexin V-fluorescein isothiocyanate and DNA laddering assays, respectively. The involvement of pathways was detected via caspase-3, caspase-8, and caspase-9 analyses. Confirmation of pathways was further performed in mitochondria using a cytotoxicity 3 assay. Apoptosis was confirmed at the protein level, including Bax, Bcl-2, and survivin, while interruption of the cell cycle was used for final validation of apoptosis. The result showed that liriodenine inhibits proliferation of CAOV-3 cells at 37.3 μM after 24 hours of exposure. Changes in cell morphology were detected by the presence of cell membrane blebbing, chromatin condensation, and formation of apoptotic bodies. Early apoptosis was observed by Annexin V-fluorescein isothiocyanate bound to the cell membrane as early as 24 hours. Liriodenine activated the intrinsic pathway by induction of caspase-3 and caspase-9. Involvement of the intrinsic pathway in the mitochondria could be seen, with a significant increase in mitochondrial permeability and cytochrome c release, whereas the mitochondrial membrane potential was decreased. DNA fragmentation occurred at 72 hours upon exposure to liriodenine. The presence of DNA fragmentation indicates the CAOV-3 cells undergo late apoptosis or final stage of apoptosis. Confirmation of apoptosis at the protein level showed overexpression of Bax and suppression of Bcl-2 and survivin. Liriodenine inhibits progression

  12. Pazopanib Maintenance Therapy in East Asian Women With Advanced Epithelial Ovarian Cancer: Results From AGO-OVAR16 and an East Asian Study.

    Science.gov (United States)

    Kim, Jae-Weon; Mahner, Sven; Wu, Ling-Ying; Shoji, Tadahiro; Kim, Byoung-Gie; Zhu, Jian-Qing; Takano, Tadao; Park, Sang-Yoon; Kong, Bei-Hua; Wu, Qiang; Wang, Kung-Liahng; Ngan, Hextan Ys; Liu, Ji-Hong; Wei, Li-Hui; Mitrica, Ionel; Zhang, Pingkuan; Crescenzo, Rocco; Wang, Qiong; Cox, Charles J; Harter, Philipp; du Bois, Andreas

    2018-01-01

    The recent phase 3 trial AGO-OVAR16 demonstrated that pazopanib maintenance improved median progression-free survival in patients with ovarian cancer whose disease did not progress during first-line treatment. However, this improvement was not seen in the subset of East Asian patients. The current analysis evaluated the efficacy and safety of pazopanib maintenance in East Asian patients from AGO-OVAR16 and a separate East Asian study. East Asian patients from AGO-OVAR16 (n = 209) and the East Asian study (N = 145) were randomized 1:1 to receive pazopanib 800 mg/d or placebo for up to 24 months. The primary end point for each study was progression-free survival by RECIST (Response Evaluation Criteria in Solid Tumors) based on investigator assessment. Clinical and genetics data were analyzed separately by study or pooled according to separate predetermined statistical plans. Pazopanib maintenance had a detrimental effect on median progression-free survival versus placebo in East Asian patients from the combined studies (n = 354; 17.9 vs 21.5 months; hazard ratio, 1.114; 95% confidence interval, 0.818-1.518; P = 0.4928). Pazopanib maintenance showed a disadvantage in overall survival in East Asian patients from AGO-OVAR16 versus placebo (hazard ratio, 1.706; 95% confidence interval, 1.010-2.883; P = 0.0465); overall survival analysis was not performed in the East Asian study because of insufficient event numbers. Pazopanib-treated patients had a significantly higher incidence of grade 3 or higher hypertension (27%) and neutropenia (13%) versus placebo. The treatment effect of maintenance pazopanib in East Asian patients seemed to differ from that in non-Asian patients. In study-specific and pooled analyses, none of the potential factors analyzed could satisfactorily explain the different efficacy results of pazopanib in East Asian patients.

  13. Advanced and rapidly progressing head and neck cancer: good palliation following intralesional bleomycin.

    LENUS (Irish Health Repository)

    Quintyne, Keith Ian

    2011-09-01

    The authors herein report the case of a 61-year-old man undergoing adjuvant therapy for locally advanced laryngeal cancer, who developed parastomal recurrence in his radiation field around his tracheotomy site, while he was undergoing radiation therapy, and compromised the secure placement of his tracheotomy tube and maintenance of his upper airway. MRI restaging and biopsy confirmed recurrence and progressive disease in his mediastinum. He underwent local therapy with intralesional bleomycin with good palliation, and ability to maintain the patency of his upper airway.

  14. FY2016 Advanced Batteries R&D Annual Progress Report - Part 2 of 5

    Energy Technology Data Exchange (ETDEWEB)

    None, None

    2017-08-31

    The Advanced Batteries research and development (R&D) subprogram within the DOE Vehicle Technologies Office (VTO) provides support and guidance for projects focusing on batteries for plug-in electric vehicles. Program targets focus on overcoming technical barriers to enable market success including: (1) significantly reducing battery cost, (2) increasing battery performance (power, energy, durability), (3) reducing battery weight & volume, and (4) increasing battery tolerance to abusive conditions such as short circuit, overcharge, and crush. This report describes the progress made on the research and development projects funded by the Battery subprogram in 2016. This section covers the summaries of the Applied Batteries Research for Transportation Projects part 1.

  15. FY2016 Advanced Batteries R&D Annual Progress Report - Part 3 of 5

    Energy Technology Data Exchange (ETDEWEB)

    None, None

    2017-08-31

    The Advanced Batteries research and development (R&D) subprogram within the DOE Vehicle Technologies Office (VTO) provides support and guidance for projects focusing on batteries for plug-in electric vehicles. Program targets focus on overcoming technical barriers to enable market success including: (1) significantly reducing battery cost, (2) increasing battery performance (power, energy, durability), (3) reducing battery weight & volume, and (4) increasing battery tolerance to abusive conditions such as short circuit, overcharge, and crush. This report describes the progress made on the research and development projects funded by the Battery subprogram in 2016. This section covers the summaries of the Applied Batteries Research for Transportation Projects part 2.

  16. Convergence of advances in genomics, team science, and repositories as drivers of progress in psychiatric genomics.

    Science.gov (United States)

    Lehner, Thomas; Senthil, Geetha; Addington, Anjené M

    2015-01-01

    After many years of unfilled promise, psychiatric genetics has seen an unprecedented number of successes in recent years. We hypothesize that the field has reached an inflection point through a confluence of four key developments: advances in genomics; the orientation of the scientific community around large collaborative team science projects; the development of sample and data repositories; and a policy framework for sharing and accessing these resources. We discuss these domains and their effect on scientific progress and provide a perspective on why we think this is only the beginning of a new era in scientific discovery. Published by Elsevier Inc.

  17. Progress on advanced dc and ac induction drives for electric vehicles

    Science.gov (United States)

    Schwartz, H. J.

    1982-01-01

    Progress is reported in the development of complete electric vehicle propulsion systems, and the results of tests on the Road Load Simulator of two such systems representative of advanced dc and ac drive technology are presented. One is the system used in the DOE's ETV-1 integrated test vehicle which consists of a shunt wound dc traction motor under microprocessor control using a transistorized controller. The motor drives the vehicle through a fixed ratio transmission. The second system uses an ac induction motor controlled by transistorized pulse width modulated inverter which drives through a two speed automatically shifted transmission. The inverter and transmission both operate under the control of a microprocessor. The characteristics of these systems are also compared with the propulsion system technology available in vehicles being manufactured at the inception of the DOE program and with an advanced, highly integrated propulsion system upon which technology development was recently initiated.

  18. Ovarian lymphoma

    International Nuclear Information System (INIS)

    Bonet Fonseca, Ivan; Diaz Anaya, Amnia; Francis, Tabu

    2012-01-01

    50 % of pediatric oncologic pathology corresponds to mass or solid tumors, reaching about 20 % of total abdomen. The tumors that most frequently occur in the abdomen are nephroblastoma or Wilms tumor, Burkitts lymphoma, neuroblastoma, and ovarian germ cell tumors

  19. Ovarian cancer

    Science.gov (United States)

    ... injected directly into the abdominal cavity (intraperitoneal, or IP). Radiation therapy is rarely used to treat ovarian ... About MedlinePlus Site Map FAQs Customer Support Get email updates Subscribe to RSS Follow us Disclaimers Copyright ...

  20. Ovarian Cancer

    Science.gov (United States)

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

  1. Subtypes of Ovarian Cancer and Ovarian Cancer Screening

    Directory of Open Access Journals (Sweden)

    Masafumi Koshiyama

    2017-03-01

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

  2. Subtypes of Ovarian Cancer and Ovarian Cancer Screening.

    Science.gov (United States)

    Koshiyama, Masafumi; Matsumura, Noriomi; Konishi, Ikuo

    2017-03-02

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

  3. Decreased expression of Beclin 1 correlates closely with Bcl-xL expression and poor prognosis of ovarian carcinoma.

    Directory of Open Access Journals (Sweden)

    Huan-Xin Lin

    Full Text Available It has been suggested that autophagy-related Beclin 1 plays a critical role in the regulation of tumor development and/or progression, but its prognostic significance and relationship with Bcl-xL expression in ovarian carcinoma are unclear.In the present study, the methods of Western blotting and immunohistochemistry (IHC were utilized to investigate the expression status of Beclin 1 and Bcl-xL in fresh ovarian tissues and paraffin-embedded epithelial ovarian tumor tissues. Decreased expression of Beclin 1 was examined by IHC in 8.3% of normal ovaries, in 15.4% of cystadenomas, in 20.0% of borderline tumors, and in 55.6% of ovarian carcinomas, respectively. In ovarian carcinomas, decreased expression of Beclin 1 was correlated closely with ascending histological grade, later pT/pN/pM status and/or advanced clinical stage (P<0.05. In univariate survival analysis, a highly significant association between low-expressed Beclin 1 and shortened patient survival was evaluated in ovarian carcinoma patients (P<0.01, and Beclin 1 expression was an independent prognostic factor as evidenced by multivariate analysis (P = 0.013. In addition, decreased expression of Beclin 1 was inversely correlated with altered expression of Bcl-xL in ovarian carcinoma cohort, and combined analysis further showed that the low Beclin 1/high Bcl-xL group had the lowest survival rate.Our findings suggest that Beclin 1 expression, as examined by IHC, could be served as an additional tool in identifying ovarian carcinoma patients at risk of tumor progression, and predicting patient survival in ovarian carcinomas with increased expression of Bcl-xL.

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

    African Journals Online (AJOL)

    ajl yemi

    2011-10-26

    Oct 26, 2011 ... 10%) subtypes (Kristensen et al., 2003; Green et al.,. 1999). The disease ... history of ovarian and/or breast cancer, and nulliparity, whereas the oral ... and molecular mechanisms of ovarian cancer remain unclear. It is most ..... chemotherapy on the prognosis in advanced epithelial ovarian cancer. N. Engl.

  5. 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

  6. Advanced converter technology. Technical progress report, May 23, 1979-May 22, 1980

    Energy Technology Data Exchange (ETDEWEB)

    Banic, C. V.; Eckhouse, S. A.; Kornbrust, F. J.; Lipman, K.; Peterson, J. L.; Rosati, R. W.

    1980-01-01

    The overall objective of this program is to define an advanced converter system employing 1980's technology in all subsystem and component areas for use in electrochemical energy storage systems. Additional experimental effort will validate elements of the advanced commutation circuitry on a full-scale breadboard basis. Improved models of battery electrical characteristics are beng defined and experimental apparatus is being designed to measure these characteristics and to enable better definition of the battery-power conditioner interface. Improvement of energy-storage system performance through modification of battery converter characteristics will also be investigated. During this first year of the contract, a new more advanced concept for power conditioning based on a concept defined by United Technologies Corporation for fuel cell use was evaluated. This high switching frequency concept has the potential for significantly reducing the size and cost of battery plant power conditioners. As a result, the Department of Energy authorized redirection of the program to first evaluate this new concept and then to reorient the program to adopt this concept as the primary one. Progress is reported. (WHK)

  7. Genetic Association of Interleukin-31 Gene Polymorphisms with Epithelial Ovarian Cancer in Chinese Population

    Directory of Open Access Journals (Sweden)

    Chenlu Liu

    2018-01-01

    Full Text Available Roles of interleukin-31 (IL-31 in the development and progression of human epithelial ovarian cancer are largely unknown. Studies report that the polymorphisms, rs7977932 C>G and rs4758680 C>A in IL-31, affect the expression level of IL-31. In the present study, we examined 412 patients with epithelial ovarian cancer and 428 healthy individuals to explore whether these polymorphisms are associated with the epithelial ovarian cancer in Chinese women. The genotype of the polymorphisms in each individual was identified. The associations of the polymorphisms with patients’ clinical characteristics and outcomes were evaluated. For rs7977932, the frequency of the CG/GG was significantly decreased in patients with epithelial ovarian cancer. However, the frequency of the rs4758680 CA/AA was significantly increased in those patients. Moreover, the frequency of rs7977932 CG/GG genotype was significantly higher in patients with less advanced FIGO stages. Kaplan-Meier curve showed that patients with CG/GG genotypes of rs7977932 had a decreased risk for recurrence compared to those with CC genotype. Our findings suggested that rs7977932 and rs4758680 of IL-31 may be associated with the development and progression of the epithelial ovarian cancer in the Chinese population. IL-31, therefore, may be a potential therapeutic target for the development of drugs to treat the disease.

  8. Introduction of staging laparoscopy in the management of advanced epithelial ovarian, tubal and peritoneal cancer: impact on prognosis in a single institution experience.

    Science.gov (United States)

    Fagotti, A; Vizzielli, G; Fanfani, F; Costantini, B; Ferrandina, G; Gallotta, V; Gueli Alletti, S; Tortorella, L; Scambia, G

    2013-11-01

    To evaluate the prognostic impact of routinely use of staging laparoscopy (S-LPS) in patients with primary advanced epithelial ovarian cancer (AEOC). All women were submitted to S-LPS before receiving primary debulking surgery (PDS) or neoadjuvant treatment (NACT). The surgical and survival outcome were evaluated by univariate and multivariate analysis. Among 300 consecutive patients submitted to S-LPS no complications related to the surgical procedure were registered. The laparoscopic evaluation showed that almost half of the patients (46.3%) had a high tumor load. One-hundred forty-eight (49.3%) women were considered suitable for PDS and the remaining 152 (50.7%) were submitted to NACT. The percentages of complete (residual tumor, RT=0) and optimal (RTperformance status (p=0.016) maintained an independent association with the PFS. Including S-LPS in a tertiary referral center for the management AEOC does not appear to have a negative impact in terms of survival and it may be helpful to individualize the treatment avoiding unnecessary laparotomies and surgical complications. © 2013.

  9. Advanced Turbine Systems (ATS) program conceptual design and product development. Quarterly progress report, December 1, 1995--February 29, 1996

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-06-01

    This report describes the overall program status of the General Electric Advanced Gas Turbine Development program, and reports progress on three main task areas. The program is focused on two specific products: (1) a 70-MW class industrial gas turbine based on the GE90 core technology, utilizing a new air cooling methodology; and (2) a 200-MW class utility gas turbine based on an advanced GE heavy-duty machine, utilizing advanced cooling and enhancement in component efficiency. The emphasis for the industrial system is placed on cycle design and low emission combustion. For the utility system, the focus is on developing a technology base for advanced turbine cooling while achieving low emission combustion. The three tasks included in this progress report are on: conversion to a coal-fueled advanced turbine system, integrated program plan, and design and test of critical components. 13 figs., 1 tab.

  10. ARCHER Project: Progress on Material and component activities for the Advanced High Temperature Reactor

    International Nuclear Information System (INIS)

    Buckthorpe, D.E.

    2014-01-01

    The ARCHER (Advanced High-Temperature Reactors for Cogeneration of Heat and Electricity R&D) integrated project is a four year project which was started in 2011 as part of the European Commission 7th Framework Programme (FP7) to perform High Temperature Reactor technology R&D in support of reactor demonstration. The project consortium encompasses conventional and Nuclear Industry, Utilities, Technical Support Organizations, Research & Development Organizations and Academia. The activities involved contribute to the Generation IV (GIF) International Forum and collaborate with related projects in the US, China, Japan, and the Republic of Korea in cooperation with IAEA and ISTC. This paper addresses the progress of the work on ARCHER materials and component activities since the start of the project and underlines some of the main conclusions reached. (author)

  11. Prognostic factors for progression-free and overall survival in advanced biliary tract cancer

    DEFF Research Database (Denmark)

    Bridgewater, J; Lopes, A; Wasan, H

    2016-01-01

    independently with outcome. This score was validated externally by receiver operating curve (ROC) analysis using the independent international dataset. RESULTS: A total of 410 patients were included from the ABC-02 study and 753 from the international dataset. An overall survival (OS) and progression......BACKGROUND: Biliary tract cancer is an uncommon cancer with a poor outcome. We assembled data from the National Cancer Research Institute (UK) ABC-02 study and 10 international studies to determine prognostic outcome characteristics for patients with advanced disease. METHODS: Multivariable...... biliary tract cancer derived from the ABC-02 study that are validated in an international dataset. Although these findings establish the benchmark for the prognostic evaluation of patients with ABC and confirm the value of longheld clinical observations, the ability of the model to correctly predict...

  12. Material and component progress within ARCHER for advanced high temperature reactor

    International Nuclear Information System (INIS)

    Buckthorpe, D.E.; Davies, M.; Pra, F.; Bonnamy, P.; Fokkens, J.; Heijna, M.; Bout, N. de; Vreeling, A.; Bourlier, F.; Lhachemi, D.; Woayehune, A.; Dubiez-le-Goff, S.; Hahner, P.; Futterer, M.; Berka, J.; Kalivodora, J.; Pouchon, M.A.; Schmitt, R.; Homerin, P.; Marsden, B.; Mummery, P.; Mutch, G.; Ponca, D.; Buhl, P.; Hoffmann, M.; Rondet, F.; Pecherty, A.; Baurand, F.; Alenda, F.; Esch, M.; Kohlz, N.; Reed, J.; Fachinger, J.; Klower, Dr.

    2014-01-01

    The ARCHER (Advanced High-Temperature Reactors for Cogeneration of Heat and Electricity R and D) integrated project started in 2011 as part of the European Commission 7. Framework Programme (FP7) for a period of four years to perform High Temperature Reactor technology R and D in support of reactor demonstration. The project consortium encompasses conventional and Nuclear Industry, Utilities, Technical Support Organizations, Research and Development Organizations and Academia. The activities involved contribute to the Generation IV (GIF) International Forum and collaborate with related projects in the US, China, Japan, and the Republic of Korea in cooperation with IAEA and ISTC. This paper addresses the progress of the work on materials and component technologies within ARCHER over the first two years of the project. (authors)

  13. The receptor for advanced glycation end products (RAGE contributes to the progression of emphysema in mice.

    Directory of Open Access Journals (Sweden)

    Nisha Sambamurthy

    Full Text Available Several recent clinical studies have implied a role for the receptor for advanced glycation end products (RAGE and its variants in chronic obstructive pulmonary disease (COPD. In this study we have defined a role for RAGE in the pathogenesis of emphysema in mice. RAGE deficient mice (RAGE-/- exposed to chronic cigarette smoke were significantly protected from smoke induced emphysema as determined by airspace enlargement and had no significant reduction in lung tissue elastance when compared to their air exposed controls contrary to their wild type littermates. The progression of emphysema has been largely attributed to an increased inflammatory cell-mediated elastolysis. Acute cigarette smoke exposure in RAGE-/- mice revealed an impaired early recruitment of neutrophils, approximately a 6-fold decrease compared to wild type mice. Hence, impaired neutrophil recruitment with continued cigarette smoke exposure reduces elastolysis and consequent emphysema.

  14. Radioummunoassay of steroids in serum and ovarian fluid during egg overripening in goldfish

    International Nuclear Information System (INIS)

    Formacion, M.J.; Venkatesh, B.; Tan, C.H.; Lam, T.J.

    1996-01-01

    Changes in steroid hormone levels in the serum and ovarian fluid during egg overripening in goldfish were studied by radioimmunoassay (RIA). Ovulated eggs retained in the ovarian cavity became overripe at around 12h after ovulation based on loss of fertilizability with advanced degeneration by 24 hour. Blood and ovarian fluid (OF) were obtained at 0, 3, 6, 12, 187 and 24h after ovulation. Prior to RIA, serum steroids were extracted directly with redistilled diethyl ether. Because of limited availability, steroids were separated from the ovarian fluid by reverse phase high performance liquid chromatography (HPLC). Both serum and ovarian fluid progesterone (P) showed a highly significant decline at 18h with a further decline at 24h. In the ovarian fluid, P levels were higher than in the serum. Serum 17 α, 20B-dihydroxy-4-pregnen-3-one (17,20B-P) levels showed a progressive and more rapid decline, decreasing significantly at 12h with further decreases by 18h and 24h. Serum testosterone (T) increased significantly at 3h, remained high till 18h, and declined thereafter to the 0h level. for estradiol-17B (E 2 , levels there were no significant changes observed in the serum fluid, there were no significant difference between 6 and 24h. In the ovarian fluid, there were no significant changes in E 2 , T or 17,20B-P levels. The time course of changes in the levels of steroids in the serum and ovarian fluid (OF) did not strictly coincide with that of overripening based on egg viability. (author)

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

    National Research Council Canada - National Science Library

    Curtin, John P

    2003-01-01

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

  16. Volume-based quantitative FDG PET/CT metrics and their association with optimal debulking and progression-free survival in patients with recurrent ovarian cancer undergoing secondary cytoreductive surgery

    Energy Technology Data Exchange (ETDEWEB)

    Vargas, H.A.; Burger, I.A.; Micco, M.; Sosa, R.E.; Weber, W.; Hricak, H.; Sala, E. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Goldman, D.A. [Memorial Sloan Kettering Cancer Center, Department of Epidemiology and Biostatistics, New York, NY (United States); Chi, D.S. [Memorial Sloan Kettering Cancer Center, Department of Surgery, New York, NY (United States)

    2015-11-15

    Our aim was to evaluate the associations between quantitative {sup 18}F-fluorodeoxyglucose positron-emission tomography (FDG-PET) uptake metrics, optimal debulking (OD) and progression-free survival (PFS) in patients with recurrent ovarian cancer undergoing secondary cytoreductive surgery. Fifty-five patients with recurrent ovarian cancer underwent FDG-PET/CT within 90 days prior to surgery. Standardized uptake values (SUV{sub max}), metabolically active tumour volumes (MTV), and total lesion glycolysis (TLG) were measured on PET. Exact logistic regression, Kaplan-Meier curves and the log-rank test were used to assess associations between imaging metrics, OD and PFS. MTV (p = 0.0025) and TLG (p = 0.0043) were associated with OD; however, there was no significant association between SUV{sub max} and debulking status (p = 0.83). Patients with an MTV above 7.52 mL and/or a TLG above 35.94 g had significantly shorter PFS (p = 0.0191 for MTV and p = 0.0069 for TLG). SUV{sub max} was not significantly related to PFS (p = 0.10). PFS estimates at 3.5 years after surgery were 0.42 for patients with an MTV ≤ 7.52 mL and 0.19 for patients with an MTV > 7.52 mL; 0.46 for patients with a TLG ≤ 35.94 g and 0.15 for patients with a TLG > 35.94 g. FDG-PET metrics that reflect metabolic tumour burden are associated with optimal secondary cytoreductive surgery and progression-free survival in patients with recurrent ovarian cancer. (orig.)

  17. Volume-based quantitative FDG PET/CT metrics and their association with optimal debulking and progression-free survival in patients with recurrent ovarian cancer undergoing secondary cytoreductive surgery

    International Nuclear Information System (INIS)

    Vargas, H.A.; Burger, I.A.; Micco, M.; Sosa, R.E.; Weber, W.; Hricak, H.; Sala, E.; Goldman, D.A.; Chi, D.S.

    2015-01-01

    Our aim was to evaluate the associations between quantitative 18 F-fluorodeoxyglucose positron-emission tomography (FDG-PET) uptake metrics, optimal debulking (OD) and progression-free survival (PFS) in patients with recurrent ovarian cancer undergoing secondary cytoreductive surgery. Fifty-five patients with recurrent ovarian cancer underwent FDG-PET/CT within 90 days prior to surgery. Standardized uptake values (SUV max ), metabolically active tumour volumes (MTV), and total lesion glycolysis (TLG) were measured on PET. Exact logistic regression, Kaplan-Meier curves and the log-rank test were used to assess associations between imaging metrics, OD and PFS. MTV (p = 0.0025) and TLG (p = 0.0043) were associated with OD; however, there was no significant association between SUV max and debulking status (p = 0.83). Patients with an MTV above 7.52 mL and/or a TLG above 35.94 g had significantly shorter PFS (p = 0.0191 for MTV and p = 0.0069 for TLG). SUV max was not significantly related to PFS (p = 0.10). PFS estimates at 3.5 years after surgery were 0.42 for patients with an MTV ≤ 7.52 mL and 0.19 for patients with an MTV > 7.52 mL; 0.46 for patients with a TLG ≤ 35.94 g and 0.15 for patients with a TLG > 35.94 g. FDG-PET metrics that reflect metabolic tumour burden are associated with optimal secondary cytoreductive surgery and progression-free survival in patients with recurrent ovarian cancer. (orig.)

  18. Experimental research progress on passive safety systems of Chinese advanced PWR

    International Nuclear Information System (INIS)

    Xiao Zejun; Zhuo Wenbin; Zheng Hua; Chen Bingde; Zong Guifang; Jia Dounan

    2003-01-01

    TMI and Chernobyl accidents, having pronounced impact on nuclear industries, triggered the governments as well as interested institutions to devote much attention to the safety of nuclear power plant and public's requirements on nuclear power plant safety were also going to be stricter and stricter. It is obvious that safety level of an ordinary light water reactor is no longer satisfactory to these requirements. Recently, the safety authorities have recommended the implementation of passive system to improve the safety of nuclear reactors. Passive safety system is one of the main differences between Chinese advanced PWR and other conventional PWR. The working principle of passive safety system is to utilize the gravity, natural convection (natural circulation) and stored energy to implement the system's safety function. Reactors with passive safety systems are not only safer, but also more economical. The passive safety system of Chinese advanced PWR is composed of three independent systems, i.e. passive containment cooling system, passive residual heat removal system and passive core makeup tank injection system. This paper is a summary of experimental research progress on passive containment cooling system, passive residual heat removal system and passive core makeup tank injection system

  19. IP Chemo for Ovarian Cancer is Underused

    Science.gov (United States)

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

  20. Diet and Physical Activity Change or Usual Care in Improving Progression-Free Survival in Patients With Previously Treated Stage II, III, or IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

    Science.gov (United States)

    2018-02-14

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

  1. Novel paradigm for immunotherapy of ovarian cancer by engaging prophylactic immunity against hepatitis B virus.

    Science.gov (United States)

    Malecki, Marek; Putzer, Emily; Quach, Caroline; Dodivenaka, Chaitanya; Tombokan, Xenia

    2016-12-01

    Only eight women out of one hundred diagnosed with ovarian epithelial cancers, which progressed to the clinical stage IV, survive 10 years. First line therapies: surgery, chemotherapy, and radiation therapy inflict very serious iatrogenic consequences. Passive immunotherapy of ovarian cancers offers only low efficacy. Prophylactic and therapeutic vaccines for ovarian cancers are not available. Interestingly, prophylactic vaccines for Hepatitis B Viruses (HBV) are very effective. The specific aim of this work was to design, synthesize, and administer biomolecules, which would engage prophylactic, vaccination-induced immunity for HBV towards killing of ovarian cancer cells with high specificity and efficacy. Tissue biopsies, ascites, and blood were acquired from the patients, whose identities were entirely concealed in accordance with the Declaration of Helsinki, pursuant to the Institutional Review Board approval, and with the Patients' informed consent. By biomolecular engineering, we have created a novel family of biomolecules: antibody × vaccine engineered constructs (AVEC: anti-HER-2 × HBsAg). We have collected the blood from the volunteers, and measured the titers of anti-HBV antibodies resulting from the FDA approved and CDC scheduled HBV vaccinations. We have acquired tumor biopsies, ascites, and blood from patients suffering from the advanced ovarian cancers. We have established cultures of HER-2 over-expressing epithelial ovarian cancers: OV-90, TOC-112D, SKOV-3, as well as human ovary surface epithelial (HOSE) and human artery endothelial (HAE) cells. Treatment of the HER-2+ ovarian cancer cells with AVEC: anti-HER-2 × HBsAg, accompanied by administration of blood drawn from patients with high titers of the anti-HBV antibodies, resulted in much higher therapeutic efficacy as compared to treatment with the naked anti-HER-2 antibodies alone and/or with the relevant isotype antibodies. This treatment had practically no effect upon the HOSE and HAE

  2. Quality of life is significantly associated with survival in women with advanced epithelial ovarian cancer: An ancillary data analysis of the NRG Oncology/Gynecologic Oncology Group (GOG-0218) study.

    Science.gov (United States)

    Phippen, N T; Secord, A A; Wolf, S; Samsa, G; Davidson, B; Abernethy, A P; Cella, D; Havrilesky, L J; Burger, R A; Monk, B J; Leath, C A

    2017-10-01

    Evaluate association between baseline quality of life (QOL) and changes in QOL measured by FACT-O TOI with progression-free disease (PFS) and overall survival (OS) in advanced epithelial ovarian cancer (EOC). Patients enrolled in GOG-0218 with completed FACT-O TOI assessments at baseline and at least one follow-up assessment were eligible. Baseline FACT-O TOI scores were sorted by quartiles (Q1-4) and outcomes compared between Q1 and Q2-4 with log-rank statistic and multivariate Cox regression adjusting for age, stage, post-surgical residual disease size, and performance status (PS). Trends in FACT-O TOI scores from baseline to the latest follow-up assessment were evaluated for impact on intragroup (Q1 or Q2-4) outcome by log-rank analysis. Of 1152 eligible patients, 283 formed Q1 and 869 formed Q2-4. Mean baseline FACT-O TOI scores were 47.5 for Q1 vs. 74.7 for Q2-4 (P<0.001). Q1 compared to Q2-4 had worse median OS (37.5 vs. 45.6months, P=0.001) and worse median PFS (12.5 vs. 13.1months, P=0.096). Q2-4 patients had decreased risks of disease progression (HR 0.974, 95% CI 0.953-0.995, P=0.018), and death (HR 0.963, 95% CI 0.939-0.987, P=0.003) for each five-point increase in baseline FACT-O TOI. Improving versus worsening trends in FACT-O TOI scores were associated with longer median PFS (Q1: 12.7 vs. 8.6months, P=0.001; Q2-4: 16.7 vs. 11.1months, P<0.001) and median OS (Q1: 40.8 vs. 16months, P<0.001; Q2-4: 54.4 vs. 33.6months, P<0.001). Baseline FACT-O TOI scores were independently prognostic of PFS and OS while improving compared to worsening QOL was associated with significantly better PFS and OS in women with EOC. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Prognostic role of mesenteric lymph nodes involvement in patients undergoing posterior pelvic exenteration during radical or supra-radical surgery for advanced ovarian cancer.

    Science.gov (United States)

    Berretta, Roberto; Capozzi, Vito Andrea; Sozzi, Giulio; Volpi, Lavinia; Ceni, Valentina; Melpignano, Mauro; Giordano, Giovanna; Marchesi, Federico; Monica, Michela; Di Serio, Maurizio; Riccò, Matteo; Ceccaroni, Marcello

    2018-04-01

    The aim of this retrospective study is to analyze the prognostic role and the practical implication of mesenteric lymph nodes (MLN) involvements in advanced ovarian cancer (AOC). A total of 429 patients with AOC underwent surgery between December 2007 and May 2017. We included in the study 83 patients who had primary (PDS) or interval debulking surgery (IDS) for AOC with bowel resection. Numbers, characteristics and surgical implication of MLN involvement were considered. Eighty-three patients were submitted to bowel resection during cytoreduction for AOC. Sixty-seven patients (80.7%) underwent primary debulking surgery (PDS). Sixteen patients (19.3%) experienced interval debulking surgery (IDS). 43 cases (51.8%) showed MLN involvement. A statistic correlation between positive MLN and pelvic lymph nodes (PLN) (p = 0.084), aortic lymph nodes (ALN) (p = 0.008) and bowel infiltration deeper than serosa (p = 0.043) was found. A longer overall survival (OS) and disease-free survival was observed in case of negative MLN in the first 20 months of follow-up. No statistical differences between positive and negative MLN in terms of operative complication, morbidity, Ca-125, type of surgery (radical vs supra-radical), length and site of bowel resection, residual disease and site of recurrence were observed. An important correlation between positive MLN, ALN and PLN was detected; these results suggest a lymphatic spread of epithelial AOC similar to that of primary bowel cancer. The absence of residual disease after surgery is an independent prognostic factor; to achieve this result should be recommended a radical bowel resection during debulking surgery for AOC with bowel involvement.

  4. The Advanced Glaucoma Intervention Study (AGIS): 14. Distinguishing progression of glaucoma from visual field fluctuations.

    Science.gov (United States)

    Kim, Jonghyeon; Dally, Leonard G; Ederer, Fred; Gaasterland, Douglas E; VanVeldhuisen, Paul C; Blackwell, Beth; Sullivan, E Kenneth; Prum, Bruce; Shafranov, George; Beck, Allen; Spaeth, George L

    2004-11-01

    To determine the least worsening of a visual field (VF) and the least number of confirming tests needed to identify progression of glaucomatous VF defects. Cohort study of participants in a clinical trial. Seven hundred fifty-two eyes of 565 patients with advanced glaucoma. Visual field tests were quantified with the Advanced Glaucoma Intervention Study (AGIS) VF defect score and the Humphrey Field Analyzer mean deviation (MD). Follow-up was 8 to 13 years. Two measures based on the AGIS VF defect score: (1) sustained decrease of VF (SDVF), a worsening from baseline by 2 (alternatively, 3 or 4) or more units and sustained for 2 (alternatively, 3) consecutive 6-month visits and (2) after the occurrence of SDVF, the average percent of eyes with worsening by 2 (alternatively, 3 or 4) or more units from baseline. Two similar measures based on MD. Based on the original AGIS criteria for SDVF (a worsening of 4 units in the AGIS score sustained during 3 consecutive 6-month visits), 31% of eyes had an SDVF. The percent of eyes with a sustained event increases by approximately 10% when either the minimum number of units of field loss or the minimum number of 6-month visits during which the loss is sustained decreases by 1. During 3 years of follow-up after a sustained event, a worsening of at least 2 units was found in 72% of eyes that had a 2-visit sustained event. The same worsening was found in 84% of eyes that had a 3-visit sustained event. Through the next 10 years after a sustained event, based on worsening of 2, 3, or 4 units at 2 or 3 consecutive tests, the loss reoccurred, on average, in >/=75% of study eyes. Results for MD are similar. In patients with advanced glaucoma, a single confirmatory test 6 months after a VF worsening indicates with at least 72% probability a persistent defect when the worsening is defined by at least 2 units of AGIS score or by at least 2 decibels of MD. When the number of confirmatory tests is increased from 1 to 2, the percentage of

  5. E2F5 status significantly improves malignancy diagnosis of epithelial ovarian cancer

    KAUST Repository

    Kothandaraman, Narasimhan; Bajic, Vladimir B.; Brendan, Pang NK; Huak, Chan Y; Keow, Peh B; Razvi, Khalil; Salto-Tellez, Manuel; Choolani, Mahesh

    2010-01-01

    Background: Ovarian epithelial cancer (OEC) usually presents in the later stages of the disease. Factors, especially those associated with cell-cycle genes, affecting the genesis and tumour progression for ovarian cancer are largely unknown. We

  6. An Update on Ovarian Aging and Ovarian Reserve Tests

    Directory of Open Access Journals (Sweden)

    Migraci Tosun

    2016-12-01

    Full Text Available Ovaries are the female organs that age more quickly than other tissues such as the uterus, the pituitary gland or pancreas. Different from males, an interesting question is why and how the females lose fertility so rapidly. During the aging process, both the number and quality of the oocytes in the ovaries decrease and reach to a point beyond that no more viable offspring may be produced and the associated cyclic endocrinological activities cease, entering the menopause in females at an average age of 50 years. Females who delayed childbearing with or without their willing until their 30 years or 40 years constitute the largest portion of the total infertility population. Ovarian reserve tests (ORTs provide an indirect estimate of a female�s diminishing ovarian reserve or remaining follicular pool. This article briefly reviews recent progresses in relation to ovarian aging and ORTs.

  7. Progress making the top end optical assembly (TEOA) for the 4-meter Advanced Technology Solar Telescope

    Science.gov (United States)

    Canzian, Blaise; Barentine, J.; Arendt, J.; Bader, S.; Danyo, G.; Heller, C.

    2012-09-01

    L-3 Integrated Optical Systems (IOS) Division has been selected by the National Solar Observatory (NSO) to design and produce the Top End Optical Assembly (TEOA) for the 4-meter Advanced Technology Solar Telescope (ATST) to operate at Haleakal', Maui. ATST will perform to a very high optical performance level in a difficult thermal environment. The TEOA, containing the 0.65-meter silicon carbide secondary mirror and support, mirror thermal management system, mirror positioning and fast tip-tilt system, field stop with thermally managed heat dump, thermally managed Lyot stop, safety interlock and control system, and support frame, operates in the "hot spot" at the prime focus of the ATST and so presents special challenges. In this paper, we describe progress in the L-3 technical approach to meeting these challenges, including silicon carbide off-axis mirror design, fabrication, and high accuracy figuring and polishing all within L-3; mirror support design; the design for stray light control; subsystems for opto-mechanical positioning and high accuracy absolute mirror orientation sensing; Lyot stop design; and thermal management of all design elements to remain close to ambient temperature despite the imposed solar irradiance load.

  8. Recent Progress in Self-Supported Metal Oxide Nanoarray Electrodes for Advanced Lithium-Ion Batteries.

    Science.gov (United States)

    Zhang, Feng; Qi, Limin

    2016-09-01

    The rational design and fabrication of electrode materials with desirable architectures and optimized properties has been demonstrated to be an effective approach towards high-performance lithium-ion batteries (LIBs). Although nanostructured metal oxide electrodes with high specific capacity have been regarded as the most promising alternatives for replacing commercial electrodes in LIBs, their further developments are still faced with several challenges such as poor cycling stability and unsatisfying rate performance. As a new class of binder-free electrodes for LIBs, self-supported metal oxide nanoarray electrodes have many advantageous features in terms of high specific surface area, fast electron transport, improved charge transfer efficiency, and free space for alleviating volume expansion and preventing severe aggregation, holding great potential to solve the mentioned problems. This review highlights the recent progress in the utilization of self-supported metal oxide nanoarrays grown on 2D planar and 3D porous substrates, such as 1D and 2D nanostructure arrays, hierarchical nanostructure arrays, and heterostructured nanoarrays, as anodes and cathodes for advanced LIBs. Furthermore, the potential applications of these binder-free nanoarray electrodes for practical LIBs in full-cell configuration are outlined. Finally, the future prospects of these self-supported nanoarray electrodes are discussed.

  9. Standardization of advanced light water reactors and progress on achieving utility requirements

    International Nuclear Information System (INIS)

    Marston, T.U.; Layman, W.H.; Bockhold, G. Jr.

    1992-01-01

    This paper reports that for a number of years, the U.S. utilities had led an industry-wide effort to establish a technical foundation for the design of the next generation of light water reactors in the United States. Since 1985, this utility initiative has been effected through a major technical program managed by the Electric Power Research Institute (EPRI); the U.S. Advanced Light Water Reactor (ALWR) Program. In addition to the U.S. utility leadership and sponsorship, the ALWR Program also has the participation and sponsorship of a number of international utility companies and close cooperation with the U.S. Department of Energy (DOE). The NPOC Strategic Plan for Building New Nuclear Plants creates a framework within which new standardized nuclear plants may be built. The Strategic Plan is an expression of the nuclear energy industry's serious intent to create the necessary conditions for new plant construction and operation. The industry has assembled a comprehensive, integrated list of actions that must be taken before new plants will be built and assigns responsibility for managing the various issues and sets time-tables and milestones against which we must measure progress

  10. Distinct neural substrates of visuospatial and verbal-analytic reasoning as assessed by Raven's Advanced Progressive Matrices

    NARCIS (Netherlands)

    Chen, Zhencai; De Beuckelaer, A.; Wang, Xu; Liu, Jia

    2017-01-01

    Recent studies revealed spontaneous neural activity to be associated with fluid intelligence (gF) which is commonly assessed by Raven’s Advanced Progressive Matrices, and embeds two types of reasoning: visuospatial and verbal-analytic reasoning. With resting-state fMRI data, using global brain

  11. Current status and future prospects of hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) clinical trials in ovarian cancer.

    Science.gov (United States)

    Cowan, Renee A; O'Cearbhaill, Roisin E; Zivanovic, Oliver; Chi, Dennis S

    2017-08-01

    The natural history of advanced-stage epithelial ovarian cancer is one of clinical remission after surgery and platinum/taxane-based intravenous (IV) and/or intraperitoneal (IP) chemotherapy followed by early or late recurrence in the majority of patients. Prevention of progression and recurrence remains a major hurdle in the management of ovarian cancer. Recently, many investigators have evaluated the use of normothermic and hyperthermic intraoperative IP drug delivery as a management strategy. This is a narrative review of the current status of clinical trials of hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) in ovarian cancer and the future directions for this treatment strategy. The existing studies on HIPEC in patients with epithelial ovarian cancer are mostly retrospective in nature, are heterogeneous with regards to combined inclusion of primary and recurrent disease and lack unbiased data. Until data are available from evidence-based trials, it is reasonable to conclude that surgical cytoreduction and HIPEC is a rational and interesting, though still investigative, approach in the management of epithelial ovarian cancer, whose use should be employed within prospective clinical trials.

  12. Retinopathy of prematurity: mutations in the Norrie disease gene and the risk of progression to advanced stages.

    Science.gov (United States)

    Haider, M Z; Devarajan, L V; Al-Essa, M; Srivastva, B S; Kumar, H; Azad, R; Rashwan, N

    2001-04-01

    Retinopathy of prematurity (ROP) is a retinal vascular disease that occurs in infants with short gestational age and low birth weight and may lead to retinal detachment and blindness. Missense mutations in the Norrie disease (ND) gene have been associated with the risk of progression to advanced stages in cases of ROP from the US and also in clinically similar ND and familial exudative vitreoretinopathy. We have screened two ND gene mutations, namely A105T and Val60Glu, by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and allele-specific PCR methods, respectively, in 210 Kuwaiti premature newborns to replicate these findings in a different ethnic group. In the Kuwaiti premature newborn cohort, 115 of 210 babies had no eye problems and served as controls, while 95 were cases of ROP. In 71 of 95 ROP cases, the disease regressed spontaneously on or before stage 3, while in 24 of 95 ROP cases the disease progressed to advanced stages 4 and 5. In case of missense mutation (A105T), the AA genotype was detected in 96% of controls compared with 87% of ROP cases (NS); similarly no significant difference was found between spontaneously regressed ROP cases and those who progressed to advanced stages. For the Val60Glu mutation, no significant association was detected between the genotype and progression of ROP to advanced stages. Unlike data from the US, our findings from a Kuwaiti cohort of ROP cases and controls suggest a lack of association between the two ND gene mutations (A105T and Val60Glu) and ROP and the risk of progression of the disease to advanced stages.

  13. Targeted Therapies in Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Jurjees Hasan

    2010-02-01

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

  14. Targeted Therapies in Epithelial Ovarian Cancer

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-02-23

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

  15. Ovarian Autoantibodies Predict Ovarian Cancer

    Science.gov (United States)

    2010-11-01

    Expression of thymidine 459 phosphorylase in epithelial ovarian cancer: correlation with angiogenesis, apoptosis , and 460 ultrasound-derived peak...trafficking, activation of S1P1 can promote or inhibit apoptosis of 41 immune cells depending on the balance of cytokines [7]. Knockout of S1P1 (LP(B1...EDG-1) in 42 mice is embryologically lethal [8]. S1P1 also has a role in inflammatory disease such as graft 43 versus host disease and multiple

  16. Treatment Beyond Progression in Patients with Advanced Renal Cell Carcinoma Treated with Nivolumab in CheckMate 025

    DEFF Research Database (Denmark)

    Escudier, Bernard; Motzer, Robert J; Sharma, Padmanee

    2017-01-01

    BACKGROUND: Response patterns to nivolumab differ from those seen with other approved targeted therapies. OBJECTIVE: To investigate the efficacy of nivolumab in previously treated patients with advanced renal cell carcinoma who were treated beyond (Response Evaluation Criteria In Solid Tumors......) RECIST progression. DESIGN, SETTING, AND PARTICIPANTS: This was a subgroup analysis of patients treated with nivolumab in the phase 3 CheckMate 025 study. Patients continuing to tolerate therapy and exhibiting investigator-assessed clinical benefit were eligible to be treated beyond RECIST progression...... (TBP) and received therapy for ≥4 wk after first progression; patients not treated beyond RECIST progression (NTBP) received 0 wk to Nivolumab 3mg/kg intravenously every 2 wk. RESULTS AND LIMITATIONS: Of 406 nivolumab-treated patients, 316 (78...

  17. The Role & Action of Prohibition, an Antiproliferative Gene, in Ovarian Cancer

    National Research Council Canada - National Science Library

    Thompson, Winston E

    2007-01-01

    ... expression pattern of prohibitin in normal ovary, ovarian tumors of patients with early (FIGO stage 1) and advanced (FIGO stage II-IV) stages of ovarian cancer, using immunohistochemistry, in situ hybridization, Western and Northern blot analyses...

  18. Ovarian hormones and obesity.

    Science.gov (United States)

    Leeners, Brigitte; Geary, Nori; Tobler, Philippe N; Asarian, Lori

    2017-05-01

    Obesity is caused by an imbalance between energy intake, i.e. eating and energy expenditure (EE). Severe obesity is more prevalent in women than men worldwide, and obesity pathophysiology and the resultant obesity-related disease risks differ in women and men. The underlying mechanisms are largely unknown. Pre-clinical and clinical research indicate that ovarian hormones may play a major role. We systematically reviewed the clinical and pre-clinical literature on the effects of ovarian hormones on the physiology of adipose tissue (AT) and the regulation of AT mass by energy intake and EE. Articles in English indexed in PubMed through January 2016 were searched using keywords related to: (i) reproductive hormones, (ii) weight regulation and (iii) central nervous system. We sought to identify emerging research foci with clinical translational potential rather than to provide a comprehensive review. We find that estrogens play a leading role in the causes and consequences of female obesity. With respect to adiposity, estrogens synergize with AT genes to increase gluteofemoral subcutaneous AT mass and decrease central AT mass in reproductive-age women, which leads to protective cardiometabolic effects. Loss of estrogens after menopause, independent of aging, increases total AT mass and decreases lean body mass, so that there is little net effect on body weight. Menopause also partially reverses women's protective AT distribution. These effects can be counteracted by estrogen treatment. With respect to eating, increasing estrogen levels progressively decrease eating during the follicular and peri-ovulatory phases of the menstrual cycle. Progestin levels are associated with eating during the luteal phase, but there does not appear to be a causal relationship. Progestins may increase binge eating and eating stimulated by negative emotional states during the luteal phase. Pre-clinical research indicates that one mechanism for the pre-ovulatory decrease in eating is a

  19. 60 years of advances in neuropsychopharmacology for improving brain health, renewed hope for progress.

    Science.gov (United States)

    Millan, Mark J; Goodwin, Guy M; Meyer-Lindenberg, Andreas; Ögren, Sven Ove

    2015-05-01

    Pharmacotherapy is effective in helping many patients suffering from psychiatric and neurological disorders, and both psychotherapeutic and stimulation-based techniques likewise have important roles to play in their treatment. However, therapeutic progress has recently been slow. Future success for improving the control and prevention of brain disorders will depend upon deeper insights into their causes and pathophysiological substrates. It will also necessitate new and more rigorous methods for identifying, validating, developing and clinically deploying new treatments. A field of Research and Development (R and D) that remains critical to this endeavour is Neuropsychopharmacology which transformed the lives of patients by introducing pharmacological treatments for psychiatric disorder some 60 years ago. For about half of this time, the European College of Neuropsychopharmacology (ECNP) has fostered efforts to enhance our understanding of the brain, and to improve the management of psychiatric disorders. Further, together with partners in academia and industry, and in discussions with regulators and patients, the ECNP is implicated in new initiatives to achieve this goal. This is then an opportune moment to survey the field, to analyse what we have learned from the achievements and failures of the past, and to identify major challenges for the future. It is also important to highlight strategies that are being put in place in the quest for more effective treatment of brain disorders: from experimental research and drug discovery to clinical development and collaborative ventures for reinforcing "R and D". The present article sets the scene, then introduces and interlinks the eight articles that comprise this Special Volume of European Neuropsychopharmacology. A broad-based suite of themes is covered embracing: the past, present and future of "R and D" for psychiatric disorders; complementary contributions of genetics and epigenetics; efforts to improve the

  20. Progress on advanced tokamak and steady-state scenario development on DIII-D and NSTX

    Energy Technology Data Exchange (ETDEWEB)

    Doyle, E J [Department of Electrical Engineering and PSTI, University of California, Los Angeles, California 90095 (United States); Garofalo, A M [Columbia University, New York, New York 10027 (United States); Greenfield, C M [General Atomics, San Diego, California 92186-5608 (United States); Kaye, S M [Princeton Plasma Physics Laboratory, Princeton, New Jersey 08543-0451 (United States); Menard, J E [Princeton Plasma Physics Laboratory, Princeton, New Jersey 08543-0451 (United States); Murakami, M [Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831 (United States); Sabbagh, S A [Columbia University, New York, New York 10027 (United States); Austin, M E [University of Texas-Austin, Austin, Texas 78712 (United States); Bell, R E [Princeton Plasma Physics Laboratory, Princeton, New Jersey 08543-0451 (United States); Burrell, K H [General Atomics, San Diego, California 92186-5608 (United States); Ferron, J R [General Atomics, San Diego, California 92186-5608 (United States); Gates, D A [Princeton Plasma Physics Lab., Princeton, New Jersey 08543-0451 (United States); Groebner, R J; Hyatt, A W; Luce, T C; Petty, C C; Wade, M R; Waltz, R E [General Atomics, San Diego, California 92186-5608 (United States); Jayakumar, R J [Lawrence Livermore National Lab., Livermore, California 94550 (United States); Kinsey, J E [Lehigh Univ., Bethlehem, Pennsylvania 18015 (United States); LeBlanc, B P [Princeton Plasma Physics Lab., Princeton, New Jersey 08543-0451 (United States); McKee, G R [Univ. of Wisconsin-Madison, Madison, Wisconsin 53706 (United States); Okabayashi, M [Princeton Plasma Physics Lab., Princeton, New Jersey 08543-0451 (United States); Peng, Y-K M [Oak Ridge National Lab., Oak Ridge, Tennessee 37831 (United States); Politzer, P A [General Atomics, San Diego, California 92186-5608 (United States); Rhodes, T L [Dept. of Electrical Engineering and PSTI, Univ. of California, Los Angeles, California 90095 (United States)

    2006-12-15

    Advanced tokamak (AT) research seeks to develop steady-state operating scenarios for ITER and other future devices from a demonstrated scientific basis. Normalized target parameters for steady-state operation on ITER are 100% non-inductive current operation with a bootstrap current fraction f{sub BS} {>=} 60%, q{sub 95} {approx} 4-5 and G {identical_to}{beta}{sub N}H{sub scaling}/q{sub 95}{sup 2} {>=}0.3. Progress in realizing such plasmas is considered in terms of the development of plasma control capabilities and scientific understanding, leading to improved AT performance. NSTX has demonstrated active resistive wall mode stabilization with low, ITER-relevant, rotation rates below the critical value required for passive stabilization. On DIII-D, experimental observations and GYRO simulations indicate that ion internal transport barrier (ITB) formation at rational-q surfaces is due to equilibrium zonal flows generating high local E ? B shear levels. In addition, stability modelling for DIII-D indicates a path to operation at {beta}{sub N} {>=} 4 with q{sub min} {>=} 2, using broad, hollow current profiles to increase the ideal wall stability limit. Both NSTX and DIII-D have optimized plasma performance and expanded AT operational limits. NSTX now has long-pulse, high performance discharges meeting the normalized targets for an spherical torus-based component test facility. DIII-D has developed sustained discharges combining high beta and ITBs, with performance approaching levels required for AT reactor concepts, e.g. {beta}{sub N} = 4, H{sub 89} = 2.5, with f{sub BS} > 60%. Most importantly, DIII-D has developed ITER steady-state demonstration discharges, simultaneously meeting the targets for steady-state Q {>=} 5 operation on ITER set out above, substantially increasing confidence in ITER meeting its steady-state performance objective.

  1. Pretreatment advanced lung cancer inflammation index (ALI) for predicting early progression in nivolumab-treated patients with advanced non-small cell lung cancer.

    Science.gov (United States)

    Shiroyama, Takayuki; Suzuki, Hidekazu; Tamiya, Motohiro; Tamiya, Akihiro; Tanaka, Ayako; Okamoto, Norio; Nakahama, Kenji; Taniguchi, Yoshihiko; Isa, Shun-Ichi; Inoue, Takako; Imamura, Fumio; Atagi, Shinji; Hirashima, Tomonori

    2018-01-01

    Programmed death-ligand 1 (PD-L1) expression status is inadequate for indicating nivolumab in patients with non-small cell lung cancer (NSCLC). Because the baseline advanced lung cancer inflammation index (ALI) is reportedly associated with patient outcomes, we investigated whether the pretreatment ALI is prognostic in NSCLC patients treated with nivolumab. We retrospectively reviewed the medical records of all patients treated with nivolumab for advanced NSCLC between December 2015 and May 2016 at three Japanese institutes. Multivariate logistic regression and Cox proportional hazards models were used to assess the impact of the pretreatment ALI (and other inflammation-related parameters) on progression-free survival (PFS) and early progression (i.e., within 8 weeks after starting nivolumab). A total of 201 patients were analyzed; their median age was 68 years (range, 27-87 years), 67% were men, and 24% had an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or higher. An ECOG performance status ≥2, serum albumin ALI ALI ALI was found to be a significant independent predictor of early progression in patients with advanced NSCLC receiving nivolumab, and may help identify patients likely to benefit from continued nivolumab treatment in routine clinical practice. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  2. Ovarian maldescent

    Energy Technology Data Exchange (ETDEWEB)

    Trinidad, Carmen; Tardaguila, Francisco; Fernandez, Gabriel C.; Martinez, Concepcion; Chavarri, Elena; Rivas, Isabel [Departments of Radiology and Gynecology, Povisa Medical Center, Salamanca St. 5, 36211, Vigo (Pontevedra) (Spain)

    2004-05-01

    Undescended ovary is a rare disorder that can be associated with muellerian malformations. There is an unclear association with infertility and malignant disease. When an ovary is not in its normal location, it is sought in other locations above the pelvic brim. This is important in cases of undetermined cyclical abdominal pain, follicle aspiration and surgical castration. MRI has proven to be the best imaging method for finding an ovary in an anomalous position and for disregarding associated malformations. We report two patients with unilateral ovarian maldescent, one of them with Rokitansky-Kuester-Hauser syndrome. A review of the literature is included. (orig.)

  3. Exosomal DNMT1 mediates cisplatin resistance in ovarian cancer.

    Science.gov (United States)

    Cao, Ya-Lei; Zhuang, Ting; Xing, Bao-Heng; Li, Na; Li, Qin

    2017-08-01

    Ovarian cancer is the most common malignancy in women. Owing to late syndromic presentation and lack of efficient early detection, most cases are diagnosed at advanced stages. Surgery and platinum-based chemotherapy are still the standard care currently. However, resistance invoked often compromises the clinical value of the latter. Expression of DNA methyltransferase 1 (DNMT1) was analysed by gene array. Protein was determined by immunoblotting. Exosome was isolated with commercial kit. Cell proliferation was measured by CCK8 method. Annexin V-PI double staining was performed for apoptosis evaluation. Xenograft model was established and administrated with exosome. Tumour growth and overall survival were monitored. We demonstrated the upregulation of DNMT1 in both tumour and derived cell line. DNMT1 transcripts were highly enriched in exosomes from conditioned medium of ovarian cells. Co-incubation with exosomes stimulated endogenous expression and rendered host cell the resistance to cytotoxicity of cisplatin. In vivo administration of DNMT1-containing exosomes exacerbated xenograft progression and reduced overall survival significantly. Moreover, treatment with exosome inhibitor GW4869 almost completely restored sensitivity in resistant cells. Our data elucidated an unappreciated mechanism of exosomal DNMT1 in cisplatin resistance in ovarian cancer, also indicating the potential of the combination of exosome inhibitor with cisplatin in resistant patients. Copyright © 2017 John Wiley & Sons, Ltd.

  4. 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

  5. [Early detection of ovarian cancer: tomorrow? A review].

    Science.gov (United States)

    Chene, G; Penault-Llorca, F; Robin, N; Cayre, A; Provencher, D M; Dauplat, J

    2013-02-01

    Ovarian cancer is the most lethal of the gynaecological malignancies because this «silent killer» is almost always diagnosed at an advanced stage. Precursor lesions have at least been discovered. This review will describe in details specific features of tubal and ovarian preinvasive lesions and the old and novel techniques that could be used for early detection of ovarian cancer. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

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

    Science.gov (United States)

    Armstrong, Deborah K

    2017-11-01

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

  7. 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....

  8. Advances in materials science, Metals and Ceramics Division. Triannual progress report, October 1979-January 1980

    Energy Technology Data Exchange (ETDEWEB)

    1980-03-31

    Progress is summarized concerning magnetic fusion energy materials, laser fusion energy, aluminium-air battery and vehicle, geothermal research, oil-shale research, nuclear waste management, office of basic energy sciences research, and materials research notes. (FS)

  9. Nivolumab for Patients With Advanced Melanoma Treated Beyond Progression: Analysis of 2 Phase 3 Clinical Trials

    DEFF Research Database (Denmark)

    Long, Georgina V; Weber, Jeffrey S; Larkin, James

    2017-01-01

    IMPORTANCE: Immune checkpoint inhibitors have demonstrated atypical response patterns, which may not be fully captured by conventional response criteria. There is a need to better understand the potential benefit of continued immune checkpoint inhibition beyond progression. OBJECTIVE: To evaluate...

  10. Randomized phase II trial of carboplatin versus paclitaxel and carboplatin in platinum-sensitive recurrent advanced ovarian carcinoma: a GEICO (Grupo Espanol de Investigacion en Cancer de Ovario) study.

    Science.gov (United States)

    González-Martín, A J; Calvo, E; Bover, I; Rubio, M J; Arcusa, A; Casado, A; Ojeda, B; Balañá, C; Martínez, E; Herrero, A; Pardo, B; Adrover, E; Rifá, J; Godes, M J; Moyano, A; Cervantes, A

    2005-05-01

    The aim of this study was to determine whether the response rate for the paclitaxel-carboplatin combination is superior to carboplatin alone in the treatment of patients with platinum-sensitive recurrent ovarian carcinoma. Patients with recurrent ovarian carcinoma, 6 months after treatment with a platinum-based regimen and with no more than two previous chemotherapy lines, were randomized to receive carboplatin area under the curve (AUC) 5 (arm A) or paclitaxel 175 mg/m(2) + carboplatin AUC 5 (arm B). The primary end point was objective response, following a 'pick up the winner' design. Secondary end points included time to progression (TTP), overall survival, tolerability and quality of life (QoL). Eighty-one patients were randomized and included in the intention-to-treat analysis. The response rate in arm B was 75.6% [26.8% complete response (CR) + 48.8% partial response (PR)] [95% confidence interval (CI) 59.7% to 87.6%] and 50% in arm A (20% CR + 30% PR) (95% CI 33.8% to 66.2%). No significant differences were observed in grade 3-4 hematological toxicity. Conversely, mucositis, myalgia/arthralgia and peripheral neurophaty were more frequent in arm B. Median TTP was 49.1 weeks in arm B (95% CI 36.9-61.3) and 33.7 weeks in arm A (95% CI 25.8-41.5). No significant differences were found in the QoL analysis. Paclitaxel-carboplatin combination is a tolerable regimen with a higher response rate than carboplatin monotherapy in platinum-sensitive recurrent ovarian carcinoma.

  11. [Combination of adriamycin and cis-diammine-dichloro-platinum (II) in the treatment of advanced, therapy-resistant, ovarian carcinoma (author's transl)].

    Science.gov (United States)

    Cavalli, F; Stoller, U; Tschopp, L; Sonntag, R W; Brunner, K W

    1978-06-02

    Adriamycin (doxorubicin, Adriblastin) and cis-diammine-dichloro-platinum (II) (DDP, NSC 119 875) were used in the treatment of 18 patients with ovarian carcinoma, usually after intensive pre-treatment, both in a dosage of 50 mg/m2 once every 4 weeks. Forced diuresis was initiated at the same time. On average three such treatments were given. Six patients showed partial remission defined as decrease of tumour mass by more than 50% or as almost complete disappearance of ascites during more than two months without concomitant diuretic treatment. The remission time was 2+, 3, 3+, 3.5, 7+, and 9+ months. In all patients severe gastrointestinal toxicity occurred, however the myelosuppressive action was only moderate. Nephrotoxicity was negligible. Combined chemotherapy with Adriblastin and DDP thus seems effective even in intensively pretreated patients with ovarian carcinoma.

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

    DEFF Research Database (Denmark)

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

    2017-01-01

    BACKGROUND: Findings from in vitro studies suggest that increased exposure to thyroid hormones can influence progression of ovarian tumours. However, epidemiologic evidence on this topic is limited. METHODS: We pooled data from 11 studies from the Ovarian Cancer Association Consortium. Using mult...

  13. Quality of pathology reports for advanced ovarian cancer: are we missing essential information? An audit of 479 pathology reports from the EORTC-GCG 55971/NCIC-CTG OV13 neoadjuvant trial.

    Science.gov (United States)

    Verleye, Leen; Ottevanger, Petronella B; Kristensen, Gunnar B; Ehlen, Tom; Johnson, Nick; van der Burg, Maria E L; Reed, Nick S; Verheijen, René H M; Gaarenstroom, Katja N; Mosgaard, Berit; Seoane, Jose M; van der Velden, Jacobus; Lotocki, Robert; van der Graaf, Winette; Penninckx, Björn; Coens, Corneel; Stuart, Gavin; Vergote, Ignace

    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 chemotherapy and interval debulking surgery. Four hundred and seventy nine pathology reports from 40 institutions in 11 different countries were checked for the following quality indicators: macroscopic description of all specimens, measuring and weighing of major specimens, description of tumour origin and differentiation. All specimens were macroscopically described in 92.3% of the reports. All major samples were measured and weighed in 59.9% of the reports. A description of the origin of the tumour was missing in 20.5% of reports of the primary debulking group and in 23.4% of the interval debulking group. Assessment of tumour differentiation was missing in 10% of the reports after primary debulking and in 20.8% of the reports after interval debulking. Completeness of reports is positively correlated with accrual volume and adversely with hospital volume or type of hospital (academic versus non-academic). Quality of reports differs significantly by country. This audit of ovarian cancer pathology reports reveals that in a substantial number of reports basic pathologic data are missing, with possible adverse consequences for the quality of cancer care. Specialisation by pathologists and the use of standardised synoptic reports can lead to improved quality of reporting. Further research is needed to better define pre- and post-operative diagnostic criteria for ovarian cancer treated with neoadjuvant chemotherapy. Copyright © 2010 Elsevier Ltd. All rights reserved.

  14. FY2010 Annual Progress Report for Advanced Combustion Engine Research and Development

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Gurpreet [Office of Energy Efficiency and Renewable Energy (EERE), Washington, DC (United States)

    2010-12-01

    The Advanced Combustion Engine R&D subprogram supports the mission of the Vehicle Technologies Program by removing the critical technical barriers to commercialization of advanced internal combustion engines (ICEs) for passenger and commercial vehicles that meet future Federal emissions regulations. Dramatically improving the efficiency of ICEs and enabling their introduction in conventional as well as hybrid electric vehicles is the most promising and cost-effective approach to increasing vehicle fuel economy over the next 30 years.

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

    Directory of Open Access Journals (Sweden)

    Rhondali W

    2015-07-01

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

  16. Therapeutic Targeting of AXL Receptor Tyrosine Kinase Inhibits Tumor Growth and Intraperitoneal Metastasis in Ovarian Cancer Models

    Directory of Open Access Journals (Sweden)

    Pinar Kanlikilicer

    2017-12-01

    Full Text Available Despite substantial improvements in the treatment strategies, ovarian cancer is still the most lethal gynecological malignancy. Identification of drug treatable therapeutic targets and their safe and effective targeting is critical to improve patient survival in ovarian cancer. AXL receptor tyrosine kinase (RTK has been proposed to be an important therapeutic target for metastatic and advanced-stage human ovarian cancer. We found that AXL-RTK expression is associated with significantly shorter patient survival based on the The Cancer Genome Atlas patient database. To target AXL-RTK, we developed a chemically modified serum nuclease-stable AXL aptamer (AXL-APTAMER, and we evaluated its in vitro and in vivo antitumor activity using in vitro assays as well as two intraperitoneal animal models. AXL-aptamer treatment inhibited the phosphorylation and the activity of AXL, impaired the migration and invasion ability of ovarian cancer cells, and led to the inhibition of tumor growth and number of intraperitoneal metastatic nodules, which was associated with the inhibition of AXL activity and angiogenesis in tumors. When combined with paclitaxel, in vivo systemic (intravenous [i.v.] administration of AXL-aptamer treatment markedly enhanced the antitumor efficacy of paclitaxel in mice. Taken together, our data indicate that AXL-aptamers successfully target in vivo AXL-RTK and inhibit its AXL activity and tumor growth and progression, representing a promising strategy for the treatment of ovarian cancer.

  17. Primary ovarian leiomyoma

    International Nuclear Information System (INIS)

    Mathew, Marian; Krolikowski, Anderzj; Al-Haddabi, Ibrahim; Nirmala, Vadakkepat

    2005-01-01

    Ovarian leiomyoma is a rare and incidentally detected neoplasm, clinically indistinguishable from subserous leiomyomas and ovarian fibromas, until histopathological confirmation. We present a case of leiomyoma arising primarily from the ovary in a 35 year old woman. (author)

  18. Pathways to Genome-targeted Therapies in Serous Ovarian Cancer.

    Science.gov (United States)

    Axelrod, Joshua; Delaney, Joe

    2017-07-01

    Genome sequencing technologies and corresponding oncology publications have generated enormous publicly available datasets for many cancer types. While this has enabled new treatments, and in some limited cases lifetime management of the disease, the treatment options for serous ovarian cancer remain dismal. This review summarizes recent advances in our understanding of ovarian cancer, with a focus on heterogeneity, functional genomics, and actionable data.

  19. Irreversible neurological worsening following high-dose corticosteroids in advanced progressive multiple sclerosis

    NARCIS (Netherlands)

    Koch, M; De Keyser, J

    2006-01-01

    Background: A course of high-dose corticosteroids has been shown to hasten recovery from a relapse of multiple sclerosis (MS). Some patients with progressive MS ask for a course with corticosteroids outside a relapse, hoping to gain some functional improvement. Objective: To describe 4 patients with

  20. Conference Scene: From innovative polymers to advanced nanomedicine: Key challenges, recent progress and future perspectives

    NARCIS (Netherlands)

    Feijen, Jan; Hennink, W.E.; Zhong, Zhiyuan

    2013-01-01

    Recent developments in polymer-based controlled delivery systems have made a significant clinical impact. The second Symposium on Innovative Polymers for Controlled Delivery (SIPCD) was held in Suzhou, China to address the key challenges and provide up-to-date progress and future perspectives in the

  1. 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....

  2. Everolimus in advanced, progressive, well-differentiated, non-functional neuroendocrine tumors: RADIANT-4 lung subgroup analysis.

    Science.gov (United States)

    Fazio, Nicola; Buzzoni, Roberto; Delle Fave, Gianfranco; Tesselaar, Margot E; Wolin, Edward; Van Cutsem, Eric; Tomassetti, Paola; Strosberg, Jonathan; Voi, Maurizio; Bubuteishvili-Pacaud, Lida; Ridolfi, Antonia; Herbst, Fabian; Tomasek, Jiri; Singh, Simron; Pavel, Marianne; Kulke, Matthew H; Valle, Juan W; Yao, James C

    2018-01-01

    In the phase III RADIANT-4 study, everolimus improved median progression-free survival (PFS) by 7.1 months in patients with advanced, progressive, well-differentiated (grade 1 or grade 2), non-functional lung or gastrointestinal neuroendocrine tumors (NETs) vs placebo (hazard ratio, 0.48; 95% confidence interval [CI], 0.35-0.67; P < .00001). This exploratory analysis reports the outcomes of the subgroup of patients with lung NETs. In RADIANT-4, patients were randomized (2:1) to everolimus 10 mg/d or placebo, both with best supportive care. This is a post hoc analysis of the lung subgroup with PFS, by central radiology review, as the primary endpoint; secondary endpoints included objective response rate and safety measures. Ninety of the 302 patients enrolled in the study had primary lung NET (everolimus, n = 63; placebo, n = 27). Median PFS (95% CI) by central review was 9.2 (6.8-10.9) months in the everolimus arm vs 3.6 (1.9-5.1) months in the placebo arm (hazard ratio, 0.50; 95% CI, 0.28-0.88). More patients who received everolimus (58%) experienced tumor shrinkage compared with placebo (13%). Most frequently reported (≥5% incidence) grade 3-4 drug-related adverse events (everolimus vs. placebo) included stomatitis (11% vs. 0%), hyperglycemia (10% vs. 0%), and any infections (8% vs. 0%). In patients with advanced, progressive, well-differentiated, non-functional lung NET, treatment with everolimus was associated with a median PFS improvement of 5.6 months, with a safety profile similar to that of the overall RADIANT-4 cohort. These results support the use of everolimus in patients with advanced, non-functional lung NET. The trial is registered with ClinicalTrials.gov (no. NCT01524783). © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  3. Progress in development and design aspects of advanced water cooled reactors

    International Nuclear Information System (INIS)

    1992-12-01

    The objective of the Technical Committee Meeting (TCM) was to provide an international forum for technical specialists to review and discuss technology developments and design work for advanced water cooled reactors, safety approaches and features of current water cooled reactors and to identify, understand and describe advanced features for safety and operational improvements. The TCM was attended by 92 participants representing 18 countries and two international organizations and included 40 presentations by authors of 14 countries and one international organization. A separate abstract was prepared for each of these presentations. Refs, figs, tabs

  4. Ceramic technology for advanced heat engines project: Semiannual progress report for April through September 1986

    Energy Technology Data Exchange (ETDEWEB)

    1987-03-01

    An assessment of needs was completed, and a five-year project plan was developed with extensive input from private industry. Objective is to develop the industrial technology base required for reliable ceramics for application in advanced automotive heat engines. The project approach includes determining the mechanisms controlling reliability, improving processes for fabricating existing ceramics, developing new materials with increased reliability, and testing these materials in simulated engine environments to confirm reliability. Although this is a generic materials project, the focus is on structural ceramics for advanced gas turbine and diesel engines, ceramic bearings and attachments, and ceramic coatings for thermal barrier and wear applications in these engines.

  5. Progress on the Design of the Storage Ring Vacuum System for the Advanced Photon Source Upgrade Project

    Energy Technology Data Exchange (ETDEWEB)

    Stillwell, B.; Billett, B.; Brajuskovic, B.; Carter, J.; Kirkus, E.; Lale, M.; Lerch, J.; Noonan, J.; O' Neill, M.; Rocke, B.; Suthar, K.; Walters, D.; Wiemerslage, G.; Zientek, J.

    2017-06-20

    Recent work on the design of the storage ring vacuum system for the Advanced Photon Source Upgrade project (APS-U) includes: revising the vacuum system design to accommodate a new lattice with reverse bend magnets, modifying the designs of vacuum chambers in the FODO sections for more intense incident synchrotron radiation power, modifying the design of rf-shielding bellows liners for better performance and reliability, modifying photon absorber designs to make better use of available space, and integrated planning of components needed in the injection, extraction and rf cavity straight sections. An overview of progress in these areas is presented.

  6. Recent Progresses and Development of Advanced Atomic Layer Deposition towards High-Performance Li-Ion Batteries

    Science.gov (United States)

    Lu, Wei; Liang, Longwei; Sun, Xuan; Sun, Xiaofei; Wu, Chen; Hou, Linrui; Sun, Jinfeng

    2017-01-01

    Electrode materials and electrolytes play a vital role in device-level performance of rechargeable Li-ion batteries (LIBs). However, electrode structure/component degeneration and electrode-electrolyte sur-/interface evolution are identified as the most crucial obstacles in practical applications. Thanks to its congenital advantages, atomic layer deposition (ALD) methodology has attracted enormous attention in advanced LIBs. This review mainly focuses upon the up-to-date progress and development of the ALD in high-performance LIBs. The significant roles of the ALD in rational design and fabrication of multi-dimensional nanostructured electrode materials, and finely tailoring electrode-electrolyte sur-/interfaces are comprehensively highlighted. Furthermore, we clearly envision that this contribution will motivate more extensive and insightful studies in the ALD to considerably improve Li-storage behaviors. Future trends and prospects to further develop advanced ALD nanotechnology in next-generation LIBs were also presented. PMID:29036916

  7. Progress with situation assessment and risk prediction in advanced driver assistance systems : A survey

    NARCIS (Netherlands)

    Rendon-Velez, E.; Horváth, I.; Opiyo, E.Z.

    2009-01-01

    In the field of automotive safety, advanced driver assistance systems (ADAS) are receiving growing attention. Effective ADAS requires awareness of the actual driving situation, a reliable assessment of the risks, and making rapid decisions on assisting actions. This paper reviews the current

  8. Predicting 6- and 12-Month Risk of Mortality in Patients With Platinum-Resistant Advanced-Stage Ovarian Cancer: Prognostic Model to Guide Palliative Care Referrals.

    Science.gov (United States)

    Foote, Jonathan; Lopez-Acevedo, Micael; Samsa, Gregory; Lee, Paula S; Kamal, Arif H; Alvarez Secord, Angeles; Havrilesky, Laura J

    2018-02-01

    Predictive models are increasingly being used in clinical practice. The aim of the study was to develop a predictive model to identify patients with platinum-resistant ovarian cancer with a prognosis of less than 6 to 12 months who may benefit from immediate referral to hospice care. A retrospective chart review identified patients with platinum-resistant epithelial ovarian cancer who were treated at our institution between 2000 and 2011. A predictive model for survival was constructed based on the time from development of platinum resistance to death. Multivariate logistic regression modeling was used to identify significant survival predictors and to develop a predictive model. The following variables were included: time from diagnosis to platinum resistance, initial stage, debulking status, number of relapses, comorbidity score, albumin, hemoglobin, CA-125 levels, liver/lung metastasis, and the presence of a significant clinical event (SCE). An SCE was defined as a malignant bowel obstruction, pleural effusion, or ascites occurring on or before the diagnosis of platinum resistance. One hundred sixty-four patients met inclusion criteria. In the regression analysis, only an SCE and the presence of liver or lung metastasis were associated with poorer short-term survival (P < 0.001). Nine percent of patients with an SCE or liver or lung metastasis survived 6 months or greater and 0% survived 12 months or greater, compared with 85% and 67% of patients without an SCE or liver or lung metastasis, respectively. Patients with platinum-resistant ovarian cancer who have experienced an SCE or liver or lung metastasis have a high risk of death within 6 months and should be considered for immediate referral to hospice care.

  9. The effect of angiotensin-converting-enzyme inhibitors on progression of advanced polycystic kidney disease

    DEFF Research Database (Denmark)

    Jafar, Tazeen H; Stark, Paul C; Schmid, Christopher H

    2005-01-01

    BACKGROUND: It is not known whether angiotensin-converting-enzyme (ACE) inhibitors slow the progression of polycystic kidney disease (PKD). We performed a patient-level meta-analysis to compare the effect of antihypertensive regimens, including ACE inhibitors, to those without ACE inhibitors...... of doubling of baseline serum creatinine or onset of kidney failure). We also performed multivariable linear regression and Cox proportional hazards analyses. Based on previous findings, we searched for interactions between the treatment effect (effect of ACE inhibitors vs. controls) and baseline urine......%) in the ACE inhibitor group and 30 patients (41%) in the control group (P= 0.17). ACE inhibitors had a greater effect on lowering urine protein excretion and slowing kidney disease progression in patients with higher levels of baseline urine protein excretion (interaction P

  10. Anthropometric characteristics and ovarian cancer risk and survival.

    Science.gov (United States)

    Minlikeeva, Albina N; Moysich, Kirsten B; Mayor, Paul C; Etter, John L; Cannioto, Rikki A; Ness, Roberta B; Starbuck, Kristen; Edwards, Robert P; Segal, Brahm H; Lele, Sashikant; Odunsi, Kunle; Diergaarde, Brenda; Modugno, Francesmary

    2018-02-01

    Multiple studies have examined the role of anthropometric characteristics in ovarian cancer risk and survival; however, their results have been conflicting. We investigated the associations between weight change, height and height change and risk and outcome of ovarian cancer using data from a large population-based case-control study. Data from 699 ovarian cancer cases and 1,802 controls who participated in the HOPE study were included. We used unconditional logistic regression adjusted for age, race, number of pregnancies, use of oral contraceptives, and family history of breast or ovarian cancer to examine the associations between self-reported height and weight and height change with ovarian cancer risk. Cox proportional hazards regression models adjusted for age and stage were used to examine the association between the exposure variables and overall and progression-free survival among ovarian cancer cases. We observed an increased risk of ovarian cancer mortality and progression for gaining more than 20 pounds between ages 18-30, HR 1.36; 95% CI 1.05-1.76, and HR 1.31; 95% CI 1.04-1.66, respectively. Losing weight and gaining it back multiple times was inversely associated with both ovarian cancer risk, OR 0.78; 95% CI 0.63-0.97 for 1-4 times and OR 0.73; 95% CI 0.54-0.99 for 5-9 times, and mortality, HR 0.63; 95% CI 0.40-0.99 for 10-14 times. Finally, being taller during adolescence and adulthood was associated with increased risk of mortality. Taller stature and weight gain over lifetime were not related to ovarian cancer risk. Our results suggest that height and weight and their change over time may influence ovarian cancer risk and survival. These findings suggest that biological mechanisms underlying these associations may be hormone driven and may play an important role in relation to ovarian carcinogenesis and tumor progression.

  11. Ceramic technology for advanced heat engines project. Semiannual progress report, April-September 1985

    Energy Technology Data Exchange (ETDEWEB)

    1986-05-01

    An assessment of needs was completed, and a five-year project plan was developed with input from private industry. Objective is to develop the industrial technology base required for reliable ceramics for application in advanced automotive heat engines. Focus is on structural ceramics for advanced gas turbine and diesel engines, ceramic bearings and attachments, and ceramic coatings for thermal barrier and wear applications in these engines. The work described in this report is organized according to the following WBS project elements: management and coordination; materials and processing (monolithics, ceramic composites, thermal and wear coatings, joining); materials design methodology (contact interfaces, new concepts); data base and life prediction (time-dependent behavior, environmental effects, fracture mechanics, NDE development); and technology transfer. This report includes contributions from all currently active project participants.

  12. Center for Technology for Advanced Scientific Component Software (TASCS) Consolidated Progress Report July 2006 - March 2009

    Energy Technology Data Exchange (ETDEWEB)

    Bernholdt, D E; McInnes, L C; Govindaraju, M; Bramley, R; Epperly, T; Kohl, J A; Nieplocha, J; Armstrong, R; Shasharina, S; Sussman, A L; Sottile, M; Damevski, K

    2009-04-14

    A resounding success of the Scientific Discovery through Advanced Computing (SciDAC) program is that high-performance computational science is now universally recognized as a critical aspect of scientific discovery [71], complementing both theoretical and experimental research. As scientific communities prepare to exploit unprecedented computing capabilities of emerging leadership-class machines for multi-model simulations at the extreme scale [72], it is more important than ever to address the technical and social challenges of geographically distributed teams that combine expertise in domain science, applied mathematics, and computer science to build robust and flexible codes that can incorporate changes over time. The Center for Technology for Advanced Scientific Component Software (TASCS) tackles these issues by exploiting component-based software development to facilitate collaborative high-performance scientific computing.

  13. Progress towards advanced practice roles in Australia, New Zealand and the Western Pacific

    International Nuclear Information System (INIS)

    Smith, Tony; Yielder, Jill; Ajibulu, Olusegun; Caruana, Edward

    2008-01-01

    This paper describes the evolution and current status of advanced practice in medical imaging and radiation therapy in the Oceania region. To date development has been slow, largely ad hoc and based on local needs. Most advanced practice is informal or is regarded as part of the core skills of some individual practitioners. However, recently, there have been signs of change taking place, with a more coordinated and collaborative approach to role development becoming evident. In Australia, although a number of reports and papers have discussed extended clinical roles, especially for diagnostic Radiographers, no concrete action has yet taken place in either discipline. Stakeholders apparently agree that existing extended roles should be formalised, however, and that continuing education must underpin future role extension initiatives. A three-level professional structure, including an advanced practitioner level, has been accepted by the New Zealand Institute of Medical Radiation Technology (NZIMRT), with the support of the District Health Boards of New Zealand (DHBNZ). Implementation is expected to begin before the end of 2008. Meanwhile, recognition of the serious lack of Radiologists in Western Pacific Island Nations led to the training of some Radiographers in radiological interpretation of images between 2004 and 2006. The aim was to up-skill the Radiographers so that they could more reliably flag abnormalities to doctors, a model that may be applicable elsewhere. It is argued that future practice models must include advanced practice roles in order to safely meet the growing demand for medical radiation services. Local factors, such as the structure of the health care system and the depth of engagement of the key stakeholders in planning and implementation, however, are expected to influence the evolution of new clinical practice models in the region

  14. Definitions for response and progression in ovarian cancer clinical trials incorporating RECIST 1.1 and CA 125 agreed by the Gynecological Cancer Intergroup (GCIG)

    DEFF Research Database (Denmark)

    Rustin, Gordon John Sampson; Vergote, Ignace; Eisenhauer, Elizabeth

    2011-01-01

    . Thus, we recommend that the definitions described later in detail are incorporated into clinical trial protocols to maintain consistency. The criteria for defining progression are now acceptable in clinical trials of recurrent disease as they have since been validated (Pujade-Lauraine, personal...... communication, 2010). The GCIG requests that data from all clinical trials using these definitions are made available to GCIG trial centers so that continual validation and improvement can be accomplished. These definitions were developed from analyzing patients receiving cytotoxic chemotherapy and have not yet......The Gynecological Cancer Intergroup (GCIG) has previously reached consensus regarding the criteria that should be used in clinical trial protocols to define progression-free survival after first-line therapy as well as the criteria to define response to treatment in recurrent disease using...

  15. ICG-fluorescence imaging for detection of peritoneal metastases and residual tumoral scars in locally advanced ovarian cancer: A pilot study.

    Science.gov (United States)

    Veys, Isabelle; Pop, Florin-Catalin; Vankerckhove, Sophie; Barbieux, Romain; Chintinne, Marie; Moreau, Michel; Nogaret, Jean-Marie; Larsimont, Denis; Donckier, Vincent; Bourgeois, Pierre; Liberale, Gabriel

    2018-02-01

    No intraoperative imaging techniques exist for detecting tumor nodules or tumor scar tissues in patients treated with upfront or interval cytoreductive surgery (CS) after neoadjuvant chemotherapy (NAC). The aims of this study were to evaluate the role of indocyanine green (ICG) fluorescence imaging (FI) for the detection of peritoneal metastases (PM) and evaluate whether it can be used to detect remnant tumor cells in scar tissue. Patients with PM from ovarian cancer admitted for CS were included. ICG, at 0.25 mg per kg of patient weight, was injected intraoperatively after explorative laparotomy before CS. A total of 108 peritoneal lesions, including 25 scars, were imaged in 20 patients. Seventy-three were malignant (67.6%) and 35 benign (32.4%). The mean Tumor to Background Ratio (ex vivo) was 1.8 (SD 1.3) in malignant and 1.0 (SD 0.79) in benign nodules (P = 0.007). Of 25 post-NAC scars, the mean Tumor to Background Ratio (TBR) (in vivo) was 2.06 (SD 1.15) in malignant and 1.21 (SD 0.50) in benign nodules (P = 0.26). The positive predictive value of ICG-FI to detect tumor cells in scars was 57.1%. ICG-FI is accurate to demonstrate PM in ovarian cancer but unable to discriminate between benign and malignant post-NAC. © 2017 Wiley Periodicals, Inc.

  16. Evaluation of the ovarian reserve in women transplanted with frozen and thawed ovarian cortical tissue

    DEFF Research Database (Denmark)

    Greve, Tine; Schmidt, Kirsten Tryde; Kristensen, Stine Gry

    2012-01-01

    To investigate ovarian reserve and ovarian function in women transplanted with frozen/thawed ovarian tissue.......To investigate ovarian reserve and ovarian function in women transplanted with frozen/thawed ovarian tissue....

  17. Phase II trial of pazopanib in advanced/progressive malignant pheochromocytoma and paraganglioma.

    Science.gov (United States)

    Jasim, Sina; Suman, Vera J; Jimenez, Camilo; Harris, Pamela; Sideras, Kostandinos; Burton, Jill K; Worden, Francis Paul; Auchus, Richard J; Bible, Keith C

    2017-08-01

    Pheochromocytomas and paragangliomas (Pheo/PGL) are rare, vascular, sometimes malignant endocrine tumors. Case reports indicate the activity of vascular endothelium growth factor receptor-targeted kinase inhibitors in these cancers. To assess the antitumor activity and tolerability of pazopanib in progressive malignant Pheo/PGL. This multicenter Phase II trial (MC107C) enrolled individuals  ≥18 years old with disease progression ≤ 6 months prior to registration, Eastern Cooperative Oncology Group PS 0-2, and measurable disease (response evaluation criteria in solid tumors 1.0). Pazopanib was administered in 28-day cycles, with the regimen ultimately being as follows: cycle 1: 400 mg daily on days 1-14, cycle 2: 800 mg daily on days 1-14, and then cycle 2 + : 800 mg daily on all days. The study was halted due to poor accrual. Seven patients were enrolled (05/2011-11/2014). One patient withdrew consent prior to treatment, leaving six evaluable patients. Treatment was discontinued, due to the following reasons: disease progression (4); withdrawal (1); and grade 4 (Takotsubo) cardiomyopathy (1). The median number of cycles administered was 4 (range: 2-29, total: 49). Four patients had >1 dose reduction due to the following reasons: fatigue (1), abnormal liver tests (2), hypertension and (Takotsubo) cardiomyopathy (1), and headaches (1). Common severe (Common Terminology Criteria for Adverse Events v3.0 grades 3-5) toxicities were as follows: hypertension (3/6), (Takotsubo) cardiomyopathy (2/6), diarrhea (1/6), fatigue (1/6), headache (1/6), and hematuria (1/6). One confirmed partial response was observed in PGL (17%, duration 2.4 years); median progression-free survival and overall survival were 6.5 and 14.8 months, respectively. Pazopanib has activity in Pheo/PGL requiring more study; optimal alpha- and beta-blockade are imperative pre-therapy in patients with secretory tumors, as risk of hypertension and cardiomyopathy are potentially life

  18. FY 2014 Annual Progress Report - Advanced Combustion Engine Research and Development (Book)

    Energy Technology Data Exchange (ETDEWEB)

    2014-11-01

    In the past year, the DOE Hydrogen Program (the Program) made substantial progress toward its goals and objectives. The Program has conducted comprehensive and focused efforts to enable the widespread commercialization of hydrogen and fuel cell technologies in diverse sectors of the economy. With emphasis on applications that will effectively strengthen our nation's energy security and improve our stewardship of the environment, the Program engages in research, development, and demonstration of critical improvements in the technologies. Highlights of the Program's accomplishments can be found in the sub-program chapters of this report.

  19. FY2011 Advanced Power Electronics and Electric Motors Annual Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    Rogers, Susan A. [Office of Energy Efficiency and Renewable Energy (EERE), Washington, DC (United States)

    2012-01-31

    The Advanced Power Electronics and Electric Motors (APEEM) program within the DOE Vehicle Technologies Program (VTP) provides support and guidance for many cutting-edge automotive technologies now under development. Research is focused on developing revolutionary new power electronics (PE), electric motor (EM), thermal management, and traction drive system technologies that will leapfrog current on-the-road technologies. The research and development (R&D) is also aimed at achieving a greater understanding of and improvements in the way the various new components of tomorrow’s automobiles will function as a unified system to improve fuel efficiency.

  20. FY2010 Annual Progress Report for Advanced Power Electronics and Electric Motors

    Energy Technology Data Exchange (ETDEWEB)

    Rogers, Susan A. [Office of Energy Efficiency and Renewable Energy (EERE), Washington, DC (United States)

    2011-01-01

    The Advanced Power Electronics and Electric Machines (APEEM) subprogram within the Vehicle Technologies Program provides support and guidance for many cutting-edge automotive technologies now under development. Research is focused on developing revolutionary new power electronics (PE) and electric motor technologies that will leapfrog current on-the-road technologies. The research and development (R&D) is also aimed at achieving a greater understanding of and improvements in the way the various new components of tomorrow’s automobiles will function as a unified system to improve fuel efficiency.

  1. Clinical Cancer Advances 2018: Annual Report on Progress Against Cancer From the American Society of Clinical Oncology.

    Science.gov (United States)

    Heymach, John; Krilov, Lada; Alberg, Anthony; Baxter, Nancy; Chang, Susan Marina; Corcoran, Ryan; Dale, William; DeMichele, Angela; Magid Diefenbach, Catherine S; Dreicer, Robert; Epstein, Andrew S; Gillison, Maura L; Graham, David L; Jones, Joshua; Ko, Andrew H; Lopez, Ana Maria; Maki, Robert G; Rodriguez-Galindo, Carlos; Schilsky, Richard L; Sznol, Mario; Westin, Shannon Neville; Burstein, Harold

    2018-04-01

    A MESSAGE FROM ASCO'S PRESIDENT I remember when ASCO first conceived of publishing an annual report on the most transformative research occurring in cancer care. Thirteen reports later, the progress we have chronicled is remarkable, and this year is no different. The research featured in ASCO's Clinical Cancer Advances 2018 report underscores the impressive gains in our understanding of cancer and in our ability to tailor treatments to tumors' genetic makeup. The ASCO 2018 Advance of the Year, adoptive cell immunotherapy, allows clinicians to genetically reprogram patients' own immune cells to find and attack cancer cells throughout the body. Chimeric antigen receptor (CAR) T-cell therapy-a type of adoptive cell immunotherapy-has led to remarkable results in young patients with acute lymphoblastic leukemia (ALL) and in adults with lymphoma and multiple myeloma. Researchers are also exploring this approach in other types of cancer. This advance would not be possible without robust federal investment in cancer research. The first clinical trial of CAR T-cell therapy in children with ALL was funded, in part, by grants from the National Cancer Institute (NCI), and researchers at the NCI Center for Cancer Research were the first to report on possible CAR T-cell therapy for multiple myeloma. These discoveries follow decades of prior research on immunology and cancer biology, much of which was supported by federal dollars. In fact, many advances that are highlighted in the 2018 Clinical Cancer Advances report were made possible thanks to our nation's support for biomedical research. Funding from the US National Institutes of Health and the NCI helps researchers pursue critical patient care questions and addresses vital, unmet needs that private industry has little incentive to take on. Federally supported cancer research generates the biomedical innovations that fuel the development and availability of new and improved treatments for patients. We need sustained federal

  2. Paclitaxel: a pharmacoeconomic review of its use in the treatment of ovarian cancer.

    Science.gov (United States)

    Young, M; Plosker, G L

    2001-01-01

    Paclitaxel belongs to the group of antitumour agents called the taxanes. Its efficacy in advanced ovarian cancer has been established in large, randomised phase III clinical trials. When used in combination with cisplatin for first-line treatment of advanced ovarian cancer, it is superior to cyclophosphamide/cisplatin, with gains in median survival of around 1 year. Paclitaxel plus carboplatin has similar efficacy to paclitaxel plus cisplatin. There is now consensus that paclitaxel plus either carboplatin or cisplatin is the recommended first-line therapy for patients with advanced ovarian cancer. The particular combination employed may vary between institutions and geographical regions, although paclitaxel plus carboplatin is generally better tolerated (i.e. lower incidence of non-haematological adverse events) than paclitaxel plus cisplatin and is widely used in many countries. Paclitaxel is also used as monotherapy in second-line (salvage) treatment of ovarian cancer. Pharmacoeconomic analyses performed to date have primarily focused on first-line therapy comparing the combination of paclitaxel/cisplatin with cyclophosphamide/cisplatin. All studies incorporated clinical outcomes data, most commonly from the Gynecologic Oncology Group (GOG) 111 trial, showing a survival advantage for paclitaxel/cisplatin. These studies report incremental cost-effectiveness ratios (ICERs) ranging from $US 6395 per additional life-year gained (LYG) in Spain (1995/96 values) to $US 44,690 per additional progression-free LYG in France (year of costs not reported). Five studies were based in the US and Canada and these reported very similar ICERs of $US 13,135 (year of costs not reported) to $US 25,131 (1993 costs) per additional LYG. In all of these studies the incremental costs of paclitaxel/cisplatin therapy fall well within the commonly cited threshold limit of $US 50,000 for new therapies and compare well with incremental costs reported for other oncological and life

  3. Ceramic technology for advanced heat engines project: Semiannual progress report, October 1986-March 1987

    Energy Technology Data Exchange (ETDEWEB)

    1987-08-01

    This report contains four subelements: (1) Monolithics, (2) Ceramic Composites, (3) Thermal and Wear Coatings, and (4) Joining. Ceramic research conducted within the Monolithics subelement currently includes work activities on green state ceramic fabrication, characterization, and densification and on structural, mechanical, and physical properties of these ceramics. Research conducted within the Ceramic Composites subelement currently includes silicon carbide and oxide-based composites, which, in addition to the work activities cited for Monolithics, include fiber synthesis and characterization. Research conducted in the Thermal and Wear Coatings subelement is currently limited to oxide-base coatings and involves coating synthesis, characterization, and determination of the mechanical and physical properties of the coatings. Research conducted in the Joining subelement currently includes studies of processes to produce strong stable joints between zirconia ceramics and iron-base alloys. A major objective of the research in the Materials and Processing project element is to systematically advance the understanding of the relationships between ceramic raw materials such as powders and reactant gases, the processing variables involved in producing the ceramic materials, and the resultant microstructures and physical and mechanical properties of the ceramic materials. Success in meeting this objective will provide US companies with new or improved ways for producing economical highly reliable ceramic components for advanced heat engines.

  4. Progress on PRISM, an inherently safe, economic, and testable advanced liquid metal reactor

    International Nuclear Information System (INIS)

    Tippets, F.E.; Salerno, L.N.; Boardman, C.E.; Kwant, W.; Murata, R.E.; Snyder, C.R.

    1987-01-01

    This paper reports progress on the design of PRISM (Power Reactor Inherently Safe Module) under the DOE-sponsored innovative reactor program now in its third year at General Electric. The purpose of this program is to develop a design for an inherently safe, reliable, and marketable liquid metal fast reactor power plant. The PRISM design approach includes the following key elements: Compact sodium-cooled pool-type reactor modules that are sized to enable factory fabrication, economical shipment to inland as well as water-side sites, and economical full-scale prototype testing for design certification; Nuclear safety-related envelope limited to the reactor modules and their service systems; Inherent, passive shutdown heat removal for loss-of-cooling events; Inherent, passive reactivity shutdown for failure-to-scram events

  5. Chromosomal Alterations and Gene Expression Changes Associated with the Progression of Leukoplakia to Advanced Gingivobuccal Cancer

    Directory of Open Access Journals (Sweden)

    Priyanka G. Bhosale

    2017-06-01

    Full Text Available We present an integrative genome-wide analysis that can be used to predict the risk of progression from leukoplakia to oral squamous cell carcinoma (OSCC arising in the gingivobuccal complex (GBC. We find that the genomic and transcriptomic profiles of leukoplakia resemble those observed in later stages of OSCC and that several changes are associated with this progression, including amplification of 8q24.3, deletion of 8p23.2, and dysregulation of DERL3, EIF5A2, ECT2, HOXC9, HOXC13, MAL, MFAP5 and NELL2. Comparing copy number profiles of primary tumors with and without lymph-node metastasis, we identify alterations associated with metastasis, including amplifications of 3p26.3, 8q24.21, 11q22.1, 11q22.3 and deletion of 8p23.2. Integrative analysis reveals several biomarkers that have never or rarely been reported in previous OSCC studies, including amplifications of 1p36.33 (attributable to MXRA8, 3q26.31 (EIF5A2, 9p24.1 (CD274, and 12q13.2 (HOXC9 and HOXC13. Additionally, we find that amplifications of 1p36.33 and 11q22.1 are strongly correlated with poor clinical outcome. Overall, our findings delineate genomic changes that can be used in treatment management for patients with potentially malignant leukoplakia and OSCC patients with higher risk of lymph-node metastasis.

  6. Sustained systemic response paralleled with ovarian metastasis progression by sunitinib in metastatic renal cell carcinoma: Is this an anti-angiogenic potentiation of cancer?

    Directory of Open Access Journals (Sweden)

    Uttam K Mete

    2015-01-01

    Full Text Available Metastatic renal cell cancer is associated with poor prognosis and survival and is resistant to conventional chemotherapy. Therapeutic targeting of molecular pathways for tumor angiogenesis and other specific activation mechanisms offers improved tumor response and prolonged survival. A 48-year-old, female patient presented with large right renal mass with features suggesting of renal cell cancer without metastasis on contrast enhanced computed tomography (CT. Right radical nephrectomy was done. After 9 months of surgery, she got metastasis in lung, liver and ovary. The patient received sunitinib via an expanded access program. After eight 6-week cycles of sunitinib, a reassessment CT scan confirmed an excellent partial response with the almost complete disappearance (90% of liver and lung metastasis but the adnexal mass had increased in size (>10 times and the possibility was thought of second malignancy. Excision of the mass performed. Histopathology of the mass depicted metastatic renal cell cancer. There is possibility of a ′site-specific anti-angiogenic potentiation mechanism′ of malignancy in relation to sunitinib based upon the preclinical studies, in reference to the index case. Regression of one site with concurrent progression is possible. The exact mechanism of site-specific response, especially organ specific progression by vascular endothelial growth factor inhibitors in metastatic renal cell cancer warrants further study.

  7. Towards an advanced design for MYRRHA. Development of the primary system is progressively taking shape

    International Nuclear Information System (INIS)

    2015-01-01

    In recent years, the Belgian Nuclear Research Centre SCK-CEN has been developing a versatile irradiation facility, which will replace the current BR2 research reactor in the future. This 'Multi-purpose hYbrid Research Reactor for High-tech Applications', MYRRHA for short, is designed to be a system driven by an accelerator (Advanced Nuclear System or ADS). Such an ADS consists of a particle accelerator linked to a subcritical reactor. MYRRHA is also able to operate in critical mode like a classic reactor. Scientists and engineers have been working on the development of the MYRRHA reactor without interruption since 1998. A new revision in 2014 again brought them a step closer to completion. The article discusses the current status and several challenges, related to both the budget and the technical aspects of the design.

  8. Special issue on the "Consortium for Advanced Simulation of Light Water Reactors Research and Development Progress"

    Science.gov (United States)

    Turinsky, Paul J.; Martin, William R.

    2017-04-01

    In this special issue of the Journal of Computational Physics, the research and development completed at the time of manuscript submission by the Consortium for Advanced Simulation of Light Water Reactors (CASL) is presented. CASL is the first of several Energy Innovation Hubs that have been created by the Department of Energy. The Hubs are modeled after the strong scientific management characteristics of the Manhattan Project and AT&T Bell Laboratories, and function as integrated research centers that combine basic and applied research with engineering to accelerate scientific discovery that addresses critical energy issues. Lifetime of a Hub is expected to be five or ten years depending upon performance, with CASL being granted a ten year lifetime.

  9. Topotecan Monotherapy in Heavily Pretreated Patients with Progressive Advanced Stage Neuroendocrine Carcinomas

    DEFF Research Database (Denmark)

    Olsen, Ingrid Marie Holst; Knigge, Ulrich; Federspiel, Birgitte

    2014-01-01

    BACKGROUND: Neuroendocrine carcinomas (WHO grade 3) are highly aggressive tumors with an immense tendency to metastasize and with a poor prognosis. In advanced disease, there is no standard treatment beyond first-line platin/etoposide-based chemotherapy. Topotecan is widely used as second...... neuroendocrine carcinomas (Ki67>20%, G3) successively treated with oral topotecan 2.3 mg/m(2) d1-5 every 3 weeks. All patients had previously received treatment with carboplatin/etoposide. Demographic, clinical and pathological features were recorded. CT-evaluations according to RECIST 1.1 were performed after...... every three courses. Hematological toxicity was assessed by CTC-criteria. RESULTS: Twenty-two eligible patients received a median of 2 courses [range1-6]. Median age: 65 years [35-77]. Male/female: 11/11. Median Ki-67 index: 95% [25-100%]. Median number previous chemotherapy regimens: 2 [1-3]. All...

  10. FY2013 Advanced Power Electronics and Electric Motors R&D Annual Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    Rogers, Susan A. [Dept. of Energy (DOE), Washington DC (United States). Vehicle Technologies Office

    2014-02-01

    The Advanced Power Electronics and Electric Motors (APEEM) technology area within the DOE Vehicle Technologies Office (VTO) provides support and guidance for many cutting-edge automotive technologies now under development. Research is focused on developing revolutionary new power electronics (PE), electric motor, and traction drive system (TDS) technologies that will leapfrog current on-the-road technologies, leading to lower cost and better efficiency in transforming battery energy to useful work. The research and development (R&D) is also aimed at achieving a greater understanding of and improvements in the way the various new components of tomorrow’s automobiles will function as a unified system to improve fuel efficiency through research in more efficient TDSs.

  11. Advanced direct liquefaction concepts for PETC generic units. Quarterly technical progress report, January--March 1992

    Energy Technology Data Exchange (ETDEWEB)

    1992-04-01

    In the Advance Coal Liquefaction Concept Proposal (ACLCP) carbon monoxide (CO) and water have been proposed as the primary reagents in the pretreatment process. The main objective of this project is to develop a methodology for pretreating coal under mild conditions based on a combination of existing processes which have shown great promise in liquefaction, extraction and pyrolysis studies. The aim of this pretreatment process is to partially depolymerise the coal, eliminate oxygen and diminish the propensity for retograde reactions during subsequent liquefaction. The desirable outcome of the CO pretreatment step should be: (1) enhanced liquefaction activity and/or selectivity toward products of higher quality due to chemical modification of the coal structure; (2) cleaner downstream products; (3) overall improvement in operability and process economics.

  12. Breeding high yielding, high protein spring wheats: Problems, progress and approaches to further advances

    International Nuclear Information System (INIS)

    Konzak, C.F.; Rubenthaler, G.L.

    1984-01-01

    Preliminary data offer promise that advances have been made in breeding hard red spring wheat selections with a yielding capacity about equal to current cultivars and with an increased capacity for producing high protein grain. The most promising new selections are derivatives of Magnif 41M1, CI17689, a semi-dwarf mutant of an Argentinian high protein cultivar. Rapid changes in disease and pest problems also required immediate attention and a reorientation of breeding materials and goals. Selection procedures suggested as promising include early generation (F 2 and F 3 ) screening for disease resistance and agronomic type, with screening for protein content delayed until F 4 or F 5 . Cultural conditions conducive for expressing the highest yield capacity are proposed as optimum for identifying those selections also able to produce high protein grain. A goal of routine production of 14.5% (or higher) protein grain is considered necessary and achievable under fertility management conditions required for maximum yield expression of agronomically competitive cultivars. Agronomically improved sources of high protein genes, an increasing number of induced high protein mutants, and numerous high protein crossbred derivatives of T. dicoccoides and Aegilops species have recently become available. These new or improved germplasm sources as well as a considerable reserve of yet untapped germplasm variability in other accessions of wild T. dicoccoides offer increased optimism that further, rapid advances in the breeding of adapted high yielding, high protein wheats are achievable. Improved breeding schemes, using induced male sterility mutants either to aid in crossing or to develop male sterile facilitated recurrent selection (MSFRS) populations, should contribute towards an earlier achievement of the desired goal while providing the basis for buffering against rapid changes in disease and pest problems

  13. Advanced sensing and control techniques to facilitate semi-autonomous decommissioning. 1998 annual progress report

    International Nuclear Information System (INIS)

    Dawson, D.M.; Geist, R.M.; Schalkoff, R.J.

    1998-01-01

    'This research is intended to advance the technology of semi-autonomous teleoperated robotics as applied to Decontamination and Decommissioning (D and D) tasks. Specifically, research leading to a prototype dual-manipulator mobile work cell is underway. This cell is supported and enhanced by computer vision, virtual reality and advanced robotics technology. This report summarizes work after approximately 1.5 years of a 3-year project. The autonomous, non-contact creation of a virtual environment from an existing, real environment (virtualization) is an integral part of the workcell functionality. This requires that the virtual world be geometrically correct. To this end, the authors have encountered severe sensitivity in quadric estimation. As a result, alternative procedures for geometric rendering, iterative correction approaches, new calibration methods and associated hardware, and calibration quality examination software have been developed. Following geometric rendering, the authors have focused on improving the color and texture recognition components of the system. In particular, the authors have moved beyond first-order illumination modeling to include higher order diffuse effects. This allows us to combine the surface geometric information, obtained from the laser projection and surface recognition components of the system, with a stereo camera image. Low-level controllers for Puma 560 robotic arms were designed and implemented using QNX. The resulting QNX/PC based low-level robot control system is called QRobot. A high-level trajectory generator and application programming interface (API) as well as a new, flexible robot control API was required. Force/torque sensors and interface hardware have been identified and ordered. A simple 3-D OpenGL-based graphical Puma 560 robot simulator was developed and interfaced with ARCL and RCCL to assist in the development of robot motion programs.'

  14. Different impact of aspirin on renal progression in patients with predialysis advanced chronic kidney disease with or without previous stroke.

    Science.gov (United States)

    Hsiao, Kuang-Chih; Huang, Jing-Yang; Lee, Chun-Te; Hung, Tung-Wei; Liaw, Yung-Po; Chang, Horng-Rong

    2017-04-01

    The benefit of reducing the risk of stroke against increasing the risk of renal progression associated with antiplatelet therapy in patients with advanced chronic kidney disease (CKD) is controversial. We enrolled 1301 adult patients with advanced CKD treated with erythropoiesis stimulating agents from January 1, 2002 to June 30, 2009 from the 2005 Longitudinal Health Insurance Database in Taiwan. All of the patients were followed until the development of the primary or secondary endpoints, or the end of the study (December 31, 2011). The primary endpoint was the development of ischemic stroke, and the secondary endpoints included hospitalization for bleeding events, cardiovascular mortality, all-cause mortality, and renal failure. The adjusted cumulative probability of events was calculated using multivariate Cox proportional regression analysis. Adjusted survival curves showed that the usage of aspirin was not associated with ischemic stroke, hospitalization for bleeding events, cardiovascular mortality or all-cause mortality, however, it was significantly associated with renal failure. In subgroup analysis, aspirin use was associated with renal failure in the patients with no history of stroke (HR, 1.41; 95% CI, 1.14-1.73), and there was a borderline interaction between previous stroke and the use of aspirin on renal failure (interaction p=0.0565). There was no significant benefit in preventing ischemic stroke in the patients with advanced CKD who received aspirin therapy. Furthermore, the use of aspirin was associated with the risk of renal failure in the patients with advanced CKD without previous stroke. Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  15. Progressive Multifocal Leukoencephalopathy: Recent Advances and a Neuro-Ophthalmological Review.

    Science.gov (United States)

    Sudhakar, Padmaja; Bachman, David M; Mark, Alexander S; Berger, Joseph R; Kedar, Sachin

    2015-09-01

    Progressive multifocal leukoencephalopathy (PML) is a severe often fatal opportunistic infection of the central nervous system caused by reactivation of a ubiquitous polyoma virus, JC virus. Although typically characterized by multifocal asymmetric subcortical white matter lesions, it may be monofocal and affect the cortical gray matter. Among the broad spectrum of clinical manifestations that occurs with PML, visual complaints are common. Combination of representative personally observed cases of PML and comprehensive review of case series of PML from 1958 through 2014. Neuro-ophthalmic signs and symptoms were reported in approximately 20%-50% of patients with PML and can be the presenting manifestation in half of these. A majority of these presentations occur from damage to cerebral visual pathways resulting in visual field defects, cortical blindness, and other disorders of visual association. Given the decreased frequency of infratentorial and cerebellar involvement, ocular motility disorders are less common. Visual complaints occur in patients with PML and are often the presenting sign. Awareness of this condition is helpful in avoiding unnecessary delays in the diagnosis of PML and management of the underlying condition. Recent guidelines have established criteria for diagnosis of PML in the high-risk patient population and strategies to mitigate the risk in these populations.

  16. Progress In Developing an Impermeable, High Temperature Ceramic Composite for Advanced Reactor Clad And Structural Applications

    International Nuclear Information System (INIS)

    Feinroth, Herbert; Hao, Bernard; Fehrenbacher, Larry; Patterson, Mark

    2002-01-01

    Most Advanced Reactors for Energy and Space Applications require higher temperature materials for fuel cladding and core internal structures. For temperatures above 500 deg. C, metal alloys do not retain sufficient strength or long term corrosion resistance for use in either water, liquid metal or gas cooled systems. In the case of water cooled systems, such metals react exo-thermically with water during core overheating accidents, thus requiring extensive and expensive emergency systems to protect against major releases. Past efforts to apply ceramic composites (oxide, carbide or nitride based) having passive safety characteristics, good strength properties at high temperatures, and reasonable resistance to crack growth, have not been successful, either because of irradiation induced effects, or lack of impermeability to fission gases. Under a Phase 1 SBIR (Small Business Innovative Research) project sponsored by DOE's Office of Nuclear Energy, the authors have developed a new material system that may solve these problems. A hybrid tubular structure (0.6 inches in outside diameter) consisting of an inner layer of monolithic silicon carbide (SiC) and outer layers of SiC-SiC composite, bonded to the inner layer, has been fabricated in small lengths. Room temperature permeability tests demonstrate zero gas leakage at pressures up to 120 psig internal pressure. Four point flexural bending tests on these hybrid tubular specimens demonstrate a 'graceful' failure mode: i.e. - the outer composite structure sustains a failure mode under stress that is similar to the yield vs. stress characteristics of metal structures. (authors)

  17. Progress in Developing a High-Availability Advanced Tokamak Pilot Plant

    Energy Technology Data Exchange (ETDEWEB)

    Brown, T.; Goldston, R.; Kessel, C.; Neilson, G.; Menard, J.; Prager, S.; Scott, S.; Titus, P.; Zarnstorff, M., E-mail: tbrown@pppl.gov [Princeton University, Princeton Plasma Physics Laboratory, Princeton (United States); Costley, A. [Henley on Thames (United Kingdom); El-Guebaly, L. [University of Wisconsin, Madison (United States); Malang, S. [Fusion Nuclear Technology Consulting, Linkenheim (Germany); Waganer, L. [St. Louis (United States)

    2012-09-15

    Full text: A fusion pilot plant study was initiated to clarify the development needs in moving from ITER to a first of a kind fusion power plant, following a path similar to the approach adopted for the commercialization of fission. The mission of the pilot plant was set to encompass component test and fusion nuclear science missions yet produce net electricity with high availability in a device designed to be prototypical of the commercial device. The objective of the study was to evaluate three different magnetic configuration options, the advanced tokamak (AT), spherical tokamak (ST) and compact stellarator (CS) in an effort to establish component characteristics, maintenance features and the general arrangement of each candidate device. With the move to look beyond ITER the fusion community is now beginning to embark on DEMO reactor studies with an emphasis on defining configuration arrangements that can meet a high availability goal. In this paper the AT pilot plant design will be presented. The selected maintenance approach, the device arrangement and sizing of the in-vessel components and details of interfacing auxiliary systems and services that impact the ability to achieve high availability operations will be discussed. Efforts made to enhance the interaction of in-vessel maintenance activities, the hot cell and the transfer process to develop simplifying solutions will also be addressed. (author)

  18. Advances in Wilms Tumor Treatment and Biology: Progress Through International Collaboration.

    Science.gov (United States)

    Dome, Jeffrey S; Graf, Norbert; Geller, James I; Fernandez, Conrad V; Mullen, Elizabeth A; Spreafico, Filippo; Van den Heuvel-Eibrink, Marry; Pritchard-Jones, Kathy

    2015-09-20

    Clinical trials in Wilms tumor (WT) have resulted in overall survival rates of greater than 90%. This achievement is especially remarkable because improvements in disease-specific survival have occurred concurrently with a reduction of therapy for large patient subgroups. However, the outcomes for certain patient subgroups, including those with unfavorable histologic and molecular features, bilateral disease, and recurrent disease, remain well below the benchmark survival rate of 90%. Therapy for WT has been advanced in part by an increasingly complex risk-stratification system based on patient age; tumor stage, histology, and volume; response to chemotherapy; and loss of heterozygosity at chromosomes 1p and 16q. A consequence of this system has been the apportionment of patients into such small subgroups that only collaboration between large international WT study groups will support clinical trials that are sufficiently powered to answer challenging questions that move the field forward. This article gives an overview of the Children's Oncology Group and International Society of Pediatric Oncology approaches to WT and focuses on four subgroups (stage IV, initially inoperable, bilateral, and relapsed WT) for which international collaboration is pressing. In addition, biologic insights resulting from collaborative laboratory research are discussed. A coordinated expansion of international collaboration in both clinical trials and laboratory science will provide real opportunity to improve the treatment and outcomes for children with renal tumors on a global level. © 2015 by American Society of Clinical Oncology.

  19. Recent Progress in Advanced Nanobiological Materials for Energy and Environmental Applications

    Directory of Open Access Journals (Sweden)

    Hyo-Jick Choi

    2013-12-01

    Full Text Available In this review, we briefly introduce our efforts to reconstruct cellular life processes by mimicking natural systems and the applications of these systems to energy and environmental problems. Functional units of in vitro cellular life processes are based on the fabrication of artificial organelles using protein-incorporated polymersomes and the creation of bioreactors. This concept of an artificial organelle originates from the first synthesis of poly(siloxane-poly(alkyloxazoline block copolymers three decades ago and the first demonstration of protein activity in the polymer membrane a decade ago. The increased value of biomimetic polymers results from many research efforts to find new applications such as functionally active membranes and a biochemical-producing polymersome. At the same time, foam research has advanced to the point that biomolecules can be efficiently produced in the aqueous channels of foam. Ongoing research includes replication of complex biological processes, such as an artificial Calvin cycle for application in biofuel and specialty chemical production, and carbon dioxide sequestration. We believe that the development of optimally designed biomimetic polymers and stable/biocompatible bioreactors would contribute to the realization of the benefits of biomimetic systems. Thus, this paper seeks to review previous research efforts, examine current knowledge/key technical parameters, and identify technical challenges ahead.

  20. Benefit-Risk Summary of Regorafenib for the Treatment of Patients with Advanced Hepatocellular Carcinoma That Has Progressed on Sorafenib.

    Science.gov (United States)

    Pelosof, Lorraine; Lemery, Steven; Casak, Sandra; Jiang, Xiaoping; Rodriguez, Lisa; Pierre, Vadryn; Bi, Youwei; Liu, Jiang; Zirkelbach, Jeanne Fourie; Patel, Anuja; Goldberg, Kirsten B; McKee, Amy E; Keegan, Patricia; Pazdur, Richard

    2018-04-01

    On April 27, 2017, the U.S. Food and Drug Administration approved regorafenib for the treatment of patients with advanced hepatocellular carcinoma (HCC) who had previously been treated with sorafenib. Approval was based on the results of a single, randomized, placebo-controlled trial (RESORCE) that demonstrated an improvement in overall survival (OS). Patients were randomly allocated to receive regorafenib160 mg orally once daily or matching placebo for the first 21 days of each 28-day cycle. The trial demonstrated a significant improvement in OS (hazard ratio [HR] = 0.63; 95% confidence interval [CI], 0.50-0.79, p  regorafenib arm and 7.8 months in the placebo arm. A statistically significant improvement in progression-free survival (PFS) based on modified RECIST for HCC [Semin Liver Dis 2010;30:52-60] (HR = 0.46; 95% CI, 0.37-0.56, p  regorafenib and placebo arms, respectively. The overall response rate, based on modified RECIST for HCC, was 11% in the regorafenib arm and 4% in the placebo arm. The toxicity profile was consistent with that observed in other indications; the most clinically significant adverse reactions were palmar-plantar erythrodysesthesia, diarrhea, and hypertension. Based on the improvement in survival and acceptable toxicity, a favorable benefit-to-risk evaluation led to approval for treatment of patients with advanced HCC. Regorafenib is the first drug approved by the U.S. Food and Drug Administration for the treatment of hepatocellular carcinoma that has progressed on sorafenib and is expected to become a standard of care for these patients. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.

  1. A Randomized Controlled Trial of a Cardiopulmonary Resuscitation Video in Advance Care Planning for Progressive Pancreas and Hepatobiliary Cancer Patients

    Science.gov (United States)

    Volandes, Angelo E.; Chen, Ling Y.; Gary, Kristen A.; Li, Yuelin; Agre, Patricia; Levin, Tomer T.; Reidy, Diane L.; Meng, Raymond D.; Segal, Neil H.; Yu, Kenneth H.; Abou-Alfa, Ghassan K.; Janjigian, Yelena Y.; Kelsen, David P.; O'Reilly, Eileen M.

    2013-01-01

    Abstract Background Cardiopulmonary resuscitation (CPR) is an important advance directive (AD) topic in patients with progressive cancer; however such discussions are challenging. Objective This study investigates whether video educational information about CPR engenders broader advance care planning (ACP) discourse. Methods Patients with progressive pancreas or hepatobiliary cancer were randomized to an educational CPR video or a similar CPR narrative. The primary end-point was the difference in ACP documentation one month posttest between arms. Secondary end-points included study impressions; pre- and post-intervention knowledge of and preferences for CPR and mechanical ventilation; and longitudinal patient outcomes. Results Fifty-six subjects were consented and analyzed. Rates of ACP documentation (either formal ADs or documented discussions) were 40% in the video arm (12/30) compared to 15% in the narrative arm (4/26), OR=3.6 [95% CI: 0.9–18.0], p=0.07. Post-intervention knowledge was higher in both arms. Posttest, preferences for CPR had changed in the video arm but not in the narrative arm. Preferences regarding mechanical ventilation did not change in either arm. The majority of subjects in both arms reported the information as helpful and comfortable to discuss, and they recommended it to others. More deaths occurred in the video arm compared to the narrative arm, and more subjects died in hospice settings in the video arm. Conclusions This pilot randomized trial addressing downstream ACP effects of video versus narrative decision tools demonstrated a trend towards more ACP documentation in video subjects. This trend, as well as other video effects, is the subject of ongoing study. PMID:23725233

  2. Advanced thermally stable jet fuels: Technical progress report, October 1994--December 1994

    Energy Technology Data Exchange (ETDEWEB)

    Schobert, H.H.; Eser, S.; Song, C.; Hatcher, P.G.; Boehman, A.; Coleman, M.M.

    1995-02-01

    There are five tasks within this project on thermally stable coal-based jet fuels. Progress on each of the tasks is described. Task 1, Investigation of the quantitative degradation chemistry of fuels, has 5 subtasks which are described: Literature review on thermal stability of jet fuels; Pyrolytic and catalytic reactions of potential endothermic fuels: cis- and trans-decalin; Use of site specific {sup 13}C-labeling to examine the thermal stressing of 1-phenylhexane: A case study for the determination of reaction kinetics in complex fuel mixtures versus model compound studies; Estimation of critical temperatures of jet fuels; and Surface effects on deposit formation in a flow reactor system. Under Task 2, Investigation of incipient deposition, the subtask reported is Uncertainty analysis on growth and deposition of particles during heating of coal-derived aviation gas turbine fuels; under Task 3, Characterization of solid gums, sediments, and carbonaceous deposits, is subtask, Studies of surface chemistry of PX-21 activated carbon during thermal degradation of jet A-1 fuel and n-dodecane; under Task 4, Coal-based fuel stabilization studies, is subtask, Exploratory screening and development potential of jet fuel thermal stabilizers over 400 C; and under Task 5, Exploratory studies on the direct conversion of coal to high quality jet fuels, are 4 subtasks: Novel approaches to low-severity coal liquefaction and coal/resid co-processing using water and dispersed catalysts; Shape-selective naphthalene hydrogenation for production of thermally stable jet fuels; Design of a batch mode and a continuous mode three-phase reactor system for the liquefaction of coal and upgrading of coal liquids; and Exploratory studies on coal liquids upgrading using mesopores molecular sieve catalysts. 136 refs., 69 figs., 24 tabs.

  3. Premature ovarian failure

    Directory of Open Access Journals (Sweden)

    Persani Luca

    2006-04-01

    Full Text Available Abstract Premature ovarian failure (POF is a primary ovarian defect characterized by absent menarche (primary amenorrhea or premature depletion of ovarian follicles before the age of 40 years (secondary amenorrhea. It is a heterogeneous disorder affecting approximately 1% of women e.g. Turner syndrome represent the major cause of primary amenorrhea associated with ovarian dysgenesis. Despite the description of several candidate genes, the cause of POF remains undetermined in the vast majority of the cases. Management includes substitution of the hormone defect by estrogen/progestin preparations. The only solution presently available for the fertility defect in women with absent follicular reserve is ovum donation.

  4. Advanced research and technology development fossil energy materials program. Quarterly progress report for the period ending September 30, 1981

    Energy Technology Data Exchange (ETDEWEB)

    Bradley, R.A. (comp.)

    1981-12-01

    This is the fourth combined quarterly progress report for those projects that are part of the Advanced Research and Technology Development Fossil Energy Materials Program. The objective is to conduct a program of research and development on materials for fossil energy applications with a focus on the longer-term and generic needs of the various fossil fuel technologies. The program includes research aimed toward a better understanding of materials behavior in fossil energy environments and the development of new materials capable of substantial enhancement of plant operations and reliability. Work performed on the program generally falls into the Applied Research and Exploratory Development categories as defined in the DOE Technology Base Review, although basic research and engineering development are also conducted. A substantial portion of the work on the AR and TD Fossil Energy Materials Program is performed by participating cntractor organizations. All subcontractor work is monitored by Program staff members at ORNL and Argonne National Laboratory. This report is organized in accordance with a work breakdown structure defined in the AR and TD Fossil Energy Materials Program Plan for FY 1981 in which projects are organized according to fossil energy technologies. We hope this series of AR and TD Fossil Energy Materials Program quarterly progress reports will aid in the dissemination of information developed on the program.

  5. Advanced-ORIENT cycle, its scientific progress and prospect for engineering feasibility

    International Nuclear Information System (INIS)

    Koyama, Shin-ichi; Yamagishi, Isao; Fujii, Yasuhiko; Suzuki, Tatsuya; Ozawa, Masaki; Fujita, Reiko; Okada, Ken; Tatenuma, Katsuyoshi; Mimura, Hitoshi

    2011-01-01

    For the ultimate minimization of the ecological risks originated in nuclear fuel recycling, a new fuel cycle paradigm was proposed and the basic researches have been carried out as a first phase under the Adv.-ORIENT (Advanced Optimization by Recycling Instructive Elements) Cycle project. In this paradigm, effective separation of actinide (An) and long lived-fission product (LLFP), transmutation of An, utilization of separated nuclides, such as lanthanides (Lns) and platinum group metals (PGM), were the main directions. In such directions, tertiary pyridine-type resin (TPR) enabled to separate minor actinide (MA)/Ln and then Am/Cm precisely from spent fuel, provided permitting to use HCl as well as and HNO 3 media. Recovery of very pure Am and Cm products could be done in this phase. The PGM and Tc separation; Catalytic electrolytic extraction (CEE) method could effectively separate the light PGM ,Tc from HCl and HNO 3 media, especially by HCl media. The PGM and Tc utilization; Mixed deposit obtained from the CEE experiments, Ru/Rh/Pd/Tc(Re)-Pt electrodes indicated the highest catalytic reactivity on electrolytic production of hydrogen in an alkali solution. Recovery of Cs from simulated spent fuel solution by silica gel loaded with ammonium molybdophosphate (AMP) was carried out, and the uptake rate achieved more than 90%. Separated Cs is expected to utilize as a heat source element. As basic engineering research efforts, some candidate metals, such as Ta, Nb, Zr and Hastelloy-B (Ni-28Mo), were examined to confirm an anti-corrosive property in wide HCl environment. Gram scale experiment to identify a thermo-chemical stability of TPR and TBP (as a reference) was also performed experimentally, and process safety conditions could be found out for its practical use. In this paper, study for each integrant technology was concluded as first trial of Adv.-ORIENT Cycle project, and the perspective for next phase was proposed. (author)

  6. Advanced thermally stable jet fuels. Technical progress report, April 1993--June 1993

    Energy Technology Data Exchange (ETDEWEB)

    Schobert, H.H.; Eser, S.; Song, C. [and others

    1993-10-01

    The Penn State program in advanced thermally stable coal-based jet fuels has five broad objectives: (1) development of mechanisms of degradation and solids formation; (2) quantitative measurement of growth of sub-micrometer and micrometer-sized particles suspended in fuels during thermal stressing; (3) characterization of carbonaceous deposits by various instrumental and microscopic methods; (4) elucidation of the role of additives in retarding the formation of carbonaceous solids; and (5) assessment of the potential of production of high yields of cycloalkanes by direct liquefaction of coal. Some of our accomplishments and findings are: The product distribution and reaction mechanisms for pyrolysis of alkylcyclohexanes at 450{degree}C have been investigated in detail. In this report we present results of pyrolysis of cyclohexane and a variety of alkylcyclohexanes in nitrogen atmospheres, along with pseudo-first order rate constants, and possible reaction mechanisms for the origin of major pyrolysis products are presented. Addition of PX-21 activated carbon effectively stops the formation of carbonaceous solids on reactor walls during thermal stressing of JPTS. A review of physical and chemical interactions in supercritical fluids has been completed. Work has begun on thermal stability studies of a second generation of fuel additives, 1,2,3,4-tetrahydro-l-naphthol, 9,10-phenanthrenediol, phthalan, and 1,2-benzenedimethanol, and with careful selection of the feedstock, it is possible to achieve 85--95% conversion of coal to liquids, with 40--50% of the dichloromethane-soluble products being naphthalenes. (Further hydrogenation of the naphthalenes should produce the desired highly stable decalins.)

  7. Plasma miR-200b in ovarian carcinoma patients: distinct pattern of pre/post-treatment variation compared to CA-125 and potential for prediction of progression-free survival.

    Science.gov (United States)

    Kapetanakis, Nikiforos-Ioannis; Uzan, Catherine; Jimenez-Pailhes, Anne-Sophie; Gouy, Sébastien; Bentivegna, Enrica; Morice, Philippe; Caron, Olivier; Gourzones-Dmitriev, Claire; Le Teuff, Gwénaël; Busson, Pierre

    2015-11-03

    Ovarian carcinomas (OvCa) are highly heterogeneous malignancies. We investigated four circulating plasma microRNAs (miR-21, miR-34a, miR-200b and miR-205) as candidate biomarkers. Using qPCR, we assessed the plasma concentration of these markers in 101 women, including 51 previously untreated OvCa patients, 25 healthy women and 25 patients bearing benign pelvic lesions. For a subset of 33 OvCa patients, the assay was repeated at the end of the primary treatment. The pattern of variations (post- minus pre-treatment) of concentration was compared to that of CA-125. A Cox regression model was used to study the association between variations and the progression-free survival (PFS). Plasma miR-200b proved to have a greater average concentration in OvCa samples (median 2-ΔΔCt = 15.18) than in samples linked to non-malignant lesions (median 2-ΔΔCt = 1.26, p-value = 0.0004). Its concentration was highly heterogeneous among OvCa patients, without any correlations with the FIGO stage and the pre-treatment CA-125 level. The decrease in CA-125 concentration was constant and often dramatic, while the variations of miR-200b concentration were much more diverse. The variation of miR-200b was marginally associated with the PFS (hazard ratio=2.95 95%CI=[0.94; 9.28], p=0.06) while miR-200b as a continuous time-dependent variable was significantly associated (HR=1.06 [1.02; 1.10], p=0.003). This study is the first direct empirical evidence that miR-200b can provide additional information, independent of CA-125 in OvCa patients.

  8. Cost-effectiveness of Paclitaxel + Ramucirumab Combination Therapy for Advanced Gastric Cancer Progressing After First-line Chemotherapy in Japan.

    Science.gov (United States)

    Saito, Shota; Muneoka, Yusuke; Ishikawa, Takashi; Akazawa, Kouhei

    2017-12-01

    The combination of paclitaxel + ramucirumab is a standard second-line treatment in patients with advanced gastric cancer. This therapy has been associated with increased median overall survival and progression-free survival compared with those with paclitaxel monotherapy. We evaluated the cost-effectiveness of paclitaxel + ramucirumab combination therapy in patients with advanced gastric cancer, from the perspective of health care payers in Japan. We constructed a Markov model to compare, over a time horizon of 3 years, the costs and effectiveness of the combination of paclitaxel + ramucirumab and paclitaxel alone as second-line therapies for advanced gastric cancer in Japan. Health outcomes were measured in life-years (LYs) and quality-adjusted (QA) LYs gained. Costs were calculated using year-2016 Japanese yen (¥1 = US $17.79) according to the social insurance reimbursement schedule and drug tariff of the fee-for-service system in Japan. Model robustness was addressed through 1-way and probabilistic sensitivity analyses. The costs and QALYs were discounted at a rate of 2% per year. The willingness-to-pay threshold was set at the World Health Organization's criterion of ¥12 million, because no consensus exists regarding the threshold for acceptable cost per QALY ratios in Japan's health policy. Paclitaxel + ramucirumab combination therapy was estimated to provide an additional 0.09 QALYs (0.10 LYs) at a cost of ¥3,870,077, resulting in an incremental cost-effectiveness ratio of ¥43,010,248/QALY. The incremental cost-effectiveness ratio for the combination therapy was >¥12 million/QALY in all of the 1-way and probabilistic sensitivity analyses. Adding ramucirumab to a regimen of paclitaxel in the second-line treatment of advanced gastric cancer is expected to provide a minimal incremental benefit at a high incremental cost per QALY. Based on our findings, adjustments in the price of ramucirumab, as well as improves in other clinical parameters such as survival

  9. Overview of JT-60U progress towards steady-state advanced tokamak

    International Nuclear Information System (INIS)

    Ide, S.

    2005-01-01

    Recent experimental results on steady state advanced tokamak (AT) research on JT-60U are presented with emphasis on longer time scale in comparison with characteristics time scales in plasmas. Towards this, modification on control in operation, heating and diagnostics systems have been done. As the results, ∼ 60 s I p flat top and an ∼ 30 s H-mode are obtained. The long pulse modification has opened a door into a new domain for JT-60U. The high normalized beta (β N ) of 2.3 is maintained for 22.3 s and 2.5 for 16.5 s in a high β p H-mode plasma. A standard ELMy H-mode plasma is also extended and change in wall recycling in such a longer time scale has been unveiled. Development and investigation of plasmas relevant to AT operation has been continued in former 15 s discharges as well in which higherNB power (≤ 10 s) is available. Higher β N ∼ 3 is maintained for 6.2 s in high β p H-mode plasmas. High bootstrap current fraction (f BS ) of ∼ 75% is sustained for 7.4 s in an RS plasma. On NTM suppression by localized ECCD, ECRF injection preceding the mode saturation is found to be more effective to suppress the mode with less power compared to the injection after the mode saturated. The domain of the NTM suppression experiments is extended to the high β N regime, and effectiveness of m/n=3/2 mode suppression by ECCD is demonstrated at β N ∼ 2.5-3. Genuine center-solenoid less tokamak plasma start up is demonstrated. In a current hole region, it is shown that no scheme drives a current in any direction. Detailed measurement in both spatial and energy spaces of energetic ions showed dynamic change in the energetic ion profile at collective instabilities. Impact of toroidal plasma rotation on ELM behaviors is clarified in grassy ELM and QH domains. (author)

  10. WNT7A/?-catenin signaling induces FGF1 and influences sensitivity to niclosamide in ovarian cancer

    OpenAIRE

    King, Mandy L.; Lindberg, Mallory E.; Stodden, Genna R.; Okuda, Hiroshi; Ebers, Steven D.; Johnson, Alyssa; Montag, Anthony; Lengyel, Ernst; MacLean, James A.; Hayashi, Kanako

    2014-01-01

    We previously characterized the link between WNT7A and the progression of ovarian cancer. Other groups have identified FGF1 as a relevant risk factor in ovarian cancer. Here, we show a linkage between these two signaling pathways that may be exploited to improve treatment and prognosis of patients with ovarian cancer. High expression of WNT7A and FGF1 are correlated in ovarian carcinomas and poor overall patient survival. A chromatin immunoprecipitation assay demonstrated that WNT7A/?-catenin...

  11. Laser treatment of drusen to prevent progression to advanced age-related macular degeneration.

    Science.gov (United States)

    Virgili, Gianni; Michelessi, Manuele; Parodi, Maurizio B; Bacherini, Daniela; Evans, Jennifer R

    2015-10-23

    Drusen are amorphous yellowish deposits beneath the sensory retina. People with drusen, particularly large drusen, are at higher risk of developing age-related macular degeneration (AMD). The most common complication in AMD is choroidal neovascularisation (CNV), the growth of new blood vessels in the centre of the macula. The risk of CNV is higher among people who are already affected by CNV in one eye.It has been observed clinically that laser photocoagulation of drusen leads to their disappearance and may prevent the occurrence of advanced disease (CNV or geographic atrophy) associated with visual loss. To examine the effectiveness and adverse effects of laser photocoagulation of drusen in AMD. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2015, Issue 7), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to August 2015), EMBASE (January 1980 to August 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to August 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 3 August 2015. Randomised controlled trials (RCTs) of laser treatment of drusen in AMD in which laser treatment had been compared with no intervention or sham treatment. Two types of trials were included. Some trials studied one eye of each participant (unilateral studies); other studies recruited participants with bilateral drusen and randomised one eye to photocoagulation or control and the fellow eye to the other group. Two review authors independently selected studies and extracted data. We pooled data from unilateral and bilateral

  12. [Screening of ovarian cancer : not for tomorrow].

    Science.gov (United States)

    Vuilleumier, Aurélie; Labidi-Galy, Intidhar

    2017-05-17

    As the worldwide incidence of cancer continuously rises, one of the measures to reduce mortality is early diagnosis while the disease is still curable. Colonoscopy screening and PAP-smears are worthwhile examples illustrating the impact of early diagnosis on mortality. Ovarian cancer is the first cause of mortality by gynecological cancers in Switzerland (incidence of 600 new cases / year), mostly diagnosed at advanced stages with a poor prognosis. Could surveillance measures improve survival ? Three large-scale randomized control trials failed to show mortality reduction from ovarian cancer with the methods currently available. A better comprehension of pathogenesis can allow the development of new strategies of screening.

  13. Cancer stem-like cells of ovarian clear cell carcinoma are enriched in the ALDH-high population associated with an accelerated scavenging system in reactive oxygen species.

    Science.gov (United States)

    Mizuno, T; Suzuki, N; Makino, H; Furui, T; Morii, E; Aoki, H; Kunisada, T; Yano, M; Kuji, S; Hirashima, Y; Arakawa, A; Nishio, S; Ushijima, K; Ito, K; Itani, Y; Morishige, K

    2015-05-01

    In ovarian cancer cases, recurrence after chemotherapy is frequently observed, suggesting the involvement of ovarian cancer stem-like cells (CSCs). The chemoresistance of ovarian clear cell carcinomas is particularly strong in comparison to other epithelial ovarian cancer subtypes. We investigated the relationship between a CSC marker, aldehyde dehydrogenase 1 (ALDH1), and clinical prognosis using ovarian clear cell carcinoma tissue samples. Furthermore, we investigated the antioxidant mechanism by which CSCs maintain a lower reactive oxygen species (ROS) level, which provides protection from chemotherapeutic agents. Immunohistochemical staining was performed to examine the CSC markers (CD133, CD44, ALDH1) using ovarian clear cell carcinoma tissue samples (n=81). Clear cell carcinoma cell lines (KOC-7C, OVTOKO) are separated into the ALDH-high and ALDH-low populations by ALDEFLUOR assay and fluorescence-activated cell sorting (FACS). We compared the intracellular ROS level, mRNA level of the antioxidant enzymes and Nrf2 expression of the two populations. High ALDH1 expression levels are related to advanced stage in clear cell carcinoma cases. ALDH1 expression significantly reduced progression free survival. Other markers are not related to clinical stage and prognosis. ALDH-high cells contained a lower ROS level than ALDH-low cells. Antioxidant enzymes were upregulated in ALDH-high cells. ALDH-high cells showed increased expression of Nrf2, a key transcriptional factor of the antioxidant system. ALDH-positive CSCs might have increased Nrf2-induced antioxidant scavengers, which lower ROS level relevant to chemoresistance in ovarian clear cell carcinoma. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Intraperitoneal chemotherapy for advanced ovarian and peritoneal cancers in patients following interval debulking surgery or primary cytoreductive surgery: Tom Baker Cancer Centre experience from 2006 to 2009.

    Science.gov (United States)

    Nelson, Gregory; Lucero, Carlos Aspe; Chu, Pamela; Nation, Jill; Ghatage, Prafull

    2010-03-01

    To describe our experience with cisplatin- and paclitaxel-based IP chemotherapy in patients treated initially with either neoadjuvant chemotherapy and interval debulking surgery (IDS) or primary cytoreductive surgery (PCRS). We performed a retrospective review of the records of 67 patients (38 IDS, 29 PCRS) enrolled in the intraperitoneal (IP) chemotherapy program at the Tom Baker Cancer Centre between 2006 and 2009. Information pertaining to patient demographics, IP chemotherapy toxicity, and catheter complications was extracted, and the median time to recurrence was calculated. Most patients in the study were aged 50 to 70 years and had a diagnosis of stage III serous ovarian cancer. Overall, 295/393 IP cycles (75%) were successfully administered. The proportion of patients completing six cycles of chemotherapy in the IDS and PCRS groups was 53% and 59%, respectively. Frequent (> 25%) Grade 1 to 2 chemotherapy toxicities included fatigue, peripheral neuropathy, and nausea. Catheter complications were observed in 34% of patients (23/67). The recurrence rates for patients completing four or more cycles of IP chemotherapy in the IDS and PCRS groups were 58% and 35%, respectively, with the median time to recurrence approximately one year. Although IP chemotherapy is well tolerated in both IDS and PCRS patients, the median time to recurrence is shorter than expected.

  15. Ectopic ovarian pregnancy

    International Nuclear Information System (INIS)

    Sachdev, P.S.; Jatoi, N.; Memon, R.A.; Sachdev, C.S.

    2003-01-01

    A case of ectopic ovarian pregnancy is presented occurring in a 24 years old woman after natural conception. The clinical diagnosis was ruptured tubal pregnancy. Gross findings were suggestive of ruptured corpus luteum cyst on exploration. The histopathological examination of specimen brought forward the diagnosis of ovarian pregnancy. (author)

  16. Ablation of an Ovarian Tumor Family Deubiquitinase Exposes the Underlying Regulation Governing the Plasticity of Cell Cycle Progression in Toxoplasma gondii.

    Science.gov (United States)

    Dhara, Animesh; de Paula Baptista, Rodrigo; Kissinger, Jessica C; Snow, E Charles; Sinai, Anthony P

    2017-11-21

    The Toxoplasma genome encodes the capacity for distinct architectures underlying cell cycle progression in a life cycle stage-dependent manner. Replication in intermediate hosts occurs by endodyogeny, whereas a hybrid of schizogony and endopolygeny occurs in the gut of the definitive feline host. Here, we characterize the consequence of the loss of a cell cycle-regulated o varian tu mor (OTU family) deubiquitinase, OTUD3A of Toxoplasma gondii (TgOTUD3A; TGGT1_258780), in T. gondii tachyzoites. Rather than the mutation being detrimental, mutant parasites exhibited a fitness advantage, outcompeting the wild type. This phenotype was due to roughly one-third of TgOTUD3A-knockout (TgOTUD3A-KO) tachyzoites exhibiting deviations from endodyogeny by employing replication strategies that produced 3, 4, or 5 viable progeny within a gravid mother instead of the usual 2. We established the mechanistic basis underlying these altered replication strategies to be a dysregulation of centrosome duplication, causing a transient loss of stoichiometry between the inner and outer cores that resulted in a failure to terminate S phase at the attainment of 2N ploidy and/or the decoupling of mitosis and cytokinesis. The resulting dysregulation manifested as deviations in the normal transitions from S phase to mitosis (S/M) (endopolygeny-like) or M phase to cytokinesis (M/C) (schizogony-like). Notably, these imbalances are corrected prior to cytokinesis, resulting in the generation of normal progeny. Our findings suggest that decisions regarding the utilization of specific cell cycle architectures are controlled by a ubiquitin-mediated mechanism that is dependent on the absolute threshold levels of an as-yet-unknown target(s). Analysis of the TgOTUD3A-KO mutant provides new insights into mechanisms underlying the plasticity of apicomplexan cell cycle architecture. IMPORTANCE Replication by Toxoplasma gondii can occur by 3 distinct cell cycle architectures. Endodyogeny is used by asexual

  17. The immunohistochemical expression of endocrine gland-derived-VEGF (EG-VEGF) as a prognostic marker in ovarian cancer.

    Science.gov (United States)

    Bălu, Sevilla; Pirtea, L; Gaje, Puşa; Cîmpean, Anca Maria; Raica, M

    2012-01-01

    Ovarian cancer-related angiogenesis is a complex process orchestrated by many positive and negative regulators. Many growth factors are involved in the development of the tumor-associated vasculature, and from these, endocrine gland-derived vascular endothelial growth factor (EG-VEGF) seems to play a crucial role. EG-VEGF is the first organ-specific angiogenic factor and its effects are restricted to the endothelial cells of the endocrine glands. Although EG-VEGF was detected in both normal and neoplastic ovaries, its clinical significance remains controversial. In the present study, we analyzed 30 patients with epithelial ovarian cancer, and the immunohistochemical expression of EG-VEGF was compared with the conventional clinico-pathological parameters of prognosis. Neoplastic cells of the ovarian carcinoma expressed EG-VEGF in 73.33% of the cases, as a cytoplasmic granular product of reaction. We found a strong correlation between the expression of EG-VEGF at protein level and tumor stage, grade, and microscopic type. The expression of EG-VEGF was found in patients with stage III and IV, but not in stage II. The majority of serous adenocarcinoma, half of the cases with clear cell carcinoma and two cases with endometrioid carcinoma showed definite expression in tumor cells. No positive reaction was found in the cases with mucinous carcinoma. Our results showed that EG-VEGF expression is an indicator not only of the advanced stage, but also of ovarian cancer progression. Based on these data, we concluded that EG-VEGF expression in tumor cells of the epithelial ovarian cancer is a good marker of unfavorable prognosis and could be an attractive therapeutic target in patients with advanced-stage tumors, refractory conventional chemotherapy.

  18. Autoimmune premature ovarian failure

    Directory of Open Access Journals (Sweden)

    Beata Komorowska

    2017-02-01

    Full Text Available Premature ovarian failure (POF, also termed as primary ovarian insufficiency (POI, is a highly heterogenous condition affecting 0.5-3.0% of women in childbearing age. These young women comprise quite a formidable group with unique physical and psychological needs that require special attention. Premature ovarian senescence (POS in all of its forms evolves insidiously as a basically asymptomatic process, leading to complete loss of ovarian function, and POI/POF diagnoses are currently made at relatively late stages. Well-known and well-documented risk factors exist, and the presence or suspicion of autoimmune disorder should be regarded as an important one. Premature ovarian failure is to some degree predictable in its occurrence and should be considered while encountering young women with loss of menstrual regularity, especially when there is a concomitant dysfunction in the immune system.

  19. Prevention of ovarian cancer.

    Science.gov (United States)

    Hanna, Louise; Adams, Malcolm

    2006-04-01

    Ovarian cancer is the leading cause of death from gynaecological malignancy. The incidence is high in the Western world. The incidence of ovarian cancer is reduced by pregnancy, lactation, the oral contraceptive pill and tubal ligation. Lifestyle factors are important in the aetiology of ovarian cancer and current evidence suggests the risk can be reduced by eating a diet rich in fruit and vegetables, taking regular exercise, avoiding smoking, avoiding being overweight and avoiding long-term use of hormonal replacement therapy (HRT). Familial ovarian cancer is responsible for about 10% of ovarian cancer cases. Strategies available to high-risk women include screening (covered elsewhere) and prophylactic salpingo-oophorectomy. The precise role of chemoprevention for high-risk women in the form of the oral contraceptive pill is unclear.

  20. 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

  1. Ovarian cancer-related hypophosphatemic osteomalacia--a case report.

    Science.gov (United States)

    Lin, Hung-An; Shih, Shyang-Rong; Tseng, Yu-Ting; Chen, Chi-Hau; Chiu, Wei-Yih; Hsu, Chih-Yao; Tsai, Keh-Sung

    2014-12-01

    Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused primarily by benign mesenchymal tumors. It has been associated with malignancies in rare cases. High serum levels of fibroblast growth factor (FGF) 23 reported in a group of patients with ovarian cancer had normal serum phosphate levels. There had been no ovarian cancer-related hypophosphatemic osteomalacia in a search of the literature. We investigated a 57-year-old woman with progressive low back pain. Clinical, biochemical, and radiological assessments were performed. The patient's serum phosphate and FGF23 levels were evaluated at baseline and after treatment for ovarian cancer. The patient presented with progressive low back pain and weight loss during the previous 6 months. Imaging studies revealed low bone mineral density and multiple suspicious spinal metastatic lesions. Laboratory examination showed hypophosphatemia, hyperphosphaturia, normocalcemia, an elevated serum alkaline phosphatase level, and an elevated serum FGF23 level. Because TIO was suspected, a tumor survey was performed, and ovarian carcinoma with multiple metastasis was detected. After surgery and chemotherapy treatments for ovarian cancer, the serum phosphate and FGF23 levels returned to normal, and the low back pain improved. To our knowledge, this is the first case of ovarian cancer-related hypophosphatemic osteomalacia reported in the literature. TIO should be considered in patients with ovarian cancer presenting with weakness, bone pain, and fractures. Investigation of TIO is appropriate when these patients present hypophosphatemia.

  2. Ovarian Cancer-Related Hypophosphatemic Osteomalacia—A Case Report

    Science.gov (United States)

    Lin, Hung-An; Shih, Shyang-Rong; Tseng, Yu-Ting; Chen, Chi-Hau; Chiu, Wei-Yih; Hsu, Chih-Yao

    2014-01-01

    Context: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused primarily by benign mesenchymal tumors. It has been associated with malignancies in rare cases. High serum levels of fibroblast growth factor (FGF) 23 reported in a group of patients with ovarian cancer had normal serum phosphate levels. There had been no ovarian cancer-related hypophosphatemic osteomalacia in a search of the literature. Objective: We investigated a 57-year-old woman with progressive low back pain. Design and Intervention: Clinical, biochemical, and radiological assessments were performed. The patient's serum phosphate and FGF23 levels were evaluated at baseline and after treatment for ovarian cancer. Results: The patient presented with progressive low back pain and weight loss during the previous 6 months. Imaging studies revealed low bone mineral density and multiple suspicious spinal metastatic lesions. Laboratory examination showed hypophosphatemia, hyperphosphaturia, normocalcemia, an elevated serum alkaline phosphatase level, and an elevated serum FGF23 level. Because TIO was suspected, a tumor survey was performed, and ovarian carcinoma with multiple metastasis was detected. After surgery and chemotherapy treatments for ovarian cancer, the serum phosphate and FGF23 levels returned to normal, and the low back pain improved. Conclusions: To our knowledge, this is the first case of ovarian cancer-related hypophosphatemic osteomalacia reported in the literature. TIO should be considered in patients with ovarian cancer presenting with weakness, bone pain, and fractures. Investigation of TIO is appropriate when these patients present hypophosphatemia. PMID:25181387

  3. Characterization of the Chicken Ovarian Cancer Model

    National Research Council Canada - National Science Library

    Rodriguez, Gustavo

    2002-01-01

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

  4. Characterization of the Chicken Ovarian Cancer Model

    National Research Council Canada - National Science Library

    Rodriguez, Gustavo C

    2004-01-01

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

  5. Characterization of the Chicken Ovarian Cancer Model

    National Research Council Canada - National Science Library

    Rodriguez, Gustavo C

    2005-01-01

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

  6. Characterization of the Chicken Ovarian Cancer Model

    National Research Council Canada - National Science Library

    Rodriguez, Gustavo

    2003-01-01

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

  7. Characterization of the Chicken Ovarian Cancer Model

    National Research Council Canada - National Science Library

    Rodriquez, Gustavo

    2001-01-01

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

  8. Laparoscopic-assisted extracorporeal ovarian cystectomy: a new technique.

    Science.gov (United States)

    Ikuma, Kenichino; Amin, Magdy; Yukio, Yamada; Hisato, Okuo; Yoshihiro, Ito; Shintaro, Ueda; Masako, Tanaka; Yasuki, Koyasu

    2004-01-01

    An increasing number of adnexal masses are currently managed laparoscopically, which has hampered progress regarding the different techniques of laparoscopic surgery. In this chapter, a modified application of surgical instrument was described in laparoscopic ovarian cystectomy-we named this device, Lap-Disc Mini. This new instrument has three rings, an inner flexible ring fixed to a middle ring by a rubber corset, and an additional dynamic outer ring that has a rubbery-like iris opening, which allows the application of different-sized trocars and extracorporeal ovarian cystectomy. This technique has proved to be effective and safe, especially in removing large ovarian cyst.

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

    Science.gov (United States)

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

    2015-12-01

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

  10. A mild ovarian stimulation strategy in women with poor ovarian reserve undergoing IVF: a multicenter randomized non-inferiority trial.

    Science.gov (United States)

    Youssef, M A; van Wely, M; Al-Inany, H; Madani, T; Jahangiri, N; Khodabakhshi, S; Alhalabi, M; Akhondi, M; Ansaripour, S; Tokhmechy, R; Zarandi, L; Rizk, A; El-Mohamedy, M; Shaeer, E; Khattab, M; Mochtar, M H; van der Veen, F

    2017-01-01

    In subfertile women with poor ovarian reserve undergoing IVF does a mild ovarian stimulation strategy lead to comparable ongoing pregnancy rates in comparison to a conventional ovarian stimulation strategy? A mild ovarian stimulation strategy in women with poor ovarian reserve undergoing IVF leads to similar ongoing pregnancy rates as a conventional ovarian stimulation strategy. Women diagnosed with poor ovarian reserve are treated with a conventional ovarian stimulation strategy consisting of high-dose gonadotropins and pituitary downregulation with a long mid-luteal start GnRH-agonist protocol. Previous studies comparing a conventional strategy with a mild ovarian stimulation strategy consisting of low-dose gonadotropins and pituitary downregulation with a GnRH-antagonist have been under powered and their effectiveness is inconclusive. This open label multicenter randomized trial was designed to compare one cycle of a mild ovarian stimulation strategy consisting of low-dose gonadotropins (150 IU FSH) and pituitary downregulation with a GnRH-antagonist to one cycle of a conventional ovarian stimulation strategy consisting of high-dose gonadotropins (450 IU HMG) and pituitary downregulation with a long mid-luteal GnRH-agonist in women of advanced maternal age and/or women with poor ovarian reserve undergoing IVF between May 2011 and April 2014. Couples seeking infertility treatment were eligible if they fulfilled the following inclusion criteria: female age ≥35 years, a raised basal FSH level >10 IU/ml irrespective of age, a low antral follicular count of ≤5 follicles or poor ovarian response or cycle cancellation during a previous IVF cycle irrespective of age. The primary outcome was ongoing pregnancy rate per woman randomized. Analyses were on an intention-to-treat basis. We randomly assigned 195 women to the mild ovarian stimulation strategy and 199 women to the conventional ovarian stimulation strategy. Ongoing pregnancy rate was 12.8% (25/195) for mild

  11. Immune cells in the normal ovary and spontaneous ovarian tumors in the laying hen (Gallus domesticus) model of human ovarian cancer.

    Science.gov (United States)

    Bradaric, Michael J; Penumatsa, Krishna; Barua, Animesh; Edassery, Seby L; Yu, Yi; Abramowicz, Jacques S; Bahr, Janice M; Luborsky, Judith L

    2013-01-01

    Spontaneous ovarian cancer in chickens resembles human tumors both histologically and biochemically. The goal was to determine if there are differences in lymphocyte content between normal ovaries and ovarian tumors in chickens as a basis for further studies to understand the role of immunity in human ovarian cancer progression. Hens were selected using grey scale and color Doppler ultrasound to determine if they had normal or tumor morphology. Cells were isolated from ovaries (n = 6 hens) and lymphocyte numbers were determined by flow cytometry using antibodies to avian CD4 and CD8 T and B (Bu1a) cells. Ovarian sections from another set of hens (n = 26) were assessed to verify tumor type and stage and to count CD4, CD8 and Bu1a immunostained cells by morphometric analysis. T and B cells were more numerous in ovarian tumors than in normal ovaries by flow cytometry and immunohistochemistry. There were less CD4+ cells than CD8+ and Bu1a+ cells in normal ovaries or ovarian tumors. CD8+ cells were the dominant T cell sub-type in both ovarian stroma and in ovarian follicles compared to CD4+ cells. Bu1a+ cells were consistently found in the stroma of normal ovaries and ovarian tumors but were not associated with follicles. The number of immune cells was highest in late stage serous tumors compared to endometrioid and mucinous tumors. The results suggest that similar to human ovarian cancer there are comparatively more immune cells in chicken ovarian tumors than in normal ovaries, and the highest immune cell content occurs in serous tumors. Thus, this study establishes a foundation for further study of tumor immune responses in a spontaneous model of ovarian cancer which will facilitate studies of the role of immunity in early ovarian cancer progression and use of the hen in pre-clinical vaccine trials.

  12. Progress in the development of tooling and dismantling methodologies for the Windscale advanced gas cooled reactor (WAGR)

    International Nuclear Information System (INIS)

    Cross, M.T.; Wareing, M.I.; Dixon, C.

    1998-01-01

    Decommissioning of the Windscale Advanced Gas-Cooled Reactor (WAGR) is a major UK reactor decommissioning project co-funded by the UK Government, the European Commission and Magnox Electric. WAGR was a CO 2 cooled, graphite moderated reactor which served as a test bed for the development of Advanced Gas-Cooled Reactor technology in the UK. It operated from 1963 until shutdown in 1981. AEA Technology plc are currently the Managing Agents on behalf of UKAEA for the WAGR decommissioning project and are responsible for the co-ordination of the project up to the point when the contents of the reactor core and associated radioactive materials are removed and either disposed of or packaged for disposal at some time in the future. Decommissioning has progressed to the point where the reactor has been dismantled down to the level of the hot gas collection manifold with the removal of the top biological shield, the refuelling standpipes and the top section of the reactor pressure vessel. The 4 heat exchangers have also been removed and committed to shallow land burial. This paper describes the work carried out by AEA Technology under separate contracts of UKAEA in developing some of the equipment and deployment methods for the next phase of active operations required in preparation for the dismantling of the core structure. Most recent work has concentrated on the development of specialist tooling for removal of items of operational waste stored within the reactor core, equipment for cutting and removal of the highly radioactive stainless steel 'loop' pressure tubes, diamond wire cutting equipment for sectioning large diameter pipework, and equipment for dismantling the reactor neutron shield. The paper emphasises the process of adaptation and extension of existing technologies for cost-effective application in the decommissioning environment, the need for adequate forward planning of decommissioning methodologies together with large-scale 'mock-up' testing of equipment to

  13. Advanced light water reactor plants System 80+trademark design certification program. Annual progress report, October 1, 1994 - September 30, 1995

    International Nuclear Information System (INIS)

    1998-01-01

    The purpose of this report is to provide the status of the progress that was made towards Design Certification of System 80+trademark during the US government's 1995 fiscal year. The System 80+ Advanced Light Water Reactor (ALWR) is a 3931 MW (1350 MWe) Pressurized Water Reactor (PWR). The design covers an essentially complete plant. It is based on EPRI ALWR Utility Requirements Document (URD) improvements to the Standardized System 80 Nuclear Steam Supply System (NSSS) in operation at Palo Verde Units 1, 2, and 3. The NSSS is a traditional two-loop arrangement with two steam generators, two hot legs and four cold legs, each with a reactor coolant pump. The System 80+ standard design houses the NSSS in a spherical steel containment vessel which is enclosed in a concrete shield building, thus providing the safety advantages of a dual barrier to radioactivity release. Other major features include an all-digital, human-factors-engineered control room, an alternate electrical AC power source, an In-Containment Refueling Water Storage Tank (IRWST), and plant arrangements providing complete separation of redundant trains in safety systems

  14. Advanced light water reactor plants System 80+{trademark} design certification program. Annual progress report, October 1, 1994--September 30, 1995

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-09-01

    The purpose of this report is to provide the status of the progress that was made towards Design Certification of System 80+{trademark} during the US government`s 1995 fiscal year. The System 80+ Advanced Light Water Reactor (ALWR) is a 3931 MW (1350 MWe) Pressurized Water Reactor (PWR). The design covers an essentially complete plant. It is based on EPRI ALWR Utility Requirements Document (URD) improvements to the Standardized System 80 Nuclear Steam Supply System (NSSS) in operation at Palo Verde Units 1, 2, and 3. The NSSS is a traditional two-loop arrangement with two steam generators, two hot legs and four cold legs, each with a reactor coolant pump. The System 80+ standard design houses the NSSS in a spherical steel containment vessel which is enclosed in a concrete shield building, thus providing the safety advantages of a dual barrier to radioactivity release. Other major features include an all-digital, human-factors-engineered control room, an alternate electrical AC power source, an In-Containment Refueling Water Storage Tank (IRWST), and plant arrangements providing complete separation of redundant trains in safety systems.

  15. Distinct neural substrates of visuospatial and verbal-analytic reasoning as assessed by Raven's Advanced Progressive Matrices.

    Science.gov (United States)

    Chen, Zhencai; De Beuckelaer, Alain; Wang, Xu; Liu, Jia

    2017-11-24

    Recent studies revealed spontaneous neural activity to be associated with fluid intelligence (gF) which is commonly assessed by Raven's Advanced Progressive Matrices, and embeds two types of reasoning: visuospatial and verbal-analytic reasoning. With resting-state fMRI data, using global brain connectivity (GBC) analysis which averages functional connectivity of a voxel in relation to all other voxels in the brain, distinct neural correlates of these two reasoning types were found. For visuospatial reasoning, negative correlations were observed in both the primary visual cortex (PVC) and the precuneus, and positive correlations were observed in the temporal lobe. For verbal-analytic reasoning, negative correlations were observed in the right inferior frontal gyrus (rIFG), dorsal anterior cingulate cortex and temporoparietal junction, and positive correlations were observed in the angular gyrus. Furthermore, an interaction between GBC value and type of reasoning was found in the PVC, rIFG and the temporal lobe. These findings suggest that visuospatial reasoning benefits more from elaborate perception to stimulus features, whereas verbal-analytic reasoning benefits more from feature integration and hypothesis testing. In sum, the present study offers, for different types of reasoning in gF, first empirical evidence of separate neural substrates in the resting brain.

  16. Incremental Innovation and Progress in Advanced Squamous Cell Lung Cancer: Current Status and Future Impact of Treatment.

    Science.gov (United States)

    Langer, Corey J; Obasaju, Coleman; Bunn, Paul; Bonomi, Philip; Gandara, David; Hirsch, Fred R; Kim, Edward S; Natale, Ronald B; Novello, Silvia; Paz-Ares, Luis; Pérol, Maurice; Reck, Martin; Ramalingam, Suresh S; Reynolds, Craig H; Socinski, Mark A; Spigel, David R; Wakelee, Heather; Mayo, Carlos; Thatcher, Nick

    2016-12-01

    Squamous cell lung cancer (sqCLC) is an aggressive form of cancer that poses many therapeutic challenges. Patients tend to be older, present at a later stage, and have a high incidence of comorbidities, which can compromise treatment delivery and exacerbate toxicity. In addition, certain agents routinely available for nonsquamous cell histologic subtypes, such as bevacizumab and pemetrexed, are contraindicated or lack efficacy in sqCLC. Therapeutic progress has been much slower for advanced sqCLC, with median survival times of approximately 9 to 11 months in most studies. Herein, we discuss the current therapeutic landscape for patients with sqCLC versus with nonsquamous NSCLC. Current evidence indicates that new targeted treatments, notably monoclonal antibodies such as ramucirumab and necitumumab, and immunotherapies such as nivolumab and pembrolizumab can provide survival prolongation, although the benefits are still relatively modest. These incremental improvements, all realized since 2012, in aggregate, will very likely have a clinically meaningful impact for patients with sqCLC. We also discuss recent genomic studies of sqCLC that have identified potentially actionable molecular targets, as well as the relevant targeted agents in clinical development. Finally, we discuss the magnitude of survival benefit and the risk-to-benefit ratio that would prove clinically meaningful in this underserved patient population with unmet needs. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

  17. Advanced light water reactor plants System 80+trademark design certification program. Annual progress report, October 1, 1995 - September 30, 1996

    International Nuclear Information System (INIS)

    1996-01-01

    The purpose of this report is to provide a status of the progress that was made towards Design Certification of System 80+trademark during the US government's 1996 fiscal year. The System 80+ Advanced Light Water Reactor (ALWR) is a 3931 MW (1350 MWe) Pressurized Water Reactor (PWR). The design covers an essentially complete plant. It is based on EPRI ALWR Utility Requirements Document (URD) improvements to the Standardized System 80 Nuclear Steam Supply System (NSSS) in operation at Palo Verde Units 1, 2 and 3. The NSSS is a traditional two-loop arrangement with two steam generators, two hot legs and four cold legs, each with a reactor coolant pump. The System 80+ standard design houses the NSSS in a spherical steel containment vessel which is enclosed in a concrete shield building, thus providing the safety advantages of a dual barrier to radioactivity release. Other major features include an all-digital, human-factors-engineered control room, an alternate electrical AC power source, an In-Containment Refueling Water Storage Tank (IRWST), and plant arrangements providing complete separation of redundant trains in safety systems

  18. Female genital tract tuberculosis presenting as ovarian cancer

    Directory of Open Access Journals (Sweden)

    Malihe Hasanzadeh

    2014-01-01

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

  19. Ovarian volume throughout life

    DEFF Research Database (Denmark)

    Kelsey, Thomas W; Dodwell, Sarah K; Wilkinson, A Graham

    2013-01-01

    conception to 82 years of age. This model shows that 69% of the variation in ovarian volume is due to age alone. We have shown that in the average case ovarian volume rises from 0.7 mL (95% CI 0.4-1.1 mL) at 2 years of age to a peak of 7.7 mL (95% CI 6.5-9.2 mL) at 20 years of age with a subsequent decline...... to about 2.8 mL (95% CI 2.7-2.9 mL) at the menopause and smaller volumes thereafter. Our model allows us to generate normal values and ranges for ovarian volume throughout life. This is the first validated normative model of ovarian volume from conception to old age; it will be of use in the diagnosis......The measurement of ovarian volume has been shown to be a useful indirect indicator of the ovarian reserve in women of reproductive age, in the diagnosis and management of a number of disorders of puberty and adult reproductive function, and is under investigation as a screening tool for ovarian...

  20. The Quest for Item Types Based on Information Processing: An Analysis of Raven's Advanced Progressive Matrices, with a Consideration of Gender Differences

    Science.gov (United States)

    Vigneau, Francois; Bors, Douglas A.

    2008-01-01

    Various taxonomies of Raven's Advanced Progressive Matrices (APM) items have been proposed in the literature to account for performance on the test. In the present article, three such taxonomies based on information processing, namely Carpenter, Just and Shell's [Carpenter, P.A., Just, M.A., & Shell, P., (1990). What one intelligence test…

  1. National Research Council Dialogue to Assess Progress on NASA's Advanced Modeling, Simulation and Analysis Capability and Systems Engineering Capability Roadmap Development

    Science.gov (United States)

    Aikins, Jan

    2005-01-01

    Contents include the following: General Background and Introduction of Capability Roadmaps. Agency Objective. Strategic Planning Transformation. Advanced Planning Organizational Roles. Public Involvement in Strategic Planning. Strategic Roadmaps and Schedule. Capability Roadmaps and Schedule. Purpose of NRC Review. Capability Roadmap Development (Progress to Date).

  2. Premature ovarian failure and ovarian autoimmunity

    NARCIS (Netherlands)

    J.A. Schoemaker (Joop); H.A. Drexhage (Hemmo); A. Hoek (Annemieke)

    1997-01-01

    textabstractPremature ovarian failure (POF) is defined as a syndrome characterized by menopause before the age of 40 yr. The patients suffer from anovulation and hypoestrogenism. Approximately 1% of women will experience menopause before the age of 40 yr. POF is a

  3. Function of ovarian tissue after long-term storage.

    Science.gov (United States)

    Lieberman, Brian

    2012-08-01

    Ovarian tissue cryopreservation is one of the options available to preserve fertility in cancer patients and to allow them to conceive when they have overcome their primary disease. The publication of a report by Anderson and colleagues documenting live births in three women arising from ovarian cortical strips that had been transplanted more than 7 years previously represents an apparent further advance in this field. Copyright © 2012 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  4. Helplessness/hopelessness, minimization and optimism predict survival in women with invasive ovarian cancer: a role for targeted support during initial treatment decision-making?

    Science.gov (United States)

    Price, Melanie A; Butow, Phyllis N; Bell, Melanie L; deFazio, Anna; Friedlander, Michael; Fardell, Joanna E; Protani, Melinda M; Webb, Penelope M

    2016-06-01

    Women with advanced ovarian cancer generally have a poor prognosis but there is significant variability in survival despite similar disease characteristics and treatment regimens. The aim of this study was to determine whether psychosocial factors predict survival in women with ovarian cancer, controlling for potential confounders. The sample comprised 798 women with invasive ovarian cancer recruited into the Australian Ovarian Cancer Study and a subsequent quality of life study. Validated measures of depression, optimism, minimization, helplessness/hopelessness, and social support were completed 3-6 monthly for up to 2 years. Four hundred nineteen women (52.5 %) died over the follow-up period. Associations between time-varying psychosocial variables and survival were tested using adjusted Cox proportional hazard models. There was a significant interaction of psychosocial variables measured prior to first progression and overall survival, with higher optimism (adjusted hazard ratio per 1 standard deviation (HR) = 0.80, 95 % confidence interval (CI) 0.65-0.97), higher minimization (HR = 0.79, CI 0.66-0.94), and lower helplessness/hopelessness (HR = 1.40, CI 1.15-1.71) associated with longer survival. After disease progression, these variables were not associated with survival (optimism HR = 1.10, CI 0.95-1.27; minimization HR = 1.12, CI 0.95-1.31; and helplessness/hopelessness HR = 0.86, CI 0.74-1.00). Depression and social support were not associated with survival. In women with invasive ovarian cancer, psychosocial variables prior to disease progression appear to impact on overall survival, suggesting a preventive rather than modifying role. Addressing psychosocial responses to cancer and their potential impact on treatment decision-making early in the disease trajectory may benefit survival and quality of life.

  5. Ovarian Cancer and Comorbidity

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  6. Ovarian Cancer FAQ

    Science.gov (United States)

    ... vein thrombosis (DVT) , heart attack, and stroke. Current theories suggest that some types of ovarian cancer may ... Annual Meeting CME Overview CREOG Meetings Calendar Congressional Leadership Conference Advocacy Legislative Priorities GR & Outreach State Advocacy ...

  7. Management of ovarian cysts

    DEFF Research Database (Denmark)

    Knudsen, Ulla Breth; Tabor, Ann; Mosgaard, Berit Jul

    2004-01-01

    BACKGROUND: The treatment of an ovarian cyst relies on its nature, and accurate preoperative discrimination of benign and malignant cysts is therefore of crucial importance. This study was undertaken to review the literature concerning the preoperative diagnosis and treatment of ovarian cysts....... METHODS: Articles concerning ovarian cysts from a medline literature search during the period 1985-2003 were included in addition to articles found as references in the initial publications. RESULTS: Different methods for discriminating between benign and malignant ovarian cysts are discussed....... The diagnosis and the treatment are assessed in relation to age, menopausal status, pregnancy, and whether the cyst is presumed to be benign or malignant. In general, expectant management is the choice in premenopausal and pregnant women with non-suspicious cysts and normal levels of CA-125. In postmenopausal...

  8. Primary ovarian malignant melanoma

    Directory of Open Access Journals (Sweden)

    Kostov Miloš

    2010-01-01

    Full Text Available Background. Primary ovarian malignant melanoma is extremely rare. It usually appears in the wall of a dermoid cyst or is associated with another teratomatous component. Metastatic primary malignant melanoma to ovary from a primary melanoma elsewhere is well known and has been often reported especially in autopsy studies. Case report. We presented a case of primary ovarian malignant melanoma in a 45- year old woman, with no evidence of extraovarian primary melanoma nor teratomatous component. The tumor was unilateral, macroscopically on section presented as solid mass, dark brown to black color. Microscopically, tumor cells showed positive immunohistochemical reaction for HMB-45, melan-A and S-100 protein, and negative immunoreactivity for estrogen and progesteron receptors. Conclusion. Differentiate metastatic melanoma from rare primary ovarian malignant melanoma, in some of cases may be a histopathological diagnostic problem. Histopathological diagnosis of primary ovarian malignant melanoma should be confirmed by immunohistochemical analyses and detailed clinical search for an occult primary tumor.

  9. Clinicopathological and biological significance of aberrant activation of glycogen synthase kinase-3 in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Fu Y

    2014-06-01

    Full Text Available Yunfeng Fu,1 Xinyu Wang,1 Xiaodong Cheng,1 Feng Ye,2 Xing Xie,1,2 Weiguo Lu1,2 1Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, 2Women's Reproduction and Health Laboratory of Zhejiang Province, Hangzhou, People's Republic of China Background: Glycogen synthase kinase-3 (GSK-3 plays an important role in human cancer. The aim of this study is to evaluate the clinicopathological significance of expression of GSK-3α/β and pGSK-3α/βTyr279/216 in patients with epithelial ovarian cancer and to investigate whether GSK-3 inhibition can influence cell viability and tumor growth of ovarian cancer. Methods: Immunohistochemistry was used to examine expression of GSK-3α/β and pGSK-3α/βTyr279/216 in 71 human epithelial ovarian cancer tissues and correlations between protein expression, and clinicopathological factors were analyzed. Cell viability was determined by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay following exposure of ovarian carcinoma cells to pharmacological inhibitors of GSK-3 or GSK-3 small interfering RNA. In vivo validation of tumor growth inhibition was performed with xenograft mice. Results: The expression levels of GSK-3α/β and pGSK-3α/βTyr279/216 in ovarian cancers were significantly higher than those in benign tumors. High expression of GSK-3α/β was more likely to be found in patients with advanced International Federation of Gynecology and Obstetrics (FIGO stages and high serum cancer antigen 125. Higher expression of pGSK-3α/βTyr279/216 was associated with advanced FIGO stages, residual tumor mass, high serum cancer antigen 125, and poor chemoresponse. Worse overall survival was revealed by Kaplan–Meier survival curves in patients with high expression of GSK-3α/β or pGSK-3α/βTyr279/216. Multivariate analysis indicated that FIGO stage, GSK-3α/β expression, and pGSK-3α/βTyr279/216 expression were independent prognostic factors for overall

  10. Efficacy of doxorubicin after progression on carboplatin and paclitaxel in advanced or recurrent endometrial cancer: a retrospective analysis of patients treated at the Brazilian National Cancer Institute (INCA).

    Science.gov (United States)

    Moreira, Emeline; Paulino, Eduardo; Ingles Garces, Álvaro Henrique; Fontes Dias, Mariane S; Saramago, Marcos; de Moraes Lino da Silva, Flora; Thuler, Luiz Claudio Santos; de Melo, Andréia Cristina

    2018-01-31

    The treatment of endometrial cancer (EC) is challenging. There is no standard of care for patients who progressed after carboplatin and paclitaxel (CT) and all available drugs show a small response and poor long-term survival in this scenario. The objective of this study was to evaluate the efficacy and toxicity profile of palliative doxorubicin after progression to CT therapy in advanced or recurrent EC. A retrospective review of the Brazilian National Cancer Institute database between 2009 and 2013 was performed, and all patients with recurrent and advanced EC treated with palliative doxorubicin after progression on CT were included. Progression-free survival (PFS), overall survival (OS), objective response rates as well as toxicity were evaluated. A total of 33 patients were enrolled, with a median age of 65.7 years. Objective responses were documented in 12.1% (3.0% of complete responses and 9.1% of partial responses). The median PFS was 4.4 months, and the median OS was 8.1 months for patients exposed to doxorubicin. The most common adverse event was anemia observed in 60.6% of patients. This retrospective study suggests that doxorubicin has a modest activity in patients with advanced or recurrent EC after treatment with CT.

  11. Maternal undernutrition significantly impacts ovarian follicle number and increases ovarian oxidative stress in adult rat offspring.

    Directory of Open Access Journals (Sweden)

    Angelica B Bernal

    Full Text Available BACKGROUND: We have shown recently that maternal undernutrition (UN advanced female pubertal onset in a manner that is dependent upon the timing of UN. The long-term consequence of this accelerated puberty on ovarian function is unknown. Recent findings suggest that oxidative stress may be one mechanism whereby early life events impact on later physiological functioning. Therefore, using an established rodent model of maternal UN at critical windows of development, we examined maternal UN-induced changes in offspring ovarian function and determined whether these changes were underpinned by ovarian oxidative stress. METHODOLOGY/PRINCIPAL FINDINGS: Our study is the first to show that maternal UN significantly reduced primordial and secondary follicle number in offspring in a manner that was dependent upon the timing of maternal UN. Specifically, a reduction in these early stage follicles was observed in offspring born to mothers undernourished throughout both pregnancy and lactation. Additionally, antral follicle number was reduced in offspring born to all mothers that were UN regardless of whether the period of UN was restricted to pregnancy or lactation or both. These reductions were associated with decreased mRNA levels of genes critical for follicle maturation and ovulation. Increased ovarian protein carbonyls were observed in offspring born to mothers UN during pregnancy and/or lactation and this was associated with peroxiredoxin 3 hyperoxidation and reduced mRNA levels; suggesting compromised antioxidant defence. This was not observed in offspring of mothers UN during lactation alone. CONCLUSIONS: We propose that maternal UN, particularly at a time-point that includes pregnancy, results in reduced offspring ovarian follicle numbers and mRNA levels of regulatory genes and may be mediated by increased ovarian oxidative stress coupled with a decreased ability to repair the resultant oxidative damage. Together these data are suggestive of

  12. PEGylated liposome IHL-305 markedly improved the survival of ovarian cancer peritoneal metastasis in mouse

    International Nuclear Information System (INIS)

    Konishi, Hiroaki; Takagi, Akimitsu; Kurita, Akinobu; Kaneda, Norimasa; Matsuzaki, Takeshi

    2012-01-01

    Advanced ovarian cancer is characterized by peritoneal metastasis and the accumulation of ascites. Peritoneal metastasis of ovarian cancer is a major cause of the negative treatment outcome, as these metastases are resistant to most chemotherapy regimens. The aim of this study was to clarify aggressive pathology of peritoneal metastasis and examine the therapeutic efficacy of a liposomal agent in the model. A human cancer cell line ES-2 of ovarian clear cell carcinoma, known as a chemotherapy-resistant cancer, was cultured in nonadherent plate to form spheroid and single cell suspension was transplanted into mouse peritoneal cavity. The epidermal growth factor receptor (EGFR) pathways in the cellular aggregates were analyzed both spheroid and ascites. The pharmacokinetics and therapeutic efficacy of CPT-11 (45 mg/kg) and IHL-305 (45 mg/kg), an irinotecan-encapsulated liposome, were examined by intravenous administration. Established peritoneal metastasis model showed an accumulation of ascites. The activation of EGFR and Akt was demonstrated in cellular aggregates both in the spheroid and ascites. In ascites samples, the area under the curve of SN-38, the activated form of CPT-11, was 3.8 times higher from IHL-305-treated mice than from CPT-11-treated mice. IHL-305 prolonged the survival time and decreased the accumulation of ascites and tumor metastasis. The median survival time were 22, 37 and 54 days in the control, CPT-11-treated, and IHL-305-treated mice, respectively. EGFR/Akt pathway contributes to the aggressive progression in ES-2 peritoneal metastasis model and effective delivery into ascites of IHL-305 was thought to useful treatment for ovarian cancer with peritoneal metastasis

  13. Polycystic ovarian disease: animal models.

    Science.gov (United States)

    Mahajan, D K

    1988-12-01

    histologically, although some of the stromal cells appear hypertrophic. The anatomic features consequent to polycystic ovaries resulting from LL are similar to those in human PCOD, and both rat and human PCOD ovarian cells still retain the ability to respond to FSH/LH, LHRH, and unilateral ovariectomy. In the estradiol valerate rat model, although the anatomy and physiology of the ovary resemble those of PCOD patients, the progressive degeneration of the hypothalamus and the altered response of the pituitary to LHRH make this model inappropriate for studying the hypothalamic-pituitary-ovarian axis in the polycystic ovary condition.(ABSTRACT TRUNCATED AT 400 WORDS)

  14. Conservative management of epithelial ovarian cancer.

    Science.gov (United States)

    Dexeus, S; Labastida, R; Dexeus, D

    2005-01-01

    We are currently faced with a progressive delay in the age at which women conceive for the first time. This raises the possibility of the appearance of gynecologic disorders that may affect fertility, including neoplasms of the ovary. Fertility-sparing surgery is defined as the preservation of ovarian tissue in one or both adnexa and/or the uterus. Borderline ovarian tumor should be treated with conservative surgery. Salpingo-oophorectomy, or even ovarian cystectomy, are the procedures of choice, with recurrence rates of 2-3% and up to 20% if a simple cystectomy is performed. Cystectomy is indicated in patients with bilateral borderline tumors or in patients with a residual ovary. Borderline tumors with invasive peritoneal implants behave as an invasive cancer in 10-30% of cases with a survival rate of 10-66% compared with 100% in borderline tumors without invasive implants. Prophylactic oophorectomy is recommended when desire of conception has been accomplished. Conservative surgery in invasive epithelial ovarian cancer is limited to Stage IA, grade 1 tumor, and in some highly selected grade 2 tumors of serous, mucinous or endometrioid type, well-encapsulated and free of adhesions. The standard oncological surgical procedure with preservation of the uterus and normal appearing ovary is recommended. This includes salpingo-oophorectomy, excision of any suspicious peritoneal lesion, multiple peritoneal biopsies, appendectomy (particularly in mucinous tumors), and pelvic and paraaortic lymphadenectomy.

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

    International Nuclear Information System (INIS)

    Pignata, Sandro; Ghezzi, Fabio; Manzione, Luigi; Lauria, Rossella; Breda, Enrico; Alletti, Desiderio Gueli; Ballardini, Michela; Lombardi, Alessandra Vernaglia; Sorio, Roberto; Mangili, Giorgia; Priolo, Domenico; Ferrandina, Gabriella; Magni, Giovanna; Morabito, Alessandro; Scarfone, Giovanna; Scollo, Paolo; Odicino, Franco; Cormio, Gennaro; Katsaros, Dionyssios; Villa, Antonella; Mereu, Liliana

    2008-01-01

    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. 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. 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). This analysis shows that platinum sensitive mucinous ovarian cancer has a poor response to chemotherapy. Studies dedicated to this histological subgroup are needed

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

    Energy Technology Data Exchange (ETDEWEB)

    Pignata, Sandro [Istituto Nazionale Tumori, Napoli (Italy); Ghezzi, Fabio [Università dell' Insubria Clinica Ginecologia e Ostetrica, Varese (Italy); Manzione, Luigi [Azienda Ospedaliera S. Carlo, Oncologia Medica, Potenza (Italy); Lauria, Rossella [Università Federico II, Oncologia Medica, Napoli (Italy); Breda, Enrico [Ospedale S. Giovanni-Fatebene Fratelli-Isola Tiberina, Oncologia Medica, Roma (Italy); Alletti, Desiderio Gueli [A.O. Vincenzo Cervello, Ostetricia e Ginecologia, Palermo (Italy); Ballardini, Michela [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori - IRST, Meldola (FC) (Italy); Lombardi, Alessandra Vernaglia [Casa di cura Malzoni, Ginecologia Oncologica, Avellino (Italy); Sorio, Roberto [CRO AVIANO, Oncologia Medica, Aviano (Italy); Mangili, Giorgia [Ospedale S. Raffaele, Ginecologia Oncologica Medica, Milano (Italy); Priolo, Domenico [Ospedale S. Vincenzo, Oncologia Medica, Taormina (Italy); Ferrandina, Gabriella [Policlinico Agostino Gemelli, Ginecologia Oncologica, Roma (Italy); Magni, Giovanna [QBGROUP spa, Padova (Italy); Morabito, Alessandro [Istituto Nazionale Tumori, Napoli (Italy); Scarfone, Giovanna [Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Clinica Ostetrico-Ginecologica, Milano (Italy); Scollo, Paolo [A.O. S. Cannizzaro, Ginecologia ed Ostetricia, Catania (Italy); Odicino, Franco [A.O. Spedali Civili-Università degli Studi di Brescia, II Ginecologia ed Ostetricia, Brescia (Italy); Cormio, Gennaro [Azienda Ospedaliera Policlinico, II Ginecologia e Ostetricia, Bari (Italy); Katsaros, Dionyssios [Azienda Ospedaliera O.I.R.M.-S. Anna, Ginecologica Oncologica, Università di Torino (Italy); Villa, Antonella [Ospedali Riuniti di Bergamo, U.O. di Ginecologia, Bergamo (Italy); Mereu, Liliana [Ospedale Policlinico S. Matteo, Ostetrica e Ginecologica, Pavia (Italy)

    2008-09-01

    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. 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. 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). This analysis shows that platinum sensitive mucinous ovarian cancer has a poor response to chemotherapy. Studies dedicated to this histological subgroup are needed.

  17. 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.

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

    Science.gov (United States)

    Pignata, Sandro; Ferrandina, Gabriella; Scarfone, Giovanna; Scollo, Paolo; Odicino, Franco; Cormio, Gennaro; Katsaros, Dionyssios; Villa, Antonella; Mereu, Liliana; Ghezzi, Fabio; Manzione, Luigi; Lauria, Rossella; Breda, Enrico; Alletti, Desiderio Gueli; Ballardini, Michela; Lombardi, Alessandra Vernaglia; Sorio, Roberto; Mangili, Giorgia; Priolo, Domenico; Magni, Giovanna; Morabito, Alessandro

    2008-01-01

    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. PMID:18761742

  19. Normal-sized ovarian papillary serous carcinoma: a case report.

    Science.gov (United States)

    Wu, W C; Lai, C I; Huang, L C; Chiu, T H; Hung, Y C; Chang, W C

    2010-01-01

    A normal-sized ovarian papillary serous carcinoma is rare. We present the case of a 46-year-old woman with progressive abdominal fullness of one week's duration. The medical evaluation revealed abdominal carcinomatosis with normal-sized ovaries and an elevated serum CA-125 level of 147,365.8 U/ml. Cytoreductive surgery (hysterectomy, bilateral salpingo-oophorectomy, omentectomy, lymphadenectomy, infracolic omentectomy, peritoneal biopsy, washing cytology, and appendectomy) was performed. The histologic examination revealed an ovarian serous papillary carcinoma. Adjuvant chemotherapy was administered. The serum CA-125 level decreased after completion of treatment. Normal-sized ovarian serous surface papillary carcinomas should be kept in mind as an origin of disease in patients who have peritoneal carcinomatosis, which sometimes is a diagnostic dilemma of the disease source. We report this case to emphasize the clinical symptoms and importance of the early and accurate diagnosis of a normal-sized ovarian papillary serous carcinoma.

  20. Premature ovarian failure and ovarian autoimmunity

    OpenAIRE

    Schoemaker, Joop; Drexhage, Hemmo; Hoek, Annemieke

    1997-01-01

    textabstractPremature ovarian failure (POF) is defined as a syndrome characterized by menopause before the age of 40 yr. The patients suffer from anovulation and hypoestrogenism. Approximately 1% of women will experience menopause before the age of 40 yr. POF is a heterogeneous disorder with a multicausal pathogenesis involving chromosomal, genetic, enzymatic, infectious, and iatrogenic causes. There remains, however, a group of POF patients without a known etiology, the so-called "idiopathic...

  1. Multiple metastases from ovarian cancer

    African Journals Online (AJOL)

    Ovarian cancer affects women in the age group >60 years much ... ovarian cancer presenting with liver and thoracic vertebral metastases 4 months after ... manifested by parenchymal liver or lung ... categorised as stage Ic as per International.

  2. The Roles of Laparoscopy in Treating Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Chyi-Long Lee

    2009-03-01

    Full Text Available Great advances in technology offer meticulous options of minimally invasive surgery to empower the gynecologists to manage patients of early ovarian cancer. Laparoscopy affords improved visualization of the pelvic peritoneum, diaphragm and the deep pelvic structures, and offers many advantages in the avoidance of long abdominal incision, including shorter hospital stay and a more rapid recovery time. Most studies showed that laparoscopy did not compromise the survival and recurrence prognosis in comparison with open abdominal approach of staging surgery. Contrarily, laparoscopy precludes the advantage of open surgery, such as manual examination of the full extent of the bowel and palpation of lymph nodes. Besides, laparoscopy technically hampers the removal of large ovarian mass, and laparoscopic cancer surgery has a potential risk of trocar site metastasis. As the trend shows that laparoscopy has been playing an important role in treating early ovarian cancer, we could expect laparoscopy to become an attractive surgical option in the future for ovarian cancers.

  3. Natural history of autoimmune primary ovarian insufficiency in patients with Addison's disease: from normal ovarian function to overt ovarian dysfunction.

    Science.gov (United States)

    De Bellis, Annamaria; Bellastella, Giuseppe; Falorni, Alberto; Aitella, Ernesto; Barrasso, Mariluce; Maiorino, Maria Ida; Bizzarro, Elio; Bellastella, Antonio; Giugliano, Dario; Esposito, Katherine

    2017-10-01

    Women with autoimmune Addison's disease with normal ovulatory cycles but positive for steroid cell antibodies (StCA) have been considered at risk of premature ovarian insufficiency (POI). Thirty-three women younger than 40 years, with subclinical-clinical autoimmune Addison's disease but with normally ovulatory menses, were followed up for 10 years to evaluate the long-term time-related variations of StCA, ovarian function and follicular reserve. All patients and 27 control women were investigated at the start and every year for the presence and titre of StCA (by indirect immunofluorescence), serum concentrations of anti-Mullerian hormone (AMH) and ovarian function at four consecutive menses every year. At the start of the study StCA were present in 16 women (group 1), at low/middle titres (≤1:32) in seven of them (43.8%, group 1A), at high titres (>1:32) in the remaining nine patients (group 1B, 56.2%), while they were absent from 17 patients (group 2). During the follow-up period, all women in group 1A remained StCA-positive at low/middle titres with normal ovulatory menses and normal gonadotrophin and AMH levels, while all patients in group 1B showed a further increase of StCA titres (1:128-1:256) and progressed through three stages of ovarian function. None of the patients in group 2 and controls showed the appearance of StCA or ovarian dysfunction during the follow-up. The presence of StCA at high titres can be considered a good predictive marker of subsequent development of autoimmune POI. To single out the stages of autoimmune POI may allow a timely therapeutic choice in the subclinical and early clinical stages. © 2017 European Society of Endocrinology.

  4. SPONTANEOUS RESOLUTION OF ANTENATALY DIAGNOSED COMPLEX OVARIAN CYST - A FOLLOW UP SONOGRAPHIC STUDY

    OpenAIRE

    Satyabhuwan Singh; Vishnu; Vivek; Rajesh; Sanjay

    2014-01-01

    A congenital ovarian cyst in feto - neonatal stage is a rare condition. New advanced Ultrasonography technique increased the incidences. Though benign, large cyst and complex cysts may require surgical management. We fol lowed one case of complex feto - neonatal ovarian cyst till complete resolution.

  5. The role of the addition of ovarian suppression to tamoxifen in young women with hormone-sensitive breast cancer who remain premenopausal or regain menstruation after chemotherapy (ASTRRA): study protocol for a randomized controlled trial and progress

    International Nuclear Information System (INIS)

    Kim, Hyun-Ah; Ahn, Sei Hyun; Nam, Seok Jin; Park, Seho; Ro, Jungsil

    2016-01-01

    Ovarian function suppression (OFS) has been shown to be effective as adjuvant endocrine therapy in premenopausal women with hormone receptor-positive breast cancer. However, it is currently unclear if addition of OFS to standard tamoxifen therapy after completion of adjuvant chemotherapy results in a survival benefit. In 2008, the Korean Breast Cancer Society Study Group initiated the ASTRRA randomized phase III trial to evaluate the efficacy of OFS in addition to standard tamoxifen treatment in hormone receptor-positive breast cancer patients who remain or regain premenopausal status after chemotherapy. Premenopausal women with estrogen receptor-positive breast cancer treated with definitive surgery were enrolled after completion of neoadjuvant or adjuvant chemotherapy. Ovarian function was assessed at the time of enrollment and every 6 months for 2 years by follicular-stimulating hormone levels and bleeding history. If ovarian function was confirmed as premenopausal status, the patient was randomized to receive 2 years of goserelin plus 5 years of tamoxifen treatment or 5 years of tamoxifen alone. The primary end point will be the comparison of the 5-year disease-free survival rates between the OFS and tamoxifen alone groups. Patient recruitment was finished on March 2014 with the inclusion of a total of 1483 patients. The interim analysis will be performed at the time of the observation of the 187th event. This study will provide evidence of the benefit of OFS plus tamoxifen compared with tamoxifen only in premenopausal patients with estrogen receptor-positive breast cancer treated with chemotherapy

  6. PTH levels and not serum phosphorus levels are a predictor of the progression of kidney disease in elderly patients with advanced chronic kidney disease.

    Science.gov (United States)

    Toapanta Gaibor, Néstor Gabriel; Nava Pérez, Nathasha Carolina; Martínez Echevers, Yeleine; Montes Delgado, Rafael; Guerrero Riscos, María Ángeles

    At present, there is a high incidence of elderly patients with advanced chronic kidney disease (CKD) and it is important to know the long term progression and the factors that influence it. To analyse the progression of advanced CKD in elderly patients and the influence of bone-mineral metabolism. Retrospective study of 125 patients ≥70years of age with CKD stages 4-5 who started follow-up from January 1, 2007 to December 31, 2008, showing the progression of CKD (measured by the slope of the regression line of the estimated glomerular filtration rate [eGFR] by MDRD-4) over 5years. Progression in the entire group (median and 25th and 75th percentiles): -1.15 (-2.8/0.17) ml/min/1.73m 2 /year, CKD-4: -1.3 (-2.8/0.03) ml/min/1.73m 2 /year, CKD-5: -1.03 (-3.0/0.8) ml/min/1.73m 2 /year; the slope of the regression line was positive in 35 patients (28%: CKD does not progress) and negative in 90 patients (72%: CKD progresses). Negative correlation (Spearman) (slower progression): PTH, albumin/Cr ratio and daily Na excretion (all baseline measurements). No correlation with eGFR, serum P, urinary P excretion, protein intake and intake of P (all baseline measurements). In the linear regression analysis (dependent variable: slope of progression): albuminuria and PTH (both at baseline measurements) influenced this variable independently. Logistic regression (progresses vs. does not progress): PTH, albuminuria and eGFR (all at baseline measurements) influenced significantly. In our group of elderly patients, impairment of renal function is slow, particularly in CKD-5 patients. Albuminuria and PTH at baseline levels are prognostic factors in the evolution of renal function. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  7. Appendectomy in the surgical staging of ovarian carcinoma.

    Science.gov (United States)

    Beşe, T; Kösebay, D; Kaleli, S; Oz, A U; Demirkiran, F; Gezer, A

    1996-06-01

    Extensive debulking is accepted as the primary method of operative management for carcinoma of the ovary. However, there is no consensus regarding the role of appendectomy in primary surgical treatment. The aim of this study was to assess the role of appendectomy in the surgical staging and cytoreduction of ovarian carcinoma. The study was a retrospective review of 90 primary malignant ovarian carcinoma patients who had an appendectomy in addition to primary cytoreductive surgery. Out of 90 patients, 10 (11.1%) had metastasis to the appendix. The rate of metastasis to the appendix was 11.5% (9/78) in malignant epithelial ovarian carcinomas and 8.3% (1/12) in non-epithelial ovarian tumors. Of the patients with metastasis in the appendix, malignant epithelial ovarian tumors were identified in 90% (serous: 70%; clear cell: 20%), and non-epithelial malignant ovarian tumor were disclosed in 10% (granulosa cell carcinoma). There were no metastases to the appendix in the other histological types. Although metastasis to the appendix was not observed in early stage ovarian carcinomas, it was detected in 21.4% (9/42) of stage III and 50% (1/2) of stage IV. Macroscopic tumor metastasis in the abdomen was noted in all patients with metastasis to the appendix. Appendectomy for stage I and II patients was not beneficial and did not affect final staging. As a result, for the proper staging of ovarian carcinoma there is no advantage to the addition of routine appendectomy to primary cytoreductive surgery in early stage (stage I and II) malignant epithelial ovarian tumors. Appendectomy would contribute to the cytoreduction of advanced stage disease if it is macroscopically involved.

  8. Functional expression of TWEAK and the receptor Fn14 in human malignant ovarian tumors: possible implication for ovarian tumor intervention.

    Directory of Open Access Journals (Sweden)

    Liying Gu

    Full Text Available The aim of this current study was to investigate the expression of the tumor necrosis factor (TNF-like weak inducer of apoptosis (TWEAK and its receptor fibroblast growth factor-inducible 14 (Fn14 in human malignant ovarian tumors, and test TWEAK's potential role on tumor progression in cell models in-vitro. Using immunohistochemistry (IHC, we found that TWEAK and its receptor Fn14 were expressed in human malignant ovarian tumors, but not in normal ovarian tissues or in borderline/benign epithelial ovarian tumors. High levels of TWEAK expression was detected in the majority of malignant tumors (36 out of 41, 87.80%. Similarly, 35 out of 41 (85.37% malignant ovarian tumors were Fn14 positive. In these malignant ovarian tumors, however, TWEAK/Fn14 expression was not corrected with patients' clinical subtype/stages or pathological features. In vitro, we demonstrated that TWEAK only inhibited ovarian cancer HO-8910PM cell proliferation in combination with tumor necrosis factor-α (TNF-α, whereas either TWEAK or TNF-α alone didn't affect HO-8910PM cell growth. TWEAK promoted TNF-α production in cultured THP-1 macrophages. Meanwhile, conditioned media from TWEAK-activated macrophages inhibited cultured HO-8910PM cell proliferation and invasion. Further, TWEAK increased monocyte chemoattractant protein-1 (MCP-1 production in cultured HO-8910PM cells to possibly recruit macrophages. Our results suggest that TWEAK/Fn14, by activating macrophages, could be ovarian tumor suppressors. The unique expression of TWEAK/Fn14 in malignant tumors indicates that it might be detected as a malignant ovarian tumor marker.

  9. Treatment of ovarian cancer ascites by intra-peritoneal injection of diphtheria toxin A chain-H19 vector: a case report

    Directory of Open Access Journals (Sweden)

    Abu-lail Rasha

    2010-07-01

    Full Text Available Abstract Introduction Ovarian cancer ascitic fluid, which contains malignant cells, is usually present in women with an advanced stage disease. There are currently no effective therapies for the treatment of ovarian cancer ascitic fluid. We developed a new therapeutic strategy to target expression of the diphtheria toxin fragment A gene in ovarian tumor cells under the control of H19 regulatory sequences. Case presentation A 64-year-old Caucasian woman was diagnosed with a stage IIIc epithelial ovarian cancer. She suffered from progressive disease, accumulation of malignant ascites that needed to be drained weekly, abdominal pain, vomiting, anorexia and severe weakness. Infusion of the diphtheria toxin A chain-H19 plasmid into the peritoneum of our patient resulted in complete resolution of the ascites with minimum adverse events. Conclusion On the basis of this preliminary experience, we are currently conducting an extensive Phase I study on a larger number of patients in order to assess the safety and preliminary efficacy of this novel patient-oriented treatment approach.

  10. Trastuzumab beyond progression in human epidermal growth factor receptor 2-positive advanced breast cancer: a german breast group 26/breast international group 03-05 study

    DEFF Research Database (Denmark)

    von Minckwitz, Gunter; du Bois, Andreas; Schmidt, Marcus

    2009-01-01

    PURPOSE: Trastuzumab shows clinical activity in human epidermal growth factor receptor 2 (HER-2)-positive early and advanced breast cancer. In the German Breast Group 26/Breast International Group 03-05 trial, we investigated if trastuzumab treatment should be continued beyond progression. METHODS......: Patients with HER-2-positive breast cancer that progresses during treatment with trastuzumab were randomly assigned to receive capecitabine (2,500 mg/m(2) body-surface area on days 1 through 14 [1,250 mg/m(2) semi-daily]) alone or with continuation of trastuzumab (6 mg/kg body weight) in 3-week cycles....... The primary end point was time to progression. RESULTS: We randomly assigned 78 patients to capecitabine and 78 patients to capecitabine plus trastuzumab. Sixty-five events and 38 deaths in the capecitabine group and 62 events and 33 deaths in the capecitabine-plus-trastuzumab group occurred during 15...

  11. Plasminogen activator inhibitor-1 is an independent prognostic factor of ovarian cancer and IMD-4482, a novel plasminogen activator inhibitor-1 inhibitor, inhibits ovarian cancer peritoneal dissemination.

    Science.gov (United States)

    Nakatsuka, Erika; Sawada, Kenjiro; Nakamura, Koji; Yoshimura, Akihito; Kinose, Yasuto; Kodama, Michiko; Hashimoto, Kae; Mabuchi, Seiji; Makino, Hiroshi; Morii, Eiichi; Yamaguchi, Yoichi; Yanase, Takeshi; Itai, Akiko; Morishige, Ken-Ichirou; Kimura, Tadashi

    2017-10-27

    In the present study, the therapeutic potential of targeting plasminogen activator inhibitor-1 (PAI-1) in ovarian cancer was tested. Tissues samples from 154 cases of ovarian carcinoma were immunostained with anti-PAI-1 antibody, and the prognostic value was analyzed. Among the samples, 67% (104/154) showed strong PAI-1 expression; this was significantly associated with poor prognosis (progression-free survival: 20 vs. 31 months, P = 0.0033). In particular, among patients with stage II-IV serous adenocarcinoma, PAI-1 expression was an independent prognostic factor. The effect of a novel PAI-1 inhibitor, IMD-4482, on ovarian cancer cell lines was assessed and its therapeutic potential was examined using a xenograft mouse model of ovarian cancer. IMD-4482 inhibited in vitro cell adhesion to vitronectin in PAI-1-positive ovarian cancer cells, followed by the inhibition of extracellular signal-regulated kinase and focal adhesion kinase phosphorylation through dissociation of the PAI-urokinase receptor complex from integrin αVβ3. IMD-4482 caused G0/G1 cell arrest and inhibited the proliferation of PAI-1-positive ovarian cancer cells. In the xenograft model, IMD-4482 significantly inhibited peritoneal dissemination with the reduction of PAI-1 expression and the inhibition of focal adhesion kinase phosphorylation. Collectively, the functional inhibition of PAI-1 significantly inhibited ovarian cancer progression, and targeting PAI-1 may be a potential therapeutic strategy in ovarian cancer.

  12. A genetically engineered ovarian cancer mouse model based on fallopian tube transformation mimics human high-grade serous carcinoma development.

    Science.gov (United States)

    Sherman-Baust, Cheryl A; Kuhn, Elisabetta; Valle, Blanca L; Shih, Ie-Ming; Kurman, Robert J; Wang, Tian-Li; Amano, Tomokazu; Ko, Minoru S H; Miyoshi, Ichiro; Araki, Yoshihiko; Lehrmann, Elin; Zhang, Yongqing; Becker, Kevin G; Morin, Patrice J

    2014-07-01

    Recent evidence suggests that ovarian high-grade serous carcinoma (HGSC) originates from the epithelium of the fallopian tube. However, most mouse models are based on the previous prevailing view that ovarian cancer develops from the transformation of the ovarian surface epithelium. Here, we report the extensive histological and molecular characterization of the mogp-TAg transgenic mouse, which expresses the SV40 large T-antigen (TAg) under the control of the mouse müllerian-specific Ovgp-1 promoter. Histological analysis of the fallopian tubes of mogp-TAg mice identified a variety of neoplastic lesions analogous to those described as precursors to ovarian HGSC. We identified areas of normal-appearing p53-positive epithelium that are similar to 'p53 signatures' in the human fallopian tube. More advanced proliferative lesions with nuclear atypia and epithelial stratification were also identified that were morphologically and immunohistochemically reminiscent of human serous tubal intraepithelial carcinoma (STIC), a potential precursor of ovarian HGSC. Beside these non-invasive precursor lesions, we also identified invasive adenocarcinoma in the ovaries of 56% of the mice. Microarray analysis revealed several genes differentially expressed between the fallopian tube of mogp-TAg and wild-type (WT) C57BL/6. One of these genes, Top2a, which encodes topoisomerase IIα, was shown by immunohistochemistry to be concurrently expressed with elevated p53 and was specifically elevated in mouse STICs but not in the surrounding tissues. TOP2A protein was also found elevated in human STICs, low-grade and high-grade serous carcinoma. The mouse model reported here displays a progression from normal tubal epithelium to invasive HGSC in the ovary, and therefore closely simulates the current emerging model of human ovarian HGSC pathogenesis. This mouse therefore has the potential to be a very useful new model for elucidating the mechanisms of serous ovarian tumourigenesis, as well as

  13. Atezolizumab in platinum-treated locally advanced or metastatic urothelial carcinoma: post-progression outcomes from the phase II IMvigor210 study.

    Science.gov (United States)

    Necchi, A; Joseph, R W; Loriot, Y; Hoffman-Censits, J; Perez-Gracia, J L; Petrylak, D P; Derleth, C L; Tayama, D; Zhu, Q; Ding, B; Kaiser, C; Rosenberg, J E

    2017-12-01

    Conventional criteria for tumor progression may not fully reflect the clinical benefit of immunotherapy or appropriately guide treatment decisions. The phase II IMvigor210 study demonstrated the efficacy and safety of atezolizumab, a programmed death-ligand 1-directed antibody, in patients with platinum-treated locally advanced or metastatic urothelial carcinoma. Patients could continue atezolizumab beyond Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 progression at the investigator's discretion: this analysis assessed post-progression outcomes in these patients. Patients were treated with atezolizumab 1200 mg i.v. every 3 weeks until loss of clinical benefit. Efficacy and safety outcomes in patients who experienced RECIST v1.1 progression and did, or did not, continue atezolizumab were analyzed descriptively. In total, 220 patients who experienced progression from the overall cohort (n = 310) were analyzed: 137 continued atezolizumab for ≥ 1 dose after progression, 19 received other systemic therapy, and 64 received no further systemic therapy. Compared with those who discontinued, patients continuing atezolizumab beyond progression were more likely to have had a baseline Eastern Cooperative Oncology Group performance status of 0 (43.1% versus 31.3%), less likely to have had baseline liver metastases (27.0% versus 41.0%), and more likely to have had an initial response to atezolizumab (responses in 11.7% versus 1.2%). Five patients (3.6%) continuing atezolizumab after progression had subsequent responses compared with baseline measurements. Median post-progression overall survival was 8.6 months in patients continuing atezolizumab, 6.8 months in those receiving another treatment, and 1.2 months in those receiving no further treatment. Atezolizumab exposure-adjusted adverse event frequencies were generally similar before and following progression. In this single-arm study, patients who continued atezolizumab beyond RECIST v1

  14. Ovarian Stem Cell Nests in Reproduction and Ovarian Aging.

    Science.gov (United States)

    Ye, Haifeng; Zheng, Tuochen; Li, Wei; Li, Xiaoyan; Fu, Xinxin; Huang, Yaoqi; Hu, Chuan; Li, Jia; Huang, Jian; Liu, Zhengyv; Zheng, Liping; Zheng, Yuehui

    2017-01-01

    The fixed primordial follicles pool theory, which monopolized reproductive medicine for more than one hundred years, has been broken by the discovery, successful isolation and establishment of ovarian stem cells. It has brought more hope than ever of increasing the size of primordial follicle pool, improving ovarian function and delaying ovarian consenescence. Traditional view holds that stem cell aging contributes to the senility of body and organs. However, in the process of ovarian aging, the main factor leading to the decline of the reproductive function is the aging and degradation of ovarian stem cell nests, rather than the senescence of ovarian germ cells themselves. Recent studies have found that the immune system and circulatory system are involved in the formation of ovarian germline stem cell niches, as well as regulating the proliferation and differentiation of ovarian germline stem cells through cellular and hormonal signals. Therefore, we can improve ovarian function and delay ovarian aging by improving the immune system and circulatory system, which will provide an updated program for the treatment of premature ovarian failure (POF) and infertility. © 2017 The Author(s). Published by S. Karger AG, Basel.

  15. Ovarian tubercular abscess mimicking ovarian carcinoma: A rare case report

    Directory of Open Access Journals (Sweden)

    Abinash Agarwala

    2015-01-01

    Full Text Available Although genito-urinary tuberculosis is common, reports of isolated ovarian tubercular abscess are rare. Ovarian tubercular abscess may mimics that of an ovarian tumor, leading to diagnostic difficulties. We reported a case report of 35 years woman presented with chronic pain abdomen, weight loss, low-grade fever and a right ovarian mass on ultrasound, with a significantly elevated CA-125 level. On clinical and radiological evidence, diagnosis of ovarian carcinoma was made, and laparotomy was performed with resection of the ovary. Postoperative specimen sent for histological examination that revealed classic epithelioid granuloma and acid-fast bacilli were present in Ziehl-Neelsen stain. Patient was put on antitubercular regimen from our Dots center. She is improving clinical after taking antitubercular drug and is on regular follow up at our chest outpatient department. Ovarian tubercular abscess is common in young women living in endemic zones, but case report of isolated tubercular abscess is rarely reported. CA-125 can be raised in both ovarian tubercular abscess and ovarian carcinoma, and only imaging is not always conclusive. Laparotomy followed by tissue diagnosis can be helpful in this situation. As the prognosis and treatment outcome of ovarian tubercular abscess and ovarian carcinoma is different, proper diagnosis by laparotomy should be done. Early diagnosis of ovarian tubercular abscess is vital as untreated disease can lead to infertility.

  16. Treatment Choice for Advanced Non-small Cell Lung Cancer Patients Who Had Gradual Progression After EGFR-TKIs: 32 Cases Report

    Directory of Open Access Journals (Sweden)

    Lin LIN

    2013-10-01

    Full Text Available Background and objective The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs have been widely used in the treatment of the advanced non-small cell lung cancer (NSCLC, especially in the adenocarcinoma patients with activating EGFR mutations. But there is no published overview of the following treatment. This report through observing the efficacy, toxicity and overall survival of different treatments to the advanced NSCLC patients who had gradual progression after EGFR-TKIs, evaluates the influence of the continued treatment and switching chemotherapy. Methods Retrospective review is conducted on 32 cases of advanced NSCLC patients who experienced treatment failure of EGFR-TKIs. One group accepted the continued treatment and the other group accepted the switching chemotherapy. Results The median overall survival of the continued treatment group is 36.0 months. The respose rate of the switching chemotherapy group is 43.75%, and clinical benefit rate (complete and partial response and stable disease is 87.5%. The median overall survival is 15.5 months. The main toxicities are nausea, vomiting and hematological toxicities. Conclusion For the advanced NSCLC patients who had gradual progression after EGFR-TKIs, the continued treatment is one of the acceptable choices.

  17. Mathematical Models of Breast and Ovarian Cancers

    Science.gov (United States)

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

    2016-01-01

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

  18. Ovarian cancer surgery

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  19. Papillary ovarian cystadenocarcinoma in a dog.

    Science.gov (United States)

    Yotov, S; Simeonov, R; Dimitrov, F; Vassilev, N; Dimitrov, M; Georgiev, P

    2005-03-01

    An 11-year-old female German Shepherd dog was presented for investigation of progressive enlargement of the abdomen, periodic bloody discharge from the vulva and rapid exhaustion. Transabdominal ultrasonography and lateral abdominal radiography demonstrated an echogenic formation with anechogenic cavities located cranial to the urinary bladder and a homogeneous shadow with an elliptical shape was located caudal to the rib arc. Both showed indistinct borders. Exploratory laparotomy identified bilateral ovarian masses and ovariohysterectomy was performed. Histopathology confirmed ovarian cystadenocarcinoma. The dog remained clinically normal without evidence of metastatic disease 4 months after surgery. Papillary cystadenocarcinoma in the bitch could affect both ovaries and manifests with a rapid growth rate and clinical signs such as rapid exhaustion, abdominal enlargement and vulval discharge. Ovariohysterectomy is the treatment option.

  20. Use of common analgesic medications and ovarian cancer survival

    DEFF Research Database (Denmark)

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

    2017-01-01

    BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with improved survival in some cancers, but evidence for ovarian cancer is limited. METHODS: Pooling individual-level data from 12 Ovarian Cancer Association Consortium studies, we evaluated the association between self......-reported, pre-diagnosis use of common analgesics and overall/progression-free/disease-specific survival among 7694 women with invasive epithelial ovarian cancer (4273 deaths). RESULTS: Regular analgesic use (at least once per week) was not associated with overall survival (pooled hazard ratios, pHRs (95......% confidence intervals): aspirin 0.96 (0.88-1.04); non-aspirin NSAIDs 0.97 (0.89-1.05); acetaminophen 1.01 (0.93-1.10)), nor with progression-free/disease-specific survival. There was however a survival advantage for users of any NSAIDs in studies clearly defining non-use as less than once per week (pHR=0...

  1. Assessing risk of fibrosis progression and liver-related clinical outcomes among patients with both early stage and advanced chronic hepatitis C.

    Directory of Open Access Journals (Sweden)

    Monica A Konerman

    Full Text Available Assessing risk of adverse outcomes among patients with chronic liver disease has been challenging due to non-linear disease progression. We previously developed accurate prediction models for fibrosis progression and clinical outcomes among patients with advanced chronic hepatitis C (CHC. The primary aim of this study was to validate fibrosis progression and clinical outcomes models among a heterogeneous patient cohort.Adults with CHC with ≥3 years follow-up and without hepatic decompensation, hepatocellular carcinoma (HCC, liver transplant (LT, HBV or HIV co-infection at presentation were analyzed (N = 1007. Outcomes included: 1 fibrosis progression 2 hepatic decompensation 3 HCC and 4 LT-free survival. Predictors included longitudinal clinical and laboratory data. Machine learning methods were used to predict outcomes in 1 and 3 years.The external cohort had a median age of 49.4 years (IQR 44.3-54.3; 61% were male, 80% white, and 79% had genotype 1. At presentation, 73% were treatment naïve and 31% had cirrhosis. Fibrosis progression occurred in 34% over a median of 4.9 years (IQR 3.2-7.6. Clinical outcomes occurred in 22% over a median of 4.4 years (IQR 3.2-7.6. Model performance for fibrosis progression was limited due to small sample size. The area under the receiver operating characteristic curve (AUROC for 1 and 3-year risk of clinical outcomes was 0.78 (95% CI 0.73-0.83 and 0.76 (95% CI 0.69-0.81.Accurate assessments for risk of clinical outcomes can be obtained using routinely collected data across a heterogeneous cohort of patients with CHC. These methods can be applied to predict risk of progression in other chronic liver diseases.

  2. 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.

  3. Advanced Technology Section semiannual progress report, April 1-September 30, 1977. Volume 1. Biotechnology and environmental programs. [Lead Abstract

    Energy Technology Data Exchange (ETDEWEB)

    Pitt, W.W. Jr.; Mrochek, J.E. (comps.)

    1980-06-01

    Research efforts in six areas are reported. They include: centrifugal analyzer development; advanced analytical systems; environmental research; bioengineering research;bioprocess development and demonstration; and, environmental control technology. Individual abstracts were prepared for each section for ERA/EDB. (JCB)

  4. Update of progress for Phase II of B&W`s advanced coal-fired low-emission boiler system

    Energy Technology Data Exchange (ETDEWEB)

    McDonald, D.K. [Babcock & Wilcox, Barberton, OH (United States); Madden, D.A.; Rodgers, L.W. [Babcock & Wilcox, Alliance, OH (United States)] [and others

    1995-11-01

    Over the past five years, advances in emission control techniques at reduced costs and auxiliary power requirements coupled with significant improvements in steam turbine and cycle design have significantly altered the governing criteria by which advanced technologies have been compared. With these advances, it is clear that pulverized coal technology will continue to be competitive in both cost and performance with other advanced technologies such as Integrated Gasification Combined Cycle (IGCC) or first generation Pressurized Fluidized Bed Combustion (PFBC) technologies for at least the next decade. In the early 1990`s it appeared that if IGCC and PFBC could achieve costs comparable to conventional pulverized coal plants, their significantly reduced NO{sub x} and SO{sub 2} emissions would make them more attractive. A comparison of current emission control capabilities shows that all three technologies can already achieve similarly low emissions levels.

  5. Current concepts on burn wound conversion – a review of recent advances in understanding the secondary progressions of burns

    Science.gov (United States)

    Salibian, Ara A.; Del Rosario, Angelica Tan; De Almeida Moura Severo, Lucio; Nguyen, Long; Banyard, Derek A.; Toranto, Jason D.; Evans, Gregory R.D.; Widgerow, Alan D.

    2016-01-01

    Burn wound conversion describes the process by which superficial partial thickness burns convert into deeper burns necessitating surgical intervention. Fully understanding and thus controlling this phenomenon continues to defy burn surgeons. However, potentially guiding burn wound progression so as to obviate the need for surgery while still bringing about healing with limited scarring is the major unmet challenge. Comprehending the pathophysiologic background contributing to deeper progression of these burns is an essential prerequisite to planning any intervention. In this study, a review of articles examining burn wound progression over the last five years was conducted to analyze trends in recent burn progression research, determine changes in understanding of the pathogenesis of burn conversion, and subsequently examine the direction for future research in developing therapies. The majority of recent research focuses on applying therapies from other disease processes to common underlying pathogenic mechanisms in burn conversion. While ischemia, inflammation, and free oxygen radicals continue to demonstrate a critical role in secondary necrosis, novel mechanisms such as autophagy have also been shown to contribute affect significantly burn progression significantly. Further research will have to determine whether multiple mechanisms should be targeted when developing clinical therapies. PMID:26787127

  6. Premature ovarian failure

    OpenAIRE

    Pacheco, José

    2011-01-01

    Premature ovarian failure is characterized by secondary amenorrhea affecting a woman before the age of 40, leading to hypoestrogenism, infertility, and consequences of premature menopause, such as osteoporosis, cardiovascular disease, neurovegetative alterations, and others. Follicular exhaustion is due to either follicles shortage or oocytes accelerated destruction. Main causes are genetic, autoimmune and iatrogenic. Among genetic causes Xq and Xp deletions, translocations, numeric aberratio...

  7. Polycystic ovarian syndrome

    OpenAIRE

    Nina Madnani; Kaleem Khan; Phulrenu Chauhan; Girish Parmar

    2013-01-01

    Polycystic ovarian syndrome (PCOS) is a "multispeciality" disorder suspected in patients with irregular menses and clinical signs of hyperandrogenism such as acne, seborrhoea, hirsutism, irregular menses, infertility, and alopecia. Recently, PCOS has been associated with the metabolic syndrome. Patients may develop obesity, insulin resistance, acanthosis nigricans, Type 2 diabetes, dyslipidemias, hypertension, non-alcoholic liver disease, and obstructive sleep apnoea. Good clinical examinatio...

  8. Association of Ovarian Tumor β2-Adrenergic Receptor Status with Ovarian Cancer Risk Factors and Survival.

    Science.gov (United States)

    Huang, Tianyi; Tworoger, Shelley S; Hecht, Jonathan L; Rice, Megan S; Sood, Anil K; Kubzansky, Laura D; Poole, Elizabeth M

    2016-12-01

    The β 2 -adrenergic signaling pathway mediates the effects of chronic stress on ovarian cancer progression in mouse models. The relevance of this pathway to human ovarian cancer remains unknown. We assessed tumor expression of β 2 -adrenergic receptor (ADRB2) using tissue microarrays in 237 ovarian cancer cases from the Nurses' Health Studies (NHS/NHSII). Competing risks Cox regression was used to evaluate whether associations of reproductive, hormonal, and psychosocial factors with ovarian cancer risk differed by ADRB2. We also examined the association between tumor ADRB2 expression and ovarian cancer survival. Forty-five (19%) cases were positive for ADRB2 staining. High levels of anxiety symptoms were positively associated with ADRB2-positive tumors (HR, 2.59; 95% confidence interval [CI], 1.15-5.84) but not with ADRB2-negative tumors (HR, 1.16; 95% CI, 0.81-1.66; P heterogeneity = 0.07). We observed similar results for depression. No associations were observed for job strain, caregiving stress, or widowhood for either positive or negative ADRB2 status. Lifetime ovulatory years were more strongly associated with ADRB2-positive tumors (HR per 5 years, 1.60; 95% CI, 1.15-2.21) compared with ADRB2-negative tumors (HR, 1.11; 95% CI, 0.96-1.27; P heterogeneity = 0.04). Significant heterogeneity by ADRB2 was also observed for parity (P heterogeneity = 0.01), oral contraceptive use (P heterogeneity = 0.03), and age at menopause (P heterogeneity = 0.04). Tumor expression of ADRB2 was not associated with ovarian cancer mortality (HR, 1.05; 95% CI, 0.69-1.59). Several stress- and ovulation-related factors were differentially associated with ovarian tumors responsive to β 2 -adrenergic signaling. Replication in larger studies is warranted to confirm the role of β 2 -adrenergic signaling in ovarian cancer etiology. Cancer Epidemiol Biomarkers Prev; 25(12); 1587-94. ©2016 AACR. ©2016 American Association for Cancer Research.

  9. New advances of TMEM88 in cancer initiation and progression, with special emphasis on Wnt signaling pathway.

    Science.gov (United States)

    Ge, Yun-Xuan; Wang, Chang-Hui; Hu, Fu-Yong; Pan, Lin-Xin; Min, Jie; Niu, Kai-Yuan; Zhang, Lei; Li, Jun; Xu, Tao

    2018-01-01

    Transmembrane protein 88 (TMEM88), a newly discovered protein localized on the cell membrane. Recent studies showed that TMEM88 was involved in the regulation of several types of cancer. TMEM88 was expressed at significantly higher levels in breast cancer (BC) cell line than in normal breast cell line with co-localized with Dishevelled (DVL) in the cytoplasm of BC cell line. TMEM88 silencing in the ovarian cancer cell line CP70 resulted in significant upregulation of Wnt downstream genes (c-Myc, cyclin-D1) and other Wnt target genes including JUN, PTIX2, CTNNB1 (β-catenin), further supporting that TMEM88 inhibits canonical Wnt signaling pathway. Wnt signaling pathway has been known to play important roles in many diseases, especially in cancer. For instance, hepatocellular carcinoma (HCC) has become one of the most common tumors harboring mutations in the Wnt signaling pathway. As the inhibitor of Wnt signaling, TMEM88 has been considered to act as an oncogene or a tumor suppressor. Up-regulated TMEM88 or gene therapy approaches could be an effective therapeutic approach against tumor as TMEM88 inhibits Wnt signaling through direct interaction with DVL. Here, we review the current knowledge on the functional role and potential clinical application of TMEM88 in the control of various cancers. Highlights Wnt signaling displays an important role in several pathogenesis of cancer. Wnt signaling pathway is activated during cancer development. TMEM88 has an impact on cancer by inhibiting canonical Wnt signaling. We discuss the importance and new applications of TMEM88 in cancer therapy. © 2017 Wiley Periodicals, Inc.

  10. Iron addiction: a novel therapeutic target in ovarian cancer

    International Nuclear Information System (INIS)

    Basuli, D.

    2017-01-01

    Ovarian cancer is a lethal malignancy that has not seen a major therapeutic advance in over 30 years. We demonstrate that ovarian cancer exhibits a targetable alteration in iron metabolism. Ferroportin (FPN), the iron efflux pump, is decreased, and transferrin receptor (TFR1), the iron importer, is increased in tumor tissue from patients with high grade but not low grade serous ovarian cancer. A similar profile of decreased FPN and increased TFR1 is observed in a genetic model of ovarian cancer tumor-initiating cells (TICs). The net result of these changes is an accumulation of excess intracellular iron and an augmented dependence on iron for proliferation. A forced reduction in intracellular iron reduces the proliferation of ovarian cancer TICs in vitro, and inhibits both tumor growth and intraperitoneal dissemination of tumor cells in vivo. Some mechanistic studies demonstrate that iron increases metastatic spread by facilitating invasion through expression of matrix metalloproteases and synthesis of interleukin 6 (IL-6). Here, we show that the iron dependence of ovarian cancer TICs renders them exquisitely sensitive in vivo to agents that induce iron-dependent cell death (ferroptosis) as well as iron chelators, and thus creates a metabolic vulnerability that can be exploited therapeutically.

  11. The role of appendectomy in surgical procedures for ovarian cancer.

    Science.gov (United States)

    Fontanelli, R; Paladini, D; Raspagliesi, F; di Re, E

    1992-07-01

    To assess the role of appendectomy in the surgical procedures for ovarian cancer, we evaluated retrospectively the clinical charts of 435 patients who underwent surgery after diagnosis of ovarian cancer. The appendix was removed in 160 cases and pathological examination revealed 37 with metastatic implants (23%). All the patients with appendiceal metastases showed advanced disease (stages III-IV) with an incidence of 43%. Ninety-one percent (31/34) of the tumors with appendiceal involvement at the staging operation were of the serous cell type and grade II or III. No case with early stage, right ovary carcinoma showed appendiceal metastatic foci, denying the existence of a preferential lymphatic pathway. Microscopic involvement was found only in 4 patients with advanced disease (11.7%). No intra- or postoperative complication directly related to the appendectomy was recorded. We conclude, with these results, that appendectomy should be part of the cytoreductive operation for ovarian cancer.

  12. Personalized biomarkers to monitor disease progression in advanced non-small-cell lung cancer patients treated with icotinib.

    Science.gov (United States)

    Song, Gaoguang; Liu, Yujie; Wang, Yanying; Ren, Guanjun; Guo, Shuai; Ren, Junling; Zhang, Li; Li, Zhili

    2015-02-02

    Disease-specific humoral immune response-related protein complexes in blood are associated with disease progression. Thirty-one patients with stage IIIB and IV non-small-cell lung cancer (NSCLC) were administered with oral dose of icotinib hydrochloride (150 mg twice daily or 125 mg 3 times daily) for a 28-continuous-day cycle until diseases progressed or unacceptable toxicity occurred. The levels of immunoinflammation-related protein complexes (IIRPCs) in a series of plasma samples from 31 NSCLC patients treated with icotinib hydrochloride were determined by an optimized native polyacrylamide gel electrophoresis. Three characteristic patterns of the IIRPCs, named as patterns a, b, and c, respectively, were detected in plasma samples from 31 patients. Prior to the treatment, there were 18 patients in pattern a consisting of 5 IIRPCs, 9 in pattern b consisting of six IIRPCs, and 4 in pattern c without the IIRPCs. The levels of the IIRPCs in 27 patients were quantified. Our results indicate that the time length of humoral immune and inflammation response (TLHIIR) was closely associated with disease progression, and the median TLHIIR was 22.0 weeks, 95% confidence interval: 16.2 to 33.0 weeks, with a lead time of median 11 weeks relative to clinical imaging evidence confirmed by computed tomography or magnetic resonance imaging (the median progression-free survival, 34.0 weeks, 95% confidence interval: 27.9 to 49.0 weeks). The complex relationships between humoral immune response, acquired resistance, and disease progression existed. Personalized IIRPCs could be indicators to monitor the disease progression. Copyright © 2014 Elsevier B.V. All rights reserved.

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  14. The role of EMMPRIN expression in ovarian epithelial carcinomas.

    Science.gov (United States)

    Zhao, Yang; Chen, Shuo; Gou, Wen-feng; Niu, Zhe-feng; Zhao, Shuang; Xiao, Li-jun; Takano, Yasuo; Zheng, Hua-chuan

    2013-09-01

    Extracellular matrix metalloproteinase inducer (EMMPRIN) was reported to involve in the invasion and metastasis of malignancies by regulating the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) in stromal and cancer cells. The study aimed to clarify the role of EMMPRIN expression in tumorigenesis and progression of ovarian epithelial carcinomas. EMMPRIN siRNA were transfected into ovarian carcinoma cells with the phenotypes and their related molecules examined. EMMPRIN expression was determined in ovarian normal tissue, benign and borderline tumors, and epithelial carcinomas by real-time PCR, western blot, and immunohistochemistry. EMMPRIN siRNA treatment resulted in a lower growth, G 1 arrest, apoptotic induction, decreased migration, and invasion. The transfectants showed reduced expression of Wnt5a, Akt, p70s6k, Bcl-xL, survivin, VEGF, and MMP-9 than mock and control cells at both mRNA and protein levels. According to real-time PCR and western blot, EMMPRIN mRNA or protein level was higher in ovarian borderline tumor and carcinoma than normal ovary and benign tumors (PEMMPRIN expression was positively correlated with FIGO staging, dedifferentiation, Ki-67 expression, the lower cumulative and relapse-free survival rate (PEMMPRIN protein and mRNA might be involved in the pathogenesis, differentiation, and progression of ovarian carcinomas, possibly by modulating cellular events, such as proliferation, cell cycle, apoptosis, migration, and invasion.

  15. Effect of Yushen zhuyun decoction on rats with diminished ovarian ...

    African Journals Online (AJOL)

    biogenesis in cumulus cells. Hum Reprod 2015; 30: 1653-1664. 7. Feng JH, Kong LW, Li LL. Research progress of pathogeny and treatment of traditional Chinese and. Western medicine of decreasing ovarian reservation. Chin Med Hera 2014; 11: 161-164. 8. Roustan A, Perrin J, Debals-Gonthier M, Paulmyer-. Lacroix O ...

  16. Ovarian chocolate cysts

    International Nuclear Information System (INIS)

    Sugimura, Kazuro; Ishida, Tetsuya; Takemori, Masayuki; Kitagaki, Hajime; Tanaka, Yutaka; Yamasaki, Katsuhito; Shimizu, Tadafumi; Kono, Michio.

    1988-01-01

    Accurate preoperative staging of ovarian chocolate cysts is very important because recent hormonal therapy has been effective in low stage patients. However, it has been difficult to assess the preoperative stage of ovarian chocolate cysts. We evaluated the diagnostic potential of MRI in preoperative staging of 15 overian chocolate cysts. It was well known that the older the ovarian chocolate cyst was the more iron content it had. We examined the iron contents effect on T1 and T2 relaxation times in surgically confirmed chocolate cysts (stage II: 3 cases, stage III: 3 cases and stage IV: 9 cases by AFS classification, 1985) employing the 0.15-T MR system and 200 MHz spectrometer. There was a positive linear relation between T1 of the lesion using the MR system (T1) and T1 of the resected contents using the spectrometer (sp-T1); r = 0.93. The same relation was revealed between T2 and sp-T2; r = 0.87. It was indicated that T1 and T2 using the MR system was accurate. There was a negative linear relation between T1 and the iron contents ( r = -0.81) but no relation between T2 and the iron contents. T1 was 412 ± 91 msec for stage II, 356 ± 126 msec for stage III and 208 ± 30 msec for stage IV. T1 for stage IV was shorter than that for stage II and III, statistically significant differences were noted (p < 0.05). Thus, T1 was useful in differentiating a fresh from an old ovarian chocolate cyst. We concluded that T1 relaxation time using the MR system was useful for the staging of an ovarian chocolate cyst without surgery. (author)

  17. Dysregulated estrogen receptor signaling in the hypothalamic-pituitary-ovarian axis leads to ovarian epithelial tumorigenesis in mice.

    Directory of Open Access Journals (Sweden)

    Mary J Laws

    2014-03-01

    Full Text Available The etiology of ovarian epithelial cancer is poorly understood, mainly due to the lack of an appropriate experimental model for studying the onset and progression of this disease. We have created a mutant mouse model in which aberrant estrogen receptor alpha (ERα signaling in the hypothalamic-pituitary-ovarian axis leads to ovarian epithelial tumorigenesis. In these mice, termed ERαd/d, the ERα gene was conditionally deleted in the anterior pituitary, but remained intact in the hypothalamus and the ovary. The loss of negative-feedback regulation by estrogen (E at the level of the pituitary led to increased production of luteinizing hormone (LH by this tissue. Hyperstimulation of the ovarian cells by LH resulted in elevated steroidogenesis, producing high circulating levels of steroid hormones, including E. The ERαd/d mice exhibited formation of palpable ovarian epithelial tumors starting at 5 months of age with 100% penetrance. By 15 months of age, 80% of ERαd/d mice die. Besides proliferating epithelial cells, these tumors also contained an expanded population of luteinized stromal cells, which acquire the ability to express P450 aromatase and synthesize E locally. In response to the elevated levels of E, the ERα signaling was accentuated in the ovarian epithelial cells of ERαd/d mice, triggering increased ERα-dependent gene expression, abnormal cell proliferation, and tumorigenesis. Consistent with these findings, treatment of ERαd/d mice with letrozole, an aromatase inhibitor, markedly reduced circulating E and ovarian tumor volume. We have, therefore, developed a unique animal model, which serves as a useful tool for exploring the involvement of E-dependent signaling pathways in ovarian epithelial tumorigenesis.

  18. Targeting Stromal-Cancer Cell Crosstalk Networks in Ovarian Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Tsz-Lun Yeung

    2016-01-01

    Full Text Available Ovarian cancer is a histologically, clinically, and molecularly diverse disease with a five-year survival rate of less than 30%. It has been estimated that approximately 21,980 new cases of epithelial ovarian cancer will be diagnosed and 14,270 deaths will occur in the United States in 2015, making it the most lethal gynecologic malignancy. Ovarian tumor tissue is composed of cancer cells and a collection of different stromal cells. There is increasing evidence that demonstrates that stromal involvement is important in ovarian cancer pathogenesis. Therefore, stroma-specific signaling pathways, stroma-derived factors, and genetic changes in the tumor stroma present unique opportunities for improving the diagnosis and treatment of ovarian cancer. Cancer-associated fibroblasts (CAFs are one of the major components of the tumor stroma that have demonstrated supportive roles in tumor progression. In this review, we highlight various types of signaling crosstalk between ovarian cancer cells and stromal cells, particularly with CAFs. In addition to evaluating the importance of signaling crosstalk in ovarian cancer progression, we discuss approaches that can be used to target tumor-promoting signaling crosstalk and how these approaches can be translated into potential ovarian cancer treatment.

  19. Reduced ovarian glyoxalase-I activity by dietary glycotoxins and androgen excess: a causative link to polycystic ovarian syndrome.

    Science.gov (United States)

    Kandaraki, Eleni; Chatzigeorgiou, Antonis; Piperi, Christina; Palioura, Eleni; Palimeri, Sotiria; Korkolopoulou, Penelope; Koutsilieris, Michael; Papavassiliou, Athanasios G

    2012-10-24

    Glyoxalase detoxification system composed of glyoxalase (GLO)-I and GLO-II is ubiquitously expressed and implicated in the protection against cellular damage because of cytotoxic metabolites such as advanced glycation end products (AGEs). Recently, ovarian tissue has emerged as a new target of excessive AGE deposition and has been associated with either a high AGE diet in experimental animals or hyperandrogenic disorders such as polycystic ovarian syndrome (PCOS) in humans. This study was designed to investigate the impact of dietary AGEs and androgens in rat ovarian GLO-I activity of normal nonandrogenized (NAN, group A, n = 18) and androgenized prepubertal (AN) rats (group B, n = 29). Both groups were further randomly assigned, either to a high-AGE (HA) or low-AGE (LA) diet for 3 months. The activity of ovarian GLO-I was significantly reduced in normal NAN animals fed an HA diet compared with an LA diet (p = 0.006). Furthermore, GLO-I activity was markedly reduced in AN animals compared with NAN (p ≤ 0.001) when fed with the corresponding diet type. In addition, ovarian GLO-I activity was positively correlated with the body weight gain (r(s) = 0.533, p androgen levels. Modification of ovarian GLO-I activity, observed for the first time in this androgenized prepubertal rat model, may present a contributing factor to the reproductive dysfunction characterizing PCOS.

  20. Comparison of minichromosome maintenance proteins (MCM-3, MCM-7) and metallothioneins (MT-I/II, MT-III) expression in relation to clinicopathological data in ovarian cancer.

    Science.gov (United States)

    Kobierzycki, Christopher; Pula, Bartosz; Skiba, Mateusz; Jablonska, Karolina; Latkowski, Krzysztof; Zabel, Maciej; Nowak-Markwitz, Ewa; Spaczynski, Marek; Kedzia, Witold; Podhorska-Okolow, Marzena; Dziegiel, Piotr

    2013-12-01

    Despite great progress in the understanding of ovarian cancer biology, clinicopathological data (i.e. grade, stage, histological type and residual disease after surgery) seem to be the most important prognostic factors. The present study aimed to investigate the relationship between expression of minichromosome maintenance proteins (MCM-3, MCM-7), metallothioneins (MT-I/II, MT-III), and Ki-67 in 103 ovarian cancer cases, mostly of the serous histological type. Statistical analysis revealed strong positive correlations in the expression of MCM-3 vs. Ki-67 (r=0.492), MCM-7 vs. Ki-67 (r=0.651), and MCM-3 vs. MCM-7 (r=0.515) (all pMCM-3 and Ki-67 with increasing grade of histological malignancy (p=0.0011, p=0.029, respectively). Regarding clinical progression, cytoplasmic MT-I/II expression was significantly higher in more advanced disease stages (III+IV vs. I+II; p=0.0247). Due to the correlations shown here, the determination of MCM proteins as proliferation markers of ovarian cancer, should be strongly considered.

  1. Progress Monitoring Change in Children's Social, Emotional, and Behavioral Functioning: Advancing the State of the Science

    Science.gov (United States)

    Owens, Julie Sarno; Evans, Steven W.

    2018-01-01

    The studies in this special series examine the effectiveness of direct behavior ratings (DBRs) for use as a progress monitoring tool. In this article, we comment on the findings of the studies in the context of the broader school-based assessment movement and discuss areas for future inquiry within this line of research.

  2. The AP600 advanced simplified nuclear power plant. Results of the test program and progress made toward final design approval

    International Nuclear Information System (INIS)

    Bruschi, H.J.

    1996-01-01

    At the 1994 Pacific Basin Conference, Mr. Bruschi presented a paper describing the AP600, Westinghouse's advanced light water reactor design with passive safety features. Since then, a rigorous test program was completed and AP600 became the most thoroughly tested advanced reactor system design in history. Westinghouse is now well on its way toward receiving Final Design Approval from the U.S. Nuclear Regulatory Commission for AP600. In this paper, the results of the test program will be discussed and an update on prospects for building the plant will be covered. (author)

  3. The AP600 advanced simplified nuclear power plant. Results of the test program and progress made toward final design approval

    Energy Technology Data Exchange (ETDEWEB)

    Bruschi, H.J. [Westinghouse Electric Corp., Pittsburgh, PA (United States)

    1996-10-01

    At the 1994 Pacific Basin Conference, Mr. Bruschi presented a paper describing the AP600, Westinghouse`s advanced light water reactor design with passive safety features. Since then, a rigorous test program was completed and AP600 became the most thoroughly tested advanced reactor system design in history. Westinghouse is now well on its way toward receiving Final Design Approval from the U.S. Nuclear Regulatory Commission for AP600. In this paper, the results of the test program will be discussed and an update on prospects for building the plant will be covered. (author)

  4. 3'-Deoxy-3'-18F-fluorothymidine positron emission tomography as an early predictor of disease progression in patients with advanced and metastatic pancreatic cancer

    International Nuclear Information System (INIS)

    Challapalli, Amarnath; Barwick, Tara; Merchant, Shairoz; Pearson, Rachel A.; Howell, Elizabeth C.; Maxwell, Ross J.; Mauri, Francesco; Sumpter, Katherine; Aboagye, Eric O.; Sharma, Rohini

    2015-01-01

    3'-Deoxy-3'- 18 F-fluorothymidine (FLT) positron emission tomography (PET) has limited utility in abdominal imaging due to high physiological hepatic uptake of tracer. We evaluated FLT PET/CT combined with a temporal-intensity information-based voxel-clustering approach termed kinetic spatial filtering (FLT PET/CT KSF ) for early prediction of response and survival outcomes in locally advanced and metastatic pancreatic cancer patients receiving gemcitabine-based chemotherapy. Dynamic FLT PET/CT data were collected before and 3 weeks after the first cycle of chemotherapy. Changes in tumour FLT PET/CT variables were determined. The primary end point was RECIST 1.1 response on contrast-enhanced CT after 3 months of therapy. Twenty patients were included. Visual distinction between tumours and normal pancreas was seen in FLT PET KSF images. All target lesions (>2 cm), including all primary pancreatic tumours, were visualised. Of the 11 liver metastases, 3 (<2 cm) were not visible after kinetic filtering. Of the 20 patients, 7 progressed (35 %). Maximum standardised uptake value at 60 min post-injection (SUV 60,max ) significantly increased in patients with disease progression (p = 0.04). Receiver-operating characteristic curve analysis indicated that a threshold of SUV 60,max increase of ≥ 12 % resulted in sensitivity, specificity and positive predictive value (PPV) of 71, 100 and 100 %, respectively [area under the curve (AUC) 0.90, p = 0.0001], to predict patients with disease progression. Changes in SUV 60,max were not predictive of survival. FLT PET/CT detected changes in proliferation, with early increase in SUV 60,max predicting progressive disease with a high specificity and PPV. Therefore, FLT PET/CT could be used as an early response biomarker for gemcitabine-based chemotherapy, to select a poor prognostic group who may benefit from novel therapeutic agents in advanced and metastatic pancreatic cancer. (orig.)

  5. Three new genetic loci (R1210C in CFH, variants in COL8A1 and RAD51B) are independently related to progression to advanced macular degeneration.

    Science.gov (United States)

    Seddon, Johanna M; Reynolds, Robyn; Yu, Yi; Rosner, Bernard

    2014-01-01

    To assess the independent impact of new genetic variants on conversion to advanced stages of AMD, controlling for established risk factors, and to determine the contribution of genes in predictive models. In this prospective longitudinal study of 2765 individuals, 777 subjects progressed to neovascular disease (NV) or geographic atrophy (GA) in either eye over 12 years. Recently reported genetic loci were assessed for their independent effects on incident advanced AMD after controlling for 6 established loci in 5 genes, and demographic, behavioral, and macular characteristics. New variants which remained significantly related to progression were then added to a final multivariate model to assess their independent effects. The contribution of genes to risk models was assessed using reclassification tables by determining risk within cross-classified quintiles for alternative models. THREE NEW GENETIC VARIANTS WERE SIGNIFICANTLY RELATED TO PROGRESSION: rare variant R1210C in CFH (hazard ratio (HR) 2.5, 95% confidence interval [CI] 1.2-5.3, P = 0.01), and common variants in genes COL8A1 (HR 2.0, 95% CI 1.1-3.5, P = 0.02) and RAD51B (HR 0.8, 95% CI 0.60-0.97, P = 0.03). The area under the curve statistic (AUC) was significantly higher for the 9 gene model (.884) vs the 0 gene model (.873), P = .01. AUC's for the 9 vs 6 gene models were not significantly different, but reclassification analyses indicated significant added information for more genes, with adjusted odds ratios (OR) for progression within 5 years per one quintile increase in risk score of 2.7, Padvanced AMD beyond macular and behavioral phenotypes.

  6. The latest animal models of ovarian cancer for novel drug discovery.

    Science.gov (United States)

    Magnotti, Elizabeth; Marasco, Wayne A

    2018-03-01

    Epithelial ovarian cancer is a heterogeneous disease classified into five subtypes, each with a different molecular profile. Most cases of ovarian cancer are diagnosed after metastasis of the primary tumor and are resistant to traditional platinum-based chemotherapeutics. Mouse models of ovarian cancer have been utilized to discern ovarian cancer tumorigenesis and the tumor's response to therapeutics. Areas covered: The authors provide a review of mouse models currently employed to understand ovarian cancer. This article focuses on advances in the development of orthotopic and patient-derived tumor xenograft (PDX) mouse models of ovarian cancer and discusses current humanized mouse models of ovarian cancer. Expert opinion: The authors suggest that humanized mouse models of ovarian cancer will provide new insight into the role of the human immune system in combating and augmenting ovarian cancer and aid in the development of novel therapeutics. Development of humanized mouse models will take advantage of the NSG and NSG-SGM3 strains of mice as well as new strains that are actively being derived.

  7. Multiple Cutaneous Metastases as Initial Presentation in Advanced Colon Cancer

    Directory of Open Access Journals (Sweden)

    Sudheer Nambiar

    2018-01-01

    Full Text Available Skin metastases from advanced colorectal cancer are relatively rare and occur most often when the cancer is advanced, following the spread to other organs. Cutaneous metastases occur in about 3% of advanced colorectal cancers. We present an extremely rare case of a 68-year-old woman with advanced ascending colon adenocarcinoma that presented with multiple rapidly progressing painless cutaneous metastatic lesions with no other distant metastases. Of all the tumors, breast cancer most commonly spreads as cutaneous metastasis is followed by lung, colorectal, renal, ovarian, and bladder cancers. Cutaneous metastases can present in a variety of clinical manifestations, such as a rapidly growing painless dermal or subcutaneous nodule with intact overlying epidermis or as ulcers. In cases where the cutaneous deposit is isolated, as in visceral metastasis, there is a role for radical management such as wide local excision and reconstruction. In our patient, since she had multiple cutaneous metastases she began treatment with palliative systemic combination chemotherapy.

  8. Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037)

    DEFF Research Database (Denmark)

    Weber, Jeffrey S; D'Angelo, Sandra P; Minor, David

    2015-01-01

    BACKGROUND: Nivolumab, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, can result in durable responses in patients with melanoma who have progressed after ipilimumab and BRAF inhibitors. We assessed the efficacy and safety of nivolumab compared with investigator's choice......, and progressed after ipilimumab, or ipilimumab and a BRAF inhibitor if they were BRAF(V 600) mutation-positive. Participating investigators randomly assigned (with an interactive voice response system) patients 2:1 to receive an intravenous infusion of nivolumab 3 mg/kg every 2 weeks or ICC (dacarbazine 1000 mg......-protocol after 120 patients had been treated with nivolumab and had a minimum follow-up of 24 weeks, and safety in all patients who had had at least one dose of treatment. The trial is closed and this is the first interim analysis, reporting the objective response primary endpoint. This study is registered...

  9. Progress in high energy physics and nuclear safety : Proceedings of the NATO Advanced Research Workshop on Safe Nuclear Energy

    CERN Document Server

    Polański, Aleksander; Begun, Viktor

    2009-01-01

    The book contains recent results on the progress in high-energy physics, accelerator, detection and nuclear technologies, as well as nuclear safety in high-energy experimentation and in nuclear industry, covered by leading experts in the field. The forthcoming experiments at the Large Hadron Collider (LHC) at CERN and cosmic-ray experiments are highlighted. Most of the current high-energy experiments and their physical motivation are analyzed. Various nuclear energy safety aspects, including progress in the production of new radiation-resistant materials, new and safe nuclear reactor designs, such as the slowly-burning reactor, as well as the use of coal-nuclear symbiotic methods of energy production can be found in the book.

  10. Towards prevention of ovarian cancer.

    Science.gov (United States)

    Ali, Aus Tariq

    2018-01-01

    Ovarian cancer is the leading cause of death of all gynaecological cancers. To date, there is no reliable, specific screening procedure for detecting ovarian cancer. The risk factors of ovarian cancer include modifiable and non-modifiable factors. The main goal of the ovarian cancer prevention program is to significantly reduce the risk of development of ovarian cancer and other cancers such as breast and/or peritoneal cancer. The application of non-surgical preventive approaches such as oral contraceptives, parity and breastfeeding has been shown to be highly protective against ovarian cancer development. Targeting inflammation has been also reported to be associated with a protective trend against ovarian cancer and can be achieved through either non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin or lifestyle modifications or both. Lifestyle modification that includes regular exercise, healthy diet supplemented with anti-oxidants and anti-inflammatory elements reduces the risk of the disease even further. Surgical protective approaches include; tubal ligation, hysterectomy and prophylactic bilateral salpingo-oophorectomy and the former is the most effective approach to protect against ovarian cancer. A better understanding of the risk factors of ovarian cancer and the current approaches to prevent it may increase the awareness and help to decrease the incidence of ovarian cancer, increase the five-year survival rate and decrease the mortality rate significantly in the general population especially among those at high risk for ovarian cancer. This review is an attempt to outline a potential program of ovarian cancer prevention and the potential challenges. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. Leukocyte-associated immunoglobulin-like receptor-1 expressed in epithelial ovarian cancer cells and involved in cell proliferation and invasion

    International Nuclear Information System (INIS)

    Cao, Qizhi; Fu, Aili; Yang, Shude; He, Xiaoli; Wang, Yue; Zhang, Xiaoshu; Zhou, Jiadi; Luan, Xiying; Yu, Wenzheng; Xue, Jiangnan

    2015-01-01

    Previous studies have shown that leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is expressed on most types of hamatopoietic cells and negatively regulate immune response, but the roles of LAIR-1 in tumor of the non-hematopoietic lineage have not been determined. Despite advances in therapy of epithelial ovarian cancer (EOC), many questions relating to EOC pathogenesis remain unanswered. The aim of this study was to investigate the clinical significance of LAIR-1 expression in EOC and explore the possible association between LAIR-1 and cancer. In this study, a tissue microarray containing 78 ovarian cancer cases was stained following a standard immunohistochemical protocol for LAIR-1 and the correlation of LAIR-1 expression with clinicopathologic features was assessed. LAIR-1 was detected to express in tumor cells of ovarian cancer tissues (73.1%) and EOC cell lines COC1 and HO8910, not in normal ovarian tissues. In addition, LAIR-1 expression correlates significantly with tumor grade (p = 0.004). Furthermore, down-regulation of LAIR-1 in HO8910 cells increased cell proliferation, colony formation and cell invasion. These data suggest that LAIR-1 has a relevant impact on EOC progression and may be helpful for a better understanding of molecular pathogenesis of cancer. - Highlights: • LAIR-1 is expressed in epithelial ovarian cancer cells. • LAIR-1 expression correlates significantly with tumor grade. • Down-regulation of LAIR-1 expression increased cell proliferation and invasion. • LAIR-1 may be a novel candidate for cancer diagnosis and therapy

  12. Follicle-Stimulating Hormone Receptor Is Expressed by Most Ovarian Cancer Subtypes and Is a Safe and Effective Immunotherapeutic Target.

    Science.gov (United States)

    Perales-Puchalt, Alfredo; Svoronos, Nikolaos; Rutkowski, Melanie R; Allegrezza, Michael J; Tesone, Amelia J; Payne, Kyle K; Wickramasinghe, Jayamanna; Nguyen, Jenny M; O'Brien, Shane W; Gumireddy, Kiranmai; Huang, Qihong; Cadungog, Mark G; Connolly, Denise C; Tchou, Julia; Curiel, Tyler J; Conejo-Garcia, Jose R

    2017-01-15

    To define the safety and effectiveness of T cells redirected against follicle-stimulating hormone receptor (FSHR)-expressing ovarian cancer cells. FSHR expression was determined by Western blotting, immunohistochemistry, and qPCR in 77 human ovarian cancer specimens from 6 different histologic subtypes and 20 human healthy tissues. The effectiveness of human T cells targeted with full-length FSH in vivo was determined against a panel of patient-derived xenografts. Safety and effectiveness were confirmed in immunocompetent tumor-bearing mice, using constructs targeting murine FSHR and syngeneic T cells. FSHR is expressed in gynecologic malignancies of different histologic types but not in nonovarian healthy tissues. Accordingly, T cells expressing full-length FSHR-redirected chimeric receptors mediate significant therapeutic effects (including tumor rejection) against a panel of patient-derived tumors in vivo In immunocompetent mice growing syngeneic, orthotopic, and aggressive ovarian tumors, fully murine FSHR-targeted T cells also increased survival without any measurable toxicity. Notably, chimeric receptors enhanced the ability of endogenous tumor-reactive T cells to abrogate malignant progression upon adoptive transfer into naïve recipients subsequently challenged with the same tumor. Interestingly, FSHR-targeted T cells persisted as memory lymphocytes without noticeable PD-1-dependent exhaustion during end-stage disease, in the absence of tumor cell immunoediting. However, exosomes in advanced tumor ascites diverted the effector activity of this and other chimeric receptor-transduced T cells away from targeted tumor cells. T cells redirected against FSHR + tumor cells with full-length FSH represent a promising therapeutic alternative against a broad range of ovarian malignancies, with negligible toxicity even in the presence of cognate targets in tumor-free ovaries. Clin Cancer Res; 23(2); 441-53. ©2016 AACR. ©2016 American Association for Cancer Research.

  13. CD117 expression in fibroblasts-like stromal cells indicates unfavorable clinical outcomes in ovarian carcinoma patients.

    Directory of Open Access Journals (Sweden)

    Ruixia Huang

    Full Text Available The stem cell factor (SCF receptor CD117 (c-kit, is widely used for identification of hematopoietic stem cells and cancer stem cells. Moreover, CD117 expression in carcinoma cells indicates a poor prognosis in a variety of cancers. However the potential expression in tumor microenvironment and the biological and clinical impact are currently not reported. The expression of CD117 was immunohistochemically evaluated in a serial of 242 epithelial ovarian cancer (EOC cases. Thirty-eight out of 242 cases were CD117 positive in fibroblast-like stromal cells and 22 cases were positive in EOC cells. Four cases were both positive in fibroblast-like stromal cells and EOC cells for CD117. CD117 expression in fibroblast-like stromal cells in ovarian carcinoma was closely linked to advanced FIGO stage, poor differentiation grade and histological subtype (p<0.05, and it was significantly associated with poor overall survival (OS and progression free survival (PFS (Kaplan-Meier analysis; p<0.05, log-rank test. CD117 expression in ovarian carcinoma cells was not associated with these clinicopathological variables. The CD117 positive fibroblast-like stromal cells were all positive for mesenchymal stem/stromal cell (MSC marker CD73 but negative for fibroblast markers fibroblast activation protein (FAP and α smooth muscle actin (α-SMA, indicating that the CD117+/CD73+ fibroblast-like stromal cells are a subtype of mesenchymal stem cells in tumor stroma, although further characterization of these cells are needed. It is concluded herewith that the presence of CD117+/CD73+ fibroblast-like stromal cells in ovarian carcinoma is an unfavorable clinical outcome indication.

  14. Fossil Energy Advanced Research and Technology Development Materials Program. Semiannual progress report for the period ending September 30, 1992

    Energy Technology Data Exchange (ETDEWEB)

    Cole, N.C.; Judkins, R.R. [comps.

    1992-12-01

    Objective of this materials program is to conduct R and D on materials for fossil energy applications with focus on longer-term and generic needs of the various fossil fuel technologies. The projects are organized according to materials research areas: (1) ceramics, (2) new alloys: iron aluminides, advanced austenitics and chromium niobium alloys, and (3) technology development and transfer. Separate abstracts have been prepared.

  15. Tubo-ovarian actinomycosis.

    Directory of Open Access Journals (Sweden)

    Shroff C

    1981-01-01

    Full Text Available Actinomycotic infection of the female genital tract is rare. Actinomycosis is a chronic suppurative granulomatous infection that is characterized by formation of abscesses, multiple draining sinuses and appearance of tangled mycelial masses or granules in the discharges and tissue sections. 2 cases of tubo-ovarian actinomycosis are reported. The 1st case presented clinical with gastrointestinal symptoms and a ventral scar hernia following an operation for a non-healing abdominal wound 6 months earlier. The 2nd case sought medical attention for backache and leucorrhea of 4 years′ duration. Exploratory laparotomy in the 1st case revealed tubo-ovarian masses; the vermiform appendix was not traceable. The uterine cavity in the 2nd case harbored a wooden stick. Direct extension from established ileocacal actinomycosis was believed to involve the female genital adnexae in the past. Association of tubo-ovarian actinomycosis with the presence of a foreign body in the female genital tract has been reported sporadically in the literature, yet an increase in the incidence may be expected because of the frequent use of intrauterine contraceptive devices in recent times. It is suggested that in women presenting clinically with vague abdominal symptoms, backache and discharge, actinomycosis should be considered and ruled out with the help of cytologic and proper microbial culture methods. Once the diagnosis is established, the infection can be treated with good results with penicillin.

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

    Science.gov (United States)

    2018-06-04

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

  17. Acne tarda and male-pattern baldness unmasking primary ovarian insufficiency: a case and review.

    Science.gov (United States)

    Zouboulis, Christos C; Achenbach, Alexander; Makrantonaki, Eugenia

    2014-01-01

    A 30-year-old woman presented with recurrent acne lesions and progressing male-pattern baldness. Furthermore, she reported amenorrhea, weight loss, mucosal xerosis and dyspareunia since discontinuation of hormonal contraception 6 months earlier in order to conceive. Acne tarda and androgenetic alopecia of female pattern were diagnosed. Hormonal and immunologic serological and ultrasound examinations revealed an autoimmune hypergonadotropic primary ovarian insufficiency (POI) with no ovarian cysts but ovarian fibrosis with marked reduced follicle pool. Immediate ovarian stimulation and in vitro fertilization led to pregnancy and the patient gave birth to a healthy child. Though presenting with clinical findings similar to menopause, 50% of patients with POI exhibit varying and unpredictable ovarian function, and only 5-10% are able to accomplish pregnancy. Genetic disorders affect the X chromosome. In 14-30% of cases POI has been associated with autoimmunity. POI may occur after discontinuation of hormonal contraception, like in our case.

  18. Three new genetic loci (R1210C in CFH, variants in COL8A1 and RAD51B are independently related to progression to advanced macular degeneration.

    Directory of Open Access Journals (Sweden)

    Johanna M Seddon

    Full Text Available To assess the independent impact of new genetic variants on conversion to advanced stages of AMD, controlling for established risk factors, and to determine the contribution of genes in predictive models.In this prospective longitudinal study of 2765 individuals, 777 subjects progressed to neovascular disease (NV or geographic atrophy (GA in either eye over 12 years. Recently reported genetic loci were assessed for their independent effects on incident advanced AMD after controlling for 6 established loci in 5 genes, and demographic, behavioral, and macular characteristics. New variants which remained significantly related to progression were then added to a final multivariate model to assess their independent effects. The contribution of genes to risk models was assessed using reclassification tables by determining risk within cross-classified quintiles for alternative models.THREE NEW GENETIC VARIANTS WERE SIGNIFICANTLY RELATED TO PROGRESSION: rare variant R1210C in CFH (hazard ratio (HR 2.5, 95% confidence interval [CI] 1.2-5.3, P = 0.01, and common variants in genes COL8A1 (HR 2.0, 95% CI 1.1-3.5, P = 0.02 and RAD51B (HR 0.8, 95% CI 0.60-0.97, P = 0.03. The area under the curve statistic (AUC was significantly higher for the 9 gene model (.884 vs the 0 gene model (.873, P = .01. AUC's for the 9 vs 6 gene models were not significantly different, but reclassification analyses indicated significant added information for more genes, with adjusted odds ratios (OR for progression within 5 years per one quintile increase in risk score of 2.7, P<0.001 for the 9 vs 6 loci model, and OR 3.5, P<0.001 for the 9 vs. 0 gene model. Similar results were seen for NV and GA.Rare variant CFH R1210C and common variants in COL8A1 and RAD51B plus six genes in previous models contribute additional predictive information for advanced AMD beyond macular and behavioral phenotypes.

  19. [Ovarian cancer. II. Procedures, histology, and complications].

    Science.gov (United States)

    Szpakowski, M; Nowak, M; Malinowski, A; Romanowicz, H; Wieczorek, A; Szpakowski, A; Raczkowska, Z; Władziński, J; Wilczyński, J R; Kamiński, T; Maciołek-Blewniewska, G

    2000-09-01

    The purpose of our study was to analyse the operative procedures and complications in patients operated for the first time for ovarian cancer. A retrospective review of patients' charts with ovarian cancer operated at the Department of Gynaecological Surgery of Polish Mother's Memorial Hospital-Research Institute in 1990-1999 was conducted. We analysed the data of women operated for the first time for this disease. In every case we tried to perform radical operation consisted of hysterectomy with bilateral adnexectomy, omentectomy, appendectomy (if needed), and additionally optimal debulking in advanced cancer. Between January 1990 and December 1999, 107 patients were operated for the first time for ovarian cancer. FIGO staging was as follows: I--13.1%, II--14.95%, III--59.8%, IV--12.15%. The most frequent findings on histology were serous (39.3%), endometrioid (26.2%), undifferentiated (11.2%) and clear cell cancers (10.7%). In 60.7% of cases we performed hysterectomy with bilateral adnexectomy, in 15.0% bilateral adnexectomy, in 4.7% of patients cytoreductive tumorectomy, and in 19.6% of cases only excisions for histology were taken. 69.0% of patients underwent also omentectomy and 42.6% appendectomy. In 58.9% of patients we performed radical operation; its incidence significantly decreased with the increase of FIGO staging: I--100%, II--87.5%, III--51.6%, IV--15.4% (p serous and endometrioid ovarian cancer. The great majority of patients was diagnosed to late and operated in III and IV stage of the disease, but in almost 60% of cases radical operation was performed.

  20. Dexrazoxane Diminishes Doxorubicin-Induced Acute Ovarian Damage and Preserves Ovarian Function and Fecundity in Mice.

    Directory of Open Access Journals (Sweden)

    Jenna Kropp

    Full Text Available Advances in cancer treatment utilizing multiple chemotherapies have dramatically increased cancer survivorship. Female cancer survivors treated with doxorubicin (DXR chemotherapy often suffer from an acute impairment of ovarian function, which can persist as long-term, permanent ovarian insufficiency. Dexrazoxane (Dexra pretreatment reduces DXR-induced insult in the heart, and protects in vitro cultured murine and non-human primate ovaries, demonstrating a drug-based shield to prevent DXR insult. The present study tested the ability of Dexra pretreatment to mitigate acute DXR chemotherapy ovarian toxicity in mice through the first 24 hours post-treatment, and improve subsequent long-term fertility throughout the reproductive lifespan. Adolescent CD-1 mice were treated with Dexra 1 hour prior to DXR treatment in a 1:1 mg or 10:1 mg Dexra:DXR ratio. During the acute injury period (2-24 hours post-injection, Dexra pretreatment at a 1:1 mg ratio decreased the extent of double strand DNA breaks, diminished γH2FAX activation, and reduced subsequent follicular cellular demise caused by DXR. In fertility and fecundity studies, dams pretreated with either Dexra:DXR dose ratio exhibited litter sizes larger than DXR-treated dams, and mice treated with a 1:1 mg Dexra:DXR ratio delivered pups with birth weights greater than DXR-treated females. While DXR significantly increased the "infertility index" (quantifying the percentage of dams failing to achieve pregnancy through 6 gestations following treatment, Dexra pretreatment significantly reduced the infertility index following DXR treatment, improving fecundity. Low dose Dexra not only protected the ovaries, but also bestowed a considerable survival advantage following exposure to DXR chemotherapy. Mouse survivorship increased from 25% post-DXR treatment to over 80% with Dexra pretreatment. These data demonstrate that Dexra provides acute ovarian protection from DXR toxicity, improving reproductive health

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

    Science.gov (United States)

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

    2017-09-01

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

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    Background Niraparib is an oral poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) 1/2 inhibitor that has shown clinical activity in patients with ovarian cancer. We sought to evaluate the efficacy of niraparib versus placebo as maintenance treatment for patients with platinum-sensitive, ......Background Niraparib is an oral poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) 1/2 inhibitor that has shown clinical activity in patients with ovarian cancer. We sought to evaluate the efficacy of niraparib versus placebo as maintenance treatment for patients with platinum...... or 4 adverse events that were reported in the niraparib group were thrombocytopenia (in 33.8%), anemia (in 25.3%), and neutropenia (in 19.6%), which were managed with dose modifications. Conclusions Among patients with platinum-sensitive, recurrent ovarian cancer, the median duration of progression...

  3. 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.

  4. Progress and Lessons Learned in Transuranic Waste Disposition at The Department of Energy's Advanced Mixed Waste Treatment Project

    International Nuclear Information System (INIS)

    J.D. Mousseau; S.C. Raish; F.M. Russo

    2006-01-01

    This paper provides an overview of the Department of Energy's (DOE) Advanced Mixed Waste Treatment Project (AMWTP) located at the Idaho National Laboratory (INL) and operated by Bechtel BWXT Idaho, LLC(BBWI) It describes the results to date in meeting the 6,000-cubic-meter Idaho Settlement Agreement milestone that was due December 31, 2005. The paper further describes lessons that have been learned from the project in the area of transuranic (TRU) waste processing and waste certification. Information contained within this paper would be beneficial to others who manage TRU waste for disposal at the Waste Isolation Pilot Plant (WIPP)

  5. Advanced fuel gas desulfurization (AFGD) demonstration project. Technical progress report No. 19, July 1, 1994--September 30, 1994

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-12-01

    The {open_quotes}Advanced Flue Gas Desulfurization (AFGD) Demonstration Project{close_quotes} is a $150.5 million cooperative effort between the U.S. Department of Energy and Pure Air, a general partnership of Air Products and Chemicals, Inc. and Mitsubishi Heavy Industries America, Inc. The AFGD process is one of several alternatives to conventional flue gas desulfurization (FGD) being demonstrated under the Department of Energy`s Clean Coal Technology Demonstration Program. The AFGD demonstration project is located at the Northern Indiana Public Service Company`s Bailly Generating Station, about 12 miles northeast of Gary, Indiana.

  6. Progress of nuclear safety for symbiosis and sustainability advanced digital instrumentation, control and information systems for nuclear power plants

    CERN Document Server

    Yoshikawa, Hidekazu

    2014-01-01

    This book introduces advanced methods of computational and information systems allowing readers to better understand the state-of-the-art design and implementation technology needed to maintain and enhance the safe operation of nuclear power plants. The subjects dealt with in the book are (i) Full digital instrumentation and control systems and human?machine interface technologies (ii) Risk? monitoring methods for large and? complex? plants (iii) Condition monitors for plant components (iv) Virtual and augmented reality for nuclear power plants and (v) Software reliability verification and val

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

  8. Are ovarian cancer stem cells the target for innovative immunotherapy?

    Directory of Open Access Journals (Sweden)

    Wang L

    2018-05-01

    Full Text Available Liang Wang, Tianmin Xu, Manhua Cui Department of Gynecology and Obstetrics, The Second Hospital of Jilin University, Changchun, Jilin, People’s Republic of China Abstract: Cancer stem cells (CSCs, a subpopulation of cancer cells with the ability of self-renewal and differentiation, are believed to be responsible for tumor generation, progression, metastasis, and relapse. Ovarian cancer, the most malignant gynecological cancer, has consistent pathology behavior with CSC model, which suggests that therapies based on ovarian cancer stem cells (OCSCs can gain a more successful prognosis. Much evidence has proved that epigenetic mechanism played an important role in tumor formation and sustainment. Since CSCs are generally resistant to conventional therapies (chemotherapy and radiotherapy, immunotherapy is a more effective method that has been implemented in the clinic. Chimeric antigen receptor (CAR- T cell, an adoptive cellular immunotherapy, which results in apparent elimination of tumor in both hematologic and solid cancers, could be used for ovarian cancer. This review covers the basic conception of CSCs and OCSCs, the implication of epigenetic mechanism underlying cancer evolution considering CSC model, the immunotherapies reported for ovarian cancer targeting OCSCs currently, and the relationship between immune system and hierarchy cancer organized by CSCs. Particularly, the promising prospects and potential pitfalls of targeting OCSC surface markers to design CAR-T cellular immunotherapy are discussed here. Keywords: cancer stem cells, ovarian cancer, epigenetics, tumor cell surface marker, immunotherapy, CAR

  9. Avelumab (anti-PD-L1) in platinum-resistant/refractory ovarian cancer: JAVELIN Ovarian 200 Phase III study design.

    Science.gov (United States)

    Pujade-Lauraine, Eric; Fujiwara, Keiichi; Dychter, Samuel S; Devgan, Geeta; Monk, Bradley J

    2018-03-27

    Avelumab is a human anti-PD-L1 checkpoint inhibitor with clinical activity in multiple solid tumors. Here, we describe the rationale and design for JAVELIN Ovarian 200 (NCT02580058), the first randomized Phase III trial to evaluate the role of checkpoint inhibition in women with ovarian cancer. This three-arm trial is comparing avelumab administered alone or in combination with pegylated liposomal doxorubicin versus pegylated liposomal doxorubicin alone in patients with platinum-resistant/refractory recurrent ovarian, fallopian tube or peritoneal cancer. Eligible patients are not preselected based on PD-L1 expression and may have received up to three prior lines of chemotherapy for platinum-sensitive disease, but none for resistant disease. Overall survival and progression-free survival are primary end points, and secondary end points include biomarker evaluations and pharmacokinetics.

  10. Genomic and sieroproteomic analysis for the identification of molecular tumor markers for diagnosis, therapy and follow-up of ovarian and endometrial carcinomas

    International Nuclear Information System (INIS)

    Pecorelli, S.

    2009-01-01

    The aim of the study is the identification, through the analysis of genomic and proteomic expression profiles, of novel molecular bio markers correlated with pathogenesis, progression, diagnosis or therapy of ovarian cancer. Patients referring to the Division of Gynecologic Oncology at the University of Brescia have been enrolled in the study starting from April 2007. 66 patients with ovarian carcinoma were included (49 with primary ovarian cancer and 17 with relapse/progression). Controls included 134 patients with histologically proven benign pelvic masses (64 uterine fibromas, 36 benign ovarian cysts, 34 endometriosis). All patients signed an informed consent according to institutional guidelines. Clinico pathological features of patients were collected

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

    NARCIS (Netherlands)

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

    2013-01-01

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

  12. Advanced Gas Cooled Nuclear Reactor Materials Evaluation and Development Program. Progress report, July 1, 1981-September 30, 1981

    International Nuclear Information System (INIS)

    1982-01-01

    Work covered in this report includes the activities associated with the status of the simulated reactor helium supply systems and testing equipment. The progress in the screening test program is described; this includes: screening creep results and metallographic analysis for materials thermally exposed or tested at 750 0 , 850 0 , 950 0 , and 1050 0 C (1382 0 , 1562 0 , 1742 0 , and 1922 0 F). The status of controlled purity helium and air creep-rupture testing in the intensive screening test program is discussed. The results of metallographic studies of screening alloys exposed in controlled purity helium for 3000 hours at 750 0 C and 6000 hours at 850 0 C and for weldments exposed in controlled purity helium for 6000 hours at 850 0 and 950 0 C are presented and discussed

  13. Advanced Researech and Technology Development fossil energy materials program: Semiannual progress report for the period ending September 30, 1988

    Energy Technology Data Exchange (ETDEWEB)

    1989-01-01

    The objective of the ARandTD Fossil Energy Materials Program is to conduct research and development on materials for fossil energy applications with a focus on the longer-term and generic needs of the various fossil fuel technologies. The program includes research aimed toward a better understanding of materials behavior in fossil energy environments and the development of new materials capable of substantial enhancement of plant operations and reliability. The ORNL Fossil Energy Materials Program Office compiles and issues this combined semiannual progress report from camera-ready copies submitted by each of the participating subcontractor organizations. This report of activities on the program is organized in accordance with a work breakdown structure in which projects are organized according to materials research thrust areas. These areas are (1) Structural Ceramics, (2) Alloy Development and Mechanical Properties, (3) Corrosion and Erosion of Alloys, and (4) Assessments and Technology Transfer. Individual projects are processed separately for the data bases.

  14. 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

    2015-12-29

    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.

  15. Primary ovarian insufficiency: an update

    Directory of Open Access Journals (Sweden)

    Cox L

    2014-02-01

    Full Text Available Leticia Cox, James H LiuUH Case Medical Center, MacDonald Women's Hospital, Department of Obstetrics and Gynecology, Case Western Reserve University School of Medicine, Department of Reproductive Biology, Cleveland, OH, USAAbstract: Primary ovarian insufficiency is a condition that represents impaired ovarian function on a continuum with intermittent ovulation. This condition commonly leads to premature menopause, defined as cessation of ovulation prior to the age of 40 years. Because there are potential immediate and long-term consequences of hypoestrogenism, a timely diagnosis is invaluable. This comprehensive review will discuss identifiable causes for primary ovarian insufficiency, including genetic disorders and metabolic abnormalities, as well as review current strategies for diagnosis, evaluation, and management of women with this condition.Keywords: premature ovarian failure, premature menopause, ovarian dysfunction

  16. [Methylation of selected tumor-supressor genes in benign and malignant ovarian tumors].

    Science.gov (United States)

    Cul'bová, M; Lasabová, Z; Stanclová, A; Tilandyová, P; Zúbor, P; Fiolka, R; Danko, J; Visnovský, J

    2011-09-01

    To evaluate the usefullness of examination of methylation status of selected tumor-supressor genes in early diagnosis of ovarian cancer. Prospective clinical study. Department of Gynecology and Obstetrics, Department of Molecular Biology, Jessenius Medical Faculty, Commenius University, Martin, Slovak Republic. In this study we analyzed hypermethylation of 5 genes RASSF1A, GSTP, E-cadherin, p16 and APC in ovarian tumor samples from 34 patients - 13 patients with epithelial ovarian cancer, 2 patients with border-line ovarian tumors, 12 patients with benign lesions of ovaries and 7 patients with healthy ovarian tissue. The methylation status of promoter region of tumor-supressor genes was determined by Methylation Specific Polymerase Chain Reaction (MSP) using a nested two-step approach with bisulfite modified DNA template and specific primers. Gene methylation analysis revealed hypermethylation of gene RASSF1A (46%) and GSTP (8%) only in malignant ovarian tissue samples. Ecad, p16 and APC genes were methylated both in maignant and benign tissue samples. Methylation positivity in observed genes was present independently to all clinical stages of ovarian cancer and to tumor grades. However, there was observed a trend of increased number and selective involvement of methylated genes with increasing disease stages. Furthermore, there was no association between positive methylation status and histological subtypes of ovarian carcinomas. RASSF1A and GSTP promoter methylation positivity is associated with ovarian cancer. The revealed gene-selective methylation positivity and the increased number of methylated genes with advancing disease stages could be considered as a useful molecular marker for early detection of ovarian cancer. However, there is need to find diagnostic approach of specifically and frequently methylated genes to determining a methylation phenotype for early detection of ovarian malignancies.

  17. [Engineering development of advanced coal-fired low-emission boiler systems]. Technical progress report, October--December 1995

    Energy Technology Data Exchange (ETDEWEB)

    Wesnor, J.D.; Bakke, E. [ABB Environmental Systems, Birmingham, AL (United States); Bender, D.J.; Kaminski, R.S. [Raytheon Engineers and Constructors, Inc., Philadelphia, PA (United States)

    1995-12-31

    The overall objective of the Project is the expedited commercialization of advanced coal-fired low-emisssion boiler systems. The primary objectives are: NO{sub x} emissions, lb/million Btu; SO{sub 2} emissions, lb/million Btu; particulate emissions, lb/million Btu; and net plant efficiency, not less than 42%. The secondary objectives are: improved ash disposability; reduced waste generation; and reduced air toxics emissions. Accomplishments to date are summarized for the following tasks: task 1, project planning and management; task 7, component development and optimization; task 8, preliminary POC test facility design; task 9, subsystem test design and plan; task 10, subsystem test unit construction; and task 11, subsystem test operation and evaluation.

  18. Advanced Technology and Mitigation (ATDM) SPARC Re-Entry Code Fiscal Year 2017 Progress and Accomplishments for ECP.

    Energy Technology Data Exchange (ETDEWEB)

    Crozier, Paul [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Howard, Micah [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Rider, William J. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Freno, Brian Andrew [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Bova, Steven W. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Carnes, Brian [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2017-09-01

    The SPARC (Sandia Parallel Aerodynamics and Reentry Code) will provide nuclear weapon qualification evidence for the random vibration and thermal environments created by re-entry of a warhead into the earth’s atmosphere. SPARC incorporates the innovative approaches of ATDM projects on several fronts including: effective harnessing of heterogeneous compute nodes using Kokkos, exascale-ready parallel scalability through asynchronous multi-tasking, uncertainty quantification through Sacado integration, implementation of state-of-the-art reentry physics and multiscale models, use of advanced verification and validation methods, and enabling of improved workflows for users. SPARC is being developed primarily for the Department of Energy nuclear weapon program, with additional development and use of the code is being supported by the Department of Defense for conventional weapons programs.

  19. Pediatric ovarian torsion: an uncommon clinical entity

    OpenAIRE

    Rajwani, Kapil M; Mahomed, Anies

    2014-01-01

    Key Clinical Message Pediatric ovarian torsion is an infrequent diagnosis and it often mimics acute appendicitis. Most cases are due to underlying ovarian pathology and if left untreated, ovarian torsion may eventually cause peritonitis. Emergency exploratory laparoscopy represents a valuable diagnostic and therapeutic tool in suspected ovarian torsion.

  20. History of thyroid disease and survival of ovarian cancer patients: results from the Ovarian Cancer Association Consortium, a brief report.

    Science.gov (United States)

    Minlikeeva, Albina N; Freudenheim, Jo L; Cannioto, Rikki A; Eng, Kevin H; Szender, J Brian; Mayor, Paul; Etter, John L; Cramer, Daniel W; Diergaarde, Brenda; Doherty, Jennifer A; Dörk, Thilo; Edwards, Robert; deFazio, Anna; Friel, Grace; Goodman, Marc T; Hillemanns, Peter; Høgdall, Estrid; Jensen, Allan; Jordan, Susan J; Karlan, Beth Y; Kjær, Susanne K; Klapdor, Rüdiger; Matsuo, Keitaro; Mizuno, Mika; Nagle, Christina M; Odunsi, Kunle; Paddock, Lisa; Rossing, Mary Anne; Schildkraut, Joellen M; Schmalfeldt, Barbara; Segal, Brahm H; Starbuck, Kristen; Terry, Kathryn L; Webb, Penelope M; Zsiros, Emese; Ness, Roberta B; Modugno, Francesmary; Bandera, Elisa V; Chang-Claude, Jenny; Moysich, Kirsten B

    2017-09-26

    Findings from in vitro studies suggest that increased exposure to thyroid hormones can influence progression of ovarian tumours. However, epidemiologic evidence on this topic is limited. We pooled data from 11 studies from the Ovarian Cancer Association Consortium. Using multivariate Cox proportional hazards models, we estimated associations between hyper- and hypothyroidism and medications prescribed for these conditions with 5-year all-cause survival among women diagnosed with invasive ovarian cancer. Overall, there was a nonsignificant association with history of hyperthyroidism (n=160 cases) and mortality (HR=1.22; 95% CI=0.97-1.53). Furthermore, diagnosis of hyperthyroidism within the 5 years before ovarian cancer diagnosis was associated with an increased risk of death (HR=1.94; 95% CI=1.19-3.18). A more modest association was observed with history of hypothyroidism (n=624 cases) and mortality (HR=1.16; 95% CI=1.03-1.31). Neither duration of hypothyroidism nor use of thyroid medications was associated with survival. In this large study of women with ovarian cancer, we found that recent history of hyperthyroidism and overall history of hypothyroidism were associated with worse 5-year survival.

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

    Science.gov (United States)

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

    2017-09-01

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

  2. Endometriosis and Ovarian Cancer: A Review of Clinical, Pathologic, and Molecular Aspects

    Science.gov (United States)

    Wei, Jian-Jun; William, Josette; Bulun, Serdar

    2014-01-01

    Summary Endometriosis is a chronic disease that affects millions of reproductive-age women. Despite the destructive and invasive nature of endometrioses, most cases are perpetually benign or eventually regress; however, atypical endometriosis is a precursor lesion and can lead to certain types of ovarian cancer. Endometriosis induced inflammation and auto- and paracrine production of sex steroid hormones contribute to ovarian tumorigenesis. These changes provide microenvironment necessary to accumulate enough genetic alterations for endometriosis associated malignant transformation. It takes years for endometriosis to undergo the pathophysiological progression that begins with atypical epithelial proliferation (atypical endometriosis and metaplasia), and then is followed by the formation of well-defined borderline tumors, and finally culminates in fully malignant ovarian cancer. This study is a review of the natural history of endometriosis and the role of microenvironments that favor the accumulation of genetic alterations and endometriosis-associated ovarian cancer progression. PMID:21979592

  3. Struma ovarii mimicking ovarian carcinoma: a case report and review of the literature

    Energy Technology Data Exchange (ETDEWEB)

    Landim, Fabio Machado [Hospital Geral Doutor Waldemar de Alcantara, Fortaleza, CE (Brazil)

    2008-07-01

    Struma Ovarii is a rare neoplasia. It is a monodermic mixed teratoma, with predominance of thyroid tissue and represents 3% of ovarian teratomas. This article reports a case of Struma Ovarii in a 66 years-old patient, with a progressive abdominal mass, ascites and high levels of CA-125. The findings were highly suggestive of ovarian carcinoma. The CT scan showed a complex ovarian lesion and the patient was submitted to an exploratory laparotomy. The pathology report showed a left ovary Struma Ovarii. (author)

  4. Prognostic and clinicopathological significance of Cacna2d1 expression in epithelial ovarian cancers: a retrospective study

    Science.gov (United States)

    Yu, Dandan; Holm, Ruth; Goscinski, Mariusz Adam; Trope, Claes G; Nesland, Jahn M; Suo, Zhenhe

    2016-01-01

    Ovarian cancer is the most lethal gynecologic malignancy, in which cancer stem cells (CSC) have been reported to be the driving force of relapse and therapy-resistance. It is therefore important to explore CSC markers in ovarian cancer. This project aimed to explore the correlation between the expression of potential CSC maker Cacna2d1 and clinicopathological parameters in 238 epithelial ovarian cancer (EOC) samples. Immunohistochemically, positive Cacna2d1 expression was observed in 83.6% (199/238) of the EOC tumors, among which 107 tumors (44.9%) were highly positive and 92 (38.7%) tumors were weakly positive for the Cacna2d1 protein expression. Among the 158 serous carcinomas, the Cacna2d1 positivity was 148 (93.7%), in which 88 (55.7%) were highly positive, and 60 (38.0%) were weakly positive for the Cacna2d1 protein expression. Most strikingly, the Cacna2d1 was specifically expressed in the infiltration front areas of the EOC tumors. Statistical analyses showed that positive expression of Cacna2d1 was significantly associated with advanced FIGO stage (P<0.001), histological subtype (P=0.017) and tumor differentiation (P=0.015). Positive Cacna2d1 protein expression was significantly associated with poor overall survival (OS) and shorter progression free survival (PFS) in both total EOCs and serous carcinomas, although multivariate analyses did not reach statistical significance. In summary, our results suggest Cacna2d1 protein may play a crucial role in promoting aggressive EOC behavior and progression, and Cacna2d1 may serve as a novel predictive prognostic marker and a potential target for therapeutic intervention in EOCs. PMID:27725913

  5. Individualized controlled ovarian stimulation in expected poor-responders: an update.

    Science.gov (United States)

    Haahr, Thor; Esteves, Sandro C; Humaidan, Peter

    2018-03-09

    Controlled ovarian stimulation with subsequent multi-follicular development continues to be a keystone in ART. Evidence supports an individualized approach to ovarian stimulation, usually involving combinations of ovarian reserve tests, body mass index and age to tailor the exogenous gonadotropin dose, and potentially adjuvant treatment aiming for high safety and a shortening of time to live birth. While stimulation and trigger concepts have been developed successfully in normo- and hyperresponder patients, the poor responder patient remains difficult to manage. However, recent advances in definition and classification of the expected poor ovarian responder patient might enable a more accurate and clinically useful interpretation of new treatment concepts in a more homogenous study population. In the present review, we discuss the classification of the expected poor ovarian responder patient as well as clinically useful measurements of efficacy for controlled ovarian stimulation, and finally, we discuss the evidence for clinical management of patients with expected poor ovarian response, including adjuvant treatments such as growth hormone, androgens, and LH activity.In conclusion, the best available evidence supports that the treatment of the expected poor ovarian response patient should be individualized in all steps of ART, including the choice of GnRH analogue, the gonadotropin type and dose, ovulation trigger, and the possible use of adjuvant therapies.

  6. Advanced Gas Cooled Nuclear Reactor Materials Evaluation and Development Program. Progress report, July 1, 1980-September 30, 1980

    International Nuclear Information System (INIS)

    1980-01-01

    Objectives of this program are to evaluate candidate alloys for Very High Temperature Reactor (VHTR) Nuclear Process Heat (NPH) and Direct Cycle Helium Turbine (DCHT) applications, in terms of the effect of simulated reactor primary coolant (helium containing small amounts of various other gases), high temperatures, and long time exposures, on the mechanical properties and structural and surface stability of selected candidate alloys. A second objective is to select and recommend materials for future test facilities and more extensive qualification programs. Work covered in this report includes the activities associated with the status of the simulated reactor helium supply system, testing equipment and gas chemistry analysis instrumentation and equipment. The progress in the screening test program is described: screening creep results and metallographic analysis for materials thermally exposed or tested at 750, 850, 950 and 1050 0 C. Initiation of controlled purity helium creep-rupture testing in the intensive screening test program is discussed. In addition, the results of 1000-hour exposures at 750 and 850 0 C on several experimental alloys are discussed

  7. Ultrasonography of ovarian hyperandrogenemia

    Science.gov (United States)

    Kuzmina, Svetlana A.; Zharkin, Nikolay A.

    2001-05-01

    The method of ultrasonography is high informative and widely used in diagnostics of ovarian hyperandrogenaemia. The majority of authors consider that a hyperplasia of a stroma is the main pathognomonic marker of polycystic ovaries (PCO). Still recently swell of a stroma was valued visually, that had subjective nature. We offer for the first time a way of diagnostics of stromal hyperplasia grounded on measurement of a volume of a stroma and ovary with ultrasound method, calculation of the ratio of a volume of the ovary to a volume of a stroma for every patient.

  8. Role of PELP1 in EGFR-ER Signaling Crosstalk in Ovarian Cancer Cells

    Science.gov (United States)

    2009-04-01

    expression of genes involved in metastasis using a focused microarray approach. We have used Human Tumor Metastasis Microarray (Oligo GE array from...ovarian cancer progression. Analysis of human genome databases and SAGE data suggested deregulation of PELP1 expression in ovarian cancer cells...PI3K, and STAT3 in the cytosol. PELP1/MNAR regulates meiosis via its interactions with heterotimeric Gbc protein, androgen receptor (AR), and by

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

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  10. Fertility drugs and ovarian cancer.

    Science.gov (United States)

    Ali, Aus Tariq

    2017-06-20

    The aetiology of ovarian cancer is multifactorial with both endogenous and exogenous risk factors playing an important role. The exact pathogenesis of ovarian cancer is still not well understood, despite the number of hypotheses published. Due to an increase in the number of women using fertility drugs, much attention has been focused on the long-term health effects of such drugs. Although fertility drugs facilitate the ovulation process, it is however associated with a significant increase in hormone concentrations, placing exposed women at increased risk of gynaecological cancer. Many clinical and epidemiological studies have examined the association between fertility drugs and ovarian cancer risk. Results from these studies have been contradictory, as some studies have reported an increased risk of ovarian cancer while others reported no increased risk. Nevertheless, recent studies have shown that women who used fertility drugs and did not conceive had a higher risk of developing ovarian cancer, compared to women who used fertility drugs and conceived and delivered successfully. This review discusses the effect of fertility drugs on the risk of developing ovarian cancer, providing details on four possible scenarios associated with fertility treatment. In addition, the limitations of previous studies and their impact on our understanding of the association between fertility drugs and ovarian cancer also have been highlighted. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. A phase I clinical trial of adoptive transfer of folate receptor-alpha redirected autologous T cells for recurrent ovarian cancer

    Directory of Open Access Journals (Sweden)

    Kandalaft Lana E

    2012-08-01

    Full Text Available Abstract Purpose In spite of increased rates of complete response to initial chemotherapy, most patients with advanced ovarian cancer relapse and succumb to progressive disease. Rationale Genetically reprogrammed, patient-derived chimeric antigen receptor (CAR-T lymphocytes with the ability to recognize predefined surface antigens with high specificity in a non-MHC restricted manner have shown increasing anti-tumor efficacy in preclinical and clinical studies. Folate receptor-α (FRα is an ovarian cancer-specific tumor target; however, it is expressed at low levels in certain organs with risk for toxicity. Design Here we propose a phase I study testing the feasibility, safety and preliminary activity of FRα-redirected CAR-T cells bearing the CD137 (4-1BB costimulatory domain, administered after lymphodepletion for the treatment of recurrent ovarian cancer. A novel trial design is proposed that maximizes safety features. Innovation This design involves an initial accelerated dose escalation phase of FR-α CAR-T cells followed by a standard 3 + 3 escalation phase. A split-dose approach is proposed to mitigate acute adverse events. Furthermore, infusion of bulk untransduced autologous peripheral blood lymphocytes (PBL is proposed two days after CAR-T cell infusion at the lower dose levels of CAR-T cells, to suppress excessive expansion of CAR-T cells in vivo and mitigate toxicity.

  12. Progress in Methodologies for the Assessment of Passive Safety System Reliability in Advanced Reactors. Results from the Coordinated Research Project on Development of Advanced Methodologies for the Assessment of Passive Safety Systems Performance in Advanced Reactors

    International Nuclear Information System (INIS)

    2014-09-01

    Strong reliance on inherent and passive design features has become a hallmark of many advanced reactor designs, including several evolutionary designs and nearly all advanced small and medium sized reactor (SMR) designs. Advanced nuclear reactor designs incorporate several passive systems in addition to active ones — not only to enhance the operational safety of the reactors but also to eliminate the possibility of serious accidents. Accordingly, the assessment of the reliability of passive safety systems is a crucial issue to be resolved before their extensive use in future nuclear power plants. Several physical parameters affect the performance of a passive safety system, and their values at the time of operation are unknown a priori. The functions of passive systems are based on basic physical laws and thermodynamic principals, and they may not experience the same kind of failures as active systems. Hence, consistent efforts are required to qualify the reliability of passive systems. To support the development of advanced nuclear reactor designs with passive systems, investigations into their reliability using various methodologies are being conducted in several Member States with advanced reactor development programmes. These efforts include reliability methods for passive systems by the French Atomic Energy and Alternative Energies Commission, reliability evaluation of passive safety system by the University of Pisa, Italy, and assessment of passive system reliability by the Bhabha Atomic Research Centre, India. These different approaches seem to demonstrate a consensus on some aspects. However, the developers of the approaches have been unable to agree on the definition of reliability in a passive system. Based on these developments and in order to foster collaboration, the IAEA initiated the Coordinated Research Project (CRP) on Development of Advanced Methodologies for the Assessment of Passive Safety Systems Performance in Advanced Reactors in 2008. The

  13. Engineered gold nanoparticles for identification of novel ovarian biomarkers

    Science.gov (United States)

    Giri, Karuna

    multiple proteins not detected by mass spectrometry alone. Differential expression analysis of proteins in cancer vs. non-cancer cells identified many proteins exclusively expressed in ovarian cancer. Hepatoma derived growth factor (HDGF) was one of the identified proteins that became the focus of the second part of the study. Understanding the role of HDGF in ovarian cancer would uncover its potential as a diagnostic and/or therapeutic marker. HDGF was found to be overexpressed in multiple ovarian cancer cell lines and xenograft models of ovarian cancer. Intracellular HDGF promoted cell proliferation, cell cycle progression and survival of ovarian cancer cell lines. While HDGF was exclusively localized in the nucleus, the protein was passively released from ovarian non-cancer and cancer cells during late apoptosis and necrosis. Extracellular HDGF activated MAP kinase pathways through a yet unknown receptor and promoted cell migration. Overall, the results presented in this study provide considerable support for the use of AuNPs for protein enrichment and detection of low abundance proteins. The functional study of HDGF, which revealed the importance of its expression in cancer cell, provides additional validation for AuNPs based cancer biomarker discovery. Further studies regarding the release of HDGF by cancer cells will help evaluate its utility in detecting and monitoring ovarian cancer. Additionally, initial results with knock down experiments indicate that HDGF has the potential to be a therapeutic target for inhibition of cancer progression.

  14. Paternal lineage early onset hereditary ovarian cancers: A Familial Ovarian Cancer Registry study.

    Directory of Open Access Journals (Sweden)

    Kevin H Eng

    2018-02-01

    Full Text Available Given prior evidence that an affected woman conveys a higher risk of ovarian cancer to her sister than to her mother, we hypothesized that there exists an X-linked variant evidenced by transmission to a woman from her paternal grandmother via her father. We ascertained 3,499 grandmother/granddaughter pairs from the Familial Ovarian Cancer Registry at the Roswell Park Cancer Institute observing 892 informative pairs with 157 affected granddaughters. We performed germline X-chromosome exome sequencing on 186 women with ovarian cancer from the registry. The rate of cancers was 28.4% in paternal grandmother/granddaughter pairs and 13.9% in maternal pairs consistent with an X-linked dominant model (Chi-square test X2 = 0.02, p = 0.89 and inconsistent with an autosomal dominant model (X2 = 20.4, p<0.001. Paternal grandmother cases had an earlier age-of-onset versus maternal cases (hazard ratio HR = 1.59, 95%CI: 1.12-2.25 independent of BRCA1/2 status. Reinforcing the X-linked hypothesis, we observed an association between prostate cancer in men and ovarian cancer in his mother and daughters (odds ratio, OR = 2.34, p = 0.034. Unaffected mothers with affected daughters produced significantly more daughters than sons (ratio = 1.96, p<0.005. We performed exome sequencing in reported BRCA negative cases from the registry. Considering age-of-onset, one missense variant (rs176026 in MAGEC3 reached chromosome-wide significance (Hazard ratio HR = 2.85, 95%CI: 1.75-4.65 advancing the age of onset by 6.7 years. In addition to the well-known contribution of BRCA, we demonstrate that a genetic locus on the X-chromosome contributes to ovarian cancer risk. An X-linked pattern of inheritance has implications for genetic risk stratification. Women with an affected paternal grandmother and sisters of affected women are at increased risk for ovarian cancer. Further work is required to validate this variant and to characterize carrier families.

  15. The influence of sarcopenia on survival and surgical complications in ovarian cancer patients undergoing primary debulking surgery

    NARCIS (Netherlands)

    Rutten, I.J.; Ubachs, J.; Kruitwagen, R.F.P.M.; Dijk, D.P. van; Beets-Tan, R.G.; Massuger, L.F.A.G.; Oude Damink, S.W.; Gorp, T. Van

    2017-01-01

    BACKGROUND: Sarcopenia, severe skeletal muscle loss, has been identified as a prognostic factor in various malignancies. This study aims to investigate whether sarcopenia is associated with overall survival (OS) and surgical complications in patients with advanced ovarian cancer undergoing primary

  16. Novel near-diploid ovarian cancer cell line derived from a highly aneuploid metastatic ovarian tumor.

    Directory of Open Access Journals (Sweden)

    Ester Rozenblum

    Full Text Available A new ovarian near-diploid cell line, OVDM1, was derived from a highly aneuploid serous ovarian metastatic adenocarcinoma. A metastatic tumor was obtained from a 47-year-old Ashkenazi Jewish patient three years after the first surgery removed the primary tumor, both ovaries, and the remaining reproductive organs. OVDM1 was characterized by cell morphology, genotyping, tumorigenic assay, mycoplasma testing, spectral karyotyping (SKY, and molecular profiling of the whole genome by aCGH and gene expression microarray. Targeted sequencing of a panel of cancer-related genes was also performed. Hierarchical clustering of gene expression data clearly confirmed the ovarian origin of the cell line. OVDM1 has a near-diploid karyotype with a low-level aneuploidy, but samples of the original metastatic tumor were grossly aneuploid. A number of single nucleotide variations (SNVs/mutations were detected in OVDM1 and the metastatic tumor samples. Some of them were cancer-related according to COSMIC and HGMD databases (no founder mutations in BRCA1 and BRCA2 have been found. A large number of focal copy number alterations (FCNAs were detected, including homozygous deletions (HDs targeting WWOX and GATA4. Progression of OVDM1 from early to late passages was accompanied by preservation of the near-diploid status, acquisition of only few additional large chromosomal rearrangements and more than 100 new small FCNAs. Most of newly acquired FCNAs seem to be related to localized but massive DNA fragmentation (chromothripsis-like rearrangements. Newly developed near-diploid OVDM1 cell line offers an opportunity to evaluate tumorigenesis pathways/events in a minor clone of metastatic ovarian adenocarcinoma as well as mechanisms of chromothripsis.

  17. Ovarian size and response to laparoscopic ovarian electro-cauterization in polycystic ovarian disease.

    Science.gov (United States)

    Alborzi, S; Khodaee, R; Parsanejad, M E

    2001-09-01

    To evaluate endocrine and ovulatory changes in polycystic ovarian disease (PCOD) in relation to patients' ovarian size. Three hundred and seventy-one women with clomiphene citrate-resistant PCOD underwent laparoscopic ovarian cauterization [type I or typical with ovarian volume >8 cm(3) or cross-sectional area >10 cm(2) (n=211), type II with normal size ovary (n=160)]. Serum levels of LH, FSH, DHEAS, PRL, and T before and 10 days after ovarian cautery, spontaneous and induced ovulation and pregnancy rates were compared. Both groups responded to therapy in a similar manner, with a marked decrease in LH, FSH, DHEAS and T levels, with ovulation rates in type I 90.99%, type II 88.75% and pregnancy rates, 73.45% and 71.25%, respectively, with no statistical differences. Hormonal changes, ovulation and pregnancy rates were similar in the two types of PCOD, therefore it can be concluded that ovarian size is not a prognostic factor for response of PCOD patients to laparoscopic ovarian electro-cauterization.

  18. Epigenetic down-regulated DDX10 promotes cell proliferation through Akt/NF-κB pathway in ovarian cancer

    Energy Technology Data Exchange (ETDEWEB)

    Gai, Muhuizi; Bo, Qifang; Qi, Lixia, E-mail: lixiaqi_dph@sina.com

    2016-01-22

    Ovarian cancer contributes to the majority of ovarian cancer, while the molecular mechanisms remain elusive. Recently, some DEAD box protein 1 has been reported play a tumor suppressor role in ovarian cancer progression. However, the functions of DEAD box protein (DDX) members in ovarian cancer development remain largely unknown. In current study, we retrieved GEO databases and surprisingly found that DDX10 is significantly down-regulated in ovarian cancer tissues compared with normal ovary. These findings suggest that DDX10 might also play a suppressive role in ovarian cancer. We then validated the down-regulated expression pattern of DDX10 in fresh ovarian cancer tissues. Furthermore, both loss- and gain-functions assays reveal that the down-regulated DDX10 could promote ovarian cancer proliferation in vitro and the xenograft subcutaneous tumor formation assays confirmed these findings in vivo. In addition, we found that DDX10 is epigenetic silenced by miR-155-5p in ovarian cancer. Moreover, we further preliminary illustrated that down-regulated DDX10 promotes ovarian cancer cell proliferation through Akt/NF-κB pathway. Taken together, in current study, we found a novel tumor suppressor, DDX10, is epigenetic silenced by miR-155-5p in ovarian cancer, and the down-regulated expression pattern of DDX10 promotes ovarian cancer proliferation through Akt/NF-κB pathway. Our findings shed the light that DDX families might be a novel for ovarian cancer treatment. - Highlights: • A novel DEAD box protein, DDX10 is significantly down-regulated in ovarian cancer tissues. • Down-regulated DDX10 promotes ovarian cancer cell proliferation and growth both in vitro and in vivo. • miR-155-5p is highly expressed in ovarian cancer tissues and epigenetically targets DDX10. • DDX10 and miR-155-5p regulates Akt/p65 axis in ovarian cancer cells.

  19. Epigenetic down-regulated DDX10 promotes cell proliferation through Akt/NF-κB pathway in ovarian cancer

    International Nuclear Information System (INIS)

    Gai, Muhuizi; Bo, Qifang; Qi, Lixia

    2016-01-01

    Ovarian cancer contributes to the majority of ovarian cancer, while the molecular mechanisms remain elusive. Recently, some DEAD box protein 1 has been reported play a tumor suppressor role in ovarian cancer progression. However, the functions of DEAD box protein (DDX) members in ovarian cancer development remain largely unknown. In current study, we retrieved GEO databases and surprisingly found that DDX10 is significantly down-regulated in ovarian cancer tissues compared with normal ovary. These findings suggest that DDX10 might also play a suppressive role in ovarian cancer. We then validated the down-regulated expression pattern of DDX10 in fresh ovarian cancer tissues. Furthermore, both loss- and gain-functions assays reveal that the down-regulated DDX10 could promote ovarian cancer proliferation in vitro and the xenograft subcutaneous tumor formation assays confirmed these findings in vivo. In addition, we found that DDX10 is epigenetic silenced by miR-155-5p in ovarian cancer. Moreover, we further preliminary illustrated that down-regulated DDX10 promotes ovarian cancer cell proliferation through Akt/NF-κB pathway. Taken together, in current study, we found a novel tumor suppressor, DDX10, is epigenetic silenced by miR-155-5p in ovarian cancer, and the down-regulated expression pattern of DDX10 promotes ovarian cancer proliferation through Akt/NF-κB pathway. Our findings shed the light that DDX families might be a novel for ovarian cancer treatment. - Highlights: • A novel DEAD box protein, DDX10 is significantly down-regulated in ovarian cancer tissues. • Down-regulated DDX10 promotes ovarian cancer cell proliferation and growth both in vitro and in vivo. • miR-155-5p is highly expressed in ovarian cancer tissues and epigenetically targets DDX10. • DDX10 and miR-155-5p regulates Akt/p65 axis in ovarian cancer cells.

  20. Ovarian cancer clinical trial endpoints: Society of Gynecologic Oncology white paper

    Science.gov (United States)

    Herzog, Thomas J.; Armstrong, Deborah K.; Brady, Mark F.; Coleman, Robert L.; Einstein, Mark H.; Monk, Bradley J.; Mannel, Robert S.; Thigpen, J. Tate; Umpierre, Sharee A.; Villella, Jeannine A.; Alvarez, Ronald D.

    2015-01-01

    Objective To explore the value of multiple clinical endpoints in the unique setting of ovarian cancer. Methods A clinical trial workgroup was established by the Society of Gynecologic Oncology to develop a consensus statement via multiple conference calls, meetings and white paper drafts. Results Clinical trial endpoints have profound effects on late phase clinical trial design, result interpretation, drug development, and regulatory approval of therapeutics. Selection of the optimal clinical trial endpoint is particularly provocative in ovarian cancer where long overall survival (OS) is observed. The lack of new regulatory approvals and the lack of harmony between regulatory bodies globally for ovarian cancer therapeutics are of concern. The advantages and disadvantages of the numerous endpoints available are herein discussed within the unique context of ovarian cancer where both crossover and post-progression therapies potentially uncouple surrogacy between progression-free survival (PFS) and OS, the two most widely supported and utilized endpoints. The roles of patient reported outcomes (PRO) and health related quality of life (HRQoL) are discussed, but even these widely supported parameters are affected by the unique characteristics of ovarian cancer where a significant percentage of patients may be asymptomatic. Original data regarding the endpoint preferences of ovarian cancer advocates is presented. Conclusions Endpoint selection in ovarian cancer clinical trials should reflect the impact on disease burden and unique characteristics of the treatment cohort while reflecting true patient benefit. Both OS and PFS have led to regulatory approvals and are clinically important. OS remains the most objective and accepted endpoint because it is least vulnerable to bias; however, the feasibility of OS in ovarian cancer is compromised by the requirement for large trial size, prolonged time-line for final analysis, and potential for unintended loss of treatment effect

  1. Ovarian cancer clinical trial endpoints: Society of Gynecologic Oncology white paper.

    Science.gov (United States)

    Herzog, Thomas J; Armstrong, Deborah K; Brady, Mark F; Coleman, Robert L; Einstein, Mark H; Monk, Bradley J; Mannel, Robert S; Thigpen, J Tate; Umpierre, Sharee A; Villella, Jeannine A; Alvarez, Ronald D

    2014-01-01

    To explore the value of multiple clinical endpoints in the unique setting of ovarian cancer. A clinical trial workgroup was established by the Society of Gynecologic Oncology to develop a consensus statement via multiple conference calls, meetings and white paper drafts. Clinical trial endpoints have profound effects on late phase clinical trial design, result interpretation, drug development, and regulatory approval of therapeutics. Selection of the optimal clinical trial endpoint is particularly provocative in ovarian cancer where long overall survival (OS) is observed. The lack of new regulatory approvals and the lack of harmony between regulatory bodies globally for ovarian cancer therapeutics are of concern. The advantages and disadvantages of the numerous endpoints available are herein discussed within the unique context of ovarian cancer where both crossover and post-progression therapies potentially uncouple surrogacy between progression-free survival (PFS) and OS, the two most widely supported and utilized endpoints. The roles of patient reported outcomes (PRO) and health related quality of life (HRQoL) are discussed, but even these widely supported parameters are affected by the unique characteristics of ovarian cancer where a significant percentage of patients may be asymptomatic. Original data regarding the endpoint preferences of ovarian cancer advocates is presented. Endpoint selection in ovarian cancer clinical trials should reflect the impact on disease burden and unique characteristics of the treatment cohort while reflecting true patient benefit. Both OS and PFS have led to regulatory approvals and are clinically important. OS remains the most objective and accepted endpoint because it is least vulnerable to bias; however, the feasibility of OS in ovarian cancer is compromised by the requirement for large trial size, prolonged time-line for final analysis, and potential for unintended loss of treatment effect from active post-progression therapies

  2. Regulation of semaphorin 4D expression and cell proliferation of ovarian cancer by ERalpha and ERbeta

    Directory of Open Access Journals (Sweden)

    Y. Liu

    Full Text Available Ovarian cancer is one of the most common malignancies in women. Semaphorin 4D (sema 4D is involved in the progress of multiple cancers. In the presence of estrogen-like ligands, estrogen receptors (ERα and ERβ participate in the progress of breast and ovarian cancers by transcriptional regulation. The aim of the study was to investigate the role of sema 4D and elucidate the regulatory pattern of ERα and ERβ on sema 4D expression in ovarian cancers. Sema 4D levels were up-regulated in ovarian cancer SKOV-3 cells. Patients with malignant ovarian cancers had significantly higher sema 4D levels than controls, suggesting an oncogene role of sema 4D in ovarian cancer. ERα expressions were up-regulated in SKOV-3 cells compared with normal ovarian IOSE80 epithelial cells. Conversely, down-regulation of ERβ was observed in SKOV-3 cells. Forced over-expression of ERα and ERβ in SKOV-3 cells was manipulated to establish ERα+ and ERβ+ SKOV-3 cell lines. Incubation of ERα+ SKOV-3 cells with ERs agonist 17β-estradiol (E2 significantly enhanced sema 4D expression and rate of cell proliferation. Incubated with E2, ERβ+ SKOV-3 cells showed lower sema 4D expression and cell proliferation. Blocking ERα and ERβ activities with ICI182-780 inhibitor, sema 4D expressions and cell proliferation of ERα+ and ERβ+ SKOV-3 cells were recovered to control levels. Taken together, the data showed that sema 4D expression was positively correlated with the progress of ovarian cancer. ERα positively regulated sema 4D expression and accelerated cell proliferation. ERβ negatively regulated sema 4D expression and inhibited cell multiplication.

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

    NARCIS (Netherlands)

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

    2017-01-01

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

  4. Epigenetic Characterization of Ovarian Cancer

    National Research Council Canada - National Science Library

    Murphy, Susan K

    2005-01-01

    .... The approach is to use normal ovarian surface epithelium (NOSE) and malignant cells obtained directly from surgically removed specimens in order to most closely approximate the methylation status in vivo...

  5. 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.

  6. Ovarian torsion: Echographic discoveries

    International Nuclear Information System (INIS)

    Triana R, Gustavo; Navas O, Claudia

    1994-01-01

    Patient of 31 years who consulted to the even service of urgencies to present of two hours of evolution intense pain in flank and region lumbar left, associated to vomit, present square similar 5 previous days to the entrance in the right side. Go Po, plans with DIU FUR, 8 previous days to the square. It is practiced Tran abdominal pelvic echography that shows left ovary of 6 x 5 x 3 cms, with multiple follicular images, of thick walls, with I liquidate free abdominal, highly suggestive of ovarian torsion although the patient didn't present square of sharp abdomen. It decides to suspend analgesic and to value it, presented sharp abdominal pain, reason why laparotomy was practiced, finding mass of 6 x 6 cms. of necrotic aspect, corresponding to the left ovary, which presented three turns on their axis. It is taken finish left salpingooferectomy

  7. Polycystic ovarian syndrome

    Directory of Open Access Journals (Sweden)

    Nina Madnani

    2013-01-01

    Full Text Available Polycystic ovarian syndrome (PCOS is a "multispeciality" disorder suspected in patients with irregular menses and clinical signs of hyperandrogenism such as acne, seborrhoea, hirsutism, irregular menses, infertility, and alopecia. Recently, PCOS has been associated with the metabolic syndrome. Patients may develop obesity, insulin resistance, acanthosis nigricans, Type 2 diabetes, dyslipidemias, hypertension, non-alcoholic liver disease, and obstructive sleep apnoea. Good clinical examination with hematological and radiological investigations is required for clinical evaluation. Management is a combined effort involving a dermatologist, endocrinologist, gynecologist, and nutritionist. Morbidity in addition includes a low "self image" and poor quality of life. Long term medications and lifestyle changes are essential for a successful outcome. This article focuses on understanding the normal and abnormal endocrine functions involved in the pathogenesis of PCOS. Proper diagnosis and management of the patient is discussed.

  8. Polycystic ovarian syndrome.

    Science.gov (United States)

    Madnani, Nina; Khan, Kaleem; Chauhan, Phulrenu; Parmar, Girish

    2013-01-01

    Polycystic ovarian syndrome (PCOS) is a "multispeciality" disorder suspected in patients with irregular menses and clinical signs of hyperandrogenism such as acne, seborrhoea, hirsutism, irregular menses, infertility, and alopecia. Recently, PCOS has been associated with the metabolic syndrome. Patients may develop obesity, insulin resistance, acanthosis nigricans, Type 2 diabetes, dyslipidemias, hypertension, non-alcoholic liver disease, and obstructive sleep apnoea. Good clinical examination with hematological and radiological investigations is required for clinical evaluation. Management is a combined effort involving a dermatologist, endocrinologist, gynecologist, and nutritionist. Morbidity in addition includes a low "self image" and poor quality of life. Long term medications and lifestyle changes are essential for a successful outcome. This article focuses on understanding the normal and abnormal endocrine functions involved in the pathogenesis of PCOS. Proper diagnosis and management of the patient is discussed.

  9. [Association between obesity and ovarian cancer].

    Science.gov (United States)

    Valladares, Macarena; Corsini, Gino; Romero, Carmen

    2014-05-01

    Obesity is a risk factor for cancer. Epidemiological evidences associate ovarian cancer with obesity. Epithelial ovarian cancer (EOC) is the most common type of ovarian cancer and accounts for a high rate of mortality. The association between ovarian cancer and obesity could be explained by molecular factors secreted by adipose tissue such as leptin. In EOC, leptin increases cell proliferation and inhibits apoptosis. Additionally, adipose tissue synthesizes endogenous estrogens, which increase cell proliferation of epithelial ovarian cells. Also, obesity associated hyperinsulinism could increase ovarian estrogen secretion.

  10. Management of ovarian cysts in infants.

    Science.gov (United States)

    Xue-Qiang, Yan; Nan-Nan, Zheng; Lei, Yu; Wei, Lu; Hong-Qiang, Bian; Jun, Yang; Xu-Fei, Duan; Xin-Ke, Qin

    2015-12-01

    To discuss the experience of diagnosis and treatment of ovarian cyst in infants. A retrospective review was conducted on 20 infants who suffered from ovarian cyst. There were no dysplasia ovarian was found in children which were preoperatively diagnosed simplex cyst. Within thirteen children preoperatively detected mixed cystic-solid lesion, six cases ovarian cysts disappeared and two cases underwent poor blood supply in the following time. Adverse effects for ovarian cyst in infants can be prevented by agressive surgical intervention. Harmful effects of ovarian cyst can be prevented by positive surgical intervention despite the diagnostic difficulties in children with clinical symptoms of this condition.

  11. Premature ovarian failure

    Directory of Open Access Journals (Sweden)

    Vujović Svetlana

    2012-01-01

    Full Text Available Premature ovarian failure (POF is the occurrence of hypergonadotropic hypoestrogenic amenorrhea in women under the age of forty years. It is idiopathic in 74-90% patients. Known cases can be divided into primary and secondary POF. In primary POF genetic aberrations can involve the X chromosome (monosomy, trisomy, translocations, deletions or autosomes. Genetic mechanisms include reduced gene dosage and non-specific chromosome effects impairing meiosis, decreasing the pool of primordial follicles and increasing atresia due to apoptosis or failure of follicle maturation. Autoimmune ovarian damage is caused by alteration of T-cell subsets and T-cell mediated injury, increase of autoantibody producing B-cells, a low number of effector/cytotoxic lymphocyte, which decreases the number and activity of natural killer cells. Bilateral oophorectomy, chemotherapy, radiotherapy and infections cause the secondary POF. Symptoms of POF include irritability, nervousness, loss of libido, depression, lack of concentration, hot flushes, weight gaining, dry skin, vaginal dryness, frequent infections etc. The diagnosis is confirmed by the level of FSH of over 40 IU/L and estradiol below 50 pmol/L in women aged below 40 years. Biochemical and other hormonal analysis (free thyroxin, TSH, prolactin, testosterone, karyotype (<30 years of age, ultrasound of the breasts and pelvis are advisable. Optimal therapy is combined estrogen progestagen therapy given in a sequential rhythm, after excluding absolute contraindications. Testosterone can be added to adnexectomized women and those with a low libido. Sequential estrogen progestagen replacement therapy is the first line therapy for ovulation induction in those looking for pregnancy and after that oocyte donation will be advised. Appropriate estro-progestagen therapy improves the quality of life and prevents complications such as cardiovascular diseases, osteoporosis, stroke etc.

  12. Tamoxifen and ovarian function.

    Directory of Open Access Journals (Sweden)

    Martine Berliere

    Full Text Available BACKGROUND: Some studies suggest that the clinical parameter "amenorrhea" is insufficient to define the menopausal status of women treated with chemotherapy or tamoxifen. In this study, we investigated and compared the ovarian function defined either by clinical or biological parameters in pre-menopausal breast cancer patients treated with tamoxifen administered as adjuvant therapy. MATERIALS AND METHODS: Between 1999 and 2003, 138 premenopausal patients consecutively treated for early breast cancer were included. Sixty-eight received tamoxifen in monotherapy as the only adjuvant systemic treatment (Group I and 70 were treated with tamoxifen after adjuvant chemotherapy (Group II. All patients had a confirmed premenopausal status based on clinical parameters and hormonal values at study entry. They were followed prospectively every 3 months for 3 years: menses data, physical examination and blood tests (LH, FSH, 17-beta-estradiol. Vaginal ultrasonography was carried out every 6 months. After 3 years, prospective evaluation was completed and monitoring of ovarian function was performed as usual in our institution (1x/year. All data were retrospectively evaluated in 2011. RESULTS: Three patients were excluded from the study in group I and 2 were excluded in group II. Patients were divided into 4 subgroups according to clinical data, i.e. menses patterns. These patterns were assessed by questionnaires. a: Regular menses (>10 cycles/year b: Oligomenorrhea (5 to 9 cycles/year c: Severe oligomenorrhea (1 to 4 cycles/year d: Complete amenorrhea Estrogen levels did not appear to have any impact on disease-free survival rates after 3 or 8 years. FSH values were also documented and analyzed. They exhibited the same profile as estradiol values. CONCLUSIONS: Amenorrhea is an insufficient parameter to define menopausal status in patients receiving tamoxifen. Low estradiol levels must be coupled with other biological parameters to characterize endocrine status

  13. Hormone therapy and ovarian cancer

    DEFF Research Database (Denmark)

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

    2009-01-01

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

  14. 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

    . RESULTS: Data are available for 24 women (placebo, n=12; low-dose, n=8; high-dose n=4). A6 therapy was associated with a statistically significant delay in time to clinical progression (log-rank p-value 0.01) with a median of 100 days (95% CI: 64,168) for women who received A6 compared with 49 days (95......% CI: 29,67) for women who received placebo. The treatments appeared to be well tolerated. Treatment was not associated with CA125 response (p=0.44). On-treatment values for plasma urokinase plasminogen activator receptor were statistically significantly lower in the A6 groups compared with placebo (p......=0.02). CONCLUSIONS: A6 therapy increases time to clinical disease progression and appears to be well tolerated in this patient population....

  15. 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.

  16. The advanced glycation end-product Nϵ -carboxymethyllysine promotes progression of pancreatic cancer: implications for diabetes-associated risk and its prevention.

    Science.gov (United States)

    Menini, Stefano; Iacobini, Carla; de Latouliere, Luisa; Manni, Isabella; Ionta, Vittoria; Blasetti Fantauzzi, Claudia; Pesce, Carlo; Cappello, Paola; Novelli, Francesco; Piaggio, Giulia; Pugliese, Giuseppe

    2018-03-13

    Diabetes is an established risk factor for pancreatic cancer (PaC), together with obesity, a Western diet, and tobacco smoking. The common mechanistic link might be the accumulation of advanced glycation end-products (AGEs), which characterizes all of the above disease conditions and unhealthy habits. Surprisingly, however, the role of AGEs in PaC has not been examined yet, despite the evidence of a tumour-promoting role of receptor for advanced glycation end-products (RAGE), the receptor for AGEs. Here, we tested the hypothesis that AGEs promote PaC through RAGE activation. To this end, we investigated the effects of the AGE N ϵ -carboxymethyllysine (CML) in human pancreatic ductal adenocarcinoma (PDA) cell lines and in a mouse model of Kras-driven PaC interbred with a bioluminescent model of proliferation. Tumour growth was monitored in vivo by bioluminescence imaging and confirmed by histology. CML promoted PDA cell growth and RAGE expression, in a concentration-dependent and time-dependent manner, and activated downstream tumourigenic signalling pathways. These effects were counteracted by RAGE antagonist peptide (RAP). Exogenous AGE administration to PaC-prone mice induced RAGE upregulation in pancreatic intraepithelial neoplasias (PanINs) and markedly accelerated progression to invasive PaC. At 11 weeks of age (6 weeks of CML treatment), PaC was observed in eight of 11 (72.7%) CML-treated versus one of 11 (9.1%) vehicle-treated [control (Ctr)] mice. RAP delayed PanIN development in Ctr mice but failed to prevent PaC promotion in CML-treated mice, probably because of competition with soluble RAGE for binding to AGEs and/or compensatory upregulation of the RAGE homologue CD166/ activated leukocyte cell adhesion molecule, which also favoured tumour spread. These findings indicate that AGEs modulate the development and progression of PaC through receptor-mediated mechanisms, and might be responsible for the additional risk conferred by diabetes and other

  17. Apparent diffusion coefficient and vascular signal fraction measurements with magnetic resonance imaging: feasibility in metastatic ovarian cancer at 3 Tesla. Technical development

    International Nuclear Information System (INIS)

    Sala, Evis; Priest, Andrew N.; Kataoka, Masako; Graves, Martin J.; Joubert, Ilse; Lomas, David J.; McLean, Mary A.; Griffiths, John R.; Crawford, Robin A.F.; Jimenez-Linan, Mercedes; Earl, Helena M.; Brenton, James D.

    2010-01-01

    This prospective study aims to evaluate the feasibility of DWI at 3 Tesla in patients with advanced ovarian cancer and investigate the differences in vascular signal fraction (VSF) and apparent diffusion coefficient (ADC) values between primary ovarian mass and metastatic disease. Twenty patients with suspected advanced ovarian carcinoma were enrolled in the study. High-resolution T2W FRFSE images were used to confirm the position of three marker lesions: primary ovarian mass, omental cake and peritoneal deposit. Multislice DWI was acquired in a single breath-hold using multiple b-values. The three marker lesions were outlined by an experienced radiologist on ADC and VSF maps. Ovarian lesions showed the highest ADC values. The mean ADC value for peritoneal deposits was significantly lower than for both ovarian lesions (p = 0.03) and omental cake (p = 0.03). The VSF for omental cake was significantly higher than for ovarian lesions (p = 0.01) and peritoneal deposits (p = 0.04). There was a significant positive correlation between ADC and VSF for peritoneal deposits (p = 0.04). DWI in advanced ovarian cancer is feasible at 3 T. There are significant differences in baseline ADC and VSF values between ovarian cancer, omental cake and peritoneal deposits that may explain the mixed treatment response that occurs at different disease sites. (orig.)

  18. The Thrombospondin-1 Mimetic ABT-510 Increases the Uptake and Effectiveness of Cisplatin and Paclitaxel in a Mouse Model of Epithelial Ovarian Cancer