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Sample records for determines ovarian response

  1. Single nucleotide polymorphisms in the anti-Müllerian hormone signalling pathway do not determine high or low response to ovarian stimulation.

    PubMed

    Hanevik, Hans Ivar; Hilmarsen, Hilde Tveitan; Skjelbred, Camilla Furu; Tanbo, Tom; Kahn, Jarl A

    2010-11-01

    There is substantial variability in ovarian response to exogenous gonadotrophins in women undergoing ovarian stimulation for IVF. Genetic variation in signalling pathways of the ovary could influence ovarian stimulation outcome. Studies have shown a correlation between the serum concentration of anti-Müllerian hormone (AMH) and ovarian stimulation outcome. This paper present a retrospective case-controlled genetic association study designed to test the association between single nucleotide polymorphisms (SNP) in the AMH signalling pathway and two clinically important outcomes of ovarian stimulation: low and high response. Blood samples from 53 high responders, 38 low responders and 100 controls were analysed for eight SNP of interest. Odds ratios and 95% confidence intervals were estimated by a binary logistic regression model adjusting for age and body mass index. As far as is known, this is the first report on the influence of these SNP, present in approximately 19% of women, on ovarian stimulation outcome. No statistically significant association was found between any of the SNP studied and high or low response to ovarian stimulation. It seems unnecessary to detect these SNP when applying the serum concentration of AMH as a predictor of ovarian response to stimulation. Many infertile couples are treated by IVF. Part of this treatment is to pharmacologically stimulate the ovaries to develop many oocytes simultaneously. This process is called ovarian stimulation. Some women respond either too little (low responders) or too much (high responders) to ovarian stimulation. Both these situations are unfavourable to the woman. This study evaluates whether these chances of having one of these two outcomes of ovarian stimulationare influenced by variation in the gene for anti-Müllerian hormone (AMH) or its receptor. This is done by taking blood samples from three groups of patients: low responders, high responders and controls with a normal response. These blood samples

  2. Immune response evaluation through determination of type 1, type 2, and type 17 patterns in patients with epithelial ovarian cancer.

    PubMed

    Cândido, Eduardo Batista; Silva, Luciana Maria; Carvalho, Andréa Teixeira; Lamaita, Rívia Mara; Filho, Roberto Mundim Porto; Cota, Bianca Della Croce Vieira; da Silva-Filho, Agnaldo Lopes

    2013-07-01

    Innate and adaptive immune cells secrete different cytokines, which participate through distinct mechanisms in cell-mediated immunity and humoral immune responses. The aim of this study was to evaluate the immune response through analysis of type 1 (Th1), Th2, and Th17 cells in patients with epithelial ovarian cancer (EOC). Our study included 44 patients with EOC (study group) and 32 gynecological patients with no ovarian disease (control group). Fragments of ovarian tissue and blood samples were collected in both groups and aliquots of intracystic fluid and peritoneal fluid were recovered from the EOC patient group. Interleukin (IL)-2/IL-4/IL-6/IL-10/IL-17/tumor necrosis factor (TNF)-α/interferon (IFN)-γ levels were measured by cytometric bead array. Statistical analysis included chi-squared, Student t, Mann-Whitney, Kruskal-Wallis tests, and Cox regression model. Patients with EOC were associated with higher levels of TNF-α/IL-4/IL-6/IL-10 compared to the control group. Both IL-10 and TNF-α concentrations were higher in patients with stage III/IV EOC and also associated with higher levels of cancer antigen 125. Higher Th1-mediated immune response was observed when the cytoreduction was considered optimal. However, patients with EOC with unsatisfactory cytoreductive surgery and undifferentiated tumors were associated with higher concentrations of Th2 cytokines in the 4 sites studied. Higher IL-6/IL-10 and lower IFN-γ concentrations were also associated with a lower overall survival rate in patients with EOC. The EOC group presented a predominantly Th2 response and an immunosuppressant standard and had association between IL-6/IL-10/IFN-γ and prognosis.

  3. Drug resistance features and S-phase fraction as possible determinants for drug response in a panel of human ovarian cancer xenografts

    PubMed Central

    Kolfschoten, G M; Hulscher, T M; Pinedo, H M; Boven, E

    2000-01-01

    Multidrug resistance (MDR) and more specifically the expression of P-glycoprotein (Pgp) have been studied extensively in vitro. Unfortunately, it appears that the predictive value of MDR recognized in vitro is mostly an incorrect measure to determine the responsiveness of a particular tumour in the clinic. This misunderstood or overvalued role of MDR might explain the failure of strategies to reverse Pgp function by the use of modulators in solid tumours. To obtain more insight in in vivo drug resistance we investigated a panel of 15 human ovarian cancer xenografts consisting of the most common histological subtypes known in ovarian cancer patients. The response rate to cisplatin, cyclophosphamide and doxorubicin in the xenografts resembled the results of phase II trials with these agents in ovarian cancer patients. This resemblance justifies drug resistance studies in this experimental in vivo human tumour system. We determined the expression levels of MDR 1, MRP 1, LRP and topoisomerase IIα mRNA by the RNase protection assay and the presence of MRP1 and LRP proteins by immunohistochemistry. The S-phase fraction was investigated as a separate parameter by flow cytometry. In none of the 15 ovarian cancer xenografts was MDR 1 expression detectable. The expression levels of MRP 1 and LRP were low to moderate and resembled the presence of the MRP1 and LRP proteins. There was a weak, inverse relationship between the expression levels of LRP and sensitivity to cisplatin and cyclophosphamide (r = –0.44 and –0.45), but not to doxorubicin. The levels of topoisomerase IIα varied among the xenografts (0.73–2.66) and failed to correlate with doxorubicin resistance (r = 0.14). The S-phase fraction, however, showed a relation with the sensitivity to cisplatin (r = 0.66). Among the determinants studied in ovarian cancer in vivo, LRP mRNA and the S-phase fraction were the best predictive factors for drug response and most specifically for the activity of cisplatin.

  4. Reference values in ovarian response to controlled ovarian stimulation throughout the reproductive period.

    PubMed

    La Marca, Antonio; Grisendi, Valentina; Spada, Elena; Argento, Cindy; Milani, Silvano; Plebani, Maddalena; Seracchioli, Renato; Volpe, Annibale

    2014-01-01

    Abstract The age-related decline in ovarian response to gonadotropins has been well known since the beginning of ovarian stimulation in IVF cycles and has been considered secondary to the age-related decline in ovarian reserve. The objective of this study was to establish reference values and to construct nomograms of ovarian response for any specific age to gonadotropins in IVF/ICSI cycles. We analyzed our database containing information on IVF cycles. According to inclusion and exclusion criteria, a total of 703 patients were selected. Among inclusion criteria, there were regular menstrual cycle, treatment with a long GnRH agonist protocol and starting follicle-stimulating hormone (FSH) dose of at least 200 IU per day. To estimate the reference values of ovarian response, the CG-LMS method was used. A linear decline in the parameters of ovarian response with age was observed: the median number of oocytes decreases approximately by one every three years, and the median number of follicles >16 mm by one every eight years. The number of oocytes and growing follicles corresponding to the 5th, 25th, 50th, 75th and 95th centiles has been calculated. This study confirmed the well known negative relationship between ovarian response to FSH and female ageing and permitted the construction of nomograms of ovarian response.

  5. Inherited Determinants of Ovarian Cancer Survival

    PubMed Central

    Goode, Ellen L.; Maurer, Matthew J.; Sellers, Thomas A.; Phelan, Catherine M.; Kalli, Kimberly R.; Fridley, Brooke L.; Vierkant, Robert A.; Armasu, Sebastian M.; White, Kristin L.; Keeney, Gary L.; Cliby, William A.; Rider, David N.; Kelemen, Linda E.; Jones, Monica B.; Peethambaram, Prema P.; Lancaster, Johnathan M.; Olson, Janet E.; Schildkraut, Joellen M.; Cunningham, Julie M.; Hartmann, Lynn C.

    2010-01-01

    Purpose Due to variation of outcome among cases, we sought to examine whether overall survival in ovarian cancer was associated with common inherited variants in 227 candidate genes from ovarian cancer-related pathways including angiogenesis, inflammation, detoxification, glycosylation, one-carbon transfer, apoptosis, cell cycle regulation, and cellular senescence. Experimental Design Blood samples were obtained from 325 women with invasive epithelial ovarian cancer diagnosed at the Mayo Clinic from 1999 to 2006. During a median follow-up of 3.8 years (range, 0.1 – 8.6 years), 157 deaths were observed. Germline DNA was analyzed at 1,416 single nucleotide polymorphisms (SNPs). For all patients, and for 203 with serous subtype, we assessed the overall significance of each gene and pathway, and estimated risk of death via hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for known prognostic factors. Results Variation within angiogenesis was most strongly associated with survival time overall (p=0.03) and among patients with serous cancer (p=0.05), particularly for EIF2B5 rs4912474 (all patients HR 0.69, 95% CI 0.54-0.89, p=0.004), VEGFC rs17697305 (serous subtype HR 2.29, 95% CI 1.34-3.92, p=0.003), and four SNPs in VHL. Variation within the inflammation pathway was borderline significant (all patients, p=0.09), and SNPs in CCR3, IL1B, IL18, CCL2, and ALOX5 which correlated with survival time are worthy of follow-up. Conclusion An extensive multiple-pathway assessment found evidence that inherited differences may play a role in outcome of ovarian cancer patients, particularly in genes within the angiogenesis and inflammation pathways. Our work supports efforts to target such mediators for therapeutic gain. PMID:20103664

  6. The meaning of anti-Müllerian hormone levels in patients at a high risk of poor ovarian response

    PubMed Central

    Park, Hyun Jong; Lee, Geun Ho; Gong, Du Sik; Yoon, Tae Ki

    2016-01-01

    Measurements of ovarian reserve play an important role in predicting the clinical results of assisted reproductive technology (ART). The ideal markers of ovarian reserve for clinical applications should have high specificity in order to determine genuine poor responders. Basal follicle-stimulating hormone levels, antral follicle count, and serum anti-Müllerian hormone (AMH) levels have been suggested as ovarian reserve tests that may fulfill this requirement, with serum AMH levels being the most promising parameter. Serum AMH levels have been suggested to be a predictor of clinical pregnancy in ART for older women, who are at a high risk for decreased ovarian response. We reviewed the prognostic significance of ovarian reserve tests for patients undergoing ART treatment, with a particular focus on the significance of serum AMH levels in patients at a high risk of poor ovarian response. PMID:27689035

  7. OVARIAN RESERVE TESTS AND THEIR UTILITY IN PREDICTING RESPONSE TO CONTROLLED OVARIAN STIMULATION IN RHESUS MONKEYS

    PubMed Central

    Wu, Julie M.; Takahashi, Diana L; Ingram, Donald K.; Mattison, Julie A.; Roth, George; Ottinger, Mary Ann; Zelinski, Mary B.

    2010-01-01

    Controlled ovarian stimulation (COS) is an alternative to natural breeding in nonhuman primates; however, these protocols are costly with no guarantee of success. Toward the objective of predicting COS outcome in rhesus monkeys, the current study evaluated three clinically used ovarian reserve tests (ORTs): day 3 (d3) follicle-stimulating hormone (FSH) with d3 inhibin B (INHB), the clomiphene citrate challenge test (CCCT), and the exogenous FSH Ovarian Reserve Test (EFORT). A COS was also performed and response was classified as either successful (COS+) or unsuccessful (COS−) and retrospectively compared to ORT predictions. FSH and INHB were assessed for best hormonal index in conjunction with the aforementioned tests. INHB was consistently more accurate than FSH in all ORTs used. Overall, a modified version of the CCCT using INHB values yielded the best percentage of correct predictions. This is the first report of ORT evaluation in rhesus monkeys and may provide a useful diagnostic test prior to costly follicle stimulations, as well as predicting the onset of menopause. PMID:20336797

  8. YY1 modulates taxane response in epithelial ovarian cancer

    SciTech Connect

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

    2008-10-10

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

  9. Prognostic models for high and low ovarian responses in controlled ovarian stimulation using a GnRH antagonist protocol

    PubMed Central

    Broekmans, Frank J.; Verweij, Pierre J.M.; Eijkemans, Marinus J.C.; Mannaerts, Bernadette M.J.L.; Witjes, Han

    2014-01-01

    STUDY QUESTION Can predictors of low and high ovarian responses be identified in patients undergoing controlled ovarian stimulation (COS) in a GnRH antagonist protocol? SUMMARY ANSWER Common prognostic factors for high and low ovarian responses were female age, antral follicle count (AFC) and basal serum FSH and LH. WHAT IS KNOWN ALREADY Predictors of ovarian response have been identified in GnRH agonist protocols. With the introduction of GnRH antagonists to prevent premature LH rises during COS, and the gradual shift in use of long GnRH agonist to short GnRH antagonist protocols, there is a need for data on the predictability of ovarian response in GnRH antagonist cycles. STUDY DESIGN, SIZE, DURATION A retrospective analysis of data from the Engage trial and validation with the Xpect trial. Prognostic models were constructed for high (>18 oocytes retrieved) and low (<6 oocytes retrieved) ovarian response. Model building was based on the recombinant FSH (rFSH) arm (n = 747) of the Engage trial. Multivariable logistic regression models were constructed in a stepwise fashion (P < 0.15 for entry). Validation based on calibration was performed in patients with equivalent treatment (n = 199) in the Xpect trial. PARTICIPANTS/MATERIALS, SETTING, METHODS Infertile women with an indication for COS prior to IVF. The Engage and Xpect trials included patients of similar ethnic origins from North America and Europe who had regular menstrual cycles. The main causes of infertility were male factor, tubal factor and endometriosis. MAIN RESULTS AND THE ROLE OF CHANCE In the Engage trial, 18.3% of patients had a high and 12.7% had a low ovarian response. Age, AFC, serum FSH and serum LH at stimulation Day 1 were prognostic for both high and low ovarian responses. Higher AFC and LH were associated with an increased chance of high ovarian response. Older age and higher FSH correlated with an increased chance of low ovarian response. Region (North America/Europe) and BMI were

  10. Deciphering the Adaptive Immune Response to Ovarian Cancer

    DTIC Science & Technology

    2014-10-01

    Weinstein JN, Collisson EA, Mills GB, Shaw KR, Ozenberger BA, Ellrott K, Shmulevich I, Sander C, Stuart JM. The Cancer Genome Atlas Pan-Cancer analysis...Holt, Ph.D., John Webb Ph.D., Peter Watson, M.D. Title of Project: Deciphering the Adaptive Immune Response to Ovarian Cancer INTRODUCTION...Cherniack AD, Akbani R, Liu Y, Shen H, Robertson AG, Pashtan I, Shen R, Benz CC, Yau C, Laird PW, Ding L, Zhang W, Mills GB, Kucherlapati R, Mardis ER

  11. Identifying Determinants of PARP Inhibitor Sensitivity in Ovarian Cancer

    DTIC Science & Technology

    2015-10-01

    NOTES 14. ABSTRACT 15. SUBJECT TERMS Ovarian cancer, BRCA1, RAD51, PARP inhibitors, platinum, biomarkers, drug resistance 16. SECURITY CLASSIFICATION...well as mutant BRCA1 protein stabilization in ovarian carcinomas. The expression of mutant BRCA1 or novel proteins identified to be important for drug ...BRCA1 or novel proteins identified to be important for drug resistance will be assessed for their ability to be used as biomarkers of PARP inhibitor

  12. Small cell ovarian carcinoma: genomic stability and responsiveness to therapeutics

    PubMed Central

    2013-01-01

    Background The biology of small cell ovarian carcinoma of the hypercalcemic type (SCCOHT), which is a rare and aggressive form of ovarian cancer, is poorly understood. Tumourigenicity, in vitro growth characteristics, genetic and genomic anomalies, and sensitivity to standard and novel chemotherapeutic treatments were investigated in the unique SCCOHT cell line, BIN-67, to provide further insight in the biology of this rare type of ovarian cancer. Method The tumourigenic potential of BIN-67 cells was determined and the tumours formed in a xenograft model was compared to human SCCOHT. DNA sequencing, spectral karyotyping and high density SNP array analysis was performed. The sensitivity of the BIN-67 cells to standard chemotherapeutic agents and to vesicular stomatitis virus (VSV) and the JX-594 vaccinia virus was tested. Results BIN-67 cells were capable of forming spheroids in hanging drop cultures. When xenografted into immunodeficient mice, BIN-67 cells developed into tumours that reflected the hypercalcemia and histology of human SCCOHT, notably intense expression of WT-1 and vimentin, and lack of expression of inhibin. Somatic mutations in TP53 and the most common activating mutations in KRAS and BRAF were not found in BIN-67 cells by DNA sequencing. Spectral karyotyping revealed a largely normal diploid karyotype (in greater than 95% of cells) with a visibly shorter chromosome 20 contig. High density SNP array analysis also revealed few genomic anomalies in BIN-67 cells, which included loss of heterozygosity of an estimated 16.7 Mb interval on chromosome 20. SNP array analyses of four SCCOHT samples also indicated a low frequency of genomic anomalies in the majority of cases. Although resistant to platinum chemotherapeutic drugs, BIN-67 cell viability in vitro was reduced by >75% after infection with oncolytic viruses. Conclusions These results show that SCCOHT differs from high-grade serous carcinomas by exhibiting few chromosomal anomalies and lacking TP53

  13. Ovarian response prediction in controlled ovarian stimulation for IVF using anti-Müllerian hormone in Chinese women

    PubMed Central

    Zheng, Haiyan; Chen, Shiping; Du, Hongzi; Ling, Jiawei; Wu, Yixuan; Liu, Haiying; Liu, Jianqiao

    2017-01-01

    Abstract The predictive value of anti-Müllerian hormone (AMH) in Chinese women undergoing in vitro fertilization (IVF) treatment is data deficient. To determine the attributes of AMH in IVF, oocyte yield, cycle cancellation, and pregnancy outcomes were analyzed. All patients initiating their first IVF cycle with gonadotropin-releasing hormone agonist treatment in our center from October 2013 through December 2014 were included, except patients diagnosed with polycystic ovarian syndrome. Serum samples collected prior to IVF treatment were used to determine serum AMH levels. A total of 4017 continuous cycles were analyzed. The AMH level was positively correlated with the number of oocytes retrieved. Overall, AMH was significantly correlated with risk of cycle cancellation, poor ovarian response (POR, 3, or fewer oocytes retrieved) and high response (>15 oocytes), with an area under the curve (AUC) of 0.83, 0.89, and 0.82 respectively. An AMH cutoff of 0.6 ng/mL had a sensitivity of 54.0% and a specificity of 90.0% for the prediction of cycle cancellation, and cutoff of 0.8 ng/mL with a sensitivity of 55.0% and a specificity of 94.0% for the prediction of POR. Compared with AMH >2.0 ng/mL, patients with AMH < 0.6 ng/mL had a 53.6-fold increased risk of cancellation (P < 0.001), and AMH <0.80 ng/mL were 17.5 times more likely to experience POR (P < 0.001). However, AMH was less predictive of pregnancy and live birth, with AUCs of 0.55 and 0.53, respectively. Clinical pregnancy rate, ongoing pregnancy rate, and live birth rate per retrieval according to the AMH level (≤0.40, 0.41–0.60, 0.61–0.80, 0.81–1.00, 1.01–1.50, 1.51–2.00, and >2.00 ng/mL) showed no significant differences. Even with AMH≤0.4 ng/mL, 50.0% of all the patients achieved pregnancy and 34.8% of patients achieved live birth after transfer. Our results suggested that AMH is a fairly robust metric for the prediction of cycle cancellation and oocyte yield for Chinese women, but it

  14. Clinical response in patients with ovarian cancer treated with metronomic chemotherapy

    PubMed Central

    Perroud, Herman Andrés; Scharovsky, O Graciela; Rozados, Viviana Rosa; Alasino, Carlos María

    2017-01-01

    Ovarian cancer (OC) is the leading cause of death from gynaecological cancer. It is extremely hard to diagnose in the early stages and around 70% of patients present with advanced disease. Metronomic chemotherapy (MCT) is described as the chronic administration of, generally low, equally spaced, doses of chemotherapeutic drugs with therapeutic efficacy and low toxicity. This is an effective and low-cost way to treat several types of tumours, including ovarian cancer. Here, we present six cases of advanced ovarian cancer treated with MCT with low doses of cyclophosphamide, which showed clinical response and stable disease. PMID:28275392

  15. Proliferation of rhesus ovarian surface epithelial cells in culture: Lack of mitogenic response to steroid or gonadotropic hormones

    SciTech Connect

    Wright, Jay W.; Toth-Fejel, Suellen; Stouffer, Richard L.; Rodland, Karin D.

    2002-06-30

    Ovarian cancer is the most lethal gynecological cancer and approximately 90% of ovarian cancers derive from the ovarian surface epithelium (OSE), yet the biology of the OSE is poorly understood. Factors associated with increased risk of non-hereditary ovarian cancer include the formation of inclusion cysts, effects of reproductive hormones cytokeratin, vimentin, N-cadherin, E-cadherin, estrogen receptor-a, and progesterone receptor. We show that these cells activate MAP Kinase and proliferate in response to extracellular calcium, as do human and rat OSE. In contrast, the gonadotropic hormones FSH (4-400 IU/L), LH (8.5-850 IU/l), and hCG (10-1000 IU/l) fail to stimulate proliferation. We find that concentrations of progesterone and estrogen normally present in follicles just prior to ovulation ( ~1000 ng/ml) significantly decrease the number of mitotically active RhOSE cells as determined by PCNA labelling, total cell count, and 3H-thymidine uptake, while lower steroid concentrations have no effect.

  16. Ovarian response markers lead to appropriate and effective use of corifollitropin alpha in assisted reproduction.

    PubMed

    La Marca, Antonio; D'Ippolito, Giovanni

    2014-02-01

    Corifollitropin alpha is a highly effective gonadotrophin, which maintains multifollicular growth for a week. The advantages of its administration include ease of use of the drug, making the treatment more patient friendly, resulting in a lower level of distress for the patient. At the same time, the pregnancy rate resulting from its use in IVF/intracytoplasmic sperm injection cycles is similar to that found when daily recombinant FSH is administered. The ovarian response to corifollitropin alpha is dependent on clinically established predictors such as baseline FSH, antral follicle count (AFC) and age. There is a general trend towards a higher ovarian response with an increasing AFC and the number of oocytes per attempt decreased with increasing baseline FSH and age. Even if the risk of ovarian hyperstimulation syndrome following corifollitropin alpha is very similar to the rate reported in literature for young women undergoing IVF, the risk of overstimulation may be reduced by avoiding maximal ovarian stimulation in women anticipated to be hyperresponders. High basal anti-Müllerian hormone and/or AFC can identify women with enhanced functional ovarian reserve at risk of overstimulation, and the risk is even higher if maximally stimulated with corifollitropin alpha or high dose of daily recombinant FSH. Corifollitropin alpha is a highly effective gonadotrophin which maintains multifollicular growth for a week. The ovarian response to corifollitropin was demonstrated to be dependent on clinically established predictors such as baseline FSH, antral follicle count (AFC) and age. There was a general trend toward a higher ovarian response with an increasing AFC and the mean number of oocytes per attempt decreased with increasing baseline FSH and age. Even if the risk of ovarian hyperstimulation syndrome (OHSS) following corifollitropin alpha is very similar to the rate of OHSS reported in literature for young women undergoing IVF, the risk of overstimulation may be

  17. Seminal plasma regulates ovarian progesterone production, leukocyte recruitment and follicular cell responses in the pig.

    PubMed

    O'Leary, S; Jasper, M J; Robertson, S A; Armstrong, D T

    2006-07-01

    Seminal plasma (SP) acts to influence the uterine endometrium after mating, activating synthesis of embryotrophic cytokines and inflammatory changes that condition the tract for embryo implantation and establishing pregnancy. The objective of this study was to investigate in pigs whether the ovary might also be responsive to SP exposure. Prepubertal gilts were synchronised with exogenous gonadotrophins and received transcervical treatment with pooled boar SP or PBS; then the ovarian tissue was recovered at 34 h (preovulation) and on days 5 and 9 after treatment. The ovarian response was assessed by measuring ovulation rate, number and size of corpora lutea, ovarian leukocyte populations, progesterone production in vivo, as well as responses of retrieved granulosa cells cultured in vitro. In SP-treated gilts, leukocyte recruitment into the ovarian tissues was increased fourfold at 34 h, with macrophages comprising the most abundant cell lineage. There was no effect of SP on the number of oocytes ovulated; however, the weight of corpora lutea was increased in SP-treated gilts. SP also induced an increase in plasma progesterone content seen from day 5 to at least day 9 after treatment. In addition, granulosa cells and thecal tissue retrieved from preovulatory follicles of SP-treated gilts were more responsive in vitro to growth factor- and gonadotrophin-stimulated cell proliferation and progesterone synthesis. These results suggest that uterine exposure to SP influences immune cell trafficking in the ovary and enhances steroidogenesis in early pregnancy. The effects of SP on ovarian function potentially contribute to reproductive success in the pig.

  18. Follicle-stimulating hormone receptor (FSHR) alternative skipping of exon 2 or 3 affects ovarian response to FSH.

    PubMed

    Karakaya, Cengiz; Guzeloglu-Kayisli, Ozlem; Hobbs, Rebecca J; Gerasimova, Tsilya; Uyar, Asli; Erdem, Mehmet; Oktem, Mesut; Erdem, Ahmet; Gumuslu, Seyhan; Ercan, Deniz; Sakkas, Denny; Comizzoli, Pierre; Seli, Emre; Lalioti, Maria D

    2014-07-01

    Genes critical for fertility are highly conserved in mammals. Interspecies DNA sequence variation, resulting in amino acid substitutions and post-transcriptional modifications, including alternative splicing, are a result of evolution and speciation. The mammalian follicle-stimulating hormone receptor (FSHR) gene encodes distinct species-specific forms by alternative splicing. Skipping of exon 2 of the human FSHR was reported in women of North American origin and correlated with low response to ovarian stimulation with exogenous follicle-stimulating hormone (FSH). To determine whether this variant correlated with low response in women of different genetic backgrounds, we performed a blinded retrospective observational study in a Turkish cohort. Ovarian response was determined as low, intermediate or high according to retrieved oocyte numbers after classifying patients in four age groups (<35, 35-37, 38-40, >40). Cumulus cells collected from 96 women undergoing IVF/ICSI following controlled ovarian hyperstimulation revealed four alternatively spliced FSHR products in seven patients (8%): exon 2 deletion in four patients; exon 3 and exons 2 + 3 deletion in one patient each, and a retention of an intron 1 fragment in one patient. In all others (92%) splicing was intact. Alternative skipping of exons 2, 3 or 2 + 3 were exclusive to low responders and was independent of the use of agonist or antagonist. Interestingly, skipping of exon 3 occurs naturally in the ovaries of domestic cats--a good comparative model for human fertility. We tested the signaling potential of human and cat variants after transfection in HEK293 cells and FSH stimulation. None of the splicing variants initiated cAMP signaling despite high FSH doses, unlike full-length proteins. These data substantiate the occurrence of FSHR exon skipping in a subgroup of low responders and suggest that species-specific regulation of FSHR splicing plays diverse roles in mammalian ovarian function.

  19. [Anti mullerian hormone (AMH)--is it a new reliable marker of the ovarian reserve? Its role in predicting the ovarian response in assisted reproductive technology (ART)].

    PubMed

    Alshiek, Jonia Amer; Lessing, Joseph B; Amit, Ami; Azem, Foad

    2012-07-01

    Anti-Müllerian hormone (AMH) is predominantly known for its important role in the differentiation of the male and female sexual system during the early embryonic period. Recently, many animal and human researches have been studying the role of the AMH in the postnatal ovarian function. In the female, AMH is produced by the granulosa cells of early developing follicles. It plays a major role in the folliculogenesis and seems to be able to inhibit the initiation of the growth of primordial follicles and FSH-induced follicles. As AMH is expressed throughout the folliculogenesis, from the primary follicular stage to the antral stage, the serum levels of AMH may represent both the quantity and the quality of ovarian follicles. Thus, the AMH levels may be useful as a new potential marker of the ovarian reserve. As compared to other ovarian reserve tests, the AMH has unique characteristics which make it a favorable marker. The measurement of AMH levels may be useful in the prediction of poor response and cycle cancellation as well as hyper-response and the ovarian hyperstimulation syndrome in assisted reproductive technology (ART). We assume that the measurement of AMH Levels may play a role in the individualization of treatment strategies among patients who are treated by ART. However, the AMH cannot predict the qualitative ovarian response in ART. In men, the AMH was not found to have satisfactory clinical utility as a single marker of spermatogenesis.

  20. Association between individual ovarian dimensions with ovarian reserve indices

    PubMed Central

    Naeini, Elham Hashemian; Neyestanak, Mohammad Zare; Berjis, Katayon; Shokoohi, Mostafa

    2013-01-01

    Introduction: In some young female candidates of assisted reproductive technology (ART), ovarian response to simulative treatments is less than what is expected. More precise assessment of oocyte quality and quantity through studying ovarian dimensions can be useful for determining the dose of ovarian stimulant drugs and for preventing ART cycles cancellation. The aim of the present study is to determine the association between ovarian dimensions and ovarian reserve (OR) indices and whether ovarian dimensions can predict ovarian reserve. Methods: In this cross-sectional study, 85 infertile women were studied. In early follicular phase, ovarian diameters (including length and width of the ovaries) were measured using transvaginal ultrasonography. Mean ovarian diameters (MOD) were calculated according to average length and width of the ovaries. A serum sample was taken from all patients to measure the level of Follicular Stimulating Hormone (FSH) and oestradiol as OR indices. Results: The results of univariate analysis showed that FSH and oestradiol had a negative significant association with width, length and MOD (P < 0.01). The results of multivariate regression analysis showed that FSH and oestradiol had a negative significant association with width (βFSH = -0.59, P = 0.001 and βOestradiol = -0.019, P = 0.029) and MOD (βFSH = -0.52, P = 0.003 and βOestradiol = -0.021, P = 0.017) and had a borderline negative significant correlation with ovarian length (βFSH = -0.49, P=0.077 and βOestradiol = 0.022, P = 0.08) Conclusions: The results of this study revealed that despite a moderate correlation, ovarian diameters could be an applicable index for predicting OR. Using this method along with other methods may be useful in treatment with ovarian stimulants. PMID:26966426

  1. Small-Molecule RA-9 Inhibits Proteasome-Associated DUBs and Ovarian Cancer in Vitro and in Vivo Via Exacerbating Unfolded Protein Responses

    PubMed Central

    Coughlin, Kathleen; Anchoori, Ravi; Iizuka, Yoshie; Meints, Joyce; MacNeill, Lauren; Vogel, Rachel Isaksson; Orlowski, Robert Z.; Lee, Michael K.; Roden, Richard BS; Bazzaro, Martina

    2014-01-01

    Purpose Ovarian cancer is the deadliest of the gynecological malignancies. Carcinogenic progression is accompanied by up-regulation of ubiquitin-dependent protein degradation machinery as a mechanism to compensate with elevated endogenous proteotoxic stress. Recent studies support the notion that deubiquitinating enzymes (DUBs) are essential factors in proteolytic degradation and that their aberrant activity is linked to cancer progression and chemoresistance. Thus, DUBs are an attractive therapeutic target for ovarian cancer. Experimental Design The potency and selectivity of RA-9 inhibitor for proteasome-associated DUBs was determined in ovarian cancer cell lines and primary cells. The anticancer activity of RA-9 and its mechanism of action was evaluated in multiple cancer cell lines in vitro and in vivo in immunodeficient mice bearing an intra-peritoneal ES-2 xenograft model of human ovarian cancer. Results Here we report the characterization of RA-9 as a small-molecule inhibitor of proteasome-associated DUBs. Treatment with RA-9 selectively induces onset of apoptosis, in ovarian cancer cell lines and primary cultures derived from donors. Loss of cell viability following RA-9 exposure is associated with an Unfolded Protein Response (UPR) as mechanism to compensate for unsustainable levels of proteotoxic stress. In vivo treatment with RA-9 retards tumor growth, increases overall survival and was well tolerated by the host. Conclusions Our preclinical studies support further evaluation of RA-9 as an ovarian cancer therapeutic. PMID:24727327

  2. Morphologic responses of the mouse ovarian surface epithelium to ovulation and steroid hormonal milieu.

    PubMed

    Gotfredson, Garry S; Murdoch, William J

    2007-02-01

    Ovarian cancer of surface epithelial origin is an ovulation- and endocrine-related disease. It appears that a cell transformed by genotoxins generated at follicular rupture is propagated during postovulatory wound repair. A consequent steroid hormonal imbalance favoring the mitogenic estrogens is a prospective predisposing factor in ovarian neoplasia. Protection against epithelial ovarian cancer is conferred by progesterone. The objective of this study was to characterize the acute effects of ovulation and steroid hormonal exposure on morphologic responses of surface epithelial cells of mouse ovaries. Follicular development and ovulation were induced in immature animals with equine and human (=Day 0) choriogonadotropins, respectively. On Day 2 (approximately 36 hrs after ovulation), surface epithelial classifications presented in histologic sections were altered from simple (single-layered) squamous and cuboidal toward stratification; this trend was reversed (i.e., reverted to the control status) on Days 4-8. Shifts in the ovarian epithelium from simple to stratified were accentuated following postovulatory (Days 1-8) treatment with estradiol. Surface epithelia of ovaries obtained after 1 week of progesterone administration were exclusively of a simple phenotype. We conclude that the proliferative/procarcinogenic reaction of the ovarian surface epithelium to ovulation is exacerbated by estrogen and counteracted by progesterone.

  3. In vitro ovarian tumor growth and treatment response dynamics visualized with time-lapse OCT imaging

    PubMed Central

    Evans, Conor L.; Rizvi, Imran; Hasan, Tayyaba; de Boer, Johannes F.

    2010-01-01

    In vitro three-dimensional models for metastatic ovarian cancer have been useful for recapitulating the human disease. These spheroidal tumor cultures, however, can grow in excess of 1 mm in diameter, which are difficult to visualize without suitable imaging technology. Optical coherence tomography (OCT) is an ideal live imaging method for non-perturbatively visualizing these complex systems. OCT enabled detailed observations of the model at both nodular and cellular levels, revealing growth dynamics not previously observed. The development of a time-lapse OCT system, capable of automated, multidimensional acquisition, further provided insights into the growth and chemotherapeutic response of ovarian cancer. PMID:19466138

  4. Basal serum testosterone levels correlate with ovarian reserve and ovarian response in cycling women undergoing in vitro fertilization.

    PubMed

    Xiao, Shan; Li, Yubin; Long, Lingli; Luo, Canqiao; Mai, Qingyun

    2016-01-01

    This study aimed to investigate the association between basal serum testosterone levels and in vitro fertilization (IVF) parameters in cycling women. A retrospective cohort study was performed at a clinical IVF center, and 495 women with regular menstruation were enrolled. Serum testosterone levels were measured before the start of IVF treatment cycle. We found that basal serum testosterone levels were negatively associated with female age and FSH/LH ratios. In contrast, we found a positive correlation between serum testosterone levels and the number of oocytes and available embryos. However, there was no significant association between testosterone levels and pregnancy outcome. Our results suggest that basal serum testosterone levels were significantly related to certain classic indicators of ovarian reserve, such as age and FSH/LH ratios. Increased testosterone levels improved ovarian response in cycling women, but they fail to predict pregnancy and miscarriage rate.

  5. Effects of high progesterone on outcomes of in vitro fertilization-embryo transfer in patients with different ovarian responses.

    PubMed

    Li, Peng-fen; Zhu, Hong; Tan, Li; Zhao, Dong-mei; Ma, Li-ying; Xiang, Yun-gai; Zhang, Dan; Dou, Qian; Lu, Na

    2015-06-01

    The data of 3,841 cycles undergoing in vitro fertilization-embryo transfer (IVF-ET) in our reproductive Center between January 2003 and December 2013 were retrospectively analyzed. According to the number of oocytes retrieved, this study was divided into the high ovarian response group (oocyte retrieval≥20, 842 cycles), the moderate ovarian response group (5ovarian response group (oocyte retrieval≤5, 991 cycles). The treatment outcomes were compared between the patients with an increased progesterone (P) level and the patients where the P level did not increase. With increase in ovarian response, the cut-off values of serum P on the day of human chorionic gonadotrophin (hCG) rose, and respectively were 2.5 ng/ml in the high ovarian response group, 2.25 ng/ml in the moderate ovarian response group, and 1.5 ng/ml in the low ovarian response group. In each group, the clinical pregnancy rate and embryo implantation rate were lower in the patients with an increased P level compared to those where the P level did not increase (all p<0.05). However, there were no significant difference in the fertilization rate, cleavage rate, and high-quality embryo rate (all p>0.05). The increased level of P on the day of hCG may affect the treatment outcomes of IVF-ET. The cut-off values of serum P seem to be associated with ovarian response. Increased ovarian response causes the cut-off values of serum P to rise.

  6. Clinical value of serum anti-mullerian hormone and inhibin B in prediction of ovarian response in patients with polycystic ovary syndrome.

    PubMed

    Zhang, Fan; Liu, Xiao-Ling; Rong, Nan; Huang, Xiao-Wen

    2017-02-01

    The present study aimed to investigate the clinical value of serum anti-mullerian hormone (AMH) and inhibin B (INHB) in predicting the ovarian response of patients with polycystic ovary syndrome (PCOS). A total of 120 PCOS patients were enrolled and divided into three groups in terms of the ovarian response: a low-response group (n=36), a normal-response group (n=44), and a high-response group (n=40). The serum AMH and INHB levels were measured by enzyme-linked immunosorbent assay (ELISA). The follicle stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) levels were determined by chemiluminescence microparticle immunoassay. The correlation of the serum AMH and INHB levels with other indicators was analyzed. A receiver operating characteristic (ROC) curve was established to analyze the prediction of ovarian response by AMH and INHB. The results showed that there were significant differences in age, body mass index (BMI), FSH, total gonadotropin-releasing hormone (GnRH), LH, E2, and antral follicle counts (AFCs) between the groups (P<0.05). The serum AMH and INHB levels were increased significantly with the ovarian response of PCOS patients increasing (P<0.05). The serum AMH and INHB levels were negatively correlated with the age, BMI, FSH level, Gn, and E2 levels (P<0.05). They were positively correlated with the LH levels and AFCs (P<0.05). ROC curve analysis of serum AMH and INHB in prediction of a low ovarian response showed that the area under the ROC curve (AUC) value of the serum AMH level was 0.817, with a cut-off value of 1.29 ng/mL. The sensitivity and specificity were 71.2% and 79.6%, respectively. The AUC value of serum INHB was 0.674, with a cut-off value of 38.65 ng/mL, and the sensitivity and specificity were 50.7% and 74.5%, respectively. ROC curve analysis showed when the serum AMH and INHB levels were used to predict a high ovarian response, the AUC value of the serum AMH level was 0.742, with a cut-off value of 2.84 ng/mL, and

  7. Determine the Role of Canonical Wnt Signaling in Ovarian Tumorigenesis

    DTIC Science & Technology

    2012-10-01

    Goldstein M, Sellers WR, Yaron Y , et al. Multiple genes in human 20q13 chromosomal region are involved in an advanced prostate cancer xenograft...Months 1-12) Specifically, we will determine whether inhibition of canonical Wnt signaling induces the expression of markers of senescence in human...cells treated with FJ9 demonstrated features of senescence such as a large flat cell morphology (Figure 1B). However, examination of markers of canonical

  8. ALDH enzymatic activity and CD133 positivity and response to chemotherapy in ovarian cancer patients.

    PubMed

    Ricci, Francesca; Bernasconi, Sergio; Porcu, Luca; Erba, Eugenio; Panini, Nicolò; Fruscio, Robert; Sina, Federica; Torri, Valter; Broggini, Massimo; Damia, Giovanna

    2013-01-01

    The prognostic/predictive role of both CD133 and Aldehyde dehydrogenase (ALDH) expression in human ovarian cancer remains elusive. This is an observational study that investigated the expression of CD133 and of ALDH enzymatic activity in fresh ovarian cancer samples and their association with different clinic-pathological patient' characteristics and explored their possible predictive/prognostic role. We analyzed the expression of CD133 and ALDH enzymatic activity in 108 human ovarian cancer samples. We found that among the total patients analyzed, 13% of them was completely negative for ALDH activity and 26% was negative for CD133 staining. Both markers were variably expressed within the samples and when both studied in the same tumor sample, no statistically significant correlation between ALDH enzymatic activity and CD133 expression was found. No statistical significant correlation was found also between the percentage values of positive ALDH and CD133 cells and the number of serial passages patient's cultures underwent, suggesting that these markers do not confer by themselves a self-renewal growth advantage to the cultures. Lower levels of CD133 were associated with higher tumor grade. No correlation with response to therapy, progression free survival and overall survival was found. Our data suggest that neither ALDH enzymatic activity nor CD133 expression provide additional predictive/prognostic information in ovarian cancer patients.

  9. High progesterone levels in women with high ovarian response do not affect clinical outcomes: a retrospective cohort study

    PubMed Central

    2014-01-01

    Background The potentially detrimental role of progesterone during the follicular phase has been a matter of controversy for several years; however, few studies have analyzed the effects of combined raised estradiol and progesterone levels on pregnancy outcomes. The aim of the present study was to determine the influence of high progesterone levels on clinical outcomes in the context of high ovarian response. Methods We performed a retrospective cohort study that included 2850 women classified as high responders. The women were subdivided into six groups depending on their progesterone concentration on the day of human chorionic gonadotropin (hCG) administration: <0.5 ng/ml (1.81 ng/ml (>p90). Ovarian response was classified as high when > =20 oocytes were retrieved or when estradiol was > =3000 pg/ml. Clinical outcomes of each subgroup were analyzed. We also examined data from frozen-thawed embryo transfers. Results were analyzed with Student’s t- test to compare continuous variables and chi-squared test to compare proportions. A p-value of < =0.05 was considered statistically significant. Results The progesterone concentration increased with ovarian response, and elevated progesterone did not show a significant clinical impact on implantation rate and pregnancy rates. These data provide evidence that progesterone levels higher than 1.8 ng/ml do not have detrimental effect on oocyte quality or endometrial receptivity. Conclusions These data allow us to conclude that high progesterone levels correlate significantly with high estradiol levels and that in high responder women; progesterone levels do not show a significant clinical impact on results. PMID:25064138

  10. Genetic testing for hereditary breast and ovarian cancer: responsibility and choice.

    PubMed

    d'Agincourt-Canning, Lori

    2006-01-01

    Genetic testing for hereditary breast-ovarian cancer has become an important part of clinical genetics practice. Although considerable work has focused on the psychological impact of this technology, there has been little research into the moral implications of genetic information on hereditary cancer families. In this article, the author examines moral issues related to individuals' decisions to seek or decline testing. In-depth interviews with 53 participants make up the core of the research. Analysis of participants' accounts illustrates how the decision to be tested (or not) interconnects with moral agency and aspects of self (embodied, familial-relational, and civic self). The findings form the foundation for inquiry into conceptualization of moral responsibility, autonomy, and choice. They also provide insight that might assist clinicians to understand more fully the needs and responses of those who seek genetic testing for hereditary breast-ovarian cancer.

  11. Ovarian response prediction in controlled ovarian stimulation for IVF using anti-Müllerian hormone in Chinese women: A retrospective cohort study.

    PubMed

    Zheng, Haiyan; Chen, Shiping; Du, Hongzi; Ling, Jiawei; Wu, Yixuan; Liu, Haiying; Liu, Jianqiao

    2017-03-01

    The predictive value of anti-Müllerian hormone (AMH) in Chinese women undergoing in vitro fertilization (IVF) treatment is data deficient. To determine the attributes of AMH in IVF, oocyte yield, cycle cancellation, and pregnancy outcomes were analyzed. All patients initiating their first IVF cycle with gonadotropin-releasing hormone agonist treatment in our center from October 2013 through December 2014 were included, except patients diagnosed with polycystic ovarian syndrome. Serum samples collected prior to IVF treatment were used to determine serum AMH levels. A total of 4017 continuous cycles were analyzed. The AMH level was positively correlated with the number of oocytes retrieved. Overall, AMH was significantly correlated with risk of cycle cancellation, poor ovarian response (POR, 3, or fewer oocytes retrieved) and high response (>15 oocytes), with an area under the curve (AUC) of 0.83, 0.89, and 0.82 respectively. An AMH cutoff of 0.6 ng/mL had a sensitivity of 54.0% and a specificity of 90.0% for the prediction of cycle cancellation, and cutoff of 0.8 ng/mL with a sensitivity of 55.0% and a specificity of 94.0% for the prediction of POR. Compared with AMH >2.0 ng/mL, patients with AMH < 0.6 ng/mL had a 53.6-fold increased risk of cancellation (P < 0.001), and AMH <0.80 ng/mL were 17.5 times more likely to experience POR (P < 0.001). However, AMH was less predictive of pregnancy and live birth, with AUCs of 0.55 and 0.53, respectively. Clinical pregnancy rate, ongoing pregnancy rate, and live birth rate per retrieval according to the AMH level (≤0.40, 0.41-0.60, 0.61-0.80, 0.81-1.00, 1.01-1.50, 1.51-2.00, and >2.00 ng/mL) showed no significant differences. Even with AMH≤0.4 ng/mL, 50.0% of all the patients achieved pregnancy and 34.8% of patients achieved live birth after transfer. Our results suggested that AMH is a fairly robust metric for the prediction of cycle cancellation and oocyte yield for Chinese women, but it is a relatively

  12. ESHRE consensus on the definition of 'poor response' to ovarian stimulation for in vitro fertilization: the Bologna criteria.

    PubMed

    Ferraretti, A P; La Marca, A; Fauser, B C J M; Tarlatzis, B; Nargund, G; Gianaroli, L

    2011-07-01

    The definition presented here represents the first realistic attempt by the scientific community to standardize the definition of poor ovarian response (POR) in a simple and reproducible manner. POR to ovarian stimulation usually indicates a reduction in follicular response, resulting in a reduced number of retrieved oocytes. It has been recognized that, in order to define the poor response in IVF, at least two of the following three features must be present: (i) advanced maternal age or any other risk factor for POR; (ii) a previous POR; and (iii) an abnormal ovarian reserve test (ORT). Two episodes of POR after maximal stimulation are sufficient to define a patient as poor responder in the absence of advanced maternal age or abnormal ORT. By definition, the term POR refers to the ovarian response, and therefore, one stimulated cycle is considered essential for the diagnosis of POR. However, patients of advanced age with an abnormal ORT may be classified as poor responders since both advanced age and an abnormal ORT may indicate reduced ovarian reserve and act as a surrogate of ovarian stimulation cycle outcome. In this case, the patients should be more properly defined as 'expected poor responder'. If this definition of POR is uniformly adapted as the 'minimal' criteria needed to select patients for future clinical trials, more homogeneous populations will be tested for any new protocols. Finally, by reducing bias caused by spurious POR definitions, it will be possible to compare results and to draw reliable conclusions.

  13. Dehydroepiandrosterone improves the ovarian reserve of women with diminished ovarian reserve and is a potential regulator of the immune response in the ovaries.

    PubMed

    Zhang, Jiali; Qiu, Xuemin; Gui, Yuyan; Xu, Yingping; Li, Dajin; Wang, Ling

    2015-12-01

    Diminished ovarian reserve (DOR) has a high morbidity rate worldwide and has become a primary cause of infertility. DOR is a daunting obstacle in in vitro fertilization (IVF) and leads to poor ovarian response, high cancellation rates, poor IVF outcomes, and low pregnancy rates. Abnormal autoimmune function may also contribute to DOR. Dehydroepiandrosterone (DHEA) is a C19 androgenic steroid. DHEA is secreted mainly by the adrenal gland, and its secretion declines with age. DHEA has a pro-inflammatory immune function that opposes cortisol. The cortisol to DHEA ratio increases with age, which may lead to decreased immune function. DHEA supplementation helps improve this situation. A number of clinical case control studies and several prospective randomized clinical trials have observed a positive effect of DHEA supplementation in women with DOR. However, the underlying mechanism by which DHEA improves ovarian reserve remains unclear. DHEA functions as an immune regulator in many different tissues in mammals and may also play an important role in regulating the immune response in the ovaries. The conversion of DHEA to downstream sex steroids may allow it to regulate the immune response there. DHEA can also enhance the Th1 immune response and regulate the balance of the Th1/Th2 response. DHEA treatment can increase selective T lymphocyte infiltration in mice, resulting in a decline in the CD4+ T lymphocyte population and an upregulation of the CD8+ T lymphocyte population in ovarian tissue, thus regulating the balance of CD4+/CD8+ T cells. This review mainly focuses on how DHEA supplementation affects regulation of the immune response in the ovaries.

  14. SPARC Regulates Transforming Growth Factor Beta Induced (TGFBI) Extracellular Matrix Deposition and Paclitaxel Response in Ovarian Cancer Cells

    PubMed Central

    Andrews, Melissa R.; Brenton, James D.

    2016-01-01

    TGFBI has been shown to sensitize ovarian cancer cells to the cytotoxic effects of paclitaxel via an integrin receptor-mediated mechanism that modulates microtubule stability. Herein, we determine that TGFBI localizes within organized fibrillar structures in mesothelial-derived ECM. We determined that suppression of SPARC expression by shRNA decreased the deposition of TGFBI in mesothelial-derived ECM, without affecting its overall protein expression or secretion. Conversely, overexpression of SPARC increased TGFBI deposition. A SPARC-YFP fusion construct expressed by the Met5a cell line co-localized with TGFBI in the cell-derived ECM. Interestingly, in vitro produced SPARC was capable of precipitating TGFBI from cell lysates dependent on an intact SPARC carboxy-terminus with in vitro binding assays verifying a direct interaction. The last 37 amino acids of SPARC were shown to be required for the TGFBI interaction while expression of a SPARC-YFP construct lacking this region (aa 1–256) did not interact and co-localize with TGFBI in the ECM. Furthermore, ovarian cancer cells have a reduced motility and decreased response to the chemotherapeutic agent paclitaxel when plated on ECM derived from mesothelial cells lacking SPARC compared to control mesothelial-derived ECM. In conclusion, SPARC regulates the fibrillar ECM deposition of TGFBI through a novel interaction, subsequently influencing cancer cell behavior. PMID:27622658

  15. BRCA Mutation Frequency and Patterns of Treatment Response in BRCA Mutation–Positive Women With Ovarian Cancer: A Report From the Australian Ovarian Cancer Study Group

    PubMed Central

    Alsop, Kathryn; Fereday, Sian; Meldrum, Cliff; deFazio, Anna; Emmanuel, Catherine; George, Joshy; Dobrovic, Alexander; Birrer, Michael J.; Webb, Penelope M.; Stewart, Colin; Friedlander, Michael; Fox, Stephen; Bowtell, David; Mitchell, Gillian

    2012-01-01

    Purpose The frequency of BRCA1 and BRCA2 germ-line mutations in women with ovarian cancer is unclear; reports vary from 3% to 27%. The impact of germ-line mutation on response requires further investigation to understand its impact on treatment planning and clinical trial design. Patients and Methods Women with nonmucinous ovarian carcinoma (n = 1,001) enrolled onto a population-based, case-control study were screened for point mutations and large deletions in both genes. Survival outcomes and responses to multiple lines of chemotherapy were assessed. Results Germ-line mutations were found in 14.1% of patients overall, including 16.6% of serous cancer patients (high-grade serous, 22.6%); 44% had no reported family history of breast or ovarian cancer. Patients carrying germ-line mutations had improved rates of progression-free and overall survival. In the relapse setting, patients carrying mutations more frequently responded to both platin- and nonplatin-based regimens than mutation-negative patients, even in patients with early relapse after primary treatment. Mutation-negative patients who responded to multiple cycles of platin-based treatment were more likely to carry somatic BRCA1/2 mutations. Conclusion BRCA mutation status has a major influence on survival in ovarian cancer patients and should be an additional stratification factor in clinical trials. Treatment outcomes in BRCA1/2 carriers challenge conventional definitions of platin resistance, and mutation status may be able to contribute to decision making and systemic therapy selection in the relapse setting. Our data, together with the advent of poly(ADP-ribose) polymerase inhibitor trials, supports the recommendation that germ-line BRCA1/2 testing should be offered to all women diagnosed with nonmucinous, ovarian carcinoma, regardless of family history. PMID:22711857

  16. Seasonal effects on ovarian responsiveness to exogenous gonadotrophins and successful artificial insemination in the snow leopard (Uncia uncia).

    PubMed

    Roth, T L; Armstrong, D L; Barrie, M T; Wildt, D E

    1997-01-01

    Ovaries of the seasonally-breeding snow leopard (Uncia uncia) were examined to determine whether they were responsive to exogenous gonadotrophins throughout the year. The potential of laparoscopic artificial insemination (AI) also was assessed for producing offspring. During the non-breeding, pre-breeding, breeding and post-breeding seasons, females (n = 20) were treated with a standardized, dual-hormone regimen given intramuscularly (600 I.U. of equine chorionic gonadotrophin followed 80-84 h later with 300 I.U. of human chorionic gonadotrophin (hCG)). Laparoscopy was performed 45-50 h after administration of hCG, and all ovarian structures were described. Females with fresh corpora lutea (CL) were inseminated, and anovulatory females were subjected to follicular aspiration to examine oocyte quality. Snow leopards responded to exogenous gonadotrophins throughout the year. Mean number of total ovarian structures (distinct follicles mature in appearance plus CL) did not differ (P > or = 0.05) with season, but the proportion of CL: total ovarian structures was greater (P < 0.01) for the breeding season compared with all other seasons. The proportion of females ovulating was greater (P < 0.05) during the breeding and post-breeding seasons than during the pre-breeding and non-breeding seasons respectively. No Grade-1 quality oocytes were recovered from follicles of anovulatory females. Serum concentrations of oestradiol-17 beta appeared elevated in all females, and neither oestradiol-17 beta concentrations nor progesterone concentrations differed (P > or = 0.05) among seasons. Of 15 females artificially inseminated, the only one that was inseminated in the non-breeding season became pregnant and delivered a single cub. This is the first successful pregnancy resulting from AI in this endangered species.

  17. Differential physiological responses of the German cockroach to social interactions during the ovarian cycle.

    PubMed

    Uzsák, Adrienn; Schal, Coby

    2012-09-01

    In many animal species, social interactions can influence the morphology, physiology and behavior of individuals, including their rate of development and reproduction. Reproduction in cockroaches is regulated by juvenile hormone III (JH), and social interactions have been shown to accelerate female reproduction in the German cockroach, Blattella germanica (L.), by stimulating JH production. However, it is not clear in this or any other insect species whether social facilitation of the reproductive rate occurs throughout the ovarian cycle or only at certain stages. We compared the effects of social interactions during the pre-oviposition period (when JH production is high) and during gestation (when little JH is produced), as well as during the first ovarian cycle (when females are virgin) and the second ovarian cycle (after females had mated). Social interaction with one conspecific female was sufficient to accelerate JH production and oocyte maturation, but this effect was reversed by crowding. Social interactions also accelerated the onset of sexual receptivity in virgin females. However, social interactions failed to shorten gestation, suggesting that social cues stimulate JH production only when the corpora allata (CA) are active and not when CA activity is suppressed by the central nervous system. Females were most responsive to transient social isolation and transient social interactions when 2-3 days old, suggesting that they are particularly sensitive to social interactions when their CA become active. Overall, these results show that all JH-dependent events in the reproductive cycle of B. germanica females are under the strong influence of social interactions.

  18. Polymorphisms in gonadotropin and gonadotropin receptor genes as markers of ovarian reserve and response in in vitro fertilization.

    PubMed

    La Marca, Antonio; Sighinolfi, Giovanna; Argento, Cindy; Grisendi, Valentina; Casarini, Livio; Volpe, Annibale; Simoni, Manuela

    2013-03-15

    Since gonadotropins are the fundamental hormones that control ovarian activity, genetic polymorphisms may alter gonadal responsiveness to glycoproteins; hence they are important regulators of hormone activity at the target level. The establishment of the pool of primordial follicles takes place during fetal life and is mainly under genetic control. Consequently, single nucleotide polymorphisms (SNPs) in gonadotropins and their receptors do not seem to be associated with any significant modification in the endowment of nongrowing follicles in the ovary. Indeed, the age at menopause, a biological characteristic strongly related to ovarian reserve, as well as markers of functional ovarian reserve such as anti-Müllerian hormone and antral follicle count, are not different in women with different genetic variants. Conversely, some polymorphisms in FSH receptor (FSHR) seem to be associated with modifications in ovarian activity. In particular, studies suggest that the Ser680 genotype for FSHR is a factor of relative resistance to FSH stimulation resulting in slightly higher FSH serum levels, thus leading to a prolonged duration of the menstrual cycle. Moreover, some FSHR gene polymorphisms show a positive association with ovarian response to exogenous gonadotropin administration, hence exhibiting some potential for a pharmacogenetic estimation of the FSH dosage in controlled ovarian stimulation. The study of SNPs of the FSHR gene is an interesting field of research that could provide us with new information about the way each woman responds to exogenous gonadotropin administration during ovulation induction.

  19. Evaluation of chemotherapy response in ovarian cancer treatment using quantitative CT image biomarkers: a preliminary study

    NASA Astrophysics Data System (ADS)

    Qiu, Yuchen; Tan, Maxine; McMeekin, Scott; Thai, Theresa; Moore, Kathleen; Ding, Kai; Liu, Hong; Zheng, Bin

    2015-03-01

    The purpose of this study is to identify and apply quantitative image biomarkers for early prediction of the tumor response to the chemotherapy among the ovarian cancer patients participated in the clinical trials of testing new drugs. In the experiment, we retrospectively selected 30 cases from the patients who participated in Phase I clinical trials of new drug or drug agents for ovarian cancer treatment. Each case is composed of two sets of CT images acquired pre- and post-treatment (4-6 weeks after starting treatment). A computer-aided detection (CAD) scheme was developed to extract and analyze the quantitative image features of the metastatic tumors previously tracked by the radiologists using the standard Response Evaluation Criteria in Solid Tumors (RECIST) guideline. The CAD scheme first segmented 3-D tumor volumes from the background using a hybrid tumor segmentation scheme. Then, for each segmented tumor, CAD computed three quantitative image features including the change of tumor volume, tumor CT number (density) and density variance. The feature changes were calculated between the matched tumors tracked on the CT images acquired pre- and post-treatments. Finally, CAD predicted patient's 6-month progression-free survival (PFS) using a decision-tree based classifier. The performance of the CAD scheme was compared with the RECIST category. The result shows that the CAD scheme achieved a prediction accuracy of 76.7% (23/30 cases) with a Kappa coefficient of 0.493, which is significantly higher than the performance of RECIST prediction with a prediction accuracy and Kappa coefficient of 60% (17/30) and 0.062, respectively. This study demonstrated the feasibility of analyzing quantitative image features to improve the early predicting accuracy of the tumor response to the new testing drugs or therapeutic methods for the ovarian cancer patients.

  20. Why we may abandon basal follicle-stimulating hormone testing: a sea change in determining ovarian reserve using antimüllerian hormone.

    PubMed

    Toner, James P; Seifer, David B

    2013-06-01

    Antimüllerian hormone is the most informative serum marker of ovarian reserve currently available and should be considered an important part of any contemporary reproductive medicine practice. It is both more convenient and informative than basal FSH and can be assessed at any point in the cycle. It is the most useful serum method of determining ovarian reserve, which guides pretreatment counseling, choice of infertility treatment, and avoidance of ovarian hyperstimulation. The future role of basal FSH testing is in doubt.

  1. Application of X-Ray Fluorescence Analysis to Determine the Elemental Composition of Tissues from Different Ovarian Neoplasms

    NASA Astrophysics Data System (ADS)

    Motevich, I. G.; Strekal, N. D.; Papko, N. M.; Glebovich, M. I.; Shulha, A. V.; Maskevich, S. A.

    2015-03-01

    We present the results of x-ray fluorescence analysis of tissues from healthy ovaries and from ovaries with different pathologies: benign and borderline tumors, mucinous and endometrioid cancers, serous carcinomas. We determine the average copper, zinc, calcium, selenium, cadmium, lead, and mercury levels. We observed that in the benign ovarian tumors, we see a significant decrease in the cadmium, mercury, and lead levels compared with healthy tissues. In the borderline neoplasms, the copper level is reduced relative to zinc (Cu/Zn), cadmium, mercury, and lead, and also the zinc concentration is increased. In the ovarian carcinomas, we observed changes in the ratio of the chemical elements in the tumor tissues, depending on the histologic type. The results obtained can be used for differentiation, diagnosis, and adjustment of treatment for different ovarian neoplasms.

  2. Toll-Like Receptors Expression in Follicular Cells of Patients with Poor Ovarian Response

    PubMed Central

    Taghavi, Seyed Abdolvahab; Ashrafi, Mahnaz; Mehdizadeh, Mehdi; Karimian, Leili; Joghataie, Mohammad Taghi; Aflatoonian, Reza

    2014-01-01

    Background Poor ovarian response (POR) to gonadotropin stimulation has led to a significant decline in success rate of fertility treatment. The immune system may play an important role in pathophysiology of POR by dysfunctions of cytokines and the growth factor network, and the presence of ovarian auto-antibodies. The aim of this study is to investigate the expression of toll-like receptors (TLR) 1, 2, 4, 5, 6 and cyclooxygenase (COX) 2 genes in follicular cells and concentration of interleukin (IL)-6, IL-8 and macrophage migration inhibitory factor (MIF), as major parts of innate immunity, in follicular fluid (FF) obtained from POR women in comparison with normal women. Materials and Methods In this case-control study, 20 infertile POR patients and 20 normal women took part in this study and underwent controlled ovarian stimulation. The FF was obtained from the largest follicle (>18 mm). The FF was centrifuged and cellular pellet was then used for evaluation of expression of TLRs and COX2 genes by real-time PCR. FF was used for quantitative analysis for IL-6, IL-8 and MIF by enzyme-linked immunosorbent assay (ELISA). Results TLR1, 2, 4, 5, 6 and COX2 gene expression were significantly higher in POR (p<0.05). Concentration of IL-6, IL-8 and MIF proteins was significantly increased in POR compared with normal women (p<0.05). Conclusion These findings support the hypothesis that the immune system may be involved in pathophysiology of POR through TLRs. PMID:25083184

  3. Which cut-off value of serum anti-Müllerian hormone level can predict poor ovarian reserve, poor ovarian response to stimulation and in vitro fertilization success? A prospective data analysis.

    PubMed

    Ficicioglu, Cem; Cenksoy, Pinar Ozcan; Yildirim, Gazi; Kaspar, Cigdem

    2014-05-01

    The aim of our study is to demonstrate which cut-off value of serum anti-Müllerian hormone (AMH) level can predict poor ovarian reserve, poor ovarian response to stimulation and IVF outcomes. About 311 of 520 women enrolled IVF treatment cycle that meets inclusion criteria were recruited for this prospective data analysis. Data were collected for: age, duration of infertility, basal FSH and AMH level, total dosage of gonadotropins, maximum estradiol levels, duration of stimulations, total number of oocytes retrieved and clinical PR. Mean AMH was 1.76 ± 1.4 ng/ml and mean age was 33.25 ± 5.5 years. Clinical PR was 39.8% (n = 124). AMH was inversely correlated to total dosage of gonadotropins and age, AMH positively had a significant correlation with maximum estradiol levels, duration of stimulations and total number of oocytes retrieved. The patients in both categories of AMH levels, ≤0.5 and ≤1 ng/ml responded poorly to ovarian stimulation, had significantly higher total dosage of gonadotropins used and FSH levels on cycle day 3, lower maximum E2 levels and clinical PR. AMH could be an acceptable screening test in prediction of ovarian reserve, response to ovarian stimulation and PRs. AMH cut-off value ≤1 ng/ml may predict poor ovarian reserve, poor ovarian response to stimulation and IVF outcomes.

  4. Knockdown of ICB-1 gene enhanced estrogen responsiveness of ovarian and breast cancer cells.

    PubMed

    Konwisorz, Anna; Springwald, Anette; Haselberger, Martina; Goerse, Regina; Ortmann, Olaf; Treeck, Oliver

    2010-03-01

    ICB-1 chromosome 1 open reading frame 38 (C1orf38) is a human gene initially described by our group to be involved in differentiation processes of cancer cells. Recently, we have reported ICB-1 as a novel estrogen target gene and identified an estrogen response element in its promoter. In this study, we examined the role of ICB-1 in regulation of proliferation of breast and ovarian cancer cells. We knocked down its expression in estrogen-dependent MCF-7 breast cancer cells and hormone-unresponsive SK-OV-3 ovarian cancer cells by stable transfection with a specific shRNA plasmid followed by G-418 selection. Knockdown of ICB-1 enabled a considerable estrogen response of SK-OV-3 cells in terms of proliferation. This transformation of SK-OV-3 cells into an estrogen-responsive phenotype was accompanied by upregulation of estrogen receptor alpha (ERalpha) expression and a significant decrease of ERbeta expression on the mRNA level. Expression of ERalpha-dependent genes progesterone receptor, pS2, fibulin 1c, and c-fos was elevated in SK-OV-3 cells stably expressing ICB-1 shRNA. In MCF-7 cells, ICB-1 knockdown exerted similar effects on gene expression, supporting a general role of ICB-1 in estrogen responsiveness. Our data suggest that differentiation-associated gene ICB-1 might exert antagonistic actions on cellular estrogen response, which can result in inhibition of estradiol-triggered proliferation. The molecular mechanisms mediating this inhibitory effect of ICB-1 on estrogen signaling are suggested to be limitation of ERalpha transcript levels but sustaining high levels of ERbeta, reducing both activation of ERalpha target genes and cellular proliferation. The identification of ICB-1 as a new player in endocrine-related cancer encourages further studies on the significance of this gene in cancer development and therapy.

  5. Effect of high ovarian response on the expression of endocrine gland-derived vascular endothelial growth factor (EG-VEGF) in peri-implantation endometrium in IVF women

    PubMed Central

    Xu, Li-Zhen; Gao, Min-Zhi; Yao, Li-Hua; Liang, A-Juan; Zhao, Xiao-Ming; Sun, Zhao-Gui

    2015-01-01

    Objective: To investigate the effect of ovarian stimulation on the expression of EG-VEGF mRNA and protein in peri-implantation endometrium in women undergoing IVF and its relation with endometrial receptivity (ER). Design: Prospective laboratory study. Setting: University hospital. Patients: Eighteen women in stimulated cycles (SC) as study subjects and 18 women in natural cycles (NC) as controls. Women in SC group were classified with two subgroups, high ovarian response (SC1, n=9) with peak serum E2>5,000 pg/mL and moderate ovarian response (SC2, n=9) with peak serum E2 1,000-5,000 pg/mL. Intervention(s): Endometrial biopsies were collected 6 days after ovulation in NC or after oocyte retrieval in SC. Main outcome measure(s): Endometrium histological dating was observed with HE staining. EG-VEGF mRNA expression levels determined by real-time polymerase chain reaction analysis, and protein levels by immunohistochemistry. Results: All endometrial samples were in the secretory phase. The endometrial development in SC1 was 1 to 2 days advanced to NC, and with dyssynchrony between glandular and stromal tissue. Immunohistochemistry analysis showed that EG-VEGF protein was predominantly expressed in the glandular epithelial cells and endothelial cells of vessels, and also presented in the stroma. The image analysis confirmed that both the gland and stroma of endometrium in SC1 had a significantly lower EG-VEGF protein expression than that in SC2 and NC endometrium. Moreover, EG-VEGF mRNA levels were significantly lower in SC1 than in NC. Both EG-VEGF protein and mRNA levels had no significant difference between SC2 and NC. Conclusion: Decreased expression of EG-VEGF in the peri-implantation is associated with high ovarian response, which may account for the impaired ER and lower implantation rate in IVF cycles. PMID:26464631

  6. Serous ovarian carcinoma patients with high alpha-folate receptor had reducing survival and cytotoxic chemo-response.

    PubMed

    Chen, Yu-Li; Chang, Ming-Cheng; Huang, Chia-Yen; Chiang, Ying-Cheng; Lin, Han-Wei; Chen, Chi-An; Hsieh, Chang-Yao; Cheng, Wen-Fang

    2012-06-01

    The alpha-folate receptor (α-FR) is highly-expressed in various non-mucinous tumors of epithelial origin, including ovarian carcinoma. The aim of this study was to investigate the relationship between alpha-folate receptor (α-FR) and the clinico-pathologic features and outcomes of serous ovarian carcinoma patients and the possible mechanism of α-FR to chemo-resistance. Therefore, semi-quantitative reverse-transcription polymerase chain reactions for α-FR expression were performed in the 91 specimens of serous ovarian carcinomas. The expression of α-FR in each ovarian cancer tissue specimen was defined as the ratio of density of α-FR to density of glyceraldehyde-3-phosphate dehydrogenase (GAPDH). In vitro apoptotic experiments were tested in the original OVCAR-3 tumor cells and various OVCAR-3 α-FR-transfectants. Patients with an increased α-FR expression level had poorer responses to chemotherapy (per α-FR expression level increase: odds ratio (OR): 8.97 (95% confidence interval (CI): 1.40-57.36), p = 0.021). An increased α-FR expression level was an independently poor prognostic factor for disease free interval (DFI) (per α-FR expression level increase: hazard ratio (HR): 2.45 (95% CI: 1.16-5.18), p = 0.02) and had a negative impact on overall survival (OS) of these serous ovarian cancer patients (per α-FR expression level increase: HR: 3.6 (95% CI: 0.93-13.29), p = 0.03) by multivariate analyses. α-FR inhibited cytotoxic drug-induced apoptosis in our in vitro apoptotic assays. α-FR could induce chemo-resistance via regulating the expression of apoptosis-related molecules, Bcl-2 and Bax. Therefore, α-FR can be a potential biomarker for the prediction of chemotherapeutic responses and clinical prognosis. It also could be the target of ovarian cancer treatment.

  7. NF-κB-HOTAIR axis links DNA damage response, chemoresistance and cellular senescence in ovarian cancer

    PubMed Central

    Özeş, Ali R.; Miller, David F.; Özeş, Osman N.; Fang, Fang; Liu, Yunlong; Matei, Daniela; Huang, Tim; Nephew, Kenneth P.

    2016-01-01

    The transcription factor nuclear factor kappa B (NF-κB) and the long non-coding RNA (lncRNA) HOTAIR (HOX transcript antisense RNA) play diverse functional roles in cancer. In this study, we show that upregulation of HOTAIR induced platinum resistance in ovarian cancer, and increased HOTAIR levels were observed in recurrent platinum-resistant ovarian tumors vs. primary ovarian tumors. To investigate the role of HOTAIR during DNA damage induced by platinum, we monitored double-strand breaks and show that HOTAIR expression results in sustained activation of DNA damage response after platinum treatment. We demonstrate that ectopic expression of HOTAIR induces NF-κB activation during DNA damage response and MMP-9 and IL-6 expression, both key NF-κB target genes. We show that HOTAIR regulates activation of NF-κB by decreasing Iκ-Bα (NF-κB inhibitor) and establish that by inducing prolonged NF-κB activation and expression of NF-κB target genes during DNA damage, HOTAIR plays a critical role in cellular senescence and platinum sensitivity. Our findings suggest that a NF-κB-HOTAIR axis drives a positive-feedback loop cascade during DNA damage response and contributes to cellular senescence and chemotherapy resistance in ovarian and other cancers. PMID:27041570

  8. Plasma prorenin response to human chorionic gonadotropin in ovarian-hyperstimulated women: correlation with the number of ovarian follicles and steroid hormone concentrations.

    PubMed Central

    Itskovitz, J; Sealey, J E; Glorioso, N; Rosenwaks, Z

    1987-01-01

    Plasma prorenin and active renin were measured before and after human chorionic gonadotropin (hCG) administration in two groups of patients undergoing ovarian stimulation for 4-6 days with follicle-stimulating hormone alone or in combination with luteinizing hormone, for in vitro fertilization. Baseline total plasma renin (prorenin plus active renin; n = 12) averaged 25 +/- 8 ng/ml per hr (mean +/- SD). Total renin did not change during ovarian stimulation but it increased to 46 +/- 16 ng/ml per hr (P less than 0.05) 1 or 2 days later, just before hCG administration. Thirty-six hours after hCG administration, just before laparoscopy and egg retrieval, total renin was 123 +/- 97 ng/ml per hr; a peak of 182 +/- 143 ng/ml per hr occurred 2-6 days later--i.e., during the luteal phase of the menstrual cycle. In eight of the patients who did not conceive, total renin returned to baseline 14 days after hCG administration. In four who conceived, a nadir was reached (57 +/- 13 ng/ml per hr) 8-12 days after hCG administration and then total renin increased again as the plasma beta hCG measurement began to rise. By day 16 it averaged 225 +/- 157 ng/ml per hr. In a second group of five patients active renin and prorenin were measured separately. Active renin comprised less than 20% of the total renin at all times. It was unchanged until day 4 after hCG administration and then increased significantly only when plasma progesterone was high. Thus, the initial response to hCG was entirely due to an increase in prorenin. A highly significant correlation was observed between the number of follicles and the total renin increases on the day of aspiration (r = 0.93, P less than 0.001) and at the peak (r = 0.89, P less than 0.001). After hCG administration, a temporal relationship was observed between the rise in total renin and plasma estradiol and progesterone levels. These results demonstrate that plasma prorenin increases markedly after administration of hCG and that the rise is

  9. Significance of HE4 estimation in comparison with CA125 in diagnosis of ovarian cancer and assessment of treatment response

    PubMed Central

    2013-01-01

    Background Human epididymis protein 4 (HE4) is a novel and specific biomarker for ovarian cancer. The aim of this study is to evaluate a new tumor marker, HE4, in comparison with CA125 in diagnosis of epithelial ovarian cancer (EOC) and benign gynecological diseases. Methods CA125 and HE4 serum levels were determined in 30 patients with epithelial ovarian cancer (21 serous, 6 endometrioid and 3 mucinous tumors), 20 patients with benign gynecological diseases (8 patients with ovarian cyst, 5 patients with endometriosis, 4 patients with fibroid and 3 patients with pelvic inflammatory disease) and 20 healthy women. CA125 and HE4 cut-offs were 35 U/ml and 150 pmol/l, respectively. Results Serum HE4 and CA125 concentrations were significantly higher in the ovarian cancer patients compared with those seen in patients with benign disease or in the healthy controls (p = 0.001 and p < 0.001 respectively). In the receiver operating characteristic analysis (ROC), the area under the curve (AUC) values for HE4 was 0.96 (95% confidence interval, 0.9-1.0) and CA125 was 0.82 (95% confidence interval, 0.7-0.94). Compared to CA125, HE4 had higher sensitivity (90% vs. 83.3%), specificity (95% vs. 85%), PPV (93.1% vs. 80.7%) and NPV (92.7% vs. 87.2%), the combination of HE4 + CA125 the sensitivity and PPV reached 96.7% and 97% respectively. Conclusion Measuring serum HE4 concentrations along with CA125 concentrations may provide higher accuracy for detecting epithelial ovarian cancer. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1060413168685759 PMID:23343214

  10. Short-form Ron is a novel determinant of ovarian cancer initiation and progression

    PubMed Central

    Moxley, Katherine M.; Wang, Luyao; Welm, Alana L.; Bieniasz, Magdalena

    2016-01-01

    Short-form Ron (sfRon) is an understudied, alternative isoform of the full-length Ron receptor tyrosine kinase. In contrast to Ron, which has been shown to be an important player in many cancers, little is known about the role of sfRon in cancer pathogenesis. Here we report the striking discovery that sfRon expression is required for development of carcinogen-induced malignant ovarian tumors in mice. We also show that sfRon is expressed in several subtypes of human ovarian cancer including high-grade serous carcinomas, which is in contrast to no detectable expression in healthy ovaries. In addition, we report that introduction of sfRon into OVCAR3 cells resulted in epithelial-to-mesenchymal transition, activation of the PI3K and PDK1 pathway, and inhibition of the MAPK pathway. We demonstrated that sfRon confers an aggressive cancer phenotype in vitro characterized by increased proliferation and migration, and decreased adhesion of ovarian cancer cells. Moreover, the in vivo studies show that OVCAR3 tumors expressing sfRon exhibit significantly more robust growth and spreading to the abdominal cavity when compared with the parental sfRon negative OVCAR3 cells. These data suggest that sfRon plays a significant role in ovarian cancer initiation and progression, and may represent a promising therapeutic target for ovarian cancer treatment. PMID:27551332

  11. Phosphoramide mustard exposure induces DNA adduct formation and the DNA damage repair response in rat ovarian granulosa cells

    SciTech Connect

    Ganesan, Shanthi Keating, Aileen F.

    2015-02-01

    Phosphoramide mustard (PM), the ovotoxic metabolite of the anti-cancer agent cyclophosphamide (CPA), destroys rapidly dividing cells by forming NOR-G-OH, NOR-G and G-NOR-G adducts with DNA, potentially leading to DNA damage. A previous study demonstrated that PM induces ovarian DNA damage in rat ovaries. To investigate whether PM induces DNA adduct formation, DNA damage and induction of the DNA repair response, rat spontaneously immortalized granulosa cells (SIGCs) were treated with vehicle control (1% DMSO) or PM (3 or 6 μM) for 24 or 48 h. Cell viability was reduced (P < 0.05) after 48 h of exposure to 3 or 6 μM PM. The NOR-G-OH DNA adduct was detected after 24 h of 6 μM PM exposure, while the more cytotoxic G-NOR-G DNA adduct was formed after 48 h by exposure to both PM concentrations. Phosphorylated H2AX (γH2AX), a marker of DNA double stranded break occurrence, was also increased by PM exposure, coincident with DNA adduct formation. Additionally, induction of genes (Atm, Parp1, Prkdc, Xrcc6, and Brca1) and proteins (ATM, γH2AX, PARP-1, PRKDC, XRCC6, and BRCA1) involved in DNA repair were observed in both a time- and dose-dependent manner. These data support that PM induces DNA adduct formation in ovarian granulosa cells, induces DNA damage and elicits the ovarian DNA repair response. - Highlights: • PM forms ovarian DNA adducts. • DNA damage marker γH2AX increased by PM exposure. • PM induces ovarian DNA double strand break repair.

  12. Anti-ovarian tumor response of donor peripheral blood mononuclear cells is due to infiltrating cytotoxic NK cells

    PubMed Central

    Pandey, Veethika; Oyer, Jeremiah L.; Igarashi, Robert Y.; Gitto, Sarah B.; Copik, Alicja J.; Altomare, Deborah A.

    2016-01-01

    Treatment of ovarian cancer, a leading cause of gynecological malignancy, has good initial efficacy with surgery and platinum/taxane-based chemotherapy, but poor long-term survival in patients. Inferior long-term prognosis is attributed to intraperitoneal spreading, relapse and ineffective alternate therapies. Adoptive cell therapy is promising for tumor remission, although logistical concerns impede widespread implementation. In this study, healthy PBMCs were used to examine the immune response in a mouse model with human ovarian cancer, where natural killer (NK) cells were found to be the effector cells that elicited an anti-tumor response. Presence of tumor was found to stimulate NK cell expansion in mice treated intraperitoneally with PBMC+Interleukin-2 (IL-2), as compared to no expansion in non-tumor-bearing mice given the same treatment. PBMC+IL-2 treated mice exhibiting NK cell expansion had complete tumor remission. To validate NK cell mediated anti-tumor response, the intratumoral presence of NK cells and their cytotoxicity was confirmed by immunohistochemistry and granzyme activity of NK cells recovered from the tumor. Collectively, this study highlights the significance of NK cell-cytotoxic response to tumor, which may be attributed to interacting immune cell types in the PBMC population, as opposed to clinically used isolated NK cells showing lack of anti-tumor efficacy in ovarian cancer patients. PMID:26802025

  13. Anti-ovarian tumor response of donor peripheral blood mononuclear cells is due to infiltrating cytotoxic NK cells.

    PubMed

    Pandey, Veethika; Oyer, Jeremiah L; Igarashi, Robert Y; Gitto, Sarah B; Copik, Alicja J; Altomare, Deborah A

    2016-02-09

    Treatment of ovarian cancer, a leading cause of gynecological malignancy, has good initial efficacy with surgery and platinum/taxane-based chemotherapy, but poor long-term survival in patients. Inferior long-term prognosis is attributed to intraperitoneal spreading, relapse and ineffective alternate therapies. Adoptive cell therapy is promising for tumor remission, although logistical concerns impede widespread implementation. In this study, healthy PBMCs were used to examine the immune response in a mouse model with human ovarian cancer, where natural killer (NK) cells were found to be the effector cells that elicited an anti-tumor response. Presence of tumor was found to stimulate NK cell expansion in mice treated intraperitoneally with PBMC+Interleukin-2 (IL-2), as compared to no expansion in non-tumor-bearing mice given the same treatment. PBMC+IL-2 treated mice exhibiting NK cell expansion had complete tumor remission. To validate NK cell mediated anti-tumor response, the intratumoral presence of NK cells and their cytotoxicity was confirmed by immunohistochemistry and granzyme activity of NK cells recovered from the tumor. Collectively, this study highlights the significance of NK cell-cytotoxic response to tumor, which may be attributed to interacting immune cell types in the PBMC population, as opposed to clinically used isolated NK cells showing lack of anti-tumor efficacy in ovarian cancer patients.

  14. The effect of GnRH analogues for pituitary suppression on ovarian response in repeated ovarian stimulation cycles

    PubMed Central

    Cavagna, Mario; Paes de Almeida Ferreira Braga, Daniela; Biaggioni Lopes, Fabio; de Cássia Savio Figueira, Rita; Iaconelli, Assumpto; Borges, Edson

    2011-01-01

    Introduction Ovarian stimulation is employed in assisted reproduction techniques in order to obtain as many oocytes as possible. The early rise in oestradiol levels may lead to the premature end of the respective cycle. In order to avoid such an effect, pituitary suppression has been employed. The aim of this study was to evaluate whether maintenance or replacement of the type of GnRH analogue (i.e., agonist or antagonist) employed for pituitary suppression in the consecutive intracytoplasmic sperm injection (ICSI) cycle would negatively influence oocyte quality and ICSI outcome. Material and methods A retrospective observational study was conducted including 181 women with primary infertility. Patients were divided into four different groups according to the GnRH analogue used for pituitary suppression in the first and consecutive cycle. Results When a GnRH agonist was employed for pituitary suppression in the first cycle, the consecutive cycle showed comparable outcomes when performed with either a GnRH agonist or a GnRH antagonist. When the first cycle was performed with a GnRH antagonist, the use of the GnRH agonist in the successive cycle led to an increased number of oocytes retrieved (7.5% vs. 10.3%, p = 0.032) and the production of a higher number of embryos (4.5% vs. 6.3%, p = 0.036). Conclusions When the first cycle is carried out with a GnRH antagonist, the use of a GnRH agonist in the successive cycle would lead to increased numbers of oocytes collected and embryos produced. PMID:22295031

  15. A proteomic kinetic analysis of IGROV1 ovarian carcinoma cell line response to cisplatin treatment.

    PubMed

    Le Moguen, Karen; Lincet, Hubert; Marcelo, Paulo; Lemoisson, Edwige; Heutte, Natacha; Duval, Marilyne; Poulain, Laurent; Vinh, Joëlle; Gauduchon, Pascal; Baudin, Bruno

    2007-11-01

    Ovarian cancer is one of the leading causes of mortality by gynecological cancer. Despite good response to surgery and initial chemotherapy, essentially based on cisplatin (cis-diamino-dichloro-platinum(II) (CDDP)) compounds, frequent recurrences with chemoresistance acquisition are responsible for poor prognosis. Several mechanisms have been described as implicated in CDDP resistance, however they are not sufficient to exhaustively account for this resistance emergence. We applied a proteomic approach based on 2-DE coupled with MS (MALDI-TOF/TOF) to identify proteins associated with chemoresistance induced by CDDP. A kinetic analysis of IGROV1 cell behavior following treatment with CDDP and subsequent statistical analysis revealed time and/or concentration-dependent modifications in protein expression. We evidenced events such as decreased amino-acid and nucleotide synthesis potentially associated with cell cycle blockade, and variations that may be related to resistance acquisition, such as possible enhanced glycolysis and increased proliferating potential. Moreover, overexpressions of aldehyde dehydrogenase 1 and both cytokeratins 8 and 18 were consistent with our previous findings, demonstrating that expression of these proteins was increased in cisplatin-resistant IGROV1-R10 as compared to IGROV1 parental cells. Identification of such proteins could allow improved understanding of the mechanisms leading to cell death or survival and, thus, to the acquisition of chemoresistance.

  16. The role of HDAC2 in chromatin remodelling and response to chemotherapy in ovarian cancer

    PubMed Central

    Huang, Rui; Langdon, Simon P; Tse, Matthew; Mullen, Peter; Um, In Hwa; Faratian, Dana; Harrison, David J

    2016-01-01

    Chromatin undergoes structural changes in response to extracellular and environmental signals. We observed changes in nuclear morphology in cancer tissue biopsied after chemotherapy and hypothesised that these DNA damage-induced changes are mediated by histone deacetylases (HDACs). Nuclear morphological changes in cell lines (PE01 and PE04 models) and a xenograft model (OV1002) were measured in response to platinum chemotherapy by image analysis of nuclear texture. HDAC2 expression increased in PEO1 cells treated with cisplatin at 24h, which was accompanied by increased expression of heterochromatin protein 1 (HP1). HDAC2 and HP1 expression were also increased after carboplatin treatment in the OV1002 carboplatin-sensitive xenograft model but not in the insensitive HOX424 model. Expression of DNA damage response pathways (pBRCA1, γH2AX, pATM, pATR) showed time-dependent changes after cisplatin treatment. HDAC2 knockdown by siRNA reduced HP1 expression, induced DNA double strand breaks (DSB) measured by γH2AX, and interfered with the activation of DNA damage response induced by cisplatin. Furthermore, HDAC2 depletion affected γH2AX foci formation, cell cycle distribution, and apoptosis triggered by cisplatin, and was additive to the inhibitory effect of cisplatin in cell lines. By inhibiting expression of HDAC2, reversible alterations in chromatin patterns during cisplatin treatment were observed. These results demonstrate quantifiable alterations in nuclear morphology after chemotherapy, and implicate HDAC2 in higher order chromatin changes and cellular DNA damage responses in ovarian cancer cells in vitro and in vivo. PMID:26683361

  17. Ovarian Cancer

    MedlinePlus

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

  18. Younger poor ovarian response women achieved better pregnancy results in the first three IVF cycles.

    PubMed

    Yang, Yajuan; Sun, Xiuhua; Cui, Linlin; Sheng, Yan; Tang, Rong; Wei, Daimin; Qin, Yingying; Li, Weiping; Chen, Zi-Jiang

    2016-05-01

    This retrospective cohort study observed the live birth rates as well as cumulative live birth rates in women with poor ovarian response (POR) undergoing IVF-embryo transfer treatment, stratified for age and cycle number. Four hundred and one patients with POR diagnosed according to the Bologna criteria were enrolled and 700 IVF-ET cycles were analysed. The overall live-birth rate per cycle was 18.3%. From cycle 1 up to cycle 3, the live-birth rates decreased significantly from 22.2% to 11.1%. The live-birth rate fell to 2.4% in cycles 4 and over. When age advanced, the live birth rates decreased obviously (P < 0.01): 30.0% for women < 35 years old, 17.0% for those 35-40 years old, and 9.0% for women older than 40 years. Similarly, the cumulative live birth rates dropped from 48.0% (< 35 years) to 16.9% (≥ 40 years) accordingly. Younger patients (< 35 years old) with POR achieved better pregnancy results compared with patients of advanced age. Extremely low live-birth rates could be anticipated after three unsuccessful cycles; therefore it may not be appropriate to suggest more IVF cycles in POR women.

  19. Cellular and biomolecular responses of human ovarian cancer cells to cytostatic dinuclear platinum(II) complexes.

    PubMed

    Lin, Miaoxin; Wang, Xiaoyong; Zhu, Jianhui; Fan, Damin; Zhang, Yangmiao; Zhang, Junfeng; Guo, Zijian

    2011-03-01

    Polynuclear platinum(II) complexes represent a class of potential anticancer agents that have shown promising pharmacological properties in preclinical studies. The nature of cellular responses induced by these complexes, however, is poorly understood. In this research, the cellular responses of human ovarian cancer COC1 cells to dinuclear platinum(II) complexes {[cis-Pt(NH₃)₂Cl]₂L¹}(NO₃)₂ (1) and {[cis-Pt(NH₃)₂Cl]₂L²}(NO₃)₂ (2) (L¹ = α,α'-diamino-p-xylene, L² = 4,4'-methylenedianiline) has been studied using cisplatin as a reference. The effect of platinum complexes on the proliferation, death mode, mitochondrial membrane potential, and cell cycle progression has been examined by MTT assay and flow cytometry. The activation of cell cycle checkpoint kinases (CHK1/2), extracellular signal-regulated kinases (ERK1/2), and p38 mitogen-activated protein kinase (p38 MAPK) of the cells by the complexes has also been analyzed using phospho-specific flow cytometry. Complex 1 is more cytotoxic than complex 2 and cisplatin at most concentrations; complex 2 and cisplatin are comparably cytotoxic. These complexes kill the cells through an apoptotic or apoptosis-like pathway characterized by exposure of phosphatidylserine and dissipation of mitochondrial membrane potential. Complex 1 shows the strongest inductive effect on the morphological changes of the cells, followed by cisplatin and complex 2. Complexes 1 and 2 arrest the cell cycle in G2 or M phase, while cisplatin arrests the cell cycle in S phase. The influence of these complexes on CHK1/2, ERK1/2, and p38 MAPK varies with the dose of the drugs or reaction time. Activation of phospho-ERK1/2 and phospho-p38 MAPK by these complexes is closely related to the cytostatic activity. The results demonstrate that dinuclear platinum(II) complexes can induce some cellular responses different from those caused by cisplatin.

  20. Mink aging is associated with a reduction in ovarian hormone release and the response to FSH and ghrelin.

    PubMed

    Sirotkin, Alexander V; Mertin, Dušan; Süvegová, Karina; Lauričik, Jozef; Morovič, Martin; Harrath, Abdel Halim; Kotwica, Jan

    2016-09-15

    The endocrine mechanisms of mink ovarian hormones release and reproductive aging are poorly investigated. The aims of our study were to: (1) identify hormones produced by mink ovaries (the steroids progesterone [P] and estradiol [E], the peptide hormone oxytocin [OT], and the prostaglandin F [PGF] and prostaglandin E [PGE]); (2) examine the effect of FSH and ghrelin on the release of the hormones listed previously; and (3) understand whether these hormones can be involved in the control of mink reproductive aging, i.e., whether aging can be associated with changes (a) in the basal release of P, E, OT, PGF, or PGE and (b) their response to FSH and ghrelin. Fragments of ovaries of young (yearlings) and old (3-5 years of age) minks were cultured with and without FSH and ghrelin (0, 1, 10, or 100 ng/mL), and the release of hormones was analyzed by EIA/RIA. We found that isolated ovaries were able to release P, E, OT, PGF, and PGE, and the levels of P produced in the ovaries of old animals were lower than those produced in the ovaries of young animals, whereas the levels of other hormones did not differ. FSH was able to stimulate P and E and suppress OT and PGF and did not affect PGE release. Aging was associated with the inhibition of the effect of FSH on ovarian P and E, the appearance of the inhibitory action of FSH on OT, and the disappearance of this action on ovarian PGF. PGE was not affected by FSH, irrespective of animal age. Ghrelin was able to promote E (but not P) and suppress OT, PGF, and PGE output. Aging was associated with the appearance of an inhibitory influence of ghrelin on ovarian OT and PGE and with the disappearance of this influence on PGF output. Aging did not affect the action of ghrelin on ovarian P and E. Our observations (1) confirm the production of P and E and show that OT, PGF, and PGE are released from mink ovaries, (2) confirm the involvement of FSH and demonstrate the involvement of ghrelin in the control of mink ovarian hormone

  1. Genomic Markers of Ovarian Reserve

    PubMed Central

    Wood, Michelle A.; Rajkovic, Aleksandar

    2014-01-01

    Ovarian reserve and its utilization, over a reproductive life span, are determined by genetic, epigenetic, and environmental factors. The establishment of the primordial follicle pool and the rate of primordial follicle activation have been under intense study to determine genetic factors that affect reproductive lifespan. Much has been learned from transgenic animal models about the developmental origins of the primordial follicle pool and mechanisms that lead to primordial follicle activation, folliculogenesis, and the maturation of a single oocyte with each menstrual cycle. Recent genome-wide association studies on the age of human menopause have identified approximately 20 loci, and shown the importance of factors involved in double-strand break repair and immunology. Studies to date from animal models and humans show that many genes determine ovarian aging, and that there is no single dominant allele yet responsible for depletion of the ovarian reserve. Personalized genomic approaches will need to take into account the high degree of genetic heterogeneity, family pedigree, and functional data of the genes critical at various stages of ovarian development to predict women's reproductive life span. PMID:24101221

  2. Ovarian activity in the scimitar-horned oryx (Oryx dammah) determined by faecal steroid analysis.

    PubMed

    Morrow, C J; Monfort, S L

    1998-10-01

    Ultrasonography and radioimmunoassay (RIA) of serum oestradiol-17beta, luteinizing hormone (LH) and progesterone, and faecal oestrogen and progestin was used to assess ovarian activity in the scimitar-horned oryx (Oryx dammah). Ovarian examination using ultrasonography revealed maximal follicle and corpus luteum (CL) diameters of 15 and 32 mm, respectively. Steroid hormone metabolite distribution among individual faecal pellets within the same defaecation was relatively homogeneous with coefficients of variation averaging 10.2+/-1.8% and 16.2+/-4.6% for oestrogens and progestins, respectively. Elevated faecal oestrogen concentrations were associated with large (> 10 mm) antral follicles detected by ultrasonography. Periovulatory peaks in faecal oestrogen excretion, coincident with nadirs in progestin excretion, were detected in three females. Faecal progestin excretion exhibited a similar temporal pattern to serum progesterone concentrations, with a time lag of approximately 16 h. Faecal progestin concentrations corresponded with the presence of functional CL and proved useful for monitoring luteal function, spontaneous and prostaglandin-F2alpha analogue-induced luteolysis and anovulation. In summary, faecal steroid monitoring is a practical, noninvasive method for characterising ovarian steroid excretion and has potential for facilitating the application of assisted reproductive technologies in scimitar-horned oryx.

  3. Laparoscopic ovarian treatment in infertile patients with polycystic ovarian syndrome (PCOS): endocrine changes and clinical outcome.

    PubMed

    Liguori, G; Tolino, A; Moccia, G; Scognamiglio, G; Nappi, C

    1996-08-01

    During the years 1991-1994, 97 anovulatory infertile women with polycystic ovarian syndrome (PCOS) were treated with laparoscopic electrocautery of the ovarian surface after they had failed to ovulate under ovarian stimulation. To assess the endocrinological and clinical outcome and in an attempt to determine the mechanism of action, the serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), androstenedione, testosterone and dehydroepiandrosterone sulfate (DHEAS) were determined before and after laparoscopic ovarian cautery. Fifty regularly cycling women undergoing laparoscopy for investigation of infertility or tubal ligation served as controls. In patients with PCOS but not in controls, the reduction of androgen levels and normalization of cycle length were highly significant. In contrast, LH and FSH levels rose during the first 2 days after the operation. These results resemble those reported after ovarian wedge resection. Ovulation was obtained in 90% (81 of 90) and pregnancy in 81.1% (73 of 90) of the patients; that increased to 84.4%, including the non-responders (nine patients) treated with clomiphene citrate (CC), after electrocautery. The response to ovarian electrocautery was influenced by body weight, with an ovulation rate of 95-96% in the slim and moderately obese women, decreasing to 81-82% in the really obese ones. When ovulation was established, the pregnancy rate was independent of body weight. However, a striking relationship was detected between smoking habits and pregnancy rate subsequent to ovarian electrocautery, ranging from 24% in smokers to 92% in non-smoking couples. In 30 second-look operations, de novo adhesions were found in 23.3% of the patients (7 of 30). Therefore, ovarian electrocautery is an effective procedure to improve the intraovarian mechanism of selecting a dominant follicle for patients with PCOS in whom initial medical management fails, and it appears to be one of the possible treatments for this

  4. DNA methylation changes in epithelial ovarian cancer histotypes

    PubMed Central

    Earp, Madalene A.; Cunningham, Julie M.

    2016-01-01

    Survival after a diagnosis of ovarian cancer has not improved, and despite histological differences, treatment is similar for all cases. Understanding the molecular basis for ovarian cancer risk and prognosis is fundamental, and to this end much has been gleaned about genetic changes contributing to risk, and to a lesser extent, survival. There’s considerable evidence for genetic differences between the four pathologically defined histological subtypes; however, the contribution of epigenetics is less well documented. In this report, we review alterations in DNA methylation in ovarian cancer, focusing on histological subtypes, and studies examining the roles of methylation in determining therapy response. As epigenetics is making its way into clinical care, we review the application of cell free DNA methylation to ovarian cancer diagnosis and care. Finally, we comment on recurrent limitations in the DNA methylation literature for ovarian cancer, which can and should be addressed to mature this field. PMID:26363302

  5. Application of microwave-assisted micro-solid-phase extraction for determination of parabens in human ovarian cancer tissues.

    PubMed

    Sajid, Muhammad; Basheer, Chanbasha; Narasimhan, Kothandaraman; Choolani, Mahesh; Lee, Hian Kee

    2015-09-01

    Parabens (alkyl esters of p-hydroxybenzoic acid) are widely used as preservatives in food, cosmetics and pharmaceutical products. However, weak estrogenicity of some parabens has been reported in several studies, which provided the impetus for this work. Here, a simple and efficient analytical method for quantifying parabens in cancer tissues has been developed. This technique involves the simultaneous use of microwave-assisted solvent extraction (MASE) and micro-solid phase extraction (μ-SPE), in tandem with high performance liquid chromatography (HPLC/UV) analysis for the determination of parabens. The pollutants studied included four parabens (methyl, ethyl, propyl and butyl parabens). Optimization of the experimental parameters for MASE and μ-SPE was performed. Good relative standard deviation (%RSD) ranged from 0.09 to 2.81% and high enrichment factors (27-314) were obtained. Coefficients of determination (r(2)) up to 0.9962 were obtained across a concentration range of 5.0-200ngg(-1). The method detection limits for parabens ranged from 0.005 to 0.0244ngg(-1). The procedure was initially tested on prawn samples to demonstrate its feasibility on a complex biological matrix. Preliminary studies on human ovarian cancer (OC) tissues showed presence of parabens. Higher levels of parabens were detected in malignant ovarian tumor tissues compared to benign tumor tissue samples.

  6. Ovarian Fibrosis: A Phenomenon of Concern

    PubMed Central

    Zhou, Feng; Shi, Li-Bing; Zhang, Song-Ying

    2017-01-01

    Objective: Ovarian fibrosis is characterized by excessive proliferation of ovarian fibroblasts and deposition of extracellular matrix (ECM) and it is one of the principal reasons for ovarian dysfunction. This review aimed to investigate the pathogenetic mechanism of ovarian fibrosis and to clarify the relationship between ovarian diseases and fibrosis. Data Sources: We searched PubMed for English language articles published up to November 2016. The search terms included ovarian fibrosis OR fibrosis, ovarian chocolate cyst OR ovarian endometrioma, polycystic ovarian syndrome (PCOS), premature ovarian failure, ECM, matrix metalloproteinases (MMPs), tissue inhibitors of matrix metalloproteinases (TIMPs), transforming growth factor-beta 1 (TGF-β1), connective tissue growth factor (CTGF), peroxisome proliferator-activated receptor gamma (PPAR-γ), vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), and combinations of these terms. Study Selection: Articles were obtained and reviewed to analyze the pathogenic mechanism of ovarian fibrosis and related ovarian diseases. Results: Many cytokines, such as MMPs, TIMPs, TGF-β1, CTGF, PPAR-γ, VEGF, and ET-1, are involved in ovarian fibrogenesis. Ovarian fibrogenesis is associated with various ovarian diseases, including ovarian chocolate cyst, PCOS, and premature ovarian failure. One finding of particular interest is that fibrogenesis in peripheral tissues around an ovarian chocolate cyst commonly causes ovarian function diminution, and therefore, this medical problem should arouse widespread concern in clinicians worldwide. Conclusions: Patients with ovarian fibrosis are susceptible to infertility and tend to have decreased responses to assisted fertility treatment. Thus, protection of ovarian function should be a priority for women who wish to reproduce when making therapeutic decisions about ovarian fibrosis-related diseases. PMID:28139522

  7. P18/Stathmin1 is regulated by miR-31 in ovarian cancer in response to taxane

    PubMed Central

    Hassan, Mohamed Kamel; Watari, Hidemichi; Mitamura, Takashi; Mohamed, Zainab; EL-khamisy, Sherif F.; Ohba, Yusuke; Sakuragi, Noriaki

    2015-01-01

    MicroRNAs (miRNAs) have been reported to regulate the development of chemoresistance in many tumors. Stathmin 1 (STMN1) is a microtubule-depolymerizing molecule, involved in chemo-response; however, the mechanism of its regulation is unknown. Herein, the immunohistochemical study indicated significant upregulation of the STMN1 in the ovarian cancer tissues defined as resistant tumors compared with those defined as responsive tumors. STMN1 level elevated in the chemoresistant ovarian cancer cells, KF-TX, compared with the parental, KF, ones. Targeting STMN1 by siRNA restored taxane-sensitivity of KF-TX cells. Screening miRNA profiles from KF/KF-TX cellular set followed by bioinformatics-based prediction, revealed that miR-31 could be a possible regulator of STMN1. Down-modulation of miR-31 was verified by quantitative RT-PCR in the cellular set used. Overexpression of miR-31 in KF-TX cells (KF-TX-miR-31) significantly restored chemo-response and reduced STMN1 expression as well. STMN1 reduction-associated cellular characteristics such as enhanced microtubule polymerization and stability, as indicated by acetylated tubulin quantification, confocal visualization, and G2 phase delay, were observed in KF-TX-miR-31 cells, indicating the functional reduction of STMN1. miR-31 suppressed the luciferase activity in reporter construct containing the STMN1 3′-untranslated region (3′-UTR), confirming that miR-31 directly targets STMN1. miR-31 has therapeutic potency when introduced into ovarian cancer, in combination with taxane. PMID:25897432

  8. P18/Stathmin1 is regulated by miR-31 in ovarian cancer in response to taxane.

    PubMed

    Hassan, Mohamed Kamel; Watari, Hidemichi; Mitamura, Takashi; Mohamed, Zainab; El-Khamisy, Sherif F; Ohba, Yusuke; Sakuragi, Noriaki

    2015-01-01

    MicroRNAs (miRNAs) have been reported to regulate the development of chemoresistance in many tumors. Stathmin 1 (STMN1) is a microtubule-depolymerizing molecule, involved in chemo-response; however, the mechanism of its regulation is unknown. Herein, the immunohistochemical study indicated significant upregulation of the STMN1 in the ovarian cancer tissues defined as resistant tumors compared with those defined as responsive tumors. STMN1 level elevated in the chemoresistant ovarian cancer cells, KF-TX, compared with the parental, KF, ones. Targeting STMN1 by siRNA restored taxane-sensitivity of KF-TX cells. Screening miRNA profiles from KF/KF-TX cellular set followed by bioinformatics-based prediction, revealed that miR-31 could be a possible regulator of STMN1. Down-modulation of miR-31 was verified by quantitative RT-PCR in the cellular set used. Overexpression of miR-31 in KF-TX cells (KF-TX-miR-31) significantly restored chemo-response and reduced STMN1 expression as well. STMN1 reduction-associated cellular characteristics such as enhanced microtubule polymerization and stability, as indicated by acetylated tubulin quantification, confocal visualization, and G2 phase delay, were observed in KF-TX-miR-31 cells, indicating the functional reduction of STMN1. miR-31 suppressed the luciferase activity in reporter construct containing the STMN1 3'-untranslated region (3'-UTR), confirming that miR-31 directly targets STMN1. miR-31 has therapeutic potency when introduced into ovarian cancer, in combination with taxane.

  9. Maternal obesity leads to an inflammatory response and insulin resistance in ovarian tissue

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Maternal obesity during the pre-conception period may influence ovarian functions and affect embryo development. Lean and obese (OB) Sprague-Dawley dams were examined during the preimplantation period at dpc 4.5. Obesity was induced by controlled overfeeding (40% excess calories for 28 d) via total ...

  10. The evaluation of risk factors for failed response to conservative treatment in tubo-ovarian abscesses

    PubMed Central

    Akkurt, Mehmet Özgür; Yalçın, Serenat Eris; Akkurt, İltaç; Tatar, Burak; Yavuz, And; Yalçın, Yakup; Akgül, Mehmet Akif; Kayıkçıoğlu, Fulya

    2015-01-01

    Objective The aim of our study is to assess the risk factors for medical treatment failure and to predict the patients who will require the surgical therapy as well as to predict the factors affecting treatment success. Material and Methods This was a cross-sectional study including 76 women with tubo-ovarian abscesses (TOA) who were either conservatively or surgically treated and were admitted to two gynecology units over a 4-year period. The demographic characteristics of the patients, gynecologic and obstetric histories, size and localization of abscesses were recorded. Gentamicin plus clindamycin treatment protocol was implemented for all patients. Ampicillin treatment was added in three patients with the positive culture of Actinomyces. Response to treatment was evaluated after 48–72 h. Patients who fail to respond to medical treatment required surgery or percutaneous drainage. We compared clinical and laboratory factors between the groups. Results In surgery group, patients were significantly older than the others (44.9±5.4 versus 39.1±7.6 years). Fifty-six patients (74%) responded to antibiotics and 20 of the patients required surgical intervention. Patients treated with antibiotics were hospitalized for an average of 6.32±2.8 days versus 12.75±5.6 days for those who required surgery (p=0.021). Patients who were surgically treated had a mean size of TOA of 67.9±11.2 mm versus 53.6±9.4 mm for those treated with antibiotics alone (p=0.036). There were no significant differences between groups in laboratory parameters, except for initial white blood cell (WBC) counts. The complications of surgery included in descending order of frequency blood transfusions, surgical wound infections, bowel injury, and bladder injury. Conclusion An increased size of pelvic mass, higher initial WBC counts, advanced age, and smoking were all associated with failed response to conservative treatment. It is important to identify the risk factors to distinguish patients who

  11. A New Approach to Evaluate Drug Treatment Response of Ovarian Cancer Patients Based on Deformable Image Registration

    PubMed Central

    Tan, Maxine; Li, Zheng; Qiu, Yuchen; McMeekin, Scott D.; Thai, Theresa C.; Ding, Kai; Moore, Kathleen N.; Liu, Hong; Zheng, Bin

    2016-01-01

    Although Response Evaluation Criteria in Solid Tumors (RECIST) is the current clinical guideline to assess size change of solid tumors after therapeutic treatment, it has a relatively lower association to the clinical outcome of progression free survival (PFS) of the patients. In this paper, we presented a new approach to assess responses of ovarian cancer patients to new chemotherapy drugs in clinical trials. We first developed and applied a multi-resolution B-spline based deformable image registration method to register two sets of computed tomography (CT) image data acquired pre- and post-treatment. The B-spline difference maps generated from the co-registered CT images highlight the regions related to the volumetric growth or shrinkage of the metastatic tumors, and density changes related to variation of necrosis inside the solid tumors. Using a testing dataset involving 19 ovarian cancer patients, we compared patients’ response to the treatment using the new image registration method and RECIST guideline. The results demonstrated that using the image registration method yielded higher association with the six-month PFS outcomes of the patients than using RECIST. The image registration results also provided a solid foundation of developing new computerized quantitative image feature analysis schemes in the future studies. PMID:26336119

  12. The distribution of the apparent diffusion coefficient as an indicator of the response to chemotherapeutics in ovarian tumour xenografts.

    PubMed

    Tourell, Monique C; Shokoohmand, Ali; Landgraf, Marietta; Holzapfel, Nina P; Poh, Patrina S P; Loessner, Daniela; Momot, Konstantin I

    2017-02-21

    Diffusion-weighted magnetic resonance imaging (DW-MRI) was used to evaluate the effects of single-agent and combination treatment regimens in a spheroid-based animal model of ovarian cancer. Ovarian tumour xenografts grown in non-obese diabetic/severe-combined-immunodeficiency (NOD/SCID) mice were treated with carboplatin or paclitaxel, or combination carboplatin/paclitaxel chemotherapy regimens. After 4 weeks of treatment, tumours were extracted and underwent DW-MRI, mechanical testing, immunohistochemical and gene expression analyses. The distribution of the apparent diffusion coefficient (ADC) exhibited an upward shift as a result of each treatment regimen. The 99-th percentile of the ADC distribution ("maximum ADC") exhibited a strong correlation with the tumour size (r(2) = 0.90) and with the inverse of the elastic modulus (r(2) = 0.96). Single-agent paclitaxel (n = 5) and combination carboplatin/paclitaxel (n = 2) treatment regimens were more effective in inducing changes in regions of higher cell density than single-agent carboplatin (n = 3) or the no-treatment control (n = 5). The maximum ADC was a good indicator of treatment-induced cell death and changes in the extracellular matrix (ECM). Comparative analysis of the tumours' ADC distribution, mechanical properties and ECM constituents provides insights into the molecular and cellular response of the ovarian tumour xenografts to chemotherapy. Increased sample sizes are recommended for future studies. We propose experimental approaches to evaluation of the timeline of the tumour's response to treatment.

  13. The distribution of the apparent diffusion coefficient as an indicator of the response to chemotherapeutics in ovarian tumour xenografts

    PubMed Central

    Tourell, Monique C.; Shokoohmand, Ali; Landgraf, Marietta; Holzapfel, Nina P.; Poh, Patrina S. P.; Loessner, Daniela; Momot, Konstantin I.

    2017-01-01

    Diffusion-weighted magnetic resonance imaging (DW-MRI) was used to evaluate the effects of single-agent and combination treatment regimens in a spheroid-based animal model of ovarian cancer. Ovarian tumour xenografts grown in non-obese diabetic/severe-combined-immunodeficiency (NOD/SCID) mice were treated with carboplatin or paclitaxel, or combination carboplatin/paclitaxel chemotherapy regimens. After 4 weeks of treatment, tumours were extracted and underwent DW-MRI, mechanical testing, immunohistochemical and gene expression analyses. The distribution of the apparent diffusion coefficient (ADC) exhibited an upward shift as a result of each treatment regimen. The 99-th percentile of the ADC distribution (“maximum ADC”) exhibited a strong correlation with the tumour size (r2 = 0.90) and with the inverse of the elastic modulus (r2 = 0.96). Single-agent paclitaxel (n = 5) and combination carboplatin/paclitaxel (n = 2) treatment regimens were more effective in inducing changes in regions of higher cell density than single-agent carboplatin (n = 3) or the no-treatment control (n = 5). The maximum ADC was a good indicator of treatment-induced cell death and changes in the extracellular matrix (ECM). Comparative analysis of the tumours’ ADC distribution, mechanical properties and ECM constituents provides insights into the molecular and cellular response of the ovarian tumour xenografts to chemotherapy. Increased sample sizes are recommended for future studies. We propose experimental approaches to evaluation of the timeline of the tumour’s response to treatment. PMID:28220831

  14. The distribution of the apparent diffusion coefficient as an indicator of the response to chemotherapeutics in ovarian tumour xenografts

    NASA Astrophysics Data System (ADS)

    Tourell, Monique C.; Shokoohmand, Ali; Landgraf, Marietta; Holzapfel, Nina P.; Poh, Patrina S. P.; Loessner, Daniela; Momot, Konstantin I.

    2017-02-01

    Diffusion-weighted magnetic resonance imaging (DW-MRI) was used to evaluate the effects of single-agent and combination treatment regimens in a spheroid-based animal model of ovarian cancer. Ovarian tumour xenografts grown in non-obese diabetic/severe-combined-immunodeficiency (NOD/SCID) mice were treated with carboplatin or paclitaxel, or combination carboplatin/paclitaxel chemotherapy regimens. After 4 weeks of treatment, tumours were extracted and underwent DW-MRI, mechanical testing, immunohistochemical and gene expression analyses. The distribution of the apparent diffusion coefficient (ADC) exhibited an upward shift as a result of each treatment regimen. The 99-th percentile of the ADC distribution (“maximum ADC”) exhibited a strong correlation with the tumour size (r2 = 0.90) and with the inverse of the elastic modulus (r2 = 0.96). Single-agent paclitaxel (n = 5) and combination carboplatin/paclitaxel (n = 2) treatment regimens were more effective in inducing changes in regions of higher cell density than single-agent carboplatin (n = 3) or the no-treatment control (n = 5). The maximum ADC was a good indicator of treatment-induced cell death and changes in the extracellular matrix (ECM). Comparative analysis of the tumours’ ADC distribution, mechanical properties and ECM constituents provides insights into the molecular and cellular response of the ovarian tumour xenografts to chemotherapy. Increased sample sizes are recommended for future studies. We propose experimental approaches to evaluation of the timeline of the tumour’s response to treatment.

  15. A B-spline image registration based CAD scheme to evaluate drug treatment response of ovarian cancer patients

    NASA Astrophysics Data System (ADS)

    Tan, Maxine; Li, Zheng; Moore, Kathleen; Thai, Theresa; Ding, Kai; Liu, Hong; Zheng, Bin

    2016-03-01

    Ovarian cancer is the second most common cancer amongst gynecologic malignancies, and has the highest death rate. Since the majority of ovarian cancer patients (>75%) are diagnosed in the advanced stage with tumor metastasis, chemotherapy is often required after surgery to remove the primary ovarian tumors. In order to quickly assess patient response to the chemotherapy in the clinical trials, two sets of CT examinations are taken pre- and post-therapy (e.g., after 6 weeks). Treatment efficacy is then evaluated based on Response Evaluation Criteria in Solid Tumors (RECIST) guideline, whereby tumor size is measured by the longest diameter on one CT image slice and only a subset of selected tumors are tracked. However, this criterion cannot fully represent the volumetric changes of the tumors and might miss potentially problematic unmarked tumors. Thus, we developed a new CAD approach to measure and analyze volumetric tumor growth/shrinkage using a cubic B-spline deformable image registration method. In this initial study, on 14 sets of pre- and post-treatment CT scans, we registered the two consecutive scans using cubic B-spline registration in a multiresolution (from coarse to fine) framework. We used Mattes mutual information metric as the similarity criterion and the L-BFGS-B optimizer. The results show that our method can quantify volumetric changes in the tumors more accurately than RECIST, and also detect (highlight) potentially problematic regions that were not originally targeted by radiologists. Despite the encouraging results of this preliminary study, further validation of scheme performance is required using large and diverse datasets in future.

  16. Determination of ovarian cyclicity and pregnancy using fecal progesterone in forest musk deer (Moschus berezovskii).

    PubMed

    Wang, Yi-Hua; Liu, Shu-Qiang; Yang, Shuang; Zhang, Tian-Xiang; Wei, Yu-Ting; Zhou, Jun-Tong; Hu, De-Fu; Li, Lin-Hai

    2016-07-01

    The forest musk deer (FMD, Moschus berezovskii) is a threatened species in China. Although crucial for its artificial breeding management and thus protection, to date, gonadal steroidogenic activity data are unavailable in this species. Thus, the objectives of the present study were to characterize ovarian activity throughout the estrous cycle, non-pregnant luteal phase, and gestation in female FMD. These goals were accomplished using an enzyme immunoassay to measure fecal concentrations of estradiol (E2) and progesterone. Fecal samples were collected from female FMD (aged 3-4 years) for one year, including during breeding and non-breeding seasons. Non-pregnant estrous cycles were recorded in females, based on fecal progesterone concentrations, their overall estrous cycle length was (mean±SEM) 24.3±0.5 days, with 21.6±0.5 days in the luteal phase and 2.7±0.3 days in the inter-luteal phase. Fecal progesterone and E2 concentrations were also measured in females that became pregnant and gave birth after gestating approximately 6 months. Two weeks after becoming pregnant, the average fecal progesterone concentration was significantly greater than that during non-pregnancy. The average fecal progesterone concentrations during pregnancy increased 3.2-fold above non-pregnant concentrations, decreasing to non-pregnant concentrations only after parturition. By contrast, average fecal E2 concentrations during gestation and after parturition were not different from average non-pregnant concentration. In addition, no difference was observed between progesterone concentration in the first month after pregnancy and the value during the luteal phase. However, progesterone concentration during the second month of pregnancy was significantly higher than the value during the luteal phase. In conclusion, monitoring fecal progesterone is an effective method for assessing ovarian function in FMD and will be a useful tool for breeding management and development of assisted

  17. Ovarian Cyst

    MedlinePlus

    ... accurate way to tell if a woman has ovarian cancer. For example, some women who do have ovarian cancer have a normal CA-125 level. Also, this ... for women who show signs or symptoms of ovarian cancer or who have genetic mutations that increase the ...

  18. Identification of Anti-CA125 Antibody Responses in Ovarian Cancer Patients by a Novel Deep Sequence-Coupled Biopanning Platform.

    PubMed

    Frietze, Kathryn M; Roden, Richard B S; Lee, Ji-Hyun; Shi, Yang; Peabody, David S; Chackerian, Bryce

    2016-02-01

    High-grade epithelial ovarian cancer kills more women than any other gynecologic cancer and is rarely diagnosed at an early stage. We sought to identify tumor-associated antigens (TAA) as candidate diagnostic and/or immunotherapeutic targets by taking advantage of tumor autoantibody responses in individuals with ovarian cancer. Plasma-derived IgG from a pool of five patients with advanced ovarian cancer was subjected to iterative biopanning using a library of bacteriophage MS2 virus-like particles (MS2-VLPs) displaying diverse short random peptides. After two rounds of biopanning, we analyzed the selectant population of MS2-VLPs by Ion Torrent deep sequencing. One of the top 25 most abundant peptides identified (DISGTNTSRA) had sequence similarity to cancer antigen 125 (CA125/MUC16), a well-known ovarian cancer-associated antigen. Mice immunized with MS2-DISGTNTSRA generated antibodies that cross-reacted with purified soluble CA125 from ovarian cancer cells but not membrane-bound CA125, indicating that the DISGTNTSRA peptide was a CA125/MUC16 peptide mimic of soluble CA125. Preoperative ovarian cancer patient plasma (n = 100) was assessed for anti-DISGTNTSRA, anti-CA125, and CA125. Patients with normal CA125 (<35 IU/mL) at the time of diagnosis had significantly more antibodies to DISGTNTSRA and to CA125 than those patients who had high CA125 (>35 IU/mL). A statistically significant survival advantage was observed for patients who had either normal CA125 and/or higher concentrations of antibodies to CA125 at the time of diagnosis. These data show the feasibility of using deep sequence-coupled biopanning to identify TAA autoantibody responses from cancer patient plasma and suggest a possible antibody-mediated mechanism for low CA125 plasma concentrations in some ovarian cancer patients.

  19. Ovarian dynamics in response to two modified intravaginal progesterone releasing device and oestradiol benzoate based ovulation synchronisation protocols designed for use in Brahman heifers.

    PubMed

    Edwards, S A A; Atkinson, P C; Satake, N; Boe-Hansen, G; McGowan, M R

    2014-07-01

    The objective was to investigate the ovarian response of Brahman heifers to two modified ovulation synchronisation protocols developed to increase the proportion of normal synchronous ovulations. Experiment 1 characterised the growth of the ovulatory follicle in heifers (n=19) treated with an intravaginal progesterone releasing device (IPRD) and oestradiol benzoate (ODB), to determine the optimal time to induce ovulation. Using the findings from Experiment 1, Experiment 2 investigated the effect of reducing the duration of IPRD insertion and increasing the interval from IPRD removal to ODB treatment (modified protocol 1 - OPO-6; n=20), and omitting ODB treatment at the time of IPRD insertion (modified protocol 2 - PO-6; n=20). An IPRD (0.78 g progesterone) was inserted at Day 0 (OPO-8) or Day 2 (OPO-6 and PO-6) and all heifers also received 1 mg ODB i.m. Day 8: IPRD removed + 500 μg cloprostenol i.m. At 24 h (OPO-8) and 36 h (OPO-6 and PO-6) post IPRD removal: 1 mg ODB i.m. Fixed-time AI (FTAI) occurred at 54 h for OPO-8 and 72 h for OPO-6 and PO-6, post IPRD removal. After IPRD treatment all OPO-6 and OPO-8 heifers initiated a new follicular wave whereas 25% of PO-6 heifers failed. Diameter of the dominant follicle was larger at FTAI in the PO-6 (11.34 ± 0.50 mm) compared to the OPO-8 protocol (9.74 ± 0.51 mm; P<0.05), but similar to the OPO-6 protocol (10.52 ± 0.51 mm). Proportion of ovulations occurring 12 h prior and 24 h post FTAI was similar for the PO-6 (80%) and OPO-6 (75%) protocols but numerically lower in the OPO-8 heifers (60%). The apparent improvement in ovarian response in heifers treated with the modified protocols needs to be confirmed in larger field studies.

  20. Quantitative proteomics analysis integrated with microarray data reveals that extracellular matrix proteins, catenins, and p53 binding protein 1 are important for chemotherapy response in ovarian cancers.

    PubMed

    Pan, Sheng; Cheng, Lihua; White, James T; Lu, Wei; Utleg, Angelita G; Yan, Xiaowei; Urban, Nicole D; Drescher, Charles W; Hood, Leroy; Lin, Biaoyang

    2009-08-01

    Chemotherapy with carboplatin and paclitaxel is the standard treatment for ovarian cancer patients. Although most patients initially respond to this treatment, few are cured. Resistance to chemotherapy is the major cause of treatment failure. We applied a quantitative proteomic approach based on ICAT/MS/MS technology to analyze tissues harvested at primary debulking surgery before the initiation of combination chemotherapy in order to identify potential naive or intrinsic chemotherapy response proteins in ovarian cancers. We identified 44 proteins that are overexpressed, and 34 proteins that are underexpressed in the chemosensitive tissue compared to the chemoresistant tissue. The overexpressed proteins identified in the chemoresistant tissue include 10 proteins (25.6%) belonging to the extracellular matrix (ECM), including decorin, versican, basigin (CD147), fibulin-1, extracellular matrix protein 1, biglycan, fibronectin 1, dermatopontin, alpha-cardiac actin (smooth muscle actin), and an EGF-containing fibulin-like extracellular matrix protein 1. Interesting proteins identified as overexpressed in the chemosensitive tissue include gamma-catenin (junction plakoglobin) and delta-catenin, tumor suppressor p53-binding protein 1 (53BP1), insulin-like growth factor-binding protein 2 (IGFBP2), proliferating cell nuclear antigen (PCNA), annexin A11, and 53 kDa selenium binding protein 1. Integrative analysis with expression profiling data of eight chemoresistant tissues and 13 chemosensitive tissues revealed that 16 proteins showed consistent changes at both the protein and the RNA levels. These include P53 binding protein 1, catenin delta 1 and plakoglobin, EGF-containing fibulin-like extracellular matrix protein 1 and voltage-dependent anion-selective channel protein 1. Our results suggest that chemotherapy response may be determined by multiple and complex system properties involving extracellular-matrix, cell adhesion and junction proteins.

  1. Ricinus communis L. stem bark extracts regulate ovarian cell functions and secretory activity and their response to Luteinising hormone.

    PubMed

    Nath, S; Kadasi, A; Grossmann, R; Sirotkin, A V; Kolesarova, A; Talukdar, A D; Choudhury, M D

    2015-01-01

    Ricinus communis L. has ethnopharmacological contraceptive reputation but its stem bark has unexplored mechanisms of action in female reproductive system. In the present study, the effect of methanolic and aqueous extracts from the stem bark of the plant was examined on basic porcine ovarian granulosa cell functions and its response to Luteinising hormone (LH)-the upstream hormonal regulator. Systemic treatment of methanolic and aqueous extracts stimulated cell proliferation (proliferating cell nuclear antigen, PCNA) and also promoted cell apoptosis (caspase-3). Aqueous extract has inverted the stimulatory effect of LH on PCNA but not on caspase-3. Methanolic extract stimulated as well as inhibited progesterone release and stimulated testosterone secretion. Whereas aqueous extract inhibited both steroid releases and suppressed the stimulatory effect of LH on progesterone release and promoted the inhibitory effect of LH on testosterone release. In conclusion, the present study unveils the mechanism of action of R. communis stem bark in in vitro condition. These suggest its possible contraceptive efficacy by exerting its regulatory role over LH and on basic ovarian cell functions and secretion activity.

  2. Morphokinetic Characteristics and Developmental Potential of In Vitro Cultured Embryos from Natural Cycles in Patients with Poor Ovarian Response

    PubMed Central

    Hojnik, N.; Vlaisavljević, V.

    2016-01-01

    Background. Patients with poor ovarian response to ovarian hyperstimulation represent an interesting group for studying the impact of embryo cleavage irregularities on clinical outcome since all embryos, regardless of their quality, are usually transferred to the uterus. The aim of our study was to follow the morphokinetics of fertilized oocytes from natural cycles in poor responders. Methods. Zygotes from 53 cycles were cultured in vitro for 3 days. The morphokinetics of their development and transfer outcomes were retrospectively analyzed for the normally and irregularly cleaved embryos. Results. Of all embryos, 30.2% had single and 20.8% multiple cleavage irregularities with the following prevalence: developmental arrest 30.2%, direct cleavage to more than two cells 24.5%, chaotic cleavage 13.2%, and reverse cleavage 11.3%. These embryos had longer pronuclear phases, first cytokinesis, second embryo cell cycles, and less synchronized divisions. The transfer of normally developing embryos resulted in an implantation rate of 30.8% and a delivery rate of 23.1%, but irregularly cleaved embryos did not implant. Conclusions. The use of time-lapse microscopy in poor responder patients identified embryos with cleavage abnormalities that are related with no or extremely low implantation potential. Gained information about embryo quality is important for counselling patients about their expectations. PMID:28097133

  3. Soft Determinism plus Awareness Equals Shared Responsibility

    ERIC Educational Resources Information Center

    Rousseve, Ronald J.

    1971-01-01

    This article seeks to present a viable resolution of one of the perennial ideological issues in counseling: determinism versus human freedom. The dilemma has bearing on the related professional issue of client and counselor responsibility. (Author)

  4. Reproductive responses of dairy cows with ovarian cysts to simultaneous human chorionic gonadotropin or gonadotropin-releasing hormone and cloprostenol compared to gonadotropin-releasing hormone alone treatment

    PubMed Central

    Taktaz, T.; Kafi, M.; Mokhtari, Adel; Heidari, M.

    2015-01-01

    Aim: Bovine ovarian cysts are a common cause of economic loss in modern dairy herds. The objective of the present study was to evaluate the reproductive responses to three protocols using hCG, GnRH and cloprostenol when the definite diagnosis of the type of ovarian cyst is/is not possible in dairy cows. Materials and Methods: A total of 144 lactating dairy cows with ovarian cysts were divided into three groups. At diagnosis (Day 0), cows in Group 1 (the conventional method, n=47) were injected with 0.02 mg of a GnRH analogue i.m. (Buserelin); cows in Group 2 (n=47) were intramuscularly treated with 0.02 mg Buserelin plus 500 µg cloprostenol; and cows in Group 3 (n=50) were intramuscularly treated with 1500 IU hCG plus 500 µg cloprostenol. All cows received 500 µg cloprostenol intramuscularly on Day 10. Results: No statistically significant differences were found in the recovery time, interval to conception, conception rate at first AI, and pregnancy rates by Days 70 and 100 after treatment among the three groups. Conclusions: Simultaneous treatment of ovarian cysts with hCG or GnRH and cloprostenol appeared to have no advantage over the conventional method, GnRH alone, in dairy cows. Furthermore, hCG and GnRH have an equal therapeutic effect in cows with ovarian cysts. PMID:27047149

  5. Genetic Variants in MicroRNA Biosynthesis Pathways and Binding Sites Modify Ovarian Cancer Risk, Survival, and Treatment Response

    PubMed Central

    Liang, Dong; Meyer, Larissa; Chang, David W.; Lin, Jie; Pu, Xia; Ye, Yuanqing; Gu, Jian; Wu, Xifeng; Lu, Karen

    2017-01-01

    MicroRNAs (miRNA) play important roles in tumorigenesis. Genetic variations in miRNA processing genes and miRNA binding sites may affect the biogenesis of miRNA and the regulatory effect of miRNAs to their target genes, hence promoting tumorigenesis. This study analyzed 226 single nucleotide polymorphisms (SNP) in miRNA processing genes and miRNA binding sites in 339 ovarian cancer cases and 349 healthy controls to assess association with cancer risk, overall survival, and treatment response. Thirteen polymorphisms were found to have significant association with risk. The most significant were 2 linked SNPs (r2 = 0.99), rs2740351 and rs7813 in GEMIN4 [odds ratio (OR) = 0.71; 95% confidence interval (CI), 0.57–0.87 and OR = 0.71; 95% CI, 0.57–0.88, respectively]. Unfavorable genotype analysis showed the cumulative effect of these 13 SNPs on risk (P for trend < 0.0001). Potential higher order gene–gene interactions were identified, which categorized patients into different risk groups according to their genotypic signatures. In the clinical outcome study, 24 SNPs exhibited significant association with overall survival and 17 SNPs with treatment response. Notably, patients carrying a rare homozygous genotype of rs1425486 in PDGFC had poorer overall survival [hazard ratio (HR) = 2.69; 95% CI, 1.67–4.33] and worse treatment response (OR = 3.38; 95% CI, 1.39–8.19), compared to carriers of common homozygous and heterozygous genotypes. Unfavorable genotype analyses also showed a strong gene-dosage effect with decreased survival and increased risk of treatment nonresponse in patients with greater number of unfavorable genotypes (P for trend < 0.0001). Taken together, miRNA-related genetic polymorphisms may impact ovarian cancer predisposition and clinical outcome both individually and jointly. PMID:21118967

  6. Current Approaches and Challenges in Managing and Monitoring Treatment Response in Ovarian Cancer

    PubMed Central

    Marcus, Charlotte S; Maxwell, G Larry; Darcy, Kathleen M; Hamilton, Chad A; McGuire, William P

    2014-01-01

    Epithelial ovarian cancer is the leading cause of death among gynecologic malignancies. Treatment of recurrent ovarian cancer remains a challenge despite advances in surgical and chemotherapeutic options. A goal of many providers is to detect recurrences as early as possible and initiate treatment though there is controversy as to whether this impacts outcome. Elevations in CA125 and radiological findings may precede symptoms of recurrence by several months. While detection of recurrences by physical exam alone is unusual, a thorough exam in conjunction with reported symptoms and elevated CA125 is sufficient to detect 80-90% of recurrences. A spiral CT scan may be used to confirm recurrence in the setting of asymptomatic CA125 elevation and a PET/CT can yield additional insight if the CT is inconclusive. Initiating chemotherapy prior to the development of symptoms, even in the setting of elevated CA125, does not impact overall survival primarily because the efficacy of available treatments in the recurrent setting is poor. More information about tumor biology and ways to predict which patients will benefit from available treatment options is required. Consequently, the approach to post-treatment surveillance should be individualized taking into account the clinical benefit of the second-line therapy, versus the costs and morbidity of the surveillance method. PMID:24396495

  7. Ovarian responses in Bos indicus heifers treated to synchronise ovulation with intravaginal progesterone releasing devices, oestradiol benzoate, prostaglandin F(2α) and equine chorionic gonadotrophin.

    PubMed

    Butler, S A A; Phillips, N J; Boe-Hansen, G B; Bo, G A; Burns, B M; Dawson, K; McGowan, M R

    2011-12-01

    The objectives were: (i) improve understanding of the ovarian responses of Bos indicus heifers treated with different ovulation synchronisation protocols, (ii) compare ovarian responses of B. indicus heifers treated with intravaginal progesterone releasing device (IPRD)+oestradiol benzoate (ODB) versus a conventional prostaglandin F(2α) (PGF(2α)) protocol and (iii) investigate whether reducing the amount of progesterone (P(4)) in the IPRD, and treatment with equine chorionic gonadotrophin (eCG) would increase the proportion of heifers with normal ovarian function during the synchronised and return cycles. Two-year-old Brahman (n=30) and Brahman-cross (n=34) heifers were randomly allocated to three IPRD-treatment groups: (i) standard-dose IPRD (Cue-Mate(®) 1.56g P(4); n=17); (ii) half-dose IPRD (Cue-Mate(®) 0.78g P(4); n=15); (iii) half-dose IPRD+300IU eCG at IPRD removal (n=14), and a non-IPRD control group (iv) 2×PGF(2α) (500μg cloprostenol) on Days -16 and -2 (n=18). IPRD-treated heifers received 250μg cloprostenol at IPRD insertion (Day -10) and IPRD removal (Day -2) and 1mg ODB on Days -10 and -1. Ovarian function was evaluated by ultrasonography and plasma P(4) throughout the synchronised and return cycles. The mean diameter of the dominant follicle observed at 54-56h after IPRD removal, was greater for heifers which ovulated than heifers which did not ovulate (P<0.001; 14.5±1.1 vs. 9.3±0.6mm, respectively). The prevalence of IPRD-treated heifers with ovarian dysfunction (persistent CL, failure to re-ovulate, shortened luteal phase) was 39%. This relatively high prevalence of ovarian dysfunction may explain the commonly reported, lower than expected pregnancy rates to FTAI in B. indicus heifers treated to synchronise ovulation.

  8. Ovarian Tumor (OTU)-domain Containing Viral Proteases Evade Ubiquitin- and ISG15-dependent Innate Immune Responses

    PubMed Central

    Frias-Staheli, Natalia; Giannakopoulos, Nadia V.; Kikkert, Marjolein; Taylor, Shannon L.; Bridgen, Anne; Paragas, Jason J.; Richt, Juergen A.; Rowland, Raymond R.; Schmaljohn, Connie S.; Lenschow, Deborah J.; Snijder, Eric J.; García-Sastre, Adolfo; Virgin, Herbert Whiting

    2007-01-01

    Summary Ubiquitin (Ub) and interferon stimulated gene product 15 (ISG15) reversibly conjugate to proteins via a conserved LRLRGG C-terminal motif, mediating important innate antiviral responses. The ovarian tumor (OTU) domain represents a superfamily of predicted proteases found in eukaryotic, bacterial and viral proteins, some of which have Ub-deconjugating activity. We show that the OTU domain-containing proteases of nairoviruses and arteriviruses hydrolyze Ub and ISG15 from cellular target proteins. This broad activity contrasts with the target specificity of known mammalian OTU domain-containing proteins. The biological significance of this activity of viral OTU domain-containing proteases was evidenced by their capacity to inhibit NF-κB dependent signaling and to antagonize the antiviral effects of ISG15 during Sindbis virus infection in vivo. The deconjugating activity of viral OTU proteases represents a novel viral immune evasion mechanism that inhibits Ub-and ISG15-dependent antiviral pathways. PMID:18078692

  9. The effect of age on the ovarian response to gonadotropin and on pregnancy rate in polycystic ovary syndrome.

    PubMed

    Guido, M; Belosi, C; Selvaggi, L; Lattanzi, F; Apa, R; Fulghesu, A M; Lanzone, A

    2003-06-01

    Recent studies have proposed that, in women affected by the polycystic ovary syndrome (PCOS), aging is able to regularize the menstrual cyclicity. To evaluate the ovarian response in PCOS patients according to their age, we studied 33 PCOS patients, 20 of whom with an age ranging from 28 to 34 years (younger PCOS) and 13 ranging from 35 to 45 years (older PCOS). All patients underwent an ovulation induction therapeutic protocol with low-dose recombinant follicle stimulating hormone, for a total of 80 cycles (44 cycles for the younger PCOS group and 36 cycles for the older PCOS group). No significant difference was found between the days of therapy (12.3 +/- 5.4 vs. 13.5 +/- 5.6 days), total amount of drugs (980.7 +/- 568.9 IU vs. 1063.9 +/- 469.5 IU) or ovulation rate (93% vs. 89%) in the two groups. The two groups showed a significant difference in the maximum estradiol level (2053.5 +/- 1497.2 vs. 1269.0 +/- 911.5 pmol/l, p < 0.01), the number of the recruited and preovulatory follicles (1.7 +/- 2.5 vs. 0.64 +/- 0.9, p < 0.05 and 1.7 +/- 1.1 vs. 1.2 +/- 0.5, p < 0.01, respectively) and the pregnancy rate (36% vs. 14%, p < 0.05). In conclusion, our data clearly showed that, also in PCOS, advanced age is a negative prognostic factor in the ovarian response to ovulation induction therapies.

  10. Family History of Breast Cancer as a Determinant of the Risk of Developing Endometrial and Ovarian Cancers: A Nationwide Cohort Study

    DTIC Science & Technology

    2002-01-01

    associated with reduced risk. Aside from its association with hereditary nonpolyposis colorectal cancer (HNPCC), and probably Cowden=s syndrome , the...HBOC) syndrome (Lynch et al., 1981; Prior and Waterhouse, 1981). Inherited mutations in the genes BRCA1 and BRCA2 are responsible for most (80-90...addressed familial aggregations of breast cancer and ovarian cancer and, in the context of the HBOC syndrome , a shared genetic etiology has been

  11. Biological Basis for Chemoprevention of Ovarian Cancer

    DTIC Science & Technology

    2000-10-01

    Since reduction of ovulation is protective against ovarian cancer, prevention may represent a feasible approach to decreasing mortality . To achieve a...potent apoptotic effect on ovarian epithelial cells, the use of levonorgestrel in chemoprevention of ovarian cancer is being explored in chickens and women...A chemoprevention trial is ongoing in chickens and we will begin a trial to determine whether levonorgestrel induces apoptosis in the ovarian epithelium of women undergoing oophorectomy.

  12. Ovarian Cancer

    MedlinePlus

    ... factors may increase a woman’s risk for ovarian cancer: • Being middle-aged or older. • Having close family members (such as ... than 40, with the greatest number of ovarian cancers occurring in women aged 60 years or older. Each year, approximately 21, ...

  13. Determination of the spectral dependence of reduced scattering and quantitative second-harmonic generation imaging for detection of fibrillary changes in ovarian cancer

    NASA Astrophysics Data System (ADS)

    Campbell, Kirby R.; Tilbury, Karissa B.; Campagnola, Paul J.

    2015-03-01

    Here, we examine ovarian cancer extracellular matrix (ECM) modification by measuring the wavelength dependence of optical scattering measurements and quantitative second-harmonic generation (SHG) imaging metrics in the range of 800-1100 nm in order to determine fibrillary changes in ex vivo normal ovary, type I, and type II ovarian cancer. Mass fractals of the collagen fiber structure is analyzed based on a power law correlation function using spectral dependence measurements of the reduced scattering coefficient μs' where the mass fractal dimension is related to the power. Values of μs' are measured using independent methods of determining the values of μs and g by on-axis attenuation measurements using the Beer-Lambert Law and by fitting the angular distribution of scattering to the Henyey-Greenstein phase function, respectively. Quantitativespectral SHG imaging on the same tissues determines FSHG/BSHG creation ratios related to size and harmonophore distributions. Both techniques probe fibril packing order, but the optical scattering probes structures of sizes from about 50-2000 nm where SHG imaging - although only able to resolve individual fibers - builds contrast from the assembly of fibrils. Our findings suggest that type I ovarian tumor structure has the most ordered collagen fibers followed by normal ovary then type II tumors showing the least order.

  14. Ovarian response to gonadotropin treatment initiated relative to wave emergence in ultrasonographically monitored ewes.

    PubMed

    Rubianes, E; Ungerfeld, R; Viñoles, C; Rivero, A; Adams, G P

    1997-06-01

    Follicular recruitment and luteal response to superovulatory treatment initiated relative to the status of the first wave of the ovine estrous cycle (Wave 1) were studied. All ewes (n = 25) received an intravaginal progestagen sponge to synchronize estrous cycles, and ewes were monitored daily by transrectal ultrasonography. Multiple-dose FSH treatment (total dose = 100 mg NIH-FSH-P1) was initiated on the day of ovulation (Day 0 group) in 16 ewes. In the remaining 9 ewes, FSH treatment was started 3 d after emergence of the largest follicle of Wave 1 (Day 3 group). Ewes received PGF(2alpha) with the last 2 FSH treatments to induce luteolysis. Daily blood samples were taken to determine progesterone profiles and to evaluate the luteal response subsequent to superovulation. The ovulation rate was determined by ultrasonography and correlated with direct observation of the ovaries during laparotomy 5 to 6 d after superovulatory estrus when the uterus was flushed to collect embryos. Results confirmed that follicular recruitment was suppressed by the presence of a large, growing follicle. In the Day 0 and Day 3 groups, respectively, mean numbers (+/- SEM) of large follicles (>/= 4 mm) recruited were 6.4 +/- 0.6 and 2.7 +/- 0.7 (P < 0.01) at 48 h after the onset of treatment, and 6.7 +/- 0.5 and 5.1 +/- 0.6 (P = 0.08) at 72 h after the onset of treatment. Ovulation rates were 5.6 +/- 0.8 and 3.3 +/- 0.8 in the respective groups (P < 0.05). The number of transferable embryos was 1.8 +/- 0.5 and 0.3 +/- 0.2 in the respective groups (P < 0.05). Short luteal phases (response in ewes. Response was influenced by the status of the follicular wave. The presence of a large growing follicle

  15. 48 CFR 370.505 - Responsibility determinations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 4 2014-10-01 2014-10-01 false Responsibility determinations. 370.505 Section 370.505 Federal Acquisition Regulations System HEALTH AND HUMAN SERVICES HHS SUPPLEMENTATIONS SPECIAL PROGRAMS AFFECTING ACQUISITION Acquisitions Under the Buy Indian Act...

  16. 48 CFR 370.505 - Responsibility determinations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 4 2013-10-01 2013-10-01 false Responsibility determinations. 370.505 Section 370.505 Federal Acquisition Regulations System HEALTH AND HUMAN SERVICES HHS SUPPLEMENTATIONS SPECIAL PROGRAMS AFFECTING ACQUISITION Acquisitions Under the Buy Indian Act...

  17. 48 CFR 370.505 - Responsibility determinations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Responsibility determinations. 370.505 Section 370.505 Federal Acquisition Regulations System HEALTH AND HUMAN SERVICES HHS SUPPLEMENTATIONS SPECIAL PROGRAMS AFFECTING ACQUISITION Acquisitions Under the Buy Indian Act...

  18. 48 CFR 370.505 - Responsibility determinations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false Responsibility determinations. 370.505 Section 370.505 Federal Acquisition Regulations System HEALTH AND HUMAN SERVICES HHS SUPPLEMENTATIONS SPECIAL PROGRAMS AFFECTING ACQUISITION Acquisitions Under the Buy Indian Act...

  19. 48 CFR 370.505 - Responsibility determinations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 4 2012-10-01 2012-10-01 false Responsibility determinations. 370.505 Section 370.505 Federal Acquisition Regulations System HEALTH AND HUMAN SERVICES HHS SUPPLEMENTATIONS SPECIAL PROGRAMS AFFECTING ACQUISITION Acquisitions Under the Buy Indian Act...

  20. Non-monotonic dose-response effect of bisphenol A on rare minnow Gobiocypris rarus ovarian development.

    PubMed

    Zhang, Yingying; Tao, Shiyu; Yuan, Cong; Liu, Yan; Wang, Zaizhao

    2016-02-01

    Bisphenol A (BPA) is widely spread in the environment, and can cause various reproductive disrupting effects on different organisms, including fish. Our previous published study showed that BPA has non-monotonic (inverted U-shaped) dose-response effect on rare minnow Gobiocypris rarus ovarian weight at different concentrations. To investigate the potential mechanism, we exposed female rare minnow to 1, 15 and 225 µg L(-1) BPA for 7 days in the present study. The levels of vitellogenin (Vtg), sex hormones, hydrogen peroxide (H2O2), glutathione (GSH) and triglyceride (TG) were measured. RNA-seq of ovary tissues was also performed. Result showed that Vtg, sex hormone and TG levels showed an inverted U-shaped increased response, while H2O2 and GSH levels showed a U-shaped inhibited response. RNA-seq data showed that many genes involved in lipid metabolism, oxidative stress, and proteolysis processes were altered. The change of Vtg, H2O2, GSH and TG levels was possibly related to the altered sex hormone levels. Sex hormone's direct effect, Vtg accumulation, TG accumulation and oxidative stress induced proteolysis may contribute to the change of ovary weight.

  1. Development of persistent ovarian follicles during synchronization of estrus influences the superovulatory response to FSH treatment in cattle.

    PubMed

    Wehrman, M E; Fike, K E; Kojima, F N; Bergfeld, E G; Cupp, A S; Mariscal, V; Sanchez, T; Kinder, J E

    1996-02-01

    The synchronization of estrus with synthetic progestins or progesterone (P(4)) results in the development of a large, persistent ovarian follicle. The objectives of the present study were to determine if development of a persistent ovarian follicle during synchronization of estrus suppresses recruitment of additional follicles during FSH treatment. On Day 5 of the estrous cycle (estrus = Day 0), beef cows were treated with 0.5 or 2.0 P(4) releasing intravaginal devices (PRIDs) for 8 d (Experiment 1, n = 20), 5 or 2 d (Experiment 2, n = 44) before initiation of FSH treatment. Prostaglandin F(2alpha) (25 mg) was administered on Days 5 and 6. Superovulation was induced with 24 mg of recombinant bovine FSH (rbFSH, Experiment 1) or 28 mg of FSH-P (Experiment 2) over a 3- or 4-d period, respectively. The PRIDs were removed concurrently with the 5th injection of rbFSH or FSH-P. There was a treatment-by-day interaction (P < 0.001) for the concentration of 17beta-estradiol in cows treated for 8, 5 or 2 d before FSH treatment. In Experiment 1, FSH treatment initiated 8 d after insertion of a 0.5 PRID did not affect the number of CL (6.9 +/- 1.4 vs 6.7 +/- 1.6), ova/embryos (3.7 +/-1.3 vs 3.0 +/- 1.3) and transferable embryos (2.4 +/- 0.9 vs 3.0 +/- 0.9) compared with that of the 2.0 PRIDs. In Experiment 2, FSH treatment initiated 5 d after insertion of a 0.5 PRID decreased the number of CL (4.0 +/- 0.5 vs 8.3 +/- 0.8; P < 0.001), ova/embryos (3.0 +/- 0.6 vs 5.9 +/- 1.2; P < 0.03) and transferable embryos (2.3 +/- 0.6 vs 5.1 +/- 1.0; P < 0.03) compared with that of a 2.0 PRID, respectively. Initiation of FSH treatment 2 d after insertion of a 0.5 PRID compared with a 2.0 PRID had no affect on the number of CL (8.0 +/- 2.1 vs 8.7 +/- 1.2), total ova (4.8 +/- 1.4 vs 6.9 +/- 1.4) and transferable embryos (2.9 +/- 1.2 vs 6.1 +/- 1.7). In conclusion, treatment with low doses of P(4) (0.5 PRID) for 5 d but not for 2 or 8 d before initiation of FSH treatment results in the

  2. High response rates to neoadjuvant platinum-based therapy in ovarian cancer patients carrying germ-line BRCA mutation.

    PubMed

    Gorodnova, Tatiana V; Sokolenko, Anna P; Ivantsov, Alexandr O; Iyevleva, Aglaya G; Suspitsin, Evgeny N; Aleksakhina, Svetlana N; Yanus, Grigory A; Togo, Alexandr V; Maximov, Sergey Ya; Imyanitov, Evgeny N

    2015-12-28

    Preoperative therapy provides an advantage for clinical drug assessment, as it involves yet untreated patients and facilitates access to the post-treatment biological material. Testing for Slavic founder BRCA mutations was performed for 225 ovarian cancer (OC) patients, who were treated by platinum-based neoadjuvant therapy. 34 BRCA1 and 1 BRCA2 mutation carriers were identified. Complete clinical response was documented in 12/35 (34%) mutation carriers and 8/190 (4%) non-carriers (P = 0.000002). Histopathologic response was observed in 16/35 (46%) women with the germ-line mutation versus 42/169 (25%) patients with the wild-type genotype (P = 0.02). Somatic loss of heterozygosity (LOH) for the remaining wild-type BRCA1 allele was detected only in 7/24 (29%) post-neoadjuvant therapy residual tumor tissues as compared to 9/11 (82%) BRCA1-associated OC, which were not exposed to systemic treatment before the surgery (P = 0.009). Furthermore, comparison of pre- and post-treatment tumor material obtained from the same patients revealed restoration of BRCA1 heterozygosity in 2 out of 3 sample pairs presenting with LOH at diagnosis. The obtained data confirm high sensitivity of BRCA-driven OC to platinating agents and provide evidence for a rapid selection of tumor cell clones without LOH during the course of therapy.

  3. Plasma concentrations of PGFM and uterine and ovarian responses in early lactation dairy cows fed omega-3 and omega-6 fatty acids.

    PubMed

    Dirandeh, E; Towhidi, A; Pirsaraei, Z Ansari; Hashemi, F Adib; Ganjkhanlou, M; Zeinoaldini, S; Roodbari, A Rezaei; Saberifar, T; Petit, H V

    2013-07-15

    A total of 120 dairy cows were assigned randomly to three diets to determine the effects of omega-6 or omega-3 fatty acid (FA) supplementation on uterine diseases, ovarian responses, and blood concentrations of estradiol, progesterone, and PGFM in lactating Holstein dairy cows. Diets contained either protected palm oil (C), extruded linseed (L), or roasted whole soybeans (S), and they were fed from calving to Day 70 postpartum. Estrous cycles were synchronized and ovarian follicular development was monitored daily for an entire cycle. There were no differences among diets in the incidence of lameness, mastitis, or metritis, but the incidence of clinical endometritis was lower (P < 0.05) in cows fed S (0%) compared with cows fed C (28.2%) and L (20.5%). Uterine involution in cows fed S occurred 3.77 and 2.78 days earlier, respectively, than in those fed C and L. The PGFM response 60 minutes after an oxytocin challenge was highest for cows fed S and lowest for cows fed L. Mean plasma progesterone concentration on Day 15 of the synchronized cycle was higher in cows fed S (14.5 ng/mL) and L (15.0 ng/mL) than in those fed C (12.0 ng/mL). The ovulatory follicle on Day 21 of the estrous cycle (estrous = Day 0) was larger in cows fed S (16.1 ± 0.9 mm) and L (15.7 ± 0.7 mm) compared with cows fed C (13.2 ± 0.87 mm; P = 0.02) but there were no significant differences between cows fed diets S and L. The mean number of small and medium follicles and diameter of subordinate follicle were similar among diets. In conclusion, feeding a source of omega-6 FA can be a strategy to improve uterine health after calving, although a source of omega-3 FA such as L should be fed after uterine involution to decrease PGF2α secretion.

  4. Evaluation of DNA Repair Function as a Predictor of Response in a Clinical Trial of PARP Inhibitor Monotherapy for Recurrent Ovarian Carcinoma

    DTIC Science & Technology

    2015-10-01

    estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the...data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this...unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT This document provides an annual progress report for the grant W81XWH-13-1-0485 entitled “Ovarian Cancer

  5. Validation of Electrochemiluminiscence Immunoassay for Ovarian Steroid Determination in Rhinella arenarum.

    PubMed

    Arias Torres, Ana Josefina; Páez, José Bernardino; Zelarayán, Liliana Isabel

    2016-04-01

    In this work, we describe the validation of an electrochemiluminescence immunoassay (ECLIA) that allowed us for the first time to determine the levels of progesterone (P4 ) and testosterone (T) secreted by Rhinella arenarum follicles during the preovulatory (POP) and reproductive (RP) periods. We also verified the relation between P4 and T levels and oocyte maturation. Moreover, we demonstrated that the extraction protocol developed for the determinations of P4 and T by ECLIA proved to be efficient and reproducible since the efficacy of the extraction was above 95% in all assays conducted. The results indicate that in the validation process the variation coefficient (CV) between assays is compatible with the analytical procedures based on automated immunoassays (CV < 8%) and that the adaptation proposed for the samples allows the determination of T and P4 with the Cobas e-411 analyzer. Our results indicate that in basal conditions the levels of T released by R. arenarum follicles were higher than those of P4 during POP and RP. In these conditions, steroid secretion failed to induce germinal vesicle break down (GVBD) in the follicles. Under gonadotropin stimulation, steroidogenesis showed a remarkable increase in both periods, especially during POP. This increase was correlated with a high maturation percentage in the follicles incubated in vitro (GVBD = 72 ± 16%) during POP. During RP, human Chorionic Gonadotropin (hCG) induced 81.75 ± 9.1% GVBD. This study is the first report of the seasonal steroidogenic activity in the ovary of R. arenarum in situ using an ECLIA-modified protocol developed in our laboratory.

  6. Oncolytic virotherapy for ovarian cancer.

    PubMed

    Li, Shoudong; Tong, Jessica; Rahman, Masmudur M; Shepherd, Trevor G; McFadden, Grant

    2012-08-01

    In the past two decades, more than 20 viruses with selective tropism for tumor cells have been developed as oncolytic viruses (OVs) for treatments of a variety of malignancies. Of these viruses, eleven have been tested in human ovarian cancer models in preclinical studies. So far, nine phase I or II clinical trials have been conducted or initiated using four different types of OVs in patients with recurrent ovarian cancers. In this article, we summarize the different OVs that are being assessed as therapeutics for ovarian cancer. We also present an overview of recent advances in identification of key genetic or immune-response pathways involved in tumorigenesis of ovarian cancer, which provides a better understanding of the tumor specificities and oncolytic properties of OVs. In addition, we discuss how next-generation OVs could be genetically modified or integrated into multimodality regimens to improve clinical outcomes based on recent advances in ovarian cancer biology.

  7. Oncolytic virotherapy for ovarian cancer

    PubMed Central

    Li, Shoudong; Tong, Jessica; Rahman, Masmudur M; Shepherd, Trevor G; McFadden, Grant

    2012-01-01

    In the past two decades, more than 20 viruses with selective tropism for tumor cells have been developed as oncolytic viruses (OVs) for treatments of a variety of malignancies. Of these viruses, eleven have been tested in human ovarian cancer models in preclinical studies. So far, nine phase I or II clinical trials have been conducted or initiated using four different types of OVs in patients with recurrent ovarian cancers. In this article, we summarize the different OVs that are being assessed as therapeutics for ovarian cancer. We also present an overview of recent advances in identification of key genetic or immune-response pathways involved in tumorigenesis of ovarian cancer, which provides a better understanding of the tumor specificities and oncolytic properties of OVs. In addition, we discuss how next-generation OVs could be genetically modified or integrated into multimodality regimens to improve clinical outcomes based on recent advances in ovarian cancer biology. PMID:25977900

  8. Role of ghrelin in regulating rabbit ovarian function and the response to LH and IGF-I.

    PubMed

    Sirotkin, Alexander V; Rafay, Ján; Kotwica, Ján; Darlak, Krzysztof; Valenzuela, Francisco

    2009-04-01

    The aim of these in vivo and in vitro studies was to examine the role of ghrelin in the control of plasma hormone concentrations, the proliferation, apoptosis and secretory activity of ovarian granulosa cells and the response of these cells to hormonal treatments. Female rabbits were injected with ghrelin (10 microg/animal/day for one week before ovulation induced by 25IU PMSG and 0.25IU LHRH). On the day of ovulation, blood samples were collected and analyzed for concentrations of progesterone (P(4)), testosterone (T), estradiol (E(2)), estrone-sulphate (ES), insulin-like growth factor I (IGF-I) and leptin (L) by RIA. Some control and ghrelin-treated animals were killed in the periovulatory period, their ovaries were weighed and granulosa cells were isolated and cultured for 2d. Cell proliferation (expression of PCNA) and apoptosis (expression of TdT) were evaluated by immunocytochemistry and TUNEL respectively. Secretion of P(4), T, E(2), IGF-I, and prostaglandin F (PGF) by granulosa cells cultured with and without LH or IGF-I (1, 10 or 100 ng/ml medium) was assessed by RIA. The remaining control and treated animals were kept until parturition, while the number, viability and body weight of pups were recorded. Ghrelin treatment increased rabbit plasma T and decreased ES concentrations but did not influence P(4), E(2), IGF-I or L. Granulosa cells from ghrelin-treated animals showed higher expression of PCNA and lower expression of TdT, than those from control animals. They also secreted less P(4), T, E(2), IGF-I and PGF than granulosa cells from untreated animals. Treatment of cultured granulosa cells with ghrelin (1, 10 or 100 ng/ml medium) either increased (at 1 ng/ml) or decreased (at 10 ng/ml) P(4) secretion, increased (at 100 ng/ml) or decreased (at 10 ng/ml) IGF-I secretion, decreased T (at 1 and 10 ng/ml) and OT (at 1 ng/ml) secretion, and increased (at 100 ng/ml) PGF secretion. LH treatment of cells from control animals stimulated P(4) (at 1 and 10 ng

  9. Differential cellular responses induced by dorsomorphin and LDN-193189 in chemotherapy-sensitive and chemotherapy-resistant human epithelial ovarian cancer cells.

    PubMed

    Ali, Jennifer L; Lagasse, Brittany J; Minuk, Ainsley J; Love, Allison J; Moraya, Amani I; Lam, Linda; Arthur, Gilbert; Gibson, Spencer B; Morrison, Ludivine Coudière; Werbowetski-Ogilvie, Tamra E; Fu, Yangxin; Nachtigal, Mark W

    2015-03-01

    Inherent or acquired drug resistance is a major contributor to epithelial ovarian cancer (EOC) mortality. Novel drugs or drug combinations that produce EOC cell death or resensitize drug resistant cells to standard chemotherapy may improve patient treatment. After conducting drug tolerability studies for the multikinase inhibitors dorsomorphin (DM) and it is structural analogue LDN-193189 (LDN), these drugs were tested in a mouse intraperitoneal xenograft model of EOC. DM significantly increased survival, whereas LDN showed a trend toward increased survival. In vitro experiments using cisplatin (CP)-resistant EOC cell lines, A2780-cp or SKOV3, we determined that pretreatment or cotreatment with DM or LDN resensitized cells to the killing effect of CP or carboplatin (CB). DM was capable of blocking EOC cell cycle and migration, whereas LDN produced a less pronounced effect on cell cycle and no effect on migration. Subsequent analyses using primary human EOC cell samples or additional established EOC cells lines showed that DM or LDN induced a dose-dependent autophagic or cell death response, respectively. DM induced a characteristic morphological change with the appearance of numerous LC3B-containing acidic vacuoles and an increase in LC3BII levels. This was coincident with a decrease in cell growth and the altered cell cycle consistent with DM-induced cytostasis. By contrast, LDN produced a caspase 3-independent, reactive oxygen species-dependent cell death. Overall, DM and LDN possess drug characteristics suitable for adjuvant agents used to treat chemotherapy-sensitive and -resistant EOC.

  10. Ovarian cysts

    MedlinePlus

    ... cysts due to hormone-related conditions such as polycystic ovary syndrome . Symptoms Ovarian cysts often cause no symptoms. An ... You may need other treatments if you have polycystic ovary syndrome or another disorder that can cause cysts. Outlook ( ...

  11. Ovarian Cancer

    MedlinePlus

    ... and getting enough rest can help combat the stress and fatigue of cancer. There's no sure way to prevent ovarian cancer. But certain factors are associated with lower risk: Use of oral contraceptives, especially for more than 10 years Previous ...

  12. Ovarian hypofunction

    MedlinePlus

    ... may be caused by genetic factors such as chromosome abnormalities. It may also occur with certain autoimmune disorders that disrupt the normal function of the ovaries. Chemotherapy and radiation therapy can also cause ovarian hypofunction.

  13. Ovarian Cysts

    MedlinePlus

    ... information Endometriosis fact sheet Ovarian cancer fact sheet Polycystic ovary syndrome fact sheet The javascript used in this widget ... ovaries make many small cysts. This is called polycystic ovary syndrome (PCOS). PCOS can cause problems with the ovaries ...

  14. Relationship between the ovarian follicular response at the start of an Ovsynch-TAI program and pregnancy outcome in the Mediterranean river buffalo.

    PubMed

    Neglia, Gianluca; Gasparrini, Bianca; Salzano, Angela; Vecchio, Domenico; De Carlo, Esterina; Cimmino, Roberta; Balestrieri, Anna; D'Occhio, Michael J; Campanile, Giuseppe

    2016-12-01

    The aim of this study was to evaluate the relationship between the ovarian follicular response at the start of the OVsynch-fixed-time artificial insemination (TAI) program and pregnancy outcome in the Mediterranean river buffalo. The study involved 116 pluriparous buffaloes at 118 ± 65 days in milk maintained under commercial conditions on a buffalo dairy enterprise in southern Italy. Synchronization of the stage of the estrous cycle in the Ovsynch-TAI program involves an injection of GnRH on Day 0 (GnRH1), PGF2α on Day 7, and GnRH on Day 9 (GnRH2). Timed artificial insemination is carried out on Day 10. Ovarian ultrasound examinations were undertaken on days 0, 2, 7, 9, 10, and 11 to record total follicles, the dimensions of follicles greater than 0.75 cm, dimensions of the corpus luteum (CL), and the occurrence of ovulation. Blood concentrations of P4 were measured on days 0 and 10 and 10 days after TAI. Pregnancy status was determined on days 27 and 45 after TAI to calculate late embryonic mortality. The data were analyzed by ANOVA and multiple logistic regression. A total of 70 of 116 (60.4%) buffaloes showed ovulation after GnRH1. Buffaloes that ovulated after GnRH1 had a smaller (P < 0.05) area of the ovulatory follicle on Day 0 compared with buffaloes that did not ovulate (1.08 ± 0.1 and 1.29 ± 0.1 cm(2), respectively). The former buffaloes also had a larger (P < 0.05) CL area (1.81 ± 0.1 and 1.51 ± 0.1 cm(2), respectively) and greater (P < 0.05) blood concentrations of P4 (1.84 ± 0.2 and 1.34 ± 0.2 ng/mL, respectively) on Day 0. A larger (P < 0.05) proportion of buffaloes that ovulated after GnRH1 showed regression of the CL after the injection of PGF2α on Day 7 compared with buffaloes that did not ovulate (68 of 69 [98.6%] and 27 of 32 [84.4%], respectively). Buffaloes that ovulated after GnRH1 also had a greater (P < 0.05) ovulation rate after GnRH2 than buffaloes that did not ovulate (65 of 70 [92.8%] and 37 of 46

  15. Death by bleomycin pulmonary toxicity in ovarian dysgerminoma with pathologic complete response to chemotherapy. A case report.

    PubMed

    Calzas Rodríguez, Julia; Carmen Juarez Morales, María Del; Casero, Miguel Angel Racionero

    2016-01-01

    With cisplatin-based chemotherapy, most patients with ovarian dysgerminoma will survive long-term. Bleomycin is an important part of ovarian germ cell tumors (OGCT) treatment, and its dose-limiting toxicity is the development of pulmonary toxicity and it is increased in patients older than 40 years. We report the case of an elderly patient with an unresectable ovarian dysgerminoma who received neoadjuvant chemotherapy and who developed fatal bleomycin pulmonary toxicity (BPT) after surgery. A monitoring of pulmonary function is not routinely recommended for detecting BPT, although together with carefully assessment for symptoms or signs suggestive of pulmonary toxicity is the best way to reduce the risk of BPT. The frequency of pulmonary events in older patients makes us to think about the possibility of either reduce the dose of bleomycin or removing it from the BEP in ovarian GCT.

  16. Steroid Signaling and Temperature-Dependent Sex Determination – Reviewing the Evidence for Early Action of Estrogen during Ovarian Determination in the Red-Eared Slider Turtle (Trachemys scripta elegans)

    PubMed Central

    Ramsey, Mary; Crews, David

    2009-01-01

    The developmental processes underlying gonadal differentiation are conserved across vertebrates, but the triggers initiating these trajectories are extremely variable. The red-eared slider turtle (Trachemys scripta elegans) exhibits temperature-dependent sex determination (TSD), a system where incubation temperature during a temperature-sensitive period of development determines offspring sex. However, gonadal sex is sensitive to both temperature and hormones during this period – particularly estrogen. We present a model for temperature-based differences in aromatase expression as a critical step in ovarian determination. Localized estrogen production facilitates ovarian development while inhibiting male-specific gene expression. At male-producing temperatures aromatase is not upregulated, thereby allowing testis development. PMID:18992835

  17. Methamphetamine and Ovarian Steroid Responsive Cells in the Posteriodorsal Medial Amygdala are Required for Methamphetamine-enhanced Proceptive Behaviors

    PubMed Central

    Williams, Katrina M.; Mong, Jessica A.

    2017-01-01

    Methamphetamine (Meth) is a psychomotor stimulant strongly associated with increases in sexual drive and impulse in both men and women. These changes in sexual motivation have a greater impact on women due to their likelihood of facing the greater burden of unplanned pregnancies, as well as increased risk for psychiatric co-morbidities such as depression. We have previously established a rodent model of Meth-induced increases in sexual motivation. Using this model, we have identified the posteriodorsal medial amygdala (MePD) via excitotoxic lesion studies as a necessary nucleus in Meth-facilitated female sexual motivation. While lesion studies give us insight into key nuclei that may be targets of Meth action, such an approach does not give insight into the identity of the specific MePD neurons or neural circuitry involved in Meth-induced increases in proceptive behaviors. Using the DAUN02 inactivation method, a recently established technique for removing behaviorally relevant cell populations, we present evidence that the ovarian steroid/Meth responsive cells in the MePD are necessary for Meth-induced facilitation of proceptive behaviors. These findings form the basis for future work that will allow for the classification of neuronal subtypes involved in the MePD’s modulation of proceptive behavior as well as a stronger understanding of the neurocircuitry of female sexual motivation. PMID:28045134

  18. The role of interleukin-8 (IL-8) and IL-8 receptors in platinum response in high grade serous ovarian carcinoma.

    PubMed

    Stronach, Euan A; Cunnea, Paula; Turner, Christina; Guney, Tankut; Aiyappa, Radhika; Jeyapalan, Senthuran; de Sousa, Camila H; Browne, Alacoque; Magdy, Nesreen; Studd, James B; Sriraksa, Ruethairat; Gabra, Hani; El-Bahrawy, Mona

    2015-10-13

    Platinum based drugs are the cornerstone of chemotherapy for ovarian cancer, however the development of chemoresistance hinders its success. IL-8 is involved in regulating several pro-survival pathways in cancer. We studied the expression of IL-8 and IL-8 receptors in platinum sensitive and resistant cell lines. Using qRT-PCR and immunohistochemistry, both platinum sensitive (PEA1, PEO14) and resistant (PEA2, PEO23) show increased expression of IL-8 and IL-8 receptors. IL-8RA shows nuclear and cytoplasmic expression, whilst IL-8RB is present solely in the cytoplasm. Knockdown of IL-8 increased sensitivity to cisplatin in platinum sensitive and reversed platinum resistance in resistant cell lines, decreased the expression of anti-apoptotic Bcl-2 and decreased inhibitory phosphorylation of pro-apoptotic Bad. IL-8 receptor antagonist treatment also enhanced platinum sensitivity. Nuclear localisation of IL-8RA was only detected in platinum resistant tumours. Inhibition of IL-8 signalling can enhance response in platinum sensitive and resistant disease. Nuclear IL-8RA may have potential as a biomarker of resistant disease.

  19. The role of interleukin-8 (IL-8) and IL-8 receptors in platinum response in high grade serous ovarian carcinoma

    PubMed Central

    Stronach, Euan A.; Cunnea, Paula; Turner, Christina; Guney, Tankut; Aiyappa, Radhika; Jeyapalan, Senthuran; de Sousa, Camila H.; Browne, Alacoque; Magdy, Nesreen; Studd, James B.; Sriraksa, Ruethairat; Gabra, Hani; El-Bahrawy, Mona

    2015-01-01

    Platinum based drugs are the cornerstone of chemotherapy for ovarian cancer, however the development of chemoresistance hinders its success. IL-8 is involved in regulating several pro-survival pathways in cancer. We studied the expression of IL-8 and IL-8 receptors in platinum sensitive and resistant cell lines. Using qRT-PCR and immunohistochemistry, both platinum sensitive (PEA1, PEO14) and resistant (PEA2, PEO23) show increased expression of IL-8 and IL-8 receptors. IL-8RA shows nuclear and cytoplasmic expression, whilst IL-8RB is present solely in the cytoplasm. Knockdown of IL-8 increased sensitivity to cisplatin in platinum sensitive and reversed platinum resistance in resistant cell lines, decreased the expression of anti-apoptotic Bcl-2 and decreased inhibitory phosphorylation of pro-apoptotic Bad. IL-8 receptor antagonist treatment also enhanced platinum sensitivity. Nuclear localisation of IL-8RA was only detected in platinum resistant tumours. Inhibition of IL-8 signalling can enhance response in platinum sensitive and resistant disease. Nuclear IL-8RA may have potential as a biomarker of resistant disease. PMID:26267317

  20. Evaluation of results obtained with corifollitropin alfa after poor ovarian response in previous cycle using recombinant follicular stimulating hormone in the long-term protocol

    PubMed Central

    Salgueiro, Lister L.; Rolim, Juliana R.; Moura, Bernardo R. L.; Machado, Suelen P. P.; Haddad, Carolina

    2016-01-01

    Objective This study evaluated the use of Corifollitropin alfa in patients with previous poor response to recombinant follicle stimulating hormone in long-term protocols using gonadotropin-releasing hormone. Methods Twenty-seven poor responders to previous treatment with the long term protocol using the recombinant follicle stimulating hormone (Group 1) were selected and then submitted to a second attempt using the same long term protocol with Corifollitropin alfa instead of the recombinant follicle stimulating hormone (Group 2). Ovarian down-regulation was achieved using subcutaneous administration of Leuprolide Acetate. Ovarian stimulation was performed with recombinant follicle stimulating hormone until the administration of human chorionic gonadotropin, followed by follicular aspiration (Group 1). Group 2 was submitted to this same protocol using Corifollitropin alfa instead of recombinant follicle stimulating hormone. Results There were significant differences in the number of aspirated oocytes, percentage of mature oocytes, amount of injected oocytes and transferred embryos - with all of these parameters being increased in the Corifollitropin alfa group. In addition, the rates of pregnancy and ongoing pregnancy were also significantly higher in the Corifollitropin alfa group. Conclusion The present study demonstrated that the use of Corifollitropin alfa in the long-term protocol could be a highly effective alternative for patients with poor ovarian response, who were unsuccessful in a previous treatment with In Vitro Fertilization - Intracytoplasmic Sperm Injection. PMID:27584604

  1. Predictive values of anti-müllerian hormone, antral follicle count and ovarian response prediction index (ORPI) for assisted reproductive technology outcomes.

    PubMed

    Ashrafi, Mahnaz; Hemat, Mandana; Arabipoor, Arezoo; Salman Yazdi, Reza; Bahman-Abadi, Akram; Cheraghi, Rezvaneh

    2017-01-01

    This prospective study was performed from June 2012 to June 2014 at Royan Institute to compare the predictive values of serum anti-müllerian hormone (AMH), antral follicle count (AFC) and ovarian response prediction index (ORPI) ([AFC × AMH]/age) for in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) cycle outcomes. Five hundred and fifty women included in the study with male factor and unexplained infertility were the first candidates for IVF/ICSI cycles. Serum AMH level was measured by a commercial ELISA kit and AFC was calculated by a transvaginal ultrasonography on day 2-3 of the menstrual cycle before starting ovarian stimulation. All women underwent IVF/ICSI cycles using a long standard protocol with gonadotropin-releasing hormone agonist. The receiver operating characteristic curves (ROC) analysis showed that both AMH and AFC were good predictors of ovarian response with an area under the curves (AUC) > 0.75; even it seems that AFC was being a better predictor. Combining these variables is necessary as ORPI will not improve the prediction value. All the variables had poor predictive ability (AUC <0.60) for clinical pregnancy and live birth rates. Logistic regression analysis showed the AMH less than 0.4 ng/ml and quality of transferred embryos were significant predictors for clinical pregnancy rate.

  2. The pattern of LH secretion and the ovarian response to the 'ram effect' in the anoestrous ewe is influenced by body condition but not by short-term nutritional supplementation.

    PubMed

    Scaramuzzi, R J; Oujagir, L; Menassol, J-B; Freret, S; Piezel, A; Brown, H M; Cognié, J; Fabre Nys, C

    2014-10-01

    In sheep, the 'ram effect' induces out-of-season fertility and good nutrition increases prolificacy. This experiment determined if fatness or short-term nutritional supplementation modified the response to the 'ram effect'. A group of 48 Île-de-France ewes were fed diets that produced groups with body-condition scores (BCS) of >3.0 and <2.0. Within each BCS group animals were supplemented daily with 500g of lupins from Day -5 to Day 0 (ram introduction) resulting in four groups: low BCS, supplemented (n=7) and non-supplemented (n=8) and high BCS, supplemented (n=12) and non-supplemented (n=11). The blood concentrations of glucose and insulin and the LH response to gonadotrophin-releasing hormone (GnRH) were determined. After the 'ram effect' the pattern of LH pulsatility, the LH surge and ovarian responses were analysed. Low BCS ewes had lower glucose and insulin (P<0.001) and supplementation increased both (P≤0.001). The increase in LH induced by GnRH was reduced in low BCS ewes (P=0.015) but it was not affected by supplementation. Similarly, LH pulsatility was reduced in low BCS ewes (P<0.05). The LH surge and ovarian cyclicity were not affected but the follow-up cycle was delayed (P=0.034) and progesterone was reduced (P=0.029) in low BCS ewes. There was an effect of BCS on ovulation rate (P<0.05). These results show that the BCS can modify the response to the 'ram effect' and that supplementation has little effect on this response.

  3. Neoadjuvant Chemotherapy of Ovarian Cancer Results in Three Patterns of Tumor-Infiltrating Lymphocyte Response with Distinct Implications for Immunotherapy.

    PubMed

    Lo, Charlotte S; Sanii, Sanaz; Kroeger, David R; Milne, Katy; Talhouk, Aline; Chiu, Derek S; Rahimi, Kurosh; Shaw, Patricia A; Clarke, Blaise A; Nelson, Brad H

    2017-02-15

    Purpose: Some forms of chemotherapy can enhance antitumor immunity through immunogenic cell death, resulting in increased T-cell activation and tumor infiltration. Such effects could potentially sensitize tumors to immunotherapies, including checkpoint blockade. We investigated whether platinum- and taxane-based chemotherapy for ovarian cancer induces immunologic changes consistent with this possibility.Experimental Design: Matched pre- and post-neoadjuvant chemotherapy tumor samples from 26 high-grade serous carcinoma (HGSC) patients were analyzed by immunohistochemistry (IHC) for a large panel of immune cells and associated factors. The prognostic significance of post-chemotherapy TIL patterns was assessed in an expanded cohort (n = 90).Results: Neoadjuvant chemotherapy was associated with increased densities of CD3(+), CD8(+), CD8(+) TIA-1(+), PD-1(+) and CD20(+) TIL. Other immune subsets and factors were unchanged, including CD79a(+) CD138(+) plasma cells, CD68(+) macrophages, and MHC class I on tumor cells. Immunosuppressive cell types were also unchanged, including FoxP3(+) PD-1(+) cells (putative regulatory T cells), IDO-1(+) cells, and PD-L1(+) cells (both macrophages and tumor cells). Hierarchical clustering revealed three response patterns: (i) TIL(high) tumors showed increases in multiple immune markers after chemotherapy; (ii) TIL(low) tumors underwent similar increases, achieving patterns indistinguishable from the first group; and (iii) TIL(negative) cases generally remained negative. Despite the dramatic increases seen in the first two patterns, post-chemotherapy TIL showed limited prognostic significance.Conclusions: Chemotherapy augments pre-existing TIL responses but fails to relieve major immune-suppressive mechanisms or confer significant prognostic benefit. Our findings provide rationale for multipronged approaches to immunotherapy tailored to the baseline features of the tumor microenvironment. Clin Cancer Res; 23(4); 925-34. ©2016 AACR.

  4. [Ovarian carcinoma antigen (CA 125) and ovarian cancer (clinical follow-up and prognostic studies)].

    PubMed

    Göcze, P; Vahrson, H

    1993-04-25

    Serum concentrations of ovarian carcinoma antigen (CA 125) were determined by Abbot CA 125-EIA Monoclonal kit from 66 patients with malignant ovarian tumor. The preoperative serum levels of CA 125 were elevated (> 35.0 IU/ml) in 93% (27/29). After the laparotomy and before the irradiation or chemotherapy in 36% (24/36) of patients had elevated levels. No significant correlation was seen between elevated levels and histology, tumor grade and clinical stage. However, the rate of positive cases were significantly higher in advanced stages than in the 1st stage (p < 0.05). No significant correlation was found between the preoperative levels of CA 125 and the clinical course. The postoperative elevated levels indicated bad prognosis. Good conformity was found between CA 125 levels and the therapy response. Serological follow up revealed a correlation with the clinical course of ovarian carcinoma in 84% (44/52). In patients with tumor progression the CA 125 levels increased before clinical signs of progression with median lead time of 97 days. The second look laparotomy proved, that residual tumor larger than 2 cm of diameter cause elevated levels. Smaller tumors remained marker negatives. CA 125 determination before operation, during and after therapy provide a useful tool in detecting progression and persistence of ovarian carcinoma.

  5. What Determines the Response: Test or Reference?

    NASA Technical Reports Server (NTRS)

    Chukova, S. V.; Ahumada, A. J., Jr.; Null, Cynthia (Technical Monitor)

    1998-01-01

    The stability of sensory memory has been studied by presenting a reference stimulus, a delay, and a test stimulus. As has been pointed out by Lages and Treisman (1998 Vision Research 38 557-572), the usual measure of performance depends only on the effect of test variations on the responses. The Weber fraction characterizing performance is more properly called the test stimulus Weber fraction. We measure the relative contribution of the test and reference to the response by the ratio of the test Weber fraction to the reference Weber fraction. The stimuli were two dark lines on a bright background. Seven reference separations, varying from 9.5 to 16.7 arc min, were intermixed in each run. Interstimulus intervals (ISI) of 50, 200 and 2000 msec and intertrial intervals (ITI) of 500 and 2500 msec were investigated. When the ISI was short (50 or 200 msec), for both ITIs, responses were determined equally by the test and reference. For the long ISI (2000 msec), the reference stimulus contributed less. However, only for the 500 msec ITI (and not for all observers) was the contribution of the reference stimulus negligible, as Treisman's criterion setting theory might suggest.

  6. The postpartum period in dromedary camels: uterine involution, ovarian activity, hormonal changes, and response to GnRH treatment.

    PubMed

    Derar, R; Ali, A; Al-Sobayil, F A

    2014-12-30

    The aim of the present study was to investigate the time for complete uterine involution and resumption of ovarian activity in postpartum dromedary camels, relative to hormonal changes. A total of six females were examined by ultrasonography twice weekly starting 3d after parturition. GnRH was administered when the follicles reached ≥0.9cm diameter. Blood samples were collected for hormonal analysis. Results revealed that the mean intervals for complete involution of the previously gravid horn, non-gravid horn, and cervix were 34.33±3.9, 29.01±0.81, and 28.71±1.51d, respectively. After GnRH treatment (Days 17-34), five of the six camels had ovulated. The corpus luteum was detected by Day 4.1±1.6 after GnRH treatment and lasted for 6±1.1d. Serum progesterone (P4) was basal and increased only after GnRH treatment. Serum estradiol 17-β (E2) peaked twice: when a large follicle was detected and 8.5±2.8d post-GnRH treatment. The serum FSH pattern was biphasic, with two peaks just before the recruitment of small follicles and 4.67±4.1d after GnRH treatment. The five ovulating females were mated; two conceived after the first service and three after the second service. The interval from calving to conception was 78.16±3.71d. It was concluded that in dromedary camels, involution of the uterus is completed by the 5th week postpartum, these camels are highly responsive to early GnRH treatment, and they can be mated between the 5th and 6th week after parturition with encouraging conception rates.

  7. Human anti-murine antibody responses in ovarian cancer patients undergoing radioimmunotherapy with the murine monoclonal antibody OC-125

    SciTech Connect

    Muto, M.G.; Finkler, N.J.; Kassis, A.I.; Lepisto, E.M.; Knapp, R.C. )

    1990-08-01

    Human anti-murine antibody (HAMA) responses were monitored in 23 patients with recurrent or persistent epithelial ovarian carcinoma undergoing single-dose intraperitoneal radioimmunotherapy (RIT) with the murine monoclonal antibody OC-125. Sera of patients receiving escalating doses of OC-125 F(ab')2 (10-70 mg) radiolabeled with 18 to 141 mCi of iodine-131 were assayed for HAMA by a protein A-based radioimmunoassay. Overall, 70% of patients (16/23) developed HAMA within 10 to 46 days (median = 29) postinfusion, with peak values (23 +/- 6 to 325 +/- 10 micrograms/ml) at 32 to 102 days (median = 38). HAMA was undetectable prior to infusion in all cases and persisted up to 76 weeks. Of patients receiving a dose of 123 mCi or less, 80% (16/20) developed HAMA, whereas in the 140-mCi group, none of the three patients had detectable levels. Two patients in the 140-mCi group demonstrated dose-limiting bone marrow toxicity (severe thrombocytopenia and neutropenia). It is concluded that a single intraperitoneal dose of monoclonal antibody leads to a high incidence of HAMA production. The results also suggest that the likelihood of HAMA formation in patients who either had undergone recent chemotherapy or had received the highest dose of the radioimmunoconjugate is reduced. These observations may be of significance in designing multiple-dose therapy trials as HAMA has been demonstrated to decrease antibody-to-tumor binding and may potentially increase renal, hepatic, and hematologic toxicity associated with radioimmunotherapy.

  8. Granulosa cell responsiveness to follicle stimulating hormone during early growth of hen ovarian follicles.

    PubMed

    Johnson, A L; Lee, Jeeyoung

    2016-01-01

    In the laying hen ovary, the cyclic recruitment of a follicle represents a process in which a single follicle is selected to enter the rapid growth phase and undergo final maturation prior to ovulation. Published data support the proposal that final differentiation of the granulosa cell (GC) layer commences at the time of follicle selection. This process is characterized by the enhanced capacity for FSH-induced cell signaling via the protein kinase A/cyclic adenosine monophosphate (cAMP) pathway. One consequence of such signaling within the GC layer is the initial capacity for steroidogenesis (predominantly progesterone production) mediated by increased expression of mRNA encoding steroidogenic acute regulatory protein (STAR) and the cholesterol side-chain cleavage enzyme (CYP11A). Prior to selection, the GC layer remains minimally responsive to a 3 h challenge with FSH (10 ng/mL), in vitro, compared to that from the most recently selected 9- to 12-mm follicle. By comparison, when the duration of the cell culture prior to FSH challenge is increased to 18 h, GCs collected from 1- to 2-mm, 3- to 5-mm, and 6- to 8-mm follicles respond to a 3 h FSH challenge by increasing STAR expression and progesterone production, with the greatest response from GCs collected from 6- to 8-mm follicles. Culture with Bone Morphogenetic Protein 6 (BMP6) enhances both CYP11A expression and FSH responsiveness at each stage of development, with the greatest response again occurring in GCs from 6- to 8-mm follicles. Significantly, factors that activate mitogen activated protein kinase (MAPK) or protein kinase C (PKC) signaling prevent the ability of prolonged culture or culture with BMP6 to induce FSH-responsiveness and the initiation of GC differentiation at each stage of development. Collectively, these results provide further support for the hypothesis that prior to follicle selection, inhibitory cell signaling (e.g., MAPK, PKC) maintains the GC layer in an undifferentiated state in

  9. Ovarian responses of dairy buffalo cows to timed artificial insemination protocol, using new or used progesterone devices, during the breeding season (autumn-winter).

    PubMed

    Monteiro, Bruno Moura; de Souza, Diego Cavalcante; Vasconcellos, Guilherme Souza Floriano Machado; Corrêa, Thalita Bueno; Vecchio, Domenico; de Sá Filho, Manoel Francisco; de Carvalho, Nelcio Antonio Tonizza; Baruselli, Pietro Sampaio

    2016-01-01

    This study evaluated the effect of new or used P4 devices on the ovarian responses of dairy buffalo that were administered an estradiol (E2) plus progesterone (P4)-based timed artificial insemination (TAI) protocol during the breeding season. On the first day of the TAI protocol, 142 cows were randomly assigned to receive one of the following: a new device (New; 1.0 g of P4; n = 48); a device that had previously been used for 9 days (Used1x, n = 47); or a device that had previously been used for 18 days (Used2x, n = 47). Ultrasound was used to evaluate the following: the presence of a corpus luteum (CL); the diameter of the dominant follicle (ØDF) during protocol; ovulatory response; and pregnancies per AI (P/AI). Despite similar responses among the treatments, there was a significant positive association of the ØDF during TAI protocol with ovulatory responses and number of pregnancies. In conclusion, satisfactory ovarian responses and a satisfactory pregnancy rate were achieved when grazing dairy buffalo were subjected to the TAI protocol in breeding season, independent of whether a new or used P4 device was used. Furthermore, the presence of the larger follicle was associated with a higher ovulation rate and higher P/AI following TAI.

  10. MRI in predicting the response of ovarian endometriomas to hormone therapy

    SciTech Connect

    Sugimura, Kazuro; Okizuka, Hiromi; Kaji, Yasushi

    1996-01-01

    Our goal was to investigate the usefulness of MRI in predicting the response of endometriomas to hormone therapy. MRI and laparoscopy at the onset of treatment and follow-up MRI after 6 months of hormone therapy were performed in 21 patients with 49 endometriomas. T1- and T2-weighted images were obtained with a 1.5 T apparatus using a body coil. The lesions were divided into a responder group and a nonresponder group according to whether the lesion size decreased by 50% or not. With MRI, shading was seen in 25 of 27 lesions (93%) from the nonresponder group, but in only 6 of 22 (27%) from the responder group. Low SI rim was seen in 59% of the responders and 89% of the nonresponders. Multiplicity in 68% of the responders and in 85% of the nonresponders and irregularity in 41% of the responders and in 78% of the nonresponders were shown. Multiple logistic analysis revealed shading was the most important factor in prediction of the response to hormone therapy. Shading was an important sign in evaluating the response of endometriomas to hormone therapy. MRI may assist in selecting the appropriate therapy for endometriomas. 16 refs., 3 figs., 2 tabs.

  11. Characterization and expression profile of the ovarian cytochrome P-450 aromatase (cyp19A1) gene during thermolabile sex determination in Pejerrey, Odontesthes bonariensis

    USGS Publications Warehouse

    Karube, M.; Fernandino, J.I.; Strobl-Mazzulla, P.; Strussmann, C.A.; Yoshizaki, G.; Somoza, G.M.; Patino, R.

    2007-01-01

    Cytochrome P450 aromatase (cyp19) is an enzyme that catalyzes the conversion of androgens to estrogens and may play a role in temperature- dependent sex determination (TSD) of reptiles, amphibians, and fishes. In this study, the ovarian P450 aromatase form (cyp19A1) of pejerrey Odontesthes bonariensis, a teleost with marked TSD, was cloned and its expression profile evaluated during gonadal differentiation at feminizing (17??C, 100% females), mixed-sex producing (24 and 25??C, 73.3 and 26.7% females, respectively), and masculinizing (29??C, 0% females) temperatures. The deduced cyp19A1 amino acid sequence shared high identity (>77.8%) with that from other teleosts but had low identity (<61.8%) with brain forms (cyp19A2), including that of pejerrey itself. The tissue distribution analysis of cyp19A1 mRNA in adult fish revealed high expression in the ovary. Semi-quantitative reverse transcription polymerase chain reaction analysis of the bodies of larvae revealed that cyp19A1 expression increased before the appearance of the first histological signs of ovarian differentiation at the feminizing temperature but remained low at the masculinizing temperature. The expression levels at mixed-sex producing temperatures were bimodal rather than intermediate, showing low and high modal values similar to those at the feminizing and masculinizing temperatures, respectively. The population percentages of high and low expression levels at intermediate temperatures were proportional to the percentage of females and males, respectively, and high levels were first observed at about the time of sex differentiation of females. These results suggest that cyp19A1 is involved in the process of ovarian formation and possibly also in the TSD of pejerrey. ?? 2007 Wiley-Liss, Inc.

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

    DTIC Science & Technology

    2011-05-01

    is evaluated by quantitative real-time PCR (reported as fgSix1/ng 18s rRNA, Y Axis). Six1 transfected CaOV3 clones (last 4 data sets) have greater...DcR2 expression by quantitative real time PCR (qRT- PCR ). TRAIL sensitivity was also determined for each cell line (sensitive = IC50  50 ng/ml...characterized cell lines were analyzed for Six1 expression by qRT- PCR (reported as absent/below mean versus above mean relative expression, mean expression

  13. Identification of predictive factors of response to the BH3-mimetic molecule ABT-737: an ex vivo experiment in human serous ovarian carcinoma.

    PubMed

    Lheureux, Stéphanie; N'Diaye, Monique; Blanc-Fournier, Cécile; Dugué, Audrey Emmanuelle; Clarisse, Bénédicte; Dutoit, Soizic; Giffard, Florence; Abeilard, Edwige; Briand, Mélanie; Labiche, Alexandre; Grellard, Jean-Michel; Crouet, Hubert; Martin, Sandrine; Joly, Florence; Poulain, Laurent

    2015-03-01

    Ovarian cancers are addicted to Bcl-xL and Mcl-1, antiapoptotic members of the Bcl-2 family. Bcl-xL can be inhibited by the BH3-mimetic ABT-737. In vitro, ABT-737 can induce apoptosis of cancer cells, and its activity is potentiated by Mcl-1 inactivation. Herein, we assessed the sensitivity of human ovarian tumor nodes to ABT-737 when combined with carboplatin, which can indirectly inhibit Mcl-1. Fresh samples from 25 patients with high-grade serous ovarian cancer (HGSOC) who were chemo-naïve and had undergone surgery were prospectively exposed ex vivo to ABT-737 ± carboplatin. The treatment effect was studied on sliced tumor nodes by assessment of cleaved-caspase 3 immunostaining. We also studied the association between baseline Bcl-2 family protein expression (via immunohistochemistry) and the response of nodes to treatment. ABT-737 induced apoptosis as a single agent but its efficacy was not improved by the addition of carboplatin. Bim was frequently expressed (20/25) and its absence or low expression was associated with the absence of response to ABT-737, p value = 0.019 by Fisher's test and sensitivity = 93%, (95% confidence interval, 66-100). Moreover, we observed that in tumors in which Bim was expressed, a low expression of phospho-Erk1/2 or Mcl-1 improved the proportion of responses. This pilot study showed that ABT-737 has promise as monotherapy for HGSOC in a specific subgroup of tumors. Bim, Mcl-1, and phospho-Erk1/2 appeared to be relevant biomarkers that could be used for the selection of patients in the design of clinical trials using Navitoclax (an orally available compound related to ABT-737).

  14. Long-Term Moderate Oxidative Stress Decreased Ovarian Reproductive Function by Reducing Follicle Quality and Progesterone Production

    PubMed Central

    Lai, Zhiwen; Tian, Yong; Fang, Li; Wu, Meng; Xiong, Jiaqiang; Qin, Xian; Luo, Aiyue; Wang, Shixuan

    2016-01-01

    Ovarian aging is a long-term and complex process associated with a decrease in follicular quantity and quality. The damaging effects of reactive oxygen species (ROS) in ovarian aging and ovarian aging-associated disorders have received relatively little attention. Thus, we assessed if the oxidative stress induced by long-term (defined by the Environmental Protection Agency as at least 30 days in duration) moderate ozone inhalation reduced ovarian reserves, decreased ovarian function and induced ovarian aging-associated disorders. The expression of oxidative stress markers and antioxidant enzymes was used to determine the degree of oxidative stress. Ultrastructural changes in ovarian cells were examined via electron microscopy. The ovarian reserve was assessed by measuring multiple parameters, such as the size of the primordial follicle pool and anti-Müllerian hormone (AMH) expression. The estrous cycle, hormone levels and fertility status were investigated to assess ovarian function. To investigate ovarian aging-associated disorders, we utilized bone density and cardiovascular ultrasonography in mice. The levels of oxidized metabolites, such as 8-hydroxy-2´-deoxyguanosine (8-OHdG), 4-hydroxynonenal (4-HNE) and nitrotyrosine (NTY), significantly increased in ovarian cells in response to increased oxidative stress. The ultrastructural analysis indicated that lipid droplet formation and the proportion of mitochondria with damaged membranes in granulosa cells were markedly increased in ozone-exposed mice when compared with the control group. Ozone exposure did not change the size of the primordial follicle pool or anti-Müllerian hormone (AMH) expression. The estrogen concentration remained normal; however, progesterone and testosterone levels decreased. The mice exposed to ozone inhalation exhibited a substantial decrease in fertility and fecundity. No differences were revealed by the bone density or cardiovascular ultrasounds. These findings suggest that the

  15. Modulators of Response to Tumor Necrosis-Factor-Related Apoptosis Inducing Ligand (TRAIL) Therapy in Ovarian Cancer

    DTIC Science & Technology

    2010-04-01

    antibody, MORAb-003. Methods: FRα expression was examined in ovarian cell lines (SKOV3ip1, IGROV, HeyA8, A2780-par, and HIO -180) with fluorescence...IGROVand SKOV3ip1 cell lines both expressed high levels of FRα compared with the non-transformed ( HIO -180) cells. HeyA8 and A2780-par cell lines lacked

  16. Maternal obesity is associated with ovarian inflammation and up-regulation of early growth response factor 1

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Obesity impairs reproductive functions through multiple mechanisms, possibly through disruption of ovarian function. We hypothesized that increased adiposity will lead to a pro-inflammatory gene signature and up-regulation of Egr-1 protein in ovaries from obese (OB, n=7) compared to lean (LN, n=10) ...

  17. Identification and Functional Characterization of Somatic Mutations in Human MicroRNAs and their Responsive Elements in Target Genes in Ovarian Tumor Tissues

    DTIC Science & Technology

    2009-05-01

    sequenced 50 microRNAs in 75 OC tumor tissues . So far, seven novel somatic mutations were observed in seven primary or precursor miRNA genes. WE...f miRNA m ay be a hallmark of h uman cancers . M iRNA m isexpression m ight be due t o genetic mutations i n miRNA ge nes an d t heir responsive...15. SUBJECT TERMS microRNA ovarian cancer 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF

  18. Ovarian reserve testing: A user's guide.

    PubMed

    Tal, Reshef; Seifer, David B

    2017-02-21

    Ovarian reserve is a complex clinical phenomenon that is influenced by age, genetics and environmental variables. Although it is challenging to predict the rate of an individual's ovarian reserve decline, clinicians are often asked for advice about fertility potential and/or recommendations regarding the pursuit of fertility treatment options. The purpose of this review is to summarize the state-of-the-art of ovarian reserve testing (ORT), providing a guide for the Ob/Gyn generalist and reproductive endocrinologist. The ideal ovarian reserve test should be convenient, reproducible, display little if any intra- and inter-cycle variability and demonstrate high specificity to minimize the risk of wrongly diagnosing women as having diminished ovarian reserve and accurately identify those at greatest risk of developing ovarian hyperstimulation prior to fertility treatment. Evaluation of ovarian reserve can help to identify patients who will have poor response or hyper-response to ovarian stimulation for assisted reproductive technology (ART). Ovarian reserve testing should allow individualization of treatment protocols to achieve optimal response while minimizing safety risks. Ovarian reserve testing may inform patients regarding their reproductive lifespan and menopausal timing as well as aid in the counselling and selection of treatment for female cancer patients of reproductive age who receive gonadotoxic therapy. In addition, it may aid in establishing the diagnosis of polycystic ovary syndrome (PCOS) and provide insight into its severity. While there is currently no perfect ovarian reserve test, both antral follicular count (AFC) and antimullerian hormone (AMH) have good predictive value and are superior to day 3 FSH. The convenience of untimed sampling, age-specific values, availability of an automated platform and potential standardization of AMH assay, make this test the preferred biomarker for the evaluation of ovarian reserve in women.

  19. Biological Basis for Chemoprevention of Ovarian Cancer

    DTIC Science & Technology

    1999-10-01

    Since reduction of ovulation is protective against ovarian cancer, prevention may represent a feasible approach to decreasing mortality . To achieve a...cells, the use of levonorgestrel in chemoprevention of ovarian cancer is being explored in chickens and women. A chernoprevention trial is ongoing in...chickens and we will begin a trial to determine whether levonorgestrel induces apoptosis in the ovarian epithelium of women undergoing oophorectomy.

  20. Estrus response and fertility after a single cloprostenol treatment in dairy cows with various ovarian structures.

    PubMed

    Hatvani, Csilla; Balogh, Orsolya G; Endrődi, Tamás; Abonyi-Tóth, Zsolt; Holló, István; Kastelic, John P; Gábor, György

    2013-07-01

    The objective of this study was to determine rates of estrus and conception in lactating multiparous Holstein cows given 500 μg of cloprostenol intramuscularly after detection of the following ≥ 60 d after parturition: a solid corpus luteum (CL), a CL with a nonechodense cavity ≤ 20 mm in diameter (CLcav), a luteal cyst (cavity > 20 mm in diameter and a luteinized wall > 3 mm in diameter), or a follicular cyst (cavity > 20 mm and a luteinized wall ≤ 3 mm in diameter). The estrus rates were 335/419 (80.0%), 183/223 (82.1%), 170/182 (93.4%), and 44/87 (50.6%), respectively (P < 0.0001), and the conception rates 30 to 36 d after insemination among the estrous cows with an apparently normal mucus discharge were 130/285 (45.6%), 44/141 (31.2%), 39/79 (49.4%), and 19/30 (63.3%), respectively (P < 0.002). Compared with a solid CL, a CLcav did not affect the estrus rate but significantly reduced the conception rate (P < 0.05), and the estrus rates were significantly higher and lower in cows with a luteal or follicular cyst, respectively (P < 0.05).

  1. Estrus response and fertility after a single cloprostenol treatment in dairy cows with various ovarian structures

    PubMed Central

    Hatvani, Csilla; Balogh, Orsolya G.; Endrődi, Tamás; Abonyi-Tóth, Zsolt; Holló, István; Kastelic, John P.; Gábor, György

    2013-01-01

    The objective of this study was to determine rates of estrus and conception in lactating multiparous Holstein cows given 500 μg of cloprostenol intramuscularly after detection of the following ≥ 60 d after parturition: a solid corpus luteum (CL), a CL with a nonechodense cavity ≤ 20 mm in diameter (CLcav), a luteal cyst (cavity > 20 mm in diameter and a luteinized wall > 3 mm in diameter), or a follicular cyst (cavity > 20 mm and a luteinized wall ≤ 3 mm in diameter). The estrus rates were 335/419 (80.0%), 183/223 (82.1%), 170/182 (93.4%), and 44/87 (50.6%), respectively (P < 0.0001), and the conception rates 30 to 36 d after insemination among the estrous cows with an apparently normal mucus discharge were 130/285 (45.6%), 44/141 (31.2%), 39/79 (49.4%), and 19/30 (63.3%), respectively (P < 0.002). Compared with a solid CL, a CLcav did not affect the estrus rate but significantly reduced the conception rate (P < 0.05), and the estrus rates were significantly higher and lower in cows with a luteal or follicular cyst, respectively (P < 0.05). PMID:24101799

  2. Endocrine and Ovarian Changes in Response to the Ram Effect in Medroxyprogesterone Acetate-primed Corriedale Ewes During the Breeding and Nonbreeding Season

    PubMed Central

    Ungerfeld, R; Carbajal, B; Rubianes, E; Forsberg, M

    2005-01-01

    Two experiments were performed to determine the endocrine and ovarian changes in medroxyprogesterone acetate (MAP)-primed ewes after ram introduction. Experiment 1 was performed during the mid-breeding season with 71 ewes primed with an intravaginal MAP sponge for 12 days. While the control (C) ewes (n = 35) were in permanent contact with rams, the ram effect (RE) ewes (n = 36) were isolated for 34 days prior to contact with rams. At sponge withdrawal, all ewes were joined with eight sexually experienced marking Corriedale rams and estrus was recorded over the next 4 days. The ovaries were observed by laparoscopy 4–6 days after estrus. Four weeks later, pregnancy was determined by transrectal ultrasonography. In eight ewes from each group, ovaries were ultrasonographically scanned; FSH, LH, and estradiol-17β were measured every 12 hours until ovulation or 96 hours after estrus. The response to the rams was not affected by the fact that ewes had been kept or not in close contact with males before teasing. No differences were found in FSH, LH, estradiol-17β concentrations, growth of the ovulatory follicle, onset of estrus, ovulation rate, or pregnancy rate. Experiment 2 was performed with 14 ewes during the nonbreeding season. Ewes were isolated from rams for 1 month, and received a 6-day MAP priming. Ovaries were ultrasonographically scanned every 12 hours, and FSH, LH, estradiol-17β, and progesterone were measured. Ewes that ovulated and came into estrus had higher FSH and estradiol-17β levels before introduction of the rams than did ewes that had a silent ovulation. The endocrine pattern of the induced follicular phase of ewes that came into estrus was more similar to a normal follicular phase, than in ewes that had a silent ovulation. The follicle that finally ovulated tended to emerge earlier and in a more synchronized fashion in those ewes that did come into estrus. All ewes that ovulated had an LH surge and reached higher maximum FSH levels than ewes

  3. Functional Proteomic Analysis of Advanced Serous Ovarian Cancer using Reverse Phase Protein Array: TGFβ Pathway Signaling Indicates Response to Primary Chemotherapy

    PubMed Central

    Carey, Mark S.; Agarwal, Roshan; Gilks, Blake; Swenerton, Kenneth; Kalloger, Steve; Santos, Jennifer; Ju, Zhenlin; Lu, Yiling; Zhang, Fan; Coombes, Kevin; Miller, Dianne; Huntsman, David; Mills, Gordon B.; Hennessy, Bryan T

    2010-01-01

    Purpose: Using Reverse Phase Protein Array (RPPA) we measured protein expression associated with response to primary chemotherapy in patients with advanced-stage high-grade serous ovarian cancer. Experimental Design: Tumor samples were obtained from forty-five patients with advanced high-grade serous cancers from the Gynecology Tumor Bank at the British Columbia Cancer Agency. Treatment consisted of platinum-based chemotherapy following debulking surgery. Protein lysates were prepared from fresh frozen tumor samples and 80 validated proteins from signaling pathways implicated in ovarian carcinogenesis were measured by RPPA. Normalization of Ca-125 by the 3rd cycle of chemotherapy was chosen as the primary outcome measure of chemotherapy response. Logistic regression was used for multivariate analysis to identify protein predictors of Ca-125 normalization, and Cox regression to test for the association between protein expression and PFS. A significance level of p ≤ 0.05 was used. Results: The mean age at diagnosis was 56.8 years. EGFR, YKL-40 and several TGFβ pathway proteins (c-Jun N-terminal kinase JNK, JNK phosphorylated at residues 183 and 185, PAI-1, Smad3, TAZ) showed significant associations with Ca-125 normalization on univariate testing. On multivariate analysis, EGFR (p < 0.02), JNK (p < 0.01), and Smad3 (p < 0.04) were significantly associated with normalization of Ca-125. Contingency table analysis of pathway-classified proteins revealed that the selection of TGFβ pathway proteins was unlikely due to false discovery (p < 0.007, Bonferroni-adjusted). Conclusion: TGFβ pathway signaling likely plays an important role as a marker or mediator of chemoresistance in advanced serous ovarian cancer. On this basis, future studies to develop and validate a useful predictor of treatment failure are warranted. PMID:20460476

  4. Effects of eCG and FSH on ovarian response, recovery rate and number and quality of oocytes obtained by ovum pick-up in Holstein cows.

    PubMed

    Sendag, Sait; Cetin, Yunus; Alan, Muhammet; Hadeler, Klaus-Gerd; Niemann, Heiner

    2008-06-01

    The goal of the present study was to compare the ovarian response, oocyte yields per animal, and the morphological quality of oocytes collected by ultrasound guided follicular aspiration from Holstein cows treated either with FSH or eCG. Twenty four normal cyclic, German Holstein cows were randomly divided into two groups. Fourteen cows received 3000 IU eCG on day-4 prior to ovum pick-up (OPU) (day 0), 2 days later (day-2), 625 microg cloprostenol was administered. On day-1 GnRH was administered i.m. and 24h later OPU (day 0) was performed. In ten cows a total dose of 500 IU follicle stimulating hormone (Pluset) was administered intramuscularly in a constant dosage for 4 days with intervals of 12h, starting on day-5. Luteolysis was induced by application of 625 microg cloprostenol on day-2. On day-1 (24h after the last FSH treatment) GnRH was administered i.m. and 24h later OPU (day 0) was performed. Ovarian follicles were visualized on the ultrasound monitor, counted and recorded. All visible antral follicles were punctured. Recovered oocytes were graded morphologically based on the cumulus investment. Average follicle number in ovaries was higher in FSH group than eCG group (p<0.05). Oocyte yields per animal did not differ between FSH and eCG groups. The proportion of grade A oocytes was higher in the FSH group in the than eCG group (p<0.05). Likewise, rate of grade C oocytes in FSH group were lower than eCG group (p<0.05). In conclusion, these results suggest that ovarian response, follicle number in ovaries and oocyte quality are affected by the type of gonadotropin and FSH is better alternative than eCG for OPU treatment.

  5. Sex Reversal in C57BL/6J XY Mice Caused by Increased Expression of Ovarian Genes and Insufficient Activation of the Testis Determining Pathway

    PubMed Central

    Correa, Stephanie M.; Washburn, Linda L.; Kahlon, Ravi S.; Musson, Michelle C.; Bouma, Gerrit J.; Eicher, Eva M.; Albrecht, Kenneth H.

    2012-01-01

    Sex reversal can occur in XY humans with only a single functional WT1 or SF1 allele or a duplication of the chromosome region containing WNT4. In contrast, XY mice with only a single functional Wt1, Sf1, or Wnt4 allele, or mice that over-express Wnt4 from a transgene, reportedly are not sex-reversed. Because genetic background plays a critical role in testis differentiation, particularly in C57BL/6J (B6) mice, we tested the hypothesis that Wt1, Sf1, and Wnt4 are dosage sensitive in B6 XY mice. We found that reduced Wt1 or Sf1 dosage in B6 XYB6 mice impaired testis differentiation, but no ovarian tissue developed. If, however, a YAKR chromosome replaced the YB6 chromosome, these otherwise genetically identical B6 XY mice developed ovarian tissue. In contrast, reduced Wnt4 dosage increased the amount of testicular tissue present in Sf1+/− B6 XYAKR, Wt1+/− B6 XYAKR, B6 XYPOS, and B6 XYAKR fetuses. We propose that Wt1B6 and Sf1B6 are hypomorphic alleles of testis-determining pathway genes and that Wnt4B6 is a hypermorphic allele of an ovary-determining pathway gene. The latter hypothesis is supported by the finding that expression of Wnt4 and four other genes in the ovary-determining pathway are elevated in normal B6 XX E12.5 ovaries. We propose that B6 mice are sensitive to XY sex reversal, at least in part, because they carry Wt1B6 and/or Sf1B6 alleles that compromise testis differentiation and a Wnt4B6 allele that promotes ovary differentiation and thereby antagonizes testis differentiation. Addition of a “weak” Sry allele, such as the one on the YPOS chromosome, to the sensitized B6 background results in inappropriate development of ovarian tissue. We conclude that Wt1, Sf1, and Wnt4 are dosage-sensitive in mice, this dosage-sensitivity is genetic background-dependant, and the mouse strains described here are good models for the investigation of human dosage-sensitive XY sex reversal. PMID:22496664

  6. Metabolic Regulation of Ovarian Cancer Cell Death

    DTIC Science & Technology

    2012-07-01

    Following treatment with chemotherapeutic agents, responsive ovarian cancer cells undergo apoptotic cell death . Several groups have shown that the...apoptotic protease, caspase 2 (C2), is an essential activator of cell death in ovarian cancer cells treated with cisplatin and we have found, by knock

  7. Possibilities and limits of ovarian reserve testing in ART.

    PubMed

    La Marca, Antonio; Argento, Cindy; Sighinolfi, Giovanna; Grisendi, Valentina; Carbone, Marilena; D'Ippolito, Giovanni; Artenisio, Alfredo Carducci; Stabile, Gaspare; Volpe, Annibale

    2012-03-01

    Markers of ovarian reserve are associated with ovarian aging as they decline with chronologic age, and hence may predict stages of reproductive aging including the menopause transition. Assessment of ovarian reserve include measurement of serum follicle stimulating hormone (FSH), anti-M�llerian hormone (AMH), and inhibin-B. Ultrasound determination of antral follicle count (AFC), ovarian vascularity and ovarian volume also can have a role. The clomiphene citrate challenge test (CCCT), exogenous FSH ovarian reserve test (EFORT), and GnRH-agonist stimulation test (GAST) are dynamic methods that have been used in the past to assess ovarian reserve. In infertile women, ovarian reserve markers can be used to predict low and high oocyte yield and treatment failure in women undergoing in vitro fertilization. However the markers may have limitations when an in depth analysis of their accuracy, cost, convenience, and utility is performed. As ovarian reserve markers may permit the identification of both the extremes of ovarian stimulation, a possible role for their measurement may be in the individualization of treatment strategies in order to reduce the clinical risk of ART along with optimized treatment burden. It is fundamental to clarify the cost/benefit of its use in the ovarian reserve testing before initiation of an IVF cycle and whether the ovarian reserve markers-determined strategy of ovarian stimulation for assisted conception may be associated to improved live birth rate.

  8. Does pre-treatment with micronized progesterone affect the ovarian response to a gonadotropin releasing hormone agonist flare-up protocol?

    PubMed

    Loutradis, D; Stefanidis, K; Drakakis, P; Kallianidis, K; El Sheikh, A; Milingos, S; Siskos, K; Michalas, S

    2003-04-01

    The purpose of this study was to investigate the ovarian response and the receptivity of the endometrium in women pre-treated with micronized progesterone. Eighty-two normogonodotropic women undergoing in vitro fertilization were studied. Thirty received micronized progesterone 1500 mg/day from day 21 of the cycle for a minimum of 2 weeks, and 52 did not receive micronized progesterone (control group). A gonadotropin releasing hormone agonist (GnRH-a) was administered to all the patients in the follicular phase (flare-up). Twenty-five cycles were cancelled for fertilization failure due to male factor, 12 (40%) in the progesterone group and 13 (25%) in the control group (p = 0.271). There was no difference in the number of oocytes retrieved (7.3 +/- 5 vs. 8.2 +/- 4), fertilization rate (50.8% vs. 65%), clinical pregnancy rate (16.6% vs. 25%) or implantation rate (8% vs. 14%). In the progesterone group cases without fertilization, we performed two biopsies to evaluate the receptivity of the endometrium. Pinopode expression was noted 7 days after oocyte retrieval. It seems that the administration of micronized progesterone in the previous cycle does not affect the ovarian response to the combination of follicular phase GnRH-a and gonadotropins, nor the receptivity of the endometrium.

  9. Interleukin-12 requires initial CD80-mediated T-cell activation to support immune responses toward human breast and ovarian carcinoma.

    PubMed

    Gückel, B; Meyer, G C; Rudy, W; Batrla, R; Meuer, S C; Bastert, G; Wallwiener, D; Moebius, U

    1999-01-01

    One possible reason for the poor immunogenicity of tumors is the induction of peripheral tolerance by tumor cells that fail to deliver costimulatory signals. Furthermore, T cells stimulated with wild-type tumor cells often fail to secrete cytokines. The present study has been undertaken to identify cytokines that cooperate with CD80 in T-cell activation in vitro toward human breast and ovarian carcinoma cell lines. Tumor cell-mediated T-lymphocyte activation was analyzed directly in allogeneic mixed lymphocyte/tumor cell cultures as proliferation and effector functions were assessed in cytotoxic T-cell assays. Interleukin-7 (IL-7) amplified the proliferative response toward CD80-transfected breast and ovarian carcinomas and stimulated predominantly CD4+ T lymphocytes. IL-12 represses the proliferative response of naive T cells but cooperates with CD80-mediated activation during secondary stimulations. In long-term T-cell cultures, IL-12 synergizes with CD80 expression to stimulate cytolytic CD8+ T-cell lines, which recognize a breast carcinoma line in a human histocompatibility leukocyte antigen-restricted manner. These studies illustrate that costimulation is necessary for tumor cells to function as alloantigen-presenting cells. Furthermore, when added after the priming of T cells with CD80-transfected tumor cells, IL-12 could be helpful in propagating sufficient T-cell numbers to be used in adoptive transfers during cellular immunotherapy.

  10. The significance of antral follicle size prior to stimulation in predicting ovarian response in a multiple dose GnRH antagonist protocol.

    PubMed

    Lai, Qiaohong; Chen, Cai; Zhang, Zhijun; Zhang, Shu; Yu, Qilin; Yang, Ping; Hu, Jun; Wang, Cong-Yi

    2013-01-01

    Prediction of ovarian responses prior to stimulation is not only useful for patient counseling, but also important in tailoring the optimal dosage of gonadotrophin for individual patients. By prospectively study of 214 women undergoing in vitro fertilization and embryo transfer (IVF-ET) treatment, we obtained data supporting that antral follicle size could be an additional valuable predictive marker other than the antral follicle count (AFC) in predicting ovarian response. Our studies revealed that AFC achieved the best predictive value in relation to the number of oocyte obtained, followed by antral follicle size, basal follicle stimulating hormone (FSH) and body mass index (BMI). Unlike AFC, antral follicle size was noted to be negatively correlated with the dosage (R = -0.493) and duration (R = -0.465) of rFSH stimulation. Antral follicle size was also found with higher negative regression coefficient (B = -0.661) as compared with that of basal FSH concentration (B = -0.326) and BMI (b = -0.281). More importantly, women with antral follicle size 6-7 mm showed significantly higher AFC, oocytes retrieved, fertilized oocytes and grade I/II embryos along with much lower transfer cycle cancellation rate (7.5% vs. 16-17%). Together, our data suggest that basal antral follicle size could be a valued predictive marker in women with IVF-ET treatment, in which women with antral follicle size 6-7 mm are likely predisposed to better IVF-ET outcomes.

  11. Premature Progesterone Rise Positively Correlates with Clinical Pregnancy Rate in In Vitro Fertilization (IVF) and Intracytoplasmic Sperm Injection (ICSI) Patients with good Ovarian Response.

    PubMed

    Cui, Na; Zhang, Jie; Xu, Yueming; Jiang, Lei; Yang, Aimin; Hao, Guimin

    2017-03-28

    Infertility affects millions of couples worldwide resulting in distress and depression. In the past several decades, in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) have been developed with high efficiency and success rate. The possible effects of gonadotropin administration on follicular metabolism have been discussed but the outcomes remain controversial. The aim of this study was to identify whether serum progesterone on the day of human chorionic gonadotropin (hCG) administration and the ratio of serum progesterone and the number of oocyte retrieved (P/O) had a predictive role for the outcomes of IVF/ICSI. Eight hundred and twenty-five patients were enrolled between January 2012 and December 2012. A positive correlation between progesterone and IVF/ICSI outcomes were found in patients with good ovarian response using receiver operating characteristic (ROC) curve. We found that when progesterone level was higher than 1.04 ng/ml in good ovarian responses, the implantation rate and clinical pregnancy rate were both reduced compared to the rates in patients exhibiting lower progesterone level (progesterone≤1.04 ng/ml). Moreover, the rise of serum progesterone on the day of hCG was negatively correlated with luteinizing hormone (LH) level. This study used 1.04 ng/ml as a definition of progesterone elevation and an adverse effect of serum progesterone rise was observed on clinical pregnancy rate.

  12. Nasal immunization with inhibin DNA vaccine delivered by attenuated Salmonella choleraesuis for improving ovarian responses and fertility in cross-bred buffaloes.

    PubMed

    Liu, Q; Rehman, Z U; Liu, J J; Han, L; Liu, X R; Yang, L G

    2017-04-01

    This study was conducted to determine the effect of immunization with inhibin DNA vaccine delivered by attenuated Salmonella choleraesuis on ovarian responses and fertility in cross-bred buffaloes. A total of 134 cross-bred buffaloes were divided into four groups: groups T1 (n = 34), T2 (n = 35) and T3 (n = 31) were nasal immunized twice a day with 10 ml of 1 × 10(10)  CFU/ml of the C501 (pVAX-asd-IS) vaccine for 5, 3 and 1 day, respectively. Group C (n = 34) was nasal immunized with 10 ml PBS for 5 days. All animals were immunized twice with an interval of 14 days and administered with 200 μg of a GnRH analogue on day 28, 0.5 mg PGF2α on day 35 and 200 μg of the same GnRH analogue on day 37. TAI was performed at 18 and 24 hr after the second GnRH treatment. Fourteen days after primary immunization, C501 (pVAX-asd-IS) elicited significant immune responses, and anti-inhibin IgG antibody titres in group T1 were significantly higher (p < .01) than groups T3 and C. After the second GnRH treatment, the growth speed of the dominant follicles in group T1 was significantly faster (p < .05) than groups T3 and C. The number and diameter of large follicles (≥10 mm) as well as ovulatory follicles in group T1 were the greatest in all groups, resulting in a greater conception rate in buffaloes with positive anti-inhibin antibodies. These results demonstrate that immunization with the C501 (pVAX-asd-IS) vaccine, coupled with the Ovsynch protocol, could be used as an alternative approach to improve reproductive performance in cross-bred buffaloes.

  13. Ovarian Autoantibodies Predict Ovarian Cancer

    DTIC Science & Technology

    2010-11-01

    ovarian adenocarcinomas from laying hens. Gynecol Oncol, 2007; 104: 192-198. 506 25. Hales DB, Zhuge Y, Lagman JA, Ansenberger K, Mahon C, Barua A...Ultrasound Med 2010, 29:173-182. 479 (19) Hales DB, Zhuge Y, Lagman JA, Ansenberger K, Mahon C, Barua A et al: 480 Cyclooxygenases expression and...adenocarcinomas from laying hens. Gynecol Oncol 2007, 507 104:192-198. 508 (30) Ansenberger K, Zhuge Y, Lagman JA, Richards C, Barua A, Bahr JM

  14. MRI reveals the in vivo cellular and vascular response to BEZ235 in ovarian cancer xenografts with different PI3-kinase pathway activity

    PubMed Central

    Cebulla, J; Huuse, E M; Pettersen, K; van der Veen, A; Kim, E; Andersen, S; Prestvik, W S; Bofin, A M; Pathak, A P; Bjørkøy, G; Bathen, T F; Moestue, S A

    2015-01-01

    Background: The phosphoinositide-3 kinase (PI3K) pathway is an attractive therapeutic target. However, difficulty in predicting therapeutic response limits the clinical implementation of PI3K inhibitors. This study evaluates the utility of clinically relevant magnetic resonance imaging (MRI) biomarkers for noninvasively assessing the in vivo response to the dual PI3K/mTOR inhibitor BEZ235 in two ovarian cancer models with differential PI3K pathway activity. Methods: The PI3K signalling activity of TOV-21G and TOV-112D human ovarian cancer cells was investigated in vitro. Cellular and vascular response of the xenografts to BEZ235 treatment (65 mg kg−1, 3 days) was assessed in vivo using diffusion-weighted (DW) and dynamic contrast-enhanced (DCE)-MRI. Micro-computed tomography was performed to investigate changes in vascular morphology. Results: The TOV-21G cells showed higher PI3K signalling activity than TOV-112D cells in vitro and in vivo. Treated TOV-21G xenografts decreased in volume and DW-MRI revealed an increased water diffusivity that was not found in TOV-112D xenografts. Treatment-induced improvement in vascular functionality was detected with DCE-MRI in both models. Changes in vascular morphology were not found. Conclusions: Our results suggest that DW- and DCE-MRI can detect cellular and vascular response to PI3K/mTOR inhibition in vivo. However, only DW-MRI could discriminate between a strong and weak response to BEZ235. PMID:25535727

  15. Paraneoplastic syndromes in patients with ovarian neoplasia.

    PubMed

    Hudson, C N; Curling, M; Potsides, P; Lowe, D G

    1993-04-01

    The prevalence of several paraneoplastic syndromes associated with ovarian cancer was determined from a clinicopathological study of 908 patients with primary ovarian malignancy in the North East Thames Region. The diversity and rarity of these manifestations are great and the explanation for them is difficult. Circumstantial evidence suggests that in some cases an autoimmune phenomenon is the most plausible cause.

  16. Increased levels of oxidative and carbonyl stress markers in normal ovarian cortex surrounding endometriotic cysts.

    PubMed

    Di Emidio, Giovanna; D'Alfonso, Angela; Leocata, Pietro; Parisse, Valentina; Di Fonso, Adina; Artini, Paolo Giovanni; Patacchiola, Felice; Tatone, Carla; Carta, Gaspare

    2014-11-01

    Many evidence support the view that endometriotic cyst may exert detrimental effect on the surrounding ovarian microenvironment so representing a risk to functionality of adjacent follicles. Patients with benign ovarian cyst (endometriotic, follicular and dermoid cysts) subjected to laparoscopic cystectomy were enrolled in the present retrospective study in order to analyze whether endometriotic tissue could negatively affect the surrounding normal ovarian cortex more severely than other ovarian cysts. To this end we carried out immunohistochemistry analysis and comparative determination of the transcription factor FOXO3A, oxidized DNA adduct 8-OHdG (8-hydroxy-2'-deoxyguanosine) and damaged proteins known as AGEs (Advanced Glycation End products) as markers of ovarian stress response and molecular damage. Our results show that all the markers analyzed were present in normal ovarian tissue surrounding benign cysts. We observed higher levels of FOXO3A (15.90 ± 0.28), 8-OHdG (13.33 ± 2.07) and AGEs (12.58 ± 4.34) staining in normal ovarian cortex surrounding endometriotic cysts in comparison with follicular cysts (9.04 ± 0.29, 2.67 ± 2.67, 11.31 ± 2.95, respectively) and dermoid cysts (2.02 ± 0.18, 4.33 ± 2.58 and 10.56 ± 4.03, respectively). These results provide evidence that ovarian endometrioma is responsible for more severe alterations to cellular biomolecules than follicular and dermoid cysts.

  17. WNT5a is required for normal ovarian follicle development and antagonizes gonadotropin responsiveness in granulosa cells by suppressing canonical WNT signaling.

    PubMed

    Abedini, Atefeh; Zamberlam, Gustavo; Lapointe, Evelyne; Tourigny, Catherine; Boyer, Alexandre; Paquet, Marilène; Hayashi, Kanako; Honda, Hiroaki; Kikuchi, Akira; Price, Christopher; Boerboom, Derek

    2016-04-01

    Whereas the roles of the canonical wingless-type MMTV (mouse mammary tumor virus) integration site family (WNT) signaling pathway in the regulation of ovarian follicle growth and steroidogenesis are now established, noncanonical WNT signaling in the ovary has been largely overlooked. Noncanonical WNTs, including WNT5a and WNT11, are expressed in granulosa cells (GCs) and are differentially regulated throughout follicle development, but their physiologic roles remain unknown. Using conditional gene targeting, we found that GC-specific inactivation ofWnt5a(but notWnt11) results in the female subfertility associated with increased follicular atresia and decreased rates of ovulation. Microarray analyses have revealed that WNT5a acts to down-regulate the expression of FSH-responsive genesin vitro, and corresponding increases in the expression of these genes have been found in the GCs of conditional knockout mice. Unexpectedly, we found that WNT5a regulates its target genes not by signalingviathe WNT/Ca(2+)or planar cell polarity pathways, but rather by inhibiting the canonical pathway, causing both β-catenin (CTNNB1) and cAMP responsive element binding (CREB) protein levels to decreaseviaa glycogen synthase kinase-3β-dependent mechanism. We further found that WNT5a prevents follicle-stimulating hormone and luteinizing protein from up-regulating the CTNNB1 and CREB proteins and their target genes, indicating that WNT5a functions as a physiologic inhibitor of gonadotropin signaling. Together, these findings identify WNT5a as a key regulator of follicle development and gonadotropin responsiveness.-Abedini, A., Zamberlam, G., Lapointe, E., Tourigny, C., Boyer, A., Paquet, M., Hayashi, K., Honda, H., Kikuchi, A., Price, C., Boerboom, D. WNT5a is required for normal ovarian follicle development and antagonizes gonadotropin responsiveness in granulosa cells by suppressing canonical WNT signaling.

  18. WNT5a is required for normal ovarian follicle development and antagonizes gonadotropin responsiveness in granulosa cells by suppressing canonical WNT signaling

    PubMed Central

    Abedini, Atefeh; Zamberlam, Gustavo; Lapointe, Evelyne; Tourigny, Catherine; Boyer, Alexandre; Paquet, Marilène; Hayashi, Kanako; Honda, Hiroaki; Kikuchi, Akira; Price, Christopher; Boerboom, Derek

    2015-01-01

    Whereas the roles of the canonical wingless-type MMTV (mouse mammary tumor virus) integration site family (WNT) signaling pathway in the regulation of ovarian follicle growth and steroidogenesis are now established, noncanonical WNT signaling in the ovary has been largely overlooked. Noncanonical WNTs, including WNT5a and WNT11, are expressed in granulosa cells (GCs) and are differentially regulated throughout follicle development, but their physiologic roles remain unknown. Using conditional gene targeting, we found that GC-specific inactivation of Wnt5a (but not Wnt11) results in the female subfertility associated with increased follicular atresia and decreased rates of ovulation. Microarray analyses have revealed that WNT5a acts to down-regulate the expression of FSH-responsive genes in vitro, and corresponding increases in the expression of these genes have been found in the GCs of conditional knockout mice. Unexpectedly, we found that WNT5a regulates its target genes not by signaling via the WNT/Ca2+ or planar cell polarity pathways, but rather by inhibiting the canonical pathway, causing both β-catenin (CTNNB1) and cAMP responsive element binding (CREB) protein levels to decrease via a glycogen synthase kinase-3β-dependent mechanism. We further found that WNT5a prevents follicle-stimulating hormone and luteinizing protein from up-regulating the CTNNB1 and CREB proteins and their target genes, indicating that WNT5a functions as a physiologic inhibitor of gonadotropin signaling. Together, these findings identify WNT5a as a key regulator of follicle development and gonadotropin responsiveness.—Abedini, A., Zamberlam, G., Lapointe, E., Tourigny, C., Boyer, A., Paquet, M., Hayashi, K., Honda, H., Kikuchi, A., Price, C., Boerboom, D. WNT5a is required for normal ovarian follicle development and antagonizes gonadotropin responsiveness in granulosa cells by suppressing canonical WNT signaling. PMID:26667040

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

    PubMed Central

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

    2016-01-01

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

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

    DTIC Science & Technology

    2009-04-01

    was minimally expressed in the nontrans- formed HIO -180 ovarian epithelial cells, but was detected at high levels in the HeyA8, HeyA8-MDR, SKOV3ip1...lines (SKOV3ip1, IGROV, HeyA8, A2780-par, and HIO -180) with fluorescence-activated cell sorting analysis. In vitro (cell viability, migration...with the non-transformed ( HIO -180) cells. HeyA8 and A2780-par cell lines lacked FRα expression. In vivo, MORAb-003 led to 44 and 84% decreases in

  1. The rate of high ovarian response in women identified at risk by a high serum AMH level is influenced by the type of gonadotropin.

    PubMed

    Arce, Joan-Carles; Klein, Bjarke M; La Marca, Antonio

    2014-06-01

    The aim was to compare ovarian response and clinical outcome of potential high-responders after stimulation with highly purified menotropin (HP-hMG) or recombinant follicle-stimulating hormone (rFSH) for in vitro fertilisation/intracytoplasmic sperm injection. Retrospective analysis was performed on data collected in two randomized controlled trials, one conducted following a long GnRH agonist protocol and the other with an antagonist protocol. Potential high-responders (n = 155 and n = 188 in the agonist and antagonist protocol, respectively) were defined as having an initial anti-Müllerian hormone (AMH) value >75th percentile (5.2 ng/ml). In both protocols, HP-hMG stimulation in women in the high AMH category was associated with a significantly lower occurrence of high response (≥15 oocytes retrieved) than rFSH stimulation; 33% versus 51% (p = 0.025) and 31% versus 49% (p = 0.015) in the long agonist and antagonist protocol, respectively. In the potential high-responder women, trends for improved live birth rate were observed with HP-hMG compared with rFSH (long agonist protocol: 33% versus 20%, p = 0.074; antagonist protocol: 34% versus 23%, p = 0.075; overall population: 34% versus 22%, p = 0.012). In conclusion, the type of gonadotropin used for ovarian stimulation influences high-response rates and potentially clinical outcome in women identified as potential high-responders.

  2. Neuroscience and legal determination of criminal responsibility.

    PubMed

    Eastman, Nigel; Campbell, Colin

    2006-04-01

    Neuroscience is increasingly identifying associations between biology and violence that appear to offer courts evidence relevant to criminal responsibility. In addition, in a policy era of 'zero tolerance of risk', evidence of biological abnormality in some of those who are violent, or biological markers of violence, may be seized on as a possible basis for preventive detention in the interest of public safety. However, there is a mismatch between questions that the courts and society wish answered and those that neuroscience is capable of answering. This poses a risk to the proper exercise of justice and to civil liberties.

  3. Determinants of immunogenic response to protein therapeutics.

    PubMed

    Singh, Satish K; Cousens, Leslie P; Alvarez, David; Mahajan, Pramod B

    2012-09-01

    Protein therapeutics occupy a very significant position in the biopharmaceutical market. In addition to the preclinical, clinical and post marketing challenges common to other drugs, unwanted immunogenicity is known to affect efficacy and/or safety of most biotherapeutics. A standard set of immunogenicity risk factors are routinely used to inform monitoring strategies in clinical studies. A number of in-silico, in vivo and in vitro approaches have also been employed to predict immunogenicity of biotherapeutics, but with limited success. Emerging data also indicates the role of immune tolerance mechanisms and impact of several product-related factors on modulating host immune responses. Thus, a comprehensive discussion of the impact of innate and adaptive mechanisms and molecules involved in induction of host immune responses on immunogenicity of protein therapeutics is needed. A detailed understanding of these issues is essential in order to fully exploit the therapeutic potential of this class of drugs. This Roundtable Session was designed to provide a common platform for discussing basic immunobiological and pharmacological issues related to the role of biotherapeutic-associated risk factors, as well as host immune system in immunogenicity against protein therapeutics. The session included overview presentations from three speakers, followed by a panel discussion with audience participation.

  4. Study on the proportion and determinants of polycystic ovarian syndrome among health sciences students in South India

    PubMed Central

    Joseph, Nitin; Reddy, Aditya G. R.; Joy, Divya; Patel, Vishakha; Santhosh, Pooja; Das, Shatarupa; Reddy, Siddharth K.

    2016-01-01

    Introduction: Polycystic ovarian syndrome (PCOS) constitutes most cases of endocrine disorder among females. Objectives: This study was done to assess the proportion of university students with PCOS and to study its risk factors. Materials and Methods: Data were collected from students of a private medical, dental, and nursing college using a self-administered questionnaire. Height and weight of all participants were recorded by standard procedures. Results: The mean age of students was 20.4 ΁ 1.5 years. Of the 480 participants, 39 (8.1%) were already diagnosed with PCOS. Out of the remaining 441 participants, 40 (9.1%) were at high risk, and 401 (90.9%) were at low risk for PCOS. Greater proportion of PCOS cases was seen in the age group 23-25 years (P = 0.026), among those with family history of PCOS (P = 0.002), among those who were permanent residents of urban areas (P = 0.048), and among those who were overweight or obese (P = 0.004). About 90% of PCOS cases and those at high risk for PCOS, each had difficulty in controlling excess weight or were experiencing difficulty in maintaining ideal weight. About 36 (92.3%) of PCOS cases and all those at high risk had emotional problems such as feeling moody or experiencing fatigability over the previous 2 weeks. Conclusion: PCOS is a common disorder among young women in this settings and this warrants periodic screening activities. A multidisciplinary approach is required to bring about lifestyle modification and help those with emotional problems due to this endocrine disorder. PMID:27433068

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

    SciTech Connect

    Zhan, Yu; Abi Saab, Widian F.; Modi, Nidhi; Stewart, Amanda M.; Liu, Jinsong; Chadee, Deborah N.

    2012-08-15

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

  6. Comparative ovarian microarray analysis of juvenile hormone-responsive genes in water flea Daphnia magna: potential targets for toxicity.

    PubMed

    Toyota, Kenji; Williams, Timothy D; Sato, Tomomi; Tatarazako, Norihisa; Iguchi, Taisen

    2017-03-01

    The freshwater zooplankton Daphnia magna has been extensively employed in chemical toxicity tests such as OECD Test Guidelines 202 and 211. Previously, it has been demonstrated that the treatment of juvenile hormones (JHs) or their analogues to female daphnids can induce male offspring production. Based on this finding, a rapid screening method for detection of chemicals with JH-activity was recently developed using adult D. magna. This screening system determines whether a chemical has JH-activity by investigating the male offspring inducibility. Although this is an efficient high-throughput short-term screening system, much remains to be discovered about JH-responsive pathways in the ovary, and whether different JH-activators act via the same mechanism. JH-responsive genes in the ovary including developing oocytes are still largely undescribed. Here, we conducted comparative microarray analyses using ovaries from Daphnia magna treated with fenoxycarb (Fx; artificial JH agonist) or methyl farnesoate (MF; a putative innate JH in daphnids) to elucidate responses to JH agonists in the ovary, including developing oocytes, at a JH-sensitive period for male sex determination. We demonstrate that induction of hemoglobin genes is a well-conserved response to JH even in the ovary, and a potential adverse effect of JH agonist is suppression of vitellogenin gene expression, that might cause reduction of offspring number. This is the first report demonstrating different transcriptomics profiles from MF and an artificial JH agonist in D. magna ovary, improving understanding the tissue-specific mode-of-action of JH. Copyright © 2016 John Wiley & Sons, Ltd.

  7. Ovarian arteries with bilateral unusual courses.

    PubMed

    Sulak, Osman; Albay, Soner; Tagil, Suleyman M; Malas, Mehmet A

    2005-09-01

    Bilateral unusual coursed ovarian arteries were found in a 45-year-old female cadaver. The ovarian arteries arose from the abdominal aorta at a level inferior to the corpus of L1 vertebra bilaterally. The right ovarian artery was coursing behind the inferior vena cava. The left one was coursing between the left renal artery and vein upward to the level of the inferior part of the body of Th12 vertebra. At the level of Th12 vertebra, it turned caudally and proceeded downward between the anterior-inferior and posterior segmental renal veins. On both sides, ovarian arteries were on their normal routes below the L2 vertebra accompanying the ovarian veins. The variation determined by this study would reduce possible complications of nephrectomy operations that urologists, gynecologists and other related surgeons may encounter.

  8. HOX genes in ovarian cancer.

    PubMed

    Kelly, Zoë L; Michael, Agnieszka; Butler-Manuel, Simon; Pandha, Hardev S; Morgan, Richard Gl

    2011-09-09

    The HOX genes are a family of homeodomain-containing transcription factors that determine cellular identity during development. Here we review a number of recent studies showing that HOX genes are strongly expressed in ovarian cancer, and that in some cases the expression of specific HOX genes is sufficient to confer a particular identity and phenotype upon cancer cells. We also review the recent advances in elucidating the different functions of HOX genes in ovarian cancer. A literature search was performed using the search terms HOX genes (including specific HOX genes), ovarian cancer and oncogenesis. Articles were accessed through searches performed in ISI Web of Knowledge, PubMed and ScienceDirect. Taken together, these studies have shown that HOX genes play a role in the oncogenesis of ovarian cancer and function in the inhibition of apoptosis, DNA repair and enhanced cell motility. The function of HOX genes in ovarian cancer oncogenesis supports their potential role as prognostic and diagnostic markers, and as therapeutic targets in this disease.

  9. Assessment of ovarian reserve: is there still a role for ovarian biopsy in the light of new data?

    PubMed

    Lass, Amir

    2004-03-01

    Ovarian reserve depends on the number of primordial follicles in the ovarian cortex. It was suggested that determining the follicular density directly by obtaining ovarian biopsy might be more accurate than current indirect biochemical and ultrasonic tests, especially for women in the later stage of their reproductive life. It might also be important and beneficial for young patients having chemotherapy for malignant disease in whom the ovarian tissue should be considered for reimplantation after recovery. The advantages and pitfalls of obtaining ovarian biopsy in these cases are discussed in light of new emerging data on the natural distribution of primordial follicles in the human ovary and its implications.

  10. Quantity and clinical relevance of circulating endothelial progenitor cells in human ovarian cancer

    PubMed Central

    2010-01-01

    Background Circulating bone marrow-derived endothelial progenitor cells (EPCs) have been reported to participate in tumor angiogenesis and growth; however, the role of circulating EPCs in tumor progression is controversial. The role of circulating EPCs in ovarian cancer progression and angiogenesis has not yet been investigated. Methods The number of circulating EPCs in the peripheral blood in 25 healthy volunteers and 42 patients with ovarian cancer was determined by flow cytometry. EPCs were defined by co-expression of CD34 and vascular endothelial growth factor receptor 2 (VEGFR2). In addition, we determined CD34 and VEGFR2 mRNA levels by real-time reverse transcription-polymerase chain reaction. Plasma levels of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) were determined by enzyme-linked immunosorbent assay. Results Circulating levels of EPCs were significantly increased in ovarian cancer patients, correlating with tumor stage and residual tumor size. Higher levels of EPCs were detected in patients with stage III and IV ovarian cancer than in patients with stage I and II disease. After excision of the tumor, EPCs levels rapidly declined. Residual tumor size greater than 2 cm was associated with significantly higher levels of EPCs. In addition, high circulating EPCs correlated with poor overall survival. Pretreatment CD34 mRNA levels were not significantly increased in ovarian cancer patients compared with healthy controls; however, VEGFR2 expression was increased, and plasma levels of VEGF and MMP-9 were also elevated. Conclusions Our results demonstrate the clinical relevance of circulating EPCs in ovarian cancer. EPCs may be a potential biomarker to monitor ovarian cancer progression and angiogenesis and treatment response. PMID:20334653

  11. Ovarian aging and premature ovarian failure

    PubMed Central

    Şükür, Yavuz Emre; Kıvançlı, İçten Balık; Özmen, Batuhan

    2014-01-01

    Physiological reproductive aging occurs as a result of a decrease in the number and quality of oocytes in ovarian cortex follicles. Although the reason for the decrease in the quality of the pool and follicular oocytes is not fully understood, endocrine, paracrine, genetic, and metabolic factors are thought to be effective. Nowadays, in order to understand the mechanisms of ovarian aging, genomic research has gained importance. The effect of co-factors, such as telomerase and ceramide, in the ovarian aging process is only getting ascertained with new research studies. The most important tests in the assessment of ovarian aging are antral follicle count and anti-Mullerian hormone. PMID:25317048

  12. What Is Ovarian Cancer?

    MedlinePlus

    ... to be similar to widespread ovarian cancer. Fallopian tube cancer This is another rare cancer that is ... to epithelial ovarian cancer. It begins in the tube that carries an egg from the ovary to ...

  13. Sex-determining region Y-box3 (SOX3) functions as an oncogene in promoting epithelial ovarian cancer by targeting Src kinase.

    PubMed

    Yan, Qin; Wang, Fangyuan; Miao, Yi; Wu, Xiaomei; Bai, Mingzhu; Xi, Xiaowei; Feng, Youji

    2016-09-01

    Ovarian cancer is one of the most common cancers which cause female mortality. The knowledge of ovarian cancer initiation and progression is critical to develop new therapeutic strategies to treat and prevent it. Recently, SOX3 has been reported to play a pivotal role in tumor progression. However, the clinical significance of SOX3 in human ovarian cancer remains elusive, and the identity of SOX3 in ovarian cancer initiation, progression, and the related underlying mechanism is unknown. In this study, we showed that SOX3 expression increased from benign and borderline to malignant ovarian tumors. Subsequently, we found that overexpression of SOX3 in EOC cells promoted proliferation, migration, and invasion, while restrained apoptosis and adhesion of ovarian cancer cells. In contrast, silencing of SOX3 gained the opposite results. Finally, we discovered SOX3 targeted Src kinase in EOC cells. These data imply that SOX3, acting as an oncogene in EOC, is not only a crucial factor in the carcinogenesis but also a promising therapeutic target for EOC.

  14. Environmentally induced epigenetic transgenerational inheritance of ovarian disease.

    PubMed

    Nilsson, Eric; Larsen, Ginger; Manikkam, Mohan; Guerrero-Bosagna, Carlos; Savenkova, Marina I; Skinner, Michael K

    2012-01-01

    The actions of environmental toxicants and relevant mixtures in promoting the epigenetic transgenerational inheritance of ovarian disease was investigated with the use of a fungicide, a pesticide mixture, a plastic mixture, dioxin and a hydrocarbon mixture. After transient exposure of an F0 gestating female rat during embryonic gonadal sex determination, the F1 and F3 generation progeny adult onset ovarian disease was assessed. Transgenerational disease phenotypes observed included an increase in cysts resembling human polycystic ovarian disease (PCO) and a decrease in the ovarian primordial follicle pool size resembling primary ovarian insufficiency (POI). The F3 generation granulosa cells were isolated and found to have a transgenerational effect on the transcriptome and epigenome (differential DNA methylation). Epigenetic biomarkers for environmental exposure and associated gene networks were identified. Epigenetic transgenerational inheritance of ovarian disease states was induced by all the different classes of environmental compounds, suggesting a role of environmental epigenetics in ovarian disease etiology.

  15. Environmentally Induced Epigenetic Transgenerational Inheritance of Ovarian Disease

    PubMed Central

    Nilsson, Eric; Larsen, Ginger; Manikkam, Mohan; Guerrero-Bosagna, Carlos; Savenkova, Marina I.; Skinner, Michael K.

    2012-01-01

    The actions of environmental toxicants and relevant mixtures in promoting the epigenetic transgenerational inheritance of ovarian disease was investigated with the use of a fungicide, a pesticide mixture, a plastic mixture, dioxin and a hydrocarbon mixture. After transient exposure of an F0 gestating female rat during embryonic gonadal sex determination, the F1 and F3 generation progeny adult onset ovarian disease was assessed. Transgenerational disease phenotypes observed included an increase in cysts resembling human polycystic ovarian disease (PCO) and a decrease in the ovarian primordial follicle pool size resembling primary ovarian insufficiency (POI). The F3 generation granulosa cells were isolated and found to have a transgenerational effect on the transcriptome and epigenome (differential DNA methylation). Epigenetic biomarkers for environmental exposure and associated gene networks were identified. Epigenetic transgenerational inheritance of ovarian disease states was induced by all the different classes of environmental compounds, suggesting a role of environmental epigenetics in ovarian disease etiology. PMID:22570695

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

    PubMed

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

    2012-01-01

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

  17. Nuclear TBLR1 as an ER corepressor promotes cell proliferation, migration and invasion in breast and ovarian cancer.

    PubMed

    Wu, Xinyu; Zhan, Yang; Li, Xin; Wei, Jianjun; Santiago, Larion; Daniels, Garrett; Deng, Fangming; Zhong, Xuelin; Chiriboga, Luis; Basch, Ross; Xiong, Sheng; Dong, Yan; Zhang, Xinmin; Lee, Peng

    2016-01-01

    Estrogen receptors (ER) play important roles in the development and progression of breast and ovarian cancers. ERs mediate transcriptional regulation through interaction with cofactors and binding to response elements within the regulatory elements of target genes. Here, we examined the expression and function of TBLR1/TBL1XR1, a core component of NCoR (nuclear receptor corepressor) and SMRT (silencing mediator of retinoic acid and thyroid receptor) corepressor complexes, in breast and ovarian cancers. We found that although TBLR1 is present in both the nucleus and cytoplasm of normal and neoplastic breast and ovarian cells, it is expressed at significantly higher levels in the nucleus of malignant breast and ovarian cells compared to benign cells. TBLR1 functions as an ER corepressor to inhibit ER-mediated transcriptional activation in both breast and ovarian cell lines, but it has no effect on androgen receptor (AR) mediated transcriptional activation in these cells. Furthermore, ectopic expression of nuclear TBLR1 in breast and ovarian cancer cells stimulates cell proliferation. The increased cell proliferation by nuclear TBLR1 is through both ER-independent and ER-dependent mechanisms as evidenced by increased growth in hormone-free medium and estrogen medium, as well as reduced growth with ER knockdown by siRNA. Nuclear TBLR1 overexpression also increased migration and invasion in both breast and ovarian cancer cells. Determining the functional relationship between TBLR1 and ER may provide insights to develop novel treatment strategies and improve response to hormonal therapy in breast and ovarian cancers.

  18. Response to an abnormal ovarian cancer-screening test result: test of the social cognitive processing and cognitive social health information processing models.

    PubMed

    Andrykowski, Michael A; Pavlik, Edward J

    2011-04-01

    All cancer screening tests produce a proportion of abnormal results requiring follow up. Consequently, the cancer-screening setting is a natural laboratory for examining psychological and behavioural response to a threatening health-related event. This study tested hypotheses derived from the social cognitive processing and cognitive-social health information processing models in trying to understand response to an abnormal ovarian cancer (OC) screening test result. Women (n = 278) receiving an abnormal screening test result a mean of 7 weeks earlier were assessed prior to a repeat screening test intended to clarify their previous abnormal result. Measures of disposition (optimism, informational coping style), social environment (social support and constraint), emotional processing, distress, and benefit finding were obtained. Regression analyses indicated greater distress was associated with greater social constraint and emotional processing and a monitoring coping style in women with a family history of OC. Distress was unrelated to social support. Greater benefit finding was associated with both greater social constraint and support and greater distress. The primacy of social constraint in accounting for both benefit finding and distress was noteworthy and warrants further research on the role of social constraint in adaptation to stressful events.

  19. Chemotherapy drug response in ovarian cancer cells strictly depends on a cathepsin D-Bax activation loop

    PubMed Central

    Castino, Roberta; Peracchio, Claudia; Salini, Alessandra; Nicotra, Giuseppina; Trincheri, Nicol F; Démoz, Marina; Valente, Guido; Isidoro, Ciro

    2009-01-01

    The ovarian cancer cell lines A2780 (wild-type p53) and NIHOVCAR3 (mutated p53) showed, respectively, sensitivity and resistance towards several chemotherapy drugs. We hypothesized that the two cell lines differ in their ability to activate the intrinsic death pathway and have, therefore, dissected the lysosome-mitochondrion signalling pathway by pharmacological inhibition or genetic manipulation of key regulators and executioners. Biochemical and morphological confocal fluorescence studies showed that: (1) In A2780 cells bcl-2 is expressed at an undetectable level, whereas Bax is expressed at a rather high level; by contrast, bcl-2 is highly expressed and Bax is expressed at extremely low levels in NIHOVCAR3 cells; (2) Chemotherapy treatment reduced the expression of bcl-2 in NIHOVCAR3 cells, yet these cells resisted to drug toxicity; (3) Cathepsin D (CD), not cathepsin B or L, mediates the activation of the mitochondrial intrinsic death pathway in A2780 cells; (4) Lysosome leakage and cytosolic relocation of CD occurs in the chemosensitive A2780 cells, not in the chemoresistant NIHOVCAR3 cells; (5) Bax is essential for the permeabilization of both lysosomes and mitochondria in A2780 cells exposed to chemotherapy drugs; (6) CD activity is mandatory for the oligomerization of Bax on both mitochondrial and lysosomal membranes; (7) Bax activation did not occur in the resistant NIHOVCAR3 cells despite their high content in CD. The present data are consistent with a model in which on treatment with a cytotoxic drug the activation of a CD-Bax loop leads to the generalized permeabilization of lysosomes and eventually of mitochondria, thus reaching the point of no return, and culminates with the activation of the caspase cascade. Our data also imply that dysfunctional permeabilization of lysosomes contributes to the development of chemoresistance. PMID:18657225

  20. Effects of acute unilateral ovariectomy to pre-pubertal rats on steroid hormones secretion and compensatory ovarian responses

    PubMed Central

    2011-01-01

    In the present study we analyzed the existence of asymmetry in the secretion of steroid hormones in pre-pubertal female rats treated with unilateral ovariectomy (ULO) or unilateral perforation of the abdominal wall (sham-surgery). Treated rats were sacrificed at different times after surgery. Since sham-surgery had an apparent effect on the age of first vaginal estrous (FVE) and serum levels hormone, the results of the sham surgery groups were used to assess the effects of their respective surgery treatment groups. On the day of FVE, compensatory ovulation (CO) and compensatory ovarian hypertrophy (COH) were similar in animals with ULO, regardless of the ovary remaining in situ. In ULO treated animals, progesterone (P4) levels were higher than in animals with sham-surgery one hour after treatment but lower in rats sacrificed at FEV. Left-ULO resulted in lower testosterone (T) concentration 48 and 72 hours after surgery. In rats with Right-ULO lower T concentrations were observed in rats sacrificed one or 72 hours after surgery, and at FVE. ULO (left or right) resulted in lower estradiol (E2) concentrations one or 72 hours after treatment. In rats with Left-ULO, E2 levels were higher 48 hours after surgery and at FVE. Left-ULO resulted in higher levels of follicle stimulating hormone (FSH) five hours after surgery and at FVE. FSH levels were higher in rats with Right-ULO sacrificed on FVE. The present results suggest that in the pre-pubertal rat both ovaries have similar capacities to secrete P4, and that the right ovary has a higher capacity to secrete E2. Taken together, the present results support the idea that the effects of ULO result from the decrease in glandular tissue and changes in the neural information arising from the ovary. PMID:21450102

  1. Ovarian and PGF2α responses to stimulation of endogenous PRL pulses during the estrous cycle in mares.

    PubMed

    Pinaffi, F L V; Khan, F A; Silva, L A; Beg, M A; Ginther, O J

    2012-10-01

    The effects of a PRL-stimulating substance (sulpiride) on PRL and PGF2α secretion and on luteal and ovarian follicular dynamics were studied during the estrous cycle in mares. A control group (n = 9) and a sulpiride group (Sp; n = 10) were used. Sulpiride (25 mg) was given every 8 h from Day 13 postovulation to the next ovulation. Repeated sulpiride treatment did not appear to maintain PRL concentrations at 12-h intervals beyond Day 14. Therefore, the hypothesis that a long-term increase in PRL altered luteal and follicular end points was not testable. Hourly samples were collected from the hour of a treatment (Hour 0) to Hour 8 on Day 14. Concentrations of PRL increased to maximum at Hour 4 in the Sp group. The PRL pulses were more prominent (P < 0.008) in the sulpiride group (peak, 19.4 ± 1.9 ng/mL; mean ± SEM) than in the controls (11.5 ± 1.8 ng/mL). Concentrations of a metabolite of PGF2α (PGFM), number, and characteristics of PGFM pulses, and concentrations of progesterone during Hours 0 to 8 were not affected by the increased PRL. A novel observation was that the peak of a PRL pulse occurred at the same hour or 1 h later than the peak of a PGFM pulse in 8 of 8 PGFM pulses in the controls and in 6 of 10 pulses in the Sp group (P < 0.04), indicating that sulpiride interfered with the synchrony between PGFM and PRL pulses. The hypothesis that sulpiride treatment during the equine estrous cycle increases concentrations of PRL and the prominence of PRL pulses was supported.

  2. Selection of suitable reference genes for gene expression studies in normal human ovarian tissues, borderline ovarian tumours and ovarian cancer.

    PubMed

    Ofinran, Olumide; Bose, Ujjal; Hay, Daniel; Abdul, Summi; Tufatelli, Cristina; Khan, Raheela

    2016-12-01

    The use of reference genes is the most common method of controlling the variation in mRNA expression during quantitative polymerase chain reaction, although the use of traditional reference genes, such as β‑actin, glyceraldehyde‑3‑phosphate dehydrogenase or 18S ribosomal RNA, without validation occasionally leads to unreliable results. Therefore, the present study aimed to evaluate a set of five commonly used reference genes to determine the most suitable for gene expression studies in normal ovarian tissues, borderline ovarian and ovarian cancer tissues. The expression stabilities of these genes were ranked using two gene stability algorithms, geNorm and NormFinder. Using geNorm, the two best reference genes in ovarian cancer were β‑glucuronidase and β‑actin. Hypoxanthine phosphoribosyltransferase‑1 and β‑glucuronidase were the most stable in ovarian borderline tumours, and hypoxanthine phosphoribosyltransferase‑1 and glyceraldehyde‑3‑phosphate dehydrogenase were the most stable in normal ovarian tissues. NormFinder ranked β‑actin the most stable in ovarian cancer, and the best combination of two genes was β‑glucuronidase and β‑actin. In borderline tumours, hypoxanthine phosphoribosyltransferase‑1 was identified as the most stable, and the best combination was hypoxanthine phosphoribosyltransferase‑1 and β‑glucuronidase. In normal ovarian tissues, β‑glucuronidase was recommended as the optimum reference gene, and the most optimum pair of reference genes was hypoxanthine phosphoribosyltransferase‑1 and β‑actin. To the best of our knowledge, this is the first study to investigate the selection of a set of reference genes for normalisation in quantitative polymerase chain reactions in different ovarian tissues, and therefore it is recommended that β‑glucuronidase, β‑actin and hypoxanthine phosphoribosyltransferase‑1 are the most suitable reference genes for such analyses.

  3. Borderline ovarian tumors: a review of treatment.

    PubMed Central

    Chambers, J. T.

    1989-01-01

    Borderline ovarian tumors have an excellent prognosis. In stage I disease, no therapy in addition to surgery is needed, and conservation of ovarian tissue for future childbearing may be appropriate. In advanced stages, the use of adjuvant therapy has not consistently led to cures, and complications have been reported. A randomized study of no adjuvant therapy versus adjuvant treatment with long-term follow-up will be necessary to determine the efficacy of additional treatment. PMID:2556863

  4. Functional Proteomics-Based Ovarian Cancer Biomarkers

    DTIC Science & Technology

    2010-11-01

    tissue , then incubating the samples at various time points to see the effect on RPPA –determined protein levels had already been done using breast tissue ...1985): 131. 27  Cao, Liyun, et al. " Tissue transglutaminase protects epithelial ovarian cancer cells from cisplatin-induced apoptosis by promoting...Dabholkar, Meenakshi, et al. "ERCC1 and ERCC2 expression in malignant tissues from ovarian cancer patients." Journal of the National Cancer Institute

  5. Effects of ovarian steroids upon responses mediated by adrenoceptors in separated layers of the myometrium and in the costo-uterine muscle of the guinea-pig

    PubMed Central

    Hartley, Margaret L.; Pennefather, Jocelyn N.; Story, Margot E.

    1983-01-01

    1 This study describes the effects of ovarian steroid hormones upon the responses to adrenoceptor agonists of isolated myometrium, separated into its longitudinal and circular layers, and of costo-uterine muscle from guinea-pigs. The preparations were field-stimulated at 100 s intervals, and the adrenoceptor agonists phenylephrine and isoprenaline produced enhancement or inhibition of the evoked contractions. 2 Isoprenaline produced propranolol-sensitive inhibitory effects in longitudinal and circular myometrium and costo-uterine muscle preparations from animals from all experimental groups: i.e. from nonsteroid-treated animals (ovariectomized and intact); intact animals treated with either oestrogen or progesterone alone; ovariectomized animals treated with oestrogen; ovariectomized and intact animals treated with progesterone following oestrogen priming; and from animals 1-4 days post-partum. Longitudinal myometrial preparations from progesterone-treated oestrogen-primed and from post-partum animals were most sensitive to this agonist. 3 Phenylephrine produced phentolamine-sensitive excitatory effects in circular myometrial and costo-uterine muscle preparations from animals from all the experimental groups. In contrast, propranolol-sensitive inhibitory responses to phenylephrine occurred in longitudinal myometrial preparations taken from animals treated with progesterone following oestrogen priming, and from post-partum animals. Longitudinal myometrium from animals from the remaining experimental groups exhibited phentolamine-sensitive excitatory responses to phenylephrine. 4 The basis for the selective effect upon the longitudinal myometrium of exposure to progesterone following a period of oestrogen priming, is discussed. The results described are consistent with the possibility that in the longitudinal layer of guinea-pig uterus exposed to progesterone following oestrogen priming there is an increase in the proportion of β-adrenoceptors in this layer. This

  6. Predictive and therapeutic markers in ovarian cancer

    DOEpatents

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

    2013-03-26

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

  7. Evaluation of DNA Repair Function as a Predictor of Response in a Clinical Trial of PARP Inhibitor Monotherapy for Recurrent Ovarian Carcinoma

    DTIC Science & Technology

    2014-10-01

    NCT01891344). 15. SUBJECT TERMS ovarian cancer, drug resistance, rucaparib, phase 2, DNA repair, homologous recombination , nonhomologous end- joining...words: ovarian cancer, drug resistance, rucaparib, phase 2, DNA repair, homologous recombination , nonhomologous end-joining (NHEJ), poly(ADP-ribose...REPORT DATE October2014 2. REPORT TYPE Annual Report 3. DATES COVERED 4. TITLE AND SUBTITLE Evaluation of DNA Repair Function as a Predictor

  8. The inherent cellular radiosensitivity of epithelial ovarian carcinoma

    SciTech Connect

    Rotmensch, J.; Schwartz, J.L.; Atcher, R.W.; Grdina, D.J.; Toohill, M.; Weichselbaum, R.W. )

    1989-12-01

    Ovarian carcinomas of similar histology have variable responses to radiation therapy. It has been suggested that inherent cellular resistance to radiation may in part underlie radiotherapy failure. To determine in vitro radiobiological parameters of papillary serous adenocarcinoma of the ovary, we investigated the cellular responses of 16 early-passage ovarian carcinoma cell lines to radiation. The radiosensitivity, as measured by D0, ranged from 1.05 to 2.40 Gy (mean 1.70 Gy), and, as measured by D, ranged from 1.65 to 3.54 Gy (mean 2.38 Gy). The extrapolation number -n ranged from 1.1 to 2.0 (mean 1.5). The cells had a 1.3- to 5.4-fold (mean 2.8) ability to recover from potential lethal damage (PLDR) 24 hr after irradiation and subculture from plateau-phase cultures. Their inherent radioresistance may be one factor in the failure of some ovarian cancers to be sterilized by radiation.

  9. Germline mutations of BRCA1 gene exon 11 are not associated with platinum response neither with survival advantage in patients with primary ovarian cancer: understanding the clinical importance of one of the biggest human exons. A study of the Tumor Bank Ovarian Cancer (TOC) Consortium.

    PubMed

    Dimitrova, Desislava; Ruscito, Ilary; Olek, Sven; Richter, Rolf; Hellwag, Alexander; Türbachova, Ivana; Woopen, Hannah; Baron, Udo; Braicu, Elena Ioana; Sehouli, Jalid

    2016-09-01

    Germline mutations in BRCA1 gene have been reported in up to 20 % of epithelial ovarian cancer (EOC) patients. Distinct clinical characteristics have been attributed to this special EOC population. We hypothesized that mutations in different BRCA1 gene exons may differently affect the clinical course of the disease. The aim of this study was to analyze, in a large cohort of primary EOCs, the clinical impact of mutations in BRCA1 gene exon 11, the largest exon of the gene sequence encoding the 60 % of BRCA1 protein. Two hundred sixty-three primary EOC patients, treated between 2000 and 2008 at Charité University Hospital of Berlin, were included. Patients' blood samples were obtained from the Tumor Ovarian Cancer (TOC) Network ( www.toc-network.de ). Direct sequencing of BRCA1 gene exon 11 was performed for each patient to detect mutations. Based on their BRCA1 exon 11 mutational status, patients were compared regarding clinico-pathological variables and survival. Mutations in BRCA1 exon 11 were found in 18 out of 263 patients (6.8 %). Further 10/263 (3.8 %) cases showed variants of uncertain significance (VUS). All exon 11 BRCA1-positive tumors (100 %) were Type 2 ovarian carcinomas (p = 0.05). Age at diagnosis was significantly younger in Type 2 exon 11 mutated patients (p = 0.01). On multivariate analysis, BRCA1 exon 11 mutational status was not found to be an independent predictive factor for optimal cytoreduction, platinum response, or survival. Mutations in BRCA1 gene exon 11 seem to predispose women to exclusively develop a Type 2 ovarian cancer at younger age. Exon 11 BRCA1-mutated EOC patients showed distinct clinico-pathological features but similar clinical outcome with respect to sporadic EOC patients.

  10. The Heat Shock Transcription Factor HSF1 Induces Ovarian Cancer Epithelial-Mesenchymal Transition in a 3D Spheroid Growth Model

    PubMed Central

    Aoisa, Candice; Menzie, Christopher J.; Ubaldini, Ashley

    2016-01-01

    Ovarian cancer is the most lethal gynecological cancer, with over 200,000 women diagnosed each year and over half of those cases leading to death. The proteotoxic stress-responsive transcription factor HSF1 is frequently overexpressed in a variety of cancers and is vital to cellular proliferation and invasion in some cancers. Upon analysis of various patient data sets, we find that HSF1 is frequently overexpressed in ovarian tumor samples. In order to determine the role of HSF1 in ovarian cancer, inducible HSF1 knockdown cell lines were created. Knockdown of HSF1 in SKOV3 and HEY ovarian cancer cell lines attenuates the epithelial-to-mesenchymal transition (EMT) in cells treated with TGFβ, as determined by western blot and quantitative RT-PCR analysis of multiple EMT markers. To further explore the role of HSF1 in ovarian cancer EMT, we cultured multicellular spheroids in a non-adherent environment to simulate early avascular tumors. In the spheroid model, cells more readily undergo EMT; however, EMT inhibition by HSF1 becomes more pronounced in the spheroid model. These findings suggest that HSF1 is important in the ovarian cancer TGFβ response and in EMT. PMID:27997575

  11. Neutrophil to lymphocyte ratio and platelet to lymphocyte ratio are predictive of chemotherapeutic response and prognosis in epithelial ovarian cancer patients treated with platinum-based chemotherapy.

    PubMed

    Miao, Yi; Yan, Qin; Li, Shuangdi; Li, Bilan; Feng, Youji

    2016-06-07

    The aim of present study was to investigate the role of preoperative neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) used as prognostic markers for predicting chemotherapeutic response and survival outcomes in patients with epithelial ovarian cancer (EOC) who are receiving platinum-based chemotherapy. A total of 344 patients diagnosed with EOC who are receiving platinum-based chemotherapy from 2005 to 2010 in the hospital were enrolled. NLR and PLR were calculated from complete blood cell count taken before operation. The patients were divided into platinum-resistant (P-R) group and platinum-sensitive (P-S) group according to chemotherapeutic response. Clinicopathologic variables and outcomes were retrospectively collected and compared among groups. We used receiver operating characteristic (ROC) curves to calculate optimal cut-off values for NLR and PLR to predict chemotherapeutic response and prognosis. The AUC, sensitivity, specificity of NLR > 3.02 to predict platinum resistance were 0.819, 75.0% and 81.45%, respectively. The corresponding values of PLR > 207 were 0.727, 60.42% and 85.48%, respectively. Patients with lower value of NLR (NLR < 3.02) or PLR (PLR < 207) had a longer progression-free survival (PFS) and overall survival (OS). In multivariate analysis, NLR and PLR showed a significant association with PFS (hazard ratio [HR], 1.733; 95%CI, 1.225-2.453, P = 0.002 and HR, 1.952; 95%CI, 1.430-2.662, P < 0.001) and OS (HR, 1.616; 95%CI, 1.138-2.297, P = 0.007, and HR, 2.167; 95%CI, 1.565-3.000, P < 0.001). These results suggest that the assessment of NLR and PLR could assist the identification of patients with poor prognosis and had potential clinical value in predicting platinum resistance in patients with EOC.

  12. Evaluation and therapy of polycystic ovarian syndrome.

    PubMed

    Loy, R; Seibel, M M

    1988-12-01

    The amenorrhea associated with bilateral polycystic ovaries, described by Stein and Leventhal, actually represents a syndrome involving various organs and systems. Clinically, this symptom complex commonly presents as menstrual disturbances, infertility, excessive body weight, and hirsutism. An understanding of the pathophysiology that underlies these symptoms provides a logical basis for evaluation and treatment of the syndrome. The diagnostic approach may involve biochemical determinations (baseline, stimulated, and suppressed) and radiologic testing. Therapy is directed at chronic anovulation, the hyperandrogenism responsible for hirsutism and acne, and the prophylaxis against endometrial and breast carcinomas. Ovulation can be induced with various agents, many of which have a risk of ovarian hyperstimulation in the PCOD patient. The use of GnRH agonists with HMG or FSH for ovulation induction will probably increase in the future. Although classic wedge resection has little place in modern management of PCOD, the recent laparoscopic ovarian cautery remains largely unstudied with respect to long-term postoperative plasma androgen levels and pelvic adhesions. It is too premature to evaluate this new surgical therapy. Hirsutism is effectively treated with estrogen-progestin combinations, medroxyprogesterone acetate, androgen receptor blockers (spironolactone, cimetidine, cyproterone acetate, and cyproheptadine), and glucocorticoids. To date, the available GnRH agonists have not been found selective enough to be used in the treatment of hirsutism, owing to possible long-term complications. Most medical approaches should include electrolysis for permanent hair removal. At present, gynecologic surgery seems to have little place in the management of hirsutism.

  13. Combination Chemotherapy and Peripheral Stem Cell Transplantation in Treating Patients With Stage III Ovarian Cancer

    ClinicalTrials.gov

    2016-03-17

    Malignant Ovarian Mixed Epithelial Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Primary Peritoneal Carcinoma; Stage III Ovarian Cancer; Undifferentiated Ovarian Carcinoma

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

    PubMed

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

    2014-09-01

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

  15. Expression of SDF-1 and CXCR4 transcript variants and CXCR7 in epithelial ovarian cancer.

    PubMed

    Jaszczynska-Nowinka, Karolina; Rucinski, Marcin; Ziolkowska, Agnieszka; Markowska, Anna; Malendowicz, Ludwik K

    2014-05-01

    Chemokine stromal cell-derived factor-1 (SDF-1) and its receptors, CXCR4 and CXCR7, have been implicated in epithelial ovarian cancer progression and metastasis. However, limited data are available on the expression levels of SDF-1 and CXCR4 variants and CXCR7 in human epithelial ovarian cancer. The present study aimed to characterize the expression pattern and levels of SDF-1, CXCR4 and CXCR7 in normal human ovaries and epithelial ovarian cancer. The expression of SDF-1 and CXCR4 transcript variants and CXCR7 was determined by quantitative polymerase chain reaction (qPCR). Plasma SDF-1α levels were determined by commercially available EIA kits and cancer antigen 125 (CA 125) levels were quantified by automated microparticle enzyme immunosorbent assay. High expression levels of SDF-1 transcript variant 1 were identified in ovarian cancer and control ovaries. By contrast, in both groups the expression levels of SDF-1 transcript variants 3 and 4 were extremely low. Furthermore, SDF-1 variant 1 levels were notably higher in epithelial ovarian cancer than in control ovaries, while data for the remaining transcripts were similar in both groups. CXCR4 transcript variant 2 and CXCR7 expression levels in normal and neoplastic ovaries were similar. In both groups, CXCR4 transcript variant 2 was not detected. Plasma SDF-1α levels were notably higher in females with epithelial ovarian cancer than in the control ovaries. Elevated levels of blood SDF-1α were found prior to surgery, 6 days after surgery and following completion of the first chemotherapy course. These increases were independent of the type of epithelial ovarian cancer. Our results suggest that the expression of SDF-1 and the genes controlling alternative splicing are elevated in epithelial ovarian cancer, leading to an increased formation of SDF-1 variant 1. Elevated plasma SDF-1α levels in epithelial ovarian cancer patients are not associated with the presence of tumors and/or metastases, however reflect a

  16. Antenatal Hypoxia Induces Programming of Reduced Arterial Blood Pressure Response in Female Rat Offspring: Role of Ovarian Function

    PubMed Central

    Xiao, DaLiao; Huang, Xiaohui; Xue, Qin; Zhang, Lubo

    2014-01-01

    In utero exposure to adverse environmental factors increases the risk of cardiovascular disease in adulthood. The present study tested the hypothesis that antenatal hypoxia causes a gender-dependent programming of altered arterial blood pressure response (BP) in adult offspring. Time-dated pregnant rats were divided into normoxic and hypoxic (10.5% O2 from days 15 to 21 of gestation) groups. The experiments were conducted in adult offspring. Antenatal hypoxia caused intrauterine growth restriction, and resulted in a gender-dependent increase Angiotensin II (Ang II)-induced BP response in male offspring, but significant decrease in BP response in female offspring. The baroreflex sensitivity was not significantly altered. Consistent with the reduced blood pressure response, antenatal hypoxia significantly decreased Ang II-induced arterial vasoconstriction in female offspring. Ovariectomy had no significant effect in control animals, but significantly increased Ang II-induced maximal BP response in prenatally hypoxic animals and eliminated the difference of BP response between the two groups. Estrogen replacement in ovariectomized animals significantly decreased the BP response to angiotensin II I only in control, but not in hypoxic animals. The result suggests complex programming mechanisms of antenatal hypoxia in regulation of ovary function. Hypoxia-mediated ovary dysfunction results in the phenotype of reduced vascular contractility and BP response in female adult offspring. PMID:24905716

  17. Molecular profiles and pathogen-induced transcriptional responses of prawn B cell lymphoma-2 related ovarian killer protein (BOK).

    PubMed

    Chaurasia, Mukesh Kumar; Palanisamy, Rajesh; Harikrishnan, Ramasamy; Arasu, Mariadhas Valan; Al-Dhabi, Naif Abdullah; Arockiaraj, Jesu

    2015-08-01

    In this study, we have reported a molecular characterization of the first B cell lymphoma-2 (BCL-2) related ovarian killer protein (BOK) from freshwater prawn Macrobrachium rosenbergii (Mr). BOK is a novel pro-apoptotic protein of the BCL-2 family that entails in mediating apoptosis to remove cancer cells. A cDNA sequence of MrBOK was identified from the prawn cDNA library and its full length was obtained by internal sequencing. The coding region of MrBOK yields a polypeptide of 291 amino acids. The analysis revealed that MrBOK contains a transmembrane helix at V(261)-L(283) and a putative BCL-2 family domain at V(144)-W(245). MrBOK also possessed four putative BCL-2 homology domains including BH1, BH2, BH3 and weak BH4. The BH3 contains 21 binding sites and among them five residues are highly conserved with the aligned BOK proteins. The homology analysis showed that MrBOK shared maximum similarity with the Caligus rogercresseyi BOK A. The topology of the phylogenetic tree was classified into nine sister groups which includes BOK, BAK, BAX, BAD, BCL-2, BCL-XL, NR13 and MCL members. The BOK protein group further sub-grouped into vertebrate and invertebrate BOK, wherein MrBOK located within insect monophyletic clad of invertebrate BOK. The secondary structural analysis showed that MrBOK contains 11 α-helices (52.2%) which are connected over random coils (47.7%). The 3D structure of MrBOK showed three central helices (α6, α7 and α8) which formed the core of the protein and are flanked on one side by α1, α2 and α3, and on the other side by α4, α5 and α11. MrBOK mRNA is expressed most abundantly (P < 0.05) in ovary compared to other tissues taken for analysis. Hence ovary was selected to study the possible roles of MrBOK mRNA regulation upon bacterial (Aeromonas hydrophila and Vibrio harveyi) and viral [white spot syndrome virus (WSSV) and M. rosenbergii nodovirus] infection. During bacterial and viral infection, the highest MrBOK mRNA transcription was varied

  18. Erlotinib Plus Carboplatin and Paclitaxel in Ovarian Carcinoma

    ClinicalTrials.gov

    2015-10-29

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

  19. Identification of anti-CA125 antibody responses in ovarian cancer patients by a novel deep sequence-coupled biopanning platform

    PubMed Central

    Frietze, Kathryn M.; Roden, Richard B.S.; Lee, Ji-Hyun; Shi, Yang; Peabody, David S.; Chackerian, Bryce

    2015-01-01

    High-grade epithelial ovarian cancer (OvCa) kills more women than any other gynecologic cancer and is rarely diagnosed at an early stage. We sought to identify tumor-associated antigens (TAA) as candidate diagnostic and/or immunotherapeutic targets by taking advantage of tumor autoantibody responses in individuals with OvCa. Plasma-derived IgG from a pool of five patients with advanced OvCa was subjected to iterative biopanning using a library of bacteriophage MS2 virus-like particles (MS2-VLPs) displaying diverse short random peptides. After two rounds of biopanning, we analyzed the selectant population of MS2-VLPs by Ion Torrent deep-sequencing. One of the top 25 most abundant peptides identified (DISGTNTSRA) had sequence similarity to cancer antigen 125 (CA125/MUC16), a well-known OvCa-associated antigen. Mice immunized with MS2-DISGTNTSRA generated antibodies that cross-reacted with purified soluble CA125 from OvCa cells but not membrane-bound CA125, indicating that the DISGTNTSRA peptide was a CA125/MUC16 peptide mimic of soluble CA125. Pre-operative OvCa patient plasma (n = 100) was assessed for anti-DISGTNTSRA, anti-CA125, and CA125. Patients with normal CA125 (< 35 IU/mL) at time of diagnosis had significantly more antibodies to DISGTNTSRA and to CA125 than those patients who had high CA125 (> 35 IU/mL). A statistically significant survival advantage was observed for patients who had either normal CA125 and/or higher concentrations of antibodies to CA125 at time of diagnosis. These data show the feasibility of using deep sequence-coupled biopanning to identify TAA autoantibody responses from cancer patient plasma and suggest a possible antibody-mediated mechanism for low CA125 plasma concentrations in some OvCa patients. PMID:26589767

  20. Executive impairment determines ADHD medication response: implications for academic achievement.

    PubMed

    Hale, James B; Reddy, Linda A; Semrud-Clikeman, Margaret; Hain, Lisa A; Whitaker, James; Morley, Jessica; Lawrence, Kyle; Smith, Alex; Jones, Nicole

    2011-01-01

    Methylphenidate (MPH) often ameliorates attention-deficit/hyperactivity disorder (ADHD) behavioral dysfunction according to indirect informant reports and rating scales. The standard of care behavioral MPH titration approach seldom includes direct neuropsychological or academic assessment data to determine treatment efficacy. Documenting "cool" executive-working memory (EWM) and "hot" self-regulation (SR) neuropsychological impairments could aid in differential diagnosis of ADHD subtypes and determining cognitive and academic MPH response. In this study, children aged 6 to 16 with ADHD inattentive type (IT; n = 19) and combined type (n = 33)/hyperactive-impulsive type (n = 4) (CT) participated in double-blind placebo-controlled MPH trials with baseline and randomized placebo, low MPH dose, and high MPH dose conditions. EWM/ SR measures and behavior ratings/classroom observations were rank ordered separately across conditions, with nonparametric randomization tests conducted to determine individual MPH response. Participants were subsequently grouped according to their level of cool EWM and hot SR circuit dysfunction. Robust cognitive and behavioral MPH response was achieved for children with significant baseline EWM/SR impairment, yet response was poor for those with adequate EWM/ SR baseline performance. Even for strong MPH responders, the best dose for neuropsychological functioning was typically lower than the best dose for behavior. Findings offer one possible explanation for why long-term academic MPH treatment gains in ADHD have not been realized. Implications for academic achievement and medication titration practices for children with behaviorally diagnosed ADHD will be discussed.

  1. Optimized Prediction of Extreme Treatment Outcomes in Ovarian Cancer

    PubMed Central

    Misganaw, Burook; Ahsen, Eren; Singh, Nitin; Baggerly, Keith A.; Unruh, Anna; White, Michael A.; Vidyasagar, M.

    2015-01-01

    Ovarian cancer is the fifth leading cause of death among female cancers. Front-line therapy for ovarian cancer is platinum-based chemotherapy. However, the response of patients is highly nonuniform. The TCGA database of serous ovarian carcinomas shows that ~10% of patients respond poorly to platinum-based chemotherapy, with tumors relapsing in seven months or less. Another 10% or so enjoy disease-free survival of three years or more. The objective of the present research is to identify a small number of highly predictive biomarkers that can distinguish between the two extreme responders and then extrapolate to all patients. This is achieved using the lone star algorithm that is specifically developed for biological applications. Using this algorithm, we are able to identify biomarker panels of 25 genes (of 12,000 genes) that can be used to classify patients into one of the three groups: super responders, medium responders, and nonresponders. We are also able to determine a discriminant function that can divide the entire patient population into two classes, such that one group has a clear survival advantage over the other. These biomarkers are developed using the TCGA Agilent platform data and cross-validated on the TCGA Affymetrix platform data, as well as entirely independent data from Tothill et al. The P-values on the training data are extremely small, sometimes below machine zero, while the P-values on cross-validation are well below the widely accepted threshold of 0.05. PMID:27034613

  2. Ovarian Cancer Stage IV

    MedlinePlus

    ... hyphen, e.g. -historical Searches are case-insensitive Ovarian Cancer Stage IV Add to My Pictures View /Download : ... 1200x1335 View Download Large: 2400x2670 View Download Title: Ovarian Cancer Stage IV Description: Drawing of stage IV shows ...

  3. Symptoms of Ovarian Cancer

    MedlinePlus

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

  4. Ovarian Cancer Stage IIIC

    MedlinePlus

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

  5. Premature ovarian failure.

    PubMed

    Kalantaridou, S N; Davis, S R; Nelson, L M

    1998-12-01

    In 1% of women, premature ovarian failure develops by 40 years of age, a condition causing amenorrhea, infertility, sex steroid deficiency, and elevated gonadotropins. Early loss of ovarian function has significant psychosocial sequelae and major health implications. These young women have a nearly two-fold age-specific increase in mortality rate. Among women with spontaneous premature ovarian failure who have a normal karyotype, half have ovarian follicles remaining in the ovary that function intermittently. Indeed, pregnancies have occurred after the diagnosis of premature ovarian failure. Thus, premature ovarian failure should not be considered as a premature menopause. Young women with this disorder have a 5% to 10% chance for spontaneous pregnancy. Attempts at ovulation induction using various regimens fail to induce ovulation rates greater than those seen in untreated patients; however, oocyte donation for women desiring fertility is an option. Young women with premature ovarian failure need a thorough assessment, sex steroid replacement, and long-term surveillance to monitor therapy. Estrogen-progestin replacement therapy should be instituted as soon as the diagnosis is made. Androgen replacement should also be considered for women with low libido, persistent fatigue, and poor well-being despite taking adequate estrogen replacement. Women with premature ovarian failure should be followed up for the presence of associated autoimmune endocrine disorders such as hypothyroidism, adrenal insufficiency, and diabetes mellitus.

  6. Response to Intervention for English Learners: Examining Models for Determining Response and Nonresponse

    ERIC Educational Resources Information Center

    Richards-Tutor, Catherine; Solari, Emily J.; Leafstedt, Jill M.; Gerber, Michael M.; Filippini, Alexis; Aceves, Terese C.

    2013-01-01

    Using extant data, the purpose of this study is to examine methods for determining response to intervention (RTI) in a sample of kindergarten English Learners (ELs). Three commonly used methods for determining RTI--(a) benchmark criteria, (b) slope discrepancy, and (c) dual discrepancy--are investigated. Participants included 117 ELs. Students…

  7. Genetics of the ovarian reserve

    PubMed Central

    Pelosi, Emanuele; Forabosco, Antonino; Schlessinger, David

    2015-01-01

    Primordial follicles or non-growing follicles (NGFs) are the functional unit of reproduction, each comprising a single germ cell surrounded by supporting somatic cells. NGFs constitute the ovarian reserve (OR), prerequisite for germ cell ovulation and the continuation of the species. The dynamics of the reserve is determined by the number of NGFs formed and their complex subsequent fates. During the reproductive lifespan, the OR progressively diminishes due to follicle atresia as well as recruitment, maturation, and ovulation. The depletion of the OR is the major determining driver of menopause, which ensues when the number of primordial follicles falls below a threshold of ∼1,000. Therefore, genes and processes involved in follicle dynamics are particularly important to understand the process of menopause, both in the typical reproductive lifespan and in conditions like primary ovarian insufficiency, defined as menopause before age 40. Genes and their variants that affect the timing of menopause thereby provide candidates for diagnosis of and intervention in problems of reproductive lifespan. We review the current knowledge of processes and genes involved in the development of the OR and in the dynamics of ovarian follicles. PMID:26528328

  8. Determination Method of Bridge Rotation Angle Response Using MEMS IMU.

    PubMed

    Sekiya, Hidehiko; Kinomoto, Takeshi; Miki, Chitoshi

    2016-11-09

    To implement steel bridge maintenance, especially that related to fatigue damage, it is important to monitor bridge deformations under traffic conditions. Bridges deform and rotate differently under traffic load conditions because their structures differ in terms of length and flexibility. Such monitoring enables the identification of the cause of stress concentrations that cause fatigue damage and the proposal of appropriate countermeasures. However, although bridge deformation monitoring requires observations of bridge angle response as well as the bridge displacement response, measuring the rotation angle response of a bridge subject to traffic loads is difficult. Theoretically, the rotation angle response can be calculated by integrating the angular velocity, but for field measurements of actual in-service bridges, estimating the necessary boundary conditions would be difficult due to traffic-induced vibration. To solve the problem, this paper proposes a method for determining the rotation angle response of an in-service bridge from its angular velocity, as measured by a inertial measurement unit (IMU). To verify our proposed method, field measurements were conducted using nine micro-electrical mechanical systems (MEMS) IMUs and two contact displacement gauges. The results showed that our proposed method provided high accuracy when compared to the reference responses calculated by the contact displacement gauges.

  9. Determination Method of Bridge Rotation Angle Response Using MEMS IMU

    PubMed Central

    Sekiya, Hidehiko; Kinomoto, Takeshi; Miki, Chitoshi

    2016-01-01

    To implement steel bridge maintenance, especially that related to fatigue damage, it is important to monitor bridge deformations under traffic conditions. Bridges deform and rotate differently under traffic load conditions because their structures differ in terms of length and flexibility. Such monitoring enables the identification of the cause of stress concentrations that cause fatigue damage and the proposal of appropriate countermeasures. However, although bridge deformation monitoring requires observations of bridge angle response as well as the bridge displacement response, measuring the rotation angle response of a bridge subject to traffic loads is difficult. Theoretically, the rotation angle response can be calculated by integrating the angular velocity, but for field measurements of actual in-service bridges, estimating the necessary boundary conditions would be difficult due to traffic-induced vibration. To solve the problem, this paper proposes a method for determining the rotation angle response of an in-service bridge from its angular velocity, as measured by a inertial measurement unit (IMU). To verify our proposed method, field measurements were conducted using nine micro-electrical mechanical systems (MEMS) IMUs and two contact displacement gauges. The results showed that our proposed method provided high accuracy when compared to the reference responses calculated by the contact displacement gauges. PMID:27834871

  10. Autoimmune premature ovarian failure

    PubMed Central

    2017-01-01

    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. PMID:28250725

  11. Satellite Aerodynamics and Density Determination from Satellite Dynamic Response

    NASA Technical Reports Server (NTRS)

    Karr, G. R.

    1972-01-01

    The aerodynamic drag and lift properties of a satellite are first expressed as a function of two parameters associated with gas-surface interaction at the satellite surface. The dynamic response of the satellite as it passes through the atmosphere is then expressed as a function of the two gas-surface interaction parameters, the atmospheric density, the satellite velocity, and the satellite orientation to the high speed flow. By proper correlation of the observed dynamic response with the changing angle of attack of the satellite, it is found that the two unknown gas-surface interaction parameters can be determined. Once the gas-surface interaction parameters are known, the aerodynamic properties of the satellite at all angles of attack are also determined.

  12. Rapidly-progressive catatonia responsive to zolpidem in a patient with ovarian teratoma-associated paraneoplastic encephalitis.

    PubMed

    Amorim, Edilberto; McDade, Eric M

    2016-08-01

    Psychiatric symptoms and catatonia are key components of the clinical presentation of paraneoplastic encephalitis; additionally symptoms can be long-lasting and often difficult to treat. We report a 73-year-old patient with rapidly progressive catatonia not responsive to immunotherapy, tumor resection, electroconvulsive therapy, or benzodiazepines who had significant improvement after zolpidem administration. This report suggests that zolpidem is an option in the treatment of patients with refractory catatonia and paraneoplastic encephalitis.

  13. Determination of the full response function of personal neutron dosemeters.

    PubMed

    Reginatto, M; Luszik-Bhadra, M

    2007-01-01

    The response of neutron dosemeters may be determined directly from measurements, provided a sufficiently large number of measurements in monoenergetic neutron fields covering the entire energy range of interest is available. In practice this is not feasible due to the lack of monoenergetic neutron fields in the thermal and intermediate energy region (i.e. energies<24 keV). To deal with this difficulty, we have developed a method which can take into account additional information about the response of the dosemeter. Our analysis makes use of two types of data, measurements made using monoenergetic neutron beams and measurements made in neutron fields with broad energy distributions. The dosemeter responses are described using a parametrised model, based on a minimum of assumptions: that they should fit the data within experimental uncertainties, and that they should remain close to a simple interpolation of the monoenergetic and thermal neutron field data.

  14. B lymphocyte immune response gene phenotype is genetically determined

    SciTech Connect

    Tse, H.Y.; Mond, J.J.; Longo, D.L.

    1982-04-01

    We examined the effects of the developmental milieu on the capacity of B cells to undergo immune response gene-controlled, T cell-dependent polyclonal proliferation. Although I-Aq poly(Glu60 Ala30 Tyr10)n (GAT)-nonresponder T cells developing in a responder environment become phenotypic GAT-responders, I-Aq B cells remain unresponsive to GAT, even after maturation in a GAT-responder animal. Conversely, (B10.A x B10.Q)F1 ((GAT responder x GAT nonresponder)F1) T cells developing in a B10.Q GAT nonresponder host fail to respond to GAT, but F1 B cells from the same F1 leads to parent chimeras make excellent proliferative responses in the presence of GAT and responder T cells. Thus, by this assay, B cell immune response gene function is genetically determined and is not affected by the developmental milieu.

  15. A high response to controlled ovarian stimulation induces premature luteinization with a negative impact on pregnancy outcomes in a gonadotropin-releasing hormone antagonist cycle

    PubMed Central

    Koo, Hwa Seon; Cha, Sun Hwa; Kim, Hye Ok; Song, In Ok; Min, Eung Gi; Yang, Kwang Moon

    2015-01-01

    Objective The goal of this study was to investigate the relationship between serum progesterone (P4) levels on the day of human chorionic gonadotropin (hCG) administration and the pregnancy rate among women undergoing controlled ovarian stimulation for in vitro fertilization (IVF) or intracytoplasmic sperm injection-embryo transfer (ICSI-ET) using a flexible antagonist protocol. Methods This prospective study included 200 IVF and ICSI-ET cycles in which a flexible antagonist protocol was used. The patients were divided into five distinct groups according to their serum P4 levels at the time of hCG administration (0.80, 0.85, 0.90, 0.95, and 1.00 ng/mL). The clinical pregnancy rate (CPR) was calculated for each P4 interval. Statistically significant differences were observed at a serum P4 level of 0.9 ng/mL. These data suggest that a serum P4 concentration of 0.9 ng/mL may represent the optimal threshold level for defining premature luteinization (PL) based on the presence of a significant negative impact on the CPR. Results The CPR for each round of ET was significantly lower in the PL group defined using this threshold (25.8% vs. 41.8%; p=0.019), and the number of oocytes retrieved was significantly higher than in the non-PL group (17.3±7.2 vs. 11.0±7.2; p=0.001). Elevated serum P4 levels on the day of hCG administration were associated with a reduced CPR, despite the retrieval of many oocytes. Conclusion Measuring serum P4 values at the time of hCG administration is necessary in order to determine the optimal strategy for embryo transfer. PMID:26816874

  16. DIFFERENTIAL REGULATION OF THE BUMETANIDE-SENSITIVE COTRANSPORTER (NKCC2) BY OVARIAN HORMONES

    PubMed Central

    Musselman, Teddy M; Zhang, Zheng; Masilamani, Shyama ME

    2010-01-01

    The Na-K-2Cl cotransporter (NKCC2) regulates sodium transport along the thick ascending limb of Henle’s loop and is important in control of sodium balance, renal concentrating ability and renin release. To determine if there are sex differences in NKCC2 abundance and/or distribution, and to evaluate the contribution of ovarian hormones to any such differences, we performed semiquantitative immunoblotting and immunoperoxidase immunohistochemistry for NKCC2 in the kidney of Sprague Dawley male, female and ovariectomized (OVX) rats with and without 17-β estradiol or progesterone supplementation. Intact females demonstrated greater NKCC2 protein in homogenates of whole kidney (334%±29), cortex (219%±20) and outer medulla (133%±9) compared to males. Ovarian hormone supplementation to OVX rats regulated NKCC2 in the outer medulla only, with NKCC2 protein abundance decreasing slightly in response to progesterone but increasing in response to 17-β estradiol. Immunohistochemistry demonstrated prominent NKCC2 labeling in the apical membrane of thick ascending limb cells. Kidney section NKCC2 labeling confirmed regionalized regulation of NKCC2 by ovarian hormones. Localized regulation of NKCC2 by ovarian hormones may have importance in controlling sodium and water balance over the lifetime of women as the milieu of sex hormones varies. PMID:20580730

  17. Exploratory Analysis of TP53 Mutations in Circulating Tumour DNA as Biomarkers of Treatment Response for Patients with Relapsed High-Grade Serous Ovarian Carcinoma: A Retrospective Study

    PubMed Central

    Piskorz, Anna M.; Biggs, Heather; Addley, Helen; Freeman, Sue; Moyle, Penelope; Sala, Evis; Sayal, Karen; Hosking, Karen; Gounaris, Ioannis; Earl, Helena M.; Rosenfeld, Nitzan; Brenton, James D.

    2016-01-01

    Background Circulating tumour DNA (ctDNA) carrying tumour-specific sequence alterations may provide a minimally invasive means to dynamically assess tumour burden and response to treatment in cancer patients. Somatic TP53 mutations are a defining feature of high-grade serous ovarian carcinoma (HGSOC). We tested whether these mutations could be used as personalised markers to monitor tumour burden and early changes as a predictor of response and time to progression (TTP). Methods and Findings We performed a retrospective analysis of serial plasma samples collected during routine clinical visits from 40 patients with HGSOC undergoing heterogeneous standard of care treatment. Patient-specific TP53 assays were developed for 31 unique mutations identified in formalin-fixed paraffin-embedded tumour DNA from these patients. These assays were used to quantify ctDNA in 318 plasma samples using microfluidic digital PCR. The TP53 mutant allele fraction (TP53MAF) was compared to serum CA-125, the current gold-standard response marker for HGSOC in blood, as well as to disease volume on computed tomography scans by volumetric analysis. Changes after one cycle of treatment were compared with TTP. The median TP53MAF prior to treatment in 51 relapsed treatment courses was 8% (interquartile range [IQR] 1.2%–22%) compared to 0.7% (IQR 0.3%–2.0%) for seven untreated newly diagnosed stage IIIC/IV patients. TP53MAF correlated with volumetric measurements (Pearson r = 0.59, p < 0.001), and this correlation improved when patients with ascites were excluded (r = 0.82). The ratio of TP53MAF to volume of disease was higher in relapsed patients (0.04% per cm3) than in untreated patients (0.0008% per cm3, p = 0.004). In nearly all relapsed patients with disease volume > 32 cm3, ctDNA was detected at ≥20 amplifiable copies per millilitre of plasma. In 49 treatment courses for relapsed disease, pre-treatment TP53MAF concentration, but not CA-125, was associated with TTP. Response to

  18. Polyglutamate Paclitaxel and Carboplatin in Treating Patients With Ovarian Epithelial, Peritoneal, or Fallopian Tube Cancer

    ClinicalTrials.gov

    2015-05-07

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

  19. MV-NIS Infected Mesenchymal Stem Cells in Treating Patients With Recurrent Ovarian Cancer

    ClinicalTrials.gov

    2017-03-14

    Malignant Ovarian Brenner Tumor; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Ovarian Carcinoma

  20. Identification of a Genomic Signature Predicting for Recurrence in Early Stage Ovarian Cancer

    DTIC Science & Technology

    2013-10-01

    25 Patient information sheet You have previously been treated for early ovarian cancer at the Radium ...patients receiving chemotherapy does not need it. At the Radium Hospital we use a method with determination of the amount of DNA to identify patients...names. This code list will be kept at the Radium Hospital and only staff personnel responsible for this study will have access. All analyses will be

  1. The DNA damage mark pH2AX differentiates the cytotoxic effects of small molecule HDAC inhibitors in ovarian cancer cells.

    PubMed

    Wilson, Andrew J; Holson, Edward; Wagner, Florence; Zhang, Yan-Ling; Fass, Daniel M; Haggarty, Stephen J; Bhaskara, Srividya; Hiebert, Scott W; Schreiber, Stuart L; Khabele, Dineo

    2011-09-15

    High grade epithelial ovarian cancers are relatively sensitive to DNA damaging platinum-based chemotherapy, suggesting that the dependencies of ovarian tumors on DNA damage response pathways can be harnessed for therapeutic purposes. Our goal was to determine if the DNA damage mark gamma-H2AX phosphorylation (pH2AX) could be used to identify suitable cytotoxic histone deacetylase inhibitors (HDACi) for ovarian cancer treatment. Nineteen chemically diverse HDACi compounds were tested in 7 ovarian cancer cell lines. Fluorescent, biochemical and cell-based assays were performed to assess DNA damage by induction of pH2AX and to measure cell viability and apoptosis. The relationships between pH2AX and the cellular effects of cell viability and apoptosis were calculated. Selected HDACi were tested in combination with cisplatin and other DNA damaging agents to determine if the HDACi improved upon the effects of the DNA damaging agents. The HDACi compounds induced differing levels of pH2AX expression. High levels of pH2AX in HDACi-treated ovarian cancer cells were tightly associated with decreased cell viability and increased apoptosis. Consequently, a ketone-based HDACi was chosen and found to enhance the effects of cisplatin, even in ovarian cancer cells with extreme resistance to DNA damaging drugs. In conclusion, a fluorescent-based assay for pH2AX can be used to determine cellular responses to HDACi in vitro and may be a useful tool to identify potentially more effective HDACi for the treatment of ovarian cancer. In addition, these results lend support to the inclusion of ketone-derived HDACi compounds for future development.

  2. Technique for Determining Bridge Displacement Response Using MEMS Accelerometers

    PubMed Central

    Sekiya, Hidehiko; Kimura, Kentaro; Miki, Chitoshi

    2016-01-01

    In bridge maintenance, particularly with regard to fatigue damage in steel bridges, it is important to determine the displacement response of the entire bridge under a live load as well as that of each member. Knowing the displacement response enables the identification of dynamic deformations that can cause stresses and ultimately lead to damage and thus also allows the undertaking of appropriate countermeasures. In theory, the displacement response can be calculated from the double integration of the measured acceleration. However, data measured by an accelerometer include measurement errors caused by the limitations of the analog-to-digital conversion process and sensor noise. These errors distort the double integration results. Furthermore, as bridges in service are constantly vibrating because of passing vehicles, estimating the boundary conditions for the numerical integration is difficult. To address these problems, this paper proposes a method for determining the displacement of a bridge in service from its acceleration based on its free vibration. To verify the effectiveness of the proposed method, field measurements were conducted using nine different accelerometers. Based on the results of these measurements, the proposed method was found to be highly accurate in comparison with the reference displacement obtained using a contact displacement gauge. PMID:26907287

  3. Cardiovascular response to noise in type A and type B female subjects: Effect of the ovarian cycle

    NASA Astrophysics Data System (ADS)

    Di Nisi, J.; Muzet, A.

    1989-10-01

    The aim of the investigation was to study the heart rate and finger pulse responses during the menstrual cycle in type A and type B female subjects. Nine type A's and nine type B's were selected by using the French version of Bortner's short rating scale questionnaire. They were exposed to noise in three different periods of the menstrual cycle; menses (day 0-2), pre-ovulation (8-10) and post-ovulation (22-24). No significant difference in tonic heart rate level between type A's and type B's was found. The percentages of HRR and FPR were not significantly different for the two types of subjects. However, the amplitude of HRR and FPR were significantly higher in type A's than in type B's. significant differences related to the periods of the menstrual cycle were also found. In type B's, the amplitude of HRR was larger during menses than during the two other periods. In type A's, the amplitude of the FPR was higher during the menses than during the pre-ovulation. The percentage of noise stimuli eliciting HRR and FPR did not vary as a function of the menstrual cycle. These results are discussed in terms of excitability and balance of the autonomic nervous system.

  4. The Role and Application of Sirtuins and mTOR Signaling in the Control of Ovarian Functions

    PubMed Central

    Sirotkin, Alexander V.

    2016-01-01

    The present short review demonstrates the involvement of sirtuins (SIRTs) in the control of ovarian functions at various regulatory levels. External and endocrine factors can affect female reproduction via SIRTs-mammalian target of rapamycin (mTOR) system, which, via hormones and growth factors, can in turn regulate basic ovarian functions (proliferation, apoptosis, secretory activity of ovarian cells, their response to upstream hormonal regulators, ovarian folliculo- and oogenesis, and fecundity). SIRTs and SIRTs-related signaling molecules and drugs regulating mTOR can be used for characterization, prediction, and regulation of ovarian functions, as well as for diagnostics and treatment of ovarian disorders. PMID:27886120

  5. Reflex modulation of ovarian estradiol secretion by noxious mechanical stimulation of a hindpaw in anesthetized rats.

    PubMed

    Uchida, Sae; Kagitani, Fusako; Hotta, Harumi

    2012-11-02

    Previously, we demonstrated that electrical stimulation of the superior ovarian nerve in rats reduces the ovarian estradiol secretion rate. In the present study, we examined the effect of noxious mechanical afferent stimulation (pinching) of a hindpaw on the ovarian estradiol secretion rate in rats. The rats were anesthetized on the day of estrus, and the ovarian venous blood was collected intermittently. The secretion rate of estradiol from the ovary was calculated from differences in the estradiol concentration between ovarian venous plasma and systemic arterial blood plasma, and from the flow rate of ovarian venous plasma. Pinching stimulation of a hindpaw for 5 min decreased the estradiol secretion rate from the ovary. A significant reduction of the estradiol secretion rate began at 5 min after the end of the stimulation and lasted for 20 min. The minimum decrease in estradiol secretion rate was 71.1 ± 14.0% of the prestimulus basal values at 15 min after the stimulation ended. The decrease responses of the ovarian estradiol secretion rate were abolished by bilateral severance of the superior ovarian nerves. The efferent activity of the superior ovarian nerves was increased following hindpaw pinching. After spinal transection at the second cervical level, the increased response of the superior ovarian nerve activity by hindpaw pinching was abolished. These results indicate that noxious mechanical stimulation of a hindpaw decreases the estradiol secretion rate from the ovary, and that the response is due to reflex activation of ovarian sympathetic nerves, mediated by supraspinal structures.

  6. Inhibition of ovarian cancer cell proliferation by a cell cycle inhibitory peptide fused to a thermally responsive polypeptide carrier

    PubMed Central

    Massodi, Iqbal; Moktan, Shama; Rawat, Aruna; Bidwell, Gene L.; Raucher, Drazen

    2009-01-01

    Current treatment of solid tumors is limited by normal tissue tolerance, resulting in a narrow therapeutic index. To increase drug specificity and efficacy and to reduce toxicity in normal tissues, we have developed a polypeptide carrier for a cell cycle inhibitory peptide, which has the potential to be thermally targeted to the tumor site. The design of this polypeptide is based on elastin-like polypeptide (ELP). The coding sequence of ELP was modified by the addition of the cell penetrating peptide Bac-7 at the N-terminus and a 23 amino acid peptide derived from p21 at the C-terminus (Bac-ELP1-p21). Bac-ELP1-p21 is soluble in aqueous solutions below physiological temperature (37°C) but aggregates when the temperature is raised above 39°C, making it a promising thermally responsive therapeutic carrier that may be actively targeted to solid tumors by application of focused hyperthermia. While Bac-ELP1-p21 at 37°C did not have any effect on SKOV-3 cell proliferation, the use of hyperthermia increased the antiproliferative effect of Bac-ELP1-p21 compared with a thermally unresponsive control polypeptide. Bac-ELP1-p21 displayed both a cytoplasmic and nuclear distribution in the SKOV-3 cells, with nuclear-localized polypeptide enriched in the heated cells, as revealed by confocal microscopy. Using Western blotting, we show that Bac-ELP1-p21 caused a decrease in Rb phosphorylation levels in cells treated at 42°C. The polypeptide also induced caspase activation, PARP cleavage, and cell cycle arrest in S-phase and G2/M-phase. These studies indicate that ELP is a promising macromolecular carrier for the delivery of cell cycle inhibitory peptides to solid tumors. PMID:19588502

  7. Can Ovarian Cancer Be Found Early?

    MedlinePlus

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

  8. Characterization of bovine early growth response factor-1 and its gonadotropin-dependent regulation in ovarian follicles prior to ovulation.

    PubMed

    Sayasith, Khampoune; Brown, Kristy A; Lussier, Jacques G; Doré, Monique; Sirois, Jean

    2006-10-01

    Early growth response factor-1 (EGR-1) is a transcription factor that is involved in the transactivation of several genes. The objective of this study was to characterize gonadotropin-dependent regulation of bovine EGR-1 in preovulatory follicles prior to ovulation. Bovine EGR-1 cDNA was obtained by RT-PCR, 5'- and 3'-RACE, its open reading frame composed of 1623 bp, and its coding region encodes a 540-amino acid protein that displays 62-93% identity to known mammalian homologs. The regulation of EGR-1 mRNA was studied in bovine preovulatory follicles which were isolated 0-24 h post-hCG using semiquantitative RT-PCR/Southern blot. Results revealed that the levels of EGR-1 mRNA were very low in follicles at 0 h, markedly increased at 6 h (P < 0.05) when compared to 0 h, and decreased between 12 and 24 h post-hCG. High levels of the EGR-1 mRNA were also observed in corpus luteum, uterus, kidney, pituitary, and spleen, moderate and low in other bovine tissues tested. Analyses performed on isolated preparations of granulosa and theca cells indicated that EGR-1 mRNA was regulated in both cell types, with a predominant expression in granulosa cells. Immunohistochemistry on sections of preovulatory follicles isolated before and after hCG confirmed its protein expression in granulosa cells, 24 h post-hCG. Studies of EGR-1 regulation in primary granulosa cells cultured with forskolin showed that levels of EGR-1 mRNA were low at 0 h, highly increased at 6 h post-forskolin (P < 0.05), and declined to steady state thereafter. Immunoblotting confirmed forskolin-induced EGR-1 protein in cultures. Interestingly, overexpression of EGR-1 increased the levels of mRNA for prostaglandin (PG) G/H synthase-2 (PGHS-2), PG E synthase (PGES), PG E2 receptor (EP2), LH receptor (LH-R), but not for cytochrome P450-side chain cleavage (P450scc), and cytochrome P450 aromatase (P450arom) in granulosa cultures. Thus, this study reports for the first time, a gonadotropin-dependent induction of

  9. Reversing Platinum Resistance in High-Grade Serous Ovarian Carcinoma: Targeting BRCA and the Homologous Recombination System.

    PubMed

    Wiedemeyer, W Ruprecht; Beach, Jessica A; Karlan, Beth Y

    2014-01-01

    Resistance to platinum chemotherapy is one of the main factors driving ovarian cancer mortality, and overcoming platinum resistance is considered one of the greatest challenges in ovarian cancer research. Genetic and functional evidence points to the homologous recombination (HR) DNA repair system, and BRCA1 and BRCA2 in particular, as main determinants of response to platinum therapy. BRCA-mutant ovarian cancers are especially sensitive to platinum, associated with better survival, and amenable to poly ADP ribose polymerase inhibitor treatment. Here, we discuss a therapeutic concept that seeks to disrupt HR capacity via targeting of BRCA1 and BRCA2 functionality in order to reverse platinum resistance in BRCA-proficient high-grade serous ovarian cancers (HGSOC). We review the molecular signaling pathways that converge on BRCA1 and BRCA2, their activation status in ovarian cancer, and therapeutic options to modulate BRCA function. Several recent publications demonstrate efficient chemosensitization of BRCA-proficient cancers by combining targeted therapy with standard platinum-based agents. Due to its inherent genomic heterogeneity, molecularly defined subgroups of HGSOC may require different approaches. We seek to provide an overview of available agents and their potential use to reverse platinum resistance by inhibiting the HR system, either directly or indirectly, by targeting oncogenic activators of HR.

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

    PubMed Central

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

    2017-01-01

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

  11. Ovarian Cancer FAQ

    MedlinePlus

    ... cancer—Stromal cell cancer occurs in the connective tissue, which provides the internal structure of the ovary. It also has a high cure rate. What are the risk factors for epithelial ovarian cancer? Certain risk factors are associated with ...

  12. Ovarian Cancer Stage II

    MedlinePlus

    ... Download Title: Ovarian Cancer Stage II Description: Three-panel drawing of stage IIA, IIB, and stage II primary peritoneal cancer; the first panel (stage IIA) shows cancer inside both ovaries that ...

  13. Primary Ovarian Insufficiency (POI)

    MedlinePlus

    ... Overview Condition Information What are common symptoms? How many people are affected/at risk? ... Ovarian Insufficiency (POI): Condition Information Skip sharing on social media links Share this: Page Content What is POI? ...

  14. Dietary factors and epithelial ovarian cancer.

    PubMed Central

    Shu, X. O.; Gao, Y. T.; Yuan, J. M.; Ziegler, R. G.; Brinton, L. A.

    1989-01-01

    Dietary data from a population-based case-control study of 172 epithelial ovarian cancer cases and 172 controls were analysed. A significant (P less than 0.01) dose-response relationship was found between intake of fat from animal sources and risk of ovarian cancer, but plant fat was not associated. Although the effect of animal fat was confounded by education, an adjusted odds ratio of 1.8 persisted for those in the upper quartile compared to the lower quartile of consumption (P for trend = 0.03). After adjustment for animal fat intake, calorific and protein intake had minimal effects on risk. Total vegetables were found to be somewhat protective, but the mechanism of action was unclear. Weight, height and relative weight (weight/height2) were not related to risk of ovarian cancer. PMID:2757927

  15. Meeting Report: Structural Determination of Environmentally Responsive Proteins

    PubMed Central

    Reinlib, Leslie

    2005-01-01

    The three-dimensional structure of gene products continues to be a missing lynchpin between linear genome sequences and our understanding of the normal and abnormal function of proteins and pathways. Enhanced activity in this area is likely to lead to better understanding of how discrete changes in molecular patterns and conformation underlie functional changes in protein complexes and, with it, sensitivity of an individual to an exposure. The National Institute of Environmental Health Sciences convened a workshop of experts in structural determination and environmental health to solicit advice for future research in structural resolution relative to environmentally responsive proteins and pathways. The highest priorities recommended by the workshop were to support studies of structure, analysis, control, and design of conformational and functional states at molecular resolution for environmentally responsive molecules and complexes; promote understanding of dynamics, kinetics, and ligand responses; investigate the mechanisms and steps in posttranslational modifications, protein partnering, impact of genetic polymorphisms on structure/function, and ligand interactions; and encourage integrated experimental and computational approaches. The workshop participants also saw value in improving the throughput and purity of protein samples and macromolecular assemblies; developing optimal processes for design, production, and assembly of macromolecular complexes; encouraging studies on protein–protein and macromolecular interactions; and examining assemblies of individual proteins and their functions in pathways of interest for environmental health. PMID:16263521

  16. S1P differentially regulates migration of human ovarian cancer and human ovarian surface epithelial cells

    PubMed Central

    Wang, Dongmei; Zhao, Zhenwen; Caperell-Grant, Andrea; Yang, Gong; Mok, Samuel C.; Liu, Jinsong; Bigsby, Robert M.; Xu, Yan

    2009-01-01

    Epithelial ovarian cancer (EOC) arises from the epithelial layer covering the surface of ovaries and intra-peritoneal metastasis is commonly observed at diagnosis. Sphingosine-1-phosphate (S1P), a bioactive lipid signaling molecule, is potentially involved in EOC tumorigenesis. We have found that S1P is elevated in human EOC ascites. We show that physiologically relevant concentrations of S1P stimulate migration and invasion of EOC cells, but inhibit migration of human ovarian surface epithelial (HOSE) cells. In addition, S1P inhibits lysophosphatidic acid (LPA)-induced cell migration in HOSE, but not in EOC cells. We have provided the first line of evidence that the expression levels of S1P receptor subtypes are not the only determinants for how cells respond to S1P. Even though S1P1 is expressed and functional in HOSE cells, the inhibitory effect mediated by S1P2 is dominant in those cells. The cellular pre-existing stress fibers are also important determinants for the migratory response to S1P. Differential S1P-induced morphology changes are noted in EOC and HOSE cells. Pre-existing stress fibers in HOSE cells are further enhanced by S1P treatment, resulting in the negative migratory response to S1P. By contrast, EOC cells lost stress fibers and S1P treatment induces filopodium-like structures at cell edges, which correlates with increased cell motility. In addition, inhibition of the protein kinase C pathway is likely to be involved in the inhibitory effect of S1P on LPA-induced cell migration in HOSE cells. These findings are important for the development of new therapeutics targeting S1P and LPA in EOC. PMID:18645009

  17. [Actinomycotic tubo-ovarian abscess. Contribution of pelvic angioscanner].

    PubMed

    Bazot, M; Davenne, C; Benzakine, Y; Boudghène, F; Bigot, J M

    1997-07-01

    Pelvic actinomycosis is uncommon and usually responsible for tubo-ovarian abscesses which are similar in aspect with nonactinomycotic abscesses. They are usually a complication of an intra-uterine device (IUD) that can be absent as in this case. The differential diagnosis is ovarian cancer. The role of the dynamic CT scan for differential diagnosis in this case is presented. Preoperative diagnosis in this affection is important because of the excellent response to Penicillin.

  18. Experimental determination of storage ring optics using orbit response measurements

    NASA Astrophysics Data System (ADS)

    Safranek, J.

    1997-02-01

    The measured response matrix giving the change in orbit at beam position monitors (BPMs) with changes in steering magnet excitation can be used to accurately calibrate the linear optics in an electron storage ring [1-8]. A computer code called LOCO (Linear Optics from Closed Orbits) was developed to analyze the NSLS X-Ray Ring measured response matrix to determine: the gradients in all 56 quadrupole magnets; the calibration of the steering magnets and BPMs; the roll of the quadrupoles, steering magnets, and BPMs about the electron beam direction; the longitudinal magnetic centers of the orbit steering magnets; the horizontal dispersion at the orbit steering magnets; and the transverse mis-alignment of the electron orbit in each of the sextupoles. Random orbit measurement error from the BPMs propagated to give only 0.04% rms error in the determination of individual quadrupole gradients and 0.4 mrad rms error in the determination of individual quadrupole rolls. Small variations of a few parts in a thousand in the quadrupole gradients within an individual family were resolved. The optics derived by LOCO gave accurate predictions of the horizontal dispersion, the beta functions, and the horizontal and vertical emittances, and it gave good qualitative agreement with the measured vertical dispersion. The improved understanding of the X-Ray Ring has enabled us to increase the synchrotron radiation brightness. The LOCO code can also be used to find the quadrupole family gradients that best correct for gradient errors in quadrupoles, in sextupoles, and from synchrotron radiation insertion devices. In this way the design periodicity of a storage ring's optics can be restored. An example of periodicity restoration will be presented for the NSLS VUV Ring. LOCO has also produced useful results when applied to the ALS storage ring [8].

  19. High dose intensity combination chemotherapy for advanced epithelial ovarian carcinoma: results of a pilot study.

    PubMed Central

    Sweetenham, J. W.; McKendrick, J. J.; Jones, D. H.; Whitehouse, J. M.; Williams, C. J.

    1990-01-01

    Retrospective studies have recently demonstrated a significant correlation between dose intensity of chemotherapy and response rates and survival in various diseases including epithelial ovarian carcinoma. As part of a proposed randomised trial to assess the effect of dose intensity on outcome in ovarian carcinoma, a pilot study has been undertaken to determine the toxicity and efficacy of the high intensity therapy. Nineteen patients with advanced ovarian carcinoma received initial treatment with cisplatin 120 mg m-2 i.v. day 1, and cyclophosphamide 1,000 mg-2 i.v. day 1, given at 21-day intervals for six cycles. The average relative dose intensity of this therapy is 1.14 when compared with the CHAP regimen. Severe toxicity was experienced by most patients. The median received average relative dose intensity was 0.90, with only one patient receiving treatment to the proposed intensity. Randomised studies of the effect of dose intensity in ovarian carcinoma are essential, but an initial step must be to assess whether the proposed high dose treatment can be delivered. PMID:2155645

  20. [Ovarian pregnancy: about 3 cases and review of the literature].

    PubMed

    Ranaivoson, Haingo Voahangy Rabetafika; Ranaivomanana, Volahasina Françine; Nomenjanahary, Lalaina; Andriamampionona, Tsitohery Francine; Randrianjafisamindrakotroka, Nantenaina Soa

    2016-01-01

    Ovarian pregnancy is a rare event among women with ectopic pregnancy in whom the ovary is the site of implantation. Its diagnosis requires a well codified approach. The peculiarities of the determining factors, of the histopathological and evolutionary features typical of ovarian pregnancies led us to focus on this form of ectopic pregnancy. We report 3 cases of ovarian pregnancy diagnosed in our Department. The three women were between 30 and 42 years, at 13 to 37 weeks of amenorrhea. All women had abdominal pain of varying intensity associated with shock. Anatomopathological examination of the right annex, normal site of implantation of ovarian pregnancies, confirmed the diagnosis. All women had juxtaposition ovarian cortical pregnancy. Ovarian pregnancy is a rare event among women with ectopic pregnancy, having specific peculiarities. Its diagnosis is difficult and is based on preoperative findings. The identification of the ovarian implantation on histopathological examination is ideal for confirming the diagnosis. Currently, it is assumed that ovarian pregnancy is the form of ectopic pregnancy which can develop to term or even result in a live birth.

  1. Histogenesis of ovarian malignant mixed mesodermal tumours.

    PubMed Central

    Clarke, T J

    1990-01-01

    The histogenesis of ovarian malignant mixed mesodermal tumours, which includes the concept of metaplastic carcinoma, is controversial. Four such tumours were examined for evidence of metaplastic transition from carcinoma to sarcoma using morphology and reticulin stains. Consecutive sections were stained immunohistochemically using cytokeratin and vimentin to determine whether cells at the interface between carcinoma and sarcoma expressed both cytokeratin and vimentin. There was no evidence of morphological, architectural, or immunohistochemical transitions from carcinoma to sarcoma in the four tumours studied. This suggests that ovarian malignant mixed mesodermal tumours are not metaplastic carcinomas but are composed of histogenetically different elements. Images PMID:2160478

  2. Algorithms for Determining Physical Responses of Structures Under Load

    NASA Technical Reports Server (NTRS)

    Richards, W. Lance; Ko, William L.

    2012-01-01

    Ultra-efficient real-time structural monitoring algorithms have been developed to provide extensive information about the physical response of structures under load. These algorithms are driven by actual strain data to measure accurately local strains at multiple locations on the surface of a structure. Through a single point load calibration test, these structural strains are then used to calculate key physical properties of the structure at each measurement location. Such properties include the structure s flexural rigidity (the product of the structure's modulus of elasticity, and its moment of inertia) and the section modulus (the moment of inertia divided by the structure s half-depth). The resulting structural properties at each location can be used to determine the structure s bending moment, shear, and structural loads in real time while the structure is in service. The amount of structural information can be maximized through the use of highly multiplexed fiber Bragg grating technology using optical time domain reflectometry and optical frequency domain reflectometry, which can provide a local strain measurement every 10 mm on a single hair-sized optical fiber. Since local strain is used as input to the algorithms, this system serves multiple purposes of measuring strains and displacements, as well as determining structural bending moment, shear, and loads for assessing real-time structural health. The first step is to install a series of strain sensors on the structure s surface in such a way as to measure bending strains at desired locations. The next step is to perform a simple ground test calibration. For a beam of length l (see example), discretized into n sections and subjected to a tip load of P that places the beam in bending, the flexural rigidity of the beam can be experimentally determined at each measurement location x. The bending moment at each station can then be determined for any general set of loads applied during operation.

  3. Targeting epithelial-mesenchymal transition and cancer stem cells for chemoresistant ovarian cancer

    PubMed Central

    Deng, Junli; Wang, Li; Chen, Hongmin; Hao, Jingli; Ni, Jie; Chang, Lei; Duan, Wei; Graham, Peter; Li, Yong

    2016-01-01

    Chemoresistance is the main challenge for the recurrent ovarian cancer therapy and responsible for treatment failure and unfavorable clinical outcome. Understanding mechanisms of chemoresistance in ovarian cancer would help to predict disease progression, develop new therapies and personalize systemic therapy. In the last decade, accumulating evidence demonstrates that epithelial-mesenchymal transition and cancer stem cells play important roles in ovarian cancer chemoresistance and metastasis. Treatment of epithelial-mesenchymal transition and cancer stem cells holds promise for improving current ovarian cancer therapies and prolonging the survival of recurrent ovarian cancer patients in the future. In this review, we focus on the role of epithelial-mesenchymal transition and cancer stem cells in ovarian cancer chemoresistance and explore the therapeutic implications for developing epithelial-mesenchymal transition and cancer stem cells associated therapies for future ovarian cancer treatment. PMID:27304054

  4. Can Ovarian Cancer Be Prevented?

    MedlinePlus

    ... a family history of ovarian cancer or BRCA mutation If your family history suggests that you (or ... are likely to have one of the gene mutations associated with an increased ovarian cancer risk. The ...

  5. Determinants of paramedic response readiness for CBRNE threats.

    PubMed

    Stevens, Garry; Jones, Alison; Smith, George; Nelson, Jenny; Agho, Kingsley; Taylor, Melanie; Raphael, Beverley

    2010-06-01

    Paramedics play a pivotal role in the response to major emergencies. Recent evidence indicates that their confidence and willingness to respond to chemical, biological, radiological, nuclear, and explosives-related (CBRNE) incidents differs from that relating to their "routine" emergency work. To further investigate the factors underpinning their readiness to respond to CBRNE incidents, paramedics in New South Wales (NSW), Australia, were asked to complete a validated online survey instrument. Univariate and multivariate analyses were performed to examine associated factors determining readiness. The sample of 663 respondents was weighted to reflect the NSW paramedic population as a whole. The univariate analysis indicated that gender, length of service, deployment concern, perceived personal resilience, CBRNE training, and incident experience were significantly associated with perceived CBRNE response readiness. In the initial multivariate analysis, significantly higher response readiness was associated with male gender, university education, and greater length of service (10-15 years). In the final multivariate model, the combined effect of training/incident experience negated the significant effects observed in the initial model and, importantly, showed that those with recent training reported higher readiness, irrespective of incident experience. Those with lower concern regarding CBRNE deployment and those with higher personal resilience were significantly more likely to report higher readiness (Adjusted Relative Risk [ARR] = 0.91, 95% CI: 0.84-0.99; ARR = 1.40, 95% CI: 1.11-1.72, respectively). These findings will assist emergency medical planners in recognizing occupational and dispositional factors associated with enhanced CBRNE readiness and highlight the important role of training in redressing potential readiness differences associated with these factors.

  6. Genetic Modifiers of Ovarian Cancer

    DTIC Science & Technology

    2013-06-01

    cancer suggesting the presence of genetic modifiers of ovarian cancer in this population. A genome wide association study ( GWAS ) for ovarian cancer...cancer and 1,000 age-matched unaffected BRCA1 carriers. As outlined in detail in our previous annual report, we recently conducted a GWAS of BRCA1...between ovarian cancer risk and SNPs implicated in Aim 1 by genotyping 1,500 BRCA1 ovarian cancer cases and 1,500 unaffected BRCA1 carriers. GWAS

  7. Primary ovarian insufficiency in classic galactosemia: role of FSH dysfunction and timing of the lesion.

    PubMed

    Gubbels, Cynthia S; Land, Jolande A; Evers, Johannes L H; Bierau, Jörgen; Menheere, Paul P C A; Robben, Simon G F; Rubio-Gozalbo, M Estela

    2013-01-01

    FSH inactivity due to secondary hypoglycosylation has been suggested as a potential mechanism for primary ovarian insufficiency in classic galactosemia. To investigate the role of FSH and to gain insight in the timing of the damage, ovarian stimulation tests were performed and data on ovarian imaging collected. Fifteen patients with primary ovarian insufficiency underwent ovarian stimulation with gonadotropins. Only one patient showed a normal increase in estradiol level, all the others had a low or no estradiol response. Anti-Müllerian hormone measurement in all girls and women showed levels below the detection limit of 0.10 μg/l. Ovarian volumes were evaluated by MRI in 14 patients and compared to age matched controls, prepubertal controls and postmenopausal controls. The ovarian volumes of the galactosemic girls were smaller than those of the age matched controls (p = 0.001) and the prepubertal ovaries (p = 0.008), and did not differ significantly from postmenopausal ovarian volumes (p = 0.161). In conclusion we found no evidence that FSH inactivity plays a role in primary ovarian insufficiency in classic galactosemia. Moreover, ovarian imaging results point to an early onset of ovarian failure in this disease.

  8. Ovarian ectopic pregnancy in adolescence

    PubMed Central

    Andrade, Ana Gonçalves; Rocha, Sara; Marques, Catarina O; Simões, Mafalda; Martins, Isabel; Biscaia, Isabel; F Barros, Carlos

    2015-01-01

    Key Clinical Message Ovarian pregnancy is one of the rarest types of extrauterine pregnancy. Its preoperative diagnosis remains a challenge since it presents quite similarly to tubal pregnancy and complicated ovarian cysts. Although in most cases, histology is necessary to confirm the diagnosis, we present an ovarian pregnancy in a teenager, correctly diagnosed during ultrasound examination. PMID:26576271

  9. Akt isoform specific effects in ovarian cancer progression

    PubMed Central

    Linnerth-Petrik, Nicolle M.; Santry, Lisa A.; Moorehead, Roger; Jücker, Manfred

    2016-01-01

    Ovarian cancer remains a significant therapeutic problem and novel, effective therapies are needed. Akt is a serine-threonine kinase that is overexpressed in numerous cancers, including ovarian. Mammalian cells express three Akt isoforms which are encoded by distinct genes. Although there are several Akt inhibitors in clinical trials, most indiscriminately target all isoforms. Current in vitro data and animal knockout experiments suggest that the Akt isoforms may have divergent roles. In this paper, we determined the isoform-specific functions of Akt in ovarian cancer cell proliferation in vitro and in ovarian cancer progression in vivo. For in vitro experiments, murine and human ovarian cancer cells were treated with Akt inhibitors and cell viability was assessed. We used two different in vivo approaches to identify the roles of Akt isoforms in ovarian cancer progression and their influence on the primary tumor and tumor microenvironment. In one experiment, wild-type C57Bl6 mice were orthotopically injected with ID8 cells with stable knockdown of Akt isoforms. In a separate experiment, mice null for Akt 1-3 were orthotopically injected with WT ID8 cells (Figure 1). Our data show that inhibition of Akt1 significantly reduced ovarian cancer cell proliferation and inhibited tumor progression in vivo. Conversely, disruption of Akt2 increased tumor growth. Inhibition of Akt3 had an intermediate phenotype, but also increased growth of ovarian cancer cells. These data suggest that there is minimal redundancy between the Akt isoforms in ovarian cancer progression. These findings have important implications in the design of Akt inhibitors for the effective treatment of ovarian cancer. PMID:27533079

  10. Xenobiotic Effects on Ovarian Preantral Follicles1

    PubMed Central

    Mark-Kappeler, Connie J.; Hoyer, Patricia B.; Devine, Patrick J.

    2011-01-01

    Women are born with a finite population of ovarian follicles, which are slowly depleted during their reproductive years until reproductive failure (menopause) occurs. The rate of loss of primordial follicles is determined by genetic and environmental influences, but certain toxic exposures can accelerate this process. Ionizing radiation reduces preantral follicle numbers in rodents and humans in a dose-dependent manner. Cigarette smoking is linked to menopause occurring 1–4 yr earlier than with nonsmokers, and components of smoke, polycyclic aromatic hydrocarbons, can cause follicle depletion in rodents or in ovaries in vitro. Chemotherapeutic agents, such as alkylating drugs and cisplatin, also cause loss of preantral ovarian follicles. Effects depend on dose, type, and reactivity of the drug, and the age of the individual. Evidence suggests DNA damage may underlie follicle loss induced by one common alkylating drug, cyclophosphamide. Occupational exposures have also been linked to ovarian damage. In an industrial setting, 2-bromopropane caused infertility in men and women, and it can induce ovarian follicle depletion in rats. Solvents, such as butadiene, 4-vinylcyclohexene, and their diepoxides, can also cause specific preantral follicle depletion. The mechanism(s) underlying effects of the latter compound may involve alterations in apoptosis, survival factors such as KIT/Kit Ligand, and/or the cellular signaling that maintains primordial follicle dormancy. Estrogenic endocrine disruptors may alter follicle formation/development and impair fertility or normal development of offspring. Thus, specific exposures are known or suspected of detrimentally impacting preantral ovarian follicles, leading to early ovarian failure. PMID:21697514

  11. Prevention of Ovarian High-Grade Serous Carcinoma by Elucidating Its Early Change

    DTIC Science & Technology

    2013-10-01

    for ovarian cancer. In addition, Project 5 will determine if these biomarkers and associated precursor lesions are modifiable by oral contraceptives ...3. Determine whether oral contraceptives (OCPs) and NSAIDs reduce the morphologic and molecular changes that are associated with early “ovarian... contraceptives (OCPs) or anti- inflammatory agents, as OCPs in particular are known to prevent ovarian cancer and impact survival. Research site: Johns

  12. Ovarian innervation develops before initiation of folliculogenesis in the rat.

    PubMed

    Malamed, S; Gibney, J A; Ojeda, S R

    1992-10-01

    Sympathetic neurotransmitters have been shown to be present in the ovary of the rat during early postnatal development and to affect steroidogenesis before the ovary becomes responsive to gonadotropins, and before the first primordial follicles are formed. This study was undertaken to determine if development of the ovarian innervation is an event that antedates the initiation of folliculogenesis in the rat, Rattus norvegicus. Serial sections of postnatal ovaries revealed a negligible frequency of follicles 24 h after birth (about 1 primordial follicle per ovary). Twelve hours later there were about 500 follicles per ovary, a number that more than doubled to about 1300 during the subsequent 12 h, indicating that an explosive period of follicular differentiation occurs between the end of postnatal days 1 and 2. Electron microscopy demonstrated that before birth the ovaries are already innervated by fibers containing clear and dense-core vesicles. Immunohistochemistry performed on either fetal (day 19) or newborn (less than 15h after birth) ovaries showed the presence of catecholaminergic nerves, identified by their content of immunoreactive tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis. While some of these fibers innervate blood vessels, others are associated with primordial ovarian cells, thereby suggesting their participation in non-vascular functions. Since prefollicular ovaries are insensitive to gonadotropins, the results suggest that the developing ovary becomes subjected to direct neurogenic influences before it acquires responsiveness to gonadotropins.

  13. Ovarian tumor characterization using 3D ultrasound.

    PubMed

    Acharya, U Rajendra; Sree, S Vinitha; Krishnan, M Muthu Rama; Saba, Luca; Molinari, Filippo; Guerriero, Stefano; Suri, Jasjit S

    2012-12-01

    Among gynecological malignancies, ovarian cancer is the most frequent cause of death. Preoperative determination of whether a tumor is benign or malignant has often been found to be difficult. Because of such inconclusive findings from ultrasound images and other tests, many patients with benign conditions have been offered unnecessary surgeries thereby increasing patient anxiety and healthcare cost. The key objective of our work is to develop an adjunct Computer Aided Diagnostic (CAD) technique that uses ultrasound images of the ovary and image mining algorithms to accurately classify benign and malignant ovarian tumor images. In this algorithm, we extract texture features based on Local Binary Patterns (LBP) and Laws Texture Energy (LTE) and use them to build and train a Support Vector Machine (SVM) classifier. Our technique was validated using 1000 benign and 1000 malignant images, and we obtained a high accuracy of 99.9% using a SVM classifier with a Radial Basis Function (RBF) kernel. The high accuracy can be attributed to the determination of the novel combination of the 16 texture based features that quantify the subtle changes in the images belonging to both classes. The proposed algorithm has the following characteristics: cost-effectiveness, complete automation, easy deployment, and good end-user comprehensibility. We have also developed a novel integrated index, Ovarian Cancer Index (OCI), which is a combination of the texture features, to present the physicians with a more transparent adjunct technique for ovarian tumor classification.

  14. Determining blood and plasma volumes using bioelectrical response spectroscopy

    NASA Technical Reports Server (NTRS)

    Siconolfi, S. F.; Nusynowitz, M. L.; Suire, S. S.; Moore, A. D. Jr; Leig, J.

    1996-01-01

    We hypothesized that an electric field (inductance) produced by charged blood components passing through the many branches of arteries and veins could assess total blood volume (TBV) or plasma volume (PV). Individual (N = 29) electrical circuits (inductors, two resistors, and a capacitor) were determined from bioelectrical response spectroscopy (BERS) using a Hewlett Packard 4284A Precision LCR Meter. Inductance, capacitance, and resistance from the circuits of 19 subjects modeled TBV (sum of PV and computed red cell volume) and PV (based on 125I-albumin). Each model (N = 10, cross validation group) had good validity based on 1) mean differences (-2.3 to 1.5%) between the methods that were not significant and less than the propagated errors (+/- 5.2% for TBV and PV), 2) high correlations (r > 0.92) with low SEE (< 7.7%) between dilution and BERS assessments, and 3) Bland-Altman pairwise comparisons that indicated "clinical equivalency" between the methods. Given the limitation of this study (10 validity subjects), we concluded that BERS models accurately assessed TBV and PV. Further evaluations of the models' validities are needed before they are used in clinical or research settings.

  15. Is assessment of anti-Müllerian hormone and/or antral follicle count useful in the prediction of ovarian response in expected normal responders treated with a fixed dose of recombinant FSH and GnRH antagonists? A prospective observational study.

    PubMed

    Ganidou, Maria A; Kolibianakis, Efstratios M; Venetis, Christos A; Gerou, Spiros; Makedos, Georgios A; Klearchou, Nikolaos; Tarlatzis, Basil C

    2014-11-01

    The purpose of this prospective observational study was to evaluate whether the assessment of AMH and AFC is useful in the prediction of ovarian response in expected normal responders treated with a fixed dose of recombinant FSH (rec-FSH) and GnRH antagonists. A base model including age and basal FSH as independent predictors of COCs could explain 15% of the variance observed in the number of COCs retrieved (p = 0.002). The addition of AFC did not increase significantly the predictive ability of the above model, whereas the addition of AMH increased the performance of the base model by 13% (p < 0.001). Logistic regression analysis showed that only when AMH was added to the base model, including age and FSH, its predictive capacity for high ovarian response was statistically significant (F-test: p = 0.001; c-statistic: 0.80, 95% CI: 0.70-0.88), but this was not the case for poor ovarian response. In conclusion, the addition of AMH, but not of AFC, to a model including female age and basal FSH, is useful in the prediction of ovarian response in expected normal responders treated with a fixed dose of recombinant FSH and GnRH antagonists.

  16. Epithelial membrane protein 1 expression in ovarian serous tumors.

    PubMed

    Demirag, Guzin Gonullu; Kefeli, Mehmet; Kemal, Yasemin; Yucel, Idris

    2016-03-01

    The present study aimed to analyze the clinical significance of epithelial membrane protein 1 (EMP1) expression in ovarian serous tumors. A total of 84 cases of ovarian serous tumor (50 patients with malignant ovarian serous tumors and 34 patients with borderline and benign serous tumors) were retrospectively analyzed. Differences in the expression levels of EMP1 between the malignant and non-malignant tumor groups were evaluated by immunohistochemical staining. In addition, the association between EMP1 expression and prognostic factors in malignant ovarian serous tumors was investigated. The expression levels of EMP1 were significantly reduced in all the 50 malignant ovarian serous tumors, compared with the 34 non-malignant ovarian serous tumors (P<0.000). Reduced expression of EMP1 was correlated with high grade (P=0.009) and stage (P<0.000) of malignant tumors. EMP1 expression was not observed to be correlated with any other investigated parameters, including surgery, type of operation and chemotherapy response (P>0.005). These results indicated that EMP1 may have a significant role as a negative regulator in ovarian serous tumors, and reduced EMP1 expression in serous tumors may be associated with increased disease severity.

  17. Regulation of HSulf-1 expression by variant hepatic nuclear factor 1 (vHNF1) in ovarian cancer

    PubMed Central

    Liu, Peng; Khurana, Ashwani; Rattan, Ramandeep; He, Xiaoping; Kalloger, Steve; Dowdy, Sean; Gilks, Blake; Shridhar, Viji

    2009-01-01

    We recently identified HSulf-1 as a downregulated gene in ovarian carcinomas. Our previous analysis indicated that HSulf-1 inactivation in ovarian cancers is partly mediated by loss of heterozygosity (LOH) and epigenetic silencing. Here we demonstrate that variant hepatic nuclear factor 1 (vHNF1), encoded by transcription factor 2 gene (TCF2, HNF-1β) negatively regulates HSulf-1 expression in ovarian cancer. Immunoblot assay revealed that vHNF1 is highly expressed in HSulf-1 deficient OV207, SKOV3 and TOV-21G cell lines but not in HSulf-1 expressing OSE, OV167 and OV202 cells. By shRNA-mediated downregulation of vHNF1 in TOV21-G cells and transient enhanced vHNF1 expression in OV202 cells, we showed that vHNF1 suppresses HSulf-1 expression in ovarian cancer cell lines. Reporter assay and chromatin immunoprecipitation (ChIP) experiments showed that vHNF1 is specifically recruited to HSulf-1 promoter at two different vHNF1 responsive elements in OV207 and TOV-21G cells. Additionally, downregulation of vHNF1 expression in OV207 and TOV-21G cells increased cisplatin- or paclitaxel-mediated cytotoxicity as determined by both MTT and clonogenic assays and this effect was reversed by downregulation of HSulf-1. Moreover, nude mice bearing TOV-21G cell xenografts with stably downregulated vHNF1 were more sensitive to cisplatin-or paclitaxel-induced cytotoxicity compared to xenografts of TOV-21G clonal lines with nontargeted control shRNA. Finally, immunohistochemical analysis of 501 ovarian tumors including 140 clear cell tumors on tissue microarrays showed that vHNF1 inversely correlates to HSulf-1 expression. Collectively, these results indicate that vHNF1 acts as a repressor of HSulf-1 expression and might be a molecular target for ovarian cancer therapy. PMID:19487294

  18. ST6Gal-I expression in ovarian cancer cells promotes an invasive phenotype by altering integrin glycosylation and function

    PubMed Central

    Christie, Daniel R; Shaikh, Faheem M; Lucas, John A; Lucas, John A; Bellis, Susan L

    2008-01-01

    Background Ovarian adenocarcinoma is not generally discovered in patients until there has been widespread intraperitoneal dissemination, which is why ovarian cancer is the deadliest gynecologic malignancy. Though incompletely understood, the mechanism of peritoneal metastasis relies on primary tumor cells being able to detach themselves from the tumor, escape normal apoptotic pathways while free floating, and adhere to, and eventually invade through, the peritoneal surface. Our laboratory has previously shown that the Golgi glycosyltransferase, ST6Gal-I, mediates the hypersialylation of β1 integrins in colon adenocarcinoma, which leads to a more metastatic tumor cell phenotype. Interestingly, ST6Gal-I mRNA is known to be upregulated in metastatic ovarian cancer, therefore the goal of the present study was to determine whether ST6Gal-I confers a similarly aggressive phenotype to ovarian tumor cells. Methods Three ovarian carcinoma cell lines were screened for ST6Gal-I expression, and two of these, PA-1 and SKOV3, were found to produce ST6Gal-I protein. The third cell line, OV4, lacked endogenous ST6Gal-I. In order to understand the effects of ST6Gal-I on cell behavior, OV4 cells were stably-transduced with ST6Gal-I using a lentiviral vector, and integrin-mediated responses were compared in parental and ST6Gal-I-expressing cells. Results Forced expression of ST6Gal-I in OV4 cells, resulting in sialylation of β1 integrins, induced greater cell adhesion to, and migration toward, collagen I. Similarly, ST6Gal-I expressing cells were more invasive through Matrigel. Conclusion ST6Gal-I mediated sialylation of β1 integrins in ovarian cancer cells may contribute to peritoneal metastasis by altering tumor cell adhesion and migration through extracellular matrix. PMID:19014651

  19. Ovarian hormones and drug abuse.

    PubMed

    Moran-Santa Maria, Megan M; Flanagan, Julianne; Brady, Kathleen

    2014-11-01

    There are significant gender differences in course, symptomology, and treatment of substance use disorders. In general data from clinical and preclinical studies of substance use disorders suggest that women are more vulnerable than men to the deleterious consequences of drug use at every phase of the addiction process. In addition data from epidemiologic studies suggest that the gender gap in the prevalence of substance use is narrowing particularly among adolescence. Therefore, understanding the role of estrogen and progesterone in mediating responses to drugs of abuse is of critical importance to women's health. In this review we will discuss findings from clinical and preclinical studies of (1) reproductive cycle phase; (2) endogenous ovarian hormones; and (3) hormone replacement on responses to stimulants, nicotine, alcohol, opioids, and marijuana. In addition, we discuss data from recent studies that have advanced our understanding of the neurobiologic mechanisms that interact with estrogen and progesterone to mediate drug-seeking behavior.

  20. In vitro sensitivity of human ovarian tumours to chemotherapeutic agents.

    PubMed Central

    Wilson, A. P.; Neal, F. E.

    1981-01-01

    The in vitro chemosensitivity of primary monolayer cultures of human ovarian tumours to a wide range of chemotherapeutic agents has been determined using 3H-leucine incorporation as an index of cytotoxicity. Of 67 specimens received, 35 have been successfully cultured and tested for chemosensitivity. Drugs tested included alkylating agents, antibiotics, antimitotics, antimetabolites and progestogens. The overall incidence of efficacy of the drugs corresponded with the incidence which might be expected from data on the clinical response rates produced by the various drugs. Cultures from the tumour cells of treated patients generally showed greater resistance than tumours of untreated patients. Correlation between in vitro results and in vivo response was positive in all 8 patients receiving first-line chemotherapy and in 57% (4/7) patients receiving second-line chemotherapy. PMID:6791675

  1. Is immune system-related hypertension associated with ovarian hormone deficiency?

    PubMed Central

    Sandberg, Kathryn; Ji, Hong; Einstein, Gillian; Au, April; Hay, Meredith

    2017-01-01

    The immune system is known to contribute to the development of high blood pressure in males. However, the role of the immune system in the development of high blood pressure in females and the role of ovarian hormones has only recently begun to be studied. In animal studies, both the sex of the host and the T cell are critical biological determinants of susceptibility and resistance to hypertension induced by angiotensin II. In women, natural menopause is known to result in significant changes in the expression of genes regulating the immune system. Likewise, in animal models, ovariectomy results in hypertension and an upregulation in T-cell tumour necrosis factor-α-related genes. Oestrogen replacement results in decreases in inflammatory genes in the brain regions involved in blood pressure regulation. Together, these studies suggest that the response of the adaptive immune system to ovarian hormone deficiency is a significant contributor to hypertension in women. PMID:26419911

  2. CA 125 in monitoring chemotherapy of the patients with ovarian cancer.

    PubMed

    Markowska, J; Kojczynski, Z; Szewierski, Z; Manys, G

    1990-01-01

    Changes in CA 125 antigen concentration and serum half-life were determined in 63 women with ovarian carcinoma during chemotherapy following various types of surgery. Concentration of CA 125 in serum correlated with the degree of clinical advancement of the tumor, 20.00 and 688.84 U per ml at stages I, II, and IV, respectively, and with remaining tumor mass, despite chemotherapy, serum CA 125 level rose after exploratory surgery. Estimation of CA 125 levels proved less useful in the mucinous type of ovarian carcinoma. The treatment scheme including Cisplatinum reduced CA 125 levels most effectively correlated with good clinical response to the therapy. Testing the half-life time appeared to provide a good prognostic index, 6.25 +/- 2.08 days after radical surgery and 44.87 +/- 26.5 days after probatory laparotomy.

  3. Denileukin Diftitox Used in Treating Patients With Advanced Refractory Ovarian Cancer, Primary Peritoneal Carcinoma, or Epithelial Fallopian Tube Cancer

    ClinicalTrials.gov

    2016-05-02

    Fallopian Tube Cancer; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Epithelial Carcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Undifferentiated Adenocarcinoma; Peritoneal Cavity Cancer; Recurrent Ovarian Epithelial Cancer; Stage III Ovarian Epithelial Cancer; Stage IV Ovarian Epithelial Cancer

  4. Cognitive and Ocular Factors Jointly Determine Pupil Responses under Equiluminance

    PubMed Central

    Brascamp, Jan; Nuiten, Stijn; Hoppenbrouwers, Sylco; Theeuwes, Jan

    2016-01-01

    Changes in pupil diameter can reflect high-level cognitive signals that depend on central neuromodulatory mechanisms. However, brain mechanisms that adjust pupil size are also exquisitely sensitive to changes in luminance and other events that would be considered a nuisance in cognitive experiments recording pupil size. We implemented a simple auditory experiment involving no changes in visual stimulation. Using finite impulse-response fitting we found pupil responses triggered by different types of events. Among these are pupil responses to auditory events and associated surprise: cognitive effects. However, these cognitive responses were overshadowed by pupil responses associated with blinks and eye movements, both inevitable nuisance factors that lead to changes in effective luminance. Of note, these latter pupil responses were not recording artifacts caused by blinks and eye movements, but endogenous pupil responses that occurred in the wake of these events. Furthermore, we identified slow (tonic) changes in pupil size that differentially influenced faster (phasic) pupil responses. Fitting all pupil responses using gamma functions, we provide accurate characterisations of cognitive and non-cognitive response shapes, and quantify each response's dependence on tonic pupil size. These results allow us to create a set of recommendations for pupil size analysis in cognitive neuroscience, which we have implemented in freely available software. PMID:27191166

  5. Targeted immune therapy of ovarian cancer.

    PubMed

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

    2015-03-01

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

  6. Targeted Immune Therapy of Ovarian Cancer

    PubMed Central

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

    2014-01-01

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

  7. Palliative Surgical Approach in Advanced Nonresponsive Mucinous Ovarian Cancer: A Rare Case Report

    PubMed Central

    Agarwal, Manika; Kumar, Ritesh; Topno, Noor; Mishra, Shweta; Dhirasaria, Ashish; Singh, A Santa

    2016-01-01

    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. PMID:27162429

  8. Cell of Origin: Exploring an Alternative Contributor to Ovarian Cancer

    DTIC Science & Technology

    2014-09-01

    Our studies to date have determined that human oogonial stem cells , while far less stable than their murine counterparts, can be successfully expanded...DNA signature of the oogonial stem cell -derived tumors to that of primary human ovarian cancer. We have also successfully introduced in human...oogonial stem cells genetic alterations commonly detected in ovarian cancer. We are now generating tumors from these altered oogonial stem cells and will

  9. Role of Receptor Sialylation in the Ovarian Tumor Cell Phenotype

    DTIC Science & Technology

    2012-06-01

    blocks apoptosis induced by the mammalian lectin, galectin - 3 , which our studies show is expressed in human ovarian tumor tissues and in ascitic fluid...omental cultures. • Optimized immunoblotting protocol for galectin - 3 in ascites • Determination that sialylation of Fas and TNFR1 blocks apoptotic...REPORT DATE 2. REPORT TYPE Annual report 3 . DATES COVERED 4. TITLE AND SUBTITLE Role of receptor sialylation in the ovarian tumor cell

  10. Ovarian hyperstimulation syndrome

    MedlinePlus

    ... 3 to 6% of women who go through in vitro fertilization . Other risk factors for OHSS include: Being younger ... A.M. Editorial team. Related MedlinePlus Health Topics Assisted Reproductive Technology Ovarian Disorders Browse the Encyclopedia A.D.A. ...

  11. Gene expression profiling of human ovarian tumours

    PubMed Central

    Biade, S; Marinucci, M; Schick, J; Roberts, D; Workman, G; Sage, E H; O'Dwyer, P J; LiVolsi, V A; Johnson, S W

    2006-01-01

    There is currently a lack of reliable diagnostic and prognostic markers for ovarian cancer. We established gene expression profiles for 120 human ovarian tumours to identify determinants of histologic subtype, grade and degree of malignancy. Unsupervised cluster analysis of the most variable set of expression data resulted in three major tumour groups. One consisted predominantly of benign tumours, one contained mostly malignant tumours, and one was comprised of a mixture of borderline and malignant tumours. Using two supervised approaches, we identified a set of genes that distinguished the benign, borderline and malignant phenotypes. These algorithms were unable to establish profiles for histologic subtype or grade. To validate these findings, the expression of 21 candidate genes selected from these analyses was measured by quantitative RT–PCR using an independent set of tumour samples. Hierarchical clustering of these data resulted in two major groups, one benign and one malignant, with the borderline tumours interspersed between the two groups. These results indicate that borderline ovarian tumours may be classified as either benign or malignant, and that this classifier could be useful for predicting the clinical course of borderline tumours. Immunohistochemical analysis also demonstrated increased expression of CD24 antigen in malignant versus benign tumour tissue. The data that we have generated will contribute to a growing body of expression data that more accurately define the biologic and clinical characteristics of ovarian cancers. PMID:16969345

  12. Gene expression profiling of human ovarian tumours.

    PubMed

    Biade, S; Marinucci, M; Schick, J; Roberts, D; Workman, G; Sage, E H; O'Dwyer, P J; Livolsi, V A; Johnson, S W

    2006-10-23

    There is currently a lack of reliable diagnostic and prognostic markers for ovarian cancer. We established gene expression profiles for 120 human ovarian tumours to identify determinants of histologic subtype, grade and degree of malignancy. Unsupervised cluster analysis of the most variable set of expression data resulted in three major tumour groups. One consisted predominantly of benign tumours, one contained mostly malignant tumours, and one was comprised of a mixture of borderline and malignant tumours. Using two supervised approaches, we identified a set of genes that distinguished the benign, borderline and malignant phenotypes. These algorithms were unable to establish profiles for histologic subtype or grade. To validate these findings, the expression of 21 candidate genes selected from these analyses was measured by quantitative RT-PCR using an independent set of tumour samples. Hierarchical clustering of these data resulted in two major groups, one benign and one malignant, with the borderline tumours interspersed between the two groups. These results indicate that borderline ovarian tumours may be classified as either benign or malignant, and that this classifier could be useful for predicting the clinical course of borderline tumours. Immunohistochemical analysis also demonstrated increased expression of CD24 antigen in malignant versus benign tumour tissue. The data that we have generated will contribute to a growing body of expression data that more accurately define the biologic and clinical characteristics of ovarian cancers.

  13. Blood Cell Mitochondrial DNA Content and Premature Ovarian Aging

    PubMed Central

    Cacciatore, Chiara; Busnelli, Marta; Rossetti, Raffaella; Bonetti, Silvia; Paffoni, Alessio; Mari, Daniela; Ragni, Guido; Persani, Luca; Arosio, M.; Beck-Peccoz, P.; Biondi, M.; Bione, S.; Bruni, V.; Brigante, C.; Cannavo`, S.; Cavallo, L.; Cisternino, M.; Colombo, I.; Corbetta, S.; Crosignani, P.G.; D'Avanzo, M.G.; Dalpra, L.; Danesino, C.; Di Battista, E.; Di Prospero, F.; Donti, E.; Einaudi, S.; Falorni, A.; Foresta, C.; Fusi, F.; Garofalo, N.; Giotti, I.; Lanzi, R.; Larizza, D.; Locatelli, N.; Loli, P.; Madaschi, S.; Maghnie, M.; Maiore, S.; Mantero, F.; Marozzi, A.; Marzotti, S.; Migone, N.; Nappi, R.; Palli, D.; Patricelli, M.G.; Pisani, C.; Prontera, P.; Petraglia, F.; Radetti, G.; Renieri, A.; Ricca, I.; Ripamonti, A.; Rossetti, R.; Russo, G.; Russo, S.; Tonacchera, M.; Toniolo, D.; Torricelli, F.; Vegetti, W.; Villa, N.; Vineis, P.; Wasniewsk, M.; Zuffardi, O.

    2012-01-01

    Primary ovarian insufficiency (POI) is a critical fertility defect characterized by an anticipated and silent impairment of the follicular reserve, but its pathogenesis is largely unexplained. The frequent maternal inheritance of POI together with a remarkable dependence of ovarian folliculogenesis upon mitochondrial biogenesis and bioenergetics suggested the possible involvement of a generalized mitochondrial defect. Here, we verified the existence of a significant correlation between blood and ovarian mitochondrial DNA (mtDNA) content in a group of women undergoing ovarian hyperstimulation (OH), and then aimed to verify whether mtDNA content was significantly altered in the blood cells of POI women. We recruited 101 women with an impaired ovarian reserve: 59 women with premature ovarian failure (POF) and 42 poor responders (PR) to OH. A Taqman copy number assay revealed a significant mtDNA depletion (P<0.001) in both POF and PR women in comparison with 43 women of similar age and intact ovarian reserve, or 53 very old women with a previous physiological menopause. No pathogenic variations in the mitochondrial DNA polymerase γ (POLG) gene were detected in 57 POF or PR women with low blood mtDNA content. In conclusion, blood cell mtDNA depletion is a frequent finding among women with premature ovarian aging, suggesting that a still undetermined but generalized mitochondrial defect may frequently predispose to POI which could then be considered a form of anticipated aging in which the ovarian defect may represent the first manifestation. The determination of mtDNA content in blood may become an useful tool for the POI risk prediction. PMID:22879975

  14. Blood cell mitochondrial DNA content and premature ovarian aging.

    PubMed

    Bonomi, Marco; Somigliana, Edgardo; Cacciatore, Chiara; Busnelli, Marta; Rossetti, Raffaella; Bonetti, Silvia; Paffoni, Alessio; Mari, Daniela; Ragni, Guido; Persani, Luca

    2012-01-01

    Primary ovarian insufficiency (POI) is a critical fertility defect characterized by an anticipated and silent impairment of the follicular reserve, but its pathogenesis is largely unexplained. The frequent maternal inheritance of POI together with a remarkable dependence of ovarian folliculogenesis upon mitochondrial biogenesis and bioenergetics suggested the possible involvement of a generalized mitochondrial defect. Here, we verified the existence of a significant correlation between blood and ovarian mitochondrial DNA (mtDNA) content in a group of women undergoing ovarian hyperstimulation (OH), and then aimed to verify whether mtDNA content was significantly altered in the blood cells of POI women. We recruited 101 women with an impaired ovarian reserve: 59 women with premature ovarian failure (POF) and 42 poor responders (PR) to OH. A Taqman copy number assay revealed a significant mtDNA depletion (P<0.001) in both POF and PR women in comparison with 43 women of similar age and intact ovarian reserve, or 53 very old women with a previous physiological menopause. No pathogenic variations in the mitochondrial DNA polymerase γ (POLG) gene were detected in 57 POF or PR women with low blood mtDNA content. In conclusion, blood cell mtDNA depletion is a frequent finding among women with premature ovarian aging, suggesting that a still undetermined but generalized mitochondrial defect may frequently predispose to POI which could then be considered a form of anticipated aging in which the ovarian defect may represent the first manifestation. The determination of mtDNA content in blood may become an useful tool for the POI risk prediction.

  15. What Will Happen After Treatment for Ovarian Cancer?

    MedlinePlus

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

  16. Premature ovarian failure

    PubMed Central

    Beck-Peccoz, Paolo; Persani, Luca

    2006-01-01

    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 <40 years, 1:10,000 women by age 20 and 1:1,000 women by age 30. The most severe forms present with absent pubertal development and primary amenorrhea (50% of these cases due to ovarian dysgenesis), whereas forms with post-pubertal onset are characterized by disappearance of menstrual cycles (secondary amenorrhea) associated with premature follicular depletion. As in the case of physiological menopause, POF presents by typical manifestations of climacterium: infertility associated with palpitations, heat intolerance, flushes, anxiety, depression, fatigue. POF is biochemically characterized by low levels of gonadal hormones (estrogens and inhibins) and high levels of gonadotropins (LH and FSH) (hypergonadotropic amenorrhea). Beyond infertility, hormone defects may cause severe neurological, metabolic or cardiovascular consequences and lead to the early onset of osteoporosis. Heterogeneity of POF is also reflected by the variety of possible causes, including autoimmunity, toxics, drugs, as well as genetic defects. POF has a strong genetic component. X chromosome abnormalities (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. PMID:16722528

  17. Paclitaxel targets VEGF-mediated angiogenesis in ovarian cancer treatment

    PubMed Central

    Ai, Bin; Bie, Zhixin; Zhang, Shuai; Li, Ailing

    2016-01-01

    Ovarian cancer is one of the gynecologic cancers with the highest mortality, wherein vascular endothelial growth factor (VEGF) is involved in regulating tumor vascularization, growth, migration, and invasion. VEGF-mediated angiogenesis in tumors has been targeted in various cancer treatments, and anti-VEGF therapy has been used clinically for treatment of several types of cancer. Paclitaxel is a natural antitumor agent in the standard front-line treatment that has significant efficiency to treat advanced cancers, including ovarian cancer. Although platinum/paclitaxel-based chemotherapy has good response rates, most patients eventually relapse because the disease develops drug resistance. We aim to review the recent advances in paclitaxel treatment of ovarian cancer via antiangiogenesis. Single-agent therapy may be used in selected cases of ovarian cancer. However, to prevent drug resistance, drug combinations should be identified for optimal effectiveness and existing therapies should be improved. PMID:27648354

  18. HER2 overexpression and amplification is present in a subset of ovarian mucinous carcinomas and can be targeted with trastuzumab therapy

    PubMed Central

    2009-01-01

    Background The response rate of ovarian mucinous carcinomas to paclitaxel/carboplatin is low, prompting interest in targeted molecular therapies. We investigated HER2 expression and amplification, and the potential for trastuzumab therapy in this histologic subtype of ovarian cancer. Methods HER2 status was tested in 33 mucinous carcinomas and 16 mucinous borderline ovarian tumors (BOT)). Five cases with documented recurrence and with tissue from the recurrence available for testing were analyzed to determine whether HER2 amplification status changed over time. Three prospectively identified recurrent mucinous ovarian carcinomas were assessed for HER2 amplification and patients received trastuzumab therapy with conventional chemotherapy. Results Amplification of HER2 was observed in 6/33 (18.2%) mucinous carcinomas and 3/16 (18.8%) BOT. HER2 amplification in primary mucinous carcinomas was not associated with an increased likelihood of recurrence. The prospectively identified recurrent mucinous carcinomas showed overexpression and amplification of HER2; one patient's tumor responded dramatically to trastuzumab in combination with conventional chemotherapy, while another patient experienced an isolated central nervous system recurrence after trastuzumab therapy. Conclusion HER2 amplification is relatively common in ovarian mucinous carcinomas (6/33, 18.2%), although not of prognostic significance. Trastuzumab therapy is a treatment option for patients with mucinous carcinoma when the tumor has HER2 amplification and overexpression. PMID:20003286

  19. Redirecting intracellular trafficking and the secretion pattern of FSH dramatically enhances ovarian function in mice

    PubMed Central

    Wang, Huizhen; Larson, Melissa; Jablonka-Shariff, Albina; Pearl, Christopher A.; Miller, William L.; Conn, P. Michael; Boime, Irving; Kumar, T. Rajendra

    2014-01-01

    FSH and luteinizing hormone (LH) are secreted constitutively or in pulses, respectively, from pituitary gonadotropes in many vertebrates, and regulate ovarian function. The molecular basis for this evolutionarily conserved gonadotropin-specific secretion pattern is not understood. Here, we show that the carboxyterminal heptapeptide in LH is a gonadotropin-sorting determinant in vivo that directs pulsatile secretion. FSH containing this heptapeptide enters the regulated pathway in gonadotropes of transgenic mice, and is released in response to gonadotropin-releasing hormone, similar to LH. FSH released from the LH secretory pathway rescued ovarian defects in Fshb-null mice as efficiently as constitutively secreted FSH. Interestingly, the rerouted FSH enhanced ovarian follicle survival, caused a dramatic increase in number of ovulations, and prolonged female reproductive lifespan. Furthermore, the rerouted FSH vastly improved the in vivo fertilization competency of eggs, their subsequent development in vitro and when transplanted, the ability to produce offspring. Our study demonstrates the feasibility to fine-tune the target tissue responses by modifying the intracellular trafficking and secretory fate of a pituitary trophic hormone. The approach to interconvert the secretory fate of proteins in vivo has pathophysiological significance, and could explain the etiology of several hormone hyperstimulation and resistance syndromes. PMID:24706813

  20. Bidirectional Estrogen-Like Effects of Genistein on Murine Experimental Autoimmune Ovarian Disease.

    PubMed

    Ding, Qiao; Wang, Yuxiao; Li, Na; Zhu, Kexue; Hu, Jielun; Wang, Sunan; Zhu, Fan; Nie, Shaoping

    2016-11-08

    This study was to investigate the bidirectional estrogen-like effects of genistein on murine experimental autoimmune ovarian disease (AOD). Female BALB/c mice were induced by immunization with a peptide from murine zona pellucida. The changes of estrous cycle, ovarian histomorphology were measured, and the levels of serum sex hormone were analyzed using radioimmunoassay. Proliferative responses of the ovary were also determined by immunohistochemistry. Administration of 25 or 45 mg/kg body weight genistein enhanced ovary development with changes in serum sex hormone levels and proliferative responses. Meanwhile, the proportions of growing and mature follicles increased and the incidence of autoimmune oophoritis decreased, which exhibited normal ovarian morphology in administration of 25 or 45 mg/kg body weight genistein, while a lower dose (5 mg/kg body weight genistein) produced the opposite effect. These findings suggest that genistein exerts bidirectional estrogen-like effects on murine experimental AOD, while a high dose (45 mg/kg body weight) of genistein may suppress AOD.

  1. Bidirectional Estrogen-Like Effects of Genistein on Murine Experimental Autoimmune Ovarian Disease

    PubMed Central

    Ding, Qiao; Wang, Yuxiao; Li, Na; Zhu, Kexue; Hu, Jielun; Wang, Sunan; Zhu, Fan; Nie, Shaoping

    2016-01-01

    This study was to investigate the bidirectional estrogen-like effects of genistein on murine experimental autoimmune ovarian disease (AOD). Female BALB/c mice were induced by immunization with a peptide from murine zona pellucida. The changes of estrous cycle, ovarian histomorphology were measured, and the levels of serum sex hormone were analyzed using radioimmunoassay. Proliferative responses of the ovary were also determined by immunohistochemistry. Administration of 25 or 45 mg/kg body weight genistein enhanced ovary development with changes in serum sex hormone levels and proliferative responses. Meanwhile, the proportions of growing and mature follicles increased and the incidence of autoimmune oophoritis decreased, which exhibited normal ovarian morphology in administration of 25 or 45 mg/kg body weight genistein, while a lower dose (5 mg/kg body weight genistein) produced the opposite effect. These findings suggest that genistein exerts bidirectional estrogen-like effects on murine experimental AOD, while a high dose (45 mg/kg body weight) of genistein may suppress AOD. PMID:27834809

  2. Ovarian Function in Samoan Women Shows Stronger Association with Signals of Energy Metabolism than Fat Reserves

    PubMed Central

    McGarvey, Stephen T.; Sesepasara, Margaret L.; Ellison, Peter T.

    2015-01-01

    Objectives The relative influence of prominent energetic hormones such as insulin and leptin on ovarian steroid production has yet to be determined and demonstrated consistently in vivo. This study reports preliminary findings on the relationship between insulin, leptin, and estradiol, a major ovarian steroid, in a sample of Samoan women. Methods Participants were 34 regularly cycling, premenopausal women in the follicular phase of their menstrual cycle with indicators of normal glucose tolerance. Fasting serum samples provided one-time, cross-sectional measures of glucose, insulin, leptin, and estradiol. Main statistical analyses consisted of Student's t-tests, used to determine significant differences in mean estradiol level between contrasting groups of insulin and leptin. Results Relatively high insulin levels within the normal range of variation showed a positive association with estradiol levels whereas relatively high leptin levels did not. The relationship between insulin and estradiol appeared to conform to a step-like categorical function -- with the highest insulin levels exerting the greatest positive effect -- rather than a dose-response linear function. Conslusions The current study adds to the growing evidence that peripheral regulation of ovarian function likely involves permissive signals that emphasize a state of energy surplus, related primarily to energy metabolism rather than energy reserves, and warrant more extensive study. PMID:24375833

  3. Randomized trial of oral cyclophosphamide and veliparib in high-grade serous ovarian, primary peritoneal, or fallopian tube cancers, or BRCA-mutant ovarian cancer

    PubMed Central

    Kummar, Shivaani; Oza, Amit M.; Fleming, Gini F.; Sullivan, Daniel M.; Gandara, David R.; Naughton, Michael J.; Villalona-Calero, Miguel A.; Morgan, Robert J.; Szabo, Peter M.; Youn, Ahrim; Chen, Alice P.; Ji, Jiuping; Allen, Deborah E.; Lih, Chih-Jian; Mehaffey, Michele G.; Walsh, William D.; McGregor, Paul M.; Steinberg, Seth M.; Williams, Paul M.; Kinders, Robert J.; Conley, Barbara A.; Simon, Richard M.; Doroshow, James H.

    2015-01-01

    Purpose Veliparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, demonstrated clinical activity in combination with oral cyclophosphamide in patients with BRCA-mutant solid tumors in a phase 1 trial. To define the relative contribution of PARP inhibition to the observed clinical activity, we conducted a randomized phase 2 trial to determine the response rate of veliparib in combination with cyclophosphamide compared to cyclophosphamide alone in patients with pretreated BRCA-mutant ovarian cancer or in patients with pretreated primary peritoneal, fallopian tube, or high-grade serous ovarian cancers (HGSOC). Methods Adult patients were randomized to receive cyclophosphamide alone (50 mg orally once daily) or with veliparib (60 mg orally once daily) in 21-day cycles. Crossover to the combination was allowed at disease progression. Results Seventy-five patients were enrolled and 72 were evaluable for response; 38 received cyclophosphamide alone and 37 the combination as their initial treatment regimen. Treatment was well tolerated. One complete response was observed in each arm, with three partial responses (PR) in the combination arm and six PRs in the cyclophosphamide alone arm. Genetic sequence and expression analyses were performed for 211 genes involved in DNA repair; none of the detected genetic alterations were significantly associated with treatment benefit. Conclusion This is the first trial that evaluated single agent, low dose cyclophosphamide in HGSOC, peritoneal, fallopian tube, and BRCA-mutant ovarian cancers. It was well tolerated and clinical activity was observed; the addition of veliparib at 60 mg daily did not improve either the response rate or the median progression free survival. PMID:25589624

  4. Gemcitabine Hydrochloride With or Without WEE1 Inhibitor MK-1775 in Treating Patients With Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

    ClinicalTrials.gov

    2017-01-31

    Ovarian Brenner Tumor; Ovarian Carcinosarcoma; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Serous Surface Papillary Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Ovarian Carcinoma

  5. Analyzing a hydrocarbon reservoir by determining the response of that reservoir to tidal forces

    SciTech Connect

    Graebner, P.

    1991-08-20

    This patent describes a method for determining a component of the response of a hydrocarbons reservoir to tidal forces. It comprises measuring a variable responsive to tidal forces within the reservoir over a measurement time period; determining a theoretical earth-tide for the reservoir over the measurement time period; and determining the component of the response to tidal forces by comparing the variable measurements and the theoretical earth-tide determinations.

  6. Ovarian stimulation using human chorionic gonadotrophin impairs blastocyst implantation and decidualization by altering ovarian hormone levels and downstream signaling in mice.

    PubMed

    Ezoe, Kenji; Daikoku, Takiko; Yabuuchi, Akiko; Murata, Nana; Kawano, Hiroomi; Abe, Takashi; Okuno, Takashi; Kobayashi, Tamotsu; Kato, Keiichi

    2014-11-01

    Ovarian stimulation induced by follicle-stimulating hormone and human chorionic gonadotrophin (hCG) is commonly used in assisted reproductive technology to increase embryo production. However, recent clinical and animal studies have shown that ovarian stimulation disrupts endometrial function and embryo development and adversely affects pregnancy outcomes. How ovarian stimulation impairs pregnancy establishment and the precise mechanisms by which this stimulation reduces the chances of conception remain unclear. In this study, we first demonstrated that ovarian stimulation using hCG alone impairs implantation, decidualization and fetal development of mice by generating abnormal ovarian hormone levels. We also showed that ovarian hormone levels were altered because of changes in the levels of the enzymes involved in their synthesis in the follicles and corpora lutea. Furthermore, we determined that anomalous ovarian hormone secretion induced by ovarian stimulation alters the spatiotemporal expression of progesterone receptors and their downstream genes, especially in the uterine epithelium. Epithelial estrogenic signaling and cell proliferation were promoted on the day of implantation in stimulated mice and these changes led to the failure of uterine transition from the prereceptive to the receptive state. Collectively, our findings indicate that ovarian stimulation using hCG induces an imbalance in steroid hormone secretion, which causes a failure of the development of uterine receptivity and subsequent implantation and decidualization by altering the expression of steroid receptors and their downstream signaling associated with embryo implantation.

  7. Cisplatin induces stemness in ovarian cancer

    PubMed Central

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

    2016-01-01

    The mainstay of treatment for ovarian cancer is platinum-based cytotoxic chemotherapy. However, therapeutic resistance and recurrence is a common eventuality for nearly all ovarian cancer patients, resulting in poor median survival. Recurrence is postulated to be driven by a population of self-renewing, therapeutically resistant cancer stem cells (CSCs). A current limitation in CSC studies is the inability to interrogate their dynamic changes in real time. Here we utilized a GFP reporter driven by the NANOG-promoter to enrich and track ovarian CSCs. Using this approach, we identified a population of cells with CSC properties including enhanced expression of stem cell transcription factors, self-renewal, and tumor initiation. We also observed elevations in CSC properties in cisplatin-resistant ovarian cancer cells as compared to cisplatin-naïve ovarian cancer cells. CD49f, a marker for CSCs in other solid tumors, enriched CSCs in cisplatin-resistant and -naïve cells. NANOG-GFP enriched CSCs (GFP+ cells) were more resistant to cisplatin as compared to GFP-negative cells. Moreover, upon cisplatin treatment, the GFP signal intensity and NANOG expression increased in GFP-negative cells, indicating that cisplatin was able to induce the CSC state. Taken together, we describe a reporter-based strategy that allows for determination of the CSC state in real time and can be used to detect the induction of the CSC state upon cisplatin treatment. As cisplatin may provide an inductive stress for the stem cell state, future efforts should focus on combining cytotoxic chemotherapy with a CSC targeted therapy for greater clinical utility. PMID:27105520

  8. Determination of the magnetostrictive response of nanoparticles via magnetoelectric measurements.

    PubMed

    Martins, P; Silva, M; Lanceros-Mendez, S

    2015-06-07

    It is successfully demonstrated that nanoparticle's magnetostriction can be accurately determined based on the magnetoelectric effect measured on polymeric composite materials. This represents a novel, simple and versatile method for the determination of particle's magnetostriction at the nano scale and in their dispersed state, which has been, up to now, a difficult and imprecise task.

  9. Induction of apoptosis in ovarian carcinoma cells by AHPN/CD437 is mediated by retinoic acid receptors.

    PubMed

    Holmes, W F; Dawson, M I; Soprano, R D; Soprano, K J

    2000-10-01

    Retinoids have great promise in the area of cancer therapy and chemoprevention. These natural and synthetic derivatives of vitamin A have been shown to play an important role in regulating cell differentiation and proliferation. While all-trans-retinoic acid (ATRA) has been demonstrated to inhibit the growth of several ovarian tumor cell lines, other ovarian carcinoma cell lines have been found to be resistant to retinoid dependent growth suppression. Interestingly, a novel synthetic retinoid, CD437 or AHPN, has been demonstrated to inhibit the growth of both ATRA-sensitive (CA-OV3) and ATRA-resistant (SK-OV3) ovarian tumor cell lines as well as to induce apoptosis. The overall goal of this research was to understand the mechanism by which AHPN/CD437 induces apoptosis in ovarian tumor cell lines. Since a number of studies have demonstrated the importance of nuclear receptors (RARs and RXRs) in mediating cellular responses to retinoids, we wished to determine the role of RARs in mediating the AHPN/CD437 response. We modulated RAR level and function by overexpressing either wild type RAR-gamma or a pan dominant negative mutant of all RAR subtypes called RAR-beta (R269Q), or through the use of an RAR-gamma antagonist, MM11253. We found that inhibition of RAR function reduced but did not eliminate induction of apoptosis in both CA-OV3 and SK-OV3 cells by AHPN/CD437. Likewise, overexpression of wild type RAR-gamma was found to increase apoptosis after treatment with AHPN/CD437. Our results suggest that in ovarian carcinomas, AHPN/CD437 induced apoptosis is mediated at least in part via an RAR pathway.

  10. Determinants of early life immune responses to RSV infection.

    PubMed

    Ruckwardt, Tracy J; Morabito, Kaitlyn M; Graham, Barney S

    2016-02-01

    Respiratory syncytial virus causes significant morbidity and mortality in both developed and developing countries, and a vaccine that adequately protects from severe disease remains an important unmet need. RSV disease has an inordinate impact on the very young, and the physical and immunological immaturity of early life complicates vaccine design. Defining and targeting the functional capacities of early life immune responses and controlling responses during primary antigen exposure with selected vaccine delivery approaches will be important for protecting infants by active immunization. Alternatively, vaccination of older children and pregnant mothers may ameliorate disease burden indirectly until infants reach about six months of age, when they can generate more effective anti-RSV immune responses.

  11. Executive Impairment Determines ADHD Medication Response: Implications for Academic Achievement

    ERIC Educational Resources Information Center

    Hale, James B.; Reddy, Linda A.; Semrud-Clikeman, Margaret; Hain, Lisa A.; Whitaker, James; Morley, Jessica; Lawrence, Kyle; Smith, Alex; Jones, Nicole

    2011-01-01

    Methylphenidate (MPH) often ameliorates attention-deficit/hyperactivity disorder (ADHD) behavioral dysfunction according to "indirect" informant reports and rating scales. The standard of care behavioral MPH titration approach seldom includes "direct" neuropsychological or academic assessment data to determine treatment…

  12. Poor ovarian reserve

    PubMed Central

    Jirge, Padma Rekha

    2016-01-01

    Poor ovarian reserve (POR) is an important limiting factor for the success of any treatment modality for infertility. It indicates a reduction in quantity and quality of oocytes in women of reproductive age group. It may be age related as seen in advanced years of reproductive life or may occur in young women due to diverse etiological factors. Evaluating ovarian reserve and individualizing the therapeutic strategies are very important for optimizing the success rate. Majority or women with POR need to undergo in vitro fertilization to achieve pregnancy. However, pregnancy rate remains low despite a plethora of interventions and is associated with high pregnancy loss. Early detection and active management are essential to minimize the need for egg donation in these women. PMID:27382229

  13. Visual Flight Feedback as a Determiner of Motor Response Recognition

    ERIC Educational Resources Information Center

    Newell, K. M.

    1975-01-01

    In this study, over a series of learning trials of projecting a ball a criterion distance, the hypotheses were tested and confirmed that withdrawal of visual feedback of the flight of the ball would produce a decrement in response recognition but not recall. (JS)

  14. 40 CFR 1065.845 - Response factor determination.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ....845 Section 1065.845 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR POLLUTION CONTROLS ENGINE-TESTING PROCEDURES Testing With Oxygenated Fuels § 1065.845 Response factor... zero and span balance gases may be any combination of purified air or purified nitrogen that meets...

  15. 40 CFR 1065.845 - Response factor determination.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ....845 Section 1065.845 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR POLLUTION CONTROLS ENGINE-TESTING PROCEDURES Testing With Oxygenated Fuels § 1065.845 Response factor... zero and span balance gases may be any combination of purified air or purified nitrogen that meets...

  16. 40 CFR 1065.845 - Response factor determination.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ....845 Section 1065.845 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR POLLUTION CONTROLS ENGINE-TESTING PROCEDURES Testing With Oxygenated Fuels § 1065.845 Response factor... zero and span balance gases may be any combination of purified air or purified nitrogen that meets...

  17. 40 CFR 1065.845 - Response factor determination.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ....845 Section 1065.845 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR POLLUTION CONTROLS ENGINE-TESTING PROCEDURES Testing With Oxygenated Fuels § 1065.845 Response factor... that FID zero and span balance gases may be any combination of purified air or purified nitrogen...

  18. 40 CFR 1065.845 - Response factor determination.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ....845 Section 1065.845 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR POLLUTION CONTROLS ENGINE-TESTING PROCEDURES Testing With Oxygenated Fuels § 1065.845 Response factor... zero and span balance gases may be any combination of purified air or purified nitrogen that meets...

  19. Determinants of Coping Responses among Mexican American Adolescents.

    ERIC Educational Resources Information Center

    Guinn, Bobby; Vincent, Vern

    2002-01-01

    Examined the relationship of perceived stress, self-esteem, acculturation, and gender to the coping response of Mexican American adolescents. Data from self-report surveys indicated that adolescents had relatively high perceived stress levels, low acculturation, and a moderate self-esteem, with no significant gender differences. Self-esteem was…

  20. Contextual Determinants of Achievement Responses in Men and Women.

    ERIC Educational Resources Information Center

    Albino, Judith E.; Shuell, Thomas J.

    Picture stimuli depicting females and males working together were shown to college students by either a male or a female experimenter. Subjects' responses to the pictures were assessed using standard need achievement scoring. A significant interaction was obtained between sex of subject and sex of experimenter, such that higher need achievement…

  1. [Cryopreservation of ovarian tissue].

    PubMed

    Aubard, Y; Poirot, C; Piver, P

    2002-05-01

    Ovarian tissue cryopreservation (OTCP) is a new procedure of medically assisted procreation, still at the experimental stage, whose primary aim is to store female gametes as sperm cryopreservation permits to do for male gametes. Ovarian tissue is removed very simply by laparoscopy. It survives well to freezing if the medium contains a cryoprotective agent and the rate of freezing is slow. In contrast, thawing must be rapid. There are three processes for the utilization of ovarian tissue after thawing. In vitro maturation and xenografting remain impossible for technical and ethical reasons. Autologous transplantation (orthotopic or heterotopic) of the tissue is therefore the only foreseeable method over the short term. Indications for OTCP must remain rare as long as no pregnancy has been obtained in human. At the present time, only female patients who would inevitably suffer the loss of their fertility should be able to take advantage of OTCP. Basically, this would mean women subjected to castrating anticancer therapy. It would seem reasonable to set the age limit at 35-years for carrying out OTCP. Lastly, female patients should be clearly informed that the method is still at the research stage, and in France samples must be taken in accordance with the laws governing clinical research.

  2. Antigen-specific immunotherapy of cervical and ovarian cancer

    PubMed Central

    Hung, Chien-fu; Wu, TC; Monie, Archana; Roden, Richard

    2009-01-01

    Summary We contrast the efforts to treat ovarian cancer and cervical cancer through vaccination because of their different pathobiology. A plethora of approaches have been developed for therapeutic vaccination against cancer, many of which target defined tumor-associated antigens (TAAs). Persistent infection with oncogenic human papillomavirus (HPV) types is necessary cause of cervical cancer. Furthermore, cervical cancer patients frequently mount both humoral and T cell immune responses to the HPV E6 and E7 oncoproteins, whose expression is required for the transformed phenotype. Numerous vaccine studies target these viral TAAs, including recent trials that may enhance clearance of pre-malignant disease. By contrast little is known about the etiology of epithelial ovarian cancer. Although it is clear that p53 mutation or loss is a critical early event in the development of epithelial ovarian cancer, no precursor lesion has been described for the most common serous histotype, and even the location of its origin is debated. These issues have complicated the selection of appropriate ovarian TAAs and the design of vaccines. Here we focus on mesothelin as a promising ovarian TAA because it is overexpressed and immunogenic at high frequency in patients, is displayed on the cell surface and potentially contributes to ovarian cancer biology. PMID:18363994

  3. Pathway modulations and epigenetic alterations in ovarian tumorbiogenesis

    PubMed Central

    Saldanha, Sabita N.; Tollefsbol, Trygve O.

    2013-01-01

    Cellular pathways are numerous and are highly integrated in function in the control of cellular systems. They collectively regulate cell division, proliferation, survival and apoptosis of cells and mutagenesis of key genes that control these pathways can initiate neoplastic transformations. Understanding these pathways is crucial to future therapeutic and preventive strategies of the disease. Ovarian cancers are of three major types; epithelial, germ-cell and stromal. However, ovarian cancers of epithelial origin, arising from the mesothelium, are the predominant form. Of the subtypes of ovarian cancer, the high-grade serous tumors are fatal, with low survival rate due to late detection and poor response to treatments. Close examination of preserved ovarian tissues and in vitro studies have provided insights into the mechanistic changes occurring in cells mediated by a few key genes. This review will focus on pathways and key genes of the pathways that are mutated or have aberrant functions in the pathology of ovarian cancer. Non-genetic mechanisms that are gaining prominence in the pathology of ovarian cancer, miRNAs and epigenetics, will also be discussed in the review. PMID:24105793

  4. Expression of PCV2 antigen in the ovarian tissues of gilts

    PubMed Central

    TUMMARUK, Padet; PEARODWONG, Pachara

    2015-01-01

    The present study was performed to determine the expression of porcine circovirus type 2 (PCV2) antigen in the ovarian tissue of naturally infected gilts. Ovarian tissues were obtained from 11 culled gilts. The ovarian tissues sections were divided into two groups according to PCV2 DNA detection using PCR. PCV2 antigen was assessed in the paraffin embedded ovarian tissue sections by immunohistochemistry. A total of 2,131 ovarian follicles (i.e., 1,437 primordial, 133 primary, 353 secondary and 208 antral follicles), 66 atretic follicles and 131 corpora lutea were evaluated. It was found that PCV2 antigen was detected in 280 ovarian follicles (i.e., 239 primordial follicles, 12 primary follicles, 10 secondary follicles and 19 antral follicles), 1 atretic follicles and 3 corpora lutea (P<0.05). PCV2 antigen was detected in primordial follicles more often than in secondary follicles, atretic follicles and corpora lutea (P<0.05). The detection of PCV2 antigen was found mainly in oocytes. PCV2 antigen was found in both PCV2 DNA positive and negative ovarian tissues. It can be concluded that PCV2 antigen is expressed in all types of the ovarian follicles and corpora lutea. Further studies should be carried out to determine the influence of PCV2 on porcine ovarian function and oocyte quality. PMID:26522687

  5. Dietary supplementation of yucca (Yucca schidigera) affects ovine ovarian functions.

    PubMed

    Vlčková, Radoslava; Sopková, Drahomíra; Andrejčáková, Zuzana; Valocký, Igor; Kádasi, Attila; Harrath, Abdel Halim; Petrilla, Vladimír; Sirotkin, Alexander V

    2017-01-15

    Yucca (Yucca schidigera) is a popular medicinal plant due to its many positive effects on animal and human physiology, including their reproductive systems. To examine the effect of supplemental yucca feeding on sheep reproduction, including ovarian functions and their hormonal regulators, ewes were fed (or not fed, control) yucca powder (1.5 g/head/day, 30 days). Macromorphometric indexes of the oviduct, ovary, and ovarian folliculogenesis were measured. Reproductive hormone levels in the blood were measured using a radioimmunoassay. Granulosa cells were aspirated from the ovary, and their proliferation and apoptosis were detected using immunocytochemistry. To assess secretory activity and its response to gonadotropin, ovarian fragments of treated and control ewes were cultured with and without follicle-stimulating hormone (FSH; 0, 0.1, 1, 10, or 100 IU/mL), and the release of reproductive hormones into the culture medium was evaluated. Finally, to examine the direct action of yucca on the ovary, ovarian fragments from control ewes were cultured with and without yucca extract (1, 10, or 100 μg/mL), and the release of reproductive hormones was measured. Yucca supplementation significantly decreased the size of small antral follicles (2 to <5 mm in diameter), increased accumulation of the apoptosis marker bax, and decreased serum progesterone (P4) and estradiol (E2) levels. It inhibited the release of P4 (but not other hormones), to prevent the stimulatory action of FSH on P4 output and promoted insulin-like growth factor I (IGF-I) release by fragments cultured with FSH. However, yucca supplementation did not affect the size of larger follicles and number of follicles, volume and weight of ovaries, length and weight of oviducts, caspase 3 accumulation, cell proliferation, testosterone (T) or IGF-I serum levels, or T or E2 release by cultured ovarian fragments and their response to FSH. Yucca addition to culture medium inhibited P4 and IGF-I, but not T or E2

  6. Cellular therapy for ovarian cancer: experimental and clinical perspectives.

    PubMed

    Ingersoll, Susan B; Ahmad, Sarfraz; Finkler, Neil J; Edwards, John R; Holloway, Robert W

    2012-01-01

    Ovarian cancer is the leading cause of death among gynecologic malignancies and the 5th leading cause of cancer deaths for women in the United States. Two-thirds of patients present with advanced-stage disease (Stage III and IV) and the majority will suffer recurrence of disease, require ongoing treatment, and eventually succumb to chemotherapy-resistant disease. To potentially circumvent chemo-resistance in recurrent ovarian cancer, immunotherapy is being explored as a novel treatment option. Our laboratory findings demonstrate that immune effector cells from healthy donors elicit a significant cytotoxic response in the presence of IL-2 and IFN alpha- 2b against ovarian cancer in vitro; however, peripheral blood mononuclear cells (PBMC) isolated from ovarian cancer patients fail to elicit a similar response. A major obstacle to immunotherapy is the immunosuppressive environment supported by tumors, which limits the immune system's ability to fight the tumor. Myeloid-derived suppressor cells are an immature population of myeloid cells, which have recently been implicated to play a major role in immunosuppression and tumor evasion. In addition to novel immunotherapies, new diagnostic and prognostic markers are being identified through applying molecular tools/approaches in clinical and pathological analyses of this malignancy, which will provide additional therapeutic targets. To test these experimental therapeutic options, pre-clinical murine models of ovarian cancer are being developed. Ultimately, treatment of ovarian cancer will benefit from the careful alignment of appropriate target, drug, patient, and trial design. This article provides an objective overview of cellular therapy (the use of immune cells to elicit an anti-tumor response) for ovarian cancer highlighting both experimental and clinical perspectives.

  7. [Genetic aspects of premature ovarian failure].

    PubMed

    Warenik-Szymankiewicz, Alina; Słopień, Radosław

    2005-01-01

    Among the causes of premature ovarian failure (POF) two groups of factors are reported: factors which lead to decrease of follicular number and factors which stimulate follicular atresia. In the first group genetic factors are the most important whereas in the second: enzymatic autoimmunological, iatrogenic, toxins and infections are reported. In 1986 familiar POF on the background of long arm of chromosome X deletion was reported. Other chromosomes which are important for normal ovarian function are: chromosome 21 (AIRE gene), chromosome 11 (gene of beta FSH, ATM gene), chromosome 3 (gene responsible for BEPS syndrome) and chromosome 2 (genes of FSH and LH receptors). In this review the role of these genes and results of several epidemiological studies are reported.

  8. Moving beyond Technological Determinism and Autonomy to Face Our Responsibilities

    ERIC Educational Resources Information Center

    Vanderburg, Willem H.

    2012-01-01

    This article shows that technological neutrality, determinism, and autonomy correspond to parts of a spectrum of possible historical relations between societies and their technologies. The spectrum of relations is based on the recognition that as we change technology, technology simultaneously changes us. This reinterpretation compels us to face…

  9. Ovarian differentiation and development in cachara Pseudoplatystoma fasciatum.

    PubMed

    Valentin, F N; Batlouni, S R; Nascimento, N F; Silva, R C; Manzini, B; Hilbig, C C; Pereira-Santos, M; Nakaghi, L S O

    2016-07-01

    One thousand five hundred cachara or tiger shovelnose catfish Pseudoplatystoma fasciatum, obtained from induced reproduction, were used to determine the onset of ovarian differentiation and development and to record the main characteristics of this process. Samples were collected from 0 to 240 days post-fertilization (dpf) and the results classified into stages I-XII. Ovarian formation was histologically detected for the first time when juveniles measured mean ± s.d. 51·5 ± 8·3 mm total length (LT ) at 39-45 dpf (stages I-V), with intense somatic cell proliferation originating in the ovarian cavity. Both LT and age of fish had a positive correlation (P < 0·001) with ovarian differentiation, but LT showed a greater correlation (r(2)  = 0·95) than age (r(2)  = 0·85), especially during the initial stages of development. From stages VI to VII, the ovarian cavity was enlarged and undifferentiated oogonia were present. At stage VIII, small projections formed in the ovarian stroma towards the ventral region of the gonad (future ovarian lamellae) and the basal membrane and differentiated oogonia nests could be seen. At stages IX and X, the germ cells entered meiosis and folliculogenesis was completed by stages XI and XII, which can be considered late in comparison to other Siluriformes. This study has demonstrated that ovarian differentiation in P. fasciatum begins with an intense proliferation of squamous epithelial cells (somatic cells) during the early stages of development and that sex inversion protocols could, thus, be applied successfully before this period. Furthermore, the results have demonstrated that both size and age can influence gonad differentiation and development in this species.

  10. Advancing ovarian folliculometry with selective plane illumination microscopy

    PubMed Central

    Lin, Hsiao-Chun Amy; Dutta, Rahul; Mandal, Subhamoy; Kind, Alexander; Schnieke, Angelika; Razansky, Daniel

    2016-01-01

    Determination of ovarian status and follicle monitoring are common methods of diagnosing female infertility. We evaluated the suitability of selective plane illumination microscopy (SPIM) for the study of ovarian follicles. The large field of view and fast acquisition speed of our SPIM system enables rendering of volumetric image stacks from intact whole porcine ovarian follicles, clearly visualizing follicular features including follicle volume and average diameter (70 μm–2.5 mm), their spherical asymmetry parameters, size of developing cumulus oophorus complexes (40 μm–110 μm), and follicular wall thickness (90 μm–120 μm). Follicles at all developmental stages were identified. A distribution of the theca thickness was measured for each follicle, and a relationship between these distributions and the stages of follicular development was discerned. The ability of the system to non-destructively generate sub-cellular resolution 3D images of developing follicles, with excellent image contrast and high throughput capacity compared to conventional histology, suggests that it can be used to monitor follicular development and identify structural abnormalities indicative of ovarian ailments. Accurate folliculometric measurements provided by SPIM images can immensely help the understanding of ovarian physiology and provide important information for the proper management of ovarian diseases. PMID:27905503

  11. Advancing ovarian folliculometry with selective plane illumination microscopy

    NASA Astrophysics Data System (ADS)

    Lin, Hsiao-Chun Amy; Dutta, Rahul; Mandal, Subhamoy; Kind, Alexander; Schnieke, Angelika; Razansky, Daniel

    2016-12-01

    Determination of ovarian status and follicle monitoring are common methods of diagnosing female infertility. We evaluated the suitability of selective plane illumination microscopy (SPIM) for the study of ovarian follicles. The large field of view and fast acquisition speed of our SPIM system enables rendering of volumetric image stacks from intact whole porcine ovarian follicles, clearly visualizing follicular features including follicle volume and average diameter (70 μm–2.5 mm), their spherical asymmetry parameters, size of developing cumulus oophorus complexes (40 μm–110 μm), and follicular wall thickness (90 μm–120 μm). Follicles at all developmental stages were identified. A distribution of the theca thickness was measured for each follicle, and a relationship between these distributions and the stages of follicular development was discerned. The ability of the system to non-destructively generate sub-cellular resolution 3D images of developing follicles, with excellent image contrast and high throughput capacity compared to conventional histology, suggests that it can be used to monitor follicular development and identify structural abnormalities indicative of ovarian ailments. Accurate folliculometric measurements provided by SPIM images can immensely help the understanding of ovarian physiology and provide important information for the proper management of ovarian diseases.

  12. 33 CFR 133.23 - Investigation to determine the source and responsible party.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL LIABILITY TRUST FUND; STATE ACCESS § 133.23 Investigation to determine the source and...

  13. 33 CFR 133.23 - Investigation to determine the source and responsible party.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL LIABILITY TRUST FUND; STATE ACCESS § 133.23 Investigation to determine the source and...

  14. 33 CFR 133.23 - Investigation to determine the source and responsible party.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL LIABILITY TRUST FUND; STATE ACCESS § 133.23 Investigation to determine the source and...

  15. 33 CFR 133.23 - Investigation to determine the source and responsible party.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL LIABILITY TRUST FUND; STATE ACCESS § 133.23 Investigation to determine the source and...

  16. 33 CFR 133.23 - Investigation to determine the source and responsible party.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL LIABILITY TRUST FUND; STATE ACCESS § 133.23 Investigation to determine the source and...

  17. Urinary microRNA-30a-5p is a potential biomarker for ovarian serous adenocarcinoma.

    PubMed

    Zhou, Jun; Gong, Guanghui; Tan, Hong; Dai, Furong; Zhu, Xin; Chen, Yile; Wang, Junpu; Liu, Ying; Chen, Puxiang; Wu, Xiaoying; Wen, Jifang

    2015-06-01

    MicroRNAs (miRNAs) can serve as biomarkers in human cancer. To determine the clinical value of urinary miRNAs for ovarian serous adenocarcinoma, we collected urine samples from 39 ovarian serous adenocarcinoma patients, 26 patients with benign gynecological disease and 30 healthy controls. The miRNA microarray data showed that only miR-30a-5p was upregulated and 37 miRNAs were downregulated in the urine samples of ovarian serous adenocarcinoma patients, when compared to healthy controls, which was confirmed after conducting quantitative PCR. The upregulation of urinary miR-30a-5p was closely associated with early stage of ovarian serous adenocarcinoma as well as lymphatic metastasis. Receiver operator characteristic (ROC) analysis demonstrated the potential use of urinary miR-30a-5p as a diagnostic marker for ovarian serous adenocarcinoma. Furthermore, a lower urine level of miR-30a-5p was found in 20 gastric cancer and 20 colon carcinoma patients when compared to ovarian serous adenocarcinoma, suggesting that the upregulation of urinary miR-30a-5p may be specific for ovarian serous adenocarcinoma. miR-30a-5p was also upregulated in ovarian serous adenocarcinoma tissues and cell lines, while urinary miR-30a-5p from ovarian cancer patients was notably reduced following the surgical removal of ovarian serous adenocarcinoma, suggesting that urinary miR-30a-5p was derived from the ovarian serous adenocarcinoma tissue. Notably, miR-30a-5p was concentrated with exosomes from the ovarian cancer cell supernatant or urine from ovarian serous adenocarcinoma patients, supporting a pathway for excretion into the urine. The results also showed that the knockdown of miR-30a-5p significantly inhibited the proliferation and migration of ovarian cancer cells. In summary, to the best of our knowledge, the present study provided the first evidence of increased miR-30a-5p in the urine of ovarian serous adeno-carcinoma patients, while the inhibition of miR-30a-5p suppressed the

  18. A6 in Treating Patients With Persistent or Recurrent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2015-02-27

    Fallopian Tube Carcinoma; Malignant Ovarian Mixed Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Primary Peritoneal Carcinoma; Recurrent Ovarian Carcinoma; Undifferentiated Ovarian Carcinoma

  19. Ovarian function and reproductive senescence in the rat: role of ovarian sympathetic innervation.

    PubMed

    Cruz, Gonzalo; Fernandois, Daniela; Paredes, Alfonso H

    2017-02-01

    Successful reproduction is the result of a myriad interactions in which the ovary and the ovarian follicular reserve play a fundamental role. At present, women who delay maternity until after 30 years of age have a decreased fertility rate due to various causes, including damaged follicles and a reduction in the reserve pool of follicles. Therefore, the period just prior to menopause, also known as the subfertile period, is important. The possibility of modulating the follicular pool and the health of follicles during this period to improve fertility is worth exploring. We have developed an animal model to study the ovarian ageing process during this subfertile period to understand the mechanisms responsible for reproductive senescence. In the rat model, we have shown that the sympathetic nervous system participates in regulating the follicular development during ovarian ageing. This article reviews the existing evidence on the presence and functional role of sympathetic nerve activity in regulating the follicular development during ovarian ageing, with a focus on the subfertile period.Free Spanish abstract: A Spanish translation of this abstract is freely available at http://www.reproduction-online.org/content/153/2/R61/suppl/DC1.

  20. Determining and Modeling the Response of Ytterbium Piezoresistance Transducers.

    DTIC Science & Technology

    1986-05-01

    15. -* A 11 B. Presentations The following invited talks, based in part on the AFOSR work, were presented by the principal investigator 1. "Can...supported in part by AFOSR, were presented at scientific meetings as indicated: 1. S. C. Gupta and Y. L Gupta, "Response of Ytterbium Foils Oriented...Postdoctoral Research Associates have been supported in part during the course of this grant. "I.’ I. Dr. S. C. Gupta (Ph.D. in Physics from the University of

  1. How Is Ovarian Cancer Diagnosed?

    MedlinePlus

    ... are not used often to look for ovarian cancer. MRI scans are particularly helpful to examine the brain and spinal cord. MRI scans take longer than CT scans, -- often up to 30 minutes or more. Also, you have to be placed inside ... whether ovarian cancer has spread (metastasized) to the lungs. This spread ...

  2. Estradiol release kinetics determine tissue response in ovariectomized rats.

    PubMed

    Otto, Christiane; Kantner, Ingrid; Nubbemeyer, Reinhard; Schkoldow, Jenny; Fuchs, Iris; Krahl, Elisabeth; Vonk, Richardus; Schüler, Christiane; Fritzemeier, Karl-Heinrich; Erben, Reinhold G

    2012-04-01

    Estrogen replacement is an effective therapy of postmenopausal symptoms such as hot flushes, bone loss, and vaginal dryness. Undesired estrogen effects are the stimulation of uterine and mammary gland epithelial cell proliferation as well as hepatic estrogenicity. In this study, we examined the influence of different estradiol release kinetics on tissue responsivity in ovariectomized (OVX) rats. Pulsed release kinetics was achieved by ip or sc administration of estradiol dissolved in physiological saline containing 10% ethanol (EtOH/NaCl) whereas continuous release kinetics was achieved by sc injection of estradiol dissolved in benzylbenzoate/ricinus oil (1+4, vol/vol). Initial 3-d experiments in OVX rats showed that pulsed ip estradiol administration had profoundly reduced stimulatory effects on the uterus and the liver compared with continuous release kinetics. On the other hand, both administration forms prevented severe vaginal atrophy. Based on these results, we compared the effects of pulsed (sc in EtOH/NaCl) vs. continuous (sc in benzylbenzoate/ricinus oil) estradiol release kinetics on bone, uterus, mammary gland, and liver in a 4-month study in OVX rats. Ovariectomy-induced bone loss was prevented by both administration regimes. However, pulsed estradiol resulted in lower uterine weight, reduced induction of hepatic gene expression, and reduced mammary epithelial hyperplasia relative to continuous estradiol exposure. We conclude that organ responsivity is influenced by different hormone release kinetics, a fact that might be exploited to reduce undesired estradiol effects in postmenopausal women.

  3. Ecological genomics in Daphnia: stress responses and environmental sex determination.

    PubMed

    Eads, B D; Andrews, J; Colbourne, J K

    2008-02-01

    Ecological genomics is the study of adaptation of natural populations to their environment, and therefore seeks to link organism and population level processes through an understanding of genome organization and function. The planktonic microcrustacean Daphnia, which has long been an important system for ecology, is now being used as a genomic model as well. Here we review recent progress in selected areas of Daphnia genomics research. Production of parthenogenetic male offspring occurs through environmental cues, which clearly involves endocrine regulation and has also been studied as a toxicological response to juvenoid hormone analog insecticides. Recent progress has uncovered a putative juvenoid cis-response element, which together with microarray analysis will stimulate further research into nuclear hormone receptors and their associated transcriptional regulatory networks. Ecotoxicological studies indicate that mRNA profiling is a sensitive and specific research tool with promising applications in environmental monitoring and for uncovering conserved cellular processes. Rapid progress is expected to continue in these and other areas, as genomic tools for Daphnia become widely available to investigators.

  4. Delayed childbearing: determining responsibilities for prime gamete quality.

    PubMed

    Campagne, Daniel M

    2013-01-01

    Delayed parenting affects fertility in women and in men, and cryopreservation of oocytes and sperm is becoming the latest trend as a solution for those who want or need to postpone procreation, in an attempt to avoid the damage medical conditions or time itself produces in gametes. Although "social freezing" is considered legitimate, its ethical and social aspects are in need of an overdue medical, public and legal debate. Assisted reproduction and cryopreservation, in combination with womb outsourcing, have opened the door to biological ectogenesis and the subsequent question of whether delayed childbearing means we should formally separate procreation from sexual activity. This article briefly summarizes what cryotechniques are capable of presently and in the near future, to separate fact from fiction. It names the implications for and discusses the practically virgin subject of the underlying responsibilities of delayed parenting techniques towards the child-to-be-not only the unborn but also the not-yet-conceived child. Considering the medical, economic, legal and social consequences of these rapidly growing developments in reproduction, several reasons point at the need to formally separate procreation from sexual activity, specifying responsibilities in the first while respecting personal choice in the second.

  5. Response Audit of an Internet Survey of Health Care Providers and Administrators: Implications for Determination of Response Rates

    PubMed Central

    Orchard, Margo C; Golden, Brian; Holowaty, Eric; Paszat, Lawrence; Brown, Adalsteinn D; Sullivan, Terrence

    2008-01-01

    Background Internet survey modalities often compare unfavorably with traditional survey modalities, particularly with respect to response rates. Response to Internet surveys can be affected by the distribution options and response/collection features employed as well as the existence of automated (out-of-office) replies, automated forwarding, server rejection, and organizational or personal spam filters. However, Internet surveys also provide unparalleled opportunities to track study subjects and examine many of the factors influencing the determination of response rates. Tracking data available for Internet surveys provide detailed information and immediate feedback on a significant component of response that other survey modalities cannot match. This paper presents a response audit of a large Internet survey of more than 5000 cancer care providers and administrators in Ontario, Canada. Objective Building upon the CHEcklist for Reporting Results of Internet E-Surveys (CHERRIES), the main objectives of the paper are to (a) assess the impact of a range of factors on the determination of response rates for Internet surveys and (b) recommend steps for improving published descriptions of Internet survey methods. Methods We audited the survey response data, analyzing the factors that affected the numerator and denominator in the ultimate determination of response. We also conducted a sensitivity analysis to account for the inherent uncertainty associated with the impact of some of the factors on the response rates. Results The survey was initially sent out to 5636 health care providers and administrators. The determination of the numerator was influenced by duplicate/unattached responses and response completeness. The numerator varied from a maximum of 2031 crude (unadjusted) responses to 1849 unique views, 1769 participants, and 1616 complete responses. The determination of the denominator was influenced by forwarding of the invitation email to unknown individuals

  6. Which Should Be the Preferred Technique During Laparoscopic Ovarian Cystectomy.

    PubMed

    Sahin, Cagdas; Akdemir, Ali; Ergenoglu, Ahmet Mete; Ozgurel, Banu; Yeniel, Ahmet Ozgur; Taskiran, Dilek; Sendag, Fatih

    2017-03-01

    The aim of the present study was to determine the long-term effects of different laparoscopic hemostatic techniques on ovarian reserve after ovarian cystectomy. Ninety patients with unilateral ovarian cysts were recruited and randomly distributed into 2 groups. Laparoscopic stripping cystectomy was performed in all patients. Afterward, cystectomy hemostasis was achieved via hemostatic suture or bipolar electrocoagulation. Serum levels of anti-Müllerian hormone (AMH) were determined preoperatively and postoperatively at 1, 3, and 12 months, and patients were evaluated for residual ovarian volume, antral follicle count, and pregnancy. The statistical difference was determined between the 2 groups in terms of AMH levels at 3 months (hemostatic suture group = 3.17 ± 3.40 vs bipolar electrocoagulation group = 2.38 ± 2.57, P = .006) and 12 months (hemostatic suture group = 3.71 ± 3.09 vs bipolar electrocoagulation group = 2.78 ± 2.85, P = .005). In addition, in the hemostatic suture group, there was no statistically significant difference between preoperative and postoperative AMH levels ( P = .165) and between the postoperative antral follicle count ( P = .779) and the residual ovarian volume ( P = .248), whereas in the bipolar electrocoagulation group, postoperative AMH levels were lower than preoperative levels ( P = .028) and postoperative residual ovarian volumes at 3 and 12 months were lower than those at 1 month ( P = .001). Nonetheless, pregnancy rates were not significantly different ( P = .546). Bipolar electrocoagulation is more destructive compared with hemostatic suture. However, the ovarian reserve does not decrease further during the follow-up period.

  7. Biological Basis for Chemoprevention of Ovarian Cancer

    DTIC Science & Technology

    2001-10-01

    Prevention may represent a feasible approach to decreasing ovarian cancer mortality . To achieve a better understanding of the etiology of ovarian...Progestins have a potent apoptotic effect on ovarian epithelial cells and we have shown that levonorgestrel dramatically decreases ovarian cancer incidence...effective chemoprevention strategies that might decrease mortality from this disease.

  8. Ixabepilone and Liposomal Doxorubicin in Advanced Ovarian Cancer

    ClinicalTrials.gov

    2016-02-11

    Fallopian Tube Cancer; Female Reproductive Cancer; Recurrent Breast Cancer; Recurrent Ovarian Epithelial Cancer; Stage III Ovarian Epithelial Cancer; Stage IV Breast Cancer; Stage IV Ovarian Epithelial Cancer

  9. Determinants of skin sympathetic nerve responses to isometric exercise.

    PubMed

    Wilson, Thad E; Dyckman, Damian J; Ray, Chester A

    2006-03-01

    Exercise-induced increases in skin sympathetic nerve activity (SSNA) are similar between isometric handgrip (IHG) and leg extension (IKE) performed at 30% of maximal voluntary contraction (MVC). However, the precise effect of exercise intensity and level of fatigue on this relationship is unclear. This study tested the following hypotheses: 1) exercise intensity and fatigue level would not affect the magnitude of exercise-induced increase in SSNA between IHG and IKE, and 2) altering IHG muscle mass would also not affect the magnitude of exercise-induced increase in SSNA. In protocol 1, SSNA (peroneal microneurography) was measured during baseline and during the initial and last 30 s of isometric exercise to volitional fatigue in 12 subjects who randomly performed IHG and IKE bouts at 15, 30, and 45% MVC. In protocol 2, SSNA was measured in eight subjects who performed one-arm IHG at 30% MVC with the addition of IHG of the contralateral arm in 10-s intervals for 1 min. Exercise intensity significantly increased SSNA responses during the first 30 s of IHG (34+/-13, 70+/-11, and 92+/-13% change from baseline) and IKE (30+/-17, 69+/-12, and 76+/-13% change from baseline) for 15, 30, and 45% MVC. During the last 30 s of exercise to volitional fatigue, there were no significant differences in SSNA between exercise intensities or limb. SSNA did not significantly change between one-arm and two-arm IHG. Combined, these data indicate that exercise-induced increases in SSNA are intensity dependent in the initial portion of isometric exercise, but these differences are eliminated with the development of fatigue. Moreover, the magnitude of exercise-induced increase in SSNA responses is not dependent on either muscle mass involved or exercising limb.

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

    PubMed Central

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

    1991-01-01

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

  11. MiR-490-3p sensitizes ovarian cancer cells to cisplatin by directly targeting ABCC2

    PubMed Central

    Tian, Jing; Xu, Yan-Ying; Li, Lian; Hao, Quan

    2017-01-01

    Cisplatin (CDDP) resistance becomes a large obstacle of the beneficial therapy for patients with ovarian cancer. MicroRNAs (miRNAs) act as post-transcriptional regulators of multiple genes’ expression and have been reported to be involved in multi-drug resistance. The purpose of this study was to determine the roles and molecular mechanism of miR-490-3p in the CDDP resistance in ovarian cancer. We found that miR-490-3p was downregulated in CDDP-resistant OVCAR3/CDDP and SKOV3/CDDP cells, which was due to the hypermethylation of miR-490-3p promoter. Functional studies demonstrated that miR-490-3p increased the cell response to CDDP in OVCAR3, SKOV3 and CDDP-resistant cells, while miR-490-3p inhibition resulted in opposite effects. Luciferase assay, real-time PCR and Western blot as well as immunohistochemistry validated that ABCC2 was a direct target of miR-490-3p and miR-490-3p downregulated ABCC2 expression via binding to its 3’UTR. Importantly, silencing of ABCC2 alleviated CDDP resistance induced by miR-490-3p inhibition, while ABCC2 overexpression restored CDDP resistance inhibited by miR-490-3p. In vivo study showed that miR-490-3p enhanced the cytotoxicity of CDDP. Finally, we found that miR-490-3p was downregulated in CDDP-resistant ovarian cancer tissues, while ABCC2 was upregulated. In conclusion, our data indicate that miR-490-3p enhances CDDP sensitivity of ovarian cancer cells through downregulating ABCC2 expression, and suggest that delivery of miR-490-3p might be a potential therapeutic strategy for patients with CDP-resistant ovarian cancer. PMID:28386339

  12. Androstenedione acts on the coeliac ganglion and modulates luteal function via the superior ovarian nerve in the postpartum rat.

    PubMed

    Vallcaneras, Sandra S; Casais, Marilina; Anzulovich, Ana C; Delgado, Silvia M; Sosa, Zulema; Telleria, Carlos M; Rastrilla, Ana M

    2011-07-01

    Androstenedione can affect luteal function via a neural pathway in the late pregnant rat. Here, we investigate whether androstenedione is capable of opposing to regression of pregnancy corpus luteum that occurs after parturition, indirectly, from the coeliac ganglion. Thus, androstenedione was added into the ganglionar compartment of an ex vivo coeliac ganglion-superior ovarian nerve-ovary system isolated from non-lactating rats on day 4 postpartum. At the end of incubation, we measured the abundance of progesterone, androstenedione and oestradiol released into the ovarian compartment. Luteal mRNA expression and activity of progesterone synthesis and degradation enzymes, 3β-hydroxysteroid-dehydrogenase (3β-HSD) and 20α-hydroxysteroid-dehydrogenase (20α-HSD), respectively, as well as the aromatase, Bcl-2, Bax, Fas and FasL transcript levels, were also determined. Additionally, we measured the ovarian release of norepinephrine, nitric oxide and luteal inducible nitric oxide synthase (iNOS) mRNA expression. The presence of androstenedione in the ganglion compartment significantly increased the release of ovarian progesterone, androstenedione and oestradiol without modifying 3β-HSD and 20α-HSD activities or mRNA expression. The ovarian release of oestradiol in response to the presence of androstenedione in the ganglion compartment declined with time of incubation in accord with a reduction in the aromatase mRNA expression. Androstenedione added to the ganglion compartment decreased FasL mRNA expression, without affecting luteal Bcl-2, Bax and Fas transcript levels; also increased the release of norepinephrine, decreased the release of nitric oxide and increased iNOS mRNA. In summary, on day 4 after parturition, androstenedione can mediate a luteotropic effect acting at the coeliac ganglion and transmitting to the ovary a signaling via a neural pathway in association with increased release of norepinephrine, decreased nitric oxide release, and decreased expression

  13. Paclitaxel-resistant human ovarian cancer cells undergo c-Jun NH2-terminal kinase-mediated apoptosis in response to noscapine.

    PubMed

    Zhou, Jun; Gupta, Kamlesh; Yao, Joyce; Ye, Keqiang; Panda, Dulal; Giannakakou, Paraskevi; Joshi, Harish C

    2002-10-18

    We have previously discovered the opium alkaloid noscapine as a microtubule interacting agent that binds to tubulin, alters the dynamics of microtubule assembly, and arrests mammalian cells at mitosis (Ye, K., Ke, Y., Keshava, N., Shanks, J., Kapp, J. A., Tekmal, R. R., Petros, J., and Joshi, H. C. (1998) Proc. Natl. Acad. Sci. U. S. A. 95, 1601-1606; Ye, K., Zhou, J., Landen, J. W., Bradbury, E. M., and Joshi, H. C. (2001) J. Biol. Chem. 276, 46697-46700; Zhou, J., Panda, D., Landen, J. W., Wilson, L., and Joshi, H. C. (2002) J. Biol. Chem. 277, 17200-17208). Here we show that noscapine does not compete with paclitaxel for tubulin binding and can efficiently inhibit the proliferation of both paclitaxel-sensitive and paclitaxel-resistant human ovarian carcinoma cells (i.e. the parental cell line 1A9 and two derivative cell lines, 1A9PTX10 and 1A9PTX22, which harbor beta-tubulin mutations that impair paclitaxel-tubulin interaction (Giannakakou, P., Sackett, D. L., Kang, Y. K., Zhan, Z., Buters, J. T., Fojo, T., and Poruchynsky, M. S. (1997) J. Biol. Chem. 272, 17118-17125). Strikingly, these cells undergo apoptotic death upon noscapine treatment, accompanied by activation of the c-Jun NH(2)-terminal kinases (JNK). Furthermore, inhibition of JNK activity by treatment with antisense oligonucleotide or transfection with dominant-negative JNK blocks noscapine-induced apoptosis. These findings thus indicate a great potential for noscapine in the treatment of paclitaxel-resistant human cancers. In addition, our results suggest that the JNK pathway plays an essential role in microtubule inhibitor-induced apoptosis.

  14. Ovarian and hormonal responses to single or continuous peripheral administration of senktide, a neurokinin 3 receptor agonist, during the follicular phase in goats.

    PubMed

    Endo, N; Rahayu, L P; Ito, Y; Tanaka, T

    2015-10-01

    The present study aimed to investigate the effects of single or continuous administration of a neurokinin 3 receptor agonist, senktide, on hormonal and follicular dynamics in follicular phase goats. Goats were injected with PGF2α in the luteal phase and treated with an intravaginal progesterone device for 10 d. At 12 h after the cessation of progesterone treatment, the goats received a single intravenous injection of senktide (200 nmol, n = 4) or vehicle (n = 4), or continuous intravenous infusion of senktide (20 nmol/min, n = 6) or vehicle (n = 6) for 6 h. Blood sampling and ovarian ultrasonography were performed during the experiment. A single injection of senktide did not influence the number of luteinizing hormone (LH) pulses and mean LH concentration. On the other hand, continuous injection of senktide caused a sustained increase in LH secretion, and mean LH concentration in samples collected at 10-min intervals for 6 h after the start of infusion was higher than that of vehicle-treated goats (2.8 ± 1.3 vs 1.0 ± 0.6 ng/mL, P < 0.01). In 4 of 6 goats, LH concentrations reached their peaks during the 6-h senktide infusion, and ovulation was observed at 48 h after the start of infusion without estrous behavior. The remaining 2 senktide-treated goats and all vehicle-treated goats showed estrus and ovulated at 72 or 96 h after treatment. These results suggest that continuous infusion of senktide in follicular phase goats can cause a sustained increase in LH and advance the time of ovulation.

  15. Kinase insert domain receptor/vascular endothelial growth factor receptor 2 (KDR) genetic variation is associated with ovarian hyperstimulation syndrome

    PubMed Central

    2014-01-01

    Background The objective of this investigation was to determine if kinase insert domain/vascular endothelial growth factor receptor 2 (KDR/VEGFR2) genetic variation was associated with the development of ovarian hyperstimulation syndrome (OHSS) in patients undergoing controlled ovarian hyperstimulation (COH). Methods This was a case–control study of 174 patients who underwent controlled ovarian stimulation. Patient blood samples were genotyped for single nucleotide polymorphisms (SNPs) spanning the KDR locus. OHSS development, clinical outcome variables, SNP and haplotype frequencies were compared between control (n = 155) and OHSS (n = 19) groups. Results Patients who developed OHSS had significantly higher response markers (estradiol levels of the day of hCG administration, number of follicles developed, number of eggs retrieved) than control patients. When adjusted for age and self-identified race, the rs2305945 G/T genotype was associated (P = 0.027) with a decreased risk (OR = 0.30; 95% CI = 0.10, 0.93) of developing OHSS using an overdominant model. The rs2305945 G/T variant was also associated with decreased COH response (number of follicles, number of eggs retrieved) in an overdominant model. The rs2305948, rs1870378, rs2305945 (C-T-G) haplotype was associated with both decreased COH response and OHSS risk (unadjusted OR = 0.10; 95% CI = 0.01, 0.80, P = 0.031). Conclusions The KDR receptor is believed to play a central role OHSS development and is a target for pharmacological prevention of OHSS. These results indicate that genetic variation in the KDR gene may impact individual risk of developing OHSS from COH. In addition, the rs2305948 SNP and C-T-G haplotype might serve as potential biomarkers for poor ovarian response to COH. PMID:24886133

  16. [Patient self-determination--reflections on critical and responsible management].

    PubMed

    Eibach, Ulrich

    2003-10-01

    The assumption on which this article is based is that Living Wills represent possible protection against medical and nursing treatments which are detrimental to one's own well-being in the phases of life in which one is no longer or only to a very limited extent capable of making decisions onself. But Living Wills cannot afford protection against grave strokes of fate and safeguard a life of self-determination until death. A Living Will can only constitute a helpful protective function, not only for the sick person but also for all those involved in his/her treatment and care, if it is discussed extensively with others so that these persons can interpret its meaning with respect to medical and nursing treatment in the sense intended by the patient. The article provides indications as to how Living Wills and their handling can best make this protective function possible.

  17. Subtypes of Ovarian Cancer and Ovarian Cancer Screening

    PubMed Central

    Koshiyama, Masafumi; Matsumura, Noriomi; Konishi, Ikuo

    2017-01-01

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

  18. The Immune System in the Pathogenesis of Ovarian Cancer

    PubMed Central

    Charbonneau, Bridget; Goode, Ellen L.; Kalli, Kimberly R.; Knutson, Keith L.; DeRycke, Melissa S.

    2014-01-01

    Clinical outcomes in ovarian cancer are heterogeneous even when considering common features such as stage, response to therapy, and grade. This disparity in outcomes warrants further exploration into tumor and host characteristics. One compelling host characteristic is the immune response to ovarian cancer. While several studies have confirmed a prominent role for the immune system in modifying the clinical course of the disease, recent genetic and protein analyses also suggest a role in disease incidence. Recent studies also show that anti-tumor immunity is often negated by immune suppressive cells present in the tumor microenvironment. These suppressive immune cells also directly enhance the pathogenesis through the release of various cytokines and chemokines, which together form an integrated pathologic network. Thus, future research into immunotherapy targeting ovarian cancer will likely become increasingly focused on combination approaches that simultaneously augment immunity while preventing local immune suppression or by disrupting critical cytokine networks. PMID:23582060

  19. Long-Lived Neighbors Determine the Rheological Response of Glasses

    NASA Astrophysics Data System (ADS)

    Laurati, M.; Maßhoff, P.; Mutch, K. J.; Egelhaaf, S. U.; Zaccone, A.

    2017-01-01

    Glasses exhibit a liquidlike structure but a solidlike rheological response with plastic deformations only occurring beyond yielding. Thus, predicting the rheological behavior from the microscopic structure is difficult, but important for materials science. Here, we consider colloidal suspensions and propose to supplement the static structural information with the local dynamics, namely, the rearrangement and breaking of the cage of neighbors. This is quantified by the mean squared nonaffine displacement and the number of particles that remain nearest neighbors for a long time, i.e., long-lived neighbors, respectively. Both quantities are followed under shear using confocal microscopy and are the basis to calculate the affine and nonaffine contributions to the elastic stress, which is complemented by the viscoelastic stress to give the total stress. During start-up of shear, the model predicts three transient regimes that result from the interplay of affine, nonaffine, and viscoelastic contributions. Our prediction quantitatively agrees with rheological data and their dependencies on volume fraction and shear rate.

  20. Targeted therapy for epithelial ovarian cancer.

    PubMed

    Sharma, Sameer; Odunsi, Kunle

    2005-06-01

    Ovarian cancer is the leading cause of death in women with gynecological malignancies and overall survival for patients with advanced epithelial ovarian cancer (EOC) remains poor. The majority of patients recur after initial treatment. A strategy for improving outcome is to minimise recurrence via targeted therapy in patients after front-line therapy, or more appropriately as consolidation therapy. EOC represents an attractive target because of the biology of the disease and that the bulk of disease occurs in the peritoneal cavity. To initiate targeted therapy, a candidate target must be identified. Innovative approaches via targeted therapy to control metastatic residual EOC are currently under investigation. The targets are molecules and pathways, on which cancer cells depend to proliferate, invade, metastasise and prevent apoptosis. Potential targeted therapies include: proapoptototic therapy, suicide gene therapy, signal transduction, antiangiogenesis, immunotherapy and cytokine therapy. The utilisation of these targets in the clinic demands carefully conducted, well-coordinated but discovery-oriented translational research in the form of clinical trials that can quickly assess alternative strategies or combination of strategies that could result in clinical benefit. Therefore, targeted therapy for epithelial ovarian cancer, especially after complete response to standard regimens, represents a paradigm whose time has come to be nurtured.

  1. Proteomic analysis of chinook salmon (Oncorhynchus tshawytscha) ovarian fluid.

    PubMed

    Johnson, Sheri L; Villarroel, Marsha; Rosengrave, Patrice; Carne, Alan; Kleffmann, Torsten; Lokman, P Mark; Gemmell, Neil J

    2014-01-01

    The ovarian, or coelomic, fluid that is released with the egg mass of many fishes is increasingly found to play an important role in several biological processes crucial for reproductive success. These include maintenance of oocyte fertility and developmental competence, prolonging of sperm motility, and enhancing sperm swimming speed. Here we examined if and how the proteome of chinook salmon (Oncorhynchus tshawytscha) ovarian fluid varied among females and then sought to examine the composition of this fluid. Ovarian fluid in chinook salmon was analyzed using 1D SDS PAGE and LC-MS/MS tryptic digest screened against Mascot and Sequest databases. We found marked differences in the number and concentrations of proteins in salmon ovarian fluid across different females. A total of 174 proteins were identified in ovarian fluid, 47 of which were represented by six or more peptides, belonging to one of six Gene Ontology pathways. The response to chemical stimulus and response to hypoxia pathways were best represented, accounting for 26 of the 174 proteins. The current data set provides a resource that furthers our understanding of those factors that influence successful egg production and fertilisation in salmonids and other species.

  2. Proteomic Analysis of Chinook Salmon (Oncorhynchus tshawytscha) Ovarian Fluid

    PubMed Central

    Johnson, Sheri L.; Villarroel, Marsha; Rosengrave, Patrice; Carne, Alan; Kleffmann, Torsten; Lokman, P. Mark; Gemmell, Neil J.

    2014-01-01

    The ovarian, or coelomic, fluid that is released with the egg mass of many fishes is increasingly found to play an important role in several biological processes crucial for reproductive success. These include maintenance of oocyte fertility and developmental competence, prolonging of sperm motility, and enhancing sperm swimming speed. Here we examined if and how the proteome of chinook salmon (Oncorhynchus tshawytscha) ovarian fluid varied among females and then sought to examine the composition of this fluid. Ovarian fluid in chinook salmon was analyzed using 1D SDS PAGE and LC-MS/MS tryptic digest screened against Mascot and Sequest databases. We found marked differences in the number and concentrations of proteins in salmon ovarian fluid across different females. A total of 174 proteins were identified in ovarian fluid, 47 of which were represented by six or more peptides, belonging to one of six Gene Ontology pathways. The response to chemical stimulus and response to hypoxia pathways were best represented, accounting for 26 of the 174 proteins. The current data set provides a resource that furthers our understanding of those factors that influence successful egg production and fertilisation in salmonids and other species. PMID:25089903

  3. Three determinants in ezrin are responsible for cell extension activity.

    PubMed Central

    Martin, M; Roy, C; Montcourrier, P; Sahuquet, A; Mangeat, P

    1997-01-01

    The ERM proteins--ezrin, radixin, and moesin--are key players in membrane-cytoskeleton interactions. In insect cells infected with recombinant baculoviruses, amino acids 1-115 of ezrin were shown to inhibit an actin- and tubulin-dependent cell-extension activity located in ezrin C-terminal domain (ezrin310-586), whereas full-length ezrin1-586 did not induce any morphological change. To refine the mapping of functional domains of ezrin, 30 additional constructs were overexpressed in Sf9 cells, and the resulting effect of each was qualitatively and semiquantitatively compared. The removal of amino acids 13-30 was sufficient to release a cell-extension phenotype. This effect was abrogated if the 21 distal-most C-terminal amino acids were subsequently deleted (ezrin31-565), confirming the existence of a head-to-tail regulation in the whole molecule. Surprisingly, the deletion in full-length ezrin of the same 21 amino acids provided strong cell-extension competence to ezrin1-565, and this property was recovered in N-terminal constructs as short as ezrin1-310. Within ezrin1-310, amino acid sequences 13-30 and 281-310 were important determinants and acted in cooperation to induce cytoskeleton mobilization. In addition, these same residues are part of a new actin-binding site characterized in vitro in ezrin N-terminal domain. Images PMID:9285824

  4. A Novel Approach to Identify Genes that Modulate Response of Human Ovarian Cancer Cells to Chemotherapeutic Agents Using High-Throughput RNA Interference

    DTIC Science & Technology

    2008-12-01

    sensitizing targets of cisplatin and paclitaxel in SKOV-3 cells. • Performed a kinase siRNA library screening for modulators of cisplatin response...Performed a kinase siRNA library screening for modulators of paclitaxel response. • Identified kinase genes whose silencing enhanced the response

  5. Fluvial response to subsidence determined from remote sensing

    SciTech Connect

    Kraus, M.J. )

    1990-05-01

    Well-exposed rocks of the fluvial Willwood Formation covering approximately 5,000 km{sup 2} of the central part of the Big Horn basin, Wyoming, were analyzed with Thematic Mapper (TM) data. False-color images and field analysis were used to characterize and map large-scale lithologic packages in this lower Eocene unit. Field criteria used to distinguish among the packages include mudstone coloration and type and abundance of nodules, both of which reflect the type of alluvial paleosol that developed; abundance, geometry, and paleotransport direction of sand bodies; and abundance and geometry of carbonaceous shales. The lithologic packages reflect both spatial and temporal variability; biostratigraphic data were used to establish which packages are time correlative. Differences among time-correlative fluvial packages (facies) reflect variability in local moisture regimes and sediment accumulation rates, factors that influenced the location of major stream channels and the types of palesols that formed on overbank deposits. Facies distribution demonstrates that east-west-trending lineaments, which segment the Bighorn Mountains, extend into the basin and were active faults during the early Eocene. The lithologic heterogeneity is attributed to differential crustal subsidence on either side of the lineament. Vertical changes in lithology record temporal variability in basin subsidence rates. Subsidence rates slowed over time producing brighter mudstones (more mature paleosols) higher in the section and changes in carbonaceous shale type and abundance. The location of major channel sand bodies also appears to have shifted westward over time. Fluvial Willwood rocks arc capped by the lacustrine Tatman Formation in certain parts of the basin. TM images suggest that the north-south extent of the lake deposits was determined by the location of several of the lineaments.

  6. Ovarian reserve screening before contraception?

    PubMed

    Kushnir, Vitaly A; Barad, David H; Gleicher, Norbert

    2014-11-01

    Women are increasingly delaying conception to later years. Hormonal contraception induces artificial cyclicity, which does not, like natural cyclicity, reflect normal, physiological ovarian behaviour. Therefore, long-term users of hormonal contraceptives, in particular, fail to derive potential diagnostic benefits from changes in menstrual cyclicity, which usually alerts patients and physicians to developing ovarian pathology. Timely diagnosis of ovarian problems is further hampered, as anti-Müllerian hormone is suppressed by hormonal contraceptives, making the accurate assessment of functional ovarian reserve more difficult. Women on long-term hormonal contraceptives who develop premature ovarian senescence at young ages, therefore, often go undiagnosed until termination of hormonal contraception, when they present with either post-contraception amenorrhea, other menstrual abnormalities or infertility. As evolving screening options now permit the detection of young women at risk for premature ovarian senescence, it is proposed that young women are offered 'risk screening' for premature ovarian senescence before starting long-term hormonal contraception. A potential protocol is outlined.

  7. Chromosome abnormalities in primary ovarian cancer

    SciTech Connect

    Yonescu, R.; Currie, J.; Griffin, C.A.

    1994-09-01

    Chromosome abnormalities that are specific and recurrent may occur in regions of the genome that are involved in the conversion of normal cells to those with tumorigenic potential. Ovarian cancer is the primary cause of death among patients with gynecological malignancies. We have performed cytogenetic analysis of 16 ovarian tumors from women age 28-82. Three tumors of low malignant potential and three granulosa cell tumors had normal karyotypes. To look for the presence of trisomy 12, which has been suggested to be a common aberration in this group of tumors, interphase fluorescence in situ hybridization was performed on direct preparations from three of these tumors using a probe for alpha satellite sequences of chromosome 12. In the 3 preparations, 92-98 percent of the cells contained two copies of chromosome 12, indicating that trisomy 12 is not a universal finding in low grade ovarian tumors. Endometrioid carcinoma of the ovary is histologically indistinguishable from endometial carcinoma of the uterus. We studied 10 endometrioid tumors to determine the degree of genetic similarity between these two carcinomas. Six out of ten endometrioid tumors showed a near-triploid modal number, and one presented with a tetraploid modal number. Eight of the ten contained structural chromosome abnormalities, of which the most frequent were 1p- (5 tumors), 19q+ (3 tumors), 6q- or ins(6) (4 tumors), 3q- or 3q+ (4 tumors). These cytogenetic results resemble those reported for papillary ovarian tumors and differ from those of endometrial carcinoma of the uterus. We conclude that despite the histologic similarities between the endometrioid and endometrial carcinomas, the genetic abnormalities in the genesis of these tumors differ significantly.

  8. Suitability of rapid energy magnitude determinations for emergency response purposes

    NASA Astrophysics Data System (ADS)

    Di Giacomo, Domenico; Parolai, Stefano; Bormann, Peter; Grosser, Helmut; Saul, Joachim; Wang, Rongjiang; Zschau, Jochen

    2010-01-01

    It is common practice in the seismological community to use, especially for large earthquakes, the moment magnitude Mw as a unique magnitude parameter to evaluate the earthquake's damage potential. However, as a static measure of earthquake size, Mw does not provide direct information about the released seismic wave energy and its high frequency content, which is the more interesting information both for engineering purposes and for a rapid assessment of the earthquake's shaking potential. Therefore, we recommend to provide to disaster management organizations besides Mw also sufficiently accurate energy magnitude determinations as soon as possible after large earthquakes. We developed and extensively tested a rapid method for calculating the energy magnitude Me within about 10-15 min after an earthquake's occurrence. The method is based on pre-calculated spectral amplitude decay functions obtained from numerical simulations of Green's functions. After empirical validation, the procedure has been applied offline to a large data set of 767 shallow earthquakes that have been grouped according to their type of mechanism (strike-slip, normal faulting, thrust faulting, etc.). The suitability of the proposed approach is discussed by comparing our rapid Me estimates with Mw published by GCMT as well as with Mw and Me reported by the USGS. Mw is on average slightly larger than our Me for all types of mechanisms. No clear dependence on source mechanism is observed for our Me estimates. In contrast, Me from the USGS is generally larger than Mw for strike-slip earthquakes and generally smaller for the other source types. For ~67 per cent of the event data set our Me differs <= +/-0.3 magnitude units (m.u.) from the respective Me values published by the USGS. However, larger discrepancies (up to 0.8 m.u.) may occur for strike-slip events. A reason of that may be the overcorrection of the energy flux applied by the USGS for this type of earthquakes. We follow the original

  9. Cytokines and Prognostic Factors in Epithelial Ovarian Cancer

    PubMed Central

    Jammal, Millena Prata; Martins-Filho, Agrimaldo; Silveira, Thales Parenti; Murta, Eddie Fernando Candido; Nomelini, Rosekeila Simões

    2016-01-01

    INTRODUCTION Ovarian cancer has a high mortality and delayed diagnosis. Inflammation is a risk factor for ovarian cancer, and the inflammatory response is involved in almost all stages of tumor development. Immunohistochemical staining in stroma and epithelium of a panel of cytokines in benign and malignant ovarian neoplasm was evaluated. In addition, immunostaining was related to prognostic factors in malignant tumors. METHOD The study group comprised 28 ovarian benign neoplasias and 28 ovarian malignant neoplasms. A panel of cytokines was evaluated by immunohistochemistry (Th1: IL-2 and IL-8; Th2: IL-5, IL-6, and IL-10; and TNFR1). Chi-square test with Yates’ correction was used, which was considered significant if less than 0.05. RESULTS TNFR1, IL-5, and IL-10 had more frequent immunostaining 2/3 in benign neoplasms compared with malignant tumors. Malignant tumors had more frequent immunostaining 2/3 for IL-2 in relation to benign tumors. The immunostaining 0/1 of IL 8 was more frequent in the stroma of benign neoplasms compared with malignant neoplasms. Evaluation of the ovarian cancer stroma showed that histological grade 3 was significantly correlated with staining 2/3 for IL-2 (P = 0.004). Women whose disease-free survival was less than 2.5 years had TNFR1 stromal staining 2/3 (P = 0.03) more frequently. CONCLUSION IL-2 and TNFR1 stromal immunostaining are related prognostic factors in ovarian cancer and can be the target of new therapeutic strategies. PMID:27512342

  10. Primary ovarian insufficiency: an update

    PubMed Central

    Cox, Leticia; Liu, James H

    2014-01-01

    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. PMID:24591848

  11. [Ovarian fibrothecal tumor: case report].

    PubMed

    González Gleason, Alejandro; De la Cruz, Sebastián Iris; Torres Salas, María Esther; Guzmán Patraca, Carlos; Chavarría Olarte, María Eugenia; Reyes Fuentes, Alejandro

    2002-05-01

    Tumors with stromal or sex-cords origin are scarce, and comprise only 5% or less of all ovarian tumors. Nevertheless functional tumor types are the most striking ones, only few of them produce hormonal symptoms. Fibrothecal tumors belong to the stromal cells tumor class, with differentiation towards both fibroblastic-type cells of thecal cell. We present a case report of a 68 years old woman with an ovarian tumor sized 14 x 9 x 7 cm. The treatment was the extirpation of the tumor. Microscopic evaluation of the surgical piece reported an ovarian fibrothecal tumor.

  12. What Are the Key Statistics about Ovarian Cancer?

    MedlinePlus

    ... Cancer About Ovarian Cancer What Are the Key Statistics About Ovarian Cancer? The American Cancer Society estimates ... ovarian cancer is about 1 in 100. (These statistics don’t count low malignant potential ovarian tumors.) ...

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

    MedlinePlus

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

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

    PubMed Central

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

    2005-01-01

    Ovarian cancer represents the fifth leading cause of death from all cancers for women. During the last decades overall survival has improved due to the use of new chemotherapy schedules. Still, the majority of patients die of this disease. Research reveals that ovarian cancer patients exhibit significant immune responses against their tumor. In this review the knowledge obtained thus far on the interaction of ovarian cancer tumor cells and the immune system is discussed. Furthermore the role of p53 as tumor antigen and its potential role as target antigen in ovarian cancer is summarized. Based on the increased knowledge on the role of the immune system in ovarian cancer major improvements are to be expected of immunotherapy based treatment of this disease. PMID:16164749

  15. Toll-like receptor 8: augmentation of innate immunity in platinum resistant ovarian carcinoma

    PubMed Central

    Brueseke, Taylor J; Tewari, Krishnansu S

    2013-01-01

    Ovarian cancer is the most deadly gynecologic cancer, with 15,000 anticipated deaths within the United States alone in 2012, and new treatment strategies are needed. Ovarian cancer tumors are known to host an immunosuppressive microenvironment. This suppression may be reversible via activation of the innate immune response. Toll-like receptor 8 activates innate immunity while simultaneously inhibiting the effects of regulatory T cells within the ovarian cancer tumors. VTX-2337 is a novel small molecule ligand of Toll-like receptor 8 and is currently the subject of a Phase II randomized, double-blind, placebo-controlled trial Gynecologic Oncology Group (GOG)-3003 for patients with recurrent platinum-resistant ovarian cancer. We look forward to the results of this trial as support for the paradigm of process therapy in the treatment of ovarian cancer. PMID:23723721

  16. Role of benign ovarian cysts in the development of adenomyosis

    PubMed Central

    Alam, Sadaf; Ahmad, Sajjad; Khan, Muhammad M.; Nasir, Sabeen; Sharif, Naveed; Ziaullah, Sara; Khalid, Ahmareen; Rauf, Fozia

    2016-01-01

    Objectives: To assess the association of adenomyotic foci with co-existing benign ovarian cysts. Methods: This prospective cross-sectional study consisted of 100 consecutive hysterectomy specimens referred to Histopathology Section of Pathology Department, Peshawar Medical College, Peshawar, Pakistan by its attached teaching hospitals from January 2011 to December 2012. Hematoxylin and eosin stained sections were examined for adenomyotic foci and the presence of co-existent ovarian cysts. For evaluation of estrogen receptor (ER) status immunohistochemical stains were applied and H-scoring system was used with a score >50 as positive. Results: Out of the 100 hysterectomy specimens, 25 cases had both adenomyosis and ovarian cysts. The ER status of adenomyotic foci was positive in 20% cases and negative in 80% cases. The commonest type of ovarian cyst was hemorrhagic luteal cyst (28%), followed by serous and mucinous cystadenoma (20%) each. Out of the 28% cases of functional cysts, 71.5% were ER positive and 28.5% were ER negative. The p-value for association of ER status of adenomyotic foci with functional cysts was 0.0004; however, p-value was not significant in comparing cases with controls. All 72% cases of nonfunctional cysts were ER negative. However, 44% of functional cysts were not associated with adenomyotic foci. Conclusion: This study concludes that besides functional ovarian cysts, other local factors may be responsible for the development of adenomyosis. PMID:27570851

  17. Altered glutamine metabolism in platinum resistant ovarian cancer

    PubMed Central

    Hudson, Chantelle D.; Savadelis, Alyssa; Nagaraj, Anil Belur; Joseph, Peronne; Avril, Stefanie; DiFeo, Analisa; Avril, Norbert

    2016-01-01

    Ovarian cancer is characterized by an increase in cellular energy metabolism, which is predominantly satisfied by glucose and glutamine. Targeting metabolic pathways is an attractive approach to enhance the therapeutic effectiveness and to potentially overcome drug resistance in ovarian cancer. In platinum-sensitive ovarian cancer cell lines the metabolism of both, glucose and glutamine was initially up-regulated in response to platinum treatment. In contrast, platinum-resistant cells revealed a significant dependency on the presence of glutamine, with an upregulated expression of glutamine transporter ASCT2 and glutaminase. This resulted in a higher oxygen consumption rate compared to platinum-sensitive cell lines reflecting the increased dependency of glutamine utilization through the tricarboxylic acid cycle. The important role of glutamine metabolism was confirmed by stable overexpression of glutaminase, which conferred platinum resistance. Conversely, shRNA knockdown of glutaminase in platinum resistant cells resulted in re-sensitization to platinum treatment. Importantly, combining the glutaminase inhibitor BPTES with platinum synergistically inhibited platinum sensitive and resistant ovarian cancers in vitro. Apoptotic induction was significantly increased using platinum together with BPTES compared to either treatment alone. Our findings suggest that targeting glutamine metabolism together with platinum based chemotherapy offers a potential treatment strategy particularly in drug resistant ovarian cancer. PMID:27191653

  18. [Polycystic ovary syndrome of extra-ovarian origin. Review].

    PubMed

    Terán Dávila, J; Teppa-Garrán, A D

    2001-03-01

    An established fact in the polycystic ovarian syndrome (POS) is an abnormal ovarian steroidogenesis. Though this suggest an intrinsic ovarian defect, the syndrome could also be influenced by factors outside the ovaries. Although of unknown etiology, the POS is one of the most frequent endocrine disorders in the gynecologic practice. The disorder is characterized by ultrasound findings of enlarged polycystic ovaries, hyperandrogenism, menstrual disorders, obesity and including the appearance of infertility. There are a series of mechanisms involved in the extraovarian androgen increase in patients with POS. Among these mechanisms are implicated those of central and peripheral origin, genetic factors and adrenocortical dysfunction. In the same way, the alterations produced could imply genetic, molecular biological, biochemical, physiological and endocrinological factors. Sometimes all these factors could interact at the same time. The high serum androgen level could stop the pituitary gonadotropin production, either as a direct mechanism or as a result of its peripheral conversion. The increased androgens also explain the manifestations of clinical acne, hirsutism, and the detention in follicular ovarian maturation. All these manifestations are related with the menstrual disorders, anovulation, and infertility that these patients develop. The characteristics of the extraovarian POS include the 17-hydroxyprogesterone elevation in response to the ACTH test and the dexamethasone suppression of adrenal androgens. It is possible to improve the ovarian function in some patients with POS. This could be achieved with clomiphene citrate associated with glucocorticoids to induce ovulation.

  19. Pegylated Liposomal Doxorubicin Hydrochloride, Carboplatin, Veliparib, and Bevacizumab in Treating Patients With Recurrent Ovarian Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer

    ClinicalTrials.gov

    2017-01-31

    Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Cystadenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Ovarian Carcinoma

  20. Excessive Ovarian Production of Nerve Growth Factor Facilitates Development of Cystic Ovarian Morphology in Mice and Is a Feature of Polycystic Ovarian Syndrome in Humans

    PubMed Central

    Dissen, Gregory A.; Garcia-Rudaz, Cecilia; Paredes, Alfonso; Mayer, Christine; Mayerhofer, Artur; Ojeda, Sergio R.

    2009-01-01

    Although ovarian nerve growth factor (NGF) facilitates follicular development and ovulation, an excess of the neurotrophin in the rodent ovary reduces ovulatory capacity and causes development of precystic follicles. Here we show that ovarian NGF production is enhanced in patients with polycystic ovarian syndrome (PCOS) and that transgenically driven overproduction of NGF targeted to the ovary results in cystic morphology, when accompanied by elevated LH levels. NGF levels are increased in the follicular fluid from PCOS ovaries and in the culture medium of granulosa cells from PCOS patients, as compared with non-PCOS patients. Ovaries from transgenic mice carrying the NGF gene targeted to thecal-interstitial cells by the 17α-hydroxylase gene promoter produce more NGF than wild-type (WT) ovaries and are hyperinnervated by sympathetic nerves. Antral follicle growth is arrested resulting in accumulation of intermediate size follicles, many of which are apoptotic. Peripubertal transgenic mice respond to a gonadotropin challenge with a greater increase in plasma 17-hydroxyprogesterone, estradiol, and testosterone levels than WT controls. Transgenic mice also exhibit a reduced ovulatory response, delayed puberty, and reduced fertility, as assessed by a prolonged interval between litters, and a reduced number of pups per litter. Sustained, but mild, elevation of plasma LH levels results in a heightened incidence of ovarian follicular cysts in transgenic mice as compared with WT controls. These results suggest that overproduction of ovarian NGF is a component of polycystic ovarian morphology in both humans and rodents and that a persistent elevation in plasma LH levels is required for the morphological abnormalities to appear. PMID:19264868

  1. Excessive ovarian production of nerve growth factor facilitates development of cystic ovarian morphology in mice and is a feature of polycystic ovarian syndrome in humans.

    PubMed

    Dissen, Gregory A; Garcia-Rudaz, Cecilia; Paredes, Alfonso; Mayer, Christine; Mayerhofer, Artur; Ojeda, Sergio R

    2009-06-01

    Although ovarian nerve growth factor (NGF) facilitates follicular development and ovulation, an excess of the neurotrophin in the rodent ovary reduces ovulatory capacity and causes development of precystic follicles. Here we show that ovarian NGF production is enhanced in patients with polycystic ovarian syndrome (PCOS) and that transgenically driven overproduction of NGF targeted to the ovary results in cystic morphology, when accompanied by elevated LH levels. NGF levels are increased in the follicular fluid from PCOS ovaries and in the culture medium of granulosa cells from PCOS patients, as compared with non-PCOS patients. Ovaries from transgenic mice carrying the NGF gene targeted to thecal-interstitial cells by the 17alpha-hydroxylase gene promoter produce more NGF than wild-type (WT) ovaries and are hyperinnervated by sympathetic nerves. Antral follicle growth is arrested resulting in accumulation of intermediate size follicles, many of which are apoptotic. Peripubertal transgenic mice respond to a gonadotropin challenge with a greater increase in plasma 17-hydroxyprogesterone, estradiol, and testosterone levels than WT controls. Transgenic mice also exhibit a reduced ovulatory response, delayed puberty, and reduced fertility, as assessed by a prolonged interval between litters, and a reduced number of pups per litter. Sustained, but mild, elevation of plasma LH levels results in a heightened incidence of ovarian follicular cysts in transgenic mice as compared with WT controls. These results suggest that overproduction of ovarian NGF is a component of polycystic ovarian morphology in both humans and rodents and that a persistent elevation in plasma LH levels is required for the morphological abnormalities to appear.

  2. The heterogeneity of ovarian cancer.

    PubMed

    Meinhold-Heerlein, I; Hauptmann, S

    2014-02-01

    Ovarian cancer carries the worst prognosis of all gynecological malignancies. This is mainly due to its resistance against commonly used cytostatic drugs as well as the lack of a screening method for its detection at an early stage. Both basic and translational research have shown over the past decades that ovarian cancer as a medical term includes several types of tumors with different phenotypes, molecular biology, etiology, tumor progression, and even different prognosis. In this issue of Archives of Gynecology and Obstetrics, J. Dietel presents a review article about novel findings of the etiopathogenesis of ovarian cancer and the role that fallopian tubes may play. He also outlines the implied clinical consequences. Here, we give a brief overview of the heterogeneity of ovarian cancer to introduce the topic.

  3. [Premature ovarian failure: present aspects].

    PubMed

    Vilodre, Luiz Cesar; Moretto, Marcelo; Kohek, Maria Beatriz da Fonte; Spritzer, Poli Mara

    2007-08-01

    Premature ovarian failure occurs in approximately 1:1000 women before 30 years, 1:250 by 35 years and 1:100 by the age of 40. It is characterized by primary or secondary amenorrhea and cannot be considered as definitive because spontaneous conception may occur in 5 to 10% of cases. In 95% of cases, premature ovarian failure is sporadic. The known causes of premature ovarian failure include chromosomal defects, autoimmune diseases, exposure to radiation or chemotherapy, surgical procedures, and certain drugs. Frequently, however, the etiology is not clear and these cases are considered to be idiopathic. Premature ovarian failure is defined by gonadal failure and high serum follicle-stimulating hormone (FSH) levels. Clinical approach includes emotional support, hormonal therapy with estrogens and progesterone or progestogens, infertility treatment, and prevention of osteoporosis and potential cardiovascular risk.

  4. Molecular Imaging of Ovarian Cancer

    PubMed Central

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

    2016-01-01

    Ovarian cancer is the most lethal gynecologic malignancy and the fifth leading cause of cancer-related death in women. Over the past decade, medical imaging has played an increasingly valuable role in the diagnosis, staging, and treatment planning of the disease. In this “Focus on Molecular Imaging” review, we seek to provide a brief yet informative survey of the current state of the molecular imaging of ovarian cancer. The article is divided into sections according to modality, covering recent advances in the MR, PET, SPECT, ultrasound, and optical imaging of ovarian cancer. Although primary emphasis is given to clinical studies, preclinical investigations that are particularly innovative and promising are discussed as well. Ultimately, we are hopeful that the combination of technologic innovations, novel imaging probes, and further integration of imaging into clinical protocols will lead to significant improvements in the survival rate for ovarian cancer. PMID:27127223

  5. How Is Ovarian Cancer Staged?

    MedlinePlus

    ... recent FIGO staging. Stages of ovarian and fallopian tube cancer Once a patient's T, N, and M ... only within the ovary (or ovaries) or fallopian tube(s). It has not spread to organs and tissues ...

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

    PubMed

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

    2015-01-01

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

  7. Role of epigenomics in ovarian and endometrial cancers.

    PubMed

    Balch, Curtis; Matei, Daniela E; Huang, Tim H-M; Nephew, Kenneth P

    2010-06-01

    Ovarian cancer is the most lethal gynecologic malignancy and while constituting only 3% of all female cancers, it causes 14,600 deaths in the USA annually. Endometrial cancer, the most diagnosed and second-most fatal gynecologic cancer, afflicts over 40,000 US women annually, causing an estimated 7780 deaths in 2009. In both advanced ovarian and endometrial carcinomas, the majority of initially therapy-responsive tumors eventually evolve to a fully drug-resistant phenotype. In addition to genetic mutations, epigenetic anomalies are frequent in both gynecologic malignancies, including aberrant DNA methylation, atypical histone modifications and dysregulated expression of distinct microRNAs, resulting in altered gene-expression patterns favoring cell survival. In this article, we summarize the most recent hypotheses regarding the role of epigenetics in ovarian and endometrial cancers, including a possible role in tumor 'stemness' and also evaluate the possible therapeutic benefits of reversal of these oncogenic chromatin aberrations.

  8. Epigenetic Therapies for Chemoresensitization of Epithelial Ovarian Cancer

    PubMed Central

    Matei, Daniela E.; Nephew, Kenneth P.

    2009-01-01

    Summary Epigenetic drugs have been shown to enhance gene expression and drug sensitivity in ovarian cancer cell lines and animal models. Based on promising pre-clinical studies, DNA methylation inhibitors in combination with existing chemotherapeutic agents have the potential for overcoming acquired drug resistance, laying the foundation for this specific class of epigenetic drug in ovarian cancer clinical trials. The recent completion of phase I trials of decitabine have yielded important information on dosing schedules and biological endpoints for evaluating patient responses. In addition, epigenetic drug effects on pharmacodyamic targets are beginning to emerge, and predictive epigenetic biomarkers and next generation epigenome therapeutics are being developed for application in clinical settings for ovarian cancer patients. PMID:19854495

  9. Prognostic Biomarkers in Ovarian Cancer

    PubMed Central

    Huang, Jie; Hu, Wei; Sood, Anil K

    2014-01-01

    Epithelial ovarian cancer (EOC) remains the most lethal gynecological malignancy despite several decades of progress in diagnosis and treatment. Taking advantage of the robust development of discovery and utility of prognostic biomarkers, clinicians and researchers are developing personalized and targeted treatment strategies. This review encompasses recently discovered biomarkers of ovarian cancer, the utility of published prognostic biomarkers for EOC (especially biomarkers related to angiogenesis and key signaling pathways), and their integration into clinical practice. PMID:22045356

  10. Genetic Modifiers of Ovarian Cancer

    DTIC Science & Technology

    2012-06-01

    association study ( GWAS ) for ovarian cancer in BRCA1 mutation carriers was initiated in an effort to identify common genetic variants that modify... GWAS of 1250 BRCA1 mutation carriers diagnosed with breast cancer and 1250 unaffected BRCA1 carriers using Human660W-Quad arrays. The 1250 unaffected...cancer on H uman660W-Quad arrays. In addition we acquired GWAS genotype data for 120 additional BRCA1 mutation carriers affected with ovarian

  11. The Role of Long Non-Coding RNAs in Ovarian Cancer

    PubMed Central

    Nikpayam, Elahe; Tasharrofi, Behnoosh; Sarrafzadeh, Shaghayegh; Ghafouri-Fard, Soudeh

    2017-01-01

    Ovarian cancer is the most fatal tumor of female’s reproductive system, and several genetics and environmental factors are involved in its development. Various studies have already identified some suitable biomarkers to facilitate the early detection, the prognosis evaluation, and the assessment of treatment response. However, the aim of this review is to investigate the role of long non-coding RNAs (lncRNAs) in tumorigenesis process of ovarian cancer and their potential applications as ovarian cancer biomarkers. We performed an online literature search of the MEDLINE/PubMed databases using the keywords, including ovarian cancer, lncRNA, and biomarker. We found that several lncRNAs have been shown to be deregulated in ovarian cancer and the specific mechanism of their enrollment in ovarian cancer has been defined for a few of them. In addition, expression profiling has revealed an association between lncRNAs and patients’ survival, metastasis potential, as well as treatment response. Expression profiling and methylation analysis of lncRNAs in ovarian cancer may lead to the identification of novel biomarkers that can help in the classification of patients based on prognosis and treatment response. PMID:27664137

  12. Spy1 participates in the proliferation and apoptosis of epithelial ovarian cancer.

    PubMed

    Lu, Shumin; Liu, Rong; Su, Min; Wei, Yingze; Yang, Shuyun; He, Song; Wang, Xia; Qiang, Fulin; Chen, Chen; Zhao, Shuyang; Zhang, Weiwei; Xu, Pan; Mao, Guoxin

    2016-02-01

    This study focused on determining the role of Spy1 in human epithelial ovarian cancer (EOC). Speedy is a novel cell cycle protein capable of promoting cell proliferation. In this study, western blot and immunohistochemistrical analyses were performed to detect the expression of Spy1 in ovarian cancer. Spy1 protein levels increased with ovarian cancer grade, and Kaplan-Meier curve showed that overexpression of Spy1 was significantly correlated with reduced patient survival. In vitro, Spy1 depletion in ovarian cell lines led to reduced proliferation according to CCK8 and plate colony assays. The expression of Spy1 was positively related to pThr187-p27. Flow cytometry revealed that the reduced expression of Spy1 induced the apoptosis of the EOC cells. In summary, our findings suggested that Spy1 may be a novel independent prognostic predictor of survival for ovarian patients.

  13. Role of nerve growth factor and its TRKA receptor in normal ovarian and epithelial ovarian cancer angiogenesis.

    PubMed

    Vera, Carolina; Tapia, Verónica; Vega, Margarita; Romero, Carmen

    2014-08-10

    In normal ovarian function a controlled angiogenesis is essential. Several growth factors are involved in this process, such as the vascular endothelial growth factor (VEGF) and nerve growth factor (NGF). The angiogenesis process in the normal ovary is a tightly controlled process that occurs in each ovarian cycle. Also, angiogenesis is critical for ovarian cancer development and it is responsible for tumor spread, metastasis and its peritoneal dissemination. Ovarian cancer is the fifth leading cause of cancer death in women and it is distinguished as the most lethal gynecologic cancer. In recent years angiogenesis has been given considerable attention in order to identify targets for developing effective anti-tumor therapies. Several molecules have been reported to promote angiogenesis, such as platelet-derived growth factor (PDGF) and its receptors, the angiopoietin/Tie ligand/receptor system and fibroblast growth factor (FGF). Primarily, VEGF has been identified to play key roles in driving angiogenesis. The above-mentioned molecules are candidate drug targets. Used in combination with other treatments, anti-angiogenic therapies have managed to reduce disease progression. The present review is focused in NGF and its high affinity receptor tyrosine kinase A (TRKA). The expression of VEGF, proliferation and the angiogenesis process in ovarian cancer is importantly induced by NGF, among other molecules.

  14. Amplification of USP13 drives ovarian cancer metabolism

    PubMed Central

    Han, Cecil; Yang, Lifeng; Choi, Hyun Ho; Baddour, Joelle; Achreja, Abhinav; Liu, Yunhua; Li, Yujing; Li, Jiada; Wan, Guohui; Huang, Cheng; Ji, Guang; Zhang, Xinna; Nagrath, Deepak; Lu, Xiongbin

    2016-01-01

    Dysregulated energetic metabolism has been recently identified as a hallmark of cancer. Although mutations in metabolic enzymes hardwire metabolism to tumourigenesis, they are relatively infrequent in ovarian cancer. More often, cancer metabolism is re-engineered by altered abundance and activity of the metabolic enzymes. Here we identify ubiquitin-specific peptidase 13 (USP13) as a master regulator that drives ovarian cancer metabolism. USP13 specifically deubiquitinates and thus upregulates ATP citrate lyase and oxoglutarate dehydrogenase, two key enzymes that determine mitochondrial respiration, glutaminolysis and fatty acid synthesis. The USP13 gene is co-amplified with PIK3CA in 29.3% of high-grade serous ovarian cancers and its overexpression is significantly associated with poor clinical outcome. Inhibiting USP13 remarkably suppresses ovarian tumour progression and sensitizes tumour cells to the treatment of PI3K/AKT inhibitor. Our results reveal an important metabolism-centric role of USP13, which may lead to potential therapeutics targeting USP13 in ovarian cancers. PMID:27892457

  15. Senescent peritoneal mesothelium creates a niche for ovarian cancer metastases

    PubMed Central

    Mikuła-Pietrasik, Justyna; Uruski, Paweł; Sosińska, Patrycja; Maksin, Konstantin; Piotrowska-Kempisty, Hanna; Kucińska, Małgorzata; Murias, Marek; Szubert, Sebastian; Woźniak, Aldona; Szpurek, Dariusz; Sajdak, Stefan; Piwocka, Katarzyna; Tykarski, Andrzej; Książek, Krzysztof

    2016-01-01

    Although both incidence and aggressiveness of ovarian malignancy rise with age, the exact reason for this tendency, in particular the contribution of senescent cells, remains elusive. In this project we found that the patient's age determines the frequency of intraperitoneal metastases of ovarian cancer. Moreover, we documented that senescent human peritoneal mesothelial cells (HPMCs) stimulate proliferation, migration and invasion of ovarian cancer cells in vitro, and that this effect is related to both the activity of soluble agents released to the environment by these cells and direct cell-cell contact. The panel of mediators of the pro-cancerous activity of senescent HPMCs appeared to be cancer cell line-specific. The growth of tumors in a mouse peritoneal cavity was intensified when the cancer cells were co-injected together with senescent HPMCs. This effect was reversible when the senescence of HPMCs was slowed down by the neutralization of p38 MAPK. The analysis of lesions excised from the peritoneum of patients with ovarian cancer showed the abundance of senescent HPMCs in close proximity to the cancerous tissue. Collectively, our findings indicate that senescent HPMCs which accumulate in the peritoneum in vivo may create a metastatic niche facilitating intraperitoneal expansion of ovarian malignancy. PMID:28032864

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

    SciTech Connect

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

    2009-09-07

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

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

    PubMed Central

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

    2010-01-01

    The variability of radiation responses in ovarian tumors and tumor-derived cell lines is poorly understood. Since both DNA repair capacity and p53 status can significantly alter radiation sensitivity, we evaluated these factors along with radiation sensitivity in a panel of sporadic human ovarian carcinoma cell lines. We observed a gradation of radiation sensitivity among these sixteen lines, with a five-fold difference in the LD50 between the most radiosensitive and the most radioresistant cells. The DNA-dependent protein kinase (DNA-PK) is essential for the repair of radiation induced DNA double-strand breaks in human somatic cells. Therefore, we measured gene copy number, expression levels, protein abundance, genomic copy and kinase activity for DNA-PK in all of our cell lines. While there were detectable differences in DNA-PK between the cell lines, there was no clear correlation with any of these differences and radiation sensitivity. In contrast, p53 function as determined by two independent methods, correlated well with radiation sensitivity, indicating p53 mutant ovarian cancer cells are typically radioresistant relative to p53 wild-type lines. These data suggest that the activity of regulatory molecules such as p53 may be better indicators of radiation sensitivity than DNA repair enzymes such as DNA-PK in ovarian cancer. PMID:20204287

  18. Effects of deletion of the transcription factor Nrf2 and benzo[a]pyrene treatment on ovarian follicles and ovarian surface epithelial cells in mice

    PubMed Central

    Lim, Jinhwan; Ortiz, Laura; Nakamura, Brooke N.; Hoang, Yvonne D.; Banuelos, Jesus; Flores, Victoria N.; Chan, Jefferson Y.; Luderer, Ulrike

    2015-01-01

    Polycyclic aromatic hydrocarbons, like benzo[a]pyrene (BaP), are ubiquitous environmental pollutants and potent ovarian toxicants. The transcription factor NRF2 is an important regulator of the cellular response to electrophilic toxicants like BaP and to oxidative stress. NRF2 regulates transcription of genes involved in the detoxification of reactive metabolites of BaP and reactive oxygen species. We therefore hypothesized that Nrf2−/− mice have accelerated ovarian aging and increased sensitivity to the ovarian toxicity of BaP. A single injection of BaP dose-dependently depleted ovarian follicles in Nrf2+/+ and Nrf2−/− mice, but the effects of BaP were not enhanced in the absence of Nrf2. Similarly, Nrf2−/− mice did not have increased ovarian BaP DNA adduct formation compared to Nrf2+/+ mice. Ovarian follicle numbers did not differ between peripubertal Nrf2−/− and Nrf2+/+ mice, but by middle age, Nrf2−/− mice had significantly fewer primordial follicles than Nrf2+/+ mice, consistent with accelerated ovarian aging. PMID:26247513

  19. Longitudinal study of CEA and CA125 in ovarian cancer.

    PubMed

    Brioschi, P A; Bischof, P; Rapin, C; De Roten, M; Irion, O; Krauer, F

    1985-05-01

    Carcinoembrionic antigen (CEA) and cancer antigen 125 (Ca125) levels were measured at regular intervals over a 24-month period in 19 patients with proven ovarian cancers. In 91.5% of the cases with recurrent or progressive disease, Ca125 levels were increased whereas only 34% of these patients had increased CEA levels. Furthermore, reduction of the tumoral mass was associated with a decrease of Ca125 levels in all patients. It is proposed that determination of Ca125 levels in ovarian cancer might provide a valuable prognostic tool for the assessment of the evolution of the disease.

  20. Aurora-A Oncogene in Human Ovarian Cancer

    DTIC Science & Technology

    2006-11-01

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

  1. Flight and Analytical Methods for Determining the Coupled Vibration Response of Tandem Helicopters

    NASA Technical Reports Server (NTRS)

    Yeates, John E , Jr; Brooks, George W; Houbolt, John C

    1957-01-01

    Chapter one presents a discussion of flight-test and analysis methods for some selected helicopter vibration studies. The use of a mechanical shaker in flight to determine the structural response is reported. A method for the analytical determination of the natural coupled frequencies and mode shapes of vibrations in the vertical plane of tandem helicopters is presented in Chapter two. The coupled mode shapes and frequencies are then used to calculate the response of the helicopter to applied oscillating forces.

  2. 33 CFR Appendix C to Part 154 - Guidelines for Determining and Evaluating Required Response Resources for Facility Response Plans

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... refer to the applicable local contingency plan or ACP, as appropriate, to determine if ice, debris, and... the applicable response capability caps in Table 5 of this appendix shall identify sources of... contracting caps in Table 5 shall identify sources of additional equipment equal to twice the cap listed...

  3. 33 CFR Appendix C to Part 154 - Guidelines for Determining and Evaluating Required Response Resources for Facility Response Plans

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... refer to the applicable local contingency plan or ACP, as appropriate, to determine if ice, debris, and... the applicable response capability caps in Table 5 of this appendix shall identify sources of... contracting caps in Table 5 shall identify sources of additional equipment equal to twice the cap listed...

  4. 33 CFR Appendix C to Part 154 - Guidelines for Determining and Evaluating Required Response Resources for Facility Response Plans

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... refer to the applicable local contingency plan or ACP, as appropriate, to determine if ice, debris, and... the applicable response capability caps in Table 5 of this appendix shall identify sources of... contracting caps in Table 5 shall identify sources of additional equipment equal to twice the cap listed...

  5. 33 CFR Appendix C to Part 154 - Guidelines for Determining and Evaluating Required Response Resources for Facility Response Plans

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... refer to the applicable local contingency plan or ACP, as appropriate, to determine if ice, debris, and... the applicable response capability caps in Table 5 of this appendix shall identify sources of... contracting caps in Table 5 shall identify sources of additional equipment equal to twice the cap listed...

  6. Victim's Response and Alcohol-Related Factors as Determinants of Women's Responses to Violent Pornography

    ERIC Educational Resources Information Center

    Norris, Jeanette; Davis, Kelly Cue; George, William H.; Martell, Joel; Heiman, Julia R.

    2004-01-01

    Women suffer a variety of detrimental effects from exposure to violent pornography. This study examined the role of specific situational cues embedded within a violent pornographic story, as well as alcohol consumption and alcohol expectancies, to determine potential mechanisms through which these effects occur. Female social drinkers (N=123),…

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

    ClinicalTrials.gov

    2017-02-19

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

  8. Single-chain bifunctional vascular endothelial growth factor (VEGF)-follicle-stimulating hormone (FSH)-C-terminal peptide (CTP) is superior to the combination therapy of recombinant VEGF plus FSH-CTP in stimulating angiogenesis during ovarian folliculogenesis.

    PubMed

    Trousdale, Rhonda K; Pollak, Susan V; Klein, Jeffrey; Lobel, Leslie; Funahashi, Yasuhiro; Feirt, Nikki; Lustbader, Joyce W

    2007-03-01

    Infertility technologies often employ exogenous gonadotropin therapy to increase antral follicle production. In an effort to enhance ovarian response, several long-acting FSH therapies have been developed including an FSH-C-terminal peptide (CTP), where the FSH subunits are linked by the CTP moiety from human chorionic gonadotropin, which is responsible for the increased half-life of human chorionic gonadotropin. We found that administration of FSH-CTP for ovarian hyperstimulation in rats blunted ovarian follicle vascular development. In women, reduced ovarian vasculature has been associated with lower pregnancy rates. We were interested in determining whether vascular endothelial growth factor (VEGF) therapy could enhance ovarian angiogenesis in FSH-CTP-treated rats. Coadministration of systemic FSH-CTP plus recombinant VEGF was compared with treatment with a novel, single-chain bifunctional VEGF-FSH-CTP (VFC) analog. For VFC, the FSH portion targets the protein to the ovary and stimulates follicle growth, whereas VEGF enhances local vascular development. Both in vitro and in vivo studies confirm the dual FSH and VEGF action of the VFC protein. Evaluation of ovarian follicle development demonstrates that administration of combination therapy using VEGF and FSH-CTP failed to increase follicle vasculature above levels seen with FSH-CTP monotherapy. However, treatment with VFC significantly increased follicle vascular development while concurrently increasing the number of large antral follicles produced. In conclusion, we report the production and characterization of a long-acting, bifunctional VEGF-FSH-CTP protein that is superior to combination therapy for enhancing VEGF activity in the ovary and stimulating follicular angiogenesis in rats.

  9. [Peripubertal ovarian cyst torsion as an early complication of undiagnosed polycystic ovarian syndrome].

    PubMed

    Ságodi, László; Schmidt, Ildikó; Vámosi, Ildikó; Barkai, László

    2013-01-20

    The aim of the authors is to present two cases which raise the possibility of an association between polycystic ovarian syndrome/hyperandrogenism and ovarian cyst torsion in peripubertal girls. Androgen excess may cause more frequently ovarian cyst formation in premenarcheal or young adolescents with undiagnosed polycystic ovarian syndrome than in adults. The authors recommend that polycystic ovarian syndrome as well as late onset congenital adrenal hyperplasia should be considered in peripubertal adolescents with ovarian cyst torsion. In case polycystic ovarian syndrome is confirmed, adequate management according to age and pubertal development of the patients should be commenced.

  10. Do We Know What Causes Ovarian Cancer?

    MedlinePlus

    ... stromal tumors of the ovaries. There are many theories about the causes of ovarian cancer. Some of ... hysterectomy lower the risk of ovarian cancer. One theory to explain this is that some cancer-causing ...

  11. Proteomic analysis of temporally stimulated ovarian cancer cells for biomarker discovery.

    PubMed

    Marzinke, Mark A; Choi, Caitlin H; Chen, Li; Shih, Ie-Ming; Chan, Daniel W; Zhang, Hui

    2013-02-01

    While ovarian cancer remains the most lethal gynecological malignancy in the United States, there are no biomarkers available that are able to predict therapeutic responses to ovarian malignancies. One major hurdle in the identification of useful biomarkers has been the ability to obtain enough ovarian cancer cells from primary tissues diagnosed in the early stages of serous carcinomas, the most deadly subtype of ovarian tumor. In order to detect ovarian cancer in a state of hyperproliferation, we analyzed the implications of molecular signaling cascades in the ovarian cancer cell line OVCAR3 in a temporal manner, using a mass-spectrometry-based proteomics approach. OVCAR3 cells were treated with EGF(1), and the time course of cell progression was monitored based on Akt phosphorylation and growth dynamics. EGF-stimulated Akt phosphorylation was detected at 12 h post-treatment, but an effect on proliferation was not observed until 48 h post-exposure. Growth-stimulated cellular lysates were analyzed for protein profiles between treatment groups and across time points using iTRAQ labeling and mass spectrometry. The protein response to EGF treatment was identified via iTRAQ analysis in EGF-stimulated lysates relative to vehicle-treated specimens across the treatment time course. Validation studies were performed on one of the differentially regulated proteins, lysosomal-associated membrane protein 1 (LAMP-1), in human tissue lysates and ovarian tumor tissue sections. Further, tissue microarray analysis was performed to demarcate LAMP-1 expression across different stages of epithelial ovarian cancers. These data support the use of this approach for the efficient identification of tissue-based markers in tumor development related to specific signaling pathways. LAMP-1 is a promising biomarker for studies of the progression of EGF-stimulated ovarian cancers and might be useful in predicting treatment responses involving tyrosine kinase inhibitors or EGF receptor

  12. ERBB4 Expression in Ovarian Serous Carcinoma Resistant to Platinum-Based Therapy.

    PubMed

    Saglam, Ozlen; Xiong, Yin; Marchion, Douglas C; Strosberg, Carolina; Wenham, Robert M; Johnson, Joseph J; Saeed-Vafa, Daryoush; Cubitt, Christopher; Hakam, Ardeshir; Magliocco, Anthony M

    2017-01-01

    Few data exist on the prognostic and predictive impact of erb-b2 receptor tyrosine kinase 4 (ERBB4) in ovarian cancer. Thus, we evaluated ERBB4 expression by immunohistochemistry in a tumor microarray consisting of 100 ovarian serous carcinoma specimens (50 complete responses [CRs] and 50 incomplete responses [IRs] to platinum-based therapy), 51 normal tissue controls, and 16 ovarian cancer cell lines. H scores were used to evaluate expression and were semiquantitatively classified into low, intermediate, and high categories. Category frequencies were compared between tumor specimens vs controls using an unpaired t test. Among tumors, category frequencies were compared between CR and IR to chemotherapy. Overall survival (OS) was stratified by category. In total, 74 ovarian serous carcinoma samples (32 CRs and 42 IRs), 28 normal controls, and 16 ovarian cancer cell lines were evaluable. High-level ERBB4 expression was observed at a significantly higher frequency in ovarian serous carcinoma compared with normal control tissue. Among tumor specimens, ERBB4 expression was significantly higher for those with an IR to chemotherapy compared with CR (P = .033). OS was inversely correlated with ERBB4 expression levels. Median rates of OS were 18, 22, and 58 months among high-, intermediate-, and low-expression tumors, respectively. Our results indicate that ERBB4 expression by immunohistochemistry may correlate with chemotherapy-resistant ovarian serous carcinoma and shortened OS.

  13. Protective role for ovarian glutathione S-transferase isoform pi during 7,12-dimethylbenz[a]anthracene-induced ovotoxicity

    SciTech Connect

    Bhattacharya, Poulomi Keating, Aileen F.

    2012-04-15

    7,12-Dimethylbenz[a]anthracene (DMBA) destroys ovarian follicles at all developmental stages. This study investigated a role for the glutathione S-transferase (Gst) isoforms alpha (a), mu (m) and pi (p) and the transcription factors, Ahr and Nrf2, during DMBA-induced ovotoxicity, and their regulation by phosphatidylinositol-3 kinase (PI3K) signaling. Negative regulation of JNK by GSTP during DMBA exposure was also studied. Post-natal day (PND) 4 Fischer 344 rat ovaries were exposed to vehicle control (1% DMSO) ± DMBA (1 μM) or vehicle control (1% DMSO) ± LY294002 (PI3K inhibitor; 20 μM) for 1, 2, 4, or 6 days. Total RNA or protein was isolated, followed by RT-PCR or Western blotting to determine mRNA or protein level, respectively. Immunoprecipitation using an anti-GSTP antibody was performed to determine interaction between GSTP and JNK, followed by Western blotting to determine JNK and p-c-Jun protein level. DMBA had no impact on Gsta, Gstm or Nrf2 mRNA level, but increased Gstp mRNA and protein after 2 days. Ahr mRNA and protein increased after 2 and 4 days of DMBA exposure, respectively and DMBA increased NRF2 protein level after 4 days. JNK bound to GSTP was increased during DMBA exposure, with a concomitant decrease in unbound JNK and p-c-Jun. Ahr and Gstp mRNA were decreased (2 days) and increased (4 days) by PI3K inhibition, while Gstm mRNA increased (P < 0.05) after both time points, and there was no effect on Nrf2 mRNA. PI3K inhibition increased AHR, NRF2 and GSTP protein level. These findings support involvement of ovarian GSTP during DMBA exposure, and indicate a regulatory role for the PI3K signaling pathway on ovarian xenobiotic metabolism gene expression. -- Highlights: ► Ovarian GSTP is activated in response to DMBA exposure. ► AhR and Nrf2 transcription factors are up-regulated by DMBA. ► PI3K signaling regulates Ahr, Nrf2 and Gstp expression. ► GSTP negatively regulates ovarian JNK in response to DMBA exposure.

  14. Determination of individual stimulus--response curves in the visual cortex.

    PubMed

    Hagenbeek, Rogier E; Rombouts, Serge A R B; van Dijk, Bob W; Barkhof, Frederik

    2002-12-01

    Activation in the visual cortex is typically studied using group average changes in an on-off paradigm for a single flicker frequency. We used functional magnetic resonance imaging (fMRI) to characterize the stimulus-response curve in the visual cortex as a function of flicker frequency in individual subjects, using LED goggles with 17 frequency steps between 0 and 30 Hz. Ten healthy young individuals were studied on two different occasions (mean interval; 22 days). In all but one subject, a third-order polynomial curve could be fitted to the data. From the response curve we calculated the peak response (the frequency where the response amplitude was maximal), the percentage change (relative difference) of the response amplitudes between 8 Hz and the peak frequency, and the average slope of response (towards the peak). On both occasions we could determine a peak response for each subject with small within-subject variability. The average absolute difference in peak response between both sessions was 1.37 Hz (range, 0.2-4.3 Hz), indicating that the peak frequency is rather stable for a given individual. In conclusion, our study illustrates the ability of fMRI to examine the stimulus-response curve in individual subjects in the visual cortex. Based on our findings, the peak response and the slope of response seem highly reproducible within subjects. A similar analysis of the stimulus-response curve may be applicable to other types of stimuli.

  15. GnRH Analogues in the Prevention of Ovarian Hyperstimulation Syndrome

    PubMed Central

    Alama, Pilar; Bellver, Jose; Vidal, Carmen; Giles, Juan

    2013-01-01

    The GnRH analogue (agonist and antagonist GnRH) changed ovarian stimulation. On the one hand, it improved chances of pregnancy to obtain more oocytes and better embryos. This leads to an ovarian hyper-response, which can be complicated by the ovarian hyperstimulation syndrome (OHSS). On the other hand, the GnRH analogue can prevent the incidence of OHSS: GnRH antagonist protocols, GnRH agonist for triggering final oocyte maturation, either together or separately, coasting, and the GnRH analogue may prove useful for avoiding OHSS in high-risk patients. We review these topics in this article. PMID:23825982

  16. Ovarian teratoma and endometritis in a mare

    PubMed Central

    2005-01-01

    Abstract An 8-year-old Arabian mare was admitted for a large ovarian anovulatory follicle. A clinical diagnosis of ovarian tumor and endometritis was established. Histological examinations revealed an ovarian teratoma and a grade II endometritis. Three months after unilateral ovariectomy, the mare was confirmed pregnant and eventually gave birth uneventfully. PMID:16363331

  17. BRCA2 Polymorphic Stop Codon K3326X and the Risk of Breast, Prostate, and Ovarian Cancers

    PubMed Central

    Meeks, Huong D.; Song, Honglin; Michailidou, Kyriaki; Bolla, Manjeet K.; Dennis, Joe; Wang, Qin; Barrowdale, Daniel; Frost, Debra; McGuffog, Lesley; Ellis, Steve; Feng, Bingjian; Buys, Saundra S.; Hopper, John L.; Southey, Melissa C.; Tesoriero, Andrea; James, Paul A.; Bruinsma, Fiona; Campbell, Ian G.; Broeks, Annegien; Schmidt, Marjanka K.; Hogervorst, Frans B. L.; Beckman, Matthias W.; Fasching, Peter A.; Fletcher, Olivia; Johnson, Nichola; Sawyer, Elinor J.; Riboli, Elio; Banerjee, Susana; Menon, Usha; Tomlinson, Ian; Burwinkel, Barbara; Hamann, Ute; Marme, Frederik; Rudolph, Anja; Janavicius, Ramunas; Tihomirova, Laima; Tung, Nadine; Garber, Judy; Cramer, Daniel; Terry, Kathryn L.; Poole, Elizabeth M.; Tworoger, Shelley S.; Dorfling, Cecilia M.; van Rensburg, Elizabeth J.; Godwin, Andrew K.; Guénel, Pascal; Truong, Thérèse; Stoppa-Lyonnet, Dominique; Damiola, Francesca; Mazoyer, Sylvie; Sinilnikova, Olga M.; Isaacs, Claudine; Maugard, Christine; Bojesen, Stig E.; Flyger, Henrik; Gerdes, Anne-Marie; Hansen, Thomas V. O.; Jensen, Allen; Kjaer, Susanne K.; Hogdall, Claus; Hogdall, Estrid; Pedersen, Inge Sokilde; Thomassen, Mads; Benitez, Javier; González-Neira, Anna; Osorio, Ana; de la Hoya, Miguel; Segura, Pedro Perez; Diez, Orland; Lazaro, Conxi; Brunet, Joan; Anton-Culver, Hoda; Eunjung, Lee; John, Esther M.; Neuhausen, Susan L.; Ding, Yuan Chun; Castillo, Danielle; Weitzel, Jeffrey N.; Ganz, Patricia A.; Nussbaum, Robert L.; Chan, Salina B.; Karlan, Beth Y.; Lester, Jenny; Wu, Anna; Gayther, Simon; Ramus, Susan J.; Sieh, Weiva; Whittermore, Alice S.; Monteiro, Alvaro N. A.; Phelan, Catherine M.; Terry, Mary Beth; Piedmonte, Marion; Offit, Kenneth; Robson, Mark; Levine, Douglas; Moysich, Kirsten B.; Cannioto, Rikki; Olson, Sara H.; Daly, Mary B.; Nathanson, Katherine L.; Domchek, Susan M.; Lu, Karen H.; Liang, Dong; Hildebrant, Michelle A. T.; Ness, Roberta; Modugno, Francesmary; Pearce, Leigh; Goodman, Marc T.; Thompson, Pamela J.; Brenner, Hermann; Butterbach, Katja; Meindl, Alfons; Hahnen, Eric; Wappenschmidt, Barbara; Brauch, Hiltrud; Brüning, Thomas; Blomqvist, Carl; Khan, Sofia; Nevanlinna, Heli; Pelttari, Liisa M.; Aittomäki, Kristiina; Butzow, Ralf; Bogdanova, Natalia V.; Dörk, Thilo; Lindblom, Annika; Margolin, Sara; Rantala, Johanna; Kosma, Veli-Matti; Mannermaa, Arto; Lambrechts, Diether; Neven, Patrick; Claes, Kathleen B. M.; Maerken, Tom Van; Chang-Claude, Jenny; Flesch-Janys, Dieter; Heitz, Florian; Varon-Mateeva, Raymonda; Peterlongo, Paolo; Radice, Paolo; Viel, Alessandra; Barile, Monica; Peissel, Bernard; Manoukian, Siranoush; Montagna, Marco; Oliani, Cristina; Peixoto, Ana; Teixeira, Manuel R.; Collavoli, Anita; Hallberg, Emily; Olson, Janet E.; Goode, Ellen L.; Hart, Steven N.; Shimelis, Hermela; Cunningham, Julie M.; Giles, Graham G.; Milne, Roger L.; Healey, Sue; Tucker, Kathy; Haiman, Christopher A.; Henderson, Brian E.; Goldberg, Mark S.; Tischkowitz, Marc; Simard, Jacques; Soucy, Penny; Eccles, Diana M.; Le, Nhu; Borresen-Dale, Anne-Lise; Kristensen, Vessela; Salvesen, Helga B.; Bjorge, Line; Bandera, Elisa V.; Risch, Harvey; Zheng, Wei; Beeghly-Fadiel, Alicia; Cai, Hui; Pylkäs, Katri; Tollenaar, Robert A. E. M.; van der Ouweland, Ans M. W.; Andrulis, Irene L.; Knight, Julia A.; Narod, Steven; Devilee, Peter; Winqvist, Robert; Figueroa, Jonine; Greene, Mark H.; Mai, Phuong L.; Loud, Jennifer T.; García-Closas, Montserrat; Schoemaker, Minouk J.; Czene, Kamila; Darabi, Hatef; McNeish, Iain; Siddiquil, Nadeem; Glasspool, Rosalind; Kwong, Ava; Park, Sue K.; Teo, Soo Hwang; Yoon, Sook-Yee; Matsuo, Keitaro; Hosono, Satoyo; Woo, Yin Ling; Gao, Yu-Tang; Foretova, Lenka; Singer, Christian F.; Rappaport-Feurhauser, Christine; Friedman, Eitan; Laitman, Yael; Rennert, Gad; Imyanitov, Evgeny N.; Hulick, Peter J.; Olopade, Olufunmilayo I.; Senter, Leigha; Olah, Edith; Doherty, Jennifer A.; Schildkraut, Joellen; Koppert, Linetta B.; Kiemeney, Lambertus A.; Massuger, Leon F. A. G.; Cook, Linda S.; Pejovic, Tanja; Li, Jingmei; Borg, Ake; Öfverholm, Anna; Rossing, Mary Anne; Wentzensen, Nicolas; Henriksson, Karin; Cox, Angela; Cross, Simon S.; Pasini, Barbara J.; Shah, Mitul; Kabisch, Maria; Torres, Diana; Jakubowska, Anna; Lubinski, Jan; Gronwald, Jacek; Agnarsson, Bjarni A.; Kupryjanczyk, Jolanta; Moes-Sosnowska, Joanna; Fostira, Florentia; Konstantopoulou, Irene; Slager, Susan; Jones, Michael; Antoniou, Antonis C.; Berchuck, Andrew; Swerdlow, Anthony; Chenevix-Trench, Georgia; Dunning, Alison M.; Pharoah, Paul D. P.; Hall, Per; Easton, Douglas F.

    2016-01-01

    Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations. PMID:26586665

  18. Global ovarian cancer health disparities

    PubMed Central

    Chornokur, Ganna; Amankwah, Ernest K.; Schildkraut, Joellen M.; Phelan, Catherine M.

    2013-01-01

    Objective The objective of this article is to broadly review the scientific literature and summarize the most up-to-date findings on ovarian cancer health disparities worldwide and in the United States (U.S.). Methods The present literature on disparities in ovarian cancer was reviewed. Original research and relevant review articles were included. Results Ovarian cancer health disparities exist worldwide and in the U.S. Ovarian cancer disproportionately affect African American women at all stages of the disease, from presentation through treatment, and ultimately increased mortality and decreased survival, compared to non-Hispanic White women. Increased mortality is likely to be explained by unequal access to care and non-standard treatment regimens frequently administered to African American women, but may also be attributed to genetic susceptibility, acquired co-morbid conditions and increased frequency of modifiable risk factors, albeit to substantially lesser extent. Unequal access to care is, in turn, largely a consequence of lower socioeconomic status and lack of private health insurance coverage among the African American population. Conclusions Our findings suggest the need for policy changes aimed at facilitating equal access to quality medical care. At the same time, further research is necessary to fully resolve racial disparities in ovarian cancer. PMID:23266352

  19. Elesclomol Sodium and Paclitaxel in Treating Patients With Recurrent or Persistent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2014-12-23

    Malignant Ovarian Mixed Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Ovarian Carcinoma

  20. Paclitaxel, Cisplatin, and Topotecan With or Without Filgrastim in Treating Patients With Newly Diagnosed Stage III or Stage IV Epithelial Ovarian Cancer

    ClinicalTrials.gov

    2013-01-23

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

  1. TLR8 Agonist VTX-2337 and Pegylated Liposomal Doxorubicin Hydrochloride or Paclitaxel in Treating Patients With Recurrent or Persistent Ovarian Epithelial, Fallopian Tube, or Peritoneal Cavity Cancer

    ClinicalTrials.gov

    2014-12-23

    Malignant Ovarian Mixed Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Ovarian Carcinoma

  2. Resveratrol-induced autophagocytosis in ovarian cancer cells.

    PubMed

    Opipari, Anthony W; Tan, Lijun; Boitano, Anthony E; Sorenson, Dorothy R; Aurora, Anjili; Liu, J Rebecca

    2004-01-15

    Resveratrol (3,5,4-trihydroxystilbene), a natural phytoalexin present in grapes, nuts, and red wine, has antineoplastic activities. Several molecular mechanisms have been described to underlie its effects on cells in vitro and in vivo. In the present study, the response of ovarian cancer cells to resveratrol is explored. Resveratrol inhibited growth and induced death in a panel of five human ovarian carcinoma cell lines. The response was associated with mitochondrial release of cytochrome c, formation of the apoptosome complex, and caspase activation. Surprisingly, even with these molecular features of apoptosis, analysis of resveratrol-treated cells by light and electron microscopy revealed morphology and ultrastructural changes indicative of autophagocytic, rather than apoptotic, death. This suggests that resveratrol can induce cell death through two distinct pathways. Consistent with resveratrol's ability to kill cells via nonapoptotic processes, cells transfected to express high levels of the antiapoptotic proteins Bcl-x(L) and Bcl-2 are equally sensitive as control cells to resveratrol. Together, these findings show that resveratrol induces cell death in ovarian cancer cells through a mechanism distinct from apoptosis, therefore suggesting that it may provide leverage to treat ovarian cancer that is chemoresistant on the basis of ineffective apoptosis.

  3. The immunomodulating roles of glycoproteins in epithelial ovarian cancer

    PubMed Central

    Patankar, Manish S.; Gubbels, Jennifer A.A.; Felder, Mildred; Connor, Joseph P.

    2015-01-01

    The complexity of the immune system demands an intricate defense mechanism by tumors. Ovarian and other tumors employ specific glycoproteins and the associated glycan sequences to modulate immune responses. Glycoproteins enable tumor cells that express or secrete these molecules to evade immune cell attack and induce the immune system to promote tumor growth. This review focuses first on the immune environment in ovarian cancer, and the mechanisms of activation and inhibition that immune cells undergo in order to either attack or ignore a target cell. Next we illustrate the immunomodulatory roles of ovarian cancer-associated glycans and glycoproteins in 1. preventing immune synapse formation, 2. serving as ligands of immune cell receptors, 3. scavenging cytokines and chemokines, and 4. participating in the formation of autoantibodies against the tumor. The importance of these immunomodulating strategies from the view points of understanding the tumor immunology of ovarian tumors, potential origin of such mechanisms, and specific strategies to circumvent the glycoconjugate-mediated suppression of immune responses is discussed in this review. PMID:22201900

  4. Ovarian Cancer in Ghana, a 10 Year Histopathological Review of Cases at Korle Bu Teaching Hospital.

    PubMed

    Akakpo, Patrick K; Derkyi-Kwarteng, Leonard; Gyasi, Richard K; Quayson, Solomon E; Anim, Jehoram T

    2015-12-01

    To determine the histopathological types, age distribution, presenting signs and symptoms of ovarian cancers diagnosed at the Korle-Bu Teaching Hospital, Ghana. All histopathology slides and request cards of ovarian cancers diagnosed over a ten-year period (2001 to 2010) were reviewed and the cancers classified according to the World Health Organization 1999 classification. Biographical and clinical data of the patients were collected and results entered into Epi-info to determine the frequency, age distribution and clinical presentation of the various types of ovarian cancer. There were 192 (27.2%) ovarian cancers out of 706 ovarian tumours. Epithelial cancers were the most common: 100 (52.1%), followed by sex cord stromal cancers 66 (34.4%). Majority of epithelial cancers were serous adenocarcinomas (71/100) while most sex cord stromal cancers were adult granulosa cell tumours 46 (69.7%). The mean age of patients with adenocarcinoma was 49 years while that of the 46 adult granulosa cell tumours was 46.5 years. Patients present with varying combinations of symptoms and signs and ovarian cancers present at an earlier age compared to other populations, with the age of presentation being slightly lower for sex cord stromal cancers compared to adenocarcinomas. There are no specific symptoms or signs associated with ovarian cancer at presentation, to assist with diagnosis.

  5. Comparison of pregnancy outcome after letrozole versus clomiphene treatment for mild ovarian stimulation protocol in poor responders

    PubMed Central

    Eftekhar, Maryam; Mohammadian, Farnaz; Davar, Robab; Pourmasumi, Soheila

    2014-01-01

    Background: Poor ovarian response to controlled ovarian stimulation is one of the most important interest points in assisted reproduction. Mild ovarian stimulation seems to be preferable to high dose of FSH regimens in women with a history of poor ovarian response in previous protocol. Clomiphene citrate and letrozole alone or in combination with FSH have been used in mild ovarian stimulation protocol. Objective: To compare the efficacy of letrozole and clomiphene citrate for mild ovarian stimulation on assisted reproductive technology outcomes in poor responders. Materials and Methods: In a randomized control study, 184 women aged between 20 and 45 years with the history of poor response to ovarian stimulation who were candidate for ART were randomly subdivided into two groups: group I (n= 80), women who underwent the clomiphene/gonadotropin/antagonist protocol; and group II (n= 87), patients who underwent the letrozole/gonadotropin/antagonist protocol. Groups were compared regarding implantation, chemical and clinical pregnancy rates. Results: There was a significant difference in the mean endometrial thickness between two groups (9.16±1.2 mm vs. 8.3±0.3 mm). The implantation rate was significantly higher in letrozole group compare to clomiphene group (7.2 vs. 6.6%, p=0.024 respectively). No significant differences were found in chemical and clinical pregnancy rate between two groups. Conclusion: In mild ovarian stimulation protocol, letrozole and clomiphene have similar value for the poor responder. The optimal treatment strategy for these patients remains debated. PMID:25709627

  6. A Systematic Review of Ovarian Cancer and Fear of Recurrence

    PubMed Central

    Ozga, Melissa; Aghajanian, Carol; Myers-Virtue, Shannon; McDonnell, Glynnis; Jhanwar, Sabrina; Hichenberg, Shira; Sulimanoff, Isabel

    2016-01-01

    Objective To assess demographic, medical and psychological factors that are associated with fear of recurrence (FCR) in ovarian cancer patients. Methods We searched PubMed, EMBASE, Cochrane, CINAHL, and PsycINFO. For PubMed, a search using Medical Subject Headings (MeSH) was run, as well as a textword search from 1990 to July 2014. Search terms that were used consisted of ovarian terms, fear terms, and recurrence/progression themes. Title and abstract reviews were conducted by two independent reviewers to determine eligibility, and discrepancies were decided by a third reviewer. Full-text reviews of potentially eligible articles were conducted by the review team, which met regularly to ensure the reliability of eligibility ratings across all articles. Results Fifteen articles met our inclusion criteria. Nine were quantitative studies that utilized a cross-sectional design, and six studies consisted of three qualitative studies, two small intervention studies, and one study that utilized content analysis to explore written correspondence among ovarian cancer patients. FCR was reported as a significant concern for both older and younger women at both early and advanced stages. Women were distressed about recurrence at various times during their treatment and post-treatment. FCR was noted to be prevalent around cancer follow-up examinations. Many women report not receiving adequate support for recurrence. FCR was also shown to be linked in some way to hopelessness, faith/spirituality, and PTSD. FCR was also linked to patients’ anxiety about death and dying and the uncertainty of the future of their medical health. Conclusions This review demonstrates that FCR is prevalent in the ovarian cancer population. Cancer recurrence fears are not adequately assessed or treated. More information is needed on the factors that may be related to women’s fears about recurrence in the ovarian cancer population. In addition, a validated measure of FCR among ovarian cancer patients

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

    PubMed Central

    Lu, Yi; Cuellar-Partida, Gabriel; Painter, Jodie N.; Nyholt, Dale R.; Morris, Andrew P.; Fasching, Peter A.; Hein, Alexander; Burghaus, Stefanie; Beckmann, Matthias W.; Lambrechts, Diether; Van Nieuwenhuysen, Els; Vergote, Ignace; Vanderstichele, Adriaan; Doherty, Jennifer Anne; Rossing, Mary Anne; Wicklund, Kristine G.; Chang-Claude, Jenny; Eilber, Ursula; Rudolph, Anja; Wang-Gohrke, Shan; Goodman, Marc T.; Bogdanova, Natalia; Dörk, Thilo; Dürst, Matthias; Hillemanns, Peter; Runnebaum, Ingo B.; Antonenkova, Natalia; Butzow, Ralf; Leminen, Arto; Nevanlinna, Heli; Pelttari, Liisa M.; Edwards, Robert P.; Kelley, Joseph L.; Modugno, Francesmary; Moysich, Kirsten B.; Ness, Roberta B.; Cannioto, Rikki; Høgdall, Estrid; Jensen, Allan; Giles, Graham G.; Bruinsma, Fiona; Kjaer, Susanne K.; Hildebrandt, Michelle A.T.; Liang, Dong; Lu, Karen H.; Wu, Xifeng; Bisogna, Maria; Dao, Fanny; Levine, Douglas A.; Cramer, Daniel W.; Terry, Kathryn L.; Tworoger, Shelley S.; Missmer, Stacey; Bjorge, Line; Salvesen, Helga B.; Kopperud, Reidun K.; Bischof, Katharina; Aben, Katja K.H.; Kiemeney, Lambertus A.; Massuger, Leon F.A.G.; Brooks-Wilson, Angela; Olson, Sara H.; McGuire, Valerie; Rothstein, Joseph H.; Sieh, Weiva; Whittemore, Alice S.; Cook, Linda S.; Le, Nhu D.; Gilks, C. Blake; Gronwald, Jacek; Jakubowska, Anna; Lubiński, Jan; Gawełko, Jan; Song, Honglin; Tyrer, Jonathan P.; Wentzensen, Nicolas; Brinton, Louise; Trabert, Britton; Lissowska, Jolanta; Mclaughlin, John R.; Narod, Steven A.; Phelan, Catherine; Anton-Culver, Hoda; Ziogas, Argyrios; Eccles, Diana; Gayther, Simon A.; Gentry-Maharaj, Aleksandra; Menon, Usha; Ramus, Susan J.; Wu, Anna H.; Dansonka-Mieszkowska, Agnieszka; Kupryjanczyk, Jolanta; Timorek, Agnieszka; Szafron, Lukasz; Cunningham, Julie M.; Fridley, Brooke L.; Winham, Stacey J.; Bandera, Elisa V.; Poole, Elizabeth M.; Morgan, Terry K.; Risch, Harvey A.; Goode, Ellen L.; Schildkraut, Joellen M.; Webb, Penelope M.; Pearce, Celeste L.; Berchuck, Andrew; Pharoah, Paul D.P.; Montgomery, Grant W.; Zondervan, Krina T.; Chenevix-Trench, Georgia; MacGregor, Stuart

    2015-01-01

    Epidemiological studies have demonstrated associations between endometriosis and certain histotypes of ovarian cancer, including clear cell, low-grade serous and endometrioid carcinomas. We aimed to determine whether the observed associations might be due to shared genetic aetiology. To address this, we used two endometriosis datasets genotyped on common arrays with full-genome coverage (3194 cases and 7060 controls) and a large ovarian cancer dataset genotyped on the customized Illumina Infinium iSelect (iCOGS) arrays (10 065 cases and 21 663 controls). Previous work has suggested that a large number of genetic variants contribute to endometriosis and ovarian cancer (all histotypes combined) susceptibility. Here, using the iCOGS data, we confirmed polygenic architecture for most histotypes of ovarian cancer. This led us to evaluate if the polygenic effects are shared across diseases. We found evidence for shared genetic risks between endometriosis and all histotypes of ovarian cancer, except for the intestinal mucinous type. Clear cell carcinoma showed the strongest genetic correlation with endometriosis (0.51, 95% CI = 0.18–0.84). Endometrioid and low-grade serous carcinomas had similar correlation coefficients (0.48, 95% CI = 0.07–0.89 and 0.40, 95% CI = 0.05–0.75, respectively). High-grade serous carcinoma, which often arises from the fallopian tubes, showed a weaker genetic correlation with endometriosis (0.25, 95% CI = 0.11–0.39), despite the absence of a known epidemiological association. These results suggest that the epidemiological association between endometriosis and ovarian adenocarcinoma may be attributable to shared genetic susceptibility loci. PMID:26231222

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

    PubMed

    Lu, Yi; Cuellar-Partida, Gabriel; Painter, Jodie N; Nyholt, Dale R; Morris, Andrew P; Fasching, Peter A; Hein, Alexander; Burghaus, Stefanie; Beckmann, Matthias W; Lambrechts, Diether; Van Nieuwenhuysen, Els; Vergote, Ignace; Vanderstichele, Adriaan; Doherty, Jennifer Anne; Rossing, Mary Anne; Wicklund, Kristine G; Chang-Claude, Jenny; Eilber, Ursula; Rudolph, Anja; Wang-Gohrke, Shan; Goodman, Marc T; Bogdanova, Natalia; Dörk, Thilo; Dürst, Matthias; Hillemanns, Peter; Runnebaum, Ingo B; Antonenkova, Natalia; Butzow, Ralf; Leminen, Arto; Nevanlinna, Heli; Pelttari, Liisa M; Edwards, Robert P; Kelley, Joseph L; Modugno, Francesmary; Moysich, Kirsten B; Ness, Roberta B; Cannioto, Rikki; Høgdall, Estrid; Jensen, Allan; Giles, Graham G; Bruinsma, Fiona; Kjaer, Susanne K; Hildebrandt, Michelle A T; Liang, Dong; Lu, Karen H; Wu, Xifeng; Bisogna, Maria; Dao, Fanny; Levine, Douglas A; Cramer, Daniel W; Terry, Kathryn L; Tworoger, Shelley S; Missmer, Stacey; Bjorge, Line; Salvesen, Helga B; Kopperud, Reidun K; Bischof, Katharina; Aben, Katja K H; Kiemeney, Lambertus A; Massuger, Leon F A G; Brooks-Wilson, Angela; Olson, Sara H; McGuire, Valerie; Rothstein, Joseph H; Sieh, Weiva; Whittemore, Alice S; Cook, Linda S; Le, Nhu D; Gilks, C Blake; Gronwald, Jacek; Jakubowska, Anna; Lubiński, Jan; Gawełko, Jan; Song, Honglin; Tyrer, Jonathan P; Wentzensen, Nicolas; Brinton, Louise; Trabert, Britton; Lissowska, Jolanta; Mclaughlin, John R; Narod, Steven A; Phelan, Catherine; Anton-Culver, Hoda; Ziogas, Argyrios; Eccles, Diana; Gayther, Simon A; Gentry-Maharaj, Aleksandra; Menon, Usha; Ramus, Susan J; Wu, Anna H; Dansonka-Mieszkowska, Agnieszka; Kupryjanczyk, Jolanta; Timorek, Agnieszka; Szafron, Lukasz; Cunningham, Julie M; Fridley, Brooke L; Winham, Stacey J; Bandera, Elisa V; Poole, Elizabeth M; Morgan, Terry K; Risch, Harvey A; Goode, Ellen L; Schildkraut, Joellen M; Webb, Penelope M; Pearce, Celeste L; Berchuck, Andrew; Pharoah, Paul D P; Montgomery, Grant W; Zondervan, Krina T; Chenevix-Trench, Georgia; MacGregor, Stuart

    2015-10-15

    Epidemiological studies have demonstrated associations between endometriosis and certain histotypes of ovarian cancer, including clear cell, low-grade serous and endometrioid carcinomas. We aimed to determine whether the observed associations might be due to shared genetic aetiology. To address this, we used two endometriosis datasets genotyped on common arrays with full-genome coverage (3194 cases and 7060 controls) and a large ovarian cancer dataset genotyped on the customized Illumina Infinium iSelect (iCOGS) arrays (10 065 cases and 21 663 controls). Previous work has suggested that a large number of genetic variants contribute to endometriosis and ovarian cancer (all histotypes combined) susceptibility. Here, using the iCOGS data, we confirmed polygenic architecture for most histotypes of ovarian cancer. This led us to evaluate if the polygenic effects are shared across diseases. We found evidence for shared genetic risks between endometriosis and all histotypes of ovarian cancer, except for the intestinal mucinous type. Clear cell carcinoma showed the strongest genetic correlation with endometriosis (0.51, 95% CI = 0.18-0.84). Endometrioid and low-grade serous carcinomas had similar correlation coefficients (0.48, 95% CI = 0.07-0.89 and 0.40, 95% CI = 0.05-0.75, respectively). High-grade serous carcinoma, which often arises from the fallopian tubes, showed a weaker genetic correlation with endometriosis (0.25, 95% CI = 0.11-0.39), despite the absence of a known epidemiological association. These results suggest that the epidemiological association between endometriosis and ovarian adenocarcinoma may be attributable to shared genetic susceptibility loci.

  9. Altering the sex determination pathway in Drosophila fat body modifies sex-specific stress responses

    PubMed Central

    Neckameyer, Wendi S.

    2014-01-01

    The stress response in Drosophila melanogaster reveals sex differences in behavior, similar to what has been observed in mammals. However, unlike mammals, the sex determination pathway in Drosophila is well established, making this an ideal system to identify factors involved in the modulation of sex-specific responses to stress. In this study, we show that the Drosophila fat body, which has been shown to be important for energy homeostasis and sex determination, is a dynamic tissue that is altered in response to stress in a sex and time-dependent manner. We manipulated the sex determination pathway in the fat body via targeted expression of transformer and transformer-2 and analyzed these animals for changes in their response to stress. In the majority of cases, manipulation of transformer or transformer-2 was able to change the physiological output in response to starvation and oxidative stress to that of the opposite sex. Our data also uncover the possibility of additional downstream targets for transformer and transformer-2 that are separate from the sex determination pathway and can influence behavioral and physiological responses. PMID:24789992

  10. Addressing the Photometric Calibration Challenge: Explicit Determination of the Instrumental Response and Atmospheric Response Functions, and Tying it All Together.

    NASA Astrophysics Data System (ADS)

    Stubbs, C. W.; Tonry, J. L.

    2016-05-01

    Photometric calibration is currently the dominant source of systematic uncertainty in exploiting type Ia supernovae to determine the nature of the dark energy. We review our ongoing program to address this calibration challenge by performing measurements of both the instrumental response function and the optical transmission function of the atmosphere. A key aspect of this approach is to complement standard star observations by using NIST-calibrated photodiodes as a metrology foundation for optical flux measurements. We present our first attempt to assess photometric consistency between synthetic photometry and observations, by comparing predictions based on a NIST-diode-based determination of the PanSTARRS-1 instrumental response and empirical atmospheric transmission measurements, with fluxes we obtained from observing spectrophotometric standards.

  11. Determinants of Pain Treatment Response and Non-Response: Identification of TMD Patient Subgroups

    PubMed Central

    Litt, Mark D.; Porto, Felipe B.

    2013-01-01

    The purpose of the present study was to determine if we could identify a specific subtype of temporomandibular disorder (TMD) pain patients that does not respond to treatment. Patients were 101 men and women with chronic TMD pain recruited from the community and randomly assigned to one of two treatment conditions: a standard conservative care (STD) condition or a standard care plus cognitive-behavioral treatment condition (STD+CBT) in which patients received all elements of STD, but also received cognitive-behavioral coping skills training. Growth mixture modeling, incorporating a series of treatment-related predictors, was used to distinguish several distinct classes of responders or non-responders to treatment based on reported pain over a one-year follow-up period. Results indicated that treatment non-responders accounted for 16% of the sample, and did not differ from treatment responders on demographics or temporomandibular joint pathology, but that they reported more psychiatric symptoms, poorer coping, and higher levels of catastrophizing. Treatment-related predictors of membership in treatment responder groups versus the non-responder group included the addition of CBT to standard treatment, treatment attendance, and decreasing catastrophization. It was concluded that CBT may be made more efficacious for TMD patients by placing further emphasis on decreasing catastrophization and on individualizing care. PMID:24094979

  12. Identification of inhibitors of ovarian cancer stem-like cells by high-throughput screening

    PubMed Central

    2012-01-01

    Background Ovarian cancer stem cells are characterized by self-renewal capacity, ability to differentiate into distinct lineages, as well as higher invasiveness and resistance to many anticancer agents. Since they may be responsible for the recurrence of ovarian cancer after initial response to chemotherapy, development of new therapies targeting this special cellular subpopulation embedded within bulk ovarian cancers is warranted. Methods A high-throughput screening (HTS) campaign was performed with 825 compounds from the Mechanistic Set chemical library [Developmental Therapeutics Program (DTP)/National Cancer Institute (NCI)] against ovarian cancer stem-like cells (CSC) using a resazurin-based cell cytotoxicity assay. Identified sets of active compounds were projected onto self-organizing maps to identify their putative cellular response groups. Results From 793 screening compounds with evaluable data, 158 were found to have significant inhibitory effects on ovarian CSC. Computational analysis indicates that the majority of these compounds are associated with mitotic cellular responses. Conclusions Our HTS has uncovered a number of candidate compounds that may, after further testing, prove effective in targeting both ovarian CSC and their more differentiated progeny. PMID:23078816

  13. Comparing long term impact on ovarian reserve between laparoscopic ovarian cystectomy and open laprotomy for ovarian endometrioma

    PubMed Central

    2013-01-01

    Objective To compare the long term impact on ovarian reserve between laparoscopic ovarian cystectomy with bipolar electrocoagulation and laparotomic cystectomy with suturing for ovarian endometrotic cyst. Patient and method(s) 121 patients with benign ovarian endometroitic cysts were randomised to either laparoscopic ovarian cystectomy using bipolar electrocoagulation (61 patients) or laparotomic ovarian cystectomy using sutures (60 patients). Serum follicle-stimulating hormone, Antimullerian hormon, Basal antral follicle Count, mean ovarian diameter, and ovarian stromal blood flow velocity were measured at 6, 12 and 18 months after surgery and compared in both groups. Result(s) A statistically significant increase of serum FSH was found in the laproscopic bipolar group at 6-, 12 and 18-month postoperativly compared to open laparotomy suture group. Also, a statistically significant decrease of the mean AMH value occurred in laproscopic bipolar group at 6-, 12 and 18-month follow- up compared to open laparotomy suture group. Basal antral follicle number, mean ovarian diameter and peak systolic velocity were significantly decreased during the 6-, 12,18 -month follow-up in laproscopic bipolar group compared to open laparotomy suture group. Conclusion(s) After laproscopic ovarian cystecomy for endometrioma all pareameter of ovarian reseve are significantly decreased on long term follow up as compared to open laprotomy. PMID:24180348

  14. Study of ovarian cancer management.

    PubMed

    Gaughan, E; Javaid, T; Cooley, S; Byrne, P; Gaughan, G

    2006-10-01

    Ovarian cancer is the most lethal gynecological malignancy. Many patients present at an advanced stage as the symptoms of early stage disease can be vague. AIM We evaluated the demographics, treatment regimens and survival rates of ovarian cancer patients attending Beaumont Hospital Dublin over a nine year period. A retrospective chart review of ovarian cancer patients attending Beaumont Hospital between 11/10/94 and 30/6/3 was performed. Patients were selected from pathology records. Patients with borderline histology and those who died of unrelated causes were excluded. 31% of individuals presented with distension as their only clinical sign. 20% presented with a mass as their only clinical sign. The most common cell type was papillary serous adenocarcinoma in two thirds of cases. 54% presented with advanced disease [stage IIl-IV]. Treatment involved surgical clearance or debulking +/- chemotherapy. 5 year survival for Stage I was 95% versus 19% for Stage IlI. This highlights the importance of early diagnosis.

  15. Long noncoding RNA MALAT1-regulated microRNA 506 modulates ovarian cancer growth by targeting iASPP

    PubMed Central

    Lei, Ruilin; Xue, Min; Zhang, Lan; Lin, ZhongQiu

    2017-01-01

    MALAT1, an important cancer-associated long noncoding RNA (lncRNA), contributes to the development and progression of several cancers. Disordered expression of MALAT1 has been observed in several cancers, including cervical cancer, breast cancer, and ovarian cancer. However, the exact effects and molecular mechanisms of MALAT1 in ovarian cancer progression are still unknown. Here, we investigated the role of MALAT1 in human ovarian cancer cell lines and clinical tumor samples, in order to determine the function of this molecule. In our research, lncRNA-MALAT1 was specifically upregulated in ovarian cancer cell lines and promoted ovarian cancer-cell growth through targeting microRNA (miR)-506. Knockdown of MALAT1 inhibited the proliferation and DNA synthesis of human ovarian cancer cell in vitro. In addition, miR-506-dependent iASPP regulation was required in MALAT1-induced ovarian cancer-cell growth. These findings indicated that MALAT1 might suppress tumor growth via miR-506-dependent iASPP regulation. Taken together, our data indicated that MALAT1 might be an oncogenic lncRNA that promotes proliferation of ovarian cancer and could be regarded as a therapeutic target in human ovarian cancer. PMID:28031721

  16. Leukocyte-associated immunoglobulin-like receptor-1 expressed in epithelial ovarian cancer cells and involved in cell proliferation and invasion

    SciTech Connect

    Cao, Qizhi; Fu, Aili; Yang, Shude; He, Xiaoli; Wang, Yue; Zhang, Xiaoshu; Zhou, Jiadi; Luan, Xiying; Yu, Wenzheng; Xue, Jiangnan

    2015-03-06

    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.

  17. Comparative effectiveness of imaging modalities to determine metastatic breast cancer treatment response.

    PubMed

    Lee, Christoph I; Gold, Laura S; Nelson, Heidi D; Chou, Roger; Ramsey, Scott D; Sullivan, Sean D

    2015-02-01

    We performed a systematic review to address the comparative effectiveness of different imaging modalities in evaluating treatment response among metastatic breast cancer patients. We searched seven multidisciplinary electronic databases for relevant publications (January 2003-December 2013) and performed dual abstraction of details and results for all clinical studies that involved stage IV breast cancer patients and evaluated imaging for detecting treatment response. Among 159 citations reviewed, 17 single-institution, non-randomized, observational studies met our inclusion criteria. Several studies demonstrate that changes in PET/CT standard uptake values are associated with changes in tumor volume as determined by bone scan, MRI, and/or CT. However, no studies evaluated comparative test performance between modalities or determined relationships between imaging findings and subsequent clinical decisions. Evidence for imaging's effectiveness in determining treatment response among metastatic breast cancer patients is limited. More rigorous research is needed to address imaging's value in this patient population.

  18. Photoacoustic characterization of ovarian tissue

    NASA Astrophysics Data System (ADS)

    Aguirre, Andres; Gamelin, John; Guo, Puyun; Yan, Shikui; Sanders, Mary; Brewer, Molly; Zhu, Quing

    2009-02-01

    Ovarian cancer has the highest mortality of all gynecologic cancers with a five-year survival rate of only 30%. Because current imaging techniques (ultrasound, CT, MRI, PET) are not capable of detecting ovarian cancer early, most diagnoses occur in later stages (III/IV). Thus many women are not correctly diagnosed until the cancer becomes widely metastatic. On the other hand, while the majority of women with a detectable ultrasound abnormality do not harbor a cancer, they all undergo unnecessary oophorectomy. Hence, new imaging techniques that can provide functional and molecular contrasts are needed for improving the specificity of ovarian cancer detection and characterization. One such technique is photoacoustic imaging, which has great potential to reveal early tumor angiogenesis through intrinsic optical absorption contrast from hemoglobin or extrinsic contrast from conjugated agents binding to appropriate molecular receptors. To better understand the cancer disease process of ovarian tissue using photoacoustic imaging, it is necessary to first characterize the properties of normal ovarian tissue. We have imaged ex-vivo ovarian tissue using a 3D co-registered ultrasound and photoacoustic imaging system. The system is capable of volumetric imaging by means of electronic focusing. Detecting and visualizing small features from multiple viewing angles is possible without the need for any mechanical movement. The results show strong optical absorption from vasculature, especially highly vascularized corpora lutea, and low absorption from follicles. We will present correlation of photoacoustic images from animals with histology. Potential application of this technology would be the noninvasive imaging of the ovaries for screening or diagnostic purposes.

  19. Biomarkers of ovarian reserve as predictors of reproductive potential.

    PubMed

    Steiner, Anne Z

    2013-11-01

    The size of the oocyte pool, the ovarian reserve, can determine a woman's reproductive stage. Chronologic age, anti-Müllerian hormone (AMH) levels, early follicular phase follicle-stimulating hormone levels, and early follicular phase inhibin B levels are correlated with ovarian reserve. Therefore, these biomarkers of ovarian reserve should serve as predictors of reproductive potential. Clinical and epidemiologic studies suggest that historical and laboratory biomarkers of ovarian reserve are associated with natural and treatment-related fertility. However, controversy remains as to their ability to predict reproductive potential. For infertile women undergoing assisted reproductive technology treatment, these biomarkers tend to be highly specific but not sensitive for cycle failure (nonpregnancy). While these biomarkers are being used as "fertility tests" in the general population, their value as predictors of unassisted fertility is still uncertain. Among laboratory biomarkers, AMH appears to have the most promise; however, further studies are needed to refine cutoff values and to determine test characteristics in the prediction of natural fertility or infertility in the general population.

  20. The role of surgery in advanced epithelial ovarian cancer

    PubMed Central

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

    2016-01-01

    Nowadays, the standard management of advanced epithelial ovarian cancer is correct surgical staging and optimal tumour cytoreduction followed by platinum and taxane-based chemotherapy. Standard surgical staging consists of peritoneal washings, total hysterectomy, and bilateral salpingo-oophorectomy, inspection of all abdominal organs and the peritoneal surface, biopsies of suspicious areas or randomised biopsies if they are not present, omentectomy and para-aortic lymphadenectomy. After this complete surgical staging, the International Federation of Gynaecology and Obstetrics (FIGO) staging system for ovarian cancer is applied to determine the management and prognosis of the patient. Complete tumour cytoreduction has shown an improvement in survival. There are some criteria to predict cytoreduction outcomes based on serum biomarkers levels, preoperative imaging techniques, and laparoscopic-based scores. Optimised patient selection for primary cytoreduction would determine patients who could benefit from an optimal cytoreduction and might benefit from interval surgery. The administration of intraperitoneal chemotherapy after debulking surgery has shown an increase in progression-free survival and overall survival, especially in patients with no residual disease after surgery. It is considered that 3–17% of all epithelial ovarian carcinoma (EOC) occur in young women that have not fulfilled their reproductive desires. In these patients, fertility-sparing surgery is a worthy option in early ovarian cancer. PMID:27594911

  1. The Role of Fanconi/BRCA DNA Repair Pathway in Epithelial Ovarian Carcinogenesis

    DTIC Science & Technology

    2015-01-01

    linking agents, including cisplatin . In fact, increased chromosomal breakage in response to DNA cross-linkers (mitomycin C and diepoxybutane) is the...BRCA pathway in cisplatin -sensitive ovarian tumors. Nat Med 9, 568-574 (2003). 14 Wang, Z., Li, M., Lu, S., Zhang, Y. & Wang, H. Promoter...management of ovarian cancer. Ann Oncol, 22 Suppl 8, viii5. D’ANDREA, A.D. (2003). The Fanconi Anemia/BRCA signaling pathway: disruption in cisplatin

  2. Extracellular matrix composition determines astrocyte responses to mechanical and inflammatory stimuli.

    PubMed

    Johnson, Kasey M; Milner, Richard; Crocker, Stephen J

    2015-07-23

    Astrocytes perform critical homeostatic physiological functions in the central nervous system (CNS) and are robustly responsive to injury, inflammation, or infection. We hypothesized that the components of the extracellular matrix (ECM), which are known to vary during development and in response to disease, determine astrocytic responses to injury and inflammation. We examined the response of primary astrocyte cultures grown on different ECM proteins to a mechanical wound (i.e., scratch). ECM substrates selected were laminin (Ln), vitronectin (Vn), fibronectin (Fn) or Tenascin C (TnC). We found that regrowth of the scratch wound was ECM dependent: recovery was arrested on fibronectin (Fn), almost complete on either Vn, Ln, or TnC. To determine whether ECM responses were also influenced by inflammation, we treated ECM plated cultures with interleukin-1β (IL-1β). We found that IL-1β arrested astrocyte growth on Ln, accelerated astrocyte growth on Fn and had no significant effect on astrocyte growth on TnC or Vn. We also determined that blocking β1integrins, the major class of receptors for all ECM proteins tested, prevented the robust response of astrocytes exposed to TnC, Ln and Vn, and also inhibited the robust effect of IL-1β to stimulate astrocyte growth on Fn. In addition, we evaluated downstream targets of integrin signaling, specifically the mammalian target of rapamycin (mTOR), and determined that activation of this pathway contributed to the response of astrocytes grown on TnC, but not on Ln, Vn or Fn. These findings provide new insights into the role of ECM as a source of heterogeneity of glial responses that may have important implications for neuropathological sequelae.

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

    PubMed

    Khiewvan, Benjapa; Torigian, Drew A; Emamzadehfard, Sahra; Paydary, Koosha; Salavati, Ali; Houshmand, Sina; Werner, Thomas J; Alavi, Abass

    2017-02-08

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

  4. Ovarian metastases: Computed tomographic appearances

    SciTech Connect

    Megibow, A.J.; Hulnick, D.H.; Bosniak, M.A.; Balthazar, E.J.

    1985-07-01

    Computed tomographic scans of 34 patients with ovarian metastases were reviewed to assess the radiographic appearances and to correlate these with the primary neoplasms. Primary neoplasms were located in the colon (20 patients), breast (six), stomach (five), small bowel (one), bladder (one), and Wilms tumor of the kidney (one). The radiographic appearance of the metastatic lesions could be described as predominantly cystic (14 lesions), mixed (12 lesions), or solid (seven lesions). The cystic and mixed lesions tended to be larger in overall diameter than the solid. The metastases from gastric carcinoma appeared solid in four of five cases. The metastases from the other neoplasms had variable appearances simulating primary ovarian carcinoma.

  5. Ovarian response and embryo production in llamas treated with equine chorionic gonadotropin alone or with a progestin-releasing vaginal sponge at the time of follicular wave emergence.

    PubMed

    Huanca, W; Cordero, A; Huanca, T; Cardenas, O; Adams, G P; Ratto, M H

    2009-10-01

    The objective of the study was to compare the ovulatory response and embryo production in llamas (Lama glama) treated with a single dose of equine chorionic gonadotropin (eCG) alone or combined with intravaginal medroxyprogesterone acetate (MPA) at the time of follicular wave emergence. Llamas with a growing follicle >or=7 mm in diameter were assigned to one of the following groups: (1) Control (n=28): Nonstimulated llamas were mated and embryos were collected 7 d after mating. (2) eCG (n=32): Llamas were given 5mg luteinizing hormone (LH) (Day 0) to induce ovulation, 1000 IU eCG on Day 2, a luteolytic dose of prostaglandin F(2alpha) on Day 6, mating on Day 7, and embryo collection on Day 14. (3) eCG+MPA (n=34): Llamas were treated as those in the eCG group, but a sponge containing 60 mg MPA was placed intravaginally from Days 2 to 6. Llamas that did not respond to synchronization or superstimulation were excluded, leaving data from n=26, 26, and 27 in the control, eCG, and eCG+MPA groups, respectively, for statistical analysis. The mean (+/-SD) number of follicles>7 mm at the time of mating was greatest in the eCG group, intermediate in the eCG+MPA group, and lowest in the control group (16.6+/-5.3, 12.9+/-3.7, and 1.0+/-0.0, respectively, P<0.001). The number of corpora lutea was similar between eCG and eCG+MPA groups (10.1+/-2.9 and 8.6+/-3.7, respectively); both were higher (P<0.001) than in controls (0.9+/-0.3). The number of embryos did not differ significantly between the eCG and eCG+MPA groups (4.8+/-2.8 and 3.5+/-3.0, respectively), but both were higher (P<0.001) than in the controls (0.7+/-0.4). In conclusion, eCG, with or without MPA effectively induced a superovulatory response and multiple embryo production in llamas.

  6. [Neurobiological determinism: questionable inferences on human freedom of choice and forensic criminal responsibility].

    PubMed

    Urbaniok, F; Hardegger, J; Rossegger, A; Endrass, J

    2006-08-01

    Several authors argue that criminal behavior is generally caused by neurobiological deficits. Based on this neurobiological perspective of assumed causality, the concept of free will is questioned, and the theory of neurobiological determinism of all human behavior is put forward, thus maintaining that human beings are not responsible for their actions, and consequently the principle of guilt should be given up in criminal law. In this context the controversial debate on determinism and indeterminism, which has been held for centuries, has flared up anew, especially within the science of criminal law. When critically examining the current state of research, it becomes apparent that the results do not support the existence of a universally valid neurobiological causality of criminal behavior, nor a theory of an absolute neurobiological determinism. Neither is complete determination of all phenomena in the universe--as maintained--the logical conclusion of the principle of causality, nor is it empirically confirmed. Analyzed methodically, it cannot be falsified, and thus, as a theory which cannot be empirically tested, it represents a dogma against which plausible objections can be made. The criticism of the concept of free will, and even more so of human accountability and criminal responsibility, is not put forward in a valid way. The principle of relative determinism--the evaluation of the degree of determinism of personality factors potentially reducing criminal responsibility, which includes concrete observations and analysis of behavior--thus remains a central and cogent approach to the assessment of criminal responsibility. To sum up, the theories proposed by some authors on the complete neurobiological determinism of human behavior, and the subsequent impossibility of individual responsibility and guilt, reveal both methodical misconception and a lack of empirical foundation.

  7. Determination of continuous system transfer functions from sampled pulse response data

    NASA Astrophysics Data System (ADS)

    Jordan, Jay B.

    1993-09-01

    A method for determining the transfer function of a continuous system from sampled responses to single and multiple pulse excitation is presented. The method is an extension of the sampled edge response method pioneered by the theoretical work of A. Papoulis in 1962 and the application of the theory to optical systems by B. Tatian in 1965. Occasions arise when pulse rather than step function stimuli are available for system excitations. In such cases, the method presented is practical for determining the system transfer function. The use of anti- aliasing filters and estimation of non-bandwidth limited transfer functions are also discussed.

  8. Baroreflex sensitivity as a determinant of responses to hydralazine in dogs.

    PubMed

    Vidrio, H

    1983-01-01

    In order to evaluate the relation between hypotension induced by hydralazine and the resultant reflex tachycardia, as well as the role of baroreflex sensitivity in determining the magnitude of these responses, the drug was administered orally at a dose of 1 mg/kg to a group of trained conscious normotensive and renal hypertensive dogs. Responses were assessed by measuring blood pressure and heart rate for 8 hr after dosing and integrating the changes observed over time in order to obtain a mean value. Baroreflex gain was calculated as the ratio of heart rate to blood pressure responses. Hypotension was greater in hypertensives, whereas tachycardia was not different between groups. Gain was therefore smaller in hypertensives, but not uniformly so, a portion of these animals having values within the normotensive range. This high gain group responded with less hypotension and more tachycardia than did the low gain group. Differences in pressure and rate responses to repeated administration of hydralazine between the two groups were minimal. It is suggested that baroreflex gain, an innate individual characteristic, is an important determinant of acute pressure responses to hydralazine in dogs, hypertensive animals having less gain than normotensives and showing increased hypotensive responses. Gain appears not to be as important in determining the chronic effects of the drug.

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

    ClinicalTrials.gov

    2014-12-18

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

  10. Polycystic ovarian disease.

    PubMed

    Raj, S G; Talbert, L M

    1984-01-01

    Polycystic ovarian disease (PCOD) was first described as a single disease by Stein and Leventhal in 1935, but now has been separated into several distinct entities, comprising a symptom complex. The most frequent presenting symptoms associated with PCOD are obesity, hirsutism, amenorrhea or anovulation, dysfunctional uterine bleeding, irregular menses, and infertility. The common finding of hirsutism in PCOD patients is a reflection of the hyperandrogenism resulting from elevation of all the androgens, including testosterone, androstenediol, dehydroepiandrostrone sulfate (DHEA-S), and androstenedione. Some patients with all the clinical features of PCOD can be shown, through appropriate testing, to have an attenuated form of classic congenital adrenal hyperplasia (CAH). Serum follicle stimulating hormone (FSH) levels are usually low or in the normal range, and serum luteinizing hormone (LH) levels are usually elevated in patients with PCOD, resulting in an altered LH/FSH ratio. Treatment for PCOD must be based on the needs and desires of the individual patient, and on the pathophysiology of the patient's particular abnormalities. When pregnancy is desired, ovulation induction with clomiphene is indicated. Clomiphene is a weak estrogen that induces a transient rise in serum LH and FSH, followed by a gonadotropic pattern similar to normal cycles. A 72% ovulation rate and a 41.8% conception rate have been reported after treatment with clomiphene. In patients who do not respond to clomiphene, or clomiphene with added human chorionic gonadotropin (hCG), human menopausal gonadotropin (hMG) can be used to induce ovulation, but the patient should be closely monitored for multiple ovulation, multiple pregnancy, or hyperstimulation syndrome. For patients not interested in conception, regular menstrual cyclicity can be restored and hyperandrogenism reduced with oral contraceptives (OCs).

  11. Surgery for advanced epithelial ovarian cancer.

    PubMed

    Hacker, Neville F; Rao, Archana

    2016-10-20

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

  12. Targeting the tumour microenvironment in ovarian cancer.

    PubMed

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

    2016-03-01

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

  13. Application of several methods for determining transfer functions and frequency response of aircraft from flight data

    NASA Technical Reports Server (NTRS)

    Eggleston, John M; Mathews, Charles W

    1954-01-01

    In the process of analyzing the longitudinal frequency-response characteristics of aircraft, information on some of the methods of analysis has been obtained by the Langley Aeronautical Laboratory of the National Advisory Committee for Aeronautics. In the investigation of these methods, the practical applications and limitations were stressed. In general, the methods considered may be classed as: (1) analysis of sinusoidal response, (2) analysis of transient response as to harmonic content through determination of the Fourier integral by manual or machine methods, and (3) analysis of the transient through the use of least-squares solutions of the coefficients of an assumed equation for either the transient time response or frequency response (sometimes referred to as curve-fitting methods). (author)

  14. The Association Between Talc Use and Ovarian Cancer

    PubMed Central

    Vitonis, Allison F.; Terry, Kathryn L.; Welch, William R.; Titus, Linda J.

    2016-01-01

    Background: Multiple studies of ovarian cancer and genital talc use have led only to consensus about possible carcinogenicity. Seeking greater clarity, we examined this association in 2,041 cases with epithelial ovarian cancer and 2,100 age- and-residence-matched controls. Methods: We defined genital talc use as regular application to the genital/rectal area directly, on sanitary napkins, tampons, or underwear. To estimate “talc-years,” we multiplied applications per year by years used. Unconditional logistic regression, Wald statistics, likelihood-ratio tests, and polytomous logistic regression were used to calculate adjusted odds ratios (OR) and 95% confidence intervals (CI), trends, effect-modification, and heterogeneity by ovarian cancer histologic subtype. Results: Overall, genital talc use was associated with an OR (95% CI) of 1.33 (1.16, 1.52), with a trend for increasing risk by talc-years. Women who used talc were more likely to be older, heavier, asthma sufferers, and regular analgesic users—none of which was a confounder. Dose–responses were more apparent for premenopausal women, especially nonsmokers and those heavier or postmenopausal users of menopausal hormones (hormone therapy [HT]). Subtypes of ovarian cancer more likely to be associated with talc included invasive serous and endometrioid tumors and borderline serous and mucinous tumors. Premenopausal women and postmenopausal HT users with these subtypes who had accumulated >24 talc-years had ORs (95% CI) of 2.33 (1.32, 4.12) and 2.57 (1.51, 4.36), respectively. Conclusion: Risks for epithelial ovarian cancer from genital talc use vary by histologic subtype, menopausal status at diagnosis, HT use, weight, and smoking. These observations suggest that estrogen and/or prolactin may play a role via macrophage activity and inflammatory response to talc. PMID:26689397

  15. The thrombospondin-1 receptor CD36 is an important mediator of ovarian angiogenesis and folliculogenesis

    PubMed Central

    2014-01-01

    Background Ovarian angiogenesis is a complex process that is regulated by a balance between pro- and anti-angiogenic factors. Physiological processes within the ovary, such as folliculogenesis, ovulation, and luteal formation are dependent upon adequate vascularization and anything that disrupts normal angiogenic processes may result in ovarian dysfunction, and possibly infertility. The objective of this study was to evaluate the role of the thrombospondin-1 (TSP-1) receptor CD36 in mediating ovarian angiogenesis and regulating ovarian function. Methods The role of CD36 was evaluated in granulosa cells in vitro and ovarian morphology and protein expression were determined in wild type and CD36 null mice. Results In vitro, CD36 inhibition increased granulosa cell proliferation and decreased apoptosis. Granulosa cells in which CD36 was knocked down also exhibited an increase in expression of survival and angiogenic proteins. Ovaries from CD36 null mice were hypervascularized, with increased expression of pro-angiogenic vascular endothelial growth factor (VEGF) and its receptor VEGFR-2. Ovaries from CD36 null mice contained an increase in the numbers of pre-ovulatory follicles and decreased numbers of corpora lutea. CD36 null mice also had fewer number of offspring compared to wild type controls. Conclusions The results from this study demonstrate that CD36 is integral to the regulation of ovarian angiogenesis by TSP-1 and the expression of these family members may be useful in the control of ovarian vascular disorders. PMID:24628875

  16. Tumor-associated macrophages drive spheroid formation during early transcoelomic metastasis of ovarian cancer

    PubMed Central

    Yin, Mingzhu; Li, Xia; Tan, Shu; Zhou, Huanjiao Jenny; Ji, Weidong; Bellone, Stefania; Xu, Xiaocao; Zhang, Haifeng; Santin, Alessandro D.; Lou, Ge

    2016-01-01

    Tumor-associated macrophages (TAMs) can influence ovarian cancer growth, migration, and metastasis, but the detailed mechanisms underlying ovarian cancer metastasis remain unclear. Here, we have shown a strong correlation between TAM-associated spheroids and the clinical pathology of ovarian cancer. Further, we have determined that TAMs promote spheroid formation and tumor growth at early stages of transcoelomic metastasis in an established mouse model for epithelial ovarian cancer. M2 macrophage–like TAMs were localized in the center of spheroids and secreted EGF, which upregulated αMβ2 integrin on TAMs and ICAM-1 on tumor cells to promote association between tumor cells and TAM. Moreover, EGF secreted by TAMs activated EGFR on tumor cells, which in turn upregulated VEGF/VEGFR signaling in surrounding tumor cells to support tumor cell proliferation and migration. Pharmacological blockade of EGFR or antibody neutralization of ICAM-1 in TAMs blunted spheroid formation and ovarian cancer progression in mouse models. These findings suggest that EGF secreted from TAMs plays a critical role in promoting early transcoelomic metastasis of ovarian cancer. As transcoelomic metastasis is also associated with many other cancers, such as pancreatic and colon cancers, our findings uncover a mechanism for TAM-mediated spheroid formation and provide a potential target for the treatment of ovarian cancer and other transcoelomic metastatic cancers. PMID:27721235

  17. Hyperosmotic stress induces cisplatin sensitivity in ovarian cancer cells by stimulating aquaporin-5 expression

    PubMed Central

    CHEN, XUEJUN; ZHOU, CHUNXIA; YAN, CHUNXIAO; MA, JIONG; ZHENG, WEI

    2015-01-01

    Aquaporins (AQPs) are important mediators of water permeability and are closely associated with tumor cell proliferation, migration, angiogenesis and chemoresistance. Moreover, the chemosensitivity of tumor cells to cisplatin (CDDP) is potentially affected by osmotic pressure. The present study was undertaken to determine whether hyperosmosis regulates ovarian cancer cell sensitivity to CDDP in vitro and to explore whether this is associated with AQP expression. The hyperosmotic stress was induced by D-sorbitol. 3AO ovarian cancer cells were treated with different concentrations of hypertonic medium and/or CDDP for various times, followed by measuring the inhibition rate of cell proliferation using an MTT assay. In addition, AQP expression in response to osmotic pressure and/or CDDP was measured by reverse transcription-quantitative polymerase chain reaction and western blotting. Cell proliferation in response to hypertonic stress was also measured when AQP5 was knocked down by small interfering (si)RNA. 3AO cell proliferation was inhibited by hyperosmotic stress, while the expression of AQP5, but not that of AQP1, AQP3 or AQP9, was increased in a dose- and time-dependent manner in hypertonic sorbitol-containing medium. When AQP5 was silenced by siRNA, cells were susceptible to hypertonic stress. MTT analyses showed that the inhibition of cell proliferation by a low dose of CDDP increased significantly with exposure to a hyperosmotic stimulus, and this effect was reduced when a high dose of CDDP was used. AQP5 expression was induced by a low dose of CDDP, but was reduced by a high dose of CDDP. However, hyperosmosis enhanced AQP5 mRNA expression at every dose of CDDP tested, compared with isotonic medium. With prolonged treatment time, AQP5 expression was reduced by CDDP in hypertonic and isotonic culture medium. Thus, the effects of hyperosmosis on cell sensitivity to CDDP were associated with AQP5 expression. These results suggest that AQP5 expression in ovarian

  18. Differential effects of rapalogues, dual kinase inhibitors on human ovarian carcinoma cells in vitro.

    PubMed

    Rogers-Broadway, Karly-Rai; Chudasama, Dimple; Pados, George; Tsolakidis, Dimitris; Goumenou, Anastasia; Hall, Marcia; Karteris, Emmanouil

    2016-07-01

    Ovarian cancer is the second most common gynaecological malignancy and was diagnosed in over 7,000 women in 2011 in the UK. There are currently no reliable biomarkers available for use in a regular screening assay for ovarian cancer and due to characteristic late presentation (78% in stages III and IV) ovarian cancer has a low survival rate (35% after 10 years). The mTOR pathway is a central regulator of growth, proliferation, apoptosis and angiogenesis; providing balance between available resources such as amino acids and growth factors, and stresses such as hypoxia, to control cellular behaviour accordingly. Emerging data links mTOR with the aetiopathogenesis of ovarian cancer. We hypothesised that mTOR inhibitors could play a therapeutic role in ovarian cancer treatment. In this study we began by validating the expression of four main mTOR pathway components, mTOR, DEPTOR, rictor and raptor, at gene and protein level in in vitro models of endometrioid (MDAH‑2774) and clear cell (SKOV3) ovarian cancer using qPCR and ImageStream technology. Using a wound healing assay we show that inhibition of the mTOR pathway using rapamycin, rapalogues, resveratrol and NVP BEZ-235 induces a cytostatic and not cytotoxic response up to 18 h in these cell lines. We extended these findings up to 72 h with a proliferation assay and show that the effects of inhibition of the mTOR pathway are primarily mediated by the dephosphorylation of p70S6 kinase. We show that mTOR inhibition does not involve alteration of mTOR pathway components or induce caspase 9 cleavage. Preclinical studies including ovarian tissue of ovarian cancer patients, unaffected controls and patients with unrelated gynaecological conditions show that DEPTOR is reliably upregulated in ovarian cancer.

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

    PubMed

    Stany, Michael P; Vathipadiekal, Vinod; Ozbun, Laurent; Stone, Rebecca L; Mok, Samuel C; Xue, Hui; Kagami, Takashi; Wang, Yuwei; McAlpine, Jessica N; Bowtell, David; Gout, Peter W; Miller, Dianne M; Gilks, C Blake; Huntsman, David G; Ellard, Susan L; Wang, Yu-Zhuo; Vivas-Mejia, Pablo; Lopez-Berestein, Gabriel; Sood, Anil K; Birrer, Michael J

    2011-01-01

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

  20. Autonomy of the epithelial phenotype in human ovarian surface epithelium: changes with neoplastic progression and with a family history of ovarian cancer.

    PubMed

    Dyck, H G; Hamilton, T C; Godwin, A K; Lynch, H T; Maines-Bandiera, S; Auersperg, N

    1996-12-20

    Epithelial ovarian carcinomas originate in the ovarian surface epithelium (OSE). In culture, OSE undergoes epithelio-mesenchymal conversion, an event mimicking a wound response, while ovarian carcinomas retain complex epithelial characteristics. To define the onset of this increased epithelial autonomy in ovarian neoplastic progression, we examined mesenchymal conversion in OSE from 25 women with no family histories (NFH-OSE) and 13 women with family histories (FH-OSE) of breast/ovarian cancer (including 8 with mutated BRCA1 or 17q linkage) and in 8 ovarian cancer lines. After 3-6 passages in monolayer culture, most NFH-OSE exhibited reduced keratin expression and high collagen type III expression. In contrast, keratin remained high but collagen expression was lower in p. 3-6 FH-OSE. This difference was lost in SV40-transformed lines, which all resembled FH-OSE. Most carcinoma lines remained epithelial and did not undergo mesenchymal conversion. In 3-dimensional (3-D) sponge culture, NFH-OSE cells dispersed and secreted abundant extracellular matrix (ECM). FH-OSE remained epithelial and did not secrete ECM. ECM production was also reduced in SV40-transformed lines. Carcinoma lines in 3-D formed epithelial cysts, aggregates and papillae and lacked ECM. Sponge contraction (a mesenchymal characteristic) was greater in NFH-OSE than in FH-OSE both before and after SV40 transformation and was absent in the cancer lines. Our results suggest that increased autonomy of epithelial characteristics is an early indicator of ovarian neoplastic progression and that phenotypic changes indicative of such autonomy are found already in overtly normal OSE from women with histories of familial breast/ovarian cancer.

  1. Expression of Leukocyte Inhibitory Immunoglobulin-like Transcript 3 Receptors by Ovarian Tumors in Laying Hen Model of Spontaneous Ovarian Cancer.

    PubMed

    Khan, Mohammad Faisal; Bahr, Janice M; Yellapa, Aparna; Bitterman, Pincas; Abramowicz, Jacques S; Edassery, Seby L; Basu, Sanjib; Rotmensch, Jacob; Barua, Animesh

    2012-04-01

    Attempts to enhance a patient's immune response and ameliorate the poor prognosis of ovarian cancer (OVCA) have largely been unsuccessful owing to the suppressive tumor microenvironment. Leukocyte immunoglobulin-like transcript 3 (ILT3) inhibitory receptors have been implicated in immunosuppression in several malignancies. The expression and role of ILT3 in the progression of ovarian tumors are unknown. This study examined the expression and association of ILT3 in ovarian tumors in laying hens, a spontaneous preclinical model of human OVCA. White Leghorn laying hens were selected by transvaginal ultrasound scanning. Serum and normal ovaries or ovarian tumors were collected. The presence of tumors and the expression of ILT3 were examined by routine histology, immunohistochemistry, Western blot analysis, and reverse transcription-polymerase chain reaction. In addition to stromal immune cell-like cells, the epithelium of the ovarian tumors also expressed ILT3 with significantly high intensity than normal ovaries. Among different subtypes of ovarian carcinomas, serous OVCA showed the highest ILT3 staining intensity, whereas endometrioid OVCA had the lowest intensity. Similar to humans, an immunoreactive protein band of approximately 55 kDa for ILT3 was detected in the ovarian tumors in hens. The patterns of ILT3 protein and messenger RNA expression by ovarian tumors in different subtypes and stages were similar to those of immunohistochemical staining. The results of this study suggest that laying hens may be useful to generate information on ILT3-associated immunosuppression in OVCA. This animal model also offers the opportunity to develop and test anti-ILT3 immunotherapy to enhance antitumor immunity against OVCA in humans.

  2. Application of Nanotechnology in the Targeted Release of Anticancer Drugs in Ovarian Cancer Treatment

    DTIC Science & Technology

    2006-12-01

    performed on the mice. Iron oxide particle in the size range of MagNaGels are known as Ultrasmall Super - Paramagnetic Iron Oxide (USPIO) particles and...localize the MagNaGel nanoparticles in an orthotopic ovarian cancer mouse model by MRI, mice were Injected intraperitoneally with ovarian cancer cells...Organs were harvested and drug levels determined. Relative nanoparticle distribution by MRI images were correlated with drug levels. 15

  3. Impact of the putative cancer stem cell markers and growth factor receptor expression on the sensitivity of ovarian cancer cells to treatment with various forms of small molecule tyrosine kinase inhibitors and cytotoxic drugs

    PubMed Central

    Puvanenthiran, Soozana; Essapen, Sharadah; Seddon, Alan M.; Modjtahedi, Helmout

    2016-01-01

    Increased expression and activation of human epidermal growth factor receptor (EGFR) and HER-2 have been reported in numerous cancers. The aim of this study was to determine the sensitivity of a large panel of human ovarian cancer cell lines (OCCLs) to treatment with various forms of small molecule tyrosine kinase inhibitors (TKIs) and cytotoxic drugs. The aim was to see if there was any association between the protein expression of various biomarkers including three putative ovarian cancer stem cell (CSC) markers (CD24, CD44, CD117/c-Kit), P-glycoprotein (P-gp), and HER family members and response to treatment with these agents. The sensitivity of 10 ovarian tumour cell lines to the treatment with various forms of HER TKIs (gefitinib, erlotinib, lapatinib, sapitinib, afatinib, canertinib, neratinib), as well as other TKIs (dasatinib, imatinib, NVP-AEW541, crizotinib) and cytotoxic agents (paclitaxel, cisplatin and doxorubicin), as single agents or in combination, was determined by SRB assay. The effect on these agents on the cell cycle distribution, and downstream signaling molecules and tumour migration were determined using flow cytometry, western blotting, and the IncuCyte Clear View cell migration assay respectively. Of the HER inhibitors, the irreversible pan-TKIs (canertinib, neratinib and afatinib) were the most effective TKIs for inhibiting the growth of all ovarian cancer cells, and for blocking the phosphorylation of EGFR, HER-2, AKT and MAPK in SKOV3 cells. Interestingly, while the majority of cancer cells were highly sensitive to treatment with dasatinib, they were relatively resistant to treatment with imatinib (i.e., IC50 >10 μM). Of the cytotoxic agents, paclitaxel was the most effective for inhibiting the growth of OCCLs, and of various combinations of these drugs, only treatment with a combination of NVP-AEW541 and paclitaxel produced a synergistic or additive anti-proliferative effect in all three cell lines examined (i.e., SKOV3, Caov3, ES2

  4. 48 CFR 53.301-308 - Standard Form 308, Request for Determination and Response to Request.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Standard Form 308, Request for Determination and Response to Request. 53.301-308 Section 53.301-308 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION (CONTINUED) CLAUSES AND FORMS FORMS Illustrations of...

  5. 48 CFR 53.301-308 - Standard Form 308, Request for Determination and Response to Request.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 2 2011-10-01 2011-10-01 false Standard Form 308, Request for Determination and Response to Request. 53.301-308 Section 53.301-308 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION (CONTINUED) CLAUSES AND FORMS FORMS Illustrations of...

  6. 48 CFR 53.301-308 - Request For wage Determination and Response to Request.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 2 2014-10-01 2014-10-01 false Request For wage Determination and Response to Request. 53.301-308 Section 53.301-308 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION (CONTINUED) CLAUSES AND FORMS FORMS Illustrations of Forms...

  7. 48 CFR 53.301-308 - Standard Form 308, Request for Determination and Response to Request.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 2 2013-10-01 2013-10-01 false Standard Form 308, Request for Determination and Response to Request. 53.301-308 Section 53.301-308 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION (CONTINUED) CLAUSES AND FORMS FORMS Illustrations of...

  8. Determining adaptive and adverse oxidative stress responses in human bronical epithelial cells exposed to zinc

    EPA Science Inventory

    Determining adaptive and adverse oxidative stress responses in human bronchial epithelial cells exposed to zincJenna M. Currier1,2, Wan-Yun Cheng1, Rory Conolly1, Brian N. Chorley1Zinc is a ubiquitous contaminant of ambient air that presents an oxidant challenge to the human lung...

  9. 12 CFR 652.75 - Your responsibility for determining the risk-based capital level.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Your responsibility for determining the risk-based capital level. 652.75 Section 652.75 Banks and Banking FARM CREDIT ADMINISTRATION FARM CREDIT SYSTEM FEDERAL AGRICULTURAL MORTGAGE CORPORATION FUNDING AND FISCAL AFFAIRS Risk-Based...

  10. On Values, Determinants of Spending, and Civil Rights: Response to Commentaries on Braddock et al.

    ERIC Educational Resources Information Center

    Braddock, David

    1987-01-01

    In response to comments on his nationwide study of public mental retardation/developmental disabilities spending in the states, the author considers classification of funds (income maintenance, large private facilities and prisons, nursing homes, and education/vocational rehabilitation), values, determinants, civil rights, and reform. (DB)

  11. 40 CFR 142.11 - Initial determination of primary enforcement responsibility.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... alternate drinking water supplies that is part of a State's Wellhead Protection Program, where such program... 40 Protection of Environment 24 2012-07-01 2012-07-01 false Initial determination of primary enforcement responsibility. 142.11 Section 142.11 Protection of Environment ENVIRONMENTAL PROTECTION...

  12. 40 CFR 142.11 - Initial determination of primary enforcement responsibility.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... alternate drinking water supplies that is part of a State's Wellhead Protection Program, where such program... 40 Protection of Environment 24 2013-07-01 2013-07-01 false Initial determination of primary enforcement responsibility. 142.11 Section 142.11 Protection of Environment ENVIRONMENTAL PROTECTION...

  13. 40 CFR 142.11 - Initial determination of primary enforcement responsibility.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... alternate drinking water supplies that is part of a State's Wellhead Protection Program, where such program... 40 Protection of Environment 23 2014-07-01 2014-07-01 false Initial determination of primary enforcement responsibility. 142.11 Section 142.11 Protection of Environment ENVIRONMENTAL PROTECTION...

  14. Analysis of Reward Functions in Learning: Unconscious Information Processing: Noncognitive Determinants of Response Strength

    DTIC Science & Technology

    1984-05-01

    Research Note 84-76 ANALYSIS OF REWARD FUNCTIONS IN LEARNING: UNCONSCIOUS INFORMATION PROCESSING : Lf NONCOGNITIVE DETERMINANTS OF RESPONSE STRENGTH...Melvin H. Marx University of Missouri, Columbia David W. Bessemer , Contracting Officer’s Representative0 Submitted by Robert M. Sasmor, Director BASIC...REPORT & PERIOD COVERED ANALYSIS OF REWARD FUNCTIONS IN LEARNING: Final Report UNCONSCIOUS INFORMATION PROCESSING : NONCOGNITIVE Sept. 1978 - Sept. 15

  15. 32 CFR 37.575 - What are my responsibilities for determining milestone payment amounts?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 1 2010-07-01 2010-07-01 false What are my responsibilities for determining milestone payment amounts? 37.575 Section 37.575 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DoD GRANT AND AGREEMENT REGULATIONS TECHNOLOGY INVESTMENT AGREEMENTS Pre-Award...

  16. 32 CFR 37.510 - What are my responsibilities for determining that a recipient is qualified?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 1 2010-07-01 2010-07-01 false What are my responsibilities for determining that a recipient is qualified? 37.510 Section 37.510 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DoD GRANT AND AGREEMENT REGULATIONS TECHNOLOGY INVESTMENT AGREEMENTS...

  17. 20 CFR 416.1014 - Responsibilities for obtaining evidence to make disability determinations.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 2 2012-04-01 2012-04-01 false Responsibilities for obtaining evidence to make disability determinations. 416.1014 Section 416.1014 Employees' Benefits SOCIAL SECURITY... those classes of cases described in the written guidelines for which the State agency does not make...

  18. 20 CFR 416.1014 - Responsibilities for obtaining evidence to make disability determinations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Responsibilities for obtaining evidence to make disability determinations. 416.1014 Section 416.1014 Employees' Benefits SOCIAL SECURITY... those classes of cases described in the written guidelines for which the State agency does not make...

  19. 20 CFR 416.1014 - Responsibilities for obtaining evidence to make disability determinations.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 2 2014-04-01 2014-04-01 false Responsibilities for obtaining evidence to make disability determinations. 416.1014 Section 416.1014 Employees' Benefits SOCIAL SECURITY... those classes of cases described in the written guidelines for which the State agency does not make...

  20. 20 CFR 416.1014 - Responsibilities for obtaining evidence to make disability determinations.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 2 2013-04-01 2013-04-01 false Responsibilities for obtaining evidence to make disability determinations. 416.1014 Section 416.1014 Employees' Benefits SOCIAL SECURITY... those classes of cases described in the written guidelines for which the State agency does not make...

  1. 21 CFR 111.73 - What is your responsibility for determining whether established specifications are met?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false What is your responsibility for determining whether established specifications are met? 111.73 Section 111.73 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION CURRENT...

  2. Response to Intervention: Considerations for School Leaders Concerning Specific Learning Disability Determination

    ERIC Educational Resources Information Center

    Robidas, Marian T.

    2013-01-01

    With the changes made to the Individuals with Disabilities Education Act of 2004 (Public Law 108-446), educational leadership is now able to use the Response to Intervention (RtI) process for Specific Learning Disability (SLD) determination rather than the long-standing discrepancy model (Individuals with Disabilities Education Act of 2004).…

  3. 32 CFR 37.510 - What are my responsibilities for determining that a recipient is qualified?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 1 2012-07-01 2012-07-01 false What are my responsibilities for determining that a recipient is qualified? 37.510 Section 37.510 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DoD GRANT AND AGREEMENT REGULATIONS TECHNOLOGY INVESTMENT AGREEMENTS...

  4. 32 CFR 37.510 - What are my responsibilities for determining that a recipient is qualified?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 1 2014-07-01 2014-07-01 false What are my responsibilities for determining that a recipient is qualified? 37.510 Section 37.510 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DoD GRANT AND AGREEMENT REGULATIONS TECHNOLOGY INVESTMENT AGREEMENTS...

  5. 32 CFR 37.510 - What are my responsibilities for determining that a recipient is qualified?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 1 2011-07-01 2011-07-01 false What are my responsibilities for determining that a recipient is qualified? 37.510 Section 37.510 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DoD GRANT AND AGREEMENT REGULATIONS TECHNOLOGY INVESTMENT AGREEMENTS...

  6. 32 CFR 37.510 - What are my responsibilities for determining that a recipient is qualified?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 1 2013-07-01 2013-07-01 false What are my responsibilities for determining that a recipient is qualified? 37.510 Section 37.510 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DoD GRANT AND AGREEMENT REGULATIONS TECHNOLOGY INVESTMENT AGREEMENTS...

  7. 32 CFR 37.575 - What are my responsibilities for determining milestone payment amounts?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 1 2012-07-01 2012-07-01 false What are my responsibilities for determining milestone payment amounts? 37.575 Section 37.575 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DoD GRANT AND AGREEMENT REGULATIONS TECHNOLOGY INVESTMENT AGREEMENTS Pre-Award...

  8. Ovarian Cancer Risk Prediction Models

    Cancer.gov

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

  9. Genetics Home Reference: ovarian cancer

    MedlinePlus

    ... a small or moderate contribution to overall ovarian cancer risk. Some of these genes provide instructions for making proteins that interact with the proteins produced from the BRCA1 or BRCA2 genes. Others act through different pathways. Researchers suspect that the combined influence of variations ...

  10. Immunohistochemical markers of cell cycle control applied to ovarian and primary peritoneal surface epithelial neoplasms: p21(WAF1/CIP1) predicts survival and good response to platinin-based chemotherapy.

    PubMed

    Costa, M J; Hansen, C L; Walls, J E; Scudder, S A

    1999-06-01

    Immunohistochemistry for p53, p21(WAF1/CIP1), and Ki-67 provides insight into the molecular events controlling the cell cycle. We tested the hypothesis that these cell cycle markers will aid in the clinical evaluation of ovarian and primary peritoneal surface epithelial neoplasms (SENs). Paraffin sections from a retrospective surgical series of 117 SENs were immunostained with anti-p53 (clone DO7, Novacastra Laboratories, UK), anti-p21(WAF1/CIP1) (clone EA10, Oncogene Science, Cambridge, MA), and anti-Ki-67 (clone MIB-1, Immunotech, Westbrook, ME). The Ki-67 proliferation index (Ki-67PI) and immunoreactivity were evaluated. One hundred seventeen SENs reacted as follows: p53 50%+ and p21(WAF1/CIP1) 65%+. Ki-67PI ranged from 4% to 88% (mean/median = 44/46%). p53 reactivity associated with transitional cell histology, decreased p21(WAF1/CIP1) staining, increased Ki-67PI, architectural/nuclear grade, and stage (P < .05, 1 x 10(-7), .01, .05/.0001, .001,). p21(WAF1/CIP1) staining was associated with endometrioid/clear cell histology, decreased Ki-67PI, architectural/nuclear grade, and stage (P < 05/.05, .05, .01/1 x 10(-8), 1 x 10(-5)). Ki-67PI associated with increased architectural/nuclear grade but not mucinous histology (P < 1 x 10(-5)/1 x 10(-6), .01). Sixty-seven patients had disease at last follow-up; 53 were dead of disease at 0 to 67 months (mean/median, 21/18), and 14 were alive with disease at 12 to 224 months (mean/median, 56/40). Fifty patients were disease free at 5 to 214 months (mean/median, 59/41). Predictors of survival include decreased Ki-67PI, stage, architectural/nuclear grade (P < 1 x 10(-6), 1 x 10(-10), 1 x 10(-10)/.005) and p21(WAF1/CIP1) IMS (multivariate P < 1 x 10(-6)). p21(WAF1/CIP1), a potent inhibitor of cyclin-dependent kinases necessary for cell cycle progression, functions as a key checkpoint in cell cycle control. Immunoreactivity for p21(WAF1/CIP1) provides prognostic information independent of other histological and clinical

  11. Determining the continuous family of quantum Fisher information from linear-response theory

    NASA Astrophysics Data System (ADS)

    Shitara, Tomohiro; Ueda, Masahito

    2016-12-01

    The quantum Fisher information represents a continuous family of metrics on the space of quantum states and places the fundamental limit on the accuracy of quantum state estimation. We show that the entire family of quantum Fisher information can be determined from linear-response theory through generalized covariances. We derive the generalized fluctuation-dissipation theorem that relates linear-response functions to generalized covariances and hence allows us to determine the quantum Fisher information from linear-response functions, which are experimentally measurable quantities. As an application, we examine the skew information, which is a quantum Fisher information, of a harmonic oscillator in thermal equilibrium, and show that the equality of the skew-information-based uncertainty relation holds.

  12. Detection of antibodies to ovarian antigens in women with premature ovarian failure.

    PubMed Central

    Wheatcroft, N J; Toogood, A A; Li, T C; Cooke, I D; Weetman, A P

    1994-01-01

    Premature ovarian failure is a common condition of uncertain aetiology in most cases, although autoimmunity is thought to play a role in a proportion of cases. The frequency of ovarian antibodies, which may be markers for an autoimmune aetiology in this condition, remains unclear. To define this further, we have examined the sera of 45 women with premature ovarian failure (five with iatrogenic ovarian failure, nine with an associated autoimmune disease, and 27 with idiopathic ovarian failure), as well as four women with infertility due to Turner's syndrome and 41 pre- and post-menopausal controls. Using two human ovarian antigen preparations, 24% and 60% of the ovarian failure patients reacted in an ELISA (P < 0.05 and P < 0.001 compared with controls), but frequent cross-reactivity was found with fallopian tube antigens. The apparent aetiology of ovarian failure did not correlate with the presence of ovarian antibodies. Using bovine ovary as an antigen, there was a significant overall increase in binding by the ovarian failure patients, but this was almost identical to binding in an ELISA with bovine fallopian tube. In contrast to a previous report, there was no significant increase of binding to soluble or Triton-extracted membrane fractions of bovine corpora lutea containing the LH/hCG receptor by the patients with ovarian failure. These results suggest that ovarian antibodies are common in premature ovarian failure, but their specificity and pathogenic role are questionable. PMID:8149656

  13. Determinants and short-term physiological consequences of PHA immune response in lesser kestrel nestlings.

    PubMed

    Rodríguez, Airam; Broggi, Juli; Alcaide, Miguel; Negro, Juan José; Figuerola, Jordi

    2014-08-01

    Individual immune responses are likely affected by genetic, physiological, and environmental determinants. We studied the determinants and short-term consequences of Phytohaemagglutinin (PHA) induced immune response, a commonly used immune challenge eliciting both innate and acquired immunity, on lesser kestrel (Falco naumanni) nestlings in semi-captivity conditions and with a homogeneous diet composition. We conducted a repeated measures analyses of a set of blood parameters (carotenoids, triglycerides, β-hydroxybutyrate, cholesterol, uric acid, urea, total proteins, and total antioxidant capacity), metabolic (resting metabolic rate), genotypic (MHC class II B heterozygosity), and biometric (body mass) variables. PHA challenge did not affect the studied physiological parameters on a short-term basis (<12 hr), except plasma concentrations of triglycerides and carotenoids, which decreased and increased, respectively. Uric acid was the only physiological parameter correlated with the PHA induced immune response (skin swelling), but the change of body mass, cholesterol, total antioxidant capacity, and triglycerides between sessions (i.e., post-pre treatment) were also positively correlated to PHA response. No relationships were detected between MHC gene heterozygosity or resting metabolic rate and PHA response. Our results indicate that PHA response in lesser kestrel nestlings growing in optimal conditions does not imply a severe energetic cost 12 hr after challenge, but is condition-dependent as a rapid mobilization of carotenoids and decrease of triglycerides is elicited on a short-term basis.

  14. A huge ovarian cyst in a hysterectomized bitch.

    PubMed

    Sontas, B H; Milani, C; Romagnoli, S; Bertolini, G; Caldin, M; Caliari, D; Zappulli, V; Mollo, A

    2011-12-01

    A 11-year-old, spayed, female mixed breed-dog was presented with an abdominal mass that was detected 1 month ago. Upon abdominal palpation a large, firm, oval shaped, movable mass was found in the mid-abdominal region. Survey radiograph of the abdomen demonstrated an oval soft tissue dense mass located on the right side of the abdominal cavity. A large, heteregenous and cystic mass with solid components occupying the majority of the abdomen and a small, cystic mass with solid components caudal to the left kidney were identified by transabdominal ultrasonography. Computed tomography scans revealed bilateral ovarian masses, and a small volume of retroperitoneal fluid on the right side. A cystic, but otherwise solid mass located in the right ovary and small retained left ovary encapsulated in the ovarian bursa were excised surgically by midline laparotomy. Histopathological examination of the excised mass from the right side revealed a large cystic structure consistent with an ovarian cyst and multiple corpora lutea and follicles at different maturational stages were detected in the left ovary. The precise origin of the ovarian cyst could not be determined by morphological appearance. Immunohistochemical staining suggested a cyst of surface epithelial origin. At re-examination 6 months after the surgery, the bitch appeared healthy and the clinical findings were all normal. To our knowledge, the cyst described here is the largest reported in an incompletely ovariohysterectomized bitch.

  15. Irisin immunostaining characteristics of breast and ovarian cancer cells.

    PubMed

    Kuloglu, T; Celik, O; Aydin, S; Hanifi Ozercan, I; Acet, M; Aydin, Y; Artas, G; Turk, A; Yardim, M; Ozan, G; Hanifi Yalcin, M; Kocaman, N

    2016-07-31

    To determine expression pattern of irisin in tissues obtained from human ovarian cancer, breast cancer, and cervix cancer. Tissue samples obtained from subjects with breast cancer, ovarian cancer cervix cancer, simple endometrial hyperplasia, complex atypical endometrial hyperplasia. At least five sections from each subject were immunohistochemically stained with irisin antibody, and H-score method was used to evaluate irisin intensity. Tissues obtained from healthy breast tissues, proliferative phase endometrium adenomyosis and benign ovarian tumors were accepted as control. Irisin activity was not detected in control breast tissues significantly increased irisin staining was detected in invasive lobular, intraductal papillary, invasive ductal, invasive papillary, and mucinous carcinomas compared to control tissues. Also, significantly increased irisin immunoreactivity was detected in both ovarian endometriosis and mucinous carcinomas compared to benign tumors. However irisin staining was not observed at the papillary carcinoma of the ovary while sections obtained from simple and complex atypical endometrial hyperplasia, and cervix carcinoma demonstrated irisin immunoreactivity. Increased irisin immunoreactivity in tissues obtained from breast, ovary, cervix carcinomas, and endometrial hyperplasia suggest critical role of this peptide during carcinogenesis.

  16. Heterotopic autotransplantation of ovarian cortex in cynomolgus monkeys.

    PubMed

    Igarashi, Suguru; Suzuki, Nao; Hashimoto, Shu; Takae, Seido; Takenoshita, Makoto; Hosoi, Yoshihiko; Morimoto, Yoshiharu; Ishizuka, Bunpei

    2010-02-01

    Abstract In recent years, removal of ova or ovaries before chemotherapy or radiation therapy has been investigated in young female cancer patients to avoid the adverse effects of treatment. Orthotopic autotransplantation of ovarian cortex has advantages such as easy collection of ova and the possibility of spontaneous pregnancy. Although children have been born after successful orthotopic autotransplantation into the residual ovaries, some patients cannot undergo this procedure such as those who need bilateral ovariectomy or pelvic radiation therapy, therefore it is still necessary to investigate suitable heterotopic autotransplantation sites. The present study was performed in primates (cynomolgus monkeys) with the objective of determining the optimum site for heterotopic autotransplantation of ovarian cortex to enhance the clinical application of this method. The retroperitoneal iliac fossa and omentum were selected as sites for heterotopic autotransplantation. Two cynomolgus monkeys were subjected to laparotomy under anesthesia. After resection of the bilateral adnexae, the ovaries were cut into 0.5 cm cubes that were transplanted. Blood levels of follicle-stimulating hormone, luteinizing hormone, estradiol, and progesterone were monitored, and monkeys with a regular estrus cycle underwent superovulation and egg collection. In both monkeys studied, recovery of a regular estrus cycle was confirmed after heterotopic autotransplantation of ovarian tissue. MII phase ova were successfully collected from tissues transplanted into the retroperitoneal iliac fossa or omentum. Development to the early blastocyst stage was confirmed after microfertilization. We established an appropriate method of heterotopic autotransplantation using ovarian cortex into the retroperitoneal iliac fossa or omentum in primates.

  17. Determination of Death: A Discussion on Responsible Scholarship, Clinical Practices, and Public Engagement.

    PubMed

    Racine, Eric; Jox, Ralf J; Bernat, James L; Dabrock, Peter; Gardiner, Dale; Marckmann, Georg; Rid, Annette; Rodriguez-Arias, David; Schmitten, Rgen In; Schöne-Seifert, Bettina

    2015-01-01

    The concept and determination of death by neurological or cardio-circulatory criteria play a crucial role for medical practice, society, and the law. Academic debates on death determination have regained momentum, and recent cases involving the neurological determination of death ("brain death") in the United States have sparked sustained public debate. The determination of death by neurological criterion (irreversible cessation of the whole brain or of the brain stem) is medically practiced in at least 80 countries. However, academic debates persist about the conceptual and scientific validity of death determined by neurological criterion. The cardio-circulatory criterion, which permits organ donation following cardio-circulatory arrest, has also recently been challenged. Given the presence of academic debates, several questions ensue about the responsible conduct of clinicians and scholars involved in clinical practices and academic research. This article identifies tension points for responsible practices in the domains of scholarship, clinical practice, and public discourse and formulates suggestions to stimulate further dialogue on responsible practices and to identify questions in need of further research.

  18. Determination of Relative Response Factors of Cefazolin Impurities by Quantitative NMR.

    PubMed

    Liu, Shuyu; Yao, Shangchen; Zhang, Hailing; Hu, Changqin

    2016-11-16

    The relative response factors (RRFs) of ten cefazolin impurities were determined by quantitative nuclear magnetic resonance (qNMR) and high-performance liquid chromatography (HPLC) equipped with an ultraviolet (UV) detector. The purities of these ten cefazolin impurities were successfully measured by qNMR for the purpose of RRFs determination by HPLC. The RRF values and their uncertainties determined by the two approaches are comparable. While the qNMR approach is effective and makes it easier to determine the RRFs for impurities, it also has the advantage of allowing the universal detection of protons without the limitations of common mass detectors. The use of qNMR provides a reliable and universal method for the RRF determination of impurities.

  19. RUNX3 is inactivated by promoter hypermethylation in malignant transformation of ovarian endometriosis.

    PubMed

    Guo, Cuishan; Ren, Fang; Wang, Danbo; Li, Yan; Liu, Kuiran; Liu, Shuang; Chen, Peng

    2014-12-01

    The aim of the present study was to investigate the role of epigenetic inactivation of the runt-related transcription factor 3 gene (RUNX3) in the malignant transformation of ovarian endometriosis. Samples obtained by microdissection and scraping included 30 malignant ovarian endometriotic cyst tissues and 30 corresponding eutopic endometrium tissues from the endometriosis-associated ovarian carcinoma (EAOC) group, 19 benign ovarian endometriotic cyst tissues and 22 corresponding eutopic endometrium tissues from the endometriosis (EM) group and 22 normal eutopic endometrium tissues from the control endometrium (CE) group. RUNX3 methylation status was determined by methylation-specific PCR and bisulfite sequencing, while levels of RUNX3 and ERα protein expression were evaluated using immunohistochemistry. The percentage of RUNX3 methylation and negative RUNX3 protein expression in the malignant ovarian endometriotic cysts from the EAOC group was significantly higher than that in the benign ovarian endometriotic cysts from the EM group. The percentage of RUNX3 methylation and negative RUNX3 protein expression in the eutopic endometrium from the EAOC group was significantly higher than that in the EM and CE groups. An inverse correlation between positive RUNX3 protein expression and methylation was observed and a positive correlation was shown between RUNX3 methylation and ERα protein expression. In the malignant ovarian endometriotic cysts from the EAOC group, there was no significant correlation between methylation frequency of the RUNX3 gene and histological type. However, the percentage of RUNX3 gene methylation was significantly higher in the tissue samples from patients with surgical stage IC EAOC than the percentage in patients with stage IA and IB disease. These results suggest that RUNX3 inactivation by promoter hypermethylation plays a role in the progression of malignant transformation of ovarian EM and is closely related to estrogen metabolism. Negative

  20. Effect of histone deacetylase inhibitors on cell apoptosis and expression of the tumor suppressor genes RUNX3 and ARHI in ovarian tumors.

    PubMed

    Zhang, Lan; Liu, Peishu; Li, Hua; Xue, Fuying

    2013-05-01

    The aim of this study was to investigate the expression of Runt box 3 (RUNX3) and aplasia Ras homolog member I (ARHI) in ovarian tumors, and the effects of histone deacetylase inhibitors (HDACIs) on the expression of these genes and the growth of ovarian cancer cells. The mRNA expression of the RUNX3 and ARHI genes in normal ovaries and ovarian tumors was determined using reverse transcription polymerase chain reaction (RT-PCR). The effects of HDACIs on RUNX3 and ARHI expression in four ovarian cancer cell lines (SKOV3, A2780, COC1 and OC3) were determined using RT-PCR and the MTT assay. The expression of RUNX3 and ARHI in normal ovarian cells was 86 and 100%, respectively. Although the two genes were downregulated in ovarian tumors, the extent of downregulation differed. The expression of RUNX3 and ARHI was correlated with the degree of tumor malignancy (P<0.05). ARHI was expressed in all four ovarian cancer cell lines, whereas RUNX3 was expressed only in the OC3 cell line. Treatment with HDACIs upregulated the expression of ARHI and RUNX3 in the SKOV3 cell line only. In A2780 cells, HDACIs upregulated ARHI expression only in the presence of trichostatin A (TSA) plus cisplatin. HDACIs induced significant apoptosis in ovarian cancer cells, which was inversely correlated with the concentration and duration of treatment (P<0.05). In conclusion, RUNX3 and ARHI were shown to be expressed in normal ovarian cells; however, their expression was downregulated or lost in ovarian tumor cells. The combined detection of ARHI and RUNX3 expression may offer improved prediction and monitoring of ovarian malignancies. HDACIs were revealed to inhibit the growth of ovarian tumor cells and may constitute a novel therapeutic option for ovarian tumors.

  1. Overexpression of HE4 (human epididymis protein 4) enhances proliferation, invasion and metastasis of ovarian cancer

    PubMed Central

    Wang, Huimin; Tan, Mingzi; Schwab, Carlton L.; Deng, Lu; Gao, Jian; Hao, Yingying; Li, Xiao; Gao, Song; Liu, Juanjuan; Lin, Bei

    2016-01-01

    Overexpression of Human epididymis protein 4 (HE4) related with a role in ovarian cancer tumorigenesis while little is known about the molecular mechanism alteration by HE4 up regulation. Here we reported that overexpressed HE4 promoted ovarian cancer cells proliferation, invasion and metastasis. Furthermore, human whole genome gene expression profile microarrays revealed that 231 differentially expressed genes (DEGs) were altered in response to HE4, in which MAPK signaling, ECM receptor, cell cycle, steroid biosynthesis pathways were involved. The findings suggested that overexpressed HE4 played an important role in ovarian cancer progression and metastasis and that HE4 has the potential to serve as a novel therapeutic target for ovarian cancer. PMID:26575020

  2. Grid Inertial Response-Based Probabilistic Determination of Energy Storage System Capacity Under High Solar Penetration

    DOE PAGES

    Yue, Meng; Wang, Xiaoyu

    2015-07-01

    It is well-known that responsive battery energy storage systems (BESSs) are an effective means to improve the grid inertial response to various disturbances including the variability of the renewable generation. One of the major issues associated with its implementation is the difficulty in determining the required BESS capacity mainly due to the large amount of inherent uncertainties that cannot be accounted for deterministically. In this study, a probabilistic approach is proposed to properly size the BESS from the perspective of the system inertial response, as an application of probabilistic risk assessment (PRA). The proposed approach enables a risk-informed decision-making processmore » regarding (1) the acceptable level of solar penetration in a given system and (2) the desired BESS capacity (and minimum cost) to achieve an acceptable grid inertial response with a certain confidence level.« less

  3. Determination of Flaw Size and Depth From Temporal Evolution of Thermal Response

    NASA Technical Reports Server (NTRS)

    Winfree, William P.; Zalameda, Joseph N.; Cramer, Elliott; Howell, Patricia A.

    2015-01-01

    Simple methods for reducing the pulsed thermographic responses of flaws have tended to be based on either the spatial or temporal response. This independent assessment limits the accuracy of characterization. A variational approach is presented for reducing the thermographic data to produce an estimated size for a flaw that incorporates both the temporal and spatial response to improve the characterization. The size and depth are determined from both the temporal and spatial thermal response of the exterior surface above a flaw and constraints on the length of the contour surrounding the delamination. Examples of the application of the technique to simulation and experimental data acquired are presented to investigate the limitations of the technique.

  4. Grid Inertial Response-Based Probabilistic Determination of Energy Storage System Capacity Under High Solar Penetration

    SciTech Connect

    Yue, Meng; Wang, Xiaoyu

    2015-07-01

    It is well-known that responsive battery energy storage systems (BESSs) are an effective means to improve the grid inertial response to various disturbances including the variability of the renewable generation. One of the major issues associated with its implementation is the difficulty in determining the required BESS capacity mainly due to the large amount of inherent uncertainties that cannot be accounted for deterministically. In this study, a probabilistic approach is proposed to properly size the BESS from the perspective of the system inertial response, as an application of probabilistic risk assessment (PRA). The proposed approach enables a risk-informed decision-making process regarding (1) the acceptable level of solar penetration in a given system and (2) the desired BESS capacity (and minimum cost) to achieve an acceptable grid inertial response with a certain confidence level.

  5. The effect of the immune system on ovarian function and features of ovarian germline stem cells.

    PubMed

    Ye, Haifeng; Li, Xiaoyan; Zheng, Tuochen; Liang, Xia; Li, Jia; Huang, Jian; Pan, Zezheng; Zheng, Yuehui

    2016-01-01

    In addition to its role in maintaining organism homeostasis, the immune system also plays a crucial role in the modulation of ovarian function, as it regulates ovarian development, follicular maturation, ovulation and the formation of the corpus luteum. Ovarian germline stem cells are pluripotent stem cells derived from the ovarian cortex that can differentiate into ovarian germ cells and primary granulosa cells. Recent work has demonstrated that the proliferation and differentiation of ovarian germline stem cells is regulated in part by immune cells and their secreted factors. This paper reviews the role of the immune system in the regulation of ovarian function, the relationship between immune components and ovarian germline stem cells and current research efforts in this field.

  6. Effect of diffusion limitations on multianalyte determination from biased biosensor response.

    PubMed

    Baronas, Romas; Kulys, Juozas; Lančinskas, Algirdas; Zilinskas, Antanas

    2014-03-07

    The optimization-based quantitative determination of multianalyte concentrations from biased biosensor responses is investigated under internal and external diffusion-limited conditions. A computational model of a biocatalytic amperometric biosensor utilizing a mono-enzyme-catalyzed (nonspecific) competitive conversion of two substrates was used to generate pseudo-experimental responses to mixtures of compounds. The influence of possible perturbations of the biosensor signal, due to a white noise- and temperature-induced trend, on the precision of the concentration determination has been investigated for different configurations of the biosensor operation. The optimization method was found to be suitable and accurate enough for the quantitative determination of the concentrations of the compounds from a given biosensor transient response. The computational experiments showed a complex dependence of the precision of the concentration estimation on the relative thickness of the outer diffusion layer, as well as on whether the biosensor operates under diffusion- or kinetics-limited conditions. When the biosensor response is affected by the induced exponential trend, the duration of the biosensor action can be optimized for increasing the accuracy of the quantitative analysis.

  7. In vitro antibody response to a distinct antigenic determinant of Escherichia coli β-D-galactosidase

    PubMed Central

    Macario, A. J. L.; De Macario, E. Conway

    1974-01-01

    The anti-β-D-galactosidase activating antibody response in lymph node fragment cultures was investigated in an attempt to understand the mechanism determining the magnitude of an immune response towards a natural hapten, which occurs only once in each antigen molecule, under in vitro conditions that preserve the histology of the responding tissue. Fragments were individually challenged for defined time periods, and washed; cultures with one and two fragments were then set up. Co-cultivation of fragments produced titres higher than predicted from results in single fragment cultures. This happened even when the latter cultures produced low titres because of excessive antigen dosages. Co-cultivation of fragments also improved the duration of the antibody response. These effects appeared to correlate with the number of memory cells present in the fragments at the beginning of the cultures. These observations, together with data obtained by manipulating different doses and times of antigen exposure suggest that collaboration between cells and determinants with different specificities may occur, not only in the initial induction, but also in the sequential stimulation of antibody-forming clones. It is postulated that the co-operative mechanism shown to act in the initiation of the antibody response by cell suspensions toward polyvalent artificial conjugates may also operate when intact lymphoid tissue is reached by a single bacterial determinant in its natural molecular configuration PMID:4136807

  8. Non-steady response of BOD biosensor for the determination of biochemical oxygen demand in wastewater.

    PubMed

    Velling, Siiri; Mashirin, Alexey; Hellat, Karin; Tenno, Toomas

    2011-01-01

    A biochemical oxygen demand (BOD) biosensor for effective and expeditious BOD(7) estimations was constructed and the non-steady phase of the output signal was extensively studied. The modelling approach introduced allows response curve reconstruction and a curve fitting procedure of good quality, resulting in parameters indicating the relationship between response and organic substrate concentration and stability properties of the BOD biosensor. Also, the immobilization matrixes of different thicknesses were characterized to determine their suitability for bio-sensing measurements in non-stationary conditions, as well as for the determination of the mechanical durability of the BOD biosensor in time. The non-steady response of the experimental output of the BOD biosensor was fitted according to the developed model that enables to determine the stability of the biosensor output and dependency on biodegradable organic substrate concentration. The calibration range of the studied BOD biosensor in OECD synthetic wastewater was 15-110 mg O(2) L(-1). Repeatability tests showed relative standard deviation (RSD) values of 2.8% and 5.8% for the parameter τ(d), characterizing the transient output of the amperometric oxygen sensor in time, and τ(s), describing the dependency of the transient response of the BOD biosensor on organic substrate concentration, respectively. BOD biosensor experiments for the evaluation of the biochemical oxygen demand of easily degradable and refractory municipal wastewater showed good concurrence with traditional BOD(7) analysis.

  9. Perineal powder exposure and the risk of ovarian cancer.

    PubMed

    Cook, L S; Kamb, M L; Weiss, N S

    1997-03-01

    This case-control study evaluated the risk of epithelial ovarian cancer associated with genital exposure to various forms of powder application. Cases included all women aged 20-79 years in three counties of western Washington who were diagnosed with borderline or invasive ovarian cancer from 1986 through 1988; 64.3% of eligible cases were interviewed. A sample of similarly aged women who lived in these counties, identified by random digit dialing, served as controls. The overall response among control women was 68.0%. Information on powder application and other potential risk factors was ascertained during the in-person interview. Overall, ovarian cancer cases (n = 313) were more likely than controls (n = 422) to ever have used powder (age-adjusted relative risk (RR) = 1.5, 95% confidence interval (CI) 1.1-2.0). After adjustment for age and other methods of genital powder application (none vs. any), an elevated relative risk of ovarian cancer was noted only for women with a history of perineal dusting (RR = 1.6, 95% CI 1.1-2.3) or use of genital deodorant spray (RR = 1.9, 95% CI 1.1-3.1). These results offer support for the hypothesis, raised by prior epidemiologic studies, that powder exposure from perineal dusting contributes to the development of ovarian cancer, and they suggest that use of genital deodorant sprays may do so as well. Limitations of the present study include the fairly low proportion of eligible women who participated and the potential differential recall of powder usage.

  10. Ovarian angiosarcoma: a case report and review of the literature

    PubMed Central

    2014-01-01

    Introduction Sarcomas of the ovary can either be histologically pure or can represent components of a more complex tumor. Ovarian angiosarcomas are rare, and probably arise from carcinosarcomas, teratomas or the rich ovarian vasculature. To date, only two small case series have been published, one with four cases and the other with seven. Case presentation A 41-year-old Saudi woman presented to our gynecological clinic with abnormal vaginal bleeding. The initial clinical diagnosis was left ovarian cyst. The results of the remainder of her abdominopelvic examination were normal. Peri-operatively, the left ovarian mass resembled a hemorrhagic solid tumor. It was sent for frozen sectioning, which revealed it was an undifferentiated neoplasm. The final histopathological examination showed a vascular neoplasm showing vasoformative arborizing channels of variable sizes and shapes lined by atypical endothelial cells with intact capsule. Areas of necrosis were seen, along with fused anastomosing solid vascular area. She was diagnosed as having an angiosarcoma of intermediate grade, International Federation of Gynecology and Obstetrics stage IA. Conclusions Patients with ovarian angiosarcomas most commonly present with abdominal pain, however some patients present with distant metastases, often in the lungs. Spread beyond the ovary is present at the time of diagnosis in most reported cases, with disease progression within less than a year after diagnosis. Cases of advanced stage disease behave aggressively and demonstrate poor response to surgery and chemotherapy, with an overall poor prognosis. They have a tendency for local recurrence and metastases, and prognosis is hence poor; the reported five-year survival rate is 10 percent to 35 percent, however, cases confined to the ovary have survived up to nine years. PMID:24520828

  11. Impact of environmental exposures on ovarian function and role of xenobiotic metabolism during ovotoxicity

    SciTech Connect

    Bhattacharya, Poulomi; Keating, Aileen F.

    2012-06-15

    The mammalian ovary is a heterogeneous organ and contains oocyte-containing follicles at varying stages of development. The most immature follicular stage, the primordial follicle, comprises the ovarian reserve and is a finite number, defined at the time of birth. Depletion of all follicles within the ovary leads to reproductive senescence, known as menopause. A number of chemical classes can destroy follicles, thus hastening entry into the menopausal state. The ovarian response to chemical exposure can determine the extent of ovotoxicity that occurs. Enzymes capable of bioactivating as well as detoxifying xenobiotics are expressed in the ovary and their impact on ovotoxicity has been partially characterized for trichloroethylene, 7,12-dimethylbenz[a]anthracene, and 4-vinylcyclohexene. This review will discuss those studies, as well as illustrate where knowledge gaps remain for chemicals that have also been established as ovotoxicants. -- Highlights: ► Summary of ovotoxicant action during ovotoxicity. ► Discussion of impact of biotransformation on chemical toxicity. ► Identification of knowledge gaps in chemical metabolism.

  12. The side population of ovarian cancer cells defines a heterogeneous compartment exhibiting stem cell characteristics.

    PubMed

    Boesch, Maximilian; Zeimet, Alain G; Reimer, Daniel; Schmidt, Stefan; Gastl, Guenther; Parson, Walther; Spoeck, Franziska; Hatina, Jiri; Wolf, Dominik; Sopper, Sieghart

    2014-08-30

    Cancer stem cells (CSC) are believed to be involved in tumor evasion of classical antitumor therapies and have thus become an attractive target for further improvement of anticancer strategies. However, the existence and identity of CSC are still a matter of controversy. In a systematic screen of 13 ovarian cancer cell lines we show that cells with stem cell properties are reliably detectable as a minor population, characterized by ABC transporter expression resulting in the side population (SP) phenotype. In different cell lines, either ABCG2 or ABCB1 was found to be responsible for this effect. Purified SP cells featured virtually all characteristics of bona fide CSC, including clonogenicity, asymmetric division and high tumorigenicity in vivo. Using in-depth phenotyping by multicolor flow cytometry, we found that among the investigated ovarian cancer cell lines the SP compartment exhibits tremendous heterogeneity and is composed of multiple phenotypically distinct subpopulations. Thus, our study confirms previous results showing that CSC are contained within the SP. However, the exact identity of the CSC is still disguised by the high complexity of the CSC-containing compartment. Further functional studies are needed to determine whether a single cellular subset can unambiguously be defined as CSC or whether multiple stem cell-like cells with different properties coexist. Moreover, the observed heterogeneity may reflect a high level of plasticity and likely influences tumor progression, escape from immune-surveillance and development of resistance to anticancer therapies and should therefore be considered in the development of new treatment strategies.

  13. The side population of ovarian cancer cells defines a heterogeneous compartment exhibiting stem cell characteristics

    PubMed Central

    Boesch, Maximilian; Zeimet, Alain G.; Reimer, Daniel; Schmidt, Stefan; Gastl, Guenther; Parson, Walther; Spoeck, Franziska; Hatina, Jiri

    2014-01-01

    Cancer stem cells (CSC) are believed to be involved in tumor evasion of classical antitumor therapies and have thus become an attractive target for further improvement of anticancer strategies. However, the existence and identity of CSC are still a matter of controversy. In a systematic screen of 13 ovarian cancer cell lines we show that cells with stem cell properties are reliably detectable as a minor population, characterized by ABC transporter expression resulting in the side population (SP) phenotype. In different cell lines, either ABCG2 or ABCB1 was found to be responsible for this effect. Purified SP cells featured virtually all characteristics of bona fide CSC, including clonogenicity, asymmetric division and high tumorigenicity in vivo. Using in-depth phenotyping by multicolor flow cytometry, we found that among the investigated ovarian cancer cell lines the SP compartment exhibits tremendous heterogeneity and is composed of multiple phenotypically distinct subpopulations. Thus, our study confirms previous results showing that CSC are contained within the SP. However, the exact identity of the CSC is still disguised by the high complexity of the CSC-containing compartment. Further functional studies are needed to determine whether a single cellular subset can unambiguously be defined as CSC or whether multiple stem cell-like cells with different properties coexist. Moreover, the observed heterogeneity may reflect a high level of plasticity and likely influences tumor progression, escape from immune-surveillance and development of resistance to anticancer therapies and should therefore be considered in the development of new