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Sample records for adequate ovarian response

  1. 10 CFR 1304.114 - Responsibility for maintaining adequate safeguards.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Responsibility for maintaining adequate safeguards. 1304.114 Section 1304.114 Energy NUCLEAR WASTE TECHNICAL REVIEW BOARD PRIVACY ACT OF 1974 § 1304.114 Responsibility for maintaining adequate safeguards. The Board has the responsibility for maintaining...

  2. 10 CFR 1304.114 - Responsibility for maintaining adequate safeguards.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Responsibility for maintaining adequate safeguards. 1304.114 Section 1304.114 Energy NUCLEAR WASTE TECHNICAL REVIEW BOARD PRIVACY ACT OF 1974 § 1304.114 Responsibility for maintaining adequate safeguards. The Board has the responsibility for maintaining...

  3. 10 CFR 1304.114 - Responsibility for maintaining adequate safeguards.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 4 2014-01-01 2014-01-01 false Responsibility for maintaining adequate safeguards. 1304.114 Section 1304.114 Energy NUCLEAR WASTE TECHNICAL REVIEW BOARD PRIVACY ACT OF 1974 § 1304.114 Responsibility for maintaining adequate safeguards. The Board has the responsibility for maintaining...

  4. 10 CFR 1304.114 - Responsibility for maintaining adequate safeguards.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 4 2013-01-01 2013-01-01 false Responsibility for maintaining adequate safeguards. 1304.114 Section 1304.114 Energy NUCLEAR WASTE TECHNICAL REVIEW BOARD PRIVACY ACT OF 1974 § 1304.114 Responsibility for maintaining adequate safeguards. The Board has the responsibility for maintaining...

  5. 10 CFR 1304.114 - Responsibility for maintaining adequate safeguards.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 false Responsibility for maintaining adequate safeguards. 1304.114 Section 1304.114 Energy NUCLEAR WASTE TECHNICAL REVIEW BOARD PRIVACY ACT OF 1974 § 1304.114 Responsibility for maintaining adequate safeguards. The Board has the responsibility for maintaining...

  6. 4 CFR 200.14 - Responsibility for maintaining adequate safeguards.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... identifiable personal data and automated systems shall be adequately trained in the security and privacy of... records in which identifiable personal data are processed or maintained, including all reports and output... personal records or data; must minimize, to the extent practicable, the risk that skilled technicians...

  7. 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.

  8. Ensuring smokers are adequately informed: reflections on consumer rights, manufacturer responsibilities, and policy implications

    PubMed Central

    Chapman, S; Liberman, J

    2005-01-01

    The right to information is a fundamental consumer value. Following the advent of health warnings, the tobacco industry has repeatedly asserted that smokers are fully informed of the risks they take, while evidence demonstrates widespread superficial levels of awareness and understanding. There remains much that tobacco companies could do to fulfil their responsibilities to inform smokers. We explore issues involved in the meaning of "adequately informed" smoking and discuss some of the key policy and regulatory implications. We use the idea of a smoker licensing scheme—under which it would be illegal to sell to smokers who had not demonstrated an adequate level of awareness—as a device to explore some of these issues. We also explore some of the difficulties that addiction poses for the notion that smokers might ever voluntarily assume the risks of smoking. PMID:16046703

  9. Ensuring smokers are adequately informed: reflections on consumer rights, manufacturer responsibilities, and policy implications.

    PubMed

    Chapman, S; Liberman, J

    2005-08-01

    The right to information is a fundamental consumer value. Following the advent of health warnings, the tobacco industry has repeatedly asserted that smokers are fully informed of the risks they take, while evidence demonstrates widespread superficial levels of awareness and understanding. There remains much that tobacco companies could do to fulfil their responsibilities to inform smokers. We explore issues involved in the meaning of "adequately informed" smoking and discuss some of the key policy and regulatory implications. We use the idea of a smoker licensing scheme-under which it would be illegal to sell to smokers who had not demonstrated an adequate level of awareness-as a device to explore some of these issues. We also explore some of the difficulties that addiction poses for the notion that smokers might ever voluntarily assume the risks of smoking. PMID:16046703

  10. 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

  11. The adequate stimulus for avian short latency vestibular responses to linear translation

    NASA Technical Reports Server (NTRS)

    Jones, T. A.; Jones, S. M.; Colbert, S.

    1998-01-01

    Transient linear acceleration stimuli have been shown to elicit eighth nerve vestibular compound action potentials in birds and mammals. The present study was undertaken to better define the nature of the adequate stimulus for neurons generating the response in the chicken (Gallus domesticus). In particular, the study evaluated the question of whether the neurons studied are most sensitive to the maximum level of linear acceleration achieved or to the rate of change in acceleration (da/dt, or jerk). To do this, vestibular response thresholds were measured as a function of stimulus onset slope. Traditional computer signal averaging was used to record responses to pulsed linear acceleration stimuli. Stimulus onset slope was systematically varied. Acceleration thresholds decreased with increasing stimulus onset slope (decreasing stimulus rise time). When stimuli were expressed in units of jerk (g/ms), thresholds were virtually constant for all stimulus rise times. Moreover, stimuli having identical jerk magnitudes but widely varying peak acceleration levels produced virtually identical responses. Vestibular response thresholds, latencies and amplitudes appear to be determined strictly by stimulus jerk magnitudes. Stimulus attributes such as peak acceleration or rise time alone do not provide sufficient information to predict response parameter quantities. Indeed, the major response parameters were shown to be virtually independent of peak acceleration levels or rise time when these stimulus features were isolated and considered separately. It is concluded that the neurons generating short latency vestibular evoked potentials do so as "jerk encoders" in the chicken. Primary afferents classified as "irregular", and which traditionally fall into the broad category of "dynamic" or "phasic" neurons, would seem to be the most likely candidates for the neural generators of short latency vestibular compound action potentials.

  12. 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

  13. The rat adequately reflects human responses to exercise in blood biochemical profile: a comparative study

    PubMed Central

    Goutianos, Georgios; Tzioura, Aikaterini; Kyparos, Antonios; Paschalis, Vassilis; Margaritelis, Nikos V; Veskoukis, Aristidis S; Zafeiridis, Andreas; Dipla, Konstantina; Nikolaidis, Michalis G; Vrabas, Ioannis S

    2015-01-01

    Animal models are widely used in biology and the findings of animal research are traditionally projected to humans. However, recent publications have raised concerns with regard to what extent animals and humans respond similar to physiological stimuli. Original data on direct in vivo comparison between animals and humans are scarce and no study has addressed this issue after exercise. We aimed to compare side by side in the same experimental setup rat and human responses to an acute exercise bout of matched intensity and duration. Rats and humans ran on a treadmill at 86% of maximal velocity until exhaustion. Pre and post exercise we measured 30 blood chemistry parameters, which evaluate iron status, lipid profile, glucose regulation, protein metabolism, liver, and renal function. ANOVA indicated that almost all biochemical parameters followed a similar alteration pattern post exercise in rats and humans. In fact, there were only 2/30 significant species × exercise interactions (in testosterone and globulins), indicating different responses to exercise between rats and humans. On the contrary, the main effect of exercise was significant in 15/30 parameters and marginally nonsignificant in other two parameters (copper, P = 0.060 and apolipoprotein B, P = 0.058). Our major finding is that the rat adequately mimics human responses to exercise in those basic blood biochemical parameters reported here. The physiological resemblance of rat and human blood responses after exercise to exhaustion on a treadmill indicates that the use of blood chemistry in rats for exercise physiology research is justified. PMID:25677548

  14. PG medical training and accreditation: responsibility of the government for the adequate health service delivery.

    PubMed

    Bhattarai, M D

    2012-09-01

    On one hand there is obvious inadequate health coverage to the rural population and on the other hand the densely populated urban area is facing the triple burden of increasing non-communicable and communicable health problems and the rising health cost. The postgraduate medical training is closely interrelated with the adequate health service delivery and health economics. In relation to the prevailing situation, the modern medical education trend indicates the five vital issues. These are i). Opportunity needs to be given to all MBBS graduates for General Specialist and Sub-Specialist Training inside the country to complete their medical education, ii). Urgent need for review of PG residential training criteria including appropriate bed and teacher criteria as well as entry criteria and eligibility criteria, iii). Involvement of all available units of hospitals fulfilling the requirements of the residential PG training criteria, iv). PG residential trainings involve doing the required work in the hospitals entitling them full pay and continuation of the service without any training fee or tuition fee, and v). Planning of the proportions of General Specialty and Sub-Specialty Training fields, particularly General Practice (GP) including its career and female participation. With increased number of medical graduates, now it seems possible to plan for optimal health coverage to the populations with appropriate postgraduate medical training. The medical professionals and public health workers must make the Government aware of the vital responsibility and the holistic approach required.

  15. Ultrasonographic predictors of response of European eels (Anguilla anguilla) to hormonal treatment for induction of ovarian development.

    PubMed

    Müller, Anna V; McEvoy, Fintan J; Tomkiewicz, Jonna; Politis, Sebastian N; Amigo, José M

    2016-05-01

    OBJECTIVE To examine ultrasonographic predictors of ovarian development in European eels (Anguilla anguilla) undergoing hormonal treatment for assisted reproduction. ANIMALS 83 female European eels. PROCEDURES Eels received weekly IM injections of salmon pituitary extract (first injection = week 1). Ultrasonography of the ovaries was performed twice during hormonal treatment (weeks 7 and 11). Eels were identified on the basis of body weight as having an adequate response by weeks 14 to 20 or an inadequate response after injections for 21 weeks. Eels were euthanized at the end of the experiment and classified by use of ovarian histologic examination. Ovarian cross-sectional area and size of eel (ie, length (3) ) were used to classify eels (fast responder, slow responder, or nonresponder) and to calculate an ultrasonographic-derived gonadosomatic index. Gray-level co-occurrence matrices were calculated from ovarian images, and 22 texture features were calculated from these matrices. RESULTS The ultrasonographic-derived gonadosomatic index differed significantly between fast responders and slow responders or nonresponders at both weeks 7 and 11. Principal component analysis revealed a pattern of separation between the groups, and partial least squares discriminant analysis revealed signals in the ovarian texture that discriminated females that responded to treatment from those that did not. CONCLUSIONS AND CLINICAL RELEVANCE Ovarian texture information in addition to morphometric variables can enhance ultrasonographic applications for assisted reproduction of eels and potentially other fish species. This was a novel, nonlethal method for classifying reproductive response of eels and the first objective texture analysis performed on ultrasonographic images of the gonads of fish. PMID:27111015

  16. Response to ovarian stimulation in patients facing gonadotoxic therapy.

    PubMed

    Johnson, Lauren N C; Dillon, Katherine E; Sammel, Mary D; Efymow, Brenda L; Mainigi, Monica A; Dokras, Anuja; Gracia, Clarisa R

    2013-04-01

    Chemotherapy naïve patients undergoing embryo/oocyte banking for fertility preservation (FP) were assessed for response to ovarian stimulation. Fifty FP patients facing gonadotoxic therapy were matched by age, race, cycle number, date of stimulation and fertilization method to patients undergoing IVF for infertility or oocyte donation. There were no differences in baseline FSH, anti-Müllerian hormone, antral follicle count and total gonadotrophin dose. FP patients had more immature oocytes (2.2 versus 1.1; P=0.03) and lower fertilization rates per oocyte retrieved (52% versus 70%; P=0.002). There were no differences in numbers of oocytes retrieved, mature oocytes or fertilized embryos. Subgroup analysis revealed that FP patients taking letrozole required higher gonadotrophin doses (3077IU versus 2259IU; P=0.0477) and had more immature oocytes (3.4 versus 1.2; P=0.03) than matched controls. There were no differences in gonadotrophin dose or oocyte immaturity among FP patients not taking letrozole. Overall, chemotherapy naïve FP patients had similar ovarian reserve, response to stimulation and oocyte and embryo yield compared to controls. Patients who received letrozole required higher gonadotrophin doses and produced more immature oocytes, suggesting that response to ovarian stimulation may be impaired in patients with hormone-sensitive cancers receiving letrozole. With improvement in cancer survival rates, there has been a shift in attention toward management of long-term consequences of cancer therapy, including infertility. Many young women with cancer, particularly those who will be treated with chemotherapy, pursue fertility preservation (FP) strategies for the purpose of banking oocytes or embryos for future use. We examined patients with no prior exposure to chemotherapy who underwent IVF to freeze embryos or oocytes for FP. Fifty FP patients were identified and matched to healthy controls by age, race, cycle number, date of stimulation and fertilization

  17. Broadband inversion of 1J(CC) responses in 1,n-ADEQUATE spectra.

    PubMed

    Reibarkh, Mikhail; Williamson, R Thomas; Martin, Gary E; Bermel, Wolfgang

    2013-11-01

    Establishing the carbon skeleton of a molecule greatly facilitates the process of structure elucidation, both manual and computer-assisted. Recent advances in the family of ADEQUATE experiments demonstrated their potential in this regard. 1,1-ADEQUATE, which provides direct (13)C-(13)C correlation via (1)J(CC), and 1,n-ADEQUATE, which typically yields (3)J(CC) and (1)J(CC) correlations, are more sensitive and more widely applicable experiments than INADEQUATE and PANACEA. A recently reported modified pulse sequence that semi-selectively inverts (1)J(CC) correlations in 1,n-ADEQUATE spectra provided a significant improvement, allowing (1)J(CC) and (n)J(CC) correlations to be discerned in the same spectrum. However, the reported experiment requires a careful matching of the amplitude transfer function with (1)J(CC) coupling constants in order to achieve the inversion, and even then some (1)J(CC) correlations could still have positive intensity due to the oscillatory nature of the transfer function. Both shortcomings limit the practicality of the method. We now report a new, dual-optimized inverted (1)J(CC) 1,n-ADEQUATE experiment, which provides more uniform inversion of (1)J(CC) correlations across the range of 29-82 Hz. Unlike the original method, the dual optimization experiment does not require fine-tuning for the molecule's (1)J(CC) coupling constant values. Even more usefully, the dual-optimized version provides up to two-fold improvement in signal-to-noise for some long-range correlations. Using modern, cryogenically-cooled probes, the experiment can be successfully applied to samples of ~1 mg under favorable circumstances. The improvements afforded by dual optimization inverted (1)J(CC) 1,n-ADEQUATE experiment make it a useful and practical tool for NMR structure elucidation and should facilitate the implementation and utilization of the experiment.

  18. Reproductive plasticity, ovarian dynamics and maternal effects in response to temperature and flight in Pararge aegeria.

    PubMed

    Gibbs, Melanie; Van Dyck, Hans; Karlsson, Bengt

    2010-09-01

    In nature, ovipositing females may be subjected to multiple extrinsic and intrinsic environmental factors simultaneously. To adequately assess a species response to environmental conditions during oviposition it may therefore be necessary to consider the interaction between multiple intrinsic and extrinsic factors simultaneously. Using the butterfly, Pararge aegeria, this study examined the combined effects of extrinsic (temperature and flight) and intrinsic (body mass and age) factors on ovarian dynamics, egg provisioning and reproductive output, and explored how these effects subsequently influenced offspring fitness when egg-stage development occurred in a low humidity environment. Both temperature- and flight-mediated plasticity in female reproductive output was observed, and there were strong temperature by flight interaction effects for the traits oocyte size and egg mass. As females aged, mean daily fecundity differed across temperature treatments, but not across flight treatments. Overall, temperature had more pronounced effects on ovarian dynamics than flight. Flight mainly influenced egg mass via changes in relative water content. A mismatch between the physiological response of females to high temperature and the requirements of their offspring had a negative impact on offspring fitness via effects on egg hatching success.

  19. Electrographic correlates of adequate and erroneous responses evoked by conditioned signals of different functional signs during operant learning in dogs.

    PubMed

    Dumenko, V N; Kozlov, M K

    2006-01-01

    Power spectra over the frequency range 1-225 Hz in short-term (less than 1 sec) EEG reactions arising in different areas of the cerebral cortex in response to presentation of differential signals were investigated in dogs during operant feeding behavior in conditions of both adequate and erroneous responses. The energy levels of these reactions decreased several-fold as compared with responses to positive signals, mainly because of frequencies in the high-frequency range (90-225 Hz), where power was greater than not only the traditional range of 1-30 Hz, but also the gamma range of 30-80 Hz. The frequency composition of EEG reactions in adequate responses was determined by a series of discrete frequency subgroups belonging predominantly to the high-frequency band. In erroneous reactions, the discrete structure of the corresponding EEG reactions was lost.

  20. Influence of varied progestogen treatments on ovarian follicle status and subsequent ovarian superstimulatory responses in cows.

    PubMed

    D'Occhio, M J; Niasari-Naslaji, A; Kinder, J E

    1997-01-01

    The influence of ovarian follicle status and follicle dominance on the response to superstimulatory treatment with FSH was examined in cows. In Experiment 1, oestrus was synchronised using Crestar and on Days 4-6 of the ensuing oestrous cycle cows were assigned to: Group NO (n = 9), control, endogenous CL and no treatment; Group N1 (n = 15), injected with a luteolytic dose of cloprostenol (500 micrograms) and implanted with one implant (3 mg) of the synthetic progestogen, norgestomet; Group N8 (n = 18), injected with 500 micrograms cloprostenol and implanted with eight (24 mg) implants of norgestomet. On Days 9-11, seven implants were removed from six cows in Group N8 and these cows, plus eight Group N1 and all Group N0 cows, were superstimulated with porcine FSH (Folltropin-V) over 4 days (360 mg total dose). The remaining implants were removed from cows in Groups N1 and N8 on Days 11-13, and all cows received 500 micrograms cloprostenol. Numbers and sizes of ovarian follicles, and CL, were recorded by trans-rectal ultrasonography; the largest follicle > 10 mm in diameter was considered morphologically dominant (DF). On Days 9-11, the proportions of cows with a DF were: Group N0, 3/9; Group N1, 14/15; Group N8, 0/18. Total follicles on the 4th day of FSH treatment were greater (P < 0.05) for cows in Group N1 (21.6 +/- 4.2) compared with Group N0 (10.9 +/- 2.4), with cows in Group N8 (13.2 +/- 0.9) not different from the other two groups. Subsequent numbers of CL were lower (P < 0.05) for cows in Group N1 (5.0 +/- 1.3) compared with Group N0 (9.4 +/- 2.0), with cows in Group N8 (8.5 +/- 1.0) not different from the other two groups. In Experiment 2, oestrus was synchronised in cows and on Days 4-6, cows were assigned to: Group C0 (n = 7), control, endogenous CL and no treatment; Group C3 (n = 6), received three CIDR-B intra-vaginal devices that delivered progesterone. On Days 9-11, two CIDR-B were removed from cows in Group C3 and all cows treated with FSH as in

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

    PubMed Central

    2013-01-01

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

  2. A single nucleotide polymorphism in BMP15 is associated with high response to ovarian stimulation.

    PubMed

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

    2011-07-01

    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 may influence ovarian stimulation outcome. One previous study showed an association between single nucleotide polymorphisms (SNP) in the gene for bone morphogenetic protein 15 (BMP15) and ovarian hyperstimulation syndrome (OHSS). This article presents a retrospective case-controlled genetic-association study designed to test the association between SNP in the BMP15 gene 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 five SNP of interest. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated by a multivariate logistic regression model. We found an association between the BMP15 -9G allele and high response to ovarian stimulation (OR=2.7, 95% CI=1.3-5.7). This association confirms previous findings in a different population and strengthens the case for an association between this SNP and ovarian stimulation outcome.

  3. Adopting adequate leaching requirement for practical response models of basil to salinity

    NASA Astrophysics Data System (ADS)

    Babazadeh, Hossein; Tabrizi, Mahdi Sarai; Darvishi, Hossein Hassanpour

    2016-07-01

    Several mathematical models are being used for assessing plant response to salinity of the root zone. Objectives of this study included quantifying the yield salinity threshold value of basil plants to irrigation water salinity and investigating the possibilities of using irrigation water salinity instead of saturated extract salinity in the available mathematical models for estimating yield. To achieve the above objectives, an extensive greenhouse experiment was conducted with 13 irrigation water salinity levels, namely 1.175 dS m-1 (control treatment) and 1.8 to 10 dS m-1. The result indicated that, among these models, the modified discount model (one of the most famous root water uptake model which is based on statistics) produced more accurate results in simulating the basil yield reduction function using irrigation water salinities. Overall the statistical model of Steppuhn et al. on the modified discount model and the math-empirical model of van Genuchten and Hoffman provided the best results. In general, all of the statistical models produced very similar results and their results were better than math-empirical models. It was also concluded that if enough leaching was present, there was no significant difference between the soil salinity saturated extract models and the models using irrigation water salinity.

  4. Association of follicle stimulating hormone receptor promoter with ovarian response in IVF-ET patients

    PubMed Central

    Dan, Wang; Jing, Gao; Liangbin, Xia; Ting, Zhang; Ying, Zeng

    2015-01-01

    Background: Poor ovarian response phenomenon has been observed in some of the in vitro fertilization-embryo transfer patients. Some investigations found that follicle stimulating hormone receptor (FSHR) gene plays a role in the process, but no direct evidence shows the correlation between genotypes of FSHR and ovarian response. Objective: Exploring the molecular mechanism behind the mutation of FSHR promoter association with ovarian granulosa cells and poor ovarian response. Materials and Methods: This cross sectional study was performed using 158 women undergoing the controlled short program ovarian stimulation for IVF treatment. The 263 bp DNA fragments before the follicle stimulating hormone (FSH) receptor 5' initiation site were sequenced in the patients under IVF cycle, 70 of which had poor ovarian response and 88 showed normal ovarian responses. Results: With a mutation rate of 40%, 63 in 158 cases showed a 29th site G→A point mutation; among the mutated cases, the mutation rate of the poor ovarian responders was significantly higher than the normal group (60% versus 23.9%; χ2=21.450, p<0.001). Besides, the variability was also obvious in antral follicle count, and ovum pick-ups. The estradiol peak values and the number of mature eggs between the two groups had significant difference. However, there was no obvious variability (t=0.457, p=0.324) in the basic FSH values between the two groups (normal group, 7.2±2.3 U/L; mutation group, 7.1±2.0 U/L). Conclusion: The activity of FSHR promoter is significantly affected by the 29th site G→A mutation that will weaken promoter activity and result in poor response to FSH. PMID:26730247

  5. 45 CFR 1159.15 - Who has the responsibility for maintaining adequate technical, physical, and security safeguards...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... adequate technical, physical, and security safeguards to prevent unauthorized disclosure or destruction of... adequate technical, physical, and security safeguards to prevent unauthorized disclosure or destruction of... of maintaining adequate technical, physical, and security safeguards to prevent...

  6. 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

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

    PubMed

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

    2016-09-01

    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

  8. 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

  9. 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.

  10. [Poor Ovarian Response to Stimulation for In Vitro Fertilization].

    PubMed

    Spremović-Radjenović, Svetlana; Bila, Jovan; Gudović, Aleksandra; Vidaković, Snežana; Dokić, Milan; Radunović, Nebojša

    2015-01-01

    The term "poor respond (POR) patients" is used for the group of women who respond badly to usual doses of gonadotropins in in vitro fertilization (IVF) treatments; the consequence is low pregnancy rate. A consensus was reached on the minimal criteria needed to define POR. At least two of the following three features must be present: 1. advanced maternal age (40 years or more) 2. previous POR (3 or less oocytes with a conventional stimulation protocol) 3. abnormal ovarian reserve (AMH 0.5-1.1 ng/ml or AFC 5-7).The aim is to find better therapeutic options for these patients. Increased levels of day 3 follicle stimulating hormone (FSH) and estradiol (E2), as well as decreased levels of anti-Müllerian hormone (AMH) and antral follicle count (AFC), can be used to assess ovarian reserve, as indirect predictive tests. A larger number of well designed, large scale, randomized, controlled trials are needed to assess the efficacy of different management strategies for poor responders: flare up gonadotropin releasing hormone (GnRH) agonist protocols, modified long GnRH agonist mini-dose protocols, luteal initiation GnRH agonist stop protocol, pretreatment with estradiol--GnRH antagonist in luteal phase, natural cycle aspiration or natural cycle aspiration GnRH antagonist controlled, adjuvant therapy with growth hormone or dehydroepiandrosterone (DHEA). The results of up to now used protocols are unsatisfactory and stimulation of the ovulation in poor responders remains a challenge, especially when bearing in mind that in the majority of cases the patients will be menopausal in relatively short period of time.

  11. Analyses of merlin/NF2 connection to FAK inhibitor responsiveness in serous ovarian cancer

    PubMed Central

    Shah, Nina R.; Tancioni, Isabelle; Ward, Kristy K.; Lawson, Christine; Chen, Xiao Lei; Jean, Christine; Sulzmaier, Florian J.; Uryu, Sean; Miller, Nichol L.G.; Connolly, Denise C.; Schlaepfer, David D.

    2014-01-01

    Objective Focal adhesion kinase (FAK) is overexpressed in serous ovarian cancer. Loss of merlin, a product of the neurofibromatosis 2 tumor suppressor gene, is being evaluated as a biomarker for FAK inhibitor sensitivity in mesothelioma. Connections between merlin and FAK in ovarian cancer remain undefined. Methods Nine human and two murine ovarian cancer cell lines were analyzed for growth in the presence of a small molecule FAK inhibitor (PF-271, 0.1 to 1 μM) for 72 h. Merlin was evaluated by immunoblotting and immunostaining of a human ovarian tumor tissue array. Growth of cells was analyzed in an orthotopic tumor model and evaluated in vitro after stable shRNA-mediated merlin knockdown. Results Greater than 50% inhibition of OVCAR8, HEY and ID8-IP ovarian carcinoma cell growth occurred with 0.1 μM PF-271 in anchorage-independent (p<0.001) but not in adherent culture conditions. PF-271-mediated reduction in FAK Y397 phosphorylation occurred independently of growth inhibition. Suspended growth of OVCAR3, OVCAR10, IGROV1, IGROV1-IP, SKOV3, SKOV3-IP, A2780, and 5009-MOVCAR was not affected by 0.1 μM PF-271. Merlin expression did not correlate with serous ovarian tumor grade or stage. PF-271 (30 mg/kg, BID) did not inhibit 5009-MOVCAR tumor growth and merlin knockdown in SKOV3-IP and OVCAR10 cells did not alter suspended cell growth upon PF-271 addition. Conclusions Differential responsiveness to FAK inhibitor treatment were observed. Intrinsic low merlin protein levels correlated with PF-271-mediated anchorage-independent growth inhibition, but reduction in merlin expression did not induce sensitivity to FAK inhibition. Merlin levels may be useful for patient stratification in FAK inhibitor trials. PMID:24786638

  12. Oocyte production and ovarian steroid concentrations of immature rats in response to some commercial gonadotrophin preparations.

    PubMed

    Henderson, K M; Weaver, A; Wards, R L; Ball, K; Lun, S; Mullin, C; McNatty, K P

    1990-01-01

    Four commercial gonadotrophin preparations, namely Folligon, F.S.H.-P., Folltropin and Ovagen, were examined for their effects on oocyte production and ovarian steroid concentrations in immature rats. The ratios of the FSH to LH concentrations of the preparations, determined by radioreceptor assays, were Folligon 5, F.S.H.-P. 18, Folltropin 49 and Ovagen 1090. Forty-eight hours after administering each gonadotrophin preparation to immature rats, ovulation was induced by injection of chorionic gonadotrophin. Twenty-four hours later, oocytes were recovered from the oviducts and counted. Oocytes were produced after injection of chorionic gonadotrophin following a single injection of Folligon (10-50 i.u.). However, no oocytes were produced in response to the other gonadotrophin preparations unless they were administered by continuous infusion (30-1000 micrograms day-1). When given by injection (Folligon) or infusion (others), the gonadotrophin preparations all promoted a dose-dependent increase in mean oocyte production, except at the highest doses when mean oocyte numbers either remained unchanged or declined significantly in the cases of Folligon and F.S.H.-P. The highest mean numbers of oocytes produced in response to Folltropin (48 +/- 9 oocytes, mean +/- s.e.m.) and Ovagen (47 +/- 7) were greater than those attained with Folligon (21 +/- 6) or F.S.H.-P. (31 +/- 5). Mean ovarian weights also increased in a dose-dependent fashion in response to each of the gonadotrophin preparations. Measurements of ovarian steroid concentrations 48 h after the onset of gonadotrophin treatment (i.e. immediately prior to ovulation induction with chorionic gonadotrophin) showed that the gonadotrophin preparations markedly influenced the ratios of ovarian oestradiol-17 beta and androgen (androstenedione plus testosterone) concentrations. At low doses the gonadotrophin preparations increased the ratio of oestradiol-17 beta to androgens, but at the highest doses, with the exception of

  13. 45 CFR 2508.10 - Who has the responsibility for maintaining adequate technical, physical, and security safeguards...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... maintained in a secured room with a locking door. (3) Access to and use of a system of records shall be...) Access to areas where a system of records is stored will be limited to those persons whose duties require... require access to and use of records contained in a system of records are adequately trained to...

  14. 45 CFR 2508.10 - Who has the responsibility for maintaining adequate technical, physical, and security safeguards...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... maintained in a secured room with a locking door. (3) Access to and use of a system of records shall be...) Access to areas where a system of records is stored will be limited to those persons whose duties require... require access to and use of records contained in a system of records are adequately trained to...

  15. 45 CFR 2508.10 - Who has the responsibility for maintaining adequate technical, physical, and security safeguards...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... maintained in a secured room with a locking door. (3) Access to and use of a system of records shall be...) Access to areas where a system of records is stored will be limited to those persons whose duties require... require access to and use of records contained in a system of records are adequately trained to...

  16. Anti-mullerian hormone cut-off values for predicting poor ovarian response to exogenous ovarian stimulation in in-vitro fertilization

    PubMed Central

    Satwik, Ruma; Kochhar, Mohinder; Gupta, Shweta M; Majumdar, Abha

    2012-01-01

    OBJECTIVES: (a) To establish the cut-off levels for anti-Mullerian hormone (AMH) in a population of Indian women that would determine poor response. (b) To determine which among the three ie.,: age, follicle stimulating hormone (FSH), or AMH, is the better determinant of ovarian reserve. STUDY DESIGN: Prospective observational study. SETTING: In vitro fertilization (IVF) unit of a tertiary hospital. MATERIALS AND METHODS: The inclusion criterion was all women who presented to the center for in-vitro fertilization/Intracytoplasmic sperm injection (IVF/ICSI). The exclusion criteria were age >45 years, major medical illnesses precluding IVF or pregnancy, FSH more than 20 IU/L, and failure to obtain consent. The interventions including baseline pelvic scan, day 2/3 FSH, luteinizing hormone (LH), estradiol estimations, and AMH measurement on any random day of cycle were done. Subjects underwent IVF according to long agonist or antagonist protocol regimen. Oocyte recovery was correlated with studied variables. The primary outcome measure was the number of oocytes aspirated (OCR). Three categories of ovarian response were defined: poor response, OCR ≤ 3; average response, OCR between 4 and 15; hyperresponse, OCR > 15. RESULTS: Of the 198 patients enrolled, poor, average, and hyperresponse were observed in 23%, 63%, and 14% respectively. Correlation coefficient for AMH with ovarian response was r = 0.591. Area under the curve (AUCs) for poor response for AMH, subject's age, and FSH were 0.768, 0.624, and 0.635, respectively. The discriminatory level of AMH for prediction of absolute poor response was 2 pmoL/l, with 98% specificity and 20% sensitivity. CONCLUSIONS: AMH fares better than age and FSH in predicting the overall ovarian response and poor response, though it cannot be the absolute predictor of non-responder status. A level of 2 pmol/l is discriminatory for poor response. PMID:23162361

  17. Anti Mullerian Hormone: Ovarian response indicator in young patients receiving Long GnRH Agonist Protocol for Ovarian Stimulation

    PubMed Central

    Jamil, Zehra; Fatima, Syeda Sadia; Rehman, Rehana; Alam, Faiza; Arif, Sara

    2016-01-01

    Objective: Anti Mullerian hormone (AMH) is gaining place as ovarian marker, chiefly in infertility assistance. We explored its correlation with oocytes retrieval after long GnRH agonist protocol for stimulation, in younger and older infertile population. Methods: This retrospective analysis compiled data of 166 females, receiving ICSI treatment from June 2014 to March 2015. Serum FSH, LH, Estadiol, AMH and antral follicle count were assessed. Outcomes were measured as good (5 to 19 oocytes) and bad responders. Results: Higher discriminatory power of AMH (AUROC; 0.771; p < 0.05) was seen in comparison to FSH (0.692; p < 0.05) and AFC (0.690; p < 0.01). AMH reported strongest association with oocyte retrieved (odds ratio of 15.06). Subgroup analysis reported 68.6 % risk of bad response with AMH levels of less than 1.37ng/ml. This association was observed more significant in young infertile patients <35 year of age (r=0.245; p=0.012) versus older population >35 year (r=0.169; p>0.05). Conclusion: Our study reaffirms that serum AMH correlates well with oocytes retrieved, particularly in females younger than 35 years. We suggest incorporation of AMH in baseline assessment of infertile females, who are falsely advised to postpone interventions based on their age and normal FSH levels. PMID:27648045

  18. Anti Mullerian Hormone: Ovarian response indicator in young patients receiving Long GnRH Agonist Protocol for Ovarian Stimulation

    PubMed Central

    Jamil, Zehra; Fatima, Syeda Sadia; Rehman, Rehana; Alam, Faiza; Arif, Sara

    2016-01-01

    Objective: Anti Mullerian hormone (AMH) is gaining place as ovarian marker, chiefly in infertility assistance. We explored its correlation with oocytes retrieval after long GnRH agonist protocol for stimulation, in younger and older infertile population. Methods: This retrospective analysis compiled data of 166 females, receiving ICSI treatment from June 2014 to March 2015. Serum FSH, LH, Estadiol, AMH and antral follicle count were assessed. Outcomes were measured as good (5 to 19 oocytes) and bad responders. Results: Higher discriminatory power of AMH (AUROC; 0.771; p < 0.05) was seen in comparison to FSH (0.692; p < 0.05) and AFC (0.690; p < 0.01). AMH reported strongest association with oocyte retrieved (odds ratio of 15.06). Subgroup analysis reported 68.6 % risk of bad response with AMH levels of less than 1.37ng/ml. This association was observed more significant in young infertile patients <35 year of age (r=0.245; p=0.012) versus older population >35 year (r=0.169; p>0.05). Conclusion: Our study reaffirms that serum AMH correlates well with oocytes retrieved, particularly in females younger than 35 years. We suggest incorporation of AMH in baseline assessment of infertile females, who are falsely advised to postpone interventions based on their age and normal FSH levels.

  19. Reproductive and nutritional management on ovarian response and embryo quality on rabbit does.

    PubMed

    Lorenzo, P L; García-García, R M; Árias-Álvarez, M; Rebollar, P G

    2014-10-01

    Rabbit does in modern rabbitries are under intensive reproductive rhythms. Females are high milk producers with high energetic expenses due to the extensive overlap between lactation and gestation. This situation leads to a negative energy balance with a mobilization of body fat especially in primiparous rabbit does. Poor body condition and poor health status severely affect the reproductive features (fertility rate and lifespan of the doe as well as ovarian physiology). This paper reviews some reproductive and nutritional approaches used in the last years to improve the reproductive performance of rabbit females, mainly focusing on the influence on ovarian response and embryo quality and with emphasis on epigenetic modifications in pre-implantation embryos and offspring consequences. PMID:25277432

  20. 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

  1. Ovarian blood flow responses to electro-acupuncture stimulation at different frequencies and intensities in anaesthetized rats.

    PubMed

    Stener-Victorin, Elisabet; Kobayashi, Rie; Kurosawa, Mieko

    2003-10-31

    The purpose of the present study was to investigate changes in ovarian blood flow (OBF) in response to electro-acupuncture (EA) stimulation at different frequencies and intensities in anaesthetized rats. Whether the ovarian sympathetic nerves were involved in OBF responses was elucidated by severance of the ovarian sympathetic nerves. In addition, how changes in the systemic circulation affected OBF was evaluated by continuously recording blood pressure. OBF was measured on the surface of the left ovary using laser Doppler flowmeter. Acupuncture needles with a diameter of 0.3 mm were inserted bilaterally into the abdominal and the hindlimb muscles and connected to an electrical stimulator. Two frequencies-2 Hz (low) and 80 Hz (high)-with three different intensities-1.5, 3, and 6 mA-were applied for 35 s. Both low- and high-frequency EA at 1.5 mA and high-frequency EA at 3 mA had no effect on OBF or mean arterial blood pressure (MAP). Low-frequency EA at 3 and 6 mA elicited significant increases in OBF. In contrast, high-frequency EA with an intensity of 6 mA evoked significant decreases in OBF, followed by decreases in MAP. After severance of the ovarian sympathetic nerves, the increases in the OBF responses to low-frequency EA at 3 and 6 mA were totally abolished, and the responses at 6 mA showed a tendency to decrease, probably because of concomitant decreases in MAP. The decreased OBF and MAP responses to high-frequency EA at 6 mA remained after the ovarian sympathectomy, and the difference in the responses before and after ovarian sympathectomy was nonsignificant. In conclusion, the present study showed that low-frequency EA stimulation increases OBF as a reflex response via the ovarian sympathetic nerves, whereas high-frequency EA stimulation decreases OBF as a passive response following systemic circulatory changes.

  2. Adequate trust avails, mistaken trust matters: on the moral responsibility of doctors as proxies for patients' trust in biobank research.

    PubMed

    Johnsson, Linus; Helgesson, Gert; Hansson, Mats G; Eriksson, Stefan

    2013-11-01

    In Sweden, most patients are recruited into biobank research by non-researcher doctors. Patients' trust in doctors may therefore be important to their willingness to participate. We suggest a model of trust that makes sense of such transitions of trust between domains and distinguishes adequate trust from mistaken trust. The unique position of doctors implies, we argue, a Kantian imperfect duty to compensate for patients' mistaken trust. There are at least three kinds of mistaken trust, each of which requires a different set of countermeasures. First, trust is mistaken when necessary competence is lacking; the competence must be developed or the illusion dispelled. Second, trust is irrational whenever the patient is mistaken about his actual reasons for trusting. Care must therefore be taken to support the patient's reasoning and moral agency. Third, some patients inappropriately trust doctors to recommend only research that will benefit them directly. Such trust should be counteracted by nurturing a culture where patients expect to be asked occasionally to contribute to the common good. PMID:22681564

  3. 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.

  4. The continuum of high ovarian response: a rational approach to the management of high responder patient subgroups.

    PubMed

    Gat, Itai; Shlush, Ekaterina; Quach, Kevin; Librach, Clifford L

    2015-01-01

    Ovarian follicular responsiveness to controlled ovarian hyperstimulation (COH) with gonadotropins is extremely variable between individual patients, and even from cycle to cycle for the same patient. High responder patients are characterized by an exaggerated response to gonadotropin administration, accompanied by a higher risk for ovarian hyperstimulation syndrome (OHSS). In spite of its importance, the literature regarding high responders is characterized by heterogeneous classification methodologies. A clear separation should be drawn between risk factors for a high ovarian response and the actual response exhibited by a patient to stimulation. Similarly, it is important to distinguish between high ovarian response and development of clinically significant OHSS. In this article we: (1) review recent publications pertaining to the identification and clinical management of high responders, (2) propose an integrated clinical model to differentiate sub-groups within this population based on this review, and (3) suggest specific protocols for each sub-group. The model is based on a chronological patient assessment in an effort to target treatment based on the specific clinical circumstances. It is our hope that the algorithm we have developed will assist clinicians to supply targeted and precise treatments in order to achieve a favorable reproductive outcome with minimum complications for each patient. PMID:26516651

  5. 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.

  6. Do special constables in London feel that they are adequately prepared to meet their first aid responsibilities? A qualitative study

    PubMed Central

    Meakin, Richard

    2016-01-01

    Objective This study's aims were to explore the views of special constables in the London metropolitan police force concerning their obligations and skills as first aiders. Background The metropolitan police force provides police officers to act as first responders to emergency calls made by the public. Special constables act with the same powers and responsibility as police officers and are required to deal with incidents involving medical emergencies. Setting West London Police Station. Participants Fifteen special constables entered and completed the study. Methods and Outcome Measures A qualitative study involving semistructured interviews, participant observation, and reflective work. The outcome measures were the themes derived from the ‘thematic framework approach’ to analysis. Results Four main themes were identified. (1) ‘Our responsibility?’—Special constables felt they had a responsibility, but were unsure of the origin of this responsibility, with many feeling it stemmed from public expectation. (2) ‘Confidence’—Special constables had mixed feelings regarding their confidence in first aid scenarios and many felt that more could be done to improve their confidence. (3) ‘Training needs’—Many felt the current training system was lacking in several ways including regularity, teaching and content. (4) ‘Personal first aid knowledge’—Special constables were disappointed with their past performances. Conclusions Owing to the small size of this study, the conclusions are limited; however, if the findings are confirmed by larger studies, they suggest the need to improve the confidence of special constables in first aid situations. PMID:26826155

  7. Assessing response in breast cancer with dynamic contrast-enhanced magnetic resonance imaging: are signal intensity-time curves adequate?

    PubMed

    Woolf, David K; Padhani, Anwar R; Taylor, N Jane; Gogbashian, Andrew; Li, Sonia P; Beresford, Mark J; Ah-See, Mei-Lin; Stirling, James; Collins, David J; Makris, Andreas

    2014-09-01

    Quantitative DCE-MRI parameters including K(trans) (transfer constant min(-1)) can predict both response and outcome in breast cancer patients treated with neoadjuvant chemotherapy (NAC). Quantitative methods are time-consuming to calculate, requiring expensive software and interpretive expertise. For diagnostic purposes, signal intensity-time curves (SITCs) are used for tissue characterisation. In this study, we compare the ability of NAC-related changes in SITCs with K(trans) to predict response and outcomes. 73 women with primary breast cancer underwent DCE-MRI studies before and after two cycles of NAC. Patients received anthracycline and/or docetaxel-based chemotherapy. At completion of NAC, patients had local treatment with surgery & radiotherapy and further systemic treatments. SITCs for paired DCE-MRI studies were visually scored using a five-curve type classification schema encompassing wash-in and wash-out phases and correlated with K(trans) values and to the endpoints of pathological response, OS and DFS. 58 paired patients studies were evaluable. The median size by MRI measurement for 52 tumours was 38 mm (range 17-86 mm) at baseline and 26 mm (range 10-85 mm) after two cycles of NAC. Median baseline K(trans) (min(-1)) was 0.214 (range 0.085-0.469), and post-two cycles of NAC was 0.128 (range 0.013-0.603). SITC shapes were significantly related to K(trans) values both before (χ (2) = 43.3, P = 0.000) and after two cycles of NAC (χ (2) = 60.5, P = 0.000). Changes in curve shapes were significantly related to changes in K(trans) (χ (2) = 53.5, P = 0.000). Changes in curve shape were significantly correlated with clinical (P = 0.005) and pathological response (P = 0.005). Reductions in curve shape of ≥1 point were significant for overall improved survival using Kaplan-Meier analysis with a 5-year OS of 80.9 versus 68.6 % (P = 0.048). SITCs require no special software to generate and provide a useful method of assessing the

  8. The influence of circulating anti-Müllerian hormone on ovarian responsiveness to ovulation induction with gonadotrophins in women with polycystic ovarian syndrome: a pilot study

    PubMed Central

    2013-01-01

    Background Women with polycystic ovarian syndrome (PCOS) are known to have elevated circulating Anti-Müllerian hormone (AMH), which has been found to desensitize ovarian follicles to follicle stimulating hormone (FSH). The purpose of this study was to investigate the impact of high circulating AMH on ovarian responsiveness to ovulation induction with gonadotrophins in PCOS women. Methods This prospective observational pilot study was conducted in two collaborating Fertility Centres in the UK and Egypt. The study included 20 consecutive anovulatory women with PCOS who underwent 34 cycles of human menopausal gonadotrophin (hMG) ovarian stimulation using chronic low-dose step up protocol. Blood samples were collected for the measurement of serum AMH concentrations in the early follicular (day 2-3) phase in all cycles of hMG treatment. The serum levels of AMH were compared between cycles with good vs. poor response. The good response rates and the total dose and duration of hMG treatment were compared between cycles with high vs. low serum AMH concentrations. Results Cycles with poor response (no or delayed ovulation requiring >20 days of hMG treatment) had significantly (p = .007) higher median{range} serum AMH concentration (6.5{3.2-13.4}ng/ml) compared to that (4.0{2.2-10.2}ng/ml) of cycles with good response (ovulation within 20 days of hMG treatment). ROC curve showed AMH to be a useful predictor of poor response to hMG stimulation (AUC, 0.772; P = 0.007). Using a cut-off level of 4.7 ng/ml, AMH had a sensitivity of 100% and specificity of 58% in predicting poor response. The good response rate was significantly (p < .001) greater in cycles with lower AMH (<4.7 ng/ml) compared to that in those with AMH > = 4.7 ng/ml (100% vs. 35%, respectively). All cycles with markedly raised serum AMH levels (> 10.2 ng/ml) were associated with poor response. Cycles with high AMH (> = 4.7 ng/ml) required significantly (p < .001) greater amounts (median

  9. Molecular identification of GD3 as a suppressor of the innate immune response in ovarian cancer

    PubMed Central

    Webb, Tonya J.; Li, Xiangming; Giuntoli, Robert L.; Lopez, Pablo H.H.; Heuser, Christoph; Schnaar, Ronald L.; Tsuji, Moriya; Kurts, Christian; Oelke, Mathias; Schneck, Jonathan P.

    2012-01-01

    Tumors often display mechanisms to avoid or suppress immune recognition. One such mechanism is the shedding of gangliosides into the local tumor microenvironment, and a high concentration of circulating gangliosides is associated with poor prognosis. In this study, we identify ganglioside GD3, which was isolated from the polar lipid fraction of ovarian cancer-associated ascites, as an inhibitory factor that prevents innate immune activation of natural killer T (NKT) cells. Purified GD3 displayed a high affinity for both human and mouse CD1d, a molecule involved in the presentation of lipid antigens to T cells. Purified GD3, as well as substances within the ascites, bound to the CD1d antigenic binding site and did not require additional processing for its inhibitory effect on NKT cells. Importantly, in vivo administration of GD3 inhibited α-GalCer- induced NKT cell activation in a dose dependent manner. These data therefore indicate that ovarian cancer tumors may use GD3 to inhibit the anti-tumor NKT cell response as an early mechanism of tumor immune evasion. PMID:22649190

  10. Ovarian cancer.

    PubMed

    Matulonis, Ursula A; Sood, Anil K; Fallowfield, Lesley; Howitt, Brooke E; Sehouli, Jalid; Karlan, Beth Y

    2016-01-01

    Ovarian cancer is not a single disease and can be subdivided into at least five different histological subtypes that have different identifiable risk factors, cells of origin, molecular compositions, clinical features and treatments. Ovarian cancer is a global problem, is typically diagnosed at a late stage and has no effective screening strategy. Standard treatments for newly diagnosed cancer consist of cytoreductive surgery and platinum-based chemotherapy. In recurrent cancer, chemotherapy, anti-angiogenic agents and poly(ADP-ribose) polymerase inhibitors are used, and immunological therapies are currently being tested. High-grade serous carcinoma (HGSC) is the most commonly diagnosed form of ovarian cancer and at diagnosis is typically very responsive to platinum-based chemotherapy. However, in addition to the other histologies, HGSCs frequently relapse and become increasingly resistant to chemotherapy. Consequently, understanding the mechanisms underlying platinum resistance and finding ways to overcome them are active areas of study in ovarian cancer. Substantial progress has been made in identifying genes that are associated with a high risk of ovarian cancer (such as BRCA1 and BRCA2), as well as a precursor lesion of HGSC called serous tubal intraepithelial carcinoma, which holds promise for identifying individuals at high risk of developing the disease and for developing prevention strategies. PMID:27558151

  11. Invited commentary: a single nucleotide polymorphism in BMP15 is associated with high response to controlled ovarian hyperstimulation.

    PubMed

    Abir, Ronit; Fisch, Benjamin

    2011-07-01

    A report has been published which shows a connection between single nucleotide polymorphisms (SNP) in the bone morphogenetic protein 15 (BMP15) gene and ovarian hyperstimulation syndrome (OHSS) in women, similar to reported effects of heterozygous BMP15 point mutations in sheep. The report also describes the near-significant presence of another BMP15 gene SNP correlated with a low response to ovarian stimulation. Previous studies associated two SNP with anovulation or infertility in women with polycystic ovary syndrome, and heterozygosity for another BMP15 SNP resulted in ovarian dysgenesis and hypergonadotrophic failure. In sheep, homozygous point mutations or immunization against BMP15 led to follicular developmental arrest, ovarian dysgenesis and streak ovaries. In mammalian (including human) ovaries BMP15 and its three receptors were shown to be expressed from primary or primordial follicular stages, suggesting that BMP15 might also be involved in activating primordial follicles, and could possibly serve as a marker of follicular reserve. BMP15 also inhibited follicle stimulating hormone receptor expression, was associated with cumulus expansion and its high follicular-fluid concentration was correlated with improved oocyte and embryo quality. Thus, BMP15 seems to be an important regulator of ovarian function. Further studies are needed to clarify its roles in human female fertility.

  12. Ovarian tumor (OTU)-domain containing viral proteases evade ubiquitin- and ISG15-dependent innate immune responses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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, a...

  13. Effect of Nrf2 on rat ovarian tissues against atrazine-induced anti-oxidative response.

    PubMed

    Zhao, Fan; Li, Kun; Zhao, Lijing; Liu, Jian; Suo, Qi; Zhao, Jing; Wang, Hebin; Zhao, Shuhua

    2014-01-01

    The environmental persistence and bioaccumulation of herbicide atrazine may pose a significant threat to human health. In this experiment, Wistar rats were treated by 5, 25 and 125 mg·kg(-1) atrazine respectively for 28 days, and the oxidative stress responses as well as the activations of Nrf2 signaling pathway in ovarian tissues induced by atrazine were observed. The results showed that after be treated by atrazine, the proportion of atretic follicles in the rat ovary were increased, the contents of NO and MDA in the tissue homogenates were increased, the over-expressed Nrf2 transferred into the nuclei and played an antioxidant role by up-regulated the expression of II phase detoxifying enzymes such as HO1 and NQO1 and the expression of antioxidant enzymes such as CAT, SOD and GSH-PX.

  14. 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

  15. 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.

  16. Dietary Lipid and Cholesterol Induce Ovarian Dysfunction and Abnormal LH Response to Stimulation in Rabbits

    PubMed Central

    Dupont, Charlotte; Tarrade, Anne; Picone, Olivier; Larcher, Thibaut; Dahirel, Michèle; Poumerol, Elodie; Mandon-Pepin, Béatrice; Lévy, Rachel; Chavatte-Palmer, Pascale

    2013-01-01

    Background/Aim Excess of fat intake is dramatically increasing in women of childbearing age and results in numerous health complications, including reproductive disorders. Using rabbit does as a biomedical model, the aim of this study was to evaluate onset of puberty, endocrine responses to stimulation and ovarian follicular maturation in females fed a high fat high cholesterol diet (HH diet) from 10 weeks of age (i.e., 2 weeks before normal onset of puberty) or a control diet (C diet). Methodology/Principal Findings Three experiments were performed, each including 8 treated (HH group) and 8 control (C group) does. In experiment 1, the endocrine response to Gonadotropin releasing hormone (GnRH) was evaluated at 13, 18 and 22 weeks of age. In experiment 2, the follicular population was counted in ovaries of adult females (18 weeks of age). In experiment 3, the LH response to mating and steroid profiles throughout gestation were evaluated at 18 weeks of age. Fetal growth was monitored by ultrasound and offspring birth weight was recorded. Data showed a significantly higher Luteinizing hormone (LH) response after induction of ovulation at 13 weeks of age in the HH group. There was no difference at 18 weeks, but at 22 weeks, the LH response to GnRH was significantly reduced in the HH group. The number of atretic follicles was significantly increased and the number of antral follicles significantly reduced in HH does vs. controls. During gestation, the HH diet induced intra-uterine growth retardation (IUGR). Conclusion The HH diet administered from before puberty onwards affected onset of puberty, follicular growth, hormonal responses to breeding and GnRH stimulation in relation to age and lead to fetal IUGR. PMID:23690983

  17. 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.

  18. Canada's Compassionate Care Benefit: Is it an adequate public health response to addressing the issue of caregiver burden in end-of-life care?

    PubMed Central

    2011-01-01

    Background An increasingly significant public health issue in Canada, and elsewhere throughout the developed world, pertains to the provision of adequate palliative/end-of-life (P/EOL) care. Informal caregivers who take on the responsibility of providing P/EOL care often experience negative physical, mental, emotional, social and economic consequences. In this article, we specifically examine how Canada's Compassionate Care Benefit (CCB) - a contributory benefits social program aimed at informal P/EOL caregivers - operates as a public health response in sustaining informal caregivers providing P/EOL care, and whether or not it adequately addresses known aspects of caregiver burden that are addressed within the population health promotion (PHP) model. Methods As part of a national evaluation of Canada's Compassionate Care Benefit, 57 telephone interviews were conducted with Canadian informal P/EOL caregivers in 5 different provinces, pertaining to the strengths and weaknesses of the CCB and the general caregiving experience. Interview data was coded with Nvivo software and emerging themes were identified by the research team, with such findings published elsewhere. The purpose of the present analysis was identified after comparing the findings to the literature specific to caregiver burden and public health, after which data was analyzed using the PHP model as a guiding framework. Results Informal caregivers spoke to several of the determinants of health outlined in the PHP model that are implicated in their burden experience: gender, income and social status, working conditions, health and social services, social support network, and personal health practises and coping strategies. They recognized the need for improving the CCB to better address these determinants. Conclusions This study, from the perspective of family caregivers, demonstrates that the CCB is not living up to its full potential in sustaining informal P/EOL caregivers. Effort is required to

  19. Ovarian Cancer

    MedlinePlus

    Ovarian Cancer There are five main types of cancer that affect a woman’s reproductive organs: cervical, ovarian, uterine, ... rare fallopian tube cancer.) This fact sheet about ovarian cancer is part of the Centers for Disease Control ...

  20. 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 ...

  1. Effective treatment protocol for poor ovarian response: A systematic review and meta-analysis.

    PubMed

    Jeve, Yadava Bapurao; Bhandari, Harish Malappa

    2016-01-01

    Poor ovarian response represents an increasingly common problem. This systematic review was aimed to identify the most effective treatment protocol for poor response. We searched MEDLINE, EMBASE, and The Cochrane Library from 1980 to October 2015. Study quality assessment and meta-analyses were performed according to the Cochrane recommendations. We found 61 trials including 4997 cycles employing 10 management strategies. Most common strategy was the use of gonadotropin-releasing hormone antagonist (GnRHant), and was compared with GnRH agonist protocol (17 trials; n = 1696) for pituitary down-regulation which showed no significant difference in the outcome. Luteinizing hormone supplementation (eight trials, n = 847) showed no difference in the outcome. Growth hormone supplementation (seven trials; n = 251) showed significant improvement in clinical pregnancy rate (CPR) and live birth rate (LBR) with an odds ratio (OR) of 2.13 (95% CI 1.06-4.28) and 2.96 (95% CI 1.17-7.52). Testosterone supplementation (three trials; n = 225) significantly improved CPR (OR 2.4; 95% CI 1.16-5.04) and LBR (OR 2.18; 95% CI 1.01-4.68). Aromatase inhibitors (four trials; n = 223) and dehydroepiandrosterone supplementation (two trials; n = 57) had no effect on outcome. PMID:27382230

  2. Effective treatment protocol for poor ovarian response: A systematic review and meta-analysis.

    PubMed

    Jeve, Yadava Bapurao; Bhandari, Harish Malappa

    2016-01-01

    Poor ovarian response represents an increasingly common problem. This systematic review was aimed to identify the most effective treatment protocol for poor response. We searched MEDLINE, EMBASE, and The Cochrane Library from 1980 to October 2015. Study quality assessment and meta-analyses were performed according to the Cochrane recommendations. We found 61 trials including 4997 cycles employing 10 management strategies. Most common strategy was the use of gonadotropin-releasing hormone antagonist (GnRHant), and was compared with GnRH agonist protocol (17 trials; n = 1696) for pituitary down-regulation which showed no significant difference in the outcome. Luteinizing hormone supplementation (eight trials, n = 847) showed no difference in the outcome. Growth hormone supplementation (seven trials; n = 251) showed significant improvement in clinical pregnancy rate (CPR) and live birth rate (LBR) with an odds ratio (OR) of 2.13 (95% CI 1.06-4.28) and 2.96 (95% CI 1.17-7.52). Testosterone supplementation (three trials; n = 225) significantly improved CPR (OR 2.4; 95% CI 1.16-5.04) and LBR (OR 2.18; 95% CI 1.01-4.68). Aromatase inhibitors (four trials; n = 223) and dehydroepiandrosterone supplementation (two trials; n = 57) had no effect on outcome.

  3. Effective treatment protocol for poor ovarian response: A systematic review and meta-analysis

    PubMed Central

    Jeve, Yadava Bapurao; Bhandari, Harish Malappa

    2016-01-01

    Poor ovarian response represents an increasingly common problem. This systematic review was aimed to identify the most effective treatment protocol for poor response. We searched MEDLINE, EMBASE, and The Cochrane Library from 1980 to October 2015. Study quality assessment and meta-analyses were performed according to the Cochrane recommendations. We found 61 trials including 4997 cycles employing 10 management strategies. Most common strategy was the use of gonadotropin-releasing hormone antagonist (GnRHant), and was compared with GnRH agonist protocol (17 trials; n = 1696) for pituitary down-regulation which showed no significant difference in the outcome. Luteinizing hormone supplementation (eight trials, n = 847) showed no difference in the outcome. Growth hormone supplementation (seven trials; n = 251) showed significant improvement in clinical pregnancy rate (CPR) and live birth rate (LBR) with an odds ratio (OR) of 2.13 (95% CI 1.06–4.28) and 2.96 (95% CI 1.17–7.52). Testosterone supplementation (three trials; n = 225) significantly improved CPR (OR 2.4; 95% CI 1.16–5.04) and LBR (OR 2.18; 95% CI 1.01–4.68). Aromatase inhibitors (four trials; n = 223) and dehydroepiandrosterone supplementation (two trials; n = 57) had no effect on outcome. PMID:27382230

  4. Aberrant DNA damage response pathways may predict the outcome of platinum chemotherapy in ovarian cancer.

    PubMed

    Stefanou, Dimitra T; Bamias, Aristotelis; Episkopou, Hara; Kyrtopoulos, Soterios A; Likka, Maria; Kalampokas, Theodore; Photiou, Stylianos; Gavalas, Nikos; Sfikakis, Petros P; Dimopoulos, Meletios A; Souliotis, Vassilis L

    2015-01-01

    Ovarian carcinoma (OC) is the most lethal gynecological malignancy. Despite the advances in the treatment of OC with combinatorial regimens, including surgery and platinum-based chemotherapy, patients generally exhibit poor prognosis due to high chemotherapy resistance. Herein, we tested the hypothesis that DNA damage response (DDR) pathways are involved in resistance of OC patients to platinum chemotherapy. Selected DDR signals were evaluated in two human ovarian carcinoma cell lines, one sensitive (A2780) and one resistant (A2780/C30) to platinum treatment as well as in peripheral blood mononuclear cells (PBMCs) from OC patients, sensitive (n = 7) or resistant (n = 4) to subsequent chemotherapy. PBMCs from healthy volunteers (n = 9) were studied in parallel. DNA damage was evaluated by immunofluorescence γH2AX staining and comet assay. Higher levels of intrinsic DNA damage were found in A2780 than in A2780/C30 cells. Moreover, the intrinsic DNA damage levels were significantly higher in OC patients relative to healthy volunteers, as well as in platinum-sensitive patients relative to platinum-resistant ones (all P<0.05). Following carboplatin treatment, A2780 cells showed lower DNA repair efficiency than A2780/C30 cells. Also, following carboplatin treatment of PBMCs ex vivo, the DNA repair efficiency was significantly higher in healthy volunteers than in platinum-resistant patients and lowest in platinum-sensitive ones (t1/2 for loss of γH2AX foci: 2.7±0.5h, 8.8±1.9h and 15.4±3.2h, respectively; using comet assay, t1/2 of platinum-induced damage repair: 4.8±1.4h, 12.9±1.9h and 21.4±2.6h, respectively; all P<0.03). Additionally, the carboplatin-induced apoptosis rate was higher in A2780 than in A2780/C30 cells. In PBMCs, apoptosis rates were inversely correlated with DNA repair efficiencies of these cells, being significantly higher in platinum-sensitive than in platinum-resistant patients and lowest in healthy volunteers (all P<0.05). We conclude that

  5. Germline and Somatic Mutations in Homologous Recombination Genes Predict Platinum Response and Survival in Ovarian, Fallopian Tube, and Peritoneal Carcinomas

    PubMed Central

    Pennington, Kathryn P.; Walsh, Tom; Harrell, Maria I.; Lee, Ming K.; Pennil, Christopher C.; Rendi, Mara H.; Thornton, Anne; Norquist, Barbara M.; Casadei, Silvia; Nord, Alexander S.; Agnew, Kathy J.; Pritchard, Colin C.; Scroggins, Sheena; Garcia, Rochelle L.; King, Mary-Claire; Swisher, Elizabeth M.

    2013-01-01

    Purpose Hallmarks of germline BRCA1/2-associated ovarian carcinomas include chemosensitivity and improved survival. The therapeutic impact of somatic BRCA1/2 mutations and mutations in other homologous recombination (HR) DNA repair genes is uncertain. Experimental Design Using targeted capture and massively parallel genomic sequencing, we assessed 390 ovarian carcinomas for germline and somatic loss-of-function mutations in 30 genes, including BRCA1, BRCA2, and 11 other genes in the HR pathway. Results 31% of ovarian carcinomas had a deleterious germline (24%) and/or somatic (9%) mutation in one or more of the 13 HR genes: BRCA1, BRCA2, ATM, BARD1, BRIP1, CHEK1, CHEK2, FAM175A, MRE11A, NBN, PALB2, RAD51C, and RAD51D. Non-serous ovarian carcinomas had similar rates of HR mutations to serous carcinomas (28% vs. 31%, p=0.6), including clear cell, endometrioid, and carcinosarcoma. The presence of germline and somatic HR mutations was highly predictive of primary platinum sensitivity (p=0.0002) and improved overall survival (p=0.0006), with median overall survival 66 months in germline HR mutation carriers, 59 months in cases with a somatic HR mutation, and 41 months for cases without an HR mutation. Conclusions Germline or somatic mutations in HR genes are present in almost one-third of ovarian carcinomas, including both serous and non-serous histologies. Somatic BRCA1/2 mutations and mutations in other HR genes have a similar positive impact on overall survival and platinum responsiveness as germline BRCA1/2 mutations. The similar rate of HR mutations in non-serous carcinomas supports their inclusion in PARP inhibitor clinical trials. PMID:24240112

  6. Aberrant Alternative Polyadenylation is Responsible for Survivin Up-regulation in Ovarian Cancer

    PubMed Central

    He, Xiang-Jun; Zhang, Qi; Ma, Li-Ping; Li, Na; Chang, Xiao-Hong; Zhang, Yu-Jun

    2016-01-01

    Background: Survivin is an oncoprotein silenced in normal mature tissues but reactivated in serous ovarian cancer (SOC). Although transcriptional activation is assumed for its overexpression, the long 3'-untranslated region (3'-UTR) in survivin gene, which contains many alternate polyadenylation (APA) sites, implies a propensity for posttranscriptional control and therefore was the aim of our study. Methods: The abundance of the coding region, the proximal and the distal region of survivin mRNA 3'-UTR, was evaluated by real-time polymerase chain reaction (PCR) in SOC samples, cell lines, and normal fallopian tube (NFT) tissues. The APA sites were confirmed by rapid amplification of cDNA 3' ends and DNA sequencing. Real-time PCR were used to screen survivin-targeting microRNAs (miRNAs) that were inversely correlated with survivin. The expression of an inversely correlated miRNA was restored by pre-miRNA transfection or induction with a genotoxic agent to test its inhibitory effect on survivin overexpression. Results: Varying degrees of APA were observed in SOC by comparing the abundance of the proximal and the distal region of survivin 3'-UTR, and changes of 3'-UTR correlated significantly with survivin expression (r = 0.708, P < 0.01). The main APA sites are proved at 1197 and 1673 of survivin 3'-UTR by DNA sequencing. Higher level of 3'-UTR proximal region than coding region was observed in NFT, as well as in SOC and cell lines. Among the survivin-targeting miRNAs, only a few highly expressed miRNAs were inversely correlated with survivin levels, and they mainly targeted the distal part of the 3'-UTR. However, in ovarian cancer cells, restoration of an inversely correlated miRNA (miR-34c) showed little effect on survivin expression. Conclusions: In NFT tissues, survivin is not transcriptionally silenced but regulate posttranscriptionally. In SOC, aberrant APA leads to the shortening of survivin 3'-UTR which enables it to escape the negative regulation of mi

  7. Combined treatment of L1CAM antibodies and cytostatic drugs improve the therapeutic response of pancreatic and ovarian carcinoma.

    PubMed

    Schäfer, Heiner; Dieckmann, Chantal; Korniienko, Olena; Moldenhauer, Gerhard; Kiefel, Helena; Salnikov, Alexey; Krüger, Achim; Altevogt, Peter; Sebens, Susanne

    2012-06-01

    The adhesion molecule L1CAM (CD171) accounts for enhanced motility, invasiveness and chemoresistance of tumor cells and represents a novel marker for various tumor entities including pancreatic and ovarian carcinoma. Recently, we showed that L1CAM inhibition increases the apoptotic response of tumor cells towards cytostatic drugs pointing to the potential of L1CAM to serve as a chemosensitizer in anti-cancer therapy. Thus, the present study evaluated the therapeutic potential of combined treatment with L1CAM antibodies and chemotherapeutic drugs in pancreatic and ovarian carcinoma model systems in vivo. Two L1CAM-specific antibodies (L1-14.10 and L1-9.3/2a) exhibiting high binding affinity to the L1CAM expressing pancreatic adenocarcinoma cell line Colo357 and the ovarian carcinoma cell line SKOV3ip were used for treatment. The combined therapy of SCID mice with either L1CAM antibody and gemcitabine and paclitaxel, respectively, reduced the growth of subcutaneously grown Colo357 or SKOV3ip tumors more efficiently than treatment with the cytostatic drug alone or in combination with control IgG. This was accompanied by an increased number of apoptotic tumor cells along with an elevated procaspase-8 expression. Furthermore, a lowered activation of NF-κB along with a reduced expression of VEGF and a diminished number of CD31-positive blood vessels were observed in tumors after combined therapy compared to control treatments, while the infiltration of F4/80-positive macrophages increased. Overall, these data provide new insights into the mechanism of the anti-cancer activity of L1CAM-blocking antibodies in vivo and support the suitability of L1CAM as a target for chemosensitization and of L1CAM-interfering antibodies as an appropriate tool to increase the therapeutic response of pancreatic and ovarian carcinoma.

  8. Effect of concentrate supplementation on performance, ovarian response, and some biochemical profile of Malpura ewes.

    PubMed

    Naqvi, S M K; Soren, N M; Karim, S A

    2011-06-01

    Effect of feed flushing on ovulation rate was investigated during the autumn seasons on 24 adult Malpura ewes (BW 34.8 ± 0.58 kg and age 4-7 years) equally divided into two groups. Ewes in G1 (group 1) were grazed 8-10 h daily on Cenchrus ciliaris pasture interspersed with seasonal shrub. In addition to grazing, concentrate was provided at 1.5% of BW to the animals in G2 (group 2) for a period of 35 days. Estrus was synchronized by a double injection schedule of PGF(2α) at 0 and 10 days of the experiment and detected by parading aproned rams at 6 h intervals. Blood samples were collected at weekly interval during the estrous cycle. A rumen fermentation study was conducted on day 23 of the experiment at 0 and 4 h post-concentrate feeding. Ovarian responses in terms of number of corpora lutea and large follicles was examined on all the ewes by laparoscopy after 3 to 6 days of each estrus and were found to be similar in both the groups. Hemoglobin and packed cell volume, total protein, albumin, and globulin were similar among the groups. Concentration of plasma glucose (12 and 22 days) was higher (P < 0.05) in G2 vis-à-vis control. Plasma urea was higher (P < 0.01) in the control than G2. Rumen liquor pH, concentration of total N, TCA-ppt N, NH(3)-N, and TVFA were significantly higher (P < 0.01) in G2 than the control. Thus, it can be concluded that concentrate supplementation in ewes prior to mating (flushing) did not enhance ovulation response during the autumn season. PMID:21287364

  9. Global gene expression analysis of early response to chemotherapy treatment in ovarian cancer spheroids

    PubMed Central

    L'Espérance, Sylvain; Bachvarova, Magdalena; Tetu, Bernard; Mes-Masson, Anne-Marie; Bachvarov, Dimcho

    2008-01-01

    Background Chemotherapy (CT) resistance in ovarian cancer (OC) is broad and encompasses diverse unrelated drugs, suggesting more than one mechanism of resistance. To better understand the molecular mechanisms controlling the immediate response of OC cells to CT exposure, we have performed gene expression profiling in spheroid cultures derived from six OC cell lines (OVCAR3, SKOV3, TOV-112, TOV-21, OV-90 and TOV-155), following treatment with 10,0 μM cisplatin, 2,5 μM paclitaxel or 5,0 μM topotecan for 72 hours. Results Exposure of OC spheroids to these CT drugs resulted in differential expression of genes associated with cell growth and proliferation, cellular assembly and organization, cell death, cell cycle control and cell signaling. Genes, functionally involved in DNA repair, DNA replication and cell cycle arrest were mostly overexpressed, while genes implicated in metabolism (especially lipid metabolism), signal transduction, immune and inflammatory response, transport, transcription regulation and protein biosynthesis, were commonly suppressed following all treatments. Cisplatin and topotecan treatments triggered similar alterations in gene and pathway expression patterns, while paclitaxel action was mainly associated with induction of genes and pathways linked to cellular assembly and organization (including numerous tubulin genes), cell death and protein synthesis. The microarray data were further confirmed by pathway and network analyses. Conclusion Most alterations in gene expression were directly related to mechanisms of the cytotoxics actions in OC spheroids. However, the induction of genes linked to mechanisms of DNA replication and repair in cisplatin- and topotecan-treated OC spheroids could be associated with immediate adaptive response to treatment. Similarly, overexpression of different tubulin genes upon exposure to paclitaxel could represent an early compensatory effect to this drug action. Finally, multicellular growth conditions that are

  10. Different ovarian responses to potential mates underlie species-specific breeding strategies in common marmoset and Goeldi's monkey.

    PubMed

    Mattle, Franziska M E; Pryce, Christopher R; Anzenberger, Gustl

    2008-08-01

    Callitrichids are cooperative breeders, characterized by obligate twinning, extensive paternal care, and monopolization of reproduction by the dominant female. This is the case in the common marmoset, and in common marmoset groups of more than one adult female, subordinate females are typically acyclic consistent with infertility. However, one callitrichid, Goeldi's monkey, gives birth to singletons and exhibits low paternal care. Given these reproductive traits of Goeldi's monkey, we hypothesized that there would not be suppression of ovarian activity. To test this hypothesis, we applied non-invasive endocrine methods in a step-wise experiment with laboratory groups of both species. In each species, six pairs of sisters were studied alone, in visual contact with an unrelated male and in a polygynous trio with the male, and urine samples were collected for determination of oestrogen titres reflecting ovarian activity. Common marmoset sister pairs exhibited a marked difference in social status: during the study 5 of 6 dominant females conceived but only 1 of 6 subordinate females; the remaining 5 subordinates were acyclic at the end of the study, and instances of ovulation typically resulted in aggression. Goeldi's monkey sister pairs showed no status differences: in all pairs, however, both sisters exhibited a temporary cessation of ovarian cyclicity on trio formation, followed by ovulation and conception. We conclude that these marked differences in ovarian responses reflect the differences in inter-female competition for paternal caregiving resources. In common marmosets with high inter-female competition, suppression of ovulation functions to reduce aggression received by subordinate females; in Goeldi's monkey with low competition, temporary cessation of ovulation could facilitate female choice.

  11. pH-Responsive Polymer Conjugate of Pirarubicin With Styrene Maleic Acid Copolymer as a Potential Therapeutic for Ovarian Cancer.

    PubMed

    Liu, Lifeng; Sun, Jinghua; Yin, Hongzhuan; Fang, Jun; Jin, Xianyu

    2016-05-01

    Previous studies indicated the potential of styrene maleic acid copolymer (SMA)-conjugated pirarubicin (4'-O-tetrahydropyranyldoxorubicin [THP]) for targeted anticancer therapy based on the enhanced permeability and retention effect. In this study, to achieve further improved therapeutic efficacy, a pH-responsive SMA-conjugated THP-containing hydrazone bond (SMA-hyd-THP) was synthesized and evaluated in vitro and ex vivo using human ovarian cancer cells and tissues. SMA-hyd-THP showed good water solubility, forming micelles with a mean particle size of 48.0 nm, which is applicable for enhanced permeability and retention-based tumor accumulation. The THP loading in this preparation was 15% (wt/wt), and release rate of free THP from SMA-hyd-THP at physiological pH (7.4) was approximately 10% in 72 h. However, it increased rapidly at pH 6.5 (42%) and 5.5 (83%), which indicates that tumor environment of weak acidic condition (pH 6.5-6.9) is favorable for release of THP. This notion was partly proved by incubating SMA-hyd-THP with tumor tissues from ovarian cancer patients. In addition, release of THP was not affected by serum, suggesting that SMA-hyd-THP is relatively stable in circulation. Finally, SMA-hyd-THP showed much increased cytotoxicity against various ovarian cancer cells at acidic tumor pH (6.5). These findings may provide an option for targeted therapy against ovarian cancer. PMID:27020984

  12. Augmentation of Response to Chemotherapy by microRNA-506 Through Regulation of RAD51 in Serous Ovarian Cancers

    PubMed Central

    Liu, Guoyan; Yang, Da; Rupaimoole, Rajesha; Pecot, Chad V.; Sun, Yan; Mangala, Lingegowda S.; Li, Xia; Ji, Ping; Cogdell, David; Hu, Limei; Wang, Yingmei; Rodriguez-Aguayo, Cristian; Lopez-Berestein, Gabriel; Shmulevich, Ilya; De Cecco, Loris; Chen, Kexin; Mezzanzanica, Delia; Xue, Fengxia; Sood, Anil K.

    2015-01-01

    Background: Chemoresistance is a major challenge in cancer treatment. miR-506 is a potent inhibitor of the epithelial-to-mesenchymal transition (EMT), which is also associated with chemoresistance. We characterized the role of miR-506 in chemotherapy response in high-grade serous ovarian cancers. Methods: We used Kaplan-Meier and log-rank methods to analyze the relationship between miR-506 and progression-free and overall survival in The Cancer Genome Atlas (TCGA) (n = 468) and Bagnoli (n = 130) datasets, in vitro experiments to study whether miR-506 is associated with homologous recombination, and response to chemotherapy agents. We used an orthotopic ovarian cancer mouse model (n = 10 per group) to test the effect of miR-506 on cisplatin and PARP inhibitor sensitivity. All statistical tests were two-sided. Results: MiR-506 was associated with better response to therapy and longer progression-free and overall survival in two independent epithelial ovarian cancer patient cohorts (PFS: high vs low miR-506 expression; Bagnoli: hazard ratio [HR] = 3.06, 95% confidence interval [CI] = 1.90 to 4.70, P < .0001; TCGA: HR = 1.49, 95% CI = 1.00 to 2.25, P = 0.04). MiR-506 sensitized cells to DNA damage through directly targeting the double-strand DNA damage repair gene RAD51. Systemic delivery of miR-506 in 8–12 week old female athymic nude mice statistically significantly augmented the cisplatin and olaparib response (mean tumor weight ± SD, control miRNA plus cisplatin vs miR-506 plus cisplatin: 0.36±0.05g vs 0.07±0.02g, P < .001; control miRNA plus olaparib vs miR-506 plus olaparib: 0.32±0.13g vs 0.05±0.02g, P = .045, respectively), thus recapitulating the clinical observation. Conclusions: MiR-506 is a robust clinical marker for chemotherapy response and survival in serous ovarian cancers and has important therapeutic value in sensitizing cancer cells to chemotherapy. PMID:25995442

  13. CXCR2 Inhibition Combined with Sorafenib Improved Antitumor and Antiangiogenic Response in Preclinical Models of Ovarian Cancer.

    PubMed

    Devapatla, Bharat; Sharma, Ankur; Woo, Sukyung

    2015-01-01

    Antiangiogenic therapy is important for the treatment of gynecological cancer. However, the therapeutic benefit derived from these treatments is transient, predominantly due to the selective activation of compensatory proangiogenic pathways that lead to rapid development of resistance. We aimed to identify and target potential alternative signaling to anti-vascular endothelial growth factor (VEGF) therapy, with a view toward developing a combination of antiangiogenic agents to provide extended therapeutic benefits. We developed a preclinical in vivo phenotypic resistance model of ovarian cancer resistant to antiangiogenic therapy. We measured dynamic changes in secreted chemokines and angiogenic signaling in tumors and plasma in response to anti-VEGF treatment, as tumors advanced from the initial responsive phase to progressive disease. In tumors that progressed following sorafenib treatment, gene and protein expression levels of proangiogenic CXC chemokines and their receptors were significantly elevated, compared with responsive tumors. The chemokine (C-X-C motif) ligand 8 (CXCL8), also known as interleukin-8 (IL-8) increase was time-dependent and coincided with the dynamics of tumor progression. We used SB225002, a pharmacological inhibitor of chemokine (C-X-C motif) receptor 2 (CXCR2), to disrupt the CXC chemokine-mediated functions of ovarian cancer cells in in vitro assays of cell growth inhibition, spheroid formation, and cell migration. The combination of CXCR2 inhibitor with sorafenib led to a synergistic inhibition of cell growth in vitro, and further stabilized tumor progression following sorafenib in vivo. Our results suggest that CXCR2-mediated chemokines may represent an important compensatory pathway that promotes resistance to antiangiogenic therapy in ovarian cancer. Thus, simultaneous blockage of this proangiogenic cytokine pathway using CXCR2 inhibitors and the VEGF receptor (VEGFR) pathway could improve the outcomes of antiangiogenic therapy

  14. CXCR2 Inhibition Combined with Sorafenib Improved Antitumor and Antiangiogenic Response in Preclinical Models of Ovarian Cancer

    PubMed Central

    Devapatla, Bharat; Sharma, Ankur; Woo, Sukyung

    2015-01-01

    Antiangiogenic therapy is important for the treatment of gynecological cancer. However, the therapeutic benefit derived from these treatments is transient, predominantly due to the selective activation of compensatory proangiogenic pathways that lead to rapid development of resistance. We aimed to identify and target potential alternative signaling to anti-vascular endothelial growth factor (VEGF) therapy, with a view toward developing a combination of antiangiogenic agents to provide extended therapeutic benefits. We developed a preclinical in vivo phenotypic resistance model of ovarian cancer resistant to antiangiogenic therapy. We measured dynamic changes in secreted chemokines and angiogenic signaling in tumors and plasma in response to anti-VEGF treatment, as tumors advanced from the initial responsive phase to progressive disease. In tumors that progressed following sorafenib treatment, gene and protein expression levels of proangiogenic CXC chemokines and their receptors were significantly elevated, compared with responsive tumors. The chemokine (C-X-C motif) ligand 8 (CXCL8), also known as interleukin-8 (IL-8) increase was time-dependent and coincided with the dynamics of tumor progression. We used SB225002, a pharmacological inhibitor of chemokine (C-X-C motif) receptor 2 (CXCR2), to disrupt the CXC chemokine-mediated functions of ovarian cancer cells in in vitro assays of cell growth inhibition, spheroid formation, and cell migration. The combination of CXCR2 inhibitor with sorafenib led to a synergistic inhibition of cell growth in vitro, and further stabilized tumor progression following sorafenib in vivo. Our results suggest that CXCR2-mediated chemokines may represent an important compensatory pathway that promotes resistance to antiangiogenic therapy in ovarian cancer. Thus, simultaneous blockage of this proangiogenic cytokine pathway using CXCR2 inhibitors and the VEGF receptor (VEGFR) pathway could improve the outcomes of antiangiogenic therapy

  15. 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

  16. 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

  17. Molecular correlates of platinum response in human high-grade serous ovarian cancer patient-derived xenografts

    PubMed Central

    Topp, M; Hartley, L; Cook, M; Heong, V; Boehm, E; McShane, L; Pyman, J; McNally, O; Ananda, S; Harrell, M; Etemadmoghadam, D; Galletta, L; Alsop, K; Mitchell, G; Fox, SB; Kerr, JB; Hutt, KJ; Kaufmann, SH; Swisher, EM; Bowtell, DD; Wakefield, M; Scott, CL

    2015-01-01

    Introduction Improvement in the ability to target underlying drivers and vulnerabilities of high-grade serous ovarian cancer (HG-SOC) requires the development of molecularly annotated pre-clinical models reflective of clinical responses. Methods We generated patient-derived xenografts (PDXs) from consecutive, chemotherapy-naïve, human HG-SOC by transplanting fresh human HG-SOC fragments into subcutaneous and intra-ovarian bursal sites of NOD/SCID IL2Rγnull recipient mice, completed molecular annotation and assessed platinum sensitivity. Results The success rate of xenografting was 83%. Of ten HG-SOC PDXs, all contained mutations in TP53, two were mutated for BRCA1, three for BRCA2, and in two, BRCA1 was methylated. In vivo cisplatin response, determined as platinum sensitive (progression-free interval ≥100 d, n=4), resistant (progression-free interval <100 d, n=3) or refractory (n=3), was largely consistent with patient outcome. Three of four platinum sensitive HG-SOC PDXs contained DNA repair gene mutations, and the fourth was methylated for BRCA1. In contrast, all three platinum refractory PDXs overexpressed dominant oncogenes (CCNE1, LIN28B and/or BCL2). Conclusions Because PDX platinum response reflected clinical outcome, these annotated PDXs will provide a unique model system for preclinical testing of novel therapies for HG-SOC. PMID:24560445

  18. Ovarian cysts

    MedlinePlus

    ... Functional ovarian cysts are not the same as ovarian tumors, or cysts due to hormone-related conditions such ... Philadelphia, PA: Elsevier; 2016:chap 17. Katz VL. Benign gynecologic lesions. In: Lentz GM, Lobo RA, Gershenson ...

  19. 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.

  20. 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 ...

  1. Elevated Peritoneal Fluid TNF-α Incites Ovarian Early Growth Response Factor 1 Expression and Downstream Protease Mediators

    PubMed Central

    Birt, Julie A.; Nabli, Henda; Stilley, Julie A.; Windham, Emma A.; Frazier, Shellaine R.

    2013-01-01

    Endometriosis-associated infertility manifests itself via multiple, poorly understood mechanisms. Our goal was to characterize signaling pathways, between peritoneal endometriotic lesions and the ovary, leading to failed ovulation. Genome-wide microarray analysis comparing ovarian tissue from an in vivo endometriosis model in the rat (Endo) with controls (Sham) identified 22 differentially expressed genes, including transiently expressed early growth response factor 1 (Egr1). The Egr1 regulates gene requisites for ovulation. The Egr1 promoter is responsive to tumor necrosis factor-alpha (TNF-α) signaling. We hypothesized that altered expression of ovarian EGR1 is induced by elevated peritoneal fluid TNF-α which is upregulated by the presence of peritoneal endometriosis. Endo rats, compared to controls, had more peritoneal fluid TNF-α and quantitative, spatial differences in Egr1 mRNA and EGR1 protein localization in follicular compartments. Interactions between elevated peritoneal fluid TNF-α and overexpression of follicular Egr1/EGR1 expression may affect downstream protease pathways impeding ovulation in endometriosis. Preliminary studies identified similar patterns of EGR1 protein localization in human ovaries from women with endometriosis and compared to those without endometriosis. PMID:23427178

  2. 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.

  3. 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. PMID:9261877

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

    PubMed

    Tumbarello, David A; 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

  5. 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. PMID:26311247

  6. 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

  7. Effect of anordiol on ovarian hormone secretion, ovulation, and uterine and vaginal responses in the immature rat.

    PubMed

    Lu, Y C; Chatterton, R T

    1994-06-01

    The purpose of this investigation was to determine the estrogenic and antiestrogenic activities of the potential contraceptive agent anordiol in the immature rat. A dose of 2.45 mumol of anordiol (AD), estradiol (E2), clomiphene citrate (CC), tamoxifen (TA), or the vehicle alone was administered to rats on the 25th and 29th days of age. Serum hormones were measured between 16:00 and 17:00 on days 30, 31, and 32; organ weights were determined on day 32. Anordiol and estradiol treatments significantly increased ovarian and uterine weight and serum LH concentrations, but CC and TA had no effect on these parameters. Vaginal cornification occurred before day 32 in all rats receiving anordiol or estradiol and in 3/5 and 4/5 rats receiving CC and TA, respectively, but not in control rats. Based on serum progesterone levels, ovulation was induced only in rats receiving anordiol or estradiol. All of the compounds tested significantly increased serum testosterone above levels in control animals, but both AD and E2 induced ovulation without a further increase in serum testosterone. We conclude that in the immature rat anordiol produces estrogenic responses in the vagina, uterus and in the hypothalamic-pituitary-ovarian axis, whereas TA and CC are estrogenic only on the vaginal and uterine epithelium.

  8. 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.

  9. Superovulatory ovarian response in Mangalica gilts is not influenced by feeding level.

    PubMed

    Egerszegi, I; Hazeleger, W; Rátky, J; Sarlós, P; Kemp, B; Bouwman, E; Solti, L; Brüssow, K-P

    2007-08-01

    The aim of the study was to compare how different feeding levels affect the ovarian potential of follicular development and oocyte maturation in response to superovulatory treatment in native Mangalica (M, n = 17) compared with Landrace (L, n = 20) pigs. Gilts of both breeds were fed high-energy (HI-2.5 kg) or low-energy (LO - 1.25 kg) feed during oestrus synchronization (15 days of Regumate feeding) till the time of oocyte aspiration (Day 6 after Regumate). Follicular growth was stimulated by the administration of 1000 IU equiue choriou gonadotropiu (eCG) 24 h after Regumate treatment, and ovulation was induced by injection of 750 IU human choriou gonadotropiu (hCG) 80 h after eCG administration. Ultrasound (US) investigation was done three times (4-10 h before, and 40-44 and 72-74 h after eCG administration) for the observation of follicular development. Oocyte and follicular fluid (FF) were collected endoscopically 34 h after hCG injection. Cumulus-oocyte complexes were evaluated, their morphology determined, and thereafter fixed and stained for chromatin evaluation. Oocytes were classified as meiosis-resumed (germinal vesicle breakdown, diakinesis, metaphase I to anaphase I) or matured (telophase I and metaphase II). FF concentrations of oestradiol and progesterone were measured by validated radioimmunoassays. In L gilts, differences were observed between HI and LO in the number of preovulatory follicles (32.3 +/- 10.5 vs 17.1 +/- 12.3, p < 0.05), but not in M (25.3 +/- 2.9 vs 28.8 +/- 7.3, p > 0.05). Initial follicular growth was not affected by feeding levels; however, preovulatory follicle size was larger in M (7.1 +/- 0.9 and 6.9 +/- 1.1 mm vs 5.7 +/- 0.7 and 5.5 +/- 0.8 mm; p < 0.05). No differences were obtained with relation to mature chromatin configuration in both breeds (L gilts: HI - 70% and LO-67% vs M gilts: HI - 67% and LO - 63%). A twofold higher oestradiol concentration was detected in FF of HI-M and LO-M (29.6 +/- 6.8 and 30.9 +/- 10.3 ng

  10. Maternal obesity is associated with ovarian inflammation and upregulation of early growth response factor 1.

    PubMed

    Ruebel, Meghan; Shankar, Kartik; Gaddy, Dana; Lindsey, Forrest; Badger, Thomas; Andres, Aline

    2016-07-01

    Obesity impairs reproductive functions through multiple mechanisms, possibly through disruption of ovarian function. We hypothesized that increased adiposity will lead to a proinflammatory gene signature and upregulation of Egr-1 protein in ovaries from obese (OB; n = 7) compared with lean (LN; n = 10) female Sprague-Dawley rats during the peri-implantation period at 4.5 days postcoitus (dpc). Obesity was induced by overfeeding (40% excess calories for 28 days) via total enteral nutrition prior to mating. OB dams had higher body weight (P < 0.001), greater fat mass (P < 0.001), and reduced lean mass (P < 0.05) and developed metabolic dysfunction with elevated serum lipids, insulin, leptin, and CCL2 (P < 0.05) compared with LN dams. Microarray analyses identified 284 differentially expressed genes between ovaries from LN vs. OB dams (±1.3 fold, P < 0.05). RT-qPCR confirmed a decrease in expression of glucose transporters GLUT4 and GLUT9 and elevation of proinflammatory genes, including CCL2, CXCL10, CXCL11, CCR2, CXCR1, and TNFα in ovaries from OB compared with LN (P < 0.05). Protein levels of PI3K and phosphorylated Akt were significantly decreased (P < 0.05), whereas nuclear levels of Egr-1 (P < 0.05) were increased in OB compared with LN ovaries. Moreover, Egr-1 was localized to granulosa cells, with the highest expression in cumulus cells of preovulatory follicles. mRNA expression of VCAN, AURKB, and PLAT (P < 0.05) correlated with %visceral fat weight (r = 0.51, -0.77, and -0.57, respectively, P ≤ 0.05), suggesting alterations in ovarian function with obesity. In summary, maternal obesity led to an upregulation of inflammatory genes and Egr-1 expression in peri-implantation ovarian tissue and a concurrent downregulation of GLUTs and Akt and PI3K protein levels. PMID:27279249

  11. 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

  12. Concentrations of steroid hormones, estrous, ovarian and reproductive responses in sheep estrous synchronized with different prostaglandin-based protocols.

    PubMed

    Fierro, S; Viñoles, C; Olivera-Muzante, J

    2016-04-01

    To determine estrous, ovarian and reproductive responses after different prostaglandin (PG)-based protocols, ewes were assigned to groups PG10, PG12, PG14 or PG16 (twoPG injections administered 10, 12, 14 or 16 days apart; respectively). Experiment I (n=132) was conducted to evaluate the estrous response, ovulation rate (OR), conception and fertility. Experiment II (n=24) was conducted to evaluate ovarian follicle growth, steroid concentrations and the interval from the second PG injection to estrus (PG-estrus) and ovulation (PG-ovulation). Estrous response was less with the PG16 (P<0.05) treatment, and the extent of estrous synchrony was greater with the PG10 and PG12 treatments. Ovarian follicle growth and the intervals for the variables PG-estrus, PG-ovulation and OR were similar among groups (P>0.05). From 8 to 4 days before estrus, progesterone (P4) concentrations were greater for the PG14 and PG16 than for the PG10 and PG12 (P<0.05) groups. There were more days where concentrations of P4 were above 3.18 nmol/L with the PG14 and PG16 than PG10 and PG12 (P<0.05) treatments. Use of the PG14 and PG16 treatments resulted in greater estradiol (E2) at estrus and 12h later than use of the PG10 and PG12 treatments. A positive correlation was observed between the duration of the luteal phase and maximum E2 concentrations, and between duration of the luteal phase and days with E2 concentrations above 10 pmol/L. Conception and fertility were greater with use of the PG14 compared with PG10 and PG12 (P<0.05) treatments. The administration of two PG injections 10, 12, 14 or 16 days apart resulted in different durations of the luteal phase that were positively associated with E2 concentrations and the reproductive outcome. The shorter luteal phases were associated with greater synchrony in time of estrus. The intervals for the variables PG-estrus, PG-ovulation and OR were similar among groups. PMID:26907940

  13. 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

  14. Characterization of the ovarian and reproductive abnormalities in prepubertal and adult estrogen non-responsive estrogen receptor alpha knock-in (ENERKI) mice.

    PubMed

    Sinkevicius, K W; Woloszyn, K; Laine, M; Jackson, K S; Greene, G L; Woodruff, T K; Burdette, J E

    2009-11-01

    Estrogen non-responsive estrogen receptor alpha (ERalpha) knock-in (ENERKI) mice have a mutation (glycine 525 to leucine, G525L) in the ligand-binding domain of ERalpha. The mutant ERalpha protein has a significantly lower affinity and response to endogenous estrogens, while not altering growth factor activated ligand-independent pathways. ENERKI females demonstrated signs of early follicle development as determined by a significant increase in antral follicle formation by 20 days of age. Adult ENERKI females were infertile, had hemorrhagic ovarian follicular cysts, and failed to develop corpora lutea in response to a superovulation regimen. These results illustrate the importance of ERalpha ligand-induced signaling for ovarian development and for estrogen feedback on the hypothalamus and pituitary. Although ERalpha ligand-induced signaling by endogenous estrogens is lost in ENERKI females, the ERalpha selective agonist propyl pyrazole triol (PPT), a synthetic nonsteroidal compound, is still able to activate G525L ERalphain vivo to increase uterine weight. To test whether PPT could restore ligand-dependent receptor activation, ENERKI females were treated with PPT and evaluated for spontaneous ovulation, ovarian hemorrhagic cysts, and LH serum levels. Daily PPT treatments beginning on day 4 of life prevented formation of ovarian hemorrhagic cysts in adult ENERKI animals. In accordance with this result, preputial gland weight and LH levels were also lowered in these animals, indicating PPT treatments most likely led to restoration of ERalpha negative feedback of the hypothalamic-pituitary axis.

  15. Effect of Varying the Energy Density of Protein-adequate Diets on Nutrient Metabolism, Clinical Chemistry, Immune Response and Growth of Muzaffarnagari Lambs

    PubMed Central

    Singh, V. K.; Pattanaik, A. K.; Goswami, T. K.; Sharma, K.

    2013-01-01

    Effects of varied dietary energy densities on immune response and performance of Muzzafarnagari lambs were ascertained in a 180-d study. Animals (n = 24), in three groups, were fed diets providing 100% (100E), 80% (80E) or 70% (70E) of their metabolizable energy requirement. Mean nutrient digestibilities varied significantly among treatments. Nitrogen intake was lower (p<0.01) in the 70E. Nitrogen retention, was reduced (p<0.001) in 80E and 70E vs 100E. The average daily gain (p<0.001) was 47.01±4.23, 13.54±1.72 and -16.67±8.24 g for 100E, 80E and 70E, respectively. Hemoglobin concentration, haematocrit, total and differential leukocyte counts were lower (p<0.001) for 80E and 70E than for 100E with a similar trend (p<0.05) for serum glucose and total protein. Serum cortisol was reduced (p<0.001) with decreased energy availability. Antibody titre to Brucella abortus S19 showed an initial reduction in 80E and 70E vs 100E. Delayed-type hypersensitivity response was lower (p<0.001) in 80E and 70E vs 100E, accompanying a lower (p<0.001) nitric oxide production by the peripheral lymphocytes. It is concluded that the reduced dietary energy density significantly affects the growth performance and immune response of lambs. PMID:25049889

  16. 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

  17. Treatment of advanced ovarian cancer with surgery, chemotherapy, and consolidation of response by whole-abdominal radiotherapy.

    PubMed

    Goldhirsch, A; Greiner, R; Dreher, E; Sessa, C; Krauer, F; Forni, M; Jungi, F W; Brunner, K W; Veraguth, P; Engeler, V

    1988-07-01

    Between April 1981 and June 1985, 195 patients with ovarian cancer, International Federation of Gynecology and Obstetrics (FIGO) Stages IIB, IIC, III, and IV, entered a trial that consisted of surgery and chemotherapy with cisplatin (P) and melphalan (PAM) with or without hexamethylmelamine (HexaPAMP or PAMP regimens) every 4 weeks for 6 cycles. Because the intent was to study the outcome by treatment after evaluation of first-line chemotherapy, patients were evaluable only if the response was assessed by a second-look operation or if measurable disease progression was documented. One hundred fifty-eight patients (81%) were evaluable for response. Forty-five (28%) achieved pathologically confirmed complete remissions (pCR), and 24 of these patients received whole-abdominal radiation (WAR) for consolidation of response. Five patients with complete remission after WAR relapsed, as did nine of the 21 with complete remission who had not undergone WAR. The 3-year time to progression percentage (TTP +/- SE) from second-look operation was 70% +/- 7% for all patients who achieved pCR, 83% +/- 8% for those who received WAR, and 49% +/- 15% for those who did not receive WAR (this was not a randomized comparison). The 3-year TTP percentage for the 49 partial responders was 21% +/- 6%, identical for the 19 who had WAR and the 30 who had no radiation therapy. Additional or alternative methods for consolidation of pCR are needed since patients continue to relapse despite optimal initial response to therapy.

  18. Ovarian Cysts

    MedlinePlus

    ... or if the cyst does not go away. Birth control pills can help prevent new cysts. A health problem that may involve ovarian cysts is polycystic ovary syndrome (PCOS). Women with PCOS can have high levels of male hormones, irregular or no periods and small ovarian ...

  19. Improvement of ovarian response and oocyte quality of aged female by administration of bone morphogenetic protein-6 in a mouse model

    PubMed Central

    2012-01-01

    Background Advancing female age remains a difficult problem in infertility treatment. Ovarian angiogenesis plays an important role in follicular development and the activation of ovarian angiogenesis has been emerged as a new strategy for the improvement of age-related decline of oocyte quality. BMP-6 affect gonadotropin signals in granulosa cells and it promotes normal fertility by enabling appropriate response to LH and normal oocyte quality. BMP-6 has a potential role in regulation of angiogenesis and regulates the expression of inhibitor of DNA-binding proteins (Ids). Ids involved in the control and timing of follicle selection and granulosa cells differentiation. Especially, Id-1 is well-characterized target of BMP-6 signaling. Therefore, this study investigated whether co-administration of BMP-6 during superovulation process improves ovarian response, oocyte quality and expression of Id-1 and vascular endothelial growth factor (VEGF) in the ovary of aged female using a mouse model. Methods Aged C57BL/6 female mice (26–31 weeks old) were superovulated by injection with 0.1 mL of 5 IU equine chorionic gonadotropin (eCG) containing recombinant mouse BMP-6 at various doses (0, 0.01, 0.1, 1, and 10 ng), followed by injection with 5 IU human chorionic gonadotropin (hCG) 48 h later. Then, the mice were immediately paired with an individual male. The aged control group was superovulated without BMP-6. Young mice of 6–9 weeks old were superovulated without BMP-6 as a positive control for superovulation and in vitro culture of embryos. Eighteen hours after hCG injection, zygotes were retrieved and cultured for 4 days. Both ovaries of each mouse were provided in the examination of ovarian expression of Id-1 and VEGF by reverse transcriptase-polymerase chain reaction, western blot, and immunohistochemistry. Results Administration of 0.1 ng BMP-6 significantly increased the number and blastocyst formation rate of oocytes ovulated and ovarian expression of Id-1 and

  20. Ovarian Cancer: In Search of Better Marker Systems Based on DNA Repair Defects

    PubMed Central

    Varga, Dominic; Deniz, Miriam; Schwentner, Lukas; Wiesmüller, Lisa

    2013-01-01

    Ovarian cancer is the fifth most common female cancer in the Western world, and the deadliest gynecological malignancy. The overall poor prognosis for ovarian cancer patients is a consequence of aggressive biological behavior and a lack of adequate diagnostic tools for early detection. In fact, approximately 70% of all patients with epithelial ovarian cancer are diagnosed at advanced tumor stages. These facts highlight a significant clinical need for reliable and accurate detection methods for ovarian cancer, especially for patients at high risk. Because CA125 has not achieved satisfactory sensitivity and specificity in detecting ovarian cancer, numerous efforts, including those based on single and combined molecule detection and “omics” approaches, have been made to identify new biomarkers. Intriguingly, more than 10% of all ovarian cancer cases are of familial origin. BRCA1 and BRCA2 germline mutations are the most common genetic defects underlying hereditary ovarian cancer, which is why ovarian cancer risk assessment in developed countries, aside from pedigree analysis, relies on genetic testing of BRCA1 and BRCA2. Because not only BRCA1 and BRCA2 but also other susceptibility genes are tightly linked with ovarian cancer-specific DNA repair defects, another possible approach for defining susceptibility might be patient cell-based functional testing, a concept for which support came from a recent case-control study. This principle would be applicable to risk assessment and the prediction of responsiveness to conventional regimens involving platinum-based drugs and targeted therapies involving poly (ADP-ribose) polymerase (PARP) inhibitors. PMID:23344037

  1. A chemotherapy response classifier based on support vector machines for high-grade serous ovarian carcinoma

    PubMed Central

    Zhou, Bo; Guo, En-Song; Yang, Zong-Yuan; Liao, Jing; Ding, Dong; Xu, Qin; Lu, Hao; Meng, Li; Wang, Shi-Xuan; Zhou, Jian-Feng; Xing, Hui; Weng, Dan-Hui; Ma, Ding; Chen, Gang

    2016-01-01

    Long-term outcome of high-grade serous epithelial ovarian carcinoma (HGSOC) remains poor as a result of recurrence and the emergence of drug resistance. Almost all the patients were given the same platinum-based chemotherapy after debulking surgery even though some of them are naturally resistant to the first-line chemotherapy. No method could verify this part of patients right after the surgery currently. In this study, we used 156 paraffin-embedded high-grade HGSOC specimens for immunohistochemical analysis with 37 immunology markers, and association between the expression levels of these markers and the chemoresponse were evaluated. A support vector machine (SVM)-based HGSOC prognostic classifier was then established, and was validated by a 95-patient independent cohort. The classifier was strongly predictive of chemotherapy resistance, and divided patients into low- and high-risk groups with significant differences progression-free survival (PFS) and overall survival (OS). This classifier may provide a potential way to predict the chemotherapy resistance of HGSOC right after the surgery, and then allow clinicians to make optimal clinical decision for those potentially chemoresistant patients. The potential clinical application of this classifier will benefit those patients with primary drug resistance. PMID:26675546

  2. Ovarian blood flow responses to electroacupuncture stimulation depend on estrous cycle and on site and frequency of stimulation in anesthetized rats.

    PubMed

    Stener-Victorin, Elisabet; Fujisawa, Shigeko; Kurosawa, Mieko

    2006-07-01

    Electroacupuncture (EA) applied to the abdomen and hindlimb modulates the ovarian blood flow (OBF) response. The present study aimed to further elucidate the role of the site and the frequency of short-term EA stimulation and the influence of the estrous cycle on the OBF response using anesthetized rats. EA stimulation was applied to the abdominal or the hindlimb muscles at three different frequencies (2, 10, and 80 Hz) during the estrus or diestrus phase. Involvement of spinal and supraspinal reflexes in OBF responses to EA stimulation was investigated by spinal cord transection. Abdominal EA stimulation at 10 Hz increased the OBF response, whereas hindlimb EA stimulation at 10 Hz and abdominal and hindlimb stimulation at 80 Hz decreased the OBF response; 2-Hz EA caused no OBF response. The OBF response to abdominal EA was more pronounced in the estrus than the diestrus phase. The OBF response to abdominal and hindlimb EA stimulation at both 10 and 80 Hz was almost abolished, both after severance of the sympathetic nerves and after spinal cord transection. In conclusion, the OBF response to both abdominal and hindlimb EA stimulation was mediated as a reflex response via the ovarian sympathetic nerves, and the response was controlled via supraspinal pathways. Furthermore, the OBF response to segmental abdominal EA stimulation was frequency dependent and amplified in the estrous phase.

  3. Epidermal growth factor, oestrogen and progesterone receptor expression in primary ovarian cancer: correlation with clinical outcome and response to chemotherapy.

    PubMed Central

    Scambia, G.; Benedetti-Panici, P.; Ferrandina, G.; Distefano, M.; Salerno, G.; Romanini, M. E.; Fagotti, A.; Mancuso, S.

    1995-01-01

    The expression of epidermal growth factor receptor (EGFR), oestrogen receptor (ER) and progesterone receptor (PR) was assayed by a radioreceptor method in 117 primary ovarian cancers. EGFR was not significantly related to any of the clinicopathological parameters examined. In patients with stage II-IV disease who underwent second-look surgery after primary chemotherapy, a significant correlation between high EGFR levels and poor response to chemotherapy was demonstrated (P = 0.031). Moreover, post-operative residual tumour showed an independent role in predicting chemotherapy response (P = 0.0007) and EGFR status showed a borderline significance (P = 0.052) in the multivariate analysis. No correlation between steroid hormone receptors and clinicopathological parameters was observed. Whereas a significant relationship was shown between EGFR positivity and a shorter overall survival (OS) (P = 0.0022) and progression-free survival (PFS) (P = 0.0033), patient survival was not related to steroid hormone receptor status. Among the parameters tested only stage, ascites and EGFR status retained an independent prognostic value in the multivariate analysis. PMID:7640219

  4. Serum anti-Müllerian hormone levels as a predictor of the ovarian response and IVF outcomes

    PubMed Central

    Choi, Min Hye; Yoo, Ji Hee; Cha, Sun Hwa; Park, Chan Woo; Yang, Kwang Moon; Song, In Ok; Koong, Mi Kyoung; Kang, Inn Soo

    2011-01-01

    Objective The aim of this study was to investigate whether anti-Mullerian hormone (AMH) levels could be predict ovarian poor/hyper response and IVF cycle outcome. Methods Between May 2010 and January 2011, serum AMH levels were evaluated with retrospective analysis. Three hundred seventy infertile women undergoing 461 IVF cycles between the ages of 20 and 42 were studied. We defined the poor response as the number of oocytes retrieved was equal or less than 3, and the hyper response as more than 25 oocytes retrieved. Serum AMH was measured by commercial enzyme-linked immunoassay. Results The number of oocytes retrieved was more correlated with the serum AMH level (r=0.781, p<0.01) than serum FSH (r=-0.412, p<0.01). The cut-off value of serum AMH levels for poor response was 1.05 ng/mL (receiver operating characteristic [ROC] curves/area under the curve [AUC], ROCAUC=0.85, sensitivity 74%, specificity 87%). Hyper response cut-off value was 3.55 ng/mL (ROCAUC=0.91, sensitivity 94%, specificity 81%). When the study group was divided according to the serum AMH levels (low: <1.05 ng/mL, middle: 1.05 ng/mL - 3.55 ng/mL, high: >3.55 ng/mL), the groups showed no statistical differences in mature oocyte rates (71.6% vs. 76.5% vs. 74.8%) or fertilization rates (76.9% vs. 76.6% vs. 73.8%), but showed significant differences in clinical pregnancy rates (21.7% vs. 24.1% vs. 40.8%, p=0.017). Conclusion The serum AMH level can be used to predict the number of oocytes retrieved in patients, distinguishing poor and high responders. PMID:22384435

  5. Ovarian Cancer FAQ

    MedlinePlus

    ... Ovarian Cancer Patient Education FAQs Ovarian Cancer Patient Education Pamphlets - Spanish Ovarian Cancer FAQ096, April 2015 PDF Format Ovarian ... Your Practice Patient Safety & Quality Payment Reform (MACRA) Education & Events Annual ... Pamphlets Teen Health About ACOG About Us Leadership & ...

  6. 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.

  7. 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 ...

  8. An IL6-correlated signature in serous epithelial ovarian cancer associates with growth factor response

    PubMed Central

    2013-01-01

    Background Epithelial ovarian cancer (EOC) is one of the most lethal gynecological cancers; the majority of EOC is the serous histotype and diagnosed at advanced stage. IL6 is the cytokine that has been found most frequently associated with carcinogenesis and progression of serous EOCs. IL6 is a growth-promoting and anti-apoptotic factor, and high plasma levels of IL6 in advanced stage EOCs correlate with poor prognosis. The objective of the present study was to identify IL6 co-regulated genes and gene network/s in EOCs. Results We applied bioinformatics tools on 7 publicly available data sets containing the gene expression profiles of 1262 EOC samples. By Pearson's correlation analysis we identified, in EOCs, an IL6-correlated gene signature containing 40 genes mainly associated with proliferation. 33 of 40 genes were also significantly correlated in low malignant potential (LMP) EOCs, while 7 genes, named C5AR1, FPR1, G0S2, IL8, KLF2, MMP19, and THBD were IL6-correlated only in advanced stage EOCs. Among the 40-gene signature EGFR ligand HBEGF, genes of the EGR family members and genes encoding for negative feedback regulators of growth factor signaling were included. The results obtained by Gene Set Enrichment and Ingenuity Pathway Analyses enabled the identification, respectively, of gene sets associated with ‘early growth factor response’ for the 40-gene signature, and a biological network related to ‘thrombosis and cardiovascular disease’ for the 7-gene signature. In agreement with these results, selected genes from the identified signatures were validated in vitro by real time RT-PCR in serous EOC cell lines upon stimulation with EGF. Conclusions Serous EOCs, independently of their aggressiveness, co-regulate IL6 expression together with that of genes associated to growth factor signaling, arguing for the hypothesis that common mechanism/s driven by EGFR ligands characterize both advanced-stage and LMP EOCs. Only advanced-stage EOCs appeared to be

  9. Strategies for Controlled Ovarian Stimulation in the Setting of Ovarian Aging.

    PubMed

    Ata, Baris; Seli, Emre

    2015-11-01

    In the context of assisted reproduction, the term ovarian aging is often used to refer to declining potential of ovaries to produce oocytes in adequate number or quality in response to controlled ovarian stimulation (COS). Different aspects of COS have been modified with the intention to increase the number and quality of oocytes obtained for in vitro fertilization. In the setting of ovarian aging, suppression of the luteinizing hormone (LH) surge with gonadotropin-releasing hormone (GnRH) antagonist or short GnRH agonist protocol and stimulation with a daily gonadotropin dosage of ≤ 300 IU/day seem to be appropriate first choices, and there is a strong need for well-designed randomized controlled trials investigating effects of addition of LH activity, estradiol priming, transdermal testosterone administration, and growth hormone supplementation. Given the lack of high-quality evidence showing effectiveness of one approach over another, other factors such as duration of stimulation, total gonadotropin consumption and cost of medication, patient friendliness, and possible side effect profiles must be considered in tailoring the COS protocol according to each individual's needs and desires.

  10. 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

  11. [Anti-Müllerian hormone, an endocrine predictor of the response to ovarian stimulation in the bovine species].

    PubMed

    Monniaux, D; Rico, C; Larroque, H; Dalbiès-Tran, R; Médigue, C; Clément, F; Fabre, S

    2010-01-01

    The strong between-animal variability in the number of ovulations and embryos produced after ovarian stimulation by gonadotropins is a major limit to the development of embryo biotechnologies in cattle. In reproductive medicine, anti-mullerian hormone (AMH) is now widely used as an endocrine marker of the ovarian follicular reserve. In the cow, as in the woman, AMH is secreted by the granulosa cells of growing follicles. We have shown recently that in the cow, AMH is a very good endocrine marker of the population of small antral follicles that constitute the direct target of ovarian stimulatory treatments. AMH concentration measured in plasma before treatment varies between animals and is positively correlated to the number of ovulations and transferable embryos produced after an ovarian stimulatory treatment. Interestingly, AMH concentrations can remain stable over several months for each animal. Moreover, the number of embryos produced after ovarian stimulation is highly repeatable and has a relatively good heritability. From these observations, we propose the determination of AMH concentration in the plasma of a potential donor cow as a simple predictive method to evaluate both its level of ovarian activity and its capacity to produce high or low numbers of embryos. Optimal conditions for implementing this diagnostic test in cattle remain to be defined considering the age, the breed, the physiological status and the environmental factors related to breeding conditions for each animal. PMID:20580592

  12. Mifepristone and ovarian function.

    PubMed

    Curry, T E; Nothnick, W B

    1996-06-01

    In summary, RU 486 has been a powerful instrument in delineating progesterone action on the ovary. However, early experiments using RU 486 must be interpreted with the understanding that systemic administration of the antiprogestin may have had extraovarian sites of action, such as at the hypothalamic-pituitary axis or at the adrenal, that in turn led to indirect ovarian responses. Treatment with progesterone, agonist, or antagonist at periods during which the ovary lacks progesterone receptors would further suggest extraovarian sites of action or nongenomic mechanisms of action. Furthermore, the dose of ligand or antagonist administered and the hormonal milieu at the time of administration may dictate the ovarian response (Espey L, personal communication). For example, low doses of exogenous progesterone may elicit a biologic response, whereas high doses are without effect or may inhibit the biologic effect observed at lower doses. Although RU 486 is classically described as an antiprogestin, agonist actions have been observed in addition to its the well documented antiglucocorticoid effects. All of these variables may contribute to the confounding observations of progesterone and RU 486 action on the ovary. Regardless of these caveats, experimental paradigms have demonstrated that RU 486, either indirectly or directly, regulates ovarian folliculogenesis, stimulates and/or inhibits steroidogenesis depending on the species and time of RU 486 administration, inhibits ovulation, and modulates luteal function. These findings supports a progesterone-dependent mechanism in these varied aspects of ovarian function.

  13. Endocrine and ovarian responses associated with the first-wave dominant follicle in cattle.

    PubMed

    Badinga, L; Driancourt, M A; Savio, J D; Wolfenson, D; Drost, M; De La Sota, R L; Thatcher, W W

    1992-11-01

    To examine endocrine and biochemical differences between dominant and subordinate follicles and how the dominant follicle affects the hypothalamic-pituitary-ovarian axis in Holstein cows, the ovary bearing the dominant follicle was unilaterally removed on Day 5 (n = 8), 8 (n = 8), or 12 (n = 8) of synchronized estrous cycles. Follicular development was followed daily by ultrasonography from the day of detected estrus (Day 0) until 5 days after ovariectomy. Aromatase activity and steroid concentrations in first-wave dominant and subordinate follicles were measured. Intact dominant and subordinate follicles were cultured in 4 ml Minimum Essential Medium supplemented with 100 microCi 3H-leucine to evaluate de novo protein synthesis. Five days after unilateral ovariectomy, cows were resynchronized and the experiment was repeated. Follicular growth was characterized by the development of single large dominant follicles, which was associated with suppression of other follicles. Concentrations of estradiol-17 beta (E2) in follicular fluid and aromatase activity of follicular walls were higher in dominant follicles (438.9 +/- 45.5 ng/ml; 875.4 +/- 68.2 pg E2/follicle) compared to subordinate follicles (40.6 +/- 69.4 ng/ml; 99.4 +/- 104.2 pg E2/follicle). Aromatase activity in first-wave dominant follicles was higher at Days 5 (1147.1 +/- 118.1 pg E2/follicle) and 8 (1028.2 +/- 118.1 pg E2/follicle) compared to Day 12 (450.7 +/- 118.1 pg E2/follicle). Concentrations of E2 and androstenedione in first-wave dominant follicles were higher at Day 5 (983.2 +/- 78.2 and 89.5 +/- 15.7 ng/ml) compared to Days 8 (225.1 +/- 78.6 and 5.9 +/- 14.8 ng/ml) and 12 (108.5 +/- 78.6 and 13.0 +/- 14.8 ng/ml). Concentrations of progesterone in subordinate follicles increased linearly between Days 5 and 12 of the estrous cycle. Plasma concentrations of FSH increased from 17.9 +/- 1.4 to 32.5 +/- 1.4 ng/ml between 0 and 32 h following unilateral removal of the ovary with the first-wave dominant

  14. Contemporary phase III clinical trial endpoints in advanced ovarian cancer: assessing the pros and cons of objective response rate, progression-free survival, and overall survival.

    PubMed

    Tate Thigpen, J

    2015-01-01

    Among gynecologic cancers, ovarian cancer provides the greatest challenge because 75% to 80% of patients present with stage III/IV disease. Over the last 40 years, a series of large trials conducted by the Gynecologic Oncology Group and other cooperative groups has produced striking improvements in patient outcome; but the majority still dies of their disease. Further research in both the laboratory and the clinic is essential to continued improvement in patient management. Clinical trials, however, have become a major challenge because of issues with trial endpoints. Historically, overall survival (OS) has been regarded as the "gold standard" of endpoints. Lack of effective treatment for patients who progressed on or recurred after front-line therapy allowed trials to avoid obfuscation of OS by post-progression therapy. More recently, studies have identified over 20 agents active against ovarian cancer. Reasonable evidence shows that effective post-progression therapy with multiple lines of active agents can render the survival endpoint uninterpretable. Two other endpoints avoid this problem. The objective response rate, assessed by the Response Evaluation Criteria in Solid Tumors (RECIST), is an accepted endpoint for accelerated approval in ovarian cancer. More importantly, progression-free survival (PFS), measured from study entry to progression of disease, avoids post-progression therapy completely. Without effective post-progression therapy (prior to 1990), data show that PFS is a surrogate for OS. Recent experience with 4 large trials of bevacizumab shows that PFS can be accurately assessed if progression is clearly defined and if timing of assessments is consistent in all study arms. Acceptance of PFS as the optimal endpoint for ovarian cancer trials by investigators and regulatory agencies is crucial to further advances in management because effective post-progression therapy has rendered differences in OS virtually impossible to assess reliably.

  15. Abnormal luteinizing hormone response patterns to synthetic gonadotrophin releasing hormone in patients with polycystic ovarian syndrome.

    PubMed

    Katz, M; Carr, P J

    1976-08-01

    Basal gonadotrophin and sex steroid levels and responses to an intravenous injection of 100 mug gonadotrophin releasing hormone (Gn-RH) have been studied in 15 patients with polycystic ovaries. Mean basal LH concentration was raised and an excessive, exaggerated and prolonged response was observed after Gn-RH treatment, but patients could further be subdivided into two functional groups on the basis of their basal LH values and LH response patterns. Evidence was also produced which suggested a breakdown in the negative feedback mechanism in these patients.

  16. 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.

  17. 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.

  18. 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.

  19. Unique responses of midbrain CART neurons in macaques to ovarian steroids.

    PubMed

    Lima, F B; Henderson, J A; Reddy, A P; Tokuyama, Y; Hubert, G W; Kuhar, M J; Bethea, C L

    2008-08-28

    CART (cocaine and amphetamine regulated transcript) is a neuropeptide involved in the control of several physiological processes, such as response to psychostimulants, food intake, depressive diseases and neuroprotection. It is robustly expressed in the brain, mainly in regions that control emotional and stress responses and it is regulated by estrogen in the hypothalamus. There is a distinct population of CART neurons located in the vicinity of the Edinger-Westphal nucleus of the midbrain that also colocalize urocortin-1. The aims of this study were 1) to determine the distribution of CART immunoreactive neurons in the monkey midbrain, 2) to examine the effects of estrogen (E) and progesterone (P) on midbrain CART mRNA and peptide expression and 3) to determine whether midbrain CART neurons contain steroid receptors. Adult female rhesus monkeys (Macaca mulatta) were spayed and either treated with placebo (OVX), estrogen alone (E), progesterone alone (P) or E+P. Animals were prepared (a) for RNA extraction followed by microarray analysis and quantitative (q) RT-PCR (n=3/group); (b) for immunohistochemical analysis of CART and CART+tryptophan hydroxylase (TPH), CART+estrogen receptors (ER) or CART+progesterone receptors (n=5/group) and (c) for Western blots (n=3/group). Both E- and E+P-administration decreased CART gene expression on the microarray and with qRT-PCR. Stereological analysis of CART immunostaining at five levels of the Edinger-Westphal nucleus indicated little effect of E or E+P administration on the area of CART immunostaining. However, P administration increased CART-immunopositive area in comparison to the OVX control group with Student's t-test, but not with ANOVA. CART 55-102 detection on Western blot was unchanged by hormone administration. ERbeta and PR were detected in CART neurons and CART fibers appeared to innervate TPH-positive serotonin neurons in the dorsal raphe. In summary, E decreased CART mRNA, but this effect did not translate to the

  20. 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) ...

  1. 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).

  2. What Is Ovarian Cancer?

    MedlinePlus

    ... the key statistics about ovarian cancer? What is ovarian cancer? Cancer starts when cells in the body begin ... section . Other cancers that are similar to epithelial ovarian cancer Primary peritoneal carcinoma Primary peritoneal carcinoma (PPC) is ...

  3. 40 CFR 716.25 - Adequate file search.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Adequate file search. 716.25 Section... ACT HEALTH AND SAFETY DATA REPORTING General Provisions § 716.25 Adequate file search. The scope of a person's responsibility to search records is limited to records in the location(s) where the...

  4. 40 CFR 716.25 - Adequate file search.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Adequate file search. 716.25 Section... ACT HEALTH AND SAFETY DATA REPORTING General Provisions § 716.25 Adequate file search. The scope of a person's responsibility to search records is limited to records in the location(s) where the...

  5. 40 CFR 716.25 - Adequate file search.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Adequate file search. 716.25 Section... ACT HEALTH AND SAFETY DATA REPORTING General Provisions § 716.25 Adequate file search. The scope of a person's responsibility to search records is limited to records in the location(s) where the...

  6. 40 CFR 716.25 - Adequate file search.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Adequate file search. 716.25 Section... ACT HEALTH AND SAFETY DATA REPORTING General Provisions § 716.25 Adequate file search. The scope of a person's responsibility to search records is limited to records in the location(s) where the...

  7. 40 CFR 716.25 - Adequate file search.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Adequate file search. 716.25 Section... ACT HEALTH AND SAFETY DATA REPORTING General Provisions § 716.25 Adequate file search. The scope of a person's responsibility to search records is limited to records in the location(s) where the...

  8. "Something Adequate"? In Memoriam Seamus Heaney, Sister Quinlan, Nirbhaya

    ERIC Educational Resources Information Center

    Parker, Jan

    2014-01-01

    Seamus Heaney talked of poetry's responsibility to represent the "bloody miracle", the "terrible beauty" of atrocity; to create "something adequate". This article asks, what is adequate to the burning and eating of a nun and the murderous gang rape and evisceration of a medical student? It considers Njabulo…

  9. Basic mechanisms of ovarian endocrine function

    PubMed Central

    Schomberg, David W.

    1978-01-01

    This review outlines the current understanding of ovarian endocrine development and regulation with both physiological and biochemical background to provide a framework applicable to problems concerning environmental agents and ovarian endocrine function. Two approaches are used. First, the endocrine regulation of follicle development and corpus luteum function is considered in the classical sense, i.e., viewing these structures as gonadotropin-responsive units undergoing a programmed sequence of development and differentiation. Secondly, a relatively new area of ovarian physiology concerned with intra-ovarian regulation is explored, since this area holds potential for exploration of the direct effects of toxicological or environmental agents upon gonadal endocrine cells. PMID:17539154

  10. Cediranib combined with chemotherapy reduces tumor dissemination and prolongs the survival of mice bearing patient-derived ovarian cancer xenografts with different responsiveness to cisplatin.

    PubMed

    Decio, Alessandra; Cesca, Marta; Bizzaro, Francesca; Porcu, Luca; Bettolini, Rossana; Ubezio, Paolo; Taraboletti, Giulia; Belotti, Dorina; Giavazzi, Raffaella

    2015-10-01

    Cediranib is a pan-vascular endothelial growth factor receptor tyrosine kinase inhibitor that affects tumor angiogenesis and is under investigation in clinical studies on ovarian cancer. Using a panel of eleven patient-derived ovarian cancer xenografts (EOC-PDX) growing orthotopically in the peritoneal cavity of nude mice we investigated the effect of cediranib as monotherapy or in combination with chemotherapy on overall survival (primary endpoint, at euthanasia), and tumor dissemination and metastasis in the peritoneal cavity (secondary endpoint, interim analysis). The response of EOC-PDX to cediranib varied (increment of lifespan, ILS between 12 and 85 %) in the different EOC-PDX, independently from tumor responsiveness to cisplatin (DDP). Cediranib combined with DDP and in maintenance regimen prolonged the survival of mice bearing EOC-PDX with different responsiveness to DDP (ILS between 34 and 224 % with only DDP and between 135 and 337 % with DDP plus Cediranib); survival was extended with the addition of paclitaxel to chemotherapy (50-77 % complete remissions). Cediranib reduced ascites of advanced EOC-PDX, but had limited effect on tumor dissemination; only combined with chemotherapy, ascites and metastases were both reduced. The reduction of tumor dissemination was associated to the increase of overall survival. In conclusion, the response to cediranib differs in the various EOC-PDX, reproducing the heterogeneous response of cancer patients to angiogenesis inhibitors. Cediranib potentiated chemotherapy, significantly inhibiting tumor progression and dissemination to metastatic organs, even in tumors poorly responsive to DDP. EOC-PDX preclinical models with different responsiveness to Cediranib may help in identifying determinants of response to cediranib and mechanisms of adaptation to antiangiogenic treatments.

  11. 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.

  12. 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

  13. 34 CFR 85.900 - Adequate evidence.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Adequate evidence. 85.900 Section 85.900 Education Office of the Secretary, Department of Education GOVERNMENTWIDE DEBARMENT AND SUSPENSION (NONPROCUREMENT) Definitions § 85.900 Adequate evidence. Adequate evidence means information sufficient to support...

  14. 12 CFR 380.52 - Adequate protection.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 5 2012-01-01 2012-01-01 false Adequate protection. 380.52 Section 380.52... ORDERLY LIQUIDATION AUTHORITY Receivership Administrative Claims Process § 380.52 Adequate protection. (a... interest of a claimant, the receiver shall provide adequate protection by any of the following means:...

  15. 12 CFR 380.52 - Adequate protection.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 5 2013-01-01 2013-01-01 false Adequate protection. 380.52 Section 380.52... ORDERLY LIQUIDATION AUTHORITY Receivership Administrative Claims Process § 380.52 Adequate protection. (a... interest of a claimant, the receiver shall provide adequate protection by any of the following means:...

  16. 12 CFR 380.52 - Adequate protection.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 5 2014-01-01 2014-01-01 false Adequate protection. 380.52 Section 380.52... ORDERLY LIQUIDATION AUTHORITY Receivership Administrative Claims Process § 380.52 Adequate protection. (a... interest of a claimant, the receiver shall provide adequate protection by any of the following means:...

  17. 21 CFR 1404.900 - Adequate evidence.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Adequate evidence. 1404.900 Section 1404.900 Food and Drugs OFFICE OF NATIONAL DRUG CONTROL POLICY GOVERNMENTWIDE DEBARMENT AND SUSPENSION (NONPROCUREMENT) Definitions § 1404.900 Adequate evidence. Adequate evidence means information sufficient...

  18. 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. PMID:26667040

  19. The value of anti-Müllerian hormone measurement in the long GnRH agonist protocol: association with ovarian response and gonadotrophin-dose adjustments

    PubMed Central

    Anckaert, Ellen; Smitz, Johan; Schiettecatte, Johan; Klein, Bjarke M; Arce, Joan-Carles

    2012-01-01

    BACKGROUND This study evaluated the predictive value of serum and follicular fluid (FF) concentrations of anti-Müllerian hormone (AMH) with respect to treatment outcome variables in an IVF cycle. METHODS A retrospective analysis was performed with data from 731 normogonadotrophic women undergoing controlled ovarian stimulation after stimulation with highly purified menotrophin (HP-hMG) or rFSH following a long GnRH agonist protocol. RESULTS In both treatment groups, the serum AMH concentration at the start of the stimulation was significantly (P < 0.001) positively correlated with the serum levels of estradiol (HP-hMG: r = 0.45; rFSH: r = 0.55), androstenedione (HP-hMG: r = 0.50; rFSH: 0.49) and total testosterone (HP-hMG: r = 0.40; rFSH: r = 0.36) at the end of the stimulation as well as the number of oocytes retrieved (HP-hMG: r = 0.48; rFSH: r = 0.62), the AMH concentration in FF (HP-hMG: r = 0.55; rFSH: 0.61) and the serum progesterone concentration (HP-hMG: r = 0.39; rFSH: r = 0.50) at oocyte retrieval. For both treatments, serum AMH at the start of the stimulation was a good predictor of the need to increase or decrease the gonadotrophin dose on stimulation day 6 and of ovarian response below (<7 oocytes) or above (>15 oocytes) the target. No significant relationships were observed between serum AMH and embryo quality or ongoing pregnancy. CONCLUSION The serum AMH concentration at the start of the stimulation in IVF patients down-regulated with GnRH agonist in the long protocol revealed a positive relationship with ovarian response to gonadotrophins in terms of oocytes retrieved and accompanying endocrine response. AMH is a good predictor of the need for gonadotrophin-dose adjustment on stimulation day 6 for patients with a fixed starting dose, but a poor predictor of embryo quality and pregnancy chances in individual patients. PMID:22473395

  20. [Second surgery in the management of ovarian cancer].

    PubMed

    Scarabelli, C; Campagnutta, E; Zarrelli, A; De Piero, G; Sopracordevole, F; Visentin, M C; Giorda, G; Sasso, G M; Parin, A; Gallo, A

    1994-01-01

    The aim of this study was to evaluate the value of second surgery in the combined and multidisciplinary treatment of mullerian ovarian cancer. A retrospective study was carried out in 86 consecutive patients with advances stages of mullerian ovarian cancer (stage 3-4) referred to the Division of Gynecological Surgical Oncology of the Oncological Reference Centre at Aviano for continuation of treatment following initial surgery and chemotherapy performed in various peripheral institutions. Second surgery only revealed 11.6% of complete endocelomatic pathological responses (10 patients) to earlier treatments; among the 76 patients with persistent disease it was possible to achieve optimal redebulking in 50 (65.8%) (31 R0 and 19 R1 after second surgery), whereas it was not possible to perform adequate second surgery in 26 (34.2%). The impact of second surgery on the probability of survival (mean survival rate) was highly significant in the 50 patients in whom it was possible to perform adequate second surgery compared to the non-operated group (14.34 months versus 6.10, chi square = 12.671, p = 0.0004). The authors underline both the prognostic value of lymph node status with increased mortality among patients with positive retro-peritoneal lymph nodes (LN+), and the value of retroperitoneal re-evaluation in predicting endo-peritoneal recidivation in patients with free abdomen who subsequently relapsed.

  1. STAT3 polymorphisms may predict an unfavorable response to first-line platinum-based therapy for women with advanced serous epithelial ovarian cancer.

    PubMed

    Permuth-Wey, Jennifer; Fulp, William J; Reid, Brett M; Chen, Zhihua; Georgeades, Christina; Cheng, Jin Q; Magliocco, Anthony; Chen, Dung-Tsa; Lancaster, Johnathan M

    2016-02-01

    Cancer stem cells (CSC) contribute to epithelial ovarian cancer (EOC) progression and therapeutic response. We hypothesized that germline single nucleotide polymorphisms (SNPs) in CSC-related genes may predict an initial therapeutic response for women newly diagnosed with EOC. A nested case-control design was used to study 361 women with advanced-stage serous EOC treated with surgery followed by first-line platinum-based combination therapy at Moffitt Cancer Center or as part of The Cancer Genome Atlas Study. "Cases" included 102 incomplete responders (IRs) and "controls" included 259 complete clinical responders (CRs) to therapy. Using Illumina genotyping arrays and imputation, DNA samples were evaluated for 5,509 SNPs in 24 ovarian CSC-related genes. We also evaluated the overall significance of each CSC gene using the admixture maximum likelihood (AML) test, and correlated genotype with EOC tumor tissue expression. The strongest SNP-level associations with an IR to therapy were identified for correlated (r(2) > 0.80) SNPs within signal transducer and activator of transcription 3 (STAT3) [odds ratio (OR), 2.24; 95% confidence interval (CI), 1.32-3.78; p = 0.0027], after adjustment for age, population stratification, grade and residual disease. At the gene level, STAT3 was significantly associated with an IR to therapy (pAML = 0.006). rs1053004, a STAT3 SNP in a putative miRNA-binding site, was associated with STAT3 expression (p = 0.057). This is the first study to identify germline STAT3 variants as independent predictors of an unfavorable therapeutic response for EOC patients. Findings suggest that STAT3 genotype may identify high-risk women likely to respond more favorably to novel therapeutic combinations that include STAT3 inhibitors. PMID:26264211

  2. 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.

  3. Response of Penaeus indicus females at two different stages of ovarian development to a lethal infection with Vibrio penaeicida.

    PubMed

    Avarre, J-C; Saulnier, D; Labreuche, Y; Ansquer, D; Tietz, A; Lubzens, Esther

    2003-01-01

    An association between vitellogenesis and the immune system was suggested in crustaceans from studies on plasma lipoproteins. The present research studies the effect of an experimentally induced bacterial infection on vitellogenesis in females of the shrimp Penaeus indicus, as a model for penaeid species. Pre-vitellogenic and vitellogenic P. indicus females were experimentally infected with an extremely pathogenic bacterium, Vibrio penaeicida. The peak in mortality occurred earlier in pre-vitellogenic animals than in vitellogenic ones, although the final mortality level ( approximately 64-74%) 52h post-infection was nearly the same for the two groups. Twenty hours after infection, the total number of haemocytes was significantly reduced in vitellogenic females while there was no change in the pre-vitellogenic group. Protein synthesis in ovaries was not significantly affected by infection, at the two stages of ovarian development. No differences were found in mRNA levels of shrimp ovarian peritrophin protein (SOP), but preliminary results showed that mRNA expression of vitellin (VT) was reduced in a heavily infected vitellogenic female. The total amount of lipids in the haemolymph of vitellogenic females was almost twice higher than that of pre-vitellogenic ones. However, there was no change in the total content of lipids, lipid classes and fatty acid distribution in haemolymph or hepatopancreas following infection. Although vitellogenic and pre-vitellogenic females probably respond differently to a lethal bacterial infection, physiological differences may be concealed by the rapid onset of mortality.

  4. Molecular imaging in ovarian cancer.

    PubMed

    Reyners, A K L; Broekman, K E; Glaudemans, A W J M; Brouwers, A H; Arts, H J G; van der Zee, A G J; de Vries, E G E; Jalving, M

    2016-04-01

    Ovarian cancer has a high mortality and novel-targeted treatment strategies have not resulted in breakthroughs for this disease. Insight into the molecular characteristics of ovarian tumors may improve diagnosis and selection of patients for treatment with targeted therapies. A potential way to achieve this is by means of molecular imaging. Generic tumor processes, such as glucose metabolism ((18)F-fluorodeoxyglucose) and DNA synthesis ((18)F-fluorodeoxythymidine), can be visualized non-invasively. More specific targets, such as hormone receptors, growth factor receptors, growth factors and targets of immunotherapy, can also be visualized. Molecular imaging can capture data on intra-patient tumor heterogeneity and is of potential value for individualized, target-guided treatment selection. Early changes in molecular characteristics during therapy may serve as early predictors of response. In this review, we describe the current knowledge on molecular imaging in the diagnosis and as an upfront or early predictive biomarker in patients with ovarian cancer. PMID:27141066

  5. Ovarian cancer stem cells enrichment.

    PubMed

    Yang, Lijuan; Lai, Dongmei

    2013-01-01

    The concept of cancer stem cells (CSCs) provides a new paradigm for understanding cancer biology. Cancer stem cells are defined as a minority of cancer cells with stem cell properties responsible for maintenance and growth of tumors. The targeting of CSCs is a potential therapeutic strategy to combat ovarian cancer. Ovarian epithelial cancer cells cultured in serum-free medium can form sphere cells. These sphere cells may be enriched for cancer stem cells (CSCs). The isolation of sphere cells from solid tumors is an important technique in studying cancer cell biology. Here we describe the isolation of sphere cells from primary ovarian cancer tissue, ascites fluid, and the cancer cell line SKOV3 with stem cell selection medium. PMID:23913228

  6. 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. PMID:24880980

  7. Ovarian and hormonal responses to a progesterone-releasing controlled internal drug releasing treatment in dietary-restricted goats.

    PubMed

    Tanaka, Tomomi; Fujiwara, Ken-Ichiro; Kim, Seungjoon; Kamomae, Hideo; Kaneda, Yoshihiro

    2004-08-01

    An experiment was conducted to evaluate the effects of dietary restriction on ovarian, endocrine (ovarian steroids and luteinizing hormone (LH) pulse) and metabolic (glucose, insulin and non-esterified fatty acid (NEFA)) profiles in goats treated with a progesterone-releasing controlled internal drug releasing (CIDR-G) device. Cycling goats were offered either a maintenance or a restricted (30% of requirement; n =4 per treatment) level of feeding. The dietary restriction was started on the day following ovulation. At 30-32 days after the start of food restriction, the goats received a prostaglandin F(2alpha) (2mg of dinoprost) injection followed by 10 days of CIDR-G treatment. Ovarian ultrasonographic images were monitored daily throughout the experiment and blood samples were collected daily just before the morning feeding for analysis of endocrine and metabolic profiles. Frequent blood samples (1 ml) were also collected at 10 min intervals for 8 h from -8 h to CIDR-G removal, and from 32 to 40 h after CIDR-G removal for analysis of LH pulses. Body weight was significantly (P < 0.05) decreased in the food-restricted animals. Oestrous behaviour and ovulation followed by a rise of plasma progesterone concentration were observed after the CIDR-G removal in all control animals but not in any of the food-restricted animals within 12 days after CIDR-G removal. The LH pulse frequency from 32 to 40 h after the CIDR-G removal was significantly (P < 0.05) lower in the food-restricted animals than in control animals (1.5 +/- 0.6 versus 3.8 +/- 0.5 pulses for 8 h). There was no significant difference in the glucose concentration in weekly plasma samples between control and food-restricted animals. Insulin concentrations from 2 weeks after the start of feed restriction were significantly (P < 0.05) lower in restricted animals than in control animals. The NEFA concentration in restricted animals was significantly (P < 0.05) increased after the start of feed restriction, and

  8. NAC1 modulates sensitivity of ovarian cancer cells to cisplatin by altering the HMGB1-mediated autophagic response.

    PubMed

    Zhang, Y; Cheng, Y; Ren, X; Zhang, L; Yap, K L; Wu, H; Patel, R; Liu, D; Qin, Z-H; Shih, I-M; Yang, J-M

    2012-02-23

    Nucleus accumbens-1 (NAC1), a nuclear factor belonging to the BTB/POZ gene family, is known to have important roles in proliferation and growth of tumor cells and in chemotherapy resistance. Yet, the mechanisms underlying how NAC1 contributes to drug resistance remain largely unclear. We report here that autophagy was involved in NAC1-mediated resistance to cisplatin, a commonly used chemotherapeutic drug in the treatment of ovarian cancer. We found that treatment with cisplatin caused an activation of autophagy in ovarian cancer cell lines, A2780, OVCAR3 and SKOV3. We further demonstrated that knockdown of NAC1 by RNA interference or inactivation of NAC1 by inducing the expression of a NAC1 deletion mutant that contains only the BTB/POZ domain significantly inhibited the cisplatin-induced autophagy, resulting in increased cisplatin cytotoxicity. Moreover, inhibition of autophagy and sensitization to cisplatin by NAC1 knockdown or inactivation were accompanied by induction of apoptosis. To confirm that the sensitizing effect of NAC1 inhibition on the cytotoxicity of cisplatin was attributed to suppression of autophagy, we assessed the effects of the autophagy inhibitors 3-methyladenosine and chloroquine, and small interfering RNAs (siRNAs) targeting beclin 1 or Atg5 on the cytotoxicity of cisplatin. Treatment with 3-methyladenosine, chloroquine or beclin 1 and Atg5-targeted siRNA also enhanced the sensitivity of SKOV3, A2780 and OVCAR3 cells to cisplatin, indicating that suppression of autophagy indeed renders tumor cells more sensitive to cisplatin. Regulation of autophagy by NAC1 was mediated by the high-mobility group box 1 (HMGB1), as the functional status of NAC1 was associated with the expression, translocation and release of HMGB1. The results of our study not only revealed a new mechanism determining cisplatin sensitivity but also identified NAC1 as a novel regulator of autophagy. Thus, the NAC1-mediated autophagy may be exploited as a new target for

  9. 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

  10. 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 one or more of these signs ...

  11. Real-time monitoring of cAMP response element binding protein signaling in porcine granulosa cells modulated by ovarian factors.

    PubMed

    He, Pei Jian; Fujimoto, Yasunori; Yamauchi, Nobuhiko; Hattori, Masa-Aki

    2006-10-01

    The present study was performed to establish a real-time monitoring of the cAMP response element binding protein (CREB) signalling using granulosa cells, and to assess the modulation of CREB activity by potential ovarian autocrine/paracrine and oocyte-derived factors. Granulosa cells were isolated from porcine follicles and cultured for 2 days, and then transfected with CRE-containing pGL3. The cells were directly stimulated or cultured with FSH, LH, forskolin, or a permeable cAMP analog, and/or IGF-I, EGF, bFGF, TGF-beta2 or TNF-alpha, or cumulus-oocyte complex (COCs) for the real-time monitoring of CREB signaling. The activation pattern of CREB signaling consisted of three distinct phases, i.e., burst, attenuation and refractory. In contrast to FSH, LH, and forskolin, a cAMP analog induced the prolonged activation, although three distinct phases were observed at its high concentration. Of all the autocrine/paracrine factors, only IGF-I slightly induced CREB activity. On the other hand, TGF-beta2 and TNF-alpha significantly repressed FSH-stimulated transcriptional activation of CREB by 30% (P < 0.05) and 45% (P < 0.05), respectively. Additionally, coculture with COCs caused a significant suppression of transcriptional activation of CREB signaling stimulated by FSH. These results indicate that ovarian autocrine/paracrine factors such as IGF-I, TGF-beta2, TNF-alpha and oocyte-derived factors modulate the CREB signaling. The present study provides a new approach for direct signaling study on transcription factors under the influences of potential factors.

  12. 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.

  13. Factors related to inflammation of the ovarian epithelium and risk of ovarian cancer.

    PubMed

    Ness, R B; Grisso, J A; Cottreau, C; Klapper, J; Vergona, R; Wheeler, J E; Morgan, M; Schlesselman, J J

    2000-03-01

    Previous epidemiologic observations consistently suggest that suppression of ovulation, tubal ligation, and hysterectomy reduce the risk of ovarian cancer and that perineal talc use increases the risk. We examined these and other risk factors in the context of a new hypothesis: that inflammation may play a role in ovarian cancer risk. Ovulation entails ovarian epithelial inflammation; talc, endometriosis, cysts, and hyperthyroidism may be associated with inflammatory responses of the ovarian epithelium; gynecologic surgery may preclude irritants from reaching the ovaries via ascension from the lower genital tract. We evaluated these risk factors in a population-based case-control study. Cases 20-69 years of age with a recent diagnosis of epithelial ovarian cancer (767) were compared with community controls (1,367). We found that a number of reproductive and contraceptive factors that suppress ovulation, including gravidity, breast feeding, and oral contraception, reduced the risk of ovarian cancer. Environmental factors and medical conditions that increased risk included talc use, endometriosis, ovarian cysts, and hyperthyroidism. Gynecologic surgery including hysterectomy and tubal ligation were protective. Tubal ligation afforded a risk reduction even 20 or more years after the surgery. The spectrum of associations provides support for the hypothesis that inflammation may mediate ovarian cancer risk.

  14. 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.

  15. Bisphenol A and ovarian steroidogenesis.

    PubMed

    Bloom, Michael S; Mok-Lin, Evelyn; Fujimoto, Victor Y

    2016-09-15

    Bisphenol A is widely used as a component in polycarbonate plastics for food and beverage packaging, epoxy linings for canned foods, and dental sealants, among other applications. Experimental literature demonstrates BPA's affinity for estrogen receptors and downstream effects on estrogen-responsive genes. Additional data suggest that BPA reduces endogenous estrogen synthesis, likely by antagonizing ovarian enzyme activities involved in sex-steroid hormone synthesis. More specifically, evidence indicates BPA-mediated disruption of STAR, CYP450scc, and HSD-3β in theca cells and CYP450 aromatase activity in granulosa cells. Yet the results of the few human studies reported to date are equivocal. It also remains in question the extent to which BPA penetrates developing ovarian follicles. Uncertainty as to the relevance of experimental BPA doses and administration routes for common human exposure levels limits extrapolation of experimental results. To more definitively address the potential risk of BPA on human ovarian steroidogenesis, additional experimental studies using biologically active BPA doses likely to reflect those within the ovarian follicle will be necessary, as will additional prospective investigations in human populations with the use of standardized assay methodology. PMID:27543890

  16. Quality control in ovarian cancer surgery.

    PubMed

    Hacker, N F

    2011-12-01

    This study is a literature review of papers in the English language dealing with quality control for ovarian cancer surgery. Quality control in surgery has long been a neglected area of medicine. Initial attempts were limited to cardiac surgery, but only very recently has there been any attempt to look at quality control in ovarian cancer surgery. Investigators from Hesse, Germany were the first to document the surgical quality of patients with ovarian cancer. Subsequently, investigators in the United States and other European countries have demonstrated that patients treated by gynaecological oncologists in large-volume tertiary institutions had the best outcomes. The Gynaecological Cancer Group of the European Organisation for Research and Treatment of Cancer has developed a series of process quality indicators for ovarian cancer surgery that could be used by surgeons or units to audit and improve their practice. These and or other initiatives are important, because pressure is coming from consumers, government, health care insurers and medical risk insurers for surgeons and hospitals to provide transparent patient outcome data. If the profession does not institute adequate internal regulation of the quality of ovarian cancer surgery, regulation is likely to be imposed by government.

  17. 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

  18. Ovarian response to oestrous synchronization protocol based on use of reduced doses of cloprostenol in cyclic goats.

    PubMed

    Duque-Bonisoli, C; Salvador, A; Díaz, T; Contreras-Solis, I

    2012-12-01

    The objective of this study was to assess the efficacy of two reduced doses vs a high/luteolytic dose of cloprostenol on luteolytic activity and synchronization of oestrus in cyclic goats. Experiment 1, included 24 goats randomly allocated to three groups: control group (group H) received a single high dose of cloprostenol (87.5 μg; 1.0 ml; i.m.) and M and L groups, which received half (43.75 μg; 0.5 ml) and a third (26.25 μg; 0.3 ml) of the highest dose, respectively. Experiment 2, included 24 goats randomly assigned to the same experimental groups. Each group was treated using two injections of cloprostenol administered 10 days apart to synchronize oestrus. Transrectal ultrasonographic scanning (US) was performed to detect the presence, size and development of corpora lutea and ovarian follicles. Furthermore, detection of oestrus was performed every 12 h between 24 and 72 h after the second injection of cloprostenol, and the luteolytic effect was verified by US. In Experiment 1, all goats that had corpora lutea at timing of treatment regressed their corpora lutea. In Experiment 2, the occurrence of oestrus and the interval between treatment to onset of oestrus were: 100%, 49.5 ± 3.0 h; 100%, 51.0 ± 3.0 h; and 75%, 56.0 ± 3.5 h for H, M and L groups, respectively. The development of preovulatory follicles and occurrence of subsequent corpora lutea were similar among groups. In summary, the use of 26.25 μg of cloprostenol is effective for the synchronization of oestrus in cyclic goats.

  19. Ovarian stem cells: From basic to clinical applications.

    PubMed

    Ozakpinar, Ozlem Bingol; Maurer, Anne-Marie; Ozsavci, Derya

    2015-05-26

    The field of reproductive biology has undergone significant developments in the last decade. The notion that there is a fixed reserve pool of oocytes before birth was established by Zuckerman in 1951. However, in 2004, an article published in nature challenged this central dogma of mammalian reproductive biology. Tilly's group reported the existence of ovarian germline stem cells (GSCs) in postnatal ovaries of mice and suggested that the bone marrow could be an extragonadal source of ovarian GSCs. These findings were strongly criticized; however, several independent groups have since successfully isolated and characterized ovarian GSCs in postnatal mice. The ovarian GSCs are located in the ovarian surface epithelium and express markers of undifferentiated GSCs. When transplanted into mouse ovaries, mouse ovarian GSCs could differentiate and produce embryos and offspring. Similarly, in a recent study, ovarian GSCs were found to be present in the ovaries of women of reproductive age. Conversely, there is increasing evidence that stem cells responsible for maintaining a healthy state in normal tissue may be a source of some cancers, including ovarian cancer. Cancer stem cells (CSCs) have been found in many tissues, including ovaries. Some researchers have suggested that ovarian cancer may be a result of the transformation and dysfunction of ovarian GSCs with self-renewal properties. Drug resistant and metastasis-generating CSCs are responsible for many important problems affecting ovarian cancer patients. Therefore, the identification of CSCs will provide opportunities for the development of new therapeutic strategies for treatments for infertility and ovarian cancer. In this article, we summarize the current understanding of ovarian GSCs in adult mammals, and we also discuss whether there is a relationship between GSCs and CSCs.

  20. Asbestos/NESHAP adequately wet guidance

    SciTech Connect

    Shafer, R.; Throwe, S.; Salgado, O.; Garlow, C.; Hoerath, E.

    1990-12-01

    The Asbestos NESHAP requires facility owners and/or operators involved in demolition and renovation activities to control emissions of particulate asbestos to the outside air because no safe concentration of airborne asbestos has ever been established. The primary method used to control asbestos emissions is to adequately wet the Asbestos Containing Material (ACM) with a wetting agent prior to, during and after demolition/renovation activities. The purpose of the document is to provide guidance to asbestos inspectors and the regulated community on how to determine if friable ACM is adequately wet as required by the Asbestos NESHAP.

  1. 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.

  2. Sodium Arsenite ± Hyperthermia Sensitizes p53-Expressing Human Ovarian Cancer Cells to Cisplatin by Modulating Platinum-DNA Damage Responses

    PubMed Central

    Muenyi, Clarisse S.; Pinhas, Allan R.; Fan, Teresa W.; Brock, Guy N.; Helm, C. William; States, J. Christopher

    2012-01-01

    Epithelial ovarian cancer (EOC) is the leading cause of gynecological cancer death in the United States. Cisplatin is a DNA damaging agent initially effective against EOC but limited by resistance. P53 plays a critical role in cellular response to DNA damage and has been implicated in EOC response to platinum chemotherapy. In this study, we examined the role of p53 status in EOC response to a novel combination of cisplatin, sodium arsenite, and hyperthermia. Human EOC cells were treated with cisplatin ± 20μM sodium arsenite at 37°C or 39°C for 1 h. Sodium arsenite ± hyperthermia sensitized wild-type p53-expressing (A2780, A2780/CP70, OVCA 420, OVCA 429, and OVCA 433) EOC cells to cisplatin. Hyperthermia sensitized p53-null SKOV-3 and p53-mutant (OVCA 432 and OVCAR-3) cells to cisplatin. P53 small interfering RNA (siRNA) transfection abrogated sodium arsenite sensitization effect. XPC, a critical DNA damage recognition protein in global genome repair pathway, was induced by cisplatin only in wild-type p53-expressing cells. Cotreatment with sodium arsenite ± hyperthermia attenuated cisplatin-induced XPC in wild-type p53-expressing cells. XPC siRNA transfection sensitized wild-type p53-expressing cells to cisplatin, suggesting that sodium arsenite ± hyperthermia attenuation of XPC is a mechanism by which wild-type p53-expressing cells are sensitized to cisplatin. Hyperthermia ± sodium arsenite enhanced cellular and DNA accumulation of platinum in wild-type p53-expressing cells. Only hyperthermia enhanced platinum accumulation in p53-null cells. In conclusion, sodium arsenite ± hyperthermia sensitizes wild-type p53-expressing EOC cells to cisplatin by suppressing DNA repair protein XPC and increasing cellular and DNA platinum accumulation. PMID:22331493

  3. Monitor Therapeutic Response of Human Ovarian Cancer to 17-DMAG by Non-invasive PET imaging with 64Cu-DOTA-Trastuzumab

    PubMed Central

    Niu, Gang; Li, Zibo; Cao, Qizhen; Chen, Xiaoyuan

    2012-01-01

    Purposes 17-DMAG, a heat shock protein 90 (Hsp90) inhibitor, has been intensively investigated for cancer therapy and is undergoing clinical trials. Human epidermal growth factor receptor 2 (HER-2) is one of the client proteins of Hsp90 and its expression is decreased upon 17-DMAG treatment. In this study, we aimed to non-invasively monitor the HER-2 response to 17-DMAG treatment in xenografted mice. Methods The sensitivity of human ovarian cancer SKOV-3 cells to 17-DMAG in vitro was measured by MTT assay. HER-2 expression of SKOV-3 cells was determined by flow cytometry. Nude mice bearing SKOV-3 tumors were treated with 17-DMAG and the therapeutic efficacy was evaluated by tumor size measurement. Both treated and control mice were imaged with microPET using 64Cu-DOTA-trastuzumab and 18F-FDG. Biodistribution studies, immunofluorescence staining were performed to validate the microPET results. Results SKOV-3 cells are sensitive to 17-DMAG treatment, in a dose dependent manner, with an IC50 value of 68.7 nM after 72 h incubation. The tumor growth curve supported the inhibition effect of 17-DMAG on SKOV-3 tumors. Quantitative microPET imaging showed that 64Cu-DOTA-trastuzumab had prominent tumor activity accumulation in untreated SKOV-3 tumors, which was significantly reduced in 17-DMAG treated tumors. There was no uptake difference detected by FDG PET. Immunofluorescence staining confirmed the significant reduction in tumor HER-2 level upon 17-DMAG treatment. Conclusion The early response to anti-Hsp90 therapy was successfully monitored by quantitative PET using 64Cu-DOTA-trastuzumab. This approach may be valuable in monitoring the therapeutic response in HER-2-positive cancer patients under 17-DMAG treatment. PMID:19440708

  4. Supervision of Student Teachers: How Adequate?

    ERIC Educational Resources Information Center

    Dean, Ken

    This study attempted to ascertain how adequately student teachers are supervised by college supervisors and supervising teachers. Questions to be answered were as follows: a) How do student teachers rate the adequacy of supervision given them by college supervisors and supervising teachers? and b) Are there significant differences between ratings…

  5. Small Rural Schools CAN Have Adequate Curriculums.

    ERIC Educational Resources Information Center

    Loustaunau, Martha

    The small rural school's foremost and largest problem is providing an adequate curriculum for students in a changing world. Often the small district cannot or is not willing to pay the per-pupil cost of curriculum specialists, specialized courses using expensive equipment no more than one period a day, and remodeled rooms to accommodate new…

  6. Toward More Adequate Quantitative Instructional Research.

    ERIC Educational Resources Information Center

    VanSickle, Ronald L.

    1986-01-01

    Sets an agenda for improving instructional research conducted with classical quantitative experimental or quasi-experimental methodology. Includes guidelines regarding the role of a social perspective, adequate conceptual and operational definition, quality instrumentation, control of threats to internal and external validity, and the use of…

  7. An Adequate Education Defined. Fastback 476.

    ERIC Educational Resources Information Center

    Thomas, M. Donald; Davis, E. E. (Gene)

    Court decisions historically have dealt with educational equity; now they are helping to establish "adequacy" as a standard in education. Legislatures, however, have been slow to enact remedies. One debate over education adequacy, though, is settled: Schools are not financed at an adequate level. This fastback is divided into three sections.…

  8. Funding the Formula Adequately in Oklahoma

    ERIC Educational Resources Information Center

    Hancock, Kenneth

    2015-01-01

    This report is a longevity, simulational study that looks at how the ratio of state support to local support effects the number of school districts that breaks the common school's funding formula which in turns effects the equity of distribution to the common schools. After nearly two decades of adequately supporting the funding formula, Oklahoma…

  9. 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

  10. 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.

  11. The use of ovarian reserve markers in IVF clinical practice: a national consensus.

    PubMed

    La Marca, Antonio; Ferraretti, Anna Pia; Palermo, Roberto; Ubaldi, Filippo M

    2016-01-01

    Ovarian reserve markers have been documented to perform very well in the clinical practice. While this is widely recognized, still now there is no consensus on how to use new biomarkers in the clinical practice. This study was conducted among Italian IVF centres using the Delphi technique, a validated consensus-building process. Briefly three consecutive questionnaires were developed for clinicians in charge of IVF centres. In the first rounds, participants were asked to rate the importance of a list of statements regarding the categorization of ovarian response and the diagnostic role of biomarkers. In round 3, participants were asked to rate their agreement and consensus on the list of statements derived from the first two rounds. There were 120 respondents. Consensus was achieved for many points: (a) poor ovarian response is predicted on the basis of the following: AMH < 1 ng/ml or AFC < 7, FSH ≥ 10 IU/l, age ≥ 40 yrs; (b) hyper-response is predicted on the basis of the following: AMH > 3 ng/ml or AFC > 14; (c) day 3 FSH measurement should always be associated to estradiol; (d) AMH can be measured on a random basis; (e) the measurement of the AFC with the 2D technology may be considered adequate and (f) the AFC should be measured in the early follicular phase and consists in the total number of 2-9 mm follicles in both the ovaries. The present study suggests that extensive consensus on the importance and use of new ovarian reserve markers to improve IVF safety and performance is already present among clinicians.

  12. Vanishing ovarian mass: Sarcoidosis.

    PubMed

    Turkay, Rustu; Bakir, Baris; Golabi, Uygar Cenik; Topuz, Samet; Ilhan, Huseyin Ridvan

    2012-01-01

    A woman was referred to our hospital with the working diagnosis of ovarian malignancy. While she was undergoing both clinical and radiological evaluation and monitoring, a decrease in the size of the ovarian mass was noted. After further evaluation via laboratory findings and tissue biopsy, we arrived at a final diagnosis of sarcoidosis, which is very unusual in the ovaries. Our case places emphasis on the importance of considering rare entities, such as ovarian sarcoidosis, and the importance of radiologic changes in solid ovarian mass dimensions over time.

  13. 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

  14. 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

  15. Ovarian Cancer Fact Sheet

    MedlinePlus

    ... States, ovarian cancer is the eighth most common cancer and the fifth leading cause of cancer death. Around one in every 60 ... States, ovarian cancer is the eighth most common cancer and the fifth leading cause of cancer death. Are some women more at ...

  16. 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 ...

  17. 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 ...

  18. Ovarian Cancer Stage II

    MedlinePlus

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

  19. Ovarian Cancer Stage I

    MedlinePlus

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

  20. 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

  1. Understanding emotional responses to breast/ovarian cancer genetic risk assessment: an applied test of a cognitive theory of emotion.

    PubMed

    Phelps, Ceri; Bennett, Paul; Brain, Kate

    2008-10-01

    This study explored whether Smith and Lazarus' (1990, 1993) cognitive theory of emotion could predict emotional responses to an emotionally ambiguous real-life situation. Questionnaire data were collected from 145 women upon referral for cancer genetic risk assessment. These indicated a mixed emotional reaction of both positive and negative emotions to the assessment. Hierarchical regression analyses revealed that the hypothesised models explained between 20% and 33% of the variance of anxiety, hope and gratitude scores, but only 10% of the variance for challenge scores. For the previously unmodelled emotion of relief, 31% of the variance was explained by appraisals and core relational themes. The findings help explain why emotional responses to cancer genetic risk assessment vary and suggest that improving the accuracy of individuals' beliefs and expectations about the assessment process may help subsequent adaptation to risk information.

  2. 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

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

    ClinicalTrials.gov

    2016-07-08

    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

  4. 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

  5. Uterine, ovarian, and production responses of lactating dairy cows to increasing dietary concentrations of menhaden fish meal.

    PubMed

    Mattos, R; Staples, C R; Williams, J; Amorocho, A; McGuire, M A; Thatcher, W W

    2002-04-01

    The primary objective was to determine whether the dietary polyunsaturated fatty acids, eicosapentaenoic (EPA, C20:5, n-3) and docosahexaenoic (DHA, C22:6, n-3), present in fish meal (FM) can attenuate uterine secretion of PGF2alpha in response to a challenge with estradiol and oxytocin in lactating dairy cows. Cycling multiparous cows (n = 32) were fed diets containing 0 (OFM), 2.6 (2.6FM), 5.2 (5.2FM), or 7.8% menhaden FM (7.8FM). The diet consisting of 7.8FM also contained fish oil (0.28% of dietary dry matter) to increase intake of EPA and DHA. Average dry matter intake was 24.9 kg/d and unaffected by diet. Combined intakes of EPA and DHA averaged 0, 12.8, 24.1, and 54.0 g/d from the OFM, 2.6FM, 5.2FM, and 7.8FM diets, respectively. At 30 to 34 d after initiation of dietary treatments, cows received an i.m. injection of 100 microg of GnRH followed by i.m. administration of 25 and 15 mg of PGF2alpha after 7 and 8 d, respectively. Synchronous ovulation was induced by an injection of 3000 IU of human chorionic gonadotropin (hCG) given 24 h later on d 9. Subsequent luteal phase increases in plasma progesterone concentrations did not differ (0.88 ng/ml per day). At 15 d after hCG injection, cows were injected with estradiol-17beta (3 mg, i.v.) at 0900 h and oxytocin (100 IU, i.v.) at 1300 h. Plasma PGF2alpha metabolite concentrations after oxytocin injection were reduced in cows fed diets containing FM compared with those fed OFM. Milk production (39.1 kg/d) and concentrations of fat, protein, or urea nitrogen in milk were not affected by diet. Feeding fish meal and fish oil containing eicosapentaenoic acid and docosahexaenoic acid reduced the proportion of n-6 fatty acids and increased that of n-3 fatty acids in milk in a dose-responsive manner. PMID:12018420

  6. 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.

  7. Can Ovarian Cancer Be Found Early?

    MedlinePlus

    ... Topic Signs and symptoms of ovarian cancer 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. Validation of the controlled ovarian stimulation impact measure (COSI): assessing the patient perspective

    PubMed Central

    2013-01-01

    Background Controlled Ovarian Stimulation (COS) is the first step for in vitro fertilization (IVF) treatment, a treatment often described and experienced as stressful to patients and their partners. COS also requires concerted efforts by the patients in administering medication and general compliance to treatment protocols. Little is known about the impacts on patients that may be specific to this important first step in treatment. The absence of a conceptually sound and well-validated measure assessing patient experience and functioning during ovarian stimulation has been an obstacle to understanding the impacts of ovarian stimulation on women pursuing IVF. To address this gap, the Controlled Ovarian Stimulation Impact Measure (COSI) was developed based upon accepted methods for designing patient reported outcome (PRO) measures. The purpose of this study was to psychometrically validate the COSI. Methods 267 patients from three countries (Ireland, United Kingdom, United States) were administered the COSI. Psychometric validation was conducted according to an a priori statistical analysis plan. Results The final 28-item COSI was found to have robust scale structure with four domains: Interference in Daily Life (Work and Home), Injection Burden, Psychological Health and Compliance Worry. Internal consistency of all domains was adequate (between 0.80 to 0.87) as was test-retest reliability (between 0.72-0.87). All a-priori hypotheses for convergent and known-groups validity tests were met. Conclusions There is a measurable impact of COS on patient functioning and well-being. The COSI is a well-developed and validated PRO measure of this impact. Future work should include examination of responsiveness and confirmation of concepts in non-western countries. PMID:23902854

  9. 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

  10. 4 CFR 200.14 - Responsibility for maintaining adequate safeguards.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... access. Proper control of personal data in any form associated with automated data systems shall be... persons within or outside the Board. (2) Access to and use of a system of records shall be permitted only..., access to records within a system of records shall be permitted only to the individual to whom the...

  11. 4 CFR 200.14 - Responsibility for maintaining adequate safeguards.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... access. Proper control of personal data in any form associated with automated data systems shall be... persons within or outside the Board. (2) Access to and use of a system of records shall be permitted only..., access to records within a system of records shall be permitted only to the individual to whom the...

  12. Anosmia and hypogonadism with ovarian mosaicism.

    PubMed

    Jones, J R; Kemmann, E; Cresci, J; Solish, G I

    1975-04-01

    An 18-year-old woman with anosmia and hypogonadotropic hypogonadism is presented. In addition endocrinologic evaluation revealed an apparent deficiency in pituitary growth hormone secretion in response to hypoglycemia and an ovarian insensitivity to exogenous gonadotropins. The ovaries, which on histologic examination appeared to be normal, upon karyotyping showed a chromosomal mosaicism, probably 46, XX/47, XXF+.

  13. Is a vegetarian diet adequate for children.

    PubMed

    Hackett, A; Nathan, I; Burgess, L

    1998-01-01

    The number of people who avoid eating meat is growing, especially among young people. Benefits to health from a vegetarian diet have been reported in adults but it is not clear to what extent these benefits are due to diet or to other aspects of lifestyles. In children concern has been expressed concerning the adequacy of vegetarian diets especially with regard to growth. The risks/benefits seem to be related to the degree of restriction of he diet; anaemia is probably both the main and the most serious risk but this also applies to omnivores. Vegan diets are more likely to be associated with malnutrition, especially if the diets are the result of authoritarian dogma. Overall, lacto-ovo-vegetarian children consume diets closer to recommendations than omnivores and their pre-pubertal growth is at least as good. The simplest strategy when becoming vegetarian may involve reliance on vegetarian convenience foods which are not necessarily superior in nutritional composition. The vegetarian sector of the food industry could do more to produce foods closer to recommendations. Vegetarian diets can be, but are not necessarily, adequate for children, providing vigilance is maintained, particularly to ensure variety. Identical comments apply to omnivorous diets. Three threats to the diet of children are too much reliance on convenience foods, lack of variety and lack of exercise.

  14. Critical appraisal of bevacizumab in the treatment of ovarian cancer.

    PubMed

    Yoshida, Hiroyuki; Yabuno, Akira; Fujiwara, Keiichi

    2015-01-01

    Bevacizumab is the first molecular-targeted agent to be used for the treatment of ovarian cancer. Bevacizumab is a humanized monoclonal antibody targeting vascular endothelial growth factor. Two randomized Phase III trials evaluated the combination of bevacizumab plus standard cytotoxic chemotherapy for first-line treatment of advanced ovarian cancer. Additional Phase III trials evaluated bevacizumab combined with cytotoxic chemotherapy in platinum-sensitive and platinum-resistant recurrent ovarian cancer. All these trials reported a statistically significant improvement in progression-free survival but not in overall survival. Furthermore, bevacizumab effectively improved the quality of life with regard to abdominal symptoms in recurrent ovarian cancer patients. Bevacizumab is associated with adverse events not commonly observed with cytotoxic agents used to treat gynecological cancers, such as hypertension, bleeding, thromboembolism, proteinuria, delayed wound healing, and gastrointestinal events. However, most of these events can be adequately managed by gynecologists. The clinical trial results with bevacizumab have supported its recent approval in Europe and the United States as a treatment for ovarian cancer. This review presents the latest evidence for bevacizumab therapy of ovarian cancer and describes selection of patients for personalized treatment. PMID:25960638

  15. Disulfiram/copper causes redox-related proteotoxicity and concomitant heat shock response in ovarian cancer cells that is augmented by auranofin-mediated thioredoxin inhibition

    PubMed Central

    Papaioannou, Margarita; Mylonas, Ioannis; Kast, Richard E.; Brüning, Ansgar

    2014-01-01

    A valuable strategy to develop new therapeutic options for a variety of diseases has been the identification of new targets and applications for already approved drugs, the so-called drug repositioning. Recurrent ovarian cancer is a nearly incurable malignancy for which new and effective treatments are urgently needed. The alcohol-deterring drug disulfiram has been shown to cause preferential cell death in a variety of cancer cells. In this study, it is shown that disulfiram mediates effective cell death in ovarian cancer cells by promoting a pro-oxidative intracellular environment in a copper-dependent mechanism. Within few hours of application, disulfiram caused irreversible cell damage associated with pronounced induction of the inducible heat shock proteins HSP70, HSP40, and HSP32. The small heat shock protein HSP27 was found to be covalently dimerized via oxidized disulfide bonds and precipitated in para-nuclear protein aggregates. Simultaneous inhibition of the cellular thioredoxin system by auranofin further enhanced the cytotoxic effect of disulfiram. These data indeed indicate that the combination of two approved drugs, the anti-alcoholic disulfiram and the anti-rheumatic auranofin, may be of interest for the treatment of recurrent and genotoxic drug-resistant ovarian cancer by inducing a proteotoxic cell death mechanism. PMID:25593981

  16. Adequate mathematical modelling of environmental processes

    NASA Astrophysics Data System (ADS)

    Chashechkin, Yu. D.

    2012-04-01

    In environmental observations and laboratory visualization both large scale flow components like currents, jets, vortices, waves and a fine structure are registered (different examples are given). The conventional mathematical modeling both analytical and numerical is directed mostly on description of energetically important flow components. The role of a fine structures is still remains obscured. A variety of existing models makes it difficult to choose the most adequate and to estimate mutual assessment of their degree of correspondence. The goal of the talk is to give scrutiny analysis of kinematics and dynamics of flows. A difference between the concept of "motion" as transformation of vector space into itself with a distance conservation and the concept of "flow" as displacement and rotation of deformable "fluid particles" is underlined. Basic physical quantities of the flow that are density, momentum, energy (entropy) and admixture concentration are selected as physical parameters defined by the fundamental set which includes differential D'Alembert, Navier-Stokes, Fourier's and/or Fick's equations and closing equation of state. All of them are observable and independent. Calculations of continuous Lie groups shown that only the fundamental set is characterized by the ten-parametric Galilelian groups reflecting based principles of mechanics. Presented analysis demonstrates that conventionally used approximations dramatically change the symmetries of the governing equations sets which leads to their incompatibility or even degeneration. The fundamental set is analyzed taking into account condition of compatibility. A high order of the set indicated on complex structure of complete solutions corresponding to physical structure of real flows. Analytical solutions of a number problems including flows induced by diffusion on topography, generation of the periodic internal waves a compact sources in week-dissipative media as well as numerical solutions of the same

  17. 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.

  18. Ovarian reserve markers in unexplained infertility patients treated with clomiphene citrate during intrauterine insemination

    PubMed Central

    Ulug, Pasa; Elmali, Ferhan

    2015-01-01

    Introduction The aim of this retrospective case control study was to identify predictors of ovarian response and pregnancy outcomes in intrauterine insemination (IUI). Material and methods One hundred women undergoing IUI cycles with clomiphene citrate were enrolled. The number of antral follicles and the total ovarian volume by ultrasound, and the basal levels of follicle-stimulating hormone (FSH), estradiol, and inhibin B on cycle day 3 were measured in groups that were divided according to ovarian response. The tests were also evaluated according to ovarian response and pregnancy outcomes. All analyses were performed using the Statistical Package for the Social Sciences, version 15.0 (SPSS, Chicago, IL, USA). Results The antral follicle count (AFC) was the best single predictor for ovarian response and pregnancy outcomes. The sensitivity and specificity for prediction of ovarian response were 81% and 78% for AFC at an optimum cutoff value of ≤ 13.1. Age was negatively correlated with ovarian volume (r = –0.280, p = 0.021) and AFC (r = –0.358, p = 0.003). Increasing FSH was associated with a reduction in AFC (r = –0.273, p = 0.025). The AFC was significantly correlated with ovarian volume (r = 0.660, p < 0.0001) and FSH (r = –0.273, p = 0.03). Conclusions Our data demonstrate that the AFC provides better prognostic information on the occurrence of ovarian response during clomiphene citrate stimulation for IUI. PMID:26788087

  19. Ovarian stimulation in patients with breast cancer.

    PubMed

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

    2015-01-01

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

  20. [Ovarian surface epithelium and its histogenic relation to ovarian cancer].

    PubMed

    Dietl, J; Buchholz, F; Stoll, P

    1986-09-01

    Approximately 80 to 90 per cent of adult ovarian cancers are assumed to originate from ovarian surface cells. A series of morphological and biochemical studies has been recently conducted to test this. The ovarian surface epithelium shows permanent morphological changes such as crypts, inclusion cysts, villous processes and different forms of müllerian epithelium. The unique nature of ovarian surface changes and their abrupt disappearance in immediately adjacent mesothelia suggest that local factors may play an important part in modifying the growth and morphogenesis of the epithelium of the ovarian surface. Whether these endogenous and/or exogenous factors may also induce surface neoplasia is a moot point.

  1. Talc and ovarian cancer

    SciTech Connect

    Hartge, P.; Hoover, R.; Lesher, L.P.; McGowan, L.

    1983-01-01

    The potential link between epithelial talc use and ovarian cancer was examined in records of women treated for pathologically confirmed epitherial ovarian cancer. We estimated the relative risk to talc users as 0.7 (95% confidence interval (CI) = 0.4 to 1.1). The estimate was unaffected by adjustment for race, age, and gravidity. Neither women who used talc on their diaphragms nor those who used it as body powder seemed to be at excess risk. Our data thus indicate no overall association between talc use and risk of ovarian cancer. Although a small group of women who specifically reported genital use of body talcum powders showed an excess relative risk, use of talc on a diaphragm, which would be the closest exposure to the ovaries, did not seem to elevate risk.

  2. Ovarian Lymphoma and Hydronephrosis

    PubMed Central

    Bernardini, Luca; Angeloni, Moira; Gogna, Paolo; Intersimone, Donatella; Fedeli, Franco

    2013-01-01

    Introduction: Ovarian lymphoma is a rare entity, and hydronephrosis from lymphoma is even rarer. Most reports describe a laparoscopic approach to the disease, but we report a case of hydroureteronephrosis associated with ovarian lymphoma managed completely by mini-invasive techniques. Case Report: A 51-year-old woman was referred to us for back pain and renal colic and computed tomography scan findings of right hydroureteronephrosis and a mass in the right mesorectum and uterosacral ligament. After magnetic resonance imaging was performed, the patient underwent laparoscopic adnexectomy and ureterolysis after ureteroscopy and stenting. Histology results showed diffuse B-cell lymphoma of the ovary occluding the ureter without infiltration. The patient has undergone 6 cycles of chemotherapy. Discussion: This is the first report to describe ovarian lymphoma and hydroureteronephrosis managed completely by laparoscopic surgery and endoscopy. Frequency in clinical practice, differential diagnosis, and endoscopic approach are discussed. The advantages of a multidisciplinary endoscopic team are underlined. PMID:24398216

  3. Ovarian cancer, Part II: Treatment.

    PubMed

    Ozols, R F

    1992-01-01

    The death rate from epithelial ovarian cancer has only slightly decreased in the past decade. In contrast, there have been dramatic improvements in the treatment of germ cell tumors of the ovary and the majority of patients even with advanced disease is now cured because of the development of effective platinum-based combination chemotherapy. Unfortunately, most patients with ovarian cancer have the epithelial histologic type, and only one third of these patients can be cured with standard approaches. It has recently been shown that a subset of patients with early stage ovarian cancer has a greater than 90% cure rate without chemotherapy. Consequently, a major focus of current research is to develop effective screening modalities in order to diagnose epithelial tumors when they are still confined to the ovaries and pelvis. Currently, three fourths of patients are diagnosed at the time the disease has spread throughout the peritoneal cavity, and the standard approach has been cytoreductive surgery followed by combination chemotherapy. The two-drug combination of carboplatin plus cyclophosphamide has now become the treatment of choice, although it is equally effective as and less toxic than a regimen of cisplatin plus cyclophosphamide. In addition, Taxol has been identified as an extremely active agent against this disease, and new Taxol-containing combinations are under clinical investigation. Clinical trials are also in progress with hexamethylmelamine and ifosfamide combinations as well as with more dose-intense regimens based on considerable retrospective evidence that survival is correlated with the dose intensity of platinum compounds. New agents such as WR2721, IL-3, and IL-1 alpha are undergoing clinical evaluation to determine whether the toxicities of platinum compounds can be decreased and lead to further exploitation of the dose response relationship. After induction chemotherapy, approximately 50% of patients will be in a clinical complete remission

  4. Polycystic ovarian disease: animal models.

    PubMed

    Mahajan, D K

    1988-12-01

    histologically, although some of the stromal cells appear hypertrophic. The anatomic features consequent to polycystic ovaries resulting from LL are similar to those in human PCOD, and both rat and human PCOD ovarian cells still retain the ability to respond to FSH/LH, LHRH, and unilateral ovariectomy. In the estradiol valerate rat model, although the anatomy and physiology of the ovary resemble those of PCOD patients, the progressive degeneration of the hypothalamus and the altered response of the pituitary to LHRH make this model inappropriate for studying the hypothalamic-pituitary-ovarian axis in the polycystic ovary condition.(ABSTRACT TRUNCATED AT 400 WORDS)

  5. Hypothalamic-pituitary-ovarian axis in uremic women.

    PubMed

    Swamy, A P; Woolf, P D; Cestero, R V

    1979-06-01

    Menstrual abnormalities are common with decreasing renal function and uremia. Maintenance hemodialysis therapy partially corrects some of the abnormalities. Since the pathophysiology of the menstural irregularities is unknown, the secretion of LH, FSH, estrogen, and PRL was studied under basal conditions and after provocative testing in 13 women undergoing chronic maintenance hemodialysis. Elevated LH concentrations were found in all six premenopausal (44.1 +/- 26.4 mlU/ml, normal follicular phase 4 to 30) and seven postmenopausal (246.1 +/- 171.4 mlU/ml, normal 35 to 200) women studied. FSH values were normal both in the premenopausal women (7.9 +/- 4.1 mlU/ml, normal 2 to 20) and in postmenopausal women (88.0 +/- 69.0 mlU/ml, normal 40 to 200). FSH and LH levels did not show typical ovulatory spikes in three of four women studied. Pulsatile hormonal release was absent. The pituitary response to LH-RH was adequate and prolonged, but the response to clomiphene citrate was variable. The study documents the existence of abnormalities at various levels of the hypothalamic-putuitary-ovarian axis.

  6. Retropancreatic Ovarian Tumor.

    PubMed

    Acharya, Soumyo Ranjan; Dasgupta, Prosenjit; Das, Subhobroto; Halder, Sandip; Panda, Nilanjan

    2016-06-01

    Retroperitoneal mucinous cystadenomas are rare lesions (less than 50 reported) characterized by presence of ovary like stroma of unknown origin. However, germinal component of ovary has never been found in them. The pancreas occasionally gives rise to mucinous cystadenomas, but they are always intrapancreatic. We report a unique case of a rare retroperitoneal mucinous cystadenomas with presence of ovarian follicles in a 45-year-old lady who presented with an abdominal mass. This was successfully excised. Though retroperitoneal mucinous cystadenomas are rare, presence of ovarian follicle (germ cell) in them has never been reported before. PMID:27358520

  7. 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.

  8. Prognostic factors in ovarian cancer.

    PubMed

    Friedlander, M L

    1998-06-01

    There is obvious merit in being able to accurately predict outcome and tailor treatment according to individual risk and potential for benefit. Epithelial ovarian cancers are characterized by a broad spectrum of biological behavior ranging from tumors that have an excellent prognosis and high likelihood of cure to those that progress rapidly and have a very poor prognosis. This wide clinical spectrum is partly reflected by a number of clinicopathological prognostic variables which include International Federation of Gynecology and Obstetrics stage, histologic subtype and grade, volume of residual tumor remaining after surgical resection, performance status, and age. There has been increasing interest by many groups to incorporate the independent prognostic variables into multivariate models that could better predict outcome. This approach does appear to allow the identification of different prognostic subsets and requires confirmation in prospective studies. There has been, and there continues to be a lot of effort in identifying new prognostic factors that have a biologic rationale and these will be discussed. Most of these new prognostic factors have not been subjected to rigorous testing and this will be clearly necessary before they find clinical application. This is an area that is rapidly evolving with the increased understanding of the molecular basis for ovarian carcinogenesis and progression coupled with technological advances such as DNA arrays and automated polymerase chain reaction. We are at the threshold of developing a new and more objective as well as rational approach to predict prognosis and response to therapy.

  9. 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

  10. Epigenetic biomarkers in epithelial ovarian cancer.

    PubMed

    Gloss, Brian S; Samimi, Goli

    2014-01-28

    Ovarian cancer is the most lethal gynecological malignancy and the 5th leading cause of cancer death in women. Women with ovarian cancer are typically diagnosed at late stage, when the cancer has spread into the peritoneal cavity and complete surgical removal is difficult. The 5-year survival time for patients diagnosed at this stage is 30%, in contrast to a 5-year survival of 90% for patients diagnosed at early stage. Cancer screening and early detection have the potential to greatly decrease the mortality and morbidity from cancer. The emerging field of epigenetics offers a valuable opportunity to identify cancer-specific DNA methylation changes that can be used in the clinic to improve early-stage diagnosis and better predict response in treated patients. To date, numerous DNA methylation aberrations have been identified in epithelial ovarian cancer; here we review some candidate genes and pathways with potential clinical utility as biomarkers for diagnosis and/or prognosis. It has become clear that even with the great promise of DNA methylation biomarkers in epithelial ovarian cancer, the identification of highly specific, sensitive and robust panels of markers and the standardization of analysis techniques are still required in order to improve detection, treatment and thus patient outcome.

  11. 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

  12. Ovarian Cancer Statistics

    MedlinePlus

    ... at a Glance Show More At a Glance Estimated New Cases in 2016 22,280 % of All New Cancer Cases 1.3% Estimated Deaths in 2016 14,240 % of All Cancer ... of This Cancer : In 2013, there were an estimated 195,767 women living with ovarian cancer in ...

  13. Premature Ovarian Failure

    MedlinePlus

    Premature ovarian failure (POF) is when a woman's ovaries stop working before she is 40. POF is different from premature menopause. With premature menopause, ... be a disease, surgery, chemotherapy, or radiation. With POF, some women still have occasional periods. They may ...

  14. 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

  15. Pleural effusion following ovarian hyperstimulation.

    PubMed

    Junqueira, Jader Joel Machado; Bammann, Ricardo Helbert; Terra, Ricardo Mingarini; Castro, Ana Cristina P; Ishy, Augusto; Fernandez, Angelo

    2012-01-01

    Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic complication that occurs in the luteal phase of an induced hormonal cycle. In most cases, the symptoms are self-limited and spontaneous regression occurs. However, severe cases are typically accompanied by acute respiratory distress. The objective of the present study was to describe the clinical presentation, treatment, and outcome of pleural effusion associated with OHSS in three patients undergoing in vitro fertilization. The patients ranged in age from 27 to 33 years. The onset of symptomatic pleural effusion (bilateral in all cases) occurred, on average, 43 days (range, 27-60 days) after initiation of hormone therapy for ovulation induction. All three patients required hospitalization for massive fluid resuscitation, and two required noninvasive mechanical ventilation. Although all three patients initially underwent thoracentesis, early recurrence of symptoms and pleural effusion prompted the use of drainage with a pigtail catheter. Despite the high output from the pleural drain (mean, 1,000 mL/day in the first week) and prolonged drainage (for 9-22 days), the outcomes were excellent: all three patients were discharged from hospital. Although pleural effusion secondary to OHSS is probably underdiagnosed, the associated morbidity should not be underestimated, especially because it affects potentially pregnant patients. In this study, early diagnosis and appropriate supportive measures yielded favorable results, limiting the surgical approach to adequate pleural drainage.

  16. Anti-PD-L1 prolongs survival and triggers T cell but not humoral anti-tumor immune responses in a human MUC1-expressing preclinical ovarian cancer model.

    PubMed

    Mony, Jyothi Thyagabhavan; Zhang, Lixin; Ma, Tianzhou; Grabosch, Shannon; Tirodkar, Tejas S; Brozick, Joan; Tseng, George; Elishaev, Esther; Edwards, Robert P; Huang, Xin; Vlad, Anda M

    2015-09-01

    Monoclonal antibodies that block inhibitory immune checkpoint molecules and enhance anti-tumor responses show clinical promise in advanced solid tumors. Most of the preliminary evidence on therapeutic efficacy of immune checkpoint blockers comes from studies in melanoma, lung and renal cancer. To test the in vivo potential of programmed death-ligand 1 (PD-L1) blockade in ovarian cancer, we recently generated a new transplantable tumor model using human mucin 1 (MUC1)-expressing 2F8 cells. The MUC1 transgenic (MUC1.Tg) mice develop large number of intraperitoneal (IP) tumors following IP injection of 8 × 10(5) syngeneic 2F8 cells. The tumors are aggressive and display little T cell infiltration. Anti-PD-L1 antibody was administered IP every 2 weeks (200 μg/dose) for a total of three doses. Treatment was started 21 days post-tumor challenge, a time point which corresponds to late tumor stage. The anti-PD-L1 treatment led to substantial T cell infiltration within the tumor and significantly increased survival (p = 0.001) compared to isotype control-treated mice. When the same therapy was administered to wild-type mice challenged with 2F8 tumors, no survival benefit was observed, despite the presence of high titer anti-MUC1 antibodies. However, earlier treatment (day 11) and higher frequency of IP injections restored the T cell responses and led to prolonged survival. Splenocyte profiling via Nanostring using probes for 511 immune genes revealed a treatment-induced immune gene signature consistent with increased T cell-mediated immunity. These findings strongly support further preclinical and clinical strategies exploring PD-L1 blockade in ovarian cancer.

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

    PubMed

    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. 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

  19. 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.

  20. MiR-197 induces Taxol resistance in human ovarian cancer cells by regulating NLK.

    PubMed

    Zou, Dongling; Wang, Dong; Li, Rong; Tang, Ying; Yuan, Li; Long, Xingtao; Zhou, Qi

    2015-09-01

    Chemotherapy is the preferred therapeutic approach for the therapy of advanced ovarian cancer, but 5-year survival rate remains low due to the development of drug resistance. Increasing evidence has documented that microRNAs (miRNAs) act important roles in drug resistance in a variety types of cancer. However, the roles of miRNA in regulating Taxol resistance in ovarian cancer and the detailed mechanism are less reported. We used Taqman probe stem loop real-time PCR to accurately measure the levels of miR-197 in normal ovarian cells, ovarian cancer cells, and Taxol-resistant ovarian cancer cells and found that miR-197 was significantly increased in Taxol-resistant ovarian cancer cells. Enforced expression of miR-197 can promote Taxol resistance, cell proliferation, and invasion of ovarian cancer cells. Meanwhile, repression of miR-197 in ovarian cancer cells can sensitize its response to Taxol and also induced attenuated cell proliferation and invasion ability. Furthermore, investigation of the detailed mechanism showed that the promotion of miR-197 on drug resistance in ovarian cancer cells was partially mediated by downregulating NLK, a negative regulator of WNT signaling pathway. Taken together, our work first demonstrated that miR-197 can confer drug resistance to Taxol, by regulating tumor suppressor, NLK expression in ovarian cancer cells.

  1. Do We Know What Causes Ovarian Cancer?

    MedlinePlus

    ... ovarian cancer be prevented? Do we know what causes ovarian cancer? We don’t yet know exactly what causes ... Another theory is that male hormones (androgens) can cause ovarian cancer. Researchers have made great progress in understanding how ...

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

    ClinicalTrials.gov

    2016-10-10

    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

  3. Adriamycin and cis-platinum in advanced ovarian cancer.

    PubMed

    de Gramont, A; Drolet, Y; Lavoie, A; Painchaud, M; Blouin, R; Tessier, C; Ouellet, P

    1985-06-01

    Forty-eight patients with stage III and IV ovarian epithelial carcinoma were treated with single doses of adriamycin (ADM) 50 mg/m2 and cis-platinum (DDP) 50 mg/m2 every month for nine courses. The pathologically proven response rate was 52.2%, with 22.7% complete response and 29.5% partial response. Median survival was 22 months for all patients, 25 months in stage III and 15 months in stage IV. This study confirms that ADM-DDP is a valuable drug regimen in advanced ovarian carcinoma but further progress is needed to improve the cure rate, which remains low.

  4. Poor ovarian reserve.

    PubMed

    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

  5. 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

  6. Can anti-Müllerian hormone concentrations be used to determine gonadotrophin dose and treatment protocol for ovarian stimulation?

    PubMed

    Fleming, R; Broekmans, F; Calhaz-Jorge, C; Dracea, L; Alexander, H; Nyboe Andersen, A; Blockeel, C; Jenkins, J; Lunenfeld, B; Platteau, P; Smitz, J; de Ziegler, D

    2013-05-01

    The ability to predict the response potential of women to ovarian stimulation may allow the development of individualized ovarian stimulation protocols. This tailored approach to ovarian stimulation could reduce the incidence of ovarian hyperstimulation syndrome in women predicted to have an excessive response to stimulation or could improve pregnancy outcomes in women classed as poor responders. Namely, variation of the type of gonadotrophin-releasing hormone (GnRH) analogue or the form and dosage of gonadotrophin used for stimulation could be adjusted according to an individual's response potential. The serum concentration of anti-Müllerian hormone (AMH) is established as a reliable marker of ovarian reserve, with decreasing concentrations correlated with reduced response potential. This review examines the current evidence evaluating individualized ovarian stimulation protocols using AMH concentration as a predictive marker of ovarian response. The rationale behind why specific treatment protocols based on individual response potential may be more suitable is also discussed. Based on current evidence, it appears that the use of AMH serum concentrations to predict ovarian response and optimize treatment strategies is a promising approach for improving pregnancy outcomes in women undergoing ovarian stimulation. However, prospective randomized controlled trials evaluating this approach are needed before any firm conclusions can be drawn.

  7. Primary Ovarian Insufficiency.

    PubMed

    Laven, Joop S E

    2016-07-01

    Primary ovarian insufficiency (POI), also known as premature ovarian failure or premature menopause, is defined as cessation of menstruation before the expected age of menopause. Potential etiologies for POI can be divided into genetic, autoimmune, and iatrogenic categories. This review will try to summarize the genetic basis of POI focusing on recent data that are available using newer genetic techniques such as genome-wide association studies, whole-exome sequencing (WES), or next-generation sequencing techniques. By using these techniques, many genes have arisen that play some role in the pathophysiology of POI. Some of them have been replicated in other studies; however, the majority has not been proven yet to be unequivocally causative through functional validation studies. Elucidating the genetic and molecular basis of POI is of paramount importance not only in understanding ovarian physiology but also in providing genetic counseling and fertility guidance. Once additional variants are detected, it might become possible to predict the age of (premature) menopause in women at risk for POI. Women having certain perturbations of POI can be offered the option of oocyte cryopreservation, with later thawing and use in assisted reproductive technology at an appropriate age. PMID:27513024

  8. 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

  9. Periodontal bone loss and risk of epithelial ovarian cancer

    PubMed Central

    Babic, Ana; Poole, Elizabeth M.; Terry, Kathryn L.; Cramer, Daniel W.; Teles, Ricardo P.; Tworoger, Shelley S.

    2015-01-01

    Purpose Periodontitis, a chronic inflammatory response to pathogenic bacteria in the oral microbiome, is common among adults. It is associated with several medical conditions, including cardiovascular diseases, and potentially with esophageal, lung, oral and pancreatic cancer. One of the proposed mechanisms behind these associations is systemic inflammation, which has also been implicated in ovarian cancer etiology. The aim of this study was to evaluate association between ovarian cancer and periodontal bone loss. Methods The association between periodontal bone loss, a marker of periodontitis, and risk of epithelial ovarian cancer was estimated among 60,560 participants of the prospective Nurses’ Health Study using Cox proportional hazards analysis. Competing risks analysis was used to estimate association by histological subtype. Results We did not observe an increased risk of ovarian cancer among participants with periodontal bone loss (HR=0.86, 95% CI: 0.64–1.15). Among women younger than 69 years, periodontal bone loss was associated with a 40% (HR=0.60, 95% CI: 0.36–0.98) decreased ovarian cancer risk, while there was no association in women older than 69 (HR=1.09, 95% CI: 0.75–1.58), although this difference did not reach statistical significance (p-heterogeneity=0.06). We observed a suggestive decreased risk for serous tumors (HR=0.76, 95% CI: 0.53–1.09). The number of natural teeth and root canals, other metrics of oral health, were not associated with ovarian cancer risk. Conclusion Our results do not support an increased ovarian cancer risk in women with periodontal bone loss, however there was a significant decrease in risk in women younger than 69. Given the unexpected association between periodontal bone loss and ovarian cancer risk in younger women, further research is warranted. PMID:25837263

  10. Protection of ovarian function during chemotherapy for ovarian cancer.

    PubMed

    Tianmin, X; Weiqin, C; Shuying, W; Yang, L; Manhua, C

    2014-01-01

    The protection of ovarian function during chemotherapy is an urgent issue to be resolved after the fertility preserving surgery on patients with ovarian cancer. The paper summarizes and analyzes the research progress on the protective measures in the aspects of gonadotropin releasing hormone analogue (GnRHa), cell protecting agents, and traditional Chinese medical science and drugs.

  11. Mayo Clinic experience with epithelial ovarian cancer.

    PubMed

    Decker, D G

    1983-08-01

    Clinical investigation of epithelial ovarian cancer must involve the precise definition of the lesion, careful application of new techniques, the objective evaluation of such techniques, the comparison of results in a randomized fashion with prior forms of therapy, careful pathological evaluation of the tumour, and the evaluation of toxicity to the patient. The interdisciplinary team approach to the treatment of epithelial ovarian cancer and the development of randomized, prospective trials are essential. Utilizing these two elements, a better integration of surgery, chemotherapy and radiation therapy can be accomplished. Of great importance is the evaluation of response patterns by an observer who is skilled in pelvic examinations and familiar with the natural history of epithelial ovarian cancer. The increasingly important role of surgery in the treatment of this cancer is now more clearly defined. The psychological effects of chemotherapy as well as the response patterns to chemotherapy must be evaluated. During the past 20 years, considerable progress has been made in prolonging the useful, functional life of the patient. The ultimate cure is still a matter for the future and is predicated on more effective combinations of potent chemotherapeutic combinations and a clearer definition of the role of radiation therapy.

  12. Dysregulated estrogen receptor signaling in the hypothalamic-pituitary-ovarian axis leads to ovarian epithelial tumorigenesis in mice.

    PubMed

    Laws, Mary J; Kannan, Athilakshmi; Pawar, Sandeep; Haschek, Wanda M; Bagchi, Milan K; Bagchi, Indrani C

    2014-03-01

    The etiology of ovarian epithelial cancer is poorly understood, mainly due to the lack of an appropriate experimental model for studying the onset and progression of this disease. We have created a mutant mouse model in which aberrant estrogen receptor alpha (ERα) signaling in the hypothalamic-pituitary-ovarian axis leads to ovarian epithelial tumorigenesis. In these mice, termed ERαd/d, the ERα gene was conditionally deleted in the anterior pituitary, but remained intact in the hypothalamus and the ovary. The loss of negative-feedback regulation by estrogen (E) at the level of the pituitary led to increased production of luteinizing hormone (LH) by this tissue. Hyperstimulation of the ovarian cells by LH resulted in elevated steroidogenesis, producing high circulating levels of steroid hormones, including E. The ERαd/d mice exhibited formation of palpable ovarian epithelial tumors starting at 5 months of age with 100% penetrance. By 15 months of age, 80% of ERαd/d mice die. Besides proliferating epithelial cells, these tumors also contained an expanded population of luteinized stromal cells, which acquire the ability to express P450 aromatase and synthesize E locally. In response to the elevated levels of E, the ERα signaling was accentuated in the ovarian epithelial cells of ERαd/d mice, triggering increased ERα-dependent gene expression, abnormal cell proliferation, and tumorigenesis. Consistent with these findings, treatment of ERαd/d mice with letrozole, an aromatase inhibitor, markedly reduced circulating E and ovarian tumor volume. We have, therefore, developed a unique animal model, which serves as a useful tool for exploring the involvement of E-dependent signaling pathways in ovarian epithelial tumorigenesis.

  13. 40 CFR 51.354 - Adequate tools and resources.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 2 2013-07-01 2013-07-01 false Adequate tools and resources. 51.354... Requirements § 51.354 Adequate tools and resources. (a) Administrative resources. The program shall maintain the administrative resources necessary to perform all of the program functions including...

  14. 40 CFR 51.354 - Adequate tools and resources.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 2 2014-07-01 2014-07-01 false Adequate tools and resources. 51.354... Requirements § 51.354 Adequate tools and resources. (a) Administrative resources. The program shall maintain the administrative resources necessary to perform all of the program functions including...

  15. 40 CFR 51.354 - Adequate tools and resources.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 2 2012-07-01 2012-07-01 false Adequate tools and resources. 51.354... Requirements § 51.354 Adequate tools and resources. (a) Administrative resources. The program shall maintain the administrative resources necessary to perform all of the program functions including...

  16. 13 CFR 108.200 - Adequate capital for NMVC Companies.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... VENTURE CAPITAL (âNMVCâ) PROGRAM Qualifications for the NMVC Program Capitalizing A Nmvc Company § 108.200 Adequate capital for NMVC Companies. You must meet the requirements of §§ 108.200-108.230 in order to... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Adequate capital for...

  17. 34 CFR 200.20 - Making adequate yearly progress.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 34 Education 1 2012-07-01 2012-07-01 false Making adequate yearly progress. 200.20 Section 200.20... Basic Programs Operated by Local Educational Agencies Adequate Yearly Progress (ayp) § 200.20 Making... State data system; (vi) Include, as separate factors in determining whether schools are making AYP for...

  18. 34 CFR 200.20 - Making adequate yearly progress.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 34 Education 1 2013-07-01 2013-07-01 false Making adequate yearly progress. 200.20 Section 200.20... Basic Programs Operated by Local Educational Agencies Adequate Yearly Progress (ayp) § 200.20 Making... State data system; (vi) Include, as separate factors in determining whether schools are making AYP for...

  19. 34 CFR 200.20 - Making adequate yearly progress.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Making adequate yearly progress. 200.20 Section 200.20... Basic Programs Operated by Local Educational Agencies Adequate Yearly Progress (ayp) § 200.20 Making... State data system; (vi) Include, as separate factors in determining whether schools are making AYP for...

  20. 34 CFR 200.20 - Making adequate yearly progress.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 34 Education 1 2014-07-01 2014-07-01 false Making adequate yearly progress. 200.20 Section 200.20... Basic Programs Operated by Local Educational Agencies Adequate Yearly Progress (ayp) § 200.20 Making... State data system; (vi) Include, as separate factors in determining whether schools are making AYP for...

  1. 34 CFR 200.20 - Making adequate yearly progress.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 1 2011-07-01 2011-07-01 false Making adequate yearly progress. 200.20 Section 200.20... Basic Programs Operated by Local Educational Agencies Adequate Yearly Progress (ayp) § 200.20 Making... State data system; (vi) Include, as separate factors in determining whether schools are making AYP for...

  2. 9 CFR 305.3 - Sanitation and adequate facilities.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Sanitation and adequate facilities. 305.3 Section 305.3 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF... OF VIOLATION § 305.3 Sanitation and adequate facilities. Inspection shall not be inaugurated if...

  3. 9 CFR 305.3 - Sanitation and adequate facilities.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Sanitation and adequate facilities. 305.3 Section 305.3 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF... OF VIOLATION § 305.3 Sanitation and adequate facilities. Inspection shall not be inaugurated if...

  4. 40 CFR 51.354 - Adequate tools and resources.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 2 2011-07-01 2011-07-01 false Adequate tools and resources. 51.354... Requirements § 51.354 Adequate tools and resources. (a) Administrative resources. The program shall maintain the administrative resources necessary to perform all of the program functions including...

  5. 40 CFR 51.354 - Adequate tools and resources.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 2 2010-07-01 2010-07-01 false Adequate tools and resources. 51.354... Requirements § 51.354 Adequate tools and resources. (a) Administrative resources. The program shall maintain the administrative resources necessary to perform all of the program functions including...

  6. 13 CFR 107.200 - Adequate capital for Licensees.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Adequate capital for Licensees. 107.200 Section 107.200 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION SMALL BUSINESS INVESTMENT COMPANIES Qualifying for an SBIC License Capitalizing An Sbic § 107.200 Adequate capital...

  7. 21 CFR 201.5 - Drugs; adequate directions for use.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Drugs; adequate directions for use. 201.5 Section 201.5 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL LABELING General Labeling Provisions § 201.5 Drugs; adequate directions for use....

  8. 21 CFR 201.5 - Drugs; adequate directions for use.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 4 2011-04-01 2011-04-01 false Drugs; adequate directions for use. 201.5 Section 201.5 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL LABELING General Labeling Provisions § 201.5 Drugs; adequate directions for use....

  9. 7 CFR 4290.200 - Adequate capital for RBICs.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Adequate capital for RBICs. 4290.200 Section 4290.200 Agriculture Regulations of the Department of Agriculture (Continued) RURAL BUSINESS-COOPERATIVE SERVICE AND... Qualifications for the RBIC Program Capitalizing A Rbic § 4290.200 Adequate capital for RBICs. You must meet...

  10. Can Ovarian Cancer Be Prevented?

    MedlinePlus

    ... ovaries removed with your doctor. Prevention strategies for women with a family history of ovarian cancer or BRCA mutation If your ... what the results mean to you. For some women with a strong family history of ovarian cancer, knowing they do not have ...

  11. Quantifying variability within water samples: the need for adequate subsampling.

    PubMed

    Donohue, Ian; Irvine, Kenneth

    2008-01-01

    Accurate and precise determination of the concentration of nutrients and other substances in waterbodies is an essential requirement for supporting effective management and legislation. Owing primarily to logistic and financial constraints, however, national and regional agencies responsible for monitoring surface waters tend to quantify chemical indicators of water quality using a single sample from each waterbody, thus largely ignoring spatial variability. We show here that total sample variability, which comprises both analytical variability and within-sample heterogeneity, of a number of important chemical indicators of water quality (chlorophyll a, total phosphorus, total nitrogen, soluble molybdate-reactive phosphorus and dissolved inorganic nitrogen) varies significantly both over time and among determinands, and can be extremely high. Within-sample heterogeneity, whose mean contribution to total sample variability ranged between 62% and 100%, was significantly higher in samples taken from rivers compared with those from lakes, and was shown to be reduced by filtration. Our results show clearly that neither a single sample, nor even two sub-samples from that sample is adequate for the reliable, and statistically robust, detection of changes in the quality of surface waters. We recommend strongly that, in situations where it is practicable to take only a single sample from a waterbody, a minimum of three sub-samples are analysed from that sample for robust quantification of both the concentrations of determinands and total sample variability. PMID:17706740

  12. 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

  13. A review of the cutaneous paraneoplastic associations and metastatic presentations of ovarian carcinoma.

    PubMed

    Scheinfeld, N

    2008-01-01

    Ovarian carcinoma possesses cutaneous and paraneoplastic associations. The aim of this study was to review the paraneoplastic associations and metastatic presentations of ovarian carcinoma. PubMed was searched through December 2006 for references to cutaneous metastatic ovarian carcinoma (CMOC). CMOC occurs in 2-7% of cases, manifests in advanced disease and indicates a poor prognosis. The paraneoplastic associations of ovarian carcinoma include acanthosis nigricans, Raynaud's phenomenon, scleroderma, dermatomyositis and palmar fasciitis with polyarthritis. Dermatomyositis, in particular, can precede the diagnosis of ovarian carcinoma. Ovarian carcinoma has many cutaneous paraneoplastic effects and metastatic presentations, all of which portend a poor prognosis. Dermatomyositis is sometimes the initial manifestation of ovarian cancer, thus women > 40 years of age with dermatomyositis should be checked for ovarian carcinoma. It is possible that paraneoplastic dermtomyosititis can be distinguished from nonparaneoplastic dermatomyostitis by the former's lack of (i) associated Raynaud's phenomenon, (ii) response to treatment, (iii) autoantibodies, (iv) overlap and association with other collagen vascular diseases and (v) the presence of the prodromal symptoms of ovarian carcinoma such as gastrointestinal symptoms, urinary symptoms and/or fatigue or malaise.

  14. Ovarian disorders in domestic animals.

    PubMed Central

    MacLachlan, N J

    1987-01-01

    The histologic appearance of the ovaries and persistence of corpora lutea vary considerably among domestic animals, particularly between spontaneous and induced ovulators. The seasonally polyestrous mare has a variety of unique characteristics in ovarian structure and general reproductive function. Among the anomalies of ovarian development is the bovine freemartin with gonads containing a mixture of male and female elements. A variety of ovarian cysts occur in domestic animals, and persistent corpora lutea with associated reproductive perturbations occur in several species. Ovarian tumors are relatively uncommon in domestic animals, with most examples described in dogs, cats, and horses. These ovarian neoplasms are generally classified as epithelial, germ cell, or sex cord-stromal tumors. PMID:3665869

  15. Puberty, ovarian steroids, and stress.

    PubMed

    Young, Elizabeth A; Altemus, Margaret

    2004-06-01

    Puberty is accompanied by a number of changes, among them increased risk for development of major depression. The most common etiology of major depression is stressful life events, being present in approximately 90% of first episodes of depression. The hypothalamic-pituitary-adrenal (HPA) axis is one of the major systems involved in responses to stress, and this system is clearly influenced by ovarian hormones. Normal women demonstrate resistance to negative feedback of both cortisol in the fast-feedback paradigm and dexamethasone in the standard delayed-feedback paradigm. Depressed premenopausal women show greater increases in baseline cortisol than postmenopausal depressed women and than depressed men. Studies in rodents suggest a similar resistance to glucocorticoid feedback but suggest that estradiol can function to inhibit stress responsiveness. Studies of premenopausal depressed women demonstrate lower estradiol, which suggests that there is less inhibitory feedback of estradiol on the HPA axis, while normal progesterone continues to augment stress responses further. The onset of these reproductive hormonal changes modulating stress systems at puberty may sensitize girls to stressful life events, which become more frequent at the transition to puberty and young adulthood.

  16. Ovarian follicular growth and maturity and follicular production of progesterone and oestradiol in response to porcine luteinising hormone and porcine follicle stimulating hormone in albino (S*AS) hens in vivo and in vitro.

    PubMed

    Su, H; Silversides, F G; Villeneuve, P

    1999-09-01

    The effects of the SAS gene on follicular growth were studied by feeding Sudan IV and Sudan Black B, on follicular maturity by measuring P4 and E2 output of the 5 largest follicles (F1 to F5) in vitro, and on ovarian response (plasma progesterone, P4, and oestradiol, E2) to administration of porcine follicle-stimulating hormone (pFSH) and porcine luteinising hormone (pLH) in old laying hens. Albino hens had fewer dye rings in the yolks of their eggs than non-albinos (8.32 compared to 8.59) and the yolks from albinos weighed less. The numbers of normal and atretic follicles larger than 3 mm in diameter did not differ between the two genotypes. The P4 outputs from the F1 and F2 follicles were significantly greater for albino hens, but P4 production of other follicles was not different for the two genotypes. The P4 output of the F1 follicle in response to pLH was dose-dependent and greater for albino hens than for non-albinos. Porcine LH did not increase the follicular E2 output in either genotype. Administration of pLH, but not pFSH, increased plasma P4 and E2 concentrations, with no difference between genotypes. These data suggest that the F1 follicles for albino hens are precocious, resulting in a reduced growth period and a smaller weight at ovulation.

  17. Interleukin-1 deficiency prolongs ovarian lifespan in mice

    PubMed Central

    Uri-Belapolsky, Shiri; Shaish, Aviv; Eliyahu, Efrat; Grossman, Hadas; Levi, Mattan; Chuderland, Dana; Ninio-Many, Lihi; Hasky, Noa; Shashar, David; Almog, Tal; Kandel-Kfir, Michal; Harats, Dror; Shalgi, Ruth; Kamari, Yehuda

    2014-01-01

    Oocyte endowment dwindles away during prepubertal and adult life until menopause occurs, and apoptosis has been identified as a central mechanism responsible for oocyte elimination. A few recent reports suggest that uncontrolled inflammation may adversely affect ovarian reserve. We tested the possible role of the proinflammatory cytokine IL-1 in the age-related exhaustion of ovarian reserve using IL-1α and IL-1β–KO mice. IL-1α–KO mice showed a substantially higher pregnancy rate and litter size compared with WT mice at advanced age. The number of secondary and antral follicles was significantly higher in 2.5-mo-old IL-1α–KO ovaries compared with WT ovaries. Serum anti-Müllerian hormone, a putative marker of ovarian reserve, was markedly higher in IL-1α–KO mice from 2.5 mo onward, along with a greater ovarian response to gonadotropins. IL-1β–KO mice displayed a comparable but more subtle prolongation of ovarian lifespan compared with IL-1α–KO mice. The protein and mRNA of both IL-1α and IL-1β mice were localized within the developing follicles (oocytes and granulosa cells), and their ovarian mRNA levels increased with age. Molecular analysis revealed decreased apoptotic signaling [higher B-cell lymphoma 2 (BCL-2) and lower BCL-2–associated X protein levels], along with a marked attenuation in the expression of genes coding for the proinflammatory cytokines IL-1β, IL-6, and TNF-α in ovaries of IL-1α–KO mice compared with WT mice. Taken together, IL-1 emerges as an important participant in the age-related exhaustion of ovarian reserve in mice, possibly by enhancing the expression of inflammatory genes and promoting apoptotic pathways. PMID:25114230

  18. 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

  19. 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

  20. 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.

  1. Ovarian programming and GIFT.

    PubMed

    Rolet, F; Gadaud, S; Zorn, J R; Boyer, P; Guichard, A; Cedard, L

    1988-05-01

    The procedures used for programming and ovarian stimulation in GIFT are identical to those used for in-vitro fertilization. At the Baudelocque Hospital, the hypophyseal gonadal axis is suppressed by administering a gonadotrophin-releasing hormone analogue (Decapeptyl, D-Trp-6-LHRH). Programming for the week of GIFT is then possible by controlling three stages: the beginning of treatment, which is independent of the date of the patient's period, the duration of treatment, which has 5 days' maximum variation, and an end-point of suppressing the spontaneous LH surge.

  2. 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

  3. 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. PMID:25089903

  4. 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

  5. "Incessant ovulation" and ovarian cancer.

    PubMed

    Casagrande, J T; Louie, E W; Pike, M C; Roy, S; Ross, R K; Henderson, B E

    1979-07-28

    A case-control study of 150 ovarian cancer patients under the age of 50 and individually matched controls was done to study the influence of fertility and oral contraceptive use on the risk of ovarian cancer. The risk decreased with increasing numbers of live births, with increasing numbers of incomplete pregnancies, and with the use of oral contraceptives. These three factors can be amalgamated into a single index of protection--"protected time"--by considering them all as periods of anovulation. The complement of protected time--viz., "ovulatory age", the period between menarche and diagnosis of ovarian cancer (or cessation of menses) minus "protected time"--was strongly related to risk of ovarian cancer. Other factors found to be associated with increased ovarian cancer risk were obesity, cervical polyps, and gallbladder disease. Women who had an "immediate" intolerance to oral contraceptive use had a fourfold increased risk of ovarian cancer. 7 patients, but no controls, could recall a family history of ovarian cancer.

  6. The epidemiology of ovarian cancer.

    PubMed

    Tortolero-Luna, G; Mitchell, M F

    1995-01-01

    Ovarian cancer is the second most common cancer of the female reproductive system and the leading cause of death from gynecologic malignancies. In 1995, 26,600 women will be diagnosed with ovarian cancer in the U.S., and 14,500 women will die from the disease. Between 1986-1900, the overall age-adjusted incidence was 14.3/100,000 women; mortality was 7.8/100,000 women. Ovarian cancer, rare before age 40, increases steeply thereafter and peaks at ages 65-75. Incidence and mortality rates are higher among white women than among African-American women. Over the last three decades, ovarian cancer incidence has remained stable in high-risk countries, while an increasing trend has been reported in low-risk countries. Despite recent advancements in treatment, the overall five-year survival rates continues to be low (39%). Over 70% of ovarian tumors are diagnosed when regional or distant involvement has already occurred, causing survival rates to remain stable. The etiology of ovarian cancer is poorly understood. Most studies have focused on the epidemiology of invasive epithelial ovarian tumors, while few have explored the epidemiology of epithelial tumors of low malignant potential and nonepithelial tumors. Factors associated with an increased risk for invasive epithelial ovarian cancer include age, race, nulliparity, family history of ovarian cancer, and history of endometrial or breast cancer. Factors associated with a reduced risk are history of one or more full-term pregnancies, use of oral contraceptives, history of breast feeding, tubal ligation, and hysterectomy. Other factors such as infertility drugs, hormone replacement therapy, age at menarche, age at menopause, dietary factors, lactose intolerance, talc use, coffee and alcohol consumption have been suggested, but their role is still inconclusive.

  7. 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

  8. Maturation of ovarian follicles in the prepubertal gilt.

    PubMed

    Christenson, R K; Ford, J J; Redmer, D A

    1985-01-01

    The processes of follicle development and puberty are closely related, and both are associated with maturation of the hypothalamic-pituitary-ovarian axis. Prenatal development of the ovary is independent of gonadotrophic stimulation. Beyond 60 days of age (postnatally), tertiary follicles develop and gonadotrophins begin to influence ovarian follicular development. Negative feedback regulation of pituitary gonadotrophins by ovarian secretions develops between 60 and 100 days of age. In the prepubertal gilt, no consistent changes in peripheral FSH, oestrogen or progesterone concentrations have been identified which are associated with recruitment of the first set of preovulatory follicles. Whether LH secretion increases before this recruitment remains equivocal. Few details are available on how gonadotrophic hormones stimulate ovarian function in the prepubertal gilt. On the basis of a follicular maturation model that has been described for the rat, the actions of FSH, LH and oestrogens on follicular cell receptors and the regulation of aromatase activity seem paramount. Aromatization of androgens to oestrogens has been proposed as a central regulator for follicular maturation. In the prepubertal gilt, a selective increase in peripheral FSH concentration occurs on Day 1 after unilateral ovariectomy, followed by significant increases in ovarian venous concentrations of oestradiol and inhibin on Days 2 and 4 and compensatory growth as measured by follicular fluid volume on Days 2, 4 and 8. Administration of pig follicular fluid to the prepubertal gilt during and after unilateral ovariectomy suppresses compensatory ovarian hypertrophy by mechanisms yet to be determined. In pigs a number of intraovarian factors have been identified, but there is little information on how these factors regulate follicular recruitment and growth. The factor(s) that prevents ovarian follicles in the prepubertal gilt from progressing to ovulation after acquiring the ability to ovulate in

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

    PubMed Central

    Hiss, Donavon

    2012-01-01

    The hallmarks of ovarian cancer encompass the development of resistance, disease recurrence and poor prognosis. Ovarian cancer cells express gene signatures which pose significant challenges for cancer drug development, therapeutics, prevention and management. Despite enhancements in contemporary tumor debulking surgery, tentative combination regimens and abdominal radiation which can achieve beneficial response rates, the majority of ovarian cancer patients not only experience adverse effects, but also eventually relapse. Therefore, additional therapeutic possibilities need to be explored to minimize adverse events and prolong progression-free and overall response rates in ovarian cancer patients. Currently, a revival in cancer drug discovery is devoted to identifying diagnostic and prognostic ovarian cancer biomarkers. However, the sensitivity and reliability of such biomarkers may be complicated by mutations in the BRCA1 or BRCA2 genes, diverse genetic risk factors, unidentified initiation and progression elements, molecular tumor heterogeneity and disease staging. There is thus a dire need to expand existing ovarian cancer therapies with broad-spectrum and individualized molecular targeted approaches. The aim of this review is to profile recent developments in our understanding of the interrelationships among selected ovarian tumor biomarkers, heterogeneous expression signatures and related molecular signal transduction pathways, and their translation into more efficacious targeted treatment rationales. PMID:22481932

  10. Prediction of Postchemotherapy Ovarian Function Using Markers of Ovarian Reserve

    PubMed Central

    Xia, Rong; Schott, Anne F.; McConnell, Daniel; Banerjee, Mousumi; Hayes, Daniel F.

    2014-01-01

    Background. Reproductive-aged women frequently receive both chemotherapy and endocrine therapy as part of their treatment regimen for early stage hormone receptor-positive breast cancer. Chemotherapy results in transient or permanent ovarian failure in the majority of women. The difficulty in determining which patients will recover ovarian function has implications for adjuvant endocrine therapy decision making. We hypothesized that pretreatment serum anti-Müllerian hormone (AMH) and inhibin B concentrations would predict for ovarian function following chemotherapy. Methods. Pre- and perimenopausal women aged 25–50 years with newly diagnosed breast cancer were enrolled. Subjects underwent phlebotomy for assessment of serum AMH, inhibin B, follicle-stimulating hormone, and estradiol prior to chemotherapy and 1 month and 1 year following completion of treatment. Associations among hormone concentrations, clinical factors, and biochemically assessed ovarian function were assessed. Results. Twenty-seven subjects were evaluable for the primary endpoint. Median age was 41. Twenty subjects (74.1%) experienced recovery of ovarian function within 18 months. Of the 26 evaluable subjects assessed prior to chemotherapy, 19 (73.1%) had detectable serum concentrations of AMH. The positive predictive value of a detectable baseline serum AMH concentration for recovery of ovarian function was 94.7%, and the negative predictive value was 85.7%. On univariate analysis, younger age and detectable serum AMH concentration at chemotherapy initiation were predictive of increased likelihood of recovery of ovarian function. Conclusion. Prechemotherapy assessment of serum AMH may be useful for predicting postchemotherapy ovarian function. This finding has implications for decision making about adjuvant endocrine therapy in premenopausal women treated with chemotherapy. PMID:24319018

  11. Possible role of ovarian epithelial inflammation in ovarian cancer.

    PubMed

    Ness, R B; Cottreau, C

    1999-09-01

    Ovarian cancer is a commonly fatal disease for which prevention strategies have been limited, in part because of a lack of understanding of the underlying biology. This paper reviews the epidemiologic literature in the English language on risk factors and protective factors for ovarian cancer and proposes a novel hypothesis that a common mechanism underlying this disease is inflammation. Previous hypotheses about the causes of ovarian cancer have attributed risk to an excess number of lifetime ovulations or to elevations in steroid hormones. Inflammation may underlie ovulatory events because an inflammatory reaction is induced during the process of ovulation. Additional risk factors for ovarian cancer, including asbestos and talc exposure, endometriosis (i.e., ectopic implantation of uterine lining tissue), and pelvic inflammatory disease, cannot be directly linked to ovulation or to hormones but do cause local pelvic inflammation. On the other hand, tubal ligation and hysterectomy act as protective factors, perhaps by diminishing the likelihood that the ovarian epithelium will be exposed to environmental initiators of inflammation. Inflammation entails cell damage, oxidative stress, and elevations of cytokines and prostaglandins, all of which may be mutagenic. The possibility that inflammation is a pathophysiologic contributor to the development of ovarian cancer suggests a directed approach to future research

  12. Ovarian hyperstimulation syndrome

    PubMed Central

    Kumar, Pratap; Sait, Sameer Farouk; Sharma, Alok; Kumar, Mukesh

    2011-01-01

    Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic complication of assisted reproduction technology. The syndrome is characterized by cystic enlargement of the ovaries and a fluid shift from the intravascular to the third space due to increased capillary permeability and ovarian neoangiogenesis. Its occurrence is dependent on the administration of human chorionic gonadotrophin (hCG). β-hCG and its analogs, estrogen, estradiol, prolactin, histamine and prostaglandins have all been implicated in OHSS but now it is increasingly better understood that the vasoactivesubstances such as interleukins, tumor necrosis factor-α, endothelin-1, and vascular endothelial growth factor (VEGF) secreted by the ovaries have been implicated in increasing vascular permeability. Enlargement of the ovaries causes abdominal pain, nausea and vomiting. Leakage of fluid from follicles, increased capillary permeability leading to third spacing (due to the release of vasoactive substances), or frank rupture of follicles can all cause ascites. Due to leakage of fluid through the impaired blood vessels both within and outside the ovary there is massive fluid-shift from the intra-vescular bed to the third compartment results in intravascular hypovolemia with concomitant development of edema, ascites, hydrothorax and/or hydropericardium. Low-dose gonadotrophin protocols have been implemented to reduce the risks of fertility treatment in polycystic ovary syndrome patients. Prophylactic albumin administration may interrupt the development of OHSS by increasing the plasma oncotic pressure and binding mediators of ovarian origin. OHSS is significantly lower in an antagonist protocol than in an agonist protocol. Cabergoline inhibits partially the VEGF receptor 2 phosphorylation levels and associated vascular permeability without affecting luteal angiogenesis reduces the ‘early’ (within the first 9 days after hCG) onset of OHSS. To prevent thrombosis, subcutaneous heparin 5000-7500 U/d is

  13. Aberrant Lipid Metabolism: An Emerging Diagnostic and Therapeutic Target in Ovarian Cancer

    PubMed Central

    Pyragius, Carmen E.; Fuller, Maria; Ricciardelli, Carmela; Oehler, Martin K.

    2013-01-01

    Ovarian cancer remains the most lethal gynaecological cancer. A better understanding of the molecular pathogenesis of ovarian cancer is of critical importance to develop early detection tests and identify new therapeutic targets that would increase survival. Cancer cells depend on de novo lipid synthesis for the generation of fatty acids to meet the energy requirements for increased tumour growth. There is increasing evidence that lipid metabolism is deregulated in cancers, including ovarian cancer. The increased expression and activity of lipogenic enzymes is largely responsible for increased lipid synthesis, which is regulated by metabolic and oncogenic signalling pathways. This article reviews the latest knowledge on lipid metabolism and the alterations in the expression of lipogenic enzymes and downstream signalling pathways in ovarian cancer. Current developments for exploiting lipids as biomarkers for the detection of early stage ovarian cancer and therapeutic targets are discussed. Current research targeting lipogenic enzymes and lipids to increase the cytotoxicity of chemotherapy drugs is also highlighted. PMID:23574936

  14. 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

  15. A rare benign ovarian tumour.

    PubMed

    Palmeiro, Marta Morna; Cunha, Teresa Margarida; Loureiro, Ana Luisa; Esteves, Gonçalo

    2016-01-01

    Sclerosing stromal tumour (SST) of the ovary is an extremely rare and benign ovarian neoplasm, accounting for 6% of the sex cord stromal ovarian tumours subtype. Usually, it is found during the second and third decades of life. Patients commonly present with pelvic pain, a palpable pelvic mass or menstrual irregularity. We report a case of a 20-year-old woman reporting of mild pelvic pain, with normal laboratory data. On imaging examinations, a large right adnexal tumour was found, with features suggesting an ovarian sex cord tumour. The patient underwent right salpingo-oophorectomy, diagnosing a SST of the ovary. This paper also reviews the literature, and emphasises the typical pathological and imaging characteristics of these rare benign ovarian lesions, and their impact, in a conservative surgery. PMID:26933186

  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. Gedunin, a novel natural substance, inhibits ovarian cancer cell proliferation.

    PubMed

    Kamath, Siddharth G; Chen, Ning; Xiong, Yin; Wenham, Robert; Apte, Sachin; Humphrey, Marcia; Cragun, Janiel; Lancaster, Johnathan M

    2009-12-01

    The discovery of more active therapeutic compounds is essential if the outcome for patients with advanced-stage epithelial ovarian cancer is to be improved. Gedunin, an extract of the neem tree, has been used as a natural remedy for centuries in Asia. Recently, gedunin has been shown to have potential in vitro antineoplastic properties; however, its effect on ovarian cancer cells is unknown. We evaluated the in vitro effect of gedunin on SKOV3, OVCAR4, and OVCAR8 ovarian cancer cell lines proliferation, alone and in the presence of cisplatin. Furthermore, we analyzed in vitro gedunin sensitivity data, integrated with genome-wide expression data from 54 cancer cell lines in an effort to identify genes and molecular pathways that underlie the mechanism of gedunin action. In vitro treatment of ovarian cancer cell lines with gedunin alone produced up to an 80% decrease in cell proliferation (P < 0.01) and, combining gedunin with cisplatin, demonstrated up to a 47% (P < 0.01) decrease in cell proliferation compared with cisplatin treatment alone. Bioinformatic analysis of integrated gedunin sensitivity and gene expression data identified 52 genes to be associated with gedunin sensitivity. These genes are involved in molecular functions related to cell cycle control, carcinogenesis, lipid metabolism, and molecular transportation. We conclude that gedunin has in vitro activity against ovarian cancer cells and, further, may enhance the antiproliferative effect of cisplatin. The molecular determinants of in vitro gedunin response are complex and may include modulation of cell survival and apoptosis pathways. PMID:19955938

  18. Dihydroartiminisin inhibits the growth and metastasis of epithelial ovarian cancer.

    PubMed

    Wu, Buchu; Hu, Ke; Li, Shu; Zhu, Jing; Gu, Liying; Shen, Haoran; Hambly, Brett D; Bao, Shisan; Di, Wen

    2012-01-01

    Dihydroartiminisin (DHA), the active component of a Chinese herb (Artemisia annua), has been utilised as an anti-malarial drug since ancient China. DHA has also been shown to inhibit proliferation of cancer in vitro. However, the capacity of DHA to inhibit the development of ovarian cancer is still unclear. The adhesion, invasion, and migration of human ovarian cancer cell line (HO8910PM) was determined following DHA treatment in vitro, using Matrigel coated plate, transwell membrane chamber, and wound healing models, respectively. A mouse ovarian cancer model was established by orthotopic inoculation of HO8910PM cell line in nude mice. The growth and metastasis in vivo was determined 8 weeks post-implantation in response to DHA treatment. The expression of phosphorylated focal adhesion kinase (pFAK) and matrix metalloproteinases (MMP-2 and MMP-9) was evaluated using Western blotting. The expression of Von Willebrand factor (vWF) and infiltration of macrophages were determined, using immunohistochemistry. DHA inhibits ovarian cancer cell proliferation, adhesion, migration and invasion in vitro in a dose-dependent manner, consistent with decreased expression of pFAK and MMP-2, but not MMP-9. DHA inhibited metastasis significantly in vivo, associated with reduced vWF expression and macrophage infiltration. In conclusion, DHA inhibits the development of ovarian cancer, in part via down-regulating pFAK, MMP-2, vWF and macrophage infiltration. PMID:22025319

  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

    2016-09-26

    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. 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.

  1. Recurrent ovarian cancer.

    PubMed

    Pujade-Lauraine, E; Combe, P

    2016-04-01

    Recurrence still occurs in a majority of patients with advanced ovarian cancer. However, progress in the management has allowed a significant prolongation of survival for relapsing disease. These last years, the field of interest has moved from chemotherapy to targeted therapy which is dominated by anti-angiogenic and anti-PARP agents. It is assumed that platinum-free interval will not remain the main prognostic and predictive criterion in the future, and will be replaced by a multi-factorial approach. This trend for personalization of therapy has highlighted important neglected fields for clinical research such as multi-line (≥3) relapse, frail patients including elderly and symptomatic and supportive measures. PMID:27141075

  2. 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.

  3. Premature ovarian failure.

    PubMed

    Vujović, Svetlana; Ivović, Miomira; Tancić-Gajić, Milina; Marina, Ljiljana; Barać, Marija; Arizanović, Zorana; Nenezić, Ana; Ivanisević, Maja; Micić, Jelena; Sajić, Silvija; Micić, Dragan

    2012-01-01

    Premature ovarian failure (POF) is the occurrence of hypergonadotropic hypoestrogenic amenorrhea in women under the age of forty years. It is idiopathic in 74-90% patients. Known cases can be divided into primary and secondary POF. In primary POF genetic aberrations can involve the X chromosome (monosomy, trisomy, translocations, deletions) or autosomes. Genetic mechanisms include reduced gene dosage and non-specific chromosome effects impairing meiosis, decreasing the pool of primordial follicles and increasing atresia due to apoptosis or failure of follicle maturation. Autoimmune ovarian damage is caused by alteration of T-cell subsets and T-cell mediated injury, increase of autoantibody producing B-cells, a low number of effector/cytotoxic lymphocyte, which decreases the number and activity of natural killer cells. Bilateral oophorectomy, chemotherapy, radiotherapy and infections cause the secondary POF. Symptoms of POF include irritability, nervousness, loss of libido, depression, lack of concentration, hot flushes, weight gaining, dry skin, vaginal dryness, frequent infections etc.The diagnosis is confirmed by the level of FSH of over 40 IU/L and estradiol below 50 pmol/L in women aged below 40 years. Biochemical and other hormonal analysis (free thyroxin, TSH, prolactin, testosterone), karyotype (<30 years of age), ultrasound of the breasts and pelvis are advisable. Optimal therapy is combined estrogen progestagen therapy given in a sequential rhythm, after excluding absolute contraindications. Testosterone can be added to adnexectomized women and those with a low libido. Sequential estrogen progestagen replacement therapy is the first line therapy for ovulation induction in those looking for pregnancy and after that oocyte donation will be advised. Appropriate estro-progestagen therapy improves the quality of life and prevents complications such as cardiovascular diseases, osteoporosis, stroke etc. PMID:23350261

  4. [Premature ovarian failures].

    PubMed

    Bricaire, Léopoldine; Laroche, Emmanuelle; Bourcigaux, Nathalie; Donadille, Bruno; Christin-Maitre, Sophie

    2013-11-01

    Premature ovarian failure (POF) is clinically suspected by amenorrhea and confirmed by an elevated FSH serum level above 40 mUI/L (even 20 mUI/L) twice, in a woman before the age of 40. Prevalence of POF is between 1 to 2% in women. In 90% of cases, no aetiology is identified. Obvious causes are chemotherapy, pelvic radiotherapy, ovarian surgery and diethylstilbestrol exposure in utero. A karyotype should be performed as Turner Syndrome is the most frequent genetic cause of POF. Some X abnormalities such as X deletion or X autosome translocation can be found. FMR1 pre-mutation (fragile X syndrome) should be searched for, even though no cases of mental retardation are known, in the family. Other genetic abnormalities can be suggested by associated symptoms (i.e.: FOXL2, SF1 mutations). Auto-immune aetiology can be suspected if other auto-immune features are present, however, there are no reliable auto-antibodies to confirm auto-immunity in POF. Treatment of POF is based on hormonal replacement therapy in order to avoid estrogen deficiency, suppress vasomotor symptoms and avoid bone loss as well as cardiovascular risk. Estrogens should be associated with progesterone or a progestin, at least up to the age of 51. Patients with POF should be informed that spontaneous pregnancies may occur (in 5% of cases). In case of desire of pregnancy, the patient should be oriented to a specialized unit for in vitro fertilization with oocyte donation. Psychological support is essential and should be part of the treatment. POF is associated with an increased risk of emotional distress and depression. No preventive treatment of POF is available so far. PMID:24157186

  5. [Ovarian tumor markers of presumed benign ovarian tumors].

    PubMed

    Lahlou, N; Brun, J-L

    2013-12-01

    Cancer Antigen 125 (CA125) and Human Epididymis Protein 4 (HE4) are the most studied ovarian tumor markers. Their diagnostic performance for identification of ovarian cancer are superior to CA19-9, CA72-4, and carcinoembryonic antigen, which are no more recommended for the diagnosis of presumed benign ovarian tumor. HE4 (>140 pmol/L) is superior to CA125 (>30 U/mL) in terms of specificity and positive likelihood ratio. CA125 and HE4 can be combined into an algorithm ROMA, or associated to clinical information (composite index), biological data (OVA1) or imaging (Risk for Malignancy Index (RMI), LR2). ROMA algorithm is an exponential equation combining plasmatic concentrations of HE4 and CA125. ROMA is more sensitive and less specific than HE4 in predicting epithelial ovarian cancer. ROMA is more accurate in post-menopausal women. The performance of ROMA is lower than the ultrasound model LR2 in differentiating malignant from benign ovarian tumors, whatever the hormonal status. The composite index combining CA125 with a symptoms index (pain, abdominal distension, bloating, difficulty eating) has a good sensitivity in a screening program, but because of a 12% false positive rate, ultrasound is required before management. The RMI algorithm is based on serum CA125, ultrasound findings (septation, solid zones, metastases, ascite, bilaterality) and menopausal status. RMI is less sensitive, but more specific than ROMA or OVA1 for the classification of ovarian masses. The addition of HE4 to RMI seems to be the most accurate. The subjective evaluation of ovarian cysts by sonography and color Doppler is better than ROMA and RMI algorithms, and not affected by the hormonal status.

  6. Ovarian carcinoma. A decade of progress.

    PubMed

    Piver, M S

    1984-12-01

    Significant and dramatic progress has been made in the diagnosis and treatment of women with ovarian carcinoma in the last 10 years, the results of which are now just being reflected in an increase in survival and cure rates. In early staged disease (Stage I and II) significant progress has been made concerning our understanding of the sites of subclinical metastasis when at surgery the tumor is clinically limited to the ovary or pelvis. A prospective study of 100 patients with Stages IA to IIB ovarian cancer who underwent restaging within 4 weeks of initial surgery will report this. Moreover, preliminary results of the first randomized therapeutic trials (melphalan versus observation; melphalan versus chromic phosphate [P-32]) in patients surgically staged and found to be Stage IA to IIB carcinoma will be discussed. For Stages IB to III, the 5-year survival rates comparing whole abdominal radiation by the moving strip technique to open field irradiation will be discussed. For advanced (Stage III and IV) ovarian carcinoma, the new techniques in debulking surgery will be illustrated. Finally, the significant progress in response rates, median duration of survival, disease-free survival, and 5-year survival rates made during the past 10 years will be presented. This will be done by comparing a unique group of 117 patients treated with melphalan alone, all of whom have been followed for 5 years or until death, to patients who received cisplatin combination chemotherapy--cyclophosphamide, hexamethylmelamine, Adriamycin (doxorubicin), and cisplatin (CHAD) or cisplatin, Adriamycin, and cyclophosphamide (PAC)--and have now been followed 3.4+ and 4+ years, respectively. What is clearly evident is that in the last decade there has been significant increase in response rates, median duration of survival, 3.4+-, 4+-, and 5-year survival rates and cure rates with the advent of debulking surgery and platinum-containing combination chemotherapy.

  7. Understanding Your Adequate Yearly Progress (AYP), 2011-2012

    ERIC Educational Resources Information Center

    Missouri Department of Elementary and Secondary Education, 2011

    2011-01-01

    The "No Child Left Behind Act (NCLB) of 2001" requires all schools, districts/local education agencies (LEAs) and states to show that students are making Adequate Yearly Progress (AYP). NCLB requires states to establish targets in the following ways: (1) Annual Proficiency Target; (2) Attendance/Graduation Rates; and (3) Participation Rates.…

  8. 15 CFR 970.404 - Adequate exploration plan.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 15 Commerce and Foreign Trade 3 2014-01-01 2014-01-01 false Adequate exploration plan. 970.404...) NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE GENERAL REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES Certification of...

  9. 15 CFR 970.404 - Adequate exploration plan.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 15 Commerce and Foreign Trade 3 2012-01-01 2012-01-01 false Adequate exploration plan. 970.404...) NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE GENERAL REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES Certification of...

  10. 15 CFR 970.404 - Adequate exploration plan.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 15 Commerce and Foreign Trade 3 2013-01-01 2013-01-01 false Adequate exploration plan. 970.404...) NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE GENERAL REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES Certification of...

  11. 15 CFR 970.404 - Adequate exploration plan.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 15 Commerce and Foreign Trade 3 2011-01-01 2011-01-01 false Adequate exploration plan. 970.404...) NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE GENERAL REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES Certification of...

  12. 15 CFR 970.404 - Adequate exploration plan.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Adequate exploration plan. 970.404...) NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE GENERAL REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES Certification of...

  13. Adequate Schools and Inadequate Education: An Anthropological Perspective.

    ERIC Educational Resources Information Center

    Wolcott, Harry F.

    To illustrate his claim that schools generally do a remarkably good job of schooling while the society makes inadequate use of other means to educate young people, the author presents a case history of a young American (identified pseudonymously as "Brad") whose schooling was adequate but whose education was not. Brad, jobless and homeless,…

  14. Comparability and Reliability Considerations of Adequate Yearly Progress

    ERIC Educational Resources Information Center

    Maier, Kimberly S.; Maiti, Tapabrata; Dass, Sarat C.; Lim, Chae Young

    2012-01-01

    The purpose of this study is to develop an estimate of Adequate Yearly Progress (AYP) that will allow for reliable and valid comparisons among student subgroups, schools, and districts. A shrinkage-type estimator of AYP using the Bayesian framework is described. Using simulated data, the performance of the Bayes estimator will be compared to…

  15. 13 CFR 107.200 - Adequate capital for Licensees.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 13 Business Credit and Assistance 1 2012-01-01 2012-01-01 false Adequate capital for Licensees. 107.200 Section 107.200 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION SMALL BUSINESS... operate actively in accordance with your Articles and within the context of your business plan,...

  16. Assessing Juvenile Sex Offenders to Determine Adequate Levels of Supervision.

    ERIC Educational Resources Information Center

    Gerdes, Karen E.; And Others

    1995-01-01

    This study analyzed the internal consistency of four inventories used by Utah probation officers to determine adequate and efficacious supervision levels and placement for juvenile sex offenders. Three factors accounted for 41.2 percent of variance (custodian's and juvenile's attitude toward intervention, offense characteristics, and historical…

  17. Do Beginning Teachers Receive Adequate Support from Their Headteachers?

    ERIC Educational Resources Information Center

    Menon, Maria Eliophotou

    2012-01-01

    The article examines the problems faced by beginning teachers in Cyprus and the extent to which headteachers are considered to provide adequate guidance and support to them. Data were collected through interviews with 25 school teachers in Cyprus, who had recently entered teaching (within 1-5 years) in public primary schools. According to the…

  18. Immunobiology of human mucin 1 in a preclinical ovarian tumor model

    PubMed Central

    Budiu, RA; Elishaev, E; Brozick, J; Lee, M; Edwards, RP; Kalinski, P; Vlad, AM

    2014-01-01

    Epithelial ovarian cancer is an aggressive malignancy, with a low 5-year median survival. Continued improvement on the development of more effective therapies depends in part on the availability of adequate preclinical models for in vivo testing of treatment efficacy. Mucin 1 (MUC1) glycoprotein is a tumor-associated antigen overexpressed in ovarian cancer cells, making it a potential target for immune therapy. To create a preclinical mouse model for MUC1-positive ovarian tumors, we generated triple transgenic (Tg) mice that heterozygously express human MUC1+/− as a transgene, and carry the conditional K-rasG12D oncoallele (loxP-Stop-loxP-K-rasG12D/+) and the floxed Pten gene (Pten/loxP/loxP). Injection of Cre recombinase-encoding adenovirus (AdCre) in the ovarian bursa of triple (MUC1KrasPten) Tg mice triggers ovarian tumors that, in analogy to human ovarian cancer, express strongly elevated MUC1 levels. The tumors metastasize loco-regionally and are accompanied by high serum MUC1, closely mimicking the human disease. Compared with the KrasPten mice with tumors, the MUC1KrasPten mice show increased loco-regional metastasis and augmented accumulation of CD4+Foxp3+ immune-suppressive regulatory T cells. Vaccination of MUC1KrasPten mice with type 1 polarized dendritic cells (DC1) loaded with a MUC1 peptide (DC1–MUC1) can circumvent tumor-mediated immune suppression in the host, activate multiple immune effector genes and effectively prolong survival. Our studies report the first human MUC1-expressing, orthotopic ovarian tumor model, reveal novel MUC1 functions in ovarian cancer biology and demonstrate its suitability as a target for immune-based therapies. PMID:22964632

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

    ClinicalTrials.gov

    2016-08-19

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

  20. Exercise May Help Thwart Ovarian Cancer

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_159486.html Exercise May Help Thwart Ovarian Cancer Chronic inactivity linked ... TUESDAY, June 21, 2016 (HealthDay News) -- Lack of exercise is associated with an increased risk of ovarian ...

  1. FDA Warns Ovarian Cancer Tests Not Reliable

    MedlinePlus

    ... medlineplus.gov/news/fullstory_160880.html FDA Warns Ovarian Cancer Tests Not Reliable May delay preventive therapies for ... Sept. 9, 2016 (HealthDay News) -- Screening tests for ovarian cancer are not reliable and should not be used, ...

  2. Ovarian cancer: etiology, risk factors, and epidemiology.

    PubMed

    Hunn, Jessica; Rodriguez, Gustavo C

    2012-03-01

    Little is known regarding the early aspects of ovarian carcinogenesis. As a consequence, the identification of women at risk for the disease is based primarily on clinical grounds, with family history being the most important risk factor. In this review, we will discuss the various hypotheses regarding ovarian etiology and pathogenesis. In addition, we will discuss the epidemiology of ovarian cancer, including hereditary, reproductive, hormonal, inflammatory, dietary, surgical, and geographic factors that influence ovarian cancer risk.

  3. Biomarker-based ovarian carcinoma typing: a histological investigation in the Ovarian Tumor Tissue Analysis consortium

    PubMed Central

    Köbel, Martin; Kalloger, Steve E.; Lee, Sandra; Duggan, Máire A.; Kelemen, Linda E.; Prentice, Leah; Kalli, Kimberly R.; Fridley, Brooke L.; Visscher, Daniel W.; Keeney, Gary L.; Vierkant, Robert A.; Cunningham, Julie M.; Chow, Christine; Ness, Roberta B.; Moysich, Kirsten; Edwards, Robert; Modugno, Francesmary; Bunker, Clareann; Wozniak, Eva L.; Benjamin, Elizabeth; Gayther, Simon A.; Gentry-Maharaj, Aleksandra; Menon, Usha; Gilks, C. Blake; Huntsman, David G.; Ramus, Susan J.; Goode, Ellen L.

    2014-01-01

    Background Ovarian carcinoma is composed of five major histological types which associate with outcome and predict therapeutic response. Our aim was to evaluate histological type assessments across centres participating in the Ovarian Tumor Tissue Analysis (OTTA) consortium using an immunohistochemical (IHC) prediction model. Methods Tissue microarrays (TMAs) and clinical data were available for 524 pathologically confirmed ovarian carcinomas. Centralized IHC was performed for ARID1A, CDKN2A, DKK1, HNF1B, MDM2, PGR, TP53, TFF3, VIM, and WT1, and three histological type assessments were compared: the original pathologic type, an IHC-based calculated type (termed TB_COSPv2), and a WT1-assisted TMA core review. Results The concordance between TB_COSPv2 type and original type was 73%. Applying WT1-assisted core review, the remaining 27% discordant cases subdivided into unclassifiable (6%), TB_COSPv2 error (6%), and original type error (15%). The largest discordant subgroup was classified as endometrioid carcinoma (EC) by original type and as high-grade serous carcinoma (HGSC) by TB_COSPv2. When TB_COSPv2 classification was used, the difference in overall survival of EC compared to HGSC became significant (RR 0.60, 95% CI 0.37–0.93, p=0.021), consistent with previous reports. In addition, 71 cases with unclear original type could be histologically classified by TB_COSPv2. Conclusions Research cohorts, particularly those across different centres within consortia, show significant variability in original histological type diagnosis. Our IHC-based reclassification produced more homogeneous types with respect to outcome than original type. Impact Biomarker-based classification of ovarian carcinomas is feasible, improves comparability of results across research studies, and can reclassify cases which lack reliable original pathology. PMID:23880734

  4. An Update on Ovarian Aging and Ovarian Reserve Tests

    PubMed Central

    Amanvermez, Ramazan; Tosun, Migraci

    2016-01-01

    Ovaries are the female organs that age more quickly than other tissues such as the uterus, the pituitary gland or pancreas. Different from males, an interesting question is why and how the females lose fertility so rapidly. During the aging process, both the number and quality of the oocytes in the ovaries decrease and reach to a point beyond that no more viable offspring may be produced and the associated cyclic endocrinological activities cease, entering the menopause in females at an average age of 50 years. Females who delayed childbearing with or without their willing until their 30 years or 40 years constitute the largest portion of the total infertility population. Ovarian reserve tests (ORTs) provide an indirect estimate of a female’s diminishing ovarian reserve or remaining follicular pool. This article briefly reviews recent progresses in relation to ovarian aging and ORTs. PMID:26985328

  5. 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

  6. Pediatric ovarian torsion: a pictorial review.

    PubMed

    Ngo, Anh-Vu; Otjen, Jeffrey P; Parisi, Marguerite T; Ferguson, Mark R; Otto, Randolph K; Stanescu, A Luana

    2015-11-01

    Imaging is crucial in expediting the diagnosis and guiding definitive therapy in children with ovarian torsion. This article reviews the multimodality spectrum of imaging findings in pediatric ovarian torsion, focusing primarily on US appearances. We describe predisposing conditions that can lead to torsion, the pathological basis of the radiologic findings in ovarian torsion, and the common diagnostic pitfalls.

  7. A T cell-independent antitumor response in mice with bone marrow cells retrovirally transduced with an antibody/Fc-gamma chain chimeric receptor gene recognizing a human ovarian cancer antigen.

    PubMed

    Wang, G; Chopra, R K; Royal, R E; Yang, J C; Rosenberg, S A; Hwu, P

    1998-02-01

    In order to treat common cancers with immunotherapy, chimeric receptors have been developed that combine the tumor specificity of antibodies with T-cell effector functions. Previously, we demonstrated that T cells transduced with a chimeric receptor gene against human ovarian cancer were able to recognize ovarian cancer cells in vitro and in vivo. We now report that recipients of bone marrow cells transduced with these genes exhibited significant antitumor activity in vivo. Moreover, in vivo depletion of T cells in reconstituted mice did not affect antitumor activity, suggesting that other immune cells expressing the chimeric receptor gene may play an important role in tumor rejection.

  8. The epidemiology of ovarian cancer.

    PubMed

    Greene, M H; Clark, J W; Blayney, D W

    1984-09-01

    Although no unequivocally effective ovarian cancer prevention strategies have emerged, epidemiologic studies have identified high-risk populations. The striking international variation (apparently a fivefold difference) can probably be explained on the basis of differential parity, differing classification measures, and differences in the underlying population age distribution. United States age-adjusted mortality has increased slightly in the past 30 years, and the cancer remains predominantly a disease of older adult white women of northern European extraction. The increases in age-specific mortality and age-adjusted mortality over time may be related to a decrease in average family size. Pregnancy, especially pregnancy before age 25 years, and use of oral contraceptives are protective; the risk of ovarian cancer increases with increasing years of ovulation. A positive family history is also associated with a substantial increase in ovarian cancer risk. Survivors of ovarian cancer are more susceptible to cancers of the breast, endometrium, and colon than are similarly-aged normal women, most probably because all four cancers share some common risk factor(s). Various alkylating agents are clearly leukemogenic in survivors of ovarian cancer, an observation that suggests caution in the use of adjuvant chemotherapy in women at relatively low risk of relapse.

  9. Paraneoplastic syndromes revealing ovarian teratoma in young and menopausal women: report of two cases

    PubMed Central

    Boujoual, Majdouline; Hakimi, Ihsan; Kassidi, Farid; Akhoudad, Youssef; Sahel, Nawal; Rkiouak, Adil; Allaoui, Mohamed; Chahdi, Hafsa; Oukabli, Mohamed; Kouach, Jaouad; Moussaoui, Driss Rahali; Dehayni, Mohamed

    2016-01-01

    Paraneoplastic syndromes are a heterogeneous group of clinical and biological manifestations caused by underling neoplasms. They can reveal ovarian teratoma which express neuroendocrine proteins, or contain mature or immature neural tissue inducing an autoimmune response. The etiological investigation is then crucial to early identification of the tumor in order to optimize the prognosis and to limit neurological sequelae. In case of ovarian teratoma, management is essentially based on surgical resection sometimes associated with immunotherapie. We report two new cases of ovarian teratoma revealed by paraneoplastic syndromes in young and menopausal woman. PMID:27795759

  10. 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

  11. Regulation of ovarian hyperluteinization.

    PubMed

    Ivanisevic-Milovanovic, O K; Demajo, M A; Karakasevic, A M; Pantic, V R

    1998-01-01

    Adult female rats with neonatally damaged posterior hypothalamus, made by a transversal cut, were investigated. Plasma levels of prolactin (PRL), gonadotropic hormones (GTH) and female gonadal steroids (GS) were determined by radioimmunoassay. The animals were sacrificed, at the ages of 4 and 6 months and their hypothalamus, pituitary gland, ovary and uterus were examined using light microscopy. The results can be summarized as follows: body mass of animals, with damaged posterior hypothalamus, was significantly reduced. Masses of luteinized ovaries were increased and uterine tissues decreased. Serum levels of PRL were significantly increased and luteinizing hormone (LH) decreased. Ultrastructural changes in the corpora lutea (CL), previously described, showed clear signs of their reduced capacities to produce GS, both estradiol (Oe) and progesterone (Pg) per total ovarian mass. However, prostaglandin 2 alfa (PGF2alpha) known as a luteolytic factor, was also diminished in the evidently retarded endometrium. As a result of decreased plasma values of LH, Pg and PGF2 alpha, luteolysis of CL in hyperluteinized ovaries did not occur, and their new generations were accumulated during subsequent cycles. The character of interruption and recovery of aminergic and peptidergic neurons, involved in regulation of hypothalamic-pituitary gonadal axis and feed-back effects of steroid hormones, require further studies.

  12. Impact of food restriction on ovarian development, RFamide-related peptide-3 and the hypothalamic-pituitary-ovarian axis in pre-pubertal ewes.

    PubMed

    Li, H; Song, H; Huang, M; Nie, H; Wang, Z; Wang, F

    2014-10-01

    RFamide-related peptide-3 (RFRP-3), the mammalian ortholog of gonadotropin-inhibiting hormone, has been implicated as a mediator between reproduction and energy balance. This study aimed to investigate the physiological effects of RFRP-3 on the process of ovarian development in food-restricted pre-pubertal ewes. The results showed that food restriction significantly inhibited the ovarian development and follicular growth. The data of qPCR in the hypothalamic-pituitary-ovarian (HPO) axis showed that food restriction not only upregulated RFRP-3 mRNA expression but also downregulated the mRNA expression of gonadotropin-releasing-hormone receptor, follicle-stimulating hormone receptor and luteinizing hormone receptor (LHR). Immunohistochemistry of RFRP-3 in the ovaries suggested that RFRP-3 may regulate the follicular development. These results suggested that the changes of RFRP-3 in response to food restriction might influence the HPO axis and inhibit ovarian development.

  13. Mathematical models of breast and ovarian cancers.

    PubMed

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

    2016-07-01

    Women constitute the majority of the aging United States (US) population, and this has substantial implications on cancer population patterns and management practices. Breast cancer is the most common women's malignancy, while ovarian cancer is the most fatal gynecological malignancy in the US. In this review, we focus on these subsets of women's cancers, seen more commonly in postmenopausal and elderly women. In order to systematically investigate the complexity of cancer progression and response to treatment in breast and ovarian malignancies, we assert that integrated mathematical modeling frameworks viewed from a systems biology perspective are needed. Such integrated frameworks could offer innovative contributions to the clinical women's cancers community, as answers to clinical questions cannot always be reached with contemporary clinical and experimental tools. Here, we recapitulate clinically known data regarding the progression and treatment of the breast and ovarian cancers. We compare and contrast the two malignancies whenever possible in order to emphasize areas where substantial contributions could be made by clinically inspired and validated mathematical modeling. We show how current paradigms in the mathematical oncology community focusing on the two malignancies do not make comprehensive use of, nor substantially reflect existing clinical data, and we highlight the modeling areas in most critical need of clinical data integration. We emphasize that the primary goal of any mathematical study of women's cancers should be to address clinically relevant questions. WIREs Syst Biol Med 2016, 8:337-362. doi: 10.1002/wsbm.1343 For further resources related to this article, please visit the WIREs website. PMID:27259061

  14. 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

  15. 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

  16. 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

  17. Knockdown of HVEM, a Lymphocyte Regulator Gene, in Ovarian Cancer Cells Increases Sensitivity to Activated T Cells.

    PubMed

    Zhang, Ting; Ye, Lei; Han, Lingfei; He, Qizhi; Zhu, Jianlong

    2016-01-01

    Ovarian cancer is highly malignant with a gradually increasing incidence and a high mortality rate. Immunosuppression is induced in ovarian cancer, although the mechanism detail is not clear. It has been indicated that HVEM (herpesvirus entry mediator) B- and T-lymphocyte attenuator (BTLA) negatively regulates the immune responses of T lymphocytes. Here, HVEM mRNA was found to be elevated in ovarian cancer tissue samples and primary ovarian cancer cells in comparison with benign tissue samples. We then knocked down HVEM expression in an ovarian cancer cell line, OVCAR3, by lentivirus-based small hairpin RNA (shRNA). Cell Counting Kit-8 (CCK-8) assay and flow cytometry analysis showed that HVEM-shRNA had no effect on the proliferation, early apoptosis, or cell cycle distribution of OVCAR3. We then isolated activated T cells and performed coculture experiments in Transwell. Remarkably, HVEM-silenced ovarian cancer cells (primary ovarian cancer cells and OVCAR3) increased the number of T cells and the secretion of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), while activated T cells promoted the apoptosis of HVEM-silenced ovarian cancer cells. The current study partially explains the immune escape mechanism of ovarian cancer cells and provides a possible target for immunotherapy. PMID:27458100

  18. 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

  19. Epithelial Ovarian Cancer Experimental Models

    PubMed Central

    Lengyel, E; Burdette, JE; Kenny, HA; Matei, D; Pilrose, J; Haluska, P.; Nephew, KP; Hales, DB; Stack, MS

    2014-01-01

    Epithelial ovarian cancer (OvCa) is associated with high mortality and, as the majority (>75%) of women with OvCa have metastatic disease at the time of diagnosis, rates of survival have not changed appreciably over 30 years. A mechanistic understanding of OvCa initiation and progression is hindered by the complexity of genetic and/or environmental initiating events and lack of clarity regarding the cell(s) or tissue(s) of origin. Metastasis of OvCa involves direct extension or exfoliation of cells and cellular aggregates into the peritoneal cavity, survival of matrix-detached cells in a complex ascites fluid phase, and subsequent adhesion to the mesothelium lining covering abdominal organs to establish secondary lesions containing host stromal and inflammatory components. Development of experimental models to recapitulate this unique mechanism of metastasis presents a remarkable scientific challenge and many approaches used to study other solid tumors (lung, colon, and breast, for example) are not transferable to OvCa research given the distinct metastasis pattern and unique tumor microenvironment. This review will discuss recent progress in the development and refinement of experimental models to study OvCa. Novel cellular, three-dimensional organotypic, and ex vivo models are considered and the current in vivo models summarized. The review critically evaluates currently available genetic mouse models of OvCa, the emergence of xenopatients, and the utility of the hen model to study OvCa prevention, tumorigenesis, metastasis, and chemoresistance. As these new approaches more accurately recapitulate the complex tumor microenvironment, it is predicted that new opportunities for enhanced understanding of disease progression, metastasis and therapeutic response will emerge. PMID:23934194

  20. 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.

  1. Etiology, biology, and epidemiology of ovarian cancer.

    PubMed

    Baker, T R; Piver, M S

    1994-01-01

    Epithelial ovarian cancer kills more women per year than all other gynecologic cancers combined. Pregnancy, oral contraceptive use, and tubal ligation decrease the risk of the disease, whereas risk is increased for women whose family history is consistent with one of the familial ovarian cancer syndromes. Several theories have been postulated concerning the etiology of ovarian cancer, including the incessant ovulation theory and that based on the model of hypergonadotropic hypogonadism. Chromosomal abnormalities and allele losses have been described in ovarian cancers. Involvement of oncogenes and tumor suppressor genes has been investigated as well. Genetic linkage studies are ongoing in families whose history is consistent with one of the familial ovarian cancer syndromes.

  2. Laparoscopic optical coherence tomography imaging of human ovarian cancer

    PubMed Central

    Hariri, Lida P.; Bonnema, Garret T.; Schmidt, Kathy; Winkler, Amy M.; Korde, Vrushali; Hatch, Kenneth D.; Davis, John R.; Brewer, Molly A.; Barton, Jennifer K.

    2011-01-01

    Objectives Ovarian cancer is the fourth leading cause of cancer-related death among women in the US largely due to late detection secondary to unreliable symptomology and screening tools without adequate resolution. Optical coherence tomography (OCT) is a recently emerging imaging modality with promise in ovarian cancer diagnostics, providing non-destructive subsurface imaging at imaging depths up to 2 mm with near-histological grade resolution (10–20 μm). In this study, we developed the first ever laparoscopic OCT (LOCT) device, evaluated the safety and feasibility of LOCT, and characterized the microstructural features of human ovaries in vivo. Methods A custom LOCT device was fabricated specifically for laparoscopic imaging of the ovaries in patients undergoing oophorectomy. OCT images were compared with histopathology to identify preliminary architectural imaging features of normal and pathologic ovarian tissue. Results Thirty ovaries in 17 primarily peri or post-menopausal women were successfully imaged with LOCT: 16 normal, 5 endometriosis, 3 serous cystadenoma, and 4 adenocarcinoma. Preliminary imaging features developed for each category reveal qualitative differences in the homogeneous character of normal post-menopausal ovary, the ability to image small subsurface inclusion cysts, and distinguishable features for endometriosis, cystadenoma, and adenocarcinoma. Conclusions We present the development and successful implementation of the first laparoscopic OCT probe. Comparison of OCT images and corresponding histopathology allowed for the description of preliminary microstructural features for normal ovary, endometriosis, and benign and malignant surface epithelial neoplasms. These results support the potential of OCT both as a diagnostic tool and imaging modality for further evaluation of ovarian cancer pathogenesis. PMID:19481241

  3. Perimenopausal ovarian carcinoma patient with subclavian node metastasis proven by immunohistochemistry.

    PubMed

    Jeong, Hee Jeong; Kim, Hyun Joo; Lee, Eun Hee; Lee, Hyoun Wook; Kim, Min Kyu

    2014-04-01

    Ovarian cancer is the seventh most common cancer in the world and the fifth most common cause of death from cancer; it is responsible for over half of all deaths related to gynecological cancers. The presence of lymphatic metastasis is an important prognostic factor in ovarian cancer. Nodal metastases to the pelvic and the para-aortic lymph nodes are common, particularly in an advanced of the disease (stages III-IV). The finding of distant nodal metastasis, especially subclavian lymph node metastasis, from ovarian carcinoma is very uncommon. 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) or FDG-PET/computed tomography (CT) provides an improved imaging for detecting metastatic lymph nodes in patients with ovarian cancer. Immunohistochemically, ovarian carcinoma cells are positive for estrogen receptor, progesterone receptor, cancer antigen 125, Wilms' tumor 1 protein, and p53; they are negative for thyroid transcription factor (TTF-1) and caudal-related homeobox 2 (CDX-2). This report describes a Korean woman diagnosed with ovarian cancer with subclavian lymph node metastasis revealed by FDG PET/CT and verified by an immunohistochemical staining. Differentiating between the primary ovarian lesion and the metastatic lesion will allow the initiation of an appropriate treatment and help predict the prognosis. PMID:25371892

  4. Massive Ovarian Oedema- A Case Report.

    PubMed

    Harke, Arun B; Sigamani, Karthik; Thukkaram, Chitra; Ramamurthy, Madhumittha; Sekar, Manjani

    2016-08-01

    Massive ovarian oedema is defined by WHO as formation of tumour like enlargement of one or both ovaries by oedema fluid. We report a case of a 18-year-old unmarried girl who presented with three months amenorrhoea and left sided lower abdominal pain with clinical and radiological diagnosis of cystic ovarian neoplasm. Patient underwent lapratomy with left salpingo-oophorectomy. A definitive diagnosis of Massive Ovarian Oedema (MOE) was offered on histopathological examination. The MOE should be differentiated from ovarian fibromatosis, ovarian fibroma, sclerosing stromal tumour and ovarian myxoma. The usual management of massive oedema of ovary is unilateral salpingo-oophorectomy, as the lesion is mistaken for primary ovarian neoplasm at laparotomy. Recognition of MOE is of great importance to prevent unnecessary oophorectomy in young patients and can be managed conservatively. We report this case of MOE for its rarity. PMID:27656451

  5. Defining ovarian reserve to better understand ovarian aging

    PubMed Central

    2011-01-01

    Though a widely utilized term and clinical concept, ovarian reserve (OR) has been only inadequately defined. Based on Medline and PubMed searches we here define OR in its various components, review genetic control of OR, with special emphasis on the FMR1 gene, and discuss whether diminished OR (DOR) is treatable. What is generally referred to as OR reflects only a small portion of total OR (TOR), a pool of growing (recruited) follicles (GFs) at different stages of maturation. Functional OR (FOR) depends on size of the follicle pool at menarche and the follicle recruitment rate. Both vary between individuals and, at least partially, are under genetic control. The FMR1 gene plays a role in defining FOR at all ages. Infertility treatments have in the past almost exclusively only centered on the last two weeks of folliculogenesis, the gonadotropin-sensitive phase. Expansions of treatments into earlier stages of maturation will offer opportunity to significantly improve ovarian stimulation protocols, especially in women with DOR. Dehydroepiandrosterone (DHEA) may represent a first such intervention. Data generated in DHEA-supplemented women, indeed, suggest a new ovarian aging concept, based on aging of ovarian environments and not, as currently is believed, aging oocytes. PMID:21299886

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

    PubMed

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

    2015-12-01

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

  7. 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.

  8. [Abdominal cure procedures. Adequate use of Nobecutan Spray].

    PubMed

    López Soto, Rosa María

    2009-12-01

    Open abdominal wounds, complicated by infection and/or risk of eventration tend to become chronic and usually require frequent prolonged cure. Habitual changing of bandages develop into one of the clearest risk factors leading to the deterioration of perilesional cutaneous integrity. This brings with it new complications which draw out the evolution of the process, provoking an important deterioration in quality of life for the person who suffers this and a considerable increase in health costs. What is needed is a product and a procedure which control the risk of irritation, which protect the skin, which favor a patient's comfort and which shorten treatment requirements while lowering health care expenses. This report invites medical personnel to think seriously about the scientific rationale, and treatment practice, as to why and how to apply Nobecutan adequately, this reports concludes stating the benefits in the adequate use of this product. The objective of this report is to guarantee the adequate use of this product in treatment of complicated abdominal wounds. This product responds to the needs which are present in these clinical cases favoring skin care apt isolation and protection, while at the same time, facilitating the placement and stability of dressings and bandages used to cure wounds. In order for this to happen, the correct use of this product is essential; medical personnel must pay attention to precautions and recommendations for proper application. The author's experiences in habitual handling of this product during various years, included in the procedures for standardized cures for these wounds, corroborates its usefulness; the author considers use of this product to be highly effective while being simple to apply; furthermore, one succeeds in providing quality care and optimizes resources employed.

  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. 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

  11. An immunological insight into premature ovarian failure (POF).

    PubMed

    Dragojević-Dikić, Svetlana; Marisavljević, Dragomir; Mitrović, Ana; Dikić, Srdjan; Jovanović, Tomislav; Janković-Raznatović, Svetlana

    2010-09-01

    Premature ovarian failure (POF), a serious life-changing condition that affects young women, remains an enigma and the researchers' challenge. The term POF generally describes a syndrome of gonadal failure before the age of 40, characterized by amenorrhea, sex steroid deficiency and elevated levels of gonadotropins. Infertility and psychological stress are common consequences of this entity the prevalence of which is 0.9-3%. The known cause of this condition includes: genetic aberrations, autoimmune ovarian damage, iatrogenic and environmental factors, although in majority of cases the underlying cause is not identified. For many women in whom the cause of ovarian failure is unknown, autoimmunity may be the pathogenic mechanism. There is currently evidence that some cases of POF are due to faulty recognition of self in the ovary by the immune system, possibly provoked by genetic or environmental factors initiating such immune response. Numerous evidence, including association with multiple autoimmune endocrine disorders, clinical reversibility, transitory estrogen deficiency, histological and immunological features and the demonstration of circulating ovarian antibodies in serum samples from women with POF, have suggested its immunological origin. We discuss the possible role of such an autoimmune process as a cause or consequence of POF including treatment strategies in POF patients.

  12. Quantifying dose to the reconstructed breast: Can we adequately treat?

    SciTech Connect

    Chung, Eugene; Marsh, Robin B.; Griffith, Kent A.; Moran, Jean M.; Pierce, Lori J.

    2013-04-01

    To evaluate how immediate reconstruction (IR) impacts postmastectomy radiotherapy (PMRT) dose distributions to the reconstructed breast (RB), internal mammary nodes (IMN), heart, and lungs using quantifiable dosimetric end points. 3D conformal plans were developed for 20 IR patients, 10 autologous reconstruction (AR), and 10 expander-implant (EI) reconstruction. For each reconstruction type, 5 right- and 5 left-sided reconstructions were selected. Two plans were created for each patient, 1 with RB coverage alone and 1 with RB + IMN coverage. Left-sided EI plans without IMN coverage had higher heart Dmean than left-sided AR plans (2.97 and 0.84 Gy, p = 0.03). Otherwise, results did not vary by reconstruction type and all remaining metrics were evaluated using a combined AR and EI dataset. RB coverage was adequate regardless of laterality or IMN coverage (Dmean 50.61 Gy, D95 45.76 Gy). When included, IMN Dmean and D95 were 49.57 and 40.96 Gy, respectively. Mean heart doses increased with left-sided treatment plans and IMN inclusion. Right-sided treatment plans and IMN inclusion increased mean lung V{sub 20}. Using standard field arrangements and 3D planning, we observed excellent coverage of the RB and IMN, regardless of laterality or reconstruction type. Our results demonstrate that adequate doses can be delivered to the RB with or without IMN coverage.

  13. 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.

  14. Differential effects of rapalogues, dual kinase inhibitors on human ovarian carcinoma cells in vitro

    PubMed Central

    ROGERS-BROADWAY, KARLY-RAI; CHUDASAMA, DIMPLE; PADOS, GEORGE; TSOLAKIDIS, DIMITRIS; GOUMENOU, ANASTASIA; HALL, MARCIA; KARTERIS, EMMANOUIL

    2016-01-01

    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. PMID:27211906

  15. [Presumed ovarian benign tumors and fertility].

    PubMed

    Aubard, Y; Poirot, C

    2013-12-01

    We reviewed the studies about fertility-sparing in young patient presenting a benign ovarian tumor. It appears that more than the histologic nature of the ovarian cysts, it is the surgical treatment of the cyst which may decrease fertility. Some good practice of surgical procedures must be kept in mind when one manages a benign ovarian tumor in a young patient wishing to preserve her fertility: surgery should be avoided as much as possible; kystectomy is better than oophorectomy; no radical surgery should be done without pathological certitudes; electrocoagulation must be avoided on the cyst walls. In some situations, fertility is specially endangered: bilateral ovarian cysts, recurrence or strong probability of recurrence (endometriomas), poor ovarian reserve (previous chemo- or radiotherapy, age>35, premature ovarian failure). In these situations, a pre-operative assessment of the ovarian reserve could be useful. Beside the surgical 'good procedures', gamete cryopreservation procedures could be used. Cryopreservation of mature oocytes (after ovarian hyperstimulation) or in vitro mature oocytes (after antral follicle retrieval) can be proposed. Ovarian tissue cryopreservation is another option. Oocyte (or embryos) cryopreservation can be proposed before or after the surgery. The global management of benign ovarian tumors in young patients should be decided between surgeons and specialists in reproductive biology.

  16. 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

  17. Hormone Receptors in Serous Ovarian Carcinoma: Prognosis, Pathogenesis, and Treatment Considerations

    PubMed Central

    Voutsadakis, Ioannis A.

    2016-01-01

    A few breakthroughs have been accomplished for the treatment of ovarian cancer, the most deadly gynecologic carcinoma, in the current era of targeted oncologic treatment. The estrogen receptor was the first target of such treatments with the introduction of tamoxifen four decades ago in breast cancer therapeutics. Attempts to duplicate the success of hormonal therapies in ovarian cancer met with mixed results, which may be due to an inferior degree of hormone dependency in this cancer. Alternatively, this may be due to the failure to clearly identify the subsets of ovarian cancer with hormone sensitivity. This article reviews the expression of hormone receptors by ovarian cancer cells, the prognostic value of these expressions, and their predictive capacity for response to hormonal agents. The possible ways ahead are briefly discussed. PMID:27053923

  18. Choices for achieving adequate dietary calcium with a vegetarian diet.

    PubMed

    Weaver, C M; Proulx, W R; Heaney, R

    1999-09-01

    To achieve adequate dietary calcium intake, several choices are available that accommodate a variety of lifestyles and tastes. Liberal consumption of dairy products in the diet is the approach of most Americans. Some plants provide absorbable calcium, but the quantity of vegetables required to reach sufficient calcium intake make an exclusively plant-based diet impractical for most individuals unless fortified foods or supplements are included. Also, dietary constituents that decrease calcium retention, such as salt, protein, and caffeine, can be high in the vegetarian diet. Although it is possible to obtain calcium balance from a plant-based diet in a Western lifestyle, it may be more convenient to achieve calcium balance by increasing calcium consumption than by limiting other dietary factors.

  19. Genetic Modification of Preimplantation Embryos: Toward Adequate Human Research Policies

    PubMed Central

    Dresser, Rebecca

    2004-01-01

    Citing advances in transgenic animal research and setbacks in human trials of somatic cell genetic interventions, some scientists and others want to begin planning for research involving the genetic modification of human embryos. Because this form of genetic modification could affect later-born children and their offspring, the protection of human subjects should be a priority in decisions about whether to proceed with such research. Yet because of gaps in existing federal policies, embryo modification proposals might not receive adequate scientific and ethical scrutiny. This article describes current policy shortcomings and recommends policy actions designed to ensure that the investigational genetic modification of embryos meets accepted standards for research on human subjects. PMID:15016248

  20. Ovarian cancer and the immune system - The role of targeted therapies.

    PubMed

    Turner, Taylor B; Buchsbaum, Donald J; Straughn, J Michael; Randall, Troy D; Arend, Rebecca C

    2016-08-01

    The majority of patients with epithelial ovarian cancer are diagnosed with advanced disease. While many of these patients will respond initially to chemotherapy, the majority will relapse and die of their disease. Targeted therapies that block or activate specific intracellular signaling pathways have been disappointing. In the past 15years, the role of the immune system in ovarian cancer has been investigated. Patients with a more robust immune response, as documented by the presence of lymphocytes infiltrating within their tumor, have increased survival and better response to chemotherapy. In addition, a strong immunosuppressive environment often accompanies ovarian cancer. Recent research has identified potential therapies that leverage the immune system to identify and destroy tumor cells that previously evaded immunosurveillance mechanisms. In this review, we discuss the role of the immune system in ovarian cancer and focus on specific pathways and molecules that show a potential for targeted therapy. We also review the ongoing clinical trials using targeted immunotherapy in ovarian cancer. The role of targeted immunotherapy in patients with ovarian cancer represents a field of growing research and clinical importance. PMID:27174875

  1. Metabolomic Characterization of Ovarian Epithelial Carcinomas by HRMAS-NMR Spectroscopy

    PubMed Central

    Ben Sellem, D.; Elbayed, K.; Neuville, A.; Moussallieh, F.-M.; Lang-Averous, G.; Piotto, M.; Bellocq, J.-P.; Namer, I. J.

    2011-01-01

    Objectives. The objectives of the present study are to determine if a metabolomic study by HRMAS-NMR can (i) discriminate between different histological types of epithelial ovarian carcinomas and healthy ovarian tissue, (ii) generate statistical models capable of classifying borderline tumors and (iii) establish a potential relationship with patient's survival or response to chemotherapy. Methods. 36 human epithelial ovarian tumor biopsies and 3 healthy ovarian tissues were studied using 1H HRMAS NMR spectroscopy and multivariate statistical analysis. Results. The results presented in this study demonstrate that the three histological types of epithelial ovarian carcinomas present an effective metabolic pattern difference. Furthermore, a metabolic signature specific of serous (N-acetyl-aspartate) and mucinous (N-acetyl-lysine) carcinomas was found. The statistical models generated in this study are able to predict borderline tumors characterized by an intermediate metabolic pattern similar to the normal ovarian tissue. Finally and importantly, the statistical model of serous carcinomas provided good predictions of both patient's survival rates and the patient's response to chemotherapy. Conclusions. Despite the small number of samples used in this study, the results indicate that metabolomic analysis of intact tissues by HRMAS-NMR is a promising technique which might be applicable to the therapeutic management of patients. PMID:21577256

  2. Gene expression in human ovarian tissue after xenografting.

    PubMed

    Van Langendonckt, A; Romeu, L; Ambroise, J; Amorim, C; Bearzatto, B; Gala, J L; Donnez, J; Dolmans, M M

    2014-06-01

    Cryobanking and transplantation of ovarian tissue is a promising approach to restore fertility in cancer patients. However, ischemic stress following avascular ovarian cortex grafting is known to induce stromal tissue fibrosis and alterations in follicular development. The aim of the study was to analyze the impact of freeze-thawing and grafting procedures on gene expression in human ovarian tissue. Frozen-thawed ovarian tissue from 14 patients was xenografted for 7 days to nude mice and one ungrafted fragment was used as a control. Immediately after recovery, grafts were processed for RNA extraction and histological analysis. Their expression profile was screened by whole-genome oligonucleotide array (n = 4) and validated by reverse-transcriptase polymerase chain analysis (n = 10). After data filtering, the Limma package was used to build a linear regression model for each gene and to compute its fold change between tissues on Days 0 and 7. After adjusting the P-value by the Sidak method, 84 of the transcripts were significantly altered after 7 days of grafting, including matrix metalloproteinase-9 and -14 and angiogenic factors such as placental growth factor and C-X-C chemokine receptor type 4 (CXCR4). Major biological processes were related to tissue remodeling, including secretory processes, cellular adhesion and response to chemical and hormonal stimuli. Angiopoietin signaling, the interleukin-8 pathway and peroxisome proliferator-activated receptor activation were shown to be differentially regulated. On Day 7, overexpression was confirmed by PCR for interleukin-8, transforming growth factor-beta 1, matrix metalloproteinase-14 and CXCR4, compared with ungrafted controls. In conclusion, new as well as known genes involved in tissue restructuring and angiogenesis were identified and found to play a key role during the first days after human ovarian tissue transplantation. This will facilitate the development of strategies to optimize grafting techniques. PMID

  3. 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

  4. 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.

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

    PubMed

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

    2016-04-01

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

  6. Longterm management of Polycystic Ovarian Syndrome (PCOS).

    PubMed

    Bates, Gordon W; Legro, Richard S

    2013-07-01

    Polycystic Ovarian Syndrome (PCOS) has been associated with numerous reproductive and metabolic abnormalities. Despite tremendous advances in the management of reproductive dysfunction, insight into the metabolic implications of PCOS is limited by the lack of uniform diagnostic criteria, the heterogeneity of the condition and the presence of confounders including obesity. Obesity clearly has a role in long term health and may best predict both reproductive and metabolic dysfunction as well as negatively affect the response to treatment in women with PCOS. Diabetes, cardiovascular disease and cancer are also at the forefront of any risk assessment or comprehensive treatment strategy for these women. Lifestyle modifications including dietary changes, increased exercise and weight loss are appropriate first line interventions for many women with PCOS. Pharmaceuticals including metformin, lipid lowering agents and oral contraceptives should be tailored to the individual's risk profile and treatment goals.

  7. Longterm management of Polycystic Ovarian Syndrome (PCOS).

    PubMed

    Bates, Gordon W; Legro, Richard S

    2013-07-01

    Polycystic Ovarian Syndrome (PCOS) has been associated with numerous reproductive and metabolic abnormalities. Despite tremendous advances in the management of reproductive dysfunction, insight into the metabolic implications of PCOS is limited by the lack of uniform diagnostic criteria, the heterogeneity of the condition and the presence of confounders including obesity. Obesity clearly has a role in long term health and may best predict both reproductive and metabolic dysfunction as well as negatively affect the response to treatment in women with PCOS. Diabetes, cardiovascular disease and cancer are also at the forefront of any risk assessment or comprehensive treatment strategy for these women. Lifestyle modifications including dietary changes, increased exercise and weight loss are appropriate first line interventions for many women with PCOS. Pharmaceuticals including metformin, lipid lowering agents and oral contraceptives should be tailored to the individual's risk profile and treatment goals. PMID:23261983

  8. Evaluation of the antitumor effects of c-Myc-Max heterodimerization inhibitor 100258-F4 in ovarian cancer cells.

    PubMed

    Wang, Jiandong; Ma, Xiaoli; Jones, Hannah M; Chan, Leo Li-Ying; Song, Fang; Zhang, Weiyuan; Bae-Jump, Victoria L; Zhou, Chunxiao

    2014-01-01

    Epithelial ovarian carcinoma is the most lethal gynecological cancer due to its silent onset and recurrence with resistance to chemotherapy. Overexpression of oncogene c-Myc is one of the most frequently encountered events present in ovarian carcinoma. Disrupting the function of c-Myc and its downstream target genes is a promising strategy for cancer therapy. Our objective was to evaluate the potential effects of small-molecule c-Myc inhibitor, 10058-F4, on ovarian carcinoma cells and the underlying mechanisms by which 10058-F4 exerts its actions. Using MTT assay, colony formation, flow cytometry and Annexin V FITC assays, we found that 10058-F4 significantly inhibited cell proliferation of both SKOV3 and Hey ovarian cancer cells in a dose dependent manner through induction of apoptosis and cell cycle G1 arrest. Treatment with 10058-F4 reduced cellular ATP production and ROS levels in SKOV3 and Hey cells. Consistently, primary cultures of ovarian cancer treated with 10058-F4 showed induction of caspase-3 activity and inhibition of cell proliferation in 15 of 18 cases. The response to 10058-F4 was independent the level of c-Myc protein over-expression in primary cultures of ovarian carcinoma. These novel findings suggest that the growth of ovarian cancer cells is dependent upon c-MYC activity and that targeting c-Myc-Max heterodimerization could be a potential therapeutic strategy for ovarian cancer.

  9. Curcumin induces apoptosis by inhibiting sarco/endoplasmic reticulum Ca2+ ATPase activity in ovarian cancer cells.

    PubMed

    Seo, Jeong-Ah; Kim, Boyun; Dhanasekaran, Danny N; Tsang, Benjamin K; Song, Yong Sang

    2016-02-01

    Aberrant increase in the expression levels of sarco/endoplasmic reticulum calcium ATPase (SERCA), which regulates Ca(2+) homeostasis, has been observed in ovarian cancers. In this study, we demonstrated that curcumin increases cytosolic Ca(2+) concentration through inhibition of SERCA activity, causing apoptosis in ovarian cancer cells but not in normal cells, including peripheral blood mononuclear cells (PBMCs) and ovarian surface epithelial cells (OSE). Curcumin induced apoptosis in ovarian cancer cells in a concentration- and time-dependent manner. Cytosolic Ca(2+) flux was evident after the curcumin treatment (15 µM). Treatment with Ca(2+) chelator reduced curcumin-induced apoptosis, confirming the possible involvement of increased cytosolic Ca(2+) concentration in this response. Basal mRNA and protein levels of SERCA2 were significantly higher in ovarian cancer cells than in OSE. SERCA activity was suppressed by curcumin, with no effect on protein expression. Forced expression of the SERCA2b gene in ovarian cancer cells prevented curcumin-induced cytosolic Ca(2+) elevation and subsequent apoptosis, supporting an important role of SERCA in curcumin-induced apoptosis of ovarian cancer cells. Taken together, inhibition of SERCA activity by curcumin disrupts the Ca(2+) homeostasis and thereby promotes apoptosis in ovarian cancer cells.

  10. Age related increase in mTOR activity contributes to the pathological changes in ovarian surface epithelium

    PubMed Central

    Bajwa, Preety; Nagendra, Prathima B.; Nielsen, Sarah; Sahoo, Subhransu S.; Bielanowicz, Amanda; Lombard, Janine M.; Wilkinson, Erby J.; Miller, Richard A.; Tanwar, Pradeep S.

    2016-01-01

    Ovarian cancer is a disease of older women. However, the molecular mechanisms of ovarian aging and their contribution to the pathogenesis of ovarian cancer are currently unclear. mTOR signalling is a major regulator of aging as suppression of this pathway extends lifespan in model organisms. Overactive mTOR signalling is present in up to 80% of ovarian cancer samples and is associated with poor prognosis. This study examined the role of mTOR signalling in age-associated changes in ovarian surface epithelium (OSE). Histological examination of ovaries from both aged mice and women revealed OSE cell hyperplasia, papillary growth and inclusion cysts. These pathological lesions expressed bonafide markers of ovarian cancer precursor lesions, Pax8 and Stathmin 1, and were presented with elevated mTOR signalling. To understand whether overactive mTOR signalling is responsible for the development of these pathological changes, we analysed ovaries of the Pten trangenic mice and found significant reduction in OSE lesions compared to controls. Furthermore, pharmacological suppression of mTOR signalling significantly decreased OSE hyperplasia in aged mice. Treatment with mTOR inhibitors reduced human ovarian cancer cell viability, proliferation and colony forming ability. Collectively, we have established the role of mTOR signalling in age-related OSE pathologies and initiation of ovarian cancer. PMID:27036037

  11. Age related increase in mTOR activity contributes to the pathological changes in ovarian surface epithelium.

    PubMed

    Bajwa, Preety; Nagendra, Prathima B; Nielsen, Sarah; Sahoo, Subhransu S; Bielanowicz, Amanda; Lombard, Janine M; Wilkinson, J Erby; Miller, Richard A; Tanwar, Pradeep S

    2016-04-12

    Ovarian cancer is a disease of older women. However, the molecular mechanisms of ovarian aging and their contribution to the pathogenesis of ovarian cancer are currently unclear. mTOR signalling is a major regulator of aging as suppression of this pathway extends lifespan in model organisms. Overactive mTOR signalling is present in up to 80% of ovarian cancer samples and is associated with poor prognosis. This study examined the role of mTOR signalling in age-associated changes in ovarian surface epithelium (OSE). Histological examination of ovaries from both aged mice and women revealed OSE cell hyperplasia, papillary growth and inclusion cysts. These pathological lesions expressed bonafide markers of ovarian cancer precursor lesions, Pax8 and Stathmin 1, and were presented with elevated mTOR signalling. To understand whether overactive mTOR signalling is responsible for the development of these pathological changes, we analysed ovaries of the Pten trangenic mice and found significant reduction in OSE lesions compared to controls. Furthermore, pharmacological suppression of mTOR signalling significantly decreased OSE hyperplasia in aged mice. Treatment with mTOR inhibitors reduced human ovarian cancer cell viability, proliferation and colony forming ability. Collectively, we have established the role of mTOR signalling in age-related OSE pathologies and initiation of ovarian cancer.

  12. Curcumin induces apoptosis by inhibiting sarco/endoplasmic reticulum Ca2+ ATPase activity in ovarian cancer cells.

    PubMed

    Seo, Jeong-Ah; Kim, Boyun; Dhanasekaran, Danny N; Tsang, Benjamin K; Song, Yong Sang

    2016-02-01

    Aberrant increase in the expression levels of sarco/endoplasmic reticulum calcium ATPase (SERCA), which regulates Ca(2+) homeostasis, has been observed in ovarian cancers. In this study, we demonstrated that curcumin increases cytosolic Ca(2+) concentration through inhibition of SERCA activity, causing apoptosis in ovarian cancer cells but not in normal cells, including peripheral blood mononuclear cells (PBMCs) and ovarian surface epithelial cells (OSE). Curcumin induced apoptosis in ovarian cancer cells in a concentration- and time-dependent manner. Cytosolic Ca(2+) flux was evident after the curcumin treatment (15 µM). Treatment with Ca(2+) chelator reduced curcumin-induced apoptosis, confirming the possible involvement of increased cytosolic Ca(2+) concentration in this response. Basal mRNA and protein levels of SERCA2 were significantly higher in ovarian cancer cells than in OSE. SERCA activity was suppressed by curcumin, with no effect on protein expression. Forced expression of the SERCA2b gene in ovarian cancer cells prevented curcumin-induced cytosolic Ca(2+) elevation and subsequent apoptosis, supporting an important role of SERCA in curcumin-induced apoptosis of ovarian cancer cells. Taken together, inhibition of SERCA activity by curcumin disrupts the Ca(2+) homeostasis and thereby promotes apoptosis in ovarian cancer cells. PMID:26607901

  13. Early Detection Biomarkers for Ovarian Cancer

    PubMed Central

    Sarojini, Sreeja; Tamir, Ayala; Lim, Heejin; Li, Shihong; Zhang, Shifang; Goy, Andre; Pecora, Andrew; Suh, K. Stephen

    2012-01-01

    Despite the widespread use of conventional and contemporary methods to detect ovarian cancer development, ovarian cancer remains a common and commonly fatal gynecological malignancy. The identification and validation of early detection biomarkers highly specific to ovarian cancer, which would permit development of minimally invasive screening methods for detecting early onset of the disease, are urgently needed. Current practices for early detection of ovarian cancer include transvaginal ultrasonography, biomarker analysis, or a combination of both. In this paper we review recent research on novel and robust biomarkers for early detection of ovarian cancer and provide specific details on their contributions to tumorigenesis. Promising biomarkers for early detection of ovarian cancer include KLK6/7, GSTT1, PRSS8, FOLR1, ALDH1, and miRNAs. PMID:23319948

  14. GCIG Consensus Review: Uterine and Ovarian Leiomyosarcomas

    PubMed Central

    Hensley, Martee L.; Barrette, Brigitte A.; Baumann, Klaus; Gaffney, David; Hamilton, Anne L.; Kim, Jae-Weon; Maenpaa, Johanna U.; Pautier, Patricia; Siddiqui, Nadeem Ahmad; Westermann, Anneke M.; Ray-Coquard, Isabelle

    2016-01-01

    Objective The GCIG aimed to provide an overview of uterine and ovarian leiomyosarcoma management. Methods Published articles and author experience were used to draft management overview. The draft manuscript was circulated to international members of the GCIG for review and comment, and appropriate revisions were made. Results The approach to management of uterine and ovarian leiomyosarcoma management is reviewed. Conclusions Uterine and ovarian leiomyosarcomas are rare, aggressive cancers that require specialized expertise for optimal management. PMID:25341583

  15. Early Preinvasive Lesions in Ovarian Cancer

    PubMed Central

    Chene, Gautier; Lamblin, Gery; Le Bail-Carval, Karine; Chabert, Philippe; Bakrin, Naoual; Mellier, Georges

    2014-01-01

    Faced with the catastrophic prognosis for ovarian cancer due to the fact that it is most often diagnosed late at the peritoneal carcinomatosis stage, screening and early detection could probably reduce the mortality rate. A better understanding of the molecular characteristics of the different ovarian cancer subtypes and their specific molecular signatures is indispensable prior to development of new screening strategies. We discuss here the early natural history of ovarian cancer and its origins. PMID:24804229

  16. Multisystem manifestations of benign ovarian teratomas.

    PubMed

    Murdoch, William; Sadoski, Jill; Rosin, Frederick C

    2014-01-01

    A 26-year-old woman presented with acute onset of right-sided pelvic pain and had a medical history significant for migraine headaches and polycystic ovarian disease. Ultrasonography demonstrated bilateral ovarian tumors, and the patient underwent laparoscopic removal of bilateral cystic teratomas. A literature review focused on similar presentations of teratomas revealed isolated cases of migraines and polycystic ovarian disease associated with teratomas and an increased risk for ovarian torsion. Our patient experienced complete resolution of her acute abdominal pain, as well as her long-standing headaches and hormonal symptoms, after removal of the teratomas.

  17. Ovarian tissue characterization in ultrasound: a review.

    PubMed

    Acharya, U Rajendra; Molinari, Filippo; Sree, S Vinitha; Swapna, G; Saba, Luca; Guerriero, Stefano; Suri, Jasjit S

    2015-06-01

    Ovarian cancer is the most common cause of death among gynecological malignancies. We discuss different types of clinical and nonclinical features that are used to study and analyze the differences between benign and malignant ovarian tumors. Computer-aided diagnostic (CAD) systems of high accuracy are being developed as an initial test for ovarian tumor classification instead of biopsy, which is the current gold standard diagnostic test. We also discuss different aspects of developing a reliable CAD system for the automated classification of ovarian cancer into benign and malignant types. A brief description of the commonly used classifiers in ultrasound-based CAD systems is also given.

  18. Estrogen Biosynthesis and Action in Ovarian Cancer

    PubMed Central

    Mungenast, Felicitas; Thalhammer, Theresia

    2014-01-01

    Ovarian cancer is still the deadliest of all gynecologic malignancies in women worldwide. This is attributed to two main features of these tumors, namely, (i) a diagnosis at an advanced tumor stage, and, (ii) the rapid onset of resistance to standard chemotherapy after an initial successful therapy with platin- and taxol-derivatives. Therefore, novel targets for an early diagnosis and better treatment options for these tumors are urgently needed. Epidemiological data show that induction and biology of ovarian cancer is related to life-time estrogen exposure. Also experimental data reveal that ovarian cancer cells share a number of estrogen regulated pathways with other hormone-dependent cancers, e.g., breast and endometrial cancer. However, ovarian cancer is a heterogeneous disease and the subtypes are quite different with respect to mutations, origins, behaviors, markers, and prognosis and respond differently to standard chemotherapy. Therefore, a characterization of ovarian cancer subtypes may lead to better treatment options for the various subtypes and in particular for the most frequently observed high-grade serous ovarian carcinoma. For this intention, further studies on estrogen-related pathways and estrogen formation in ovarian cancer cells are warranted. The review gives an overview on ovarian cancer subtypes and explains the role of estrogen in ovarian cancer. Furthermore, enzymes active to synthesize and metabolize estrogens are described and strategies to target these pathways are discussed. PMID:25429284

  19. Ovarian Kaleidoscope database: ten years and beyond.

    PubMed

    Hsueh, Aaron J; Rauch, Rami

    2012-06-01

    Ovarian Kaleidoscope database (OKdb) is an online, searchable, public database containing text-based and DNA microarray data to facilitate research by ovarian researchers. Using key words and predetermined categories, users can search ovarian gene information based on gene function, cell type of expression, cellular localization, hormonal regulation, mutant phenotypes, chromosomal location, ligand-receptor relationship, and other criteria, either alone or in combination. For individual genes, users can access more than 10 extensive DNA microarray datasets to interrogate gene expression patterns in a development-specific and cell type-specific manner. All ligand and receptor genes expressed in the ovary are matched to facilitate investigation of paracrine/autocrine signaling. More than 3500 ovarian genes in the database are matched to 185 gene pathways in the Kyoto Encyclopedia of Genes and Genomes to allow for elucidation of gene interactions and relationships. In addition to >400 genes with infertility or subfertility phenotypes when mutated in mice or humans, the OKdb also lists ~50 and ~40 genes associated with polycystic ovarian syndrome and primary ovarian insufficiency, respectively. The expanding OKdb is updated weekly and allows submission of new genes by ovarian researchers to allow instant access to DNA microarray datasets for newly submitted genes. The present database is a virtual community for ovarian researchers and allows users to instantaneously provide their comments for individual gene pages based on an automated Web-discussion system. In the coming years, we will continue to add new features to serve the ovarian research community. PMID:22441797

  20. Ovarian tissue characterization in ultrasound: a review.

    PubMed

    Acharya, U Rajendra; Molinari, Filippo; Sree, S Vinitha; Swapna, G; Saba, Luca; Guerriero, Stefano; Suri, Jasjit S

    2015-06-01

    Ovarian cancer is the most common cause of death among gynecological malignancies. We discuss different types of clinical and nonclinical features that are used to study and analyze the differences between benign and malignant ovarian tumors. Computer-aided diagnostic (CAD) systems of high accuracy are being developed as an initial test for ovarian tumor classification instead of biopsy, which is the current gold standard diagnostic test. We also discuss different aspects of developing a reliable CAD system for the automated classification of ovarian cancer into benign and malignant types. A brief description of the commonly used classifiers in ultrasound-based CAD systems is also given. PMID:25230716

  1. Antivascular Therapy for Epithelial Ovarian Cancer

    PubMed Central

    Duhoux, Francois P.; Machiels, Jean-Pascal

    2010-01-01

    Ovarian cancer is the fifth largest cancer killer in women. Improved understanding of the molecular pathways implicated in the pathogenesis of ovarian cancer has led to the investigation of novel targeted therapies. Ovarian cancer is characterized by an imbalance between pro- and antiangiogenic factors in favor of angiogenesis activation. Various antivascular strategies are currently under investigation in ovarian cancer. They can schematically be divided into antiangiogenic and vascular-disrupting therapies. This paper provides a comprehensive review of these new treatments targeting the tumor vasculature in this disease. Promising activities have been detected in phase II trials, and results of phase III clinical trials are awaited eagerly. PMID:20072701

  2. Neonatal ovarian cysts: therapeutic dilemma.

    PubMed Central

    Widdowson, D J; Pilling, D W; Cook, R C

    1988-01-01

    Seven cases of neonatal ovarian cysts that presented over the past seven years were studied. Complications included torsion and rupture and usually occurred in cysts more than 5 cm in diameter. Surgical removal, either oophorectomy or cystectomy, was the treatment of choice. Because even cystectomy results in loss of normal ovarian tissue, and because spontaneous regression of cysts less than 5 cm in diameter can occur, a more conservative approach is now proposed. Regular ultrasonography alone is recommended if the cysts are less than 5 cm in diameter, and aspiration of the cysts followed by regular ultrasonographs if the cysts are more than 5 cm in diameter. Operation should be reserved for recurrent cysts or for those with complications. Cysts diagnosed antenatally may be aspirated in utero if there are signs of thoracic compression. Images Fig 1a Fig 1b Fig 2 PMID:3046508

  3. Bioengineering the Ovarian Follicle Microenvironment

    PubMed Central

    Shea, Lonnie D.; Woodruff, Teresa K.; Shikanov, Ariella

    2014-01-01

    Chemo- and radiation therapies used to treat cancer can have the unintended effect of making patients infertile. Clinically established fertility preservation methods, such as egg and embryo cryopreservation, are not applicable to all patients, which has motivated the development of strategies that involve ovarian tissue removal and cryopreservation before the first sterilizing treatment. To restore fertility at a later date, the early-stage follicles present in the tissue must be matured to produce functional oocytes, a process that is not possible using existing cell culture technologies. This review describes the application of tissue engineering principles to promote ovarian follicle maturation and produce mature oocytes through either in vitro culture or transplantation. The design principles for these engineered systems are presented, along with identification of emerging opportunities in reproductive biology. PMID:24849592

  4. Bioengineering the ovarian follicle microenvironment.

    PubMed

    Shea, Lonnie D; Woodruff, Teresa K; Shikanov, Ariella

    2014-07-11

    Chemo- and radiation therapies used to treat cancer can have the unintended effect of making patients infertile. Clinically established fertility preservation methods, such as egg and embryo cryopreservation, are not applicable to all patients, which has motivated the development of strategies that involve ovarian tissue removal and cryopreservation before the first sterilizing treatment. To restore fertility at a later date, the early-stage follicles present in the tissue must be matured to produce functional oocytes, a process that is not possible using existing cell culture technologies. This review describes the application of tissue engineering principles to promote ovarian follicle maturation and produce mature oocytes through either in vitro culture or transplantation. The design principles for these engineered systems are presented, along with identification of emerging opportunities in reproductive biology.

  5. Extracellular matrix in ovarian follicles.

    PubMed

    Rodgers, R J; Irving-Rodgers, H F; van Wezel, I L

    2000-05-25

    A lot is known about the control of the development of ovarian follicles by growth factors and hormones, but less is known about the roles of extracellular matrix in the control of follicular growth and development. In this review we focus on the specialized extracellular matrix of the basal laminas that are present in ovarian follicles. These include the follicular basal lamina itself, the Call-Exner bodies of the membrana granulosa, the subendothelial and arteriole smooth muscle basal laminas in the theca, and the basal lamina-like material of the thecal matrix. We discuss the evidence that during follicle development the follicular basal lamina changes in composition, that many of its components are produced by the granulosa cells, and that the follicular basal laminas of different follicles have different ultrastructural appearances, linked to the shape of the aligning granulosa cells. All these studies suggest that the follicular basal lamina is extremely dynamic during follicular development. PMID:10963877

  6. An adequate Fe nutritional status of maize suppresses infection and biotrophic growth of Colletotrichum graminicola.

    PubMed

    Ye, Fanghua; Albarouki, Emad; Lingam, Brahmasivasenkar; Deising, Holger B; von Wirén, Nicolaus

    2014-07-01

    Iron (Fe) is an essential element for plant pathogens as well as for their host plants. As Fe plays a central role in pathogen virulence, most plants have evolved Fe-withholding strategies to reduce Fe availability to pathogens. On the other hand, plants need Fe for an oxidative burst in their basal defense response against pathogens. To investigate how the plant Fe nutritional status affects plant tolerance to a hemibiotrophic fungal pathogen, we employed the maize-Colletotrichum graminicola pathosystem. Fungal infection progressed rapidly via biotrophic to necrotrophic growth in Fe-deficient leaves, while an adequate Fe nutritional status suppressed the formation of infection structures of C. graminicola already during the early biotrophic growth phase. As indicated by Prussian blue and 3,3'-diaminobenzidine (DAB) staining, the retarding effect of an adequate Fe nutritional status on fungal development coincided temporally and spatially with the recruitment of Fe to infection sites and a local production of H2 O2 . A similar coincidence between local Fe and H2 O2 accumulation was found in a parallel approach employing C. graminicola mutants affected in Fe acquisition and differing in virulence. These results indicate that an adequate Fe nutritional status delays and partially suppresses the fungal infection process and the biotrophic growth phase of C. graminicola, most likely via the recruitment of free Fe to the fungal infection site for a timely oxidative burst.

  7. Dose Limits for Man do not Adequately Protect the Ecosystem

    SciTech Connect

    Higley, Kathryn A.; Alexakhin, Rudolf M.; McDonald, Joseph C.

    2004-08-01

    It has been known for quite some time that different organisms display differing degrees of sensitivity to the effects of ionizing radiations. Some microorganisms such as the bacterium Micrococcus radiodurans, along with many species of invertebrates, are extremely radio-resistant. Humans might be categorized as being relatively sensitive to radiation, and are a bit more resistant than some pine trees. Therefore, it could be argued that maintaining the dose limits necessary to protect humans will also result in the protection of most other species of flora and fauna. This concept is usually referred to as the anthropocentric approach. In other words, if man is protected then the environment is also adequately protected. The ecocentric approach might be stated as; the health of humans is effectively protected only when the environment is not unduly exposed to radiation. The ICRP is working on new recommendations dealing with the protection of the environment, and this debate should help to highlight a number of relevant issues concerning that topic.

  8. DARHT - an `adequate` EIS: A NEPA case study

    SciTech Connect

    Webb, M.D.

    1997-08-01

    The Dual Axis Radiographic Hydrodynamic Test (DARHT) Facility Environmental Impact Statement (EIS) provides a case study that is interesting for many reasons. The EIS was prepared quickly, in the face of a lawsuit, for a project with unforeseen environmental impacts, for a facility that was deemed urgently essential to national security. Following judicial review the EIS was deemed to be {open_quotes}adequate.{close_quotes} DARHT is a facility now being built at Los Alamos National Laboratory (LANL) as part of the Department of Energy (DOE) nuclear weapons stockpile stewardship program. DARHT will be used to evaluate the safety and reliability of nuclear weapons, evaluate conventional munitions and study high-velocity impact phenomena. DARHT will be equipped with two accelerator-driven, high-intensity X-ray machines to record images of materials driven by high explosives. DARHT will be used for a variety of hydrodynamic tests, and DOE plans to conduct some dynamic experiments using plutonium at DARHT as well.

  9. ENSURING ADEQUATE SAFETY WHEN USING HYDROGEN AS A FUEL

    SciTech Connect

    Coutts, D

    2007-01-22

    Demonstration projects using hydrogen as a fuel are becoming very common. Often these projects rely on project-specific risk evaluations to support project safety decisions. This is necessary because regulations, codes, and standards (hereafter referred to as standards) are just being developed. This paper will review some of the approaches being used in these evolving standards, and techniques which demonstration projects can implement to bridge the gap between current requirements and stakeholder desires. Many of the evolving standards for hydrogen-fuel use performance-based language, which establishes minimum performance and safety objectives, as compared with prescriptive-based language that prescribes specific design solutions. This is being done for several reasons including: (1) concern that establishing specific design solutions too early will stifle invention, (2) sparse performance data necessary to support selection of design approaches, and (3) a risk-adverse public which is unwilling to accept losses that were incurred in developing previous prescriptive design standards. The evolving standards often contain words such as: ''The manufacturer shall implement the measures and provide the information necessary to minimize the risk of endangering a person's safety or health''. This typically implies that the manufacturer or project manager must produce and document an acceptable level of risk. If accomplished using comprehensive and systematic process the demonstration project risk assessment can ease the transition to widespread commercialization. An approach to adequately evaluate and document the safety risk will be presented.

  10. Belinostat and Carboplatin in Treating Patients With Recurrent or Persistent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer That Did Not Respond to Carboplatin or Cisplatin

    ClinicalTrials.gov

    2014-06-18

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

  11. Acetyl-L-Carnitine Hydrochloride in Preventing Peripheral Neuropathy in Patients With Recurrent Ovarian Epithelial Cancer, Primary Peritoneal Cavity Cancer, or Fallopian Tube Cancer Undergoing Chemotherapy

    ClinicalTrials.gov

    2014-12-29

    Fatigue; Malignant Ovarian Mixed Epithelial Tumor; Neuropathy; Neurotoxicity Syndrome; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Pain; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma

  12. Metformin Hydrochloride, Carboplatin, and Paclitaxel in Treating Patients With Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2015-05-01

    Ovarian Papillary Serous Carcinoma; Ovarian Serous Cystadenocarcinoma; Recurrent Fallopian Tube Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Primary Peritoneal Cavity Cancer

  13. KRAS Genomic Status Predicts the Sensitivity of Ovarian Cancer Cells to Decitabine.

    PubMed

    Stewart, Michelle L; Tamayo, Pablo; Wilson, Andrew J; Wang, Stephanie; Chang, Yun Min; Kim, Jong W; Khabele, Dineo; Shamji, Alykhan F; Schreiber, Stuart L

    2015-07-15

    Decitabine, a cancer therapeutic that inhibits DNA methylation, produces variable antitumor response rates in patients with solid tumors that might be leveraged clinically with identification of a predictive biomarker. In this study, we profiled the response of human ovarian, melanoma, and breast cancer cells treated with decitabine, finding that RAS/MEK/ERK pathway activation and DNMT1 expression correlated with cytotoxic activity. Further, we showed that KRAS genomic status predicted decitabine sensitivity in low-grade and high-grade serous ovarian cancer cells. Pretreatment with decitabine decreased the cytotoxic activity of MEK inhibitors in KRAS-mutant ovarian cancer cells, with reciprocal downregulation of DNMT1 and MEK/ERK phosphorylation. In parallel with these responses, decitabine also upregulated the proapoptotic BCL-2 family member BNIP3, which is known to be regulated by MEK and ERK, and heightened the activity of proapoptotic small-molecule navitoclax, a BCL-2 family inhibitor. In a xenograft model of KRAS-mutant ovarian cancer, combining decitabine and navitoclax heightened antitumor activity beyond administration of either compound alone. Our results define the RAS/MEK/DNMT1 pathway as a determinant of sensitivity to DNA methyltransferase inhibition, specifically implicating KRAS status as a biomarker of drug response in ovarian cancer.

  14. 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

  15. Biological versus chronological ovarian age: implications for assisted reproductive technology

    PubMed Central

    Alviggi, Carlo; Humaidan, Peter; Howles, Colin M; Tredway, Donald; Hillier, Stephen G

    2009-01-01

    Background Women have been able to delay childbearing since effective contraception became available in the 1960s. However, fertility decreases with increasing maternal age. A slow but steady decrease in fertility is observed in women aged between 30 and 35 years, which is followed by an accelerated decline among women aged over 35 years. A combination of delayed childbearing and reduced fecundity with increasing age has resulted in an increased number and proportion of women of greater than or equal to 35 years of age seeking assisted reproductive technology (ART) treatment. Methods Literature searches supplemented with the authors' knowledge. Results Despite major advances in medical technology, there is currently no ART treatment strategy that can fully compensate for the natural decline in fertility with increasing female age. Although chronological age is the most important predictor of ovarian response to follicle-stimulating hormone, the rate of reproductive ageing and ovarian sensitivity to gonadotrophins varies considerably among individuals. Both environmental and genetic factors contribute to depletion of the ovarian oocyte pool and reduction in oocyte quality. Thus, biological and chronological ovarian age are not always equivalent. Furthermore, biological age is more important than chronological age in predicting the outcome of ART. As older patients present increasingly for ART treatment, it will become more important to critically assess prognosis, counsel appropriately and optimize treatment strategies. Several genetic markers and biomarkers (such as anti-Müllerian hormone and the antral follicle count) are emerging that can identify women with accelerated biological ovarian ageing. Potential strategies for improving ovarian response include the use of luteinizing hormone (LH) and growth hormone (GH). When endogenous LH levels are heavily suppressed by gonadotrophin-releasing hormone analogues, LH supplementation may help to optimize treatment

  16. Developing an adequate "pneumatraumatology": understanding the spiritual impacts of traumatic injury.

    PubMed

    Bidwell, Duane R

    2002-01-01

    Psychosocial interventions and systematic theology are primary resources for chaplains and congregational pastors who care for victims of physical trauma. Yet these resources may not be adequate to address the spiritual impacts of trauma. This article proposes a preliminary "pneumatraumatology," drawing on early Christian asceticism and Buddhist mysticism to describe one way of understanding the spiritual impacts of traumatic injury. It also suggests possible responses to these impacts informed by narrative/constructionist perspectives and Breggemann's understanding of the dimensions of spiritual transformation in the Hebrew Bible.

  17. Use of Nonsteroidal Antiinflammatory Agents and Incidence of Ovarian Cancer in 2 Large Prospective Cohorts

    PubMed Central

    Tworoger, Shelley S.; Cramer, Daniel W.; Rosner, Bernard A.; Hankinson, Susan E.

    2009-01-01

    Epidemiologic data on the association between nonsteroidal antiinflammatory drugs (NSAIDs) and ovarian cancer risk have been inconsistent. The authors prospectively examined the association between regular use of aspirin and nonaspirin NSAIDs and ovarian cancer incidence among 197,486 participants of the Nurses’ Health Study (NHS) and the Nurses’ Health Study-II (NHS-II) over 24 and 16 years of follow-up, respectively. Information on aspirin was initially assessed in 1980 (NHS) and 1989 (NHS-II) and on nonaspirin NSAIDs and acetaminophen in 1990 (NHS) and 1989 (NHS-II) and updated throughout follow-up. The authors used Cox proportional hazards models adjusting for ovarian cancer risk factors. A total of 666 confirmed cases of epithelial ovarian cancer were identified over 2,790,986 person-years of follow-up. The hazard ratios associated with regular use of aspirin, nonaspirin NSAIDs, and acetaminophen were 1.11 (95% confidence interval (CI): 0.92, 1.33), 0.81 (95% CI: 0.64, 1.01), and 1.14 (95% CI: 0.92, 1.43), respectively. The authors did not observe a dose-response relation with increased frequency or duration of regular use of any of these medications and ovarian cancer incidence. The results did not differ substantially by tumor histology. In this large prospective study, the authors found no compelling evidence to support an association between regular use of aspirin, nonaspirin NSAIDs, or acetaminophen and ovarian cancer incidence. PMID:19342401

  18. Motility Related Actinin Alpha-4 Is Associated with Advanced and Metastatic Ovarian Carcinoma

    PubMed Central

    Barbolina, Maria V.; Adley, Brian P.; Kelly, David L.; Fought, Angela J.; Scholtens, Denise; Shea, Lonnie D.; Sharon Stack, M.

    2010-01-01

    Advanced and metastatic ovarian cancer is a leading cause of death from gynecologic malignancies. A more detailed understanding of the factors controlling invasion and metastasis may lead to novel anti-metastatic therapies. To model cellular interactions that occur during intraperitoneal metastasis, comparative cDNA microarray analysis and confirmatory real time RT-PCR were employed to uncover changes in gene expression that may occur in late stage ovarian cancer in response to microenvironmental cues, particularly native three-dimensional collagen I. Gene expression in human ovarian carcinoma tissues was evaluated on the RNA and protein level using real time RT-PCR and immunohistochemistry. Cell invasion and migration were evaluated in a collagen invasion assay and a scratch wound assay. Three-dimensional collagen I culture led to differential expression of several genes. The role of actinin alpha-4 (ACTN4), a cytosketeton-associated protein implicated in regulation of cell motility, was examined in detail. ACTN4 RNA and protein expression were associated with advanced and metastatic human ovarian carcinoma. This report demonstrates that a cytoskeletal-associated protein ACTN4 is upregulated by three-dimensional collagen culture conditions, leading to increased invasion and motility of ovarian cancer cells. Expression of ACTN4 in human ovarian tumors was found to be associated with advanced stage disease and peritoneal metastases. PMID:18362906

  19. CSIOVDB: a microarray gene expression database of epithelial ovarian cancer subtype.

    PubMed

    Tan, Tuan Zea; Yang, He; Ye, Jieru; Low, Jeffrey; Choolani, Mahesh; Tan, David Shao Peng; Thiery, Jean-Paul; Huang, Ruby Yun-Ju

    2015-12-22

    Databases pertaining to various diseases provide valuable resources on particular genes of interest but lack the molecular subtype and epithelial-mesenchymal transition status. CSIOVDB is a transcriptomic microarray database of 3,431 human ovarian cancers, including carcinoma of the ovary, fallopian tube, and peritoneum, and metastasis to the ovary. The database also comprises stroma and ovarian surface epithelium from normal ovary tissue, as well as over 400 early-stage ovarian cancers. This unique database presents the molecular subtype and epithelial-mesenchymal transition status for each ovarian cancer sample, with major ovarian cancer histologies (clear cell, endometrioid, mucinous, low-grade serous, serous) represented. Clinico-pathological parameters available include tumor grade, surgical debulking status, clinical response and age. The database has 1,868 and 1,516 samples with information pertaining to overall and disease-free survival rates, respectively. The database also provides integration with the copy number, DNA methylation and mutation data from TCGA. CSIOVDB seeks to provide a resource for biomarker and therapeutic target exploration for ovarian cancer research. PMID:26549805

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

    PubMed

    Luo, Shuang; Wang, Jidong; Ma, Ying; Yao, Zhenwei; Pan, Hongjuan

    2015-06-26

    miR-125b has essential roles in coordinating tumor proliferation, angiogenesis, invasiveness, metastasis and chemotherapy recurrence. In ovarian cancer miR-125b has been shown to be downregulated and acts as a tumor suppressor by targeting proto-oncogene BCL3. PPARγ, a multiple functional transcription factor, has been reported to have anti-tumor effects through inhibition of proliferation and induction of differentiation and apoptosis by targeting the tumor related genes. However, it is unclear whether miR-125b is regulated by PPARγ in ovarian cancer. In this study, we demonstrated that the miR-125b downregulated in ovarian cancer tissues and cell lines. Ligands-activated PPARγ suppressed proliferation of ovarian cancer cells and this PPARγ-induced growth inhibition is mediated by the upregulation of miR-125b. PPARγ promoted the expression of miR-125b by directly binding to the responsive element in miR-125b gene promoter region. Thus, our results suggest that PPARγ can induce growth suppression of ovarian cancer by upregulating miR-125b which inhibition of proto-oncogene BCL3. These findings will extend our understanding of the function of PPARγ in tumorigenesis and miR-125b may be a therapeutic intervention of ovarian cancer. PMID:25944662

  1. CSIOVDB: a microarray gene expression database of epithelial ovarian cancer subtype.

    PubMed

    Tan, Tuan Zea; Yang, He; Ye, Jieru; Low, Jeffrey; Choolani, Mahesh; Tan, David Shao Peng; Thiery, Jean-Paul; Huang, Ruby Yun-Ju

    2015-12-22

    Databases pertaining to various diseases provide valuable resources on particular genes of interest but lack the molecular subtype and epithelial-mesenchymal transition status. CSIOVDB is a transcriptomic microarray database of 3,431 human ovarian cancers, including carcinoma of the ovary, fallopian tube, and peritoneum, and metastasis to the ovary. The database also comprises stroma and ovarian surface epithelium from normal ovary tissue, as well as over 400 early-stage ovarian cancers. This unique database presents the molecular subtype and epithelial-mesenchymal transition status for each ovarian cancer sample, with major ovarian cancer histologies (clear cell, endometrioid, mucinous, low-grade serous, serous) represented. Clinico-pathological parameters available include tumor grade, surgical debulking status, clinical response and age. The database has 1,868 and 1,516 samples with information pertaining to overall and disease-free survival rates, respectively. The database also provides integration with the copy number, DNA methylation and mutation data from TCGA. CSIOVDB seeks to provide a resource for biomarker and therapeutic target exploration for ovarian cancer research.

  2. Tumor repressor protein 53 and steroid hormones provide a new paradigm for ovarian cancer metastases.

    PubMed

    Mullany, Lisa K; Liu, Zhilin; Wong, Kwong-Kwok; Deneke, Victoria; Ren, Yi Athena; Herron, Alan; Richards, JoAnne S

    2014-01-01

    The functional status of the tumor repressor protein (TP53 or TRP53) is a defining feature of ovarian cancer. Mutant or null alleles of TP53 are expressed in greater than 90% of all high-grade serous adenocarcinomas. Wild-type TP53 is elevated in low-grade serous adenocarcinomas in women and in our Pten;Kras;Amhr2-Cre mutant mouse model. Disruption of the Trp53 gene in this mouse model did not lead to high-grade ovarian cancer but did increase expression of estrogen receptor α (ESR1) and markedly enhanced the responsiveness of these cells to estrogen. Specifically, when Trp53-positive and Trp53 null mutant mice were treated with estradiol or vehicle, only the Trp53 null and Esr1-positive tumors respond vigorously to estradiol in vivo and exhibit features characteristic of high-grade type ovarian cancer: invasive growth into the ovarian stroma, rampant metastases to the peritoneal cavity, and nuclear atypia. Estrogen promoted and progesterone suppressed the growth of Trp53 null ovarian tumors and tumor cells injected ip, sc, or when grown in matrigel. Exposure of the Trp53 depleted cells to estrogen also has a profound impact on the tumor microenvironment and immune-related events. These results led to the new paradigm that TRP53 status is related to the susceptibility of transformed ovarian surface epithelial cells to estradiol-induced metastases and nuclear atypia via increased levels of estradiol receptor α.

  3. Genomic/Epigenomic Alterations in Ovarian Carcinoma: Translational Insight into Clinical Practice

    PubMed Central

    Dong, Anliang; Lu, Yan; Lu, Bingjian

    2016-01-01

    Ovarian carcinoma is the most lethal gynecological malignancy worldwide. Recent advance in genomic/epigenomic researches will impact on our prevention, detection and intervention on ovarian carcinoma. Detection of germline mutations in BRCA1/BRCA2, mismatch repair genes, and other genes in the homologous recombination/DNA repair pathway propelled the genetic surveillance of most hereditary ovarian carcinomas. Germline or somatic mutations in SMARCA4 in familial and sporadic small cell carcinoma of the ovary, hypercalcemia type, lead to our recognition on this rare aggressive tumor as a new entity of the atypical teratoma/rhaboid tumor family. Genome-wide association studies have identified many genetic variants that will contribute to the evaluation of ovarian carcinoma risk and prognostic prediction. Whole exome sequencing and whole genome sequencing discovered rare mutations in other drive mutations except p53, but demonstrated the presence of high genomic heterogeneity and adaptability in the genetic evolution of high grade ovarian serous carcinomas that occurs in cancer progression and chemotherapy. Gene mutations, copy number aberrations and DNA methylations provided promising biomarkers for the detection, diagnosis, prognosis, therapy response and targets of ovarian cancer. These findings underscore the necessity to translate these potential biomarkers into clinical practice. PMID:27471560

  4. Soy and isoflavone intake associated with reduced risk of ovarian cancer in southern Chinese women.

    PubMed

    Lee, Andy H; Su, Dada; Pasalich, Maria; Tang, Li; Binns, Colin W; Qiu, Liqian

    2014-04-01

    Isoflavones, mainly found in soy, have been shown to inhibit ovarian cancer cell proliferation. We hypothesized that soy consumption and isoflavone intake are related to the risk of ovarian cancer. A case-control study was conducted in southern China to ascertain this hypothesis. Five hundred incident patients with histologically confirmed cancer of the ovary and 500 controls (mean age 59 years) were recruited from four public hospitals in Guangzhou. Information on habitual consumption of soy foods, including soybean, soy milk, fresh tofu, dried tofu, and soybean sprout, was obtained face-to-face from participants through a validated and reliable semi-quantitative food frequency questionnaire. Isoflavone intakes were then estimated using the USDA nutrient database. The ovarian cancer patients reported lower consumption levels of individual and total soy foods (75.3 ± 53.6 g/day) compared to the controls (110.7 ± 88.8 g/day). Logistic regression analyses showed that regular intake of soy foods could reduce the ovarian cancer risk, the adjusted odds ratio being 0.29 (95% confidence interval 0.20 to 0.42) for women who consumed at least 120 g/day relative to those less than 61 g/day. Similarly, isoflavone intakes were inversely associated with the ovarian cancer risk, with significant dose-response relationships (P < 0.001). We concluded that consumption of soy foods is associated with a reduced risk of ovarian cancer in southern Chinese women.

  5. Intended care seeking for ovarian cancer symptoms among U.S. women.

    PubMed

    Cooper, Crystale Purvis; Gelb, Cynthia A; Trivers, Katrina F; Stewart, Sherri L

    2016-06-01

    To investigate U.S. women's intended care seeking for symptoms associated with ovarian cancer, data from the 2012 HealthStyles Fall survey of U.S. adults were examined. Analyses were limited to women with no history of gynecologic cancer (N = 1726). Logistic regression models for intended care seeking within 2 weeks of symptom onset were developed. A minority of women recognized that unexplained pelvic or abdominal pain (29.9%), unexplained bloating (18.1%), and feeling full after eating a small amount of food (10.1%) can indicate ovarian cancer, and 31.1% mistakenly believed that the Papanicolaou (Pap) test screens for the disease. In the multivariate regression models, the most consistent, significant predictors (p < 0.01) of intended care seeking within 2 weeks of symptom onset were age (older women were more likely to seek care) and awareness that symptoms could signal ovarian cancer. Care seeking in response to ovarian cancer symptoms may be delayed among younger women and those who do not recognize the potential significance of symptoms. Raising awareness of ovarian cancer symptoms may promote early detection. However, educational efforts should emphasize that symptoms associated with ovarian cancer may also result from benign conditions. PMID:27419020

  6. BET Bromodomain Inhibition as a Therapeutic Strategy in Ovarian Cancer by Downregulating FoxM1.

    PubMed

    Zhang, Zhenfeng; Ma, Pengfei; Jing, Ying; Yan, Ying; Cai, Mei-Chun; Zhang, Meiying; Zhang, Shengzhe; Peng, Huixin; Ji, Zhi-Liang; Di, Wen; Gu, Zhenyu; Gao, Wei-Qiang; Zhuang, Guanglei

    2016-01-01

    Ovarian cancer is responsible for the highest mortality among all gynecologic malignancies, and novel therapies are urgently needed to improve patient outcome. Here we performed an integrative genomic analysis and identified the bromodomain and extraterminal domain (BET) protein BRD4 as a potential therapeutic target in ovarian cancer. Suppression of BRD4 using small-molecule BET inhibitors JQ1 and I-BET151, or dual kinase-bromodomain inhibitor volasertib, led to robust and broad antitumor effects across all subclasses of ovarian cancer. In contrast to many other cancers which are susceptible to BET inhibition due to downregulation of super-enhancer-dependent MYC transcript, we discovered that JQ1-sensitive ovarian cancer cells exhibited marked disruption of Forkhead box protein M1 (FoxM1) pathway, a key driver of ovarian carcinoma. These in vitro findings were further supported by in vivo efficacies of JQ1 targeting both cell line-based and patient-derived xenograft models. Our data establish a new treatment strategy against ovarian cancer by employing epigenetic vulnerabilities, and provide a mechanistic rationale for the clinical investigation of BET bromodomain inhibitors in this deadly disease. PMID:26877780

  7. Maximal expression of Foxl2 in pituitary gonadotropes requires ovarian hormones.

    PubMed

    Herndon, Maria K; Nilson, John H

    2015-01-01

    Gonadotropin-releasing hormone (GnRH) and activin regulate synthesis of FSH and ultimately fertility. Recent in vivo studies cast SMAD4 and FOXL2 as master transcriptional mediators of activin signaling that act together and independently of GnRH to regulate Fshb gene expression and female fertility. Ovarian hormones regulate GnRH and its receptor (GNRHR) through negative and positive feedback loops. In contrast, the role of ovarian hormones in regulating activin, activin receptors, and components of the activin signaling pathway, including SMAD4 and FOXL2, remains understudied. The widespread distribution of activin and many of its signaling intermediates complicates analysis of the effects of ovarian hormones on their synthesis in gonadotropes, one of five pituitary cell types. We circumvented this complication by using a transgenic model that allows isolation of polyribosomes selectively from gonadotropes of intact females and ovariectomized females treated with or without a GnRH antagonist. This paradigm allows assessment of ovarian hormonal feedback and distinguishes responses that are either independent or dependent on GnRH. Surprisingly, our results indicate that Foxl2 levels in gonadotropes decline significantly in the absence of ovarian input and independently of GnRH. Expression of the genes encoding other members of the activin signaling pathway are unaffected by loss of ovarian hormonal feedback, highlighting their selective effect on Foxl2. Expression of Gnrhr, a known target of FOXL2, also declines upon ovariectomy consistent with reduced expression of Foxl2 and loss of ovarian hormones. In contrast, Fshb mRNA increases dramatically post-ovariectomy due to increased compensatory input from GnRH. Together these data suggest that ovarian hormones regulate expression of Foxl2 thereby expanding the number of genes controlled by the hypothalamic-pituitary-gonadal axis that ultimately dictate reproductive fitness.

  8. 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.

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

    SciTech Connect

    Luo, Shuang; Wang, Jidong; Ma, Ying; Yao, Zhenwei; Pan, Hongjuan

    2015-06-26

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

  10. On Adequate Comparisons of Antenna Phase Center Variations

    NASA Astrophysics Data System (ADS)

    Schoen, S.; Kersten, T.

    2013-12-01

    One important part for ensuring the high quality of the International GNSS Service's (IGS) products is the collection and publication of receiver - and satellite antenna phase center variations (PCV). The PCV are crucial for global and regional networks, since they introduce a global scale factor of up to 16ppb or changes in the height component with an amount of up to 10cm, respectively. Furthermore, antenna phase center variations are also important for precise orbit determination, navigation and positioning of mobile platforms, like e.g. the GOCE and GRACE gravity missions, or for the accurate Precise Point Positioning (PPP) processing. Using the EUREF Permanent Network (EPN), Baire et al. (2012) showed that individual PCV values have a significant impact on the geodetic positioning. The statements are further supported by studies of Steigenberger et al. (2013) where the impact of PCV for local-ties are analysed. Currently, there are five calibration institutions including the Institut für Erdmessung (IfE) contributing to the IGS PCV file. Different approaches like field calibrations and anechoic chamber measurements are in use. Additionally, the computation and parameterization of the PCV are completely different within the methods. Therefore, every new approach has to pass a benchmark test in order to ensure that variations of PCV values of an identical antenna obtained from different methods are as consistent as possible. Since the number of approaches to obtain these PCV values rises with the number of calibration institutions, there is the necessity for an adequate comparison concept, taking into account not only the numerical values but also stochastic information and computational issues of the determined PCVs. This is of special importance, since the majority of calibrated receiver antennas published by the IGS origin from absolute field calibrations based on the Hannover Concept, Wübbena et al. (2000). In this contribution, a concept for the adequate

  11. Improving access to adequate pain management in Taiwan.

    PubMed

    Scholten, Willem

    2015-06-01

    There is a global crisis in access to pain management in the world. WHO estimates that 4.65 billion people live in countries where medical opioid consumption is near to zero. For 2010, WHO considered a per capita consumption of 216.7 mg morphine equivalents adequate, while Taiwan had a per capita consumption of 0.05 mg morphine equivalents in 2007. In Asia, the use of opioids is sensitive because of the Opium Wars in the 19th century and for this reason, the focus of controlled substances policies has been on the prevention of diversion and dependence. However, an optimal public health outcome requires that also the beneficial aspects of these substances are acknowledged. Therefore, WHO recommends a policy based on the Principle of Balance: ensuring access for medical and scientific purposes while preventing diversion, harmful use and dependence. Furthermore, international law requires that countries ensure access to opioid analgesics for medical and scientific purposes. There is evidence that opioid analgesics for chronic pain are not associated with a major risk for developing dependence. Barriers for access can be classified in the categories of overly restrictive laws and regulations; insufficient medical training on pain management and problems related to assessment of medical needs; attitudes like an excessive fear for dependence or diversion; and economic and logistical problems. The GOPI project found many examples of such barriers in Asia. Access to opioid medicines in Taiwan can be improved by analysing the national situation and drafting a plan. The WHO policy guidelines Ensuring Balance in National Policies on Controlled Substances can be helpful for achieving this purpose, as well as international guidelines for pain treatment.

  12. Are women with psychosis receiving adequate cervical cancer screening?

    PubMed Central

    Tilbrook, Devon; Polsky, Jane; Lofters, Aisha

    2010-01-01

    ABSTRACT OBJECTIVE To investigate the rates of cervical cancer screening among female patients with psychosis compared with similar patients without psychosis, as an indicator of the quality of primary preventive health care. DESIGN A retrospective cohort study using medical records between November 1, 2004, and November 1, 2007. SETTING Two urban family medicine clinics associated with an academic hospital in Toronto, Ont. PARTICIPANTS A random sample of female patients with and without psychosis between the ages of 20 and 69 years. MAIN OUTCOME MEASURES Number of Papanicolaou tests in a 3-year period. RESULTS Charts for 51 female patients with psychosis and 118 female patients without psychosis were reviewed. Of those women with psychosis, 62.7% were diagnosed with schizophrenia, 19.6% with bipolar disorder, 17.6% with schizoaffective disorder, and 29.4% with other psychotic disorders. Women in both groups were similar in age, rate of comorbidities, and number of full physical examinations. Women with psychosis were significantly more likely to smoke (P < .0001), to have more primary care appointments (P = .035), and to miss appointments (P = .0002) than women without psychosis. After adjustment for age, other psychiatric illnesses, number of physical examinations, number of missed appointments, and having a gynecologist, women with psychosis were significantly less likely to have had a Pap test in the previous 3 years compared with women without psychosis (47.1% vs 73.7%, respectively; odds ratio 0.19, 95% confidence interval 0.06 to 0.58). CONCLUSION Women with psychosis are more than 5 times less likely to receive adequate Pap screening compared with the general population despite their increased rates of smoking and increased number of primary care visits. PMID:20393098

  13. Improving access to adequate pain management in Taiwan.

    PubMed

    Scholten, Willem

    2015-06-01

    There is a global crisis in access to pain management in the world. WHO estimates that 4.65 billion people live in countries where medical opioid consumption is near to zero. For 2010, WHO considered a per capita consumption of 216.7 mg morphine equivalents adequate, while Taiwan had a per capita consumption of 0.05 mg morphine equivalents in 2007. In Asia, the use of opioids is sensitive because of the Opium Wars in the 19th century and for this reason, the focus of controlled substances policies has been on the prevention of diversion and dependence. However, an optimal public health outcome requires that also the beneficial aspects of these substances are acknowledged. Therefore, WHO recommends a policy based on the Principle of Balance: ensuring access for medical and scientific purposes while preventing diversion, harmful use and dependence. Furthermore, international law requires that countries ensure access to opioid analgesics for medical and scientific purposes. There is evidence that opioid analgesics for chronic pain are not associated with a major risk for developing dependence. Barriers for access can be classified in the categories of overly restrictive laws and regulations; insufficient medical training on pain management and problems related to assessment of medical needs; attitudes like an excessive fear for dependence or diversion; and economic and logistical problems. The GOPI project found many examples of such barriers in Asia. Access to opioid medicines in Taiwan can be improved by analysing the national situation and drafting a plan. The WHO policy guidelines Ensuring Balance in National Policies on Controlled Substances can be helpful for achieving this purpose, as well as international guidelines for pain treatment. PMID:26068436

  14. Mammaglobin B (SCGB2A1) is a novel tumour antigen highly differentially expressed in all major histological types of ovarian cancer: implications for ovarian cancer immunotherapy

    PubMed Central

    Bellone, S; Tassi, R; Betti, M; English, D; Cocco, E; Gasparrini, S; Bortolomai, I; Black, J D; Todeschini, P; Romani, C; Ravaggi, A; Bignotti, E; Bandiera, E; Zanotti, L; Pecorelli, S; Ardighieri, L; Falchetti, M; Donzelli, C; Siegel, E R; Azodi, M; Silasi, D-A; Ratner, E; Schwartz, P E; Rutherford, T J; Santin, A D

    2013-01-01

    Background: We studied the genetic fingerprints of ovarian cancer and validated the potential of Mammaglobin b (SCGB2A1), one of the top differentially expressed genes found in our analysis, as a novel ovarian tumour rejection antigen. Methods: We profiled 70 ovarian carcinomas including 24 serous (OSPC), 15 clear-cell (CC), 24 endometrioid (EAC) and 7 poorly differentiated tumours, and 14 normal human ovarian surface epithelial (HOSE) control cell lines using the Human HG-U133 Plus 2.0 chip (Affymetrix). Quantitative real-time PCR and immunohistochemistry staining techniques were used to validate microarray data at RNA and protein levels for SCGB2A1. Full-length human-recombinant SCGB2A1 was used to pulse monocyte-derived dendritic cells (DCs) to stimulate autologous SCGB2A1-specific cytotoxic T-lymphocyte (CTL) responses against chemo-naive and chemo-resistant autologous ovarian tumours. Results: Gene expression profiling identified SCGB2A1 as a top differentially expressed gene in all histological ovarian cancer types tested. The CD8+ CTL populations generated against SCGB2A1 were able to consistently induce lysis of autologous primary (chemo-naive) and metastatic/recurrent (chemo-resistant) target tumour cells expressing SCGB2A1, whereas autologous HLA-identical noncancerous cells were not lysed. Cytotoxicity against autologous tumour cells was significantly inhibited by anti-HLA-class I (W6/32) monoclonal antibody. Intracellular cytokine expression measured by flow cytometry showed a striking type 1 cytokine profile (i.e., high IFN-γ secretion) in SCGB2A1-specific CTLs. Conclusion: SCGB2A1 is a top differentially expressed gene in all major histological types of ovarian cancers and may represent a novel and attractive target for the immunotherapy of patients harbouring recurrent disease resistant to chemotherapy. PMID:23807163

  15. Genetically modified mouse models for premature ovarian failure (POF).

    PubMed

    Jagarlamudi, Krishna; Reddy, Pradeep; Adhikari, Deepak; Liu, Kui

    2010-02-01

    Premature ovarian failure (POF) is a complex disorder that affects approximately 1% of women. POF is characterized by the depletion of functional ovarian follicles before the age of 40 years, and clinically, patients may present with primary amenorrhea or secondary amenorrhea. Although some genes have been hypothesized to be candidates responsible for POF, the etiology of most of the cases is idiopathic, with the underlying causes still unidentified because of the heterogeneity of the disease. In this review, we consider some mutant mouse models that exhibit phenotypes which are comparable to human POF, and we suggest that the use of these mouse models may help us to gain a better understanding of the molecular mechanisms underlying POF in humans.

  16. Benign epithelial ovarian tumours-cancer precursors or markers for ovarian cancer risk?

    PubMed

    Jordan, Susan; Green, Adèle; Webb, Penelope

    2006-06-01

    The natural history of the development of epithelial ovarian cancer remains obscure and no effective screening test exists. In several human malignancies progression from benign to invasive tumour occurs, but this sequence has not been established for epithelial ovarian cancer. We have reviewed epidemiological, histopathological and molecular studies of benign epithelial ovarian tumours to assess the evidence for and against such a progression in ovarian cancer. These data suggest that a diagnosis of a benign ovarian cyst or tumour is associated with an increased risk of ovarian cancer later in life. Current evidence also suggests that benign serous tumours can progress to low-grade serous cancer and that benign mucinous tumours can progress to mucinous cancer. The more common high-grade serous ovarian cancers are likely to arise de novo.

  17. Clomiphene citrate challenge test in the assessment of ovarian reserve before controlled ovarian hyperstimulation for intracytoplasmic sperm injection.

    PubMed

    Kahraman, S; Vicdan, K; Işik, A Z; Ozgün, O D; Alaybeyoğlu, L; Polat, G; Biberoğlu, K

    1997-06-01

    The objective of this study is to evaluate the performance of clomiphene citrate (CC) challenge test to predict diminished ovarian reserve before controlled ovarian hyperstimulation for intracytoplasmic sperm injection (ICSI). The 198 women who underwent the CC challenge test fulfilled the following criteria; over 35 years of age, removal of one ovary or previous ovarian surgery, the presence of ovarian endometrioma or previous poor response to ovarian hyperstimulation. Of the patients tested, 141 were found to have a normal CC challenge test while 57 had an abnormal result. The cancellation rate of the cycle with a poor response was significantly higher in women with an abnormal test (36.8%) than in those with a normal test (19.8%) (P < 0.05). The sensitivity of CC test for cycle cancellation was found to be 43% with a specificity of 76%, positive and negative predictive values of 37 and 80%, respectively. The estradiol values on hCG day, the number of retrieved oocytes and metaphase II oocytes and the rate of transfer cycles were significantly lower in females with an abnormal test. Women with normal test results had higher pregnancy rates per embryo transfer than those with abnormal test results (21.5 vs. 13.3%) and the predictive value of an abnormal test for failing to conceive was 93% (53/57) with a sensitivity of 31%, specificity of 84% and negative predictive value of 15.6%. Of 57 women with an abnormal test result, 25 (43.8%) were abnormal due only to an elevated day 10 or 11 value of FSH, which could not be detected using only basal FSH screening. In this group, the cancellation rate (48 vs. 19.8%, P < 0.01), the rate of transfer cycles (48 vs. 72.3%, P < 0.05) and the mean number of retrieved oocytes (4.9 +/- 2.5 vs. 6.4 +/- 3.1, P < 0.01) were all significantly different from normal test group. Although the rate of pregnancies per started cycle (8 vs. 15.6%) did not show a statistically significant difference, this is most probably due to the low number

  18. MV-NIS or Investigator's Choice Chemotherapy in Treating Patients With Ovarian, Fallopian, or Peritoneal Cancer

    ClinicalTrials.gov

    2016-06-24

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

  19. [Status report on the chemotherapy of ovarian cancer at special cancer centers in Hungary (2002-2003)].

    PubMed

    Pulay, Tamás; Baki, Márta; Bodoky, György; Dank, Magdolna; Cseh, József; Csejtei, András; Csömör, Sándor; Erfán, József; Esik, Olga; Faluhelyi, Zsolt; Izsó, József; Hernádi, Zoltán; Kammerer, Kinga; Krommer, Károly; Magyar, Tamás; Mayer, Arpád; Megyery, Eva; Moskovits, Katalin; Pécsi, Lajos; Pikó, Béla; Pintér, Tamás; Ruzsa, Agnes; Szánthó, András; Szántó, István; Szántó, János; Szucs, Miklós; Tálos, Zsuzsanna; Thurzó, László; Kásler, Miklós

    2004-01-01

    Data on the first-line treatment of ovarian cancer in special centers of Hungary 2002 and 2003 are presented, involving 283 and 416 patients, respectively. Patients' age, clinical stage and histological type of the tumor were highly similar to literature data, while grades were different. Surgical effectiveness in case of IIIc staged tumors with >1 cm residual mass was 37%. The ratio of interval laparotomy was about 15%. Overall response rates of the first-line treatment of ovarian cancer was 82%, while the rate of complete remissions was 60%. The authors provide detailed analysis of factors that can improve the chemotherapy of ovarian cancer in Hungary.

  20. Ganglionic adrenergic action modulates ovarian steroids and nitric oxide in prepubertal rat.

    PubMed

    Delgado, Silvia Marcela; Casais, Marilina; Sosa, Zulema; Rastrilla, Ana María

    2006-08-01

    Both peripheral innervation and nitric oxide (NO) participate in ovarian steroidogenesis. The purpose of this work was to analyse the ganglionic adrenergic influence on the ovarian release of steroids and NO and the possible steroids/NO relationship. The experiments were carried out in the ex vivo coeliac ganglion-superior ovarian nerve (SON)-ovary system of prepubertal rats. The coeliac ganglion-SON-ovary system was incubated in Krebs Ringer-bicarbonate buffer in presence of adrenergic agents in the ganglionic compartment. The accumulation of progesterone, androstenedione, oestradiol and NO in the ovarian incubation liquid was measured. Norepinephrine in coeliac ganglion inhibited the liberation of progesterone and increased androstenedione, oestradiol and NO in ovary. The addition of alpha and beta adrenergic antagonists also showed different responses in the liberation of the substances mentioned before, which, from a physiological point of view, reveals the presence of adrenergic receptors in coeliac ganglion. In relation to propranolol, it does not revert the effect of noradrenaline on the liberation of progesterone, which leads us to think that it might also have a "per se" effect on the ganglion, responsible for the ovarian response observed for progesterone. Finally, we can conclude that the ganglionic adrenergic action via SON participates on the regulation of the prepubertal ovary in one of two ways: either increasing the NO, a gaseous neurotransmitter with cytostatic characteristics, to favour the immature follicles to remain dormant or increasing the liberation of androstenedione and oestradiol, the steroids necessary for the beginning of the near first estral cycle.

  1. Preliminary results suggesting exaggerated ovarian androgen production early in the course of polycystic ovary syndrome.

    PubMed

    Francis, G L; Getts, A; McPherson, J C

    1990-11-01

    Excess ovarian androgen production might be a cause of the polycystic ovary syndrome (PCO). Previous studies have evaluated adult women with long-standing abnormality of the hypothalamic-pituitary gonadal axis. Abnormal ovarian function in such patients could be a primary or even a secondary finding. For that reason, this study was designed to evaluate ovarian androgen production in symptomatic adolescent females. Simultaneous adrenal suppression, by using dexamethasone, and ovarian stimulation, by using gonadotropin-releasing hormone (GnRH), were achieved in 12 patients. Following stimulation, blood was serially obtained over 8 hr to measure gonadotropin, estrogen, and androgen responses. Based on the androgen response, patients could be divided into two groups. Group A (five) had a significant increase (p less than 0.01) in free testosterone, whereas group B (seven) had no increase in any androgen, including free testosterone (significantly different from group A, p = 0.01). All patients in group A had enlarged or cystic ovaries, whereas only one-quarter patients in group B had enlarged ovaries (significantly different from group A, p less than 0.03). The pituitary and estrogenic response was similar in both groups. These preliminary data suggest that some patients with PCO (group A) have a primary abnormality in ovarian androgen production early in the course of their disease.

  2. The Alchemy of "Costing Out" an Adequate Education

    ERIC Educational Resources Information Center

    Hanushek, Eric A.

    2006-01-01

    In response to the rapid rise in court cases related to the adequacy of school funding, a variety of alternative methods have been developed to provide an analytical base about the necessary expenditure on schools. These approaches have been titled to give an aura of a thoughtful and solid scientific basis: the professional judgment model, the…

  3. The Cancer Genome Atlas ovarian cancer analysis

    Cancer.gov

    An analysis of genomic changes in ovarian cancer has provided the most comprehensive and integrated view of cancer genes for any cancer type to date. Ovarian serous adenocarcinoma tumors from 500 patients were examined by The Cancer Genome Atlas (TCGA) Re

  4. Gene Expression Patterns in Ovarian Carcinomas

    PubMed Central

    Schaner, Marci E.; Ross, Douglas T.; Ciaravino, Giuseppe; Sørlie, Therese; Troyanskaya, Olga; Diehn, Maximilian; Wang, Yan C.; Duran, George E.; Sikic, Thomas L.; Caldeira, Sandra; Skomedal, Hanne; Tu, I-Ping; Hernandez-Boussard, Tina; Johnson, Steven W.; O'Dwyer, Peter J.; Fero, Michael J.; Kristensen, Gunnar B.; Børresen-Dale, Anne-Lise; Hastie, Trevor; Tibshirani, Robert; van de Rijn, Matt; Teng, Nelson N.; Longacre, Teri A.; Botstein, David; Brown, Patrick O.; Sikic, Branimir I.

    2003-01-01

    We used DNA microarrays to characterize the global gene expression patterns in surface epithelial cancers of the ovary. We identified groups of genes that distinguished the clear cell subtype from other ovarian carcinomas, grade I and II from grade III serous papillary carcinomas, and ovarian from breast carcinomas. Six clear cell carcinomas were distinguished from 36 other ovarian carcinomas (predominantly serous papillary) based on their gene expression patterns. The differences may yield insights into the worse prognosis and therapeutic resistance associated with clear cell carcinomas. A comparison of the gene expression patterns in the ovarian cancers to published data of gene expression in breast cancers revealed a large number of differentially expressed genes. We identified a group of 62 genes that correctly classified all 125 breast and ovarian cancer specimens. Among the best discriminators more highly expressed in the ovarian carcinomas were PAX8 (paired box gene 8), mesothelin, and ephrin-B1 (EFNB1). Although estrogen receptor was expressed in both the ovarian and breast cancers, genes that are coregulated with the estrogen receptor in breast cancers, including GATA-3, LIV-1, and X-box binding protein 1, did not show a similar pattern of coexpression in the ovarian cancers. PMID:12960427

  5. How Ovarian Cancer Evades Immune Scrutiny.

    PubMed

    Poh, Alissa

    2016-04-01

    Although dendritic cells are abundant in ovarian tumors, scientists have been puzzled that these cells aren't immunostimulatory. New research reveals a role for the protein SATB1, which is transiently required during ovarian-associated dendritic cell maturation-its unremitting expression in these cells drives them to acquire an inflammatory, immunosuppressive phenotype.

  6. Intraoperative Hyperthermic Intraperitoneal Chemotherapy in Patients With Advanced Ovarian Cancer.

    PubMed

    Oseledchyk, Anton; Zivanovic, Oliver

    2015-09-01

    Ovarian cancer, because it is largely confined to the peritoneal cavity, has a unique tumor biology and metastatic spread pattern. Its metastatic potential comes from detached tumor cells in the peritoneal cavity that re-attach to the mesothelial lining of the peritoneal surface. It is proposed that these micrometastases without neovasculature, as well as floating malignant cells, are drivers of early recurrence, since they can be neither resected nor adequately treated by systemic chemotherapy. This represents the major rationale for local treatment by means of postoperative intraperitoneal (IP) chemotherapy, which is the standard of care in the United States in patients with advanced-stage ovarian cancer who have minimal residual disease following cytoreductive surgery. An alternative loco-regional treatment strategy is the "HIPEC" procedure--hyperthermic IP chemoperfusion that is performed during the operation immediately following completion of gross tumor resection, and which provides improved tissue penetration and distribution of the chemotherapeutics. However, prospective data are limited and an outcomes benefit has yet to be shown. Here we discuss the advantages and pitfalls of HIPEC, as well as current data and ongoing prospective trials. PMID:26384807

  7. Ovarian serous carcinogenesis from tubal secretory cells.

    PubMed

    Zhang, Wenjing; Wei, Linxuan; Li, Lingmin; Yang, Binlie; Kong, Beihua; Yao, Guang; Zheng, Wenxin

    2015-11-01

    Due to a poor understanding of tumorigenesis, ovarian cancers remain the most lethal gynecologic malignancy and cause horrific deaths. In the last decade, a new dualistic model for ovarian cancer was proposed, wherein ovarian serous cancers are classified as either high-grade or low-grade, with each having different tumorigenic processes, and pathologic and clinical features. Surprisingly, both high- and low-grade ovarian serous cancers were recently found to originate not in the ovaries, but rather from the secretory cells of the fallopian tube, mostly from the tubal fimbriated ends. In this article, we review the evidentiary basis for the aforementioned paradigm shift in the cell origin of ovarian serous cancers, as well as its potential clinical implications. PMID:26174492

  8. Ovarian cancer mortality and industrial pollution.

    PubMed

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

    2015-10-01

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

  9. OVARIAN CANCER: INVOLVEMENT OF THE MATRIX METALLOPROTEINASES

    PubMed Central

    Al-Alem, Linah; Curry, Thomas E.

    2016-01-01

    Ovarian cancer is the leading cause of death from gynecologic malignancies. Reasons for the high mortality rate associated with ovarian cancer include a late diagnosis at which time the cancer has metastasized throughout the peritoneal cavity. Cancer metastasis is facilitated by the remodeling of the extracellular tumor matrix by a family of proteolytic enzymes known as the matrix metalloproteinases (MMPs). There are 23 members in the MMP family, many of which have been reported to be associated with ovarian cancer. In the current paradigm, ovarian tumor cells and the surrounding stromal cells stimulate the synthesis and/or activation of various MMPs to aid in tumor growth, invasion, and eventual metastasis. This review sheds light on the different MMPs in the various types of ovarian cancer and their impact on the progression of this gynecologic malignancy. PMID:25918438

  10. [Evidence-based therapy of polycystic ovarian syndrome].

    PubMed

    Gődény, Sándor; Csenteri, Orsolya Karola

    2015-11-01

    Polycystic ovary syndrome is recognized as the most common hormonal and metabolic disorder likely to affect women. The heterogeneous endocrinopathy is characterized by clinical and/or biochemical hyperandrogenism, oligo- or amenorrhoea, anovulatory infertility, and polycystic ovarian morphology. The syndrome is often associated with obesity, hyperinsulinemia and adversely affects endocrine, metabolic, and cardiovascular health. The symptoms and complaint of the patients vary with age. To maximise health gain of the syndrome, adequate, evidence based effective, efficient and safe treatment is necessary. This article summarises the highest available evidence provided by studies, meta-analysis and systematic reviews about the therapeutical possibilities for treating obesity, hyperandrogenism, menstrual abnormalities, infertility and psychological problems related to polycystic ovary syndrome.

  11. Maintaining Adequate CO2 Washout for an Advanced EMU via a New Rapid Cycle Amine Technology

    NASA Technical Reports Server (NTRS)

    Chullen, Cinda; Conger, Bruce

    2012-01-01

    Over the past several years, NASA has realized tremendous progress in Extravehicular Activity (EVA) technology development. This has been evidenced by the progressive development of a new Rapid Cycle Amine (RCA) system for the Advanced Extravehicular Mobility Unit (AEMU) Portable Life Support Subsystem (PLSS). The PLSS is responsible for the life support of the crew member in the spacesuit. The RCA technology is responsible for carbon dioxide (CO2) and humidity control. Another aspect of the RCA is that it is on-back vacuum-regenerable, efficient, and reliable. The RCA also simplifies the PLSS schematic by eliminating the need for a condensing heat exchanger for humidity control in the current EMU. As development progresses on the RCA, it is important that the sizing be optimized so that the demand on the PLSS battery is minimized. As well, maintaining the CO2 washout at adequate levels during an EVA is an absolute requirement of the RCA and associated ventilation system. Testing has been underway in-house at NASA Johnson Space Center and analysis has been initiated to evaluate whether the technology provides exemplary performance in ensuring that the CO2 is removed sufficiently and the ventilation flow is adequate for maintaining CO2 washout in the AEMU spacesuit helmet of the crew member during an EVA. This paper will review the recent developments of the RCA unit, testing planned in-house with a spacesuit simulator, and the associated analytical work along with insights from the medical aspect on the testing. 1

  12. PET Imaging of Ovarian Carcinoma With 18F-FSPG

    ClinicalTrials.gov

    2016-08-16

    Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer

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

    Cancer.gov

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

  14. [Presumed benign ovarian tumors during pregnancy].

    PubMed

    Tariel, O; Huissoud, C; Rudigoz, R C; Dubernard, G

    2013-12-01

    The incidence of ovarian tumors diagnosed during pregnancy is between 0.3 and 5.4% (LE2). The most common ovarian tumors diagnosed during pregnancy are functional cysts diagnosed incidentally during the first trimester ultrasound (LE2) and spontaneous regression is often observed. Dermoid cysts and cystadenoma are the most frequent organic benign ovarian tumors diagnosed during pregnancy (LE2). The main complication of presumed benign ovarian tumor (PBOT) during pregnancy is adnexal torsion and is estimated at around 8% (LE2), especially at the end of the first trimester and during the second trimester (LE4). Tumor markers are not reliable during pregnancy to assess the risk of malignancy of ovarian tumor (LE2). Ultrasound remains the gold standard for characterizing an ovarian tumor during pregnancy (LE3), but with a lower specificity for the diagnosis of malignancy. Pelvic MRI is accurate in the diagnosis of ovarian tumors during pregnancy and brings additional information to ultrasound (LE4). Ultrasound-guided aspiration of ovarian tumors is not recommended during pregnancy (grade C). Expectation is recommended in cases of PBOT during pregnancy, which does not enlarge (grade C). Whatever the gestational age, surgery is recommended in patients with symptoms suggesting an adnexal torsion (grade C). Laparoscopy is possible during the first and second trimester of pregnancy for the management of symptomatic PBOT (LE3). The risk of miscarriage following surgery (laparoscopy and laparotomy) for ovarian tumor during pregnancy is estimated at 2.8% (LE3). The route of delivery should not be modified by the ovarian tumour, except in case of praevia cyst requiring a cesarean section, a complication or suspicion of malignancy (grade C). Surgical treatment of PBOT may be performed during a cesarean section indicated for another reason. The risk of torsion is increased during the postpartum period (LE4).

  15. Oncolytic reovirus against ovarian and colon cancer.

    PubMed

    Hirasawa, Kensuke; Nishikawa, Sandra G; Norman, Kara L; Alain, Tommy; Kossakowska, Anna; Lee, Patrick W K

    2002-03-15

    Reovirus selectively replicates in and destroys cancer cells with an activated Ras signaling pathway. In this study, we evaluated the feasibility of using reovirus (serotype 3, strain Dearing) as an antihuman colon and ovarian cancer agent. In in vitro studies, reovirus infection in human colon and ovarian cell lines was assessed by cytopathic effect as detected by light microscopy, [(35)S]Methionine labeling of infected cells for viral protein synthesis and progeny virus production by plaque assay. We observed that reovirus efficiently infected all five human colon cancer cell lines (Caco-2, DLD-1, HCT-116, HT-29, and SW48) and four human ovarian cancer cell lines (MDAH2774, PA-1, SKOV3, and SW626) which were tested, but not a normal colon cell line (CCD-18Co) or a normal ovarian cell line (NOV-31). We also observed that the Ras activity in the human colon and ovarian cancer cell lines was elevated compared with that in normal colon and ovarian cell lines. In animal models, intraneoplastic as well as i.v. inoculation of reovirus resulted in significant regression of established s.c. human colon and ovarian tumors implanted at the hind flank. Histological studies revealed that reovirus infection in vivo was restricted to tumor cells, whereas the surrounding normal tissue remained uninfected. Additionally, in an i.p. human ovarian cancer xenograft model, inhibition of ascites tumor formation and the survival of animals treated with live reovirus was significantly greater than of control mice treated with UV-inactivated reovirus. Reovirus infection in ex vivo primary human ovarian tumor surgical samples was also confirmed, further demonstrating the potential of reovirus therapy. These results suggest that reovirus holds promise as a novel agent for human colon and ovarian cancer therapy. PMID:11912142

  16. Adequate iron stores and the 'Nil nocere' principle.

    PubMed

    Hollán, S; Johansen, K S

    1993-01-01

    There is a need to change the policy of unselective iron supplementation during periods of life with physiologically increased cell proliferation. Levels of iron stores to be regarded as adequate during infancy and pregnancy are still not well established. Recent data support the view that it is not justified to interfere with physiological adaptations developed through millions of years by sophisticated and precisely coordinated regulation of iron absorption, utilization and storage. Recent data suggest that the chelatable intracellular iron pool regulates the expression of proteins with central importance in cellular iron metabolism (TfR, ferritin, and erythroid 5-aminolevulinic synthetase) in a coordinately controlled way through an iron dependent cytosolic mRNA binding protein, the iron regulating factor (IRF). This factor is simultaneously a sensor and a regulator of iron levels. The reduction of ferritin levels during highly increased cell proliferation is a mirror of the increased density of TfRs. An abundance of data support the vigorous competition for growth-essential iron between microbial pathogens and their vertebrate hosts. The highly coordinated regulation of iron metabolism is probably crucial in achieving a balance between the blockade of readily accessible iron to invading organisms and yet providing sufficient iron for the immune system of the host. The most evident adverse clinical effects of excess iron have been observed in immunodeficient patients in tropical countries and in AIDS patients. Excess iron also increases the risk of initiation and promotion of malignant processes by iron binding to DNA and by the iron-catalysed release of free radicals. Oxygen radicals were shown to damage critical biomolecules leading, apart from cancer, to a variety of human disease states, including inflammation and atherosclerosis. They are also involved in processes of aging and thrombosis. Recent clinical trials have suggested that the use of iron

  17. Natural history of ovarian cancer

    PubMed Central

    Vargas, Arturo Novoa

    2014-01-01

    Ovarian cancer is a disease laden with paradigms, and it is a serious health problem. It is important to know its natural history, as it is multifactorial in origin, and also to understand its behaviour given its risk factors which can lead to death from metastasis in patients. It continues to be a challenge for oncologists. An analytical literature review was performed to update the latest concepts of its origin, evolution, risk factors, pre-clinical horizon, and its clinical manifestations; until the death of the patient. PMID:25371706

  18. Natural history of ovarian cancer.

    PubMed

    Vargas, Arturo Novoa

    2014-01-01

    Ovarian cancer is a disease laden with paradigms, and it is a serious health problem. It is important to know its natural history, as it is multifactorial in origin, and also to understand its behaviour given its risk factors which can lead to death from metastasis in patients. It continues to be a challenge for oncologists. An analytical literature review was performed to update the latest concepts of its origin, evolution, risk factors, pre-clinical horizon, and its clinical manifestations; until the death of the patient.

  19. Efficacy and Safety of Pergoveris in Assisted Reproductive Technology—ESPART: rationale and design of a randomised controlled trial in poor ovarian responders undergoing IVF/ICSI treatment

    PubMed Central

    Humaidan, P; Schertz, J; Fischer, R

    2015-01-01

    Introduction The results of a recent meta-analysis showed that adding recombinant human luteinising hormone (r-hLH) to recombinant human follicle-stimulating hormone (r-hFSH) for ovarian stimulation was beneficial in poor responders, resulting in a 30% relative increase in the clinical pregnancy rate compared with r-hFSH monotherapy. However, a limitation of the meta-analysis was that the included studies used heterogeneous definitions of poor ovarian response (POR). Furthermore, the use of r-hLH supplementation during ovarian stimulation is a topic of ongoing debate, and well-designed, adequately powered, multicentre, randomised controlled trials in this setting are warranted. Therefore, the objective of the ESPART trial is to explore the possible superiority of a fixed-dose combination of r-hFSH plus r-hLH over r-hFSH monotherapy in patients with POR, as per a definition aligned with the European Society of Human Reproduction and Embryology (ESHRE) Bologna criteria. Methods and analysis Phase III, randomised, single-blind, parallel-group trial in women undergoing in vitro fertilisation and/or intracytoplasmic sperm injection. Approximately 946 women aged 18–<41 years from 18 countries will be randomised (1:1) to receive a fixed-dose combination of r-hFSH plus r-hLH in a 2:1 ratio (Pergoveris) or r-hFSH monotherapy (GONAL-f). The primary end point is the total number of retrieved oocytes per participant. Secondary end points include: ongoing pregnancy rate, live birth rate, implantation rate, biochemical pregnancy rate and clinical pregnancy rate. Safety end points include: incidence and severity of ovarian hyperstimulation syndrome, and of adverse events and serious adverse events. Ethics and dissemination The study will be performed in accordance with ethical principles that have their origin in the Declaration of Helsinki, with the International Conference on Harmonisation–Good Clinical Practice guidelines and all applicable regulatory requirements. All

  20. The Clinical Relevance of Beta Blockers in Ovarian Carcinoma

    PubMed Central

    Hefner, J.; Csef, H.

    2016-01-01

    The last ten years have seen hardly any improvement in the prognosis of ovarian carcinoma. There is a great need for new treatment strategies, and a recent retrospective study showing a survival advantage with the use of beta blockers met with a very positive response. This systematic review summarizes the current state of knowledge and research on the topic: A database analysis identified six clinical studies showing inconsistent results with respect to the administration of beta blockers and disease course. The 13 preclinical studies identified showed almost without exception both that catecholamines had detrimental effects on tumour progression, and that these effects could be influenced by pharmacological blockade. Overall the available evidence does not justify the use of beta blockers in clinical practice for ovarian carcinoma at the present time. This article also outlines details of research design required for further studies needed on the subject. Preclinical research findings are however very impressive: They not only form an important basis for the development of future clinical studies but also, through revealing new pathomechanisms, they already make an important contribution towards the development of new treatment strategies for ovarian carcinoma. PMID:27761025

  1. Perineal talc use and ovarian cancer: a critical review.

    PubMed

    Muscat, Joshua E; Huncharek, Michael S

    2008-04-01

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

  2. 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

  3. Smoke alarm tests may not adequately indicate smoke alarm function.

    PubMed

    Peek-Asa, Corinne; Yang, Jingzhen; Hamann, Cara; Young, Tracy

    2011-01-01

    Smoke alarms are one of the most promoted prevention strategies to reduce residential fire deaths, and they can reduce residential fire deaths by half. Smoke alarm function can be measured by two tests: the smoke alarm button test and the chemical smoke test. Using results from a randomized trial of smoke alarms, we compared smoke alarm response to the button test and the smoke test. The smoke alarms found in the study homes at baseline were tested, as well as study alarms placed into homes as part of the randomized trial. Study alarms were tested at 12 and 42 months postinstallation. The proportion of alarms that passed the button test but not the smoke test ranged from 0.5 to 5.8% of alarms; this result was found most frequently among ionization alarms with zinc or alkaline batteries. These alarms would indicate to the owner (through the button test) that the smoke alarm was working, but the alarm would not actually respond in the case of a fire (as demonstrated by failing the smoke test). The proportion of alarms that passed the smoke test but not the button test ranged from 1.0 to 3.0%. These alarms would appear nonfunctional to the owner (because the button test failed), even though the alarm would operate in response to a fire (as demonstrated by passing the smoke test). The general public is not aware of the potential for inaccuracy in smoke alarm tests, and burn professionals can advocate for enhanced testing methods. The optimal test to determine smoke alarm function is the chemical smoke test. PMID:21747329

  4. Biologic and immunologic therapy of ovarian cancer.

    PubMed

    Bookman, M A; Berek, J S

    1992-08-01

    Conventional cytotoxic chemotherapy fails to cure the majority of patients with advanced-stage ovarian cancer, in spite of encouraging initial antitumor responses. With the emergence of drug resistance in refractory tumors, new biologic and immunologic treatment strategies are needed. Small-volume residual peritoneal disease remains an attractive target for therapeutic trials; however, even in this optimal circumstance, few regimens have yet achieved a high frequency of pathologically confirmed complete remissions. Considerable progress has been made in understanding the impact of growth factors and their receptors on tumor growth regulation and modulation of response to chemotherapy. Better characterization of the antigens recognized by monoclonal antibodies, as well as sequencing of the antibodies themselves, has permitted the rational design of therapeutic reagents that take full advantage of molecular biology techniques for production and conjugation. Important limitations of preclinical models for prediction of host toxicity are recognized, and the reasons for treatment failure in situ, as well as strategies to prevent serious dose-limiting toxicities, are being explored. Further developments in cytokine biology, adoptive cellular therapy, monoclonal antibody conjugation, and molecular biology will continue to provide a growing array of reagents for critical evaluation.

  5. Thrombosis following ovarian hyperstimulation syndrome.

    PubMed

    Kasum, Miro; Danolić, Damir; Orešković, Slavko; Ježek, Davor; Beketić-Orešković, Lidija; Pekez, Marijeta

    2014-11-01

    The aim of this review is to analyse the pathophysiology and complications of thrombosis in conjuction with ovarian hyperstimulation syndrome (OHSS) following ovulation induction and to suggest practical guidelines usefull for the prevention and treatment. Although the incidence of thrombosis varies from 0.2% among in vitro fertilization (IVF) cycles and up to 10% for severe cases of the syndrome, it represents the most dangerous complication of OHSS. Different changes in haemostatic markers have been found to create a state of hypercoagulability, but no single standard test is available to estimate the state of thrombosis. The role of markers for thrombophilia is controversial. Thromboses are mostly venous (67-75%) involving upper limbs and neck, then arterial (25-33%) which are mainly intracerebral. The predominant sites of venous thromboembolism in the upper part of the body may be explained by higher concentrations of estrogens drained through lymphatic ducts from ascites and by compression of rudimentary branchyal cysts. Once early diagnosis is established, it is crucial to use an anticoagulant treatment with heparin proceeded with thromboprophylaxis. However, identification of patients at risk and preventive measures of OHSS are the best means in reducing the risk of thrombosis after ovarian stimulation.

  6. Update on Primary Ovarian Insufficiency

    PubMed Central

    Hewlett, Meghan; Mahalingaiah, Shruthi

    2016-01-01

    Purpose of Review Despite an incidence of one percent among women under the age of forty, primary ovarian insufficiency (POI) is still poorly understood. As the variable etiology and presentation of POI complicate its management, a standard regimen for treatment remains to be established. However, emerging research has provided new insight on current mainstays of treatment as well as novel management approaches and therapeutic interventions. Recent findings Recent clinical trials in women with POI indicate that the widely-used regimen of transdermal estradiol and medroxyprogesterone acetate restores bone mineral density (BMD) to a level equal to women with normal ovarian function. Further research verifies that compounded bioidentical hormones and androgen supplementation are inadequate in treating POI and lowering risk for long-term sequelae. Additionally, assessing changes in bone turnover markers may be useful for monitoring BMD. Alternative therapies such as acupuncture, DHEA, and buproprion may be effective in treating the effects of estrogen deficiency at some level, but require further investigation. Summary Recent updates show promise in improving management methods and reducing risk of long-term sequelae. Additional research that expands upon the most current literature is critical in order to achieve an evidence-based standard of best practice. PMID:26512773

  7. An Immunohistochemical Algorithm for Ovarian Carcinoma Typing

    PubMed Central

    Rahimi, Kurosh; Rambau, Peter F.; Naugler, Christopher; Le Page, Cécile; Meunier, Liliane; de Ladurantaye, Manon; Lee, Sandra; Leung, Samuel; Goode, Ellen L.; Ramus, Susan J.; Carlson, Joseph W.; Li, Xiaodong; Ewanowich, Carol A.; Kelemen, Linda E.; Vanderhyden, Barbara; Provencher, Diane; Huntsman, David; Lee, Cheng-Han; Gilks, C. Blake; Mes Masson, Anne-Marie

    2016-01-01

    There are 5 major histotypes of ovarian carcinomas. Diagnostic typing criteria have evolved over time, and past cohorts may be misclassified by current standards. Our objective was to reclassify the recently assembled Canadian Ovarian Experimental Unified Resource and the Alberta Ovarian Tumor Type cohorts using immunohistochemical (IHC) biomarkers and to develop an IHC algorithm for ovarian carcinoma histotyping. A total of 1626 ovarian carcinoma samples from the Canadian Ovarian Experimental Unified Resource and the Alberta Ovarian Tumor Type were subjected to a reclassification by comparing the original with the predicted histotype. Histotype prediction was derived from a nominal logistic regression modeling using a previously reclassified cohort (N=784) with the binary input of 8 IHC markers. Cases with discordant original or predicted histotypes were subjected to arbitration. After reclassification, 1762 cases from all cohorts were subjected to prediction models (χ2 Automatic Interaction Detection, recursive partitioning, and nominal logistic regression) with a variable IHC marker input. The histologic type was confirmed in 1521/1626 (93.5%) cases of the Canadian Ovarian Experimental Unified Resource and the Alberta Ovarian Tumor Type cohorts. The highest misclassification occurred in the endometrioid type, where most of the changes involved reclassification from endometrioid to high-grade serous carcinoma, which was additionally supported by mutational data and outcome. Using the reclassified histotype as the endpoint, a 4-marker prediction model correctly classified 88%, a 6-marker 91%, and an 8-marker 93% of the 1762 cases. This study provides statistically validated, inexpensive IHC algorithms, which have versatile applications in research, clinical practice, and clinical trials. PMID:26974996

  8. FSH-FSHR3-stem cells in ovary surface epithelium: basis for adult ovarian biology, failure, aging, and cancer.

    PubMed

    Bhartiya, Deepa; Singh, Jarnail

    2015-01-01

    Despite extensive research, genetic basis of premature ovarian failure (POF) and ovarian cancer still remains elusive. It is indeed paradoxical that scientists searched for mutations in FSH receptor (FSHR) expressed on granulosa cells, whereas more than 90% of cancers arise in ovary surface epithelium (OSE). Two distinct populations of stem cells including very small embryonic-like stem cells (VSELs) and ovarian stem cells (OSCs) exist in OSE, are responsible for neo-oogenesis and primordial follicle assembly in adult life, and are modulated by FSH via its alternatively spliced receptor variant FSHR3 (growth factor type 1 receptor acting via calcium signaling and the ERK/MAPK pathway). Any defect in FSH-FSHR3-stem cell interaction in OSE may affect folliculogenesis and thus result in POF. Ovarian aging is associated with a compromised microenvironment that does not support stem cell differentiation into oocytes and further folliculogenesis. FSH exerts a mitogenic effect on OSE and elevated FSH levels associated with advanced age may provide a continuous trigger for stem cells to proliferate resulting in cancer, thus supporting gonadotropin theory for ovarian cancer. Present review is an attempt to put adult ovarian biology, POF, aging, and cancer in the perspective of FSH-FSHR3-stem cell network that functions in OSE. This hypothesis is further supported by the recent understanding that: i) cancer is a stem cell disease and OSE is the niche for ovarian cancer stem cells; ii) ovarian OCT4-positive stem cells are regulated by FSH; and iii) OCT4 along with LIN28 and BMP4 are highly expressed in ovarian cancers.

  9. Relationships between milk production, ovarian function and fertility in high-producing dairy herds in north-eastern Spain.

    PubMed

    Yániz, J; López-Gatius, F; Bech-Sàbat, G; García-Ispierto, I; Serrano, B; Santolaria, P

    2008-10-01

    In the dairy industry worldwide, reproductive disorders are a major cause of economic losses and a challenge to scientists and technicians. In recent decades, declining fertility and increasing milk production have been widely reported in dairy cattle. In this article, the relationships between milk production, ovarian disorders and fertility in high-producing dairy herds are briefly described. We carried out a retrospective study of 23 204 lactations included in a reproductive control programme in north-eastern Spain, a geographical area experiencing both warm and cool conditions. The data were collected between 1991 and 2007 and refer to cows first inseminated or examined 45-80 days postpartum in five well-managed, commercial, Holstein-Friesian high-producing dairy herds. Ovarian disorders were classified as ovarian inactivity or hypofunction, cystic ovarian disease, sub-oestrus or silent ovulation and sub-luteal function. Ovarian hypofunction and milk production increased throughout the study period and there was a decrease in the pregnancy rate to first artificial insemination (AI). Cows suffering ovarian hypofunction were efficiently treated using combined progestagen-prostaglandin treatments. The incidence of ovarian cysts showed little variation with time. Treatment of this syndrome may include different GnRH-based treatments or manual rupture. During the last 5 years, sub-oestrus was the predominant dysfunction (42.1%) compared with the cystic (6.3%) and ovarian hypofunction (12%) forms. Response of sub-oestrous cows to treatment with luteolitic agents was usually higher than 60%. Ovarian function and fertility were dramatically impaired during the warm period. However, during the later years of the study, the inclusion of fans and water sprinklers for the warm season appeared to overcome the seasonal effect on fertility. PMID:18803755

  10. Achieving adequate BMP`s for stormwater quality management

    SciTech Connect

    Jones-Lee, A.; Lee, G.F.

    1994-12-31

    There is considerable controversy about the technical appropriateness and the cost-effectiveness of requiring cities to control contaminants in urban stormwater discharges to meet state water quality standards equivalent to US EPA numeric chemical water quality criteria. At this time and likely for the next 10 years, urban stormwater discharges will be exempt from regulation to achieve state water quality standards in receiving waters, owing to the high cost to cities of the management of contaminants in the stormwater runoff-discharge so as to prevent exceedances of water quality standards in the receiving waters. Instead of requiring the same degree of contaminant control for stormwater discharges as is required for point-source discharges of municipal and industrial wastewaters, those responsible for urban stormwater discharges will have to implement Best Management Practices (BMP`s) for contaminant control. The recommended approach for implementation of BMP`s involves the use of site-specific evaluations of what, if any, real problems (use impairment) are caused by stormwater-associated contaminants in the waters receiving that stormwater discharge. From this type of information BMP`s can then be developed to control those contaminants in stormwater discharges that are, in fact, impairing the beneficial uses of receiving waters.

  11. Bronchoalveolar Lavage (BAL) for Research; Obtaining Adequate Sample Yield

    PubMed Central

    Collins, Andrea M.; Rylance, Jamie; Wootton, Daniel G.; Wright, Angela D.; Wright, Adam K. A.; Fullerton, Duncan G.; Gordon, Stephen B.

    2014-01-01

    We describe a research technique for fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) using manual hand held suction in order to remove nonadherent cells and lung lining fluid from the mucosal surface. In research environments, BAL allows sampling of innate (lung macrophage), cellular (B- and T- cells), and humoral (immunoglobulin) responses within the lung. BAL is internationally accepted for research purposes and since 1999 the technique has been performed in > 1,000 subjects in the UK and Malawi by our group. Our technique uses gentle hand-held suction of instilled fluid; this is designed to maximize BAL volume returned and apply minimum shear force on ciliated epithelia in order to preserve the structure and function of cells within the BAL fluid and to preserve viability to facilitate the growth of cells in ex vivo culture. The research technique therefore uses a larger volume instillate (typically in the order of 200 ml) and employs manual suction to reduce cell damage. Patients are given local anesthetic, offered conscious sedation (midazolam), and tolerate the procedure well with minimal side effects. Verbal and written subject information improves tolerance and written informed consent is mandatory. Safety of the subject is paramount. Subjects are carefully selected using clear inclusion and exclusion criteria. This protocol includes a description of the potential risks, and the steps taken to mitigate them, a list of contraindications, pre- and post-procedure checks, as well as precise bronchoscopy and laboratory techniques. PMID:24686157

  12. Are family medicine residents adequately trained to deliver palliative care?

    PubMed Central

    Mahtani, Ramona; Kurahashi, Allison M.; Buchman, Sandy; Webster, Fiona; Husain, Amna; Goldman, Russell

    2015-01-01

    Objective To explore educational factors that influence family medicine residents’ (FMRs’) intentions to offer palliative care and palliative care home visits to patients. Design Qualitative descriptive study. Setting A Canadian, urban, specialized palliative care centre. Participants First-year (n = 9) and second-year (n = 6) FMRs. Methods Semistructured interviews were conducted with FMRs following a 4-week palliative care rotation. Questions focused on participant experiences during the rotation and perceptions about their roles as family physicians in the delivery of palliative care and home visits. Participant responses were analyzed to summarize and interpret patterns related to their educational experience during their rotation. Main findings Four interrelated themes were identified that described this experience: foundational skill development owing to training in a specialized setting; additional need for education and support; unaddressed gaps in pragmatic skills; and uncertainty about family physicians’ role in palliative care. Conclusion Residents described experiences that both supported and inadvertently discouraged them from considering future engagement in palliative care. Reassuringly, residents were also able to underscore opportunities for improvement in palliative care education. PMID:27035008

  13. Bronchoalveolar lavage (BAL) for research; obtaining adequate sample yield.

    PubMed

    Collins, Andrea M; Rylance, Jamie; Wootton, Daniel G; Wright, Angela D; Wright, Adam K A; Fullerton, Duncan G; Gordon, Stephen B

    2014-01-01

    We describe a research technique for fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) using manual hand held suction in order to remove nonadherent cells and lung lining fluid from the mucosal surface. In research environments, BAL allows sampling of innate (lung macrophage), cellular (B- and T- cells), and humoral (immunoglobulin) responses within the lung. BAL is internationally accepted for research purposes and since 1999 the technique has been performed in > 1,000 subjects in the UK and Malawi by our group. Our technique uses gentle hand-held suction of instilled fluid; this is designed to maximize BAL volume returned and apply minimum shear force on ciliated epithelia in order to preserve the structure and function of cells within the BAL fluid and to preserve viability to facilitate the growth of cells in ex vivo culture. The research technique therefore uses a larger volume instillate (typically in the order of 200 ml) and employs manual suction to reduce cell damage. Patients are given local anesthetic, offered conscious sedation (midazolam), and tolerate the procedure well with minimal side effects. Verbal and written subject information improves tolerance and written informed consent is mandatory. Safety of the subject is paramount. Subjects are carefully selected using clear inclusion and exclusion criteria. This protocol includes a description of the potential risks, and the steps taken to mitigate them, a list of contraindications, pre- and post-procedure checks, as well as precise bronchoscopy and laboratory techniques.

  14. Prevention of chemotherapy-induced ovarian damage.

    PubMed

    Roness, Hadassa; Kashi, Oren; Meirow, Dror

    2016-01-01

    Recent advances in our understanding of the mechanisms underlying the impact of cytotoxic drugs on the ovary have opened up new directions for the protection of the ovary from chemotherapy-induced damage. These advances have spurred the investigation of pharmacological agents to prevent ovarian damage at the time of treatment. Prevention of ovarian damage and follicle loss would provide significant advantages over existing fertility preservation techniques. This manuscript reviews new methods for the prevention of chemotherapy-induced ovarian damage, including agents that act on the PI3K/PTEN/Akt follicle activation pathway, apoptotic pathways, the vascular system, and other potential methods of reducing chemotherapy-induced ovotoxicity.

  15. Ovarian cancer: emerging molecular-targeted therapies

    PubMed Central

    Sourbier, Carole

    2012-01-01

    With about 22,000 new cases estimated in 2012 in the US and 15,500 related deaths, ovarian cancer is a heterogeneous and aggressive disease. Even though most of patients are sensitive to chemotherapy treatment following surgery, recurring disease is almost always lethal, and only about 30% of the women affected will be cured. Thanks to a better understanding of the molecular mechanisms underlying ovarian cancer malignancy, new therapeutic options with molecular-targeted agents have become available. This review discusses the rationale behind molecular-targeted therapies and examines how newly identified molecular targets may enhance personalized therapies for ovarian cancer patients. PMID:22807625

  16. Ultrasound scanning of the ovarian cycle.

    PubMed

    Hackelöer, B J

    1984-12-01

    Ultrasound scanning of the ovarian cycle is a simple noninvasive technique for monitoring ovarian activity. It helps to predict a mature follicle and the time of ovulation more accurately than the basal body temperature and more rapidly and cheaply than a hormone profile, but still only one facet of ovarian activity. With respect to in vitro fertilization, egg collection can be undertaken by means of sonically guided puncture via the bladder, which is reported later in this issue. Replacement of the embryo can be controlled by sonar visualization of catheter. The use of ultrasound has proved to be extremely helpful in the management of the infertile couple.

  17. The flavonoid nobiletin inhibits tumor growth and angiogenesis of ovarian cancers via the Akt pathway.

    PubMed

    Chen, Jianchu; Chen, Allen Y; Huang, Haizhi; Ye, Xingqian; Rollyson, William D; Perry, Haley E; Brown, Kathleen C; Rojanasakul, Yon; Rankin, Gary O; Dasgupta, Piyali; Chen, Yi Charlie

    2015-01-01

    Despite its importance, the death rate of ovarian cancer has remained unchanged over the past five decades, demanding an improvement in prevention and treatment of this malignancy. With no known carcinogens, targeted prevention is currently unavailable, and efforts in early detection of this malignancy by screening biomarkers have failed. The inhibition of angiogenesis, also known as angioprevention, is a promising strategy to limit the growth of solid tumors, including ovarian cancers. Nobiletin, a polymethoxy flavonoid compound isolated from the tiansheng plant, has been shown to inhibit the growth of multiple types of human cancers. However, there are no reports involving the effect on nobiletin on human ovarian cancer. The present report shows that nobiletin potently decreases the viability of ovarian cancer cells in vitro. However, nobiletin does not affect the viability of normal ovarian epithelial cells at <40 µM. The antitumor activity of nobiletin was also observed in athymic mouse models and in chicken chorioallantoic membrane (CAM) models. The anti-neoplastic activity of nobiletin was due to its ability to inhibit angiogenesis. We also studied the molecular mechanisms by which nobiletin suppresses angiogenesis. We observed that nobiletin inhibits secretion of the key angiogenesis mediators, Akt, HIF-1α, NF-κB and vascular epithelial growth factor (VEGF) by ovarian cancer cells. Transient transfection experiments showed that nobiletin inhibits production of HIF-1α by downregulation of Akt. Such decreased levels of HIF-1α were responsible for nobiletin-induced suppression of VEGF. Our data suggest that nobiletin may be a promising anti-angiogenic agent relevant for therapy of ovarian cancers.

  18. The flavonoid nobiletin inhibits tumor growth and angiogenesis of ovarian cancers via the Akt pathway.

    PubMed

    Chen, Jianchu; Chen, Allen Y; Huang, Haizhi; Ye, Xingqian; Rollyson, William D; Perry, Haley E; Brown, Kathleen C; Rojanasakul, Yon; Rankin, Gary O; Dasgupta, Piyali; Chen, Yi Charlie

    2015-01-01

    Despite its importance, the death rate of ovarian cancer has remained unchanged over the past five decades, demanding an improvement in prevention and treatment of this malignancy. With no known carcinogens, targeted prevention is currently unavailable, and efforts in early detection of this malignancy by screening biomarkers have failed. The inhibition of angiogenesis, also known as angioprevention, is a promising strategy to limit the growth of solid tumors, including ovarian cancers. Nobiletin, a polymethoxy flavonoid compound isolated from the tiansheng plant, has been shown to inhibit the growth of multiple types of human cancers. However, there are no reports involving the effect on nobiletin on human ovarian cancer. The present report shows that nobiletin potently decreases the viability of ovarian cancer cells in vitro. However, nobiletin does not affect the viability of normal ovarian epithelial cells at <40 µM. The antitumor activity of nobiletin was also observed in athymic mouse models and in chicken chorioallantoic membrane (CAM) models. The anti-neoplastic activity of nobiletin was due to its ability to inhibit angiogenesis. We also studied the molecular mechanisms by which nobiletin suppresses angiogenesis. We observed that nobiletin inhibits secretion of the key angiogenesis mediators, Akt, HIF-1α, NF-κB and vascular epithelial growth factor (VEGF) by ovarian cancer cells. Transient transfection experiments showed that nobiletin inhibits production of HIF-1α by downregulation of Akt. Such decreased levels of HIF-1α were responsible for nobiletin-induced suppression of VEGF. Our data suggest that nobiletin may be a promising anti-angiogenic agent relevant for therapy of ovarian cancers. PMID:25845666

  19. Ovarian hormone status and skeletal muscle inflammation during recovery from disuse in rats.

    PubMed

    McClung, J M; Davis, J M; Carson, J A

    2007-01-01

    Resumption of normal muscle loading after a period of disuse initiates cellular processes related to mass accretion. The renewed loading also induces a significant amount of muscle damage and subsequent inflammation. Ovarian hormone depletion delays atrophied myofibre mass recovery. Ovarian hormones are also global regulators of immune system function. The purpose of this study was to determine whether ovarian hormone depletion-induced deficits in myofibre regrowth after disuse atrophy are related to the induction of muscle damage and the associated inflammatory response. We hypothesized that soleus muscle immune cell infiltration and inflammatory gene expression would be both accentuated and prolonged in ovarian hormone-depleted rats during the first week of recovery from disuse atrophy. Intact and ovariectomized (OVX) female rats were subjected to hindlimb suspension for 10 days and then returned to normal ambulation for a recovery period, the rats were killed and the soleus muscle removed for analysis. Although reloading increased both circulating creatine kinase and myofibre membrane disruption, there was no effect of ovarian hormones on these processes during recovery. Muscle neutrophil concentration was increased above baseline regardless of hormone status at days 1 and 3 of recovery; however, this increase was 43% greater at day 3 in the OVX group. Muscle ED1+ and ED2+ macrophage concentrations were increased during recovery in both groups. However, macropage concentrations remained elevated at day 7 of recovery in the OVX group, whereas they returned to control levels in the intact group. Cyclo-oxygenase-2, interleukin-6 and interleukin-1beta muscle mRNA expression increased similarly during recovery, regardless of ovarian hormone status. These results demonstrate that the initial myofibre damage and inflammatory gene expression induced during muscle recovery from disuse atrophy are independent of ovarian hormone status.

  20. The TP73 Gene Polymorphism (rs4648551, A>G) Is Associated with Diminished Ovarian Reserve

    PubMed Central

    Vagnini, Laura Diniz; Renzi, Adriana; Oliveira-Pelegrin, Gabriela Ravanelli; Canas, Maria do Carmo Tomitão; Petersen, Claudia Guilhermino; Mauri, Ana Lucia; Oliveira, João Batista Alcantara; Baruffi, Ricardo Luiz Razera; Cavagna, Mario; Franco Junior, José Gonçalves

    2015-01-01

    It’s known that the members of the TP53 family are involved in the regulation of female reproduction. Studies in mice showed that the TP73 gene (member of this family) plays a role in the size of follicular pool, ovulation rate and maintenance of genomic stability. In the present study we analyzed data from 605 patients with ≤ 37 years attending their first intracytoplasmic sperm injection (ICSI). The association between the TP73 polymorphism (rs4648551, A>G) and the following parameters related to ovarian reserve, like age, antral follicular count (AFC), anti-Mullerian hormone levels (AMH) and ovarian response prediction index (ORPI) was evaluated. Our results showed an association of the AA genotype with diminished ovarian reserve (AMH <1, AFC ≤9). Women presenting the AA genotype had a 2.0-fold increased risk for having AMH <1 and AFC ≤9 (OR 2.0, 95% CI 1.23-3.31, P = 0.005). Patients presenting AA genotype had the lowest levels of AMH (P = 0.02), the lowest number of antral follicles (P = 0.01) and the lowest ORPI (P = 0.007). Analyzing the alleles, we can see an enrichment of the A allele in the group of diminished ovarian reserve (OR 1.4, 95%CI 1.02-1.83, P = 0.04). To the best of our knowledge, the present study is the first to analyze this polymorphism in humans for assessing the numbers of ovarian follicles and AMH levels and, therefore, the ovarian reserve. Our findings can contribute to the use of this polymorphism as a potential marker of diminished ovarian reserve. PMID:25794170

  1. Changes in Brain Function in Patients With Stage I, Stage II, Stage III, or Stage IV Ovarian, Primary Peritoneal, or Fallopian Tube Cancer Who Are Receiving Chemotherapy

    ClinicalTrials.gov

    2016-10-26

    Cognitive Side Effects of Cancer Therapy; Malignant Ovarian Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Carcinosarcoma; Ovarian Choriocarcinoma; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Dysgerminoma; Ovarian Embryonal Carcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Germ Cell Tumor; Ovarian Mucinous Cystadenocarcinoma; Ovarian Polyembryoma; Ovarian Sarcoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Teratoma; Ovarian Yolk Sac Tumor; Stage I Ovarian Cancer; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Cancer; Stage IA Ovarian Germ Cell Tumor; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Cancer; Stage IB Ovarian Germ Cell Tumor; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Cancer; Stage IC Ovarian Germ Cell Tumor; Stage II Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIA Ovarian Germ Cell Tumor; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIB Ovarian Germ Cell Tumor; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIC Ovarian Germ Cell Tumor; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Primary Peritoneal Cancer; Undifferentiated Ovarian Carcinoma

  2. Ovarian cyst aspiration prior to initiating ovarian hyperstimulation for in vitro fertilization.

    PubMed

    Silverberg, K M; Olive, D L; Schenken, R S

    1990-06-01

    Twenty-three consecutive patients presenting for in vitro fertilization were evaluated with transvaginal sonography on cycle day 3, prior to initiating ovarian hyperstimulation. Three of these patients were noted to have large ovarian cysts. All three underwent transvaginal aspiration of the cysts, followed immediately by initiation of ovarian hyperstimulation. Following oocyte retrieval, in vitro fertilization, and embryo transfer, all three women achieved pregnancy. We conclude that cyst aspiration is not contraindicated when an ovarian cyst is encountered in the follicular phase of an in vitro fertilization cycle.

  3. PAX2 Expression in Low Malignant Potential Ovarian Tumors and Low-Grade Ovarian Serous Carcinomas

    PubMed Central

    Tung, Celestine S.; Mok, Samuel C.; Tsang, Yvonne T.M.; Zu, Zhifei; Song, Huijuan; Liu, Jinsong; Deavers, Michael; Malpica, Anais; Wolf, Judith K.; Lu, Karen H.; Gershenson, David M.; Wong, Kwong-Kwok

    2009-01-01

    Ovarian tumors of low-malignant potential and low-grade ovarian serous carcinomas are thought to represent different stages on a tumorigenic continuum and to develop along pathways distinct from high-grade ovarian serous carcinoma. We performed gene expression profiling on 3 normal human ovarian surface epithelia samples, and 10 low-grade and 10 high-grade ovarian serous carcinomas. Analysis of gene expression profiles of these samples has identified 80 genes up-regulated and 232 genes down-regulated in low-grade ovarian serous carcinomas. PAX2 was found to be one of the most up-regulated genes in low-grade ovarian serous carcinoma. The up-regulation of PAX2 was validated by real-time quantitative RT-PCR, Western blot and immunohistochemical analyses. Real-time RT-PCR demonstrated a statistically significant difference in PAX2 mRNA expression (expressed as fold change in comparison to normal human ovarian surface epithelia) among ovarian tumors of low-malignant potential (1837.38, N=8), low-grade (183.12, N=17), and high-grade (3.72, N=23) carcinoma samples (p=0.015). Western blot analysis revealed strong PAX2 expression in ovarian tumors of low-malignant potential (67%, N=3) and low-grade carcinoma samples (50%, N=10) but no PAX2 protein expression in high-grade carcinomas (0%, N=10). Using immunohistochemistry, tumors of low-malignant potential (59%, N=17) and low-grade carcinoma (63%, N=16) samples expressed significantly stronger nuclear staining than high-grade ovarian carcinoma samples (9.1%, N=263). Furthermore, consistent with previous immunohistochemical findings, PAX2 expression was found to be expressed in the epithelial cells of fallopian tubes but not in normal ovarian surface epithelial cells. Our findings further support the two-tiered hypothesis that tumors of low-malignant potential and low-grade ovarian serous carcinoma are on a continuum and are distinct from high-grade ovarian carcinomas. Additionally, the absence of PAX2 expression in normal

  4. Which kind of psychometrics is adequate for patient satisfaction questionnaires?

    PubMed Central

    Konerding, Uwe

    2016-01-01

    The construction and psychometric analysis of patient satisfaction questionnaires are discussed. The discussion is based upon the classification of multi-item questionnaires into scales or indices. Scales consist of items that describe the effects of the latent psychological variable to be measured, and indices consist of items that describe the causes of this variable. Whether patient satisfaction questionnaires should be constructed and analyzed as scales or as indices depends upon the purpose for which these questionnaires are required. If the final aim is improving care with regard to patients’ preferences, then these questionnaires should be constructed and analyzed as indices. This implies two requirements: 1) items for patient satisfaction questionnaires should be selected in such a way that the universe of possible causes of patient satisfaction is covered optimally and 2) Cronbach’s alpha, principal component analysis, exploratory factor analysis, confirmatory factor analysis, and analyses with models from item response theory, such as the Rasch Model, should not be applied for psychometric analyses. Instead, multivariate regression analyses with a direct rating of patient satisfaction as the dependent variable and the individual questionnaire items as independent variables should be performed. The coefficients produced by such an analysis can be applied for selecting the best items and for weighting the selected items when a sum score is determined. The lower boundaries of the validity of the unweighted and the weighted sum scores can be estimated by their correlations with the direct satisfaction rating. While the first requirement is fulfilled in the majority of the previous patient satisfaction questionnaires, the second one deviates from previous practice. Hence, if patient satisfaction is actually measured with the final aim of improving care with regard to patients’ preferences, then future practice should be changed so that the second

  5. Percentage of Adults with High Blood Pressure Whose Hypertension Is Adequately Controlled

    MedlinePlus

    ... is Adequately Controlled Percentage of Adults with High Blood Pressure Whose Hypertension is Adequately Controlled Heart disease ... Survey. Age Group Percentage of People with High Blood Pressure that is Controlled by Age Group f94q- ...

  6. Ovarian strumal carcinoid producing peptide YY associated with severe constipation: a case report and review of the literature.

    PubMed

    Muller, Kristen E; Tafe, Laura J; Gonzalez, Jorge L; West, Loyd A; Schned, Alan R

    2015-01-01

    Primary carcinoid tumors are rare neoplasms of the ovary. Of the 4 histologic subtypes, ovarian carcinoid tumors with insular patterns produce carcinoid syndrome in approximately one third of cases, versus strumal and trabecular carcinoids which very rarely cause typical carcinoid syndrome. A unique presentation of ovarian carcinoid tumors with concurrent severe constipation has been reported, which is thought to represent a new carcinoid syndrome. The proposed mechanism is the production of peptide YY by the tumor, a gastrointestinal hormone responsible for decreasing gut motility. We report a case of a 34-yr-old white woman who presented with constipation and weight loss for 1 yr, and was found to have a unilateral ovarian strumal carcinoid, which produced peptide YY as demonstrated by immunohistochemistry. The 13 previous case reports of ovarian carcinoids with constipation are reviewed and the clinicopathologic features are discussed. This report and literature review further solidifies this entity as a new type of carcinoid syndrome.

  7. 76 FR 51041 - Hemoglobin Standards and Maintaining Adequate Iron Stores in Blood Donors; Public Workshop

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-17

    ... HUMAN SERVICES Food and Drug Administration Hemoglobin Standards and Maintaining Adequate Iron Stores in... Standards and Maintaining Adequate Iron Stores in Blood Donors.'' The purpose of this public workshop is to... donor safety and blood availability, and potential measures to maintain adequate iron stores in...

  8. 21 CFR 801.5 - Medical devices; adequate directions for use.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Medical devices; adequate directions for use. 801... (CONTINUED) MEDICAL DEVICES LABELING General Labeling Provisions § 801.5 Medical devices; adequate directions for use. Adequate directions for use means directions under which the layman can use a device...

  9. 36 CFR 13.960 - Who determines when there is adequate snow cover?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... adequate snow cover? 13.960 Section 13.960 Parks, Forests, and Public Property NATIONAL PARK SERVICE... Preserve Snowmachine (snowmobile) Operations § 13.960 Who determines when there is adequate snow cover? The superintendent will determine when snow cover is adequate for snowmachine use. The superintendent will follow...

  10. 36 CFR 13.960 - Who determines when there is adequate snow cover?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... adequate snow cover? 13.960 Section 13.960 Parks, Forests, and Public Property NATIONAL PARK SERVICE... Preserve Snowmachine (snowmobile) Operations § 13.960 Who determines when there is adequate snow cover? The superintendent will determine when snow cover is adequate for snowmachine use. The superintendent will follow...

  11. 36 CFR 13.960 - Who determines when there is adequate snow cover?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... adequate snow cover? 13.960 Section 13.960 Parks, Forests, and Public Property NATIONAL PARK SERVICE... Preserve Snowmachine (snowmobile) Operations § 13.960 Who determines when there is adequate snow cover? The superintendent will determine when snow cover is adequate for snowmachine use. The superintendent will follow...

  12. 36 CFR 13.960 - Who determines when there is adequate snow cover?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... adequate snow cover? 13.960 Section 13.960 Parks, Forests, and Public Property NATIONAL PARK SERVICE... Preserve Snowmachine (snowmobile) Operations § 13.960 Who determines when there is adequate snow cover? The superintendent will determine when snow cover is adequate for snowmachine use. The superintendent will follow...

  13. [Epidemiology of presumed benign ovarian tumors].

    PubMed

    Mimoun, C; Fritel, X; Fauconnier, A; Deffieux, X; Dumont, A; Huchon, C

    2013-12-01

    Ovarian cysts presumed benign can be organic or functional. Their prevalence is estimated between 14 and 18% in postmenopausal women and around 7% in asymptomatic women of childbearing age. Their incidence during pregnancy is between 0.2 and 5% and varies within the term of pregnancy. Ovarian cysts presumed benign have caused nearly 45,000 hospitalizations in France in 2012, bringing the annual risk of hospitalization for a woman residing in France to 1.3‰. Among the risk factors studied in the literature, tamoxifen increases the incidence of ovarian cysts in premenopausal patients and immunosuppressive treatments are associated with a high prevalence of benign ovarian cysts while estrogen contraception reduces the risk of developing functional cysts.

  14. General Information about Ovarian Epithelial Cancer

    MedlinePlus

    ... Primary Peritoneal Cancer Treatment (PDQ®)–Patient Version General Information About Ovarian Epithelial, Fallopian Tube, and Primary Peritoneal ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  15. General Information about Ovarian Germ Cell Tumors

    MedlinePlus

    ... Germ Cell Tumors Treatment (PDQ®)–Patient Version General Information About Ovarian Germ Cell Tumors Go to Health ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  16. Genetic and molecular changes in ovarian cancer

    PubMed Central

    Hollis, Robert L; Gourley, Charlie

    2016-01-01

    Epithelial ovarian cancer represents the most lethal gynecological malignancy in the developed world, and can be divided into five main histological subtypes: high grade serous, endometrioid, clear cell, mucinous and low grade serous. These subtypes represent distinct disease entities, both clinically and at the molecular level. Molecular analysis has revealed significant genetic heterogeneity in ovarian cancer, particularly within the high grade serous subtype. As such, this subtype has been the focus of much research effort to date, revealing molecular subgroups at both the genomic and transcriptomic level that have clinical implications. However, stratification of ovarian cancer patients based on the underlying biology of their disease remains in its infancy. Here, we summarize the molecular changes that characterize the five main ovarian cancer subtypes, highlight potential opportunities for targeted therapeutic intervention and outline priorities for future research. PMID:27458531

  17. Novel Treatment Shrinks Ovarian Tumors in Mice

    Cancer.gov

    Researchers have developed a new approach for treating tumors that express mutant versions of the p53 protein, which are present in more than half of all cancers, including an aggressive and common subtype of ovarian cancer.

  18. Live birth after ovarian tissue transplant

    NASA Astrophysics Data System (ADS)

    Lee, D. M.; Yeoman, R. R.; Battaglia, D. E.; Stouffer, R. L.; Zelinski-Wooten, M. B.; Fanton, J. W.; Wolf, D. P.

    2004-03-01

    Radiation and high-dose chemotherapy may render women with cancer prematurely sterile, a side-effect that would be avoided if ovarian tissue that had been removed before treatment could be made to function afterwards. Live offspring have been produced from transplanted ovarian tissue in mice and sheep but not in monkeys or humans, although sex steroid hormones are still secreted. Here we describe the successful transplantation of fresh ovarian tissue to a different site in a monkey, which has led to the birth of a healthy female after oocyte production, fertilization and transfer to a surrogate mother. The ectopically grafted tissue functions without surgical connection to major blood vessels and sets the stage for the transplantation of cryopreserved ovarian tissue in humans.

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

    PubMed Central

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

    2001-01-01

    Ovarian cancer is the most frequent cause of death from gynaecological malignancies world wide. Little improvement has been made in the long-term outcome of this disease, with the 5-year survival of patients only 30%. This poor prognosis is due to the late presentation of the disease and to the unpredictable response of ovarian cancer to chemotherapy. The cytochrome P450 enzymes are a superfamily of haemoproteins, known to be involved in the metabolic activation and/or detoxification of a number of anti-cancer drugs. CYP1B1 is a tumour-related form of cytochrome P450 which is over expressed in a wide variety of primary tumours of different histological type. The presence of CYP1B1 may be of importance in the modulation of these tumours to anti-cancer drugs. We have conducted a comprehensive immunohistochemical investigation, into the presence of cytochrome P450 CYP1B1 in primary and metastatic ovarian cancer. The key findings of this study are the increased expression of CYP1B1 in the majority of ovarian cancers investigated (92%), with a strong correlation demonstrated between CYP1B1 expression in both primary and metastatic ovarian cancer (P= 0.005 Spearman's rank correlation test). In contrast no detectable CYP1B1 was found in normal ovary. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11461084

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

    PubMed

    Wang, Jianxia; Yuan, Zhixiang

    2013-09-01

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

  1. Anti-Mullerian Hormone: Above and Beyond Conventional Ovarian Reserve Markers

    PubMed Central

    Jamil, Zehra; Fatima, Syeda Sadia; Ahmed, Khalid; Malik, Rabia

    2016-01-01

    Management of ovarian dysfunctions requires accurate estimation of ovarian reserve (OR). Therefore, reproductive hormones and antral follicle count (AFC) are assessed to indicate OR. Serum anti-Mullerian hormone (AMH) is a unique biomarker that has a critical role in folliculogenesis as well as steroidogenesis within ovaries. Secretion from preantral and early antral follicles renders AMH as the earliest marker to show OR decline. In this review we discuss the dynamics of circulating AMH that remarkably vary with sex and age. As it emerges as a marker of gonadal development and reproductive disorders, here we summarize the role of AMH in female reproductive physiology and provide evidence of higher accuracy in predicting ovarian response to stimulation. Further, we attempt to compile potential clinical applications in children and adults. We propose that AMH evaluation has a potential role in effectively monitoring chemotherapy and pelvic radiation induced ovarian toxicity. Furthermore, AMH guided ovarian stimulation can lead to individualization of therapeutic strategies for infertility treatment. However future research on AMH levels within follicular fluid may pave the way to establish it as a marker of “quality” besides “quantity” of the growing follicles. PMID:26977116

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

    PubMed

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

    2012-05-01

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

  3. Evaluation of CD46 re-targeted adenoviral vectors for clinical ovarian cancer intraperitoneal therapy

    PubMed Central

    Hulin-Curtis, S L; Uusi-Kerttula, H; Jones, R; Hanna, L; Chester, J D; Parker, A L

    2016-01-01

    Ovarian cancer accounts for >140 000 deaths globally each year. Typically, disease is asymptomatic until an advanced, incurable stage. Although response to cytotoxic chemotherapy is frequently observed, resistance to conventional platinum-based therapies develop rapidly. Improved treatments are therefore urgently required. Virotherapy offers great potential for ovarian cancer, where the application of local, intraperitoneal delivery circumvents some of the limitations of intravenous strategies. To develop effective, adenovirus (Ad)-based platforms for ovarian cancer, we profiled the fluid and cellular components of patient ascites for factors known to influence adenoviral transduction. Levels of factor X (FX) and neutralizing antibodies (nAbs) in ascitic fluid were quantified and tumor cells were assessed for the expression of coxsackie virus and adenovirus receptor (CAR) and CD46. We show that clinical ascites contains significant levels of FX but consistently high CD46 expression. We therefore evaluated in vitro the relative transduction of epithelial ovarian cancers (EOCs) by Ad5 (via CAR) and Ad5 pseudotyped with the fiber of Ad35 (Ad5T*F35++) via CD46. Ad5T*F35++ achieved significantly increased transduction in comparison to Ad5 (P<0.001), independent of FX and nAb levels. We therefore propose selective transduction of CD46 over-expressing EOCs using re-targeted, Ad35-pseudotyped Ad vectors may represent a promising virotherapy for ovarian cancer. PMID:27229159

  4. Evaluation of CD46 re-targeted adenoviral vectors for clinical ovarian cancer intraperitoneal therapy.

    PubMed

    Hulin-Curtis, S L; Uusi-Kerttula, H; Jones, R; Hanna, L; Chester, J D; Parker, A L

    2016-07-01

    Ovarian cancer accounts for >140 000 deaths globally each year. Typically, disease is asymptomatic until an advanced, incurable stage. Although response to cytotoxic chemotherapy is frequently observed, resistance to conventional platinum-based therapies develop rapidly. Improved treatments are therefore urgently required. Virotherapy offers great potential for ovarian cancer, where the application of local, intraperitoneal delivery circumvents some of the limitations of intravenous strategies. To develop effective, adenovirus (Ad)-based platforms for ovarian cancer, we profiled the fluid and cellular components of patient ascites for factors known to influence adenoviral transduction. Levels of factor X (FX) and neutralizing antibodies (nAbs) in ascitic fluid were quantified and tumor cells were assessed for the expression of coxsackie virus and adenovirus receptor (CAR) and CD46. We show that clinical ascites contains significant levels of FX but consistently high CD46 expression. We therefore evaluated in vitro the relative transduction of epithelial ovarian cancers (EOCs) by Ad5 (via CAR) and Ad5 pseudotyped with the fiber of Ad35 (Ad5T*F35++) via CD46. Ad5T*F35++ achieved significantly increased transduction in comparison to Ad5 (P<0.001), independent of FX and nAb levels. We therefore propose selective transduction of CD46 over-expressing EOCs using re-targeted, Ad35-pseudotyped Ad vectors may represent a promising virotherapy for ovarian cancer.

  5. Minimal-change disease as a paraneoplastic syndrome in a patient with ovarian carcinoma.

    PubMed

    González-Fontal, Guido R; Restrepo, Juan G; Henao-Martínez, Andrés F

    2011-12-01

    Minimal-change disease (MCD) is an exceptional paraneoplastic presentation. We are describing the case of an ovarian paraneoplastic nephrotic syndrome. The kidney biopsy was consistent with MCD. Steroids and immunosuppressive therapy were given with no change in the nephrotic-range proteinuria. A complete resolution of the nephrotic syndrome was soon observed with improvement of her clinical condition after five cycles of chemotherapy with paclitaxel and carboplatin and tumor-debulking surgery. Ovarian carcinoma paraneoplastic nephrotic syndrome secondary to MCD is an extremely rare event, which is important to recognize since it is responsive to the standard chemotherapy.

  6. Maintaining Adequate CO2 Washout for an Advanced EMU via a New Rapid Cycle Amine Technology

    NASA Technical Reports Server (NTRS)

    Chullen, Cinda

    2011-01-01

    Over the past several years, NASA has realized tremendous progress in Extravehicular Activity (EVA) technology development. This has been evidenced by the progressive development of a new Rapic Cycle Amine (RCA) system for the Advanced Extravehicular Mobility Unit (AEMU) Portable Life Support Subsystem (PLSS). The PLSS is responsible for the life support of the crew member in the spacesuit. The RCA technology is responsible for carbon dioxide (CO2) and humidity control. Another aspect of the RCA is that it is on-back vacuum-regenerable, efficient, and reliable. The RCA also simplifies the PLSS schematic by eliminating the need for a condensing heat exchanger for humidity control in the current EMU. As development progresses on the RCA, it is important that the sizing be optimized so that the demand on the PLSS battery is minimized. As well, maintaining the CO2 washout at adequate levels during an EVA is an absolute requirement of the RCA and associated ventilation system. Testing has been underway in-house at NASA Johnson Space Center and analysis has been initiated to evaluate whether the technology provides exemplary performance in ensuring that the CO2 is removed sufficiently enough and the ventilation flow is adequate enough to maintain CO2 1 Project Engineer, Space Suit and Crew Survival Systems Branch, Crew and Thermal Systems Division, 2101 NASA Parkway, Houston, TX 77058/EC5. washout in the AEMU spacesuit helmet of the crew member during an EVA. This paper will review the recent developments of the RCA unit, the testing results performed in-house with a spacesuit simulator, and the associated analytical work along with insights from the medical aspect on the testing.

  7. Lost expression of DCC gene in ovarian cancer and its inhibition in ovarian cancer cells.

    PubMed

    Meimei, Liu; Peiling, Li; Baoxin, Li; Changmin, Li; Rujin, Zhuang; Chunjie, Hu

    2011-03-01

    Ovarian cancer is a leading cause of cancer-related women mortality in China. In recent years, the molecular mechanisms involved in ovarian carcinoma development and/or progression have been intensely studied, and several genes have been identified. Deleted in Colorectal Carcinoma (DCC), is an important tumor suppressor gene, which is inactivated in many kinds of tumors, and its function(s) is not clarified. Even though the lost expression of DCC occurred in later stages of multistep colorectal carcinogenesis, its contribution to the onset or progression of ovarian cancer is not fully understood. To investigate DCC expression in ovarian cancer, we studied 254 clinical samples by RT-PCR. Our results revealed that 52% malignant ovarian cancer did not express DCC gene. By contrast, DCC expression was observed in all normal ovary tissues and 80% benign ovarian tumors. Obviously, there was a significant correlation between DCC expression and ovarian cancer, especially in the epithelial ovarian cancer. The present study also suggested that the loss expression of DCC occurred more frequently in the cases of later clinical stage, higher pathological grade, and poorer prognosis. In the other part of this study, we further explored DCC expression after transfection in two kinds of ovarian cancer cell lines, namely SKOV3 cell and HO-8910 cell, using RT-PCR and immunocytochemistry. The results indicated that DCC expressed in SKOV3-DCC and HO-8910-DCC cells, and ultrastructural analysis showed the appearance of apoptotic features in them. Furthermore, cell growth was markedly down-regulated in above groups of cells, indicating that transfection with the DCC constructs can suppress the growth of tumor cells. In conclusion, our results suggest an association of lost expression of DCC with the ovarian cancer, and DCC gene may inhibit the growth of ovarian carcinoma cells. However, this result needs further trials with a larger sample. PMID:20054719

  8. 45 CFR 1182.15 - Institute responsibility for maintaining adequate technical, physical, and security safeguards to...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... secured room with a locking door. (3) Access to and use of a system of records shall be permitted only to... or upon his or her written request to the General Counsel. (5) Access to areas where a system of... ensure that all persons whose duties require access to and use of records contained in a system...

  9. 45 CFR 1182.15 - Institute responsibility for maintaining adequate technical, physical, and security safeguards to...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... secured room with a locking door. (3) Access to and use of a system of records shall be permitted only to... or upon his or her written request to the General Counsel. (5) Access to areas where a system of... ensure that all persons whose duties require access to and use of records contained in a system...

  10. 45 CFR 1182.15 - Institute responsibility for maintaining adequate technical, physical, and security safeguards to...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... technical, physical, and security safeguards to prevent unauthorized disclosure or destruction of manual and..., physical, and security safeguards to prevent unauthorized disclosure or destruction of manual and automatic..., physical, and security safeguards to prevent unauthorized disclosure or destruction of manual and...

  11. The treatment of early stage ovarian cancer.

    PubMed

    Young, R C

    1995-10-01

    Approximately one third of women with ovarian cancer present with localized disease. A series of recent studies have identified a population of patients who require only comprehensive surgical staging for optimal results and another group that may benefit from adjuvant therapy. A series of national and international studies are evaluating a variety of adjuvant treatments in prospective randomized trials that may enhance long-term survival in poor-prognosis early ovarian cancer. PMID:7481865

  12. Histomorphometric Evaluation of Superovulation Effect on Follicular Development after Autologous Ovarian Transplantation in Mice

    PubMed Central

    Raayat Jahromi, Alireza; Rahmanifar, Farhad; Ayaseh, Mohammad; Koohi-Hosseinabadi, Omid; Moghiminasr, Reza

    2015-01-01

    The effect of superovulation by pregnant mare serum gonadotropin (PMSG) on autologous transplanted ovaries in the lumbar muscles of mice was histomorphometrically evaluated using the indices of number and volume of different kind of follicles and volume of corpora lutea, ovary, and stroma. Angiogenesis was observed after mouse ovarian transplantation on days 14 and 21 after ovarian grafting. After transplantation, the total number and volume of primary and secondary follicles reduced, while PMSG superovulation increased the total number and total volume of tertiary follicles and also the ovarian volume after transplantation. Transplantation increased the average size of primary, secondary, and tertiary follicles. Therefore, primary and secondary follicles can survive after autologous transplantation but their reservations diminished by increasing the time of transplantation. However, number of tertiary follicles and their response to superovulation increased over time after transplantation. PMID:26693385

  13. Dynamic Nanoparticle-Based Flexible Sensors: Diagnosis of Ovarian Carcinoma from Exhaled Breath.

    PubMed

    Kahn, Nicole; Lavie, Ofer; Paz, Moran; Segev, Yakir; Haick, Hossam

    2015-10-14

    Flexible sensors based on molecularly modified gold nanoparticles (GNPs) were integrated into a dynamic cross-reactive diagnostic sensing array. Each bending state of the GNP-based flexible sensor gives unique nanoparticle spatial organization, altering the interaction between GNP ligands and volatile organic compounds (VOCs), which increases the amount of data obtainable from each sensor. Individual dynamic flexible sensor could selectively detect parts per billion (ppb) level VOCs that are linked with ovarian cancers in exhaled breath and discriminate them from environmental VOCs that exist in exhaled breath samples, but do not relate to ovarian cancer per se. Strain-related response successfully discriminated between exhaled breath collected from control subjects and those with ovarian cancer, with data from a single sensor being sufficient to obtain 82% accuracy, irrespective of important confounding factors, such as tobacco consumption and comorbidities. The approach raises the hope of achieving an extremely simple, inexpensive, portable, and noninvasive diagnostic procedure for cancer and other diseases. PMID:26352191

  14. Molecular Profiling of Clear Cell Ovarian Cancers

    PubMed Central

    Friedlander, Michael L.; Russell, Kenneth; Millis, Sherri; Gatalica, Zoran; Bender, Ryan; Voss, Andreas

    2016-01-01

    Background Advanced stage/recurrent clear cell ovarian cancers (CCOCs) are characterized by a low response to chemotherapy and a poor prognosis. There is growing interest in investigating novel/molecular targeted therapies in patients with CCOC in histotype-specific trials. However, CCOCs are not a uniform entity and comprise a number of molecular subtypes and it is unlikely that a single approach to treatment will be appropriate for all patients. The aim of this study was to analyze the results of a multiplatform profiling panel in CCOCs to identify potential therapeutic targets. Patients and Methods Tumor profiling was performed on 521 CCOCs. They were grouped into pure (n = 422) and mixed (n = 99) CCOC for analysis. Testing included a combination of DNA sequencing (including next-generation sequencing) using a 46-gene panel, immunohistochemistry, fluorescent or chromogenic in situ hybridization, and RNA fragment analysis. Results The most common findings were in the PIK3CA/Akt/mTOR pathway, with 61% of all CCOCs showing a molecular alteration in one of these pathway components. Next-generation sequencing revealed PIK3CA mutations in 50% of pure CCOCs. Significant differences were observed between pure and mixed CCOCs with respect to hormone receptor expression (9% vs 34.7% for ER, 13.45 vs 26.4% for PR), cMET (24.1% vs 11.6%), PD-1 tumor infiltrating lymphocytes (48.1% vs 100%), expression of PD-L1 (7.4% vs 25%), and TOPO1 (41% vs 27.1%) on immunohistochemistry, whereas next-generation sequencing revealed significant differences in mutation frequency in PIK3CA (50% vs 18.5%), TP53 (18.1% vs 57.7%), KRAS (12.4% vs 3.7%), and cMET (1.9% vs 11.1%). Conclusions This large study confirms that the PIK3CA/Akt/mTOR pathway is commonly altered in CCOCs, and highlights the significant differences between pure and mixed CCOCs. Clear cell ovarian cancers are molecularly heterogeneous and there are a number of potential therapeutic targets which could be tested in clinical

  15. Pembrolizumab, Bevacizumab, and Cyclophosphamide in Treating Patients With Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2016-09-02

    Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Serous Adenocarcinoma; Primary Peritoneal Serous Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

  16. The double-edged sword of ovarian cancer information for women at increased risk who have previously taken part in screening

    PubMed Central

    Smits, Stephanie; Boivin, Jacky; Menon, Usha; Brain, Kate

    2016-01-01

    Background Women at increased risk who decide not to have, or to delay, risk-reducing salpingo-oophorectomy have to rely on early diagnosis through symptom awareness and presenting to primary care as soon as possible in the absence of screening. However, little is known about the acceptability to women of this strategy. We aimed to gain an in-depth understanding of women’s perceptions and previous experiences of ovarian cancer symptom management, and the influences on ovarian cancer awareness and anticipated symptom presentation. Method Qualitative interviews were conducted with eight women at increased risk of ovarian cancer who had previously taken part in ovarian cancer screening and analysed using interpretative phenomenological analysis (IPA). Results Familial experience of ovarian cancer and perceived personal risk shaped women’s perceptions and behavioural responses to disease threat. Ovarian cancer information was perceived to be a double-edged sword, regarded as either useful for increasing knowledge and confidence in discussing symptom concerns with health professionals or to be avoided due to fears about cancer. Conclusion Women may be cautious about searching for information independently and in the absence of routine ovarian screening. Practice implications Thought needs to be given to how best to create and disseminate credible ovarian cancer symptom information materials. PMID:27433283

  17. Identification and confirmation of differentially expressed fucosylated glycoproteins in the serum of ovarian cancer patients using a lectin array and LC-MS/MS.

    PubMed

    Wu, Jing; Xie, Xiaolei; Liu, Yashu; He, Jintang; Benitez, Ricardo; Buckanovich, Ronald J; Lubman, David M

    2012-09-01

    In order to discover potential glycoprotein biomarkers in ovarian cancer, we applied a lectin array and Exactag labeling based quantitative glycoproteomics approach. A lectin array strategy was used to detect overall lectin-specific glycosylation changes in serum proteins from patients with ovarian cancer and those with benign conditions. Lectins, which showed significant differential response for fucosylation, were used to extract glycoproteins that had been labeled using isobaric chemical tags. The glycoproteins were then identified and quantified by LC-MS/MS, and five glycoproteins were found to be differentially expressed in the serum of ovarian cancer patients compared to benign diseases. The differentially expressed glycoproteins were further confirmed by lectin-ELISA and ELISA assay. Corticosteroid-binding globulin (CBG), serum amyloid p component (SAP), complement factor B (CFAB), and histidine-rich glycoprotein (HRG) were identified as potential markers for differentiating ovarian cancer from benign diseases or healthy controls. A combination of CBG and HRG (AUC = 0.825) showed comparable performance to CA125 (AUC = 0.829) in differentiating early stage ovarian cancer from healthy controls. The combination of CBG, SAP, and CA125 showed improved performance for distinguishing stage III ovarian cancer from benign diseases compared to CA125 alone. The ability of CBG, SAP, HRG, and CFAB to differentiate the serum of ovarian cancer patients from that of controls was tested using an independent set of samples. Our findings suggest that glycoprotein modifications may be a means to identify novel diagnostic markers for detection of ovarian cancer.

  18. Oocyte cryopreservation for fertility preservation in post-pubertal female children at risk for premature ovarian failure due to accelerated follicle loss in Turner Syndrome or cancer treatments

    PubMed Central

    Oktay, K; Bedoschi, G

    2014-01-01

    Objective To preliminarily study the feasibility of oocyte cryopreservation in post-pubertal girls aged between 13 and 15 years who were at risk for premature ovarian failure due to the accelerated follicle loss associated with Turner’s Syndrome or cancer treatments. Design Retrospective cohort and review of literature. Setting Academic fertility preservation unit. Participants Three girls diagnosed with Turner syndrome, one girl diagnosed with germ-cell tumor and one girl diagnosed with lymphoblastic leukemia. Interventions Assessment of ovarian reserve, ovarian stimulation, oocyte retrieval, in vitro maturation, and mature oocyte cryopreservation. Main Outcome Measure Response to ovarian stimulation, number of mature oocytes cryopreserved and complications, if any. Results Mean AMH, baseline FSH, Estradiol and antral follicle counts were 1.30 ± 0.39, 6.08 ± 2.63, 41.39 ± 24.68, 8.0 ± 3.2; respectively. In Turner girls the ovarian reserve assessment indicated already diminished ovarian reserve. Ovarian stimulation and oocyte cryopreservation was successfully performed in all female children referred for fertility preservation. A range of 4–11 mature oocytes (mean 8.1 ± 3.4) was cryopreserved without any complications. All girls tolerated the procedure well. Conclusions Oocyte cryopreservation is a feasible technique in selected female children at risk for premature ovarian failure. Further studies would be beneficial to test the success of oocyte cryopreservation in young girls. PMID:25214440

  19. Is CA72-4 a Useful Biomarker in Differential Diagnosis between Ovarian Endometrioma and Epithelial Ovarian Cancer?

    PubMed Central

    Anastasi, Emanuela; Manganaro, Lucia; Granato, Teresa; Benedetti Panici, Pierluigi; Frati, Luigi; Porpora, Maria Grazia

    2013-01-01

    Background. Surgical excision of ovarian endometriomas in patients desiring pregnancy has recently been criticized because of the risk of damage to healthy ovarian tissue and consequent reduction of ovarian reserve. A correct diagnosis in cases not scheduled for surgery is therefore mandatory in order to avoid unexpected ovarian cancer misdiagnosis. Endometriosis is often associated with high levels of CA125. This marker is therefore not useful for discriminating ovarian endometrioma from ovarian malignancy. The aim of this study was to establish if the serum marker CA72-4 could be helpful in the differential diagnosis between ovarian endometriosis and epithelial ovarian cancer. Methods. Serums CA125 and CA72-4 were measured in 72 patients with ovarian endometriomas and 55 patients with ovarian cancer. Results. High CA125 concentrations were observed in patients with ovarian endometriosis and in those with ovarian cancer. A marked difference in CA72-4 values was observed between women with ovarian cancer (71.0%) and patients with endometriosis (13.8%) (P < 0.0001). Conclusions. This study suggests that CA72-4 determination can be useful to confirm the benign nature of ovarian endometriomas in women with high CA125 levels. PMID:24191126

  20. Factors regulating ovarian function in pigs.

    PubMed

    Madej, A; Lang, A; Brandt, Y; Kindahl, H; Madsen, M T; Einarsson, S

    2005-08-01

    The hormonal interactions of the hypothalamic-pituitary-ovarian-uterine axis are accountable for a normal reproduction in female pigs. It is of importance to have knowledge of estrous symptoms and hormonal profiles around ovulation. The introduction of the transrectal ultrasonography in sows has given us the possibility to study ovarian activity in conscious animals and relate the timing of estrus to ovulation. Combining this technique with measuring of several hormones like luteinizing hormone (LH), follicle-stimulating hormone (FSH), inhibin, estradiol, progesterone, insulin-like growth hormone I (IGF-I), prostaglandin F2alpha (PGF2alpha) metabolite, oxytocin, facilitate our knowledge about the sequence of ovarian events. Evidence suggests that activation of the hypothalamic-pituitary-adrenal axis may hamper the normal gonadotropin secretion and in consequence, the ovarian function. The metabolic status during lactation, weaning of piglets and social stress might affect onset of ovarian activity and the related estrous behavior. The role of seminal plasma, artificial insemination and presence of the boar might also be included as factors regulating the temporal kinetics of ovulation, corpus luteum development, uterine function and steroid production in the ovary. Studies using a simulated stress by means of adrenocorticotrophic hormone (ACTH) administration or food deprivation are tools in understanding how the ovary is susceptible to impairment. The intention of this paper is to review current knowledge concerning the endocrine aspects of normal and stress-influenced ovarian function in pigs.

  1. Unbalanced Estrogen Metabolism in Ovarian Cancer

    PubMed Central

    Zahid, Muhammad; Beseler, Cheryl L.; Hall, James B.; LeVan, Tricia; Cavalieri, Ercole L.; Rogan, Eleanor G.

    2013-01-01

    Greater exposure to estrogens is a risk factor for ovarian cancer. To investigate the role of estrogens in ovarian cancer, a spot urine sample and a saliva sample were obtained from 33 women with ovarian cancer and 34 age-matched controls. Thirty-eight estrogen metabolites, conjugates and DNA adducts were analyzed in the urine samples by using ultraperformance liquid chromatography/tandem mass spectrometry, and the ratio of adducts to metabolites and conjugates was calculated for each sample. The ratio of depurinating estrogen-DNA adducts to estrogen metabolites and conjugates was significantly higher in cases compared to controls (p<0.0001), demonstrating high specificity and sensitivity. DNA was purified from the saliva samples and analyzed for genetic polymorphisms in the genes for two estrogen-metabolizing enzymes. Women with two low-activity alleles of catechol-O-methyltransferase plus one or two high-activity alleles of cytochrome P450 1B1 had higher levels of estrogen-DNA adducts and were more likely to have ovarian cancer. These findings indicate that estrogen metabolism is unbalanced in ovarian cancer and suggest that formation of estrogen-DNA adducts plays a critical role in the initiation of ovarian cancer. PMID:24170413

  2. Ormeloxifene efficiently inhibits ovarian cancer growth

    PubMed Central

    Maher, Diane M.; Khan, Sheema; Nordquist, Jordan; Ebeling, Mara C.; Bauer, Nichole A.; Kopel, Lucas; Singh, Man Mohan; Halaweish, Fathi; Bell, Maria C.; Jaggi, Meena; Chauhan, Subhash C.

    2014-01-01

    Ovarian cancer continues to be a leading cause of cancer related deaths for women. Anticancer agents effective against chemo-resistant cells are greatly needed for ovarian cancer treatment. Repurposing drugs currently in human use is an attractive strategy for developing novel cancer treatments with expedited translation into clinical trials. Therefore, we examined whether ormeloxifene (ORM), a non-steroidal Selective Estrogen Receptor Modulator (SERM) currently used for contraception, is therapeutically effective at inhibiting ovarian cancer growth. We report that ORM treatment inhibits cell growth and induces apoptosis in ovarian cancer cell lines, including cell lines resistant to cisplatin. Furthermore, ORM treatment decreases Akt phosphorylation, increases p53 phosphorylation, and modulates the expression and localization patterns of p27, cyclin E, cyclin D1, and CDK2. In a pre-clinical xenograft mouse ORM treatment significantly reduces tumorigenesis and metastasis. These results indicate that ORM effectively inhibits the growth of cisplatin resistant ovarian cancer cells. ORM is currently in human use and has an established record of patient safety. Our encouraging in vitro and pre-clinical in vivo findings indicate that ORM is a promising candidate for the treatment of ovarian cancer. PMID:25306892

  3. Ultrasound measurement of the ovarian volume.

    PubMed

    Andolf, E; Jörgensen, C; Svalenius, E; Sundén, B

    1987-01-01

    The ovaries of 377 women between the age of 40 and 70 years were measured by ultrasound. About one third of the patients were postmenopausal. Mean value, standard deviation and S.E.M. of the ovarian volume were calculated and related to age, parity and menstrual cycle. Ovarian size decreased with age in all women but bore no relation to parity and day of menstrual cycle in the menstruating group of women over 40 years of age. A diagram of the ovarian volume related to age is presented. In postmenopausal women the volume was related to estrogen treatment, age, parity and years since menopause. In the group of women receiving orally administered estrogens for at least a year the p-values for all parameters were greater than 0.005. Furthermore, the ovarian volume of women under hormonal treatment did not decrease with age. On the other hand the most important factor for ovarian size in subjects not receiving estrogen treatment was age (p = 0.0056). The results presented here will serve as a prerequisite for sonar examination of the ovaries in women at high risk for development of ovarian carcinoma.

  4. Environmental and developmental origins of ovarian reserve.

    PubMed

    Richardson, M C; Guo, M; Fauser, B C J M; Macklon, N S

    2014-01-01

    BACKGROUND Oocyte number is established early in life before a gradual loss of this ovarian reserve during reproductive life until oocyte availability becomes limiting at the menopause. Although there is a large genetic component to the ovarian reserve achieved before birth, other influences including the maternal endocrine and nutritional milieu, and environmental factors may represent important developmental determinants. Environmental and nutritional factors may also modify the downward trajectory of ovarian reserve in adult life. The combination of these early and later life influences has the potential to lead to diminished ovarian reserve, compromising fertility in later reproductive years and altering age at natural menopause. METHODS Literature searches of the ISI Web of Knowledge database were carried out using the main terms 'ovarian reserve' and 'menopause AND age' in conjunction with a range of other terms encompassing a variety of factors with potential effects on ovarian reserve. The various searches were inspected manually and the relevant papers selected for critical analysis and interpretation. RESULTS Evidence was identified supporting the view that elevated prenatal androgens have an adverse effect on the early establishment of ovarian reserve, although the implications for ovarian reserve in the polycystic ovary syndrome (which may also be programmed through prenatal androgen exposure) remain uncertain. Recent evidence is cited suggesting that effects of maternal nutrient restriction on ovarian reserve may also involve changes in prenatal androgen exposure. A general rationale is developed through examination of evidence which emphasizes the roles of the aryl hydrocarbon receptor (AHR) and the estrogen receptor (ER) systems in ovarian reserve modulation. Because of their similarity to the natural ligands, many environmental compounds have the ability to bind to these receptors (albeit at lower affinities) and thereby have the potential to

  5. Nuclear COMMD1 Is Associated with Cisplatin Sensitivity in Ovarian Cancer

    PubMed Central

    Wisman, G. Bea A.; Duiker, Evelien; Reyners, Anna K. L.; van der Zee, Ate G. J.; van de Sluis, Bart; van Vugt, Marcel A. T. M.

    2016-01-01

    Copper metabolism MURR1 domain 1 (COMMD1) protein is a multifunctional protein, and its expression has been correlated with patients’ survival in different types of cancer. In vitro studies revealed that COMMD1 plays a role in sensitizing cancer cell lines to cisplatin, however, the mechanism and its role in platinum sensitivity in cancer has yet to be established. We evaluated the role of COMMD1 in cisplatin sensitivity in A2780 ovarian cancer cells and the relation between COMMD1 expression and response to platinum-based therapy in advanced stage high-grade serous ovarian cancer (HGSOC) patients. We found that elevation of nuclear COMMD1 expression sensitized A2780 ovarian cancer cells to cisplatin-mediated cytotoxicity. This was accompanied by a more effective G2/M checkpoint, and decreased protein expression of the DNA repair gene BRCA1, and the apoptosis inhibitor BCL2. Furthermore, COMMD1 expression was immunohistochemically analyzed in two tissue micro-arrays (TMAs), representing a historical cohort and a randomized clinical trial-based cohort of advanced stage HGSOC tumor specimens. Expression of COMMD1 was observed in all ovarian cancer samples, however, specifically nuclear expression of COMMD1 was only observed in a subset of ovarian cancers. In our historical cohort, nuclear COMMD1 expression was associated with an improved response to chemotherapy (OR = 0.167; P = 0.038), although this association could not be confirmed in the second cohort, likely due to sample size. Taken together, these results suggest that nuclear expression of COMMD1 sensitize ovarian cancer to cisplatin, possibly by modulating the G2/M checkpoint and through controlling expression of genes involved in DNA repair and apoptosis. PMID:27788210

  6. Palmar fasciitis and arthritis with ovarian and non-ovarian carcinomas. New syndrome.

    PubMed

    Shiel, W C; Prete, P E; Jason, M; Andrews, B S

    1985-11-01

    Paraneoplastic syndromes affect a variety of organ systems and often suggest occult malignancy. Recently, a distinct syndrome of palmar fasciitis and arthritis has been associated with ovarian carcinomas. The two cases presented illustrate the fasciitis-arthritis association with other non-ovarian malignancies and suggest an immunologic cause for this disorder.

  7. Intraperitoneal Bortezomib and Carboplatin in Treating Patients With Persistent or Recurrent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2016-06-21

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

  8. Features of ovarian cancer in Lynch syndrome (Review)

    PubMed Central

    NAKAMURA, KANAKO; BANNO, KOUJI; YANOKURA, MEGUMI; IIDA, MIHO; ADACHI, MASATAKA; MASUDA, KENTA; UEKI, ARISA; KOBAYASHI, YUSUKE; NOMURA, HIROYUKI; HIRASAWA, AKIRA; TOMINAGA, EIICHIRO; AOKI, DAISUKE

    2014-01-01

    Lynch syndrome is a hereditary ovarian cancer with a prevalence of 0.9–2.7%. Lynch syndrome accounts for 10–15% of hereditary ovarian cancers, while hereditary breast and ovarian cancer syndrome accounts for 65–75% of these cancers. The lifetime risk for ovarian cancer in families with Lynch syndrome is ~8%, which is lower than colorectal and endometrial cancers, and ovarian cancer is not listed in the Amsterdam Criteria II. More than half of sporadic ovarian cancers are diagnosed in stage III or IV, but ≥80% of ovarian cancers in Lynch syndrome are diagnosed in stage I or II. Ovarian cancers in Lynch syndrome mostly have non-serous histology and different properties from those of sporadic ovarian cancers. A screening method for ovarian cancers in Lynch syndrome has yet to be established and clinical studies of prophylactic administration of oral contraceptives are not available. However, molecular profiles at the genetic level indicate that ovarian cancer in Lynch syndrome has a more favorable prognosis than sporadic ovarian cancer. Inhibitors of the phosphatidylinositol 3-kinase/mammalian target of the rapamycin pathway and anti-epidermal growth factor antibodies may have efficacy for the disease. To the best of our knowledge, this is the first review focusing on ovarian cancer in Lynch syndrome. PMID:25279173

  9. 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.

  10. Conventional chemotherapy and oncogenic pathway targeting in ovarian carcinosarcoma using a patient-derived tumorgraft.

    PubMed

    Glaser, Gretchen; Weroha, S John; Becker, Marc A; Hou, Xiaonan; Enderica-Gonzalez, Sergio; Harrington, Sean C; Haluska, Paul

    2015-01-01

    Ovarian carcinosarcoma is a rare subtype of ovarian cancer with poor clinical outcomes. The low incidence of this disease makes accrual to large clinical trials challenging. However, studies have shown that treatment responses in patient-derived xenograft (PDX) models correlate with matched-patient responses in the clinic, supporting their use for preclinical testing of standard and novel therapies. An ovarian carcinosarcoma PDX is presented herein and showed resistance to carboplatin and paclitaxel (similar to the patient) but exhibited significant sensitivity to ifosfamide and paclitaxel. The PDX demonstrated overexpression of EGFR mRNA and gene amplification by array comparative genomic hybridization (log2 ratio 0.399). EGFR phosphorylation was also detected. Angiogensis and insulin-like growth factor pathways were also implicated by overexpression of VEGFC and IRS1. In order to improve response to chemotherapy, the PDX was treated with carboplatin/paclitaxel with or without a pan-HER and VEGF inhibitor (BMS-690514) but there was no tumor growth inhibition or improved animal survival, which may be explained by a KRAS mutation. Resistance was also observed when the IGF-1R inhibitor BMS-754807 was combined with carboplatin/paclitaxel. Because poly (ADP-ribose) polymerase inhibitors have activity in ovarian cancer patients, with and without BRCA mutations, ABT-888 was also tested but found to have no activity. Pathogenic mutations were also detected in TP53 and PIK3CA. In conclusion, ifosfamide/paclitaxel was superior to carboplatin/paclitaxel in this ovarian carcinosarcoma PDX and gene overexpression or amplification alone was not sufficient to predict response to targeted therapy. Better predictive markers of response are needed. PMID:25962155

  11. Elevated blood plasma concentrations of active ghrelin and obestatin in benign ovarian neoplasms and ovarian cancers.

    PubMed

    Markowska, A; Ziółkowska, A; Jaszczyńska-Nowinka, K; Madry, R; Malendowicz, L K

    2009-01-01

    Both ghrelin and obestatin are derived from preproghrelin by post-translational processing. The two peptides are secreted into the blood but circulating levels of these peptides have not been assessed in women with ovarian tumours. Therefore, the purpose of this study was to evaluate peripheral blood concentrations of active and total ghrelin and obestatin in patients with benign ovarian tumours and those with ovarian cancer. The studies were conducted on 22 patients operated due to benign ovarian tumours, and 31 patients operated due to ovarian cancer. A control group consisted of 32 women, 24 to 65 years of age. Both in women with benign ovarian tumours and those with ovarian cancer blood concentrations of active ghrelin and obestatin were higher than in the control group (active ghrelin: 90 +/- 4, 84 +/- 4 and 56 +/- 9 pg/ml, respectively, obestatin: 660 +/- 36; 630 +/- 30 and 538 +/- 31 ng/ml (x +/- SE), respectively). In contrast, total ghrelin concentrations in blood were similar in the studied groups. The alterations resulted in increased values of active to total ghrelin concentration ratio in the peripheral blood of patients with benign ovarian tumours or with ovarian cancer (0.79 +/- 0.02 and 0.93 +/- 0.05, respectively vs 0.58 +/- 0.02 in the control group). Due to the absence of any convincing proof for the presence of a functional GHS-R-1a receptor for ghrelin in human ovaries it did not seem probable that the observed elevated levels of active ghrelin and obestatin were directly linked to development of ovarian tumours.

  12. Cisplatin and Paclitaxel in Treating Patients With Stage IIB, Stage IIC, Stage III, or Stage IV Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cavity Cancer

    ClinicalTrials.gov

    2014-12-29

    Chemotherapeutic Agent Toxicity; Endometrial Adenocarcinoma; Fallopian Tube Carcinoma; Gastrointestinal Complication; Malignant Ovarian Mixed Epithelial Tumor; Neurotoxicity Syndrome; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Primary Peritoneal Carcinoma; Stage II Ovarian Cancer; Stage III Ovarian Cancer; Stage IV Ovarian Cancer; Undifferentiated Ovarian Carcinoma

  13. Quantitative imaging reveals heterogeneous growth dynamics and treatment-dependent residual tumor distributions in a three-dimensional ovarian cancer model

    NASA Astrophysics Data System (ADS)

    Celli, Jonathan P.; Rizvi, Imran; Evans, Conor L.; Abu-Yousif, Adnan O.; Hasan, Tayyaba

    2010-09-01

    Three-dimensional tumor models have emerged as valuable in vitro research tools, though the power of such systems as quantitative reporters of tumor growth and treatment response has not been adequately explored. We introduce an approach combining a 3-D model of disseminated ovarian cancer with high-throughput processing of image data for quantification of growth characteristics and cytotoxic response. We developed custom MATLAB routines to analyze longitudinally acquired dark-field microscopy images containing thousands of 3-D nodules. These data reveal a reproducible bimodal log-normal size distribution. Growth behavior is driven by migration and assembly, causing an exponential decay in spatial density concomitant with increasing mean size. At day 10, cultures are treated with either carboplatin or photodynamic therapy (PDT). We quantify size-dependent cytotoxic response for each treatment on a nodule by nodule basis using automated segmentation combined with ratiometric batch-processing of calcein and ethidium bromide fluorescence intensity data (indicating live and dead cells, respectively). Both treatments reduce viability, though carboplatin leaves micronodules largely structurally intact with a size distribution similar to untreated cultures. In contrast, PDT treatment disrupts micronodular structure, causing punctate regions of toxicity, shifting the distribution toward smaller sizes, and potentially increasing vulnerability to subsequent chemotherapeutic treatment.

  14. Drugs Approved for Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

    MedlinePlus

    ... Professionals Questions to Ask about Your Treatment Research Drugs Approved for Ovarian, Fallopian Tube, or Primary Peritoneal ... primary peritoneal cancer that are not listed here. Drugs Approved for Ovarian, Fallopian Tube, or Primary Peritoneal ...

  15. Breast and Ovarian Cancer and Family History Risk Categories

    MedlinePlus

    ... Diseases Genomic Resources Breast and Ovarian Cancer and Family History Risk Categories Recommend on Facebook Tweet Share ... Screening. U.S. Preventive Services Task Force. February 2016. Family Health History, Breast and Ovarian Cancer Risk, and ...

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

    MedlinePlus

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

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

    MedlinePlus

    ... cancer? What should you ask your doctor about ovarian cancer? It is important for you to have honest, ... are some questions to consider: What type of ovarian cancer do I have? Has my cancer spread beyond ...

  18. Know Your Risk for Ovarian Cancer -- and The Symptoms

    MedlinePlus

    ... news/fullstory_160881.html Know Your Risk for Ovarian Cancer -- and the Symptoms Because early signs are often ... is needed in the prevention and treatment of ovarian cancer, according to a doctor who specializes in the ...

  19. 6 Common Cancers - Gynecologic Cancers Cervical, Endometrial, and Ovarian

    MedlinePlus

    ... Bar Home Current Issue Past Issues 6 Common Cancers - Gynecologic Cancers Cervical, Endometrial, and Ovarian Past Issues / Spring 2007 ... of this page please turn Javascript on. Gynecologic Cancers Cervical, Endometrial, and Ovarian NCI estimates that endometrial, ...

  20. [Sonographic diagnosis of presumed benign ovarian tumors].

    PubMed

    Marret, H; Cayrol, M

    2013-12-01

    To discriminate ovarian lesions is of particular importance in gynecological practice. Two main problems need answers: discrimination of benign and malignant adnexal masses and choice of the appropriate surgical treatment if necessary. Nearly 2% of the adnexal masses are ovarian carcinomas or borderline tumors. It is now, well established that ultrasonography is the gold standard for ovarian cyst diagnosis. The purpose of this data was to review the literature and to establish, with the evidence base medicine model, which parameters and existing diagnostic models using ultrasound and Doppler perform best in the evaluation of adnexal masses. Transvaginal sonography has demonstrated considerable advantage over conventional transabdominal sonography. However, transparietal sonography is still useful in large tumors. Definition of the nomenclature and classification was done and should be used. Unilocular ovarian cyst characterization seems easy using sonography and Doppler. In front of complication, discrimination of such functional cyst may be difficult but spontaneous regression confirms usually the expectative management. Dermoid cysts and endometriomas seem to be easier to discriminate from other adnexal masses. Ultrasound and morphologic parameters have a sensitivity of about 90% and a specificity of 80%; that makes this exam the gold standard for ovarian masses diagnosis. Only 50% of ovarian masses are characterized by sonography. Scoring systems help to differentiate benign from malignant masses (sensitivity of about 90%). Logistic regression and models are good methods especially for LR1 and 2 and RMI and may be useful for malignancy prediction but are difficult to use in current practice. Expert diagnosis is a subjective but most important performing parameter. Any suspicious ovarian mass or not easily diagnosed mass requires sonography by an expert, which can first use all the techniques and the different parameters to discriminate benign and malignant