50 CFR Table 39 to Part 679 - Amendment 80 Vessels That May Be Used to Directed Fish for Flatfish in the GOA

Code of Federal Regulations, 2012 CFR

2012-10-01

... 50 Wildlife and Fisheries 13 2012-10-01 2012-10-01 false Amendment 80 Vessels That May Be Used to Directed Fish for Flatfish in the GOA 39 Table 39 to Part 679 Wildlife and Fisheries FISHERY CONSERVATION... Vessels That May Be Used to Directed Fish for Flatfish in the GOA Column A: Name of Amendment 80 vessel...

50 CFR Table 39 to Part 679 - Amendment 80 Vessels That May Be Used to Directed Fish for Flatfish in the GOA

Code of Federal Regulations, 2010 CFR

2010-10-01

... 50 Wildlife and Fisheries 9 2010-10-01 2010-10-01 false Amendment 80 Vessels That May Be Used to Directed Fish for Flatfish in the GOA 39 Table 39 to Part 679 Wildlife and Fisheries FISHERY CONSERVATION... Vessels That May Be Used to Directed Fish for Flatfish in the GOA Column A: Name of Amendment 80 vessel...

Orchestrating change: The thyroid hormones and GI-tract development in flatfish metamorphosis.

PubMed

Gomes, A S; Alves, R N; Rønnestad, I; Power, D M

2015-09-01

Metamorphosis in flatfish (Pleuronectiformes) is a late post-embryonic developmental event that prepares the organism for the larval-to-juvenile transition. Thyroid hormones (THs) play a central role in flatfish metamorphosis and the basic elements that constitute the thyroid axis in vertebrates are all present at this stage. The advantage of using flatfish to study the larval-to-juvenile transition is the profound change in external morphology that accompanies metamorphosis making it easy to track progression to climax. This important lifecycle transition is underpinned by molecular, cellular, structural and functional modifications of organs and tissues that prepare larvae for a successful transition to the adult habitat and lifestyle. Understanding the role of THs in the maturation of organs and tissues with diverse functions during metamorphosis is a major challenge. The change in diet that accompanies the transition from a pelagic larvae to a benthic juvenile in flatfish is associated with structural and functional modifications in the gastrointestinal tract (GI-tract). The present review will focus on the maturation of the GI-tract during metamorphosis giving particular attention to organogenesis of the stomach a TH triggered event. Gene transcripts and biological processes that are associated with GI-tract maturation during Atlantic halibut metamorphosis are identified. Gene ontology analysis reveals core biological functions and putative TH-responsive genes that underpin TH-driven metamorphosis of the GI-tract in Atlantic halibut. Deciphering the specific role remains a challenge. Recent advances in characterizing the molecular, structural and functional modifications that accompany the appearance of a functional stomach in Atlantic halibut are considered and future research challenges identified. Copyright © 2014 Elsevier Inc. All rights reserved.

Age compositions of flatfish stocks as determined by a new otolithometric method, its application in the estimation of growth, spawning potential and fisheries management

NASA Astrophysics Data System (ADS)

Katayama, Satoshi; Yamamoto, Masayuki; Gorie, Shigeaki

2010-11-01

We developed an ageing methodology and examined age composition of three flatfish stocks inhabiting the Seto Inland Sea, Japan. Ages were difficult to determine for three-lined tongue sole ( Cynoglossus abbreviates) and ridged-eye flounder ( Pleuronichthys cornutus) because the first year annulus ring was often indistinct; therefore, we used directional change in otolith growth to distinguish it. Sectioning and etching methods were powerful tools for identifying annual checks for red tongue sole ( Cynoglossus joyneri). Using these ageing methods, we determined age-length relationships and growth curves. The age composition of the populations studied and of the landings showed that a large proportion of the latter consisted of individuals under the mean age of sexual maturity, thereby reducing the percent spawning potential ratio (%SPR) to ≈ 20% for all species. These findings suggest that fishing pressure on immature fish is leading to overfishing of these flatfish stocks.

Flatfish monophyly refereed by the relationship of Psettodes in Carangimorphariae.

PubMed

Shi, Wei; Chen, Shixi; Kong, Xiaoyu; Si, Lizhen; Gong, Li; Zhang, Yanchun; Yu, Hui

2018-05-25

The monophyly of flatfishes has not been supported in many molecular phylogenetic studies. The monophyly of Pleuronectoidei, which comprises all but one family of flatfishes, is broadly supported. However, the Psettodoidei, comprising the single family Psettodidae, is often found to be most closely related to other carangimorphs based on substantial sequencing efforts and diversely analytical methods. In this study, we examined why this particular result is often obtained. The mitogenomes of five flatfishes were determined. Select mitogenomes of representative carangimorph species were further employed for phylogenetic and molecular clock analyses. Our phylogenetic results do not fully support Psettodes as a sister group to pleuronectoids or other carangimorphs. And results also supported the evidence of long-branch attraction between Psettodes and the adjacent clades. Two chronograms, derived from Bayesian relaxed-clock methods, suggest that over a short period in the early Paleocene, a series of important evolutionary events occurred in carangimorphs. Based on insights provided by the molecular clock, we propose the following evolutionary explanation for the difficulty in determining the phylogenetic position of Psettodes: The initial diversification of Psettodes was very close in time to the initial diversification of carangimorphs, and the primary diversification time of pleuronectoids, the other suborder of flatfishes, occurred later than that of some percomorph taxa. Additionally, the clade of Psettodes is long and naked branch, which supports the uncertainty of its phylogenetic placement. Finally, we confirmed the monophyly of flatfishes, which was accepted by most ichthyologists.

On factors structuring the flatfish assemblage in the southern North Sea

NASA Astrophysics Data System (ADS)

Piet, G. J.; Pfisterer, A. B.; Rijnsdorp, A. D.

1998-09-01

Ten species of flatfish were studied to see to what extent interspecific competition influences their diet or spatial distribution and whether the potential of these flatfish species to avoid interspecific competition through resource partitioning is constrained by specific morphological characteristics. For this, seven morphological characteristics were measured, diet composition was determined from gut content analyses and overlap in distribution was determined from the co-occurrence in trawl hauls. Canonical correspondence analysis revealed the morphological characteristics that were most strongly correlated with the diet composition. Based on these findings the mouth gape was considered to be the most important morphological constraint affecting the choice of food. Two resource dimensions were distinguished along which interspecific competition can act on the flatfish assemblage: the trophic dimension (diet composition) and the spatial dimension (distribution). Resource partitioning was observed along both dimensions separately and, more importantly, the degree of resource partitioning along the two dimensions was negatively correlated. Especially the latter was considered strong circumstantial evidence that interspecific competition is a major factor structuring the flatfish assemblage. Resource partitioning along the two resource dimensions increased with decreasing mouth gape, suggesting that interspecific competition mainly acts on the small-mouthed fish, i.e. juveniles.

Myostatin inhibitory region of fish (Paralichthys olivaceus) myostatin-1 propeptide.

PubMed

Lee, Sang Beum; Kim, Jeong Hwan; Jin, Deuk-Hee; Jin, Hyung-Joo; Kim, Yong Soo

2016-01-01

Myostatin (MSTN) is a potent negative regulator of skeletal muscle growth, and its activity is suppressed by MSTN propeptide (MSTNpro), the N-terminal part of MSTN precursor cleaved during post-translational MSTN processing. The current study examined which region of flatfish (Paralichthys olivaceus) MSTN-1 propeptide (MSTN1pro) is critical for MSTN inhibition. Six different truncated forms of MSTN1pro containing N-terminal maltose binding protein (MBP) as a fusion partner were expressed in Escherichia coli, and partially purified by an affinity chromatography for MSTN-inhibitory activity examination. Peptides covering different regions of flatfish MSTN1pro were also synthesized for MSTN-inhibitory activity examination. A MBP-fused MSTN1pro region consisting of residues 45-100 had the same MSTN-inhibitory potency as the full sequence flatfish MSTN1pro (residues 23-265), indicating that the region of flatfish MSTN1pro consisting of residues 45-100 is sufficient to maintain the full MSTN-inhibitory capacity. A MBP-fused MSTN1pro region consisting of residues 45-80 (Pro45-80) also showed MSTN-inhibitory activity with a lower potency, and the Pro45-80 demonstrated its MSTN binding capacity in a pull-down assay, indicating that the MSTN-inhibitory capacity of Pro45-80 is due to its binding to MSTN. Flatfish MSTN1pro synthetic peptides covering residues 45-65, 45-70, and 45-80 demonstrated MSTN-inhibitory activities, but not the synthetic peptide covering residues 45-54, indicating that residues 45-65 of flatfish MSTN1pro are essential for MSTN inhibition. In conclusion, current study show that like the mammalian MSTNpro, the MSTN-inhibitory region of flatfish MSTN1pro resides near its N-terminus, and imply that smaller sizes of MSTNpro can be effectively used in various applications designed for MSTN inhibition. Copyright © 2016 Elsevier Inc. All rights reserved.

Roles of insulin-like growth factors in metamorphic development of turbot (Scophthalmus maximus).

PubMed

Jia, Yudong

2018-01-31

Larval turbot (Scophthalmus maximus) undergo metamorphosis, a late post-embryonic developmental event that precedes juvenile transition. Insulin-like growth factors (IGFs) are important endocrine/autocrine/paracrine factors that provide essential signals to control of the embryonic and postnatal development of vertebrate species, including fish. Accumulating evidence suggests that IGFs are involved in regulating the metamorphic development of flatfish. This mini review focus on the functions of all known IGFs (IGF-I and IGF-II) during the metamorphic development of turbot. Information about IGFs and insulin-like growth factors binding proteins (IGFBPs) from other teleosts is also included in this review to provide an overview of IGFs functions in the metamorphic development of turbot. These findings may enhance our understanding of the potential roles of the IGFs system in controlling of flatfish metamorphosis and contributing to the improvement of broodstock management strategies for larval turbot. Copyright © 2018 Elsevier Inc. All rights reserved.

Shallow-water habitat use by Bering Sea flatfishes along the central Alaska Peninsula

NASA Astrophysics Data System (ADS)

Hurst, Thomas P.

2016-05-01

Flatfishes support a number of important fisheries in Alaskan waters and represent major pathways of energy flow through the ecosystem. Despite their economic and ecological importance, little is known about the use of habitat by juvenile flatfishes in the eastern Bering Sea. This study describes the habitat characteristics of juvenile flatfishes in coastal waters along the Alaska Peninsula and within the Port Moller-Herendeen Bay system, the largest marine embayment in the southern Bering Sea. The two most abundant species, northern rock sole and yellowfin sole, differed slightly in habitat use with the latter occupying slightly muddier substrates. Both were more common along the open coastline than they were within the bay, whereas juvenile Alaska plaice were more abundant within the bay than along the coast and used shallow waters with muddy, high organic content sediments. Juvenile Pacific halibut showed the greatest shift in distribution between age classes: age-0 fish were found in deeper waters (~ 30 m) along the coast, whereas older juveniles were found in the warmer, shallow waters within the bay, possibly due to increased thermal opportunities for growth in this temperature-sensitive species. Three other species, starry flounder, flathead sole, and arrowtooth flounder, were also present, but at much lower densities. In addition, the habitat use patterns of spring-spawning flatfishes (northern rock sole, Pacific halibut, and Alaska plaice) in this region appear to be strongly influenced by oceanographic processes that influence delivery of larvae to coastal habitats. Overall, use of the coastal embayment habitats appears to be less important to juvenile flatfishes in the Bering Sea than in the Gulf of Alaska.

Bioaccumulation of mercury in the trophic chain of flatfish from the Baltic Sea.

PubMed

Polak-Juszczak, Lucyna

2012-10-01

Mercury concentrations in three flatfish species - flounder (Platichtys flesus), plaice (Pleuronectes platessa), and Baltic turbot (Scophthalmus maximus), netted in the southern Baltic Sea were assessed and compared to concentrations of this metal in sediments, sea water, and flatfish food - bivalve Macoma balthica, isopod Saduria entomon, and sprat (Sprattus sprattus). Collected simultaneously with flatfish in 2009 and 2010. Different concentrations of mercury depending on species, tissue or organ, sex, individual length, kind of food, and region were determined. The muscle tissues of turbot had the highest concentrations of the metal. The bioaccumulation (BF) and biomagnification (BMF) factors has been counted showing that the muscle tissues of turbot have maximum affinity for mercury, and thus best reflected the metal contamination of the Baltic Sea environment. The data suggest that the common Baltic turbot (S. maximus) is an important model species, suitable and cost-effective to biomonitor environmental mercury pollution for ecological research. Copyright © 2012 Elsevier Ltd. All rights reserved.

How the Central American Seaway and an ancient northern passage affected flatfish diversification.

PubMed

Byrne, Lisa; Chapleau, François; Aris-Brosou, Stéphane

2018-05-21

While the natural history of flatfish has been debated for decades, the mode of diversification of this biologically and economically important group has never been elucidated. To address this question, we assembled the largest molecular data set to date, covering > 300 species (out of ca. 800 extant), from 13 of the 14 known families over nine genes, and employed relaxed molecular clocks to uncover their patterns of diversification. As the fossil record of flatfish is contentious, we used sister species distributed on both sides of the American continent to calibrate clock models based on the closure of the Central American Seaway (CAS), and on their current species range. We show that flatfish diversified in two bouts, as species that are today distributed around the Equator diverged during the closure of CAS, while those with a northern range diverged after this, hereby suggesting the existence of a post-CAS closure dispersal for these northern species, most likely along a trans-Arctic northern route, a hypothesis fully compatible with paleogeographic reconstructions.

50 CFR Figure 1 to Part 660... - Diagram of Selective Flatfish Trawl

Code of Federal Regulations, 2014 CFR

2014-10-01

... 50 Wildlife and Fisheries 13 2014-10-01 2014-10-01 false Diagram of Selective Flatfish Trawl 1 Figure 1 to Part 660, Subpart D Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE (CONTINUED) FISHERIES OFF WEST COAST STATES...

50 CFR 679.82 - Rockfish Program use caps and sideboard limits.

Code of Federal Regulations, 2013 CFR

2013-10-01

... not participate in directed fishing for arrowtooth flounder, deep-water flatfish, and rex sole in the GOA (or in waters adjacent to the GOA when arrowtooth flounder, deep-water flatfish, and rex sole... authority of all eligible LLP licenses in the catcher/processor sector. (ii) For the deep-water halibut PSC...

50 CFR 679.82 - Rockfish Program use caps and sideboard limits.

Code of Federal Regulations, 2014 CFR

2014-10-01

... not participate in directed fishing for arrowtooth flounder, deep-water flatfish, and rex sole in the GOA (or in waters adjacent to the GOA when arrowtooth flounder, deep-water flatfish, and rex sole... authority of all eligible LLP licenses in the catcher/processor sector. (ii) For the deep-water halibut PSC...

78 FR 13161 - Fisheries of the Exclusive Economic Zone Off Alaska; Gulf of Alaska; Final 2013 and 2014 Harvest...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-26

... halibut PSC trawl limits between the trawl gear deep-water and the shallow-water species fishery... for pollock, sablefish, deep-water flatfish, rex sole, Pacific ocean perch, northern rockfish... less than the ABCs for Pacific cod, shallow-water flatfish, arrowtooth flounder, flathead sole, ``other...

Reduction of flatfish habitat as a consequence of the proliferation of an invasive mollusc

NASA Astrophysics Data System (ADS)

Kostecki, C.; Rochette, S.; Girardin, R.; Blanchard, M.; Desroy, N.; Le Pape, O.

2011-03-01

Coastal bays provide habitats for juveniles and adults of many marine species. Mont Saint-Michel Bay (MSMB, France) hosts a highly diversified fish community and constitutes one of the most important nursery grounds for many commercially exploited marine species, such as sea bass, flatfish, clupeids and rays in the English Channel. Besides, MSMB also suffers from the massive invasion of an exotic mollusc, the American slipper-limpet ( Crepidula fornicata, L.). This species arrived four decades ago and now represents the main filter-feeder biomass in the bay (150 Mt), an order of magnitude larger than local farmed and natural shellfishes. Recent analyses underlined the impact of this small gastropod on the trophic structure of this bay and its negative influence on juvenile sole densities in the nursery grounds. The present study uses a geostatistical approach to explore the effect of the extension of the slipper-limpet on flatfish (common sole Solea solea, L.; plaice Pleuronectes platessa, L.; brill Scophthalmus rhombus, L. and flounder Platichthys flesus, L.) spatial distribution. Data collected during survey of the MSMB at the end of the 1970s and three decades later have been used to build interpolated maps of (1) slipper-limpet and (2) flatfish spatial distributions. Slipper-limpets were concentrated in a small area, in the western part of the MSMB, in the 1970s while today they occupy half of the bay. This rapid proliferation led to the decrease of available surface for flatfishes, which previously occupied the whole bay and are now restricted to its eastern part. The present study highlighted that the negative influence on fish habitat in MSMB is apparently more related to changes in the substratum than to trophic interactions. This invasion has possible consequences on flatfish population renewal at a large scale and may also damage other benthic or demersal species, such as rays.

Move Over! Studying Flatfish Travel Patterns to Profile Fish Behavior

ERIC Educational Resources Information Center

Aultman, Terry; Curran, Mary Carla

2012-01-01

The way an animal moves from place to place can inform us about its life and environment. In this lesson, students examine the travel patterns of juvenile flatfishes in an estuary. The process of sampling bottom-dwelling fishes is explained, and data from a university-based marine science laboratory are evaluated. Students compare the distance…

50 CFR Table 2b to Part 660... - 2012, and beyond, Allocations by Species or Species Group (final 2012 allocations for assessed...

Code of Federal Regulations, 2011 CFR

2011-10-01

... or Species Group (final 2012 allocations for assessed flatfish are contingent upon potential changes to flatfish status determination criteria and the harvest control rule, and, for overfished species... Part 660, Subpart C—2012, and beyond, Allocations by Species or Species Group (final 2012 allocations...

76 FR 53840 - Fisheries of the Exclusive Economic Zone Off Alaska; Other Rockfish, Other Flatfish, Sharks, and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-30

..., Alaska Region, NMFS, has reviewed the most current available data and finds that the ITACs for AI other... CFR part 679. The 2011 initial total allowable catch (ITAC) of Aleutian Islands (AI) other rockfish... the AI other rockfish, BSAI other flatfish, BSAI sharks, and BSAI skates ITACs, respectively. This...

The influence of cage conditioning on the performance and behavior of Japanese flounder reared for stock enhancement: Burying, feeding, and threat response

NASA Astrophysics Data System (ADS)

Walsh, Michelle L.; Masuda, Reiji; Yamashita, Yoh

2014-01-01

Flatfish reared for stock enhancement often exhibit irregular behavioral patterns compared with wild conspecifics. These “deficits”, mostly attributed to the unnatural characteristics of the hatchery environment, are assumed to translate to increased predation risk. Initially releasing fish in predator-free conditioning cages may help flatfish adjust to the wild environment, establish burial skills, begin pigment change, recover from transport stress, and experience natural (live) food sources before full release into the wild. However, the impact of cage conditioning on the performance and behavior of flatfish has yet to be fully assessed. We conducted video trials with 10-cm, hatchery-reared Japanese flounder, Paralichthys olivaceus, in sand-bottomed aquaria to assess four treatments of flounder: (1) reared fish cage conditioned for 7 d in the shallow coast, (2) reared fish directly from hatchery tanks, (3) wild fish, and (4) reared fish released directly from hatchery tanks into the wild and then recaptured after 6 d at large. Burying ability, predation, and threat response to a model predator were examined. Wild fish buried most, followed by cage conditioned, and released-then-recaptured and non-conditioned (directly from tank) fish. Wild and conditioned fish revealed much lower variation in total movement duration, which corresponded with lower levels and variation in prey vertical movement. Fish of all condition types exhibited a lower number of attacks and off-bottom swimming events, and a lower movement duration when the model predator was in motion versus when it was still. This study is the first to evaluate the behavioral mechanisms of hatchery-reared flatfish that have been cage-conditioned or released-then-recaptured. In addition, we provide evidence that cage conditioning can enhance the performance of released flatfish.

Windowpane flounder (Scophthalmus aquosus) and winter flounder (Pseudopleuronectes americanus) responses to cold temperature extremes in a Northwest Atlantic estuary

NASA Astrophysics Data System (ADS)

Wilber, Dara H.; Clarke, Douglas G.; Alcoba, Catherine M.; Gallo, Jenine

2016-01-01

The effect of climate variability on flatfish includes not only the effects of warming on sensitive life history stages, but also impacts from more frequent or unseasonal extreme cold temperatures. Cold weather events can affect the overwintering capabilities of flatfish near their low temperature range limits. We examined the responses of two flatfish species, the thin-bodied windowpane (Scophthalmus aquosus) and cold-tolerant winter flounder (Pseudopleuronectes americanus), to variable winter temperatures in a Northwest Atlantic estuary using abundance and size data collected during a monitoring study, the Aquatic Biological Survey, conducted from 2002 to 2010. Winter and spring abundances of small (50 to 120 mm total length) juvenile windowpane were positively correlated with adult densities (spawning stock) and fall temperatures (thermal conditions experienced during post-settlement development for the fall-spawned cohort) of the previous year. Windowpane abundances in the estuary were significantly reduced and the smallest size class was nearly absent after several consecutive years with cold (minimum temperatures < 1 °C) winters. Interannual variation in winter flounder abundances was unrelated to the severity of winter temperatures. A Paulik diagram illustrates strong positive correlations between annual abundances of sequential winter flounder life history stages (egg, larval, Age-1 juvenile, and adult male) within the estuary, reflecting residency within the estuary through their first year of life. Temperature variables representing conditions during winter flounder larval and post-settlement development were not significant factors in multiple regression models exploring factors that affect juvenile abundances. Likewise, densities of predators known to consume winter flounder eggs and/or post-settlement juveniles were not significantly related to interannual variation in winter flounder juvenile abundances. Colder estuarine temperatures through the first year of life were associated with smaller Age-1 winter flounder body size. For example, Age-1 winter flounder developing under conditions that differed by 1.9 °C in mean daily water temperature, averaged 98.7 mm total length (TL) and 123.1 mm TL, for the relatively cold vs. moderate years, respectively. More frequent cold temperature extremes associated with climate variability may negatively impact the overwintering capabilities of some flatfish near their cold temperature range limits, whereas cold-tolerant species may experience reduced growth, which imparts the ecological challenges associated with smaller body size.

Distortion of frontal bones results from cell apoptosis by the mechanical force from the up-migrating eye during metamorphosis in Paralichthys olivaceus.

PubMed

Sun, Mingyan; Wei, Fen; Li, Hui; Xu, Juan; Chen, Xinye; Gong, Xiaoling; Tian, Yongsheng; Chen, Songlin; Bao, Baolong

2015-05-01

Craniofacial remodeling during flatfish metamorphosis, including eye migration, is perhaps the most striking example of asymmetric postembryonic development in the vertebrate world. The asymmetry of the cranium mainly results from distortion of the frontal bones, which depends on eye migration during metamorphosis. However, it is unclear how the up-migrating eye causes distortion of the frontal bones. In this study, we first show that distortion of the frontal bones during metamorphosis in Paralichthys olivaceus is the result of cell apoptosis, rather than cell autophagy or cell proliferation. Secondly, we report that cell apoptosis in the frontal bones is induced by the mechanical force transferred from the up-migrating eye. The mechanical force from the up-migrating eye signals through FAK to downstream molecules that are integrated into the BMP-2 signal pathway. Finally, it is shown that cell apoptosis in the frontal bones is activated by the intrinsic mitochondrial pathway; the extrinsic death receptor is not involved in this process. Moreover, cell apoptosis in frontal bones is not induced directly by thyroid hormones, which are thought to mediate metamorphosis in flatfishes and directly mediate cell apoptosis during amphibian metamorphosis. These findings help identify the major signaling route used during regulation of frontal bone distortion during metamorphosis in flatfish, and indicate that the asymmetry of the cranium, or at least the distortion of frontal bones, is the result of rather than the reason underlying eye migration. Copyright © 2015. Published by Elsevier Ireland Ltd.

Flatfish metamorphosis: a hypothalamic independent process?

PubMed

Campinho, Marco A; Silva, Nadia; Roman-Padilla, Javier; Ponce, Marian; Manchado, Manuel; Power, Deborah M

2015-03-15

Anuran and flatfish metamorphosis are tightly regulated by thyroid hormones that are the necessary and sufficient factors that drive this developmental event. In the present study whole mount in situ hybridization (WISH) and quantitative PCR in sole are used to explore the central regulation of flatfish metamorphosis. Central regulation of the thyroid in vertebrates is mediated by the hypothalamus-pituitary-thyroid (HPT) axis. Teleosts diverge from other vertebrates as hypothalamic regulation in the HPT axis is proposed to be through hypothalamic inhibition although the regulatory factor remains enigmatic. The dynamics of the HPT axis during sole metamorphosis revealed integration between the activity of the thyrotrophes in the pituitary and the thyroid follicles. No evidence was found supporting a role for thyroid releasing hormone (trh) or corticotrophin releasing hormone (crh) in hypothalamic control of TH production during sole metamorphosis. Intriguingly the results of the present study suggest that neither hypothalamic trh nor crh expression changes during sole metamorphosis and raises questions about the role of these factors and the hypothalamus in regulation of thyrotrophs. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Effects of oil spill related chemical pollution on helminth parasites in Mexican flounder Cyclopsetta chittendeni from the Campeche Sound, Gulf of Mexico.

PubMed

Centeno-Chalé, Oscar Arturo; Aguirre-Macedo, Ma Leopoldina; Gold-Bouchot, Gerardo; Vidal-Martínez, Víctor Manuel

2015-09-01

During an environmental impact study of an accidental oil spill in the Campeche Sound in October 2007, we examined the helminth parasites of the benthic flatfish Cyclopsetta chittendeni as well as the concentrations of hydrocarbons and heavy metals in the sediment. The aim of this study was to determine the potential effects of these contaminants on the helminth communities of the flatfish. A total of 427 hosts were examined, and 16,895 helminths, representing 17 species, were obtained from two surveys (March and July, 2008). Statistically significant negative associations were observed between the hydrocarbons and helminth parasite abundances using multivariate methods. The results suggest that in October 2007, the oil spill had a strong negative effect on these helminth communities. However, after five months, the impacted stations were re-populated by both the flatfish and helminths. The most likely explanation for this rapid recovery is the rescue effect from non-impacted habitats to impacted stations. Copyright © 2015 Elsevier Inc. All rights reserved.

A quantitative estimate of the function of soft-bottom sheltered coastal areas as essential flatfish nursery habitat

NASA Astrophysics Data System (ADS)

Trimoreau, E.; Archambault, B.; Brind'Amour, A.; Lepage, M.; Guitton, J.; Le Pape, O.

2013-11-01

Essential fish habitat suitability (EFHS) models and geographic information system (GIS) were combined to describe nursery habitats for three flatfish species (Solea solea, Pleuronectes platessa, Dicologlossa cuneata) in the Bay of Biscay (Western Europe), using physical parameters known or suspected to influence juvenile flatfish spatial distribution and density (i.e. bathymetry, sediment, estuarine influence and wave exposure). The effects of habitat features on juvenile distribution were first calculated from EFHS models, used to identify the habitats in which juvenile are concentrated. The EFHS model for S. solea confirmed previous findings regarding its preference for shallow soft bottom areas and provided new insights relating to the significant effect of wave exposure on nursery habitat suitability. The two other models extended these conclusions with some discrepancies among species related to their respective niches. Using a GIS, quantitative density maps were produced from EFHS models predictions. The respective areas of the different habitats were determined and their relative contributions (density × area) to the total amount of juveniles were calculated at the scale of stock management, in the Bay of Biscay. Shallow and muddy areas contributed to 70% of total juvenile relative abundance whereas only representing 16% of the coastal area, suggesting that they should be considered as essential habitats for these three flatfish species. For S. solea and P. platessa, wave exposure explained the propensity for sheltered areas, where concentration of juveniles was higher. Distribution maps of P. platessa and D. cuneata juveniles also revealed opposite spatial and temporal trends which were explained by the respective biogeographical distributions of these two species, close to their southern and northern limit respectively, and by their responses to hydroclimatic trends.

Hydrodynamic detection and localization of artificial flatfish breathing currents by harbour seals (Phoca vitulina).

PubMed

Niesterok, Benedikt; Krüger, Yvonne; Wieskotten, Sven; Dehnhardt, Guido; Hanke, Wolf

2017-01-15

Harbour seals are known to be opportunistic feeders, whose diet consists mainly of pelagic and benthic fish, such as flatfish. As flatfish are often cryptic and do not produce noise, we hypothesized that harbour seals are able to detect and localize flatfish using their hydrodynamic sensory system (vibrissae), as fish emit water currents through their gill openings (breathing currents). To test this hypothesis, we created an experimental platform where an artificial breathing current was emitted through one of eight different openings. Three seals were trained to search for the active opening and station there for 5 s. Half of the trials were conducted with the seal blindfolded with an eye mask. In blindfolded and non-blindfolded trials, all seals performed significantly better than chance. The seals crossed the artificial breathing current (being emitted into the water column at an angle of 45 deg to the ground) from different directions. There was no difference in performance when the seals approached from in front, from behind or from the side. All seals responded to the artificial breathing currents by directly moving their snout towards the opening from which the hydrodynamic stimulus was emitted. Thus, they were also able to extract directional information from the hydrodynamic stimulus. Hydrodynamic background noise and the swimming speed of the seals were also considered in this study as these are aggravating factors that seals in the wild have to face during foraging. By creating near-natural conditions, we show that harbour seals have the ability to detect a so-far overlooked type of stimulus. © 2017. Published by The Company of Biologists Ltd.

Oxidative Stress and Digestive Enzyme Activity of Flatfish Larvae in a Changing Ocean

PubMed Central

Pimentel, Marta S.; Faleiro, Filipa; Diniz, Mário; Machado, Jorge; Pousão-Ferreira, Pedro; Peck, Myron A.; Pörtner, Hans O.; Rosa, Rui

2015-01-01

Until now, it is not known how the antioxidant and digestive enzymatic machinery of fish early life stages will change with the combined effects of future ocean acidification and warming. Here we show that high pCO2 (~1600 μatm) significantly decreased metabolic rates (up to 27.4 %) of flatfish larvae, Solea senegalensis, at both present (18 °C) and warmer temperatures (+4 °C). Moreover, both warming and hypercapnia increased the heat shock response and the activity of antioxidant enzymes, namely catalase (CAT) and glutathione S-transferase (GST), mainly in post-metamorphic larvae (30 dph). The lack of changes in the activity of CAT and GST of pre-metamorphic larvae (10 dph) seems to indicate that earlier stages lack a fully-developed antioxidant defense system. Nevertheless, the heat shock and antioxidant responses of post-metamorphic larvae were not enough to avoid the peroxidative damage, which was greatly increased under future environmental conditions. Digestive enzymatic activity of S. senegalensis larvae was also affected by future predictions. Hypercapnic conditions led to a decrease in the activity of digestive enzymes, both pancreatic (up to 26.1 % for trypsin and 74.5 % for amylase) and intestinal enzymes (up to 36.1 % for alkaline phosphatase) in post-metamorphic larvae. Moreover, the impact of ocean acidification and warming on some of these physiological and biochemical variables (namely, lower OCR and higher HSP and MDA levels) were translated into larvae performance, being significantly correlated with decreased larval growth and survival or increased incidence of skeletal deformities. The increased vulnerability of flatfish early life stages under future ocean conditions is expected to potentially determine recruitment and population dynamics in marine ecosystems. PMID:26221723

Oxidative Stress and Digestive Enzyme Activity of Flatfish Larvae in a Changing Ocean.

PubMed

Pimentel, Marta S; Faleiro, Filipa; Diniz, Mário; Machado, Jorge; Pousão-Ferreira, Pedro; Peck, Myron A; Pörtner, Hans O; Rosa, Rui

2015-01-01

Until now, it is not known how the antioxidant and digestive enzymatic machinery of fish early life stages will change with the combined effects of future ocean acidification and warming. Here we show that high pCO2 (~1600 μatm) significantly decreased metabolic rates (up to 27.4 %) of flatfish larvae, Solea senegalensis, at both present (18 °C) and warmer temperatures (+4 °C). Moreover, both warming and hypercapnia increased the heat shock response and the activity of antioxidant enzymes, namely catalase (CAT) and glutathione S-transferase (GST), mainly in post-metamorphic larvae (30 dph). The lack of changes in the activity of CAT and GST of pre-metamorphic larvae (10 dph) seems to indicate that earlier stages lack a fully-developed antioxidant defense system. Nevertheless, the heat shock and antioxidant responses of post-metamorphic larvae were not enough to avoid the peroxidative damage, which was greatly increased under future environmental conditions. Digestive enzymatic activity of S. senegalensis larvae was also affected by future predictions. Hypercapnic conditions led to a decrease in the activity of digestive enzymes, both pancreatic (up to 26.1 % for trypsin and 74.5 % for amylase) and intestinal enzymes (up to 36.1 % for alkaline phosphatase) in post-metamorphic larvae. Moreover, the impact of ocean acidification and warming on some of these physiological and biochemical variables (namely, lower OCR and higher HSP and MDA levels) were translated into larvae performance, being significantly correlated with decreased larval growth and survival or increased incidence of skeletal deformities. The increased vulnerability of flatfish early life stages under future ocean conditions is expected to potentially determine recruitment and population dynamics in marine ecosystems.

Quantification of bupivacaine hydrochloride and isoflupredone acetate residues in porcine muscle, beef, milk, egg, shrimp, flatfish, and eel using a simplified extraction method coupled with liquid chromatography-triple quadrupole tandem mass spectrometry.

PubMed

Cho, Sang-Hyun; Park, Jin-A; Zheng, Weijia; Abd El-Aty, A M; Kim, Seong-Kwan; Choi, Jeong-Min; Yi, Hee; Cho, Soo-Min; Afifi, Nehal A; Shim, Jae-Han; Chang, Byung-Joon; Kim, Jin-Suk; Shin, Ho-Chul

2017-10-15

In this study, a simple analytical approach has been developed and validated for the determination of bupivacaine hydrochloride and isoflupredone acetate residues in porcine muscle, beef, milk, egg, shrimp, flatfish, and eel using liquid chromatography-tandem mass spectrometry (LC-MS/MS). A 0.1% solution of acetic acid in acetonitrile combined with n-hexane was used for deproteinization and defatting of all tested matrices and the target drugs were well separated on a Waters Xbridge™ C18 analytical column using a mobile phase consisting of 0.1% acetic acid (A) and 0.1% solution of acetic acid in methanol (B). The linearity estimated from six-point matrix-matched calibrations was good, with coefficients of determination ≥0.9873. The limits of quantification (LOQs) for bupivacaine hydrochloride and isoflupredone acetate were 1 and 2ngg -1 , respectively. Recovery percentages in the ranges of 72.51-112.39% (bupivacaine hydrochloride) and 72.58-114.56% (isoflupredone acetate) were obtained from three different fortification concentrations with relative standard deviations (RSDs) of <15.14%. All samples for the experimental work and method application were collected from the local markets in Seoul, Republic of Korea, and none of them tested positive for the target drugs. In conclusion, a simple method using a 0.1% solution of acetic acid in acetonitrile and n-hexane followed by LC-MS/MS could effectively extract bupivacaine hydrochloride and isoflupredone acetate from porcine muscle, beef, milk, egg, shrimp, flatfish, and eel samples. Copyright © 2017 Elsevier B.V. All rights reserved.

Whole genome sequencing of turbot (Scophthalmus maximus; Pleuronectiformes): a fish adapted to demersal life

PubMed Central

Figueras, Antonio; Robledo, Diego; Corvelo, André; Hermida, Miguel; Pereiro, Patricia; Rubiolo, Juan A.; Gómez-Garrido, Jèssica; Carreté, Laia; Bello, Xabier; Gut, Marta; Gut, Ivo Glynne; Marcet-Houben, Marina; Forn-Cuní, Gabriel; Galán, Beatriz; García, José Luis; Abal-Fabeiro, José Luis; Pardo, Belen G.; Taboada, Xoana; Fernández, Carlos; Vlasova, Anna; Hermoso-Pulido, Antonio; Guigó, Roderic; Álvarez-Dios, José Antonio; Gómez-Tato, Antonio; Viñas, Ana; Maside, Xulio; Gabaldón, Toni; Novoa, Beatriz; Bouza, Carmen; Alioto, Tyler; Martínez, Paulino

2016-01-01

The turbot is a flatfish (Pleuronectiformes) with increasing commercial value, which has prompted active genomic research aimed at more efficient selection. Here we present the sequence and annotation of the turbot genome, which represents a milestone for both boosting breeding programmes and ascertaining the origin and diversification of flatfish. We compare the turbot genome with model fish genomes to investigate teleost chromosome evolution. We observe a conserved macrosyntenic pattern within Percomorpha and identify large syntenic blocks within the turbot genome related to the teleost genome duplication. We identify gene family expansions and positive selection of genes associated with vision and metabolism of membrane lipids, which suggests adaptation to demersal lifestyle and to cold temperatures, respectively. Our data indicate a quick evolution and diversification of flatfish to adapt to benthic life and provide clues for understanding their controversial origin. Moreover, we investigate the genomic architecture of growth, sex determination and disease resistance, key traits for understanding local adaptation and boosting turbot production, by mapping candidate genes and previously reported quantitative trait loci. The genomic architecture of these productive traits has allowed the identification of candidate genes and enriched pathways that may represent useful information for future marker-assisted selection in turbot. PMID:26951068

Whole genome sequencing of turbot (Scophthalmus maximus; Pleuronectiformes): a fish adapted to demersal life.

PubMed

Figueras, Antonio; Robledo, Diego; Corvelo, André; Hermida, Miguel; Pereiro, Patricia; Rubiolo, Juan A; Gómez-Garrido, Jèssica; Carreté, Laia; Bello, Xabier; Gut, Marta; Gut, Ivo Glynne; Marcet-Houben, Marina; Forn-Cuní, Gabriel; Galán, Beatriz; García, José Luis; Abal-Fabeiro, José Luis; Pardo, Belen G; Taboada, Xoana; Fernández, Carlos; Vlasova, Anna; Hermoso-Pulido, Antonio; Guigó, Roderic; Álvarez-Dios, José Antonio; Gómez-Tato, Antonio; Viñas, Ana; Maside, Xulio; Gabaldón, Toni; Novoa, Beatriz; Bouza, Carmen; Alioto, Tyler; Martínez, Paulino

2016-06-01

The turbot is a flatfish (Pleuronectiformes) with increasing commercial value, which has prompted active genomic research aimed at more efficient selection. Here we present the sequence and annotation of the turbot genome, which represents a milestone for both boosting breeding programmes and ascertaining the origin and diversification of flatfish. We compare the turbot genome with model fish genomes to investigate teleost chromosome evolution. We observe a conserved macrosyntenic pattern within Percomorpha and identify large syntenic blocks within the turbot genome related to the teleost genome duplication. We identify gene family expansions and positive selection of genes associated with vision and metabolism of membrane lipids, which suggests adaptation to demersal lifestyle and to cold temperatures, respectively. Our data indicate a quick evolution and diversification of flatfish to adapt to benthic life and provide clues for understanding their controversial origin. Moreover, we investigate the genomic architecture of growth, sex determination and disease resistance, key traits for understanding local adaptation and boosting turbot production, by mapping candidate genes and previously reported quantitative trait loci. The genomic architecture of these productive traits has allowed the identification of candidate genes and enriched pathways that may represent useful information for future marker-assisted selection in turbot. © The Author 2016. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.

Colonization and nursery habitat use patterns of larval and juvenile flatfish species in a small temperate estuary

NASA Astrophysics Data System (ADS)

Primo, Ana Lígia; Azeiteiro, Ulisses M.; Marques, Sónia C.; Martinho, Filipe; Baptista, Joana; Pardal, Miguel A.

2013-02-01

Migrations between coastal and estuarine nursery areas are essential for successful completion of the life cycle of several marine fish. The present study evaluates the use of a small temperate estuary, the Mondego, Portugal, as a nursery habitat for several flatfishes during their early life stages. Data from seasonal and diel larval sampling at the mouth of the estuary and both larvae and juvenile monthly spatial distribution in the estuary (2005-2009) were gathered in order to investigate the life cycle of Platichthys flesus, Solea solea and Solea senegalensis. Larvae entrance in the estuary occurred mainly during summer and autumn with no evidence for diel or tidal vertical stratification. S. senegalensis larvae were present in all seasons at downstream areas presenting low successful settlement and juveniles' densities inside the estuary. Conversely, P. flesus and S. solea were mainly present as juveniles with upstream areas being preferred by flounder. Both species larvae seemed to settle in nearby coastal areas. The importance of the Mondego estuary for flatfishes differed according to the species, playing an important role mainly during the first year for all species. The present study highlights the importance of integrating larval and juvenile stages of fish to assess the very important role of estuaries as nursery areas.

[Mercury concentration of fish in Tokyo Bay and the surrounding sea area].

PubMed

Zhang, R; Kashima, Y; Matsui, M; Okabe, T; Doi, R

2001-07-01

Total mercury in the muscles of three fish species was analyzed in fish caught in Tokyo Bay and the surrounding sea areas, Sagami Bay and Choshi. Tokyo Bay is a semi-closed sea area surrounded by Tokyo, Kanagawa and Chiba prefectures. Sagami Bay and Choshi are open to the Pacific Ocean. A total of 412 fish consisting of northern whiting (Sillago japonica), flatfish (Limanda yokohamae) and sardine (Sardinops melanosticta) were caught in these areas over a 6 months period from November 1998 to April 1999. Total mercury concentration ranged from 0.008-0.092 microgram/g (wet wt.) in northern whiting, 0.006-0.065 microgram/g in flatfish and 0.001-0.045 microgram/g in sardine. All concentrations were below the restriction limit of fish mercury in Japan, 0.4 microgram/g of total mercury concentration. A significant correlation was found between mercury concentrations and body length or body weight in northern whiting and flatfish, irrespective of the sea area. A correlation was also found between mercury concentration in fish and their feeding habits: among the 3 species caught in the same area, crustacean feeding northern whiting had the highest, polychaete feeding flatfish moderate, and plankton feeding sardine had the lowest mercury concentration. In a comparison of mercury concentration in the same species caught in different sea areas, a higher concentration was noted in fish caught in the semi-closed sea area of Tokyo Bay, than in fish caught in the open sea areas of Sagami Bay and Choshi. This difference was most marked in fish caught at the bottom of Tokyo Bay and we considered that the mercury concentration of seawater and sediment in these areas was the cause of mercury accumulation in fish. These findings suggest that improved water quality control and environmental monitoring is necessary in semi-closed sea areas such as Tokyo Bay.

Population-regulating processes during the adult phase in flatfish

NASA Astrophysics Data System (ADS)

Rijnsdorp, A. D.

Flatfish support major fisheries and the study of regulatory processes are of paramount importance for evaluating the resilience of the resource to exploitation. This paper reviews the evidence for processes operating during the adult phase that may 1. generate interannual variability in recruitment; 2. contribute to population regulation through density-dependent growth, density-dependent ripening of adults and density-dependent egg production. With regard to (1), there is evidence that in the adult phase processes do occur that may generate recruitment variability through variation in size-specific fecundity, contraction of spawning season, reduction in egg quality, change in sex ratio and size composition of the adult population. However, time series of recruitment do not provide support for this hypothesis. With regard to (2), there is ample evidence that exploitation of flatfish coincides with an increase in growth, although the mechanisms involved are not always clear. The presence of density-dependent growth in the adult phase of unexploited populations appears to be the most likely explanation in some cases. From the early years of exploitation of flatfish stocks inhabiting cold waters, evidence exists that adult fish do not spawn each year. Fecundity schedules show annual variations, but the available information suggests that size-specific fecundity is stable over a broad range of population abundance and may only decrease at high population abundance. The analysis is complicated by the possibility of a trade-off between egg numbers and egg size. Nevertheless, a density-dependent decrease in growth will automatically result in a decrease in absolute fecundity because of the reduced body size. The potential contribution of these regulatory effects on population regulation is explored. Results indicate that density-dependent ripening and absolute fecundity, mediated through density-dependent growth, may control recruitment at high levels of population abundance. The effect of a density-dependent decrease in size-specific fecundity seems to play a minor role, although this role may become important at extremely high levels of population abundance.

Stable isotope evidence of terrestrial organic matter incorporation into coastal marine food webs: impact of Rhone River inputs on five NW Mediterranean marine flatfish species.

NASA Astrophysics Data System (ADS)

Darnaude, A. M.; Salen-Picard, C.; Harmelin-Vivien, M.

2003-04-01

The positive influence of land-based run-off on coastal fishery production is thought to be of particular importance for oligotrophic seas such as the Mediterranean. In order to estimate the impact of the Rhone River inputs of particulate organic matter (POM) on exploited demersal fish populations, stable isotope signature in nitrogen (δ15N) and carbon (δ13C) were determined for both juveniles and adults of the five main flatfish species living off the Rhone delta (Arnoglossus laterna, Buglossidium luteum, Citharus linguatula, Solea impar and Solea solea) and the main components of their food webs. The five flatfish species showed inter and intra-specific differences in isotopic signatures. The δ15N significantly increased from the smallest species to the largest ones and, in all species, from juveniles to adults (P<0.05), which indicated a global increase in trophic level with fish body size. Concerning the carbon signature, the δ13C obtained indicated an incorporation of organic material from terrestrial origin in the flesh of all the species. This incorporation was minimum for C. linguatula and reduced for all the species with the exception of S. solea for which a significantly (P<0.001) lower δ13C indicated an important use of organic matter from terrestrial origin. Mean δ13C values also differed significantly between juveniles and adults of B. luteum and S. impar (P<0.05), suggesting changes in terrestrial organic matter use with growth in these two species. To explain inter and intra-specific differences in δ13C, stable isotope data were compared with gut content analyses (prey % total contents mass, W%) performed on the same fishes. The δ13C signature of fishes was inversely related to the W% of polychaetes in their diet, and not to other prey categories. The common sole S. solea, that fed mainly on polychaetes (W% > 50% at all benthic stages of life), exhibited the most negative mean δ13C for both juveniles and adults among all the fish species studied. The isotopic analyses of the Rhone River water, the marine phytoplankton, the sediment and the main fish prey, confirmed that polychaetes represented the major pathway of terrestrial POM transfer up to fishes into coastal trophic webs. The effect of terrestrial inputs in enhancing the population dynamics of the five flatfish species studied differed thus according to their diet. Keywords : river run-off, food webs, stable isotopes, gut contents, flatfishes, fisheries, NW Mediterranean.

Heteroplasmy and evidence for recombination in the mitochondrial control region of the flatfish Platichthys flesus.

PubMed

Hoarau, Galice; Holla, Suzanne; Lescasse, Rachel; Stam, Wytze T; Olsen, Jeanine L

2002-12-01

The general assumption that mitochondrial DNA (mtDNA) does not undergo recombination has been challenged recently in invertebrates. Here we present the first direct evidence for recombination in the mtDNA of a vertebrate, the flounder Platichthys flesus. The control region in the mtDNA of this flatfish is characterized by the presence of a variable number of tandem repeats and a high level of heteroplasmy. Two types of repeats were recognized, differing by two C-T point mutations. Most individuals carry a pure "C" or a pure "T" array, but one individual showed a compound "CT" array. Such a compound array is evidence for recombination in the mtDNA control region from the flounder.

Temperature induced changes in size dependent distributions of two boreal and three Lusitanian flatfish species: A comparative study

NASA Astrophysics Data System (ADS)

van Hal, Ralf; van Kooten, Tobias; Rijnsdorp, Adriaan D.

2016-01-01

Changes in spatial distribution in several fish species have been related to recent increase in global temperature. In the North Sea, both a poleward shift and a shift to deeper water have been observed. Here, we study the underlying mechanism of these shifts in a comparative study of the changes in distribution of two boreal flatfish species (plaice Pleuronectes platessa and dab Limanda limanda) and three Lusitanian flatfish species (sole Solea solea, solenette Buglossidium luteum, and scaldfish Arnoglossus laterna) as recorded in annual bottom trawl surveys carried out in the North Sea in late summer since 1985. The distribution is analysed in relation to the bottom temperature at the time of the survey as well as to the seasonal maximum bottom temperature earlier in the year. It is shown that the boreal species plaice and dab moved to deeper water and maintained the seasonal maximum temperature that they experienced in earlier periods, while the Lusitanian species sole, solenette, and scaldfish experienced an increase in the seasonal maximum temperature that they experienced while maintaining their depth distribution. This overall response varied between length classes, reflecting a preference for higher temperature of the smaller length classes. The results lend support to the hypothesis that the fish displayed a direct response to the maximum temperature that occurred during the growth season before the time of sampling.

Fillet proximate composition, lipid quality, yields, and organoleptic quality of Mediterranean-farmed marine fish: A review with emphasis on new species.

PubMed

Grigorakis, Kriton

2017-09-22

Species diversification in Mediterranean mariculture involves various important fish that contribute to the diet of many human populations. These include meagres (Sciaenidae), flatfishes, mullets, and various sparids. Their quality aspects (yields, fillet proximate composition, and lipid quality) are discussed in this review. Their filleting yield is mostly 40-45%. The viscerosomatic index ranges from 1.5% to 14%, depending on species. Low muscle fat contents of flatfishes and meagres differentiate them from the rest of the farmed species. Farmed fish contain high n-3 polyunsaturates fatty acids (PUFA; 12.3-36.3% vs. 5.48-37.2% in the wild) and have higher muscle fat and n-6 PUFA contents (mainly 18:2 n-6) than their wild counterparts. The aquaculture management, diet, and season can affect fillet composition and fatty acids, while season (i.e. food availability and maturation) largely affects lipid quality in wild fish. Data on the sensory quality of Mediterranean-farmed species are mainly limited to whether specific management differentiates the sensory quality; thus, further development of tools for sensory analysis is required. Observations on the quality features in farmed Mediterranean fish indicate that species diversification can also provide product diversification based on different commercial weights and fillet quality specifications.

A New Paradigm for Ovarian Sex Cord-Stromal Tumor Development

DTIC Science & Technology

2016-05-01

1 AWARD NUMBER: W81XWH-15-1-0082 TITLE: A New Paradigm for Ovarian Sex Cord-Stromal Tumor Development PRINCIPAL INVESTIGATOR: Qinglei Li...5a. CONTRACT NUMBER A New Paradigm for Ovarian Sex Cord-Stromal Tumor Development 5b. GRANT NUMBER W81XWH-15-1-0082 5c. PROGRAM ELEMENT NUMBER 6...role of sustained activation of oocyte TGFBR1 in ovarian tumor development using an in vitro approach. 2. Keywords Ovarian tumor, Sex cord

75 FR 67032 - Fisheries Off West Coast States; Pacific Coast Groundfish Fishery Management Plan; Amendments 20...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-01

... flounder, other flatfish, and slope rockfish. Increases are necessary to relieve a restriction by allowing... round fishing opportunities to provide community stability. These corrections are needed to keep the...

Potential applications of immunoassays in studies of flatfish recruitment

NASA Astrophysics Data System (ADS)

Feller, Robert J.

The fisheries recruitment-stock problem, a lack of correlation between measures of reproductive output of the parent stock and recruitment to the fishery, has several potential biotic and abiotic causes. Immunoassays may be useful in examining several aspects of this and several other problems in flatfish ecology: stock identification, parasitism and disease, and trophic interactions. Given stage-specific antisera capable of recognozing antigenic moieties of, for instance, eggs, larvae, or newly-settled juveniles, it is possible to screen stomach contents of many putative predators ( e.g., shrimp or crabs) rapidly for the presence and amounts of platfish prey. This trophic application of immunological methods has great promise for measuring loss of potential recruits to predation. All immunoassays are limited by the quality of antisera used and the researcher's ability to interpret quantitative data in an ecologically meaningful way. Key references for applications of immunoassays in fish-related questions are provided with recommendations for their utilization.

The latest animal models of ovarian cancer for novel drug discovery.

PubMed

Magnotti, Elizabeth; Marasco, Wayne A

2018-03-01

Epithelial ovarian cancer is a heterogeneous disease classified into five subtypes, each with a different molecular profile. Most cases of ovarian cancer are diagnosed after metastasis of the primary tumor and are resistant to traditional platinum-based chemotherapeutics. Mouse models of ovarian cancer have been utilized to discern ovarian cancer tumorigenesis and the tumor's response to therapeutics. Areas covered: The authors provide a review of mouse models currently employed to understand ovarian cancer. This article focuses on advances in the development of orthotopic and patient-derived tumor xenograft (PDX) mouse models of ovarian cancer and discusses current humanized mouse models of ovarian cancer. Expert opinion: The authors suggest that humanized mouse models of ovarian cancer will provide new insight into the role of the human immune system in combating and augmenting ovarian cancer and aid in the development of novel therapeutics. Development of humanized mouse models will take advantage of the NSG and NSG-SGM3 strains of mice as well as new strains that are actively being derived.

Updated analysis of flatfish recruitment response to climate variability and ocean conditions in the Eastern Bering Sea

NASA Astrophysics Data System (ADS)

Wilderbuer, Thomas; Stockhausen, William; Bond, Nicholas

2013-10-01

This study provides a retrospective analysis of the relationship between physical oceanography, biology and recruitment of three Eastern Bering Sea flatfish stocks: flathead sole (Hippoglossoides elassodon), northern rock sole (Lepidopsetta polyxystra), and arrowtooth flounder (Atheresthes stomias) during the period 1978-2005. Stock assessment model estimates of recruitment and spawning stock size indicate that temporal patterns in productivity are consistent with decadal scale (or shorter) patterns in climate variability, which may influence marine survival during the early life history phases. Density-dependence (through spawning stock size) was statistically significant in a Ricker stock-recruit model of flatfish recruitment that included environmental terms. Wind-driven advection of northern rock sole and flathead sole larvae to favorable nursery grounds was found to coincide with years of above-average recruitment. Ocean forcing of Bristol Bay surface waters during springtime was mostly on-shelf (eastward) during the 1980s and again in the early 2000s, but was off-shelf (westerly) during the 1990s, corresponding with periods of good and poor recruitment, respectively. Finally, the Arctic Oscillation was found to be an important indicator of arrowtooth flounder productivity. Model results were applied to IPCC (Intergovernmental Panel on Climate Change) future springtime wind scenarios to predict the future impact of climate on northern rock sole productivity and indicated that a moderate future increase in recruitment might be expected because the climate trends favor on-shelf transport but that density-dependence will dampen this effect such that northern rock sole abundance will not be substantially affected by climate change.

MORPHOMETRIC EVIDENCE FOR NUTRITIONAL STRESS IN ENGLISH SOLE

EPA Science Inventory

We present an application of the powerful thin plate spline method of morphometric analysis to demonstrate its utility for detecting environmental stress in an estuarine flatfish. Juvenile English sole (Pleuronectes vetulus) were captured from Yaquina Bay, Oregon, photographed w...

Prevalence and Risk Factors of Ovarian Metastases in Breast Cancer Patients < 41 Years of Age in the Netherlands: A Nationwide Retrospective Cohort Study.

PubMed

Peters, Inge T A; van Zwet, Erik W; Smit, Vincent T H B M; Liefers, Gerrit Jan; Kuppen, Peter J K; Hilders, Carina G J M; Trimbos, J Baptist

2017-01-01

Breast cancer is one of the primary indications for cryopreservation and subsequent autotransplantation of ovarian tissue. The safety of this fertility preservation method remains questionable, as the presence of disseminated breast tumor cells cannot yet be excluded in the ovarian autografts. We explored the prevalence of ovarian metastases among young breast cancer patients and determined risk factors for the development of ovarian metastases. Using the nationwide database of the Dutch Pathology Registry (PALGA), we identified a cohort of 2648 women with primary invasive breast cancer at age < 41 years in the period 2000-2010 in the Netherlands who subsequently underwent an oophorectomy. From this source population, all cases who had histologically confirmed ovarian metastases were included. For each case of whom clinical data were available, one control without ovarian metastases who matched the time interval between breast cancer diagnosis and oophorectomy was selected. Data were collected on patient characteristics, diagnosis, treatment and follow-up. Ovarian metastases were found in 63 out of 2648 patients who met the inclusion criteria. The risk of developing ovarian metastases increased with time passed since breast cancer diagnosis. Multivariate logistic regression analyses showed significant association between tumor stage and the development of ovarian metastases (p = 0.024). The prevalence of ovarian metastases was 2.4% among young breast cancer patients. Early ovary removal may reduce the risk of developing ovarian metastases. In breast cancer patients with tumors > 5 cm and/or inflammatory carcinoma, we recommend a cautious approach to ovarian tissue autotransplantation.

Identification, characterization and functional analysis of regulatory region of nanos gene from half-smooth tongue sole (Cynoglossus semilaevis).

PubMed

Huang, Jinqiang; Li, Yongjuan; Shao, Changwei; Wang, Na; Chen, Songlin

2017-06-20

The nanos gene encodes an RNA-binding zinc finger protein, which is required in the development and maintenance of germ cells. However, there is very limited information about nanos in flatfish, which impedes its application in fish breeding. In this study, we report the molecular cloning, characterization and functional analysis of the 3'-untranslated region of the nanos gene (Csnanos) from half-smooth tongue sole (Cynoglossus semilaevis), which is an economically important flatfish in China. The 1233-bp cDNA sequence, 1709-bp genomic sequence and flanking sequences (2.8-kb 5'- and 1.6-kb 3'-flanking regions) of Csnanos were cloned and characterized. Sequence analysis revealed that CsNanos shares low homology with Nanos in other species, but the zinc finger domain of CsNanos is highly similar. Phylogenetic analysis indicated that CsNanos belongs to the Nanos2 subfamily. Csnanos expression was widely detected in various tissues, but the expression level was higher in testis and ovary. During early development and sex differentiation, Csnanos expression exhibited a clear sexually dimorphic pattern, suggesting its different roles in the migration and differentiation of primordial germ cells (PGCs). Higher expression levels of Csnanos mRNA in normal females and males than in neomales indicated that the nanos gene may play key roles in maintaining the differentiation of gonad. Moreover, medaka PGCs were successfully labeled by the microinjection of synthesized mRNA consisting of green fluorescence protein and the 3'-untranslated region of Csnanos. These findings provide new insights into nanos gene expression and function, and lay the foundation for further study of PGC development and applications in tongue sole breeding. Copyright © 2017 Elsevier B.V. All rights reserved.

Germ-line activation of the luteinizing hormone receptor directly drives spermiogenesis in a nonmammalian vertebrate

PubMed Central

Chauvigné, François; Zapater, Cinta; Gasol, Josep M.; Cerdà, Joan

2014-01-01

In both mammals and teleosts, the differentiation of postmeiotic spermatids to spermatozoa (spermiogenesis) is thought to be indirectly controlled by the luteinizing hormone (LH) acting through the LH/choriogonadotropin receptor (LHCGR) to stimulate androgen secretion in the interstitial Leydig cells. However, a more direct, nonsteroidal role of LH mediating the spermiogenic pathway remains unclear. Using a flatfish with semicystic spermatogenesis, in which spermatids are released into the seminiferous lobule lumen (SLL), where they develop into spermatozoa without direct contact with the supporting Sertoli cells, we show that haploid spermatids express the homolog of the tetrapod LHCGR (Lhcgrba). Both native Lh and intramuscularly injected His-tagged recombinant Lh (rLh) are immunodetected bound to the Lhcgrba of free spermatids in the SLL, showing that circulating gonadotropin can reach the intratubular compartment. In vitro incubation of flatfish spermatids isolated from the SLL with rLh specifically promotes their differentiation into spermatozoa, whereas recombinant follicle-stimulating hormone and steroid hormones are ineffective. Using a repertoire of molecular markers and inhibitors, we find that the Lh-Lhcgrba induction of spermiogenesis is mediated through a cAMP/PKA signaling pathway that initiates the transcription of genes potentially involved in the function of spermatozoa. We further show that Lhcgrba expression in germ cells also occurs in distantly related fishes, suggesting this feature is likely conserved in teleosts regardless of the type of germ cell development. These data reveal a role of LH in vertebrate germ cells, whereby a Lhcgrba-activated signaling cascade in haploid spermatids directs gene expression and the progression of spermiogenesis. PMID:24474769

Comparative sequence analysis of the complete set of 40S ribosomal proteins in the Senegalese sole (Solea senegalensis Kaup) and Atlantic halibut (Hippoglossus hippoglossus L.) (Teleostei: Pleuronectiformes): phylogeny and tissue- and development-specific expression.

PubMed

Manchado, Manuel; Infante, Carlos; Asensio, Esther; Cañavate, Jose Pedro; Douglas, Susan E

2007-07-03

Ribosomal proteins (RPs) are key components of ribosomes, the cellular organelle responsible for protein biosynthesis in cells. Their levels can vary as a function of organism growth and development; however, some RPs have been associated with other cellular processes or extraribosomal functions. Their high representation in cDNA libraries has resulted in the increase of RP sequences available from different organisms and their proposal as appropriate molecular markers for phylogenetic analysis. The development of large-scale genomics of Senegalese sole (Solea senegalensis) and Atlantic halibut (Hippoglossus hippoglossus), two commercially important flatfish species, has made possible the identification and systematic analysis of the complete set of RP sequences for the small (40S) ribosome subunit. Amino acid sequence comparisons showed a high similarity both between these two flatfish species and with respect to other fish and human. EST analysis revealed the existence of two and four RPS27 genes in Senegalese sole and Atlantic halibut, respectively. Phylogenetic analysis clustered RPS27 in two separate clades with their fish and mammalian counterparts. Steady-state transcript levels for eight RPs (RPS2, RPS3a, RPS15, RPS27-1, RPS27-2, RPS27a, RPS28, and RPS29) in sole were quantitated during larval development and in tissues, using a real-time PCR approach. All eight RPs exhibited different expression patterns in tissues with the lowest levels in brain. On the contrary, RP transcripts increased co-ordinately after first larval feeding reducing progressively during the metamorphic process. The genomic resources and knowledge developed in this survey will provide new insights into the evolution of Pleuronectiformes. Expression data will contribute to a better understanding of RP functions in fish, especially the mechanisms that govern growth and development in larvae, with implications in aquaculture.

Dietary aspirin decreases the stage of ovarian cancer in the hen.

PubMed

Urick, M E; Giles, J R; Johnson, P A

2009-01-01

We aimed to determine the effects of dietary aspirin treatment on ovarian cancer incidence and progression in the hen as a model for the human disease. Hens were fed a standard layer diet (control) or the same diet containing 0.1% aspirin for 1 year. Liver prostaglandin E(2) (PGE(2)) was measured using an enzyme immunoassay. Incidence and stage of ovarian cancer were determined through necropsy and immunohistochemical analysis of ovarian sections for each hen. Aspirin treatment decreased liver PGE(2) in treated hens as compared to control hens. Treatment with aspirin did not decrease ovarian cancer incidence. Significantly more control hens developed late stage ovarian cancer than early stage, while the same was not true for aspirin-treated hens. Hens that developed ovarian cancer, even early ovarian cancer, produced significantly fewer eggs in the year prior to diagnosis than hens without ovarian cancer. Aspirin treatment may inhibit the progression of ovarian cancer in the hen and egg production may be used to identify hens with early stages of the disease.

Risk factors and the economic impact of ovarian cysts on reproductive performance of dairy cows in Korea.

PubMed

Kim, Ki-Doek; Ki, Kwang-Sook; Kang, Hyun-Gu; Kim, Ill-Hwa

2005-08-01

The objectives of this study were to determine the risk factors for development of postpartum ovarian cysts by evaluating several reproductive factors in individual cows, and to determine the economic impact of ovarian cysts on subsequent reproductive performance in dairy herds in Korea. The data, including cow parity, abnormal puerperium, endometritis, body condition score (BCS), and breeding status were collected from 634 cows in 9 dairy herds. We used logistic regression to evaluate the effects of these factors on ovarian cysts. A stepwise procedure, used to obtain the appropriate model with alpha=0.05, revealed that cow parity was the most important risk factor for ovarian cyst development within 8 weeks postpartum, while development of endometritis and BCS loss>or=1 from the dry period to 8 weeks postpartum were the most important risk factors for ovarian cyst development beyond 8 weeks postpartum. The occurrence of ovarian cysts beyond 8 weeks postpartum prolonged (P<0.01) the mean intervals from calving to first service (27 days) and conception (77 days), and increased (P<0.05) the culling rate (7.8%), while ovarian cyst development within 8 weeks postpartum did not affect (P>0.05) the mean intervals from calving to first service and conception or the culling rate. The economic loss resulting from the occurrence of ovarian cysts was estimated at approximately 823,996 won ($687) due to effects on the cost of nutrition, average growth of calves, labor and medical costs, and culling. These results suggest that cow parity is correlated with the development of ovarian cysts within 8 weeks postpartum, and endometritis and BCS loss>or=1 from the dry period to 8 weeks postpartum are correlated with the development of ovarian cysts after 8 weeks postpartum, which decreases reproductive performance and results in economic loss in dairy herds in Korea.

[Peripubertal ovarian cyst torsion as an early complication of undiagnosed polycystic ovarian syndrome].

PubMed

Ságodi, László; Schmidt, Ildikó; Vámosi, Ildikó; Barkai, László

2013-01-20

The aim of the authors is to present two cases which raise the possibility of an association between polycystic ovarian syndrome/hyperandrogenism and ovarian cyst torsion in peripubertal girls. Androgen excess may cause more frequently ovarian cyst formation in premenarcheal or young adolescents with undiagnosed polycystic ovarian syndrome than in adults. The authors recommend that polycystic ovarian syndrome as well as late onset congenital adrenal hyperplasia should be considered in peripubertal adolescents with ovarian cyst torsion. In case polycystic ovarian syndrome is confirmed, adequate management according to age and pubertal development of the patients should be commenced.

50 CFR Figure 1 to Subpart G of... - Diagram of Selective Flatfish Trawl

Code of Federal Regulations, 2010 CFR

2010-10-01

... Figure 1 to Subpart G of Part 660 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL.... § 660.360 Recreational fishery-management measures. (a) General. Federal recreational groundfish... recreational “other flatfish” fishery). (c) State-specific recreational fishery management measures. Federal...

Examination of diagnostic features in multiphoton microscopy and optical coherence tomography images of ovarian tumorigenesis in a mouse model

NASA Astrophysics Data System (ADS)

Watson, Jennifer M.

Ovarian cancer is a deadly disease owing to the non-specific symptoms and suspected rapid progression, leading to frequent late stage detection and poor prognosis. Medical imaging methods such as CT, MRI and ultrasound as well as serum testing for cancer markers have had extremely poor performance for early disease detection. Due to the poor performance of available screening methods, and the impracticality and ineffectiveness of taking tissue biopsies from the ovary, women at high risk for developing ovarian cancer are often advised to undergo prophylactic salpingo-oophorectomy. This surgery results in many side effects and is most often unnecessary since only a fraction of high risk women go on to develop ovarian cancer. Better understanding of the early development of ovarian cancer and characterization of morphological changes associated with early disease could lead to the development of an effective screening test for women at high risk. Optical imaging methods including optical coherence tomography (OCT) and multiphoton microscopy (MPM) are excellent tools for studying disease progression owing to the high resolution and depth sectioning capabilities. Further, these techniques are excellent for optical biopsy because they can image in situ non-destructively. In the studies described in this dissertation OCT and MPM are used to identify cellular and tissue morphological changes associated with early tumor development in a mouse model of ovarian cancer. This work is organized into three specific aims. The first aim is to use the images from the MPM phenomenon of second harmonic generation to quantitatively examine the morphological differences in collagen structure in normal mouse ovarian tissue and mouse ovarian tumors. The second aim is to examine the differences in endogenous two-photon excited fluorescence in normal mouse ovarian tissue and mouse ovarian tumors. The third and final aim is to identify changes in ovarian microstructure resulting from early disease development by imaging animals in vivo at three time points during a long-term survival study.

[Expression and clinical significance of Xiap and Caspase-3 protien in primary epithelia ovarian cancer].

PubMed

Chen, Wei; Peng, Ping

2010-07-01

To study the expression and clinical significance of Xiap, Caspase-3 protein in primary epithelia ovarian cancer. The Xiap and Caspase-3 were detected by immunohistochemical in 40 cases of epithelial ovarian cancer 20 cases of borderline ovarian tumor, 15 cases of benign ovarian tumor, and 15 normal ovarian tissues. There were significantly different between the expression of Xiap in epithelial ovarian cancer, borderline ovarian tumor, benign ovarian tumor and normal ovarian tissues. The expression of Caspase-3 in epithelial ovarian cancer and borderline ovarian tumor was significantly lower than that in benign ovarian tumor and normal ovarian tissue (P<0.01). The expression of Xiap in epithelial ovarian cancer was related to clinc stage, pathological grade and living. The expression of caspase-3 in epithelial ovarian cancer was related to clinc stage and living (P<0.01). The expressions of Xiap and Caspase-3 may be important roles for the formation and development of epithelia ovarian cancer. The expressions of Xiap and Caspase-3 are the poor prognostic factors in epithelial ovarian carcinomas.

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. © 2014 Blackwell Verlag GmbH.

Oocyte-somatic cell interactions in the human ovary-novel role of bone morphogenetic proteins and growth differentiation factors.

PubMed

Chang, Hsun-Ming; Qiao, Jie; Leung, Peter C K

2016-12-01

Initially identified for their capability to induce heterotopic bone formation, bone morphogenetic proteins (BMPs) are multifunctional growth factors that belong to the transforming growth factor β superfamily. Using cellular and molecular genetic approaches, recent studies have implicated intra-ovarian BMPs as potent regulators of ovarian follicular function. The bi-directional communication of oocytes and the surrounding somatic cells is mandatory for normal follicle development and oocyte maturation. This review summarizes the current knowledge on the physiological role and molecular determinants of these ovarian regulatory factors within the human germline-somatic regulatory loop. The regulation of ovarian function remains poorly characterized in humans because, while the fundamental process of follicular development and oocyte maturation is highly similar across species, most information on the regulation of ovarian function is obtained from studies using rodent models. Thus, this review focuses on the studies that used human biological materials to gain knowledge about human ovarian biology and disorders and to develop strategies for preventing, diagnosing and treating these abnormalities. Relevant English-language publications describing the roles of BMPs or growth differentiation factors (GDFs) in human ovarian biology and phenotypes were comprehensively searched using PubMed and the Google Scholar database. The publications included those published since the initial identification of BMPs in the mammalian ovary in 1999 through July 2016. Studies using human biological materials have revealed the expression of BMPs, GDFs and their putative receptors as well as their molecular signaling in the fundamental cells (oocyte, cumulus/granulosa cells (GCs) and theca/stroma cells) of the ovarian follicles throughout follicle development. With the availability of recombinant human BMPs/GDFs and the development of immortalized human cell lines, functional studies have demonstrated the physiological role of intra-ovarian BMPs/GDFs in all aspects of ovarian functions, from follicle development to steroidogenesis, cell-cell communication, oocyte maturation, ovulation and luteal function. Furthermore, there is crosstalk between these potent ovarian regulators and the endocrine signaling system. Dysregulation or naturally occurring mutations within the BMP system may lead to several female reproductive diseases. The latest development of recombinant BMPs, synthetic BMP inhibitors, gene therapy and tools for BMP-ligand sequestration has made the BMP pathway a potential therapeutic target in certain human fertility disorders; however, further clinical trials are needed. Recent studies have indicated that GDF8 is an intra-ovarian factor that may play a novel role in regulating ovarian functions in the human ovary. Intra-ovarian BMPs/GDFs are critical regulators of folliculogenesis and human ovarian functions. Any dysregulation or variations in these ligands or their receptors may affect the related intracellular signaling and influence ovarian functions, which accounts for several reproductive pathologies and infertility. Understanding the normal and pathological roles of intra-ovarian BMPs/GDFs, especially as related to GC functions and follicular fluid levels, will inform innovative approaches to fertility regulation and improve the diagnosis and treatment of ovarian disorders. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.

Histopathological survey of potential biomarkers for the assessment of contaminant related biological effects in species of fish and shellfish collected from Kuwait Bay, Arabian Gulf.

PubMed

Stentiford, G D; Massoud, M S; Al-Mudhhi, S; Al-Sarawi, M A; Al-Enezi, M; Lyons, B P

2014-07-01

The marine environment in Kuwait is dominated by Kuwait Bay, a shallow, depositional habitat vital for the breeding and propagation of marine organisms. The bay receives effluent inputs from industrial centres, ports, sewage outflows along with discharges from power and desalination plants. The major classes of pollutant discharged into the bay include petroleum hydrocarbons, metals, nutrients, cooling water and hyper-saline water. Further, the bay has been historically impacted by a deliberate release of oil and contamination with ordnance and shipwrecks during the 1991 Gulf war. With an aim to establish an integrated pollution effects monitoring programme in Kuwait, this paper describes the application of a quality assured approach to conduct a histopathology baseline survey in oriental sole (Synaptura orientalis) and the large-toothed flounder (Pseudorhombus arsius), which are two potential sentinel flatfish species present in the Arabian Gulf. Liver and gonadal histopathology revealed a range of pathologies similar to those previously observed in European and American pollution effects surveys that utilise flatfish (including pathology markers indicative of possible carcinogenesis and endocrine disruption). Further, we extended these studies to invertebrates (Jinga prawn, Metapenaeus affinis and the grooved tiger prawn, Penaeus semisulcatus) found within the Arabian Gulf. Such baseline data is essential before attempts are made to develop integrated monitoring programmes that aim to assess the health of fish and shellfish in relation to chemical contamination. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

Development of molecular markers for zebrafish (Danio rerio) ovarian follicle growth assessment following in-vitro culture in cryopreservation studies.

PubMed

Anil, Siji; Rawson, David; Zhang, Tiantian

2018-05-29

Development of in vitro culture protocol for early stage ovarian follicles of zebrafish is important since cryopreserved early stage ovarian follicles would need to be matured in vitro following cryopreservation before they can be fertilised. Development of molecular markers for zebrafish (Danio rerio) ovarian follicle growth assessment following in vitro culture of early stage zebrafish ovarian follicles in ovarian tissue fragments is reported here for the first time although some work has been reported for in vitro culture of isolated early stage zebrafish ovarian follicles. The main aim of the present study was to develop molecular markers in an optimised in vitro culture protocol for stage I and stage II zebrafish ovarian follicles in ovarian tissue fragments. The effect of concentration of the hormones human chorionic gonadotropin and follicle stimulating hormones, and additives such as Foetal Bovine Serum and Bovine Serum Albumin were studied. The results showed that early stage zebrafish ovarian fragments containing stage I and stage II follicles which are cultured in vitro for 24 h in 20% FBS and 100mIU/ml FSH in 90% L-15 medium at 28 °C can grow to the size of stage II and stage III ovarian follicles respectively. More importantly the follicle growth from stage I to stage II and from stage II to stage III were confirmed using molecular markers such as cyp19a1a (also known as P450aromA) and vtg1 genes respectively. However, no follicle growth was observed following cryopreservation and in vitro culture. Copyright © 2018 Elsevier Inc. All rights reserved.

76 FR 77415 - Fisheries Off West Coast States; Pacific Coast Groundfish Fishery; 2012 Specifications and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-13

... Specifications and Management Measures and Secretarial Amendment 1 AGENCY: National Marine Fisheries Service... Amendment 1 to the PCGFMP. Secretarial Amendment 1 contains the rebuilding plans for overfished species and new reference points for assessed flatfish species. DATES: This rule is effective January 1, 2012...

Comparison of Expression Profiles in Ovarian Epithelium In Vivo and Ovarian Cancer Identifies Novel Candidate Genes Involved in Disease Pathogenesis

PubMed Central

Emmanuel, Catherine; Gava, Natalie; Kennedy, Catherine; Balleine, Rosemary L.; Sharma, Raghwa; Wain, Gerard; Brand, Alison; Hogg, Russell; Etemadmoghadam, Dariush; George, Joshy; Birrer, Michael J.; Clarke, Christine L.; Chenevix-Trench, Georgia; Bowtell, David D. L.; Harnett, Paul R.; deFazio, Anna

2011-01-01

Molecular events leading to epithelial ovarian cancer are poorly understood but ovulatory hormones and a high number of life-time ovulations with concomitant proliferation, apoptosis, and inflammation, increases risk. We identified genes that are regulated during the estrous cycle in murine ovarian surface epithelium and analysed these profiles to identify genes dysregulated in human ovarian cancer, using publically available datasets. We identified 338 genes that are regulated in murine ovarian surface epithelium during the estrous cycle and dysregulated in ovarian cancer. Six of seven candidates selected for immunohistochemical validation were expressed in serous ovarian cancer, inclusion cysts, ovarian surface epithelium and in fallopian tube epithelium. Most were overexpressed in ovarian cancer compared with ovarian surface epithelium and/or inclusion cysts (EpCAM, EZH2, BIRC5) although BIRC5 and EZH2 were expressed as highly in fallopian tube epithelium as in ovarian cancer. We prioritised the 338 genes for those likely to be important for ovarian cancer development by in silico analyses of copy number aberration and mutation using publically available datasets and identified genes with established roles in ovarian cancer as well as novel genes for which we have evidence for involvement in ovarian cancer. Chromosome segregation emerged as an important process in which genes from our list of 338 were over-represented including two (BUB1, NCAPD2) for which there is evidence of amplification and mutation. NUAK2, upregulated in ovarian surface epithelium in proestrus and predicted to have a driver mutation in ovarian cancer, was examined in a larger cohort of serous ovarian cancer where patients with lower NUAK2 expression had shorter overall survival. In conclusion, defining genes that are activated in normal epithelium in the course of ovulation that are also dysregulated in cancer has identified a number of pathways and novel candidate genes that may contribute to the development of ovarian cancer. PMID:21423607

Fertility rescue and ovarian follicle growth promotion by bone marrow stem cell infusion.

PubMed

Herraiz, Sonia; Buigues, Anna; Díaz-García, César; Romeu, Mónica; Martínez, Susana; Gómez-Seguí, Inés; Simón, Carlos; Hsueh, Aaron J; Pellicer, Antonio

2018-05-01

To assess if infusion of human bone marrow-derived stem cells (BMDSCs) could promote follicle development in patients with impaired ovarian functions. Experimental design. University research laboratories. Immunodeficient NOD/SCID female mice. Human BMDSCs were injected into mice with chemotherapy-induced ovarian damage and into immunodeficient mice xenografted with human cortex from poor-responder patients (PRs). Follicle development, ovulation, and offspring. Apoptosis, proliferation, and vascularization were evaluated in mouse and human ovarian stroma. Fertility rescue and spontaneous pregnancies were achieved in mice ovaries mimicking PRs and ovarian insufficiency, induced by chemotherapy, after BMDSC infusion. Furthermore, BMDSC treatment resulted in production of higher numbers of preovulatory follicles, metaphase II oocytes, 2-cell embryos, and healthy pups. Stem cells promoted ovarian vascularization and cell proliferation, along with reduced apoptosis. In xenografted human ovarian tissues from PRs, infusion of BMDSCs and their CD133+ fraction led to their engraftment close to follicles, resulting in promotion of follicular growth, increases in E 2 secretion, and enhanced local vascularization. Our results raised the possibility that promoting ovarian angiogenesis by BMDSC infusion could be an alternative approach to improve follicular development in women with impaired ovarian function. NCT02240342. Copyright © 2018 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Fertility preservation for girls and young women with cancer: population-based validation of criteria for ovarian tissue cryopreservation.

PubMed

Wallace, W Hamish B; Smith, Alice Grove; Kelsey, Thomas W; Edgar, Angela E; Anderson, Richard A

2014-09-01

Ovarian tissue cryopreservation with later reimplantation has been shown to preserve fertility in adult women, but this approach remains unproven and experimental in children and adolescents. We aimed to assess the use of the Edinburgh selection criteria for ovarian tissue cryopreservation in girls and young women with cancer to determine whether we are offering this invasive procedure to the patients who are most at risk of premature ovarian insufficiency. Cryopreservation of ovarian tissue has been selectively offered to girls and young women with cancer who met the Edinburgh selection criteria since 1996. Between Jan 1, 1996, and June 30, 2012, 410 female patients younger than 18 years at diagnosis were treated for cancer (including leukaemia and brain tumours) at the Edinburgh Children's Cancer Centre, which serves the whole South East of Scotland region. We determined the ovarian status of these patients from review of clinical records and classified them as having premature ovarian insufficiency or not, or as unable to be determined. Patients younger than 12 years at time of data cutoff (Jan 31, 2013) were excluded from the analysis. 34 (8%) of the 410 patients met the Edinburgh selection criteria and were offered ovarian tissue cryopreservation before starting cancer treatment. 13 patients declined the procedure and 21 consented, and the procedure was completed successfully in 20 patients. Of the 20 patients who had ovarian tissue successfully cryopreserved, 14 were available for assessment of ovarian function. Of the 13 patients who had declined the procedure, six were available for assessment of ovarian function. Median age at the time of follow-up for the 20 assessable patients was 16·9 years (IQR 15·5-21·8). Of the 14 assessable patients who had successfully undergone ovarian cryopreservation, six had developed premature ovarian insufficiency at a median age of 13·4 years (IQR 12·5-14·6), one of whom also had a natural pregnancy. Of the six assessable patients who had declined the procedure, one had developed premature ovarian insufficiency. Assessment of ovarian function was possible for 141 of the 376 patients who were not offered cryopreservation; one of these patients had developed premature ovarian insufficiency. The cumulative probability of developing premature ovarian insufficiency after treatment was completed was significantly higher for patients who met the criteria for ovarian tissue cryopreservation than for those who did not (15-year probability 35% [95% CI 10-53] vs 1% [0-2]; p<0·0001; hazard ratio 56·8 [95% CI 6·2-521·6] at 10 years). The results of this analysis show that the Edinburgh selection criteria accurately identify the few girls and young women who will develop premature ovarian insufficiency, and validate their use for selection of patients for ovarian tissue cryopreservation. Further follow-up of this cohort of patients is likely to allow refinement of the criteria for this experimental procedure in girls and young women with cancer. UK Medical Research Council. Copyright © 2014 Wallace et al. Open Access article distributed under the terms of CC BY-NC-ND. Published by Elsevier Ltd. All rights reserved.

Ovulation and extra-ovarian origin of ovarian cancer

PubMed Central

Yang-Hartwich, Yang; Gurrea-Soteras, Marta; Sumi, Natalia; Joo, Won Duk; Holmberg, Jennie C.; Craveiro, Vinicius; Alvero, Ayesha B.; Mor, Gil

2014-01-01

The mortality rate of ovarian cancer remains high due to late diagnosis and recurrence. A fundamental step toward improving detection and treatment of this lethal disease is to understand its origin. A growing number of studies have revealed that ovarian cancer can develop from multiple extra-ovarian origins, including fallopian tube, gastrointestinal tract, cervix and endometriosis. However, the mechanism leading to their ovarian localization is not understood. We utilized in vitro, ex vivo, and in vivo models to recapitulate the process of extra-ovarian malignant cells migrating to the ovaries and forming tumors. We provided experimental evidence to support that ovulation, by disrupting the ovarian surface epithelium and releasing chemokines/cytokines, promotes the migration and adhesion of malignant cells to the ovary. We identified the granulosa cell-secreted SDF-1 as a main chemoattractant that recruits malignant cells towards the ovary. Our findings revealed a potential molecular mechanism of how the extra-ovarian cells can be attracted by the ovary, migrate to and form tumors in the ovary. Our data also supports the association between increased ovulation and the risk of ovarian cancer. Understanding this association will lead us to the development of more specific markers for early detection and better prevention strategies. PMID:25135607

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

PubMed

Schindler, Adolf E

2011-12-01

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

Simultaneous multiplane imaging of human ovarian cancer by volume holographic imaging

PubMed Central

Orsinger, Gabriel V.; Watson, Jennifer M.; Gordon, Michael; Nymeyer, Ariel C.; de Leon, Erich E.; Brownlee, Johnathan W.; Hatch, Kenneth D.; Chambers, Setsuko K.; Barton, Jennifer K.; Kostuk, Raymond K.; Romanowski, Marek

2014-01-01

Abstract. Ovarian cancer is the most deadly gynecologic cancer, a fact which is attributable to poor early detection and survival once the disease has reached advanced stages. Intraoperative laparoscopic volume holographic imaging has the potential to provide simultaneous visualization of surface and subsurface structures in ovarian tissues for improved assessment of developing ovarian cancer. In this ex vivo ovarian tissue study, we assembled a benchtop volume holographic imaging system (VHIS) to characterize the microarchitecture of 78 normal and 40 abnormal tissue specimens derived from ovarian, fallopian tube, uterine, and peritoneal tissues, collected from 26 patients aged 22 to 73 undergoing bilateral salpingo-oophorectomy, hysterectomy with bilateral salpingo-oophorectomy, or abdominal cytoreductive surgery. All tissues were successfully imaged with the VHIS in both reflectance- and fluorescence-modes revealing morphological features which can be used to distinguish between normal, benign abnormalities, and cancerous tissues. We present the development and successful application of VHIS for imaging human ovarian tissue. Comparison of VHIS images with corresponding histopathology allowed for qualitatively distinguishing microstructural features unique to the studied tissue type and disease state. These results motivate the development of a laparoscopic VHIS for evaluating the surface and subsurface morphological alterations in ovarian cancer pathogenesis. PMID:24676382

Multi-modality optical imaging of ovarian cancer in a post-menopausal mouse model

NASA Astrophysics Data System (ADS)

Watson, Jennifer M.; Rice, Photini Faith; Marion, Samuel L.; Bentley, David L.; Brewer, Molly A.; Utzinger, Urs; Hoyer, Patricia B.; Barton, Jennifer K.

2011-03-01

Our goal is to use optical imaging to detect cancer development on the sub cellular scale. By determining the microscopic changes that precede ovarian cancer we hope to develop a minimally invasive screening test for high risk patients. A mouse ovarian cancer model has been developed by treating mice with 4-Vinylcyclohexene Diepoxide to induce ovarian failure and 7, 12-Dimethylbenz[a]anthracene (DMBA) to induce ovarian cancer. Using optical coherence tomography (OCT) and multiphoton microscopy (MPM) we have obtained co-registered en face images of sixty-seven mouse ovaries ex vivo and forty-two ovaries in vivo. Preliminary analysis indicates that OCT and MPM can visualize ovarian microstructure. During the next year we will be completing a long term survival study using post-menopausal mice that have been treated with DMBA to induce cancer and imaged in vivo at time points before and after treatment.

Incidence of ovarian cancer after hysterectomy: a nationwide controlled follow up.

PubMed

Loft, A; Lidegaard, O; Tabor, A

1997-11-01

To estimate the risk of developing ovarian cancer after abdominal (total or subtotal) hysterectomy on benign indication. Prospective historical cohort study with 12.5 years of follow up. Denmark, nationwide. All Danish women (aged 0 to 99 years) having undergone hysterectomy with conservation of at least one ovary for a benign indication from 1977 to 1981 (n = 22,135). Follow up was conducted from 1977 to 1991. The reference group included all Danish women who had not undergone hysterectomy, age-standardised according to the hysterectomy group (n = 2,554,872). Registry data derived from the Danish National Register of Patients (diagnoses and operation codes) and the Civil Registration System (information about general population, including time of death). Incidence rate of ovarian cancer, lifetime risk of ovarian cancer, relative risk of ovarian cancer. Seventy-one women developed ovarian cancer on average 7.0 years after hysterectomy and 10,659 women in the reference group had ovarian cancer diagnosed after on average 6.4 years. The incidence rate of ovarian cancer was 0.27 per 1000 person-years in the group that had undergone hysterectomy and 0.34 per 1000 person-years in the general population (age-standardised). The extrapolated lifetime risk of developing ovarian cancer was 2.1% after hysterectomy and 2.7% in the general population (RR 0.78; 95% CI 0.60-0.96). The risk of ovarian cancer is lower among women who have undergone hysterectomy compared with those who have not. The protection seems to decrease with time.

Co-existence of breast and ovarian cancers in BRCA germ-line mutation carriers

PubMed Central

Dilawari, A; Cangiarella, J; Smith, J; Huang, A; Downey, A; Muggia, F

2008-01-01

The co-existence of breast and ovarian cancers in the same individual should raise suspicion of a hereditary process. Patients with either BRCA1 or BRCA2 germ-line mutations have an average risk of 39% and 11% respectively of developing ovarian cancer by the age of 70; they have a risk of 35–85% of developing breast cancer in their lifetime. We report here unusual pathologic features in a BRCA2 germ-line mutation carrier recently diagnosed with synchronous breast and ovarian cancers, and summarize the findings in six other women who were diagnosed with ovarian cancer either simultaneously with the diagnosis of breast cancer or at varying times after the diagnosis. While in most instances this may be a coincidental occurrence in highly susceptible individuals, the patient we highlight raises the provocative hypothesis that at times breast cancer metastasizes to the ovaries of mutation carriers and stimulates the development of an ovarian cancer as well as other cancers. In addition, these ovarian cancers may have different mechanisms of metastases predisposing them to travel to unusual sites. PMID:22275985

Local administration of platelet-derived growth factor B (PDGFB) improves follicular development and ovarian angiogenesis in a rat model of Polycystic Ovary Syndrome.

PubMed

Di Pietro, Mariana; Scotti, Leopoldina; Irusta, Griselda; Tesone, Marta; Parborell, Fernanda; Abramovich, Dalhia

2016-09-15

Alterations in ovarian angiogenesis are common features in Polycystic Ovary Syndrome (PCOS) patients; the most studied of these alterations is the increase in vascular endothelial growth factor (VEGF) production by ovarian cells. Platelet-derived growth factor B (PDGFB) and D (PDGFD) are decreased in follicular fluid of PCOS patients and in the ovaries of a rat model of PCOS. In the present study, we aimed to analyze the effects of local administration of PDGFB on ovarian angiogenesis, follicular development and ovulation in a DHEA-induced PCOS rat model. Ovarian PDGFB administration to PCOS rats partially restored follicular development, decreased the percentage of cysts, increased the percentage of corpora lutea, and decreased the production of anti-Müllerian hormone. In addition, PDGFB administration improved ovarian angiogenesis by reversing the increase in periendothelial cell area and restoring VEGF levels. Our results shed light into the mechanisms that lead to altered ovarian function in PCOS and provide new data for potential therapeutic strategies. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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

PubMed

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

2017-05-01

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

Development of a Mouse Model of Menopausal Ovarian Cancer

PubMed Central

Smith, Elizabeth R.; Wang, Ying; Xu, Xiang-Xi

2014-01-01

Despite significant understanding of the genetic mutations involved in ovarian epithelial cancer and advances in genomic approaches for expression and mutation profiling of tumor tissues, several key questions in ovarian cancer biology remain enigmatic: the mechanism for the well-established impact of reproductive factors on ovarian cancer risk remains obscure; cell of origin of ovarian cancer continue to be debated; and the precursor lesion, sequence, or events in progression remain to be defined. Suitable mouse models should complement the analysis of human tumor tissues and may provide clues to these questions currently perplexing ovarian cancer biology. A potentially useful model is the germ cell-deficient Wv (white spotting variant) mutant mouse line, which may be used to study the impact of menopausal physiology on the increased risk of ovarian cancer. The Wv mice harbor a point mutation in c-Kit that reduces the receptor tyrosine kinase activity to about 1–5% (it is not a null mutation). Homozygous Wv mutant females have a reduced ovarian germ cell reservoir at birth and the follicles are rapidly depleted upon reaching reproductive maturity, but other biological phenotypes are minimal and the mice have a normal life span. The loss of ovarian function precipitates changes in hormonal and metabolic activity that model features of menopause in humans. As a consequence of follicle depletion, the Wv ovaries develop ovarian tubular adenomas, a benign epithelial tumor corresponding to surface epithelial invaginations and papillomatosis that mark human ovarian aging. Ongoing work will test the possibility of converting the benign epithelial tubular adenomas into neoplastic tumors by addition of an oncogenic mutation, such as of Tp53, to model the genotype and biology of serous ovarian cancer. Model based on the Wv mice may have the potential to gain biological and etiological insights into ovarian cancer development and prevention. PMID:24616881

Molecular mechanisms associated with 46,XX disorders of sex development.

PubMed

Knarston, Ingrid; Ayers, Katie; Sinclair, Andrew

2016-03-01

In the female gonad, distinct signalling pathways activate ovarian differentiation while repressing the formation of testes. Human disorders of sex development (DSDs), such as 46,XX DSDs, can arise when this signalling is aberrant. Here we review the current understanding of the genetic mechanisms that control gonadal development, with particular emphasis on those that drive or inhibit ovarian differentiation. We discuss how disruption to these molecular pathways can lead to 46,XX disorders of ovarian development. Finally, we look at recently characterized novel genes and pathways that contribute and speculate how advances in technology will aid in further characterization of normal and disrupted human ovarian development. © 2016 Authors; published by Portland Press Limited.

US EPA WINTER FLOUNDER PROJECTS AND OTHER WORK IN RHODE ISLAND SALT PONDS

EPA Science Inventory

We will briefly summarize selected EPA research in Rhode Island's salt ponds from 2000 through 2003. In one project, during the summer of 2000, we used a 1.75 m2 drop sampler to quantify populations of juvenile flatfishes and other small nekton in Ninigret Pond. Mean abundance ...

Familial association of specific histologic types of ovarian malignancy with other malignancies.

PubMed

Lorenzo Bermejo, Justo; Rawal, Rajesh; Hemminki, Kari

2004-04-01

Population-based data on the familial association of specific histologic types of ovarian malignancy with other malignancies are limited. Such data may help to elucidate etiologic differences among histologic types of ovarian malignancy. The nationwide Swedish Family-Cancer Database, which includes 10.3 million individuals and 20,974 ovarian carcinomas, was used to calculate standardized incidence ratios and 95% confidence intervals for age- and histology-specific ovarian malignancies in women whose parents or siblings were affected with malignancies at the most common disease sites. Ovarian malignancy was found to be associated with ovarian, laryngeal, breast, endometrial, liver, and colon carcinoma, as well as myeloma; epithelial ovarian malignancy was found to be associated with ovarian, endometrial, and skin malignancies and with melanoma and myeloma; papillary serous cystadenocarcinoma was found to be associated with ovarian and skin malignancies and with myeloma; and endometrioid carcinoma was found to be associated with endometrial, ovarian, and prostate malignancies and with melanoma. For younger women (ages 40-45 years) whose mothers were affected with endometrial malignancies, the risk of developing endometrioid carcinoma was slightly greater than the risk of developing papillary serous cystadenocarcinoma. Specific types of ovarian malignancy may be associated with specific familial disease sites, with such associations depending on age at diagnosis; the strength of the observed associations varied according to histology. Associations were found between endometrioid carcinoma and endometrial malignancy and between serous carcinoma and Hodgkin disease. Copyright 2004 American Cancer Society.

Towards prevention of ovarian cancer.

PubMed

Ali, Aus Tariq

2018-01-01

Ovarian cancer is the leading cause of death of all gynaecological cancers. To date, there is no reliable, specific screening procedure for detecting ovarian cancer. The risk factors of ovarian cancer include modifiable and non-modifiable factors. The main goal of the ovarian cancer prevention program is to significantly reduce the risk of development of ovarian cancer and other cancers such as breast and/or peritoneal cancer. The application of non-surgical preventive approaches such as oral contraceptives, parity and breastfeeding has been shown to be highly protective against ovarian cancer development. Targeting inflammation has been also reported to be associated with a protective trend against ovarian cancer and can be achieved through either non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin or lifestyle modifications or both. Lifestyle modification that includes regular exercise, healthy diet supplemented with anti-oxidants and anti-inflammatory elements reduces the risk of the disease even further. Surgical protective approaches include; tubal ligation, hysterectomy and prophylactic bilateral salpingo-oophorectomy and the former is the most effective approach to protect against ovarian cancer. A better understanding of the risk factors of ovarian cancer and the current approaches to prevent it may increase the awareness and help to decrease the incidence of ovarian cancer, increase the five-year survival rate and decrease the mortality rate significantly in the general population especially among those at high risk for ovarian cancer. This review is an attempt to outline a potential program of ovarian cancer prevention and the potential challenges. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Diagnostic tool for early detection of ovarian cancers using Raman spectroscopy

NASA Astrophysics Data System (ADS)

Lieber, Chad A.; Molpus, Kelly; Brader, Kevin; Mahadevan-Jansen, Anita

2000-05-01

With an overall survival rate of about 35 percent, ovarian cancer claims more than 13,000 women in the US each year. It is estimated that roughly 1 in 70 women will develop ovarian cancer. Current screening techniques are challenged due to cost-effectiveness, variable false-positive results, and the asymptomatic nature of the early stages of ovarian cancer. The predominant screening method for ovarian cancers is transvaginal sonography (TVS). TVS is fairly accomplished at ovarian cancer detection, however it is inefficient in distinguishing between benign and malignant masses. Accurate diagnosis of the ovarian tumor relies on exploratory laparotomy, thus increasing the cost and hazard of false- positive screening methods. Raman spectroscopy has been sued successfully as a diagnostic tool in several organ systems in vitro. These studies have shown that Raman spectroscopy can be used to provide diagnosis of subtle changes in tissue pathology with high accuracy. Based on this success, we have developed a Raman spectroscopic system for application in the ovary. Using this system, the Raman signatures of normal and various types of non-normal human ovarian tissues were characterized in vitro. Raman spectra are being analyzed, and empirical as well as multivariate discriminatory algorithms developed. Based on the result of this study, a strategy for in vivo trials will be planned.

Distribution and abundance of juvenile demersal fishes in relation to summer hypoxia and other environmental variables in coastal Oregon, USA

NASA Astrophysics Data System (ADS)

Sobocinski, Kathryn L.; Ciannelli, Lorenzo; Wakefield, W. Waldo; Yergey, Matthew E.; Johnson-Colegrove, Angela

2018-05-01

The juvenile demersal fish assemblage along the Pacific Northwest coast has received little attention relative to adult life history stages since pioneering work in the 1970s. Increasing severity of hypoxia along the Oregon coast in recent years has prompted investigations into the response of biota in this region. We used summer data (2008-2013) from a beam trawl survey targeting juvenile demersal fishes in soft-bottom habitats along the Oregon coast to describe patterns of distribution and abundance at fixed sampling stations (from 30 m to 100 m depth). We relate the assemblage and abundance of the common species to environmental variables and analyze condition of recently settled fish (<50 mm SL). Most of the captured fishes were young-of-the-year flatfishes, dominated by Butter Sole (Isopsetta isolepis), English Sole (Parophrys vetulus), Speckled Sanddab (Citharichthys stigmaeus), and Pacific Sanddab (Citharichthys sordidus). Community analysis of the full dataset showed some variation in species richness among years and high evenness across all sampling sites and years. Depth was a structuring variable for the community, indicated by multivariate nonmetric multidimensional scaling analysis. Generalized additive models for common flatfish species abundances during the summer months indicated depth preferences, with Butter Sole, English Sole, and Speckled Sanddab at shallower locations and Pacific Sanddab occurring at deeper locations farther offshore. Additionally, while most common species were collected in high abundances in hypoxic conditions, dissolved oxygen was a significant factor in determining flatfish abundance. Condition factor was weakly negatively impacted by low dissolved oxygen for the species assessed, but the strength of the relationship varied by species. Increased sampling frequency and spatial coverage would improve our understanding of this community, especially in light of changing environmental drivers such as decreasing pH, warming water, and episodic periods of low dissolved oxygen coinciding with settlement for many species.

Follicle dynamics: visualization and analysis of follicle growth and maturation using murine ovarian tissue culture.

PubMed

Murase, Tomohiko; Iwase, Akira; Komatsu, Kouji; Bayasula; Nakamura, Tomoko; Osuka, Satoko; Takikawa, Sachiko; Goto, Maki; Kotani, Tomomi; Kikkawa, Fumitaka

2018-02-01

To visualize and analyze follicle development in ovarian tissue culture using physiological concentrations of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in order to establish an ovarian tissue culture system that enables efficient in vitro growth of follicles. Ovarian tissues from 4-week-old female ICR mice were sliced and cultured. Images of ovarian tissues in culture were obtained at 24-h or 30-min intervals by using a microscope. The area of each follicle observed in the ovarian tissue slices was tracked and analyzed in association with oocyte maturation. We were able to track the development of each follicle using this culture system. Follicle growth was associated with oocyte maturation. Meiotically matured oocytes (MII) were obtained from 33% of all follicles investigated. Approximately, a quarter of follicles (24%) did not grow and resulted in atresia. Follicle dynamics were successfully visualized and analyzed in murine ovarian tissue culture. We were able to obtain mature oocytes from the fully grown follicles in vitro. This culture system would be helpful for efficient in vitro culturing of ovarian tissues.

Tetraploid cells from cytokinesis failure induce aneuploidy and spontaneous transformation of mouse ovarian surface epithelial cells.

PubMed

Lv, Lei; Zhang, Tianwei; Yi, Qiyi; Huang, Yun; Wang, Zheng; Hou, Heli; Zhang, Huan; Zheng, Wei; Hao, Qiaomei; Guo, Zongyou; Cooke, Howard J; Shi, Qinghua

2012-08-01

Most ovarian cancers originate from the ovarian surface epithelium and are characterized by aneuploid karyotypes. Aneuploidy, a consequence of chromosome instability, is an early event during the development of ovarian cancers. However, how aneuploid cells are evolved from normal diploid cells in ovarian cancers remains unknown. In the present study, cytogenetic analyses of a mouse syngeneic ovarian cancer model revealed that diploid mouse ovarian surface epithelial cells (MOSECs) experienced an intermediate tetraploid cell stage, before evolving to aneuploid (mainly near-tetraploid) cells. Using long-term live-cell imaging followed by fluorescence in situ hybridization (FISH), we demonstrated that tetraploid cells originally arose from cytokinesis failure of bipolar mitosis in diploid cells, and gave rise to aneuploid cells through chromosome mis-segregation during both bipolar and multipolar mitoses. Injection of the late passage aneuploid MOSECs resulted in tumor formation in C57BL/6 mice. Therefore, we reveal a pathway for the evolution of diploid to aneuploid MOSECs and elucidate a mechanism for the development of near-tetraploid ovarian cancer cells.

Advancing ovarian folliculometry with selective plane illumination microscopy

NASA Astrophysics Data System (ADS)

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

2016-12-01

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

Sustainable use of flatfish resources: Addressing the credibility crisis in mixed fisheries management

NASA Astrophysics Data System (ADS)

Rijnsdorp, A. D.; Daan, N.; Dekker, W.; Poos, J. J.; Van Densen, W. L. T.

2007-02-01

Many flatfish species are caught in mixed demersal trawl fisheries and managed by Total Allowable Catch (TAC). Despite decades of fisheries management, several major stocks are severely depleted. Using the Common Fisheries Policy (CFP) as an example, the failure of mixed-fisheries management is analysed by focussing on: the management system; the role of science; the role of managers and politicians; the response of fisheries to management. Failure of the CFP management could be ascribed to: incorrect management advice owing to bias in stock assessments; the tendency of politicians to set the TAC well above the recommended level; and non-compliance of the fisheries with the management regulations. We conclude that TAC management, although apparently successful in some single-species fisheries, inevitably leads to unsustainable exploitation of stocks caught in mixed demersal fisheries as it promotes discarding of over-quota catch and misreporting of catches, thereby corrupting the basis of the scientific advice and increasing the risk of stock collapse. This failure in mixed demersal fisheries has resulted in the loss of credibility of both scientists and managers, and has undermined the support of fishermen for management regulations. An approach is developed to convert the TAC system into a system that controls the total allowable effort (TAE). The approach takes account of the differences in catch efficiency between fleets as well as seasonal changes in the distribution of the target species and can also be applied in the recovery plans for rebuilding specific components of the demersal fish community, such as plaice, cod and hake.

Relationship between Numerous Mast Cells and Early Follicular Development in Neonatal MRL/MpJ Mouse Ovaries

PubMed Central

Nakamura, Teppei; Otsuka, Saori; Ichii, Osamu; Sakata, Yuko; Nagasaki, Ken-Ichi; Hashimoto, Yoshiharu; Kon, Yasuhiro

2013-01-01

In the neonatal mouse ovary, clusters of oocytes called nests break into smaller cysts and subsequently form individual follicles. During this period, we found numerous mast cells in the ovary of MRL/MpJ mice and investigated their appearance and morphology with follicular development. The ovarian mast cells, which were already present at postnatal day 0, tended to localize adjacent to the surface epithelium. Among 11 different mouse strains, MRL/MpJ mice possessed the greatest number of ovarian mast cells. Ovarian mast cells were also found in DBA/1, BALB/c, NZW, and DBA/2 mice but rarely in C57BL/6, NZB, AKR, C3H/He, CBA, and ICR mice. The ovarian mast cells expressed connective tissue mast cell markers, although mast cells around the surface epithelium also expressed a mucosal mast cell marker in MRL/MpJ mice. Some ovarian mast cells migrated into the oocyte nests and directly contacted the compressed and degenerated oocytes. In MRL/MpJ mice, the number of oocytes in the nest was significantly lower than in the other strains, and the number of oocytes showed a positive correlation with the number of ovarian mast cells. The gene expression of a mast cell marker also correlated with the expression of an oocyte nest marker, suggesting a link between the appearance of ovarian ? 4mast cells and early follicular development. Furthermore, the expression of follicle developmental markers was significantly higher in MRL/MpJ mice than in C57BL/6 mice. These results indicate that the appearance of ovarian mast cells is a unique phenotype of neonatal MRL/MpJ mice, and that ovarian mast cells participate in early follicular development, especially nest breakdown. PMID:24124609

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

DTIC Science & Technology

2007-11-01

information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services , Directorate for Information...ovarian cancer in Women and Hens”. First AACR International Conference on Molecular Diagnostics in Cancer Therapeutic Development, Sep 12-15, 2006...associated with ovarian cancer in humans and hens“ Presented at the 1st International Aegean conference on Ovarian Cancer, June 2006,Crete, Greece 4

75 FR 31321 - Fisheries of the Exclusive Economic Zone Off Alaska; Rock Sole, Flathead Sole, and “Other...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-03

.... 0910131363-0087-02] RIN 0648-XW74 Fisheries of the Exclusive Economic Zone Off Alaska; Rock Sole, Flathead... participating in the Amendment 80 limited access fishery in the Bering Sea and Aleutian Islands management area... the trawl rock sole, flathead sole, and ``other flatfish'' fishery category by vessels participating...

USE OF A RHODE ISLAND SALT POND BY JUVENILE WINTER FLOUNDER, PSEUDOPLEURONECTES AMERICANUS

EPA Science Inventory

We used a 1.75 m2 drop ring sampler in June and July of 2000 to quantify populations of juvenile flatfishes and other small nekton in Ninigret Pond, Rhode Island. The drop sampler was deployed in approximately 1 m of water from a boom mounted on the bow of a small boat. Abundance...

75 FR 76372 - Fisheries of the Exclusive Economic Zone Off Alaska; Bering Sea and Aleutian Islands; Proposed...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-08

... intends to have the information available for the assessment cycle in the fall of 2011. At the October... sole, rock sole, Kamchatka flounder, sharks, squid, sculpins, and octopus to be included in the final... flounder, Greenland turbot, rock sole, Alaska plaice, other flatfish, and rougheye rockfish. The biomass...

Immunotherapy for Ovarian Cancer: What's Next?

PubMed Central

Kandalaft, Lana E.; Powell, Daniel J.; Singh, Nathan; Coukos, George

2011-01-01

In the past decade, we have witnessed important gains in the treatment of ovarian cancer; however, additional advances are required to reduce mortality. With compelling evidence that ovarian cancers are immunogenic tumors, immunotherapy should be further pursued and optimized. The dramatic advances in laboratory and clinical procedures in cellular immunotherapy, along with the development of powerful immunomodulatory antibodies, create new opportunities in ovarian cancer therapeutics. Herein, we review current progress and future prospects in vaccine and adoptive T-cell therapy development as well as immunomodulatory therapy tools available for immediate clinical testing. PMID:21079136

Ovarian cancer stem cells more questions than answers.

PubMed

Ottevanger, Petronella Beatrix

2017-06-01

Epithelial ovarian cancer is a highly lethal disease, which is usually diagnosed at a late stage with extensive metastases in the abdominal cavity. Ovarian cancer either develops from the ovarian surface epithelium (OSE) or from serous intra-epithelial carcinoma (STIC). Primary therapy consists of debulking surgery and platinum based chemotherapy. The success of debulking surgery depends on surgical skills but also on the gene signature of the tumour. Debulking surgery combined with first line platinum based chemotherapy, frequently leads to complete remission. However, most ovarian cancers relapse. Once the disease has relapsed, the interval between subsequent therapies decreases steadily due to rapid progression and therapy resistance. Research on therapy resistance of ovarian cancer is frequently devoted to genetic alterations in cancer cells, leading to drug inactivation, enhanced DNA repair mechanisms and intracellular pathway derangements. However the knowledge of ovarian cancer stem cells (OCSC) and the role they play in the development of cancer and therapy resistance is sparse. In this review current knowledge on the characteristics of OCSCs and the micro environmental mechanisms leading to the development or activation of OCSCs resulting in ovarian cancer is reviewed. Moreover the role of OCSC in both surgical and systemic therapy resistance and the relation with epithelial mesenchymal transformation (EMT) is discussed, as are micro-environmental signals leading to OCSC or EMT activation. Copyright © 2017 The Author. Published by Elsevier Ltd.. All rights reserved.

Follicle Depletion Provides a Permissive Environment for Ovarian Carcinogenesis

PubMed Central

Wang, Ying; Cai, Kathy Qi; Smith, Elizabeth R.; Yeasky, Toni M.; Moore, Robert; Ganjei-Azar, Parvin; Klein-Szanto, Andres J.; Godwin, Andrew K.; Hamilton, Thomas C.

2016-01-01

We modeled the etiology of postmenopausal biology on ovarian cancer risk using germ cell-deficient white-spotting variant (Wv) mice, incorporating oncogenic mutations. Ovarian cancer incidence is highest in peri- and postmenopausal women, and epidemiological studies have established the impact of reproductive factors on ovarian cancer risk. Menopause as a result of ovarian follicle depletion is thought to contribute to higher cancer risk. As a consequence of follicle depletion, female Wv mice develop ovarian tubular adenomas, a benign epithelial tumor corresponding to surface epithelial invaginations and papillomatosis frequently found in postmenopausal human ovaries. Lineage tracing using MISR2-Cre indicated that the tubular adenomas that developed in Wv mice were largely derived from the MISR2 lineage, which marked only a fraction of ovarian surface and oviduct epithelial cells in wild-type tissues. Deletion of p27, either heterozygous or homozygous, was able to convert the benign tubular adenomas into more proliferative tumors. Restricted deletion of p53 in Wv/Wv mice by either intrabursal injection of adenoviral Cre or inclusion of the MISR2-Cre transgene also resulted in augmented tumor growth. This finding suggests that follicle depletion provides a permissive ovarian environment for oncogenic transformation of epithelial cells, presenting a mechanism for the increased ovarian cancer risk in postmenopausal women. PMID:27354067

Individualized controlled ovarian stimulation in expected poor-responders: an update.

PubMed

Haahr, Thor; Esteves, Sandro C; Humaidan, Peter

2018-03-09

Controlled ovarian stimulation with subsequent multi-follicular development continues to be a keystone in ART. Evidence supports an individualized approach to ovarian stimulation, usually involving combinations of ovarian reserve tests, body mass index and age to tailor the exogenous gonadotropin dose, and potentially adjuvant treatment aiming for high safety and a shortening of time to live birth. While stimulation and trigger concepts have been developed successfully in normo- and hyperresponder patients, the poor responder patient remains difficult to manage. However, recent advances in definition and classification of the expected poor ovarian responder patient might enable a more accurate and clinically useful interpretation of new treatment concepts in a more homogenous study population. In the present review, we discuss the classification of the expected poor ovarian responder patient as well as clinically useful measurements of efficacy for controlled ovarian stimulation, and finally, we discuss the evidence for clinical management of patients with expected poor ovarian response, including adjuvant treatments such as growth hormone, androgens, and LH activity.In conclusion, the best available evidence supports that the treatment of the expected poor ovarian response patient should be individualized in all steps of ART, including the choice of GnRH analogue, the gonadotropin type and dose, ovulation trigger, and the possible use of adjuvant therapies.

Regulation of Ovarian Cancer Stem Cells or Tumor-Initiating Cells

PubMed Central

Kwon, Mi Jeong; Shin, Young Kee

2013-01-01

Cancer stem cells or tumor-initiating cells (CSC/TICs), which can undergo self-renewal and differentiation, are thought to play critical roles in tumorigenesis, therapy resistance, tumor recurrence and metastasis. Tumor recurrence and chemoresistance are major causes of poor survival rates of ovarian cancer patients, which may be due in part to the existence of CSC/TICs. Therefore, elucidating the molecular mechanisms responsible for the ovarian CSC/TICs is required to develop a cure for this malignancy. Recent studies have indicated that the properties of CSC/TICs can be regulated by microRNAs, genes and signaling pathways which also function in normal stem cells. Moreover, emerging evidence suggests that the tumor microenvironments surrounding CSC/TICs are crucial for the maintenance of these cells. Similarly, efforts are now being made to unravel the mechanism involved in the regulation of ovarian CSC/TICs, although much work is still needed. This review considers recent advances in identifying the genes and pathways involved in the regulation of ovarian CSC/TICs. Furthermore, current approaches targeting ovarian CSC/TICs are described. Targeting both CSC/TICs and bulk tumor cells is suggested as a more effective approach to eliminating ovarian tumors. Better understanding of the regulation of ovarian CSC/TICs might facilitate the development of improved therapeutic strategies for recurrent ovarian cancer. PMID:23528891

Social interactions and their connection to aggression and ovarian development in orphaned worker bumblebees (Bombus impatiens).

PubMed

Sibbald, E D; Plowright, C M S

2014-03-01

This study examines the social dynamics of reproductive conflict. Orphaned worker bumblebees (Bombus impatiens) with comparatively high or low levels of social activity were paired to determine whether aggression and reproduction could be traced to earlier social interactions. The workers were paired according to their levels of social activity (a socially active+another socially active worker, socially active+socially inactive, and two socially inactive workers). The presence or absence of brood was also manipulated. The absence of brood increased both aggression and ovarian development, suggesting that aggression and reproduction are associated or that there is a third variable that affects both. Socially active pairs were significantly more aggressive: here, social activity can be taken as an early indicator of aggression. No such effect, however, was obtained on ovarian development as the socially active pairs did not differ on their degree of ovarian development compared to the others. Within the socially active+socially inactive pairs, the socially active worker did not have more developed ovaries and was not more aggressive than her socially inactive partner. Results highlight that environmental conditions (the absence of brood) can predict ovarian development and although social activity can be observed prior to aggression, differences in aggression do not translate into differences in ovarian development under these conditions. Copyright © 2013 Elsevier B.V. All rights reserved.

Normal female phenotype and ovarian development despite the ovarian expression of the sex-determining region of Y chromosome (SRY) in a 46,XX/69,XXY diploid/triploid mosaic child conceived after in vitro fertilization-intracytoplasmic sperm injection.

PubMed

Oktem, Ozgur; Paduch, Darius A; Xu, Kangpu; Mielnik, Anna; Oktay, Kutluk

2007-03-01

Diploid/triploid mosaicism (mixoploidy) is a rare chromosomal abnormality characterized by mental and growth retardation, hypotonia, and dysmorphic features such as facial asymmetry, low-set ears, and syndactyly. All 46,XX/69,XXY cases fall into three phenotypic groups: male with testicular development, ovotestis disorder of sex development (DSD), or undervirilized male DSD. All phenotypic females with diploid/triploid mosaic reported so far had 46,XX/69,XXX karyotype. We report an 8-year-old girl conceived after in vitro fertilization-intracytoplasmic sperm injection with normal internal/external genital and ovarian development despite 46,XX/69,XXY mosaicism and normal expression of sex-determining region of Y chromosome (SRY) in her gonads. Because of the increased risk of gonadoblastoma resulting from Y chromosome mosaicism, her ovaries were removed by laparoscopy. Ovarian tissue was analyzed histologically as well as by fluorescence in situ hybridization, PCR, and RT-PCR amplification to determine the localization of Y chromosome and expression of SRY and DAX1 mRNA. Methylation-specific PCR was used to assess the inactivation pattern of X chromosomes. By laparoscopy, internal female genital anatomy appeared to be normal. Cytogenetic and molecular methods confirmed the presence of intact and functionally active Y chromosome in the ovary. Strikingly, histological assessment of the gonads showed normal ovarian architecture with abundant primordial follicles despite the presence of the Y chromosome in ovarian follicles and the expression of SRY mRNA in gonadal tissue. This case illustrates that normal ovarian development is possible in the presence of Y chromosome in ovarian follicles and despite the expression of SRY in ovarian tissue. Furthermore, this is the first documented case of mixoploidy after in vitro fertilization-intracytoplasmic sperm injection and the only phenotypic female with 46,XX/69,XXY karyotype.

Role of chemokine network in the development and progression of ovarian cancer: a potential novel pharmacological target.

PubMed

Barbieri, Federica; Bajetto, Adriana; Florio, Tullio

2010-01-01

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

Long non-coding RNA ZFAS1 interacts with miR-150-5p to regulate Sp1 expression and ovarian cancer cell malignancy.

PubMed

Xia, Bairong; Hou, Yan; Chen, Hong; Yang, Shanshan; Liu, Tianbo; Lin, Mei; Lou, Ge

2017-03-21

We reported that long non-coding RNA ZFAS1 was upregulated in epithelial ovarian cancer tissues, and was negatively correlated to the overall survival rate of patients with epithelial ovarian cancer in this study. While depletion of ZFAS1 inhibited proliferation, migration, and development of chemoresistance, overexpression of ZFAS1 exhibited an even higher proliferation rate, migration activity, and chemoresistance in epithelial ovarian cancer cell lines. We further found miR-150-5p was a potential target of ZFAS1, which was downregulated in epithelial ovarian cancer tissue. MiR-150-5p subsequently inhibited expression of transcription factor Sp1, as evidence by luciferase assays. Inhibition of miR-150-5p rescued the suppressed proliferation and migration induced by depletion of ZFAS1 in epithelial ovarian cancer cells, at least in part. Taken together, our findings revealed a critical role of ZFAS1/miR-150-5p/Sp1 axis in promoting proliferation rate, migration activity, and development of chemoresistance in epithelial ovarian cancer. And ZFAS1/miR-150-5p may serve as novel markers and therapeutic targets of epithelial ovarian cancer.

7,12-Dimethylbenz[a]anthracene-Induced Malignancies in a Mouse Model of Menopause

PubMed Central

Marion, Samuel L; Watson, Jennifer; Sen, Nivedita; Brewer, Molly A; Barton, Jennifer K; Hoyer, Patricia B

2013-01-01

Ovarian cancer has a high mortality rate because there are few symptoms in early disease development. The incidence of ovarian cancer increases in women after menopause. Understanding early events in this disease can best be achieved by using animal models. Therefore, the objective of this study was to develop and track the onset of ovarian tumorigenesis in mice mimicking characteristics of postmenopausal epithelial cancer in women. Female B6C3F1 mice (age, 28 d) received 4-vinylcyclohexene diepoxide (VCD, 160 mg/kg IV daily for 20 d) to cause ovarian failure. Four months after VCD treatment, via surgical intervention, each mouse received a single injection of 7,12-dimethylbenz[a]anthracene (DMBA) or vehicle control (sesame oil) under the bursa of the right ovary to cause ovarian neoplasms. The experimental groups were untreated controls (Con–Con), DMBA-treatment only (Con–DMBA), VCD treatment only (VCD–Con), and VCD+DMBA-treated (VCD+DMBA) mice. At 3, 5, 7, and 9 mo after DMBA injection, ovaries were collected for histologic and immunohistochemical evaluation. No tumors developed in Con–Con mice. All VCD-treated mice (with or without DMBA) exhibited ovarian failure. Mice that received both VCD and DMBA exhibited tumors at 3 mo (50%), 5 mo (14%), 7 mo (90%), and 9 mo (57%) after DMBA treatment; 31% of the tumors were epithelial in origin. Our findings confirm that inducing ovarian tumors in mice by chemical means is an effective method for studying early stages of tumor development that may be relevant to epithelial ovarian cancers that arise in postmenopausal women. PMID:23561932

7,12-dimethylbenz[a]anthracene-induced malignancies in a mouse model of menopause.

PubMed

Marion, Samuel L; Watson, Jennifer; Sen, Nivedita; Brewer, Molly A; Barton, Jennifer K; Hoyer, Patricia B

2013-02-01

Ovarian cancer has a high mortality rate because there are few symptoms in early disease development. The incidence of ovarian cancer increases in women after menopause. Understanding early events in this disease can best be achieved by using animal models. Therefore, the objective of this study was to develop and track the onset of ovarian tumorigenesis in mice mimicking characteristics of postmenopausal epithelial cancer in women. Female B6C3F1 mice (age, 28 d) received 4-vinylcyclohexene diepoxide (VCD, 160 mg/kg IV daily for 20 d) to cause ovarian failure. Four months after VCD treatment, via surgical intervention, each mouse received a single injection of 7,12-dimethylbenz[a]anthracene (DMBA) or vehicle control (sesame oil) under the bursa of the right ovary to cause ovarian neoplasms. The experimental groups were untreated controls (Con-Con), DMBA-treatment only (Con-DMBA), VCD treatment only (VCD-Con), and VCD+DMBA-treated (VCD+DMBA) mice. At 3, 5, 7, and 9 mo after DMBA injection, ovaries were collected for histologic and immunohistochemical evaluation. No tumors developed in Con-Con mice. All VCD-treated mice (with or without DMBA) exhibited ovarian failure. Mice that received both VCD and DMBA exhibited tumors at 3 mo (50%), 5 mo (14%), 7 mo (90%), and 9 mo (57%) after DMBA treatment; 31% of the tumors were epithelial in origin. Our findings confirm that inducing ovarian tumors in mice by chemical means is an effective method for studying early stages of tumor development that may be relevant to epithelial ovarian cancers that arise in postmenopausal women.

Ovarian and cervical cancer awareness: development of two validated measurement tools.

PubMed

Simon, Alice E; Wardle, Jane; Grimmett, Chloe; Power, Emily; Corker, Elizabeth; Menon, Usha; Matheson, Lauren; Waller, Jo

2012-07-01

The aim of the study was to develop and validate measures of awareness of symptoms and risk factors for ovarian and cervical cancer (Ovarian and Cervical Cancer Awareness Measures). Potentially relevant items were extracted from the literature and generated by experts. Four validation studies were carried out to establish reliability and validity. Women aged 21-67 years (n=146) and ovarian and cervical cancer experts (n=32) were included in the studies. Internal reliability was assessed psychometrically. Test-retest reliability was assessed over a 1-week interval. To establish construct validity, Cancer Awareness Measure (CAM) scores of cancer experts were compared with equally well-educated comparison groups. Sensitivity to change was tested by randomly assigning participants to read either a leaflet giving information about ovarian/cervical cancer or a leaflet with control information, and then completing the ovarian/cervical CAM. Internal reliability (Cronbach's α=0.88 for the ovarian CAM and α=0.84 for the cervical CAM) and test-retest reliability (r=0.84 and r=0.77 for the ovarian and cervical CAMs, respectively) were both high. Validity was demonstrated with cancer experts achieving higher scores than controls [ovarian CAM: t(36)= -5.6, p<0.001; cervical CAM: t(38)= -3.7, p=0.001], and volunteers who were randomised to read a cancer leaflet scored higher than those who received a control leaflet [ovarian CAM: t(49)=7.5, p<0.001; cervical CAM: t(48)= -5.5, p<0.001]. This study demonstrates the psychometric properties of the ovarian and cervical CAMs and supports their utility in assessing ovarian and cervical cancer awareness in the general population.

Ovarian and cervical cancer awareness: development of two validated measurement tools

PubMed Central

Simon, Alice E; Wardle, Jane; Grimmett, Chloe; Power, Emily; Corker, Elizabeth; Menon, Usha; Matheson, Lauren; Waller, Jo

2012-01-01

Background The aim of the study was to develop and validate measures of awareness of symptoms and risk factors for ovarian and cervical cancer (Ovarian and Cervical Cancer Awareness Measures). Methods Potentially relevant items were extracted from the literature and generated by experts. Four validation studies were carried out to establish reliability and validity. Women aged 21–67 years (n=146) and ovarian and cervical cancer experts (n=32) were included in the studies. Internal reliability was assessed psychometrically. Test-retest reliability was assessed over a 1-week interval. To establish construct validity, Cancer Awareness Measure (CAM) scores of cancer experts were compared with equally well-educated comparison groups. Sensitivity to change was tested by randomly assigning participants to read either a leaflet giving information about ovarian/cervical cancer or a leaflet with control information, and then completing the ovarian/cervical CAM. Results Internal reliability (Cronbach's α=0.88 for the ovarian CAM and α=0.84 for the cervical CAM) and test-retest reliability (r=0.84 and r=0.77 for the ovarian and cervical CAMs, respectively) were both high. Validity was demonstrated with cancer experts achieving higher scores than controls [ovarian CAM: t(36)= –5.6, p<0.001; cervical CAM: t(38)= –3.7, p=0.001], and volunteers who were randomised to read a cancer leaflet scored higher than those who received a control leaflet [ovarian CAM: t(49)=7.5, p<0.001; cervical CAM: t(48)= –5.5, p<0.001]. Conclusions This study demonstrates the psychometric properties of the ovarian and cervical CAMs and supports their utility in assessing ovarian and cervical cancer awareness in the general population. PMID:21933805

New models of hematogenous ovarian cancer metastasis demonstrate preferential spread to the ovary and a requirement for the ovary for abdominal dissemination.

PubMed

Coffman, Lan G; Burgos-Ojeda, Daniela; Wu, Rong; Cho, Kathleen; Bai, Shoumei; Buckanovich, Ronald J

2016-09-01

Emerging evidence suggest that many high-grade serous "ovarian" cancers (HGSOC) start in the fallopian tube. Cancer cells are then recruited to the ovary and then spread diffusely through the abdomen. The mechanism of ovarian cancer spread was thought to be largely due to direct shedding of tumor cells into the peritoneal cavity with vascular spread being of limited importance. Recent work challenges this dogma, suggesting hematogenous spread of ovarian cancer may play a larger role in ovarian cancer cell metastasis than previously thought. One reason the role of vascular spread of ovarian cancer has not been fully elucidated is the lack of easily accessible models of vascular ovarian cancer metastasis. Here, we present 3 metastatic models of ovarian cancer which confirm the ability of ovarian cancer to hematogenously spread. Strikingly, we observe a high rate of metastasis to the ovary with the development of ascites in these models. Interestingly, oophorectomy resulted in a complete loss of peritoneal metastases and ascites. Taken together, our data indicate that hematogenously disseminated HGSOC cells have a unique tropism for the ovary and that hematogenous spread in ovarian cancer may be more common than appreciated. Furthermore, our studies support a critical role for the ovary in promoting HGSOC cell metastasis to the abdomen. The models developed here represent important new tools to evaluate both the mechanism of cancer cell recruitment to the ovary and understand and target key steps in ovarian cancer metastasis. Copyright © 2016 Elsevier Inc. All rights reserved.

Ovarian aging: latest thoughts on assessment and management.

PubMed

Younis, Johnny S

2011-12-01

In the past few decades, women have been intentionally delaying pregnancy and ovarian aging has become one of the most detrimental factors of pregnancy achievement. This review will discuss contemporary methods of ovarian aging assessment and present an overview of current management strategies. Antimullerian hormone (AMH) and antral follicle count (AFC) seem to be the most reliable predictors of ovarian aging appraisal. Nevertheless, they have not been shown to predict pregnancy achievement in assisted reproduction. Heritability has a high impact on ovarian aging. Employing several genetic approaches, it is now being widely investigated, but the task is far from being accomplished. Although multivariate models have not been proven to be superior to AFC, new data support the notion that chronological age and genetic markers inclusion may increase their reliability. Several strategies have been suggested to treat ovarian aging in assisted reproductive technology (ART) settings. None of the stimulation protocol manipulations have been found to be advantageous and individualization of treatment is still recommended. Ovarian priming by different androgen preparations has been shown to be promising but more randomized controlled trials are needed to support these findings. Except for oocyte donation other ART strategies have not shown a convincing benefit for ovarian aging. The new development of oocyte vitrification may well introduce opportunities for fertility preservation to women at risk of ovarian aging. Proper assessment and detection of ovarian aging, employing current or developing predictors of ovarian reserve, especially genetic tests, may enable health providers to recommend, at appropriate biological time, early pregnancy achievement or fertility preservation in women at risk.

Pipeline inspection using an autonomous underwater vehicle

DOE Office of Scientific and Technical Information (OSTI.GOV)

Egeskov, P.; Bech, M.; Bowley, R.

1995-12-31

Pipeline inspection can be carried out by means of small Autonomous Underwater Vehicles (AUVs), operating either with a control link to a surface vessel, or totally independently. The AUV offers an attractive alternative to conventional inspection methods where Remotely Operated Vehicles (ROVs) or paravanes are used. A flatfish type AUV ``MARTIN`` (Marine Tool for Inspection) has been developed for this purpose. The paper describes the proposed types of inspection jobs to be carried out by ``MARTIN``. The design and construction of the vessel, its hydrodynamic properties, its propulsion and control systems are discussed. The pipeline tracking and survey systems, asmore » well as the launch and recovery systems are described.« less

Uptake and selective partitioning of dietary lipids to ovarian and muscle tissue of maturing female coho salmon, Oncorhynchus kisutch, during secondary oocyte growth.

PubMed

Johnson, Ronald B; Kroeger, Eric L; Reichert, William L; Carter, Cameron S; Rust, Michael B

2017-06-01

Female coho salmon, Oncorhynchus kisutch, were fed one of two experimental feeds containing lipids with markedly different stable 13 C isotope signatures during the late cortical alveolus, lipid droplet, and vitellogenesis stages of secondary oocyte growth. Ovarian and muscle lipids fatty acid concentrations were significantly affected by treatment during all three stages of development. Stable 13 C isotope analyses confirmed that dietary lipids were incorporated into both ovarian and muscle lipids during all three stages and revealed that ovarian lipids were more affected than muscle lipids during vitellogenesis. Arachidonic acid (ARA) was incorporated into ovarian lipids at the highest rate of all fatty acids examined with the greatest uptake observed during the cortical alveolus and lipid droplet stages of development. Docosahexaenoic acid (DHA) was incorporated into ovarian lipids at the next highest rate with the greatest uptake observed during the lipid droplet stage of development. The presence of an ovary specific, fatty acid transfer mechanism is proposed. Results from this study demonstrate the ability to greatly alter the fatty acid composition of ovarian lipids through a dietary change during secondary oocyte growth and may be of great interest to producers of farmed salmon and salmon broodstock programs. Published by Elsevier Inc.

Up-regulation of CD44 in the development of metastasis, recurrence and drug resistance of ovarian cancer

PubMed Central

Gao, Yan; Foster, Rosemary; Yang, Xiaoqian; Feng, Yong; Shen, Jacson K.; Mankin, Henry J.; Hornicek, Francis J.; Amiji, Mansoor M.; Duan, Zhenfeng

2015-01-01

The clinical significance of Cluster of Differentiation 44 (CD44) remains controversial in human ovarian cancer. The aim of this study is to evaluate the clinical significance of CD44 expression by using a unique tissue microarray, and then to determine the biological functions of CD44 in ovarian cancer. In this study, a unique ovarian cancer tissue microarray (TMA) was constructed with paired primary, metastatic, and recurrent tumor tissues from 26 individual patients. CD44 expression in TMA was assessed by immunohistochemistry. Both the metastatic and recurrent ovarian cancer tissues expressed higher level of CD44 than the patient-matched primary tumor. A significant association has been shown between CD44 expression and both the disease free survival and overall survival. A strong increase of CD44 was found in the tumor recurrence of mouse model. Finally, when CD44 was knocked down, proliferation, migration/invasion activity, and spheroid formation were significantly suppressed, while drug sensitivity was enhanced. Thus, up-regulation of CD44 represents a crucial event in the development of metastasis, recurrence, and drug resistance to current treatments in ovarian cancer. Developing strategies to target CD44 may prevent metastasis, recurrence, and drug resistance in ovarian cancer. PMID:25823654

Up-regulation of CD44 in the development of metastasis, recurrence and drug resistance of ovarian cancer.

PubMed

Gao, Yan; Foster, Rosemary; Yang, Xiaoqian; Feng, Yong; Shen, Jacson K; Mankin, Henry J; Hornicek, Francis J; Amiji, Mansoor M; Duan, Zhenfeng

2015-04-20

The clinical significance of Cluster of Differentiation 44 (CD44) remains controversial in human ovarian cancer. The aim of this study is to evaluate the clinical significance of CD44 expression by using a unique tissue microarray, and then to determine the biological functions of CD44 in ovarian cancer. In this study, a unique ovarian cancer tissue microarray (TMA) was constructed with paired primary, metastatic, and recurrent tumor tissues from 26 individual patients. CD44 expression in TMA was assessed by immunohistochemistry. Both the metastatic and recurrent ovarian cancer tissues expressed higher level of CD44 than the patient-matched primary tumor. A significant association has been shown between CD44 expression and both the disease free survival and overall survival. A strong increase of CD44 was found in the tumor recurrence of mouse model. Finally, when CD44 was knocked down, proliferation, migration/invasion activity, and spheroid formation were significantly suppressed, while drug sensitivity was enhanced. Thus, up-regulation of CD44 represents a crucial event in the development of metastasis, recurrence, and drug resistance to current treatments in ovarian cancer. Developing strategies to target CD44 may prevent metastasis, recurrence, and drug resistance in ovarian cancer.

Pharmacogenetic algorithm for individualized controlled ovarian stimulation (iCOS) in assisted reproductive technology cycles.

PubMed

Roque, Matheus; Bianco, Bianca; Christofolini, Denise M; Cordts, Emerson B; Vilarino, Fabia L; Carvalho, Waldemar; Valle, Marcello; Sampaio, Marcos; Geber, Selmo; Esteves, Sandro C; Barbosa, Caio P

2018-06-14

Controlled ovarian stimulation (COS) is crucial for optimizing in vitro fertilization (IVF) / intracytoplasmic sperm injection (ICSI) success. Multiple factors influence the ovarian response to COS, making predictions about oocyte yields not so straightforward. As a result, the ovarian response may be poor or suboptimal, or even excessive, all of which have negative consequences for the affected patient. There is a group of patients that present with a suboptimal response to COS despite normal biomarkers of ovarian reserve, such as AFC and AMH. These patients have a lower number of retrieved oocytes than what was expected based on their ovarian reserve, thus showing the inadequacy of using only the traditional ovarian reserve biomarkers to predict the ovarian response. Suboptimal response to COS might be related to ovarian sensitivity to exogenous gonadotropins modulated by genetic factors. The understanding of the gene polymorphisms related to reproductive function can help to improve the clinical management of this patient population and to explain some of the individual patient variability in response to COS. The development of a pharmacogenetic approach concerning COS in the context of assisted reproduction seems attractive as it might help to understand the relationship between genetic variants and ovarian response to exogenous gonadotropins. The patient ́s genetic profile could be used to select the most appropriate gonadotropin type, predict the optimal dosage for each drug, develop a cost-effective treatment plan, maximize the success rates, and lastly, decrease the time-to-pregnancy.

Ovarian transposition in young women and fertility sparing.

PubMed

Mossa, B; Schimberni, M; Di Benedetto, L; Mossa, S

2015-09-01

Ovarian transposition is a highly effective surgical procedure used to preserve ovarian function in premenopausal patients with cancers requiring postoperative or primary pelvic radiotherapy. Pelvic irradiation determines severe damage of ovarian DNA and iatrogenic ovarian failure with premature menopause, necessity of long-term hormone replacement therapy and infertility. We conducted an extensive research of the literature in Medline between January 2000 and April 2015 using the key-words "ovarian transposition radiotherapy", "radiotherapy gonadal function", radiotherapy fertility sparing". The population included young women with normal ovarian function affected by cancers that required pelvic radiotherapy. We have examined 32 articles reporting on 1189 women undergoing ovarian transposition. Median age was 32.5 years, follow up was median 48 months. The procedure has been performed in patients less than 40 years of age. Surgery has been achieved by laparotomy or laparoscoy. We have analyzed effects of radiotherapy on ovarian function. The proportion of women treated by ovarian transposition preserved ovarian function was 70%. About 86% of patients did not develop ovarian cysts and in 98-99% of cases did not occur any metastatic disease. Ovarian transposition is associated with significant preservation of ovarian function and a low frequency of complications as cysts and metastasis. In 31% of cases the procedure can fail. Further studies are needed to evaluate the efficacy of ovarian transposition and the follow up. Ovarian transposition should be discussed at the time of cancer diagnosis in every premenopausal woman requiring pelvic radiotherapy.

Proteomics of ovarian cancer: functional insights and clinical applications

DOE PAGES

Elzek, Mohamed A.; Rodland, Karin D.

2015-03-04

In the past decade, there has been an increasing interest in applying proteomics to assist in understanding the pathogenesis of ovarian cancer, elucidating the mechanism of drug resistance, and in the development of biomarkers for early detection of ovarian cancer. Although ovarian cancer is a spectrum of different diseases, the strategies for diagnosis and treatment with surgery and adjuvant therapy are similar across ovarian cancer types, increasing the general applicability of discoveries made through proteomics research. While proteomic experiments face many difficulties which slow the pace of clinical applications, recent advances in proteomic technology contribute significantly to the identification ofmore » aberrant proteins and networks which can serve as targets for biomarker development and individualized therapies. This review provides a summary of the literature on proteomics’ contributions to ovarian cancer research and highlights the current issues, future directions, and challenges. In conclusion, we propose that protein-level characterization of primary lesion in ovarian cancer can decipher the mystery of this disease, improve diagnostic tools, and lead to more effective screening programs.« less

In vitro fertilization surrogate pregnancy in a patient who underwent radical hysterectomy followed by ovarian transposition, lower abdominal wall radiotherapy, and chemotherapy.

PubMed

Steigrad, Stephen; Hacker, Neville F; Kolb, Bradford

2005-05-01

To describe an IVF surrogate pregnancy from a patient who had a radical hysterectomy followed by excision of a laparoscopic port site implantation with ovarian transposition followed by abdominal wall irradiation and chemotherapy, which resulted in premature ovarian failure from which there was partial recovery. Case report. Tertiary referral university women's hospital in Sydney, Australia and private reproductive medicine clinic in California. A 34-year-old woman who underwent laparoscopy for pelvic pain, shortly afterward followed by radical hysterectomy and pelvic lymph node dissection, who subsequently developed a laparoscopic port site recurrence, which was excised in association with ovarian transposition before abdominal wall irradiation and chemotherapy. Modified IVF treatment, transabdominal oocyte retrieval, embryo cryopreservation in Australia, and transfer to a surrogate mother in the United States. Pregnancy. Miscarriage in the second cycle and a twin pregnancy in the fourth cycle. This is the first case report of ovarian stimulation and oocyte retrieval performed on transposed ovaries after a patient developed premature ovarian failure after radiotherapy and chemotherapy with subsequent partial ovarian recovery.

Sex determination and disorders of sex development according to the revised nomenclature and classification in 46,XX individuals.

PubMed

Kousta, Eleni; Papathanasiou, Asteroula; Skordis, Nicos

2010-01-01

There have been considerable advances concerning understanding of the early and later stages of ovarian development; a number of genes have been implicated and their mutations have been associated with developmental abnormalities. The most important genes controlling the initial phase of gonadal development, identical in females and males, are Wilms' tumor suppressor 1 (WT1) and steroidogenic factor 1 (SF1). Four genes are likely to be involved in the subsequent stages of ovarian development (WNT4, DAX1, FOXL2 and RSPO1), but none is yet proven to be the ovarian determining factor. Changes in nomenclature and classification were recently proposed in order to incorporate genetic advances and substitute gender-based diagnostic labels in terminology. The term "disorders of sex development" (DSD) is proposed to substitute the previous term "intersex disorders". Three main categories have been used to describe DSD in the 46,XX individual: 1) disorders of gonadal (ovarian) development: ovotesticular DSD, previously named true hermaphroditism, testicular DSD, previously named XX males, and gonadal dysgenesis; 2) disorders related to androgen excess (congenital adrenal hyperplasia, aromatase deficiency and P450 oxidoreductase deficiency); and 3) other rare disorders. In this mini-review, recent advances concerning development of the genital system in 46,XX individuals and related abnormalities are discussed. Basic embryology of the ovary and molecular pathways determining ovarian development are reviewed, focusing on mutations disrupting normal ovarian development. Disorders of sex development according to the revised nomenclature and classification in 46,XX individuals are summarized, including genetic progress in the field.

76 FR 79620 - Fisheries of the Exclusive Economic Zone Off Alaska; Gulf of Alaska; Proposed 2012 and 2013...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-22

.... Apportionment of trawl PSC limits between the deep-water and shallow-water fisheries, limits for non-exempt... limit from the third season deep-water species fishery allowance for the GOA trawl fisheries to Rockfish... specifications. The draft 2011 SAFE reports indicate that the biomass trend for shallow-water flatfish, deep...

77 FR 72995 - Fisheries of the Exclusive Economic Zone Off Alaska; Other Flatfish, Other Rockfish, Pacific...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-07

....S.C. 1801, et seq. Dated: December 3, 2012. Emily H. Menashes, Deputy Director, Office of... search. Locate the document you wish to comment on from the resulting list and click on the ``Submit a... Management Act. Regulations governing fishing by U.S. vessels in accordance with the FMP appear at subpart H...

77 FR 72297 - Fisheries of the Exclusive Economic Zone Off Alaska; Gulf of Alaska; Proposed 2013 and 2014...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-05

... from http://www.regulations.gov or from the Alaska Region Web site at http://alaskafisheries.noaa.gov...) at 605 West 4th Avenue, Suite 306, Anchorage, AK 99501, phone 907-271-2809, or from the Council's Web... biomass trends for the following species are relatively stable: shallow-water flatfish, deep-water...

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

PubMed

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

2015-12-01

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

A Mouse Model to Investigate Postmenopausal Biology as an Etiology of Ovarian Cancer Risk

DTIC Science & Technology

2007-11-01

1 mucinous adenocarcinomas 3 clear-cell carcinomas 1 malignant mixed mesodermal tumor 3 metastatic ovarian carcinomas 5 undifferentiated carcinomas 2...serous LMP tumors 2 mucinous LMP tumors 1 benign serous cystadenoma Ovarian tumor blocks 38 18 serous adenocarcinomas 5 mucinous adenocarcinomas 2...endometrioid adenocarcinomas 3 clear cell carcinomas 6 serous LMP 3 mucinous LMP 1 benign fibrous cystadenoma MMPs IN EARLY OVARIAN CANCER DEVELOPMENT

Role of Fallopian Tubes in the Development of Ovarian Cancer.

PubMed

Corzo, Camila; Iniesta, Maria D; Patrono, Maria Guadalupe; Lu, Karen H; Ramirez, Pedro T

2017-02-01

Ovarian cancer is the leading cause of death from gynecologic malignancy and the fifth cause of cancer death in women in the United States. The most common and lethal histologic subtype of epithelial ovarian cancer is high-grade serous carcinoma (HGSC), which generally presents at an advanced stage. HGSC may be associated with BRCA1 and BRCA2 mutations. Historically, HGSC was believed to originate from the ovarian epithelial cells. However, more recent evidence supports the idea that most ovarian cancers originate in the fallopian tube epithelium in both high-risk women and in the general population. Serous tubal intraepithelial carcinomas may ultimately evolve into ovarian or peritoneal cancer. As a result, prophylactic salpingectomy with conservation of the ovaries has become an increasingly more common practice for premenopausal women undergoing risk-reducing surgery. Because the fallopian tube is now recognized as the most common potential site of origin of ovarian carcinoma, there is ongoing research to explore molecular and genetic factors that may be critical in the development of this disease. Further research is needed to identify novel opportunities for early detection and screening of ovarian cancer with the ultimate goal of increasing overall survival. Copyright © 2016 AAGL. Published by Elsevier Inc. All rights reserved.

Fertility drug use and the risk of ovarian tumors in infertile women: a case-control study.

PubMed

Asante, Albert; Leonard, Phoebe H; Weaver, Amy L; Goode, Ellen L; Jensen, Jani R; Stewart, Elizabeth A; Coddington, Charles C

2013-06-01

To assess the influence of infertility and fertility drugs on risk of ovarian tumors. Case-control study (Mayo Clinic Ovarian Cancer Study). Ongoing academic study of ovarian cancer. A total of 1,900 women (1,028 with ovarian tumors and 872 controls, frequency matched on age and region of residence) who had provided complete information in a self-report questionnaire about history of infertility and fertility drug use. None. Effect of infertility history, use of fertility drugs and oral contraception, and gravidity on the risk of ovarian tumor development, after controlling for potential confounders. Among women who had a history of infertility, use of fertility drugs was reported by 44 (24%) of 182 controls and 38 (17%) of 226 cases. Infertile women who used fertility drugs were not at increased risk of developing ovarian tumors compared with infertile women who did not use fertility drugs; the adjusted odds ratio was 0.64 (95% CI, 0.37, 1.11). The findings were similar when stratified by gravidity and when analyzed separately for borderline versus invasive tumors. We found no statistically significant association between fertility drug use and risk of ovarian tumors. Further larger, prospective studies are needed to confirm this observation. Published by Elsevier Inc.

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

PubMed Central

Barbieri, Federica; Bajetto, Adriana; Florio, Tullio

2010-01-01

Ovarian cancer is the most common type of gynecologic malignancy. Despite advances in surgery and chemotherapy, the survival rate is still low since most ovarian cancers relapse and become drug-resistant. Chemokines are small chemoattractant peptides mainly involved in the immune responses. More recently, chemokines were also demonstrated to regulate extra-immunological functions. It was shown that the chemokine network plays crucial functions in the tumorigenesis in several tissues. In particular the imbalanced or aberrant expression of CXCL12 and its receptor CXCR4 strongly affects cancer cell proliferation, recruitment of immunosuppressive cells, neovascularization, and metastasization. In the last years, several molecules able to target CXCR4 or CXCL12 have been developed to interfere with tumor growth, including pharmacological inhibitors, antagonists, and specific antibodies. This chemokine ligand/receptor pair was also proposed to represent an innovative therapeutic target for the treatment of ovarian cancer. Thus, a thorough understanding of ovarian cancer biology, and how chemokines may control these different biological activities might lead to the development of more effective therapies. This paper will focus on the current biology of CXCL12/CXCR4 axis in the context of understanding their potential role in ovarian cancer development. PMID:20049170

Improving efficacy of metastatic tumor segmentation to facilitate early prediction of ovarian cancer patients' response to chemotherapy

NASA Astrophysics Data System (ADS)

Danala, Gopichandh; Wang, Yunzhi; Thai, Theresa; Gunderson, Camille C.; Moxley, Katherine M.; Moore, Kathleen; Mannel, Robert S.; Cheng, Samuel; Liu, Hong; Zheng, Bin; Qiu, Yuchen

2017-02-01

Accurate tumor segmentation is a critical step in the development of the computer-aided detection (CAD) based quantitative image analysis scheme for early stage prognostic evaluation of ovarian cancer patients. The purpose of this investigation is to assess the efficacy of several different methods to segment the metastatic tumors occurred in different organs of ovarian cancer patients. In this study, we developed a segmentation scheme consisting of eight different algorithms, which can be divided into three groups: 1) Region growth based methods; 2) Canny operator based methods; and 3) Partial differential equation (PDE) based methods. A number of 138 tumors acquired from 30 ovarian cancer patients were used to test the performance of these eight segmentation algorithms. The results demonstrate each of the tested tumors can be successfully segmented by at least one of the eight algorithms without the manual boundary correction. Furthermore, modified region growth, classical Canny detector, and fast marching, and threshold level set algorithms are suggested in the future development of the ovarian cancer related CAD schemes. This study may provide meaningful reference for developing novel quantitative image feature analysis scheme to more accurately predict the response of ovarian cancer patients to the chemotherapy at early stage.

Light-sheet microscopy for quantitative ovarian folliculometry

NASA Astrophysics Data System (ADS)

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

2017-02-01

Determination of ovarian status and follicle monitoring are common methods of diagnosing female infertility. We evaluated the suitability of selective plane illumination microscopy (SPIM) for the study of ovarian follicles. Owing to the large field of view and fast acquisition speed of our newly developed SPIM system, volumetric image stacks from entire intact samples of pig ovaries have been rendered demonstrating clearly discernible follicular features like follicle diameters (70 μm - 2.5 mm), size of developing Cumulus oophorus complexes (COC ) (40 μm - 110 μm), and follicular wall thicknesses (90 μm-120 μm). The observation of clearly distinguishable COCs protruding into the follicular antrum was also shown possible, and correlation with the developmental stage of the follicles was determined. Follicles of all developmental stages were identified, and even the small primordial follicle clusters forming the egg nest could be observed. The ability of the system to non-destructively generate sub-cellular resolution 3D images of developing follicles, with excellent image contrast and high throughput capacity compared to conventional histology, suggests that it can be used to monitor follicular development and identify structural abnormalities indicative of ovarian ailments. Accurate folliculometric measurements provided by SPIM images can immensely help the understanding of ovarian physiology and provide important information for the proper management of ovarian diseases.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Elzek, Mohamed A.; Rodland, Karin D.

In the past decade, there has been an increasing interest in applying proteomics to assist in understanding the pathogenesis of ovarian cancer, elucidating the mechanism of drug resistance, and in the development of biomarkers for early detection of ovarian cancer. Although ovarian cancer is a spectrum of different diseases, the strategies for diagnosis and treatment with surgery and adjuvant therapy are similar across ovarian cancer types, increasing the general applicability of discoveries made through proteomics research. While proteomic experiments face many difficulties which slow the pace of clinical applications, recent advances in proteomic technology contribute significantly to the identification ofmore » aberrant proteins and networks which can serve as targets for biomarker development and individualized therapies. This review provides a summary of the literature on proteomics’ contributions to ovarian cancer research and highlights the current issues, future directions, and challenges. In conclusion, we propose that protein-level characterization of primary lesion in ovarian cancer can decipher the mystery of this disease, improve diagnostic tools, and lead to more effective screening programs.« less

Ovarian developmental variation in the primitively eusocial wasp Ropalidia marginata suggests a gateway to worker ontogeny and the evolution of sociality.

PubMed

Shukla, Shantanu; Chandran, Swarnalatha; Gadagkar, Raghavendra

2013-01-15

Social insects are characterized by reproductive caste differentiation of colony members into one or a small number of fertile queens and a large number of sterile workers. The evolutionary origin and maintenance of such sterile workers remains an enduring puzzle in insect sociobiology. Here, we studied ovarian development in over 600 freshly eclosed, isolated, virgin female Ropalidia marginata wasps, maintained in the laboratory. The wasps differed greatly both in the time taken to develop their ovaries and in the magnitude of ovarian development despite having similar access to resources. All females started with no ovarian development at day zero, and the percentage of individuals with at least one oocyte at any stage of development increased gradually across age, reached 100% at 100 days and decreased slightly thereafter. Approximately 40% of the females failed to develop ovaries within the average ecological lifespan of the species. Age, body size and adult feeding rate, when considered together, were the most important factors governing ovarian development. We suggest that such flexibility and variation in the potential and timing of reproductive development may physiologically predispose females to accept worker roles and thus provide a gateway to worker ontogeny and the evolution of sociality.

Identifying Fishes through DNA Barcodes and Microarrays.

PubMed

Kochzius, Marc; Seidel, Christian; Antoniou, Aglaia; Botla, Sandeep Kumar; Campo, Daniel; Cariani, Alessia; Vazquez, Eva Garcia; Hauschild, Janet; Hervet, Caroline; Hjörleifsdottir, Sigridur; Hreggvidsson, Gudmundur; Kappel, Kristina; Landi, Monica; Magoulas, Antonios; Marteinsson, Viggo; Nölte, Manfred; Planes, Serge; Tinti, Fausto; Turan, Cemal; Venugopal, Moleyur N; Weber, Hannes; Blohm, Dietmar

2010-09-07

International fish trade reached an import value of 62.8 billion Euro in 2006, of which 44.6% are covered by the European Union. Species identification is a key problem throughout the life cycle of fishes: from eggs and larvae to adults in fisheries research and control, as well as processed fish products in consumer protection. This study aims to evaluate the applicability of the three mitochondrial genes 16S rRNA (16S), cytochrome b (cyt b), and cytochrome oxidase subunit I (COI) for the identification of 50 European marine fish species by combining techniques of "DNA barcoding" and microarrays. In a DNA barcoding approach, neighbour Joining (NJ) phylogenetic trees of 369 16S, 212 cyt b, and 447 COI sequences indicated that cyt b and COI are suitable for unambiguous identification, whereas 16S failed to discriminate closely related flatfish and gurnard species. In course of probe design for DNA microarray development, each of the markers yielded a high number of potentially species-specific probes in silico, although many of them were rejected based on microarray hybridisation experiments. None of the markers provided probes to discriminate the sibling flatfish and gurnard species. However, since 16S-probes were less negatively influenced by the "position of label" effect and showed the lowest rejection rate and the highest mean signal intensity, 16S is more suitable for DNA microarray probe design than cty b and COI. The large portion of rejected COI-probes after hybridisation experiments (>90%) renders the DNA barcoding marker as rather unsuitable for this high-throughput technology. Based on these data, a DNA microarray containing 64 functional oligonucleotide probes for the identification of 30 out of the 50 fish species investigated was developed. It represents the next step towards an automated and easy-to-handle method to identify fish, ichthyoplankton, and fish products.

New models of hematogenous ovarian cancer metastasis demonstrate preferential spread to the ovary and a requirement for the ovary for abdominal dissemination

PubMed Central

Coffman, Lan G; Burgos-Ojeda, Daniela; Wu, Rong; Cho, Kathleen; Bai, Shoumei; Buckanovich, Ronald J

2016-01-01

Emerging evidence suggest that many high grade serous ‘ovarian’ cancers (HGSOC) start in the fallopian tube. Cancer cells are then recruited to the ovary and then spread diffusely through the abdomen. The mechanism of ovarian cancer spread was thought to be largely due to direct shedding of tumor cells into the peritoneal cavity with vascular spread being of limited importance. Recent work challenges this dogma, suggesting hematogenous spread of ovarian cancer may play a larger role in ovarian cancer cell metastasis than previously thought. One reason the role of vascular spread of ovarian cancer has not been fully elucidated is the lack of easily accessible models of vascular ovarian cancer metastasis. Here we present three metastatic models of ovarian cancer which confirm the ability of ovarian cancer to hematogenously spread. Strikingly, we observe a high rate of metastasis to the ovary with the development of ascites in these models. Interestingly, oophorectomy resulted in a complete loss of peritoneal metastases and ascites. Taken together our data indicates that hematogenously disseminated HGSOC cells have a unique tropism for the ovary and that hematogenous spread in ovarian cancer may be more common than appreciated. Furthermore our studies support a critical role for the ovary in promoting HGSOC cell metastasis to the abdomen. The models developed here represent important new tools to evaluate both the mechanism of cancer cell recruitment to the ovary and to understand and target key steps in ovarian cancer metastasis. PMID:27083386

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

PubMed

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

2017-02-01

Successful reproduction is the result of a myriad interactions in which the ovary and the ovarian follicular reserve play a fundamental role. At present, women who delay maternity until after 30 years of age have a decreased fertility rate due to various causes, including damaged follicles and a reduction in the reserve pool of follicles. Therefore, the period just prior to menopause, also known as the subfertile period, is important. The possibility of modulating the follicular pool and the health of follicles during this period to improve fertility is worth exploring. We have developed an animal model to study the ovarian ageing process during this subfertile period to understand the mechanisms responsible for reproductive senescence. In the rat model, we have shown that the sympathetic nervous system participates in regulating the follicular development during ovarian ageing. This article reviews the existing evidence on the presence and functional role of sympathetic nerve activity in regulating the follicular development during ovarian ageing, with a focus on the subfertile period.Free Spanish abstract: A Spanish translation of this abstract is freely available at http://www.reproduction-online.org/content/153/2/R61/suppl/DC1. © 2017 Society for Reproduction and Fertility.

Evidences for involvement of growth hormone and insulin-like growth factor in ovarian development of starry flounder (Platichthys stellatus).

PubMed

Xu, Yongjiang; Wang, Bin; Liu, Xuezhou; Shi, Bao; Zang, Kun

2017-04-01

Although gonadotrophins are major regulators of ovarian function in teleosts and other vertebrates, accumulating evidence indicates that the growth hormone (GH)-insulin-like growth factor (IGF) axis also plays an important role in fish reproduction. As a first step to understand the physiological role of the GH-IGF system in the ovarian development of starry flounder (Platichthys stellatus), the expression profiles of GH and IGF messenger RNAs (mRNAs) and plasma GH, IGF-I, estradiol-17β (E2), and testosterone (T) levels during the ovarian development were investigated. The developmental stages of ovaries were divided into five stages (II, III, IV, V, and VI) by histological analysis. The hepatosomatic index (HSI) and gonadosomatic index (GSI) values increased and peaked at stage IV and stage V, respectively, and then declined at stage VI. Pituitary GH mRNA levels decreased sharply at stage III and raised to top level at stage VI. The hepatic IGF-I mRNA levels ascended to maximum value at stage V and then declined significantly at stage VI. However, the hepatic IGF-II mRNA levels remained stable and increased significantly at stage VI. In contrast, the ovarian IGF-I mRNA levels increased gradually and peaked at stage VI. The ovarian IGF-II mRNA levels were initially stable and increased significantly at stage V until the top level at stage VI. Consistent with the pituitary GH mRNA levels, plasma GH levels reduced sharply at stage III and remained depressed until stage V and then raised remarkably at stage VI. Plasma IGF-I level peaked at stage V and then declined to initial level. Plasma E2 level peaked at stage IV and then dramatically descended to the basal level. Plasma T level peaked at stage V and then declined significantly back to the basal level. Based on statistical analysis, significant positive correlations between hepatic IGF-I mRNA and GSI, ovarian IGF-II mRNA and hepatic IGF-II mRNA, ovarian IGF-I mRNA and ovarian IGF-II mRNA, and plasma IGF-I and plasma T were observed, respectively. These results suggest that the GH-IGF system may be involved in the ovarian development of starry flounder; GH and IGFs appear to play distinct roles in the regulation of the ovarian development in paracrine/autocrine manners. These findings extend our knowledge of the roles of the GH-IGF axis on reproduction regulation in fish.

Association between average daily television viewing time and the incidence of ovarian cancer: findings from the Japan Collaborative Cohort Study.

PubMed

Ukawa, Shigekazu; Tamakoshi, Akiko; Mori, Mitsuru; Ikehara, Satoyo; Shirakawa, Toru; Yatsuya, Hiroshi; Iso, Hiroyasu

2018-02-01

Seventy-five percent of epidemiological studies have reported that sedentary behavior is associated with ovarian cancer incidence. Although Japan has one of the most sedentary populations, with median sitting times of 7 h/day, this association has not been investigated. This study aimed to elucidate the association between average daily television (TV) viewing time, which is a major sedentary behavior, and the incidence of ovarian cancer in a large-scale nationwide cohort study in Japan. A total of 34,758 female participants aged 40-79 years without a history of cancer at baseline were included in the study. The inverse probability weighted competing risk model was used to calculate the hazard ratio (HR) and 95% confidence interval (CI) for the incidence of ovarian cancer. During a median follow-up of 19.4 years, 59 participants developed ovarian cancer (ICD-10: C56), 2,706 participants developed other types of cancer, and 4,318 participants died. Participants who watched TV for ≥ 5 h/day were more likely to develop ovarian cancer than those who watched TV for < 2 h/day (HR 2.15; 95% CI 1.54-2.99). Our findings suggest that reducing the amount of time spent sedentarily may be beneficial for preventing ovarian cancer.

Phylogeny and expression patterns of two apolipoprotein E genes in the flatfish Senegalese sole.

PubMed

Roman-Padilla, Javier; Rodríguez-Rúa, Ana; Carballo, Carlos; Manchado, Manuel; Hachero-Cruzado, Ismael

2018-02-15

The apolipoprotein E (ApoE) is a key component of several lipoproteins involved in lipid homeostasis. In this study, two cDNA sequences encoding ApoE (referred to as apoEa and apoEb) were characterized in the flatfish Solea senegalensis. The predicted peptides contained conserved structural blocks related with their capacity for lipid binding and lipoprotein receptor interaction. At genomic level, both genes contained five exons and four introns and they were organized into two tandem arrays with apoA-IV gene copies. The phylogenetic analysis clearly separated them into two well-supported clusters that matched with their organization in the genome of teleosts. Whole-mount in situ hybridization located the apoEa signal in the yolk syncytial layer (YSL) of lecitothrophic larval stages (0dph) and in the anterior intestine of exotrophic larvae and benthic fish. In the case of apoEb, hybridization signals were located in the YSL, tail bud, eyes and mouth at 0dph and in the otic vesicle, hindbrain, eyes, pharynx, mouth, heart and intestine at 1dph. In exotrophic larvae, apoEb was ubiquitously expressed in several tissues such as taste buds, brain, mouth, nostril, gills, intestine, liver and around the neuromasts and eyes. Quantification of mRNA levels in pools of whole larvae confirmed distinct expression patterns with a significant reduction of apoEa and an increase of apoEb mRNA levels throughout larval development. Moreover, only apoEa transcripts increased in response to food supply suggesting that this paralog mostly participates in the absorption and transport of dietary lipids and the apoEb in the redistribution of endogenous lipids as well as in neural tissue regeneration. Copyright © 2017 Elsevier B.V. All rights reserved.

Molecular identification and transmission studies of X-cell parasites from Atlantic cod Gadus morhua (Gadiformes: Gadidae) and the northern black flounder Pseudopleuronectes obscurus (Pleuronectiformes: Pleuronectidae)

PubMed Central

2011-01-01

Background Epidermal pseudotumours from Hippoglossoides dubius and Acanthogobius flavimanus in Japan and gill lesions in Limanda limanda from the UK have been shown to be caused by phylogenetically related protozoan parasites, known collectively as X-cells. However, the phylogenetic position of the X-cell group is not well supported within any of the existing protozoan phyla and they are currently thought to be members of the Alveolata. Ultrastructural features of X-cells in fish pseudotumours are somewhat limited and no typical environmental stages, such as spores or flagellated cells, have been observed. The life cycles for these parasites have not been demonstrated and it remains unknown how transmission to a new host occurs. In the present study, pseudobranchial pseudotumours from Atlantic cod, Gadus morhua, in Iceland and epidermal pseudotumours from the northern black flounder, Pseudopleuronectes obscurus, in Japan were used in experimental transmission studies to establish whether direct transmission of the parasite is achievable. In addition, X-cells from Atlantic cod were sequenced to confirm whether they are phylogenetically related to other X-cells and epidermal pseudotumours from the northern black flounder were analysed to establish whether the same parasite is responsible for infecting different flatfish species in Japan. Results Phylogenetic analyses of small subunit ribosomal DNA (SSU rDNA) sequence data from Atlantic cod X-cells show that they are a related parasite that occupies a basal position to the clade containing other X-cell parasites. The X-cell parasite causing epidermal pseudotumours in P. obscurus is the same parasite that causes pseudotumours in H. dubius. Direct, fish to fish, transmission of the X-cell parasites used in this study, via oral feeding or injection, was not achieved. Non-amoeboid X-cells are contained within discrete sac-like structures that are loosely attached to epidermal pseudotumours in flatfish; these X-cells are able to tolerate exposure to seawater. A sensitive nested PCR assay was developed for the sub clinical detection of both parasites and to assist in future life cycle studies. PCR revealed that the parasite in P. obscurus was detectable in non-pseudotumourous areas of fish that had pseudotumours present in other areas of the body. Conclusions The inability to successfully transmit both parasites in this study suggests that either host detachment combined with a period of independent development or an alternate host is required to complete the life cycle for X-cell parasites. Phylogenetic analyses of SSU rDNA confirm a monophyletic grouping for all sequenced X-cell parasites, but do not robustly support their placement within any established protist phylum. Analysis of SSU rDNA from X-cells in Japanese flatfish reveals that the same parasite can infect more than one species of fish. PMID:21299903

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

USDA-ARS?s Scientific Manuscript database

Ovarian cancer, the deadliest of gynecologic cancers, is usually diagnosed at advanced stage due to invalidated screening test and non-specific symptoms presented. Although carboplatin has been popular for treating ovarian cancer for decades, patients eventually develop resistance to this platinum-c...

Activated ovarian endothelial cells promote early follicular development and survival.

PubMed

Kedem, Alon; Aelion-Brauer, Anate; Guo, Peipei; Wen, Duancheng; Ding, Bi-Sen; Lis, Raphael; Cheng, Du; Sandler, Vladislav M; Rafii, Shahin; Rosenwaks, Zev

2017-09-19

New data suggests that endothelial cells (ECs) elaborate essential "angiocrine factors". The aim of this study is to investigate the role of activated ovarian endothelial cells in early in-vitro follicular development. Mouse ovarian ECs were isolated using magnetic cell sorting or by FACS and cultured in serum free media. After a constitutive activation of the Akt pathway was initiated, early follicles (50-150 um) were mechanically isolated from 8-day-old mice and co-cultured with these activated ovarian endothelial cells (AOEC) (n = 32), gel (n = 24) or within matrigel (n = 27) in serum free media for 14 days. Follicular growth, survival and function were assessed. After 6 passages, flow cytometry showed 93% of cells grown in serum-free culture were VE-cadherin positive, CD-31 positive and CD 45 negative, matching the known EC profile. Beginning on day 4 of culture, we observed significantly higher follicular and oocyte growth rates in follicles co-cultured with AOECs compared with follicles on gel or matrigel. After 14 days of culture, 73% of primary follicles and 83% of secondary follicles co-cultured with AOEC survived, whereas the majority of follicles cultured on gel or matrigel underwent atresia. This is the first report of successful isolation and culture of ovarian ECs. We suggest that co-culture with activated ovarian ECs promotes early follicular development and survival. This model is a novel platform for the in vitro maturation of early follicles and for the future exploration of endothelial-follicular communication. In vitro development of early follicles necessitates a complex interplay of growth factors and signals required for development. Endothelial cells (ECs) may elaborate essential "angiocrine factors" involved in organ regeneration. We demonstrate that co-culture with ovarian ECs enables culture of primary and early secondary mouse ovarian follicles.

[Investigation of risk factors for ovarian tumors with the "case-control" method followed by automated prognostication for ovarian oncopathology].

PubMed

Kulinich, S I; Gertsekovich, D A; Cherniak, E V

1994-01-01

The results of questionnaire-based case-control screening for ovarian oncopathology in 478 patients and 478 healthy females are presented. The two groups matched with respect to age and place of residence. An 82.4% effective mathematical decision rule developed. It can be used as a method of early diagnosis of ovarian tumors as well as in formation of groups at high risk.

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

DTIC Science & Technology

2014-10-01

we have received data. Analyses of primary ovarian cancer risk factors (e.g., oral contraceptive use, parity) by histology are complete and a...including (but not limited to) age, oral contraceptive use, tubal ligation, parity, postmenopausal hormone use, family history of ovarian cancer, body mass...of ovarian or breast cancers, menopausal status, postmenopausal hormone use (ever/never, duration, and type), use of oral contraceptives (ever/never

Prevention of Ovarian High Grade Serous Carcinoma by Elucidating Its Early Changes

DTIC Science & Technology

2016-10-01

tissue sections for studies related to study early tumor development in ovarian cancer. This information will be shared with science community. 15...fallopian tube. IMPACT ON SOCIETY BEYOND SCIENCE AND TECHNOLOGY: The findings will help to educate the society about the origins of ovarian...A Team-based Science Approach This project will help to plan the scientific and leadership aspects of the Ovarian Cancer Academy. It will also

Bovine ovarian follicular growth and development correlate with lysophosphatidic acid expression.

PubMed

Sinderewicz, Emilia; Grycmacher, Katarzyna; Boruszewska, Dorota; Kowalczyk-Zięba, Ilona; Staszkiewicz, Joanna; Ślężak, Tomasz; Woclawek-Potocka, Izabela

2018-01-15

The basis of successful reproduction is proper ovarian follicular growth and development. In addition to prostaglandins and vascular endothelial growth factor, a number of novel factors are suggested as important regulators of follicular growth and development: PGES, TFG, CD36, RABGAP1, DBI and BTC. This study focuses on examining the expression of these factors in granulosa and thecal cells that originate from different ovarian follicle types and their link with the expression of lysophosphatidic acid (LPA), known local regulator of reproductive functions in the cow. Ovarian follicles were divided into healthy, transitional, and atretic categories. The mRNA expression levels for PGES, TFG, CD36, RABGAP1, DBI and BTC in granulosa and thecal cells in different follicle types were measured by real-time PCR. The correlations among expression of enzymes synthesizing LPA (autotaxin, phospholipase A2), receptors for LPA and examined factors were measured. Immunolocalization of PGES, TFG, CD36, RABGAP1, DBI and BTC was examined by immunohistochemistry. We investigated follicle-type dependent mRNA expression of factors potentially involved in ovarian follicular growth and development, both in granulosa and thecal cells of bovine ovarian follicles. Strong correlations among receptors for LPA, enzymes synthesizing LPA, and the examined factors in healthy and transitional follicles were observed, with its strongest interconnection with TFG, DBI and RABGAP1 in granulosa cells, and TFG in thecal cells; whereas no correlations in atretic follicles were detected. A greater number of correlations were found in thecal cells than in granulosa cells as well as in healthy follicles than in transitional follicles. These data indicate the role of LPA in the growth, development and physiology of the bovine ovarian follicle. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of HIF-1a/VEGF signaling pathway on plasma progesterone and ovarian prostaglandin F₂a secretion during luteal development of pseudopregnant rats.

PubMed

Pan, X Y; Zhang, Z H; Wu, L X; Wang, Z C

2015-08-03

The corpus luteum is a temporary endocrine structure in mammals that plays an important role in the female reproductive cycle and is formed from a ruptured and ovulated follicle with rapid angiogenesis. Vascular endothelial growth factor (VEGF) is thought to be vital in normal and abnormal angiogenesis in the ovary, but the molecular regulation of luteal VEGF expression during corpus luteum development in vivo is still poorly understood at present. Therefore, we examined whether hypoxia-inducible factor-1a (HIF-1a) is induced and regulates VEGF expression and luteal function in vivo using a pseudopregnant rat model treated with a small-molecule inhibitor of HIF-1a, echinomycin. Corpus luteum development in the pseudopregnant rat ovary was determined after measuring plasma progesterone concentration and ovarian prostaglandin F2a content to reflect changes in HIF-1a and VEGF on different days of this developmental process. At day 7, the corpus luteum was formed and the expression of HIF- 1a/VEGF reached a maximum, while a significant decrease in HIF-1a/ VEGF expression was observed when luteolysis occurred at day 13. Additionally, echinomycin blocked luteal development by inhibiting VEGF expression mediated by HIF-1a and following luteal function by detecting the progesterone changes at day 7. These results demonstrated that HIF-1a-mediated VEGF expression might be an important mechanism regulating ovarian luteal development in mammals in vivo, which may provide new strategies for fertility control and for treating some types of ovarian dysfunction, such as polycystic ovarian syndrome, ovarian hyperstimulation syndrome, and ovarian neoplasia.

Progesterone signaling mediated through progesterone receptor membrane component-1 in ovarian cells with special emphasis on ovarian cancer.

PubMed

Peluso, John J

2011-08-01

Various ovarian cell types including granulosa cells and ovarian surface epithelial cells express the progesterone (P4) binding protein, progesterone receptor membrane component-1 (PGRMC1). PGRMC1 is also expressed in ovarian tumors. PGRMC1 plays an essential role in promoting the survival of both normal and cancerous ovarian cell in vitro. Given the clinical significance of factors that regulate the viability of ovarian cancer, this review will focus on the role of PGRMC1 in ovarian cancer, while drawing insights into the mechanism of PGRMC1's action from cell lines derived from healthy ovaries as well as ovarian tumors. Studies using PGRMC1siRNA demonstrated that P4's ability to inhibit ovarian cells from undergoing apoptosis in vitro is dependent on PGRMC1. To confirm the importance of PGRMC1, the ability of PGRMC1-deplete ovarian cancer cell lines to form tumors in intact nude mice was assessed. Compared to PGRMC1-expressing ovarian cancer cells, PGRMC1-deplete ovarian cancer cells formed tumors in fewer mice (80% compared to 100% for controls). Moreover, the number of tumors derived from PGRMC1-deplete ovarian cancer cells was 50% of that observed in controls. Finally, the tumors that formed from PGRMC1-deplete ovarian cancer cells were about a fourth the size of tumors derived from ovarian cancer cells with normal levels of PGRMC1. One reason for PGRMC1-deplete tumors being smaller is that they had a poorly developed microvasculature system. How PGRMC1 regulates cell viability and in turn tumor growth is not known but part of the mechanism likely involves the regulation of genes that promote cell survival and inhibit apoptosis. Copyright © 2011 Elsevier Inc. All rights reserved.

75 FR 11749 - Fisheries of the Exclusive Economic Zone Off Alaska; Gulf of Alaska; Final 2010 and 2011 Harvest...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-12

... TACs for 2010 and 2011 that are equal to ABCs for pollock, deep-water flatfish, rex sole, sablefish... recommended TACs for 2010 and 2011 that are less than the ABCs for Pacific cod, flathead sole, shallow-water... that the sum of all State and Federal water Pacific cod removals from the GOA not exceed ABC...

77 FR 56798 - Fisheries of the Exclusive Economic Zone Off Alaska; Revise Maximum Retained Amounts for...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-14

... 709 West 9th Street, Room 420A, Juneau, AK. Comments must be submitted by one of the above methods to... the GOA. In 1997, NMFS increased the MRAs for pollock and Pacific cod from zero to 5 percent when... arrowtooth flounder fishery from zero to 20 percent for deep-water flatfish, rex sole, flathead sole, shallow...

Trophodynamic linkage between river runoff and coastal fishery yield elucidated by stable isotope data in the Gulf of Lions (NW Mediterranean).

PubMed

Darnaude, Audrey M; Salen-Picard, Chantal; Polunin, Nicholas V C; Harmelin-Vivien, Mireille L

2004-02-01

The link between climate-driven river runoff and sole fishery yields observed in the Gulf of Lions (NW Mediterranean) was analysed using carbon- and nitrogen stable isotopes along the flatfish food webs. Off the Rhone River, the main terrestrial (river POM) and marine (seawater POM) sources of carbon differed in delta(13)C (-26.11 per thousand and -22.36 per thousand, respectively). Surface sediment and suspended POM in plume water exhibited low delta(13)C (-24.38 per thousand and -24.70 per thousand, respectively) that differed more from the seawater POM than from river POM, demonstrating the dominance of terrestrial material in those carbon pools. Benthic invertebrates showed a wide range in delta(15)N (mean 4.30 per thousand to 9.77 per thousand ) and delta(13)C (mean -23.81 per thousand to -18.47 per thousand ), suggesting different trophic levels, diets and organic sources. Among the macroinvertebrates, the surface (mean delta(13)C -23.71 per thousand ) and subsurface (mean delta(13)C -23.81 per thousand ) deposit-feeding polychaetes were particularly (13)C depleted, indicating that their carbon was mainly derived from terrestrial material. In flatfish, delta(15)N (mean 9.42 to 10.93 per thousand ) and delta(13)C (mean -19.95 per thousand to -17.69 per thousand ) varied among species, indicating differences in food source and terrestrial POM use. A significant negative correlation was observed between the percentage by weight of polychaetes in the diet and the delta(13)C of flatfish white muscle. Solea solea (the main polychaete feeder) had the lowest mean delta(13)C, Arnoglossus laterna and Buglossidium luteum (crustacean, mollusc and polychaete feeders) had intermediate values, and Solea impar (mollusc feeder) and Citharus linguatula (crustacean and fish feeder) exhibited the highest delta(13)C. Two different benthic food webs were thus identified off the Rhone River, one based on marine planktonic carbon and the other on the terrestrial POM carried by the river. Deposit-feeding polychaetes were responsible for the main transfer of terrestrial POM to upper trophic levels, linking sole population dynamics to river runoff fluctuations.

Imaging the ovary.

PubMed

Feng, Yi; Tamadon, Amin; Hsueh, Aaron J W

2018-05-01

During each reproductive cycle, the ovary exhibits tissue remodelling and cyclic vasculature changes associated with hormonally regulated folliculogenesis, follicle rupture, luteal formation and regression. However, the relationships among different types of follicles and corpora lutea are unclear, and the role of ovarian vasculature in folliculogenesis and luteal dynamics has not been extensively investigated. Understanding of ovarian physiology and pathophysiology relies upon elucidation of ovarian morphology and architecture. This paper summarizes the literature on traditional approaches to the imaging of ovarian structures and discusses recent advances in ovarian imaging. Traditional in-vivo ultrasound, together with histological and electron microscopic approaches provide detailed views of the ovary at organ, tissue and molecular levels. However, in-vivo imaging is limited to antral and larger follicles whereas histological imaging is mainly two-dimensional in nature. Also discussed are emerging approaches in the use of near-infrared fluorophores to image follicles in live animals to detect preantral follicles as well as visualizing ovarian structures using CLARITY in fixed whole ovaries to elucidate three-dimensional interrelationships among follicles, corpora lutea and ovarian vasculature. Advances in ovarian imaging techniques provide new understanding of ovarian physiology and allow for the development of better tools to diagnose ovarian pathophysiology. Copyright © 2018 Reproductive Healthcare Ltd. All rights reserved.

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 influence either the initial setting of ovarian reserve during development or the trajectory of ovarian reserve during adult life. For example, exposure to compounds in cigarette smoke may accelerate loss of ovarian reserve in smokers leading to diminished ovarian reserve, earlier age at last child and earlier menopause. Socioenocomic factors are clearly associated with age at natural menopause, with correlations with economic status and education level. However, such effects in western societies are in general small, and the underlying mechanisms remain unclear. CONCLUSIONS Exposure to many environmental compounds, particularly to those that leach from plastics and other synthetic materials, is commonplace in modern societies to the extent that many are found at measurable concentrations in body fluids within most of the population. Relating fluid levels of individual compounds to parameters reflecting ovarian reserve in selected populations appears to be an effective way forward and, indeed, some early-stage findings do show some cause for concern. There is a pressing need for the development of practical advice enabling women to minimize their intake of AHR/ER ligands, perhaps through dietary/cosmetic choices or improved food packaging.

Models of ovarian cancer metastasis: Murine models

PubMed Central

Šale, Sanja; Orsulic, Sandra

2008-01-01

Mice have mainly been used in ovarian cancer research as immunodeficient hosts for cell lines derived from the primary tumors and ascites of ovarian cancer patients. These xenograft models have provided a valuable system for pre-clinical trials, however, the genetic complexity of human tumors has precluded the understanding of key events that drive metastatic dissemination. Recently developed immunocompetent, genetically defined mouse models of epithelial ovarian cancer represent significant improvements in the modeling of metastatic disease. PMID:19337569

Fertility drugs and ovarian cancer.

PubMed

Ali, Aus Tariq

2017-06-20

The aetiology of ovarian cancer is multifactorial with both endogenous and exogenous risk factors playing an important role. The exact pathogenesis of ovarian cancer is still not well understood, despite the number of hypotheses published. Due to an increase in the number of women using fertility drugs, much attention has been focused on the long-term health effects of such drugs. Although fertility drugs facilitate the ovulation process, it is however associated with a significant increase in hormone concentrations, placing exposed women at increased risk of gynaecological cancer. Many clinical and epidemiological studies have examined the association between fertility drugs and ovarian cancer risk. Results from these studies have been contradictory, as some studies have reported an increased risk of ovarian cancer while others reported no increased risk. Nevertheless, recent studies have shown that women who used fertility drugs and did not conceive had a higher risk of developing ovarian cancer, compared to women who used fertility drugs and conceived and delivered successfully. This review discusses the effect of fertility drugs on the risk of developing ovarian cancer, providing details on four possible scenarios associated with fertility treatment. In addition, the limitations of previous studies and their impact on our understanding of the association between fertility drugs and ovarian cancer also have been highlighted. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Epigenetic down-regulated DDX10 promotes cell proliferation through Akt/NF-κB pathway in ovarian cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gai, Muhuizi; Bo, Qifang; Qi, Lixia, E-mail: lixiaqi_dph@sina.com

Ovarian cancer contributes to the majority of ovarian cancer, while the molecular mechanisms remain elusive. Recently, some DEAD box protein 1 has been reported play a tumor suppressor role in ovarian cancer progression. However, the functions of DEAD box protein (DDX) members in ovarian cancer development remain largely unknown. In current study, we retrieved GEO databases and surprisingly found that DDX10 is significantly down-regulated in ovarian cancer tissues compared with normal ovary. These findings suggest that DDX10 might also play a suppressive role in ovarian cancer. We then validated the down-regulated expression pattern of DDX10 in fresh ovarian cancer tissues.more » Furthermore, both loss- and gain-functions assays reveal that the down-regulated DDX10 could promote ovarian cancer proliferation in vitro and the xenograft subcutaneous tumor formation assays confirmed these findings in vivo. In addition, we found that DDX10 is epigenetic silenced by miR-155-5p in ovarian cancer. Moreover, we further preliminary illustrated that down-regulated DDX10 promotes ovarian cancer cell proliferation through Akt/NF-κB pathway. Taken together, in current study, we found a novel tumor suppressor, DDX10, is epigenetic silenced by miR-155-5p in ovarian cancer, and the down-regulated expression pattern of DDX10 promotes ovarian cancer proliferation through Akt/NF-κB pathway. Our findings shed the light that DDX families might be a novel for ovarian cancer treatment. - Highlights: • A novel DEAD box protein, DDX10 is significantly down-regulated in ovarian cancer tissues. • Down-regulated DDX10 promotes ovarian cancer cell proliferation and growth both in vitro and in vivo. • miR-155-5p is highly expressed in ovarian cancer tissues and epigenetically targets DDX10. • DDX10 and miR-155-5p regulates Akt/p65 axis in ovarian cancer cells.« less

Current state of biomarker development for clinical application in epithelial ovarian cancer

PubMed Central

Moore, Richard G.; MacLaughlan, Shannon; Bast, Robert C.

2011-01-01

Each year in the United States over 15,000 women die of epithelial ovarian cancer (EOC)and 22,000 are diagnosed with the disease. The incidence of ovarian cancer has remained stable over the past decade however, survival rates have improved steadily. Increases in survival rates can be attributed to the advances in surgical management, development of effective cytotoxic drugs and the route of administration of chemotherapy. Ovarian cancer survival rates could also be improved through screening and early detection. Disappointingly, effective screening methods have not been established and continue to be elusive. Historically the goal of a screening test was to achieve a positive predictive value (PPV) greater than 10% in order be considered cost effective and have an acceptable risk for the population being screened. Despite the inability of currently available screening algorithms to achieve the desired PPV there may be an advantage in producing a stage migration to lower stages at the time of diagnoses, thereby resulting in improved survival. Equally important recent studies have demonstrated that women who have their initial surgery performed by gynecologic oncologists, and women who have their surgeries at centers experienced in the treatment of ovarian cancer have higher survival rates. For these reasons it is essential that all women at high risk for ovarian cancer receive their initial care by gynecologic oncologists and at centers with multidisciplinary teams experienced in the optimal care of ovarian cancer patients. With this in mind, methods that facilitate the accurate triage of women who will ultimately be diagnosed with ovarian cancer could play a significant role in improving survival rates for these patients. This review article will examine the current state of biomarker use in ovarian cancer screening, risk assessment and for monitoring ovarian cancer patients. PMID:19879639

Cox-1 Suppression and Follicle Depletion in the Etiology of Menopause- Associated Ovarian Cancer

DTIC Science & Technology

2008-04-01

follicular function (2). Most oocytes are progressively lost by atresia, or apoptosis (3), and the ovary may develop a number of atrophic features...the risk of ovarian epithelial cancers, by far the most predominant form (14), and cause growth inhibition and apoptosis in ovarian cancer cell lines...1990;4:390-400. 8. Mintz B. Embryological development of primordial germ-cells in the mouse: influence of a new mutation, Wj. J Embryol Exp

Primary Ovarian Insufficiency Induced by Fanconi Anemia E Mutation in a Mouse Model.

PubMed

Fu, Chun; Begum, Khurshida; Overbeek, Paul A

2016-01-01

In most cases of primary ovarian insufficiency (POI), the cause of the depletion of ovarian follicles is unknown. Fanconi anemia (FA) proteins are known to play important roles in follicular development. Using random insertional mutagenesis with a lentiviral transgene, we identified a family with reduced fertility in the homozygous transgenic mice. We identified the integration site and found that the lentivirus had integrated into intron 8 of the Fanconi E gene (Fance). By RT-PCR and in situ hybridization, we found that Fance transcript levels were significantly reduced. The Fance homozygous mutant mice were assayed for changes in ovarian development, follicle numbers and estrous cycle. Ovarian dysplasias and a severe lack of follicles were seen in the mutant mice. In addition, the estrous cycle was disrupted in adult females. Our results suggest that POI has been induced by the Fance mutation in this new mouse model.

Premature ovarian insufficiency in young girls: repercussions on uterine volume and bone mineral density.

PubMed

Bakhsh, Hanadi; Dei, Metella; Bucciantini, Sandra; Balzi, Daniela; Bruni, Vincenzina

2015-01-01

To evaluate biological differences among young subjects with premature ovarian insufficiency (POI) commencing at different stages of life. Retrospective observational study. Careggi University Hospital Participants: One hundred sixty-two females aged between 15 and 29 years with premature ovarian insufficiency. Data were collected as a retrospective chart review of baseline evaluation at diagnosis of premature ovarian insufficiency (POI). About 162 participants were divided into four groups based on gynecological age. Two primary outcome variables (uterine development and bone mineral density (BMD)) were analyzed in terms of differences among groups and in a multivariate logistic regression analysis. Uterine development was clearly jeopardized when estrogen insufficiency started at a very young age. Total body BMD showed significant differences among the four groups studied, clearly corresponding to the duration of ovarian function. Data were discussed in relation to the choice of hormone replacement therapy regimens.

Coffee, tea, and caffeine consumption and risk of epithelial ovarian cancer and borderline ovarian tumors: Results from a Danish case-control study.

PubMed

Gosvig, Camilla F; Kjaer, Susanne K; Blaakær, Jan; Høgdall, Estrid; Høgdall, Claus; Jensen, Allan

2015-01-01

Epidemiological studies that have investigated the association between coffee, tea and caffeine consumption and ovarian cancer risk have produced conflicting results. Furthermore, only few studies have examined the role of coffee and tea consumption separately for borderline ovarian tumors. By use of data from a large Danish population-based case-control study, we examined the risk of ovarian tumors associated with coffee, tea, and caffeine consumption with a particular focus on characterizing risks by tumor behavior and histology. From 1995 through 1999, we included 267 women with ovarian cancer, 115 women with borderline ovarian tumors and 911 randomly selected control women. All women completed a beverage frequency questionnaire with detailed information on coffee and tea consumption. Analyses were performed using multiple logistic regression models. Both coffee (OR = 0.90; 95% CI 0.84-0.97 per cup/day) and total caffeine consumption from coffee and tea combined (OR = 0.93; 95% CI 0.88-0.98 per 100 mg/day) decreased the risk of ovarian cancer. These associations were significant only for the serous and "other" subtypes of ovarian cancer. No relation between tea consumption and ovarian cancer risk was observed. The risk estimates for borderline ovarian tumors resembled those observed for ovarian cancer, but did not reach statistical significance. Our results indicate that coffee consumption and total caffeine consumption from coffee and tea combined is associated with a modest decreased risk of ovarian cancer. However, more biological studies are needed to identify bioactive chemical compounds in coffee that potentially could affect ovarian cancer development.

78 FR 54741 - National Ovarian Cancer Awareness Month, 2013

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-06

..., women with a family history of breast or ovarian cancer, and those who have had certain types of cancer... Proclamation Each September, America calls attention to a deadly disease that affects thousands of women across our country. This year, over 22,000 women will develop ovarian cancer, and more than half that number...

Secondary Primary Malignancy Risk in Patients With Ovarian Cancer in Taiwan: A Nationwide Population-Based Study.

PubMed

Hung, Yi-Ping; Liu, Chia-Jen; Hu, Yu-Wen; Chen, Min-Huang; Li, Chun-Pin; Yeh, Chiu-Mei; Chiou, Tzeon-Jye; Chen, Tzeng-Ji; Yang, Muh-Hwa; Chao, Yee

2015-09-01

To evaluate the incidence of secondary primary malignancy (SPM) in patients with ovarian cancer using a nationwide retrospective population-based dataset. Patients newly diagnosed with ovarian cancer between 1997 and 2010 were identified using Taiwan's National Health Insurance database. Patients with antecedent malignancies were excluded. Standardized incidence ratios (SIRs) for SPM were calculated and compared with the cancer incidence in the general population. Risk factors for cancer development were analyzed using Cox proportional hazard models. Effects of surgery, chemotherapy, and radiotherapy after ovarian cancer diagnosis were regarded as time-dependent variables to prevent immortal time bias. During the 14-year study period (follow-up of 56,214 person-years), 707 cancers developed in 12,127 patients with ovarian cancer. The SIR for all cancers was 2.78 (95% confidence interval 2.58-3.00). SIRs for follow-up periods of >5, 1-5, and <1 year were 1.87, 2.04, and 6.40, respectively. After the exclusion of SPM occurring within 1 year of ovarian cancer diagnosis, SIRs were significantly higher for cancers of the colon, rectum, and anus (2.14); lung and mediastinum (1.58); breast (1.68); cervix (1.65); uterus (7.96); bladder (3.17), and thyroid (2.23); as well as for leukemia (3.98) and others (3.83). Multivariate analysis showed that age ≥ 50 years was a significant SPM risk factor (hazard ratio [HR] 1.60). Different treatments for ovarian cancer, including radiotherapy (HR 2.07) and chemotherapy (HR 1.27), had different impacts on SPM risk. Patients with ovarian cancer are at increased risk of SPM development. Age ≥ 50 years, radiotherapy, and chemotherapy are independent risk factors. Close surveillance of patients at high risk should be considered for the early detection of SPM.

Ovarian sensitivity index is strongly related to circulating AMH and may be used to predict ovarian response to exogenous gonadotropins in IVF

PubMed Central

2011-01-01

Background Serum anti-Mullerian hormone (AMH) is currently considered the best marker of ovarian reserve and of ovarian responsiveness to gonadotropins in in-vitro fertilization (IVF). AMH assay, however, is not available in all IVF Units and is quite expensive, a reason that limits its use in developing countries. The aim of this study is to assess whether the "ovarian sensitivity index" precisely reflects AMH so that this index may be used as a surrogate for AMH in prediction of ovarian response during an IVF cycle. Methods AMH serum levels were measured in 61 patients undergoing IVF with a "long" stimulation protocol including the GnRH agonist buserelin and recombinant follicle-stimulating hormone (rFSH). Patients were divided into four subgroups according to the percentile of serum AMH and their ovarian stimulation was prospectively followed. Ovarian sensitivity index (OSI) was calculated dividing the total administered FSH dose by the number of retrieved oocytes. Results AMH and OSI show a highly significant negative correlation (r = -0.67; p = 0.0001) that is stronger than the one between AMH and the total number of retrieved oocytes and than the one between AMH and the total FSH dose. Conclusions OSI reflects quite satisfactory the AMH level and may be proposed as a surrogate of AMH assay in predicting ovarian responsiveness to FSH in IVF. Being very easy to calculate and costless, its use could be proposed where AMH measurement is not available or in developing countries where limiting costs is of primary importance. PMID:21824441

Screening for ovarian cancer in women with varying levels of risk, using annual tests, results in high recall for repeat screening tests

PubMed Central

2011-01-01

Background We assessed ovarian cancer screening outcomes in women with a positive family history of ovarian cancer divided into a low-, moderate- or high-risk group for development of ovarian cancer. Methods 545 women with a positive family history of ovarian cancer referred to the Ovarian Screening Service at the Royal Marsden Hospital, London from January 2000- December 2008 were included. They were stratified into three risk-groups according to family history (high-, moderate- and low-risk) of developing ovarian cancer and offered annual serum CA 125 and transvaginal ultrasound screening. The high-risk group was offered genetic testing. Results The median age at entry was 44 years. The number of women in the high, moderate and low-risk groups was 397, 112, and 36, respectively. During 2266 women years of follow-up two ovarian cancer cases were found: one advanced stage at her fourth annual screening, and one early stage at prophylactic bilateral salpingo-oophorectomy (BSO). Prophylactic BSO was performed in 138 women (25.3%). Forty-three women had an abnormal CA125, resulting in 59 repeat tests. The re-call rate in the high, moderate and low-risk group was 14%, 3% and 6%. Equivocal transvaginal ultrasound results required 108 recalls in 71 women. The re-call rate in the high, moderate, and low-risk group was 25%, 6% and 17%. Conclusion No early stage ovarian cancer was picked up at annual screening and a significant number of re-calls for repeat screening tests was identified. PMID:22112691

Cytotoxic T cell clones isolated from ovarian tumor-infiltrating lymphocytes recognize multiple antigenic epitopes on autologous tumor cells.

PubMed

Ioannides, C G; Freedman, R S; Platsoucas, C D; Rashed, S; Kim, Y P

1991-03-01

CTL clones were developed from tumor infiltrating lymphocytes (TIL) from the ascites of a patient with ovarian carcinoma by coculture of TIL with autologous tumor cells and subsequent cloning in the presence of autologous tumor cells. These CTL clones expressed preferential cytolytic activity against autologous tumor cells but not against allogeneic ovarian tumor cells and the NK-sensitive cell line K562. The cytolytic activity of these CTL against autologous tumors was inhibited by anti-TCR (WT31 mAb), anti-HLA class I, and anti-CD3 mAb but not by the NK function antibody Leu 11b. Cloning of the autologous tumor cells in vitro revealed that the CTL clones of the ovarian TIL expressed differential abilities to lyse autologous tumor cell clones. The specificity analysis of these autologous tumor specific CTL suggested that they recognize several antigenic determinants present on the ovarian tumor cells. Our results indicate the presence of at least three antigenic epitopes on the tumor cells (designated OVA-1A, OVA-1B, and OVA-1C), one of which (OVA-1C) is unstable. These determinants are present either simultaneously or separately, and six types of ovarian clones can be distinguished on the basis of their expression. These results indicate that CTL of the TIL detect intratumor antigenic heterogeneity. The novel heterogeneity identified within the ovarian tumor cells in this report may be of significance for understanding cellular immunity in ovarian cancer and developing adoptive specific immunotherapeutic approaches in ovarian cancer.

Maternal fructose intake disturbs ovarian estradiol synthesis in rats.

PubMed

Munetsuna, Eiji; Yamada, Hiroya; Yamazaki, Mirai; Ando, Yoshitaka; Mizuno, Genki; Ota, Takeru; Hattori, Yuji; Sadamoto, Nao; Suzuki, Koji; Ishikawa, Hiroaki; Hashimoto, Shuji; Ohashi, Koji

2018-06-01

Recent increases in fructose consumption have raised concerns regarding the potential adverse intergenerational effects, as maternal fructose intake may induce physiological dysfunction in offspring. However, no reports are available regarding the effect of excess maternal fructose on reproductive tissues such as the ovary. Notably, the maternal intrauterine environment has been demonstrated to affect ovarian development in the subsequent generation. Given the fructose is transferred to the fetus, excess fructose consumption may affect offspring ovarian development. As ovarian development and its function is maintained by 17β-estradiol, we therefore investigated whether excess maternal fructose intake influences offspring ovarian estradiol synthesis. Rats received a 20% fructose solution during gestation and lactation. After weaning, offspring ovaries were isolated. Offspring from fructose-fed dams showed reduced StAR and P450(17α) mRNA levels, along with decreased protein expression levels. Conversely, attenuated P450arom protein level was found in the absence of mRNA expression alteration. Consistent with these phenomena, decreased circulating levels of estradiol were observed. Furthermore, estrogen receptor α (ERα) protein levels were also down-regulated. In accordance, the mRNA for progesterone receptor, a transcriptional target of ERα, was decreased. These results suggest that maternal fructose might alter ovarian physiology in the subsequent generation. Copyright © 2018 Elsevier Inc. All rights reserved.

FOXL2 activates P450 aromatase gene transcription: towards a better characterization of the early steps of mammalian ovarian development.

PubMed

Pannetier, Maëlle; Fabre, Stéphane; Batista, Frank; Kocer, Ayhan; Renault, Lauriane; Jolivet, Geneviève; Mandon-Pépin, Béatrice; Cotinot, Corinne; Veitia, Reiner; Pailhoux, Eric

2006-06-01

Previous studies have equated FOXL2 as a crucial actor in the ovarian differentiation process in different vertebrate species. Its transcriptional extinction in the polled intersex syndrome (PIS) leads primarily to a drastic decrease of aromatase (CYP19) expression in the first steps of goat ovarian development. In this study, we provide a better characterization of early ovarian development in goat, and we provide experimental evidence demonstrating that FOXL2 represents a direct transcriptional activator of the CYP19 gene through its ovarian-specific promoter 2. Moreover, the ovarian location of FOXL2 and CYP19 proteins, together with their expression profiles in the female gonads, stress the involvement of FOXL2 co-factor(s) for regulating CYP19 transcription. Expressional analyses show that activin-betaA can be considered as a strong candidate for being one of these FOXL2 co-factors. Finally, we discuss evidence for a role of activin and estrogens in somatic and germinal cell proliferation occurring before germ cell meiosis. This period, of 20 days in goat, seems to have no equivalent in mouse. This species-specific difference could explain the phenotype discrepancy observed between XX goat PIS(-/-) and XX mouse Foxl2(-/-).

Hawaii natural compounds are promising to reduce ovarian cancer deaths.

PubMed

Fei-Zhang, David J; Li, Chunshun; Cao, Shugeng

2016-07-02

The low survival rate of patients with ovarian cancer largely results from the advanced ovarian tumors as well as tumor resistance to chemotherapy, leading to metastasis and recurrence. However, it is missing as to an effective therapeutic approach that focuses on these aspects to prolong progression-free survival and to decrease mortality in ovarian cancer patients. Here, based on our cancer drug discovery studies, we provide prospective insights into the development of a future line of drugs to effectively reduce ovarian cancer deaths. Pathways that increase the probability of cancer, such as the defective Fanconi anemia (FA) pathway, may render cancer cells more sensitive to new drug targeting.

Effects of thermal regime on ovarian maturation and plasma sex steroids in farmed white sturgeon, Acipenser transmontanus

USGS Publications Warehouse

Webb, M.A.H.; Van Eenennaam, J. P.; Feist, G.W.; Linares-Casenave, J.; Fitzpatrick, M.S.; Schreck, C.B.; Doroshov, S.I.

2001-01-01

Recently, commercial aquaculture farms in Northern California have exposed gravid, cultured white sturgeon females to cold water (12 ?? 1??C) throughout the late phase of vitellogenesis and ovarian follicle maturation resulting in improved ovulation rates and egg quality. However, the optimum timing for transfer of broodfish to the cold water and the capacity of transferred broodfish to maintain reproductive competence over an extended time in cold water had not been evaluated. Gravid white sturgeon females that have been raised at water temperatures of 16-20??C were transported to either cold water (12 ?? 1??C; Group 1) in November 1997 or maintained in ambient water temperatures (10-19??C; Group 2) until early spring. In March 1998, half of the fish in Group 2 had regressed ovaries, but the remaining females had intact ovarian follicles and were transported to the cold water. Ovarian follicles and blood were collected from females until they reached the stage of spawning readiness (determined by germinal vesicle position and an oocyte maturation assay) or underwent ovarian regression. Exposure of gravid sturgeon females to ambient water temperatures (14.5 ?? 2.3??C, mean ?? S.D.) from October to March led to a decrease in plasma sex steroids and a high incidence of ovarian regression in fish with a more advanced stage of oocyte development. Transfer of females with intact ovarian follicles to cold water (12 ?? 1??C) in the fall or early spring resulted in normal ovarian development in the majority of females. Holding females in cold water does not seem to override their endogenous reproductive rhythms but extends their capacity to maintain oocyte maturational competence over a longer period of time. A temperature-sensitive phase in ovarian development may occur during the transition from vitellogenic growth to oocyte maturation, and the degree and timing of sensitivity to environmental temperature are dependent on the female's endogenous reproductive rhythm. ?? 2001 Elsevier Science B.V. All Rights reserved.

Regulatory considerations on endpoints in ovarian cancer drug development.

PubMed

Balasubramaniam, Sanjeeve; Kim, Geoffrey S; McKee, Amy E; Pazdur, Richard

2017-07-15

Ovarian cancer remains a disease entity that is responsible for considerable morbidity and mortality among women worldwide. Modern drug research pipelines and accelerated drug development timelines applied to other disease entities have begun to make an impact on treatment options for patients with advanced ovarian cancer, as exemplified by the recent accelerated approval of 2 agents for this disease as the forerunners of a growing number of registrational trials. Regulatory flexibility for this serious and life-threatening condition spurs the consideration of intermediate endpoints for regulatory trial design, including potential applications in the development of newer therapeutic classes such as targeted therapies and immunotherapies for patients with advanced ovarian cancer. Cancer 2017;123:2604-8. © 2017 American Cancer Society. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

Premature ovarian insufficiency: Pathogenesis and management

PubMed Central

Fenton, Anna J.

2015-01-01

The term premature ovarian insufficiency (POI) describes a continuum of declining ovarian function in a young woman, resulting in an earlier than average menopause. It is a term that reflects the variable nature of the condition and is substantially less emotive than the formerly used “premature ovarian failure” which signaled a single event in time. Contrary to the decline in the age of menarche seen over the last 3-4 decades there has been no similar change in the age of menopause. In developed nations, the average age for cessation of menstrual cycles is 50-52 years. The age is younger among women from developing nations. Much has been written about POI despite a lack of good data on the incidence of this condition. It is believed that 1% of women under the age of 40 years and 0.1% under the age of 30 years will develop POI. Research is increasingly providing information about the pathogenesis and treatments are being developed to better preserve ovarian function during cancer treatment and to improve fertility options. This narrative review summarizes the current literature to provide an approach to best practice management of POI. PMID:26903753

Tissue factor expression as a possible determinant of thromboembolism in ovarian cancer

PubMed Central

Uno, K; Homma, S; Satoh, T; Nakanishi, K; Abe, D; Matsumoto, K; Oki, A; Tsunoda, H; Yamaguchi, I; Nagasawa, T; Yoshikawa, H; Aonuma, K

2007-01-01

Ovarian cancer, and clear cell carcinoma in particular, reportedly increases the risk of venous thromboembolism (VTE). However, the mechanisms remain unclear. Tissue factor (TF) supposedly represents a major factor in the procoagulant activities of cancer cells. The present study examined the involvement of TF expression in VTE for patients with ovarian cancer. Subjects comprised 32 consecutive patients (mean age 49.8 years) with histologically confirmed ovarian cancer. Presence of VTE was examined using a combination of clinical features, D-dimer levels and venous ultrasonography. Immunohistochemical analysis was used to evaluate TF expression into 4 degrees. Venous thromboembolism was identified in 10 of the 32 patients (31%), including five of the 11 patients with clear cell carcinoma. Tissue factor expression was detected in cancer tissues from 24 patients and displayed significant correlations with VTE development (P=0.0003), D-dimer concentration (P=0.003) and clear cell carcinoma (P<0.05). Multivariate analysis identified TF expression as an independent predictive factor of VTE development (P<0.05). Tissue factor (TF) expression is a possible determinant of VTE development in ovarian cancer. In particular, clear cell carcinoma may produce excessive levels of TF and is more likely to develop VTE. PMID:17211468

Modulation of ovarian steroidogenesis by adiponectin during delayed embryonic development of Cynopterus sphinx.

PubMed

Anuradha; Krishna, Amitabh

2014-09-01

The aim of present study was to evaluate role of adiponectin in ovarian steroidogenesis during delayed embryonic development of Cynopterus sphinx. This study showed significantly low circulating adiponectin level and a decline in expression of adiponectin receptor 1 (AdipoR1) in the ovary during the period of delayed embryonic development as compared with the normal development. The adiponectin treatment in vivo during the period of delayed development caused significantly increased in circulating progesterone and estradiol levels together with increased expression of AdipoR1 in the ovary. The in vitro study confirmed the stimulatory effect of adiponectin on progesterone synthesis. Both in vivo and in vitro studies showed that the effects of adiponectin on ovarian steroidogenesis were mediated through increased expression of luteinizing hormone-receptor, steroidogenic acute regulatory protein and 3β-hydroxyl steroid dehydrogenase enzyme. The adiponectin treatment may also promote progesterone synthesis by modulating ovarian angiogenesis, cell survival and rate of apoptosis. Copyright © 2014 Elsevier Ltd. All rights reserved.

Role of juvenile hormone and allatotropin on nutrient allocation, ovarian development and survivorship in mosquitoes

PubMed Central

Hernández-Martínez, Salvador; Mayoral, Jaime G.; Li, Yiping; Noriega, Fernando G.

2009-01-01

Teneral reserves are utilized to initiate previtellogenic ovarian development in mosquitoes. Females having emerged with low teneral reserves have reduced juvenile hormone (JH) synthesis and previtellogenic development. We investigated what role JH, allatotropin (AT) and other head-factors play in the regulation of previtellogenic ovarian development and adult survivorship. Factors from the head are essential for corpora allata (CA) activation and reproductive maturation. We have shown that decapitation of females within 9–12 h after adult ecdysis prevented normal development of the previtellogenic follicles; however maximum previtellogenic ovarian development could be induced in decapitated females by topically applying a JH analog. When females were decapitated 12 or more hours after emergence nutritional resources had been committed to ovarian development and survivorship was significantly reduced. To study if allatotropin levels correlated with teneral reserves, we measured AT titers in the heads of two adult phenotypes (large and small females) generated by raising larvae under different nutritional diets. In large mosquitoes AT levels increased to a maximum of 45 fmol in day 4; in contrast, the levels of allatotropin in the heads of small mosquitoes remained below 9 fmol during the 7 days evaluated. These results suggest that only when nutrients are appropriate, factors released from the brain induce the CA to synthesize enough JH to activate reproductive maturation. PMID:17070832

Methoxyphenyl chalcone sensitizes aggressive epithelial cancer to cisplatin through apoptosis induction and cancer stem cell eradication.

PubMed

Su, Yu-Kai; Huang, Wen-Chien; Lee, Wei-Hwa; Bamodu, Oluwaseun Adebayo; Zucha, Muhammad Ary; Astuti, Indwiani; Suwito, Heri; Yeh, Chi-Tai; Lin, Chien-Min

2017-05-01

Current standard chemotherapy for late stage ovarian cancer is found unsuccessful due to relapse after completing the regimens. After completing platinum-based chemotherapy, 70% of patients develop relapse and resistance. Recent evidence proves ovarian cancer stem cells as the source of resistance. Therefore, treatment strategy to target both cancer stem cells and normal stem cells is essential. In this study, we developed a novel chalcone derivative as novel drug candidate for ovarian cancer treatment. We found that methoxyphenyl chalcone was effective to eliminate ovarian cancer cells when given either as monotherapy or in combination with cisplatin. We found that cell viability of ovarian cancer cells was decreased through apoptosis induction. Dephosphorylation of Bcl2-associated agonist of cell death protein was increased after methoxyphenyl chalcone treatment that led to activation of caspases. Interestingly, this drug also worked as a G2/M checkpoint modulator with alternative ways of DNA damage signal-evoking potential that might work to increase response after cisplatin treatment. In addition, methoxyphenyl chalcone was able to suppress autophagic flux and stemness regulator in ovarian spheroids that decreased their survival. Therefore, combination of methoxyphenyl chalcone and cisplatin showed synergistic effects. Taken together, we believe that our novel compound is a promising novel therapeutic agent for effective clinical treatment of ovarian cancer.

Focused glycomic analysis of the N-linked glycan biosynthetic pathway in ovarian cancer

PubMed Central

Abbott, Karen L.; Nairn, Alison V.; Hall, Erica M.; Horton, Marc B.; McDonald, John F.; Moremen, Kelley W.; Dinulescu, Daniela M.; Pierce, Michael

2014-01-01

Epithelial ovarian cancer is the deadliest female reproductive tract malignancy in Western countries. Less than 25% of cases are diagnosed when the cancer is confined, however, pointing to the critical need for early diagnostics for ovarian cancer. Identifying the changes that occur in the glycome of ovarian cancer cells may provide an avenue to develop a new generation of potential biomarkers for early detection of this disease. We performed a glycotranscriptomic analysis of endometrioid ovarian carcinoma using human tissue, as well as a newly developed mouse model that mimics this disease. Our results show that the N-linked glycans expressed in both non-diseased mouse and human ovarian tissues are similar; moreover, malignant changes in the expression of N-linked glycans in both mouse and human endometrioid ovarian carcinoma are qualitatively similar. Lectin reactivity was used as a means for rapid validation of glycan structural changes in the carcinomas that were predicted by the glycotranscriptome analysis. Among several changes in glycan expression noted, the increase of bisected N-linked glycans and the transcripts of the enzyme responsible for its biosynthesis, GnT-III, was the most significant. This study provides evidence that glycotranscriptome analysis can be an important tool in identifying potential cancer biomarkers. PMID:18690643

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.

Ecology and Population Dynamics of Juvenile Dungeness Crab in Grays Harbor Estuary and Adjacent Nearshore Waters of the Southern Washington Coast

DTIC Science & Technology

1989-10-01

77 5.1.2 Models of environmental and density- dependent recruitment ................................................ 80 5.2 Other Population...juvenile Dungeness crabs and flatfish ........................................ 17 Figure 1.6. Seasonal change in bottom temperature and bottom salinity ...to 2+ ............. 120 Figure 6.14. Size dependence of relative size increments per molt (expressed as a fraction of premolt size), as obtained from

Complex movement patterns of greenback flounder (Rhombosolea tapirina) in the Murray River estuary and Coorong, Australia

NASA Astrophysics Data System (ADS)

Earl, Jason; Fowler, Anthony J.; Ye, Qifeng; Dittmann, Sabine

2017-04-01

The greenback flounder Rhombosolea tapirina is a commercially-important flatfish species in southern Australia and New Zealand, whose population dynamics are poorly understood. Acoustic telemetry was used to assess movement patterns and area use for R. tapirina in the Murray River estuary and Coorong, South Australia. Twenty fish (221-313 mm total length) equipped with acoustic transmitters were monitored for up to seven months during a period of high freshwater inflow. Fish were detected over a large part of the system, but showed a strong preference for brackish and near-marine conditions in the inner estuary. Tagged fish exhibited complex movement patterns that differed among individuals, including: (1) within estuary movements; (2) dispersal from the estuary to the sea; and (3) return migrations between the estuary and the sea. A diurnal shift in fine-scale area use was observed in the part of the estuary where residency was highest, with individuals occupying deeper habitats during the day and shallower areas during the night. The results demonstrate the individualistic and often highly transient behaviour of this species and its ability to undertake regular movements over the spatial scale of 10s of km. Understanding such movement patterns can improve effective management of estuarine flatfish populations and ecosystems.

Key role of scale morphology in flatfishes (Pleuronectiformes) in the ability to keep sand

PubMed Central

Spinner, Marlene; Kortmann, Mareike; Traini, Camille; Gorb, Stanislav N.

2016-01-01

Flatfishes bury themselves for camouflage and protection. Whereas species-specific preferences for certain sediments were previously shown, the role of scales in interaction with sediment has not been investigated. Here, scale morphology and sediment friction were examined in four European pleuronectiforms: Limanda limanda, Platichthys flesus, Pleuronectes platessa, and Solea solea. All species had different scale types ranging from cycloid to ctenoid scales. On the blind side, the number of scales is higher and scales have less ctenial spines than on the eye side. The critical angle of sediment sliding (static friction) significantly depended on the grain size and was considerably higher on the eye side. The effect of mucus was excluded by repeated measurements on resin replicas of the skin. Our results demonstrate the impact of scale morphology on sediment interaction and give an insight about the ability of scales to keep sand. Exposed scales and a higher number of ctenial spines on the eye side lead to an increase of friction forces, especially for sediments with a smaller grain size. Our results suggest that the evolution of scales was at least partly driven by their interactions with sediment which confirms the relevance of sediment for the distribution and radiation of Pleuronectiformes. PMID:27199035

Preclinical activity of melflufen (J1) in ovarian cancer.

PubMed

Carlier, Charlotte; Strese, Sara; Viktorsson, Kristina; Velander, Ebba; Nygren, Peter; Uustalu, Maria; Juntti, Therese; Lewensohn, Rolf; Larsson, Rolf; Spira, Jack; De Vlieghere, Elly; Ceelen, Wim P; Gullbo, Joachim

2016-09-13

Ovarian cancer carries a significant mortality. Since symptoms tend to be minimal, the disease is often diagnosed when peritoneal metastases are already present. The standard of care in advanced ovarian cancer consists of platinum-based chemotherapy combined with cytoreductive surgery. Unfortunately, even after optimal cytoreduction and adjuvant chemotherapy, most patients with stage III disease will develop a recurrence. Intraperitoneal administration of chemotherapy is an alternative treatment for patients with localized disease. The pharmacological and physiochemical properties of melflufen, a peptidase potentiated alkylator, raised the hypothesis that this drug could be useful in ovarian cancer and particularily against peritoneal carcinomatosis. In this study the preclinical effects of melflufen were investigated in different ovarian cancer models. Melflufen was active against ovarian cancer cell lines, primary cultures of patient-derived ovarian cancer cells, and inhibited the growth of subcutaneous A2780 ovarian cancer xenografts alone and when combined with gemcitabine or liposomal doxorubicin when administered intravenously. In addition, an intra- and subperitoneal xenograft model showed activity of intraperitoneal administered melflufen for peritoneal carcinomatosis, with minimal side effects and modest systemic exposure. In conclusion, results from this study support further investigations of melflufen for the treatment of peritoneal carcinomatosis from ovarian cancer, both for intravenous and intraperitoneal administration.

Preclinical activity of melflufen (J1) in ovarian cancer

PubMed Central

Viktorsson, Kristina; Velander, Ebba; Nygren, Peter; Uustalu, Maria; Juntti, Therese; Lewensohn, Rolf; Larsson, Rolf; Spira, Jack; De Vlieghere, Elly; Ceelen, Wim P.; Gullbo, Joachim

2016-01-01

Ovarian cancer carries a significant mortality. Since symptoms tend to be minimal, the disease is often diagnosed when peritoneal metastases are already present. The standard of care in advanced ovarian cancer consists of platinum-based chemotherapy combined with cytoreductive surgery. Unfortunately, even after optimal cytoreduction and adjuvant chemotherapy, most patients with stage III disease will develop a recurrence. Intraperitoneal administration of chemotherapy is an alternative treatment for patients with localized disease. The pharmacological and physiochemical properties of melflufen, a peptidase potentiated alkylator, raised the hypothesis that this drug could be useful in ovarian cancer and particularily against peritoneal carcinomatosis. In this study the preclinical effects of melflufen were investigated in different ovarian cancer models. Melflufen was active against ovarian cancer cell lines, primary cultures of patient-derived ovarian cancer cells, and inhibited the growth of subcutaneous A2780 ovarian cancer xenografts alone and when combined with gemcitabine or liposomal doxorubicin when administered intravenously. In addition, an intra- and subperitoneal xenograft model showed activity of intraperitoneal administered melflufen for peritoneal carcinomatosis, with minimal side effects and modest systemic exposure. In conclusion, results from this study support further investigations of melflufen for the treatment of peritoneal carcinomatosis from ovarian cancer, both for intravenous and intraperitoneal administration. PMID:27528037

Origins based clinical and molecular complexities of epithelial ovarian cancer.

PubMed

Muinao, Thingreila; Pal, Mintu; Boruah, Hari Prasanna Deka

2018-06-08

Ovarian cancer is the most lethal of all common gynaecological malignancies in women worldwide. Ovarian cancer comprises of >15 distinct tumor types and subtypes characterized by histopathological features, environmental and genetic risk factors, precursor lesions and molecular events during oncogenesis. Recent studies on gene signatures profiling of different subtypes of ovarian cancer have revealed significant genetic heterogeneity between and within each ovarian cancer histological subtype. Thus, an immense interest have shown towards a more personalized medicine for understanding the clinical and molecular complexities of four major types of epithelial ovarian cancer (serous, endometrioid, clear cell, and mucinous). As such, further in depth studies are needed for identification of molecular signalling network complexities associated with effective prognostication and targeted therapies to prevent or treat metastasis. Therefore, understanding the metastatic potential of primary ovarian cancer and therapeutic interventions against lethal ovarian cancer for the development of personalized therapies is very much indispensable. Consequently, in this review we have updated the key dysregulated genes of four major subtypes of epithelial carcinomas. We have also highlighted the recent advances and current challenges in unravelling the complexities of the origin of tumor as well as genetic heterogeneity of ovarian cancer. Copyright © 2017. Published by Elsevier B.V.

Immunohistochemical localization of HE4 in benign, borderline, and malignant lesions of the ovary.

PubMed

Georgakopoulos, Penelope; Mehmood, Saira; Akalin, Ali; Shroyer, Kenneth R

2012-11-01

Despite advances in the development of novel methods to improve treatment, ovarian carcinoma is still the leading cause of gynecologic cancer death in the United States and other industrialized nations. Improvements in the clinical outcome of ovarian cancer will be achieved if methods can be developed to enable the detection of these tumors at the earliest possible stage. Thus, it is critically important to identify and validate new biomarkers of ovarian cancer. HE4 expression was defined by immunohistochemical analysis of a wide range of benign, borderline, and malignant ovarian lesions, including serous, endometrioid, mucinous, and clear cell lesions of the ovary and in primary tubal carcinomas and the normal fallopian tube. At the cellular level, HE4 was highly expressed in malignant ovarian tumors and in a wide range of benign and borderline ovarian lesions. In addition, HE4 was highly expressed in primary fallopian tube carcinomas and benign fallopian tubal epithelial cells. These results support the conclusion that HE4 is widely expressed in most benign, borderline, and malignant lesions of the ovary and the fallopian tube. The detection of HE4 expression at high levels in some benign lesions and normal tissues suggests that HE4 could have limited specificity as a marker of ovarian or tubal carcinoma. Furthermore, the relatively weak expression that was observed in many ovarian carcinomas indicates that HE4 could fail to detect some cases of primary or recurrent disease.

Metabolomic changes in follicular fluid induced by soy isoflavones administered to rats from weaning until sexual maturity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Wenxiang; Zhang, Wenchang, E-mail: wenchang2002@sina.com; Liu, Jin

Female Wistar rats at 21 days of age were treated with one of three concentrations of soy isoflavones (SIF) (50, 100 or 200 mg/kg body weight, orally, once per day) from weaning until sexual maturity (3 months) in order to evaluate the influence of SIF on ovarian follicle development. After treatment, the serum sex hormone levels and enumeration of ovarian follicles of the ovary were measured. The metabolic profile of follicular fluid was determined using HPLC-MS. Principal component analysis (PCA) and partial least-squares-discriminant analysis (PLS-DA) was used to identify differences in metabolites and reveal useful toxic biomarkers. The results indicatedmore » that modest doses of SIF affect ovarian follicle development, as demonstrated by decreased serum estradiol levels and increases in both ovarian follicle atresia and corpora lutea number in the ovary. SIF treatment-related metabolic alterations in follicular fluid were also found in the PCA and PLS-DA models. The 24 most significantly altered metabolites were identified, including primary sex hormones, amino acids, fatty acids and metabolites involved in energy metabolism. These findings may indicate that soy isoflavones affect ovarian follicle development by inducing metabolomic variations in the follicular fluid. - Highlights: ► Modest doses of soy isoflavones (SIF) do affect ovarian follicle development. ► SIF treatment-related metabolic alterations in follicular fluid were found. ► The 24 most significantly altered metabolites were identified.« less

Expression of motility-related molecule Cdc42 in endometrial tissue in women with adenomyosis and ovarian endometriomata.

PubMed

Goteri, Gaia; Ciavattini, Andrea; Lucarini, Guendalina; Montik, Nina; Filosa, Alessandra; Stramazzotti, Daniela; Biagini, Graziella; Tranquilli, Andrea Luigi

2006-09-01

To evaluate Cdc42 expression in eutopic and ectopic endometrial tissue in patients with adenomyosis and ovarian endometriotic cysts compared with patients without endometriosis. Experimental retrospective study. University hospital. Twenty-four patients with adenomyosis, 19 with ovarian endometriomata, and 9 with fibroids or benign ovarian cysts. Hysterectomy and bilateral oophorectomy. Immunostaining for Cdc42 of eutopic and ectopic endometrial tissues. In eutopic endometrium of patients with adenomyosis and with fibroids or benign ovarian cysts, the intensity of Cdc42 immunostaining was weaker, especially in the specialized stromal cells, compared with cases with ovarian endometriosis (chi(2) test, P=.003). Expression of Cdc42 in eutopic endometrium showed a trend to be higher in the secretory than in the proliferative phase and in patients with ovarian endometriotic cysts compared with patients with adenomyosis (unpaired t test, P=.005), especially in the proliferative phase. An abnormally high expression of Cdc42 in eutopic endometrium in the secretory phase may contribute to the development of ovarian endometriosis, but it does not seem to be involved in the pathogenesis of adenomyosis.

The rise of genomic profiling in ovarian cancer

PubMed Central

Previs, Rebecca A.; Sood, Anil K.; Mills, Gordon B.; Westin, Shannon N.

2017-01-01

Introduction Next-generation sequencing and advances in ‘omics technology have rapidly increased our understanding of the molecular landscape of epithelial ovarian cancers. Areas covered Once characterized only by histologic appearance and clinical behavior, we now understand many of the molecular phenotypes that underlie the different ovarian cancer subtypes. While the current approach to treatment involves standard cytotoxic therapies after cytoreductive surgery for all ovarian cancers regardless of histologic or molecular characteristics, focus has shifted beyond a ‘one size fits all’ approach to ovarian cancer. Expert commentary Genomic profiling offers potentially ‘actionable’ opportunities for development of targeted therapies and a more individualized approach to treatment with concomitant improved outcomes and decreased toxicity. PMID:27828713

Genetically engineered mouse models for epithelial ovarian cancer: are we there yet?

PubMed

Howell, Viive M

2014-03-01

The development of preclinical spontaneous genetically engineered mouse models (GEMMs) requires an understanding of the genetic basis of the human disease. Such robust models have proven invaluable for increasing understanding of human malignancies as well as identifying new biomarkers and testing new therapies for these diseases. While GEMMs have been reported for ovarian cancer, the majority have proven disappointing overall in their recapitulation of paired genetic and histological features especially for serous ovarian epithelial cancer. This review describes GEMMs for ovarian cancer, in particular, high grade serous ovarian cancer and assesses these in light of recent changes in our understanding of the human malignancy. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effects of neonatal litter size and age on ovarian gene expression and follicular development in gilts

USDA-ARS?s Scientific Manuscript database

Gilts raised in small litters have greater ovulation rate, stay in the herd longer and produce more pigs. The objective was to understand how neonatal litter size affects gilt development. The hypothesis is that gilts reared in smaller litters have greater ovarian follicular development. Within 24 h...

Recent Progress in the Diagnosis and Treatment of Ovarian Cancer

PubMed Central

Jelovac, Danijela; Armstrong, Deborah K.

2013-01-01

Epithelial ovarian cancer is the most lethal of the gynecologic malignancies, largely due to the advanced stage at diagnosis in most patients. Screening strategies using ultrasound and the cancer antigen (CA) 125 tumor marker are currently under study and may lower stage at diagnosis but have not yet been shown to improve survival. Women who have inherited a deleterious mutation in the BRCA1 or BRCA2 gene and those with the Lynch syndrome (hereditary nonpolyposis colorectal cancer) have the highest risk of developing ovarian cancer but account for only approximately 10% of those with the disease. Other less common and less well-defined genetic syndromes may increase the risk of ovarian cancer, but their contribution to genetic risk is small. A clear etiology for sporadic ovarian cancer has not been identified, but risk is affected by reproductive and hormonal factors. Surgery has a unique role in ovarian cancer, as it is used not only for diagnosis and staging but also therapeutically, even in patients with widely disseminated, advanced disease. Ovarian cancer is highly sensitive to chemotherapy drugs, particularly the platinum agents, and most patients will attain a remission with initial treatment. Recent advances in the delivery of chemotherapy using the intraperitoneal route have further improved survival after initial therapy. Although the majority of ovarian cancer patients will respond to initial chemotherapy, most will ultimately develop disease recurrence. Chemotherapy for recurrent disease includes platinum-based, multiagent regimens for women whose disease recurs more than 6 to 12 months after the completion of initial therapy and sequential single agents for those whose disease recurs earlier. New targeted biologic agents, particularly those involved with the vascular endothelial growth factor pathway and those targeting the poly (ADP-ribose) polymerase (PARP) enzyme, hold great promise for improving the outcome of ovarian cancer. PMID:21521830

Temporary ovarian suppression during chemotherapy to preserve ovarian function and fertility in breast cancer patients: A GRADE approach for evidence evaluation and recommendations by the Italian Association of Medical Oncology.

PubMed

Lambertini, Matteo; Cinquini, Michela; Moschetti, Ivan; Peccatori, Fedro A; Anserini, Paola; Valenzano Menada, Mario; Tomirotti, Maurizio; Del Mastro, Lucia

2017-01-01

The development of premature ovarian failure and subsequent infertility are possible consequences of chemotherapy use in pre-menopausal women with early-stage breast cancer. Among the available strategies for fertility preservation, pharmacological protection of the ovaries using luteinising hormone-releasing hormone analogues (LHRHa) during chemotherapy has the potential to restore ovarian function and fertility after anticancer treatments; however, the possible efficacy and clinical application of this strategy has been highly debated in the last years. Following the availability of new data on this controversial topic, the Panel of the Italian Association of Medical Oncology (AIOM) Clinical Practice Guideline on fertility preservation in cancer patients decided to apply the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) methodology around the relevant and current question on the clinical utility of temporary ovarian suppression with LHRHa during chemotherapy as a strategy to preserve ovarian function and fertility in breast cancer patients. To answer this question, preservation of ovarian function and fertility were judged as critical outcomes for the decision-making. Three possible outcomes of harm were identified: LHRHa-associated toxicities, potential antagonism between concurrent LHRHa and chemotherapy, and lack of the prognostic impact of chemotherapy-induced premature ovarian failure. According to the GRADE evaluation conducted, the result was a strong positive recommendation in favour of using this option to preserve ovarian function and fertility in breast cancer patients. The present manuscript aims to update and summarise the evidence for the use of this strategy in light of the new data published up to January 2016, according to the GRADE process. Copyright © 2016 Elsevier Ltd. All rights reserved.

The presence of an insulin-like androgenic gland factor (IAG) and insulin-like peptide binding protein (ILPBP) in the ovary of the blue crab, Callinectes sapidus and their roles in ovarian development.

PubMed

Huang, Xiaoshuai; Ye, Haihui; Chung, J Sook

2017-08-01

Insulin-like androgenic gland factor (IAG) that is produced by the male androgenic gland (AG), plays a role in sexual differentiation and maintenance of male secondary sex characteristics in decapod crustaceans. With an earlier finding of IAG expression in a female Callinectes sapidus ovary, we aimed to examine a putative role of IAG during the ovarian development of this species. To this end, the full-length cDNA sequence of the ovarian CasIAG (termed CasIAG-ova) has been isolated. The predicted mature peptide sequence of CasIAG-ova is identical to that of the IAG from the AG, except in their signal peptide regions. The CasIAG-ova contains an alternative initiation codon (UUG) as the start codon, which suggests that the translational regulation of CasIAG-ova may differ from that of the IAG from AG. To define the function of CasIAG-ova, the expressions of CasIAG-ova as well as its putative binding protein, insulin-like peptide binding protein (ILPBP), are measured in the ovaries at various developmental stages obtained from different seasons. Season affects both CasIAG and ILPBP expression in the ovary. Overall, summer females at earlier ovarian stages contain high levels of CasIAG and ILPBP than spring or fall females. These findings indicate that CasIAG-ova and CasILPBP may be involved in the ovarian development. When comparing the levels of CasIAG and CasILPBP in the ovary, the latter are much higher (∼10-10000 fold) than the former. Expression patterns of CasILPBP differ from those of CasIAG-ova during ovarian development and by season, suggesting that ILPBP may have an additional role in ovarian development rather than a function of a putative binding protein of IAG. Copyright © 2017 Elsevier Inc. All rights reserved.

The role of aromatase inhibitors in ameliorating deleterious effects of ovarian stimulation on outcome of infertility treatment

PubMed Central

Mitwally, Mohamed FM; Casper, Robert F; Diamond, Michael P

2005-01-01

Clinical utilization of ovulation stimulation to facilitate the ability of a couple to conceive has not only provided a valuable therapeutic approach, but has also yielded extensive information on the physiology of ovarian follicular recruitment, endometrial receptivity and early embryo competency. One of the consequences of the use of fertility enhancing agents for ovarian stimulation has been the creation of a hyperestrogenic state, which may influence each of these parameters. Use of aromatase inhibitors reduces hyperestrogenism inevitably attained during ovarian stimulation. In addition, the adjunct use of aromatase inhibitors during ovarian stimulation reduces amount of gonadotropins required for optimum stimulation. The unique approach of reducing hyperestrogenism, as well as lowering amount of gonadotropins without affecting the number of mature ovarian follicles is an exciting strategy that could result in improvement in the treatment outcome by ameliorating the deleterious effects of the ovarian stimulation on follicular development, endometrial receptivity, as well as oocyte and embryo quality. PMID:16202169

Peroxisome proliferator-activated receptors (PPARs) and ovarian function – implications for regulating steroidogenesis, differentiation, and tissue remodeling

PubMed Central

Komar, Carolyn M

2005-01-01

The peroxisome proliferator-activated receptors (PPARs) are a family of transcription factors involved in varied and diverse processes such as steroidogenesis, angiogenesis, tissue remodeling, cell cycle, apoptosis, and lipid metabolism. These processes are critical for normal ovarian function, and all three PPAR family members – alpha, delta, and gamma, are expressed in the ovary. Most notably, the expression of PPARgamma is limited primarily to granulosa cells in developing follicles, and is regulated by luteinizing hormone (LH). Although much has been learned about the PPARs since their initial discovery, very little is known regarding their function in ovarian tissue. This review highlights what is known about the roles of PPARs in ovarian cells, and discusses potential mechanisms by which PPARs could influence ovarian function. Because PPARs are activated by drugs currently in clinical use (fibrates and thiazolidinediones), it is important to understand their role in the ovary, and how manipulation of their activity may impact ovarian physiology as well as ovarian pathology. PMID:16131403

In utero exposure to low doses of environmental pollutants disrupts fetal ovarian development in sheep

PubMed Central

Fowler, Paul A.; Dorà, Natalie J.; McFerran, Helen; Amezaga, Maria R.; Miller, David W.; Lea, Richard G.; Cash, Phillip; McNeilly, Alan S.; Evans, Neil P.; Cotinot, Corinne; Sharpe, Richard M.; Rhind, Stewart M.

2008-01-01

Epidemiological studies of the impact of environmental chemicals on reproductive health demonstrate consequences of exposure but establishing causative links requires animal models using ‘real life’ in utero exposures. We aimed to determine whether prolonged, low-dose, exposure of pregnant sheep to a mixture of environmental chemicals affects fetal ovarian development. Exposure of treated ewes (n = 7) to pollutants was maximized by surface application of processed sewage sludge to pasture. Control ewes (n = 10) were reared on pasture treated with inorganic fertilizer. Ovaries and blood were collected from fetuses (n = 15 control and n = 8 treated) on Day 110 of gestation for investigation of fetal endocrinology, ovarian follicle/oocyte numbers and ovarian proteome. Treated fetuses were 14% lighter than controls but fetal ovary weights were unchanged. Prolactin (48% lower) was the only measured hormone significantly affected by treatment. Treatment reduced numbers of growth differentiation factor (GDF9) and induced myeloid leukaemia cell differentiation protein (MCL1) positive oocytes by 25–26% and increased pro-apoptotic BAX by 65% and 42% of protein spots in the treated ovarian proteome were differently expressed compared with controls. Nineteen spots were identified and included proteins involved in gene expression/transcription, protein synthesis, phosphorylation and receptor activity. Fetal exposure to environmental chemicals, via the mother, significantly perturbs fetal ovarian development. If such effects are replicated in humans, premature menopause could be an outcome. PMID:18436539

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

PubMed

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

2015-01-01

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

CPTAC Releases Cancer Proteome Confirmatory Ovarian Study Data | Office of Cancer Clinical Proteomics Research

Cancer.gov

A catalogue of molecular aberrations that cause ovarian cancer is critical for developing and deploying diagnostics and therapies that will improve patients’ lives. Because a comprehensive molecular view of cancer is important for ultimately guiding treatment, the National Cancer Institute (NCI) Clinical Proteomic Tumor Analysis Consortium (CPTAC) has released the cancer proteome confirmatory ovarian study data sets.

Hypothalamic-pituitary, ovarian and adrenal contributions to polycystic ovary syndrome.

PubMed

Baskind, N Ellissa; Balen, Adam H

2016-11-01

Polycystic ovary syndrome (PCOS) is a prevalent heterogeneous disorder linked with disturbances of reproductive, endocrine and metabolic function. The definition and aetiological hypotheses of PCOS are continually developing to incorporate evolving evidence of the syndrome, which appears to be both multifactorial and polygenic. The pathophysiology of PCOS encompasses inherent ovarian dysfunction that is strongly influenced by external factors including the hypothalamic-pituitary axis and hyperinsulinaemia. Neuroendocrine abnormalities including increased gonadotrophin-releasing hormone (GnRH) pulse frequency with consequent hypersecretion of luteinising hormone (LH) affects ovarian androgen synthesis, folliculogenesis and oocyte development. Disturbed ovarian-pituitary and hypothalamic feedback accentuates the gonadotrophin abnormalities, and there is emerging evidence putatively implicating dysfunction of the Kiss 1 system. Within the follicle subunit itself, there are intra-ovarian paracrine modulators, cytokines and growth factors, which appear to play a role. Adrenally derived androgens may also contribute to the pathogenesis of PCOS, but their role is less defined. Copyright © 2016. Published by Elsevier Ltd.

DNA methylation profiles of ovarian epithelial carcinoma tumors and cell lines.

PubMed

Houshdaran, Sahar; Hawley, Sarah; Palmer, Chana; Campan, Mihaela; Olsen, Mari N; Ventura, Aviva P; Knudsen, Beatrice S; Drescher, Charles W; Urban, Nicole D; Brown, Patrick O; Laird, Peter W

2010-02-22

Epithelial ovarian carcinoma is a significant cause of cancer mortality in women worldwide and in the United States. Epithelial ovarian cancer comprises several histological subtypes, each with distinct clinical and molecular characteristics. The natural history of this heterogeneous disease, including the cell types of origin, is poorly understood. This study applied recently developed methods for high-throughput DNA methylation profiling to characterize ovarian cancer cell lines and tumors, including representatives of three major histologies. We obtained DNA methylation profiles of 1,505 CpG sites (808 genes) in 27 primary epithelial ovarian tumors and 15 ovarian cancer cell lines. We found that the DNA methylation profiles of ovarian cancer cell lines were markedly different from those of primary ovarian tumors. Aggregate DNA methylation levels of the assayed CpG sites tended to be higher in ovarian cancer cell lines relative to ovarian tumors. Within the primary tumors, those of the same histological type were more alike in their methylation profiles than those of different subtypes. Supervised analyses identified 90 CpG sites (68 genes) that exhibited 'subtype-specific' DNA methylation patterns (FDR<1%) among the tumors. In ovarian cancer cell lines, we estimated that for at least 27% of analyzed autosomal CpG sites, increases in methylation were accompanied by decreases in transcription of the associated gene. The significant difference in DNA methylation profiles between ovarian cancer cell lines and tumors underscores the need to be cautious in using cell lines as tumor models for molecular studies of ovarian cancer and other cancers. Similarly, the distinct methylation profiles of the different histological types of ovarian tumors reinforces the need to treat the different histologies of ovarian cancer as different diseases, both clinically and in biomarker studies. These data provide a useful resource for future studies, including those of potential tumor progenitor cells, which may help illuminate the etiology and natural history of these cancers.

The role of biomarkers in the management of epithelial ovarian cancer.

PubMed

Yang, Wei-Lei; Lu, Zhen; Bast, Robert C

2017-06-01

Despite advances in surgery and chemotherapy for ovarian cancer, 70% of women still succumb to the disease. Biomarkers have contributed to the management of ovarian cancer by monitoring response to treatment, detecting recurrence, distinguishing benign from malignant pelvic masses and attempting to detect disease at an earlier stage. Areas covered: This review focuses on recent advances in biomarkers and imaging for management of ovarian cancer with particular emphasis on early detection. Relevant literature has been reviewed and analyzed. Expert commentary: Rising or persistent CA125 blood levels provide a highly specific biomarker for epithelial ovarian cancer, but not an optimally sensitive biomarker. Addition of HE4, CA 72.4, anti-TP53 autoantibodies and other biomarkers can increase sensitivity for detecting early stage or recurrent disease. Detecting disease recurrence will become more important as more effective therapy is developed. Early detection will require the development not only of biomarker panels, but also of more sensitive and specific imaging strategies. Effective biomarker strategies are already available for distinguishing benign from malignant pelvic masses, but their use in identifying and referring patients with probable ovarian cancer to gynecologic oncologists for cytoreductive operations must be encouraged.

Xenotransplantation in immunodeficient mice to study ovarian follicular development in domestic animals.

PubMed

Bols, P E J; Aerts, J M J; Langbeen, A; Goovaerts, I G F; Leroy, J L M R

2010-04-01

Nowadays, in vitro study of follicular dynamics of primordial and primary follicular stages is limited because in vitro culture systems for these follicles are lacking, both in domestic animal species and in human. Therefore, additional insights might be generated by grafting ovarian tissue into immunodeficient mice to study activation and maturation of early follicular stages. A considerable amount of data has already been gathered in laboratory animals and through clinical application of human assisted reproduction technologies where live births were reported recently after the use of (cryopreserved) ovarian grafts. However, given that human preantral follicles are difficult to obtain and that there are many similarities between the bovine and human species with regard to ovarian physiology, the bovine model offers exciting additional prospects and is therefore discussed in more detail. This review will focus on recent developments related to preantral follicle and (repeated) ovarian tissue retrieval and xenotransplantation of (bovine) ovarian tissue strips to immunodeficient mice as a model to study preantral follicular dynamics. Different grafting strategies will be discussed as well as the consequences of this procedure on the viability and dynamic behavior of the grafted tissue and follicles. 2010 Elsevier Inc. All rights reserved.

Concomitant endometriosis in malignant and borderline ovarian tumours.

PubMed

Oral, Engin; Aydin, Ovgu; Kumbak, Banu Aygun; İlvan, Sennur; Yilmaz, Handan; Tustas, Esra; Bese, Tugan; Demirkiran, Fuat; Arvas, Macit

2018-06-08

The aim of the study was to reveal the prevalence of concomitant endometriosis in malignant and borderline ovarian tumours. A retrospective analysis was performed of 530 patients with malignant ovarian tumours and 131 with borderline ovarian tumours, who underwent surgery in our hospital between 1995 and 2011. Forty-eight (7.3%) of 661 patients with malignant and borderline ovarian tumours were associated with endometriosis. Of the 48 endometriosis cases, 73% of those were atypical. Infertility was noted in 38% of patients with endometriosis-associated ovarian tumours. The most frequently endometriosis-associated subtypes were endometrioid (33%) and clear cell (18%) histologies. Of endometriosis-associated endometrioid and clear cell ovarian tumours, 70% were early stage and 60% were premenopausal. The prevalence of concomitant endometriosis in borderline tumours (12%) was found to be significantly higher than that found in the malignant ones (6%; p = .02). Of 32 endometriosis-associated malignant ovarian tumours, 69% were FIGO stages I and II. In conclusion, ovarian endometriosis is seen with both malignant and borderline ovarian tumours, the association being significant with borderline tumours. Fortunately, the endometriosis-associated malignant ovarian tumours are mostly early stage. Impact statement What is already known on this subject? Epidemiologic data suggest that endometriosis has malignant potential. However, a subgroup of women with endometriosis at a high risk for ovarian cancer is yet to be clarified. Currently, endometriosis and ovarian cancer association does not seem to have a clinical implication. What do the results of this study add? The findings of this study revealed that nearly 75% of endometriosis-associated ovarian tumours were of atypical endometriosis. Half of endometriosis-associated ovarian tumour cases were of endometrioid/clear cell histology and 70% were early-stage. Endometriosis was significantly associated with borderline ovarian tumours and the endometriosis-associated malignant ovarian tumours were mostly early stage. What are the implications of these findings for clinical practice and/or further research? Additional studies need to be conducted to develop screening approaches for malignant transformation or an association in women with endometriosis. Till that time, a change of current clinical practices cannot be justified. However, counselling and treating women with endometriosis who are at high risk for cancer coexistence or conversion is encouraged.

miR-132 targeting E2F5 suppresses cell proliferation, invasion, migration in ovarian cancer cells

PubMed Central

Tian, Hang; Hou, Lei; Xiong, Yu-Mei; Huang, Jun-Xiang; Zhang, Wen-Hua; Pan, Yong-Ying; Song, Xing-Rong

2016-01-01

Accumulating evidence showed that microRNA-132 (miR-132) are involved in development and progression of several types of cancers, however, the function and underlying molecular mechanism of miR-132 in ovarian cancer remains unclear. In this study we investigated the biological roles and molecular mechanism of miR-132 in ovarian cancer. Here, we found that that the expression levels of miR-132 were dramatically decreased in ovarian cancer cell lines and clinical ovarian cancer tissue samples. Then, we found that introduction of miR-132 significantly suppressed the proliferation, colony formation, migration and invasion of ovarian cancer cells. Mechanism investigation revealed that miR-132 inhibited the expression of transcription factor E2F5 by specifically targeting its mRNA 3’UTR. Moreover, the expression level of E2F5 was significantly increased in ovarian cancer tissues than in the adjacent normal tissues, and its expression was inversely correlated with miR-132 expression in clinical ovarian cancer tissues. Additionally, silencing E2F5 was able to inhibit the proliferation, colony formation, migration and invasion of ovarian cancer cells, parallel to the effect of miR-132 overexpression on the ovarian cancer cells. Meanwhile, overexpression of E2F5 reversed the inhibition effect mediated by miR-132 overexpression. These results indicate that miR-132 suppresses the cell proliferation, invasion, migration in ovarian cancer cells by targeting E2F5. PMID:27186275

miR-132 targeting E2F5 suppresses cell proliferation, invasion, migration in ovarian cancer cells.

PubMed

Tian, Hang; Hou, Lei; Xiong, Yu-Mei; Huang, Jun-Xiang; Zhang, Wen-Hua; Pan, Yong-Ying; Song, Xing-Rong

2016-01-01

Accumulating evidence showed that microRNA-132 (miR-132) are involved in development and progression of several types of cancers, however, the function and underlying molecular mechanism of miR-132 in ovarian cancer remains unclear. In this study we investigated the biological roles and molecular mechanism of miR-132 in ovarian cancer. Here, we found that that the expression levels of miR-132 were dramatically decreased in ovarian cancer cell lines and clinical ovarian cancer tissue samples. Then, we found that introduction of miR-132 significantly suppressed the proliferation, colony formation, migration and invasion of ovarian cancer cells. Mechanism investigation revealed that miR-132 inhibited the expression of transcription factor E2F5 by specifically targeting its mRNA 3'UTR. Moreover, the expression level of E2F5 was significantly increased in ovarian cancer tissues than in the adjacent normal tissues, and its expression was inversely correlated with miR-132 expression in clinical ovarian cancer tissues. Additionally, silencing E2F5 was able to inhibit the proliferation, colony formation, migration and invasion of ovarian cancer cells, parallel to the effect of miR-132 overexpression on the ovarian cancer cells. Meanwhile, overexpression of E2F5 reversed the inhibition effect mediated by miR-132 overexpression. These results indicate that miR-132 suppresses the cell proliferation, invasion, migration in ovarian cancer cells by targeting E2F5.

Ovarian mast cells migrate toward ovary-fimbria connection in neonatal MRL/MpJ mice.

PubMed

Nakamura, Teppei; Chihara, Masataka; Ichii, Osamu; Otsuka-Kanazawa, Saori; Nagasaki, Ken-Ichi; Elewa, Yaser Hosny Ali; Tatsumi, Osamu; Kon, Yasuhiro

2018-01-01

MRL/MpJ mice have abundant ovarian mast cells (MCs) as compared with other strains at postnatal day 0 (P0); however, they sharply decrease after birth. These ovarian MCs, particularly beneath the ovarian surface epithelium (SE), which express mucosal MC (MMC) marker, might participate in early follicular development. This study investigated the changes in spatiotemporal distribution of MCs in the perinatal MRL/MpJ mouse ovaries. At P0 to P7, the MCs were densely localized to the ovary, especially their caudomedial region around the ovary-fimbria connection. The neonatal ovarian MCs showed intermediate characteristics of MMC and connective tissue MC (CTMC), and the latter phenotype became evident with aging. However, the expression ratio of the MMC to CTMC marker increased from P0 to P4 in the MRL/MpJ mouse ovary. Similarly, the ratio of MCs facing SE to total MC number increased with aging, although the number of ovarian MCs decreased, indicating the relative increase in MMC phenotypes in the early neonatal ovary. Neither proliferating nor apoptotic MCs were found in the MRL/MpJ mouse ovaries. The parenchymal cells surrounding MCs at ovary-fimbria connection showed similar molecular expression patterns (E-cadherin+/Foxl2-/Gata4+) as that of the ovarian surface epithelial cells. At P2, around the ovary-fimbria connection, c-kit- immature oocytes formed clusters called nests, and some MCs localized adjacent to c-kit- oocytes within the nests. These results indicated that in postnatal MRL/MpJ mice, ovarian MCs changed their distribution by migrating toward the parenchymal cells composing ovary-fimbria connection, which possessed similar characteristics to the ovarian surface epithelium. Thus, we elucidated the spatiotemporal alterations of the ovarian MCs in MRL/MpJ mice, and suggested their importance during the early follicular development by migrating toward the ovary-fimbria connection. MRL/MpJ mice would be useful to elucidate the relationship between neonatal immunity and reproductive systems.

Ovarian mast cells migrate toward ovary-fimbria connection in neonatal MRL/MpJ mice

PubMed Central

Chihara, Masataka; Ichii, Osamu; Otsuka-Kanazawa, Saori; Nagasaki, Ken-ichi; Elewa, Yaser Hosny Ali; Tatsumi, Osamu; Kon, Yasuhiro

2018-01-01

MRL/MpJ mice have abundant ovarian mast cells (MCs) as compared with other strains at postnatal day 0 (P0); however, they sharply decrease after birth. These ovarian MCs, particularly beneath the ovarian surface epithelium (SE), which express mucosal MC (MMC) marker, might participate in early follicular development. This study investigated the changes in spatiotemporal distribution of MCs in the perinatal MRL/MpJ mouse ovaries. At P0 to P7, the MCs were densely localized to the ovary, especially their caudomedial region around the ovary-fimbria connection. The neonatal ovarian MCs showed intermediate characteristics of MMC and connective tissue MC (CTMC), and the latter phenotype became evident with aging. However, the expression ratio of the MMC to CTMC marker increased from P0 to P4 in the MRL/MpJ mouse ovary. Similarly, the ratio of MCs facing SE to total MC number increased with aging, although the number of ovarian MCs decreased, indicating the relative increase in MMC phenotypes in the early neonatal ovary. Neither proliferating nor apoptotic MCs were found in the MRL/MpJ mouse ovaries. The parenchymal cells surrounding MCs at ovary-fimbria connection showed similar molecular expression patterns (E-cadherin+/Foxl2-/Gata4+) as that of the ovarian surface epithelial cells. At P2, around the ovary-fimbria connection, c-kit- immature oocytes formed clusters called nests, and some MCs localized adjacent to c-kit- oocytes within the nests. These results indicated that in postnatal MRL/MpJ mice, ovarian MCs changed their distribution by migrating toward the parenchymal cells composing ovary-fimbria connection, which possessed similar characteristics to the ovarian surface epithelium. Thus, we elucidated the spatiotemporal alterations of the ovarian MCs in MRL/MpJ mice, and suggested their importance during the early follicular development by migrating toward the ovary-fimbria connection. MRL/MpJ mice would be useful to elucidate the relationship between neonatal immunity and reproductive systems. PMID:29684078

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

PubMed

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

2017-10-01

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

The Increased Expression of Connexin and VEGF in Mouse Ovarian Tissue Vitrification by Follicle Stimulating Hormone

PubMed Central

Yang, Yanzhou; Chen, Jie; Wu, Hao; Pei, Xiuying; Chang, Qing; Ma, Wenzhi; Ma, Huiming; Hei, Changchun; Zheng, Xiaomin; Cai, Yufang; Zhao, Chengjun; Yu, Jia; Wang, Yanrong

2015-01-01

Ovarian follicular damages were caused by cryoinjury during the process of ovarian vitrification and ischemia/reperfusion during the process of ovarian transplantation. And appropriate FSH plays an important role in antiapoptosis during ovarian follicle development. Therefore, in this study, 0.3 IU/mL FSH was administered into medium during mouse ovarian cryopreservation by vitrification to ascertain the function of FSH on ovarian vitrification and avascular transplantation. The results suggested that the expressions of Cx37, Cx43, apoptotic molecular caspase-3, and angiogenesis molecular VEGF were confirmed using immunohistochemistry, western blotting, and real-time PCR, and the results suggested that the treatment with FSH remarkably increased the number of morphologically normal follicles in vitrified/warmed ovaries by upregulating the expression of Cx37, Cx43, VEGF, and VEGF receptor 2, but downregulating the expression of caspase-3. In addition, the vitrified/warmed ovaries were transplanted, and the related fertility was analyzed, and the results suggested that the fertility, neoangiogenesis, and follicle reserve were remarkably increased in the FSH administrated group. Taken together, administration of 0.3 IU/mL FSH during ovarian cryopreservation by vitrification can maintain ovarian survival during ovarian vitrification and increases the blood supply with avascular transplantation via upregulation of Cx43, Cx37, and VEGF/VEGFR2, as well as through its antiapoptotic effects. PMID:26539488

Overexpression of Notch3 and pS6 Is Associated with Poor Prognosis in Human Ovarian Epithelial Cancer.

PubMed

Liu, Zhaoxia; Yun, Rongna; Yu, Xiaolin; Hu, Hui; Huang, Genhua; Tan, Buzhen; Chen, Tingtao

2016-01-01

Notch3 and pS6 play important roles in tumor angiogenesis. To assess the expression of Notch3 and pS6 in Chinese ovarian epithelial cancer patients, a ten-year follow-up study was performed in ovarian epithelial cancer tissues from 120 specimens of human ovarian epithelial cancer, 30 specimens from benign ovarian tumors, and 30 samples from healthy ovaries by immunohistochemistry. The results indicate that the expression of Notch3 and pS6 was higher in ovarian epithelial cancer than in normal ovary tissues and in benign ovarian tumor tissues (p < 0.01). In tumor tissues, Notch3 expression and pS6 expression were negatively associated with age (p > 0.05) but positively associated with clinical stage, pathological grading, histologic type, lymph node metastasis, and ascites (p < 0.05 or p < 0.01). A follow-up survey of 64 patients with ovarian epithelial cancer showed that patients with high Notch3 and pS6 expression had a shorter survival time (p < 0.01), in which the clinical stage (p < 0.05) and Notch3 expression (p < 0.01) played important roles. In conclusion, Notch3 and pS6 are significantly related to ovarian epithelial cancer development and prognosis, and their combination represents a potential biomarker and therapeutic target in ovarian tumor angiogenesis.

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

PubMed

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

2008-08-01

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

Ovarian Cysts

MedlinePlus

... mature in the ovaries, are released in monthly cycles during the childbearing years. Many women have ovarian ... cysts develop as a result of your menstrual cycle (functional cysts). Other types of cysts are much ...

Disordered follicle development

PubMed Central

Chang, R. Jeffrey; Cook-Andersen, Heidi

2013-01-01

Alterations of ovarian follicle morphology and function have been well documented in women with PCOS. These include increased numbers of growing preantral follicles, failure of follicle growth beyond the mid-antral stage, evidence of granulosa call degeneration, and theca cell hyperplasia. Functional abnormalities include paradoxical granulosa cell hyperresponsiveness to FSH which is clinically linked to ovarian hyperstimulation during ovulation induction. In addition, there is likely a primary theca cell defect that accounts for the majority of excess androgen production in this disorder. The precise mechanisms responsible for altered follicle function are not completely clear. However, several factors appear to influence normal advancement of follicle development as well as impair ovarian steroidogenesis. These include intra- as well as extraovarian influences that distort normal ovarian growth and disrupt steroid production by follicle cells. PMID:22874072

Therapeutic targets and new directions for antibodies developed for ovarian cancer

PubMed Central

Bax, Heather J.; Josephs, Debra H.; Pellizzari, Giulia; Spicer, James F.; Montes, Ana; Karagiannis, Sophia N.

2016-01-01

ABSTRACT Antibody therapeutics against different target antigens are widely used in the treatment of different malignancies including ovarian carcinomas, but this disease still requires more effective agents. Improved understanding of the biological features, signaling pathways, and immunological escape mechanisms involved in ovarian cancer has emerged in the past few years. These advances, including an appreciation of the cross-talk between cancer cells and the patient's immune system, have led to the identification of new targets. In turn, potential antibody treatments with various mechanisms of action, including immune activation or toxin-delivery, that are directed at these targets have been developed. Here, we identify established as well as novel targets for antibodies in ovarian cancer, and discuss how they may provide fresh opportunities to identify interventions with enhanced therapeutic potential. PMID:27494775

Ovarian Cancer Differential Interactome and Network Entropy Analysis Reveal New Candidate Biomarkers.

PubMed

Ayyildiz, Dilara; Gov, Esra; Sinha, Raghu; Arga, Kazim Yalcin

2017-05-01

Ovarian cancer is one of the most common cancers and has a high mortality rate due to insidious symptoms and lack of robust diagnostics. A hitherto understudied concept in cancer pathogenesis may offer new avenues for innovation in ovarian cancer biomarker development. Cancer cells are characterized by an increase in network entropy, and several studies have exploited this concept to identify disease-associated gene and protein modules. We report in this study the changes in protein-protein interactions (PPIs) in ovarian cancer within a differential network (interactome) analysis framework utilizing the entropy concept and gene expression data. A compendium of six transcriptome datasets that included 140 samples from laser microdissected epithelial cells of ovarian cancer patients and 51 samples from healthy population was obtained from Gene Expression Omnibus, and the high confidence human protein interactome (31,465 interactions among 10,681 proteins) was used. The uncertainties of the up- or downregulation of PPIs in ovarian cancer were estimated through an entropy formulation utilizing combined expression levels of genes, and the interacting protein pairs with minimum uncertainty were identified. We identified 105 proteins with differential PPI patterns scattered in 11 modules, each indicating significantly affected biological pathways in ovarian cancer such as DNA repair, cell proliferation-related mechanisms, nucleoplasmic translocation of estrogen receptor, extracellular matrix degradation, and inflammation response. In conclusion, we suggest several PPIs as biomarker candidates for ovarian cancer and discuss their future biological implications as potential molecular targets for pharmaceutical development as well. In addition, network entropy analysis is a concept that deserves greater research attention for diagnostic innovation in oncology and tumor pathogenesis.

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

Optical Biomarkers of Serous and Mucinous Human Ovarian Tumor Assessed with Nonlinear Optics Microscopies

PubMed Central

Adur, Javier; Pelegati, Vitor B.; de Thomaz, Andre A.; Baratti, Mariana O.; Almeida, Diogo B.; Andrade, L. A. L. A.; Bottcher-Luiz, Fátima; Carvalho, Hernandes F.; Cesar, Carlos L.

2012-01-01

Background Nonlinear optical (NLO) microscopy techniques have potential to improve the early detection of epithelial ovarian cancer. In this study we showed that multimodal NLO microscopies, including two-photon excitation fluorescence (TPEF), second-harmonic generation (SHG), third-harmonic generation (THG) and fluorescence lifetime imaging microscopy (FLIM) can detect morphological and metabolic changes associated with ovarian cancer progression. Methodology/Principal Findings We obtained strong TPEF + SHG + THG signals from fixed samples stained with Hematoxylin & Eosin (H&E) and robust FLIM signal from fixed unstained samples. Particularly, we imaged 34 ovarian biopsies from different patients (median age, 49 years) including 5 normal ovarian tissue, 18 serous tumors and 11 mucinous tumors with the multimodal NLO platform developed in our laboratory. We have been able to distinguish adenomas, borderline, and adenocarcinomas specimens. Using a complete set of scoring methods we found significant differences in the content, distribution and organization of collagen fibrils in the stroma as well as in the morphology and fluorescence lifetime from epithelial ovarian cells. Conclusions/Significance NLO microscopes provide complementary information about tissue microstructure, showing distinctive patterns for serous and mucinous ovarian tumors. The results provide a basis to interpret future NLO images of ovarian tissue and lay the foundation for future in vivo optical evaluation of premature ovarian lesions. PMID:23056557

JNK-1 Inhibition Leads to Antitumor Activity in Ovarian Cancer

PubMed Central

Vivas-Mejia, Pablo; Benito, Juliana Maria; Fernandez, Ariel; Han, Hee-Dong; Mangala, Lingegowda; Rodriguez-Aguayo, Cristian; Chavez-Reyes, Arturo; Lin, Yvonne G.; Nick, Alpa M.; Stone, Rebecca L.; Kim, Hye Sun; Claret, Francois-Xavier; Bornmann, William; Hennessy, Bryan TJ.; Sanguino, Angela; Peng, Zhengong; Sood, Anil K.; Lopez-Berestein, Gabriel

2011-01-01

Purpose To demonstrate the functional, clinical and biological significance of JNK-1 in ovarian carcinoma. Experimental Design Analysis of the impact of JNK on 116 epithelial ovarian cancers was conducted. The role of JNK in vitro and in experimental models of ovarian cancer was assessed. We studied the role of WBZ_4, a novel JNK inhibitor redesigned from imatinib based on targeting wrapping defects, in cell lines and in experimental models of ovarian cancer. Results We found a significant association of pJNK with progression free survival in the 116 epithelial ovarian cancers obtained at primary debulking therapy. WBZ_4 led to cell growth inhibition and increased apoptosis in a dose dependent fashion in four ovarian cancer cell lines. In vivo, while imatinib had no effect on tumor growth, WBZ_4 inhibited tumor growth in orthotopic murine models of ovarian cancer. The anti-tumor effect was further increased in combination with docetaxel. Silencing of JNK-1 with systemically administered siRNA led to significantly reduced tumor weights as compared to non-silencing siRNA controls, indicating that indeed the antitumor effects observed were due to JNK-1 inhibition. Conclusions These studies identify JNK-1 as an attractive therapeutic target in ovarian carcinoma and that the re-designed WBZ_4 compound should be considered for further clinical development. PMID:20028751

Litter size influences lamb weight and ovarian reserve but not reproductive tract development or expression of genes involved in early follicular development

USDA-ARS?s Scientific Manuscript database

In ruminants, development of the female reproductive tract starts before birth, and primordial follicles in the ovaries activate during the third trimester of gestation. Lambs born as twins have lower birth weights and smaller ovarian reserves than lambs born as singletons. We hypothesized that ew...

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

PubMed

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

2014-01-01

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

Recent Technological Advances in Using Mouse Models to Study Ovarian Cancer

PubMed Central

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

2014-01-01

Serous epithelial ovarian cancer (SEOC) is the most lethal gynecological cancer in the United States with disease recurrence being the major cause of morbidity and mortality. Despite recent advances in our understanding of the molecular mechanisms responsible for the development of SEOC, the survival rate for women with this disease has remained relatively unchanged in the last two decades. Preclinical mouse models of ovarian cancer, including xenograft, syngeneic, and genetically engineered mice, have been developed to provide a mechanism for studying the development and progression of SEOC. Such models strive to increase our understanding of the etiology and dissemination of ovarian cancer in order to overcome barriers to early detection and resistance to standard chemotherapy. Although there is not a single model that is most suitable for studying ovarian cancer, improvements have led to current models that more closely mimic human disease in their genotype and phenotype. Other advances in the field, such as live animal imaging techniques, allow effective monitoring of the microenvironment and therapeutic efficacy. New and improved preclinical mouse models, combined with technological advances to study such models, will undoubtedly render success of future human clinical trials for patients with SEOC. PMID:24592355

Ovarian cancer: prevention, detection, and treatment of the disease and its recurrence. Molecular mechanisms and personalized medicine meeting report.

PubMed

Modugno, Francesmary; Edwards, Robert P

2012-10-01

To review the current understanding of the underlying molecular, biologic, and genetic mechanisms involved in ovarian cancer development and how these mechanisms can be targets for prevention, detection, and treatment of the disease and its recurrence. In May 2012, we convened a meeting of researchers, clinicians, and consumer advocates to review the state of current knowledge on molecular mechanisms and identify fruitful areas for further investigations. The meeting consisted of 7 scientific sessions ranging from Epidemiology, Early Detection, and Biology to Therapeutics and Quality of Life. Sessions consisted of talks and panel discussions by international leaders in ovarian cancer research. A special career development session by the Congressionally Directed Medical Research Program Department of Defense Ovarian Cancer Academy as well as an oral abstract and poster session showcased promising new research by junior scientists. Technological advances in the last decade have increased our knowledge of the molecular mechanisms involved in a host of biological activities related to ovarian cancer. Understanding the role these mechanisms play in cancer initiation and progression will help lead to the development of prevention and treatment modalities that can be personalized to each patient, thereby helping to overcome this highly fatal malignancy.

Bioaccumulation Potential of Contaminants from Bedded and Suspended Oakland Harbor Deepening Project Sediments to San Francisco Bay Flatfish and Bivalve Mollusks

DTIC Science & Technology

1994-08-01

Descriptive Statistics of Sediment Conventional Parameters and Statistical Comparisons of Oil and Grease and Total Petroleum Hydrocarbon Concentrations in...7000 Series, USEPA 1986, Bloom and Crecelius 1987). Oil and grease, total petroleum hydrocarbons . BPNL. Oil and grease were determined accord- ing to...infrared spectrometer. Total petroleum hydrocarbons were determined according to Method 418.1 (USEPA 1983). Sediment samples were extracted with freon

Oncolytic virotherapy for ovarian cancer

PubMed Central

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

2012-01-01

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

HORMONAL CONTROL OF OVARIAN FUNCTION FOLLOWING CHLOROTRIAZINE EXPOSURE: EFFECT ON REPRODUCTIVE FUNCTION AND MAMMARY GLAND TUMOR DEVELOPMENT

EPA Science Inventory

Hormonal Control of Ovarian Function Following Chlorotriazine Exposure: Effect on Reproductive Function and Mammary Gland Tumor Development.

Ralph L. Cooper, Susan C. Laws, Michael G. Narotsky, Jerome M. Goldman, and Tammy E. Stoker

Abstract
The studies review...

Flutamide and biomarkers in women at high risk for ovarian cancer: preclinical and clinical evidence.

PubMed

Gruessner, Christine; Gruessner, Angelika; Glaser, Katherine; AbuShahin, Nisreen; Zhou, Yi; Laughren, Cynthia; Wright, Heather; Pinkerton, Samantha; Yi, Xiaofang; Stoffer, Jha'nae; Azodi, Masoud; Zheng, Wenxin; Chambers, Setsuko K

2014-09-01

We hypothesized that (i) preclinical biologic evidence exists for the role of androgens in ovarian cancer development and (ii) flutamide treatment of women at high risk for ovarian cancer may identify meaningful tissue biomarkers of androgen action and of ovarian cancer initiation. We showed that androgen ablation of male mice led to a 24-fold decrease in tumor burden from serous ovarian cells. In a phase II study, we studied the effect of preoperative flutamide treatment (125 mg/day × 6 weeks) in 12 women versus 47 controls, 47% with BRCA mutation. We analyzed immunohistochemical scores of candidate proteins CSF-1, CSF-1R, and ErbB4 in the epithelium and stroma of fallopian tube, ovary, and ovarian endosalpingiosis. Flutamide decreased the levels, notably, of CSF-1 and ErbB4 in ovarian stroma (P ≤ 0.0006) and ovarian endosalpingiosis (P ≤ 0.01), ErbB4 in ovarian epithelium (P = 0.006), and CSF-1R in ovarian endosalpingiosis (P = 0.009). Our logistic regression model clearly distinguished the flutamide patients from controls (P ≤ 0.0001). Our analysis of the precision of this model of CSF-1 and ErbB4 expression in ovarian stroma achieved 100% sensitivity and 97% specificity (AUC = 0.99). Thus, our data suggest that a short 6-week exposure of flutamide reversed elevated levels of CSF-1 and ErbB4 (both of which we had previously found correlated with high risk status). CSF-1 and ErbB4 in ovarian stroma led to a model with high predictive value for flutamide sensitivity. The effect of flutamide on marker expression in ovarian endosalpingiosis, previously associated with BRCA carrier status, suggests that ovarian endosalpingiosis may be a latent precursor to pelvic serous cancers. ©2014 American Association for Cancer Research.

Combination of plant and insect eggs as food sources facilitates ovarian development in an omnivorous bug Apolygus lucorum (Hemiptera: Miridae).

PubMed

Yuan, Wei; Li, Wenjing; Li, Yunhe; Wu, Kongming G

2013-06-01

Diet nutrient is considered as an important regulatory factor for reproduction of insects. To understand the effect of different food sources on the reproductive physiology of Apolygus lucorum (Meyer-Dür), the ovarian development in adult females was investigated when they were fed on green beans (Gb), combination of green beans Phaseolus vulgaris L and Helicoverpa armigera eggs (GbHe), or H. armigera eggs (He). A female of A. lucorum has two ovaries, and each ovary contained seven yellowish ovarioles. Females fed on Gb or GbHe had larger ovaries and the ovarioles contained larger numbers of oocytes compared with those fed on He. Females in GeHe treatment has significantly higher number of follicles per ovary throughout the whole adult period compared with those in Gb or He treatment. Furthermore, the length of the best developed ovariole was affected by the diet type. The females fed on GbHe had the most developed ovarioles, with significantly longer ovarioles than those fed on Gb or He. A method was described to quantitatively score the degree of ovarian development in the current study. Similarly, the ovarian development scores were significantly higher for females in GbHe treatment than those in other two diet treatments. The ovarian development significantly delayed for females fed on He. Our results demonstrate that A. lucorum, as an omnivorous insect species, can acquire nutrients from both plant and animal origin food sources, and the combination of plants and animal food sources can significantly facilitate the ovary development of its females.

Polycystic ovarian morphology in normal women does not predict the development of polycystic ovary syndrome.

PubMed

Murphy, M K; Hall, J E; Adams, J M; Lee, H; Welt, C K

2006-10-01

Polycystic ovarian morphology (PCOM) is present in 25% of normal women in the absence of polycystic ovary syndrome (PCOS); however, the natural history of PCOM is unknown. We hypothesized that the presence of PCOM predisposes the development of PCOS. The study was a longitudinal follow-up study over 8.2 +/- 5.2 yr (mean +/- sd; range 1.7-17.5 yr). The study took place in an outpatient setting. Women who took part in a previous study as a normal control and had an ultrasound examination (n = 40) participated. Subjects underwent an interval menstrual history, physical exam, blood sampling, and repeat ultrasound in the follicular phase. Development of PCOS was diagnosed by irregular menses and hyperandrogenism, in the absence of other disorders. Changes in ovarian morphology over time were evaluated. At the baseline visit, 23 women (57.5%) had PCOM and 17 (42.5%) had normal ovarian morphology. One subject with PCOM developed irregular menses and presumptive PCOS. Eleven subjects with PCOM no longer met the criteria for PCOM at follow-up. There was no factor that predicted the change to normal ovarian morphology at the follow-up visit. These data suggest that PCOM in women with regular ovulatory cycles does not commonly predispose the development of PCOS. Although it is unusual to develop PCOM if the ovaries are normal on first assessment, ovaries in women with PCOM no longer meet the criteria for PCOM in approximately half of cases over time.

Irregular menses predicts ovarian cancer: Prospective evidence from the Child Health and Development Studies.

PubMed

Cirillo, Piera M; Wang, Erica T; Cedars, Marcelle I; Chen, Lee-May; Cohn, Barbara A

2016-09-01

We tested the hypothesis that irregular menstruation predicts lower risk for ovarian cancer, possibly due to less frequent ovulation. We conducted a 50-year prospective study of 15,528 mothers in the Child Health and Development Studies cohort recruited from the Kaiser Foundation Health Plan from 1959 to 1966. Irregular menstruation was classified via medical record and self-report at age 26. We identified 116 cases and 84 deaths due to ovarian cancer through 2011 via linkage to the California Cancer Registry and Vital Statistics. Contrary to expectation, women with irregular menstrual cycles had a higher risk of ovarian cancer incidence and mortality over the 50-year follow-up. Associations increased with age (p <0.05). We observed a 2-fold increased incidence and mortality by age 70 (95% confidence interval [CI] = 1.1, 3.4) rising to a 3-fold increase by age 77 (95% CI = 1.5, 6.7 for incidence; 95% CI = 1.4, 5.9 for mortality). We also found a 3-fold higher risk of mortality for high-grade serous tumors (95% CI = 1.3, 7.6) that did not vary by age. This is the first prospective study to show an association between irregular menstruation and ovarian cancer-we unexpectedly found higher risk for women with irregular cycles. These women are easy to identify and many may have polycystic ovarian syndrome. Classifying high-risk phenotypes such as irregular menstruation creates opportunities to find novel early biomarkers, refine clinical screening protocols and potentially develop new risk reduction strategies. These efforts can lead to earlier detection and better survival for ovarian cancer. © 2016 UICC.

Regulation of fibrillins and modulators of TGFβ in fetal bovine and human ovaries.

PubMed

Bastian, Nicole A; Bayne, Rosemary A; Hummitzsch, Katja; Hatzirodos, Nicholas; Bonner, Wendy M; Hartanti, Monica D; Irving-Rodgers, Helen F; Anderson, Richard A; Rodgers, Raymond J

2016-08-01

Fibrillins 1-3 are stromal extracellular matrix proteins that play important roles in regulating TGFβ activity, which stimulates fibroblasts to proliferate and synthesize collagen. In the developing ovary, the action of stroma is initially necessary for the formation of ovigerous cords and subsequently for the formation of follicles and the surface epithelium of the ovary. FBN3 is highly expressed only in early ovarian development and then it declines. In contrast, FBN1 and 2 are upregulated in later ovarian development. We examined the expression of FBN1-3 in bovine and human fetal ovaries. We used cell dispersion and monolayer culture, cell passaging and tissue culture. Cells were treated with growth factors, hormones or inhibitors to assess the regulation of expression of FBN1-3 When bovine fetal ovarian tissue was cultured, FBN3 expression declined significantly. Treatment with TGFβ-1 increased FBN1 and FBN2 expression in bovine fibroblasts, but did not affect FBN3 expression. Additionally, in cultures of human fetal ovarian fibroblasts (9-17weeks gestational age), the expression of FBN1 and FBN2 increased with passage, whereas FBN3 dramatically decreased. Treatment with activin A and a TGFβ family signaling inhibitor, SB431542, differentially regulated the expression of a range of modulators of TGFβ signaling and of other growth factors in cultured human fetal ovarian fibroblasts suggesting that TGFβ signaling is differentially involved in the regulation of ovarian fibroblasts. Additionally, since the changes in FBN1-3 expression that occur in vitro are those that occur with increasing gestational age in vivo, we suggest that the fetal ovarian fibroblasts mature in vitro. © 2016 Society for Reproduction and Fertility.

MUS81 is associated with cell proliferation and cisplatin sensitivity in serous ovarian cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xie, Suhong; Zheng, Hui; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai

The dysfunction of DNA damage repair (DDR) pathway contributes to tumorigenesis and drug-resistance in cancer. MUS81 is a member of the conserved xeroderma pigmentosum group F (XPF) family protein of endonucleases, which is important to the DDR pathway. However, the role of MUS81 in the development of ovarian cancer remains uncertain. To explore the expression of MUS81 and its association to serous ovarian cancer (SOC), 43 biopsies of SOC patients were detected by qRT-PCR, and 29 specimens were further performed by immunohistochemistry analysis. Here, we observed that MUS81 was over-expressed in SOC tissues at both transcript and protein levels, andmore » the expression level of MUS81 protein in ovarian cancer cell lines was also higher than that in human normal ovarian surface epithelial cell line (HOSEpiC). We also found that down-regulation of MUS81 expression in ovarian cancer cells inhibited cell proliferation and colony formation ability, and influenced cell cycle progression. Moreover, inhibition of MUS81 expression induced cellular senescence and enhanced the antitumor effect of cisplatin. Down-regulation of MUS81 expression could suppress the growth and development of SOC. These results indicate that MUS81 might play important roles in the progression of SOC and influence the antitumor effect of cisplatin. - Highlights: • MUS81 was overexpression in serous ovarian cancer (SOC). • Meanwhile down-regulation of inhibited cell proliferation and influenced cell cycle progression. • Inhibition of MUS81 induced cell cellular senescence and enhanced the antitumor effect of cisplatin. • Down-regulation of MUS81 expression could suppress the growth and development of SOC.« less

Glutamate Cysteine Ligase Modifier Subunit (Gclm) Null Mice Have Increased Ovarian Oxidative Stress and Accelerated Age-Related Ovarian Failure

PubMed Central

Lim, Jinhwan; Nakamura, Brooke N.; Mohar, Isaac; Kavanagh, Terrance J.

2015-01-01

Glutathione (GSH) is the one of the most abundant intracellular antioxidants. Mice lacking the modifier subunit of glutamate cysteine ligase (Gclm), the rate-limiting enzyme in GSH synthesis, have decreased GSH. Our prior work showed that GSH plays antiapoptotic roles in ovarian follicles. We hypothesized that Gclm−/− mice have accelerated ovarian aging due to ovarian oxidative stress. We found significantly decreased ovarian GSH concentrations and oxidized GSH/oxidized glutathione redox potential in Gclm−/− vs Gclm+/+ ovaries. Prepubertal Gclm−/− and Gclm+/+ mice had similar numbers of ovarian follicles, and as expected, the total number of ovarian follicles declined with age in both genotypes. However, the rate of decline in follicles was significantly more rapid in Gclm−/− mice, and this was driven by accelerated declines in primordial follicles, which constitute the ovarian reserve. We found significantly increased 4-hydroxynonenal immunostaining (oxidative lipid damage marker) and significantly increased nitrotyrosine immunostaining (oxidative protein damage marker) in prepubertal and adult Gclm−/− ovaries compared with controls. The percentage of small ovarian follicles with increased granulosa cell proliferation was significantly higher in prepubertal and 2-month-old Gclm−/− vs Gclm+/+ ovaries, indicating accelerated recruitment of primordial follicles into the growing pool. The percentages of growing follicles with apoptotic granulosa cells were increased in young adult ovaries. Our results demonstrate increased ovarian oxidative stress and oxidative damage in young Gclm−/− mice, associated with an accelerated decline in ovarian follicles that appears to be mediated by increased recruitment of follicles into the growing pool, followed by apoptosis at later stages of follicular development. PMID:26083875

Keratin 5 overexpression is associated with serous ovarian cancer recurrence and chemotherapy resistance.

PubMed

Ricciardelli, Carmela; Lokman, Noor A; Pyragius, Carmen E; Ween, Miranda P; Macpherson, Anne M; Ruszkiewicz, Andrew; Hoffmann, Peter; Oehler, Martin K

2017-03-14

This study investigated the clinical significance of keratin 5 and 6 expression in serous ovarian cancer progression and chemotherapy resistance. KRT5 and KRT6 (KRT6A, KRT6B & KRT6C) gene expression was assessed in publically available serous ovarian cancer data sets, ovarian cancer cell lines and primary serous ovarian cancer cells. Monoclonal antibodies which detect both K5/6 or only K5 were used to assess protein expression in ovarian cancer cell lines and a cohort of high grade serous ovarian carcinomas at surgery (n = 117) and after neoadjuvant chemotherapy (n = 21). Survival analyses showed that high KRT5 mRNA in stage III/IV serous ovarian cancers was significantly associated with reduced progression-free (HR 1.38, P < 0.0001) and overall survival (HR 1.28, P = 0.013) whilst high KRT6 mRNA was only associated with reduced progression-free survival (HR 1.2, P = 0.031). Both high K5/6 (≥ 10%, HR 1.78 95% CI; 1.03-2.65, P = 0.017) and high K5 (≥ 10%, HR 1.90, 95% CI; 1.12-3.19, P = 0.017) were associated with an increased risk of disease recurrence. KRT5 but not KRT6C mRNA expression was increased in chemotherapy resistant primary serous ovarian cancer cells compared to chemotherapy sensitive cells. The proportion of serous ovarian carcinomas with high K5/6 or high K5 immunostaining was significantly increased following neoadjuvant chemotherapy. K5 can be used to predict serous ovarian cancer prognosis and identify cancer cells that are resistant to chemotherapy. Developing strategies to target K5 may therefore improve serous ovarian cancer survival.

Origins and health consequences of stress-induced ovarian dysfunction.

PubMed

Kaplan, Jay R

2008-01-01

Normal ovarian function is thought to protect women against coronary heart disease (CHD) and osteoporosis by delaying the pathobiological processes underlying these conditions. Supporting this proposition is the observation that, following menopause (i.e. the loss of cyclic ovarian function), these diseases accelerate and ultimately comprise a major portion of the health burden of older women. However, while all women eventually go through complete ovarian failure at menopause, many also experience episodes of cyclic ovarian disruption during their reproductive years (i.e. ages 18-40). These disruptions are relatively common and often are attributed to psychogenic factors (stress, anxiety, depression, or other emotional disturbance). This article hypothesizes that, to the extent that cyclic ovarian function affords protection against CHD and osteoporosis, ovulatory abnormalities associated with estrogen deficiency in young women - even if mild and subclinical - prematurely accelerate development of these two diseases of 'aging'. Consistent with this hypothesis are observations in group-housed, premenopausal monkeys confirming that reproductive deficits are commonly induced by psychosocial stress (social subordination), and, in the presence of a typical Western diet, accelerate the development of CHD and bone loss. Furthermore, in this model premenopausal disease extent predicts postmenopausal health outcomes irrespective of postmenopausal treatment, emphasizing the pathobiological importance of the premenopausal portion of the life cycle. Finally, data from both women and nonhuman primates suggest that reproductive deficits of the sort described here are adaptive when triggered appropriately, but detrimental when activated in an environment (e.g. sedentary lifestyle, high-fat diet) permissive to the development of chronic disease.

Ovarian Cancer Stroma: Pathophysiology and the Roles in Cancer Development

PubMed Central

Furuya, Mitsuko

2012-01-01

Ovarian cancer represents one of the cancers with the worst prognostic in adult women. More than half of the patients who present with clinical signs such as abdominal bloating and a feeling of fullness already show advanced stages. The majority of ovarian cancers grow as cystic masses, and cancer cells easily spread into the pelvic cavity once the cysts rupture or leak. When the ovarian cancer cells disseminate into the peritoneal cavity, metastatic nests may grow in the cul-de-sac, and in more advanced stages, the peritoneal surfaces of the upper abdomen become the next largest soil for cancer progression. Ascites is also produced frequently in ovarian cancers, which facilitates distant metastasis. Clinicopathologic, epidemiologic and molecular studies on ovarian cancers have improved our understanding and therapeutic approaches, but still further efforts are required to reduce the risks in the patients who are predisposed to this lethal disease and the mortality of the patients in advanced stages. Among various molecules involved in ovarian carcinogenesis, special genes such as TP53, BRCA1 and BRCA2 have been well investigated. These genes are widely accepted as the predisposing factors that trigger malignant transformation of the epithelial cells of the ovary. In addition, adnexal inflammatory conditions such as chronic salpingitis and ovarian endometriosis have been great research interests in the context of carcinogenic background of ovarian cancers. In this review, I discuss the roles of stromal cells and inflammatory factors in the carcinogenesis and progression of ovarian cancers. PMID:24213462

Spectropolarimetry in the differential diagnosis of benign and malignant ovarian tumors

NASA Astrophysics Data System (ADS)

Peresunko, O. P.; Yermolenko, S. B.; Gruia, I.

2018-01-01

The aim of this study was to use the spectrophotometry method to develop a diagnostic algorithm for blood studies and the content of douglas deepening in women with ovarian tumors. A comparative analysis of the blood of healthy women and patients with ovarian cancer revealed significantly greater optical anisotropy of the latter. Qualitative studies of polarization microscopic blood images revealed a very developed microcrystalline structure. Based on the study of blood and puncture and douglas deepening of healthy women and patients with benign and malignant tumors of the ovaries, using the method of laser polarimetry, experimentally developed and clinically tested photometric and polarization criteria indicating the presence of malignancy of the tumor.

Autologous transplantation of cryopreserved ovarian tissue to induce puberty-the endocrinologists' view.

PubMed

von Wolff, Michael; Stute, Petra; Flück, Christa

2016-12-01

Transplantation of cryopreserved ovarian tissue has been shown to successfully induce pregnancies. Furthermore, puberty may be induced by transplanted ovarian tissue in girls suffering from premature primary ovarian insufficiency (PPOI) due to gonadotoxic therapy. Therefore, the question arises if ovarian tissue cryopreservation should be recommended for puberty induction in prepubertal girls with cancer prior to gonadotoxic therapies. Although this strategy seems to be more natural than administering exogenous steroid sex hormones, there are some disadvantages from the endocrinological point of view. During physiologic puberty, serum estradiol levels increase very slowly, followed by irregular and finally regular ovulations with progesterone production during the luteal phase. PPOI presents as hypergonadotrophic hypogonadism. When transplanting ovarian tissue in girls with PPOI, the elevated gonadotrophins will promote a sudden follicular growth of one or several follicles with a sharp increase of serum estrogen levels and regular ovulations. This will result into an accelerated pubertal development with the risk of overt weight gain, cutaneous striae and premature growth stop possibly leading to psychological implications. Transplantation of cryopreserved ovarian tissue should not be recommended as an alternative to medically induced puberty.

Habitat quality of the coastal southeastern Bering Sea for juvenile flatfishes from the relationships between diet, body condition and prey availability

NASA Astrophysics Data System (ADS)

Yeung, Cynthia; Yang, Mei-Sun

2017-01-01

The distribution and body condition of juvenile northern rock sole (NRS), Lepidopsetta polyxystra, and yellowfin sole (YFS), Limanda aspera, were studied in relation to prey availability across the coastal shelf at the Alaska Peninsula boundary of the eastern Bering Sea (EBS) to assess spatial variability in habitat quality. Juveniles of ≤ 20 cm and adults of ≥ 30 cm total length were collected from bottom trawl catch samples at stations located 10 to 120 km from the Alaska Peninsula coast, and in bottom depths of 28 to 85 m. Stomach contents and stable isotopes of carbon and nitrogen from muscle tissue were analyzed to describe diet composition. The quantity and quality of prey did not significantly affect the distribution of juvenile NRS and YFS. Spatial mismatch between the diet composition and the infauna prey assemblage suggested that prey availability was not limiting across the area, allowing fish to select for prey, presumably to maximize net energy gain. The body condition of juvenile NRS was higher in the eastern section of the area (Bristol Bay) - where they shared spatial and dietary niches with juvenile YFS, than in the west section (Unimak Island) where juvenile YFS were largely absent. A difference in body condition suggests that habitat quality may be higher in Bristol Bay. For NRS, stomach contents and stable isotopes in muscle tissue indicated an ontogenetic diet shift from amphipods to polychaetes from juvenile to adult stages. In contrast, for YFS, amphipods seemed to remain the primary prey and polychaetes the least important prey from juvenile to adult stage. Given that the high prey availability found in this south coastal area of EBS extends to areas across the EBS shelf, favorable habitat for juvenile flatfishes should be extensive. However, much of this potential juvenile habitat is underutilized by NRS, which were mainly limited to Bristol Bay and the Alaska Peninsula, whereas YFS did extend north over 500 km from Bristol Bay along the inner shelf domain (≤ 50 m deep). Abiotic factors, particularly ocean currents and water temperature, may be more significant than prey availability in the spatial distribution of juveniles. Thus, changes in the hydrographic and thermal regime of the EBS are likely to impact juvenile flatfish distribution and habitat productivity.

Glycomics Laboratory for the Development of Ovarian Cancer Biomarkers | Division of Cancer Prevention

Cancer.gov

Ovarian cancer is a silent killer with few early symptoms and advanced disease often present at the time of diagnosis. This cancer is the most lethal of all gynecologic malignancies with over 20,000 new cases diagnosed each year. The 5 year survival rates for ovarian cancer dramatically improve when the disease is diagnosed at an earlier stage. Therefore, the long term goal of

Constitutively active transforming growth factor β receptor 1 in the mouse ovary promotes tumorigenesis

PubMed Central

Gao, Yang; Vincent, David F.; Davis, Anna Jane; Sansom, Owen J.; Bartholin, Laurent; Li, Qinglei

2016-01-01

Despite the well-established tumor suppressive role of TGFβ proteins, depletion of key TGFβ signaling components in the mouse ovary does not induce a growth advantage. To define the role of TGFβ signaling in ovarian tumorigenesis, we created a mouse model expressing a constitutively active TGFβ receptor 1 (TGFBR1) in ovarian somatic cells using conditional gain-of-function approach. Remarkably, these mice developed ovarian sex cord-stromal tumors with complete penetrance, leading to reproductive failure and mortality. The tumors expressed multiple granulosa cell markers and caused elevated serum inhibin and estradiol levels, reminiscent of granulosa cell tumors. Consistent with the tumorigenic effect, overactivation of TGFBR1 altered tumor microenvironment by promoting angiogenesis and enhanced ovarian cell proliferation, accompanied by impaired cell differentiation and dysregulated expression of critical genes in ovarian function. By further exploiting complementary genetic models, we substantiated our finding that constitutively active TGFBR1 is a potent oncogenic switch in mouse granulosa cells. In summary, overactivation of TGFBR1 drives gonadal tumor development. The TGFBR1 constitutively active mouse model phenocopies a number of morphological, hormonal, and molecular features of human granulosa cell tumors and are potentially valuable for preclinical testing of targeted therapies to treat granulosa cell tumors, a class of poorly defined ovarian malignancies. PMID:27344183

Ovarian angiogenesis in polycystic ovary syndrome.

PubMed

Di Pietro, Mariana; Pascuali, Natalia; Parborell, Fernanda; Abramovich, Dalhia

2018-05-01

Polycystic ovary syndrome (PCOS) is the most prevalent endocrine pathology among women in reproductive age. Its main symptoms are oligo or amenorrhea, hyperandrogenism and the presence of ovarian cysts. It is also associated with infertility, obesity and insulin resistance. Mainly due to its heterogeneity, PCOS treatments are directed to manage its symptoms and to prevent associated diseases. The correct formation and regression of blood vessels during each ovarian cycle is indispensable for proper follicular development, ovulation and corpus luteum formation. The importance of these processes opened a new and promising field: ovarian angiogenesis. Vascular alterations characterize numerous pathologies, either with increased, decreased or abnormal angiogenesis. In the last years, several anomalies of ovarian angiogenesis have been described in women with PCOS. Therefore, it has been suggested that these alterations may be associated with the decreased - or lack of - ovulation rates and for the formation of cysts in the PCOS ovaries. Restoration of a proper vessel formation in the ovaries may lead to improved follicular development and ovulation in these patients. In the present review, we attempt to summarize the alterations in ovarian angiogenesis that have been described in women with PCOS. We also discuss the therapeutic approaches aimed to correct these alterations and their beneficial effects on the treatment of infertility in PCOS. © 2018 Society for Reproduction and Fertility.

A putative role for anti-Müllerian hormone (AMH) in optimising ovarian reserve expenditure.

PubMed

Pankhurst, Michael W

2017-04-01

The mammalian ovary has a finite supply of oocytes, which are contained within primordial follicles where they are arrested in a dormant state. The number of primordial follicles in the ovary at puberty is highly variable between females of the same species. Females that enter puberty with a small ovarian reserve are at risk of a shorter reproductive lifespan, as their ovarian reserve is expected to be depleted faster. One of the roles of anti-Müllerian hormone (AMH) is to inhibit primordial follicle activation, which slows the rate at which the ovarian reserve is depleted. A simple interpretation is that the function of AMH is to conserve ovarian reserve. However, the females with the lowest ovarian reserve and the greatest risk of early reserve depletion have the lowest levels of AMH. In contrast, AMH apparently strongly inhibits primordial follicle activation in females with ample ovarian reserve, for reasons that remain unexplained. The rate of primordial follicle activation determines the size of the developing follicle pool, which in turn, determines how many oocytes are available to be selected for ovulation. This review discusses the evidence that AMH regulates the size of the developing follicle pool by altering the rate of primordial follicle activation in a context-dependent manner. The expression patterns of AMH across life are also consistent with changing requirements for primordial follicle activation in the ageing ovary. A potential role of AMH in the fertility of ageing females is proposed herein. © 2017 Society for Endocrinology.

The expression of TP53 pathway-related proteins in ovarian carcinoma transplanted subcutaneously in nude mice.

PubMed

Zhang, S-R; Li, D-B; Xue, J-W

2018-03-01

Given the important functions of TP53 pathway in various biological processes, this study aimed to investigate the expression of TP53 pathway-related proteins in ovarian carcinoma transplanted subcutaneously in nude mice with and without the presence of p53 inhibitor and to explore possible roles of p53 in the development of ovarian cancer. Thirty BALB/c-nu female nude mice were randomly divided into model group, control group and p53 inhibitor group (Pftα group). There were 10 rats in each group. The nude mice were subcutaneously inoculated with human ovarian cancer cell line SKOV3, and the tumor growth was observed. Morphological changes of tumor tissue were observed by hematoxylin and eosin (HE) staining. The mRNA and protein levels of TP53 pathway related factors-p53, p21 and mouse double minute 2 homolog (MDM2) were detected by RT-PCR and Western blot. p53 inhibitor can increase the growth rate of subcutaneously transplanted tumor in nude mice. p53 inhibitor could decrease the expression of p53 and p21 at both mRNA and protein levels and increase the expression of MDM2 at both mRNA and protein levels in ovarian carcinoma transplanted subcutaneously in nude mice. TP53 pathway may play pivotal roles in the development of ovarian cancer and TP53 pathway may be a new target for the treatment of ovarian cancer.

Annual reproductive synchronization in ovary and pineal gland function of female short-nosed fruit bat, Cynopterus sphinx.

PubMed

Haldar, Chandana; Yadav, Rajesh; Alipreeta

2006-08-01

We studied the annual correlation of ovarian activity and pineal gland in relation with seasonal variation and gestation of a tropical zone short-nosed fruit bat Cynopterus sphinx. Female bats showed bimodal polyestry (February/March and September/October) in their reproductive cycle. Plasma estradiol concentration ran parallel with ovarian activity and had an inverse relation with pineal mass and peripheral melatonin concentration. Due to the delayed embryonic development in the uterus (October-March) of female bats, interestingly, the uterine activity did not show a parallel relation with ovarian activity and estradiol level. Further, compared with normal non-pregnant females, melatonin level was high during gestation and delayed embryonic development phase. This suggests that the reproductive synchrony and annual variation in ovarian activity of this nocturnal flying mammal differ from other common tropical mammals. The delayed embryonic development in bats might be an adaptive strategy for the unfavorable conditions of the seasons and might be regulated by high peripheral estradiol and melatonin concentration.

Human ovarian cancer stem/progenitor cells are stimulated by doxorubicin but inhibited by Mullerian inhibiting substance

PubMed Central

Meirelles, Katia; Benedict, Leo Andrew; Dombkowski, David; Pepin, David; Preffer, Frederic I.; Teixeira, Jose; Tanwar, Pradeep Singh; Young, Robert H.; MacLaughlin, David T.; Donahoe, Patricia K.; Wei, Xiaolong

2012-01-01

Women with late-stage ovarian cancer usually develop chemotherapeutic-resistant recurrence. It has been theorized that a rare cancer stem cell, which is responsible for the growth and maintenance of the tumor, is also resistant to conventional chemotherapeutics. We have isolated from multiple ovarian cancer cell lines an ovarian cancer stem cell-enriched population marked by CD44, CD24, and Epcam (3+) and by negative selection for Ecadherin (Ecad−) that comprises less than 1% of cancer cells and has increased colony formation and shorter tumor-free intervals in vivo after limiting dilution. Surprisingly, these cells are not only resistant to chemotherapeutics such as doxorubicin, but also are stimulated by it, as evidenced by the significantly increased number of colonies in treated 3+Ecad− cells. Similarly, proliferation of the 3+Ecad− cells in monolayer increased with treatment, by either doxorubicin or cisplatin, compared with the unseparated or cancer stem cell-depleted 3−Ecad+ cells. However, these cells are sensitive to Mullerian inhibiting substance (MIS), which decreased colony formation. MIS inhibits ovarian cancer cells by inducing G1 arrest of the 3+Ecad− subpopulation through the induction of cyclin-dependent kinase inhibitors. 3+Ecad− cells selectively expressed LIN28, which colocalized by immunofluorescence with the 3+ cancer stem cell markers in the human ovarian carcinoma cell line, OVCAR-5, and is also highly expressed in transgenic murine models of ovarian cancer and in other human ovarian cancer cell lines. These results suggest that chemotherapeutics may be stimulative to cancer stem cells and that selective inhibition of these cells by treating with MIS or targeting LIN28 should be considered in the development of therapeutics. PMID:22308459

Human ovarian cancer stem/progenitor cells are stimulated by doxorubicin but inhibited by Mullerian inhibiting substance.

PubMed

Meirelles, Katia; Benedict, Leo Andrew; Dombkowski, David; Pepin, David; Preffer, Frederic I; Teixeira, Jose; Tanwar, Pradeep Singh; Young, Robert H; MacLaughlin, David T; Donahoe, Patricia K; Wei, Xiaolong

2012-02-14

Women with late-stage ovarian cancer usually develop chemotherapeutic-resistant recurrence. It has been theorized that a rare cancer stem cell, which is responsible for the growth and maintenance of the tumor, is also resistant to conventional chemotherapeutics. We have isolated from multiple ovarian cancer cell lines an ovarian cancer stem cell-enriched population marked by CD44, CD24, and Epcam (3+) and by negative selection for Ecadherin (Ecad-) that comprises less than 1% of cancer cells and has increased colony formation and shorter tumor-free intervals in vivo after limiting dilution. Surprisingly, these cells are not only resistant to chemotherapeutics such as doxorubicin, but also are stimulated by it, as evidenced by the significantly increased number of colonies in treated 3+Ecad- cells. Similarly, proliferation of the 3+Ecad- cells in monolayer increased with treatment, by either doxorubicin or cisplatin, compared with the unseparated or cancer stem cell-depleted 3-Ecad+ cells. However, these cells are sensitive to Mullerian inhibiting substance (MIS), which decreased colony formation. MIS inhibits ovarian cancer cells by inducing G1 arrest of the 3+Ecad- subpopulation through the induction of cyclin-dependent kinase inhibitors. 3+Ecad- cells selectively expressed LIN28, which colocalized by immunofluorescence with the 3+ cancer stem cell markers in the human ovarian carcinoma cell line, OVCAR-5, and is also highly expressed in transgenic murine models of ovarian cancer and in other human ovarian cancer cell lines. These results suggest that chemotherapeutics may be stimulative to cancer stem cells and that selective inhibition of these cells by treating with MIS or targeting LIN28 should be considered in the development of therapeutics.

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

PubMed Central

Terlikowska, Katarzyna M.; Witkowska, Anna M.; Zujko, Malgorzata E.; Dobrzycka, Bozena; Terlikowski, Slawomir J.

2014-01-01

Recent findings on the molecular basis of ovarian cancer development and progression create new opportunities to develop anticancer medications that would affect specific metabolic pathways and decrease side systemic toxicity of conventional treatment. Among new possibilities for cancer chemoprevention, much attention is paid to curcumin—A broad-spectrum anticancer polyphenolic derivative extracted from the rhizome of Curcuma longa L. According to ClinicalTrials.gov at present there are no running pilot studies, which could assess possible therapeutic benefits from curcumin supplementation to patients with primary epithelial ovarian cancer. Therefore, the goal of this review was to evaluate potential preclinical properties of curcumin and its new analogues on the basis of in vivo and in vitro ovarian cancer studies. Curcumin and its different formulations have been shown to display multifunctional mechanisms of anticancer activity, not only in platinum-resistant primary epithelial ovarian cancer, but also in multidrug resistant cancer cells/xenografts models. Curcumin administered together with platinum-taxane chemotherapeutics have been reported to demonstrate synergistic effects, sensitize resistant cells to drugs, and decrease their biologically effective doses. An accumulating body of evidence suggests that curcumin, due to its long-term safety and an excellent profile of side effects should be considered as a beneficial support in ovarian cancer treatment strategies, especially in patients with platinum-resistant primary epithelial recurrent ovarian cancer or multidrug resistant disease. Although the prospect of curcumin and its formulations as anticancer agents in ovarian cancer treatment strategy appears to be challenging, and at the same time promising, there is a further need to evaluate its effectiveness in clinical studies. PMID:25429431

Potential application of curcumin and its analogues in the treatment strategy of patients with primary epithelial ovarian cancer.

PubMed

Terlikowska, Katarzyna M; Witkowska, Anna M; Zujko, Malgorzata E; Dobrzycka, Bozena; Terlikowski, Slawomir J

2014-11-25

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

Parabens Accelerate Ovarian Dysfunction in a 4-Vinylcyclohexene Diepoxide-Induced Ovarian Failure Model

PubMed Central

Lee, Jae-Hwan; Lee, Myeongho; Ahn, Changhwan; Kang, Hee Young; Tran, Dinh Nam; Jeung, Eui-Bae

2017-01-01

Parabens are widely used preservatives in basic necessities such as cosmetic and pharmaceutical products. In previous studies, xenoestrogenic actions of parabens were reported in an immature rat model and a rat pituitary cell line (GH3 cells). The relationship between parabens and ovarian failure has not been described. In the present study, the influence of parabens on ovarian folliculogenesis and steroidogenesis was investigated. A disruptor of ovarian small pre-antral follicles, 4-vinylcyclohexene diepoxide (VCD, 40 mg/kg), was used to induce premature ovarian failure (POF). Methylparaben (MP, 100 mg/kg), propylparaben (PP, 100 mg/kg), and butylparaben (BP, 100 mg/kg) dissolved in corn oil were treated in female 8-week-old Sprague-Dawley rat for 5 weeks. Estrus cycle status was checked daily by vaginal smear test. Ovarian follicle development and steroid synthesis were investigated through real-time PCR and histological analyses. Diestrus phases in the VCD, PP, and BP groups were longer than that in the vehicle group. VCD significantly decreased mRNA level of folliculogenesis-related genes (Foxl2, Kitl and Amh). All parabens significantly increased the Amh mRNA level but unchanged Foxl2 and Kitlg acting in primordial follicles. VCD and MP slightly increased Star and Cyp11a1 levels, which are related to an initial step in steroidogenesis. VCD and parabens induced an increase in FSH levels in serum and significantly decreased the total number of follicles. Increased FSH implies impairment in ovarian function due to VCD or parabens. These results suggest that VCD may suppress both formation and development of follicles. In particular, combined administration of VCD and parabens accelerated inhibition of the follicle-developmental process through elevated AMH level in small antral follicles. PMID:28208728

Genome-Scale Screen for DNA Methylation-Based Detection Markers for Ovarian Cancer

PubMed Central

Houshdaran, Sahar; Shen, Hui; Widschwendter, Martin; Daxenbichler, Günter; Long, Tiffany; Marth, Christian; Laird-Offringa, Ite A.; Press, Michael F.; Dubeau, Louis; Siegmund, Kimberly D.; Wu, Anna H.; Groshen, Susan; Chandavarkar, Uma; Roman, Lynda D.; Berchuck, Andrew; Pearce, Celeste L.; Laird, Peter W.

2011-01-01

Background The identification of sensitive biomarkers for the detection of ovarian cancer is of high clinical relevance for early detection and/or monitoring of disease recurrence. We developed a systematic multi-step biomarker discovery and verification strategy to identify candidate DNA methylation markers for the blood-based detection of ovarian cancer. Methodology/Principal Findings We used the Illumina Infinium platform to analyze the DNA methylation status of 27,578 CpG sites in 41 ovarian tumors. We employed a marker selection strategy that emphasized sensitivity by requiring consistency of methylation across tumors, while achieving specificity by excluding markers with methylation in control leukocyte or serum DNA. Our verification strategy involved testing the ability of identified markers to monitor disease burden in serially collected serum samples from ovarian cancer patients who had undergone surgical tumor resection compared to CA-125 levels. We identified one marker, IFFO1 promoter methylation (IFFO1-M), that is frequently methylated in ovarian tumors and that is rarely detected in the blood of normal controls. When tested in 127 serially collected sera from ovarian cancer patients, IFFO1-M showed post-resection kinetics significantly correlated with serum CA-125 measurements in six out of 16 patients. Conclusions/Significance We implemented an effective marker screening and verification strategy, leading to the identification of IFFO1-M as a blood-based candidate marker for sensitive detection of ovarian cancer. Serum levels of IFFO1-M displayed post-resection kinetics consistent with a reflection of disease burden. We anticipate that IFFO1-M and other candidate markers emerging from this marker development pipeline may provide disease detection capabilities that complement existing biomarkers. PMID:22163280

Demographic, Clinical, and Prognostic Factors of Ovarian Clear Cell Adenocarcinomas According to Endometriosis Status.

PubMed

Schnack, Tine H; Høgdall, Estrid; Thomsen, Lotte Nedergaard; Høgdall, Claus

2017-11-01

Women with endometriosis carry an increased risk for ovarian clear cell adenocarcinomas (CCCs). Clear cell adenocarcinoma may develop from endometriosis lesions. Few studies have compared clinical and prognostic factors and overall survival in patients diagnosed as having CCC according to endometriosis status. Population-based prospectively collected data on CCC with coexisting pelvic (including ovarian; n = 80) and ovarian (n = 46) endometriosis or without endometriosis (n = 95) were obtained through the Danish Gynecological Cancer Database. χ Test, independent-samples t test, logistic regression, Kaplan-Meier test, and Cox regression were used. Statistical tests were 2 sided. P values less than 0.05 were considered statistically significant. Patients with CCC and pelvic or ovarian endometriosis were significantly younger than CCC patients without endometriosis, and a higher proportion of them were nulliparous (28% and 31% vs 17% (P = 0.07 and P = 0.09). Accordingly, a significantly higher proportion of women without endometriosis had given birth to more than 1 child. Interestingly, a significantly higher proportion of patients with ovarian endometriosis had pure CCCs (97.8% vs 82.1%; P = 0.001) as compared with patients without endometriosis. Overall survival was poorer among CCC patients with concomitant ovarian endometriosis (hazard ratio, 2.56 [95% confidence interval, 1.29-5.02], in the multivariate analysis. Age at CCC diagnosis and parity as well as histology differ between CCC patients with and without concomitant endometriosis. Furthermore, CCC patients with concomitant ovarian endometriosis have a poorer prognosis compared with endometriosis-negative CCC patients. These differences warrant further research to determine whether CCCs with and without concomitant endometriosis develop through distinct pathogenic pathways.

Women under 70 who use aspirin daily have a ~10 percent lower risk of developing ovarian cancer.

Cancer.gov

Study found that women under the age of 70 who use aspirin (or non-aspirin NSAIDS) daily or almost daily for at least six months have a ~10 percent lower risk of developing ovarian cancer than women who use it infrequently or not at all.

Development of the ovarian follicular epithelium.

PubMed

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

1999-05-25

A lot is known about the endocrine control of the development of ovarian follicles, but a key question now facing researchers is which molecular and cellular processes take part in control of follicular growth and development. The growth and development of ovarian follicles occurs postnatally and throughout adult life. In this review, we focus on the follicular epithelium (membrana granulosa) and its basal lamina. We discuss a model of how granulosa cells arise from a population of stem cells and then enter different lineages before differentiation. The structure of the epithelium at the antral stage of development is presented, and the effects that follicle growth has on the behavior of the granulosa cells are discussed. Finally, we discuss the evidence that during follicle development the follicular basal lamina changes in composition. This would be expected if the behavior of the granulosa cells changes, or if the permeability of the basal lamina changes. It will be evident that the follicular epithelium has similarities to other epithelia in the body, but that it is more dynamic, as gross changes occur during the course of follicle development. This basic information will be important for the development of future reproductive technologies in both humans and animals, and possibly for understanding polycystic ovarian syndrome in women.

Quantitative analysis of cell-free DNA in ovarian cancer.

PubMed

Shao, Xuefeng; He, Yan; Ji, Min; Chen, Xiaofang; Qi, Jing; Shi, Wei; Hao, Tianbo; Ju, Shaoqing

2015-12-01

The aim of the present study was to investigate the association between cell-free DNA (cf-DNA) levels and clinicopathological characteristics of patients with ovarian cancer using a branched DNA (bDNA) technique, and to determine the value of quantitative cf-DNA detection in assisting with the diagnosis of ovarian cancer. Serum specimens were collected from 36 patients with ovarian cancer on days 1, 3 and 7 following surgery, and additional serum samples were also collected from 22 benign ovarian tumor cases, and 19 healthy, non-cancerous ovaries. bDNA techniques were used to detect serum cf-DNA concentrations. All data were analyzed using SPSS version 18.0. The cf-DNA levels were significantly increased in the ovarian cancer group compared with those of the benign ovarian tumor group and healthy ovarian group (P<0.01). Furthermore, cf-DNA levels were significantly increased in stage III and IV ovarian cancer compared with those of stages I and II (P<0.01). In addition, cf-DNA levels were significantly increased on the first day post-surgery (P<0.01), and subsequently demonstrated a gradual decrease. In the ovarian cancer group, the area under the receiver operating characteristic curve of cf-DNA and the sensitivity were 0.917 and 88.9%, respectively, which was higher than those of cancer antigen 125 (0.724, 75%) and human epididymis protein 4 (0.743, 80.6%). There was a correlation between the levels of serum cf-DNA and the occurrence and development of ovarian cancer in the patients evaluated. bDNA techniques possessed higher sensitivity and specificity than other methods for the detection of serum cf-DNA in patients exhibiting ovarian cancer, and bDNA techniques are more useful for detecting cf-DNA than other factors. Thus, the present study demonstrated the potential value for the use of bDNA as an adjuvant diagnostic method for ovarian cancer.

Ovarian cancer and hormone replacement therapy in the Million Women Study.

PubMed

Beral, Valerie; Bull, Diana; Green, Jane; Reeves, Gillian

2007-05-19

Ovarian cancer is the fourth most common cancer in women in the UK, with about 6700 developing the malignancy and 4600 dying from it every year. However, there is limited information about the risk of ovarian cancer associated with the use of hormone replacement therapy (HRT). 948,576 postmenopausal women from the UK Million Women Study who did not have previous cancer or bilateral oophorectomy were followed-up for an average of 5.3 years for incident ovarian cancer and 6.9 years for death. Information on HRT use was obtained at recruitment and updated where possible. Relative risks for ovarian cancer were calculated, stratified by age and hysterectomy status, and adjusted by area of residence, socioeconomic group, time since menopause, parity, body-mass index, alcohol consumption, and use of oral contraceptives. When they last reported HRT use, 287,143 women (30%) were current users and 186 751 (20%) were past users. During follow-up, 2273 incident ovarian cancers and 1591 deaths from the malignancy were recorded. Current users were significantly more likely to develop and die from ovarian cancer than never users (relative risk 1.20 [95% CI 1.09-1.32; p=0.0002] for incident disease and 1.23 [1.09-1.38; p=0.0006] for death). For current users of HRT, incidence of ovarian cancer increased with increasing duration of use, but did not differ significantly by type of preparation used, its constituents, or mode of administration. Risks associated with HRT varied significantly according to tumour histology (p<0.0001), and in women with epithelial tumours the relative risk for current versus never use of HRT was greater for serous than for mucinous, endometroid, or clear cell tumours (1.53 [1.31-1.79], 0.72 [0.52-1.00], 1.05 [0.77-1.43], or 0.77 [0.48-1.23], respectively). Past users of HRT were not at an increased risk of ovarian cancer (0.98 [0.88-1.11] and 0.97 [0.84-1.11], respectively, for incident and fatal disease). Over 5 years, the standardised incidence rates for ovarian cancer in current and never users of HRT were 2.6 (2.4-2.9) and 2.2 (2.1-2.3) per 1000, respectively-ie, one extra ovarian cancer in roughly 2500 users; death rates were 1.6 (1.4-1.8) and 1.3 (1.2-1.4) per 1000, respectively-ie, one extra ovarian cancer death in roughly 3300 users. Women who use HRT are at an increased risk of both incident and fatal ovarian cancer. Since 1991, use of HRT has resulted in some 1300 additional ovarian cancers and 1000 additional deaths from the malignancy in the UK.

Ovarian ageing: the role of mitochondria in oocytes and follicles.

PubMed

May-Panloup, Pascale; Boucret, Lisa; Chao de la Barca, Juan-Manuel; Desquiret-Dumas, Valérie; Ferré-L'Hotellier, Véronique; Morinière, Catherine; Descamps, Philippe; Procaccio, Vincent; Reynier, Pascal

2016-11-01

There is a great inter-individual variability of ovarian ageing, and almost 20% of patients consulting for infertility show signs of premature ovarian ageing. This feature, taken together with delayed childbearing in modern society, leads to the emergence of age-related ovarian dysfunction concomitantly with the desire for pregnancy. Assisted reproductive technology is frequently inefficacious in cases of ovarian ageing, thus raising the economic, medical and societal costs of the procedures. Ovarian ageing is characterized by quantitative and qualitative alteration of the ovarian oocyte reserve. Mitochondria play a central role in follicular atresia and could be the main target of the ooplasmic factors determining oocyte quality adversely affected by ageing. Indeed, the oocyte is the richest cell of the body in mitochondria and depends largely on these organelles to acquire competence for fertilization and early embryonic development. Moreover, the oocyte ensures the uniparental transmission and stability of the mitochondrial genome across the generations. This review focuses on the role played by mitochondria in ovarian ageing and on the possible consequences over the generations. PubMed was used to search the MEDLINE database for peer-reviewed original articles and reviews concerning mitochondria and ovarian ageing, in animal and human species. Searches were performed using keywords belonging to three groups: 'mitochondria' or 'mitochondrial DNA'; 'ovarian reserve', 'oocyte', 'ovary' or 'cumulus cells'; and 'ageing' or 'ovarian ageing'. These keywords were combined with other search phrases relevant to the topic. References from these articles were used to obtain additional articles. There is a close relationship, in mammalian models and humans, between mitochondria and the decline of oocyte quality with ageing. Qualitatively, ageing-related mitochondrial (mt) DNA instability, which leads to the accumulation of mtDNA mutations in the oocyte, plays a key role in the deterioration of oocyte quality in terms of competence and of the risk of transmitting mitochondrial abnormalities to the offspring. In contrast, some mtDNA haplogroups are protective against the decline of ovarian reserve. Quantitatively, mitochondrial biogenesis is crucial during oogenesis for constituting a mitochondrial pool sufficiently large to allow normal early embryonic development and to avoid the untimely activation of mitochondrial biogenesis. Ovarian ageing also seriously affects the dynamic nature of mitochondrial biogenesis in the surrounding granulosa cells that may provide interesting alternative biomarkers of oocyte quality. A fuller understanding of the involvement of mitochondria in cases of infertility linked to ovarian ageing would contribute to a better management of the disorder in the future. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Genetics Home Reference: fragile X-associated primary ovarian insufficiency

MedlinePlus

... a quarter of them develop the condition. FXPOI accounts for about 4 to 6 percent of all cases of primary ovarian insufficiency in women. Related Information What information about a genetic condition can statistics ...

Ovarian cancer clinical trial endpoints: Society of Gynecologic Oncology white paper.

PubMed

Herzog, Thomas J; Armstrong, Deborah K; Brady, Mark F; Coleman, Robert L; Einstein, Mark H; Monk, Bradley J; Mannel, Robert S; Thigpen, J Tate; Umpierre, Sharee A; Villella, Jeannine A; Alvarez, Ronald D

2014-01-01

To explore the value of multiple clinical endpoints in the unique setting of ovarian cancer. A clinical trial workgroup was established by the Society of Gynecologic Oncology to develop a consensus statement via multiple conference calls, meetings and white paper drafts. Clinical trial endpoints have profound effects on late phase clinical trial design, result interpretation, drug development, and regulatory approval of therapeutics. Selection of the optimal clinical trial endpoint is particularly provocative in ovarian cancer where long overall survival (OS) is observed. The lack of new regulatory approvals and the lack of harmony between regulatory bodies globally for ovarian cancer therapeutics are of concern. The advantages and disadvantages of the numerous endpoints available are herein discussed within the unique context of ovarian cancer where both crossover and post-progression therapies potentially uncouple surrogacy between progression-free survival (PFS) and OS, the two most widely supported and utilized endpoints. The roles of patient reported outcomes (PRO) and health related quality of life (HRQoL) are discussed, but even these widely supported parameters are affected by the unique characteristics of ovarian cancer where a significant percentage of patients may be asymptomatic. Original data regarding the endpoint preferences of ovarian cancer advocates is presented. Endpoint selection in ovarian cancer clinical trials should reflect the impact on disease burden and unique characteristics of the treatment cohort while reflecting true patient benefit. Both OS and PFS have led to regulatory approvals and are clinically important. OS remains the most objective and accepted endpoint because it is least vulnerable to bias; however, the feasibility of OS in ovarian cancer is compromised by the requirement for large trial size, prolonged time-line for final analysis, and potential for unintended loss of treatment effect from active post-progression therapies. A large magnitude of effect in PFS improvement should establish benefit, and further communication with regulatory authorities to clarify acceptable endpoints should be undertaken. Copyright © 2013. Published by Elsevier Inc.

Ovarian cancer clinical trial endpoints: Society of Gynecologic Oncology white paper

PubMed Central

Herzog, Thomas J.; Armstrong, Deborah K.; Brady, Mark F.; Coleman, Robert L.; Einstein, Mark H.; Monk, Bradley J.; Mannel, Robert S.; Thigpen, J. Tate; Umpierre, Sharee A.; Villella, Jeannine A.; Alvarez, Ronald D.

2015-01-01

Objective To explore the value of multiple clinical endpoints in the unique setting of ovarian cancer. Methods A clinical trial workgroup was established by the Society of Gynecologic Oncology to develop a consensus statement via multiple conference calls, meetings and white paper drafts. Results Clinical trial endpoints have profound effects on late phase clinical trial design, result interpretation, drug development, and regulatory approval of therapeutics. Selection of the optimal clinical trial endpoint is particularly provocative in ovarian cancer where long overall survival (OS) is observed. The lack of new regulatory approvals and the lack of harmony between regulatory bodies globally for ovarian cancer therapeutics are of concern. The advantages and disadvantages of the numerous endpoints available are herein discussed within the unique context of ovarian cancer where both crossover and post-progression therapies potentially uncouple surrogacy between progression-free survival (PFS) and OS, the two most widely supported and utilized endpoints. The roles of patient reported outcomes (PRO) and health related quality of life (HRQoL) are discussed, but even these widely supported parameters are affected by the unique characteristics of ovarian cancer where a significant percentage of patients may be asymptomatic. Original data regarding the endpoint preferences of ovarian cancer advocates is presented. Conclusions Endpoint selection in ovarian cancer clinical trials should reflect the impact on disease burden and unique characteristics of the treatment cohort while reflecting true patient benefit. Both OS and PFS have led to regulatory approvals and are clinically important. OS remains the most objective and accepted endpoint because it is least vulnerable to bias; however, the feasibility of OS in ovarian cancer is compromised by the requirement for large trial size, prolonged time-line for final analysis, and potential for unintended loss of treatment effect from active post-progression therapies. A large magnitude of effect in PFS improvement should establish benefit, and further communication with regulatory authorities to clarify acceptable endpoints should be undertaken. PMID:24239753

77 FR 46641 - Fisheries of the Exclusive Economic Zone Off Alaska; “Other Flatfish” in the Bering Sea and...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-06

...NMFS apportions amounts of the non-specified reserve to the initial total allowable catch (ITAC) of ``other flatfish'' in the Bering Sea and Aleutian Islands management area (BSAI) and Greenland turbot in the Aleutian Island subarea of the BSAI. This action is necessary to allow the fisheries to continue operating. It is intended to promote the goals and objectives of the fishery management plan for the BSAI.

Detecting critical periods in larval flatfish populations

NASA Astrophysics Data System (ADS)

Chambers, R. Christopher; Witting, David A.; Lewis, Stephen J.

2001-06-01

We evaluate the time-course of deaths and evidence of periods of increased mortality (i.e., critical periods) in laboratory populations of larval flatfish. First, we make the distinction between age-at-death and abundance-at-time data for fish larvae, the latter being typical in studies of natural populations. Next, we describe an experimental investigation of age- and temperature-dependent mortality in larval winter flounder, Pseudopleuronectes americanus. The survivorship curves of these populations differed significantly in both the magnitude and time-course of mortality among the four water temperatures evaluated (7, 10, 13, and 16°C). Mortality was highest in the cooler temperatures and concentrated in the third quarter of larval life, largely concurrent with settlement of surviving members of the cohort. Among the statistical methods for analysing survival data, the proportional-hazards model with time-varying covariates proved best at capturing the patterns of age-specific mortalities. We conclude that fair appraisals of recruitment hypotheses which are predicated on periods of high, age-specific mortality that vary with environmental conditions (e.g., Hjort's critical period hypothesis) will require: (1) data that are based on age, not time; (2) data that are of higher temporal resolution than commonly available at present and (3) analytical methods that are sensitive to irregularities in survivorship curves. We suggest four research approaches for evaluating critical periods in nature.

The toxic mechanism of high lethality of herbicide butachlor in marine flatfish flounder, Paralichthys olivaceus

NASA Astrophysics Data System (ADS)

Guo, Huarong; Yin, Licheng; Zhang, Shicui; Feng, Wenrong

2010-09-01

The toxic mechanism of herbicide butachlor to induce extremely high lethality in marine flatfish flounder, Paralichthys Olivaceus, was analyzed by histopathological examination, antioxidant enzymes activities and ATP content assay. Histopathological examination of gill, liver and kidney of exposed fishes showed that gill was a target organ of butachlor. The butachlor seriously impaired the respiration of gills by a series of lesions such as edema, lifting and detachment of lamellar epithelium, breakdown of pillar cells, and blood congestion. The dysfunction of gill respiration caused suffocation to the exposed flounder with extremely high acute lethality. Antioxidant enzyme activity assay of the in vitro cultured flounder gill (FG) cells exposed to butachlor indicated that butachlor markedly inhibited the antioxidant enzyme activities of Superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX). Furthermore, along with the decline of antioxidant enzyme activities, ATP content in the exposed FG cells decreased, too. This infers that the oxidative stress induced by butachlor can inhibit the production of cellular ATP. Similar decrease of ATP content was also observed in the exposed flounder gill tissues. Taken together, as in FG cells, butachlor possibly induced a short supply of ATP in pillar cells by inhibiting the antioxidant enzyme activities and then affecting the contractibility of the pillar cells, which in turn resulted in the blood congestion and suffocation of exposed flounder.

Identification of the main processes underlying ecosystem functioning in the Eastern English Channel, with a focus on flatfish species, as revealed through the application of the Atlantis end-to-end model

NASA Astrophysics Data System (ADS)

Girardin, Raphaël; Fulton, Elizabeth A.; Lehuta, Sigrid; Rolland, Marie; Thébaud, Olivier; Travers-Trolet, Morgane; Vermard, Youen; Marchal, Paul

2018-02-01

The ecosystem model Atlantis was used to investigate the key dynamics and processes that structure the Eastern English Channel ecosystem, with a particular focus on two commercial flatfish species, sole (Solea solea) and plaice (Pleuronectes platessa). This complex model was parameterized with data collected from diverse sources (a literature review, survey data, as well as landings and stock assessment information) and tuned so both simulated biomass and catch fit 2002-2011 observations. Here, the outputs are mainly presented for the two focus species and for some other vertebrates found to be important in the trophic network. The calibration process revealed the importance of coastal areas in the Eastern English Channel and of nutrient inputs from estuaries: a lack of river nutrients decreases the productivity of nursery grounds and adversely affects the production of sole and plaice. The role of discards in the trophic network is also highlighted. While sole and plaice did not have a strong influence on the trophic network of vertebrates, they are important predators for benthic invertebrates and compete for food with crustaceans, whiting (Merlangius merlangus) and other demersal fish. We also found that two key species, cod (Gadus morhua) and whiting, thoroughly structured the Eastern English Channel trophic network.

Identification of miRNAs during mouse postnatal ovarian development and superovulation.

PubMed

Khan, Hamid Ali; Zhao, Yi; Wang, Li; Li, Qian; Du, Yu-Ai; Dan, Yi; Huo, Li-Jun

2015-07-08

MicroRNAs are small noncoding RNAs that play critical roles in regulation of gene expression in wide array of tissues including the ovary through sequence complementarity at post-transcriptional level. Tight regulation of multitude of genes involved in ovarian development and folliculogenesis could be regulated at transcription level by these miRNAs. Therefore, tissue specific miRNAs identification is considered a key step towards understanding the role of miRNAs in biological processes. To investigate the role of microRNAs during ovarian development and folliculogenesis we sequenced eight different libraries using Illumina deep sequencing technology. Different developmental stages were selected to explore miRNAs expression pattern at different stages of gonadal maturation with/without treatment of PMSG/hCG for superovulation. From massive sequencing reads, clean reads of 16-26 bp were selected for further analysis of differential expression analysis and novel microRNA annotation. Expression analysis of all miRNAs at different developmental stages showed that some miRNAs were present ubiquitously while others were differentially expressed at different stages. Among differentially expressed miRNAs we reported 61 miRNAs with a fold change of more than 2 at different developmental stages among all libraries. Among the up-regulated miRNAs, mmu-mir-1298 had the highest fold change with 4.025 while mmu-mir-150 was down-regulated more than 3 fold. Furthermore, we found 2659 target genes for 20 differentially expressed microRNAs using seven different target predictions programs (DIANA-mT, miRanda, miRDB, miRWalk, RNAhybrid, PICTAR5, TargetScan). Analysis of the predicted targets showed certain ovary specific genes targeted by single or multiple microRNAs. Furthermore, pathway annotation and Gene ontology showed involvement of these microRNAs in basic cellular process. These results suggest the presence of different miRNAs at different stages of ovarian development and superovulation. Potential role of these microRNAs was elucidated using bioinformatics tools in regulation of different pathways, biological functions and cellular components underlying ovarian development and superovulation. These results provide a framework for extended analysis of miRNAs and their roles during ovarian development and superovulation. Furthermore, this study provides a base for characterization of individual miRNAs to discover their role in ovarian development and female fertility.

Role of serum miRNAs in the prediction of ovarian hyperstimulation syndrome in polycystic ovarian syndrome patients.

PubMed

Zhao, Chun; Liu, Xiaoguang; Shi, Zhonghua; Zhang, Jing; Zhang, Junqiang; Jia, Xuemei; Ling, Xiufeng

2015-01-01

Polycystic ovarian syndrome (PCOS) causes a significantly increased risk of ovarian hyperstimulation syndrome (OHSS). Here, we focused on the altered expression of serum miRNAs and their predictive value for OHSS in PCOS patients. We used the TaqMan low density array followed by individual quantitative reverse transcription-polymerase chain reaction to identify and validate the expression of serum miRNAs in PCOS patients likely to develop severe OHSS. The miR-16 and miR-223 expression levels were significantly reduced in the patients who were likely to develop severe OHSS than in the control subjects who were likely to develop mild or no OHSS. The sensitivity and specificity of the basal LH, basal LH/FSH, and body mass index (BMI) as OHSS predictors were also evaluated. miR-16 was the most efficient for OHSS prediction as it yielded the highest AUC. Logistic binary regression analyses revealed a positive association of miR-223 and BMI. Serum miRNAs are differentially expressed in PCOS patients likely to suffer from severe OHSS. We identified and validated two serum miRNAs that have potential for use as novel noninvasive biomarkers to accurately predict OHSS before controlled ovarian hyperstimulation (COH) for PCOS patients. © 2015 S. Karger AG, Basel.

Ovarian Cancer: Prevention, Detection and Treatment of the Disease and Its Recurrence. Molecular Mechanisms and Personalized Medicine Meeting Report

PubMed Central

Modugno, Francesmary; Edwards, Robert P.

2012-01-01

Objective To review the current understanding of the underlying molecular, biologic and genetic mechanisms involved in ovarian cancer development and how these mechanisms can be targets for prevention, detection and treatment of the disease and its recurrence. Methods In May 2012, we convened a meeting of researchers, clinicians and consumer advocates to review the state of current knowledge on molecular mechanisms and identify fruitful areas for further investigations. Results The meeting consisted of seven scientific sessions, ranging from Epidemiology, Early Detection, and Biology to Therapeutics and Quality of Life. Sessions consisted of talks and panel discussions by international leaders in ovarian cancer research. A special career-development session by the CDMRP Department of Defense Ovarian Cancer Academy as well as an oral abstract and poster session showcased promising new research by junior scientists. Conclusions Technological advances in the last decade have increased our knowledge of the molecular mechanisms involved in a host of biological activities related to ovarian cancer. Understanding the role these mechanisms play in cancer initiation and progression will help lead to the development of prevention and treatment modalities that can be personalized to each patient, thereby helping to overcome this highly-fatal malignancy. PMID:23013733

Papillary Tubal Hyperplasia. The Putative Precursor of Ovarian Atypical Proliferative (Borderline) Serous Tumors, Noninvasive Implants and Endosalpingiosis

PubMed Central

Kurman, Robert J.; Vang, Russell; Junge, Jette; Hannibal, Charlotte Gerd; Kjaer, Susanne K.; Shih, Ie-Ming

2011-01-01

In contrast to the controversy regarding the terminology and behavior of ovarian noninvasive low-grade serous tumors (atypical proliferative serous tumor [APST] and serous borderline tumor [SBT]), little attention has been directed to their origin. Similarly, until recently, proliferative lesions in the fallopian tube have not been extensively studied. The recent proposal that ovarian high-grade serous carcinomas are derived from intraepithelial carcinoma in the fallopian tube prompted us to evaluate the possible role of the fallopian tube in the genesis of low-grade serous tumors. We have identified a lesion, designated “papillary tubal hyperplasia (PTH)”, characterized by small rounded clusters of tubal epithelial cells and small papillae, with or without associated psammoma bodies, that are present within the tubal lumen and which are frequently associated with APSTs. Twenty-two cases in this study were selected from a population-based study in Denmark of approximately 1000 patients with low-grade ovarian serous tumors in whom implants were identified on the fallopian tube. Seven additional cases were seen recently in consultation at The Johns Hopkins Hospital (JHH). These 7 cases were not associated with an ovarian tumor. Papillary tubal hyperplasia was found in 20 (91%) of the 22 cases in the Danish study. Based on this association of PTH with APSTs with implants and the close morphologic resemblance of PTH, not only to the primary ovarian APSTs but also to the noninvasive epithelial implants and endosalpingiosis, we speculate that the small papillae and clusters of cells from the fallopian tubes implant on ovarian and peritoneal surfaces to produce these lesions. The 7 JHH cases of PTH that were not associated with an ovarian tumor support the view that PTH is the likely precursor lesion. We propose a model for the development of ovarian and extraovarian low-grade serous proliferations (APST, noninvasive epithelial implants and endosalpingiosis) that postulates that all of these lesions are derived from PTH, which appears to be induced by chronic inflammation. If this hypothesis is confirmed, then it can be concluded that low- and high-grade ovarian tumors develop from tubal epithelium and involve the ovary secondarily. PMID:21997682

Induction of a menopausal state alters the growth and histology of ovarian tumors in a mouse model of ovarian cancer.

PubMed

Laviolette, Laura A; Ethier, Jean-François; Senterman, Mary K; Devine, Patrick J; Vanderhyden, Barbara C

2011-05-01

Ovarian cancer is often diagnosed in women after menopause when the levels of the serum gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are increased because of the depletion of growing follicles within the ovary. The ability of FSH and LH to modulate the disease has not been well studied owing to a lack of physiologically relevant models of ovarian cancer. In this study, 4-vinylcyclohexene diepoxide (VCD) was used to deplete ovarian follicles and increase the levels of circulating FSH and LH in the tgCAG-LS-TAg mouse model of ovarian cancer. VCD-induced follicle depletion was performed either before or after induction of the oncogene SV40 large and small T-antigens in the ovarian surface epithelial cells of tgCAG-LS-TAg mice, which was mediated by the intrabursal delivery of an adenovirus expressing Cre recombinase (AdCre). tgCAG-LS-TAg mice injected with AdCre developed undifferentiated ovarian tumors with mixed epithelial and stromal components and some features of sex cord stromal tumors. Treatment with VCD before or after AdCre injection yielded tumors of similar histology, but with the unique appearance of Sertoli cell nests. In mice treated with VCD before the induction of tumorigenesis, the ovarian tumors tended to grow more slowly. The human ovarian cancer cell lines SKOV3 and OVCAR3 responded similarly to increased levels of gonadotropins in a second model of menopause, growing more slowly in ovariectomized mice compared with cycling controls. These results suggest that follicle depletion and increased gonadotropin levels can alter the histology and the rate of growth of ovarian tumors.

In vivo three-dimensional optical coherence tomography and multiphoton microscopy in a mouse model of ovarian neoplasia

NASA Astrophysics Data System (ADS)

Watson, Jennifer M.; Marion, Samuel L.; Rice, Photini Faith; Bentley, David L.; Besselsen, David; Utzinger, Urs; Hoyer, Patricia B.; Barton, Jennifer K.

2013-03-01

Our goal is to use optical coherence tomography (OCT) and multiphoton microscopy (MPM) to detect early tumor development in a mouse model of ovarian neoplasia. We hope to use information regarding early tumor development to create a diagnostic test for high-risk patients. In this study we collect in vivo images using OCT, second harmonic generation and two-photon excited fluorescence from non-vinylcyclohexene diepoxide (VCD)-dosed and VCD-dosed mice. VCD causes follicular apoptosis (simulating menopause) and leads to tumor development. Using OCT and MPM we visualized the ovarian microstructure and were able to see differences between non-VCD-dosed and VCD-dosed animals. This leads us to believe that OCT and MPM may be useful for detecting changes due to early tumor development.

Dual modality imaging of a novel rat model of ovarian carcinogenesis

NASA Astrophysics Data System (ADS)

Kanter, Elizabeth; Walker, Ross; Marion, Sam; Brewer, Molly A.; Hoyer, Patricia B.; Barton, Jennifer K.

2006-07-01

Ovarian cancer is the fifth leading cause of cancer death in women, in part because of the limited knowledge about early stage disease. We develop a novel rat model of ovarian cancer and perform a pilot study to examine the harvested ovaries with complementary optical imaging modalities. Rats are exposed to repeated daily dosing (20 days) with 4-vinylcyclohexene diepoxide (VCD) to cause early ovarian failure (model for postmenopause), and ovaries are directly exposed to 7,12-dimethylbenz(a)anthracene (DMBA) to cause abnormal ovarian proliferation and neoplasia. Harvested ovaries are examined with optical coherence tomography (OCT) and light-induced fluorescence (LIF) at one, three, and five months post-DMBA treatment. VCD causes complete ovarian follicle depletion within 8 months after onset of dosing. DMBA induces abnormal size, cysts, and neoplastic changes. OCT successfully visualizes normal and abnormal structures (e.g., cysts, bursa, follicular remnant degeneration) and the LIF spectra show statistically significant changes in the ratio of average emission intensity at 390:450 nm between VCD-treated ovaries and both normal cycling and neoplastic DMBA-treated ovaries. Overall, this pilot study demonstrates the feasibility of both the novel animal model for ovarian cancer and the ability of optical imaging techniques to visualize ovarian function and health.

Pycnogenol reduces talc-induced neoplastic transformation in human ovarian cell cultures.

PubMed

Buz'Zard, Amber R; Lau, Benjamin H S

2007-06-01

Talc and poor diet have been suggested to increase the risk of developing ovarian cancer; which can be reduced by a diet rich in fruit and vegetables. Talc is ubiquitous despite concern about its safety, role as a possible carcinogen and known ability to cause irritation and inflammation. It was recently shown that Pycnogenol (Pyc; a proprietary mixture of water-soluble bioflavonoids extracted from French maritime pine bark) was selectively toxic to established malignant ovarian germ cells. This study investigated talc-induced carcinogenesis and Pyc-induced chemoprevention. Normal human epithelial and granulosa ovarian cell lines and polymorphonuclear neutrophils (PMN) were treated with talc, or pretreated with Pyc then talc. Cell viability, reactive oxygen species (ROS) generation and neoplastic transformation by soft agar assay were measured. Talc increased proliferation, induced neoplastic transformation and increased ROS generation time-dependently in the ovarian cells and dose-dependently in the PMN. Pretreatment with Pyc inhibited the talc-induced increase in proliferation, decreased the number of transformed colonies and decreased the ROS generation in the ovarian cells. The data suggest that talc may contribute to ovarian neoplastic transformation and Pyc reduced the talc-induced transformation. Taken together, Pyc may prove to be a potent chemopreventative agent against ovarian carcinogenesis. (c) 2007 John Wiley & Sons, Ltd.

Modeling Human Epithelial Ovarian Cancer in Mice by Alteration of Expression of the BRCA1 and/or p53 Genes

DTIC Science & Technology

2008-02-01

injection developed neoplasms with a frequency of ~20% (9/42 mice). Only one ovarian neoplasm was identified and that was hilar cell tumor of the ovary. In...neoplasms were identified; one ovarian leiomyosarcoma (excision of both Brca1 and p53 alleles was confirmed by PCR amplification) and one ovarian hilar ...0 (0/42) 0 (0/41) 0 (0/18) Hilar cell tumor of ovary 2 (1/46) 3 (1/39) 0 (0/42) 0 (0/41) 0 (0/18) Lymphoma 0 (0/46) 3 (1/39) 0 (0/42) 5 (2/41) 6 (1

Cyclin Dependent Kinase Inhibitors as Targets in Ovarian Cancer

DTIC Science & Technology

2005-10-01

STATEMENT Approved for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT The objective of this proposal is to develop gene ...have identified key genes that may be effective targets in ovarian cancer therapy. The first three projects seek to identify alterations in these genes ...that allow for high expression of our key gene (s) in ovarian cancer cells but minimal expression in normal tissues. 15. SUBJECT TERMS Cell cycle control

Ovarian function after autologous bone marrow transplantation in childhood: high-dose busulfan is a major cause of ovarian failure.

PubMed

Teinturier, C; Hartmann, O; Valteau-Couanet, D; Benhamou, E; Bougneres, P F

1998-11-01

We studied pubertal status and ovarian function in 21 girls aged 11-21 years who had earlier received 1.2-13 years (median 7 years) high-dose chemotherapy and autologous BMT without TBI for malignant tumors. Ten of them were given busulfan (600 mg/m2) and melphalan (140 mg/m2) with or without cyclophosphamide (3.6 g/m2). Eleven others did not receive busulfan. Twelve girls (57%) had clinical and hormonal evidence of ovarian failure. Among nine others who had completed normal puberty, six had normal gonadotropin levels, one had elevated gonadotropin levels and two had gonadotropin levels at the upper limit of normal. The 10 girls who received busulfan all developed severe and persistent ovarian failure. High-dose busulfan is therefore a major cause of ovarian failure even when given in the prepubertal period. These findings emphasize the need for long-term endocrine follow-up of these patients in order to initiate estrogen replacement therapy.

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.

Evolutionary pressure on reproductive strategies in flatfish and groundfish: Relevant concepts and methodological advancements

NASA Astrophysics Data System (ADS)

Kjesbu, O. S.; Witthames, P. R.

2007-07-01

Flatfish and groundfish show many similarities in reproductive strategies and tactics, both in types present and in responses to fishing pressure or changes in their environment. Over the last 20-30 years the reproduction of Atlantic cod Gadus morhua, Atlantic halibut Hippoglossus hippoglossus, plaice Pleuronectes platessa, sole Solea solea, and turbot Scophthalmus maximus have been extensively studied in the North Atlantic. For cod, halibut and turbot, the research has progressed rapidly due to interest from the aquaculture industry. Extensive overexploitation over many years in combination with climate change represents a potential evolutionary pressure towards changes in growth, lower age at maturity, increased fecundity, smaller egg size (and thereby larval size) and change in spawning time. Early sexual maturity/precocious maturation is also seen in aquaculture and is problematic economically due to a reduction in fillet production. In this paper information is reviewed from studies on both wild and captive populations in experiments, the latter considered important because overexploitation, such as observed in the North Sea, often reduces the natural dynamics in growth and reproduction and complicates collection of sufficiently large samples. Evidence from laboratory experiments demonstrates the inherent plasticity of fecundity production and how this is controlled by food availability and length of photoperiod, while recent information from field studies demonstrates the evolution of genotypes in response to fishing mortality. Today several laboratories have adopted modern techniques for analysis of reproductive investments (fecundity, atresia and sperm characterisation) in controlled experimental situations to explore the effect of temperature or other environmental parameters (such as salinity) on reproduction. These developments, in combination with the rapid implementation of molecular techniques, should make it possible in the future to present highly precise information on reproductive potential, both at the individual and stock level. Of particular interest, and a major goal, would be to dissociate genetic and phenotypic control of reproductive traits arising from a better understanding of gene expression in captive populations.

Effect of estradiol on the expression of angiogenic factors in epithelial ovarian cancer.

PubMed

Valladares, Macarena; Plaza-Parrochia, Francisca; Lépez, Macarena; López, Daniela; Gabler, Fernando; Gayan, Patricio; Selman, Alberto; Vega, Margarita; Romero, Carmen

2017-11-01

Ovarian cancer presents a high angiogenesis (formation of new blood vessels) regulated by pro-angiogenic factors, mainly vascular endothelial growth factor (VEGF) and nerve growth factor (NGF). An association between endogenous levels of estrogen and increased risk of developing ovarian cancer has been reported. Estrogen action is mediated by the binding to its specific receptors (ERα and ERβ), altered ERα/ERβ ratio may constitute a marker of ovarian carcinogenesis progression. To determine the effect of estradiol through ERα on the expression of NGF and VEGF in epithelial ovarian cancer (EOC). Levels of phosphorylated estrogen receptor alpha (pERα) were evaluated in well, moderate and poorly differentiated EOC samples (EOC-I, EOC-II, EOC-III). Additionally, ovarian cancer explants were stimulated with NGF (0, 10 and 100 ng/ml) and ERα, ERβ and pERα levels were detected. Finally, human ovarian surface epithelial (HOSE) and epithelial ovarian cancer (A2780) cell lines were stimulated with estradiol, where NGF and VEGF protein levels were evaluated. In tissues, ERs were detected being pERα levels significantly increased in EOC-III samples compared with EOC-I (p<0.05). Additionally, ovarian explants treated with NGF increased pERα levels meanwhile total ERα and ERβ levels did not change. Cell lines stimulated with estradiol revealed an increase of NGF and VEGF protein levels (p<0.05). Estradiol has a positive effect on pro-angiogenic factors such as NGF and VEGF expression in EOC, probably through the activation of ERα; generating a positive loop induced by NGF increasing pERα levels in epithelial ovarian cells.

Cigarette smoking and the risk of epithelial ovarian cancer.

PubMed

Franks, A L; Lee, N C; Kendrick, J S; Rubin, G L; Layde, P M

1987-07-01

Cigarette smoking may affect each of the currently proposed mechanisms of ovarian carcinogenesis. Whether cigarette smoking has any effect on the development of ovarian cancer has not been adequately evaluated. To study this issue, the authors examined data from the Cancer and Steroid Hormone Study, a multicenter, case-control study of gynecologic cancers conducted between December 1, 1980, and December 31, 1982, in eight geographic areas of the United States. This analysis utilized data on 494 women with newly diagnosed epithelial ovarian cancer and 4,238 population-based control women 20-54 years of age. There was no association of epithelial ovarian cancer with dose of cigarette smoking, age smoking started, time since smoking started, or time since smoking last occurred. Simultaneous adjustment for age, parity, history of oral contraceptive use, and other potentially confounding factors did not alter these results.

Internet-Based Group Intervention for Ovarian Cancer Survivors: Feasibility and Preliminary Results

PubMed Central

Kinner, Ellen M; Armer, Jessica S; McGregor, Bonnie A; Duffecy, Jennifer; Leighton, Susan; Corden, Marya E; Gauthier Mullady, Janine; Penedo, Frank J

2018-01-01

Background Development of psychosocial group interventions for ovarian cancer survivors has been limited. Drawing from elements of cognitive-behavioral stress management (CBSM), mindfulness-based stress reduction (MBSR), and acceptance and commitment therapy (ACT), we developed and conducted preliminary testing of an Internet-based group intervention tailored specifically to meet the needs of ovarian cancer survivors. The Internet-based platform facilitated home delivery of the psychosocial intervention to a group of cancer survivors for whom attending face-to-face programs could be difficult given their physical limitations and the small number of ovarian cancer survivors at any one treatment site. Objective The aim of this study was to develop, optimize, and assess the usability, acceptability, feasibility, and preliminary intended effects of an Internet-based group stress management intervention for ovarian cancer survivors delivered via a tablet or laptop. Methods In total, 9 ovarian cancer survivors provided feedback during usability testing. Subsequently, 19 survivors participated in 5 waves of field testing of the 10-week group intervention led by 2 psychologists. The group met weekly for 2 hours via an Internet-based videoconference platform. Structured interviews and weekly evaluations were used to elicit feedback on the website and intervention content. Before and after the intervention, measures of mood, quality of life (QOL), perceived stress, sleep, and social support were administered. Paired t tests were used to examine changes in psychosocial measures over time. Results Usability results indicated that participants (n=9) performed basic tablet functions quickly with no errors and performed website functions easily with a low frequency of errors. In the field trial (n=19), across 5 groups, the 10-week intervention was well attended. Perceived stress (P=.03) and ovarian cancer-specific QOL (P=.01) both improved significantly during the course of the intervention. Trends toward decreased distress (P=.18) and greater physical (P=.05) and functional well-being (P=.06) were also observed. Qualitative interviews revealed that the most common obstacles participants experienced were technical issues and the time commitment for practicing the techniques taught in the program. Participants reported that the intervention helped them to overcome a sense of isolation and that they appreciated the ability to participate at home. Conclusions An Internet-based group intervention tailored specifically for ovarian cancer survivors is highly usable and acceptable with moderate levels of feasibility. Preliminary psychosocial outcomes indicate decreases in perceived stress and improvements in ovarian cancer-specific QOL following the intervention. A randomized clinical trial is needed to demonstrate the efficacy of this promising intervention for ovarian cancer survivors. PMID:29335233

Dietary fat intake and risk of epithelial ovarian cancer: a meta-analysis of 6,689 subjects from 8 observational studies.

PubMed

Huncharek, M; Kupelnick, B

2001-01-01

The etiology of epithelial ovarian cancer is unknown. Prior work suggests that high dietary fat intake is associated with an increased risk of this tumor, although this association remains speculative. A meta-analysis was performed to evaluate this suspected relationship. Using previously described methods, a protocol was developed for a meta-analysis examining the association between high vs. low dietary fat intake and the risk of epithelial ovarian cancer. Literature search techniques, study inclusion criteria, and statistical procedures were prospectively defined. Data from observational studies were pooled using a general variance-based meta-analytic method employing confidence intervals (CI) previously described by Greenland. The outcome of interest was a summary relative risk (RRs) reflecting the risk of ovarian cancer associated with high vs. low dietary fat intake. Sensitivity analyses were performed when necessary to evaluate any observed statistical heterogeneity. The literature search yielded 8 observational studies enrolling 6,689 subjects. Data were stratified into three dietary fat intake categories: total fat, animal fat, and saturated fat. Initial tests for statistical homogeneity demonstrated that hospital-based studies accounted for observed heterogeneity possibly because of selection bias. Accounting for this, an RRs was calculated for high vs. low total fat intake, yielding a value of 1.24 (95% CI = 1.07-1.43), a statistically significant result. That is, high total fat intake is associated with a 24% increased risk of ovarian cancer development. The RRs for high saturated fat intake was 1.20 (95% CI = 1.04-1.39), suggesting a 20% increased risk of ovarian cancer among subjects with these dietary habits. High vs. low animal fat diet gave an RRs of 1.70 (95% CI = 1.43-2.03), consistent with a statistically significant 70% increased ovarian cancer risk. High dietary fat intake appears to represent a significant risk factor for the development of ovarian cancer. The magnitude of this risk associated with total fat and saturated fat is rather modest. Ovarian cancer risk associated with high animal fat intake appears significantly greater than that associated with the other types of fat intake studied, although this requires confirmation via larger analyses. Further work is needed to clarify factors that may modify the effects of dietary fat in vivo.

Risk of metachronous ovarian cancer after ovarian conservation in young women with stage I cervical cancer.

PubMed

Matsuo, Koji; Machida, Hiroko; Horowitz, Max P; Shahzad, Mian M K; Guntupalli, Saketh R; Roman, Lynda D; Wright, Jason D

2017-11-01

While there is an increasing trend of ovarian conservation at the time of surgical treatment for young women with stage I cervical cancer, the risk for subsequent ovarian cancer after ovarian conservation has not been well studied. We sought to examine the incidence of and risk factors for metachronous ovarian cancer among young women with stage I cervical cancer who had ovarian conservation at the time of hysterectomy. The Surveillance, Epidemiology, and End Results Program was used to identify women aged <50 years who underwent hysterectomy with ovarian conservation for stage I cervical cancer from 1983 through 2013 (n = 4365). Time-dependent analysis was performed for ovarian cancer risk after cervical cancer diagnosis. Mean age at cervical cancer diagnosis was 37 years, and the majority of patients had stage IA disease (68.2%) and squamous histology (72.9%). Median follow-up time was 10.8 years, and there were 13 women who developed metachronous ovarian cancer. The 10- and 20-year cumulative incidences of metachronous ovarian cancer were 0.2% (95% confidence interval, 0.1-0.4) and 0.5% (95% confidence interval, 0.2-0.8), respectively. Mean age at the time of diagnosis of metachronous ovarian cancer was 47.5 years, and stage III-IV disease was seen in 55.6%. Age (≥45 vs <45 years, hazard ratio, 4.22; 95% confidence interval, 1.16-15.4; P = .018), ethnicity (non-white vs white, hazard ratio, 4.29; 95% confidence interval, 1.31-14.0; P = .009), cervical cancer histology (adenocarcinoma or adenosquamous vs squamous, hazard ratio, 3.50; 95% confidence interval, 1.17-10.5; P = .028), and adjuvant radiotherapy use (yes vs no, hazard ratio, 3.69; 95% confidence interval, 1.01-13.4; P = .034) were significantly associated with metachronous ovarian cancer risk. The presence of multiple risk factors was associated with a significantly increased risk of metachronous ovarian cancer compared to the no risk factor group: 1 risk factor (hazard ratio range, 2.96-8.43), 2 risk factors (hazard ratio range, 16.6-31.0), and 3-4 risk factors (hazard ratio range, 62.3-109), respectively. Metachronous ovarian cancer risk after ovarian conservation for women with stage I cervical cancer is <1%. Older age, non-white ethnicity, adenocarcinoma or adenosquamous histology, and adjuvant radiotherapy may be associated with an increased metachronous ovarian cancer risk. Copyright © 2017 Elsevier Inc. All rights reserved.

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

2018-04-11

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

Awareness of symptoms and risk factors of ovarian cancer in a population of women and healthcare providers.

PubMed

Goldstein, Carol L; Susman, Ellen; Lockwood, Suzy; Medlin, Erin E; Behbakht, Kian

2015-04-01

Awareness of ovarian cancer among women and healthcare providers is understudied. An early awareness of ovarian cancer may lead to early detection and treatment of ovarian cancer. The purpose of this study was to determine the level of that awareness among a sample of women and providers. Written surveys were developed by the authors based on available literature and were administered to women (n = 857) and healthcare providers (n = 188) attending or volunteering at a community health fair. Chi-square tests for independence and z tests were used for analysis. Healthcare providers were significantly more likely to identify the symptoms and risk factors for ovarian cancer. Forty percent of women reported being at least slightly familiar with the symptoms of ovarian cancer. Women who were familiar with symptoms were significantly more likely to identify symptoms and risk factors correctly and to report symptoms immediately to a provider. Identification of symptoms among healthcare providers ranged from 59%-93%. Identification of ovarian cancer symptoms and risk factors is poor among women, and knowledge deficits are present in providers. Increasing familiarity and awareness could lead to improvements in early diagnosis.

TAC management in North Sea flatfish fisheries

NASA Astrophysics Data System (ADS)

Daan, Niels

1997-11-01

The Common Fisheries Policy of the European Union adopted in 1983 is primarily focused on a science-based TAC management system with fixed national quota shares. The quality of the assessments of plaice and sole, the consistency of the scientific advice, the congruency of the management decisions, and the enforcement of the regulations are reviewed over a 15-year period. The conclusion is that there have been problems at each level, with the ultimate effect that the policy has not been able to restrict fishing mortality and that the level of overexploitation has only increased. It is argued that the present TAC system has created more problems than it has resolved. Attention is drawn to the autonomic economic developments within the fishery and to the potential for managing the fishery more effectively from the cost side rather than the profit side.

Involvement of opioid peptides in the regulation of reproduction in the prawn Penaeus indicus

NASA Astrophysics Data System (ADS)

Sreenivasula Reddy, P.

The possible involvement of an endogenous opioid system in the regulation of ovarian development in the prawn Penaeus indicus was investigated. Injection of leucine-enkephalin significantly increased the ovarian index and oocyte diameter in a dose-dependent manner. In contrast, injection of methionine-enkephalin significantly decreased the ovarian index and oocyte diameters. These results provide evidence to support the hypothesis that an opioid system is involved in the regulation of reproduction in crustaceans.

COX-1 Suppression and Follicle Depletion in the Etiology of Menopause-Associated Ovarian Cancer

DTIC Science & Technology

2008-10-01

form (8), and cause growth inhibition and apoptosis in ovarian cancer cell lines (9). However, the link between morphological inhibition and...of the c-kit receptor. Genes Dev 1990;4:390-400. 2. Mintz B. Embryological development of primordial germ-cells in the mouse: influence of a new...708–14. 12 Rodriguez GC, Walmer DK, Cline M, et al. Effect of progestin on the ovarian epithelium of macaques: cancer prevention through apoptosis

Comparative Proteomic Profiling Reveals Molecular Characteristics Associated with Oogenesis and Oocyte Maturation during Ovarian Development of Bactrocera dorsalis (Hendel)

PubMed Central

Li, Ran; Zhang, Meng-Yi; Liu, Yu-Wei; Zhang, Zheng; Smagghe, Guy; Wang, Jin-Jun

2017-01-01

Time-dependent expression of proteins in ovary is important to understand oogenesis in insects. Here, we profiled the proteomes of developing ovaries from Bactrocera dorsalis (Hendel) to obtain information about ovarian development with particular emphasis on differentially expressed proteins (DEPs) involved in oogenesis. A total of 4838 proteins were identified with an average peptide number of 8.15 and sequence coverage of 20.79%. Quantitative proteomic analysis showed that a total of 612 and 196 proteins were differentially expressed in developing and mature ovaries, respectively. Furthermore, 153, 196 and 59 potential target proteins were highly expressed in early, vitellogenic and mature ovaries and most tested DEPs had the similar trends consistent with the respective transcriptional profiles. These proteins were abundantly expressed in pre-vitellogenic and vitellogenic stages, including tropomyosin, vitellogenin, eukaryotic translation initiation factor, heat shock protein, importin protein, vitelline membrane protein, and chorion protein. Several hormone and signal pathway related proteins were also identified during ovarian development including piRNA, notch, insulin, juvenile, and ecdysone hormone signal pathways. This is the first report of a global ovary proteome of a tephritid fruit fly, and may contribute to understanding the complicate processes of ovarian development and exploring the potentially novel pest control targets. PMID:28665301

Genetic zygosity of mature ovarian teratomas, struma ovarii, and ovarian carcinoids.

PubMed

Kato, Noriko; Sakamoto, Kazuhiro; Murakami, Koutaro; Iwasaki, Yuri; Kamataki, Akihisa; Kurose, Akira

2018-02-17

Although ovarian monodermal teratomas, including struma ovarii and carcinoids, are closely associated with mature teratomas, their genetic basis is poorly understood. A series of mature and monodermal ovarian teratomas were analyzed by short tandem repeat genotyping to evaluate their genetic zygosity and its associations. Informative DNA genotyping data were obtained for ten mature teratomas, six struma ovarii, and three carcinoids (one insular, one trabecular, and one mucinous). A homozygous genotype was present in five of the ten (50%) mature teratomas, three of the six (50%) struma ovarii, and one of the three (33%) ovarian carcinoids. There was no significant difference in genetic zygosity between mature and monodermal teratomas. Patients' age was not correlated with the genetic zygosity: the youngest age in the homozygous tumor group of patients was 4 years. It is suggested that an oocyte after meiosis I, which has escaped from meiotic arrest, is a significant cause of these tumors. Although one mature teratoma was a rare case with lactating adenoma-like breast tissue, its genetic zygosity was concordant with that of the surrounding teratomatous tissue. In one ovarian carcinoid, the carcinoid and accompanying teratomatous components showed matching zygosity at all but one locus: the carcinoid was heterozygous but teratoma was homozygous at one pericentromeric locus. This suggests that not all carcinoids are secondary neoplasms arising from a fully developed mature teratoma: some are neoplasms deviating from a developing mature teratoma.

The role of mTOR in ovarian cancer, polycystic ovary syndrome and ovarian aging.

PubMed

Liu, Jin; Wu, Dai-Chao; Qu, Li-Hua; Liao, Hong-Qing; Li, Mei-Xiang

2018-05-12

The mammalian target of rapamycin, mTOR, is a serine-threonine protein kinase downstream of the phosphatidylinositol 3-kinase (PI3K)-AKT axis. The pathway can regulate cell growth, proliferation, and survival by activating ribosomal kinases. Recent studies have implicated the mTOR signaling pathway in ovarian neoplasms, polycystic ovary syndrome (PCOS) and premature ovarian failure (POF). Preclinical investigations have demonstrated that the PI3K/AKT/mTOR pathway is frequently activated in the control of various ovarian functions. mTOR allows cancer cells to escape the normal biochemical system and regulates the balance between apoptosis and survival. Some recent studies have suggested that involvement of the mTOR signaling system is an important pathophysiological basis of PCOS. Overexpression of the mTOR pathway can impair the interaction of cumulus cells, lead to insulin resistance, and affect the growth of follicles directly. The roles of mTOR signaling in follicular development have been extensively studied in recent years; abnormalities in this process lead to a series of pathologies such as POF and infertility. To improve understanding of the role of the mTOR signaling pathway in the pathogenesis and development of ovarian diseases, here we review the roles of mTOR signaling in such diseases and discuss the corresponding therapeutic strategies that target this pathway. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

Dihydroartemisinin selectively inhibits PDGFRα-positive ovarian cancer growth and metastasis through inducing degradation of PDGFRα protein

PubMed Central

Li, Xiaoguang; Ba, Qian; Liu, Yanling; Yue, Qingxi; Chen, Peizhan; Li, Jingquan; Zhang, Haibing; Ying, Hao; Ding, Qiurong; Song, Haiyun; Liu, Hong; Zhang, Ruiwen; Wang, Hui

2017-01-01

To develop traditional medicines as modern pharmacotherapies, understanding their molecular mechanisms of action can be very helpful. We have recently reported that Artemisinin and its derivatives, which are clinically used anti-malarial drugs, have significant effects against ovarian cancer, but the direct molecular targets and related combination therapy have been unclear. Herein, we report that dihydroartemisinin, one of the most active derivatives of Artemisinin, directly targets platelet-derived growth factor receptor-alpha (PDGFRα) to inhibit ovarian cancer cell growth and metastasis. Dihydroartemisinin directly binds to the intercellular domain of PDGFRα, reducing its protein stability by accelerating its ubiquitin-mediated degradation, which further inactivates downstream phosphoinositide 3-Kinase and mitogen-activated protein kinase pathways and subsequently represses epithelial–mesenchymal transition, inhibiting cell growth and metastasis of PDGFRα-positive ovarian cancer in vitro and in vivo. A combinational treatment reveals that dihydroartemisinin sensitizes ovarian cancer cells to PDGFR inhibitors. Our clinical study also finds that PDGFRα is overexpressed and positively correlated with high grade and metastasis in human ovarian cancer. Considering that Artemisinin compounds are currently clinically used drugs with favorable safety profiles, the results from this study will potentiate their use in combination with clinically used PDGFRα inhibitors, leading to maximal therapeutic efficacy with minimal adverse effects in PDGFRα-positive cancer patients. These findings also shed high light on future development of novel Artemisinin-based targeted therapy. PMID:29387451

Dihydroartemisinin selectively inhibits PDGFRα-positive ovarian cancer growth and metastasis through inducing degradation of PDGFRα protein.

PubMed

Li, Xiaoguang; Ba, Qian; Liu, Yanling; Yue, Qingxi; Chen, Peizhan; Li, Jingquan; Zhang, Haibing; Ying, Hao; Ding, Qiurong; Song, Haiyun; Liu, Hong; Zhang, Ruiwen; Wang, Hui

2017-01-01

To develop traditional medicines as modern pharmacotherapies, understanding their molecular mechanisms of action can be very helpful. We have recently reported that Artemisinin and its derivatives, which are clinically used anti-malarial drugs, have significant effects against ovarian cancer, but the direct molecular targets and related combination therapy have been unclear. Herein, we report that dihydroartemisinin, one of the most active derivatives of Artemisinin, directly targets platelet-derived growth factor receptor-alpha (PDGFRα) to inhibit ovarian cancer cell growth and metastasis. Dihydroartemisinin directly binds to the intercellular domain of PDGFRα, reducing its protein stability by accelerating its ubiquitin-mediated degradation, which further inactivates downstream phosphoinositide 3-Kinase and mitogen-activated protein kinase pathways and subsequently represses epithelial-mesenchymal transition, inhibiting cell growth and metastasis of PDGFRα-positive ovarian cancer in vitro and in vivo . A combinational treatment reveals that dihydroartemisinin sensitizes ovarian cancer cells to PDGFR inhibitors. Our clinical study also finds that PDGFRα is overexpressed and positively correlated with high grade and metastasis in human ovarian cancer. Considering that Artemisinin compounds are currently clinically used drugs with favorable safety profiles, the results from this study will potentiate their use in combination with clinically used PDGFRα inhibitors, leading to maximal therapeutic efficacy with minimal adverse effects in PDGFRα-positive cancer patients. These findings also shed high light on future development of novel Artemisinin-based targeted therapy.

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.

Habitat Suitability Index Models: Juvenile English sole

USGS Publications Warehouse

Toole, Christopher L.; Barnhart, Roger A.; Onuf, Christopher P.

1987-01-01

English sole (Parophrys vetulus) is one of the major commercial groundfish species caught along the Pacific coast. Landings in the United States and Canada averaged 4,947 t/yr between 1975 and 1984, placing it third in importance among flatfish caught by Pacific coast trawlers (Pacific Marine Fisheries Commission 1985). Juvenile English sole are also among the most abundant fishes in many bays and estuaries along the Pacific (Westrheim 1955; Sopher 1974; Ambrose 1976; Rogers 1985). The English sole is not an important recreational species.

Kisspeptin level in the aging ovary is regulated by the sympathetic nervous system.

PubMed

Fernandois, Daniela; Cruz, Gonzalo; Na, Eun Kyung; Lara, Hernán E; Paredes, Alfonso H

2017-01-01

Previous work has demonstrated that the increase in the activity of sympathetic nerves, which occurs during the subfertility period in female rats, causes an increase in follicular cyst development and impairs follicular development. In addition, the increase in ovarian sympathetic activity of aged rats correlates with an increased expression of kisspeptin (KISS1) in the ovary. This increase in KISS1 could participate in the decrease in follicular development that occurs during the subfertility period. We aimed to determine whether the blockade of ovarian sympathetic tone prevents the increase in KISS1 expression during reproductive aging and improves follicular development. We performed 2 experiments in rats: (1) an in vivo blockade of beta-adrenergic receptor with propranolol (5.0 mg/kg) and (2) an ovarian surgical denervation to modulate the sympathetic system at these ages. We measured Kisspeptin and follicle-stimulating hormone receptor (FSHR) mRNA and protein levels by qRT-PCR and western blot and counted primordial, primary and secondary follicles at 8, 10 and 12 months of age. The results showed that ovarian KISS1 decreased but FSHR increased after both propranolol administration and the surgical denervation in rats of 8, 10 and 12 months of age. An increase in FSHR was related to an increase in the number of smaller secondary follicles and a decreased number of primordial follicles at 8, 10 and 12 months of age. These results suggest that intraovarian KISS1 is regulated by sympathetic nerves via a beta-adrenergic receptor and participates locally in ovarian follicular development in reproductive aging. © 2017 Society for Endocrinology.

BMP signalling in human fetal ovary somatic cells is modulated in a gene-specific fashion by GREM1 and GREM2

PubMed Central

Bayne, Rosemary A.; Donnachie, Douglas J.; Kinnell, Hazel L.; Childs, Andrew J.; Anderson, Richard A.

2016-01-01

STUDY QUESTION Do changes in the expression of bone morphogenetic proteins (BMPs) 2 and 4, and their antagonists Gremlin1 (GREM1) and Gremlin2 (GREM2) during human fetal ovarian development impact on BMP pathway activity and lead to changes in gene expression that may influence the fate and/or function of ovarian somatic cells? STUDY FINDING BMPs 2 and 4 differentially regulate gene expression in cultured human fetal ovarian somatic cells. Expression of some, but not all BMP target genes is antagonised by GREM1 and GREM2, indicating the existence of a mechanism to fine-tune BMP signal intensity in the ovary. Leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5), a marker of immature ovarian somatic cells, is identified as a novel transcriptional target of BMP4. WHAT IS KNOWN ALREADY Extensive re-organisation of the germ and somatic cell populations in the feto-neonatal ovary culminates in the formation of primordial follicles, which provide the basis for a female's future fertility. BMP growth factors play important roles at many stages of ovarian development and function. GREM1, an extracellular antagonist of BMP signalling, regulates the timing of primordial follicle formation in the mouse ovary, and mRNA levels of BMP4 decrease while those of BMP2 increase prior to follicle formation in the human fetal ovary. STUDY DESIGN, SAMPLES/MATERIALS, METHODS Expression of genes encoding BMP pathway components, BMP antagonists and markers of ovarian somatic cells were determined by quantitative (q)RT-PCR in human fetal ovaries (from 8 to 21 weeks gestation) and fetal ovary-derived somatic cell cultures. Ovarian expression of GREM1 protein was confirmed by immunoblotting. Primary human fetal ovarian somatic cell cultures were derived from disaggregated ovaries by differential adhesion and cultured in the presence of recombinant human BMP2 or BMP4, with or without the addition of GREM1 or GREM2. MAIN RESULTS AND THE ROLE OF CHANCE We demonstrate that the expression of BMP antagonists GREM1, GREM2 and CHRD  increases in the lead-up to primordial follicle formation in the human fetal ovary, and that the BMP pathway is active in cultured ovarian somatic cells. This leads to differential changes in the expression of a number of genes, some of which are further modulated by GREM1 and/or GREM2. The positive transcriptional regulation of LGR5 (a marker of less differentiated somatic cells) by BMP4 in vitro suggests that increasing levels of GREM1 and reduced levels of BMP4 as the ovary develops in vivo may act to reduce LGR5 levels and allow pre-granulosa cell differentiation. LIMITATIONS, REASONS FOR CAUTION While we have demonstrated that markers of different somatic cell types are expressed in the cultured ovarian somatic cells, their proportions may not represent the same cells in the intact ovary which also contains germ cells. WIDER IMPLICATIONS OF THE FINDINGS This study extends previous work identifying germ cells as targets of ovarian BMP signalling, and suggests BMPs may regulate the development of both germ and somatic cells in the developing ovary around the time of follicle formation. LARGE SCALE DATA Not applicable. STUDY FUNDING/COMPETING INTERESTS This work was supported by The UK Medical Research Council (Grant No.: G1100357 to RAA), and Medical Research Scotland (Grant No. 345FRG to AJC). The authors have no competing interests to declare. PMID:27385727

BMP signalling in human fetal ovary somatic cells is modulated in a gene-specific fashion by GREM1 and GREM2.

PubMed

Bayne, Rosemary A; Donnachie, Douglas J; Kinnell, Hazel L; Childs, Andrew J; Anderson, Richard A

2016-09-01

Do changes in the expression of bone morphogenetic proteins (BMPs) 2 and 4, and their antagonists Gremlin1 (GREM1) and Gremlin2 (GREM2) during human fetal ovarian development impact on BMP pathway activity and lead to changes in gene expression that may influence the fate and/or function of ovarian somatic cells? BMPs 2 and 4 differentially regulate gene expression in cultured human fetal ovarian somatic cells. Expression of some, but not all BMP target genes is antagonised by GREM1 and GREM2, indicating the existence of a mechanism to fine-tune BMP signal intensity in the ovary. Leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5), a marker of immature ovarian somatic cells, is identified as a novel transcriptional target of BMP4. Extensive re-organisation of the germ and somatic cell populations in the feto-neonatal ovary culminates in the formation of primordial follicles, which provide the basis for a female's future fertility. BMP growth factors play important roles at many stages of ovarian development and function. GREM1, an extracellular antagonist of BMP signalling, regulates the timing of primordial follicle formation in the mouse ovary, and mRNA levels of BMP4 decrease while those of BMP2 increase prior to follicle formation in the human fetal ovary. Expression of genes encoding BMP pathway components, BMP antagonists and markers of ovarian somatic cells were determined by quantitative (q)RT-PCR in human fetal ovaries (from 8 to 21 weeks gestation) and fetal ovary-derived somatic cell cultures. Ovarian expression of GREM1 protein was confirmed by immunoblotting. Primary human fetal ovarian somatic cell cultures were derived from disaggregated ovaries by differential adhesion and cultured in the presence of recombinant human BMP2 or BMP4, with or without the addition of GREM1 or GREM2. We demonstrate that the expression of BMP antagonists GREM1, GREM2 and CHRD  increases in the lead-up to primordial follicle formation in the human fetal ovary, and that the BMP pathway is active in cultured ovarian somatic cells. This leads to differential changes in the expression of a number of genes, some of which are further modulated by GREM1 and/or GREM2. The positive transcriptional regulation of LGR5 (a marker of less differentiated somatic cells) by BMP4 in vitro suggests that increasing levels of GREM1 and reduced levels of BMP4 as the ovary develops in vivo may act to reduce LGR5 levels and allow pre-granulosa cell differentiation. While we have demonstrated that markers of different somatic cell types are expressed in the cultured ovarian somatic cells, their proportions may not represent the same cells in the intact ovary which also contains germ cells. This study extends previous work identifying germ cells as targets of ovarian BMP signalling, and suggests BMPs may regulate the development of both germ and somatic cells in the developing ovary around the time of follicle formation. Not applicable. This work was supported by The UK Medical Research Council (Grant No.: G1100357 to RAA), and Medical Research Scotland (Grant No. 345FRG to AJC). The authors have no competing interests to declare. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.

Discovery – BRCA Connection to Breast and Ovarian Cancer

Cancer.gov

NCI-funded research helped identify inherited BRCA1 and BRCA2 genetic mutations and their connection to breast and ovarian cancer. From this research, a screening test was also developed to help patients make informed decisions about their health.

Functional Assessment of Synoptic Pathology Reporting for Ovarian Cancer.

PubMed

Słodkowska, Janina; Cierniak, Szczepan; Patera, Janusz; Kopik, Jarosław; Baranowski, Włodzimierz; Markiewicz, Tomasz; Murawski, Piotr; Buda, Irmina; Kozłowski, Wojciech

2016-01-01

Ovarian cancer has one of the highest death/incidence rates and is commonly diagnosed at an advanced stage. In the recent WHO classification, new histotypes were classified which respond differently to chemotherapy. The e-standardized synoptic cancer pathology reports offer the clinicians essential and reliable information. The aim of our project was to develop an e-template for the standardized synoptic pathology reporting of ovarian carcinoma [based on the checklist of the College of American Pathologists (CAP) and the recent WHO/FIGO classification] to introduce a uniform and improved quality of cancer pathology reports. A functional and qualitative evaluation of the synoptic reporting was performed. An indispensable module for e-synoptic reporting was developed and integrated into the Hospital Information System (HIS). The electronic pathology system used a standardized structure with drop-down lists of defined elements to ensure completeness and consistency of reporting practices with the required guidelines. All ovarian cancer pathology reports (partial and final) with the corresponding glass slides selected from a 1-year current workflow were revised for the standard structured reports, and 42 tumors [13 borderline tumors and 29 carcinomas (mainly serous)] were included in the study. Analysis of the reports for completeness against the CAP checklist standard showed a lack of pTNM staging in 80% of the partial or final unstructured reports; ICD-O coding was missing in 83%. Much less frequently missed or unstated data were: ovarian capsule infiltration, angioinvasion and implant evaluation. The e-records of ovarian tumors were supplemented with digital macro- and micro-images and whole-slide images. The e-module developed for synoptic ovarian cancer pathology reporting was easily incorporated into HIS.CGM CliniNet and facilitated comprehensive reporting; it also provided open access to the database for concerned recipients. The e-synoptic pathology reports appeared more accurate, clear and conclusive than traditional narrative reports. Standardizing structured reporting and electronic tools allows open access and downstream utilization of pathology data for clinicians and tumor registries. © 2016 S. Karger AG, Basel.

Role of oxidative stress in epithelial ovarian cancer in Egyptian patients.

PubMed

Ramadan, Asmaa; Hemida, Reda; Nowara, Ahmed; Eissa, Laila A; El-Gayar, Amal M

2017-05-01

Ovarian cancer has the highest mortality rate amongst all gynecologic malignancies. 90% of the cases are epithelial ovarian cancer (EOC). Ovarian cancer associated with reduction in the serum level of antioxidants super oxide dismutase (SOD) and glutathione peroxidase (GPX) and increasing in the serum level of Malondialdehyde (MDA). To find correlation between oxidative stress and epithelial ovarian cancer. In this cross-sectional study fifty-six female patients with EOC, twenty four female patients with benign ovarian tumors and ten healthy females were included in the current research study where serum level of SOD, GPX and MDA were measured. Levels of SOD and GPX were found to be significantly higher in benign group when compared with malignant group (P1<0.05). There was a significant negative association between malignancy and each of SOD and GPX (p<0.05). While there was a significant positive association between malignancy and MDA (p<0.05). There was a significant negative correlation between tumor stage and level of SOD and GPX (p<0.05). Moreover, there was a significance positive correlation between tumor stage and MDA (p< 0.05). Patients with epithelial ovarian cancer has decreased preoperative serum level of SOD and GPX antioxidants and increased level of MDA. These findings were associated with advanced tumor stage. The study confirmed the role of oxidative stress in development of epithelial ovarian cancer.

HGF-independent regulation of MET and GAB1 by nonreceptor tyrosine kinase FER potentiates metastasis in ovarian cancer

PubMed Central

Fan, Gaofeng; Zhang, Siwei; Gao, Yan; Greer, Peter A.; Tonks, Nicholas K.

2016-01-01

Ovarian cancer cells disseminate readily within the peritoneal cavity, which promotes metastasis, and are often resistant to chemotherapy. Ovarian cancer patients tend to present with advanced disease, which also limits treatment options; consequently, new therapies are required. The oncoprotein tyrosine kinase MET, which is the receptor for hepatocyte growth factor (HGF), has been implicated in ovarian tumorigenesis and has been the subject of extensive drug development efforts. Here, we report a novel ligand- and autophosphorylation-independent activation of MET through the nonreceptor tyrosine kinase feline sarcoma-related (FER). We demonstrated that the levels of FER were elevated in ovarian cancer cell lines relative to those in immortalized normal surface epithelial cells and that suppression of FER attenuated the motility and invasive properties of these cancer cells. Furthermore, loss of FER impaired the metastasis of ovarian cancer cells in vivo. Mechanistically, we demonstrated that FER phosphorylated a signaling site in MET: Tyr1349. This enhanced activation of RAC1/PAK1 and promoted a kinase-independent scaffolding function that led to recruitment and phosphorylation of GAB1 and the specific activation of the SHP2–ERK signaling pathway. Overall, this analysis provides new insights into signaling events that underlie metastasis in ovarian cancer cells, consistent with a prometastatic role of FER and highlighting its potential as a novel therapeutic target for metastatic ovarian cancer. PMID:27401557

Epigenetic regulation of RGS2 (Regulator of G-protein signaling 2) in chemoresistant ovarian cancer cells.

PubMed

Cacan, Ercan

2017-06-01

Regulator of G-protein signaling 2 (RGS2) is a GTPase-activating protein functioning as an inhibitor of G-protein coupled receptors (GPCRs). RGS2 dysregulation was implicated in solid tumour development and RGS2 downregulation has been reported in prostate and ovarian cancer progression. However, the molecular mechanism by which RGS2 expression is suppressed in ovarian cancer remains unknown. The expression and epigenetic regulation of RGS2 in chemosensitive and chemoresistant ovarian cancer cells were determined by qRT-PCR and chromatin immunoprecipitation assays, respectively. In the present study, the molecular mechanisms contributing to the loss of RGS2 expression were determined in ovarian cancer. The data indicated that suppression of RGS2 gene in chemoresistant ovarian cancer cells, in part, due to accumulation of histone deacetylases (HDACs) and DNA methyltransferase I (DNMT1) at the promoter region of RGS2. Inhibition of HDACs or DNMTs significantly increases RGS2 expression. These results suggest that epigenetic changes in histone modifications and DNA methylation may contribute to the loss of RGS2 expression in chemoresistant ovarian cancer cells. The results further suggest that class I HDACs and DNMT1 contribute to the suppression of RGS2 during acquired chemoresistance and support growing evidence that inhibition of HDACs/DNMTs represents novel therapeutic approaches to overcome ovarian cancer chemoresistance.

Mass spectrometric profiling reveals association of N-glycan patterns with epithelial ovarian cancer progression.

PubMed

Chen, Huanhuan; Deng, Zaian; Huang, Chuncui; Wu, Hongmei; Zhao, Xia; Li, Yan

2017-07-01

Aberrant changes of N-glycan modifications on proteins have been linked to various diseases including different cancers, suggesting possible avenue for exploring their etiologies based on N-glycomic analysis. Changes in N-glycan patterns during epithelial ovarian cancer development have so far been investigated mainly using serum, plasma, ascites, and cell lines. However, changes in patterns of N-glycans in tumor tissues during epithelial ovarian cancer progression have remained largely undefined. To investigate whether changes in N-glycan patterns correlate with oncogenesis and progression of epithelial ovarian cancer, we profiled N-glycans from formalin-fixed paraffin-embedded tissue slides using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and quantitatively compared among different pathological grades of epithelial ovarian cancer and healthy controls. Our results show that among the 80 compositions of N-glycan detected, expression levels of high-mannose type were higher in epithelial ovarian cancer samples than that observed in healthy controls, accompanied by reduced levels of hybrid-type glycans. By applying receiver operating characteristic analysis, we show that a combined panel composed of four high-mannose and three fucosylated neutral complex N-glycans allows for good discrimination of epithelial ovarian cancer from healthy controls. Furthermore, using a statistical analysis of variance assay, we found that different N-glycan patterns, including 2 high-mannose-type, 2 fucosylated and sialylated complex structures, and 10 fucosylated neutral complex N-glycans, exhibited specific changes in N-glycan abundance across epithelial ovarian cancer grades. Together, our results provide strong evidence that N-glycomic changes are a strong indicator for epithelial ovarian cancer pathological grades and should provide avenues to identify novel biomarkers for epithelial ovarian cancer diagnosis and monitoring.

Short-term culture of adult bovine ovarian tissues: chorioallantoic membrane (CAM) vs. traditional in vitro culture systems.

PubMed

Beck, Kylie; Singh, Jaswant; Dar, Mohammad Arshud; Anzar, Muhammad

2018-03-09

A suitable culture system is important for follicle growth in adult bovine ovarian tissue. This study aimed to assess the avian chorioallantoic membrane (CAM) for short-term culture of adult bovine ovarian tissues compared with a traditional in vitro culture system. Ovarian cortical tissues (1-2 mm 3 ), collected from slaughtered adult cows, were randomly assigned to control, CAM or in vitro culture groups. In the control group, ovarian tissues were fixed with paraformaldehyde without culture. In CAM and in vitro culture groups, the ovarian tissues were cultured for up to 5 days and then fixed. Ovarian tissues were examined on culture days 0, 1, 3 and 5 for angiogenesis, follicle morphology and growth. In all groups, primordial and growing (healthy and atretic) follicle densities were determined. In the CAM culture, the avian blood vessel density increased (p < 0.01) over time with a decline (p < 0.001) in the bovine blood vessel density. Healthy primordial, atretic primordial and healthy growing follicle densities were higher (p < 0.05) in CAM-cultured ovarian tissues than in vitro-cultured tissues. Regardless of the culture system, the density of healthy primordial follicles decreased (p < 0.001) over time with an increase in healthy growing follicles on day 3 (p < 0.01) and an increase in atretic (primordial and growing) follicles during the 5-day culture period (p < 0.001). The proportions of healthy primordial and atretic growing follicles were also affected by culture day (p < 0.001). The CAM culture in chick embryos supported the bovine ovarian tissue grafts for 3 days demonstrating that CAM can be used as a satisfactory short-term culture system to assess ovarian tissue health, and to study follicle activation and development.

Restoring Ovarian Endocrine Function with Encapsulated Ovarian Allograft in Immune Competent Mice

PubMed Central

David, Anu; Day, James Ronald; Cichon, Alexa Leigh; Lefferts, Adam; Cascalho, Marilia; Shikanov, Ariella

2017-01-01

Premature ovarian insufficiency (POI) is a major complication of cytotoxic treatments due to extreme ovarian sensitivity to chemotherapy and radiation. In pediatric cancer patients modern therapy has improved the long-term survival to over 80% in the United States. However, these cancer survivors face long-term health problems related to treatment toxicity. In female cancer survivors POI leads to sterility, along with the consequences of estrogen deficiency such as premature osteopenia, muscle wasting, accelerated cardiovascular diseases and a vast array of other health and developmental problems. These long-lasting effects are particularly significant for young girls reaching puberty. As such, restoring ovarian endocrine function is paramount in this population. In the present study, we evaluated the feasibility of restoring ovarian endocrine function in ovariectomized mice by transplanting syngeneic and allogeneic ovarian tissue encapsulated in alginate capsules or TheraCyte®. Histological analysis of the implants retrieved after 7 and 30 days' post implantation showed follicular development up to the secondary and antral stages in both syngeneic and allogeneic implants. Implantation of syngeneic and allogeneic ovarian grafts encapsulated in TheraCyte devices restored ovarian endocrine function, which was confirmed by decreased serum FSH levels from 60 to 70 ng/mL in ovariectomized mice to 30–40 ng/mL 30 days after implantation. Absence of allo-MHC—specific IgG and IgM antibodies in the sera of implanted mice with allogeneic ovarian tissue encapsulated in TheraCyte indicate that the implants did not evoke an allo-immune response, while the allogeneic controls were rejected 21 days after implantation. Our results show that TheraCyte effectively isolates the graft from immune recognition but also supports follicular growth. PMID:28028710

Restoring Ovarian Endocrine Function with Encapsulated Ovarian Allograft in Immune Competent Mice.

PubMed

David, Anu; Day, James Ronald; Cichon, Alexa Leigh; Lefferts, Adam; Cascalho, Marilia; Shikanov, Ariella

2017-07-01

Premature ovarian insufficiency (POI) is a major complication of cytotoxic treatments due to extreme ovarian sensitivity to chemotherapy and radiation. In pediatric cancer patients modern therapy has improved the long-term survival to over 80% in the United States. However, these cancer survivors face long-term health problems related to treatment toxicity. In female cancer survivors POI leads to sterility, along with the consequences of estrogen deficiency such as premature osteopenia, muscle wasting, accelerated cardiovascular diseases and a vast array of other health and developmental problems. These long-lasting effects are particularly significant for young girls reaching puberty. As such, restoring ovarian endocrine function is paramount in this population. In the present study, we evaluated the feasibility of restoring ovarian endocrine function in ovariectomized mice by transplanting syngeneic and allogeneic ovarian tissue encapsulated in alginate capsules or TheraCyte ® . Histological analysis of the implants retrieved after 7 and 30 days' post implantation showed follicular development up to the secondary and antral stages in both syngeneic and allogeneic implants. Implantation of syngeneic and allogeneic ovarian grafts encapsulated in TheraCyte devices restored ovarian endocrine function, which was confirmed by decreased serum FSH levels from 60 to 70 ng/mL in ovariectomized mice to 30-40 ng/mL 30 days after implantation. Absence of allo-MHC-specific IgG and IgM antibodies in the sera of implanted mice with allogeneic ovarian tissue encapsulated in TheraCyte indicate that the implants did not evoke an allo-immune response, while the allogeneic controls were rejected 21 days after implantation. Our results show that TheraCyte effectively isolates the graft from immune recognition but also supports follicular growth.

Prognostic significance of highly sulfated chondroitin sulfates in ovarian cancer defined by the single chain antibody GD3A11.

PubMed

van der Steen, Sophieke C H A; van Tilborg, Angela A G; Vallen, Myrtille J E; Bulten, Johan; van Kuppevelt, Toin H; Massuger, Leon F A G

2016-03-01

The extracellular matrix (ECM) of ovarian cancer may provide a number of potential biomarkers. Chondroitin sulfate (CS), a class of sulfated polysaccharides, is abundantly present in the ECM of ovarian cancer. Structural alterations of CS chains (i.e. sulfation pattern) have been demonstrated to play a role in cancer development and progression. In this study we investigate the potential of highly sulfated CS as a biomarker in ovarian cancer using the single chain antibody GD3A11 selected by the phage display technology. The specificity of the antibody was determined by an indirect ELISA. GD3A11 epitope expression was assessed by immunohistochemistry in healthy organs, benign and malignant ovarian tumors (N=359) and correlated to clinical parameters. The CHST15 gene, responsible for the biosynthesis of highly sulfated CS was evaluated for mutation and methylation status. The GD3A11 epitope was minimally expressed in normal organs. Intense expression was observed in the ECM of different ovarian cancer subtypes, in contrast to benign ovarian tumors. Expression was independent of tumor grade, FIGO stage, and the use chemotherapy. For the aggressive ovarian cancer phenotype, intense expression was identified as an independent predictor for poor prognosis. CHST15 gene analysis showed no mutations nor an altered methylation status. Specific highly sulfated CS motifs expressed in the tumoral ECM hold biomarker potential in ovarian cancer patients. These matrix motifs constitute a novel class of biomarkers with prognostic significance and may be instrumental for innovative diagnostic and therapeutic applications (e.g. targeted therapy) in management of ovarian cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Dysregulated Estrogen Receptor Signaling in the Hypothalamic-Pituitary-Ovarian Axis Leads to Ovarian Epithelial Tumorigenesis in Mice

PubMed Central

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

2014-01-01

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. PMID:24603706

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

PubMed

Carter, Rebecca R; DiFeo, Analisa; Bogie, Kath; Zhang, Guo-Qiang; Sun, Jiayang

2014-01-01

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

An automated technique for potential differentiation of ovarian mature teratomas from other benign tumours using neural networks classification of 2D ultrasound static images: a pilot study

NASA Astrophysics Data System (ADS)

Al-karawi, Dhurgham; Sayasneh, A.; Al-Assam, Hisham; Jassim, Sabah; Page, N.; Timmerman, D.; Bourne, T.; Du, Hongbo

2017-05-01

Ovarian cysts are a common pathology in women of all age groups. It is estimated that 5-10% of women have a surgical intervention to remove an ovarian cyst in their lifetime. Given this frequency rate, characterization of ovarian masses is essential for optimal management of patients. Patients with benign ovarian masses can be managed conservatively if they are asymptomatic. Mature teratomas are common benign ovarian cysts that occur, in most cases, in premenopausal women. These ovarian cysts can contain different types of human tissue including bone, cartilage, fat, hair, or other tissue. If they are causing no symptoms, they can be harmless and may not require surgery. Subjective assessment by ultrasound examiners has a high diagnostic accuracy when characterising mature teratomas from other types of tumours. The aim of this study is to develop a computerised technique with the potential to characterise mature teratomas and distinguish them from other types of benign ovarian tumours. Local Binary Pattern (LBP) was applied to extract texture features that are specific in distinguishing teratomas. Neural Networks (NN) was then used as a classifier for recognising mature teratomas. A pilot sample set of 130 B-mode static ovarian ultrasound images (41 mature teratomas tumours and 89 other types of benign tumours) was used to test the effectiveness of the proposed technique. Test results show an average accuracy rate of 99.4% with a sensitivity of 100%, specificity of 98.8% and positive predictive value of 98.9%. This study demonstrates that the NN and LBP techniques can accurately classify static 2D B-mode ultrasound images of benign ovarian masses into mature teratomas and other types of benign tumours.

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

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.

Cryopreservation of ovarian tissue for fertility preservation in young female oncological patients.

PubMed

Andersen, Claus Yding; Kristensen, Stine Gry; Greve, Tine; Schmidt, Kirsten Tryde

2012-05-01

Girls and women suffering from a cancer that requires treatment with gonadotoxic drugs may experience cessation of reproductive function as a side effect due to obliteration of the ovarian pool of follicles. Techniques are now available for fertility preservation, such as cryopreservation of mature oocytes, embryos or ovarian cortical tissue. Whereas collection of mature oocytes and embryos requires at least a 2-week period, ovarian tissue may on short notice be frozen prior to treatment and can be transplanted back into women with ovarian failure. Transplanted frozen/thawed tissue supports survival and growth of follicles, giving rise to menstrual cycles and hormone production for several years. Worldwide, the procedure has resulted in the birth of 15 healthy children. Many cancer patients including girls and young women want fertility preservation, and the techniques are now being further developed and implemented in several centers.

The Ovary Is an Alternative Site of Origin for High-Grade Serous Ovarian Cancer in Mice

PubMed Central

Coffey, Donna M.; Ma, Lang; Matzuk, Martin M.

2015-01-01

Although named “ovarian cancer,” it has been unclear whether the cancer actually arises from the ovary, especially for high-grade serous carcinoma (HGSC), also known as high-grade serous ovarian cancer, the most common and deadliest ovarian cancer. In addition, the tumor suppressor p53 is the most frequently mutated gene in HGSC. However, whether mutated p53 can cause HGSC remains unknown. In this study, we bred a p53 mutation, p53R172H, into conditional Dicer-Pten double-knockout (DKO) mice, a mouse model duplicating human HGSC, to generate triple-mutant (TKO) mice. Like DKO mice, these TKO mice develop metastatic HGSCs originating from the fallopian tube. Unlike DKO mice, however, even after fallopian tubes are removed in TKO mice, ovaries alone can develop metastatic HGSCs, indicating that a p53 mutation can drive HGSC arising from the ovary. To confirm this, we generated p53R172H-Pten double-mutant mice, one of the genetic control lines for TKO mice. As anticipated, these double-mutant mice also develop metastatic HGSCs from the ovary, verifying the HGSC-forming ability of ovaries with a p53 mutation. Our study therefore shows that ovaries harboring a p53 mutation, as well as fallopian tubes, can be a distinct tissue source of high-grade serous ovarian cancer in mice. PMID:25815421

The ovary is an alternative site of origin for high-grade serous ovarian cancer in mice.

PubMed

Kim, Jaeyeon; Coffey, Donna M; Ma, Lang; Matzuk, Martin M

2015-06-01

Although named "ovarian cancer," it has been unclear whether the cancer actually arises from the ovary, especially for high-grade serous carcinoma (HGSC), also known as high-grade serous ovarian cancer, the most common and deadliest ovarian cancer. In addition, the tumor suppressor p53 is the most frequently mutated gene in HGSC. However, whether mutated p53 can cause HGSC remains unknown. In this study, we bred a p53 mutation, p53(R172H), into conditional Dicer-Pten double-knockout (DKO) mice, a mouse model duplicating human HGSC, to generate triple-mutant (TKO) mice. Like DKO mice, these TKO mice develop metastatic HGSCs originating from the fallopian tube. Unlike DKO mice, however, even after fallopian tubes are removed in TKO mice, ovaries alone can develop metastatic HGSCs, indicating that a p53 mutation can drive HGSC arising from the ovary. To confirm this, we generated p53(R172H)-Pten double-mutant mice, one of the genetic control lines for TKO mice. As anticipated, these double-mutant mice also develop metastatic HGSCs from the ovary, verifying the HGSC-forming ability of ovaries with a p53 mutation. Our study therefore shows that ovaries harboring a p53 mutation, as well as fallopian tubes, can be a distinct tissue source of high-grade serous ovarian cancer in mice.

The incidence and mortality of ovarian cancer and their relationship with the Human Development Index in Asia

PubMed Central

Razi, Saeid; Ghoncheh, Mahshid; Mohammadian-Hafshejani, Abdollah; Aziznejhad, Hojjat; Mohammadian, Mahdi; Salehiniya, Hamid

2016-01-01

Background The incidence and mortality estimates of ovarian cancer based on human development are essential for planning by policy makers. This study is aimed at investigating the standardised incidence rates (SIR) and standardised mortality rates (SMR) of ovarian cancer and their relationship with the Human Development Index (HDI) in Asian countries. Methods This study was an ecologic study in Asia for assessment of the correlation between SIR, age standardised rates (ASR), and HDI and their details, including life expectancy at birth, mean years of schooling, and gross national income (GNI) per capita. We used the correlation bivariate method for assessment of the correlation between ASR and HDI, and its details. Statistical significance was assumed if P < 0.05. All reported P-values were two-sided. Statistical analyses were performed using SPSS (Version 15.0, SPSS Inc.). Results The highest SIR of ovarian cancer was observed in Singapore, Kazakhstan, and Brunei respectively. Indonesia, Brunei, and Afghanistan had the highest SMR. There was a positive correlation between the HDI and SIR (r = 0.143, p = 0.006). Correlation between SMR of ovarian cancer and HDI was not significant (r = 0.005, p = 052.0). Conclusion According to the findings of this study, between the HDI and SIR, there was a positive correlation, but there was no correlation between the SMR and HDI. PMID:27110284

The incidence and mortality of ovarian cancer and their relationship with the Human Development Index in Asia.

PubMed

Razi, Saeid; Ghoncheh, Mahshid; Mohammadian-Hafshejani, Abdollah; Aziznejhad, Hojjat; Mohammadian, Mahdi; Salehiniya, Hamid

2016-01-01

The incidence and mortality estimates of ovarian cancer based on human development are essential for planning by policy makers. This study is aimed at investigating the standardised incidence rates (SIR) and standardised mortality rates (SMR) of ovarian cancer and their relationship with the Human Development Index (HDI) in Asian countries. This study was an ecologic study in Asia for assessment of the correlation between SIR, age standardised rates (ASR), and HDI and their details, including life expectancy at birth, mean years of schooling, and gross national income (GNI) per capita. We used the correlation bivariate method for assessment of the correlation between ASR and HDI, and its details. Statistical significance was assumed if P < 0.05. All reported P-values were two-sided. Statistical analyses were performed using SPSS (Version 15.0, SPSS Inc.). The highest SIR of ovarian cancer was observed in Singapore, Kazakhstan, and Brunei respectively. Indonesia, Brunei, and Afghanistan had the highest SMR. There was a positive correlation between the HDI and SIR (r = 0.143, p = 0.006). Correlation between SMR of ovarian cancer and HDI was not significant (r = 0.005, p = 052.0). According to the findings of this study, between the HDI and SIR, there was a positive correlation, but there was no correlation between the SMR and HDI.

[Central retinal vein occlusion as the first symptom of ovarian cancer].

PubMed

Asensio-Sánchez, V M; Hernaez-Ortega, M C; Castresana-Jauregui, I

2013-12-01

A healthy 57-year-old woman presented with decreased vision in her right eye. Dilated fundus examination revealed central retinal vein occlusion (CRVO). The laboratory test results for hypercoagulability state showed an abnormal protein S. A few months later she developed an ovarian malignancy. This case illustrates an association between CRVO and ovarian tumour. Coagulation disorders in cancer may be a mechanism for CRVO. Copyright © 2011 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

Prevention and management of ovarian hyperstimulation syndrome.

PubMed

Nelson, Scott M

2017-03-01

Ovarian hyperstimulation syndrome (OHSS) is a serious iatrogenic complication of ovarian stimulation. It is feasible to identify patients at risk, modify stimulation strategies to ameliorate risk, and initiate out-patient treatments that alter disease pathophysiology to reduce disease severity. Mitigation of OHSS risk and severity, through innovative approaches prior to treatment, during treatment and after treatment should now be standard care. This review summarizes recent developments and provides recommendations on the prevention and treatment of OHSS. © 2017 Elsevier Ltd. All rights reserved.

The role of cryopreservation for women prior to treatment of malignancy.

PubMed

Donnez, Jacques; Dolmans, Marie-Madeleine; Martinez-Madrid, Belen; Demylle, Dominique; Van Langendonckt, Anne

2005-08-01

The purpose of this review is to investigate recent advances in xenografting, as well as in orthotopic and heterotopic autotransplantation of human cryopreserved ovarian tissue. The first livebirth after orthotopic transplantation of cryopreserved ovarian tissue was reported recently. We discuss this case and other cases of reimplantation of cryopreserved ovarian tissue, bearing in mind that many questions remain. Finally, we report the latest developments in research on the transplantation of an intact ovary and the reimplantation of isolated follicles.

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

PubMed Central

Ramsey, Mary; Crews, David

2009-01-01

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

Molecular Characterization of Epithelial Ovarian Cancer: Implications for Diagnosis and Treatment.

PubMed

Rojas, Veronica; Hirshfield, Kim M; Ganesan, Shridar; Rodriguez-Rodriguez, Lorna

2016-12-15

Epithelial ovarian cancer is a highly heterogeneous disease characterized by multiple histological subtypes. Molecular diversity has been shown to occur within specific histological subtypes of epithelial ovarian cancer, between different tumors of an individual patient, as well as within individual tumors. Recent advances in the molecular characterization of epithelial ovarian cancer tumors have provided the basis for a simplified classification scheme in which these cancers are classified as either type I or type II tumors, and these two categories have implications regarding disease pathogenesis and prognosis. Molecular analyses, primarily based on next-generation sequencing, otherwise known as high-throughput sequencing, are allowing for further refinement of ovarian cancer classification, facilitating the elucidation of the site(s) of precursor lesions of high-grade serous ovarian cancer, and providing insight into the processes of clonal selection and evolution that may be associated with development of chemoresistance. Potential therapeutic targets have been identified from recent molecular profiling studies of these tumors, and the effectiveness and safety of a number of specific targeted therapies have been evaluated or are currently being studied for the treatment of women with this disease.

Molecular Characterization of Epithelial Ovarian Cancer: Implications for Diagnosis and Treatment

PubMed Central

Rojas, Veronica; Hirshfield, Kim M.; Ganesan, Shridar; Rodriguez-Rodriguez, Lorna

2016-01-01

Epithelial ovarian cancer is a highly heterogeneous disease characterized by multiple histological subtypes. Molecular diversity has been shown to occur within specific histological subtypes of epithelial ovarian cancer, between different tumors of an individual patient, as well as within individual tumors. Recent advances in the molecular characterization of epithelial ovarian cancer tumors have provided the basis for a simplified classification scheme in which these cancers are classified as either type I or type II tumors, and these two categories have implications regarding disease pathogenesis and prognosis. Molecular analyses, primarily based on next-generation sequencing, otherwise known as high-throughput sequencing, are allowing for further refinement of ovarian cancer classification, facilitating the elucidation of the site(s) of precursor lesions of high-grade serous ovarian cancer, and providing insight into the processes of clonal selection and evolution that may be associated with development of chemoresistance. Potential therapeutic targets have been identified from recent molecular profiling studies of these tumors, and the effectiveness and safety of a number of specific targeted therapies have been evaluated or are currently being studied for the treatment of women with this disease. PMID:27983698

Characterizing optical properties and spatial heterogeneity of human ovarian tissue using spatial frequency domain imaging

NASA Astrophysics Data System (ADS)

Nandy, Sreyankar; Mostafa, Atahar; Kumavor, Patrick D.; Sanders, Melinda; Brewer, Molly; Zhu, Quing

2016-10-01

A spatial frequency domain imaging (SFDI) system was developed for characterizing ex vivo human ovarian tissue using wide-field absorption and scattering properties and their spatial heterogeneities. Based on the observed differences between absorption and scattering images of different ovarian tissue groups, six parameters were quantitatively extracted. These are the mean absorption and scattering, spatial heterogeneities of both absorption and scattering maps measured by a standard deviation, and a fitting error of a Gaussian model fitted to normalized mean Radon transform of the absorption and scattering maps. A logistic regression model was used for classification of malignant and normal ovarian tissues. A sensitivity of 95%, specificity of 100%, and area under the curve of 0.98 were obtained using six parameters extracted from the SFDI images. The preliminary results demonstrate the diagnostic potential of the SFDI method for quantitative characterization of wide-field optical properties and the spatial distribution heterogeneity of human ovarian tissue. SFDI could be an extremely robust and valuable tool for evaluation of the ovary and detection of neoplastic changes of ovarian cancer.

MiR-212 exerts suppressive effect on SKOV3 ovarian cancer cells through targeting HBEGF.

PubMed

Wei, Li-Qiang; Liang, Hui-Tao; Qin, Dong-Chun; Jin, Hui-Fang; Zhao, Yong; She, Ming-Cong

2014-12-01

MicroRNAs (miRNAs) play critical roles in the development and progression of ovarian cancer. We found that miR-212 was significantly downregulated in serum and tissues from epithelial ovarian cancer (EOC) patients. Overexpression of miR-212 in ovarian cancer cells inhibited cell proliferation, migration, and invasion. Luciferase reporter assay confirmed HBEGF as a direct target of miR-212. Overexpression of miR-212 decreased HBEGF expression at both the protein and messenger RNA (mRNA) levels. Knockdown of HBEGF expression in SKOV3 cell line significantly inhibited cell growth, migration, and invasion. HBEGF mRNA level was upregulated in EOC tissues and inversely correlated with miR-212 expression in tissues. Upregulation of HBEGF could attenuate the effect induced by miR-212. These findings indicate that miR-212 displays a tumor-suppressive effect in human ovarian cancer. And miR-212 suppresses cell proliferation, migration, and invasion by targeting the HBEGF transcript, highlighting the therapeutic potential of miR-212 and HBEGF in epithelial ovarian cancer treatment.

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

ClinicalTrials.gov

2018-06-20

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

Comparison of In Vitro- and Chorioallantoic Membrane (CAM)-Culture Systems for Cryopreserved Medulla-Contained Human Ovarian Tissue

PubMed Central

Isachenko, Vladimir; Mallmann, Peter; Petrunkina, Anna M.; Rahimi, Gohar; Nawroth, Frank; Hancke, Katharina; Felberbaum, Ricardo; Genze, Felicitas; Damjanoski, Ilija; Isachenko, Evgenia

2012-01-01

At present, there are three ways to determine effectively the quality of the cryopreservation procedure using ovarian tissue before the re-implantation treatment: evaluation of follicles after post-thawing xenotransplantation to SCID mouse, in-vitro culture in a large volume of culture medium under constant agitation and culture on embryonic chorio-allantoic membrane within a hen's eggs. The aim of this study was to compare the two methods, culture in vitro and culture on embryonic chorioallantoic membrane (CAM) of cryopreserved human ovarian medulla-contained and medulla-free cortex. Ovarian fragments were divided into small pieces (1.5–2.0×1.0–1.2×0.8–1.5) of two types, cortex with medulla and medulla-free cortex, frozen, thawed and randomly divided into the following four groups. Group 1: medulla-free cortex cultured in vitro for 8 days in large volume of medium with mechanical agitation, Group 2: medulla-containing cortex cultured in vitro, Group 3: medulla-free cortex cultured in CAM-system for 5 days, Group 4: medulla-containing cortex cultured in CAM-system. The efficacy of the tissue culture was evaluated by the development of follicles and by intensiveness of angiogenesis in the tissue (von Willebrand factor and Desmin). For Group 1, 2, 3 and 4, respectively 85%, 85%, 87% and 84% of the follicles were morphologically normal (P>0.1). The immunohistochemical analysis showed that angiogenesis detected by von Willebrand factor was lower in groups 1 and 3 (medulla-free cortex). Neo-vascularisation (by Desmin) was observed only in ovarian tissue of Group 4 (medulla-contained cortex after CAM-culture). It appears that the presence of medulla in ovarian pieces is beneficial for post-thaw development of cryopreserved human ovarian tissue. For medical practice it is recommended for evaluation of post-warming ovarian tissue to use the CAM-system as a valuable alternative to xenotransplantation and for cryopreservation of these tissues to prepare ovarian medulla-contained strips. PMID:22479331

Development and Preliminary Evaluation of a Multivariate Index Assay for Ovarian Cancer

PubMed Central

Chen, Tzong-Hao; Bergstrom, Katharine J.; Zhao, Jinghua; Seshaiah, Partha; Yip, Ping; Mansfield, Brian C.

2009-01-01

Background Most women with a clinical presentation consistent with ovarian cancer have benign conditions. Therefore methods to distinguish women with ovarian cancer from those with benign conditions would be beneficial. We describe the development and preliminary evaluation of a serum-based multivariate assay for ovarian cancer. This hypothesis-driven study examined whether an informative pattern could be detected in stage I disease that persists through later stages. Methodology/Principal Findings Sera, collected under uniform protocols from multiple institutions, representing 176 cases and 187 controls from women presenting for surgery were examined using high-throughput, multiplexed immunoassays. All stages and common subtypes of epithelial ovarian cancer, and the most common benign ovarian conditions were represented. A panel of 104 antigens, 44 autoimmune and 56 infectious disease markers were assayed and informative combinations identified. Using a training set of 91 stage I data sets, representing 61 individual samples, and an equivalent number of controls, an 11-analyte profile, composed of CA-125, CA 19-9, EGF-R, C-reactive protein, myoglobin, apolipoprotein A1, apolipoprotein CIII, MIP-1α, IL-6, IL-18 and tenascin C was identified and appears informative for all stages and common subtypes of ovarian cancer. Using a testing set of 245 samples, approximately twice the size of the model building set, the classifier had 91.3% sensitivity and 88.5% specificity. While these preliminary results are promising, further refinement and extensive validation of the classifier in a clinical trial is necessary to determine if the test has clinical value. Conclusions/Significance We describe a blood-based assay using 11 analytes that can distinguish women with ovarian cancer from those with benign conditions. Preliminary evaluation of the classifier suggests it has the potential to offer approximately 90% sensitivity and 90% specificity. While promising, the performance needs to be assessed in a blinded clinical validation study. PMID:19240799

An Embryonic and Induced Pluripotent Stem Cell Model for Ovarian Granulosa Cell Development and Steroidogenesis.

PubMed

Lipskind, Shane; Lindsey, Jennifer S; Gerami-Naini, Behzad; Eaton, Jennifer L; O'Connell, Daniel; Kiezun, Adam; Ho, Joshua W K; Ng, Nicholas; Parasar, Parveen; Ng, Michelle; Nickerson, Michael; Demirci, Utkan; Maas, Richard; Anchan, Raymond M

2018-05-01

Embryoid bodies (EBs) can serve as a system for evaluating pluripotency, cellular differentiation, and tissue morphogenesis. In this study, we use EBs derived from mouse embryonic stem cells (mESCs) and human amniocyte-derived induced pluripotent stem cells (hAdiPSCs) as a model for ovarian granulosa cell (GC) development and steroidogenic cell commitment. We demonstrated that spontaneously differentiated murine EBs (mEBs) and human EBs (hEBs) displayed ovarian GC markers, such as aromatase (CYP19A1), FOXL2, AMHR2, FSHR, and GJA1. Comparative microarray analysis identified both shared and unique gene expression between mEBs and the maturing mouse ovary. Gene sets related to gonadogenesis, lipid metabolism, and ovarian development were significantly overrepresented in EBs. Of the 29 genes, 15 that were differentially regulated in steroidogenic mEBs displayed temporal expression changes between embryonic, postnatal, and mature ovarian tissues by polymerase chain reaction. Importantly, both mEBs and hEBs were capable of gonadotropin-responsive estradiol (E2) synthesis in vitro (217-759 pg/mL). Live fluorescence-activated cell sorting-sorted AMHR2 + granulosa-like cells from mEBs continued to produce E2 after purification (15.3 pg/mL) and secreted significantly more E2 than AMHR2 - cells (8.6 pg/mL, P < .05). We conclude that spontaneously differentiated EBs of both mESC and hAdiPSC origin can serve as a biologically relevant model for ovarian GC differentiation and steroidogenic cell commitment. These cells should be further investigated for therapeutic uses, such as stem cell-based hormone replacement therapy and in vitro maturation of oocytes.

Efficacy of neratinib in the treatment of HER2/neu-amplified epithelial ovarian carcinoma in vitro and in vivo.

PubMed

Menderes, Gulden; Bonazzoli, Elena; Bellone, Stefania; Black, Jonathan D; Lopez, Salvatore; Pettinella, Francesca; Masserdotti, Alice; Zammataro, Luca; Litkouhi, Babak; Ratner, Elena; Silasi, Dan-Arin; Azodi, Masoud; Schwartz, Peter E; Santin, Alessandro D

2017-05-01

Epithelial ovarian carcinoma is the most lethal of gynecologic malignancies. There is a need to optimize the currently available treatment strategies and to urgently develop novel therapeutic agents against chemotherapy-resistant disease. The objective of our study was to evaluate neratinib's preclinical efficacy in treating HER2-amplified ovarian cancer. Neratinib's efficacy in treating HER2-amplified ovarian cancer was studied in vitro utilizing six primary tumor cell lines with differential HER2/neu expression. Flow cytometry was utilized to assess IC 50 , cell signaling changes, and cell cycle distribution. Neratinib's in vivo efficacy was evaluated in HER2-amplified epithelial ovarian carcinoma xenografts. Three of six (50%) ovarian cancer cell lines were HER2/neu-amplified. Neratinib showed significantly higher efficacy in treating HER2/neu-amplified cell lines when compared to the non-HER2/neu-amplified tumor cell lines (mean ± SEM IC 50 :0.010 μM ± 0.0003 vs. 0.076 μM ± 0.005 p < 0.0001). Neratinib treatment significantly decreased the phosphorylation of the transcription factor S6, leading to arrest of the cell cycle in G0/G1 phase. Neratinib prolonged survival in mice harboring HER2-amplified epithelial ovarian carcinoma xenografts (p = 0.003). Neratinib inhibits proliferation, signaling, cell cycle progression and tumor growth of HER2-amplified epithelial ovarian carcinoma in vitro. Neratinib inhibits xenograft growth and improves overall survival in HER2/neu-amplified ovarian cancer in vivo. Clinical trials are warranted.

Efficacy of neratinib in the treatment of HER2/neu-amplified epithelial ovarian carcinoma in vitro and in vivo

PubMed Central

Menderes, Gulden; Bonazzoli, Elena; Bellone, Stefania; Black, Jonathan D.; Lopez, Salvatore; Pettinella, Francesca; Masserdotti, Alice; Zammataro, Luca; Litkouhi, Babak; Ratner, Elena; Silasi, Dan-Arin; Azodi, Masoud; Schwartz, Peter E.

2018-01-01

Epithelial ovarian carcinoma is the most lethal of gynecologic malignancies. There is a need to optimize the currently available treatment strategies and to urgently develop novel therapeutic agents against chemotherapy-resistant disease. The objective of our study was to evaluate neratinib’s preclinical efficacy in treating HER2-amplified ovarian cancer. Neratinib’s efficacy in treating HER2-amplified ovarian cancer was studied in vitro utilizing six primary tumor cell lines with differential HER2/neu expression. Flow cytometry was utilized to assess IC50, cell signaling changes, and cell cycle distribution. Neratinib’s in vivo efficacy was evaluated in HER2-amplified epithelial ovarian carcinoma xenografts. Three of six (50%) ovarian cancer cell lines were HER2/neu-amplified. Neratinib showed significantly higher efficacy in treating HER2/neu-amplified cell lines when compared to the non-HER2/neu-amplified tumor cell lines (mean ± SEM IC50:0.010 μM ± 0.0003 vs. 0.076 μM ± 0.005 p < 0.0001). Neratinib treatment significantly decreased the phosphorylation of the transcription factor S6, leading to arrest of the cell cycle in G0/G1 phase. Neratinib prolonged survival in mice harboring HER2-amplified epithelial ovarian carcinoma xenografts (p = 0.003). Neratinib inhibits proliferation, signaling, cell cycle progression and tumor growth of HER2-amplified epithelial ovarian carcinoma in vitro. Neratinib inhibits xenograft growth and improves overall survival in HER2/neu-amplified ovarian cancer in vivo. Clinical trials are warranted. PMID:28397106

Targeting Serous Epithelial Ovarian Cancer with Designer Zinc Finger Transcription Factors*

PubMed Central

Lara, Haydee; Wang, Yuhua; Beltran, Adriana S.; Juárez-Moreno, Karla; Yuan, Xinni; Kato, Sumie; Leisewitz, Andrea V.; Cuello Fredes, Mauricio; Licea, Alexei F.; Connolly, Denise C.; Huang, Leaf; Blancafort, Pilar

2012-01-01

Ovarian cancer is the leading cause of death among gynecological malignancies. It is detected at late stages when the disease is spread through the abdominal cavity in a condition known as peritoneal carcinomatosis. Thus, there is an urgent need to develop novel therapeutic interventions to target advanced stages of ovarian cancer. Mammary serine protease inhibitor (Maspin) represents an important metastasis suppressor initially identified in breast cancer. Herein we have generated a sequence-specific zinc finger artificial transcription factor (ATF) to up-regulate the Maspin promoter in aggressive ovarian cancer cell lines and to interrogate the therapeutic potential of Maspin in ovarian cancer. We found that although Maspin was expressed in some primary ovarian tumors, the promoter was epigenetically silenced in cell lines derived from ascites. Transduction of the ATF in MOVCAR 5009 cells derived from ascitic cultures of a TgMISIIR-TAg mouse model of ovarian cancer resulted in tumor cell growth inhibition, impaired cell invasion, and severe disruption of actin cytoskeleton. Systemic delivery of lipid-protamine-RNA nanoparticles encapsulating a chemically modified ATF mRNA resulted in inhibition of ovarian cancer cell growth in nude mice accompanied with Maspin re-expression in the treated tumors. Gene expression microarrays of ATF-transduced cells revealed an exceptional specificity for the Maspin promoter. These analyses identified novel targets co-regulated with Maspin in human short-term cultures derived from ascites, such as TSPAN12, that could mediate the anti-metastatic phenotype of the ATF. Our work outlined the first targeted, non-viral delivery of ATFs into tumors with potential clinical applications for metastatic ovarian cancers. PMID:22782891

Ovarian carcinoma in a 14-year-old with classical salt-wasting congenital adrenal hyperplasia and bilateral adrenalectomy.

PubMed

Pina, Christian; Khattab, Ahmed; Katzman, Philip; Bruckner, Lauren; Andolina, Jeffrey; New, Maria; Yau, Mabel

2015-05-01

A 14-year-old female with classical congenital adrenal hyperplasia because of 21-hydroxylase deficiency underwent bilateral adrenalectomy at 6 years of age as a result of poor hormonal control. Because the patient was adrenalectomized, extra adrenal androgen production was suspected. Imaging studies including pelvic ultrasound and pelvic magnetic resonance imaging (MRI) were obtained to evaluate for adrenal rest tumors of the ovaries. Abdominal MRI was obtained to evaluate for residual adrenal tissue. A cystic lesion arising from her right ovary suspicious for ovarian neoplasm was noted on pelvic MRI. Right salpingo-oophorectomy was performed and histopathological examination revealed ovarian serous adenocarcinoma, low-grade, and well-differentiated. Tumor marker CA-125 was elevated and additional ovarian cancer staging workup confirmed stage IIIC due to one lymph node positive for carcinoma. The patient then developed a large left ovarian cyst, which led to a complete total abdominal hysterectomy and removal of the left ovary and fallopian tube. Pathology confirmed ovarian serous adenocarcinoma with microscopic focus of carcinoma in the left ovary. After numerous complications, the patient responded well to chemotherapy, CA-125 levels fell and no evidence of carcinoma was observed on subsequent imaging. To our knowledge, this is the first reported case of an ovarian serous adenocarcinoma in a patient with CAH. Although rare, we propose that the ovaries were the origin of androgen production and not residual adrenal tissue. The relationship between CAH and ovarian carcinomas has yet to be established, but further evaluation is needed given the poor survival rate of high-grade serous ovarian carcinoma.

[The molecular biology of epithelial ovarian cancer].

PubMed

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

2012-12-01

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

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

PubMed

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

2016-08-01

Ovarian cancer is commonly treated with cisplatin and paclitaxel combination chemotherapy; however, ovarian cancer cells often develop resistance to these drugs. Increasingly, microRNAs (miRNAs) including miR-873 have been implicated in drug resistance in many cancers, but the role of miR-873 in ovarian cancer remains unknown. MTT cell viability assays revealed that the sensitivities of ovarian cancer lines to cisplatin and paclitaxel increased following transfection with miR-873 (P < 0.05). After predicting the miR-873 binding region in the 3'-untranslated region of ABCB1, dual-luciferase reporter assay confirmed this prediction. RT-PCR and Western blotting revealed that MDR1 expression was significantly downregulated after transfection with miR-873 and upregulated after transfection with anti-miR-873 at both mRNA and protein levels compared to negative controls (P < 0.05). Experiments in a mouse xenograft model confirmed that intratumoral administration of miR-873 could enhance the efficacy of cisplatin in inhibiting tumor growth in ovarian cancer in vivo (P < 0.05). ABCB1 overexpression reduced sensitivities of ovarian cancer lines OVCAR3 and A2780 to cisplatin and paclitaxel, which can be reversed by miR-873 mimic transfection (P < 0.05). In summary, we demonstrated that overexpression of miR-873 increased the sensitivity of ovarian cancer cells to cisplatin and paclitaxel by targeting MDR1 expression. Our findings suggest that combination therapies with chemotherapy agents and miR-873 may suppress drug resistance in ovarian cancer.

Role of vitamin D in ovarian physiology and its implication in reproduction: a systematic review.

PubMed

Irani, Mohamad; Merhi, Zaher

2014-08-01

To report an update on the role of vitamin D (VD) in ovarian physiology with a focus on genes involved in steroidogenesis, follicular development, and ovarian reserve, as well as ovulatory dysfunction associated with polycystic ovary syndrome (PCOS), and ovarian response to assisted reproductive technology (ART). Systematic review. Not applicable. Human, animal, and cell culture models. Pubmed literature search. Granulosa cell function, serum antimüllerian hormone (AMH), AMH and its receptor gene expression, soluble receptor for advanced glycation end-products (sRAGE), PCOS parameters, and ART outcome. In human granulosa cells, VD alters AMH signaling, FSH sensitivity, and progesterone production and release, indicating a possible physiologic role for VD in ovarian follicular development and luteinization. In the serum, 25-hydroxyvitamin D (25OH-D) is positively correlated with AMH, and appropriate VD supplementation in VD-depleted women can suppress the seasonal changes that occur in serum AMH. In VD-deficient women with PCOS, VD supplementation lowers the abnormally elevated serum AMH levels, possibly indicating a mechanism by which VD improves folliculogenesis. The antiinflammatory sRAGE serum levels significantly increase in women with PCOS after VD replacement. Although follicular fluid 25OH-D correlates with IVF outcomes, there is a lack of data pertaining to the impact of VD supplementation on pregnancy rates following IVF. This review underscores the need for understanding the mechanistic actions of VD in ovarian physiology and the critical need for randomized trials to elucidate the impact of VD supplementation on controlled ovarian hyperstimulation/IVF outcome and ovulatory dysfunction associated with PCOS. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2015-07-01

Tumor-associated neoangiogenesis (TAN) is an early event in ovarian cancer (OVCA) development. Increased expression of vascular endothelial growth factor receptor 2 (VEGFR2) by TAN vessels presents a potential target for early detection by ultrasound imaging. The goal of this study was to examine the suitability of VEGFR2-targeted ultrasound contrast agents in detecting spontaneous OVCA in laying hens. Effects of VEGFR2-targeted contrast agents in enhancing the intensity of ultrasound imaging from spontaneous ovarian tumors in hens were examined in a cross-sectional study. Enhancement in the intensity of ultrasound imaging was determined before and after injection of VEGFR2-targeted contrast agents. All ultrasound images were digitally stored and analyzed off-line. Following scanning, ovarian tissues were collected and processed for histology and detection of VEGFR2-expressing microvessels. Enhancement in visualization of ovarian morphology was detected by gray-scale imaging following injection of VEGFR2-targeted contrast agents. Compared with pre-contrast, contrast imaging enhanced the intensities of ultrasound imaging significantly (p < 0.0001) irrespective of the pathological status of ovaries. In contrast to normal hens, the intensity of ultrasound imaging was significantly (p < 0.0001) higher in hens with early stage OVCA and increased further in hens with late stage OVCA. Higher intensities of ultrasound imaging in hens with OVCA were positively correlated with increased (p < 0.0001) frequencies of VEGFR2-expressing microvessels. The results of this study suggest that VEGFR2-targeted contrast agents enhance the visualization of spontaneous ovarian tumors in hens at early and late stages of OVCA. The laying hen may be a suitable model to test new imaging agents and develop targeted therapeutics. © The Author(s) 2014.

New methods to improve the safety assessment of cryopreserved ovarian tissue for fertility preservation in breast cancer patients.

PubMed

Rodríguez-Iglesias, Beatriz; Novella-Maestre, Edurne; Herraiz, Sonia; Díaz-García, César; Pellicer, Nuria; Pellicer, Antonio

2015-12-01

To develop a novel molecular panel of markers to detect breast cancer (BC) disseminated malignant cells in ovarian tissue, and to improve the safety of ovarian tissue transplantation. Experimental study. University hospital. Ten ovarian biopsies from healthy patients, 13 biopsies with diagnosed BC metastasis, and 4 biopsies from primary BC tumor for designing a diagnostic panel of BC cell contamination; 60 ovarian biopsies from BC patients undergoing fertility preservation for validating the panel. Female nude mice. A novel panel for BC malignant cell detection by reverse-transcription polymerase chain reaction (RT-PCR), inmmunohistochemical analysis, in vitro invasion assay and xenotransplantation assayed in ovarian tissue from BC patients. Expression of GCDFP15, MGB1, SBEM, MUC1, WT-1, and NY-BR-01, selected as markers, assessed by quantitative RT-PCR in samples with confirmed BC metastasis. The most sensitive markers were confirmed by immunohistochemistry, and tested in vitro and in vivo. GCDFP15, MGB1, and SBEM were the most sensitive and specific markers to detect BC metastatic cells when at least one was expressed by quantitative RT-PCR. The panel was validated in 60 patients and confirmed in an in vitro invasion assay, where no invasive cells were observed. Samples negative for BC cells cannot develop disease when xenografted. GCDFP15, MGB1, and SBEM were the most sensitive molecules to create a diagnostic panel for BC malignant cell contamination, which may make ovarian tissue cryopreservation and transplantation a safe technique for fertility preservation in BC patients. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Growth Hormone Ameliorates the Radiotherapy-Induced Ovarian Follicular Loss in Rats: Impact on Oxidative Stress, Apoptosis and IGF-1/IGF-1R Axis

PubMed Central

Mahran, Yasmen F.; El-Demerdash, Ebtehal; Nada, Ahmed S.; El-Naga, Reem N.; Ali, Azza A.; Abdel-Naim, Ashraf B.

2015-01-01

Radiotherapy is one of the standard cytotoxic therapies for cancer. However, it has a profound impact on ovarian function leading to premature ovarian failure and infertility. Since none of the currently available methods for fertility preservation guarantees future fertility, the need for an effective radioprotective agent is highly intensified. The present study investigated the mechanisms of the potential radioprotective effect of growth hormone (GH) on γ irradiation-induced ovarian failure and the impact of the insulin like growth factor 1 (IGF-1) in the underlying protection. Immature female Sprague-Dawley rats were either exposed to single whole body irradiation (3.2 Gy) and/or treated with GH (1 mg/kg s.c). Experimental γ-irradiation produced an array of ovarian dysfunction that was evident by assessment of hormonal changes, follicular development, proliferation marker (PCNA), oxidative stress as well as apoptotic markers. In addition, IGF-1/IGF-1R axis expression was assessed using real-time PCR and immunolocalization techniques. Furthermore, after full maturity, fertility assessment was performed. GH significantly enhanced follicular development and restored anti-Mullerian hormone serum level as compared with the irradiated group. In addition, GH significantly ameliorated the deleterious effects of irradiation on oxidative status, PCNA and apoptosis. Interestingly, GH was shown to enhance the ovarian IGF-1 at transcription and translation levels, a property that contributes significantly to its radioprotective effect. Finally, GH regained the fertility that was lost following irradiation. In conclusion, GH showed a radioprotective effect and rescued the ovarian reserve through increasing local IGF-1 level and counteracting the oxidative stress-mediated apoptosis. PMID:26465611

Growth Hormone Ameliorates the Radiotherapy-Induced Ovarian Follicular Loss in Rats: Impact on Oxidative Stress, Apoptosis and IGF-1/IGF-1R Axis.

PubMed

Mahran, Yasmen F; El-Demerdash, Ebtehal; Nada, Ahmed S; El-Naga, Reem N; Ali, Azza A; Abdel-Naim, Ashraf B

2015-01-01

Radiotherapy is one of the standard cytotoxic therapies for cancer. However, it has a profound impact on ovarian function leading to premature ovarian failure and infertility. Since none of the currently available methods for fertility preservation guarantees future fertility, the need for an effective radioprotective agent is highly intensified. The present study investigated the mechanisms of the potential radioprotective effect of growth hormone (GH) on γ irradiation-induced ovarian failure and the impact of the insulin like growth factor 1 (IGF-1) in the underlying protection. Immature female Sprague-Dawley rats were either exposed to single whole body irradiation (3.2 Gy) and/or treated with GH (1 mg/kg s.c). Experimental γ-irradiation produced an array of ovarian dysfunction that was evident by assessment of hormonal changes, follicular development, proliferation marker (PCNA), oxidative stress as well as apoptotic markers. In addition, IGF-1/IGF-1R axis expression was assessed using real-time PCR and immunolocalization techniques. Furthermore, after full maturity, fertility assessment was performed. GH significantly enhanced follicular development and restored anti-Mullerian hormone serum level as compared with the irradiated group. In addition, GH significantly ameliorated the deleterious effects of irradiation on oxidative status, PCNA and apoptosis. Interestingly, GH was shown to enhance the ovarian IGF-1 at transcription and translation levels, a property that contributes significantly to its radioprotective effect. Finally, GH regained the fertility that was lost following irradiation. In conclusion, GH showed a radioprotective effect and rescued the ovarian reserve through increasing local IGF-1 level and counteracting the oxidative stress-mediated apoptosis.

Reproductive biology of the prawn Melicertus kerathurus (Decapoda: Penaeidae) in Thermaikos Gulf (N. Aegean Sea)

NASA Astrophysics Data System (ADS)

Kevrekidis, Kosmas; Thessalou-Legaki, Maria

2013-03-01

The reproductive biology including insemination frequency, ovarian maturation, gonadosomatic index (GSI), size at first maturity, and fecundity of Melicertus kerathurus were investigated using monthly samples from Thermaikos Gulf. Insemination was recorded by the presence of a spermatophore in the thelycum, and ovarian development was based on macroscopic ovarian staging (ST1-ST5). Inseminated females were found throughout the year with high percentages recorded from April to July. Although all ovarian stages were represented in mated females, insemination increased with size and ovarian maturation. High percentages of vitellogenic or mature ovarian stages were observed from May to July, while immature and developing ovaries were predominant mainly in winter. Spawned ovaries occurred from May to October. Carapace length at first maturity based on the presence of a spermatophore (CL50sp) was estimated at 39.20 mm, while that based on the presence of vitellogenic and mature ovaries (CL50ov) at 40.70 mm. The seasonal peak in the proportion of mature females (ST4) varied with size. Inseminated females at ST4 and GSI peaked in June-July. GSI varied in relation to insemination status and ovarian stage. In large females (>50 mm CL), the decline in mature ovaries and GSI increment with size indicates a relative reduction in the reproductive output. The number of oocytes ranged from 62,742 to 602,947 (mean ± SD: 268,000 ± 113,000). As the prawns are targeted during the spawning season, mainly by the artisanal fishery, and female size at first maturity is selected by artisanal net size, managerial measures toward artisanal fishery should be implemented.

RNA-based ovarian cancer research from 'a gene to systems biomedicine' perspective.

PubMed

Gov, Esra; Kori, Medi; Arga, Kazim Yalcin

2017-08-01

Ovarian cancer remains the leading cause of death from a gynecologic malignancy, and treatment of this disease is harder than any other type of female reproductive cancer. Improvements in the diagnosis and development of novel and effective treatment strategies for complex pathophysiologies, such as ovarian cancer, require a better understanding of disease emergence and mechanisms of progression through systems medicine approaches. RNA-level analyses generate new information that can help in understanding the mechanisms behind disease pathogenesis, to identify new biomarkers and therapeutic targets and in new drug discovery. Whole RNA sequencing and coding and non-coding RNA expression array datasets have shed light on the mechanisms underlying disease progression and have identified mRNAs, miRNAs, and lncRNAs involved in ovarian cancer progression. In addition, the results from these analyses indicate that various signalling pathways and biological processes are associated with ovarian cancer. Here, we present a comprehensive literature review on RNA-based ovarian cancer research and highlight the benefits of integrative approaches within the systems biomedicine concept for future ovarian cancer research. We invite the ovarian cancer and systems biomedicine research fields to join forces to achieve the interdisciplinary caliber and rigor required to find real-life solutions to common, devastating, and complex diseases such as ovarian cancer. CAF: cancer-associated fibroblasts; COG: Cluster of Orthologous Groups; DEA: disease enrichment analysis; EOC: epithelial ovarian carcinoma; ESCC: oesophageal squamous cell carcinoma; GSI: gamma secretase inhibitor; GO: Gene Ontology; GSEA: gene set enrichment analyzes; HAS: Hungarian Academy of Sciences; lncRNAs: long non-coding RNAs; MAPK/ERK: mitogen-activated protein kinase/extracellular signal-regulated kinases; NGS: next-generation sequencing; ncRNAs: non-coding RNAs; OvC: ovarian cancer; PI3K/Akt/mTOR: phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin; RT-PCR: real-time polymerase chain reaction; SNP: single nucleotide polymorphism; TF: transcription factor; TGF-β: transforming growth factor-β.

Effects of Per2 overexpression on growth inhibition and metastasis, and on MTA1, nm23-H1 and the autophagy-associated PI3K/PKB signaling pathway in nude mice xenograft models of ovarian cancer

PubMed Central

WANG, ZHAOXIA; LI, LI; WANG, YANG

2016-01-01

The aim of the present study was to evaluate the association between Period2 (Per2) and the occurrence and development of ovarian cancer, in addition to evaluating the effect of this gene on the growth and metastasis of ovarian cancer in nude mice xenograft models. The detection of Per2 by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting methods at various stages of ovarian cancer in tumor tissue samples was conducted. Nude mice xenograft models of ovarian cancer were constructed using an ovarian cancer cell line and, using a gene transfection technique, exogenous infusion of the recombinant gene, Per2, was performed. To assess for the successful and stable expression of Per2 in the tumor tissue, levels of Per2 expression in the nude mice xenograft models were detected by RT-qPCR. During the experimental period, the tumor volumes were measured every three days. Two weeks following treatment cessation, the nude mice were sacrificed and the tumor weight and volume were measured. Furthermore, detection of the changes in expression levels of metastasis-associated gene 1 (MTA-1) and tumor metastasis suppressor gene, non-metastasis protein 23-H1 (nm23-H1), and the expression change of autophagy-associated signal transduction pathway, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB) kinase were analyzed. The findings demonstrated that with ovarian cancer stage development, the expression of Per2 gradually reduced or ceased. In addition, exogenous Per2 was successfully and stably expressed in nude mice tumor tissue samples. Furthermore, in the Per2 overexpression group, MTA-1 protein expression was significantly reduced when compared with the phosphate-buffered saline (PBS) control and empty plasmid groups, while nm23-H1 protein expression was significantly higher when compared with those two groups. The expression levels of PI3K and PKB kinase, which are marker proteins of the autophagy associated signaling pathway PI3K/PKB, were significantly downregulated, when compared with the PBS control and empty plasmid groups (P<0.001). Thus, it was demonstrated that Per2 is closely associated with the development of ovarian cancer, and late-stage ovarian cancer is associated with Per2 mutation or deletion. Per2 overexpression, via exogenous infusion reduced the ovarian cancer growth rate, which was demonstrated by a significant increase in the tumor inhibition rate. In addition, Per2 may inhibit the expression of MTA-1 and promote the expression of nm23-H1 to restrict ovarian tumor growth and metastasis. Finally, it is hypothesized that Per2 affects autophagy by interfering with the PI3K/PKB signaling pathway, causing inhibition of tumor angiogenesis in order to inhibit tumor growth. PMID:27082164

Effects of Per2 overexpression on growth inhibition and metastasis, and on MTA1, nm23-H1 and the autophagy-associated PI3K/PKB signaling pathway in nude mice xenograft models of ovarian cancer.

PubMed

Wang, Zhaoxia; Li, Li; Wang, Yang

2016-06-01

The aim of the present study was to evaluate the association between Period2 (Per2) and the occurrence and development of ovarian cancer, in addition to evaluating the effect of this gene on the growth and metastasis of ovarian cancer in nude mice xenograft models. The detection of Per2 by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blotting methods at various stages of ovarian cancer in tumor tissue samples was conducted. Nude mice xenograft models of ovarian cancer were constructed using an ovarian cancer cell line and, using a gene transfection technique, exogenous infusion of the recombinant gene, Per2, was performed. To assess for the successful and stable expression of Per2 in the tumor tissue, levels of Per2 expression in the nude mice xenograft models were detected by RT‑qPCR. During the experimental period, the tumor volumes were measured every three days. Two weeks following treatment cessation, the nude mice were sacrificed and the tumor weight and volume were measured. Furthermore, detection of the changes in expression levels of metastasis‑associated gene 1 (MTA‑1) and tumor metastasis suppressor gene, non‑metastasis protein 23‑H1 (nm23‑H1), and the expression change of autophagy‑associated signal transduction pathway, phosphatidylinositol 3‑kinase (PI3K)/protein kinase B (PKB) kinase were analyzed. The findings demonstrated that with ovarian cancer stage development, the expression of Per2 gradually reduced or ceased. In addition, exogenous Per2 was successfully and stably expressed in nude mice tumor tissue samples. Furthermore, in the Per2 overexpression group, MTA‑1 protein expression was significantly reduced when compared with the phosphate‑buffered saline (PBS) control and empty plasmid groups, while nm23‑H1 protein expression was significantly higher when compared with those two groups. The expression levels of PI3K and PKB kinase, which are marker proteins of the autophagy associated signaling pathway PI3K/PKB, were significantly downregulated, when compared with the PBS control and empty plasmid groups (P<0.001). Thus, it was demonstrated that Per2 is closely associated with the development of ovarian cancer, and late‑stage ovarian cancer is associated with Per2 mutation or deletion. Per2 overexpression, via exogenous infusion reduced the ovarian cancer growth rate, which was demonstrated by a significant increase in the tumor inhibition rate. In addition, Per2 may inhibit the expression of MTA‑1 and promote the expression of nm23‑H1 to restrict ovarian tumor growth and metastasis. Finally, it is hypothesized that Per2 affects autophagy by interfering with the PI3K/PKB signaling pathway, causing inhibition of tumor angiogenesis in order to inhibit tumor growth.

Pathways to Understanding Ovarian Cancer, Epidemiology, Genetic Susceptibility, and Survival

DTIC Science & Technology

2011-05-01

develop from the fallopian tubes while others develop from the ovarian surface epithelium through Mullerian inclusions or endometriosis implants...RAS and BRA F mutations leading to low grade serous and m ucinous carcinomas, 2) endometriosis implants or transformation into endometrioid... endometriosis (p for heterogeneity = 0.0002), w e observed significant associations only with dominant tumors. Interestingly, IUD use was associated with a

Quantitative expression patterns of GDF9 and BMP15 genes in sheep ovarian follicles grown in vivo or cultured in vitro.

PubMed

Kona, S S R; Praveen Chakravarthi, V; Siva Kumar, A V N; Srividya, D; Padmaja, K; Rao, V H

2016-01-15

Quantitative patterns of expression of the growth differentiation factor 9 (GDF9) and bone morphogenic protein 15 (BMP15) genes in different development stages of in vivo and in vitro grown ovarian follicles in sheep were studied for the first time. Both GDF9 and BMP15 were expressed in the cumulus cells and oocytes at all the development stages of in vivo and in vitro grown ovarian follicles. Growth differentiation factor 9 and bone morphogenic protein 15 exhibited stage-specific undulations in the expression in the cumulus cells and oocytes isolated from in vivo grown ovarian follicles. These undulations could be related to discrete development events during the ovarian follicle development. The expression of GDF9 and BMP15 was highest (3.38 ± 0.02 and 2.69 ± 0.06, respectively; P ≤ 0.05) in the primordial follicles compared with preantral, early antral, antral, and large antral stages. Similarly, GDF9 and BMP15 expression in the cumulus cells (0 ± 0.16 and 0 ± 0.07) and oocytes (1.47 ± 0.07 and 1.32 ± 0.03) was lowest (P ≤ 0.05) in the in vivo grown antral follicles. In the cultured follicles, the stage-specific undulations observed in the expression of GDF9 and BMP15 in the in vivo grown follicles were either different or abolished. For example, in the oocytes from in vitro grown follicles, the expression of BMP15 did not change as the development progressed all the way from preantral to large antral follicle stage although in the oocytes from in vivo grown follicles BMP15 expression exhibited stage-specific variations. It is concluded that GDF9 and BMP15 follow a stage-specific pattern of expression during the in vivo development of ovarian follicles in sheep, and in vitro culture altered the stage-specific changes in the expression of these two genes. Copyright © 2016 Elsevier Inc. All rights reserved.

A combination of circulating miRNAs for the early detection of ovarian cancer

PubMed Central

Yokoi, Akira; Yoshioka, Yusuke; Hirakawa, Akihiro; Yamamoto, Yusuke; Ishikawa, Mitsuya; Ikeda, Shun-ichi; Kato, Tomoyasu; Niimi, Kaoru; Kajiyama, Hiroaki; Kikkawa, Fumitaka; Ochiya, Takahiro

2017-01-01

Ovarian cancer is the leading cause of gynecologic cancer mortality, due to the difficulty of early detection. Current screening methods lack sufficient accuracy, and it is still challenging to propose a new early detection method that improves patient outcomes with less-invasiveness. Although many studies have suggested the utility of circulating microRNAs in cancer detection, their potential for early detection remains elusive. Here, we develop novel predictive models using a combination of 8 circulating serum miRNAs. This method was able to successfully distinguish ovarian cancer patients from healthy controls (area under the curve, 0.97; sensitivity, 0.92; and specificity, 0.91) and early-stage ovarian cancer from patients with benign tumors (0.91, 0.86 and 0.83, respectively). This method also enables subtype classification in 4 types of epithelial ovarian cancer. Furthermore, it is found that most of the 8 miRNAs were packaged in extracellular vesicles, including exosomes, derived from ovarian cancer cells, and they were circulating in murine blood stream. The circulating miRNAs described in this study may serve as biomarkers for ovarian cancer patients. Early detection and subtype determination prior to surgery are crucial for clinicians to design an effective treatment strategy for each patient, as is the goal of precision medicine. PMID:29163790

Beyond Breast and Ovarian Cancers: PARP Inhibitors for BRCA Mutation-Associated and BRCA-Like Solid Tumors

PubMed Central

O’Sullivan, Ciara C.; Moon, Dominic H.; Kohn, Elise C.; Lee, Jung-Min

2014-01-01

Poly(ADP-ribose) polymerase inhibitors (PARPi) have shown clinical activity in patients with germline BRCA1/2 mutation (gBRCAm)-associated breast and ovarian cancers. Accumulating evidence suggests that PARPi may have a wider application in the treatment of cancers defective in DNA damage repair pathways, such as prostate, lung, endometrial, and pancreatic cancers. Several PARPi are currently in phase I/II clinical investigation, as single-agents and/or combination therapy in these solid tumors. Understanding more about the molecular abnormalities involved in BRCA-like phenotype in solid tumors beyond breast and ovarian cancers, exploring novel therapeutic trial strategies and drug combinations, and defining potential predictive biomarkers are critical to expanding the scope of PARPi therapy. This will improve clinical outcome in advanced solid tumors. Here, we briefly review the preclinical data and clinical development of PARPi, and discuss its future development in solid tumors beyond gBRCAm-associated breast and ovarian cancers. PMID:24616882

Prolactin Alters the Mammary Epithelial Hierarchy, Increasing Progenitors and Facilitating Ovarian Steroid Action.

PubMed

O'Leary, Kathleen A; Shea, Michael P; Salituro, Stephanie; Blohm, Courtney E; Schuler, Linda A

2017-10-10

Hormones drive mammary development and function and play critical roles in breast cancer. Epidemiologic studies link prolactin (PRL) to increased risk for aggressive cancers that express estrogen receptor α (ERα). However, in contrast to ovarian steroids, PRL actions on the mammary gland outside of pregnancy are poorly understood. We employed the transgenic NRL-PRL model to examine the effects of PRL alone and with defined estrogen/progesterone exposure on stem/progenitor activity and regulatory networks that drive epithelial differentiation. PRL increased progenitors and modulated transcriptional programs, even without ovarian steroids, and with steroids further raised stem cell activity associated with elevated canonical Wnt signaling. However, despite facilitating some steroid actions, PRL opposed steroid-driven luminal maturation and increased CD61 + luminal cells. Our findings demonstrate that PRL can powerfully influence the epithelial hierarchy alone and temper the actions of ovarian steroids, which may underlie its role in the development of breast cancer. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Toward in-vivo photoacoustic imaging of human ovarian tissue for cancer detection

NASA Astrophysics Data System (ADS)

Aguirre, Andres; Kumavor, Patrick; Ardeshirpour, Yasaman; Sanders, Mary M.; Brewer, Molly; Zhu, Quing

2011-03-01

Currently, most of the cancers in the ovary are detected when they have already metastasized to other parts of the body. As a result, ovarian cancer has the highest mortality of all gynecological cancers with a 5-year survival rate of 30% or less [1]. The reason is the lack of reliable symptoms as well as the lack of efficacious screening techniques [2,3]. Thus, there is an urgent need to improve the current diagnostic techniques. We have investigated the potential role of co-registered photoacoustic and ultrasound imaging in ovarian cancer detection. In an effort to bring this technique closer to clinical application, we have developed a co-registered ultrasound and photoacoustic transvaginal probe. A fiber coupling assembly has been developed to deliver the light from around the transducer for reflection geometry imaging. Co-registered ultrasound and photoacoustic images of swine ovaries through vagina wall muscle and human ovaries using the aforementioned probe, demonstrate the potential of photoacoustic imaging to non-invasively detect ovarian cancer in vivo.

Suppression of SIK1 by miR-141 in human ovarian cancer cell lines and tissues.

PubMed

Chen, Jin-Long; Chen, Fang; Zhang, Ting-Ting; Liu, Nai-Fu

2016-06-01

Epithelial ovarian cancer (EOC), the sixth most common cancer in women worldwide, is the most commonly fatal gynecologic malignancy in developed countries. One of the main reasons for this is that relatively little was known about the molecular events responsible for the development of this highly aggressive disease. In the present study, we demonstrated that salt‑inducible kinase 1 (SIK1; which is also known as MSK/SIK/SNF1LK) was downregulated in ovarian cancer tissue samples. Using HEY ovarian cancer cells, we noted that SIK1 overexpression inhibited proliferation as well as cancer stem cell-associated traits. Silencing SIK1 promoted the proliferation of the EG ovarian cancer cell line. We performed an analysis of potential microRNAs (miRNAs or miRs) target sites using three commonly used prediction algorithms: miRanda, TargetScan and PicTar. All three algorithms predicted that miR-141 targets the 3'UTR of SIK1. Subsequent experiments not only confirmed this prediction, but also showed that miR-141 was associated with the progression of this disease. Finally, we found that miR-141 promoted proliferation of EG cells, whereas silencing miR-141 restored SIK1 expression and inhibited the proliferation of the HEY cells. Elucidating the molecular mechanism of ovarian cancer not only enables us to further understand the pathogenesis and progression of the disease, but also provides new targets for effective therapies.

Inovium Ovarian Rejuvenation Trials

ClinicalTrials.gov

2018-05-18

Perimenopausal Disorder; Menopause; Menopause, Premature; Menopause Related Conditions; Menopause Premature Symptomatic; Menopause Premature Asymptomatic; Premature Ovarian Failure; Premature Ovarian Failure, Familial; Premature Ovarian Failure 2A; Premature Ovarian Failure 3; Premature Ovarian Failure 4; Premature Ovarian Failure 1; Premature Ovarian Failure 5; Premature Ovarian Failure 6; Premature Ovarian Failure 7; Premature Ovarian Failure 9; Premature Ovarian Failure 8; Infertility; Infertility, Female; Infertility Unexplained

Potential role of retinoids in ovarian physiology and pathogenesis of polycystic ovary syndrome.

PubMed

Jiang, Yanwen; Li, Chunjin; Chen, Lu; Wang, Fengge; Zhou, Xu

2017-06-01

Retinoids (retinol and its derivatives) are required for maintaining vision, immunity, barrier function, reproduction, embryogenesis, cell proliferation and differentiation. Furthermore, retinoid signaling plays a key role in initiating meiosis of germ cells of the mammalian fetal ovary. Recently, studies indicated that precise retinoid level regulation in the ovary provides a molecular control of ovarian development, steroidogenesis and oocyte maturation. Besides, abnormal retinoid signaling may be involved in the pathogenesis of polycystic ovary syndrome (PCOS), one of the most common ovarian endocrinopathies in reproductive-aged women worldwide. This review primarily summarizes recent advancements made in investigating the action of retinoid signaling in ovarian physiology as well as the abnormal retinoid signaling in PCOS. Copyright © 2017. Published by Elsevier B.V.

The evolution of life-history variation in fishes, with particular reference to flatfishes

NASA Astrophysics Data System (ADS)

Roff, Derek A.

This paper explores four aspects of the evolution of life-history variation in fish, with particular reference to the flatfishes: 1. genetic variation and evolutionary response; 2. the size and age at first reproduction; 3. adult lifespan and variation in recruitment; 4. the relationship between reproductive effort and age. Evolutionary response may be limited by previous evolutionary pathways (phylogenetic variation) or by lack of genetic variation due to selection for a single trait. Estimates of heritability suggest, as predicted, that selection is stronger on life-history traits than morphological traits; but there is still adequate genetic variation to permit fairly rapid evolutionary changes. Several approaches to the analysis of the optimal age and size at first reproduction are discussed in the light of a general life-history model based on the assumption that natural selection maximizes r or R 0. It is concluded that one of the most important areas of future research is the relationship between reproduction and mortality. Murphy's hypothesis that the reproductive lifespan should increase with variation in spawning success is shown to be incorrect for fish, at least at the level of interspecific comparison. The model of Charlesworth & León predicting the sufficient condition for reproductive effort to increase with age is tested: in 28 of 31 cases the model predicts an increase of reproductive effort with age. These results suggest that, in general, reproductive effort should increase with age in fish. This prediction is confirmed in the 15 species for which adequate data exist.

Depth and substrate as determinants of distribution of juvenile flathead sole (Hippoglossoides elassodon) and rock sole (Pleuronectes bilineatus), in Kachemak Bay, Alaska

USGS Publications Warehouse

Abookire, Alisa A.; Norcross, Brenda L.

1998-01-01

Three transects in Kachemak Bay, Alaska, were sampled in September 1994, May and August 1995, and February, May, and August 1996. Juvenile flathead sole, Hippoglossoides elassodon, and rock sole, Pleuronectes bilineatus, were the most abundant flatfishes, comprising 65-85% of all fiatfishes captured at any period. Collections of fish and sediments were made at regular depth contour intervals of l0 m. Habitat distribution was described by depth at 10 m increments and sediment percent weights of gravel, sand, and mud. Year-round habitat of flathead sole age-0 was primarily from 40 to 60 m, and age-1 habitat was primarily from 40 to 80 m. Summer habitat of rock sole age-0 and -1 was from 10 to 30 m, and in winter they moved offshore to depths of up to 150 m. Both age classes of flathead sole were most abundant on mixed mud sediments, while age-1 were also in high abundance on muddy sand sediments. Rock sole age-0 and -1 were most abundant on sand, though age-1 were also found on a variety of sediments both finer and coarser grained than sand. Flathead sole and rock sole had distinctive depth and sediment habitats. When habitat overlap occurred between the species, it was most often due to rock sole moving offshore in the winter. Abundances were not significantly different among seasons for age-1 flatfishes.

The presence of centrioles and centrosomes in ovarian mature cystic teratoma cells suggests human parthenotes developed in vitro can differentiate into mature cells without a sperm centriole

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Bo Yon, E-mail: boyonlee@gmail.com; Shim, Sang Woo; Kim, Young Sun

Highlights: Black-Right-Pointing-Pointer The sperm centriole is the progenitor of centrosomes in all somatic cells. Black-Right-Pointing-Pointer Centrioles and centrosomes exist in parthenogenetic ovarian teratoma cells. Black-Right-Pointing-Pointer Without a sperm centriole, parthenogenetic oocytes produce centrioles and centrosomes. Black-Right-Pointing-Pointer Parthenogenetic human oocytes can develop and differentiate into mature cells. -- Abstract: In most animals, somatic cell centrosomes are inherited from the centriole of the fertilizing spermatozoa. The oocyte centriole degenerates during oogenesis, and completely disappears in metaphase II. Therefore, the embryos generated by in vitro parthenogenesis are supposed to develop without any centrioles. Exceptional acentriolar and/or acentrosomal developments are possible in mice andmore » in some experimental cells; however, in most animals, the full developmental potential of parthenogenetic cells in vitro and the fate of their centrioles/centrosomes are not clearly understood. To predict the future of in vitro human parthenogenesis, we explored the centrioles/centrosomes in ovarian mature cystic teratoma cells by immunofluorescent staining and transmission electron microscopy. We confirmed the presence of centrioles and centrosomes in these well-known parthenogenetic ovarian tumor cells. Our findings clearly demonstrate that, even without a sperm centriole, parthenotes that develop from activated oocytes can produce their own centrioles/centrosomes, and can even develop into the well-differentiated mature tissue.« less

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

ClinicalTrials.gov

2018-01-31

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

[Explore microcosmic connection between autophagy mechanism and follicular development based on "kidney governing reproduction" theory].

PubMed

Bai, Jun; Wu, Ke-Ming; Gao, Ran-Ran

2018-03-01

In the theory of traditional Chinese medicine(TCM) that "kidney storing essence and governing reproduction", reproductive essence is an important part of the kidney essence and acts as the original material of offspring embryos. Sperm, oocyte and zygote should be all included in the range of reproductive essence. Ovum is the essence of reproduction from inborn. The follicles maturation depends on the quality of oocyte and the vigor of kidney essence. Meanwhile, discharge of mature ovum relies on the stimulation and promotion by kidney Qi. Autophagy almost exists in different cells stages and all various of mammalian cells. Many studies have found that autophagy not only participates in the formation of follicles, but also in every phase of the follicles development, and is involved in the occurrence and development of ovarian diseases. Recently, more and more scholars believe that autophagy is a new field to explore the microcosmic relationship between autophagy and TCM. Kidney-nourishing TCM could promote follicular growth and improve variety clinical symptoms by inhibiting the apoptosis of ovarian granulosa cells and reducing follicular atresia. Meanwhile, apoptosis of ovarian granulosa cells is closely related to autophagy of ovarian granulosa cells. In order to provide some theoretical foundation for kidney-nourishing therapy's promoting effect on follicular growth and improving effect on ovarian function, also to further explore the molecular mechanism of kidney-nourishing medicine in promoting follicular development, this paper would explain the microcosmic relationship between autophagy and follicular development based on the theory of "kidney governing reproduction". All of these would be of great significance to prevent and intervene the diseases of reproductive system timely and effectively. Copyright© by the Chinese Pharmaceutical Association.

Pubertal development and primary ovarian insufficiency in female survivors of embryonal brain tumors following risk-adapted craniospinal irradiation and adjuvant chemotherapy.

PubMed

DeWire, Mariko; Green, Daniel M; Sklar, Charles A; Merchant, Thomas E; Wallace, Dana; Lin, Tong; Vern-Gross, Tamara; Kun, Larry E; Krasin, Matthew J; Boyett, James M; Wright, Karen D; Wetmore, Cynthia; Broniscer, Alberto; Gajjar, Amar

2015-02-01

Female survivors of central nervous system (CNS) tumors are at an increased risk for gonadal damage and variations in the timing of puberty following radiotherapy and alkylating agent-based chemotherapy. Clinical and laboratory data were obtained from 30 evaluable female patients with newly diagnosed embryonal CNS tumors treated on a prospective protocol (SJMB 96) at St. Jude Children's Research Hospital (SJCRH). Pubertal development was evaluated by Tanner staging. Primary ovarian insufficiency (POI) was determined by Tanner staging and FSH level. Females with Tanner stage I-II and FSH > 15 mIU/ml, or Tanner stage III-V, FSH > 25 mIU/ml and FSH greater than LH were defined to have ovarian insufficiency. Recovery of ovarian function was defined as normalization of FSH without therapeutic intervention. Median length of follow-up post completion of therapy was 7.2 years (4.0-10.8 years). The cumulative incidence of pubertal onset was 75.6% by the age of 13. Precocious puberty was observed in 11.1% and delayed puberty in 11.8%. The cumulative incidence of POI was 82.8%, though recovery was observed in 38.5%. Treatment for primary CNS embryonal tumors may cause variations in the timing of pubertal development, impacting physical and psychosocial development. Female survivors are at risk for POI, a subset of whom will recover function over time. Further refinement of therapies is needed in order to reduce late ovarian insufficiency. Pediatr Blood Cancer 2015;62:329-334. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc.

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

ClinicalTrials.gov

2018-06-04

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

The oncogenic gene fusion TMPRSS2: ERG is not a diagnostic or prognostic marker for ovarian cancer

PubMed Central

Huang, Lillian; Schauer, Isaiah G; Zhang, Jing; Mercado-Uribe, Imelda; Deavers, Michael T; Huang, Jiaoti; Liu, Jinsong

2011-01-01

TMPRSS2:ERG is a gene fusion resulting from the chromosomal rearrangement of the androgen-regulated TMPRSS2 gene and the ETS transcription factor ERG, leading to the over-expression of the oncogenic molecule ERG. This gene rearrangement has been found in approximately half of all prostate cancers and ERG overexpression is considered as a novel diagnostic marker for prostate carcinoma. However, little is known about the role of the TMPRSS2:ERG gene fusion in ovarian cancer. The purpose of this study was to test ERG expression in ovarian cancer and its potential as a diagnostic marker for ovarian carcinoma progression. A tissue microarray containing 180 ovarian cancer tissues of various pathological types and grades were examined by immunohistochemical analysis for expression of ERG. We also used 40 prostate carcinoma tissues and 40 normal tissues for comparison in parallel experiments. ERG-positive expression was detected in 40% of the prostate tumor cancer, as well as in internal positive control endothelial cells, confirming over-expression of ERG in prostate cancer at relatively the same rate observed by others. In contrast, all of the ovarian tumor patient tissues of varying histologic types were ERG-negative, despite some positivity in endothelial cells. These results suggest that the oncogenic gene fusion TMPRSS2:ERG does not occur in ovarian cancer relative to prostate cancer. Therefore, development of ERG expression profile would not be a useful diagnostic or prognostic marker for ovarian cancer patient screening. PMID:22076164

The oncogenic gene fusion TMPRSS2: ERG is not a diagnostic or prognostic marker for ovarian cancer.

PubMed

Huang, Lillian; Schauer, Isaiah G; Zhang, Jing; Mercado-Uribe, Imelda; Deavers, Michael T; Huang, Jiaoti; Liu, Jinsong

2011-01-01

TMPRSS2:ERG is a gene fusion resulting from the chromosomal rearrangement of the androgen-regulated TMPRSS2 gene and the ETS transcription factor ERG, leading to the over-expression of the oncogenic molecule ERG. This gene rearrangement has been found in approximately half of all prostate cancers and ERG overexpression is considered as a novel diagnostic marker for prostate carcinoma. However, little is known about the role of the TMPRSS2:ERG gene fusion in ovarian cancer. The purpose of this study was to test ERG expression in ovarian cancer and its potential as a diagnostic marker for ovarian carcinoma progression. A tissue microarray containing 180 ovarian cancer tissues of various pathological types and grades were examined by immunohistochemical analysis for expression of ERG. We also used 40 prostate carcinoma tissues and 40 normal tissues for comparison in parallel experiments. ERG-positive expression was detected in 40% of the prostate tumor cancer, as well as in internal positive control endothelial cells, confirming over-expression of ERG in prostate cancer at relatively the same rate observed by others. In contrast, all of the ovarian tumor patient tissues of varying histologic types were ERG-negative, despite some positivity in endothelial cells. These results suggest that the oncogenic gene fusion TMPRSS2:ERG does not occur in ovarian cancer relative to prostate cancer. Therefore, development of ERG expression profile would not be a useful diagnostic or prognostic marker for ovarian cancer patient screening.

A draft map of the human ovarian proteome for tissue engineering and clinical applications.

PubMed

Ouni, Emna; Vertommen, Didier; Chiti, Maria Costanza; Dolmans, Marie-Madeleine; Amorim, Christiani Andrade

2018-02-23

Fertility preservation research in women today is increasingly taking advantage of bioengineering techniques to develop new biomimetic materials and solutions to safeguard ovarian cell function and microenvironment in vitro and in vivo. However, available data on the human ovary are limited and fundamental differences between animal models and humans are hampering researchers in their quest for more extensive knowledge of human ovarian physiology and key reproductive proteins that need to be preserved. We therefore turned to multi-dimensional label-free mass spectrometry to analyze human ovarian cortex, as it is a high-throughput and conclusive technique providing information on the proteomic composition of complex tissues like the ovary. In-depth proteomic profiling through two-dimensional liquid chromatography-mass spectrometry, western blot, histological and immunohistochemical analyses, and data mining helped us to confidently identify 1,508 proteins. Moreover, our method allowed us to chart the most complete representation so far of the ovarian matrisome, defined as the ensemble of extracellular matrix proteins and associated factors, including more than 80 proteins. In conclusion, this study will provide a better understanding of ovarian proteomics, with a detailed characterization of the ovarian follicle microenvironment, in order to enable bioengineers to create biomimetic scaffolds for transplantation and three-dimensional in vitro culture. By publishing our proteomic data, we also hope to contribute to accelerating biomedical research into ovarian health and disease in general. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

Knockdown of RhoA expression alters ovarian cancer biological behavior in vitro and in nude mice.

PubMed

Wang, Xiaoxia; Jiang, Wenyan; Kang, Jiali; Liu, Qicai; Nie, Miaoling

2015-08-01

RhoA regulates cell proliferation, migration, angiogenesis and gene expression. Altered RhoA activity contributes to cancer progression. The present study investigated the effects of RhoA knockdown on the regulation of ovarian cancer biological behavior in vitro and in nude mice. The expression of RhoA was knocked down using a lentivirus carrying RhoA short hairpin RNA (shRNA) in ovarian cancer cells and was confirmed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. The altered ovarian cancer biological behaviors were assayed by cell viability, terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling (TUNEL), migration, invasion, and nude mice tumorigenicity assays, while the altered gene expression was detected by RT-qPCR and western blot analysis. The results showed that lentivirus-carrying RhoA shRNA significantly suppressed RhoA expression in ovarian cancer cells, which suppressed tumor cell viability, migration, invasion and adhesion in vitro. RhoA silencing also inhibited the tumorigenicity of ovarian cancer cells in nude mice, which was characterized by the suppression of tumor xenograft formation and growth and induction of tumor cell apoptosis. The results of the present study demonstrated that knockdown of RhoA expression had a significant antitumor effect on ovarian cancer cells in vitro and in nude mice, suggesting that RhoA may be a target for the development of a novel therapeutic strategy in the control of ovarian cancer.

New Mouse Model May Aid in Developing Effective Therapies for Ovarian Cancer | Poster

Cancer.gov

By Frank Blanchard, Staff Writer A new genetically engineered mouse model appears promising as an effective tool for preclinical testing of novel therapies for ovarian cancer, which tends to be diagnosed in late stage. There are few effective treatments for the disease.

A Specific Mixture of Nutrients Suppresses Ovarian Cancer A-2780 Tumor Incidence, Growth, and Metastasis to Lungs.

PubMed

Roomi, Mohd Waheed; Kalinovsky, Tatiana; Rath, Matthias; Niedzwiecki, Aleksandra

2017-03-18

Ovarian cancer is the deadliest gynecological malignancy in women, and fifth leading cause of death. Despite advances made in chemotherapy and surgery, the average time of clinical remission is approximately 2 years and the 5-year survival rate is 45%. Thus, there is an urgent need for the development of a novel therapeutic approach to ovarian cancer treatment. We investigated the effect of a specific nutrient mixture (EPQ) containing ascorbic acid, lysine, proline, green tea extract, and quercetin on human ovarian cancer cell A-2780 in vivo and in vitro. Athymic female nude mice (n = 12) were all inoculated intraperitoneally (IP) with 2 × 10⁶ cells in 0.1 mL of phosphate buffered saline (PBS) and randomly divided into two groups. Upon injection, the Control group (n = 6) was fed a regular diet and the EPQ group (n = 6) a regular diet supplemented with 0.5% EPQ. Four weeks later, the mice were sacrificed and tumors that developed in the ovary were excised, weighed, and processed for histology. Lungs were inspected for metastasis. In vitro, A-2780 cells were cultured in Dulbecco modified Eagle medium supplemented with 10% FBS and antibiotics. At near confluence, cells were treated with EPQ in triplicate at concentrations between 0 and 1000 μg/mL. Cell proliferation was measured via MTT assay, MMP-9 secretion via gelatinase zymography, invasion through Matrigel and morphology via hematoxylin and eosin (H & E) staining. All Control mice developed large ovarian tumors, whereas 5 out of 6 mice in the EPQ group developed no tumors, and one, a small tumor. Control mice also showed lung metastasis in 6 out of 6 mice, while no lung metastasis was evident in EPQ mice. Zymography demonstrated only MMP-9 expression, which EPQ inhibited in a dose-dependent fashion, with virtual total block at 250 μg/mL concentration. EPQ significantly inhibited invasion through Matrigel with total block at 250 μg/mL concentration. MTT showed dose-dependent inhibition of cell proliferation with EPQ, and H & E staining showed no morphological changes below 500 μg/mL EPQ. These results suggest that EPQ has therapeutic potential in the treatment of ovarian cancer by significantly suppressing ovarian tumor incidence and growth and lung metastasis, and by inhibiting MMP-9 secretion and invasion of A-2780 ovarian cancer cells.

Risk-reducing surgery on the uterine adnexa: timing and type of surgical treatment, and pathology report.

PubMed

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

2016-10-01

Inherited mutations in BRCA1 and BRCA2 increase significantly the risk of developing breast and ovarian cancers, and they have been associated with increased risks of developing other types of cancer. Although screening programs have been implemented in order to detect cancers at the early stage, they resulted ineffective. To date, risk-reducing bilateral salpingo-oophorectomy represents the only procedure allowing reducing the incidence of ovarian cancer and increasing survival among BRCA1 and -2 mutation carriers. In the present review we will discuss the advantages and disadvantages related to the execution of prophylactic surgery, thus underlying possible beneficial and detrimental effects of this kind of surgery in premenopausal women. Additionally, we will investigate further therapeutic strategies aimed to reduce the risk of developing ovarian cancer, without affected patients' hormonal status.

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

MicroRNA-133b targets glutathione S-transferase π expression to increase ovarian cancer cell sensitivity to chemotherapy drugs.

PubMed

Chen, Shuo; Jiao, Jin-Wen; Sun, Kai-Xuan; Zong, Zhi-Hong; Zhao, Yang

2015-01-01

Accumulating studies reveal that aberrant microRNA (miRNA) expression can affect the development of chemotherapy drug resistance by modulating the expression of relevant target proteins. The aim of this study was to investigate the role of miR-133b in the development of drug resistance in ovarian cancer cells. We examined the levels of miR-133b expression in ovarian carcinoma tissues and the human ovarian carcinoma cell lines (A2780, A2780/DDP and A2780/Taxol, respectively). We determined the cell viability of these cell lines treated with cisplatin or paclitaxel in the presence or absence of miR-133b or anti-miR-133b transfection using the MTT assay. Reverse transcription polymerase chain reaction and Western blotting were used to assess the mRNA and protein expression levels of two drug-resistance-related genes: glutathione S-transferase (GST)-π and multidrug resistance protein 1 (MDR1). The dual-luciferase reporter assay was used to detect the promoter activity of GST-π in the presence and absence of miR-133b. The expression of miR-133b was significantly lower in primary resistant ovarian carcinomas than in the chemotherapy-sensitive carcinomas (P<0.05), and the same results were found in primary resistant ovarian cell lines (A2780/Taxol and A2780/DDP) compared to the chemotherapy-sensitive cell line (A2780; P<0.05). Following miR-133b transfection, four cell lines showed increased sensitivity to paclitaxel and cisplatin, while anti-miR-133b transfection reduced cell sensitivity to paclitaxel and cisplatin. Dual-luciferase reporter assay showed that miR-133b interacted with the 3'-untranslated region of GST-π. Compared to controls, the mRNA and protein levels of MDR1 and GST-π were downregulated after miR-133b transfection and upregulated after anti-miR-133b transfection. MicroRNA-133b may reduce ovarian cancer drug resistance by silencing the expression of the drug-resistance-related proteins, GST-π and MDR1. In future, the combination of miR-133b with chemotherapy agents may prevent the development of drug resistance in ovarian cancers.

Microchip ELISA coupled with cell phone to detect ovarian cancer HE4 biomarker in urine.

PubMed

Wang, ShuQi; Akbas, Ragip; Demirci, Utkan

2015-01-01

Ovarian cancer is a leading cause of death from gynecologic cancers in the USA, and early diagnosis can potentially increase 5-year survival rate. Detection of biomarkers derived from hyperplasia of epithelial tissue by enzyme-linked immunosorbent assay (ELISA) proves to be a practical way of early diagnosis of ovarian cancer. However, ELISA is commonly performed in a laboratory setting, and it cannot be used in a clinical setting for on-site consultation. We have shown a microchip ELISA that detects HE4, an ovarian cancer biomarker, from urine using a cell phone integrated with a mobile application for imaging and data analysis. In microchip ELISA, HE4 from urine was first absorbed on the surface; the primary and secondary antibodies were subsequently anchored on the surface via immuno-reaction; and addition of substrate led to color development because of enzymatic labeling. The microchip after color development was imaged using a cell phone, and the color intensity was analyzed by an integrated mobile application. By comparing with an ELISA standard curve, the concentration of HE4 was reported on the cell phone screen. The presented microchip ELISA coupled with a cell phone is portable as opposed to traditional ELISA, and this method can facilitate the detection of ovarian cancer at the point-of-care (POC).

Chick chorioallantoic membrane assay as an in vivo model to study the effect of nanoparticle-based anticancer drugs in ovarian cancer.

PubMed

Vu, Binh Thanh; Shahin, Sophia Allaf; Croissant, Jonas; Fatieiev, Yevhen; Matsumoto, Kotaro; Le-Hoang Doan, Tan; Yik, Tammy; Simargi, Shirleen; Conteras, Altagracia; Ratliff, Laura; Jimenez, Chiara Mauriello; Raehm, Laurence; Khashab, Niveen; Durand, Jean-Olivier; Glackin, Carlotta; Tamanoi, Fuyuhiko

2018-06-04

New therapy development is critically needed for ovarian cancer. We used the chicken egg CAM assay to evaluate efficacy of anticancer drug delivery using recently developed biodegradable PMO (periodic mesoporous organosilica) nanoparticles. Human ovarian cancer cells were transplanted onto the CAM membrane of fertilized eggs, resulting in rapid tumor formation. The tumor closely resembles cancer patient tumor and contains extracellular matrix as well as stromal cells and extensive vasculature. PMO nanoparticles loaded with doxorubicin were injected intravenously into the chicken egg resulting in elimination of the tumor. No significant damage to various organs in the chicken embryo occurred. In contrast, injection of free doxorubicin caused widespread organ damage, even when less amount was administered. The lack of toxic effect of nanoparticle loaded doxorubicin was associated with specific delivery of doxorubicin to the tumor. Furthermore, we observed excellent tumor accumulation of the nanoparticles. Lastly, a tumor could be established in the egg using tumor samples from ovarian cancer patients and that our nanoparticles were effective in eliminating the tumor. These results point to the remarkable efficacy of our nanoparticle based drug delivery system and suggests the value of the chicken egg tumor model for testing novel therapies for ovarian cancer.

Nano-Encapsulation of Arsenic Trioxide Enhances Efficacy against Murine Lymphoma Model while Minimizing Its Impact on Ovarian Reserve In Vitro and In Vivo

PubMed Central

Raja, Meera R.; Jozefik, Jennifer K.; Spaho, Lidia; Chen, Haimei; Bally, Marcel B.; Mazar, Andrew P.; Avram, Michael J.; Winter, Jane N.; Gordon, Leo I.; Shea, Lonnie D.; O’Halloran, Thomas V.; Woodruff, Teresa K.

2013-01-01

Advances in cancer therapy have increased the rate of survival of young cancer patients; however, female lymphoma patients frequently face a temporary or permanent loss of fertility when treated with traditional cytotoxic agents. The potential loss of fertility is an important concern that can influence treatment decisions for many premenopausal cancer patients. The negative effect of chemotherapeutic agents and treatment protocols to patients’ fertility–referred to as fertotoxicity–are thus an increasingly important cancer survivorship issue. We have developed a novel nanoscale formulation of arsenic trioxide, a potent drug for treatment of hematological malignancies, and demonstrate that it has significantly better activity in a murine lymphoma model than the free drug. In parallel, we have developed a novel in vitro assay of ovarian follicle function that predicts in vivo ovarian toxicity of therapeutic agents. Our results reveal that the nanotherapeutic agent is not only more active against lymphoma, but is fertoprotective, i.e., it is much less deleterious to ovarian function than the parent drug. Thus, our in vitro assay allows rapid evaluation of both established and experimental anticancer drugs on ovarian reserve and can inform the selection of efficacious and fertility-sparing treatment regimens for reproductive-age women diagnosed with cancer. PMID:23526987

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

ClinicalTrials.gov

2018-05-01

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

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

ClinicalTrials.gov

2018-04-24

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

Leucine aminopeptidase, HlLAP, from the ixodid tick Haemaphysalis longicornis, plays vital roles in the development of oocytes.

PubMed

Hatta, Takeshi; Tsuji, Naotoshi; Miyoshi, Takeharu; Islam, M Khyrul; Alim, M Abdul; Yamaji, Kayoko; Anisuzzaman; Fujisaki, Kozo

2010-06-01

Female ixodid ticks are amazing invertebrate animals which efficiently convert a large amount of nutrients derived from their ingested blood meals into eggs. Although oocyte development (vitellogenesis) in ticks is triggered by a blood meal and is assumed to be supported by nutrition derived from ovarian cells connecting oocytes, little is known about the ovarian molecules processing nutrient materials for the vitellogenesis. In this study, we have suggested a putative function of leucine aminopeptidase (HlLAP) in the ovary of parthenogenetic adult ixodid tick Haemaphysalis longicornis regarding a negative output of reproduction following disruption of HlLAP gene by RNA interference. Endogenous HlLAP was shown to be localized in the ovarian cells, including ovarian epithelial and pedicel cells which were assumed to provide nutrients for the developing oocytes. Histological studies demonstrated that a majority of immature oocytes in HlLAP gene knockdown ticks were transformed into abnormal morpho-histological oocytes with vacuolated cytoplasm and/or condensed nucleus. Taken together, a reduction of the numbers of laid eggs in the HlLAP gene knockdown ticks may be due to the degeneration of immature oocytes following deprivation of nutrients such as amino acids supplied not only by midgut HlLAP but also by the ovarian HlLAP. Regulation of the tick molecules involved in nutrient metabolism for the reproduction, including blood digestion and vitellogenesis, would help in controlling the tick population and tick-borne pathogens.

Mechanisms of oocyte development in European sea bass (Dicentrarchus labrax L.): investigations via application of unilateral ovariectomy.

PubMed

García-López, Ángel; Sánchez-Amaya, María I; Tyler, Charles R; Prat, Francisco

2011-08-01

Unilateral ovariectomy (ULO) was performed in European sea bass (Dicentrarchus labrax L.) during late pre-vitellogenesis/early vitellogenesis. Plasma steroid levels and the expression of a suite of potential oogenesis-relevant genes in the ovary, brain, and pituitary were evaluated with the aim of understanding their involvement in the compensatory oocyte development occurring within the remaining ovarian lobe. After 69 days of surgery the remaining ovarian lobe in ULO fish was gravimetrically equivalent to an intact-paired ovary of sham operated, control fish. This compensatory ovarian growth was based on an increased number of early perinucleolar oocytes and mid-late stage vitellogenic follicles without an apparent recruitment of primary oocytes into the secondary growth phase. Plasma steroid levels were similar in ULO and control females at all time points analyzed, suggesting an increased steroid production of the remaining ovarian lobe in hemi-castrated females. Results of the gene expression survey conducted indicate that the signaling pathways mediated by Fsh and Gnrh1 constitute the central axes orchestrating the observed ovarian compensatory growth. In addition, steroid receptors, Star protein, Igfs, and members of the transforming growth factor beta superfamily including anti-Mullerian hormone and bone morphogenetic protein 4 were identified as potentially relevant players within this process, although their specific actions and interactions remain to be established. Our results demonstrate that ULO provides an excellent in vivo model for elucidating the interconnected endocrine and molecular mechanisms controlling oocyte development in European sea bass.

Cigarette smoking is associated with adverse survival among women with ovarian cancer: Results from a pooled analysis of 19 studies.

PubMed

Praestegaard, Camilla; Jensen, Allan; Jensen, Signe M; Nielsen, Thor S S; Webb, Penelope M; Nagle, Christina M; DeFazio, Anna; Høgdall, Estrid; Rossing, Mary Anne; Doherty, Jennifer A; Wicklund, Kristine G; Goodman, Marc T; Modugno, Francesmary; Moysich, Kirsten; Ness, Roberta B; Edwards, Robert; Matsuo, Keitaro; Hosono, Satoyo; Goode, Ellen L; Winham, Stacey J; Fridley, Brooke L; Cramer, Daniel W; Terry, Kathryn L; Schildkraut, Joellen M; Berchuck, Andrew; Bandera, Elisa V; Paddock, Lisa E; Massuger, Leon F; Wentzensen, Nicolas; Pharoah, Paul; Song, Honglin; Whittemore, Alice; McGuire, Valerie; Sieh, Weiva; Rothstein, Joseph; Anton-Culver, Hoda; Ziogas, Argyrios; Menon, Usha; Gayther, Simon A; Ramus, Susan J; Gentry-Maharaj, Alexandra; Wu, Anna H; Pearce, Celeste L; Pike, Malcolm; Lee, Alice W; Sutphen, Rebecca; Chang-Claude, Jenny; Risch, Harvey A; Kjaer, Susanne K

2017-06-01

Cigarette smoking is associated with an increased risk of developing mucinous ovarian tumors but whether it is associated with ovarian cancer survival overall or for the different histotypes is unestablished. Furthermore, it is unknown whether the association between cigarette smoking and survival differs according to strata of ovarian cancer stage at diagnosis. In a large pooled analysis, we evaluated the association between various measures of cigarette smoking and survival among women with epithelial ovarian cancer. We obtained data from 19 case-control studies in the Ovarian Cancer Association Consortium (OCAC), including 9,114 women diagnosed with ovarian cancer. Cox regression models were used to estimate adjusted study-specific hazard ratios (HRs), which were combined into pooled hazard ratios (pHR) with corresponding 95% confidence intervals (CIs) under random effects models. Overall, 5,149 (57%) women died during a median follow-up period of 7.0 years. Among women diagnosed with ovarian cancer, both current (pHR = 1.17, 95% CI: 1.08-1.28) and former smokers (pHR = 1.10, 95% CI: 1.02-1.18) had worse survival compared with never smoking women. In histotype-stratified analyses, associations were observed for mucinous (current smoking: pHR = 1.91, 95% CI: 1.01-3.65) and serous histotypes (current smoking: pHR = 1.11, 95% CI: 1.00-1.23; former smoking: pHR = 1.12, 95% CI: 1.04-1.20). Further, our results suggested that current smoking has a greater impact on survival among women with localized than disseminated disease. The identification of cigarette smoking as a modifiable factor associated with survival has potential clinical importance as a focus area to improve ovarian cancer prognosis. © 2017 UICC.

Polymorphisms in BRCA1 and BRCA2 and risk of epithelial ovarian cancer.

PubMed

Wenham, Robert M; Schildkraut, Joellen M; McLean, Kia; Calingaert, Brian; Bentley, Rex C; Marks, Jeffrey; Berchuck, Andrew

2003-10-01

Because inherited BRCA1 or BRCA2 mutations strikingly increase ovarian cancer risk, polymorphisms in these genes could represent low penetrance susceptibility alleles. Previous studies of the BRCA2 N372H polymorphism suggested that HH homozygotes have a modestly increased risk of both breast and ovarian cancer. We have examined whether BRCA2 N372H or common amino acid-changing polymorphisms in BRCA1 predispose to ovarian cancer. A population-based, case control study of ovarian cancer was performed in North Carolina. Cases included 312 women with ovarian cancer (76% invasive and 24% borderline) and 401 age- and race-matched controls. Blood DNA from subjects was genotyped for BRCA2 N372H and BRCA1 Q356R and P871L. There was no association between BRCA2 N372H and risk of borderline or invasive epithelial ovarian cancer. The overall odds ratio (OR) for HH homozygotes was 0.8 [95% confidence interval (CI) = 0.4-1.5] and was similar in all subsets, including invasive serous cases. In addition, neither the BRCA1 Q356R (OR = 0.9, 95% CI 0.5-1.4) nor P871L (OR = 0.9, 95% CI 0.6-1.9) polymorphisms were associated with ovarian cancer risk. There was a significant racial difference in allele frequencies of the P871L polymorphism (P = 0.64 in Caucasians, L = 0.76 in African-Americans, P < 0.0001). In this population-based, case control study, common amino acid changing BRCA1 and 2 polymorphisms were not found to affect the risk of developing ovarian cancer.

Clinical, hormonal, ovarian, and genetic aspects of 46,XX patients with congenital adrenal hyperplasia due to CYP17A1 defects.

PubMed

Carvalho, Luciane Carneiro de; Brito, Vinicius Nahime; Martin, Regina Matsunaga; Zamboni, Aline Machado; Gomes, Larissa Garcia; Inácio, Marlene; Mermejo, Livia Mara; Coeli-Lacchini, Fernanda; Teixeira, Virginia Ribeiro; Gonçalves, Fabrícia Torres; Carrilho, Alexandre José Faria; Del Toro Camargo, Kenny Yelena; Finkielstain, Gabriela Paula; Taboada, Giselle Fernandes; Frade Costa, Elaine Maria; Domenice, Sorahia; Mendonca, Berenice Bilharinho

2016-06-01

To perform a clinical, biochemical, and molecular evaluation of patients with CYP17A1 defects, including ovarian imaging. Retrospective study. Tertiary care center. Sixteen patients with congenital adrenal hyperplasia due to CYP17A1 defects with a median chronological age of 20 years and belonging to 10 unrelated families. None. Clinical and biochemical parameters, molecular diagnosis, ovarian imaging, and therapeutic management. Seventy-one percent of patients presented with primary amenorrhea, 50% had no breast development, and pubic hair was absent or sparse in all patients; 88% had high blood pressure at diagnosis. Basal LH and P levels were high, and androgen levels were low in all patients. Ultrasound revealed ovarian enlargement in 68.7% and ovarian macrocysts in 62.5% of patients before treatment; three patients had a previous surgical correction of ovarian torsion or rupture. Molecular analysis revealed inactivating CYP17A1 mutations in all patients. The most prevalent mutation was p.W406R, and one patient bore a novel p.G478S/p.I223Nfs*10 compound heterozygous mutation. Treatment with dexamethasone, estrogen, and P resulted in reduction of ovarian volume. Amenorrhea, absent/sparse pubic hair, hypertension, and ovarian macrocysts, whichincrease the risk of ovarian torsion, are important elements in the diagnosis of 46,XX patients with CYP17A1 defects. High basal P levels in patients with hypergonadotropic hypogonadism point to the diagnosis of CYP17A1 defects. Fertility can be achieved in these patients with novel reproductive techniques. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Prediction of Poor Ovarian response by Biochemical and Biophysical Markers: A Logistic Regression Model.

PubMed

Jaiswar, S P; Natu, S M; Sujata; Sankhwar, P L; Manjari, Gupta

2015-12-01

To study correlation between ovarian reserve with biophysical markers (antral follicle count and ovarian volume) and biochemical markers (S. FSH, S. Inhibin B, and S. AMH) and use these markers to predict poor ovarian response to ovarian induction. This is a prospective observational study. One hundred infertile women attending the Obst & Gynae Dept, KGMU were recruited. Blood samples were collected on day 2/day 3 for assessment of S. FSH, S. Inhibin B, and S. AMH and TVS were done for antral follicle count and ovarian volume. Clomephene citrate 100 mg 1OD was given from day 2 to 6, and patients were followed up with serial USG measurements. The numbers of dominant follicles (> or = 14 mm) at the time of hCG administration were counted. Patients with <3 follicles in the 1st cycle were subjected to the 2nd cycle of clomephene 100 mg 1OD from day 2 to day 6 with Inj HMG 150 IU given i.m. starting from day 8 and every alternate day until at least one leading follicle attained ≥18 mm. Development of <3 follicles at end of the 2nd cycle was considered as poor response. Univariate analyses showed that s. inhibin B presented the highest (ROCAUC = 0.862) discriminating potential for predicting poor ovarian response, In multivariate logistic regression model, the variables age, FSH, AMH, INHIBIN B, and AFC remained significant, and the resulting model showed a predicted accuracy of 84.4 %. A derived multimarker computation by a logistic regression model for predicting poor ovarian response was obtained through this study. Thus, potential poor responders could be identified easily, and appropriate ovarian stimulation protocol could be devised for such pts.

Adenovirus-mediated truncated Bid overexpression induced by the Cre/LoxP system promotes the cell apoptosis of CD133+ ovarian cancer stem cells.

PubMed

Long, Qifang; Yang, Ru; Lu, Weixian; Zhu, Weipei; Zhou, Jundong; Zheng, Cui; Zhou, Dongmei; Yu, Ling; Wu, Jinchang

2017-01-01

Cancer stem cells are a small subset of cancer cells that contribute to cancer progression, metastasis, chemoresistance and recurrence. CD133-positive (CD133+) ovarian cancer cells have been identified as ovarian cancer stem cells. Adenovirus-mediated gene therapy is an innovative therapeutic method for cancer treatment. In the present study, we aimed to develop a new gene therapy to specifically eliminate CD133+ ovarian cancer stem cells by targeting CD133. We used the Cre/LoxP system to augment the selective expression of the truncated Bid (tBid) gene as suicide gene therapy in CD133+ ovarian cancer stem cells. The adenovirus (Ad)-CD133-Cre expressing Cre recombinase under the control of the CD133 promoter and Ad-CMV-LoxP-Neo-LoxP-tBid expressing tBid under the control of the CMV promoter were successfully constructed using the Cre/LoxP switching system. The co-infection of Ad-CMV-LoxP-Neo-LoxP-tBid and Ad-CD133-Cre selectively induced tBid overexpression, which inhibited cell growth and triggered the cell apoptosis of CD133+ ovarian cancer stem cells. The Cre/LoxP system-mediated tBid overexpression activated the pro-apoptotic signaling pathway and augmented the cytotoxic effect of cisplatin in CD133+ ovarian cancer stem cells. Furthermore, in xenograft experiments, co-infection with the two recombinant adenoviruses markedly suppressed tumor growth in vivo and promoted cell apoptosis in tumor tissues. Taken together, the present study provides evidence that the adenovirus-mediated tBid overexpression induced by the Cre/LoxP system can effectively eliminate CD133+ ovarian cancer stem cells, representing a novel therapeutic strategy for the treatment of ovarian cancer.

Expression and clinical implication of Beclin1, HMGB1, p62, survivin, BRCA1 and ERCC1 in epithelial ovarian tumor tissues.

PubMed

Ju, L-L; Zhao, C Y; Ye, K-F; Yang, H; Zhang, J

2016-05-01

The aim of the present study is to investigate the differential expression of Beclin1, HMGB1, p62, survivin, ERCC1 and BRCA1 protein in epithelial ovarian cancer (EOC) and to evaluate the relationship between autophagy and platinum resistance of EOC patients during platinum-based chemotherapy with the protein expression. Expression of Beclin1, HMGB1, p62, survivin, ERCC1 and BRCA1 were detected with immunohistochemistry in 60 patients, including 39 with epithelial ovarian cancer (EOC), 13 benign epithelial ovarian tumor tissue (BET) and 8 borderline ovarian tumor tissue. Beclin, p62 and ERCC1 expression was significantly higher in the EOC than the BET (p<0.05). No statistical significance was detected with HMGB1 or survivin expression among BET, borderline tumor and EOC (p>0.05). BRCA1 expression was lower in EOC than BET (p<0.05). The expression of Beclin, p62 and survivin significantly correlated with FIGO stage (p<0.05), while the expression of HMGB1 correlated with pathological type. For platinum-sensitive EOC patients, positive expression of Beclin1 and BRCA1 was lower, and positive P62 expression was higher than in platinum-resistant patients (p<0.05). BRCA1 expression was negatively correlated with Beclin1 and p62 expression (p<0.05). Inhibition of expression of beclin1 may suppress autophagy to enhance the efficiency of platinum-sensitive ovarian cancer. HMGB1, survivin and p62 are implicated in the development of ovarian cancer. ERCC1 might be a potential predictive marker for neoadjuvant treatment in the early stage of ovarian cancer, and BRCA1, Beclin1 and p62 as a biomarker to predict platinum resistance and prognosis of epithelial ovarian cancer.

The influence of dietary antioxidant on ovarian eggs and levels of vitamin E, C, A, astaxanthin, β-carotene and oxidative stres in tissues of Astacus leptodactylus (Eschscholtz) during reproduction.

PubMed

Barim-Oz, O; Sahin, H

2016-12-30

The experiment was conducted to determine the most effective antioxidant (among the vitamin E (VE), vitamin C (VC), vitamin A (VA), astaxanthine (AX), β-carotene (βC)) on the ovarian egg number and size, level of VE, VC, VA, AX, βC and oxidative stress (as malondialdehyde (MDA)) in the hepatopancreas, ovarian, gills and muscle tissue during ovarian development of Astacus leptodactylus. One control (C) and five experimental diets (EE, EC, EA, EAX and EβC) were prepared. The EE, EC, EA, EAX and EβC groups were formed by added 150 mg kg-1 VE, 200 mg kg-1 VC, 240 mg kg-1 VA, 200 mg kg-1 AX and 200 mg kg-1 βC to diet C, respectively. At the end of the experiment found that the dietary antioxidants increased ovarian egg number and size and reduced the level of MDA in the tissues. Ovarian egg number and size were highest in the EE and EAX diet groups in the comparison to control (p<0.001). The level of MDA in the tissues was lowest in the EAX diet group in the comparison to control (p<0.001). The highest levels of VE, VC, VA, AX and βC were found in the hepatopancreas and ovarian compared with muscle and gills. The highest level of MDA also was determined in the ovarian according to other tissues. In conclusion, the VE and AX in broodstock diets were the most effective antioxidants on the ovarian egg number and size of A. leptodactylus.

Cigarette smoking is associated with adverse survival among women with ovarian cancer: Results from a pooled analysis of 19 studies

PubMed Central

Præstegaard, Camilla; Jensen, Allan; Jensen, Signe M.; Nielsen, Thor S. S.; Webb, Penelope M.; Nagle, Christina M.; DeFazio, Anna; Høgdall, Estrid; Rossing, Mary Anne; Doherty, Jennifer A.; Wicklund, Kristine G.; Goodman, Marc T.; Modugno, Francesmary; Moysich, Kirsten; Ness, Roberta B.; Edwards, Robert; Matsuo, Keitaro; Hosono, Satoyo; Goode, Ellen L.; Winham, Stacey J; Fridley, Brooke L.; Cramer, Daniel W.; Terry, Kathryn L.; Schildkraut, Joellen M.; Berchuck, Andrew; Bandera, Elisa V.; Paddock, Lisa E.; Massuger, Leon F.; Wentzensen, Nicolas; Pharoah, Paul; Song, Honglin; Whittemore, Alice; McGuire, Valerie; Sieh, Weiva; Rothstein, Joseph; Anton-Culver, Hoda; Ziogas, Argyrios; Menon, Usha; Gayther, Simon A.; Ramus, Susan J.; Gentry-Maharaj, Alexandra; Wu, Anna H.; Pearce, Celeste L.; Pike, Malcolm; Lee, Alice W.; Sutphen, Rebecca; Chang-Claude, Jenny; Risch, Harvey A.; Kjaer, Susanne K.

2017-01-01

Cigarette smoking is associated with an increased risk of developing mucinous ovarian tumors but whether it is associated with ovarian cancer survival overall or for the different histotypes is unestablished. Furthermore, it is unknown whether the association between cigarette smoking and survival differs according to strata of ovarian cancer stage at diagnosis. In a large pooled analysis, we evaluated the association between various measures of cigarette smoking and survival among women with epithelial ovarian cancer. We obtained data from 19 case-control studies in the Ovarian Cancer Association Consortium (OCAC), including 9,114 women diagnosed with ovarian cancer. Cox regression models were used to estimate adjusted study-specific hazard ratios (HRs), which were combined into pooled hazard ratios (pHR) with corresponding 95% confidence intervals (CIs) under random effects models. Overall, 5,149 (57%) women died during a median follow-up period of 7.0 years. Among women diagnosed with ovarian cancer, both current (pHR = 1.17, 95% CI: 1.08–1.28) and former smokers (pHR = 1.10, 95% CI: 1.02–1.18) had worse survival compared with never smoking women. In histotype-stratified analyses, associations were observed for mucinous (current smoking: pHR = 1.91, 95% CI: 1.01–3.65) and serous histotypes (current smoking: pHR = 1.11, 95% CI: 1.00–1.23; former smoking: pHR = 1.12, 95% CI: 1.04–1.20). Further, our results suggested that current smoking has a greater impact on survival among women with localized than disseminated disease. The identification of cigarette smoking as a modifiable factor associated with survival has potential clinical importance as a focus area to improve ovarian cancer prognosis. PMID:28063166

DYNAMIC BEHAVIOR OF A DELAY-DIFFERENTIAL EQUATION MODEL FOR THE HORMONAL REGULATION OF THE MENSTRUAL CYCLE

EPA Science Inventory

During the menstrual cycle, pituitary hormones stimulate the growth and development of ovarian follicles and the release of an ovum to be fertilized. The ovarian follicles secrete hormones during the cycle that regulate the production of the pituitary hormones creating positi...

Reduced energy expenditure and increased inflammation are early events in the development of ovariectomy-induced obesity

USDA-ARS?s Scientific Manuscript database

Menopause, an age-related loss of ovarian hormone production, promotes increased adiposity and associated metabolic pathologies. However, the diet-independent mechanism(s) by which loss of ovarian function promotes increased adipose tissue mass and insulin resistance remain unclear. We investigate...

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

DTIC Science & Technology

2015-07-01

development of epithelial ovarian cancer. Neoplasia 2011, 13: 393-405 3). Hanahan, D, Coussens, LM: Accessories to the crime : functions of cells recruited...α10 subunit: expression pattern, partial gene structure, and chromosomal localization. Cytogent Cell Genet 1998, 87: 238-244 40   29   47

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

ClinicalTrials.gov

2017-09-27

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

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

PubMed Central

Virant-Klun, Irma; Stimpfel, Martin

2016-01-01

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

Primary Ovarian Insufficiency: X chromosome defects and autoimmunity.

PubMed

Persani, Luca; Rossetti, Raffaella; Cacciatore, Chiara; Bonomi, Marco

2009-08-01

Premature ovarian failure (POF) is a primary ovarian defect characterized by absent menarche or premature depletion of ovarian follicles before the age of 40 years. However, in several instances the distinction between definitive or intermittent POF may be difficult on clinical bases, therefore the more appropriate term Primary Ovarian Insufficiency (POI) has been recently proposed and will be used in this review. POI is a heterogeneous disorder affecting approximately 1% of women <40 years. The most severe forms present with absent pubertal development and primary amenorrhea, whereas forms with post-pubertal onset are characterized by disappearance of menstrual cycles (secondary amenorrhea) associated with a defective folliculogenesis. POI is generally characterized by low levels of gonadal hormones (estrogens and inhibins) and high levels of gonadotropins (LH and FSH) (hypergonadotropic amenorrhea). Heterogeneity of POI is reflected by the variety of possible causes, including autoimmunity, toxics, drugs, as well as genetic defects. Several data indicate that POI has a strong genetic component. In this manuscript we discuss the X chromosome abnormalities that are associated with POI.

Altered ovarian function affects skeletal homeostasis independent of the action of follicle-stimulating hormone.

PubMed

Gao, Jianjun; Tiwari-Pandey, Rashmi; Samadfam, Rana; Yang, Yinzhi; Miao, Dengshun; Karaplis, Andrew C; Sairam, M Ram; Goltzman, David

2007-06-01

Osteoporosis is a leading public health problem. Although a major cause in women is thought to be a decline in estrogen, it has recently been proposed that FSH or follitropin is required for osteoporotic bone loss. We examined the FSH receptor null mouse (FORKO mouse) to determine whether altered ovarian function could induce bone loss independent of FSH action. By 3 months of age, FORKO mice developed age-dependent declines in bone mineral density and trabecular bone volume of the lumbar spine and femur, which could be partly reversed by ovarian transplantation. Bilateral ovariectomy reduced elevated circulating testosterone levels in FORKO mice and decreased bone mass to levels indistinguishable from those in ovariectomized wild-type controls. Androgen receptor blockade and especially aromatase inhibition each produced bone volume reductions in the FORKO mouse. The results indicate that ovarian secretory products, notably estrogen, and peripheral conversion of ovarian androgen to estrogen can alter bone homeostasis independent of any bone resorptive action of FSH.

A Rare Case of De Novo Gigantic Ovarian Abscess within an Endometrioma

PubMed Central

Hameed, Aisha; Mehta, Vaishali; Sinha, Prabha

2010-01-01

We are reporting a rare case of de novo ovarian abscess in an endometrioma. Ovarian abscess within an endometrioma is a rare gynecological problem, but de novo abscess in the endometrioma is even rarer. Most of the ovarian abscesses develop in the endometriomas following interventions, e.g., aspiration, pelvic surgery, and oocyte retrieval. We are presenting a case of a spontaneous giant abscess in a large ovarian cyst in a nulliparous woman who presented with acute abdomen. Patient was treated in a district general hospital with multidisciplinary approach. Thirteen liters of the pus were drained. She has had a sub total (supra cervical) hysterectomy and bilateral salpingo-oophorectomy (BSO) performed. Histology of the abscess wall confirmed endometriotic nature of the cyst. Patient made an uneventful recovery and was discharged home on the 14th postoperative day. This case highlights that endometrioma and its complication can present as a surgical emergency and should be dealt as one. PMID:20589187

Amygdala Kindling Alters Estrus Cycle and Ovarian Morphology in the Rat.

PubMed

Pan, Juan; Zhang, Lingwu; Wang, Feng; Liu, Dan; Li, P Andy; Sun, Tao

2013-11-01

The objective of this study is to explore the effects of amygdala kindling on estrus cycle and ovarian morphology. Thirty-five female rats at the age of 8 weeks were randomly designated to electrode kindled, sham-kindled, and normal controls. Kindled rats were implanted with kindling electrodes in the left basolateral amygdala and kindled by brief suprathreshold stimulations with a bipolar electrode. Estrous cycles were daily monitored through vaginal smears. Electrographic and behavioral seizures were recorded and ovarian morphology was evaluated by light and electron microscopies. Our results showed that the kindled rats lost their ovarian periodicity displayed significant ovarian enlargement. H&E staining revealed increased number of growing follicles and total follicles, as well as polycysts in the ovaries of the kindled animals compared to sham and control animals. Ultrastructural study detected numerous apoptotic granulosa cells in growing follicles and thecal cell hyperplasia with secretary granules in the thecal cells in the kindled rats. The results suggest that amygdala kindling is a risk factor for the development of polycystic ovary syndrome.

A rare case of de novo gigantic ovarian abscess within an endometrioma.

PubMed

Hameed, Aisha; Mehta, Vaishali; Sinha, Prabha

2010-06-01

We are reporting a rare case of de novo ovarian abscess in an endometrioma. Ovarian abscess within an endometrioma is a rare gynecological problem, but de novo abscess in the endometrioma is even rarer. Most of the ovarian abscesses develop in the endometriomas following interventions, e.g., aspiration, pelvic surgery, and oocyte retrieval. We are presenting a case of a spontaneous giant abscess in a large ovarian cyst in a nulliparous woman who presented with acute abdomen. Patient was treated in a district general hospital with multidisciplinary approach. Thirteen liters of the pus were drained. She has had a sub total (supra cervical) hysterectomy and bilateral salpingo-oophorectomy (BSO) performed. Histology of the abscess wall confirmed endometriotic nature of the cyst. Patient made an uneventful recovery and was discharged home on the 14th postoperative day. This case highlights that endometrioma and its complication can present as a surgical emergency and should be dealt as one.

Bevacizumab and Intravenous or Intraperitoneal Chemotherapy in Treating Patients With Stage II-III Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer

ClinicalTrials.gov

2018-05-25

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

BAD-mediated apoptotic pathway is associated with human cancer development.

PubMed

Stickles, Xiaomang B; Marchion, Douglas C; Bicaku, Elona; Al Sawah, Entidhar; Abbasi, Forough; Xiong, Yin; Bou Zgheib, Nadim; Boac, Bernadette M; Orr, Brian C; Judson, Patricia L; Berry, Amy; Hakam, Ardeshir; Wenham, Robert M; Apte, Sachin M; Berglund, Anders E; Lancaster, Johnathan M

2015-04-01

The malignant transformation of normal cells is caused in part by aberrant gene expression disrupting the regulation of cell proliferation, apoptosis, senescence and DNA repair. Evidence suggests that the Bcl-2 antagonist of cell death (BAD)-mediated apoptotic pathway influences cancer chemoresistance. In the present study, we explored the role of the BAD-mediated apoptotic pathway in the development and progression of cancer. Using principal component analysis to derive a numeric score representing pathway expression, we evaluated clinico-genomic datasets (n=427) from corresponding normal, pre-invasive and invasive cancers of different types, such as ovarian, endometrial, breast and colon cancers in order to determine the associations between the BAD-mediated apoptotic pathway and cancer development. Immunofluorescence was used to compare the expression levels of phosphorylated BAD [pBAD (serine-112, -136 and -155)] in immortalized normal and invasive ovarian, colon and breast cancer cells. The expression of the BAD-mediated apoptotic pathway phosphatase, PP2C, was evaluated by RT-qPCR in the normal and ovarian cancer tissue samples. The growth-promoting effects of pBAD protein levels in the immortalized normal and cancer cells were assessed using siRNA depletion experiments with MTS assays. The expression of the BAD-mediated apoptotic pathway was associated with the development and/or progression of ovarian (n=106, p<0.001), breast (n=185, p<0.0008; n=61, p=0.04), colon (n=22, p<0.001) and endometrial (n=33, p<0.001) cancers, as well as with ovarian endometriosis (n=20, p<0.001). Higher pBAD protein levels were observed in the cancer cells compared to the immortalized normal cells, whereas PP2C gene expression was lower in the cancer compared to the ovarian tumor tissue samples (n=76, p<0.001). The increased pBAD protein levels after the depletion of PP2C conferred a growth advantage to the immortalized normal and cancer cells. The BAD-mediated apoptotic pathway is thus associated with the development of human cancers likely influenced by the protein levels of pBAD.

Benefits of nanoencapsulation for the hypercin-mediated photodetection of ovarian micrometastases.

PubMed

Zeisser-Labouèbe, Magali; Delie, Florence; Gurny, Robert; Lange, Norbert

2009-02-01

The high recurrence and lethality of ovarian cancer at advanced stages is problematic, especially due to the development of numerous micrometastases scattered throughout the abdominal cavity. Fluorescence photodetection (PD) used in combination with surgical resection of malignant tissues has been suggested to improve recovery. Based on promising in vivo results for the detection of bladder cancer, hypericin (Hy), a natural photosensitizer (PS), stands as a good candidate for the photodetection of ovarian cancer. However, due to its hydrophobicity, systemic administration of Hy is problematic. Polymeric nanoparticles (NPs) help to overcome these delivery and stability problems and enable intravenous administration of Hy. In this study, Hy-loaded NPs of polylactic acid were produced with the following properties: (i) mean size of 268 nm, (ii) negative zeta potential, (iii) low residual surfactant and (iv) drug loading of 3.7 % (w/w). The potential of hypericin-loaded nanoparticles for the fluorescence photodetection of ovarian metastases in Fischer 344 rats bearing ovarian tumours was compared to free drug. The selectivity of Hy administered with both formulations was assessed first by fluorescence endoscopy, and then quantified after tissue extraction. The results showed an improved selective accumulation of Hy in ovarian micrometastases when NPs were used.

Coregistered three-dimensional ultrasound and photoacoustic imaging system for ovarian tissue characterization

PubMed Central

Aguirre, Andres; Guo, Puyun; Gamelin, John; Yan, Shikui; Sanders, Mary M.; Brewer, Molly; Zhu, Quing

2009-01-01

Ovarian cancer has the highest mortality of all gynecologic cancers, with a five-year survival rate of only 30% or less. Current imaging techniques are limited in sensitivity and specificity in detecting early stage ovarian cancer prior to its widespread metastasis. New imaging techniques that can provide functional and molecular contrasts are needed to reduce the high mortality of this disease. One such promising technique is photoacoustic imaging. We develop a 1280-element coregistered 3-D ultrasound and photoacoustic imaging system based on a 1.75-D acoustic array. Volumetric images over a scan range of 80 deg in azimuth and 20 deg in elevation can be achieved in minutes. The system has been used to image normal porcine ovarian tissue. This is an important step toward better understanding of ovarian cancer optical properties obtained with photoacoustic techniques. To the best of our knowledge, such data are not available in the literature. We present characterization measurements of the system and compare coregistered ultrasound and photoacoustic images of ovarian tissue to histological images. The results show excellent coregistration of ultrasound and photoacoustic images. Strong optical absorption from vasculature, especially highly vascularized corpora lutea and low absorption from follicles, is demonstrated. PMID:19895116

Alginate: A Versatile Biomaterial to Encapsulate Isolated Ovarian Follicles.

PubMed

Vanacker, Julie; Amorim, Christiani A

2017-07-01

In vitro culture of ovarian follicles isolated or enclosed in ovarian tissue fragments and grafting of isolated ovarian follicles represent a potential alternative to restore fertility in cancer patients who cannot undergo cryopreservation of embryos or oocytes or transplantation of frozen-thawed ovarian tissue. In this regard, respecting the three-dimensional (3D) architecture of isolated follicles is crucial to maintaining their proper follicular physiology. To this end, alginate hydrogel has been widely investigated using follicles from numerous animal species, yielding promising results. The goal of this review is therefore to provide an overview of alginate applications utilizing the biomaterial as a scaffold for 3D encapsulation of isolated ovarian follicles. Different methods of isolated follicle encapsulation in alginate are discussed in this review, as its use of 3D alginate culture systems as a tool for in vitro follicle analysis. Possible improvements of this matrix, namely modification with arginine-glycine-aspartic acid peptide or combination with fibrin, are also summarized. Encouraging results have been obtained in different animal models, and particularly with isolated follicles encapsulated in alginate matrices and grafted to mice. This summary is designed to guide the reader towards development of next-generation alginate scaffolds, with enhanced properties for follicle encapsulation.

Dual ovarian stimulation and random start in assisted reproductive technologies: from ovarian biology to clinical application.

PubMed

Vaiarelli, Alberto; Venturella, Roberta; Vizziello, Damiano; Bulletti, Francesco; Ubaldi, Filippo M

2017-06-01

The opportunity to use gonadotropins to stimulate the growth of antral follicles coming from different follicular waves available in different moment of the menstrual cycle allowed the implementation of innovative protocols in assisted reproductive technologies. The purpose of this review is to explore the possible advantages related to these new controlled ovarian stimulation (COS) strategies. Women exhibit major and minor wave patterns of ovarian follicular development during the menstrual cycle, as it is in animal species. These observations led to the introduction of two new strategies for COS: the random start and the double ovarian stimulation within a single menstrual cycle. The use of gonadotropin-releasing hormone antagonist COS protocols, started randomly at any day of the menstrual cycle, is today a standard procedure in those cases where obtaining oocytes is an urgent task, such as in case of fertility preservation for malignant diseases or other medical indications.On the other hand, in poor prognosis patients, double ovarian stimulation has been suggested with the aim of maximizing the number of oocytes retrieved within a single menstrual cycle and, in turn increasing the chance to obtain a reproductively competent embryo. Randomized control trials are necessary to confirm these preliminary findings.

Testing for NRAS Mutations in Serous Borderline Ovarian Tumors and Low-Grade Serous Ovarian Carcinomas

PubMed Central

Grzanka, Dariusz; Grabiec, Marek

2018-01-01

The Idylla NRAS Mutation Test, performed on the Biocartis Idylla system, is an in vitro diagnostic tool for the qualitative assessment of 18 NRAS mutations in codons 12, 13, 59, 61, 117, and 146. Low-grade serous ovarian cancer (LGSC) represents less than 10% of all serous ovarian carcinomas. LGSCs are believed to arise from preexisting cystadenomas or serous borderline tumors (SBOTs) that eventually progress to an invasive carcinoma. The molecular analysis of cancer-causing mutations and the development of targeted biological therapies constitute a milestone in the diagnosis and therapy of ovarian malignancies. According to some authors, NRAS may be an important oncogene for the progression of SBOT to a frankly invasive disease. The primary aim of this study was to verify if a fully integrated, real-time PCR-based Idylla system can be used for the rapid determination of the NRAS mutation status in patients with serous borderline ovarian tumors and low-grade serous ovarian carcinomas. The study included tissue specimens from 12 patients with histopathologically verified ovarian masses, operated on at the Department of Obstetrics and Gynecology, Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz (Poland), between January 2009 and June 2012. The mean age of the study patients was 52.5 years (range 27–80 years). NRAS mutation in codon 13 (G13D, p.Gly13Asp; nucleotide: c.38G>A) was found in one patient, a woman with low-grade serous ovarian carcinoma. To the best of our knowledge, our experiment was the first published study using the novel Idylla NRAS Mutation Test for the evaluation of ovarian tumors in a clinical setting. The Idylla platform is an interesting ancillary first-line rapid and fully automated instrument to detect NRAS mutations in SBOTs and LGSCs. However, the clinical usefulness of this method still needs to be verified in larger groups of cancer patients. PMID:29682098

Long-term survival in pseudo-Meigs' syndrome caused by ovarian metastases from colon cancer.

PubMed

Tajima, Yosuke; Kameyama, Hitoshi; Yamada, Saki; Yagi, Ryoma; Nakano, Masato; Nagahashi, Masayuki; Shimada, Yoshifumi; Sakata, Jun; Kobayashi, Takashi; Umezu, Hajime; Wakai, Toshifumi

2016-11-14

Meigs' syndrome is defined as the co-existence of benign ovarian fibroma or fibroma-like tumor, ascites, and pleural effusion. In contrast, pseudo-Meigs' syndrome is defined as the co-existence of other ovarian or pelvic tumors, ascites, and pleural effusion. In Meigs' and pseudo-Meigs' syndromes, ascites and pleural effusion resolve promptly after the complete resection of the ovarian or pelvic tumor(s). Secondary ovarian tumors from colorectal gastrointestinal metastases rarely cause pseudo-Meigs' syndrome; only 11 cases of pseudo-Meigs' syndrome secondary to colorectal cancers have been reported in the literature. Therefore, the prognosis and etiology of pseudo-Meigs' syndrome caused by ovarian metastasis from colorectal cancers remain unclear. We report here a rare case of pseudo-Meigs' syndrome caused by ovarian metastases from sigmoid colon cancer with long-term survival. A 47-year-old woman presented with abdominal distention of 1-month duration. She developed acute dyspnea 2 weeks after the initial presentation. Colonoscopy and computed tomography revealed sigmoid colon cancer with an ovarian metastasis, along with massive ascites and bilateral pleural effusion. Emergency operation, including bilateral oophorectomy and sigmoidectomy, was performed. Subsequently, ascites and bilateral pleural effusion resolved rapidly. Curative hepatic resection was performed for liver metastases 29 months after the first operation, and as of this writing, the patient is alive with no evidence of a disease 78 months after the first operation. In general, colorectal cancer with ovarian metastasis is hard to cure, and long-term survival in patients with colorectal cancer with pseudo-Meigs' syndrome is rare. Our experience suggests that curative resection for pseudo-Meigs' syndrome caused by ovarian metastasis from colorectal cancer may offer long-term survival. Our experience suggests that pseudo-Meigs' syndrome can occur in a patient with colorectal cancer after metastasis to the ovaries, causing massive ascites and pleural effusion. Aggressive treatment, including R0 resection, for this disease if allowed by the patient's general condition may offer long-term survival.

Towards an animal model of ovarian cancer: cataloging chicken blood proteins using combinatorial peptide ligand libraries coupled with shotgun proteomic analysis for translational research.

PubMed

Ma, Yingying; Sun, Zeyu; de Matos, Ricardo; Zhang, Jing; Odunsi, Kunle; Lin, Biaoyang

2014-05-01

Epithelial ovarian cancer is the most deadly gynecological cancer around the world, with high morbidity in industrialized countries. Early diagnosis is key in reducing its morbidity rate. Yet, robust biomarkers, diagnostics, and animal models are still limited for ovarian cancer. This calls for broader omics and systems science oriented diagnostics strategies. In this vein, the domestic chicken has been used as an ovarian cancer animal model, owing to its high rate of developing spontaneous epithelial ovarian tumors. Chicken blood has thus been considered a surrogate reservoir from which cancer biomarkers can be identified. However, the presence of highly abundant proteins in chicken blood has compromised the applicability of proteomics tools to study chicken blood owing to a lack of immunodepletion methods. Here, we demonstrate that a combinatorial peptide ligand library (CPLL) can efficiently remove highly abundant proteins from chicken blood samples, consequently doubling the number of identified proteins. Using an integrated CPLL-1DGE-LC-MSMS workflow, we identified a catalog of 264 unique proteins. Functional analyses further suggested that most proteins were coagulation and complement factors, blood transport and binding proteins, immune- and defense-related proteins, proteases, protease inhibitors, cellular enzymes, or cell structure and adhesion proteins. Semiquantitative spectral counting analysis identified 10 potential biomarkers from the present chicken ovarian cancer model. Additionally, many human homologs of chicken blood proteins we have identified have been independently suggested as diagnostic biomarkers for ovarian cancer, further triangulating our novel observations reported here. In conclusion, the CPLL-assisted proteomic workflow using the chicken ovarian cancer model provides a feasible platform for translational research to identify ovarian cancer biomarkers and understand ovarian cancer biology. To the best of our knowledge, we report here the most comprehensive survey of the chicken blood proteome to date.

PTN Signaling: Components and Mechanistic Insights in Human Ovarian Cancer

PubMed Central

Sethi, Geetika; Kwon, Youngjoo; Burkhalter, Rebecca J; Pathak, Harsh B.; Madan, Rashna; McHugh, Sarah; Atay, Safinur; Murthy, Smruthi; Tawfik, Ossama W.; Godwin, Andrew K.

2015-01-01

Molecular vulnerabilities represent promising candidates for the development of targeted therapies that hold the promise to overcome the challenges encountered with non-targeted chemotherapy for the treatment of ovarian cancer. Through a synthetic lethality screen, we previously identified pleiotrophin (PTN) as a molecular vulnerability in ovarian cancer and showed that siRNA mediated PTN knockdown induced apoptotic cell death in epithelial ovarian cancer (EOC) cells. Although it is well known that PTN elicits its pro-tumorigenic effects through its receptor, protein tyrosine phosphatase receptor Z1 (PTPRZ1), little is known about the potential importance of this pathway in the pathogenesis of ovarian cancer. In this study we show that PTN is expressed, produced, and secreted in a panel of EOC cell lines. PTN levels in serous ovarian tumor tissues are on average 3.5-fold higher relative to normal tissue and PTN is detectable in serum samples of patients with EOC. PTPRZ1 is also expressed and produced by EOC cells and is found to be up-regulated in serous ovarian tumor tissue relative to normal ovarian surface epithelial tissue (p<0.05). Gene silencing of PTPRZ1 in EOC cell lines using siRNA mediated knockdown shows that PTPRZ1 is essential for viability and results in significant apoptosis with no effect on the cell cycle phase distribution. In order to determine how PTN mediates survival, we silenced the gene using siRNA mediated knockdown and performed expression profiling of 36 survival-related genes. Through computational mapping of the differentially expressed genes, members of the MAPK (mitogen-activated protein kinase) family were found to be likely effectors of PTN signaling in EOC cells. Our results provide the first experimental evidence that PTN and its signaling components may be of significance in the pathogenesis of epithelial ovarian cancer and provide a rationale for clinical evaluation of MAPK inhibitors in PTN and/or PTPRZ1 expressing ovarian tumors. PMID:25418856

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

Freezing oocytes or embryos after controlled ovarian hyperstimulation in cancer patients: the state of the art.

PubMed

Bénard, Julie; Duros, Solène; El Hachem, Hady; Sonigo, Charlotte; Sifer, Christophe; Grynberg, Michaël

2016-07-01

Quality of life of young cancer survivors has become a major issue. However, anticancer therapies can have a detrimental impact on fertility. It is now well-established that all patients should receive information about the fertility risks associated with their cancer treatment and the fertility preservation options available. Currently, oocyte or embryo banking after controlled ovarian hyperstimulation represents the most effective method for preserving female fertility. Over the past years innovative protocols of ovarian stimulation have been developed to enable cancer patients to undergo oocyte or embryo cryopreservation irrespective of the phase of the cycle or without exogenous follicle-stimulating hormone-related increase in serum estradiol levels. The present article reviews the different protocols of ovarian hyperstimulation for cancer patients, candidates for fertility preservation.

Evolution of platinum resistance in high-grade serous ovarian cancer.

PubMed

Cooke, Susanna L; Brenton, James D

2011-11-01

High-grade serous ovarian cancers account for most ovarian-cancer mortality. Although this disease initially responds well to platinum-based chemotherapy, relapse and progression to chemotherapy resistance are frequently seen. Time to relapse after first-line therapy is a predictor of response to secondary platinum treatment: more than 12 months is associated with high chance of a secondary response, whereas relapses within 6 months generally indicate platinum resistance. In this Personal View we discuss whether patterns of response, relapse, and the development of drug resistance in high-grade serous ovarian cancers are related to distinct underlying molecular and cellular biological characteristics. In particular, we propose that rapid relapse with platinum-resistant disease is due to minor subpopulations of intrinsically resistant cancer cells at presentation. Copyright © 2011 Elsevier Ltd. All rights reserved.

Development and Validation of a Protein Based Signature for the Detection of Ovarian Cancer

PubMed Central

Kim, Kyongjin; Visintin, Irene; Alvero, Ayesha B.; Mor, Gil

2009-01-01

In order to overcome the significant mortality associated with ovarian cancer, a highly sensitive and specific screening test is urgently needed. CA125 is used to monitor response to chemotherapy, detect recurrence and detect late stage ovarian cancer. However, CA-125 alone or in combination with ultrasonography has not been adequate for early detection of ovarian cancer. Here we discuss our recent report of a novel multiplex assay that uses a panel of six serum biomarkers:Leptin, Prolactin, Osteopontin, Insulin-Like Growth Factor II, Macrophage Inhibitory Factor and CA-125. The combination of these six proteins yielded 95.3 % sensitivity and 99.4% specificity. The application of this test in the clinical context and the most appropriate population which could benefit of the test is discussed. PMID:19389550

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

ClinicalTrials.gov

2018-04-17

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

Epigenetic modification of α-N-acetylgalactosaminidase enhances cisplatin resistance in ovarian cancer

PubMed Central

Ha, Ye-Na; Sung, Hye Youn; Yang, San-Duk; Chae, Yun Ju

2018-01-01

Although cisplatin is one of the most effective antitumor drugs for ovarian cancer, the emergence of chemoresistance to cisplatin in over 80% of initially responsive patients is a major barrier to successful therapy. The precise mechanisms underlying the development of cisplatin resistance are not fully understood, but alteration of DNA methylation associated with aberrant gene silencing may play a role. To identify epigenetically regulated genes directly associated with ovarian cancer cisplatin resistance, we compared the expression and methylation profiles of cisplatin-sensitive and -resistant human ovarian cancer cell lines. We identified α-Nacetylgalactosaminidase (NAGA) as one of the key candidate genes for cisplatin drug response. Interestingly, in cisplatin-resistant cell lines, NAGA was significantly downregulated and hypermethylated at a promoter CpG site at position +251 relative to the transcriptional start site. Low NAGA expression in cisplatin-resistant cell lines was restored by treatment with a DNA demethylation agent, indicating transcriptional silencing by hyper-DNA methylation. Furthermore, overexpression of NAGA in cisplatin-resistant lines induced cytotoxicity in response to cisplatin, whereas depletion of NAGA expression increased cisplatin chemoresistance, suggesting an essential role of NAGA in sensitizing ovarian cells to cisplatin. These findings indicate that NAGA acts as a cisplatin sensitizer and its gene silencing by hypermethylation confers resistance to cisplatin in ovarian cancer. Therefore, we suggest NAGA may be a promising potential therapeutic target for improvement of sensitivity to cisplatin in ovarian cancer. PMID:29302211

Mechanisms of Cables 1 gene inactivation in human ovarian cancer development.

PubMed

Sakamoto, Hideo; Friel, Anne M; Wood, Antony W; Guo, Lankai; Ilic, Ana; Seiden, Michael V; Chung, Daniel C; Lynch, Maureen P; Serikawa, Takehiro; Munro, Elizabeth; Oliva, Esther; Orsulic, Sandra; Kirley, Sandra D; Foster, Rosemary; Zukerberg, Lawrence R; Rueda, Bo R

2008-02-01

Cables 1, a cyclin-dependent kinase binding protein, is primarily involved in cell cycle regulation. Loss of nuclear Cables 1 expression is observed in human colon, lung and endometrial cancers. We previously reported that loss of nuclear Cables 1 expression was also observed with high frequency in a limited sample set of human ovarian carcinomas, although the mechanisms underlying loss of nuclear Cables 1 expression remained unknown. Our present objective was to examine Cables 1 expression in ovarian cancer in greater detail, and determine the predominant mechanisms of Cables 1 loss. We assessed potential genetic and epigenetic modifications of the Cables 1 locus through analyses of mutation, polymorphisms, loss of heterozygosity and DNA methylation. We observed a marked loss of nuclear Cables 1 expression in serous and endometrioid ovarian carcinomas that correlated with decreased Cables 1 mRNA levels. Although we detected no Cables 1 mutations, there was evidence of LOH at the Cables 1 locus and epigenetic modification of the Cables 1 promoter region in a subset of ovarian carcinomas and established cancer cell lines. From a functional perspective, over-expression of Cables 1 induced apoptosis, whereas, knockdown of Cables 1 negated this effect. Together these findings suggest that multiple mechanisms underlie the loss of Cables 1 expression in ovarian cancer cells, supporting the hypothesis that Cables 1 is a tumor suppressor in human ovarian cancer.

Epigenetic modification of α-N-acetylgalactosaminidase enhances cisplatin resistance in ovarian cancer.

PubMed

Ha, Ye-Na; Sung, Hye Youn; Yang, San-Duk; Chae, Yun Ju; Ju, Woong; Ahn, Jung-Hyuck

2018-01-01

Although cisplatin is one of the most effective antitumor drugs for ovarian cancer, the emergence of chemoresistance to cisplatin in over 80% of initially responsive patients is a major barrier to successful therapy. The precise mechanisms underlying the development of cisplatin resistance are not fully understood, but alteration of DNA methylation associated with aberrant gene silencing may play a role. To identify epigenetically regulated genes directly associated with ovarian cancer cisplatin resistance, we compared the expression and methylation profiles of cisplatin-sensitive and -resistant human ovarian cancer cell lines. We identified α- N acetylgalactosaminidase ( NAGA ) as one of the key candidate genes for cisplatin drug response. Interestingly, in cisplatin-resistant cell lines, NAGA was significantly downregulated and hypermethylated at a promoter CpG site at position +251 relative to the transcriptional start site. Low NAGA expression in cisplatin-resistant cell lines was restored by treatment with a DNA demethylation agent, indicating transcriptional silencing by hyper-DNA methylation. Furthermore, overexpression of NAGA in cisplatin-resistant lines induced cytotoxicity in response to cisplatin, whereas depletion of NAGA expression increased cisplatin chemoresistance, suggesting an essential role of NAGA in sensitizing ovarian cells to cisplatin. These findings indicate that NAGA acts as a cisplatin sensitizer and its gene silencing by hypermethylation confers resistance to cisplatin in ovarian cancer. Therefore, we suggest NAGA may be a promising potential therapeutic target for improvement of sensitivity to cisplatin in ovarian cancer.

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

Sargramostim and Paclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Patients With Advanced Ovarian Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer That Did Not Respond to Previous Chemotherapy

ClinicalTrials.gov

2017-07-24

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; Peritoneal Cavity Cancer; Recurrent Ovarian Epithelial Cancer; Stage III Ovarian Epithelial Cancer; Stage IV Ovarian Epithelial Cancer

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

ClinicalTrials.gov

2017-08-08

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

Pharyngeal cavity and the gills are the target organ for the repellent action of pardaxin in shark.

PubMed

Primor, N

1985-05-15

Pardaxin, an active principle of the repellent secretion of the Red Sea flatfish, Pardachirus marmoratus, elicited severe struggling, mouth paralysis, and transient increase in urea leakage from the gills only when administered to the medium bathing the shark's pharyngeal cavity and gills. An apparatus was constructed which prevents a mixing of the outflow from shark's gills with water bathing its surface skin. It is concluded that in sharks the gills and/or the pharyngeal cavity are the target organ for the repellent action of pardaxin.

The prognostic significance of specific HOX gene expression patterns in ovarian cancer.

PubMed

Kelly, Zoe; Moller-Levet, Carla; McGrath, Sophie; Butler-Manuel, Simon; Kavitha Madhuri, Thumuluru; Kierzek, Andrzej M; Pandha, Hardev; Morgan, Richard; Michael, Agnieszka

2016-10-01

HOX genes are vital for all aspects of mammalian growth and differentiation, and their dysregulated expression is related to ovarian carcinogenesis. The aim of the current study was to establish the prognostic value of HOX dysregulation as well as its role in platinum resistance. The potential to target HOX proteins through the HOX/PBX interaction was also explored in the context of platinum resistance. HOX gene expression was determined in ovarian cancer cell lines and primary EOCs by QPCR, and compared to expression in normal ovarian epithelium and fallopian tube tissue samples. Statistical analysis included one-way ANOVA and t-tests, using statistical software R and GraphPad. The analysis identified 36 of the 39 HOX genes as being overexpressed in high grade serous EOC compared to normal tissue. We detected a molecular HOX gene-signature that predicted poor outcome. Overexpression of HOXB4 and HOXB9 was identified in high grade serous cell lines after platinum resistance developed. Targeting the HOX/PBX dimer with the HXR9 peptide enhanced the cytotoxicity of cisplatin in platinum-resistant ovarian cancer. In conclusion, this study has shown the HOX genes are highly dysregulated in ovarian cancer with high expression of HOXA13, B6, C13, D1 and D13 being predictive of poor clinical outcome. Targeting the HOX/PBX dimer in platinum-resistant cancer represents a potentially new therapeutic option that should be further developed and tested in clinical trials. © 2016 The Authors International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

Characterization of inhibin forms and their measurement by an inhibin alpha-subunit ELISA in serum from postmenopausal women with ovarian cancer.

PubMed

Robertson, D M; Stephenson, T; Pruysers, E; McCloud, P; Tsigos, A; Groome, N; Mamers, P; Burger, H G

2002-02-01

The aim of this study was to characterize the molecular wt forms of inhibins A and B and its free alpha-subunit present in serum from women with ovarian cancer as a basis for developing improved monoclonal antibody-based inhibin assays for monitoring ovarian cancer. Three new inhibin alpha-subunit (alphaC) ELISAs were developed using monoclonal antibodies directed to three nonoverlapping peptide regions of the alphaC region of the inhibin alpha-subunit. To characterize serum inhibin molecular wt forms present in women with ovarian cancer, existing inhibin immunoassays (inhibin A, inhibin B, and pro-alphaC) and the new alphaC ELISAs were applied to sera from women with granulosa cell tumors and mucinous carcinomas previously fractionated using a combined immunoaffinity chromatography, preparative SDS-PAGE, and electroelution procedure. The distribution and molecular size of dimeric inhibins and alpha-subunit detected were consistent with known mol wt forms of inhibins A and B and inhibin alpha-subunit and their precursor forms present in serum and follicular fluid from healthy women. The alphaC ELISAs recognized all known forms of inhibin and the free inhibin alpha-subunit, although differences between alphaC ELISAs were observed in their ability to detect high mol wt forms. To assess which of the alphaC ELISAs was preferred in application to ovarian cancer, the alphaC ELISAs were applied to serum from a range of normal postmenopausal women (n = 61) and postmenopausal women (n = 152) with ovarian (serous, mucinous, endometrioid, clear cell carcinomas, and granulosa cell tumors) and nonovarian (breast and colon) cancers. Despite differences in their ability to detect high mol wt forms of inhibin, the alphaC ELISAs showed similar sensitivity (i.e. proportion of cancer patients correctly detected) and specificity (proportion of controls correctly detected) indexes in the detection of mucinous carcinomas (84% and 95%) and granulosa cell tumors (100% and 95%) compared with earlier inhibin RIA or polyclonal antibody-based immunofluorometric assays. A combination of the alphaC ELISAs with the CA125 assay, an ovarian tumor marker that has a high sensitivity and specificity for other ovarian cancers (serous, clear cell, and endometrioid), resulted in an increase in sensitivity/specificity indexes (95% and 95%) for the all ovarian cancer group. These new monoclonal antibody-based inhibin alphaC ELISAs now provide practical and sensitive assays suitable for evaluation as diagnostic tests for monitoring ovarian cancers.

Paclitaxel and Carboplatin With or Without Bevacizumab in Treating Patients With Stage II, Stage III, or Stage IV Ovarian Epithelial Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer

ClinicalTrials.gov

2017-12-28

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

Paclitaxel, Bevacizumab And Adjuvant Intraperitoneal Carboplatin in Treating Patients Who Had Initial Debulking Surgery for Stage II, Stage III, or Stage IV Ovarian Epithelial, Primary Peritoneal, or Fallopian Tube Cancer

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; Stage II Ovarian Epithelial Cancer; Stage III Ovarian Epithelial Cancer; Stage IV Ovarian Epithelial Cancer

miRNA expression profiling in formalin-fixed paraffin-embedded endometriosis and ovarian cancer samples

PubMed Central

Braicu, Ovidiu-Leonard; Budisan, Liviuta; Buiga, Rares; Jurj, Ancuta; Achimas-Cadariu, Patriciu; Pop, Laura Ancuta; Braicu, Cornelia; Irimie, Alexandru; Berindan-Neagoe, Ioana

2017-01-01

Endometriosis is an inflammatory pathology associated with a negative effect on life quality. Recently, this pathology was connected to ovarian cancer, in particular with endometrioid ovarian cancer. microRNAs (miRNAs) are a class of RNA transcripts ~19–22 nucleotides in length, the altered miRNA pattern being connected to pathological status. miRNAs are highly stable transcripts, and these can be assessed from formalin-fixed paraffin-embedded (FFPE) samples leading to the identification of miRNAs that could be developed as diagnostic and prognostic biomarkers, in particular those involved in malignant transformation. The aim of our study was to evaluate miRNA expression pattern in FFPE samples from endometriosis and ovarian cancer patients using PCR-array technology and also to compare the differential expression pattern in ovarian cancer versus endometriosis. For the PCR-array study, we have used nine macrodissected FFPE samples from endometriosis tissue, eight samples of ovarian cancers and five normal ovarian tissues. Quantitative real-time PCR (qRT-PCR) was used for data validation in a new patient cohort of 17 normal samples, 33 endometriosis samples and 28 ovarian cancer macrodissected FFPE samples. Considering 1.5-fold expression difference as a cut-off level and a P-value <0.05, we have identified four miRNAs being overexpressed in endometrial tissue, while in ovarian cancer 15 were differentially expressed (nine overexpressed and six downregulated). The expression level was confirmed by qRT-PCR for miR-93, miR-141, miR-155, miR-429, miR-200c, miR-205 and miR-492. Using the interpretative program Ingenuity Pathway Analysis revealed several deregulated pathways due to abnormal miRNA expression in endometriosis and ovarian cancer, which in turn is responsible for pathogenesis; this differential expression of miRNAs can be exploited as a therapeutic target. A higher number of altered miRNAs were detected in endometriosis versus ovarian cancer tissue, most of them being linked with epithelial-to-mesenchymal transition. PMID:28894379

Molecular profiling and commercial predication assays in ovarian cancer: still not ready for prime time?

PubMed

Kohn, Elise C

2014-01-01

Short of early detection to allow curative primary intervention, the other major barrier to further success in treatment of ovarian cancers is matching the best treatment to the proper ovarian cancer type and to the individual patient. There are several decades of experience applying in vitro chemoresponse testing for solid tumors including ovarian cancer. This concept, first described in 1979, has yet to receive level one evidence supporting its application, despite the testing of numerous assays commercially as well as in academic centers and its use for tens of thousands of patients at a significant cost. The approach-rather than undergoing rigorous scientific examination-is now being muddied by the development of commercial molecular profiling assays from which treatment suggestions are provided. Molecular profiling as a research tool has added value to our understanding and treatment of patients with ovarian cancer. Morphologic and histochemical characterizations coupled now with increasing knowledge of ovarian cancer type-specific molecular patterns is improving our ability to properly diagnosis ovarian cancer type and thus guide therapy. With the exception of the role of germ-line and possibly somatic BRCA1 and BRCA2 mutations and their true predictiveness for probable response to poly(ADP-ribose) polymerase inhibition, molecular typing and profiling has yet to identify druggable molecular targets in ovarian cancer. Its use should be continued as a research and learning tool, and its results should be subjected to clinical trial validation. For very different reasons, neither chemoresponse assays nor molecular profiling are ready for prime time, yet.

Ovarian Cancer Knowledge in Women and Providers Following Education with Inside Knowledge Campaign Materials.

PubMed

Puckett, Mary C; Townsend, Julie S; Gelb, Cynthia A; Hager, Polly; Conlon, Amy; Stewart, Sherri L

2017-06-24

Because no effective methods for preventing or screening for ovarian cancer exist, symptom recognition is integral to its early detection. The Centers for Disease Control and Prevention's Inside Knowledge: Get the Facts about Gynecologic Cancer campaign was developed to raise awareness and educate women and providers about risk factors, symptoms, recommended screening, and prevention strategies for the five main gynecologic cancers, including ovarian cancer. Inside Knowledge campaign materials were utilized by CDC's National Comprehensive Cancer Control Program grantees to educate women and providers about gynecologic cancer from 2014 to 2015. Grantees recruited participants and held educational sessions using Inside Knowledge materials. Questionnaires were given before and after the sessions to assess changes in awareness, confidence, and behavioral intentions around gynecologic cancer information and analyzed in 2016. This analysis focused on an assessment of changes related to ovarian cancer information. Participants' knowledge increased after educational sessions. Among women, there were increases in correctly identifying that the Papanicolaou (Pap) test does not screen for ovarian cancer (89.2%) and that genetic testing is available (77.9%). There was a lower increase in knowledge that HPV is not a cause of ovarian cancer (56.4%). Providers and women reported significant increases in their confidence in their ability to talk to each other about gynecologic cancer post-session. Ovarian cancer awareness, confidence, and related behaviors increased in participants exposed to Inside Knowledge materials. Using these materials to increase knowledge could lead to more empowered patients, better provider-patient communications, and improved care for gynecologic cancers, including ovarian cancer.

Disorders of Sex Development with Testicular Differentiation in SRY-Negative 46,XX Individuals: Clinical and Genetic Aspects.

PubMed

Grinspon, Romina P; Rey, Rodolfo A

2016-01-01

Virilisation of the XX foetus is the result of androgen excess, resulting most frequently from congenital adrenal hyperplasia in individuals with typical ovarian differentiation. In rare cases, 46,XX gonads may differentiate into testes, a condition known as 46,XX testicular disorders of sex development (DSD), or give rise to the coexistence of ovarian and testicular tissue, a condition known as 46,XX ovotesticular DSD. Testicular tissue differentiation may be due to the translocation of SRY to the X chromosome or an autosome. In the absence of SRY, overexpression of other pro-testis genes, e.g. SOX family genes, or failure of pro-ovarian/anti-testis genes, such as WNT4 and RSPO1, may underlie the development of testicular tissue. Recent experimental and clinical evidence giving insight into SRY-negative 46,XX testicular or ovotesticular DSD is discussed. © 2016 S. Karger AG, Basel.

Collecting Tumor Samples From Patients With Gynecological Tumors

ClinicalTrials.gov

2016-10-26

Borderline Ovarian Clear Cell Tumor; Borderline Ovarian Serous Tumor; Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Childhood Embryonal Rhabdomyosarcoma; Childhood Malignant Ovarian Germ Cell Tumor; Endometrioid Stromal Sarcoma; Gestational Trophoblastic Tumor; Malignant Mesothelioma; Malignant Ovarian Epithelial Tumor; Melanoma; Neoplasm of Uncertain Malignant Potential; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Paget Disease of the Vulva; Recurrent Cervical Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Ovarian Germ Cell Tumor; Recurrent Primary Peritoneal Carcinoma; Recurrent Uterine Corpus Carcinoma; Recurrent Vaginal Carcinoma; Recurrent Vulvar Carcinoma; Stage I Ovarian Cancer; Stage I Uterine Corpus Cancer; Stage I Vaginal Cancer; Stage I Vulvar Cancer; Stage IA Cervical Cancer; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Cancer; Stage IA Ovarian Germ Cell Tumor; Stage IB Cervical Cancer; 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 II Uterine Corpus Cancer; Stage II Vaginal Cancer; Stage II Vulvar Cancer; Stage IIA Cervical Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIA Ovarian Germ Cell Tumor; Stage IIB Cervical Cancer; 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 III Borderline Ovarian Surface Epithelial-Stromal Tumor; Stage III Cervical Cancer; Stage III Uterine Corpus Cancer; Stage III Vaginal Cancer; Stage III Vulvar Cancer; 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 Borderline Ovarian Surface Epithelial-Stromal Tumor; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer; Stage IV Uterine Corpus Cancer; Stage IVA Cervical Cancer; Stage IVA Vaginal Cancer; Stage IVB Cervical Cancer; Stage IVB Vaginal Cancer; Stage IVB Vulvar Cancer; Uterine Corpus Cancer; Uterine Corpus Leiomyosarcoma; Vulvar Squamous Cell Carcinoma

Is endometrioma-associated damage to ovarian reserve progressive? Insights from IVF cycles.

PubMed

Benaglia, Laura; Castiglioni, Marta; Paffoni, Alessio; Sarais, Veronica; Vercellini, Paolo; Somigliana, Edgardo

2017-10-01

The relation between endometriomas and damage to ovarian reserve remains controversial. In this study, we hypothesized that this damage may not be present at the time of endometrioma formation but may conversely gradually develop over time. To investigate the possibility of a time-related detrimental effect of endometriomas on ovarian reserve, we retrospectively selected 29 women with unilateral cysts who underwent at least two IVF cycles at least 6 months apart and evaluated ovarian responsiveness over time. Women were excluded if they conceived, developed new endometriomas or necessitated new medical or surgical therapies for endometriosis during the interval between the two cycles, RESULTS: The mean±SD of the diameter of the endometriomas was 26±8mm. Most women (n=25) had only one endometrioma. In the first cycle, the number of developing follicles in the affected and contralateral intact gonads was 4.9±2.5 and 5.9±2.4, respectively (p=0.10). In the second cycle, it was 5.0±2.9 and 6.0±2.8, respectively (p=0.13). The median (Interquartile Range) proportion of follicles developing in the affected ovaries in the first and second cycles was 44% (31-58%) and 44% (35-55%), respectively (p=0.97). Subgroup analyses according to the duration of the time interval between the two assessments, the dimension of the endometriomas and the history of previous surgery for endometriosis did not show subgroups at significant risk of time-related damage. We failed to observe an endometrioma-related reduction of ovarian responsiveness with time. However, evidence from larger series obtained in women carrying larger cysts and enrolled for longer time period of time are required for a definitive conclusion. Copyright © 2017 Elsevier B.V. All rights reserved.

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

Gonadotropin and intra-ovarian signals regulating follicle development and atresia: the delicate balance between life and death.

PubMed

Craig, Jesse; Orisaka, Makoto; Wang, Hongmei; Orisaka, Sanae; Thompson, Winston; Zhu, Cheng; Kotsuji, Fumikazu; Tsang, Benjamin K

2007-05-01

Regulation of mammalian follicular development is tightly regulated by both cell death and survival signals, including endocrine (e.g. gonadotropin) and intra-ovarian regulators (e.g. Nodal and GDF9). The destiny of the individual follicle (growth/ovulation or atresia) is dependent on a delicate balance in the expression and action of factors promoting follicular cell proliferation, growth and differentiation, and of those promoting programmed cell death (apoptosis). Development of the follicle from the primordial to preantral stage is regulated by oocyte-derived factors including GDF9 and BMP15, and is not dependent on gonadotropin support (gonadotropin-independent stage). As the follicle transits into the early antral stage it becomes responsive to gonadotropin (gonadotropin-responsive stages) and further development renders the follicle completely dependent on the presence of gonadotropin while modulated by intra-ovarian regulators (gonadotropin-dependent). Follicle fate is also regulated by pro-apoptotic factors such as the intraovarian regulator Nodal, which is secreted by the theca and promotes apoptosis of differentiated granulosa cells through a mechanism involving Smad2 signaling and suppression of the PI3K/Akt pathway. The intracellular protein prohibitin (PHB) appears to have a dual role during folliculogenesis; acting as a cell survival factor in undifferentiated cells, and as a pro-apoptotic factor following differentiation. Further investigations of the interplay between these endocrine and ovarian regulators will lead to a better understanding into the regulation of follicular development and atresia, allowing development of new techniques for assisted reproduction.

Triennial Reproduction Symposium: The ovarian follicular reserve in cattle: What regulates its formation and size?1,2

PubMed Central

Fortune, J. E.; Yang, M. Y.; Allen, J. J.; Herrick, S. L.

2017-01-01

The ovarian follicular reserve has been linked to fertility in cattle. Young adult cattle with low vs. high numbers of antral follicles ≥ 3 mm in diameter in follicular waves also have fewer preantral follicles and decreased fertility. This underscores the importance of understanding the factors that regulate early follicular development and establish the ovarian follicular reserve, but little is known about how the follicular reserve is first established. In ruminants and humans, follicles form during fetal life, but there is a gap (about 50 d in cattle) between the appearance of the first primordial follicles and the first growing, primary follicles. In this review we present evidence that in cattle, fetal ovarian steroids (i.e., estradiol and progesterone) are negative regulators of both follicle formation and of the acquisition by newly formed follicles of the capacity to activate (i.e., initiate growth). The results indicate that capacity to activate is linked to the completion of meiotic prophase I by the oocyte. The inhibitory effects of estradiol on follicle activation were found to be reversible and correlated with inhibition of the progression of meiotic prophase I. Fetal bovine ovaries produce steroid hormones and production varies considerably during gestation and in a pattern consistent with the hypothesis that they inhibit follicle formation and capacity of newly formed follicles to activate in vivo. However, little was known about how steroid production is regulated. In our studies, both LH and FSH stimulated progesterone and estradiol production by ovarian pieces in vitro. The addition of testosterone to the culture medium enhanced estradiol production, especially when FSH was also present, but inhibited progesterone production, even in the presence of gonadotropins. Evidence is also presented for effects of maternal nutrition and health and for potential effects of estrogenic endocrine-disrupting chemicals on the size of the ovarian follicular reserve established during fetal life. In summary, fetal ovarian steroids may be important regulators of the early stages of follicular development in cattle. Therefore, external factors that alter steroid production or action may affect the size of the ovarian follicular reserve. PMID:23736047

Regulation of cell death and cell survival gene expression during ovarian follicular development and atresia.

PubMed

Jiang, Jin-Yi; Cheung, Carmen K M; Wang, Yifang; Tsang, Benjamin K

2003-01-01

Mammalian ovarian follicular development and atresia is closely regulated by the cross talk of cell death and cell survival signals, which include endocrine hormones (gonadotropins) and intra-ovarian regulators (gonadal steroids, cytokines and growth factors). The fate of the follicle is dependent on a delicate balance in the expression and actions of factors promoting follicular cell proliferation, growth and differentiation and of those inducing programmed cell death (apoptosis). As an important endocrine hormone, FSH binds to its granulosa cell receptors and promotes ovarian follicle survival and growth not only by stimulating proliferation and estradiol secretion of these cells, but also inhibiting the apoptosis by up-regulating the expression of intracellular anti-apoptotic proteins, such as XIAP and FLIP. In addition, intra-ovarian regulators, such as TGF-alpha and TNF-alpha, also play an important role in the control of follicular development and atresia. In response to FSH, Estradiol-17 beta synthesized from the granulosa cells stimulates thecal expression of TGF-alpha, which in turn increases granulosa cell XIAP expression and proliferation. The death receptor and ligand, Fas and Fas ligand, are expressed in granulosa cells following gonadotropin withdrawal, culminating in caspase-mediated apoptosis and follicular atresia. In contrast, TNF-alpha has both survival and pro-apoptotic function in the follicle, depending on the receptor subtype activated, but has been shown to promote granulosa cell survival by increasing XIAP and FLIP expression via the IkappaB-NFkappaB pathway. The pro-apoptotic action of TNF-alpha is mediated through the activation of caspases, via its receptor- (i.e. Caspases-8 and -3) and mitochrondria- (i.e. Caspase-9 and -3) death pathways. In the present manuscript, we have reviewed the actions and interactions of gonadotropins and intra-ovarian regulators in the control of granulosa cell fate and ultimately follicular destiny. We have highlighted the role and regulation of granulosa cell XIAP and FLIP expression, as well as their interactions with the death signaling pathways in the maintenance of granulosa cell survival during follicular development. We have provided strong evidence for these intracellular survival factors as key determinants for ovarian follicular destiny (growth versus atresia), the expression of which is regulated by a highly integrated endocrine, paracrine and autocrine mechanism. Further studies in these aspects will lead to a better understanding of the molecular and cellular regulation of follicular development and atresia, and provide invaluable insight into novel strategies in assisted reproduction in human infertility as well as in increasing reproductive efficiency in livestock industries.

Oral contraceptive pills induced hemichorea in an adolescent female with polycystic ovarian disease.

PubMed

Sharmila, Vijayan; Babu, Thirunavukkarasu Arun

2015-01-01

Chorea is a neurological adverse effect of oral contraceptive pills (OCPs). The onset of chorea following OCPs usage varies widely from few weeks to several years. We report a rare case of chorea which developed within a week of starting OCPs in an adolescent girl with polycystic ovarian disease.

The putative G-protein coupled estrogen receptor agonist G-1 suppresses proliferation of ovarian and breast cancer cells in a GPER-independent manner

PubMed Central

Wang, Cheng; Lv, Xiangmin; Jiang, Chao; Davis, John S

2012-01-01

G-protein coupled estrogen receptor 1 (GPER) plays an important role in mediating estrogen action in many different tissues under both physiological and pathological conditions. G-1 (1-[4-(6-bromobenzo[1,3]dioxol-5yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta [c]quinolin-8-yl]-ethanone) has been developed as a selective GPER agonist to distinguish estrogen actions mediated by GPER from those mediated by classic estrogen receptors. In the present study, we surprisingly found that G-1 suppressed proliferation and induced apoptosis of KGN cells (a human ovarian granulosa cell tumor cell line), actions that were not blocked by a selective GPER antagonist G15 or siRNA knockdown of GPER. G-1 also suppressed proliferation and induced cell apoptosis in GPER-negative HEK-293 cells and MDA-MB 231 breast cancer cells. Our results demonstrate that G-1 suppresses proliferation of ovarian and breast cancer cells in a GPER-independent manner. G-1 may be a candidate for the development of drugs against ovarian and breast cancer. PMID:23145207

Current treatment options and drug delivery systems as potential therapeutic agents for ovarian cancer: a review.

PubMed

Ye, Hongye; Karim, Anis Abdul; Loh, Xian Jun

2014-12-01

Ovarian cancer is one of the most common and deadliest gynecologic cancer with about 75% of the patients presenting in advanced stages. The introduction of intraperitoneal chemotherapy in 2006 had led to a 16 month improvement in the overall survival. However, catheter-related complication and the complexity of the procedure had deterred intraperitoneal route as the preferred route of treatment. Other alternative treatments had been developed by incorporating other FDA-approved agents or procedures such as pegylated liposomal doxorubicin (PLD), hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) and the administration of bevacizumab. Various clinical trials were conducted on these alternatives as both the first-line treatment and second- or third-line therapy for the recurrent disease. The outcome of these studies were summarized and discussed. A prospective improvement in the treatment of ovarian cancer could be done through the use of a drug delivery system. Selected promising recent developments in ovarian cancer drug delivery systems using different delivery vehicles, surface modifications, materials and drugs were also reviewed. Copyright © 2014 Elsevier B.V. All rights reserved.

Proteomic Data Resources for EDRN Ovary Cancer Researchers within the EDRN — EDRN Public Portal

Cancer.gov

This project will generate a highly valuable data resource and make it available to all EDRN ovarian cancer researchers. The resource will include comprehensive proteomic (tandem mass spectrometry, MS/MS) data generated from plasma samples that have been collected between four months and four years prior to clinical detection of ovarian cancer. These pre-clinical samples, provided from the Beta Carotene and Retinol Efficacy Trial (CARET) prospective study, will be interrogated using IPAS, the proteomic profiling method developed by the Hanash Laboratory and with the quantitative methods developed by the McIntosh laboratory. In addition, we will combine these pre-clinical data with already completed IPAS interrogations of plasma collected at the time of ovarian cancer diagnosis. Thus together we will provide information on both pre-clinical and clinical behavior of a large number of proteins. Based on our preliminary work we are able to quantify over 500 plasma proteins in each of these experiments, many of which are putative ovarian cancer biomarkers, showing the platform is capable of providing useful information regarding biomarker candidates.

Development of Nanoscale Approaches for Ovarian Cancer Therapeutics and Diagnostics

PubMed Central

Engelberth, Sarah A.; Hempel, Nadine; Bergkvist, Magnus

2014-01-01

Ovarian cancer is the deadliest of all gynecological cancers and the fifth leading cause of death due to cancer in women. This is largely due to late-stage diagnosis, poor prognosis related to advanced-stage disease, and the high recurrence rate associated with development of chemoresistance. Survival statistics have not improved significantly over the last three decades, highlighting the fact that improved therapeutic strategies and early detection require substantial improvements. Here, we review and highlight nanotechnology-based approaches that seek to address this need. The success of Doxil, a PEGylated liposomal nanoencapsulation of doxorubicin, which was approved by the FDA for use on recurrent ovarian cancer, has paved the way for the current wave of nanoparticle formulations in drug discovery and clinical trials. We discuss and summarize new nanoformulations that are currently moving into clinical trials and highlight novel nanotherapeutic strategies that have shown promising results in preclinical in vivo studies. Further, the potential for nanomaterials in diagnostic imaging techniques and the ability to leverage nanotechnology for early detection of ovarian cancer are also discussed. PMID:25271436

Carboplatin and Paclitaxel or Oxaliplatin and Capecitabine With or Without Bevacizumab as First-Line Therapy in Treating Patients With Newly Diagnosed Stage II-IV or Recurrent Stage I Epithelial Ovarian or Fallopian Tube Cancer

ClinicalTrials.gov

2017-08-21

Borderline Ovarian Mucinous Tumor; Ovarian Mucinous Cystadenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Cancer; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Cancer; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer

YKL-40 in Serum Samples From Patients With Newly Diagnosed Stage III-IV Ovarian Epithelial, Primary Peritoneal Cavity, or Fallopian Tube Cancer Receiving Chemotherapy

ClinicalTrials.gov

2018-05-21

Fallopian Tube Adenocarcinoma; Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Malignant Ovarian Brenner Tumor; Malignant Ovarian Clear Cell Tumor; Malignant Ovarian Endometrioid Tumor; Malignant Ovarian Mixed Epithelial Tumor; Malignant Ovarian Mucinous Tumor; Malignant Ovarian Neoplasm; Malignant Ovarian Serous Tumor; Malignant Ovarian Transitional Cell Tumor; Ovarian Adenocarcinoma; Primary Peritoneal Serous Adenocarcinoma; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

Everolimus and Letrozole in Treating Patients With Recurrent Hormone Receptor Positive Ovarian, Fallopian Tube, or Primary Peritoneal Cavity Cancer

ClinicalTrials.gov

2018-03-05

Ovarian Endometrioid Adenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Serous Surface Papillary Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Ovarian Germ Cell Tumor; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Ovarian Carcinoma

Prostaglandins and reproduction in female farm animals.

PubMed

Weems, C W; Weems, Y S; Randel, R D

2006-03-01

Prostaglandins impact on ovarian, uterine, placental, and pituitary function to regulate reproduction in female livestock. They play important roles in ovulation, luteal function, maternal recognition of pregnancy, implantation, maintenance of gestation, microbial-induced abortion, parturition, postpartum uterine and ovarian infections, and resumption of postpartum ovarian cyclicity. Prostaglandins have both positive and negative effects on reproduction; they are used to synchronize oestrus, terminate pseudopregnancy in mares, induce parturition, and treat retained placenta, luteinized cysts, pyometra, and chronic endometritis. Improved therapeutic uses for prostaglandins will be developed when we understand better their involvement in implantation, maintenance of luteal function, and establishment and maintenance of pregnancy.

Ovarian tissue characterization using bulk optical properties

NASA Astrophysics Data System (ADS)

Tavakoli, B.; Xu, Y.; Zhu, Q.

2013-03-01

Ovarian cancer, the deadliest of all gynecologic cancers, is not often found in its early stages due to few symptoms and no reliable screening test. Optical imaging has a great potential to improve the ovarian cancer detection and diagnosis. In this study we have characterized the bulk optical properties of 26 ex-vivo human ovaries using a Diffuse Optical Tomography system. The quantitative values indicated that, in the postmenopausal group, malignant ovaries showed significantly lower scattering coefficient than normal ones. The scattering parameter is largely related to the collagen content that has shown a strong correlation with the cancer development.

Tracking the origin of simultaneous endometrial and ovarian cancer by next-generation sequencing - a case report.

PubMed

Valtcheva, Nadejda; Lang, Franziska M; Noske, Aurelia; Samartzis, Eleftherios P; Schmidt, Anna-Maria; Bellini, Elisa; Fink, Daniel; Moch, Holger; Rechsteiner, Markus; Dedes, Konstantin J; Wild, Peter J

2017-01-19

Endometrioid adenocarcinoma of the uterus and ovarian endometrioid carcinoma share many morphological and molecular features. Differentiation between simultaneous primary carcinomas and ovarian metastases of an endometrial cancer may be very challenging but is essential for prognostic and therapeutic considerations. In the present case study of a 33 year-old patient we used targeted amplicon next-generation re-sequencing for clarifying the origin of synchronous endometrioid cancer of the corpus uteri and the left ovary. The patient developed a metachronous lung metastasis of an endometrioid adenocarcinoma four years after hyster- and adnexectomy, vaginal brachytherapy and treatment with the synthetic steroid tibolone. Removal of the metastasis and megestrol treatment for seven years led to a complete remission. A total of 409 genes from the Ampliseq Comprehensive Cancer Panel (Ion Torrent, Thermo Fisher) were analysed by next generation sequencing and mutations in 10 genes, including ARID1A, CTNNB1, PIK3CA and PTEN were identified and confirmed by Sanger sequencing. Primary endometrial as well as ovarian cancer showed an identical mutational profile, suggesting the presence of an ovarian metastasis of the endometrial cancer, rather than a simultaneous endometrial and ovarian cancer. The metachronous lung metastasis showed a different mutational profile compared to the primary cancer. Immunohistochemical staining of the corresponding proteins suggested that the tumour development was driven by alterations in the protein function rather than by changes of the protein abundance in the cell. Our results have demonstrated next generation sequencing as a valuable tool in the differentiation of synchronous primary tumours and metastases, which has an important impact on the clinical decision making process. Similar to breast cancer, targeted therapies based on mutational tumour profiling will become increasingly important in endometrial and ovarian cancer. In summary, our results support the usage of next generation sequencing as a supplementary diagnostic tool, assisting in personalized precision medicine.

Transvaginal Aspiration of Ovarian Cysts: Long-Term Follow-up

DOE Office of Scientific and Technical Information (OSTI.GOV)

Duke, D.; Colville, J.; Keeling, A.

2006-06-15

Background and purpose. Transvaginal aspiration of ovarian cysts has been advocated as a viable alternative to surgery in patients who are high-risk surgical candidates. We describe a retrospective study evaluating the results of transvaginal aspirations of benign ovarian cysts in patients at increased surgical risk, focusing on long-term follow-up for recurrence of the cyst and/or development of malignancy. Methods. Twenty-four women with ovarian cysts underwent 34 transvaginal drainages between October 1998 and December 2004. All patients were referred following diagnosis of a persistent ovarian cyst with a benign appearance on ultrasound. All patients were unsuitable candidates for surgery (history ofmore » previous pelvic surgery, n = 21; high risk for anesthesia, n = 1; and unsuitable for laparoscopy due to obesity, n = 2). Patients with a history of pregnancy, acute abdominal symptoms, or previous gynecologic malignancy were excluded. A 20G x 20 cm Chiba needle was used for transvaginal aspiration using an endocavity probe (Acuson XP, Mountain View, CA, USA; Siemens Sololine, Erlangen, Germany) and intravenous sedoanalgesia. Cysts were aspirated to dryness. Results. Long-term follow-up of patients was performed and revealed a recurrence rate of 75%. Eighty-three percent of cysts on the left and 42% of those on the right recurred. Nine of 15 (60%) patients with recurrence required further intervention. Two of 9 underwent surgical intervention only, 4 of 9 had repeat transvaginal aspiration(s) performed, and 3 of 9 had a combination of both transvaginal aspiration and surgery. No patient developed ovarian malignancy. Conclusion. Transvaginal cyst aspiration has many advantages including short hospital stay, rapid recovery, excellent patient tolerance, and a low rate of procedure-related complications. Our study demonstrates that ovarian cyst recurrence following transvaginal drainage is a more significant problem than previously documented, especially if the cyst is on the left side. However, when recurrences do occur, repeat transvaginal aspirations may be considered in the symptomatic patient.« less

Prevalence of c-KIT Mutations in Gonadoblastoma and Dysgerminomas of Patients with Disorders of Sex Development (DSD) and Ovarian Dysgerminomas

PubMed Central

Hersmus, Remko; Stoop, Hans; van de Geijn, Gert Jan; Eini, Ronak; Biermann, Katharina; Oosterhuis, J. Wolter; DHooge, Catharina; Schneider, Dominik T.; Meijssen, Isabelle C.; Dinjens, Winand N. M.; Dubbink, Hendrikus Jan; Drop, Stenvert L. S.; Looijenga, Leendert H. J.

2012-01-01

Activating c-KIT mutations (exons 11 and 17) are found in 10–40% of testicular seminomas, the majority being missense point mutations (codon 816). Malignant ovarian dysgerminomas represent ∼3% of all ovarian cancers in Western countries, resembling testicular seminomas, regarding chromosomal aberrations and c-KIT mutations. DSD patients with specific Y-sequences have an increased risk for Type II Germ Cell Tumor/Cancer, with gonadoblastoma as precursor progressing to dysgerminoma. Here we present analysis of c-KIT exon 8, 9, 11, 13 and 17, and PDGFRA exon 12, 14 and 18 by conventional sequencing together with mutational analysis of c-KIT codon 816 by a sensitive and specific LightCycler melting curve analysis, confirmed by sequencing. The results are combined with data on TSPY and OCT3/4 expression in a series of 16 DSD patients presenting with gonadoblastoma and dysgerminoma and 15 patients presenting pure ovarian dysgerminomas without DSD. c-KIT codon 816 mutations were detected in five out of the total of 31 cases (all found in pure ovarian dysgerminomas). A synonymous SNP (rs 5578615) was detected in two patients, one DSD patient (with bilateral disease) and one patient with dysgerminoma. Next to these, three codon N822K mutations were detected in the group of 15 pure ovarian dysgerminomas. In total activating c-KIT mutations were found in 53% of ovarian dysgerminomas without DSD. In the group of 16 DSD cases a N505I and D820E mutation was found in a single tumor of a patient with gonadoblastoma and dysgerminoma. No PDGFRA mutations were found. Positive OCT3/4 staining was present in all gonadoblastomas and dysgerminomas investigated, TSPY expression was only seen in the gonadoblastoma/dysgerminoma lesions of the 16 DSD patients. This data supports the existence of two distinct but parallel pathways in the development of dysgerminoma, in which mutational status of c-KIT might parallel the presence of TSPY. PMID:22937135

Ovarian function and reproductive outcomes of female patients with systemic lupus erythematosus and the strategies to preserve their fertility.

PubMed

Oktem, Ozgur; Guzel, Yılmaz; Aksoy, Senai; Aydin, Elvin; Urman, Bulent

2015-03-01

Systemic lupus erythematosus (SLE) is a chronic autoimmune systemic disease that mainly affects women of reproductive age. Emerging data from recent molecular studies show us that estrogen hormone plays a central role in the development of this disease. By acting via its cognate receptors ERα and ERβ expressed on immune cells, estrogen can modulate immune function in both the innate and adaptive immune responses. Interestingly, estrogen may also evoke autoimmune responses after binding to B lymphocytes leading to the generation of high-affinity autoantibodies and proinflammatory cytokines (so-called estrogen-induced autoimmunity). Unfortunately, reproductive function of young female patients with this disease is commonly compromised by different pathophysiologic processes. First, ovarian reserve is diminished even in the presence of mild disease suggesting a direct impact of the disease itself on ovarian function possibly due to ovarian involvement in the form of autoimmune oophoritis. Second, SLE patients with severe manifestations of the disease are treated with alkylating chemotherapy agent cyclophosphamide. Cyclophosphamide and other drugs of alkylating category have the highest gonadotoxicity. Therefore, SLE patients exposed to cyclophosphamide have a much higher risk of developing infertility and premature ovarian failure than do the counterparts who are treated with other less toxic treatments. Third, the functions of the hypothalamic pituitary ovarian axis are perturbed by chronic inflammatory state. And finally adverse pregnancy outcomes are more commonly observed in SLE patients such as fetal loss, preterm birth, intrauterine fetal growth restriction, preeclampsia-eclampsia, and fetal congenital heart block. We aimed in this review article to provide the readers an update on how estrogen hormone closely interacts with and induces lupus-prone changes in the immune system. We also discuss ovarian function and other reproductive outcomes in SLE patients and the current strategies to preserve their fertility in the light of the most recent evidence-based findings of the clinical trials and molecular studies.

Bevacizumab in Treating Patients With Recurrent Sex Cord-Stromal Tumors of the Ovary

ClinicalTrials.gov

2018-03-20

Malignant Ovarian Epithelial Tumor; Ovarian Granulosa Cell Tumor; Ovarian Gynandroblastoma; Ovarian Sertoli-Leydig Cell Tumor; Ovarian Sex Cord Tumor With Annular Tubules; Ovarian Sex Cord-Stromal Tumor; Ovarian Sex Cord-Stromal Tumor of Mixed or Unclassified Cell Types; Ovarian Steroid Cell Tumor

Paclitaxel, Polyglutamate Paclitaxel, or Observation in Treating Patients With Stage III or Stage IV Ovarian Epithelial, Peritoneal Cancer, or Fallopian Tube Cancer

ClinicalTrials.gov

2017-05-03

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 Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Primary Peritoneal Serous Adenocarcinoma; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

Safe and targeted anticancer therapy for ovarian cancer using a novel class of curcumin analogs

PubMed Central

2013-01-01

A diagnosis of advanced ovarian cancer is the beginning of a long and arduous journey for a patient. Worldwide, approximately half of the individuals undergoing therapy for advanced cancer will succumb to the disease, or consequences of treatment. Well-known and widely-used chemotherapeutic agents such as cisplatin, paclitaxel, 5-fluorouracil, and doxorubicin are toxic to both cancer and non-cancerous cells, and have debilitating side effects Therefore, development of new targeted anticancer therapies that can selectively kill cancer cells while sparing the surrounding healthy tissues is essential to develop more effective therapies. We have developed a new class of synthetic curcumin analogs, diarylidenyl-piperidones (DAPs), which have higher anticancer activity and enhanced bio-absorption than curcumin. The DAP backbone structure exhibits cytotoxic (anticancer) activity, whereas the N-hydroxypyrroline (-NOH) moiety found on some variants functions as a cellular- or tissue-specific modulator (antioxidant) of cytotoxicity. The anticancer activity of the DAPs has been evaluated using a number of ovarian cancer cell lines, and the safety has been evaluated in a number of non-cancerous cell lines. Both variations of the DAP compounds showed similar levels of cell death in ovarian cancer cells, however the compounds with the -NOH modification were less toxic to non-cancerous cells. The selective cytotoxicity of the DAP–NOH compounds suggests that they will be useful as safe and effective anticancer agents. This article reviews some of the key findings of our work with the DAP compounds, and compares this to some of the targeted therapies currently used in ovarian cancer therapy. PMID:23663277

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

Survival of gynecological cancers in Turkey: where are we at?

PubMed Central

Dundar, Selin; Kucukyildiz, Irem; Karaca, Mujdegul Zayifoglu; Boztas, Guledal; Turan, Semra Hatice; Hacikamiloglu, Ezgi; Keskinkilic, Bekir

2017-01-01

Objective To investigate the 5-year relative survival rates in gynecological cancers diagnosed and treated in Turkey by year 2009 and to compare the results with developed countries. Methods Data of patients diagnosed for ovarian, corpus uteri or cervix uteri cancer at year 2009 are collected from 9 national cancer registry centers. Date of deaths are retracted from governmental Identity Information Sharing System (KPS). In order to calculate relative survival rates, national general population mortality tables are obtained from Turkish Statistical Institute (TurkStat). Hakulinen method is used for computing curves by R program. Data for European, Asian and some developed countries were obtained from official web pages. Results A total of 1,553 patients are evaluated. Among these, 713 (45.9%) are corpus uteri cancers, while remaining 489 (31.5%) are ovarian and 351 (22.6%) are cervix uteri. Five-year overall relative survival rates are 85%, 50%, and 62% for corpus uteri, ovarian, and cervix uteri, respectively. These figures are between 73%–87% for corpus uteri, 31%–62% for ovarian and 61%–80% for cervix uteri in developed countries. Stage is the most important factor for survival in all cancers. Five-year relative survival rates in corpus uteri cancers are 92%, 66%, and 38% for localized, regional, and distant metastatic disease, respectively. These figures are 77%, 57%, and 29% for ovarian; 80%, 50%, and 22% for cervix uteri. Conclusion This is the first report from Turkey giving national overall relative survival for gynecological cancers from a population based cancer registry system. PMID:29027403

Survival of gynecological cancers in Turkey: where are we at?

PubMed

Gultekin, Murat; Dundar, Selin; Kucukyildiz, Irem; Karaca, Mujdegul Zayifoglu; Boztas, Guledal; Turan, Semra Hatice; Hacikamiloglu, Ezgi; Keskinkilic, Bekir

2017-11-01

To investigate the 5-year relative survival rates in gynecological cancers diagnosed and treated in Turkey by year 2009 and to compare the results with developed countries. Data of patients diagnosed for ovarian, corpus uteri or cervix uteri cancer at year 2009 are collected from 9 national cancer registry centers. Date of deaths are retracted from governmental Identity Information Sharing System (KPS). In order to calculate relative survival rates, national general population mortality tables are obtained from Turkish Statistical Institute (TurkStat). Hakulinen method is used for computing curves by R program. Data for European, Asian and some developed countries were obtained from official web pages. A total of 1,553 patients are evaluated. Among these, 713 (45.9%) are corpus uteri cancers, while remaining 489 (31.5%) are ovarian and 351 (22.6%) are cervix uteri. Five-year overall relative survival rates are 85%, 50%, and 62% for corpus uteri, ovarian, and cervix uteri, respectively. These figures are between 73%-87% for corpus uteri, 31%-62% for ovarian and 61%-80% for cervix uteri in developed countries. Stage is the most important factor for survival in all cancers. Five-year relative survival rates in corpus uteri cancers are 92%, 66%, and 38% for localized, regional, and distant metastatic disease, respectively. These figures are 77%, 57%, and 29% for ovarian; 80%, 50%, and 22% for cervix uteri. This is the first report from Turkey giving national overall relative survival for gynecological cancers from a population based cancer registry system. Copyright © 2017. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology

Epigenetic inactivation of TCF2 in ovarian cancer and various cancer cell lines

PubMed Central

Terasawa, K; Toyota, M; Sagae, S; Ogi, K; Suzuki, H; Sonoda, T; Akino, K; Maruyama, R; Nishikawa, N; Imai, K; Shinomura, Y; Saito, T; Tokino, T

2006-01-01

Transcription factor 2 gene (TCF2) encodes hepatocyte nuclear factor 1β (HNF1β), a transcription factor associated with development and metabolism. Mutation of TCF2 has been observed in renal cell cancer, and by screening aberrantly methylated genes, we have now identified TCF2 as a target for epigenetic inactivation in ovarian cancer. TCF2 was methylated in 53% of ovarian cancer cell lines and 26% of primary ovarian cancers, resulting in loss of the gene's expression. TCF2 expression was restored by treating cells with a methyltransferase inhibitor, 5-aza-2′deoxycitidine (5-aza-dC). In addition, chromatin immunoprecipitation showed deacetylation of histone H3 in methylated cells and, when combined with 5-aza-dC, the histone deacetylase inhibitor trichostatin A synergistically induced TCF2 expression. Epigenetic inactivation of TCF2 was also seen in colorectal, gastric and pancreatic cell lines, suggesting general involvement of epigenetic inactivation of TCF2 in tumorigenesis. Restoration of TCF2 expression induced expression of HNF4α, a transcriptional target of HNF1β, indicating that epigenetic silencing of TCF2 leads to alteration of the hepatocyte nuclear factor network in tumours. These results suggest that TCF2 is involved in the development of ovarian cancers and may represent a useful target for their detection and treatment. PMID:16479257

Peptidoglycan inhibits progesterone and androstenedione production in bovine ovarian theca cells.

PubMed

Magata, F; Horiuchi, M; Miyamoto, A; Shimizu, T

2014-08-01

Uterine bacterial infection perturbs uterine and ovarian functions in postpartum dairy cows. Peptidoglycan (PGN) produced by gram-positive bacteria has been shown to disrupt the ovarian function in ewes. The aim of this study was to determine the effect of PGN on steroid production in bovine theca cells at different stages of follicular development. Bovine theca cells isolated from pre- and post-selection ovarian follicles (<8.5mm and >8.5mm in diameter, respectively) were cultured in vitro and challenged with PGN. Steroid production was evaluated by measuring progesterone (P4) and androstenedione (A4) concentration in culture media after 48 h or 96 h of culture. Bovine theca cells expressed PGN receptors including Toll-like receptor 2 and nucleotide-binding oligomerization domain 1 and 2. Treatment with PGN (1, 10, or 50 μg/ml) led to a decrease in P4 and A4 production by theca cells in both pre- and post-selection follicles. The mRNA expression of steroidogenic enzymes were decreased by PGN treatment. Moreover, A4 production was further suppressed when theca cells of post-selection follicles were simultaneously treated by PGN and lipopolysaccharide (0.1, 1, or 10 μg/ml). These findings indicate that bacterial toxins may act locally on ovarian steroidogenic cells and compromise follicular development in postpartum dairy cows. Copyright © 2014 Elsevier Ltd. All rights reserved.

Isolation of Small SSEA-4-Positive Putative Stem Cells from the Ovarian Surface Epithelium of Adult Human Ovaries by Two Different Methods

PubMed Central

Virant-Klun, Irma; Skutella, Thomas; Hren, Matjaz; Gruden, Kristina; Cvjeticanin, Branko; Vogler, Andrej; Sinkovec, Jasna

2013-01-01

The adult ovarian surface epithelium has already been proposed as a source of stem cells and germinal cells in the literature, therefore it has been termed the “germinal epithelium”. At present more studies have confirmed the presence of stem cells expressing markers of pluripotency in adult mammalian ovaries, including humans. The aim of this study was to isolate a population of stem cells, based on the expression of pluripotency-related stage-specific embryonic antigen-4 (SSEA-4) from adult human ovarian surface epithelium by two different methods: magnetic-activated cell sorting and fluorescence-activated cell sorting. Both methods made it possible to isolate a similar, relatively homogenous population of small, SSEA-4-positive cells with diameters of up to 4 μm from the suspension of cells retrieved by brushing of the ovarian cortex biopsies in reproductive-age and postmenopausal women and in women with premature ovarian failure. The immunocytochemistry and genetic analyses revealed that these small cells—putative stem cells—expressed some primordial germ cell and pluripotency-related markers and might be related to the in vitro development of oocyte-like cells expressing some oocyte-specific transcription factors in the presence of donated follicular fluid with substances important for oocyte growth and development. The stemness of these cells needs to be further researched. PMID:23509763

Elesclomol Sodium and Paclitaxel in Treating Patients With Recurrent or Persistent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer

ClinicalTrials.gov

2017-05-02

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

Kisspeptin regulates ovarian steroidogenesis during delayed embryonic development in the fruit bat, Cynopterus sphinx.

PubMed

Anuradha; Krishna, Amitabh

2017-11-01

Cynopterus sphinx, a fruit bat, undergoes delayed embryonic development during the winter months, a period that corresponds to low levels of progesterone and estradiol synthesis by the ovary. Kisspeptins (KPs) are a group of neuropeptide hormones that act via G-protein coupled receptor 54 (GPR54) to stimulate hypothalamic secretion of Gonadotropin-releasing hormone, thereby regulating ovarian steroidogenesis, folliculogenesis, and ovulation. GPR54 is also expressed in the ovary, suggesting a direct role for KPs in ovarian steroidogenesis. The aim of present study was to determine if a low serum level of KP is responsible for reduced progesterone and estradiol levels during the period of delayed embryonic development in C. sphinx. Indeed, low serum KP abundance corresponded to reduced expression of GPR54 in ovarian luteal cells during the period of delayed development compared to normal development. In vitro and in vivo treatment with KP increased GPR54 abundance, via Extracellular signal regulated kinase and its downstream mediators, leading to increased progesterone synthesis in the ovary during delayed embryonic development. KP treatment also increased cholesterol uptake and elevated expression of Luteinizing hormone receptor and Steroid acute regulatory protein in the ovary, suggesting that elevation in circulating KP during delayed embryonic development may reactivate luteal activity. KPs may also enhance cell survival (BCL-2, reduced Caspase 3 activity) and angiogenesis (Vascular endothelium growth factor) during this period. The findings of this study thus demonstrate a regulatory role for KPs in the maintenance of luteal steroidogenesis during pregnancy in C. sphinx. © 2017 Wiley Periodicals, Inc.

Carboplatin and Paclitaxel With or Without Bevacizumab in Treating Patients With Stage III or Stage IV Ovarian Epithelial, Primary Peritoneal, or Fallopian Tube Cancer

ClinicalTrials.gov

2017-10-23

Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Malignant Ovarian Mixed Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Primary Peritoneal Serous Adenocarcinoma; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

Active Surveillance, Bleomycin, Carboplatin, Etoposide, or Cisplatin in Treating Pediatric and Adult Patients With Germ Cell Tumors

ClinicalTrials.gov

2017-06-02

Adult Germ Cell Tumor; Childhood Extracranial Germ Cell Tumor; Childhood Germ Cell Tumor; Extragonadal Embryonal Carcinoma; Grade 2 Immature Ovarian Teratoma; Grade 3 Immature Ovarian Teratoma; Malignant Germ Cell Tumor; Stage I Ovarian Choriocarcinoma; Stage I Ovarian Embryonal Carcinoma; Stage I Ovarian Teratoma; Stage I Ovarian Yolk Sac Tumor; Stage I Testicular Choriocarcinoma; Stage I Testicular Embryonal Carcinoma; Stage I Testicular Yolk Sac Tumor; Stage II Ovarian Choriocarcinoma; Stage II Ovarian Embryonal Carcinoma; Stage II Ovarian Yolk Sac Tumor; Stage II Testicular Choriocarcinoma; Stage II Testicular Embryonal Carcinoma; Stage II Testicular Yolk Sac Tumor; Stage III Ovarian Choriocarcinoma; Stage III Ovarian Embryonal Carcinoma; Stage III Ovarian Yolk Sac Tumor; Stage III Testicular Choriocarcinoma; Stage III Testicular Embryonal Carcinoma; Stage III Testicular Yolk Sac Tumor; Stage IV Ovarian Choriocarcinoma; Stage IV Ovarian Embryonal Carcinoma; Stage IV Ovarian Yolk Sac Tumor; Testicular Mixed Choriocarcinoma and Embryonal Carcinoma; Testicular Mixed Choriocarcinoma and Teratoma; Testicular Mixed Choriocarcinoma and Yolk Sac Tumor

Belinostat in Treating Patients With Advanced Ovarian Epithelial Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer or Ovarian Low Malignant Potential Tumors

ClinicalTrials.gov

2016-10-20

Fallopian Tube Carcinoma; Primary Peritoneal Carcinoma; Recurrent Borderline Ovarian Surface Epithelial-Stromal Tumor; Recurrent Ovarian Carcinoma; Stage III Borderline Ovarian Surface Epithelial-Stromal Tumor; Stage III Ovarian Cancer; Stage IV Borderline Ovarian Surface Epithelial-Stromal Tumor; Stage IV Ovarian Cancer

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

2017-10-18

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

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

Paclitaxel and Carboplatin or Bleomycin Sulfate, Etoposide Phosphate, and Cisplatin in Treating Patients With Advanced or Recurrent Sex Cord-Ovarian Stromal Tumors

ClinicalTrials.gov

2018-02-14

Ovarian Granulosa Cell Tumor; Ovarian Gynandroblastoma; Ovarian Sertoli-Leydig Cell Tumor; Ovarian Sex Cord Tumor With Annular Tubules; Ovarian Sex Cord-Stromal Tumor; Ovarian Sex Cord-Stromal Tumor of Mixed or Unclassified Cell Types; Ovarian Steroid Cell Tumor

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

ClinicalTrials.gov

2018-04-27

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

Molecular and cellular effects of chemicals disrupting steroidogenesis during early ovarian development of brown trout (Salmo trutta fario).

PubMed

a Marca Pereira, M L; Eppler, E; Thorpe, K L; Wheeler, J R; Burkhardt-Holm, P

2014-02-01

A range of chemicals found in the aquatic environment have the potential to influence endocrine function and affect sexual development by mimicking or antagonizing the effects of hormones, or by altering the synthesis and metabolism of hormones. The aim of this study was to evaluate whether the effects of chemicals interfering with sex hormone synthesis may affect the regulation of early ovarian development via the modulation of sex steroid and insulin-like growth factor (IGF) systems. To this end, ex vivo ovary cultures of juvenile brown trout (Salmo trutta fario) were exposed for 2 days to either 1,4,6-androstatriene-3,17-dione (ATD, a specific aromatase inhibitor), prochloraz (an imidazole fungicide), or tributyltin (TBT, a persistent organic pollutant). Further, juvenile female brown trout were exposed in vivo for 2 days to prochloraz or TBT. The ex vivo and in vivo ovarian gene expression of the aromatase (CYP19), responsible for estrogen production, and of IGF1 and 2 were compared. Moreover, 17β-estradiol (E2) and testosterone (T) production from ex vivo ovary cultures was assessed. Ex vivo exposure to ATD inhibited ovarian E2 synthesis, while T levels accumulated. However, ATD did not affect ex vivo expression of cyp19, igf1, or igf2. Ex vivo exposure to prochloraz inhibited ovarian E2 production, but did not affect T levels. Further prochloraz up-regulated igf1 expression in both ex vivo and in vivo exposures. TBT exposure did not modify ex vivo synthesis of either E2 or T. However, in vivo exposure to TBT down-regulated igf2 expression. The results indicate that ovarian inhibition of E2 production in juvenile brown trout might not directly affect cyp19 and igf gene expression. Thus, we suggest that the test chemicals may interfere with both sex steroid and IGF systems in an independent manner, and based on published literature, potentially lead to endocrine dysfunction and altered sexual development. Copyright © 2011 Wiley Periodicals, Inc., A Wiley Company.

Therapeutic Effect of Angiostatin Gene Transfer in a Murine Model of Endometriosis

PubMed Central

Dabrosin, Charlotta; Gyorffy, Steve; Margetts, Peter; Ross, Catherine; Gauldie, Jack

2002-01-01

Endometriosis, the growth of ectopic endometrial tissue, is a chronic recurrent disease affecting 10% of the female population causing dyspareunia, pelvic pain, dysmenorrhea, and infertility. Suppression of ovarian activity is the cornerstone of medical therapy with limited benefit and severe adverse effects. Angiogenesis plays a major role in the development of endometriosis suggesting that anti-angiogenic therapy would offer a new therapeutic approach. We report successful treatment of endometriosis in estrogen-supplemented ovariectomized mice by transient overexpression (6 to 10 days of duration) of the gene for a natural angiogenesis inhibitor angiostatin, delivered to the peritoneum by a replication-deficient adenovirus vector (AdAngiostatin). Established endometriosis was eradicated in 14 of 14 AdAngiostatin-treated animals, whereas 11 of 13 control animals showed full disease development. Administered to normal cycling mice for the same transient period, AdAngiostatin caused impaired ovarian function with suppressed corpus luteum development, decreased production of estradiol and progesterone, decreased ovarian and uterine weight, and increased body weight. AdAngiostatin treatment lowered the levels of sex steroids but did not induce total castration. Gene therapy with angiogenic inhibitors is a highly effective treatment for endometriosis, even in a host with preserved estrogen levels. However, local or targeted delivery of the gene must be considered to avoid prolonged systemic effects and impaired ovarian function. PMID:12213719

Multifunctional nanomedicine platform for concurrent delivery of chemotherapeutic drugs and mild hyperthermia to ovarian cancer cells.

PubMed

Taratula, Olena; Dani, Raj Kumar; Schumann, Canan; Xu, Hong; Wang, Andrew; Song, Han; Dhagat, Pallavi; Taratula, Oleh

2013-12-15

A multifunctional tumor-targeting delivery system was developed and evaluated for an efficient treatment of drug-resistant ovarian cancer by combinatorial therapeutic modality based on chemotherapy and mild hyperthermia. The engineered iron oxide nanoparticle (IONPs)-based nanocarrier served as an efficient delivery vehicle for doxorubicin and provided the ability to heat cancer cells remotely upon exposure to an alternating magnetic field (AMF). The nanocarrier was additionally modified with polyethylene glycol and LHRH peptide to improve its biocompatibility and ability to target tumor cells. The synthesized delivery system has an average size of 97.1 nm and a zeta potential close to zero, both parameters favorable for increased stability in biological media and decreased elimination by the immune system. The nanocarrier demonstrated faster drug release in acidic conditions that mimic the tumor environment. It was also observed that the LHRH targeted delivery system could effectively enter drug resistant ovarian cancer cells, and the fate of doxorubicin was tracked with fluorescence microscope. Mild hyperthermia (40°C) generated by IONPs under exposure to AMF synergistically increased the cytotoxicity of doxorubicin delivered by the developed nanocarrier to cancer cells. Thus, the developed IONPs-based delivery system has high potential in the effective treatment of ovarian cancer by combinatorial approach. Copyright © 2013 Elsevier B.V. All rights reserved.

Revisiting the role of radiation treatment for non-serous subtypes of epithelial ovarian cancer.

PubMed

Thomas, G

2013-01-01

Except for its palliative use, radiation has been largely abandoned in the management of ovarian cancers because of the recognized efficacy of chemotherapy agents. Whole abdominal irradiation (WAR), however, has been shown to be of adjuvant and curative value in ovarian cancer with microscopic or minimal residual disease in the pelvis, the so-called "intermediate risk group." Recent hypothesis generating data from the use of adjuvant radiation following adjuvant chemotherapy in ovarian cancer has shown an incremental survival benefit for the rarer non-serous ovarian subtypes including clear cell, endometrioid, and mucinous. No incremental benefit was observed for the more common serous subtype. A retrospective examination of early trials using WAR as the sole postoperative treatment in ovarian cancer has determined that the majority of patients in these studies and cured by radiation actually had the non-serous subtypes. The recognition that the non-serous subtypes differ from the serous cancers in their stage of presentation, their molecular characteristics, their response to classic chemotherapy, and their outcomes suggest the non-serous subtypes should be treated as rare and different cancers. In addition to specific targeting therapies that may be developed, radiation should be reconsidered as part of the treatment armamentarium for these diseases.

Effects of nerve growth factor (NGF) on blood vessels area and expression of the angiogenic factors VEGF and TGFbeta1 in the rat ovary

PubMed Central

Julio-Pieper, Marcela; Lara, Hernán E; Bravo, Javier A; Romero, Carmen

2006-01-01

Background Angiogenesis is a crucial process in follicular development and luteogenesis. The nerve growth factor (NGF) promotes angiogenesis in various tissues. An impaired production of this neurotrophin has been associated with delayed wound healing. A variety of ovarian functions are regulated by NGF, but its effects on ovarian angiogenesis remain unknown. The aim of this study was to elucidate if NGF modulates 1) the amount of follicular blood vessels and 2) ovarian expression of two angiogenic factors: vascular endothelial growth factor (VEGF) and transforming growth factor beta 1 (TGFbeta1), in the rat ovary. Results In cultured neonatal rat ovaries, NGF increased VEGF mRNA and protein levels, whereas TGFbeta1 expression did not change. Sectioning of the superior ovarian nerve, which increases ovarian NGF protein content, augmented VEGF immunoreactivity and the area of capillary vessels in ovaries of prepubertal rats compared to control ovaries. Conclusion Results indicate that NGF may be important in the maintenance of the follicular and luteal vasculature in adult rodents, either indirectly, by increasing the expression of VEGF in the ovary, or directly via promoting the proliferation of vascular cells. This data suggests that a disruption on NGF regulation could be a component in ovarian disorders related with impaired angiogenesis. PMID:17096853

Synthetic PEG Hydrogel for Engineering the Environment of Ovarian Follicles.

PubMed

Mendez, Uziel; Zhou, Hong; Shikanov, Ariella

2018-01-01

The functional unit within the ovary is the ovarian follicle, which is also a morphological unit composed of three basic cell types: the oocyte, granulosa, and theca cells. Similar to human ovarian follicles, mouse follicles can be isolated from their ovarian environment and cultured in vitro to study folliculogenesis, or follicle development for days or weeks. Over the course of the last decade, follicle culture in a three-dimensional (3D) environment exponentially improved the outcomes of in vitro folliculogenesis. Follicle culture in 3D environments preserves follicle architecture and promotes the cross talk between cells in the follicle. Hydrogels, such as polyethylene glycol (PEG), have been used for various physiological systems for regenerative purposes because they provide a 3D environment similar to soft tissues, allow diffusion of nutrients, and can be readily modified to present biological signals, including cell adhesion ligands and proteolytic degradation facilitated by enzymes secreted by the encapsulated cells. This chapter outlines the application of PEG hydrogels to the follicle culture, including the procedures to isolate, encapsulate, and culture mouse ovarian follicles. The tunable properties of PEG hydrogels support co-encapsulation of ovarian follicles with somatic cells, which further promote follicle survival and growth in vitro through paracrine and juxtacrine interactions.

Rationale for eliminating the hormone-free interval in modern oral contraceptives.

PubMed

London, Andrew; Jensen, Jeffrey T

2016-07-01

Although most low-dose combined oral contraceptives (COCs) include 7-day hormone-free intervals (HFIs), these COCs could incompletely suppress ovarian activity. To review the impact of HFIs on ovarian suppression and tolerability, and evaluate the utility of COCs without traditional 7-day HFIs. PubMed was searched for clinical studies published in English between January 1980 and April 2015 on the impact of HFIs and HFI modifications in COCs. Articles assessing contraceptive efficacy or tolerability as the primary focus were included. Abstracts of 319 articles were screened. Analysis of the 161 articles selected revealed that suppression of ovarian activity with low-dose COCs with 7-day HFIs is suboptimal. Loss of ovarian suppression during 7-day HFIs is commonly associated with follicular development, and most dominant follicles appear during this period. By contrast, increased ovarian suppression was noted in regimens that shortened or eliminated the HFI, or that substituted low-dose ethinyl estradiol for the HFI. Extended regimens with modified HFIs may provide greater ovarian suppression with the potential for increased contraceptive effectiveness. Additional research is needed to evaluate whether COC regimens that include 10μg ethinyl estradiol instead of an HFI may improve tolerability. Copyright © 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Potential Role of Estrogen Receptor Beta as a Tumor Suppressor of Epithelial Ovarian Cancer

PubMed Central

Gaudin, Françoise; Machelon, Véronique; Brigitte, Madly; Jacquard, Carine; Pillon, Arnaud; Balaguer, Patrick; Balabanian, Karl; Lazennec, Gwendal

2012-01-01

Ovarian cancer is the gynecological cancer exhibiting the highest morbidity and improvement of treatments is still required. Previous studies have shown that Estrogen-receptor beta (ERβ) levels decreased along with ovarian carcinogenesis. Here, we present evidence that reintroduction of ERβ in BG-1 epithelial ovarian cancer cells, which express ERα, leads in vitro to a decrease of basal and estradiol-promoted cell proliferation. ERβ reduced the frequency of cells in S phase and increased the one of cells in G2/M phase. At the molecular level, we found that ERβ downregulated total retinoblastoma (Rb), phosphorylated Rb and phospho-AKT cellular content as well as cyclins D1 and A2. In addition, ERβ had a direct effect on ERα, by strongly inhibiting its expression and activity, which could explain part of the anti-proliferative action of ERβ. By developing a novel preclinical model of ovarian cancer based on a luminescent orthotopic xenograft in athymic Nude mice, we further revealed that ERβ expression reduces tumor growth and the presence of tumor cells in sites of metastasis, hence resulting in improved survival of mice. Altogether, these findings unveil a potential tumor-suppressor role of ERβ in ovarian carcinogenesis, which could be of potential clinical relevance for the selection of the most appropriate treatment for patients. PMID:22970307

Overt leptin response to controlled ovarian hyperstimulation negatively correlates with pregnancy outcome in in vitro fertilization--embryo transfer cycle.

PubMed

Chakrabarti, Jana; Chatterjee, Ratna; Goswami, Sourendrakanta; Chakravarty, Baidyanath; Kabir, Syed Nazrul

2012-05-01

A critical body mass of adipose tissue is essential for the normal development of female reproductive functions. Leptin, an adipocyte-derived hormone encoded by the 'Ob' gene has been proposed as a peripheral signal indicating the adequacy of nutritional status for reproductive functions. It is reported as a direct regulator of gametogenic and steroidogenic potential of ovary. Though leptin is widely present in reproductive tissues, its relationship to reproductive hormones is still poorly understood. Present investigation attempts to explore ovarian response to secretory profile of leptin and its impact on pregnancy outcome in women undergoing controlled ovarian hyperstimulation for in vitro fertilization and embryo transfer (IVF-ET). Patients enrolled for IVF-ET underwent pituitary-ovarian suppression by 'Long Protocol' GnRH-agonist downregulation followed by ovarian stimulation. Sera were procured at different phases of IVF-ET for the assay of estradiol, progesterone, human chorionic gonadotropin, and for leptin. Ovarian follicular fluids were also assayed for leptin. Luteinized granulosa cells were cultured in vitro to evaluate their steroidogenic potential. Statistical analyses were done by student's t-test, ANOVA, and Chi-square tests as applicable. All results were expressed as Mean ± SE. P values < 0.05 were considered significant. Positive correlation was observed between serum and ovarian follicular fluid leptin. A negative correlation was noted between the serum leptin levels and endometrial thickness. Elevated leptin response may exert adverse impacts on pregnancy success during IVF-ET possibly by modulating uterine receptivity.

A new heterozygous mutation of the FOXL2 gene is associated with a large ovarian cyst and ovarian dysfunction in an adolescent girl with blepharophimosis/ptosis/epicanthus inversus syndrome.

PubMed

Raile, K; Stobbe, H; Tröbs, R B; Kiess, W; Pfäffle, R

2005-09-01

Blepharophimosis/ptosis/epicanthus inversus syndrome (BPES), an autosomal dominant syndrome in which eyelid malformation is associated with (type I BPES) or without premature ovarian failure (type II BPES). Mutations of a putative winged helix/forkhead transcription factor FOXL2 account for both types of BPES. We report on a 16-year-old adolescent girl with blepharophimosis and ptosis. Subsequently she developed oligomenorrhea, secondary amenorrhea for 6 months, and an extremely large cyst of one ovary. The cyst contained 8 l of cyst fluid and histopathology displayed a large corpus luteum cyst. Following laparotomy, gonadotropin levels were elevated (LH 17.2 U/l, FSH 29.4 U/l) and estradiol levels decreased (67 pmol/l). Because of clinical aspects of BPES and abnormal ovarian function we suspected a mutation of her FOXL2 gene and found a new in-frame mutation (904_939dup36) on one allele, leading to a 12 alanine expansion within the polyalanine domain. We conclude that the FOXL2 mutation 904_939dup36 may account not only for blepharophimosis and ptosis but also for ovarian dysfunction and growth of the large corpus luteum cyst. In contrast to known FOXL2 mutations with polyalanine expansions and association with BPES type II, clinical aspects of our girl may indicate some degree of ovarian dysfunction that might finally lead to BPES type I with premature ovarian failure.

A biological effects monitoring survey of Cardigan Bay using flatfish histopathology, cellular biomarkers and sediment bioassays: findings of the Prince Madog Prize 2003.

PubMed

Lyons, Brett P; Stentiford, Grant D; Bignell, John; Goodsir, Freya; Sivyer, David B; Devlin, Michelle J; Lowe, Dave; Beesley, Amanda; Pascoe, Christine K; Moore, Mike N; Garnacho, Eva

2006-07-01

Cardigan Bay on the western coast of the UK is considered a pristine location with much of its coastal and marine habitats protected under various national and EC Directives. Despite this, populations of the flatfish dab (Limanda limanda) captured from Cardigan Bay display elevated levels of liver tumours relative to the background prevalence of the disease. This study describes the findings of a research cruise that took place during November 2003 to assess the prevalence of tumours in dab from selected sites in and around Cardigan Bay. In addition, potential causative mechanisms were investigated via measurement of a range of end points (including composition and abundance of benthic and phytoplankton communities, sediment toxicity and cellular biomarkers of genotoxicity) from sediment, water and biota samples. Fish captured from South Cardigan Bay displayed a relatively higher prevalence of liver tumours compared to those captured from Red Wharf Bay. Hepatocellular adenoma (8% and 2%, respectively) and hepatocellular foci of cell alteration (18% and 6%, respectively) were most prevalent in South Cardigan Bay. Analysis of the sediment failed to distinguish any differences in toxicity between the two sampling sites. However, DNA strand breaks in red blood cells of dab were significantly higher (p < 0.05) in fish collected from Red Warf Bay compared with those sampled at Cardigan Bay. The alignment of biological effects measures via such integrated cruise programs are discussed. This work was partly funded under the auspices of the 2003 Prince Madog Prize.

Enhanced expression of peroxisome proliferator-activated receptor gamma in epithelial ovarian carcinoma.

PubMed

Zhang, G Y; Ahmed, N; Riley, C; Oliva, K; Barker, G; Quinn, M A; Rice, G E

2005-01-17

The peroxisome proliferator-activated receptors (PPARs) belong to a subclass of nuclear hormone receptor that executes important cellular transcriptional functions. Previous studies have demonstrated the expression of PPARgamma in several tumours including colon, breast, bladder, prostate, lung and stomach. This study demonstrates the relative expression of PPARgamma in normal ovaries and different pathological grades of ovarian tumours of serous, mucinous, endometrioid, clear cell and mixed subtypes. A total of 56 ovarian specimens including 10 normal, eight benign, 10 borderline, seven grade 1, nine grade 2 and 12 grade 3 were analysed using immunohistochemistry. Immunoreactive PPARgamma was not expressed in normal ovaries. Out of eight benign and 10 borderline tumours, only one tumour in each group showed weak cytoplasmic PPARgamma expression. In contrast, 26 out of 28 carcinomas studied were positive for PPARgamma expression with staining confined to cytoplasmic and nuclear regions. An altered staining pattern of PPARgamma was observed in high-grade ovarian tumours with PPARgamma being mostly localized in the nuclei with little cytoplasmic immunoreactivity. On the other hand, predominant cytoplasmic staining was observed in lower-grade tumours. Significantly increased PPARgamma immunoreactivity was observed in malignant ovarian tumours (grade 1, 2 and 3) compared to benign and borderline tumours (chi2 = 48.80, P < 0.001). Western blot analyses showed significant elevation in the expression of immunoreactive PPARgamma in grade 3 ovarian tumours compared with that of normal ovaries and benign ovarian tumours (P < 0.01). These findings suggest an involvement of PPARgamma in the onset and development of ovarian carcinoma and provide an insight into the regulation of this molecule in the progression of the disease.

Bilateral Salpingo-Oophorectomy Versus GnRH Analogue in the Adjuvant Treatment of Premenopausal Breast Cancer Patients: Cost-Effectiveness Evaluation of Breast Cancer Outcome, Ovarian Cancer Prevention and Treatment.

PubMed

Ferrandina, Gabriella; Amadio, Giulia; Marcellusi, Andrea; Azzolini, Elena; Puggina, Anna; Pastorino, Roberta; Ricciardi, Walter; Scambia, Giovanni

2017-11-01

BACKGROUND AND OBJECTIVE: There is no available evidence to recommend gonadotropin-releasing hormone (GnRH) analogue-based ovarian suppression versus bilateral salpingo-oophorectomy (BSO) in the adjuvant treatment of early breast cancer, since the two approaches are considered equivalent in terms of oncologic outcome. The role of surgical ovarian ablation has been revitalized based on the advances of minimally invasive surgery, and a better understanding of clinical and molecular basis of hereditary breast/ovarian cancer syndromes. The aim of this study is to analyze the cost-effectiveness of laparoscopic BSO and GnRH analogue administration in patients aged 40-49 years with hormone-sensitive breast cancer. A probabilistic decision tree model was developed to evaluate costs and outcomes of ovarian ablation through laparoscopic BSO, or ovarian suppression through monthly injections of GnRH analogue. Results were expressed as incremental costs per quality-adjusted life years (QALYs) gained. Laparoscopic BSO strategy was associated with a lower mean total cost per patient than GnRH treatment, and considering the difference in terms of QALYs, the incremental effectiveness did not demonstrate a notable difference between the two approaches. From the National Health Service perspective, and for a time horizon of 5 years, laparoscopic BSO was the dominant option compared to GnRH treatment; laparoscopic BSO was less expensive than GnRH, €2385 [95% confidence interval (CI) = 2044, 2753] vs €7093 (95% CI = 3409, 12,105), respectively, and more effective. Surgical ovarian ablation is more cost-effective than GnRH administration in the adjuvant treatment of hormone-sensitive breast cancer patients aged 40-49 years, and the advantage of preventing ovarian cancer through laparoscopic BSO should be considered.

Natural history of autoimmune primary ovarian insufficiency in patients with Addison's disease: from normal ovarian function to overt ovarian dysfunction.

PubMed

De Bellis, Annamaria; Bellastella, Giuseppe; Falorni, Alberto; Aitella, Ernesto; Barrasso, Mariluce; Maiorino, Maria Ida; Bizzarro, Elio; Bellastella, Antonio; Giugliano, Dario; Esposito, Katherine

2017-10-01

Women with autoimmune Addison's disease with normal ovulatory cycles but positive for steroid cell antibodies (StCA) have been considered at risk of premature ovarian insufficiency (POI). Thirty-three women younger than 40 years, with subclinical-clinical autoimmune Addison's disease but with normally ovulatory menses, were followed up for 10 years to evaluate the long-term time-related variations of StCA, ovarian function and follicular reserve. All patients and 27 control women were investigated at the start and every year for the presence and titre of StCA (by indirect immunofluorescence), serum concentrations of anti-Mullerian hormone (AMH) and ovarian function at four consecutive menses every year. At the start of the study StCA were present in 16 women (group 1), at low/middle titres (≤1:32) in seven of them (43.8%, group 1A), at high titres (>1:32) in the remaining nine patients (group 1B, 56.2%), while they were absent from 17 patients (group 2). During the follow-up period, all women in group 1A remained StCA-positive at low/middle titres with normal ovulatory menses and normal gonadotrophin and AMH levels, while all patients in group 1B showed a further increase of StCA titres (1:128-1:256) and progressed through three stages of ovarian function. None of the patients in group 2 and controls showed the appearance of StCA or ovarian dysfunction during the follow-up. The presence of StCA at high titres can be considered a good predictive marker of subsequent development of autoimmune POI. To single out the stages of autoimmune POI may allow a timely therapeutic choice in the subclinical and early clinical stages. © 2017 European Society of Endocrinology.

Obesity and risk of ovarian cancer subtypes: evidence from the Ovarian Cancer Association Consortium.

PubMed

Olsen, Catherine M; Nagle, Christina M; Whiteman, David C; Ness, Roberta; Pearce, Celeste Leigh; Pike, Malcolm C; Rossing, Mary Anne; Terry, Kathryn L; Wu, Anna H; Risch, Harvey A; Yu, Herbert; Doherty, Jennifer A; Chang-Claude, Jenny; Hein, Rebecca; Nickels, Stefan; Wang-Gohrke, Shan; Goodman, Marc T; Carney, Michael E; Matsuno, Rayna K; Lurie, Galina; Moysich, Kirsten; Kjaer, Susanne K; Jensen, Allan; Hogdall, Estrid; Goode, Ellen L; Fridley, Brooke L; Vierkant, Robert A; Larson, Melissa C; Schildkraut, Joellen; Hoyo, Cathrine; Moorman, Patricia; Weber, Rachel P; Cramer, Daniel W; Vitonis, Allison F; Bandera, Elisa V; Olson, Sara H; Rodriguez-Rodriguez, Lorna; King, Melony; Brinton, Louise A; Yang, Hannah; Garcia-Closas, Montserrat; Lissowska, Jolanta; Anton-Culver, Hoda; Ziogas, Argyrios; Gayther, Simon A; Ramus, Susan J; Menon, Usha; Gentry-Maharaj, Aleksandra; Webb, Penelope M

2013-04-01

Whilst previous studies have reported that higher BMI increases a woman's risk of developing ovarian cancer, associations for the different histological subtypes have not been well defined. As the prevalence of obesity has increased dramatically, and classification of ovarian histology has improved in the last decade, we sought to examine the association in a pooled analysis of recent studies participating in the Ovarian Cancer Association Consortium. We evaluated the association between BMI (recent, maximum and in young adulthood) and ovarian cancer risk using original data from 15 case-control studies (13 548 cases and 17 913 controls). We combined study-specific adjusted odds ratios (ORs) using a random-effects model. We further examined the associations by histological subtype, menopausal status and post-menopausal hormone use. High BMI (all time-points) was associated with increased risk. This was most pronounced for borderline serous (recent BMI: pooled OR=1.24 per 5 kg/m(2); 95% CI 1.18-1.30), invasive endometrioid (1.17; 1.11-1.23) and invasive mucinous (1.19; 1.06-1.32) tumours. There was no association with serous invasive cancer overall (0.98; 0.94-1.02), but increased risks for low-grade serous invasive tumours (1.13, 1.03-1.25) and in pre-menopausal women (1.11; 1.04-1.18). Among post-menopausal women, the associations did not differ between hormone replacement therapy users and non-users. Whilst obesity appears to increase risk of the less common histological subtypes of ovarian cancer, it does not increase risk of high-grade invasive serous cancers, and reducing BMI is therefore unlikely to prevent the majority of ovarian cancer deaths. Other modifiable factors must be identified to control this disease.

Lysyl oxidase interacts with AGE signalling to modulate collagen synthesis in polycystic ovarian tissue

PubMed Central

Papachroni, Katerina K; Piperi, Christina; Levidou, Georgia; Korkolopoulou, Penelope; Pawelczyk, Leszek; Diamanti-Kandarakis, Evanthia; Papavassiliou, Athanasios G

2010-01-01

Abstract Connective tissue components – collagen types I, III and IV – surrounding the ovarian follicles undergo drastic changes during ovulation. Abnormal collagen synthesis and increased volume and density of ovarian stroma characterize the polycystic ovary syndrome (PCOS). During the ovulatory process, collagen synthesis is regulated by prolyl hydroxylase and lysyl oxidase (LOX) activity in ovarian follicles. LOX catalyzes collagen and elastin cross-linking and plays essential role in coordinating the control of ovarian extracellular matrix (ECM) during follicular development. We have recently shown accumulation of advanced glycation end products (AGEs), molecules that stimulate ECM production and abnormal collagen cross-linking, in ovarian tissue. However, the possible link between LOX and AGEs-induced signalling in collagen production and stroma formation in ovarian tissue from PCOS remains elusive. The present study investigates the hypothesis of AGE signalling pathway interaction with LOX gene activity in polycystic ovarian (PCO) tissue. We show an increased distribution and co-localization of LOX, collagen type IV and AGE molecules in the PCO tissue compared to control, as well as augmented expression of AGE signalling mediators/effectors, phospho(p)-ERK, phospho(p)-c-Jun and nuclear factor κB (NF-κB) in pathological tissue. Moreover, we demonstrate binding of AGE-induced transcription factors, NF-κB and activator protein-1 (AP-1) on LOX promoter, indicating a possible involvement of AGEs in LOX gene regulation, which may account for the documented increase in LOX mRNA and protein levels compared to control. These findings suggest that deposition of excess collagen in PCO tissue that induces cystogenesis may, in part, be due to AGE-mediated stimulation of LOX activity. PMID:19583806

Epigenetic alteration of p16 and retinoic acid receptor beta genes in the development of epithelial ovarian carcinoma.

PubMed

Bhagat, Rahul; Kumar, Sandeep Sriram; Vaderhobli, Shilpa; Premalata, Chennagiri S; Pallavi, Venkateshaiah Reddihalli; Ramesh, Gawari; Krishnamoorthy, Lakshmi

2014-09-01

Silencing of tumor suppressor and tumor-related genes by promoter hypermethylation is one of the major events in ovarian carcinogenesis. In this study, we analyzed aberrant promoter methylation of p16 and RAR-β genes in 134 epithelial ovarian carcinomas (EOCs), 23 low malignant potential (LMP) tumors, 26 benign cystadenomas, and 15 normal ovarian tissues. Methylation was investigated by methylation-specific PCR (MSP), and the results were confirmed by bisulfite DNA sequencing. Relative gene expression of p16 and RAR-β was done using quantitative reverse transcriptase PCR (qRT-PCR) on 51 EOC cases, 9 LMP tumors, and 7 benign cystadenomas with 5 normal ovarian tissues. Aberrant methylation for p16 and RAR-β was present in 43 % (58/134) and 31 % (41/134) in carcinoma cases, 22 % (05/23) and 52 % (12/23) in LMP tumors, and 42 % (11/26) and 69 % (18/26) in benign cystadenomas. No methylation was observed in any of the normal ovarian tissues. The mRNA expression level of p16 and RAR-β was significantly downregulated in EOC and LMP tumors than the corresponding normal tissues whereas the expression level was normal in benign cystadenomas for p16 and slightly reduced for RAR-β. A significant correlation of p16 promoter methylation was observed with reduced gene expression in EOC. For RAR-β, no significant correlation was observed between promoter methylation and gene expression. Our results suggest that epigenetic alterations of p16 and RAR-β have an important role in ovarian carcinogenesis and that mechanism along with methylation plays a significant role in downregulation of RAR-β gene in ovarian cancer.

Ovarian morphology and function during growth hormone therapy of short girls born small for gestational age.

PubMed

Tinggaard, Jeanette; Jensen, Rikke Beck; Sundberg, Karin; Birkebæk, Niels; Christiansen, Peter; Ellermann, Annie; Holm, Kirsten; Jeppesen, Eva Mosfeldt; Kremke, Britta; Marcinski, Pawel; Pedersen, Carsten; Saurbrey, Nina; Thisted, Ebbe; Main, Katharina M; Juul, Anders

2014-12-01

To study the effect of growth hormone (GH) treatment on ovarian and uterine morphology and function in short, prepubertal small-for-gestational-age (SGA) girls. A multinational, randomized controlled trial on safety and efficacy of GH therapy in short, prepubertal children born SGA. Not applicable. A subgroup of 18 Danish girls born SGA included in North European SGA Study (NESGAS). One year of GH treatment (67 μg/kg/day) followed by 2 years of randomized GH treatment (67 μg/kg/day, 35 μg/kg/day, or IGF-I titrated). Data on anthropometrics, reproductive hormones, and ultrasonographic examination of the internal genitalia were collected during 36 months of GH treatment. Uterine and ovarian volume increased significantly during 3 years of treatment (64% and 110%, respectively) but remained low within normal reference ranges. Ovarian follicles became visible in 58% after 1 year compared with 28% before GH therapy. Anti-Müllerian hormone increased significantly during the 3 years of GH therapy but remained within the normal range. Precocious puberty was observed in one girl; another girl developed multicystic ovaries. GH treatment was associated with statistically significant growth of the internal genitalia, but remained within the normal range. As altered pubertal development and ovarian morphology were found in 2 of 18 girls, monitoring of puberty and ovarian function during GH therapy in SGA girls is prudent. Altogether, the findings are reassuring. However, long-term effects of GH treatment on adult reproductive function remain unknown. EudraCT 2005-001507-19. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Association of basal serum androgen levels with ovarian response and ICSI cycle outcome.

PubMed

Abide Yayla, C; Ozkaya, E; Kayatas Eser, S; Sanverdi, I; Devranoglu, B; Kutlu, T

2018-05-01

The purpose of this study was to assess the predictive value of basal serum testosterone (T) and dehydroepiandrosterone sulfate (DHEAS) levels during follicular phase for ovarian response and outcome in intracytoplasmic sperm injection (ICSI) cycles of women with diminished ovarian reserve. We prospectively gathered data of basal serum androgen levels and ICSI cycle characteristics of 120 women with diminished ovarian reserve. Association of basal serum T and DHEAS levels with ovarian response was analyzed. Basal T and DHEAS levels were similar between pregnant and non-pregnant cases (P > 0.05). There were significant differences between groups with and without successful embryo implantation in terms of serum follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH), gonadotropin starting and total dose, and peak estradiol level (P < 0.05). There were 58 (49.2%) cases who did not reach to the embryo transfer stage due to several reasons including cancelation of stimulation due to unresponsiveness (n = 26, 21.7%), no oocyte at oocyte pickup (n = 11, 9.2%), no mature oocyte (n = 6, 5%), and failure of fertilization or embryo development (n = 15, 12.5%). Basal androgen levels were not significant predictors for any of the cycle outcome. AMH level was a significant predictor for failure of fertilization or embryo development (AUC 0.722, P = 0.01) and cancelation of stimulation (AUC 0.801, P < 0.001). FSH was a significant predictor for cancelation of stimulation (AUC 0.774, P < 0.001). In women with diminished ovarian reserve, basal T and DHEAS levels have no value in predicting any of the cycle outcome parameters.

Alterations in expression pattern of splicing factors in epithelial ovarian cancer and its clinical impact.

PubMed

Iborra, Severine; Hirschfeld, Marc; Jaeger, Markus; Zur Hausen, Axel; Braicu, Iona; Sehouli, Jalid; Gitsch, Gerald; Stickeler, Elmar

2013-07-01

Alternative splicing represents an important nuclear mechanism in the posttranscriptional regulation of gene expression, which is frequently altered during tumorigenesis. Previously, we described marked changes in alternative splicing of the CD44 gene in ovarian and breast cancer as well as specific induction of distinct splicing factors during tumor development. The present study was focused on the expression profiles of different splicing factors, including classical serine-arginine (SR) proteins including ASF/SF2, hTra2β1, hTra2α, and Y-box-binding protein (YB-1) in physiological and malignant epithelial ovarian tissue to evaluate their expression pattern with regard to tumor development and disease progression. Expression levels of the different splicing factors were analyzed in physiological epithelial ovarian tissue samples, primary tumors, and metastatic samples of patients with a diagnosis of epithelial ovarian cancer using quantified reverse transcription polymerase chain reaction analysis. We examined more closely the splicing factor hTra2β1 using Western blot analysis and immunohistochemistry. The analysis revealed a marked and specific induction of ASF/SF2, SRp20, hTra2β1, and YB-1 in primary tumors as well as in their metastatic sites. However, in our patient cohort, no induction was seen for the other investigated splicing factors SRp55, SRp40, and hTra2α. Our results suggest a specific induction of distinct splicing factors in ovarian cancer tumorigenesis. The involvement of hTra2β1, YB-1, SRp20, and ASF/SF2 in exon recognition and alternative splicing may be important for gene regulation of alternatively spliced genes like CD44 with potential functional consequences in this tumor type leading to progression and metastasis.

Targeted Ovarian Cancer Education for Hispanic Women: A Pilot Program in Arizona.

PubMed

Schlumbrecht, Matthew; Yarian, Ranay; Salmon, Kristine; Niven, Christine; Singh, Diljeet

2016-06-01

In disadvantaged populations, including Hispanics, there is a deficit in understanding of cancer risk factors, symptoms, prevention, and treatment. The objective of this study was to assess ovarian cancer knowledge in a population of Hispanic women in Arizona, identify deficiencies, and to evaluate the utility of an educational program developed specifically for this community's needs. A de novo questionnaire about ovarian cancer was distributed to Hispanic women enrolled in family literacy programs at Mesa Public Schools. Following this assessment, a video educational program was developed, with emphasis on areas of greatest knowledge deficits, and post-intervention assessment administered. Chi square, Wilcoxon rank sum, and Kruskal-Wallis tests were used for analysis. 167 questionnaires were completed in the pretest group and 102 in the post-intervention group. Between groups, there were no differences in age (p = 0.49), education (p = 0.68), or annual income (p = 0.26). In the pretest group, 45 % of questions were answered correctly versus 84 % in the post-test group (p < 0.01). 24.2 % of the initial respondents correctly identified ovarian cancer symptoms versus 85.6 of post-test respondents (p < 0.01). With the program, there was an increase in the number of correct post-test responses for each question and symptom (p < 0.01), except those about hereditary risk of ovarian cancer (p = 0.62) and pelvic anatomy (p = 0.16). Following identification of an ovarian cancer knowledge deficit in this cohort of Hispanic women, an educational tool targeting specific deficiencies successfully increased cancer knowledge and awareness of symptoms. Similar efforts in this and other minority populations should be continued.

In vitro high throughput phage display selection of ovarian cancer avid phage clones for near-infrared optical imaging.

PubMed

Soendergaard, Mette; Newton-Northup, Jessica R; Deutscher, Susan L

2014-01-01

Ovarian cancer is among the leading causes of cancer deaths in women, and is the most fatal gynecological malignancy. Poor outcomes of the disease are a direct result of inadequate detection and diagnostic methods, which may be overcome by the development of novel efficacious screening modalities. However, the advancement of such technologies is often time-consuming and costly. To overcome this hurdle, our laboratory has established a time and cost effective method of selecting and identifying ovarian carcinoma avid bacteriophage (phage) clones using high throughput phage display technology. These phage clones were selected from a filamentous phage fusion vector (fUSE5) 15-amino acid peptide library against human ovarian carcinoma (SKOV-3) cells, and identified by DNA sequencing. Two phage clones, pM6 and pM9, were shown to exhibit high binding affinity and specificity for SKOV-3 cells using micropanning, cell binding and fluorescent microscopy studies. To validate that the binding was mediated by the phage-displayed peptides, biotinylated peptides (M6 and M9) were synthesized and the specificity for ovarian carcinoma cells was analyzed. These results showed that M6 and M9 bound to SKOV-3 cells in a dose-response manner and exhibited EC50 values of 22.9 ± 2.0 μM and 12.2 ± 2.1μM (mean ± STD), respectively. Based on this, phage clones pM6 and pM9 were labeled with the near-infrared fluorophore AF680, and examined for their pharmacokinetic properties and tumor imaging abilities in vivo. Both phage successfully targeted and imaged SKOV-3 tumors in xenografted nude mice, demonstrating the ability of this method to quickly and cost effectively develop novel ovarian carcinoma avid phage.

Gene expression during ovarian differentiation in parasitic and non-parasitic lampreys: implications for fecundity and life history types.

PubMed

Spice, Erin K; Whyard, Steven; Docker, Margaret F

2014-11-01

Lampreys diverged from the jawed vertebrate lineage approximately 500million years ago. Lampreys undergo sex differentiation much later than most other vertebrates, and ovarian differentiation occurs several years before testicular differentiation. The genetic basis of lamprey sex differentiation is of particular interest both because of the phylogenetic importance of lampreys and because of their unusual pattern of sex differentiation. As well, differences between parasitic and non-parasitic lampreys may first become evident at ovarian differentiation. However, nothing is known about the genetic basis of ovarian differentiation in lampreys. This study examined potential differences in gene expression before, during, and after ovarian differentiation in parasitic chestnut lamprey Ichthyomyzon castaneus and non-parasitic northern brook lamprey Ichthyomyzonfossor. Eight target genes (17β-hydroxysteroid dehydrogenase, germ cell-less, estrogen receptor β, insulin-like growth factor 1 receptor, daz-associated protein 1, cytochrome c oxidase subunit III, Wilms' tumour suppressor protein 1, and dehydrocholesterol reductase 7) were examined. Northern brook lamprey displayed higher expression of cytochrome c oxidase subunit III, whereas chestnut lamprey displayed higher expression of insulin-like growth factor 1 receptor; these genes may be involved in apoptosis and oocyte growth, respectively. Presumptive male larvae had higher expression of Wilms' tumour suppressor protein 1, which may be involved in the undifferentiated gonad and/or later testicular development. Differentiated females had higher expression of 17β hydroxysteroid dehydrogenase and daz-associated protein 1, which may be involved in female development. This study is the first to identify genes that may be involved in ovarian differentiation and fecundity in lampreys. Copyright © 2014 Elsevier Inc. All rights reserved.

Peroxisome proliferator-activated receptor-gamma agonist rosiglitazone reverses the adverse effects of diet-induced obesity on oocyte quality.

PubMed

Minge, Cadence E; Bennett, Brenton D; Norman, Robert J; Robker, Rebecca L

2008-05-01

Obesity and its physiological consequences are increasingly prevalent among women of reproductive age and are associated with infertility. To investigate, female mice were fed a high-fat diet until the onset of insulin resistance, followed by assessments of ovarian gene expression, ovulation, fertilization, and oocyte developmental competence. We report defects to ovarian function associated with diet-induced obesity (DIO) that result in poor oocyte quality, subsequently reduced blastocyst survival rates, and abnormal embryonic cellular differentiation. To identify critical cellular mediators of ovarian responses to obesity induced insulin resistance, DIO females were treated for 4 d before mating with an insulin-sensitizing pharmaceutical: glucose and lipid-lowering AMP kinase activator, 5-aminoimidazole 4-carboxamide-riboside, 30 mg/kg.d; sodium salicylate, IkappaK inhibitor that reverses insulin resistance, 50 mg/kg.d; or peroxisome proliferator activated receptor-gamma agonist rosiglitazone, 10 mg/kg.d. 5-aminoimidazole 4-carboxamide-riboside or sodium salicylate treatment did not have significant effects on the reproductive parameters examined. However, embryonic development to the blastocyst stage was significantly improved when DIO mice were treated with rosiglitazone, effectively repairing development rates. Rosiglitazone also normalized DIO-associated abnormal blastomere allocation to the inner cell mass. Such improvements to oocyte quality were coupled with weight loss, improved glucose metabolism, and changes in ovarian mRNA expression of peroxisome proliferator activated receptor-regulated genes, Cd36, Scarb1, and Fabp4 cholesterol transporters. These studies demonstrate that peri-conception treatment with select insulin-sensitizing pharmaceuticals can directly influence ovarian functions and ultimately exert positive effects on oocyte developmental competence. Improved blastocyst quality in obese females treated with rosiglitazone before mating indicates that peroxisome proliferator activated receptor-gamma is a key target for metabolic regulation of ovarian function and oocyte quality.

Pegylated Liposomal Doxorubicin Hydrochloride, Carboplatin, Veliparib, and Bevacizumab in Treating Patients With Recurrent Ovarian Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer

ClinicalTrials.gov

2017-07-24

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

Vaccine Therapy in Treating Patients With Stage IIIC-IV Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cavity Cancer Following Surgery and Chemotherapy

ClinicalTrials.gov

2017-10-12

Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Tumor; Fallopian Tube Mucinous Neoplasm; Fallopian Tube Serous Neoplasm; Fallopian Tube Transitional Cell Carcinoma; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Transitional Cell Carcinoma; Primary Peritoneal Serous Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

Multiparity activates interferon pathways in peritoneal adipose tissue and decreases susceptibility to ovarian cancer metastasis in a murine allograft model.

PubMed

Loughran, Elizabeth A; Phan, Ryan C; Leonard, Annemarie K; Tarwater, Laura; Asem, Marwa; Liu, Yueying; Yang, Jing; Klymenko, Yuliya; Johnson, Jeff; Shi, Zonggao; Hilliard, Tyvette S; Blumenthaler, Marielle; Leevy, Matthew; Ravosa, Matthew J; Stack, M Sharon

2017-12-28

Ovarian cancer is the fifth leading cause of cancer deaths in U.S. women and the deadliest gynecologic malignancy. This lethality is largely due to the fact that most cases are diagnosed at metastatic stages of the disease when the prognosis is poor. Epidemiologic studies consistently demonstrate that parous women have a reduced risk of developing ovarian cancer, with a greater number of births affording greater protection; however little is known about the impact of parity on ovarian cancer metastasis. Here we report that multiparous mice are less susceptible to ovarian cancer metastasis in an age-matched syngeneic murine allograft model. Interferon pathways were found to be upregulated in healthy adipose tissue of multiparous mice, suggesting a possible mechanism for the multiparous-related protective effect against metastasis. This protective effect was found to be lost with age. Based on this work, future studies exploring therapeutic strategies which harness the multiparity-associated protective effect demonstrated here are warranted. Copyright © 2017. Published by Elsevier B.V.

Automatic classification of ovarian cancer types from cytological images using deep convolutional neural networks.

PubMed

Wu, Miao; Yan, Chuanbo; Liu, Huiqiang; Liu, Qian

2018-06-29

Ovarian cancer is one of the most common gynecologic malignancies. Accurate classification of ovarian cancer types (serous carcinoma, mucous carcinoma, endometrioid carcinoma, transparent cell carcinoma) is an essential part in the different diagnosis. Computer-aided diagnosis (CADx) can provide useful advice for pathologists to determine the diagnosis correctly. In our study, we employed a Deep Convolutional Neural Networks (DCNN) based on AlexNet to automatically classify the different types of ovarian cancers from cytological images. The DCNN consists of five convolutional layers, three max pooling layers, and two full reconnect layers. Then we trained the model by two group input data separately, one was original image data and the other one was augmented image data including image enhancement and image rotation. The testing results are obtained by the method of 10-fold cross-validation, showing that the accuracy of classification models has been improved from 72.76 to 78.20% by using augmented images as training data. The developed scheme was useful for classifying ovarian cancers from cytological images. © 2018 The Author(s).

CXCL12 chemokine genotypes as predictive biomarkers of ovarian cancer outcome.

PubMed

Coelho, Ana; Pereira, Deolinda; Nogal, Ana; Pinto, Daniela; Catarino, Raquel; Araújo, António; Medeiros, Rui

2009-01-01

Ovarian cancer is an aggressive disease with high mortality. The CXCL12 chemokine has been associated with the development of this neoplasia. The aim of this study was to evaluate the genetic influence of the CXCL12-3'A polymorphism as a prognostic/predictive factor in ovarian cancer patients treated with platinum/paclitaxel chemotherapy. The mean survival rates for early stages (I/II) of the disease were statistically different according to patient genotype (96 months for GG and 57 months for A carrier genotypes; p=0.017). The mean progression-free interval was statistically lower in patients with early stages (I/II) of the tumour carrying the A allele (55 months) than in those carrying the GG genotype (91 months; P=0.009). The CXCL12-3'A polymorphism leads to a poorer response to chemotherapy with cisplatin/paclitaxel, and diminishes the mean survival rate and the progression-free interval in patients with ovarian cancer. CXCL12-3'A may therefore serve as an important predictive biomarker for the determination of outcome in ovarian cancer.

Amygdala Kindling Alters Estrus Cycle and Ovarian Morphology in the Rat

PubMed Central

Pan, Juan; Zhang, Lingwu; Wang, Feng; Liu, Dan

2014-01-01

The objective of this study is to explore the effects of amygdala kindling on estrus cycle and ovarian morphology. Thirty-five female rats at the age of 8 weeks were randomly designated to electrode kindled, sham-kindled, and normal controls. Kindled rats were implanted with kindling electrodes in the left basolateral amygdala and kindled by brief suprathreshold stimulations with a bipolar electrode. Estrous cycles were daily monitored through vaginal smears. Electrographic and behavioral seizures were recorded and ovarian morphology was evaluated by light and electron microscopies. Our results showed that the kindled rats lost their ovarian periodicity displayed significant ovarian enlargement. H&E staining revealed increased number of growing follicles and total follicles, as well as polycysts in the ovaries of the kindled animals compared to sham and control animals. Ultrastructural study detected numerous apoptotic granulosa cells in growing follicles and thecal cell hyperplasia with secretary granules in the thecal cells in the kindled rats. The results suggest that amygdala kindling is a risk factor for the development of polycystic ovary syndrome. PMID:25285307