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Sample records for dialogue regulating endometrial

  1. Endocrine and paracrine regulation of endometrial angiogenesis.

    PubMed

    Taylor, R N; Lebovic, D I; Hornung, D; Mueller, M D

    2001-09-01

    The human endometrium is a complex tissue comprised of different cell types, including epithelial, stromal, inflammatory, perivascular, and blood vessel cells. The hormonal receptivity and distribution of these cell populations change during the menstrual cycle. Cyclical endometrial growth is dependent on its ability to regenerate a vascular capillary network, which grows in parallel with the proliferation and differentiation of the endometrial lining. Natural hormonal effects on the endometrium and endocrine manipulation of this tissue, in response to the use of exogenous steroid therapies, can affect endometrial capillary proliferation and function, leading to clinical abnormalities of uterine bleeding. We propose that the regulation of endometrial angiogenesis is mediated indirectly via complex interactions among cell types. Our laboratory has focused on a prototypical member of the angiogenic proteins, vascular endothelial growth factor (VEGF)-A. In this paper we present data demonstrating that VEGF-A expression in normal endometrial epithelial and stromal cells and in Ishikawa adenocarcinoma cells is increased by an ovarian steroid, estradiol. Infiltrating immune cells, particularly polymorphonuclear granulocytes, also are sources of VEGF-A. In inflammatory conditions involving the endometrium (e.g., endometriosis), a proinflammatory cytokine, IL-1beta, can mediate neoangiogenesis by inducing VEGF-A gene transcription. Thus, endometrial vascularization is effected by both endocrine and paracrine pathways. PMID:11594532

  2. miR-200 Regulates Endometrial Development During Early Pregnancy.

    PubMed

    Jimenez, Patricia T; Mainigi, Monica A; Word, R Ann; Kraus, W Lee; Mendelson, Carole R

    2016-09-01

    For successful embryo implantation, endometrial stromal cells must undergo functional and morphological changes, referred to as decidualization. However, the molecular mechanisms that regulate implantation and decidualization are not well defined. Here we demonstrate that the estradiol- and progesterone-regulated microRNA (miR)-200 family was markedly down-regulated in mouse endometrial stromal cells prior to implantation, whereas zinc finger E-box binding homeobox-1 and -2 and other known and predicted targets were up-regulated. Conversely, miR-200 was up-regulated during in vitro decidualization of human endometrial stromal cells. Knockdown of miR-200 negatively affected decidualization and prevented the mesenchymal-epithelial transition-like changes that accompanied decidual differentiation. Notably, superovulation of mice and humans altered miR-200 expression. Our findings suggest that hormonal alterations that accompany superovulation may negatively impact endometrial development and decidualization by causing aberrant miR-200 expression. PMID:27533790

  3. Conceptus-derived prostaglandins regulate endometrial function in sheep.

    PubMed

    Dorniak, Piotr; Bazer, Fuller W; Wu, Guoyao; Spencer, Thomas E

    2012-07-01

    In sheep, the trophectoderm of the elongating conceptus secretes interferon tau (IFNT) and prostaglandins (PGE2, PGF2alpha, PGI2). The PGs are derived from PG synthase 2 (PTGS2), and inhibition of PTGS2 in utero prevents conceptus elongation. IFNT increases expression of many genes in the endometrial epithelia that regulate conceptus elongation. This study tested the hypothesis that PGs secreted by the conceptus regulate endometrial functions that govern conceptus elongation. Cyclic ewes received intrauterine infusions of control vehicle or early pregnancy levels of IFNT, PGE2, PGF2alpha, or PGI2 from Days 10-14 postestrus. Expression levels of endometrial GRP, IGFBP1, and LGALS15, whose products stimulate trophectoderm cell migration and attachment, were increased by PGE2, PGI2, and IFNT. All PGs and IFNT increased expression of the HEXB protease gene, but only IFNT increased the CST6 protease inhibitor gene. Differential effects of PGs were observed for expression of the CTSL protease gene and its inhibitor, CST3. IFNT, PGF2alpha, and PGI2 increased ANGPTL3 expression, but only IFNT and PGE2 increased HIF1A expression, both of which regulate angiogenesis. For glucose transporters, IFNT and all PGs increased SLC2A1 expression, but only PGs increased SLC2A5 expression, whereas endometrial SLC2A12 and SLC5A1 expression levels were increased by IFNT, PGE2, and PGF2alpha. Infusions of all PGs and IFNT increased the amino acid transporter SLC1A5, but only IFNT increased SLC7A2 expression. In the uterine lumen, only IFNT increased glucose levels, and only PGE2 and PGF2alpha increased total amino acids. These results indicate that PGs and IFNT from the conceptus coordinately regulate endometrial functions important for growth and development of the conceptus during the peri-implantation period of pregnancy. PMID:22517622

  4. Rac1 Regulates Endometrial Secretory Function to Control Placental Development.

    PubMed

    Davila, Juanmahel; Laws, Mary J; Kannan, Athilakshmi; Li, Quanxi; Taylor, Robert N; Bagchi, Milan K; Bagchi, Indrani C

    2015-08-01

    During placenta development, a succession of complex molecular and cellular interactions between the maternal endometrium and the developing embryo ensures reproductive success. The precise mechanisms regulating this maternal-fetal crosstalk remain unknown. Our study revealed that the expression of Rac1, a member of the Rho family of GTPases, is markedly elevated in mouse decidua on days 7 and 8 of gestation. To investigate its function in the uterus, we created mice bearing a conditional deletion of the Rac1 gene in uterine stromal cells. Ablation of Rac1 did not affect the formation of the decidua but led to fetal loss in mid gestation accompanied by extensive hemorrhage. To gain insights into the molecular pathways affected by the loss of Rac1, we performed gene expression profiling which revealed that Rac1 signaling regulates the expression of Rab27b, another GTPase that plays a key role in targeting vesicular trafficking. Consequently, the Rac1-null decidual cells failed to secrete vascular endothelial growth factor A, which is a critical regulator of decidual angiogenesis, and insulin-like growth factor binding protein 4, which regulates the bioavailability of insulin-like growth factors that promote proliferation and differentiation of trophoblast cell lineages in the ectoplacental cone. The lack of secretion of these key factors by Rac1-null decidua gave rise to impaired angiogenesis and dysregulated proliferation of trophoblast cells, which in turn results in overexpansion of the trophoblast giant cell lineage and disorganized placenta development. Further experiments revealed that RAC1, the human ortholog of Rac1, regulates the secretory activity of human endometrial stromal cells during decidualization, supporting the concept that this signaling G protein plays a central and conserved role in controlling endometrial secretory function. This study provides unique insights into the molecular mechanisms regulating endometrial secretions that mediate stromal

  5. Rac1 Regulates Endometrial Secretory Function to Control Placental Development

    PubMed Central

    Davila, Juanmahel; Laws, Mary J.; Kannan, Athilakshmi; Li, Quanxi; Taylor, Robert N.; Bagchi, Milan K.; Bagchi, Indrani C.

    2015-01-01

    During placenta development, a succession of complex molecular and cellular interactions between the maternal endometrium and the developing embryo ensures reproductive success. The precise mechanisms regulating this maternal-fetal crosstalk remain unknown. Our study revealed that the expression of Rac1, a member of the Rho family of GTPases, is markedly elevated in mouse decidua on days 7 and 8 of gestation. To investigate its function in the uterus, we created mice bearing a conditional deletion of the Rac1 gene in uterine stromal cells. Ablation of Rac1 did not affect the formation of the decidua but led to fetal loss in mid gestation accompanied by extensive hemorrhage. To gain insights into the molecular pathways affected by the loss of Rac1, we performed gene expression profiling which revealed that Rac1 signaling regulates the expression of Rab27b, another GTPase that plays a key role in targeting vesicular trafficking. Consequently, the Rac1-null decidual cells failed to secrete vascular endothelial growth factor A, which is a critical regulator of decidual angiogenesis, and insulin-like growth factor binding protein 4, which regulates the bioavailability of insulin-like growth factors that promote proliferation and differentiation of trophoblast cell lineages in the ectoplacental cone. The lack of secretion of these key factors by Rac1-null decidua gave rise to impaired angiogenesis and dysregulated proliferation of trophoblast cells, which in turn results in overexpansion of the trophoblast giant cell lineage and disorganized placenta development. Further experiments revealed that RAC1, the human ortholog of Rac1, regulates the secretory activity of human endometrial stromal cells during decidualization, supporting the concept that this signaling G protein plays a central and conserved role in controlling endometrial secretory function. This study provides unique insights into the molecular mechanisms regulating endometrial secretions that mediate stromal

  6. Aromatase expression and regulation in breast and endometrial cancer.

    PubMed

    Zhao, Hong; Zhou, Ling; Shangguan, Anna Junjie; Bulun, Serdar E

    2016-07-01

    Long-term exposure to excess estrogen increases the risk of breast cancer and type 1 endometrial cancer. Most of the estrogen in premenopausal women is synthesized by the ovaries, while extraovarian subcutaneous adipose tissue is the predominant tissue source of estrogen after menopause. Estrogen and its metabolites can cause hyperproliferation and neoplastic transformation of breast and endometrial cells via increased proliferation and DNA damage. Several genetically modified mouse models have been generated to help understand the physiological and pathophysiological roles of aromatase and estrogen in the normal breast and in the development of breast cancers. Aromatase, the key enzyme for estrogen production, is comprised of at least ten partially tissue-selective and alternatively used promoters. These promoters are regulated by distinct signaling pathways to control aromatase expression and estrogen formation via recruitment of various transcription factors to their cis-regulatory elements. A shift in aromatase promoter use from I.4 to I.3/II is responsible for the excess estrogen production seen in fibroblasts surrounding malignant epithelial cells in breast cancers. Targeting these distinct pathways and/or transcription factors to modify aromatase activity may lead to the development of novel therapeutic remedies that inhibit estrogen production in a tissue-specific manner. PMID:27067638

  7. Cortisol regulates the paracrine action of macrophages by inducing vasoactive gene expression in endometrial cells.

    PubMed

    Thiruchelvam, Uma; Maybin, Jacqueline A; Armstrong, Gregory M; Greaves, Erin; Saunders, Philippa T K; Critchley, Hilary O D

    2016-06-01

    The human endometrium undergoes inflammation and tissue repair during menstruation. We hypothesized that the local availability of bioactive glucocorticoids plays an important role in immune cell-vascular cell interactions in endometrium during tissue repair at menstruation, acting either directly or indirectly via tissue resident macrophages. We sought to determine whether endometrial macrophages are direct targets for glucocorticoids; whether cortisol-treated macrophages have a paracrine effect on angiogenic gene expression by endometrial endothelial cells; and whether endometrial macrophages express angiogenic factors. Human endometrium (n = 41) was collected with ethical approval and subject consent. Donor peripheral blood monocyte-derived macrophages were treated with estradiol, progesterone, or cortisol. The effect of peripheral blood monocyte-derived macrophage secretory products on the expression of angiogenic RNAs by endothelial cells was examined. Immunofluorescence was used to examine localization in macrophages and other endometrial cell types across the menstrual cycle. Endometrial macrophages express the glucocorticoid receptor. In vitro culture with supernatants from cortisol-treated peripheral blood monocyte-derived macrophages resulted in altered endometrial endothelial cell expression of the angiogenic genes, CXCL2, CXCL8, CTGF, and VEGFC These data highlight the importance of local cortisol in regulating paracrine actions of macrophages in the endometrium. CXCL2 and CXCL8 were detected in endometrial macrophages in situ. The expression of these factors was highest in the endometrium during the menstrual phase, consistent with these factors having a role in endometrial repair. Our data have indicated that activation of macrophages with glucocorticoids might have paracrine effects by increasing angiogenic factor expression by endometrial endothelial cells. This might reflect possible roles for macrophages in endometrial repair of the vascular bed

  8. Down-regulated expression of transforming growth factor beta 1 mRNA in endometrial carcinoma.

    PubMed Central

    Perlino, E.; Loverro, G.; Maiorano, E.; Giannini, T.; Cazzolla, A.; Napoli, A.; Fiore, M. G.; Ricco, R.; Marra, E.; Selvaggi, L.

    1998-01-01

    Transforming growth factor beta1 (TGF-beta1) is a potent modulator of cell proliferation in vitro, and recent studies have demonstrated its overexpression in several different tumours; nevertheless, the molecular mechanisms of TGF-beta1 action on cell growth and differentiation have not been fully elucidated. To clarify the role of TGF-beta and its receptor in human endometrial proliferation and differentiation, TGF-beta1 expression at both the mRNA and protein levels has been evaluated by using Northern blotting and immunohistochemistry, in both normal (atrophic, proliferative and secretory) and neoplastic (adenocarcinoma) endometrial samples. This study demonstrates that TGF-beta1 mRNA expression is dramatically reduced in endometrial carcinomas with respect to non-neoplastic tissues, whereas the immunohistochemical expression of TGF-beta1 is enhanced in the epithelial component of endometrial carcinomas compared with non-neoplastic tissues. These data suggest that TGF-beta1 acts as a paracrine regulator of endometrial cell proliferation and that it may contribute to the carcinogenic mechanisms of endometrial carcinoma. Images Figure 1 Figure 5 Figure 6 Figure 8 PMID:9579831

  9. Down-regulated expression of transforming growth factor beta 1 mRNA in endometrial carcinoma.

    PubMed

    Perlino, E; Loverro, G; Maiorano, E; Giannini, T; Cazzolla, A; Napoli, A; Fiore, M G; Ricco, R; Marra, E; Selvaggi, L

    1998-04-01

    Transforming growth factor beta1 (TGF-beta1) is a potent modulator of cell proliferation in vitro, and recent studies have demonstrated its overexpression in several different tumours; nevertheless, the molecular mechanisms of TGF-beta1 action on cell growth and differentiation have not been fully elucidated. To clarify the role of TGF-beta and its receptor in human endometrial proliferation and differentiation, TGF-beta1 expression at both the mRNA and protein levels has been evaluated by using Northern blotting and immunohistochemistry, in both normal (atrophic, proliferative and secretory) and neoplastic (adenocarcinoma) endometrial samples. This study demonstrates that TGF-beta1 mRNA expression is dramatically reduced in endometrial carcinomas with respect to non-neoplastic tissues, whereas the immunohistochemical expression of TGF-beta1 is enhanced in the epithelial component of endometrial carcinomas compared with non-neoplastic tissues. These data suggest that TGF-beta1 acts as a paracrine regulator of endometrial cell proliferation and that it may contribute to the carcinogenic mechanisms of endometrial carcinoma. PMID:9579831

  10. REGULATION OF CONCEPTUS ADHESION BY ENDOMETRIAL CXC CHEMOKINES DURING THE IMPLANTATION PERIOD IN SHEEP

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To gain a better understanding of biochemical mechanisms of conceptus adhesion to the maternal endometrium in ruminant ungulates, the present study was performed to clarify roles of chemokines and extracellular matrix (ECM) components in the regulation of ovine blastocyst attachment to the endometri...

  11. Androgens regulate scarless repair of the endometrial "wound" in a mouse model of menstruation.

    PubMed

    Cousins, Fiona L; Kirkwood, Phoebe M; Murray, Alison A; Collins, Frances; Gibson, Douglas A; Saunders, Philippa T K

    2016-08-01

    The human endometrium undergoes regular cycles of synchronous tissue shedding (wounding) and repair that occur during menstruation before estrogen-dependent regeneration. Endometrial repair is normally both rapid and scarless. Androgens regulate cutaneous wound healing, but their role in endometrial repair is unknown. We used a murine model of simulated menses; mice were treated with a single dose of the nonaromatizable androgen dihydrotestosterone (DHT; 200 µg/mouse) to coincide with initiation of tissue breakdown. DHT altered the duration of vaginal bleeding and delayed restoration of the luminal epithelium. Analysis of uterine mRNAs 24 h after administration of DHT identified significant changes in metalloproteinases (Mmp3 and -9; P < 0.01), a snail family member (Snai3; P < 0.001), and osteopontin (Spp1; P < 0.001). Chromatin immunoprecipitation analysis identified putative androgen receptor (AR) binding sites in the proximal promoters of Mmp9, Snai3, and Spp1. Striking spatial and temporal changes in immunoexpression of matrix metalloproteinase (MMP) 3/9 and caspase 3 were detected after DHT treatment. These data represent a paradigm shift in our understanding of the role of androgens in endometrial repair and suggest that androgens may have direct impacts on endometrial tissue integrity. These studies provide evidence that the AR is a potential target for drug therapy to treat conditions associated with aberrant endometrial repair processes.-Cousins, F. L., Kirkwood, P. M., Murray, A. A., Collins, F., Gibson, D. A., Saunders, P. T. K. Androgens regulate scarless repair of the endometrial "wound" in a mouse model of menstruation. PMID:27121597

  12. National policy dialogue on state and federal regulation of the electricity industry - staff report on a Keystone policy dialogue

    SciTech Connect

    1996-05-01

    For over two years, The Keystone Center facilitated a dialogue on State and Federal Regulation of the Electricity Industry. The intent of this report is to assist policy-makers faced with decisions about changes to traditional utility regulation and planning and provide an overview of a diverse group`s deliberations on regulatory jurisdictional conflicts. This report is not a consensus document, rather it is a staff written summary of two years of discussion on the issues. The participants in the Keystone Dialogue believed that all affected interests could benefit from, if nothing else, a summary of their discussions of state/federal issues. The electric utility industry is one of the last remaining, heavily regulated industries in the United States. Rate and corporate regulation is split between state and federal governments and there is distinct regulatory authority at each level. For example, retail rate regulation occurs at the state level, the Federal Energy Regulatory Commission is responsible for wholesale rate regulation under the Federal Power Act, and the Securities and Exchange Commission oversees registered utility holding companies as defined under the Public Utility Holding Company Act of 1935. This jurisdictional split between state and federal regulation has evolved over many years through legislation and litigation on such matters. The creation of this allocation of regulatory responsibility was initiated in 1935 with the passage of the Public Utility Holding Company Act and the Federal Power Act when the economic and technological changes that are now occurring in the industry simply could not have been envisioned.

  13. Human Endometrial DNA Methylome Is Cycle-Dependent and Is Associated With Gene Expression Regulation

    PubMed Central

    Houshdaran, Sahar; Zelenko, Zara; Irwin, Juan C.

    2014-01-01

    Human endometrium undergoes major gene expression changes, resulting in altered cellular functions in response to cyclic variations in circulating estradiol and progesterone, largely mediated by transcription factors and nuclear receptors. In addition to classic modulators, epigenetic mechanisms regulate gene expression during development in response to environmental factors and in some diseases and have roles in steroid hormone action. Herein, we tested the hypothesis that DNA methylation plays a role in gene expression regulation in human endometrium in different hormonal milieux. High throughput, genome-wide DNA methylation profiling of endometrial samples in proliferative, early secretory, and midsecretory phases revealed dynamic DNA methylation patterns with segregation of proliferative from secretory phase samples by unsupervised cluster analysis of differentially methylated genes. Changes involved different frequencies of gain and loss of methylation within or outside CpG islands. Comparison of changes in transcriptomes and corresponding DNA methylomes from the same samples revealed association of DNA methylation and gene expression in a number of loci, some important in endometrial biology. Human endometrial stromal fibroblasts treated in vitro with estradiol and progesterone exhibited DNA methylation changes in several genes observed in proliferative and secretory phase tissues, respectively. Taken together, the data support the observation that epigenetic mechanisms are involved in gene expression regulation in human endometrium in different hormonal milieux, adding endometrium to a small number of normal adult tissues exhibiting dynamic DNA methylation. The data also raise the possibility that the interplay between steroid hormone and methylome dynamics regulates normal endometrial functions and, if abnormal, may result in endometrial dysfunction and associated disorders. PMID:24877562

  14. MFGE8 regulates TGF-β-induced epithelial mesenchymal transition in endometrial epithelial cells in vitro.

    PubMed

    Yu, Liang; Hu, Rong; Sullivan, Claretta; Swanson, R James; Oehninger, Sergio; Sun, Ying-Pu; Bocca, Silvina

    2016-09-01

    This study investigated the role of milk fat globule-epidermal growth factor-factor 8 (MFGE8) in TGF-β-induced epithelial-mesenchymal transition (EMT) of endometrial epithelial cells. These were in vitro studies using human endometrial epithelial cells and mouse blastocysts. We investigated the ability of TGF-β to induce EMT in endometrial epithelial cells (HEC-1A) by assessment of cytological phenotype (by light and atomic force microscopy), changes in expression of the markers of cell adhesion/differentiation E- and N-cadherin, and of the transcription factor Snail (by immunofluorescence and immunoblotting), and competence to support embryo attachment in a mouse blastocyst outgrowth assay. We also studied the effects of E-cadherin expression in cells transfected by retroviral shRNA vectors specifically silencing MFGE8. Results demonstrated that TGF-β induced EMT as demonstrated by phenotypic cell changes, by a switch of cadherin expression as well as by upregulation of the expression of the mesenchymal markers Snail and Vimentin. Upon MFGE8 knockdown, these processes were interfered with, suggesting that MFGE8 and TGF-β together may participate in regulation of EMT. This study demonstrated for the first time that endometrial MFGE8 modulates TGF-β-induced EMT in human endometrium cells. PMID:27340235

  15. The Regulation of Vascular Endothelial Growth Factor by Hypoxia and Prostaglandin F2α during Human Endometrial Repair

    PubMed Central

    Maybin, Jacqueline A.; Hirani, Nikhil; Brown, Pamela; Jabbour, Henry N.

    2011-01-01

    Context: The human endometrium has an exceptional capacity for repeated repair after menses, but its regulation remains undefined. Premenstrually, progesterone levels fall and prostaglandin (PG) F2α synthesis increases, causing spiral arteriole constriction. We hypothesized that progesterone withdrawal, PGF2α, and hypoxia increase vascular endothelial growth factor (VEGF), an endometrial repair factor. Design and Results: Endometrial biopsies were collected (n = 47) with ethical approval and consent. VEGF mRNA, quantified by quantitative RT-PCR, was increased during menstruation (P < 0.01).VEGF protein was maximally secreted from proliferative endometrial explants. Treatment of an endometrial epithelial cell line and primary human endometrial stromal cells with 100 nm PGF2α or hypoxia (0.5% O2) resulted in significant increases in VEGF mRNA and protein. VEGF was maximal when cells were cotreated with PGF2α and hypoxia simultaneously (P < 0.05–0.001). Secretory-phase endometrial explants also showed an increase in VEGF with cotreatment (P < 0.05). However, proliferative-phase explants showed no increase in VEGF on treatment with PGF2α and/or hypoxia. Proliferative tissue was induced to increase VEGF mRNA expression when exposed to progesterone and its withdrawal in vitro but only in the presence of hypoxia and PG. Hypoxia-inducible factor-1α (HIF-1α) silencing with RNA interference suppressed hypoxia-induced VEGF expression in endometrial cells but did not alter PGF2α-induced VEGF expression. Conclusions: Endometrial VEGF is increased at the time of endometrial repair. Progesterone withdrawal, PGF2α, and hypoxia are necessary for this perimenstrual VEGF expression. Hypoxia acts via HIF-1α to increase VEGF, whereas PGF2α acts in a HIF-1α-independent manner. Hence, two pathways regulate the expression of VEGF during endometrial repair. PMID:21677035

  16. Novel Roles for Hypoxia and Prostaglandin E2 in the Regulation of IL-8 During Endometrial Repair

    PubMed Central

    Maybin, Jacqueline A.; Hirani, Nikhil; Jabbour, Henry N.; Critchley, Hilary O.D.

    2011-01-01

    The endometrium has a remarkable capacity for efficient repair; however, factors involved remain undefined. Premenstrual progesterone withdrawal leads to increased prostaglandin (PG) production and local hypoxia. Here we determined human endometrial expression of interleukin-8 (IL-8) and the roles of PGE2 and hypoxia in its regulation. Endometrial biopsy specimens (n = 51) were collected. Endometrial cells and explants were exposed to 100 nmol/L of PGE2 or 0.5% O2. The endometrial IL-8 concentration peaked during menstruation (P < 0.001) and had a significant proangiogenic effect. IL-8 was increased by PGE2 and hypoxia in secretory but not proliferative explants, which suggests that exposure to progesterone is essential. In vitro progesterone withdrawal induced significant IL-8 up-regulation in proliferative explants primed with progestins, but only in the presence of hypoxia. Epithelial cells treated simultaneously with PGE2 and hypoxia demonstrated synergistic increases in IL-8. Inhibition of HIF-1 by short hairpin RNA abolished hypoxic IL-8 induction, and inhibition of NF-κB by an adenoviral dominant negative inhibitor decreased PGE2-induced IL-8 expression (P > 0.05). Increased menstrual IL-8 is consistent with a role in repair. Progesterone withdrawal, hypoxia, and PGE2 regulate endometrial IL-8 by acting via HIF-1 and NF-κB. Hence, progesterone withdrawal may activate two distinct pathways to initiate endometrial repair. PMID:21356375

  17. Endometrial ablation

    MedlinePlus

    Hysteroscopy-endometrial ablation; Laser thermal ablation; Endometrial ablation-radiofrequency; Endometrial ablation-thermal balloon ablation; Rollerball ablation; Hydrothermal ablation; Novasure ablation

  18. The influence of the WWOX gene on the regulation of biological processes during endometrial carcinogenesis.

    PubMed

    Płuciennik, E; Nowakowska, M; Gałdyszyńska, M; Popęda, M; Bednarek, A K

    2016-03-01

    The purpose of the present study was to investigate the role of WW domain containing oxidoreductase (WWOX) downregulation in biological cancer-related processes in normal (non-malignant) and cancer endometrial cell lines. We created an in vitro model using the normal endometrial cell line, THESC, and 2 endometrial cancer cell lines with varying degrees of differentiation, the Ishikawa (well-differentiated) and the MFE296 (moderately differentiated) cells, in which the WWOX tumor suppressor gene was silenced using Gipz lentiviral shRNA. In this model, we examined the changes in invasiveness via biological assays, such as zymography, migration through a basement membrane, the adhesion of cells to extracellular matrix proteins, anchorage-independent growth and colony formation assay. We also evaluated the correlation between the mRNA expression of the WWOX gene and genes involved in the processes of carcinogenesis, namely catenin beta-1 (CTNNB1) and zinc finger E-box binding homeobox 1 (ZEB1) (gene transcription), cadherin 1 (CDH1) and ezrin (EZR) (cell adhesion), vimentin (VIM) (structural proteins), as well as phosphatase and tensin homolog (PTEN) (tumor suppression) and secreted protein, acidic, cysteine-rich (osteonectin) (SPARC) (SPARC) (cell growth regulation) by RT-qPCR. Downregulation of the WWOX gene in the moderately differentiated MFE296 cell line caused decreased migratory capacity, and a reduction of matrix metalloproteinase-2 (MMP-2) activity. However, these cells grew in semisolid medium and exhibited higher expression of CDH1 and EZR (cell adhesion) and secreted protein, acidic, cysteine-rich (osteonectin) (SPARC) (cell growth regulation). Moreover, in the well-differentiated endometrial cancer (Ishikawa) cell line, WWOX gene silencing resulted in an increased ability of the cells to proliferate indefinitely. Additionally, WWOX regulated changes in adhesion potential in both the normal and cancer cell lines. Our results suggest that the

  19. Progesterone-regulated changes in endometrial gene expression contribute to advanced conceptus development in cattle.

    PubMed

    Forde, N; Carter, F; Fair, T; Crowe, M A; Evans, A C O; Spencer, T E; Bazer, F W; McBride, R; Boland, M P; O'Gaora, P; Lonergan, P; Roche, J F

    2009-10-01

    The postovulatory rise in circulating progesterone (P4) concentrations is associated with increased pregnancy success in beef and dairy cattle. Our study objective was to determine how elevated P4 alters endometrial gene expression to advance conceptus development. Synchronized heifers were inseminated (Day 0) and randomly assigned to pregnant high P4 or to pregnant normal P4. All high P4 groups received a P4-release intravaginal device on Day 3 after insemination that increased P4 concentrations up to Day 7 (P < 0.05). Tissue was collected on Day 5, 7, 13, or 16 of pregnancy, and endometrial gene expression was analyzed using the bovine Affymetrix (Santa Clara, CA) microarrays. Microarray analyses demonstrated that the largest number of P4-regulated genes coincided with the day when the P4 profiles were different for the longest period. Genes with the largest fold change increase (such as DGAT2 and MSTN [also known as GDF8]) were associated with triglyceride synthesis and glucose transport, which can be utilized as an energy source for the developing embryo. Temporal changes occurred at different stages of early pregnancy, with the greatest difference occurring between well-separated stages of conceptus development. Validation of a number of genes by quantitative real-time PCR indicated that P4 supplementation advances endometrial gene expression by altering the time (FABP, DGAT2, and MSTN) or duration (CRYGS) of expression pattern for genes that contribute to the composition of histotroph. PMID:19553605

  20. Endometrial cancer-associated mutants of SPOP are defective in regulating estrogen receptor-α protein turnover.

    PubMed

    Zhang, P; Gao, K; Jin, X; Ma, J; Peng, J; Wumaier, R; Tang, Y; Zhang, Y; An, J; Yan, Q; Dong, Y; Huang, H; Yu, L; Wang, C

    2015-01-01

    Increasing amounts of evidence strongly suggests that dysregulation of ubiquitin-proteasome system is closely associated with cancer pathogenesis. Speckle-type POZ protein (SPOP) is an adapter protein of the CUL3-based E3 ubiquitin ligase complexes. It selectively recruits substrates for their ubiquitination and subsequent degradation. Recently, several exome-sequencing studies of endometrial cancer revealed high frequency somatic mutations in SPOP (5.7-10%). However, how SPOP mutations contribute to endometrial cancer remains unknown. Here, we identified estrogen receptor-α (ERα), a major endometrial cancer promoter, as a substrate for the SPOP-CUL3-RBX1 E3 ubiquitin ligase complex. SPOP specifically recognizes multiple Ser/Thr (S/T)-rich degrons located in the AF2 domain of ERα, and triggers ERα degradation via the ubiquitin-proteasome pathway. SPOP depletion by siRNAs promotes endometrial cells growth. Strikingly, endometrial cancer-associated mutants of SPOP are defective in regulating ERα degradation and ubiquitination. Furthermore, we found that SPOP participates in estrogen-induced ERα degradation and transactivation. Our study revealed novel molecular mechanisms underlying the regulation of ERα protein homeostasis in physiological and pathological conditions, and provided insights in understanding the relationship between SPOP mutations and the development of endometrial cancer. PMID:25766326

  1. Estradiol regulates MICA expression in human endometrial cells

    PubMed Central

    Basu, Satarupa; Pioli, Patricia A.; Conejo-Garcia, Jose; Wira, Charles R.; Sentman, Charles L.

    2008-01-01

    The human endometrium undergoes cyclical changes regulated by sex hormones. Evidence suggests sex hormones regulate NK cell recruitment into the uterus in large numbers. NKG2D is an activating receptor expressed on human NK cells, γδ and CD8 T cells. NKG2D ligands are known to be sensors of cellular “stress”. In this study, we investigated whether sex hormones directly regulate expression of NKG2D ligands in the human uterus. Estradiol increased MICA expression on uterine epithelial cells; regulation was estrogen receptor-dependent. Real-time PCR analysis showed that NKG2D ligands MICA and MICB were expressed in the human endometrium. MICA protein was detected primarily on epithelial cells, and greater expression was observed in immunohistochemical analysis of tissues from patients in the secretory phase of the menstrual cycle. Thus, estrogens regulate expression of MICA. These data suggest hormonal regulation of innate immunity and NKG2D-mediated recognition in other tissues and diseases where estrogen may be involved. PMID:18728002

  2. Polychlorinated biphenyls impair endometrial receptivity in vitro via regulating mir-30d expression and epithelial mesenchymal transition.

    PubMed

    Cai, Jia-Li; Liu, Lan-Lan; Hu, Yuqin; Jiang, Xiao-Ming; Qiu, Hui-Ling; Sha, Ai-Guo; Wang, Chong-Gang; Zuo, Zheng-Hong; Ren, Jian-Zhi

    2016-07-15

    Polychlorinated biphenyls (PCBs) are ubiquitous legacy persistent pollutants and epidemiological data showed that PCB burdens were associated with failed implantation in human. However, the mechanism how PCB exposure affects the embryo implantation is not clear. Using an in vitro model for human embryo implantation employing the human choriocarcinoma cell line JAR and the human endometrial cell line Ishikawa, we have shown that PCB mixture Aroclor 1254 at environmental-relevant concentrations (2.5, 12.5, and 62.5μM) dose-dependently impaired the endometrial receptivity by reducing the adhesion of JAR spheroid attachment and increasing the spheroid outgrowth. The receptive-up-regulated micro-RNA, mir-30d was also down-regulated in endometrial cells by the exposure. Following transient transfection of mir-30d mimic, the disrupted attachment and outgrowth of JAR spheroids was partially restored in the model. By measurement of cadherin switch and vimentin expression, the PCB exposure also activated epithelial mesenchymal transition (EMT) in endometrial cells. In accordance, mir-30d mimic suppressed the EMT markers induced by PCBs. Luciferase reporter assay confirmed that the EMT regulator Snai1 was targeted by mir-30d, and the expression of Snai1 was dose-dependently up-regulated by PCB exposure. Taken together, our study revealed that PCBs may affect the receptivity of endometrial cells by impairing the interaction between receptivity-up-regulated microRNA and EMT process. PMID:27481218

  3. Progesterone regulation of the endometrial WNT system in the ovine uterus.

    PubMed

    Satterfield, M Carey; Song, Gwonhwa; Hayashi, Kanako; Bazer, Fuller W; Spencer, Thomas E

    2008-01-01

    WNT signalling regulates cell proliferation, differentiation, polarity and organisation. The present study investigated the effects of progesterone (P4) on the endometrial WNT system in relation to blastocyst development and growth in sheep. Ewes received daily intramuscular injections of either corn oil (CO) vehicle or 25 mg P4 from 36 h after mating (Day 0) until hysterectomy on Day 9 or 12. Another group received P4 until Day 8 and 75 mg mifepristone (RU486) from Day 8 to Day 12. Early P4 treatment increased blastocyst growth on Days 9 and 12, whereas no blastocysts were recovered from P4 + RU486-treated ewes. Levels of WNT2 mRNA in the stroma and WNT11 and WNT7A mRNAs in the endometrial luminal epithelia (LE) were reduced in P4 + RU486-treated ewes on Day 9, whereas WNT11 mRNA was reduced in the endometria of both P4- and P4 + RU486-treated ewes on Day 12. On Day 12, WNT2 mRNA was increased in the stroma, WNT7A mRNA was increased in the LE and WNT5A mRNA was increased in the LE and stroma of P4 + RU486- compared with P4-treated ewes. DKK1 mRNA was absent in the endometrial stroma of P4 + RU486-treated ewes. Expression of transcription factor 7 like-2 (TCF7L2) was transiently increased in endometrial epithelia of P4-treated ewes on Day 9, but decreased in these ewes on Day 12. MSX1 mRNA was decreased by P4 treatment on Day 9 and levels of both MSX1 and MSX2 mRNA were higher in P4 + RU486-treated ewes on Day 12. Thus, P4 modulates the endometrial WNT system and elicits a transient decline in selected WNT pathways and signalling components, which is hypothesised to alter tight and adherens junctions, thereby stimulating blastocyst growth and development. PMID:19007558

  4. MicroRNA-212 Regulates the Expression of Olfactomedin 1 and C-Terminal Binding Protein 1 in Human Endometrial Epithelial Cells to Enhance Spheroid Attachment In Vitro.

    PubMed

    Kottawatta, Kottawattage S A; So, Kam-Hei; Kodithuwakku, Suranga P; Ng, Ernest H Y; Yeung, William S B; Lee, Kai-Fai

    2015-11-01

    Successful embryo implantation requires a synchronized dialogue between a competent blastocyst and the receptive endometrium, which occurs in a limited time period known as the "window of implantation." Recent studies suggested that down-regulation of olfactomedin 1 (OLFM1) in the endometrium and fallopian tube is associated with receptive endometrium and tubal ectopic pregnancy in humans. Interestingly, the human chorionic gonadotropin (hCG) induces miR-212 expression, which modulates OLFM1 and C-terminal binding protein 1 (CTBP1) expressions in mouse granulosa cells. Therefore, we hypothesized that embryo-derived hCG would increase miR-212 expression and down-regulate OLFM1 and CTBP1 expressions to favor embryo attachment onto the female reproductive tract. We found that hCG stimulated the expression of miR-212 and down-regulated OLFM1 but not CTBP1 mRNA in both human endometrial (Ishikawa) and fallopian (OE-E6/E7) epithelial cells. However, hCG suppressed the expression of OLFM1 and CTBP1 proteins in both cell lines. The 3'UTR of both OLFM1 and CTBP1 contained binding sites for miR-212. The miR-212 precursor suppressed luciferase expression, whereas the miR-212 inhibitor stimulated luciferase expression of the wild-type (WT)-OLFM1 and WT-CTBP1 reporter constructs. Furthermore, hCG (25 IU/ml) treatments stimulated trophoblastic (Jeg-3) spheroid (blastocyst surrogate) attachment onto Ishikawa and OE-E6/E7 cells. Transfection of miR-212 precursor increased Jeg-3 spheroid attachment onto Ishikawa cells and decreased OLFM1 and CTBP1 protein expressions, whereas the opposite occurred with miR-212 inhibitor. Taken together, hCG stimulated miR-212, which in turn down-regulated OLFM1 and CTBP1 expression in fallopian and endometrial epithelial cells to favor spheroid attachment. PMID:26377223

  5. The orphan nuclear receptor Nur77 regulates decidual prolactin expression in human endometrial stromal cells

    SciTech Connect

    Jiang, Yue; Hu, Yali; Zhao, Jing; Zhen, Xin; Yan, Guijun; Sun, Haixiang

    2011-01-14

    Research highlights: {yields} Decidually produced PRL plays a key role during pregnancy. {yields} Overexpression of Nur77 increased PRL mRNA expression and enhanced decidual PRL promoter activity. {yields} Knockdown of Nur77 decreased decidual PRL secretion induced by 8-Br-cAMP and MPA. {yields} Nur77 is a novel transcription factor that plays an active role in decidual prolactin expression. -- Abstract: Prolactin (PRL) is synthesized and released by several extrapituitary tissues, including decidualized stromal cells. Despite the important role of decidual PRL during pregnancy, little is understood about the factors involved in the proper regulation of decidual PRL expression. Here we present evidence that the transcription factor Nur77 plays an active role in decidual prolactin expression in human endometrial stromal cells (hESCs). Nur77 mRNA expression in hESCs was significantly increased after decidualization stimulated by 8-Br-cAMP and medroxyprogesterone acetate (MPA). Adenovirus-mediated overexpression of Nur77 in hESCs markedly increased PRL mRNA expression and enhanced decidual PRL promoter (dPRL/-332Luc) activity in a concentration-dependent manner. Furthermore, knockdown of Nur77 in hESCs significantly decreased decidual PRL promoter activation and substantially attenuated PRL mRNA expression and PRL secretion (P < 0.01) induced by 8-Br-cAMP and MPA. These results demonstrate that Nur77 is a novel transcription factor that contributes significantly to the regulation of prolactin gene expression in human endometrial stromal cells.

  6. Identification and Characterization of Progesterone- and Estrogen-Regulated MicroRNAs in Mouse Endometrial Epithelial Cells

    PubMed Central

    Yuan, Dong-zhi; Yu, Lin-lin; Qu, Ting; Zhang, Shi-mao; Zhao, You-bo; Pan, Jun-li; Xu, Qian; He, Ya-ping; Zhang, Jin-hu

    2015-01-01

    In endometrial epithelial cells, progesterone (P4) functions in regulating the cell structure and opposing the effects of estrogen. However, the mechanisms of P4 that oppose the effects of estrogen remain unclear. MicroRNAs (miRNAs) are important posttranscriptional regulators that are involved in various physiological and pathological processes. Whether P4 directly induces miRNA expression to antagonize estrogen in endometrial epithelium is unclear. In this study, total RNAs were extracted from endometrial epithelium of ovariectomized mice, which were treated with estrogen alone or a combination of estrogen and P4. MicroRNA high-throughput sequencing with bioinformatics analysis was used to identify P4-induced miRNAs, predict their potential target genes, and analyze their possible biological functions. We observed that 146 mature miRNAs in endometrial epithelial cells were significantly upregulated by P4. These miRNAs were extensively involved in multiple biological processes. The miRNA-145a demonstrated a possible function in the antiproliferative action of P4 on endometrial epithelial cells. PMID:24925854

  7. Microarray Analysis on Gene Regulation by Estrogen, Progesterone and Tamoxifen in Human Endometrial Stromal Cells

    PubMed Central

    Ren, Chun-E; Zhu, Xueqiong; Li, Jinping; Lyle, Christian; Dowdy, Sean; Podratz, Karl C.; Byck, David; Chen, Hai-Bin; Jiang, Shi-Wen

    2015-01-01

    Epithelial stromal cells represent a major cellular component of human uterine endometrium that is subject to tight hormonal regulation. Through cell-cell contacts and/or paracrine mechanisms, stromal cells play a significant role in the malignant transformation of epithelial cells. We isolated stromal cells from normal human endometrium and investigated the morphological and transcriptional changes induced by estrogen, progesterone and tamoxifen. We demonstrated that stromal cells express appreciable levels of estrogen and progesterone receptors and undergo different morphological changes upon hormonal stimulation. Microarray analysis indicated that both estrogen and progesterone induced dramatic alterations in a variety of genes associated with cell structure, transcription, cell cycle, and signaling. However, divergent patterns of changes, and in some genes opposite effects, were observed for the two hormones. A large number of genes are identified as novel targets for hormonal regulation. These hormone-responsive genes may be involved in normal uterine function and the development of endometrial malignancies. PMID:25782154

  8. Endometrial CXCL13 Expression Is Cycle Regulated in Humans and Aberrantly Expressed in Humans and Rhesus Macaques With Endometriosis

    PubMed Central

    Franasiak, Jason M.; Burns, Katherine A.; Slayden, Ov; Yuan, Lingwen; Fritz, Marc A.; Korach, Kenneth S.; Lessey, Bruce A.

    2014-01-01

    C-X-C ligand 13 (CXCL13), a regulator of mucosal immunity, is secreted by human endometrial epithelium and may be involved in embryo implantation. However, cyclic expression of human endometrial CXCL13 in health and disease is not well studied. This study examines cycle stage-specific endometrial CXCL13 expression in normal humans when compared to those with biopsy-confirmed, stage 1 to 4 endometriosis using real-time reverse transcriptase, real-time polymerase chain reaction and immunohistochemistry. Eutopic endometrial CXCL13 expression was also compared between normal, control Rhesus macaques, and macaques with advanced endometriosis. In healthy women, CXLC13 messenger RNA expression was minimal in the proliferative phase and maximal in the secretory phase. However, in the presence of endometriosis, proliferative-phase endometrial expression markedly increased in both humans and rhesus subjects (P < .05). The cross-species and cross-stage concordance suggests a pathophysiologic role for CXCL13 in endometriosis and its use as a biomarker for disease. PMID:25031316

  9. Rapid estrogen signaling negatively regulates PTEN activity through phosphorylation in endometrial cancer cells

    PubMed Central

    Scully, Melanie M.; Palacios-Helgeson, Leslie K.; Wah, Lah S.; Jackson, Twila A.

    2014-01-01

    Hyperestrogenicity is a risk factor for endometrial cancer. 17β-estradiol (E2) is known to stimulate both genomic and nongenomic estrogen receptor-α (ERα) actions in a number of reproductive tissues. However, the contributions of transcription-independent ERα signaling on normal and malignant endometrium are not fully understood. Phosphatase and tensin homolog (PTEN) is a tumor suppressor that decreases cellular mitosis primarily through negative regulation of the phosphoinositide 3-kinase/AKT signaling axis. PTEN levels are elevated during the E2 dominated, mitotically active, proliferative phase of the menstrual cycle, indicating possible hormonal regulation of PTEN in the uterus. In order to determine if rapid E2 signaling regulates PTEN, we used ERα positive, PTEN positive, endometrial cells. We show that cytosolic E2/ERα signaling leads to increased phosphorylation of PTEN at key regulatory residues. Importantly, E2 stimulation decreased PTEN lipid phosphatase activity and caused consequent increases in phospho-AKT. We further demonstrate that cytosolic ERα forms a complex with PTEN in an E2-dependent manner, and that ERα constitutively complexes with protein kinase2-α (CK2α), a kinase previously shown to phosphorylate the C-terminal tail of PTEN. These results provide mechanistic support for an E2-dependent, ERα cytosolic signaling complex that negatively regulates PTEN activity through carboxy terminus phosphorylation. Using an animal model, we show that sustained E2 signaling results in increased phospho-PTEN (S380, T382, T383), total PTEN and phospho-AKT (S473). Taken together, we provide a novel mechanism in which transcription-independent E2/ERα signaling may promote a pro-tumorigenic environment in the endometrium. PMID:24844349

  10. The Kruppel-like factor 9 (KLF9) network in HEC-1-A endometrial carcinoma cells suggests the carcinogenic potential of dys-regulated KLF9 expression

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Krüppel-like factor 9 (KLF9) is a transcriptional regulator of uterine endometrial cell proliferation, adhesion and differentiation; processes essential for pregnancy success and which are subverted during tumorigenesis. The network of endometrial genes controlled by KLF9 is largely unknown. Over-...

  11. Endometrial cancer

    MedlinePlus

    ... Endometrial biopsy Dilation and curettage ( D and C ) Pap smear (may raise a suspicion for endometrial cancer, but ... for more than 2 years. Frequent pelvic exams, Pap smears and endometrial biopsy may be considered in some ...

  12. Macrophages regulate expression of α1,2-fucosyltransferase genes in human endometrial epithelial cells.

    PubMed

    Nakamura, Hitomi; Jasper, Melinda J; Hull, M Louise; Aplin, John D; Robertson, Sarah A

    2012-04-01

    The epithelial cell surface of the endometrium undergoes substantial biochemical changes to allow embryo attachment and implantation in early pregnancy. We hypothesized that tissue macrophages influence these events to promote uterine receptivity. To investigate the role of macrophages in regulating epithelial cell expression of genes linked to glycan-mediated embryo adhesion, Ishikawa, RL95-2 and HEC1A endometrial epithelial cells were cultured alone or with unactivated or lipopolysaccharide-activated monocytic U937 cells, separated using transwell inserts. Expression of mRNAs encoding two α1,2-fucosyltransferases (FUT1, FUT2) was increased in all three epithelial cell lines following co-culture with U937 cells, and was associated with increased fucosylation of cell surface glycoproteins detected using lectins from Ulex europaeus (UEA-1) and Dolichos biflorus (DBA). FUT1 induction by U937 cells also occurred in primary endometrial epithelial cells collected in luteal but not proliferative phase. Activation of the interleukin-6 (IL6)/leukemia inhibitory factor (LIF) cytokine signaling pathway with phosphorylation of STAT3 and elevated SOCS3 mRNA expression was evident in epithelial cells stimulated by U937 co-culture. Several recombinant macrophage-secreted cytokines exerted stimulatory or inhibitory effects on FUT1 and FUT2 mRNA expression, and the macrophage-derived cytokine LIF partially replicated the effects of U937 cells on both FUT1 and FUT2 expression and UEA-1 and DBA lectin reactivity in Ishikawa cells. These results suggest that macrophage-derived factors including LIF might facilitate development of an implantation-receptive endometrium by regulating surface glycan structures in epithelial cells. Abnormal phenotypes or altered abundance of uterine macrophages could contribute to the pathophysiology of primary unexplained infertility in women. PMID:22053055

  13. Mig-6 regulates endometrial genes involved in cell cycle and progesterone signaling

    SciTech Connect

    Yoo, Jung-Yoon; Kim, Tae Hoon; Lee, Jae Hee; Dunwoodie, Sally L.; Ku, Bon Jeong; Jeong, Jae-Wook

    2015-07-10

    Mitogen inducible gene 6 (Mig-6) is an important mediator of progesterone (P4) signaling to inhibit estrogen (E2) signaling in the uterus. Ablation of Mig-6 in the murine uterus leads to the development of endometrial hyperplasia and E2-induced endometrial cancer. To identify the molecular pathways regulated by Mig-6, we performed microarray analysis on the uterus of ovariectomized Mig-6{sup f/f} and PGR{sup cre/+}Mig-6{sup f/f} (Mig-6{sup d/d}) mice treated with vehicle or P4 for 6 h. The results revealed that 772 transcripts were significantly regulated in the Mig-6{sup d/d} uterus treated with vehicle as compared with Mig-6{sup f/f} mice. The pathway analysis showed that Mig-6 suppressed the expression of gene-related cell cycle regulation in the absence of ovarian steroid hormone. The epithelium of Mig-6{sup d/d} mice showed a significant increase in the number of proliferative cells compared to Mig-6{sup f/f} mice. This microarray analysis also revealed that 324 genes are regulated by P4 as well as Mig-6. Cited2, the developmentally important transcription factor, was identified as being regulated by the P4-Mig-6 axis. To determine the role of Cited2 in the uterus, we used the mice with Cited2 that were conditionally ablated in progesterone receptor-positive cells (PGR{sup cre/+}Cited2{sup f/f}; Cited2{sup d/d}). Ablation of Cited2 in the uterus resulted in a significant reduction in the ability of the uterus to undergo a hormonally induced decidual reaction. Identification and analysis of these responsive genes will help define the role of P4 as well as Mig-6 in regulating uterine biology. - Highlights: • We identify Mig-6- and P4-regulated uterine genes by microarray analysis. • Mig-6 suppresses cell cycle progression and epithelial cell proliferation in uterus. • We identify the Mig-6 dependent induced genes by P4. • Cited2 plays an important role for decidualization as a P4 and Mig-6 target gene.

  14. Uterine Natural Killer cells regulate endometrial bleeding in women and are suppressed by the progesterone receptor modulator asoprisnil

    PubMed Central

    Wilkens, Julia; Male, Victoria; Ghazal, Peter; Forster, Thorsten; Gibson, Douglas A.; Williams, Alistair RW; Brito-Mutunayagam, Savita L; Craigon, Marie; Lourenco, Paula; Cameron, Iain T; Chwalisz, Kristof; Moffett, Ashley; Critchley, Hilary OD

    2013-01-01

    Uterine NK cells (uNK) play a role in the regulation of placentation but their functions in non-pregnant endometrium are not understood. We have previously reported suppression of endometrial bleeding and alteration of spiral artery morphology in women exposed to asoprisnil, a progesterone receptor modulator. We now compare global endometrial gene expression in asoprisnil-treated versus control women, and we demonstrate a statistically significant reduction of genes in the IL-15 pathway, known to play a key role in uNK development and function. Suppression of IL-15 by asoprisnil was also observed at mRNA level (p<0.05), and immunostaining for NK cell marker CD56 revealed a striking reduction of uNK in asoprisnil-treated endometrium (p<0.001). IL-15 levels in normal endometrium are progesterone-responsive. Progesterone receptor (PR) positive stromal cells transcribe both IL-15 and IL-15RA. Thus, the response of stromal cells to progesterone will be to increase IL-15 trans-presentation to uNK, supporting their expansion and differentiation. In asoprisnil-treated endometrium, there is a marked down-regulation of stromal PR expression and virtual absence of uNK. These novel findings indicate that the IL-15 pathway provides a missing link in the complex interplay between endometrial stromal cells, uNK and spiral arteries affecting physiological and pathological endometrial bleeding. PMID:23913972

  15. Ovarian steroid regulation of endometrial phospholipase A2 isoforms in horses.

    PubMed

    Ababneh, M M; Troedsson, M H T

    2013-04-01

    Real-time PCR was used to investigate the role of progesterone (P4) and oestradiol (E2) in regulation of endometrial cytosolic, secretory and calcium-independent phospholipase A2 (PLA2G4A, PLA2G2A and PLA2G6, respectively) gene expression. Ovariectomized mares underwent 6 days of E2 pre-treatment followed by 14 days of P4 supplementation. At the start of P4 treatment (Day 1), mares were assigned in a 2 × 2 factorial design to receive either E2 or vehicle starting on Day 11 and endometrial biopsy collection on either Day 14 when P4 concentrations remained high (>4 ng/ml) or Day 16 when P4 concentrations had declined (0.5-2 ng/ml). Additional biopsies were collected from ovariectomized mares on Day 8, which served as control. Blood samples were collected for P4 determination. PLA2G4A expression was higher (p < 0.05) on Day 14 compared with Day 8. In contrast, PLA2G2A did not change significantly (p < 0.12). PLA2G4A and PLA2G2A gene expression increased (p < 0.05), as P4 concentration dropped, on Day 16. In contrast, PLA2G6 gene expression did not show differences between days. Treatment with oestradiol did not increase PLA2 isoforms expression when compared to treatment with the vehicle. PLA2G4A and PLA2G2A were positively correlated with each other and negatively correlated with P4 concentrations. In conclusion, P4 withdrawal upregulated PLA2G4A and PLA2G2A gene expression, and this was not affected by E2. PLA2G4A and PLA2G2A but not PLA2G6 gene expression may be involved in controlling prostaglandin F2 alpha synthesis and luteolysis. PMID:22882596

  16. Regulation of inflammatory and angiogenesis mediators in a functional model of decidualized endometrial stromal cells.

    PubMed

    Bourdiec, Amélie; Ahmad, Syed-Furquan; Lachhab, Asmaa; Akoum, Ali

    2016-01-01

    The mechanisms involving the expression of interleukin (IL) 1 family members in the process of preparing the endometrium to receive an embryo remain unclear. In this study, decidualization differentially skewed the balance of IL1 family receptor expression in a pattern that increases endometrial stromal cell receptivity to IL1, IL18 and IL33. Additionally, endometrial cells showed increased expression of homeobox HOXA10 and HOXA11 and LIFR, which are known to be involved in endometrial embryo receptivity. Further analyses of decidual endometrial cells revealed a significant increase in the release of potent proinflammatory, remodelling and angiogenic factors implicated in the embryo invasion process, such as VEGF (P = 0.0305), MMP9 (P = 0.0003), TIMP3 (P = 0.0001), RANTES (P = 0.0020), MCP1 (P = 0.0001) and MIF (P = 0.0068). No significant changes in endogenous IL1B secretion were observed. Decreased secretion of IL18 and decidualization increased secretion of IL33. These findings reveal a significant modulation of endometrial cell receptivity to IL1 family members during endometrial stromal cell decidualization, and suggest that the involvement of IL1 family members is important in physiological processes of endometrial receptivity, including adaptive immunology. This may be relevant to establishing a favourable uterine microenvironment for embryo implantation. PMID:26602943

  17. S100A4 promotes endometrial cancer progress through epithelial-mesenchymal transition regulation.

    PubMed

    Hua, Teng; Liu, Shuangge; Xin, Xiaoyan; Cai, Liqiong; Shi, Rui; Chi, Shuqi; Feng, Dilu; Wang, Hongbo

    2016-06-01

    Epithelial-mesenchymal transition (EMT) is a major cause of endometrial cancer (EC) to initiate invasion and metastasis. S100A4, a calcium-binding protein, is implicated in multistage of tumorigenesis and tumor progression. The correlation between S100A4 and EMT in EC is still unclear. This study was aimed to clarify the role of S100A4 in EC and the relationship between S100A4 expression and EMT markers. S100A4, E-cadherin, and vimentin were detected in tissues of EC patients (n=50) by immunohistochemistry. The impact of S100A4 on EC cell proliferation, migration and invasion was investigated via RNA interference, and the correlation between S100A4 and EMT markers were also explored. The results showed that S100A4 was significantly increased in epithelial cells of EC compared with the normal endometrium (P<0.05), also S100A4 level was positively related to age (P=0.021), histological grade (P<0.001), and lymph node metastasis (P<0.001). Additionally, silencing of S100A4 remarkably attenuated EC cell migration and invasion. Significant morphological change accompanied with the downregulation of EMT markers, E-cadherin and vimentin were also observed. Aberrant S100A4 expression may predict EC progression and play an important role in regulating EC cell invasion through EMT regulation. Hence, S100A4 is a promising therapeutic target. PMID:27109209

  18. Early embryonic and endometrial regulation of tumor necrosis factor and tumor necrosis factor receptor 2 in the cattle uterus.

    PubMed

    Correia-Álvarez, E; Gómez, E; Martín, D; Carrocera, S; Pérez, S; Peynot, N; Giraud-Delville, C; Caamaño, J N; Balseiro, A; Sandra, O; Duranthon, V; Muñoz, M

    2015-04-01

    Tumor necrosis factor (TNF) alpha likely mediates embryomaternal communication in mammals. In bovine, we have previously found that the uterine fluid of heifers that carried early embryos shows downregulation in the TNF and nuclear factor κB system. In this work, we assessed the expression of TNF and its receptor TNFR2 in the bovine endometrium and embryos during blastocyst development. Moreover, to explore the endometrial immune response to early embryos, we analyzed the number of CD45 leukocytes in the bovine endometrium. Day 8 endometrium and blastocyst recovered from animals after transfer of Day 5 embryos showed TNF and TNFR2 mRNA transcription and protein colocalization. The presence of embryos increased endometrial TNF and TNFR2 protein, whereas endometrial leukocytes decreased. Blastocysts exposed to the uterine tract had undetectable levels of TNF and lower levels of TNFR2 mRNA. These results suggest that the endometrium might lower the TNF concentration in the blastocyst by (1) regulating TNF secretion into the uterine fluid and (2) inducing decreased TNF and TNFR2 mRNA transcription in the embryo. Thus, TNF and TNFR2 might participate in early embryomaternal communication. PMID:25589228

  19. [Endometrial imaging].

    PubMed

    Lemercier, E; Genevois, A; Dacher, J N; Benozio, M; Descargues, G; Marpeau, L

    2000-12-01

    The diagnostic value of endovaginal sonography in benign or malignant endometrial pathology is high, increased by sonohysterography. Sonohysterography is useful in the diagnosis of endometrial thickness and to determine further investigations. MRI is accurate in the uterine adenomyosis diagnosis and is the imaging modality of choice for the preoperative endometrial cancer staging. PMID:11173754

  20. KRÜPPEL-LIKE FACTOR 9 AND REGULATION OF ENDOMETRIAL ESTROGEN RECEPTOR-ALPHA SIGNALING

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Endometrial cancer risk is linked to aberrant estrogen receptor-alpha (ER alpha) signaling caused by increased ER alpha activation due to hyper-estrogenic environments or mutations in growth-regulatory factors. We had shown that ER alpha signaling is attenuated by the Sp1-related transcription facto...

  1. mRNA-Binding Protein TIA-1 Reduces Cytokine Expression in Human Endometrial Stromal Cells and Is Down-Regulated in Ectopic Endometrium

    PubMed Central

    Karalok, Hakan Mete; Aydin, Ebru; Saglam, Ozlen; Torun, Aysenur; Guzeloglu-Kayisli, Ozlem; Lalioti, Maria D.; Kristiansson, Helena; Duke, Cindy M. P.; Choe, Gina; Flannery, Clare; Kallen, Caleb B.

    2014-01-01

    Background: Cytokines and growth factors play important roles in endometrial function and the pathogenesis of endometriosis. mRNAs encoding cytokines and growth factors undergo rapid turnover; primarily mediated by adenosine- and uridine-rich elements (AREs) located in their 3′-untranslated regions. T-cell intracellular antigen (TIA-1), an mRNA-binding protein, binds to AREs in target transcripts, leading to decreased gene expression. Objective: The purpose of this article was to determine whether TIA-1 plays a role in the regulation of endometrial cytokine and growth factor expression during the normal menstrual cycle and whether TIA-1 expression is altered in women with endometriosis. Methods: Eutopic endometrial tissue obtained from women without endometriosis (n = 30) and eutopic and ectopic endometrial tissues from women with endometriosis (n = 17) were immunostained for TIA-1. Staining intensities were evaluated by histological scores (HSCOREs). The regulation of endometrial TIA-1 expression by immune factors and steroid hormones was studied by treating primary cultured human endometrial stromal cells (HESCs) with vehicle, lipopolysaccharide, TNF-α, IL-6, estradiol, or progesterone, followed by protein blot analyses. HESCs were engineered to over- or underexpress TIA-1 to test whether TIA-1 regulates IL-6 or TNF-α expression in these cells. Results: We found that TIA-1 is expressed in endometrial stromal and glandular cells throughout the menstrual cycle and that this expression is significantly higher in the perimenstrual phase. In women with endometriosis, TIA-1 expression in eutopic and ectopic endometrium was reduced compared with TIA-1 expression in eutopic endometrium of unaffected control women. Lipopolysaccharide and TNF-α increased TIA-1 expression in HESCs in vitro, whereas IL-6 or steroid hormones had no effect. In HESCs, down-regulation of TIA-1 resulted in elevated IL-6 and TNF-α expression, whereas TIA-1 overexpression resulted in

  2. Hormones and endometrial carcinogenesis.

    PubMed

    Kamal, Areege; Tempest, Nicola; Parkes, Christina; Alnafakh, Rafah; Makrydima, Sofia; Adishesh, Meera; Hapangama, Dharani K

    2016-02-01

    Endometrial cancer (EC) is the commonest gynaecological cancer in the Western World with an alarmingly increasing incidence related to longevity and obesity. Ovarian hormones regulate normal human endometrial cell proliferation, regeneration and function therefore are implicated in endometrial carcinogenesis directly or via influencing other hormones and metabolic pathways. Although the role of unopposed oestrogen in the pathogenesis of EC has received considerable attention, the emerging role of other hormones in this process, such as androgens and gonadotropin-releasing hormones (GnRH) is less well recognised. This review aims to consolidate the current knowledge of the involvement of the three main endogenous ovarian hormones (oestrogens, progesterone and androgens) as well as the other hormones in endometrial carcinogenesis, to identify important avenues for future research. PMID:26966933

  3. SERPINA3 promotes endometrial cancer cells growth by regulating G2/M cell cycle checkpoint and apoptosis

    PubMed Central

    Yang, Guang-Dong; Yang, Xiao-Mei; Lu, Huan; Ren, Yuan; Ma, Ming-Ze; Zhu, Lin-Yan; Wang, Jing-Hao; Song, Wei-Wei; Zhang, Wen-Ming; Zhang, Rong; Zhang, Zhi-Gang

    2014-01-01

    Endometrial carcinoma (EC) is the most common gynecologic cancer worldwide and is one of the leading causes of death in women. Therefore, it is urgent to elucidate the pathological mechanisms of EC. SERPINA3 is a member of the serpin super-family of protease inhibitors. Its aberrant expression has been observed in various tumor cells. However, its clinical significance and biological function in endometrial cancer remains unknown. In the present study, we demonstrated that SERPINA3 expression was significantly up-regulated in EC samples and was closely correlated with lower differentiation, higher stage, positive lymph node or vascular thrombosis and negative estrogen receptor (ER), indicating a poor prognosis. We then demonstrated that SERPINA3 promoted EC cells proliferation by regulating G2/M checkpoint in cell cycle and inhibited cells apoptosis, and we further uncovered that the pro-proliferative effect of SERPINA3 on EC was likely ascribed to the activation of MAPK/ERK1/2 and PI3K/AKT signaling. The results of our study may provide insight into the application of SERPINA3 as a novel predictor of clinical outcomes and a potential therapeutic target of EC. PMID:24817931

  4. Estrogen Regulates the Tumour Suppressor MiRNA-30c and Its Target Gene, MTA-1, in Endometrial Cancer

    PubMed Central

    Yan, Yuhua; Guo, Feifei; Li, Jian; Hu, Yali; Zhou, Huaijun; Xun, Qingying

    2014-01-01

    MicroRNA-30c (miR-30c) has been reported to be a tumour suppressor in endometrial cancer (EC). We demonstrate that miR-30c is down-regulated in EC tissue and is highly expressed in estrogen receptor (ER)-negative HEC-1-B cells. MiR-30c directly inhibits MTA-1 expression and functions as a tumour suppressor via the miR-30c-MTA-1 signalling pathway. Furthermore, miR-30c is decreased upon E2 treatment in both ER-positive Ishikawa and ER-negative HEC-1-B cells. Taken together, our results suggest that miR-30c is an important deregulated miRNA in EC and might serve as a potential biomarker and novel therapeutic target for EC. PMID:24595016

  5. Lack of cyclical fluctuations of endometrial GLUT4 expression in women with polycystic ovary syndrome: Evidence for direct regulation of GLUT4 by steroid hormones

    PubMed Central

    Cui, Peng; Li, Xin; Wang, Xiaoqin; Feng, Yi; Lin, Jin-Fang; Billig, Håkan; Shao, Ruijin

    2015-01-01

    Background Determination of the role of steroid hormones in expression and regulation of endometrial glucose transport 4 (GLUT4) in humans is important for understanding endometrial disorders such as polycystic ovary syndrome (PCOS), a common hormone-imbalance disease. Methods Endometrial biopsy samples were collected from non-PCOS patients with regular menstrual cycles or with hyperplasia and from PCOS patients with or without hyperplasia. In addition, endometrial tissues from postmenopausal women were incubated with human chorionic gonadotropin (hCG, 10 IU/ml), 17β-estradiol (E2, 10 nM), progesterone (P4, 100 nM), or a combination of E2 and P4 for 24 h. The expression of GLUT4 was measured at the mRNA level using quantitative real-time polymerase chain reaction (qRT-PCR) and at the protein level using Western blot analysis and immunohistochemistry. Results A cyclical change in GLUT4 expression pattern was observed in non-PCOS patients, and a high level of GLUT4 expression was seen in the proliferative phase compared to the secretory phase. Low levels of GLUT4 expression were found in PCOS patients compared to menstrual cycle phase-matched non-PCOS patients, and there was no significant change in GLUT4 expression in PCOS patients during the menstrual cycle. GLUT4 was localized in both epithelial and stromal cells, with notable changes in epithelial cells. We postulate that decreased GLUT4 expression might be regulated by steroid hormones. In support of this, we showed that in cultured endometrial tissues hCG and E2 alone had no effect on GLUT4 expression. However, P4 alone and P4 in combination with E2 decreased GLUT4 expression. Compared with non-PCOS controls, PCOS patients with endometrial hyperplasia exhibited decreased GLUT4 expression in particular in the epithelial cells. Conclusion We conclude that P4 can induce changes in endometrial GLUT4 expression during the menstrual cycle and that abnormal hormonal conditions such as PCOS disrupt normal patterns

  6. Glucose-regulated protein 94 deficiency induces squamous cell metaplasia and suppresses PTEN-null driven endometrial epithelial tumor development

    PubMed Central

    Shen, Jieli; Yao, Lijing; Lin, Yvonne G.; DeMayo, Francesco J.; Lydon, John P.; Dubeau, Louis; Lee, Amy S.

    2016-01-01

    Endometrial carcinoma is the most prevalent gynecologic cancer in the United States. The tumor suppressor gene Pten (phosphatase and tensin homolog) is commonly mutated in the more common type 1 (endometrioid) subtype. The glucose-regulated protein 94 (GRP94) is emerging as a novel regulator for cancer development. Here we report that expression profiles from the Cancer Genome Atlas (TCGA) showed significantly increased Grp94 mRNA levels in endometrial tumor versus normal tissues, correlating with highly elevated GRP94 protein expression in patient samples and the requirement of GRP94 for maintaining viability of human endometrioid adenocarcinoma (EAC) cell lines. Through generation of uterus-specific knockout mouse models with deletion of Grp94 alone (c94f/f) or in combination with Pten (cPf/f94f/f), we discovered that c94f/f uteri induced squamous cell metaplasia (SCM) and reduced active nuclear β-catenin. The cPf/f94f/f uteri showed accelerated SCM and suppression of PTEN-null driven EAC, with reduced cellular proliferation, attenuated β-catenin signaling and decreased AKT/S6 activation in the SCM. In contrast to single PTEN knockout uteri (cPf/f), cPf/f94f/f uteri showed no decrease in E-cadherin level and no invasive lesion. Collectively, our study implies that GRP94 downregulation induces SCM in EAC and suppresses AKT/S6 signaling, providing a novel mechanism for suppressing EAC progression. PMID:26910913

  7. CAPN 7 promotes the migration and invasion of human endometrial stromal cell by regulating matrix metalloproteinase 2 activity

    PubMed Central

    2013-01-01

    Background Matrix metalloproteinase 2 (MMP-2) has been reported to be an important regulator of cell migration and invasion through degradation of the extracellular matrix (ECM) in many diseases, such as cancer and endometriosis. Here, we found calcium-activated neutral protease 7 (CAPN 7) expression was markedly upregulated in the eutopic endometrium and endometrial stromal cells of women diagnosed with endometriosis. Our studies were carried out to detect the effects of CAPN 7 on human endometrial stromal cell (hESC) migration and invasion. Methods Western blotting and quantitative real-time PCR were used to detect the expression of CAPN 7 in endometriosis patients and normal fertile women. Scratch-wound-healing and invasion chamber assay were used to investigate the role of CAPN 7 in hESC migration and invasion. Western blotting, quantitative real-time PCR and zymography were carried out to detect the effect of CAPN 7 on the expressions and activity of MMP-2. Results CAPN 7 was markedly up-regulated in endometriosis, thereby promoting the migration and invasion of hESC. CAPN 7 overexpression led to increased expression of MMP-2 and tissue inhibitor of metalloproteinases 2 (TIMP-2); CAPN 7 knockdown reversed these changes. CAPN 7 increased MMP-2 activity by increasing the ratio of MMP-2 to TIMP-2. We also found that OA-Hy (an MMP-2 inhibitor) decreased the effects of CAPN 7 overexpression on hESC migration and invasion by approximately 50% and 55%, respectively. Additionally, a coimmunoprecipitation assay demonstrated that CAPN 7 interacted with activator protein 2α (AP-2α): an important transcription factor of MMP-2. Conclusions CAPN 7 promotes hESC migration and invasion by increasing the activity of MMP-2 via an increased ratio of MMP-2 to TIMP-2. PMID:23855590

  8. Glucose-regulated protein 94 deficiency induces squamous cell metaplasia and suppresses PTEN-null driven endometrial epithelial tumor development.

    PubMed

    Shen, Jieli; Yao, Lijing; Lin, Yvonne G; DeMayo, Francesco J; Lydon, John P; Dubeau, Louis; Lee, Amy S

    2016-03-22

    Endometrial carcinoma is the most prevalent gynecologic cancer in the United States. The tumor suppressor gene Pten (phosphatase and tensin homolog) is commonly mutated in the more common type 1 (endometrioid) subtype. The glucose-regulated protein 94 (GRP94) is emerging as a novel regulator for cancer development. Here we report that expression profiles from the Cancer Genome Atlas (TCGA) showed significantly increased Grp94 mRNA levels in endometrial tumor versus normal tissues, correlating with highly elevated GRP94 protein expression in patient samples and the requirement of GRP94 for maintaining viability of human endometrioid adenocarcinoma (EAC) cell lines. Through generation of uterus-specific knockout mouse models with deletion of Grp94 alone (c94f/f) or in combination with Pten (cPf/f94f/f), we discovered that c94f/f uteri induced squamous cell metaplasia (SCM) and reduced active nuclear β-catenin. The cPf/f94f/f uteri showed accelerated SCM and suppression of PTEN-null driven EAC, with reduced cellular proliferation, attenuated β-catenin signaling and decreased AKT/S6 activation in the SCM. In contrast to single PTEN knockout uteri (cPf/f), cPf/f94f/f uteri showed no decrease in E-cadherin level and no invasive lesion. Collectively, our study implies that GRP94 downregulation induces SCM in EAC and suppresses AKT/S6 signaling, providing a novel mechanism for suppressing EAC progression. PMID:26910913

  9. Thalidomide in Treating Patients With Recurrent or Persistent Endometrial Cancer

    ClinicalTrials.gov

    2013-01-23

    Endometrial Adenoacanthoma; Endometrial Adenocarcinoma; Endometrial Adenosquamous Cell Carcinoma; Endometrial Clear Cell Carcinoma; Endometrial Papillary Serous Carcinoma; Recurrent Endometrial Carcinoma

  10. Endometrial Ablation

    MedlinePlus

    ... a thin layer of the lining of the uterus and stops the menstrual flow in many women. ... medical conditions, including the following: • Disorders of the uterus or endometrium • Endometrial hyperplasia • Cancer of the uterus • ...

  11. Endometrial Cancer

    MedlinePlus

    Member Login Join Pay Dues Follow us: Women's Health Care Physicians Contact Us My ACOG ACOG Departments Donate ... and is best made in consultation with your health care team. What happens after treatment for endometrial cancer? ...

  12. Endometrial Cancer

    MedlinePlus

    ... having diabetes. Using estrogen replacement therapy without taking progestin may also increase the risk for endometrial cancer. ... take a combination of estrogen and the hormone progestin. While estrogen stimulates growth of the endometrium, progestin ...

  13. Endometrial biopsy

    MedlinePlus

    ... Abnormal menstrual periods may be caused by: Uterine fibroids Fingerlike growths in the uterus (uterine polyps) Infection ... More Cancer Endometrial cancer Endometritis Infertility Menopause Uterine fibroids Vaginal bleeding - hormonal Update Date 9/26/2015 ...

  14. Endometrial cancer

    MedlinePlus

    ... endometrial polyps Infrequent periods Never being pregnant Obesity Polycystic ovary syndrome (PCOS) Starting menstruation at an early age (before age ... Epithelium High blood ... Hysterectomy - abdominal - discharge Hysterectomy - laparoscopic - discharge ...

  15. YAP/TAZ regulates the insulin signaling via IRS1/2 in endometrial cancer

    PubMed Central

    Wang, Chao; Jeong, Kangjin; Jiang, Hongyuan; Guo, Wei; Gu, Chao; Lu, Yiling; Liang, Jiyong

    2016-01-01

    Insulin resistance (IR) is an important mechanism of pathogenesis of endometrial cancer (EC) and explains the pathogenic mechanism of high risk factors including Obesity BMI (body mass index), Type 2 Diabetes Mellitus, PCOS and so on. Relieving IR or inhibiting the function of insulin could be one of the potential therapeutic strategies for EC, which is a PI3K-driven disease. PI3K/Akt are the central mediators for insulin/IGF1 signaling, however, the involvement of HIPPO pathway co-activators, YAP and TAZ, in insulin resistance remains to be elucidated. In the present study, we analyzed the clinical and biological data of EC patients from TCGA and observed a correlation between insulin resistance and EC. By comparing the expression level of IRS1/2 in obese vs non-obese patients, we found that the most important insulin resistance relative (IRR) genes are the contributing factors to IR. Interestingly, IRS1/2 was correlated positively with YAP/TAZ in EC patients. Knockdown of YAP/TAZ by specific siRNA inhibited the phosphorylation of IRS1 while increased the phosphorylation of IGFR1, the inhibitor of insulin signaling. Treating EC with siYAP/TAZ, YAP inhibitor Verteporfin or metformin alone only partially inhibited the function of insulin and IGF1. However, combination of siYAP/TAZ with metformin could completely inhibit the effects of insulin. Thus, our study demonstrated a novel function of YAP and TAZ in the insulin resistance via IRS1/2 in endometrial cancer. Our study also provided the rationale for the potential therapeutic treatment of EC with the combination of inhibiting YAP/TAZ and metformin. PMID:27293994

  16. Macrophage migration inhibitory factor up-regulates alpha(v)beta(3) integrin and vascular endothelial growth factor expression in endometrial adenocarcinoma cell line Ishikawa.

    PubMed

    Bondza, Patrick Kibangou; Metz, Christine N; Akoum, Ali

    2008-04-01

    Human endometrium undergoes a series of dynamic physiological changes during the menstrual cycle of reproductive age women. Many factors, including hormones, cytokines, growth factors, matrix metalloproteinases and integrins, are essential for the success of embryonic implantation into endometrial tissue. Herein, we used a well-differentiated endometrial adenocarcinoma cell line, Ishikawa, to investigate in vitro the role played by macrophage migration inhibitory factor (MIF) in the regulation of endometrial receptivity markers. Quantitative real-time polymerase chain reaction (qRT-PCR) showed that MIF induced a slight increase in alpha(v) (alphav) mRNA integrin subunit expression during the first 12h, but reached a significant difference after 24h MIF treatment compared to control, whereas beta(3) (beta3) integrin subunit displayed significant increase in mRNA 2h following treatment. Immunocytofluorescence showed strong alphav and beta3 immunostaining at 25 ng/ml MIF, and Western blotting clearly indicated increased alphav and beta3 protein expression. MIF treatment significantly stimulated vascular endothelial growth factor (VEGF) mRNA expression in a dose- and time-dependent manner after 24 h treatment. Moreover, immunocytofluorescence revealed positive VEGF immunostaining compared to control, and analysis by ELISA of VEGF release in culture supernatants demonstrated that MIF (25 ng/ml) significantly induced VEGF secretion at 12 and 24 h. In conclusion, this study provides evidence that MIF directly up-regulates alphavbeta3 integrin and VEGF expression in human endometrial Ishikawa cells and may advance our understanding of factors involved in the establishment of endometrial receptivity and successful implantation. PMID:17854909

  17. Implementing A Mental Wellness Fast: An Intervention Strategy for Regulating the Negative Inner Dialogue

    ERIC Educational Resources Information Center

    Holland, Rochelle

    2006-01-01

    The purpose of this case study was to examine the efficacy of a developing technique that has been coined by this author as a Mental Wellness Fast. Therefore, this paper has been written for therapists who utilize spirituality and/or religion into their practice. The technique is geared to assist clients with healing poor inner dialogues and it…

  18. Bioinformatic detection of E47, E2F1 and SREBP1 transcription factors as potential regulators of genes associated to acquisition of endometrial receptivity

    PubMed Central

    2011-01-01

    Background The endometrium is a dynamic tissue whose changes are driven by the ovarian steroidal hormones. Its main function is to provide an adequate substrate for embryo implantation. Using microarray technology, several reports have provided the gene expression patterns of human endometrial tissue during the window of implantation. However it is required that biological connections be made across these genomic datasets to take full advantage of them. The objective of this work was to perform a research synthesis of available gene expression profiles related to acquisition of endometrial receptivity for embryo implantation, in order to gain insights into its molecular basis and regulation. Methods Gene expression datasets were intersected to determine a consensus endometrial receptivity transcript list (CERTL). For this cluster of genes we determined their functional annotations using available web-based databases. In addition, promoter sequences were analyzed to identify putative transcription factor binding sites using bioinformatics tools and determined over-represented features. Results We found 40 up- and 21 down-regulated transcripts in the CERTL. Those more consistently increased were C4BPA, SPP1, APOD, CD55, CFD, CLDN4, DKK1, ID4, IL15 and MAP3K5 whereas the more consistently decreased were OLFM1, CCNB1, CRABP2, EDN3, FGFR1, MSX1 and MSX2. Functional annotation of CERTL showed it was enriched with transcripts related to the immune response, complement activation and cell cycle regulation. Promoter sequence analysis of genes revealed that DNA binding sites for E47, E2F1 and SREBP1 transcription factors were the most consistently over-represented and in both up- and down-regulated genes during the window of implantation. Conclusions Our research synthesis allowed organizing and mining high throughput data to explore endometrial receptivity and focus future research efforts on specific genes and pathways. The discovery of possible new transcription factors

  19. Gonadotropin-releasing hormone type II (GnRH-II) agonist regulates the motility of human decidual endometrial stromal cells: possible effect on embryo implantation and pregnancy.

    PubMed

    Wu, Hsien-Ming; Huang, Hong-Yuan; Lee, Chyi-Long; Soong, Yung-Kuei; Leung, Peter C K; Wang, Hsin-Shih

    2015-04-01

    Invasion of the maternal decidua by extravillous trophoblast is an important process for embryo implantation and placentation in humans. Motile behavior of decidual endometrial stromal cells has been considered of critical importance for embryo implantation and programming of human pregnancy. The gonadotropin-releasing hormone (GnRH) effects in endometrium have raised concerns in reproduction. In the present study, we examined the action of GnRH-II agonist-promoted motility of human decidual endometrial stromal cells and the mechanisms of the action, indicating the role of GnRH-II agonist in embryo implantation and early pregnancy. Human decidual endometrial stromal cells were isolated from the decidual tissue from healthy women undergoing elective pregnancy termination of a normal pregnancy at 6- to 12-wk gestation, after informed consent. Cell motility was estimated by invasion and migration assay. Zymography and immunoblot analysis were performed to investigate the mechanisms of the GnRH-II action. The GnRH-I receptor (GnRH-IR) was expressed in human decidual tissue and endometrial stromal cells. The GnRH-II agonist promoted cell motility. Mitogen-activated protein kinase inhibitors abolished GnRH-II agonist-induced cell motility and activation of MMP-2 and MMP-9. GnRH-II agonist-mediated cell motility was suppressed by knockdown of endogenous GnRH-IR, MMP (matrix metalloproteinase)-2, and MMP-9 with small interfering RNA and MMP inhibitors. Our study demonstrates that the GnRH-II agonist promoted the cell motility of human decidual endometrial stromal cells through the GnRH-IR and the phosphorylation of extracellular signal-regulated protein kinase 1/2 and JNK-dependent activation of MMP-2 and MMP-9. Our findings represent a new concept regarding the mechanisms of GnRH-II-promoted cell motility, suggesting that GnRH-II agonist has strong effects on embryo implantation and decidual programming of human pregnancy. PMID:25761596

  20. Megestrol Acetate or Levonorgestrel-Releasing Intrauterine System in Treating Patients With Atypical Endometrial Hyperplasia or Endometrial Cancer

    ClinicalTrials.gov

    2014-09-09

    Atypical Endometrial Hyperplasia; Endometrial Adenocarcinoma; Recurrent Endometrial Carcinoma; Stage IA Endometrial Carcinoma; Stage IB Endometrial Carcinoma; Stage II Endometrial Carcinoma; Stage IIIA Endometrial Carcinoma; Stage IIIB Endometrial Carcinoma; Stage IIIC Endometrial Carcinoma; Stage IVA Endometrial Carcinoma; Stage IVB Endometrial Carcinoma

  1. FOXO1 is Required for Binding of PR on IRF4, Novel Transcriptional Regulator of Endometrial Stromal Decidualization

    PubMed Central

    Vasquez, Yasmin M.; Mazur, Erik C.; Li, Xilong; Kommagani, Ramakrishna; Jiang, Lichun; Chen, Rui; Lanz, Rainer B.; Kovanci, Ertug; Gibbons, William E.

    2015-01-01

    The forkhead box O1A (FOXO1) is an early-induced target of the protein kinase A pathway during the decidualization of human endometrial stromal cells (HESCs). In this study we identified the cistrome and transcriptome of FOXO1 and its role as a transcriptional regulator of the progesterone receptor (PR). Direct targets of FOXO1 were identified by integrating RNA sequencing with chromatin immunoprecipitation followed by deep sequencing. Gene ontology analysis demonstrated that FOXO1 regulates a subset of genes in decidualization such as those involved in cancer, p53 signaling, focal adhesions, and Wnt signaling. An overlap of the FOXO1 and PR chromatin immunoprecipitation followed by deep sequencing intervals revealed the co-occupancy of FOXO1 in more than 75% of PR binding intervals. Among these intervals were highly enriched motifs for the interferon regulatory factor member 4 (IRF4). IRF4 was determined to be a genomic target of both FOXO1 and PR and also to be differentially regulated in HESCs treated with small interfering RNA targeting FOXO1 or PR prior to decidualization stimulus. Ablation of FOXO1 was found to abolish binding of PR to the shared binding interval downstream of the IRF4 gene. Finally, small interfering RNA-mediated ablation of IRF4 was shown to compromise morphological transformation of decidualized HESCs and to attenuate the expression of the decidual markers IGFBP1, PRL, and WNT4. These results provide the first evidence that FOXO1 is functionally required for the binding of PR to genomic targets. Most notably, FOXO1 and PR are required for the regulation of IRF4, a novel transcriptional regulator of decidualization in HESCs. PMID:25584414

  2. Models of Persuasion Dialogue

    NASA Astrophysics Data System (ADS)

    Prakken, Henry

    This chapter1 reviews formal dialogue systems for persuasion. In persuasion dialogues two or more participants try to resolve a conflict of opinion, each trying to persuade the other participants to adopt their point of view. Dialogue systems for persuasion regulate how such dialogues can be conducted and what their outcome is. Good dialogue systems ensure that conflicts of view can be resolved in a fair and effective way [6]. The term ‘persuasion dialogue’ was coined by Walton [13] as part of his influential classification of dialogues into six types according to their goal. While persuasion aims to resolve a difference of opinion, negotiation tries to resolve a conflict of interest by reaching a deal, information seeking aims at transferring information, deliberationdeliberation wants to reach a decision on a course of action, inquiry is aimed at “growth of knowledge and agreement” and quarrel is the verbal substitute of a fight. This classification leaves room for shifts of dialogues of one type to another. In particular, other types of dialogues can shift to persuasion when a conflict of opinion arises. For example, in information-seeking a conflict of opinion could arise on the credibility of a source of information, in deliberation the participants may disagree about likely effects of plans or actions and in negotiation they may disagree about the reasons why a proposal is in one’s interest.

  3. Forkhead-box A1 induces cell senescence in endometrial cancer by regulating p16INK4a.

    PubMed

    Wang, Jingyun; Bian, Yiding; Liao, Yun; Xia, Ye; Wan, Xiaoping

    2016-08-01

    We previously identified FOXA1 as a tumor-suppressor in EC cells. In the present study, we sought to delineate the different roles of FOXA1 associated with cell senescence and further investigated the correlation between FOXA1 and p16INK4a in the progression of EC. Using reverse transcription-quantitative PCR (RT-qPCR), we found that FOXA1 expression was significantly downregulated in EC cells compared to that in normal endometrial cells. Functionally, senescence‑associated β-galactosidase staining, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), clonogenic and Transwell assays showed that in addition to acting as a pioneer factor, FOXA1 was significantly upregulated in senescent EC cells. Furthermore, restoration of FOXA1 expression triggered multiple steps of cellular senescence in EC cells and activated p16INK4a expression. All of these findings indicate that FOXA1 promotes cell senescence in EC by interaction with p16INK4a, possibly via the AKT pathway. Notably, a selective PI3K inhibitor raised the possibility that FOXA1‑induced senescence is associated with the AKT pathway in EC cells. Collectively, the present study provides a conceivable molecular mechanism by which cell senescence acts as the barrier to EC, and is regulated by FOXA1-induced p16INK4a expression. This may be a newly identified regulatory mechanism of cell senescence in EC. PMID:27349269

  4. Progesterone-dependent Regulation of Endometrial Cannabinoid Receptor Type 1 (CB1-R) Expression is Disrupted in Women with Endometriosis and in Isolated Stromal Cells Exposed to TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin)

    PubMed Central

    Resuehr, David; Glore, Dana R.; Taylor, Hugh S.; Bruner-Tran, Kaylon L.; Osteen, Kevin G.

    2012-01-01

    Objective To examine the differentiation-related expression of CB1-R mRNA and protein in endometrial tissue obtained from women with and without endometriosis and to determine the impact of acute TCDD exposure on CB1-R gene expression in isolated endometrial stromal cells. Design Laboratory-based study Setting University-affiliated medical center Patients Women with and without endometriosis undergoing volunteer endometrial biopsies after informed consent. Interventions None Main Outcome Measures Analysis of in vivo CB1-R mRNA and protein expression in human endometrial tissues and mRNA expression in isolated stromal cells following exposure to TCDD or a progesterone receptor antagonist (Onapristone). Results CB1-R mRNA and protein expression was highest during the progesterone-dominated secretory phase in control women, while expression was minimal in endometrial tissues acquired from women with endometriosis, regardless of the cycle phase. Although progesterone was found to induce CB1-R mRNA expression in endometrial stromal cells from control donors, steroid-induced expression of this gene was inhibited by co-treatment with either TCDD or Onapristone. Conclusions Our studies reveal a role for the anti-inflammatory actions of progesterone in regulating endometrial cannabinoid signaling, which is disrupted in women with endometriosis. Significantly, our studies demonstrate, for the first time, that acute TCDD exposure disrupts cannabinoid signaling in the human endometrium. PMID:22789143

  5. Lentiviral vector-mediated down-regulation of Notch1 in endometrial stem cells results in proliferation and migration in endometriosis.

    PubMed

    He, Hong; Liu, Rong; Xiong, Wei; Pu, Demin; Wang, Shixuan; Li, Tian

    2016-10-15

    The recent characterization of stem/progenitor cells in the endometrium has shed new light for pathogenesis of endometriosis. The present study was undertaken to investigate the role of Notch1, known as a cell fate regulator, in the mechanism of endometriosis. Influence of Notch1 on endometrial stem cells proliferation and migration was evaluated by knocking down Notch1 expression using shRNA. Furthermore, human endometrial stromal and epithelial stem cells with or without LV-Notch1-shRNA were injected into the peritoneal cavity of nude mice, to assess the in vivo effects of a specific antagonist of Notch1 on the progression of endometriosis. The results showed that LV-Notch1-shRNA led to a significant decline of clonogenicity and migration in human endometrial stem cells in vitro, as well as the size of endometriotic lesions in murine models. These data provide evidence that specific inhibition of Notch1 alters endometriotic tissue growth and progression, and may represent a promising potential therapeutic avenue. PMID:27389878

  6. MicroRNA-29b inhibits TGF-β1-induced fibrosis via regulation of the TGF-β1/Smad pathway in primary human endometrial stromal cells

    PubMed Central

    LI, JINGXIONG; CEN, BOHONG; CHEN, SIPING; HE, YUANLI

    2016-01-01

    Transforming growth factor (TGF)-β1 has a key role in the regulation of fibrosis and organ dysfunction. During the pathogenesis and progression of vital organ fibrosis, the microRNA (miR)-29 family is irregularly downregulated and exogenous supplementation of miR-29b has a strong anti-fibrotic capacity. However, whether TGF-β1 is able to provoke endometrial fibrosis, and the role of miR-29 in endometrial fibrosis remain unclear. In the present study, RT-qPCR, immunocytochemistry, western blot analysis, scanning electron microscopy, immunofluorescence staining, cell proliferation assay and flow cytometric analysis were employed. The results demonstrated that the expression levels of collagen, type 1, alpha 1 (COL1A1), α-smooth muscle actin (α-SMA) and phosphorylated (p)-Smad2/3 were increased, whereas miR-29b and maternally expressed gene 3 (MEG3) were decreased in primary endometrial stromal cells (ESCs) in response to TGF-β1 stimulation, in a time and dose-dependent manner. Furthermore, overexpression of miR-29b markedly reduced the expression levels of COL1A1 and α-SMA, and decreased the expression and nuclear accumulation of p-Smad2/3. In addition, ectopic overexpression of miR-29b increased the expression levels of MEG3, inhibited myofibroblast-like cell proliferation and induced apoptosis. These findings indicated that miR-29b may have a significant anti-fibrotic role, and may attenuate TGF-β1-induced fibrosis in ESCs. Therefore, exogenous miR-29b may serve as a potential therapeutic agent for the treatment of endometrial fibrosis. PMID:27035110

  7. LeftyA sensitive cytosolic pH regulation and glycolytic flux in Ishikawa human endometrial cancer cells

    SciTech Connect

    Salker, Madhuri S.; Zhou, Yuetao; Singh, Yogesh; Brosens, Jan; Lang, Florian

    2015-05-08

    Objective: LeftyA, a powerful regulator of stemness, embryonic differentiation, and reprogramming of cancer cells, counteracts cell proliferation and tumor growth. Key properties of tumor cells include enhanced glycolytic flux, which is highly sensitive to cytosolic pH and thus requires export of H{sup +} and lactate. H{sup +} extrusion is in part accomplished by Na{sup +}/H{sup +} exchangers, such as NHE1. An effect of LeftyA on transport processes has, however, never been reported. The present study thus explored whether LeftyA modifies regulation of cytosolic pH (pHi) in Ishikawa cells, a well differentiated endometrial carcinoma cell model. Methods: NHE1 transcript levels were determined by qRT-PCR, NHE1 protein abundance quantified by Western blotting, pH{sub i} estimated utilizing (2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein [BCECF] fluorescence, Na{sup +}/H{sup +} exchanger activity from Na{sup +} dependent realkalinization after an ammonium pulse, and lactate concentration in the supernatant utilizing an enzymatic assay and subsequent colorimetry. Results: A 2 h treatment with LeftyA (8 ng/ml) significantly decreased NHE1 transcript levels (by 99.6%), NHE1 protein abundance (by 71%), Na{sup +}/H{sup +} exchanger activity (by 55%), pHi (from 7.22 ± 0.02 to 7.05 ± 0.02), and lactate release (by 41%). Conclusions: LeftyA markedly down-regulates NHE1 expression, Na{sup +}/H{sup +} exchanger activity, pHi, and lactate release in Ishikawa cells. Those effects presumably contribute to cellular reprogramming and growth inhibition. - Highlights: • LeftyA, an inhibitor of tumor growth, reduces Na{sup +}/H{sup +}-exchanger activity by 55%. • LeftyA decreases NHE1 transcripts by 99.6% and NHE1 protein by 71%. • LeftyA decreases cytosolic pH from 7.22 ± 0.02 to 7.05 ± 0.02. • Cytosolic acidification by Lefty A decreases glycolysis by 41%. • Cytosolic acidification by Lefty A compromises energy production of tumor cells.

  8. Stromal Clues in Endometrial Carcinoma: Loss of Expression of β-Catenin, Epithelial-Mesenchymal Transition Regulators, and Estrogen-Progesterone Receptor

    PubMed Central

    Sayar, Ilyas; Ceyran, Ayse B.; Ibiloglu, Ibrahim; Akalin, Ibrahim; Firat, Ugur; Kosemetin, Duygu; Engin Zerk, Pinar; Aydin, Abdullah

    2016-01-01

    Epithelial-stroma interactions in the endometrium are known to be responsible for physiological functions and emergence of several pathologic lesions. Periglandular stromal cells act on endometrial cells in a paracrine manner through sex hormones. In this study, we immunohistochemically evaluated the expression of epithelial-mesenchymal transition regulators (SNAIL/SLUG, TWIST, ZEB1), adhesion molecules (β-catenin and E-cadhenin), estrogen (ER)-progesterone (PR) receptor and their correlation with each other in 30 benign, 148 hyperplastic (EH), and 101 endometrioid-type endometrial carcinoma (EC) endometria. In the epithelial component, loss of expression in E-cadherin, ER and PR, and overexpression of TWIST and ZEB1 were significantly higher in EC than in EH (P<0.01). In the periglandular stromal component, β-catenin and SNAIL/SLUG expression were significantly higher in normal endometrium and simple without atypical EH compared with complex atypical EH and EC (P<0.01). In addition, periglandular stromal TWIST expression was significantly higher in EH group compared with EC (P<0.05). There was significantly negative correlation between β-catenin and ER, TWIST and ER, and TWIST and PR in hyperplastic and carcinomatous glandular epithelium, whereas there was a significantly positive correlation between β-catenin and SNAIL-SLUG, β-catenin and TWIST, β-catenin and ER, β-catenin and PR, SNAIL-SLUG and ER, SNAIL-SLUG and PR, TWIST and ER, TWIST and PR, in periglandular/cancer-associated stromal cells (P<0.01). In conclusion, the pattern of positive and negative correlations in the expression of epithelial-mesenchymal transition regulators (SNAIL-SLUG and TWIST), sex hormone receptors (ER and PR), and β-catenin between ECs and hyperplasia, as well as between epithelium and stroma herein, is suggestive of a significant role for these proteins and their underlying molecular processes in the development of endometrial carcinomas. PMID:26367784

  9. Dialogue and Structure: Enabling Learner Self-Regulation in Technology-Enhanced Learning Environments

    ERIC Educational Resources Information Center

    Andrade, Maureen Snow

    2014-01-01

    Distance learning that incorporates technology-enhanced learning environments provides a solution to the ever-increasing global demand for higher education. To be successful in these contexts, learners must be self-regulated, or have the ability to control the factors affecting their learning. Based on the theories of transactional distance,…

  10. Determination of Heavy Metal Concentrations in Normal and Pathological Human Endometrial Biopsies and In Vitro Regulation of Gene Expression by Metals in the Ishikawa and Hec-1b Endometrial Cell Line

    PubMed Central

    Tomkiewicz, Céline; Leblanc, Alix; Pierre, Stéphane; El Balkhi, Souleiman; Le Frère-Belda, Marie-Aude; Lecuru, Fabrice; Poupon, Joël; Barouki, Robert; Aggerbeck, Martine; Coumoul, Xavier

    2015-01-01

    It is well known that several metals, such as lead, mercury, cadmium, and vanadium, can mimic the effects of estrogens (metallo-estrogens). Nevertheless, there are only a few studies that have assessed the effects of toxic metals on the female genital tract and, in particular, endometrial tissue. In this context, we measured the concentrations of several trace elements in human endometrial tissue samples from individuals with hyperplasia or adenocarcinoma and in normal tissues. Hyperplasic endometrial tissue has a 4-fold higher concentration of mercury than normal tissue. Mercury can affect both the AhR and ROS signaling pathways. Thus, we investigated the possible toxic effects of mercury by in vitro studies. We found that mercury increases oxidative stress (increased HO1 and NQO1 mRNA levels) and alters the cytoskeleton in the human endometrial Ishikawa cell line and to a lesser extent, in the “less-differentiated” human endometrial Hec-1b cells. The results might help to explain a potential link between this metal and the occurrence of endometrial hyperplasia. PMID:26600472

  11. What Is Endometrial Cancer?

    MedlinePlus

    ... endometrial adenocarcinomas. These types tend to be more aggressive than most endometrial cancers. They tend to grow ... forming glands. Grade 3 cancers tend to be aggressive and have a poorer outlook than lower-grade ...

  12. Endometrial cancer.

    PubMed

    Morice, Philippe; Leary, Alexandra; Creutzberg, Carien; Abu-Rustum, Nadeem; Darai, Emile

    2016-03-12

    Endometrial cancer is the most common gynaecological tumour in developed countries, and its incidence is increasing. The most frequently occurring histological subtype is endometrioid adenocarcinoma. Patients are often diagnosed when the disease is still confined to the uterus. Standard treatment consists of primary hysterectomy and bilateral salpingo-oophorectomy, often using minimally invasive approaches (laparoscopic or robotic). Lymph node surgical strategy is contingent on histological factors (subtype, tumour grade, involvement of lymphovascular space), disease stage (including myometrial invasion), patients' characteristics (age and comorbidities), and national and international guidelines. Adjuvant treatment is tailored according to histology and stage. Various classifications are used to assess the risks of recurrence and to determine optimum postoperative management. 5 year overall survival ranges from 74% to 91% in patients without metastatic disease. Trials are ongoing in patients at high risk of recurrence (including chemotherapy, chemoradiation therapy, and molecular targeted therapies) to assess the modalities that best balance optimisation of survival with the lowest adverse effects on quality of life. PMID:26354523

  13. Copanlisib in Treating Patients With Persistent or Recurrent Endometrial Cancer

    ClinicalTrials.gov

    2016-03-30

    Endometrial Endometrioid Adenocarcinoma; Endometrial Mixed Adenocarcinoma; Endometrial Serous Adenocarcinoma; Endometrial Undifferentiated Carcinoma; Metastatic Endometrioid Adenocarcinoma; Recurrent Uterine Corpus Carcinoma

  14. Role of Progesterone in Endometrial Cancer

    PubMed Central

    Kim, J. Julie; Chapman-Davis, Eloise

    2016-01-01

    Progesterone is a key hormone in the endometrium that opposes estrogen-driven growth. Insufficient progesterone will result in unopposed estrogen action that could lead to the development of endometrial hyperplasia and adenocarcinoma. Although these endometrial neoplasias can regress in response to progestin treatment, this does not occur in all instances. To understand this resistance to progesterone and to improve on existing hormonal therapies, it is imperative that the molecular mechanisms of progesterone action through its receptor be deciphered in endometrial cancer. This review highlights what is known thus far regarding the efficacy of progestin therapy in the clinic and the role of progesterone in endometrial cancer cell behavior and gene regulation. PMID:20104432

  15. Trebananib in Treating Patients With Persistent or Recurrent Endometrial Cancer

    ClinicalTrials.gov

    2016-02-10

    Endometrial Adenocarcinoma; Endometrial Adenosquamous Carcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Endometrioid Adenocarcinoma, Variant With Squamous Differentiation; Endometrial Serous Adenocarcinoma; Endometrioid Stromal Sarcoma; Recurrent Uterine Corpus Carcinoma

  16. Temsirolimus in Treating Patients With Metastatic or Locally Advanced Recurrent Endometrial Cancer

    ClinicalTrials.gov

    2015-02-05

    Endometrial Adenocarcinoma; Endometrial Adenosquamous Cell Carcinoma; Endometrial Clear Cell Carcinoma; Endometrial Papillary Serous Carcinoma; Recurrent Endometrial Carcinoma; Stage IIIA Endometrial Carcinoma; Stage IIIB Endometrial Carcinoma; Stage IIIC Endometrial Carcinoma; Stage IVA Endometrial Carcinoma; Stage IVB Endometrial Carcinoma

  17. Screening for Endometrial Cancer

    PubMed Central

    Nisker, Jeffrey A.

    1983-01-01

    Although population screening for cervical neoplasia is widely practiced, screening for endometrial neoplasia has only recently been considered. Before development of endometrial carcinoma, the endometrium undergoes progressive neoplastic alterations in a parallel fashion to the premalignant precursors of cervical carcinoma. Screening for endometrial carcinoma may be particularly appropriate because of the existence of a well defined, easily identifiable high risk group and tissue sampling techniques that are accurate, easy to perform, inexpensive, and well tolerated. Women at increased risk of endometrial carcinoma include: obese postmenopausal women, women on postmenopausal estrogen replacement therapy, premenopausal women with a history of anovulatory cycles (including women with polycystic ovarian disease) and women with hepatic cirrhosis. Using endometrial aspiration devices, screening for endometrial hyperplasia and carcinoma may be performed by any physician familiar with intrauterine contraceptive device insertion in the office. The impact of such routine screening of high risk women will be determined only after large screening studies have been accomplished. PMID:21283374

  18. Management of endometrial precancers.

    PubMed

    Trimble, Cornelia L; Method, Michael; Leitao, Mario; Lu, Karen; Ioffe, Olga; Hampton, Moss; Higgins, Robert; Zaino, Richard; Mutter, George L

    2012-11-01

    In the United States, endometrial cancer is the most commonly diagnosed cancer of the female reproductive system. Strategies to sensitively and accurately diagnose premalignant endometrial lesions are sorely needed. We reviewed studies pertaining to the diagnostic challenges of endometrial precancers, their predictive value, and evidence to support management strategies. Currently, two diagnostic schemas are in use: the four-class 1994 World Health Organization hyperplasia system, based on morphologic features of architectural complexity and nuclear atypia and, more recently, the two-class endometrial intraepithelial neoplasia system, which is quantitative. Diagnosis should use criteria and terminology that distinguish between clinicopathologic entities that can be managed differently. In some instances, such as for women with hereditary nonpolyposis colon cancer, biomarkers may aid in diagnosis, but the clinical utility of biomarkers has yet to be determined. Total hysterectomy is curative for atypical endometrial hyperplasia or endometrial intraepithelial neoplasia, and provides a definitive standard for assessment of a concurrent carcinoma, when clinically appropriate. If hysterectomy is performed for atypical endometrial hyperplasia or endometrial intraepithelial neoplasia, then intraoperative assessment of the uterine specimen for occult carcinoma is desirable, but optional. Nonsurgical management may be appropriate for patients who wish to preserve fertility or those for whom surgery is not a viable option. Treatment with progestin therapy may provide a safe alternative to hysterectomy; however, clinical trials of hormonal therapies for atypical endometrial hyperplasia or endometrial intraepithelial neoplasia have not yet established a standard regimen. Future studies will need to determine the optimal nonsurgical management of atypical endometrial hyperplasia or endometrial intraepithelial neoplasia, standardizing agent, dose, schedule, clinical outcomes

  19. Lysophosphatidic acid and sphingosine 1-phosphate metabolic pathways and their receptors are differentially regulated during decidualization of human endometrial stromal cells.

    PubMed

    Brünnert, D; Sztachelska, M; Bornkessel, F; Treder, N; Wolczynski, S; Goyal, P; Zygmunt, M

    2014-10-01

    In the luteal phase, human endometrial stromal cells (HESCs) undergo proliferation, migration and differentiation during the decidualization process under the control of the ovarian steroids progesterone and estrogen. Proper decidualization of stromal cells is required for blastocyst implantation and the development of pregnancy. The proliferation, migration and differentiation of HESCs in decidualization do not require the presence of a blastocyst but are greatly accelerated during implantation. Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are potent bioactive lysophospholipids that have critical roles in various physiological and pathophysiological processes, including inflammation, angiogenesis and cancer. The expression of the enzymes involved in LPA and S1P turnover and their receptors in HESCs during decidualization has not been characterized yet. We found that the LPAR1 and LPAR6 and S1PR3 receptors are highly expressed in HESCs. LPAR1, autotaxin (ATX), an LPA producing enzyme and lipid phosphate phosphatase 3 were up-regulated during decidualization. Interestingly, the expression of all S1P receptor subtypes and LPA receptors (LPAR2-6) mRNA was down-regulated after decidualization. We found that SPHK1 is highly expressed in HESCs, and is up-regulated during decidualization. S1P phosphatase SGPP1 and S1P lyase SGPL1 are highly expressed in HESCs. SGPP1 mRNA expression was significantly up-regulated in decidualized HESCs. In conclusion, this study shows the first time that specific LPA and S1P receptors and their metabolizing enzymes are highly regulated in HESCs during decidualization. Furthermore, we suggest that LPAR1 receptor-mediated signaling in HESCs may be crucial in decidualization process. SPHK1 activity and high turnover of S1P and LPA might be essential for precise regulation of their signaling during decidualization of human endometrium and implantation. PMID:24994816

  20. Trametinib With or Without GSK2141795 in Treating Patients With Recurrent or Persistent Endometrial Cancer

    ClinicalTrials.gov

    2016-08-24

    Endometrial Adenocarcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Mixed Adenocarcinoma; Endometrial Serous Adenocarcinoma; Endometrial Undifferentiated Carcinoma; Recurrent Uterine Corpus Carcinoma

  1. KDM4B and KDM4A promote endometrial cancer progression by regulating androgen receptor, c-myc, and p27kip1

    PubMed Central

    Kwan, Suet-Ying; Chen, Limo; Chen, Jin-Hong; Ying, Zuo-Lin; Zhou, Ye; Gu, Wei; Wang, Li-Hua; Cheng, Wei-Wei; Zeng, Jianfang; Wan, Xiao-Ping; Mok, Samuel C.; Wong, Kwong-Kwok; Bao, Wei

    2015-01-01

    Epidemiological evidence suggests that elevated androgen levels and genetic variation related to the androgen receptor (AR) increase the risk of endometrial cancer (EC). However, the role of AR in EC is poorly understood. We report that two members of the histone demethylase KDM4 family act as major regulators of AR transcriptional activityin EC. In the MFE-296 cell line, KDM4B and AR upregulate c-myc expression, while in AN3CA cells KDM4A and AR downregulate p27kip1. Additionally, KDM4B expression is positively correlated with AR expression in EC cell lines with high baseline AR expression, while KDM4A and AR expression are positively correlated in low-AR cell lines. In clinical specimens, both KDM4B and KDM4A expression are significantly higher in EC tissues than that in normal endometrium. Finally, patients with alterations in AR, KDM4B, KDM4A, and c-myc have poor overall and disease-free survival rates. Together, these findings demonstrate that KDM4B and KDM4A promote EC progression by regulating AR activity. PMID:26397136

  2. KDM4B and KDM4A promote endometrial cancer progression by regulating androgen receptor, c-myc, and p27kip1.

    PubMed

    Qiu, Mei-Ting; Fan, Qiong; Zhu, Zhu; Kwan, Suet-Ying; Chen, Limo; Chen, Jin-Hong; Ying, Zuo-Lin; Zhou, Ye; Gu, Wei; Wang, Li-Hua; Cheng, Wei-Wei; Zeng, Jianfang; Wan, Xiao-Ping; Mok, Samuel C; Wong, Kwong-Kwok; Bao, Wei

    2015-10-13

    Epidemiological evidence suggests that elevated androgen levels and genetic variation related to the androgen receptor (AR) increase the risk of endometrial cancer (EC). However, the role of AR in EC is poorly understood. We report that two members of the histone demethylase KDM4 family act as major regulators of AR transcriptional activityin EC. In the MFE-296 cell line, KDM4B and AR upregulate c-myc expression, while in AN3CA cells KDM4A and AR downregulate p27kip1. Additionally, KDM4B expression is positively correlated with AR expression in EC cell lines with high baseline AR expression, while KDM4A and AR expression are positively correlated in low-AR cell lines. In clinical specimens, both KDM4B and KDM4A expression are significantly higher in EC tissues than that in normal endometrium. Finally, patients with alterations in AR, KDM4B, KDM4A, and c-myc have poor overall and disease-free survival rates. Together, these findings demonstrate that KDM4B and KDM4A promote EC progression by regulating AR activity. PMID:26397136

  3. MiR-125b regulates endometrial receptivity by targeting MMP26 in women undergoing IVF-ET with elevated progesterone on HCG priming day.

    PubMed

    Chen, Cheng; Zhao, Yue; Yu, Yang; Li, Rong; Qiao, Jie

    2016-01-01

    On the women undergoing IVF-ET with elevated progesterone on human chorionic gonadotrophin priming, the assisted reproductive technology outcome is poor. But, due to the unknown mechanism of this process, no effective method has been found to overcome this difficulty. Here, we investigated the roles of miR-125b and its target gene, MMP26, in endometrial receptivity (ER) in these women. The expression of miR-125b was significantly up-regulated in EECs in women with elevated progesterone during the window of implantation, and it showed a progesterone-dependent effect in vitro. Similarly, the expression of miR-125b was significantly up-regulated in the preimplantation period, and was down-regulated in the implantation period and the post-implantation period in mouse EECs. In addition, miR-125b showed a greater decrease at implantation sites than it did at interimplantation sites. The luciferase report assay demonstrated that MMP26 is a target gene of miR-125b. And the expression profile of MMP26 showed an inverse relationship with miR-125b in vivo and in vitro. Overexpression of miR-125b in human EECs inhibited cell migration and invasion. Gain-of-function of miR-125b induced a significant decrease in the number of implantation sites. In conclusion, these data shed new light on how miR-125b triggers ER decline through the regulation of MMP26 function. PMID:27143441

  4. MiR-125b regulates endometrial receptivity by targeting MMP26 in women undergoing IVF-ET with elevated progesterone on HCG priming day

    PubMed Central

    Chen, Cheng; Zhao, Yue; Yu, Yang; Li, Rong; Qiao, Jie

    2016-01-01

    On the women undergoing IVF-ET with elevated progesterone on human chorionic gonadotrophin priming, the assisted reproductive technology outcome is poor. But, due to the unknown mechanism of this process, no effective method has been found to overcome this difficulty. Here, we investigated the roles of miR-125b and its target gene, MMP26, in endometrial receptivity (ER) in these women. The expression of miR-125b was significantly up-regulated in EECs in women with elevated progesterone during the window of implantation, and it showed a progesterone-dependent effect in vitro. Similarly, the expression of miR-125b was significantly up-regulated in the preimplantation period, and was down-regulated in the implantation period and the post-implantation period in mouse EECs. In addition, miR-125b showed a greater decrease at implantation sites than it did at interimplantation sites. The luciferase report assay demonstrated that MMP26 is a target gene of miR-125b. And the expression profile of MMP26 showed an inverse relationship with miR-125b in vivo and in vitro. Overexpression of miR-125b in human EECs inhibited cell migration and invasion. Gain-of-function of miR-125b induced a significant decrease in the number of implantation sites. In conclusion, these data shed new light on how miR-125b triggers ER decline through the regulation of MMP26 function. PMID:27143441

  5. Management of Endometrial Precancers

    PubMed Central

    Trimble, Cornelia L.; Method, Michael; Leitao, Mario; Lu, Karen; Ioffe, Olga; Hampton, Moss; Higgins, Robert; Zaino, Richard; Mutter, George L.

    2013-01-01

    In the United States, endometrial cancer is the most commonly diagnosed cancer of the female reproductive system. Strategies to sensitively and accurately diagnose premalignant endometrial lesions are sorely needed. We reviewed studies pertaining to the diagnostic challenges of endometrial precancers, their predictive value, and evidence to support management strategies. Currently, two diagnostic schema are in use; the 4-class WHO94 hyperplasia system, based on morphologic features of architectural complexity and nuclear atypia, and more recently, the 2-class endometrial intraepithelial neoplasia system, which is quantitative. Diagnosis should employ criteria and terminology which distinguish between clinicopathologic entities that can be managed differently. In some instances, such as for women with hereditary nonpolyposis colon cancer (HNPCC), biomarkers may aid in diagnosis, but the clinical utility of biomarkers has yet to be determined. Total hysterectomy is curative for atypical endometrial hyperplasia or endometrial intraepithelial neoplasia, and provides a definitive standard for assessment of a concurrent carcinoma, where clinically appropriate. If hysterectomy is performed for atypical endometrial hyperplasia or endometrial intraepithelial neoplasia, intraoperative assessment of the uterine specimen for occult carcinoma is desirable, but optional. Nonsurgical management may be appropriate for patients who wish to preserve fertility or those for whom surgery is not a viable option. Treatment with progestin therapy may provide a safe alternative to hysterectomy; however, clinical trials of hormonal therapies for atypical endometrial hyperplasia or endometrial intraepithelial neoplasia have not yet established a standard regimen. Future studies will need to determine the optimal non-surgical management of AEH/EIN, standardizing agent, dose, schedule, clinical outcomes, and appropriate follow-up. PMID:23090535

  6. Activin B induces human endometrial cancer cell adhesion, migration and invasion by up-regulating integrin β3 via SMAD2/3 signaling

    PubMed Central

    Xiong, Siyuan; Klausen, Christian; Cheng, Jung-Chien; Zhu, Hua; Leung, Peter C.K.

    2015-01-01

    Endometrial cancer is the fourth most common female cancer and the most common gynecological malignancy. Although it comprises only ~10% of all endometrial cancers, the serous histological subtype accounts for ~40% of deaths due to its aggressive behavior and propensity to metastasize. Histopathological studies suggest that elevated expression of activin/inhibin βB subunit is associated with reduced survival in non-endometrioid endometrial cancers (type II, mostly serous). However, little is known about the specific roles and mechanisms of activin (βB dimer) in serous endometrial cancer growth and progression. In the present study, we examined the biological functions of activin B in type II endometrial cancer cell lines, HEC-1B and KLE. Our results demonstrate that treatment with activin B increases cell migration, invasion and adhesion to vitronectin, but does not affect cell viability. Moreover, we show that activin B treatment increases integrin β3 mRNA and protein levels via SMAD2/3-SMAD4 signaling. Importantly, siRNA knockdown studies revealed that integrin β3 is required for basal and activin B-induced cell migration, invasion and adhesion. Our results suggest that activin B-SMAD2/3-integrin β3 signaling could contribute to poor patient survival by promoting the invasion and/or metastasis of type II endometrial cancers. PMID:26384307

  7. Dialogue and Team Teaching

    ERIC Educational Resources Information Center

    Game, Ann; Metcalfe, Andrew

    2009-01-01

    Although dialogue is a common word in educational theory, its full significance is diluted if it is seen as a matter of exchange or negotiation of prior intellectual positions. In fact, the "dia"- of dialogue indicates "through": dialogue moves through participants and they through it. Dialogue allows participants to have thoughts they could not…

  8. Distinct Characteristics of Endometrial and Decidual Macrophages and Regulation of Their Permissivity to HIV-1 Infection by SAMHD1

    PubMed Central

    Quillay, Héloïse; El Costa, Hicham; Marlin, Romain; Duriez, Marion; Cannou, Claude; Chrétien, Fabrice; Fernandez, Hervé; Lebreton, Anne; Ighil, Julien; Schwartz, Olivier; Barré-Sinoussi, Françoise; Nugeyre, Marie-Thérèse

    2014-01-01

    ABSTRACT In order to develop strategies to prevent HIV-1 (human immunodeficiency virus type 1) transmission, it is crucial to better characterize HIV-1 target cells in the female reproductive tract (FRT) mucosae and to identify effective innate responses. Control of HIV-1 infection in the decidua (the uterine mucosa during pregnancy) can serve as a model to study natural mucosal protection. Macrophages are the main HIV-1 target cells in the decidua. Here we report that in vitro, macrophages and T cells are the main HIV-1 targets in the endometrium in nonpregnant women. As reported for decidual macrophages (dM), endometrial macrophages (eM) were found to have an M2-like phenotype (CD68+ CD163+ CD206+ IL-10high). However, eM and dM may belong to different subpopulations, as they differently express certain markers and secrete different amounts of proinflammatory and anti-inflammatory cytokines. We observed strong expression of the SAMHD1 restriction factor and weak expression of its inactive form (pSAMHD1, phosphorylated at residue Thr592) in both eM and dM. Infection of macrophages from both tissues was enhanced in the presence of the viral protein Vpx, suggesting a role for SAMHD1 in the restriction of HIV-1 infection. This study and further comparisons of the decidua with FRT mucosae in nonpregnant women should help to identify mechanisms of mucosal protection against HIV-1 infection. IMPORTANCE The female reproductive tract mucosae are major portals of HIV-1 entry into the body. The decidua (uterine mucosa during pregnancy) can serve as a model for studying natural mucosal protection against HIV-1 transmission. A comparison of target cells and innate responses in the decidua versus the endometrium in nonpregnant women could help to identify protective mechanisms. Here, we report for the first time that macrophages are one of the main HIV-1 target cells in the endometrium and that infection of macrophages from both the endometrium and the decidua is restricted by

  9. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) suppresses spheroids attachment on endometrial epithelial cells through the down-regulation of the Wnt-signaling pathway.

    PubMed

    Tsang, Hilda; Cheung, Tsz-Yan; Kodithuwakku, Suranga P; Chai, Joyce; Yeung, William S B; Wong, Chris K C; Lee, Kai-Fai

    2012-01-01

    The environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) affects embryo development, implantation and fertility in humans. The underlying molecular mechanism by which TCDD suppresses implantation remains largely unknown. We used the trophoblastic spheroids (embryo surrogate)-endometrial cells co-culture assay to study the attachment of trophoblastic spheroids (BeWo and Jeg-3) onto the endometrial epithelial (RL95-2 and Ishikawa) cells. TCDD dose-dependently induced cytochrome P450 1A1 (Cyp1A1) expression in trophoblastic and endometrial epithelial cells. Moreover, TCDD at 1 and 10 nM suppressed β-catenin (a Wnt-signaling molecule) and E-cadherin expression, as well as spheroids attachment onto endometrial cells. Interestingly, activation of the canonical Wnt-signaling pathway via Wnt3a or lithium chloride reverted the suppressive effect of TCDD on β-catenin and E-cadherin expressions in the BeWo and RL95-2 cells, and restored the spheroids attachment rate to be comparable to the untreated controls. Taken together, TCDD induces Cyp1A1 expression, modulates the Wnt-signaling pathway and suppresses spheroids attachment onto endometrial cells. PMID:22134133

  10. Effects of adipocyte-secreted factors on decidualized endometrial cells: modulation of endometrial receptivity in vitro.

    PubMed

    Gamundi-Segura, Silvia; Serna, Jose; Oehninger, Sergio; Horcajadas, Jose A; Arbones-Mainar, Jose M

    2015-09-01

    Obesity is defined as an excessive accumulation of adipose tissue that may lead to health complications. Mounting evidence indicates that obesity has a negative impact on fertility. Yet, the link between adipose tissue biology and infertility remains unclear. We aimed to investigate the communication between the adipose tissue and the reproductive system and the importance of this cross talk for the development of a receptive endometrium. To that end, we generated an in vitro model with endometrial and adipocyte cell lines. Sexual hormones, progesterone and estradiol, were used to decidualize endometrial cells and sensitize adipocytes. Decidualization produced a simultaneous increase of adipokine receptors in endometrial cells paralleling changes in their receptivity status. Furthermore, sensitization of 3T3-L1 adipocytes increased mRNA levels of leptin and resistin and decreased the expression of adiponectin and chemerin levels. This was accompanied by increased isoproterenol-induced lipolysis and reduced insulin-stimulated glucose uptake. Lastly, conditioned culture medium of those sensitized adipocytes was used to feed endometrial cells. This treatment resulted in (i) upregulation of genes previously identified as positive regulators of endometrial receptivity, such as leukemia inhibitory factor and glutathione peroxidase 3, and (ii) downregulation of interleukin-15 and mucin1, both genes negatively related with endometrial receptivity. Our results indicate that the endocrine communication between adipose tissue and the reproductive system is bidirectional and stress the importance of the adipose tissue to modulate the reproductive fitness. PMID:25686566

  11. Endometrial Cancer Risk Factors

    MedlinePlus

    ... Women with a condition called polycystic ovarian syndrome (PCOS) have abnormal hormone levels, such as higher androgen ( ... increase a woman's chance of getting endometrial cancer. PCOS is also a leading cause of infertility in ...

  12. CD82 expression alters with human endometrial cycles and affects the uterine endometrial receptivity in vitro.

    PubMed

    Wei, Xiaowei; Liu, Shuai; Wang, Xiaoqi; Yan, Qiu

    2012-03-01

    Embryo implantation is a process that requires both temporal and spatial synchronization of the uterine endometrium and the embryo, and the endometrium becomes receptive to the embryo during the window of implantation. Although the expression patterns of many implantation-related molecules change dynamically during this process, the impact of CD82 on endometrial receptivity has not been elucidated. By immunohistochemical staining, we found that CD82 levels rose from the proliferative phase to the secretory phase in human endometrium. Specifically, the highest level appeared in mid- and late-secretory phases. Consistently, RL95-2 cells, representative of high-receptive endometrial epithelium, expressed higher levels of CD82 than did HEC-1A cells, which are representative of low-receptive endometrial epithelium, as detected by reverse transcription-polymerase chain reaction, Western blot and immunofluorescence. Furthermore, progesterone up-regulated the expression of CD82 in both epithelial cell lines. Down-regulation of CD82 in RL95-2 cells by either CD82 siRNA transfection or treatment with a CD82 antibody significantly decreased the adhesion of human embryonic JAR cells to RL95-2 cell monolayers (P < 0.01) and inhibited the phosphorylation of focal adhesion kinase (FAK). In contrast, up-regulation of CD82 in HEC-1A cells by CD82 cDNA transfection promoted embryonic JAR cell adhesion to HEC-1A monolayers (P < 0.05) and activated the phosphorylation of FAK. In conclusion, the expression of CD82 increases in endometrial tissues during the window of embryo implantation, CD82 expression affects endometrial receptivity of the uterine epithelial cells in vitro, and the FAK signaling pathway may be involved in this phenomenon. The correlation between CD82 and endometrial receptivity suggests that CD82 may serve as a potential marker of endometrial function. PMID:22393164

  13. The endometrial hyperplasias revisited.

    PubMed

    Sivridis, Efthimios; Giatromanolaki, Alexandra

    2008-09-01

    The proliferating lesions in the endometrium form a morphological continuum extending from benign to malignant, through a transitional pre-invasive stage. Within this spectrum, several classifications of endometrial hyperplasia have been developed over the years in which the precancerous lesions gained a substantial distinction, although not without inconsistencies in definitions and terminology. The revised WHO 1994 classification explicitly recognizes cytological atypia as the defining feature for distinguishing genuine hyperplastic lesions (simple and complex endometrial hyperplasia) from those that are potentially precancerous (simple and complex atypical endometrial hyperplasia) and puts an end to the verbal anarchy by adopting a common language of communication. This taxonomy, however, was criticized for complexity and low level of reproducibility. Thus, in the name of improved reproducibility a new classification was recently proposed which (a) combines simple and complex endometrial hyperplasia within one diagnostic category known as endometrial hyperplasia and (b) defines new criteria for recognising the precancerous lesions: a monoclonal growth, known as endometrial intraepithelial neoplasia (EIN), comprising clusters of crowded glands, greater than 1 mm in diameter, having a cytologically altered epithelium. The EIN concept was challenged of not being independently tested and received with great enthusiasm by some scholars and relative skepticism by others. PMID:18726114

  14. Influence of Cancer-Associated Endometrial Stromal Cells on Hormone-Driven Endometrial Tumor Growth

    PubMed Central

    Pineda, M. J.; Lu, Z.; Cao, D.

    2016-01-01

    Cancer-associated fibroblasts have been shown to inhibit or stimulate tumor growth depending on stage, grade, and tumor type. It remains unclear, however, the effect of endometrial-cancer-associated fibroblasts on hormone-driven responses in endometrial cancer. In this study, we investigated the effect of normal and cancer-associated stromal cells from patients with and without endometrial cancer on endometrial tumor growth in response to estradiol (E2) and progesterone (P4). Compared to benign endometrial stromal cells, the low-grade and high-grade cancer-associated stromal cells exhibited a blunted hormone response for proliferation as well as IGFBP1 secretion. Additional analysis of the influence of stromal cells on hormone-driven tumor growth was done by mixing stromal cells from benign, low-grade, or high-grade tumors, with Ishikawa cells for subcutaneous tumor formation. The presence of both benign and high-grade cancer-associated stromal cells increased estradiol-driven xenografted tumor growth compared to Ishikawa cells alone. Low-grade cancer-associated stromal cells did not significantly influence hormone-regulated tumor growth. Addition of P4 attenuated tumor growth in Ishikawa + benign or high-grade stromal cells, but not in Ishikawa cells alone or with low-grade stromal cells. Using an angiogenesis focused real-time array TGFA, TGFB2 and TGFBR1 and VEGFC were identified as potential candidates for hormone-influenced growth regulation of tumors in the presence of benign and high-grade stromal cells. In summary, endometrial-cancer-associated cells responded differently to in vitro hormone treatment compared to benign endometrial stromal cells. Additionally, presence of stromal cells differentially influenced hormone-driven xenograft growth in vivo depending on the disease status of the stromal cells. PMID:25976290

  15. General Information About Endometrial Cancer

    MedlinePlus

    ... Research Endometrial Cancer Treatment (PDQ®)–Patient Version General Information About Endometrial Cancer Go to Health Professional Version ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  16. Dialogue and Adult Learning.

    ERIC Educational Resources Information Center

    Tarule, Jill Mattuck

    1992-01-01

    Discussion of the role of language and dialogue in adult learning looks at dialogue as epistemology and at talk as learning. It is proposed that the challenge in teaching and retaining adult learners is to create dialogue-rich classrooms, including many external speech opportunities, small-group discussion, and group projects. (MSE)

  17. Creating Dialogue by Storytelling

    ERIC Educational Resources Information Center

    Passila, Anne; Oikarinen, Tuija; Kallio, Anne

    2013-01-01

    Purpose: The objective of this paper is to develop practice and theory from Augusto Boal's dialogue technique (Image Theatre) for organisational use. The paper aims to examine how the members in an organisation create dialogue together by using a dramaturgical storytelling framework where the dialogue emerges from storytelling facilitated by…

  18. Brivanib Alaninate in Treating Patients With Recurrent or Persistent Endometrial Cancer

    ClinicalTrials.gov

    2016-03-16

    Endometrial Adenocarcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Mixed Adenocarcinoma; Endometrial Mucinous Adenocarcinoma; Endometrial Serous Adenocarcinoma; Endometrial Squamous Cell Carcinoma; Endometrial Transitional Cell Carcinoma; Endometrial Undifferentiated Carcinoma; Recurrent Uterine Corpus Carcinoma

  19. Probabilistic authenticated quantum dialogue

    NASA Astrophysics Data System (ADS)

    Hwang, Tzonelih; Luo, Yi-Ping

    2015-12-01

    This work proposes a probabilistic authenticated quantum dialogue (PAQD) based on Bell states with the following notable features. (1) In our proposed scheme, the dialogue is encoded in a probabilistic way, i.e., the same messages can be encoded into different quantum states, whereas in the state-of-the-art authenticated quantum dialogue (AQD), the dialogue is encoded in a deterministic way; (2) the pre-shared secret key between two communicants can be reused without any security loophole; (3) each dialogue in the proposed PAQD can be exchanged within only one-step quantum communication and one-step classical communication. However, in the state-of-the-art AQD protocols, both communicants have to run a QKD protocol for each dialogue and each dialogue requires multiple quantum as well as classical communicational steps; (4) nevertheless, the proposed scheme can resist the man-in-the-middle attack, the modification attack, and even other well-known attacks.

  20. Clomiphene citrate down-regulates estrogen receptor-α through the ubiquitin-proteasome pathway in a human endometrial cancer cell line.

    PubMed

    Amita, Mitsuyoshi; Takahashi, Toshifumi; Igarashi, Hideki; Nagase, Satoru

    2016-06-15

    We examined how clomiphene citrate (CC) reduces estrogen receptor-α (ERα) in a human endometrial cancer cell line. Ishikawa human endometrial cancer cells were treated with ERα ligands such as 17β-estradiol (E2), CC, and the pure antiestrogen, ICI 182,780 (ICI). Thereafter, the expression levels of ERα protein and mRNA were analyzed by western blot and real-time quantitative PCR, respectively, and those of ubiquitinated ERα were analyzed by immunoprecipitation of ERα followed by immunoblotting with an anti-ubiquitin antibody. The expression levels of ERα protein after treatment with E2, CC, and ICI were significantly decreased compared to pre-treatment levels without a corresponding decrease in ERα mRNA. These ligands significantly increased the levels of ubiquitinated ERα compared to vehicle treatment. Co-treatment with the proteasome inhibitor, MG132, abrogated the decrease in ERα levels caused by treatment with the ligands only. We demonstrated, for the first time, a CC-induced decrease in ERα mediated by the ubiquitin-proteasome pathway in human endometrial cancer cells. PMID:27033325

  1. Endometrial regeneration and endometrial stem/progenitor cells.

    PubMed

    Gargett, Caroline E; Nguyen, Hong P T; Ye, Louie

    2012-12-01

    The functional layer of the human endometrium is a highly regenerative tissue undergoing monthly cycles of growth, differentiation and shedding during a woman's reproductive years. Fluctuating levels of circulating estrogen and progesterone orchestrate this dramatic remodeling of human endometrium. The thin inactive endometrium of postmenopausal women which resembles the permanent basal layer of cycling endometrium retains the capacity to respond to exogenous sex steroid hormones to regenerate into a thick functional endometrium capable of supporting pregnancy. Endometrial regeneration also follows parturition and endometrial resection. In non menstruating rodents, endometrial epithelium undergoes rounds of proliferation and apoptosis during estrus cycles. The recent identification of adult stem cells in both human and mouse endometrium suggests that epithelial progenitor cells and the mesenchymal stem/stromal cells have key roles in the cyclical regeneration of endometrial epithelium and stroma. This review will summarize the evidence for endometrial stem/progenitor cells, examine their role in mouse models of endometrial epithelial repair and estrogen-induced endometrial regeneration, and also describe the generation of endometrial-like epithelium from human embryonic stem cells. With markers now available for identifying endometrial mesenchymal stem/stromal cells, their possible role in gynecological diseases associated with abnormal endometrial proliferation and their potential application in cell-based therapies to regenerate reproductive and other tissues will be discussed. PMID:22847235

  2. Inverse Relationship between Progesterone Receptor and Myc in Endometrial Cancer

    PubMed Central

    Dai, Donghai; Meng, Xiangbing; Thiel, Kristina W.; Leslie, Kimberly K.; Yang, Shujie

    2016-01-01

    Endometrial cancer, the most common gynecologic malignancy, is a hormonally-regulated disease. Response to progestin therapy positively correlates with hormone receptor expression, in particular progesterone receptor (PR). However, many advanced tumors lose PR expression. We recently reported that the efficacy of progestin therapy can be significantly enhanced by combining progestin with epigenetic modulators, which we term “molecularly enhanced progestin therapy.” What remained unclear was the mechanism of action and if estrogen receptor α (ERα), the principle inducer of PR, is necessary to restore functional expression of PR via molecularly enhanced progestin therapy. Therefore, we modeled advanced endometrial tumors that have lost both ERα and PR expression by generating ERα-null endometrial cancer cell lines. CRISPR-Cas9 technology was used to delete ERα at the genomic level. Our data demonstrate that treatment with a histone deacetylase inhibitor (HDACi) was sufficient to restore functional PR expression, even in cells devoid of ERα. Our studies also revealed that HDACi treatment results in marked downregulation of the oncogene Myc. We established that PR is a negative transcriptional regulator of Myc in endometrial cancer in the presence or absence of ERα, which is in contrast to studies in breast cancer cells. First, estrogen stimulation augmented PR expression and decreased Myc in endometrial cancer cell lines. Second, progesterone increased PR activity yet blunted Myc mRNA and protein expression. Finally, overexpression of PR by adenoviral transduction in ERα-null endometrial cancer cells significantly decreased expression of Myc and Myc-regulated genes. Analysis of the Cancer Genome Atlas (TCGA) database of endometrial tumors identified an inverse correlation between PR and Myc mRNA levels, with a corresponding inverse correlation between PR and Myc downstream transcriptional targets SRD5A1, CDK2 and CCNB1. Together, these data reveal a

  3. Cancer Statistics: Endometrial Cancer

    MedlinePlus

    ... at a Glance Show More At a Glance Estimated New Cases in 2016 60,050 % of All New Cancer Cases 3.6% Estimated Deaths in 2016 10,470 % of All Cancer ... of This Cancer : In 2013, there were an estimated 635,437 women living with endometrial cancer in ...

  4. Revisiting Dialogues and Monologues

    ERIC Educational Resources Information Center

    Kvernbekk, Tone

    2012-01-01

    In educational discourse dialogue tends to be viewed as being (morally) superior to monologue. When we look at them as basic forms of communication, we find that dialogue is a two-way, one-to-one form and monologue is a one-way, one-to-many form. In this paper I revisit the alleged (moral) superiority of dialogue. First, I problematize certain…

  5. Brain metastases from endometrial carcinoma.

    PubMed

    Piura, Ettie; Piura, Benjamin

    2012-01-01

    This paper will focus on knowledge related to brain metastases from endometrial carcinoma. To date, 115 cases were documented in the literature with an incidence of 0.6% among endometrial carcinoma patients. The endometrial carcinoma was usually an advanced-stage and high-grade tumor. In most patients (~90%), brain metastasis was detected after diagnosis of endometrial carcinoma with a median interval from diagnosis of endometrial carcinoma to diagnosis of brain metastases of 17 months. Brain metastasis from endometrial carcinoma was either an isolated disease limited to the brain only (~50%) or part of a disseminated disease involving also other parts of the body (~50%). Most often, brain metastasis from endometrial carcinoma affected the cerebrum (~75%) and was solitary (~60%). The median survival after diagnosis of brain metastases from endometrial carcinoma was 5 months; however, a significantly better survival was achieved with multimodal therapy including surgical resection or stereotactic radiosurgery followed by whole brain radiotherapy (WBRT) and/or chemotherapy compared to WBRT alone. It is suggested that brain imaging studies should be considered in the routine follow up of patients with endometrial carcinoma and that the search for a primary source in females with brain metastases of unknown primary should include endometrial biopsy. PMID:22523707

  6. Cancer of the Uterus (Endometrial Cancer)

    MedlinePlus

    ... Management Education & Events Advocacy For Patients About ACOG Cancer of the Uterus [Endometrial Cancer] Home For Patients Search FAQs Cancer of the ... Uterus [Endometrial Cancer] FAQ097, May 2011 PDF Format Cancer of the Uterus [Endometrial Cancer] Gynecologic Problems What ...

  7. Radiation Therapy With or Without Cisplatin in Treating Patients With Recurrent Endometrial Cancer

    ClinicalTrials.gov

    2016-02-09

    Endometrial Adenocarcinoma; Endometrial Adenosquamous Carcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Endometrioid Adenocarcinoma, Variant With Squamous Differentiation; Endometrial Serous Adenocarcinoma; Recurrent Uterine Corpus Carcinoma

  8. Hsa-microRNA-181a is a regulator of a number of cancer genes and a biomarker for endometrial carcinoma in patients: a bioinformatic and clinical study and the therapeutic implication

    PubMed Central

    He, Shuming; Zeng, Shumei; Zhou, Zhi-Wei; He, Zhi-Xu; Zhou, Shu-Feng

    2015-01-01

    The aberrant expression of human microRNA-181a-1 (hsa-miR-181a) has been implicated in the pathogenesis of various cancers, serving as an oncogene or a tumor suppressor. However, the role of hsa-miR-181a in the pathogenesis of endometrial carcinoma (EC) and its clinical significance are unclear. This study aimed to search for the molecular targets of hsa-miR-181a using bioinformatic tools and then determine the expression levels of hsa-miR-181a in normal, hyperplasia, and EC samples from humans. To predict the targets of hsa-miR-181a, ten different algorithms were used, including miRanda-mirSVR, DIANA microT v5.0, miRDB, RNA22 v2, TargetMiner, TargetScan 6.2, PicTar, MicroCosm Targets v5, and miRWALK. Two algorithms, TarBase 6.0 and miRTarBase, were used to identify the validated targets of hsa-miR-181a-5p (a mature product of hsa-miR-181a), and the web-based Database for Annotation, Visualization and Integrated Discovery (DAVID) 6.7 was used to provide biological functional interpretation of the validated targets of hsa-miR-181a-5p. A total of 78 formalin-fixed, paraffin-embedded tissue specimens from 65 patients and 13 healthy subjects were collected and examined, including normal endometrium (n=13), endometrial hyperplasia (n=18), and EC (37 type I and 10 type II EC cases). Our bioinformatic studies have showed that hsa-miR-181a might regulate a large number of target genes that are important in the regulation of critical cell processes, such as cell fate, cell survival, metabolism, and cell death. To date, 313 targets of hsa-miR-181a have been validated, and 22 of these targets are cancer genes. The precision of predictions by all the algorithms for hsa-miR-181a-1’s targets was low. Many of these genes are involved in tumorigenesis of various cancers, including EC, based on the DAVID and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. In comparison with normal endometrial tissue, the expression level of hsa-miR-181a was significantly

  9. Endometrial stem/progenitor cells: the first 10 years

    PubMed Central

    Gargett, Caroline E.; Schwab, Kjiana E.; Deane, James A.

    2016-01-01

    's syndrome. Endometrial MSCs (eMSCs) and menstrual blood stromal fibroblasts are an attractive source of MSCs for regenerative medicine because of their relative ease of acquisition with minimal morbidity. Their homologous and non-homologous use as autologous and allogeneic cells for therapeutic purposes is currently being assessed in preclinical animal models of pelvic organ prolapse and phase I/II clinical trials for cardiac failure. eMSCs and stromal fibroblasts also exhibit non-stem cell-associated immunomodulatory and anti-inflammatory properties, further emphasizing their desirable properties for cell-based therapies. CONCLUSIONS Much has been learnt about endometrial stem/progenitor cells in the 10 years since their discovery, although several unresolved issues remain. These include rationalizing the terminology and diagnostic characteristics used for distinguishing perivascular stem/progenitor cells from stromal fibroblasts, which also have considerable differentiation potential. The hierarchical relationship between clonogenic epithelial progenitor cells, endometrial and decidual SP cells, CD146+PDGFR-β+ and SUSD2+ cells and menstrual blood stromal fibroblasts still needs to be resolved. Developing more genetic animal models for investigating the role of endometrial stem/progenitor cells in endometrial disorders is required, as well as elucidating which bone marrow cells contribute to endometrial tissue. Deep sequencing and epigenetic profiling of enriched populations of endometrial stem/progenitor cells and their differentiated progeny at the population and single-cell level will shed new light on the regulation and function of endometrial stem/progenitor cells. PMID:26552890

  10. Persuasion Dialogues in ELT.

    ERIC Educational Resources Information Center

    Rutherford, Ramsey; Winks, Martin

    1978-01-01

    Some features of "persuasion dialogue" are examined, and suggestions are offered for ways in which persuasion might be used as a topic in the language class to stimulate the use of realistic language through appropriate role playing. Three dialogues are presented that illustrate different kinds of persuasion. (SW)

  11. Humanising Coursebook Dialogues

    ERIC Educational Resources Information Center

    Timmis, Ivor

    2016-01-01

    In this article, I argue that the most important thing about coursebook dialogues is not whether they are "authentic" or "inauthentic" but whether they are "plausible" as human interaction and behaviour. Coursebook dialogues are often constructed as vehicles for various kinds of language work and even sometimes as…

  12. Education as Dialogue

    ERIC Educational Resources Information Center

    Kazepides, Tasos

    2012-01-01

    The purpose of this paper is to show that genuine dialogue is a refined human achievement and probably the most valid criterion on the basis of which we can evaluate educational or social policy and practice. The paper explores the prerequisites of dialogue in the language games, the common certainties, the rules of logic and the variety of common…

  13. Endometrial carcinoma stage I.

    PubMed

    Baram, A; Ron, I; Kupferminc, M; Inbar, M

    1997-01-01

    Standard staging and therapeutic approach to endometrial cancer involves lymph node sampling (LNS) at the time of total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO). Lymphadenectomy prolongs time of surgery and increases the risk of morbidity; where other predictors are available, it may not contribute important supplementary information. 185/247 women with stage I endometrial carcinoma underwent the standard surgery while 62 underwent TAH+BSO. Recurrence and survival were monitored for a mean of 6.5 years and retrospectively reviewed: the rates for groups with and without known lymph node status were alike [13.5% (25/185) recurrence for the former and 12.9% (8/62) for the latter, and 5-year survival rates of 75.7% (140/185) for the former and 74.2 (46/62) for the latter]. Myometrial invasion and histological grade appeared to have been highly accurate predictors without lymph node information. Because information on histological grade is available early and is highly predictive, its use could be incorporated into a revised management algorithm for stage I endometrial cancer which would depend upon ensuring lymphadenectomy for women with low grade histopathology and omitting it for those with high grades on the grounds that no further information is necessary to act appropriately. PMID:21590195

  14. microRNAs and Endometrial Pathophysiology.

    PubMed

    Chill, Henry H; Dior, Uri P; Kogan, Liron; Revel, Ariel

    2015-01-01

    Embryo implantation requires a reciprocal interaction between the blastocyst and endometrium and is associated with complex regulatory mechanisms. Since their discovery, microRNAs became prominent candidates providing missing links for many biological pathways. In recent years, microRNAs were implicated as one of the important players in regulation of various biological and physiological endometrial related processes. This chapter aims to present recent knowledge pertaining to the diverse aspects of microRNAs in the embryo-endometrial relationship. We will focus on the role of microRNAs in decidualization and their part in natural and stimulated cycles. Next, we will present recent studies deliberating the role of microRNAs in recurrent pregnancy loss and in the important phenomenon of recurrent implantation failure. Lastly, demonstrating an important aspect of embryo implantation and invasion, we will outline few microRNA related shared pathways of implantation and carcinogenesis. PMID:26662990

  15. The Significance of miR-34a Expression in Endometrial Carcinogenesis: Correlation With Expression of p16 and Ki-67 Proteins in Endometrial Cancers

    PubMed Central

    Choi, Yoon Sung; Lee, Kyung Eun

    2015-01-01

    Background: A microRNA, miR-34a, plays a key role in inhibiting cellular transformation and carcinogenesis by controlling cell cycle regulation and cell proliferation in various human tumors. However, miR-34a has rarely been reported in endometrial cancer research in Korea. This study was undertaken to analyze miR-34a expression in simple endometrial hyperplasia and endometrial cancer, and to evaluate the relationship between expression of miR-34a and p16 and Ki-67 proteins in endometrial cancers. Methods: A retrospective study was carried out on 66 formalin-fixed, paraffin-embedded tissues with simple endometrial hyperplasia (31 cases) and endometrial cancer (35 cases) patients. These were analyzed for miR-34a expression by quantitative real-time PCR, and the expression of p16 and Ki-67 proteins in endometrial cancers was evaluated by immunohistochemistry. Results: The miR-34a expression level was lower in endometrial cancer tissues (−0.71 ± 3.90) than in simple endometrial hyperplasia tissues (2.68 ± 8.62). The endometrial hyperplasia tissues showed underexpression of miR-34a in 13 of the 31 cases (41.9%) while the endometrial cancer tissues showed underexpression of miR-34a in 24 of 35 cases (68.6%). Thus, miR-34a was significantly underexpressed in endometrial cancer tissues when compared endometrial hyperplasia tissues (P = 0.046). Overexpression of p16 was detected in 25 (71.4%) and Ki-67 immunoreactivity was detected in 27 (77.1%) of the 35 endometrial cancers. Although not statistically significant, the frequency of p16 and Ki-67 overexpression tended to be lower in the cases with miR-34a underexpression than in cases with miR-34a overexpression. Conclusions: These findings suggest that underexpression of miR-34a might be involved in endometrial carcinogenesis. Further studies are needed to define the relationship between miR-34a expression and tissue specific protein expression. PMID:26734589

  16. A Trial for Patients With Advanced/Recurrent Endometrial Cancer

    ClinicalTrials.gov

    2009-11-13

    Neoplasms; Neoplasms by Site; Urogenital Neoplasms; Genital Neoplasms, Female; Uterine Neoplasms; Endometrial Neoplasms; Cancer of Endometrium; Endometrial Cancer; Cancer of the Endometrium; Endometrium Cancer; Neoplasms, Endometrial

  17. Inflammation and endometrial bleeding.

    PubMed

    Berbic, M; Ng, C H M; Fraser, I S

    2014-12-01

    Most of the key physiological processes in the human reproductive tract involve a significant inflammatory component. These processes include follicle development, ovulation, implantation, pregnancy, labor, postpartum, remodeling and menstruation. In this context, the term 'inflammation' usually means an influx of leukocytes ('immune cells'), often of different types, into a reproductive tract tissue. These examples of inflammation are not overtly associated with any infective process. There may also be evidence that these invading leukocytes have altered their functions to take on specific and relevant local regulatory roles. Specific sequential changes in different leukocytes can be demonstrated within human endometrium during the different phases of the normal menstrual cycle. Leukocytes are fairly sparse in numbers through the proliferative phase, but increase substantially into and through the secretory phase, so much so that around 40% of all stromal cells in the premenstrual phase are leukocytes, mainly uterine natural killer cells, a large granulated lymphocyte. Other leukocytes which play key roles in menstruation appear to be macrophages, mast cells, dendritic cells, neutrophils, eosinophils and regulatory T cells. Premenstrual withdrawal of progesterone increases the endometrial expression of inflammatory mediators, including IL-8 and MCP-1, which are believed to drive endometrial leukocyte recruitment at this time. Macrophages and neutrophils are rich sources of defensins and whey acid protein motif proteins, which play important roles in ensuring microbial protection while the epithelial barrier is disrupted. Mast cells are increasingly activated as the menstrual phase approaches, and leukocyte proteases trigger a cascade of matrix metalloproteinases and degradation of extracellular matrix. Dendritic cells and other antigen-presenting cells (e.g. macrophages) almost certainly facilitate clearance of cellular debris from the uterine cavity, and reduce

  18. Metabolic vulnerabilities in endometrial cancer.

    PubMed

    Byrne, Frances L; Poon, Ivan K H; Modesitt, Susan C; Tomsig, Jose L; Chow, Jenny D Y; Healy, Marin E; Baker, William D; Atkins, Kristen A; Lancaster, Johnathan M; Marchion, Douglas C; Moley, Kelle H; Ravichandran, Kodi S; Slack-Davis, Jill K; Hoehn, Kyle L

    2014-10-15

    Women with metabolic disorders, including obesity and diabetes, have an increased risk of developing endometrial cancer. However, the metabolism of endometrial tumors themselves has been largely understudied. Comparing human endometrial tumors and cells with their nonmalignant counterparts, we found that upregulation of the glucose transporter GLUT6 was more closely associated with the cancer phenotype than other hallmark cancer genes, including hexokinase 2 and pyruvate kinase M2. Importantly, suppression of GLUT6 expression inhibited glycolysis and survival of endometrial cancer cells. Glycolysis and lipogenesis were also highly coupled with the cancer phenotype in patient samples and cells. To test whether targeting endometrial cancer metabolism could be exploited as a therapeutic strategy, we screened a panel of compounds known to target diverse metabolic pathways in endometrial cells. We identified that the glycolytic inhibitor, 3-bromopyruvate, is a powerful antagonist of lipogenesis through pyruvylation of CoA. We also provide evidence that 3-bromopyruvate promotes cell death via a necrotic mechanism that does not involve reactive oxygen species and that 3-bromopyruvate impaired the growth of endometrial cancer xenografts. PMID:25205105

  19. What Are the Key Statistics about Endometrial Cancer?

    MedlinePlus

    ... cancer? Next Topic Endometrial cancer risk factors Key statistics for endometrial cancer? How common is endometrial cancer? ... endometrial cancer. Visit the American Cancer Society’s Cancer Statistics Center for more key statistics. Last Medical Review: ...

  20. Mutant p53 (p53-R248Q) functions as an oncogene in promoting endometrial cancer by up-regulating REGγ.

    PubMed

    Wang, Huihui; Bao, Wei; Jiang, Feizhou; Che, Qi; Chen, Zheng; Wang, Fangyuan; Tong, Huan; Dai, Chenyun; He, Xiaoying; Liao, Yun; Liu, Binya; Sun, Jing; Wan, Xiaoping

    2015-05-01

    P53 mutation plays a pivotal role in tumorigenesis of endometrial cancer (EC), here we report that the gain-of-function mutant p53-R248Q targets the proteasome activator REGγ to promote EC progression. Increased p53 expression significantly correlated with high pathological grade and lymph node metastasis in EC specimens. Manipulation of p53-R248Q in EC cells caused coincident changes in REGγ expression, and chromatin immunoprecipitation coupled with PCR further indicated that p53-R248Q bound to the REGγ gene promoter at a p53 responsive element. Silencing of REGγ in EC cells attenuated the cell proliferation, migration and invasion abilities, whereas overexpression of p53-R248Q rescued these activities. Overexpression of REGγ also induced an epithelial-mesenchymal transition phenotype. Moreover, a mouse xenograft tumor model showed that REGγ promoted tumor growth, further demonstrating a p53-R248Q-REGγ oncogenic pathway. Finally, examination of EC and normal endometrium specimens confirmed the oncogenic role of REGγ, in that REGγ was more highly overexpressed in p53-positive specimens than in p53-negative specimens. Our data suggest that REGγ is a promising therapeutic target for EC with the p53-R248Q mutation. PMID:25697482

  1. Drugs Approved for Endometrial Cancer

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for endometrial cancer. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  2. Let7a inhibits the growth of endometrial carcinoma cells by targeting Aurora-B.

    PubMed

    Liu, Ping; Qi, Meiyan; Ma, Chengbin; Lao, Guoying; Liu, Yu; Liu, Yan; Liu, Yingzi

    2013-08-19

    MicroRNAs negatively regulate target gene expression at the post-transcriptional level during carcinogenesis. Recent advances revealed that the expression levels of several miRNAs are up- or down-regulated in endometrial carcinoma (EC). Here we identify dysregulated miRNAs in EC and we elucidate the essential role of let-7a. The expression of 86 miRNAs in EC was found to be different from adjacent normal endometrial tissues. Moreover, miR-let-7 members are down-regulated in EC and let-7 miRNAs are highly associated with endometrial cancer. A functional investigation revealed that let-7a suppressed proliferation of HeLa cells by targeting Aurora-B. Let-7a also antagonizes Aurora-B functions in promoting carcinoma cell proliferation by down-regulating Aurora-B protein level. Let-7a could be applied for gene therapy against endometrial carcinogenesis. PMID:23769985

  3. Comparison of Two Combination Chemotherapy Regimens Plus Radiation Therapy in Treating Patients With Stage III or Stage IV Endometrial Cancer

    ClinicalTrials.gov

    2015-04-30

    Endometrial Adenocarcinoma; Endometrial Adenosquamous Carcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Endometrioid Adenocarcinoma, Variant With Squamous Differentiation; Endometrial Serous Adenocarcinoma; Stage III Uterine Corpus Cancer

  4. CXCL12/CXCR4 axis induces proliferation and invasion in human endometrial cancer

    PubMed Central

    Liu, Pingping; Long, Ping; Huang, Yu; Sun, Fengyi; Wang, Zhenyan

    2016-01-01

    Objective: Since that we have previously found CXCL12/CXCR4, an important biological axis is highly transcribed in several cancer cells. We aim to investigate whether CXCL12/CXCR4 axis regulates critical processes in neoplastic transformation that affects endometrial cancer cell biology. Methods: The expression levels of CXCR4 were analyzed in human normal endometrial tissue, simple hyperplasia, atypical hyperplasia and endometrial cancer cells by immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR). Serum CXCL12 was measured by Enzyme-Linked Immunosorbent Assay (ELISA) in Ishikawa endometrial cancer cell line. To study the biological function of CXCL12/CXCR4 in endometrial cancer, short interfering RNA silencing of CXCR4 was established to analyze the roles of CXCL12/CXCR4 in proliferation, migration, invasion and apoptosis of Ishikawa cells in vitro. Results: The expression level of CXCR4 in endometrial cancer tissue was higher as compared to atypical hyperplasia, simple hyperplasia and normal cycling endometrium cells. Ishikawa cells secreted CXCL12 spontaneously and continuously for 96 hrs in culture. The proliferation, migration and invasion of Ishikawa cells was significantly induced, and the apoptosis was significantly reduced by CXCL12 in combination with CXCR4. Moreover, CXCR4 silencing could significantly antagonize all these functions. Conclusions: CXCL12/CXCR4 axis plays an important role in the proliferation, invasion and metastasis of endometrial cancer, indicating that CXCR4 could be the target for the treatment of endometrial cancer. PMID:27186295

  5. Estrogens and endometrial carcinoma.

    PubMed

    Gray, L A; Christopherson, W M; Hoover, R N

    1977-04-01

    A group of 205 women with endometrial carcinoma was matched for age, parity, and year of operation with a group of 205 women who had had hysterectomies for benign disease. In the former group, 32 patients had used conjugated estrogens, while in the latter group 12 had used this hormone, yielding a relative risk of 3.1 (P = 0.0008). Users of other forms of systemic estrogens showed similar elevations in relative risk. Relative risk was related to duration of use, progressing from no evidence of risk among those using the hormone for less than 5 years to an 11.5-fold greater risk for those using it for 10 years or more. Risk was also related to the strength of the medication. The relative risk for users of the 1.25-mg tablets was 12.7 as compared to a two- to fourfold greater risk among users of lesser strength tablets. PMID:193072

  6. Imaging in endometrial carcinoma

    PubMed Central

    Faria, Silvana C; Sagebiel, Tara; Balachandran, Aparna; Devine, Catherine; Lal, Chandana; Bhosale, Priya R

    2015-01-01

    Endometrial carcinoma (EC) is the most common gynecologic malignancy in the United States. Prognosis depends on patient age, histological grade, depth of myometrial invasion and/or cervical invasion, and the presence of lymph node metastases. Although EC is staged surgically according to the International Federation of Gynecology and Obstetrics (FIGO) system, preoperative imaging can assist in optimal treatment planning. Several imaging techniques such as transvaginal ultrasonography (TVUS), computed tomography (CT), and magnetic resonance imaging (MRI) have been used as diagnostic tools for preoperative staging of EC. Recently, positron emission tomography (PET), PET/CT, and PET/MRI have also been used in staging these patients. In this article, we review the value of imaging in diagnosis, staging, treatment planning, and detection of recurrent disease in patients with EC. PMID:25969637

  7. Signalling pathways in endometrial cancer.

    PubMed

    Markowska, Anna; Pawałowska, Monika; Lubin, Jolanta; Markowska, Janina

    2014-01-01

    Carcinogenesis is a multistage process, during which the activity of signalling pathways responsible for cell cycle regulation and division is disrupted which leads to inhibition of apoptosis and enhanced proliferation. Improper activation of Wnt/β-catenin and PI3K. Akt pathways play essential role in endometrial cancers (EC), mainly type I. Mutations in APC, axin or CTNBB1 may lead to β-catenin overactivation leading to excessive gene expression. PTEN inactivation, mutations in the PIK3CA or Akt result in increased transmission in the PI3K/Akt pathway, apoptosis inhibition, intensive cell division, mTOR excitation. In non-endometrioid cancers, key mutations include suppressor gene TP53 responsible for repairing damaged DNA or apoptosis initiation. Irregularities in gene P16, encoding a protein forming the p16-cyclinD/CDK-pRb have also been described. Understanding the complex relations between specific proteins taking part in signal transduction of the abovementioned pathways is key to research on drugs used in targeted therapy. PMID:25520571

  8. Empowering Dialogues in Humanistic Education

    ERIC Educational Resources Information Center

    Aloni, Nimrod

    2013-01-01

    In this article I propose a conception of empowering educational dialogue within the framework of humanistic education. It is based on the notions of Humanistic Education and Empowerment, and draws on a large and diverse repertoire of dialogues--from the classical Socratic, Confucian and Talmudic dialogues, to the modern ones associated with the…

  9. Learning to Internalize Action Dialogue

    ERIC Educational Resources Information Center

    Cotter, Teresa Ellen

    2011-01-01

    The purpose of this case study was to explore how participants of a communications workshop, "Action Dialogue," perceived their ability to engage in dialogue was improved and enhanced. The study was based on the following assumptions: (1) dialogue skills can be learned and people are able to learn these skills; (2) context and emotion influence…

  10. The Paradox of Dialogue

    ERIC Educational Resources Information Center

    Murphy, Peter

    2011-01-01

    The Council of Europe's 2008 "White Paper on Intercultural Dialogue" signalled--with a measure of deep concern--the limits of multiculturalism and its attendant problems of identity politics, communal segregation, and the undermining of rights and freedoms in culturally closed communities. The White Paper proposed the replacement of the policy of…

  11. Learning through Ethnographic Dialogues

    ERIC Educational Resources Information Center

    Landis, David; Kalieva, Rysaldy; Abitova, Sanim; Izmukhanbetova, Sophia; Musaeva, Zhanbota

    2006-01-01

    This article describes ways that conversations constituted ethnographic research for students and teachers in Kazakhstan. Through dialogues with local community members, students worked as researchers to develop knowledge about cultural patterns and social life. Ethnographic research and writing provided valuable language and research experiences…

  12. Russian Supplementary Dialogues.

    ERIC Educational Resources Information Center

    Peace Corps, Ashgabat (Turkmenistan).

    This manual is designed for the Russian language training of Peace Corps volunteers serving in Turkmenistan, and focuses on daily communication skills needed in that context. It consists of nine topical lessons, each containing several brief dialogues targeting specific language competencies, and exercises. Text is entirely in Russian, except for…

  13. Capabilities for Intercultural Dialogue

    ERIC Educational Resources Information Center

    Crosbie, Veronica

    2014-01-01

    The capabilities approach offers a valuable analytical lens for exploring the challenge and complexity of intercultural dialogue in contemporary settings. The central tenets of the approach, developed by Amartya Sen and Martha Nussbaum, involve a set of humanistic goals including the recognition that development is a process whereby people's…

  14. Education as Dialogue

    ERIC Educational Resources Information Center

    Jourard, Sidney M.

    1978-01-01

    In this discussion, the author's last public presentation before his death in 1974, is a dedication to dialogue as the essence of education. In the midst of modern consciousness-altering technology, he valued authentic conservation more powerful than LSD, meditation, and all the rest. (Editor/RK)

  15. Photodynamic therapy toward selective endometrial ablation

    NASA Astrophysics Data System (ADS)

    Tadir, Yona; Tromberg, Bruce J.; Krasieva, Tatiana B.; Berns, Michael W.

    1993-05-01

    Potential applications of photodynamic therapy for endometrial disease are discussed. Experimental models that may lead to diagnosis and treatment of endometriosis as well as selective endometrial ablation are summarized.

  16. Can Endometrial Cancer Be Found Early?

    MedlinePlus

    ... Next Topic Signs and symptoms of endometrial cancer Can endometrial cancer be found early? In most cases, ... reach an advanced stage before signs and symptoms can be noticed. More information can be found in “ ...

  17. Aberrant expression of hSef and Sprouty4 in endometrial adenocarcinoma

    PubMed Central

    ZHANG, HUI; GUO, QIUFEN; WANG, XIA; WANG, CHONG; ZHAO, XINGBO; LI, MINGJIANG

    2016-01-01

    Fibroblast growth factor (FGF) 2-mediated signaling of the mitogen-activated protein kinase/RAS/extracellular signal-regulated kinase 1/2 pathway is a critical modulator in angiogenesis and is therefore essential for the pathogenesis of endometrial carcinoma. Human similar expression to FGFs (hSef) and Sprouty4 have each been reported to be negative regulators of FGF signaling. The aim of the present study was to investigate the expression of hSef and Sprouty4 in human endometrial adenocarcinoma. Using immunohistochemistry analysis, the expression of hSef and Sprouty4 was detected in human endometrial adenocarcinomas. Increased hSef expression was found to be present in endometrial adenocarcinomas. In addition, decreased hSef expression was identified in the blood vessels of endometrial adenocarcinoma samples. However, the expression of Sprouty4 was downregulated in human endometrial adenocarcinoma. Aberrant expression of hSef and Sprouty4 are involved in the pathogenesis of human endometrial adenocarcinoma. PMID:26870165

  18. Intensity-Modulated Radiation Therapy, Cisplatin, and Bevacizumab Followed by Carboplatin and Paclitaxel in Treating Patients Who Have Undergone Surgery for Endometrial Cancer

    ClinicalTrials.gov

    2014-10-09

    Endometrial Adenocarcinoma; Endometrial Adenosquamous Cell Carcinoma; Endometrial Clear Cell Carcinoma; Endometrial Papillary Serous Carcinoma; Stage I Endometrial Carcinoma; Stage II Endometrial Carcinoma; Stage III Endometrial Carcinoma; Stage IV Endometrial Carcinoma

  19. Adjuvant therapy for endometrial cancer

    PubMed Central

    DeLeon, Maria C.; Ammakkanavar, Natraj R.

    2014-01-01

    Endometrial cancer is a common gynecologic malignancy typically diagnosed at early stage and cured with surgery alone. Adjuvant therapy is tailored according to the risk of recurrence, estimated based on the International Federation of Gynecology and Obstetrics (FIGO) stage and other histological factors. The objective of this manuscript is to review the evidence guiding adjuvant therapy for early stage and locally advanced uterine cancer. For patients with early stage disease, minimizing toxicity, while preserving outstanding cure rates remains the major goal. For patients with locally advanced endometrial cancer optimal combined regimens are being defined. Risk stratification based on molecular traits is under development and may aid refine the current risk prediction model and permit personalized approaches for women with endometrial cancer. PMID:24761218

  20. Equine Endometrial Gland Density and Endometrial Thickness Vary among Sampling Sites in Thoroughbred Mares

    PubMed Central

    HANADA, Michiko; MAEDA, Yousuke; OIKAWA, Masa-aki

    2012-01-01

    The secretions of the equine endometrial glands are essential for the survival, growth, and development of the conceptus in early pregnancy, and endometrial gland density is directly related to successful pregnancy outcome. Endometrial biopsy is routinely used to assess the reproductive potential of broodmares. Some previous studies have shown that equine endometrial glands are uniformly distributed throughout the uterus; however, other work has shown variation of the endometrial architecture between biopsy sites, suggesting that a single biopsy is not representative of the entire endometrium. The aims of this study were to assess and compare the endometrial gland density and thickness at four sampling sites in the uterus (the central segment of each uterine horn, the uterine horn-body junction, and the caudal portion of the uterine body). Endometrial samples from five nulliparous Thoroughbred mares in diestrus were obtained at necropsy and used for subsequent histomorphometric analysis. The caudal uterine body had a significantly lower endometrial gland density and endometrial thickness than the other sites. This may result in nutrient deprivation and reduced survival of embryos or fetuses in this region of the uterus. The endometrial gland density and endometrial thickness did not significantly differ between the other regions sampled, indicating that they are similarly suitable for embryonic implantation and fetal development. Our results suggest that the endometrial structure of the caudal uterine body of the mare is not representative of the endometrial morphology at other sites. Thus, the caudal uterine body is not a suitable site for routine endometrial biopsy. PMID:24833993

  1. Role of MicroRNAs in carcinogenesis that potential for biomarker of endometrial cancer.

    PubMed

    Widodo; Djati, Muhammad Sasmito; Rifa'i, Muhaimin

    2016-05-01

    The non-invasive diagnostic tool for early detection of endometrial cancer still limited. The etiology of this disease is believed to be associated with disharmony hormone production. One predominant factor that regulate hormone production is microRNA (miRNAs). Some studies reported that miRNAs play a significant role in the process carcinogenesis. We have identified 12 of miRNAs that potentially have a role in controlling endometrial carcinogenesis pathways. Further analysis suggested that these miRNA targeted genes that regulate the early development of endometrial cancer. These genes cluster into several functional groups involving a process of angiogenesis, apoptosis, cell cycle, cell proliferation and p53 pathways. Some of the genes are PTEN, GSK3b, and TP53, which are a tumor suppressor that control the process of growth arrest, DNA Repair, and Apoptosis. Upregulation of the miRNA may obstruct the cell ability to control the cell cycle. This study was found three miRNA that plays a role in the development of endometrial cancer. The hsa-miR-495 and hsa-miR-152 were repressed in endometrial cancer compared to normal tissue. The microRNA regulate genes that control proliferation and cell survival. Moreover, hsa-miR-181d was upregulated to control expression a tumor suppressor gene, PTEN to protect the cancer cell from apoptosis. Further investigation to validate the function of the miRNA is a warrant for developing biomarkers of endometrial carcinoma. PMID:27006767

  2. Research on Spoken Dialogue Systems

    NASA Technical Reports Server (NTRS)

    Aist, Gregory; Hieronymus, James; Dowding, John; Hockey, Beth Ann; Rayner, Manny; Chatzichrisafis, Nikos; Farrell, Kim; Renders, Jean-Michel

    2010-01-01

    Research in the field of spoken dialogue systems has been performed with the goal of making such systems more robust and easier to use in demanding situations. The term "spoken dialogue systems" signifies unified software systems containing speech-recognition, speech-synthesis, dialogue management, and ancillary components that enable human users to communicate, using natural spoken language or nearly natural prescribed spoken language, with other software systems that provide information and/or services.

  3. The cancer marker neutrophil gelatinase-associated lipocalin is highly expressed in human endometrial hyperplasia.

    PubMed

    Liao, Chi-Jr; Huang, Yen Hua; Au, Heng-Kien; Wang, Le-Ming; Chu, Sin-Tak

    2012-02-01

    Recently, endometrial hyperplasia was identified as presenting a higher risk for progressing to endometrial carcinoma more readily than adenomyosis. The Lcn-2 gene encodes neutrophil gelatinase-associated lipocalin (NGAL), which promotes cell proliferation and serves as a cancer marker in some cancers. In our current study, we investigated the relationship between the expression of NGAL and that of pathogenic cytokines and cancer-related genes including cyclooxygenase-2 (COX-2), E-cadherin, β-catenin, and vimentin in patients with endometrial disorders. NGAL expression was examined by Western blotting, immunohistochemistry, and reverse-transcription polymerase chain reaction (RT-PCR) in hyperplasia and adenomyosis biopsy samples. Immunohistochemistry demonstrated the occurrence of NGAL in glandular epithelial cells but not in the stromal cells of hyperplasia biopsy samples. NGAL protein and mRNA expression were significantly greater in endometrial hyperplasia than in endometrial adenomyosis. Although our data showed no difference in pathogenic cytokines between patients with endometrial hyperplasia and endometrial adenomyosis, we observed high expression levels of COX-2, β-catenin, vimentin, and E-cadherin in patients with endometrial hyperplasia. NGAL mRNA expression correlated positively with COX-2 and E-cadherin mRNA expression (r = 0.41 and r = 0.57, respectively), but correlated negatively with vimentin and β-catenin mRNA expression (r = -0.42 and r = -0.61, respectively). Our data suggest that NGAL is up-regulated in patients with endometrial hyperplasia to prevent the transition from hyperplasia to carcinoma. PMID:21573795

  4. Silent images in dialogue

    NASA Astrophysics Data System (ADS)

    Azevedo, Isabel; Sandford-Richardson, Elizabeth; Richardson, Martin; Bernardo, Luis Miguel; Crespo, Helder

    2016-03-01

    In this series of digital art holograms and lenticulars, we used the HoloCam Portable Light System with the 35 mm cameras, Canon IS3 and the Canon 700D, to capture the image information, it was then edited on the computer using Motion 5 and Final Cut Pro X programs. We are presenting several actions in the digital holographic space. The figures are in dialogue within the holographic space and the viewer, in front of the holographic plate. In holography the time of the image is the time of the viewer present. And that particular feature is what distinguishes digital holography from other media.

  5. Participation of WNT and β-Catenin in Physiological and Pathological Endometrial Changes: Association with Angiogenesis

    PubMed Central

    Kiewisz, Jolanta; Wasniewski, Tomasz; Kmiec, Zbigniew

    2015-01-01

    WNT proteins are involved in embryonic development, sex determination, stem cell recruitment, angiogenesis, and cancer. They take part in morphological changes in the endometrium during development, regulate processes of endometrial proliferation and differentiation. This review presents current knowledge about implication of WNT proteins and β-catenin in physiological endometrial functions as well as their involvement in uterine carcinogenesis. Influence of WNT proteins on the formation of blood vessel, taking place both under healthy and pathological conditions, is also considered. Participation of WNT proteins, β-catenin, and inhibitors and inducers of WNT signaling in the process of endometrial angiogenesis is largely unknown. Thus, confirmation of their local and systemic participation in the process of endometrial angiogenesis may in the long term help to establish new diagnostic and therapeutic approaches in conditions associated with the pathology of the female reproductive system. PMID:26366420

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

    MedlinePlus

    ... Next Topic Additional resources for endometrial cancer What`s new in endometrial cancer research and treatment? Molecular pathology ... that caused the endometrial cells to become cancerous. New treatments New drugs, combinations of drugs and targeted ...

  7. 6 Common Cancers - Gynecologic Cancers Cervical, Endometrial, and Ovarian

    MedlinePlus

    ... Bar Home Current Issue Past Issues 6 Common Cancers - Gynecologic Cancers Cervical, Endometrial, and Ovarian Past Issues / Spring 2007 ... of this page please turn Javascript on. Gynecologic Cancers Cervical, Endometrial, and Ovarian NCI estimates that endometrial, ...

  8. Intracrine Androgens Enhance Decidualization and Modulate Expression of Human Endometrial Receptivity Genes

    PubMed Central

    Gibson, Douglas A.; Simitsidellis, Ioannis; Cousins, Fiona L.; Critchley, Hilary O. D.; Saunders, Philippa T. K.

    2016-01-01

    The endometrium is a complex, steroid-dependent tissue that undergoes dynamic cyclical remodelling. Transformation of stromal fibroblasts (ESC) into specialised secretory cells (decidualization) is fundamental to the establishment of a receptive endometrial microenvironment which can support and maintain pregnancy. Androgen receptors (AR) are present in ESC; in other tissues local metabolism of ovarian and adrenal-derived androgens regulate AR-dependent gene expression. We hypothesised that altered expression/activity of androgen biosynthetic enzymes would regulate tissue availability of bioactive androgens and the process of decidualization. Primary human ESC were treated in vitro for 1–8 days with progesterone and cAMP (decidualized) in the presence or absence of the AR antagonist flutamide. Time and treatment-dependent changes in genes essential for a) intra-tissue biosynthesis of androgens (5α-reductase/SRD5A1, aldo-keto reductase family 1 member C3/AKR1C3), b) establishment of endometrial decidualization (IGFBP1, prolactin) and c) endometrial receptivity (SPP1, MAOA, EDNRB) were measured. Decidualization of ESC resulted in significant time-dependent changes in expression of AKR1C3 and SRD5A1 and secretion of T/DHT. Addition of flutamide significantly reduced secretion of IGFBP1 and prolactin and altered the expression of endometrial receptivity markers. Intracrine biosynthesis of endometrial androgens during decidualization may play a key role in endometrial receptivity and offer a novel target for fertility treatment. PMID:26817618

  9. Influence of VEGFR and LHCGR on endometrial adenocarcinoma

    PubMed Central

    Kölbl, Alexandra C.; Birk, Amelie E.; Kuhn, Christina; Jeschke, Udo; Andergassen, Ulrich

    2016-01-01

    Endometrial adenocarcinoma is a common gynecological malignancy that is usually treated by surgical resection followed by radiation. However, the frequency of remote metastasis is high. The present study aimed to investigate whether patients with endometrial adenocarcinoma exhibited a positive response to treatment with a gonadotropin-releasing hormone analogue or inhibitors of neoangiogenesis, which are applied for the treatment of other malignancies. Immunohistochemical analyses were performed using 203 paraffin-embedded tissue samples of endometrial adenocarcinomas from patients who had undergone surgery at the Department of Obstetrics and Gynecology of the Ludwig Maximilians University of Munich, Germany. The tissues were incubated with antibodies against luteinizing hormone/choriogonadotropin receptor (LHCGR) and vascular endothelial growth factor receptor 2 (VEGFR2), and evaluated by bright field microscopy. The staining was categorized according to the Immune-Reactive-Score (IRS). The IRS scores were then statistically associated with various tumor traits, including tumor size, lymph node status, metastasis, grade, expression of steroid hormone receptors and patient survival. There was a significant association between VEGFR2 expression and tumor grading and estrogen receptor-α (ERα). For LHCGR, a correlation was observed with ERα and progesterone receptor (PR). No correlations were identified between VEGFR2 or LHCGR expression and the other examined tumor traits or patient survival. The associations between VEGFR2 and ERα, and between LHCGR and ERα or PR, may be explained by the interaction of these signal transduction molecules in the regulation of cellular growth and differentiation. These mechanisms also have an important role in the formation of remote metastases, which is the main cause for tumor-associated mortality. The results of the present study suggested that patients with endometrial adenocarcinoma may benefit from treatment with inhibitors

  10. John Dewey Lives: A Dialogue

    ERIC Educational Resources Information Center

    Ayers, William C.; Schubert, William H.

    2012-01-01

    This dialogue is an edited version of a dialogue between William C. Ayers and William H. Schubert at the November 10-12, 2011, meeting of the Progressive Education Network hosted by the Francis W. Parker School in Chicago, Illinois. It was the opening keynote session on the evening of November 10. Ayers interviewed Schubert, who acted as John…

  11. Jim and Dave: A Dialogue.

    ERIC Educational Resources Information Center

    Doud, Robert E.

    This is a fictional dialogue intended to honor Jim Kingman and David Leary, both professors of history who retired after long careers at Pasadena City College in California (PCC). The dialogue hypothesizes the observations of both men as they look on the honorary gold plates of previous retirees that decorate the wall of a PCC public dining hall.…

  12. Imre Lakatos's Use of Dialogue.

    ERIC Educational Resources Information Center

    Greig, Judith Maxwell

    This paper uses a book, "Proofs and Refutations: The Logic of Mathematical Discovery," as an example of Lakatos's use of dialogue. The book was originally adapted from his dissertation and influenced by Polya and Popper. His discussion of the Euler conjecture is summarized. Three purposes for choosing the dialogue form for the book were that it…

  13. Bone morphogenetic protein 2 (BMP2) and krüppel-like factor 9 (KLF9) cross-regulation in uterine stromal cells promotes timing of uterine endometrial receptivity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An out-of-phase uterus is considered to be a major cause of infertility in mammals. Delayed on-time implantation of developing blastocysts, due to asynchronous endometrial development, results in reduced litter size in mice. The dysregulation of events in the transition from a pre-receptive to a re...

  14. Adjuvant progestagens for endometrial cancer

    PubMed Central

    Martin-Hirsch, Pierre PL; Bryant, Andrew; Keep, Sarah L; Kitchener, Henry C; Lilford, Richard

    2014-01-01

    Background Endometrial cancer is the most common genital tract carcinoma among women in developed countries, with most women presenting with stage 1 disease. Adjuvant progestagen therapy has been advocated following primary surgery to reduce the risk of recurrence of disease. Objectives To evaluate the effectiveness and safety of adjuvant progestagen therapy for the treatment of endometrial cancer. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Specilaised Register, Cochrane Central Register of Controlled Trials (CENTRAL) Issue 2, 2009. MEDLINE and EMBASE up to April 2009. Selection criteria Randomised controlled trials (RCTs) of progestagen therapy in women who have had surgery for endometrial cancer. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Risk ratios (RRs) comparing survival in women who did and did not receive progestagen were pooled in random effects meta-analyses.. Main results Seven trials assessing 4556 women were identified. Three trials included women with stage one disease only, whereas four included women with more advanced disease. Meta-analysis of four trials showed that there was no significant difference in the risk of death at five years between adjuvant progestagen therapy and no further treatment (RR = 1.00, 95% CI 0.85 to 1.18). This conclusion is also robust to single trial analyses at 4 and 7 years and in one trial across all points in time using a hazard ratio (HR). There was also no significant difference between progestagen therapy and control in terms of the risk of death from endometrial cancer, cardiovascular disease and intercurrent disease. Relapse of disease appeared to be reduced by progestagen therapy in one trial (HR = 0.71, 95% CI 0.52 to 0.97 and 5 year RR = 0.74, 95% CI 0.58 to 0.96), but there was no evidence of a difference in disease recurrence in another trial at 7 years (RR = 1.34, 95% CI 0.79 to 2.27). Authors’ conclusions There

  15. Gene Tests May Improve Therapy for Endometrial Cancer

    MedlinePlus

    ... External link, please review our exit disclaimer . Subscribe Gene Tests May Improve Therapy for Endometrial Cancer By analyzing genes in hundreds of endometrial tumors, scientists identified details ...

  16. Endometrial carcinoma arising in a bicornuate uterus

    PubMed Central

    Munkhdelger, Jijgee; Mia-Jan, Khalilullah; Cha, Dong Soo

    2014-01-01

    Endometrial carcinomas arising in a bicornuate uterus are rare, only five case of which have been previously reported. We present a case of endometrial cancer arising in a bicornuate uterus, occurring in a 65-year-old woman. Unlike previously reported cases, our case showed mixed endometrial adenocarcinoma and undifferentiated carcinoma in one horn and focal adenocarcinoma in the other. Adequate tissue sampling of both horns is necessary for accurate diagnosis of malignancy in patients with a bicornuate uterus. Physicians should be aware of the possibility of this abnormality in cases when endometrial cancer is suspected but histology fails to confirm. PMID:25264532

  17. Endometrial aspiration cytology in gynecological disorders

    PubMed Central

    Jadhav, Meenal V.; Phatke, Anjali S.; Kadgi, Nalini Vinayak; Rane, Sharda R.; Kulkarni, Kalpana K.

    2016-01-01

    Context: Endometrial aspiration is not a popular modality for the study of the endometrium despite its simplicity and potential utility. Aim: The present study was aimed at evaluating the utility of endometrial aspiration in various gynecological disorders. Materials and Methods: In this diagnostic accuracy study, 55 prospectively registered women with various gynecological disorders were evaluated clinically and subjected to endometrial aspiration cytology and study of endometrial histology. Endometrial aspiration was performed by infant feeding tube in 10 cases and intra cath cannula in 45 cases. The slides were stained with rapid Papanicolaou (PAP) stain and Leishman stain. Results: Endometrial aspiration cytology showed 90% and 94.6% sampling adequacy with infant feeding tube and intra cath cannula, respectively. Intra cath cannula was very convenient to handle and superior to infant feeding tube in aspirating the endometrium. Of the two stains used, rapid PAP stain was less time-consuming and superior to Leishman stain in studying the nuclear details. Leishman stain was helpful in detecting cytoplasmic vacuoles of secretory endometrium. Overall diagnostic accuracy of endometrial cytology was 90.4% while that for morphological hormonal evaluation was 97.6%. It enjoyed a sensitivity of 91.66%, a specificity of 88.23%, positive predictive value of 94.28%, and negative predictive value of 83.33%. Conclusion: Intra cath cannula emerged as an inexpensive, effective, and convenient device for endometrial aspiration. Endometrial aspiration proved to be a fairly effective, simple, and informative diagnostic modality. PMID:27011435

  18. Comparative Cistromics Reveals Genomic Cross-talk between FOXA1 and ERα in Tamoxifen-Associated Endometrial Carcinomas.

    PubMed

    Droog, Marjolein; Nevedomskaya, Ekaterina; Kim, Yongsoo; Severson, Tesa; Flach, Koen D; Opdam, Mark; Schuurman, Karianne; Gradowska, Patrycja; Hauptmann, Michael; Dackus, Gwen; Hollema, Harry; Mourits, Marian; Nederlof, Petra; van Boven, Hester; Linn, Sabine C; Wessels, Lodewyk; van Leeuwen, Flora E; Zwart, Wilbert

    2016-07-01

    Tamoxifen, a small-molecule antagonist of the transcription factor estrogen receptor alpha (ERα) used to treat breast cancer, increases risks of endometrial cancer. However, no parallels of ERα transcriptional action in breast and endometrial tumors have been found that might explain this effect. In this study, we addressed this issue with a genome-wide assessment of ERα-chromatin interactions in surgical specimens obtained from patients with tamoxifen-associated endometrial cancer. ERα was found at active enhancers in endometrial cancer cells as marked by the presence of RNA polymerase II and the histone marker H3K27Ac. These ERα binding sites were highly conserved between breast and endometrial cancer and enriched in binding motifs for the transcription factor FOXA1, which displayed substantial overlap with ERα binding sites proximal to genes involved in classical ERα target genes. Multifactorial ChIP-seq data integration from the endometrial cancer cell line Ishikawa illustrated a functional genomic network involving ERα and FOXA1 together with the enhancer-enriched transcriptional regulators p300, FOXM1, TEAD4, FNFIC, CEBP8, and TCF12. Immunohistochemical analysis of 230 primary endometrial tumor specimens showed that lack of FOXA1 and ERα expression was associated with a longer interval between breast cancer and the emergence of endometrial cancer, exclusively in tamoxifen-treated patients. Our results define conserved sites for a genomic interplay between FOXA1 and ERα in breast cancer and tamoxifen-associated endometrial cancer. In addition, FOXA1 and ERα are associated with the interval time between breast cancer and endometrial cancer only in tamoxifen-treated breast cancer patients. Cancer Res; 76(13); 3773-84. ©2016 AACR. PMID:27197147

  19. A Procedure for Analyzing Classroom Dialogue.

    ERIC Educational Resources Information Center

    Clarke, John A.

    Classroom dialogue is an important influence on students' learning, making the structure and content of dialogue important research variables. An analysis of two sample classroom dialogues using the Thematic and Structural Analysis (TSA) Technique shows a positive correlation between the quality of dialogue structure and the level of student…

  20. Improving the Efficiency of Dialogue in Tutoring

    ERIC Educational Resources Information Center

    Kopp, Kristopher J.; Britt, M. Anne; Millis, Keith; Graesser, Arthur C.

    2012-01-01

    The current studies investigated the efficient use of dialogue in intelligent tutoring systems that use natural language interaction. Such dialogues can be relatively time-consuming. This work addresses the question of how much dialogue is needed to produce significant learning gains. In Experiment 1, a full dialogue condition and a read-only…

  1. Design of Man-Computer Dialogues.

    ERIC Educational Resources Information Center

    Martin, James

    An attempt is made to provide a comprehensive guide to design of the dialogues between man and computer that take place at computer terminals. Particular topics include problems with conventional alphanumeric dialogues, dialogues with sound and graphics, pyschological characteristics of computer terminal users, problems of designing dialogues for…

  2. Minireview: Steroid-regulated paracrine mechanisms controlling implantation.

    PubMed

    Pawar, Sandeep; Hantak, Alison M; Bagchi, Indrani C; Bagchi, Milan K

    2014-09-01

    Implantation is an essential process during establishment of pregnancy in mammals. It is initiated with the attachment of the blastocyst to a receptive uterine epithelium followed by its invasion into the stromal tissue. These events are profoundly regulated by the steroid hormones 17β-estradiol and progesterone. During the past several years, mouse models harboring conditional gene knockout mutations have become powerful tools for determining the functional roles of cellular factors involved in various aspects of implantation biology. Studies using these genetic models as well as primary cultures of human endometrial cells have established that the estrogen receptor α, the progesterone receptor, and their downstream target genes critically regulate uterine growth and differentiation, which in turn control embryo-endometrial interactions during early pregnancy. These studies have uncovered a diverse array of molecular cues, which are produced under the influence of estrogen receptor α and progesterone receptor and exchanged between the epithelial and stromal compartments of the uterus during the progressive phases of implantation. These paracrine signals are critical for acquisition of uterine receptivity and functional interactions with the embryo. This review highlights recent work describing paracrine mechanisms that govern steroid-regulated uterine epithelial-stromal dialogue during implantation and their roles in fertility and disease. PMID:25051170

  3. Endometrial cancer arising from atypical complex hyperplasia: The significance in an endometrial biopsy and a diagnostic challenge

    PubMed Central

    Byun, Jung Mi; Jeong, Dae Hoon; Kim, Young Nam; Cho, En Bee; Cha, Ju Eun; Sung, Moon Su; Lee, Kyung Bok

    2015-01-01

    Objective We investigated the features of endometrial hyperplasia with concurrent endometrial cancer that had been diagnosed by endometrial sampling. Further, we attempted to identify an accurate differential diagnostic method. Methods We retrospectively studied 125 patients who underwent a diagnostic endometrial biopsy or were diagnosed after the surgical treatment of other gynecological lesions, such as leiomyoma or polyps. Patients were diagnosed between January 2005 and December 2013 at Busan Paik Hospital. Clinical and histopathological characteristics were compared in patients who had atypical endometrial hyperplasia with and without concurrent endometrial cancer. Results The patients were grouped based on the final pathology reports. One hundred seventeen patients were diagnosed with endometrial hyperplasia and eight patients were diagnosed with endometrioid adenocarcinoma arising from atypical hyperplasia. Of the 26 patients who had been diagnosed with atypical endometrial hyperplasia by office-based endometrial biopsy, eight (30.8%) were subsequently diagnosed with endometrial cancer after they had undergone hysterectomy. The patients with endometrial cancer arising from endometrial hyperplasia were younger (39.1 vs. 47.2 years, P=0.0104) and more obese (body mass index 26.1±9.6 vs. 23.8±2.8 kg/m2, P=0.3560) than the patients with endometrial hyperplasia. The correlation rate between the pathology of the endometrial samples and the final diagnosis of endometrial hyperplasia was 67.3%. Conclusion In patients with atypical endometrial hyperplasia, the detection of endometrial cancer before hysterectomy can decrease the risk of suboptimal treatment. The accuracy of endometrial sampling for the diagnosis of concurrent endometrial carcinoma was much lower than that for atypical endometrial hyperplasia. Therefore, concurrent endometrial carcinoma should be suspected and surgical intervention should be considered in young or obese patients who present with

  4. 21 CFR 884.1100 - Endometrial brush.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Endometrial brush. 884.1100 Section 884.1100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES OBSTETRICAL AND GYNECOLOGICAL DEVICES Obstetrical and Gynecological Diagnostic Devices § 884.1100 Endometrial brush. (a) Identification....

  5. 21 CFR 884.1060 - Endometrial aspirator.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Endometrial aspirator. 884.1060 Section 884.1060 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES OBSTETRICAL AND GYNECOLOGICAL DEVICES Obstetrical and Gynecological Diagnostic Devices § 884.1060 Endometrial aspirator....

  6. 21 CFR 884.1060 - Endometrial aspirator.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Endometrial aspirator. 884.1060 Section 884.1060 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES OBSTETRICAL AND GYNECOLOGICAL DEVICES Obstetrical and Gynecological Diagnostic Devices § 884.1060 Endometrial aspirator....

  7. 21 CFR 884.1185 - Endometrial washer.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Endometrial washer. 884.1185 Section 884.1185 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES OBSTETRICAL AND GYNECOLOGICAL DEVICES Obstetrical and Gynecological Diagnostic Devices § 884.1185 Endometrial washer. (a) Identification....

  8. 21 CFR 884.1185 - Endometrial washer.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Endometrial washer. 884.1185 Section 884.1185 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES OBSTETRICAL AND GYNECOLOGICAL DEVICES Obstetrical and Gynecological Diagnostic Devices § 884.1185 Endometrial washer. (a) Identification....

  9. 21 CFR 884.1100 - Endometrial brush.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Endometrial brush. 884.1100 Section 884.1100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES OBSTETRICAL AND GYNECOLOGICAL DEVICES Obstetrical and Gynecological Diagnostic Devices § 884.1100 Endometrial brush. (a) Identification....

  10. Endometrial polyps in 2 African pygmy hedgehogs

    PubMed Central

    2005-01-01

    Abstract Reports of spontaneously occurring endometrial polyps in animals are rare and have only involved a few species. This report is intended to advise veterinarians that older African pygmy hedgehogs may develop endometrial polyps and that these lesions can be a cause of bloody vaginal discharge, sometimes interpreted as hematuria. PMID:16048013

  11. Diagnosis and Management of Endometrial Cancer.

    PubMed

    Braun, Michael M; Overbeek-Wager, Erika A; Grumbo, Robert J

    2016-03-15

    Endometrial cancer is the most common gynecologic malignancy. It is the fourth most common cancer in women in the United States after breast, lung, and colorectal cancers. Risk factors are related to excessive unopposed exposure of the endometrium to estrogen, including unopposed estrogen therapy, early menarche, late menopause, tamoxifen therapy, nulliparity, infertility or failure to ovulate, and polycystic ovary syndrome. Additional risk factors are increasing age, obesity, hypertension, diabetes mellitus, and hereditary nonpolyposis colorectal cancer. The most common presentation for endometrial cancer is postmenopausal bleeding. The American Cancer Society recommends that all women older than 65 years be informed of the risks and symptoms of endometrial cancer and advised to seek evaluation if symptoms occur. There is no evidence to support endometrial cancer screening in asymptomatic women. Evaluation of a patient with suspected disease should include a pregnancy test in women of childbearing age, complete blood count, and prothrombin time and partial thromboplastin time if bleeding is heavy. Most guidelines recommend either transvaginal ultrasonography or endometrial biopsy as the initial study. The mainstay of treatment for endometrial cancer is total hysterectomy with bilateral salpingo-oophorectomy. Radiation and chemotherapy can also play a role in treatment. Low- to medium-risk endometrial hyperplasia can be treated with nonsurgical options. Survival is generally defined by the stage of the disease and histology, with most patients at stage I and II having a favorable prognosis. Controlling risk factors such as obesity, diabetes, and hypertension could play a role in the prevention of endometrial cancer. PMID:26977831

  12. Novel genetic targets in endometrial cancer

    PubMed Central

    Bell, Daphne W.

    2014-01-01

    Worldwide, ~74,000 women die from endometrial cancer each year. Understanding the somatic genomic alterations that drive endometrial tumorigenesis may provide new opportunities to identify targeted therapies for specific subsets of patients. Since 2012, the use of next generation sequencing to decode the mutational landscape of endometrial tumors has not only confirmed prior knowledge of established genetic targets for serous and endometrioid endometrial carcinomas, but has also uncovered novel significantly mutated genes, referred to herein as novel genetic targets, which represent candidate cancer genes in these tumors. This editorial summarizes the novel genetic targets that have been identified in serous and endometrioid ECs, according to their unifying functional characteristics. An expert opinion section comments on remaining knowledge gaps that will undoubtedly be filled in future genomic studies of endometrial cancer. PMID:24750045

  13. Evaluation of endometrial cancer epidemiology in Romania.

    PubMed

    Bohîlțea, R E; Furtunescu, F; Dosius, M; Cîrstoiu, M; Radoi, V; Baroș, A; Bohîlțea, L C

    2015-01-01

    Endometrial cancer represents the most frequent gynecological malignant affection in the developed countries, in which the incidence of cervical cancer has significantly decreased due to the rigorous application of screening methods and prophylaxis. According to its frequency, endometrial cancer is situated on the fourth place in the category of women's genital-mammary malignant diseases, after breast, cervical and ovarian cancer in Romania. The incidence and mortality rates due to endometrial cancer have registered an increasing trend worldwide and also in Romania, a significant decrease of the age of appearance for the entire endometrial pathology sphere being noticed. At the national level, the maximum incidence is situated between 60 and 64 years old, the mortality rate of the women under 65 years old being high in Romania. The study evaluates endometrial cancer, from an epidemiologic point of view, at the national level compared to the international statistic data. PMID:25866582

  14. Evaluation of endometrial cancer epidemiology in Romania

    PubMed Central

    Bohîlțea, RE; Furtunescu, F; Dosius, M; Cîrstoiu, M; Radoi, V; Baroș, A; Bohîlțea, LC

    2015-01-01

    Endometrial cancer represents the most frequent gynecological malignant affection in the developed countries, in which the incidence of cervical cancer has significantly decreased due to the rigorous application of screening methods and prophylaxis. According to its frequency, endometrial cancer is situated on the fourth place in the category of women’s genital-mammary malignant diseases, after breast, cervical and ovarian cancer in Romania. The incidence and mortality rates due to endometrial cancer have registered an increasing trend worldwide and also in Romania, a significant decrease of the age of appearance for the entire endometrial pathology sphere being noticed. At the national level, the maximum incidence is situated between 60 and 64 years old, the mortality rate of the women under 65 years old being high in Romania. The study evaluates endometrial cancer, from an epidemiologic point of view, at the national level compared to the international statistic data. PMID:25866582

  15. Sunitinib Malate in Treating Patients With Recurrent or Metastatic Endometrial Cancer

    ClinicalTrials.gov

    2016-07-26

    Endometrial Adenocarcinoma; Endometrial Endometrioid Adenocarcinoma; Endometrial Serous Adenocarcinoma; Recurrent Uterine Corpus Carcinoma; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer; Uterine Carcinosarcoma; Uterine Corpus Carcinosarcoma

  16. [The role of miRNA in endometrial cancer in the context of miRNA 205].

    PubMed

    Wilczyński, Miłosz; Danielska, Justyna; Dzieniecka, Monika; Malinowski, Andrzej

    2015-11-01

    MiRNAs are small, non-coding molecules of ribonucleic acids of approximately 22 bp length, which serve as regulators of gene expression and protein translation due to interference with messenger RNA (mRNA). MiRNAs, which take part in the regulation of cell cycle and apoptosis, may be associated with carcinogenesis. Aberrant expression of miRNAs in endometrial cancer might contribute to the endometrial cancer initiation or progression, as well as metastasis formation, and may influence cancer invasiveness. Specific-miRNAs expressed in endometrial cancer tissues may serve as diagnostic markers of the disease, prognostic biomarkers, or play an important part in oncological therapy We aimed to describe the role of miRNAs in endometrial cancer with special consideration of miRNA 205. PMID:26817318

  17. Addressivity in cogenerative dialogues

    NASA Astrophysics Data System (ADS)

    Hsu, Pei-Ling

    2014-03-01

    Ashraf Shady's paper provides a first-hand reflection on how a foreign teacher used cogens as culturally adaptive pedagogy to address cultural misalignments with students. In this paper, Shady drew on several cogen sessions to showcase his journey of using different forms of cogens with his students. To improve the quality of cogens, one strategy he used was to adjust the number of participants in cogens. As a result, some cogens worked and others did not. During the course of reading his paper, I was impressed by his creative and flexible use of cogens and at the same time was intrigued by the question of why some cogens work and not others. In searching for an answer, I found that Mikhail Bakhtin's dialogism, especially the concept of addressivity, provides a comprehensive framework to address this question. In this commentary, I reanalyze the cogen episodes described in Shady's paper in the light of dialogism. My analysis suggests that addressivity plays an important role in mediating the success of cogens. Cogens with high addressivity function as internally persuasive discourse that allows diverse consciousnesses to coexist and so likely affords productive dialogues. The implications of addressivity in teaching and learning are further discussed.

  18. Endometrial Exosomes/Microvesicles in the Uterine Microenvironment: A New Paradigm for Embryo-Endometrial Cross Talk at Implantation

    PubMed Central

    Ng, York Hunt; Rome, Sophie; Jalabert, Audrey; Forterre, Alexis; Singh, Harmeet; Hincks, Cassandra L.; Salamonsen, Lois A.

    2013-01-01

    Exosomes are nanoparticles (∼100 nm diameter) released from cells, which can transfer small RNAs and mRNA via the extracellular environment to cells at distant sites. We hypothesised that exosomes or the slightly larger microvesicles (100–300 nm) are released from the endometrial epithelium into the uterine cavity, and that these contain specific micro (mi)RNA that could be transferred to either the trophectodermal cells of the blastocyst or to endometrial epithelial cells, to promote implantation. The aim of this study was to specifically identify and characterise exosomes/microvesicles (mv) released from endometrial epithelial cells and to determine whether exosomes/mv are present in uterine fluid. Immunostaining demonstrated that the tetraspanins, CD9 and CD63 used as cell surface markers of exosomes are present on the apical surfaces of endometrial epithelial cells in tissue sections taken across the menstrual cycle: CD63 showed cyclical regulation. Exosome/mv pellets were prepared from culture medium of endometrial epithelial cell (ECC1 cells) and from uterine fluid and its associated mucus by sequential ultracentifugation. Exosomes/mv were positively identified in all preparations by FACS and immunofluorescence staining following exosome binding to beads. Size particle analysis confirmed the predominance of particles of 50–150 nm in each of these fluids. MiRNA analysis of the ECC1 cells and their exosomes/mv demonstrated sorting of miRNA into exosomes/mv: 13 of the 227 miRNA were specific to exosomes/mv, while a further 5 were not present in these. The most abundant miRNA in exosomes/mv were hsa-miR-200c, hsa-miR-17 and hsa-miR-106a. Bioinformatic analysis showed that the exosome/mv-specific miRNAs have potential targets in biological pathways highly relevant for embryo implantation. Thus exosomes/mv containing specific miRNA are present in the microenvironment in which embryo implantation occurs and may contribute to the endometrial-embryo cross talk

  19. Fibulin-5 localisation in human endometrial cancer shifts from epithelial to stromal with increasing tumour grade, and silencing promotes endometrial epithelial cancer cell proliferation

    PubMed Central

    WINSHIP, AMY LOUISE; RAINCZUK, KATE; TON, AMANDA; DIMITRIADIS, EVA

    2016-01-01

    Endometrial cancer is the most common invasive gynaecological malignancy. While endocrine, genetic and inflammatory factors are thought to contribute to its pathogenesis, its precise etiology and molecular regulators remain poorly understood. Fibulin-5 is an extracellular matrix (ECM) protein that inhibits cell growth and invasion in several cancer cell types and is downregulated in a number of types of human cancer. However, it is unknown whether fibulin-5 plays a role in endometrial tumourigenesis. In the current report, the expression and localisation of fibulin-5 in type I endometrioid human endometrial cancers of grades (G) 1–3 was investigated using reverse transcription-quantitative polymerase chain reaction and immunohistochemistry. Fibulin-5 mRNA was found to be significantly reduced in whole tumour tissues from women across G1-3 compared with benign endometrium (P<0.0001). Consistently, fibulin-5 protein was also reduced in the tumour epithelial compartment across increasing tumour grades. By contrast, increased protein localisation to the tumour stroma was observed with increasing grade. Knockdown by small interfering RNA in Ishikawa endometrial epithelial cancer cells expressing fibulin-5 stimulated cell adhesion and proliferation in vitro. Fibulin-5 mRNA expression in Ishikawa cells was induced by transforming growth factor-β and fibulin-5 in turn activated extracellular signal-regulated kinases (ERK1/2), suggesting that it may act via the mitogen-activated protein kinase pathway. In summary, the present study identified fibulin-5 as a downregulated ECM gene in human endometrial cancer and observed a shift from epithelial to stromal protein localisation with increasing tumour grade in women. These data suggest that loss of fibulin-5 function may promote endometrial cancer progression by enhancing epithelial cell adhesion and proliferation. PMID:27347195

  20. The Inflammation Response to DEHP through PPARγ in Endometrial Cells

    PubMed Central

    Huang, Qiansheng; Zhang, Huanteng; Chen, Ya-Jie; Chi, Yu-Lang; Dong, Sijun

    2016-01-01

    Epidemiological studies have shown the possible link between phthalates and endometrium-related gynecological diseases, however the molecular mechanism(s) behind this is/are still unclear. In the study, both primary cultured endometrial cells and an endometrial adenocarcinoma cell line (Ishikawa) were recruited to investigate the effects of di-(2-ethylhexyl) phthalate (DEHP) at human-relevant concentrations. The results showed that DEHP did not affect the viability of either type of cell, which showed different responses to inflammation. Primary cultured cells showed stronger inflammatory reactions than the Ishikawa cell line. The expression of inflammatory factors was induced both at the mRNA and protein levels, however the inflammation did not induce the progress of epithelial-mesenchymal transition (EMT) as the protein levels of EMT markers were not affected after exposure to either cell type. Further study showed that the mRNA levels of peroxisome proliferator-activated receptor gamma (PPARγ) wereup-regulated after exposure. In all, our study showed that human-relevant concentrations of DEHP could elicit the inflammatory response in primary cultured endometrial cells rather than in Ishikawa cell line. PPARγ may act as the mediating receptor in the inflammation reaction. PMID:26985901

  1. The Inflammation Response to DEHP through PPARγ in Endometrial Cells.

    PubMed

    Huang, Qiansheng; Zhang, Huanteng; Chen, Ya-Jie; Chi, Yu-Lang; Dong, Sijun

    2016-03-01

    Epidemiological studies have shown the possible link between phthalates and endometrium-related gynecological diseases, however the molecular mechanism(s) behind this is/are still unclear. In the study, both primary cultured endometrial cells and an endometrial adenocarcinoma cell line (Ishikawa) were recruited to investigate the effects of di-(2-ethylhexyl) phthalate (DEHP) at human-relevant concentrations. The results showed that DEHP did not affect the viability of either type of cell, which showed different responses to inflammation. Primary cultured cells showed stronger inflammatory reactions than the Ishikawa cell line. The expression of inflammatory factors was induced both at the mRNA and protein levels, however the inflammation did not induce the progress of epithelial-mesenchymal transition (EMT) as the protein levels of EMT markers were not affected after exposure to either cell type. Further study showed that the mRNA levels of peroxisome proliferator-activated receptor gamma (PPARγ) wereup-regulated after exposure. In all, our study showed that human-relevant concentrations of DEHP could elicit the inflammatory response in primary cultured endometrial cells rather than in Ishikawa cell line. PPARγ may act as the mediating receptor in the inflammation reaction. PMID:26985901

  2. Sonohysterography: a technique for endometrial evaluation.

    PubMed

    Cullinan, J A; Fleischer, A C; Kepple, D M; Arnold, A L

    1995-05-01

    Sonohysterography involves the instillation of sterile saline under continuous sonographic visualization to assess the endometrial cavity. The technique is most useful for evaluating women with fertility problems, postmenopausal bleeding, or an abnormal endometrial interface as seen at baseline sonography. The procedure is performed with saline instilled into the endometrial cavity through a 5-F pediatric feeding tube or a hysterosalpingography or insemination catheter. In the normal uterus, the endometrium appears symmetric, surrounding the anechoic, saline-distended endometrial cavity. Adhesions appear as bridging bands of tissue that distort the uterine cavity or as very thin, undulating membranes, best seen at real-time examination. An intracavitary polyp is seen surrounded by anechoic fluid, with the point of attachment and thickness of the stalk clearly demonstrated. The location of leiomyomas can be determined: Intramural lesions do not distort the endometrial cavity, whereas submucosal lesions often do, with the overlying normal layer of endometrium clearly seen. In women with abnormal bleeding, focal areas of asymmetric endometrial thickening can be identified. Sonohysterography allows differentiation of intracavitary, endometrial, and submucosal abnormalities without the use of ionizing radiation or contrast agents. PMID:7624559

  3. The dialogue goes on.

    PubMed

    Salas, R M

    1975-01-01

    A worldwide dialogue on population began in 1974, World Population Year, in Bucharest. Although there was a general awareness among the delegates at the World Population Conference that the population issue is beyond the ideological background, no consensus on the definition of the problem was reached. Some saw it as a currently unsustainable increase in the number of people dependent on available resources; some viewed it as a question of density; others believed it to be a "national pride" issue relating to insufficient hands available to develop national resources to their full potential; politicians spoke of the issue as a political matter; technicians saw it as a need for programs of action through which information and equipment for limiting fertility could be available to those who sought it; and the economic planners regarded the problem as a need for a balance between people and resources. It has become necessary to view the population issue as an integral and essential factor in development planning and programming. A 2-way line of communication between people and planners is crucial. This was the reason for the Fund's support of continuing programs of training and briefing communicators interested in effecting social change. The Year allowed several hundred editors, writers and broadcasters to commit themselves as individuals and professionals to the urgent population question. Several thousand members of nongovernmental and other institutions and private individuals were also given the opportunity to search for the ideas, techniques, values and priorities that will lead to solutions. The newsletter acts as a communication vehicle to sustain public commitment. It is also a measure of the responsiveness that UNFPA has adopted as one of its cardinal principles. PMID:12312922

  4. Endometrial receptivity array: Clinical application.

    PubMed

    Mahajan, Nalini

    2015-01-01

    Human implantation is a complex process requiring synchrony between a healthy embryo and a functionally competent or receptive endometrium. Diagnosis of endometrial receptivity (ER) has posed a challenge and so far most available tests have been subjective and lack accuracy and a predictive value. Microarray technology has allowed identification of the transcriptomic signature of the window of receptivity window of implantation (WOI). This technology has led to the development of a molecular diagnostic tool, the ER array (ERA) for diagnosis of ER. Use of this test in patients with recurrent implantation failure (RIF) has shown that the WOI is displaced in a quarter of these patients and use of a personalized embryo transfer (pET) on the day designated by ERA improves reproductive performance. Our results in the Indian population revealed an endometrial factor in 27.5% RIF patients, which was significantly greater than the non-RIF group 15% (P = 0.04). After pET, the overall ongoing pregnancy rate was 42.4% and implantation rate was 33%, which was at par with our in-vitro fertilization results over 1-year. We also performed ERA in patients with persistently thin endometrium, and it was reassuring to find that the endometrium in 75% of these patients was receptive despite being 6 mm or less. A pregnancy rate of 66.7% was achieved in this group. Though larger studies are required to validate these results ERA has become a useful tool in our diagnostic armamentarium for ER. PMID:26538853

  5. Endometrial receptivity array: Clinical application

    PubMed Central

    Mahajan, Nalini

    2015-01-01

    Human implantation is a complex process requiring synchrony between a healthy embryo and a functionally competent or receptive endometrium. Diagnosis of endometrial receptivity (ER) has posed a challenge and so far most available tests have been subjective and lack accuracy and a predictive value. Microarray technology has allowed identification of the transcriptomic signature of the window of receptivity window of implantation (WOI). This technology has led to the development of a molecular diagnostic tool, the ER array (ERA) for diagnosis of ER. Use of this test in patients with recurrent implantation failure (RIF) has shown that the WOI is displaced in a quarter of these patients and use of a personalized embryo transfer (pET) on the day designated by ERA improves reproductive performance. Our results in the Indian population revealed an endometrial factor in 27.5% RIF patients, which was significantly greater than the non-RIF group 15% (P = 0.04). After pET, the overall ongoing pregnancy rate was 42.4% and implantation rate was 33%, which was at par with our in-vitro fertilization results over 1-year. We also performed ERA in patients with persistently thin endometrium, and it was reassuring to find that the endometrium in 75% of these patients was receptive despite being 6 mm or less. A pregnancy rate of 66.7% was achieved in this group. Though larger studies are required to validate these results ERA has become a useful tool in our diagnostic armamentarium for ER. PMID:26538853

  6. Sirtuin 1 promotes the growth and cisplatin resistance of endometrial carcinoma cells: a novel therapeutic target.

    PubMed

    Asaka, Ryoichi; Miyamoto, Tsutomu; Yamada, Yasushi; Ando, Hirofumi; Mvunta, David Hamisi; Kobara, Hisanori; Shiozawa, Tanri

    2015-12-01

    Sirtuin 1 (SIRT1), originally identified as a longevity gene, is induced by caloric restriction, and regulates various cellular functions including DNA repair, cell survival and metabolism via the deacetylation of target proteins such as histone and p53. These functions are considered to act dualistically as preventing or facilitating cancer. This study aimed to clarify the expression and role of SIRT1 in endometrial carcinoma. Because a high-calorie diet was a well-known risk factor for endometrial carcinoma, we first hypothesized that SIRT1 might be downregulated in normal endometrial glandular cells of obese women. However, no correlation was observed between the expression of SIRT1 and body mass index (BMI). In contrast, regardless of BMI, the immunohistochemical expression of SIRT1 was significantly higher in endometrial carcinoma (108 cases) than in normal endometria (60 cases) (P<0.05), and its overexpression was associated with a shorter survival (P<0.05). Our experiments in vivo revealed that SIRT1 accelerated the proliferation of endometrial carcinoma cell lines (HHUA, HEC151, and HEC1B). SIRT1 overexpression significantly enhanced the resistance for cisplatin and paclitaxel in HHUA cells. Although p53 is an important target protein for SIRT1, the selective SIRT1 inhibitor (EX527) significantly suppressed the proliferation and cisplatin resistance of three endometrial carcinoma cell lines regardless of the p53 mutation status. In addition, SIRT1 overexpression in HHUA cells accelerated tumor growth and cisplatin resistance in nude mice, and EX527 significantly suppressed the growth of tumors of HHUA and HEC1B cells. No adverse effect of EX527 was observed in these mice. In conclusion, SIRT1 is involved in the acquisition of the aggressive behavior associated with endometrial carcinoma, and the SIRT1 inhibitor, EX527, may be a useful agent for the treatment of this malignancy. PMID:26367491

  7. In situ androgen and estrogen biosynthesis in endometrial cancer: focus on androgen actions and intratumoral production.

    PubMed

    Ito, Kiyoshi; Miki, Yasuhiro; Suzuki, Takashi; McNamara, Keely May; Sasano, Hironobu

    2016-07-01

    In situ estrogen biosynthesis is considered to play pivotal roles in the development and progression of human endometrial carcinoma. However, the biological roles of androgen have remained virtually unknown. Various epidemiological studies have revealed that elevated serum androgen levels are generally associated with an increased risk of developing endometrial carcinoma; however, studies directly examining androgens in carcinoma tissues are relatively rare and reviews summarizing this information are scarce. Therefore, we summarized recent studies on androgens in endometrial carcinoma, especially focusing androgen actions and in situ androgen biosynthesis. Among the enzymes required for local biosynthesis of androgen, 17β-hydroxysteroid dehydrogenase type 5 (conversion from androstenedione to testosterone) and 5α-reductase (reduction of testosterone to dihydrotestosterone (DHT)) are the principal enzymes involved in the formation of biologically most potent androgen, DHT. Both enzymes and androgen receptor were expressed in endometrial carcinoma tissues, and in situ production of DHT has been reported to exist in endometrial carcinoma tissues. However, testosterone is not only a precursor of DHT production, but also a precursor of estradiol synthesis, as a substrate of the aromatase enzyme. Therefore, aromatase could be another key enzyme serving as a negative regulator for in situ production of DHT by reducing amounts of the precursor. In an in vitro study, DHT was reported to exert antiproliferative effects on endometrial carcinoma cells. Intracrine mechanisms of androgens, the downstream signals of AR, which are directly related to anticancer progression, and the clinical significance of DHT-AR pathway in the patients with endometrial carcinoma have, however, not been fully elucidated. PMID:27287451

  8. Endometrial Stromal Decidualization Responds Reversibly to Hormone Stimulation and Withdrawal.

    PubMed

    Yu, Jie; Berga, Sarah L; Johnston-MacAnanny, Erika B; Sidell, Neil; Bagchi, Indrani C; Bagchi, Milan K; Taylor, Robert N

    2016-06-01

    Human endometrial stromal decidualization is required for embryo receptivity, angiogenesis, and placentation. Previous studies from our laboratories established that connexin (Cx)-43 critically regulates endometrial stromal cell (ESC) differentiation, whereas gap junction blockade prevents it. The current study evaluated the plasticity of ESC morphology and Cx43 expression, as well as other biochemical markers of cell differentiation, in response to decidualizing hormones. Primary human ESC cultures were exposed to 10 nM estradiol, 100 nM progesterone, and 0.5 mM cAMP for up to 14 days, followed by hormone withdrawal for 14 days, mimicking a biphasic ovulatory cycle. Reversible differentiation was documented by characteristic changes in cell shape. Cx43 was reversibly up- and down-regulated after the estradiol, progesterone, and cAMP treatment and withdrawal, respectively, paralleled by fluctuations in prolactin, vascular endothelial growth factor, IL-11, and glycodelin secretion. Markers of mesenchymal-epithelial transition (MET), and its counterpart epithelial-mesenchymal transition, followed reciprocal patterns corresponding to the morphological changes. Incubation in the presence of 18α-glycyrrhetinic acid, an inhibitor of gap junctions, partially reversed the expression of decidualization and MET markers. In the absence of hormones, Cx43 overexpression promoted increases in vascular endothelial growth factor and IL-11 secretion, up-regulated MET markers, and reduced N-cadherin, an epithelial-mesenchymal transition marker. The combined results support the hypothesis that Cx43-containing gap junctions and endocrine factors cooperate to regulate selected biomarkers of stromal decidualization and MET and suggest roles for both phenomena in endometrial preparation for embryonic receptivity. PMID:27035651

  9. The clinical management of inoperable endometrial carcinoma.

    PubMed

    Palisoul, Marguerite; Mutch, David G

    2016-05-01

    Unresectable endometrial cancer, while rare, has a very poor prognosis, with a survival rate of 2 to 8 months. Although endometrial cancer is generally regarded as a survivable disease, the less common advanced and aggressive forms account for a large portion of endometrial cancer related deaths. Given the paucity of inoperable disease, randomized clinical data is lacking in this specific patient population. Management decisions regarding radiation therapy or systemic therapy are largely guided by the existing data in the setting of recurrence or second-line treatment, adjuvant therapy following optimal debulking, or in patients who are considered inoperable due to medical comorbidities rather than the extent of their disease. PMID:26999568

  10. Cabozantinib-S-Malate in Treating Patients With Recurrent or Metastatic Endometrial Cancer

    ClinicalTrials.gov

    2016-07-04

    Endometrial Adenosquamous Carcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Mixed Adenocarcinoma; Endometrial Serous Adenocarcinoma; Metastatic Endometrioid Adenocarcinoma; Recurrent Uterine Corpus Carcinoma; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer

  11. Breast cancer susceptibility polymorphisms and endometrial cancer risk: a Collaborative Endometrial Cancer Study

    PubMed Central

    Ahmed, Shahana; O’Mara, Tracy A.; Ferguson, Kaltin; Lambrechts, Diether; Garcia-Dios, Diego A.; Vergote, Ignace; Amant, Frederic; Howarth, Kimberley; Gorman, Maggie; Hodgson, Shirley; Tomlinson, Ian; Yang, Hannah P.; Lissowska, Jolanta; Brinton, Louise A.; Chanock, Stephen; Garcia-Closas, Montserrat; Hall, Per; Liu, Jianjun; Shah, Mitul; Pharoah, Paul D.P.; Thompson, Deborah J.; Rebbeck, Timothy R.; Strom, Brian L.; Dunning, Alison M.; Easton, Douglas F.; Spurdle, Amanda B.

    2011-01-01

    Recent large--scale association studies, both of genome-wide and candidate gene design, have revealed several single-nucleotide polymorphisms (SNPs) which are significantly associated with risk of developing breast cancer. As both breast and endometrial cancers are considered to be hormonally driven and share multiple risk factors, we investigated whether breast cancer risk alleles are also associated with endometrial cancer risk. We genotyped nine breast cancer risk SNPs in up to 4188 endometrial cases and 11 928 controls, from between three and seven Caucasian populations. None of the tested SNPs showed significant evidence of association with risk of endometrial cancer. PMID:21965274

  12. Breast cancer susceptibility polymorphisms and endometrial cancer risk: a Collaborative Endometrial Cancer Study.

    PubMed

    Healey, Catherine S; Ahmed, Shahana; O'Mara, Tracy A; Ferguson, Kaltin; Lambrechts, Diether; Garcia-Dios, Diego A; Vergote, Ignace; Amant, Frederic; Howarth, Kimberley; Gorman, Maggie; Hodgson, Shirley; Tomlinson, Ian; Yang, Hannah P; Lissowska, Jolanta; Brinton, Louise A; Chanock, Stephen; Garcia-Closas, Montserrat; Hall, Per; Liu, Jianjun; Shah, Mitul; Pharoah, Paul D P; Thompson, Deborah J; Rebbeck, Timothy R; Strom, Brian L; Dunning, Alison M; Easton, Douglas F; Spurdle, Amanda B

    2011-12-01

    Recent large--scale association studies, both of genome-wide and candidate gene design, have revealed several single-nucleotide polymorphisms (SNPs) which are significantly associated with risk of developing breast cancer. As both breast and endometrial cancers are considered to be hormonally driven and share multiple risk factors, we investigated whether breast cancer risk alleles are also associated with endometrial cancer risk. We genotyped nine breast cancer risk SNPs in up to 4188 endometrial cases and 11,928 controls, from between three and seven Caucasian populations. None of the tested SNPs showed significant evidence of association with risk of endometrial cancer. PMID:21965274

  13. Prevalence of Co-existing Endometrial Carcinoma in Patients with Preoperative Diagnosis of Endometrial Hyperplasia

    PubMed Central

    Kadirogullari, Pinar; Atalay, Cemal Resat; Sari, Mustafa Erkan

    2015-01-01

    Introduction Endometrial hyperplasia has been associated with the presence of concomitant endometrial carcinoma. In this study, patients who were diagnosed with endometrial hyperplasia and had hysterectomy, determination of the incidence of endometrial cancer accompanying postoperatively and clinical parameters associated with cancer are aimed. Materials and Methods Endometrial biopsies were taken from patients for various reasons and among them 158 patients diagnosed with endometrial hyperplasia from pathologic examination results were retrospectively evaluated. All of the patient’s age, parity, weight, transvaginal ultrasound measured by endometrial thickness, concomitant systemic disease (diabetes, hypertension, hypothyroidism), tamoxifen use, hormone use and whether in reproductive age or menopause were all questioned. Patients who applied with endometrial cancer, their cervical stromal involvement, lymph node involvement, cytology positivity and omental metastases were examined. Patients were classified according to their stage and grade. Patients who had intraoperative frozen were re-evaluated. Results Fifteen cases with preoperative endometrial hyperplasia diagnosed with endometrial cancer postoperatively, 2 cases had complex hyperplasia without atypia and 13 cases had complex atypical hyperplasia. The rate of preoperative hyperplasia with postoperative endometrial cancer was found to be 10.8% where by 15 cases of patients diagnosed with endometrial cancer postoperatively 11 cases were in postmenopausal period. In patients diagnosed with endometrial cancer according to their histologic types 14 cases had endometrioid adenocarcinoma while one patient with preoperative complex hyperplasia without atypia was diagnosed with serous papillary carcinoma postoperatively. Evaluation of stages in patients diagnosed with cancer, 7 cases of patients had stage IA, 7 cases of patients had stage IB, and 7 cases cases of patients with serous papillary carcinoma were

  14. Macrophage Migration Inhibitory Factor Is Involved in Ectopic Endometrial Tissue Growth and Peritoneal-Endometrial Tissue Interaction In Vivo: A Plausible Link to Endometriosis Development

    PubMed Central

    Rakhila, Halima; Girard, Karine; Leboeuf, Mathieu; Lemyre, Madeleine

    2014-01-01

    Pelvic inflammation is a hallmark of endometriosis pathogenesis and a major cause of the disease's symptoms. Abnormal immune and inflammatory changes may not only contribute to endometriosis-major symptoms, but also contribute to ectopic endometrial tissue growth and endometriosis development. A major pro-inflammatory factors found elevated in peritoneal fluid of women with endometriosis and to be overexpressed in peritoneal fluid macrophages and active, highly vascularized and early stage endometriotic lesions, macrophage migration inhibitory factor (MIF) appeared to induce angiogenic and inflammatory and estrogen producing phenotypes in endometriotic cells in vitro and to be a possible therapeutic target in vivo. Using a mouse model where MIF-knock out (KO) mice received intra-peritoneal injection of endometrial tissue from MIF-KO or syngeneic wild type (WT) mice and vice versa, our current study revealed that MIF genetic depletion resulted in a marked reduction ectopic endometrial tissue growth, a disrupted tissue structure and a significant down regulation of the expression of major inflammatory (cyclooxygenease-2), cell adhesion (αv and β3 integrins), survival (B-cell lymphoma-2) and angiogenic (vascular endothelial cell growth) factorsrelevant to endometriosis pathogenesis, whereas MIF add-back to MIF-KO mice significantly restored endometriosis-like lesions number and size. Interestingly, cross-experiments revealed that MIF presence in both endometrial and peritoneal host tissues is required for ectopic endometrial tissue growth and pointed to its involvement in endometrial-peritoneal interactions. This study provides compelling evidence for the role of MIF in endometriosis development and its possible interest for a targeted treatment of endometriosis. PMID:25329068

  15. The epidemic of endometrial cancer: a commentary.

    PubMed Central

    Jick, H; Walker, A M; Rothman, K J

    1980-01-01

    Vital statistics show that a rise in incidence of endometrial cancer began in the mid-1960s on the West Coast of the United States. This rise was continuous and reached a peak in 1975. Elsewhere, incidence rates for endometrial cancer rose during the 1970s. It now seems evident that much of the rise in all areas of the country was due to replacement estrogen treatment. We estimated from data obtained from the Commission on Professional and Hospital Activities-Professional Activity Study of Ann Arbor, Michigan, that over 15,000 cases of endometrial cancer were caused by replacement estrogens during the five-year period 1971--1975 alone. This represents one of the largest epidemics of serious iatrogenic disease that has ever occurred in this country. With the substantial fall in estrogen sales starting in January 1976, there has been an associated decline in the incidence rates of endometrial cancer nationwide. PMID:7356090

  16. Dasatinib, Paclitaxel, and Carboplatin in Treating Patients With Stage III-IV or Recurrent Endometrial Cancer

    ClinicalTrials.gov

    2015-12-22

    Endometrial Adenocarcinoma; Endometrial Adenosquamous Carcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Mucinous Adenocarcinoma; Endometrial Serous Adenocarcinoma; Endometrial Undifferentiated Carcinoma; Endometrioid Adenocarcinoma; Recurrent Uterine Corpus Carcinoma; Stage IIIA Uterine Corpus Cancer; Stage IIIB Uterine Corpus Cancer; Stage IIIC Uterine Corpus Cancer; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer; Uterine Carcinosarcoma

  17. Reversing the reduced level of endometrial GLUT4 expression in polycystic ovary syndrome: a mechanistic study of metformin action

    PubMed Central

    Li, Xin; Cui, Peng; Jiang, Hong-Yuan; Guo, Yan-Rong; Pishdari, Bano; Hu, Min; Feng, Yi; Billig, Håkan; Shao, Ruijin

    2015-01-01

    Conflicting results have been reported regarding whether or not insulin-regulated glucose transporter 4 (GLUT4) is expressed in human and rodent endometria. There is an inverse relationship between androgen levels and insulin-dependent glucose metabolism in women. Hyperandrogenemia, hyperinsulinemia, and insulin resistance are believed to contribute to endometrial abnormalities in women with polycystic ovary syndrome (PCOS). However, it has been unclear in previous studies if endometrial GLUT4 expression is regulated by androgen-dependent androgen receptors (ARs) and/or the insulin receptor/Akt/mTOR signaling network. In this study, we demonstrate that GLUT4 is expressed in normal endometrial cells (mainly in the epithelial cells) and is down-regulated under conditions of hyperandrogenemia in tissues from PCOS patients and in a 5α-dihydrotestosterone-induced PCOS-like rat model. Western blot analysis revealed reduced endometrial GLUT4 expression and increased AR expression in PCOS patients. However, the reduced GLUT4 level was not always associated with an increase in AR in PCOS patients when comparing non-hyperplasia with hyperplasia. Using a human tissue culture system, we investigated the molecular basis by which GLUT4 regulation in endometrial hyperplasia tissues is affected by metformin in PCOS patients. We show that specific endogenous organic cation transporter isoforms are regulated by metformin, and this suggests a direct effect of metformin on endometrial hyperplasia. Moreover, we demonstrate that metformin induces GLUT4 expression and inhibits AR expression and blocks insulin receptor/PI3K/Akt/mTOR signaling in the same hyperplasia human tissues. These findings indicate that changes in endometrial GLUT4 expression in PCOS patients involve the androgen-dependent alteration of AR expression and changes in the insulin receptor/PI3K/Akt/mTOR signaling network. PMID:26045896

  18. Reversing the reduced level of endometrial GLUT4 expression in polycystic ovary syndrome: a mechanistic study of metformin action.

    PubMed

    Li, Xin; Cui, Peng; Jiang, Hong-Yuan; Guo, Yan-Rong; Pishdari, Bano; Hu, Min; Feng, Yi; Billig, Håkan; Shao, Ruijin

    2015-01-01

    Conflicting results have been reported regarding whether or not insulin-regulated glucose transporter 4 (GLUT4) is expressed in human and rodent endometria. There is an inverse relationship between androgen levels and insulin-dependent glucose metabolism in women. Hyperandrogenemia, hyperinsulinemia, and insulin resistance are believed to contribute to endometrial abnormalities in women with polycystic ovary syndrome (PCOS). However, it has been unclear in previous studies if endometrial GLUT4 expression is regulated by androgen-dependent androgen receptors (ARs) and/or the insulin receptor/Akt/mTOR signaling network. In this study, we demonstrate that GLUT4 is expressed in normal endometrial cells (mainly in the epithelial cells) and is down-regulated under conditions of hyperandrogenemia in tissues from PCOS patients and in a 5α-dihydrotestosterone-induced PCOS-like rat model. Western blot analysis revealed reduced endometrial GLUT4 expression and increased AR expression in PCOS patients. However, the reduced GLUT4 level was not always associated with an increase in AR in PCOS patients when comparing non-hyperplasia with hyperplasia. Using a human tissue culture system, we investigated the molecular basis by which GLUT4 regulation in endometrial hyperplasia tissues is affected by metformin in PCOS patients. We show that specific endogenous organic cation transporter isoforms are regulated by metformin, and this suggests a direct effect of metformin on endometrial hyperplasia. Moreover, we demonstrate that metformin induces GLUT4 expression and inhibits AR expression and blocks insulin receptor/PI3K/Akt/mTOR signaling in the same hyperplasia human tissues. These findings indicate that changes in endometrial GLUT4 expression in PCOS patients involve the androgen-dependent alteration of AR expression and changes in the insulin receptor/PI3K/Akt/mTOR signaling network. PMID:26045896

  19. Endometrioid endometrial adenocarcinoma recurring as carcinosarcoma.

    PubMed

    Shaco-Levy, Ruthy; Piura, Benjamin

    2008-04-01

    Müllerian carcinosarcoma is currently regarded as a metaplastic (sarcomatous) carcinoma. Only five cases of pure ovarian adenocarcinoma recurring as carcinosarcoma have been documented in the literature. There are no documented cases of endometrial adenocarcinoma recurring as metaplastic carcinoma. We report of a case of endometrial adenocarcinoma, endometrioid type, recurring as metaplastic carcinoma showing sarcomatous differentiation. The tumor evolution in this case supports the prevailing opinion that Müllerian carcinosarcomas are derived from carcinomas and represent tumor progression. PMID:18412798

  20. Clinical and pathological correlations in endometrial pathology

    PubMed Central

    Bohîlțea, RE; Sajin, M; Furtunescu, F; Bohîlțea, LC; Mihart, A; Baros, A; Anca, AF

    2015-01-01

    The incidence and mortality rate of endometrial cancer has been registering an increasing trend both in Romania and in the whole world. The paper’s aim is to analyze the diagnostic approach of endometrial pathology in the University Emergency Hospital Bucharest, on a four years period. The medium age of the patients was of 50.51 ± 10.924 years, and the median age was of 48 years. The youngest patient suffering from endometrial cancer was of 30 years. Dilation and uterine curettage represent the main method used in the performance of endometrial biopsy, based on which the certitude etiologic histopathologic diagnosis was established in 68.4% of the patients with endometrial pathology. Hyperplasias represented half of the pathology (54.9%), most of them being without atypias. Endometrial carcinoma was identified in 19% of the patients. The diagnosis of the disease in IA stage represents 5.5% of the total endometrial cases and the diagnosis of the disease in the stage of its limitation to the uterus (stage IA, IB and IC) was of 64.2%. The endometrioid adenocarcinoma represents the most encountered histopathological form and the degree of tumor differentiation established for 68,15% of the cases was predominantly 1 and 2 (88%). The main symptom, which determines the patients’ decision to go to the physician, is the abnormal uterine bleeding. 66% of the cases of endometrial cancer in the stage of the disease limited to the uterus are diagnosed in Romania based on the abnormal uterine bleeding. However, 34% of the cases are diagnosed in advanced stages, presenting a significantly low life expectancy. PMID:26664489

  1. Circulating Adiponectin and Risk of Endometrial Cancer

    PubMed Central

    Zheng, Qiaoli; Wu, Haijian; Cao, Jiang

    2015-01-01

    Background Adiponectin is an insulin-sensitizing hormone produced by adipocytes. It has been suggested to be involved in endometrial tumorigenesis. Published data have shown inconsistent results for the association between circulating adiponectin levels and endometrial cancer. In this study, we conducted a meta-analysis to evaluate the predictive value of circulating adiponectin levels on the development of endometrial cancer. Methods PubMed, Embase, ISI web of knowledge, and Cochrane databases were searched for all eligible studies, and the summary relative risk (SRR) was calculated. Additionally, we performed dose-response analysis with eight eligible studies. Results A total of 1,955 cases and 3,458 controls from 12 studies were included. The SRR for the ‘highest’ vs ‘lowest’ adiponectin levels indicated high adiponectin level reduced the risk of endometrial cancer [SRR = 0.40, 95% confidence interval (CI), 0.33–0.66]. Results from the subgroup analyses were consistent with the overall analysis. The SRR for each 1 µg/ml increase of adiponectin indicated a 3% reduction in endometrial cancer risk (95% CI: 2%–4%), and a 14% reduction for each increase of 5 µg/ml (95% CI: 9%–19%). No evidence of publication bias was found. Conclusions This meta-analysis demonstrates that low level of circulating adiponectin is a risk factor for endometrial cancer. PMID:26030130

  2. Integrin αVβ3 and αVβ5 are required for leukemia inhibitory factor-mediated the adhesion of trophoblast cells to the endometrial cells.

    PubMed

    Chung, Tae-Wook; Park, Mi-Ju; Kim, Hyung Sik; Choi, Hee-Jung; Ha, Ki-Tae

    2016-01-22

    The embryo implantation including adhesion between trophoblast and endometrium is a crucial process for the successful pregnancy. LIF and adhesion molecules including integrins are known as significant factors for embryo implantation. However, the function of LIF on the regulation of adhesion molecule expression and promotion of trophoblast adhesion to endometrial cells has not been fully elucidated. Here we show that LIF significantly induced mRNA expression of ITGAV, ITGB3, and ITGB5 in endometrial cells, as evidenced by RT-PCR and qRT-PCR analysis. Based on the results from treatment of antagonist for LIF receptor (hLA), LIF positively regulates expression of integrin αV, β3, and β5, and adhesion of the human trophectoderm-derived JAr cells to endometrial Ishikawa cells. Furthermore, the adhesion between trophoblastic cells and LIF-stimulated endometrial cells was significantly reduced by neutralization of LIF-mediated integrin β3 and β5 expression on endometrial cell surface with integrin subunit β3 and β5 antibodies. Taken together, we firstly demonstrate that LIF enhances the adhesion of trophoblastic cells to endometrial cells by up-regulating expression of integrin heterodimer αVβ3 and αVβ5, indicating the promotion of endometrial receptivity for embryo implantation. PMID:26723254

  3. Endoplasmic Reticulum Stress in Endometrial Cancer

    PubMed Central

    Ulianich, Luca; Insabato, Luigi

    2014-01-01

    Endometrial cancer (EC) is a common gynecologic malignancy often diagnosed at early stage. In spite of a huge advance in our understanding of EC biology, therapeutic modalities do not have significantly changed over the past 40 years. A restricted number of genes have been reported to be mutated in EC, mediating cell proliferation and invasiveness. However, besides these alterations, few other groups and ourselves recently identified the activation of the unfolded protein response (UPR) and GRP78 increase following endoplasmic reticulum (ER) stress as mechanisms favoring growth and invasion of EC cells. Here, a concise update on currently available data in the field is presented, analyzing the crosstalk between the UPR and the main signaling pathways regulating EC cell proliferation and survival. It is evident that this is a rapidly expanding and promising issue. However, more data are very likely to yield a better understanding on the mechanisms through which EC cells can survive the low oxygen and glucose tumor microenvironment. In this perspective, the UPR and, particularly, GRP78 might constitute a novel target for the treatment of EC in combination with traditional adjuvant therapy. PMID:25593927

  4. Endometrial carcinoma in elderly women.

    PubMed

    Hoffman, K; Nekhlyudov, L; Deligdisch, L

    1995-08-01

    Endometrial carcinoma remains the most common invasive gynecologic malignancy. Increased longevity is associated with an increased incidence of endometrial carcinoma (EC) in elderly women. While recent studies have looked at aging and its relation to ovarian, breast, and cervical cancer, few have focused on EC in the growing elderly population. This study analyzed 35 histologic specimens of EC in women 75-92 years of age. Findings revealed that only 23% of the tumors were Stage I, G1. The majority (77%) were deeply invasive or of advanced stage (IC-IV). These were G2, G3, or "virulent" types of nonendometrioid EC (undifferentiated, clear cell, uterine serous papillary, and squamous cell carcinoma). Fifty-seven percent of tumors were endometrioid, of which 9% were mixed, including a rare case of nongestational choriocarcinoma. The nonendometrioid tumors, compared to the endometrioid types, were more often high-stage tumors with vascular invasion. They were also more often associated with atrophic (vs hyperplastic) uninvolved endometrium. Clinical risk factors (nulliparity, obesity, estrogen replacement therapy) were assessed and correlated with the histologic findings. It was shown that tumors in the elderly were less likely to be estrogen-related. It was concluded that EC in this age group is more aggressive, histologically less differentiated, and often nonendometrioid compared with EC in the general population. The increased virulence of EC in the elderly may be related to the tumor's independence from hormonal factors, to the poorly understood but well-known diminished immunologic defense against cancer in general in elderly patients, and/or to the belated diagnosis of the disease in this population. PMID:7622105

  5. Historical Text Comprehension Reflective Tutorial Dialogue System

    ERIC Educational Resources Information Center

    Grigoriadou, Maria; Tsaganou, Grammatiki; Cavoura, Theodora

    2005-01-01

    The Reflective Tutorial Dialogue System (ReTuDiS) is a system for learner modelling historical text comprehension through reflective dialogue. The system infers learners' cognitive profiles and constructs their learner models. Based on the learner model the system plans the appropriate--personalized for learners--reflective tutorial dialogue in…

  6. Granulocyte-Colony Stimulating Factor Related Pathways Tested on an Endometrial Ex-Vivo Model

    PubMed Central

    Rahmati, Mona; Petitbarat, Marie; Dubanchet, Sylvie; Bensussan, Armand; Chaouat, Gerard; Ledee, Nathalie

    2014-01-01

    Introduction Recombinant human Granulocyte-Colony Stimulating Factor (rhG-CSF) supplementation seems to be a promising innovative therapy in reproductive medicine, used in case of recurrent miscarriage, embryo implantation failure or thin endometrium, although its mechanisms of action remain unknown. Our aim was to identify possible endometrial pathways influenced by rhG-CSF. Materials and Methods Hypothetical molecular interactions regulated by G-CSF were designed through a previous large scale endometrial microarray study. The variation of endometrial expression of selected target genes was confirmed in control and infertile patients. G-CSF supplementation influence on these targets was tested on an endometrial ex-vivo culture. Middle luteal phase endometrial biopsies were cultured on collagen sponge with or without rhG-CSF supplementation during 3 consecutive days. Variations of endometrial mRNA expression for the selected targets were studied by RT-PCR. Results At the highest dose of rhG-CSF stimulation, the mRNA expression of these selected target genes was significantly increased if compared with their expression without addition of rhG-CSF. The selected targets were G-CSF Receptor (G-CSFR), Integrin alpha-V/beta-3 (ITGB3) implicated in cell migration and embryo implantation, Plasminogen Activator Urokinase Receptor (PLAUR) described as interacting with integrins and implicated in cell migration, Thymidine Phosphorylase (TYMP) implicated in local angiogenesis, CD40 and its ligand CD40L involved in cell proliferation control. Conclusion RhG-CSF seems able to influence endometrial expressions crucial for implantation process involving endometrial vascular remodelling, local immune modulation and cellular adhesion pathways. These variations observed in an ex-vivo model should be tested in-vivo. The strict indications or counter indication of rhG-CSF supplementation in reproductive field are not yet established, while the safety of its administration in early

  7. The Play of Socratic Dialogue

    ERIC Educational Resources Information Center

    Smith, Richard

    2011-01-01

    Proponents of philosophy for children generally see themselves as heirs to the "Socratic" tradition. They often claim too that children's aptitude for play leads them naturally to play with abstract, philosophical ideas. However in Plato's dialogues we find in the mouth of "Socrates" many warnings against philosophising with the young. Those…

  8. Facilitating Dialogues about Racial Realities

    ERIC Educational Resources Information Center

    Quaye, Stephen John

    2014-01-01

    Background/Context: Facilitating dialogues about racial issues in higher education classroom settings continues to be a vexing problem facing postsecondary educators. In order for students to discuss race with their peers, they need skilled facilitators who are knowledgeable about racial issues and able to support students in these difficult…

  9. Virtual Worlds and Course Dialogue

    ERIC Educational Resources Information Center

    Tapsis, Nikolaos; Tsolakidis, Konstantinos; Vitsilaki, Chryssi

    2012-01-01

    This study explores the effects of the use of Second Life (SL) as a learning environment on a course's dialogue. An experimental design within groups was used with thirty-seven graduate students for three weeks. Half of them followed the course activities in the official Learning Management System (LMS) of the program, Blackboard Vista, and the…

  10. The Production of Interleukin-11 and Decidualization Are Compromised in Endometrial Stromal Cells Derived from Patients with Infertility

    PubMed Central

    Karpovich, Natalia; Klemmt, Petra; McVeigh, J. Enda; Barlow, David H.; Mardon, Helen J.; Hwang, Jung Hye; Heath, John K.

    2006-01-01

    IL-11 signaling is critical for decidualization of the endometrial stroma in early pregnancy in the mouse. In this study, we investigate the function of IL-11 signaling in cAMP-induced decidualization of human endometrial stromal cells. We show that treatment of endometrial stromal cells with 8-bromo-cAMP (8-Br-cAMP) results in an increase in the levels of secreted IL-11, whereas levels of cell surface IL-11 receptor α are similar with or without 8-Br-cAMP treatment. The production of IL-11 correlates with the production of molecular markers of decidualization, prolactin and IGF-binding protein-1. The expression of these markers is inhibited when IL-11 signaling is specifically blocked in decidualizing endometrial stromal cells by the IL-11 antagonist W147A. We demonstrate that 8-Br-cAMP-induced endometrial stromal cells derived from patients with primary infertility produce lower levels of prolactin, IGF-binding protein-1, and IL-11 than cells derived from fertile women. Our results suggest that IL-11 expression is critically important during decidualization in the human endometrium, and that aberrant regulation of endometrial IL-11 production may be associated with some types of infertility. PMID:15613426

  11. A Common Variant at the 14q32 Endometrial Cancer Risk Locus Activates AKT1 through YY1 Binding.

    PubMed

    Painter, Jodie N; Kaufmann, Susanne; O'Mara, Tracy A; Hillman, Kristine M; Sivakumaran, Haran; Darabi, Hatef; Cheng, Timothy H T; Pearson, John; Kazakoff, Stephen; Waddell, Nicola; Hoivik, Erling A; Goode, Ellen L; Scott, Rodney J; Tomlinson, Ian; Dunning, Alison M; Easton, Douglas F; French, Juliet D; Salvesen, Helga B; Pollock, Pamela M; Thompson, Deborah J; Spurdle, Amanda B; Edwards, Stacey L

    2016-06-01

    A recent meta-analysis of multiple genome-wide association and follow-up endometrial cancer case-control datasets identified a novel genetic risk locus for this disease at chromosome 14q32.33. To prioritize the functional SNP(s) and target gene(s) at this locus, we employed an in silico fine-mapping approach using genotyped and imputed SNP data for 6,608 endometrial cancer cases and 37,925 controls of European ancestry. Association and functional analyses provide evidence that the best candidate causal SNP is rs2494737. Multiple experimental analyses show that SNP rs2494737 maps to a silencer element located within AKT1, a member of the PI3K/AKT/MTOR intracellular signaling pathway activated in endometrial tumors. The rs2494737 risk A allele creates a YY1 transcription factor-binding site and abrogates the silencer activity in luciferase assays, an effect mimicked by transfection of YY1 siRNA. Our findings suggest YY1 is a positive regulator of AKT1, mediating the stimulatory effects of rs2494737 increasing endometrial cancer risk. Identification of an endometrial cancer risk allele within a member of the PI3K/AKT signaling pathway, more commonly activated in tumors by somatic alterations, raises the possibility that well tolerated inhibitors targeting this pathway could be candidates for evaluation as chemopreventive agents in individuals at high risk of developing endometrial cancer. PMID:27259051

  12. Mechanism of progestin resistance in endometrial precancer/cancer through Nrf2-AKR1C1 pathway

    PubMed Central

    Wang, Yiying; Wang, Yue; Zhang, Zhenbo; Park, Ji-Young; Guo, Donghui; Liao, Hong; Yi, Xiaofang; Zheng, Yu; Zhang, Donna; Chambers, Setsuko K.; Zheng, Wenxin

    2016-01-01

    Progestin resistance is a main obstacle for endometrial precancer/cancer conservative therapy. Therefore, biomarkers to predict progestin resistance and studies to gain a more detailed understanding of the mechanism are needed. The antioxidant Nrf2-AKR1C1 signal pathway exerts chemopreventive activity. However whether it plays a role in progestin resistance has not been explored. In this study, elevated levels of AKR1C1 and Nrf2 were found in progestin-resistant endometrial epithelia, but not in responsive endometrial glands. Exogenous overexpression of Nrf2/AKR1C1 resulted in progestin resistance. Inversely, silencing of Nrf2 or AKR1C1 rendered endometrial cancer cells more susceptible to progestin treatment. Moreover, medroxyprogesterone acetate withdrawal resulted in suppression of Nrf2/AKR1C1 expression accompanied by a reduction of cellular proliferative activity. In addition, brusatol and metformin overcame progestin resistance by down-regulating Nrf2/AKR1C1 expression. Our findings suggest that overexpression of Nrf2 and AKR1C1 in endometrial precancer/cancer may be part of the molecular mechanisms underlying progestin resistance. If validated in a larger cohort, overexpression of Nrf2 and AKR1C1 may prove to be useful biomarkers to predict progestin resistance. Targeting the Nrf2/AKR1C1 pathway may represent a new therapeutic strategy for treatment of endometrial hyperplasia/cancer. PMID:26824415

  13. Interleukin 6 promotes endometrial cancer growth through an autocrine feedback loop involving ERK-NF-κB signaling pathway.

    PubMed

    Che, Qi; Liu, Bin-Ya; Wang, Fang-Yuan; He, Yin-Yan; Lu, Wen; Liao, Yun; Gu, Wei; Wan, Xiao-Ping

    2014-03-28

    Interleukin (IL)-6 as an inflammation factor, has been proved to promote cancer proliferation in several human cancers. However, its role in endometrial cancer has not been studied clearly. Previously, we demonstrated that IL-6 promoted endometrial cancer progression through local estrogen biosynthesis. In this study, we proved that IL-6 could directly stimulate endometrial cancer cells proliferation and an autocrine feedback loop increased its production even after the withdrawal of IL-6 from the medium. Next, we analyzed the mechanism underlying IL-6 production in the feedback loop and found that its production and IL-6-stimulated cell proliferation were effectively blocked by pharmacologic inhibitors of nuclear factor-kappa B (NF-κB) and extra-cellular signal-regulated kinase (ERK). Importantly, activation of ERK was upstream of the NF-κB pathways, revealing the hierarchy of this event. Finally, we used an orthotopic nude endometrial carcinoma model to confirm the effects of IL-6 on the tumor progression. Taken together, these data indicate that IL-6 promotes endometrial carcinoma growth through an expanded autocrine regulatory loop and implicate the ERK-NF-κB pathway as a critical mediator of IL-6 production, implying IL-6 to be an important therapeutic target in endometrial carcinoma. PMID:24582558

  14. Mechanism of progestin resistance in endometrial precancer/cancer through Nrf2-AKR1C1 pathway.

    PubMed

    Wang, Yiying; Wang, Yue; Zhang, Zhenbo; Park, Ji-Young; Guo, Donghui; Liao, Hong; Yi, Xiaofang; Zheng, Yu; Zhang, Donna; Chambers, Setsuko K; Zheng, Wenxin

    2016-03-01

    Progestin resistance is a main obstacle for endometrial precancer/cancer conservative therapy. Therefore, biomarkers to predict progestin resistance and studies to gain a more detailed understanding of the mechanism are needed. The antioxidant Nrf2-AKR1C1 signal pathway exerts chemopreventive activity. However whether it plays a role in progestin resistance has not been explored. In this study, elevated levels of AKR1C1 and Nrf2 were found in progestin-resistant endometrial epithelia, but not in responsive endometrial glands. Exogenous overexpression of Nrf2/AKR1C1 resulted in progestin resistance. Inversely, silencing of Nrf2 or AKR1C1 rendered endometrial cancer cells more susceptible to progestin treatment. Moreover, medroxyprogesterone acetate withdrawal resulted in suppression of Nrf2/AKR1C1 expression accompanied by a reduction of cellular proliferative activity. In addition, brusatol and metformin overcame progestin resistance by down-regulating Nrf2/AKR1C1 expression. Our findings suggest that overexpression of Nrf2 and AKR1C1 in endometrial precancer/cancer may be part of the molecular mechanisms underlying progestin resistance. If validated in a larger cohort, overexpression of Nrf2 and AKR1C1 may prove to be useful biomarkers to predict progestin resistance. Targeting the Nrf2/AKR1C1 pathway may represent a new therapeutic strategy for treatment of endometrial hyperplasia/cancer. PMID:26824415

  15. Synergism between PGC-1α and estrogen in the survival of endometrial cancer cells via the mitochondrial pathway

    PubMed Central

    Yang, Hui; Yang, Rui; Liu, Hao; Ren, Zhongqian; Kong, Fanfei; Li, Da; Ma, Xiaoxin

    2016-01-01

    Accumulating evidence shows that peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) is involved in the progression of hormone-related cancers, and there may exist an association between estrogen and PGC-1α. Notably, emerging evidence has led to considerable interest in the role of PGC-1α in endometrial cancer development. However, whether the synergism exists between PGC-1α and estrogen for regulating mitochondrial function to promote the development of endometrial cancer remains largely unknown. Here, we show that: 1) knockdown of PGC-1α attenuates the survival of endometrial cancer cells by inducing cell apoptosis through the mitochondrial pathway; 2) estrogen remedies the PGC-1α efficiency-induced decline of endometrial cancer cell viability; and 3) estrogen modulates the mitochondrial function to inhibit the PGC-1α deficiency-induced apoptosis in endometrial cancer cells. Collectively, these results demonstrated that the synergism between PGC-1α and estrogen was required for the survival of endometrial cancer cells, which was dependent on the mitochondrial pathway. PMID:27418839

  16. Hormonal, metabolic, and inflammatory profiles and endometrial cancer risk within the EPIC cohort--a factor analysis.

    PubMed

    Dossus, Laure; Lukanova, Annekatrin; Rinaldi, Sabina; Allen, Naomi; Cust, Anne E; Becker, Susen; Tjonneland, Anne; Hansen, Louise; Overvad, Kim; Chabbert-Buffet, Nathalie; Mesrine, Sylvie; Clavel-Chapelon, Francoise; Teucher, Birgit; Chang-Claude, Jenny; Boeing, Heiner; Drogan, Dagmar; Trichopoulou, Antonia; Benetou, Vasiliki; Bamia, Christina; Palli, Domenico; Agnoli, Claudia; Galasso, Rocco; Tumino, Rosario; Sacerdote, Carlotta; Bueno-de-Mesquita, H Bas; van Duijnhoven, Fränzel J B; Peeters, Petra H M; Onland-Moret, N Charlotte; Redondo, Maria-Luisa; Travier, Noémie; Sanchez, Maria-Jose; Altzibar, Jone M; Chirlaque, Maria-Dolores; Barricarte, Aurelio; Lundin, Eva; Khaw, Kay-Tee; Wareham, Nicholas; Fedirko, Veronika; Romieu, Isabelle; Romaguera, Dora; Norat, Teresa; Riboli, Elio; Kaaks, Rudolf

    2013-04-15

    A "Western" lifestyle characterized by physical inactivity and excess weight is associated with a number of metabolic and hormonal dysregulations, including increased circulating estrogen levels, hyperinsulinemia, hyperglycemia, and chronic inflammation. The same hormonal and metabolic axes might mediate the association between this lifestyle and the development of endometrial cancer. Using data collected within the European Prospective Investigation into Cancer and Nutrition (EPIC), a prospective cohort study carried out in 10 European countries during 1992-2000, we conducted a factor analysis to delineate important components that summarize the variation explained by a set of biomarkers and to examine their association with endometrial cancer risk. Prediagnostic levels of testosterone, androstenedione, dehydroepiandrosterone sulfate, sex hormone-binding globulin, estrone, estradiol, C-peptide, insulin-like growth factor-binding proteins 1 and 2, adiponectin, high- and low-density lipoprotein cholesterol, glucose, triglycerides, tumor necrosis factor (TNF) α, soluble TNF receptors 1 and 2, C-reactive protein, interleukin-6, and interleukin-1 receptor antagonist were measured in 233 incident endometrial cancer cases and 446 matched controls. Factor analysis identified 3 components associated with postmenopausal endometrial cancer risk that could be labeled "insulin resistance/metabolic syndrome," "steroids," and "inflammation" factors. A fourth component, "lipids," was not significantly associated with endometrial cancer. In conclusion, besides the well-known associations of risk with sex hormones and insulin-regulated physiological axes, our data further support the hypothesis that inflammation factors play a role in endometrial carcinogenesis. PMID:23492765

  17. Study establishes basis for genomic classification of endometrial cancers

    Cancer.gov

    A comprehensive genomic analysis of nearly 400 endometrial tumors suggests that certain molecular characteristics – such as the frequency of mutations – could complement current pathology methods and help distinguish between principal types of endometrial

  18. Interleukin 6 promotes endometrial cancer growth through an autocrine feedback loop involving ERK–NF-κB signaling pathway

    SciTech Connect

    Che, Qi; Liu, Bin-Ya; Wang, Fang-Yuan; He, Yin-Yan; Lu, Wen; Liao, Yun; Gu, Wei; Wan, Xiao-Ping

    2014-03-28

    Highlights: • IL-6 could promote endometrial cancer cells proliferation. • IL-6 promotes its own production through an autocrine feedback loop. • ERK and NF-κB pathway inhibitors inhibit IL-6 production and tumor growth. • IL-6 secretion relies on the activation of ERK–NF-κB pathway axis. • An orthotopic nude endometrial carcinoma model confirms the effect of IL-6. - Abstract: Interleukin (IL)-6 as an inflammation factor, has been proved to promote cancer proliferation in several human cancers. However, its role in endometrial cancer has not been studied clearly. Previously, we demonstrated that IL-6 promoted endometrial cancer progression through local estrogen biosynthesis. In this study, we proved that IL-6 could directly stimulate endometrial cancer cells proliferation and an autocrine feedback loop increased its production even after the withdrawal of IL-6 from the medium. Next, we analyzed the mechanism underlying IL-6 production in the feedback loop and found that its production and IL-6-stimulated cell proliferation were effectively blocked by pharmacologic inhibitors of nuclear factor-kappa B (NF-κB) and extra-cellular signal-regulated kinase (ERK). Importantly, activation of ERK was upstream of the NF-κB pathways, revealing the hierarchy of this event. Finally, we used an orthotopic nude endometrial carcinoma model to confirm the effects of IL-6 on the tumor progression. Taken together, these data indicate that IL-6 promotes endometrial carcinoma growth through an expanded autocrine regulatory loop and implicate the ERK–NF-κB pathway as a critical mediator of IL-6 production, implying IL-6 to be an important therapeutic target in endometrial carcinoma.

  19. Whole-exome sequencing combined with functional genomics reveals novel candidate driver cancer genes in endometrial cancer.

    PubMed

    Liang, Han; Cheung, Lydia W T; Li, Jie; Ju, Zhenlin; Yu, Shuangxing; Stemke-Hale, Katherine; Dogruluk, Turgut; Lu, Yiling; Liu, Xiuping; Gu, Chao; Guo, Wei; Scherer, Steven E; Carter, Hannah; Westin, Shannon N; Dyer, Mary D; Verhaak, Roeland G W; Zhang, Fan; Karchin, Rachel; Liu, Chang-Gong; Lu, Karen H; Broaddus, Russell R; Scott, Kenneth L; Hennessy, Bryan T; Mills, Gordon B

    2012-11-01

    Endometrial cancer is the most common gynecological malignancy, with more than 280,000 cases occurring annually worldwide. Although previous studies have identified important common somatic mutations in endometrial cancer, they have primarily focused on a small set of known cancer genes and have thus provided a limited view of the molecular basis underlying this disease. Here we have developed an integrated systems-biology approach to identifying novel cancer genes contributing to endometrial tumorigenesis. We first performed whole-exome sequencing on 13 endometrial cancers and matched normal samples, systematically identifying somatic alterations with high precision and sensitivity. We then combined bioinformatics prioritization with high-throughput screening (including both shRNA-mediated knockdown and expression of wild-type and mutant constructs) in a highly sensitive cell viability assay. Our results revealed 12 potential driver cancer genes including 10 tumor-suppressor candidates (ARID1A, INHBA, KMO, TTLL5, GRM8, IGFBP3, AKTIP, PHKA2, TRPS1, and WNT11) and two oncogene candidates (ERBB3 and RPS6KC1). The results in the "sensor" cell line were recapitulated by siRNA-mediated knockdown in endometrial cancer cell lines. Focusing on ARID1A, we integrated mutation profiles with functional proteomics in 222 endometrial cancer samples, demonstrating that ARID1A mutations frequently co-occur with mutations in the phosphatidylinositol 3-kinase (PI3K) pathway and are associated with PI3K pathway activation. siRNA knockdown in endometrial cancer cell lines increased AKT phosphorylation supporting ARID1A as a novel regulator of PI3K pathway activity. Our study presents the first unbiased view of somatic coding mutations in endometrial cancer and provides functional evidence for diverse driver genes and mutations in this disease. PMID:23028188

  20. Mechanisms of Normal and Abnormal Endometrial Bleeding

    PubMed Central

    Lockwood, Charles J.

    2011-01-01

    Expression of tissue factor (TF), the primary initiator of coagulation, is enhanced in decidualized human endometrial stromal cells (HESC) during the progesterone-dominated luteal phase. Progesterone also augments a second HESC hemostatic factor, plasminogen activator inhibitor-1 (PAI-1). In contrast, progestins inhibit HESC matrix metalloproteinase (MMP)-1, 3 and 9 expression to stabilize endometrial stromal and vascular extracellular matrix. Through these mechanisms decidualized endometrium is rendered both hemostatic and resistant to excess trophoblast invasion in the mid-luteal phase and throughout gestation to prevent hemorrhage and accreta. In non-fertile cycles, progesterone withdrawal results in decreased HESC TF and PAI-expression and increased MMP activity and inflammatory cytokine production promoting the controlled hemorrhage of menstruation and related tissue sloughing. In contrast to these well ordered biochemical processes, unpredictable endometrial bleeding associated with anovulation reflects absence of progestational effects on TF, PAI-1 and MMP activity as well as unrestrained angiogenesis rendering the endometrium non-hemostatic, proteolytic and highly vascular. Abnormal bleeding associated with long-term progestin-only contraceptives results not from impaired hemostasis but from unrestrained angiogenesis leading to large fragile endometrial vessels. This abnormal angiogenesis reflects progestational inhibition of endometrial blood flow promoting local hypoxia and generation of reactive oxygen species that increase production of angiogenic factors such as vascular endothelial growth factor (VEGF) in HESCs and Angiopoietin-2 (Ang-2) in endometrial endothelial cells while decreasing HESC expression of angiostatic, Ang-1. The resulting vessel fragility promotes bleeding. Aberrant angiogenesis also underlies abnormal bleeding associated with myomas and endometrial polyps however there are gaps in our understanding of this pathology. PMID:21499503

  1. Quantitative PCR marker genes for endometrial adenocarcinoma.

    PubMed

    Kölbl, Alexandra C; Victor, Lisa-Marie; Birk, Amelie E; Jeschke, Udo; Andergassen, Ulrich

    2016-09-01

    Endometrial adenocarcinoma is a common malignancy in women worldwide, with formation of remote metastasis occurring following oncological treatment. Circulating tumor cells (CTCs) are regarded to be the origin of haematogenous metastasis formation. The present study aimed to identify suitable marker genes using a quantitative polymerase chain reaction (qPCR) approach to detect CTCs from blood samples of patients with endometrial carcinoma. Therefore, RNA was isolated from endometrial adenocarcinoma cell lines and from healthy endometrial tissue and reverse transcribed to cDNA, which was then used in qPCR on a number of marker genes. Cytokeratin 19 and claudin 4 were identified as suitable marker genes for CTCs in endometrial adenocarcinoma, due to their high expression in the majority of the cell lines investigated. The expression values of the genes examined varied widely between the different cell lines, which is similar to the variation in the patient samples. Therefore, the necessity for a set of genes for CTC detection and not one single marker gene is demonstrated. qPCR is a fast, cost‑efficient and easy to perform technique, which may be used in the detection of CTCs. Investigation of the occurrence of CTCs in cancer patients would aid in the prevention of metastasis and thereby refine treatment. PMID:27431566

  2. Endometrial LGR7 expression and implantation failure.

    PubMed

    Campitiello, Maria Rosaria; Caprio, Francesca; Mele, Daniela; D'eufemia, Diletta; Colacurci, Nicola; De Franciscis, Pasquale

    2016-06-01

    Implantation failure is considered as a major cause of infertility in women with recurrent pregnancy loss (RPL) and in otherwise healthy women with unexplained infertility. Preliminary data in primates suggested that relaxin (RLX) is involved in endometrial preparation for implantation. In a prospective observational study, the endometrial RLX receptor (LGR7) expression was assessed in three groups of patients with regular ovulatory cycle and normal uterine cavity: 23 with RPL (Group A), 23 with unexplained infertility undergone at least three cycles of failed in vitro fertilization (IVF) reporting good oocyte and embryo quality (Group B), 23 with proven fertility (Group C). Assessment of LGR7 expression was performed with both polymerase chain reaction (PCR) analysis and immunohistochemistry on endometrial samples obtained with hysteroscopic biopsy performed in the secretory phase of the menstrual cycle. Endometrial LGR7 was less expressed in group A and B versus C, both by PCR analysis (p = 0.024) and immunohistochemistry. The decreased expression of the endometrial RLX receptor in women with implantation failures, both in vitro fertilization failure and recurrent pregnancy loss, suggests that RLX may play a crucial role in the structural and functional changes of the endometrium during the window of implantation. PMID:26761440

  3. Protein Kinase C alpha (PKCα) dependent signaling mediates endometrial cancer cell growth and tumorigenesis

    PubMed Central

    Haughian, James M.; Reno, Elaine M.; Thorne, Alicia M.; Bradford, Andrew P.

    2009-01-01

    Endometrial cancer is the most common invasive gynecologic malignancy, yet molecular mechanisms and signaling pathways underlying its etiology and pathophysiology remain poorly characterized. We sought to define a functional role for the protein kinase C (PKC) isoform, PKCα, in an established cell model of endometrial adenocarcinoma. Ishikawa cells depleted of PKCα protein grew slower, formed fewer colonies in anchorage-independent growth assays and exhibited impaired xenograft tumor formation in nude mice. Consistent with impaired growth, PKCα knockdown increased levels of the cyclin dependent kinase (CDK) inhibitors p21Cip1/WAF1 (p21) and p27Kip1 (p27). Despite the absence of functional phosphatase and tensin homologue (PTEN) protein in Ishikawa cells, PKCα knockdown reduced Akt phosphorylation at serine 473 and concomitantly inhibited phosphorylation of the Akt target, glycogen synthase kinase-3β (GSK-3β). PKCα knockdown also resulted in decreased basal ERK phosphorylation and attenuated ERK activation following EGF stimulation. p21 and p27 expression was not increased by treatment of Ishikawa cells with ERK and Akt inhibitors, suggesting PKCα regulates CDK expression independently of Akt and ERK. Immunohistochemical analysis of grade 1 endometrioid adenocarcinoma revealed aberrant PKCα expression, with foci of elevated PKCα staining, not observed in normal endometrium. These studies demonstrate a critical role for PKCα signaling in endometrial tumorigenesis by regulating expression of CDK inhibitors p21 and p27 and activation of Akt and ERK dependent proliferative pathways. Thus, targeting PKCα may provide novel therapeutic options in endometrial tumors. PMID:19672862

  4. Delineating the prime mover action of progesterone for endometrial receptivity in primates

    PubMed Central

    Ghosh, D.; Sengupta, J.

    2014-01-01

    Progesterone is essential for endometrial receptivity in primates. It is now evident that embryo-derived signal influences implantation stage endometrium under progesterone dominance, and collectively results in endometrial receptivity to implanting blastocyst. Previously, a few studies were performed using global gene profiling based on microarray technology to identify changes in gene expression between early luteal phase and mid luteal phase endometrium, however, the issue of combinatorial regulation by progesterone-dependent regulation and by embryo-derived signal on transcripts profiles during endometrial differentiation toward receptivity for blastocyst implantation in primates has not been addressed. The present review summarizes a few issues, specifically that of transforming growth factor β-tumour necrosis factor α (TGFβ-TNFα) pathways and signal transducer and activator of transcription (STAT) signalling system related to luteal phase progesterone action on endometrial receptivity in terms of its transcriptomic expression using a potent antiprogestin (mifepristone) in conception cycles of the rhesus monkey as a non-human primate model. PMID:25673534

  5. MiR-218 inhibits HMGB1-mediated autophagy in endometrial carcinoma cells during chemotherapy

    PubMed Central

    Ran, Xiaomin; Yang, Juan; Liu, Chaoxia; Zhou, Ping; Xiao, Linzhi; Zhang, Keqiang

    2015-01-01

    Endometrial carcinoma is the most common gynecological malignancy among women worldwide. Although treatment for EC has improved with the introduction of Paclitaxel (Tax) chemotherapy, the majority of patients will develop resistance to the treatment, leading to poor prognosis. One of the causes of chemoresistance is the increased ability to undergo autophagy. In this study, we identified that miR-218 was significantly down-regulated in Tax-resistant EC cells compared to the non-drug resistant cell lines, and overexpression of miR-218 sensitized paclitaxel resistant EC cells to paclitaxel. Moreover, we demonstrated that miR-218 directly binds to the 3’-UTR of HMGB1 gene. HMGB1 was upregulated in paclitaxel resistant EC cells, it mediated autophagy and contributed to chemotherapy resistance in endometrial carcinoma in vitro. HMGB1-mediated autophagy could be suppressed by miR-218 overexpression in Tax resistant EC cells. In summary, we determined the targeting role of miR-218 to HMGB1 and the regulation of miR-218 on the HMGB1-mediated cell autophagy during chemotherapy resistance in endometrial carcinoma cells. These results reveal novel potential role of miR-218 against chemotherapy resistance during the treatment of endometrial carcinoma. PMID:26261543

  6. Figure analysis: An implementation dialogue.

    PubMed

    Wiles, Amy M

    2016-07-01

    Figure analysis is a novel active learning teaching technique that reinforces visual literacy. Small groups of students discuss diagrams in class in order to learn content. The instructor then gives a brief introduction and later summarizes the content of the figure. This teaching technique can be used in place of lecture as a mechanism to deliver information to students. Here, a "how to" guide is presented in the form of an in-class dialogue, displaying the difficulties in visual interpretation that some students may experience while figure analysis is being implemented in an upper-level, cell biology course. Additionally, the dialogue serves as a guide for instructors who may implement the active learning technique as they consider how to respond to students' concerns in class. © 2016 by The International Union of Biochemistry and Molecular Biology, 44(4):345-348, 2016. PMID:26892173

  7. Characterization of endometrial mesenchymal stem-like cells obtained by endometrial biopsy during routine diagnostics.

    PubMed

    Schüring, Andreas N; Schulte, Nicole; Kelsch, Reinhard; Röpke, Albrecht; Kiesel, Ludwig; Götte, Martin

    2011-01-01

    Endometrial cell clones derived from in vitro cultured purified stromal cells obtained by endometrial biopsy display characteristic stem cell features, including clonality; long-term culturing properties; multilineage differentiation potential; expression of CD146, CD105, CD90, CD73, MSI1, NOTCH1, and SOX2; and absence of CD34 and CD14 expression. We conclude that adult stem cells are present in endometrial biopsies performed in a routine clinical setting, offering new large-scale approaches for future research, diagnostics, and therapies involving adult stem cells. PMID:20864098

  8. Uterine endometrial polyp with severe hemorrhage and cystic endometrial hyperplasia-pyometra complex in a dog.

    PubMed

    Gumber, Sanjeev; Springer, Nora; Wakamatsu, Nobuko

    2010-05-01

    The current report describes an unusual presentation of uterine endometrial polyp with severe hemorrhage and cystic endometrial hyperplasia-pyometra complex in a 9.5-year-old female Doberman Pinscher. The dog presented with a 2-day history of bloody discharge from the vulva and an enlarged abdomen. The postmortem examination revealed a markedly distended right uterine horn with a large pedunculated mass (17 cm x 9 cm x 4 cm) and blood. Based on the histological findings, the diagnosis of uterine endometrial polyp was made. PMID:20453227

  9. Endometrial Stromal Nodule: Report of a Case

    PubMed Central

    Fdili Alaoui, F. Z.; Chaara, H.; Bouguern, H.; Melhouf, M. A.; Fatemi, H.; Belmlih, A.; Amarti, A.

    2011-01-01

    Endometrial stromal nodule (ESN) is the least common of the endometrial stromal tumors. They are rare neoplasms which are diagnosed in most instances by light microscopy. Although such nodules are benign, hysterectomy has been considered the treatment of choice to determine the margins of the tumor required for diagnosis and to differentiate it from invasive stromal sarcoma Whose prognosis is totally different. We report a case of a 45 years old woman, with presurgical diagnosis of adnexal mass or uterine tumor. She underwent a total abdominal hysterectomy. Pathologic examination revealed an endometrial stromal nodule. Through this observation, we insist on the fact that the ESNs are rare and benign entities which must be differentiated from the other invasive malignant stromal tumors; this can change the final prognosis. PMID:21423543

  10. Endometrial stromal nodule: report of a case.

    PubMed

    Fdili Alaoui, F Z; Chaara, H; Bouguern, H; Melhouf, M A; Fatemi, H; Belmlih, A; Amarti, A

    2011-01-01

    Endometrial stromal nodule (ESN) is the least common of the endometrial stromal tumors. They are rare neoplasms which are diagnosed in most instances by light microscopy. Although such nodules are benign, hysterectomy has been considered the treatment of choice to determine the margins of the tumor required for diagnosis and to differentiate it from invasive stromal sarcoma Whose prognosis is totally different. We report a case of a 45 years old woman, with presurgical diagnosis of adnexal mass or uterine tumor. She underwent a total abdominal hysterectomy. Pathologic examination revealed an endometrial stromal nodule. Through this observation, we insist on the fact that the ESNs are rare and benign entities which must be differentiated from the other invasive malignant stromal tumors; this can change the final prognosis. PMID:21423543

  11. Metformin for endometrial hyperplasia: a Cochrane protocol

    PubMed Central

    Clement, Naomi S; Oliver, Thomas R W; Shiwani, Hunain; Saner, Juliane R F; Mulvaney, Caroline A; Atiomo, William

    2016-01-01

    Introduction Endometrial hyperplasia is a precancerous lesion of the endometrium, commonly presenting with uterine bleeding. If managed expectantly, it frequently progresses to endometrial carcinoma, rates of which are increasing dramatically worldwide. However, the established treatment for endometrial hyperplasia (progestogens) involves multiple side effects and leaves the risk of recurrence. Metformin is the most commonly used oral hypoglycaemic agent in type 2 diabetes mellitus. It has also been linked to the reversal of endometrial hyperplasia and may therefore contribute to decreasing the prevalence of endometrial carcinoma without the fertility and side effect consequences of current therapies. However, the efficacy and safety of metformin being used for this therapeutic target is unclear and, therefore, this systematic review will aim to determine this. Methods and analysis We will search the following trials and databases with no language restrictions: Cochrane Gynaecology and Fertility Specialised Register; Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; EMBASE; EBSCO Cumulative Index to Nursing and Allied Health Literature; PubMed; Google Scholar; ClinicalTrials.gov; the WHO International Trials Registry Platform portal; OpenGrey and the Latin American and Caribbean Health Sciences Literature (LILACS). We will include randomised controlled trials (RCTs) of use of metformin compared with a placebo or no treatment, conventional medical treatment (eg, progestogens) or any other active intervention. Two review authors will independently assess the trial eligibility, risk of bias and extract appropriate data points. Trial authors will be contacted for additional data. The primary review outcome is the regression of endometrial hyperplasia histology towards normal histology. Secondary outcomes include hysterectomy rate; abnormal uterine bleeding; quality of life scores and adverse reactions to treatments. Ethics and dissemination

  12. Assessment of endometrial and subendometrial blood flow in women undergoing frozen embryo transfer cycles.

    PubMed

    Nandi, Anupa; Martins, Wellington P; Jayaprakasan, Kannamannadiar; Clewes, Jeanette S; Campbell, Bruce K; Raine-Fenning, Nicholas J

    2014-03-01

    This study evaluated whether 3D power Doppler (3DPD) indices from endometrium and subendometrium can identify increases in endometrial volume/vascularity induced by exogenous oestradiol and subsequent introduction of progestogens in women undergoing frozen-thawed embryo transfer (FET). Oral oestradiol was administered at increasing doses after down-regulation to prepare the endometrium and progestogens were used for luteal support. 3DPD data sets were acquired at down-regulation, on days 5, 10 and 15 of oestradiol administration and at the time of FET. Endometrial thickness was measured using the multiplanar method and endometrial volume and blood flow from the endometrium and subendometrium were estimated using virtual organ computer-aided analysis and shell-imaging. This study evaluated 45 women at least once: 19 achieved clinical pregnancy (CP); 21 were evaluated at down-regulation (eight CP), 26 at day 5 (10 CP), 31 at day 10 (12 CP), 31 at day 15 (13 CP) and 16 at FET (seven CP). Changes were observed in all parameters between the examinations; however, differences between women who achieved CP and those who did not were not significant. 3DPD angiography is not a sufficiently sensitive tool to predict the outcome of FET. We evaluate whether 3D ultrasound using power Doppler (3DPD) indices from endometrium and subendometrium can identify predictable increases in endometrial volume and vascularity induced by serial increments in exogenous oestradiol and the subsequent introduction of progestogens in women undergoing frozen-thawed embryo transfer (FET) using hormone replacement therapy to prepare the endometrium. Oral oestradiol was administered at increasing doses after down-regulation to prepare the endometrium and progestogens were used for luteal support. 3DPD data sets of the uterus were acquired at down-regulation, on days 5, 10, and 15 of oestradiol administration, and at the time of FET. Endometrial thickness was measured. Endometrial volume and blood

  13. Uterine development and endometrial programming.

    PubMed

    Bartol, F F; Wiley, A A; Bagnell, C A

    2006-01-01

    Structural patterning and functional programming of uterine tissues are mechanistically coupled. These processes ensure anteroposterior differentiation of uterine tissues from adjacent segments of the developing female reproductive tract (FRT) and radial patterning that establishes uterine-specific histoarchitecture and functionality. Uterine organogenesis begins prenatally and is completed postnatally. Genes required for FRT development include Pax2, Lim1 and Emx2, genes in the abdominal-B Hoxa cluster, and members of both Wnt and Hedgehog (Hh) gene families. Disruption of morphoregulatory gene expression patterns can prevent FRT development entirely or compromise uterine organogenesis specifically. Oestrogen receptor-alpha (ER) -dependent events associated with development of the neonatal porcine uterus can be altered by administration of oestrogen (E) or relaxin (RLX). Expression of the RLX receptor is detectable in porcine endometrium at birth, before onset of ER expression and uterine gland genesis. Uterotrophic effects of both E and RLX can be inhibited with the ER antagonist ICl 182,780, indicating that RLX may act via crosstalk with the ER system in neonatal tissues. Exposure of neonatal gilts to E alters temporospatial patterns of Hh, Wnt and Hoxa expression in the uterine wall. Oestrogen given for two weeks from birth produced hypoplastic adult porcine uteri that were less responsive to periattachment conceptus signals as reflected by reduced growth response and luminal fluid protein accumulation, altered endometrial gene expression, and reduced capacity for conceptus support. Data reinforce the concept that factors affecting signalling events in uterine tissues that produce changes in morphoregulatory gene expression patterns during critical organisational periods can alter the developmental trajectory of the uterus with lasting consequences. Thus, uterine tissues can be programmed epigenetically for success or failure during perinatal life. PMID

  14. Endometrial Expression of Steroidogenic Factor 1 Promotes Cystic Glandular Morphogenesis.

    PubMed

    Vasquez, Yasmin M; Wu, San-Pin; Anderson, Matthew L; Hawkins, Shannon M; Creighton, Chad J; Ray, Madhumita; Tsai, Sophia Y; Tsai, Ming-Jer; Lydon, John P; DeMayo, Francesco J

    2016-05-01

    Epigenetic silencing of steroidogenic factor 1 (SF1) is lost in endometriosis, potentially contributing to de novo local steroidogenesis favoring inflammation and growth of ectopic endometrial tissue. In this study, we examine the impact of SF1 expression in the eutopic uterus by a novel mouse model that conditionally expresses SF1 in endometrium. In vivo SF1 expression promoted the development of enlarged endometrial glands and attenuated estrogen and progesterone responsiveness. Endometriosis induction by autotransplantation of uterine tissue to the mesenteric membrane resulted in the increase in size of ectopic lesions from SF1-expressing mice. By integrating the SF1-dependent transcriptome with the whole genome binding profile of SF1, we identified uterine-specific SF1-regulated genes involved in Wingless and Progesterone receptor-Hedgehog-Chicken ovalbumin upstream promoter transcription factor II signaling for gland development and epithelium-stroma interaction, respectively. The present results indicate that SF1 directly contributes to the abnormal uterine gland morphogenesis, an inhibition of steroid hormone signaling and activation of an immune response, in addition to previously postulated estrogen production. PMID:27018534

  15. Endometrial evaluation with transvaginal ultrasonography for the screening of endometrial hyperplasia or cancer in premenopausal and perimenopausal women

    PubMed Central

    Kim, Min-Jeong; Kim, Jin-Ju

    2016-01-01

    Objective The aim of our study is to determine clinical factors and sonographic findings associated with endometrial hyperplasia or cancer (EH+) in premenopausal and perimenopausal women. Methods A total of 14,340 transvaginal ultrasonography examinations of 9,888 healthy premenopausal and perimenopausal women were included in this retrospective study. One hundred sixty-two subjects underwent endometrial biopsy based on abnormal uterine bleeding (AUB), sonographic endometrial abnormalities (thickened endometrium, endometrial mass, or endometrial stripe abnormality), or both. The clinical factors and sonographic endometrial abnormalities were evaluated with regard to EH+. Results Histologically verified EH+ was found in fourteen subjects (8.6%); ten cases of endometrial hyperplasia (EH) without atypia, three cases of EH with atypia (AEH), and one case of endometrial cancer. Neither clinical factors nor AUB were associated with EH+ (P=0.32) or AEH+ (P=0.72). Of sonographic findings, endometrial stripe abnormality was significantly associated with EH+ (P=0.003) and marginally associated with AEH+ (P=0.05), but a thickened endometrium was not associated with EH+ (P=0.43). Conclusion Endometrial stripe abnormality is a significant factor to predict EH+ in healthy premenopausal and perimenopausal women with and without AUB. However, simple measurement of endometrial thickness has a limited role in this capacity. PMID:27200309

  16. p53 suppresses type II endometrial carcinomas in mice and governs endometrial tumour aggressiveness in humans

    PubMed Central

    Wild, Peter J; Ikenberg, Kristian; Fuchs, Thomas J; Rechsteiner, Markus; Georgiev, Strahil; Fankhauser, Niklaus; Noske, Aurelia; Roessle, Matthias; Caduff, Rosmarie; Dellas, Athanassios; Fink, Daniel; Moch, Holger; Krek, Wilhelm; Frew, Ian J

    2012-01-01

    Type II endometrial carcinomas are a highly aggressive group of tumour subtypes that are frequently associated with inactivation of the TP53 tumour suppressor gene. We show that mice with endometrium-specific deletion of Trp53 initially exhibited histological changes that are identical to known precursor lesions of type II endometrial carcinomas in humans and later developed carcinomas representing all type II subtypes. The mTORC1 signalling pathway was frequently activated in these precursor lesions and tumours, suggesting a genetic cooperation between this pathway and Trp53 deficiency in tumour initiation. Consistent with this idea, analyses of 521 human endometrial carcinomas identified frequent mTORC1 pathway activation in type I as well as type II endometrial carcinoma subtypes. mTORC1 pathway activation and p53 expression or mutation status each independently predicted poor patient survival. We suggest that molecular alterations in p53 and the mTORC1 pathway play different roles in the initiation of the different endometrial cancer subtypes, but that combined p53 inactivation and mTORC1 pathway activation are unifying pathogenic features among histologically diverse subtypes of late stage aggressive endometrial tumours. PMID:22678923

  17. ZEB1 Expression in Endometrial Biopsy Predicts Lymph Node Metastases in Patient with Endometrial Cancer

    PubMed Central

    Feng, Gang; Wang, Xiangming; Cao, Xiaozhi; Shen, Lijuan; Zhu, Jiansheng

    2014-01-01

    Purpose. The purpose of this study was to analyze the expression of zinc-finger E-box-binding homeobox 1 (ZEB1) in endometrial biopsy and its correlation with preoperative characteristics, including lymph node metastases in patient with endometrial cancer. Methods. Using quantitative RT-PCR, ZEB1 expressions in endometrial biopsy from 452 patients were measured. The relationship between ZEB1 expression and preoperative characteristics was analyzed. Results. ZEB1 expressions were significantly associated with subtype, grade, myometrial invasion, and lymph node metastases. Lymph node metastases could be identified with a sensitivity of 57.8% at specificity of 74.1% by ZEB1 expression in endometrial biopsy. Based on combination of preoperative characteristics and ZEB1 expression, lymph node metastases could be identified with a sensitivity of 62.1% at specificity of 96.2% prior to hysterectomy. Conclusion. ZEB1 expression in endometrial biopsy could help physicians to better predict the lymph node metastasis in patients with endometrial cancer prior to hysterectomy. PMID:25544793

  18. Five endometrial cancer risk loci identified through genome-wide association analysis.

    PubMed

    Cheng, Timothy H T; Thompson, Deborah J; O'Mara, Tracy A; Painter, Jodie N; Glubb, Dylan M; Flach, Susanne; Lewis, Annabelle; French, Juliet D; Freeman-Mills, Luke; Church, David; Gorman, Maggie; Martin, Lynn; Hodgson, Shirley; Webb, Penelope M; Attia, John; Holliday, Elizabeth G; McEvoy, Mark; Scott, Rodney J; Henders, Anjali K; Martin, Nicholas G; Montgomery, Grant W; Nyholt, Dale R; Ahmed, Shahana; Healey, Catherine S; Shah, Mitul; Dennis, Joe; Fasching, Peter A; Beckmann, Matthias W; Hein, Alexander; Ekici, Arif B; Hall, Per; Czene, Kamila; Darabi, Hatef; Li, Jingmei; Dörk, Thilo; Dürst, Matthias; Hillemanns, Peter; Runnebaum, Ingo; Amant, Frederic; Schrauwen, Stefanie; Zhao, Hui; Lambrechts, Diether; Depreeuw, Jeroen; Dowdy, Sean C; Goode, Ellen L; Fridley, Brooke L; Winham, Stacey J; Njølstad, Tormund S; Salvesen, Helga B; Trovik, Jone; Werner, Henrica M J; Ashton, Katie; Otton, Geoffrey; Proietto, Tony; Liu, Tao; Mints, Miriam; Tham, Emma; Li, Mulin Jun; Yip, Shun H; Wang, Junwen; Bolla, Manjeet K; Michailidou, Kyriaki; Wang, Qin; Tyrer, Jonathan P; Dunlop, Malcolm; Houlston, Richard; Palles, Claire; Hopper, John L; Peto, Julian; Swerdlow, Anthony J; Burwinkel, Barbara; Brenner, Hermann; Meindl, Alfons; Brauch, Hiltrud; Lindblom, Annika; Chang-Claude, Jenny; Couch, Fergus J; Giles, Graham G; Kristensen, Vessela N; Cox, Angela; Cunningham, Julie M; Pharoah, Paul D P; Dunning, Alison M; Edwards, Stacey L; Easton, Douglas F; Tomlinson, Ian; Spurdle, Amanda B

    2016-06-01

    We conducted a meta-analysis of three endometrial cancer genome-wide association studies (GWAS) and two follow-up phases totaling 7,737 endometrial cancer cases and 37,144 controls of European ancestry. Genome-wide imputation and meta-analysis identified five new risk loci of genome-wide significance at likely regulatory regions on chromosomes 13q22.1 (rs11841589, near KLF5), 6q22.31 (rs13328298, in LOC643623 and near HEY2 and NCOA7), 8q24.21 (rs4733613, telomeric to MYC), 15q15.1 (rs937213, in EIF2AK4, near BMF) and 14q32.33 (rs2498796, in AKT1, near SIVA1). We also found a second independent 8q24.21 signal (rs17232730). Functional studies of the 13q22.1 locus showed that rs9600103 (pairwise r(2) = 0.98 with rs11841589) is located in a region of active chromatin that interacts with the KLF5 promoter region. The rs9600103[T] allele that is protective in endometrial cancer suppressed gene expression in vitro, suggesting that regulation of the expression of KLF5, a gene linked to uterine development, is implicated in tumorigenesis. These findings provide enhanced insight into the genetic and biological basis of endometrial cancer. PMID:27135401

  19. Endometrial thickness and risk of breast and endometrial carcinomas in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

    PubMed Central

    Felix, Ashley S.; Weissfeld, Joel L.; Pfeiffer, Ruth M.; Modugno, Francesmary; Black, Amanda; Hill, Lyndon M.; Martin, Jerry; Sit, Anita S.; Sherman, Mark E.; Brinton, Louise A.

    2013-01-01

    Postmenopausal women with higher circulating estrogen levels are at increased risk of developing breast and endometrial carcinomas. In the endometrium, excess estrogen relative to progesterone produces a net proliferative stimulus, which may result in endometrial thickening. Therefore, we tested the hypothesis that endometrial thickness is a biological marker of excess estrogen stimulation that is associated with risk of breast and endometrial carcinomas. Endometrial thickness was measured in 1,272 postmenopausal women, aged 55–74, who underwent transvaginal ultrasound (TVU) screening as part of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Serial endometrial thickness measurements were available for a subset of women at one (n=1,018), two (n=869) and three years (n=641) after baseline. We evaluated associations between endometrial thickness and breast (n=91) and endometrial (n=14) carcinoma by estimating relative risks (RRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression with age as the time metric. Models incorporating baseline endometrial thickness and as a time-varying covariate using all measurements were examined. Median follow-up among study participants was 12.5 years (range: 0.3–13.8 years). Compared to baseline endometrial thickness of 1.0 – 2.99 mm, women with baseline endometrial thickness greater than or equal to 5.0 mm had an increased risk of breast (RR: 2.00, 95% CI 1.15, 3.48) and endometrial (RR: 5.02, 95% CI 0.96, 26.36) carcinomas in models adjusted for menopausal hormone use and BMI. Our data suggest that increased endometrial thickness as assessed by TVU was associated with increased risk of breast and endometrial carcinomas. PMID:23907658

  20. 21 CFR 884.1060 - Endometrial aspirator.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Endometrial aspirator. 884.1060 Section 884.1060... endometrium, and (ii) Contraindications: Pregnancy, history of uterine perforation, or a recent cesarean section, and (3) The sampling component is covered within vagina....

  1. 21 CFR 884.1060 - Endometrial aspirator.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Endometrial aspirator. 884.1060 Section 884.1060... endometrium, and (ii) Contraindications: Pregnancy, history of uterine perforation, or a recent cesarean section, and (3) The sampling component is covered within vagina....

  2. 21 CFR 884.1185 - Endometrial washer.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... a recent cesarean section, and (iii) Warning: Do not attach to a wall or any external suction, and... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Endometrial washer. 884.1185 Section 884.1185 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED)...

  3. 21 CFR 884.1100 - Endometrial brush.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... perforation, or a recent cesarean section, and (3) Design and testing: (i) The sampling component is covered... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Endometrial brush. 884.1100 Section 884.1100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED)...

  4. 21 CFR 884.1185 - Endometrial washer.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... a recent cesarean section, and (iii) Warning: Do not attach to a wall or any external suction, and... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Endometrial washer. 884.1185 Section 884.1185 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED)...

  5. 21 CFR 884.1060 - Endometrial aspirator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Endometrial aspirator. 884.1060 Section 884.1060... endometrium, and (ii) Contraindications: Pregnancy, history of uterine perforation, or a recent cesarean section, and (3) The sampling component is covered within vagina....

  6. 21 CFR 884.1185 - Endometrial washer.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... a recent cesarean section, and (iii) Warning: Do not attach to a wall or any external suction, and... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Endometrial washer. 884.1185 Section 884.1185 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED)...

  7. 21 CFR 884.1100 - Endometrial brush.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... perforation, or a recent cesarean section, and (3) Design and testing: (i) The sampling component is covered... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Endometrial brush. 884.1100 Section 884.1100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED)...

  8. 21 CFR 884.1100 - Endometrial brush.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... perforation, or a recent cesarean section, and (3) Design and testing: (i) The sampling component is covered... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Endometrial brush. 884.1100 Section 884.1100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED)...

  9. Postmenopausal tamoxifen treatment and endometrial pathology.

    PubMed

    Cohen, I; Altaras, M M; Shapira, J; Tepper, R; Beyth, Y

    1994-12-01

    Tamoxifen is widely used as adjuvant therapy for postmenopausal breast cancer patients with positive estrogen receptors. Data on a possible association of endometrial pathologies with tamoxifen treatment have been accumulating. In this review, we examine the current literature and include our own experience with this occurrence. We recommend close supervision of these patients. PMID:7885659

  10. Endometrial study in patients with postmenopausal metrorrhagia

    PubMed Central

    de Merlo, Gaspar González; Mirasol, Esteban González; García, María Teresa Gómez; Parra, Carmen Ángel; Goy, Enrique Iglesias

    2016-01-01

    Introduction The aim of the study was to devise a strategy to diagnose malign endometrial pathologies (adenocarcinoma or atypical hyperplasia) that minimizes the number of invasive tests done (hysteroscopy, aspiration biopsy or curettage) with no loss of its detection efficiency. Material and methods We retrospectively studied the clinical histories of 779 postmenopausal women at the University Hospital Complex of Albacete, for whom an endometrial study had been done (hysteroscopy, aspiration biopsy or curettage) with a 1-year follow-up between 1 March 2006 and 31 March 2008. Results There were 77 cases of a malignant pathology (66 adenocarcinomas and 11 hyperplasias with atypia); 96.1% had metrorrhagia, and there were only 3 cases of asymptomatic patients (all 3 presented endometrial thickness of > 5 mm: 10, 12 and 15 mm). The sensitivity and specificity of the transvaginal ultrasound, with a 5 mm cut-off point to diagnose a malignant pathology, were 98.4% and 30.1%, respectively; 89.1% and 99.6%, respectively, for aspiration biopsy; 83.9% and 99.1%, respectively, for hysteroscopy without biopsy; and both were 100% for biopsy. Statistical significance was considered at p < 0.05 and confidence intervals were calculated at 95%. Conclusions In postmenopausal women with metrorrhagia, the first action to take is to do a transvaginal ultrasound, followed by en endometrial study, but only if the endometrium is irregular or endometrial thickness is ≥ 5 mm; in asymptomatic women, the cut-off point should be set at 10 mm. The immediate method of choice is an ambulatory biopsy. PMID:27279854