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Sample records for dialogue regulating endometrial

  1. 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.

  2. Lower Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Promotes the Proliferation and Migration of Endometrial Carcinoma

    PubMed Central

    Xia, Xian; Wang, Jie; Liu, Yuan; Yue, Ming

    2017-01-01

    Background The incidence and death rates of endometrial cancer are alarmingly increasing. The diagnosis and treatment of endometrial cancer is crucial to decreasing mortality. Cystic fibrosis transmembrane conductance regulator (CFTR) belongs to the adenosine triphosphate (ATP)-binding cassette transporter family and plays an essential role in anion regulation and tissue homeostasis of various epithelia. This study explored the expression of CFTR in endometrial carcinoma and the role of CFTR in proliferation and migration of endometrial carcinoma cells. Material/Methods Immunohistochemistry and real-time (RT)-PCR were used to test the expression of CFTR in normal endometrium and endometrial carcinoma. CFTR inhibitor was used to restrain the expression of CFTR on the endometrial carcinoma, the effects on the proliferation and migration of endometrial carcinoma cells were also studied. RT-PCR was performed to test the expression of mir-125b after restraining CFTR. Proliferation and migration capability of endometrial carcinoma cells were detected after transfection of endometrial carcinoma cells with mir-125b mimic. Results Compared with cells from normal endometrium, the expression of CFTR was significantly upregulated in endometrial carcinoma cells. After adding CFTR(inh)172, the capability for proliferation and transfer of endometrial carcinoma cells was strengthened, the expression of mir-125b was reduced, and after transfection with mir-125b mimics entering the endometrial carcinoma cells, the ability of the proliferation and transfer of endometrial carcinoma cells was also reduced. Conclusions The high expression of CFTR in the endometrial carcinoma cells played a pivotal role in restraining the proliferation and transfer of endometrial carcinoma cells. PMID:28225751

  3. Lower Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Promotes the Proliferation and Migration of Endometrial Carcinoma.

    PubMed

    Xia, Xian; Wang, Jie; Liu, Yuan; Yue, Ming

    2017-02-22

    BACKGROUND The incidence and death rates of endometrial cancer are alarmingly increasing. The diagnosis and treatment of endometrial cancer is crucial to decreasing mortality. Cystic fibrosis transmembrane conductance regulator (CFTR) belongs to the adenosine triphosphate (ATP)-binding cassette transporter family and plays an essential role in anion regulation and tissue homeostasis of various epithelia. This study explored the expression of CFTR in endometrial carcinoma and the role of CFTR in proliferation and migration of endometrial carcinoma cells. MATERIAL AND METHODS Immunohistochemistry and real-time (RT)-PCR were used to test the expression of CFTR in normal endometrium and endometrial carcinoma. CFTR inhibitor was used to restrain the expression of CFTR on the endometrial carcinoma, the effects on the proliferation and migration of endometrial carcinoma cells were also studied. RT-PCR was performed to test the expression of mir-125b after restraining CFTR. Proliferation and migration capability of endometrial carcinoma cells were detected after transfection of endometrial carcinoma cells with mir-125b mimic. RESULTS Compared with cells from normal endometrium, the expression of CFTR was significantly upregulated in endometrial carcinoma cells. After adding CFTR(inh)172, the capability for proliferation and transfer of endometrial carcinoma cells was strengthened, the expression of mir-125b was reduced, and after transfection with mir-125b mimics entering the endometrial carcinoma cells, the ability of the proliferation and transfer of endometrial carcinoma cells was also reduced. CONCLUSIONS The high expression of CFTR in the endometrial carcinoma cells played a pivotal role in restraining the proliferation and transfer of endometrial carcinoma cells.

  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. 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.

  7. Endometrial Cancer and Hypermethylation: Regulation of DNA and MicroRNA by Epigenetics

    PubMed Central

    Banno, Kouji; Kisu, Iori; Yanokura, Megumi; Masuda, Kenta; Kobayashi, Yusuke; Ueki, Arisa; Tsuji, Kosuke; Yamagami, Wataru; Nomura, Hiroyuki; Susumu, Nobuyuki; Aoki, Daisuke

    2012-01-01

    Endometrial cancer is the seventh most common cancer in women worldwide. Therefore elucidation of the pathogenesis and development of effective treatment for endometrial cancer are important. However, several aspects of the mechanism of carcinogenesis in the endometrium remain unclear. Associations with genetic variation and mutations of cancer-related genes have been shown, but these do not provide a complete explanation. Therefore, in recent years, epigenetic mechanisms that do not involve changes in DNA sequences have been examined. Studies aimed at detection of aberrant DNA hypermethylation in cancer cells present in microscopic amounts in vivo and application of the results to cancer diagnosis have also started. Breakdown of the DNA mismatch repair mechanism is thought to play a large role in the development of endometrial cancer, with changes in the expression of the hMLH1 gene being particularly important. Silencing of genes such as APC and CHFR, Sprouty 2, RASSF1A, GPR54, CDH1, and RSK4 by DNA hypermethylation, onset of Lynch syndrome due to hereditary epimutation of hMLH1 and hMSH2 mismatch repair genes, and regulation of gene expression by microRNAs may also underlie the carcinogenic mechanisms of endometrial cancer. Further understanding of these issues may permit development of new therapies. PMID:22548175

  8. Leptin regulation of the interleukin-1 system in human endometrial cells.

    PubMed

    Gonzalez, Ruben Rene; Leary, Kristen; Petrozza, John Christopher; Leavis, Paul Clifton

    2003-03-01

    We have previously shown that (i). leptin and leptin receptor (Ob-R) are expressed in the human endometrium, and (ii). leptin secretion is regulated in blastocyst and endometrial epithelial cell (EEC) co-cultures. Interleukin-1beta (IL-1beta) up-regulates leptin and Ob-R, and both cytokines up-regulate beta3 integrin expression in EEC. In the present investigation we examined the effect of leptin on the expression of the IL-1 system in EEC and endometrial stromal cells (ESC) cultured in a medium containing insulin, leptin or IL-1beta (0-3 nmol/l). Leptin stimulated IL-1 antagonist (IL-1Ra), IL-1beta secretion and expression of IL-1 receptor type I (IL-1R tI) in both cell types. IL-1beta and IL-1Ra secretion were down-regulated by IL-1R tI blockade using specific antibodies. Interestingly, leptin partially neutralized this effect. The blockade of Ob-R neutralized the effects of both leptin and IL-1beta on expression of the IL-1beta system and beta3 integrin and on phosphorylation of signal transducer and activator of transcription 3 (Stat3). These results suggest that leptin regulates the IL-1 system and that the blockade of functional Ob-R impairs leptin and IL-1beta functions at the endometrial level. Leptin could be an important molecule for implantation and a molecular mediator for actions of the IL-1 system. The fact that leptin, in the absence of IL-1, can trigger the expression of markers of endometrial receptivity and of the invasive trophoblast phenotype (as does IL-1), suggest that leptin could substitute for these IL-1 functions during the implantation process.

  9. Human Endometrial Adenocarcinoma Transplanted into Nude Mice: Growth Regulation by Estradiol

    NASA Astrophysics Data System (ADS)

    Satyaswaroop, P. G.; Zaino, R. J.; Mortel, R.

    1983-01-01

    A model for studying the growth of primary tumors of human endometrium and its regulation by 17β -estradiol has been developed in which ovariectomized nude mice are used as recipients. The receptors for sex steroids are maintained during serial transplantation of the tumor in this system. Although the rate of growth of receptor-negative endometrial tumors transplanted into ovariectomized nude mice is unaffected by the sustained presence or absence of estradiol, the growth of receptor-positive tumors is significantly increased by estradiol. Receptor-positive tumors treated with estradiol produced elevated concentrations of progesterone receptor. That the progesterone receptor is functional in this tumor is evident from the induction of estradiol 17β -dehydrogenase activity upon progestin administration. These findings are consistent with receptor-mediated regulation of growth of endometrial carcinoma.

  10. DNMT1 regulates human endometrial carcinoma cell proliferation

    PubMed Central

    Wang, Xinjing; Li, Bilan

    2017-01-01

    Endometrial carcinoma (EC) is the most common gynecologic malignancy, but the molecular events involved in the development and progression of EC remain unclear. This study aimed to investigate the role of DNA methyltransferase 1 (DNMT1), a member of DNA methyltransferases, in EC. AN3CA cells were transfected with DNMT1 siRNA. The proliferation, cell cycle, and apoptosis of AN3CA cells were evaluated by Cell Counting Kit-8 (CCK-8) assay and flow cytometry. The expression of related genes was detected by polymerase chain reaction and Western blot analysis. Knockdown of DNMT1 inhibited the proliferation, induced apoptosis, and G0/G1 phase arrest of AN3CA cells. Furthermore, knockdown of DNMT1 upregulated the expression of nuclear factor kappa-B-inhibitor alpha (NF-κBIA) and Bax and downregulated the expression of Bcl-2 and CCND1/2 in AN3CA cells. In conclusion, this study provides the first evidence that knockdown of DNMT1 affects the expression of cell cycle- and apoptosis-associated proteins in EC cells, suggesting the potential of DNMT1 in EC therapy.

  11. Endometrial ablation

    MedlinePlus

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

  12. Self-Regulation and Metacognition in Young Children's Self-Initiated Play and Reflective Dialogue

    ERIC Educational Resources Information Center

    Robson, Sue

    2010-01-01

    This paper looks at ways in which a group of children aged three-four years exhibited evidence of self-regulation and metacognition. Videotaped episodes of children's activities and audiotaped dialogues between children and practitioners about the activities were analysed using an observational framework. The data here show children of three and…

  13. Dynamic remodeling of endometrial extracellular matrix regulates embryo receptivity in cattle.

    PubMed

    Scolari, Saara Carollina; Pugliesi, Guilherme; Strefezzi, Ricardo de Francisco; Andrade, Sónia Cristina; Coutinho, Luiz Lehmann; Binelli, Mario

    2016-10-17

    We aimed to evaluate in the bovine endometrium whether (1) key genes involved in endometrial extracellular matrix (ECM) remodeling are regulated by the endocrine peri-ovulatory milieu; and (2) specific endometrial ECM-related transcriptome can be linked to pregnancy outcome. In Experiment 1, pre-ovulatory follicle growth of cows was manipulated to obtain two groups with specific endocrine peri-ovulatory profiles: the Large Follicle-Large CL group (LF-LCL) served as a paradigm for greater receptivity and fertility and showed greater plasma pre-ovulatory estradiol and post-ovulatory progesterone concentrations when compared to the Small Follicle-Small CL group (SF-SCL). Endometrium was collected on days 4 and 7 of the estrous cycle. Histology revealed a greater abundance of total collagen content in SF-SCL on day 4 endometrium. In Experiment 2, cows were artificially inseminated and, six days later, endometrial biopsies were collected. Cows were retrospectively divided into pregnant and non-pregnant (P vs. NP) groups after diagnosis on day 30. In both experiments, expression of genes related to ECM remodeling in the endometrium was studied by RNAseq and qPCR. Gene ontology analysis showed an inhibition in the expression of ECM-related genes in the high receptivity groups (LF-LCL and P). Specifically, there was down-regulation of TGFB2, ADAMTS2, 5 and 14, TIMP3 and COL1A2, COL3A1, COL7A1 and COL3A3 in the LF-LCL and P groups. In summary, the overlapping set of genes differently expressed in both fertility models: (1) suggests that disregulation of ECM remodeling can impair receptivity and (2) can be used as markers to predict pregnancy outcome in cattle.

  14. 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.

  15. 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-...

  16. 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.

  17. 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.

  18. Regulation of chloride secretion across porcine endometrial epithelial cells by prostaglandin E2.

    PubMed

    Deachapunya, C; O'Grady, S M

    1998-04-01

    1. The objective of this study was to investigate the mechanism of PGE2 regulation of Cl- transport across glandular endometrial cells grown in primary culture. 2. Most of the basal short circuit current (Isc) was inhibited by luminal addition of 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB) or glibenclamide, suggesting the presence of a basally active Cl- conductance in the apical membrane. 3. Basolateral addition of 10 microM PGE2 increased Isc by 41 +/- 3 microA. A similar response was observed when cells were treated with 8-(4-chlorophenylthio) adenosine 3',5'-cyclic monophosphate (CPT-cAMP). Pretreatment of monolayers with NPPB and glibenclamide blocked the PGE2 and cAMP-mediated increase in Isc, suggesting that the effects of PGE2 and cAMP were dependent on the activity of an apical NPPB- and glibenclamide-sensitive conductance. 4. Addition of 50 nM antiPGE2 antibody to the basolateral bathing solution decreased basal Isc by 20 % and shifted the threshold response to exogenous PGE2. This result suggests autocrine regulation of electrogenic Cl- transport by PGE2. 5. Experiments with amphotericin B-permeabilized monolayers revealed that the apical PGE2-activated, NPPB- and glibenclamide-sensitive conductance was Cl- dependent and that the current-voltage relationship and anion permeation properties (SCN->Br- > Cl- > I-) were characteristic of the cystic fibrosis transmembrane conductance regulator (CFTR). 6. Cultured porcine endometrial epithelial cells were specifically labelled with an antibody to a peptide sequence within the regulatory domain of CFTR. 7. The effect of PGE2 was blocked by basolateral addition of bumetanide and furosemide at concentrations that are selective for inhibition of Na+-K+-2Cl-cotransport activity. The effect of bumetanide on Isc was Cl- dependent, suggesting a role for the bumetanide-sensitive transport pathway in Cl- secretion. 8. PGE2 and cAMP also activated an outwardly rectifying basolateral K+ channel which presumably

  19. Seminal plasma regulates endometrial cytokine expression, leukocyte recruitment and embryo development in the pig.

    PubMed

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

    2004-08-01

    In pigs, uterine exposure to the constituents of semen is known to increase litter size but the underlying physiological mechanisms remain undefined. Studies in rodents and humans implicate immune modulating moieties in seminal plasma as likely candidates, acting through enhancing the receptivity of the female tract. In this study, the acute and longer term effects of seminal plasma on cytokine expression and leukocyte abundance in the pig endometrium during early pregnancy have been characterised. The reproductive tracts of gonadotrophin-primed pre-pubertal gilts treated with intrauterine infusions of either pooled seminal plasma or phosphate-buffered saline (PBS) were retrieved at 34 h, or on day 5 and day 9 after treatment. Seminal plasma elicited an endometrial inflammatory infiltrate comprised of predominantly macrophages and major histocompatibility complex class II+-activated macrophages and dendritic cells. The abundance of these cells was greatest at the pre-ovulatory (34 h) time-point and their increase relative to PBS-treated tissues was maintained until day 9 after seminal plasma treatment. Seminal plasma induced the expression of the cytokines, granulocyte macrophage colony-stimulating factor, interleukin-6 and monocyte chemoattractant protein-1, and the eicosanoid-synthesising enzyme cyclo-oxygenase-2. Expression was maximal 34 h after treatment but altered expression patterns as a consequence of seminal plasma induction persisted through early pregnancy. These changes were accompanied by altered dynamics in pre-implantation embryo development with an increase in the number of embryos and in their viability after seminal plasma treatment. Together, these findings implicate factors in seminal plasma in programming the trajectory of uterine cytokine expression and leukocyte trafficking during early pregnancy and in regulating pre-implantation embryo development in the pig.

  20. Ovarian steroids, mitogen-activated protein kinases, and/or aspartic proteinases cooperate to control endometrial remodeling by regulating gene expression in the stroma and glands.

    PubMed

    Gaide Chevronnay, Héloïse P; Lemoine, Pascale; Courtoy, Pierre J; Marbaix, Etienne; Henriet, Patrick

    2010-09-01

    Explants from nonmenstrual endometria cultured in the absence of ovarian hormones undergo tissue breakdown. Addition of estradiol and progesterone (EP) prevents proteolysis. Explants include stromal and epithelial compartments which play different but complementary roles in endometrial physiology, including tissue remodeling and hormonal response. In order to characterize the cell type-specific contribution to regulation of tissue breakdown, we characterized the transcriptomes of microdissected stromal and glandular areas from endometrial explants cultured with or without EP. The datasets were also compared to other published endometrial transcriptomes. Finally, the contribution of proteolysis, hypoxia, and MAPKs to the regulation of selected genes was further investigated in explant culture. This analysis identified distinct gene expression profiles in stroma and glands, with differential response to EP, but functional clustering underlined convergence in biological processes, further indicating that endometrial remodeling requires cooperation between the two compartments through expression of cell type-specific genes. Only partial overlaps were observed between lists of genes involved in different occurrences of endometrial breakdown, pointing to a limited number of potentially crucial regulators but also to the requirement for additional mechanisms controlling tissue remodeling. We identified a group of genes differentially regulated by EP in stroma and glands among which some were sensitive to MAPKs and/or aspartic proteinases and were not induced by hypoxia. In conclusion, MAPKs and/or aspartic proteinases likely act in concert with EP to locally and specifically control differential expression of genes between degrading and preserved areas of the human endometrium.

  1. Nucleophosmin/B23 is a negative regulator of estrogen receptor α expression via AP2γ in endometrial cancer cells

    PubMed Central

    Lee, Li-Yu; Yang, Lan-Yan; Tsai, Chia-Lung; Wang, Hsin-Shih; Lai, Chyong-Huey

    2016-01-01

    Endometrial cancers expressing estrogen and progesterone receptors respond to hormonal therapy. The disappearance of steroid hormone receptor expression is common in patients with recurrent disease, ultimately hampering the clinical utility of hormonal therapy. Here, we demonstrate for the first time that nucleophosmin (NPM1/B23) suppression can restore the expression of estrogen receptor α (ESR1/ERα) in endometrial cancer cells. Mechanistically, B23 and activator protein-2γ (TFAP2C/AP2γ) form a complex that acts as a transcriptional repressor of ERα. Our results indicate that B23 or AP2γ knockdown can restore ERα levels and activate ERα-regulated genes (e.g., cathepsin D, EBAG9, and TFF1/pS2). Moreover, AP2γ knockdown in a xenograft model sensitizes endometrial cancer cells to megesterol acetate through the upregulation of ERα expression. An increased immunohistochemical expression of AP2γ is an adverse prognostic factor in endometrial cancer. In summary, B23 and AP2γ may act in combination to suppress ERα expression in endometrial cancer cells. The inhibition of B23 or AP2γ can restore ERα expression and can serve as a potential strategy for sensitizing hormone-refractory endometrial cancers to endocrine therapy. PMID:27527851

  2. 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...

  3. STAR and AKR1B10 are down-regulated in high-grade endometrial cancer.

    PubMed

    Sinreih, Maša; Štupar, Saša; Čemažar, Luka; Verdenik, Ivan; Frković Grazio, Snježana; Smrkolj, Špela; Rižner, Tea Lanišnik

    2017-02-21

    Endometrial cancer is the most frequent gynecological malignancy in the developed world. The majority of cases are estrogen dependent, and are associated with diminished protective effects of progesterone. Endometrial cancer is also related to enhanced inflammation and decreased differentiation. In our previous studies, we examined the expression of genes involved in estrogen and progesterone actions in inflammation and tumor differentiation, in tissue samples from endometrial cancer and adjacent control endometrium. The aims of the current study were to examine correlations between gene expression and several demographic characteristics, and to evaluate changes in gene expression with regard to histopathological and clinical characteristics of 51 patients. We studied correlations and differences in expression of 38 genes involved in five pathophysiological processes: (i) estrogen-stimulated proliferation; (ii) estrogen-dependent carcinogenesis; (iii) diminished biosynthesis of progesterone: (iv) enhanced formation of progesterone metabolites; and (v) increased inflammation and decreased differentiation. Spearman correlation coefficient analysis shows that expression of PAQR7 correlates with age, expression of SRD5A1, AKR1B1 and AKR1B10 correlate with body mass, while expression of SRD5A1 and AKR1B10 correlate with body mass index. When patients with endometrial cancer were stratified based on menopausal status, histological grade, myometrial invasion, lymphovascular invasion, and FIGO stage, Mann-Whitney U tests revealed significantly decreased expression of STAR (4.4-fold; adjusted p=0.009) and AKR1B10 (9-fold; adjusted p=0.003) in high grade versus low grade tumors. Lower levels of STAR might lead to decreased de-novo steroid hormone synthesis and tumor differentiation, and lower levels of AKR1B10 to diminished elimination of toxic electrophilic carbonyl compounds in high-grade endometrial cancer. These data thus reveal the potential of STAR and AKR1B10 as

  4. Expression and regulation of c-Jun N-terminal kinase (JNK) in endometrial cells in vivo and in vitro.

    PubMed

    Kizilay, Gulnur; Cakmak, Hakan; Yen, Chih-Feng; Atabekoglu, Cem; Arici, Aydin; Kayisli, Umit Ali

    2008-10-01

    JNK(c-Jun N-terminal kinase) is one of the main types of mitogen-activated protein kinases. JNK modulates inflammation and apoptosis in response to stress. Our hypothesis is that temporal and spatial changes in JNK activity regulate inflammation in human endometrium and that fluctuation in estrogen and progesterone levels may play a role in JNK activation. Therefore, we aimed to determine total-(t-) and active-(phosphorylated, p-) JNK expression in endometrial tissues in vivo by immunohistochemistry, and in vitro by immunocytochemistry and Western blot analysis. Immunohistochemistry revealed moderate cytoplasmic and nuclear t-JNK immunoreactivity, and mostly nuclear p-JNK immunoreactivity throughout the menstrual cycle and early pregnancy. The highest p- and t-JNK immunoreactivity was detected in late secretory phase (P < 0.05). We observed that endometrial stromal cell (ESC)s showed a significant increase in p-JNK expression following 48 h of estrogen combined with progesterone (E(2) + P(4)) withdrawal from the culture conditions, compared to control and non-withdrawal groups (P < 0.05). Upon treatment with JNK inhibitor SP600125, we observed a significantly decreased interleukin (IL)-8 level (P < 0.05) in the presence and absence of E(2). These results demonstrate that JNK expression increases during the late secretory phase when the inflammatory response is highest. Inhibition of IL-8 expression by SP600125 suggests that JNK is involved in regulation of proinflammatory mediators of endometrium.

  5. Activin B promotes endometrial cancer cell migration by down-regulating E-cadherin via SMAD-independent MEK-ERK1/2-SNAIL signaling

    PubMed Central

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

    2016-01-01

    High-risk type II endometrial cancers account for ~30% of cases but ~75% of deaths due, in part, to their tendency to metastasize. Histopathological studies of type II endometrial cancers (non-endometrioid, mostly serous) suggest overproduction of activin B and down-regulation of E-cadherin, both of which are associated with reduced survival. Our previous studies have shown that activin B increases the migration of type II endometrial cancer cell lines. However, little is known about the relationship between activin B signaling and E-cadherin in endometrial cancer. We now demonstrate that activin B treatment significantly decreases E-cadherin expression in both a time- and concentration-dependent manner in KLE and HEC-50 cell lines. Interestingly, these effects were not inhibited by knockdown of SMAD2, SMAD3 or SMAD4. Rather, the suppressive effects of activin B on E-cadherin were mediated by MEK-ERK1/2-induced production of the transcription factor SNAIL. Importantly, activin B-induced cell migration was inhibited by forced-expression of E-cadherin or pre-treatment with the activin/TGF-β type I receptor inhibitor SB431542 or the MEK inhibitor U0126. We have identified a novel SMAD-independent pathway linking enhanced activin B signaling to reduced E-cadherin expression and increased migration in type II endometrial cancer. PMID:27223076

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

    PubMed

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

    2015-12-01

    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

  7. 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

  8. 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

  9. Human Blastocyst Secreted microRNA Regulate Endometrial Epithelial Cell Adhesion

    PubMed Central

    Cuman, Carly; Van Sinderen, Michelle; Gantier, Michael P.; Rainczuk, Kate; Sorby, Kelli; Rombauts, Luk; Osianlis, Tiki; Dimitriadis, Evdokia

    2015-01-01

    Successful embryo implantation requires synchronous development and communication between the blastocyst and the endometrium, however the mechanisms of communication in humans are virtually unknown. Recent studies have revealed that microRNAs (miRs) are present in bodily fluids and secreted by cells in culture. We have identified that human blastocysts differentially secrete miRs in a pattern associated with their implantation outcome. miR-661 was the most highly expressed miR in blastocyst culture media (BCM) from blastocysts that failed to implant (non-implanted) compared to blastocysts that implanted (implanted). Our results indicate a possible role for Argonaute 1 in the transport of miR-661 in non-implanted BCM and taken up by primary human endometrial epithelial cells (HEECs). miR-661 uptake by HEEC reduced trophoblast cell line spheroid attachment to HEEC via PVRL1. Our results suggest that human blastocysts alter the endometrial epithelial adhesion, the initiating event of implantation, via the secretion of miR, abnormalities in which result in implantation failure. PMID:26629549

  10. 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 ...

  11. Endometrial polyps

    MedlinePlus

    ... cancer is higher if you are postmenopausal, on Tamoxifen, or have heavy or irregular periods. These factors may increase the risk for endometrial polyps: Obesity Tamoxifen, a treatment for breast cancer Postmenopausal hormone replacement ...

  12. 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? ...

  13. 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 • ...

  14. Protocadherin 10 inhibits cell proliferation and induces apoptosis via regulation of DEP domain containing 1 in endometrial endometrioid carcinoma.

    PubMed

    Yang, Yihua; Jiang, Yan; Jiang, Man; Zhang, Jiamiao; Yang, Bing; She, Yuanping; Wang, Wanxue; Deng, Yan; Ye, Yuan

    2016-04-01

    Endometrial cancer is the most common gynecologic malignancy and about 80% of these cancers are endometrial endometrioid carcinoma (EEC). Previously, we have demonstrated that protocadherin 10 (PCDH10) is a tumor suppressor gene in EEC, and in this study we further explored the molecular mechanisms of PCDH10 in EEC. We first detect the PCDH10 expression in EEC tissues and then investigate the mechanism in two EEC cell lines. The mRNA and protein expression levels were measured by quantitative real time PCR (qRT-PCR) and western blot, respectively; Cell growth was determined by MTS, CCK-8 and colony formation assays; Cell cycle was determined by flow cytometry, and cell apoptosis was examined by flow cytometry and TUNEL assay. The downstream mediator of PCHD10 was confirmed by Topflash luciferase reporter assay. QRT-PCR and western blot results showed that PCDH10 was down-regulated in EEC clinical tissues. Restoration of PCDH10 suppressed cell growth and induced apoptosis in EEC cells. Dishevelled, EGL-10 and Pleckstrin domain containing 1 (DEPDC1) was a potential downstream mediator of PCDH10 as revealed by RNA-sequencing, and mechanistic studies suggested that DEPDC1 is a downstream mediator and promotes cell growth and induces apoptosis in EEC cells. Western blot further showed that PCDH10 restoration activate apoptotic signaling pathway via caspase signaling in both EEC cell lines and EEC clinical tissues. Collectively, our results suggest that PCDH10-DEPDC1-caspase signaling may be a novel regulatory axis in EEC development and it will be of great interest to explore the clinical significance of PCDH10 and DEPDC1 in the future.

  15. 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

  16. 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

  17. TGF-β1 stimulates migration of type II endometrial cancer cells by down-regulating PTEN via activation of SMAD and ERK1/2 signaling pathways.

    PubMed

    Xiong, Siyuan; Cheng, Jung-Chien; Klausen, Christian; Zhao, Jianfang; Leung, Peter C K

    2016-09-20

    PTEN acts as a tumor suppressor primarily by antagonizing the PI3K/AKT signaling pathway. PTEN is frequently mutated in human cancers; however, in type II endometrial cancers its mutation rate is very low. Overexpression of TGF-β1 and its receptors has been reported to correlate with metastasis of human cancers and reduced survival rates. Although TGF-β1 has been shown to regulate PTEN expression through various mechanisms, it is not yet known if the same is true in type II endometrial cancer. In the present study, we show that treatment with TGF-β1 stimulates the migration of two type II endometrial cancer cell lines, KLE and HEC-50. In addition, TGF-β1 treatment down-regulates both mRNA and protein levels of PTEN. Overexpression of PTEN or inhibition of PI3K abolishes TGF-β1-stimulated cell migration. TGF-β1 induces SMAD2/3 phosphorylation and knockdown of common SMAD4 inhibits the suppressive effects of TGF-β1 on PTEN mRNA and protein. Interestingly, TGF-β1 induces ERK1/2 phosphorylation and pre-treatment with a MEK inhibitor attenuates the suppression of PTEN protein, but not mRNA, by TGF-β1. This study provides important insights into the molecular mechanisms mediating TGF-β1-induced down-regulation of PTEN and demonstrates an important role of PTEN in the regulation of type II endometrial cancer cell migration.

  18. TGF-β1 stimulates migration of type II endometrial cancer cells by down-regulating PTEN via activation of SMAD and ERK1/2 signaling pathways

    PubMed Central

    Xiong, Siyuan; Cheng, Jung-Chien; Klausen, Christian; Zhao, Jianfang; Leung, Peter C.K.

    2016-01-01

    PTEN acts as a tumor suppressor primarily by antagonizing the PI3K/AKT signaling pathway. PTEN is frequently mutated in human cancers; however, in type II endometrial cancers its mutation rate is very low. Overexpression of TGF-β1 and its receptors has been reported to correlate with metastasis of human cancers and reduced survival rates. Although TGF-β1 has been shown to regulate PTEN expression through various mechanisms, it is not yet known if the same is true in type II endometrial cancer. In the present study, we show that treatment with TGF-β1 stimulates the migration of two type II endometrial cancer cell lines, KLE and HEC-50. In addition, TGF-β1 treatment down-regulates both mRNA and protein levels of PTEN. Overexpression of PTEN or inhibition of PI3K abolishes TGF-β1-stimulated cell migration. TGF-β1 induces SMAD2/3 phosphorylation and knockdown of common SMAD4 inhibits the suppressive effects of TGF-β1 on PTEN mRNA and protein. Interestingly, TGF-β1 induces ERK1/2 phosphorylation and pre-treatment with a MEK inhibitor attenuates the suppression of PTEN protein, but not mRNA, by TGF-β1. This study provides important insights into the molecular mechanisms mediating TGF-β1-induced down-regulation of PTEN and demonstrates an important role of PTEN in the regulation of type II endometrial cancer cell migration. PMID:27542208

  19. Post-translational regulation of the cleaved fragment of Par-4 in ovarian and endometrial cancer cells

    PubMed Central

    Brasseur, Kevin; Fabi, François; Adam, Pascal; Parent, Sophie; Lessard, Laurent; Asselin, Eric

    2016-01-01

    We recently reported the caspase3-dependent cleavage of Par-4 resulting in the accumulation of a 25kDa cleaved-Par-4 (cl-Par-4) fragment and we investigated in the present study the mechanisms regulating this fragment using cl-Par-4-expressing stable clones derived from ovarian and endometrial cancer cell lines. Cl-Par-4 protein was weakly express in all stable clones despite constitutive expression. However, upon cisplatin treatment, cl-Par-4 levels increased up to 50-fold relative to baseline conditions. Treatment of stable clones with proteasome and translation inhibitors revealed that cisplatin exposure might in fact protect cl-Par-4 from proteasome-dependent degradation. PI3K and MAPK pathways were also implicated as evidenced by an increase of cl-Par-4 in the presence of PI3K inhibitors and a decrease using MAPK inhibitors. Finally using bioinformatics resources, we found diverse datasets showing similar results to those we observed with the proteasome and cl-Par-4 further supporting our data. These new findings add to the complex mechanisms regulating Par-4 expression and activity, and justify further studies addressing the biological significance of this phenomenon in gynaecological cancer cells. PMID:27175591

  20. 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.

  1. Endometrial hyperplasia.

    PubMed

    Mills, Anne M; Longacre, Teri A

    2010-11-01

    Endometrial hyperplasia is a heterogeneous set of pathologic lesions that range from mild, reversible glandular proliferations to direct cancer precursors. These lesions comprise a continuum of morphologic appearances, with the earliest proliferation represented by crowded glands with simple tubular architecture lined by cells resembling proliferative endometrium, whereas advanced proliferations in this continuum are characterized by crowded glands with complex architecture, often containing cells with nuclear atypia resembling low-grade endometrioid adenocarcinoma. The former "early" proliferations may be isolated to an endometrial polyp, but advanced proliferations are generally more diffusely present throughout the endometrium. There are at least three major classification systems for endometrial carcinoma precursor lesions, each of which trend toward overlap at the complex end of the spectrum. Although some classifications are based on a series of molecular genetic alterations (which may or may not translate into biologically or clinically relevant risk lesions), each classification scheme ultimately uses a series of histologic features, usually a combination of architecture and cytology, to establish a diagnosis of hyperplasia. Because different pathologists may apply different histologic criteria for endometrial hyperplasia depending on the classification system used, this article will provide an overview of the classifications used in current daily practice, present the histologic criteria and relative merits of each classification system, and discuss common and not so common causes of misclassification.

  2. Epigenetic regulation of L1CAM in endometrial carcinoma: comparison to cancer–testis (CT-X) antigens

    PubMed Central

    2013-01-01

    Background L1CAM was originally identified as an adhesion molecule involved in neural development. In many human carcinomas L1CAM is over-expressed and is associated with a bad prognosis. We previously reported that L1CAM was absent in the vast majority of endometrioid endometrial carcinomas (ECs) (type 1) but was strongly expressed in the more aggressive serous and clear-cell ECs (termed type 2). The differential regulation of L1CAM in ECs is not well understood. Recent evidence suggests that it can be regulated by epigenetic mechanisms. Here we investigated the role of DNA-methylation of the L1CAM promoter for expression. We also studied the relationship to cancer testis (CT-X) antigens that co-localize with L1CAM on chromosome Xq28, a region that is often activated in human tumors. Methods We used EC cell lines and primary tumor tissues for our analysis. For expression analysis we employed RT-PCR and Western blotting. DNA-Methylation of the L1CAM promoter was determined after bisulfite conversation and DNA sequencing. Tumor tissues were examined by immunohistochemical (IHC) staining. Results We demonstrate that the treatment of L1CAM low/negative expressing EC cell lines with 5′-Azacytidine (5-AzaC) or knock-down of DNMT1 (DNA methyltransferase 1) as well as the HDAC (histone deacetylase) inhibitor Trichostatin A (TSA) up-regulated L1CAM at the mRNA and protein level. The L1CAM gene has two promoter regions with two distinct CpG islands. We observed that the expression of L1CAM correlated with hypermethylation in promoter 1 and 5-AzaC treatment affected the DNA-methylation pattern in this region. The CT-X antigens NY-ESO-1, MAGE-A3 and MAGE-A4 were also strongly up-regulated by 5-AzaC or knock-down of DNMT1 but did not respond to treatment with TSA. Primary EC tumor tissues showed a variable methylation pattern of the L1CAM promoter. No striking differences in promoter methylation were observed between tumor areas with L1CAM expression and those without

  3. Syndecan-1 Acts as an Important Regulator of CXCL1 Expression and Cellular Interaction of Human Endometrial Stromal and Trophoblast Cells

    PubMed Central

    Altergot-Ahmad, Olga; Pour, Sarah Jean; Krüssel, Jan-Steffen; Markert, Udo Rudolf; Fehm, Tanja Natascha; Bielfeld, Alexandra Petra

    2017-01-01

    Successful implantation of the embryo into the human receptive endometrium is substantial for the establishment of a healthy pregnancy. This study focusses on the role of Syndecan-1 at the embryo-maternal interface, the multitasking coreceptor influencing ligand concentration, release and receptor presentation, and cellular morphology. CXC motif ligand 1, being involved in chemotaxis and angiogenesis during implantation, is of special interest as a ligand of Syndecan-1. Human endometrial stromal cells with and without Syndecan-1 knock-down were decidualized and treated with specific inhibitors to evaluate signaling pathways regulating CXC ligand 1 expression. Western blot analyses of MAPK and Wnt members were performed, followed by analysis of spheroid interactions between human endometrial cells and extravillous trophoblast cells. By mimicking embryo contact using IL-1β, we showed less ERK and c-Jun activation by depletion of Syndecan-1 and less Frizzled 4 production as part of the canonical Wnt pathway. Additionally, more beta-catenin was phosphorylated and therefore degraded after depletion of Syndecan-1. Secretion of CXC motif ligand 1 depends on MEK-1 with respect to Syndecan-1. Regarding the interaction of endometrial and trophoblast cells, the spheroid center-to-center distances were smaller after depletion of Syndecan-1. Therefore, Syndecan-1 seems to affect signaling processes relevant to signaling and intercellular interaction at the trophoblast-decidual interface. PMID:28293067

  4. 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

  5. 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.

  6. Nuclear Receptor Co-Regulator Krüppel-like Factor 9 in Human Endometrial Stromal Cell Differentiation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The biological actions of ligand-bound estrogen (E) and progesterone (P) receptors are dependent on coregulator partner proteins. We have identified Krüppel-like Factor 9 (KLF9) as important for E and P actions in endometrial cells. Ablation of KLF9 in mice resulted in subfertility due partly to alt...

  7. From endometrial hyperplasia to endometrial cancer: insight into the biology and possible medical preventive measures.

    PubMed

    Boruban, Melih C; Altundag, Kadri; Kilic, Gokhan S; Blankstein, Josef

    2008-04-01

    Controversies are still seen in the histological differential diagnosis of hyperplasia and well-differentiated endometrial carcinoma. Prediction of endometrial cancer in patients with hyperplasia with atypia, with the available markers has not been reliable yet. Hence these patients require more attention in the clinical management. Endometrial hyperplasia is proliferation of endometrial glands resulting in a higher gland : stroma ratio. Cytological atypia, which may progress to or co-exist with endometrial cancer and other pathological changes, result from estrogen stimulation unopposed by progesterone. Biomarkers whose expression is altered in cases of endometrial hyperplasia or cancer such as progesterone receptor, insulin-like growth factor I, retinaldehyde dehydrogenase type II, and secreted frizzled-related protein 4, seem to be promising to use as early-stage tumor markers. Mutation of PTEN is present in 83% of endometrial adenocarcinoma cases, making it the most frequent early molecular genetic alteration in type 1 endometrial tumors, which are generally associated with hyperplasia. p53 gene mutation is not found in endometrial hyperplasia, but researchers have detected this mutation in 20% of cases of endometrial carcinoma and 90% of cases of serous endometrial tumors. Cyclooxygenase-2 is important in tumorogenic transformation of hyperplasia. Expression of cyclooxygenase-2 decreases apoptosis, increases angiogenesis, and is related to invasiveness. Cyclooxygenase-2 expression increases significantly in cases of well-differentiated endometrial adenocarcinoma. Prostaglandin E2 is known to regulate aromatase gene expression and is the product of cyclooxygenase-2. The data about aromatase inhibitors are promising; in breast cancer patients, treatment with tamoxifen induces uterine abnormalities as early as 3 months after the initiation of therapy. In contrast, these abnormalities are not seen in patients who receive aromatase inhibitors and switched therapy

  8. 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

  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. WNT4 acts downstream of BMP2 and functions via β-catenin signaling pathway to regulate human endometrial stromal cell differentiation.

    PubMed

    Li, Quanxi; Kannan, Athilakshmi; Das, Amrita; Demayo, Franco J; Hornsby, Peter J; Young, Steven L; Taylor, Robert N; Bagchi, Milan K; Bagchi, Indrani C

    2013-01-01

    Differentiation of endometrial stromal cells into decidual cells is a prerequisite for successful embryo implantation. Our previous studies in the mouse have shown that bone morphogenetic protein 2 (BMP2), a morphogen belonging to the TGFβ superfamily, is essential for this differentiation process. BMP2 is markedly induced in human primary endometrial stromal cells (HESCs) as they undergo differentiation in response to steroid hormones and cAMP. The present study was undertaken to identify the BMP2-mediated molecular pathways in primary cultures of HESCs during decidualization. Using gene expression profiling, we identified wingless-related murine mammary tumor virus integration site 4 (WNT4) as a target of BMP2 regulation during decidualization. Attenuation of WNT4 expression in HESCs by small interfering RNA administration greatly reduced BMP2-induced stromal differentiation. Additionally, adenovirus-mediated overexpression of WNT4 in HESCs markedly advanced the differentiation program, indicating that it is a key regulator of decidualization. The stimulatory effect of WNT4 was accompanied by the accumulation of active β-catenin in the nuclei of decidualizing stromal cells, indicating the involvement of the canonical WNT signaling pathway. Functional inhibition of WNT4/β-catenin pathway by Dickkopf-1, an inhibitor of the canonical WNT signaling, or small interfering RNA-mediated silencing of β-catenin expression, greatly reduced the BMP2- and WNT4-induced decidualization. Gene expression profiling revealed that Forkhead box protein O1, a forkhead family transcription factor and previously reported regulator of HESC differentiation, is a common downstream mediator of both BMP2 and WNT4 signaling. Taken together, these studies uncovered a linear pathway involving BMP2, WNT4/β-catenin, and Forkhead box protein O1 that operates in human endometrium to critically control decidualization.

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

    ClinicalTrials.gov

    2017-01-20

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

  12. Dose-dependent insulin regulation of insulin-like growth factor binding protein-1 in human endometrial stromal cells is mediated by distinct signaling pathways.

    PubMed

    Lathi, R B; Hess, A P; Tulac, S; Nayak, N R; Conti, M; Giudice, L C

    2005-03-01

    IGF binding protein-1 (IGFBP-1) is a major product of decidualized human endometrial stromal cells and decidua, and as a modulator of IGF action and/or by independent mechanisms, it regulates cell growth and differentiation and embryonic implantation in these tissues. IGFBP-1 secretion is primarily stimulated by progesterone and cAMP and is inhibited by insulin and IGFs. The signaling pathways mediating the latter are not well defined, and the current study was conducted to determine which pathways mediate the effects of insulin on IGFBP-1 mRNA and protein expression by human endometrial stromal cells decidualized in vitro by progesterone. Cells were cultured and treated with different combinations of insulin; wortmannin, an inhibitor of the phosphatidylinositide-3-kinase (PI3-kinase) pathway; and PD98059, an inhibitor of the MAPK pathway. IGFBP-1 mRNA was determined by real-time PCR, and protein secretion in the conditioned medium was measured by ELISA. Activation of the PI3-kinase and the MAPK pathways was assessed by the detection of phosphorylated AKT and ERK in Western blots, respectively. Insulin inhibited IGFBP-1 mRNA and protein secretion in a dose-dependent fashion, with an ED(50) for the latter 0.127 ng/ml (21.6 pm). Inhibitor studies revealed that at low doses, insulin acts through the PI3-kinase pathway, whereas at higher levels it also activates the MAPK pathway in the inhibition of IGFBP-1. The data demonstrate that human endometrium is a target for insulin action in the regulation of IGFBP-1. At physiological levels insulin likely plays a homeostatic role for energy metabolism in the endometrium, and in hyperinsulinemic states, insulin action on the endometrium may activate cellular mitosis via the MAPK pathway and perhaps predispose this tissue to hyperplasia and/or cancer.

  13. 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

  14. 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

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

    ClinicalTrials.gov

    2017-01-31

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

  16. Nintedanib in Treating Patients With Recurrent or Persistent Endometrial Cancer

    ClinicalTrials.gov

    2016-10-26

    Endometrial Adenocarcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Mucinous Adenocarcinoma; Endometrial Serous Adenocarcinoma; Endometrial Squamous Cell Carcinoma; Endometrial Transitional Cell Carcinoma; Endometrial Undifferentiated Carcinoma; Malignant Uterine Corpus Mixed Epithelial and Mesenchymal Neoplasm; Recurrent Uterine Corpus Carcinoma

  17. Expression of leptin receptor in endometrial biopsies of endometrial and ovarian cancer patients

    PubMed Central

    MÉNDEZ-LÓPEZ, LUIS FERNANDO; DÁVILA-RODRÍGUEZ, MARTHA IMELDA; ZAVALA-POMPA, ANGEL; TORRES-LÓPEZ, ERNESTO; GONZÁLEZ-MARTÍNEZ, BLANCA EDELIA; LÓPEZ-CABANILLAS-LOMELÍ, MANUEL

    2013-01-01

    The adipokine leptin plays a critical role in the regulation of reproductive function and there has been growing interest in its potential role in the development of cancers in which obesity is an established risk factor. Serum leptin levels were found to be higher in patients diagnosed with endometrial and ovarian cancer compared to those observed in healthy individuals. This study was conducted to determine the expression of the leptin receptor (Ob-R) in endometrial biopsies of patients diagnosed with endometrial and ovarian cancer. In this preliminary study, immunohistochemistry (IHC) and the color deconvolution method were used to assess the expression levels of the Ob-R protein in three groups of endometrial tissue: one from patients diagnosed with endometrioid endometrial carcinoma, one from patients diagnosed with ovarian cancer and one from individuals without any diagnosed gynecologic disease (control group). Our results demonstrated that the highest expression of Ob-R protein in endometrial biopsies was detected in the ovarian cancer group (P=0.000). This finding suggests that changes in Ob-R expression may be assessed through the measurement of the optical density of endometrial biopsies and may become a useful tool in preventive screening, particularly for ovarian cancer. PMID:24649005

  18. 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

  19. GnRH antagonists may affect endometrial receptivity

    PubMed Central

    Rackow, Beth W.; Kliman, Harvey J.; Taylor, Hugh S.

    2009-01-01

    Study objective HOXA10 is an essential regulator of endometrial receptivity. To determine the effect of gonadotropin releasing hormone (GnRH) antagonists on endometrial receptivity we assessed endometrial HOXA10 expression in GnRH antagonist, GnRH agonist, and natural cycles. Design Prospective case-control study Setting University academic medical center Patients Nineteen subjects were included: 12 subjects underwent controlled ovarian hyperstimulation (COH) with recombinant follicle stimulating hormone (rFSH) and used either a GnRH antagonist or a GnRH agonist; 7 control subjects underwent natural cycles. Interventions Pipelle endometrial biopsies were obtained 11 days after human chorionic gonadotropin (hCG) administration or spontaneous luteinizing hormone (LH) surge in untreated cycles, respectively. Immunohistochemistry was used to assess HOXA10 protein expression in endometrial glands and stroma. Main outcome measure(s) Endometrial HOXA10 protein expression Results HOXA10 expression was significantly decreased in endometrial stromal cells in GnRH antagonist treated cycles compared with GnRH agonist treated cycles or natural cycle controls. There was no significant difference in glandular cell HOXA10 expression among the three groups. Conclusions Use of GnRH antagonists may be associated with impaired HOXA10 expression in endometrial stromal cells, and thus may affect endometrial receptivity. PMID:18410932

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

    PubMed

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

    2015-10-13

    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 B (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.

  1. 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…

  2. 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

  3. Stages of Endometrial Cancer

    MedlinePlus

    ... Stage II endometrial cancer. Cancer has spread into connective tissue of the cervix, but has not spread outside ... uterus. In stage II , cancer has spread into connective tissue of the cervix , but has not spread outside ...

  4. Endometrial Cancer Prevention

    MedlinePlus

    ... is the most common invasive cancer of the female reproductive system. Endometrial cancer is diagnosed most often ... body. It helps the body develop and maintain female sex characteristics. Estrogen can affect the growth of ...

  5. Endometrial Ablation for Menorrhagia

    PubMed Central

    Sanders, Barry H.

    1992-01-01

    Endometrial ablation is a relatively new treatment for patients with persistent menorrhagia. The procedure can be performed by either laser photocoagulation or electrocoagulation; both have a very low risk of complication. Generally, less than 24 hours of hospitalization is required and return to normal activities, including work, is almost immediate. Endometrial ablation is likely to become a mainstay of treatment for menorrhagia as the technology and training become more readily available. PMID:21229128

  6. Stretch magnitude- and frequency-dependent cyclooxygenase 2 and prostaglandin E2 up-regulation in human endometrial stromal cells: possible implications in endometriosis.

    PubMed

    Li, Xiaochuan; Gong, Xianghui; Zhu, Lan; Leng, Jinhua; Fan, Qingbo; Sun, Dawei; Lang, Jinghe; Fan, Yubo

    2012-11-01

    Endometriosis, with a prevalence rate ranging from 6% to 10%, is the major contributor to pelvic pain and subfertility, and considerably reduces the quality of life in affected women. However, the pathogenesis of this disease remains largely unknown. The present study aimed to uncover the role of hyperperistalsis in the pathogenesis of endometriosis, by exploring the response of human endometrial stromal cells (ESCs) to the cyclic stretch in vitro. ESCs isolated from 18 different endometrium biopsies undergoing hysterectomy for myoma were subjected to uniaxial cyclic stretches with different magnitude and frequency using the Uniaxial Tension System. Expression of cyclooxygenase-2 (COX-2) and microsomal prostaglandin E2 synthase-1 (mPGES-1) in stretched and unstretched ESCs were assessed by realtime quantitative polymerase chain reaction and Western blot. Production of prostaglandin E2 (PGE(2)) in the culture medium was measured by enzyme-linked immunosorbent assay. The cyclic stretch mimicking hyperperistalsis in endometriosis (5% elongation at 4 cycles/min) stimulated quick up-regulations of COX-2 and mPGES-1 simultaneously on both transcriptional and translational levels, and delayed PGE(2) overproduction was also noted in ESCs. As the stretch magnitude or frequency increased, so did overexpression of COX-2 and PGE(2) (P < 0.05). By contrast, the cyclic stretch mimicking physiological peristalsis (3% elongation at 2 cycles/min) did not induce significant COX-2, mPGES-1 or PGE(2) production within 12 h. Both COX-2 and mPEGS-1 are PGE(2) synthases, and the aberrant COX-2 and PGE(2) production play important roles in the pathogenesis of endometriosis. Therefore, the present findings revealed that increased stretch stimuli from the hyperperistalsis of endometriosis were capable of causing the aberrant COX-2 and PGE(2) expression in the endometrium by mechanotransduction, in a magnitude and frequency-dependent manner. It implied possible roles of hyperperistalsis in

  7. 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

  8. 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…

  9. INCIDENCE OF ENDOMETRIAL HYPERPLASIA

    PubMed Central

    REED, Susan D.; NEWTON, Katherine M.; CLINTON, Walter L.; EPPLEIN, Meira; GARCIA, Rochelle; ALLISON, Kimberly; VOIGT, Lynda F.; Weiss, Noel S.

    2009-01-01

    Objective Estimate age-specific incidence of endometrial hyperplasia: simple, complex, and atypical, in order of increasing likelihood of progression to carcinoma. Study design Women ages 18–90 years with endometrial pathology specimens (1985–2003) at a large integrated health plan were identified using automated data. Incidence rates were obtained by dividing the number of cases by the estimated number of female health plan enrollees who retained a uterus. Results Endometrial hyperplasia peak incidence was: simple-142/100,000 woman-years, complex-213/100,000 woman-years, both in the early 50s; and atypical-56/100,000 woman-years in the early 60s. Age-adjusted incidence decreased over the study period, especially for atypical hyperplasia. Conclusions Endometrial hyperplasia incidence without and with atypia peaks in the early postmenopausal years and in the early 60s, respectively. Given that some cases of endometrial hyperplasia likely go undiagnosed, the figures provided should be viewed as minimum estimates of the true incidence. PMID:19393600

  10. 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.

  11. Stromal p16 expression is significantly increased in endometrial carcinoma.

    PubMed

    Yoon, Gun; Koh, Chang Won; Yoon, Nara; Kim, Ji-Ye; Kim, Hyun-Soo

    2017-01-17

    p16 is a negative regulator of cell proliferation and is considered a tumor suppressor protein. Alterations in p16 protein expression are associated with tumor development and progression. However, the p16 expression status in the peritumoral stroma has not been investigated in the endometrium. Therefore, we evaluated stromal p16 expression in different types of endometrial lesions using immunohistochemistry. Differences in the p16 expression status according to the degree of malignancy and histological type were analyzed. This study included 62, 26, and 36 cases of benign, precancerous, and malignant endometrial lesions, respectively. Most benign lesions showed negative or weak expression, whereas precancerous lesions showed a variable degree of staining proportion and intensity. Atypical hyperplasia/endometrial intraepithelial neoplasia (AH/EIN) and serous endometrial intraepithelial carcinoma (SEIC) had significantly higher stromal p16 expression levels than benign lesions. Endometrioid carcinoma (EC), serous carcinoma (SC), and carcinosarcoma showed significantly elevated stromal p16 expression levels compared with benign and precancerous lesions. In addition, there were significant differences in stromal p16 expression between AH/EIN and SEIC and between EC and SC. In contrast, differences in stromal p16 expression among nonpathological endometrium, atrophic endometrium, endometrial polyp, and hyperplasia without atypia were not statistically significant. Our observations suggest that stromal p16 expression is involved in the development and progression of endometrial carcinoma, and raise the possibility that p16 overexpression in the peritumoral stroma is associated with aggressive oncogenic behavior of endometrial SC.

  12. Dicer1 dysfunction promotes stemness and aggression in endometrial carcinoma.

    PubMed

    Wang, Xiao-Jun; Jiang, Fei-Zhou; Tong, Huan; Ke, Jie-Qi; Li, Yi-Ran; Zhang, Hui-Lin; Yan, Xiao-Fang; Wang, Fang-Yuan; Wan, Xiao-Ping

    2017-04-01

    Endometrial carcinoma is one of the most common gynecological malignancies, but the molecular events involved in the development and progression of endometrial carcinoma remain unclear. Dicer1 and cancer stem cells play important roles in cell motility and survival. This study investigated the role of the let-7 family and Dicer1 in the stemness of endometrial carcinoma cells. We profiled Dicer1 expression in clinical samples and explored its relationship with stem cell-associated markers and clinical parameters. We showed that Dicer1 dysfunction leads to the enrichment of tumor stemness features and tumor aggression both in vitro and in vivo. We also identified the mechanism related to this potential tumor-predisposing phenotype: loss of Dicer1 induced abnormal expression of the let-7 family, which comprises well-known tumor suppressors, thus regulating stemness in endometrial carcinoma cells.

  13. 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…

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

    ClinicalTrials.gov

    2016-10-26

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

  15. 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

  16. Recent Advances in Endometrial Cancer

    PubMed Central

    Tran, Arthur-Quan; Gehrig, Paola

    2017-01-01

    Endometrial cancer is the most common gynecologic malignancy in the United States, with yearly rates continuing to increase. Most women present with early stage disease; however, advanced disease carries a grave prognosis. As a result, novel therapies are currently under investigation for the treatment of endometrial cancer. These advances include a better understanding of the genetic basis surrounding the development of endometrial cancer, novel surgical therapies, and new molecular targets for the treatment of this disease. This review explores the literature regarding these advancements in endometrial cancer. PMID:28184290

  17. 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…

  18. 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…

  19. Camp Minden Dialogue

    EPA Pesticide Factsheets

    The Minden Dialogue Committee is made up of a group of individual volunteer citizens, community leaders, local and statewide organizations, scientists, elected officials and state representatives that will look at alternatives to address onsite materials.

  20. Correlation between NDRG1 and PTEN expression in endometrial carcinoma.

    PubMed

    Chen, Jiawei; Li, Shuxia; Yang, Zhaorui; Lu, Guangzhong; Hu, Honghui

    2008-04-01

    N-myc Downstream-Regulated Gene 1 (NDRG1) is known as a differentiation-related gene that plays important roles in cell differentiation, organ formation, and embryonic development. NDRG1 has recently been shown to be associated with carcinogenesis and tumor progression in a wide variety of tumors. Phosphatase and tensin homolog deleted from chromosome (PTEN), a phosphatase and tensin homolog located on chromosome 10, is shown to be a tumor suppressor and is often mutated or deleted in various tumor cells, particularly in endometrial carcinoma. Using an immunohistochemical approach, we investigated the expression of NDRG1 and PTEN in normal endometrium, atypical hyperplasia, and endometrial carcinoma. All tumor tissues harvested in this study were derived from endometrioid carcinoma Type I, that were estrogen-related. Our results demonstrate that the expression of NDRG1 was up-regulated in 5/40 (12.5%), 18/34 (52.94%), and 86/103 (83.5%) normal endometrium, atypical hyperplasia, and endometrial carcinoma cases, respectively (P < 0.01), while in 6/40 (15%), 20/34 (58.82%), and 89/103 (86.41%) normal endometrium, atypical hyperplasia, and endometrial carcinoma cases, respectively. PTEN expression was significantly decreased (P < 0.01). Statistical analyzes demonstrated a positive correlation between NDRG1 up-regulation and PTEN down-regulation (P < 0.01). The expression of NDRG1 had no correlation with the differentiation degree of the tumor cells, lymph-node metastasis, and/or abdominal cavity implantation (P > 0.05). Our results indicated that development of endometrial carcinoma is associated with an overexpression of NDRG1 and the loss of PTEN expression. Identification of changes in the NDRG1 and PTEN expression may be a significant diagnostic tool for the early detection of endometrial carcinoma.

  1. Endometrial Intraepithelial Neoplasia (EIN) in endometrial biopsy specimens categorized by the 1994 World Health Organization classification for endometrial hyperplasia.

    PubMed

    Li, Xiao-Chao; Song, Wen-Jing

    2013-01-01

    Our study is to determine the presence of endometrial intraepithelial neoplasia (EIN) in endometrial biopsy specimens classified by the 1994 World Health Organization (WHO) criteria for endometrial hyperplasia. Endometrial biopsy specimens that were stained with hematoxylin and eosin (HE) were examined and categorized by the WHO 1994 criteria and for the presence of EIN as defined by the International Endometrial Collaborative Group. β-catenin expression was examined by immunohistochemistry. A total of 474 cases of HE stained endometrial biopsy tissues were reviewed. There were 379 cases of simple endometrial hyperplasia, 16 with simple atypical endometrial hyperplasia, 48 with complex endometrial hyperplasia, and 31 with complex atypical endometrial hyperplasia. Among the 474 endometrial hyperplasia cases, there were 46 (9.7%) that were classified as EIN. Of these 46 cases, 11(2.9%) were classified as simple endometrial hyperplasia, 1 (6.3%) as simple atypical endometrial hyperplasia, 6 (12.5%) as complex endometrial hyperplasia, and 28 (90.3%) as complex atypical endometrial hyperplasia. EIN was associated with a higher rate of β-catenin positivity than endometrium classified as benign hyperplasia (72% vs. 22.5%, respectively, P < 0.001), but a lower rate than endometrial adenocarcinoma (72% vs. 96.2%, respectively, P < 0.001). In benign endometrial hyperplasia, high β-catenin expression was noted in the cell membranes, whereas in EIN and endometrial adenocarcinoma high expression was noted in the cytoplasm. In conclusion, EIN is more accurate than the WHO classification for the diagnosis of precancerous lesions of the endometrium.

  2. Epigenetics and genetics in endometrial cancer: new carcinogenic mechanisms and relationship with clinical practice.

    PubMed

    Banno, Kouji; Kisu, Iori; Yanokura, Megumi; Masuda, Kenta; Ueki, Arisa; Kobayashi, Yusuke; Susumu, Nobuyuki; Aoki, Daisuke

    2012-04-01

    Endometrial cancer is the seventh most common cancer worldwide among females. An increased incidence and a younger age of patients are also predicted to occur, and therefore elucidation of the pathological mechanisms is important. However, several aspects of the mechanism of carcinogenesis in the endometrium remain unclear. Associations with genetic mutations of cancer-related genes have been shown, but these do not provide a complete explanation. Therefore, epigenetic mechanisms have been examined. Silencing of genes by DNA hypermethylation, hereditary epimutation of DNA mismatch repair genes and regulation of gene expression by miRNAs may underlie carcinogenesis in endometrial cancer. New therapies include targeting epigenetic changes using histone deacetylase inhibitors. Some cases of endometrial cancer may also be hereditary. Thus, patients with Lynch syndrome which is a hereditary disease, have a higher risk for developing endometrial cancer than the general population. Identification of such disease-related genes may contribute to early detection and prevention of endometrial cancer.

  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. Overactive mTOR signaling leads to endometrial hyperplasia in aged women and mice.

    PubMed

    Bajwa, Preety; Nielsen, Sarah; Lombard, Janine M; Rassam, Loui; Nahar, Pravin; Rueda, Bo R; Wilkinson, J Erby; Miller, Richard A; Tanwar, Pradeep S

    2017-01-31

    During aging, uncontrolled epithelial cell proliferation in the uterus results in endometrial hyperplasia and/or cancer development. The mTOR signaling pathway is one of the major regulators of aging as suppression of this pathway prolongs lifespan in model organisms. Genetic alterations in this pathway via mutations and/or amplifications are often encountered in endometrial cancers. However, the exact contribution of mTOR signaling and uterine aging to endometrial pathologies is currently unclear. This study examined the role of mTOR signaling in uterine aging and its implications in the development of endometrial hyperplasia. The hyperplastic endometrium of both postmenopausal women and aged mice exhibited elevated mTOR activity as seen with increased expression of the pS6 protein. Analysis of uteri from Pten heterozygous and Pten overexpressing mice further confirmed that over-activation of mTOR signaling leads to endometrial hyperplasia. Pharmacological inhibition of mTOR signaling using rapamycin treatment suppressed endometrial hyperplasia in aged mice. Furthermore, treatment with mTOR inhibitors reduced colony size and proliferation of a PTEN negative endometrial cancer cell line in 3D culture. Collectively, this study suggests that hyperactivation of the mTOR pathway is involved in the development of endometrial hyperplasia in aged women and mice.

  5. ZEB1 overexpression associated with E-cadherin and microRNA-200 downregulation is characteristic of undifferentiated endometrial carcinoma.

    PubMed

    Romero-Pérez, Laura; López-García, M Ángeles; Díaz-Martín, Juan; Biscuola, Michele; Castilla, M Ángeles; Tafe, Laura J; Garg, Karuna; Oliva, Esther; Matias-Guiu, Xavier; Soslow, Robert A; Palacios, José

    2013-11-01

    Undifferentiated endometrial carcinomas are very aggressive high-grade endometrial carcinomas that are frequently under-recognized. This study aimed to analyze the molecular alterations underlying the development of these endometrial carcinomas, focusing on those related to dedifferentiation. We assessed a series of 120 tumors: 57 grade 1 and 2 endometrioid endometrial carcinomas, 15 grade 3 endometrioid endometrial carcinomas, 27 endometrial serous carcinomas, and 21 undifferentiated endometrial carcinomas. We found a high frequency of DNA mismatch repair deficiency (38%) and moderate rate of p53 overexpression (∼33%) in undifferentiated carcinomas. In contrast to the characteristic endometrioid phenotype, there was a dramatic downregulation of E-cadherin expression in the undifferentiated subtype. Quantitative methylation studies dismissed CDH1 promoter hypermethylation as the mechanism responsible for this change in gene expression, while immunohistochemistry revealed that the E-cadherin repressor ZEB1 was frequently overexpressed (62%) in undifferentiated endometrial carcinomas. This finding was accompanied by a sharp downregulation in the expression of the miR-200 family of microRNAs, well-known targets of ZEB1. Furthermore, there was enhanced expression of epithelial-to-mesenchymal transition markers in undifferentiated endometrial carcinomas, such as N-cadherin, cytoplasmic p120, and osteonectin. In addition, HMGA2, a regulator of epithelial-to-mesenchymal transition that is expressed in aggressive endometrial tumors, such as endometrial serous carcinomas and carcinosarcomas, was expressed in >20% of undifferentiated carcinomas. These results suggest that ZEB1 overexpression, associated with E-cadherin and miR-200s downregulation, and the expression of mesenchymal markers might enhance the metastatic potential of undifferentiated endometrial carcinomas, leading to a poor prognosis. In addition, our observations suggest that the immnohistochemical analysis

  6. 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.

  7. Treatment Option Overview (Endometrial Cancer)

    MedlinePlus

    ... Stage II endometrial cancer. Cancer has spread into connective tissue of the cervix, but has not spread outside ... uterus. In stage II , cancer has spread into connective tissue of the cervix , but has not spread outside ...

  8. General Information About Endometrial Cancer

    MedlinePlus

    ... Stage II endometrial cancer. Cancer has spread into connective tissue of the cervix, but has not spread outside ... uterus. In stage II , cancer has spread into connective tissue of the cervix , but has not spread outside ...

  9. Progesterone Receptor Action in Leiomyoma and Endometrial Cancer

    PubMed Central

    Kim, J. Julie; Sefton, Elizabeth C.; Bulun, Serdar E.

    2013-01-01

    Progesterone is a key hormone in the regulation of uterine function. In the normal physiological context, progesterone is primarily involved in remodeling of the endometrium and maintaining a quiescent myometrium. When pathologies of the uterus develop, specifically, endometrial cancer and uterine leiomyoma, response to progesterone is usually altered. Progesterone acts through mainly two isoforms of the progesterone receptor (PR), PRA and PRB which have been reported to exhibit different transcriptional activities. Studies examining the expression and function of the PRs in the normal endometrium and myometrium as well as in endometrial cancer and uterine leiomyoma are summarized here. The clinical use of progestins and the transcriptional activity of the PR on genes specific to endometrial cancer and leiomyoma are described. An increased understanding of the differential expression of PRs and response to progesterone in these two diseases is critical in order to develop more efficient and targeted therapies. PMID:20374701

  10. USP14 is a predictor of recurrence in endometrial cancer and a molecular target for endometrial cancer treatment

    PubMed Central

    Mooneyham, Ashley; Mullany, Sally; Zhao, Xianda; Shahi, Maryam; Richter, James; Klein, Molly; Chen, Liqiang; Ding, Rui; Konecny, Gottfried; Kommoss, Stefan; Winterhoff, Boris; Ghebre, Rahel; Bazzaro, Martina

    2016-01-01

    Endometrial adenocarcinoma is the most common gynecologic malignancy in the United States. Most endometrial cancer cases are diagnosed at an early stage and have good prognosis. Unfortunately a subset of patients with early stage and low grade disease experience recurrence for reasons that remain unclear. Recurrence is often accompanied by chemoresistance and high mortality. Deubiquitinating enzymes (DUBs) are key components of the ubiquitin-dependent protein degradation pathway and act as master regulators in a number of metabolic processes including cell growth, differentiation, and apoptosis. DUBs have been shown to be upregulated in a number of human cancers and their aberrant activity has been linked to cancer progression, initiation and onset of chemoresistance. Thus, selective inhibition of DUBs has been proposed as a targeted therapy for cancer treatment. This study suggests the DUB USP14 as a promising biomarker for stratifying endometrial cancer patients at diagnosis based on their risk of recurrence. Further USP14 is expressed along with the marker of proliferation Ki67 in endometrial cancer cells in situ. Lastly, pharmacological targeting of USP14 with the FDA approved small-molecule inhibitor VLX1570, decreases cell viability in chemotherapy resistant endometrial cancer cells with a mechanism consistent with cell cycle arrest and caspase-3 mediated apoptosis. PMID:27121063

  11. USP14 is a predictor of recurrence in endometrial cancer and a molecular target for endometrial cancer treatment.

    PubMed

    Vogel, Rachel Isaksson; Pulver, Tanya; Heilmann, Wiebke; Mooneyham, Ashley; Mullany, Sally; Zhao, Xianda; Shahi, Maryam; Richter, James; Klein, Molly; Chen, Liqiang; Ding, Rui; Konecny, Gottfried; Kommoss, Stefan; Winterhoff, Boris; Ghebre, Rahel; Bazzaro, Martina

    2016-05-24

    Endometrial adenocarcinoma is the most common gynecologic malignancy in the United States. Most endometrial cancer cases are diagnosed at an early stage and have good prognosis. Unfortunately a subset of patients with early stage and low grade disease experience recurrence for reasons that remain unclear. Recurrence is often accompanied by chemoresistance and high mortality.Deubiquitinating enzymes (DUBs) are key components of the ubiquitin-dependent protein degradation pathway and act as master regulators in a number of metabolic processes including cell growth, differentiation, and apoptosis. DUBs have been shown to be upregulated in a number of human cancers and their aberrant activity has been linked to cancer progression, initiation and onset of chemoresistance. Thus, selective inhibition of DUBs has been proposed as a targeted therapy for cancer treatment.This study suggests the DUB USP14 as a promising biomarker for stratifying endometrial cancer patients at diagnosis based on their risk of recurrence. Further USP14 is expressed along with the marker of proliferation Ki67 in endometrial cancer cells in situ. Lastly, pharmacological targeting of USP14 with the FDA approved small-molecule inhibitor VLX1570, decreases cell viability in chemotherapy resistant endometrial cancer cells with a mechanism consistent with cell cycle arrest and caspase-3 mediated apoptosis.

  12. Narrative, dialogue, and dissociation.

    PubMed

    Gedo, Paul M

    2014-02-01

    This paper explores dissociative phenomena as disruptions of dialogue between persons, and disruptions of internal narratives. A dissociating patient temporarily loses ability to convey his or her inner experience to the therapist. The disconnection between dialogue and internal experience can mislead both participants, or distract them from underlying connotations. Dissociation also disrupts the patient's sense of internal coherence and internal conversation. Dissociation represents a regression to an early, preverbal mode of (internal and external) communication. The challenge for the dyad is to restore dialogue and then to discern the multiply determined meanings of the dissociative communication. This therapeutic work allows the patient to achieve a more coherent sense of self and of his or her life course.

  13. 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…

  14. 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…

  15. 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…

  16. Dialogues in Language Teaching

    ERIC Educational Resources Information Center

    Ockenden, Michael

    1976-01-01

    Distinguishes between structure-oriented and situational dialog, suggesting methods and materials. The following are recommended: Jerrem and Skutznik, "Conversation Exercises in Everyday English" (Longman); M. Ockenden, "Situational Dialogues" (Longman); Jupp, Milne and Plowright, "Talk English" (Heineman); and M. Underwood, "Listen to This"…

  17. 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)

  18. 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…

  19. 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

  20. Intercultural Dialogue: Cultural Dialogues of Equals or Cultural Dialogues of Unequals?

    ERIC Educational Resources Information Center

    Igbino, John

    2011-01-01

    This article has two aims. The first aim of the article is to show some emerging problems and questions facing intercultural dialogue. This involves a critique of intercultural dialogue by situating it within emerging models of cultural change. The second aim of the article is to show alternative approaches to cultural dialogues. This involves the…

  1. Euthanasia—a dialogue

    PubMed Central

    Berry, P.

    2000-01-01

    A terminally ill man requests that his life be brought to a peaceful end by the doctor overseeing his care. The doctor, an atheist, regretfully declines. The patient, unsatisfied by the answer and increasingly desperate for relief, presses the doctor for an explanation. During the ensuing dialogue the philosophical, ethical and emotional arguments brought to bear by both the doctor and the patient are dissected. Key Words: Euthanasia • physician-assisted suicide • autonomy • empathy • end of life PMID:11055041

  2. ATM may be a protective factor in endometrial carcinogenesis with the progesterone pathway.

    PubMed

    Shan, Weiwei; Wang, Chao; Zhang, Zhenbo; Luo, Xuezhen; Ning, Chengcheng; Yu, Yinhua; Feng, Youji; Gu, Chao; Chen, Xiaojun

    2015-03-01

    The purpose of the study was to explore the role and mechanism of ataxia-telangiectasia mutated (ATM) protein in endometrial carcinogenesis. A reverse-phase protein array (RPPA) was used to analyze the expression of ATM signal pathway proteins in Ishikawa and progesterone-insensitive Ishikawa. ATM expression was detected in endometrium specimens by immunohistochemistry, including 8 cases with proliferative endometrium, 6 cases with secretory endometrium, 10 cases with simple hyperplasia (SH), 13 cases of complex hyperplasia (CH), 11 cases of endometrial atypical hyperplasia (EAH), and 83 cases with type I endometrial cancer. The relationship between ATM expression and other clinicopathological indicators was also examined in type I endometrial cancer patients. The mechanisms of ATM were explored in vitro with the endometrial cell lines Ishikawa and RL95-2. A cell counting kit-8 (CCK-8) test and Western blot analysis were performed to test proliferation and protein expression. Statistical analysis was performed with SPSS19.0. The significance level was set at 0.05. ATM was increased with medroxyprogesterone acetate (MPA) stimulation in Ishikawa in RPPA. ATM expression gradually decreased in endometrial hyperplasic lesions compared with the normal proliferative and secretory endometrium and was the lowest in type I endometrial cancer. ATM expression was negatively correlated with pathological grades in type I endometrial cancer. In vitro, ATM silencing retarded proliferation inhibition in Ishikawa and RL95-2 treated with MPA. ATM silencing could down-regulate the MPA-stimulated signal proteins, including Chk2, P53, and caspase-3 in vitro. MPA might exert its role through activating the ATM-associated pathway, ATM-Chk2-P53-caspase-3 (active), preserving normal endometrium and protecting it from malignancies. ATM might be a promising indicator for endometrial hyperplasia and cancer.

  3. 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.

  4. Pesticide Program Dialogue Committee (PPDC)

    EPA Pesticide Factsheets

    The Pesticide Program Dialogue Committee, a permanent, broadly representative advisory committee, meets with EPA on a regular basis to discuss pesticide regulatory, policy, and program implementation issues.

  5. 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

  6. Dialogue as Data in Learning Analytics for Productive Educational Dialogue

    ERIC Educational Resources Information Center

    Knight, Simon; Littleton, Karen

    2015-01-01

    This paper provides a novel, conceptually driven stance on the state of the contemporary analytic challenges faced in the treatment of dialogue as a form of data across on- and offline sites of learning. In prior research, preliminary steps have been taken to detect occurrences of such dialogue using automated analysis techniques. Such advances…

  7. 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.

  8. Endometrial thickness predicts endometrial hyperplasia in patients with polycystic ovary syndrome.

    PubMed

    McCormick, Betsy A; Wilburn, Rochelle D; Thomas, Michael A; Williams, Daniel B; Maxwell, Rose; Aubuchon, Mira

    2011-06-30

    Body mass index is predictive of sonographic endometrial stripe thickness, which in turn is predictive of endometrial hyperplasia in patients with polycystic ovary syndrome. For every 1-mm increase in endometrial stripe, the odds ratio of hyperplasia increased by 1.48 (95% confidence interval, 1.04-2.10).

  9. 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...

  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. Alignment in Second Language Dialogue

    ERIC Educational Resources Information Center

    Costa, Albert; Pickering, Martin; Sorace, Antonella

    2008-01-01

    This paper considers the nature of second language dialogues, involving at least one non-native (L2) speaker. We assume that dialogue is characterised by a process in which interlocutors develop similar mental states to each other (Pickering & Garrod, 2004). We first consider various means in which interlocutors align their mental states, and…

  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…

  13. A proposed model for endometrial serous carcinogenesis.

    PubMed

    Zheng, Wenxin; Xiang, Li; Fadare, Oluwole; Kong, Beihua

    2011-01-01

    Endometrial serous carcinomas constitute no more than 10% of endometrial adenocarcinomas, but frequently present at an advanced stage and have a significantly worse prognosis than the more common low-grade and intermediate-grade endometrioid adenocarcinomas. The neoplasm's potential for rapid tumor progression and the high mortality that is associated with advanced-stage disease underscore the importance of understanding endometrial serous carcinogenesis so that its precancers can be diagnosed and an effective therapeutic intervention can be administered. In this study, the authors summarize the current state of knowledge on endometrial serous carcinogenesis and propose a model for its development based on recent work from our group and published data from other researchers. In this model, endometrial serous carcinoma arises predominantly in the resting endometrium, manifesting first as p53 immunoreactive, morphologically normal endometrial cells (p53 signatures), evolving to endometrial glandular dysplasia (which is the first morphologically identifiable precursor lesion), then to serous endometrial intraepithelial carcinoma (a carcinoma with a noninvasive growth pattern in the uterus but which is not infrequently associated with extrauterine disease), and finally into fully developed serous carcinoma. Endometrial glandular dysplasia is a lesion, which can be diagnosed by routine microscopic evaluation, whose ablation or removal may potentially offer the opportunity to prevent the development of the associated malignancy. The diagnostic criteria, practical applicability, and evidentiary basis for the delineation of this lesion are studied.

  14. Hypertriglyceridemia is Frequent in Endometrial Cancer Survivors

    PubMed Central

    Hirasawa, Akira; Makita, Kazuya; Akahane, Tomoko; Yokota, Megumi; Yamagami, Wataru; Banno, Kouji; Susumu, Nobuyuki; Aoki, Daisuke

    2013-01-01

    Objective Previous studies have reported an association between endometrial cancer and the risk of metabolic syndrome; however, the pattern of endometrial cancer-associated dyslipidemia is not well understood. The standard therapy for endometrial cancer is total abdominal hysterectomy and bilateral salpingo-oophorectomy. Premenopausal bilateral salpingo-oophorectomy may cause adverse events, including dyslipidemia. Gynecologists have to care dyslipidemia in endometrial cancer survivors at cancer follow-up clinic. Methods This study included 693 patients who had undergone bilateral salpingo-oophorectomy, and included 412 women with incident endometrial cancer and 281 controls. We divided the patients into two categories according to whether they had a premenopausal or postmenopausal bilateral oophorectomy. Serum lipid levels were measured and statistically analyzed. Results Hypertriglyceridemia was statistically more frequent in patients who had undergone bilateral salpingo-oophorectomy both before and after menopause than in the corresponding non-endometrial cancer controls. High levels of low-density lipoprotein cholesterol and a high low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio were statistically more frequent in patients who had undergone bilateral salpingo-oophorectomy before menopause than in non-endometrial cancer controls. Conclusions Our report highlights the importance of the relationship between endometrial cancer and lipid metabolism, which may aid in preventing cerebrovascular or cardiovascular diseases due to dyslipidemia and improving the quality of life in endometrial cancer survivors. PMID:23999769

  15. 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

  16. Mechanism of progestin resistance in endometrial precancer/cancer through Nrf2-survivin pathway

    PubMed Central

    Fan, Rujia; Wang, Yiying; Wang, Yue; Wei, Li; Zheng, Wenxin

    2017-01-01

    Progestin is commonly used for young patients suffering from endometrial hyperplasia or cancer. However, there is approximately 30% failure rate with unclear mechanism. We investigated if Nrf2-survivin pathway contributes the progestin resistance (PR) in this setting. Current study detected Nrf2 and survivin protein expression in post progestin treated endometrial tissue samples by using immunohistochemistry. Transfection of Nrf2 and survivin into endometrial cancer cells in vitro was done to determine the roles of Nrf2 and survivin in progestin resistance. Silence of survivin was then performed to explore if Nrf2-driven progestin resistance is mediated by survivin. Medorxyprogesterone acetate (MPA) and metformin were applied to examine the cellular proliferations under the controlled conditions. Overexpression of survivin and Nrf2 were found in progestin-resistant endometrial samples as well as in those areas with only partial responses after MPA treatment. In contrast, all responded endometrial tissue with complete decidualization showed negative expression of these two biomarkers. Exogenous overexpression of Nrf2 and survivin resulted in progestin resistance. In addition, reduction of survivin in endometrial cancer cells overcame the Nrf2 overexpression induced progestin resistance. Furthermore, Nrf2 and survivin expressions were effectively suppressed after withdrawal of MPA. Interestingly, metformin increased the progestin sensitivity by down regulation of Nrf2 and survivin. The findings suggest that dysregulation of Nrf2-survivin may represent part of the molecular mechanisms of progestin resistance in endometrial cancer. Detecting survivin and Nrf2 may predict progestin resistance, while targeting Nrf2 and survivin may represent a promising prevention and treatment strategy for endometrial cancer. PMID:28386373

  17. Chondroitin sulfate proteoglycan protein is stimulated by interleukin 11 and promotes endometrial epithelial cancer cell proliferation and migration.

    PubMed

    Winship, Amy; Van Sinderen, Michelle; Heffernan-Marks, Ariella; Dimitriadis, Eva

    2017-03-01

    Endometrial cancer is the most common gynecological cancer. We identified interleukin 11 (IL11) as a critical mediator of endometrial tumourigenesis and demonstrated that IL11 regulates chondroitin sulfate proteoglycan (CSPG4) in human placental trophoblasts. CSPG4 is a cell membrane protein overexpressed in numerous human cancers, although its role in endometrial cancer has not been investigated. We examined CSPG4 expression and localization in primary human type I endometrioid grade (G) 1-3 tumours by qPCR and immunohistochemistry and determined whether IL11 stimulated CSPG4. IL11 upregulated CSPG4 mRNA in HEC1A (G2-derived endometrial epithelial cancer cell line) cells. IL11 administration to BALB/c nude mice enhanced HEC1A xenograft tumour growth and increased CSPG4 protein in tumours. CSPG4 mRNA was unchanged between human G1-3 endometrial cancer and control tissues. CSPG4 protein levels were elevated in the epithelium of G2 and G3 endometrial cancer and in the tumour-associated stroma of G3 tumour tissues compared to proliferative phase or post-menopausal endometrium. CSPG4 knockdown by siRNA reduced HEC1A proliferation and migration in vitro and reduced gene expression of the key epithelial-to-mesenchymal transition (EMT) regulator SNAIL. Our data suggest that CSPG4 inhibition may impair endometrial cancer progression by reducing cancer cell proliferation, migration and potentially EMT.

  18. Follicle-stimulating hormone promotes age-related endometrial atrophy through cross-talk with transforming growth factor beta signal transduction pathway.

    PubMed

    Zhang, Dan; Li, Jingyi; Xu, Gufeng; Zhang, Runjv; Zhou, Chengliang; Qian, Yeqing; Liu, Yifeng; Chen, Luting; Zhu, Bo; Ye, Xiaoqun; Qu, Fan; Liu, Xinmei; Shi, Shuai; Yang, Weijun; Sheng, Jianzhong; Huang, Hefeng

    2015-04-01

    It is widely believed that endometrial atrophy in postmenopausal women is due to an age-related reduction in estrogen level. But the role of high circulating follicle-stimulating hormone (FSH) in postmenopausal syndrome is not clear. Here, we explored the role of high circulating FSH in physiological endometrial atrophy. We found that FSH exacerbated post-OVX endometrial atrophy in mice, and this effect was ameliorated by lowering FSH with Gonadotrophin-releasing hormone agonist (GnRHa). In vitro, FSH inhibited endometrial proliferation and promoted the apoptosis of primary cultured endometrial cells in a dose-dependent manner. In addition, upregulation of caspase3, caspase8, caspase9, autophagy-related proteins (ATG3, ATG5, ATG7, ATG12 and LC3) and downregulation of c-Jun were also observed in endometrial adenocytes. Furthermore, smad2 and smad3 showed a time-dependent activation in endometrial cells which can be partly inhibited by blocking the transforming growth factor beta receptor II (TβRII). In conclusion, FSH regulated endometrial atrophy by affecting the proliferation, autophagy and apoptosis of endometrial cells partly through activation of the transforming growth factor beta (TGFβ) pathway.

  19. 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…

  20. 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…

  1. Endometrial polyps in 2 African pygmy hedgehogs.

    PubMed

    Phillips, Irene D; Taylor, Jacqueline J; Allen, Andrew L

    2005-06-01

    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.

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

    ClinicalTrials.gov

    2017-01-31

    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

  3. [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.

  4. 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.

  5. "Do That Again": Evaluating Spoken Dialogue Interfaces

    NASA Technical Reports Server (NTRS)

    James, Frankie; Rayner, Manny; Hockey, Beth Ann

    2000-01-01

    We present a new technique for evaluating spoken dialogue interfaces that allows us to separate the dialogue behavior from the rest of the speech system. By using a dialogue simulator that we have developed, we can gather usability data on the system s dialogue interaction and behaviors that can guide improvements to the speech interface. Preliminary testing has shown promising results, suggesting that it is possible to test properties of dialogue separately from other factors such as recognition quality.

  6. Endometrial exosomes/microvesicles in the uterine microenvironment: a new paradigm for embryo-endometrial cross talk at implantation.

    PubMed

    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

  7. The utility of endometrial thickness measurement in asymptomatic postmenopausal women with endometrial fluid.

    PubMed

    Seckin, B; Ozgu-Erdinc, A S; Dogan, M; Turker, M; Cicek, M N

    2016-01-01

    The aim of this study was to assess the clinical usefulness of sonographic endometrium thickness measurement in asymptomatic postmenopausal women with endometrial fluid collection. Fifty-two asymptomatic postmenopausal women with endometrial fluid, who underwent endometrial sampling were evaluated. Histopathological findings revealed that 25 (48.1%) women had insufficient tissue, 20 (38.4%) had atrophic endometrium and 7 (13.5%) had endometrial polyps. No case of malignancy was found. There was no statistically significant difference between the various histopathological categories (insufficient tissue, atrophic endometrium and polyp) with regard to the mean single-layer endometrial thickness (1.54 ± 0.87, 2.04 ± 1.76 and 1.79 ± 0.69 mm, respectively, p = 0.436). Out of 44 patients with endometrial thickness of less than 3 mm, 38 (86.4%) had atrophic changes or insufficient tissue and 6 (13.6%) had endometrial polyps. In conclusion, if the endometrial thickness is 3 mm or less, endometrial sampling is not necessary in asymptomatic postmenopausal women with endometrial fluid.

  8. Locked nucleic acid-inhibitor of miR-205 decreases endometrial cancer cells proliferation in vitro and in vivo.

    PubMed

    Torres, Anna; Kozak, Joanna; Korolczuk, Agnieszka; Rycak, Dominika; Wdowiak, Paulina; Maciejewski, Ryszard; Torres, Kamil

    2016-11-08

    Pathogenesis of endometrial cancer has been connected with alterations of microRNA expression and in particular miR-205 up-regulation was consistently reported in this carcinoma. Presented study aimed to investigate if inhibition of miR-205 expression using LNA-modified-nucleotide would attenuate endometrial cancer cells proliferation in vitro and in vivo.In the course of the study we found that the proliferation of endometrial cancer cells (HEC-1-B, RL-95, KLE, Ishikawa) transfected with LNA-miR-205-inhibitor and evaluated using real time cell monitoring as well as standard cell proliferation assay, was significantly decreased. Next, LNA-miR-205-inhibitor was used to assess the in vivo effects of miR-205 inhibition of endometrial cancer growth. Cby.Cg-Foxn1/cmdb mice bearing endometrial cancer xenografts were intraperitoneally injected with nine dosages of 25mg/kg of miR-205-LNA-inhibitor or scramble control or phosphatase buffered saline and were observed for 32 days. We found that systemic administration of miR-205-LNA-inhibitor was technically possible, and exerted inhibitory effect on endometrial cancer xenograft growth in vivo with only mild toxic effects in treated animals.In conclusion our results suggest that systemic delivery of miR-205-LNA-inhibitor is feasible, devoid of significant toxicity, and could be a promising treatment strategy for endometrial cancer. Therefore it warrants further studies in other animal models.

  9. Locked nucleic acid-inhibitor of miR-205 decreases endometrial cancer cells proliferation in vitro and in vivo

    PubMed Central

    Torres, Anna; Kozak, Joanna; Korolczuk, Agnieszka; Rycak, Dominika; Wdowiak, Paulina; Maciejewski, Ryszard; Torres, Kamil

    2016-01-01

    Pathogenesis of endometrial cancer has been connected with alterations of microRNA expression and in particular miR-205 up–regulation was consistently reported in this carcinoma. Presented study aimed to investigate if inhibition of miR-205 expression using LNA-modified-nucleotide would attenuate endometrial cancer cells proliferation in vitro and in vivo. In the course of the study we found that the proliferation of endometrial cancer cells (HEC-1-B, RL-95, KLE, Ishikawa) transfected with LNA-miR-205-inhibitor and evaluated using real time cell monitoring as well as standard cell proliferation assay, was significantly decreased. Next, LNA-miR-205-inhibitor was used to assess the in vivo effects of miR-205 inhibition of endometrial cancer growth. Cby.Cg-Foxn1/cmdb mice bearing endometrial cancer xenografts were intraperitoneally injected with nine dosages of 25mg/kg of miR-205-LNA-inhibitor or scramble control or phosphatase buffered saline and were observed for 32 days. We found that systemic administration of miR-205-LNA-inhibitor was technically possible, and exerted inhibitory effect on endometrial cancer xenograft growth in vivo with only mild toxic effects in treated animals. In conclusion our results suggest that systemic delivery of miR-205-LNA-inhibitor is feasible, devoid of significant toxicity, and could be a promising treatment strategy for endometrial cancer. Therefore it warrants further studies in other animal models. PMID:27655663

  10. 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

  11. 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

  12. Prognostic and Clinical Significance of miRNA-205 in Endometrioid Endometrial Cancer.

    PubMed

    Wilczynski, Milosz; Danielska, Justyna; Dzieniecka, Monika; Szymanska, Bozena; Wojciechowski, Michal; Malinowski, Andrzej

    2016-01-01

    Endometrial cancer is one of the most common malignancies of the reproductive female tract, with endometrioid endometrial cancer being the most frequent type. Despite the relatively favourable prognosis in cases of endometrial cancer, there is a necessity to evaluate clinical and prognostic utility of new molecular markers. MiRNAs are small, non-coding RNA molecules that take part in RNA silencing and post-transcriptional regulation of gene expression. Altered expression of miRNAs may be associated with cancer initiation, progression and metastatic capabilities. MiRNA-205 seems to be one of the key regulators of gene expression in endometrial cancer. In this study, we investigated clinical and prognostic role of miRNA-205 in endometrioid endometrial cancer. After total RNA extraction from 100 archival formalin-fixed paraffin-embedded tissues, real-time quantitative RT-PCR was used to define miRNA-205 expression levels. The aim of the study was to evaluate miRNA-205 expression levels in regard to patients' clinical and histopathological features, such as: survival rate, recurrence rate, staging, myometrial invasion, grading and lymph nodes involvement. Higher levels of miRNA-205 expression were observed in tumours with less than half of myometrial invasion and non-advanced cancers. Kaplan-Maier analysis revealed that higher levels of miRNA-205 were associated with better overall survival (p = 0,034). These results indicate potential clinical utility of miRNA-205 as a prognostic marker.

  13. Prognostic and Clinical Significance of miRNA-205 in Endometrioid Endometrial Cancer

    PubMed Central

    Wilczynski, Milosz; Wojciechowski, Michal; Malinowski, Andrzej

    2016-01-01

    Endometrial cancer is one of the most common malignancies of the reproductive female tract, with endometrioid endometrial cancer being the most frequent type. Despite the relatively favourable prognosis in cases of endometrial cancer, there is a necessity to evaluate clinical and prognostic utility of new molecular markers. MiRNAs are small, non-coding RNA molecules that take part in RNA silencing and post-transcriptional regulation of gene expression. Altered expression of miRNAs may be associated with cancer initiation, progression and metastatic capabilities. MiRNA-205 seems to be one of the key regulators of gene expression in endometrial cancer. In this study, we investigated clinical and prognostic role of miRNA-205 in endometrioid endometrial cancer. After total RNA extraction from 100 archival formalin-fixed paraffin-embedded tissues, real-time quantitative RT-PCR was used to define miRNA-205 expression levels. The aim of the study was to evaluate miRNA-205 expression levels in regard to patients’ clinical and histopathological features, such as: survival rate, recurrence rate, staging, myometrial invasion, grading and lymph nodes involvement. Higher levels of miRNA-205 expression were observed in tumours with less than half of myometrial invasion and non-advanced cancers. Kaplan-Maier analysis revealed that higher levels of miRNA-205 were associated with better overall survival (p = 0,034). These results indicate potential clinical utility of miRNA-205 as a prognostic marker. PMID:27737015

  14. Isoliquiritigenin induces apoptosis and autophagy and inhibits endometrial cancer growth in mice

    PubMed Central

    Shieh, Tzong-Ming; Huang, Tsui-Chin; Lin, Li-Chun; Wang, Kai-Lee; Hsia, Shih-Min

    2016-01-01

    Endometrial cancer is the most common cancer in women, typically with onset after menopause. Isoliquiritigenin (ISL), a licorice flavonoid, was previously shown to have anti-oxidant, anti-inflammatory, and tumor suppression effects. In this study, we investigated the anti-tumor effect of ISL on human endometrial cancer both in vitro and in vivo. We used telomerase-immortalized human endometrial stromal cells (T-HESCs) and human endometrial cancer cell lines (Ishikawa, HEC-1A, and RL95-2 cells) as targets. The effects of ISL on cell proliferation, cell cycle regulation, and apoptosis or autophagy-related protein expression were examined. In addition, we conducted in vivo experiments to confirm the inhibitory effects of ISL on cancer cells. ISL significantly inhibited the viability of cancer cells in a dose- and time-dependent manner but with little toxicity on normal cells. In addition, flow cytometry analysis indicated that ISL induced sub-G1 or G2/M phase arrest. ISL treatment activated the extracellular signal regulated kinase signaling pathway to enhance the protein expression of caspase-7/LC3BII associated with apoptosis/autophagy. Furthermore, ISL suppressed xenograft tumor growth in vivo. Taken together, these findings suggest that ISL may induce apoptosis, autophagy, and cell growth inhibition, indicating its potential as a therapeutic agent for human endometrial cancer. PMID:27708238

  15. RXRα is Upregulated in First Trimester Endometrial Glands of Spontaneous Abortions Unlike LXR and PPARγ

    PubMed Central

    Knabl, J.; Vattai, A.; Hüttenbrenner, R.; Hutter, S.; Karsten, M.

    2016-01-01

    Nuclear receptors are necessary for uterine invasion of the trophoblast and therefore important for maintaining a viable pregnancy. The aim of this study was to investigate the expression pattern and frequency of LXR, PPARγ and RXRα under physiological circumstances and in spontaneous abortions in endometrial glands and decidual tissue cells. A total of 28 (14 physiologic pregnancies/14 spontaneous abortion) human pregnancies in first trimester were analyzed for expression of the nuclear receptors LXR, RXRα and PPARγ. Expression changes were evaluated by immunohistochemistry in decidual tissue and endometrial glands of the decidua. RXRα expression was up-regulated in the endometrial glands of spontaneous abortion (P<0.015). Similar up regulation of RXRα was found in decidual tissue (P<0.05). LXR and PPARγ expression was unchanged in spontaneous abortion. By Correlation analysis we found a trend to positive correlation of LXR and PPARγ (Spearman correlation coefficient r=0.56, P=0.07) in endometrial glands. In decidual tissue, we found significant negative correlation in the control group, for the combination of RXRα and PPARγ (Spearman correlation coefficient r=0.913, P=0.03). Our data show that RXRα expression is increased in miscarriage in endometrial glands and correlation analysis showed that negative correlation between RXRα and PPARγ disappears in miscarriage. This shift is supposable responsible for the loss of regular function in trophoblast and embryonic tissue. PMID:28076928

  16. Reduced connexin 43 in eutopic endometrium and cultured endometrial stromal cells from subjects with endometriosis.

    PubMed

    Yu, Jie; Boicea, Anisoara; Barrett, Kara L; James, Christopher O; Bagchi, Indrani C; Bagchi, Milan K; Nezhat, Ceana; Sidell, Neil; Taylor, Robert N

    2014-03-01

    Accumulating evidence indicates that reduced fecundity associated with endometriosis reflects a failure of embryonic receptivity. Microdomains composed of endometrial gap junctions, which facilitate cell-cell communication, may be implicated. Pharmacological or genetic inhibition of connexin (Cx) 43 block human endometrial cell differentiation in vitro and conditional uterine deletion of Cx43 alleles cause implantation failure in mice. The aim of this study was to determine whether women with endometriosis have reduced eutopic endometrial Cx43. Cx26 acted as a control. Endometrial biopsies were collected from age, race and cycle phase-matched women without (15 controls) or with histologically confirmed endometriosis (15 cases). Immunohistochemistry confirmed a predominant localization of Cx43 in the endometrial stroma, whereas Cx26 was confined to the epithelium. Cx43 immunostaining was reduced in eutopic biopsies of endometriosis subjects and western blotting of tissue lysates confirmed lower Cx43 levels in endometriosis cases, with Cx43/β-actin ratios=.4±1.5 in control and =1.2±0.3 in endometriosis biopsies (P<0.01). When endometrial stromal cells (ESC) were isolated from endometriosis cases, Cx43 levels and scrape loading-dye transfer were reduced by ∼45% compared with ESC from controls. In vitro decidualization of ESC derived from endometriosis versus control subjects resulted in lesser epithelioid transformation and a significantly reduced up-regulation of Cx43 protein (1.2±0.2- versus 1.7±0.4-fold, P<0.01). No changes in Cx26 were observed. While basal steady-state levels of Cx43 mRNA did not differ with respect to controls, ESC from endometriosis cases failed to manifest a response to hormone treatment in vitro. In summary, eutopic endometrial Cx43 concentrations in endometriosis cases were <50% those of controls in vivo and in vitro, functional gap junctions were reduced and hormone-induced Cx43 mRNA levels were blunted.

  17. 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

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

    ClinicalTrials.gov

    2017-03-20

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

  19. An early-screening biomarker of endometrial carcinoma: NGAL is associated with epithelio-mesenchymal transition

    PubMed Central

    Li, Ting; Yu, Li; Wen, Jia

    2016-01-01

    neutrophilgelatinase-associated lipocalin is currently one of the most interesting and enigmatic proteins involved in the development of malignancies. In this study, we found that the expression of neutrophilgelatinase-associated lipocalin was up-regulated in endometrial cancer tissues and cell lines, significantly increased in early-grade ones, suggesting it may serve as a biomarker for early-stage screening for endometrial carcinoma. Moreover, neutrophilgelatinase-associated lipocalin was up-regulated in Ishikawa cells under going epithelio-mesenchymal transition induced by epidermal growth factor (5 ng/ml). Up-regulation of neutrophilgelatinase-associated lipocalin may correlate with the down-regulation of E-cadherin expression, up-regulation of Vimentin expression, enhanced cell migration, invasion and proliferation, which are the typical hallmarks of epithelio-mesenchymal transition processes. neutrophilgelatinase-associated lipocalin may play a dual role during tumorigenetic and developmental processes of endometrial carcinoma. These results suggested neutrophilgelatinase-associated lipocalin to be a potential molecular target in the early diagnosis and treatment of endometrial carcinoma. Further studies are warranted to clarify the molecular mechanisms behind the expression and function of neutrophilgelatinase-associated lipocalin and epithelio-mesenchymal transition. PMID:27863382

  20. Isolated Abdominal Wall Metastasis of Endometrial Carcinoma

    PubMed Central

    Simões, Jorge; Gonçalves, Matilde; Matos, Isabel

    2014-01-01

    A woman in her mid-60s presented with a bulky mass on the anterior abdominal wall. She had a previous incidental diagnosis of endometrial adenocarcinoma FIGO stage IB following a vaginal hysterectomy. Physical exam and imaging revealed a well circumscribed bulging tumour at the umbilical region, measuring 10 × 9 × 9 cm, with overlying intact skin and subcutaneous tissue. Surgical resection was undertaken, and histological examination showed features of endometrial carcinoma. She began chemotherapy and is alive with no signs of recurrent disease one year after surgery. This case brings up to light an atypical location of a solitary metastasis of endometrial carcinoma. PMID:25349753

  1. Perfluorooctanoic acid induces human Ishikawa endometrial cancer cell migration and invasion through activation of ERK/mTOR signaling

    PubMed Central

    Li, Fujun; Wang, Yixong; Xu, Yang; Zhang, Mei; Zhang, Xiaoqian; Ying, Xiaoyan; Zhang, Xuesen

    2016-01-01

    Perfluorooctanoic acid (PFOA) is a common environmental pollutant that has been associated with various diseases, including cancer. We explored the molecular mechanisms underlying PFOA-induced endometrial cancer cell invasion and migration. PFOA treatment enhanced migration and invasion by human Ishikawa endometrial cancer cells, which correlated with decreased E-cadherin expression, a marker of epithelial-mesenchymal transition. PFOA also induced activation of ERK1/2/mTOR signaling. Treatment with rapamycin, an mTOR inhibitor, antagonized the effects of PFOA and reversed the effects of PFOA activation in a xenograft mouse model of endometrial cancer. Consistent with these results, pre-treatment with rapamycin abolished PFOA-induced down-regulation of E-cadherin expression. These results indicate that PFOA is a carcinogen that promotes endometrial cancer cell migration and invasion through activation of ERK/mTOR signaling. PMID:27589685

  2. Limits of Simple Dialogue Acts for Tactical Questioning Dialogues

    DTIC Science & Technology

    2011-07-01

    1 gives some facts about the incident. For example, Amani knows that the name of the suspected sniper is Saif , and that he lives 2 Object Attribute...Value T/F strange-man name saif true strange-man name unknown false strange-man location store true brother name mohammed true Table 1: Some facts...name, saif de- fines a character dialogue act with a meaning equivalent to “the suspect is named Saif ” (assert), and two user dialogue acts, equivalent

  3. GPR54 is a target for suppression of metastasis in endometrial cancer.

    PubMed

    Kang, Hyun Sook; Baba, Tsukasa; Mandai, Masaki; Matsumura, Noriomi; Hamanishi, Junzo; Kharma, Budiman; Kondoh, Eiji; Yoshioka, Yumiko; Oishi, Shinya; Fujii, Nobutaka; Murphy, Susan K; Konishi, Ikuo

    2011-04-01

    Invasion into deep myometrium and/or lymphovascular space is a well-known risk factor for endometrial cancer metastasis, resulting in poor prognosis. It is therefore clinically important to identify novel molecules that suppress tumor invasion. Reduced expression of the metastasis suppressor, kisspeptin (KISS1), and its endogenous receptor, GPR54, has been reported in several cancers, but the significance of the KISS1/GPR54 axis in endometrial cancer metastasis has not been clarified. Metastin-10 is the minimal bioactive sequence of genetic products of KISS1. Clinicopathological analysis of 92 endometrial cancers revealed overall survival is improved in cancers with high expression of GPR54 (P < 0.05) and that GPR54 expression is associated with known prognostic factors including FIGO stage, grade, and deep myometrial invasion. Through RNAi and microarray analyses, metastin-10 was predicted to suppress metastasis of GPR54-expressing endometrial cancers in vivo. Methylation analysis revealed GPR54 is epigenetically regulated. Metastin-GPR54 axis function was restored following treatment with the DNA hypomethylating agent 5-aza-DC. These data suggest that metastin-10 may be effective at inhibiting the metastatic spread of endometrial cancers in combination with demethylating agents to induce GPR54 expression.

  4. Expression of epigenetic effectors in decidualizing human endometrial stromal cells.

    PubMed

    Grimaldi, Giulia; Christian, Mark; Quenby, Siobhan; Brosens, Jan J

    2012-09-01

    Cyclic differentiation of human endometrial stromal cells (HESCs) into decidual cells is a highly coordinated process essential for embryo implantation and pregnancy. This differentiation process is closely recapitulated in culture upon exposure of purified HESCs to cyclic AMP and progesterone signaling. Mining of gene expression data revealed that HESCs express 147 genes coding for epigenetic effectors, 33 (22%) of which are significantly regulated (P < 0.05) upon decidualization. Among these are genes encoding for histone-modifying proteins and their cofactors, histone-binding proteins, histone variants, CpG-binding proteins and DNA methyltransferases (DNMTs). Interestingly, more than two-thirds of differentially expressed chromatin-modifying genes are down-regulated upon the transition from a proliferative to a differentiated HESC phenotype. Despite the strong regulation of DNMTs, colorimetric and long interspersed nuclear element 1 methylation assays did not show global changes in DNA methylation levels upon differentiation of HESCs. Taken together, the coordinated regulation of diverse effector molecules suggests that complex epigenetic modification at specific loci underpins the acquisition of a decidual endometrial phenotype.

  5. 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

  6. 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.

  7. Intraperitoneal Paclitaxel, Doxorubicin Hydrochloride, and Cisplatin in Treating Patients With Stage III-IV Endometrial Cancer

    ClinicalTrials.gov

    2016-10-26

    Endometrial Adenosquamous Carcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Mixed Adenocarcinoma; Endometrial Serous Adenocarcinoma; Endometrial Squamous Cell Carcinoma; Endometrial Undifferentiated Carcinoma; Recurrent Uterine Corpus Carcinoma; Stage IIIA Uterine Corpus Cancer; Stage IIIC Uterine Corpus Cancer; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer

  8. 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

  9. 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

  10. Treatment Options by Stage (Endometrial Cancer)

    MedlinePlus

    ... Stage II endometrial cancer. Cancer has spread into connective tissue of the cervix, but has not spread outside ... uterus. In stage II , cancer has spread into connective tissue of the cervix , but has not spread outside ...

  11. [Radiotherapy of cervix and endometrial carcinoma].

    PubMed

    Barillot, I; Haie-Méder, C; Charra Brunaud, C; Peignaux, K; Kerr, C; Thomas, L

    2016-09-01

    External irradiation and brachytherapy still have a major place in the treatment of cervix and endometrial carcinoma. This review presents the French guidelines in terms of preparation and choice of irradiation techniques of these gynecological malignancies.

  12. Indications and options for endometrial ablation.

    PubMed

    2008-11-01

    Endometrial ablation is an effective therapeutic option for the management of menorrhagia in properly selected patients. Hysteroscopic and non-hysteroscopic techniques offer similar rates of symptom relief and patient satisfaction.

  13. Molecular Biology and Prevention of Endometrial Cancer

    DTIC Science & Technology

    2006-07-01

    and analyzed, which would most likely take an additional 3-6 months after enrollment. Aim 2: To analyze vaginal and cervical adenocarcinomas...Endometrial Cancer PRINCIPAL INVESTIGATOR: LTC George Larry Maxwell, M.D. CONTRACTING ORGANIZATION: Henry M. Jackson Foundation for...Annual 3. DATES COVERED 117 Jun 2005 – 16 Jun 2006 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Molecular Biology and Prevention of Endometrial Cancer

  14. Revised FIGO staging system for endometrial cancer.

    PubMed

    Lewin, Sharyn N

    2011-06-01

    In 1988 the International Federation of Gynecologists and Obstetricians (FIGO) developed a surgical staging system for endometrial cancer. The FIGO staging system was recently revised in 2009 to reflect our growing understanding of the natural history of endometrial cancer. In this review, we describe the revised 2009 FIGO staging system for tumors of the uterine corpus and examine the effect of the new changes in the staging criteria.

  15. 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

  16. Using a Dialogue System Based on Dialogue Maps for Computer Assisted Second Language Learning

    ERIC Educational Resources Information Center

    Choi, Sung-Kwon; Kwon, Oh-Woog; Kim, Young-Kil; Lee, Yunkeun

    2016-01-01

    In order to use dialogue systems for computer assisted second-language learning systems, one of the difficult issues in such systems is how to construct large-scale dialogue knowledge that matches the dialogue modelling of a dialogue system. This paper describes how we have accomplished the short-term construction of large-scale and…

  17. Feedback Dialogues That Stimulate Students' Reflective Thinking

    ERIC Educational Resources Information Center

    Van der Schaaf, Marieke; Baartman, Liesbeth; Prins, Frans; Oosterbaan, Anne; Schaap, Harmen

    2013-01-01

    How can feedback dialogues stimulate students' reflective thinking? This study aims to investigate: (1) the effects of feedback dialogues between teachers and students on students' perceptions of teacher feedback and (2) the relation between features of feedback dialogues and students' thinking activities as part of reflective thinking. A…

  18. 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…

  19. 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…

  20. 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…

  1. 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…

  2. 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

  3. 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.

  4. 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

  5. Expression of GLUT1 and GLUT3 glucose transporters in endometrial and breast cancers.

    PubMed

    Krzeslak, Anna; Wojcik-Krowiranda, Katarzyna; Forma, Ewa; Jozwiak, Paweł; Romanowicz, Hanna; Bienkiewicz, Andrzej; Brys, Magdalena

    2012-07-01

    Cancer cells have accelerated metabolism and high glucose requirements. The up-regulation of specific glucose transporters may represent a key mechanism by which malignant cells may achieve increased glucose uptake to support the high rate of glycolysis. In present study we analyzed the mRNA and protein expression of GLUT1 and GLUT3 glucose transporters by quantitative real-time polymerase chain reaction (Q-PCR) and Western blotting technique in 76 cases of endometrial carcinoma and 70 cases of breast carcinoma. SLC2A1 and SLCA2A3 mRNAs expression was found, respectively in 100% and 97.4% samples of endometrial cancers and only in 50% and 40% samples of breast cancers. In endometrial cancers GLUT1 and GLUT3 protein expression was identified in 67.1% and 30.3% of cases. Analogously, in breast cancers in 48.7% and 21% of samples, respectively. The results showed that both endometrial and breast poorly differentiated tumors (grade 2 and 3) had significantly higher GLUT1 and GLUT3 expression than well-differentiated tumors (grade 1). Statistically significant association was found between SLCA2A3 mRNA expression and estrogen and progesterone receptors status in breast cancers. GLUT1 has been reported to be involved in the uptake of glucose by endometrial and breast carcinoma cells earlier and the present study determined that GLUT3 expression is also involved. GLUT1 and GLUT3 seem to be important markers in endometrial and breast tumors differentiation.

  6. Differential gene expression in endometrium, endometrial lymphocytes, and trophoblasts during successful and abortive embryo implantation.

    PubMed

    Tayade, Chandrakant; Black, Gordon P; Fang, Yuan; Croy, B Anne

    2006-01-01

    Prenatal mortality reaching 30% occurs during the first weeks of gestation in commercial swine. Mechanisms for this are unknown although poor uterine blood supply has been postulated. In other species, vascular endothelial growth factor, hypoxia-inducible factor 1-alpha, and IFN-gamma regulate gestational endometrial angiogenesis. Vascular endothelial growth factor and hypoxia-inducible factor 1-alpha are also important for placental angiogenesis while trophoblastic expression of Fas ligand is thought to protect conceptuses against immune-mediated pregnancy loss. In this study, we document dynamic, peri-implantation differences in transcription of genes for angiogenesis, cytokine production, and apoptosis regulation in the endometrium, and laser capture microdissected endometrial lymphocytes and trophoblasts associated with healthy or viable but arresting porcine fetuses. In healthy implantation sites, endometrial gene expression levels differed between anatomic subregions and endometrial lymphocytes showed much greater transcription of angiogenic genes than trophoblasts. In arresting fetal sites, uterine lymphocytes had no angiogenic gene transcription and showed rapid elevation in transcription of proinflammatory cytokines Fas and Fas ligand while trophoblasts showed elevated transcription of IFN-gamma and Fas. This model of experimentally accessible spontaneous fetal loss, involving blocked maternal angiogenesis, should prove valuable for further investigations of peri-implantation failure of normally conceived and surgically transferred embryos in many species, including the human.

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

    PubMed

    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.

  8. Dialysis therapies: a National Dialogue.

    PubMed

    Mehrotra, Rajnish; Agarwal, Anil; Bargman, Joanne M; Himmelfarb, Jonathan; Johansen, Kirsten L; Watnick, Suzanne; Work, Jack; McBryde, Kevin; Flessner, Michael; Kimmel, Paul L

    2014-04-01

    The National Institute of Diabetes, Digestive, and Kidney Diseases-supported Kidney Research National Dialogue asked the scientific community to formulate and prioritize research objectives that would improve our understanding of kidney function and disease. Kidney Research National Dialogue participants identified the need to improve outcomes in ESRD by decreasing mortality and morbidity and enhancing quality of life as high priority areas in kidney research. To reach these goals, we must identify retained toxins in kidney disease, accelerate technologic advances in dialysate composition and devices to remove these toxins, advance vascular access, and identify measures that decrease the burden of disease in maintenance dialysis patients. Together, these research objectives provide a path forward for improving patient-centered outcomes in ESRD.

  9. Figure analysis: An implementation dialogue.

    PubMed

    Wiles, Amy M

    2016-07-08

    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.

  10. Workplace aggression: beginning a dialogue.

    PubMed

    McLemore, Monica R

    2006-08-01

    The June 2005 Clinical Journal of Oncology Nursing editorial titled "Communication: Whose Problem Is It?" (Griffin-Sobel, 2005) was written to begin a dialogue about a phenomenon frequently experienced yet rarely discussed: workplace aggression, also known as disruptive behavior. Prompted by a groundbreaking study published in the American Journal of Nursing by Rosenstein and O'Daniel (2005), the editorial challenged oncology nurses to begin to fix problems of communication. After reflecting on both of the articles and considering my own experience as a nurse manager, clinician, and scholar, I decided to explore the topic as it relates to nurse-to-nurse workplace aggression. The following is a summary of interviews with nurse managers, nurse practitioners, and nurse scientists about root causes and effective strategies to manage these sometimes complicated situations. This article is meant to continue the dialogue about the very sensitive issue. Confidentiality has been maintained, and I welcome your comments.

  11. Endometrial stem cells in regenerative medicine.

    PubMed

    Verdi, Javad; Tan, Aaron; Shoae-Hassani, Alireza; Seifalian, Alexander M

    2014-01-01

    First described in 2004, endometrial stem cells (EnSCs) are adult stem cells isolated from the endometrial tissue. EnSCs comprise of a population of epithelial stem cells, mesenchymal stem cells, and side population stem cells. When secreted in the menstrual blood, they are termed menstrual stem cells or endometrial regenerative cells. Mounting evidence suggests that EnSCs can be utilized in regenerative medicine. EnSCs can be used as immuno-modulatory agents to attenuate inflammation, are implicated in angiogenesis and vascularization during tissue regeneration, and can also be reprogrammed into induced pluripotent stem cells. Furthermore, EnSCs can be used in tissue engineering applications and there are several clinical trials currently in place to ascertain the therapeutic potential of EnSCs. This review highlights the progress made in EnSC research, describing their mesodermal, ectodermal, and endodermal potentials both in vitro and in vivo.

  12. Rapidly Customizable Spoken Dialogue Systems

    DTIC Science & Technology

    2009-01-28

    Human-Centered Computing , Language Models, Domain-independent grammar 16. SECURITY CLASSIFICATION OF: a. REPORT U b. ABSTRACT u c. THIS PAGE u...many applications, including dialogue-based human- computer interfaces to intelligent systems/agents, tutoring and advice-giving systems, systems...variety of ex- ternal resources. We built a subsystem for unknown word lookup that accesses lexical resources such as Wordnet (Miller, 1995) and Comlex

  13. Spoken Dialogue Interfaces: Integrating Usability

    NASA Astrophysics Data System (ADS)

    Spiliotopoulos, Dimitris; Stavropoulou, Pepi; Kouroupetroglou, Georgios

    Usability is a fundamental requirement for natural language interfaces. Usability evaluation reflects the impact of the interface and the acceptance from the users. This work examines the potential of usability evaluation in terms of issues and methodologies for spoken dialogue interfaces along with the appropriate designer-needs analysis. It unfolds the perspective to the usability integration in the spoken language interface design lifecycle and provides a framework description for creating and testing usable content and applications for conversational interfaces. Main concerns include the problem identification of design issues for usability design and evaluation, the use of customer experience for the design of voice interfaces and dialogue, and the problems that arise from real-life deployment. Moreover it presents a real-life paradigm of a hands-on approach for applying usability methodologies in a spoken dialogue application environment to compare against a DTMF approach. Finally, the scope and interpretation of results from both the designer and the user standpoint of usability evaluation are discussed.

  14. 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

  15. MicroRNA-134 suppresses endometrial cancer stem cells by targeting POGLUT1 and Notch pathway proteins.

    PubMed

    Gao, Yongtao; Liu, Te; Huang, Yongyi

    2015-01-16

    We aimed to ascertain the role of microRNAs (miRNAs) in regulating human endometrial cancer stem cells (HuECSCs). The expression level of miRNA-134 (miR-134), a member of the DLK1-DIO3 genomic imprinted miRNA cluster, differed significantly between HuECSCs and human endometrial cancer cells (HuECCs). miR-134 inhibited HuECSCs proliferation and migration by targeting protein O-glucosyltransferase 1 (POGLUT1) expression. Exogenous miR-134 overexpression downregulated POGLUT1 and Notch pathway proteins in HuECSCs in vitro. miR-134 overexpression affected the G2/M phase of HuECSCs and suppressed the growth of xenograft tumours formed. Thus, endogenous miR-134 regulation in HuECSCs may suppress tumourigenesis in human endometrial carcinoma.

  16. STAT1 drives tumor progression in serous papillary endometrial cancer.

    PubMed

    Kharma, Budiman; Baba, Tsukasa; Matsumura, Noriomi; Kang, Hyun Sook; Hamanishi, Junzo; Murakami, Ryusuke; McConechy, Melissa M; Leung, Samuel; Yamaguchi, Ken; Hosoe, Yuko; Yoshioka, Yumiko; Murphy, Susan K; Mandai, Masaki; Hunstman, David G; Konishi, Ikuo

    2014-11-15

    Recent studies of the interferon-induced transcription factor STAT1 have associated its dysregulation with poor prognosis in some cancers, but its mechanistic contributions are not well defined. In this study, we report that the STAT1 pathway is constitutively upregulated in type II endometrial cancers. STAT1 pathway alteration was especially prominent in serous papillary endometrial cancers (SPEC) that are refractive to therapy. Our results defined a "SPEC signature" as a molecular definition of its malignant features and poor prognosis. Specifically, we found that STAT1 regulated MYC as well as ICAM1, PD-L1, and SMAD7, as well as the capacity for proliferation, adhesion, migration, invasion, and in vivo tumorigenecity in cells with a high SPEC signature. Together, our results define STAT1 as a driver oncogene in SPEC that modulates disease progression. We propose that STAT1 functions as a prosurvival gene in SPEC, in a manner important to tumor progression, and that STAT1 may be a novel target for molecular therapy in this disease.

  17. 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.

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

    PubMed Central

    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 MJ; Ashton, Katie; Otton, Geoffrey; Proietto, Tony; Liu, Tao; Mints, Miriam; Tham, Emma; Consortium, CHIBCHA; Jun Li, Mulin; 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

    2016-01-01

    We conducted a meta-analysis of three endometrial cancer GWAS and two replication phases totaling 7,737 endometrial cancer cases and 37,144 controls of European ancestry. Genome-wide imputation and meta-analysis identified five novel 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). A second independent 8q24.21 signal (rs17232730) was found. Functional studies of the 13q22.1 locus showed that rs9600103 (pairwise r2=0.98 with rs11841589) is located in a region of active chromatin that interacts with the KLF5 promoter region. The rs9600103-T endometrial cancer protective allele suppressed gene expression in vitro suggesting that regulation of KLF5 expression, 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. Tumor progression, metastasis, and modulators of epithelial-mesenchymal transition in endometrioid endometrial carcinoma: an update.

    PubMed

    Makker, Annu; Goel, Madhu Mati

    2016-02-01

    Endometrioid endometrial carcinoma (EEC), also known as type 1 endometrial cancer (EC), accounts for over 70-80% of all cases that are usually associated with estrogen stimulation and often develops in a background of atypical endometrial hyperplasia. The increased incidence of EC is mainly confined to this type of cancer. Most EEC patients present at an early stage and generally have a favorable prognosis; however, up to 30% of EEC present as high risk tumors, which have invaded deep into the myometrium at diagnosis and progressively lead to local or extra pelvic metastasis. The poor survival of advanced EC is related to the lack of effective therapies, which can be attributed to poor understanding of the molecular mechanisms underlying the progression of disease toward invasion and metastasis. Multiple lines of evidence illustrate that epithelial-mesenchymal transition (EMT)-like events are central to tumor progression and malignant transformation, endowing the incipient cancer cell with invasive and metastatic properties. The aim of this review is to summarize the current knowledge on molecular events associated with EMT in progression, invasion, and metastasis of EEC. Further, the role of epigenetic modifications and microRNA regulation, tumor microenvironment, and microcystic elongated and fragmented glands like invasion pattern have been discussed. We believe this article may perhaps stimulate further research in this field that may aid in identifying high risk patients within this clinically challenging patient group and also lead to the recognition of novel targets for the prevention of metastasis - the most fatal consequence of endometrial carcinogenesis.

  20. Effects of DEHP on endometrial receptivity and embryo implantation in pregnant mice.

    PubMed

    Li, Rui; Yu, Chao; Gao, Rufei; Liu, Xueqing; Lu, Jing; Zhao, Letian; Chen, Xuemei; Ding, Yubin; Wang, Yingxiong; He, Junlin

    2012-11-30

    Di-(2-ethylhexyl)-phthalate (DEHP) is a ubiquitous environmental pollutant and endocrine disruptor (ED) that causes serious adverse effects on animal and human health. The harmful effects of DEHP on human reproduction are increasingly recognized, especially in women. However, it is not known how endometrial receptivity and embryo implantation, which play important roles in the establishment of pregnancy, are affected by DEHP. This study was aimed towards investigating the effects of DEHP on endometrial receptivity and embryo implantation in pregnant mice. The pregnant mice received DEHP at 0, 250, 500 and 1000 mg/kg/day from day 1 (D1) of gestation until sacrifice. Administration of DEHP led to compromised endometrial receptivity and decreased number of implantation sites. The mRNA and protein expression levels of ERα, PR and E-cadherin, but not those of HoxA10 and MMP-2, were up-regulated by DEHP in the mouse endometrium. The results further suggested that DEHP disrupts the MAPK and NF-κB signaling pathways. This was maybe one of paths which influenced the E-cadherin expression. In conclusion, DEHP reduced endometrial receptivity and impaired embryo implantation by influencing the expression of hormone receptors and E-cadherin. Therefore, determining the full extent of the hazards of DEHP to human reproduction will be vital to developing and implementing effective protective measures.

  1. 21 CFR 884.1060 - Endometrial aspirator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... and pipette, or catheter. This device is used to study endometrial cytology (cells). (b) Classification. Class II. The special controls for this device are: (1) FDA's: (i) “Use of International Standard...) Sterility Review Guidance of 2/12/90 (K90-1),” (2) Labeling: (i) Indication: Only to evaluate...

  2. 21 CFR 884.1185 - Endometrial washer.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... with negative pressure. This device is used to study endometrial cytology (cells). (b) Classification. Class II. The special controls for this device are: (1) FDA's: (i) “Use of International Organization... Testing,’ ” and (ii) “510(k) Sterility Review Guidance of 2/12/90 (K90-1),” (2) Labeling: (i)...

  3. Molecular Biology and Prevention of Endometrial Cancer

    DTIC Science & Technology

    2009-07-01

    of the oral contraceptive pill (OCP). Project 1: Objectives completed and data previously submitted with 2004 report. Data published this past year...molecular aberrations associated with endometrial carcinogenesis and the biologic mechanisms underlying the protective effect of oral contraceptive (OC...not been altered appreciably. Despite the known protective effect of oral contraceptives , little has been learned regarding the underlying mechanism

  4. Endometrial polyp surveillance in premenopausal breast cancer patients using tamoxifen

    PubMed Central

    Jeon, Se Jeong; Lee, Jae Il; Kim, Hee Seung; Kim, Jae Weon; Park, Noh Hyun; Song, Yong Sang

    2017-01-01

    Objective To describe the endometrial pathologic lesions in premenopausal breast cancer patients with a history of tamoxifen (TMX) use. Methods We retrospectively reviewed the medical records of 120 premenopausal breast cancer patients with a history of TMX use that had undergone a gynecological examination. Results Among 120 patients, 44.2% (n=53) were asymptomatic with an endometrial thickness ≥5 mm, as assessed by transvaginal ultrasonography. Of the patients that reported abnormal uterine bleeding, 5% (n=6) had an endometrial thickness <5 mm and 20% (n=24) had an endometrial thickness ≥5 mm by transvaginal ultrasonography. The final group of patients were asymptomatic, but showed an abnormal endometrial lesion, such as an endometrial polyp, by transvaginal ultrasonography (30.8%, n=37). Of the 56 benign lesions that were histologically reviewed, 50 (41.7%) were endometrial polyps, 3 (2.5%) were submucosal myomas, 2 (1.7%) were endometrial hyperplasias, and 1 (0.8%) was chronic endometritis. There were 64 (53.3%) other non-pathologic conditions, including secreting, proliferative, and atrophic endometrium, or in some cases, there was insufficient material for diagnosis. In our data, only one case was reported as a complex hyperplasia without atypia arising from an endometrial polyp, and one patient was diagnosed with endometrioid adenocarcinoma. Conclusion For premenopausal breast cancer patients with a history of TMX use, the majority of the patients were asymptomatic, and endometrial polyps were the most common endometrial pathology observed. Therefore, we believe that endometrial assessment before starting TMX treatment, and regular endometrial screening throughout TMX treatment, are reasonable suggestions for premenopausal breast cancer patients. PMID:28217668

  5. 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

  6. Does IGF-1 play a role in the biology of endometrial cancer?

    PubMed

    Majchrzak-Baczmańska, Dominika; Malinowski, Andrzej

    2016-01-01

    Insulin-like growth factor 1 (IGF-1) is a mitogen which plays a key role in regulating cell proliferation, differentiation, and apoptosis. It belongs to the family of proteins also composed of insulin-like growth factor 2 (IGF-2), two types of membrane receptors (IGF-1R and IGF-2R), 6 binding proteins (IGFBP 1-6), hydrolyzing proteases, and reactive molecules binding proteins, which regulate the activity of growth factors. Disturbances in the functioning of IGFBP/IGF/1GF1R can lead to induction of carcinogenesis, which has been demonstrated in breast, prostate or colon cancers. Findings evaluating the role of IGF-1 in endometrial cancer biology are ambiguous and contradictory. Therefore, in the present study, we analyzed the role of IGF-1 in the process of carcinogenesis of endometrial cancer, based on the available literature.

  7. Mesenchymal Stem/Progenitors and Other Endometrial Cell Types From Women With Polycystic Ovary Syndrome (PCOS) Display Inflammatory and Oncogenic Potential

    PubMed Central

    Piltonen, T. T.; Chen, J.; Erikson, D. W.; Spitzer, T. L. B.; Barragan, F.; Rabban, J. T.; Huddleston, H.; Irwin, J. C.

    2013-01-01

    Context: Endometrium in polycystic ovary syndrome (PCOS) presents altered gene expression indicating progesterone resistance and predisposing to reduced endometrial receptivity and endometrial cancer. Objective: We hypothesized that an altered endocrine/metabolic environment in PCOS may result in an endometrial “disease phenotype” affecting the gene expression of different endometrial cell populations, including stem cells and their differentiated progeny. Design and Setting: This was a prospective study conducted at an academic medical center. Patients and Main Outcome Measures: Proliferative-phase endometrium was obtained from 6 overweight/obese PCOS (National Institutes of Health criteria) and 6 overweight/obese controls. Microarray analysis was performed on fluorescence-activated cell sorting-isolated endometrial epithelial cells (eEPs), endothelial cells, stromal fibroblasts (eSFs), and mesenchymal stem cells (eMSCs). Gene expression data were validated using microfluidic quantitative RT-PCR and immunohistochemistry. Results: The comparison between eEPPCOS and eEPCtrl showed dysregulation of inflammatory genes and genes with oncogenic potential (CCL2, IL-6, ORM1, TNAIFP6, SFRP4, SPARC). eSFPCOS and eSFCtrl showed up-regulation of inflammatory genes (C4A/B, CCL2, ICAM1, TNFAIP3). Similarly, in eMSCPCOS vs eMSCCtrl, the most up-regulated genes were related to inflammation and cancer (IL-8, ICAM1, SPRR3, LCN2). Immunohistochemistry scoring showed increased expression of CCL2 in eEPPCOS and eSFPCOS compared with eEPCtrl and eSFCtrl and IL-6 in eEPPCOS compared with eEPCtrl. Conclusions: Isolated endometrial cell populations in women with PCOS showed altered gene expression revealing inflammation and prooncogenic changes, independent of body mass index, especially in eEPPCOS and eMSCPCOS, compared with controls. The study reveals an endometrial disease phenotype in women with PCOS with potential negative effects on endometrial function and long-term health

  8. Study of the Impact of Uterine Artery Embolization (UAE) on Endometrial Microvessel Density (MVD) and Angiogenesis

    SciTech Connect

    Tan Guosheng; Xiang Xianhong; Guo Wenbo; Zhang Bing; Chen Wei; Yang Jianyong

    2013-08-01

    PurposeTo investigate the influence of uterine artery embolization (UAE) on endometrial microvessel density (MVD) and angiogenesis.MethodsSixty female guinea pigs were divided into two groups, the control group (n = 15) and the UAE treatment group (n = 45). In the UAE group, tris-acryl gelatin microspheres were used to generate embolization. Animals were further divided into three subgroups, A1, A2, and A3 (n = 15 for each subgroup), with uterine specimens collected at 7-15, 16-30, and 31-45 days after UAE, respectively. Immunostaining for factor VIII and CD105 was performed to identify total endometrial MVD (MVD{sub FVIII}) and CD105-positive angiogenesis (MVD{sub CD105}) at the indicated time points after UAE.ResultsQuantitative analysis revealed that MVD{sub FVIII} significantly decreased in the A1 (11.40 {+-} 2.76, p < 0.05) and A2 (15.37 {+-} 3.06, p < 0.05) groups compared to the control group (19.40 {+-} 2.50), and was restored to normal in the A3 group (18.77 {+-} 2.69). UAE caused a temporal up-regulation of MVD{sub CD105}-positive angiogenesis in the A1 group (9.33 {+-} 2.37, p < 0.05) and the A2 group (11.63 {+-} 1.56, p < 0.05) compared to the control group (7.12 {+-} 1.67), and the MVD{sub CD105} value returned to normal in the A3 group (8.07 {+-} 1.97).ConclusionUAE caused a temporal decrease in endometrial MVD that reversed over time as a result of the increase of CD105-positive angiogenesis. Although the UAE-induced reduction of endometrial MVD was reversible, its long-term effect on endometrial receptivity still needs further study.

  9. Interfaith Dialogue at Peace Museums in Kenya

    ERIC Educational Resources Information Center

    Gachanga, Timothy; Mutisya, Munuve

    2015-01-01

    This paper makes a case for further studies on the contribution of peace museums to interfaith dialogue debate. Based on our experiences as museum curators, teachers and peace researchers and a review of published materials, we argue that there is a lacuna in the study on the contribution of peace museums to the interfaith dialogue debate. The…

  10. What Makes Dialogues Easy to Understand?

    ERIC Educational Resources Information Center

    Branigan, Holly P.; Catchpole, Ciara M.; Pickering, Martin J.

    2011-01-01

    Two experiments investigate the question of why dialogues tend to be easier for anyone to understand than monologues. One possibility is that overhearers of dialogue have access to the different perspectives provided by the interlocutors, whereas overhearers of monologue have access to the speaker's perspective alone (Fox Tree, 1999). Directors…

  11. The Socratic Dialogue and Teacher Education

    ERIC Educational Resources Information Center

    Knezic, Dubravka; Wubbels, Theo; Elbers, Ed; Hajer, Maaike

    2010-01-01

    This article argues that the Socratic Dialogue in the Nelson and Heckmann tradition will prove a considerable contribution in training teachers. A review of the literature and empirical research supports the claim that the Socratic Dialogue promotes student teachers' interpersonal sensitivity while stimulating conceptual understanding. The article…

  12. The Practice of Dialogue in Critical Pedagogy

    ERIC Educational Resources Information Center

    Kaufmann, Jodi Jan

    2010-01-01

    This paper examines dialogue in the higher education classroom. Instigated by my teaching experiences and the paucity of empirical studies examining dialogue in the higher education classroom, I present a re-examination of data I collected in 1996 for an ethnographic study focusing on the experiences of the participants in an ethnic literature…

  13. Contesting the Constitution: The Constitutional Dialogues.

    ERIC Educational Resources Information Center

    Hilenski, Ferdinand Alexi

    This historical dramatization, prepared for presentation at the 1985 Wyoming Chatauqua, contains three dialogues, set during the administration of President Thomas Jefferson and presenting the issues surrounding the drafting and ratification of the U.S. Constitution. The dialogues are designed to be presented in three segments to permit discussion…

  14. Mining Collaborative Patterns in Tutorial Dialogues

    ERIC Educational Resources Information Center

    D'Mello, Sidney; Olney, Andrew; Person, Natalie

    2010-01-01

    We present a method to automatically detect collaborative patterns of student and tutor dialogue moves. The method identifies significant two-step excitatory transitions between dialogue moves, integrates the transitions into a directed graph representation, and generates and tests data-driven hypotheses from the directed graph. The method was…

  15. Fostering Quality Online Dialogue: Does Labeling Help?

    ERIC Educational Resources Information Center

    Bures, Eva; Abrami, Philip; Schmid, Richard F.

    2010-01-01

    Despite its potential, online dialogue (online dialogue) can be superficial. Following Vygotskian (1978) and design experiment approaches (Brown, 1992), this study explores a labelling feature that allows students to tag parts of their messages. Data comes from 4 sessions of a graduate education course. Students engaged in 2-3 graded online…

  16. Influence in science dialogue: Individual attitude changes as a result of dialogue between laypersons and scientists.

    PubMed

    Zorn, Theodore E; Roper, Juliet; Weaver, C Kay; Rigby, Colleen

    2012-10-01

    Dialogue as a science communication process has been idealized in both practitioner and scholarly literature. However, there is inconsistency in what is meant by dialogue, the forms it should take, and its purported consequences. Empirical research on the experienced benefits of dialogue is limited. The present study addresses this gap by examining attitudinal changes among laypeople and scientists in dialogue on the topic of human biotechnology (HBT). We found that, as a result of participation in dialogue, laypeople's attitudes toward scientists were more positive and scientists' and laypeople's attitudes toward HBT tended to converge. Additionally, laypeople reported increased communicative self-efficacy after the dialogue experience. However, effects in some cases differed by dialogue format. Implications for practice and research are discussed.

  17. Single-cell transcriptome analysis of endometrial tissue

    PubMed Central

    Krjutškov, K.; Katayama, S.; Saare, M.; Vera-Rodriguez, M.; Lubenets, D.; Samuel, K.; Laisk-Podar, T.; Teder, H.; Einarsdottir, E.; Salumets, A.; Kere, J.

    2016-01-01

    commonly expressed genes were detected, with 241 significantly differentially expressed genes. Of these, 231 genes were up- and 10 down-regulated in cultured cells, respectively. In addition, we performed a gene ontology analysis of the differentially expressed genes and found that these genes are mainly related to cell cycle, translational processes and metabolism. LIMITATIONS, REASONS FOR CAUTION Although CD9-positive single epithelial cells sorting was successfully established in our laboratory, the amount of transcriptome data per individual epithelial cell was low, complicating further analysis. This step most likely failed due to the high dose of RNases that are released by the cells' natural processes, or due to rapid turnaround time or the apoptotic conditions in freezing- or single-cell solutions. Since only the cells from the late-secretory phase were subject to more focused analysis, further studies including larger sample size from the different time-points of the natural menstrual cycle are needed. The methodology also needs further optimization to examine different cell types at high quality. WIDER IMPLICATIONS OF THE FINDINGS The symbiosis between clinical biopsy and the sophisticated laboratory and bioinformatic protocols described here brings together clinical diagnostic needs and modern laboratory and bioinformatic solutions, enabling us to implement a precise analytical toolbox for studying the endometrial tissue even at the single-cell level. PMID:26874359

  18. Three dialogues concerning robots in elder care.

    PubMed

    Metzler, Theodore A; Barnes, Susan J

    2014-01-01

    The three dialogues in this contribution concern 21st century application of life-like robots in the care of older adults. They depict conversations set in the near future, involving a philosopher (Dr Phonius) and a nurse (Dr Myloss) who manages care at a large facility for assisted living. In their first dialogue, the speakers discover that their quite different attitudes towards human-robot interaction parallel fundamental differences separating their respective concepts of consciousness. The second dialogue similarly uncovers deeply contrasting notions of personhood that appear to be associated with respective communities of nursing and robotics. The additional key awareness that arises in their final dialogue links applications of life-like robots in the care of older adults with potential transformations in our understandings of ourselves - indeed, in our understandings of the nature of our own humanity. This series of dialogues, therefore, appears to address a topic in nursing philosophy that merits our careful attention.

  19. Endometrial adenocarcinoma in a 13-year-old girl

    PubMed Central

    Kim, Sung Mee; Shin, So Jin; Bae, Jin Gon; Kwon, Kun Young

    2016-01-01

    Endometrial cancer is the third most common gynecologic cancer in the Korea and occurs mainly in menopausal women. Although it can develop in young premenopausal women cancer as well, an attack in the adolescent girl is very rare. A 13-year-old girl visited gynecology department with the complaint of abnormal uterine bleeding. An endometrial biopsy revealed FIGO (International Federation of Gynecology and Obstetrics) grade II endometrial adenocarcinoma. In the treatment of endometrial cancer, conservative management should be considered if the patient is nulliparous or wants the fertility preservation. Therefore, we decided to perform a hormonal therapy and a follow-up endometrial biopsy after progestin administration for eight months revealed no residual tumor. We report a case of endometrial cancer occurred in a 13-year-old girl with a brief review of the literature. PMID:27004208

  20. Detection of endometrial lesions by degree of linear polarization maps

    NASA Astrophysics Data System (ADS)

    Kim, Jihoon; Fazleabas, Asgerally; Walsh, Joseph T.

    2010-02-01

    Endometriosis is one of the most common causes of chronic pelvic pain and infertility and is characterized by the presence of endometrial glands and stroma outside of the uterine cavity. A novel laparoscopic polarization imaging system was designed to detect endometriosis by imaging endometrial lesions. Linearly polarized light with varying incident polarization angles illuminated endometrial lesions. Degree of linear polarization image maps of endometrial lesions were constructed by using remitted polarized light. The image maps were compared with regular laparoscopy image. The degree of linear polarization map contributed to the detection of endometriosis by revealing structures inside the lesion. The utilization of rotating incident polarization angle (IPA) for the linearly polarized light provides extended understanding of endometrial lesions. The developed polarization system with varying IPA and the collected image maps could provide improved characterization of endometrial lesions via higher visibility of the structure of the lesions and thereby improve diagnosis of endometriosis.

  1. Factors affecting intrauterine contraceptive device performance. I. Endometrial cavity length.

    PubMed

    Hasson, H M; Berger, G S; Edelman, D A

    1976-12-15

    The relationship of endometrial cavity length to intrauterine contraceptive device (IUD) performance was evaluated in 319 patients wearing three types of devices. The rate of events, defined as pregnancy, expulsion, or medical removal, increased significantly when the length of the IUD was equal to, exceeded, or was shorter by two or more centimeters than the length of the endometrial cavity. Total uterine length was found to be a less accurate prognostic indicator of IUD performance than endometrial cavity length alone.

  2. MORPHOLOGICAL PATTERN OF ENDOMETRIAL BIOPSIES IN SOUTHWESTERN NIGERIA

    PubMed Central

    Abdullahi, YM; Ajani, MA; Iyapo, O; Aramide, KO; Okolo, CA; Akang, EEU

    2016-01-01

    Background: Endometrium remains the most sensitive indicator of ovarian function and endometrial biopsy is one of the diagnostic procedures in endometrial pathology. The current study was carried out to examine the morphological pattern of endometrial biopsies in Ibadan, South-western Nigeria and compare the results with similar studies. Method: A retrospective study was undertaken to review all cases of endometrial biopsies received in the Department of Pathology, University College Hospital, Ibadan between January 1999 and December 2008. The patients' data were retrieved from the surgical pathology daybooks and Histology Request forms. The neoplastic lesions were classified according to 2003 World Health Organization classification for endometrial neoplasms. Results: A total of 2,444 cases of endometrial biopsies were received during the 10-year study period. The functional endometrial changes were the most common histopathological diagnostic category, accounting for 53.8% (1035) of cases. Other pathological diagnoses included endometritis (7.8%), simple endometrial hyperplasia (5.8%), partial hydatidiform mole (2.3%), complete hydatidiform mole (2.1%) and malignant neoplastic lesions (3.9%). Infertility was the most common (57%) indication for endometrial biopsies followed by uterine bleeding (33%) while the least common clinical indication were the menstrual disorders (10%). Conclusion: The functional endometrial changes account for the highest morphological patterns while malignant lesions account for the least pattern of the endometrial biopsies evaluated for etiological basis of infertility, uterine bleeding and menstrual disorders in Ibadan. Infertility was the commonest indication for endometrial biopsies while the least common clinical indication was menstrual disorders. PMID:28337096

  3. Post-Ablation Endometrial Carcinoma (PAEC) Following Radiofrequency Endometrial Ablation: A Case Report and Its Implications for Management of Endometrial Ablation Failures.

    PubMed

    Wortman, Morris; Dawkins, Josette C

    2016-10-26

    Endometrial ablation (EA) has become one of the most commonly performed gynecologic procedures in the United States and other developed countries. Global endometrial ablation (GEA) devices have supplanted resectoscopic ablation primarily because they have brought with them technical simplicity and unprecedented safety. These devices, all of which received FDA approval between 1997 and 2001, are typically used to treat abnormal uterine bleeding (AUB) in premenopausal women. Several million women in the US who have undergone a previous EA procedure are about to enter the risk pool for the development of endometrial cancer (EC). Ours is the 18th reported case of post-ablation endometrial carcinoma (PAEC) in the English literature. This case underscores the diagnostic challenges faced in evaluating women with a history of a previous EA who cannot be properly evaluated with conventional techniques such as endometrial biopsy and sonohysterography.

  4. PTEN sequence analysis in endometrial hyperplasia and endometrial carcinoma in Slovak women.

    PubMed

    Gbelcová, H; Bakeš, P; Priščáková, P; Šišovský, V; Hojsíková, I; Straka, Ľ; Konečný, M; Markus, J; D'Acunto, C W; Ruml, T; Böhmer, D; Danihel, Ľ; Repiská, V

    2015-01-01

    Phosphatase and tensin homolog (PTEN) is a protein that acts as a tumor suppressor by dephosphorylating the lipid second messenger phosphatidylinositol 3,4,5-trisphosphate. Loss of PTEN function has been implicated in the pathogenesis of a number of different tumors, particularly endometrial carcinoma (ECa). ECa is the most common neoplasia of the female genital tract. Our study evaluates an association between the morphological appearance of endometrial hyperplasia and endometrial carcinoma and the degree of PTEN alterations. A total of 45 endometrial biopsies from Slovak women were included in present study. Formalin-fixed and paraffin-embedded tissue samples with simple hyperplasia (3), complex hyperplasia (5), atypical complex hyperplasia (7), endometrioid carcinomas G1 (20) and G3 (5), and serous carcinoma (5) were evaluated for the presence of mutations in coding regions of PTEN gene, the most frequently mutated tumor suppressor gene in endometrial carcinoma. 75% of the detected mutations were clustered in exons 5 and 8. Out of the 39 mutations detected in 24 cases, 20 were frameshifts and 19 were nonsense, missense, or silent mutations. Some specimens harboured more than one mutation. The results of current study on Slovak women were compared to a previous study performed on Polish population. The two sets of results were similar.

  5. Implantation in the baboon: endometrial responses.

    PubMed

    Fazleabas, A T; Kim, J J; Srinivasan, S; Donnelly, K M; Brudney, A; Jaffe, R C

    1999-01-01

    Blastocyst implantation in the baboon usually occurs between 8 and 10 days post ovulation. Changes that occur within this window of receptivity and immediately following implantation can be divided into three distinct phases. The first phase, regulated by estrogen and progesterone, is characterized primarily by changes in both the luminal and glandular epithelial cells in preparation for blastocyst apposition and attachment. The second phase is the further modulation of these steroid induced changes in both epithelial and stromal cells by embryonic signals. The final phase is associated with trophoblast invasion and the remodeling of the endometrial stromal compartment. During the initial phase, the actions of estrogen and progesterone are dependent on the presence of specific receptors. Estrogen up-regulates both its own receptor (ER) and the progesterone receptor (PR), while progesterone down-regulates this expression pattern. However, the pattern of progesterone-induced down-regulation of ER and PR is confined to the epithelial cells and demonstrates a gradient effect from the functionalis to the basalis. What is most intriguing is that the loss of epithelial PR is closely correlated with the establishment of uterine receptivity. Coincident with the changes in ER and PR expression, epithelial cells undergo alterations in their cytoskeletal architecture and secretory profile. These changes can be counteracted by PR antagonist treatment during the luteal phase. Although estrogen and progesterone play a critical role in establishing the initial phase of uterine receptivity, it is becoming increasingly evident that the embryo induces functional receptivity in ruminants and rodents. In our studies in the primate, we demonstrate that chorionic gonadotrophin when infused in a manner that mimics blastocyst transit, has physiological effects on the three major cell types in the uterine endometrium. The luminal epithelium undergoes endoreplication and distinct epithelial

  6. Osteoporosis is less frequent in endometrial cancer survivors with hypertriglyceridemia.

    PubMed

    Hirasawa, Akira; Makita, Kazuya; Akahane, Tomoko; Yamagami, Wataru; Makabe, Takeshi; Yokota, Megumi; Horiba, Yuko; Ogawa, Mariko; Yanamoto, Shigehisa; Deshimaru, Rhota; Tominaga, Eiichiro; Banno, Kouji; Susumu, Nobuyuki; Aoki, Daisuke

    2015-01-01

    We previously reported an association between dyslipidemia and endometrial cancers. Osteoporosis is also reported to relate with some cancers. A common etiologic event has been proposed between dyslipidemia and osteoporosis. However, the pattern of interrelationships among dyslipidemia, osteoporosis and endometrial cancer is not well understood. To improve the quality of life of endometrial cancer survivors, these relationships should be determined. This study included 179 Japanese menopausal women who underwent bilateral salpingo-oophorectomy, including 114 women with incident endometrial cancer and 65 without endometrial cancer. The women were categorized according to dyslipidemia status. Bone mineral density was measured and compared between groups. Osteoporosis was statistically more frequent in women with hypertriglyceridemia who did not have endometrial cancer. In contrast, osteoporosis was statistically less frequent in women with hypertriglyceridemia who had endometrial cancer. In this cross-sectional study in a Japanese population, osteoporosis was associated with hypertriglyceridemia in post-menopausal women without endometrial cancer, but was less frequent in endometrial cancer survivors with hypertriglyceridemia.

  7. [Epidemiological survey on the relationship between obesity and endometrial cancer].

    PubMed

    Fujimoto, I; Hamada, T; Hasumi, K; Masubuchi, K; Sakamoto, G; Sugano, H

    1986-10-01

    Endometrial carcinoma is found more frequently in obese subjects. In this study, we evaluated the comparative risks of endometrial cancer relative to obesity indices calculated using the Brocas coefficient. From 1979 to 1983, we treated 185 patients with endometrial cancer at the Cancer Institute Hospital, Tokyo. Compared to nonobese subjects, those who exhibited an obesity index of 1.2 or more were found to have a relative risk value of 2.0 or more times that of normal subjects across all age groups. Based on these findings, it is suggested that a practical and effective preventive measure against endometrial cancer is to avoid becoming obese.

  8. Increased TET1 Expression in Inflammatory Microenvironment of Hyperinsulinemia Enhances the Response of Endometrial Cancer to Estrogen by Epigenetic Modulation of GPER

    PubMed Central

    Lv, Qiao-Ying; Xie, Bing-Ying; Yang, Bing-Yi; Ning, Cheng-Cheng; Shan, Wei-Wei; Gu, Chao; Luo, Xue-Zhen; Chen, Xiao-Jun; Zhang, Zhen-Bo; Feng, You-Ji

    2017-01-01

    Background: Insulin resistance (IR) has been well studied in the initiation and development of endometrial endometrioid carcinoma (EEC). As yet, it has been largely neglected for estrogen sensitivity in local endometrium in hyperinsulinemia-induced systemic microenvironment. The aim of this study was to investigate the role of insulin in regulating estrogen sensitivity and explore the potential mechanisms in insulin-driven inflammatory microenvironment. Methods: We first investigated the effect of insulin on estradiol-driven endometrial cancer cells proliferation in vitro to address the roles of insulin in modulating estrogen sensitivity. Then GPER, ERα and TET1 in EEC samples with or without insulin resistance were screened by immunohistochemistry to confirm whether insulin resistance regulates estrogen receptors. Further mechanism analysis was carried out to address whether TET1 was mediated epigenetic modulation of GPER in insulin-induced microenvironment. Results: Insulin enhanced estradiol-driven endometrial cancer cells proliferation by up-regulating G-protein-coupled estrogen receptor (GPER) expression, but not ERα or ERβ. Immunohistochemistry of EEC tissues showed that GPER expression was greatly increased in endometrial tissues from EEC subjects with insulin resistance and was positively correlated with Ten-eleven-translocation 1 (TET1) expression. Mechanistically, insulin up-regulates TET1 expression, and the latter, an important DNA hydroxymethylase, could up-regulate GPER expression through epigenetic modulation. Conclusion: This study identified TET1 as the upstream regulator of GPER expression and provides a possible mechanism that insulin-induced positive regulation of estrogen sensitivity in endometrial cancer cells. Increasing expression of GPER through TET1-mediated epigenetic modulation may emerge as the main regulator to enhance the response of endometrial cancer to estrogen in insulin-driven inflammatory microenvironment. PMID:28382153

  9. Therapeutic doubt and moral dialogue.

    PubMed

    Solbakk, Jan Helge

    2004-02-01

    This paper aims at analysing the problem of remainder and regret in moral conflicts. Four different approaches are subject of investigation: a moral-theoretical strategy aimed at consistency; a narrative approach of moral coherence and open consensus; Plato's moral methodology of dialogue and aporetic resolution of moral conflicts and finally, an approach deduced from Greek tragedy of emotional resolution of moral conflicts. A central argument is that since there exists no theoretically convincing way of solving the problem of remainder and regret, the attention should instead be directed towards finding alternative ways of coping with this problem. The three last approaches subject of investigation attempt--each in their own way--to do this. Teaching medical ethics to medical students and the burning issue of medical fallibility is used to demonstrate the relevance of these forms of resolution in a medical context.

  10. Diabetic nephropathy: a national dialogue.

    PubMed

    Breyer, Matthew D; Coffman, Thomas M; Flessner, Michael F; Fried, Linda F; Harris, Raymond C; Ketchum, Christian J; Kretzler, Matthias; Nelson, Robert G; Sedor, John R; Susztak, Katalin

    2013-09-01

    The National Institute of Diabetes and Digestive and Kidney Diseases-supported Kidney Research National Dialogue (KRND) asked the scientific community to formulate and prioritize research objectives that would improve our understanding of kidney function and disease. Several high-priority objectives for diabetic nephropathy were identified in data and sample collection, hypothesis generation, hypothesis testing, and translation promotion. The lack of readily available human samples linked to comprehensive phenotypic, clinical, and demographic data remains a significant obstacle. With data and biological samples in place, several possibilities exist for using new technologies to develop hypotheses. Testing novel disease mechanisms with state-of-the-art tools should continue to be the foundation of the investigative community. Research must be translated to improve diagnosis and treatment of people. The objectives identified by the KRND provide the research community with future opportunities for improving the prevention, diagnosis, and treatment of diabetic nephropathy.

  11. Immunohistochemical Profiling of Endometrial Serous Carcinoma.

    PubMed

    Chen, Wenqian; Husain, Arjumand; Nelson, Gregg S; Rambau, Peter F; Liu, Shuhong; Lee, Cheng-Han; Lee, Sandra; Duggan, Máire A; Köbel, Martin

    2017-03-01

    Endometrial serous carcinoma (ESC) is an aggressive neoplasm mainly seen in older women. The objective of this study was to refine immunohistochemical (IHC) panels for the differential diagnoses against endometrial endometrioid grade 3 (EC3), endometrial clear cell, and ovarian high-grade serous carcinoma as well as exploring the prognostic role of selected IHC markers. Fifty-two ESC from a single institution were assessed for 20 IHC markers, including ARID1A, CCNE1, CDKN2A, ERBB2, ESR1, HNF1B, FBXW7, IGF2BP3, MLH1, MSH2, MSH6, NAPSA, PAX8, PGR, PMS2, PTEN, TFF3, TP53, VIM, and WT1. ERBB2 chromogenic in situ hybridization was evaluated on tissue microarrays. Statistical analysis was performed. All ESC showed aberrant TP53, normal mismatch repair protein, and retained ARID1A and PTEN expression. ESR1 expression was present in 80% of ESC. A combination of TP53, PTEN, and CDKN2A had a sensitivity of 93.6% [95% confidence interval (CI), 84%-98%] and specificity of 87.8% (95% CI, 75%-95%) for ESC versus EC3. A combination of NAPSA and ESR1 had a sensitivity of 97.9% (95% CI, 89%-99%) and specificity of 72.2% (95% CI, 46%-90%) for ESC versus clear cell carcinoma. Absence of WT1 alone had a sensitivity of 66.0% (95% CI, 51%-79%) and specificity of 98.0% (95% CI, 94%-99%) for ESC versus ovarian high-grade serous carcinoma. Among all 52 ESCs, ERBB2 amplification was present in 23%, FBXW7 expression was absent in 10%, and CCNE1 was overexpressed in 59%, however, none were associated with prognosis. Our data support the value of IHC marker panels for histotyping of high-grade endometrial carcinomas.

  12. Molecular genetic heterogeneity in undifferentiated endometrial carcinomas.

    PubMed

    Rosa-Rosa, Juan M; Leskelä, Susanna; Cristóbal-Lana, Eva; Santón, Almudena; López-García, Ma Ángeles; Muñoz, Gloria; Pérez-Mies, Belen; Biscuola, Michele; Prat, Jaime; Esther, Oliva E; Soslow, Robert A; Matias-Guiu, Xavier; Palacios, Jose

    2016-11-01

    Undifferentiated and dedifferentiated endometrial carcinomas are rare and highly aggressive subtypes of uterine cancer, not well characterized at a molecular level. To investigate whether dedifferentiated carcinomas carry molecular genetic alterations similar to those of pure undifferentiated carcinomas, and to gain insight into the pathogenesis of these tumors, we selected a cohort of 18 undifferentiated endometrial carcinomas, 8 of them with a well-differentiated endometrioid carcinoma component (dedifferentiated endometrioid carcinomas), and studied them by immunohistochemistry and massive parallel and Sanger sequencing. Whole-exome sequencing of the endometrioid and undifferentiated components, as well as normal myometrium, was also carried out in one case. According to The Cancer Genome Atlas classification, we distributed 95% of the undifferentiated carcinomas in this series as follows: (a) hypermutated tumors with loss of any mismatch repair protein expression and microsatellite instability (eight cases, 45%); (b) ultramutated carcinomas carrying mutations in the exonuclease domain of POLE (two cases, 11%); (c) high copy number alterations (copy-number high) tumors group exhibiting only TP53 mutations and high number of alterations detected by FISH (two cases, 11%); and (d) low copy number alterations (copy-number low) tumors with molecular alterations typical of endometrioid endometrial carcinomas (five cases, 28%). Two of the latter cases, however, also had TP53 mutations and higher number of alterations detected by FISH and could have progressed to a copy-number high phenotype. Most dedifferentiated carcinomas belonged to the hypermutated group, whereas pure undifferentiated carcinomas shared molecular genetic alterations with copy-number low or copy-number high tumors. These results indicate that undifferentiated and dedifferentiated endometrial carcinomas are molecularly heterogeneous tumors, which may have prognostic value.

  13. A New Diagnostic Test for Endometrial Cancer?

    PubMed Central

    Guralp, Onur; Sheridan, Susan M.; Harter, Josephine; Hinshaw, James Louis; Seo, Songwon; Hartenbach, Ellen M.; Lindheim, Steven; Stewar, Sarah; Kushner, David M.

    2014-01-01

    Objective During saline-infused sonohysterography (SIS), the distension fluid is typically discarded. If cytology analysis could identify those patients with endometrial cancer, many women would be spared from further procedures. Methods Thirty consecutive patients with clinical stage I or II endometrial adenocarcinoma were prospectively recruited preoperatively. Saline-infused sonohysterography was performed by instilling 5 mL of saline, withdrawing and sending for analysis. Saline was reinfused until complete SIS images were obtained and sent separately for cytology. Results Of the 30 women enrolled, SIS was technically successful in 29. Demographics included mean age (60.5 ± 6.99 years), body mass index (35.55 ± 8.18 kg/m2), endometrioid histology (76%), and grade (grade 1, 67%). Prestudy diagnostic method included biopsy (70%), dilatation and curettage (17%), and hysteroscopy (10%). Adequate cytology specimens were obtained in 66% of the 5mL flushes and 72% of the complete SIS collections. Of adequate specimens, the sensitivities to detect endometrial cancer for the 5-mL, complete, and combined fluid samples were 26% (95% confidence interval, 9%–51%), 36% (17%–59%), and 42% (22%–63%). Sensitivity based on the whole study sample (N = 30) was 33% (17%–53%). Statistical significance was not found in the association between a positive test and age, body mass index, grade, diagnostic method, or volume instilled or aspirated. Conclusions Most patients with early endometrial cancer can undergo SIS procedures with adequate cytology specimens obtained from distention media. However, the sensitivity is low, and refinements are necessary before utilizing as a diagnostic test. In cases with positive results, the patient may be able to avoid other costly and painful procedures. PMID:23881100

  14. Type II endometrial cancers: A case series

    PubMed Central

    Lobo, Flora D.; Thomas, Eliz

    2016-01-01

    Introduction: Endometrial carcinoma ranks 3rd in India among gynecological malignancies. Endometrial cancer (EC) can be classified into two distinct groups – type I and type II, based on histology, which differs in molecular, clinical and histopathological profiles. Type II is nonestrogen dependent, nonendometrioid, more aggressive and carries poor prognosis. Although type II cancers contribute only about 10% of EC incidence, they present at advanced age and cause approximately 50% recurrence and deaths with a low 5-year, overall survival rate. Type II EC are also characterized by genetic alterations in p53, human epidermal growth factor-2/neu, p16 and E-cadherin. Materials and Methods: Endometrial carcinomas diagnosed from endometrial biopsies and hysterectomy specimens received in the Department of Pathology, Kasturba Medical College, Mangalore, from January 2007 to June 2012 were included in the study. Clinicopathological analysis of the 84 cases of EC was done with emphasis on morphology. p53 immunostaining was performed in two cases of serous carcinoma. Results: Out of a total of 84 cases of EC, ten cases were of type II (11.9%). Out of which, eight were serous carcinoma (9.5%) and two clear cell (2.4%). p53 immunostain was strongly positive in the serous papillary carcinomas. The age of the patients ranged from 45 to 75 years. Myometrial invasion was more than half. Treatment was hysterectomy followed by aggressive chemotherapy. Conclusion: Of the type II EC, serous carcinoma is the most common type. Clinical presentation and prognosis differs in comparison to type I EC, thus the recognition of this type of EC is pivotal. PMID:27499593

  15. Endometrial cancer and microsatellite instability status

    PubMed Central

    Vidugiriene, Jolanta; Valuckas, Konstantinas Povilas; Smailyte, Giedre; Uleckiene, Saule; Bacher, Jeff

    2015-01-01

    Microsatellite instability (MSI) is an important factor in the development of various cancers as an identifier of a defective DNA mismatch repair system. The objective of our study was to define the association between microsatellite instability status and traditional clinicopathologic characteristics of endometrioid type adenocarcinoma. Material and methods MSI status of endometrial cancer was examined by employing the Promega MSI Analysis System. This system uses 5 mononucleotide markers to identify MSI in tumour and normal tissue DNA (BAT-25, BAT-26, NR-21, NR-24, and MONO-27), and 2 pentanucleotide markers (Penta C and Penta D) for specimen identification. In this study, we investigated MSI status in 109 endometrial carcinomas. Results and conclusions One hundred (92%) of 109 endometrial cancers showed endometrioid type histology and only 9 (8%) non-endometrioid type. MSI-high was found in 17% (17/100) of endometrioid type adenocarcinomas, in 0% (0/9) of non-endometrioid carcinomas. Selected clinicopathologic parameters for endometrioid type adenocarcinomas were compared to the MSI status which was separated into two groups – MSI-high and MSI stable. The results showed that MSI-high status was related to clinicopathologic parameters such as deep myometrial invasion and higher histologic grade in endometrioid type adenocarcinomas.

  16. Integrated Genomic Characterization of Endometrial Carcinoma

    PubMed Central

    2013-01-01

    Summary We performed an integrated genomic, transcriptomic, and proteomic characterization of 373 endometrial carcinomas using array- and sequencing-based technologies. Uterine serous tumors and ~25% of high-grade endometrioid tumors have extensive copy number alterations, few DNA methylation changes, low ER/PR levels, and frequent TP53 mutations. Most endometrioid tumors have few copy number alterations or TP53 mutations but frequent mutations in PTEN, CTNNB1, PIK3CA, ARID1A, KRAS and novel mutations in the SWI/SNF gene ARID5B. A subset of endometrioid tumors we identified had a dramatically increased transversion mutation frequency, and newly identified hotspot mutations in POLE. Our results classified endometrial cancers into four categories: POLE ultramutated, microsatellite instability hypermutated, copy number low, and copy number high. Uterine serous carcinomas share genomic features with ovarian serous and basal-like breast carcinomas. We demonstrated that the genomic features of endometrial carcinomas permit a reclassification that may impact post-surgical adjuvant treatment for women with aggressive tumors. PMID:23636398

  17. Nrf2 expression in endometrial serous carcinomas and its precancers.

    PubMed

    Chen, Ning; Yi, Xiaofang; Abushahin, Nisreen; Pang, Shujie; Zhang, Donna; Kong, Beihua; Zheng, Wenxin

    2010-12-24

    Endometrial serous carcinoma (ESC) is the most aggressive subtype of endometrial cancer. Its aggressive behavior and poor clinical outcome may be partially attributed to lack of early diagnostic markers and unclear patho-genesis. The transcription factor Erythroid-E2-related factor 2 (Nrf2) is a recently identified protein marker, which plays a role in carcinogenesis as well as responsible for poor prognosis of many human cancers. The aim of this study is to determine the Nrf2 expression in benign endometrium (n=28), endometrial cancers (n=122) as well as their precursor lesions (n=81) trying to see whether Nrf2 has any diagnostic usage and is potentially involved in endometrial carcinogenesis. The level of Nrf2 was evaluated by immunohistochemical (IHC) and verified by using Western blots. Among the malignant cases, Nrf2 was positive in 28 (68%) of 50 ESCs, which was significantly more than in 3 (6%) of 50 endometrioid carcinomas (p < 0.001) and 2 (13%) of 15 clear cell carcinomas (p = 0.001) and other histologic types of endometrial cancers. Among endometrial precursor lesions, both serous endometrial glandular dysplasia (EmGD, 40%) and serous endometrial intraepithelial carcinoma (EIC, 44%) showed a significantly higher Nrf2 expression than that in atypical endometrial hyperplasia or endometrial intraepithelial neoplasia (0%), clear cell EmGD (10%), and clear cell EIC (25%), respectively. We conclude that Nrf2 overexpression is closely associated with endometrial neoplasms with serous differentiation. Alteration of Nrf2 expression may represent one of the early molecular events in ESC carcinogenesis and overexpression of Nrf2 may used as a diagnostic marker in surgical pathology.

  18. Anti-proliferative effects of Siegesbeckia orientalis ethanol extract on human endometrial RL-95 cancer cells.

    PubMed

    Chang, Chi-Chang; Hsu, Hsia-Fen; Huang, Kuo-Hung; Wu, Jing-Mei; Kuo, Shyh-Ming; Ling, Xue-Hua; Houng, Jer-Yiing

    2014-12-01

    Endometrial cancer is a common malignancy of the female genital tract. This study demonstrates that Siegesbeckia orientalis ethanol extract (SOE) significantly inhibited the proliferation of RL95-2 human endometrial cancer cells. Treating RL95-2 cells with SOE caused cell arrest in the G2/M phase and induced apoptosis of RL95-2 cells by up-regulating Bad, Bak and Bax protein expression and down-regulation of Bcl-2 and Bcl-xL protein expression. Treatment with SOE increased protein expression of caspase-3, -8 and -9 dose-dependently, indicating that apoptosis was through the intrinsic and extrinsic apoptotic pathways. Moreover, SOE was also effective against A549 (lung cancer), Hep G2 (hepatoma), FaDu (pharynx squamous cancer), MDA-MB-231 (breast cancer), and especially on LNCaP (prostate cancer) cell lines. In total, 10 constituents of SOE were identified by Gas chromatography-mass analysis. Caryophyllene oxide and caryophyllene are largely responsible for most cytotoxic activity of SOE against RL95-2 cells. Overall, this study suggests that SOE is a promising anticancer agent for treating endometrial cancer.

  19. The G protein-coupled receptor GPR30 mediates the proliferative and invasive effects induced by hydroxytamoxifen in endometrial cancer cells

    SciTech Connect

    Du, Gui-Qiang; Zhou, Long; Chen, Xiao-Yue; Wan, Xiao-Ping; He, Yin-Yan

    2012-04-06

    Highlights: Black-Right-Pointing-Pointer We assessed hydroxytamoxifen (OHT) effects in two endometrial cancer cell lines. Black-Right-Pointing-Pointer GPR30 mediates the proliferative effects induced by OHT. Black-Right-Pointing-Pointer GPR30 mediates the invasive effects induced by OHT. Black-Right-Pointing-Pointer GPR30 expression was up-regulated by OHT in endometrial cancer cell line. -- Abstract: The selective ER modulator tamoxifen (TAM) is the most widely used ER antagonist for treatment of women with hormone-dependent breast tumor. However, long-term treatment is associated with an increased risk of endometrial cancer. The aim of the present study was to demonstrate new insight into the role of G-protein coupled receptor 30 (GPR30) in the activity of TAM, which promoted endometrial cancer. In endometrial cancer cell lines ISHIKAWA and KLE, the potential of 4-hydroxytamoxifen (OHT), the active metabolite of TAM, 17{beta}-estradiol (E2) and G1, a non-steroidal GPR30-specific agonist to promote cell proliferation and invasion was evaluated. All agents above induced high proliferative and invasive effects, while the down-regulation of GPR30 or the interruption of MAPK signal pathway partly or completely prevented the action of the regent. Moreover, the RNA and protein expression of GPR30 was up-regulated by G1, E2 or OHT in both cell lines. The present study provided a new insight into the mechanism involved in the agonistic activity exerted by TAM in the uterus.

  20. Endometrial Adenocarcinoma Presenting in a Premenopausal Patient with Tuberous Sclerosis

    ERIC Educational Resources Information Center

    Jaffe, J. S.; Chambers, J. T.

    2005-01-01

    Background: Endometrial adenocarcinoma is very uncommon in women under 40 years of age. Case: A 39-year-old woman with tuberous sclerosis and severe intellectual disability presented with irregular bleeding unresponsive to oral contraceptive therapy. She was subsequently found to have a deeply invasive endometrial adenocarcinoma. Conclusion:…

  1. Human Endometrial CD98 Is Essential for Blastocyst Adhesion

    PubMed Central

    Domínguez, Francisco; Simón, Carlos; Quiñonero, Alicia; Ramírez, Miguel Ángel; González-Muñoz, Elena; Burghardt, Hans; Cervero, Ana; Martínez, Sebastián; Pellicer, Antonio; Palacín, Manuel; Sánchez-Madrid, Francisco; Yáñez-Mó, María

    2010-01-01

    Background Understanding the molecular basis of embryonic implantation is of great clinical and biological relevance. Little is currently known about the adhesion receptors that determine endometrial receptivity for embryonic implantation in humans. Methods and Principal Findings Using two human endometrial cell lines characterized by low and high receptivity, we identified the membrane receptor CD98 as a novel molecule selectively and significantly associated with the receptive phenotype. In human endometrial samples, CD98 was the only molecule studied whose expression was restricted to the implantation window in human endometrial tissue. CD98 expression was restricted to the apical surface and included in tetraspanin-enriched microdomains of primary endometrial epithelial cells, as demonstrated by the biochemical association between CD98 and tetraspanin CD9. CD98 expression was induced in vitro by treatment of primary endometrial epithelial cells with human chorionic gonadotropin, 17-β-estradiol, LIF or EGF. Endometrial overexpression of CD98 or tetraspanin CD9 greatly enhanced mouse blastocyst adhesion, while their siRNA-mediated depletion reduced the blastocyst adhesion rate. Conclusions These results indicate that CD98, a component of tetraspanin-enriched microdomains, appears to be an important determinant of human endometrial receptivity during the implantation window. PMID:20976164

  2. Entropy growth in emotional online dialogues

    NASA Astrophysics Data System (ADS)

    Sienkiewicz, J.; Skowron, M.; Paltoglou, G.; Hołyst, Janusz A.

    2013-02-01

    We analyze emotionally annotated massive data from IRC (Internet Relay Chat) and model the dialogues between its participants by assuming that the driving force for the discussion is the entropy growth of emotional probability distribution.

  3. The perioperative dialogue: holistic nursing in practice.

    PubMed

    Rudolfsson, Gudrun; von Post, Iréne; Eriksson, Katie

    2007-01-01

    This article is a synthesis of 2 qualitative studies focusing on patients', anesthetists', and operating-room nurses' experiences of the perioperative dialogue and employing grounded theory as the method of analysis. The aim of the synthesis was to achieve a new holistic understanding of health in the perioperative dialogue. The synthesis highlights the importance of being in communion in a continuous whole due to continuity of care for the creation of health in both patients and nurses.

  4. Endometrial MicroRNA Signature during the Window of Implantation Changed in Patients with Repeated Implantation Failure

    PubMed Central

    Shi, Cheng; Shen, Huan; Fan, Li-Juan; Guan, Jing; Zheng, Xin-Bang; Chen, Xi; Liang, Rong; Zhang, Xiao-Wei; Cui, Qing-Hua; Sun, Kun-Kun; Zhao, Zhu-Ran; Han, Hong-Jing

    2017-01-01

    Background: At present, a diagnostic tool with high specificity for impaired endometrial receptivity, which may lead to implantation failure, remains to be developed. We aimed to assess the different endometrial microRNA (miRNA) signatures for impaired endometrial receptivity by microarray analysis. Methods: A total of 12 repeated implantation failure (RIF) patients and 10 infertile patients, who conceived and delivered after one embryo transfer attempt, were recruited as RIF and control groups, respectively. Endometrial specimens from the window of implantation (WOI) were collected from these two groups. MiRNA microarray was conducted on seven and five samples from the RIF and control groups, respectively. Comparative, functional, and network analyses were performed for the microarray results. Quantitative real-time polymerase chain reaction (PCR) was performed on other samples to validate the expression of specific miRNAs. Results: Compared with those in the control group, the expression levels of 105 miRNAs in the RIF group were found to be significantly up- or down-regulated (at least 2-fold) by microarray analysis. The most relevant miRNA functional sets of these dysregulated miRNAs were miR-30 family, human embryonic stem cell regulation, epithelial-mesenchymal transition, and miRNA tumor suppressors by tool for annotations of microRNA analysis. Network regulatory analysis found 176 miRNA-mRNA interactions, and the top 3 core miRNAs were has-miR-4668-5p, has-miR-429, and has-miR-5088. Expression levels of the 18 selected miRNAs in new samples by real-time PCR were found to be regulated with the same trend, as the result of microarray analysis. Conclusions: There is a significant different expression of certain miRNAs in the WOI endometrium for RIF patients. These miRNAs may contribute to impaired endometrial receptivity. PMID:28229988

  5. Transcriptional response of the bovine endometrium and embryo to endometrial polymorphonuclear neutrophil infiltration as an indicator of subclinical inflammation of the uterine environment.

    PubMed

    Hoelker, Michael; Salilew-Wondim, Dessie; Drillich, Marc; Christine, Grosse-Brinkhaus; Ghanem, Nasser; Goetze, Leopold; Tesfaye, Dawit; Schellander, Karl; Heuwieser, Wolfgang

    2012-01-01

    The aim of the present study was to analyse the effect of subclinical endometritis on endometrial and embryonic gene expression. A total of 49 cows at either Day 0 or Day 7 of the oestrous cycle (62-83 days post partum) following superovulation were classified as having subclinical endometritis (SE-0, SE-7) or a healthy endometrium (HE-0, HE-7) on the basis of endometrial cytological evaluation. Endometrial samples and associated embryos were subjected to global transcriptome analysis using the Bovine GeneChip (Affymetrix, Santa Clara, CA, USA) and aberrant transcript profiles were observed in SE-0 and SE-7 cows. At Day 0, 10 transcripts were found to be differentially expressed in endometrial samples. Specifically, the PDZK1, PXDN, DDHD2, GPLD1 and SULT1B1 genes were downregulated, whereas the PKIB, LOC534256, BT29392, LYZ and S100A14 genes were upregulated in SE-0 cows. Similarly, 11 transcripts were found to be differentially regulated on Day 7. Of these, GNPTG, BOLA-DQA5, CHD2, LOC541226, VCAM1 and ARHGEF2 were found to be downregulated, whereas PSTPIP2, BT236441 and MGC166084 were upregulated in SE-7 cows. Accordingly, endometrial health status affected the number of flushed, transferable embryos. In all, 20 genes were differentially regulated in blastocysts derived from HE-7 and SE-7 cows. Of these, GZMK, TCEAL4, MYL7, ADD3 and THEM50B were upregulated, whereas NUDCD2, MYO1E, BZW1, EHD4 and GZMB were downregulated. In conclusion, endometrial polymorphonuclear neutrophil infiltration as an indicator of subclinical endometritis is associated with changes in endometrial gene expression patterns, including genes involved in cell adhesion and immune modulation. Consequently, subclinical endometritis affects gene expression in embryos, including the expression of genes related to membrane stability, the cell cycle and apoptosis.

  6. Group dialogue empowers Brazilian women.

    PubMed

    Badiani, R; Becker, J

    1995-11-01

    In response to an alarming rise in human immunodeficiency virus (HIV) infection among Brazilian women during the early 1990s, the Sociedade Civil Bem-Estar Familiar no Brazil (BEMFAM) developed a project that integrates HIV prevention with clinical services, community-based prevention activities, and sexually transmitted disease diagnosis and treatment. Preliminary interviews with clinic clients revealed that women's fears they would be considered unfaithful were impeding their ability to suggest condom use to their sexual partners. Condom use within a relationship was considered appropriate only for pregnancy prevention. To facilitate dialogue about sexual health, BEMFAM developed a women's group intervention project. All women who attend a BEMFAM clinic are invited to participate in a one-hour group discussion before receiving medical services. Novela-style booklets with stories and characters women can relate to their own lives are used to stimulate discussion. Participants learn to use condoms correctly by putting them on a penis model and anticipate situations in which they would be able to negotiate condom use. The group setting enables women to gain confidence and practice assertiveness in a non-threatening, supportive environment. Their identification with other women's stories empowers women to take control of their health and sexual lives. Between October 1994 and July 1995, 3464 women participated in group discussions organized by BEMFAM and 40,688 condoms were distributed; 18% of these women returned to the clinic for additional condoms.

  7. Overexpression of progesterone receptor A isoform in mice leads to endometrial hyperproliferation, hyperplasia and atypia.

    PubMed

    Fleisch, M C; Chou, Y C; Cardiff, Robert D; Asaithambi, A; Shyamala, G

    2009-04-01

    A delicate balance in estrogen and progesterone signaling through their cognate receptors is characteristic for the physiologic state of the endometrium, and a shift in receptor isotype expression can be frequently found in human endometrial pathology. In this study, using a transgenic mouse model, we examined the mechanisms whereby alterations in progesterone receptor (PR) isotype expression leads to endometrial pathology. For an experimental model, we used transgenic mice (PR-A transgenics) carrying an imbalance in the native ratio of the two PR isoforms A and B (PR-A and PR-B) through the expression of additional A form and examined their uterine phenotype under different hormonal regimens, using various criteria. Uterine epithelial cell proliferation was augmented in PR-A transgenics and was abolished by PR antagonists. In particular, proliferative response to progesterone, independent of signaling through estrogen, was enhanced. Upon continuous exposure to estradiol and progesterone, the uteri in PR-A transgenics displayed gross enlargement, endometrial hyperplasia including atypical lesions, endometritis and pelvic inflammatory disease. Imbalanced expression of the two isoforms of PR in a transgenic model reveals multiple derangements in the regulation of uterine physiology, resulting in various pathologies including hyperplasias.

  8. Social Software for Reflective Dialogue: Questions about Reflection and Dialogue in Student Teachers' Blogs

    ERIC Educational Resources Information Center

    Granberg, Carina

    2010-01-01

    This article presents a study of 57 Swedish pre-school student teachers' experiences and achievements in using blogs for reflective dialogue over the course of 2007-2008. In order to examine the extent to which students engaged in reflective dialogue, text analyses of their blogs were carried out. Furthermore, 13 narrative interviews were…

  9. Isolated humeral recurrence in endometrial carcinoma

    PubMed Central

    Devdas, Santosh Kumar; Digumarti, Leela; Digumarti, Raghunadharao; Patro, Kunha Charan; Nutakki, Ramakoteswararao

    2016-01-01

    Isolated skeletal metastasis in endometrial carcinoma at recurrence is very rare. We report a 52-year-old woman diagnosed to have FIGO Stage 1b, Grade 1 endometrioid adenocarcinoma, presenting with isolated distal humerus metastasis, 2 years after surgery and adjuvant radiotherapy for primary disease. Imaging, bone scintigraphy, and cytology confirmed the diagnosis of poorly differentiated metastatic adenocarcinoma. She was treated with local radiotherapy followed by six cycles of paclitaxel and carboplatin chemotherapy along with zoledronic acid, monthly. She is symptom-free after the treatment and at a first follow-up visit after 3 months. PMID:27688615

  10. Centchroman induces redox-dependent apoptosis and cell-cycle arrest in human endometrial cancer cells.

    PubMed

    Shyam, Hari; Singh, Neetu; Kaushik, Shweta; Sharma, Ramesh; Balapure, Anil K

    2017-04-01

    Centchroman (CC) or Ormeloxifene has been shown to induce apoptosis and cell cycle arrest in various types of cancer cells. This has, however, not been addressed for endometrial cancer cells where its (CC) mechanism of action remains unclear. This study focuses on the basis of antineoplasticity of CC by blocking the targets involved in the cell cycle, survival and apoptosis in endometrial cancer cells. Ishikawa Human Endometrial Cancer Cells were cultured under estrogen deprived medium, exposed to CC and analyzed for proliferation and apoptosis. Additionally, we also analyzed oxidative stress induced by CC. Cell viability studies confirmed the IC50 of CC in Ishikawa cells to be 20 µM after 48 h treatment. CC arrests the cells in G0/G1 phase through cyclin D1 and cyclin E mediated pathways. Phosphatidylserine externalization, nuclear morphology changes, DNA fragmentation, PARP cleavage, and alteration of Bcl-2 family protein expression clearly suggest ongoing apoptosis in the CC treated cells. Activation of caspase 3 & 9, up-regulation of AIF and inhibition of apoptosis by z-VAD-fmk clearly explains the participation of the intrinsic pathway of programmed cell death. Further, the increase of ROS, loss of MMP, inhibition of antioxidant (MnSOD, Cu/Zn-SOD and GST) and inhibition of apoptosis with L-NAC suggests CC induced oxidative stress leading to apoptosis via mitochondria mediated pathway. Therefore, CC could be a potential therapeutic agent for the treatment of Endometrial Cancer adjunct to its utility as a contraceptive and an anti-breast cancer agent.

  11. DNA damage and apoptosis of endometrial cells cause loss of the early embryo in mice exposed to carbon disulfide

    SciTech Connect

    Zhang, Bingzhen; Shen, Chunzi; Yang, Liu; Li, Chunhui; Yi, Anji; Wang, Zhiping

    2013-12-01

    Carbon disulfide (CS{sub 2}) may lead to spontaneous abortion and very early pregnancy loss in women exposed in the workplace, but the mechanism remains unclear. We designed an animal model in which gestating Kunming strain mice were exposed to CS{sub 2} via i.p. on gestational day 4 (GD4). We found that the number of implanted blastocysts on GD8 was significantly reduced by each dose of 0.1 LD{sub 50} (157.85 mg/kg), 0.2 LD{sub 50} (315.7 mg/kg) and 0.4 LD{sub 50} (631.4 mg/kg). In addition, both the level of DNA damage and apoptosis rates of endometrial cells on GD4.5 were increased, showed definite dose–response relationships, and inversely related to the number of implanted blastocysts. The expressions of mRNA and protein for the Bax and caspase-3 genes in the uterine tissues on GD4.5 were up-regulated, while the expressions of mRNA and protein for the Bcl-2 gene were dose-dependently down-regulated. Our results indicated that DNA damage and apoptosis of endometrial cells were important reasons for the loss of implanted blastocysts induced by CS{sub 2}. - Highlights: • We built an animal model of CS2 exposure during blastocyst implantation. • Endometrial cells were used in the comet assay to detect DNA damage. • CS2 exposure caused DNA damage and endometrial cell apoptosis. • DNA damage and endometrial cell apoptosis were responsible for embryo loss.

  12. Effects of genistein in combination with conjugated estrogens on endometrial hyperplasia and metabolic dysfunction in ovariectomized mice.

    PubMed

    Kim, Jun Ho; Kim, Young Jun

    2015-01-01

    Tissue-selective estrogen complex (TSEC), which combines a selective estrogen receptor modulator (SERM) with one or more estrogens, is a novel approach to menopausal therapy. It has been demonstrated that the phytoestrogen genistein (GEN) exhibits mixed estrogen receptor agonist and antagonist activity, suggesting that GEN may have potential for use as a natural SERM. We evaluated, for the first time, the effects of GEN, conjugated estrogens (CE), and their pairing effects as a TSEC treatment on estrogen-induced endometrial hyperplasia and metabolic dysfunction in ovariectomized (OVX) mice fed a high-fat diet. CE replacement prevented fat accumulation in the adipose tissue and liver, improved glucose homeostasis, and induced endometrial hyperplasia in OVX mice. GEN at 100 mg/kg showed CE mimetic effects in preventing ovariectomy-induced metabolic dysfunctions without endometrial stimulation. Combination treatments with CE and GEN prevented metabolic dysfunctions more strongly than CE alone, but at both low and high doses, GEN did not reverse CE-induced endometrial hyperplasia. In addition, we found that in a TSEC regimen, a typical SERM raloxifene maintains the metabolic benefits of CE while simultaneously protecting the endometrium in OVX mice. These findings indicate that GEN acts as an estrogen agonist in metabolic regulation, but has no SERM function in the uteri of OVX mice.

  13. Differential Expression and Clinical Significance of DNA Methyltransferase 3B (DNMT3B), Phosphatase and Tensin Homolog (PTEN) and Human MutL Homologs 1 (hMLH1) in Endometrial Carcinomas.

    PubMed

    Li, Wenting; Wang, Ying; Fang, Xinzhi; Zhou, Mei; Li, Yiqun; Dong, Ying; Wang, Ruozheng

    2017-02-21

    BACKGROUND The aim of this study was to investigate the expression and the clinicopathologic significance of DNA methyltransferase 3B (DNMT3B), phosphatase and tensin homolog (PTEN) and human MutL homologs 1 (hMLH1) in endometrial carcinomas between Han and Uygur women in Xinjiang. MATERIAL AND METHODS The expression of DNMT3B, PTEN, and hMLH1 in endometrial carcinomas were assessed by immunohistochemistry, followed by an analysis of their relationship to clinical-pathological features and prognosis. RESULTS There were a 61.7% (95/154) overexpression of DNMT3B, 50.0% (77/154) loss of PTEN expression and 18.2% (28/154) loss of hMLH1 expression. The expression of DNMT3B and PTEN in endometrial carcinomas was statistically significantly different between Uygur women and Han women (p=0.001, p=0.010, respectively). DNMT3B expression was statistically significant based on the grade of endometrial carcinomas (p=0.031). PTEN loss was statistically significant between endometrioid carcinomas (ECs) and non endometrioid carcinomas (NECs) (p=0.040). DNMT3B expression was statistically significant in different myometrial invasion groups in Uygur women (p=0.010). Furthermore, the correlation of DNMT3B and PTEN expression was significant in endometrial carcinomas (p=0.021). PTEN expression was statistically significant in the overall survival (OS) rate of women with endometrial cancers (p=0.041). CONCLUSIONS Our findings suggest that PTEN and DNMT3B possess common regulation features as well as certain ethnic differences in expression between Han women and Uygur women. An interaction may exist in the pathogenesis of endometrial carcinoma. DNMT3B was expressed differently in cases of myometrial invasion and PTEN was associated with OS, which suggested that these molecular markers may be useful in the evaluation of the biological behavior of endometrial carcinomas and may be useful indicators of prognosis in women with endometrial carcinomas.

  14. [Environmental and genetic risk factors for endometrial carcinoma].

    PubMed

    Sénéchal, Claire; Cottereau, Edouard; de Pauw, Antoine; Elan, Camille; Dagousset, Isabelle; Fourchotte, Virginie; Gauthier-Villars, Marion; Lae, Marick; Stoppa-Lyonnet, Dominique; Buecher, Bruno

    2015-03-01

    In France, endometrial cancer is at the first rank of gynecological cancers for cancer incidence, before ovarian and cervical cancers. In fact, the number of incident cases has been estimated to 7275 for the year 2012; the number of death due to endometrial cancer to 2025. This cancer is hormone-dependent and endogenous (reproductive factors) or exogenous (oral combined contraceptives, hormone replacement therapy) causes of exposition to estrogens are the major environmental risk factors for both types of endometrial cancers: type I or well-differentiated endometrioid adenocarcinomas; and type II including all other histological types: papillary serous adenocarcinomas, clear cell adenocarcinomas and carcinosarcomas, also known as malignant mixed Mullerian tumor, MMMT. Obesity, diabetes mellitus and adjuvant treatment of breast cancer with tamoxifen are also associated with an increased risk of endometrial cancer. Genetic factors may also be implicated in the pathogenesis of endometrial cancer either as "minor genetic factors" (susceptibility factors), which remain largely unknown and are responsible for the increased observed risk in relatives of women affected with endometrial cancer; or as major genetic factors responsible for hereditary forms and namely for Lynch syndrome whose genetic transmission is of autosomic dominant type. The appropriate recognition of Lynch syndrome is of critical importance because affected patients and their relatives should benefit from specific care. The aims of this review is to describe major environmental and genetic risk factors for endometrial cancer with specific attention to most recent advances in this field and to describe recommendations for care of at-risk women.

  15. Endometrial transcriptome in recurrent miscarriage and recurrent implantation failure.

    PubMed

    Huang, Jin; Qin, Hao; Yang, Yihua; Chen, Xiaoyan; Zhang, Jiamiao; Laird, Susan; Wang, Chi Chiu; Chan, Ting Fung; Li, Tin Chiu

    2017-03-10

    The endometrium becomes receptive to the embryo only in the mid-luteal phase, but not other stages of the menstrual cycle. Endometrial factors play an important role in implantation. Women with recurrent miscarriage and recurrent implantation failure have both been reported to have altered expression of receptivity markers during the window of implantation. We aimed to compare the gene expression profiles of the endometrium in the window of implantation among women with unexplained recurrent implantation failures (RIF) and unexplained recurrent miscarriages (RM) by RNA sequencing (RNA-Seq). In total 20 patients (9 RIF and 11 RM) were recruited. In addition 4 fertile subjects were included as reference. Endometrium samples were precisely timed on the 7th day after luteal hormone surge (LH+7). All the 24 samples were extracted for total RNA. The transcriptome was determined by RNA-Seq in first 14 RNA samples (5 RIF, 6 RM, and 3 fertile). Differentially expressed genes between RM and RIF were validated by quantitative real time PCR (qPCR) in all 24 RNA samples (9 RIF, 11 RM and 4 fertile). Complementary and coagulation cascades pathway was the significantly up-regulated in RIF while down-regulated in RM. Differentially expressed genes C3, C4, C4BP, DAF, DF and SERPING1 in complement and coagulation cascade pathway between RM and RIF were further validated by qPCR. This study identified differential molecular pathways in endometrium between RIF and RM, which potentially affect the implantation process.

  16. Obesity-related hormones and endometrial cancer among postmenopausal women: a nested case-control study within the B~FIT cohort.

    PubMed

    Dallal, Cher M; Brinton, Louise A; Bauer, Douglas C; Buist, Diana S M; Cauley, Jane A; Hue, Trisha F; Lacroix, Andrea; Tice, Jeffrey A; Chia, Victoria M; Falk, Roni; Pfeiffer, Ruth; Pollak, Michael; Veenstra, Timothy D; Xu, Xia; Lacey, James V

    2013-02-01

    Endometrial cancer risk is strongly influenced by obesity, but the mechanisms of action remain unclear. Leptin and adiponectin, secreted from adipose tissue, reportedly play a role in such carcinogenic processes as cell proliferation, angiogenesis, and insulin regulation. In this case-control study, nested within the Breast and Bone Follow-up of the Fracture Intervention Trial (n=15,595), we assessed pre-diagnostic serum leptin, total adiponectin, and high-molecular-weight (HMW) adiponectin in relation to endometrial cancer among postmenopausal women. During the 10-year follow-up, 62 incident endometrial cases were identified and matched to 124 controls on age, geographical site, time of fasting blood draw at baseline (1992-1993), and trial participation status. Adipokines and C-peptide were measured by ELISA. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated via conditional logistic regression, with exposures categorized in tertiles (T). Multivariable models considered C-peptide, BMI (kg/m(2)), and estradiol (E2) as potential confounders. Endometrial cancer risk was significantly associated with higher leptin levels, adjusted for E2 and C-peptide (OR(T3 vs T1)=2.96; 95% CI, 1.21-7.25; P trend <0.01). After further adjustment for BMI, the estimates were attenuated and the positive trend was no longer statistically significant (OR(T3 vs T1)=2.11; 95% CI, 0.69-6.44; P trend=0.18). No significant associations were observed with adiponectin or HMW adiponectin and endometrial cancer. Our findings with leptin suggest that the leptin-BMI axis might increase endometrial cancer risk through mechanisms other than estrogen-driven proliferation. Continued exploration of these pathways in larger prospective studies may help elucidate mechanisms underlying observed obesity-endometrial cancer associations.

  17. A prospective investigation of coffee drinking and endometrial cancer incidence.

    PubMed

    Gunter, Marc J; Schaub, Jennifer A; Xue, Xiaonan; Freedman, Neal D; Gaudet, Mia M; Rohan, Thomas E; Hollenbeck, Albert R; Sinha, Rashmi

    2012-08-15

    Coffee drinking may be associated with reduced risk of endometrial cancer; however, prospective data are limited. Further, it is not clear whether any association between coffee and endometrial cancer differs according to coffee caffeine content. The association of coffee drinking with incidence of endometrial cancer was evaluated among 226,732 women, aged 50-71, enrolled in the NIH-AARP Diet and Health Study who completed a baseline epidemiologic questionnaire. Following a mean 9.3 years of follow-up, data were available for 1,486 incident endometrial cancer cases. Cox proportional hazards models were used to estimate associations of coffee with endometrial cancer incidence. Sub-group analyses were performed according to smoking status, hormone therapy use (HT) and body habitus. Coffee drinking was inversely related to incidence of endometrial cancer (hazard ratio [HR] comparing drinking of >3 cups/day versus no cups = 0.64, 95% CI, 0.51-0.80; P(trend) = 0.0004). The association of coffee with endometrial cancer risk was apparent for consumption of both regular (HR per cup = 0.90, 95% CI, 0.86-0.95) and decaffeinated coffee (HR per cup = 0.93, 95% CI, 0.87-0.99). The relation of coffee with endometrial cancer incidence varied significantly by HT use (P(interaction) = 0.03) with an association only apparent among HT-never users (HR comparing drinking >3 cups/day versus no cups = 0.54, 95% CI, 0.41-0.72; P(trend) = 0.0005). Endometrial cancer incidence appears to be reduced among women that habitually drink coffee, an association that does not differ according to caffeine content.

  18. Endometrial factors similarly induced by IFNT2 and IFNTc1 through transcription factor FOXS1.

    PubMed

    Kusama, Kazuya; Bai, Rulan; Nakamura, Keigo; Okada, Sayaka; Yasuda, Jiro; Imakawa, Kazuhiko

    2017-01-01

    In ruminants, Interferon tau (IFNT) is the pregnancy recognition protein produced by the mononuclear trophectoderm of the conceptus, and is secreted into the uterine lumen during the peri-attachment period. In our previous study, the high-throughput RNA sequencing (RNA-seq) data obtained from bovine conceptuses during the peri-attachment period identified two IFNT mRNAs, IFNT2 and IFNTc1. However, how each of these IFNT variants regulates endometrial gene expression has not been characterized. Using RNA-seq analysis, we evaluated how IFNT2 and IFNTc1 affected transcript expression in primary bovine endometrial epithelial cells (EECs). IFNT treatment induced 348 differentially expressed genes (DEGs); however, there are few DEGs in IFNT2 or IFNTc1 treated EECs, indicating that IFNT2-induced DEGs were similar to those induced by IFNTc1 treatment. In in silico analysis, we identified four IFNT2- and IFNTc1-induced pathways: 1) type II interferon signaling, 2) proteasome degradation, 3) type III interferon signaling, and 4) DNA damage response. We further demonstrated that IFNT2 and IFNTc1 up-regulated several transcription factors, among which forkhead box S1 (FOXS1) was identified as the most highly expressed gene. Furthermore, the knockdown of FOXS1 in IFNT2- or IFNTc1-treated EECs similarly down-regulated 9 genes including IRF3 and IRF9, and up-regulated 9 genes including STAT1, STAT2, and IRF8. These represent the first demonstration that effects of each IFNT on EECs were studied, and suggest that endometrial response as well as signaling mechanisms were similar between two IFNT variants existed in utero.

  19. Identifying diagnostic endocrine markers and changes in endometrial gene expressions during pyometra in cats.

    PubMed

    Jursza-Piotrowska, Ewelina; Siemieniuch, Marta J

    2016-06-01

    Pyometra is a significant reproductive problem in cats. The aims of this study were to evaluate (i) the immunological profile of queens by studying plasma concentrations of metabolites of prostacyclin I2 (6-keto-PGF1α), leukotriene B4 (LTB4) and leukotriene C4 (LTC4); and (ii) the gene transcription profiles of Toll-like receptors (TLRs) 2 and 4 (TLR2/4), PGE2-synthase (PGES), PGF2α-synthase (PGFS) and prostaglandin-endoperoxide synthase 2 (PTGS2) in the feline endometrium throughout the estrous cycle, after medroxyprogesterone acetate (MPA) treatment and during pyometra. The concentration of plasma 6-keto-PGF1α in pyometra was increased in comparison to other groups studied (p<0.01). Endometrial mRNA coding for TLR2 was up-regulated in cats suffering from pyometra compared to other groups (p<0.001). Expression of mRNA for TLR4 was up-regulated in endometria originating from MPA-treated cats, pyometra and late diestrus cats, compared with tissues from cats during estrus and anestrus (p<0.05). As expected, endometrial mRNA for PTGS2 was up-regulated only in pyometra, compared with other groups (p<0.001). Similarly, endometrial mRNA for PGFS was up-regulated in pyometra, compared with endometria from anestrus, late diestrus and from MPA-treated cats (p<0.05), or from cats during estrus (p<0.01). Overall, these results indicate that plasma concentrations of LTB4 and LTC4 are not useful diagnostic markers since they were not increased in queens with pyometra, in contrast to 6-keto-PGF1α. In addition, treatment with MPA evoked neither endocrine nor molecular changes in endometria of cats.

  20. Endometrial factors similarly induced by IFNT2 and IFNTc1 through transcription factor FOXS1

    PubMed Central

    Kusama, Kazuya; Bai, Rulan; Nakamura, Keigo; Okada, Sayaka; Yasuda, Jiro; Imakawa, Kazuhiko

    2017-01-01

    In ruminants, Interferon tau (IFNT) is the pregnancy recognition protein produced by the mononuclear trophectoderm of the conceptus, and is secreted into the uterine lumen during the peri-attachment period. In our previous study, the high-throughput RNA sequencing (RNA-seq) data obtained from bovine conceptuses during the peri-attachment period identified two IFNT mRNAs, IFNT2 and IFNTc1. However, how each of these IFNT variants regulates endometrial gene expression has not been characterized. Using RNA-seq analysis, we evaluated how IFNT2 and IFNTc1 affected transcript expression in primary bovine endometrial epithelial cells (EECs). IFNT treatment induced 348 differentially expressed genes (DEGs); however, there are few DEGs in IFNT2 or IFNTc1 treated EECs, indicating that IFNT2-induced DEGs were similar to those induced by IFNTc1 treatment. In in silico analysis, we identified four IFNT2- and IFNTc1-induced pathways: 1) type II interferon signaling, 2) proteasome degradation, 3) type III interferon signaling, and 4) DNA damage response. We further demonstrated that IFNT2 and IFNTc1 up-regulated several transcription factors, among which forkhead box S1 (FOXS1) was identified as the most highly expressed gene. Furthermore, the knockdown of FOXS1 in IFNT2- or IFNTc1-treated EECs similarly down-regulated 9 genes including IRF3 and IRF9, and up-regulated 9 genes including STAT1, STAT2, and IRF8. These represent the first demonstration that effects of each IFNT on EECs were studied, and suggest that endometrial response as well as signaling mechanisms were similar between two IFNT variants existed in utero. PMID:28199372

  1. Therapeutic options for management of endometrial hyperplasia.

    PubMed

    Chandra, Vishal; Kim, Jong Joo; Benbrook, Doris Mangiaracina; Dwivedi, Anila; Rai, Rajani

    2016-01-01

    Endometrial hyperplasia (EH) comprises a spectrum of changes in the endometrium ranging from a slightly disordered pattern that exaggerates the alterations seen in the late proliferative phase of the menstrual cycle to irregular, hyperchromatic lesions that are similar to endometrioid adenocarcinoma. Generally, EH is caused by continuous exposure of estrogen unopposed by progesterone, polycystic ovary syndrome, tamoxifen, or hormone replacement therapy. Since it can progress, or often occur coincidentally with endometrial carcinoma, EH is of clinical importance, and the reversion of hyperplasia to normal endometrium represents the key conservative treatment for prevention of the development of adenocarcinoma. Presently, cyclic progestin or hysterectomy constitutes the major treatment option for EH without or with atypia, respectively. However, clinical trials of hormonal therapies and definitive standard treatments remain to be established for the management of EH. Moreover, therapeutic options for EH patients who wish to preserve fertility are challenging and require nonsurgical management. Therefore, future studies should focus on evaluation of new treatment strategies and novel compounds that could simultaneously target pathways involved in the pathogenesis of estradiol-induced EH. Novel therapeutic agents precisely targeting the inhibition of estrogen receptor, growth factor receptors, and signal transduction pathways are likely to constitute an optimal approach for treatment of EH.

  2. Therapeutic options for management of endometrial hyperplasia

    PubMed Central

    2016-01-01

    Endometrial hyperplasia (EH) comprises a spectrum of changes in the endometrium ranging from a slightly disordered pattern that exaggerates the alterations seen in the late proliferative phase of the menstrual cycle to irregular, hyperchromatic lesions that are similar to endometrioid adenocarcinoma. Generally, EH is caused by continuous exposure of estrogen unopposed by progesterone, polycystic ovary syndrome, tamoxifen, or hormone replacement therapy. Since it can progress, or often occur coincidentally with endometrial carcinoma, EH is of clinical importance, and the reversion of hyperplasia to normal endometrium represents the key conservative treatment for prevention of the development of adenocarcinoma. Presently, cyclic progestin or hysterectomy constitutes the major treatment option for EH without or with atypia, respectively. However, clinical trials of hormonal therapies and definitive standard treatments remain to be established for the management of EH. Moreover, therapeutic options for EH patients who wish to preserve fertility are challenging and require nonsurgical management. Therefore, future studies should focus on evaluation of new treatment strategies and novel compounds that could simultaneously target pathways involved in the pathogenesis of estradiol-induced EH. Novel therapeutic agents precisely targeting the inhibition of estrogen receptor, growth factor receptors, and signal transduction pathways are likely to constitute an optimal approach for treatment of EH. PMID:26463434

  3. Dilatation and Curettage Effect on the Endometrial Thickness

    PubMed Central

    Davar, Robab; Dehghani Firouzabadi, Razieh; Chaman Ara, Kefayat

    2013-01-01

    Background Endometrial receptivity is required for successful implantation and pregnancy. Despite the remaining controversy, many studies have shown that ultrasonographic endometrial thickness can be considered as an indicator of endometrial receptivity. Objective The study objective was to investigate the effect of dilatation and curettage on the endometrial thickness. Materials and Methods Enrolled in the study were 444 patients visited in Obstetrics & Gynecology clinic of Shahid Sadoughi hospital between Jan. 2011 to Sep. 2012. Only patients whose menstrual cycle was regular were included in study. Patients with myoma, adenomyosis, endometrial polyps or other uterine anomaly, those who smoked, whose BMI was greater than 30 and who were taking medications that could affect endometrial thickness were excluded. Endometrial thickness was measured one day before evolution (n = 444) and 5-7 days after it (n = 444) using transvaginal ultrasonography. The endometrial thicknesses were correlated to the patients’ history of dilatation and curettage. Data analysis was done through SPSS software version 16 and using descriptive statistics, independent T-test and Anova. Results Endometrial thickness in patients who had 0, 1, 2, 3 and 4 D&C were 10.00 ± 0.58, 9.83 ± 0.47, 8.90 ± 0.92, 7.42 ± 0.18 and 7.40 ± 0.07, respectively one day before ovulation (spearman’s correlation coefficient = -0.33) and 10.62 ± 0.68, 9.64 ± 0.49, 8.48 ± 0.96, 6.32 ± 0.15 and 6.90 ± 0.04, respectively, 5-7 days after ovulation (spearman’s correlation coefficient = -0.66) estradiol and progesterone levels, measured in the day of 2nd ultrasonography had not statistic relation with endometrial thickness (P = 0.27 and 0.31). The relation of endometrial thickness and age was not significant (P = 0.54 and 0.06). Conclusions Dilatation and curettage has a significant effect on the endometrial thinning. PMID:24083012

  4. Endometrial biopsy interpretation. Shortcomings and problems in current gynecologic practice.

    PubMed

    Van Bogaert, L J; Maldague, P; Staquet, J P

    1978-01-01

    The analysis of 345 endometrial biopsies was carried out with special regard to the relation between pathologic findings and presenting symptoms or complaints. Only 52.4% of the biopsies showed microscopic features possibly related to the complaints. Endometrial polyps and chronic endometritis were diagnosed in 21.1 and 9.8%, respectively, of the entire study group. The currently accepted definitions of dysfunctional uterine bleeding raise the question whether endometrial polyps and atypical secretory changes may or may not be included in the syndrome.

  5. Quantum Secure Dialogue with Quantum Encryption

    NASA Astrophysics Data System (ADS)

    Ye, Tian-Yu

    2014-09-01

    How to solve the information leakage problem has become the research focus of quantum dialogue. In this paper, in order to overcome the information leakage problem in quantum dialogue, a novel approach for sharing the initial quantum state privately between communicators, i.e., quantum encryption sharing, is proposed by utilizing the idea of quantum encryption. The proposed protocol uses EPR pairs as the private quantum key to encrypt and decrypt the traveling photons, which can be repeatedly used after rotation. Due to quantum encryption sharing, the public announcement on the state of the initial quantum state is omitted, thus the information leakage problem is overcome. The information-theoretical efficiency of the proposed protocol is nearly 100%, much higher than previous information leakage resistant quantum dialogue protocols. Moreover, the proposed protocol only needs single-photon measurements and nearly uses single photons as quantum resource so that it is convenient to implement in practice.

  6. Race talk: the psychology of racial dialogues.

    PubMed

    Sue, Derald Wing

    2013-11-01

    Constructive dialogues on race have been proposed as a means to heal racial and ethnic divides, reduce prejudice and misinformation, increase racial literacy, and foster improved race relations. Studies on the psychology of racial dialogues indicate social and academic norms that dictate against race talk between White Americans and persons of color: (a) the politeness protocol, (b) the academic protocol, and (c) the color-blind protocol. These protocols discourage race talk and allow society to enter into a conspiracy of silence regarding the detrimental impact oppression plays on persons of color. Facilitating difficult dialogues on race requires educators to recognize what makes such discussions difficult. For people of color, engaging in race talk exposes them to microaggressions that invalidate and assail their racial/ethnic identities. For Whites, honest discussions are impeded by fears of appearing racist, of realizing their racism, of acknowledging White privilege, and of taking responsibility to combat racism.

  7. The Human Communication Research Centre dialogue database.

    PubMed

    Anderson, A H; Garrod, S C; Clark, A; Boyle, E; Mullin, J

    1992-10-01

    The HCRC dialogue database consists of over 700 transcribed and coded dialogues from pairs of speakers aged from seven to fourteen. The speakers are recorded while tackling co-operative problem-solving tasks and the same pairs of speakers are recorded over two years tackling 10 different versions of our two tasks. In addition there are over 200 dialogues recorded between pairs of undergraduate speakers engaged on versions of the same tasks. Access to the database, and to its accompanying custom-built search software, is available electronically over the JANET system by contacting liz@psy.glasgow.ac.uk, from whom further information about the database and a user's guide to the database can be obtained.

  8. Adenovirus mediated homozygous endometrial epithelial Pten deletion results in aggressive endometrial carcinoma

    SciTech Connect

    Joshi, Ayesha; Ellenson, Lora Hedrick

    2011-07-01

    Pten is the most frequently mutated gene in uterine endometriod carcinoma (UEC) and its precursor complex atypical hyperplasia (CAH). Because the mutation frequency is similar in CAH and UEC, Pten mutations are thought to occur relatively early in endometrial tumorigenesis. Previous work from our laboratory using the Pten{sup +/-} mouse model has demonstrated somatic inactivation of the wild type allele of Pten in both CAH and UEC. In the present study, we injected adenoviruses expressing Cre into the uterine lumen of adult Pten floxed mice in an attempt to somatically delete both alleles of Pten specifically in the endometrium. Our results demonstrate that biallelic inactivation of Pten results in an increased incidence of carcinoma as compared to the Pten{sup +/-} mouse model. In addition, the carcinomas were more aggressive with extension beyond the uterus into adjacent tissues and were associated with decreased expression of nuclear ER{alpha} as compared to associated CAH. Primary cultures of epithelial and stromal cells were prepared from uteri of Pten floxed mice and Pten was deleted in vitro using Cre expressing adenovirus. Pten deletion was evident in both the epithelial and stromal cells and the treatment of the primary cultures with estrogen had different effects on Akt activation as well as Cyclin D3 expression in the two purified components. This study demonstrates that somatic biallelic inactivation of Pten in endometrial epithelium in vivo results in an increased incidence and aggressiveness of endometrial carcinoma compared to mice carrying a germline deletion of one allele and provides an important in vivo and in vitro model system for understanding the genetic underpinnings of endometrial carcinoma.

  9. Leptin upregulates beta3-integrin expression and interleukin-1beta, upregulates leptin and leptin receptor expression in human endometrial epithelial cell cultures.

    PubMed

    Gonzalez, R R; Leavis, P

    2001-10-01

    Human endometrium and endometrial epithelial cells (EECs) either cultured alone or cocultured with human embryos express leptin and leptin receptor. This study compares the effect of leptin with that of interleukin-1beta (IL-1beta) on the expression of beta3-EEC integrin, a marker of endometrial receptivity. Both cytokines increased the expression of beta3-EEC at concentrations in the range of 0.06-3 nM; however, leptin exhibited a significantly greater effect than IL-1beta. We also determined the regulatory effects of IL-1beta on leptin secretion and on the expression of leptin and leptin receptor at the protein level in both EEC and endometrial stromal cell (ESC) cultures. In EEC cultures, IL-1beta upregulated secretion of leptin and expression of both leptin and leptin receptors. No effect of IL-1beta was found in the ESC cultures. However, leptin exhibited marginal upregulation of leptin receptor. The upregulation of beta3-integrin and leptin/leptin receptor expression by IL-1beta in EEC cultures indicates that both cytokines may be implicated in embryonic-maternal cross-talk during the early phase of human implantation. Our present data also raise the possibility that leptin is an endometrial molecular effector of IL-1beta action on beta3-integrin upregulation. Thus, a new role for leptin in human reproduction as an autocrine/paracrine regulator of endometrial receptivity is proposed.

  10. A peptide derived from the human leptin molecule is a potent inhibitor of the leptin receptor function in rabbit endometrial cells.

    PubMed

    Gonzalez, Ruben Rene; Leavis, Paul C

    2003-07-01

    In this article we show that rabbit endometrial cells express leptin receptor and that human leptin triggers phosphorylation of signal transducer and activator of transcription 3 and up-regulates the expression of interleukin- 1 receptor type I as was previously found in human endometrial cells. Interestingly, leptin also upregulates the secretion of leukemia inhibitory factor and expression of its receptor by rabbit endometrial cells. Analysis of a structural model of the leptin-leptin receptor complex suggested that helices I and III of the human leptin structure were likely sites of interaction with the cytokine binding domain of leptin receptor. Accordingly, we synthesized a peptide (LPA-2) comprising helix III (residues 70-95) and investigated its ability to inhibit leptin receptor function. The effects of LPA-2 were assayed in rabbit endometrial cells, and an antileptin receptor antibody and a scrambled version of LPA-2 were used as positive and negative controls, respectively. LPA-2 binds specifically and with high affinity (Ki ~ 0.6 x 10-10 M) to leptin receptor and is a potent inhibitor of its functions in rabbit endometrial cells. Because leukemia inhibitory factor and interleukin- 1 have been implicated in embryo implantation, our results raise the possibility that the LPA-2-induced inhibition of leptin receptor may be exploited to study the actions of leptin in endometrium and in other tissues under conditions characterized by abnormal leptin production.

  11. Interfaith Dialogue as a Means for Transformational Conversations

    ERIC Educational Resources Information Center

    Krebs, Stephanie Russell

    2015-01-01

    This article reports findings, inspired by the researcher's personal, transformational experience, on students' responses to an interfaith dialogue at an Interfaith Youth Core Interfaith Leadership Institute. Results demonstrated that several factors characterize interfaith dialogue: the environment, individual relationships fostered through…

  12. Aurora kinase A has a significant role as a therapeutic target and clinical biomarker in endometrial cancer.

    PubMed

    Umene, Kiyoko; Yanokura, Megumi; Banno, Kouji; Irie, Haruko; Adachi, Masataka; Iida, Miho; Nakamura, Kanako; Nogami, Yuya; Masuda, Kenta; Kobayashi, Yusuke; Tominaga, Eiichiro; Aoki, Daisuke

    2015-04-01

    Aurora kinase A (AURKA) regulates the cell cycle checkpoint and maintains genomic integrity. AURKA is overexpressed in various malignant tumors and its upregulation induces chromosomal instability, which leads to aneuploidy and cell transformation. To investigate the role of AURKA in endometrial cancer, we evaluated the association of immunohistochemical expression of AURKA with clinicopathological factors. Furthermore, we examined the effects of AURKA inhibition by transfected siRNA in HEC-1B cells on colony-forming ability, invasion and migration capacity, and chemosensitivity. Immunohistochemical staining showed that overexpression of AURKA was significantly associated with tumor grade (P<0.05) and poor histologic differentiation (P<0.05). The recurrence rate also tended to be high in cases with overexpression of AURKA (P<0.1) and these cases also had a tendency for shorter disease-free survival (DFS) (P<0.1). AURKA inhibition in endometrial cancer cell lines significantly decreased cell growth, invasion and migration (P<0.05), and increased chemosensitivity to paclitaxel. We also evaluated the efficacy of a combination of AURKA siRNA and paclitaxel against subcutaneous tumors formed in a nude mouse. After treatment, the tumor volume shrank significantly compared to treatment with paclitaxel only (P<0.05). To our knowledge, this is the first study in endometrial carcinoma to show a correlation between overexpression of AURKA and tumor grade, histological type and sensitivity to paclitaxel. AURKA is a promising therapeutic target in endometrial cancer and the combination therapy with AURKA inhibitors and paclitaxel could be effective for endometrial cancer that is resistant to conventional treatment and has a poor prognosis.

  13. Epidemiology of Endometrial Cancer Consortium (E2C2)

    Cancer.gov

    The Epidemiology of Endometrial Cancer Consortium studies the etiology of this common cancer and build on resources from existing studies by combining data across studies in order to advance the understanding of the etiology of this disease.

  14. [Current possibilities of examination and preservative treatment in endometrial hyperplasia].

    PubMed

    Kołodziejczak, Małgorzata; Knapp, Paweł; Kuźmicki, Mariusz; Knapp, Piotr

    2011-07-01

    Endometrial hyperplasia is one of the most frequent reasons of pre- and menopausal bleeding. In recent years, knowledge of biology of hyperplastic endometrium has changed some medical guidelines in a group of patients diagnosed with endometrial lesions. In many cases radical procedures have been replaced with preservative treatment, especially for those women who wished to spare their uterus. Also, in many high-risk surgical procedures there are a number of algorithms which allow to perform non-radical treatment in those cases. Enforcement of those strategy should be linked to precise examination of endometrium morphology Summarizing, a preservative treatment in case of endometrial hyperplasia needs sensitive and specific tests which determine safety limits of the procedure. This paper has presented current possibilities of examination and non-radical treatment of endometrial hyperplasia.

  15. Endometrial Adenocarcinoma in a 27-Year-Old Woman

    PubMed Central

    Fadhlaoui, Anis; Ben Hassouna, Jamel; Khrouf, Mohamed; Zhioua, Fethi; Chaker, Anis

    2010-01-01

    Background Endometrial adenocarcinoma usually occurs after menopause, but in 2%–14% of cases, it occurs in young patients (less than 40 years of age) who are eager to preserve their fertility. Its treatment includes hysterectomy, bilateral salpingo-oophorectomy and pelvic lymphadenectomy, and, in some cases, radiation therapy. Aim To describe a case of endometrial adenocarcinoma occurring in a young woman and to undertake a literature review of risk factors and therapeutic options proposed for young women wishing to preserve their fertility. Case We report a case of endometrial cancer in a 27-year-old woman treated for resistant menorrhagia and cared for in our department as well as in the Salah Azaiez Institute. Conclusion Endometrial adenocarcinoma rarely occurs in young women. In such cases, other therapeutic options can be proposed: progesterone therapy and LH-RH (Luteinzing-Hormone-Releasing-Hormone) agonists therapy in order to preserve fertility in younger patients. PMID:21769252

  16. Endometrial and acute myeloid leukemia cancer genomes characterized

    Cancer.gov

    Two studies from The Cancer Genome Atlas (TCGA) program reveal details about the genomic landscapes of acute myeloid leukemia (AML) and endometrial cancer. Both provide new insights into the molecular underpinnings of these cancers.

  17. Factors Influencing Endometrial Thickness in Postmenopausal Women

    PubMed Central

    Hebbar, S; Chaya, V; Rai, L; Ramachandran, A

    2014-01-01

    Background: Cut-off values for endometrial thickness (ET) in asymptomatic postmenopausal woman have been standardized. However, there are no comprehensive studies to document how various factors can influence the ET after the age of menopause. Aim: To study the various factors influencing the ET in postmenopausal women. Subjects and Methods: This was a prospective observational study. A total of 110 postmenopausal women underwent detailed history taking, clinical examination, and transvaginal scan for uterine volume and ovarian volume. The volumes were calculated by using ellipsoid formula: Width × thickness × height × 0.523. The variation in ET with respect to the influencing factors such as age, duration of menopause, parity, body mass index (BMI), medical illness like diabetes/hypertension, drugs like tamoxifen, presence of myoma, uterine volume, ovarian volume, and serum estradiol (in selected patients) were measured. Descriptive analysis was performed using SPSS software (version 16, Chicago II, USA) to obtain mean, standard deviation (SD), 95% confidence intervals (CIs) and inter quartile ranges. Comparison of means was carried out using analysis of variance. Results: The mean (SD) age of the patients was 55.4 (6.91) years (95% CI, 54.1, 56.7). The mean (SD) age at menopause was 47.95 (3.90) years (95% CI, 47.2, 48.7) and the mean (SD) duration of menopause was 7.27 (6.65) years (95% CI, 6.01, 8.53). The mean (SD) ET was 3.8 (2.3) mm (95% CI, 3.36, 4.23). Medical illness like diabetes and hypertension did not alter the ET. ET increased as BMI increased and it was statistically significant. The presence of myoma increased uterine volume significantly and was associated with thick endometrial stripe. Similarly, whenever the ovaries were visualized and as the ovarian volume increased, there was an increase in ET. When ET was > 4 mm (n = 37), they were offered endocel, of which 16 agreed to undergo the procedure. None were found to have endometrial cancer

  18. Reflective Scientific Sense-Making Dialogue in Two Languages: The Science in the Dialogue and the Dialogue in the Science

    ERIC Educational Resources Information Center

    Ash, Doris

    2004-01-01

    In this paper I focus on the transition from everyday to scientific ways of reasoning, and on the intertwined roles of meaning-making dialogue and science content as they contribute to scientific literacy. I refer to views of science, and how scientific understanding is advanced dialogically, by Hurd (Science Education, 1998, 82, 402-416), Brown…

  19. Regulatory Action of Calcium Ion on Cyclic AMP-Enhanced Expression of Implantation-Related Factors in Human Endometrial Cells

    PubMed Central

    Kusama, Kazuya; Yoshie, Mikihiro; Tamura, Kazuhiro; Imakawa, Kazuhiko; Isaka, Keiichi; Tachikawa, Eiichi

    2015-01-01

    Decidualization of human endometrial stroma and gland development is mediated through cyclic AMP (cAMP), but the role of intracellular calcium ion (Ca2+) on cAMP mediated-signaling in human endometrial stroma and glandular epithelia has not been well-characterized. The present study was designed to investigate the role of intracellular Ca2+ on cAMP mediated-decidualization and gland maturation events, which can be identified by the up-regulation of prolactin and IGF-binding protein (IGFBP)1 in human endometrial stromal cells (ESCs), and cyclooxygenase 2 (COX2) and prostaglandin E2 (PGE2) and glandular epithelial EM-1 cells. Increases in decidual prolactin and IGFBP-1 transcript levels, induced by cAMP-elevating agents forskolin or dibutyryl cyclic AMP, were inhibited by Ca2+ influx into ESCs with Ca2+ ionophores (alamethicin, ionomycin) in a dose-dependent manner. Conversely, inhibitors of Ca2+ influx through L-type voltage-dependent Ca2+ channel (VDCC), nifedipine and verapamil, enhanced the decidual gene expression. Furthermore, dantrolene, an inhibitor of Ca2+ release from the intracellular Ca2+ store, up-regulated prolactin and IGFBP-1 expression. Ca2+ ionophores decreased intracellular cAMP concentrations, whereas nifedipine, verapamil or dantrolene increased cAMP concentrations in ESCs. In glandular epithelial cells, similar responses in COX2 expression and PGE2 production were found when intracellular cAMP levels were up-regulated by decreases in Ca2+ concentrations. Thus, a marked decrease in cytosolic Ca2+ levels caused the elevation of cAMP concentrations, resulting in enhanced expression of implantation-related factors including decidual markers. These findings suggest that fluctuation in cytosolic Ca2+ concentrations alters intracellular cAMP levels, which then regulate differentiation of endometrial stromal and glandular epithelial cells. PMID:26161798

  20. Regulatory Action of Calcium Ion on Cyclic AMP-Enhanced Expression of Implantation-Related Factors in Human Endometrial Cells.

    PubMed

    Kusama, Kazuya; Yoshie, Mikihiro; Tamura, Kazuhiro; Imakawa, Kazuhiko; Isaka, Keiichi; Tachikawa, Eiichi

    2015-01-01

    Decidualization of human endometrial stroma and gland development is mediated through cyclic AMP (cAMP), but the role of intracellular calcium ion (Ca2+) on cAMP mediated-signaling in human endometrial stroma and glandular epithelia has not been well-characterized. The present study was designed to investigate the role of intracellular Ca2+ on cAMP mediated-decidualization and gland maturation events, which can be identified by the up-regulation of prolactin and IGF-binding protein (IGFBP)1 in human endometrial stromal cells (ESCs), and cyclooxygenase 2 (COX2) and prostaglandin E2 (PGE2) and glandular epithelial EM-1 cells. Increases in decidual prolactin and IGFBP-1 transcript levels, induced by cAMP-elevating agents forskolin or dibutyryl cyclic AMP, were inhibited by Ca2+ influx into ESCs with Ca2+ ionophores (alamethicin, ionomycin) in a dose-dependent manner. Conversely, inhibitors of Ca2+ influx through L-type voltage-dependent Ca2+ channel (VDCC), nifedipine and verapamil, enhanced the decidual gene expression. Furthermore, dantrolene, an inhibitor of Ca2+ release from the intracellular Ca2+ store, up-regulated prolactin and IGFBP-1 expression. Ca2+ ionophores decreased intracellular cAMP concentrations, whereas nifedipine, verapamil or dantrolene increased cAMP concentrations in ESCs. In glandular epithelial cells, similar responses in COX2 expression and PGE2 production were found when intracellular cAMP levels were up-regulated by decreases in Ca2+ concentrations. Thus, a marked decrease in cytosolic Ca2+ levels caused the elevation of cAMP concentrations, resulting in enhanced expression of implantation-related factors including decidual markers. These findings suggest that fluctuation in cytosolic Ca2+ concentrations alters intracellular cAMP levels, which then regulate differentiation of endometrial stromal and glandular epithelial cells.

  1. Dialogue and Its Conditions: The Construction of European Citizenship

    ERIC Educational Resources Information Center

    Hodgson, Naomi

    2011-01-01

    The Council of Europe's "White Paper on Intercultural Dialogue" provides an example of the way in which dialogue has become part of the current mode of governance in Europe. Throughout current policy, the terms "dialogue" and "voice" inform the introduction of practices and tools that constitute the citizen, or active learning citizen. Notions of…

  2. Language Facilities for Programming User-Computer Dialogues.

    ERIC Educational Resources Information Center

    Lafuente, J. M.; Gries, D.

    1978-01-01

    Proposes extensions to PASCAL that provide for programing man-computer dialogues. An interactive dialogue application program is viewed as a sequence of frames and separate computational steps. PASCAL extensions allow the description of the items of information in each frame and the inclusion of behavior rules specifying the interactive dialogue.…

  3. Three Modes of Dialogue about Works of Art

    ERIC Educational Resources Information Center

    Hubard, Olga M.

    2010-01-01

    Over the last two decades, art teachers and museum educators have increasingly embraced group dialogue to help students make meaning from works of art. To an outside observer, most dialogues about art could appear to be the same. Nevertheless, careful analysis reveals that the spirit and dynamics can differ greatly from one dialogue to the next.…

  4. Automatic Dialogue Scoring for a Second Language Learning System

    ERIC Educational Resources Information Center

    Huang, Jin-Xia; Lee, Kyung-Soon; Kwon, Oh-Woog; Kim, Young-Kil

    2016-01-01

    This paper presents an automatic dialogue scoring approach for a Dialogue-Based Computer-Assisted Language Learning (DB-CALL) system, which helps users learn language via interactive conversations. The system produces overall feedback according to dialogue scoring to help the learner know which parts should be more focused on. The scoring measures…

  5. Studying and Facilitating Dialogue in Select Online Management Courses

    ERIC Educational Resources Information Center

    Ivancevich, John M.; Gilbert, Jacqueline A.; Konopaske, Robert

    2009-01-01

    Dialogue is arguably one of the most significant elements of learning in higher education. The premise of this article is that online instructors can creatively facilitate dialogue for effectively teaching online management courses. This article presents a dialogue-focused framework for addressing significant behavioral, structural, and…

  6. Dialogue-Based CALL: An Overview of Existing Research

    ERIC Educational Resources Information Center

    Bibauw, Serge; François, Thomas; Desmet, Piet

    2015-01-01

    Dialogue-based Computer-Assisted Language Learning (CALL) covers applications and systems allowing a learner to practice the target language in a meaning-focused conversational activity with an automated agent. We first present a common definition for dialogue-based CALL, based on three features: dialogue as the activity unit, computer as the…

  7. Persistence of endometrial activity after radiation therapy for cervical carcinoma

    SciTech Connect

    Barnhill, D.; Heller, P.; Dames, J.; Hoskins, W.; Gallup, D.; Park, R.

    1985-12-01

    Radiation therapy is a proved treatment for cervical carcinoma; however, it destroys ovarian function and has been thought to ablate the endometrium. Estrogen replacement therapy is often prescribed for patients with cervical carcinoma after radiation therapy. A review of records of six teaching hospitals revealed 16 patients who had endometrial sampling for uterine bleeding after standard radiation therapy for cervical carcinoma. Fifteen patients underwent dilatation and curettage, and one patient underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy when a dilatation and curettage was unsuccessful. Six patients had fibrosis and inflammation of the endometrial cavity, seven had proliferative endometrium, one had cystic hyperplasia, one had atypical adenomatous hyperplasia, and one had adenocarcinoma. Although the number of patients who have an active endometrium after radiation therapy for cervical carcinoma is not known, this report demonstrates that proliferative endometrium may persist, and these patients may develop endometrial hyperplasia or adenocarcinoma. Studies have indicated that patients with normal endometrial glands have an increased risk of developing endometrial adenocarcinoma if they are treated with unopposed estrogen. Patients who have had radiation therapy for cervical carcinoma should be treated with estrogen and a progestational agent to avoid endometrial stimulation from unopposed estrogen therapy.

  8. Endometrial glands are required for preimplantation conceptus elongation and survival.

    PubMed

    Gray, C A; Taylor, K M; Ramsey, W S; Hill, J R; Bazer, F W; Bartol, F F; Spencer, T E

    2001-06-01

    Endometrial glands secrete molecules hypothesized to support conceptus growth and development. In sheep, endometrial gland morphogenesis occurs postnatally and can be epigenetically ablated by neonatal progestin exposure. The resulting stable adult uterine gland knockout (UGKO) phenotype was used here to test the hypothesis that endometrial glands are required for successful pregnancy. Mature UGKO ewes were bred repeatedly to fertile rams, but no pregnancies were detected by ultrasound on Day 25. Day 7 blastocysts from normal superovulated ewes were then transferred synchronously into Day 7 control or UGKO ewes. Ultrasonography on Days 25-65 postmating indicated that pregnancy was established in control, but not in UGKO ewes. To examine early uterine-embryo interactions, four control and eight UGKO ewes were bred to fertile rams. On Day 14, their uteri were flushed. The uterus of each control ewe contained two filamentous conceptuses of normal length. Uteri from four UGKO ewes contained no conceptus. Uteri of three UGKO ewes contained a single severely growth-retarded tubular conceptus, whereas the remaining ewe contained a single filamentous conceptus. Histological analyses of these uteri revealed that endometrial gland density was directly related to conceptus survival and developmental state. Day 14 UGKO uteri that were devoid of endometrial glands did not support normal conceptus development and contained either no conceptuses or growth-retarded tubular conceptuses. The Day 14 UGKO uterus with moderate gland development contained a filamentous conceptus. Collectively, these results demonstrate that endometrial glands and, by inference, their secretions are required for periimplantation conceptus survival and development.

  9. Hormone therapy for younger patients with endometrial cancer.

    PubMed

    Lee, Wen-Ling; Lee, Fa-Kung; Su, Wen-Hsiang; Tsui, Kuan-Hao; Kuo, Cheng-Deng; Hsieh, Shie-Liang Edmond; Wang, Peng-Hui

    2012-12-01

    The relationship between hormones and endometrial cancer is well known because disease states, such as chronic anovulation and endogenous estrogen production from hormone-secreting tumors (for example, granulosa cell tumor of the ovary), are related to excess estrogen, and unopposed estrogen use might lead to endometrial overgrowth, hyperplasia, and subsequent development of endometrial carcinoma. Therefore, the possibility of using antihormone therapy in endometrial carcinoma and/or its precancer lesions, such as simple hyperplasia with and without atypia and complex hyperplasia with and without atypia, is always supposed, as in the management of breast cancer. In addition, if women in whom endometrial cancer is diagnosed are very young, some critical issues should be considered, including the possibility of ovary preservation-partial preservation of fertility and the possibility of both ovary and uterus preservation-complete preservation of fertility. Other factors are also important to consider and include oncologic risk, appropriateness of candidates for treatment, type of hormone use, response rate of hormonal therapy, appropriate surveillance, and additional counseling for issues such as anxiety about relapse and metastasis, distress about side effects, advice of the family, advice of the medical staff, and economic burden. This review will be focused on updated information and recent knowledge of the use of hormones in the management of younger women with endometrial cancer who want fertility preservation.

  10. Adjuvant chemotherapy for endometrial cancer after hysterectomy

    PubMed Central

    Johnson, Nick; Bryant, Andrew; Miles, Tracie; Hogberg, Thomas; Cornes, Paul

    2014-01-01

    Background Endometrial adenocarcinoma (womb cancer) is a malignant growth of the lining (endometrium) of the womb (uterus). It is distinct from sarcomas (tumours of the uterine muscle). Survival depends the risk of microscopic metastases after surgery. Adjuvant (postoperative) chemotherapy improves survival from some other adenocarcinomas, and there is evidence that endometrial cancer is sensitive to cytotoxic therapy. This systematic review examines the effect of chemotherapy on survival after hysterectomy for endometrial cancer. Objectives To assess efficacy of adjuvant (postoperative) chemotherapy for endometrial cancer. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2010, Issue 3), MEDLINE and EMBASE up to August 2010, registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Selection criteria Randomised controlled trials (RCTs) comparing adjuvant chemotherapy with any other adjuvant treatment or no other treatment. Data collection and analysis We used a random-effects meta-analysis to assess hazard ratios (HR) for overall and progression-free survival and risk ratios (RR) to compare death rates and site of initial relapse. Main results Five RCTs compared no additional treatment with additional chemotherapy after hysterectomy and radiotherapy. Four trials compared platinum based combination chemotherapy directly with radiotherapy. Indiscriminate pooling of survival data from 2197 women shows a significant overall survival advantage from adjuvant chemotherapy (RR (95% CI) = 0.88 (0.79 to 0.99)). Sensitivity analysis focused on trials of modern platinum based chemotherapy regimens and found the relative risk of death to be 0.85 ((0.76 to 0.96); number needed to treat for an additional beneficial outcome (NNT) = 25; absolute risk reduction = 4% (1% to 8%)). The HR for overall survival is 0.74 (0.64 to 0.89), significantly

  11. Patient participation as dialogue: setting research agendas

    PubMed Central

    Abma, Tineke A.; Broerse, Jacqueline E. W.

    2010-01-01

    Abstract Background  Collaboration with patients in healthcare and medical research is an emerging development. We aimed to develop a methodology for health research agenda setting processes grounded in the notion of participation as dialogue. Methods  We conducted seven case studies between 2003 and 2007 to develop and validate a Dialogue Model for patient participation in health research agenda setting. The case studies related to spinal cord injury, neuromuscular diseases, renal failure, asthma/chronic obstructive pulmonary disease, burns, diabetes and intellectual disabilities. Results  The Dialogue Model is grounded in participatory and interactive approaches and has been adjusted on the basis of pilot work. It has six phases: exploration; consultation; prioritization; integration; programming; and implementation. These phases are discussed and illustrated with a case description of research agenda setting relating to burns. Conclusions  The dialogue model appeared relevant and feasible to structure the process of collaboration between stakeholders in several research agenda setting processes. The phase of consultation enables patients to develop their own voice and agenda, and prepares them for the broader collaboration with other stakeholder groups. Challenges include the stimulation of more permanent changes in research, and institutional transitions. PMID:20536537

  12. Dialogue or Exorcism? A Rejoinder to Schempp.

    ERIC Educational Resources Information Center

    Siedentop, Daryl

    1987-01-01

    When comparing research strategies in physical education, it serves no purpose to characterize the quantitative approach as contrived, unnatural, rigid, ahistorical, and simplistic while describing the qualitative approach as natural, responsive, context-relevant, flexible, and complex. What is needed is dialogue regarding similarities and…

  13. Engaging Men in Difficult Dialogues about Privilege

    ERIC Educational Resources Information Center

    Loschiavo, Chris; Miller, David S.; Davies, Jon

    2007-01-01

    Male privilege is one aspect of social inequality that underlies much of the oppression and violence that occurs on college campuses. Mad Skills, a program addressing power and privilege with college men, is described along with general recommendations about how to engage men in difficult dialogues. The PIE Model is used to describe defensive…

  14. Adaptive Dialogue Systems for Assistive Living Environments

    ERIC Educational Resources Information Center

    Papangelis, Alexandros

    2013-01-01

    Adaptive Dialogue Systems (ADS) are intelligent systems, able to interact with users via multiple modalities, such as speech, gestures, facial expressions and others. Such systems are able to make conversation with their users, usually on a specific, narrow topic. Assistive Living Environments are environments where the users are by definition not…

  15. Supporting Critical Dialogue across Educational Contexts

    ERIC Educational Resources Information Center

    Laman, Tasha Tropp; Jewett, Pamela; Jennings, Louise B.; Wilson, Jennifer L.; Souto-Manning, Mariana

    2012-01-01

    This article draws upon five different empirical studies to examine how critical dialogue can be fostered across educational settings and with diverse populations: middle-school students discussing immigration picture books, a teacher study group exploring texts on homelessness, a teacher education class studying critical literacy, working class…

  16. Unexpected Convergences: A Dialogue across Differences

    ERIC Educational Resources Information Center

    Ambrosio, John; Park, Gilbert C.

    2009-01-01

    Over the past two years, the authors have been meeting regularly to discuss issues and challenges related to multicultural education. The majority of their students are from small, rural, mostly White, working and middle class communities located within a 150 mile radius of the Midwestern campus where they teach. In this dialogue, the authors…

  17. Leadership for Social Justice: A Transnational Dialogue

    ERIC Educational Resources Information Center

    Blackmore, Jill

    2009-01-01

    This article is framed in two ways. First, by an editorial concern regarding the Americentricity of a special issue for the "Journal of Research on Educational Leadership" on leadership preparation. And second, Jean-Marie, Normore, and Brooks' (2009) desire for a "new social order" for a "multinational dialogue" as…

  18. Dialogue and Communication between School and Home.

    ERIC Educational Resources Information Center

    Bauch, Jerold P.

    This paper discusses school-home dialogue: its benefits; its theoretical underpinnings (Plato, Dewey, Hegel); perspectives on parent involvement, including societal changes that seem to produce barriers to communication between homes and schools (changes in family structure and role, time/schedule problems, distance, and educational bureaucracy);…

  19. Czech Basic Course: Air Force Dialogues.

    ERIC Educational Resources Information Center

    Defense Language Inst., Washington, DC.

    This is one of a series of supplementary materials used in the final phase of the "Czech Basic Course" developed and implemented at the Defense Language Institute. The purpose of this text is to acquaint students with specialized airport terminology pertaining to takeoff and landing precedures conducted in Czech. The dialogues, presented in…

  20. Peacebuilding Dialogue Pedagogies in Canadian Classrooms

    ERIC Educational Resources Information Center

    Bickmore, Kathy

    2014-01-01

    Constructively critical and inclusive dialogue about conflictual issues is one necessary ingredient of both democratic citizenship and peacebuilding learning. However, in North American classrooms populated by heterogeneous and non-affluent students, pedagogies involving discussion of conflicts are rarely fully implemented, sustained, or inclusive…

  1. Challenging Political Spectacle through Grassroots Policy Dialogues

    ERIC Educational Resources Information Center

    Winton, Sue; Evans, Michael P.

    2014-01-01

    Can simply talking about policy strengthen democracy? Drawing on data collected for case studies of one Canadian and two U.S. grassroots organizations, we demonstrate that taking part in policy dialogues hosted by grassroots organizations enables participants to gain greater clarity regarding policy issues, policy processes, and citizens'…

  2. Dialogue on Separation: Clinicians as Educators.

    ERIC Educational Resources Information Center

    Boss, Pauline Grossenbacher; Whitaker, Carl

    1979-01-01

    This dialogue on separation by three clinicians took place in a family relations class at the University of Wisconsin-Madison. It emphasizes the point that psychological separation, more than physical separation, is the essence of individuation, and that for students to understand the concept of individuation they must experience as well as study…

  3. Using Interactive Whiteboards to Orchestrate Classroom Dialogue

    ERIC Educational Resources Information Center

    Mercer, Neil; Hennessy, Sara; Warwick, Paul

    2010-01-01

    This paper focuses on the use of interactive whiteboards (IWBs) as a tool for encouraging and supporting classroom dialogue. The authors' concern here is with the promotion of "dialogic" communication between teachers and students, which is now widely recognised as educationally valuable. In this study they investigated how teachers…

  4. First Footing Inter-Faith Dialogue

    ERIC Educational Resources Information Center

    Luby, Antony

    2014-01-01

    This article examines an action research project on inter-faith dialogue within the sensitive context of Catholic pupils being taught Catholic religious education in state-funded secondary schools. Twenty pupils in S3 and S4 (Year 10 and Year 11) participated in a series of three paired conversations that focused primarily on science and religion,…

  5. Comparison of diagnostic accuracy between endometrial curettage and pipelle aspiration biopsy in patients treated with progestin for endometrial hyperplasia: a Korean Gynecologic Oncology Group Study (KGOG 2019).

    PubMed

    Kim, Mi Kyoung; Seong, Seok Ju; Lee, Taek Sang; Ki, Kyung-Do; Lim, Myong Cheol; Kim, Yun Hwan; Kim, Kidong; Joo, Won Duk

    2015-10-01

    A prospective multicenter trial has been started in Korea to evaluate the diagnostic accuracy of endometrial aspiration biopsy compared with dilatation and curettage in patients treated with progestin for endometrial hyperplasia. For conservative treatment of endometrial hyperplasia, orally administered progestins are most commonly used method with various treatment regimens and more recently, the levonorgestrel-releasing intrauterine system also has been used successfully to treat endometrial hyperplasia. However, there is no report about the accuracy of endometrial sampling during hormonal treatment for follow-up evaluation of endometrial hyperplasia. Patients with histologically confirmed endometrial hyperplasia are offered hormonal treatment with any one of the following three options: oral medroxyprogesterone acetate 10 mg/day for 14 days per cycle, continuous oral medroxyprogesterone acetate 10 mg/day or insertion of levonorgestrel-releasing intrauterine system. Histological surveillance is performed at 3 months or 6 months following initial treatment. Endometrial tissues are obtained via endometrial aspiration biopsy using a pipelle and dilatation and curettage. In the case of levonorgestrel-releasing intrauterine system, endometrial aspiration biopsy will be done with levonorgestrel-releasing intrauterine system in uterus and then, after the removal of levonorgestrel-releasing intrauterine system, dilatation and curettage will be done. The biopsy findings will be compared. The primary endpoint is to compare the pathological outcome of endometrial aspiration with dilatation and curettage. The secondary endpoint is the response rate with three types of progestin treatment at 6 months.

  6. Dialogue Education in the Post-Secondary Classroom: Reflecting on Dialogue Processes from Two Higher Education Settings in North America

    ERIC Educational Resources Information Center

    Gunnlaugson, Olen; Moore, Janet

    2009-01-01

    In this article, educators Olen Gunnlaugson and Janet Moore reflect on their experiences developing and facilitating two dialogue-based courses. They proceed with a brief overview of dialogue education and how they are situating their approaches to dialogue within the field of higher education and in terms of transformative learning. Each then…

  7. Uterine epithelial cell proliferation and endometrial hyperplasia: evidence from a mouse model.

    PubMed

    Gao, Yang; Li, Shu; Li, Qinglei

    2014-08-01

    In the uterus, epithelial cell proliferation changes during the estrous cycle and pregnancy. Uncontrolled epithelial cell proliferation results in implantation failure and/or cancer development. Transforming growth factor-β (TGF-β) signaling is a fundamental regulator of diverse biological processes and is indispensable for multiple reproductive functions. However, the in vivo role of TGF-β signaling in uterine epithelial cells remains poorly defined. We have shown that in the uterus, conditional deletion of the Type 1 receptor for TGF-β (Tgfbr1) using anti-Müllerian hormone receptor type 2 (Amhr2) Cre leads to myometrial defects. Here, we describe enhanced epithelial cell proliferation by immunostaining of Ki67 in the uteri of these mice. The aberration culminated in endometrial hyperplasia in aged females. To exclude the potential influence of ovarian steroid hormones, the proliferative status of uterine epithelial cells was assessed following ovariectomy. Increased uterine epithelial cell proliferation was also revealed in ovariectomized Tgfbr1 Amhr2-Cre conditional knockout mice. We further demonstrated that transcript levels for fibroblast growth factor 10 (Fgf10) were markedly up-regulated in Tgfbr1 Amhr2-Cre conditional knockout uteri. Consistently, treatment of primary uterine stromal cells with TGF-β1 significantly reduced Fgf10 mRNA expression. Thus, our findings suggest a potential involvement of TGFBR1-mediated signaling in the regulation of uterine epithelial cell proliferation, and provide genetic evidence supporting the role of uterine epithelial cell proliferation in the pathogenesis of endometrial hyperplasia.

  8. Ca2+ channel subunit α 1D promotes proliferation and migration of endometrial cancer cells mediated by 17β-estradiol via the G protein-coupled estrogen receptor.

    PubMed

    Hao, Juan; Bao, Xiaoxia; Jin, Bo; Wang, Xiujuan; Mao, Zebin; Li, Xiaoping; Wei, Lihui; Shen, Danhua; Wang, Jian-Liu

    2015-07-01

    Calcium and calcium channels are closely related to the estrogen-induced nongenomic effect of endometrial carcinoma, but the specific role of calcium channels is unknown. This study aimed to explore the expression and the biologic effect of the L-type calcium channel in endometrial carcinoma cells and to clarify the molecular mechanism of the relationship between L-type calcium channels and estrogen. The immunohistochemical results showed that Ca(2+) channel subunit α 1D (Cav1.3) expression was high in atypical hyperplasia (1.90 ± 0.35) and endometrial carcinoma tissues (2.05 ± 0.82) but weak (0.80 ± 0.15) in benign endometrial tissues (P < 0.05). Treatment with 17β-estradiol rapidly increased Cav1.3 expression in a dose- and time-dependent manner, and 100 nM cell-impermeable β-estradiol-6-(O-carboxymethyl)oxime:bovine serum albumin also promoted Cav1.3 expression. Transfection with small interfering RNA against G protein-coupled estrogen receptor (GPER) suppressed estrogen-induced up-regulation of Cav1.3 compared with control cells and markedly reduced the estrogen-induced phosphorylation of ERK1/2 and CREB. Knocking down the Cav1.3 significantly suppressed estrogen-stimulated Ca(2+) influx, cell proliferation, and migration in endometrial cancer cells. Taken together, Cav1.3 was overexpressed in atypical hyperplasia and endometrial carcinoma, and the estrogen-induced phosphorylation of downstream molecular ERK1/2 and CREB is the result of activation of the GPER pathway. L-type channel Cav1.3 is required for estrogen-stimulated Ca(2+) influx and contributes broadly to the development of endometrial cancer. The Cav1.3 channel may be a new target for endometrial carcinoma treatment.

  9. [Endometrial cancer in young patients: report of 17 cases].

    PubMed

    Dudnyikova, Anna; Horváth, Katalin; Pete, Imre

    2013-09-01

    Endometrial cancer of young (less then 40 years old) patients comprises 4-5% of all endometrial cancers in Hungary. The majority of patients did not give birth yet, so fertility sparing is very important. Fertility sparing treatment is possible if the tumor's histology is endometrial type and Grade 1 (well differentiated). The tumor localizes only to the endometrium and there is no myometrium infiltration. The authors present 17 cases of patients treated at the Department of Gynecology of National Institute of Oncology (Budapest, Hungary). In 3 cases conservative therapy (progesterone treatment) was possible, and 14 patients had to undergo surgery, because conservative treatment did fail. Of 17 patients 14 were never pregnant. The average patient's age was 32.35 ± 4.27 years. The mean body weight was 93.13 ± 30.79 kg (from 58 kg up to 147 kg); in 7 cases BMI (body mass index) was more than 30. After surgery histological examination had revealed 2 cases with normal ovaries, 1 case of simple cyst and 1 case of malignant ovarian tumor (serous adenocarcinoma, Grade 2), and 10 cases of polycystic ovaries associated with endometrial cancer. Of 3 cases that had only curettage, the endometrial cancer was Grade 1, and in 1 case radiological imaging showed simplex ovarian cyst. The authors' findings concerning young endometrial cancer patients confirm the results published in the literature. In cases suitable for fertility sparing treatment it is not sufficient to concentrate only on endometrial findings, but is very important to focus on the therapy of cystic ovaries (80% of which is PCO), obesity and diabetes mellitus as well.

  10. [The premalignant disease of the endometrium: endometrial intraepithelial neoplasia].

    PubMed

    Francz, Mónika

    2008-03-01

    The WHO 1994 classification for endometrial hyperplasias is based on the morphologic features of the lesions. This system characterizes the nuclear cytologic morphology as typical or atypical and describes the glandular architectural pattern as simple or complex. The main problem of this classification is the poor reproducibility. Although the predictive value of the atypical category is high, there are many typical hyperplasia cases with cancer progression. Modern molecular data related to endometrial tumorigenesis and precise computerized morphometric analysis have identified the lesion that may be considered as a precursor of endometrioid adenocarcinoma. By definition, this endometrial intraepithelial neoplasia (EIN) is a clonal proliferation of architecturally and cytologically altered endometrial glands which are prone to malignant transformation to endometrioid (type I) endometrial adenocarcinoma. The morphometric basis of EIN diagnosis is the D-score (DS), which is a logical combination of three morphometric features that represent the glandular complexity, glandular volume and cytological alterations. PTEN inactivation and K-ras mutation are the earliest genetic changes that can be revealed in these lesions. Hyperplasia cases that do not fit into the EIN categories are considered as benign or hormonal endometrial hyperplasia. This is the theoretical basis of a new classification system in premalignant endometrial diseases. Retrospective clinical data proved the high predictive value of the EIN scheme, so the decision on therapy can be more established. The reproducibility is excellent with application of precise definitions and PTEN immunohistochemistry. In the "Blue book" published in 2003 the WHO introduces the new morphometric- and molecular-based EIN system, and recommends it as an alternative classification method.

  11. Endometrial cancer with congenital uterine anomalies: three case reports and a literature review.

    PubMed

    Gao, Jinping; Zhang, Jintian; Tian, Wenyan; Teng, Fei; Zhang, Huiying; Zhang, Xuhong; Wang, Yingmei; Xue, Fengxia

    2017-01-24

    Background Uterine malformation is a rare deformity in woman, and only a few cases concerning endometrial cancer arising in patients with congenital uterine anomalies have been reported. Herein, we present three cases of endometrial cancer with different congenital uterine anomalies, and review studies involving congenital uterine anomalies associated with endometrial cancer in the past 25 years, in order to identify similarities and differences in clinicopathologic characteristics and prognosis between endometrial cancer associated with uterine anomalies, and normal uterus.

  12. Does Preoperative Diagnosis of Endometrial Hyperplasia Necessitate Intraoperative Frozen Section Consultation?

    PubMed Central

    Boyraz, Gokhan; Başaran, Derman; Salman, Mehmet C.; Özgül, Nejat; Yüce, Kunter

    2016-01-01

    Background In women with endometrial hyperplasia, there is a risk for co-existent endometrial cancer when patients are subjected to immediate surgical treatment. Aims The aim of this study was to investigate the frequency of endometrial cancer and the accuracy of frozen section analysis at the time of hysterectomy among patients with endometrial hyperplasia, to reveal whether or not a preoperative diagnosis of endometrial hyperplasia necessitates frozen section consultation. Study Design Retrospective cross-sectional study. Methods A department database review was performed to identify patients who were subjected to hysterectomy with a preoperative diagnosis of endometrial hyperplasia, during the period from 2007 to 2014. Results The study group included 189 cases. The final pathological examination revealed endometrial cancer in 16 women (8.4%). The risk of cancer in patients with endometrial hyperplasia was 1 of 125 (0.8%) in simple hyperplasia without atypia, 1 of 21 (4.8%) in complex hyperplasia without atypia and 14 of 43 (32.5%) in atypical hyperplasia. Of women with cancer, 2 of 16 (12.5%) had high-risk features. Frozen section analysis was requested in 46 cases. Frozen sections helped to identify six out of 11 cases of endometrial cancer (54.5%). The sensitivity, specificity and positive and negative predictive values of frozen section analysis for the detection of endometrial cancer among women with endometrial hyperplasia were 54.4%, 97.2%, 85.7% and 87.5%, respectively. Conclusion Although a significant proportion of patients with atypical endometrial hyperplasia are diagnosed with endometrial cancer following hysterectomy, most of these cases have low-risk features and do not require surgical staging. Additionally, intraoperative frozen section analysis if not helpful for diagnosing concurrent endometrial cancer in patients with endometrial hyperplasia. Therefore, it seems that patients with endometrial hyperplasia can be operated upon in settings with

  13. Loss of miR-542-3p enhances IGFBP-1 expression in decidualizing human endometrial stromal cells

    PubMed Central

    Tochigi, Hideno; Kajihara, Takeshi; Mizuno, Yosuke; Mizuno, Yumi; Tamaru, Shunsuke; Kamei, Yoshimasa; Okazaki, Yasushi; Brosens, Jan J; Ishihara, Osamu

    2017-01-01

    Endometrial decidualization represents an essential step for the successful implantation of the embryo; however, the molecular mechanism behind this differentiation process remains unclear. This study aimed to identify novel microRNAs (miRNAs) involved in the regulation of decidual gene expression in human endometrial stromal cells (HESCs). An in vitro analysis of primary undifferentiated and decidualizing HESCs was conducted. HESCs were isolated from hysterectomy specimens from normally cycling premenopausal women with uterine fibroids, who were not on hormonal treatment at the time of surgery. Primary HESCs were expanded in culture and decidualized with 8-bromo-cyclic adenosine monophosphate and medroxyprogesterone acetate. Microarray analysis identified six miRNAs differentially expressed in response to decidualization of HESCs. All but one miRNA were downregulated upon decidualization, including miR-542-3p. We demonstrated that miR-542-3p overexpression inhibits the induction of major decidual marker genes, including IGFBP1, WNT4 and PRL. In addition, miR-542-3p overexpression inhibited the morphological transformation of HESCs in response to deciduogenic cues. A luciferase reporter assay confirmed that the 3′-untranslated region of IGFBP1 mRNA is targeted by miR-542-3p. The results suggest that miR-542-3p plays an important role in endometrial decidualization by regulating the expression of major decidual marker genes. PMID:28051155

  14. Immunolocalization of Corticotropin-Releasing Hormone (CRH) and Its Receptors (CRHR1 and CRHR2) in Human Endometrial Carcinoma

    PubMed Central

    Sato, Naoko; Takagi, Kiyoshi; Suzuki, Takashi; Miki, Yasuhiro; Tanaka, Sota; Nagase, Satoru; Warita, Hitoshi; Fukudo, Shin; Sato, Fumiko; Sasano, Hironobu; Ito, Kiyoshi

    2014-01-01

    Objective Corticotropin-releasing hormone (CRH), a major regulator of the stress response, regulates various biological functions through its interaction with CRH receptors 1 (CRHR1) and 2 (CRHR2). CRH, CRHR1, and CRHR2 have recently been reported in several types of carcinoma, but the significance of these proteins has remained largely unknown in human endometrial carcinoma. Materials and Methods A total of 87 endometrial carcinoma specimens were obtained from Japanese female patients who underwent surgical treatment, fixed in 10% formalin, and embedded in paraffin wax. Immunohistochemistry for CRH, CRHR1, and CRHR2 was performed, and clinical data were obtained from the medical records. Results Immunopositivity of CRH, CRHR1, and CRHR2 in the specimens was 26%, 15%, and 10%, respectively. Univariate analysis revealed that immunohistochemical CRH status was positively associated with CRHR1 and CRHR2 status and that CRHR1 status was significantly associated with the risk of recurrence and poorer clinical outcome, whereas CRHR2 status was marginally associated with better prognosis for overall survival. Multivariate analysis demonstrated CRHR1 status as an independent prognostic factor for both disease-free and overall survival. Conclusions These results suggest that intratumoral CRH-CRHR1 signaling plays an important role in the progression of endometrial carcinoma and that CRHR1 is a potent prognostic factor in patients with this disease. PMID:25254562

  15. PME-1 modulates protein phosphatase 2A activity to promote the malignant phenotype of endometrial cancer cells.

    PubMed

    Wandzioch, Ewa; Pusey, Michelle; Werda, Amy; Bail, Sophie; Bhaskar, Aishwarya; Nestor, Mariya; Yang, Jing-Jing; Rice, Lyndi M

    2014-08-15

    Protein phosphatase 2A (PP2A) negatively regulates tumorigenic signaling pathways, in part, by supporting the function of tumor suppressors like p53. The PP2A methylesterase PME-1 limits the activity of PP2A by demethylating its catalytic subunit. Here, we report the finding that PME-1 overexpression correlates with increased cell proliferation and invasive phenotypes in endometrial adenocarcinoma cells, where it helps maintain activated ERK and Akt by inhibiting PP2A. We obtained evidence that PME-1 could bind and regulate protein phosphatase 4 (PP4), a tumor-promoting protein, but not the related protein phosphatase 6 (PP6). When the PP2A, PP4, or PP6 catalytic subunits were overexpressed, inhibiting PME-1 was sufficient to limit cell proliferation. In clinical specimens of endometrial adenocarcinoma, PME-1 levels were increased and we found that PME-1 overexpression was sufficient to drive tumor growth in a xenograft model of the disease. Our findings identify PME-1 as a modifier of malignant development and suggest its candidacy as a diagnostic marker and as a therapeutic target in endometrial cancer.

  16. Quantitative contrast-enhanced ultrasonography for the differential diagnosis of endometrial hyperplasia and endometrial neoplasms

    PubMed Central

    Liu, Ying; Xu, Yi; Cheng, Wen; Liu, Xinghan

    2016-01-01

    The present study aimed to investigate the feasibility of applying contrast-enhanced ultrasonography (CEUS) imaging technology for distinguishing between benign and malignant endometrial lesions, and to screen markers that could be correlated with the pathological results. In this study, endometrial diseases were diagnosed by biopsy under hysteroscopy and CEUS examinations. The intensity and time parameters of the time-intensity curve (TIC) were analyzed. The mean arrival time (AT), time-to-peak (TTP), rise time (RT), washout half-time and clearance half-time of malignant lesions were shorter than those of benign lesions (P<0.05), whereas the average peak intensity (PI) and enhancement intensity (EI) of malignant lesions were higher than those of benign lesions (P<0.05). The receiver operating characteristic curve showed the following cut-off values: PI, 29.2 dB; EI, 21.35 dB; AT, 12.75 sec; TTP, 26.75 sec; RT, 13.2 sec; clearance half-time, 89.3 sec; and washout half-time, 75.45 sec. The lesions with PI, an EI higher than that of the cut-off and lesions with an AT, TTP, RT, half clearing time and washout half-time shorter than the cut-off were considered malignant. The TTP, RT and half clearing time were negatively correlated with microvessel density (MVD), i.e., MVD was higher when the TTP, RT and half clearing time were shorter. Overall, changes in the enhancement and clearing of lesions could be quantitatively analyzed by CEUS TIC and further discriminate benign from malignant lesions. In the present study, CEUS appeared to indirectly reflect blood vessel changes inside the lesions and provided a pre-operative non-invasive fast imaging method for the diagnosis of endometrial disease. PMID:27895728

  17. Inhibition of Enhancer of Zeste Homolog 2 (EZH2) expression is associated with decreased tumor cell proliferation, migration and invasion in endometrial cancer cell lines

    PubMed Central

    Eskander, Ramez N.; Ji, Tao; Huynh, Be; Wardeh, Rooba; Randall, Leslie M; Hoang, Bang

    2013-01-01

    Objective To investigate the impact of Enhancer of Zeste Homolog 2 (EZH2) expression on endometrial cancer cell line behavior. Methods/materials EZH2 expression levels were compared between the non-malignant endometrial cell line T-HESC, and 3 endometrial cancer cell lines, ECC-1, RL95-2 and HEC1-A. Stable EZH2 knockdown cell lines were created and the impact on cellular proliferation, migration and invasion were determined. Fluorescent activated cell sorting was used to examine effects of EZH2 silencing on cell cycle progression. EZH2 expression in endometrial cancer tissue specimens was examined using immunohistochemistry. Comparison of differences between control and shEZH2 cell lines was performed using student's t test and Fischer's exact test. Results EZH2 protein expression was increased in all 3 cancer cell lines, and human endometrial cancer tissue specimens relative to control. RNA interference of EZH2 expression in ECC-1, RL95-2, and HEC1-A significantly decreased cell proliferation, migration and invasion. Down regulation of EZH2 expression resulted in a significant increase in the proportion of cells arrested in G2/M. RNA interference of EZH2 expression was associated with an increase in the expression of Wnt pathway inhibitors sFRP1 and DKK3, and a concomitant decrease in β-catenin. EZH2 expression in human tissue samples was significantly associated with increased stage, grade, depth of invasion and nodal metastasis. Conclusions EZH2 expression is associated with tumor cell proliferation, migration and invasion in 3 endometrial cancer cell lines, as well as increased stage, grade, depth of invasion and nodal metastasis in human cancer tissue specimens. Further investigation into this potential therapeutic target is warranted. PMID:23792601

  18. Cholesterol Synthetase DHCR24 Induced by Insulin Aggravates Cancer Invasion and Progesterone Resistance in Endometrial Carcinoma

    PubMed Central

    Dai, Miao; Zhu, Xiao-Lu; Liu, Fei; Xu, Qin-Yang; Ge, Qiu-Lin; Jiang, Shu-Heng; Yang, Xiao-Mei; Li, Jun; Wang, Ya-Hui; Wu, Qing-Kai; Ai, Zhi-Hong; Teng, Yin-Cheng; Zhang, Zhi-Gang

    2017-01-01

    3β-Hydroxysteroid-Δ24 reductase (DHCR24), the final enzyme of the cholesterol biosynthetic pathway, has been associated with urogenital neoplasms. However, the function of DHCR24 in endometrial cancer (EC) remains largely elusive. Here, we analyzed the expression profile of DHCR24 and the progesterone receptor (PGR) in our tissue microarray of EC (n = 258), the existing EC database in GEO (Gene Expression Omnibus), and TCGA (The Cancer Genome Atlas). We found that DHCR24 was significantly elevated in patients with EC, and that the up-regulation of DHCR24 was associated with advanced clinical stage, histological grading, vascular invasion, lymphatic metastasis, and reduced overall survival. In addition, DHCR24 expression could be induced by insulin though STAT3, which directly binds to the promoter elements of DHCR24, as demonstrated by ChIP-PCR and luciferase assays. Furthermore, genetically silencing DHCR24 inhibited the metastatic ability of endometrial cancer cells and up-regulated PGR expression, which made cells more sensitive to progestin. Taken together, we have demonstrated for the first time the crucial role of the insulin/STAT3/DHCR24/PGR axis in the progression of EC by modulating the metastasis and progesterone response, which could serve as potential therapeutic targets for the treatment of EC with progesterone receptor loss. PMID:28112250

  19. Beyond the brain-Peripheral kisspeptin signaling is essential for promoting endometrial gland development and function

    PubMed Central

    León, Silvia; Fernadois, Daniela; Sull, Alexandra; Sull, Judith; Calder, Michele; Hayashi, Kanako; Bhattacharya, Moshmi; Power, Stephen; Vilos, George A.; Vilos, Angelos G.; Tena-Sempere, Manuel; Babwah, Andy V.

    2016-01-01

    Uterine growth and endometrial gland formation (adenogenesis) and function, are essential for fertility and are controlled by estrogens and other regulators, whose nature and physiological relevance are yet to be elucidated. Kisspeptin, which signals via Kiss1r, is essential for fertility, primarily through its central control of the hypothalamic-pituitary-ovarian axis, but also likely through peripheral actions. Using genetically modified mice, we addressed the contributions of central and peripheral kisspeptin signaling in regulating uterine growth and adenogenesis. Global ablation of Kiss1 or Kiss1r dramatically suppressed uterine growth and almost fully prevented adenogenesis. However, while uterine growth was fully rescued by E2 treatment of Kiss1−/− mice and by genetic restoration of kisspeptin signaling in GnRH neurons in Kiss1r−/− mice, functional adenogenesis was only marginally restored. Thus, while uterine growth is largely dependent on ovarian E2-output via central kisspeptin signaling, peripheral kisspeptin signaling is indispensable for endometrial adenogenesis and function, essential aspects of reproductive competence. PMID:27364226

  20. Global transcriptomic profiling of bovine endometrial immune response in vitro. I. Effect of lipopolysaccharide on innate immunity.

    PubMed

    Oguejiofor, Chike F; Cheng, Zhangrui; Abudureyimu, Ayimuguli; Fouladi-Nashta, Ali A; Wathes, D Claire

    2015-10-01

    The dysregulation of endometrial immune response to bacterial lipopolysaccharide (LPS) has been implicated in uterine disease and infertility in the postpartum dairy cow, although the mechanisms are not clear. Here, we investigated whole-transcriptomic gene expression in primary cultures of mixed bovine epithelial and stromal endometrial cells. Cultures were exposed to LPS for 6 h, and cellular response was measured by bovine microarray. Approximately 30% of the 1006 genes altered by LPS were classified as being involved in immune response. Cytokines and chemokines (IL1A, CX3CL1, CXCL2, and CCL5), interferon (IFN)-stimulated genes (RSAD2, MX2, OAS1, ISG15, and BST2), and the acute phase molecule SAA3 were the most up-regulated genes. Ingenuity Pathway Analysis identified up-regulation of many inflammatory cytokines and chemokines, which function to attract immune cells to the endometrium, together with vascular adhesion molecules and matrix metalloproteinases, which can facilitate immune cell migration from the tissue toward the uterine lumen. Increased expression of many IFN-signaling genes, immunoproteasomes, guanylate-binding proteins, and genes involved in the intracellular recognition of pathogens suggests important roles for these molecules in the innate defense against bacterial infections. Our findings confirmed the important role of endometrial cells in uterine innate immunity, whereas the global approach used identified several novel immune response pathways triggered by LPS in the endometrium. Additionally, many genes involved in endometrial response to the conceptus in early pregnancy were also altered by LPS, suggesting one mechanism whereby an ongoing response to infection may interfere with the establishment of pregnancy.

  1. Body Mass Index Genetic Risk Score and Endometrial Cancer Risk

    PubMed Central

    Prescott, Jennifer; Setiawan, Veronica W.; Wentzensen, Nicolas; Schumacher, Fredrick; Yu, Herbert; Delahanty, Ryan; Bernstein, Leslie; Chanock, Stephen J.; Chen, Chu; Cook, Linda S.; Friedenreich, Christine; Garcia-Closas, Monserrat; Haiman, Christopher A.; Le Marchand, Loic; Liang, Xiaolin; Lissowska, Jolanta; Lu, Lingeng; Magliocco, Anthony M.; Olson, Sara H.; Risch, Harvey A.; Shu, Xiao-Ou; Ursin, Giske; Yang, Hannah P.; Kraft, Peter; De Vivo, Immaculata

    2015-01-01

    Genome-wide association studies (GWAS) have identified common variants that predispose individuals to a higher body mass index (BMI), an independent risk factor for endometrial cancer. Composite genotype risk scores (GRS) based on the joint effect of published BMI risk loci were used to explore whether endometrial cancer shares a genetic background with obesity. Genotype and risk factor data were available on 3,376 endometrial cancer case and 3,867 control participants of European ancestry from the Epidemiology of Endometrial Cancer Consortium GWAS. A BMI GRS was calculated by summing the number of BMI risk alleles at 97 independent loci. For exploratory analyses, additional GRSs were based on subsets of risk loci within putative etiologic BMI pathways. The BMI GRS was statistically significantly associated with endometrial cancer risk (P = 0.002). For every 10 BMI risk alleles a woman had a 13% increased endometrial cancer risk (95% CI: 4%, 22%). However, after adjusting for BMI, the BMI GRS was no longer associated with risk (per 10 BMI risk alleles OR = 0.99, 95% CI: 0.91, 1.07; P = 0.78). Heterogeneity by BMI did not reach statistical significance (P = 0.06), and no effect modification was noted by age, GWAS Stage, study design or between studies (P≥0.58). In exploratory analyses, the GRS defined by variants at loci containing monogenic obesity syndrome genes was associated with reduced endometrial cancer risk independent of BMI (per BMI risk allele OR = 0.92, 95% CI: 0.88, 0.96; P = 2.1 x 10−5). Possessing a large number of BMI risk alleles does not increase endometrial cancer risk above that conferred by excess body weight among women of European descent. Thus, the GRS based on all current established BMI loci does not provide added value independent of BMI. Future studies are required to validate the unexpected observed relation between monogenic obesity syndrome genetic variants and endometrial cancer risk. PMID:26606540

  2. The palaeontological exhibition: a venue for dialogue.

    PubMed

    Murriello, Sandra

    2015-01-01

    Understanding the dialogue between museums and their visitors enables museums to subsist, undergo transformations and become consolidated as socially valued cultural venues. The Museo de La Plata (Argentina) was created in the late nineteenth century as a natural history museum, and this study shows that currently the museum is valued socially as a venue for family leisure and education, at which people make sense to the objects exhibited through characteristics conferred upon them by both the institution and the visitor. Nevertheless, such dialogue is somehow affected by the museographic proposal and the public interpretation of the institutional narrative, which could be analysed within the frame of contextual learning. As a consequence, the evolutionary idea that the museum aims to communicate is distorted by the public. This article highlights the importance of considering the visitors' interpretations when planning museum exhibitions, a perspective that has been rather absent in the Argentinian museums.

  3. Asymmetric quantum dialogue in noisy environment

    NASA Astrophysics Data System (ADS)

    Banerjee, Anindita; Shukla, Chitra; Thapliyal, Kishore; Pathak, Anirban; Panigrahi, Prasanta K.

    2017-02-01

    A notion of asymmetric quantum dialogue (AQD) is introduced. Conventional protocols of quantum dialogue are essentially symmetric as the users (Alice and Bob) can encode the same amount of classical information. In contrast, the proposed scheme for AQD provides different amount of communication powers to Alice and Bob. The proposed scheme offers an architecture, where the entangled state to be used and the encoding scheme to be shared between Alice and Bob depend on the amount of classical information they want to exchange with each other. The general structure for the AQD scheme has been obtained using a group theoretic structure of the operators introduced in Shukla et al. (Phys Lett A 377:518, 2013). The effect of different types of noises (e.g., amplitude damping and phase damping noise) on the proposed scheme is investigated, and it is shown that the proposed scheme for AQD is robust and it uses an optimized amount of quantum resources.

  4. The significance of markers in the diagnosis of endometrial cancer

    PubMed Central

    Żyła, Monika M.; Wilczyński, Jacek R.; Kostrzewa, Marta; Księżakowska-Łakoma, Kinga; Nowak, Marek; Stachowiak, Grzegorz; Szyłło, Krzysztof

    2016-01-01

    Endometrial cancer is one of the most common cancers experienced by women throughout the world. It is also the most common malignancy within the female reproductive system, representing 37.7% of all disorders. The incidence increases with age, and is diagnosed most frequently in women between 45 and 65 years old. In the last few years, numerous studies have been performed to identify tumour biomarkers. Biomarkers include not only protein routinely used as tumour markers but also genes and chromosomes. The limiting factor in the use of markers in the diagnosis of endometrial cancer is their lack of specificity. However, specific markers for endometrial cancer are the subject of much research attention. Although moderately elevated levels of markers are present in a number of inflammatory or non-malignant diseases, significantly increased levels of markers indicate the development of cancer. Recently, research has been focused on the identification of molecular changes leading to different histological subtypes of endometrial cancer. In this paper the authors reviewed several currently investigated markers. Progress in these investigations is very important in the diagnostics and treatment of endometrial cancer. In particular, the identification of novel mutations and molecular profiles should enhance our ability to personalise adjuvant treatment with genome-guided targeted therapy. PMID:27980530

  5. Endometrial bleeding in postmenopausal women: with and without hormone therapy.

    PubMed

    Archer, David F

    2011-04-01

    The aim of this study was to present a review of the potential mechanisms involved in the occurrence of endometrial bleeding in postmenopausal women using hormone therapy. Selected literature on the incidence of bleeding in postmenopausal women using estrogen progestogen therapy was reviewed. The incidence of spotting and bleeding in women using continuous-combined hormone therapy was presented. Relevant articles related to the role of angiogenic factors and vasculogenesis in the endometrium, endometrial leukocytes, and endometrial metalloproteinases were used for the review. The cause or etiology of endometrial bleeding with hormone therapy is unknown. Several options are known to alter angiogenesis or be involved in tissue remodeling during normal menstruation. Vascular endothelial growth factor and thrombospondin-1 are proangiogenic and antiangiogenic factors that could cause dysfunction in vasculogenesis that could result in blood vessel fragility and bleeding. The role of pericytes in maintaining vessel morphology and integrity is discussed. Endometrial leukocytes and metalloproteinases are involved in normal menstruation, but their role in postmenopausal bleeding is not clear suggesting involvement of mechanisms in the bleeding. There is limited information on clinical investigation into the etiology of postmenopausal bleeding associated with hormone therapy. The major cause of hormone therapy-related bleeding is unknown. Alterations in angiogenic factors that could result in vascular dysfunction and vessel breakdown provide a working hypothesis as to the potential cause of vessel breakdown.

  6. Cervical cytology in serous and endometrioid endometrial cancer.

    PubMed

    Roelofsen, Thijs; Geels, Yvette P; Pijnenborg, Johanna M A; van Ham, Maaike A P C; Zomer, Saskia F; van Tilburg, Johanna M Wiersma; Snijders, Marc P M L; Siebers, Albert G; Bulten, Johan; Massuger, Leon F A G

    2013-07-01

    The aim of this study was to determine the frequency of abnormal cervical cytology in preoperative cervical cytology of patients diagnosed with uterine papillary serous carcinoma (UPSC) and endometrioid endometrial carcinoma (EEC). In addition, associations between abnormal cervical cytology and clinicopathologic factors were evaluated. In this multicentre study, EEC patients diagnosed at two hospitals from 1999 to 2009 and UPSC patients diagnosed at five hospitals from 1992 to 2009, were included. Revision of the histologic slides was performed systematically and independently by 3 gynecopathologists. Cervical cytology within six months before histopathologic diagnosis of endometrial carcinoma was available for 267 EEC and 80 UPSC patients. Cervical cytology with atypical, malignant, or normal endometrial cells in postmenopausal women was considered as abnormal cytology, specific for endometrial pathology. Abnormal cervical cytology was found in 87.5% of UPSC patients, compared with 37.8% in EEC patients. In UPSC, abnormal cytology was associated with extrauterine spread of disease (P=0.043). In EEC, abnormal cytology was associated with cervical involvement (P=0.034). In both EEC and UPSC patients, abnormal cervical cytology was not associated with survival. In conclusion, abnormal cervical cytology was more frequently found in UPSC patients. It was associated with extrauterine disease in UPSC patients, and with cervical involvement in EEC patients. More prospective research should be performed to assess the true clinical value of preoperative cervical cytology in endometrial cancer patients.

  7. Controlled quantum dialogue robust against conspiring users

    NASA Astrophysics Data System (ADS)

    Kao, Shih-Hung; Hwang, Tzonelih

    2016-10-01

    This paper explores a new security problem in controlled quantum dialogue (CQD) protocols, where the communicants may try to conspire to communicate without the controller's permission. According to our survey, all the previous CQD protocols suffer from this attack. In order to resolve this problem, we also present an improvement protocol. The security analyses show that the improved scheme is secure under this and other well-known attacks.

  8. Efficient quantum dialogue without information leakage

    NASA Astrophysics Data System (ADS)

    Yin, Ai-Han; Tang, Zhi-Hui; Chen, Dong

    2015-02-01

    A two-step quantum dialogue scheme is put forward with a class of three-qubit W state and quantum dense coding. Each W state can carry three bits of secret information and the measurement result is encrypted without information leakage. Furthermore, we utilize the entangle properties of W state and decoy photon checking technique to realize three-time channel detection, which can improve the efficiency and security of the scheme.

  9. Aquaporin 5 Plays a Role in Estrogen-Induced Ectopic Implantation of Endometrial Stromal Cells in Endometriosis.

    PubMed

    Jiang, Xiu Xiu; Fei, Xiang Wei; Zhao, Li; Ye, Xiao Lei; Xin, Liao Bin; Qu, Yang; Xu, Kai Hong; Wu, Rui Jin; Lin, Jun

    2015-01-01

    Aquaporin 5 (AQP5) participates in the migration of endometrial cells. Elucidation of the molecular mechanisms associated with AQP5-mediated, migration of endometrial cells may contribute to a better understanding of endometriosis. Our objectives included identifying the estrogen-response element (ERE) in the promoter region of the AQP5 gene, and, investigating the effects of AQP5 on ectopic implantation of endometrial cells. Luciferase reporter assays and electrophoretic mobility shift assay (EMSA) identified the ERE-like motif in the promoter region of the AQP5 gene. After blocking and up-regulating estradiol (E2) levels, we analysed the expression of AQP5 in endometrial stromal (ES) cells. After blocking E2 /or phosphatidylinositol 3 kinase(PI3K), we analysed the role of AQP5 in signaling pathways. We constructed an AQP5, shRNA, lentiviral vector to knock out the AQP5 gene in ES cells. After knock-out of the AQP5 gene, we studied the role of AQP5 in cell invasion, proliferation, and the formation of ectopic endometrial implants in female mice. We identified an estrogen-response element in the promoter region of the AQP5 gene. Estradiol (E2) increased AQP5 expression in a dose-dependent fashion, that was blocked by ICI182,780(an estrogen receptor inhibitor). E2 activated PI3K /protein kinase B(AKT) pathway (PI3K/AKT), that, in turn, increased AQP5 expression. LY294002(PI3K inhibitor) attenuated estrogen-enhanced, AQP5 expression. Knock-out of the AQP5 gene with AQP5 shRNA lentiviral vector significantly inhibited E2-enhanced invasion, proliferation of ES cells and formation of ectopic implants. Estrogen induces AQP5 expression by activating ERE in the promoter region of the AQP5gene, activates the PI3K/AKT pathway, and, promotes endometrial cell invasion and proliferation. These results provide new insights into some of the mechanisms that may underpin the development of deposits of ectopic endometrium.

  10. Control of human endometrial stromal cell motility by PDGF-BB, HB-EGF and trophoblast-secreted factors.

    PubMed

    Schwenke, Maren; Knöfler, Martin; Velicky, Philipp; Weimar, Charlotte H E; Kruse, Michelle; Samalecos, Annemarie; Wolf, Anja; Macklon, Nick S; Bamberger, Ana-Maria; Gellersen, Birgit

    2013-01-01

    Human implantation involves extensive tissue remodeling at the fetal-maternal interface. It is becoming increasingly evident that not only trophoblast, but also decidualizing endometrial stromal cells are inherently motile and invasive, and likely contribute to the highly dynamic processes at the implantation site. The present study was undertaken to further characterize the mechanisms involved in the regulation of endometrial stromal cell motility and to identify trophoblast-derived factors that modulate migration. Among local growth factors known to be present at the time of implantation, heparin-binding epidermal growth factor-like growth factor (HB-EGF) triggered chemotaxis (directed locomotion), whereas platelet-derived growth factor (PDGF)-BB elicited both chemotaxis and chemokinesis (non-directed locomotion) of endometrial stromal cells. Supernatants of the trophoblast cell line AC-1M88 and of first trimester villous explant cultures stimulated chemotaxis but not chemokinesis. Proteome profiling for cytokines and angiogenesis factors revealed neither PDGF-BB nor HB-EGF in conditioned media from trophoblast cells or villous explants, while placental growth factor, vascular endothelial growth factor and PDGF-AA were identified as prominent secretory products. Among these, only PDGF-AA triggered endometrial stromal cell chemotaxis. Neutralization of PDGF-AA in trophoblast conditioned media, however, did not diminish chemoattractant activity, suggesting the presence of additional trophoblast-derived chemotactic factors. Pathway inhibitor studies revealed ERK1/2, PI3 kinase/Akt and p38 signaling as relevant for chemotactic motility, whereas chemokinesis depended primarily on PI3 kinase/Akt activation. Both chemotaxis and chemokinesis were stimulated upon inhibition of Rho-associated, coiled-coil containing protein kinase. The chemotactic response to trophoblast secretions was not blunted by inhibition of isolated signaling cascades, indicating activation of

  11. Paclitaxel and Carboplatin With or Without Metformin Hydrochloride in Treating Patients With Stage III, IV, or Recurrent Endometrial Cancer

    ClinicalTrials.gov

    2017-02-23

    Endometrial Adenocarcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Serous Adenocarcinoma; Endometrial Undifferentiated Carcinoma; 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

  12. Association of the Apolipoprotein E 2 Allele with Concurrent Occurrence of Endometrial Hyperplasia and Endometrial Carcinoma

    PubMed Central

    Ivanova, Tatiana I.; Krikunova, Ludmila I.; Ryabchenko, Nikolay I.; Mkrtchyan, Liana S.; Khorokhorina, Vera A.; Salnikova, Lyubov E.

    2015-01-01

    Genes encoding proteins with antioxidant properties may influence susceptibility to endometrial hyperplasia (EH) and endometrial carcinoma (ECa). Patients with EH (n = 89), EH concurrent with ECa (n = 76), ECa (n = 186), and healthy controls (n = 1110) were genotyped for five polymorphic variants in the genes involved in metabolism of lipoproteins (APOE Cys112Arg and Arg158Cys), iron (HFE Cys282Tyr and His63Asp), and catecholamines (COMT Val158Met). Patients and controls were matched by ethnicity (all Caucasians), age, body mass index (BMI), and incidence of hypertension and diabetes. The frequency of the APOE E 2 allele (158Cys) was higher in patients with EH + ECa than in controls (P = 0.0012, PBonferroni = 0.018, OR = 2.58, 95% CI 1.49–4.45). The APOE E 4 allele (112Arg) was more frequently found in patients with EH than in controls and HFE minor allele G (63Asp) had a protective effect in the ECa group, though these results appeared to be nonsignificant after correction for multiple comparisons. The results of the study indicate that E 2 allele might be associated with concurrent occurrence of EH and ECa. PMID:25741405

  13. Suppressed expression of insulin-like growth factor binding protein-1 mRNA in the endometrium: a molecular mechanism associating endometrial cancer with its risk factors.

    PubMed

    Rutanen, E M; Nyman, T; Lehtovirta, P; Ammälä, M; Pekonen, F

    1994-11-01

    The insulin-like growth factor (IGF) system is thought to function as a mediator of steroid hormone actions in the endometrium. IGFs (IGF-I and IGF-II) are also potent mitogens in endometrial cancer. The biological actions of IGFs are modulated by specific binding proteins (IGFBP)--6 cloned and sequenced so far--which may either inhibit or enhance the effects of IGF at the cellular level. In the endometrium, IGFBP-1 gene expression is stimulated by progesterone and inhibited by insulin, while IGFBP-1 inhibits the mitogenic action of IGF-I. In this study, we used a quantitative reverse transcriptase polymerase chain reaction (RT-PCR) to investigate IGFBP-1, IGFBP-2, IGFBP-4, IGFBP-5 and IGFBP-6 gene expression in endometrial cancer tissues. Endometrial cancer tissue samples were collected from 20 women (aged 54-79 yrs) with stage I to II well-differentiated endometrial adenocarcinoma. Samples of normal endometrium (n = 14) obtained from women undergoing tubal ligation in various phases of the menstrual cycle, and normal early-pregnancy endometrium (decidua) were studied for comparison. In endometrial cancer tissues, the IGFBP-1 mRNA was undetectable or minimally expressed when studied by RT-PCR. The mean (+ SD) levels of IGFBP-2 and IGFBP-4 and IGFBP-5 mRNAs in endometrial cancer tissues did not differ from those in normal endometrium, in which no cyclic variation was observed, suggesting that the genes encoding IGFBP-2, IGFBP-4 and IGFBP-5 are not hormonally regulated in the endometrium. The IGFBP-6 mRNA expression showed a significant cyclic variation in normal endometrium, with low levels in late-proliferative and early- to mid-secretory phases and high expression in late-secretory and early-proliferative phases. In endometrial cancer tissues, the mean IGFBP-6 mRNA level was similar to that in cycling endometrium during the peri-ovulatory period. In summary, a continuous stimulation of the endometrial epithelial cells by IGFs with suppressed IGFBP-1 expression

  14. Colony-stimulating factor-1 and c-fms expression in human endometrial tissues and placenta during the menstrual cycle and early pregnancy.

    PubMed

    Kauma, S W; Aukerman, S L; Eierman, D; Turner, T

    1991-10-01

    Colony-stimulating factor-1 (CSF-1), a growth factor produced by monocytes, macrophages, fibroblasts, and endothelial cells, has been implicated in the functional regulation and growth of the murine placenta through the presence of the CSF-1 receptor, c-fms, found in this tissue. In this study we examined the tissue levels of CSF-1 by RIA and the relative expression of CSF-1 and c-fms mRNA by Northern blot analysis in human endometrial, decidual, and placental tissues during the normal menstrual cycle and early pregnancy. All endometrial, decidual, and placental tissues demonstrated extractable immunoreactive CSF-1 and expressed the 4.0-kilobase CSF-1 mRNA species. First trimester decidual tissue expressed higher levels of CSF-1 mRNA than proliferative (3.2-fold higher; P less than 0.01) or secretory (2.4-fold higher; P less than 0.01) endometrial tissues, whereas proliferative and secretory endometrial tissues expressed similar levels of CSF-1 mRNA. Tissue extractable levels of immunoreactive CSF-1 were 3.2-fold (P less than 0.05) higher in first trimester decidual tissue and 2.9-fold (P less than 0.05) higher in secretory endometrial tissue compared to levels in proliferative endometrial tissue, whereas first trimester decidua and secretory endometrial tissues had similar levels of immunoreactive CSF-1. There was expression of c-fms mRNA in all endometrial and first trimester decidual tissue samples, with little change during the menstrual cycle and early pregnancy. In placenta, there was a positive correlation of increasing CSF-1 and c-fms mRNA expression with increasing gestational age. These results suggest that there is increased local production of CSF-1 in tissues found at the maternal-fetal interface during the time of implantation and early pregnancy. This increased production of CSF-1 may play a role in decidual function and placental growth through the presence of c-fms in these tissues.

  15. Contradictions and dialectics in the palliative dialogue: enhancing the palliative dialogue by dialectical principles.

    PubMed

    Samson, Tali; Shvartzman, Pesach

    2014-11-01

    The application of required communication skills in the palliative dialogue necessitates a significant transition from the paternalistic medical approach to the holistic psychosocial approach that focuses on the patient and views the individual as a whole entity. Understanding the evolution of a therapeutic relationship in terms of entrance into the relationship, development, maintenance, and leave taking as well as the adoption of dialectical ideas gives palliative caregivers flexibility in the dialogue with patients and families. Accepting the principles of dialectics, in which the existence of contradictions is seen as an inherent part of a reality that is undergoing constant change, gives the caregiver the flexibility to interpret dichotomic thoughts and emotions as a dialectic failure and, in accordance, to move toward a synthesis of the ideas of living and dying. This approach provides caregivers the means to promote the palliative dialogue, implement varied communication skills to clarify the patient's goals, and implement a therapeutic plan to realize them.

  16. Role of epigenomics in ovarian and endometrial cancers.

    PubMed

    Balch, Curtis; Matei, Daniela E; Huang, Tim H-M; Nephew, Kenneth P

    2010-06-01

    Ovarian cancer is the most lethal gynecologic malignancy and while constituting only 3% of all female cancers, it causes 14,600 deaths in the USA annually. Endometrial cancer, the most diagnosed and second-most fatal gynecologic cancer, afflicts over 40,000 US women annually, causing an estimated 7780 deaths in 2009. In both advanced ovarian and endometrial carcinomas, the majority of initially therapy-responsive tumors eventually evolve to a fully drug-resistant phenotype. In addition to genetic mutations, epigenetic anomalies are frequent in both gynecologic malignancies, including aberrant DNA methylation, atypical histone modifications and dysregulated expression of distinct microRNAs, resulting in altered gene-expression patterns favoring cell survival. In this article, we summarize the most recent hypotheses regarding the role of epigenetics in ovarian and endometrial cancers, including a possible role in tumor 'stemness' and also evaluate the possible therapeutic benefits of reversal of these oncogenic chromatin aberrations.

  17. IMP2 expression distinguishes endometrioid from serous endometrial adenocarcinomas.

    PubMed

    Zhang, Liping; Liu, Yuxin; Hao, Suyang; Woda, Bruce A; Lu, Di

    2011-06-01

    Among various endometrial adenocarcinomas, endometrioid carcinoma can be very difficult to separate from serous carcinomas. Various biomarkers have been studied with proven value, including p53, Ki-67, and p16. In this study, we present data on another biomarker, IMP2, which we believe is sensitive and specific. Using 320 endometrial biopsy cases, we demonstrate that IMP2 is normally expressed in all proliferative and inactive endometrial glandular cells. The pattern of such expression is unchanged in serous carcinomas. IMP2 expression is, however, lost in all cases of endometrioid carcinomas by at least 25% to >95% of tumor cell populations. Therefore, loss of IMP2 expression can differentiate endometrioid from serous carcinomas. Such finding of IMP2 expression remained the same in mixed endometrioid and serous carcinomas; IMP2 expression is lost in all endometrioid components by at least 25% of tumor cell population, whereas it remained diffuse and strong in all serous components of carcinomas.

  18. Pathophysiology and management of endometrial hyperplasia and carcinoma.

    PubMed Central

    Fu, Y. S.; Gambone, J. C.; Berek, J. S.

    1990-01-01

    Endometrial cancer is currently the commonest pelvic malignancy affecting American women, most of whom share the same pathophysiologic basis, that is, unopposed estrogenic stimulation. The initial result of hyperestrogenism is the development of endometrial hyperplasia, which is reversible in most cases by appropriate hormonal therapy. Persistent stimulation eventually leads to atypical hyperplasia with nuclear atypia and invasive carcinoma. Because there is no cost-effective screening method for the detection of endometrial hyperplasia and carcinoma, it is essential to survey the high-risk population with appropriate diagnostic techniques. After diagnosis, therapy should be individualized based on pathologic findings (cell type and histologic grade) and extent of disease (International Federation of Gynaecologists and Obstetricians stage, depth of myometrial invasion, and pelvic and para-aortic lymph node status). Recent studies suggest that sex hormone receptors and nuclear DNA ploidy patterns provide useful prognostic information independent of histologic grade. Images PMID:2202159

  19. Laparoscopic Assisted Surgical Staging (LASS) for Endometrial Cancer

    PubMed

    Vidal; Garza-Leal; Iglesias; Salvidar; Garza

    1994-08-01

    We report the first four cases of LASS for endometrial cancer in Mexico. Four patients diagnosed with endometrial adenocarcinoma were selected. These patients underwent peritoneal washing, vaginally assisted laparoscopic hysterectomy, bilateral salpingo-oophorectomy and pelvic biopsies. These biopsies included dissection of common iliac vessel, hypogastric and external vessels, and obturator nerve. An average of 10 nodes were obtained (8-11). In all patients both the nodes and the peritoneal washings were negative. The pathologic surgical staging was: three patients with IBG2 and one patient with IAG2. The patients were discharged on the sixth postoperative day, without complications. The follow-up is of 1 to 7 months and all are alive and without tumor activity. Patients with endometrial cancer often have associated obesity, diabetes and hypertension. For this reason the practice of minimally invasive surgery reduces morbidity. However, a full knowledge of anatomy, oncologic gynecology, and operative laparoscopy is imperative.

  20. ESMO-ESGO-ESTRO Consensus Conference on Endometrial Cancer

    PubMed Central

    Colombo, Nicoletta; Creutzberg, Carien; Amant, Frederic; Bosse, Tjalling; González-Martín, Antonio; Ledermann, Jonathan; Marth, Christian; Nout, Remi; Querleu, Denis; Mirza, Mansoor Raza; Sessa, Cristiana

    2016-01-01

    Abstract The first joint European Society for Medical Oncology (ESMO), European SocieTy for Radiotherapy & Oncology (ESTRO) and European Society of Gynaecological Oncology (ESGO) consensus conference on endometrial cancer was held on 11–13 December 2014 in Milan, Italy, and comprised a multidisciplinary panel of 40 leading experts in the management of endometrial cancer. Before the conference, the expert panel prepared three clinically-relevant questions about endometrial cancer relating to the following four areas: prevention and screening, surgery, adjuvant treatment and advanced and recurrent disease. All relevant scientific literature, as identified by the experts, was reviewed in advance. During the consensus conference, the panel developed recommendations for each specific question and a consensus was reached. Results of this consensus conference, together with a summary of evidence supporting each recommendation, are detailed in this article. All participants have approved this final article. PMID:26645990

  1. New endometrial ablation techniques for treatment of menorrhagia.

    PubMed

    Bradley, Linda D

    2004-01-01

    Endometrial ablation is an excellent alternative to hysterectomy in women with menorrhagia and small intramural fibroids. Preoperative evaluation, which includes office hysteroscopy or saline infusion sonography, is critical to patient management and choice of procedure. A vast array of endometrial ablation technology is available currently that includes balloon therapy, cryosurgery hot circulating saline, bipolar impedance technology, and microwave: (1) ThermaChoice UTB System (Gynecare, Inc., Somerville, NJ, USA), (2) Uterine Balloon Therapy (UBT) System, HerOption Uterine Cryoblation Therapy System (American Medical Systems, Inc., Minnetonka, MN, USA), (3) Hydro ThermAblator HTA System (BEI Medical/Boston Scientific, Natick, MA), (4) NovaSure System (Novacept, Palo Alto, CA, USA), and (5) Microsulis Microwave Endometrial Ablation (MEA) System (Microsulis Medical Ltd., Pompano Beach, FL, USA). Each method is described herein, and Summary of Safety and Effectiveness Data (SSED) data for each product are reviewed.

  2. Endometrial cancer implanted within a cesarean section scar.

    PubMed

    Baba, Tsukasa; Mandai, Masaki; Yamanishi, Yukio; Suzuki, Ayako; Kang, Hyun Sook; Konishi, Ikuo

    2011-03-01

    Several reports have documented adenocarcinoma arising from endometriotic implants within cesarean section (C-S) scars on the serosal surface of the uterus; however, endometrial cancer invading the C-S scar from the uterine cavity has not been described. We report a case of a grade 1 endometrioid adenocarcinoma 'drop' lesion invading a previous C-S scar with resultant cervical stromal invasion. Using both MR images and a thorough review of the pathology, the tumor at the C-S scar was determined to be an implant derived from a primary lesion at the uterine fundus. With increases in the incidence of both endometrial cancer and births by C-S, it is likely we will encounter more cases of iatrogenic implants of endometrial cancers in C-S scars.

  3. Tubal Pregnancy Associated with Endometrial Carcinoma after In Vitro Fertilization Attempts

    PubMed Central

    Bayoglu Tekin, Yesim; Guvendag Guven, Emine Seda; Sehitoglu, Ibrahim; Guven, Suleyman

    2014-01-01

    Endometrial carcinoma is rarely seen during reproductive ages and commonly related to infertility, polycystic ovarian syndrome (PCOS), and obesity. Pregnancy associated endometrial carcinoma is even rarer and this is the second case reported in the literature concerning tubal pregnancy associated endometrial carcinoma. We present a case of a 36-year-old woman with a history of PCOS, infertility, and several attempts of ovulation induction and in vitro fertilization, who was diagnosed with tubal pregnancy and a well differentiated endometrial carcinoma. We also review the literature about pregnancy associated endometrial carcinoma in the first trimester. PMID:25614844

  4. Childhood body mass index growth trajectories and endometrial cancer risk

    PubMed Central

    Aarestrup, Julie; Gamborg, Michael; Tilling, Kate; Ulrich, Lian G.; Sørensen, Thorkild I.A.

    2016-01-01

    Previously, we found that excess weight already in childhood has positive associations with endometrial cancer; however, associations with changes in body mass index (BMI) during childhood are not well understood. Therefore, we examined whether growth in childhood BMI is associated with endometrial cancer and its sub‐types. A cohort of 155,505 girls from the Copenhagen School Health Records Register with measured weights and heights at the ages of 6–14 years and born 1930–1989 formed the analytical population. BMI was transformed to age‐specific z scores. Using linear spline multilevel models, each girl's BMI growth trajectory was estimated as the deviance from the average trajectory for three different growth periods (6.25–7.99, 8.0–10.99, 11.0–14.0 years). Via a link to health registers, 1,020 endometrial cancer cases were identified, and Cox regressions were performed. A greater gain in BMI during childhood was positively associated with endometrial cancer but no differences between the different growth periods were detected in models adjusted for baseline BMI. The hazard ratios for the associations with overall growth during childhood per 0.1 z score increase were 1.15 (95% confidence interval [CI]: 1.07–1.24) for all endometrial cancers, 1.12 (95% CI: 1.04–1.21) for estrogen‐dependent cancers, 1.16 (95% CI: 1.06–1.26) for endometrioid adenocarcinomas and 1.46 (95% CI: 1.16–1.84) for non‐estrogen‐dependent cancers. Growth in BMI in early life is positively linked to later endometrial cancer risk. We did not identify any sensitive childhood growth period, which suggests that excess gain in BMI during the entire childhood period should be avoided. PMID:27718528

  5. Infant feeding and the incidence of endometrial cancer.

    PubMed

    Xue, Fei; Hilakivi-Clarke, Leena A; Maxwell, G Larry; Hankinson, Susan E; Michels, Karin B

    2008-06-01

    Biological mechanisms could support both an inverse and a direct association between exposure to breast milk in infancy and the risk of cancer. Having been breast-fed has been investigated in relation to the risk of breast and other cancer sites, and conflicting results have been reported. The association between infant feeding and the risk of endometrial cancer has not been explored. From 1976 to 2004, we followed 74,757 cancer-free participants in the Nurses' Health Study who had not undergone hysterectomy. Information on infant feeding was self-reported by study participants. A total of 708 incident cases of endometrial cancer were diagnosed during follow-up. After adjusting for age, family history of endometrial cancer, birth weight, premature birth, and birth order, the incidence of endometrial cancer was not associated with ever having been breast-fed (hazards ratio, 0.94; 95% confidence interval, 0.79-1.11) or duration of having been breast-fed [hazards ratio (95% confidence interval): 1.11 (0.80-1.54), 0.84 (0.62-1.13), 1.02 (0.79-1.31), respectively, for < or =3, 4-8, and > or =9 months of having been breastfed; P for trend = 0.88]. There was no significant effect modification by menopausal status, anthropometric factors (somatotype at age 5 or 10 years, body mass index at age 18 years, or current body mass index), or by other early-life exposures (birth weight, premature birth or exposure to parental smoking in childhood). Additional adjustment for adulthood risk factors of endometrial cancer did not materially change the results. Having been breast-fed was not associated with the incidence of endometrial cancer in this cohort, but statistical power for analyses restricted to premenopausal women was limited.

  6. Changes in microRNA expression levels correlate with clinicopathological features and prognoses in endometrial serous adenocarcinomas.

    PubMed

    Hiroki, Eri; Akahira, Jun-Ichi; Suzuki, Fumihiko; Nagase, Satoru; Ito, Kiyoshi; Suzuki, Takashi; Sasano, Hironobu; Yaegashi, Nobuo

    2010-01-01

    This study aimed to determine the expression profiles of microRNAs (miRNAs) in endometrial serous adenocarcinoma and to examine the association between miRNA expression and clinical outcomes. Twenty-one patients diagnosed with endometrial serous adenocarcinoma between January 2001 and December 2006 were enrolled. miRNA expression profiles were examined using miRNA microarray and qRT-PCR. miRNA expression levels were correlated with clinicopathological variables and survival rates. A total of 120 miRNAs were differentially expressed in endometrial serous adenocarcinoma compared to normal endometria. Of these, 54 miRNAs were down-regulated (>2-fold), including miR-101, miR-10b*, miR-152, and miR-29b, and the remainder were up-regulated (>2-fold), including miR-200a, miR-200b, and miR-205. Decreased expression of miR-10b*, miR-29b, and miR-455-5p was correlated with vascular invasion (P = 0.048, P = 0.013, and P = 0.032, respectively). Univariate analysis revealed that lower expression of miR-101, miR-10b*, miR-139-5p, miR-152, miR-29b, and miR-455-5p was significantly correlated with poor overall survival (P < 0.05), and reduced expression of miR-152, miR-29b, and miR-455-5p was significantly correlated with poor disease-free survival (P < 0.05). Multivariate analysis demonstrated that decreased expression of miR-152 (P = 0.021) was a statistically independent risk factor for overall survival, and decreased expression levels of miR-101 (P = 0.016) and miR-152 (P = 0.010) were statistically independent risk factors for disease-free survival. In addition, transfection of miR-101 or miR-152 precursors into an endometrial serous carcinoma cell line inhibited cell growth (P < 0.0001 and P = 0.01, respectively). Moreover, strong positive immunoreactivity of cyclooxygenase-2 (COX-2) was significantly correlated with down-regulation of miR-101 (P = 0.035). These findings suggest that the dysregulation of miRNAs is associated with the poor prognosis in endometrial serous

  7. [Laparoscopic hysterectomy in the management of endometrial cancer].

    PubMed

    Seracchioli, R; Fabbri, E; Guerrini, M; Mignemi, G; Venturoli, S

    2006-10-01

    Endometrial carcinoma is the most commonly reported gynaecologic malignancy in industrialized countries. Traditionally the surgical treatment of endometrial cancer is total abdominal hysterectomy, bilateral salpingo-oophorectomy, and peritoneal washing cytology. Alternative surgical procedures have been proposed compared to abdominal hysterectomy: increased number of issues about laparoscopy shows the common trend to use this technique. Literature largely described advantages of the laparoscopic procedure compared to abdominal and vaginal surgery. Long-term follow-up series are not available; further investigation into survival and recurrence rates is indicated.

  8. Current Issues in the Diagnosis and Treatment of Endometrial Carcinoma.

    PubMed

    Stubert, J; Gerber, B

    2016-02-01

    Endometrial carcinoma is the most common carcinoma of the female genital tract. Its most important clinical sign is postmenopausal bleeding. An endometrial biopsy is essential for diagnosis. Treatment decisions are governed by tumour risk assessment and patient comorbidity, which is often present. Pelvic and paraaortic lymph node dissection is unnecessary in low risk cases (definition: pT1 a, G1/2) and adjuvant radiotherapy and systemic treatments are usually avoidable. Treatment of high-risk patients (G3 and/or pT1b) and palliative cases is difficult and not well standardised. New molecular-based subtype classification may help treatment decision making in future.

  9. Paraneoplastic cerebellar degeneration as a marker of endometrial cancer recurrence.

    PubMed

    Lie, Geoffrey; Morley, Thomas; Chowdhury, Muhammad

    2016-05-18

    An 84-year-old woman developed a cerebellar syndrome having undergone a total abdominal hysterectomy and bilateral salpingo-oophorectomy for endometrial cancer 1 year previously. She was found to be anti-Yo antibody positive and was diagnosed with paraneoplastic cerebellar degeneration (PCD). A subsequent positron emission tomography scan and lymph node biopsy identified recurrence of her endometrial cancer. This case illustrates how PCD can be an indicator of cancer recurrence, underlines the significance of PCD as a prompt to search for underlying malignancy, and highlights the difficulties PCD poses to the clinician in terms of diagnosis and management.

  10. Instruction dialogues: Teaching new skills to a robot

    NASA Technical Reports Server (NTRS)

    Crangle, Colleen; Suppes, P.

    1989-01-01

    Extended dialogues between a human user and a robot system are presented. The purpose of each dialogue is to teach the robot a new skill or to improve the performance of a skill it already has. The particular interest is in natural language dialogues but the illustrated techniques can be applied to any high level language. The primary purpose is to show how verbal instruction can be integrated with the robot's autonomous learning of a skill.

  11. Ethos in Fukushima and the ICRP dialogue seminars.

    PubMed

    Ando, R

    2016-01-01

    Ethos in Fukushima, a non-profit organisation, participated in 10 of the 12 International Commission on Radiological Protection (ICRP) dialogue seminars over the past 4 years. The slides and videos that were shown at the seminars are recorded on the Ethos in Fukushima website ( http://ethos-fukushima.blogspot.jp/p/icrp-dialogue.html ). I would like to introduce the activities of Ethos in Fukushima to date, and explain why the ICRP dialogue materials have come to be published on its website.

  12. Life-style and metformin for the prevention of endometrial pathology in postmenopausal women.

    PubMed

    Campagnoli, Carlo; Abbà, Chiara; Ambroggio, Simona; Brucato, Tiziana; Pasanisi, Patrizia

    2013-02-01

    In western women, the endometrium is frequently exposed, even after menopause, to the endogenous hormonal stimulation. Such a stimulation increases the risk of pathologic conditions such as endometrial hyperplasia and type I (endometrioid) endometrial adenocarcinoma. Metabolic syndrome, obesity, insulin resistance and type II diabetes promote the endometrial stimulation, and are recognized risk factors for endometrial cancer. Furthermore, chronic hyperinsulinemia linked both to obesity and metabolic syndrome influences endometrial proliferation through direct and indirect actions. Intentional weight loss, calorie restriction and physical activity are associated with a reduced risk of the endometrial pathology. Biological mechanisms include reduction in insulin and sex steroid hormone levels. In addition to life-style modifications, the antidiabetic metformin may be proposed as preventive agent. Metformin reduces the metabolic syndrome, lowers insulin and testosterone levels in postmenopausal women, and it is a potent inhibitor of endometrial cancer cell proliferation.

  13. Reflective scientific sense-making dialogue in two languages: The science in the dialogue and the dialogue in the science

    NASA Astrophysics Data System (ADS)

    Ash, Doris

    2004-11-01

    In this paper I focus on the transition from everyday to scientific ways of reasoning, and on the intertwined roles of meaning-making dialogue and science content as they contribute to scientific literacy. I refer to views of science, and how scientific understanding is advanced dialogically, by Hurd (Science Education, 1998, 82, 402-416), Brown (The Journal of Learning Sciences, 1992, 2(2), 141-178), Bruner (Acts of Meaning, Cambridge, MA: Harvard University Press, 1990), Roth (In J. Brophy (Ed.), Social Constructivist Teaching: Affordances and Constraints (Advances in Research on Teaching Series, Vol. 9), New York: Elsevier/JAI, 2003), and Wells (Dialogic Inquiry: Towards a Sociocultural Practice and Theory of Education, New York: Cambridge University Press, 1999). I argue that family collaborative dialogues in nonschool settings can be the foundations for scientific ways of thinking. I focus on the particular reflective family dialogues at the Monterey Bay Aquarium, when family members remembered and synthesized essential biological themes, centering on adaptation, from one visit to the next, in both Spanish and English. My approach is informed by sociocultural theory, with emphasis on the negotiations of meaning in the zone of proximal development (Vygotsky, 1978), as learners engage in joint productive activity (Tharp & Gallimore, Rousing Minds to Life: Teaching, Learning and Schooling in Social Context, New York: Cambridge University Press, 1988). Over the past decades, researchers have discovered that observing social activity, conversation, and meaning-making in informal settings (Crowley & Callanan, 1997; Guberman, 2002; Rogoff, 2001; Vasquez, Pease-Alvarez, & Shannon, Pushing Boundaries: Language and Culture in a Mexicano Community, New York: Cambridge University Press, 1994) has much to teach us regarding learning in general. To date there has been little research with Spanish-speaking families in informal learning settings and virtually none that

  14. Proteomics of the human endometrial glandular epithelium and stroma from the proliferative and secretory phases of the menstrual cycle.

    PubMed

    Hood, Brian L; Liu, Baoquan; Alkhas, Addie; Shoji, Yutaka; Challa, Rusheeswar; Wang, Guisong; Ferguson, Susan; Oliver, Julie; Mitchell, Dave; Bateman, Nicholas W; Zahn, Christopher M; Hamilton, Chad A; Payson, Mark; Lessey, Bruce; Fazleabas, Asgerally T; Maxwell, G Larry; Conrads, Thomas P; Risinger, John I

    2015-04-01

    Despite its importance in reproductive biology and women's health, a detailed molecular-level understanding of the human endometrium is lacking. Indeed, no comprehensive studies have been undertaken to elucidate the important protein expression differences between the endometrial glandular epithelium and surrounding stroma during the proliferative and midsecretory phases of the menstrual cycle. We utilized laser microdissection to harvest epithelial cells and stromal compartments from proliferative and secretory premenopausal endometrial tissue and performed a global, quantitative mass spectrometry-based proteomics analysis. This analysis identified 1224 total proteins from epithelial cells, among which 318 were differentially abundant between the proliferative and secretory phases (q < 0.05), and 1005 proteins from the stromal compartments, 19 of which were differentially abundant between the phases (q < 0.05). Several proteins were chosen for validation by immunohistochemistry in an independent set of uterine tissues, including carboxypeptidase M, tenascin C, neprilysin, and ectonucleotide pyrophosphatase/phosphodiesterase family member 3 (ENPP3). ENPP3, which was elevated in epithelial glandular cells in the secretory phase, was confirmed to be elevated in midsecretory-phase baboon uterine lavage samples and also observed to have an N-linked glycosylated form that was not observed in the proliferative phase. This study provides a detailed view into the global proteomic alterations of the epithelial cells and stromal compartments of the cycling premenopausal endometrium. These proteomic alterations during endometrial remodeling provide a basis for numerous follow-up investigations on the function of these differentially regulated proteins and their role in reproductive biology and endometrial pathologies.

  15. Building dialogue on complex conservation issues in a conference setting.

    PubMed

    Rock, Jenny; Sparrow, Andrew; Wass, Rob; Moller, Henrik

    2014-10-01

    Dialogue about complex science and society issues is important for contemporary conservation agendas. Conferences provide an appropriate space for such dialogue, but despite its recognized worth, best practices for facilitating active dialogue are still being explored. Face-to-face (FTF) and computer-mediated communication (CMC) are two approaches to facilitating dialogue that have different strengths. We assessed the use of these approaches to create dialogue on cultural perspectives of conservation and biodiversity at a national ecology conference. In particular, we aimed to evaluate their potential to enhance dialogue through their integrated application. We used an interactive blog to generate CMC on participant-sourced issues and to prime subsequent discussion in an FTF conference workshop. The quantity and quality of both CMC and FTF discussion indicated that both approaches were effective in building dialogue. Prior to the conference the blog averaged 126 views per day, and 44 different authors contributed a total of 127 comments. Twenty-five participants subsequently participated in active FTF discussion during a 3-h workshop. Postconference surveys confirmed that CMC had developed participants' thinking and deepened FTF dialogue; 88% indicated specifically that CMC helped facilitate the FTF discussion. A further 83% of respondents concluded that preliminary blog discussion would be useful for facilitating dialogue at future conferences.

  16. Oleic acid promotes the expression of neural markers in differentiated human endometrial stem cells.

    PubMed

    Kojour, Maryam Ali Mohammadie; Ebrahimi-Barough, Somayeh; Kouchesfehani, Homa Mohseni; Jalali, Hanieh; Ebrahim, Mohammah Hosein Karbalaie

    2017-01-01

    Variety of neurodegenerative diseases in humans are caused by loss of cells along with loss of function and disability. Cell replacement therapy is a potential strategy to cure neurodegenerative diseases. Mesenchymal stem cells are pluripotent non-hematopoietic cells that can be isolated from numerous tissues. Human endometrial-derived stem cell (hEnSC) are the abundant and easy available source with no immunological response, for cell replacement therapy. In the nervous system, where fatty acids are found in huge amounts, they participate in its development and maintenance throughout life. Oleic acid is a kind of the saturated fatty acids which plays crucial role in brain development. Oleic acid released by astrocytes is used by neurons for the synthesis of phospholipids and is specifically incorporated into growth cones. Human endometrial-derived stem cells in the third passage were divided into 3 groups including: control, sham (cultured in full differentiation medium without oleic acid) and experimental group (cultured in full differentiation medium with oleic acid) to differentiate over a 18-day period. Data from Real-Time PCR showed that mRNA levels of NF and β-TUBULIN were increased significantly (p<0.05) in oleic acid treated cells in comparison to control and sham groups. Immunocytochemistry analysis of Chat and NF expression also showed the same results. The present study clearly demonstrates that oleic acid promotes neural differentiation of hEnSC through regulation of gene expression.

  17. Endometrial pathology in postmenopausal tamoxifen treatment: comparison between gynaecologically symptomatic and asymptomatic breast cancer patients.

    PubMed Central

    Cohen, I; Perel, E; Flex, D; Tepper, R; Altaras, M M; Cordoba, M; Beyth, Y

    1999-01-01

    AIMS: To evaluate whether endometrial pathology is more likely to be diagnosed in gynaecologically symptomatic rather than in gynaecologically asymptomatic postmenopausal breast cancer patients with tamoxifen treatment; and to evaluate the possible influence of various clinical factors on the incidence of endometrial pathology. METHODS: Endometrial histological findings, transvaginal ultrasonographic endometrial thickness, demographic characteristics, health habits, and risk factors for endometrial cancer were compared between 14 gynaecologically symptomatic (group I) and 224 gynaecologically asymptomatic (group II) postmenopausal breast cancer patients with tamoxifen treatment. RESULTS: Overall, 28.6% of the study population had endometrial pathology. The incidence of overall positive endometrial histological findings was significantly higher in group I than in group II (92.9% v 24.6%, p < 0.0001). Atrophic endometrium was more common in group II than in group I (75.3% v 7.1%, p < 0.0001). Most other endometrial pathology was significantly more common in group I than in group II (endometrial hyperplasia, 35.7% v 5.6%, p < 0.0001; endometrial polyps, 35.7% v 13.4%, p < 0.0111; endometrial carcinoma, 21.5% v 0.9%, p < 0.0001). Endometrial pathology appeared considerably later in the gynaecologically asymptomatic patients than in gynaecologically symptomatic patients (p = 0.0002). Vaginal bleeding or spotting occurred exclusively in group I. The incidence of endometrial pathology in the entire study population was consistent with that reported elsewhere, and higher than that reported for healthy postmenopausal women. CONCLUSIONS: Endometrial pathology is more likely to be diagnosed in gynaecologically symptomatic postmenopausal breast cancer patients with tamoxifen treatment, and after a shorter duration of time, than in gynaecologically asymptomatic patients. PMID:10474520

  18. Pilot study on molecular quantitation and sequencing of endometrial cytokines gene expression and their effect on the outcome of in vitro fertilization (IVF) cycle.

    PubMed

    Sabry, D; Nouh, O; Marzouk, S; Hassouna, A

    2014-09-01

    Human trophoblast invasion and differentiation are essential for successful pregnancy outcome. The molecular mechanisms, however, are poorly understood. Interleukin (IL)-11, a cytokine, regulates endometrial epithelial cell adhesion. Leukemia inhibitory factor (LIF) is one of the key cytokines in the embryo implantation regulation. The present study aimed to assess the levels of LIF, IL-11, and IL-11 α receptor gene expression in the endometrium of women undergoing IVF and correlate their levels with the IVF pregnancy outcome. Also, the study aimed to detect any mutation in these three genes among IVF pregnant and non-pregnant women versus control menstrual blood of fertile women. Endometrial tissue biopsies were taken from 15 women undergoing IVF on the day of oocyte retrieval. The quantitative expression of IL-11, IL-11Rα, and LIF genes was assessed by real-time PCR and PCR products were sequenced. Menstrual blood from 10 fertile women was used as control to compare the DNA sequence versus DNA sequence of the studied genes in endometrial biopsies. LH, FSH, and E2 were assessed for enrolled patients by ELISA. Endometrial thickness was also assessed by pelvic ultrasonography. No significant difference was detected between quantitative expression of the three studied genes and pregnancy IVF outcome. Although DNA sequence changes were found in IL-11 and LIF genes of women with negative pregnancy IVF outcome compared to women with positive pregnancy IVF outcome, no DNA sequence changes were detected for IL-11Rα. Other studied parameters (e.g., age, LH, FSH, E2, and endometrial thickness) showed no significant differences or correlation of quantitative expression of the three studied involved genes. Data suggested that there were no significant differences between quantitative expression of IL-11, IL-11Rα, and LIF genes and the IVF pregnancy outcome. The present study may reveal that changes in IL-11 and LIF genes sequence may contribute in pregnancy IVF outcome.

  19. Leadership and Civil Civic Dialogue across "Enemy" Lines: Promoting the Will for Dialogue

    ERIC Educational Resources Information Center

    Perreault, Geraldine

    2012-01-01

    Leaders often display the all-too-human characteristic of talking only or mostly to people with whom they agree. Yet, to be effective as a leader in many circumstances requires reaching out and engaging in dialogue with those who one may fundamentally disagree and may even view as an enemy. To do so requires a particular conception of leadership,…

  20. Dialogue Journal Bibliography: Published Works about Dialogue Journal Research and Use.

    ERIC Educational Resources Information Center

    Peyton, Joy Kreeft; Staton, Jana

    This annotated bibliography refers to extensive material available for teachers, researchers, and administrators desiring to know more about dialogue journal use and research with many different student populations, from elementary through adult education, regarding teaching English-as-a-Second-Language. It is divided into four sections. Section…

  1. Intrauterine devices and endometrial cancer risk: a pooled analysis of the Epidemiology of Endometrial Cancer Consortium

    PubMed Central

    Felix, Ashley S.; Gaudet, Mia M.; La Vecchia, Carlo; Nagle, Christina M.; Ou Shu, Xiao; Weiderpass, Elisabete; Olov Adami, Hans; Beresford, Shirley; Bernstein, Leslie; Chen, Chu; Cook, Linda S.; De Vivo, Immaculata; Doherty, Jennifer A.; Friedenreich, Christine M.; Gapstur, Susan M.; Hill, Dierdre; Horn-Ross, Pamela L.; Lacey, James V.; Levi, Fabio; Liang, Xiaolin; Lu, Lingeng; Magliocco, Anthony; McCann, Susan E.; Negri, Eva; Olson, Sara H.; Palmer, Julie R.; Patel, Alpa V.; Petruzella, Stacey; Prescott, Jennifer; Risch, Harvey A.; Rosenberg, Lynn; Sherman, Mark E.; Spurdle, Amanda B.; Webb, Penelope M.; Wise, Lauren A.; Xiang, Yong-Bing; Xu, Wanghong; Yang, Hannah P.; Yu, Herbert; Zeleniuch-Jacquotte, Anne; Brinton, Louise A.

    2014-01-01

    Intrauterine devices (IUDs), long-acting and reversible contraceptives, induce a number of immunological and biochemical changes in the uterine environment that could affect endometrial cancer (EC) risk. We addressed this relationship through a pooled analysis of data collected in the Epidemiology of Endometrial Cancer Consortium. We combined individual-level data from 4 cohort and 14 case-control studies, in total 8,801 EC cases and 15,357 controls. Using multivariable logistic regression, we estimated pooled odds ratios (pooled-ORs) and 95% confidence intervals (CIs) for EC risk associated with ever use, type of device, ages at first and last use, duration of use, and time since last use, stratified by study and adjusted for confounders. Ever use of IUDs was inversely related to EC risk (pooled-OR=0.81, 95% CI=0.74–0.90). Compared with never use, reduced risk of EC was observed for inert IUDs (pooled-OR=0.69, 95% CI=0.58–0.82), older age at first use (≥35 years pooled-OR=0.53, 95% CI=0.43–0.67), older age at last use (≥45 years pooled-OR=0.60, 95% CI=0.50–0.72), longer duration of use (≥10 years pooled-OR=0.61, 95% CI=0.52–0.71), and recent use (within 1 year of study entry pooled-OR=0.39, 95% CI=0.30–0.49). Future studies are needed to assess the respective roles of detection biases and biologic effects related to foreign body responses in the endometrium, heavier bleeding (and increased clearance of carcinogenic cells), and localized hormonal changes. PMID:25242594

  2. GUIDE: Graduates United in Dialogue for Excellence.

    PubMed

    Price, Sheri; Forgeron, Paula; MacConnell, Grace

    2008-07-01

    Graduate school can be stressful and overwhelming for students. A supportive atmosphere that promotes mentoring and networking can ameliorate the stress associated with returning to the academic environment. This article describes the process by which a group of students created a dynamic forum for the sharing of ideas, collaboration, mentoring, networking, and research among master's-prepared nurses. To reflect these ideals, the forum was entitled "Graduates United In Dialogue for Excellence" (GUIDE). The monthly GUIDE forums provided an environment in which students could learn from exchanging ideas and sharing experiences with one another, faculty, and other nursing leaders. GUIDE was successful in fostering professional growth and collaboration, thus benefiting all participants.

  3. The battle over retail competition: A dialogue

    SciTech Connect

    1994-06-01

    This article presents the results of a dialogue between eight individuals and organizations to address a set of questions presented by the journal, dealing with the general issue of wheeling, which is inducing strong stands within the industry, and governmental sector at the present time. The article is presented to provide insights into this question from a number of different perspectives, to help those looking at this issue to get a handle on the different perceived impacts of this type of a regulatory policy.

  4. Navy Plastics Dialogue, Modification Number 2

    DTIC Science & Technology

    1993-09-28

    the Navy Washington, D.C. 20350-2000 703-602-2562 Fax: 703-602-4642 Tom Ledvina Navy Deputy Assistant General Counsel (I&E) 5 Room 368 Crystal Plaza #5...a whistleblower number. The Navy staff responded that the Naval Inspector does have such a mechanism with its 800 number hotline. Captain Tom Ledvina ...Dialogue has accomplished from both Navy and non-Navy members. The first item on the agenda was the Navy’s Report to Congress. Tom Ledvina , Navy Deputy

  5. Oestrogen-induced epithelial-mesenchymal transition of endometrial epithelial cells contributes to the development of adenomyosis.

    PubMed

    Chen, Yi-Jen; Li, Hsin-Yang; Huang, Chi-Hung; Twu, Nae-Fang; Yen, Ming-Shyen; Wang, Peng-Hui; Chou, Teh-Ying; Liu, Yen-Ni; Chao, Kuan-Chong; Yang, Muh-Hwa

    2010-11-01

    Adenomyosis is an oestrogen-dependent disease caused by a downward extension of the endometrium into the uterine myometrium. Epithelial-mesenchymal transition (EMT) endows cells with migratory and invasive properties and can be induced by oestrogen. We hypothesized that oestrogen-induced EMT is critical in the pathogenesis of adenomyosis. We first investigated whether EMT occurred in adenomyotic lesions and whether it correlated with serum 17β-oestradiol (E2) levels. Immunohistochemistry was performed on adenomyotic lesions and corresponding eutopic endometrium samples from women with adenomyosis. Endometria from women without endometrial disorders were used as a control. In the epithelial component of adenomyotic lesions, vimentin expression was up-regulated and E-cadherin expression was down-regulated compared to the eutopic endometrium, suggesting that EMT occurs in adenomyosis. In adenomyosis, the serum E2 level was negatively correlated with E-cadherin expression in the epithelial components of the eutopic endometrium and adenomyotic lesions, suggesting the involvement of oestrogen-induced EMT in endometrial cells. In oestrogen receptor-positive Ishikawa endometrial epithelial cells, oestrogen induced a morphological change to a fibroblast-like phenotype, a shift from epithelial marker expression to mesenchymal marker expression, increased migration and invasion, and up-regulation of the EMT regulator Slug. Raloxifene, a selective oestrogen receptor modulator, abrogated these effects. To determine the role of oestrogen-induced EMT in the implantation of ectopic endometrium, we xenotransplanted eutopic endometrium or adenomyotic lesions from adenomyosis patients into ovariectomized SCID mice. The implantation of endometrium was oestrogen-dependent and was suppressed by raloxifene. Collectively, these data highlight the crucial role of oestrogen-induced EMT in the development of adenomyosis and suggest that raloxifene may be a potential therapeutic agent for

  6. Molecular Biology and Prevention of Endometrial Cancer. Addendum

    DTIC Science & Technology

    2008-07-01

    gain insight into the biologic mechanism underlying the chemopreventive effect of the oral contraceptive pill (OCP). Project 1: Objectives completed...oral contraceptive pill and hormone replacement therapy on reproductive organs. This objective has been completed and the results were submitted...protective effect of oral contraceptive (OC) therapy. Methods: 1) Oligonucleotide microarray analysis was performed on a panel of endometrial cancers

  7. Small non-coding RNA deregulation in endometrial carcinogenesis

    PubMed Central

    Ravo, Maria; Cordella, Angela; Rinaldi, Antonio; Bruno, Giuseppina; Alexandrova, Elena; Saggese, Pasquale; Nassa, Giovanni; Giurato, Giorgio; Tarallo, Roberta; Marchese, Giovanna; Rizzo, Francesca; Stellato, Claudia; Biancardi, Rossella; Troisi, Jacopo; Di Spiezio Sardo, Attilio; Zullo, Fulvio; Weisz, Alessandro; Guida, Maurizio

    2015-01-01

    Small non-coding RNAs (sncRNAs) represent a heterogeneous group of <200nt-long transcripts comprising microRNAs, PIWI-interacting RNAs (piRNAs) and small-nucleolar-RNAs (snoRNAs) involved in physiological and pathological processes such as carcinogenesis and tumor progression. Aberrant sncRNA expression in cancer has been associated with specific clinical phenotypes, grading, staging, metastases development and resistance to therapy. Aim of the present work is to study the role of sncRNAs in endometrial carcinogenesis. Changes in sncRNA expression were identified by high-throughput genomic analysis of paired normal, hyperplastic and cancerous endometrial tissues obtained by endometrial biopsies (n = 10). Using smallRNA sequencing and microarrays we identified significant differences in sncRNA expression pattern between normal, hyperplastic and neoplastic endometrium. This led to the definition of a sncRNA signature (129 microRNAs, 2 of which not previously described, 10 piRNAs and 3 snoRNAs) of neoplastic transformation. Functional bioinformatics analysis identified as downstream targets multiple signaling pathways potentially involved in the hyperplastic and neoplastic tissue responses, including Wnt/β-catenin, and ERK/MAPK and TGF-β-Signaling. Considering the regulatory role of sncRNAs, this newly identified sncRNA signature is likely to reflect the events leading to endometrial cancer, which can be exploited to dissect the carcinogenic process including novel biomarkers for early and non-invasive diagnosis of these tumors. PMID:25686835

  8. Treatment of endometrial hyperplasia with levonorgestrel releasing intrauterine devices.

    PubMed

    Perino, A; Quartararo, P; Catinella, E; Genova, G; Cittadini, E

    1987-01-01

    The effectiveness of a new levo-norgestrel releasing intrauterine device is assessed in fourteen patients with histologically confirmed hyperplastic lesions of the endometrial mucosa. The morphologic response of the hyperplastic endometria to the action of the levo-norgestrel in this study explains the regression of the cases so treated.

  9. Utility of immunohistochemistry in predicting microsatellite instability in endometrial carcinoma.

    PubMed

    Modica, Ippolito; Soslow, Robert A; Black, Destin; Tornos, Carmen; Kauff, Noah; Shia, Jinru

    2007-05-01

    Identification of the microsatellite instability (MSI) phenotype in endometrial carcinoma is important given that such tumors are the most common noncolorectal tumors to occur in hereditary nonpolyposis colorectal cancer syndrome, and may bear prognostic relevance. The objective of this study was to assess the utility of immunohistochemistry (IHC), a simple and fast technique, in detecting MSI in endometrial carcinoma. The study subjects consisted of 90 endometrial carcinoma patients with equal representation of MSI-high (MSI-H) and non-MSI-H tumors. MSI was tested using the standard polymerase chain reaction-based method and the 5 NCI-recommended markers. Overall, IHC with MLH1 and MSH2 antibodies detected 69% of MSI-H tumors with a specificity of 100%. Adding PMS2 and MSH6 to the antibody panel increased the sensitivity to 91% but decreased the specificity to 83%. The most common IHC abnormality in MSI tumors was concurrent loss of MLH1/PMS2. Assessment of staining was straightforward in most cases but not in all. Staining inadequacies existed. Five stains (4 MLH1 and 1 MSH6) were not interpretable because of the lack of any internal positive control. Two percent to 10% of the cases (depending on the antibody assessed) had only focal weak staining; the highest frequency (10%) occurred with MLH1 antibody. PMS2 staining detected 7 MLH1-staining present MSI-H cases, thus partly accounting for the increased sensitivity with the 4-antibody panel. MSH6 staining identified 9 cases with loss of MSH6 alone, 6 of 9 were non-MSI-H, thus partly accounting for the decreased specificity with the 4-antibody panel. In conclusion, our results suggest that IHC is useful in detecting MSI in endometrial carcinoma. Although IHC has a lower sensitivity with more apparent staining inadequacies in detecting MSI in endometrial carcinoma than it does in colorectal carcinoma, its use in endometrial carcinoma may be an important adjunct when screening for hereditary cases. In the future, as

  10. DISCUSS: Toward a Domain Independent Representation of Dialogue

    ERIC Educational Resources Information Center

    Becker, Lee

    2012-01-01

    While many studies have demonstrated that conversational tutoring systems have a positive effect on learning, the amount of manual effort required to author, design, and tune dialogue behaviors remains a major barrier to widespread deployment and adoption of these systems. Such dialogue systems must not only understand student speech, but must…

  11. The Difficult Dialogues Initiative at Clark University: A Case Study

    ERIC Educational Resources Information Center

    Buie, Sarah; Wright, Walter

    2010-01-01

    For the last five years, the Higgins School of Humanities has worked to develop a culture of dialogue at Clark University through its Difficult Dialogues Initiative. People know that genuine communication, creative collaboration, and effective problem solving are necessary to address the challenges they face as a nation and world; a renewed…

  12. Socratic Dialogue, the Humanities and the Art of the Question

    ERIC Educational Resources Information Center

    Mitchell, Sebastian

    2006-01-01

    Plato's depiction of Socrates' interrogations in his early dialogues provides an enduring example of the importance of asking questions as an educative method. This article considers the central educational elements of Socratic dialogue and the ways in which these were developed in the 20th century, particularly in "The Socratic Method"…

  13. "He Said What?!" Constructed Dialogue in Various Interface Modes

    ERIC Educational Resources Information Center

    Young, Lesa; Morris, Carla; Langdon, Clifton

    2012-01-01

    This study analyzes the manifestation of constructed dialogue in ASL narratives as dependent on the interface mode (i.e., face-to-face conversation, electronic conversation over videophone, and vlog monologues). Comparisons of eye gaze over three interface modes shows how aspects of constructed dialogue are altered to fit the communication mode.…

  14. Russian Basic Course: Dialogue Cartoon Guides, Lessons 1-83.

    ERIC Educational Resources Information Center

    Defense Language Inst., Washington, DC.

    This booklet of cartoon guides contains 83 units of instructional materials prepared by the Defense Language Insitute for use in an intensive, conversational, Russian course. Included are cartoon guides to dialogues and dialogue recombinations which focus on social concerns and military matters. (RL)

  15. The Dialogue Journal: A Tool for Building Better Writers

    ERIC Educational Resources Information Center

    Denne-Bolton, Sara

    2013-01-01

    Using dialogue journals gives English language learners valuable writing practice. This article explores topics such as audience, fluency, teacher-student relationships, empowerment, and making the connection to academic writing. And the author gives practical advice on how teachers can institute dialogue journals in their classrooms and how best…

  16. Socrates Lives: Dialogue as a Means of Teaching and Learning

    ERIC Educational Resources Information Center

    Moberg, Eric M.

    2008-01-01

    The purpose of this paper is to argue for the ongoing use of dialogue as a modern pedagogical and andragogical method. The author reviewed 18 scholarly sources from three education databases in this literature review. The use of dialogue as mode of instruction dates from the Socratic Method of 399 B.C.E. to present uses. The literature reveals…

  17. Using Intergroup Dialogue to Promote Social Justice and Change

    ERIC Educational Resources Information Center

    Dessel, Adrienne; Rogge, Mary E.; Garlington, Sarah B.

    2006-01-01

    Intergroup dialogue is a public process designed to involve individuals and groups in an exploration of societal issues such as politics, racism, religion, and culture that are often flashpoints for polarization and social conflict. This article examines intergroup dialogue as a bridging mechanism through which social workers in clinical, other…

  18. An Investigation into Participation in Classroom Dialogue in Mainland China

    ERIC Educational Resources Information Center

    Song, Yu

    2015-01-01

    Classroom dialogue is commonly used in teaching and learning, and viewed as in terms of helping students to think critically and understand knowledge better. Thus, educators and scholars call on active participation in classroom dialogue. However, students in mainland China are traditionally viewed as less talkative in class. In this study, I…

  19. Dialogue on Modernity and Modern Education in Dispute

    ERIC Educational Resources Information Center

    Baker, Michael; Peters, Michael A.

    2012-01-01

    This is a dialogue or conversation between Michael Baker (MB) and Michael A. Peters (MP) on the concept of modernity and its significance for educational theory. The dialogue took place originally as a conversation about a symposium on modernity held at the American Educational Studies Association meeting 2010. It was later developed for…

  20. Democracy in Education through Community-Based Policy Dialogues

    ERIC Educational Resources Information Center

    Winton, Sue

    2010-01-01

    In 2008, People for Education, an Ontario-based parent-led organization, hosted eight policy dialogues with citizens about possibilities for the province's public schools. Policy dialogues are conversations about policy issues, ideas, processes, and outcomes where participants share their knowledge, perspectives, and experiences. In small groups…

  1. Annotation of Tutorial Dialogue Goals for Natural Language Generation

    ERIC Educational Resources Information Center

    Kim, Jung Hee; Freedman, Reva; Glass, Michael; Evens, Martha W.

    2006-01-01

    We annotated transcripts of human tutoring dialogue for the purpose of constructing a dialogue-based intelligent tutoring system, CIRCSIM-Tutor. The tutors were professors of physiology who were also expert tutors. The students were 1st year medical students who communicated with the tutors using typed communication from separate rooms. The tutors…

  2. The High Stakes of Artificial Dialogue in Teacher Education

    ERIC Educational Resources Information Center

    Simpson, Douglas J.

    2009-01-01

    Talking about important events, experiences, and ideas is a crucial societal concern for many reasons. In the field of teacher education, dialogue may be even more difficult because it is sometimes seen as being both essential and troubling. Dialogue is complicated because some people are fearful of open inquiry; others are inclined to rant; and…

  3. Intergroup Dialogue: Education for a Broad Conception of Civic Engagement

    ERIC Educational Resources Information Center

    Gurin, Patricia; Nagda, Biren A.; Sorensen, Nicholas

    2011-01-01

    Intergroup dialogue provides what students need in order to relate and collaborate across differences, something they have to do in community projects that usually involve interactions across racial, social class, religious, and geographical divides. In this article, the authors demonstrate the efficacy of intergroup dialogue, drawing from a…

  4. Collaborative Learning and Dialogue: Democratic Learning in Adult Education

    ERIC Educational Resources Information Center

    Armstrong, Joseph; Hyslop-Margison, Emery

    2006-01-01

    Building on the framework of Peters and Armstrong's (1998) three Types of Teaching/Learning, this article explores the use of dialogue to foster a collaborative and democratic learning experience. There are three conditions under which dialogue can be facilitated as a part of the collaborative learning experience: (a) intent, (b) a dialogical…

  5. Dialogue as Moral Paradigm: Paths toward Intercultural Transformation

    ERIC Educational Resources Information Center

    Keller, J. Gregory

    2011-01-01

    The Council of Europe's 2008 "White Paper on Intercultural Dialogue: 'living together as equals in dignity'" points to the need for shared values upon which intercultural dialogue might rest. In order, however, to overcome the monologic separateness that threatens community, we must educate ourselves to recognize the dialogism of our…

  6. A Case Study of Epistemic Order in Mathematics Classroom Dialogue

    ERIC Educational Resources Information Center

    Ruthven, Kenneth; Hofmann, Riikka

    2016-01-01

    We define epistemic order as the way in which the exchange and development of knowledge takes place in the classroom, breaking this down into a system of three components: epistemic initiative relating to who sets the agenda in classroom dialogue, and how; epistemic appraisal relating to who judges contributions to classroom dialogue, and how; and…

  7. Practical Implementation of "Soka" Education: A Dialogue with Monte Joffee

    ERIC Educational Resources Information Center

    Joffee, Monte; Goulah, Jason; Gebert, Andrew

    2009-01-01

    This article presents a dialogue with Monte Joffee. Joffee has been an active leader in the small school and charter school movements in New York City for over 20 years. He is a cofounder of The Renaissance Charter School in New York City and served as its founding principal (1993-2007). In this dialogue, Joffee articulates the ways in which…

  8. Learning through Personal Connections: Cogenerative Dialogues in Synchronous Virtual Spaces

    ERIC Educational Resources Information Center

    Bondi, Stephanie; Daher, Tareq; Holland, Amy; Smith, Adam R.; Dam, Stacy

    2016-01-01

    This study describes the role of cogenerative dialogues in a synchronous virtual classroom. Cogenerative dialogues are a way for students and instructors to reflect upon in-class events and work collaboratively during the course to optimize teaching and learning. In the present study, cogen has been found to be a tool for enhancing connections…

  9. Exploring Creative Thinking in Graphically Mediated Synchronous Dialogues

    ERIC Educational Resources Information Center

    Wegerif, Rupert; McLaren, Bruce M.; Chamrada, Marian; Scheuer, Oliver; Mansour, Nasser; Miksatko, Jan; Williams, Mriga

    2010-01-01

    This paper reports on an aspect of the EC funded Argunaut project which researched and developed awareness tools for moderators of online dialogues. In this study we report on an investigation into the nature of creative thinking in online dialogues and whether or not this creative thinking can be coded for and recognized automatically such that…

  10. Analyzing Empirical Notions of Suffering: Advancing Youth Dialogue and Education

    ERIC Educational Resources Information Center

    Baring, Rito V.

    2010-01-01

    This article explores the possibilities of advancing youth dialogue and education among the Filipino youth using empirical notions of students on suffering. Examining empirical data, this analysis exposes uncharted notions of suffering and shows relevant meanings that underscore the plausible trappings of youth dialogue and its benefits on…

  11. Bakhtin and Freire: Dialogue, Dialectic and Boundary Learning

    ERIC Educational Resources Information Center

    Rule, Peter

    2011-01-01

    Dialogue is a seminal concept within the work of the Brazilian adult education theorist, Paulo Freire, and the Russian literary critic and philosopher, Mikhail Bakhtin. While there are commonalities in their understanding of dialogue, they differ in their treatment of dialectic. This paper addresses commonalities and dissonances within a…

  12. The Socratic Dialogue in Asynchronous Online Discussions: Is Constructivism Redundant?

    ERIC Educational Resources Information Center

    Kingsley, Paul

    2011-01-01

    Purpose: This paper aims to examine Socratic dialogue in asynchronous online discussions in relation to constructivism. The links between theory and practice in teaching are to be discussed whilst tracing the origins of Socratic dialogue and recent trends and use of seminar in research based institutions. Design/methodology/approach: Many online…

  13. Dialogue: The Key to Professionalism in Technical Communication.

    ERIC Educational Resources Information Center

    Sims, R. L.

    The key to producing professional quality documents is the dialogue between writers and editors. Such a dialogue should include six major components: genuineness, accurate empathetic understanding, unconditional positive regard, presentness, a spirit of mutual equality, and a supportive psychological climate. Such an atmosphere was created at one…

  14. A Response to Jane Sahi's "Dialogue as Education: Martin Buber"

    ERIC Educational Resources Information Center

    Baniwal, Vikas

    2014-01-01

    This article is inspired by Jane Sahi's commentary, "Dialogue as Education: Martin Buber," published under the feature "Classics with Commentary" in the Monsoon 2005 issue of "Contemporary Education Dialogue." I seek to further the discussion of the contributions of Martin Buber to the discourse of education through…

  15. Furthering the Goal of Cross-Disciplinary Dialogue

    ERIC Educational Resources Information Center

    Moss, Pamela A.; Pullin, Diana; Gee, James Paul; Haertel, Edward H.

    2005-01-01

    This article presents a rejoinder on the commentaries of the authors' article titled, "The Idea of Testing: Psychometric and Sociocultural Perspectives." In different ways, each commentary has made a productive contribution to a multidisciplinary dialogue about educational assessment. The authors acknowledge that dialogue across disciplinary…

  16. Understanding Student Language: An Unsupervised Dialogue Act Classification Approach

    ERIC Educational Resources Information Center

    Ezen-Can, Aysu; Boyer, Kristy Elizabeth

    2015-01-01

    Within the landscape of educational data, textual natural language is an increasingly vast source of learning-centered interactions. In natural language dialogue, student contributions hold important information about knowledge and goals. Automatically modeling the dialogue act of these student utterances is crucial for scaling natural language…

  17. Including Psychology in Inclusive Pedagogy: Enriching the Dialogue?

    ERIC Educational Resources Information Center

    Kershner, Ruth

    2016-01-01

    Inclusive education is a complex field of study and practice that requires good communication and dialogue between all involved. Psychology has to some extent been marginalised in these educational dialogues. This is, in part, due to psychology's perceived heritage in the standardised testing that has been used to support the educational…

  18. A Dialogue: Our Selves, Our Students, and Obama

    ERIC Educational Resources Information Center

    McLaughlin, Jennifer; Kelly, Kim

    2009-01-01

    The following essay is a dialogue between two high school English teachers at a small, progressive public school on the Lower East Side of Manhattan. Throughout their dialogue, Jen, whose voice appears in italics, and Kim, whose voice appears in plain text, discuss the factors that motivated their decisions to become teachers, tell of the distinct…

  19. Endometrial safety of hormone replacement therapy: review of literature.

    PubMed

    Van Gorp, Toon; Neven, Patrick

    2002-06-25

    Unopposed estrogens for treating menopausal symptoms were extensively used when epidemiological findings associated them with an increased endometrial cancer risk. Adding progestogens reverse this side effect efficiently but patient, dose, type and especially time during which the progestogen is administered are important. Long-term uterine safety of the long cycle HRT with administration of the progestogen every 3 months remains unclear. Because regular bleeding lowers compliance, continuous combined estrogen-progestogen treatment has become popular. Many different regimens are now available using oral, transdermal, subcutaneous, intravaginal or intra-uterine application of the estrogen and/or progestogen. Available but inadequate studies seem to point towards a slightly decreased endometrial cancer risk with continuous combined preparations compared with non-HRT-users and an increased risk with long-term oral but not vaginal treatment with low-potency estrogen formulations such as estriol. Newer compounds for menopausal health such as tibolone and raloxifene seem to be safe. As for any women with abnormal vaginal bleeding, those on HRT must have an intra-uterine evaluation. Transvaginal ultrasound (TVU) is very accurate in predicting a normal uterine cavity but inaccurate in predicting endometrial pathology because of a low specificity and positive predictive value of a thick echogenic endometrium. In all such cases a three-dimensional visualisation of intra-uterine lesions is more accurate. Periodic examination with TVU and/or endometrial biopsy of HRT exposed endometrium in asymptomatic women is not cost-effective. The available limited data on the use of HRT in hysterectomised women for early stage endometrial cancer show little evidence in terms of recurrence.

  20. Endometrial cancer and meat consumption: a case-cohort study.

    PubMed

    van Lonkhuijzen, Luc; Kirsh, Victoria A; Kreiger, Nancy; Rohan, Thomas E

    2011-07-01

    Diet plays an important role in the etiology of certain cancers, but there is limited evidence with regard to the association between diet and risk of endometrial cancer. Few prospective studies have investigated meat intake as a potential determinant of endometrial cancer risk. The objective of this study was to examine the association between endometrial cancer risk and total meat, red meat, processed meat, fish, and poultry intake. We conducted a case-cohort analysis within the Canadian Study of Diet, Lifestyle, and Health, a prospective cohort of 73 909 adults (39 614 women). Participants were recruited from 1992 to 1999, predominantly from three Canadian universities. We conducted a linkage with the Ontario Cancer Registry for the years 1992-2007 for the female cohort members, who resided in Ontario at the time of enrollment (n=26 024), to yield data on cancer incidence. The analytic sample was comprised of 107 incident cases and 1830 subcohort members, the latter being an age-stratified sample of the full cohort. A nonsignificant increase in the risk of endometrial cancer was associated with increased consumption of red meat [hazard ratio (HR)=1.62, 95% confidence intervals (CI)=0.86-3.08, for high vs. low intake; P trend=0.13)], processed meat (HR=1.45, 95% CI=0.80-2.61, for high vs. low intake; P trend=0.058), and all meat combined (HR=1.50, 95% CI=0.78-2.89, for high vs. low intake; P trend=0.14). No clear patterns were noted for poultry or fish. The results of this study, although based on a limited number of cases, suggest that relatively high meat intake may be associated with increased risk of endometrial cancer.

  1. Soy Intake Is Associated With Lower Endometrial Cancer Risk

    PubMed Central

    Zhang, Guo-Qiang; Chen, Jin-Liang; Liu, Qin; Zhang, Yong; Zeng, Huan; Zhao, Yong

    2015-01-01

    Abstract Epidemiologic studies reporting the effect of soy intake on endometrial cancer risk conveyed conflicting results. We systematically reviewed the literature to investigate whether there was an inverse relation between dietary soy intake and endometrial cancer risk. PubMed, EMBASE, the Cochrane Library, and 4 main Chinese literature databases were searched from their inception to August 25, 2015 for both case–control studies and cohort studies that assessed the effect of soy intake on endometrial cancer risk. Study-specific most-adjusted odds ratios (ORs) or relative risks (RRs) were combined by using fixed-effects or random-effects model to calculate pooled risk estimates (REs). A total of 10 epidemiologic studies were included in this meta-analysis, including 8 case–control studies and 2 prospective cohort studies. Dietary soy intake was inversely associated with endometrial cancer risk with an overall RE of 0.81 (95% CI: 0.72, 0.91). In subgroup analyses, a statistically significant protective effect of soy intake was found for unfermented soy food (RE: 0.81, 95% CI: 0.67, 0.97), postmenopausal women (RE: 0.76, 95% CI: 0.61, 0.95), and Asian (RE: 0.79, 95% CI: 0.66, 0.95) and non-Asian population (RE: 0.83, 95% CI: 0.71, 0.96). Current evidence indicates that soy food intake is associated with lower endometrial cancer risk. Further larger cohort studies are warranted to fully clarify such an association. PMID:26683956

  2. Endometrial metaplasias and reactive changes: a spectrum of altered differentiation.

    PubMed

    Nicolae, Alina; Preda, Ovidiu; Nogales, Francisco F

    2011-02-01

    Endometrial metaplasias and changes (EMCs) are conditions frequently overlooked and misdiagnosed. The aim of this review is to update current issues and provide a classification with a practical clinicopathological approach. Hormonal or irritative stimuli are the main inducing factors of EMCs, although some metaplasias have a mutational origin. EMCs vary from reactive, degenerative lesions to those able to associate with malignancy or those having a preneoplastic potential. The most common types of EMCs are ciliated tubal metaplasia (CTM) and mucinous metaplasia (MM), which occur in simple and complex glands, and possibly these architectural changes hold the same prognostic significance as they do in hyperplastic endometrioid lesions. Immunohistochemically, CTM is positive for LhS28, bcl-2, PAX2 and p16(INK4A). Complex CTM is likely to be a precursor of ciliated endometrioid-type carcinomas. MMs should be evaluated architecturally, taking into account that their atypicality is minimal. The differentiation between complex MM and mucinous carcinoma may be extremely difficult. Surface complex, papillary MM in endometrial polyps can be considered as benign. Intestinal-type endometrial MM is rare and its presence should prompt further investigation of associated lesions in the endocervix. Endometrial squamous metaplasia (ESS) is often linked to chronic irritative situations. It should be differentiated from secondary involvement by a human papilomavirus-related cervical lesion. Morular metaplasia is a mutational phenomenon with a distinct phenotype that helps to differentiate it from ESS. Morules are benign, hormonally inert structures that are often markers of complex endometrioid glandular architecture, and they are associated with an attenuated malignancy. Endometrial reactive changes are commonly associated with desquamation or hormonal imbalance. The frequent, p16(INK4A) positive, benign surface papillary syncytial change may be misdiagnosed, in some cases, as

  3. Evaluation of two endometriosis models by transplantation of human endometrial tissue fragments and human endometrial mesenchymal cells

    PubMed Central

    Jafarabadi, Mina; Salehnia, Mojdeh; Sadafi, Rana

    2017-01-01

    Background: The animal models of endometriosis could be a valuable alternative tool for clarifying the etiology of endometriosis. Objective: In this study two endometriosis models at the morphological and molecular levels was evaluated and compared. Materials and Methods: The human endometrial tissues were cut into small fragments then they were randomly considered for transplantation into γ irradiated mice as model A; or they were isolated and cultured up to fourth passages. 2×106 cultured stromal cells were transplanted into γ irradiated mice subcutaneously as model B. twenty days later the ectopic tissues in both models were studied morphologically by Periodic acid-Schiff and hematoxylin and eosin staining. The expression of osteopontin (OPN) and matrix metalloproteinase 2 (MMP2) genes were also assessed using real time RT-PCR. 17-β estradiol levels of mice sera were compared before and after transplantation. Results: The endometrial like glands and stromal cells were formed in the implanted subcutaneous tissue of both endometriosis models. The gland sections per cubic millimeter, the expression of OPN and MMP2 genes and the level of 17-β estradiol were higher in model B than model A (p=0.03). Conclusion: Our observation demonstrated that endometrial mesenchymal stromal cells showed more efficiency to establish endometriosis model than human endometrial tissue fragments. PMID:28280797

  4. The incidence rates of endometrial hyperplasia and endometrial cancer: a four-year population-based study

    PubMed Central

    2016-01-01

    Introduction The aim of this study was to determine the incidence rates of endometrial hyperplasia (EH) and endometrial cancer (EC) in the Republic of Korea using national insurance claim data generated from 2009 to 2012. Materials and Methods Data that were generated from 2009 to 2012 were sourced from the Korean Health Insurance Review and Assessment Service-National Inpatients Sample database. The data from women who were assigned diagnosis codes representing EH or EC within 1 month of being assigned codes that corresponded to procedures that included endometrial biopsies and several types of gynecologic surgeries to obtain endometrial pathology samples, were selected for analysis. Results Data from 2,477,424 women were entered into the database between 2009 and 2012, and the data from 1,868 women with EH and 868 women with EC were extracted for analysis. The mean ages of the patients were 44.1 ± 0.4 years for those with EH and 52.7 ± 0.6 years for those with EC. The EH and EC incidence rates were 37 per 100,000 woman-years and 8 per 100,000 woman-years, respectively. The EH and EC incidence rates peaked when the women were in their late forties and fifties, respectively. Conclusions The EH and EC incidence rates determined in this study were somewhat lower than those determined from previous studies. Further studies are required that adjust the data for race, menopausal hormone therapy, and obesity. PMID:27635340

  5. Effective use of critique and dialogue at scholarly conferences.

    PubMed

    DeMarco, Rosanna F; Horowitz, June Andrews; McCurry, Mary K

    2005-01-01

    In this article, the authors offer a solution to a phenomenon identified as "silencing" among nurse colleagues during national, regional, and international scholarly conferences. Through an electronic anonymous survey, data were collected regarding perceptions of the structure and process at scholarly nursing conferences. The need for critique and dialogue while sharing research ideas or findings is identified as a means to encourage direct exchange at professional conferences. Based on an examination of the process of critique and dialogue, and theories that explain why honest and direct dialogue are sometimes subdued, the authors propose a model of constructive scholarly dialogue for conference participation. The goals of implementing this model are to make scholarly exchanges normative at nursing conferences, and to revise standard conference formats so that constructive critique and dialogue are encouraged actively. The likely outcomes include improved nursing science and professional development of nurses.

  6. Using intergroup dialogue to promote social justice and change.

    PubMed

    Dessel, Adrienne; Rogge, Mary E; Garlington, Sarah B

    2006-10-01

    Intergroup dialogue is a public process designed to involve individuals and groups in an exploration of societal issues such as politics, racism, religion, and culture that are often flashpoints for polarization and social conflict. This article examines intergroup dialogue as a bridging mechanism through which social workers in clinical, other direct practice, organizer, activist, and other roles across the micro-macro practice spectrum can engage with people in conflict to advance advocacy, justice, and social change. We define intergroup dialogue and provide examples in not-for-profit or community-based and academic settings of how intergroup dialogue has been applied to conflicts around topics of race and ethnic nationality, sexual orientation, religion, and culture. We recommend practice-, policy-, and research-related actions that social workers can take to understand and use intergroup dialogue.

  7. Heterosexual students' experiences in sexual orientation intergroup dialogue courses.

    PubMed

    Dessel, Adrienne B; Woodford, Michael R; Routenberg, Robbie; Breijak, Duane P

    2013-01-01

    Heterosexism contributes to an unsafe campus climate for lesbian, gay, and bisexual (LGB) college students. Intergroup dialogue courses about sexual orientation seek to build awareness, cross-group relationships, and commitment to social action to address anti-LGB prejudice and discrimination. Although dialogue courses are growing in popularity, few courses address sexual orientation. To advance knowledge of these dialogues, this qualitative study explores heterosexual students' motivations and expectations, challenges, and learning outcomes related to their participation in intergroup dialogue courses on sexual orientation. Core themes include desire to learn about the LGB community, concerns about offending classmates, anxiety around LGB stigma, conflict with classmates around controversial topics, affirming LGB people, and learning about heterosexism, privilege, and intersectionality of identity. Implications for intergroup dialogue pedagogy and research are discussed.

  8. Disfluency in dialogue: an intentional signal from the speaker?

    PubMed

    Finlayson, Ian R; Corley, Martin

    2012-10-01

    Disfluency is a characteristic feature of spontaneous human speech, commonly seen as a consequence of problems with production. However, the question remains open as to why speakers are disfluent: Is it a mechanical by-product of planning difficulty, or do speakers use disfluency in dialogue to manage listeners' expectations? To address this question, we present two experiments investigating the production of disfluency in monologue and dialogue situations. Dialogue affected the linguistic choices made by participants, who aligned on referring expressions by choosing less frequent names for ambiguous images where those names had previously been mentioned. However, participants were no more disfluent in dialogue than in monologue situations, and the distribution of types of disfluency used remained constant. Our evidence rules out at least a straightforward interpretation of the view that disfluencies are an intentional signal in dialogue.

  9. The expression of S100P increases and promotes cellular proliferation by increasing nuclear translocation of β-catenin in endometrial cancer.

    PubMed

    Guo, Luyan; Chen, Shuqin; Jiang, Hongye; Huang, Jiaming; Jin, Wenyan; Yao, Shuzhong

    2014-01-01

    There is increasing evidence suggesting that S100P has a significant role in cancer, and is associated with poor clinical outcomes. The expression of S100P mRNA and protein in endometrial cancer and normal endometrium tissues was detected by real-time quantitative RT-PCR and immunohistochemistry. Moreover, we reduced the expression of S100P in HEC-1A and Ishikawa endometrial cancer cell lines by siRNA transfection. Based on the reduced S100P mRNA expression, we measured the effects of S100P on cellular proliferation by the cell-counting kit-8. Nuclear β-catenin protein level was detected by western blotting. Cyclin D1 and c-myc mRNA expression regulated by β-catenin was detected by real-time quantitative RT-PCR. We found that the expression of S100P mRNA and protein increased in endometrial cancer tissues compared with the normal endometrium. Local S100P expression progressively increased from pathologic differenciation grade 1 to 3. After reducing the S100P expression, the cellular proliferation ability, nuclear β-catenin protein level, cyclin D1 and c-myc mRNA levels reduced. It indicated that S100P could promote cell proliferation by increasing nuclear translocation of β-catenin. The expression of S100P mRNA and protein in endometrial cancer significantly increased and is associated with pathologic differenciation grade. S100P may promote endometrial cell proliferation by increasing nuclear translocation of β-catenin.

  10. A murine uterine transcriptome, responsive to steroid receptor coactivator-2, reveals transcription factor 23 as essential for decidualization of human endometrial stromal cells.

    PubMed

    Kommagani, Ramakrishna; Szwarc, Maria M; Kovanci, Ertug; Creighton, Chad J; O'Malley, Bert W; Demayo, Francesco J; Lydon, John P

    2014-04-01

    Recent data from human and mouse studies strongly support an indispensable role for steroid receptor coactivator-2 (SRC-2)-a member of the p160/SRC family of coregulators-in progesterone-dependent endometrial stromal cell decidualization, an essential cellular transformation process that regulates invasion of the developing embryo into the maternal compartment. To identify the key progesterone-induced transcriptional changes that are dependent on SRC-2 and required for endometrial decidualization, we performed comparative genome-wide transcriptional profiling of endometrial tissue RNA from ovariectomized SRC-2(flox/flox) (SRC-2(f/f) [control]) and PR(cre/+)/SRC-2(flox/flox) (SRC-2(d/d) [SRC-2-depleted]) mice, acutely treated with vehicle or progesterone. Although data mining revealed that only a small subset of the total progesterone-dependent transcriptional changes is dependent on SRC-2 (∼13%), key genes previously reported to mediate progesterone-driven endometrial stromal cell decidualization are present within this subset. Along with providing a more detailed molecular portrait of the decidual transcriptional program governed by SRC-2, the degree of functional diversity of these progesterone mediators underscores the pleiotropic regulatory role of SRC-2 in this tissue. To showcase the utility of this powerful informational resource to uncover novel signaling paradigms, we stratified the total SRC-2-dependent subset of progesterone-induced transcriptional changes in terms of novel gene expression and identified transcription factor 23 (Tcf23), a basic-helix-loop-helix transcription factor, as a new progesterone-induced target gene that requires SRC-2 for full induction. Importantly, using primary human endometrial stromal cells in culture, we demonstrate that TCF23 function is essential for progesterone-dependent decidualization, providing crucial translational support for this transcription factor as a new decidual mediator of progesterone action.

  11. Nuclear receptor co-regulator Kruppel-like factor 9 and prohibitin 2 expression in estrogen-induced epithelial cell proliferation in the mouse uterus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Estrogen, acting through its cognate receptor estrogen receptor-' (ESR1), is a critical regulator of uterine endometrial epithelial proliferation. Although the dynamic communication between endometrial stromal (ST) and epithelial cells is considered to be an important component in this process, key ...

  12. Teacher-Student Dialogue: Transforming Teacher Interpersonal Behaviour and Pedagogical Praxis through Co-Teaching and Co-Generative Dialogue

    ERIC Educational Resources Information Center

    Rahmawati, Yuli; Koul, Rekha; Fisher, Darrell

    2015-01-01

    The paper reports a study of the effectiveness of co-teaching and co-generative dialogue in science learning and teaching in lower secondary science classes. The idea of co-teaching and co-generative dialogue--first proposed by two leading educationists, Roth and Tobin, in early 2000--made an international impact in educational research. In the…

  13. AdaRTE: adaptable dialogue architecture and runtime engine. A new architecture for health-care dialogue systems.

    PubMed

    Rojas-Barahona, L M; Giorgino, T

    2007-01-01

    Spoken dialogue systems have been increasingly employed to provide ubiquitous automated access via telephone to information and services for the non-Internet-connected public. In the health care context, dialogue systems have been successfully applied. Nevertheless, speech-based technology is not easy to implement because it requires a considerable development investment. The advent of VoiceXML for voice applications contributed to reduce the proliferation of incompatible dialogue interpreters, but introduced new complexity. As a response to these issues, we designed an architecture for dialogue representation and interpretation, AdaRTE, which allows developers to layout dialogue interactions through a high level formalism that offers both declarative and procedural features. AdaRTE aim is to provide a ground for deploying complex and adaptable dialogues whilst allows the experimentation and incremental adoption of innovative speech technologies. It provides the dynamic behavior of Augmented Transition Networks and enables the generation of different backends formats such as VoiceXML. It is especially targeted to the health care context, where a framework for easy dialogue deployment could reduce the barrier for a more widespread adoption of dialogue systems.

  14. The Use of the Dialogue Concepts from the Arsenal of the Norwegian Dialogue Pedagogy in the Time of Postmodernism

    ERIC Educational Resources Information Center

    Gradovski, Mikhail

    2012-01-01

    Inspired by the views by the American educationalist Henry Giroux on the role teachers and educationalists should be playing in the time of postmodernism and by Abraham Maslow's concept of biological idiosyncrasy, the author discusses how the concepts of the dialogues created by the representatives of Norwegian Dialogue Pedagogy, Hans Skjervheim,…

  15. High Glucose-Mediated STAT3 Activation in Endometrial Cancer Is Inhibited by Metformin: Therapeutic Implications for Endometrial Cancer

    PubMed Central

    Wallbillich, John J.; Josyula, Srirama; Saini, Uksha; Zingarelli, Roman A.; Dorayappan, Kalpana Deepa Priya; Riley, Maria K.; Wanner, Ross A.; Cohn, David E.; Selvendiran, Karuppaiyah

    2017-01-01

    Objectives STAT3 is over-expressed in endometrial cancer, and diabetes is a risk factor for the development of type 1 endometrial cancer. We therefore investigated whether glucose concentrations influence STAT3 expression in type 1 endometrial cancer, and whether such STAT3 expression might be inhibited by metformin. Methods In Ishikawa (grade 1) endometrial cancer cells subjected to media with low, normal, or high concentrations of glucose, expression of STAT3 and its target proteins was evaluated by real-time quantitative PCR (qPCR). Ishikawa cells were treated with metformin and assessed with cell proliferation, survival, migration, and ubiquitin assays, as well as Western blot and qPCR. Expression of apoptosis proteins was evaluated with Western blot in Ishikawa cells transfected with a STAT3 overexpression plasmid and treated with metformin. A xenograft tumor model was used for studying the in vivo efficacy of metformin. Results Expression of STAT3 and its target proteins was increased in Ishikawa cells cultured in high glucose media. In vitro, metformin inhibited cell proliferation, survival and migration but induced apoptosis. Metformin reduced expression levels of pSTAT3 ser727, total STAT3, and its associated cell survival and anti-apoptotic proteins. Additionally, metformin treatment was associated with increased degradation of pSTAT3 ser727. No change in apoptotic protein expression was noticed with STAT3 overexpression in Ishikawa cells. In vivo, metformin treatment led to a decrease in tumor weight as well as reductions of STAT3, pSTAT3 ser727, its target proteins. Conclusions These results suggest that STAT3 expression in type 1 endometrial cancer is stimulated by a high glucose environment and inhibited by metformin. PMID:28114390

  16. Potential hazards to embryo implantation: A human endometrial in vitro model to identify unwanted antigestagenic actions of chemicals

    SciTech Connect

    Fischer, L.; Deppert, W.R.; Pfeifer, D.; Stanzel, S.; Weimer, M.; Hanjalic-Beck, A.; Stein, A.; Straßer, M.; Zahradnik, H.P.; Schaefer, W.R.

    2012-05-01

    Embryo implantation is a crucial step in human reproduction and depends on the timely development of a receptive endometrium. The human endometrium is unique among adult tissues due to its dynamic alterations during each menstrual cycle. It hosts the implantation process which is governed by progesterone, whereas 17β-estradiol regulates the preceding proliferation of the endometrium. The receptors for both steroids are targets for drugs and endocrine disrupting chemicals. Chemicals with unwanted antigestagenic actions are potentially hazardous to embryo implantation since many pharmaceutical antiprogestins adversely affect endometrial receptivity. This risk can be addressed by human tissue-specific in vitro assays. As working basis we compiled data on chemicals interacting with the PR. In our experimental work, we developed a flexible in vitro model based on human endometrial Ishikawa cells. Effects of antiprogestin compounds on pre-selected target genes were characterized by sigmoidal concentration–response curves obtained by RT-qPCR. The estrogen sulfotransferase (SULT1E1) was identified as the most responsive target gene by microarray analysis. The agonistic effect of progesterone on SULT1E1 mRNA was concentration-dependently antagonized by RU486 (mifepristone) and ZK137316 and, with lower potency, by 4-nonylphenol, bisphenol A and apigenin. The negative control methyl acetoacetate showed no effect. The effects of progesterone and RU486 were confirmed on the protein level by Western blotting. We demonstrated proof of principle that our Ishikawa model is suitable to study quantitatively effects of antiprogestin-like chemicals on endometrial target genes in comparison to pharmaceutical reference compounds. This test is useful for hazard identification and may contribute to reduce animal studies. -- Highlights: ► We compare progesterone receptor-mediated endometrial effects of chemicals and drugs. ► 4-Nonylphenol, bisphenol A and apigenin exert weak

  17. Transcriptome analysis of endometrial tissues following GnRH agonist treatment in a mouse adenomyosis model

    PubMed Central

    Guo, Song; Lu, Xiaowei; Gu, Ruihuan; Zhang, Di; Sun, Yijuan; Feng, Yun

    2017-01-01

    Purpose Adenomyosis is a common, benign gynecological condition of the female reproductive tract characterized by heavy menstrual bleeding and dysmenorrhea. Gonadotropin-releasing hormone (GnRH) agonists are one of the medications used in adenomyosis treatment; however, their underlying mechanisms are poorly understood. Moreover, it is difficult to obtain endometrial samples from women undergoing such treatment. To overcome this, we generated an adenomyosis mouse model, which we treated with an GnRH agonist to determine its effect on pregnancy outcomes. We also analyzed endometrial gene expression following GnRH agonist treatment to determine the mechanisms that may affect pregnancy outcome in individuals with adenomyosis. Methods Neonatal female mice were divided into a control group, an untreated adenomyosis group, and an adenomyosis group treated with a GnRH agonist (n=6 each). The pregnancy outcome was observed and compared among the groups. Then, three randomly chosen transcriptomes from endometrial tissues from day 4 of pregnancy were analyzed between the adenomyosis group and the GnRH agonist treatment group by RNA sequencing and quantitative reverse transcription polymerase chain reaction (PCR). Results The litter size was significantly smaller in the adenomyosis group than in the control group (7±0.28 vs 11±0.26; P<0.05). However, the average live litter size was increased (10±0.28 vs 7±0.28; P<0.05) after GnRH agonist treatment. Three hundred and fifty-nine genes were differentially expressed in the GnRH agonist-treated group compared with the untreated group (218 were downregulated and 141 were upregulated). Differentially expressed genes were related to diverse biological processes, including estrogen metabolism, cell cycle, and metabolite biosynthesis. Conclusion GnRH agonist treatment appears to improve the pregnancy outcome of adenomyosis in a mouse model. Besides pituitary down-regulation, other possible mechanisms such as the regulation of cell

  18. Transvaginal ultrasonography and hysteroscopy as predictors of endometrial polyps in postmenopause.

    PubMed

    de Godoy Borges, Pítia Cárita; Dias, Rogério; Bonassi Machado, Rogério; Borges, João Bosco Ramos; Spadoto Dias, Daniel

    2015-01-01

    The study compared ultrasound and ambulatorial hysteroscopy as diagnostic methods detecting endometrial polyps in postmenopause women. 281 women aged 41-82 years who underwent ambulatorial hysteroscopy were analyzed for presence of uterine bleeding and/or altered transvaginal ultrasound (endometrial thickness ≥5 mm). Ultrasonography detected endometrial polyps in 22.8% of patients and endometrial thickening in the other 59.8%. Hysteroscopy diagnosed endometrial polyps in 80.8%. Ultrasonography showed sensitivity of 88.7%, specificity of 25.4%, positive predictive value of 81.7%, negative predictive value of 37.5% and accuracy of 75.4% in diagnosing endometrial polyps. Hysteroscopy showed 96.4% sensitivity, 74.6% specificity, 93.4% positive predictive value, 84.6% negative predictive value and 91.8% accuracy. Hysteroscopy demonstrated more accuracy than ultrasonography, which is not sufficient for accurate diagnosis.

  19. Differential Expression and Clinical Significance of DNA Methyltransferase 3B (DNMT3B), Phosphatase and Tensin Homolog (PTEN) and Human MutL Homologs 1 (hMLH1) in Endometrial Carcinomas

    PubMed Central

    Li, Wenting; Wang, Ying; Fang, Xinzhi; Zhou, Mei; Li, Yiqun; Dong, Ying; Wang, Ruozheng

    2017-01-01

    Background The aim of this study was to investigate the expression and the clinicopathologic significance of DNA methyltransferase 3B (DNMT3B), phosphatase and tensin homolog (PTEN) and human MutL homologs 1 (hMLH1) in endometrial carcinomas between Han and Uygur women in Xinjiang. Material/Methods The expression of DNMT3B, PTEN, and hMLH1 in endometrial carcinomas were assessed by immunohistochemistry, followed by an analysis of their relationship to clinical-pathological features and prognosis. Results There were a 61.7% (95/154) overexpression of DNMT3B, 50.0% (77/154) loss of PTEN expression and 18.2% (28/154) loss of hMLH1 expression. The expression of DNMT3B and PTEN in endometrial carcinomas was statistically significantly different between Uygur women and Han women (p=0.001, p=0.010, respectively). DNMT3B expression was statistically significant based on the grade of endometrial carcinomas (p=0.031). PTEN loss was statistically significant between endometrioid carcinomas (ECs) and non endometrioid carcinomas (NECs) (p=0.040). DNMT3B expression was statistically significant in different myometrial invasion groups in Uygur women (p=0.010). Furthermore, the correlation of DNMT3B and PTEN expression was significant in endometrial carcinomas (p=0.021). PTEN expression was statistically significant in the overall survival (OS) rate of women with endometrial cancers (p=0.041). Conclusions Our findings suggest that PTEN and DNMT3B possess common regulation features as well as certain ethnic differences in expression between Han women and Uygur women. An interaction may exist in the pathogenesis of endometrial carcinoma. DNMT3B was expressed differently in cases of myometrial invasion and PTEN was associated with OS, which suggested that these molecular markers may be useful in the evaluation of the biological behavior of endometrial carcinomas and may be useful indicators of prognosis in women with endometrial carcinomas. PMID:28220037

  20. Exploring classroom life through cogenerative dialogues

    NASA Astrophysics Data System (ADS)

    Higgins, Joanna; Bonne, Linda

    2014-03-01

    In response to Shady's reflection on his experience as a teacher-researcher in which he explored different cogen structures, we consider fluid participant configurations using cogens as a research method to provide insights into classroom life. Our cogens illuminated the role of symbolic, cultural and social capital in student-teacher alignments that changed across different classroom situations. In Shady's study, as well as our own, respectful student-teacher relationships that involved the teacher and students first establishing common social capital, enabled the teacher to "be in with" the students, and vice versa. We raise questions about how the structure of cogens might affect the nature of the dialogue that is cogenerated.

  1. Interpretive research methodology: broadening the dialogue.

    PubMed

    Lowenberg, J S

    1993-12-01

    This article expands the dialogue on interpretive research methodology, locating this set of approaches within a broad historical and interdisciplinary context. Several of the most commonly held misconceptions in nursing, particularly those related to the meanings and derivations ascribed to "grounded theory," "symbolic interactionism," and "ethnography," are examined. The interpretive research approaches not only have gained broader acceptance across disciplines, but also have shifted in more radical and often less structured directions during the past decade. Several pivotal areas of these ongoing shifts are analyzed for their relevance to nursing research: the influence of critical and feminist theory and postmodernism, the ambiguity inherent in both every-day life and the research enterprise, the importance of locating the researcher, power and status inequities, the problematic aspects of language, meaning, and representation, and the emphasis on reflexivity and context as constitutive of meaning.

  2. [Knowledge production: a dialogue among different knowledge].

    PubMed

    Erdmann, Alacoque Lorenzini; Schlindwein, Betina Hömer; de Sousa, Francisca Georgina Macedo

    2006-01-01

    This text approaches the necessary dialogue among different knowledge and considers the advances within Nursing in the search for consistence and clarity within the Nursing discipline. Towards this end, the text is based upon transdisciplinarity, intersectorality, complexity, and the interaction of different pairs in health and other areas, as well as the sustainance of scientific and technological space within Nursing. It argues perspectives that open possibilities for scientific and technological knowledge construction within a more responsible and mutual social commitment. The purpose of the paperis to amplify the aptitude for contextualization and globalize different knowledge, as well as transcend differences and peculiarities within the perspective of more qualitative policies which may overcome disciplinary barriers.

  3. [Literature, history and pharmacy: a possible dialogue].

    PubMed

    Rezende, Irene Nogueira de

    2015-01-01

    In the Memory Center of the Pharmacy School of UFMG there are documents relating to the passage of Carlos Drummond de Andrade through the institution, a fact that has led to reflection on the presence of the pharmacy and the pharmaceutical expert in literature. By means of interdisciplinary dialogue and research into elements that prove this presence, active participation and presence in the literature, an attempt was made to historicize these ties, not only of the poet from Itabira, but other men of letters, be they pharmaceutical professionals or people inspired by them. The objective was also to highlight some evidence that supports and demonstrates the importance of this professional in Brazilian society of the late-nineteenth century and early-twentieth century.

  4. Dasatinib in Treating Patients With Recurrent or Persistent Ovarian, Fallopian Tube, Endometrial or Peritoneal Cancer

    ClinicalTrials.gov

    2017-04-05

    Endometrial Clear Cell Adenocarcinoma; Estrogen Receptor Negative; Ovarian Clear Cell Cystadenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Recurrent Uterine Corpus Carcinoma

  5. Endometrial Tuberculosis Simulating an Ovarian Cancer: a case report.

    PubMed

    Di Giovanni, Silvia Eleonora; Cunha, Teresa Margarida; Duarte, Ana Luisa; Alves, Ines

    2016-06-01

    Female genital tuberculosis remains a major health problem in developing countries and is an important cause of infertility. As symptoms, laboratory data and physical findings are non-specific, its diagnosis can be difficult. We describe a case of a 39-year-old woman suffering from peri-umbilical pain and increased abdominal size for one year, anorexia, asthenia, weight loss, occasionally dysuria and dyspareunia, and four months amenorrhea. Laboratory data revealed cancer antigen 125 (CA-125) level of 132.3 U/mL, erythrocyte sedimentation rate of 42 mm/h, and gamma-globulins of 2.66 g/dL. Computed tomography scan showed loculated ascites. It was initially suspected a carcinomatous origin, but ascites evaluation was negative for malignant cells. Magnetic resonance imaging from another hospital showed endometrial heterogeneity. Therefore, an endometrial biopsy was performed demonstrating an inflammatory infiltrate with giant cells of type Langhans and bacteriological culture identified Mycobacterium tuberculosis.

  6. Isolation and characterization of the pig endometrial arylsulphatase A.

    PubMed Central

    Rahi, H; Srivastava, P N

    1983-01-01

    The pig endometrial arylsulphatase A was purified 3322-fold to a specific activity of 150 mumol/min per mg. The purification involved (NH4)2SO4 fractionation, chromatography on concanavalin A-Sepharose and DEAE-Sepharose, gel filtrations on Sephadex G-200 at pH 7.4 and 5, and a new preparative gel-electrophoresis technique. The homogeneous enzyme is a glycoprotein containing 20% carbohydrate. The purified enzyme has Mr about 120 000 and it contains subunits of Mr 63 000. The pig endometrial arylsulphatase A shows many properties in common with those of arylsulphatases A purified from other sources. The similarities include their low isoelectric points, the anomalous time-activity relationships, multi-pH optima, inhibition by SO3(2-), SO4(2-), phosphate ions, metal ions and nucleoside phosphates, pH- and ionic-strength-dependent polymerization and amino acid composition. PMID:6136269

  7. Current Issues in the Diagnosis and Treatment of Endometrial Carcinoma

    PubMed Central

    Stubert, J.; Gerber, B.

    2016-01-01

    Endometrial carcinoma is the most common carcinoma of the female genital tract. Its most important clinical sign is postmenopausal bleeding. An endometrial biopsy is essential for diagnosis. Treatment decisions are governed by tumour risk assessment and patient comorbidity, which is often present. Pelvic and paraaortic lymph node dissection is unnecessary in low risk cases (definition: pT1 a, G1/2) and adjuvant radiotherapy and systemic treatments are usually avoidable. Treatment of high-risk patients (G3 and/or pT1b) and palliative cases is difficult and not well standardised. New molecular-based subtype classification may help treatment decision making in future. PMID:26941450

  8. 75 FR 39935 - Drinking Water Strategy Contaminants as Group(s)-Notice of Web Dialogue

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-13

    ... AGENCY RIN 2040-AD94 Drinking Water Strategy Contaminants as Group(s)--Notice of Web Dialogue AGENCY... Web dialogue. The discussion topics for this Web dialogue are focused on the first of the four... group(s). DATES: The Web dialogue is a two-day event. It will open at 9 a.m., Eastern Daylight Time (6...

  9. Menstrual physiology: implications for endometrial pathology and beyond

    PubMed Central

    Maybin, Jacqueline A.; Critchley, Hilary O.D.

    2015-01-01

    BACKGROUND Each month the endometrium becomes inflamed, and the luminal portion is shed during menstruation. The subsequent repair is remarkable, allowing implantation to occur if fertilization takes place. Aberrations in menstrual physiology can lead to common gynaecological conditions, such as heavy or prolonged bleeding. Increased knowledge of the processes involved in menstrual physiology may also have translational benefits at other tissue sites. METHODS Pubmed and Cochrane databases were searched for all original and review articles published in English until April 2015. Search terms included ‘endometrium’, ‘menstruation’, ‘endometrial repair’, ‘endometrial regeneration’ ‘angiogenesis’, ‘inflammation’ and ‘heavy menstrual bleeding’ or ‘menorrhagia’. RESULTS Menstruation occurs naturally in very few species. Human menstruation is thought to occur as a consequence of preimplantation decidualization, conferring embryo selectivity and the ability to adapt to optimize function. We highlight how current and future study of endometrial inflammation, vascular changes and repair/regeneration will allow us to identify new therapeutic targets for common gynaecological disorders. In addition, we describe how increased knowledge of this endometrial physiology will have many translational applications at other tissue sites. We highlight the clinical applications of what we know, the key questions that remain and the scientific and medical possibilities for the future. CONCLUSIONS The study of menstruation, in both normal and abnormal scenarios, is essential for the production of novel, acceptable medical treatments for common gynaecological complaints. Furthermore, collaboration and communication with specialists in other fields could significantly advance the therapeutic potential of this dynamic tissue. PMID:26253932

  10. Endometrial cancer following radiation therapy for cervical cancer

    SciTech Connect

    Gallion, H.H.; van Nagell, J.R. Jr.; Donaldson, E.S.; Powell, D.E.

    1987-05-01

    The clinical and histologic features of eight cases of carcinoma of the endometrium which developed following radiation therapy for squamous cell carcinoma of the cervix are described. No patient had a well-differentiated tumor and significant myometrial invasion was present in all cases. Three of the eight tumors were papillary serous adenocarcinoma. Five of the eight patients developed recurrent tumor and died of their disease. The risk of endometrial cancer in patients previously radiated for cervical cancer is evaluated.

  11. The role of robotic surgery in endometrial cancer.

    PubMed

    O'Malley, David M; Smith, Blair; Fowler, Jeffrey M

    2015-12-01

    Robotic surgery for endometrial cancer has less blood loss, shorter hospital stays, and less postoperative complications compared to laparotomies. Robotic technologic advantages over laparoscopic technique are most pronounced in obese patients. The shorter learning curve may explain the greater utilization of the robotic technique. Robotic surgery will continue as a mainstay in the treatment of uterine cancers as we become more efficient and cost conscious while maintaining the high quality outcomes that have been reported.

  12. Intergroup dialogue courses on sexual orientation: lesbian, gay and bisexual student experiences and outcomes.

    PubMed

    Dessel, Adrienne B; Woodford, Michael R; Warren, Naomi

    2011-01-01

    Intergroup dialogue is a method of social justice education. Most intergroup dialogue research explores race and gender identities. Sexual orientation dialogues are uncommon and not yet examined empirically. This qualitative study explores sexual orientation dialogue courses from the perspective of lesbian, gay, and bisexual (LGB) student participants. Understanding target, or marginalized, group perspective of planned intergroup experiences is important given concerns raised in the literature. We document student motivations for participating in dialogues, core outcomes, and main challenges that arose in dialogue. Core outcomes include learning about and accepting one's sexual identity and empowerment. Challenges include those stemming from invisibility of sexual orientation identity. Recommendations are made for intergroup dialogue practice and research.

  13. Pancreatic endometrial cyst mimics mucinous cystic neoplasm of the pancreas

    PubMed Central

    Mederos, Michael A; Villafañe, Nicole; Dhingra, Sadhna; Farinas, Carlos; McElhany, Amy; Fisher, William E; Van Buren II, George

    2017-01-01

    Pancreatic cysts include a variety of benign, premalignant, and malignant lesions. Endometrial cysts in the pancreas are exceedingly rare lesions that are difficult to diagnose pre-operatively. This report describes the findings in a 43-year-old patient with a recent episode of acute pancreatitis who presented with a large cyst in the tail of the pancreas. Imaging demonstrated a loculated pancreatic cyst, and cyst fluid aspiration revealed an elevated amylase and carcinoembryonic antigen. The patient experienced an interval worsening of abdominal pain, fatigue, diarrhea, and a 15-pound weight loss 3 mo after the initial episode of pancreatitis. With concern for a possible pre-malignant lesion, the patient underwent a laparoscopic distal pancreatectomy with splenectomy, which revealed a 16 cm × 12 cm × 4 cm lesion. Final histopathology was consistent with an intra-pancreatic endometrial cyst. Here we discuss the overlapping imaging and laboratory features of pancreatic endometrial cysts and mucinous cystic neoplasms of the pancreas. PMID:28246486

  14. Independent prognostic value of peritoneal immunocytodiagnosis in endometrial carcinoma.

    PubMed

    Benevolo, M; Mariani, L; Vocaturo, G; Vasselli, S; Natali, P G; Mottolese, M

    2000-02-01

    Among the clinical parameters that play a pivotal role in predicting the outcome of patients with endometrial carcinoma, intraperitoneal microscopic dissemination represents an important cause of recurrences. To date, peritoneal cytology has been incorporated into the current surgical staging system (International Federation of Gynecology and Obstetrics 88), although its predictive value remains a controversial issue. In this study the authors investigated the possibility of applying immunocytochemistry (ICC) to the diagnosis of peritoneal washing (PW) aimed at improving conventional cytology and verifying the prognostic value of peritoneal malignant cells. The authors analyzed 182 PWs sampled from endometrial cancer patients. The ICC analysis was performed using two monoclonal antibodies (MAbs)--AR-3 and B72.3--that in combination recognize more than 95% of endometrial carcinomas. The presence of peritoneal-free cancer cells was identified morphologically in 27 of 182 lavages (14.8%) and ICC in 50 of 182 (27.5%), with a significant improvement (p <0.0001). Five-year survival analysis, comparing results of ICC and cytodiagnosis, demonstrated a significant decrease of disease-free survival in patients with peritoneal microscopic disease. Furthermore, multivariate analysis showed that ICC diagnosis of PWs is an independent prognostic factor. Data indicate that the use of selected MAbs allows one to identify cytologically false-negative cases, providing results that are highly predictive of a worse clinical outcome.

  15. Pseudo-placentational endometrial cysts in a bitch.

    PubMed

    Bartel, C; Schönkypl, S; Walter, I

    2010-02-01

    Cystic alterations of the canine endometrium compromise reproduction and fertility of the bitch and may lead to life-threatening diseases, such as pyometra. Even without clinical evidence, reduction of the uterine lumen by cysts implicates disturbances during migration, nidation and development of the embryo. Several studies point to the high variability of morphology of uterine endometrial cysts but they lack detailed analyses of alterations. In the present study, immunohistochemistry was used to investigate the expression of steroid hormone receptors (oestrogen, progesterone), proliferation activity, inflammation and infection in the cystic affected tissue regions in contrast to the normal endometrium. Oestrogen receptor expression showed a high density of receptors throughout the surface epithelial cells, crypt epithelial cells, glandular epithelial cells and stromal cells of the normal endometrium as well as the cystic affected regions. Proliferation in the cysts was verified in the middle and basal cells of the crypts. Neither in the endometrium nor in the cysts inflammatory processes or evidence of infection could be detected. Furthermore, lectin histochemistry and electron microscopic methods showed that lectin binding patterns and cell morphology of internal epithelial lining and surface epithelium of the cysts can be used to characterize and distinguish different types of cystic alterations. Analogies between epithelial cells of the glandular chambers of the canine placenta and the cystic cellular morphology, steroid hormone receptor distribution as well as lectin binding patterns of the endometrial cysts, as observed in this study, suggest to introduce the term 'pseudo-placentational endometrial cysts'.

  16. Supporting patients following pelvic radiotherapy for endometrial cancer.

    PubMed

    Elliot, Emma

    Endometrial cancer is the commonest gynaecological cancer in the UK. Affected women often live with long-term complex and debilitating side-effects of radiotherapy treatment, such as bowel toxicity, fatigue and psychosexual problems. Women also experience negative feelings around self-image and sexuality, which contribute to a decline in their quality of life. A review of the literature and national policy showed that women had unmet needs after completing radiotherapy treatment for endometrial cancers, and that cancer nurse specialists are in a prime position to deliver a holistic package of personalized care. Staff at a nurse-led gynaecology oncology clinic performed an audit that found the clinic was not meeting the longer-term needs of most women after radiotherapy for endometrial cancers, and that women were attending multiple appointments to access different services. The clinical nurse specialist reviewed local and national policy, carried out situational analysis and engaged with service users to identify where change was needed and to examine whether a new model of service provision, where patients could consult different professionals at one appointment, would help the move forward in life after treatment.

  17. The complementary deoxyribonucleic acid sequence of guinea pig endometrial prorelaxin.

    PubMed

    Lee, Y A; Bryant-Greenwood, G D; Mandel, M; Greenwood, F C

    1992-03-01

    The nucleotide sequence of the relaxin gene transcript in the endometrium of the late pregnant guinea pig has been determined. The strategy used was a combination of polymerase chain reaction (PCR) with primers designed from the mRNA sequence of porcine preprorelaxin, rapid amplification of cDNA ends-PCR, and blunt end cloning in M13 mp18. With heterologous primers, a 226-basepair (bp) segment of the guinea pig relaxin gene sequence was obtained and was used to design a guinea pig-specific primer for use with the rapid amplification of cDNA ends-PCR method. The latter allowed completion of the sequence of 336 bp, with a 96-bp overlap. The sequence obtained shows greater homology at both the nucleotide and amino acid levels with porcine and human relaxins H1 and H2 than with rat relaxin, supporting the thesis that the guinea pig is not a rodent. The transcription of the guinea pig endometrial relaxin gene during pregnancy was confirmed by Northern analysis of guinea pig endometrial tissues with a species-specific cDNA probe. The endometrial relaxin gene is transcribed during pregnancy, but not in lactation, consistent with the observed immunostaining for relaxin.

  18. The effect of tumor necrosis factor α (TNFα), interleukin 1β (IL1β) and interleukin 6 (IL6) on endometrial PGF2α synthesis, metabolism and release in early-pregnant pigs.

    PubMed

    Franczak, A; Zmijewska, A; Kurowicka, B; Wojciechowicz, B; Petroff, B K; Kotwica, G

    2012-01-01

    Cytokines produced by the porcine uterus and embryos may be involved in the regulation of endometrial prostaglandin synthesis, metabolism, and release. We studied the effect of tumor necrosis factor α (TNFα), interleukin 1β (IL1β) and interleukin 6 (IL6) on: 1) endometrial release of prostaglandin F2α (PGF2α), 2) expression of the terminal enzyme of PGF2α synthesis--PGF synthase mRNA (PGFS mRNA), 3) secretion of PGF(2)α metabolite--13,14-dihydro-15-keto PGF2α (PGFM) by the endometrium and 4) presence and activity of endometrial NAD-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH). The effects of cytokines were determined on days 10-11 and days 12-13, e.g., before and during maternal recognition of pregnancy, and on days 15-16, e.g., during the peri-implantation period and compared with its effect in cyclic gilts on corresponding days of the estrous cycle. TNFα did not affect endometrial release of PGF2α in pregnant and cyclic pigs. IL1β enhanced endometrial PGF2α release on days 12-13 and 15-16 in pregnant and cyclic pigs, respectively. IL6 increased PGF2α release mainly on days 15-16 of pregnancy. Expression of PGFS mRNA was decreased by IL1β on days 12-13 of pregnancy (P<0.05) and increased in response to IL1β, TNFα and IL6 on 12-13 (P<0.05) and 15-16 (P<0.01) of the estrous cycle. IL1β increased release of PGFM in gravid pigs on days 12-13, 15-16 and in non-gravid pigs 10-11 and 15-16 of the cycle. On days 15-16 of pregnancy TNFα and IL6 increased endometrial secretion of PGFM. We determined that in porcine endometrium NAD-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is present. In gravid pigs, the highest expression of endometrial 15-PGDH occurred during days 12-13 of pregnancy, while in non-gravid pigs during days 10-11 of the estrous cycle. These data provide new evidence that TNFα, IL1β, IL6 are involved in the regulation of endometrial synthesis, release and metabolism of PGF2α to protect CL during early pregnancy

  19. Common genetic variation within IGFI, IGFII, IGFBP-1, and IGFBP-3 and endometrial cancer risk

    PubMed Central

    McGrath, Monica; Lee, I-Min; Buring, Julie; De Vivo, Immaculata

    2011-01-01

    Objective The insulin-like growth factor (IGF) pathway plays a critical role in the growth and development of the uterus and is believed to function as a mediator of steroid hormone actions in the endometrium. The local expression of genes encoding IGFs and IGF-binding proteins (IGFBPs) are important in determining IGF bioactivity in the uterus. Genetic variation in key genes within the IGF pathway may influence the rate of cellular proliferation and differentiation in the uterus and ultimately affect the risk of endometrial cancer. Our hypothesis is that variant alleles in key genes involved in the IGF pathway will influence the development of endometrial cancer. Methods We conducted a case-control study nested within the Nurses’ Health Study (NHS) and the Women's Health Study (WHS) to investigate the association between forty-four polymorphisms within IGFI, IGFII, IGFBP-1, and IGFBP-3 with endometrial cancer risk using 692 invasive endometrial cancer cases and 1723 matched controls. We used conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) to assess the risk of endometrial cancer. Results We observed an inverse association with IGFII rs3741211 and endometrial cancer risk (OR = 0.79 (95% CI: 0.63, 0.99)) and IGFII rs1004446 and endometrial cancer risk (OR = 0.80 (95% CI: 0.68, 0.94)). We also observed an inverse association with IGFBP-3 rs2453839 and endometrial cancer risk (OR= 0.81 (95%CI: 0.67, 0.98). However, we did not observe any statistically significant associations with the polymorphisms in IGFI and IGFBP1 and endometrial cancer risk. Conclusions Genetic variation with IGFII and IGFBP-3 may influence endometrial cancer risk in Caucasians. Polymorphisms in IGFI and IGFBP-1 were not associated with endometrial cancer risk, but further research is needed. PMID:21078522

  20. The Buber-Rogers Dialogue: Theory Confirmed in Experience

    ERIC Educational Resources Information Center

    Seckinger, Donald S.

    1976-01-01

    Considers a dialogue between Carl Rogers and Martin Buber and its use both in distinguishing the concept teaching from the concept therapy as a general case and specifically in differentiating existential psychotherapy from Buber's theory of instruction. (Author/RK)

  1. Science and religion in dialogue over the global commons

    NASA Astrophysics Data System (ADS)

    Edenhofer, Ottmar; Flachsland, Christian; Knopf, Brigitte

    2015-10-01

    The Pope's encyclical makes unprecedented progress in developing scientific dialogue with religion by drawing on research, and encouraging further discussion about the ethical challenge of governing the global commons.

  2. Dialogue-Writing in the Teaching of Composition.

    ERIC Educational Resources Information Center

    Haymon, Theresa Drew

    1979-01-01

    Argues for the use of dialogue writing as an aid in the teaching of composition. Notes among its advantages its potential for addressing a number of specific writing problems rarely eliminated by drill work or class lectures. (FL)

  3. Using "Dialogue" Labs in a Community-College Physics Course.

    ERIC Educational Resources Information Center

    Uretsky, Jack L.

    1993-01-01

    Describes a community-college curriculum that incorporates Socratic Dialogue Inducing (SDI) laboratories into a new calculus-based preengineering physics sequence. SDI allows for group discussion labs that emphasize the concepts being taught in the lectures. (ZWH)

  4. Shaping the Public Dialogue on Climate Change

    NASA Astrophysics Data System (ADS)

    Spitzer, W.; Anderson, J. C.

    2012-12-01

    In order to broaden the public dialogue about climate change, climate scientists need to leverage the potential of informal science education and recent advances in social and cognitive science. In the US, more than 1,500 informal science venues (science centers, museums, aquariums, zoos, nature centers, national parks, etc.) are visited annually by 61% of the population. Extensive research shows that these visitors are receptive to learning about climate change and trust these institutions as reliable sources. Given that we spend less than 5% of our lifetime in a classroom, and only a fraction of that is focused on science, informal science venues will continue to play a critical role in shaping public understanding of environmental issues in the years ahead. Public understanding of climate change continues to lag far behind the scientific consensus not merely because the public lacks information, but because there is in fact too much complex and contradictory information available. Fortunately, we can now (1) build on careful empirical cognitive and social science research to understand what people already value, believe, and understand; and then (2) design and test strategies for translating complex science so that people can examine evidence, make well-informed inferences, and embrace science-based solutions. The New England Aquarium is leading a national effort to enable informal science education institutions to effectively communicate the impacts of climate change and ocean acidification on marine ecosystems. This NSF-funded partnership, the National Network for Ocean and Climate Change Interpretation (NNOCCI), involves the Association of Zoos and Aquariums, FrameWorks Institute, Woods Hole Oceanographic Institution, Monterey Bay Aquarium, and National Aquarium, with evaluation conducted by the New Knowledge Organization, Pennsylvania State University, and Ohio State University. We believe that skilled interpreters can serve as "communication strategists" by

  5. Immunohistochemical detection of P-glycoprotein in endometrial adenocarcinoma.

    PubMed Central

    Axiotis, C. A.; Monteagudo, C.; Merino, M. J.; LaPorte, N.; Neumann, R. D.

    1991-01-01

    P-glycoprotein (Pgp) has emerged as the central mediator in classic multidrug resistance in model systems in vitro. High levels of Pgp also have been detected in many normal human tissues and tumors; and its role in clinical drug resistance is currently under investigation. Recently significant levels of Pgp were localized to gravid and secretory endometrium; and it was demonstrated that the combination of estrogen and progesterone is sufficient to induce high levels of both Pgp mRNA and Pgp in uterine secretory epithelium. These findings suggest that increased Pgp expression also may be present in hormone-responsive malignancies such as endometrial adenocarcinoma. To determine whether Pgp is expressed in endometrial adenocarcinoma, 36 endometrial adenocarcinomas (grade I [n = 17]; grade II [n = 6]; grade III [n = 13]) were investigated retrospectively by the avidin-biotin-complex immunohistochemical procedure using three murine monoclonal antibodies (MAb) MAb C219, MAb C494, and MAb JSB-1, which recognize spatially distinct cytoplasmic epitopes of Pgp. Seventy-two percent of the tumors showed positive immunostaining with at least one MAb; 67% showed immunostaining with MAb C219, 50% with MAb C494, and 62% with MAb JSB-1. Forty-six percent of tumors were immunoreactive to two and 29% to all three antibodies. Membranous and Golgi/paranuclear type staining patterns were observed. Overall the intensity of immunostaining varied from one sample to another for a given tumor type, and considerable heterogeneity of expression was commonly seen within a given tumor. Strong to moderate immunoreactivity was seen in diffusely infiltrating, adenosquamous, and serous papillary carcinomas. In general, immunoreactivity to MAb C494 was weaker than MAb C219 or MAb JSB-1. Adenomatous and non-neoplastic endometrium adjacent to the tumors displayed strong membranous immunostaining with MAb JSB-1. Endometrial capillaries showed weak-to-moderate immunostaining to all three antibodies. It

  6. Teaching nursing without lecturing: critical pedagogy as communicative dialogue.

    PubMed

    Mikol, Carmella

    2005-01-01

    This article is an interpretive analysis of the author's method of teaching nursing to a diverse student body in an associate degree program. Rather than lecturing, the author and her colleagues facilitate small-group discussions, engaging students in communicative dialogue.This method leads to flexibility and openness to student ideas as well as opportunities to share personal stories and dialogue with students. As a result, students are helped to overcome misunderstanding, misconceptions, and misinterpretations of the nursing literature.

  7. Single-Photon Secure Quantum Dialogue Protocol Without Information Leakage

    NASA Astrophysics Data System (ADS)

    Zhou, Nan-Run; Hua, Tian-Xiang; Wu, Gui-Tong; He, Chao-Sheng; Zhang, Ye

    2014-11-01

    Combining the idea of ping-pong protocol with Controlled-NOT operation, we propose a secure quantum dialogue protocol based on single-photonss. Bob obtains the information of the encrypted quantum state by performing Controlled-NOT operation on the auxiliary particle and the encrypted single-photonss. Unlike the previous quantum dialogue protocols based on single-photonss, the proposed protocol not only overcomes information leakage but also possesses an acceptable efficiency.

  8. Progesterone action in endometrial cancer, endometriosis, uterine fibroids, and breast cancer.

    PubMed

    Kim, J Julie; Kurita, Takeshi; Bulun, Serdar E

    2013-02-01

    Progesterone receptor (PR) mediates the actions of the ovarian steroid progesterone, which together with estradiol regulates gonadotropin secretion, prepares the endometrium for implantation, maintains pregnancy, and differentiates breast tissue. Separation of estrogen and progesterone actions in hormone-responsive tissues remains a challenge. Pathologies of the uterus and breast, including endometrial cancer, endometriosis, uterine fibroids, and breast cancer, are highly associated with estrogen, considered to be the mitogenic factor. Emerging evidence supports distinct roles of progesterone and its influence on the pathogenesis of these diseases. Progesterone antagonizes estrogen-driven growth in the endometrium, and insufficient progesterone action strikingly increases the risk of endometrial cancer. In endometriosis, eutopic and ectopic tissues do not respond sufficiently to progesterone and are considered to be progesterone-resistant, which contributes to proliferation and survival. In uterine fibroids, progesterone promotes growth by increasing proliferation, cellular hypertrophy, and deposition of extracellular matrix. In normal mammary tissue and breast cancer, progesterone is pro-proliferative and carcinogenic. A key difference between these tissues that could explain the diverse effects of progesterone is the paracrine interactions of PR-expressing stroma and epithelium. Normal endometrium is a mucosa containing large quantities of distinct stromal cells with abundant PR, which influences epithelial cell proliferation and differentiation and protects against carcinogenic transformation. In contrast, the primary target cells of progesterone in the breast and fibroids are the mammary epithelial cells and the leiomyoma cells, which lack specifically organized stromal components with significant PR expression. This review provides a unifying perspective for the diverse effects of progesterone across human tissues and diseases.

  9. Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis.

    PubMed

    Aghajanova, L; Tatsumi, K; Horcajadas, J A; Zamah, A M; Esteban, F J; Herndon, C N; Conti, M; Giudice, L C

    2011-04-01

    Eutopic endometrium in endometriosis has molecular evidence of resistance to progesterone (P(4)) and activation of the PKA pathway in the stromal compartment. To investigate global and temporal responses of eutopic endometrium to P(4), we compared early (6-h), intermediate (48-h), and late (14-Day) transcriptomes, signaling pathways, and networks of human endometrial stromal fibroblasts (hESF) from women with endometriosis (hESF(endo)) with hESF from women without endometriosis (hESF(nonendo)). Endometrial biopsy samples were obtained from subjects with and without mild peritoneal endometriosis (n = 4 per group), and hESF were isolated and treated with P(4) (1 μM) plus estradiol (E(2)) (10 nM), E(2) alone (10 nM), or vehicle for up to 14 days. Total RNA was subjected to microarray analysis using a Gene 1.0 ST (Affymetrix) platform and analyzed by using bioinformatic algorithms, and data were validated by quantitative real-time PCR and ELISA. Results revealed unique kinetic expression of specific genes and unique pathways, distinct biological and molecular processes, and signaling pathways and networks during the early, intermediate, and late responses to P(4) in both hESF(nonendo) and hESF(endo), although a blunted response to P(4) was observed in the latter. The normal response of hESF to P(4) involves a tightly regulated kinetic cascade involving key components in the P(4) receptor and MAPK signaling pathways that results in inhibition of E(2)-mediated proliferation and eventual differentiation to the decidual phenotype, but this was not established in the hESF(endo) early response to P(4). The abnormal response of this cell type to P(4) may contribute to compromised embryonic implantation and infertility in women with endometriosis.

  10. Characterization of estrogenicity of phytoestrogens in an endometrial-derived experimental model.

    PubMed Central

    Hopert, A C; Beyer, A; Frank, K; Strunck, E; Wünsche, W; Vollmer, G

    1998-01-01

    Severe developmental and reproductive disorders in wild animals have been linked to high exposure to persistent environmental chemicals with hormonal activity. These adverse effects of environmental estrogens have raised considerable concern and have received increasing attention. Although numerous chemicals with the capacity to interfere with the estrogen receptor (ER) have been identified, information on their molecular mechanism of action and their relative potency is rather limited. For the endometrium, the lack of information is due to the lack of a suitable experimental model. We investigated the functions of phytoestrogens in an endometrial-derived model, RUCA-I rat endometrial adenocarcinoma cells. The cells were cultured on a reconstituted basement membrane to preserve their functional differentiation and estrogen responsiveness. We assessed the relative binding affinity to the estrogen receptor of the selected phytoestrogens coumestrol, genistein, daidzein, and the putative phytoestrogen mangostin compared to estradiol by a competitive Scatchard analysis. The following affinity ranking was measured: 17beta-estradiol >>> coumestrol > genistein > daidzein >>> mangostin. In addition, we investigated the capacity of these compounds to promote the increased production of complement C3, a well-known estradiol-regulated protein of the rat endometrium. All substances tested increased the production of complement C3, although different concentrations were necessary to achieve equivalent levels of induction compared to estradiol. Mechanistically we were able to demonstrate that the increase of complement C3 production was mediated by primarily increasing its steady-state mRNA level. These findings indicate that RUCA-I cells represent a sensitive model system to elucidate relative potencies and functions of environmental estrogens in an endometrium-derived model. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:9721258

  11. Progesterone Action in Endometrial Cancer, Endometriosis, Uterine Fibroids, and Breast Cancer

    PubMed Central

    Kim, J. Julie; Kurita, Takeshi

    2013-01-01

    Progesterone receptor (PR) mediates the actions of the ovarian steroid progesterone, which together with estradiol regulates gonadotropin secretion, prepares the endometrium for implantation, maintains pregnancy, and differentiates breast tissue. Separation of estrogen and progesterone actions in hormone-responsive tissues remains a challenge. Pathologies of the uterus and breast, including endometrial cancer, endometriosis, uterine fibroids, and breast cancer, are highly associated with estrogen, considered to be the mitogenic factor. Emerging evidence supports distinct roles of progesterone and its influence on the pathogenesis of these diseases. Progesterone antagonizes estrogen-driven growth in the endometrium, and insufficient progesterone action strikingly increases the risk of endometrial cancer. In endometriosis, eutopic and ectopic tissues do not respond sufficiently to progesterone and are considered to be progesterone-resistant, which contributes to proliferation and survival. In uterine fibroids, progesterone promotes growth by increasing proliferation, cellular hypertrophy, and deposition of extracellular matrix. In normal mammary tissue and breast cancer, progesterone is pro-proliferative and carcinogenic. A key difference between these tissues that could explain the diverse effects of progesterone is the paracrine interactions of PR-expressing stroma and epithelium. Normal endometrium is a mucosa containing large quantities of distinct stromal cells with abundant PR, which influences epithelial cell proliferation and differentiation and protects against carcinogenic transformation. In contrast, the primary target cells of progesterone in the breast and fibroids are the mammary epithelial cells and the leiomyoma cells, which lack specifically organized stromal components with significant PR expression. This review provides a unifying perspective for the diverse effects of progesterone across human tissues and diseases. PMID:23303565

  12. Inhibition of Histone Deacetylase Activity in Human Endometrial Stromal Cells Promotes Extracellular Matrix Remodelling and Limits Embryo Invasion

    PubMed Central

    Atkinson, Stuart P.; Quiñonero, Alicia; Martínez, Sebastián; Pellicer, Antonio; Simón, Carlos

    2012-01-01

    Invasion of the trophoblast into the maternal decidua is regulated by both the trophoectoderm and the endometrial stroma, and entails the action of tissue remodeling enzymes. Trophoblast invasion requires the action of metalloproteinases (MMPs) to degrade extracellular matrix (ECM) proteins and in turn, decidual cells express tissue inhibitors of MMPs (TIMPs). The balance between these promoting and restraining factors is a key event for the successful outcome of pregnancy. Gene expression is post-transcriptionally regulated by histone deacetylases (HDACs) that unpacks condensed chromatin activating gene expression. In this study we analyze the effect of histone acetylation on the expression of tissue remodeling enzymes and activity of human endometrial stromal cells (hESCs) related to trophoblast invasion control. Treatment of hESCs with the HDAC inhibitor trichostatin A (TSA) increased the expression of TIMP-1 and TIMP-3 while decreased MMP-2, MMP-9 and uPA and have an inhibitory effect on trophoblast invasion. Moreover, histone acetylation is detected at the promoters of TIMP-1 and TIMP-3 genes in TSA-treated. In addition, in an in vitro decidualized hESCs model, the increase of TIMP-1 and TIMP-3 expression is associated with histone acetylation at the promoters of these genes. Our results demonstrate that histone acetylation disrupt the balance of ECM modulators provoking a restrain of trophoblast invasion. These findings are important as an epigenetic mechanism that can be used to control trophoblast invasion. PMID:22291969

  13. Parallel approach to incorporating face image information into dialogue processing

    NASA Astrophysics Data System (ADS)

    Ren, Fuji

    2000-10-01

    There are many kinds of so-called irregular expressions in natural dialogues. Even if the content of a conversation is the same in words, different meanings can be interpreted by a person's feeling or face expression. To have a good understanding of dialogues, it is required in a flexible dialogue processing system to infer the speaker's view properly. However, it is difficult to obtain the meaning of the speaker's sentences in various scenes using traditional methods. In this paper, a new approach for dialogue processing that incorporates information from the speaker's face is presented. We first divide conversation statements into several simple tasks. Second, we process each simple task using an independent processor. Third, we employ some speaker's face information to estimate the view of the speakers to solve ambiguities in dialogues. The approach presented in this paper can work efficiently, because independent processors run in parallel, writing partial results to a shared memory, incorporating partial results at appropriate points, and complementing each other. A parallel algorithm and a method for employing the face information in a dialogue machine translation will be discussed, and some results will be included in this paper.

  14. Endometrial carcinoma located in the right septate uterus cavity: a case report

    PubMed Central

    Boubess, Ikram; Mahdi, Youssef; Ramsiss, Hanan; Filali, Adib; Alami, Mohamad Hassan; El khannoussi, Basma; Hachi, Hafid

    2015-01-01

    Endometrial cancer in patients with uterine congenital malformations is exceptional and there are only a few rare cases published in the literature. We report the case of a 67 years-old patient with an endometrial cancer located in the right cavity of a complete septate uterus. PMID:26958135

  15. Use of Outpatient Endometrial Biopsy in a Population with Intellectual Disability

    ERIC Educational Resources Information Center

    Jaffe, Joshua S.

    2008-01-01

    Background: To demonstrate the feasibility of outpatient endometrial sampling to evaluate abnormal uterine bleeding in a population of women with intellectual disability. Method: Retrospective chart review was completed of all endometrial biopsies performed on women attending a dedicated gynaecology clinic for women with intellectual disability…

  16. Expression of Ki-67 as proliferation biomarker in imprint smears of endometrial carcinoma.

    PubMed

    Konstantinos, Kosmas; Marios, Stamoulas; Anna, Marouga; Nikolaos, Kavantzas; Efstratios, Patsouris; Paulina, Athanassiadou

    2013-03-01

    The aims of this study were to determine the expression of Ki-67 in type I and type II endometrial adenocarcinomas as well as normal endometrium in imprint smears and to correlate the results with clinicopathologic parameters of primary untreated endometrial cancer patients. During a 29-month period, 255 patients were evaluated with entometrial imprint cytology. Endometrial samples freshly resected from women who underwent total abdominal hysterectomy were studied. One hundred twenty-six patients had endometrial carcinoma and 129 cases were diagnosed as normal endometrium. The expression of Ki-67 was assessed by immunocytochemistry. Positive staining was correlated with increased stage, grade and lymph node metastases. High expression was more frequent in type II than type I endometrial adenocarcinoma and high-grade endometrial carcinoma had higher proportions of Ki-67 positive immunostaining compared with low-grade carcinoma. Proliferative endometrium showed high Ki-67 expression level, even higher than those of grade 1 and type I. On the other hand, secretory endometrium Ki-67 positive cells were markedly diminished and even disappeared. Completely negative staining was found to be related to atrophic endometrium. Immunocytochemical findings from Ki-67 stain, in addition to cytomorphologic features, appeared to be useful for the diagnosis of endometrial carcinoma in endometrial cytology with imprint smears. High Ki-67 expression correlates with morphologic features of aggressiveness and the expression pattern of Ki-67 correspond to the expected cyclic/atrophic pattern in normal endometrium.

  17. Endometrial tubal metaplasia in a young puerperal woman after breast cancer

    PubMed Central

    Di Benedetto, Luisa; Giovanale, Valentina; Caserta, Donatella

    2015-01-01

    Introduction: Tamoxifen is the usual endocrine (anti-estrogen) therapy for hormone receptor-positive breast cancer in pre and post-menopausal women. Previous studies have suggested an increased prevalence of endometrial diseases after treatment with tamoxifen. Case presentation: The authors report a case of 38-year-old woman with diagnosis of endometrial polyp and tubal metaplasia, during puerperium and after micropapillary ductal breast cancer surgery, 5 years of tamoxifen treatment, spontaneous pregnancy without complications and full-term vaginal delivery. Conclusion: Tamoxifen is a safe and reliable treatment of breast cancer, but data suggest an association with endometrial polyps, hyperplasia, metaplasia and carcinoma. One of the most common types of endometrial metaplasia is ciliated tubal metaplasia. It is generally known that endometrial tubal metaplasia is a benign disease. However studies propose endometrial tubal metaplasia to be a potential premalignant endometrial lesion and its association with endometrial hyperplasia and well-differentiated endometrioid carcinoma. We propose close monitoring of patients taking tamoxifen and prompt evaluation of any uterine bleeding or pelvic complaint or abnormal TVUS images. PMID:26261678

  18. Endometrial carcinoma located in the right septate uterus cavity: a case report.

    PubMed

    Boubess, Ikram; Mahdi, Youssef; Ramsiss, Hanan; Filali, Adib; Alami, Mohamad Hassan; El Khannoussi, Basma; Hachi, Hafid

    2015-01-01

    Endometrial cancer in patients with uterine congenital malformations is exceptional and there are only a few rare cases published in the literature. We report the case of a 67 years-old patient with an endometrial cancer located in the right cavity of a complete septate uterus.

  19. Changes in the Transcriptome of the Human Endometrial Ishikawa Cancer Cell Line Induced by Estrogen, Progesterone, Tamoxifen, and Mifepristone (RU486) as Detected by RNA-Sequencing

    PubMed Central

    Tamm-Rosenstein, Karin; Simm, Jaak; Suhorutshenko, Marina; Salumets, Andres; Metsis, Madis

    2013-01-01

    Background Estrogen (E2) and progesterone (P4) are key players in the maturation of the human endometrium. The corresponding steroid hormone modulators, tamoxifen (TAM) and mifepristone (RU486) are widely used in breast cancer therapy and for contraception purposes, respectively. Methodology/Principal findings Gene expression profiling of the human endometrial Ishikawa cancer cell line treated with E2 and P4 for 3 h and 12 h, and TAM and RU486 for 12 h, was performed using RNA-sequencing. High levels of mRNA were detected for genes, including PSAP, ATP5G2, ATP5H, and GNB2L1 following E2 or P4 treatment. A total of 82 biomarkers for endometrial biology were identified among E2 induced genes, and 93 among P4 responsive genes. Identified biomarkers included: EZH2, MDK, MUC1, SLIT2, and IL6ST, which are genes previously associated with endometrial receptivity. Moreover, 98.8% and 98.6% of E2 and P4 responsive genes in Ishikawa cells, respectively, were also detected in two human mid-secretory endometrial biopsy samples. TAM treatment exhibited both antagonistic and agonistic effects of E2, and also regulated a subset of genes independently. The cell cycle regulator cyclin D1 (CCND1) showed significant up-regulation following treatment with TAM. RU486 did not appear to act as a pure antagonist of P4 and a functional analysis of RU486 response identified genes related to adhesion and apoptosis, including down-regulated genes associated with cell-cell contacts and adhesion as CTNND1, JUP, CDH2, IQGAP1, and COL2A1. Conclusions Significant changes in gene expression by the Ishikawa cell line were detected after treatments with E2, P4, TAM, and RU486. These transcriptome data provide valuable insight into potential biomarkers related to endometrial receptivity, and also facilitate an understanding of the molecular changes that take place in the endometrium in the early stages of breast cancer treatment and contraception usage. PMID:23874806

  20. Prostaglandin release by cultured endometrial tissues after challenge with lipopolysaccharide and tumor necrosis factor α, in relation to the estrous cycle, treatment with medroxyprogesterone acetate, and pyometra.

    PubMed

    Jursza-Piotrowska, Ewelina; Socha, Piotr; Skarzynski, Dariusz Jan; Siemieniuch, Marta Jolanta

    2016-04-01

    To better understand the pathogenesis of endometrial changes in cats associated with administration of progestagen contraceptives and with pyometra, we examined local variability of the prostaglandin synthesis system after challenge with either tumor necrosis factor α (TNF-α) or lipopolysaccharide (LPS) in organ cultures of endometrial tissues derived from cyclic cats, cats treated with medroxyprogesterone acetate (MPA), or cats with pyometra, as well as in cultured endometrial epithelial and stromal cells. In addition, spontaneous prostaglandin secretion was compared in endometria from different experimental groups. Data gathered in the present study show that the concentration of PGE2 in supernatants was increased only in endometrial organ cultures from cats with pyometra (P < 0.001) compared with other groups. This was also true for PGF2α in pyometra, compared with cats treated either short- or long-term with MPA and cats during late diestrus (P < 0.001), anestrus (P < 0.01), and estrus and middiestrus (P < 0.05). Treatment with LPS and TNF-α combined stimulated PGE2 secretion in all groups compared with the control (P < 0.001 for endometria of cats during anestrus or middiestrus, cats treated short-term with MPA, and those with pyometra; P < 0.01 for endometria of cats treated long-term with MPA; and P < 0.05 for the endometria of cats during estrus and late diestrus). The combined treatment with LPS and TNF-α increased PGF2α secretion in the endometria of cats treated short-term with MPA (P < 0.001), during anestrus and pyometra (P < 0.01 for both), and estrus and middiestrus (P < 0.05 for both), compared with the control. Spontaneous secretion of prostaglandins was several times greater in the endometria of queens with pyometra, compared with other groups, which may further regulate the local inflammatory response. Data gathered from endometrial cell culture and endometrial organ culture lead to the conclusion that disturbances in prostaglandin release

  1. Paclitaxel, Carboplatin, and Bevacizumab or Paclitaxel, Carboplatin, and Temsirolimus or Ixabepilone, Carboplatin, and Bevacizumab in Treating Patients With Stage III, Stage IV, or Recurrent Endometrial Cancer

    ClinicalTrials.gov

    2017-01-31

    Endometrial Adenocarcinoma; Endometrial Adenosquamous Carcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Serous 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

  2. A study of the influence of a gestodene-containing triphasic oral contraceptive on endometrial morphology.

    PubMed

    Rabe, T; Leppien, G; Fossman, W G; Hessing, C; Vladescú, E; Runnebaum, B

    1997-09-01

    The objective of the study was to investigate histological changes in the endometrium in 20 volunteers treated with a low-dose, gestodene-containing triphasic oral contraceptive. Endometrial biopsy specimens were taken before, during a 6-month period of oral contraceptive use and in a post-treatment period. These specimens were evaluated using light microscopy, scanning and transmission electron microscopy. In addition, ultrasound examinations of the uterus, endometrial thickness and ovaries were performed. The low-dose, gestodene-containing triphasic oral contraceptive had no adverse effects on the endometrium (e.g. no proliferation, no polyps, no inflammatory processes), was well tolerated and showed a low side-effect profile. The inhibition of endometrial transformation was demonstrated both by endometrial morphology as well as by endometrial thickness, as measured by transvaginal ultrasound examination.

  3. Comparison of Pipelle sampler with conventional dilatation and curettage (D&C) for Chinese endometrial biopsy.

    PubMed

    Liu, H; Wang, F-L; Zhao, Y-M; Yao, Y-Q; Li, Y-L

    2015-01-01

    The aim of this study is to investigate the accuracy and adequacy of the Pipelle endometrial sampler for endometrial biopsy as compared with those of conventional dilatation and curettage (D&C). A total of 245 patients subject to endometrial biopsy were included in this study. We have shown that the failure rates with D&C and Pipelle were 7.75% and 8.98%, respectively, without statistical difference. Additionally, the obtained specimen quality and accurate diagnosis of various diseases using the two methods had no significant statistical differences. Furthermore, patients experienced less pain when Pipelle sampler was used than D&C. Therefore, Pipelle sampler is effective in obtaining adequate endometrial tissue for histodiagnosis, and is applicable in most of the cases for Chinese endometrial biopsy.

  4. Immunohistochemical analysis of ras oncogene product p21 in human endometrial carcinoma.

    PubMed

    Yaginuma, Y; Fujita, M; Saitoh, S; Hayakawa, K; Kuzumaki, N; Ishikawa, M

    1993-09-01

    Monoclonal antibody rp-28 directed against the ras gene product p21 has been used to evaluate ras p21 expression in endometrial lesions. Endometrial cancer showed a variable reactivity according to histological type: in well differentiated adenocarcinoma 63% were positive (12/19); in moderately differentiated adenocarcinoma 53% were positive (8/15); in poorly differentiated adenocarcinoma 40% were positive (2/5). The staining intensity of ras p21 seemed to be stronger in the more differentiated types of endometrial carcinoma. In endometrial carcinoma with premenopausal women, 27% were positive (3/11), and with postmenopausal women 71% were positive (20/28). The difference between premenopausal and postmenopausal groups was statistically significant (Mantel-Haenszel procedure, M-H chi 2 = 6.765, P < 0.01). The results suggest the existence of different carcinogenetic mechanisms in these two groups of endometrial cancer.

  5. P53 and Murine Double Mimute 2 (MDM2) Expression Changes and Significance in Different Types of Endometrial Lesions

    PubMed Central

    Jiang, Zhongyong; Xu, Wanqing; Dan, Gang; Liu, Yuan; Xiong, Jie

    2016-01-01

    Background Endometrial lesions are common in obstetrics and gynecology, including endometrial polyps, uterine adenomyosis, and malignant endometrial adenocarcinoma. Endometrial lesions seriously affect women’s health, fertility, quality of life, and life safety. As a pro-apoptosis gene, p53 is considered to be closely related with human tumors. Murine double mimute 2 (MDM2) is an oncogene that can promote tumor occurrence and development. P53 and MDM2 expression and significance in different types of endometrial lesions have not been fully elucidated. Material/Methods Normal endometrium, endometrial polyps, uterine adenomyosis, and endometrial adenocarcinoma tissue samples were collected. Real-time PCR was used to detect p53 and MDM2 mRNA expression. Immunohistochemical staining and Western blot analysis were applied to test p53 and MDM2 protein expression. Their correlation with clinical staging of endometrial adenocarcinoma was analyzed. Results P53 and MDM2 mRNA and protein expression were significantly elevated in the endometrial polyps group and the endometrial adenocarcinoma group compared with the normal control group (P<0.05). Their levels increased more obviously in endometrial adenocarcinoma compared with endometrial polyps (P<0.05). P53 and MDM2 mRNA and protein expression were slightly enhanced in uterine adenomyosis compared with normal controls, but this difference lacked statistical significance (P>0.05). P53 and MDM2 mRNA and protein level showed a positive correlation. Significantly higher expression of p53 or MDM2 was observed in patients with stage III compared to those in patients with stage II. Higher expression was also observed in patients with stage II than in patients with stage I. Conclusions P53 and MDM2 mRNA and protein were elevated in endometrial polyps and endometrial adenocarcinoma and their expressions were correlated with clinical staging of endometrial adenocarcinoma. They can promote cancer occurrence and development, and can

  6. [New endometrial modulators in early pregnancy].

    PubMed

    Díaz-Flores, M; Baiza-Gutman, L A; Hicks, J J

    1996-01-01

    Cytokines synthesized by the uterus or placenta include those thought to be produced exclusively by, or though to act on, cells of the lymphohematopoietic system. Although many of these cytokines are protein mediators of the immune system effector phase, in the female reproductive tract their principal target cells and sites of synthesis are non-lymphohematopoietic cells. During pregnancy, uterine epithelial cells, decidual cells and trophoblast appear to be major sources of the classic lymphohematopoietic cytokines. This suggests two not necessarily exclusive alternatives: that these cells are extensions of, or are involved in, regulating the immune system, or that these factors regulate growth and differentiation of uterine and embryonic tissues. This paper analyzes the sites of synthesis, targets and possible functions of the cytokines during early pregnancy.

  7. Ragnar Rommetveit's Approach to Everyday Spoken Dialogue from Within.

    PubMed

    Kowal, Sabine; O'Connell, Daniel C

    2016-04-01

    The following article presents basic concepts and methods of Ragnar Rommetveit's (born 1924) hermeneutic-dialogical approach to everyday spoken dialogue with a focus on both shared consciousness and linguistically mediated meaning. He developed this approach originally in his engagement of mainstream linguistic and psycholinguistic research of the 1960s and 1970s. He criticized this research tradition for its individualistic orientation and its adherence to experimental methodology which did not allow the engagement of interactively established meaning and understanding in everyday spoken dialogue. As a social psychologist influenced by phenomenological philosophy, Rommetveit opted for an alternative conceptualization of such dialogue as a contextualized, partially private world, temporarily co-established by interlocutors on the basis of shared consciousness. He argued that everyday spoken dialogue should be investigated from within, i.e., from the perspectives of the interlocutors and from a psychology of the second person. Hence, he developed his approach with an emphasis on intersubjectivity, perspectivity and perspectival relativity, meaning potential of utterances, and epistemic responsibility of interlocutors. In his methods, he limited himself for the most part to casuistic analyses, i.e., logical analyses of fictitious examples to argue for the plausibility of his approach. After many years of experimental research on language, he pursued his phenomenologically oriented research on dialogue in English-language publications from the late 1980s up to 2003. During that period, he engaged psycholinguistic research on spoken dialogue carried out by Anglo-American colleagues only occasionally. Although his work remained unfinished and open to development, it provides both a challenging alternative and supplement to current Anglo-American research on spoken dialogue and some overlap therewith.

  8. Methylation Analysis of DNA Mismatch Repair Genes Using DNA Derived from the Peripheral Blood of Patients with Endometrial Cancer: Epimutation in Endometrial Carcinogenesis

    PubMed Central

    Takeda, Takashi; Banno, Kouji; Yanokura, Megumi; Adachi, Masataka; Iijima, Moito; Kunitomi, Haruko; Nakamura, Kanako; Iida, Miho; Nogami, Yuya; Umene, Kiyoko; Masuda, Kenta; Kobayashi, Yusuke; Yamagami, Wataru; Hirasawa, Akira; Tominaga, Eiichiro; Susumu, Nobuyuki; Aoki, Daisuke

    2016-01-01

    Germline mutation of DNA mismatch repair (MMR) genes is a cause of Lynch syndrome. Methylation of MutL homolog 1 (MLH1) and MutS homolog 2 (MSH2) has been detected in peripheral blood cells of patients with colorectal cancer. This methylation is referred to as epimutation. Methylation of these genes has not been studied in an unselected series of endometrial cancer cases. Therefore, we examined methylation of MLH1, MSH2, and MSH6 promoter regions of peripheral blood cells in 206 patients with endometrial cancer using a methylation-specific polymerase chain reaction (MSP). Germline mutation of MMR genes, microsatellite instability (MSI), and immunohistochemistry (IHC) were also analyzed in each case with epimutation. MLH1 epimutation was detected in a single patient out of a total of 206 (0.49%)—1 out of 58 (1.72%) with an onset age of less than 50 years. The patient with MLH1 epimutation showed high level MSI (MSI-H), loss of MLH1 expression and had developed endometrial cancer at 46 years old, complicated with colorectal cancer. No case had epimutation of MSH2 or MSH6. The MLH1 epimutation detected in a patient with endometrial cancer may be a cause of endometrial carcinogenesis. This result indicates that it is important to check epimutation in patients with endometrial cancer without a germline mutation of MMR genes. PMID:27754426

  9. Endometrial receptivity: expression of alpha3beta1, alpha4beta1 and alphaVbeta1 endometrial integrins in women with impaired fertility.

    PubMed

    Skrzypczak, J; Mikołajczyk, M; Szymanowski, K

    2001-11-01

    Advances in immunohistochemical methods with the specificity of poly- and monoclonal antibodies allow the description of the endometrial receptivity, which is characterized by the ability of secretion of phase specific proteins and glikoproteins by epithelial and stromal cells. We studied the differences in the expression of alpha3beta1, alpha4beta1 and alphaVbeta1 integrins in endometrium of women with recurrent miscarriages and women with unexplained infertility. The endometrial tissue was collected during hysteroscopy performed between 7th and 9th day after ovulation. The immunohistochemical evaluation of alpha3beta1, alpha4beta1 and alphaVbeta1 integrin expression was determined in all endometrial biopsies. Staining intensity of alpha3beta1 in glandular epithelium and endometrial stroma was similar in both groups. In women with recurrent miscarriages we noted a lower concentrations of the alpha4beta1 and alphaVbeta1 integrins during the midluteal phase than in women with unexplained infertility. Moreover, integrins alpha4beta1 and alphaVbeta1 were expressed more frequently in glandular epithelium and endometrial stroma of women with unexplained infertility than those of women with recurrent miscarriages. However, alphaV(2)1 staining in endometrial stroma was stronger than that of alpha4beta1. It can be concluded, that these integrins may play an important role in the implantation process.

  10. Urokinase-type Plasminogen Activator Resulting from Endometrial Carcinogenesis Enhances Tumor Invasion and Correlates with Poor Outcome of Endometrial Carcinoma Patients

    PubMed Central

    Huang, Chia-Yen; Chang, Ming-Cheng; Huang, Wei-Yun; Huang, Ching-Ting; Tang, Yu-Chien; Huang, Hsien-Da; Kuo, Kuan-Ting; Chen, Chi-An; Cheng, Wen-Fang

    2015-01-01

    The purpose of this study was to identify the dysregulated genes involved in the tumorigenesis and progression of endometrial endometrioid adenocarcinoma (EEC), and their possible mechanisms. Endometrial specimens including normal endometrial tissues, atypical endometrial hyperplasia, and EEC were analyzed. The expression profiles were compared using GeneChip Array. The gene expression levels were determined by real-time RT-PCR in the training and testing sets to correlate the clinico-pathological parameters of EEC. Immunoblotting, in vitro cell migration and invasion assays were performed in human endometrial cancer cell lines and their transfectants. In microarray analysis, seven dysregulated genes were identified. Only the levels of urokinase-type plasminogen activator (uPA) were higher in EEC with deep myometrial invasion, positive lympho-vascular space invasion, lymph node metastasis, and advanced stages. After multivariate analysis, uPA was the only independent poor prognostic factor for disease-free survival in the EEC patients (hazard ratio: 4.65, p = 0.03). uPA may enhance the migratory and invasive capabilities of endometrial tumor cells by the phosphorylation of ERK1/2, Akt and p38 molecules. uPA is a dysregulated gene involved in the tumorigenesis, bio-pathological features and outcomes of EEC. uPA may be a potential molecule and target for the detection and treatment of EEC. PMID:26033187

  11. Methylation Analysis of DNA Mismatch Repair Genes Using DNA Derived from the Peripheral Blood of Patients with Endometrial Cancer: Epimutation in Endometrial Carcinogenesis.

    PubMed

    Takeda, Takashi; Banno, Kouji; Yanokura, Megumi; Adachi, Masataka; Iijima, Moito; Kunitomi, Haruko; Nakamura, Kanako; Iida, Miho; Nogami, Yuya; Umene, Kiyoko; Masuda, Kenta; Kobayashi, Yusuke; Yamagami, Wataru; Hirasawa, Akira; Tominaga, Eiichiro; Susumu, Nobuyuki; Aoki, Daisuke

    2016-10-14

    Germline mutation of DNA mismatch repair (MMR) genes is a cause of Lynch syndrome. Methylation of MutL homolog 1 (MLH1) and MutS homolog 2 (MSH2) has been detected in peripheral blood cells of patients with colorectal cancer. This methylation is referred to as epimutation. Methylation of these genes has not been studied in an unselected series of endometrial cancer cases. Therefore, we examined methylation of MLH1, MSH2, and MSH6 promoter regions of peripheral blood cells in 206 patients with endometrial cancer using a methylation-specific polymerase chain reaction (MSP). Germline mutation of MMR genes, microsatellite instability (MSI), and immunohistochemistry (IHC) were also analyzed in each case with epimutation. MLH1 epimutation was detected in a single patient out of a total of 206 (0.49%)-1 out of 58 (1.72%) with an onset age of less than 50 years. The patient with MLH1 epimutation showed high level MSI (MSI-H), loss of MLH1 expression and had developed endometrial cancer at 46 years old, complicated with colorectal cancer. No case had epimutation of MSH2 or MSH6. The MLH1 epimutation detected in a patient with endometrial cancer may be a cause of endometrial carcinogenesis. This result indicates that it is important to check epimutation in patients with endometrial cancer without a germline mutation of MMR genes.

  12. Peritoneal Fluid Reduces Angiogenesis-Related MicroRNA Expression in Cell Cultures of Endometrial and Endometriotic Tissues from Women with Endometriosis

    PubMed Central

    Braza-Boïls, Aitana; Gilabert-Estellés, Juan; Ramón, Luis A.; Gilabert, Juan; Marí-Alexandre, Josep; Chirivella, Melitina; España, Francisco; Estellés, Amparo

    2013-01-01

    Endometriosis, defined as the presence of endometrium outside the uterus, is one of the most frequent gynecological diseases. It has been suggested that modifications of both endometrial and peritoneal factors could be implicated in this disease. Endometriosis is a multifactorial disease in which angiogenesis and proteolysis are dysregulated. MicroRNAs (miRNAs) are small non-coding RNAs that regulate the protein expression and may be the main regulators of angiogenesis. Our hypothesis is that peritoneal fluid from women with endometriosis could modify the expression of several miRNAs that regulate angiogenesis and proteolysis in the endometriosis development. The objective of this study has been to evaluate the influence of endometriotic peritoneal fluid on the expression of six miRNAs related to angiogenesis, as well as several angiogenic and proteolytic factors in endometrial and endometriotic cell cultures from women with endometriosis compared with women without endometriosis. Methods Endometrial and endometriotic cells were cultured and treated with endometriotic and control peritoneal fluid pools. We have studied the expression of six miRNAs (miR-16, -17-5p, -20a, -125a, -221, and -222) by RT-PCR and protein and mRNA levels of vascular endothelial growth factor-A, thrombospondin-1, urokinase plasminogen activator and plasminogen activator inhibitor-1 by ELISA and qRT-PCR respectively. Results Control and endometriotic peritoneal fluid pools induced a significant reduction of all miRNAs levels in endometrial and endometriotic cell cultures. Moreover, both peritoneal fluids induced a significant increase in VEGF-A, uPA and PAI-1 protein levels in all cell cultures without significant increase in mRNA levels. Endometrial cell cultures from patients treated with endometriotic peritoneal fluid showed lower expression of miRNAs and higher expression of VEGF-A protein levels than cultures from controls. In conclusion, this “in vitro” study indicates that

  13. Cancer-Related Triplets of mRNA-lncRNA-miRNA Revealed by Integrative Network in Uterine Corpus Endometrial Carcinoma

    PubMed Central

    Zhang, Yu-Hang; Deng, Qinfang

    2017-01-01

    The regulation of transcriptome expression level is a complex process involving multiple-level interactions among molecules such as protein coding RNA (mRNA), long noncoding RNA (lncRNA), and microRNA (miRNA), which are essential for the transcriptome stability and maintenance and regulation of body homeostasis. The availability of multilevel expression data enables a comprehensive view of the regulatory network. In this study, we analyzed the coding and noncoding gene expression profiles of 301 patients with uterine corpus endometrial carcinoma (UCEC). A new method was proposed to construct a genome-wide integrative network based on variance inflation factor (VIF) regression method. The cross-regulation relations of mRNA, lncRNA, and miRNA were then selected based on clique-searching algorithm from the network, when any two molecules of the three were shown as interacting according to the integrative network. Such relation, which we call the mRNA-lncRNA-miRNA triplet, demonstrated the complexity in transcriptome regulation process. Finally, six UCEC-related triplets were selected in which the mRNA participates in endometrial carcinoma pathway, such as CDH1 and TP53. The multi-type RNAs are proved to be cross-regulated as to each of the six triplets according to literature. All the triplets demonstrated the association with the initiation and progression of UCEC. Our method provides a comprehensive strategy for the investigation of transcriptome regulation mechanism. PMID:28280730

  14. The Chinese herbs Scutellaria baicalensis and Fritillaria cirrhosa target NFκB to inhibit proliferation of ovarian and endometrial cancer cells.

    PubMed

    Kavandi, Leyla; Lee, Laura R; Bokhari, Amber A; Pirog, John E; Jiang, Yongping; Ahmad, Kashif A; Syed, Viqar

    2015-05-01

    The herbs Scutellaria baicalensis (SB) and Fritillaria cirrhosa (FC) are widely used in Chinese medicine to treat several aliments and as an adjuvant to chemotherapy of lung cancer. No information is available regarding the two herbs' influence on ovarian and endometrial cancer. To fill this data gap we compared cell growth responses to SB and FC in ovarian and endometrial cancer cell lines. Dose-dependent cell growth inhibition was observed following higher doses in all cell lines while lower doses stimulated growth in only endometrial cell lines. Higher doses of SB and FC significantly decreased cell growth on soft agar and decreased the invasive potential of cancer cells. Treatment of cells with both herbs resulted in activation of caspase-3, G0 /G1 phase cell cycle arrest, downregulation of cyclins D1 and D3 and induction of p27. Both herbs decreased NFκB DNA binding, reduced expression of phosphorylated IκBα, abrogated NFκB activation, and downregulated NFκB-regulated metastasis-promoting proteins in cancer cells. Furthermore, knockdown of NFκB attenuated SB- and FC-induced cell growth inhibition. These results suggest that inhibition of NFκB activation may be an important mechanism for growth suppression by SB and FC. Data indicate that these herbs may represent a new source of agents for NFκB inhibition in cancer therapy.

  15. Methylation profiles of endometrioid and serous endometrial cancers.

    PubMed

    Seeber, Laura M S; Zweemer, Ronald P; Marchionni, Luigi; Massuger, Leon F A G; Smit, Vincent T H B M; van Baal, W Marchien; Verheijen, René H M; van Diest, Paul J

    2010-09-01

    Promoter methylation is a gene- and cancer type-specific epigenetic event that plays an important role in tumour development. As endometrioid (endometrioid endometrial carcinoma, EEC) and serous endometrial cancers (uterine papillary serous carcinoma, UPSC) exhibit different clinical, histological and molecular genetic characteristics, we hypothesized that these differences may be reflected in epigenetic phenomena as well. Identification of a panel of methylation biomarkers could be helpful in a correct histological classification of these two subtypes, which solely on the basis of morphology is not always easy. Methylation-specific multiplex ligation-dependent probe amplification was used to assess the extent of promoter methylation of different tumour suppressor genes in EEC and UPSC. Methylation results were correlated with histology and survival. The median cumulative methylation index of all genes was significantly higher in EEC (124) than in UPSC (93) (P<0.001). Promoter methylation of CDH13 and MLH1 was more frequently present in EEC, while CDKN2B and TP73 were more frequently methylated in UPSC. Almost 90% of EEC and 70% of UPSC could be predicted by CDH13 and TP73. In EEC, methylation of MLH1 was associated with a shorter disease-free survival (DFS; P<0.0001) and overall survival (OS; P=0.005). In a multivariate model, MLH1 methylation emerged as an additional prognostic factor to stage for DFS (P=0.002). In conclusion, promoter methylation is more common in EEC than UPSC. A panel of methylation biomarkers could be useful to distinguish between the two histological subtypes of endometrial cancer. Furthermore, methylation of MLH1 may have prognostic value in EEC.

  16. Odds ratio analysis in women with endometrial cancer

    PubMed Central

    Żak, Ewa; Pięta, Beata

    2016-01-01

    Introduction Despite the progress in diagnosis and treatment of malignant tumours, the effects of treatment are insufficient. Reduction of the risk of cervical, ovarian, and endometrial cancer is possible by introducing preventative actions. Aim of the study The aim of the thesis is the analysis of selected risk factors that may affect the increase or decrease in the odds ratio of developing endometrial cancer. Material and methods The study was conducted among patients of the Gynaecology and Obstetrics Hospital of Poznań University of Medical Sciences in the years 2011-2013. The research included a total of 548 female respondents aged between 40 and 84 years. Women responded to questions assessing elements of lifestyle such as consumption of alcohol, smoking, and eating certain groups of foods. Results The respondents consuming fruits and vegetables several times a week have a reduced risk of odds ratio and the OR is 0.85; 95% CI: 0.18-4.09, compared to the women who rarely consume vegetables and fruits. Consumption of whole-wheat bread several times a week reduces the risk of developing the cancer, OR = 0.59; 95% CI: 0.14-2.47, compared to women not consuming wholegrain bread at all. Respondents who consumed red meat, such as veal, pork, and lamb in the amount of 101-200 g per day have an increased risk of developing the disease: OR = 2.16; 95% CI: 1.09-4.28, compared to women not consuming red meat at all. Conclusions A diet rich in fruit and vegetables, onions, garlic, whole grains, and beans should be introduced in order to reduce the risk of endometrial cancer. The consumption of red meat and white pasta should be reduced or even eliminated. PMID:27095953

  17. Photoaffinity labeling of the progesterone receptor from human endometrial carcinoma

    SciTech Connect

    Clarke, C.L.; Satyaswaroop, P.G.

    1985-11-01

    A nude mouse model for the growth of human endometrial carcinoma and hormonal modulation of the progesterone receptor (PR) was established previously. This study describes the effect of 17 beta-estradiol and tamoxifen (TAM) on growth rate and PR concentration in a hormonally responsive human endometrial tumor (EnCa 101) grown in this experimental system and presents the first characterization of human endometrial carcinoma PR. EnCa 101 was transplanted subcutaneously into ovariectomized, BALB/c, nu/nu athymic mice and grown under 17 beta-estradiol-stimulated, TAM-stimulated, and control conditions. Both 17 beta-estradiol and TAM increased the growth rate of EnCa 101 in nude mice, and a parallel increase in the cytosol PR concentration was observed. PR was partially purified by phosphocellulose and DEAE cellulose chromatography, and the DEAE eluate was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and photoaffinity labeling with (17 alpha-methyl-TH)promegestone ((TH)R5020). Two PR-negative tumors (EnCa K and EnCa V) were also examined in parallel. Photolabeling and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of EnCa 101 grown in the presence of 17 beta-estradiol or TAM revealed incorporation of (3H)R5020 into proteins of molecular weight approximately 116,000 and 85,000. Labeled proteins of molecular weight 66,000, 45,000, and 35,000 were also observed. No incorporation of (TH)R5020 was observed in EnCa 101 grown in the absence of estrogen, nor was any observed in EnCa K or EnCa V.

  18. Distribution of estrogen and progesterone receptors isoforms in endometrial cancer

    PubMed Central

    2014-01-01

    Background 70–80% of sporadic endometrial carcinomas are defined as endometrioid carcinoma (EC). Early-stage, well differentiated endometrial carcinomas usually retain expression of estrogen and progesterone receptors (ER and PR, respectively), as advanced stage, poorly differentiated tumors often lack one or both of these receptors. Well-described EC prognosis includes tumor characteristics, such as depth of myometrial invasion. Therefore, in the current study, we evaluated the expression profile of ER and PR isoforms, including ER-α, PR-A and PR–B, in correlation to EC tumor histological depth. Methods Using immunohistochemistry and image analysis software, the expression of ER-α, PR-A, PR–B and Ki67 was assessed in endometrial stroma and epithelial glands of superficial, deep and extra-tumoral sections of 15 paraffin embedded EC specimens, and compared to 5 biopsies of non-malignant endometrium. Results Expression of PR-A and ER-α was found to be lower in EC compared to nonmalignant tissue, as the stromal expression was dramatically reduced compared to epithelial cells. Expression ratios of both receptors were significantly high in superficial and deep portions of EC; in non-tumoral portion of EC were close to the ratios of nonmalignant endometrium. PR-B expression was low in epithelial glands of EC superficial and deep portions, and high in the extra-tumoral region. Elevated PR-B expression was found in stroma of EC, as well. Conclusions The ratio of ER-α and PR-A expression in the epithelial glands and the stroma of EC biopsies may serve as an additional parameter in the histological evaluation of EC tumor. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1155060506119016 PMID:24684970

  19. Second-generation endometrial ablation technologies: the hot liquid balloons.

    PubMed

    Vilos, George A; Edris, Fawaz

    2007-12-01

    Hysteroscopic endometrial ablation (HEA) was introduced in the 1980s to treat menorrhagia. Its use required additional training, surgical expertise and specialized equipment to minimize emergent complications such as uterine perforations, thermal injuries and excessive fluid absorption. To overcome these difficulties and concerns, thermal balloon endometrial ablation (TBEA) was introduced in the 1990s. Four hot liquid balloons have been introduced into clinical practice. All systems consist of a catheter (4-10mm diameter), a silicone balloon and a control unit. Liquids used to inflate the balloons include internally heated dextrose in water (ThermaChoice, 87 degrees C), and externally heated glycine (Cavaterm, 78 degrees C), saline (Menotreat, 85 degrees ) and glycerine (Thermablate, 173 degrees C). All balloons require pressurization from 160 to 240 mmHg for treatment cycles of 2 to 10 minutes. Prior to TBEA, preoperative endometrial thinning, including suction curettage, is optional. Several RCTs and cohort studies indicate that the advantages of TBEA include portability, ease of use and short learning curve. In addition, small diameter catheters requiring minimal cervical dilatation (5-7 mm) and short duration of treatment cycles (2-8 min) allow treatment under minimal analgesia/anesthesia requirements in a clinic setting. Following TBEA serious adverse events, including thermal injuries to viscera have been experienced. To minimize such injuries some surgeons advocate the use of routine post-dilatation hysteroscopy and/or ultrasonography to confirm correct intrauterine placement of the balloon prior to initiating the treatment cycle. After 10 years of clinical practice, TBEA is thought to be the preferred first-line surgical treatment of menorrhagia in appropriately selected candidates. Economic modeling also suggested that TBEA may be more cost-effective than HEA.

  20. TP53 Mutational Spectrum in Endometrioid and Serous Endometrial Cancers.

    PubMed

    Schultheis, Anne M; Martelotto, Luciano G; De Filippo, Maria R; Piscuglio, Salvatore; Ng, Charlotte K Y; Hussein, Yaser R; Reis-Filho, Jorge S; Soslow, Robert A; Weigelt, Britta

    2016-07-01

    Endometrial carcinomas (ECs) are heterogeneous at the genetic level. Although TP53 mutations are highly recurrent in serous endometrial carcinomas (SECs), these are also present in a subset of endometrioid endometrial carcinomas (EECs). Here, we sought to define the frequency, pattern, distribution, and type of TP53 somatic mutations in ECs by performing a reanalysis of the publicly available data from The Cancer Genome Atlas (TCGA). A total of 228 EECs (n=186) and SECs (n=42) from the TCGA data set, for which an integrated genomic characterization was performed, were interrogated for the presence and type of TP53 mutations, and for mutations in genes frequently mutated in ECs. TP53 mutations were found in 15% of EECs and 88% of SECs, and in 91% of copy-number-high and 35% of polymerase (DNA directed), epsilon, catalytic subunit (POLE) integrative genomic subtypes. In addition to differences in prevalence, variations in the type and pattern of TP53 mutations were observed between histologic types and between integrative genomic subtypes. TP53 hotspot mutations were significantly more frequently found in SECs (46%) than in EECs (15%). TP53-mutant EECs significantly more frequently harbored a co-occurring PTEN mutation than TP53-mutant SECs. Finally, a subset of TP53-mutant ECs (22%) was found to harbor frameshift or nonsense mutations. Given that nonsense and frameshift TP53 mutations result in distinct p53 immunohistochemical results that require careful interpretation, and that EECs and SECs display different patterns, types, and distributions of TP53 mutations, the use of the TP53/p53 status alone for the differential diagnosis of EECs and SECs may not be sufficient.

  1. Pro-protein convertases (PCs) other than PC6 are not tightly regulated for implantation in the human endometrium.

    PubMed

    Freyer, C; Kilpatrick, L M; Salamonsen, L A; Nie, G

    2007-06-01

    Pro-protein convertases (PCs) are a family of serine proteases (furin, PC1/3, PC2, PACE4, PC4, PC5/6, PC7/8) responsible for post-translational processing and activation of inactive precursors of many regulatory proteins. Endometrial PC6 is critical for implantation in mice and for decidualization of human endometrial stromal cells (ESCs). This study investigated the endometrial expression of other PCs during the menstrual cycle and early pregnancy to elucidate potential redundancies. Furin, PC4, PACE4, and PC7 along with PC6 transcripts were detected in total endometrial RNA, whereas PC1 and PC2 transcription levels were negligible. Quantitative RT-PCR demonstrated highest levels of furin mRNA during menstruation and lowest levels during the proliferative phase. Furin protein was immunolocalized in endometrial luminal and glandular epithelia, stromal fibroblasts, endothelia, and leukocytes. PACE4 and PC7 proteins were also immunodetected in endometrial stroma and glands. Total furin, PC7, and PACE4 proteins were constitutive in both stromal and glandular compartments throughout the cycle and during first trimester pregnancy. Furthermore, Furin and PC7 transcription was unaltered during decidualization of ESCs in vitro in contrast to PC6 which is significantly up-regulated during decidualization. Thus, whereas PC6 is tightly regulated during endometrial preparation for implantation, furin, PACE4, and PC7 are constitutively expressed in human endometrium, but must be considered if PC6 is to be targeted for manipulation of fertility.

  2. Treatment of Endometrial Cancer in Association with Pelvic Organ Prolapse

    PubMed Central

    Vanichtantikul, Asama; Tharavichitkul, Ekkasit; Chitapanarux, Imjai

    2017-01-01

    Background. Uterine malignancy coexistent with pelvic organ prolapse (POP) is uncommon and standardized treatment is not established. The objective of this case study was to highlight the management of endometrial cancer in association with pelvic organ prolapse. Case Report. An 87-year-old woman presented with POP Stage IV combined with endometrioid adenocarcinoma of the uterus: clinical Stage IV B. She had multiple medical conditions including stroke, deep vein thrombosis, and pulmonary embolism. She was treated with radiotherapy and pessary was placed. Conclusion. Genital prolapse with abnormal uterine bleeding requires proper evaluation and management. Concurrent adenocarcinoma and POP can be a difficult clinical situation to treat, and optimum management is controversial.

  3. Diagnostic value of circulating miR-21: An update meta-analysis in various cancers and validation in endometrial cancer.

    PubMed

    Gao, Yun; Dai, Meiyu; Liu, Haihua; He, Wangjiao; Lin, Shengzhang; Yuan, Tianzhu; Chen, Hong; Dai, Shengming

    2016-10-18

    MiR-21 has been identified as one of the most common proto-oncogenes. It is hypothesized that up-regulated miR-21 could be served as a potential biomarker for human cancer diagnosis. However, inconsistencies or discrepancies about diagnostic accuracy of circulating miR-21 still remain. In this sense, miR-21's diagnostic value needs to be fully validated. In this study, we performed an update meta-analysis to estimate the diagnostic value of circulating miR-21 in various human cancers. Additionally, we conducted a validation test on 50 endometrial cancer patients, 50 benign lesion patients and 50 healthy controls. A systematical literature search for relevant articles was performed in Pubmed, Embase and Cochrane Library. A total of 48 studies from 39 articles, involving 3,568 cancer patients and 2,248 controls, were included in this meta-analysis. The overall sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and area under the curve (AUC) were 0.76 (0.71-0.80), 0.82 (0.79-0.85), 4.3 (3.6-5.1), 0.29 (0.24-0.35), 15 (11-20) and 0.86 (0.83-0.89), respectively. In the validation test, the expression levels of serum miR-21 were significantly higher in benign lesion patients (p = 0.003) and endometrial cancer patients (p = 0.000) compared with that of healthy controls. Endometrial cancer patients showed higher miR-21 expression levels (p = 0.000) compared with benign lesion patients. In conclusion, the meta-analysis shows that circulating miR-21 has excellent performance on the diagnosis for various cancers and the validation test demonstrates that serum miR-21 could be served as a novel biomarker for endometrial carcinoma.

  4. Diagnostic value of circulating miR-21: An update meta-analysis in various cancers and validation in endometrial cancer

    PubMed Central

    Liu, Haihua; He, Wangjiao; Lin, Shengzhang; Yuan, Tianzhu; Chen, Hong; Dai, Shengming

    2016-01-01

    MiR-21 has been identified as one of the most common proto-oncogenes. It is hypothesized that up-regulated miR-21 could be served as a potential biomarker for human cancer diagnosis. However, inconsistencies or discrepancies about diagnostic accuracy of circulating miR-21 still remain. In this sense, miR-21′s diagnostic value needs to be fully validated. In this study, we performed an update meta-analysis to estimate the diagnostic value of circulating miR-21 in various human cancers. Additionally, we conducted a validation test on 50 endometrial cancer patients, 50 benign lesion patients and 50 healthy controls. A systematical literature search for relevant articles was performed in Pubmed, Embase and Cochrane Library. A total of 48 studies from 39 articles, involving 3,568 cancer patients and 2,248 controls, were included in this meta-analysis. The overall sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and area under the curve (AUC) were 0.76 (0.71-0.80), 0.82 (0.79-0.85), 4.3 (3.6-5.1), 0.29 (0.24-0.35), 15 (11-20) and 0.86 (0.83-0.89), respectively. In the validation test, the expression levels of serum miR-21 were significantly higher in benign lesion patients (p = 0.003) and endometrial cancer patients (p = 0.000) compared with that of healthy controls. Endometrial cancer patients showed higher miR-21 expression levels (p = 0.000) compared with benign lesion patients. In conclusion, the meta-analysis shows that circulating miR-21 has excellent performance on the diagnosis for various cancers and the validation test demonstrates that serum miR-21 could be served as a novel biomarker for endometrial carcinoma. PMID:27655698

  5. Fludeoxyglucose F 18 PET Scan, CT Scan, and Ferumoxtran-10 MRI Scan Before Chemotherapy and Radiation Therapy in Finding Lymph Node Metastasis in Patients With Locally Advanced Cervical Cancer or High-Risk Endometrial Cancer

    ClinicalTrials.gov

    2016-11-14

    Cervical Adenocarcinoma; Cervical Adenosquamous Cell Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma; Endometrial Clear Cell Carcinoma; Endometrial Papillary Serous Carcinoma; Stage I Endometrial Carcinoma; Stage IB Cervical Cancer; Stage II Endometrial Carcinoma; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage III Endometrial Carcinoma; Stage IVA Cervical Cancer

  6. Evidence for estrogen-dependent uterine serpin (SERPINA14) expression during estrus in the bovine endometrial glandular epithelium and lumen.

    PubMed

    Ulbrich, Susanne E; Frohlich, Thomas; Schulke, Katy; Englberger, Eva; Waldschmitt, Nadine; Arnold, Georg J; Reichenbach, Horst-Dieter; Reichenbach, Myriam; Wolf, Eckhard; Meyer, Heinrich H D; Bauersachs, Stefan

    2009-10-01

    Uterine secretions have a dominant impact on the environment in which embryo development takes place. The uterine serpins (SERPINA14, previously known as UTMP) are found most abundantly during pregnancy in the uterus of ruminants. Although progesterone is currently assumed to be the major regulator of SERPINA14 expression, our recent study of transcriptome changes in bovine endometrium during the estrous cycle unexpectedly detected a marked upregulation of SERPINA14 mRNA levels at estrus. The present study describes the full-length mRNA sequence, genomic organization, and putative promoter elements of the SERPINA14 gene. The SERPINA14 mRNA abundance was quantified by real-time RT-PCR in intercaruncular endometrium at several time points during the estrous cycle and early pregnancy. Highest levels were found at estrus, followed by a dramatic decrease and a moderate expression during the luteal phase. Transcript levels were higher in pregnant endometrium compared with controls at Day 18. At estrus, immunoreactive protein was localized in deep glandular epithelium, and Western blotting concomitantly showed the 52-kDa form in uterine flushings. SERPINA14 mRNA was significantly upregulated in glandular endometrial cells in vitro after stimulation with estradiol-17beta and progesterone, but not after interferon-tau treatment. Our results clearly demonstrate that SERPINA14 appears distinctly in bovine endometrium during the estrus phase. A supporting role toward providing a well-prepared endometrial environment for passing gametes, especially sperm, is assumed.

  7. Palmatine inhibits TRIF-dependent NF-κB pathway against inflammation induced by LPS in goat endometrial epithelial cells.

    PubMed

    Yan, Baoqi; Wang, Dongsheng; Dong, Shuwei; Cheng, Zhangrui; Na, Lidong; Sang, Mengqi; Yang, Hongzao; Yang, Zhiqiang; Zhang, Shidong; Yan, Zuoting

    2017-04-01

    Palmatine, a natural pharmaceutical drug, possesses many biological activities. But its clinical application is rarely reported in the veterinary medicine. The aim of this study was to investigate the anti-inflammatory effects of palmatine on lipopolysaccharide (LPS)-induced inflammation in goat endometrial epithelial cells (gEECs), and the possible molecular mechanisms. Palmatine cell toxicity was determined by MTT assay, and the production of inflammatory cytokine in the cultured medium was measured with ELISA, qRT-PCR and Western blotting. Our results showed that palmatine treatment inhibited the release of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, nitric oxide (NO), matrix metalloproteinase (MMP)-9 and MMP-2. Furthermore, palmatine enhanced the secretion of prostaglandins E2 (PGE2) and IL-10. Palmatine significantly down-regulated the expression of Toll-like receptor 4 (TLR4), cluster of differentiation 14 (CD14), Toll/interleukin 1 receptor (TIR)-domain-containing adaptor protein inducing interferon-β (TICAM, TRIF) and nuclear factor-κB (NF-κB) in LPS stimulated gEECs, but did not alter the production of MyD88. In conclusion, palmatine inhibits TRIF-dependent NF-κB pathway to reduce LPS-induced inflammatory responses in goat endometrial epithelial cells.

  8. Verbal redundancy aids memory for filmed entertainment dialogue.

    PubMed

    Hinkin, Michael P; Harris, Richard J; Miranda, Andrew T

    2014-01-01

    Three studies investigated the effects of presentation modality and redundancy of verbal content on recognition memory for entertainment film dialogue. U.S. participants watched two brief movie clips and afterward answered multiple-choice questions about information from the dialogue. Experiment 1 compared recognition memory for spoken dialogue in the native language (English) with subtitles in English, French, or no subtitles. Experiment 2 compared memory for material in English subtitles with spoken dialogue in English, French, or no sound. Experiment 3 examined three control conditions with no spoken or captioned material in the native language. All participants watched the same video clips and answered the same questions. Performance was consistently good whenever English dialogue appeared in either the subtitles or sound, and best of all when it appeared in both, supporting the facilitation of verbal redundancy. Performance was also better when English was only in the subtitles than when it was only spoken. Unexpectedly, sound or subtitles in an unfamiliar language (French) modestly improved performance, as long as there was also a familiar channel. Results extend multimedia research on verbal redundancy for expository material to verbal information in entertainment media.

  9. In vitro differentiation of bone marrow mesenchymal stem cells into endometrial epithelial cells in mouse: a proteomic analysis

    PubMed Central

    Cong, Qing; Li, Bin; Wang, Yisheng; Zhang, Wenbi; Cheng, Mingjun; Wu, Zhiyong; Zhang, Xiaoyan; Jiang, Wei; Xu, Congjian

    2014-01-01

    Objective: Mouse bone marrow mesenchymal stem cells (BMSCs) have been demonstrated to differentiate into female endometrial epithelial cells (EECs) in vivo. Our previous studies demonstrated that BMSCs can differentiate in the direction of EECs when co-cultured with endometrial stromal cells in vitro. Here, we obtain and analyse differential proteins and their relevant pathways in the process of BMSCs differentiating into EECs by isobaric tags for relative and absolute quantitation (iTRAQ) proteomic analysis. Methods: A 0.4-μm pore size indirect co-culture system was established with female mice endometrial stromal cells (EStCs) restricted in the upper Transwell chamber and BMSCs in the lower well plate. After indirect co-culture for several days, the BMSCs were revealed to progressively differentiate towards EECs in vitro. Then, four groups were divided according to different co-culture days with single culture groups of BMSCs as controls. Proteins were detected using iTRAQ based on 2DLC-ESI-MS/MS and data were analysed by bioinformatics. Results: A total number of 311 proteins were detected, of which 210 proteins were identified with relative quantitation. Among them, 107 proteins were differentially expressed with a 1.2-fold change as the benchmark, with 61 up-regulated and 46 down-regulated proteins. Differential proteins CK19 and CK8 were epithelial markers and upregulated. Stromal marker vimentin were downregulated. Top canonical pathways was “remodeling of epithelial adhesions junctions” and “actin cytoskeleton signaling”. Top networks was “cell-to-cell signaling and interaction, tissue development and cellular movement” regulated by ERK/MAPK and α-catenin. Conclusion: To the best of our knowledge, this is the first preliminary study of differential protein expression in the differentiation process of BMSCs into EECs in vitro. We further elucidated BMSCs differentiated in the direction of EECs. In addition, ERK/MAPK and α-catenin played

  10. 75 FR 26938 - Notice of Vacancies on the U.S. Section of the U.S.-Iraq Business Dialogue

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-13

    ... Dialogue or Dialogue) in July 2006. This notice announces ten open membership opportunities for... currently seeking candidates for ten membership positions on the U.S. Section of the Dialogue....

  11. The oncofetal protein IMP3: a novel biomarker for endometrial serous carcinoma.

    PubMed

    Zheng, Wenxin; Yi, Xiaofang; Fadare, Oluwole; Liang, Sharon X; Martel, Maritza; Schwartz, Peter E; Jiang, Zhong

    2008-02-01

    Insulin-like growth factor II mRNA-binding protein 3 (IMP3) is an oncofetal protein highly expressed in fetal tissue and malignant tumors but rarely found in adult benign tissues. The aim of this study is to determine the expression of IMP3 in benign endometrium, endometrial cancer, and its precursor lesions, trying to see whether IMP3 has any diagnostic usage. Two hundred ninety-eight endometrial samples were examined for IMP3 expression by immunohistochemistry. These included benign endometrium (n=68), atypical hyperplasia or endometrial intraepithelial neoplasia (n=35), endometrial glandular dysplasia (n=21), endometrial intraepithelial carcinoma (n=18), endometrioid carcinoma (n=70), mucinous carcinoma (n=8), serous carcinoma (n=51), clear cell carcinoma (n=12), and other malignancies (n=15). Maturational patterns in the 68 benign endometrial samples included atrophic (n=12), proliferative (n=18), secretory (n=14), menstrual (n=8), and gestational (n=16). Most of the carcinomas were histologically pure; where mixed, the second component constituted <10% of the total tumor volume. The extent and intensity of IMP3 expression was semiquantitatively determined and scored for all samples. A renal cell carcinoma with known IMP3 expression was used as positive control for each immunohistochemistry run. Among the malignant cases, IMP3 expression was predominantly found in endometrial serous carcinoma and its putative precursor lesions, with 3 (14%) of 21 endometrial glandular dysplasia, 16 (89%) of 18 serous endometrial intraepithelial carcinoma, and 48 (94%) of 51 serous carcinomas (P<0.001). In contrast, the frequency of IMP3 expression was significantly lesser in nonserous malignancies with 0 (0%) of 35, 5 (7%) of 70, 0 (0%) of 8, 3 (25%) of 12, and 5 (33%) of 15 positive expression rates in atypical hyperplasia or endometrial intraepithelial neoplasia, endometrioid, mucinous, clear cell carcinomas, and other malignancies, respectively. The IMP3 staining was

  12. Use of levonorgestrel-releasing intrauterine system in the prevention and treatment of endometrial hyperplasia.

    PubMed

    Ewies, Ayman A A; Alfhaily, Fadi

    2012-11-01

    Endometrial hyperplasia is a commonly seen gynecological condition that affects women of all age groups. Whereas hysterectomy is the most preferred treatment option for complex endometrial hyperplasia with atypia, there is no consensus regarding the first-line management of women with hyperplasia without cytological atypia. Oral progestogen therapy was used with some success. Nonetheless, it may be plausible to argue that women with endometrial hyperplasia need continuous treatment and high level of compliance to ensure complete regression, which may not be guaranteed with oral therapy. Observational studies suggested that levonorgestrel-releasing intrauterine system (LNG-IUS) has been successfully used to treat endometrial hyperplasia without cytological atypia and selected cases of atypical endometrial hyperplasia. Furthermore, there is strong evidence from randomized controlled trials that LNG-IUS prevents the development of endometrial hyperplasia in exogenous estrogen users; however, its protective role and safety in tamoxifen-treated breast cancer survivors remain uncertain. This article evaluates the current evidence for the use of LNG-IUS, releasing 20 μg of LNG per day, in the prevention and treatment of endometrial hyperplasia.

  13. Primary sources of pelvic serous cancer in patients with endometrial intraepithelial carcinoma.

    PubMed

    Jia, Lin; Yuan, Zeng; Wang, Yiying; Cragun, Janiel M; Kong, Beihua; Zheng, Wenxin

    2015-01-01

    Serous endometrial intraepithelial carcinoma is often associated with extrauterine disease. It is currently unclear where does the extrauterine disease come from. This study addressed this issue. A total of 135 samples from 21 serous endometrial intraepithelial carcinoma patients were studied. Cellular lineage relationships between intrauterine and extrauterine serous carcinomas were determined by TP53-mutation analysis and correlated to the clinicopathologic features. There were three conditions contributing the extrauterine disease: metastasis from serous endometrial intraepithelial carcinoma (n=10) showed identical TP53 mutation between intrauterine lesions and extrauterine disease, cases of adnexal origin (n=5) had discordant TP53 mutations, and the mixed cellular origin cases (n=6) with both identical and discordant mutation status. Patients with extrauterine disease from serous endometrial intraepithelial carcinoma metastasis typically had small tumor masses (<2 cm) in extrauterine sites and without finding of serous tubal intraepithelial carcinoma, while extrauterine disease with adnexal or tubal origin commonly had larger tumor masses in extrauterine sites including ovary and omentum and serous tubal intraepithelial carcinoma. The majority of extrauterine diseases associated with serous endometrial intraepithelial carcinoma are metastasized from the endometrium. Serous endometrial intraepithelial carcinoma is frequently associated with serous cancers of adnexal or tubal origin, indicating that endometrial and adnexal or tubal serous cancers may share similar etiologies. TP53-mutation analysis provides a strong linkage for cellular lineage analysis. Tumor size in extrauterine disease and presence of serous tubal intraepithelial carcinoma or not are useful clinicopathologic features to determine primary cancer site, which helps in clinical management.

  14. Tubal ligation and risk of endometrial cancer: Findings from the Women’s Health Initiative

    PubMed Central

    Winer, Ira; Lehman, Amy; Wactawski-Wende, Jean; Robinson, Randall; Simon, Michael; Cote, Michele

    2015-01-01

    Objective Bilateral tubal ligation (BTL) is a common form of birth control in the United States. There is limited, contradictory data examining BTL and the risk of endometrial cancer and none examining type I and type II cancers separately. We investigated the association between BTL and endometrial cancer risk utilizing the Women’s Health Initiative (WHI) Observational (OS) and Dietary Modification (DM) Studies. Methods Demographic information and history of BTL were obtained from the baseline questionnaires from 76,483 WHI participants in the OS and DM. Univariable and multivariable models were used to examine the association of BTL with type I and type II endometrial cancers. Results 1,137 women were diagnosed with incident endometrial cancer (972 type I and 128 type II) over a mean follow-up of 11.3 years. Overall, 14,499 women (19%) had undergone BTL. There were no statistically significant associations noted between BTL or age at BTL for type I or type II cancers. Conclusion We examined the largest patient cohort to date in an effort to determine the impact of BTL on endometrial cancer risk. In the WHI trial we observed no overall effect of BTL on the risk of type I or type II endometrial cancer, suggesting that patients undergoing this popular birth-control method likely do not have an associated change in their baseline risk for endometrial cancer. PMID:26825831

  15. Median Survival Time of Endometrial Cancer Patients with Lymphovascular Invasion at the Hospital Universiti Sains Malaysia

    PubMed Central

    Asyikeen, Wan Adnan Wan Nor; Siti-Azrin, Ab Hamid; Jalil, Nur Asyilla Che; Zin, Anani Aila Mat; Othman, Nor Hayati

    2016-01-01

    Background Endometrial cancer is the most common gynaecologic malignancy among females worldwide. The purpose of this study was to determine the median survival time of endometrial cancer patients at the Hospital Universiti Sains Malaysia (USM). Methods A list of 121 endometrial cancer cases registered at Hospital USM between 2000 until 2011 was retrospectively reviewed. The survival time of the endometrial cancer patients was estimated by Kaplan-Meier survival analysis. Log-rank tests were performed to compare the survival of the patients based on socio-demographics and clinical presentation. Results Only 108 patients, 87.0%, were included who were of Malay ethnicity. Previous history included menopause in 67.6% of patients and diabetes mellitus in 39.8% of patients; additionally, 63.4% of patients were nulliparous. Tumour staging was as follows: 24.5% stage I, 10.8% stage II, 26.5% stage III and 38.2% stage IV. The overall median survival time of the endometrial cancer patients was 70.20 months (95% confidence interval (CI): 51.79, 88.61). The significant factors were age, the presence of lymphovascular invasion and treatment received. Conclusion The overall survival of endometrial cancer was low. A prospective study needs to be carried out to discover more effective and accurate tests for the early detection of endometrial cancer. PMID:28090178

  16. Antinidatory effect of luteal phase administration of mifepristone (RU486) is associated with changes in endometrial prostaglandins during the implantation window.

    PubMed

    Nayak, N R; Sengupta, J; Ghosh, D

    1998-08-01

    Luteal phase administration of mifepristone provides a significant degree of pregnancy protection to monkeys and women. Among several proposed mediators of the antinidatory action of luteal phase mifepristone, prostaglandins (PG) at the endometrial level appear important, and was examined in the present study using the rhesus monkey as the primate model. To this end, the concentrations of PGE2 and PGF2 alpha in endometrium and the profiles of cyclooxygenase (COX) and 15-hydroxy prostaglandin dehydrogenase (PGDH) were examined in untreated control animals, in animals subjected to mifepristone treatment (2 mg/day) alone or along with diclofenac (25 mg/day), or along with a PGE1 analog (100 micrograms misoprostol), in animals subjected to diclofenac alone treatment, and in animals treated with misoprostol alone on cycle days 16, 17, and 18. Tissue samples were collected on day 20 of treatment cycles from animals with discernible corpora lutea. Early luteal phase treatment with diclofenac did not result in any remarkable change in endometrial prostaglandin concentrations, however, there was an increase in the profile of COX. Animals exposed to misoprostol in the prereceptive stage, on the other hand, exhibited decreased expression of endometrial COX. The concentrations of PGF2 alpha and PGE2, as well as the ratios of PGF2 alpha to PGE2 concentrations, were increased along with a decrease in COX and PGD in endometrial samples following luteal phase mifepristone treatment. Although the underlying cellular mechanism of regulation of COX and PGDH in mifepistone-treated endometrium remains to be examined, the decrease in PG catabolism through low PGDH may contribute to the increased PG and high ratio of PGF2 alpha to PGE2 in mifepristone-exposed endometrium. It is plausible that mifepristone action on endometrial cells is mediated by an altered ratio of PGF2 alpha to PGE2. Furthermore, it appears that the regulation of PG milieu by COX and PGDH activities in reproductive

  17. LeftyA decreases Actin Polymerization and Stiffness in Human Endometrial Cancer Cells

    PubMed Central

    Salker, Madhuri S.; Schierbaum, Nicolas; Alowayed, Nour; Singh, Yogesh; Mack, Andreas F.; Stournaras, Christos; Schäffer, Tilman E.; Lang, Florian

    2016-01-01

    LeftyA, a cytokine regulating stemness and embryonic differentiation, down-regulates cell proliferation and migration. Cell proliferation and motility require actin reorganization, which is under control of ras-related C3 botulinum toxin substrate 1 (Rac1) and p21 protein-activated kinase 1 (PAK1). The present study explored whether LeftyA modifies actin cytoskeleton, shape and stiffness of Ishikawa cells, a well differentiated endometrial carcinoma cell line. The effect of LeftyA on globular over filamentous actin ratio was determined utilizing Western blotting and flow cytometry. Rac1 and PAK1 transcript levels were measured by qRT-PCR as well as active Rac1 and PAK1 by immunoblotting. Cell stiffness (quantified by the elastic modulus), cell surface area and cell volume were studied by atomic force microscopy (AFM). As a result, 2 hours treatment with LeftyA (25 ng/ml) significantly decreased Rac1 and PAK1 transcript levels and activity, depolymerized actin, and decreased cell stiffness, surface area and volume. The effect of LeftyA on actin polymerization was mimicked by pharmacological inhibition of Rac1 and PAK1. In the presence of the Rac1 or PAK1 inhibitor LeftyA did not lead to significant further actin depolymerization. In conclusion, LeftyA leads to disruption of Rac1 and Pak1 activity with subsequent actin depolymerization, cell softening and cell shrinkage. PMID:27404958

  18. Evidence of a Causal Association Between Insulinemia and Endometrial Cancer: A Mendelian Randomization Analysis

    PubMed Central

    Nead, Kevin T.; Sharp, Stephen J.; Thompson, Deborah J.; Painter, Jodie N.; Savage, David B.; Semple, Robert K.; Barker, Adam; Perry, John R. B.; Attia, John; Dunning, Alison M.; Easton, Douglas F.; Holliday, Elizabeth; Lotta, Luca A.; O’Mara, Tracy; McEvoy, Mark; Pharoah, Paul D. P.; Scott, Rodney J.; Spurdle, Amanda B.; Langenberg, Claudia; Wareham, Nicholas J.

    2015-01-01

    Background: Insulinemia and type 2 diabetes (T2D) have been associated with endometrial cancer risk in numerous observational studies. However, the causality of these associations is uncertain. Here we use a Mendelian randomization (MR) approach to assess whether insulinemia and T2D are causally associated with endometrial cancer. Methods: We used single nucleotide polymorphisms (SNPs) associated with T2D (49 variants), fasting glucose (36 variants), fasting insulin (18 variants), early insulin secretion (17 variants), and body mass index (BMI) (32 variants) as instrumental variables in MR analyses. We calculated MR estimates for each risk factor with endometrial cancer using an inverse-variance weighted method with SNP-endometrial cancer associations from 1287 case patients and 8273 control participants. Results: Genetically predicted higher fasting insulin levels were associated with greater risk of endometrial cancer (odds ratio [OR] per standard deviation = 2.34, 95% confidence internal [CI] = 1.06 to 5.14, P = .03). Consistently, genetically predicted higher 30-minute postchallenge insulin levels were also associated with endometrial cancer risk (OR = 1.40, 95% CI = 1.12 to 1.76, P = .003). We observed no associations between genetic risk of type 2 diabetes (OR = 0.91, 95% CI = 0.79 to 1.04, P = .16) or higher fasting glucose (OR = 1.00, 95% CI = 0.67 to 1.50, P = .99) and endometrial cancer. In contrast, endometrial cancer risk was higher in individuals with genetically predicted higher BMI (OR = 3.86, 95% CI = 2.24 to 6.64, P = 1.2x10-6). Conclusion: This study provides evidence to support a causal association of higher insulin levels, independently of BMI, with endometrial cancer risk. PMID:26134033

  19. Expression of MIF and c-erbB-2 in endometrial cancer.

    PubMed

    Xiao, Wei; Dong, Xiujuan; Zhao, Honghui; Han, Shiyu; Nie, Ruixue; Zhang, Xiahua; An, Ruifang

    2016-05-01

    The aim of the present study was to investigate the expression of c-erbB-2 and macrophage migration inhibitory factor (MIF) in endometrial cancer and to elucidate the significance of the early diagnosis and prognosis of endometrial cancer. The gene copy number of c‑erbB‑2 and MIF was characterized by reverse transcription quantitative polymerase chain reaction and the reactivity was assessed by immunohistochemistry in 70 patients using a polyclonal antibody, and evaluated semiquantitatively according to the percentage of cells demonstrating membranous or diffuse cytoplasmic staining. A correlation between age, tumor stage, grade, myometrial invasion and lymph node metastasis was observed. The mRNA expression of c‑erbB‑2 and MIF was high in endometrial carcinoma. The positive expression rate of MIF protein in normal endometrium, atypical hyperplasia and endometrial carcinoma significantly increased along with the degree of aggravation of the disease by 20 (3/15), 45 (9/20) and 70% (35/50), respectively. The positive expression of MIF and c‑erbB‑2 was highest in endometrial cancer and a significantly higher level of protein was observed in tumors at stage I, stage G1, with a depth of myometrial invasion <0.4 cm and no lymph node metastasis. The protein expression of c‑erbB‑2 in endometrial cancer was higher in tumors at the G2‑3 phase, clinical stage III‑IV, lymph node metastasis, and had no association with the depth of myometrial invasion and age. MIF and c‑erbB‑2 were correlated with the occurrence and the development of endometrial cancer, and thus can be used for the early diagnosis and prognosis of endometrial cancer. The present study laid the foundation for identifying new treatments for endometrial cancer.

  20. Presence of HHV-6A in Endometrial Epithelial Cells from Women with Primary Unexplained Infertility

    PubMed Central

    Bortolotti, Daria; Lo Monte, Giuseppe; Caselli, Elisabetta; Bolzani, Silvia; Rotola, Antonella; Di Luca, Dario; Rizzo, Roberta

    2016-01-01

    To elucidate the roles of human herpesvirus (HHV)-6 primary unexplained infertile women, a prospective randomized study was conducted on a cohort of primary unexplained infertile women and a cohort of control women, with at least one successful pregnancy. HHV-6 DNA was analyzed and the percentage and immune-phenotype of resident endometrial Natural Killer (NK) cells, as the first line of defense towards viral infections, was evaluated in endometrial biopsies. Cytokine levels in uterine flushing samples were analyzed. HHV-6A DNA was found in 43% of endometrial biopsies from primary unexplained infertile women, but not in control women. On the contrary, HHV-6B DNA was absent in endometrial biopsies, but present in PBMCs of both cohorts. Endometrial NK cells presented a different distribution in infertile women with HHV6-A infection compared with infertile women without HHV6-A infection. Notably, we observed a lower percentage of endometrial specific CD56brightCD16- NK cells. We observed an enhanced HHV-6A-specific endometrial NK cell response in HHV-6A positive infertile women, with a marked increase in the number of endometrial NK cells activating towards HHV-6A infected cells. The analysis of uterine flushing samples showed an increase in IL-10 levels and a decrease of IFN-gamma concentrations in infertile women with HHV6-A infection. Our study indicates, for the first time, that HHV-6A infection might be an important factor in female unexplained infertility development, with a possible role in modifying endometrial NK cells immune profile and ability to sustain a successful pregnancy. PMID:27367597

  1. Persuasive Dialogue Based on a Narrative Theory: An ECA Implementation

    NASA Astrophysics Data System (ADS)

    Cavazza, Marc; Smith, Cameron; Charlton, Daniel; Crook, Nigel; Boye, Johan; Pulman, Stephen; Moilanen, Karo; Pizzi, David; de La Camara, Raul Santos; Turunen, Markku

    Embodied Conversational Agents (ECA) are poised to constitute a specific category within persuasive systems, in particular through their ability to support affective dialogue. One possible approach consists in using ECA as virtual coaches or personal assistants and to make persuasion part of a dialogue game implementing specific argumentation or negotiation features. In this paper, we explore an alternative framework, which emerges from the long-term development of ECA as "Companions" supporting free conversation with the user, rather than task-oriented dialogue. Our system aims at influencing user attitudes as part of free conversation, albeit on a limited set of topics. We describe the implementation of a Companion ECA to which the user reports on his working day, and which can assess the user's emotional attitude towards daily events in the office, trying to influence such attitude using affective strategies derived from a narrative model. This discussion is illustrated through examples from a first fully-implemented prototype.

  2. Development of critically reflective dialogues in communities of health professionals.

    PubMed

    de Groot, Esther; Endedijk, Maaike; Jaarsma, Debbie; van Beukelen, Peter; Simons, Robert-Jan

    2013-10-01

    Critically reflective dialogues (CRD) are important for knowledge sharing and creating meaning in communities. CRD includes different aspects: being open about mistakes, critical opinion sharing, asking for and giving feedback, experimentation, challenging groupthink and research utilisation. In this article we explore whether CRD aspects change over time, through a study of two dialogues each from six different communities of veterinary health professionals. Change was studied from the perspective of observations, through analysing transcripts of dialogues, and from the perspective of community members' perceptions, through an evaluative discussion with members. The results showed that some communities became more open about mistakes, a finding that is related to an increase in trust. Other observed aspects of CRD seemed to be fairly stable over time. Community members perceived research utilisation and asking for and giving feedback to have been increased. From an analysis of perceptions of the community members it emerged that limited interaction could be associated with the epistemological conceptions of community members.

  3. Nursing homes as learning environments: the impact of professional dialogue.

    PubMed

    Skaalvik, Mari Wolff; Normann, Ketil; Henriksen, Nils

    2012-05-01

    Nursing students' clinical experiences are important with respect to their impact on attitudes towards care for older people and preferences for future workplaces. The purpose of this paper is to explore how professional dialogue has an impact on nursing students' clinical learning and professional development in nursing homes. A qualitative design based on field work, field notes and qualitative research interviews was employed with 12 third year nursing students undergoing clinical practise in three nursing homes in Norway. The nursing students who participated in this study displayed positive attitudes towards older people. However, their experiences and perceptions of the learning environment in the nursing homes, varied. The nursing students expressed that a positive learning environment included participation in nursing care and professional dialogue to support their learning process and outcomes. Their primary wish was to develop their knowledge about care for older people through participation and dialogue as critical and reflective processes in a community of practise.

  4. Dysregulation of In Vitro Decidualization of Human Endometrial Stromal Cells by Insulin via Transcriptional Inhibition of Forkhead Box Protein O1

    PubMed Central

    Babayeva, Shabnam; Salamon, Daniel; Rethi, Bence; Gidlöf, Sebastian; Hirschberg, Angelica Lindén

    2017-01-01

    Insulin resistance and compensatory hyperinsulinemia are characteristic features of obesity and polycystic ovary syndrome, and both are associated with reduced fertility and implantation. There is little knowledge about the effect of insulin on the decidualization process and previous findings are contradictory. We investigated the effect of insulin on the regulation of forkhead box protein O1 (FOXO1), one of the most important transcription factors during decidualization. Endometrial stromal cells were isolated from six healthy, regularly menstruating women and decidualized in vitro. Gene expression levels of six putative FOXO1 target genes (including insulin-like growth factor binding protein-1 (IGFBP1) and prolactin (PRL)) were measured with Real-Time PCR following FOXO1 inhibition or insulin treatment. PI3K inhibition was used to identify the possible mechanism behind regulation. Subcellular localization of FOXO1 was analyzed with immunofluorescence. All the genes (IGFBP1, CTGF, INSR, DCN, LEFTY2), except prolactin, were evaluated as FOXO1 target genes in decidualizing stromal cells. Insulin caused a significant dose-dependent inhibition of the verified FOXO1 target genes. It was also demonstrated that insulin regulated FOXO1 target genes by transcriptional inactivation and nuclear export of FOXO1 via PI3K pathway. However, insulin did not inhibit the morphological transformation of endometrial stromal cells via transcriptional inactivation of FOXO1. This study provides new insights on the action of insulin on the endometrium via regulation of FOXO1. It is suggested that hyperinsulinemia results in dysregulation of a high number of FOXO1 controlled genes that may contribute to endometrial dysfunction and reproductive failure. Our findings may illuminate possible reasons for unexplained infertility. PMID:28135285

  5. Biomarkers of progestin therapy resistance and endometrial hyperplasia progression

    PubMed Central

    Upson, Kristen; Allison, Kimberly H.; Reed, Susan D.; Jordan, Carolyn D.; Newton, Katherine M.; Swisher, Elizabeth M.; Doherty, Jennifer A.; Garcia, Rochelle L.

    2012-01-01

    Objective To identify biomarkers associated with progestin therapy resistance and persistence/progression of endometrial hyperplasia. Study Design We performed a nested case-control study among women with complex (n=73) and atypical (n=41) hyperplasia treated with oral progestin, followed 2–6 months for persistence/progression. We evaluated index endometrial protein expression for progesterone receptors A (PRA) and B (PRB), PTEN, Pax-2 and Bcl-2. Odds ratios and 95% confidence intervals were estimated. Results Among women with atypical hyperplasia, high PRB expression was associated with 90% decreased risk of persistence/progression (95% CI: 0.01–0.8). High expression of PRA and PRB suggested decreased risk of persistence/ progression (OR=0.1, 95% CI: 0.02–1.0). These findings were not observed among women with complex hyperplasia. No associations were found with PTEN, Pax-2, and Bcl-2 protein expression. Conclusions PRB expression shows promise as a biomarker of progestin response. Further research is warranted to understand how PRB expression may guide treatment decisions. PMID:22727345

  6. Assessing endometrial hyperplasia and carcinoma treated with progestin therapy.

    PubMed

    Mentrikoski, Mark J; Shah, Akeesha A; Hanley, Krisztina Z; Atkins, Kristen A

    2012-10-01

    The effects of increased amounts of progesterone on the endometrium, including such features as eosinophilic cytoplasmic metaplasia, glandular atrophy, and decidualized stroma, are well-known among surgical pathologists. These changes are typically seen as secondary effects of pregnancy or exogenous hormone therapy for birth control purposes or abnormal bleeding. Treatment with progesterone has become a viable alternative to hysterectomy in some patients with complex atypical hyperplasia (CAH) and well-differentiated endometrial carcinoma (WDC), especially those who are poor surgical candidates or those wishing to preserve fertility. To date, only 1 study has specifically examined the effects of progestin therapy on patients with a previous diagnosis of CAH or WDC. That study proposed a classification scheme for the assessment of treated CAH and WDC. The authors concluded that after 6 months of treatment, endometrial biopsy findings of persistent cytologic atypia and architectural abnormalities were associated with treatment failure. This current study aims to assess the previously proposed criteria in a cohort of 30 patients (18 with a diagnosis of CAH and 12 with a diagnosis of WDC), and determine the usefulness of these criteria in clinical practice. Our study confirms that cytologic atypia after 6 months of therapy is strongly associated with treatment failure, and should be an indication to pursue definitive surgical treatment in these patients.

  7. Endometrial cancer. Prevention, detection, management, and follow up.

    PubMed Central

    Elit, L.

    2000-01-01

    OBJECTIVE: To review risk factors for uterine cancer; to discuss strategies for detecting uterine cancer; to outline prognostic factors and treatment; and to review the role of follow up for patients who have completed primary therapy. QUALITY OF EVIDENCE: MEDLINE was searched from January 1996 to June 1998 using the terms endometrial neoplasms, estrogen replacement therapy, hormone replacement therapy, tamoxifen, and screening. Only English language articles were reviewed. Study types included reviews. Bibliographies of articles found were searched for further relevant titles. Causation literature is available from well conducted cohort trials. Treatment recommendations are based in part on prognostic information and a few randomized controlled trials. MAIN MESSAGE: Risk factors, both intrinsic and extrinsic, are associated with uterine cancer. Family physicians have a role in preventing disease by ensuring that all women with uteri in situ using hormone replacement therapy (HRT) have progesterone therapy as part of the HRT regimen. Detection is crucial; abnormal uterine bleeding or undiagnosed postmenopausal bleeding warrants investigation with endometrial biopsy. The goal of surgery is to remove the uterus and ovaries and identify factors that make the disease at high risk of recurrence. Although adjuvant radiation therapy does not prolong survival, it does alter the pattern of disease recurrence. The goal of follow up after primary therapy is to identify recurrent disease while it is still curable. CONCLUSIONS: Family physicians play an important role in preventing uterine cancer, initiating early diagnosis of disease, and in the future, might be more actively involved in caring for patients following primary therapy. PMID:10790821

  8. Glycan profiling of endometrial cancers using lectin microarray.

    PubMed

    Nishijima, Yoshihiro; Toyoda, Masashi; Yamazaki-Inoue, Mayu; Sugiyama, Taro; Miyazawa, Masaki; Muramatsu, Toshinari; Nakamura, Kyoko; Narimatsu, Hisashi; Umezawa, Akihiro; Mikami, Mikio

    2012-10-01

    Cell surface glycans change during the process of malignant transformation. To characterize and distinguish endometrial cancer and endometrium, we performed glycan profiling using an emerging modern technology, lectin microarray analysis. The three cell lines, two from endometrial cancers [well-differentiated type (G1) and poorly differentiated type (G3)] and one from normal endometrium, were successfully categorized into three independent groups by 45 lectins. Furthermore, in cancer cells, a clear difference between G1 and G3 type was observed for the glycans recognized with six lectins, Ulex europaeus agglutinin I (UEA-I), Sambucus sieboldiana agglutinin (SSA), Sambucus nigra agglutinin (SNA), Trichosanthes japonica agglutinin I (TJA-I), Amaranthus caudatus agglutinin (ACA), and Bauhinia purpurea lectin (BPL). The lectin microarray analysis using G3 type tissues demonstrated that stage I and stage III or IV were distinguished depending on signal pattern of three lectins, Dolichos biflorus agglutinin (DBA), BPL, and ACA. In addition, the analysis of the glycans on the ovarian cancer cells showed that only anticancer drug-sensitive cell lines had almost no activities to specific three lectins. Glycan profiling by the lectin microarray may be used to assess the characteristics of tumors and potentially to predict the success of chemotherapy treatment.

  9. Polymorphisms in cyclooxygenase-2 gene in endometrial cancer patients.

    PubMed

    Torricelli, Federica; Mandato, Vincenzo Dario; Farnetti, Enrico; Abrate, Martino; Casali, Bruno; Ciarlini, Gino; Pirillo, Debora; Gelli, Maria Carolina; Costagliola, Luigi; Nicoli, Davide; Palomba, Stefano; La Sala, Giovanni Battista

    2015-09-01

    The enzyme cyclooxygenase 2 is an inducible enzyme expressed at sites of inflammation and in a variety of malignant solid tumors such as endometrial cancer (EC). In EC patients, its over-expression is correlated with progressive disease and poor prognosis. The expression is encoded by a polymorphic gene, called PTGS2. The aim of the current study was to test the hypothesis that rs5275 polymorphism of PTGS2 influence the prognosis of EC patients. This paper is a retrospective cohort study. Clinical and pathological data were extrapolated and genotypes were assessed on formalin-fixed and paraffin-embedded non-tumor tissues. A total of 159 type I EC patients were included in the final analysis. Univariate analysis indicated that patients with rs5275 genotype CC have a lower risk to develop a grade (G) 2-3 endometrial cancer. rs5275 effect on EC grading was confirmed by multivariate analysis also after data adjusting for age, BMI, parity, hypertension, and diabetes. Adjusted odds ratio (OR) confirmed that patients with rs5275 genotype CC have a risk 80 % lower (OR = 0.20, P = 0.009) to develop a G2 and/or G3 EC in comparison with patients with TT or TC genotype. Differentiation of the type 1 EC is significantly and independently influenced by rs5275 polymorphism. rs5275 CC patients have a lower risk to present a G2-G3 EC.

  10. Distinction between endometrial and endocervical adenocarcinoma: an immunohistochemical study.

    PubMed

    Castrillon, Diego H; Lee, Kenneth R; Nucci, Marisa R

    2002-01-01

    We investigated the possibility of distinguishing between primary endometrial and endocervical adenocarcinomas by using a panel of immunohistochemical stains, which included vimentin (VIM), carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), and cytokeratins 7 and 20 (CK7 and CK20). Twenty-nine endocervical adenocarcinomas (CCAs) and 30 endometrial adenocarcinomas (EMCAs) including cases with overlapping histologic features (CCAs with endometrioid differentiation [15/29] and EMCAs with mucinous differentiation [16/30]) were evaluated. Most EMCAs (29/30, 97%) were VIM positive, whereas only 2/29 (7%) CCAs were VIM positive. The great majority of EMCAs (28/30) and all 29 CCAs were CK7 positive, whereas all 30 EMCAs and 27/29 CCAs were negative for CK20. CEA positivity was more common in CCAs (18/29, 62%) than in EMCAs (8/30, 27%). EMA positivity was present in all 30 EMCAs and in 26 of 29 (90%) CCAs. We conclude that VIM and CEA are useful immunohistochemical markers in distinguishing EMCAs and CCAs, but CK7, CK20, and EMA are not useful in this distinction.

  11. Endometrial ablation using SideFire laser fiber

    NASA Astrophysics Data System (ADS)

    Everett, Royice B.

    1996-05-01

    The first successful report using the neodymium:yttrium-aluminum-garnet (Nd:YAG) Laser to control hypermenorrhea was reported in 1981. Variations on the treatment technique have been attempted to improve the amenorrhea rate. Reports using the Nd:YAG laser with the blanching or non-touch technique seem to result in a better outcome and higher rate of total amenorrhea than using the dragging technique. Due to the report of improved rates of amenorrhea when using the blanching technique and the Nd:YAG laser, a fiber was developed to direct the laser energy at right angles to the axis of the fiber, therefore allowing a total treatment of the entire uterus in a perpendicular fashion. The theoretic benefit of this would be a more complete and predictable destruction of the endometrial lining, avoiding fluid overload by coagulating and sealing of the vessels and lymphatic. After a follow-up of 12 to 36 months, 56 of the 60 patients (93%) who underwent complete endometrial ablation with the SideFireTM technique had excellent results. Total absolute amenorrhea resulted in 50 patients (83%). Contrary to earlier reports, using the rollerball electrode, this procedure technique resulted in no decrease in results in younger patients. In conclusion, this seems to be a reasonable alternative which offers improved results when compared to previously available methods using electrosurgery or the Nd:YAG laser without the use of the SideFireTM device.

  12. Etiology and Effects of Ciomiphene on Cystic Endometrial Hyperplasia in the Miniature Pig

    DTIC Science & Technology

    1986-12-17

    luteinizing hormone , follicle stimulating hormone or prolactin (Spona et al., 1979). Disruption of the cyclic influence of estrogen and progesterone ...Effects of Estrogen and Progesterone on Endometrial Morphology ••••••••••••••••••.••••• Distribution of Endometrial Steroid Hormone ... Hormonal Profiles of CEH and non-CEH Sows •••••••••••••••••••••••••• Experiment III. Evaluation of Endometrial Estrogen and Progesterone Receptors

  13. Uterine leiomyomas: effects on architectural, cellular, and molecular determinants of endometrial receptivity.

    PubMed

    Makker, Annu; Goel, Madhu Mati

    2013-06-01

    Impaired endometrial receptivity is an important contributing factor to implantation failure. Uterine leiomyomas are widely prevalent steroid hormone-dependent benign tumors that act as a restraint to conception and successful outcome of pregnancies. Reports are available, which suggest that leiomyomas have negative influence on endometrial receptivity to blastocyst implantation. The aim of the present review is to provide a comprehensive picture of the current knowledge of the effect of uterine leiomyomas on the architectural, cellular, and molecular determinants of endometrial receptivity. Understanding the potential role of these factors will provide insight into the underlying mechanisms of leiomyoma-associated infertility and provide new areas for basic and translational research.

  14. Guiding dialogue in the transformation of teacher-student relationships.

    PubMed

    Gaines, S; Baldwin, D

    1996-01-01

    The National League for Nursing at its 1989 biennial convention resolved that nursing curricula be revised to reflect enriched caring practices through egalitarian teacher-student and teacher-to-teacher relationships that reflect cooperation and a sense of community. The distribution of power relationships between student and teacher, teacher and teacher, and teacher and administrator must be reconceptualized and realized before any significant change in nursing education's curriculum can occur. Revising curricula to incorporate such a change in teacher-student relationships begins with dialogue with teachers that is authentic. Authentic dialogue will cause examination and reexamination of assumptions and ideologies about teacher-student relationships.

  15. Is the positivity of estrogen receptor or progesterone receptor different between type 1 and type 2 endometrial cancer?

    PubMed Central

    Shen, Fang; Gao, Yifei; Ding, Jingxin; Chen, Qi

    2017-01-01

    Endometrial cancer is a major cancer in women and traditionally divided into type 1 and type 2. It is well known that type 2 endometrial cancer has a poor prognosis. Studies have suggested that estrogen receptor (ER) or progesterone receptor (PR) positive are positively associated with endometrial cancer survive. However whether the positivity of ER or PR is different between cancer types has not been investigated yet. In this retrospective study, the positivity of ER or PR was analysed in 1054 women with primary diagnosed endometrial cancer taking into account cancer types and menopausal status from the largest university teaching women's hospital in China. The positivity of ER or PR (over 90%) was significantly higher in type 1 compared to that in type 2 endometrial cancer (71% or 64%) in both premenopausal and postmenopausal women. There was no different in positivity of ER or PR in type 1 endometrial cancer between premenopausal and postmenopausal women. However, in type 2 endometrial cancer, the positivity of ER or PR in premenopausal women was significantly higher compared to that in postmenopausal women. Our data demonstrate that both ER and PR positivity are significantly higher in type 1 endometrial cancer (92%) compared to type 2 (72% ER positive, 65% PR positive). Menopausal status is not associated with the positivity of ER or PR in type 1 endometrial cancer. Our data may provide some novel insights why Asian women have better outcomes of endometrial cancer which was reported in the literature. PMID:27888807

  16. The levels of the sex hormones are not different between type 1 and type 2 endometrial cancer

    PubMed Central

    Wan, Jiayi; Gao, Yifei; Zeng, Ke; Yin, Yongxiang; Zhao, Min; Wei, Jia; Chen, Qi

    2016-01-01

    The involvement of hormonal factors in developing endometrial cancer is well documented. In particular, excess or unopposed estrogen is a major risk factor. Endometrial cancer is divided into estrogen-dependent and estrogen-independent types. Studies suggested that the subtypes of endometrial cancer share many common risk factors. Whether the levels of sex hormones differ between types 1 and 2 endometrial cancer has not been investigated. In this study, levels of estrogen, progesterone, testosterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) were investigated between type 1 and type 2 endometrial cancer taking into account menopausal status and parity. The sex hormones levels and estrogen and progesterone receptors were measured in 187 women with endometrial cancer. The levels of estradiol (E2), progesterone, testosterone, FSH and LH were not different between the subtypes of endometrial cancer regardless of menopausal status. In addition, the sex hormones were not different between patients of different party regardless of the menopausal status. The majority of type 1 (96%) and type 2 (82%) endometrial cancers were estrogen and progesterone receptor positive. Our data suggest that type 2 endometrial cancer is not completely estrogen independent, and type 1 and type 2 endometrial cancers may have a similar pathogenesis. PMID:28000774

  17. An Exploration of Reflective Dialogue between Student Teachers in Music and Their Cooperating Teachers

    ERIC Educational Resources Information Center

    Stegman, Sandra Frey

    2007-01-01

    The purpose of this study was to explore the content of reflective dialogues between student teachers in music and their cooperating teachers, as well as to understand the effects of reflective dialogue on professional development. I was guided in this analysis of 49 transcriptions of interviews and reflective dialogues between student teachers…

  18. Why Students Learn More From Dialogue-Than Monologue-Videos: Analyses of Peer Interactions

    ERIC Educational Resources Information Center

    Chi, Michelene T. H.; Kang, Seokmin; Yaghmourian, David L.

    2017-01-01

    In 2 separate studies, we found that college-age students learned more when they collaboratively watched tutorial dialogue-videos than lecture-style monologue-videos. In fact, they can learn as well as the tutees in the dialogue-videos. These results replicate similar findings in the literature showing the advantage of dialogue-videos even when…

  19. Creating Critical Conversations: Investigating the Utility of Socratic Dialogues in Elementary Social Studies Methods

    ERIC Educational Resources Information Center

    Buchanan, Lisa Brown

    2012-01-01

    This article explores the utility of Socratic dialogues in the elementary social studies methods course. Findings include preservice teachers' behaviors during dialogues, perceived strengths and challenges of using Socratic dialogues in teacher education, and the impact on student learning. Challenges and apprehensions encountered by the teacher…

  20. How Intergroup Dialogue Facilitators Understand Their Role in Promoting Student Development and Learning

    ERIC Educational Resources Information Center

    Quaye, Stephen John; Johnson, Matthew R.

    2016-01-01

    Intergroup dialogues are co-facilitated, face-to-face dialogues between two groups that have a history of conflict (for example, White people and people of color). Although researchers have explored the outcomes of these dialogues among students, little is known about the role of facilitators. Drawing from a case study of an intergroup dialogue…