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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. PMID:27533790

  2. Regulation of insulin-like growth factor signaling by metformin in endometrial cancer cells

    PubMed Central

    XIE, YA; WANG, JING-LU; JI, MEI; YUAN, ZHONG-FU; PENG, ZHENG; ZHANG, YI; WEN, JIAN-GUO; SHI, HUI-RONG

    2014-01-01

    Obesity, diabetes and insulin resistance are marked risk factors that promote the development of type I endometrial cancer. Previous studies have demonstrated that insulin-like growth factor 1 (IGF-1) and IGF-2 promote cell proliferation in endometrial cancer cells, while metformin reverses this effect and inhibits cell proliferation. However, the effects of metformin on the regulation of the IGF signaling pathway are unclear. The aim of this study was to investigate the regulation of IGF signaling by metformin in endometrial cancer cells, and to determine the effects of metformin combined with IGF-1 receptor (IGF-1R) inhibitor on cell proliferation and apoptosis. Cell proliferation was assessed following exposure of Ishikawa and HEC-1B endometrial cancer cell lines to metformin and/or the IGF-1R inhibitor, PPP. Apoptosis was assessed by TdT-mediated dUTP nick end labeling assay. Metformin was observed to downregulate IGF-1R and upregulate IGF binding protein-1 (IGFBP-1) mRNA and protein expression, while compound C, an adenosine monophosphate protein kinase inhibitor, reversed this effect. Metformin administered with PPP inhibited endometrial cancer cell proliferation to a greater degree than treatment with either agent alone. At high concentrations (1 or 2 mM), metformin induced apoptosis in endometrial cancer cells. Metformin combined with IGF-1R axis inhibitors may act synergistically to kill tumor cells, as metformin was shown to delay and prevent IGF-1R feedback. In conclusion, this study supported the results of animal studies and subclinical studies, demonstrating the feasibility of metformin combined with IGF-1R axis inhibitors in the treatment of endometrial cancer. PMID:25289085

  3. Selective CB2 up-regulation in women affected by endometrial inflammation

    PubMed Central

    Iuvone, Teresa; De Filippis, Daniele; Di Spiezio Sardo, Attilio; D'Amico, Alessandra; Simonetti, Sara; Sparice, Stefania; Esposito, Giuseppe; Bifulco, Giuseppe; Insabato, Luigi; Nappi, Carmine; Guida, Maurizio

    2008-01-01

    Abstract Endometritis is defined as an inflammation of the endometrial mucosa of the uterus. In endometritis large amounts of toxic mediators, including nitric oxide (NO) are released by inflammatory cells. As a consequence of nitric oxide-dependent injury, the cells respond by triggering protective mechanisms, by changing the endo-cannabinoid system (ECS) which comprises both CB1 and CB2 cannabinoid receptors and their endogenous ligands. The aim of our study was to seek out evidence for the presence of cannabinoid receptors in inflammatory endometrial tissue as well as for their potential role in endometrial inflammation. Our results showed a selective up-regulation of both transcription and expression of CB2 receptors in biopsies from women affected by endometrial inflammation compared to healthy women. The experiments with the nitric oxide-donor S-Nitroso-L-Glutathione (GSNO) suggest that such a selective up-regulation may be related to the nitric oxide release occurring during endometrial inflammation. In addition, we demonstrated an increase in chymase expression, a marker of mast cells, in biopsies of women affected by endometritis. Therefore our results support the hypothesis that the up-regulation of CB2 occurs mainly on mast cells and that it might tend to sensitize these cells to the anti-inflammatory effect exerted by endogenous cannabinoids by binding their receptor and thus preventing the mast cell degranulation and the release of pro-inflammatory mediators. In conclusion, we believe that the selective CB2 up-regulation might play a role as a novel prognostic factor in endometrial inflammation. PMID:18419603

  4. Endometrial ablation

    MedlinePlus

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

  5. Akt regulates Progesterone Receptor B dependent transcription and angiogenesis in endometrial cancer cells

    PubMed Central

    Lee, Irene I.; Maniar, Kruti; Lydon, John P.; Kim, J. Julie

    2016-01-01

    Progestins have long been used clinically for the treatment of endometrial cancers, however, the response rates to progestin therapy vary and the molecular mechanisms behind progestin insensitivity are poorly understood. We hypothesized that in PTEN mutated endometrial cancers, hyperactive Akt signaling downregulates Progesterone Receptor B (PRB) transcriptional activity, leading to overall impaired progestin responses. We report that inhibition of Akt with the Akt inhibitor, MK-2206 (MK), in conjunction with progestin (R5020) treatment, is sufficient to upregulate a subset of PRB target genes in Ishikawa cells stably expressing PRB (PRB-Ishikawa). Through gene ontology analysis of Akt-regulated PRB target genes, angiogenesis was found to be the principle process regulated by Akt-PRB. To further interrogate the mechanism by which Akt modulates PRB transcriptional activity, ChIP-Mass Spectrometry was performed to identify potential cofactors that differentially interact with PRB in the presence of the R5020 and MK+R5020. 14-3-3σ was identified as a protein enriched in the MK+R5020 dataset, and it was demonstrated that 14-3-3σ is required for the upregulation in PRB target gene expression following inhibition of Akt. In order to determine the ramifications of MK+R5020 treatment on angiogenesis, in vitro assays were performed and combinatorial MK+R5020 treatment significantly decreased endothelial cell invasion and tube formation more than MK or R5020 treatment alone. Furthermore, we found that combinatorial MK-2206+Progesterone treatments decreased angiogenesis and proliferation in the Ptend/d conditional mouse model of endometrial cancer. Taken together, these findings suggest that a combinatorial therapeutic approach utilizing Akt inhibitors with progestins may improve the efficacy of progestin therapy for the treatment of endometrial cancer. PMID:26996671

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

    PubMed Central

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

    2011-01-01

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

  7. MiR-183 Regulates ITGB1P Expression and Promotes Invasion of Endometrial Stromal Cells

    PubMed Central

    Chen, Jie; Gu, Lin; Ni, Jie; Hu, Ping; Hu, Kai; Shi, Ying-Li

    2015-01-01

    We applied in the previous study miRNA microarray screening analysis to identify several differentially expressed miRNAs, including miR-183 in normal, eutopic, and ectopic endometrium. Knockdown of miR-183 expression induced the invasiveness and inhibition of apoptosis in endometrial stromal cells. The current study aims to identify the miR-183 targets with relevance to cell functions in endometrial stromal cells, to verify the interaction of miR-183 with its target genes, and to confirm the role of miR-183 in the process of endometriosis. Using microarray analysis, we identified 27 differentially expressed genes (19 were upregulated and 8 downregulated), from which we selected 4 downregulated genes (ITGB1, AMIGO2, VAV3, and PSEN2) based on GO databases for functional analysis and significant pathway analysis. Western blotting analyses showed that integrin β1 (ITGB1), but not AMIGO2, was affected by miR-183 overexpression, whereas no protein expression of VAV3 and PSEN2 was detected. Luciferase reporter assay verified that ITGB1 is a target gene of miR-183. Moreover, we found that ITGB1 is overexpressed in the endometrium of endometriosis patients. Furthermore, overexpression of ITGB1 rescued the repressive effects of miR-183 on the invasiveness of endometrial stromal cells. These findings, together with the fact that ITGB1 is a critical factor for cell adhesion and invasiveness, suggest that miR-183 may be involved in the development of endometriosis by regulating ITGB1 in endometrial stromal cells. PMID:26357653

  8. KSR1 Is Overexpressed in Endometrial Carcinoma and Regulates Proliferation and TRAIL-Induced Apoptosis by Modulating FLIP Levels

    PubMed Central

    Llobet, David; Eritja, Nuria; Domingo, Monica; Bergada, Laura; Mirantes, Cristina; Santacana, Maria; Pallares, Judit; Macià, Anna; Yeramian, Andree; Encinas, Mario; Moreno-Bueno, Gema; Palacios, Jose; Lewis, Robert E.; Matias-Guiu, Xavier; Dolcet, Xavi

    2011-01-01

    The Raf/MEK/extracellular signal-regulated kinase (ERK) pathway participates in many processes altered in development and progression of cancer in human beings such as proliferation, transformation, differentiation, and apoptosis. Kinase suppressor of Ras 1 (KSR1) can interact with various kinases of the Raf/MEK/extracellular signal-regulated kinase pathway to enhance its activation. The role of KSR1 in endometrial carcinogenesis was investigated. cDNA and tissue microarrays demonstrated that expression of KSR1 was up-regulated in endometrial carcinoma. Furthermore, inhibition of KSR1 expression by specific small hairpin RNA resulted in reduction of both proliferation and anchorage-independent cell growth properties of endometrial cancer cells. Because inhibition of apoptosis has a pivotal role in endometrial carcinogenesis, the effects of KSR1 in regulation of tumor necrosis factor–related apoptosis-inducing ligand (TRAIL)–induced apoptosis were investigated. KSR1 knock-down sensitized resistant endometrial cell lines to both TRAIL- and Fas-induced apoptosis. Sensitization to TRAIL and agonistic anti-Fas antibody was caused by down-regulation of FLIP (FLICE-inhibitory protein). Also investigated was the molecular mechanism by which KSR1 regulates FLIP protein levels. It was demonstrated that KSR1 small hairpin RNA did not affect FLIP transcription or degradation. Rather, FLIP down-regulation was caused by Fas-associated death domain protein–dependent inhibition of FLIP translation triggered after TRAIL stimulation in KSR1-silenced cells. Re-expression of heterologous KSR1 in cells with down-regulated endogenous KSR1 restored FLIP protein levels and TRAIL resistance. In conclusion, KSR1 regulates endometrial sensitivity to TRAIL by regulating FLIP levels. PMID:21435442

  9. Estradiol regulates MICA expression in human endometrial cells

    PubMed Central

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

    2008-01-01

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

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

    PubMed

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

    2016-07-15

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

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

    PubMed

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

    2008-01-01

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

  12. Proteomic analysis identifies interleukin 11 regulated plasma membrane proteins in human endometrial epithelial cells in vitro

    PubMed Central

    2011-01-01

    Background During the peri-implantation period, the embryo adheres to an adequately prepared or receptive endometrial surface epithelium. Abnormal embryo adhesion to the endometrium results in embryo implantation failure and infertility. Endometrial epithelial cell plasma membrane proteins critical in regulating adhesion may potentially be infertility biomarkers or targets for treating infertility. Interleukin (IL) 11 regulates human endometrial epithelial cells (hEEC) adhesion. Its production is abnormal in women with infertility. The objective of the study was to identify IL11 regulated plasma membrane proteins in hEEC in vitro using a proteomic approach. Methods Using a 2D-differential in-gel electrophoresis (DIGE) electrophoresis combined with LCMS/MS mass spectrometry approach, we identified 20 unique plasma membrane proteins differentially regulated by IL11 in ECC-1 cells, a hEEC derived cell line. Two IL11 regulated proteins with known roles in cell adhesion, annexin A2 (ANXA2) and flotillin-1 (FLOT1), were validated by Western blot and immunocytochemistry in hEEC lines (ECC-1 and an additional cell line, Ishikawa) and primary hEEC. Flotilin-1 was further validated by immunohistochemistry in human endometrium throughout the menstrual cycle (n = 6-8/cycle). Results 2D-DIGE analysis identified 4 spots that were significantly different between control and IL11 treated group. Of these 4 spots, there were 20 proteins that were identified with LCMS/MS. Two proteins; ANXA2 and FLOT1 were chosen for further analyses and have found to be significantly up-regulated following IL11 treatment. Western blot analysis showed a 2-fold and a 2.5-fold increase of ANXA2 in hEEC membrane fraction of ECC-1 and Ishikawa cells respectively. Similarly, a 1.8-fold and a 2.3/2.4-fold increase was also observed for FLOT1 in hEEC membrane fraction of ECC-1 and Ishikawa cells respectively. In vitro, IL11 induced stronger ANXA2 expression on cell surface of primary hEEC and ECC-1 whilst

  13. 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.

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

    PubMed Central

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

    2014-01-01

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

  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. 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.

  17. Metformin down-regulates endometrial carcinoma cell secretion of IGF-1 and expression of IGF-1R.

    PubMed

    Zhang, Yu; Li, Meng-Xiong; Wang, Huan; Zeng, Zheng; Li, Xiao-Mao

    2015-01-01

    As metformin can inhibit endometrial carcinoma (EC) cell growth and the insulin growth factor (IGF) system is active in EC, the question of whether t can regulate endometrial carcinoma cell secretion of IGF-1 or expression of IGF-1 receptor (IGF-1R) is of interest. In this study, serum IGF-1 levels in EC patients were found to be comparable with that in the non EC patients (p>0.05). However, the IGF-1 level in the medium of cultured cells after treatment with metformin was decreased (p<0.05). IGF-1R was highly expressed in human endometrial carcinoma paraffin sections, but IGF-1R and phosphor-protein kinase B/protein kinase B (p-Akt/ Akt) expression was down-regulated after metformin treatment (p<0.05). In summary, metformin can reduce the secretion of IGF-1 by Ishikawa and JEC EC cell lines and their expression of IGF-1R to deactivate downstream signaling involving the PI-3K/Akt pathway to inhibit endometrial carcinoma cell growth.

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

    PubMed

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

    2016-01-01

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

  19. Endometrial polyps

    MedlinePlus

    Uterine polyps ... one knows exactly why some women get endometrial polyps. They tend to grow when there is more ... the hormone estrogen in the body. Most endometrial polyps are not cancerous. About 5% can be cancerous ...

  20. [Endometrial imaging].

    PubMed

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

    2000-12-01

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

  1. Notch1 Is Regulated by Chorionic Gonadotropin and Progesterone in Endometrial Stromal Cells and Modulates Decidualization in Primates

    PubMed Central

    Afshar, Yalda; Miele, Lucio

    2012-01-01

    No other tissue in the body undergoes such a vast and extensive growth and remodeling in a relatively short period of time as the primate endometrium. Endometrial integrity is coordinated by ovarian hormones, namely, estrogens, progesterone, and the embryonic hormone chorionic gonadotropin (CG). These regulated events modulate the menstrual cycle and decidualization. The Notch family of transmembrane receptors regulate cellular proliferation, differentiation, and apoptosis, cellular processes required to maintain endometrial integrity. In two primate models, the human and the simulated pregnant baboon model, we demonstrated that Notch1 is increased during the window of uterine receptivity, concomitant with CG. Furthermore, CG combined with estrogens and progesterone up-regulate the level of Notch1, whereas progesterone increases the intracellular transcriptionally competent Notch1, which binds in a complex with progesterone receptor. Inhibition of Notch1 prevented decidualization, and alternatively, when decidualization is biochemically recapitulated in vitro, Notch1 is down-regulated. A focused microarray demonstrated that the Notch inhibitor, Numb, dramatically increased when Notch1 decreased during decidualization. We propose that in the endometrium, Notch has a dual role during the window of uterine receptivity. Initially, Notch1 mediates a survival signal in the uterine endometrium in response to CG from the implanting blastocyst and progesterone, so that menstrual sloughing is averted. Subsequently, Notch1 down-regulation may be critical for the transition of stromal fibroblast to decidual cells, which is essential for the establishment of a successful pregnancy. PMID:22535768

  2. Gene transcription of TLR2, TLR4, LPS ligands and prostaglandin synthesis enzymes are up-regulated in canine uteri with cystic endometrial hyperplasia-pyometra complex.

    PubMed

    Silva, E; Leitão, S; Henriques, S; Kowalewski, M P; Hoffmann, B; Ferreira-Dias, G; da Costa, L Lopes; Mateus, L

    2010-01-01

    Escherichia coli (E. coli) is the most frequent bacterium isolated in cases of cystic endometrial hyperplasia-pyometra complex, the most frequent endometrial disorder in the bitch. Toll-like receptors (TLRs) play an essential role in the innate immune system. The aim of this study was to compare transcription of genes encoding TLR2, TLR4 and LPS ligands (CD14, MD-2, LBP), prostaglandin synthesis enzymes (COX1, COX2, PGES1 and PGFS), and to compare COX1 and COX2 protein expression and PGE(2) and PGF(2alpha) endometrial content in the endometrium of canine diestrous uteri with (n=7) or without (n=7) pyometra. All cases of pyometra were hyperplastic and E. coli was the only isolated bacteria, while diestrous normal uteri did not present signs of cystic endometrial hyperplasia and were negative for bacteriology. Except for COX1, transcription of all genes was significantly higher in pyometra than in normal endometria. COX1 protein was observed in both normal and pyometra uteri, but COX2 protein was only present in pyometra cases. Endometrial PGE(2) and PGF(2alpha) content were significantly higher in pyometra than in normal diestrous endometria. In conclusion, data obtained in this study provides evidence that pyometra-isolated E. coli induces the up-regulation of TLR2 and TLR4 genes in the canine diestrous endometrium. This up-regulation, which is probably the result of the stimulation by LPS and lipoprotein E. coli constituents, leads to the endometrial up-regulation of PG synthesis genes. This, in turn, results in a higher endometrial concentration of PGE(2) and PGF(2alpha), which may further regulate the local inflammatory response. PMID:19945173

  3. Hormones and endometrial carcinogenesis.

    PubMed

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

    2016-02-01

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

  4. Prostaglandin F2α-F-prostanoid receptor regulates CXCL8 expression in endometrial adenocarcinoma cells via the calcium–calcineurin–NFAT pathway

    PubMed Central

    Sales, Kurt J.; Maldonado-Pérez, David; Grant, Vivien; Catalano, Rob D.; Wilson, Martin R.; Brown, Pamela; Williams, Alistair R.W.; Anderson, Richard A.; Thompson, E. Aubrey; Jabbour, Henry N.

    2009-01-01

    Pro-inflammatory mediators, like prostaglandin (PG) and chemokines, promote tumourigenesis by enhancing cell proliferation, migration of immune cells and recruitment of blood vessels. Recently we showed elevated expression of the chemokine (C-X-C motif) receptor 2 (CXCR2) in endometrial adenocarcinomas localized to neutrophils and neoplastic epithelial and vascular cells. Furthermore we found that PGF2α-F-prostanoid (FP) receptor regulates the expression of the CXCR2 ligand CXCL1, to promote neutrophil chemotaxis in endometrial adenocarcinomas. In the present study we identified another CXCR2 ligand, CXCL8 as a target for PGF2α-FP receptor signalling which enhances epithelial cell proliferation in endometrial adenocarcinoma cells in vitro and in nude mice in vivo. We found that PGF2α-FP receptor interaction induces CXCL8 expression in endometrial adenocarcinoma cells via the protein kinase C–calcium–calcineurin–NFAT signaling pathway. Promoter analysis revealed that CXCL8 transcriptional activation by PGF2α signaling is mediated by cooperative interactions between the AP1 and NFAT binding sites. Furthermore, PGF2α via the FP receptor induced the expression of the regulator of calcineurin 1 isoform 4 (RCAN1-4) via the calcineurin/NFAT pathway in a reciprocal manner to CXCL8. Using an adenovirus to overexpress RCAN1-4, we found that RCAN1-4 is a negative regulator of CXCL8 expression in endometrial adenocarcinoma cells. Taken together our data have elucidated the molecular and cellular mechanism whereby PGF2α regulates CXCL8 expression via the FP receptor in endometrial adenocarcinomas and have highlighted RCAN1-4 as a negative regulator of CXCL8 expression which may be exploited therapeutically to inhibit CXCL8-mediated tumour development. PMID:19819266

  5. 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

  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. 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 • ...

  9. 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? ...

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

    PubMed Central

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

    2016-01-01

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

  11. 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

  12. 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

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

    PubMed

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

    2015-04-01

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

  14. MicroRNAs miR-30b, miR-30d, and miR-494 Regulate Human Endometrial Receptivity

    PubMed Central

    Martinez-Conejero, Jose A.; Esteban, Francisco J.; Ruiz-Alonso, Maria; Stavreus-Evers, Anneli; Horcajadas, Jose A.; Salumets, Andres

    2013-01-01

    MicroRNAs (miRNAs) act as important epigenetic posttranscriptional regulators of gene expression. We aimed to gain more understanding of the complex gene expression regulation of endometrial receptivity by analyzing miRNA signatures of fertile human endometria. We set up to analyze miRNA signatures of receptive (LH + 7, n = 4) versus prereceptive (LH + 2, n = 5) endometrium from healthy fertile women. We found hsa-miR-30b and hsa-miR-30d to be significantly upregulated, and hsa-miR-494 and hsa-miR-923 to be downregulated in receptive endometrium. Three algorithms (miRanda, PicTar, and TargetScan) were used for target gene prediction. Functional analyses of the targets using Ingenuity Pathways Analysis and The Database for Annotation, Visualization and Integrated Discovery indicated roles in transcription, cell proliferation and apoptosis, and significant involvement in several relevant pathways, such as axon guidance, Wnt/β-catenin, ERK/MAPK, transforming growth factor β (TGF-β), p53 and leukocyte extravasation. Comparison of predicted miRNA target genes and our previous messenger RNA microarray data resulted in a list of 12 genes, including CAST, CFTR, FGFR2, and LIF that could serve as a panel of genes important for endometrial receptivity. In conclusion, we suggest that a subset of miRNAs and their target genes may play important roles in endometrial receptivity. PMID:22902743

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

    ERIC Educational Resources Information Center

    Holland, Rochelle

    2006-01-01

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

  16. 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

  17. 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.

  18. 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.

  19. Transcription factor Egr1 acts as an upstream regulator of beta-catenin signalling through up-regulation of TCF4 and p300 expression during trans-differentiation of endometrial carcinoma cells.

    PubMed

    Saegusa, M; Hashimura, M; Kuwata, T; Hamano, M; Watanabe, J; Kawaguchi, M; Okayasu, I

    2008-12-01

    The beta-catenin/TCF4/p300 pathway is involved in early signalling for trans-differentiation towards the morular phenotype of endometrial carcinoma cells, but little is known about the upstream regulators. Here we show that transcription factor early growth response 1 (Egr1) acts as an initial mediator through up-regulating the expression of TCF4 and p300. In an endometrial carcinoma cell line with abundant oestrogen receptor alpha, Egr1 expression at both mRNA and protein levels was significantly increased by serum and 17beta-oestradiol stimuli. Serum-stimulated cells also showed increased expression of TCF4 and p300, while inhibition of Egr1 by specific siRNAs resulted in decreased expression. Transfection of Egr1 led to transactivation of TCF4 as well as p300 genes, through specific binding to a promoter region, and thus in turn resulted in nuclear accumulation of beta-catenin mediated by the up-regulating TCF4. The overexpression also caused inhibition of beta-catenin/TCF4/p300-mediated transcription, probably through sequestration of p300. Egr1 promoter activity was increased by serum but not 17beta-oestradiol, in contrast to the marked repression associated with TCF4, p300, and Egr1 itself, indicating that the regulation involves several feedback loops. In clinical samples, cells immunopositive for nuclear Egr1, as well as beta-catenin and TCF4, were found to be sporadically distributed in glandular components of endometrial carcinoma with morules. A significant positive correlation between nuclear beta-catenin and TCF4 was observed, but no such link was evident for Egr1, probably due to the existence of negative feedback regulation. Together, these data indicate that Egr1 may participate in modulation of the beta-catenin/TCF4/p300 signalling pathway as an initial event during trans-differentiation of endometrial carcinoma cells, through its impact on several signalling networks.

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

    PubMed Central

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

    2016-01-01

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

  1. From endometrial receptivity to infertility.

    PubMed

    Tabibzadeh, S; Shea, W; Lessey, B A; Broome, J

    1999-01-01

    Implantation of the blastocyst in endometrium requires establishment of a coordinated molecular dialogue between the embryo and the endometrium. Factors instrumental in the preparation of a receptive endometrium are derived from the hypothalamic-pituitary-gonadal axis. These factors modulate the expression of genes that drive the endometrium throughout the characteristic menstrual cycles. During each menstrual cycle, a series of coordinated, architectural, morphological, cytochemical, and molecular changes ultimately lead to the preparation of a receptive endometrium during the putative "receptive period" or "implantation window." It is during this critical period that a proper dialogue can be established between an intrusive blastocyst and a receptive endometrium. If, for any reason, this dialogue is not established or is perturbed, the embryo is aborted. The natural fate of the receptive endometrium, in the absence of implantation, is development of a second set of changes that ultimately lead to menstruation. The identity of the molecular repertoire that makes endometrium receptive to implantation and/or lead to menstruation is being revealed and broadly includes cytokines, heat shock factors, adhesion molecules and matrix metalloproteases. We identified a novel gene of the transforming growth factor-beta, superfamily of molecules, the so-called endometrial bleeding--associated factor or ebaf, whose expression is confined to the late secretory and menstrual phases. Various forms of female infertility were associated with dysregulated expression of ebaf during the implantation window. The findings show an occult molecular defect of endometrial receptivity that seems to be due to dysregulated and premature expression of a member of the premenstrual molecular repertoire. The dysregulated expression of ebaf may assist in the identification, prognostication, and monitoring of treatment of infertile women.

  2. Curcumin suppresses constitutive activation of STAT-3 by up-regulating protein inhibitor of activated STAT-3 (PIAS-3) in ovarian and endometrial cancer cells.

    PubMed

    Saydmohammed, Manush; Joseph, Doina; Syed, Viqar

    2010-05-15

    Signal transducer and activator of transcription-3 (STAT-3) is constitutively activated in ovarian and endometrial cancers and is implicated in uncontrolled cell growth. Thus, its disruption could be an effective approach to control tumorigenesis. Curcumin is a dihydroxyphenolic compound, with proven anti-cancer efficacy in various cancer models. We examined the anti-tumor mechanism of curcumin on STAT-3 and on the negative regulators of STAT-3, including suppressors of cytokine signaling proteins (SOCS-1 and SOCS-3), protein inhibitors of activated STAT (PIAS-1 and PIAS-3), and SH2 domain-containing phosphatases (SHP-1 and SHP-2) in ovarian and endometrial cancer cell lines. Treatment of cancer cells with curcumin induced a dose- and time-dependent decrease of constitutive IL-6 expression and of constitutive and IL-6-induced STAT-3 phosphorylation, which is associated with decreased cell viability and increased cleavage of caspase-3. The inhibition of STAT-3 activation by curcumin was reversible, and phosphorylated STAT-3 levels returned to control levels 24 h after curcumin removal. Compared to normal cells baseline expression of SOCS-3 was high in cancer cells and a marked decrease in SOCS-3 expression was seen following curcumin treatment. Overexpression of SOCS-3 in curcumin-treated cells increased expression of phosphorylated STAT-3 and resulted in increased cell viability. Normal ovarian and endometrial cells exhibited high expression of PIAS-3 protein, whereas in cancer cells the expression was greatly reduced. Curcumin increased PIAS-3 expression in cancer cells. Of significance, siRNA-mediated knockdown of PIAS-3 overcomes the inhibitory effect of curcumin on STAT-3 phosphorylation and cell viability. In conclusion, curcumin suppresses JAK-STAT signaling via activation of PIAS-3, thus attenuating STAT-3 phosphorylation and tumor cell growth.

  3. What Is Endometrial Cancer?

    MedlinePlus

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

  4. 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

  5. Oxytocin Increases Invasive Properties of Endometrial Cancer Cells Through Phosphatidylinositol 3-Kinase/AKT-Dependent Up-Regulation of Cyclooxygenase-1, -2, and X-Linked Inhibitor of Apoptosis Protein1

    PubMed Central

    Déry, Marie-Claude; Chaudhry, Parvesh; Leblanc, Valérie; Parent, Sophie; Fortier, Anne-Marie; Asselin, Eric

    2011-01-01

    Traditionally, oxytocin (OT) is well known to play a crucial role in the regulation of cyclic changes in the uterus, implantation of the embryo, and parturition. Recently, an additional role for OT has been identified in several types of cancer cells in which OT acts as a growth regulator. In endometrial cancer cells, OT is known to efficiently inhibit cellular proliferation. In the present study, we show that OT increases invasiveness of human endometrial carcinoma (HEC) cells, which are otherwise resistant to the growth-inhibiting effects of OT. Using pharmacological inhibitors, invasion assay, RNA interference, and immunofluorescence, we found that OT enhances the invasive properties of HEC cells through up-regulation of X-linked inhibitor of apoptosis protein (XIAP), matrix-metalloproteinase 2 (MMP2), and matrix-metalloproteinase 14 (MMP14). In addition, we show that OT-mediated invasion is both cyclooxygenase 1 (PTGS1) and cyclooxygenase-2 (PTGS2) dependent via the phosphatidylinositol 3-kinase/AKT (PIK3/AKT) pathway. PTGS2 knockdown by shRNA resulted in XIAP down-regulation. We also show that OT receptor is overexpressed in grade I to III endometrial cancer. Taken together, our results describe for the first time a novel role for OT in endometrial cancer cell invasion. PMID:21816851

  6. Endometrial haemostasis and menstruation.

    PubMed

    Davies, Joanna; Kadir, Rezan A

    2012-12-01

    Under normal physiological circumstances menstruation is a highly regulated, complex process that is under strict hormonal control. During normal menstruation, progesterone withdrawal initiates menstruation. The cessation of menstrual bleeding is achieved by endometrial haemostasis via platelet aggregation, fibrin deposition and thrombus formation. Local endocrine, immunological and haemostatic factors interact at a molecular level to control endometrial haemostasis. Tissue factor and thrombin play a key role locally in the cessation of menstrual bleeding through instigation of the coagulation factors. On the other hand, fibrinolysis prevents clot organisation within the uterine cavity while plasminogen activator inhibitors (PAI) and thrombin-activatable fibrinolysis inhibitors control plasminogen activators and plasmin activity. Abnormalities of uterine bleeding can result from imbalance of the haemostatic factors. The most common abnormality of uterine bleeding is heavy menstrual bleeding (HMB). Modern research has shown that an undiagnosed bleeding disorder, in particular von Willebrand disease (VWD) and platelet function disorders, can be an underlying cause of HMB. This has led to a change in the approach to the management of HMB. While full haemostatic assessment is not required for all women presenting with HMB, menstrual score and bleeding score can help to discriminate women who are more likely to have a bleeding disorder and benefit from laboratory haemostatic evaluation. Haemostatic agents (tranexamic acid and DDAVP) enhance systemic and endometrial haemostasis and are effective in reducing menstrual blood loss in women with or without bleeding disorders. Further research is required to enhance our understanding of the complex interactions of haemostatic factors in general, and specifically within the endometrium. This will lead to the development of more targeted interventions for the management of abnormal uterine bleeding in the future.

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

    ClinicalTrials.gov

    2016-10-25

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

  8. 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,…

  9. 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

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

    ClinicalTrials.gov

    2016-08-24

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

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

    PubMed

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

    2014-10-01

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

  12. 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

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

    PubMed

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

    2015-10-13

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

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

    PubMed Central

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

    2016-01-01

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

  15. Endometrial pneumatosis (emphysematous endometritis).

    PubMed

    Chua, Yee Jia; Meharry, Suzanne; Harding, Steven; Stewart, Colin J R

    2014-09-01

    Endometrial pneumatosis, also referred to as pneumopolycystic or emphysematous endometritis, is a rare condition reported only twice previously in the literature and only once as an isolated finding. We report a case of endometrial pneumatosis in a 43-yr-old patient who underwent hysterectomy and bilateral salpingectomy for treatment of a symptomatic uterine leiomyoma. No predisposing factors towards pneumatosis were identified and in particular there was no evidence of immune impairment, diabetes mellitus, uterine infection, or prior surgical intervention. Endometrial pneumatosis remains an enigmatic condition of uncertain etiology but it appears to be self-limited with no known pathologic sequelae. PMID:25083968

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

    PubMed

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

    2015-09-01

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

  17. Endometrial Cancer Risk Factors

    MedlinePlus

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

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

    PubMed

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

    2012-03-01

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

  19. NAC1, a potential stem cell pluripotency factor expression in normal endometrium, endometrial hyperplasia and endometrial carcinoma.

    PubMed

    Ishikawa, Masako; Nakayama, Kentaro; Yeasmin, Shamima; Katagiri, Atsuko; Iida, Kouji; Nakayama, Naomi; Miyazaki, Kohji

    2010-05-01

    The purpose of this study was to investigate the role of NAC1 in the development of endometrial cancer. NAC1 expression and localization were assessed with immunohistochemistry in the normal cyclic human endometrium, hyperplastic endometrium, and endometrial cancer. Expression of NAC1 in the glandular cells was significantly higher in the early and mid proliferative phases than in the other menstrual phases, endometrial hyperplasia, and endometrial carcinoma. NAC1 expression was down-regulated during endometrial carcinogenesis. There were significant correlations between positive NAC1 expression and pathological grade (P=0.037). No significant associations were found between NAC1 expression and the other clinicopathological characteristics including patient age, FIGO staging, depth of myometrial invasion, pelvic lymph node metastasis, lymphovascular space invasion, menopause, or body mass index. NAC1 gene knockdown inhibited cell growth and induced apoptosis in Ishikawa, HHUA, and JHEM2 cell lines, all of which overexpressed NAC1. Ectopic overexpression of the NAC1 gene stimulated cell proliferation in the HEC1B, and JHEM1 endometrial cancer cell lines, which have lower endogenous NAC1 expression. Endometrial carcinomas with NAC1 overexpression are clinically aggressive, high-grade carcinomas. Therefore, detection of NAC1 overexpression in endometrial cancers may identify patients who will benefit from NAC1 targeted therapy.

  20. General Information About Endometrial Cancer

    MedlinePlus

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

  1. 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

  2. Insulin-like growth factor 1 regulates growth of endometrial carcinoma through PI3k signaling pathway in insulin-resistant type 2 diabetes

    PubMed Central

    Dai, Congwei; Li, Na; Song, Guangyao; Yang, Yanyan; Ning, Xiaoran

    2016-01-01

    Previous studies have shown that insulin-like growth factor 1 (IGF-1) may be responsible for the higher risk for developing endometrial carcinoma (EMC) in insulin-resistant type 2 diabetes mellitus (T2DM) patients. However, the underlying mechanisms are not understood. Here, we compared T2DM patients with or without EMC. We did not find difference in the serum levels of IGF-1, insulin-like growth factor 2 (IGF-2), IGF-1 binding protein 3, as well as the activation of IGF-1 receptor (IGF1R) in endometrial cells between T2DM patients with or without EMC. However, the levels of IGF2R activation and activation of PI3k, an IGF1R downstream factor, were significantly higher in endometrial cells in T2DM patients with EMC. In vitro analyses of activation of IGF1R, IGF2R, PI3k and CCND1 in EMC cells or IGF2R-overexpressing EMC cells by IGF-1 or IGF-2 suggest that increases in IGF2R in endometrial cells in T2DM may increase PI3k/CCND1-dependent cell growth through loss of competitive binding of IGF-2 to IGF1R, as a possible explanation for the higher risk for developing EMC in T2DM.

  3. Insulin-like growth factor 1 regulates growth of endometrial carcinoma through PI3k signaling pathway in insulin-resistant type 2 diabetes

    PubMed Central

    Dai, Congwei; Li, Na; Song, Guangyao; Yang, Yanyan; Ning, Xiaoran

    2016-01-01

    Previous studies have shown that insulin-like growth factor 1 (IGF-1) may be responsible for the higher risk for developing endometrial carcinoma (EMC) in insulin-resistant type 2 diabetes mellitus (T2DM) patients. However, the underlying mechanisms are not understood. Here, we compared T2DM patients with or without EMC. We did not find difference in the serum levels of IGF-1, insulin-like growth factor 2 (IGF-2), IGF-1 binding protein 3, as well as the activation of IGF-1 receptor (IGF1R) in endometrial cells between T2DM patients with or without EMC. However, the levels of IGF2R activation and activation of PI3k, an IGF1R downstream factor, were significantly higher in endometrial cells in T2DM patients with EMC. In vitro analyses of activation of IGF1R, IGF2R, PI3k and CCND1 in EMC cells or IGF2R-overexpressing EMC cells by IGF-1 or IGF-2 suggest that increases in IGF2R in endometrial cells in T2DM may increase PI3k/CCND1-dependent cell growth through loss of competitive binding of IGF-2 to IGF1R, as a possible explanation for the higher risk for developing EMC in T2DM. PMID:27648123

  4. DNA Methylation Machinery in the Endometrium and Endometrial Cancer.

    PubMed

    Caplakova, Veronika; Babusikova, Eva; Blahovcova, Eva; Balharek, Tomas; Zelieskova, Maria; Hatok, Jozef

    2016-09-01

    During the normal menstrual cycle, endometrial tissue undergoes many biochemical and morphological changes which are under the control of steroid hormone levels. DNA methylation plays a key role in gene expression regulation and influences functional changes in endometrial tissue. Eliminating senescent cells from the functional layer of the endometrium is mediated by apoptotic cell death, which helps maintain cellular homeostasis. Aberrant DNA methylation changes result in deregulation of important apoptotic proteins during endometrial carcinogenesis and thus apoptosis resistance development. Evading apoptosis is still a major problem in the successful treatment of endometrial cancer patients with advanced disease. Despite intensive study of the cancer epigenome, there is missing information about disrupted apoptotic gene regulation in DNA methylation levels. Therefore, it is necessary to spread our knowledge in the field of epigenetics to help us differentiate normal and cancer tissues and detect the early stages of cancer disease. PMID:27630276

  5. Evaluation of the anti-tumor effects of lactate dehydrogenase inhibitor galloflavin in endometrial cancer cells.

    PubMed

    Han, Xiaoyun; Sheng, Xiugui; Jones, Hannah M; Jackson, Amanda L; Kilgore, Joshua; Stine, Jessica E; Schointuch, Monica N; Zhou, Chunxiao; Bae-Jump, Victoria L

    2015-01-29

    High rates of aerobic glycolysis represent a key mechanism by which endometrial cancer cells consume glucose as its primary energy source. The up-regulated glycolytic pathway is a common therapeutic target whose inhibition has implications for anti-tumor activity in cancer cells. The present study was aimed at evaluating the potential of a novel lactate dehydrogenase (LDH) inhibitor, Galloflavin, as a therapeutic agent for endometrial cancer. Our results revealed that Galloflavin effectively inhibited cell growth in endometrial cancer cell lines and primary cultures of human endometrial cancer through its involvement in multiple signaling pathways that regulate metabolism, cell cycle, apoptosis, cell stress and metastasis.

  6. RNF43 is frequently mutated in colorectal and endometrial cancers

    PubMed Central

    Giannakis, Marios; Hodis, Eran; Mu, Xinmeng Jasmine; Yamauchi, Mai; Rosenbluh, Joseph; Cibulskis, Kristian; Saksena, Gordon; Lawrence, Michael S.; Qian, ZhiRong; Nishihara, Reiko; Van Allen, Eliezer M.; Hahn, William C.; Gabriel, Stacey B.; Lander, Eric S.; Getz, Gad; Ogino, Shuji; Fuchs, Charles S.; Garraway, Levi A.

    2014-01-01

    We report somatic mutations of RNF43 in over 18% of colorectal adenocarcinomas and endometrial carcinomas. RNF43 encodes an E3 ubiquitin ligase that negatively regulates Wnt signaling. Truncating mutations of RNF43 are more prevalent in microsatellite-unstable tumors and show mutual exclusivity with inactivating APC mutations in colorectal adenocarcinomas. These results indicate that RNF43 is one of the most commonly mutated genes in colorectal and endometrial cancers. PMID:25344691

  7. Cancer Statistics: Endometrial Cancer

    MedlinePlus

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

  8. Bisphenol A-induced epithelial to mesenchymal transition is mediated by cyclooxygenase-2 up-regulation in human endometrial carcinoma cells.

    PubMed

    Wang, Kai-Hung; Kao, An-Pei; Chang, Chia-Cheng; Lin, Ta-Chin; Kuo, Tsung-Cheng

    2015-12-01

    Many studies have highlighted the correlation between the increase of bisphenol A (BPA) level in the environment and the incidence of tumor in humans. In human carcinogenesis, the overexpression of cyclooxygenase-2 (COX-2) and epithelial-mesenchymal transition (EMT) are closely related with tumor development. In this study, human endometrial carcinoma cells line (RL95-2) was used to investigate whether BPA can induce EMT and COX-2 expression. The results show that BPA increased growth rate and colony-forming efficiency in a dose-dependent manner, induced EMT and COX-2 gene expression and promoted the migration and invasion ability of RL95-2 cells. Furthermore, our study showed that the expression of COX-2 was essential for BPA-induced cell migration and invasion. The results of this study provide new insights into the mechanism of endometrial cancer cell growth and invasion and potential therapeutic strategy. PMID:26546977

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

    PubMed Central

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

    2016-01-01

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

  10. Endometrial metastasis of colorectal cancer with coincident endometrial adenocarcinoma

    PubMed Central

    Colling, Richard; Lopes, Tito; Das, Nagiindra; Mathew, Joe

    2010-01-01

    Metastasis to the uterine corpus is uncommon and secondary colorectal tumours of the endometrium are rare. We describe a uterine tumour with components of both primary endometrial and metastatic colorectal carcinomata. In this case, a 72-year-old obese woman presented with a 2-week history of postmenopausal bleeding per vaginum and weight loss. She had an abdominoperineal resection 3 years previously for a Dukes stage B rectal carcinoma. A transvaginal ultrasonography showed a thickened endometrium. Histology immunophenotyping showed a CK7+, CK20+, CA125− and CEA+ colorectal metastasis (a profile consistent with her previous cancer) associated with a primary CK7+, CK20−, CA125+ and CEA− endometroid endometrial adenocarcinoma. We conclude this represents endometrial metastasis of colorectal carcinoma with coincident primary endometrial adenocarcinoma. We speculate as to whether the endometrial carcinoma arose de novo or was induced by the colorectal metastasis, or whether the primary endometrial tumour provided a fertile site for the colorectal metastasis. PMID:22791861

  11. 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…

  12. 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

  13. 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.

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

    PubMed Central

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

    2016-01-01

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

  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. microRNAs and Endometrial Pathophysiology.

    PubMed

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

    2015-01-01

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

  17. Effect of normal endometrial stroma on growth and differentiation in Ishikawa endometrial adenocarcinoma cells.

    PubMed

    Arnold, Julia T; Lessey, Bruce A; Seppälä, Markku; Kaufman, David G

    2002-01-01

    Endometrial cancer is characterized by alterations in the stromal cells and the supporting extracellular matrix in addition to the intrinsic alterations of the malignant epithelial cells. We have developed a cell culture model that demonstrates the role of stromal cells in the regulation of proliferation, hormone responsiveness, and differentiation of an endometrial adenocarcinoma cell line (Ishikawa). Conditioned medium (CM) was collected from normal primary human endometrial stromal cells grown on plastic or within the basement membrane extract, Matrigel. The CM produced by stromal cells cultured in contact with Matrigel markedly inhibited Ishikawa cell proliferation compared with CM from stromal cells cultured on plastic. Ishikawa cell proliferation varied with steroid hormone treatment in the presence of CM from stromal cells embedded in Matrigel. When the Ishikawa cells were placed in coculture in contact with stromal cells in Matrigel, production of a differentiated epithelial secretory product, glycodelin, was induced. Gene expression of stromal cell hormone receptors, growth factors, and integrins was analyzed by reverse transcription-PCR in the presence of Matrigel to determine the potential factors involved in stromal regulatory function. These combined studies imply that the phenotype of the Ishikawa cells can be induced to differentiate to more closely resemble normal endometrial epithelium by reintroduction of stromal factors and appropriate extracellular matrix. Additionally, the study shows that basement membrane proteins influence the regulatory function of stromal cells as they mediate epithelial cell growth.

  18. 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…

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

    ClinicalTrials.gov

    2009-11-13

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

  20. Persuasion Dialogues in ELT.

    ERIC Educational Resources Information Center

    Rutherford, Ramsey; Winks, Martin

    1978-01-01

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

  1. 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…

  2. 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…

  3. RANKL/RANK interaction promotes the growth of cervical cancer cells by strengthening the dialogue between cervical cancer cells and regulation of IL-8 secretion.

    PubMed

    Shang, Wen-Qing; Li, Hui; Liu, Li-Bing; Chang, Kai-Kai; Yu, Jia-Jun; Xie, Feng; Li, Ming-Qing; Yu, Jin-Jin

    2015-12-01

    Receptor activator for nuclear factor κB ligand (RANKL) is a member of the tumor necrosis factor (TNF) family. The interaction between RANKL and its receptor RANK plays an important role in the development and function of diverse tissues. However, the expression and role of RANKL in cervical cancer are still unknown. In the present study, we found that RANKL and RANK were highly co-expressed in cervical cancer. HeLa and SiHa cells secreted soluble RANKL (sRANKL), expressed member RANKL (mRANKL) and RANK. Recombinant human RANKL protein had no effect on the viability of HeLa and SiHa cells. Yet, blocking RANKL with an anti-human RANKL neutralizing antibody (α-RANKL) or recombinant human osteoprotegrin (OPG) protein resulted in the downregulation of Ki-67 and B-cell lymphoma 2 (Bcl-2) expression and an increase in Fas and Fas ligand (FasL) expression, as well as a high level of viability and a low level of apoptosis in the HeLa and SiHa cells. In addition, α-RANKL led to a decrease in IL-8 secretion. Recombinant human IL-8 protein reversed the effect of α-RANKL on the expression of proliferation- and apoptosis‑related molecules, and proliferation and apoptosis in the HeLa and SiHa cells. The present study suggests that a high level of mRANKL/RANK expression in cervical cancer lesions plays an important role in the rapid growth of cervical cancer cells possibly through strengthening the dialogue between cervical cancer cells and regulation of IL-8 secretion, which may be a possible target for cervical cancer therapy.

  4. DNA methylation in endometrial cancer

    PubMed Central

    Freudenheim, Jo L

    2010-01-01

    Endometrial cancer is the most commonly diagnosed gynecological cancer, and it has been shown to be a complex disease driven by abnormal genetic and epigenetic alterations, as well as environmental factors. Epigenetic changes resulting in aberrant gene expression are dynamic and modifiable features of many cancer types. A significant epigenetic change is aberrant DNA methylation. In this review, we review evidence on the role of aberrant DNA methylation, examining changes in relation to endometrial carcinogenesis, and report on recent advances in the understanding of the contribution of aberrant DNA methylation to endometrial cancer with the emphasis on the role of dietary/lifestyle and environmental factors, as well as opportunities and challenges of DNA methylation in endometrial cancer management and prevention. PMID:20543579

  5. 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.

  6. Peroxisome proliferator-activated receptors modulate proliferation and angiogenesis in human endometrial carcinoma.

    PubMed

    Nickkho-Amiry, Mahshid; McVey, Rhona; Holland, Cathrine

    2012-03-01

    Peroxisome proliferator-activated receptors (PPAR) and retinoid X receptors (RXR) are implicated in the development of several obesity-related cancers. Little is known of either the expression or function of PPARs and RXRs in endometrial cancer although this increasingly common disease is highly associated with both obesity and insulin resistance. We investigated the expression of PPAR and RXR subtypes in human endometrial cancers and normal endometrium with immunoblotting and immunohistochemistry and subsequently showed PPAR/RXR binding preferences by coimmunoprecipitation. To determine the functions of PPARs within the endometrium, we investigated proliferation, apoptosis, PTEN expression, and secretion of vascular endothelial growth factor (VEGF) in endometrial cell lines after reducing the expression of PPARα and PPARγ with antisense RNA. The functional effects of PPAR ligands were also investigated in vitro. We identified differential expression of PPAR and RXR subtypes in endometrial cancers and discovered that PPARγ expression correlated with expression of PTEN. PPARα activation influences endometrial cell growth and VEGF secretion. PPARγ activation reduces proliferation of endometrial cells via regulation of PTEN and appears to reduce VEGF secretion. We conclude that the PPAR/RXR pathway contribute to endometrial carcinogenesis by control of PTEN expression and modulation of VEGF secretion. We propose that PPAR ligands should be considered for clinical investigation in early phase studies of women with endometrial cancer.

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

    PubMed

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

    2013-08-19

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

  8. 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

  9. Photodynamic therapy toward selective endometrial ablation

    NASA Astrophysics Data System (ADS)

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

    1993-05-01

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

  10. 21 CFR 884.1100 - Endometrial brush.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Endometrial brush. 884.1100 Section 884.1100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL... Endometrial brush. (a) Identification. An endometrial brush is a device designed to remove samples of...

  11. 21 CFR 884.1060 - Endometrial aspirator.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Endometrial aspirator. 884.1060 Section 884.1060 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... § 884.1060 Endometrial aspirator. (a) Identification. An endometrial aspirator is a device designed...

  12. 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

  13. Adjuvant therapy for endometrial cancer

    PubMed Central

    DeLeon, Maria C.; Ammakkanavar, Natraj R.

    2014-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  15. 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…

  16. 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…

  17. 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"…

  18. The Paradox of Dialogue

    ERIC Educational Resources Information Center

    Murphy, Peter

    2011-01-01

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

  19. Dialogue in the Classroom.

    ERIC Educational Resources Information Center

    Arnett, Ronald C.

    Noting Martin Buber's rejection of both the permissive (individualistic) and the authoritative models of education and his dislike of clear epistemologies or systematic pedagogies, this paper examines Buber's work as an organized philosophical underpinning for dialogue in the classroom. The paper details Buber's approach to education as an…

  20. 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…

  1. 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)

  2. Capabilities for Intercultural Dialogue

    ERIC Educational Resources Information Center

    Crosbie, Veronica

    2014-01-01

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

  3. 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…

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

    PubMed Central

    Kiewisz, Jolanta; Wasniewski, Tomasz; Kmiec, Zbigniew

    2015-01-01

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

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

    MedlinePlus

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

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

    MedlinePlus

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

  7. Cadmium chloride alters mRNA levels of angiogenesis related genes in primary human endometrial endothelial cells grown in vitro.

    PubMed

    Helmestam, Malin; Stavreus-Evers, Anneli; Olovsson, Matts

    2010-11-01

    Cadmium, is known to cause adverse reproductive effects, and classified as an endocrine disrupting chemical (EDC). Human endometrial endothelial cells (HEEC) have a key role in the regulation of endometrial angiogenesis. These cells are known to express estrogen receptors, a feature that makes them potential targets for EDCs such as cadmium. We have designed a co-culture system, in which HEEC were grown in the same cell culture medium as endometrial stromal cells but in separate, communicating chambers. With quantitative PCR, we investigated changes in mRNA expression of genes associated with angiogenesis, sex steroids and endothelial cell specific functions. We found that cadmium altered the mRNA expression of the two important angiogenic molecules VEGF-A and PLGF. Cadmium might thus affect endometrial angiogenesis and as a consequence cause endometrial dysfunction with an increased risk for fertility problems. PMID:20580663

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

    PubMed

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

    2016-01-01

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

  9. Influence of VEGFR and LHCGR on endometrial adenocarcinoma

    PubMed Central

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

    2016-01-01

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

  10. 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

  11. Adjuvant progestagens for endometrial cancer

    PubMed Central

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

    2014-01-01

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

  12. Gene Tests May Improve Therapy for Endometrial Cancer

    MedlinePlus

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  14. 77 FR 66180 - Notice of Vacancies on the U.S. Section of the U.S.-Iraq Business Dialogue

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-02

    ... Dialogue (Business Dialogue or Dialogue) as a bilateral forum to facilitate private sector business growth... areas: --Factors that affect the growth of private sector business in Iraq, including disincentives to... regulations, to promote private sector business growth in Iraq; --Promotion of business opportunities in...

  15. Immunohistochemical expression of glypican 3 in endometrial carcinoma and correlation with prognostic parameters

    PubMed Central

    Hakim, Sarah A; Raboh, Nermine M Abd

    2015-01-01

    Background: Carcinogenesis is associated with several critical regulatory molecules which are involved in different signaling pathways such as the WNT signaling pathways. Among which the β-catenin dependent pathway has been associated with human endometrial cancer. Genetic and biochemical studies have demonstrated that glypicans can regulate several signaling pathways including those triggered by Wnts. Glypican 3 is one of six mammalian members of the glypican family of proteoglycans. Overexpression of glypican 3 has been reported in some types of cancers but only few data are available about its expression in endometrial carcinoma and its role in endometrial carcinogenesis. The aim of this study was to examine the immunohistochemical expression of glypican 3 in endometrioid endometrial carcinoma (EEC) and serous endometrial carcinoma (SEC), and to correlate its expression with prognostic factors of endometrial carcinoma. Materials and methods: Immunohistochemical expression of glypican 3 was studied in fifty two EEC and nineteen SEC cases. Results: Glypican 3 expression showed a significant difference between EEC and SEC (P = 0.027) and it was significantly correlated with tumor grade, stage and myometrial invasion (P = 0.001). Conclusion: Glypican 3 expression can be used as an adjunct in the differentiation between EEC and SEC. Glypican 3 is associated with poor prognostic parameters in both EEC and SEC, and it can be a promising molecule for targeted immunotherapy in positive cases. PMID:26722522

  16. 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.

  17. Retinoic acid inhibits endometrial cancer cell growth via multiple genomic mechanisms.

    PubMed

    Cheng, You-Hong; Utsunomiya, Hiroki; Pavone, Mary Ellen; Yin, Ping; Bulun, Serdar E

    2011-04-01

    Previous studies have indicated that retinoic acid (RA) may be therapeutic for endometrial cancer. However, the downstream target genes and pathways triggered by ligand-activated RA receptor α (RARα) in endometrial cancer cells are largely unknown. In this study, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, flow cytometry, and immunoblotting assays were used to assess the roles of RA and the RA agonist (AM580) in the growth of endometrial cancer cells. Illumina-based microarray expression profiling of endometrial Ishikawa cells incubated with and without AM580 for 1, 3, and 6 h was performed. We found that both RA and AM580 markedly inhibited endometrial cancer cell proliferation, while knockdown of RARα could block AM580 inhibition. Knockdown of RARα significantly increased proliferating cell nuclear antigen and BCL2 protein levels. Incubation of Ishikawa cells with or without AM580 followed by microarray expression profiling showed that 12 768 genes out of 47 296 gene probes were differentially expressed with significant P values. We found that 90 genes were the most regulated genes with the most significant P value (P<0.0001) using F-test. We selected four highly regulated genes with diverse functions, namely G0S2, TNFAIP2, SMAD3, and NRIP1. Real-time PCR verified that AM580 highly regulated these genes, whereas chromatin immunoprecipitation-PCR assay demonstrated that ligand-activated RARα interacted with the promoter of these genes in intact endometrial cancer cells. AM580 also significantly altered 18 pathways including those related to cell growth, differentiation, and apoptosis. In conclusion, AM580 treatment of Ishikawa cells causes the differential expression of a number of RARα target genes and activation of signaling pathways. These pathways could, therefore, mediate the carcinogenesis of human endometrial cancer.

  18. 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.

  19. Novel genetic targets in endometrial cancer

    PubMed Central

    Bell, Daphne W.

    2014-01-01

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

  20. 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.

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

    PubMed

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

    2015-11-01

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

  2. 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.

  3. Cultural Competency as Skilled Dialogue.

    ERIC Educational Resources Information Center

    Barrera, Isaura; Corso, Robert M.

    2002-01-01

    This article describes Skilled Dialogue, an approach to cultural competency developed in response to the challenges posed by cultural linguistic diversity. Skilled Dialogue focuses on cultural competency as the ability to craft respectful, reciprocal, and responsive interactions across diverse cultural parameters. Characteristics, component…

  4. 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…

  5. Jim and Dave: A Dialogue.

    ERIC Educational Resources Information Center

    Doud, Robert E.

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

  6. Classroom Dialogue and Science Achievement.

    ERIC Educational Resources Information Center

    Clarke, John A.

    This study reports the application to classroom dialogue of the Thematic and Structural Analysis (TSA) Technique which has been used previously in the analysis of text materials. The TSA Technique identifies themes (word clusters) and their structural relationship throughout sequentially organized material. Dialogues from four Year 8 science…

  7. Imre Lakatos's Use of Dialogue.

    ERIC Educational Resources Information Center

    Greig, Judith Maxwell

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

  8. Ligand-Activated Peroxisome Proliferator-activated Receptor β/δ Modulates Human Endometrial Cancer Cell Survival

    PubMed Central

    MA, JJ; Monsivais, D; Dyson, MT; Coon, JS; Malpani, S; Ono, M; Zhao, H; Xin, H; Pavone, ME; Kim, JJ; Chakravarti, D; Bulun, SE

    2013-01-01

    Endometrial cancer is the fourth most common malignancy among women and is a major cause of morbidity- contributing to approximately 8,200 annual deaths in the United States. Despite advances to the understanding of endometrial cancer, novel interventions for the disease are necessary given that many tumors become refractory to therapy. As a strategy to identify novel therapies for endometrial carcinoma, in this study we examined the contribution of the peroxisome proliferator-activated receptor β/δ (PPARβ/δ) to endometrial cancer cell proliferation and apoptosis. We found that when activated with the highly selective PPARβ/δ agonists, GW0742 and GW501516, PPARβ/δ inhibited the proliferation and markedly induced the apoptosis of three endometrial cancer cell lines. The specificity of the PPARβ/δ-induced effects on cell proliferation and apoptosis was demonstrated using PPARβ/δ-selective antagonists and PPARβ/δ siRNA in combination with PPARβ/δ-selective agonists. Furthermore, we showed that PPARβ/δ activation increased PTEN expression, which led to AKT and GSK3β dephosphorylation, and increased β-catenin phosphorylation associated with its degradation. Overall, our data suggest that the anti-tumorigenic effect of PPARβ/δ activation in endometrial cancer is mediated through the negative regulation of the AKT/GSK3β/β-catenin pathway. These findings warrant further investigation of PPARβ/δ as a therapeutic target in endometrial cancer. PMID:23943160

  9. [Biometric research in the cytomorphological diagnosis of endometrial lesions].

    PubMed

    Novik, V I; Agroskin, L S; Papaian, G V; Solov'eva, L V

    1990-01-01

    Morphometrical and optical density (including DNA content) parametres of nuclei of the endometrial epithelial cells in smears of endometrial aspirates obtained from 57 women without endometrial disorders with hyperplastic, precancer conditions and endometrial cancer have been measured by using television image analyzer IBAS-2. Biometrical data have demonstrated a good correlation with cytomorphological diagnostic criteria and in 85.7% they have facilitated discrimination of the normal and hyperplastic epithelium from precancer and high differentiated endometrial cancer. PMID:2318130

  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. Minireview: Steroid-regulated paracrine mechanisms controlling implantation.

    PubMed

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

    2014-09-01

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

  12. 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

  13. Endometrial receptivity array: Clinical application.

    PubMed

    Mahajan, Nalini

    2015-01-01

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

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

    PubMed

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

    2016-07-01

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

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

    PubMed Central

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

    2011-01-01

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

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

    ClinicalTrials.gov

    2016-10-10

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

  17. A Procedure for Analyzing Classroom Dialogue.

    ERIC Educational Resources Information Center

    Clarke, John A.

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

  18. 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…

  19. 21 CFR 884.1185 - Endometrial washer.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... with negative pressure. This device is used to study endometrial cytology (cells). (b) Classification... a recent cesarean section, and (iii) Warning: Do not attach to a wall or any external suction,...

  20. 21 CFR 884.1185 - Endometrial washer.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... with negative pressure. This device is used to study endometrial cytology (cells). (b) Classification... a recent cesarean section, and (iii) Warning: Do not attach to a wall or any external suction,...

  1. 21 CFR 884.1185 - Endometrial washer.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... with negative pressure. This device is used to study endometrial cytology (cells). (b) Classification... a recent cesarean section, and (iii) Warning: Do not attach to a wall or any external suction,...

  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... a recent cesarean section, and (iii) Warning: Do not attach to a wall or any external suction,...

  3. 21 CFR 884.1185 - Endometrial washer.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... with negative pressure. This device is used to study endometrial cytology (cells). (b) Classification... for Standardization's ISO 10993 ‘Biological Evaluation of Medical Devices—Part I: Evaluation...

  4. 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

  5. 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

  6. "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.

  7. 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

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

    PubMed

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

    2015-01-01

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

  9. AMF/PGI-mediated tumorigenesis through MAPK-ERK signaling in endometrial carcinoma.

    PubMed

    Li, Yiran; Jia, Yuanhui; Che, Qi; Zhou, Qian; Wang, Kai; Wan, Xiao-Ping

    2015-09-22

    Autocrine motility factor (AMF), which is also known as phosphoglucose isomerase (PGI), enhances tumor cell growth and motility. In this study, we found that AMF and its receptor were both highly expressed in Endometrial Carcinoma (EC) tissues compared to normal tissues. Levels of AMF were increased in serum of endometrial cancer patients. Downregulation of AMF by shRNA inhibited invasion, migration and proliferation as well as growth in a three-dimensional culture. AMF cytokine function, but not enzymatic activity of PGI, regulated tumorigenic activities of AMF. The MAPK-ERK1/2 pathway contributed to AMF-induced effects in EC cells. In agreement, Mek inhibitor decreased AMF-induced invasion, migration and proliferation of EC cells. In addition, in two mouse tumor metastasis models (EC cells delivered through left ventricle or intraperitoneally) AMF-silenced EC cells showed decreased tumor proliferative and metastatic capacities. We suggest that AMF/PGI is a potential therapeutic target in endometrial carcinoma.

  10. Endoplasmic Reticulum Stress in Endometrial Cancer

    PubMed Central

    Ulianich, Luca; Insabato, Luigi

    2014-01-01

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

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

    PubMed

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

    2016-01-22

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

  12. Addressivity in cogenerative dialogues

    NASA Astrophysics Data System (ADS)

    Hsu, Pei-Ling

    2014-03-01

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

  13. 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

  14. The dialogue goes on.

    PubMed

    Salas, R M

    1975-01-01

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

  15. Total PC Activity Is Increased in Uterine Lavage of Post-Menopausal Endometrial but Not Ovarian Cancer Patients

    PubMed Central

    Heng, Sophea; Stephens, Andrew N.; Jobling, Tom W.; Nie, Guiying

    2016-01-01

    Endometrial and ovarian cancers are two most common cancers affecting women in their post-menopausal years. To date, there are no simple biochemical tests to detect these cancers at early stages. Our previous study has demonstrated that the activity of total proprotein convertases (PCs) is significantly increased in uterine lavage at all stages of endometrial cancer, suggesting uterine lavage which can be obtained relatively non-invasively may provide a simple tool for the detection of endometrial cancer. However, uterine lavage may also contain ovarian-derived factors, and PCs are also reported to be up-regulated in ovarian cancer. In this study we determined whether increases in uterine lavage PC activity are specific to endometrial cancer or are also associated with ovarian cancer. PC activity was detected in all uterine lavages examined but no difference was found between women with and without ovarian cancer. On the other hand, the PC activity was significantly higher in post-menopausal endometrial cancer patients, consistent with our previous report. These results suggest that measuring total PC activity in uterine lavage is a useful tool to detect endometrial cancer specifically. PMID:27698920

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

    PubMed

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

    2016-06-01

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

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

    PubMed Central

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

    2006-01-01

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

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

    PubMed

    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

  19. Total PC Activity Is Increased in Uterine Lavage of Post-Menopausal Endometrial but Not Ovarian Cancer Patients

    PubMed Central

    Heng, Sophea; Stephens, Andrew N.; Jobling, Tom W.; Nie, Guiying

    2016-01-01

    Endometrial and ovarian cancers are two most common cancers affecting women in their post-menopausal years. To date, there are no simple biochemical tests to detect these cancers at early stages. Our previous study has demonstrated that the activity of total proprotein convertases (PCs) is significantly increased in uterine lavage at all stages of endometrial cancer, suggesting uterine lavage which can be obtained relatively non-invasively may provide a simple tool for the detection of endometrial cancer. However, uterine lavage may also contain ovarian-derived factors, and PCs are also reported to be up-regulated in ovarian cancer. In this study we determined whether increases in uterine lavage PC activity are specific to endometrial cancer or are also associated with ovarian cancer. PC activity was detected in all uterine lavages examined but no difference was found between women with and without ovarian cancer. On the other hand, the PC activity was significantly higher in post-menopausal endometrial cancer patients, consistent with our previous report. These results suggest that measuring total PC activity in uterine lavage is a useful tool to detect endometrial cancer specifically.

  20. 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.

  1. Three stages of medical dialogue.

    PubMed

    Abramovitch, H; Schwartz, E

    1996-06-01

    The negative consequences of physicians' failure to establish and maintain personal relationships with patients are at the heart of the "humanistic crisis" in medicine. To resolve this crisis, a new model of doctor-patient interaction is proposed, based on the ideas of Martin Buber's philosophy of dialogue. This model shows how the physician may successfully combine the personal (I-Thou) and impersonal (I-It) aspects of medicine in three stages. These "Three Stages of Medical Dialogue" include: 1. An Initial Personal Meeting stage, which initiates the doctor-patient relationship and involves mutual confirmation; 2. An Examination stage, which requires a shift from a personal to an impersonal style of interaction; 3. An Integration Through Dialogue or "Healing Through Meeting" Stage, which involves the integration of the impersonal medical data into the ongoing dialogue between doctor and patient, as a basis for shared decision-making. The use of the model, as well as common failures of doctor-patient dialogue are discussed.

  2. [Pten gene expression in the endometrial mucosa].

    PubMed

    Bakiewicz, Anna; Goździk, Jarosław; Sporny, Stanisław

    2006-04-01

    The opinions about the causes of the endometrial carcinoma have changed since 1995, due to molecular biology progress. The findings concerning the recently discovered suppressor PTEN gene localized on the chromosome 10 -10q23.3, the product of which is a specific phosphatase are especially valuable. The loss of the gene function is directly linked with the genesis and progression of endometrial carcinoma, as well as cancers of other tissues and organs, including thyroid, breast, ovary, prostate or skin. Immunohistochemical studies with the use of the 6H2.1 antibody directed against the protein coded by the PTEN gene indicate that the protein cannot be found in more than half of the patients with endometrial carcinoma and its precursor--EIN. Mutations of the PTEN gene have also been detected in many young women with normal microscopic structure of the endometrial mucosa. Thus, a test for the absence of the PTEN gene product in the endometrial cells may be used for precise identification of early stages of carcinogenesis.

  3. Fenretinide: A Novel Treatment for Endometrial Cancer

    PubMed Central

    Mittal, Navdha; Malpani, Saurabh; Dyson, Matthew; Ono, Masanori; Coon, John S.; Kim, Julie J.; Schink, Julian C.; Bulun, Serdar E.; Pavone, Mary Ellen

    2014-01-01

    Resistance to progestin treatment is a major hurdle in the treatment of advanced and reoccurring endometrial cancer. Fenretinide is a synthetic retinoid that has been evaluated in clinical trials as a cancer therapeutic and chemo-preventive agent. Fenretinide has been established to be cytotoxic to many kinds of cancer cells. In the present study, we demonstrate that fenretinide decreased cell viability and induced apoptosis in Ishikawa cells, which are an endometrial cancer cell line, in dose dependent manner in-vitro. This effect was found to be independent of retinoic acid nuclear receptor signaling pathway. Further, we have shown that this induction of apoptosis by fenretinide may be caused by increased retinol uptake via STRA6. Silencing of STRA6 was shown to decrease apoptosis which was inhibited by knockdown of STRA6 expression in Ishikawa cells. Results of an in-vivo study demonstrated that intraperitoneal injections of fenretinide in endometrial cancer tumors (created using Ishikawa cells) in mice inhibited tumor growth effectively. Immunohistochemistry of mice tumors showed a decrease in Ki67 expression and an increase in cleaved caspase-3 staining after fenretinide treatment when compared to vehicle treated mice. Collectively, our results are the first to establish the efficacy of fenretinide as an antitumor agent for endometrial cancer both in-vitro and in-vivo, providing a valuable rationale for initiating more preclinical studies and clinical trials using fenretinide for the treatment of endometrial cancer. PMID:25340777

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

    PubMed

    Gumber, Sanjeev; Springer, Nora; Wakamatsu, Nobuko

    2010-05-01

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

  5. Endometrial Stromal Nodule: Report of a Case

    PubMed Central

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

    2011-01-01

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

  6. Endometrial stromal nodule: report of a case.

    PubMed

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

    2011-01-01

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

  7. Morphometric evaluation of endometrial blood vessels.

    PubMed

    Makhija, Divya; Mathai, Alka Mary; Naik, Ramadas; Kumar, Suneet; Rai, Sharada; Pai, Muktha R; Baliga, Poornima

    2008-01-01

    Five hundred endometrial specimens were studied to document the changes in blood vessels in various phases of menstrual cycle, menstrual disturbances and in unexplained infertility. Sixty-three cases were taken as control and 437 cases as study group which included cases of dysfunctional uterine bleeding (DUB), endometrial polyps, fibroids, adenomyosis, infertility and atrophic endometrium. Using light microscopy, the vascular morphology was studied. The blood vessels were concentrated more in basal layer in the proliferative phase and in functional layer in the secretory phase. Cases of complex hyperplasia and pill endometrium had significantly higher vessel concentration. Congestion and dilatation of blood vessels were significantly higher in cases of DUB. The present study showed a positive correlation between endometrial angiogenesis and menstrual disorders. The alteration in blood vessel morphology has significant role in prognosis and in various anti-angiogenic therapies.

  8. 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

  9. Virtual Worlds and Course Dialogue

    ERIC Educational Resources Information Center

    Tapsis, Nikolaos; Tsolakidis, Konstantinos; Vitsilaki, Chryssi

    2012-01-01

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

  10. The 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…

  11. 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…

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2016-06-01

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

  15. Foxa2 Is Essential for Mouse Endometrial Gland Development and Fertility1

    PubMed Central

    Jeong, Jae-Wook; Kwak, Inseok; Lee, Kevin Y.; Kim, Tae Hoon; Large, Michael J.; Stewart, Colin L.; Kaestner, Klaus H.; Lydon, John P.; DeMayo, Francesco J.

    2010-01-01

    During embryonic development, Foxa2 is required for the formation of the node and notochord, and ablation of this gene results in defects in gastrulation, neural tube patterning, and gut morphogenesis. Foxa2 has been shown to be expressed specifically in the glandular epithelium of the murine uterus. To study the uterine function of Foxa2, this gene was conditionally ablated in the mouse uterus by crossing mice with floxed Foxa2 alleles, Foxa2loxP/loxP, with the Pgrcre mouse model. Pgrcre/+ Foxa2loxP/loxP mice showed significantly reduced fertility. Analysis of the uterus on Day 5.5 of pregnancy showed disrupted blastocyst implantation. Pgrcre/+ Foxa2loxP/loxP mice also showed a severe impairment of the uterus to respond to the artificial induction of the decidual response. Morphological examination of the uteri of these mice showed a severe reduction in the number of endometrial glands. The loss of endometrial glands resulted in the reduction of leukemia inhibitory factor (Lif) expression. The lack of a decidual response could be partially rescued by an intrauterine injection of LIF before the initiation of the decidual response. This analysis demonstrates that Foxa2 regulates endometrial gland development and that mice with a loss of endometrial glands cannot support implantation in part due to the loss of LIF, which is a requisite for fertility in the mouse. PMID:20484741

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

    PubMed Central

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

    2013-01-01

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

  17. Laparoscopic surgery for endometrial cancer: a review.

    PubMed

    Hauspy, Jan; Jiménez, Waldo; Rosen, Barry; Gotlieb, Walter H; Fung-Kee-Fung, Michael; Plante, Marie

    2010-06-01

    Uterine cancer is the fourth most common cancer in Canadian women, with an estimated 4200 new cases and 790 disease-related deaths in 2008. We investigated the domains that are important for further implementation of minimally invasive surgery for the management of endometrial cancer by performing a literature review to assess the available data on overall and disease-free survival in laparoscopic versus open surgery. We also investigated the influence of patient- related factors, surgical factors, quality of life, and cost implications. Among the 23 articles reviewed, five were randomized controlled trials (RCTs), four were prospective reviews, and 14 were retrospective reviews. The RCTs showed no difference in overall and disease-free survival for patients with endometrial cancer who had undergone laparoscopic hysterectomy compared with open surgery. Morbid obesity is a limiting factor for the feasibility of complete laparoscopic staging. Laparoscopy seems to decrease complications and decrease blood loss. It also shortens hospital stay, with improved short-term quality of life and cosmesis, while yielding similar lymph node counts. Overall, laparoscopy is cost-effective, because the increased operation cost of laparoscopy is offset by the shorter hospital stay and faster return to work. On the basis of currently available data, patients with endometrial cancer should be offered minimally invasive surgery as part of their treatment for endometrial cancer whenever possible.

  18. Stimulatory Effect of Vascular Endothelial Growth Factor on Proliferation and Migration of Porcine Trophectoderm Cells and Their Regulation by the Phosphatidylinositol-3-Kinase-AKT and Mitogen-Activated Protein Kinase Cell Signaling Pathways.

    PubMed

    Jeong, Wooyoung; Kim, Jinyoung; Bazer, Fuller W; Song, Gwonhwa

    2014-03-01

    Vascular endothelial growth factor (VEGF), a potent stimulator for angiogenesis, is likely to regulate implantation by stimulating endometrial angiogenesis and vascular permeability. In addition to known angiogenetic effects, VEGF has been suggested to participate in development of the early embryo as a mediator of fetal-maternal dialogue. Current studies have determined VEGF in terms of its role in endometrial vascular events, but VEGF-induced effects on the peri-implantation conceptus (embryo and extraembryonic membranes) remains unknown. In the present study, endometrial VEGF, VEGF receptor-1 (VEGFR-1), and VEGF receptor-2 (VEGFR-2) mRNAs increased significantly during the peri-implantation period of pregnancy as compared to the estrous cycle. Expression of VEGF, VEGFR-1, and VEGFR-2 mRNAs was abundant in endometrial luminal and glandular epithelia, endothelial blood vessels, and scattered cells in the stroma and conceptus trophectoderm. In addition, porcine trophectoderm (pTr) cells treated with VEGF exhibited increased abundance of phosphorylated (p)-AKT1, p-ERK1/2, p-p70RSK, p-RPS6, and p-4EBP1 in a time-dependent manner. The addition of U0126, an inhibitor of ERK1/2, inhibited VEGF-induced ERK1/2 phosphorylation, but AKT1 phosphorylation was not affected. The addition of LY294002, a PI3K inhibitor, decreased VEGF-induced phosphorylation of ERK1/2 and AKT1. Furthermore, VEGF significantly stimulated proliferation and migration of pTr cells, but these effects were blocked by SB203580, U0126, rapamycin, and LY294002, which inhibit p38 MAPK, ERK1/2, mTOR, and PI3K, respectively. These results suggest that VEGF is critical to successful growth and development of pTr during early pregnancy and that VEGF-induced stimulatory effect is coordinately regulated by multiple cell signaling pathways, including PI3K-AKT1 and MAPK signaling pathways. PMID:24451985

  19. 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

  20. The role of colony-stimulating factor 1 and its receptor in the etiopathogenesis of endometrial adenocarcinoma.

    PubMed

    Smith, H O; Anderson, P S; Kuo, D Y; Goldberg, G L; DeVictoria, C L; Boocock, C A; Jones, J G; Runowicz, C D; Stanley, E R; Pollard, J W

    1995-03-01

    Colony-stimulating factor 1 (CSF-1) is a homodimeric growth factor that humorally regulates the growth and differentiation of mononuclear phagocytes, and locally regulates maternal-fetal interactions during pregnancy. It exerts these actions through a transmembrane tyrosine kinase receptor, colony-stimulating factor 1 receptor (CSF-1R), the product of the c-fms proto-oncogene. Recent studies have demonstrated overexpression of CSF-1 and its receptor in breast, ovarian, and endometrial adenocarcinomas. To further investigate the possible role of CSF-1 and its receptor in the pathogenesis of endometrial adenocarcinoma, a prospective study was undertaken to study CSF-1 expression in benign and neoplastic endometrial epithelium and to compare serum CSF-1 levels in endometrial adenocarcinoma patients with healthy perimenopausal women. The mean serum levels of CSF-1 in 71 patients with endometrial cancer (4.9 +/- 1.8 microgram/liter) were significantly elevated compared with levels found in the 32 controls (3.5 +/- 1.1 microgram/liter). Within the endometrial adenocarcinoma group, circulating CSF-1 levels were significantly elevated in patients with large tumor volume, high grade, myometrial invasion, residual disease, and circulating CA-125 levels. High serum levels of serum CSF-1 were associated with elevated serum CA19-9 and CA-125 levels. Immunohistochemistry results revealed in tumor epithelium intense staining for CSF-1R (27 of 54 cases, 50%) and elevated staining for CSF-1 (41 of 54 cases, 75.9%), with intense staining of CSF-1 in 16 of 54 cases (29.6%). Staining was significantly greater in intensity and number of cells involved in malignant compared with benign epithelium for CSF-1R and CSF-1 (P = 0.05 and <0.0001, respectively). A positive correlation between amount and intensity of CSF-1 and CSF-1R staining in endometrial adenocarcinoma tissue was also demonstrated (P = 0.007). CSF-1 and CSF-1R mRNA was also detected in the tumor samples, confirming the

  1. Figure analysis: An implementation dialogue.

    PubMed

    Wiles, Amy M

    2016-07-01

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

  2. Figure analysis: An implementation dialogue.

    PubMed

    Wiles, Amy M

    2016-07-01

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

  3. 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. PMID:27629137

  4. The expression pattern of MUC1 glycoforms and other biomarkers of endometrial receptivity in fertile and infertile women.

    PubMed

    Horne, A W; Lalani, E-N; Margara, R A; Ryder, T A; Mobberley, M A; White, J O

    2005-10-01

    Changes in the surface epithelium of the endometrium, characterized in part by alterations in cell-surface molecules, sex steroid receptors and the appearance of pinopodes, coincide with the window of endometrial receptivity in the menstrual cycle. This study was performed to evaluate the usefulness of hematoxylin and eosin staining, scanning and transmission microscopy, and MUC1 glycoform, sex steroid receptor, and interleukin receptor (type 1) expression as biomarkers of endometrial receptivity using carefully characterized clinical fertile and infertile groups of women. Using a combination of immunohistochemistry and scanning electron microscopy (SEM) called scanning immunoelectron microscopy (SIM), we confirmed that MUC1 mucin was not associated with the endometrial pinopodes, which have been linked with embryo adhesion. We also showed that failure of embryo implantation was associated with an abnormal endometrial expression of MUC1 mucin, and retention of nuclear progesterone receptor (PR) particularly in epithelial cells. Hematoxylin and eosin staining, transmission electron microscopy (TEM), SEM in isolation and immunohistochemistry for interleukin receptor were not shown to be useful markers. Progesterone-dependent regulation of MUC1 appears to be an important factor in determining endometrial receptivity.

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

    PubMed Central

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

    2014-01-01

    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 =3.4 ± 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. PMID:24270393

  6. 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.

  7. 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

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

    PubMed

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

    2016-03-01

    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.

  9. 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

  10. 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.

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

    PubMed

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

    2016-03-01

    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

  12. 75 FR 13284 - Pesticide Program Dialogue Committee; Request for Nominations to the Pesticide Program Dialogue...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-19

    ... AGENCY Pesticide Program Dialogue Committee; Request for Nominations to the Pesticide Program Dialogue Committee AGENCY: Environmental Protection Agency (EPA). ACTION: Notice. SUMMARY: Pursuant to the Federal Advisory Committee Act, EPA's Office of Pesticide Programs is inviting nominations of qualified...

  13. My approach to the interpretation of endometrial biopsies and curettings

    PubMed Central

    McCluggage, W G

    2006-01-01

    A major proportion of the workload in many histopathology laboratories is accounted for by endometrial biopsies, either curettage specimens or outpatient biopsy specimens. The increasing use of pipelle and other methods of biopsy not necessitating general anaesthesia has resulted in greater numbers of specimens with scant tissue, resulting in problems in assessing adequacy and in interpreting artefactual changes, some of which appear more common with outpatient biopsies. In this review, the criteria for adequacy and common artefacts in endometrial biopsies, as well as the interpretation of endometrial biopsies in general, are discussed, concentrating on areas that cause problems for pathologists. An adequate clinical history, including knowledge of the age, menstrual history and menopausal status, and information on the use of exogenous hormones and tamoxifen, is necessary for the pathologist to critically evaluate endometrial biopsies. Topics such as endometritis, endometrial polyps, changes that are induced by hormones and tamoxifen within the endometrium, endometrial metaplasias and hyperplasias, atypical polypoid adenomyoma, adenofibroma, adenosarcoma, histological types of endometrial carcinoma and grading of endometrial carcinomas are discussed with regard to endometrial biopsy specimens rather than hysterectomy specimens. The value of ancillary techniques, especially immunohistochemistry, is discussed where appropriate. PMID:16873562

  14. [Molecular based targets and endometrial cancer].

    PubMed

    Stoyanov, St; Ananiev, J; Ivanova, K; Velev, V; Todorova, M; Gulubova, M

    2015-01-01

    In recent years, increasing attention has been paid to the rate of spread of endometrial carcinoma, especially in the postmenopausal period. Along with routine diagnostic methods, giving information on the location and progression of the disease, there are some morphological methods determining very accurately the correlations in the development of this type of cancer and his prognosis. Moreover--in recent years, the accumulated information about the molecular profile of this type of cancer made it possible to implement a number of new drugs against the so-called molecular therapy -'targets' in the neoplastic process. Significant proportion of cases show response rates, it is more hope in the development of more successful formulas and target -based therapy. In this review, we present and discuss the role of certain molecular markers as potential indicators of prognosis and development, as well as determining the target treatment of endometrial carcinoma.

  15. [Molecular based targets and endometrial cancer].

    PubMed

    Stoyanov, St; Ananiev, J; Ivanova, K; Velev, V; Todorova, M; Gulubova, M

    2015-01-01

    In recent years, increasing attention has been paid to the rate of spread of endometrial carcinoma, especially in the postmenopausal period. Along with routine diagnostic methods, giving information on the location and progression of the disease, there are some morphological methods determining very accurately the correlations in the development of this type of cancer and his prognosis. Moreover--in recent years, the accumulated information about the molecular profile of this type of cancer made it possible to implement a number of new drugs against the so-called molecular therapy -'targets' in the neoplastic process. Significant proportion of cases show response rates, it is more hope in the development of more successful formulas and target -based therapy. In this review, we present and discuss the role of certain molecular markers as potential indicators of prognosis and development, as well as determining the target treatment of endometrial carcinoma. PMID:25909140

  16. Endometrial cancer: Not your grandmother's cancer.

    PubMed

    McAlpine, Jessica N; Temkin, Sarah M; Mackay, Helen J

    2016-09-15

    Worldwide, the incidence of endometrial carcinoma (EC) is rapidly increasing, and the highest disease burden is reported in North America and Western Europe. Although the prognosis remains good for patients with are diagnosed with early stage EC, for those with recurrent or metastatic disease, the options are few, and the median overall survival is short. It is imperative to gain a greater understanding of all aspects of EC, limit its effect on scarce health care resources and, more importantly, prevent this cancer from significantly impacting future generations of women. An exciting new era of endometrial cancer research and clinical management has begun that incorporates biologically and clinically relevant genomic and clinicopathologic parameters. Continued collaborative research efforts and funding are essential if we are to advance our understanding of this disease and improve clinical outcomes. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2787-2798. © 2016 American Cancer Society. PMID:27308732

  17. Endometrial cancer: rising incidence, detection and treatment.

    PubMed

    Kistner, R W; Krantz, K E; Lebherz, T B; Lewis, G L; Reagan, J W; Smith, J; Tobin, J J; Wied, G L

    1973-02-01

    This editorial consists of summaries of the discussions on incidence, pathogenesis, prognosis and patient follow-up, and transcripts of the discussions on detection and treatment of endometrial carcinoma, from a symposium held in Carefree, Arizona. 75% of the cancers occur in postmenopausal women; average age is 52 years, but is decreasing. Endometrial carcinoma rose from 20.3 to 46.3% of all uterine cancers in Cleveland University Hospitals from 1941-1970. Older patients are often diabetic, overweight, nulliparous, with anovulatory or familial history; young women frequently resemble mild Stein-Levinthal syndrome. Clinically, 20% of patients are assymptomatic, others may have softer or larger uterus, larger ovaries, irregular postmenopausal bleeding, or lengthy onset of menopause. The Gravlee jet wash is indicated for high risk patients and those about to take estrogen. Endometrial carcinoma first affects epithelium, then endometrial stroma, then upper myometrium, lower myometrium, then other organs, perhaps via lymphatics, vagina, tubes, but ascites is uncommon. Generally, U.S. physicians use intrauterine radium followed by surgery, British use surgery first, and Swedish use radiation only. Cases must be treated individually, e.g. surgery only for minimal cancer, radium and surgery for more serious cases, and preoperative external radiation also for advanced disease. Although radiation lessens chance of implantation during surgical trauma, insertion of intrauterine radium enhances spread of tumor cells. Injectable progestins sometimes control metastatic disease, although they require 8 weeks to act. Progestins may help those with late recurrence, squamous metaplasia, or who are under 50 years of age. Estrogens are rarely effective. Prognois for terminal patients often includes subjective improvement, bowel obstruction, lung complications, hemorrhage. Radiation side effects and menopausal symptoms are often problems for cured patients. In young cured patients the

  18. Integrated genomic characterization of endometrial carcinoma.

    PubMed

    Kandoth, Cyriac; Schultz, Nikolaus; Cherniack, Andrew D; Akbani, Rehan; Liu, Yuexin; Shen, Hui; Robertson, A Gordon; Pashtan, Itai; Shen, Ronglai; Benz, Christopher C; Yau, Christina; Laird, Peter W; Ding, Li; Zhang, Wei; Mills, Gordon B; Kucherlapati, Raju; Mardis, Elaine R; Levine, Douglas A

    2013-05-01

    We performed an integrated genomic, transcriptomic and proteomic characterization of 373 endometrial carcinomas using array- and sequencing-based technologies. Uterine serous tumours and ∼25% of high-grade endometrioid tumours had extensive copy number alterations, few DNA methylation changes, low oestrogen receptor/progesterone receptor levels, and frequent TP53 mutations. Most endometrioid tumours had few copy number alterations or TP53 mutations, but frequent mutations in PTEN, CTNNB1, PIK3CA, ARID1A and KRAS and novel mutations in the SWI/SNF chromatin remodelling complex gene ARID5B. A subset of endometrioid tumours that we identified had a markedly 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 affect post-surgical adjuvant treatment for women with aggressive tumours.

  19. The epidemiology of endometrial and ovarian cancer.

    PubMed

    Cramer, Daniel W

    2012-02-01

    This review highlights similarities in the epidemiology of endometrial and ovarian cancer, including highly correlated incidence rates and similar risk factor profiles. Factors that decrease risk for both cancers include a late menarche, early age at first birth, giving birth and breastfeeding, and use of oral contraceptives. Short or irregular cycles and late menopause are associated with increased risk for both. Other risk factors that appear to operate in a similar direction include decreased risk associated with IUD use or a tubal ligation, and increased risk associated with obesity, lack of exercise, and use of talc powders in genital hygiene. Estrogen excess is proposed as the underlying mechanism for most endometrial cancers, whereas incessant ovulation has been suggested as the explanation for ovarian cancer. However, an increased number of estimated ovulatory cycles correlates directly with risk for both endometrial and ovarian cancer, suggesting that reproductive tissue turnover with an accumulation of PTEN or p53 mutations represents a possible common mechanism. An immune-based explanation involving mucin proteins represents another common mechanism that could explain additional risk factors. Maintenance of ideal weight, breastfeeding children, use of oral contraceptives, and avoidance of talc powders in genital hygiene are measures that could lower the risk for both types of cancer. Careful selection of patients for prophylactic oophorectomy for those women who are coming to hysterectomy for benign disease is an additional measure to consider for ovarian cancer.

  20. Endometrial transcriptional profiling of a bovine fertility model by Next-Generation Sequencing

    PubMed Central

    Mesquita, F.S.; Ramos, R.S.; Pugliesi, G.; Andrade, S.C.S.; Van Hoeck, V.; Langbeen, A.; Oliveira, M.L.; Gonella-Diaza, A.M.; Gasparin, G.; Fukumasu, H.; Pulz, L.H.; Membrive, C.M.; Coutinho, L.L.; Binelli, M.

    2015-01-01

    Studying the multitude of molecular networks and pathways that are potentially involved in a complex trait such as fertility requires an equally complex and broad strategy. Here, we used Next-Generation Sequencing for the characterization of the transcriptional signature of the bovine endometrial tissue. Periovulatory endocrine environments were manipulated to generate two distinctly different fertility phenotypes. Cycling, non-lactating, multiparous Nelore cows were manipulated to ovulate larger (> 13 mm; LF group; high fertility phenotype) or smaller (< 12 mm; SF group) follicles. As a result, greater proestrus estrogen concentrations, corpora lutea and early diestrus progesterone concentrations were also observed in LF group in comparison to SF group. Endometrial cell proliferation was estimated by the protein marker MKI67 on tissues collected 4 (D4) and 7 (D7) days after induction of ovulation. Total RNA extracts from D7 were sequenced and compared according to the transcriptional profile of each experimental group (LF versus SF). Functional enrichment analysis revealed that LF and SF endometria were asynchronous in regards to their phenotype manifestation. Major findings indicated an LF endometrium that was switching phenotypes earlier than the SF one. More specifically, a proliferating SF endometrium was observed on D7, whereas the LF tissue, which expressed a proliferative phenotype earlier at D4, seemed to have already shifted towards a biosynthetically and metabolically active endometrium on D7. Data on MKI67 support the transcriptomic results. RNA-Seq-derived transcriptional profile of the endometrial tissue indicated a temporal effect of the periovulatory endocrine environment, suggesting that the moment of the endometrial exposure to the ovarian steroids, E2 and P4, regulates the timing of phenotype manifestation. Gene expression profiling revealed molecules that may be targeted to elucidate ovarian steroid-dependent mechanisms that regulate

  1. The clock protein period 2 synchronizes mitotic expansion and decidual transformation of human endometrial stromal cells.

    PubMed

    Muter, Joanne; Lucas, Emma S; Chan, Yi-Wah; Brighton, Paul J; Moore, Jonathan D; Lacey, Lauren; Quenby, Siobhan; Lam, Eric W-F; Brosens, Jan J

    2015-04-01

    Implantation requires coordinated interactions between the conceptus and surrounding decidual cells, but the involvement of clock genes in this process is incompletely understood. Circadian oscillations are predicated on transcriptional-translational feedback loops, which balance the activities of the transcriptional activators CLOCK (circadian locomotor output cycles kaput) and brain muscle arnt-like 1 and repressors encoded by PER (Period) and Cryptochrome genes. We show that loss of PER2 expression silences circadian oscillations in decidualizing human endometrial stromal cells (HESCs). Down-regulation occurred between 12 and 24 hours following differentiation and coincided with reduced CLOCK binding to a noncanonical E-box enhancer in the PER2 promoter. RNA sequencing revealed that premature inhibition of PER2 by small interfering RNA knockdown leads to a grossly disorganized decidual response. Gene ontology analysis highlighted a preponderance of cell cycle regulators among the 1121 genes perturbed upon PER2 knockdown. Congruently, PER2 inhibition abrogated mitotic expansion of differentiating HESCs by inducing cell cycle block at G2/M. Analysis of 70 midluteal endometrial biopsies revealed an inverse correlation between PER2 transcript levels and the number of miscarriages in women suffering reproductive failure (Spearman rank test, ρ = -0.3260; P = 0.0046). Thus, PER2 synchronizes endometrial proliferation with initiation of aperiodic decidual gene expression; uncoupling of these events may cause recurrent pregnancy loss. PMID:25573754

  2. Long Non-Coding RNAs in Endometrial Carcinoma.

    PubMed

    Smolle, Maria A; Bullock, Marc D; Ling, Hui; Pichler, Martin; Haybaeck, Johannes

    2015-11-04

    Endometrial carcinoma (EC), the second most common form of gynaecological malignancy, can be divided into two distinct sub-types: Type I tumours arise from hyperplastic endometrium and typically effect women around the time of menopause, whereas type II tumours arise in postmenopausal women from atrophic endometrium. Long non-coding RNAs (lncRNAs) are a novel class of non-protein coding molecules that have recently been implicated in the pathogenesis of many types of cancer including gynaecological tumours. Although they play critical physiological roles in cellular metabolism, their expression and function are deregulated in EC compared with paired normal tissue, indicating that they may also participate in tumour initiation and progression. For instance, the lncRNA MALAT-1 is down-regulated in EC samples compared to normal or hyperplastic endometrium, whereas the lncRNA OVAL is down-regulated in type II disease but up-regulated in type I disease. Other notatble lncRNAs such as HOTAIR, H19 and SRA become up-regulated with increasing EC tumour grade and other features associated with poor prognosis. In the current review, we will examine the growing body of evidence linking deregulated lncRNAs with specific biological functions of tumour cells in EC, we will highlight associations between lncRNAs and the molecular pathways implicated in EC tumourigenesis and we will identify critical knowledge gaps that remain to be addressed.

  3. Long Non-Coding RNAs in Endometrial Carcinoma

    PubMed Central

    Smolle, Maria A.; Bullock, Marc D.; Ling, Hui; Pichler, Martin; Haybaeck, Johannes

    2015-01-01

    Endometrial carcinoma (EC), the second most common form of gynaecological malignancy, can be divided into two distinct sub-types: Type I tumours arise from hyperplastic endometrium and typically effect women around the time of menopause, whereas type II tumours arise in postmenopausal women from atrophic endometrium. Long non-coding RNAs (lncRNAs) are a novel class of non-protein coding molecules that have recently been implicated in the pathogenesis of many types of cancer including gynaecological tumours. Although they play critical physiological roles in cellular metabolism, their expression and function are deregulated in EC compared with paired normal tissue, indicating that they may also participate in tumour initiation and progression. For instance, the lncRNA MALAT-1 is down-regulated in EC samples compared to normal or hyperplastic endometrium, whereas the lncRNA OVAL is down-regulated in type II disease but up-regulated in type I disease. Other notatble lncRNAs such as HOTAIR, H19 and SRA become up-regulated with increasing EC tumour grade and other features associated with poor prognosis. In the current review, we will examine the growing body of evidence linking deregulated lncRNAs with specific biological functions of tumour cells in EC, we will highlight associations between lncRNAs and the molecular pathways implicated in EC tumourigenesis and we will identify critical knowledge gaps that remain to be addressed. PMID:26556343

  4. Significance and Dialogue in Learning and Teaching

    ERIC Educational Resources Information Center

    Metcalfe, Andrew; Game, Ann

    2008-01-01

    In this essay Andrew Metcalfe and Ann Game argue that although the term "dialogue" is commonly used in educational theory, its full significance is diluted if it is seen as a matter of exchange or negotiation of prior positions and identities. As a meeting point, they argue, dialogue suspends the senses of time, space, and ontology on which…

  5. Dialogue in a Distance Education Physics Course

    ERIC Educational Resources Information Center

    Gorsky, Paul; Caspi, Avner; Trumper, Ricardo

    2004-01-01

    This study investigated the kinds of dialogues utilized by Open University students while studying an intermediate level physics course. Research objectives were twofold: to document what dialogue types, mediated through which resources, were (1) generally utilized by students as they learned; and (2) were specifically utilized by students to…

  6. Instructional Dialogue: Distance Education Students' Dialogic Behaviour

    ERIC Educational Resources Information Center

    Caspi, Avner; Gorsky, Paul

    2006-01-01

    Instructional systems, both distance education and campus-based, may be viewed in terms of intrapersonal and interpersonal "instructional dialogues," that mediate and facilitate learning respectively, and "instructional resources" that enable such dialogues. Resources include self-instruction texts, tutorials, instructor availability, websites and…

  7. 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…

  8. Using Dialogue Journals to Focus on Form

    ERIC Educational Resources Information Center

    Linnell, Kimberly Miller

    2010-01-01

    Dialogue journals have been used in a wide range of educational settings for quite some time. These written conversations between teachers and students are especially well suited for the ESL classroom. This article describes how many of the conditions known to foster second language acquisition are inherent in the dialogue journal. Traditionally,…

  9. Dialogue as a Site of Transformative Possibility

    ERIC Educational Resources Information Center

    Sinha, Shilpi

    2010-01-01

    This article examines how affect allows us to view the relational form of dialogue, as built upon the work of Derrida and Levinas, to be a site of transformative possibility for students as they encounter and address issues of social justice and difference in the classroom. The understanding of affect that attends this form of dialogue demands…

  10. 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…

  11. Metaphors of Literacy: Dialogues in Inclusive Settings

    ERIC Educational Resources Information Center

    Causarano, Antonio

    2015-01-01

    This article discusses the importance of metaphors in education and in inclusive settings in particular. Metaphors are seen as the fabric of collaboration through dialogue across the curriculum. The article analyzes the dialogues among the Language Arts, Social Studies, and inclusion teacher in a large middle school in the Southwest of the United…

  12. Mapping Mentor Teachers' Roles in Mentoring Dialogues

    ERIC Educational Resources Information Center

    Hennissen, Paul; Crasborn, Frank; Brouwer, Niels; Korthagen, Fred; Bergen, Theo

    2008-01-01

    This literature study deals with the issue of how to conceptualize the supervisory behaviour of mentor teachers in mentoring dialogues by systematically examining empirical literature on key aspects of mentor teachers' behaviour during dialogues with prospective teachers. From the findings a model is derived which can be used to study mentor…

  13. 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…

  14. 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…

  15. Listening in on Monologues and Dialogues.

    ERIC Educational Resources Information Center

    Tree, Jean E. Fox

    1999-01-01

    Compares the communicative effectiveness of spontaneous monologues and dialogues on nonparticipating addressees overhearing talk. Finds that overhearers were more accurate at following instructions in a referential communication task when listening in on dialogues than when listening in on monologues. Suggests greater number of discourse markers…

  16. 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…

  17. 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:…

  18. 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.

  19. 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.

  20. Systemic therapy for endometrial stromal sarcomas: current treatment options.

    PubMed

    Serkies, Krystyna; Pawłowska, Ewa; Jassem, Jacek

    2016-01-01

    Uterine endometrial stromal sarcomas including true low-grade endometrial stromal sarcoma (LG-ESS) and high-grade (HG-ESS) or undifferentiated endometrial sarcoma (UES) constitute a group of rare, aggressive malignancies. Most LG-ESSs express steroid receptors. Surgery is the principal primary therapy for endometrial stromal sarcomas and should be considered in all cases. These malignancies are relatively radio- and chemoresistant. Chemotherapy is used in recurrent and advanced HG-ESS and UES. Currently, the combination of gemcitabine and docetaxel is considered the most effective regimen, but at the expense of substantial toxicity. In steroid receptor positive advanced LG-ESS hormonal therapy, mainly with progestins, allows in some patients for a long-term survival. Aromatase inhibitors seem to be equally effective as first- and subsequent-line of treatment, and are well tolerated. The role of molecular-targeted therapies in endometrial stromal sarcomas remains to be established. PMID:27629136

  1. Clear cell adenocarcinoma present exclusively within endometrial polyp: report of two cases.

    PubMed

    Ishida, Mitsuaki; Iwai, Muneo; Yoshida, Keiko; Kagotani, Akiko; Okabe, Hidetoshi

    2014-01-01

    Endometrial polyp is a common benign lesion that protrudes into the endometrial surface. The incidence of carcinoma within endometrial polyp is thought to be low, however, postmenopausal women with endometrial polyps are at an increased risk. Endometrial clear cell adenocarcinoma is a distinct and relatively rare subtype of endometrial carcinoma, and recent studies have proposed putative precursor lesions of clear cell adenocarcinoma, namely clear cell endometrial glandular dysplasia (EmGD) and clear cell endometrial intraepithelial carcinoma (EIC). Herein, we describe two cases of clear cell adenocarcinoma present exclusively within endometrial polyp and discuss the association of its precursor. Two postmenopausal Japanese females, 66-year-old (Case 1) and 54-year-old (Case 2) presented with abnormal genital bleeding. Cytological examination of both cases revealed adenocarcinoma, thus, hysterectomy was performed. Histopathological studies demonstrated clear cell adenocarcinoma within exclusively endometrial polyp in both cases. The peculiar finding in Case 1 was presence of atypical glandular cells with large round to oval nuclei and clear cytoplasm within the atrophic endometrial glands in the surrounding endometrial tissue, which corresponded to clear cell EIC. A recent study showed that 33% of uteri had at least one focus of clear cell EmGD in endometrial polyps. Accordingly, clear cell adenocarcinoma and clear cell EmGD can occur in association with endometrial polyps more frequently than previously thought. Therefore, detailed histopathological examination is important in diagnosis of endometrial polyps, especially in the postmenopausal women, moreover cytological examination is a useful tool in the postmenopausal women with endometrial polyps.

  2. Expression of retinoic acid receptors in human endometrial carcinoma.

    PubMed

    Tanabe, Kojiro; Utsunomiya, Hiroki; Tamura, Mitsutoshi; Niikura, Hitoshi; Takano, Tadao; Yoshinaga, Kohsuke; Nagase, Satoru; Suzuki, Takashi; Ito, Kiyoshi; Matsumoto, Mitsuyo; Hayashi, Shin-ichi; Yaegashi, Nobuo

    2008-02-01

    The retinoids (vitamin A and its biologically active derivatives) are essential for the health and survival of the individual. Several studies have reported a strong rationale for the use of retinoids in cancer treatment and chemoprevention. It has been discovered that expression of retinoic acid receptor (RAR) beta is frequently silenced in epithelial carcinogenesis, which has led to the hypothesis that RAR beta could act as a tumor suppressor. However, the status of RAR beta in human endometrial carcinoma has not been examined. In the present study, we initially studied the effects of retinoic acid on cell proliferation and the expression of RAR alpha, RAR beta, and RAR gamma using AM580 (a RAR-specific agonist) in the Ishikawa endometrial cancer cell line. We also examined the expression of RAR in human eutopic endometrium (30 cases), endometrial hyperplasia (28 cases), and endometrial carcinoma (103 cases) using immunohistochemistry. Finally, we correlated these findings with the clinicopathological parameters. In vitro, cell growth was inhibited and RAR beta and RAR gamma mRNA was significantly induced by AM580, compared with vehicle controls, whereas RAR alpha mRNA was significantly attenuated by AM580, compared with vehicle. RAR beta was detected predominantly in endometrial hyperplasia, compared with endometrial carcinoma. No statistically significant correlation was obtained between the expression of any other RAR subtypes and clinicopathological parameters in human endometrial carcinoma. The results of our study demonstrate that AM580 inhibits cell growth and induces RAR beta mRNA expression in the Ishikawa cell line, and the expression level of RAR beta in endometrial carcinoma is significantly lower than that in endometrial hyperplasia. AM580 might therefore be considered as a potential treatment for endometrial carcinoma.

  3. 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.

  4. Endometrial carcinoma in a young dog.

    PubMed

    Payne-Johnson, C E; Kelly, D F; Davies, P T

    1986-07-01

    A 2-years-old nulliparous cross-bred bitch had persistent vulval discharge following treatments that included a combined ethinyloestradiol/methyltestosterone preparation and megoestrol acetate. The uterus, removed at ovarohysterectomy, contained a large polypoid intraluminal mass with the histological features of endometrial carcinoma. The bitch has remained well for thirty-one months after surgery. The possibility is considered that the lesion is drug-related but no firm conclusion can be drawn about the precise nature and pathogenesis of this unusual lesion.

  5. Isolated humeral recurrence in endometrial carcinoma.

    PubMed

    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

  6. 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

  7. The role of Lipoxin A4 in endometrial biology and endometriosis

    PubMed Central

    Canny, GO; Lessey, BA

    2014-01-01

    Lipoxin A4 (LXA4), an endogenous anti-inflammatory and immunomodulatory mediator studied in many disease states, is recently appreciated as a potentially significant player in the endometrium. This eicosanoid, synthesized from arachidonic acid via the action of lipoxygenase enzymes, is likely regulated in endometrial tissue during the menstrual cycle. Recent studies revealed that LXA4 acts as an estrogen receptor agonist in endometrial epithelial cells, antagonizing some estrogen-mediated activities in a manner similar to the weak estrogen estriol, with which it shares structural similarity. LXA4 may also be an anti-inflammatory molecule in the endometrium, though its precise function in various physiological and pathological scenarios remains to be determined. The expression patterns for LXA4 and its receptor in the female reproductive tract suggest a role in pregnancy. The present review provides an oversight of its known and putative roles in the context of immuno-endocrine crosstalk. Endometriosis, a common inflammatory condition and a major cause of infertility and pain, is currently treated by surgery or anti-hormone therapies that are contraceptive and associated with undesirable side effects. LXA4 may represent a potential therapeutic and further research to elucidate its function in endometrial tissue and the peritoneal cavity will undoubtedly provide valuable insights. PMID:23485944

  8. Growth factor induced proliferation, migration, and lumen formation of rat endometrial epithelial cells in vitro

    PubMed Central

    ISLAM, Md. Rashedul; YAMAGAMI, Kazuki; YOSHII, Yuka; YAMAUCHI, Nobuhiko

    2016-01-01

    Endometrial modulation is essential for the preservation of normal uterine physiology, and this modulation is driven by a number of growth factors. The present study investigated the mitogenic, motogenic, and morphogenic effects of epidermal growth factor (EGF) and hepatocyte growth factor (HGF) on rat endometrial epithelial (REE) cells. The REE cells were isolated and cultured and then characterized based on their morphology and their expression of epithelial cell markers. The MTT assay revealed that EGF and HGF induce proliferation of REE cells. Consistent with increased proliferation, we found that the cell cycle regulatory factor Cyclin D1 was also upregulated upon EGF and HGF addition. REE cell migration was prompted by EGF, as observed with the Oris Cell Migration Assay. The morphogenic impact of growth factors on REE cells was studied in a three-dimensional BD Matrigel cell culture system, wherein these growth factors also increased the frequency of lumen formation. In summary, we show that EGF and HGF have a stimulatory effect on REE cells, promoting proliferation, cell migration, and lumen formation. Our findings provide important insights that further the understanding of endometrial regeneration and its regulation. PMID:26946922

  9. Lipocalin 2 Enhances Migration and Resistance against Cisplatin in Endometrial Carcinoma Cells

    PubMed Central

    Kashima, Hiroyasu; Yamada, Yasushi; Kobara, Hisanori; Asaka, Ryoichi; Ando, Hirofumi; Higuchi, Shotaro; Ida, Koichi; Mvunta, David Hamisi; Shiozawa, Tanri

    2016-01-01

    Purpose Lipocalin 2 (LCN2) is a secretory protein that is involved in various physiological processes including iron transport. We previously identified LCN2 as an up-regulated gene in endometrial carcinoma, and found that the overexpression of LCN2 and its receptor, SLC22A17, was associated with a poor prognosis. However, the functions and mechanism of action of LCN2 currently remain unclear. Methods The LCN2-overexpressing endometrial carcinoma cell lines, HHUA and RL95-2, and LCN2-low-expressing one, HEC1B, were used. The effects of LCN2 on cell migration, cell viability, and apoptosis under various stresses, including ultraviolet (UV) irradiation and cisplatin treatment, were examined using the scratch wound healing assay, WST-1 assay, and Apostrand assay, respectively. Results LCN2-silencing using shRNA method significantly reduced the migration ability of cells (p<0.05). Cytotoxic stresses significantly decreased the viability of LCN2-silenced cells more than that of control cells. In contrast, LCN2 overexpression was significantly increased cisplatin resistance. These effects were canceled by the addition of the iron chelator, deferoxamine. After UV irradiation, the expression of phosphorylated Akt (pAkt) was decreased in LCN2-silenced cells, and the PI3K inhibitor canceled the difference induced in UV sensitivity by LCN2. The cisplatin-induced expression of pAkt was not affected by LCN2; however, the expression of p53 and p21 was increased by LCN2-silencing. Conclusions These results indicated that LCN2 was involved in the migration and survival of endometrial carcinoma cells under various stresses in an iron-dependent manner. The survival function of LCN2 may be exerted through the PI3K pathway and suppression of the p53-p21 pathway. These functions of LCN2 may increase the malignant potential of endometrial carcinoma cells. PMID:27168162

  10. Endometrial cancer and antidepressants: A nationwide population-based study.

    PubMed

    Lin, Chiao-Fan; Chan, Hsiang-Lin; Hsieh, Yi-Hsuan; Liang, Hsin-Yi; Chiu, Wei-Che; Huang, Kuo-You; Lee, Yena; McIntyre, Roger S; Chen, Vincent Chin-Hung

    2016-07-01

    To our knowledge, the association between antidepressant exposure and endometrial cancer has not been previously explored. Herein, we aim to investigate the association between antidepressant prescription, including novel antidepressants, and the risk for endometrial cancer in a population-based study.Data for the analysis were derived from National Health Insurance Research Database. We identified 8392 cases with a diagnosis of endometrial cancer and 82,432 matched controls. A conditional logistic regression model was used, with adjusting for potentially confounding variables (e.g., comorbid psychiatric diseases, comorbid physical diseases, and other medications). Risk for endometrial cancer in the population-based study sample was categorized by, and assessed as a function of, antidepressant prescription and cumulative dosage.We report no association between endometrial cancer incidence and antidepressant prescription, including those prescribed either selective serotonin reuptake inhibitors (adjusted odds ratio [OR] = 0.98; 95% confidence interval [CI], 0.84-1.15) or serotonin norepinephrine reuptake inhibitors (adjusted OR = 1.14; 95% CI, 0.76-1.71). We also did not identify an association between higher cumulative doses of antidepressant prescription and endometrial cancer.There was no association between antidepressant prescription and endometrial cancer. PMID:27442640

  11. Regression of latent endometrial precancers by progestin infiltrated intrauterine device.

    PubMed

    Ørbo, Anne; Rise, Cecil E; Mutter, George L

    2006-06-01

    PTEN tumor suppressor inactivation is the earliest step in endometrial carcinogenesis, occurring in morphologically unremarkable endometrial glands in half of normal women. We test the hypothesis that sex hormones positively or negatively select for these "latent precancers" by examining their emergence, persistence, and regression rates under differing hormonal conditions. Perimenopausal and postmenopausal women had an intake endometrial biopsy and underwent hormonal therapy with progestin-impregnated intrauterine device (IUD; n = 21), cyclic oral progestins (n = 28), or surveillance only (n = 22) with follow-up biopsies. For comparison, premenopausal naturally cycling endometrial biopsies were studied as single time points in 87 patients and multiple surveillance time points in 34 patients. Biopsies in which any PTEN protein-null glands were found by immunohistochemistry were scored as containing a latent endometrial precancer. All groups had a similar proportion of latent precancers at intake but differed after therapy. Emergence rates were highest (21%) for the naturally cycling premenopausal group compared with just 9% for untreated perimenopausal women. The IUD group had the highest rate of regression, with a 62% pretherapy and 5% post-therapy rate of latent precancers. This contrasted to nonsignificant changes for the oral progestin and untreated control groups. Delivery of high doses of progestins locally to the endometrium by IUD leads to ablation of preexisting PTEN-inactivated endometrial latent precancers and is a possible mechanism for reduction of long-term endometrial cancer risk known to occur in response to this hormone.

  12. Regression of latent endometrial precancers by progestin infiltrated intrauterine device

    PubMed Central

    Ørbo, Anne; Rise, Cecil E.; Mutter, George L.

    2008-01-01

    PTEN tumor suppressor inactivation is the earliest step in endometrial carcinogenesis, occurring in morphologically unremarkable endometrial glands in half of normal women. We test the hypothesis that sex hormones positively or negatively select for these “latent precancers” by examining their emergence, persistence, and regression rates under differing hormonal conditions. Peri and postmenopausal women had an intake endometrial biopsy and underwent hormonal therapy with progestin-impregnated intrauterine device (“IUD”, n=21), cyclic oral progestins (n=28), or surveillance only (n=22), with followup biopsies. For comparison, premenopausal naturally cycling endometrial biopsies were studied as single timepoints in 87 patients, and multiple surveillance timepoints in 34. Biopsies in which any PTEN protein null glands were found by immunohistochemistry were scored as containing a latent endometrial precancer. All groups had a similar proportion of latent precancers at intake, but differed after therapy. Emergence rates were highest (21%) for the naturally cycling premenopausal group, in comparison to just 9% for untreated perimenopausal women. The IUD group had the highest rate of regression, with a 62% pre and 5% post therapy rate of latent precancers. This contrasted to non-significant changes for the oral progestin and untreated control groups. Delivery of high doses of progestins locally to the endometrium by IUD leads to ablation of pre-existing PTEN-inactivated endometrial latent precancers, and is a possible mechanism for reduction of long term endometrial cancer risk known to occur in response to this hormone. PMID:16740697

  13. [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.

  14. Expression of the ELAV-like protein HuR in the cytoplasm is associated with endometrial carcinoma progression.

    PubMed

    Wang, Dandan; Wang, Min; Hu, Chang'e; Shuang, Ting; Zhou, Yingying; Yan, Xiaoyu

    2014-12-01

    Human antigen R (HuR) is an mRNA-binding factor that belongs to the embryonic lethal abnormal vision/Hu protein family which may function as a tumor maintenance gene in a variety of carcinomas. However, there is no study to analyze HuR expression in endometrial carcinoma. Here, we investigated the expression of HuR in endometrial carcinoma carcinogenesis and subsequent progression. The expression of HuR and estrogen receptor alpha (ER-α) protein was examined by immunohistochemistry on paraffin embedding specimens containing endometrial carcinoma and adjacent non-cancerous tissues. Short hairpin RNA against HuR was transfected to investigate the role of HuR in regulating the expression of ER-α and progression in endometrial carcinoma. Cell viability and cycle were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry, respectively. Apoptosis was examined by annexin V apoptosis assay. Our study result show that cytoplasmic HuR expression is more frequent in poorly differentiated carcinomas (p = 0.005), advanced stage (p = 0.020), and positive ER-α expression (p = 0.026). Three HuR short hairpin RNAs (shRNAs) were transfected into Ishikawa cells, and we selected the most effective shRNA for the following experiments. After the transfection, the ER-α protein level was decreased. Further, decreased expression of HuR resulted in the inhibition of proliferation and induced apoptosis in Ishikawa cells. Our results showed that HuR could be a causal factor of ER-α regulation in Ishikawa cells and thus may induce the hormone-dependent endometrial carcinoma.

  15. 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.

  16. Water-extracted Perilla frutescens increases endometrial receptivity though leukemia inhibitory factor-dependent expression of integrins.

    PubMed

    Kim, Eun-Yeong; Choi, Hee-Jung; Chung, Tae-Wook; Choi, Jun-Yong; Kim, Hyung Sik; Jung, Yeon-Seop; Lee, Syng-Ook; Ha, Ki-Tae

    2016-08-01

    The leaves and stems of Perilla frutescens var. acuta Kudo (PF) have been used to prevent threatened abortion in traditional medicine in the East Asian countries. Because reduced receptivity of endometrium is a cause of abortion, we analyzed the action of PF on the endometrial receptivity. PF increased the level of leukemia inhibitory factor (LIF), a major cytokine regulating endometrial receptivity, and LIF receptor in human endometrial Ishikawa cells. The PF-induced LIF expression was mediated by c-jun N-terminal kinase (JNK) and p38 pathways. Adhesion between Ishikawa cells and trophoblastic JAr cells stimulated by PF treatment was abolished by knock down of LIF expression or antagonism of LIFR. In addition, the expressions of integrin β3 and β5 were increased by PF treatment in Ishikawa cells. The PF-induced expression of integrin β3 and β5 was reduced with an LIFR antagonist. Neutralization of both integrins successfully blocked PF-stimulated adhesion of JAr cells and Ishikawa cells. These results suggest that PF enhanced the adhesion between Ishikawa cells and JAr cells by increasing the expression of integrin β3 and β5 via an LIF-dependent pathway. Given the importance of endometrial receptivity in successful pregnancy, PF can be a novel and effective candidate for improving pregnancy rate. PMID:27562703

  17. 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

  18. Ethanol labeling: detection of early fluid absorption in endometrial resection.

    PubMed

    Duffy, S; Cruise, M; Reilly, C; Reid, P C; Sharp, F

    1992-02-01

    A study is presented of ethanol labeling of irrigation fluid in endometrial resection. The introduction of ethanol labeling and intraoperative breath ethanol analysis provided an inexpensive and potentially useful means of detecting early fluid absorption during uterine surgery. The breath ethanol analyzer used was a hand-held meter; the irrigant solution was 5% dextrose with 1% ethanol. Simultaneous breath and venous samples were taken from women undergoing endometrial resection. An increase in breath ethanol was positively correlated with fluid absorption, blood ethanol, and serum glucose. This technique may prove valuable in preventing fluid overload during endometrial resection.

  19. 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.

  20. 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 with the potential to i

  1. Monitoring of human endometrial function by radiommunoassay of PEP

    SciTech Connect

    Joshi, Sh. G.

    1984-12-18

    The present invention relates to a novel method for the quantitative determination of PEP (progestagen-associated endometrial protein) in a body fluid by radioimmunoassay. The technique is useful in monitoring the function of the human endometrium.

  2. 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.

  3. Effects of Bu-Shen-An-Tai recipe and its two components on endometrial morphology during peri-implantation in superovulated mice.

    PubMed

    Cui, Dan-Dan; Zheng, Cui-Hong; Gong, Ping; Wen, Lu; Ma, Wen-Wen; Zhou, Shun-Chang; Zhang, Ming-Min

    2014-10-01

    The aim of this study was to investigate the effect of Bu-Shen-An-Tai recipe (BSATR) and its two components (Bushen recipe, and Huoxue recipe) on endometrial morphology during peri-implantation in superovulated mice. Mice were randomly divided into five groups, including the normal (N), model (M), Bushen (BS), Huoxue (HX) and Bu-Shen-An-Tai (BH) groups. The uteri were collected on day 4 of pregnancy, and the endometrium thickness, microvessel density (MVD) and number of pinopodes observed. Compared with the M group, the endometrial thickness in the BS, HX and BH groups was significantly increased and there was a significant difference in endometrial thickness between the BS and the BH groups. The mean MVD was significantly lower in the M group than in the N group, and there was a significant increase in MVD in the BS, HX and BH groups as compared with the M group. Compared with the M group, the pinopode scores in the endometrium were significantly increased in the HX and BH groups; and the BS group had significantly higher pinipode scores than the HX and BH groups. In conclusion, the results of the present study demonstrated that the recipes (Bushen, Huoxue and BSATR) could improve the endometrial environment by regulating the endometrial thickness, MVD and the number of pinopodes at the window of implantation. Moreover, the Huoxue recipe and the BSATR were more efficient than the Bushen recipe, with the BSATR tending to have the most beneficial effects. PMID:25318891

  4. Progesterone Receptor Transcriptome and Cistrome in Decidualized Human Endometrial Stromal Cells

    PubMed Central

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

    2015-01-01

    Decidualization is a complex process involving cellular proliferation and differentiation of the endometrial stroma that is required to establish and support pregnancy. Progesterone acting via its nuclear receptor, the progesterone receptor (PGR), is a critical regulator of decidualization and is known to interact with certain members of the activator protein-1 (AP-1) family in the regulation of transcription. In this study, we identified the cistrome and transcriptome of PGR and identified the AP-1 factors FOSL2 and JUN to be regulated by PGR and important in the decidualization process. Direct targets of PGR were identified by integrating gene expression data from RNA sequencing with the whole-genome binding profile of PGR determined by chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) in primary human endometrial stromal cells exposed to 17β-estradiol, medroxyprogesterone acetate, and cAMP to promote in vitro decidualization. Ablation of FOSL2 and JUN attenuates the induction of 2 decidual marker genes, IGFBP1 and PRL. ChIP-seq analysis of genomic binding revealed that FOSL2 is bound in proximity to 8586 distinct genes, including nearly 80% of genes bound by PGR. A comprehensive assessment of the PGR-dependent decidual transcriptome integrated with the genomic binding of PGR identified FOSL2 as a potentially important transcriptional coregulator of PGR via direct interaction with regulatory regions of genes actively regulated during decidualization. PMID:25781565

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

    PubMed Central

    UMENE, KIYOKO; YANOKURA, MEGUMI; BANNO, KOUJI; IRIE, HARUKO; ADACHI, MASATAKA; IIDA, MIHO; NAKAMURA, KANAKO; NOGAMI, YUYA; MASUDA, KENTA; KOBAYASHI, YUSUKE; TOMINAGA, EIICHIRO; AOKI, DAISUKE

    2015-01-01

    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. PMID:25625960

  6. MiR-202 promotes endometriosis by regulating SOX6 expression

    PubMed Central

    Zhang, Dongli; Li, Yanyun; Tian, Jun; Zhang, Hongxia; Wang, Shelian

    2015-01-01

    Objectives: This study is to investigate the role and mechanism of microRNA-202 (miR-202) in endometriosis. Methods: Forty-five cases of ectopic endometrial tissues, 25 cases of eutopic endometrial tissues and 26 cases of normal endometrial tissues were collected. MiR-202 expression was detected by quantitative RT-PCR. The protein expressions of SOX6 (sex determining region Y-box 6) and its downstream proteins (p21, cyclin D1 and pRb (retinoblastoma protein)) were detected by immunochemistry and western blot. MTT and transwell assays were used to examine cell proliferation and cell migration. The dual luciferase assay was applied to validate whether miR-202 can directly target SOX6 gene. Results: MiR-202 was highly expressed in eutopic and ectopic endometrial tissues than normal endometrial tissues (P < 0.05), and the expression was higher in tissues with III/IV stages than I/II stages (P < 0.05). The expression of SOX6 protein was lower in ectopic endometrial tissues than in normal endometrial tissues. In ectopic endometrial tissues, the expression of p21 was decreased while cyclin D1 and pRb was up-regulated than in normal endometrial tissues (P < 0.05). In cultured endometrial cells, miR-202 down-regulation induced up-regulation of SOX6 and p21 whereas down-regulation of cyclin D1 and pRb. MiR-202 promoted the proliferation and metastasis of endometrial cells. And, miR-202 could complementary bind to SOX6 3’UTR to regulate the expression of SOX6. Conclusion: MiR-202 was up-regulated in the endometriosis. Through targeting SOX6 and its downstream proteins (p21, cyclin D1 and pRb), miR-202 can promote the progression of endometriosis. PMID:26770366

  7. 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…

  8. 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

  9. 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. PMID:26161798

  10. Effect of luteal-phase support on endometrial microRNA expression following controlled ovarian stimulation

    PubMed Central

    2012-01-01

    Background Studies suggested that microRNAs influence cellular activities in the uterus including cell differentiation and embryo implantation. In assisted reproduction cycles, luteal phase support, given to improve endometrial characteristics and to facilitate the implantation process, has been a standard practice. The effect of different types of luteal phase support using steroid hormones in relation to endometrial miRNA profiles during the peri-implantation period has not seen described. This study was designed to evaluate the expression of miRNAs during the luteal phase following controlled ovarian stimulation for IVF and the influence of different luteal phase support protocols on miRNA profiles. Methods The study was approved by the Johns Hopkins Hospital Institutional Review Board. Endometrial biopsies were obtained on the day of oocyte retrieval from 9 oocyte donors (group I). An additional endometrial biopsy was obtained 3–5 days later (Group II) after the donors were randomized into three groups. Group IIa had no luteal-phase support, group IIb had luteal support with micronized progesterone (P), and Group IIc had luteal support with progesterone plus 17-beta-estradiol (P + E). Total RNA was isolated and microarray analysis was performed using an Illumina miRNA expression panel. Results A total of 526 miRNAs were identified. Out of those, 216 miRNAs were differentially regulated (p < 0.05) between the comparison groups. As compared to the day of retrieval, 19, 11 and 6 miRNAs were differentially regulated more than 2 fold in the groups of no support, in the P support only, and in the P + E support respectively, 3–5 days after retrieval. During the peri-implantation period (3–5 days after retrieval) the expression of 33 and 6 miRNAs increased, while the expression of 3 and 0 miRNAs decreased, in the P alone and in the P + E group respectively as compared to the no steroid supplementation group. Conclusion Luteal support

  11. Lessons learnt from the Climate Dialogue initiative

    NASA Astrophysics Data System (ADS)

    Crok, Marcel; Strengers, Bart; Vasileiadou, Eleftheria

    2015-04-01

    The weblog Climate Dialogue (climatedialogue.org) has been an experimental climate change communication project. It was the result of a motion in the Dutch parliament, which asked the Dutch government "to also involve climate sceptics in future studies on climate change". Climate Dialogue was set up by the Royal Netherlands Meteorological Institute (KNMI), the Netherlands Environmental Assessment Agency (PBL), and Dutch science journalist Marcel Crok. It operated for slightly more than two years (From November 2012 till December 2014). Around 20 climate scientists from all over the world, many of them leading in their respective fields, participated in six dialogues. Climate Dialogue was a moderated blog on controversial climate science topics introducing a combination of several novel elements: a) bringing together scientists with widely separated viewpoints b) strict moderation of the discussion and c) compilation of executive and extended summaries of the discussions that were approved by the invited scientists. In our talk, we will discuss the operation and results of the Climate Dialogue project, focusing more explicitly on the lessons learnt with respect to online climate change communication addressing the question: "To what extent can online climate change communication bring together climate scientists with widely separated viewpoints, and what would be the advantage of such communication practice?" We identify how Climate Dialogue was received and perceived by the participating scientists, but also by different scientific and online communities. Finally, we present our ideas on how Climate Dialogue could evolve in a novel way of contributing to (climate) science and what steps would be necessary and/or beneficial for such a platform to survive and succeed.

  12. Teachers' Questions and Responses during Teacher-Student Feedback Dialogues

    ERIC Educational Resources Information Center

    Dekker-Groen, Agaath; Van der Schaaf, Marieke; Stokking, Karel

    2015-01-01

    In vocational education, students have to develop competences for reflection to self-regulate their development during their career. Students' reflection can be supported by teachers interacting with students and giving them prompts. In this study, 46 videotaped feedback dialogues of 23 teachers and their individual students were analysed. A…

  13. Efficacy of microwave ablation for the treatment of endometrial carcinoma: A report of 3 cases

    PubMed Central

    NAKAMURA, KOHEI; NAKAYAMA, KENTARO; ISHIKAWA, MASAKO; KATAGIRI, HIROSHI; ISHIBASHI, TOMOKA; SATO, EMI; AMANO, CHIKA; KYO, SATORU

    2016-01-01

    Microwave endometrial ablation (MEA) is effective for the emergency control of uterine hemorrhage. However, to the best of our knowledge, there has been only a single report of life-threatening hemorrhage induced by endometrial carcinoma that was treated with MEA. The present report evaluates the efficacy of MEA as an emergency therapeutic option for the control of bleeding due to advanced endometrial carcinoma and minimally-invasive, early-stage endometrial carcinoma in 3 patients. MEA was able to effectively control massive uterine bleeding due to endometrial carcinoma in 2 patients with advanced disease and was curative in a patient with minimally-invasive endometrial carcinoma. Given its safety, simplicity and effectiveness, MEA may be utilized for the emergency treatment of uterine bleeding in advanced endometrial carcinoma, and may be used as a curative treatment in early-stage endometrial carcinoma. PMID:27123057

  14. What Should You Ask Your Health Care Team About Endometrial Cancer?

    MedlinePlus

    ... endometrial cancer survivor What should you ask your health care team about endometrial cancer? As you cope with ... only ones who can give you information. Other health care professionals, such as nurses and social workers, can ...

  15. 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. PMID:24320648

  16. 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.

  17. Progesterone receptor gene variants and risk of endometrial cancer

    PubMed Central

    O'Mara, Tracy A.; Fahey, Paul; Ferguson, Kaltin; Marquart, Louise; Lambrechts, Diether; Despierre, Evelyn; Vergote, Ignace; Amant, Frederic; Hall, Per; Liu, Jianjun; Czene, Kamila; Rebbeck, Timothy R.; Ahmed, Shahana; Dunning, Alison M.; Gregory, Catherine S.; Shah, Mitul; Webb, Penelope M.; Spurdle, Amanda B.

    2011-01-01

    Prolonged excessive estrogen exposure unopposed by progesterone is widely accepted to be a risk factor for endometrial cancer development. The physiological function of progesterone is dependent upon the presence of its receptor [progesterone receptor (PGR)] and several studies have reported single nucleotide polymorphisms (SNPs) in the PGR gene to be associated with endometrial cancer risk. We sought to confirm the associations with endometrial cancer risk previously reported for four different PGR polymorphisms. A maximum of 2888 endometrial cancer cases and 4483 female control subjects from up to three studies were genotyped for four PGR polymorphisms (rs1042838, rs10895068, rs11224561 and rs471767). Logistic regression with adjustment for age, study, ethnicity and body mass index was performed to calculate odds ratios (ORs) and associated 95% confidence intervals (CIs) and P-values. Of the four SNPs investigated, only rs11224561 in the 3′ region of the PGR gene was found to be significantly associated with endometrial cancer risk. The A allele of the rs11224561 SNP was associated with increased risk of endometrial cancer (OR per allele 1.31; 95% CI 1.12–1.53, P = 0.001, adjusted for age and study), an effect of the same magnitude and direction as reported previously. We have validated the endometrial cancer risk association with a tagSNP in the 3′ untranslated region of PGR previously reported in an Asian population. Replication studies will be required to refine the risk estimate and to establish if this, or a correlated SNP, is the underlying causative variant. PMID:21148628

  18. Endometrial beta3 Integrin profile reflects endometrial receptivity defects in women with unexplained recurrent pregnancy loss

    PubMed Central

    2014-01-01

    Background The pathophysiology of recurrent pregnancy loss (RPL) is still unknown in 50% of the cases. Herein we measure the expression of beta3 integrin subunit, a well-known implantation marker, in women with or without RPL and correlate it with the histological dating of the endometrial tissue. Methods LH-timed endometrial biopsies were obtained from cases (RPL; n = 21, age 33.9+/-4.7) and healthy controls (n = 29; age 29.8+/-4.1) during the mid-secretory phase (post ovulatory day: 8 to 10). Endometrial samples were timed histologically according to Noyes’ criteria and underwent immunohistochemical staining for beta3 integrin expression. For statistical analysis the semi-quantitative HSCORE was assessed. Type I (beta3 negative in an out-of-phase endometrium) and Type II defect (beta3 negative in an in-phase endometrium) were also analysed. Statistical analysis was done with Student t-test, Mann Whitney U test, ANCOVA and chi square for trend. Significance was set as P < 0.05. Results The mean (SD) age in controls was lower compared to cases [(29.8 (4.1) vs. 33.9 (4.7) – P = 0.001; Student t-test)]. The median (range) expression of beta3 integrin in controls and cases was 1.94 (0 to 3.5) vs. 0.82 (0 to 3.6), respectively (P = 0.001; Mann Whitney U test). Significance was still significant after adjusting for age (P = 0.03;ANCOVA). The normal positive staining > =0.7 of beta3 integrin subunit and in-phase endometrium was seen in 24 out of 29 (82.8%) controls, but in only 6 out of 21 (28.6%) of cases with RPL; Type I and II defects were seen in 10.3 and 6.9% of controls, while present in 52.4 and 19.1% of cases, respectively (P = 0.0005; chi-square). Conclusions Women with unexplained RPL had significantly reduced integrin expression compared to controls. Our findings underline the need for further molecular analysis of endometrial tissue in affected women. PMID:24950982

  19. 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…

  20. 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…

  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. A Risk-Scoring Model for the Prediction of Endometrial Cancer among Symptomatic Postmenopausal Women with Endometrial Thickness > 4 mm

    PubMed Central

    Mfuta, Kabala; Setti, Tiziano; Cerami, Lillo Bruno; Bergamini, Ezio; Boselli, Fausto

    2014-01-01

    Objective. To develop and test a risk-scoring model for the prediction of endometrial cancer among symptomatic postmenopausal women at risk of intrauterine malignancy. Methods. We prospectively studied 624 postmenopausal women with vaginal bleeding and endometrial thickness > 4 mm undergoing diagnostic hysteroscopy. Patient characteristics and endometrial assessment of women with or without endometrial cancer were compared. Then, a risk-scoring model, including the best predictors of endometrial cancer, was tested. Univariate, multivariate, and ROC curve analysis were performed. Finally, a split-sampling internal validation was also performed. Results. The best predictors of endometrial cancer were recurrent vaginal bleeding (odds ratio (OR) = 2.96), the presence of hypertension (OR = 2.01) endometrial thickness > 8 mm (OR = 1.31), and age > 65 years (OR = 1.11). These variables were used to create a risk-scoring model (RHEA risk-model) for the prediction of intrauterine malignancy, with an area under the curve of 0.878 (95% CI 0.842 to 0.908; P < 0.0001). At the best cut-off value (score ≥ 4), sensitivity and specificity were 87.5% and 80.1%, respectively. Conclusion. Among symptomatic postmenopausal women with endometrial thickness > 4 mm, a risk-scoring model including patient characteristics and endometrial thickness showed a moderate diagnostic accuracy in discriminating women with or without endometrial cancer. Based on this model, a decision algorithm was developed for the management of such a population. PMID:24991535

  3. Oral Bisphosphonate Use and Risk of Postmenopausal Endometrial Cancer

    PubMed Central

    Newcomb, Polly A.; Passarelli, Michael N.; Phipps, Amanda I.; Anderson, Garnet L.; Wactawski-Wende, Jean; Ho, Gloria Y.F.; O'Sullivan, Mary Jo; Chlebowski, Rowan T.

    2015-01-01

    Purpose Bisphosphonates are common medications used for the treatment of osteoporosis and are also used to reduce metastases to bone in patients with cancer. Several studies, including the Women's Health Initiative (WHI), have found that use of bisphosphonates is associated with reduced risk of developing breast cancer, but less is known about associations with other common malignancies. This study was aimed at examining the effects of bisphosphonates on the risk of endometrial cancer. Methods We evaluated the relationship between use of oral bisphosphonates and endometrial cancer risk in a cohort of 89,918 postmenopausal women participating in the WHI. A detailed health interview was conducted at baseline, and bisphosphonate use was ascertained from an inventory of regularly used medications at baseline and over follow-up. All women had an intact uterus at the time of study entry. Results During a median follow-up of 12.5 years, 1,123 women were diagnosed with incident invasive endometrial cancer. Ever use of bisphosphonates was associated with reduced endometrial cancer risk (adjusted hazard ratio, 0.80; 95% CI, 0.64 to 1.00; P = .05), with no interactions observed with age, body mass index, or indication for use. Conclusion In this large prospective cohort of postmenopausal women, bisphosphonate use was associated with a statistically significant reduction in endometrial cancer risk. PMID:25713431

  4. Changes in global gene expression during in vitro decidualization of rat endometrial stromal cells

    PubMed Central

    Vallejo, Griselda; Maschi, Darío; Citrinovitz, Ana Cecilia Mestre; Aiba, Kazuhiro; Maronna, Ricardo; Yohai, Victor; Ko, Minoru S. H.; Beato, Miguel; Saragüeta, Patricia

    2009-01-01

    During the preimplantation phase of pregnancy the endometrial stroma differentiates into decidua, a process that implies numerous morphological changes and is an example of physiological transdifferentiation. Here we show that UIII rat endometrial stromal cells cultured in the presence of calf serum acquired morphological features of decidual cells and expressed decidual markers. To identify genes involved in decidualization we compared gene expression patterns of control and decidualized UIII cells using cDNA microarray. We found 322 annotated genes exhibiting significant differences in expression (>3 fold, FDR > 0.005), of which 312 have not been previously related to decidualization. Analysis of overrepresented functions revealed that protein synthesis, gene expression and chromatin architecture and remodeling are the most relevant modified functions during decidualization. Relevant genes are also found in the functional terms differentiation, cell proliferation, signal transduction, and matrix/structural proteins. Several of these new genes involved in decidualization (Csdc2, Trim27, Eef1a1, Bmp1, Wt1, Aes, Gna12, and Men1) are shown to be also regulated in uterine decidua during normal pregnancy. Thus, the UIII cell culture model will allow future mechanistic studies to define the transcriptional network regulating reprogramming of stromal cells into decidual cells. PMID:19780023

  5. 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

  6. Dialogue: A Theoretical Framework for Distance Education Instructional Systems

    ERIC Educational Resources Information Center

    Gorsky, Paul; Caspi, Avner

    2005-01-01

    This paper presents a theoretical framework for viewing elements that comprise distance education instructional systems in terms of dialogue. It is assumed that learning is mediated by intrapersonal dialogue and facilitated by interpersonal dialogue. Every resource in a distance education instructional system (eg, instructor availability,…

  7. 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.…

  8. 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…

  9. 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…

  10. Research Currents: Dialogue as the Heart of Learning.

    ERIC Educational Resources Information Center

    Shuy, Roger W.

    1987-01-01

    Discusses the importance of dialogue in learning, notes that it is lacking in many educational situations, and recommends the use of written dialogue journals as a means of communication between teachers and individual students. Points out the advantages of dialogue journals for improving writing for different social purposes. (SKC)

  11. Interreligious Dialogue in Schools: Beyond Asymmetry and Categorisation?

    ERIC Educational Resources Information Center

    Riitaoja, Anna-Leena; Dervin, Fred

    2014-01-01

    Interreligious dialogue is a central objective in European and UNESCO policy and research documents, in which educational institutions are seen as central places for dialogue. In this article, we discuss this type of dialogue under the conditions of asymmetry and categorisation in two Finnish schools. Finnish education has often been lauded for…

  12. 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…

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

    ClinicalTrials.gov

    2016-02-09

    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

  14. Educating Elites in Democratic Societies: A Dialogue

    ERIC Educational Resources Information Center

    Agassi, Joseph; Swartz, Ronald

    2007-01-01

    This dialogue centers on the following questions: (1) How can schools help a society select or identify new elites who are hopefully as good as and perhaps even better than those individuals who belong to the existing elite system?, and (2) How can we create learning situations that provide the most general learner with a broad basic education?…

  15. 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,…

  16. Professional Academic Development through Professional Journal Dialogue

    ERIC Educational Resources Information Center

    Ruth, Damian; Naidoo, Kogi

    2012-01-01

    This paper presents the cooperative analysis by a lecturer and an academic development practitioner of a reflective journal dialogue over the 12 weeks of teaching a postgraduate course. Through a retrospective analysis of the journal the present paper explores the following issues: the framing of an inquiry; the personal-professional nexus; and…

  17. 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…

  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. Moving beyond Social Exclusion through Dialogue

    ERIC Educational Resources Information Center

    Aubert, Adriana

    2011-01-01

    The Dialogic Inclusion Contract (DIC) makes it possible to build a dialogue between the international scientific community and the knowledge derived from the experiences of social agents. This article presents the theoretical underpinnings and the process of developing and implementing the DIC. A case study of a primary school in a disadvantaged…

  20. Reflection, dialogue, and the possibilities of space.

    PubMed

    Kumagai, Arno K; Naidu, Thirusha

    2015-03-01

    To educate physicians who are capable of delivering ethical, socially responsible, patient-centered care, there have been calls for identifying curricular space for reflection on the human and societal dimensions of medicine. These appeals, however, beg the question: What does it mean to devote space in an otherwise busy curriculum for these types of reflection? This Perspective is an attempt to understand the nature of this educational space in terms of its purpose, uses, dynamics, and limitations, and the underlying components that allow reflection and transformation to occur. Reflections on psychosocial themes often take the form of dialogues, which differ from the discussions commonly encountered in clinical settings because they require the engagement of the participants' whole selves--life experiences, backgrounds, personal values, beliefs, and perspectives--in the exchanges. Dialogues allow for the inclusion of affective and experiential dimensions in addition to intellectual/cognitive domains in learning, and for an emphasis on discovering new perspectives, insights, and questions instead of limiting participants solely to an instrumental search for solutions. Although these reflections may vary greatly in their form and settings, the reflective space requires three qualities: safety and confidentiality, an intentional designation of a time apart from the distractions of daily life for reflection and dialogue, and an awareness of the transitional nature--the liminality--of a critically important period of professional identity development. In this open space of reflection and dialogue, one's identity as a humanistic physician takes form. PMID:25426737

  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 Needs a Point and Purpose.

    ERIC Educational Resources Information Center

    Robinson, Viviane M. J.

    1995-01-01

    Examines the writings of Burbules and Young, two major educational theorists committed to promoting and understanding the practice of dialogue in educational contexts, focusing on Jurgen Habermas's theory of communicative action. Their works have shown the necessity for researchers to move across disciplinary boundaries and developing theories of…

  3. 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 expressed in their paper…

  4. 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…

  5. Online Learning Dialogues in Learning through Work

    ERIC Educational Resources Information Center

    Bosley, Sara; Young, David

    2006-01-01

    Purpose--The aim of this paper is to describe a study of online, asynchronous dialogues between tutors and nine work-based postgraduate learners on learning through work (LtW) programmes. Design/methodology/approach-- Adopting a constructivist perspective and using a qualitative approach, 670 messages were segmented into semantic units and…

  6. 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…

  7. Dialogue of Cultures: The Israeli Experience.

    ERIC Educational Resources Information Center

    Iram, Yaacov

    The future of the Israeli society, like the future of all democratic, multicultural societies, will be determined by the ability to maintain a meaningful dialogue among its diverse groups: Jews and Arabs, immigrants from diverse cultures and socio-economic strata. This paper presents and analyzes an educational program to promote understanding and…

  8. 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…

  9. 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…

  10. 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…

  11. Working Papers in Dialogue Modeling, Volume 2.

    ERIC Educational Resources Information Center

    Mann, William C.; And Others

    The technical working papers that comprise the two volumes of this document are related to the problem of creating a valid process model of human communication in dialogue. In Volume 2, the first paper concerns study methodology, and raises such issues as the choice between system-building and process-building, and the advantages of studying cases…

  12. "Conscientization," Dialogue and Collaborative Problem Based Learning

    ERIC Educational Resources Information Center

    Armitage, Andrew

    2013-01-01

    It has been argued that Paulo Freire's concept of conscientization, where critical awareness and engagement are central to a problem-posing pedagogy, provides the philosophical principles to underpin Problem Based Learning (PBL). By using dialogue groups and a combination of learning strategies to discover the nature of a problem, understand its…

  13. A Dialogue between an Educator and Psychologist

    ERIC Educational Resources Information Center

    Noam, Gil G.; Bernstein-Yamashiro, Beth

    2013-01-01

    This conclusion to the volume presents a dialogue from the perspective of educator and clinician. With examples from professional development and practice, the discussion revolves around teacher training and the role of the administrator in creating a bounded and safe environment in which teachers can develop healthy relationships. It discusses…

  14. Age at Last Birth in Relation to Risk of Endometrial Cancer: Pooled Analysis in the Epidemiology of Endometrial Cancer Consortium

    PubMed Central

    Setiawan, Veronica Wendy; Pike, Malcolm C.; Karageorgi, Stalo; Deming, Sandra L.; Anderson, Kristin; Bernstein, Leslie; Brinton, Louise A.; Cai, Hui; Cerhan, James R.; Cozen, Wendy; Chen, Chu; Doherty, Jennifer; Freudenheim, Jo L.; Goodman, Marc T.; Hankinson, Susan E.; Lacey, James V.; Liang, Xiaolin; Lissowska, Jolanta; Lu, Lingeng; Lurie, Galina; Mack, Thomas; Matsuno, Rayna K.; McCann, Susan; Moysich, Kirsten B.; Olson, Sara H.; Rastogi, Radhai; Rebbeck, Timothy R.; Risch, Harvey; Robien, Kim; Schairer, Catherine; Shu, Xiao-Ou; Spurdle, Amanda B.; Strom, Brian L.; Thompson, Pamela J.; Ursin, Giske; Webb, Penelope M.; Weiss, Noel S.; Wentzensen, Nicolas; Xiang, Yong-Bing; Yang, Hannah P.; Yu, Herbert; Horn-Ross, Pamela L.; De Vivo, Immaculata

    2012-01-01

    Childbearing at an older age has been associated with a lower risk of endometrial cancer, but whether the association is independent of the number of births or other factors remains unclear. Individual-level data from 4 cohort and 13 case-control studies in the Epidemiology of Endometrial Cancer Consortium were pooled. A total of 8,671 cases of endometrial cancer and 16,562 controls were included in the analysis. After adjustment for known risk factors, endometrial cancer risk declined with increasing age at last birth (Ptrend < 0.0001). The pooled odds ratio per 5-year increase in age at last birth was 0.87 (95% confidence interval: 0.85, 0.90). Women who last gave birth at 40 years of age or older had a 44% decreased risk compared with women who had their last birth under the age of 25 years (95% confidence interval: 47, 66). The protective association was similar across the different age-at-diagnosis groups and for the 2 major tumor histologic subtypes (type I and type II). No effect modification was observed by body mass index, parity, or exogenous hormone use. In this large pooled analysis, late age at last birth was independently associated with a reduced risk of endometrial cancer, and the reduced risk persisted for many years. PMID:22831825

  15. 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…

  16. 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

  17. 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

  18. The Equine Endometrial Cup Reaction: A Fetomaternal Signal of Significance

    PubMed Central

    Antczak, D. F.; de Mestre, Amanda M.; Wilsher, Sandra; Allen, W. R.

    2015-01-01

    A remarkable feature of equine pregnancy is the development of the invasive trophoblast of the chorionic girdle and its formation of the gonadotrophin-secreting endometrial cup cells in early gestation. The details of this process have been revealed only slowly over the past century, since the first description of the endometrial cups in 1912. This centennial presents an opportunity to review the characteristics of the cells and molecules involved in this early, critical phase of placentation in the mare. The invasiveness of the chorionic girdle trophoblast appears to represent an atavistic attribute more commonly associated with the hemochorial placentae of primates and rodents but not with the more recently derived epitheliochorial placentae of the odd-toed ungulates. The nature of and raison d’etre for the strong fetal signals transmitted to the mare by the endometrial cup reaction, and her responses to these messages, are the subject of the present review. PMID:25387026

  19. 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.

  20. Endometrial abnormality in women with polycystic ovary syndrome.

    PubMed

    Shang, Kewei; Jia, Xiao; Qiao, Jie; Kang, Jihong; Guan, Youfei

    2012-07-01

    Polycystic ovary syndrome (PCOS) is the most common endocrinopathy associated with infertility and metabolic disorder in women of reproductive age. Although the clinical and biochemical features are heterogeneous with individuals, the most widely accepted clinical characteristics of PCOS are oligo- or anovulation combined with hyperandrogenism. With the higher rate of implantation failure after induction of ovulation or higher risk of spontaneous miscarriage after pregnancy, the reduced fertility is apparently attributed not only to anovulation but also to endometrial dysfunction in patients with PCOS. Here we review the features of the endometrial abnormalities in women with PCOS. The ability to improve the endometrial functions is of potential therapeutic targets to increase reproductive outcome of women with PCOS.

  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 polyp in an African wild dog (Lycaon pictus).

    PubMed

    Cho, H S; Park, N Y

    2006-11-01

    An 8-year-old female African wild dog (Lycaon pictus) from a zoo in Gyeonggi province, Republic of Korea presented with a 3.0 x 2.0 x 2.5 cm in size, smooth-surfaced, solitary pedunculated mass protruding into the uterine lumen. Microscopically, the mass was covered with epithelium, contained endometrial gland tissue, and was dilated in the vascularised stroma. Within the mass, there was extensive diffuse haemorrhage with several blood vessels apparently plugged with fibrin. At the base of the mass, the spaces lined with epithelium near the attachment of the stalk were interpreted to be glandular structures. There were segments of cuboidal epithelium found on the surface of the mass, which was similar to the lining the uterus. A diagnosis of an endometrial polyp was made based on the gross and histology findings. This is the first case report of a spontaneous endometrial polyp in an African wild dog.

  3. Cyclooxygenase-2 and p53 expressions in endometrial cancer.

    PubMed

    Jeon, Yong-Tark; Kang, Sokbom; Kang, Dae-Hee; Yoo, Keun-Young; Park, In-Ae; Bang, Yung-Jue; Kim, Jae Weon; Park, Noh-Hyun; Kang, Soon-Beom; Lee, Hyo-Pyo; Song, Yong-Sang

    2004-09-01

    Cyclooxygenase-2 (COX-2) has been known to be related with various types of carcinoma, but we have insufficient knowledge about the association between COX-2 and endometrial cancer. Many have reported a close relationship between p53 expression and a poor prognosis in endometrial cancer, but it is unclear whether p53 is an independent prognostic factor. To clarify these uncertainties, we examined the expressions of COX-2 and p53 in endometrial cancer tissues. The study was carried on 152 endometrial cancer patients who had operation at Seoul National University Hospital. Paraffin-embedded tissue blocks were sectioned and immunostained using monoclonal anti-COX-2 and anti-p53 antibodies. Twenty-seven (17.8%) specimens stained as COX-2 positive. COX-2 positivity was more frequently observed in postmenopausal patients than in premenopausal patients (8.8% versus 25.0%; P = 0.009). However, COX-2 positivity did not show a statistically significant association with any other clinicopathologic characteristic (parity, body mass index, histotype, International Federation of Gynecology and Obstetrics stage, grade, lymph node metastasis, deep myometrial invasion, or p53 overexpression). Thirty-one (20.4%) specimens showed p53 overexpression and this was significantly correlated with an advanced stage (P = 0.001), poor differentiation (P < 0.001), lymph node metastasis (P = 0.012), and deep myometrial invasion (P < 0.001). Multivariate Cox regression analysis showed that advanced stage was an independent prognostic factor of survival, but p53 overexpression was not. COX-2 may be associated with endometrial cancer carcinogenesis during the postmenopausal period but not with tumor aggressiveness and p53 overexpression. The p53 overexpression was found to be strongly associated with endometrial cancer aggressiveness.

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

    PubMed

    Lie, Geoffrey; Morley, Thomas; Chowdhury, Muhammad

    2016-01-01

    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.

  5. [Endometrial ossification: a report of four cases and literature review].

    PubMed

    Nevarez Bernal, Roberto; Vilchis Nava, Pablo; Kably Ambe, Alberto

    2007-03-01

    Endometrial ossification is a rare endometrial pathology. Its predisposing factors include history of uterine curettage to metabolic abnormalities. It usually presents in patients with secondary infertility and history of first trimester pregnancy loss, accompanied by severe dysmenorrhea and dyspareunia. The diagnosis is suspected by OB-GYN history and USG findings, therapeutic strategies range from D&C to hysterectomy, we propose diagnosis and management by hysteroscopy in order to preserve future fertility and minimize uterine damage. A review of four cases during 1985-2004 from a large assisted reproduction center in Mexico City is presented.

  6. 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.

  7. Evaluation of Metachronous Breast and Endometrial Cancers

    PubMed Central

    Grzankowski, Kassondra S.; Szender, J. Brian; Spring-Robinson, Chandra L.; Lele, Shashikant B.; Odunsi, Kunle O.; Frederick, Peter J.

    2016-01-01

    Background The time interval between diagnoses of breast cancer (BC) and endometrial cancer (EC) is not well established in women with metachronous primary tumors. We sought to examine this interval and identify associations with treatment-related and clinicopathologic factors. Methods We identified 141 patients who developed both cancers during 1966 to 2013. Patients were divided into 2 groups: group 1, BC first, and group 2, EC first. Subanalysis performed of group 1 (59 patients) stratified around adjuvant tamoxifen use: pre-1990 BC diagnosis and post. Results Fifty-nine and 82 patients were in groups 1 and 2, respectively. The mean time interval was comparable (76 vs 74 months, P = 0.861). Subanalysis divided group 1 into pre- (n = 27) and post- (n = 32) 1990 and resulted in different mean time intervals between diagnosis of metachronous cancers (106 vs 50 months, respectively [P = 0.042]). Median progression-free survival (PFS) and overall survival (OS) for EC were longer in the pre group (PFS, 51 vs 26 months [P = 0.169]; OS, 59 vs 27 months [P = 0.190]). Median PFS and OS for BC were also longer in this group (PFS, 147 vs 109 months [P = 0.005]; OS, 166 vs 114 months [P < 0.001]). Conclusions Our data indicate the mean time interval between the diagnosis of EC and BC was approximately 6 years. Disease-specific EC survival was worse for patients with a previous diagnosis of BC. Stratification around implementation of tamoxifen use shows comparable grade and stage but different time interval and survival, suggesting resulting effects from adjuvant therapy for BC. These results are useful in counseling women at risk. PMID:27648713

  8. Metformin Use and Endometrial Cancer Survival

    PubMed Central

    Nevadunsky, Nicole S.; Van Arsdale, Anne; Strickler, Howard D.; Moadel, Alyson; Kaur, Gurpreet; Frimer, Marina; Conroy, Erin; Goldberg, Gary L.; Einstein, Mark H.

    2013-01-01

    Objective Impaired glucose tolerance and diabetes are risk factors for the development of uterine cancer. Although greater progression free survival among diabetic patients with ovarian and breast cancer using metformin have been reported, no studies have assessed the association of metformin use with survival in women with endometrial cancer (EC). Methods We conducted a single-institution retrospective cohort study of all patients treated for uterine cancer from January 1999 through December 2009. Demographic, medical, social, and survival data were abstracted from medical records and the national death registry. Overall survival (OS) was estimated using Kaplan-Meier methods. Cox models were utilized for multivariate analysis. All statistical tests were two-sided. Results Of 985 patients, 114 (12%) had diabetes and were treated with metformin, 136 (14%) were diabetic but did not use metformin, and 735 (74%) had not been diagnosed with diabetes. Greater OS was observed in diabetics with non-endometrioid EC who used metformin than in diabetic cases not using metformin and non-endometrioid EC cases without diabetes (log rank test (p=0.02)). This association remained significant (hazard ratio = 0.54, 95% CI: 0.30–0.97, p<0.04) after adjusting for age, clinical stage, grade, chemotherapy treatment, radiation treatment and presence of hyperlipidemia in multivariate analysis. No association between metformin use and OS in diabetics with endometrioid histology was observed. Conclusion Diabetic EC patients with non-endometrioid tumors who used metformin had lower risk of death than women with EC who did not use metformin. These data suggest that metformin might be useful as adjuvant therapy for non-endometrioid EC. PMID:24189334

  9. Enhanced cyclooxygenase-2 expression levels and metalloproteinase 2 and 9 activation by Hexachlorobenzene in human endometrial stromal cells.

    PubMed

    Chiappini, Florencia; Bastón, Juan Ignacio; Vaccarezza, Agustina; Singla, José Javier; Pontillo, Carolina; Miret, Noelia; Farina, Mariana; Meresman, Gabriela; Randi, Andrea

    2016-06-01

    Hexachlorobenzene (HCB) is an organochlorine pesticide that induces toxic reproductive effects in laboratory animals. It is a dioxin-like compound and a weak ligand of the aryl hydrocarbon receptor (AhR). Endometriosis is characterized by the presence of functional endometrial tissues outside the uterine cavity. Experimental studies indicate that exposure to organochlorines can interfere with both hormonal regulation and immune function to promote endometriosis. Altered expression of metalloproteinases (MMPs) in patients with endometriosis, suggests that MMPs may play a critical role. In the endometriotic lesions, prostaglandin E2 (PGE2) produced by cyclooxygenase-2 (COX-2), binds to its EP4 receptor (EP4), and via c-Src kinase induces MMPs activation, promoting endometriosis. We examined the HCB action on MMP-2 and MMP-9 activities and expression, COX-2 levels, PGE2 signaling, and the AhR involvement in HCB-induced effects. We have used different in vitro models: (1) human endometrial stromal cell line T-HESC, (2) primary cultures of Human Uterine Fibroblast (HUF), and (3) primary cultures of endometrial stromal cells from eutopic endometrium of control (CESC) and subjects with endometriosis (EESC). Our results show that HCB enhances MMP-2 and MMP-9 activities in T-HESC, HUF and ESC cells. The MMP-9 levels were elevated in all models, while the MMP-2 expression only increased in ESC cells. HCB enhanced COX-2 and EP4 expression, PGE2 secretion and the c-Src kinase activation in T-HESC. Besides, we observed that AhR is implicated in these HCB-induced effects. In conclusion, our results show that HCB exposure could contribute to endometriosis development, affecting inflammation and invasion parameters of human endometrial cells. PMID:27038655

  10. 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

  11. Visual gene-network analysis reveals the cancer gene co-expression in human endometrial cancer

    PubMed Central

    2014-01-01

    Background Endometrial cancers (ECs) are the most common form of gynecologic malignancy. Recent studies have reported that ECs reveal distinct markers for molecular pathogenesis, which in turn is linked to the various histological types of ECs. To understand further the molecular events contributing to ECs and endometrial tumorigenesis in general, a more precise identification of cancer-associated molecules and signaling networks would be useful for the detection and monitoring of malignancy, improving clinical cancer therapy, and personalization of treatments. Results ECs-specific gene co-expression networks were constructed by differential expression analysis and weighted gene co-expression network analysis (WGCNA). Important pathways and putative cancer hub genes contribution to tumorigenesis of ECs were identified. An elastic-net regularized classification model was built using the cancer hub gene signatures to predict the phenotypic characteristics of ECs. The 19 cancer hub gene signatures had high predictive power to distinguish among three key principal features of ECs: grade, type, and stage. Intriguingly, these hub gene networks seem to contribute to ECs progression and malignancy via cell-cycle regulation, antigen processing and the citric acid (TCA) cycle. Conclusions The results of this study provide a powerful biomarker discovery platform to better understand the progression of ECs and to uncover potential therapeutic targets in the treatment of ECs. This information might lead to improved monitoring of ECs and resulting improvement of treatment of ECs, the 4th most common of cancer in women. PMID:24758163

  12. Androgen responsiveness of the new human endometrial cancer cell line MFE-296.

    PubMed

    Hackenberg, R; Beck, S; Filmer, A; Hushmand Nia, A; Kunzmann, R; Koch, M; Slater, E P; Schulz, K D

    1994-04-01

    MFE-296 endometrial cancer cells express androgen receptors in vitro. These cells, which are tumorigenic in nude mice, are derived from a moderately differentiated human endometrial adenocarcinoma. They express vimentin and the cytokeratins 7, 8, 18, and 19. Karyotyping revealed near-tetraploidy for most of the cells. No marker chromosomes were observed. DNA analyses confirmed the genetic identity of the cell line and the patient from whom the cell line was derived. Proliferation of MFE-296 cells was inhibited by the progestin R5020 and the androgen dihydrotestosterone (DHT). The inhibition of proliferation by DHT was antagonized by the antiandrogen Casodex, demonstrating the involvement of the androgen receptor. Androgen binding was determined at 22,000 binding sites per cell using a whole-cell assay (KD = 0.05 nM) and 30 fmol/mg protein with the dextran charcoal method; 7 fmol/mg protein of progesterone receptors were found, whereas estrogen receptors were below 5 fmol/mg protein. The androgen receptor was functionally intact, as demonstrated by transfection experiments with a reporter-gene construct, containing an androgen-responsive element. In MFE-296 cells the content of the androgen receptor was up-regulated by its own ligand.

  13. Natural Selection of Human Embryos: Decidualizing Endometrial Stromal Cells Serve as Sensors of Embryo Quality upon Implantation

    PubMed Central

    Teklenburg, Gijs; Salker, Madhuri; Molokhia, Mariam; Lavery, Stuart; Trew, Geoffrey; Aojanepong, Tepchongchit; Mardon, Helen J.; Lokugamage, Amali U.; Rai, Raj; Landles, Christian; Roelen, Bernard A. J.; Quenby, Siobhan; Kuijk, Ewart W.; Kavelaars, Annemieke; Heijnen, Cobi J.; Regan, Lesley; Brosens, Jan J.; Macklon, Nick S.

    2010-01-01

    Background Pregnancy is widely viewed as dependent upon an intimate dialogue, mediated by locally secreted factors between a developmentally competent embryo and a receptive endometrium. Reproductive success in humans is however limited, largely because of the high prevalence of chromosomally abnormal preimplantation embryos. Moreover, the transient period of endometrial receptivity in humans uniquely coincides with differentiation of endometrial stromal cells (ESCs) into highly specialized decidual cells, which in the absence of pregnancy invariably triggers menstruation. The role of cyclic decidualization of the endometrium in the implantation process and the nature of the decidual cytokines and growth factors that mediate the crosstalk with the embryo are unknown. Methodology/Principal Findings We employed a human co-culture model, consisting of decidualizing ESCs and single hatched blastocysts, to identify the soluble factors involved in implantation. Over the 3-day co-culture period, approximately 75% of embryos arrested whereas the remainder showed normal development. The levels of 14 implantation factors secreted by the stromal cells were determined by multiplex immunoassay. Surprisingly, the presence of a developing embryo had no significant effect on decidual secretions, apart from a modest reduction in IL-5 levels. In contrast, arresting embryos triggered a strong response, characterized by selective inhibition of IL-1β, -6, -10, -17, -18, eotaxin, and HB-EGF secretion. Co-cultures were repeated with undifferentiated ESCs but none of the secreted cytokines were affected by the presence of a developing or arresting embryo. Conclusions Human ESCs become biosensors of embryo quality upon differentiation into decidual cells. In view of the high incidence of gross chromosomal errors in human preimplantation embryos, cyclic decidualization followed by menstrual shedding may represent a mechanism of natural embryo selection that limits maternal investment in

  14. 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

  15. Empowering dialogues--the patients' perspective.

    PubMed

    Tveiten, Sidsel; Knutsen, Ingrid Ruud

    2011-06-01

    The aim of the study was to highlight the patients' experiences and perspectives of the dialogue with the health professionals at a pain clinic. This knowledge can develop and give nuanced understanding of patient empowerment and sense of control. Qualitative content analysis was used to reveal the meaning of the patients' experiences and perspectives during focus group interviews. The findings and interpretations revealed the main theme; preconditions and opportunities for participation. The main theme was represented by four subthemes; means for common understanding, basis for collaboration, acknowledgement and legitimacy. The findings and interpretations are discussed in the light of an evolving theory on women's sense of control while experiencing chronic pain and empowerment. The dialogue is very important related to aspects of control, remoralization and demoralization and is affected by external structural factors. This underlines the importance of further research focusing on empowerment and power.

  16. 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.

  17. Ethmoid metastasis of endometrial carcinoma causing mucocoele of maxillary antrum.

    PubMed

    Scott, A; Raine, M; Stansbie, J M

    1998-03-01

    We report a case of an antral mucocoele secondary to the obstruction of its ostium by metastatic endometrial carcinoma. This is the first report of such a cause for a mucocoele, and for a metastasis from such a tumour in the head and neck.

  18. Predictors of limph node metastasis in endometrial cancer

    PubMed Central

    IGNAT, FLORIN LAURENTIU; IRIMIE, ALEXANDRU; COSTIN, NICOLAE; ACHIMAS-CADARIU, PATRICIU; LISENCU, IOAN COSMIN

    2013-01-01

    Introduction Endometrial cancer is the most common gynecologic malignancy in developed countries. The adequate surgical staging proposed by FIGO (International Federation for Gynaecology and Obstetrics) advocates lymphadenectomy; however, it does not establish the indications, the type and the extent of lymphadenectomy, thus generating multiple controversies. Methods Retrospective, analytical study of patients treated surgically for endometrial adenocarcinoma in the Oncological Institute ”Prof. Dr. Ion Chiricuţă” Cluj-Napoca (IOCN) between January 2008 and December 2012 – 709 cases eligible for the study. Results 206 pelvic and/or paraaortic lymphadenectomies were performed, the average number of excised lymph nodes being 15.6. Overall in 4.4% of patients the lymph nodes were affected by metastases. The presence of each risk factor analysed was statistically significantly associated with lymph node metastasis (p<0.05). Age above 55 years was statistically significantly associated (p<0.05) with the presence of negative prognostic factors in the study. Conclusions The analysed histopathological and clinical prognostic factors were statistically significantly associated with lymphatic dissemination in endometrial cancer. We recommend treating endometrial cancer in tertiary centres by surgeons or gynaecologists-oncologists with experience in extensive peritoneal and retroperitoneal surgery. PMID:26527979

  19. JAZF1/SUZ12 gene fusion in endometrial stromal sarcomas.

    PubMed

    Hrzenjak, Andelko

    2016-01-01

    Endometrial stromal sarcomas (ESSs) belong to the rarest uterine malignancies (prevalence category <1-9/1,000,000). According to the new 2014 World Health Organisation (WHO) classification, they are separated into four categories; benign endometrial stromal nodules (ESNs), low grade endometrial stromal sarcomas (LG-ESSs), high-grade endometrial stromal sarcomas (HG-ESSs) and undifferentiated uterine sarcomas (UUSs). Due to heterogeneous histopathologic appearance these tumors still represent diagnostic challenge, even for experienced pathologists. ESSs are genetically very heterogeneous and several chromosomal translocations and gene fusions have so far been identified in these malignancies. To date the JAZF1/SUZ12 gene fusion is by far the most frequent and seems to be the cytogenetic hallmark of ESN and LG-ESS. Based on present literature data this gene fusion is present in approximately 75% of ESN, 50% of LG-ESS and 15% of HG-ESS cases. The frequency of JAZF1/SUZ12 appearance varies between classic ESS and different morphologic variants. This gene fusion is suggested to become a specific diagnostic tool, especially in difficult borderline cases. In combination with the recently described YWHAE/FAM22 gene fusion the JAZF1/SUZ12 fusion could be used to differentiate between LG-ESS and HG-ESS. The purpose of this review is to summarize literature data published in last two and a half decades about this gene fusion, as a contribution to our understanding of ESS genetics and pathogenesis. PMID:26879382

  20. Small non-coding RNA deregulation in endometrial carcinogenesis.

    PubMed

    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

    2015-03-10

    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

  1. 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

  2. Primary pulmonary carcinoid tumor with metastasis to endometrial polyp

    PubMed Central

    Momeni, Mazdak; Kolev, Valentin; Costin, Dan; Mizrachi, Howard H.; Chuang, Linus; Warner, Richard R.P.; Gretz, Herbert F.

    2012-01-01

    INTRODUCTION A carcinoid tumor occurring in the endometrium has been documented in the literature, but there is no report in regard to carcinoid tumor metastasis to endometrium. PRESENTATION OF CASE We report a case of a malignant carcinoid metastasis to an endometrial polyp. Patient underwent hysteroscopy, and polypectomy. The pathology demonstrated an endometrial polyp containing a 4 mm x 5 mm nodule of metastatic carcinoid tumor, consistent with metastasis from patient's known pulmonary carcinoid. The tumor was morphologically similar to the tumors of the right lung, with similar immune-profile. DISCUSSION This patient presented with a suspicious pelvic ultrasound. Due to her age, the first priority was to exclude uterine cancer. The endometrial polyp, which was found, had a small focus of metastatic carcinoid tumor. To the best of our knowledge, this finding has not been previously recorded in the literature. Our patient also had a history of metastatic carcinoid tumor to breast. This finding is also very uncommon. CONCLUSION This is the first case in the literature described a malignant carcinoid metastasis to an endometrial polyp. PMID:23127865

  3. Shadow cell differentiation from squamoid morule in endometrial adenoacanthoma.

    PubMed

    Nakamura, Toshitsugu

    2015-01-01

    Shadow cell differentiation (SCD), commonly found in cutaneous pilomatricoma (PMX), has been said to be extremely rare in extracutaneous tumors and its morphogenesis has not been clarified yet. In the present study, 25 cases of endometrial adenoacanthoma were examined with special reference to SCD and with immunohistochemistry for beta-catenin and CD10. Shadow cell nests (SCNs) were observed in 2 out of 5 cases of adenocarcinoma with squamoid morules and all of 4 cases of adenocarcinoma with squamous differentiation and morules, but not in any cases of adenocarcinoma with squamous differentiation. SCNs were just adjacent to morules with or without a mutual transition. Immunohistochemical examination revealed nuclear accumulation of beta-catenin and expression of CD10 in the squamoid morules around SCNs. These results indicate that SCNs are derived from squamoid morules in endometrial adenoacanthoma, and established a link between matrical basaloid cells in PMX and squamoid morules in endometrial adenoacanthoma, as common original tissues, showing nuclear accumulation of beta-catenin and expression of CD10, of SCNs. It seems that SCD is not so uncommon as previously estimated in endometrial adenoacanthoma.

  4. Synchronous Endometrial and Ovarian Carcinomas: Evidence of Clonality.

    PubMed

    Anglesio, Michael S; Wang, Yi Kan; Maassen, Madlen; Horlings, Hugo M; Bashashati, Ali; Senz, Janine; Mackenzie, Robertson; Grewal, Diljot S; Li-Chang, Hector; Karnezis, Anthony N; Sheffield, Brandon S; McConechy, Melissa K; Kommoss, Friedrich; Taran, Florin A; Staebler, Annette; Shah, Sohrab P; Wallwiener, Diethelm; Brucker, Sara; Gilks, C Blake; Kommoss, Stefan; Huntsman, David G

    2016-06-01

    Many women with ovarian endometrioid carcinoma present with concurrent endometrial carcinoma. Organ-confined and low-grade synchronous endometrial and ovarian tumors (SEOs) clinically behave as independent primary tumors rather than a single advanced-stage carcinoma. We used 18 SEOs to investigate the ancestral relationship between the endometrial and ovarian components. Based on both targeted and exome sequencing, 17 of 18 patient cases of simultaneous cancer of the endometrium and ovary from our series showed evidence of a clonal relationship, ie, primary tumor and metastasis. Eleven patient cases fulfilled clinicopathological criteria that would lead to classification as independent endometrial and ovarian primary carcinomas, including being of FIGO stage T1a/1A, with organ-restricted growth and without surface involvement; 10 of 11 of these cases showed evidence of clonality. Our observations suggest that the disseminating cells amongst SEOs are restricted to physically accessible and microenvironment-compatible sites yet remain indolent, without the capacity for further dissemination. PMID:26832771

  5. Common mitochondrial polymorphisms as risk factor for endometrial cancer

    PubMed Central

    Czarnecka, Anna M; Klemba, Aleksandra; Semczuk, Andrzej; Plak, Katarzyna; Marzec, Barbara; Krawczyk, Tomasz; Kofler, Barbara; Golik, Pawel; Bartnik, Ewa

    2009-01-01

    Endometrial carcinoma is the most commonly diagnosed gynaecological cancer in developed countries. Although the molecular genetics of this disease has been in the focus of many research laboratories for the last 20 years, relevant prognostic and diagnostic markers are still missing. At the same time mitochondrial DNA mutations have been reported in many types of cancer during the last two decades. It is therefore very likely that the mitochondrial genotype is one of the cancer susceptibility factors. To investigate the presence of mtDNA somatic mutations and distribution of inherited polymorphisms in endometrial adenocarcinoma patients we analyzed the D-loop sequence of cancer samples and their corresponding normal tissues and moreover performed mitochondrial haplogroup analysis. We detected 2 somatic mutation and increased incidence of mtDNA polymorphisms, in particular 16223C (80% patients, p = 0.005), 16126C (23%, p = 0.025) and 207A (19%, p = 0.027). Subsequent statistical analysis revealed that endometrial carcinoma population haplogroup distribution differs from the Polish population and that haplogroup H (with its defining polymorphism - C7028T) is strongly underrepresented (p = 0.003), therefore might be a cancer-protective factor. Our report supports the notion that mtDNA polymorphisms establish a specific genetic background for endometrial adenocarcinoma development and that mtDNA analysis may result in the development of new molecular tool for cancer detection. PMID:19863780

  6. 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.

  7. Controlled quantum dialogue robust against conspiring users

    NASA Astrophysics Data System (ADS)

    Kao, Shih-Hung; Hwang, Tzonelih

    2016-07-01

    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. Squamous morules are functionally inert elements of premalignant endometrial neoplasia.

    PubMed

    Lin, Ming-Chieh; Lomo, Lesley; Baak, Jan P A; Eng, Charis; Ince, Tan A; Crum, Christopher P; Mutter, George L

    2009-02-01

    Squamous morules are a common component of premalignant glandular lesions that are followed by glandular, rather than squamous, carcinomas. We tested the hypothesis that the appearance of glands associated with morules predicts cancer risk, and undertook molecular testing to determine the clonal and hormonal response properties of admixed squamous and glandular elements. A total of 66 patients with squamous morules in an index endometrial biopsy had follow-up clinical data (average follow-up: interval 31 months, 2.5 biopsies) showing development of carcinoma in 11% (7/66) of cases. The histological appearance of morule-associated glands in the index biopsy was significantly associated with this clinical outcome, with the majority (71%, 5/7) of cancer occurrences following an overtly premalignant lesion (endometrial intraepithelial neoplasia) with squamous morules. Eight endometrial intraepithelial neoplasias with squamous morules were examined by immunohistochemistry for estrogen and progesterone receptors and mitotic activity (Ki-67 antigen percent stained). Glandular components had abundant estrogen and progesterone receptors, and high levels of mitotic activity in all cases. In sharp contrast, all squamous morules were devoid of sex hormone receptors and had undetectable or extremely low-proliferation rates. When mutated, the same specific PTEN mutation was detected in squamous and glandular elements, indicating that both are of common lineage. The clinical and laboratory data are consistent with a model of morule biology in which squamous morules are a hormonally incompetent subpopulation of endometrial glandular lesions. Isolated morules might result from artifactual displacement from their native glandular context, or selective hormonally induced regression of the glandular but not squamous components over time. Subsequent cancer risk, as promoted by estrogens, is greatest when the glandular component has the appearance of endometrial intraepithelial

  9. Squamous Morules Are Functionally Inert Elements of Premalignant Endometrial Neoplasia

    PubMed Central

    Lin, Ming-Chieh; Lomo, Lesley; Baak, Jan P. A.; Eng, Charis; Ince, Tan A.; Crum, Christopher P.; Mutter, George L.

    2008-01-01

    Squamous morules are a common component of premalignant glandular lesions that are followed by glandular, rather than squamous, carcinomas. We tested the hypothesis that the appearance of glands associated with morules predicts cancer risk, and undertook molecular testing to determine the clonal and hormonal response properties of admixed squamous and glandular elements. 66 patients with squamous morules in an index endometrial biopsy had followup clinical data (average followup: interval 31 months, 2.5 biopsies) showing development of carcinoma in 11% (7/66) of cases. The histological appearance of morule-associated glands in the index biopsy was significantly associated with this clinical outcome, with the majority (71%, 5/7) of cancer occurrences following an overtly premalignant lesion (Endometrial Intraepithelial Neoplasia) with squamous morules. Eight endometrial intraepithelial neoplasias with squamous morules were examined by immunohistochemistry for estrogen and progesterone receptors and mitotic activity (Ki-67 antigen percent stained). Glandular components had abundant estrogen and progesterone receptors, and high levels of mitotic activity in all cases. In sharp contrast, all squamous morules were devoid of sex hormone receptors and had undetectable or extremely low proliferation rates. When mutated, the same specific PTEN mutation was detected in squamous and glandular elements, indicating that both are of common lineage. The clinical and laboratory data are consistent with a model of morule biology in which squamous morules are a hormonally incompetent subpopulation of endometrial glandular lesions. Isolated morules might result from artifactual displacement from their native glandular context, or selective hormonally induced regression of the glandular but not squamous components over time. Subsequent cancer risk, as promoted by estrogens, is greatest when the glandular component has the appearance of endometrial intraepithelial neoplasia. Even

  10. 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

  11. Ultrasound in assisted reproduction: a call to fill the endometrial gap.

    PubMed

    Hershko-Klement, Anat; Tepper, Ronnie

    2016-06-01

    Ultrasound offers essential details and an overall view of the anatomic features of the reproductive organs, as well as physiologic assessment. There is still a great gap, however, in our understanding and interpretation of endometrial sonographic findings. Endometrial thickness, growth, and sonographic patterns have been repeatedly tested and compared with pregnancy rates in IVF cycles, yielding conflicting results. Generally, the data accrued so far suggest refraining from clinical decisions based solely on endometrial thickness. The three-layer ultrasound pattern reflects normal follicular/proliferative dynamics, and its presence in the pre-hCG period was reported to carry a better outcome: Significantly higher clinical pregnancy rates were found in patients with this pattern on the day of hCG administration among IVF cohorts. Subendometrial contractility (endometrial "waves") offers a tool that can be used in cases of repeated implantation failure in patients reporting cramps around the planned time of embryo transfer, or as a reassuring modality to assess uterine quiescence during preparations for embryo transfer. We support the creation of an integrated endometrial score incorporating conservative endometrial measurements, endometrial-myometrial junction studies, and endometrial contractility, as well as new concepts that remain to be tested, such as endometrial surface area. Such scores may enable us to improve the effectiveness of endometrial ultrasound imaging in the clinical setting. PMID:27140291

  12. Effect of Endometrial Injury on Secretion of Endometrial Cytokines and IVF Outcomes in Women with Unexplained Subfertility

    PubMed Central

    Liang, Yu; Han, Junyan; Jia, Chanwei; Ma, Yanmin; Lan, Yonglian; Li, Ying; Wang, Shuyu

    2015-01-01

    In order to determine the effect of endometrial injury (EI) on in vitro fertilization (IVF) outcomes in women with unexplained subfertility and explore the relationship between EI and endometrial inflammatory cytokines, 66 women with unexplained subfertility undergoing IVF treatment were recruited. 38 patients in the EI group underwent EI in the mid-luteal phase of the cycle and 28 patients in the non-EI (NEI) group. According to the pregnancy outcome, the NEI and EI groups were divided into NEI-nonpregnant (NEI-NP), NEI-pregnant (NEI-P), EI-NP, and EI-P. All patients underwent aspiration of endometrial secretions immediately before embryo transfer. The concentrations of ten mediators were measured using Milliplex Magnetic Bead assay. The clinical pregnancy was significantly higher in the EI than in the NEI group. The concentrations of interleukin- (IL-) 6, IL-8, IL-12 (p70), IL-13, interferon- (IFN-) γ, monocyte chemotactic protein- (MCP-) 1, and vascular endothelial growth factor (VEGF) were significantly higher in the EI than the NEI group. The expression of IFN-γ and VEGF in the EI-P was significantly increased compared to the EI-NP group. These findings suggest that, in women with unexplained subfertility, endometrial injury might be a potential method to improve clinical pregnancy rates by promoting the expression of IFN-γ and VEGF. PMID:26586929

  13. Effect of Endometrial Injury on Secretion of Endometrial Cytokines and IVF Outcomes in Women with Unexplained Subfertility.

    PubMed

    Liang, Yu; Han, Junyan; Jia, Chanwei; Ma, Yanmin; Lan, Yonglian; Li, Ying; Wang, Shuyu

    2015-01-01

    In order to determine the effect of endometrial injury (EI) on in vitro fertilization (IVF) outcomes in women with unexplained subfertility and explore the relationship between EI and endometrial inflammatory cytokines, 66 women with unexplained subfertility undergoing IVF treatment were recruited. 38 patients in the EI group underwent EI in the mid-luteal phase of the cycle and 28 patients in the non-EI (NEI) group. According to the pregnancy outcome, the NEI and EI groups were divided into NEI-nonpregnant (NEI-NP), NEI-pregnant (NEI-P), EI-NP, and EI-P. All patients underwent aspiration of endometrial secretions immediately before embryo transfer. The concentrations of ten mediators were measured using Milliplex Magnetic Bead assay. The clinical pregnancy was significantly higher in the EI than in the NEI group. The concentrations of interleukin- (IL-) 6, IL-8, IL-12 (p70), IL-13, interferon- (IFN-) γ, monocyte chemotactic protein- (MCP-) 1, and vascular endothelial growth factor (VEGF) were significantly higher in the EI than the NEI group. The expression of IFN-γ and VEGF in the EI-P was significantly increased compared to the EI-NP group. These findings suggest that, in women with unexplained subfertility, endometrial injury might be a potential method to improve clinical pregnancy rates by promoting the expression of IFN-γ and VEGF.

  14. 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.

  15. 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

  16. Effect of Endometrial Injury on Secretion of Endometrial Cytokines and IVF Outcomes in Women with Unexplained Subfertility.

    PubMed

    Liang, Yu; Han, Junyan; Jia, Chanwei; Ma, Yanmin; Lan, Yonglian; Li, Ying; Wang, Shuyu

    2015-01-01

    In order to determine the effect of endometrial injury (EI) on in vitro fertilization (IVF) outcomes in women with unexplained subfertility and explore the relationship between EI and endometrial inflammatory cytokines, 66 women with unexplained subfertility undergoing IVF treatment were recruited. 38 patients in the EI group underwent EI in the mid-luteal phase of the cycle and 28 patients in the non-EI (NEI) group. According to the pregnancy outcome, the NEI and EI groups were divided into NEI-nonpregnant (NEI-NP), NEI-pregnant (NEI-P), EI-NP, and EI-P. All patients underwent aspiration of endometrial secretions immediately before embryo transfer. The concentrations of ten mediators were measured using Milliplex Magnetic Bead assay. The clinical pregnancy was significantly higher in the EI than in the NEI group. The concentrations of interleukin- (IL-) 6, IL-8, IL-12 (p70), IL-13, interferon- (IFN-) γ, monocyte chemotactic protein- (MCP-) 1, and vascular endothelial growth factor (VEGF) were significantly higher in the EI than the NEI group. The expression of IFN-γ and VEGF in the EI-P was significantly increased compared to the EI-NP group. These findings suggest that, in women with unexplained subfertility, endometrial injury might be a potential method to improve clinical pregnancy rates by promoting the expression of IFN-γ and VEGF. PMID:26586929

  17. CDC2 mediates progestin initiated endometrial stromal cell proliferation: a PR signaling to gene expression independently of its binding to chromatin.

    PubMed

    Vallejo, Griselda; La Greca, Alejandro D; Tarifa-Reischle, Inti C; Mestre-Citrinovitz, Ana C; Ballaré, Cecilia; Beato, Miguel; Saragüeta, Patricia

    2014-01-01

    Although non-genomic steroid receptor pathways have been studied over the past decade, little is known about the direct gene expression changes that take place as a consequence of their activation. Progesterone controls proliferation of rat endometrial stromal cells during the peri-implantation phase of pregnancy. We showed that picomolar concentration of progestin R5020 mimics this control in UIII endometrial stromal cells via ERK1-2 and AKT activation mediated by interaction of Progesterone Receptor (PR) with Estrogen Receptor beta (ERb) and without transcriptional activity of endogenous PR and ER. Here we identify early downstream targets of cytoplasmic PR signaling and their possible role in endometrial stromal cell proliferation. Microarray analysis of global gene expression changes in UIII cells treated for 45 min with progestin identified 97 up- and 341 down-regulated genes. The most over-represented molecular functions were transcription factors and regulatory factors associated with cell proliferation and cell cycle, a large fraction of which were repressors down-regulated by hormone. Further analysis verified that progestins regulate Ccnd1, JunD, Usf1, Gfi1, Cyr61, and Cdkn1b through PR-mediated activation of ligand-free ER, ERK1-2 or AKT, in the absence of genomic PR binding. ChIP experiments show that progestin promoted the interaction of USF1 with the proximal promoter of the Cdc2 gene. Usf1 knockdown abolished Cdc2 progestin-dependent transcriptional regulation and cell proliferation, which also blocked Cdc2 knockdown. We conclude that progestin-induced proliferation of endometrial stromal cells is mediated by ERK1-2 and AKT dependent early regulation of USF1, which directly induces Cdc2. To our knowledge, this is the first description of early target genes of progestin-activated classical PR via crosstalk with protein kinases and independently of hormone receptor binding to the genomic targets. PMID:24859236

  18. 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.

  19. 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.

  20. 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.

  1. A Murine Uterine Transcriptome, Responsive to Steroid Receptor Coactivator-2, Reveals Transcription Factor 23 as Essential for Decidualization of Human Endometrial Stromal Cells1

    PubMed Central

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

    2014-01-01

    ABSTRACT 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-2flox/flox (SRC-2f/f [control]) and PRcre/+/SRC-2flox/flox (SRC-2d/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. PMID

  2. 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.

  3. 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

  4. 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

  5. The accuracy of endometrial sampling in women with postmenopausal bleeding: a systematic review and meta-analysis.

    PubMed

    van Hanegem, Nehalennia; Prins, Marileen M C; Bongers, Marlies Y; Opmeer, Brent C; Sahota, Daljit Singh; Mol, Ben Willem J; Timmermans, Anne

    2016-02-01

    Postmenopausal bleeding (PMB) can be the first sign of endometrial cancer. In case of thickened endometrium, endometrial sampling is often used in these women. In this systematic review, we studied the accuracy of endometrial sampling for the diagnoses of endometrial cancer, atypical hyperplasia and endometrial disease (endometrial pathology, including benign polyps). We systematically searched the literature for studies comparing the results of endometrial sampling in women with postmenopausal bleeding with two different reference standards: blind dilatation and curettage (D&C) and hysteroscopy with histology. We assessed the quality of the detected studies by the QUADAS-2 tool. For each included study, we calculated the fraction of women in whom endometrial sampling failed. Furthermore, we extracted numbers of cases of endometrial cancer, atypical hyperplasia and endometrial disease that were identified or missed by endometrial sampling. We detected 12 studies reporting on 1029 women with postmenopausal bleeding: five studies with dilatation and curettage (D&C) and seven studies with hysteroscopy as a reference test. The weighted sensitivity of endometrial sampling with D&C as a reference for the diagnosis of endometrial cancer was 100% (range 100-100%) and 92% (71-100) for the diagnosis of atypical hyperplasia. Only one study reported sensitivity for endometrial disease, which was 76%. When hysteroscopy was used as a reference, weighted sensitivities of endometrial sampling were 90% (range 50-100), 82% (range 56-94) and 39% (21-69) for the diagnosis of endometrial cancer, atypical hyperplasia and endometrial disease, respectively. For all diagnosis studied and the reference test used, specificity was 98-100%. The weighted failure rate of endometrial sampling was 11% (range 1-53%), while insufficient samples were found in 31% (range 7-76%). In these women with insufficient or failed samples, an endometrial (pre) cancer was found in 7% (range 0-18%). In women with

  6. 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. PMID:24962421

  7. Racial microaggressions and difficult dialogues on race in the classroom.

    PubMed

    Sue, Derald Wing; Lin, Annie I; Torino, Gina C; Capodilupo, Christina M; Rivera, David P

    2009-04-01

    A qualitative study supports the observation that difficult dialogues on race and racism are often triggered by racial microaggressions that make their appearance in classroom encounters or educational activities and materials. Difficult dialogues are filled with strong powerful emotions that may prove problematic to both students and teachers. When poorly handled by teachers, difficult dialogues can assail the personal integrity of students of color while reinforcing biased worldviews of White students. The success or failure of facilitating difficult dialogues on race is intimately linked to the characteristics and actions of instructors and their ability to recognize racial microaggressions. Implications regarding specific education and training recommendations are presented.

  8. 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.

  9. Methylated DNA collected by tampons--a new tool to detect endometrial cancer.

    PubMed

    Fiegl, Heidi; Gattringer, Conny; Widschwendter, Andreas; Schneitter, Alois; Ramoni, Angela; Sarlay, Daniela; Gaugg, Inge; Goebel, Georg; Müller, Hannes M; Mueller-Holzner, Elisabeth; Marth, Christian; Widschwendter, Martin

    2004-05-01

    This proof of principle study aimed to define a new and simple strategy for detection of endometrial cancer using epigenetic markers. We investigated DNA isolated from vaginal secretion collected from tampon for aberrant methylation of five genes (CDH13, HSPA2, MLH1, RASSF1A, and SOCS2) using MethyLight in 15 patients with endometrial cancer and 109 patients without endometrial cancer. All endometrial cancer patients revealed three or more methylated genes, whereas 91% (99 of 109) of the patients without endometrial cancer had no or fewer than three genes methylated in their vaginal secretion. The methods developed in this study provide the basis for a prospective clinical trial to screen asymptomatic women who are at high risk for endometrial cancer.

  10. Surgical Management of Endometrial Polyps in Infertile Women: A Comprehensive Review

    PubMed Central

    Pereira, Nigel; Petrini, Allison C.; Lekovich, Jovana P.; Elias, Rony T.; Spandorfer, Steven D.

    2015-01-01

    Endometrial polyps are benign localized lesions of the endometrium, which are commonly seen in women of reproductive age. Observational studies have suggested a detrimental effect of endometrial polyps on fertility. The natural course of endometrial polyps remains unclear. Expectant management of small and asymptomatic polyps is reasonable in many cases. However, surgical resection of endometrial polyps is recommended in infertile patients prior to treatment in order to increase natural conception or assisted reproductive pregnancy rates. There is mixed evidence regarding the resection of newly diagnosed endometrial polyps during ovarian stimulation to improve the outcomes of fresh in vitro fertilization cycles. Hysteroscopy polypectomy remains the gold standard for surgical treatment. Evidence regarding the cost and efficacy of different methods for hysteroscopic resection of endometrial polyps in the office and outpatient surgical settings has begun to emerge. PMID:26301260

  11. Proliferation and responsiveness to estrogen of human endometrial cancer cells under serum-free culture conditions.

    PubMed

    Holinka, C F; Anzai, Y; Hata, H; Kimmel, N; Kuramoto, H; Gurpide, E

    1989-06-15

    Studies of hormonal growth regulation in cultured human endometrial cancer cells are limited by the requirement of exogenous growth factors, usually supplied by addition of serum. The present report provides evidence that estradiol can stimulate proliferation of endometrial cancer cells of the Ishikawa line in the absence of serum or added growth factors. Mitogenic effects of estrogen were demonstrated in two different experimental systems, in cells attached to the substratum of mammalian tissue culture dishes, and in cells forming colonies in soft agar under anchorage-independent conditions. Addition of estradiol to a mixture of serum-free, phenol red-free Dulbecco's minimal essential medium and Ham's F-12 medium, supplemented with L-glutamine and 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid [basal medium: (BM)] significantly increased the proliferation of cells attached to culture dishes. Dose-response experiments revealed maximal estradiol stimulation at 10 nM; significant responses were also observed at 1 nM and at 100 nM concentrations. The mitogenic effect of 10 nM estradiol was comparable to that of 1% charcoal-treated fetal bovine serum and the two effects were additive. The presence of estradiol in serum-free BM resulted in a shortening of the doubling time of exponentially proliferating cells from 38 to 29 h. From the labeling index, measured after exposure to a pulse of [3H]thymidine, and from the mitotic index, both determined in exponentially proliferating cells, the lengths of the S and M phases were calculated to be 11 and 1 h, respectively. From these data it was estimated that estradiol shortened the G1 phase by approximately 40%, from 22 to 13 h. Estradiol doubled the colony formation efficiency of cells plated in BM containing 0.3% agar in the absence of serum as well as in the presence of 1% charcoal-treated fetal bovine serum. The stimulation of colony formation by estradiol was influenced by medium components, since no effects were

  12. Progestins Upregulate FKBP51 Expression in Human Endometrial Stromal Cells to Induce Functional Progesterone and Glucocorticoid Withdrawal: Implications for Contraceptive- Associated Abnormal Uterine Bleeding

    PubMed Central

    Guzeloglu Kayisli, Ozlem; Kayisli, Umit A.; Basar, Murat; Semerci, Nihan; Schatz, Frederick; Lockwood, Charles J.

    2015-01-01

    Use of long-acting progestin only contraceptives (LAPCs) offers a discrete and highly effective family planning method. Abnormal uterine bleeding (AUB) is the major side effect of, and cause for, discontinuation of LAPCs. The endometria of LAPC-treated women display abnormally enlarged, fragile blood vessels, decreased endometrial blood flow and oxidative stress. To understanding to mechanisms underlying AUB, we propose to identify LAPC-modulated unique gene cluster(s) in human endometrial stromal cells (HESCs). Protein and RNA isolated from cultured HESCs treated 7 days with estradiol (E2) or E2+ medroxyprogesterone acetate (MPA) or E2+ etonogestrel (ETO) or E2+ progesterone (P4) were analyzed by quantitative Real-time (q)-PCR and immunoblotting. HSCORES were determined for immunostained-paired endometria of pre-and 3 months post-Depot MPA (DMPA) treated women and ovariectomized guinea pigs (GPs) treated with placebo or E2 or MPA or E2+MPA for 21 days. In HESCs, whole genome analysis identified a 67 gene group regulated by all three progestins, whereas a 235 gene group was regulated by E2+ETO and E2+MPA, but not E2+P4. Ingenuity pathway analysis identified glucocorticoid receptor (GR) activation as one of upstream regulators of the 235 MPA and ETO-specific genes. Among these, microarray results demonstrated significant enhancement of FKBP51, a repressor of PR/GR transcriptional activity, by both MPA and ETO. q-PCR and immunoblot analysis confirmed the microarray results. In endometria of post-DMPA versus pre-DMPA administered women, FKBP51 expression was significantly increased in endometrial stromal and glandular cells. In GPs, E2+MPA or MPA significantly increased FKBP51 immunoreactivity in endometrial stromal and glandular cells versus placebo- and E2-administered groups. MPA or ETO administration activates GR signaling and increases endometrial FKBP51 expression, which could be one of the mechanisms causing AUB by inhibiting PR and GR-mediated transcription

  13. A critical assessment on the role of sentinel node mapping in endometrial cancer

    PubMed Central

    Ditto, Antonino; Martinelli, Fabio; Signorelli, Mauro; Perotto, Stefania; Lorusso, Domenica; Raspagliesi, Francesco

    2015-01-01

    Endometrial cancer is the most common gynecologic malignancy in the developed countries. Although the high incidence of this occurrence no consensus, about the role of retroperitoneal staging, still exists. Growing evidence support the safety and efficacy of sentinel lymph node mapping. This technique is emerging as a new standard for endometrial cancer staging procedures. In the present paper, we discuss the role of sentinel lymph node mapping in endometrial cancer, highlighting the most controversies features. PMID:26508591

  14. 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 ...

  15. 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,…

  16. Rimac: A Natural-Language Dialogue System that Engages Students in Deep Reasoning Dialogues about Physics

    ERIC Educational Resources Information Center

    Katz, Sandra; Jordan, Pamela; Litman, Diane

    2011-01-01

    The natural-language tutorial dialogue system that the authors are developing will allow them to focus on the nature of interactivity during tutoring as a malleable factor. Specifically, it will serve as a research platform for studies that manipulate the frequency and types of verbal alignment processes that take place during tutoring, such as…

  17. Is the pineal gland involved in the pathogenesis of endometrial carcinoma.

    PubMed

    Sandyk, R; Anastasiadis, P G; Anninos, P A; Tsagas, N

    1992-01-01

    The pathogenesis of endometrial carcinoma, which is the most common malignant neoplasm of the female genital tract, is unknown. It is believed that a prolonged period of increased estrogenic exposure unopposed by progesterone may underlie the malignant transformation of the endometrial cells. In the following communication, we propose that deficient melatonin functions may be an additional endocrine factor implicated in the pathogenesis of endometrial carcinoma. This hypothesis is based on the observations that: (a) melatonin has antiestrogenic properties; (b) melatonin stimulates progesterone production which opposes the action of estrogens; (c) an increased rate of endometrial hyperplasia, a premalignant condition, has been noted during the winter, a time of year associated with diminished melatonin secretion; (d) an increased incidence of anovulatory cycles, which is a risk factor for endometrial carcinoma, occurs in the winter; (e) melatonin secretion decreases sharply during the menopause, a period associated with an increased risk of endometrial carcinoma; (f) obesity, which is a major risk factor for endometrial carcinoma, is associated with impaired circadian melatonin secretion; (g) diabetes mellitus, which is an additional risk factor for endometrial carcinoma, is associated with decreased melatonin secretion and an increased rate of pineal calcification; and (h) the prevalence of endometrial carcinoma is lower in the black population compared to the white population. Similarly, the incidence of pineal calcification, which reflects the secretory activity of the gland, is significantly lower in the African and American black populations as compared to the white population.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1342018

  18. Is the pineal gland involved in the pathogenesis of endometrial carcinoma.

    PubMed

    Sandyk, R; Anastasiadis, P G; Anninos, P A; Tsagas, N

    1992-01-01

    The pathogenesis of endometrial carcinoma, which is the most common malignant neoplasm of the female genital tract, is unknown. It is believed that a prolonged period of increased estrogenic exposure unopposed by progesterone may underlie the malignant transformation of the endometrial cells. In the following communication, we propose that deficient melatonin functions may be an additional endocrine factor implicated in the pathogenesis of endometrial carcinoma. This hypothesis is based on the observations that: (a) melatonin has antiestrogenic properties; (b) melatonin stimulates progesterone production which opposes the action of estrogens; (c) an increased rate of endometrial hyperplasia, a premalignant condition, has been noted during the winter, a time of year associated with diminished melatonin secretion; (d) an increased incidence of anovulatory cycles, which is a risk factor for endometrial carcinoma, occurs in the winter; (e) melatonin secretion decreases sharply during the menopause, a period associated with an increased risk of endometrial carcinoma; (f) obesity, which is a major risk factor for endometrial carcinoma, is associated with impaired circadian melatonin secretion; (g) diabetes mellitus, which is an additional risk factor for endometrial carcinoma, is associated with decreased melatonin secretion and an increased rate of pineal calcification; and (h) the prevalence of endometrial carcinoma is lower in the black population compared to the white population. Similarly, the incidence of pineal calcification, which reflects the secretory activity of the gland, is significantly lower in the African and American black populations as compared to the white population.(ABSTRACT TRUNCATED AT 250 WORDS)

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

    ClinicalTrials.gov

    2016-11-02

    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

  20. 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

  1. The PRB-dependent FOXO1/IGFBP-1 axis is essential for progestin to inhibit endometrial epithelial growth.

    PubMed

    Nakamura, Mitsuhiro; Takakura, Masahiro; Fujii, Reina; Maida, Yoshiko; Bono, Yukiko; Mizumoto, Yasunari; Zhang, Xian; Kiyono, Tohru; Kyo, Satoru

    2013-08-01

    Progestin inhibits the growth of normal and cancerous endometria via the progesterone receptor (PR), but the distinct functions and signalings of PR subtypes have not been fully understood. The aim of the present study was to dissect the key pathways of progestin to inhibit endometrial epithelial growth. Immortalized endometrial epithelial cells (EM-E6/E7/TERT) with stable PRA or PRB expression were established and used for the experiments. In vitro growth inhibition by progestin was mainly observed in EM-E6/E7/TERT cells with PRB rather than those with PRA. RT-PCR assay confirmed that FOXO1, a key gene for progestin action, was up-regulated by progestin in a PRB-dependent manner. cDNA microarray analysis identified IGFBP-1, which contains FOXO1 binding sites on its promoter, to be induced by medroxyprogesterone acetate (MPA) in EM-E6/E7/TERT cells with PRB but not with PRA. siRNA knockdown of FOXO1 disturbed the induction of IGFBP-1 by MPA, while IGFBP-1 knockdown showed no effect on MPA-induced FOXO1 expression, indicating that FOXO1 is an upstream regulator of IGFBP-1. Luciferase reporter assays showed that MPA activated the IGFBP-1 promoter, which was cancelled by FOXO1 knockdown. Chromatin immunoprecipitation assay confirmed the in vivo binding of FOXO1 to the core promoter of IGFBP-1. IGFBP-1 knockdown significantly attenuated the growth inhibitory effects of MPA. The FOXO1/IGFBP-1 axis is essential for PRB-dependent growth inhibition of endometrial epithelial cells, offering a potential therapeutic clue to enhance the progestin effect.

  2. Ultrastructural aspects of endometrial surface in Kartagener's syndrome.

    PubMed

    Marchini, M; Losa, G A; Nava, S; Di Nola, G; Fedele, L

    1992-02-01

    The endometrium of an infertile patient with Kartagener's syndrome showed initial secretory phase characteristics at SEM, whereas TEM analysis demonstrated several alterations in the central and peripheral microtubular distribution in 87% of the cilia examined. Such aspects seemed appropriate for a normal implantation, but the ciliary immotility or dyskinesia could cause an altered flow of the endometrial secretions and compromise the upstream movement of the spermatozoa.

  3. Xanthogranulomatous Endometritis: An Unusual Pathological Entity Mimicking Endometrial Carcinoma

    PubMed Central

    Makkar, M; Gill, MK; Singh, DP

    2013-01-01

    Xanthogranulomatous endometritis is an unusual pathological entity mimicking endometrial carcinoma. This shows sheets of foamy histiocytes alongwith other inflammatory cells. We, hereby, report a case of 45 year multigravida female with irregular menstrual history, clinically diagnosed as carcinoma and histopathologically turned out as xanthogranulomatous endometritis. So, this condition should always be dealt with caution, and pathologists and clinicians should be aware of it. PMID:24349850

  4. 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

  5. Xanthogranulomatous Endometritis: A Challenging Imitator of Endometrial Carcinoma

    PubMed Central

    Doğan-Ekici, A. Işın; Usubütün, Alp; Küçükali, Türkan; Ayhan, Ali

    2007-01-01

    Xanthogranulomatous inflammation is a distinguished histopathological entity affecting several organs, predominantly the kidney and gallbladder. So far, only a small number of cases of xanthogranulomatous inflammation occurring in female genital tract have been described, most frequently affecting the endometrium and histologically characterized by replacement of endometrium by xanthogranulomatous inflammation composed of abundant foamy histiocytes, siderophages, giant cells, fibrosis, calcification and accompanying polymorphonuclear leucocytes, plasma cells and lymphocytes of polyclonal origin. We present a case of a 69-year-old female complained of post menopausal bleeding and weight loss. Clinical preliminary diagnoses were endometrial carcinoma or hyperplasia and ultrasound was supposed to be endometrial malignancy, hyperplasia or pyometra by radiologist. Histopathological examination of uterus revealed xanthogranulomatous endometritis. Since xanthogranulomatous endometritis may mimic endometrial malignancy clinically and pathologically as a result of the replacement of the endometrium and occasionally invasion of the myometrium by friable yellowish tissue composed of histiocytes, knowledge of this unusual inflammatory disease is needed for both clinicians and pathologists. PMID:17710239

  6. Endometrial echotexture variables in postpartum cows with subclinical endometritis.

    PubMed

    Polat, B; Cengiz, M; Cannazik, O; Colak, A; Oruc, E; Altun, S; Salar, S; Bastan, A

    2015-04-01

    The aim of this study was to evaluate endometrial echotexture changes on ultrasonographic digital images during subclinical endometritis using a computer-assisted image analysis program. Endometrial samples were collected from 140 Brown Swiss cows (days in milk = 35 ± 3) using a cytobrush method and classified as having a non-inflamed uterus (n = 66) and uterus with acute (n = 42), subacute (n = 21), and chronic (n = 11) inflammations. The mean cellular infiltration density was 0%, 31 ± 5%, 37 ± 6%, and 16 ± 8% for cows with non-inflamed uterus and cows with acute, subacute, and chronic uterine inflammations (P < 0.0001). As the cell infiltration density increased, both cervical diameter and mean gray level did not change. There were a liner decrease in homogeneity and a linear increase in contrast in response to increased cellular infiltration density. The sensitivity and specificity were 79.73% and 46.97% for the homogeneity value and 59.46% and 69.70% for the contrast value, respectively. In conclusion, monitoring endometrial echotexture alterations, especially homogeneity and contrast, changed depending on the cellular density and inflammation status and may be potential diagnostic markers for subclinical endometritis in cows. PMID:25721562

  7. 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'. PMID:19891664

  8. Unusual inflammation in gynecologic pathology associated with defective endometrial receptivity.

    PubMed

    Kitaya, Kotaro; Yasuo, Tadahiro; Tada, Yoshihiro; Hayashi, Terumi; Iwaki, Yuri; Karita, Masako; Funabiki, Miyako; Taguchi, Sagiri; Spillers, Dustin; Nakamura, Yoshitaka; Yamada, Hisao

    2014-09-01

    Human cycling endometrium displays a series of periodic transitions unique to this mucosal tissue, which includes rapid proliferation, secretory transformation, physiological angiogenesis, interstitial edema, and menstrual shedding. Among these properties of the endometrium are the inflammatory changes that occur dynamically across the menstrual cycle. Immunocompetent cell composition and inflammatory gene expression pattern in the human endometrium drastically fluctuate from the proliferative phase to the secretory phase, particularly at the time of ovulation. These local immune responses are fine-tuned by the direct or indirect action of two representative ovarian steroids, estradiol and progesterone, and are essential for successful blastocyst implantation. Meanwhile, studies have been accumulating the evidence that such physiological endometrial inflammatory status is altered in the presence of certain gynecologic pathologies. Given that blastocysts are semi-allografts for maternal tissue, even subtle alterations in endometrial immunity potentially have a negative impact on implantation process. In this article, we aimed to review and discuss the physiological and pathological mucosal inflammatory conditions that can affect endometrial receptivity. PMID:24771248

  9. 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…

  10. 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…

  11. 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…

  12. What We Hear Is Meaning Too: Deconstruction, Dialogue, and Music

    ERIC Educational Resources Information Center

    Schmidt, Patrick

    2012-01-01

    The concept of dialogue as deconstruction introduced in this article is prompted by two concerns: first, the multiplicity of representation in contemporary society, and second, the need to address rather than resolve the other as a central premise for learning. Dialogue as deconstruction is seen as an impactful element in destabilizing sequential…

  13. Achieving Inclusion through CLAD: Collaborative Learning Assessment through Dialogue

    ERIC Educational Resources Information Center

    Fitch, E. Frank; Hulgin, Kathleen M.

    2008-01-01

    This study measures the effectiveness of Collaborative Learning Assessment through Dialogue (CLAD) on reading achievement in inclusive classrooms in the USA. The CLAD process involved students collaboratively completing multiple-choice quizzes, using dialogue and critical thinking to reach consensus and receiving immediate feedback on their…

  14. Students' Evaluations of Dialogue Journals: Perspectives on Classroom Themes

    ERIC Educational Resources Information Center

    Ewald, Jennifer

    2006-01-01

    A dialogue journal is a series of collaborative, ongoing reflections between a teacher and a student, interacting in a forum of written, informal "conversation". Used at all levels ranging from K-12 to post-graduate contexts and in disciplines such as language, history, biology, mathematics, and teacher education, dialogue journals have…

  15. Campus-Based University Students' Use of Dialogue

    ERIC Educational Resources Information Center

    Gorsky, Paul; Caspi, Avner; Trumper, Ricardo

    2006-01-01

    This investigation explores the kinds of study strategies used by campus-based university students in terms of the dialogues they engaged in while learning physics and chemistry in both large and small classes. Research objectives were threefold: (1) to document what dialogue types, mediated through which resources, were generally utilized by…

  16. Developing a Model for Ethical Dialogue and Decisionmaking.

    ERIC Educational Resources Information Center

    Roehl, Janet; Murphy, Shelia; Burns, Susan

    2000-01-01

    Suggests that a practical model for dialogue and decisionmaking in ethics needs to be developed, which is intended for widespread use within organizations and communities. Outlines objectives of an effective model, and basic questions that it must respond to. Discusses piloting the model, as well as facilitation of dialogue, development of…

  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. 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…

  19. 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" practised…

  20. 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…

  1. 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…

  2. 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 humanity and…

  3. 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…

  4. 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…

  5. 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…

  6. A Dialogue on Liberal Learning in Professional Education.

    ERIC Educational Resources Information Center

    Association of American Colleges, Washington, DC.

    The third in a series of reports on AAC-sponsored dialogues on liberal learning is presented. This dialogue, focusing on the role of liberal learning in professional education, was designed for both teachers and administrators representing a variety of colleges of business, engineering, fine arts, and the health sciences. In the first case study,…

  7. Speaking across Difference in Community Dialogues on Affirmative Action Policy

    ERIC Educational Resources Information Center

    Davidson, Kristen L.; Moses, Michele S.

    2012-01-01

    This study investigated the relevance of participants' social group differences with regard to the processes and outcomes of community dialogues on affirmative action. We found that participants' professional status was most salient to both the quantity of participants' contributions as well as their persuasiveness within the dialogues, with…

  8. 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…

  9. Capturing Mentor Teachers' Reflective Moments during Mentoring Dialogues

    ERIC Educational Resources Information Center

    Crasborn, Frank; Hennissen, Paul; Brouwer, Niels; Korthagen, Fred; Bergen, Theo

    2010-01-01

    The main goal of the current study is to capture differential frequencies of mentor teachers' reflective moments, as indicators of different levels of consciousness in mentor teachers' use and acquisition of supervisory skills during mentoring dialogues. For each of the 30 participants, two mentoring dialogues were analyzed: one before and one…

  10. 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…

  11. Dialogue as a Means of Learning and Teaching

    ERIC Educational Resources Information Center

    Baskas, Richard S.

    2010-01-01

    The purpose of this paper is to examine how dialogue is involved in learning and teaching in the classroom. Dialogue is present in many forms as it is used in group interactions, used with technology and how pre-service teachers communicate with their school supervisors during their training. Research was conducted through Educational Resources…

  12. 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…

  13. 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…

  14. 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…

  15. 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…

  16. 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…

  17. 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…

  18. "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.…

  19. Esperanza y Poder: Democratic Dialogue and Authentic Parent Involvement

    ERIC Educational Resources Information Center

    Stratton, Susan

    2006-01-01

    This study explored ways to increase authentic participation of Mexican American parents in the education of their children. It focused on direct dialogue between Spanish-speaking parents and English-speaking school personnel and how dialogue facilitated group development. The design of the study included phenomenological inquiry and action…

  20. 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…

  1. 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)

  2. Introductory CAI Dialogue in Differential Calculus for Freshman Physics

    ERIC Educational Resources Information Center

    Kalman, C. S.; And Others

    1974-01-01

    A project on computer based dialogue for freshmen is described and evaluated. The dialogue utilizes a CAI language written in Fortran that allows a designer to easily write and edit questions at his own desk without the use of a terminal. (Author/DT)

  3. Facilitating Dialogue on Religion and Sexuality Using a Descriptive Approach

    ERIC Educational Resources Information Center

    McCarty, Richard W.

    2009-01-01

    Dialogue on religion and sexuality is difficult because these topics consist of deeply seated concepts of self, as well as one's relationship to other selves in the world. This chapter offers practical steps for creating and navigating difficult dialogues with respect to sexuality and religion. It suggests that partnership with departments,…

  4. Classroom Dialogue: A Systematic Review across Four Decades of Research

    ERIC Educational Resources Information Center

    Howe, Christine; Abedin, Manzoorul

    2013-01-01

    Recognizing that empirical research into classroom dialogue has been conducted for about 40?years, a review is reported of 225 studies published between 1972 and 2011. The studies were identified through systematic search of electronic databases and scrutiny of publication reference lists. They focus on classroom dialogue in primary and secondary…

  5. Facilitating Difficult Dialogues at the Intersections of Religious Privilege

    ERIC Educational Resources Information Center

    Watt, Sherry K.

    2009-01-01

    A core definition of a "difficult dialogue" is a verbal or written exchange of ideas or opinions among citizens within a community that centers on an awakening of potentially conflicting views about beliefs and values. As informed by Fried's definition of religious privilege (2007), difficult dialogue at the intersections of religious privilege…

  6. 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…

  7. 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.

  8. 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.

  9. Does dilation and curettage versus expectant management for spontaneous abortion in patients undergoing in vitro fertilization affect subsequent endometrial development?

    PubMed

    Moon, Kimberly S; Richter, Kevin S; Levy, Michael J; Widra, Eric A

    2009-11-01

    In in vitro fertilization patients, treatment of spontaneous abortion with dilation and curettage (D&C) versus expectant management has no long-term effect on subsequent endometrial development, as measured by change in endometrial thickness. A transient reduction in endometrial thickness was found within the first 6 months after D&C, which is a novel finding, but it is likely to have little or no effect on pregnancy rates given the small absolute effect on endometrial thickness.

  10. Does dilation and curettage versus expectant management for spontaneous abortion in patients undergoing in vitro fertilization affect subsequent endometrial development?

    PubMed

    Moon, Kimberly S; Richter, Kevin S; Levy, Michael J; Widra, Eric A

    2009-11-01

    In in vitro fertilization patients, treatment of spontaneous abortion with dilation and curettage (D&C) versus expectant management has no long-term effect on subsequent endometrial development, as measured by change in endometrial thickness. A transient reduction in endometrial thickness was found within the first 6 months after D&C, which is a novel finding, but it is likely to have little or no effect on pregnancy rates given the small absolute effect on endometrial thickness. PMID:19560759

  11. Relationships between Serum Luteinizing Hormone Level, Endometrial Thickness and Body Mass Index in Polycystic Ovary Syndrome Patients with and without Endometrial Hyperplasia

    PubMed Central

    Ramezanali, Fariba; Khalili, Gholamreza; Arabipoor, Arezoo; Bagheri Lankarani, Narges; Moini, Ashraf

    2016-01-01

    Background The endometrial hyperplasia measured by ultrasound in polycystic ovary syndrome (PCOS) women is strongly related to pathologic endometrial thickness, but there is no consensus on the relation between serum luteinizing hormone (LH) and either of these factors: pathologic endometrial hyperplasia and body mass index (BMI). Materials and Methods In this observational cross-sectional study, three hundred fifty infertile PCOS women were involved in this research. An endometrial biopsy was taken by using a pipelle instrument, regardless of menstrual cycle’s day and all samples were reported by the same pathologist. Basal serum LH level was compared between two subgroups (hyperplasia and non-hyperplasia). The intended population was divided into three groups according to BMI and basal serum LH, later on the comparison was made in three groups. Chi-square test was applied to compare nominal variables between groups. Mann-Whitney U, and one way ANOVA tests were used to compare means on the basis of the result of normality test. Results The frequency of endometrial hyperplasia was 2.6%. Endometrial thickness in the patients with endometrial hyperplasia was significantly higher than that of a normal endometrium (10.78 ± 3.70 vs. 7.90 ± 2.86 respectively, P=0.020). There was no relation between endometrial hyperplasia and serum LH (P=0.600). The ANOVA test showed serum LH levels were not the same among three BMI groups (P=0.007). Post hoc test was also performed. It showed that the LH level in normal BMI group was significantly higher than those of other groups (P=0.005 and P=0.004), but there was no statistical difference between overweight and obese groups (P=0.8). We found no relationship between BMI and endometrial thickness in PCOS patients (P=0.6). Conclusion Sonographic endometrial stripe thickness is predictive for endometrial hyperplasia in PCOS women. We could not find out any relationship between serum LH level and BMI with endometrial thickness in

  12. Genetic strain and reproductive status affect endometrial fatty acid concentrations.

    PubMed

    Meier, S; Peterson, A J; Mitchell, M D; Littlejohn, M; Walker, C G; Roche, J R

    2009-08-01

    Poor reproductive performance limits cow longevity in seasonal, pasture-based dairy systems. Few differences in ovarian dynamics have been reported in different strains of Holstein-Friesian cows, implying that the uterine environment may be a key component determining reproductive success. To test the hypothesis that the uterine environment differs among genetic strains of the Holstein-Friesian cow, endometrial fatty acids (FA) were analyzed from New Zealand (NZ), and North American (NA) Holstein-Friesian cows. The effect of reproductive status was also investigated, with cows from both Holstein-Friesian strains slaughtered on either d 17 of the estrous cycle (termed cyclic) or d 17 of pregnancy (after embryo transfer; termed pregnant). Endometrial tissues were collected from 22 cows (NZ pregnant, n = 6; NZ cyclic, n = 4; NA pregnant, n = 6; NA cyclic, n = 6), and FA composition was analyzed. Daily plasma progesterone concentrations, milk production, milk FA composition, body weight, and body condition score were determined. Milk yield (4% fat-corrected milk) was similar for the NZ (28.5 kg/d) and NA (29.3 kg/d; SE 2.07 kg/d) cows, but NZ cows had a greater mean milk fat percentage. Mean plasma progesterone concentrations were significantly greater in NZ cows. Plasma progesterone concentrations were similar in the pregnant and cyclic groups. Mean length of the trophoblast recovered from the pregnant cows (NZ: 20.8 +/- 2.84 cm; NA: 27.9 +/- 10.23 cm) was not affected by genetic strain. Endometrial tissues from NZ cows contained greater concentrations of C17:0, C20:3n-3, and total polyunsaturated FA. The endometria from pregnant cows contained greater concentrations of C17:0, C20:2, and C20:3n-6, and less C20:1, C20:2, C20:5n-3. The observed changes in endometrial FA between Holstein-Friesian cows of different genetic origins or reproductive states may reflect differences in endometrial function and may affect reproductive function.

  13. 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,…

  14. 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…

  15. 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. PMID:17911878

  16. 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

  17. 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

  18. Sophoricoside fails the embryo implantation by compromising the uterine endometrial receptivity at implantation "window" of pregnant mice.

    PubMed

    Zhou, Jianhong; Qu, Chengquan; Sun, Qi; Wu, Lisha; Liu, Yanglu; Yang, Zhirong; Zhang, Jie

    2014-08-01

    Sophoricoside (SOPH) is an isoflavone glycoside isolated from the fruits of Sophora japonica. Since its first isolation in 1961, there are rare findings about the effects of SOPH on reproductive system. In the present study, the pregnant mice administrated by different doses of SOPH were used to explore the effect of SOPH on embryo implantation, especially on the endometrial receptivity. The statistical results showed that the number of implanted embryos was gradually declining along the increasing dose of SOPH. When the administrated dose of SOPH was 600 mg/kg per day, great changes were observed in the exposed uterine morphology and up-regulated progesterone receptor (PR) and down-regulated estrogen receptor α (ERα), E-cadherin, matrix metalloproteinase-2 (MMP-2) and integrin β3 were also found in SOPH-exposed uterine. These findings demonstrated that SOPH exposure reduced the number of implanted embryos in a dose-dependent manner and failed the embryo implantation through altering the morphology of uterine and compromising the endometrial receptivity. PMID:24877640

  19. Expression Patterns of the Wnt Pathway Inhibitors Dickkopf3 and Secreted Frizzled-Related Proteins 1 and 4 in Endometrial Endometrioid Adenocarcinoma

    PubMed Central

    Eskander, Ramez N.; Ali, Shamshad; Dellinger, Thanh; Lankes, Heather A.; Randall, Leslie M.; Ramirez, Nilsa C.; Monk, Bradley J.; Walker, Joan L.; Eisenhauer, Eric; Hoang, Bang H.

    2016-01-01

    Objective The aim of the study was to determine the differential expression patterns of the wingless-type (Wnt) pathway inhibitors Dkk3 (Dickkopf 3), SFRP1 (secreted frizzled-related protein 1), and SFRP4 in normal müllerian tissue and endometrial endometrioid adenocarcinoma specimens. Methods Messenger RNA (mRNA) and protein levels of the Wnt pathway inhibitors Dkk3, SFRP1, and SFRP4 were evaluated by real-time reverse transcription–polymerase chain reaction and Western blot analysis. A total of 87 human tissue specimens were obtained from 60 women who participated in Gynecologic Oncology Group protocol 210. Twenty-seven normal müllerian tissues, 32 early-stage, and 28 advanced-stage endometrial endometrioid cancer specimens were analyzed. Results Median age for this cohort was 60 years, with median body mass index of 32 kg/m2. There was a difference in Dkk3 protein expression between normal müllerian tissues and primary endometrial endometrioid adenocarcinoma samples (P = 0.05). There was down-regulation of Dkk3, SFRP1, and SFRP4 mRNA expression in patients with high-grade disease (P = 0.08, 0.06, and 0.05, respectfully). Furthermore, a decrease in SFRP1 and SFPR4 mRNA expression was noted in patients with a diagnosis of locoregional and distant disease recurrence. Lastly, a trend toward decreased progression-free survival in patients with low Dkk3, SFRP1, and SFRP4 mRNA expression levels was noted. Conclusions Wnt pathway inhibitor (Dkk3, sFRP1, and/or sFRP4) expression was down-regulated in patients with high-grade disease and was associated with locoregional and distant disease recurrence. Despite sample size (power) limitations, these results support previous preclinical studies and may suggest a therapeutic role for Wnt signaling in endometrial cancer. PMID:26397159

  20. Stromal deletion of the APC tumor suppressor in mice triggers development of endometrial cancer

    PubMed Central

    Tanwar, Pradeep S.; Zhang, LiHua; Roberts, Drucilla J.; Teixeira, Jose M.

    2011-01-01

    The contribution of the stromal microenvironment to the progression of endometrial cancer (EC) has not been well explored. We have conditionally expressed a mutant allele of adenomatous polyposis coli (APCcKO) in murine uterine stroma cells to study its effect on uterine development and function. In addition to metrorrhagia, the mice develop complex atypical endometrial gland hyperplasia that progresses to endometrial carcinoma in situ and endometrial adenocarcinoma as evidenced by myometrial invasion. Stromal cells subjacent to the carcinoma cells express αSMA with fewer cells expressing PDGFR-α compared to normal stromal cells suggesting that the mutant stromal cells have acquired a more myofibroblastic phenotype, which have been described as cancer-associated fibroblasts and have been shown to induce carcinogenesis in other organ systems. Analyses of human EC specimens showed substantial αSMA expression in the stroma compared with normal endometrial stroma cells. We also show that APCcKO mutant uteri and human EC have decreased stromal levels of TGFβ and BMP activities and that the mutant uteri failed to respond to exogenous estradiol stimulation. The mutant stroma cells also had higher levels of VEGF and SDF signaling components and diminished expression of ERα and PR which is common in advanced stages of human EC and is an indicator of poor prognosis. Our results indicate that de novo mutation or loss of heterozygosity in stromal APC is sufficient to induce endometrial hyperplasia and endometrial carcinogenesis by mechanisms that are consistent with unopposed estrogen signaling in the endometrial epithelium. PMID:21363919

  1. The value of hysteroscopic biopsy in the diagnosis of endometrial polyps.

    PubMed

    Spadoto-Dias, Daniel; Bueloni-Dias, Flávia Neves; Elias, Leonardo Vieira; Leite, Nilton José; Modotti, Waldir Pereira; Lasmar, Ricardo Bassil; Dias, Rogério

    2016-07-01

    Several studies have demonstrated that the combination of hysteroscopy with endometrial biopsy is more accurate in differentiating endometrial polyps from endometrial hyperplasia and cancer. However, blind biopsy not always confirms hysteroscopic findings due to high rates of inadequate or insufficient material. The objective of this clinical, prospective, and comparative study was to establish a correlation between the histological results of office-based endometrial biopsies (hysteroscopically guided and blind) with the surgical polypectomy specimens. We evaluated 82 patients with hysteroscopic diagnosis of endometrial polyp, who randomly underwent hysteroscopically guided biopsy or blind biopsy, referred for surgical resection. A total of 36 women (43.9%) underwent hysteroscopically guided biopsy and 46 women (56.1%) underwent blind biopsy. The sensitivity of hysteroscopically guided biopsy for the diagnosis of endometrial polyps ranged between 35.3 and 36.8%, when carried out at the apex and base of the lesion, compared with 29.2% for blind biopsy. Specificity was 33.3, 50, and 60%, respectively, for each biopsy. The positive predictive values were 75, 77.8, and 87.5%, and negative predictive values were 8.3, 14.3, and 8.1% respectively, compared with surgical polypectomy specimens. The office-based endometrial biopsies had low diagnostic accuracy for endometrial polyps compared with surgical polypectomy specimens. PMID:27638896

  2. 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…

  3. Diagnostic utility of hepatocyte nuclear factor 1-beta immunoreactivity in endometrial carcinomas: lack of specificity for endometrial clear cell carcinoma.

    PubMed

    Fadare, Oluwole; Liang, Sharon X

    2012-12-01

    Hepatocyte nuclear factor 1-beta (HNF1β) has recently emerged as a relatively sensitive and specific marker for ovarian clear cell carcinoma. The purpose of this study is to assess the diagnostic utility of this marker for endometrial clear cell carcinoma. Immunohistochemical analysis was performed on 75 endometrial tissues using a goat polyclonal antibody raised against a peptide mapping at the C-terminus of human HNF1β protein. The 75 cases included 15 clear cell carcinomas, 20 endometrioid carcinomas, 15 endometrial serous carcinomas/uterine papillary serous carcinomas, 20 cases of normal endometrium, 2 cases of clear cell metaplasia, and 3 cases of Arias Stella reaction. Staining interpretations were based on a semiquantitative scoring system, a 0 to 12+ continuous numerical scale that was derived by multiplying the extent of staining (0 to 4+ scale) by the intensity of staining (0 to 3+ scale) for each case. HNF1β expression was found to be present in a wide spectrum of tissues. Twenty-seven (54%) of the 50 carcinomas displayed at least focal nuclear HNF1β expression, including 11 (73%) of 15, 9 (60%) of 15, and 7 (35%) of 20 clear cell, serous, and endometrioid carcinomas, respectively. The average nuclear staining scores for clear cell carcinomas, endometrioid carcinomas, and serous carcinomas were 5.2, 1.4, and 4.1, respectively. Clear cell carcinomas and endometrioid carcinomas displayed statistically significant differences regarding their nuclear staining scores (P = 0.0027), but clear cell carcinomas and endometrial serous carcinomas did not (P = 0.45). The calculated sensitivity of any nuclear HNF1β expression in classifying a carcinoma as being of the clear cell histotype was 73%, whereas the specificity was 54%. Nineteen of 20 normal endometrium samples displayed at least focal nuclear expression of HNF1β, and this expression was often diffuse. The 5 cases of benign histologic mimics of clear cell carcinomas (Arias Stella reaction and clear

  4. Comparison of Risk Factors and survival of Type 1 and Type II Endometrial Cancers

    PubMed Central

    Malik, Tahira Y.; Chishti, Uzma; Aziz, Aliya B.; Sheikh, Irfan

    2016-01-01

    Objective: To compare risk factors and progression free survival of type 1 & 2 endometrial cancers. Methods: A retrospective analysis of 149 patients with early stage endometrial carcinoma treated between 1997 and 2012 in Aga Khan University Hospital, Karachi was performed. Results: A total of 149 patients were analyzed. Type I tumors accounted for 92% of cases in the study while 8% were type II tumors. The mean age, BMI, parity, co-morbidities (hypertension & Diabetes), family history and history of polycystic disease were comparable in both groups. Overall better survival (113 Vs 24 months) was observed for type I endometrial cancer. Conclusion: Both types of endometrial cancer may share common etiologic factors. Despite the limitation of small numbers in one group this study confirms better survival in type 1 endometrial cancer. PMID:27648033

  5. MMAC/PTEN gene expression in endometrial cancer: RT-PCR studies.

    PubMed

    Sobczuk, Anna; Smolarz, Beata; Romanowicz-Makowska, Hanna; Pertyński, Tomasz

    2006-01-01

    Mutations in the MMAC/PTEN (phosphatase and tensin homologue deleted on chromosome 10) gene are documented in cancers of the breast, prostate, ovary, colon, melanoma, glioblastoma, lymphoma and endometrium. In the present work MMAC/PTEN gene expression in women with endometrial adenocarcinoma (n=70) in RNA samples obtained from cancer tissue were investigated. Control DNA was obtained from 68 normal endometrial tissue. The MMAC/PTEN expression was determined by RT-PCR analysis. The expression of MMAC/PTEN gene in endometrial adenocarcinoma cases was significantly reduced compared to the expression in the normal samples (P < 0.05). Furthermore the significant difference (P < 0.05) was observed between the expression of MMAC/PTEN in stage III versus lower stages of endometrial cancer. The results support the hypothesis that the MMAC/PTEN gene expression may be associated with the incidence of endometrial cancer.

  6. Two methods for establishing primary human endometrial stromal cells from hysterectomy specimens.

    PubMed

    Jividen, Kasey; Movassagh, Mercedeh Javanbakht; Jazaeri, Amir; Li, Hui

    2014-01-01

    Many efforts have been devoted to establish in vitro cell culture systems. These systems are designed to model a vast number of in vivo processes. Cell culture systems arising from human endometrial samples are no exception. Applications range from normal cyclic physiological processes to endometrial pathologies such as gynecological cancers, infectious diseases, and reproductive deficiencies. Here, we provide two methods for establishing primary endometrial stromal cells from surgically resected endometrial hysterectomy specimens. The first method is referred to as "the scraping method" and incorporates mechanical scraping using surgical or razor blades whereas the second method is termed "the trypsin method." This latter method uses the enzymatic activity of trypsin to promote the separation of cells and primary cell outgrowth. We illustrate step-by-step methodology through digital images and microscopy. We also provide examples for validating endometrial stromal cell lines via quantitative real time polymerase chain reactions (qPCR) and immunofluorescence (IF). PMID:24894444

  7. Human Endometrial Side Population Cells Exhibit Genotypic, Phenotypic and Functional Features of Somatic Stem Cells

    PubMed Central

    Cervelló, Irene; Gil-Sanchis, Claudia; Mas, Aymara; Delgado-Rosas, Francisco; Martínez-Conejero, José Antonio; Galán, Amparo; Martínez-Romero, Alicia; Martínez, Sebastian; Navarro, Ismael; Ferro, Jaime; Horcajadas, José Antonio; Esteban, Francisco José; O'Connor, José Enrique; Pellicer, Antonio; Simón, Carlos

    2010-01-01

    During reproductive life, the human endometrium undergoes around 480 cycles of growth, breakdown and regeneration should pregnancy not be achieved. This outstanding regenerative capacity is the basis for women's cycling and its dysfunction may be involved in the etiology of pathological disorders. Therefore, the human endometrial tissue must rely on a remarkable endometrial somatic stem cells (SSC) population. Here we explore the hypothesis that human endometrial side population (SP) cells correspond to somatic stem cells. We isolated, identified and characterized the SP corresponding to the stromal and epithelial compartments using endometrial SP genes signature, immunophenotyping and characteristic telomerase pattern. We analyzed the clonogenic activity of SP cells under hypoxic conditions and the differentiation capacity in vitro to adipogenic and osteogenic lineages. Finally, we demonstrated the functional capability of endometrial SP to develop human endometrium after subcutaneous injection in NOD-SCID mice. Briefly, SP cells of human endometrium from epithelial and stromal compartments display genotypic, phenotypic and functional features of SSC. PMID:20585575

  8. Comparison of Risk Factors and survival of Type 1 and Type II Endometrial Cancers

    PubMed Central

    Malik, Tahira Y.; Chishti, Uzma; Aziz, Aliya B.; Sheikh, Irfan

    2016-01-01

    Objective: To compare risk factors and progression free survival of type 1 & 2 endometrial cancers. Methods: A retrospective analysis of 149 patients with early stage endometrial carcinoma treated between 1997 and 2012 in Aga Khan University Hospital, Karachi was performed. Results: A total of 149 patients were analyzed. Type I tumors accounted for 92% of cases in the study while 8% were type II tumors. The mean age, BMI, parity, co-morbidities (hypertension & Diabetes), family history and history of polycystic disease were comparable in both groups. Overall better survival (113 Vs 24 months) was observed for type I endometrial cancer. Conclusion: Both types of endometrial cancer may share common etiologic factors. Despite the limitation of small numbers in one group this study confirms better survival in type 1 endometrial cancer.

  9. 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

    2016-10-27

    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

  10. Body Mass Index Is Positively Associated with Endometrial Cancer in Chinese Women, Especially Prior to Menopause

    PubMed Central

    Gao, Yifei; Dai, Xujing; Chen, Limei; Lee, Arier C; Tong, Mancy; Wise, Michelle; Chen, Qi

    2016-01-01

    Objective: Obesity is a well-known risk factor for developing endometrial cancer. However, the incidence and survival rate of endometrial cancer are associated with ethnicity and geographical area. In addition, whether menopausal status is associated with developing endometrial cancer in obese women and whether obesity is associated with subtypes of endometrial cancer have not been fully investigated. Here, we investigated the effect of BMI on developing endometrial cancer in Chinese women taking into account menopausal status and cancer subtypes. Methods: Data on 1,127 women with endometrial cancer including body mass index (BMI), age at diagnosis, parity, menopausal status and cancer subtype were collected from the largest obstetrics & gynaecology hospital in China and analysed. Results: After adjusting for age and parity, the odds for developing endometrial cancer in overweight or obese perimenopausal women was significantly higher than that in women with normal weight (OR=2.6 with 95%CI:1.9-3.5, and OR=3.5 with 95%CI: 2.2-5.4, respectively). The odds of developing endometrial cancer in overweight postmenopausal women were significantly higher than that in women who were normal weight (OR=2.4 with 95%CI: 1.8-3.1), however this was not the case for obese postmenopausal women. We further found that BMI, menopausal status, age and parity were not associated with subtypes of endometrial cancer. Conclusion: Our data demonstrate that obesity is positively associated with the incidence of developing endometrial cancer in Chinese women, with more significant effects in perimenopausal women. PMID:27326261

  11. Quantifying nonverbal communicative behavior in face-to-face human dialogues

    NASA Astrophysics Data System (ADS)

    Skhiri, Mustapha; Cerrato, Loredana

    2002-11-01

    The referred study is based on the assumption that understanding how humans use nonverbal behavior in dialogues can be very useful in the design of more natural-looking animated talking heads. The goal of the study is twofold: (1) to explore how people use specific facial expressions and head movements to serve important dialogue functions, and (2) to show evidence that it is possible to measure and quantify the entity of these movements with the Qualisys MacReflex motion tracking system. Naturally elicited dialogues between humans have been analyzed with focus on the attention on those nonverbal behaviors that serve the very relevant functions of regulating the conversational flux (i.e., turn taking) and producing information about the state of communication (i.e., feedback). The results show that eyebrow raising, head nods, and head shakes are typical signals involved during the exchange of speaking turns, as well as in the production and elicitation of feedback. These movements can be easily measured and quantified, and this measure can be implemented in animated talking heads.

  12. 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...

  13. Dialogue, Volume 3 Nos. 1-4, December 1985-December 1986.

    ERIC Educational Resources Information Center

    Staton, Jana, Ed.; And Others

    1986-01-01

    These four issues of a bulletin on the use of dialogue journals in foreign language teaching include these articles: "Dialogue Journals and Reading Comprehension"; "Secret Messages: Dialogue Journals as a Reading Event"; "The Teacher's Writing as Text"; "Using Dialogue Journals in Reading Classes"; "Effective Teacher Change: A Focus on the…

  14. 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.

  15. 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

  16. HIF-1α and GLUT-1 Expression in Atypical Endometrial Hyperplasia, Type I and II Endometrial Carcinoma: A Potential Role in Pathogenesis

    PubMed Central

    Abdou, Asmaa Gaber; Wahed, Moshira Mohammed Abdel; Kassem, Hend Abdou

    2016-01-01

    Introduction Hypoxia-Inducible Factor 1α (HIF-1α) is one of the major adaptive responses to hypoxia, regulating the activity of glucose transporter -1 (GLUT-1), responsible for glucose uptake. Aim To evaluate the immunohistochemical expression of both HIF-1α and GLUT-1 in type I and II endometrial carcinoma and their correlation with the available clinicopathologic variables in each type. Materials and Methods A retrospective study was conducted on archival blocks diagnosed from pathology department between April 2010 and August 2014 included 9 cases of atypical hyperplasia and 67 cases of endometrial carcinoma. Evaluation of both HIF-1α and GLUT-1 expression using standard immunohistochemical techniques performed on cut sections from selected paraffin embedded blocks. Statistical Analysis Descriptive analysis of the variables and statistical significances were calculated by non-parametric chi-square test using the Statistical Package for the Social Sciences version 12.0 (SPSS). Results HIF-1α was expressed in epithelial (88.9%, 52.2%, 61.2% and 50%) and stromal (33.3%, 74.6%. 71.4% and 83.3%) components of hyperplasia, total cases of EC, type I and II EC, respectively. GLUT-1 was expressed in the epithelial component of 88.9%, 98.5%, 98% and 100% of hyperplasia, total EC cases, type I and II EC, respectively. The necrosis related pattern of epithelial HIF-1α expression was in favour of type II (p=0.018) and grade III (p=0.038). HIF-1α H-score was associated with high apoptosis in both type I and total cases of EC (p=0.04). GLUT-1 H-score was negatively correlated with apoptotic count (p=0.04) and associated with high grade (p=0.003) and advanced stage in total EC (p=0.004). GLUT-1 H-score was correlated with the pattern of HIF-1α staining in all cases of EC (p= 0.04). Conclusion The role of HIF-1α in epithelial cells may differ from that of stromal cells in EC; however they augment the expression of each other supporting the crosstalk between them. The

  17. Lifetime physical activity and risk of endometrial cancer

    PubMed Central

    John, Esther M.; Koo, Jocelyn; Horn-Ross, Pamela L.

    2010-01-01

    Background The role of moderate physical activity and life patterns of activity in reducing endometrial cancer risk remains uncertain. Methods We assessed lifetime histories of activity from recreation, transportation, chores, and occupation and other risk factors in a population-based case-control study of endometrial cancer conducted in the San Francisco Bay area. The analysis was based on 472 newly diagnosed cases ascertained by the regional cancer registry and 443 controls identified by random-digit dialing who completed an in-person interview. Results Reduced risks associated with greater lifetime physical activity (highest vs. lowest tertile) were found for both total activity (odds ratio (OR) = 0.61 (95% confidence interval (CI) = 0.43–0.87, ptrend = 0.01) and activity of moderate intensity (OR=0.44, 95% CI=0.30–0.64, ptrend < 0.0001). Compared to women with low lifetime physical activity (below median), those with greater activity throughout life had the highest reduction in risk (OR=0.62, 95% CI=0.44–0.88). Inverse associations were stronger in obese and overweight women, but differences were not statistically significantly different from those in normal weight women. Conclusion These findings suggest that physical activity in adulthood, even of moderate intensity, may be effective in lowering the risk of endometrial cancer, particularly among those at highest risk for this disease. Impact The results emphasize the importance of evaluating lifetime histories of physical activity from multiple sources, including both recreational and non-recreational activities of various intensities, in order to fully understand the relation between physical activity and disease risk. PMID:20406960

  18. Transvaginal ultrasound examination of myometrial infiltration by endometrial cancer.

    PubMed

    Miklos, P; Klacko, M; Babala, P; Masak, L; Ondrus, D; Waczulikova, I

    2014-01-01

    The depth of myometrial infiltration by endometrial cancer is an important prognostic factor. The examination of the depth of infiltration classifies the patients in the low- and high-risk groups, which influences the therapeutic approach. Transvaginal ultrasonography represents a first-choice diagnostic test for the assessment of the depth of myometrial infiltration as the time consumption and financial demands of magnetic resonance imaging need to be taken into account. In comparison with the MRI, the diagnostic accuracy of the transvaginal ultrasound depends more on the individual experience and professional potential of the examining physician. This fact can contribute to the heterogeneity of published results of transvaginal ultrasound on the determination of infiltration depth. Having in mind the aim to verify these indicators in our local conditions and environment, we decided to prospectively study 150 endometrial cancer patients who were examined with the transvaginal ultrasound in the period 1/2009 - 10/ 2011. Correlated firstly with the preoperative and then secondly with the definitive histopathological examination was the depth-of-infiltration-related data that had been taken from the ultrasound findings. The output being monitored was the exclusion or confirmation of the invasion exceeding half the thickness of myometrium. In our study, the diagnostic accuracy of the method reached 82.67 %, while the other indicators were as follows: sensitivity 92.31 %, specificity 79.28 %, positive predictive value (PPV) 61.02 %, negative predictive value (NPV) 96.7 %, the likelihood ratio of a positive test 4.455 and the likelihood ratio of a negative test 0.097. The results of the depth of myometrial infiltration examination and their comparison with the data from similarly oriented clinical studies entitle us to include this examination in the set of standard preoperative methods used for the examination of patients with endometrial cancer (Tab. 3, Fig. 5, Ref

  19. 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

  20. 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.

  1. 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

  2. Endometrial decidualization: a rare cause of acute appendicitis during pregnancy

    PubMed Central

    Murphy, Skyle J.; Kaur, Anupinder; Wullschleger, Martin E.

    2016-01-01

    Appendicular endometriosis is a rare and poorly understood pathology that affects women in their reproductive years. In the gravid woman, ectopic endometrial tissue undergoes decidualization. This physiological process can result in acute appendicitis in exceptional cases. Here we describe a patient in her second trimester of pregnancy who presented with right iliac fossa pain and clinical, laboratory and imaging findings consistent with acute appendicitis. A laparoscopic appendectomy was performed with intraoperative findings suspicious for malignancy. Histological analysis made the surprising diagnosis of decidualized endometriosis causing luminal constriction resulting in acute appendicitis. We also detail the challenging diagnostic and management issues faced by clinicians in such cases. PMID:27106612

  3. 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.

  4. 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)

  5. 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.

  6. Dialogue and Inquiring Systems: The Development of a Social Logic

    ERIC Educational Resources Information Center

    Freedle, Roy

    1975-01-01

    Two aspects of dialectical psychology are considered: the synthesis of a larger cognitive system from two previously separate parent systems, and a demonstration of how and why dialogue undergoes continual change with occasional eruptions of logical contradictions. (JMB)

  7. 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

  8. The role of glycogen synthase kinase-3β (GSK-3β) in endometrial carcinoma: A carcinogenesis, progression, prognosis, and target therapy marker

    PubMed Central

    Chen, Shuo; Sun, Kai-Xuan; Liu, Bo-Liang; Zong, Zhi-Hong; Zhao, Yang

    2016-01-01

    Purpose Glycogen synthase kinase-3β (GSK-3β) is a serine/threonine kinase involved in cancer development. Herein, we demonstrated the role of GSK-3β in endometrial cancer (EC) and identified new therapeutic targets. Results GSK-3β was overexpressed in EC tissues, and was positively correlated with International Federation of Gynecology and Obstetrics (FIGO) staging, dedifferentiation, and myometrial infiltration depth. Besides, GSK-3β overexpression predicted lower cumulative and relapse-free survival rate. si-GSK-3β transfection suppressed cell proliferation, migration, invasion, and promoted cell apoptosis through downregulating NF-kB, Cyclin D1 and MMP9 expression whereas upregulating P21 expression. Bioinformatic predictions and dual-luciferase reporter assays showed that GSK-3β was a possible target of miR-129. MiR-129 transfection reduced GSK-3β expression, and exhibited the same trend as si-GSK-3β transfection in cell function experiments. The nude mouse xenograft assay showed that miR-129 overexpression may suppress tumor growth through downregulating GSK-3β expression. Further studies showed that AZD1080, a GSK-3β inhibitor, could also inhibit EC cell proliferation, migration and invasion, while induced cell apoptosis through modulating relevant genes downstream of GSK-3β signaling. Experimental Design GSK-3β expression was determined in EC tissue and normal endometrial tissues by immunohistochemistry. After GSK-3β down-regulation by si-GSK-3β, microRNA-129 mimic transfection or GSK-3β inhibitor exposure, EC cell phenotypes and related molecules were examined. Conclusions Our results demonstrate for the first time that GSK-3β may be a novel and important therapeutic target for the treatment of endometrial carcinoma. GSK-3β inhibitor AZD1080 may be an effective drug for treating endometrial carcinoma. PMID:27050373

  9. 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

    2016-09-19

    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

  10. Fibulin-5 is upregulated in decidualized human endometrial stromal cells and promotes primary human extravillous trophoblast outgrowth.

    PubMed

    Winship, Amy; Cuman, Carly; Rainczuk, Katarzyna; Dimitriadis, Evdokia

    2015-12-01

    Interactions between the highly invasive trophoblasts and the maternal uterine decidual extracellular matrix (ECM) are crucial in the determination of a successful pregnancy. Fibulin-5 (FBLN5) is a member of the fibulin family that alters cell adhesive and invasive properties and is expressed in human villous cytotrophoblasts. We aimed to determine the expression and immunolocalization of FBLN5 in human first trimester decidua and examine the effect of FBLN5 in trophoblast invasion in vitro using a first trimester placental villous outgrowth assay. We demonstrated that FBLN5 mRNA expression is upregulated in response to cAMP-mediated decidualization of primary human endometrial stromal cells, although FBLN5 itself does not enhance decidualization. We reported for the first time, FBLN5 protein production in first trimester decidual cells and also co-localization to HLAG-positive EVTs in first trimester decidua. Consequently, we investigated the effects of exogenous FBLN5 on placental villous outgrowth in vitro and demonstrated that FBLN5 promotes EVT migration/invasion. This is the first study to identify FBLN5 in decidualized human endometrial stromal cells, first trimester decidua and EVT and determine a functional role for FBLN5 in human EVTs, suggesting that decidual and or EVT-derived FBLN5 regulates EVT invasion and placentation in women. PMID:26506560

  11. S100A1 Expression in Ovarian and Endometrial Endometrioid Carcinomas Is a Prognostic Indicator of Relapse-Free Survival

    PubMed Central

    DeRycke, Melissa S.; Andersen, John D.; Harrington, Katherine M.; Pambuccian, Stefan E.; Kalloger, Steve E.; Boylan, Kristin L.M.; Argenta, Peter A.; Skubitz, Amy P.N.

    2011-01-01

    We sought to investigate the expression levels of S100A1 in ovarian cancer cell lines and tissues to correlate S100A1 with subtype, stage, grade, and relapse-free survival. S100A1 messenger RNA and protein were up-regulated in ovarian cancer cell lines and tumors compared with normal ovarian cell lines and tissues by gene microarray analysis, reverse transcriptase–polymerase chain reaction, quantitative reverse transcriptase–polymerase chain reaction, and Western immunoblotting. In the study, 63.7% of serous, 21.2% of clear cell, 11.2% of endometrioid, and 3% of mucinous ovarian (1/31) cancers were S100A1+ by immunohistochemical staining of tissue microarrays (n = 500). S100A1 expression increased with increasing Silverberg grade but not stage in serous tumors. Endometrial tissue microarrays (n = 127) were 9.4% S100A1+; no correlation with stage or grade and S100A1 was found. In the endometrioid subtype of ovarian and endometrial cancers, relapse-free survival was decreased for patients with S100A1+ tumors. These data suggest that S100A1 is a marker for poor prognosis of endometrioid subtypes of cancer. PMID:19926575

  12. Reflections on the dialogue process, FRAME and the Three Rs.

    PubMed

    Smith, Jane A

    2009-12-01

    My contribution to FRAME's 40th Anniversary meeting started by looking back: offering some reflections on the benefits and difficulties of engaging in wide-ranging dialogue on laboratory animal issues, largely based on experience with two forums - both of which have involved FRAME. Drawing on this discussion, I then looked forward: arguing that such dialogue now has an especially important role to play in developing strategies to replace (and reduce or avoid) the use of animals in research. PMID:20105014

  13. Endometrial and cervical cancer: incidence and mortality among women in the Lodz region

    PubMed Central

    Leśniczak, Beata; Krasomski, Grzegorz; Oszukowski, Przemysław; Woźniak, Piotr

    2015-01-01

    Introduction By the early 21st century the most common cancer of female genitals in Poland was cervical cancer. Now endometrial cancer ranks first. The aim of this study was to analyse the incidence and mortality of endometrial and cervical cancer among women in the Lodz region. Material and methods Data on the incidence and mortality of endometrial and cervical cancer among inhabitants of the Lodz region were obtained from the National Cancer Registry and Bulletin of Cancer Cases in the Lodz region. The analysis covered ten consecutive years beginning in 2001. Results The number of new cases reported in 2010 exceeded that observed in 2001 by 181. The standardized incidence rate of endometrial cancer increased by 6.3, while the standardized incidence rate of cervical cancer decreased by 1.4. Conclusions In the years 2001-2010, the incidence of endometrial cancer increased by 88.3% and that of cervical cancer decreased by 6.5% among inhabitants of the Lodz region. In the years 2001-2010, mortality of endometrial cancer increased by 24.5% and that of cervical cancer decreased by 12.6%. In 2010, the highest crude incidence rates in the Lodz region of both endometrial and cervical cancer at 39.1 were recorded in the district town of Piotrków. PMID:26528109

  14. Joint Effect of Genotypic and Phenotypic Features of Reproductive Factors on Endometrial Cancer Risk

    PubMed Central

    Wang, Zhanwei; Risch, Harvey; Lu, Lingeng; Irwin, Melinda L.; Mayne, Susan; Schwartz, Peter; Rutherford, Thomas; De Vivo, Immaculata; Yu, Herbert

    2015-01-01

    Prolonged estrogen exposure is believed to be the major cause of endometrial cancer. As possible markers of estrogen exposure, various menstrual and reproductive features, e.g., ages at menarche and menopause, are found to be associated with endometrial cancer risk. In order to assess their combined effects on endometrial cancer, we created the total number of menstrual cycles (TNMC) that a woman experienced during her life or up to the time of study and two genetic risk scores, GRS1 for age at menarche and GRS2 for age at menopause. Comparing 482 endometrial cancer patients with 571 population controls, we found TNMC was associated with endometrial cancer risk and that the association remained statistically significant after adjustment for obesity and other potential confounders. Risk increased by about 2.5% for every additional 10 menstrual-cycles. The study also showed that high GRS1 was associated with increased risk. This relationship, however, was attenuated after adjustment for obesity. Our study further indicated women with high TNMC and GRS1 had twice the risk of endometrial cancer compared to those low in both indices. Our results provided additional support to the involvement of estrogen exposure in endometrial cancer risk with regard to genetic background and lifestyle features. PMID:26498156

  15. Genetic imbalances in precursor lesions of endometrial cancer detected by comparative genomic hybridization.

    PubMed

    Kiechle, M; Hinrichs, M; Jacobsen, A; Lüttges, J; Pfisterer, J; Kommoss, F; Arnold, N

    2000-06-01

    Endometrial hyperplasia is regarded as a precursor lesion of endometrioid adenocarcinomas of the endometrium. The genetic events involved in the multistep process from normal endometrial glandular tissue to invasive endometrial carcinomas are primarily unknown. We chose endometrial hyperplasia as a model for identifying chromosomal aberrations occurring during carcinogenesis. Comparative genomic hybridization (CGH) was performed on 47 formalin-fixed, paraffin-embedded specimens of endometrial hyperplasia using the microdissection technique to increase the number of tumor cells in the samples and reduce contamination from normal cells. CGH analysis revealed that 24 out of 47 (51%) samples had detectable chromosomal imbalances, whereas 23 (49%) were in a genetically balanced state. The incidence of aberrant CGH profiles tended to parallel dysplasia grade, ranging from 22% aberrant profiles in simple hyperplasia to 67% in complex hyperplasia with atypia. The most frequent imbalances were 1p, 16p, and 20q underrepresentations and 4q overrepresentations. Copy number changes in 1p were more frequent in atypical complex hyperplasia than in complex lesions without atypical cells or simple lesions (42% versus 20% and 0%). Our results show that endometrial hyperplasia reveals recurrent chromosomal imbalances which tend to increase with the presence of atypical cells. The most frequent aberrations in endometrial cancer, 1q and 8q overrepresentations, are not present or are rare in its precursor lesions. This analysis provides evidence that tumorigenesis proceeds through the accumulation of a series of genetic alterations and suggests a stepwise mode of tumorigenesis. PMID:10854205

  16. Cyto-histologic evaluation of the endometrium in climacteric women at risk for endometrial carcinoma.

    PubMed

    de Aloysio, D; Rocca, G; Miliffi, L

    1986-08-31

    The authors evaluated the diagnostic effectiveness of a triple specimen technique (cyto-histologic) performed by the Perma device. The incidence of endometrial hyperplasia (according to Dallenbach-Hellweg's classification) was estimated in 254 climacteric women selected from outpatients who come spontaneously to the Menopause Clinic of the Obstetrics and Gynecology Department (Bologna University). The selection criterion was the evidence of risk factors for endometrial carcinoma, climacteric bleedings (obesity, late menopause, high blood pressure, diabetes), or endometriotropic estrogen therapy in the postmenopause. Results showed that the cyto-histologic sampling is most useful for diagnosing endometrial hyperplasia and early carcinoma (diagnostic effectiveness: 89.0-93.8%). Also, endometrial hyperplasia was found to have a significant incidence in the group we examined. This incidence was highest in women with climacteric bleedings, secondly in women using high-dose estrogens, and thirdly in women with risk factors for endometrial carcinoma. When evaluating the different kinds of endometrial hyperplasia, we never found adenomatous hyperplasia in women on estrogen therapy. Affinity between histologic and cytologic classes was around 50% in endometrial hyperplasia and 100% in early carcinoma. This emphasizes that both samplings are needed to perform an accurate diagnosis.

  17. Factors Influencing the Recurrence Potential of Benign Endometrial Polyps after Hysteroscopic Polypectomy

    PubMed Central

    Yang, Jehn-Hsiahn; Chen, Chin-Der; Chen, Shee-Uan; Yang, Yu-Shih; Chen, Mei-Jou

    2015-01-01

    Background An endometrial polyp is a frequently encountered gynecologic disease with abnormal uterine bleeding and infertility being the two common presenting problems, and hysteroscopic polypectomy is an effective method to remove them. The postoperative polyp recurrence might result in reappearance of abnormal uterine bleeding or infertility, whereas factors influencing the postoperative recurrence potential have limited data. Methods This case-series report included 168 premenopausal women who suffered from endometrial polyps and underwent hysteroscopic polypectomy. All of them were awaiting a future pregnancy. Office hysteroscopy was done before and after hysteroscopic polypectomy, in which preoperative hysteroscopy examined the number, type, and location of endometrial polyps, and postoperative hysteroscopy checked the polyp recurrence. Surgical indications, either infertility or the presentation of abnormal uterine bleeding, and follow-up duration were recorded. Results Seventy-three out of 168 (43%) women had polyp recurrence after hysteroscopic polypectomy. Multivariate logistic regression analysis revealed that more endometrial polyps (P = 0.015) and longer duration of follow-up (P = 0.004) were significantly associated with an increased risk of postoperative polyp recurrence. The type of endometrial polyps was not correlated with polyp recurrence potential, whereas pedunculated type endometrial polyps were closely related to the presentation of abnormal uterine bleeding (P = 0.001). Conclusions A higher number of endometrial polyps and longer follow-up duration are associated with a greater potential of polyp recurrence after hysteroscopic polypectomy. PMID:26660149

  18. Malignant and premalignant changes in the endometrium of women with an ultrasound diagnosis of endometrial polyp.

    PubMed

    Gambadauro, P; Martínez-Maestre, M Á; Schneider, J; Torrejón, R

    2014-10-01

    The association between polyps and endometrial cancer is under debate. The main objectives of this study were to study the frequency and the characteristics of malignant and premalignant endometrial changes in women with endometrial polyp at ultrasound. The study population consisted of 1,390 consecutive patients that were referred to office hysteroscopy because of the ultrasonographic diagnosis of endometrial polyps. A total of 16 cases of endometrial neoplasia were diagnosed (1.15%). The frequencies of atypia and cancer in our population were 0.14% and 1.01%, respectively. All patients, except one, were postmenopausal (93.8%). All had undergone the initial ultrasonographic assessment because of symptoms (bleeding in the 93.8%). The neoplasia was not confined to the polyp in 75% of the cases. Nine cases had a lower risk disease (56.25%; atypical hyperplasia or endometrial cancer stage IA-G1,2), while seven had a higher risk cancer (43.75%; ≥ stage IA-G3). Patients with a higher risk disease were found to be significantly younger, and their polyps were smaller, albeit non-significantly. In spite of the common practice to refer all women with an ultrasound diagnosis of polyp to hysteroscopy, our data show how the prevalence of endometrial neoplasia in these patients is low (1.15%). Moreover, the malignancy is not confined to a polyp in most of the cases.

  19. 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.

  20. Association of leukocyte telomere length in peripheral blood leukocytes with endometrial cancer risk in Caucasian Americans.

    PubMed

    Sun, Yuhui; Zhang, Liren; Zhao, Lina; Wu, Xifeng; Gu, Jian

    2015-11-01

    Telomeres are the protective structure at the ends of each chromosome and play an important role in maintaining genomic integrity. Interindividual variation of telomere length in peripheral blood leukocytes has been associated with the risks of developing many human diseases including several cancers. The association between leukocyte telomere length (LTL) and endometrial cancer risk is still inconsistent. Using a case-control study of endometrial cancer patients (n = 139) and control subjects (n = 139) in a Caucasian population, we assessed the association of relative LTL with the risk of endometrial cancer. We calculated odds ratios and 95% confidence intervals using multivariate logistic regression. We also determined the joint effects of LTL with established risk factors of endometrial cancer. The normalized LTL was significantly longer in endometrial cancer cases (median, 0.93; range, 0.19-1.62) than in controls (median, 0.70; range, 0.03-2.14) (P < 0.001). When individuals were dichotomized into long and short groups based on the median LTL value in the controls, individuals with long LTL had a significantly increased risk of endometrial cancer (adjusted OR, 3.84; 95%CI, 2.16-6.85; P < 0.001) compared to those with short LTL. When individuals were categorized into three groups or four groups according to tertile or quartile LTL value in the controls, there was a significant dose-response association between LTL and the risk of endometrial cancer (P < 0.001). Joint effects between LTL and smoking status, body mass index and a history of hypertension or diabetes in elevating endometrial cancer risk were observed. Long telomere length in peripheral blood leukocytes is associated with a significantly increased risk of endometrial cancer.

  1. The impact of low-volume uterine lavage on endometrial biopsy classification.

    PubMed

    Linton, J K; Sertich, P L

    2016-09-01

    In the mare, the low-volume uterine lavage technique allows for bacterial sampling of the entire uterine lumen and is usually performed after obtaining the traditional double-guarded endometrial swab for aerobic culture and cytology and before procurement of an endometrial biopsy sample during a breeding soundness examination. The purpose of this study was to explore the potential effects of the low-volume lavage on the endometrial biopsy classification and polymorphonuclear cell (PMNs) infiltration in the context of a breeding soundness examination. Fourteen light horse mares of mixed breed, age 7 to 21 years, with known reproductive history, were included in the study, matched by age and reproductive history, and then divided into treatment and control groups. Transrectal palpation and ultrasonography, endometrial swabbing, and the first endometrial biopsy were performed in all mares. Low-volume uterine lavage was performed in the treatment group but not the control group. After either the lavage or a 15-minute rest, a second endometrial biopsy was obtained from both the control and treatment groups. Endometrial swabs and effluent from the low-volume lavages were submitted for aerobic culture and sensitivity. Biopsy samples were fixed in Bouin's solution for 24 hours, processed, stained with hematoxylin and eosin, and then viewed under bright light microscopy. Additional staining with anti-neutrophil elastase antibody (ab68672) was performed for indirect immunohistochemistry. All samples were interpreted by a blinded observer. When the first (pre-uterine lavage) and second (post-uterine lavage) biopsies were compared using a mixed-effects logistic regression, there was no difference in endometrial biopsy classification (P = 0.74), presence of PMNs in blood vessels (P = 0.728), or infiltration of PMNs in the tissue (P = 0.934) between the treatment and control groups. In this study, the low-volume uterine lavage did not affect the endometrial biopsy

  2. 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

  3. Role of Liquid-based Cytology and Cell Block in the Diagnosis of Endometrial Lesions

    PubMed Central

    Zhang, Hui; Wen, Jia; Xu, Pi-Li; Chen, Rui; Yang, Xi; Zhou, Lian-Er; Jiang, Ping; Wan, An-Xia; Liao, Qin-Ping

    2016-01-01

    Background: Liquid-based cytology (LBC) offers an alternative method to biopsy in screening endometrial cancer. Cell block (CB), prepared by collecting residual cytological specimen, represents a novel method to supplement the diagnosis of endometrial cytology. This study aimed to compare the specimen adequacy and diagnostic accuracy of LBC and CB in the diagnosis of endometrial lesions. Methods: A total of 198 women with high risks of endometrial carcinoma (EC) from May 2014 to April 2015 were enrolled in this study. The cytological specimens were collected by the endometrial sampler (SAP-1) followed by histopathologic evaluation of dilatation and curettage or biopsy guided by hysteroscopy. The residual cytological specimens were processed into paraffin-embedded CB after LBC preparation. Diagnostic accuracies of LBC and CB for detecting endometrial lesions were correlated with histological diagnoses. Chi-square test was used to compare the specimen adequacies of LBC and CB. Results: The specimen inadequate rate of CB was significantly higher than that of LBC (22.2% versus 7.1%, P < 0.01). There were 144 cases with adequate specimens for LBC and CB preparation. Among them, 29 cases were atypical endometrial hyperplasia (11 cases) or carcinoma (18 cases) confirmed by histology evaluation. Taking atypical hyperplasia and carcinoma as positive, the diagnostic accuracy of CB was 95.1% while it was 93.8% in LBC. When combined LBC with CB, the diagnostic accuracy was improved to 95.8%, with a sensitivity of 89.7% and specificity of 97.4%. Conclusions: CB is a feasible and reproducible adjuvant method for screening endometrial lesions. A combination of CB and LBC can improve the diagnostic accuracy of endometrial lesions. PMID:27270542

  4. 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

  5. Immunohistochemical characterisation of molecular subtypes in endometrial cancer

    PubMed Central

    Łapińska-Szumczyk, Sylwia M; Supernat, Anna M; Majewska, Hanna I; Gulczyński, Jacek; Biernat, Wojciech; Wydra, Dariusz; Żaczek, Anna J

    2015-01-01

    Four molecular subtypes have lately been established in endometrial cancer basing on estrogen receptor (ER), progesterone receptor (PR) and HER2 status: ER+/PR+/HER2+, ER+/PR+/HER2-, ER-/PR-/HER2+ and ER-/PR-/HER2-. The subtypes have shown diversity in terms of prognosis, clinicopathological and molecular characteristics, with ER+/PR+/HER2- and ER-/PR-/HER2+ group exhibiting exceptionally benign and aggressive behavior, respectively. We have further characterized the subtypes in the context of pathways known to drive endometrial carcinogenesis: phosphatidylinositol 3-kinase (PI3K)-AKT pathway (ERBB/PI3K pathway), TP53 system, and the mismatch repair (MMR) mechanism. Analysis of tumor heterogeneity was also included. ER+/PR+/HER2+ was characterized by active ERBB/PI3K pathway occurring in 58% of cases. Subtype ER-/PR-/HER2+ was characterized by the most frequent TP53 mutations (83% of cases). Triple negative phenotype utterly lacked active ERBB/PI3K pathway. Analyzed major pathways rarely correlated with clinicopathologial data but mutated TP53 and retained MMR did correlate with shorter overall survival (both P<0.01). The presence of tumor heterogeneity was most frequent in ER-/PR-/HER2+ subtype (53% of all cases). The presented results further emphasize that the molecular subtype distinction, along with MMR and TP53 status, could be a useful diagnostic tool in guiding individualized therapy. PMID:26885170

  6. 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.

  7. Implantation in assisted reproduction: a look at endometrial receptivity.

    PubMed

    Fatemi, H M; Popovic-Todorovic, B

    2013-11-01

    Implantation failure in assisted reproduction is thought to be mainly due to impaired uterine receptivity. With normal uterine anatomy, changes in endocrine profile during ovarian stimulation and medical conditions of the mother (i.e. thrombophilia and abnormal immunological response) could result in a non-receptive endometrium. High oestradiol concentrations during ovarian stimulation lead to premature progesterone elevation, causing endometrial advancement and hampering implantation, which can be overcome by a freeze-all approach and embryo transfer in natural cycles or by milder stimulation protocols. Patients with recurrent implantation failure (RIF) should be tested for inherited and acquired thrombophilias. Each patient should be individually assessed and counselled regarding therapy with low-molecular-weight heparin (LMWH). Empirical treatment with LMWH, aspirin or corticosteroids is not effective for women with RIF who have negative thrombophilic tests. If thrombophilic tests are normal, patients should be tested for immunological causes. If human leukocyte antigen dissimilarity is proven, treatment with intravenous immunoglobulin might be beneficial. Preliminary observational studies using intralipid infusion in the presence of increased natural killer cytotoxic activity are interesting but the proposed rationale is controversial and randomized controlled trials are needed. Hysteroscopy and/or endometrial scratching in the cycle preceding ovarian stimulation should become standard for patients with RIF.

  8. Endometrial regenerative cells: a novel stem cell population.

    PubMed

    Meng, Xiaolong; Ichim, Thomas E; Zhong, Jie; Rogers, Andrea; Yin, Zhenglian; Jackson, James; Wang, Hao; Ge, Wei; Bogin, Vladimir; Chan, Kyle W; Thébaud, Bernard; Riordan, Neil H

    2007-01-01

    Angiogenesis is a critical component of the proliferative endometrial phase of the menstrual cycle. Thus, we hypothesized that a stem cell-like population exist and can be isolated from menstrual blood. Mononuclear cells collected from the menstrual blood contained a subpopulation of adherent cells which could be maintained in tissue culture for >68 doublings and retained expression of the markers CD9, CD29, CD41a, CD44, CD59, CD73, CD90 and CD105, without karyotypic abnormalities. Proliferative rate of the cells was significantly higher than control umbilical cord derived mesenchymal stem cells, with doubling occurring every 19.4 hours. These cells, which we termed "Endometrial Regenerative Cells" (ERC) were capable of differentiating into 9 lineages: cardiomyocytic, respiratory epithelial, neurocytic, myocytic, endothelial, pancreatic, hepatic, adipocytic, and osteogenic. Additionally, ERC produced MMP3, MMP10, GM-CSF, angiopoietin-2 and PDGF-BB at 10-100,000 fold higher levels than two control cord blood derived mesenchymal stem cell lines. Given the ease of extraction and pluripotency of this cell population, we propose ERC as a novel alternative to current stem cells sources. PMID:18005405

  9. ECGene: A Literature‐Based Knowledgebase of Endometrial Cancer Genes

    PubMed Central

    Liu, Yining; O'Mara, Tracy A

    2016-01-01

    ABSTRACT Endometrial cancer (EC) ranks as the sixth common cancer for women worldwide. To better distinguish cancer subtypes and identify effective early diagnostic biomarkers, we need improved understanding of the biological mechanisms associated with EC dysregulated genes. Although there is a wealth of clinical and molecular information relevant to EC in the literature, there has been no systematic summary of EC‐implicated genes. In this study, we developed a literature‐based database ECGene (Endometrial Cancer Gene database) with comprehensive annotations. ECGene features manual curation of 414 genes from thousands of publications, results from eight EC gene expression datasets, precomputation of coexpressed long noncoding RNAs, and an EC‐implicated gene interactome. In the current release, we generated and comprehensively annotated a list of 458 EC‐implicated genes. We found the top‐ranked EC‐implicated genes are frequently mutated in The Cancer Genome Atlas (TCGA) tumor samples. Furthermore, systematic analysis of coexpressed lncRNAs provided insight into the important roles of lncRNA in EC development. ECGene has a user‐friendly Web interface and is freely available at http://ecgene.bioinfo‐minzhao.org/. As the first literature‐based online resource for EC, ECGene serves as a useful gateway for researchers to explore EC genetics. PMID:26699919

  10. Enolase-1 is a therapeutic target in endometrial carcinoma

    PubMed Central

    Shu, Luyun; Wang, Lijing; Chen, YiYu; Fu, Qiaofen; Liu, Yan; Hua, Shengni; Fan, Yue; Liu, Yiyi; Deng, Xiaojie; Luo, Rongcheng; Mei, Zhong; Jiang, Qinping; Liu, Zhen

    2015-01-01

    ENO1 plays a paradoxical role in driving the pathogenesis of tumors. However, the clinical significance of ENO1 expression remains unclear and its function and modulatory mechanisms have never been reported in endometrial carcinoma (EC). In this study, ENO1 silencing significantly reduced cell glycolysis, proliferation, migration, and invasion in vitro, as well as tumorigenesis and metastasis in vivo by modulating p85 suppression. This in turn mediated inactivation of PI3K/AKT signaling and its downstream signals including glycolysis, cell cycle progression, and epithelial-mesenchymal transition (EMT)-associated genes. These effects on glycolysis and cell growth were not observed after ENO1 suppression in normal human endometrial epithelial cells (HEEC). Knocking down ENO1 could significantly enhance the sensitivity of EC cells to cisplatin (DDP) and markedly inhibited the growth of EC xenografts in vivo. In clinical samples, EC tissues exhibited higher expression levels of ENO1 mRNA and protein compared with normal endometrium tissues. Patients with higher ENO1 expression had a markedly shorter overall survival than patients with low ENO1 expression. We conclude that ENO1 favors carcinogenesis, representing a potential target for gene-based therapy. PMID:25951350

  11. Human malignant melanoma-derived progestagen-associated endometrial protein immunosuppresses T lymphocytes in vitro.

    PubMed

    Ren, Suping; Chai, Lina; Wang, Chunyan; Li, Changlan; Ren, Qiquan; Yang, Lihua; Wang, Fumei; Qiao, Zhixin; Li, Weijing; He, Min; Riker, Adam I; Han, Ying; Yu, Qun

    2015-01-01

    Progestagen-associated endometrial protein (PAEP) is a glycoprotein of the lipocalin family that acts as a negative regulator of T cell receptor-mediated activation. However, the function of tumor-derived PAEP on the human immune system in the tumor microenvironment is unknown. PAEP is highly expressed in intermediate and thick primary melanomas (Breslow's 2.5mm or greater) and metastatic melanomas, correlating with its expression in daughter cell lines established in vitro. The current study investigates the role of melanoma cell-secreted PAEP protein in regulating T cell function. Upon the enrichment of CD3+, CD4+ and CD8+ T cells from human peripheral blood mononuclear cells, each subset was then mixed with either melanoma-derived PAEP protein or PAEP-poor supernatant of gene-silenced tumor cells. IL-2 and IFN-γ secretion of CD4+ T cells significantly decreased with the addition of PAEP-rich supernatant. And the addition of PAEP-positive cell supernatant to activated lymphocytes significantly inhibited lymphocyte proliferation and cytotoxic T cell activity, while increasing lymphocyte apoptosis. Our result suggests that melanoma cell-secreted PAEP protein immunosuppresses the activation, proliferation and cytotoxicity of T lymphocytes, which might partially explain the mechanism of immune tolerance induced by melanoma cells within the tumor microenvironment. PMID:25785839

  12. 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

  13. The polio narratives: dialogues with FDR.

    PubMed

    Fairchild, A L

    2001-01-01

    As a group of accounts that span the decades from the mid-1940s to the present, the published polio narratives enable us to align their shifting perceptions of disability with social, cultural, and technological change. This paper identifies two distinct groups of narratives. Authors of the first group, writing between the mid-1930s and mid-1950s--a period of relative prosperity, conformity, and homogeneity--were uncomfortable with radical movements, diversity, and conflict; their narratives typically told of either full or substantial recovery. Beginning in the mid-1950s--the period of both McCarthy and the Civil Rights movement--a second wave of narratives begins to tell stories of partial to serious disability; typically, they reflect on a lifetime of coping with chronic disability. Both sets of narratives, however, represent a dialogue with Franklin Delano Roosevelt. Roosevelt himself, journalists, and the National Foundation for Infantile Paralysis all helped to create and promote a core polio narrative featuring FDR's triumph over disease and disability that would become a national myth. Yet while the early narratives reinforced the core elements of the Roosevelt myth, the later ones began to challenge them.

  14. Endometrial biopsy in the infertility investigation. The experience at two institutions.

    PubMed

    Wild, R A; Sanfilippo, J S; Toledo, A A

    1986-10-01

    The combined experience at two institutions was reviewed to evaluate endometrial biopsy and the prognosis for pregnancies affected by endometrial sampling during the cycle of conception. In the evaluation of 1,084 patients, 1,174 biopsies were performed. Twenty-seven endometrial biopsies were done during the cycle of conception, with spontaneous abortion occurring in six cases (22.2%). Multiple diagnoses were made (including luteal phase defects, endometritis and polyps), and interruption of pregnancy occurred. Several cases illustrate disturbing complications. Methods of minimizing pregnancy interruption and patient discomfort are available.

  15. Distinction of endometrial stromal sarcomas from 'hemangiopericytomatous' tumors using a panel of immunohistochemical stains.

    PubMed

    Bhargava, Rohit; Shia, Jinru; Hummer, Amanda J; Thaler, Howard T; Tornos, Carmen; Soslow, Robert A

    2005-01-01

    Endometrial stromal sarcomas are low-grade malignant tumors that may pose a diagnostic challenge, especially when they are present in an extrauterine site. Owing to the presence of an arborizing vasculature and cells with an undifferentiated appearance, endometrial stromal sarcomas can be confused with several soft-tissue neoplasms. We studied 17 endometrial stromal sarcomas, eight hemangiopericytomas, 14 solitary fibrous tumors, and 16 synovial sarcomas immunohistochemically, detecting the following antigens: CD10, estrogen receptor, progesterone receptor, bcl-2, CD34, smooth muscle antigen, epithelial membrane antigen and cytokeratin (AE1/AE3). Most endometrial stromal sarcomas stained positively for CD10 (16/17), estrogen receptor (17/17), progesterone receptor (15/17), and bcl-2 (17/17). Staining with antismooth muscle antigen was seen in 11 of 17 cases of endometrial stromal sarcoma, with more intense staining seen in areas showing smooth muscle differentiation. Staining with AE1/3 was seen in four of 17 endometrial stromal sarcomas, with two of the positive cases containing epithelioid cells. None of the endometrial stromal sarcomas expressed epithelial membrane antigen or CD34. More than half of the hemangiopericytomas (4/8) and solitary fibrous tumors (9/14) cases demonstrated CD10 expression either focally or in a patchy cytoplasmic and membranous pattern. Hemangiopericytomas, solitary fibrous tumors, and synovial sarcomas did not express estrogen receptor. Four of eight hemangiopericytomas and seven of 14 solitary fibrous tumors also showed patchy progesterone receptor expression. CD34 expression was identified in six of eight hemangiopericytomas and 13 of 14 solitary fibrous tumors, but we did not find expression of CD34 in synovial sarcoma. Differences between endometrial stromal sarcoma and other soft-tissue tumors were detected for all of the immunohistochemical markers (P<0.05), except anti-bcl-2 and AE1/3. Antibodies against CD10 mark a substantial

  16. 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. PMID:26597220

  17. 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.

  18. Endometrial adenocarcinoma: an analysis of treatment and outcome.

    PubMed

    Byrd, Louise M; Swindell, Richard; Webber-Rookes, Daniel; Hannon, R; Hunter, Robin D; Livsey, Jac; Davidson, Susan E

    2008-11-01

    This study aims to review the survival and morbidity in patients treated for endometrial cancer, at a single centre and analyses the effects of co-morbidity on these outcomes. Case notes of all patients referred to the Christie Hospital with endometrial carcinoma from January 1, 1993 to December 31, 1995 (n=499) were reviewed. Twenty patients presented with recurrence and were not included in this analysis. Three hundred and seventy-five patients had previously undergone a total abdominal hysterectomy and bilateral salpingoophorectomy (+/- pelvic lymphadenectomy). Of these, 175 received adjuvant external beam radiotherapy (XRT) only, 49 received XRT and brachytherapy, 30 received brachytherapy alone and 121 patients had no further therapy. One hundred and four patients were referred for primary treatment. Radical radiotherapy was administered to 63 patients who were unfit for surgery, with 10 of these receiving XRT + brachytherapy and 53 receiving brachytherapy alone. Thirteen patients received palliative XRT and 28 supportive care only. The overall 5-year survival for those treated radically was 73.3%. There was no significant survival difference between patients who underwent surgery and adjuvant radiotherapy, in whatever form (p=0.115). Patients who did not undergo surgery did less well as a group, although there was no significant survival difference between those treated with combination therapy or brachytherapy alone (p=0.33). Survival was significantly associated with FIGO stage, tumour grade, age (especially those >75 years) and co-morbidity (ACE-27 score). Late morbidity occurred in 46 patients, with severe toxicity affecting 12 (3.8%). Toxicity was associated with ACE-27 score (p=0.0019), treatment dose and modality, with 50% (n=6) of severe toxicity seen in patients receiving adjuvant XRT + ICT. These data demonstrate that survival in patients with endometrial carcinoma treated radically remains good, with the stage and grade of tumour being significant

  19. Restraint stress delays endometrial adaptive remodeling during mouse embryo implantation.

    PubMed

    Liu, Guanhui; Dong, Yulan; Wang, Zixu; Cao, Jing; Chen, Yaoxing

    2015-01-01

    In mice, previously, we showed that restraint stress reduces the number of embryo implantation sites in the endometrium. Here, we hypothesized that the uterine microenvironment is altered by restraint stress and consequently is suboptimal for embryo implantation. On embryonic day 1 (E1), 60 of 154 pregnant CD1 mice underwent restraint stress (4 h), repeated daily to E3, E5 or E7 (n = 10 mice per group). Restraint stress decreased food intake and suppressed body weight gain on E3, E5 and E7. Restraint stress decreased the actual and relative weight (percent body weight) of uterus and ovary on E5 (by 14.9%, p = 0.03; 16.1%, p = 0.004) and E7 (by 16.8%, p = 0.03; 20.0%, p = 0.01). Morphologically, restraint stress decreased relative endometrial area (by 8.94-18.8%, p = 0.003-0.021) and uterine gland area (by 30.6%, p < 0.01 on E3 and 44.5%, p < 0.01 on E5). Immunohistochemistry showed that restraint stress decreased microvessel density (by 12.9-70.5%, p < 0.01) and vascular endothelial growth factor expression (by 14.6-45.9%, p = 0.007-0.02). Restraint stress decreased by 32.4-39.8% (p = 0.002-0.01) the mean optical density ratio for proliferating cell nuclear antigen/terminal deoxynucleotidyl transferase dUTP nick end labeling. Methyl thiazolyl tetrazolium assay showed a dose-dependent decrease in proliferative activity of endometrial stromal cells (from 52 of 154 pregnant E5 control mice) incubated with H2O2 (100-1000 μM) in vitro. These findings supported the hypothesis that restraint stress negatively influences endometrial adaptive remodeling via an oxidative stress pathway, which resulted in fewer implantation sites.

  20. Endometrial adult/progenitor stem cells: pathogenetic theory and new antiangiogenic approach for endometriosis therapy.

    PubMed

    Pittatore, G; Moggio, A; Benedetto, C; Bussolati, B; Revelli, A

    2014-03-01

    The cyclical arrival of endometrial cells into the abdominal cavity through retrograde flux at menstruation represents the etiopathogenetic basis of endometriosis. The endometrium has peculiar regenerative properties linked to the presence of adult stem cells similar to mesenchymal stem cells (MSCs). Once in the abdominal cavity, these MSCs could proliferate, invade, and differentiate into endometrial cells, finally generating ectopic implants. As only differentiated endometrial cells, and not endometrial MSCs, possess steroid hormone receptors, MSCs could be responsible for the high rate of persistence/recurrence of the disease after hypoestrogenism-inducing therapies. Even angiogenesis promoted by MSCs could play an important role, as survival and proliferation of endometriotic tissue depend on the formation of new blood vessels. Inhibition of angiogenesis represents, in fact, a new, promising therapeutic approach for the disease. Further, medications directly targeting endometriosis MSCs could be effective, alone or in association with hormonal treatments, in increasing the success of medical treatment.

  1. Global Endometrial Ablation in the Presence of Essure® Microinserts

    PubMed Central

    Aldape, Diana; Chudnoff, Scott G; Levie, Mark D

    2013-01-01

    Abnormal uterine bleeding (AUB) affects 30% of women at some time during their reproductive years and is one of the most common reasons a woman sees a gynecologist. Many women are turning to endometrial ablation to manage their AUB. This article reviews the data relating to the available endometrial ablation techniques performed with hysteroscopic sterilization, and focuses on data from patients who had Essure® (Conceptus, San Carlos, CA) coils placed prior to performance of endometrial ablation. Reviewed specifically are data regarding safety and efficacy of these two procedures when combined. Data submitted to the US Food and Drug Administration for the three devices currently approved are reviewed, as well as all published case series. Articles included were selected based on a PubMed search for endometrial ablation (also using the brand names of the different techniques currently available), hysteroscopic sterilization, and Essure. PMID:24358407

  2. Circulating adiponectin levels and risk of endometrial cancer: Systematic review and meta-analysis

    PubMed Central

    LI, ZHI-JUN; YANG, XUE-LING; YAO, YAN; HAN, WEI-QING; LI, BO

    2016-01-01

    Previous epidemiological studies have presented conflicting results regarding associations between circulating adiponectin (APN) levels and the risk of endometrial cancer. Thus a meta-analysis was performed to investigate the association between these factors. Multiple electronic sources, including PubMed, SpringerLink and Google Scholar databases were searched to identify relevant studies for the present meta-analysis. All of the selected studies examined the correlation between circulating APN levels and endometrial cancer. The standardized mean difference (SMD) and 95% confidence intervals (CIs) were estimated and pooled using meta-analysis methods. Overall, 18 case-control studies met the inclusion criteria. A total of 5,692 participants and 2,337 cases of endometrial cancer were included in this meta-analysis. The SMD of the pooled analysis (95% CI) were −1.96 (−2.60, −1.31), P=0.000. When the cancer grades were compared, the APN values were not significantly different between the grades of endometrial cancer [G1 vs. G3, 1.02 (−0.68, 2.72), P>0.05; G1 vs. G2, 0.34 (−0.86, 1.54), P>0.05]. However, there was a significant association between high APN levels and postmenopausal endometrial cancer cases with an SMD (95% CI) of −2.27 (−4.36, −0.18) and P<0.05, however, no association was observed in premenopausal endometrial cancer cases with an SMD (95% CI) of −1.52 (−3.49, 0.45) and P>0.05. The low circulating APN level increases the risk of endometrial cancer, whereas the high APN level decreases this risk in postmenopausal women. Circulating APN as simple biomarkers may be a promising tool for the prevention, early diagnosis and disease monitoring of endometrial cancer. PMID:27284314

  3. Project for the National Program of Early Diagnosis of Endometrial Cancer Part II

    PubMed Central

    Bohîlțea, RE; Ancăr, V; Rădoi, V; Furtunescu, F; Bohîlțea, LC

    2015-01-01

    Rationale: Endometrial cancer recorded a peak incidence in ages 60-64 years in Romania. Since 2013, an increased trend of endometrial cancer occurrence has been registered in urban areas as compared with rural ones. Unfortunately, most of the cancer cases are diagnosed too late, in an advanced stage of the disease, resulting into diminished lifetime expectancy. The first part of the article concentrated on issues such as: the description of the study, results, and discussions regarding the study, definitions and terms, risk factors specific for endometrial carcinomas, presentation of the activities of the Program, etc. Objective: Drafting a national program that will serve as an early diagnosis method of endometrial cancer. This second part of the study continues with the presentation of the activities of the Program, analyzes the human resources and materials needed to implement the Program, presents the strategies and the indicators specific for the implementation of the project. Methods and Results: A standardization of the diagnostic steps was proposed and the focus was on 4 key elements for the early diagnosis of endometrial cancer: The first steps were approached in the first part of the study and the second part of the study investigated the proper monitoring of precursor endometrial lesions or cancer associated endometrial lesions and screening high risk populations (Lynch syndrome, Cowden syndrome). Discussion: Improving medical practice based on diagnostic algorithms and programs improves and increases the lifetime expectancy, due to the fact that endometrial cancer is early diagnosed and treated before it causes serious health problems or even death. Abbreviations: ASCCP = American Society for Colposcopy and Cervical Pathology, CT = Computerized Tomography, HNPCC = Hereditary Nonpolyposis Colorectal Cancer (Lynch syndrome), IHC = Immunohistochemistry, MSI = Microsatellites instability, MSI-H/ MSI-L = high (positive test)/ low (negative test

  4. Obesity, inflammatory markers, and endometrial cancer risk: a prospective case–control study

    PubMed Central

    Dossus, Laure; Rinaldi, Sabina; Becker, Susen; Lukanova, Annekatrin; Tjonneland, Anne; Olsen, Anja; Stegger, Jakob; Overvad, Kim; Chabbert-Buffet, Nathalie; Jimenez-Corona, Aida; Clavel-Chapelon, Francoise; Rohrmann, Sabine; Teucher, Birgit; Boeing, Heiner; Schütze, Madlen; Trichopoulou, Antonia; Benetou, Vassiliki; Lagiou, Pagona; Palli, Domenico; Berrino, Franco; Panico, Salvatore; Tumino, Rosario; Sacerdote, Carlotta; Redondo, Maria-Luisa; Travier, Noémie; Sanchez, Maria-Jose; Altzibar, Jone M; Chirlaque, Maria-Dolores; Ardanaz, Eva; Bueno-de-Mesquita, H Bas; van Duijnhoven, Fränzel J B; Onland-Moret, N Charlotte; Peeters, Petra H M; Hallmans, Goran; Lundin, Eva; Khaw, Kay-Tee; Wareham, Nicholas; Allen, Naomi; Key, Tim J; Slimani, Nadia; Hainaut, Pierre; Romaguera, Dora; Norat, Teresa; Riboli, Elio; Kaaks, Rudolf

    2010-01-01

    Obesity, a major risk factor for endometrial cancer, is a low-grade inflammatory state characterized by elevated concentrations of cytokines and acute phase reactants. The current study had two aims: first to investigate the associations of C-reactive protein (CRP), interleukin 6 (IL6), and IL1 receptor antagonist (IL1Ra) with endometrial cancer risk and second to examine to which extent these markers can influence the association between obesity and endometrial cancer. We conducted a case–control study, nested within the European Prospective Investigation into Cancer and Nutrition, which comprised 305 incident cases of endometrial cancer and 574 matched controls. CRP, IL6, and IL1Ra were measured in prospectively collected blood specimens by immunoassays. Data were analyzed using conditional logistic regression. All statistical tests were two-sided, and P values <0.05 were considered statistically significant. We observed a significant increase in risk of endometrial cancer with elevated levels of CRP (odds ratio (OR) for top versus bottom quartile: 1.58, 95% confidence interval (CI): 1.03–2.41, Ptrend=0.02), IL6 (OR for top versus bottom quartile: 1.66, 95% CI: 1.08–2.54, Ptrend=0.008), and IL1Ra (OR for top versus bottom quartile: 1.82, 95% CI: 1.22–2.73, Ptrend=0.004). After adjustment for body mass index (BMI), the estimates were strongly reduced and became non-significant. The association between BMI and endometrial cancer was also substantially attenuated (∼10–20%) after adjustment for inflammatory markers, even when the effects of C-peptide or estrone had already been taken into account. We provided epidemiological evidence that chronic inflammation might mediate the association between obesity and endometrial cancer and that endometrial carcinogenesis could be promoted by an inflammatory milieu. PMID:20843938

  5. Female Hormonal Factors and the Risk of Endometrial Cancer in Lynch Syndrome

    PubMed Central

    Dashti, Seyedeh Ghazaleh; Chau, Rowena; Ouakrim, Driss Ait; Buchanan, Daniel D.; Clendenning, Mark; Young, Joanne P.; Winship, Ingrid M.; Arnold, Julie; Ahnen, Dennis J.; Haile, Robert W.; Casey, Graham; Gallinger, Steven; Thibodeau, Stephen N.; Lindor, Noralane M.; Le Marchand, Loïc; Newcomb, Polly A.; Potter, John D.; Baron, John A.; Hopper, John L.; Jenkins, Mark A.; Win, Aung Ko

    2015-01-01

    Importance Apart from hysterectomy, there is no consensus recommendation for reducing endometrial cancer risk for women with a mismatch repair (MMR) gene mutation (Lynch syndrome). Objective To investigate the association between hormonal factors and endometrial cancer risk in Lynch syndrome. Design, Setting, and Participants A retrospective cohort study including 1,128 women with a MMR gene mutation identified from the Colon Cancer Family Registry was conducted. Data were analyzed using a weighted cohort approach. Participants were recruited between 1997 and 2012, from centers across the United States, Australia, Canada, and New Zealand. Exposures Age at menarche, first and last live birth, and menopause, number of live births, hormonal contraceptive use, and postmenopausal hormone use. Main Outcome and Measures Self-reported diagnosis of endometrial cancer. Results Endometrial cancer was diagnosed in 133 women (incidence per 100 person-years, 0.29; 95% confidence interval [CI], 0.24 to 0.34). A lower risk of endometrial cancer was associated with later age at menarche (hazard ratio [HR] per year, 0.85 [95%CI, 0.73 to 0.99]; P=.04), parity (parous vs nulliparous: HR, 0.21 [95%CI, 0.10 to 0.42]; P<.001), and hormonal contraceptive use (≥1 year vs <1 year: HR, 0.39 [95%CI, 0.23 to 0.64]; P<.001). There was no statistically significant association between endometrial cancer and age at first and last live birth, age at menopause, and postmenopausal hormone use. Conclusions and Relevance For women with a MMR gene mutation, some endogenous and exogenous hormonal factors were associated with a lower risk of endometrial cancer. These directions and strengths of associations were similar to those for the general population. If replicated, these findings suggest that women with a MMR gene mutation may be counseled like the general population in regard to hormonal influences on endometrial cancer risk. PMID:26151267

  6. The soluble EP2 receptor FuEP2/Ex2 suppresses endometrial cancer cell growth in an orthotopic xenograft model in nude mice.

    PubMed

    Takahashi, Tetsuyuki; Ogawa, Hirohisa; Izumi, Keisuke; Uehara, Hisanori

    2011-07-01

    Endometrial cancer is one of the most common gynecologic malignancies and many factors influence in its growth and development. As in many other types of cancer, prostaglandin E(2) (PGE(2)) is thought to be an accelerator of cell proliferation and endometrial cancer progression. In this study, we examined the effect of FuEP2/Ex2, a soluble decoy receptor for PGE(2) on growth of endometrial cancer cells. A stable transfectant expressing FuEP2/Ex2 was established from human endometrial cancer Ishikawa cells (Ish-FuEP2/Ex2). Ish-FuEP2/Ex2 cells expressed FuEP2/Ex2 mRNA and protein. Expression levels of E-prostanoid receptor 1 (EP1), EP2, EP3, EP4, and F-prostanoid receptor (FP) were almost the same in Ish-FuEP2/Ex2 and vector control cells. Growth rates of Ish-FuEP2/Ex2 under normal culture conditions were also similar to vector control cells, although PGE(2)-induced growth stimulation was completely inhibited in Ish-FuEP2/Ex2 or by Ish-FuEP2/Ex2 culture medium. Moreover, phosphorylation of extracellular signal-regulated kinase (ERK) and induction of cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF), cyclin D1, and c-fos mRNA by PGE(2) were not observed in Ish-FuEP2/Ex2 and Ish-FuEP2/Ex2 culture medium-treated vector control cells, although they were found when treated with prostaglandin F(2α). An orthotopic xenograft model in athymic nude mice revealed that Ish-FuEP2/Ex2-injected mice had significantly decreased mean tumor area. The proportion of Ki-67-positive cells in the tumor lesion was also significantly lower in Ish-FuEP2/Ex2-injected mice. These findings suggest that an EP-targeting strategy using FuEP2/Ex2 may be of use in the treatment of endometrial cancer.

  7. Modeling All Dialogue System Participants to Generate Empathetic Responses

    PubMed Central

    Haimowitz, Ira J.

    1990-01-01

    We describe a dialogue system between an expert system and its users which combines two recent hypotheses. First, that the dialogue system should explicitly model both the person directly interacting with the dialogue system (the agent) and the person reasoned about by the expert system (the patient) in order to communicate meaningfully with both people. Second, that a dialogue system can model the domain-related beliefs, preferences and concerns of both its users and generate responses empathetic to both. This dialogue system is called SERUM, standing for “System for Empathetic Responses with User Models.” Serum generates natural language responses about attribute values of domain objects, via three transformations. First the system converts properties of the agent and patient, and domain knowledge, into a pragmatic objective like empathy. Second SERUM converts the pragmatic objectives into surface structure cues like object emphasis and level of technicality. Finally SERUM converts the surface structure cues to realize text that is natural, appropriately technical, and downplaying or off-setting information that is unpleasant or undesirable to the agent or patient. Serum is demonstrated in the sensitive medical domain of lung disease for AIDS patients, where empathetic responses may be needed.

  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. Expression of placental protein 14 by the new endometrial cancer cell line MFE-280 in vitro and by endometrial carcinomas in vivo.

    PubMed

    Hackenberg, R; Loos, S; Nia, A H; Kunzmann, R; Schulz, K D

    1998-01-01

    MFE-280 endometrial cancer cells express PP14 (placental protein 14) in vitro. PP14 is normally found in the secretory endometrium and in placental tissue. MFE-280 cells, which are tumorigenic in nude mice, were derived from a recurrent, poorly differentiated endometrial carcinoma. The cells were initially grown in suspension culture and later transferred to monolayer cultures. Karyotyping revealed near-diploidy with a complex heterogeneous aberration pattern. MFE-280 cells were positive for the cytokeratins 7, 8, 18 and 19 as well as for vimentin. The expression of PP14 in MFE-280 cells was demonstrated by immunochemistry and reverse transcriptase--polymerase chain reaction. PP14-mRNA was also detected in one out of five endometrial cancer specimen. In tumor tissue the expression of PP14 was not dependent on progestins.

  10. Cytokines and the hypothalamic-pituitary-ovarian-endometrial axis.

    PubMed

    Tabibzadeh, S

    1994-05-01

    Recently, the demarcating boundaries that allowed separation of the fields of reproductive biology, endocrinology, immunology and neurobiology have faded. The missing link that now ties these disciplines together is the understanding that the language by which cells communicate within these diverse systems is unanimous. This language is the network of products collectively called cytokines. The effect of these factors spans from the hypothalamus to the endometrium and is undoubtedly involved in the maintenance of the delicate balance within the hypothalamic-pituitary-gonadal-endometrial axis. Orchestrated networks of these cytokines also seem to be linked to the steroid hormone signals, an essential feature for maintenance of normal menstrual cycles. Evidence in favour of these emerging concepts is discussed. Major emphasis is placed on interferons, interleukins, tumour necrosis factor, transforming growth factors and colony-stimulating factors.

  11. Endometrial adenocarcinoma, adjuvant radiotherapy tailored to prognostic factors.

    PubMed

    Meerwaldt, J H; Hoekstra, C J; van Putten, W L; Tjokrowardojo, A J; Koper, P C

    1990-02-01

    The optimal adjuvant radiotherapy for surgically treated endometrial cancer has not yet been defined. We report on 389 patients treated between 1970 and 1985 with adjuvant radiotherapy. The treatment was tailored to the known prognostic factors: myometrial invasion and grade of differentiation of the tumor. Ten-year overall survival was 67%, 10-year relapse-free survival 77%; 23% relapse, of which 21% distant and 6% locoregional relapse. In a multivariate analysis, stage (pT), grade, and myometrial invasion were prognostic factors. The number of locoregional failures was very small (n = 23). This small number, the fact that radiation treatment was tailored to prognostic factors, and the absence of a nontreated control group precluded an analysis of the effect of the adjuvant irradiation. Large randomized studies with a control (no treatment) arm should be performed to determine the value of adjuvant radiotherapy. PMID:2303362

  12. [Chemotherapy of metastatic endometrial carcinoma. Review of the literature].

    PubMed

    Pierga, J Y; Dieras, V; Paraiso, D; Pouillart, P

    1995-12-01

    Endometrial carcinoma is one of the most common gynaecological cancers in Western countries. About 75% of the patients present limited disease, confined to the uterus that can be cured by surgery. However, one third of the patients will need systemic treatment because of metastatic or relapsing disease. Hormonotherapy response rates are less than 20%. In monochemotherapy, the higher response rates are constantly observed with doxorubicin or cisplatinum (25-35%). Most commonly used combination are CAP (cyclophosphamide, doxorubicin, cisplatinum) or AP (doxorubicin, cisplatinum), giving 35 to 60% of objective responses. Recent results of large randomized trials have demonstrated marginal, if any, effect of cyclophosphamide and superiority of doxorubicin-cisplatinum combination compared to doxorubicin alone for response and survival. Chemotherapy as hormonotherapy remains palliative. Median response duration is 4 to 6 months and median overall survival duration is 7 to 10 months. Currently, hormonotherapy-chemotherapy combination have not been proved to be more effective than chemotherapy alone.

  13. [Myxoid mesenchymal tumors of uterus: endometrial stromal and smooth muscle tumors, myxoid variant].

    PubMed

    Chesnais, Anne-Laure; Watkin, Emmanuel; Beurton, Daniel; Devouassoux-Shisheboran, Mojgan

    2011-06-01

    Four myxoid variant of uterine mesenchymal tumors are reported. One was a low grade stromal sarcoma with infiltrative margins and the others were well circumscribed tumors corresponding to an endometrial stromal nodule and two leiomyomas. They were hypocellular neoplasms composed of stellated cells with an abundant Alcian Blue positive myxoid matrix. The myxoid nature of the neoplasms obscured their cellular nature and made the distinction between smooth muscle and endometrial stromal tumors difficult. Endometrial stromal tumors, showed very focal areas of small basophilic cells, characteristic of endometrial stroma. The diagnosis was based on the presence of a spiral arteriolar network, a CD10 positivity as well as the absence of h-caldesmon and desmin expression. The two myxoid leiomyomas showed more spindle cells and a desmin expression while h-caldesmon was negative and CD10 focally positive in both cases. Myxoid variant of endometrial stromal tumors does not necessarily exhibit the typical morphology of endometrial stroma. They may demonstrate morphological features of smooth muscle tumors in the uterus. Also, myxoid changes in uterin smooth muscle tumors may modify the classical immunoreactivity of smooth muscle markers in these tumors and make it difficult to distinguish between benign and malignant neoplasms. An immunohistochemical panel of antibodies including CD10, h-caldesmon and desmin may help in establishing the correct diagnosis.

  14. Surgical Management of Early Endometrial Cancer: An Update and Proposal of a Therapeutic Algorithm

    PubMed Central

    Falcone, Francesca; Balbi, Giancarlo; Di Martino, Luca; Grauso, Flavio; Salzillo, Maria Elena; Messalli, Enrico Michelino

    2014-01-01

    In the last few years technical improvements have produced a dramatic shift from traditional open surgery towards a minimally invasive approach for the management of early endometrial cancer. Advancement in minimally invasive surgical approaches has allowed extensive staging procedures to be performed with significantly reduced patient morbidity. Debate is ongoing regarding the choice of a minimally invasive approach that has the most effective benefit for the patients, the surgeon, and the healthcare system as a whole. Surgical treatment of women with presumed early endometrial cancer should take into account the features of endometrial disease and the general surgical risk of the patient. Women with endometrial cancer are often aged, obese, and with cardiovascular and metabolic comorbidities that increase the risk of peri-operative complications, so it is important to tailor the extent and the radicalness of surgery in order to decrease morbidity and mortality potentially derivable from unnecessary procedures. In this regard women with negative nodes derive no benefit from unnecessary lymphadenectomy, but may develop short- and long-term morbidity related to this procedure. Preoperative and intraoperative techniques could be critical tools for tailoring the extent and the radicalness of surgery in the management of women with presumed early endometrial cancer. In this review we will discuss updates in surgical management of early endometrial cancer and also the role of preoperative and intraoperative evaluation of lymph node status in influencing surgical options, with the aim of proposing a management algorithm based on the literature and our experience. PMID:25063051

  15. Diagnosis of Endometrial-Factor Infertility: Current Approaches and New Avenues for Research

    PubMed Central

    Katzorke, N.; Vilella, F.; Ruiz, M.; Krüssel, J.-S.; Simón, C.

    2016-01-01

    Over the last decade, research to improve success rates in reproductive medicine has focused predominantly on the understanding and optimization of embryo quality. However, the emergence of personalized medicine in ovulation induction and embryology has shifted the focus to assessing the individual status of the endometrium. The endometrium is considered receptive during an individually defined period, the window of implantation (WOI), when the mother permits a blastocyst to attach and implant. This individual receptivity status can now be objectively diagnosed using the endometrial receptivity array (ERA) developed in 2011. The ERA, together with a computational algorithm, detects the unique transcriptomic signature of endometrial receptivity by analyzing 238 differentially expressed genes and reliably predicting the WOI. We and others have illustrated the utility of this personalized diagnostic approach to discriminate between individual physiological variation in endometrial receptivity and unknown endometrial pathology, deemed as causal in recurrent implantation failure (RIF). An international randomized controlled trial (“The ERA as a diagnostic guide for personalized embryo transfer.” ClinicalTrials.gov Identifier: NCT01954758) is underway to determine the clinical value of this endometrial diagnostic intervention in the work-up for reproductive care. In this review, we analyse the current clinical practice in the diagnosis of the endometrial factor together with new avenues of research. PMID:27365540

  16. Genetic alterations in endometrial cancer by targeted next-generation sequencing.

    PubMed

    Chang, Ya-Sian; Huang, Hsien-Da; Yeh, Kun-Tu; Chang, Jan-Gowth

    2016-02-01

    Many genetic factors play important roles in the development of endometrial cancer. The aim of this study was to investigate genetic alterations in the Taiwanese population with endometrial cancer. DNA was extracted from 10 cases of fresh-frozen endometrial cancer tissue. The exomes of cancer-related genes were captured using the NimbleGen Comprehensive Cancer Panel (578 cancer-related genes) and sequenced using the Illumina Genomic Sequencing Platform. Our results revealed 120 variants in 99 genes, 21 of which were included in the Oncomine Cancer Research Panel used in the National Cancer Institute Match Trial. The 21 genes comprised 8 tumor suppressor candidates (ATM, MSH2, PIK3R1, PTCH1, PTEN, TET2, TP53, and TSC1) and 13 oncogene candidates (ALK, BCL9, CTNNB1, ERBB2, FGFR2, FLT3, HNF1A, KIT, MTOR, PDGFRA, PPP2R1A, PTPN11, and SF3B1). We identified a high frequency of mutations in PTEN (50%) and genes involved in the endometrial cancer-related molecular pathway, which involves the IL-7 signaling pathway (PIK3R1, n=1; AKT2, n=1; FOXO1, n=1). We report the mutational landscape of endometrial cancer in the Taiwanese population. We believe that this study will shed new light on fundamental aspects for understanding the molecular pathogenesis of endometrial cancer and may aid in the development of new targeted therapies. PMID:26626801

  17. Subsequent endometrial carcinoma with adjuvant tamoxifen treatment in Japanese breast cancer patients.

    PubMed

    Nishimura, N; Hachisuga, T; Saito, T; Kawarabayashi, T

    2001-01-01

    This study aimed to detail the clinicopathologic features of endometrial carcinomas that developed in Japanese patients receiving adjuvant tamoxifen treatment for breast cancer patients. Ten endometrial carcinomas in tamoxifen-treated breast cancer patients were collected from two medical centers. The endometrial carcinomas included two stage Ia, four stage Ib, two stage Ic and two stage IIIc. Three tumors were Grade 1, six were Grade 2, and one was Grade 3. The tumor was limited to the endometrium in two cases. Myometrial invasion was limited to the inner half of the myometrium in five cases and involved the outer half in three. A mild degree of lymphovascular space invasion was identified in five cases. Deep cervical invasion was recognized in one case. The cell types comprised nine endometrioid adenocarcinomas and one serous carcinoma. Five of eight postmenopausal endometrial carcinomas were associated with polypoid endometrial lesions composed of cystically dilated atrophic and proliferative glands widely separated by fibrotic stroma. Two patients with retroperitoneal lymph node metastases died of endometrial cancer. One patient developed a contralateral breast cancer during tamoxifen treatment. No patient died of breast cancer. We did not demonstrate a higher frequency of either high-grade tumors or unfavorable histologic subtypes in tamoxifen-treated Japanese breast cancer patients.

  18. Ovarian and endometrial endometrioid carcinomas have distinct CTNNB1 and PTEN mutation profiles.

    PubMed

    McConechy, Melissa K; Ding, Jiarui; Senz, Janine; Yang, Winnie; Melnyk, Nataliya; Tone, Alicia A; Prentice, Leah M; Wiegand, Kimberly C; McAlpine, Jessica N; Shah, Sohrab P; Lee, Cheng-Han; Goodfellow, Paul J; Gilks, C Blake; Huntsman, David G

    2014-01-01

    Ovarian endometrioid carcinomas and endometrial endometrioid carcinomas share many histological and molecular alterations. These similarities are likely due to a common endometrial epithelial precursor cell of origin, with most ovarian endometrioid carcinomas arising from endometriosis. To directly compare the mutation profiles of two morphologically similar tumor types, endometrial endometrioid carcinomas (n=307) and ovarian endometrioid carcinomas (n=33), we performed select exon capture sequencing on a panel of genes: ARID1A, PTEN, PIK3CA, KRAS, CTNNB1, PPP2R1A, TP53. We found that PTEN mutations are more frequent in low-grade endometrial endometrioid carcinomas (67%) compared with low-grade ovarian endometrioid carcinomas (17%) (P<0.0001). By contrast, CTNNB1 mutations are significantly different in low-grade ovarian endometrioid carcinomas (53%) compared with low-grade endometrial endometrioid carcinomas (28%) (P<0.0057). This difference in CTNNB1 mutation frequency may be reflective of the distinct microenvironments; the epithelial cells lining an endometriotic cyst within the ovary are exposed to a highly oxidative environment that promotes tumorigenesis. Understanding the distinct mutation patterns found in the PI3K and Wnt pathways of ovarian and endometrial endometrioid carcinomas may provide future opportunities for stratifying patients for targeted therapeutics.

  19. The potential role of elastography in differentiating between endometrial polyps and submucosal fibroids: a preliminary study

    PubMed Central

    2015-01-01

    Endometrial polyps and submucosal fibroids are common causes of abnormal uterine bleeding (AUB) and less commonly infertility. The prevalence of such intrauterine lesions increases with age during the reproductive years, and usually decreases after menopause. The first-line imaging examination in the diagnosis of endometrial polyps as well as submucosal fibroidsis ultrasound, but its accuracy is not obvious. Elastography is an ultrasound-based imaging modality that is used to assess the stiffness of examined tissues. Considering the fact that endometrial polyps derive from soft endometrial tissue and submucosal fibroids are made of hard muscle tissue, elastography seems a perfect tool to differentiate between such lesions. I present two groups of patients with AUB and intrauterine lesions suspected on ultrasound. In the first group of patients, elastography showed that the stiffness of the lesion was similar to the endometrium and softer than the myometrium. During hysteroscopies endometrial polyps were removed. In the second group of patients, elastography showed that the stiffness of the lesion was similar to the myometrium and harder than the endometrium. During hysteroscopies submucosal fibroids were removed. In both groups, the diagnosis was confirmed by the pathological examination in all cases. It was demonstrated that with the use of elastography it is possible to assess the stiffness of intrauterine lesions, which may be useful in differentiating between endometrial polyps and submucosal fibroids. PMID:26327901

  20. The potential role of elastography in differentiating between endometrial polyps and submucosal fibroids: a preliminary study.

    PubMed

    Woźniak, Sławomir

    2015-06-01

    Endometrial polyps and submucosal fibroids are common causes of abnormal uterine bleeding (AUB) and less commonly infertility. The prevalence of such intrauterine lesions increases with age during the reproductive years, and usually decreases after menopause. The first-line imaging examination in the diagnosis of endometrial polyps as well as submucosal fibroidsis ultrasound, but its accuracy is not obvious. Elastography is an ultrasound-based imaging modality that is used to assess the stiffness of examined tissues. Considering the fact that endometrial polyps derive from soft endometrial tissue and submucosal fibroids are made of hard muscle tissue, elastography seems a perfect tool to differentiate between such lesions. I present two groups of patients with AUB and intrauterine lesions suspected on ultrasound. In the first group of patients, elastography showed that the stiffness of the lesion was similar to the endometrium and softer than the myometrium. During hysteroscopies endometrial polyps were removed. In the second group of patients, elastography showed that the stiffness of the lesion was similar to the myometrium and harder than the endometrium. During hysteroscopies submucosal fibroids were removed. In both groups, the diagnosis was confirmed by the pathological examination in all cases. It was demonstrated that with the use of elastography it is possible to assess the stiffness of intrauterine lesions, which may be useful in differentiating between endometrial polyps and submucosal fibroids. PMID:26327901