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Sample records for ishikawa human endometrial

  1. Changes in the transcriptome of the human endometrial Ishikawa cancer cell line induced by estrogen, progesterone, tamoxifen, and mifepristone (RU486 as detected by RNA-sequencing.

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    Karin Tamm-Rosenstein

    Full Text Available BACKGROUND: Estrogen (E2 and progesterone (P4 are key players in the maturation of the human endometrium. The corresponding steroid hormone modulators, tamoxifen (TAM and mifepristone (RU486 are widely used in breast cancer therapy and for contraception purposes, respectively. METHODOLOGY/PRINCIPAL FINDINGS: Gene expression profiling of the human endometrial Ishikawa cancer cell line treated with E2 and P4 for 3 h and 12 h, and TAM and RU486 for 12 h, was performed using RNA-sequencing. High levels of mRNA were detected for genes, including PSAP, ATP5G2, ATP5H, and GNB2L1 following E2 or P4 treatment. A total of 82 biomarkers for endometrial biology were identified among E2 induced genes, and 93 among P4 responsive genes. Identified biomarkers included: EZH2, MDK, MUC1, SLIT2, and IL6ST, which are genes previously associated with endometrial receptivity. Moreover, 98.8% and 98.6% of E2 and P4 responsive genes in Ishikawa cells, respectively, were also detected in two human mid-secretory endometrial biopsy samples. TAM treatment exhibited both antagonistic and agonistic effects of E2, and also regulated a subset of genes independently. The cell cycle regulator cyclin D1 (CCND1 showed significant up-regulation following treatment with TAM. RU486 did not appear to act as a pure antagonist of P4 and a functional analysis of RU486 response identified genes related to adhesion and apoptosis, including down-regulated genes associated with cell-cell contacts and adhesion as CTNND1, JUP, CDH2, IQGAP1, and COL2A1. CONCLUSIONS: Significant changes in gene expression by the Ishikawa cell line were detected after treatments with E2, P4, TAM, and RU486. These transcriptome data provide valuable insight into potential biomarkers related to endometrial receptivity, and also facilitate an understanding of the molecular changes that take place in the endometrium in the early stages of breast cancer treatment and contraception usage.

  2. 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.

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    Erwan Guyot

    Full Text Available 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.

  3. 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

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    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

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

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    Salker, Madhuri S.; Zhou, Yuetao; Singh, Yogesh [Department of Physiology, University of Tuebingen, 72076 Tuebingen (Germany); Brosens, Jan [Division of Reproductive Health, Warwick Medical School, Clinical Sciences Research Laboratories, University Hospital, Coventry CV2 2DX (United Kingdom); Lang, Florian, E-mail: florian.lang@uni-tuebingen.de [Department of Physiology, University of Tuebingen, 72076 Tuebingen (Germany)

    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.

  5. [AntiEGFRnano inhibites proliferation and migration of estrogen-dependent Ishikawa cells of human endometrial cancer cell line].

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    Diao, Zhen-yu; Lu, Wu-guang; Cao, Peng; Hu, Yun-long; Zhou, Xing; Xue, Ping-ping; Shen, Li; Sun, Hai-xiang

    2012-10-01

    Nanobody is a kind of antibody from camel, which misses light chain. Nanobody has the same antigen binding specificity and affinity as mAb. Moreover, because of its small molecular weight, high stability and easy preparation, nanobody has great value of biomedical applications. In this study, we successfully prepared highly pure antiEGFR nanobody in E.coli using genetic engineering techniques. Cell proliferation assay (CCK-8 assay) and migration experiments (cell scratch test and Transwell assay) indicated that the recombinant antiEGFRnano can significantly inhibit the proliferation and migration of endometrial cancer cells. These results provide a new way of thinking and methods for EGFR-targeted therapy of endometrial cancer.

  6. T Ishikawa

    Indian Academy of Sciences (India)

    Home; Journals; Pramana – Journal of Physics. T Ishikawa. Articles written in Pramana – Journal of Physics. Volume 58 Issue 5-6 May-June 2002 pp 761-767 Strongly Correlated Electron Systems. X-ray magnetic circular dichroism at IrL2,3 edges in Fe100-Ir and Co100-Ir alloys: Magnetism of 5d electronic states.

  7. Studies Using an in Vitro Model Show Evidence of Involvement of Epithelial-Mesenchymal Transition of Human Endometrial Epithelial Cells in Human Embryo Implantation*

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    Uchida, Hiroshi; Maruyama, Tetsuo; Nishikawa-Uchida, Sayaka; Oda, Hideyuki; Miyazaki, Kaoru; Yamasaki, Akiko; Yoshimura, Yasunori

    2012-01-01

    Human embryo implantation is a critical multistep process consisting of embryo apposition/adhesion, followed by penetration and invasion. Through embryo penetration, the endometrial epithelial cell barrier is disrupted and remodeled by an unknown mechanism. We have previously developed an in vitro model for human embryo implantation employing the human choriocarcinoma cell line JAR and the human endometrial adenocarcinoma cell line Ishikawa. Using this model we have shown that stimulation with ovarian steroid hormones (17β-estradiol and progesterone, E2P4) and suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, enhances the attachment and adhesion of JAR spheroids to Ishikawa. In the present study we showed that the attachment and adhesion of JAR spheroids and treatment with E2P4 or SAHA individually induce the epithelial-mesenchymal transition (EMT) in Ishikawa cells. This was evident by up-regulation of N-cadherin and vimentin, a mesenchymal cell marker, and concomitant down-regulation of E-cadherin in Ishikawa cells. Stimulation with E2P4 or SAHA accelerated Ishikawa cell motility, increased JAR spheroid outgrowth, and enhanced the unique redistribution of N-cadherin, which was most prominent in proximity to the adhered spheroids. Moreover, an N-cadherin functional blocking antibody attenuated all events but not JAR spheroid adhesion. These results collectively provide evidence suggesting that E2P4- and implanting embryo-induced EMT of endometrial epithelial cells may play a pivotal role in the subsequent processes of human embryo implantation with functional control of N-cadherin. PMID:22174415

  8. Prevalence of Human Papillomavirus in endometrial cancer

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    Olesen, Tina Bech; Svahn, Malene Frøsig; Faber, Mette Tuxen

    2014-01-01

    HPV is a common sexually transmitted infection and is considered to be a necessary cause of cervical cancer. The anatomical proximity to the cervix has led researchers to investigate whether Human Papillomavirus (HPV) has a role in the etiology of endometrial cancer.......HPV is a common sexually transmitted infection and is considered to be a necessary cause of cervical cancer. The anatomical proximity to the cervix has led researchers to investigate whether Human Papillomavirus (HPV) has a role in the etiology of endometrial cancer....

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

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

    2012-01-01

    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

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

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    Fischer, L.; Deppert, W.R. [Department of Obstetrics and Gynecology, University Hospital Freiburg (Germany); Pfeifer, D. [Department of Hematology and Oncology, University Hospital Freiburg (Germany); Stanzel, S.; Weimer, M. [Department of Biostatistics, German Cancer Research Center, Heidelberg (Germany); Hanjalic-Beck, A.; Stein, A.; Straßer, M.; Zahradnik, H.P. [Department of Obstetrics and Gynecology, University Hospital Freiburg (Germany); Schaefer, W.R., E-mail: wolfgang.schaefer@uniklinik-freiburg.de [Department of Obstetrics and Gynecology, University Hospital Freiburg (Germany)

    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

  11. Human Endometrial CD98 Is Essential for Blastocyst Adhesion

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

    2010-01-01

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

  12. Black cohosh inhibits 17β-estradiol-induced cell proliferation of endometrial adenocarcinoma cells.

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    Park, So Yun; Kim, Hee Ja; Lee, Sa Ra; Choi, Youn-Hee; Jeong, Kyungah; Chung, Hyewon

    2016-10-01

    This study was conducted to investigate the effect of black cohosh (BC) extract on the proliferation and apoptosis of Ishikawa cells. Ishikawa human endometrial adenocarcinoma cells were treated with or without BC (1, 5, 10 and 25 μM) and cell proliferation and cytotoxicity were measured by CCK-8 assays and flow cytometry analysis. Additionally, Ishikawa cells were treated with 17β-estradiol (E2), E2 + progesterone and E2 + BC (5 and 10 μM) and the effect of BC and progesterone on E2-induced cell proliferation was analyzed. BC decreased the proliferation of Ishikawa cells at a dose-dependent rate compared with the control group (p < 0.05). The proliferation of Ishikawa cells increased in the presence of E2, whereas the subsequent addition of progesterone or BC decreased proliferation to the level of the control group (p < 0.05). The inhibitory effect of BC on E2-induced cell proliferation was greater than the inhibitory effect of progesterone. In conclusion, BC induces apoptosis in Ishikawa cells and suppresses E2-induced cell proliferation in Ishikawa cells. BC could be considered a candidate co-treatment agent of estrogen-dependent tumors, especially those involving endometrial cells.

  13. Do GnRH analogues directly affect human endometrial epithelial cell gene expression?

    KAUST Repository

    Zhang, Xiaomei

    2010-03-04

    We examined whether Gonadotrophin-releasing hormone (GnRH) analogues [leuprolide acetate (LA) and ganirelix acetate (GA)] modulate gene expression in Ishikawa cells used as surrogate for human endometrial epithelial cells in vitro. The specific aims were: (i) to study the modulatory effect of GnRH analogues by RT-PCR [in the absence and presence of E2 and P4, and cyclic adenosine monophos-phate (cAMP)] on mRNA expression of genes modulated during the window of implantation in GnRH analogues/rFSH-treated assisted reproductive technology cycles including OPTINEURIN (OPTN), CHROMATIN MODIFYING PROTEIN (CHMP1A), PROSAPOSIN (PSAP), IGFBP-5 and SORTING NEXIN 7 (SNX7), and (ii) to analyze the 5\\'-flanking regions of such genes for the presence of putative steroid-response elements [estrogen-response elements (EREs) and P4-response element (PREs)]. Ishikawa cells were cytokeratin+/vimentin2 and expressed ERa,ERb, PR and GnRH-R proteins. At 6 and 24 h, neither LA nor GA alone had an effect on gene expression. GnRH analogues alone or following E2 and/or P4 co-incubation for 24 h also had no effect on gene expression, but P4 significantly increased expression of CHMP1A.E2 + P4 treatment for 4 days, alone or followed by GA, had no effect, but E2 + P4 treatment followed by LA significantly decreased IGFBP-5 expression. The addition of 8-Br cAMP did not modify gene expression, with the exception of IGFBP-5 that was significantly increased. The GnRH analogues did not modify intracellular cAMP levels. We identified conserved EREs for OPN, CHMP1A, SNX7 and PSAP and PREs for SNX7. We conclude that GnRH analogues appear not to have major direct effects on gene expression of human endo-metrial epithelial cells in vitro. © The Author 2010. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org.

  14. Metformin inhibits 17β-estradiol-induced epithelial-to-mesenchymal transition via βKlotho-related ERK1/2 signaling and AMPKα signaling in endometrial adenocarcinoma cells.

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    Liu, Zhao; Qi, Shasha; Zhao, Xingbo; Li, Mingjiang; Ding, Sentai; Lu, Jiaju; Zhang, Hui

    2016-04-19

    The potential role of metformin in treating endometrial cancer remains to be explored. The current study investigated the role of metformin in 17β-estradiol-induced epithelial-mesenchymal transition (EMT) in endometrial adenocarcinoma cells. We found that 17β-estradiol promoted proliferation and migration, attenuated apoptosis in both estrogen receptor (ER) positive and ER negative endometrial adenocarcinoma cells (Ishikawa and KLE cells, respectively). Metformin abolished 17β-estradiol-induced cell proliferation and reversed 17β-estradiol-induced EMT in Ishikawa cells. In addition, metformin increased the expression of βKlotho, a fibroblast growth factors (FGFs) coreceptor, and decreased ERK1/2 phosphorylation in both Ishikawa and KLE cells. Decreased expression of βKlotho was noted in human endometrial adenocarcinomas, and plasmid-driven expression of βKlotho in Ishikawa cells abolished 17β-estradiol-induced EMT via inhibiting ERK1/2 signaling. βKlotho expression and metformin show synergetic effects on the proliferation and the EMT in Ishikawa cells. Furthermore, we demonstrated that the anti-EMT effects of metformin could be partly abolished by introducing Compound C, a specific AMPKα signaling inhibitor. In conclusion, metformin abolishes 17β-estradiol-induced cell proliferation and EMT in endometrial adenocarcinoma cells by upregulating βKlotho expression, inhibiting ERK1/2 signaling, and activating AMPKα signaling. Our study provides novel mechanistic insight into the anti-tumor effects of metformin.

  15. Estrogen induction of telomerase activity through regulation of the mitogen-activated protein kinase (MAPK dependent pathway in human endometrial cancer cells.

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    Chunxiao Zhou

    Full Text Available Given that prolonged exposure to estrogen and increased telomerase activity are associated with endometrial carcinogenesis, our objective was to evaluate the interaction between the MAPK pathway and estrogen induction of telomerase activity in endometrial cancer cells. Estradiol (E2 induced telomerase activity and hTERT mRNA expression in the estrogen receptor (ER-α positive, Ishikawa endometrial cancer cell line. UO126, a highly selective inhibitor of MEK1/MEK2, inhibited telomerase activity and hTERT mRNA expression induced by E2. Similar results were also found after transfection with ERK 1/2-specific siRNA. Treatment with E2 resulted in rapid phosphorylation of p44/42 MAPK and increased MAPK activity which was abolished by UO126. The hTERT promoter contains two estrogen response elements (EREs, and luciferase assays demonstrate that these EREs are activated by E2. Exposure to UO126 or ERK 1/2-specific siRNA in combination with E2 counteracted the stimulatory effect of E2 on luciferase activity from these EREs. These findings suggest that E2-induction of telomerase activity is mediated via the MAPK pathway in human endometrial cancer cells.

  16. Expression of epidermal growth factor receptors in human endometrial carcinoma

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    Nyholm, H C; Nielsen, Anette Lynge; Ottesen, B

    1993-01-01

    Little data exist on the expression of epidermal growth factor receptors (EGF-Rs) in human endometrial cancer. EGF-R status was studied in 65 patients with endometrial carcinomas and in 26 women with nonmalignant postmenopausal endometria, either inactive/atrophic endometrium or adenomatous...... hyperplasia. EGF-R was identified on frozen tissue sections by means of an indirect immunoperoxidase technique with a monoclonal antibody against the external domain of the EGF-R. Seventy-one percent of the carcinomas expressed positive EGF-R immunoreactivity. In general, staining was most prominent...

  17. Human embryo-conditioned medium stimulates in vitro endometrial angiogenesis

    NARCIS (Netherlands)

    Kapiteijn, K.; Koolwijk, P.; Weiden, R.M.F. van der; Nieuw Amerongen, G. van; Plaisier, M.; Hinsbergh, V.W.M. van; Helmerhorst, F.M.

    2006-01-01

    Objective: Successful implantation and placentation depend on the interaction between the endometrium and the embryo. Angiogenesis is crucial at this time. In this article we investigate the direct influence of the human embryo on in vitro endometrial angiogenesis. Design: In vitro study. Setting:

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

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    Qiansheng Huang

    2016-03-01

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

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

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    Mina Jafarabadi

    2017-08-01

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

  20. The antiprogesterone Org 31710 inhibits human blastocyst-endometrial interacttions in vitro

    DEFF Research Database (Denmark)

    Petersen, A; tin-Ley, U; Ravn, V

    2005-01-01

    OBJECTIVE: To investigate the effect of the anti-P Org 31710 on human blastocyst attachment to cultured endometrial epithelial cells. DESIGN: Experimental in vitro study. SETTING: University hospital. PATIENT(S): Eleven fertile endometrial donors. INTERVENTION(S): Timed endometrial biopsy for cell...... statistical significance. The presence of swollen microvilli, precursors of endometrial pinopodes, was significantly reduced on cultures with Org 31710 (P=.03). CONCLUSION(S): The study presents a model for human blastocyst-endometrial interactions responding to an anti-P drug. The exact mechanism...

  1. The antiprogesterone Org 31710 inhibits human blastocyst-endometrial interactions in vitro

    DEFF Research Database (Denmark)

    Petersen, Astrid; Bentin-Ley, Ursula; Ravn, Vibeke

    2005-01-01

    OBJECTIVE: To investigate the effect of the anti-P Org 31710 on human blastocyst attachment to cultured endometrial epithelial cells. DESIGN: Experimental in vitro study. SETTING: University hospital. PATIENT(S): Eleven fertile endometrial donors. INTERVENTION(S): Timed endometrial biopsy for cell...... statistical significance. The presence of swollen microvilli, precursors of endometrial pinopodes, was significantly reduced on cultures with Org 31710 (P=.03). CONCLUSION(S): The study presents a model for human blastocyst-endometrial interactions responding to an anti-P drug. The exact mechanism...

  2. Estrogenicity of glabridin in Ishikawa cells.

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    Melissa Su Wei Poh

    Full Text Available Glabridin is an isoflavan from licorice root, which is a common component of herbal remedies used for treatment of menopausal symptoms. Past studies have shown that glabridin resulted in favorable outcome similar to 17β-estradiol (17β-E2, suggesting a possible role as an estrogen replacement therapy (ERT. This study aims to evaluate the estrogenic effect of glabridin in an in-vitro endometrial cell line -Ishikawa cells via alkaline phosphatase (ALP assay and ER-α-SRC-1-co-activator assay. Its effect on cell proliferation was also evaluated using Thiazoyl blue tetrazolium bromide (MTT assay. The results showed that glabridin activated the ER-α-SRC-1-co-activator complex and displayed a dose-dependent increase in estrogenic activity supporting its use as an ERT. However, glabridin also induced an increase in cell proliferation. When glabridin was treated together with 17β-E2, synergistic estrogenic effect was observed with a slight decrease in cell proliferation as compared to treatment by 17β-E2 alone. This suggest that the combination might be better suited for providing high estrogenic effects with lower incidences of endometrial cancer that is associated with 17β-E2.

  3. Biological effects of plasma rich in growth factors (PRGF) on human endometrial fibroblasts.

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    Anitua, Eduardo; de la Fuente, María; Ferrando, Marcos; Quintana, Fernando; Larreategui, Zaloa; Matorras, Roberto; Orive, Gorka

    2016-11-01

    To evaluate the biological outcomes of plasma rich in growth factors (PRGF) on human endometrial fibroblasts in culture. PRGF was obtained from three healthy donors and human endometrial fibroblasts (HEF) were isolated from endometrial specimens from five healthy women. The effects of PRGF on cell proliferation and migration, secretion of vascular endothelial growth factor (VEGF), procollagen type I and hyaluronic acid (HA) and contractility of isolated and cultured human endometrial fibroblasts (HEF) were analyzed. Statistical analysis was performed in order to compare the effects of PRGF with respect to control situation (T-test or Mann-Whitney U-test). We report a significantly elevated human endometrial fibroblast proliferation and migration after treatment with PRGF. In addition, stimulation of HEF with PRGF induced an increased expression of the angiogenic factor VEGF and favored the endometrial matrix remodeling by the secretion of procollagen type I and HA and endometrial regeneration by elevating the contractility of HEF. These results were obtained for all PRGF donors and each endometrial cell line. The myriad of growth factors contained in PRGF promoted HEF proliferation, migration and synthesis of paracrine molecules apart from increasing their contractility potential. These preliminary results suggest that PRGF improves the biological activity of HEF in vitro, enhancing the regulation of several cellular processes implied in endometrial regeneration. This innovative treatment deserves further investigation for its potential in "in vivo" endometrial development and especially in human embryo implantation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. Gene expression profiling in Ishikawa cells: A fingerprint for estrogen active compounds

    International Nuclear Information System (INIS)

    Boehme, Kathleen; Simon, Stephanie; Mueller, Stefan O.

    2009-01-01

    Several anthropogenous and naturally occurring substances, referred to as estrogen active compounds (EACs), are able to interfere with hormone and in particular estrogen receptor signaling. EACs can either cause adverse health effects in humans and wildlife populations or have beneficial effects on estrogen-dependent diseases. The aim of this study was to examine global gene expression profiles in estrogen receptor (ER)-proficient Ishikawa plus and ER-deficient Ishikawa minus endometrial cancer cells treated with selected well-known EACs (Diethylstilbestrol, Genistein, Zearalenone, Resveratrol, Bisphenol A and o,p'-DDT). We also investigated the effect of the pure antiestrogen ICI 182,780 (ICI) on the expression patterns caused by these compounds. Transcript levels were quantified 24 h after compound treatment using Illumina BeadChip Arrays. We identified 87 genes with similar expression changes in response to all EAC treatments in Ishikawa plus. ICI lowered the magnitude or reversed the expression of these genes, indicating ER dependent regulation. Apart from estrogenic gene regulation, Bisphenol A, o,p'-DDT, Zearalenone, Genistein and Resveratrol displayed similarities to ICI in their expression patterns, suggesting mixed estrogenic/antiestrogenic properties. In particular, the predominant antiestrogenic expression response of Resveratrol could be clearly distinguished from the other test compounds, indicating a distinct mechanism of action. Divergent gene expression patterns of the phytoestrogens, as well as weaker estrogenic gene expression regulation determined for the anthropogenous chemicals Bisphenol A and o,p'-DDT, warrants a careful assessment of potential detrimental and/or beneficial effects of EACs. The characteristic expression fingerprints and the identified subset of putative marker genes can be used for screening chemicals with an unknown mode of action and for predicting their potential to exert endocrine disrupting effects

  5. LEFTY2 Controls Migration of Human Endometrial Cancer Cells via Focal Adhesion Kinase Activity (FAK) and miRNA-200a.

    Science.gov (United States)

    Alowayed, Nour; Salker, Madhuri S; Zeng, Ni; Singh, Yogesh; Lang, Florian

    2016-01-01

    LEFTY2, a suppressor of cell proliferation, tumor growth, regulator of stemness and embryonic differentiation, is a negative regulator of cancer cell reprogramming. Malignant transformation may lead to migration requiring loss of adhesion and gain of migratory activity. Signaling involved in the orchestration of migration, proliferation and spreading of cells include focal adhesion kinase (FAK) and adhesion molecule E-cadherin. The present study explored whether LEFTY2 influences the proliferation marker MKi67, FAK activity, E-cadherin abundance and migration of Ishikawa human endometrial carcinoma cells. Moreover, the study explored the involvement of microRNA-200a (miR-200a), which is known to regulate cellular adhesion by targeting E-Cadherin. FAK activity was estimated from FAK phosphorylation quantified by Western blotting, migration utilizing a wound healing assay, miR-200a and MKi67 expression levels utilizing qRT-PCR, cell proliferation and apoptosis using BrdU and Annexin V staining, respectively, and E-Cadherin (E-Cad) abundance, using confocal microscopy. LEFTY2 (25 ng/ml, 48 hours) treatment was followed by decrease of MKi67 expression, FAK activity and migration. LEFTY2 upregulated miRNA-200a and E-Cad protein level in Ishikawa cells. The effect of LEFTY2 on migration was mimicked by FAK inhibitor PF 573228 (50 µM). Addition of LEFTY2 in the presence of PF-573228 did not result in a further significant decline of migration. In conclusion, LEFTY2 down-regulates MKi67 expression and FAK activity, up-regulates miR-200a and E-cadherin, and is thus a powerful negative regulator of endometrial cell proliferation and migration. © 2016 The Author(s) Published by S. Karger AG, Basel.

  6. Photoaffinity labeling of the progesterone receptor from human endometrial carcinoma

    International Nuclear Information System (INIS)

    Clarke, C.L.; Satyaswaroop, P.G.

    1985-01-01

    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- 3 H]promegestone ([ 3 H]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 [ 3 H]R5020 was observed in EnCa 101 grown in the absence of estrogen, nor was any observed in EnCa K or EnCa V

  7. Enhanced caveolin-1 expression increases migration, anchorage-independent growth and invasion of endometrial adenocarcinoma cells

    International Nuclear Information System (INIS)

    Diaz-Valdivia, Natalia; Bravo, Denisse; Huerta, Hernán; Henriquez, Soledad; Gabler, Fernando; Vega, Margarita; Romero, Carmen; Calderon, Claudia; Owen, Gareth I.; Leyton, Lisette; Quest, Andrew F. G.

    2015-01-01

    Caveolin-1 (CAV1) has been implicated both in tumor suppression and progression, whereby the specific role appears to be context dependent. Endometrial cancer is one of the most common malignancies of the female genital tract; however, little is known about the role of CAV1 in this disease. Here, we first determined by immunohistochemistry CAV1 protein levels in normal proliferative human endometrium and endometrial tumor samples. Then using two endometrial cancer cell lines (ECC: Ishikawa and Hec-1A) we evaluated mRNA and protein levels of CAV1 by real time qPCR and Western blot analysis, respectively. The role of CAV1 expression in ECC malignancy was further studied by either inducing its expression in endometrial cancer cells with the tumor promotor 12-O-tetradecanoyl-phorbol-13-acetate (4β-TPA) or decreasing expression using short-hairpin RNA constructs, and then evaluating the effects of these changes on ECC proliferation, transmigration, matrigel invasion, and colony formation in soft agar. Immunohistochemical analysis of endometrial epithelia revealed that substantially higher levels of CAV1 were present in endometrial tumors than the normal proliferative epithelium. Also, in Ishikawa and Hec-1A endometrial cancer cells CAV1 expression was readily detectable. Upon treatment with 4β-TPA CAV1 levels increased and coincided with augmented cell transmigration, matrigel invasion, as well as colony formation in soft agar. Reduction of CAV1 expression using short-hairpin RNA constructs ablated these effects in both cell types whether treated or not with 4β-TPA. Alternatively, CAV1 expression appeared not to modulate significantly proliferation of these cells. Our study shows that elevated CAV1, observed in patients with endometrial cancer, is linked to enhanced malignancy of endometrial cancer cells, as evidenced by increased migration, invasion and anchorage-independent growth. The online version of this article (doi:10.1186/s12885-015-1477-5) contains

  8. Human endometrial milk fat globule-epidermal growth factor 8 (MFGE8) is up regulated by estradiol at the transcriptional level, and its secretion via microvesicles is stimulated by human chorionic gonadotropin (hCG)

    KAUST Repository

    Sarhan, Abbaa

    2013-10-17

    Objective: We have recently showed that MFGE8, a novel epithelial cell protein in the human endometrium, upregulated during the window of implantation. We hypothesized that MFGE8 may act as a key modulator of endometrial remodeling and trophoblast invasion. The aims of this study were (i) to investigate the in vitro regulation of human endometrial epithelial cells MFGE8 transcription, translation, and secretion by sex steroids and hCG; and (ii) to examine the possibility of MFGE8 secretion via microvesicles. Design: Experimental in vitro study using Ishikawa cells. Setting: University center. Interventions: Treatment with estradiol (E2), progesterone (P4), and human chorionic gonatropin (hCG). Main outcome measures: MFGE8 mRNA and protein expression, and identification of secreted microvesicles by mass spectrometry (MS) and immunoblotting. Results: E2, but not P4 or hCG, significantly upregulated MFGE8 mRNA expression. hCG significantly increased MFGE8 secretion. Microvesicels obtained after ultracentrifugation were visualized with atomic force microscopy ranging from ~100 to 200 nm. In addition to the expected 46 kD protein, the microvesicles contained a second form of secreted MFGE8 measuring ~30 kD which was confirmed by MS. Conclusions: We demonstrated (i) dual effects of E2 and hCG on the regulation of MFGE8, and (ii) MFGE8 protein secretion in association with microvesicles. MFGE8 has the potential to modulate endometrial function and implantation via exocrine and/ or paracrine-autocrine effects. To the best of our knowledge, this is the first demonstration of microvesicular secretion of any regulatory protein by endometrial epithelial cells, providing initial evidence suggestive of microvesicular participation in cellular trafficking information in the non-pregnant and pregnant endometrium.

  9. Dual-specificity phosphatase 6 (Dusp6), a negative regulator of FGF2/ERK1/2 signaling, enhances 17β-estradiol-induced cell growth in endometrial adenocarcinoma cell.

    Science.gov (United States)

    Zhang, Hui; Guo, Qiufen; Wang, Chong; Yan, Lei; Fu, Yibing; Fan, Mingjun; Zhao, Xingbo; Li, Mingjiang

    2013-08-25

    Dual-specificity phosphatase 6 (Dusp6) is a negative feedback mechanism of fibroblast growth factors (FGFs)/mitogen-activated protein kinase (MAPK)/ERK1/2 signaling. The aim of this study was to explore the expression of Dusp6 in human endometrial adenocarcinomas and the role of Dusp6 expression in the growth regulation of endometrial adenocarcinoma cell. We found that Dusp6 was over-expressed in human endometrial adenocarcinomas. In Ishikawa cells, plasmid-driven Dusp6 expression efficiently blocked the activity of FGF2-induced MAPK/ERK1/2 signaling. Unexpectedly, Dusp6 expression significantly enhanced the growth of Ishikawa cells. In Dusp6 forced-expression cells, 17β-estradiol stimulation increased the cell growth by all most threefolds. In addition, progesterone treatment reduced the cell growth to about half both in Ishikawa cells with and without forced-Dusp6-expression. Dusp6 over-expression is involved in the pathogenesis and development of human endometrial adenocarcinomas. Dusp6 functions as a negative regulator of FGF2/ERK1/2 signaling but enhances the growth and 17β-estradiol-induced cell growth in endometrial adenocarcinoma cell. Copyright © 2013. Published by Elsevier Ireland Ltd.

  10. Estradiol stimulation of inositolphospholipid metabolism in human endometrial fibroblasts

    International Nuclear Information System (INIS)

    Iida, K.; Imai, A.; Tamaya, T.

    1989-01-01

    Stimulated inositolphospholipid turnover has been proposed to constitute a signal-transducing mechanism in many cell types. To determine the inositolphospholipid turnover during stimulation by 17 beta-estradiol, the turnover kinetics of phospholipids was investigated in human endometrial fibroblasts. In cells incubated with [ 32 P] phosphate for 1 h, estradiol rapidly and persisitently (for at least 30 min) enhanced the rate of 32 P-labeling of phosphatidic acid (PA). On the other hand, after a lag time of 5 min, 32 P-labeling of phosphatidylinositol (PI) was also increased also. These sequential 32 P-labeling of PA and PI demonstrated that inositolphospholipid turnover was stimulated in fibroblasts exposed to estradiol. The rapid estrogen-stimulated inositolphospholipid turnover may not be through the mechanism associated with classical action of estrogen

  11. Steroids Regulate CXCL4 in the Human Endometrium During Menstruation to Enable Efficient Endometrial Repair.

    Science.gov (United States)

    Maybin, Jacqueline A; Thiruchelvam, Uma; Madhra, Mayank; Saunders, Philippa T K; Critchley, Hilary O D

    2017-06-01

    Repair of the endometrial surface at menstruation must be efficient to minimize blood loss and optimize reproductive function. The mechanism and regulation of endometrial repair remain undefined. To determine the presence/regulation of CXCL4 in the human endometrium as a putative repair factor at menses. Endometrial tissue was collected throughout the menstrual cycle from healthy women attending the gynecology department. Menstrual blood loss was objectively measured in a subset, and heavy menstrual bleeding (HMB) was defined as >80 mL per cycle. Monocytes were isolated from peripheral blood. CXCL4 messenger RNA (mRNA) and protein were identified by quantitative reverse transcription polymerase chain reaction and immunohistochemistry. The function/regulation of endometrial CXCL4 was explored by in vitro cell culture. CXCL4 mRNA concentrations were significantly increased during menstruation. Intense staining for CXCL4 was detected in late secretory and menstrual tissue, localized to stromal, epithelial and endothelial cells. Colocalization identified positive staining in CD68+ macrophages. Treatment of human endometrial stromal and endothelial cells (hESCs and HEECs, respectively) with steroids revealed differential regulation of CXCL4. Progesterone withdrawal resulted in significant increases in CXCL4 mRNA and protein in hESCs, whereas cortisol significantly increased CXCL4 in HEECs. In women with HMB, CXCL4 was reduced in endothelial cells during the menstrual phase compared with women with normal menstrual bleeding. Cortisol-exposed macrophages displayed increased chemotaxis toward CXCL4 compared with macrophages incubated with estrogen or progesterone. These data implicate CXCL4 in endometrial repair after menses. Reduced cortisol at the time of menses may contribute to delayed endometrial repair and HMB, in part by mechanisms involving aberrant expression of CXCL4. Copyright © 2017 by the Endocrine Society

  12. The effect of stem cell factor on proliferation of human endometrial CD146+ cells

    Directory of Open Access Journals (Sweden)

    Mehri Fayazi

    2016-07-01

    Full Text Available Background: Stem cell factor (SCF is a transcriptional factor which plays crucial roles in normal proliferation, differentiation and survival in a range of stem cells. Objective: The aim of the present study was to examine the proliferation effect of different concentrations of SCF on expansion of human endometrial CD146+ cells. Materials and Methods: In this experimental study, total populations of isolated human endometrial suspensions after fourth passage were isolated by magnetic activated cell sorting (MACS into CD146+ cells. Human endometrial CD146+ cells were karyotyped and tested for the effect of SCF on proliferation of CD146+ cells, then different concentrations of 0, 12.5, 25, 50 and 100 ng/ml was carried out and mitogens-stimulated endometrial CD146+ cells proliferation was assessed by MTT assay. Results: Chromosomal analysis showed a normal metaphase spread and 46XX karyotype. The proliferation rate of endometrial CD146P + P cells in the presence of 0, 12.5, 25, 50 and 100 ng/ml SCF were 0.945±0.094, 0.962±0.151, 0.988±0.028, 1.679±0.012 and 1.129±0.145 respectively. There was a significant increase in stem/ stromal cell proliferation following in vitro treatment by 50 ng/ml than other concentrations of SCF (p=0.01. Conclusion: The present study suggests that SCF could have effect on the proliferation and cell survival of human endometrial CD146P+P cells and it has important implications for medical sciences and cell therapies

  13. Platelets are a possible regulator of human endometrial re-epithelialization during menstruation.

    Science.gov (United States)

    Suginami, Koh; Sato, Yukiyasu; Horie, Akihito; Matsumoto, Hisanori; Kyo, Satoru; Araki, Yoshihiko; Konishi, Ikuo; Fujiwara, Hiroshi

    2017-01-01

    The human endometrium periodically breaks down and regenerates. As platelets have been reported to contribute to the tissue remodeling process, we examined the possible involvement of platelets in endometrial regeneration. The distribution of extravasating platelets throughout the menstrual cycle was immunohistochemically examined using human endometrial tissues. EM-E6/E7/hTERT cells, a human endometrial epithelial cell-derived immortalized cell line, were co-cultured with platelets, and the effects of platelets on the epithelialization response of EM-E6/E7/hTERT cells were investigated by attachment and permeability assays, immunohistochemical staining, and Western blot analysis. Immunohistochemical study showed numerous extravasated platelets in the subluminar stroma during the menstrual phase. The platelets promoted the cell-to-matrigel attachment of EM-E6/E7/hTERT cells concomitantly with the phosphorylation of focal adhesion kinase. They also promoted cell-to-cell contact among EM-E6/E7/hTERT cells in parallel with E-cadherin expression. These results indicate the possible involvement of platelets in the endometrial epithelial re-epithelialization process. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. miRNA signature and Dicer requirement during human endometrial stromal decidualization in vitro.

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    Carlos Estella

    Full Text Available Decidualization is a morphological and biochemical transformation of endometrial stromal fibroblast into differentiated decidual cells, which is critical for embryo implantation and pregnancy establishment. The complex regulatory networks have been elucidated at both the transcriptome and the proteome levels, however very little is known about the post-transcriptional regulation of this process. miRNAs regulate multiple physiological pathways and their de-regulation is associated with human disorders including gynaecological conditions such as endometriosis and preeclampsia. In this study we profile the miRNAs expression throughout human endometrial stromal (hESCs decidualization and analyze the requirement of the miRNA biogenesis enzyme Dicer during this process. A total of 26 miRNAs were upregulated and 17 miRNAs downregulated in decidualized hESCs compared to non-decidualized hESCs. Three miRNAs families, miR-181, miR-183 and miR-200, are down-regulated during the decidualization process. Using miRNAs target prediction algorithms we have identified the potential targets and pathways regulated by these miRNAs. The knockdown of Dicer has a minor effect on hESCs during in vitro decidualization. We have analyzed a battery of decidualization markers such as cell morphology, Prolactin, IGFBP-1, MPIF-1 and TIMP-3 secretion as well as HOXA10, COX2, SP1, C/EBPß and FOXO1 expression in decidualized hESCs with decreased Dicer function. We found decreased levels of HOXA10 and altered intracellular organization of actin filaments in Dicer knockdown decidualized hESCs compared to control. Our results provide the miRNA signature of hESC during the decidualization process in vitro. We also provide the first functional characterization of Dicer during human endometrial decidualization although surprisingly we found that Dicer plays a minor role regulating this process suggesting that alternative biogenesis miRNAs pathways must be involved in human

  15. Human amniotic mesenchymal stromal cell transplantation improves endometrial regeneration in rodent models of intrauterine adhesions.

    Science.gov (United States)

    Gan, Lu; Duan, Hua; Xu, Qian; Tang, Yi-Qun; Li, Jin-Jiao; Sun, Fu-Qing; Wang, Sha

    2017-05-01

    Intrauterine adhesion (IUA) is a common uterine cavity disease characterized by the unsatisfactory regeneration of damaged endometria. Recently, stem cell transplantation has been proposed to promote the recovery process. Here we investigated whether human amniotic mesenchymal stromal cells (hAMSCs), a valuable resource for transplantation therapy, could improve endometrial regeneration in rodent IUA models. Forty female Sprague-Dawley rats were randomly assigned to five groups: normal, sham-operated, mechanical injury, hAMSC transplantation, and negative control group. One week after intervention and transplantation, histological analyses were performed, and immunofluorescent and immunohistochemical expression of cell-specific markers and messenger RNA expression of cytokines were measured. Thicker endometria, increased gland numbers and fewer fibrotic areas were found in the hAMSC transplantation group compared with the mechanical injury group. Engraftment of hAMSCs was detected by the presence of anti-human nuclear antigen-positive cells in the endometrial glands of the transplantation uteri. Transplantation of hAMSCs significantly decreased messenger RNA levels of pro-inflammatory cytokines (tumor necrosis factor-α and interleukin-1β), and increased those of anti-inflammatory cytokines (basic fibroblast growth factor, and interleukin-6) compared with the injured uterine horns. Immunohistochemical expression of endometrial epithelial cells was revealed in specimens after hAMSC transplantation, whereas it was absent in the mechanically injured uteri. hAMSC transplantation promotes endometrial regeneration after injury in IUA rat models, possibly due to immunomodulatory properties. These cells provide a more easily accessible source of stem cells for future research into the impact of cell transplantation on damaged endometria. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  16. [Mifepristone inhibites the migration of endometrial cancer cells through regulating H19 methylation].

    Science.gov (United States)

    Lu, Z Z; Yan, L; Zhang, H; Li, M J; Zhang, X H; Zhao, X X

    2016-06-23

    To investigate the effect and mechanism of mifepristone on the migration of human endometrial carcinoma cells. A human endometrial carcinoma cell line, Ishikawa cells, was cultured in vitro and treated with mifepristone at different concentrations. Wound healing assay was applied to detect the migration of Ishikawa cells. RT-PCR and methylation-specific PCR (MSP) were used to detect the levels of H19 mRNA and its DNA methylation. Western-blot was used to detect the expressions of HMGA2 and epithelial to mesenchymal transition (EMT) related proteins. When treated with different concentrations of mifepristone for 48 hours, the width of scratch of the the control group, the 5 mg/L and the 10 mg/L mifepristone treatment groups were (4.18±0.07)mm, (4.68±0.07)mm, and(4.99±0.07)mm, respectively (Pendometrial carcinoma cells partially through methylation-induced of transcriptional inhibition of H19, which results in the down-regulation of HMGA2 and vimentin and upregulation of E-cadherin.

  17. Effect of Adding Human Chorionic Gonadotropin to The Endometrial Preparation Protocol in Frozen Embryo Transfer Cycles

    Directory of Open Access Journals (Sweden)

    Maryam Eftekhar

    2012-01-01

    Full Text Available Background: Human chorionic gonadotropin (HCG, one of the initial embryonic signals, isprobably a major regulator of the embryo-endometrial relationship. This study aims to assess theadvantage of HCG supplementation during the secretory phase of hormonally prepared cycles forthe transfer of cryopreserved-thawed embryos.Materials and Methods: This study was a randomized clinical trial. Infertile women who werecandidates for frozen-thawed embryo transfers entered the study and were divided into two groups,HCG and control. The endometrial preparation method was similar in both groups: all women receivedestradiol valerate (6 mg po per day from the second day of the menstrual cycle and progesteronein oil (100 mg intramuscular (I.M. when the endometrial thickness reached 8 mm. Estradiol andprogesterone were continued until the tenth week of gestation. In the HCG group, patients received anHCG 5000 IU injection on the first day of progesterone administration and the day of embryo transfer.Results: In this study, 130 couples participated: 65 in the HCG group and 65 in the control group.There was no statistically significant difference between groups regarding basic characteristics.Implantation rate, chemical pregnancy, clinical pregnancy, ongoing pregnancy, and abortion rateswere similar in both groups.Conclusion: Although HCG has some advantages in assisted reproductive technology (ARTcycles, our study did not show any benefit of HCG supplementation during the secretory phase offrozen cycles (Registration Number: IRCT201107266420N4.

  18. Anti-Proliferative Effects of Siegesbeckia orientalis Ethanol Extract on Human Endometrial RL-95 Cancer Cells

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    Chi-Chang Chang

    2014-12-01

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

  19. Sildenafil Effect on Nitric Oxide Secretion by Normal Human Endometrial Epithelial Cells Cultured In vitro

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    Farzaneh Chobsaz

    2011-01-01

    Full Text Available Background: Sildenafil is a selective inhibitor of cyclic-guanosine monphosphat-specificphosphodiesterase type 5. It increases intracellular nitric oxide (NO production in some cells.There are reports on its positive effect on uterine circulation, endometrial thickness, and infertilityimprovement. Endometrial epithelial cells (EEC play an important role in embryo attachment andimplantation. The present work investigates the effect of sildenafil on human EEC and their NOsecretion in vitro.Materials and Methods: In this experimental in vitro study, endometrial biopsies (n=10 werewashed in a phosphate buffered solution (PBS and digested with collagenase I (2 mg/ml in DMEM/F12 medium at 37°C for 90 minutes. Epithelial glands were collected by sequential filtrationthrough nylon meshes (70 and 40 μm pores, respectively. Epithelial glands were then treated withtrypsin to obtain individual cells. The cells were counted and divided into four groups: control and1, 10, and 20 μM sildenafil concentrations. Cells were cultured for 15 days at 37ºC and 5% CO2; themedia were changed every 3 days, and their supernatants were collected for the NO assay. NO wasmeasured by standard Greiss methods. Data were analyzed by one way ANOVA.Results: There was no significant difference between groups in cell count and NO secretion, but thelevel of NO increased slightly in the experimental groups. The 10 μM dose showed the highest cellcount. EEC morphology changed into long spindle cells in the case groups.Conclusion: Sildenafil (1, 10, and 20 μM showed a mild proliferative effect on human EECnumbers, but no significant change was seen in NO production.

  20. The genomic response of Ishikawa cells to bisphenol A exposure is dose- and time-dependent

    International Nuclear Information System (INIS)

    Naciff, Jorge M.; Khambatta, Zubin S.; Reichling, Timothy D.; Carr, Gregory J.; Tiesman, Jay P.; Singleton, David W.; Khan, Sohaib A.; Daston, George P.

    2010-01-01

    A reliable in vitro model to determine the potential estrogenic activity of chemicals of interest is still unavailable. To further investigate the usefulness of a human-derived cell line, we determined the transcriptional changes induced by bisphenol A (BPA) in Ishikawa cells at various doses (1 nM, 100 nM, 10 μM, and 100 μM) and time points (8, 24 and 48 h) by comparing the response of approximately 38,500 human genes and ESTs between treatment groups and controls (vehicle-treated). By trend analysis, we determined that the expression of 2794 genes was modified by BPA in a dose- and time-dependent manner (p ≤ 0.0001). However, the majority of gene expression changes induced in Ishikawa cells were elicited by the highest doses of BPA evaluated (10-100 μM), while the genomic response of the cells exposed to low doses of BPA was essentially negligible. By comparing the Ishikawa cells' response to BPA vs.17α-ethynyl estradiol we determined that the change in the expression of 307 genes was identical in the direction of the change, although the magnitude of the change for some genes was different. Further, the response of Ishikawa cells to high doses of BPA shared similarities to the estrogenic response of the rat uterus, specifically, 362 genes were regulated in a similar manner in vivo as well as in vitro. Gene ontology analysis indicated that BPA results in changes to multiple molecular pathways affecting various biological processes particularly associated with cell organization and biogenesis, regulation of translation, cell proliferation, and intracellular transport; processes also affected by estrogen exposure in the uterus of the rat. These results indicate that Ishikawa cells are capable of generating a biologically relevant estrogenic response after exposure to chemicals with varied estrogenic activity, and offer an in vitro model to assess this mode of action.

  1. Leukemia inhibitory factor increases the proliferation of human endometrial stromal cells and expression of genes related to pluripotency

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    Mojdeh Salehnia

    2017-08-01

    Full Text Available Background: Concerning the low population of human endometrial mesenchymal cells within the tissue and their potential application in the clinic and tissue engineering, some researches have been focused on their in vitro expansion. Objective: The aim of this study was to evaluate the effect of leukemia inhibitory factor (LIF as a proliferative factor on the expansion and proliferation of human endometrial stromal cells. Materials and Methods: In this experimental study, the isolated and cultured human endometrial stromal cells from women at ovulatory phase aged 20-35 years, after fourth passage were divided into control and LIF-treated groups. In the experimental group, the endometrial cells were treated by 10 ng/ml LIF in culture media and the cultured cells without adding LIF considered as control group. Both groups were evaluated and compared for proliferation rate using MTT assay, for CD90 marker by flow cytometric analysis and for the expression of Oct4, Nanog, PCNA and LIFr genes using real-time RT-PCR. Results: The proliferation rate of control and LIF-treated groups were 1.17±0.17 and 1.61±0.06 respectively and there was a significant increase in endometrial stromal cell proliferation following in vitro treatment by LIF compared to control group (p=0.049. The rate of CD90 positive cells was significantly increased in LIFtreated group (98.96±0.37% compared to control group (94.26±0.08% (p=0.0498. Also, the expression ratio of all studied genes was significantly increased in the LIFtreated group compared to control group (p=0.0479. Conclusion: The present study showed that LIF has a great impact on proliferation, survival, and maintenance of pluripotency of human endometrial stromal cells and it could be applicable in cell therapies.

  2. FOXP1 forkhead transcription factor is associated with the pathogenesis of endometrial cancer

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    Makito Mizunuma

    2016-05-01

    Full Text Available Endometrial cancers are mostly estrogen-dependent. FOXP1 is a P subfamily of forkhead box (FOX, and known as an estrogen-responsive transcription factor. The aims of this study were to examine histological location of FOXP1 in normal and malignant endometrium, and to investigate a possible association between FOXP1 and other factors considered to be involved in pathogenesis of endometrial cancer. The levels of FOXP1, estrogen receptor (ERα, and ERβ expression were examined immunohistochemically in normal and malignant endometrium obtained from 75 women (8 normal, 8 atypical endometrial hyperplasia, and 59 endometrial cancers from grade 1 to 3. The effects of estrogen on ERα, FOXP1, KRAS, and PTEN expression were analyzed in telomerase-immortalized human endometrial stromal cells (T HESCs by Western blotting. Western blotting was also used to examine the effect of FOXP1 plasmid DNA or siRNA transfection on KRAS and PTEN expression in Ishikawa cells (well differentiated endometrioid adenocarcinoma, HEC-50B cells (poorly differentiated endometrioid adenocarcinoma, and T HESCs, respectively. FOXP1 was expressed in normal and malignant endometrium, but the rate of expression was different depending upon menstrual cycle and pathological grade of malignancy. FOXP1 expression in nucleus and cytoplasm of grade 3 endometrioid cancers was significantly lower than that of grade 1 and 2 ones. Estradiol increased levels of FOXP1 and KRAS expression in a dose- and time-dependent manner in T HESCs cells, and FOXP1 transfection or knockdown led to increase or decrease of KRAS expression but not PTEN. KRAS expression level was significantly related to FOXP1 and ERα levels in cancer tissues. Estradiol did not affect KRAS expression in T HESCs cells transfected with FOXP1 siRNA. These results suggest that FOXP1 is involved in estrogen dependent endometrial cancers through KRAS pathway.

  3. Normal endometrial stromal cells regulate 17β-estradiol-induced epithelial-mesenchymal transition via slug and E-cadherin in endometrial adenocarcinoma cells in vitro.

    Science.gov (United States)

    Zhang, Hui; Li, Hongyan; Qi, Shasha; Liu, Zhao; Fu, Yibing; Li, Mingjiang; Zhao, Xingbo

    2017-01-01

    Stroma-tumor communication participates in the pathogenesis of endometrial carcinomas. In previous studies, we found that normal stromal cells inhibited the growth of endometrial carcinoma cells. Here, we investigated the role of normal stromal cells in the epithelial-mesenchymal transition (EMT) of endometrial carcinoma cells and explored the possible mechanism implied. We found that conditioned medium (CM) by normal endometrial stromal cells (NSC) reduced cell growth and induced cell apoptosis in Ishikawa cells. CM by NSC inhibited 17β-estradiol-induced cell growth and apoptosis decrease in Ishikawa cells. Moreover, CM by NSC inhibited the migration and invasion, and 17β-estradiol-induced migration and invasion in Ishikawa cells. Meanwhile, CM by NSC decreased Slug expression and 17β-estradiol-induced Slug expression, increased E-cadherin expression and abolished 17β-estradiol-induced E-cadherin reduction in Ishikawa cells. In conclusion, normal stromal factors can inhibit 17β-estradiol-induced cell proliferation and apoptosis inhibition, and abolished 17β-estradiol-induced EMT in endometrial cancer cell via regulating E-cadherin and Slug expression.

  4. Decidualized Human Endometrial Stromal Cells Mediate Hemostasis, Angiogenesis, and Abnormal Uterine Bleeding

    Science.gov (United States)

    Lockwood, Charles J.; Krikun, Graciela; Hickey, Martha; Huang, S. Joseph; Schatz, Frederick

    2011-01-01

    Factor VII binds trans-membrane tissue factor to initiate hemostasis by forming thrombin. Tissue factor expression is enhanced in decidualized human endometrial stromal cells during the luteal phase. Long-term progestin only contraceptives elicit: 1) abnormal uterine bleeding from fragile vessels at focal bleeding sites, 2) paradoxically high tissue factor expression at bleeding sites; 3) reduced endometrial blood flow promoting local hypoxia and enhancing reactive oxygen species levels; and 4) aberrant angiogenesis reflecting increased stromal cell-expressed vascular endothelial growth factor, decreased Angiopoietin-1 and increased endothelial cell-expressed Angiopoietin-2. Aberrantly high local vascular permeability enhances circulating factor VII to decidualized stromal cell-expressed tissue factor to generate excess thrombin. Hypoxia-thrombin interactions augment expression of vascular endothelial growth factor and interleukin-8 by stromal cells. Thrombin, vascular endothelial growth factor and interlerukin-8 synergis-tically augment angiogenesis in a milieu of reactive oxygen species-induced endothelial cell activation. The resulting enhanced vessel fragility promotes abnormal uterine bleeding. PMID:19208784

  5. Establishment and characterization of a human uterine endometrial undifferentiated carcinoma cell line, TMG-L.

    Science.gov (United States)

    Hasegawa, Kiyoshi; Suzuki, Machiko; Ishikawa, Kunimi; Yasue, Akira; Kato, Rina; Nakamura, Azumi; Kuroki, Jun; Udagawa, Yasuhiro

    2003-03-01

    A new cell line of human uterine endometrial undifferentiated carcinoma, designated as TMG-L, was established from the metastatic lymph node of 56-year-old patient TMG-L cells have been cultured with Ham's F-12 medium supplemented with 10% FCS and grew as a loosely adherent monolayer with polygonal or spindle-shaped cells exhibiting poor cell-cell contact and piled up against each other, showing a tendency to grow as floating cells. The doubling time of this cell line was about 48 hours, and chromosomal analysis revealed aneuploidy at passage 25. The cells formed tumors in SCID mouse, the histology of which was similar to that of undifferentiated carcinoma component of primary tumor. TMG-L cells showed the loss of expression and membranous localization of either E-cadherin or alpha-catenin, implied corresponding loss of their adhesive function. And this dysfunction implicated the biological aggressive behavior of uterine endometrial undifferentiated carcinoma. This cell line appears to provide a useful system for studying uterine undifferentiated carcinoma in vivo and in vitro.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Chun-E Ren

    2015-03-01

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

  8. Thrombin impairs human endometrial endothelial angiogenesis; implications for progestin-only contraceptive-induced abnormal uterine bleeding.

    Science.gov (United States)

    Shapiro, John P; Guzeloglu-Kayisli, Ozlem; Kayisli, Umit A; Semerci, Nihan; Huang, S Joseph; Arlier, Sefa; Larsen, Kellie; Fadda, Paolo; Schatz, Frederick; Lockwood, Charles J

    2017-06-01

    Progestin-only contraceptives induce abnormal uterine bleeding, accompanied by prothrombin leakage from dilated endometrial microvessels and increased thrombin generation by human endometrial stromal cell (HESC)-expressed tissue factor. Initial studies of the thrombin-treated HESC secretome identified elevated levels of cleaved chondroitin sulfate proteoglycan 4 (CSPG4), impairing pericyte-endothelial interactions. Thus, we investigated direct and CSPG4-mediated effects of thrombin in eliciting abnormal uterine bleeding by disrupting endometrial angiogenesis. Liquid chromatography/tandem mass spectrometry, enzyme-linked immunosorbent assay (ELISA) and quantitative real-time-polymerase chain reaction (PCR) evaluated conditioned medium supernatant and cell lysates from control versus thrombin-treated HESCs. Pre- and post-Depo medroxyprogesterone acetate (DMPA)-administered endometria were immunostained for CSPG4. Proliferation, apoptosis and tube formation were assessed in human endometrial endothelial cells (HEECs) incubated with recombinant human (rh)-CSPG4 or thrombin or both. Thrombin induced CSPG4 protein expression in cultured HESCs as detected by mass spectrometry and ELISA (pabnormal uterine bleeding in DMPA users. Mass spectrometry analysis identified several HESC-secreted proteins regulated by thrombin. Therapeutic agents blocking angiogenic effects of thrombin in HESCs can prevent or minimize progestin-only contraceptive-induced abnormal uterine bleeding. Copyright © 2017. Published by Elsevier Inc.

  9. Strong convergence of modified Ishikawa iterations for nonlinear ...

    Indian Academy of Sciences (India)

    interval [0, 1]. The second iteration process is referred to as Ishikawa's iteration process [11] which is .... Let E be a smooth Banach space with dual E∗ ..... and applications, in: Theory and Applications of Nonlinear Operators of Accretive and.

  10. Development of organoids from mouse and human endometrium showing endometrial epithelium physiology and long-term expandability.

    Science.gov (United States)

    Boretto, Matteo; Cox, Benoit; Noben, Manuel; Hendriks, Nikolai; Fassbender, Amelie; Roose, Heleen; Amant, Frédéric; Timmerman, Dirk; Tomassetti, Carla; Vanhie, Arne; Meuleman, Christel; Ferrante, Marc; Vankelecom, Hugo

    2017-05-15

    The endometrium, which is of crucial importance for reproduction, undergoes dynamic cyclic tissue remodeling. Knowledge of its molecular and cellular regulation is poor, primarily owing to a lack of study models. Here, we have established a novel and promising organoid model from both mouse and human endometrium. Dissociated endometrial tissue, embedded in Matrigel under WNT-activating conditions, swiftly formed organoid structures that showed long-term expansion capacity, and reproduced the molecular and histological phenotype of the tissue's epithelium. The supplemented WNT level determined the type of mouse endometrial organoids obtained: high WNT yielded cystic organoids displaying a more differentiated phenotype than the dense organoids obtained in low WNT. The organoids phenocopied physiological responses of endometrial epithelium to hormones, including increased cell proliferation under estrogen and maturation upon progesterone. Moreover, the human endometrial organoids replicated the menstrual cycle under hormonal treatment at both the morpho-histological and molecular levels. Together, we established an organoid culture system for endometrium, reproducing tissue epithelium physiology and allowing long-term expansion. This novel model provides a powerful tool for studying mechanisms underlying the biology as well as the pathology of this key reproductive organ. © 2017. Published by The Company of Biologists Ltd.

  11. Biological characteristics of human menstrual blood-derived endometrial stem cells.

    Science.gov (United States)

    Liu, Yanli; Niu, Rongcheng; Yang, Fen; Yan, Yan; Liang, Shengying; Sun, Yuliang; Shen, Ping; Lin, Juntang

    2018-03-01

    Successful isolation of human endometrial stem cells from menstrual blood, namely menstrual blood-derived endometrial stem cells (MenSCs), has provided enticing alternative seed cells for stem cell-based therapy. MenSCs are enriched in the self-regenerative tissue, endometrium, which shed along the periodic menstrual blood and thus their acquisition involves no physical invasiveness. However, the impact of the storage duration of menstrual blood prior to stem cell isolation, the age of the donor, the number of passages on the self-renewing of MenSCs, the paracrine production of biological factors in MenSCs and expression of adhesion molecules on MenSCs remain elusive. In this study, we confirmed that MenSCs reside in shedding endometrium, and documented that up to 3 days of storage at 4°C has little impact on MenSCs, while the age of the donor and the number of passages are negatively associated with proliferation capacity of MenSCs. Moreover, we found that MenSCs were actually immune-privileged and projected no risk of tumour formation. Also, we documented a lung- and liver-dominated, spleen- and kidney-involved organic distribution profile of MenSC 3 days after intravenous transfer into mice. At last, we suggested that MenSCs may have potentially therapeutic effects on diseases through paracrine effect and immunomodulation. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  12. Reduced homeobox protein MSX1 in human endometrial tissue is linked to infertility.

    Science.gov (United States)

    Bolnick, Alan D; Bolnick, Jay M; Kilburn, Brian A; Stewart, Tamika; Oakes, Jonathan; Rodriguez-Kovacs, Javier; Kohan-Ghadr, Hamid-Reza; Dai, Jing; Diamond, Michael P; Hirota, Yasushi; Drewlo, Sascha; Dey, Sudhansu K; Armant, D Randall

    2016-09-01

    Is protein expression of the muscle segment homeobox gene family member MSX1 altered in the human secretory endometrium by cell type, developmental stage or fertility? MSX1 protein levels, normally elevated in the secretory phase endometrium, were significantly reduced in endometrial biopsies obtained from women of infertile couples. Molecular changes in the endometrium are important for fertility in both animals and humans. Msx1 is expressed in the preimplantation mouse uterus and regulates uterine receptivity for implantation. The MSX protein persists a short time, after its message has been down-regulated. Microarray analysis of the human endometrium reveals a similar pattern of MSX1 mRNA expression that peaks before the receptive period, with depressed expression at implantation. Targeted deletion of uterine Msx1 and Msx2 in mice prevents the loss of epithelial cell polarity during implantation and causes infertility. MSX1 mRNA and cell type-specific levels of MSX1 protein were quantified from two retrospective cohorts during the human endometrial cycle. MSX1 protein expression patterns were compared between fertile and infertile couples. Selected samples were dual-labeled by immunofluorescence microscopy to localize E-cadherin and β-catenin in epithelial cells. MSX1 mRNA was quantified by PCR in endometrium from hysterectomies (n = 14) determined by endometrial dating to be in the late-proliferative (cycle days 10-13), early-secretory (cycle days 14-19) or mid-secretory (cycle days 20-24) phase. MSX1 protein was localized using high-throughput, semi-quantitative immunohistochemistry with sectioned endometrial biopsy tissues from fertile (n = 89) and infertile (n = 89) couples. Image analysis measured stain intensity specifically within the luminal epithelium, glands and stroma during the early-, mid- and late- (cycle days 25-28) secretory phases. MSX1 transcript increased 5-fold (P MSX1 protein displayed strong nuclear localization in the luminal epithelium

  13. Derivation of Insulin Producing Cells From Human Endometrial Stromal Stem Cells and Use in the Treatment of Murine Diabetes

    OpenAIRE

    Santamaria, Xavier; Massasa, Efi E; Feng, Yuzhe; Wolff, Erin; Taylor, Hugh S

    2011-01-01

    Pancreatic islet cell transplantation is an effective approach to treat type 1 diabetes, however the shortage of cadaveric donors and limitations due to rejection require alternative solutions. Multipotent cells derived from the uterine endometrium have the ability to differentiate into mesodermal and ectodermal cellular lineages, suggesting the existence of mesenchymal stem cells in this tissue. We differentiated human endometrial stromal stem cells (ESSC) into insulin secreting cells using ...

  14. Metformin inhibits 17?-estradiol-induced epithelial-to-mesenchymal transition via ?Klotho-related ERK1/2 signaling and AMPK? signaling in endometrial adenocarcinoma cells

    OpenAIRE

    Liu, Zhao; Qi, Shasha; Zhao, Xingbo; Li, Mingjiang; Ding, Sentai; Lu, Jiaju; Zhang, Hui

    2016-01-01

    The potential role of metformin in treating endometrial cancer remains to be explored. The current study investigated the role of metformin in 17?-estradiol-induced epithelial-mesenchymal transition (EMT) in endometrial adenocarcinoma cells. We found that 17?-estradiol promoted proliferation and migration, attenuated apoptosis in both estrogen receptor (ER) positive and ER negative endometrial adenocarcinoma cells (Ishikawa and KLE cells, respectively). Metformin abolished 17?-estradiol-induc...

  15. An inhibitor of K+ channels modulates human endometrial tumor-initiating cells

    Directory of Open Access Journals (Sweden)

    Leslie Kimberly K

    2011-08-01

    Full Text Available Abstract Background Many potassium ion (K+ channels function as oncogenes to sustain growth of solid tumors, but their role in cancer progression is not well understood. Emerging evidence suggests that the early progenitor cancer cell subpopulation, termed tumor initiating cells (TIC, are critical to cancer progression. Results A non-selective antagonist of multiple types of K+ channels, tetraethylammonium (TEA, was found to suppress colony formation in endometrial cancer cells via inhibition of putative TIC. The data also indicated that withdrawal of TEA results in a significant enhancement of tumorigenesis. When the TIC-enriched subpopulation was isolated from the endometrial cancer cells, TEA was also found to inhibit growth in vitro. Conclusions These studies suggest that the activity of potassium channels significantly contributes to the progression of endometrial tumors, and the antagonists of potassium channels are candidate anti-cancer drugs to specifically target tumor initiating cells in endometrial cancer therapy.

  16. Endometrial cancer.

    Science.gov (United States)

    Porter, Stephanie

    2002-08-01

    To provide an update for nurses involved in the care of women at risk or being treated for endometrial cancer. Review articles, research reports, and medical and nursing text-books. Endometrial cancer is the most common gynecologic malignancy. Although most women with endometrial cancer present with early stage disease and have an excellent chance of cure, approximately 6,600 women in the United States are expected to die from the disease in 2002. Treatment of patients with advanced or recurrent disease remains challenging, with no proven best standard of treatment. Nursing plays an important role in prevention and early detection of endometrial cancer, patient education, patient care, and rehabilitation.

  17. Human endometrial stromal stem cells differentiate into megakaryocytes with the ability to produce functional platelets.

    Directory of Open Access Journals (Sweden)

    Jinju Wang

    Full Text Available Human endometrium is a high dynamic tissue that contains endometrial stromal stem cells (hESSCs. The hESSCs have been differentiated into a number of cell lineages. However, differentiation of hESSCs into megakaryocytes (MKs has not yet been investigated. The aim of this study was to investigate the feasibility of MK generation from hESSCs and subsequent production of functional platelets (PLTs. In our study, hESSCs were cultured from endometrial stromal cells as confirmed by positive stromal cell specific markers (CD90 and CD29 and negative hematopoietic stem cell markers (CD45 and CD34 expression. Then, hESSCs were differentiated in a medium supplemented with thrombopoietin (TPO for 18 days. The MK differentiation was analyzed by flow cytometry and confocal microscopy. The differentiation medium was collected for PLT production analysis by flow cytometry, transmission electron microscopy and functional measurements. Our results show: 1 MKs were successfully generated from hESSCs as identified by expression of specific markers (CD41a: 1 ± 0.09% and 39 ± 3.0%; CD42b: 1.2 ± 0.06% and 28 ± 2.0%, control vs. differentiation accompanied with reduction of pluripotent transcription factors (Oct4 and Sox2 expression; 2 The level of PLTs in the differentiation medium was 16 ± 1 number/µl as determined by size (2-4 µm and CD41a expression (CD41a: 1 ± 0.4% and 90±2.0%, control vs. differentiation; 3 Generated PLTs were functional as evidenced by the up-regulation of CD62p expression and fibrinogen binding following thrombin stimulation; 4 Released PLTs showed similar ultra-structure characteristics (alpha granules, vacuoles and dense tubular system as PLTs from peripheral blood determined by electron microscopic analysis. Data demonstrate the feasibility of generating MKs from hESSCs, and that the generated MKs release functional PLTs. Therefore, hESSCs could be a potential new stem cell source for in vitro MK/PLT production.

  18. Tumorigenesis of K-ras mutation in human endometrial carcinoma via upregulation of estrogen receptor.

    Science.gov (United States)

    Tu, Zheng; Gui, Liming; Wang, Jianliu; Li, Xiaoping; Sun, Pengming; Wei, Lihui

    2006-05-01

    To investigate the tumorigenesis of mutant [12Asp]-K-ras in endometrial carcinoma and its relationship with ER. We constructed pcDI-[12Asp]K-ras4B by inserting full-length [12Asp]K-ras4B from human endometrial carcinoma Hec-1A cells, into pcDI vector. Cell proliferation of NIH3T3 after transfection with pcDI-[12Asp]K-ras4B was measured by MTT assay. The cell transformation was determined by colony formation and tumor nodule development. [12Asp]-K-ras4B-NIH3T3 cells were transfected with constitutively active pCMV-RafCAAX and dominant-negative pCMV-RafS621A. Cell growth was measured by MTT assay and [3H]thymidine incorporation. After transfected with pcDI-[12Asp]K-ras4B or pCMV-RafS621A, the cells were harvested for Western blot and reporter assay to determine the expression and transcriptional activity of ERalpha and ERbeta, respectively. [12Asp]-K-ras4B enhanced NIH3T3 cells proliferation after 48 h post-transfection (P ras4B-NIH3T3 cells (13.48%) than pcDI-NIH3T3 (4.26%) or untreated NIH3T3 (2.33%). The pcDI-[12Asp]-K-ras4B-NIH3T3 cells injected to the nude mice Balb/C developed tumor nodules with poor-differentiated cells after 12 days. An increase of ERalpha and ERbeta was observed in pcDI-[12Asp]-K-ras4B-NIH3T3 cells. RafS621A downregulated ERalpha and ERbeta expression. Estrogen induced the ER transcriptional activity by 5-fold in pcDI-NIH3T3 cells, 13-fold in pcDI-[12Asp]K-ras4B-NIH3T3 and 19-fold in HEC-1A. RafS621A suppressed the ER transcriptional activity. K-ras mutation induces tumorigenesis in endometrium, and this malignant transformation involves Raf signaling pathway and ER.

  19. High-voltage irradiation of xenotransplanted human ovarial, endometrial, and cervical carcinomas

    International Nuclear Information System (INIS)

    Kleine, W.; Wrzodek, W.; Stange, S.; Ladner, H.A.

    1981-01-01

    High-voltage irradiation of four ovarial carcinomas, four endometrial carcinomas and two carcinomas of the cervix is reported on which were transplanted subcutaneously to nu/nu mice. In all cases, the growth was stopped and the tumour receded under irradiation; in 8 cases, after stopping the irradiation with a dose of 30 to 60 Gy the growth went on. Of two carcinomas with decrease in the size and a stopped growth over 20 weeks, in one case no vital cells could be found any more while in the other one there were still numerous vital cells. These showed also after irradiation an unchanged radionucleotid incorporation in the single cell suspension. The effect of a high-voltage irradiation seems to be independent on the histologic picture, but dependent on the dose and the fractioning. The incorporation rates of 3 H-thymidine and 3 H-uridine in the single cell suspension reamined inchanged both before and after irradiation. Irradiation of the xenotransplantate of one side showed the exclusively local effect of this measure. This is confirmed by comparative examinations of the same tumours with a chemotherapy. Thus the nude mouse model offers the possibility of observing the effects of a high-voltage irradiation of human tissue in vivo without involving the total organism of the tumourous animal like in chemotherapy. This shows another field for future questions with nude mice. (orig.) [de

  20. Distribution volumes of macromolecules in human ovarian and endometrial cancers--effects of extracellular matrix structure.

    Science.gov (United States)

    Haslene-Hox, Hanne; Oveland, Eystein; Woie, Kathrine; Salvesen, Helga B; Tenstad, Olav; Wiig, Helge

    2015-01-01

    Elements of the extracellular matrix (ECM), notably collagen and glucosaminoglycans, will restrict part of the space available for soluble macromolecules simply because the molecules cannot occupy the same space. This phenomenon may influence macromolecular drug uptake. To study the influence of steric and charge effects of the ECM on the distribution volumes of macromolecules in human healthy and malignant gynecologic tissues we used as probes 15 abundant plasma proteins quantified by high-resolution mass spectrometry. The available distribution volume (VA) of albumin was increased in ovarian carcinoma compared with healthy ovarian tissue. Furthermore, VA of plasma proteins between 40 and 190 kDa decreased with size for endometrial carcinoma and healthy ovarian tissue, but was independent of molecular weight for the ovarian carcinomas. An effect of charge on distribution volume was only found in healthy ovaries, which had lower hydration and high collagen content, indicating that a condensed interstitium increases the influence of negative charges. A number of earlier suggested biomarker candidates were detected in increased amounts in malignant tissue, e.g., stathmin and spindlin-1, showing that interstitial fluid, even when unfractionated, can be a valuable source for tissue-specific proteins. We demonstrate that the distribution of abundant plasma proteins in the interstitium can be elucidated by mass spectrometry methods and depends markedly on hydration and ECM structure. Our data can be used in modeling of drug uptake, and give indications on ECM components to be targeted to increase the uptake of macromolecular substances. Copyright © 2015 the American Physiological Society.

  1. A new model of Ishikawa diagram for quality assessment

    Science.gov (United States)

    Liliana, Luca

    2016-11-01

    The paper presents the results of a study concerning the use of the Ishikawa diagram in analyzing the causes that determine errors in the evaluation of theparts precision in the machine construction field. The studied problem was"errors in the evaluation of partsprecision” and this constitutes the head of the Ishikawa diagram skeleton.All the possible, main and secondary causes that could generate the studied problem were identified. The most known Ishikawa models are 4M, 5M, 6M, the initials being in order: materials, methods, man, machines, mother nature, measurement. The paper shows the potential causes of the studied problem, which were firstly grouped in three categories, as follows: causes that lead to errors in assessing the dimensional accuracy, causes that determine errors in the evaluation of shape and position abnormalities and causes for errors in roughness evaluation. We took into account the main components of parts precision in the machine construction field. For each of the three categories of causes there were distributed potential secondary causes on groups of M (man, methods, machines, materials, environment/ medio ambiente-sp.). We opted for a new model of Ishikawa diagram, resulting from the composition of three fish skeletons corresponding to the main categories of parts accuracy.

  2. Negative Effect of Ellagic Acid on Cytosolic pH Regulation and Glycolytic Flux in Human Endometrial Cancer Cells.

    Science.gov (United States)

    Abdelazeem, Khalid N M; Singh, Yogesh; Lang, Florian; Salker, Madhuri S

    2017-01-01

    Key properties of tumor cells include enhanced glycolytic flux with excessive consumption of glucose and formation of lactate. As glycolysis is highly sensitive to cytosolic pH, maintenance of glycolysis requires export of H+ ions, which is in part accomplished by Na+/H+ exchangers, such as NHE1. The carrier is sensitive to oxidative stress. Growth of tumor cells could be suppressed by the polyphenol Ellagic acid, which is found in various fruits and vegetables. An effect of Ellagic acid on transport processes has, however, never been reported. The present study thus elucidated an effect of Ellagic acid on cytosolic pH (pHi), NHE1 transcript levels, NHE1 protein abundance, Na+/H+ exchanger activity, and lactate release. Experiments were performed in Ishikawa cells without or with prior Ellagic acid (20 µM) treatment. NHE1 transcript levels were determined by qRT-PCR, NHE1 protein abundance by Western blotting, pHi utilizing (2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein [BCECF] fluorescence, Na+/H+ exchanger activity from Na+ dependent realkalinization after an ammonium pulse, cell volume from forward scatter in flow cytometry, reactive oxygen species (ROS) from 2',7'-dichlorodihydrofluorescein fluorescence, glucose uptake utilizing 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose, and lactate concentration in the supernatant utilizing a colorimetric (570 nm)/ fluorometric enzymatic assay. A 48 hour treatment with Ellagic acid (20 µM) significantly decreased NHE1 transcript levels by 75%, NHE1 protein abundance by 95%, pHi from 7.24 ± 0.01 to 7.02 ± 0.01, Na+/H+ exchanger activity by 77%, forward scatter by 10%, ROS by 82%, glucose uptake by 58%, and lactate release by 15%. Ellagic acid (20µM) markedly down-regulates ROS formation and NHE1 expression leading to decreased Na+/H+ exchanger activity, pHi, glucose uptake and lactate release in endometrial cancer cells. Those effects presumably contribute to reprogramming and growth

  3. Negative Effect of Ellagic Acid on Cytosolic pH Regulation and Glycolytic Flux in Human Endometrial Cancer Cells

    Directory of Open Access Journals (Sweden)

    Khalid N. M. Abdelazeem

    2017-04-01

    Full Text Available Background/Aims: Key properties of tumor cells include enhanced glycolytic flux with excessive consumption of glucose and formation of lactate. As glycolysis is highly sensitive to cytosolic pH, maintenance of glycolysis requires export of H+ ions, which is in part accomplished by Na+/H+ exchangers, such as NHE1. The carrier is sensitive to oxidative stress. Growth of tumor cells could be suppressed by the polyphenol Ellagic acid, which is found in various fruits and vegetables. An effect of Ellagic acid on transport processes has, however, never been reported. The present study thus elucidated an effect of Ellagic acid on cytosolic pH (pHi, NHE1 transcript levels, NHE1 protein abundance, Na+/H+ exchanger activity, and lactate release. Methods: Experiments were performed in Ishikawa cells without or with prior Ellagic acid (20 µM treatment. NHE1 transcript levels were determined by qRT-PCR, NHE1 protein abundance by Western blotting, pHi utilizing (2',7'-bis-(2-carboxyethyl-5-(and-6-carboxyfluorescein [BCECF] fluorescence, Na+/H+ exchanger activity from Na+ dependent realkalinization after an ammonium pulse, cell volume from forward scatter in flow cytometry, reactive oxygen species (ROS from 2’,7’-dichlorodihydrofluorescein fluorescence, glucose uptake utilizing 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-ylamino-2-deoxyglucose, and lactate concentration in the supernatant utilizing a colorimetric (570 nm/ fluorometric enzymatic assay. Results: A 48 hour treatment with Ellagic acid (20 µM significantly decreased NHE1 transcript levels by 75%, NHE1 protein abundance by 95%, pHi from 7.24 ± 0.01 to 7.02 ± 0.01, Na+/H+ exchanger activity by 77%, forward scatter by 10%, ROS by 82%, glucose uptake by 58%, and lactate release by 15%. Conclusion: Ellagic acid (20µM markedly down-regulates ROS formation and NHE1 expression leading to decreased Na+/H+ exchanger activity, pHi, glucose uptake and lactate release in endometrial cancer cells. Those

  4. Gene expression changes induced by estrogen and selective estrogen receptor modulators in primary-cultured human endometrial cells: signals that distinguish the human carcinogen tamoxifen

    International Nuclear Information System (INIS)

    Pole, Jessica C.M.; Gold, Leslie I.; Orton, Terry; Huby, Russell; Carmichael, Paul L.

    2005-01-01

    Tamoxifen has long been the endocrine treatment of choice for women with breast cancer and is now employed for prophylactic use in women at high risk from breast cancer. Other selective estrogen receptor modulators (SERMs), such as raloxifene, mimic some of tamoxifen's beneficial effects and, like tamoxifen, exhibit a complex mixture of organ-specific estrogen agonist and antagonistic properties. However, accompanying the positive effects of tamoxifen has been the emergence of evidence for an increased risk of endometrial cancer associated with its use. A more complete understanding of the mechanism(s) of SERM carcinogenicity and endometrial effects is therefore required. We have sought to compare and characterise the transcript profile of tamoxifen, raloxifene and the agonist estradiol in human endometrial cells. Using primary cultures of human endometria, to best emulate the in vivo responses in a manageable in vitro system, we have shown 230 significant changes in gene expression for epithelial cultures and 83 in stromal cultures, either specific to 17β-estradiol, tamoxifen or raloxifene, or changed across more than one of the treatments. Considering the transcriptome as a whole, the endometrial responses to raloxifene or tamoxifen were more similar than either drug was to 17β-estradiol. Treatment of endometrial cultures with tamoxifen resulted in the largest number of gene changes relative to control cultures and a high proportion of genes associated with regulation of gene transcription, cell-cycle control and signal transduction. Tamoxifen-specific changes that might point towards mechanisms for its proliferative response in the endometrium included changes in retinoblastoma and c-myc binding proteins, the APCL, dihydrofolate reductase (DHFR) and E2F1 genes and other transcription factors. Tamoxifen was also found to give rise to the highest number of gene expression changes common to those that characterise malignant endometria. It is anticipated that this

  5. Pueraria mirifica inhibits 17β-estradiol-induced cell proliferation of human endometrial mesenchymal stem cells.

    Science.gov (United States)

    Lin, Ta-Chin; Wang, Kai-Hung; Kao, An-Pei; Chuang, Kuo-Hsiang; Kuo, Tsung-Cheng

    2017-12-01

    The notion that the human endometrium may contain a population of stem cells has recently been proposed. The mesenchymal stem cells (MSCs) in the endometrium are believed to be responsible for the remarkable regenerative ability of endometrial cells. Estrogens influence the physiological and pathological processes of several hormone-dependent tissues, such as the endometrium. Pueraria mirifica (PM) is a herbal plant that contains several phytoestrogens, including isoflavones, lignans, and coumestans, and is known to exert an estrogenic effect on animal models. The present study investigated the effects of PM on the proliferation of human endometrial MSCs (hEN-MSCs). The hEN-MSCs were isolated from human endometrial tissue. The surface markers of these hEN-MSCs were identified through reverse transcription-polymerase chain reaction analysis. The proliferation potential of hEN-MSCs was measured through a cell proliferation assay. Multilineage differentiation ability was confirmed through Oil red O and von Kossa staining. This study demonstrated that 17β-estradiol-responsive MSCs with Oct-4, CD90, and CD105 gene expression can be derived from the human endometrium and that PM exerts biological effects on hEN-MSCs, specifically, enhanced cell growth rate, through the estrogen receptor. Furthermore, PM at 1500 and 2000 μg/mL significantly increased cell proliferation compared with the vehicle control, and PM concentration at 1000 μg/mL significantly inhibited the enhanced cell growth rate induced by 17β-estradiol in hEN-MSCs. This study provides new insights into the possible biological effects of PM on the proliferation of hEN-MSCs. Copyright © 2017. Published by Elsevier B.V.

  6. Curcumin exhibits anti-tumor effect and attenuates cellular migration via Slit-2 mediated down-regulation of SDF-1 and CXCR4 in endometrial adenocarcinoma cells.

    Science.gov (United States)

    Sirohi, Vijay Kumar; Popli, Pooja; Sankhwar, Pushplata; Kaushal, Jyoti Bala; Gupta, Kanchan; Manohar, Murli; Dwivedi, Anila

    2017-06-01

    Although curcumin shows anti-proliferative and anti-inflammatory activities in various cancers, the effect of curcumin on cellular migration in endometrial adenocarcinoma cells remains to be understood. The current investigation was aimed to explore the anti-proliferative and anti-migratory effects of curcumin and its mechanism of action in endometrial cancer cells. Our in-vitro and in-vivo experimental studies showed that curcumin inhibited the proliferation of endometrial cancer cells and suppressed the tumor growth in Ishikawa xenograft mouse model. Curcumin induced ROS-mediated apoptosis in endometrial cancer cells. Curcumin suppressed the migration rate of Ishikawa and Hec-1B cells as analyzed by scratch wound assay. In transwell migration studies, knock down of Slit-2 reversed the anti-migratory effect of curcumin in these cell lines. Curcumin significantly up-regulated the expression of Slit-2 in Ishikawa, Hec-1B and primary endometrial cancer cells while it down-regulated the expression of stromal cell-derived factor-1 (SDF-1) and CXCR4 which in turn, suppressed the expression of matrix metallopeptidases (MMP) 2 and 9, thus attenuating the migration of endometrial cancer cells. In summary, we have demonstrated that curcumin has inhibitory effect on cellular migration via Slit-2 mediated down-regulation of CXCR4, SDF-1, and MMP2/MMP9 in endometrial carcinoma cells. These findings helped explore the role of Slit-2 in endometrial cancer cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Regulation of matriptase and HAI-1 system, a novel therapeutic target in human endometrial cancer cells.

    Science.gov (United States)

    Sun, Pengming; Xue, Lifang; Song, Yiyi; Mao, Xiaodan; Chen, Lili; Dong, Binhua; Braicu, Elena Loana; Sehouli, Jalid

    2018-02-27

    The effects of specific and non-specific regulation of matriptase on endometrial cancer cells in vitro were investigated. Messenger ribonucleic acid (mRNA) and protein expression of matriptase and hepatocyte growth factor activator inhibitor-1 (HAI-1) in RL-952, HEC-1A, and HEC-1B endometrial cancer cells were detected by real-time quantitative PCR (RT-qPCR) and western blot. The cells were infected with lentivirus-mediated small-interfering RNA (siRNA) targeted on matriptase (MA-siRNA) or treated with different cisplatin (DDP) concentrations. After treatment, invasion, migration, and cellular apoptosis were analyzed. Matriptase mRNA and protein expression significantly decreased to 80% after infection with MA-siRNA ( P scratch and trans-well chamber assays showed significant inhibition of invasiveness and metastasis. Upon incubation with cisplatin at concentrations higher than the therapeutic dose for 24 h, the expressions of matriptase and HAI-1 significantly decreased ( P endometrial cancer cells were significantly decreased ( P endometrial cancer cells showed promising therapeutic features.

  8. Endometrial Cancer

    Science.gov (United States)

    ... thick and show changes that look like cancer. Abnormal uterine bleeding is a common sign of EIN. Diagnosis and ... The most common symptom of endometrial cancer is abnormal uterine bleeding. For women who are premenopausal, this includes irregular ...

  9. Endometrial Hyperplasia

    Science.gov (United States)

    ... hyperplasia? The most common sign of hyperplasia is abnormal uterine bleeding. If you have any of the following, you ... endometrial hyperplasia diagnosed? There are many causes of abnormal uterine bleeding. If you have abnormal bleeding and you are ...

  10. Emodin enhances the chemosensitivity of endometrial cancer by inhibiting ROS-mediated Cisplatin-resistance.

    Science.gov (United States)

    Ding, Ning; Zhang, Hong; Su, Shan; Ding, Yumei; Yu, Xiaohui; Tang, Yujie; Wang, Qingfang; Liu, Peishu

    2017-12-18

    Background Endometrial cancer is a common cause of death in gynecological malignancies. Cisplatin is a clinically chemotherapeutic agent. However, drug-resistance is the primary cause of treatment failure. Objective Emodin is commonly used clinically to increase the sensitivity of chemotherapeutic agents, yet whether Emodin promotes the role of Cisplatin in the treatment of endometrial cancer has not been studied. Method CCK-8 kit was utilized to determine the growth of two endometrial cancer cell lines, Ishikawa and HEC-IB. The apoptosis level of Ishikawa and HEC-IB cells was detected by Annexin V / propidium iodide double-staining assay. ROS level was detected by DCFH-DA and NADPH oxidase expression. Expressions of drug-resistant genes were examined by real-time PCR and Western blotting. Results Emodin combined with Cisplatin reduced cell growth and increased the apoptosis of endometrial cancer cells. Co-treatment of Emodin and Cisplatin increased chemosensitivity by inhibiting the expression of drug-resistant genes through reducing the ROS levels in endometrial cancer cells. In an endometrial cancer xenograft murine model, the tumor size was reduced and animal survival time was increased by co-treatment of Emodin and Cisplatin. Conclusion This study demonstrates that Emodin enhances the chemosensitivity of Cisplatin on endometrial cancer by inhibiting ROS-mediated expression of drug-resistance genes. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. Endometrial imaging

    OpenAIRE

    Vassallo, Pierre

    2012-01-01

      "nAbnormal uterine bleeding, whether in peri menopausal or postmenopausal patients, is an important clinical concern and results in much medical intervention. When bleeding occurs in women over 40 years of age as well as any postmenopausal women, endometrial assessment is mandatory. In the past and present, many clinicians prefer to begin such assessment with blind endometrial sampling. However, when an ultrasound-based approach to such patients is present, a thin distinct end...

  12. Measurement uncertainty of liquid chromatographic analyses visualized by Ishikawa diagrams.

    Science.gov (United States)

    Meyer, Veronika R

    2003-09-01

    Ishikawa, or cause-and-effect diagrams, help to visualize the parameters that influence a chromatographic analysis. Therefore, they facilitate the set up of the uncertainty budget of the analysis, which can then be expressed in mathematical form. If the uncertainty is calculated as the Gaussian sum of all uncertainty parameters, it is necessary to quantitate them all, a task that is usually not practical. The other possible approach is to use the intermediate precision as a base for the uncertainty calculation. In this case, it is at least necessary to consider the uncertainty of the purity of the reference material in addition to the precision data. The Ishikawa diagram is then very simple, and so is the uncertainty calculation. This advantage is given by the loss of information about the parameters that influence the measurement uncertainty.

  13. Measurement Uncertainty of Liquid Chromatographic Analyses Visualized by Ishikawa Diagrams

    OpenAIRE

    Meyer, Veronika R.

    2017-01-01

    Ishikawa, or cause-and-effect diagrams, help to visualize the parameters that influence a chromatographic analysis. Therefore, they facilitate the set up of the uncertainty budget of the analysis, which can then be expressed in mathematical form. If the uncertainty is calculated as the Gaussian sum of all uncertainty parameters, it is necessary to quantitate them all, a task that is usually not practical. The other possible approach is to use the intermediate precision as a base for the uncer...

  14. Human endometrial regenerative cells alleviate carbon tetrachloride-induced acute liver injury in mice

    Directory of Open Access Journals (Sweden)

    Shanzheng Lu

    2016-10-01

    Full Text Available Abstract Background The endometrial regenerative cell (ERC is a novel type of adult mesenchymal stem cell isolated from menstrual blood. Previous studies demonstrated that ERCs possess unique immunoregulatory properties in vitro and in vivo, as well as the ability to differentiate into functional hepatocyte-like cells. For these reasons, the present study was undertaken to explore the effects of ERCs on carbon tetrachloride (CCl4–induced acute liver injury (ALI. Methods An ALI model in C57BL/6 mice was induced by administration of intraperitoneal injection of CCl4. Transplanted ERCs were intravenously injected (1 million/mouse into mice 30 min after ALI induction. Liver function, pathological and immunohistological changes, cell tracking, immune cell populations and cytokine profiles were assessed 24 h after the CCl4 induction. Results ERC treatment effectively decreased the CCl4-induced elevation of serum alanine aminotransferase (ALT and aspartate aminotransferase (AST activities and improved hepatic histopathological abnormalities compared to the untreated ALI group. Immunohistochemical staining showed that over-expression of lymphocyte antigen 6 complex, locus G (Ly6G was markedly inhibited, whereas expression of proliferating cell nuclear antigen (PCNA was increased after ERC treatment. Furthermore, the frequency of CD4+ and CD8+ T cell populations in the spleen was significantly down-regulated, while the percentage of splenic CD4+CD25+FOXP3+ regulatory T cells (Tregs was obviously up-regulated after ERC treatment. Moreover, splenic dendritic cells in ERC-treated mice exhibited dramatically decreased MHC-II expression. Cell tracking studies showed that transplanted PKH26-labeled ERCs engrafted to lung, spleen and injured liver. Compared to untreated controls, mice treated with ERCs had lower levels of IL-1β, IL-6, and TNF-α but higher level of IL-10 in both serum and liver. Conclusions Human ERCs protect the liver from acute injury

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

    Science.gov (United States)

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

    2009-01-01

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

  16. mRNA-binding protein TIA-1 reduces cytokine expression in human endometrial stromal cells and is down-regulated in ectopic endometrium.

    Science.gov (United States)

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

    2014-12-01

    Cytokines and growth factors play important roles in endometrial function and the pathogenesis of endometriosis. mRNAs encoding cytokines and growth factors undergo rapid turnover; primarily mediated by adenosine- and uridine-rich elements (AREs) located in their 3'-untranslated regions. T-cell intracellular antigen (TIA-1), an mRNA-binding protein, binds to AREs in target transcripts, leading to decreased gene expression. The purpose of this article was to determine whether TIA-1 plays a role in the regulation of endometrial cytokine and growth factor expression during the normal menstrual cycle and whether TIA-1 expression is altered in women with endometriosis. Eutopic endometrial tissue obtained from women without endometriosis (n = 30) and eutopic and ectopic endometrial tissues from women with endometriosis (n = 17) were immunostained for TIA-1. Staining intensities were evaluated by histological scores (HSCOREs). The regulation of endometrial TIA-1 expression by immune factors and steroid hormones was studied by treating primary cultured human endometrial stromal cells (HESCs) with vehicle, lipopolysaccharide, TNF-α, IL-6, estradiol, or progesterone, followed by protein blot analyses. HESCs were engineered to over- or underexpress TIA-1 to test whether TIA-1 regulates IL-6 or TNF-α expression in these cells. We found that TIA-1 is expressed in endometrial stromal and glandular cells throughout the menstrual cycle and that this expression is significantly higher in the perimenstrual phase. In women with endometriosis, TIA-1 expression in eutopic and ectopic endometrium was reduced compared with TIA-1 expression in eutopic endometrium of unaffected control women. Lipopolysaccharide and TNF-α increased TIA-1 expression in HESCs in vitro, whereas IL-6 or steroid hormones had no effect. In HESCs, down-regulation of TIA-1 resulted in elevated IL-6 and TNF-α expression, whereas TIA-1 overexpression resulted in decreased IL-6 and TNF-α expression. Endometrial

  17. Expression of two isoforms of CD44 in human endometrium.

    Science.gov (United States)

    Behzad, F; Seif, M W; Campbell, S; Aplin, J D

    1994-10-01

    The distribution of the cell-surface adhesion glycoprotein CD44 in human endometrium was examined by immunofluorescence using six monoclonal antibodies to epitopes common to all forms of the molecule, and by reverse transcription-polymerase chain reaction (RT-PCR). Immunoreactivity was observed throughout the menstrual cycle in stroma, vessels, glandular, and luminal epithelium. Variations in staining intensity were observed, especially in the epithelial compartment. CD44 was also expressed strongly by decidualized stromal cells of first-trimester pregnancy. No systematic variation of immunoreactivity was observed with stages of the normal cycle, but a fraction (25%) of the specimens lacked reactivity in the epithelium. To determine the molecular size of the epithelial isoform, an immunoprecipitation technique was developed using surface-radioiodinated, detergent-extracted glands. This indicated the presence at the cell surface of a single dominant CD44E species with an approximate molecular mass of 130 kDa. RT-PCR was used to investigate the isoforms present in whole endometrial tissue, isolated gland fragments, and Ishikawa endometrial carcinoma cells. Complementary DNA produced from total endometrial mRNA was PCR-amplified across the splice junction between exons 5 and 15. Transcripts corresponding to the hyaluronate receptor CD44H as well as a larger isoform were identified. CD44H was absent, or very scarce, in cDNA from purified gland epithelium. In contrast, Ishikawa cells expressed this form abundantly. The glands and Ishikawa cells also expressed CD44E containing sequences encoded by exons 12, 13, and 14. These data demonstrate the presence of CD44 in human endometrium and decidua, and show that different isoforms of CD44 are associated with tissue compartments in which different functional roles can be anticipated.

  18. Identification of differences in gene expression in primary cell cultures of human endometrial epithelial cells and trophoblast cells following their interaction

    DEFF Research Database (Denmark)

    Høgh, Mette; Islin, Henrik; Møller, Charlotte

    2006-01-01

    The interaction between the cell types was simulated in vitro by growing primary cell cultures of human endometrial epithelial cells and trophoblast cells together (co-culture) and separately (control cultures). Gene expression in the cell cultures was compared using the Differential Display method and confirmed...

  19. Synchrotron- and focal plane array-based Fourier-transform infrared spectroscopy differentiates the basalis and functionalis epithelial endometrial regions and identifies putative stem cell regions of human endometrial glands.

    Science.gov (United States)

    Theophilou, Georgios; Morais, Camilo L M; Halliwell, Diane E; Lima, Kássio M G; Drury, Josephine; Martin-Hirsch, Pierre L; Stringfellow, Helen F; Hapangama, Dharani K; Martin, Francis L

    2018-05-09

    The cyclical process of regeneration of the endometrium suggests that it may contain a cell population that can provide daughter cells with high proliferative potential. These cell lineages are clinically significant as they may represent clonogenic cells that may also be involved in tumourigenesis as well as endometriotic lesion development. To determine whether the putative stem cell location within human uterine tissue can be derived using vibrational spectroscopy techniques, normal endometrial tissue was interrogated by two spectroscopic techniques. Paraffin-embedded uterine tissues containing endometrial glands were sectioned to 10-μm-thick parallel tissue sections and were floated onto BaF 2 slides for synchrotron radiation-based Fourier-transform infrared (SR-FTIR) microspectroscopy and globar focal plane array-based FTIR spectroscopy. Different spectral characteristics were identified depending on the location of the glands examined. The resulting infrared spectra were subjected to multivariate analysis to determine associated biophysical differences along the length of longitudinal and crosscut gland sections. Comparison of the epithelial cellular layer of transverse gland sections revealed alterations indicating the presence of putative transient-amplifying-like cells in the basalis and mitotic cells in the functionalis. SR-FTIR microspectroscopy of the base of the endometrial glands identified the location where putative stem cells may reside at the same time pointing towards ν s PO 2 - in DNA and RNA, nucleic acids and amide I and II vibrations as major discriminating factors. This study supports the view that vibration spectroscopy technologies are a powerful adjunct to our understanding of the stem cell biology of endometrial tissue. Graphical abstract ᅟ.

  20. HMGB1 is negatively correlated with the development of endometrial carcinoma and prevents cancer cell invasion and metastasis by inhibiting the process of epithelial-to-mesenchymal transition

    Directory of Open Access Journals (Sweden)

    Luan XR

    2017-03-01

    Full Text Available Xiaorong Luan,1,2 Chunjing Ma,2 Ping Wang,2 Fenglan Lou1 1Nursing College, Shandong University, 2Qilu Hospital of Shandong University, Jinan, People’s Republic of China Abstract: High-mobility group box protein 1 (HMGB1, a nuclear protein that plays a significant role in DNA architecture and transcription, was correlated with the progression of some types of cancer. However, the role of HMGB1 in endometrial cancer cell invasion and metastasis remains unexplored. HMGB1 expression was initially assessed by immunohistochemistry and reverse transcription-quantitative polymerase chain reaction (RT-qPCR in normal endometrial tissue and endometrial carcinoma tissue. High expressions of HMGB1 protein were detected in normal endometrial tissues; however, in endometrial cancer tissues, the expressions of HMGB1 were found to be very weak. Furthermore, HMGB1 expressions were negatively correlated with advanced stage and lymph node metastasis in endometrial cancer. Then by RT-qPCR, Western blot and immunocytochemistry, HMGB1 was also detected in primary cultured endometrial cells and four kinds of endometrial cancer cell lines (Ishikawa, HEC-1A, HEC-1B and KLE. We found that the expression of HMGB1 was much higher in normal endometrial cells than in endometrial cancer cells, and reduced expression levels of HMGB1 were observed especially in the highly metastatic cell lines. Using lentivirus transfection, HMGB1 small hairpin RNA was constructed, and this infected the lowly invasive endometrial cancer cell lines, Ishikawa and HEC-1B. HMGB1 knockdown significantly enhanced the proliferation, invasion and metastasis of endometrial cancer cells and induced the process of epithelial-to-mesenchymal transition. These results can contribute to the development of a new potential therapeutic target for endometrial cancer. Keywords: HMGB1, endometrial cancer, invasion, metastasis, epithelial-to-mesenchymal transition

  1. SPRY4-mediated ERK1/2 signaling inhibition abolishes 17β-estradiol-induced cell growth in endometrial adenocarcinoma cell.

    Science.gov (United States)

    Li, Mingjiang; Zhang, Hui; Zhao, Xingbo; Yan, Lei; Wang, Chong; Li, Chunyan; Li, Changzhong

    2014-08-01

    Basic fibroblast growth factor (FGF2)-mediated Extracellular signal-regulated kinases1/2 (ERK1/2) signaling is a critical modulator in angiogenesis. SPRY4 has been reported to be a feedback negative regulator of FGFs-induced ERK1/2 signaling. The aim of this study was to explore the role of SPRY4 in endometrial adenocarcinoma cell. The effect of SPRY4 expression on FGF2-mediated ERK1/2 signaling was detected by luciferase assay and Western blot analysis. The growth of Ishikawa cells was detected using colony formation assay and cell number counting experiment. We found that plasmid-driven SPRY4 expression efficiently blocked the activity of FGF2-induced ERK1/2 signaling in Ishikawa cells. SPRY4 expression significantly reduced the proliferation and 17β-estradiol-induced proliferation of Ishikawa cells. SPRY4 may function as a tumor suppressor in endometrial adenocarcinoma.

  2. Effects of ulipristal acetate on human embryo attachment and endometrial cell gene expression in an in vitro co-culture system.

    Science.gov (United States)

    Berger, C; Boggavarapu, N R; Menezes, J; Lalitkumar, P G L; Gemzell-Danielsson, K

    2015-04-01

    Does ulipristal acetate (UPA) used for emergency contraception (EC) interfere with the human embryo implantation process? UPA, at the dosage used for EC, does not affect human embryo implantation process, in vitro. A single pre-ovulatory dose of UPA (30 mg) acts by delaying or inhibiting ovulation and is recommended as first choice among emergency contraceptive pills due to its efficacy. The compound has also been demonstrated to have a dose-dependent effect on the endometrium, which theoretically could impair endometrial receptivity but its direct action on human embryo implantation has not yet been studied. Effect of UPA on embryo implantation process was studied in an in vitro endometrial construct. Human embryos were randomly added to the cultures and cultured for 5 more days with UPA (n = 10) or with vehicle alone (n = 10) to record the attachment of embryos. Endometrial biopsies were obtained from healthy, fertile women on cycle day LH+4 and stromal and epithelial cells were isolated. A three-dimensional in vitro endometrial co-culture system was constructed by mixing stromal cells with collagen covered with a layer of epithelial cells and cultured in progesterone containing medium until confluence. The treatment group received 200 ng/ml of UPA. Healthy, viable human embryos were placed on both control and treatment cultures. Five days later the cultures were tested for the attachment of embryos and the 3D endometrial constructs were analysed for endometrial receptivity markers by real-time PCR. There was no significant difference in the embryo attachment rate between the UPA treated group and the control group as 5 out of 10 human embryos exposed to UPA and 7 out of 10 embryos in the control group attached to the endometrial cell surface (P = 0.650). Out of 17 known receptivity genes studied here, only 2 genes, HBEGF (P = 0.009) and IL6 (P = 0.025) had a significant up-regulation and 4 genes, namely HAND2 (P = 0.003), OPN (P = 0.003), CALCR (P = 0.016) and

  3. Pesquisa da prevalência do papilomavírus humano em amostras de tecido endometrial normal e com carcinoma pela técnica de PCR Search for human papillomavirus in samples of normal endometrial tissue and tissue with carcinoma by the PCR technique

    Directory of Open Access Journals (Sweden)

    Edison Natal Fedrizzi

    2004-05-01

    Full Text Available OBJETIVO: comparar a prevalência da presença do DNA do papilomavírus humano (HPV pela técnica de PCR em amostras de tecido endometrial normal e com carcinoma endometrial de mulheres submetidas a tratamento cirúrgico (histerectomia ou carcinoma endometrial e doença benigna. MÉTODOS: trata-se de um estudo observacional do tipo caso-controle onde foram avaliadas 100 mulheres (50 com endométrio normal e 50 com carcinoma endometrial quanto a presença do DNA do HPV em amostra tecidual conservada em blocos de parafina, pelo método de PCR. Foram excluídos os casos de carcinoma endometrial cujo sítio primário da lesão era duvidoso ou com história prévia ou atual de lesões pré-neoplásicas ou carcinoma do trato genital inferior. Variáveis como idade, tabagismo, trofismo endometrial, diferenciação escamosa e grau de diferenciação tumoral foram também avaliadas. RESULTADOS: o risco relativo estimado da presença do HPV foi o mesmo nas mulheres com e sem carcinoma endometrial. O HPV foi detectado em 8% dos casos de carcinoma e 10% no endométrio normal. Apesar de o HPV ter sido detectado 3,5 vezes mais em mulheres fumantes no grupo sem carcinoma, não houve diferença estatística. A presença do HPV também não esteve correlacionada com a idade das mulheres, trofismo endometrial, diferenciação escamosa e grau de diferenciação tumoral. Os HPV 16 e 18 (5 dos casos com o tipo 16 e 4 com o tipo 18 foram os vírus mais freqüentemente encontrados, tanto no tecido endometrial normal, quanto no carcinomatoso. Nenhum vírus de baixo risco oncogênico foi detectado nas amostras. CONCLUSÃO: o HPV está presente no tecido endometrial de mulheres com carcinoma endometrial na mesma proporção que nas com tecido endometrial normal, não se demonstrando a possível associação deste vírus no desenvolvimento do carcinoma endometrial.OBJECTIVE: to compare the prevalence of DNA of human papillomavirus (HPV, in samples of normal endometrial

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

    Science.gov (United States)

    Liu, Hongyu; Jiang, Yue; Jin, Xiaoyan; Zhu, Lihua; Shen, Xiaoyue; Zhang, Qun; Wang, Bin; Wang, Junxia; Hu, Yali; Yan, Guijun; Sun, Haixiang

    2013-07-15

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

  5. Extended Culture of Encapsulated Human Blastocysts in Alginate Hydrogel Containing Decidualized Endometrial Stromal Cells in the Presence of Melatonin.

    Science.gov (United States)

    Arjmand, Fatemeh; Khanmohammadi, Manijeh; Arasteh, Shaghayegh; Mohammadzadeh, Afsaneh; Kazemnejad, Somaieh; Akhondi, Mohammad-Mehdi

    2016-10-01

    Extended in vitro culture of human embryos beyond blastocyst stage could serve as a tool to explore the molecular and physiological mechanisms underlying embryo development and to identify factors regulating pregnancy outcomes. This study presents the first report on the maintenance of human embryo in vitro by alginate co-encapsulation of human blastocyst and decidualized endometrial stromal cells (EnSCs) under melatonin-fortified culture conditions. The effectiveness of the 3D culture system was studied through monitoring of embryo development in terms of survival time, viability, morphological changes, and production of the two hormones of 17b-oestradiol and human chorionic gonadotropin. The embryo structural integrity was preserved during alginate encapsulation; however, only 23 % of the encapsulated embryos could retain in the hydrogels over time and survived until day 4 post-encapsulation. The culture medium fortification with melatonin significantly elevated the maintenance rate of expanded embryos in alginate beads by 65 % and prolonged survival time of human embryos to day 5. Furthermore, embryo co-culture with EnSCs using melatonin-fortified medium increased the survival time of encapsulated embryos to 44 %. The levels of two measured hormones significantly rose at day 4 in comparison with day 2 post-encapsulation especially in the group co-encapsulated with EnSCs and cultivated in melatonin-fortified culture medium. These data are the first evidence representing in vitro development of human embryos until day 10 post-fertilization. This achievement can facilitate the investigation of the mechanisms regulating human embryo development.

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

    Directory of Open Access Journals (Sweden)

    Dunja Maria Baston-Buest

    2017-01-01

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

  7. Tetraploidization or autophagy: The ultimate fate of senescent human endometrial stem cells under ATM or p53 inhibition.

    Science.gov (United States)

    Borodkina, Aleksandra V; Shatrova, Alla N; Deryabin, Pavel I; Grukova, Anastasiya A; Nikolsky, Nikolay N; Burova, Elena B

    2016-01-01

    Previously we demonstrated that endometrium-derived human mesenchymal stem cells (hMESCs) via activation of the ATM/p53/p21/Rb pathway enter the premature senescence in response to oxidative stress. Down regulation effects of the key components of this signaling pathway, particularly ATM and p53, on a fate of stressed hMESCs have not yet been investigated. In the present study by using the specific inhibitors Ku55933 and Pifithrin-α, we confirmed implication of both ATM and p53 in H(2)O(2)-induced senescence of hMESCs. ATM or p53 down regulation was shown to modulate differently the cellular fate of H(2)O(2)-treated hMESCs. ATM inhibition allowed H(2)O(2)-stimulated hMESCs to escape the permanent cell cycle arrest due to loss of the functional ATM/p53/p21/Rb pathway, and induced bypass of mitosis and re-entry into S phase, resulting in tetraploid cells. On the contrary, suppression of the p53 transcriptional activity caused a pronounced cell death of H(2)O(2)-treated hMESCs via autophagy induction. The obtained data clearly demonstrate that down regulation of ATM or p53 shifts senescence of human endometrial stem cells toward tetraploidization or autophagy.

  8. Characterization of a novel telomerase-immortalized human endometrial stromal cell line, St-T1b

    Directory of Open Access Journals (Sweden)

    Brosens Jan J

    2009-07-01

    Full Text Available Abstract Background Coordinated differentiation of the endometrial compartments in the second half of the menstrual cycle is a prerequisite for the establishment of pregnancy. Endometrial stromal cells (ESC decidualize under the influence of ovarian progesterone to accommodate implantation of the blastocyst and support establishment of the placenta. Studies into the mechanisms of decidualization are often hampered by the lack of primary ESC. Here we describe a novel immortalized human ESC line. Methods Primary ESC were immortalized by the transduction of telomerase. The resultant cell line, termed St-T1b, was characterized for its morphological and biochemical properties by immunocytochemistry, RT-PCR and immunoblotting. Its progestational response was tested using progesterone and medroxyprogesterone acetate with and without 8-Br-cAMP, an established inducer of decidualization in vitro. Results St-T1b were positive for the fibroblast markers vimentin and CD90 and negative for the epithelial marker cytokeratin-7. They acquired a decidual phenotype indistinguishable from primary ESC in response to cAMP stimulation. The decidual response was characterized by transcriptional activation of marker genes, such as PRL, IGFBP1, and FOXO1, and enhanced protein levels of the tumor suppressor p53 and the metastasis suppressor KAI1 (CD82. Progestins alone had no effect on St-T1b cells, but medroxyprogesterone acetate greatly enhanced the cAMP-stimulated expression of IGFBP-1 after 3 and 7 days. Progesterone, albeit more weakly, also augmented the cAMP-induced IGFBP-1 production but only after 7 days of treatment. The cell line remained stable in continuous culture for more than 150 passages. Conclusion St-T1b express the appropriate phenotypic ESC markers and their decidual response closely mimics that of primary cultures. Decidualization is efficiently induced by cAMP analog and enhanced by medroxyprogesterone acetate, and, to a lesser extent, by natural

  9. Upregulation of estrogen receptor expression in the uterus of ovariectomized B6C3F1 mice and Ishikawa cells treated with bromoethane

    International Nuclear Information System (INIS)

    Aoyama, Hiroaki; Couse, John F.; Hewitt, Sylvia C.; Haseman, Joseph K.; He, Hong; Zheng, Xiaolin; Majstoravich, Sonja; Korach, Kenneth S.; Dixon, D.

    2005-01-01

    In a 2-year NTP bioassay, Bromoethane (BE) was found to induce endometrial neoplasms in the uterus of B6C3F1 mice [; ]. In women, hormonal influences, such as 'unopposed' estrogenic stimulus, have been implicated as important etiologic factors in uterine cancer. BE, however, does not affect the serum concentrations of sex hormones in female B6C3F1 mice [] and the mechanism of BE-induced uterine carcinogenesis still remains unclear. In the present study, we examined the estrogenic effects of BE on the uterus of ovariectomized B6C3F1 mice and on Ishikawa cells. Groups of 6 mice were given daily s.c. injections of 0, 100, 500 or 1000 mg BE/kg for 3 consecutive days. Mice treated with 17β-estradiol served as positive controls. Mice were necropsied 24 h after the final injection, and uteri were weighed and examined histologically and immunohistochemically along with the vagina. Changes observed in the estrogen-treated mice included increased uterine weights, edema and inflammation of the endometrium, increased epithelial layers of the uterine and vaginal lumens and keratinization of the vaginal epithelium. In the BE-treated mice, no such changes occurred; however, immunohistochemical staining of the uterus revealed a significant increase in immunoexpression of the estrogen receptor alpha (ERα) in the two higher dose groups. Analysis of mRNA also showed slightly increased uterine ERα expression in these groups. Upregulated expression of ERα was confirmed in BE-treated Ishikawa cells, in which Western blotting analyses identified an intense signal at approximately 66 kDa, which is consistent with ERα. These data suggest that upregulated expression of ERα may be important in the induction of endometrial neoplasms in BE-treated mice

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

    Directory of Open Access Journals (Sweden)

    Ozlem Guzeloglu Kayisli

    Full Text Available 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

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

    Science.gov (United States)

    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

  12. Intrauterine human chorionic gonadotropin infusion in oocyte donors promotes endometrial synchrony and induction of early decidual markers for stromal survival: a randomized clinical trial.

    Science.gov (United States)

    Strug, Michael R; Su, Renwei; Young, James E; Dodds, William G; Shavell, Valerie I; Díaz-Gimeno, Patricia; Ruíz-Alonso, Maria; Simón, Carlos; Lessey, Bruce A; Leach, Richard E; Fazleabas, Asgerally T

    2016-07-01

    Does a single intrauterine infusion of human chorionic gonadotropin (hCG) at the time corresponding to a Day 3 embryo transfer in oocyte donors induce favorable molecular changes in the endometrium for embryo implantation? Intrauterine hCG was associated with endometrial synchronization between endometrial glands and stroma following ovarian stimulation and the induction of early decidual markers associated with stromal cell survival. The clinical potential for increasing IVF success rates using an intrauterine hCG infusion prior to embryo transfer remains unclear based on previously reported positive and non-significant findings. However, infusion of CG in the non-human primate increases the expression of pro-survival early decidual markers important for endometrial receptivity, including α-smooth muscle actin (α-SMA) and NOTCH1. Oocyte donors (n=15) were randomly assigned to receive an intrauterine infusion of 500 IU hCG (n=7) or embryo culture media vehicle (n=8) 3 days following oocyte retrieval during their donor stimulation cycle. Endometrial biopsies were performed 2 days later, followed by either RNA isolation or tissue fixation in formalin and paraffin embedding. Reverse transcription of total RNA from endometrial biopsies generated cDNA, which was used for analysis in the endometrial receptivity array (ERA; n = 5/group) or quantitative RT-PCR to determine relative expression of ESR1, PGR, C3 and NOTCH1. Tissue sections were stained with hematoxylin and eosin followed by blinded staging analysis for dating of endometrial glands and stroma. Immunostaining for ESR1, PGR, α-SMA, C3 and NOTCH1 was performed to determine their tissue localization. Intrauterine hCG infusion was associated with endometrial synchrony and reprograming of stromal development following ovarian stimulation. ESR1 and PGR were significantly elevated in the endometrium of hCG-treated patients, consistent with earlier staging. The ERA did not predict an overall positive impact of

  13. Investigation of Shrinkage Defect in Castings by Quantitative Ishikawa Diagram

    Directory of Open Access Journals (Sweden)

    Chokkalingam B.

    2017-03-01

    Full Text Available Metal casting process involves processes such as pattern making, moulding and melting etc. Casting defects occur due to combination of various processes even though efforts are taken to control them. The first step in the defect analysis is to identify the major casting defect among the many casting defects. Then the analysis is to be made to find the root cause of the particular defect. Moreover, it is especially difficult to identify the root causes of the defect. Therefore, a systematic method is required to identify the root cause of the defect among possible causes, consequently specific remedial measures have to be implemented to control them. This paper presents a systematic procedure to identify the root cause of shrinkage defect in an automobile body casting (SG 500/7 and control it by the application of Pareto chart and Ishikawa diagram. with quantitative Weightage. It was found that the root causes were larger volume section in the cope, insufficient feeding of riser and insufficient poured metal in the riser. The necessary remedial measures were taken and castings were reproduced. The shrinkage defect in the castings was completely eliminated.

  14. Ubiquitin-proteasomal degradation of COX-2 in TGF-β stimulated human endometrial cells is mediated through endoplasmic reticulum mannosidase I.

    Science.gov (United States)

    Singh, Mohan; Chaudhry, Parvesh; Parent, Sophie; Asselin, Eric

    2012-01-01

    Cyclooxygenase (COX)-2 is a key regulatory enzyme in the production of prostaglandins (PG) during various physiological processes. Mechanisms of COX-2 regulation in human endometrial stromal cells (human endometrial stromal cells) are not fully understood. In this study, we investigate the role of TGF-β in the regulation of COX-2 in human uterine stromal cells. Each TGF-β isoform decreases COX-2 protein level in human uterine stromal cells in Smad2/3-dependent manner. The decrease in COX-2 is accompanied by a decrease in PG synthesis. Knockdown of Smad4 using specific small interfering RNA prevents the decrease in COX-2 protein, confirming that Smad pathway is implicated in the regulation of COX-2 expression in human endometrial stromal cells. Pretreatment with 26S proteasome inhibitor, MG132, significantly restores COX-2 protein and PG synthesis, indicating that COX-2 undergoes proteasomal degradation in the presence of TGF-β. In addition, each TGF-β isoform up-regulates endoplasmic reticulum (ER)-mannosidase I (ERManI) implying that COX-2 degradation is mediated through ER-associated degradation pathway in these cells. Furthermore, inhibition of ERManI activity using the mannosidase inhibitor (kifunensine), or small interfering RNA-mediated knockdown of ERManI, prevents TGF-β-induced COX-2 degradation. Taken together, these studies suggest that TGF-β promotes COX-2 degradation in a Smad-dependent manner by up-regulating the expression of ERManI and thereby enhancing ER-associated degradation and proteasomal degradation pathways.

  15. Elevated expression of CD147 in patients with endometriosis and its role in regulating apoptosis and migration of human endometrial cells.

    Science.gov (United States)

    Jin, Aihong; Chen, Hao; Wang, Chaoqun; Tsang, Lai Ling; Jiang, Xiaohua; Cai, Zhiming; Chan, Hsiao Chang; Zhou, Xiaping

    2014-06-01

    To examine the expression of CD147 in 60 human endometriosis lesions and how CD147 regulates migration and apoptosis in human uterine epithelial (HESs) cells. Experimental clinical study and laboratory-based investigation. Hospital and academic research center. Sixty women with chocolate cysts and 16 control women without endometriosis. Human uterine epithelial cells were treated with anti-CD147 antibody. Real-time polymerase chain reaction for detecting CD147 expression in 60 human endometriosis lesions; migration assay and CellTiter 96 AQueous One Solution Cell Proliferation Assay (MTS) assay for cell functional investigation; Western blot for detecting protein levels; gelatin zymography for evaluating the activity of matrix metalloproteinase-2 (MMP-2) in cultured cells. Expression of CD147 was significantly higher in ectopic endometrial tissues from patients with endometriosis than in normal endometrial tissues. Interference with CD147 function led to decreased migration and cell viability in HESs cells. Surprisingly, MMP-2 expression and activity were not changed after treating HESs cells with anti-CD147 antibody. Further examination revealed that immunodepletion of CD147 induced apoptosis in HESs cells, leading to the activation of caspase 3 and poly(ADP-ribose) polymerase. The results of the present study suggest that abnormally high expression of CD147 in ovarian endometriosis lesions with enhanced cell survival (reduced apoptosis) and migration, in an MMP-2-independent manner, may underlie the progression of endometriosis in humans. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  16. Trappin-2/elafin modulate innate immune responses of human endometrial epithelial cells to PolyI:C.

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    Anna G Drannik

    Full Text Available BACKGROUND: Upon viral recognition, innate and adaptive antiviral immune responses are initiated by genital epithelial cells (ECs to eradicate or contain viral infection. Such responses, however, are often accompanied by inflammation that contributes to acquisition and progression of sexually transmitted infections (STIs. Hence, interventions/factors enhancing antiviral protection while reducing inflammation may prove beneficial in controlling the spread of STIs. Serine antiprotease trappin-2 (Tr and its cleaved form, elafin (E, are alarm antimicrobials secreted by multiple cells, including genital epithelia. METHODOLOGY AND PRINCIPAL FINDINGS: We investigated whether and how each Tr and E (Tr/E contribute to antiviral defenses against a synthetic mimic of viral dsRNA, polyinosine-polycytidylic acid (polyI:C and vesicular stomatitis virus. We show that delivery of a replication-deficient adenovector expressing Tr gene (Ad/Tr to human endometrial epithelial cells, HEC-1A, resulted in secretion of functional Tr, whereas both Tr/E were detected in response to polyI:C. Moreover, Tr/E were found to significantly reduce viral replication by either acting directly on virus or through enhancing polyI:C-driven antiviral protection. The latter was associated with reduced levels of pro-inflammatory factors IL-8, IL-6, TNFα, lowered expression of RIG-I, MDA5 and attenuated NF-κB activation. Interestingly, enhanced polyI:C-driven antiviral protection of HEC-Ad/Tr cells was partially mediated through IRF3 activation, but not associated with higher induction of IFNβ, suggesting multiple antiviral mechanisms of Tr/E and the involvement of alternative factors or pathways. CONCLUSIONS AND SIGNIFICANCE: This is the first evidence of both Tr/E altering viral binding/entry, innate recognition and mounting of antiviral and inflammatory responses in genital ECs that could have significant implications for homeostasis of the female genital tract.

  17. Alterations of DNA content in human endometrial stromal cells transfected with a temperature-sensitive SV40: tetraploidization and physiological consequences.

    Science.gov (United States)

    Rinehart, C A; Mayben, J P; Butler, T D; Haskill, J S; Kaufman, D G

    1992-01-01

    The normal genomic stability of human cells is reversed during neoplastic transformation. The SV40 large T antigen alters the DNA content in human endometrial stromal cells in a manner that relates to neoplastic progression. Human endometrial stromal cells were transfected with a plasmid containing the A209 temperature-sensitive mutant of SV40 (tsSV40), which is also defective in the viral origin of replication. Ninety-seven clonal transfectants from seven different primary cell strains were isolated. Initial analysis revealed that 20% of the clonal populations (19/97) had an apparent diploid DNA content, 35% (34/97) had an apparent tetraploid DNA content, and the remainder were mixed populations of diploid and tetraploid cells. No aneuploid populations were observed. Diploid tsSV40 transformed cells always give rise to a population of cells with a tetraploid DNA content when continuously cultured at the permissive temperature. The doubling of DNA content can be vastly accelerated by the sudden reintroduction of large T antigen activity following a shift from non-permissive to permissive temperature. Tetraploid tsSV40 transfected cells have a lower capacity for anchorage-independent growth and earlier entry into 'crisis' than diploid cells. These results indicate that during the pre-crisis, extended lifespan phase of growth, the SV40 large T antigen causes a doubling of DNA content. This apparent doubling of DNA content does not confer growth advantage during the extended lifespan that precedes 'crisis'.

  18. Bisphenol A Alters β-hCG and MIF Release by Human Placenta: An In Vitro Study to Understand the Role of Endometrial Cells

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    C. Mannelli

    2014-01-01

    Full Text Available A proper fetomaternal immune-endocrine cross-talk in pregnancy is fundamental for reproductive success. This might be unbalanced by exposure to environmental chemicals, such as bisphenol A (BPA. As fetoplacental contamination with BPA originates from the maternal compartment, this study investigated the role of the endometrium in BPA effects on the placenta. To this end, in vitro decidualized stromal cells were exposed to BPA 1 nM, and their conditioned medium (diluted 1 : 2 was used on chorionic villous explants from human placenta. Parallel cultures of placental explants were directly exposed to 0.5 nM BPA while, control cultures were exposed to the vehicle (EtOH 0.1%. After 24–48 h, culture medium from BPA-treated and control cultures was assayed for concentration of hormone human Chorionic Gonadotropin (β-hCG and cytokine Macrophage Migration Inhibitory Factor (MIF. The results showed that direct exposure to BPA stimulated the release of both MIF and β-hCG. These effects were abolished/diminished in placental cultures exposed to endometrial cell-conditioned medium. GM-MS analysis revealed that endometrial cells retain BPA, thus reducing the availability of this chemical for the placenta. The data obtained highlight the importance of in vitro models including the maternal component in reproducing the effects of environmental chemicals on human fetus/placenta.

  19. Antitumor Effects and Biological Mechanism of Action of the Aqueous Extract of the Camptotheca acuminata Fruit in Human Endometrial Carcinoma Cells

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    Chi-Shian Lin

    2014-01-01

    Full Text Available The aqueous extracts of the leaves and fruit of Camptotheca acuminata have long been used in traditional Chinese medicine (TCM for treating cancer patients. The chemotherapeutic drug, camptothecin (CPT, and related analogs were first isolated from C. acuminata in the 1970s. Although the antitumor effects of CPT have been characterized in recent years, the antitumor effects of aqueous extracts of C. acuminata have not been clarified. The aims of our current study were to determine the tumor-suppression efficiency of an aqueous extract of the fruit of C. acuminata (AE-CA in the human endometrial carcinoma cell lines, HEC-1A, HEC-1B, and KLE, and compare its antitumor effects with those of CPT. Cell viability assays indicated that a dosage of AE-CA containing 0.28 mg/mL of CPT demonstrated enhanced cytotoxicity, compared with CPT treatment. The effects of AE-CA on the induction of cell cycle arrest, the accumulation of cyclin-A2 and -B1, and the activation of caspase-3 and caspase-7 were similar to those of CPT. Furthermore, AE-CA exhibited a synergistic effect on the cytotoxicity of cisplatin in HEC-1A and HEC-1B cells. These results indicated that AE-CA is a potent antitumor agent and can be combined with cisplatin for the treatment of human endometrial cancer.

  20. [Regulation of microRNA-199a on adhesion, migration and invasion ability of human endometrial stromal cells].

    Science.gov (United States)

    Dai, Lan; Gu, Li-ying; Zhu, Jie; Shi, Jun; Wang, Yao; Ji, Fang; Di, Wen

    2011-11-01

    To study the regulation of microRNA 199a (miR-199a) on adhesion, migration and invasion ability of human eutopic endometrial stromal cells (ESC) from patients with endometriosis. ESC were transfected with miR-199a mimics or negative control (NC) RNA by lipofectamine 2000. The adhesion, migration and invasion ability of ESC were detected by cell adhesion assay, scratch assay, cell migration assay and matrigel invasion assay, respectively. Luciferase reporter assay was used to evaluate whether IKKβ was the target gene of miR-199a. The expression of ikappa B kinase beta (IKKβ), inhibitory kappa B alpha (IκB-α), phospho-IκB-α(p-IκB-α) and nuclear factor-kappa B (NF-κB) protein were measured by western blot. (1) Adhesion potential: the adhesion inhibitory rates were (14 ± 4)% in miR-199a group and 0 in control group, which showed significant difference (P scratch assay, ESC transfected with miR-199a exhibited a lower scratch closure rate than that of controls. In migration and invasion assays, the migration and invasion ability of miR-199a group were significantly decreased compared with those of NC group [130 ± 31 vs. 247 ± 36 (P < 0.01); 63 ± 15 vs. 133 ± 17 (P < 0.01), respectively]. (3) The luciferase activity of miR-199a group was significantly lowered than that of control group [0.160 ± 0.006 vs. 0.383 ± 0.083 (P < 0.01)]. The protein levels of IKKβ, p-IκB-α, IκB-α and NF-κB of 0.350 ± 0.195, 0.443 ± 0.076, 1.970 ± 0.486 and 0.454 ± 0.147 in miR-199a group were significantly different compared with the NC group in which the protein levels were set at 1.000 (P < 0.01). miR-199a can inhibit the adhesion, migration and invasion of the ESC. IKKβ is the target gene of miR-199a in ESC. One of the mechanisms of the inhibition effect is probably that miR-199a inhibits the activation of NF-κB signaling pathway by targeting IKKβ gene.

  1. The Anticancer Effects of Radachlorin-mediated Photodynamic Therapy in the Human Endometrial Adenocarcinoma Cell Line HEC-1-A.

    Science.gov (United States)

    Kim, Su-Mi; Rhee, Yun-Hee; Kim, Jong-Soo

    2017-11-01

    We investigated the effect of photodynamic therapy (PDT) using radachlorin on invasion, vascular formation and apoptosis by targeting epidermal growth factor receptor (EGFR)/vascular endothelial growth factor receptor 2 (VEGFR2) signaling pathways in the HEC-1-A endometrial adenocarcinoma cell line. To investigate the apoptotic pathway, we performed the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay, and western blot analysis. We also evaluated the effects of PDT on tubular capillary formation in and invasion by HEC-1-A cells with a tube formation assay, invasion assay, prostaglandin E2 (PGE2) assay, and western blot analysis. PDT had anticancer effects on HEC-1-A through activation of the intrinsic pathway of apoptosis via caspase-9 and poly-(ADP-ribose) polymerase (PARP). PDT also inhibited tubular capillary formation in and invasion by HEC-1-A under VEGF pretreatment, that resulted from down-regulation of VEGFR2, EGFR, Ras homolog gene family/ member A (RhoA) and PGE2. These results are indicative of the specificity of radachlorin-mediated PDT to VEGF. The major advantage of radachlorin-mediated PDT is its selectivity for cancer tissue while maintaining adjacent normal endometrial tissue. Therefore, radachlorin-mediated PDT might offer high anticancer efficacy for endometrial adenocarcinoma and an especially useful modality for preserving fertility. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  2. STUDY TO DETERMINE A NEW MODEL OF THE ISHIKAWA DIAGRAM FOR QUALITY IMPROVEMENT

    Directory of Open Access Journals (Sweden)

    Liliana LUCA

    2017-05-01

    Full Text Available The paper presents the results of a study concerning the use of the Ishikawa diagram in analyzing the causes that determine the improvement of the quality of education in a university. All the possible, main and secondary causes that could generate the studied problem were identified. We determined six possible main causes: Man-professor, Man- student, Methods, Materials, Environment for Teaching and Learning, Quality Management. All main causes and secondary causes described a new Ishikawa diagram, a new model with 4 M + 1E + 1Q.

  3. Application of the Pareto chart and Ishikawa diagram for the identification of major defects in metal composite castings

    Directory of Open Access Journals (Sweden)

    K. Gawdzińska

    2011-04-01

    Full Text Available This author discusses the use of selected quality management tools, i.e. the Pareto chart and Ishikawa fishbone diagram, for the descriptionof composite casting defects. The Pareto chart allows to determine defect priority related with metallic composite castings, while theIshikawa diagram indicates the causes of defect formation and enables calculating defect weights.

  4. Application of the Pareto chart and Ishikawa diagram for the identification of major defects in metal composite castings

    OpenAIRE

    K. Gawdzińska

    2011-01-01

    This author discusses the use of selected quality management tools, i.e. the Pareto chart and Ishikawa fishbone diagram, for the descriptionof composite casting defects. The Pareto chart allows to determine defect priority related with metallic composite castings, while theIshikawa diagram indicates the causes of defect formation and enables calculating defect weights.

  5. Interferon-gamma and tumor necrosis factor-alpha sensitize primarily resistant human endometrial stromal cells to Fas-mediated apoptosis

    DEFF Research Database (Denmark)

    Fluhr, Herbert; Krenzer, Stefanie; Stein, Gerburg M

    2007-01-01

    The subtle interaction between the implanting embryo and the maternal endometrium plays a pivotal role during the process of implantation. Human endometrial stromal cells (ESCs) express Fas and the implanting trophoblast cells secrete Fas ligand (FASLG, FasL), suggesting a possible role for Fas......-mediated signaling during early implantation. Here we show that ESCs are primarily resistant to Fas-mediated apoptosis independently of their state of hormonal differentiation. Pre-treatment of ESCs with interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha sensitizes them to become apoptotic upon stimulation...... of Fas by an agonistic anti-Fas antibody. Incubation of ESCs with the early embryonic signal human chorionic gonadotropin (hCG, CGB) does not influence their reaction to Fas stimulation. The sensitizing effect of IFN-gamma and TNF-alpha was accompanied by a significant upregulation of Fas and FLICE...

  6. Cannabinoid-induced cell death in endometrial cancer cells: involvement of TRPV1 receptors in apoptosis.

    Science.gov (United States)

    Fonseca, B M; Correia-da-Silva, G; Teixeira, N A

    2018-05-01

    Among a variety of phytocannabinoids, Δ 9 -tetrahydrocannabinol (THC) and cannabidiol (CBD) are the most promising therapeutic compounds. Besides the well-known palliative effects in cancer patients, cannabinoids have been shown to inhibit in vitro growth of tumor cells. Likewise, the major endocannabinoids (eCBs), anandamide (AEA) and 2-arachidonoylglycerol (2-AG), induce tumor cell death. The purpose of the present study was to characterize cannabinoid elements and evaluate the effect of cannabinoids in endometrial cancer cell viability. The presence of cannabinoid receptors, transient receptor potential vanilloid 1 (TRPV1), and endocannabinoid-metabolizing enzymes were determined by qRT-PCR and Western blot. We also examined the effects and the underlying mechanisms induced by eCBs and phytocannabinoids in endometrial cancer cell viability. Besides TRPV1, both EC cell lines express all the constituents of the endocannabinoid system. We observed that at concentrations higher than 5 μM, eCBs and CBD induced a significant reduction in cell viability in both Ishikawa and Hec50co cells, whereas THC did not cause any effect. In Ishikawa cells, contrary to Hec50co, treatment with AEA and CBD resulted in an increase in the levels of activated caspase -3/-7, in cleaved PARP, and in reactive oxygen species generation, confirming that the reduction in cell viability observed in the MTT assay was caused by the activation of the apoptotic pathway. Finally, these effects were dependent on TRPV1 activation and intracellular calcium levels. These data indicate that cannabinoids modulate endometrial cancer cell death. Selective targeting of TPRV1 by AEA, CBD, or other stable analogues may be an attractive research area for the treatment of estrogen-dependent endometrial carcinoma. Our data further support the evaluation of CBD and CBD-rich extracts for the potential treatment of endometrial cancer, particularly, that has become non-responsive to common therapies.

  7. The impact of 27-hydroxycholesterol on endometrial cancer proliferation.

    Science.gov (United States)

    Gibson, Douglas A; Collins, Frances; Cousins, Fiona L; Esnal Zufiaurre, Arantza; Saunders, Philippa T K

    2018-04-01

    Endometrial cancer (EC) is the most common gynaecological malignancy. Obesity is a major risk factor for EC and is associated with elevated cholesterol. 27-hydroxycholesterol (27HC) is a cholesterol metabolite that functions as an endogenous agonist for Liver X receptor (LXR) and a selective oestrogen receptor modulator (SERM). Exposure to oestrogenic ligands increases risk of developing EC; however, the impact of 27HC on EC is unknown. Samples of stage 1 EC ( n  = 126) were collected from postmenopausal women undergoing hysterectomy. Expression of LXRs ( NR1H3 , LXRα; NR1H2 , LXRβ) and enzymes required for the synthesis ( CYP27A1 ) or breakdown ( CYP7B1 ) of 27HC were detected in all grades of EC. Cell lines originating from well-, moderate- and poorly-differentiated ECs (Ishikawa, RL95, MFE 280 respectively) were used to assess the impact of 27HC or the LXR agonist GW3965 on proliferation or expression of a luciferase reporter gene under the control of LXR- or ER-dependent promoters (LXRE, ERE). Incubation with 27HC or GW3965 increased transcription via LXRE in Ishikawa, RL95 and MFE 280 cells ( P  MFE 280 cells, 27HC did not alter proliferation but selective targeting of LXR with GW3965 significantly reduced cell proliferation ( P  < 0.0001). These novel results suggest that 27HC can contribute to risk of EC by promoting proliferation of endometrial cancer epithelial cells and highlight LXR as a potential therapeutic target in the treatment of advanced disease. © 2018 The authors.

  8. Expression pattern of matrix metalloproteinases in human gynecological cancer cell lines

    International Nuclear Information System (INIS)

    Schröpfer, Andrea; Kammerer, Ulrike; Kapp, Michaela; Dietl, Johannes; Feix, Sonja; Anacker, Jelena

    2010-01-01

    Matrix metalloproteinases (MMPs) are involved in the degradation of protein components of the extracellular matrix and thus play an important role in tumor invasion and metastasis. Their expression is related to the progression of gynecological cancers (e.g. endometrial, cervical or ovarian carcinoma). In this study we investigated the expression pattern of the 23 MMPs, currently known in humans, in different gynecological cancer cell lines. In total, cell lines from three endometrium carcinomas (Ishikawa, HEC-1-A, AN3 CA), three cervical carcinomas (HeLa, Caski, SiHa), three chorioncarcinomas (JEG, JAR, BeWo), two ovarian cancers (BG-1, OAW-42) and one teratocarcinoma (PA-1) were examined. The expression of MMPs was analyzed by RT-PCR, Western blot and gelatin zymography. We demonstrated that the cell lines examined can constitutively express a wide variety of MMPs on mRNA and protein level. While MMP-2, -11, -14 and -24 were widely expressed, no expression was seen for MMP-12, -16, -20, -25, -26, -27 in any of the cell lines. A broad range of 16 MMPs could be found in the PA1 cells and thus this cell line could be used as a positive control for general MMP experiments. While the three cervical cancer cell lines expressed 10-14 different MMPs, the median expression in endometrial and choriocarcinoma cells was 7 different enzymes. The two investigated ovarian cancer cell lines showed a distinctive difference in the number of expressed MMPs (2 vs. 10). Ishikawa, Caski, OAW-42 and BeWo cell lines could be the best choice for all future experiments on MMP regulation and their role in endometrial, cervical, ovarian or choriocarcinoma development, whereas the teratocarcinoma cell line PA1 could be used as a positive control for general MMP experiments

  9. 7,12-Dimethylbenzanthracene induces apoptosis in RL95-2 human endometrial cancer cells: Ligand-selective activation of cytochrome P450 1B1

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ji Young [Department of Anatomy and Cell Biology, College of Medicine, Dong-A University, Busan 602-714 (Korea, Republic of); Medical Research Science Center, Dong-A University, Busan 602-714 (Korea, Republic of); Lee, Seung Gee [Department of Anatomy and Cell Biology, College of Medicine, Dong-A University, Busan 602-714 (Korea, Republic of); Mitochondria Hub Regulation Center, Dong-A University, Busan 602-714 (Korea, Republic of); Chung, Jin-Yong [Department of Anatomy and Cell Biology, College of Medicine, Dong-A University, Busan 602-714 (Korea, Republic of); Medical Research Science Center, Dong-A University, Busan 602-714 (Korea, Republic of); Kim, Yoon-Jae [Department of Anatomy and Cell Biology, College of Medicine, Dong-A University, Busan 602-714 (Korea, Republic of); Mitochondria Hub Regulation Center, Dong-A University, Busan 602-714 (Korea, Republic of); Park, Ji-Eun [Department of Anatomy and Cell Biology, College of Medicine, Dong-A University, Busan 602-714 (Korea, Republic of); Medical Research Science Center, Dong-A University, Busan 602-714 (Korea, Republic of); Oh, Seunghoon [Department of Physiology, College of Medicine, Dankook University, Cheonan 330-714 (Korea, Republic of); Lee, Se Yong [Department of Obstetrics and Gynecology, Busan Medical Center, Busan 611-072 (Korea, Republic of); Choi, Hong Jo [Department of General Surgery, College of Medicine, Dong-A University, Busan 602-714 (Korea, Republic of); Yoo, Young Hyun, E-mail: yhyoo@dau.ac.kr [Department of Anatomy and Cell Biology, College of Medicine, Dong-A University, Busan 602-714 (Korea, Republic of); Mitochondria Hub Regulation Center, Dong-A University, Busan 602-714 (Korea, Republic of); Medical Research Science Center, Dong-A University, Busan 602-714 (Korea, Republic of); and others

    2012-04-15

    7,12-Dimethylbenzanthracene (DMBA), a polycyclic aromatic hydrocarbon, exhibits mutagenic, carcinogenic, immunosuppressive, and apoptogenic properties in various cell types. To achieve these functions effectively, DMBA is modified to its active form by cytochrome P450 1 (CYP1). Exposure to DMBA causes cytotoxicity-mediated apoptosis in bone marrow B cells and ovarian cells. Although uterine endometrium constitutively expresses CYP1A1 and CYP1B1, their apoptotic role after exposure to DMBA remains to be elucidated. Therefore, we chose RL95-2 endometrial cancer cells as a model system for studying DMBA-induced cytotoxicity and cell death and hypothesized that exposure to DMBA causes apoptosis in this cell type following CYP1A1 and/or CYP1B1 activation. We showed that DMBA-induced apoptosis in RL95-2 cells is associated with activation of caspases. In addition, mitochondrial changes, including decrease in mitochondrial potential and release of mitochondrial cytochrome c into the cytosol, support the hypothesis that a mitochondrial pathway is involved in DMBA-induced apoptosis. Exposure to DMBA upregulated the expression of AhR, Arnt, CYP1A1, and CYP1B1 significantly; this may be necessary for the conversion of DMBA to DMBA-3,4-diol-1,2-epoxide (DMBA-DE). Although both CYP1A1 and CYP1B1 were significantly upregulated by DMBA, only CYP1B1 exhibited activity. Moreover, knockdown of CYP1B1 abolished DMBA-induced apoptosis in RL95-2 cells. Our data show that RL95-2 cells are susceptible to apoptosis by exposure to DMBA and that CYP1B1 plays a pivotal role in DMBA-induced apoptosis in this system. -- Highlights: ► Cytotoxicity-mediated apoptogenic action of DMBA in human endometrial cancer cells. ► Mitochondrial pathway in DMBA-induced apoptosis of RL95-2 endometrial cancer cells. ► Requirement of ligand-selective activation of CYP1B1 in DMBA-induced apoptosis.

  10. Impact of ER520, a candidate of selective estrogen receptor modulators, on in vitro cell growth, migration, invasion, angiogenesis and in vivo tumor xenograft of human breast cancer cells.

    Science.gov (United States)

    Wang, Lijun; Wang, Ying; Du, Huaqing; Jiang, Yao; Tang, Zhichao; Liu, Hongyi; Xiang, Hua; Xiao, Hong

    2015-12-01

    ER520, a derivative of indenoisoquinoline, is a patented compound. This study was designed to screen its biological properties and to evaluate its antineoplastic and antiangiogenic effect. Western blot was employed to monitor the ERα and ERβ protein expression in human breast cancer MCF-7 cells and endometrial carcinoma Ishikawa cells. MTT assay was employed to determine cell proliferation. Cell adhesion, scratch and Transwell assay were utilized to estimate the ability of cellular adhesion, migration and invasion. ELISA kit was applied to detect the VEGF products in culture medium. In addition, the inhibitory effect of ER520 on the vessel-like construction of HUVEC cells and the angiogenesis of chicken embryos was investigated. The efficiency of ER520 on tumor growth in nude mice was also assessed. ER520 inhibited the expression of ERα in MCF-7 and Ishikawa cells, while it increased ERβ protein level. ER520 also suppressed the proliferation of MCF-7 and Ishikawa cells. Due to its remarkably negative role in cell adhesion, migration and invasion, ER520 showed a potential ability of inhibiting tumor metastasis. Meanwhile, ER520 reduced the VEGF secretion of MCF-7 and Ishikawa cells, prevented the formation of VEGF-stimulated tubular structure and the cell migration of HUVEC cells, and inhibited the angiogenesis of chicken chorioallantoic membrane. Animal experiment also demonstrated that ER520 could frustrate the in vivo tumor growth and the inhibitory ratio was 48.5 % compared with control group. Our findings indicate that ER520 possesses the competence to be a candidate against breast cancer and angiogenesis.

  11. STUDY TO DETERMINE A NEW MODEL OF THE ISHIKAWA DIAGRAM FOR QUALITY IMPROVEMENT

    OpenAIRE

    Liliana LUCA; Minodora PASARE; Alin STANCIOIU

    2017-01-01

    The paper presents the results of a study concerning the use of the Ishikawa diagram in analyzing the causes that determine the improvement of the quality of education in a university. All the possible, main and secondary causes that could generate the studied problem were identified. We determined six possible main causes: Man-professor, Man- student, Methods, Materials, Environment for Teaching and Learning, Quality Management. All main causes and secondary causes described a ne...

  12. Using an Ishikawa diagram as a tool to assist memory and retrieval of relevant medical cases from the medical literature

    OpenAIRE

    Wong, Kam Cheong

    2011-01-01

    Abstract Studying medical cases is an effective way to enhance clinical reasoning skills and reinforce clinical knowledge. An Ishikawa diagram, also known as a cause-and-effect diagram or fishbone diagram, is often used in quality management in manufacturing industries. In this report, an Ishikawa diagram is used to demonstrate how to relate potential causes of a major presenting problem in a clinical setting. This tool can be used by teams in problem-based learning or in self-directed learni...

  13. Establishment of human patient-derived endometrial cancer xenografts in NOD scid gamma mice for the study of invasion and metastasis.

    Directory of Open Access Journals (Sweden)

    Kenji Unno

    Full Text Available Most endometrial cancers are detected early and have a good prognosis, while some endometrial cancers are highly invasive, metastasize early, and respond suboptimally to therapy. Currently, appropriate model systems to study the aggressive nature of these tumors are lacking. The objective of this study was to establish a mouse xenograft model of endometrial tumors derived from patients in order to study the biological aggressive characteristics that underlie invasion and metastasis.Endometrial tumor tissue fragments (1.5 mm × 1.5 mm from patients undergoing surgery, were transplanted under the renal capsule of NOD scid gamma mice. After 6-8 weeks, tumors were excised and serially transplanted into additional mice for propagation. Immunohistochemical analysis of the tumors was done for various tumor markers.Four cases of different subtypes of endometrial cancer were grown and propagated in mice. Three of the four tumor cases invaded into the kidneys and to adjacent organs. While all tumors exhibited minimal to no staining for estrogen receptor α, progesterone receptor staining was observed for tumor grafts. In addition, levels and localization of E-cadherin, cytokeratin and vimentin varied depending on subtype. Finally, all tumor xenografts stained positively for urokinase plasminogen activator while 3 tumor xenografts, which showed invasive characteristics, stained positively for urokinase plasminogen activator receptor.Endometrial tumors transplanted under the renal capsule exhibit growth, invasion and local spread. These tumors can be propagated and used to study aggressive endometrial cancer.

  14. Syndecan-1 knock-down in decidualized human endometrial stromal cells leads to significant changes in cytokine and angiogenic factor expression patterns

    Directory of Open Access Journals (Sweden)

    Krüssel Jan-Steffen

    2010-11-01

    Full Text Available Abstract Background Successful embryonic implantation depends on a synchronized embryo-maternal dialogue. Chemokines, such as chemokine ligand 1 (CXCL1, play essential roles in the maternal reproductive tract leading to morphological changes during decidualization, mediating maternal acceptance towards the semi-allograft embryo and induction of angiogenesis. Chemokine binding to their classical G-protein coupled receptors is essentially supported by the syndecan (Sdc family of heparan sulfate proteoglycans. The aim of this study was to identify the involvement of Sdc-1 at the embryo-maternal interface regarding changes of the chemokine and angiogenic profile of the decidua during the process of decidualization and implantation in human endometrium. Methods A stable Sdc-1 knock-down was generated in the immortalized human endometrial stromal cell line St-T1 and was named KdS1. The ability of KdS1 to decidualize was proven by Insulin-like growth factor binding 1 (IGFBP1 and prolactin (PRL confirmation on mRNA level before further experiments were carried out. Dot blot protein analyses of decidualized knock-down cells vs non-transfected controls were performed. In order to imitate embryonic implantation, decidualized KdS1 were then incubated with IL-1beta, an embryo secretion product, vs controls. Statistical analyses were performed applying the Student's t-test with p Results The induction of the Sdc-1 knock-down revealed significant changes in cytokine and angiogenic factor expression profiles of dKdS1 vs decidualized controls. Incubation with embryonic IL-1beta altered the expression patterns of KdS1 chemokines and angiogenic factors towards inflammatory-associated molecules and factors involved in matrix regulation. Conclusions Sdc-1 knock-down in human endometrial stroma cells led to fulminant changes regarding cytokine and angiogenic factor expression profiles upon decidualization and imitation of embryonic contact. Sdc-1 appears to play an

  15. 21 CFR 884.1185 - Endometrial washer.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Endometrial washer. 884.1185 Section 884.1185 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL...: Only to evaluate the endometrium, (ii) Contraindications: Pregnancy, history of uterine perforation, or...

  16. 21 CFR 884.1060 - Endometrial aspirator.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Endometrial aspirator. 884.1060 Section 884.1060 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... endometrium, and (ii) Contraindications: Pregnancy, history of uterine perforation, or a recent cesarean...

  17. 21 CFR 884.1100 - Endometrial brush.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Endometrial brush. 884.1100 Section 884.1100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL...) Indication: Only to evaluate the endometrium, and (ii) Contraindications: Pregnancy, history of uterine...

  18. Histological changes in the endometrial of pregnant Sprague ...

    African Journals Online (AJOL)

    Administrator

    2011-06-20

    Jun 20, 2011 ... This study describes a changed uterine morphometry and its ... implanted embryos was significantly lower in the Diet 3 group at 15 days of gestation The results ... Furthermore, in human endometrial, glandular diameter.

  19. Pigment epithelium derived factor inhibits the growth of human endometrial implants in nude mice and of ovarian endometriotic stromal cells in vitro.

    Directory of Open Access Journals (Sweden)

    Yanmei Sun

    Full Text Available Angiogenesis is a prerequisite for the formation and development of endometriosis. Pigment epithelium derived factor (PEDF is a natural inhibitor of angiogenesis. We previously demonstrated a reduction of PEDF in the peritoneal fluid, serum and endometriotic lesions from women with endometriosis compared with women without endometriosis. Here, we aim to investigate the inhibitory effect of PEDF on human endometriotic cells in vivo and in vitro. We found that PEDF markedly inhibited the growth of human endometrial implants in nude mice and of ovarian endometriotic stromal cells in vitro by up-regulating PEDF expression and down-regulating vascular endothelial growth factor (VEGF expression. Moreover, apoptotic index was significantly increased in endometriotic lesions in vivo and endometriotic stromal cells in vitro when treated with PEDF. In mice treated with PEDF, decreased microvessel density labeled by Von Willebrand factor but not by α-Smooth Muscle Actin was observed in endometriotic lesions. And it showed no increase in PEDF expression of the ovary and uterus tissues. These findings suggest that PEDF gene therapy may be a new treatment for endometriosis.

  20. Risks of Endometrial Cancer Screening

    Science.gov (United States)

    ... Health history and certain medicines can affect the risk of developing endometrial cancer. Anything that increases your ... have abnormal vaginal bleeding, check with your doctor. Risks of Endometrial Cancer Screening Key Points Screening tests ...

  1. Terpenoids from Zingiber officinale (Ginger induce apoptosis in endometrial cancer cells through the activation of p53.

    Directory of Open Access Journals (Sweden)

    Yang Liu

    Full Text Available Novel strategies are necessary to improve chemotherapy response in advanced and recurrent endometrial cancer. Here, we demonstrate that terpenoids present in the Steam Distilled Extract of Ginger (SDGE are potent inhibitors of proliferation of endometrial cancer cells. SDGE, isolated from six different batches of ginger rhizomes, consistently inhibited proliferation of the endometrial cancer cell lines Ishikawa and ECC-1 at IC(50 of 1.25 µg/ml. SDGE also enhanced the anti-proliferative effect of radiation and cisplatin. Decreased proliferation of Ishikawa and ECC-1 cells was a direct result of SDGE-induced apoptosis as demonstrated by FITC-Annexin V staining and expression of cleaved caspase 3. GC/MS analysis identified a total of 22 different terpenoid compounds in SDGE, with the isomers neral and geranial constituting 30-40%. Citral, a mixture of neral and geranial inhibited the proliferation of Ishikawa and ECC-1 cells at an IC(50 10 µM (2.3 µg/ml. Phenolic compounds such as gingerol and shogaol were not detected in SDGE and 6-gingerol was a weaker inhibitor of the proliferation of the endometrial cancer cells. SDGE was more effective in inducing cancer cell death than citral, suggesting that other terpenes present in SDGE were also contributing to endometrial cancer cell death. SDGE treatment resulted in a rapid and strong increase in intracellular calcium and a 20-40% decrease in the mitochondrial membrane potential. Ser-15 of p53 was phosphorylated after 15 min treatment of the cancer cells with SDGE. This increase in p53 was associated with 90% decrease in Bcl2 whereas no effect was observed on Bax. Inhibitor of p53, pifithrin-α, attenuated the anti-cancer effects of SDGE and apoptosis was also not observed in the p53(neg SKOV-3 cells. Our studies demonstrate that terpenoids from SDGE mediate apoptosis by activating p53 and should be therefore be investigated as agents for the treatment of endometrial cancer.

  2. Osteopontin Promotes Invasion, Migration and Epithelial-Mesenchymal Transition of Human Endometrial Carcinoma Cell HEC-1A Through AKT and ERK1/2 Signaling

    OpenAIRE

    Yinghua Li; Yunpeng Xie; Dan Cui; Yanni Ma; Linlin Sui; Chenyang Zhu; Hui Kong; Ying Kong

    2015-01-01

    Background/Aims: Osteopontin (OPN) is an Extracellular Matrix (ECM) molecule and is involved in many physiologic and pathologic processes, including cell adhesion, angiogenesis and tumor metastasis. OPN is a well-known multifunctional factor involved in various aspects of cancer progression, including endometrial cancer. In this study, we examined the significance of OPN in endometrial cancer. Methods: The proliferation, migration and invasion ability of HEC-1A cells were detected by Cell Cou...

  3. Genetics of Endometrial Cancers

    Directory of Open Access Journals (Sweden)

    Tsuyoshi Okuda

    2010-01-01

    Full Text Available Endometrial cancers exhibit a different mechanism of tumorigenesis and progression depending on histopathological and clinical types. The most frequently altered gene in estrogen-dependent endometrioid endometrial carcinoma tumors is PTEN. Microsatellite instability is another important genetic event in this type of tumor. In contrast, p53 mutations or Her2/neu overexpression are more frequent in non-endometrioid tumors. On the other hand, it is possible that the clear cell type may arise from a unique pathway which appears similar to the ovarian clear cell carcinoma. K-ras mutations are detected in approximately 15%–30% of endometrioid carcinomas, are unrelated to the existence of endometrial hyperplasia. A β-catenin mutation was detected in about 20% of endometrioid carcinomas, but is rare in serous carcinoma. Telomere shortening is another important type of genomic instability observed in endometrial cancer. Only non-endometrioid endometrial carcinoma tumors were significantly associated with critical telomere shortening in the adjacent morphologically normal epithelium. Lynch syndrome, which is an autosomal dominantly inherited disorder of cancer susceptibility and is characterized by a MSH2/MSH6 protein complex deficiency, is associated with the development of non-endometrioid carcinomas.

  4. Improved human endometrial stem cells differentiation into functional hepatocyte-like cells on a glycosaminoglycan/collagen-grafted polyethersulfone nanofibrous scaffold.

    Science.gov (United States)

    Khademi, Farzaneh; Ai, Jafar; Soleimani, Masoud; Verdi, Javad; Mohammad Tavangar, Seyed; Sadroddiny, Esmaeil; Massumi, Mohammad; Mahmoud Hashemi, Seyed

    2017-11-01

    Liver tissue engineering (TE) is rapidly emerging as an effective technique which combines engineering and biological processes to compensate for the shortage of damaged or destroyed liver tissues. We examined the viability, differentiation, and integration of hepatocyte-like cells on an electrospun polyethersulfone (PES) scaffold, derived from human endometrial stem cells (hEnSCs). Natural polymers were separately grafted on plasma-treated PES nanofibers, that is, collagen, heparan sulfate (HS) and collagen-HS. Galactosilated PES (PES-Gal) nanofibrous were created. The engineering and cell growth parameters were considered and compared with each sample. The cellular studies revealed increased cell survival, attachment, and normal morphology on the bioactive natural polymer-grafted scaffolds after 30 days of hepatic differentiation. The chemical and molecular assays displayed hepatocyte differentiation. These cells were also functional, showing glycogen storage, α-fetoprotein, and albumin secretion. The HS nanoparticle-grafted PES nanofibers demonstrated a high rate of cell proliferation, differentiation, and integration. Based on the observations mentioned above, engineered tissue is a good option in the future, for the commercial production of three-dimensional liver tissues for clinical purposes. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2516-2529, 2017. © 2016 Wiley Periodicals, Inc.

  5. Medroxyprogesterone acetate-treated human, primary endometrial epithelial cells reveal unique gene expression signature linked to innate immunity and HIV-1 susceptibility.

    Science.gov (United States)

    Woods, Matthew W; Zahoor, Muhammad Atif; Dizzell, Sara; Verschoor, Chris P; Kaushic, Charu

    2018-01-01

    Medroxyprogesterone acetate (MPA), a progestin-based hormonal contraceptive designed to mimic progesterone, has been linked to increased human immunodeficiency virus (HIV-1) susceptibility. Genital epithelial cells (GECs) form the mucosal lining of the female genital tract (FGT) and provide the first line of protection against HIV-1. The impact of endogenous sex hormones or MPA on the gene expression profile of GECs has not been comprehensively documented. Using microarray analysis, we characterized the transcriptional profile of primary endometrial epithelial cells grown in physiological levels of E2, P4, and MPA. Each hormone treatment altered the gene expression profile of GECs in a unique manner. Interestingly, although MPA is a progestogen, the gene expression profile induced by it was distinct from P4. MPA increased gene expression of genes related to inflammation and cholesterol synthesis linked to innate immunity and HIV-1 susceptibility. The analysis of gene expression profiles provides insights into the effects of sex hormones and MPA on GECs and allows us to posit possible mechanisms of the MPA-mediated increase in HIV-1 acquisition. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Hypoxic stress simultaneously stimulates vascular endothelial growth factor via hypoxia-inducible factor-1α and inhibits stromal cell-derived factor-1 in human endometrial stromal cells.

    Science.gov (United States)

    Tsuzuki, Tomoko; Okada, Hidetaka; Cho, Hisayuu; Tsuji, Shoko; Nishigaki, Akemi; Yasuda, Katsuhiko; Kanzaki, Hideharu

    2012-02-01

    Hypoxia of the human endometrium is a physiologic event occurring during the perimenstrual period and the local stimulus for angiogenesis. The aim of this study was to investigate the effects of hypoxic stress on the regulation of vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1 (SDF-1/CXCL12), and the potential role of hypoxia-inducible factor-1α (HIF-1α) in the endometrium. Human endometrial stromal cells (ESCs, n= 22 samples) were studied in vitro. ESCs were cultured under hypoxic and normoxic conditions and treated with cobalt chloride (CoCl₂; a hypoxia-mimicking agent) and/or echinomycin, a small-molecule inhibitor of HIF-1α activity. The mRNA levels and production of VEGF and SDF-1 were assessed by real-time PCR and ELISA, respectively. The HIF-1α protein levels were measured using western blot analysis. Hypoxia simultaneously induced the expression of mRNA and production of VEGF and attenuated the expression and production of SDF-1 from ESCs in a time-dependent manner. Similar changes were observed in the ESCs after stimulation with CoCl₂ in a dose-dependent manner. CoCl₂ significantly induced the expression of HIF-1α protein, and its highest expression was observed at 6 h. Echinomycin inhibited hypoxia-induced VEGF production without affecting the HIF-1α protein level and cell toxicity and had no effect on SDF-1 secretion (P hypoxic conditions that could influence angiogenesis in the human endometrium.

  7. Human chorionic gonadotropin triggers angiogenesis via the modulation of endometrial stromal cell responsiveness to interleukin 1: a new possible mechanism underlying embryo implantation.

    Science.gov (United States)

    Bourdiec, Amélie; Shao, Rong; Rao, C V; Akoum, Ali

    2012-09-01

    Deep functional changes occurring within the endometrium during implantation are orchestrated by embryonic and maternal signals. Human chorionic gonadotropin (hCG), a major embryonic signal, plays a critical role in the initiation and maintenance of pregnancy. Interleukin (IL) 1, one of the earliest embryonic signals, appears to exert a direct impact on the receptive endometrium and to induce major molecular changes that are essential for embryo implantation. Herein we investigate whether hCG can modulate endometrial stromal cell (ESC) receptivity to IL1 during the implantation window and assess the impact on angiogenesis in vitro. Primary cultures of ESCs from normal fertile women during the implantation window were treated for 24 h with different concentrations of hCG (0-100 ng/ml) and stimulated for 24 h with IL1B (0-0.1 ng/ml). IL1 receptors (IL1Rs), IL1R antagonist (IL1RA), and monocyte chemotactic protein (MCP) 1 were analyzed by real-time PCR, ELISA, and Western blotting. The angiogenic activity in vitro was studied using human microvascular endothelial cell line, scratch wound assay, and cell proliferation via BrdU incorporation into DNA. Human CG induced a dose-dependent imbalance in ESC receptivity to IL1 by significantly upregulating the functional signaling IL1R1 and concomitantly downregulating the decoy inhibitory IL1R2 and IL1RA upon subsequent exposure to IL1B. Prior exposure to hCG amplified MCP1 secretion by ESCs in response to IL1B and triggered the release of angiogenic activity in vitro in which MCP1 appeared to play a significant role. Overexpression of IL1R2 using cell transfection inhibited IL1 and hCG/IL1B-mediated MCP1 secretion. These findings suggest that hCG coordinates embryonic signal interaction with the maternal endometrium, and point to a new possible pathway by which it may promote embryonic growth.

  8. Phenotypic characterization of the Komeda miniature rat Ishikawa, an animal model of dwarfism caused by a mutation in Prkg2.

    Science.gov (United States)

    Tsuchida, Atsuko; Yokoi, Norihide; Namae, Misako; Fuse, Masanori; Masuyama, Taku; Sasaki, Masashi; Kawazu, Shoji; Komeda, Kajuro

    2008-12-01

    The Komeda miniature rat Ishikawa (KMI) is a spontaneous animal model of dwarfism caused by a mutation in Prkg2, which encodes cGMP-dependent protein kinase type II (cGKII). This strain has been maintained as a segregating inbred strain for the mutated allele mri. In this study, we characterized the phenotype of the KMI strain, particularly growth traits, craniofacial measurements, and organ weights. The homozygous mutant (mri/mri) animals were approximately 70% to 80% of the size of normal, heterozygous (mri/+) animals in regard to body length, weight, and naso-occipital length of the calvarium, and the retroperitoneal fat of mri/mri rats was reduced greatly. In addition, among progeny of the (BNxKMI-mri/mri)F1xKMI-mri/mri backcross, animals with the KMI phenotype (mri/mri) were easily distinguished from those showing the wild-type phenotype (mri/+) by using growth traits such as body length and weight. Genetic analysis revealed that all of the backcrossed progeny exhibiting the KMI phenotype were homozygous for the KMI allele in the 1.2-cM region between D14Rat5 and D14Rat80 on chromosome 14, suggesting strongly that mri acts in a completely recessive manner. The KMI strain is the first and only rat model with a confirmed mutation in Prkg2 and is a valuable model for studying dwarfism and longitudinal growth traits in humans and for functional studies of cGKII.

  9. Progesterone inhibits epithelial-to-mesenchymal transition in endometrial cancer.

    Directory of Open Access Journals (Sweden)

    Paul H van der Horst

    Full Text Available BACKGROUND: Every year approximately 74,000 women die of endometrial cancer, mainly due to recurrent or metastatic disease. The presence of tumor infiltrating lymphocytes (TILs as well as progesterone receptor (PR positivity has been correlated with improved prognosis. This study describes two mechanisms by which progesterone inhibits metastatic spread of endometrial cancer: by stimulating T-cell infiltration and by inhibiting epithelial-to-mesenchymal cell transition (EMT. METHODOLOGY AND PRINCIPAL FINDINGS: Paraffin sections from patients with (n = 9 or without (n = 9 progressive endometrial cancer (recurrent or metastatic disease were assessed for the presence of CD4+ (helper, CD8+ (cytotoxic and Foxp3+ (regulatory T-lymphocytes and PR expression. Progressive disease was observed to be associated with significant loss of TILs and loss of PR expression. Frozen tumor samples, used for genome-wide expression analysis, showed significant regulation of pathways involved in immunesurveillance, EMT and metastasis. For a number of genes, such as CXCL14, DKK1, DKK4, PEG10 and WIF1, quantitive RT-PCR was performed to verify up- or downregulation in progressive disease. To corroborate the role of progesterone in regulating invasion, Ishikawa (IK endometrial cancer cell lines stably transfected with PRA (IKPRA, PRB (IKPRB and PRA+PRB (IKPRAB were cultured in presence/absence of progesterone (MPA and used for genome-wide expression analysis, Boyden- and wound healing migration assays, and IHC for known EMT markers. IKPRB and IKPRAB cell lines showed MPA induced inhibition of migration and loss of the mesenchymal marker vimentin at the invasive front of the wound healing assay. Furthermore, pathway analysis of significantly MPA regulated genes showed significant down regulation of important pathways involved in EMT, immunesuppression and metastasis: such as IL6-, TGF-β and Wnt/β-catenin signaling. CONCLUSION: Intact progesterone signaling in non

  10. Progestins inhibit estradiol-induced vascular endothelial growth factor and stromal cell-derived factor 1 in human endometrial stromal cells.

    Science.gov (United States)

    Okada, Hidetaka; Okamoto, Rika; Tsuzuki, Tomoko; Tsuji, Shoko; Yasuda, Katsuhiko; Kanzaki, Hideharu

    2011-09-01

    To investigate whether 17β-estradiol (E(2)) and progestins exert direct effects on vascular endothelial growth factor (VEGF) and stromal cell-derived factor 1 (SDF-1/CXCL12) in human endometrial stromal cells (ESCs) and thereby to clarify the regulatory function of these local angiogenic factors in the endometrium. In vitro experiment. Research laboratory at Kansai Medical University. Fourteen patients undergoing hysterectomy for benign reasons. ESCs were cultured with E(2) and/or various clinically relevant progestins (medroxyprogesterone acetate [MPA], norethisterone [NET], levonorgestrel [LNG], dienogest [DNG], and progesterone [P]). The mRNA levels and production of VEGF and SDF-1 were assessed by real-time reverse-transcription polymerase chain reaction and ELISA, respectively. E(2) significantly induced the mRNA levels and protein production of VEGF and SDF-1 in ESCs. MPA could antagonize the E(2)-stimulated effects in a time- and dose-dependent manner, and this effect could be reversed by RU-486 (P receptor antagonist). All of the progestins (MPA, NET, LNG, and DNG; 10(-9) to 10(-7) mol/L) attenuated E(2)-induced VEGF and SDF-1 production, whereas P showed these inhibitory effects only when present in a high concentration (10(-7) mol/L). Progestins have inhibitory effects on E(2)-induced VEGF and SDF-1 in ESCs. These results may indicate a potential mechanism for action of the female sex steroids in the human endometrium that can be helpful for various clinical applications. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  11. Stem cell-like differentiation potentials of endometrial side population cells as revealed by a newly developed in vivo endometrial stem cell assay.

    Directory of Open Access Journals (Sweden)

    Kaoru Miyazaki

    Full Text Available Endometrial stem/progenitor cells contribute to the cyclical regeneration of human endometrium throughout a woman's reproductive life. Although the candidate cell populations have been extensively studied, no consensus exists regarding which endometrial population represents the stem/progenitor cell fraction in terms of in vivo stem cell activity. We have previously reported that human endometrial side population cells (ESP, but not endometrial main population cells (EMP, exhibit stem cell-like properties, including in vivo reconstitution of endometrium-like tissues when xenotransplanted into immunodeficient mice. The reconstitution efficiency, however, was low presumably because ESP cells alone could not provide a sufficient microenvironment (niche to support their stem cell activity. The objective of this study was to establish a novel in vivo endometrial stem cell assay employing cell tracking and tissue reconstitution systems and to examine the stem cell properties of ESP through use of this assay.ESP and EMP cells isolated from whole endometrial cells were infected with lentivirus to express tandem Tomato (TdTom, a red fluorescent protein. They were mixed with unlabeled whole endometrial cells and then transplanted under the kidney capsule of ovariectomized immunodeficient mice. These mice were treated with estradiol and progesterone for eight weeks and nephrectomized. All of the grafts reconstituted endometrium-like tissues under the kidney capsules. Immunofluorescence revealed that TdTom-positive cells were significantly more abundant in the glandular, stromal, and endothelial cells of the reconstituted endometrium in mice transplanted with TdTom-labeled ESP cells than those with TdTom-labeled EMP cells.We have established a novel in vivo endometrial stem cell assay in which multi-potential differentiation can be identified through cell tracking during in vivo endometrial tissue reconstitution. Using this assay, we demonstrated that ESP

  12. Endometrial proteins: a reappraisal.

    Science.gov (United States)

    Seppälä, M; Julkunen, M; Riittinen, L; Koistinen, R

    1992-06-01

    Uterine factors influence reproduction at the macro-anatomy level, and the effects of hormonal steroids on endometrial morphology are well recognized in the histopathological diagnosis of dysfunctional bleeding and infertility. During the past decade, attention has been paid to endometrial protein synthesis and secretion with respect to endocrine stimuli and implantation, and to the paracrine/autocrine effects of endometrial peptide growth factors, their binding proteins and other factors. The emphasis of this presentation is on protein secretion of the secretory endometrium, in which progesterone plays a pivotal role. Insulin-like growth factors have receptors on the endometrium, and IGF-binding proteins, stimulated by progesterone, modulate the effects of IGFs locally. Also other protein products of the secretory endometrium have been reviewed in this communication, with special emphasis on studies of a progesterone-associated endometrial protein which has many names in the literature, such as PEP, PP14, alpha 2-PEG and AUP. Extensive studies are ongoing in many laboratories to elucidate the regulation, function, interplay at tissue and cellular levels, and clinical significance of these proteins.

  13. Transforming incomplete fault tree to Ishikawa diagram as an alternative method for technology transfer

    Science.gov (United States)

    Batzias, Dimitris F.

    2012-12-01

    Fault Tree Analysis (FTA) can be used for technology transfer when the relevant problem (called 'top even' in FTA) is solved in a technology centre and the results are diffused to interested parties (usually Small Medium Enterprises - SMEs) that have not the proper equipment and the required know-how to solve the problem by their own. Nevertheless, there is a significant drawback in this procedure: the information usually provided by the SMEs to the technology centre, about production conditions and corresponding quality characteristics of the product, and (sometimes) the relevant expertise in the Knowledge Base of this centre may be inadequate to form a complete fault tree. Since such cases are quite frequent in practice, we have developed a methodology for transforming incomplete fault tree to Ishikawa diagram, which is more flexible and less strict in establishing causal chains, because it uses a surface phenomenological level with a limited number of categories of faults. On the other hand, such an Ishikawa diagram can be extended to simulate a fault tree as relevant knowledge increases. An implementation of this transformation, referring to anodization of aluminium, is presented.

  14. Using an Ishikawa diagram as a tool to assist memory and retrieval of relevant medical cases from the medical literature.

    Science.gov (United States)

    Wong, Kam Cheong

    2011-03-29

    Studying medical cases is an effective way to enhance clinical reasoning skills and reinforce clinical knowledge. An Ishikawa diagram, also known as a cause-and-effect diagram or fishbone diagram, is often used in quality management in manufacturing industries.In this report, an Ishikawa diagram is used to demonstrate how to relate potential causes of a major presenting problem in a clinical setting. This tool can be used by teams in problem-based learning or in self-directed learning settings.An Ishikawa diagram annotated with references to relevant medical cases and literature can be continually updated and can assist memory and retrieval of relevant medical cases and literature. It could also be used to cultivate a lifelong learning habit in medical professionals.

  15. Using an Ishikawa diagram as a tool to assist memory and retrieval of relevant medical cases from the medical literature

    Directory of Open Access Journals (Sweden)

    Wong Kam Cheong

    2011-03-01

    Full Text Available Abstract Studying medical cases is an effective way to enhance clinical reasoning skills and reinforce clinical knowledge. An Ishikawa diagram, also known as a cause-and-effect diagram or fishbone diagram, is often used in quality management in manufacturing industries. In this report, an Ishikawa diagram is used to demonstrate how to relate potential causes of a major presenting problem in a clinical setting. This tool can be used by teams in problem-based learning or in self-directed learning settings. An Ishikawa diagram annotated with references to relevant medical cases and literature can be continually updated and can assist memory and retrieval of relevant medical cases and literature. It could also be used to cultivate a lifelong learning habit in medical professionals.

  16. Endometrial Polyps and Benign Endometrial Hyperplasia Present Increased Prevalence of DNA Fragmentation Factors 40 and 45 (DFF40 and DFF45) Together With the Antiapoptotic B-Cell Lymphoma (Bcl-2) Protein Compared With Normal Human Endometria.

    Science.gov (United States)

    Banas, Tomasz; Pitynski, Kazimierz; Mikos, Marcin; Cielecka-Kuszyk, Joanna

    2017-09-13

    DNA fragmentation factor 40 (DFF40) is a key executor of apoptosis. It localizes to the nucleus together with DNA fragmentation factor 45 (DFF45), which acts as a DFF40 inhibitor and chaperone. B-cell lymphoma (Bcl-2) protein is a proven antiapoptotic factor present in the cytoplasm. In this study, we aimed to investigate DFF40, DFF45, and Bcl-2 immunoexpression in endometrial polyps (EPs) and benign endometrial hyperplasia (BEH) tissue compared with that in normal proliferative endometrium (NPE) and normal secretory endometrium (NSE) as well as normal post menopausal endometrium (NAE). This study used archived samples from 65 and 62 cases of EPs and BEH, respectively. The control group consisted of 52 NPE, 54 NSE, and 54 NAE specimens. Immunohistochemistry was used to detect DFF40, DFF45, and Bcl-2. DFF40, DFF45, and Bcl-2 were more highly expressed in the glandular layer of EPs and BEH compared with the stroma, and this was not influenced by menopausal status. Both glandular and stromal expression of DFF40, DFF45, and Bcl-2 were significantly higher in EPs compared with NPE, NSE, and NAE. Glandular BEH tissue showed significantly higher DFF40, DFF45, and Bcl-2 expression than in NPE, NSE, and NAE. No differences in the glandular expression of DFF40, DFF45, and Bcl-2 were observed between EP and BEH tissues, while Bcl-2 stromal expression in BEH was significantly lower than in EPs. Glandular, menopause-independent DFF40, DFF45, and Bcl-2 overexpression may play an important role in the pathogenesis of EPs and BEH.

  17. Prostaglandin receptor EP3 regulates cell proliferation and migration with impact on survival of endometrial cancer patients.

    Science.gov (United States)

    Zhu, Junyan; Trillsch, Fabian; Mayr, Doris; Kuhn, Christina; Rahmeh, Martina; Hofmann, Simone; Vogel, Marianne; Mahner, Sven; Jeschke, Udo; von Schönfeldt, Viktoria

    2018-01-02

    Prostaglandin E2 (PGE2) receptor 3 (EP3) regulates tumor cell proliferation, migration, and invasion in numerous cancers. The role of EP3 as a prognostic biomarker in endometrial cancer remains unclear. The primary aim of this study was to analyze the prognostic significance of EP3 expression in endometrial cancer. We analyzed the EP3 expression of 140 endometrial carcinoma patients by immunohistochemistry. RL95-2 endometrial cancer cell line was chosen from four endometrial cancer cell lines (RL95-2, Ishikawa, HEC-1-A, and HEC-1-B) according to EP3 expression level. Treated with PGE2 and EP3 antagonist, RL95-2 cells were investigated by MTT, BrdU, and wound healing assay for functional assessment of EP3. EP3 staining differed significantly according to WHO tumor grading in both whole cohort (p = 0.01) and the subgroup of endometrioid carcinoma (p = 0.01). Patients with high EP3 expression in their respective tumors had impaired progression-free survival as well as overall survival in both cohorts above. EP3 expression in the overall cohort was identified as an independent prognostic marker for progression-free survival (HR 1.014, 95%CI 1.003-1.024, p = 0.01) when adjusted for age, stage, grading, and recurrence. Treatment with EP3 antagonists induced upregulation of estrogen receptor β and decreased activity of Ras and led to attenuated proliferation and migration of RL95-2 cells. EP3 seems to play a crucial role in endometrial cancer progression. In the context of limited systemic treatment options for endometrial cancer, this explorative analysis identifies EP3 as a potential target for diagnostic workup and therapy.

  18. Inhibitor of PI3K/Akt Signaling Pathway Small Molecule Promotes Motor Neuron Differentiation of Human Endometrial Stem Cells Cultured on Electrospun Biocomposite Polycaprolactone/Collagen Scaffolds.

    Science.gov (United States)

    Ebrahimi-Barough, Somayeh; Hoveizi, Elham; Yazdankhah, Meysam; Ai, Jafar; Khakbiz, Mehrdad; Faghihi, Faezeh; Tajerian, Roksana; Bayat, Neda

    2017-05-01

    Small molecules as useful chemical tools can affect cell differentiation and even change cell fate. It is demonstrated that LY294002, a small molecule inhibitor of phosphatidylinositol 3-kinase (PI3K)/Akt signal pathway, can inhibit proliferation and promote neuronal differentiation of mesenchymal stem cells (MSCs). The purpose of this study was to investigate the differentiation effect of Ly294002 small molecule on the human endometrial stem cells (hEnSCs) into motor neuron-like cells on polycaprolactone (PCL)/collagen scaffolds. hEnSCs were cultured in a neurogenic inductive medium containing 1 μM LY294002 on the surface of PCL/collagen electrospun fibrous scaffolds. Cell attachment and viability of cells on scaffolds were characterized by scanning electron microscope (SEM) and 3-(4,5-dimethylthiazoyl-2-yl)2,5-diphenyltetrazolium bromide (MTT) assay. The expression of neuron-specific markers was assayed by real-time PCR and immunocytochemistry analysis after 15 days post induction. Results showed that attachment and differentiation of hEnSCs into motor neuron-like cells on the scaffolds with Ly294002 small molecule were higher than that of the cells on tissue culture plates as control group. In conclusion, PCL/collagen electrospun scaffolds with Ly294002 have potential for being used in neural tissue engineering because of its bioactive and three-dimensional structure which enhances viability and differentiation of hEnSCs into neurons through inhibition of the PI3K/Akt pathway. Thus, manipulation of this pathway by small molecules can enhance neural differentiation.

  19. High throughput, cell type-specific analysis of key proteins in human endometrial biopsies of women from fertile and infertile couples

    Science.gov (United States)

    Leach, Richard E.; Jessmon, Philip; Coutifaris, Christos; Kruger, Michael; Myers, Evan R.; Ali-Fehmi, Rouba; Carson, Sandra A.; Legro, Richard S.; Schlaff, William D.; Carr, Bruce R.; Steinkampf, Michael P.; Silva, Susan; Leppert, Phyllis C.; Giudice, Linda; Diamond, Michael P.; Armant, D. Randall

    2012-01-01

    BACKGROUND Although histological dating of endometrial biopsies provides little help for prediction or diagnosis of infertility, analysis of individual endometrial proteins, proteomic profiling and transcriptome analysis have suggested several biomarkers with altered expression arising from intrinsic abnormalities, inadequate stimulation by or in response to gonadal steroids or altered function due to systemic disorders. The objective of this study was to delineate the developmental dynamics of potentially important proteins in the secretory phase of the menstrual cycle, utilizing a collection of endometrial biopsies from women of fertile (n = 89) and infertile (n = 89) couples. METHODS AND RESULTS Progesterone receptor-B (PGR-B), leukemia inhibitory factor, glycodelin/progestagen-associated endometrial protein (PAEP), homeobox A10, heparin-binding EGF-like growth factor, calcitonin and chemokine ligand 14 (CXCL14) were measured using a high-throughput, quantitative immunohistochemical method. Significant cyclic and tissue-specific regulation was documented for each protein, as well as their dysregulation in women of infertile couples. Infertile patients demonstrated a delay early in the secretory phase in the decline of PGR-B (P localization provided important insights into the potential roles of these proteins in normal and pathological development of the endometrium that is not attainable from transcriptome analysis, establishing a basis for biomarker, diagnostic and targeted drug development for women with infertility. PMID:22215622

  20. Osteopontin Promotes Invasion, Migration and Epithelial-Mesenchymal Transition of Human Endometrial Carcinoma Cell HEC-1A Through AKT and ERK1/2 Signaling.

    Science.gov (United States)

    Li, Yinghua; Xie, Yunpeng; Cui, Dan; Ma, Yanni; Sui, Linlin; Zhu, Chenyang; Kong, Hui; Kong, Ying

    2015-01-01

    Osteopontin (OPN) is an Extracellular Matrix (ECM) molecule and is involved in many physiologic and pathologic processes, including cell adhesion, angiogenesis and tumor metastasis. OPN is a well-known multifunctional factor involved in various aspects of cancer progression, including endometrial cancer. In this study, we examined the significance of OPN in endometrial cancer. The proliferation, migration and invasion ability of HEC-1A cells were detected by Cell Counting Kit-8 (CCK-8), Wound scratch assay and transwell. Western blots were employed to detect the expression of Matrix metalloproteinase-2 (MMP-2) and epithelial-mesenchymal transition (EMT)-related factors in HEC-1A cells treated with rhOPN. rhOPN promotes cell proliferation, migration and invasion in HEC-1A cells. rhOPN influenced EMT-related factors and MMP-2 expression in HEC-1A cells. rhOPN promoted HEC-1A cells migration, invasion and EMT through protein kinase B (PKB/AKT) and Extracellular regulated protein kinases (ERK1/2) signaling pathway. These results may open up a novel therapeutic strategy for endometrial cancer: namely, rhOPN have important roles in controlling growth of endometrial of cancer cells and suggest a novel target pathway for treatment of this cancer. © 2015 The Author(s) Published by S. Karger AG, Basel.

  1. Osteopontin Promotes Invasion, Migration and Epithelial-Mesenchymal Transition of Human Endometrial Carcinoma Cell HEC-1A Through AKT and ERK1/2 Signaling

    Directory of Open Access Journals (Sweden)

    Yinghua Li

    2015-10-01

    Full Text Available Background/Aims: Osteopontin (OPN is an Extracellular Matrix (ECM molecule and is involved in many physiologic and pathologic processes, including cell adhesion, angiogenesis and tumor metastasis. OPN is a well-known multifunctional factor involved in various aspects of cancer progression, including endometrial cancer. In this study, we examined the significance of OPN in endometrial cancer. Methods: The proliferation, migration and invasion ability of HEC-1A cells were detected by Cell Counting Kit-8 (CCK-8, Wound scratch assay and transwell. Western blots were employed to detect the expression of Matrix metalloproteinase-2 (MMP-2 and epithelial-mesenchymal transition (EMT-related factors in HEC-1A cells treated with rhOPN. Results: rhOPN promotes cell proliferation, migration and invasion in HEC-1A cells. rhOPN influenced EMT-related factors and MMP-2 expression in HEC-1A cells. rhOPN promoted HEC-1A cells migration, invasion and EMT through protein kinase B (PKB/AKT and Extracellular regulated protein kinases (ERK1/2 signaling pathway. Conclusions: These results may open up a novel therapeutic strategy for endometrial cancer: namely, rhOPN have important roles in controlling growth of endometrial of cancer cells and suggest a novel target pathway for treatment of this cancer.

  2. Increased expression of resistin in ectopic endometrial tissue of women with endometriosis.

    Science.gov (United States)

    Oh, Yoon Kyung; Ha, Young Ran; Yi, Kyong Wook; Park, Hyun Tae; Shin, Jung-Ho; Kim, Tak; Hur, Jun-Young

    2017-11-01

    Inflammation is a key process in the establishment and progression of endometriosis. Resistin, an adipocytokine, has biological properties linked to immunologic functions, but its role in endometriosis is unclear. Resistin gene expression was examined in eutopic and ectopic endometrial tissues from women with (n=25) or without (n=25) endometriosis. Resistin mRNA and protein levels were determined in endometrial tissue using quantitative real-time reverse transcription PCR and Western blotting, following adipokine profiling arrays. Resistin protein was detected in human endometrial tissues using an adipokine array test. Resistin mRNA and protein levels were significantly higher in ectopic endometrial tissue of patients with endometriosis than in normal eutopic endometrial tissue. Our results indicate that resistin is differentially expressed in endometrial tissues from women with endometriosis and imply a role for resistin in endometriosis-associated pelvic inflammation. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Modified Ishikawa Diagram as a Tool for Knowledge-Mapping of Agronomic Practices

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    Petr Kedaj

    2015-12-01

    Full Text Available This article describes a novel method of graphical representation of agronomic practices in crop production. The influence of initial factors, the need to follow a chronology of individual operations and the possibility of using this information for creating a knowledge base are all considered in the method designed. Consequently, alternate methods of knowledge mapping are described: Mind maps, conceptual maps, cognitive maps as well as Ishikawa diagram, which is the main inspiration for our method. These established methods of knowledge mapping have been confronted with the method proposed by our research team using a qualitative survey. Results of this study suggest a high potential of use of our method in agronomy. At the end of this article, we propose additional steps for possible improvements in usability of the method described.

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

    Energy Technology Data Exchange (ETDEWEB)

    Du, Gui-Qiang; Zhou, Long; Chen, Xiao-Yue [Department of Obstetrics and Gynecology, The International Peace Maternity and Child Health Hospital of the China Welfare Institute Affiliated to Shanghai Jiao Tong University, 910, Hengshan Road, Shanghai (China); Wan, Xiao-Ping, E-mail: wanxiaoping61@126.com [Department of Obstetrics and Gynecology, The International Peace Maternity and Child Health Hospital of the China Welfare Institute Affiliated to Shanghai Jiao Tong University, 910, Hengshan Road, Shanghai (China); He, Yin-Yan [Department of Obstetrics and Gynecology, Shanghai First People' s Hospital, Shanghai Jiao Tong University, Shanghai (China)

    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.

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

    International Nuclear Information System (INIS)

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

    2012-01-01

    Highlights: ► We assessed hydroxytamoxifen (OHT) effects in two endometrial cancer cell lines. ► GPR30 mediates the proliferative effects induced by OHT. ► GPR30 mediates the invasive effects induced by OHT. ► 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, 17β-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.

  6. Endometrial haemostasis and menstruation.

    Science.gov (United States)

    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. Endometrial Intraepithelial Neoplasia (EIN In An Endometrial Polyp

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    Devic Ana

    2015-12-01

    Full Text Available Endometrial intraepithelial neoplasia (EIN is a monoclonal neoplastic cell proliferation of the endometrium associated with a significantly increased risk of endometrioid endometrial adenocarcinoma. We herein present the case of a 58-year-old female patient who underwent a hysterectomy with bilateral salpingo-oophorectomy because of the existence of endometrial intraepithelial neoplasia in an endometrial polyp. The patient had irregular uterine bleeding, which lasted 10 days. An endometrial polyp was diagnosed by ultrasound examination. The polyp was located in the isthmus of the uterus, on the back wall, and measured 32 mm × 25 mm. The patient underwent fractional dilation and curettage, and the specimens were subjected to a histopathological examination. The histopathological findings were EIN, endometrioid type, a focus of which was found within the endometrial polyps, as well as the endometrial polyp and proliferative endometrium. The endocervical tissue was normal. Given the age of the patient and the histopathological findings, she underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy. The final histopathological findings were EIN, endometrioid type with a focus found within the endometrial polyp; endometrial polyp; simple hyperplasia; chronic inflammation of the uterine cervix; hyperkeratosis of the cervical squamous epithelium; and cervicitis chronica. There was also hydrosalpinx of the left fallopian tube, and cystic follicles in the left ovary. There was no significant morphological change in the right ovary or fallopian tube. The surgical and postoperative course were normal. The patient was sent home on the fifth postoperative day in good general condition. A check-up performed one month after surgery showed normal findings.

  8. Endometrial cancer: magnetic resonance imaging.

    Science.gov (United States)

    Manfredi, R; Gui, B; Maresca, G; Fanfani, F; Bonomo, L

    2005-01-01

    Carcinoma of the endometrium is the most common invasive gynecologic malignancy of the female genital tract. Clinically, patients with endometrial carcinoma present with abnormal uterine bleeding. The role of magnetic resonance imaging (MRI) in endometrial carcinoma is disease staging and treatment planning. MRI has been shown to be the most valuable imaging mod-ality in this task, compared with endovaginal ultrasound and computed tomography, because of its intrinsic contrast resolution and multiplanar capability. MRI protocol includes axial T1-weighted images; axial, sagittal, and coronal T2-weighted images; and dynamic gadolinium-enhanced T1-weighted imaging. MR examination is usually performed in the supine position with a phased array multicoil using a four-coil configuration. Endometrial carcinoma is isointense with the normal endometrium and myometrium on noncontrast T1-weighted images and has a variable appearance on T2-weighted images demonstrating heterogeneous signal intensity. The appearance of noninvasive endometrial carcinoma on MRI is characterized by a normal or thickened endometrium, with an intact junctional zone and a sharp tumor-myometrium interface. Invasive endometrial carcinoma is characterized disruption or irregularity of the junctional zone by intermediate signal intensity mass on T2-weighted images. Invasion of the cervical stroma is diagnosed when the low signal intensity cervical stroma is disrupted by the higher signal intensity endometrial carcinoma. MRI in endometrial carcinoma performs better than other imaging modalities in disease staging and treatment planning. Further, the accuracy and the cost of MRI are equivalent to those of surgical staging.

  9. Fisetin induces G2/M phase cell cycle arrest by inactivating cdc25C-cdc2 via ATM-Chk1/2 activation in human endometrial cancer cells

    Directory of Open Access Journals (Sweden)

    Zhan-Ying Wang

    2015-06-01

    Full Text Available Endometrial cancer is one of the most prevalent gynaecological malignancies where, currently available therapeutic options remain limited. Recently phytochemicals are exploited for their efficiency in cancer therapy. The present study investigates the anti-proliferative effect of fisetin, a flavonoid on human endometrial cancer cells (KLE and Hec1 A. Fisetin (20-100 µM effectively reduced the viability of Hec1 A and KLE cells and potentially altered the cell population at G2/M stage. Expression levels of the cell cycle proteins (cyclin B1, p-Cdc2, p-Cdc25C, p-Chk1, Chk2, p-ATM, cyclin B1, H2AX, p21 and p27 were analyzed. Fisetin suppressed cyclin B1 expression and caused inactiva-tion of Cdc25C and Cdc2 by increasing their phosphorylation levels and further activated ATM, Chk1 and Chk2. Increased levels of p21 and p27 were observed as well. These results suggest that fisetin induced G2/M cell cycle arrest via inactivating Cdc25c and Cdc2 through activation of ATM, Chk1 and Chk2.

  10. Nitric oxide induces segregation of decay accelerating factor (DAF or CD55) from the membrane lipid-rafts and its internalization in human endometrial cells.

    Science.gov (United States)

    Banadakoppa, Manu; Goluszko, Pawel; Liebenthal, Daniel; Yallampalli, Chandra

    2012-10-01

    Recent studies suggest that DAF (decay accelerating factor), a complement regulatory protein, present in lipid rafts, is utilized by Dr fimbriated Escherichia coli for their binding and internalization. Previous studies in our laboratory have shown that NO (nitric oxide) can reduce the invasion of Dr(+) E. coli and the severity of uterine infection in pregnant rats. Also, the expression level of DAF both at the mRNA and protein levels has been shown to be reduced by NO. Therefore NO mediated down-regulation of DAF appears to be an important factor in reducing the susceptibility to E. coli infection. However, it is unclear if NO can actually modulate the membrane association of DAF and therefore initial bacterial binding to cells. We found that NO induces the delocalization of DAF from the G(M1)-rich lipid rafts. Using biochemical and cell biological approaches in a uterine epithelial cell model (Ishikawa cells), DAF accumulates in caveolae upon exposure to NO. Interaction of DAF with the caveolar protein, caveolin1, leads to their internalization by endosomes. NO-induced delocalization of DAF from the lipid raft and its accumulation in caveolae are mediated through a cGMP (cyclic guanosine monophosphate) pathway. The acute localized synthesis of NO and its influence on DAF localization may represent an important unrecognized phenomenon of host defence against Dr(+) E. coli bacteria, as well as many disease conditions that involve complement system.

  11. An Ecological Survey of Mosquitoes and the Distribution of Japanese Encephalitis Virus in Ishikawa Prefecture, Japan, between 2010 and 2014.

    Science.gov (United States)

    Murakami, Manabu; Hori, Kiyoe; Kitagawa, Yoko; Oikawa, Yosaburo; Kamimura, Kiyoshi; Takegami, Tsutomu

    2017-07-24

    Japanese encephalitis virus (JEV) is a flavivirus, responsible for over 30,000 annual cases of encephalitis worldwide, with a mortality rate of approximately 30%. Therefore, it is important to examine the distribution of mosquitos carrying JEV in the fields, even though recently, the number of Japanese encephalitis cases has been approximately 5 per year in Japan. We report the seasonal dynamics of mosquitoes between 2010 and 2014 in Ishikawa Prefecture, Japan. We collected 39,308 female adult mosquitoes, 98.2% of which were classified as Culex tritaeniorhynchus Giles. We identified JEV genomic RNA belonging to genotype 1 from the homogenate of Cx. tritaeniorhynchus, collected during our study using reverse transcription-PCR and nucleotide sequencing techniques. Our results indicate that mosquito vectors for JEV are distributed not only in areas in Ishikawa, but also throughout Japan, and the results suggest that we must be careful regarding JEV outbreaks in Japan in the future.

  12. Consumers' Attitudes towards Edible Wild Plants: A Case Study of Noto Peninsula, Ishikawa Prefecture, Japan

    Directory of Open Access Journals (Sweden)

    Bixia Chen

    2012-01-01

    Full Text Available This study explored the rural revitalizing strategy in FAO's Globally Important Agricultural Heritage System (GIAHS site in Noto Peninsula, Ishikawa Prefecture of Japan, using a case study of edible wild plants. This study assessed the current and possible future utilization of edible wild plants as one important NTFP by clarifying the attitudes of consumers and exploring the challenges of harvesting edible wild plants. Traditional ecological knowledge associated with edible wild plants and the related attitudes of consumers towards wild plants was documented. A questionnaire survey found that a majority of the respondents held positive attitude towards edible wild plants as being healthy, safe food, part of traditional dietary culture. Increasing demand of edible wild plants from urban residents aroused conflicts with local residents’ interest given that around 86% of the forested hills are private in Noto Region. Non timber forest products (NTFP extraction can be seen as a tool for creating socioeconomic relationships that are dependent on healthy, biodiverse ecosystems. It was suggested that Japanese Agricultural Cooperatives (JA and Forestry Cooperatives (FCA could be involved with GIAHS process. As important traditional dietary and ecological system, edible wild plants should be a part of GIAHS project for rural revitalization.

  13. Drugs Approved for Endometrial Cancer

    Science.gov (United States)

    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.

  14. Preclinical Studies of Chemotherapy Using Histone Deacetylase Inhibitors in Endometrial Cancer

    Directory of Open Access Journals (Sweden)

    Noriyuki Takai

    2010-01-01

    Full Text Available Because epigenetic alterations are believed to be involved in the repression of tumor suppressor genes and promotion of tumorigenesis in endometrial cancers, novel compounds endowed with a histone deacetylase (HDAC inhibitory activity are an attractive therapeutic approach. In this review, we discuss the biologic and therapeutic effects of HDAC inhibitors (HDACIs in treating endometrial cancer. HDACIs were able to mediate inhibition of cell growth, cell cycle arrest, apoptosis, and the expression of genes related to the malignant phenotype in a variety of endometrial cancer cell lines. Furthermore, HDACIs were able to induce the accumulation of acetylated histones in the chromatin of the p21WAF1 gene in human endometrial carcinoma cells. In xenograft models, some HDACIs have demonstrated antitumor activity with only few side effects. In this review, we discuss the biologic and therapeutic effects of HDACIs in treating endometrial cancer, with a special focus on preclinical studies.

  15. Brachytherapy of endometrial cancers

    International Nuclear Information System (INIS)

    Peiffert, D.; Hoffstetter, S.; Charra-Brunaud, C.

    2003-01-01

    Endometrial adenocarcinomas rank third as tumoral sites en France. The tumors are confined to the uterus in 80% of the cases. Brachytherapy has a large place in the therapeutic strategy. The gold standard treatment remains extra-fascial hysterectomy with bilateral annexiectomy and bilateral internal iliac lymph node dissection. However, after surgery alone, the rate of locoregional relapses reaches 4-20%, which is reduced to 0-5% after postoperative brachytherapy of the vaginal cuff. This postoperative brachytherapy is delivered as outpatients treatment, by 3 or 4 fractions, at high dose rate. The utero-vaginal preoperative brachytherapy remains well adapted to the tumors which involve the uterine cervix. Patients presenting a localized tumor but not operable for general reasons (< 10%) can be treated with success by exclusive irradiation, which associates a pelvic irradiation followed by an utero-vaginal brachytherapy. A high local control of about 80-90% is obtained, a little lower than surgery, with a higher risk of late complications. Last but not least, local relapses in the vaginal cuff, or in the perimeatic area, can be treated by interstitial salvage brachytherapy, associated if possible with external beam irradiation. The local control is reached in half of the patients, but metastatic dissemination is frequent. We conclude that brachytherapy has a major role in the treatment of endometrial adenocarcinomas, in combination with surgery, or with external beam irradiation for not operable patients or in case of local relapses. It should use new technologies now available including computerized after-loaders and 3D dose calculation. (authors)

  16. The prevalence of endometrial hyperplasia and endometrial cancer in women with polycystic ovary syndrome or hyperandrogenism

    DEFF Research Database (Denmark)

    Holm, Nina Sofie Lillegaard; Glintborg, Dorte; Andersen, Marianne Skovsager

    2012-01-01

    Polycystic ovary syndrome may be associated with an increased risk of endometrial hyperplasia and endometrial cancer, but substantial evidence for this remains to be established. We investigated the prevalence of endometrial hyperplasia and endometrial cancer in a well characterized group of women...... with polycystic ovary syndrome and/or clinical/biochemical hyperandrogenism....

  17. Endometrial cancer with cervical extension mimicking dual concordant endometrial and cervical malignancy by F18 FDG PET and MRI

    International Nuclear Information System (INIS)

    Yoon, Seok Nam

    2012-01-01

    A 35 year old woman with endometrial cancer and cervical extension underwent F18 FDG PET CT and MRI studies after resection of a cervical mass presumed to be cervical myoma. The patient underwent cervical myomectomy and the histopathologic report revealed poorly differentiated invasive carcinoma. Cervical cancer was ruled out because the patient had no history of sexual intercourse and was negative for human papilloma virus infection. The patient underwent radical hysterectomy, bilateral salpingo oophorectomy, pelvic and para aortic lymph node dissection, and multiple biopsies. F18 FDG PET CT showed intense FDG uptake along the cervix wall. T2 weighted MRI also revealed a mass lesion with high SI involving the anterior and posterior lips of the uterine cervix. Another area of focal increased uptake above the endometrial lesion in the left pelvic cavity was observed on PET CT and MRI, possibly due to a functioning ovary. PET CT and MRI were interpreted as showing a dual concordant malignant lesion due to separated FDG uptakes and high SI without any connection between the cervical and endometrial lesions. F18 FDG PET CT showed intense FDG uptake along the endometrium. Given the patient's history and the fact that she was not menstruating at the time of imaging, this intense uptake was interpreted as another pathologic lesion, suggesting dual primary lesions. A suspected heterogeneous mass lesion along the endometrium suggesting concordant endometrial cancer was found on MRI. Endometrial cancer with cervical extension is sometimes difficult to differentiate from primary cervical cancer. The final histopathologic report showed poorly differentiated endometrial adenocarcinoma with cervical extension, although the FDG PET CT and MRI findings were suggestive of concordant cervical and endometrial cancer. Although histopathologic confirmation is necessary for final diagnosis, MRI and FDG PET CT studies may aid in the differential diagnosis. A metastatic cervical mass from

  18. Endometrial cancer with cervical extension mimicking dual concordant endometrial and cervical malignancy by F18 FDG PET and MRI

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Seok Nam [Kwandong Univ. College of Medicine, Seoul (Korea, Republic of)

    2012-09-15

    A 35 year old woman with endometrial cancer and cervical extension underwent F18 FDG PET CT and MRI studies after resection of a cervical mass presumed to be cervical myoma. The patient underwent cervical myomectomy and the histopathologic report revealed poorly differentiated invasive carcinoma. Cervical cancer was ruled out because the patient had no history of sexual intercourse and was negative for human papilloma virus infection. The patient underwent radical hysterectomy, bilateral salpingo oophorectomy, pelvic and para aortic lymph node dissection, and multiple biopsies. F18 FDG PET CT showed intense FDG uptake along the cervix wall. T2 weighted MRI also revealed a mass lesion with high SI involving the anterior and posterior lips of the uterine cervix. Another area of focal increased uptake above the endometrial lesion in the left pelvic cavity was observed on PET CT and MRI, possibly due to a functioning ovary. PET CT and MRI were interpreted as showing a dual concordant malignant lesion due to separated FDG uptakes and high SI without any connection between the cervical and endometrial lesions. F18 FDG PET CT showed intense FDG uptake along the endometrium. Given the patient's history and the fact that she was not menstruating at the time of imaging, this intense uptake was interpreted as another pathologic lesion, suggesting dual primary lesions. A suspected heterogeneous mass lesion along the endometrium suggesting concordant endometrial cancer was found on MRI. Endometrial cancer with cervical extension is sometimes difficult to differentiate from primary cervical cancer. The final histopathologic report showed poorly differentiated endometrial adenocarcinoma with cervical extension, although the FDG PET CT and MRI findings were suggestive of concordant cervical and endometrial cancer. Although histopathologic confirmation is necessary for final diagnosis, MRI and FDG PET CT studies may aid in the differential diagnosis. A metastatic cervical mass

  19. Human endometrial milk fat globule-epidermal growth factor 8 (MFGE8) is up regulated by estradiol at the transcriptional level, and its secretion via microvesicles is stimulated by human chorionic gonadotropin (hCG)

    KAUST Repository

    Sarhan, Abbaa; Bocca, Silvina; Yu, Liang; Anderson, Sandra; Jacot, Terry; Burch, Tanya; Nyalwidhe, Julius O; Sullivan, Claretta; Kaur, Mandeep; Bajic, Vladimir B.; Oehninger, Sergio

    2013-01-01

    Conclusions: We demonstrated (i) dual effects of E2 and hCG on the regulation of MFGE8, and (ii) MFGE8 protein secretion in association with microvesicles. MFGE8 has the potential to modulate endometrial function and implantation via exocrine and/ or paracrine-autocrine effects. To the best of our knowledge, this is the first demonstration of microvesicular secretion of any regulatory protein by endometrial epithelial cells, providing initial evidence suggestive of microvesicular participation in cellular trafficking information in the non-pregnant and pregnant endometrium.

  20. Prostaglandin F2α–F-Prostanoid Receptor Signalling Promotes Neutrophil Chemotaxis via Chemokine (CXC motif) Ligand-1 in Endometrial Adenocarcinoma

    Science.gov (United States)

    Wallace, Alison E; Sales, Kurt J; Catalano, Roberto D; Anderson, Richard A; Williams, Alistair RW; Wilson, Martin R; Schwarze, Jurgen; Wang, Hongwei; Rossi, Adriano G; Jabbour, Henry N

    2009-01-01

    The prostaglandin F2α (PGF2α) receptor (FP) is elevated in endometrial adenocarcinoma. This study found that PGF2α signalling via FP regulates expression of chemokine (C-X-C motif) ligand 1 (CXCL1) in endometrial adenocarcinoma cells. Expression of CXCL1 and its receptor, CXCR2, are elevated in cancer tissue as compared to normal endometrium and localised to glandular epithelium, endothelium and stroma. Treatment of Ishikawa cells stably transfected with the FP receptor (FPS cells) with 100nM PGF2α increased CXCL1 promoter activity, mRNA and protein expression, and these effects were abolished by co-treatment of cells with FP antagonist or chemical inhibitors of Gq, EGFR and ERK. Similarly, CXCL1 was elevated in response to 100 nM PGF2α in endometrial adenocarcinoma explant tissue. CXCL1 is a potent neutrophil chemoattractant. The expression of CXCR2 colocalised to neutrophils in endometrial adenocarcinoma and increased neutrophils were present in endometrial adenocarcinoma compared with normal endometrium. Conditioned media from PGF2α-treated FPS cells stimulated neutrophil chemotaxis which could be abolished by CXCL1 protein immunoneutralisation of the conditioned media or antagonism of CXCR2. Finally, xenograft tumours in nude mice arising from inoculation with FPS cells showed increased neutrophil infiltration compared to tumours arising from wild-type cells or following treatment of mice bearing FPS tumours with CXCL1-neutralising antibody. In conclusion, our results demonstrate a novel PGF2α-FP pathway that may regulate the inflammatory microenvironment in endometrial adenocarcinoma via neutrophil chemotaxis. PMID:19549892

  1. Endometrial Receptivity Profile in Patients with Premature Progesterone Elevation on the Day of hCG Administration

    Directory of Open Access Journals (Sweden)

    Delphine Haouzi

    2014-01-01

    Full Text Available The impact of a premature elevation of serum progesterone level, the day of hCG administration in patients under controlled ovarian stimulation during IVF procedure, on human endometrial receptivity is still debated. In the present study, we investigated the endometrial gene expression profile shifts during the prereceptive and receptive secretory stage in patients with normal and elevated serum progesterone level on the day of hCG administration in fifteen patients under stimulated cycles. Then, specific biomarkers of endometrial receptivity in these two groups of patients were tested. Endometrial biopsies were performed on oocyte retrieval day and on day 3 of embryo transfer, respectively, for each patient. Samples were analysed using DNA microarrays and qRT-PCR. The endometrial gene expression shift from the prereceptive to the receptive stage was altered in patients with high serum progesterone level (>1.5 ng/mL on hCG day, suggesting accelerated endometrial maturation during the periovulation period. This was confirmed by the functional annotation of the differentially expressed genes as it showed downregulation of cell cycle-related genes. Conversely, the profile of endometrial receptivity was comparable in both groups. Premature progesterone rise alters the endometrial gene expression shift between the prereceptive and the receptive stage but does not affect endometrial receptivity.

  2. Inhibition of Wnt Signaling Pathways Impairs Chlamydia trachomatis Infection in Endometrial Epithelial Cells.

    Science.gov (United States)

    Kintner, Jennifer; Moore, Cheryl G; Whittimore, Judy D; Butler, Megan; Hall, Jennifer V

    2017-01-01

    Chlamydia trachomatis infections represent the predominant cause of bacterial sexually transmitted infections. As an obligate intracellular bacterium, C. trachomatis is dependent on the host cell for survival, propagation, and transmission. Thus, factors that affect the host cell, including nutrition, cell cycle, and environmental signals, have the potential to impact chlamydial development. Previous studies have demonstrated that activation of Wnt/β-catenin signaling benefits C. trachomatis infections in fallopian tube epithelia. In cervical epithelial cells chlamydiae sequester β-catenin within the inclusion. These data indicate that chlamydiae interact with the Wnt signaling pathway in both the upper and lower female genital tract (FGT). However, hormonal activation of canonical and non-canonical Wnt signaling pathways is an essential component of cyclic remodeling in another prominent area of the FGT, the endometrium. Given this information, we hypothesized that Wnt signaling would impact chlamydial infection in endometrial epithelial cells. To investigate this hypothesis, we analyzed the effect of Wnt inhibition on chlamydial inclusion development and elementary body (EB) production in two endometrial cell lines, Ishikawa (IK) and Hec-1B, in nonpolarized cell culture and in a polarized endometrial epithelial (IK)/stromal (SHT-290) cell co-culture model. Inhibition of Wnt by the small molecule inhibitor (IWP2) significantly decreased inclusion size in IK and IK/SHT-290 cultures ( p Wnt inhibition caused chlamydiae to become aberrant in morphology. EB formation was also impaired in IK, Hec-1B and IK/SHT-290 cultures regardless of whether Wnt inhibition occurred throughout, in the middle (24 hpi) or late (36 hpi) during the development cycle. Overall, these data lead us to conclude that Wnt signaling in the endometrium is a key host pathway for the proper development of C. trachomatis .

  3. Role of emmprin in endometrial cancer

    Directory of Open Access Journals (Sweden)

    Nakamura Keiichiro

    2012-05-01

    Full Text Available Abstract Background Extracellular matrix metalloproteinase inducer (Emmprin/CD147 is a transmembrane glycoprotein that belongs to the immunoglobulin superfamily. Enriched on the surface of many tumor cells, emmprin promotes tumor growth, invasion, metastasis and angiogenesis. We evaluated the clinical importance of emmprin and investigated its role in endometrial cancer. Methods Emmprin expression was examined in uterine normal endometrium, endometrial hyperplasia and cancer specimens by immunohistochemistry. In addition, the biological functions and inhibitory effects of an emmprin knockdown were investigated in HEC-50B and KLE endometrial cancer cell lines. Results The levels of emmprin expression were significantly increased in the endometrial cancer specimens compared with the normal endometrium and endometrial hyperplasia specimens (p p p  Conclusions The present findings suggest that low emmprin expression might be a predictor of favorable prognosis in endometrial cancer patients, and that emmprin may represent a potential therapeutic target for endometrial cancer.

  4. SOX15 regulates proliferation and migration of endometrial cancer cells.

    Science.gov (United States)

    Rui, Xiaohui; Xu, Yun; Jiang, Xiping; Guo, Caixia; Jiang, Jingting

    2017-10-31

    The study aimed to investigate the effects of Sry-like high mobility group box 15 ( SOX15 ) on proliferation and migration of endometrial cancer (EC) cells. Immunohistochemistry (IHC) was applied to determine the expression of SOX15 in EC tissues and adjacent tissues. We used cell transfection method to construct the HEC-1-A and Ishikawa cell lines with stable overexpression and low expression SOX15 Reverse-transcription quantitative real-time PCR (RT-qPCR) and Western blot were performed to examine expression of SOX15 mRNA and SOX15 protein, respectively. By conducting a series of cell proliferation assay and migration assay, we analyzed the influence of SOX15 overexpression or low expression on EC cell proliferation and migration. The expression of SOX15 mRNA and protein in EC tissues was significantly lower than that in adjacent tissues. After lentivirus-transfecting SOX15 , the expression level of SOX15 mRNA and protein was significantly increased in cells of SOX15 group, and decreased in sh- SOX15 group. Overexpression of SOX15 could suppress cell proliferation, while down-regulation of SOX15 increased cell proliferation. Flow cytometry results indicated that overexpression of SOX15 induced the ratio of cell-cycle arrest in G 1 stage. In addition, Transwell migration assay results showed that SOX15 overexpression significantly inhibited cell migration, and also down-regulation of SOX15 promoted the migration. As a whole, SOX15 could regulate the proliferation and migration of EC cells and up- regulation of SOX15 could be valuable for EC treatment. © 2017 The Author(s).

  5. GGC and StuI polymorphism on the androgen receptor gene in endometrial cancer patients

    International Nuclear Information System (INIS)

    Sasaki, Masahiro; Karube, Akihiro; Karube, Yuko; Watari, Michiko; Sakuragi, Noriaki; Fujimoto, Seiichiro; Dahiya, Rajvir

    2005-01-01

    Androgens have an anti-proliferative effect on endometrial cells. Human androgen receptor (AR) gene contains two polymorphic short tandem repeats of GGC and CAG, and a single-nucleotide polymorphism on exon 1 that is recognized by the restriction enzyme, StuI. Prior studies have shown that the lengths of the CAG repeat are inversely and linearly related to AR activity and associated with endometrial cancer. However, little is known about the GGC repeat and the StuI polymorphism of the AR gene. Thus, we investigated whether these AR polymorphisms are risk factors for endometrial cancer. To test this hypothesis, the genetic distributions of these polymorphisms were investigated in blood samples from endometrial cancer patients and healthy controls. The allelic and genotyping profiles were analyzed by polymerase chain reaction (PCR), PCR-restriction fragment length polymorphism (PCR-RFLP), and direct DNA sequencing, and analyzed statistically. The GGC repeat was significantly longer in endometrial cancer patients as compared to normal healthy controls. In general, an increased risk of endometrial cancer was found with increasing GGC repeat. The relative risk for the 17 GGC repeat was greater than 4, as compared to controls. However, the StuI polymorphism was not significantly different between patients and controls. The findings suggest that increased numbers of GGC repeat on the AR gene may be a risk factor for endometrial cancer

  6. Evidence that the endometrial microbiota has an effect on implantation success or failure.

    Science.gov (United States)

    Moreno, Inmaculada; Codoñer, Francisco M; Vilella, Felipe; Valbuena, Diana; Martinez-Blanch, Juan F; Jimenez-Almazán, Jorge; Alonso, Roberto; Alamá, Pilar; Remohí, Jose; Pellicer, Antonio; Ramon, Daniel; Simon, Carlos

    2016-12-01

    Bacterial cells in the human body account for 1-3% of total body weight and are at least equal in number to human cells. Recent research has focused on understanding how the different bacterial communities in the body (eg, gut, respiratory, skin, and vaginal microbiomes) predispose to health and disease. The microbiota of the reproductive tract has been inferred from the vaginal bacterial communities, and the uterus has been classically considered a sterile cavity. However, while the vaginal microbiota has been investigated in depth, there is a paucity of consistent data regarding the existence of an endometrial microbiota and its possible impact in reproductive function. This study sought to test the existence of an endometrial microbiota that differs from that in the vagina, assess its hormonal regulation, and analyze the impact of the endometrial microbial community on reproductive outcome in infertile patients undergoing in vitro fertilization. To identify the existence of an endometrial microbiota, paired samples of endometrial fluid and vaginal aspirates were obtained simultaneously from 13 fertile women in prereceptive and receptive phases within the same menstrual cycle (total samples analyzed n = 52). To investigate the hormonal regulation of the endometrial microbiota during the acquisition of endometrial receptivity, endometrial fluid was collected at prereceptive and receptive phases within the same cycle from 22 fertile women (n = 44). Finally, the reproductive impact of an altered endometrial microbiota in endometrial fluid was assessed by implantation, ongoing pregnancy, and live birth rates in 35 infertile patients undergoing in vitro fertilization (total samples n = 41) with a receptive endometrium diagnosed using the endometrial receptivity array. Genomic DNA was obtained either from endometrial fluid or vaginal aspirate and sequenced by 454 pyrosequencing of the V3-V5 region of the 16S ribosomal RNA (rRNA) gene; the resulting sequences were

  7. Endometrial ablation with paracervical block

    NARCIS (Netherlands)

    Penninx, Josien P. M.; Mol, Ben Willem; Bongers, Marlies Y.

    2009-01-01

    OBJECTIVE: To evaluate the safety, feasibility and efficacy of endometrial ablation under local anesthesia. STUDY DESIGN: A prospective cohort study was performed at the gynecology department of a large teaching hospital. Women with dysfunctional uterine bleeding were included to undergo NovaSure

  8. Differentiation of human endometrial stem cells into urothelial cells on a three-dimensional nanofibrous silk-collagen scaffold: an autologous cell resource for reconstruction of the urinary bladder wall.

    Science.gov (United States)

    Shoae-Hassani, Alireza; Mortazavi-Tabatabaei, Seyed Abdolreza; Sharif, Shiva; Seifalian, Alexander Marcus; Azimi, Alireza; Samadikuchaksaraei, Ali; Verdi, Javad

    2015-11-01

    Reconstruction of the bladder wall via in vitro differentiated stem cells on an appropriate scaffold could be used in such conditions as cancer and neurogenic urinary bladder. This study aimed to examine the potential of human endometrial stem cells (EnSCs) to form urinary bladder epithelial cells (urothelium) on nanofibrous silk-collagen scaffolds, for construction of the urinary bladder wall. After passage 4, EnSCs were induced by keratinocyte growth factor (KGF) and epidermal growth factor (EGF) and seeded on electrospun collagen-V, silk and silk-collagen nanofibres. Later we tested urothelium-specific genes and proteins (uroplakin-Ia, uroplakin-Ib, uroplakin-II, uroplakin-III and cytokeratin 20) by immunocytochemistry, RT-PCR and western blot analyses. Scanning electron microscopy (SEM) and histology were used to detect cell-matrix interactions. DMEM/F12 supplemented by KGF and EGF induced EnSCs to express urothelial cell-specific genes and proteins. Either collagen, silk or silk-collagen scaffolds promoted cell proliferation. The nanofibrous silk-collagen scaffolds provided a three-dimensional (3D) structure to maximize cell-matrix penetration and increase differentiation of the EnSCs. Human EnSCs seeded on 3D nanofibrous silk-collagen scaffolds and differentiated to urothelial cells provide a suitable source for potential use in bladder wall reconstruction in women. Copyright © 2013 John Wiley & Sons, Ltd.

  9. Concurrent Endometrial Carcinoma in Patients with a Curettage Diagnosis of Endometrial Hyperplasia

    Directory of Open Access Journals (Sweden)

    Yu-Li Chen

    2009-06-01

    Conclusion: When patients are diagnosed with endometrial hyperplasia, surgical intervention should be performed in those with cytological atypia and higher BMI because of the possibility of coexisting endometrial carcinoma.

  10. Sperm protein 17 is highly expressed in endometrial and cervical cancers

    International Nuclear Information System (INIS)

    Li, Fang-qiu; Liu, Qun; Han, Yan-ling; Wu, Bo; Yin, Hong-lin

    2010-01-01

    Sperm protein 17 (Sp17) is a highly conserved mammalian protein in the testis and spermatozoa and has been characterized as a tumor-associated antigen in a variety of human malignancies. Many studies have examined the role of Sp17 in tumorigenesis and the migration of malignant cells. It has been proposed as a useful target for tumor-vaccine strategies and a novel marker to define tumor subsets and predict drug response. This study aimed to investigate the expression of Sp17 in endometrial and cervical cancer specimens, its possible correlation with the pathological characteristics, and its value in the diagnosis and immunotherapy of the related cancers. The monoclonal antibodies against human Sp17 were produced as reagents for the analysis and immunohistochemistry was used to study two major kinds of paraffin-embedded gynecological cancer specimens, including 50 cases of endometrial cancer (44 adenous and 6 adenosquamous) and 31 cases of cervical cancer (15 adenous and 16 squamous). Normal peripheral endometrial and cervical tissues were used as controls. Sp17 was found in 66% (33/50) of the patients with endometrial cancer and 61% (19/31) of those with cervical cancer. Its expression was found in a heterogeneous pattern in the cancer tissues. The expression was not correlated with the histological subtype and grade of malignancy, but the staining patterns were different in endometrial and cervical cancers. The hyperplastic glands were positive for Sp17 in the normal peripheral endometrial and cervical tissues in 10% (8/81) of the patients. Sp17 is highly expressed in human endometrial and cervical cancers in a heterogeneous pattern. Although the expression frequency of Sp17 is not correlated with the histological subtype, the staining pattern may help to define endometrial and cervical cancers. Sp17 targeted immunotherapy of tumors needs more accurate validation

  11. Expression of calbindin-D28k and its regulation by estrogen in the human endometrium during the menstrual cycle

    Directory of Open Access Journals (Sweden)

    Leung Peter CK

    2011-03-01

    Full Text Available Abstract Human endometrium resists embryo implantation except during the 'window of receptivity'. A change in endometrial gene expression is required for the development of receptivity. Uterine calbindin-D28k (CaBP-28k is involved in the regulation of endometrial receptivity by intracellular Ca2+. Currently, this protein is known to be mainly expressed in brain, kidneys, and pancreas, but potential role(s of CaBP-28k in the human uterus during the menstrual cycle remain to be clarified. Thus, in this study we demonstrated the expression of CaBP-28k in the human endometrium in distinct menstrual phases. During the human menstrual cycle, uterine expression levels of CaBP-28k mRNA and protein increased in the proliferative phase and fluctuated in these tissues, compared with that observed in other phases. We assessed the effects of two sex-steroid hormones, 17beta-estradiol (E2 and progesterone (P4, on the expression of CaBP-28k in Ishikawa cells. A significant increase in the expression of CaBP-28k mRNA was observed at the concentrations of E2 (10(-9 to -7 M. In addition, spatial expression of CaBP-28k protein was detected by immunohistochemistry. CaBP-28k was abundantly localized in the cytoplasm of the luminal and glandular epithelial cells during the proliferative phases (early-, mid-, late- and early-secretory phase of menstrual cycle. Taken together, these results indicate that CaBP-28k, a uterine calcium binding protein, is abundantly expressed in the human endometrium, suggesting that uterine expression of CaBP-28k may be involved in reproductive function during the human menstrual cycle.

  12. Impact of letrozole on ultrasonographic markers of endometrial receptivity in polycystic ovary syndrome women with poor endometrial response to clomiphene citrate despite adequate ovulation

    Directory of Open Access Journals (Sweden)

    Ahmed Walid A. Morad

    2015-09-01

    Conclusion: Letrozole is an effective second-line treatment in women with inadequate endometrial response to CC, as letrozole increased endometrial thickness trilaminar pattern and improved endometrial perfusion.

  13. Regulation of insulin-like growth factor-binding protein-1 synthesis and secretion by progestin and relaxin in long term cultures of human endometrial stromal cells

    Energy Technology Data Exchange (ETDEWEB)

    Bell, S.C.; Jackson, J.A.; Ashmore, J.; Zhu, H.H.; Tseng, L. (Univ. of Leicester, (United Kingdom))

    1991-05-01

    The decidualized endometrium during the first trimester of pregnancy synthesizes and secretes a 32-kDa insulin-like growth factor-binding protein (termed hIGFBP-1) at high levels. IGFBP-1 is the major soluble protein product of this tissue and is principally localized to the differentiated endometrial stromal cell, the decidual cell. In the present study long term culture of stromal cells from the nonpregnant endometrium have been employed to elucidate the hormonal requirements for IGFBP-1 production. Immunoreactive IGFBP-1 was undetectable in control cultures. However, inclusion of medroxyprogesterone acetate (MPA) induced rates of 0.35 +/- 0.09 microgram/0.1 mg cell DNA.day after 20-30 days. In these cultures cells exhibited morphological changes consistent with decidual cell differentiation. In all cultures removal of MPA after exposure for 10-16 days, with or without subsequent inclusion of relaxin (RLX), increased production of IGFBP-1 450- to 4600-fold to rates of 150-710 micrograms/0.1 mg cell DNA.day or 26-131 micrograms/10(6) cells.day on days 24-26. The rates tended to be higher with the inclusion of RLX and were sustained in contrast to cultures without RLX, where rates fell by day 30. Individual cultures responded differently to RLX when added from the initiation of culture, with either a response similar to MPA alone or a cyclical change in production, achieving maximal rates of 190-290 micrograms/0.1 mg cell DNA.day. Cultures in which RLX alone induced high IGFBP-1 high production were obtained from endometrium during the progesterone-dominated luteal phase. In cultures exhibiting high rates of immunoreactive IGFBP-1 production, the protein represented their major secretory protein product. This was confirmed by ({sup 35}S)methionine incorporation and the presence of IGFBP-1 as the predominant protein in serum-free culture medium.

  14. Endometrial biopsy findings in postmenopausal bleeding

    International Nuclear Information System (INIS)

    Sarfraz, T.; Tariq, H.

    2007-01-01

    To study endometrial histopathology in women presenting with postmenopausal bleeding. A two-year study from January 2003 to December 2004 of 100 cases of postmenopausal bleeding was conducted at Combined Military Hospital, Sialkot. The histopathology of endometrial biopsy specimens was done to find out the causes of postmenopausal bleeding in these ladies. All these 100 patients had confirmed menopause and the average age was 55 years and above. The most common histopathological diagnosis was senile endometrial atrophy (27%), followed by simple cystic hyperplasia in (17%). Three cases of simple cystic hyperplasia had coexistent ovarian tumors. Glandular hyperplasia without atypia was seen in 6% and with atypia in 4%. Other causes were endometritis (13%), endometrial polyps (8%), proliferative phase endometrium (6%) and secretary phase endometrium (5%). Endometrial carcinoma was seen in (6%) cases, (8%) biopsy specimens were non-representative. Although senile endometrial atrophy was most commonly found in these ladies but a significant percentage of endometrial hyperplasia and endometrial cancer implies the need for investigating all cases of postmenopausal bleeding. Bimanual examination and pelvic ultrasonography should be combined with endometrial sampling so that rare pelvic pathologies may not be missed. (author)

  15. Molecular Biology and Prevention of Endometrial Cancer

    National Research Council Canada - National Science Library

    Maxwell, George L

    2006-01-01

    To increase our understanding of the molecular aberrations associated with endometrial carcinogenesis and the biologic mechanisms underlying the protective effect of oral contraceptive (OC) therapy. 1...

  16. Molecular Biology and Prevention of Endometrial Cancer

    National Research Council Canada - National Science Library

    Maxwell, George

    2003-01-01

    To increase our understanding of the molecular aberrations associated with endometrial carcinogenesis and the biologic mechanisms underlying the protective effect of oral contraceptive therapy. Methods: 1...

  17. Molecular Biology and Prevention of Endometrial Cancer

    National Research Council Canada - National Science Library

    Maxwell, George L

    2004-01-01

    To increase our understanding of the molecular aberrations associated with endometrial carcinogenesis and the biologic mechanisms underlying the protective effect of oral contraceptive therapy. Methods: 1...

  18. First record of the subfamily Anoplophilinae (Orthoptera: Rhaphidophoridae) from Russia with description of a new species of the genus Alpinanoplophilus Ishikawa, 1993.

    Science.gov (United States)

    Storozhenko, Sergey Yu

    2015-06-17

    The subfamily Anoplophilinae (Rhaphidophopridae) is recorded from Russia for the first time. Alpinanoplophilus kurilensis Storozhenko, sp. nov. is described from Kunashir Island. The holotype of the new species is deposited in the Zoological Institute of Russian Academy of Science (St. Petersburg, Russia). A revised key to the species of the genus Alpinanoplophilus Ishikawa, 1993 is provided.

  19. Role of emmprin in endometrial cancer.

    Science.gov (United States)

    Nakamura, Keiichiro; Kodama, Junichi; Hongo, Atsushi; Hiramatsu, Yuji

    2012-05-28

    Extracellular matrix metalloproteinase inducer (Emmprin/CD147) is a transmembrane glycoprotein that belongs to the immunoglobulin superfamily. Enriched on the surface of many tumor cells, emmprin promotes tumor growth, invasion, metastasis and angiogenesis. We evaluated the clinical importance of emmprin and investigated its role in endometrial cancer. Emmprin expression was examined in uterine normal endometrium, endometrial hyperplasia and cancer specimens by immunohistochemistry. In addition, the biological functions and inhibitory effects of an emmprin knockdown were investigated in HEC-50B and KLE endometrial cancer cell lines. The levels of emmprin expression were significantly increased in the endometrial cancer specimens compared with the normal endometrium and endometrial hyperplasia specimens (p emmprin expression were significantly higher than those of patients with low emmprin expression (DFS: p Emmprin knockdown by the siRNA led to cell proliferation, migration and invasion through TGF-β, EGF, NF-κB, VEGF, MMP-2, and MMP-9 expression, which in turn resulted in increased levels of E-cadherin and reduced levels of Vimentin and Snail in endometrial cancer. The present findings suggest that low emmprin expression might be a predictor of favorable prognosis in endometrial cancer patients, and that emmprin may represent a potential therapeutic target for endometrial cancer.

  20. Extrauterine Low-Grade Endometrial Stromal Sarcoma

    Directory of Open Access Journals (Sweden)

    Yu-Ju Chen

    2005-12-01

    Conclusions: Low-grade endometrial stromal sarcoma typically has an indolent clinical course and favorable prognosis. Surgical resection is the primary therapeutic approach, and adjuvant therapy with radiotherapy, chemotherapy, or progesterone therapy should be considered for the management of residual or recurrent low-grade endometrial stromal sarcomas.

  1. Evaluation of endometrial cancer epidemiology in Romania.

    Science.gov (United States)

    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.

  2. Krüppel-Like factor 9 loss-of-expression in human endometrial carcinoma links altered expression of growth-regulatory genes with aberrant proliferative response to estrogen

    Science.gov (United States)

    Endometrial cancer is the most commonly diagnosed female genital tract malignancy. Krüppel-like Factor 9 (KLF9), a member of the evolutionarily conserved Sp-family of transcription factors, is expressed in uterine stroma and glandular epithelium where it affects cellular proliferation, differenti...

  3. Production of interleukin-1alpha by human endometrial stromal cells is triggered during menses and dysfunctional bleeding and is induced in culture by epithelial interleukin-1alpha released upon ovarian steroids withdrawal.

    Science.gov (United States)

    Pretto, Chrystel M; Gaide Chevronnay, Héloïse P; Cornet, Patricia B; Galant, Christine; Delvaux, Denis; Courtoy, Pierre J; Marbaix, Etienne; Henriet, Patrick

    2008-10-01

    Endometrial breakdown during menstruation and dysfunctional bleeding is triggered by the abrupt expression of matrix metalloproteinases (MMPs), including interstitial collagenase (MMP-1). The paracrine induction of MMP-1 in stromal cells via epithelium-derived IL-1alpha is repressed by ovarian steroids. However, the control by estradiol (E) and progesterone (P) of endometrial IL-1alpha expression and bioactivity remains unknown. Variations of endometrial IL-1alpha mRNA and protein along the menstrual cycle and during dysfunctional bleeding were determined using RT-PCR, in situ hybridization, and immunolabeling. The mechanism of EP control was analyzed using culture of explants, laser capture microdissection, and purified cells. Data were compared with expression changes of IL-1beta and IL-1 receptor antagonist. IL-1alpha is synthesized by epithelial cells throughout the cycle but E and/or P prevents its release. In contrast, endometrial stromal cells produce IL-1alpha only at menses and during irregular bleeding in areas of tissue breakdown. Stromal expression of IL-1alpha, like that of MMP-1, is repressed by P (alone or with E) but triggered by epithelium-derived IL-1alpha released upon EP withdrawal. Our experiments in cultured endometrium suggest that IL-1alpha released by epithelial cells triggers the production of IL-1alpha by stromal cells in a paracrine amplification loop to induce MMP-1 expression during menstruation and dysfunctional bleeding. All three steps of this amplification cascade are repressed by EP.

  4. Endometrial thickness as a test for endometrial cancer in women with postmenopausal vaginal bleeding

    DEFF Research Database (Denmark)

    Tabor, Ann; Watt, Hilary C; Wald, Nicholas J

    2002-01-01

    OBJECTIVE: To assess the value of endometrial thickness measurement as a test for endometrial cancer in postmenopausal women with vaginal bleeding (symptomatic women). DATA SOURCES: We conducted a literature search using the MEDLINE database from 1991 to 1997, and the key words "vaginal...... ultrasonography" and "endometrial thickness measurement." The review was limited to original research reports written in English, concerning symptomatic women having vaginal ultrasonography before a diagnostic test and not receiving tamoxifen. STUDY SELECTION: A total of 48 studies were identified...

  5. MR staging of endometrial carcinoma

    International Nuclear Information System (INIS)

    Innocenti, P.; Agostini, S.; Erroi, C.; Ambrogetti, D.; Cellerini, A.; Nori, J.

    1991-01-01

    Biopsy is the technique of choice for the definitive diagnosis of endometrial carcinoma. Since lymphatic tumor spread has been demonstrated to depend on the degree of myometrial involvement, the definition of the latter with imaging techniques may significantly affect both pfognosis and therapy. We investigated, by means of MR imaging at 0.5 T, 14 patients with endometrial carcinoma, to assess both tumor stage and myometrial involvement. FIGO staging system was employed, and M parameter evaluated (M0= no myometrial involvement; M1involvement confined to the inner third; M2= Involvement confined to the middle third; M3= involvement of the whole myometrium). Another parameter was the characteristic high signal of the tumor on PD and T2W images. The patients were then operated and MR information was correlated with surgical findings. Overall diagnostic accuracy of MR imaging was 85.7% in tumor staging, and 92.2% in defining M parameter. Tumor spread into adnexa and into cervical canal was poorly demonstrated by MR imaging

  6. Staging in local endometrial carcinoma

    International Nuclear Information System (INIS)

    Thorvinger, B.; Gudmundsson, T.; Horvath, G.; Forsberg, L.; Holtaas, S.; Lund Univ.

    1989-01-01

    Possible deep (more than an inner third of the uterine wall) myometrial invasion and cervical extension of endometrial carcinoma were evaluated prospectively using magnetic resonance (MR) and transabdominal real-time sonography (US) in 20 and 10 patients, respectively. The data obtained from these examinations were compared with hysterosalpingography (HSG) and clinical modalities including hysteroscopy, sounding and histopathologic findings after surgery. The concordance of outlining cervical extension was between MR and hysteroscopy 85 per cent, and between US and hysteroscopy 50 per cent. Deep myometrial tumor invasion was suggested in 4/10 patients by US and in 6/20 by MR, and was confirmed in all but one in each group at histologic examination of the resected uterus. There were no false negative US or MR examinations. Transabdominal US did not prove accurate in defining local endometrial carcinoma (distinguishing between stages I and II), but it may be used as an additional tool in revealing myometrial invasion. MR, however, seems to refine the delineation of uterine tumor growth. (orig.)

  7. Frequency of endometrial tuberculosis in female infertility

    International Nuclear Information System (INIS)

    Yousaf, A.; Zaman, G.; Sultana, N.

    2002-01-01

    Objective: To determine the frequency of endometrial tuberculosis in infertility patients. Design: an observational analytical study. Place and Duration of Study: Military Hospital Rawalpindi and Armed Forces Institute of Pathology, Rawalpindi from August 1998 to April 1999. Subjects and Methods: Endometrial biopsies were taken from 50 cases of infertility and subjected to culture on BACTEC 460 TB instrument. Results: Tuberculous endometritis was found in 10 % (n=5) of cases. Conclusion: It was concluded that endometrial tuberculosis is not an infrequent cause of infertility in our setup. (author)

  8. Is postmenopausal endometrial fluid collection alone a risk factor for endometrial cancer?

    Science.gov (United States)

    Yegin Akcay, Gulin Feykan; Tas, Emre Erdem; Yavuz, Ayse Filiz

    2018-01-01

    To determine the usefulness of single-layer, ultrasonographic measurement of endometrial fluid collection (EFC) volume to predict endometrial pathology in asymptomatic postmenopausal patients. One hundred fifty asymptomatic postmenopausal women were analysed retrospectively from January 2012 to December 2016. After patients with endometrial hyperplasia/neoplasia were included in Group-I, and those with insufficient tissue, endometrial atrophy, or endometritis were included in Group-II; Groups one and two were compared with respect to primary (correlations between endometrial thickness and EFC volume) and secondary (correlations between demographic characteristics and EFC volume) outcomes. There was no correlation between EFC volume and single-layer endometrial thickness ( P = 0.36). Likewise, demographic characteristics were not related to EFC ( P > 0.05). However, both EFC volume and single-layer endometrial thickness were thicker in Group-I compared to Group-II (4.8 ± 1.9 mm vs . 3.7 ± 2.5 mm; and 5.7 ± 9.4 mm vs . 2.7 ± 2.5 mm, respectively) ( P values were < 0.05). Although a cutoff value for endometrial thickness and EFC volume could not be recommended based on our study findings, it should be noted that 2% is a clinically significant rate of malignancy. Thus, postmenopausal patients with EFC should be evaluated for endometrial sampling.

  9. An Analysis of Impact Factors for Positioning Performance in WLAN Fingerprinting Systems Using Ishikawa Diagrams and a Simulation Platform

    Directory of Open Access Journals (Sweden)

    Keqiang Liu

    2017-01-01

    Full Text Available Many factors influence the positioning performance in WLAN RSSI fingerprinting systems, and summary of these factors is an important but challenging job. Moreover, impact analysis on nonalgorithm factors is significant to system application and quality control but little research has been conducted. This paper analyzes and summarizes the potential impact factors by using an Ishikawa diagram considering radio signal transmitting, propagating, receiving, and processing. A simulation platform was developed to facilitate the analysis experiment, and the paper classifies the potential factors into controllable, uncontrollable, nuisance, and held-constant factors considering simulation feasibility. It takes five nonalgorithm controllable factors including APs density, APs distribution, radio signal propagating attenuation factor, radio signal propagating noise, and RPs density into consideration and adopted the OFAT analysis method in experiment. The positioning result was achieved by using the deterministic and probabilistic algorithms, and the error was presented by RMSE and CDF. The results indicate that the high APs density, signal propagating attenuation factor, and RPs density, with the low signal propagating noise level, are favorable to better performance, while APs distribution has no particular impact pattern on the positioning error. Overall, this paper has made great potential contribution to the quality control of WLAN fingerprinting solutions.

  10. A Hospital-wide Outbreak of Serratia marcescens, and Ishikawa's “Fishbone” Analysis to Support Outbreak Control

    Science.gov (United States)

    Vetter, Luzia; Schuepfer, Guido; Kuster, Stefan P.

    2016-01-01

    A nosocomial outbreak of Serratia marcescens in respiratory samples predominantly from patients in a surgical intensive care unit is reported. Most of these patients were cardiac surgical patients. Initially, a vigorous but inconclusive investigation was implemented on the basis of standardized (according the US Centers for Disease Control and Prevention) steps of outbreak investigation. Then, a systemic quality management approach with “fishbone” analysis was added. As a consequence, plausible causes for the outbreak were identified: (i) S marcescens was found on the transesophageal echocardiography probe used during cardiac surgery; and (ii) the quality of the surface disinfection was insufficient due to multiple reasons and was completely reengineered. In conclusion, in addition to the standardized steps of outbreak investigation, the complementary use of quality management tools such as the Ishikawa “fishbone” analysis is helpful for outbreak control. The complete reengineering of the disinfectant procurement and logistics is assumed to have been the most effective measure to control the described outbreak. PMID:26783861

  11. Endometrial ablation: normal appearance and complications.

    Science.gov (United States)

    Drylewicz, Monica R; Robinson, Kathryn; Siegel, Cary Lynn

    2018-03-14

    Global endometrial ablation is a commonly performed, minimally invasive technique aimed at improving/resolving abnormal uterine bleeding and menorrhagia in women. As non-resectoscopic techniques have come into existence, endometrial ablation performance continues to increase due to accessibility and decreased requirements for operating room time and advanced technical training. The increased utilization of this method translates into increased imaging of patients who have undergone the procedure. An understanding of the expected imaging appearances of endometrial ablation using different modalities is important for the abdominal radiologist. In addition, the frequent usage of the technique naturally comes with complications requiring appropriate imaging work-up. We review the expected appearance of the post-endometrial ablated uterus on multiple imaging modalities and demonstrate the more common and rare complications seen in the immediate post-procedural time period and remotely.

  12. morphological pattern of endometrial biopsies in south

    African Journals Online (AJOL)

    Method: A retrospective study was undertaken to review all cases of endometrial biopsies ... MATERIALS AND METHODS. A retrospective ... tumours, 10 (0.4%) mixed tumours, 14 (0.6%) ..... accurate and concise clinical information on the.

  13. Statin use and risk of endometrial cancer

    DEFF Research Database (Denmark)

    Sperling, Cecilie D.; Verdoodt, Freija; Friis, Soren

    2017-01-01

    INTRODUCTION: Laboratory and epidemiological evidence have suggested that statin use may protect against the development of certain cancers, including endometrial cancer. In a nationwide registry-based case-control study, we examined the association between statin use and risk of endometrial cancer....... MATERIAL AND METHODS: Cases were female residents of Denmark with a primary diagnosis of endometrial cancer during 2000-2009. For each case, we selected 15 female population controls matched on date of birth (±one month) using risk-set sampling. Ever use of statin was defined as two or more prescriptions...... on separate dates. Conditional logistic regressions were used to estimate age-matched (by design) and multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CI) for endometrial cancer associated with statin use. The multivariable-adjusted models included parity, hormone replacement therapy...

  14. Endometrial cysteine-rich secretory protein 3 is inhibited by human chorionic gonadotrophin, and is increased in the decidua of tubal ectopic pregnancy

    DEFF Research Database (Denmark)

    Horne, A W; Duncan, W C; King, A E

    2009-01-01

    Ectopic pregnancy (EP) remains a considerable cause of morbidity and occasional mortality. Currently, there is no reliable test to differentiate ectopic from intrauterine gestation. We have previously used array technology to demonstrate that differences in gene expression in decidualized...... was inversely proportional to serum hCG concentrations (P caused a reduction in CRISP-3 expression (P pregnancy of unknown...... gestation-matched women undergoing surgical termination of pregnancy (n = 8), evacuation of uterus for miscarriage (n = 6) and surgery for EP (n = 11) was subjected to quantitative RT-PCR, morphological assessment, immunohistochemistry and western blot analysis. Sera were analysed for progesterone and human...

  15. Role of emmprin in endometrial cancer

    OpenAIRE

    Nakamura, Keiichiro; Kodama, Junichi; Hongo, Atsushi; Hiramatsu, Yuji

    2012-01-01

    Abstract Background Extracellular matrix metalloproteinase inducer (Emmprin/CD147) is a transmembrane glycoprotein that belongs to the immunoglobulin superfamily. Enriched on the surface of many tumor cells, emmprin promotes tumor growth, invasion, metastasis and angiogenesis. We evaluated the clinical importance of emmprin and investigated its role in endometrial cancer. Methods Emmprin expression was examined in uterine normal endometrium, endometrial hyperplasia and cancer specimens by imm...

  16. Estrogen sulfotransferases in breast and endometrial cancers.

    Science.gov (United States)

    Pasqualini, Jorge Raul

    2009-02-01

    Estrogen sulfotransferase is significantly more active in the normal breast cell (e.g., Human 7) than in the cancer cell (e.g., MCF-7). The data suggest that in breast cancer sulfoconjugated activity is carried out by another enzyme, the SULT1A, which acts at high concentration of the substrates. In breast cancer cells sulfotransferase (SULT) activity can be stimulated by various progestins: medrogestone, promegestone, and nomegestrol acetate, as well as by tibolone and its metabolites. SULT activities can also be controlled by other substances including phytoestrogens, celecoxib, flavonoids (e.g., quercetin, resveratrol), and isoflavones. SULT expression was localized in breast cancer cells, which can be stimulated by promegestone and correlated with the increase of the enzyme activity. The estrogen sulfotransferase (SULT1E1), which acts at nanomolar concentration of estradiol, can inactivate most of this hormone present in the normal breast; however, in the breast cancer cells, the sulfotransferase denoted as SULT1A1 is mainly present, and this acts at micromolar concentrations of E(2). A correlation was postulated among breast cancer cell proliferation, the effect of various progestins, and sulfotransferase stimulation. In conclusion, it is suggested that factors involved in the stimulation of the estrogen sulfotransferases could provide new possibilities for the treatment of patients with hormone-dependent breast and endometrial cancers.

  17. The relationship of serum HE4, CP2 and HCgp-39 levels with tumor malignancy in patients with endometrial carcinoma

    Directory of Open Access Journals (Sweden)

    Yun-Xia Rao

    2017-04-01

    Full Text Available Objective: To study the relationship of serum human epididymis protein (HE4, cancer protein-2 (CP2 and human cartilage glycoprotein-39 (HCgp-39 levels with tumor malignancy in patients with endometrial carcinoma. Methods: A total of 90 patients with endometrial carcinoma treated in our hospital between May 2012 and August 2015 were collected and divided into early-to-mid (Ⅰ-Ⅲ stage endometrial carcinoma group (n=59 and advanced (Ⅳ stage endometrial carcinoma group (n=31 according to the pathological staging, and 34 patients with endometrial thickening who received uterine curettage in our hospital during the same period were selected as control group. The levels of HE4, CP2, HCgp-39 and tumor markers in serum as well as the mRNA expression of proliferation genes and invasion genes in tumor tissue were determined. Results: HE4, CP2, HCgp-39, CA125, CA19-9 and CEA levels in serum as well as Bcl2, Chk1, PIK1, HER2 and GDF-15 mRNA expression in tumor tissues of early-to-mid endometrial carcinoma group and advanced endometrial carcinoma group were significantly higher than those of control group while the miRNA-199a-3p, Bax, caspase3, BRCA1, Kiss-1 and KAI1 mRNA expression were lower than those of control group; HE4, CP2, HCgp-39, CA125, CA19-9 and CEA levels in serum as well as Bcl2, Chk1, PIK1, HER2 and GDF-15 mRNA expression in tumor tissues of advanced endometrial carcinoma group were significantly higher than those of early-to-mid endometrial carcinoma group while the miRNA-199a-3p, Bax, caspase3, BRCA1, Kiss-1 and KAI1 mRNA expression were lower than those of early-to-mid endometrial carcinoma group; serum HE4, CP2 and HCgp-39 levels were positively correlated with CA125, CA19-9, CEA, Bcl2, Chk1, PIK1, HER2 and GDF- 15, and negatively correlated with miRNA-199a-3p, Bax, caspase3, BRCA1, Kiss-1 and KAI1. Conclusion: Serum HE4, CP2 and HCgp-39 levels can directly reflect the tumor malignancy in patients with endometrial carcinoma, and are

  18. The prognostic role of classical and nonclassical MHC class I expression in endometrial cancer

    NARCIS (Netherlands)

    Bijen, C.B.; Bantema-Joppe, E.J.; de Jong, Renske; Leffers, N.; Mourits, M.J.; Eggink, Henk F.; van der Zee, A.G.; Hollema, H.; de Bock, G.H.; Nijman, H.W.

    2010-01-01

    The aim of this study was to investigate classical MHC class I and nonclassical MHC (human leukocyte antigen-G [HLA-GJ) expression in a large cohort of patients with endometrial cancer, to determine the prognostic value of these cell surface markers and their relation with clinicopathological

  19. New trial evaluates investigational drug for endometrial and breast cancers | Center for Cancer Research

    Science.gov (United States)

    A new clinical trial is testing ONC201, an investigational drug that in laboratory studies has been shown to kill breast and endometrial cancer cells most likely by destroying mitochondria within the tumor cells. Mitochondria are the “powerhouse” of the cell, and blocking its activity may kill tumor cells and shrink tumors in human patients.

  20. A CLINICAL STUDY OF ENDOMETRIAL HISTOPATHOLOGY IN AUB AND INCIDENCE OF ENDOMETRIAL POLYP IN AUB

    Directory of Open Access Journals (Sweden)

    Renuka Devi Balakrishnan

    2016-11-01

    Full Text Available BACKGROUND Abnormal Uterine Bleeding (AUB is one of the most common menstrual complaints and a frequent indication for hysterectomy. It can be a manifestation of any number of pathological entities. Causes of AUB ranges from organic pathologies like leiomyoma, polyps, adenomyosis and malignancy to conditions like coagulopathy and drug-induced AUB and aetiologies vary in different age groups. Histopathological evaluation of endometrium is very vital to identify the cause of AUB. The objectives of this study are to, 1. To evaluate the endometrial histopathology in AUB, and 2. To estimate the incidence of endometrial polyp in AUB. MATERIALS AND METHODS This is a prospective study carried out on 120 women who presented with AUB. Endometrial samples collected were analysed for their histopathological pattern. RESULTS Out of 120 endometrial samples analysed among women of 30-39 years, proliferative endometrium was seen in 43.3% and secretory endometrium in 33.3% and endometrial polyp in 13.3%. In women of 40-49 years, proliferative endometrium in 36.8%, secretory endometrium in 30.9% and disordered proliferative endometrium was seen in 19% of women. The incidence of endometrial polyp was found to be 8.3% in our study. CONCLUSION There is an age-specific relation of abnormal endometrial histopathology. Among abnormal endometrial pathology, disordered proliferative endometrium was more common in perimenopausal age group and endometrial polyps in reproductive age group. The results of this study indicate that benign endometrial histopathology is common in AUB suggesting a role for more conservative therapeutic strategies.

  1. 1α,25(OH2D3 Induces Actin Depolymerization in Endometrial Carcinoma Cells by Targeting RAC1 and PAK1

    Directory of Open Access Journals (Sweden)

    Ni Zeng

    2016-12-01

    Full Text Available Background: Cell proliferation and motility require actin reorganization, which is under control of various signalling pathways including ras-related C3 botulinum toxin substrate 1 (RAC1, p21 protein-activated kinase 1 (PAK1 and actin related protein 2 (ARP2. Tumour cell proliferation is modified by 1α,25-Dihydroxy-Vitamin D3 (1α,25(OH2D3, a steroid hormone predominantly known for its role in calcium and phosphorus metabolism. The present study explored whether 1α,25(OH2D3 modifies actin cytoskeleton in Ishikawa cells, a well differentiated endometrial carcinoma cell line. Methods: To this end, actin cytoskeleton was visualized by confocal microscopy. Globular over filamentous actin ratio was determined utilizing Western blotting and flow cytometry, transcript levels by qRT-PCR and protein abundance by immunoblotting. Results: A 24 hour treatment with 1α,25(OH2D3 (100 nM significantly decreased RAC1 and PAK1 transcript levels and activity, decreased ARP2 protein levels and depolymerized actin. The effect of 1α,25(OH2D3 on actin polymerization was mimicked by pharmacological inhibition of RAC1 and PAK1. Conclusions: 1α,25(OH2D3 leads to disruption of RAC1 and PAK1 activity with subsequent actin depolymerization of endometrial carcinoma cells.

  2. Endometrial Cancer Treatment (PDQ®)—Health Professional Version

    Science.gov (United States)

    Endometrial cancer is usually diagnosed at an early stage and can be treated with surgery. Learn about the symptoms, diagnosis, prognosis, staging, and treatment for early- and advanced-stage endometrial cancer in this expert-reviewed summary.

  3. Bilateral cornual abscess after endometrial ablation following Essure sterilization.

    NARCIS (Netherlands)

    Jansen, N.E.; Vleugels, M.P.; Kluivers, K.B.; Vierhout, M.E.

    2007-01-01

    Endometrial ablation is used extensively to treat dysfunctional bleeding. Since the introduction of Essure tubal sterilization, this permanent contraception method has been widely used. Both endometrial ablation and Essure sterilization are procedures reported to have only a few complications. We

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

    Directory of Open Access Journals (Sweden)

    Juanmahel Davila

    2015-08-01

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

  5. Rac1 Regulates Endometrial Secretory Function to Control Placental Development

    Science.gov (United States)

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

    2015-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Che, Qi; Liu, Bin-Ya; Wang, Fang-Yuan; He, Yin-Yan; Lu, Wen; Liao, Yun [Department of Obstetrics and Gynecology, Shanghai First People’s Hospital Affiliated to Shanghai Jiao Tong University, Shanghai (China); Gu, Wei, E-mail: krisgu70@163.com [Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai (China); Wan, Xiao-Ping, E-mail: wanxp@sjtu.edu.cn [Department of Obstetrics and Gynecology, Shanghai First Maternity and Infant Hospital Affiliated to Tong Ji University, Shanghai (China)

    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.

  7. Effects of Quercetin on CYP450 and Cytokines in Aroclor 1254 Injured Endometrial Cells of the Pregnant Rats

    Directory of Open Access Journals (Sweden)

    Lina Xu

    2014-01-01

    Full Text Available Polychlorinated biphenyls (PCBs are widespread persistent residual environmental pollutants, which affect seriously the growth and reproductive alterations in humans and animals. Aroclor 1254 is a commercial mixture of PCBs. Quercetin is a flavonoid, which acts on estrogen receptors and causes the development of estrogen-related diseases. In this paper, the primary cultured endometrial cells in the pregnant rats were isolated and Aroclor 1254 was used to induce the injured endometrial cells model. The cells were treated with gradient quercetin, the viability of the endometrial cells, the expressions of CYP450, the contents of TNF-α, IL-6, estradiol (E2, and progesterone (P4 were measured. It showed that the viability of the cultured endometrial cells, the expression of CYP1A1 and CYP2B1, and the contents of TNF-α, E2, and IL-6 in the injured endometrial cells increased with the treatment of quercetin. It shows that quercetin has protective effect on the injured endometrial cells in the pregnant rats, this provide a basis on herbal medicine protection for animal reproductive diseases caused by environmental endocrine disruptors.

  8. Morphological pattern of endometrial biopsies in southwestern Nigeria

    African Journals Online (AJOL)

    Background: Endometrium remains the most sensitive indicator of ovarian function and endometrial biopsy is one of the diagnostic procedures in endometrial pathology. The current study was carried out to examine the morphological pattern of endometrial biopsies in Ibadan, South-western Nigeria and compare the results ...

  9. The Effect of Endometrial Thickness on In vitro Fertilization (IVF ...

    African Journals Online (AJOL)

    The value of measuring the endometrial thickness and studying the endometrial receptivity in the context of assisted conception remains a contentious issue. A prospective analysis was carried out to determine the effect of endometrial thickness on IVF - embryo transfer / ICSI outcome in dedicated Assisted Reproductive ...

  10. Overexpression of microRNA-194 suppresses the epithelial-mesenchymal transition in targeting stem cell transcription factor Sox3 in endometrial carcinoma stem cells.

    Science.gov (United States)

    Gong, Baolan; Yue, Yan; Wang, Renxiao; Zhang, Yi; Jin, Quanfang; Zhou, Xi

    2017-06-01

    The epithelial-mesenchymal transition is the key process driving cancer metastasis. MicroRNA-194 inhibits epithelial-mesenchymal transition in several cancers and its downregulation indicates a poor prognosis in human endometrial carcinoma. Self-renewal factor Sox3 induces epithelial-mesenchymal transition at gastrulation and is also involved epithelial-mesenchymal transition in several cancers. We intended to determine the roles of Sox3 in inducing epithelial-mesenchymal transition in endometrial cancer stem cells and the possible role of microRNA-194 in controlling Sox3 expression. Firstly, we found that Sox3 and microRNA-194 expressions were associated with the status of endometrial cancer stem cells in a panel of endometrial carcinoma tissue, the CD133+ cell was higher in tumorsphere than in differentiated cells, and overexpression of microRNA-194 would decrease CD133+ cell expression. Silencing of Sox3 in endometrial cancer stem cell upregulated the epithelial marker E-cadherin, downregulated the mesenchymal marker vimentin, and significantly reduced cell invasion in vitro; overexpression of Sox3 reversed these phenotypes. Furthermore, we discovered that the expression of Sox3 was suppressed by microRNA-194 through direct binding to the Sox3 3'-untranslated region. Ectopic expression of microRNA-194 in endometrial cancer stem cells induced a mesenchymal-epithelial transition by restoring E-cadherin expression, decreasing vimentin expression, and inhibiting cell invasion in vitro. Moreover, overexpression of microRNA-194 inhibited endometrial cancer stem cell invasion or metastasis in vivo by injection of adenovirus microRNA-194. These findings demonstrate the novel mechanism by which Sox3 contributes to endometrial cancer stem cell invasion and suggest that repression of Sox3 by microRNA-194 may have therapeutic potential to suppress endometrial carcinoma metastasis. The cancer stem cell marker, CD133, might be the surface marker of endometrial cancer stem

  11. Adjuvant radiotherapy for stage I endometrial cancer.

    Science.gov (United States)

    Kong, A; Johnson, N; Cornes, P; Simera, I; Collingwood, M; Williams, C; Kitchener, H

    2007-04-18

    The role of adjuvant radiotherapy (both pelvic external beam radiotherapy and vaginal intracavity brachytherapy) in stage I endometrial cancer following total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH and BSO) remains unclear. To assess the efficacy of adjuvant radiotherapy following surgery for stage I endometrial cancer. The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CancerLit, Physician Data Query (PDQ) of National Cancer Institute. Handsearching was also carried out where appropriate. Randomised controlled trials (RCTs) which compared adjuvant radiotherapy versus no radiotherapy following surgery for patients with stage I endometrial cancer were included. Quality of the studies was assessed and data collected using a predefined data collection form. The primary endpoint was overall survival. Secondary endpoints were locoregional recurrence, distant recurrence and endometrial cancer death. Data on quality of life (QOL) and morbidity were also collected. A meta-analysis on included trials was performed using the Cochrane Collaboration Review Manager Software 4.2. The meta-analysis was performed on four trials (1770 patients). The addition of pelvic external beam radiotherapy to surgery reduced locoregional recurrence, a relative risk (RR) of 0.28 (95% confidence interval (CI) 0.17 to 0.44, p ASTEC; Lukka) are awaited. External beam radiotherapy carries a risk of toxicity and should be avoided in stage 1 endometrial cancer patients with no high risk factors.

  12. The endometrial factor in human embryo implantation

    NARCIS (Netherlands)

    Boomsma, C.M.

    2009-01-01

    The studies presented in this thesis aimed to explore the role of the endometrium in the implantation process. At present, embryo implantation is the major rate-limiting step for success in fertility treatment. Clinicians have sought to develop clinical interventions aimed at enhancing implantation

  13. Use of the Ishikawa diagram in a case-control analysis to assess the causes of a diffuse lamellar keratitis outbreak

    Directory of Open Access Journals (Sweden)

    Luis Henrique Lira

    Full Text Available ABSTRACT Purpose: To identify the causes of a diffuse lamellar keratitis (DLK outbreak using a systematic search tool in a case-control analysis. Methods: An Ishikawa diagram was used to guide physicians to determine the potential risk factors involved in this outbreak. Coherence between the occurrences and each possible cause listed in the diagram was verified, and the total number of eyes at risk was used to calculate the proportion of affected eyes. Multivariate analysis was performed using logistic regression to determine the independent effect of the risk factors, after controlling for confounders and test interactions. Results: All DLK cases were reported in 2007 between June 13 and December 21; during this period, 3,698 procedures were performed. Of the 1,682 flap-related procedures, 204 eyes of 141 individuals presented with DLK. No direct relationship was observed between the occurrence of DLK and the presence of any specific factors; however, flap-lifting enhancements, procedures performed during the morning shift, and non-use of therapeutic contact lenses after the surgery were significantly related to higher occurrence percentages of this condition. Conclusions: The Ishikawa diagram, like most quality tools, is a visualization and knowledge organization tool. This systematization allowed the investigators to thoroughly assess all the possible causes of DLK outbreak. A clear view of the entire surgical logistics permitted even more rigid management of the main factors involved in the process and, as a result, highlighted factors that deserved attention. The case-control analysis on every factor raised by the Ishikawa diagram indicated that the commonly suspected factors such as biofilm contamination of the water reservoir in autoclaves, the air-conditioning filter system, glove powder, microkeratome motor oil, and gentian violet markers were not related to the outbreak.

  14. Use of the Ishikawa diagram in a case-control analysis to assess the causes of a diffuse lamellar keratitis outbreak.

    Science.gov (United States)

    Lira, Luis Henrique; Hirai, Flávio E; Oliveira, Marivaldo; Portellinha, Waldir; Nakano, Eliane Mayumi

    2017-01-01

    To identify the causes of a diffuse lamellar keratitis (DLK) outbreak using a systematic search tool in a case-control analysis. An Ishikawa diagram was used to guide physicians to determine the potential risk factors involved in this outbreak. Coherence between the occurrences and each possible cause listed in the diagram was verified, and the total number of eyes at risk was used to calculate the proportion of affected eyes. Multivariate analysis was performed using logistic regression to determine the independent effect of the risk factors, after controlling for confounders and test interactions. All DLK cases were reported in 2007 between June 13 and December 21; during this period, 3,698 procedures were performed. Of the 1,682 flap-related procedures, 204 eyes of 141 individuals presented with DLK. No direct relationship was observed between the occurrence of DLK and the presence of any specific factors; however, flap-lifting enhancements, procedures performed during the morning shift, and non-use of therapeutic contact lenses after the surgery were significantly related to higher occurrence percentages of this condition. The Ishikawa diagram, like most quality tools, is a visualization and knowledge organization tool. This systematization allowed the investigators to thoroughly assess all the possible causes of DLK outbreak. A clear view of the entire surgical logistics permitted even more rigid management of the main factors involved in the process and, as a result, highlighted factors that deserved attention. The case-control analysis on every factor raised by the Ishikawa diagram indicated that the commonly suspected factors such as biofilm contamination of the water reservoir in autoclaves, the air-conditioning filter system, glove powder, microkeratome motor oil, and gentian violet markers were not related to the outbreak.

  15. Homozygous and heterozygous GH transgenesis alters fatty acid composition and content in the liver of Amago salmon (Oncorhynchus masou ishikawae

    Directory of Open Access Journals (Sweden)

    Manabu Sugiyama

    2012-08-01

    Growth hormone (GH transgenic Amago (Oncorhynchus masou ishikawae, containing the sockeye GH1 gene fused with metallothionein-B promoter from the same species, were generated and the physiological condition through lipid metabolism compared among homozygous (Tg/Tg and heterozygous GH transgenic (Tg/+ Amago and the wild type control (+/+. Previously, we have reported that the adipose tissue was generally smaller in GH transgenic fish compared to the control, and that the Δ-6 fatty acyl desaturase gene was down-regulated in the Tg/+ fish. However, fatty acid (FA compositions have not been measured previously in these fish. In this study we compared the FAs composition and content in the liver using gas chromatography. Eleven kinds of FA were detected. The composition of saturated and monounsaturated fatty acids (SFA and MUFA such as myristic acid (14:0, palmitoleic acid (16:1n-7, and cis-vaccenic acid (cis-18:1n-7 was significantly (P<0.05 decreased in GH transgenic Amago. On the other hand, the composition of polyunsaturated fatty acids (PUFAs such as linoleic acid (18:2n-6, arachidonic acid (20:4n-6, and docosapentaenoic acid (22:5n-3 was significantly (P<0.05 increased. Levels of serum glucose and triacylglycerol were significantly (P<0.05 decreased in the GH transgenics compared with +/+ fish. Furthermore, 3′-tag digital gene expression profiling was performed using liver tissues from Tg/Tg and +/+ fish, and showed that Mid1 interacting protein 1 (Mid1ip1, which is an important factor to activate Acetyl-CoA carboxylase (ACC, was down-regulated in Tg/Tg fish, while genes involved in FA catabolism were up-regulated, including long-chain-fatty-acid–CoA ligase 1 (ACSL1 and acyl-coenzyme A oxidase 3 (ACOX3. These data suggest that liver tissue from GH transgenic Amago showed starvation by alteration in glucose and lipid metabolism due to GH overexpression. The decrease of serum glucose suppressed Mid1ip1, and caused a decrease of de novo FA synthesis, resulting

  16. Metformin for endometrial hyperplasia: a Cochrane protocol.

    Science.gov (United States)

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

    2016-08-16

    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. 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. Dissemination of the completed review will be through the Cochrane

  17. Increased endometrial thickness in women with hypertension.

    Science.gov (United States)

    Bornstein, J; Auslender, R; Goldstein, S; Kohan, R; Stolar, Z; Abramovici, H

    2000-09-01

    We noticed an increase in endometrial thickness in women with hypertension who were treated with a combination of medications, including beta-blockers. The purpose of this study was to examine whether the endometrium of hypertensive women is thicker than that of healthy women and to determine whether endometrial thickening in hypertensive women is directly related to the antihypertensive beta-blocker treatment. We compared 3 groups of postmenopausal patients as follows: (1) women with a history of essential hypertension treated with a combination of medications, including beta-blockers; (2) women with a history of hypertension treated with a combination of medications that did not include beta-blockers; and (3) healthy women without hypertension. All patients were interviewed and examined, blood tests were performed, and endometrial thickness in the anterior-posterior diameter was measured by vaginal ultrasonography. Among the exclusion criteria were diabetes or an abnormal fasting blood glucose level, obesity, hormonal medication or replacement hormonal therapy during the previous 6 months, and a history of hormonal disturbances, infertility, or polycystic ovary syndrome. Of 45 hypertensive women enrolled in the study, 22 were treated with a beta-blocker combination medication and 23 were treated with other antihypertensive medications. They were compared with 25 healthy women. There was no statistically significant difference in endometrial thickness between women treated with medications, including beta-blockers, and those who were treated with other hypotensive agents. Twenty percent of women with hypertension and none of the healthy women had endometrium >5 mm thick (P infinity). Twenty percent of hypertensive postmenopausal women were found to have increased endometrial thickness. However, we were unable to substantiate an association between the type of treatment administered, whether beta-blockers were included, and the increase in endometrial thickness.

  18. Polymorphisms in inflammation pathway genes and endometrial cancer risk

    Science.gov (United States)

    Delahanty, Ryan J.; Xiang, Yong-Bing; Spurdle, Amanda; Beeghly-Fadiel, Alicia; Long, Jirong; Thompson, Deborah; Tomlinson, Ian; Yu, Herbert; Lambrechts, Diether; Dörk, Thilo; Goodman, Marc T.; Zheng, Ying; Salvesen, Helga B.; Bao, Ping-Ping; Amant, Frederic; Beckmann, Matthias W.; Coenegrachts, Lieve; Coosemans, An; Dubrowinskaja, Natalia; Dunning, Alison; Runnebaum, Ingo B.; Easton, Douglas; Ekici, Arif B.; Fasching, Peter A.; Halle, Mari K.; Hein, Alexander; Howarth, Kimberly; Gorman, Maggie; Kaydarova, Dylyara; Krakstad, Camilla; Lose, Felicity; Lu, Lingeng; Lurie, Galina; O’Mara, Tracy; Matsuno, Rayna K.; Pharoah, Paul; Risch, Harvey; Corssen, Madeleine; Trovik, Jone; Turmanov, Nurzhan; Wen, Wanqing; Lu, Wei; Cai, Qiuyin; Zheng, Wei; Shu, Xiao-Ou

    2013-01-01

    Background Experimental and epidemiological evidence have suggested that chronic inflammation may play a critical role in endometrial carcinogenesis. Methods To investigate this hypothesis, a two-stage study was carried out to evaluate single nucleotide polymorphisms (SNPs) in inflammatory pathway genes in association with endometrial cancer risk. In stage 1, 64 candidate pathway genes were identified and 4,542 directly genotyped or imputed SNPs were analyzed among 832 endometrial cancer cases and 2,049 controls, using data from the Shanghai Endometrial Cancer Genetics Study. Linkage disequilibrium of stage 1 SNPs significantly associated with endometrial cancer (PAsian- and European-ancestry samples. Conclusions These findings lend support to the hypothesis that genetic polymorphisms in genes involved in the inflammatory pathway may contribute to genetic susceptibility to endometrial cancer. Impact Statement This study adds to the growing evidence that inflammation plays an important role in endometrial carcinogenesis. PMID:23221126

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

    Directory of Open Access Journals (Sweden)

    Gang Feng

    2014-01-01

    Full Text Available 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.

  20. Changes of heterogeneous cell populations in the Ishikawa cell line during long-term culture: Proposal for an in vitro clonal evolution model of tumor cells.

    Science.gov (United States)

    Kasai, Fumio; Hirayama, Noriko; Ozawa, Midori; Iemura, Masashi; Kohara, Arihiro

    2016-06-01

    Genomic changes in tumor cell lines can occur during culture, leading to differences between cell lines carrying the same name. In this study, genome profiles between low and high passages were investigated in the Ishikawa 3-H-12 cell line (JCRB1505). Cells contained between 43 and 46 chromosomes and the modal number changed from 46 to 45 during culture. Cytogenetic analysis revealed that a translocation t(9;14), observed in all metaphases, is a robust marker for this cell line. Single-nucleotide polymorphism microarrays showed a heterogeneous copy number in the early passages and distinct profiles at late passages. These results demonstrate that cell culture can lead to elimination of ancestral clones by sequential selection, resulting in extensive replacement with a novel clone. Our observations on Ishikawa cells in vitro are different from the in vivo heterogeneity in which ancestral clones are often retained during tumor evolution and suggest a model for in vitro clonal evolution. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. The effect of endometrial thickness and pattern measured by ultrasonography on pregnancy outcomes during IVF-ET cycles

    Directory of Open Access Journals (Sweden)

    Zhao Jing

    2012-11-01

    Full Text Available Abstract Background To study the effect of endometrial thickness and pattern measured using ultrasound upon pregnancy outcomes in patients undergoing IVF-ET. Method One thousand nine hundred thirty-three women undergoing IVF treatment participated in the study. We assessed and recorded endometrial patterns and thickness on the day of human chorionic gonadotropin (hCG administration. Receiver operator curves (ROC were used to determine the predictive accuracy of endometrial thickness. Cycles were divided into 3 groups depending on the thickness (group 1: ≤ 7 mm; group 2: > 7 mm to ≤ 14 mm; group 3: > 14 mm. Each group was subdivided into three groups according to the endometrial pattern as follows: pattern A (a triple-line pattern consisting of a central hyperechoic line surround by two hypoechoic layers; pattern B (an intermediate isoechogenic pattern with the same reflectivity as the surrounding myometrium and a poorly defined central echogenic line; and pattern C (homogenous, hyperechogenic endometrium. Clinical outcomes such as implantation and clinical pregnancy rates were analyzed. Results The endometrial thickness predicts pregnancy outcome with high sensitivity and specificity. The cutoff value was 9 mm. The implantation rate and clinical pregnancy rate in group 3 were 39.1% and 63.5%, respectively, which were significantly higher than those in group 2 (33.8% and 52.1%, respectively and group 1 (13% and 25.5%, respectively. Among those with Pattern A, the implantation rate and clinical pregnancy rate were 35.3% and 55.2%, respectively, which were significantly higher than among women with Pattern B (32.1% and 50.9%, respectively and Pattern C (23.4% and 37.4%, respectively. In groups 1 and 3, clinical pregnancy and implantation rates did not show any significant differences between different endometrial patterns (P > 0.05, whereas in group 2, the clinical pregnancy rate and implantation rate in women with pattern A were

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

    Science.gov (United States)

    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. Copyright © 2013 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  3. Hysteroscopic Endometrial Resection in the Management of ...

    African Journals Online (AJOL)

    All women underwent hysteroscopic endometrial resection and 28 of them had hysteroscopic myomectomy. The success rate was 92.8% (65/70) after 2 years follow up. All the five women with failure of the procedure were younger ( 7 ...

  4. Serosal and Endometrial Reconstitution During Myomectomy ...

    African Journals Online (AJOL)

    Context: Myomectomy is usually performed when uterine fibroids are associated with infertility. Serosal and endometrial reconstitution are some of the subtle challenges that the gynaecologist has to deal with during myomectomy, in an attempt to minimise postoperative pelvic and intrauterine adhesions. Objective: This ...

  5. Factors Influencing Endometrial Thickness in Postmenopausal Women

    African Journals Online (AJOL)

    Background: Cut‑off values for endometrial thickness (ET) in asymptomatic postmenopausal woman have been standardized. However, there are no comprehensive studies to document how various factors can influence the ET after the age of menopause. Aim: To study the various factors influencing the ET in ...

  6. Spatial and temporal characterization of endometrial mesenchymal stem-like cells activity during the menstrual cycle

    International Nuclear Information System (INIS)

    Shan, Xu; Chan, Rachel W.S.; Ng, Ernest H.Y.; Yeung, William S.B.

    2017-01-01

    The human endometrium is a highly dynamic tissue with the ability to cyclically regenerate during the reproductive life. Endometrial mesenchymal stem-like cells (eMSCs) located throughout the endometrium have shown to functionally contribute to endometrial regeneration. In this study we examine whether the menstrual cycle stage and the location in the endometrial bilayer (superficial and deep portions of the endometrium) has an effect on stem cell activities of eMSCs (CD140b"+CD146"+ cells). Here we show the percentage and clonogenic ability of eMSCs were constant in the various stages of the menstrual cycle (menstrual, proliferative and secretory). However, eMSCs from the menstrual endometrium underwent significantly more rounds of self-renewal and enabled a greater total cell output than those from the secretory phase. Significantly more eMSCs were detected in the deeper portion of the endometrium compared to the superficial layer but their clonogenic and self-renewal activities remained similar. Our findings suggest that eMSCs are activated in the menstrual phase for the cyclical regeneration of the endometrium. - Highlights: • The percentages of endometrial mesenchymal-like stem cells (eMSCs) were constant across the menstrual cycle. • Menstruation eMSCs display superior self-renewal and long-term proliferative activities. • More eMSCs reside in the deeper portion of the endometrium than the superficial layer.

  7. Siegesbeckia orientalis Extract Inhibits TGFβ1-Induced Migration and Invasion of Endometrial Cancer Cells

    Directory of Open Access Journals (Sweden)

    Chi-Chang Chang

    2016-08-01

    Full Text Available Type II endometrial carcinoma typically exhibits aggressive metastasis and results in a poor prognosis. Siegesbeckia orientalis Linne is a traditional Chinese medicinal herb with several medicinal benefits, including the cytotoxicity against various cancers. This study investigates the inhibitory effects of S. orientalis ethanol extract (SOE on the migration and invasion of endometrial cancer cells, which were stimulated by transforming growth factor β (TGFβ. The inhibitory effects were evaluated by determining wound healing and performing the Boyden chamber assay. This study reveals that SOE can inhibit TGFβ1-induced cell wound healing, cell migration, and cell invasion in a dose-dependent manner in RL95-2 and HEC-1A endometrial cancer cells. SOE also reversed the TGFβ1-induced epithelial-mesenchymal transition, including the loss of the cell-cell junction and the lamellipodia-like structures. Western blot analysis revealed that SOE inhibited the phosphorylation of ERK1/2, JNK1/2, and Akt, as well as the expression of MMP-9, MMP-2, and u-PA in RL95-2 cells dose-dependently. The results of this investigation suggest that SOE is a potential anti-metastatic agent against human endometrial tumors.

  8. Spatial and temporal characterization of endometrial mesenchymal stem-like cells activity during the menstrual cycle

    Energy Technology Data Exchange (ETDEWEB)

    Shan, Xu [Department of Obstetrics and Gynaecology, The University of Hong Kong, Pokfulam, Hong Kong, SAR (China); Chan, Rachel W.S., E-mail: rwschan@hku.hk [Department of Obstetrics and Gynaecology, The University of Hong Kong, Pokfulam, Hong Kong, SAR (China); Centre of Reproduction, Development of Growth, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR (China); Ng, Ernest H.Y.; Yeung, William S.B. [Department of Obstetrics and Gynaecology, The University of Hong Kong, Pokfulam, Hong Kong, SAR (China); Centre of Reproduction, Development of Growth, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR (China)

    2017-01-01

    The human endometrium is a highly dynamic tissue with the ability to cyclically regenerate during the reproductive life. Endometrial mesenchymal stem-like cells (eMSCs) located throughout the endometrium have shown to functionally contribute to endometrial regeneration. In this study we examine whether the menstrual cycle stage and the location in the endometrial bilayer (superficial and deep portions of the endometrium) has an effect on stem cell activities of eMSCs (CD140b{sup +}CD146{sup +} cells). Here we show the percentage and clonogenic ability of eMSCs were constant in the various stages of the menstrual cycle (menstrual, proliferative and secretory). However, eMSCs from the menstrual endometrium underwent significantly more rounds of self-renewal and enabled a greater total cell output than those from the secretory phase. Significantly more eMSCs were detected in the deeper portion of the endometrium compared to the superficial layer but their clonogenic and self-renewal activities remained similar. Our findings suggest that eMSCs are activated in the menstrual phase for the cyclical regeneration of the endometrium. - Highlights: • The percentages of endometrial mesenchymal-like stem cells (eMSCs) were constant across the menstrual cycle. • Menstruation eMSCs display superior self-renewal and long-term proliferative activities. • More eMSCs reside in the deeper portion of the endometrium than the superficial layer.

  9. TESTIN was commonly hypermethylated and involved in the epithelial-mesenchymal transition of endometrial cancer.

    Science.gov (United States)

    Dong, Ruofan; Pu, Hong; Wang, Yuan; Yu, Jinjin; Lian, Kuixian; Mao, Caiping

    2015-05-01

    We previously reported frequent loss of TESTIN in human endometrial carcinoma, which significantly suppressed tumor proliferation and invasion. Herein, we further explored the mechanisms underlying TESTIN loss and its roles in the epithelial-mesenchymal transition (EMT, a key step for tumor spreading). Methylation-specific PCR was performed to investigate the promoter status of TESTIN in a panel of endometrial cancer and normal endometrium tissues. The expression of TESTIN mRNA was determined by real-time PCR. Up- and down-regulation of TESTIN were achieved by transient transfection with pcDNA3.1-TESTIN and shRNA-TESTIN plasmids, respectively. The EMT alterations were observed under the optical microscope and EMT-related markers were detected by real-time PCR and western blot. Compared to the control (3.6%), TESTIN was hypermethylated in 43.7% endometrial cancer tissues (p < 0.001). Moreover, TESTIN hypermethylation was significantly correlated with advanced tumor stage, deep myometrial invasion and lymphatic node metastasis. In vitro, the demethylating agent dramatically restored the expression of TESTIN. In addition, up-regulation of TESTIN significantly suppressed the EMT procedure; whereas down-regulation of TESTIN enhanced EMT. In conclusion, we demonstrated that loss of TESTIN was mainly caused by hypermethylation, which might be a potent prognostic marker. Furthermore, we proved that TESTIN significantly suppressed the EMT procedure, proposing restoration of TESTIN to be a novel therapeutic strategy for endometrial carcinoma. © 2015 APMIS. Published by John Wiley & Sons Ltd.

  10. Estrogen and high-fat diet induced alterations in C57BL/6 mice endometrial transcriptome profile

    Directory of Open Access Journals (Sweden)

    Yali Cheng

    2017-12-01

    Full Text Available Unopposed estrogen stimulation and insulin resistance are known to play important roles in endometrial cancer (EC, but the interaction between these two factors and how they contribute to endometrial lesions are not completely elucidated. To investigate the endometrial transcriptome profile and the associated molecular pathway alterations, we established an ovariectomized C57BL/6 mouse model treated with subcutaneous implantation of 17-β estradiol (E2 pellet and/or high-fat diet (HFD for 12 weeks to mimic sustained estrogen stimulation and insulin resistance. Histomorphologically, we found that both E2 and E2 + HFD groups showed markedly enlarged uterus and increased number of endometrial glands. The endometrium samples were collected for microarray assay. GO and KEGG analysis showed that genes regulated by E2 and/or HFD are mainly responsible for immune response, inflammatory response and metabolic pathways. Further IPA analysis demonstrated that the acute phase response signaling, NF-κB signaling, leukocyte extravasation signaling, PPAR signaling and LXR/RXR activation pathways are mainly involved in the pathways above. In addition, the genes modulated reciprocally by E2 and/or HFD were also analyzed, and their crosstalk mainly focuses on enhancing one another’s activity. The combination analysis of microarray data and TCGA database provided potential diagnostic or therapeutic targets for EC. Further validation was performed in mice endometrium and human EC cell lines. In conclusion, this study unraveled the endometrial transcriptome profile alterations affected by E2 and/or HFD that may disturb endometrial homeostasis and contribute to the development of endometrial hyperplasia.

  11. Short Course Vaginal Cuff Brachytherapy in Treating Patients With Stage I-II Endometrial Cancer

    Science.gov (United States)

    2018-04-17

    Endometrial Clear Cell Adenocarcinoma; Endometrial Endometrioid Adenocarcinoma; Endometrial Serous Adenocarcinoma; Stage I Uterine Corpus Cancer; Stage IA Uterine Corpus Cancer; Stage IB Uterine Corpus Cancer; Stage II Uterine Corpus Cancer; Uterine Corpus Carcinosarcoma; Uterine Corpus Sarcoma

  12. Accuracy of Endometrial Sampling in Endometrial Carcinoma: A Systematic Review and Meta-analysis.

    Science.gov (United States)

    Visser, Nicole C M; Reijnen, Casper; Massuger, Leon F A G; Nagtegaal, Iris D; Bulten, Johan; Pijnenborg, Johanna M A

    2017-10-01

    To assess the agreement between preoperative endometrial sampling and final diagnosis for tumor grade and subtype in patients with endometrial carcinoma. MEDLINE, EMBASE, ClinicalTrials.gov, and the Cochrane library were searched from inception to January 1, 2017, for studies that compared tumor grade and histologic subtype in preoperative endometrial samples and hysterectomy specimens. In eligible studies, the index test included office endometrial biopsy, hysteroscopic biopsy, or dilatation and curettage; the reference standard was hysterectomy. Outcome measures included tumor grade, histologic subtype, or both. Two independent reviewers assessed the eligibility of the studies. Risk of bias was assessed (Quality Assessment of Diagnostic Accuracy Studies). A total of 45 studies (12,459 patients) met the inclusion criteria. The pooled agreement rate on tumor grade was 0.67 (95% CI 0.60-0.75) and Cohen's κ was 0.45 (95% CI 0.34-0.55). Agreement between hysteroscopic biopsy and final diagnosis was higher (0.89, 95% CI 0.80-0.98) than for dilatation and curettage (0.70, 95% CI 0.60-0.79; P=.02); however, it was not significantly higher than for office endometrial biopsy (0.73, 95% CI 0.60-0.86; P=.08). The lowest agreement rate was found for grade 2 carcinomas (0.61, 95% CI 0.53-0.69). Downgrading was found in 25% and upgrading was found in 21% of the endometrial samples. Agreement on histologic subtypes was 0.95 (95% CI 0.94-0.97) and 0.81 (95% CI 0.69-0.92) for preoperative endometrioid and nonendometrioid carcinomas, respectively. Overall there is only moderate agreement on tumor grade between preoperative endometrial sampling and final diagnosis with the lowest agreement for grade 2 carcinomas.

  13. Are endometrial nerve fibres unique to endometriosis? A prospective case-control study of endometrial biopsy as a diagnostic test for endometriosis in women with pelvic pain.

    Science.gov (United States)

    Ellett, Lenore; Readman, Emma; Newman, Marsali; McIlwaine, Kate; Villegas, Rocio; Jagasia, Nisha; Maher, Peter

    2015-12-01

    endometrial biopsy were 13.6 and 68.2% respectively, positive predictive value was 30.0% and negative predictive value was 44.1%. This was a relatively small sample size and studies like this are subject to the heterogeneous nature of the patient population and tissue samples, despite our best efforts to regulate these parameters. Our results demonstrate that fine nerve fibres are present in women with and without endometriosis. Future work should focus on the function of endometrial nerves and whether these nerves are involved with the subfertility or pain that endometriosis sufferers experience. Our study does not support the detection of endometrial nerve fibres as a non-invasive diagnostic test of endometriosis in women with pelvic pain. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  14. Endometrial carcinoma occuring from polycystic ovary disease : A case report

    International Nuclear Information System (INIS)

    Seong, Su Ok; Jeon, Woo Ki

    1996-01-01

    Endometrial carcinoma usually occurs in postmenopausal women ; less than 5% occurs in women under the age of 40. Up to one quarter of endometrial carcinoma patients below this age have PCO(polycystic ovary disease, Stein-Leventhal syndrome). The increased incidence of endometrial carcinoma in patients with PCO is related to chronic estrogenic stimulation. We report MR imaging in one case of endometrial carcinoma occuring in a 23 year old woman with PCO and had complained of hypermenorrhea for about three years. On T2-weighted MR image the endometrial cavity was seen to be distended with protruded endometrial masses of intermediate signal intensity, and the junctional zone was disrupted beneath the masses. Both ovaries were best seen on T2-weighted MR imaging and showed multiple small peripheral cysts and low signal-intensity central stroma

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

    Science.gov (United States)

    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.

  16. Endometrial carcinoma occuring from polycystic ovary disease : A case report

    Energy Technology Data Exchange (ETDEWEB)

    Seong, Su Ok; Jeon, Woo Ki [Inje Univ. College of Medicine, Seoul (Korea, Republic of)

    1996-12-01

    Endometrial carcinoma usually occurs in postmenopausal women ; less than 5% occurs in women under the age of 40. Up to one quarter of endometrial carcinoma patients below this age have PCO(polycystic ovary disease, Stein-Leventhal syndrome). The increased incidence of endometrial carcinoma in patients with PCO is related to chronic estrogenic stimulation. We report MR imaging in one case of endometrial carcinoma occuring in a 23 year old woman with PCO and had complained of hypermenorrhea for about three years. On T2-weighted MR image the endometrial cavity was seen to be distended with protruded endometrial masses of intermediate signal intensity, and the junctional zone was disrupted beneath the masses. Both ovaries were best seen on T2-weighted MR imaging and showed multiple small peripheral cysts and low signal-intensity central stroma.

  17. Abnormal Uterine Bleeding- evaluation by Endometrial Aspiration.

    Science.gov (United States)

    Singh, Pratibha

    2018-01-01

    Endometrial evaluation is generally indicated in cases presenting with abnormal uterine bleeding (AUB), especially in women more than 35 years of age. AUB encompasses a variety of presentation, for example, heavy menstrual bleeding, frequent bleeding, irregular vaginal bleeding, postcoital and postmenopausal bleeding to name a few. Many methods are used for the evaluation of such cases, with most common being sonography and endometrial biopsy with very few cases requiring more invasive approach like hysteroscopy. Endometrial aspiration is a simple and safe office procedure used for this purpose. We retrospectively analyzed cases of AUB where endometrial aspiration with Pipette (Medgyn) was done in outpatient department between January 2015 and April 2016. Case records (both paper and electronic) were used to retrieve data. One hundred and fifteen cases were included in the study after applying inclusion and exclusion criteria. Most cases were between 46 and 50 years of age followed by 41-45 years. No cases were below 25 or more than 65 years of age. Heavy menstrual bleeding was the most common presentation of AUB. Adequate samples were obtained in 86% of cases while 13.9% of cases' sample was inadequate for opinion, many of which were later underwent hysteroscopy and/or dilatation and curettage (D and C) in operation theater; atrophic endometrium was the most common cause for inadequate sample. Uterine malignancy was diagnosed in three cases. Endometrial aspiration has been compared with traditional D and C as well as postoperative histopathology in various studies with good results. Many such studies are done in India as well as in western countries confirming good correlation with histopathology and adequate tissue sample for the pathologist to give a confident diagnosis. No complication or side effect was noted with the use of this device. Endometrial aspiration is a simple, safe, and effective method to sample endometrium in cases of AUB avoiding risk of

  18. Abnormal Uterine Bleeding- evaluation by Endometrial Aspiration

    Directory of Open Access Journals (Sweden)

    Pratibha Singh

    2018-01-01

    Full Text Available Endometrial evaluation is generally indicated in cases presenting with abnormal uterine bleeding (AUB, especially in women more than 35 years of age. AUB encompasses a variety of presentation, for example, heavy menstrual bleeding, frequent bleeding, irregular vaginal bleeding, postcoital and postmenopausal bleeding to name a few. Many methods are used for the evaluation of such cases, with most common being sonography and endometrial biopsy with very few cases requiring more invasive approach like hysteroscopy. Endometrial aspiration is a simple and safe office procedure used for this purpose. Materials and Methods: We retrospectively analyzed cases of AUB where endometrial aspiration with Pipette (Medgyn was done in outpatient department between January 2015 and April 2016. Case records (both paper and electronic were used to retrieve data. Results: One hundred and fifteen cases were included in the study after applying inclusion and exclusion criteria. Most cases were between 46 and 50 years of age followed by 41–45 years. No cases were below 25 or more than 65 years of age. Heavy menstrual bleeding was the most common presentation of AUB. Adequate samples were obtained in 86% of cases while 13.9% of cases' sample was inadequate for opinion, many of which were later underwent hysteroscopy and/or dilatation and curettage (D and C in operation theater; atrophic endometrium was the most common cause for inadequate sample. Uterine malignancy was diagnosed in three cases. Discussion: Endometrial aspiration has been compared with traditional D and C as well as postoperative histopathology in various studies with good results. Many such studies are done in India as well as in western countries confirming good correlation with histopathology and adequate tissue sample for the pathologist to give a confident diagnosis. No complication or side effect was noted with the use of this device. Conclusion: Endometrial aspiration is a simple, safe, and

  19. PTEN Sequence Analysis in Endometrial Hyperplasia and Endometrial Carcinoma in Slovak Women

    Directory of Open Access Journals (Sweden)

    H. Gbelcová

    2015-01-01

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

  20. Usefulness of MRI in diagnosis of endometrial carcinoma and endometrial hyperplasia

    Energy Technology Data Exchange (ETDEWEB)

    Kasai, Mayumi; Moriai, Kayo; Murai, Shinya; Imai, Toshihiko; Iida, Hajime; Suzuki, Hiroshi (Iwate Prefectural Central Hospital, Morioka (Japan))

    1994-06-01

    The study was to assess the usefulness of T2-weighted and enhanced T1-weighted MR images in differentiating endometrial adenocarcinoma and hyperplasia. The subjects were 21 patients with endometrial hyperplasia (Group A), consisting of 15 with cystic glandular hyperplasia and 6 with atypical hyperplasia, and 7 with endometrial adenocarcinoma (Group B). Six other patients with no evidence of abnormal endometrial findings served as controls. In Group A, the endometrium had a high signal intensity on T2-weighted images, and was 10 mm or over in thickness before menopause and 6 mm after menopause. It was also a high or intermediate signal intensity on enhanced T1-weighted images. In patiemts with cystic glandular hyperplasia, the junctional zone was 10 mm or over on T2-weighted images. Similar findings were seen on enhanced T1-weighted images. In patients with atypical hyperplasia, the junctional zone disappeared or decreased on enhanced images compared with those on T2-weighted images. In group B, the endometrium had an intermediate or high signal intensity on T2-weighted images, with the junctional zone being 10 mm or more. Enhanced T1-weighted images showed lower signal intensities in the tumorous area than in the normal endometrium and muscular layer. These findings indicated that enhanced MR imaging may be useful in diagnosing endometrial lesions. (N.K.).

  1. Effect of Growth Hormone on Endometrial Thickness and Fertility Outcome in the Treatment of Women with Panhypopituitarism: A Case Report.

    Science.gov (United States)

    Drakopoulos, Panagiotis; Pluchino, Nicola; Bischof, Paul; Cantero, Pablo; Meyer, Patrick; Chardonnens, Didier

    2016-01-01

    The role of growth hormone (GH) in female reproduction has become a topic of increasing interest over the last decade. The replacement of GH for ovulation induction in women with hypopituitarism remains controversial. The role of GH in the human endometrium is still largely unknown. To the best of our knowledge, this study represents the first case report showing evidence that GH might play a role not only for ovulation induction, but also for the development of endometrial thickness in women with hypopituitarism. A 32-year-old hypophysectomized. woman, known for primary infertility, experienced multiple IVF/embryo transfer failures with inadequate endometrial development. The use of GH replacement therapy followed by conventional controlled ovarian hyperstimulation enabled endometrial development and better ovarian response to gonadotropins, leading to a successful ongoing pregnancy. The substitution with GH resulted in fewer days of ovarian stimulation, an acceptable endometrium, and a twin pregnancy delivered at 38 weeks' gestation.

  2. Recent Advances in Endometrial Cancer [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Arthur-Quan Tran

    2017-01-01

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

  3. Molecular Biology and Prevention of Endometrial Cancer. Addendum

    National Research Council Canada - National Science Library

    Maxwell, George L

    2008-01-01

    Objective: To increase our understanding of the molecular aberrations associated with endometrial carcinogenesis and the biologic mechanisms underlying the protective effect of oral contraceptive (OC) therapy. Methods: 1...

  4. AN ANALYSIS OF THE POLICY TO PROVIDE THE TRAFFIC INFORMATION IN THE CASE OF EARTHQUAKES AN EXAMPLE ON THE NOTO PENINSULA EARTHQUAKE, ISHIKAWA PREFECTURE

    Science.gov (United States)

    Takahashi, Masanori; Takayama, Jun-Ichi; Nakayama, Shoichiro

    Noto Peninsula earthquake occurred in Ishikawa Pref., in March, 2007, and the Noto Yuryo, and many arterial roads were damaged. This led to the conosiderable confusion of the road traffic in Noto Peninsula area and gave the influence on all kinds of social/economic activities. Therefore, an method of providing the traffic information for drivers is important in the case of disasters such as earthquakes. We carried out a questionnaire survey for local inhabitants and investigated the road use situation at the time of the Noto Peninsula earthquake and the information acquisition situation about it. We also analyzed whether or not the method of providing the traffic information was appropriate. In addition, we examined the best traffic information in the case of earthquakes.

  5. Prognostic factors and treatment of endometrial carcinoma

    International Nuclear Information System (INIS)

    Aalders, J.G.

    1982-01-01

    The aim of the present study was to gain more insight into the natural history of endometrial carcinoma, to evaluate prognostic factors and to assess the various treatment methods and the results. Using the data of the Norwegian Radium Hospital, where treatment of gynecological cancer is centralized to a great extent, a large series of patients with long term follow-up, covering all clinical stages and recurrences of endometrial carcinoma, could be evaluated. This resulted in five articles. These articles, together with a study from the University Hospital in Groningen are presented and discussed, and recommendations for treatment are given. The relevant treatments assessed are postoperative external irradiation, preoperative uterine radium packing, preoperative low dose external irradiation and radiotherapy alone. (Auth.)

  6. Barriers and facilitators to the quality use of essential medicines for maternal health in low-resource countries: An Ishikawa framework.

    Science.gov (United States)

    Tran, Dan N; Bero, Lisa A

    2015-06-01

    An estimated 800 women die every day due to complications related to pregnancy or childbirth. Complications such as postpartum haemorrhage (PPH) and pre-eclampsia and eclampsia can be prevented by the appropriate use of essential medicines. The objective of this study was to identify the common barriers and facilitators to the availability and use of oxytocin, ergometrine, and magnesium sulfate (MgSO4) - essential medicines indicated for the prevention and treatment of PPH and pre-eclampsia and eclampsia. We analyzed seven UNFPA/WHO reports published in 2008-2010. These reports summarized country-wide rapid assessments of access to and use of essential medicines for maternal health in Mongolia, Nepal, Laos, the Democratic People's Republic of Korea (DPRK), the Philippines, Vanuatu, and the Solomon Islands. We used a "fishbone" (Ishikawa) diagram as the analytic framework to identify facilitators and barriers at four health-system levels: government/regulatory, pharmaceutical supply, health facility, and health professional. Common facilitators to the quality use of essential medicines for maternal health were observed at the government/regulatory and health professional level. A majority of countries had these medicines listed in their essential medicines lists. Awareness of the medicines was generally high among health professionals. Common barriers were identified at all health-system levels. First, standard treatment guidelines were not available, updated, or standardized. Second, there was an inadequate capacity to forecast and procure medicines. Third, a required MgSO4 antidote was often not available and the storage conditions for oxytocin were deficient. The "fishbone" Ishikawa diagram is a useful tool for describing the findings of rapid assessments of quality use of essential medicines for maternal health across countries. The facilitators and barriers identified should guide the development of tailored intervention programs to improve and expand the use

  7. Barriers and facilitators to the quality use of essential medicines for maternal health in low–resource countries: An Ishikawa framework

    Directory of Open Access Journals (Sweden)

    Dan N. Tran

    2015-06-01

    Full Text Available Background An estimated 800 women die every day due to complications related to pregnancy or childbirth. Complications such as postpartum haemorrhage (PPH and pre–eclampsia and eclampsia can be prevented by the appropriate use of essential medicines. The objective of this study was to identify the common barriers and facilitators to the availability and use of oxytocin, ergometrine, and magnesium sulfate (MgSO4 – essential medicines indicated for the prevention and treatment of PPH and pre–eclampsia and eclampsia. Methods We analyzed seven UNFPA/WHO reports published in 2008–2010. These reports summarized country–wide rapid assessments of access to and use of essential medicines for maternal health in Mongolia, Nepal, Laos, the Democratic People's Republic of Korea (DPRK, the Philippines, Vanuatu, and the Solomon Islands. We used a “fishbone” (Ishikawa diagram as the analytic framework to identify facilitators and barriers at four health–system levels: government/regulatory, pharmaceutical supply, health facility, and health professional. Results Common facilitators to the quality use of essential medicines for maternal health were observed at the government/regulatory and health professional level. A majority of countries had these medicines listed in their essential medicines lists. Awareness of the medicines was generally high among health professionals. Common barriers were identified at all health–system levels. First, standard treatment guidelines were not available, updated, or standardized. Second, there was an inadequate capacity to forecast and procure medicines. Third, a required MgSO4 antidote was often not available and the storage conditions for oxytocin were deficient. Conclusions The “fishbone” Ishikawa diagram is a useful tool for describing the findings of rapid assessments of quality use of essential medicines for maternal health across countries. The facilitators and barriers identified should guide the

  8. Effect of Radiofrequency Endometrial Ablation on Dysmenorrhea.

    Science.gov (United States)

    Wyatt, Sabrina N; Banahan, Taylor; Tang, Ying; Nadendla, Kavita; Szychowski, Jeff M; Jenkins, Todd R

    To examine rates of dysmenorrhea after radiofrequency endometrial ablation in patients with and without known dysmenorrhea symptoms prior to the procedure in a diverse population. Retrospective cohort study (Canadian Task Force classification II-2). Academic gynecology practice. A total of 307 women underwent endometrial ablation between 2007 and 2013 at our institution. Patients who had preoperative and postoperative pain symptom assessments as well as a description of pain timing recorded were included in our analysis. Exclusion criteria were age dysmenorrhea was evaluated. Demographic information and other outcome variables were used to evaluate factors associated with resolution of dysmenorrhea. A total of 307 patients who underwent radiofrequency endometrial ablation were identified. After exclusions, 296 charts were examined, and 144 patients met our enrollment criteria. The mean age of the study cohort was 45.4 ± 6.2 years; 57 patients (40%) were African American, 16 (11%) had a body mass index (BMI) > 40, and 41 (29%) were of normal weight. Preoperative dysmenorrhea was reported by 100 patients (69%); 48 of these patients (48%) experienced resolution of symptoms postoperatively. Only 3 of the 44 patients (7%) without preoperative dysmenorrhea reported new-onset dysmenorrhea postoperatively. Significantly fewer patients had dysmenorrhea after compared to before radiofrequency ablation (55 of 144 [38%] vs 100 of 144 [69%]; p dysmenorrhea after ablation was associated with reduction in bleeding volume (p = .048) but not with a reduction in frequency of bleeding (p = .12). Approximately one-half of women who undergo radiofrequency endometrial ablation to treat heavy menstrual bleeding who also have preoperative dysmenorrhea exhibit documented pain resolution after the procedure. Resolution of dysmenorrhea is more likely if menstrual flow volume is decreased postprocedure. Copyright © 2016 AAGL. Published by Elsevier Inc. All rights reserved.

  9. An unusual presentation of endometrial polyp

    International Nuclear Information System (INIS)

    Haque, Tabassum Laz; Koyama, Takashi; Konishi, Junji; Togashi, Kaori; Fujii, Shingo

    2002-01-01

    A 33-year-old woman was incidentally found to have a polypoid adenofibroma on MR imaging during the evaluation of carcinoma in situ of the cervix. The position of the polypoid lesion was variable from time to time. Although the lesion was a benign pedunculated one, T2-weighted MR images showed disruption of ''junctional zone'' in the posterior myometrial wall of the uterus, mimicking myometrial invasion of endometrial carcinoma. (orig.)

  10. An unusual presentation of endometrial polyp

    Energy Technology Data Exchange (ETDEWEB)

    Haque, Tabassum Laz; Koyama, Takashi; Konishi, Junji [Department of Nuclear Medicine and Diagnostic Imaging, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto-shi 606-8507 (Japan); Togashi, Kaori [Hitachi Medical Corporation Chair of Department of Diagnostic and Interventional Imageology, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto-shi 606-8507 (Japan); Fujii, Shingo [Department of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto-shi, 606-8507 (Japan)

    2002-12-01

    A 33-year-old woman was incidentally found to have a polypoid adenofibroma on MR imaging during the evaluation of carcinoma in situ of the cervix. The position of the polypoid lesion was variable from time to time. Although the lesion was a benign pedunculated one, T2-weighted MR images showed disruption of ''junctional zone'' in the posterior myometrial wall of the uterus, mimicking myometrial invasion of endometrial carcinoma. (orig.)

  11. Adenomyosis and 'endometrial-subendometrial myometrium unit disruption disease' are two different entities.

    Science.gov (United States)

    Tocci, Angelo; Greco, Ermanno; Ubaldi, Filippo Maria

    2008-08-01

    The diagnosis of adenomyosis is feasible on pathological specimen examination, while it is unreliable on clinical findings, biopsy, hysteroscopy, sonohysterography, and routine ultrasound or magnetic resonance imaging. Several patterns of 'abnormality' described on imaging have been linked to adenomyosis, but the correlation is weak and the diagnostic accuracy is low outside of a research context. Nevertheless, thickening or abnormality of the subendometrial myometrium, the outer part of the 'endometrial-subendometrial myometrium unit' (thought to be important in human fertility) has been repeatedly documented on imaging, called 'adenomyosis' and linked to infertility. This paper discusses the value of the physiological endometrial-subendometrial myometrium unit in human fertility, reviews the current criteria for its imaging, and reports on its relationship to fertility. It is proposed that endometrial-subendometrial myometrium unit disruption disease is considered as a new entity (distinguished from adenomyosis), the diagnosis of which is feasible and straightforward on imaging and expressed mainly by pathological thickening or abnormality of the subendometrial myometrium (myometrial halo or junctional zone). The study also reports on the influence of abnormal thickening or disruption on human fertility and outcome of assisted reproduction techniques, and demonstrates that this new entity is epidemiologically different from adenomyosis.

  12. [The Role of 5-Aza-CdR on Methylation of Promoter in RASSF1A Gene in Endometrial Carcinoma].

    Science.gov (United States)

    Huang, Li-ping; Chen, Chen; Wang, Xue-ping; Liu, Hui

    2015-05-01

    To explore the effect of demethylating drug 5-Aza-2'-deoxycytidine (5-Aza-CdR) on methtylation status of the Ras-association domain familylA gene (RASSF1A) in human endometrial carcinoma. Randomly'assign the human endometrial carcinoma cell line HEC-1-B into groups and use demethylating drug 5-Aza-CdR of different concentration to treat them. Then Methylation-specific polymerase chain reaction (MSP), real-time PCR, Western blot, TUNEL technology were used to analyze methylation status of RASSF1A promoter CpG islands, RASSF1A mRNA expression, RASSF1A protein expression and apoptosis of HEC-1-B cell. High DNA methylation in RASSF1A gene promoter region, low RASSF1A mRNA level and protein expression and out of control of human endometrial carcinoma cell HEC-1-B apoptosis were observed. 5-Aza-CdR of different concentration could reverse RASSF1A gene's methylation status, recover the expression of mRNA and protein, and control the growth of HEC-1-B by inducing apoptosis. Aberrant methylation of RASSF1A in endometrial cancer as a therapeutic target, demethylating agent 5-Aza-CdR could be an effective way of gene therapy.

  13. Sonohysterographic findings of endometrial abnormalities in women with polycystic ovarian disease

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eun Ju [Ajou University School of Medicine, Suwon (Korea, Republic of)

    2004-06-15

    To describe the sonohysterographic findings of endometrial abnormalities, and to determine the usefulness of sonohysterography (SH) for predicting endometrial abnormalities in women with polycystic ovarian disease(PCOD). 82 patients with PCOD who had vaginal bleeding or endometrial thickening and lesion mass on baseline transvaginal sonography were prospectively examined with SH. The SH findings were evaluated for endometrial thickness, the presence of endometrial thickening and lesion mass, echogenicity and surface contour, distensibility of the endometrial cavity, and disruption of endometrial-myometrial interface. These findings were compared with the pathologic findings and the diagnostic accuracy of SH for predicting endometrial abnormalities was assessed. Endometrial abnormalities were identified in 47 (57.3%) of 82 PCOD patients, and their pathologic diagnosis included endometrial carcinoma in 7 cases, hyperplasia in 19 cases (atypical hyperplasia, n=5), and polyp in 21 cases. Of the 35 patients who did not have endometrial abnormalities, there was disordered proliferative endometrium in 18 cases and normal proliferative or secretory endometrium in 17 cases. The SH findings of endometrial carcinoma were endometrial thickening in 5 cases, endometrial thickening and lesion mass in 2 cases, and the endometrial thickness ranged from 6 mm to 15 mm (mean 9.5 mm). They were characterized as a diffuse polyploid endometrial thickening or a sessile endometrial mass with irregular surface, homogeneous hyperechogenicity, and obliteration of the endometrial cavity. Endometrial hyperplasia appeared as endometrial thickening in 14 cases, endometrial lesion mass in 3 cases, and endometrial thickening and lesion mass in 2 cases, and the endometrial thickness was between 6.5-10.7 mm (mean 8.2 mm). They showed a diffuse uniform endometrial thickening or a polyploid endometrial lesion mass with homogeneous hyperechogenicity and a regular surface. Endometrial polyps appeared as

  14. Sonohysterographic findings of endometrial abnormalities in women with polycystic ovarian disease

    International Nuclear Information System (INIS)

    Lee, Eun Ju

    2004-01-01

    To describe the sonohysterographic findings of endometrial abnormalities, and to determine the usefulness of sonohysterography (SH) for predicting endometrial abnormalities in women with polycystic ovarian disease(PCOD). 82 patients with PCOD who had vaginal bleeding or endometrial thickening and lesion mass on baseline transvaginal sonography were prospectively examined with SH. The SH findings were evaluated for endometrial thickness, the presence of endometrial thickening and lesion mass, echogenicity and surface contour, distensibility of the endometrial cavity, and disruption of endometrial-myometrial interface. These findings were compared with the pathologic findings and the diagnostic accuracy of SH for predicting endometrial abnormalities was assessed. Endometrial abnormalities were identified in 47 (57.3%) of 82 PCOD patients, and their pathologic diagnosis included endometrial carcinoma in 7 cases, hyperplasia in 19 cases (atypical hyperplasia, n=5), and polyp in 21 cases. Of the 35 patients who did not have endometrial abnormalities, there was disordered proliferative endometrium in 18 cases and normal proliferative or secretory endometrium in 17 cases. The SH findings of endometrial carcinoma were endometrial thickening in 5 cases, endometrial thickening and lesion mass in 2 cases, and the endometrial thickness ranged from 6 mm to 15 mm (mean 9.5 mm). They were characterized as a diffuse polyploid endometrial thickening or a sessile endometrial mass with irregular surface, homogeneous hyperechogenicity, and obliteration of the endometrial cavity. Endometrial hyperplasia appeared as endometrial thickening in 14 cases, endometrial lesion mass in 3 cases, and endometrial thickening and lesion mass in 2 cases, and the endometrial thickness was between 6.5-10.7 mm (mean 8.2 mm). They showed a diffuse uniform endometrial thickening or a polyploid endometrial lesion mass with homogeneous hyperechogenicity and a regular surface. Endometrial polyps appeared as

  15. Uterine endometrial stromal sarcoma located in uterine myometrium: MRI appearance

    Energy Technology Data Exchange (ETDEWEB)

    Ueda, M.; Otsuka, M.; Hatakenaka, M. [Dept. of Radiology, Medical Institute of Bioregulation, Kyushu University, Beppu (Japan); Torii, Y. [Dept. of Radiology, Saga Prefectural Hospital (Japan)

    2000-05-01

    Two cases of uterine endometrial stromal sarcoma whose main mass was located in uterine myometrium are reported. They mimicked uterine leiomyoma with cystic degeneration or uterine leiomyosarcoma. Endometrial stromal sarcoma should be suggested in the differential diagnosis of mass lesion in uterine myometrium. (orig.)

  16. Endometrial safety of ultra-low-dose estradiol vaginal tablets

    DEFF Research Database (Denmark)

    Simon, James; Nachtigall, Lila; Ulrich, Lian G

    2010-01-01

    To evaluate the endometrial hyperplasia and carcinoma rate after 52-week treatment with ultra-low-dose 10-microgram 17ß-estradiol vaginal tablets in postmenopausal women with vaginal atrophy.......To evaluate the endometrial hyperplasia and carcinoma rate after 52-week treatment with ultra-low-dose 10-microgram 17ß-estradiol vaginal tablets in postmenopausal women with vaginal atrophy....

  17. Endometrial safety of ultra-low-dose estradiol vaginal tablets

    DEFF Research Database (Denmark)

    Simon, James; Nachtigall, Lila; Ulrich, Lian G

    2010-01-01

    To evaluate the endometrial hyperplasia and carcinoma rate after 52-week treatment with ultra-low-dose 10-microgram 17β-estradiol vaginal tablets in postmenopausal women with vaginal atrophy.......To evaluate the endometrial hyperplasia and carcinoma rate after 52-week treatment with ultra-low-dose 10-microgram 17β-estradiol vaginal tablets in postmenopausal women with vaginal atrophy....

  18. Endometrial sampling in infertility: the Ilorin, Nigeria, experience ...

    African Journals Online (AJOL)

    The aim of this study is to determine the diagnosis value of endometrium sampling in detecting endometrial pathology and presence or absence of ovulation in infertility patients. A retrospective study of endometrial tissues histopathological slides of infertility patients as recorded in the register of the department of Pathology, ...

  19. Endometrial Osseous Metaplasia: Case Report with Literature Review

    African Journals Online (AJOL)

    Endometrial osseous metaplasia is a rare entity[1] and Nearly. 80 cases have been reported in the world literature including, nine from India[2] and it is the presence of mature or immature bone in the endometrium.[1] Osseous metaplasia of the endometrium has also been incorrectly named as endometrial ossification ...

  20. Endometrial pathology in a teaching hospital in North Central ...

    African Journals Online (AJOL)

    The study was a 5 year histopathological survey of endometrial biopsies seen at the University of Ilorin Teaching Hospital , Ilorin, North Central Nigeria from January 1st 1997 to December 31st 2001. It aimed at identifying the morphological patterns of endometrial disorders, prevalence of these disorders and the ...

  1. Histological changes in the endometrial of pregnant Sprague ...

    African Journals Online (AJOL)

    This study describes a changed uterine morphometry and its application to the endometrial structure of a pregnant rat. The number and the size of uterine gland and blood vessels changed during the pregnancy period of the rat. This effect on day 15 was significantly changed in the different groups. When the endometrial ...

  2. An endometrial histomorphometric study of CD56 + natural killer ...

    African Journals Online (AJOL)

    Background. The number of peripheral blood and endometrial natural killer cells varies greatly during implantation and the first trimester of pregnancy and is thought to play a role in the maintenance of a healthy pregnancy. However, the role of endometrial CD56+ natural killer (NK) cells as an immunological mechanism in ...

  3. A 2-decade review of histopathological pattern of endometrial ...

    African Journals Online (AJOL)

    Background: Endometrial biopsy is a commonly performed procedure with a wide range of possible histopathological diagnoses. Objective: To determine the clinical spectrum, frequency and age distribution of endometrial pathologies at the University of Maiduguri Teaching Hospital (UMTH), Maiduguri. Methods: This was a ...

  4. Effect of parity on endometrial glands in gravid rabbits | Pulei ...

    African Journals Online (AJOL)

    Effect of parity on endometrial glands in gravid rabbits. ... Anatomy Journal of Africa ... Image J. Endometrial gland density was noted to decrease with a rise in parity such that the percentage proportion in the primigravid rabbit was 45% compared to that of 34% and 37.5% in the biparous and multiparous groups respectively.

  5. Biochemical evaluation of endometrial function at the time of implantation

    DEFF Research Database (Denmark)

    Lindhard, Anette; Bentin-Ley, Ursula; Ravn, Vibeke

    2002-01-01

    OBJECTIVE: To review the literature on various endometrial factors assumed to be of importance to implantation and to evaluate their potential clinical value in the assessment of endometrial function at the time of implantation in infertile women in natural and stimulated cycles. DESIGN: Literatu...

  6. Pregnancy loss: a rare consequence of premenstrual endometrial ...

    African Journals Online (AJOL)

    Two cases of pregnancy loss - a rare complication of pre-menstrual endometrial biopsy (PMEB) are reported. PMEB is an investigation performed for infertile women to assess ovulation and endometrial factors. It is usually performed during the secretory phase of the cycle. This implies that ovulation and possibly fertilization ...

  7. Hypoxia and cell cycle deregulation in endometrial carcinogenesis

    NARCIS (Netherlands)

    Horrée, N.

    2007-01-01

    Because uterine endometrial carcinoma is the most common malignancy of the female genital tract and 1 of every 5 patients dies of this disease, understanding the mechanisms of carcinogenesis and progression of endometrial carcinoma is important. In general, this thesis can be summarized as a study

  8. Association of microRNA-200c expression levels with clinicopathological factors and prognosis in endometrioid endometrial cancer.

    Science.gov (United States)

    Wilczynski, Milosz; Danielska, Justyna; Domanska-Senderowska, Daria; Dzieniecka, Monika; Szymanska, Bozena; Malinowski, Andrzej

    2018-05-01

    MicroRNAs (miRNAs) are regulators of gene expression, which play an important role in many critical cellular processes including apoptosis, proliferation and cell differentiation. Aberrant miRNA expression has been reported in a variety of human malignancies. Therefore, miRNAs may be potentially used as cancer biomarkers. miRNA-200c, which is a member of the miRNA-200 family, might play an essential role in tumor progression. The purpose of this study was to evaluate the prognostic and clinical significance of miRNA-200c in women with endometrioid endometrial cancer. Total RNA extraction from 90 archival formalin-fixed paraffin-embedded tissue samples of endometri-oid endometrial cancer and 10 normal endometrium samples was performed. After cDNA synthesis, real-time polymerase chain reaction was conducted and relative expression of miRNA-200c was assessed. Then, miRNA-200c expression levels were evaluated with regard to clinicopathological characteristics. The expression levels of miRNA-200c were significantly increased in endometrioid endometrial cancer samples. Expression of miRNA-200c maintained at significantly higher levels in the early stage endometrioid endometrial cancer compared with more advanced stages. In the Kaplan-Meier analysis, lower levels of miRNA-200c expression were associated with inferior survival. Expression levels of miRNA-200c might be associated with clinicopathological factors and survival in endometrioid endometrial cancer. © 2018 Nordic Federation of Societies of Obstetrics and Gynecology.

  9. [Establishment of mouse endometrial injury model by electrocoagulation].

    Science.gov (United States)

    Hu, Xiaoxiao; Lin, Xiaona; Jiang, Yinshen; Shi, Libing; Wang, Jieyu; Zhao, Lijuan; Zhang, Songying

    2014-12-23

    To establish the murine model of moderate endometrial injury. Electrocoagulation was applied to induce endometrial injury of ICR mice with 0.5 watts power while contralateral uterine cavity acted as control without electrocoagulation. The endometrial histomorphology was observed in 7 days later by microscopy and fetal number of each lateral uterus assessed at 17.5 days after pregnancy. At 7 days post-electrocoagulation, the average endometrial thickness of operating side was significantly thinner than that of control side (1.14 ± 0.08 vs 1.88 ± 0.15 mm, P electrocoagulation injury shows morphologic changes and decreased fertile ability. It has potential uses for animal studies of endometrial injury treatment.

  10. Leiomyoma-derived transforming growth factor-β impairs bone morphogenetic protein-2-mediated endometrial receptivity.

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    Doherty, Leo F; Taylor, Hugh S

    2015-03-01

    To determine whether transforming growth factor (TGF)-β3 is a paracrine signal secreted by leiomyoma that inhibits bone morphogenetic protein (BMP)-mediated endometrial receptivity and decidualization. Experimental. Laboratory. Women with symptomatic leiomyomas. Endometrial stromal cells (ESCs) and leiomyoma cells were isolated from surgical specimens. Leiomyoma-conditioned media (LCM) was applied to cultured ESC. The TGF-β was blocked by two approaches: TGF-β pan-specific antibody or transfection with a mutant TGF-β receptor type II. Cells were then treated with recombinant human BMP-2 to assess BMP responsiveness. Expression of BMP receptor types 1A, 1B, 2, as well as endometrial receptivity mediators HOXA10 and leukemia inhibitory factor (LIF). Enzyme-linked immunosorbent assay showed elevated TGF-β levels in LCM. LCM treatment of ESC reduced expression of BMP receptor types 1B and 2 to approximately 60% of pretreatment levels. Preincubation of LCM with TGF-β neutralizing antibody or mutant TGF receptor, but not respective controls, prevented repression of BMP receptors. HOXA10 and LIF expression was repressed in recombinant human BMP-2 treated, LCM exposed ESC. Pretreatment of LCM with TGF-β antibody or transfection with mutant TGF receptor prevented HOXA10 and LIF repression. Leiomyoma-derived TGF-β was necessary and sufficient to alter endometrial BMP-2 responsiveness. Blockade of TGF-β prevents repression of BMP-2 receptors and restores BMP-2-stimulated expression of HOXA10 and LIF. Blockade of TGF signaling is a potential strategy to improve infertility and pregnancy loss associated with uterine leiomyoma. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  11. Acceleration of the glycolytic flux by steroid receptor coactivator-2 is essential for endometrial decidualization.

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    Ramakrishna Kommagani

    2013-10-01

    Full Text Available Early embryo miscarriage is linked to inadequate endometrial decidualization, a cellular transformation process that enables deep blastocyst invasion into the maternal compartment. Although much of the cellular events that underpin endometrial stromal cell (ESC decidualization are well recognized, the individual gene(s and molecular pathways that drive the initiation and progression of this process remain elusive. Using a genetic mouse model and a primary human ESC culture model, we demonstrate that steroid receptor coactivator-2 (SRC-2 is indispensable for rapid steroid hormone-dependent proliferation of ESCs, a critical cell-division step which precedes ESC terminal differentiation into decidual cells. We reveal that SRC-2 is required for increasing the glycolytic flux in human ESCs, which enables rapid proliferation to occur during the early stages of the decidualization program. Specifically, SRC-2 increases the glycolytic flux through induction of 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 3 (PFKFB3, a major rate-limiting glycolytic enzyme. Similarly, acute treatment of mice with a small molecule inhibitor of PFKFB3 significantly suppressed the ability of these animals to exhibit an endometrial decidual response. Together, these data strongly support a conserved mechanism of action by which SRC-2 accelerates the glycolytic flux through PFKFB3 induction to provide the necessary bioenergy and biomass to meet the demands of a high proliferation rate observed in ESCs prior to their differentiation into decidual cells. Because deregulation of endometrial SRC-2 expression has been associated with common gynecological disorders of reproductive-age women, this signaling pathway, involving SRC-2 and PFKFB3, promises to offer new clinical approaches in the diagnosis and/or treatment of a non-receptive uterus in patients presenting idiopathic infertility, recurrent early pregnancy loss, or increased time to pregnancy.

  12. Molecular changes preceding endometrial and ovarian cancer: a study of consecutive endometrial specimens from Lynch syndrome surveillance.

    Science.gov (United States)

    Niskakoski, Anni; Pasanen, Annukka; Lassus, Heini; Renkonen-Sinisalo, Laura; Kaur, Sippy; Mecklin, Jukka-Pekka; Bützow, Ralf; Peltomäki, Päivi

    2018-03-27

    Molecular alterations preceding endometrial and ovarian cancer and the sequence of events are unknown. Consecutive specimens from lifelong surveillance for Lynch syndrome provides a natural setting to address such questions. To molecularly define the multistep gynecological tumorigenesis, DNA mismatch repair gene mutation carriers with endometrial or ovarian carcinoma or endometrial hyperplasia were identified from a nation-wide registry and endometrial biopsy specimens taken from these individuals during 20 years of screening were collected. A total of 213 endometrial and ovarian specimens from Lynch syndrome individuals and 197 histology-matched (non-serous) samples from sporadic cases were available for this investigation. The specimens were profiled for markers linked to endometrial and ovarian tumorigenesis, including ARID1A protein expression, mismatch repair status, and tumor suppressor gene promoter methylation. In Lynch syndrome-associated endometrial and ovarian carcinomas, ARID1A protein was lost in 61-100% and mismatch repair was deficient in 97-100%, compared to 0-17% and 14-44% in sporadic cases (P = 0.000). ARID1A loss appeared in complex hyperplasia and deficient mismatch repair and tumor suppressor gene promoter methylation in histologically normal endometrium. Despite quantitative differences between Lynch syndrome and sporadic cases, ARID1A expression, mismatch repair, and tumor suppressor gene promoter methylation divided endometrial samples from both patient groups into three categories of increasing abnormality, comprising normal endometrium and simple hyperplasia (I), complex hyperplasia with or without atypia (II), and endometrial cancer (III). Complex hyperplasias without vs. with atypia were molecularly indistinguishable. In conclusion, surveillance specimens from Lynch syndrome identify mismatch repair deficiency, tumor suppressor gene promoter methylation, and ARID1A loss as early changes in tumor development. Our findings are

  13. Feasibility investigation of allogeneic endometrial regenerative cells

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    Reid Michael

    2009-02-01

    Full Text Available Abstract Endometrial Regenerative Cells (ERC are a population of mesenchymal-like stem cells having pluripotent differentiation activity and ability to induce neoangiogenesis. In vitro and animal studies suggest ERC are immune privileged and in certain situations actively suppress ongoing immune responses. In this paper we describe the production of clinical grade ERC and initial safety experiences in 4 patients with multiple sclerosis treated intravenously and intrathecally. The case with the longest follow up, of more than one year, revealed no immunological reactions or treatment associated adverse effects. These preliminary data suggest feasibility of clinical ERC administration and support further studies with this novel stem cell type.

  14. Clinical significance of inadequate endometrial biopsies prior to hysterectomy.

    Science.gov (United States)

    Turney, Emily H; Farghaly, Hanan; Eskew, Ashley M; Parker, Lynn P; Milam, Michael R

    2012-01-01

    To evaluate preoperative clinical risk factors associated with significant uterine histopathologic abnormalities in final hysterectomy specimens in patients with inadequate preoperative endometrial biopsies. This is an institutional review board-approved, retrospective cohort analysis of 469 consecutive patients who underwent preoperative endometrial biopsies with subsequent hysterectomy from January 1, 2005, to December 31, 2009, at the University of Louisville Medical Center. We analyzed risk factors for inadequate biopsy and for final diagnosis of endometrial pathology (defined as endometrial hyperplasia or uterine cancer). Of the 469 preoperative endometrial biopsies reviewed, 26.2% (123/469) were inadequate (IBx) and 73.8% (346/469) were adequate and benign. IBx on endometrial biopsies was associated with a greater risk of having significant uterine histopathologic abnormalities on final hysterectomy specimens (6.5% vs. 2.3%, RR 2.8 [95% CI 1.1-7.3], p = 0.04). Although inadequate endometrial biopsies are a common finding, they can be associated with significant uterine histopathologic abnormalities on final hysterectomy specimens.

  15. Outpatient endometrial aspiration: an alternative to methotrexate for pregnancy of unknown location.

    Science.gov (United States)

    Insogna, Iris G; Farland, Leslie V; Missmer, Stacey A; Ginsburg, Elizabeth S; Brady, Paula C

    2017-08-01

    Pregnancies of unknown location with abnormal beta-human chorionic gonadotropin trends are frequently treated as presumed ectopic pregnancies with methotrexate. Preliminary data suggest that outpatient endometrial aspiration may be an effective tool to diagnose pregnancy location, while also sparing women exposure to methotrexate. The purpose of this study was to evaluate the utility of an endometrial sampling protocol for the diagnosis of pregnancies of unknown location after in vitro fertilization. A retrospective cohort study of 14,505 autologous fresh and frozen in vitro fertilization cycles from October 2007 to September 2015 was performed; 110 patients were diagnosed with pregnancy of unknown location, defined as a positive beta-human chorionic gonadotropin without ultrasound evidence of intrauterine or ectopic pregnancy and an abnormal beta-human chorionic gonadotropin trend (location, failed intrauterine pregnancy was diagnosed in 46 patients (42%), and ectopic pregnancy was diagnosed in 64 patients (58%). Clinical variables that included fresh or frozen embryo transfer, day of embryo transfer, serum beta-human chorionic gonadotropin at the time of sampling, endometrial thickness, and presence of an adnexal mass were not significantly different between patients with failed intrauterine pregnancy or ectopic pregnancy. In patients with failed intrauterine pregnancy, 100% demonstrated adequate postsampling beta-human chorionic gonadotropin declines; villi were identified in just 46% (n=21 patients). Patients with failed intrauterine pregnancy had significantly shorter time to resolution (negative serum beta-human chorionic gonadotropin) after sampling compared with patients with ectopic pregnancy (12.6 vs 26.3 days; Plocation are spared methotrexate, with a shorter time to pregnancy resolution than those who receive methotrexate. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Trop-2 protein overexpression is an independent marker for predicting disease recurrence in endometrioid endometrial carcinoma

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    Bignotti Eliana

    2012-11-01

    Full Text Available Abstract Background Endometrial cancer is the most common gynecologic malignancy in developed countries. Trop-2 is a glycoprotein involved in cellular signal transduction and is differentially overexpressed relative to normal tissue in a variety of human adenocarcinomas, including endometrioid endometrial carcinomas (EEC. Trop-2 overexpression has been proposed as a marker for biologically aggressive tumor phenotypes. Methods Trop-2 protein expression was quantified using tissue microarrays consisting of formalin-fixed paraffin-embedded specimens from 118 patients who underwent surgical staging from 2001–9 by laparotomy for EEC. Clinicopathologic characteristics including age, stage, grade, lymphovascular space invasion, and medical comorbidities were correlated with immunostaining score. Univariate and multivariate analyses were performed for overall survival, disease-free survival, and progression-free survival in relation to clinical parameters and Trop-2 protein expression. Results Clinical outcome data were available for 103 patients. Strong Trop-2 immunostaining was significantly associated with higher tumor grade (p=0.02 and cervical involvement (p Conclusions Trop-2 protein overexpression is significantly associated with higher tumor grade and serves as an independent prognostic factor for DFS in endometrioid endometrial cancer.

  17. RNA-seq Reveals the Overexpression of IGSF9 in Endometrial Cancer

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    Zonggao Shi

    2018-01-01

    Full Text Available We performed RNA-seq on an Illumina platform for 7 patients with endometrioid endometrial carcinoma for which both tumor tissue and adjacent noncancer tissue were available. A total of 66 genes were differentially expressed with significance level at adjusted p value < 0.01. Using the gene functional classification tool in the NIH DAVID bioinformatics resource, 5 genes were found to be the only enriched group out of that list of genes. The gene IGSF9 was chosen for further characterization with immunohistochemical staining of a larger cohort of human endometrioid carcinoma tissues. The expression level of IGSF9 in cancer cells was significantly higher than that in control glandular cells in paired tissue samples from the same patients (p=0.008 or in overall comparison between cancer and the control (p=0.003. IGSF9 expression is higher in patients with myometrium invasion relative to those without invasion (p=0.015. Reanalysis of RNA-seq dataset from The Cancer Genome Atlas shows higher expression of IGSF9 in endometrial cancer versus normal control and expression was associated with poor prognosis. These results suggest IGSF9 as a new biomarker in endometrial cancer and warrant further studies on its function, mechanism of action, and potential clinical utility.

  18. BAG3 Protein Is Over-Expressed in Endometrioid Endometrial Adenocarcinomas.

    Science.gov (United States)

    Esposito, Veronica; Baldi, Carlo; Zeppa, Pio; Festa, Michelina; Guerriero, Luana; d'Avenia, Morena; Chetta, Massimiliano; Zullo, Fulvio; De Laurenzi, Vincenzo; Turco, Maria Caterina; Rosati, Alessandra; Guida, Maurizio

    2017-02-01

    Endometrioid endometrial cancer is the most common gynaecological tumor in developed countries, and its incidence is increasing. The definition of subtypes, based on clinical and endocrine features or on histopathological characteristics, correlate to some extent with patient's prognosis, but there is substantial heterogeneity within tumor types. The search for molecules and mechanisms implied in determining the progression and the response to therapy for this cancer is still ongoing. BAG3 protein, a member of BAG family of co-chaperones, has a pro-survival role in several tumor types. BAG3 anti-apoptotic properties rely on its characteristic to bind several intracellular partners, thereby, modulating crucial events such as apoptosis, differentiation, cell motility, and autophagy. BAG3 expression in human endometrial cancer tissues was not investigated so far. Here, we show that BAG3 protein levels are elevated in tumoral and hyperplastic cells in respect to normal glands. Furthermore, BAG3 subcellular localization appears to be changed in tumoral compared to normal cells. Our results indicate a possible role for BAG3 protein in the maintenance of cell survival in endometrioid endometrial cancer and suggest that this field of studies is worthy of further investigations. J. Cell. Physiol. 232: 309-311, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  19. Integrins beta 5, beta 3 and alpha v are apically distributed in endometrial epithelium.

    Science.gov (United States)

    Aplin, J D; Spanswick, C; Behzad, F; Kimber, S J; Vićovac, L

    1996-07-01

    Several adhesion molecules have been shown to occur at the surface of endometrial cells. One of these is the integrin alpha v subunit which associates with various beta chains including beta 5. We demonstrate the presence of integrin beta 5 polypeptide in human endometrial epithelial cells throughout the menstrual cycle using immunocytochemistry with monospecific antibodies, and at the mRNA level by thermal amplification from endometrial cDNA. Integrin beta 5 is also found in a population of bone marrow-derived cells. A notable feature of the distribution of the beta 5 subunit in the glandular and luminal epithelium is its apical localization, which may suggest an involvement in implantation. However, no evidence was found for regulated expression of epithelial beta 5. In mouse, the beta 5 subunit is found at both the apical and basal surface of epithelial cells and expression is essentially oestrous cycle-independent. Comparisons are made in both species with the distribution of the alpha v and beta 3 subunits which also localize to the apical epithelium.

  20. Seminal plasma induces global transcriptomic changes associated with cell migration, proliferation and viability in endometrial epithelial cells and stromal fibroblasts

    OpenAIRE

    Chen, Joseph C.; Johnson, Brittni A.; Erikson, David W.; Piltonen, Terhi T.; Barragan, Fatima; Chu, Simon; Kohgadai, Nargis; Irwin, Juan C.; Greene, Warner C.; Giudice, Linda C.; Roan, Nadia R.

    2014-01-01

    STUDY QUESTION How does seminal plasma (SP) affect the transcriptome of human primary endometrial epithelial cells (eEC) and stromal fibroblasts (eSF)? SUMMARY ANSWER Exposure of eEC and eSF to SP in vitro increases expression of genes and secreted proteins associated with cellular migration, proliferation, viability and inhibition of cell death. WHAT IS KNOWN ALREADY Studies in both humans and animals suggest that SP can access and induce physiological changes in the upper female reproductiv...

  1. Development of a new comprehensive and reliable endometrial receptivity map (ER Map/ER Grade) based on RT-qPCR gene expression analysis.

    Science.gov (United States)

    Enciso, M; Carrascosa, J P; Sarasa, J; Martínez-Ortiz, P A; Munné, S; Horcajadas, J A; Aizpurua, J

    2018-02-01

    Is it possible to determine the receptivity status of an endometrium by combined quantitative reverse transcription PCR (RT-qPCR) expression analysis of genes involved in endometrial proliferation and immunity? The new ER Map®/ER Grade® test can predict endometrial receptivity status by RT-qPCR using a new panel of genes involved in endometrial proliferation and the maternal immune response associated to embryonic implantation. The human endometrium reaches a receptive status adequate for embryonic implantation around Days 19-21 of the menstrual cycle. During this period, known as the window of implantation (WOI), the endometrium shows a specific gene expression profile suitable for endometrial function evaluation. The number of molecular diagnostic tools currently available to characterize this process is very limited. In this study, a new system for human endometrial receptivity evaluation was optimized and presented for the first time. ER Map®/ER Grade® validation was achieved on 312 endometrial samples including fertile women and patients undergoing fertility treatment between July 2014 and March 2016. Expression analyses of 184 genes involved in endometrial receptivity and immune response were performed. Samples were additionally tested with an independent endometrial receptivity test. A total of 96 fertile women and 120 assisted reproduction treatment (ART) patients participated in the study. Endometrial biopsy samples were obtained at LH + 2 and LH + 7 days in fertile subjects in a natural cycle and at the window of implantation (WOI) in patients in a hormone-replacement therapy (HRT) cycle. Total RNA was purified, quality-checked and reverse-transcribed. Gene expression was quantified by high-throughput RT-qPCR and statistically analyzed. Informative genes were selected and used to classify samples into four different groups of endometrial receptivity status. Significantly different gene expression levels were found in 85 out of 184 selected genes when

  2. Hypoxia and Angiogenesis in Endometrioid Endometrial Carcinogenesis

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    Nicole Horrée

    2007-01-01

    Full Text Available Background: Hypoxia-inducible factor 1α (HIF-1α plays an essential role in the adaptive response of cells to hypoxia, triggering biologic events associated with aggressive tumor behavior. Methods: Expression of HIF-1α and proteins in the HIF-1α pathway (Glut-1, CAIX, VEGF in paraffin-embedded specimens of normal (n = 17, premalignant (n = 17 and endometrioid endometrial carcinoma (n = 39 was explored by immunohistochemistry, in relation to microvessel density (MVD. Results: HIF-1α overexpression was absent in inactive endometrium but present in hyperplasia (61% and carcinoma (87%, with increasing expression in a perinecrotic fashion pointing to underlying hypoxia. No membranous expression of Glut-1 and CAIX was noticed in inactive endometrium, in contrast with expression in hyperplasia (Glut-1 0%, CAIX 61%, only focal and diffuse and carcinoma (Glut-1 94.6%, CAIX 92%, both mostly perinecrotically. Diffuse HIF-1α was accompanied by activation of downstream targets. VEGF was significantly higher expressed in hyperplasias and carcinomas compared to inactive endometrium. MVD was higher in hyperplasias and carcinomas than in normal endometrium (p < 0.001. Conclusion: HIF-1α and its downstream genes are increasingly expressed from normal through premalignant to endometrioid adenocarcinoma of the endometrium, paralleled by activation of its downstream genes and increased angiogenesis. This underlines the potential importance of hypoxia and its key regulator HIF-1α in endometrial carcinogenesis.

  3. Endometrial hyperplasia in hysteroscopy, Report of 363 cases of hysteroscopy

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    Aghahosseyni M

    1998-05-01

    Full Text Available Hysteroscopy is a new and precise method for evaluating of uterus, so it is valuable in evaluating infertile women. In 18 months, 363 hysteroscopies were done on patients who were visited in IVF center of Shariati Hospital for treatment of infertility. Incidence of abnormal hysteroscopy was 18%. 32% of these abnormal hysteroscopies was endometrial hyperplasia. In evaluating of laparoscopy and other factors of these patients there was a statistically significant relation between diagnosis of PCOD (polycystic ovary disease and endometrial hyperplasia (P<0.008, but there is no significant relation between other diagnoses like endometriosis and endometrial hyperplasia (P<0.4.

  4. Comparative analysis between endometrial proteomes of pregnant and non-pregnant ewes during the peri-implantation period.

    Science.gov (United States)

    Zhao, Haichao; Sui, Linlin; Miao, Kai; An, Lei; Wang, Dong; Hou, Zhuocheng; Wang, Rui; Guo, Min; Wang, Zhilong; Xu, Jiqiang; Wu, Zhonghong; Tian, Jianhui

    2015-01-01

    Early pregnancy failure has a profound impact on both human reproductive health and animal production. 2/3 pregnancy failures occur during the peri-implantation period; however, the underlying mechanism(s) remains unclear. Well-organized modification of the endometrium to a receptive state is critical to establish pregnancy. Aberrant endometrial modification during implantation is thought to be largely responsible for early pregnancy loss. In this study, using well-managed recipient ewes that received embryo transfer as model, we compared the endometrial proteome between pregnant and non-pregnant ewes during implantation period. After embryo transfer, recipients were assigned as pregnant or non-pregnant ewes according to the presence or absence of an elongated conceptus at Day 17 of pregnancy. By comparing the endometrial proteomic profiles between pregnant and non-pregnant ewes, we identified 94 and 257 differentially expressed proteins (DEPs) in the endometrial caruncular and intercaruncular areas, respectively. Functional analysis showed that the DEPs were mainly associated with immune response, nutrient transport and utilization, as well as proteasome-mediated proteolysis. These analysis imply that dysfunction of these biological processes or pathways of DEP in the endometrium is highly associated with early pregnancy loss. In addition, many proteins that are essential for the establishment of pregnancy showed dysregulation in the endometrium of non-pregnant ewes. These proteins, as potential candidates, may contribute to early pregnancy loss.

  5. Current surgical treatment option, utilizing robot-assisted laparoscopic surgery in obese women with endometrial cancer: Farghalys technique

    International Nuclear Information System (INIS)

    Farghaly, S.A.

    2013-01-01

    Background: Endometrial cancer is the most prevalent cancer of the female genital tract in North America. Minimally invasive laparoscopic-assisted surgery and panniculectomy in obese women with endometrial cancer are associated with an improved lymph node count, and lower rate of incisional complications than laparotomy. Methods: Technique for robot-assisted laparoscopic surgery for obese women with endometrial cancer is detailed. Results: Robot-assisted laparoscopic surgical staging, pelvic and para-aortic lymphadenectomy and panniculectomy allow us to avoid the use of postoperative pelvic radiation which is recommended in women with histopathology high-risk findings: deep myometrial invasion or high grade histology. The procedure has the advantage of three-dimensional vision, ergonomic, intuitive control, and wristed instrument that approximate the motion of the human hand. Conclusion: Robot-assisted laparoscopic surgical staging, and panniculectomy in these patients are a safe, and effective alternative to laparoscopic, and laparotomy surgery. It is an ideal tool for performing the complex oncologic procedures encountered in endometrial cancer staging that requires delicate retroperitoneal, pelvic and para-aortic lymph node dissection, while maintaining the principles of oncologic surgery but in a minimally invasive fashion.

  6. Decidualization and syndecan-1 knock down sensitize endometrial stromal cells to apoptosis induced by embryonic stimuli.

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    Sarah Jean Boeddeker

    Full Text Available Human embryo invasion and implantation into the inner wall of the maternal uterus, the endometrium, is the pivotal process for a successful pregnancy. Whereas disruption of the endometrial epithelial layer was already correlated with the programmed cell death, the role of apoptosis of the subjacent endometrial stromal cells during implantation is indistinct. The aim was to clarify whether apoptosis plays a role in the stromal invasion and to characterize if the apoptotic susceptibility of endometrial stromal cells to embryonic stimuli is influenced by decidualization and Syndecan-1. Therefore, the immortalized human endometrial stromal cell line St-T1 was used to first generate a new cell line with a stable Syndecan-1 knock down (KdS1, and second to further decidualize the cells with progesterone. As a replacement for the ethically inapplicable embryo all cells were treated with the embryonic factors and secretion products interleukin-1β, interferon-γ, tumor necrosis factor-α, transforming growth factor-β1 and anti-Fas antibody to mimic the embryo contact. Detection of apoptosis was verified via Caspase ELISAs, PARP cleavage and Annexin V staining. Apoptosis-related proteins were investigated via antibody arrays and underlying signaling pathways were analyzed by Western blot. Non-decidualized endometrial stromal cells showed a resistance towards apoptosis which was rescinded by decidualization and Syndecan-1 knock down independent of decidualization. This was correlated with an altered expression of several pro- and anti-apoptotic proteins and connected to a higher activation of pro-survival Akt in non-differentiated St-T1 as an upstream mediator of apoptotis-related proteins. This study provides insight into the largely elusive process of implantation, proposing an important role for stromal cell apoptosis to successfully establish a pregnancy. The impact of Syndecan-1 in attenuating the apoptotic signal is particularly interesting in the

  7. ROS are critical for endometrial breakdown via NF-κB-COX-2 signaling in a female mouse menstrual-like model.

    Science.gov (United States)

    Wu, Bin; Chen, Xihua; He, Bin; Liu, Shuyan; Li, Yunfeng; Wang, Qianxing; Gao, Haijun; Wang, Shufang; Liu, Jianbing; Zhang, Shucheng; Xu, Xiangbo; Wang, Jiedong

    2014-09-01

    Progesterone withdrawal triggers endometrial breakdown and shedding during menstruation. Menstruation results from inflammatory responses; however, the role of reactive oxygen species (ROS) in menstruation remains unclear. In this study, we explored the role of ROS in endometrial breakdown and shedding. We found that ROS levels were significantly increased before endometrial breakdown in a mouse menstrual-like model. Vaginal smear inspection, morphology of uterine horns, and endometrial histology examination showed that a broad range of ROS scavengers significantly inhibited endometrial breakdown in this model. Furthermore, Western blot and immunohistochemical analysis showed that the intracellular translocation of p50 and p65 from the cytoplasm into the nucleus was blocked by ROS scavengers and real-time PCR showed that cyclooxygenase-2 (COX-2) mRNA expression was decreased by ROS scavengers. Similar changes also occurred in human stromal cells in vitro. Furthermore, Western blotting and real-time PCR showed that one ROS, hydrogen peroxide (H2O2), promoted translocation of p50 and p65 from the cytoplasm to the nucleus and increased COX-2 mRNA expression along with progesterone maintenance. The nuclear factor κB inhibitor MG132 reduced the occurrence of these changes in human stromal cells in vitro. Viewed as a whole, our results provide evidence that certain ROS are important for endometrial breakdown and shedding in a mouse menstrual-like model and function at least partially via nuclear factor-κB/COX-2 signaling. Similar changes observed in human stromal cells could also implicate ROS as important mediators of human menstruation.

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

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    Joshi, Ayesha; Ellenson, Lora Hedrick, E-mail: lora.ellenson@med.cornell.edu

    2011-07-01

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

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

    International Nuclear Information System (INIS)

    Joshi, Ayesha; Ellenson, Lora Hedrick

    2011-01-01

    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 +/- 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 +/- 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 ERα 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.

  10. Factors influencing endometrial thickness in postmenopausal women.

    Science.gov (United States)

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

    2014-07-01

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

  11. Endometrial and acute myeloid leukemia cancer genomes characterized

    Science.gov (United States)

    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.

  12. Endometrial cancer, types, prognosis, female hormones and antihormones

    DEFF Research Database (Denmark)

    Ulrich, L S G

    2011-01-01

    . Prognosis is also dependent on tumor differentiation and stage, and treatment should be adjusted accordingly. In this paper, the different types of endometrial cancer, staging, prognosis, diagnosis, prevention, treatment and their relationship to estrogen and other female hormones are reviewed....

  13. Molecular alterations in endometrial cancer : implications for clinical management

    NARCIS (Netherlands)

    Stelloo, E.

    2017-01-01

    Over the last decades, advances have been made in the treatment of endometrial cancer. The clinicopathological risk stratification for postoperative therapy has considerably reduced overtreatment by refining indications and introducing treatment with fewer side effects. Despite refinement in the use

  14. Epidemiology of Endometrial Cancer Consortium (E2C2)

    Science.gov (United States)

    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.

  15. Endometrial Adenocarcinoma and Mucocele of the Appendix: An Unusual Coexistence

    Directory of Open Access Journals (Sweden)

    Ioannis Kalogiannidis

    2013-01-01

    Full Text Available Appendiceal mucocele is a rare clinical entity, which is however quite often associated with mucinous ovarian tumor. The coexistence of mucinous cystadenoma of the appendix and endometrial adenocarcinoma has not been reported before. A 49-year-old woman presented to our clinic with postmenopausal bleeding and no other symptom. Endometrial biopsy revealed endometrial adenocarcinoma of endometrioid type (grade I. Preoperative CT scanning revealed an appendiceal mucocele, and a colonoscopy confirmed the diagnosis. The patient underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy and appendectomy. The final histopathological examination showed a mucinous cystadenoma of the appendix and confirmed the diagnosis of endometrioid endometrial adenocarcinoma. The coexistence of appendiceal mucocele and female genital tract pathology is rare. However, gynecologists should keep a high level of suspicion for such possible coexistence. Both the diagnostic approach and the therapeutic management should be multidisciplinary, most importantly with the involvement of general surgeons.

  16. Gene expression profiling reveals novel regulation by bisphenol-A in estrogen receptor-α-positive human cells

    International Nuclear Information System (INIS)

    Singleton, David W.; Feng, Yuxin; Yang, Jun; Puga, Alvaro; Lee, Adrian V.; Khan, Sohaib A.

    2006-01-01

    Bisphenol-A (BPA) shows proliferative actions in uterus and mammary glands and may influence the development of male and female reproductive tracts in utero or during early postnatal life. Because of its ability to function as an estrogen receptor (ER) agonist, BPA has the potential to disrupt normal endocrine signaling through regulation of ER target genes. Some genes are regulated by both estradiol (E2) and BPA, but those exclusive to either agent have not been described. Using a yeast strain incorporating a vitellogenin A2 ERE-LacZ reporter gene into the genome, we found that BPA induced expression of the reporter in colonies transformed with the ERα expression plasmid, illustrating BPA-mediated regulation within a chromatin context. Additionally, a reporter gene transiently transfected into the endometrial cancer (Ishikawa) cell line also showed BPA activity, although at 100-fold less potency than E2. To compare global gene expression in response to BPA and E2, we used a variant of the MCF-7 breast cancer cell line stably expressing HA-tagged ERα. Cultures were treated for 3 h with an ethanol vehicle, E2 (10 -8 M), or BPA (10 -6 M), followed by isolation of RNA and microarray analysis with the human U95A probe array (Affymetrix, Santa Clara, CA, USA). More than 300 genes were changed 2-fold or more by either or both agents, with roughly half being up-regulated and half down-regulated. A number of growth- and development-related genes, such as HOXC1 and C6, Wnt5A, Frizzled, TGFβ-2, and STAT inhibitor 2, were found to be affected exclusively by BPA. We used quantitative real-time PCR to verify regulation of the HOXC6 gene, which showed decreased expression of approximately 2.5-fold by BPA. These results reveal novel effects by BPA and E2, raising interesting possibilities regarding the role of endocrine disruptors in sexual development

  17. The role of miRNAs in endometrial cancer.

    Science.gov (United States)

    Vasilatou, Diamantina; Sioulas, Vasileios D; Pappa, Vasiliki; Papageorgiou, Sotirios G; Vlahos, Nikolaos F

    2015-01-01

    miRNAs are small noncoding RNAs that regulate gene expression at the post-transcriptional level. Since their discovery, miRNAs have been associated with every cell function including malignant transformation and metastasis. Endometrial cancer is the most common gynecologic malignancy. However, improvement should be made in interobserver agreement on histological typing and individualized therapeutic approaches. This article summarizes the role of miRNAs in endometrial cancer pathogenesis and treatment.

  18. Subcutaneous metastasis from endometrial cancer; case report and literature review

    OpenAIRE

    Nicolae Bacalbasa; Irina Balescu; Alexandru Filipescu

    2018-01-01

    Subcutaneous metastases from endometrial cancer are rare situations, only few cases being described so far. The main incriminated mechanisms leading to the apparition of such lesions include hematogenous and lymphatic spread. We present the case of a 66-year-old patient known with previous history of stage IIIA endometroid endometrial carcinoma initially treated by surgery and adjuvant chemotherapy who developed at 18 months follow-up a distant subcutaneous oligometastasis. At this time the p...

  19. Management of endometrial cancer: issues and controversies.

    Science.gov (United States)

    Bogani, G; Dowdy, S C; Cliby, W A; Ghezzi, F; Rossetti, D; Frigerio, L; Mariani, A

    2016-01-01

    Although endometrial cancer (EC) is the most common gynecologic cancer in developed countries, several aspects of its management are still controversial. In particular, the need to perform lymphadenectomy represents an important matter of discussion. Because of the discordant results in the literature, it is still not possible to draft any definitive conclusions regarding the therapeutic value of lymph node dissection. The present review discusses the role of lymphadenectomy in the setting of EC, risk factors for lymphatic spread, identification of patients at risk for lymph node dissemination, and the current evidence for adjuvant therapies in patients with positive nodes. Reasons for the difficulty in demonstrating any therapeutic value of pelvic and para-aortic lymphadenectomy are also discussed.

  20. Adjuvant chemotherapy for endometrial cancer after hysterectomy

    Science.gov (United States)

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

    2014-01-01

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

  1. IL-4-secreting eosinophils promote endometrial stromal cell proliferation and prevent Chlamydia-induced upper genital tract damage.

    Science.gov (United States)

    Vicetti Miguel, Rodolfo D; Quispe Calla, Nirk E; Dixon, Darlene; Foster, Robert A; Gambotto, Andrea; Pavelko, Stephen D; Hall-Stoodley, Luanne; Cherpes, Thomas L

    2017-08-15

    Genital Chlamydia trachomatis infections in women typically are asymptomatic and do not cause permanent upper genital tract (UGT) damage. Consistent with this presentation, type 2 innate and T H 2 adaptive immune responses associated with dampened inflammation and tissue repair are elicited in the UGT of Chlamydia -infected women. Primary C. trachomatis infection of mice also causes no genital pathology, but unlike women, does not generate Chlamydia -specific T H 2 immunity. Herein, we explored the significance of type 2 innate immunity for restricting UGT tissue damage in Chlamydia -infected mice, and in initial studies intravaginally infected wild-type, IL-10 -/- , IL-4 -/- , and IL-4Rα -/- mice with low-dose C. trachomatis inoculums. Whereas Chlamydia was comparably cleared in all groups, IL-4 -/- and IL-4Rα -/- mice displayed endometrial damage not seen in wild-type or IL-10 -/- mice. Congruent with the aberrant tissue repair in mice with deficient IL-4 signaling, we found that IL-4Rα and STAT6 signaling mediated IL-4-induced endometrial stromal cell (ESC) proliferation ex vivo, and that genital administration of an IL-4-expressing adenoviral vector greatly increased in vivo ESC proliferation. Studies with IL-4-IRES-eGFP (4get) reporter mice showed eosinophils were the main IL-4-producing endometrial leukocyte (constitutively and during Chlamydia infection), whereas studies with eosinophil-deficient mice identified this innate immune cell as essential for endometrial repair during Chlamydia infection. Together, our studies reveal IL-4-producing eosinophils stimulate ESC proliferation and prevent Chlamydia -induced endometrial damage. Based on these results, it seems possible that the robust type 2 immunity elicited by Chlamydia infection of human genital tissue may analogously promote repair processes that reduce phenotypic disease expression.

  2. Pelvic fractures following irradiation for endometrial carcinoma

    International Nuclear Information System (INIS)

    Konski, Andre; Sowers, Maryfran

    1996-01-01

    Purpose: To investigate the incidence and etiologic factors of pelvic fractures following radiation therapy for endometrial carcinoma. Methods and Materials: Tumor registry and radiation oncology records of patients treated for endometrial carcinoma at The Toledo Hospital between April 1989, and December 1992, were reviewed. Patients identified as having pelvic fractures without the presence of metastatic disease underwent total body mineral density measurement with dual x-ray densitometry. Results: Two of 75 patients (2.7%) were found to have pelvic fractures an average of 29 months from the completion of postoperative irradiation. One patient, who received preoperative irradiation, was also identified as having developed a fracture of the pelvis and was included in the analysis. All patients were treated prone with 10-15 MV photons in four fields daily. All three fracture patients received 45 Gy external beam radiation therapy. The two postoperative patients each received a single vaginal brachytherapy application delivering 20 Gy to 0.5 cm deep to the vaginal mucosa with a vaginal cylinder containing 30 mgRaeq 137 Cs. The preoperative patient received a single brachytherapy application with tandem and colpostats delivering 20 Gy to point A. Only one of the three fracture patients had the entire pubis included in the field of external beam treatment. One patient was taking nonsteroidal anti-inflammatory medication, one patient thyroid hormone replacement, and one patient was taking both types of medication. Conclusion: The etiology of pelvic fractures after irradiation is multifactorial. A complete medication history should be obtained, and care should be exercised in positioning the radiation fields to avoid inclusion of the entire pubis prior to the initiation of the radiation treatment

  3. Lipocalin 2 expression is associated with aggressive features of endometrial cancer

    International Nuclear Information System (INIS)

    Mannelqvist, Monica; Akslen, Lars A; Stefansson, Ingunn M; Wik, Elisabeth; Kusonmano, Kanthida; Raeder, Maria B; Øyan, Anne M; Kalland, Karl-Henning; Moses, Marsha A; Salvesen, Helga B

    2012-01-01

    Increased expression of lipocalin 2 (LCN2) has been observed in several cancers. The aim of the present study was to investigate LCN2 in endometrial cancer in relation to clinico-pathologic phenotype, angiogenesis, markers of epithelial-mesenchymal transition (EMT), and patient survival. Immunohistochemical staining was performed using a human LCN2 antibody on a population-based series of endometrial cancer patients collected in Hordaland County (Norway) during 1981-1990 (n = 256). Patients were followed from the time of primary surgery until death or last follow-up in 2007. The median follow-up time for survivors was 17 years. Gene expression data from a prospectively collected endometrial cancer series (n = 76) and a publicly available endometrial cancer series (n = 111) was used for gene correlation studies. Expression of LCN2 protein, found in 49% of the cases, was associated with non-endometrioid histologic type (p = 0.001), nuclear grade 3 (p = 0.001), >50% solid tumor growth (p = 0.001), ER and PR negativity (p = 0.028 and 0.006), and positive EZH2 expression (p < 0.001). LCN2 expression was significantly associated with expression of VEGF-A (p = 0.021), although not with other angiogenesis markers examined (vascular proliferation index, glomeruloid microvascular proliferation, VEGF-C, VEGF-D or bFGF2 expression). Further, LCN2 was not associated with several EMT-related markers (E-cadherin, N-cadherin, P-cadherin, β-catenin), nor with vascular invasion (tumor cells invading lymphatic or blood vessels). Notably, LCN2 was significantly associated with distant tumor recurrences, as well as with the S100A family of metastasis related genes. Patients with tumors showing no LCN2 expression had the best outcome with 81% 5-year survival, compared to 73% for intermediate and 38% for the small subgroup with strong LCN2 staining (p = 0.007). In multivariate analysis, LCN2 expression was an independent prognostic factor in addition to histologic grade and FIGO stage

  4. Pathologies of the uterine endometrial cavity: usual and unusual manifestations and pitfalls on magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Takeuchi, Mayumi; Matsuzaki, Kenji; Yoshida, Shusaku; Nishitani, Hiromu [University of Tokushima, Department of Radiology, Tokushima (Japan); Uehara, Hisanori [University of Tokushima, Department of Molecular and Environmental Pathology, Tokushima (Japan); Shimazu, Hideki [Oe Kyoudo Hospital, Department of Radiology (Japan)

    2005-11-01

    The endometrial cavity may demonstrate various imaging manifestations such as normal, reactive, inflammatory, and benign and malignant neoplasms. We evaluated usual and unusual magnetic resonance imaging (MRI) findings of the uterine endometrial cavity, and described the diagnostic clues to differential diagnoses. Surgically proven pathologies of the uterine endometrial cavity were evaluated retrospectively with pathologic correlation. The pathologies included benign endometrial neoplasms such as endometrial hyperplasia and polyp, malignant endometrial neoplasms such as endometrial carcinoma and carcinosarcoma, endometrial-myometrial neoplasm such as endometrial stromal sarcoma, pregnancy-related lesions in the endometrial cavity such as gestational trophoblastic diseases (hydatidiform mole, invasive mole and choriocarcinoma) and placental polyp, myometrial lesions simulating endometrial lesions such as submucosal leiomyoma and some adenomyosis, endometrial neoplasms simulating myometrial lesions such as adenomyomatous polyp and endometrial lesions arising in the hemicavity of a septate/bicornate uterus, and fluid collections in the uterine cavity (hydro/hemato/pyometra). It is important to recognize various imaging findings in these diseases, in order to make a correct preoperative diagnosis. (orig.)

  5. Comparative analysis between endometrial proteomes of pregnant and non-pregnant ewes during the peri-implantation period

    OpenAIRE

    Zhao, Haichao; Sui, Linlin; Miao, Kai; An, Lei; Wang, Dong; Hou, Zhuocheng; Wang, Rui; Guo, Min; Wang, Zhilong; Xu, Jiqiang; Wu, Zhonghong; Tian, Jianhui

    2015-01-01

    Background Early pregnancy failure has a profound impact on both human reproductive health and animal production. 2/3 pregnancy failures occur during the peri-implantation period; however, the underlying mechanism(s) remains unclear. Well-organized modification of the endometrium to a receptive state is critical to establish pregnancy. Aberrant endometrial modification during implantation is thought to be largely responsible for early pregnancy loss. Result In this study, using well-managed r...

  6. Long-term impact of preeclampsia on maternal endometrial cancer risk

    DEFF Research Database (Denmark)

    Hallum, Sara; Pinborg, Anja; Kamper-Jørgensen, Mads

    2016-01-01

    BACKGROUND: Endometrial cancer is mainly dependent on oestrogen exposure. Preeclampsia has shown to reduce oestrogen levels hence preeclampsia may affect later endometrial cancer risk. METHODS: We conducted a case-control study of 523 Danish women with endometrial cancer and 52 299controls during...... 1978-2010. The association between preeclampsia and later endometrial cancer was evaluated overall and according to preeclampsia onset and type of endometrial cancer in conditional logistic regression models. RESULTS: We observed no overall association between preeclampsia and endometrial cancer risk...... (OR=1.11 (95% CI 0.68-1.81)). This was true for all endometrial cancer subtypes. In an analysis of preeclampsia onset, however, we report a markedly increased risk of endometrial cancer following early-onset preeclampsia (OR=2.64 (95% CI 1.29-5.38)). CONCLUSIONS: Although we report no obvious...

  7. Reproducibility of current classifications of endometrial endometrioid glandular proliferations : further evidence supporting a simplified classification

    NARCIS (Netherlands)

    Ordi, Jaume; Bergeron, Christine; Hardisson, David; McCluggage, W. Glenn; Hollema, Harry; Felix, Ana; Soslow, Robert A.; Oliva, Esther; Tavassoli, Fattaneh A.; Alvarado-Cabrero, Isabel; Wells, Michael; Nogales, Francisco F.

    AimsTo compare the reproducibility of the current (2003) World Health Organization (WHO), endometrial intraepithelial neoplasia (EIN) and European Working Group (EWG) classifications of endometrial endometrioid proliferations. Methods and resultsNine expert gynaecological pathologists from Europe

  8. Prognostic significance of miR-205 in endometrial cancer.

    Directory of Open Access Journals (Sweden)

    Mihriban Karaayvaz

    Full Text Available microRNAs have emerged as key regulators of gene expression, and their altered expression has been associated with tumorigenesis and tumor progression. Thus, microRNAs have potential as both cancer biomarkers and/or potential novel therapeutic targets. Although accumulating evidence suggests the role of aberrant microRNA expression in endometrial carcinogenesis, there are still limited data available about the prognostic significance of microRNAs in endometrial cancer. The goal of this study is to investigate the prognostic value of selected key microRNAs in endometrial cancer by the analysis of archival formalin-fixed paraffin-embedded tissues.Total RNAs were extracted from 48 paired normal and endometrial tumor specimens using Trizol based approach. The expression of miR-26a, let-7g, miR-21, miR-181b, miR-200c, miR-192, miR-215, miR-200c, and miR-205 were quantified by real time qRT-PCR expression analysis. Targets of the differentially expressed miRNAs were quantified using immunohistochemistry. Statistical analysis was performed by GraphPad Prism 5.0.The expression levels of miR-200c (P<0.0001 and miR-205 (P<0.0001 were significantly increased in endometrial tumors compared to normal tissues. Kaplan-Meier survival analysis revealed that high levels of miR-205 expression were associated with poor patient overall survival (hazard ratio, 0.377; Logrank test, P = 0.028. Furthermore, decreased expression of a miR-205 target PTEN was detected in endometrial cancer tissues compared to normal tissues.miR-205 holds a unique potential as a prognostic biomarker in endometrial cancer.

  9. Differentiation of the endometrial macrophage during pregnancy in the cow.

    Directory of Open Access Journals (Sweden)

    Lilian J Oliveira

    Full Text Available BACKGROUND: The presence of conceptus alloantigens necessitates changes in maternal immune function. One player in this process may be the macrophage. In the cow, there is large-scale recruitment of macrophages expressing CD68 and CD14 to the uterine endometrium during pregnancy. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, the function of endometrial macrophages during pregnancy was inferred by comparison of the transcriptome of endometrial CD14(+ cells isolated from pregnant cows as compared to that of blood CD14(+ cells. The pattern of gene expression was largely similar for CD14(+ cells from both sources, suggesting that cells from both tissues are from the monocyte/macrophage lineage. A total of 1,364 unique genes were differentially expressed, with 680 genes upregulated in endometrial CD14(+ cells as compared to blood CD14(+ cells and with 674 genes downregulated in endometrial CD14(+ cells as compared to blood CD14(+ cells. Twelve genes characteristic of M2 activated macrophages (SLCO2B1, GATM, MRC1, ALDH1A1, PTGS1, RNASE6, CLEC7A, DPEP2, CD163, CCL22, CCL24, and CDH1 were upregulated in endometrial CD14(+ cells. M2 macrophages play roles in immune regulation, tissue remodeling, angiogenesis and apoptosis. Consistent with a role in tissue remodeling, there was over-representation of differentially expressed genes in endometrium for three ontologies related to proteolysis. A role in apoptosis is suggested by the observation that the most overrepresented gene in endometrial CD14(+ cells was GZMA. CONCLUSIONS: Results indicate that at least a subpopulation of endometrial macrophages cells differentiates along an M2 activation pathway during pregnancy and that the cells are likely to play roles in immune regulation, tissue remodeling, angiogenesis, and apoptosis.

  10. Endometrial stromal tumors with sex cord-like elements: a case report

    African Journals Online (AJOL)

    Endometrial stromal nodules are rare. They represent less than a quarter of endometrial stromal tumors. Clement and Scully described as variants of endometrial stromal nodules two types of tumor ressembling ovarian sex cord tumors. Type I is tumor that resembles focally an ovarian sex cord tumor which can be ...

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  15. PIpelle Prospective ENDOmetrial carcinoma (PIPENDO) study, pre-operative recognition of high risk endometrial carcinoma: a multicentre prospective cohort study

    International Nuclear Information System (INIS)

    Visser, Nicole C. M.; Bulten, Johan; Wurff, Anneke A. M. van der; Boss, Erik A.; Bronkhorst, Carolien M.; Feijen, Harrie W. H.; Haartsen, Joke E.; Herk, Hilde A. D. M. van; Kievit, Ineke M. de; Klinkhamer, Paul J. J. M.; Pijlman, Brenda M.; Snijders, Marc P. M. L.; Vandenput, Ingrid; Vos, M. Caroline; Wit, Peter E. J. de; Poll-Franse, Lonneke V. van de; Massuger, Leon F.A.G.; Pijnenborg, Johanna M. A.

    2015-01-01

    Endometrial carcinoma is the most common gynaecologic malignancy in industrialised countries and the incidence is still rising. Primary treatment is based on preoperative risk classification and consists in most cases of hysterectomy with bilateral salpingo-oophorectomy. In patients with serous and clear cell histology a complete surgical staging is mandatory. However, in routine clinical practice final histology regularly does not correspond with the preoperative histological diagnosis. This results in both over and under treatment. The aim of this multicentre, prospective cohort study is to select a panel of prognostic biomarkers to improve preoperative diagnosis of endometrial carcinoma in order to identify those patients that need extended surgery and/or additional treatment. Additionally, we will determine whether incorporation of cervical cytology and comorbidity could improve this preoperative risk classification. All patients treated for endometrial carcinoma in the participating hospitals from September 2011 till December 2013 are included. Patient characteristics, as well as comorbidity are registered. Patients without preoperative histology, history of hysterectomy and/or endometrial carcinoma or no surgical treatment including hysterectomy are excluded. The preoperative histology and final pathology will be reviewed and compared by expert pathologists. Additional immunohistochemical analysis of IMP3, p53, ER, PR, MLH1, PTEN, beta-catenin, p16, Ki-67, stathmin, ARID1A and L1CAM will be performed. Preoperative histology will be compared with the final pathology results. Follow-up will be at least 24 months to determine risk factors for recurrence and outcome. This study is designed to improve surgical treatment of endometrial carcinoma patients. A total of 432 endometrial carcinoma patients were enrolled between 2011 and 2013. Follow-up will be completed in 2015. Preoperative histology will be evaluated systematically and background endometrium will be

  16. Analysis of abnormally thickened endometrial patterns on transvaginal sonography

    International Nuclear Information System (INIS)

    Lee, Myung Sook; Cho, Hyeun Cha

    1999-01-01

    To determine whether the transvaginal sonographic appearance of the thickened endometrium can help to predict the underlying endometrial pathologic process. The sonogram reports of fall 41 pre- and 21 postmenopausal women who underwent transvaginal sonogram were retrospectively analyzed. The women undergoing estrogen replacement therapy, tamoxifen therapy or having abnormal cervical cytology were excluded from this study. The analysis of sonographic and histologic results was performed in all patients. Three distinct sonographic patterns were encountered. Type I consisted of heterogeneous endometrial thickening with internal hypoechoic areas (normal [n=4], polyp [n=1] and cancer [n=4] in premenopausal women and cancer [n=4] in postmenopausal women). Type II consisted of echogenic endometrial thickening with or without tiny cysts (normal[n=5], and hyperplasia [n=7] in premenopausal women and normal [n=4], polyp [n=2], and hyperplasia [n=1] in postmenopausal women). Type III consisted of localized well defined endoluminal lesion (normal [n=1], polyp [n=14], hyperplasia [n=1], cancer [n=1], and submucosal mass [n=3] in premenopausal women and normal [n=4], polyp [n=2],submucosal mass [n=3], and hematoma [n=1] in postmenopausal women). The measurement of the endometrial thickness combined with analysis of sonographic echo patterns may be helpful in prediction and differentiation of endometrial disease in pre- and postmenopausal women. Also it can contribute to avoiding unnecessary D and C.

  17. Histopathological pattern of abnormal uterine bleeding in endometrial biopsies.

    Science.gov (United States)

    Vaidya, S; Lakhey, M; Vaidya, S; Sharma, P K; Hirachand, S; Lama, S; KC, S

    2013-03-01

    Abnormal uterine bleeding is a common presenting complaint in gyanecology out patient department. Histopathological evaluation of the endometrial samples plays a significant role in the diagnosis of abnormal uterine bleeding. This study was carried out to determine the histopathological pattern of the endometrium in women of various age groups presenting with abnormal uterine bleeding. Endometrial biopsies and curettings of patients presenting with abnormal uterine bleeding was retrospectively studied. A total of 403 endometrial biopsies and curettings were analyzed. The age of the patients ranged from 18 to 70 years. Normal cyclical endometrium was seen in 165 (40.94%) cases, followed by 54 (13.40%) cases of disordered proliferative endometrium and 44 (10.92%) cases of hyperplasia. Malignancy was seen in 10 (2.48%) cases. Hyperplasia and malignancy were more common in the perimenopausal and postmenopausal age groups. Histopathological examination of endometrial biopsies and curettings in patients presenting with abnormal uterine bleeding showed a wide spectrum of changes ranging from normal endometrium to malignancy. Endometrial evaluation is specially recommended in women of perimenopausal and postmenopausal age groups presenting with AUB, to rule out a possibility of any preneoplastic condition or malignancy.

  18. Non-Coding RNAs and Endometrial Cancer

    Directory of Open Access Journals (Sweden)

    Cristina Vallone

    2018-03-01

    Full Text Available Non-coding RNAs (ncRNAs are involved in the regulation of cell metabolism and neoplastic transformation. Recent studies have tried to clarify the significance of these information carriers in the genesis and progression of various cancers and their use as biomarkers for the disease; possible targets for the inhibition of growth and invasion by the neoplastic cells have been suggested. The significance of ncRNAs in lung cancer, bladder cancer, kidney cancer, and melanoma has been amply investigated with important results. Recently, the role of long non-coding RNAs (lncRNAs has also been included in cancer studies. Studies on the relation between endometrial cancer (EC and ncRNAs, such as small ncRNAs or micro RNAs (miRNAs, transfer RNAs (tRNAs, ribosomal RNAs (rRNAs, antisense RNAs (asRNAs, small nuclear RNAs (snRNAs, Piwi-interacting RNAs (piRNAs, small nucleolar RNAs (snoRNAs, competing endogenous RNAs (ceRNAs, lncRNAs, and long intergenic ncRNAs (lincRNAs have been published. The recent literature produced in the last three years was extracted from PubMed by two independent readers, which was then selected for the possible relation between ncRNAs, oncogenesis in general, and EC in particular.

  19. Incisional Recurrences After Endometrial Cancer Surgery.

    Science.gov (United States)

    Bogani, Giorgio; Dowdy, Sean C; Cliby, William A; Gostout, Bobbie S; Kumar, Sanjeev; Ghezzi, Fabio; Multinu, Francesco; Mariani, Andrea

    2015-11-01

    The aim of the present study was to estimate the incisional recurrence (IR) rate after endometrial cancer (EC) staging surgery and analyze characteristics of affected patients. We retrospectively searched for patients with EC at 2 institutions and analyzed the occurrence of IR after open, laparoscopic, or robotic surgery. Additionally, a review of the literature was performed. Out of 2,636 patients with EC, 1,732 (65.7%), 461 (17.5%), and 443 (16.8%) had open, laparoscopic, and robotic surgery, respectively. Only 3 patients (0.11%) had IR, all after open surgery. Additionally, 38 cases of IR were identified from the literature. Patients with non-isolated IR had worse overall survival than patients with isolated IR (p=0.04). Among this latter group, combined treatments may be associated with improved survival outcome. IR after EC surgery is rare and may occur after minimally-invasive or open operations. Combination of local and systemic treatments may provide favorable outcomes for patients with isolated IR. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

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

    NARCIS (Netherlands)

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

    2016-01-01

    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

  1. E-cadherin and CD10 expression in atypical hyperplastic and malignant endometrial lesions

    International Nuclear Information System (INIS)

    Ahmed, A.R.H.; Muhammad, E.M.S.

    2014-01-01

    Background: Loss of E-cadherin is a critical step for development and progression of malignant tumors. CD10; a marker of non-neoplastic and neoplastic endometrial stroma, is associated with aggressiveness of many epithelial malignancies. Aims: To evaluate expression and correlation of E-cadherin and CD10 in endometrial lesions and their possible role in differentiating atypical endometrial hyperplasia from endometrial carcinoma. The association of E-cadherin and CD10 expression with clinico-pathological parameters of endometrial carcinoma was also investigated. Materials and methods: Fifty four cases including 28 endometrial carcinomas; 19 endometrial hyperplasia and 7 cases of normal endometrial changes were enrolled for this study. The expression of E-cadherin and CD10 was evaluated by immunohistochemistry using the streptavidin–biotin technique. Results: There was a strong association between malignant change of endometrial glands and membrano- cytoplasmic localization of E-cadherin (p< 0.001). Expression of E-cadherin but not CD10 was significantly higher in endometrial carcinomas compared to atypical endometrial hyperplasia (p < 0.01). Expression of E-cadherin was not associated with CD10 expression in different endometrial lesions. High grade tumors expressed low levels of both E-cadherin (p<0.01) and CD10 (p < 0.05) and serous endometrial carcinoma had low E-cadherin and CD10 expression compared to endometrioid carcinoma (p< 0.01 and <0.05, respectively). Expression of both molecules showed no association with depth of tumor invasion or FIGO stage. Tumors with lower E-cadherin or CD10 expression had higher rates of vascular tumor emboli (p< 0.01 and <0.07, respectively). Conclusions: Although expression of E-cadherin and CD10 in endometrial lesions was not correlated, reduced expression of both molecules could be critical for progression of endometrial carcinoma.

  2. Endometrial ablation in the management of abnormal uterine bleeding.

    Science.gov (United States)

    Laberge, Philippe; Leyland, Nicholas; Murji, Ally; Fortin, Claude; Martyn, Paul; Vilos, George; Leyland, Nicholas; Wolfman, Wendy; Allaire, Catherine; Awadalla, Alaa; Dunn, Sheila; Heywood, Mark; Lemyre, Madeleine; Marcoux, Violaine; Potestio, Frank; Rittenberg, David; Singh, Sukhbir; Yeung, Grace

    2015-04-01

    Abnormal uterine bleeding (AUB) is the direct cause of a significant health care burden for women, their families, and society as a whole. Up to 30% of women will seek medical assistance for the problem during their reproductive years. To provide current evidence-based guidelines on the techniques and technologies used in endometrial ablation (EA), a minimally invasive technique for the management of AUB of benign origin. Members of the guideline committee were selected on the basis of individual expertise to represent a range of practical and academic experience in terms of both location in Canada and type of practice, as well as subspecialty expertise and general background in gynaecology. The committee reviewed all available evidence in the English medical literature, including published guidelines, and evaluated surgical and patient outcomes for the various EA techniques. Recommendations were established by consensus. Published literature was retrieved through searches of MEDLINE and The Cochrane Library in 2013 and 2014 using appropriate controlled vocabulary and key words (endometrial ablation, hysteroscopy, menorrhagia, heavy menstrual bleeding, AUB, hysterectomy). RESULTS were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies written in English from January 2000 to November 2014. Searches were updated on a regular basis and incorporated in the guideline to December 2014. Grey (unpublished) literature was identifies through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table 1). This document reviews the evidence regarding the available techniques and technologies for EA

  3. Infertility and incident endometrial cancer risk: a pooled analysis from the epidemiology of endometrial cancer consortium (E2C2)

    Science.gov (United States)

    Yang, H P; Cook, L S; Weiderpass, E; Adami, H-O; Anderson, K E; Cai, H; Cerhan, J R; Clendenen, T V; Felix, A S; Friedenreich, C M; Garcia-Closas, M; Goodman, M T; Liang, X; Lissowska, J; Lu, L; Magliocco, A M; McCann, S E; Moysich, K B; Olson, S H; Petruzella, S; Pike, M C; Polidoro, S; Ricceri, F; Risch, H A; Sacerdote, C; Setiawan, V W; Shu, X O; Spurdle, A B; Trabert, B; Webb, P M; Wentzensen, N; Xiang, Y-B; Xu, Y; Yu, H; Zeleniuch-Jacquotte, A; Brinton, L A

    2015-01-01

    Background: Nulliparity is an endometrial cancer risk factor, but whether or not this association is due to infertility is unclear. Although there are many underlying infertility causes, few studies have assessed risk relations by specific causes. Methods: We conducted a pooled analysis of 8153 cases and 11 713 controls from 2 cohort and 12 case-control studies. All studies provided self-reported infertility and its causes, except for one study that relied on data from national registries. Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). Results: Nulliparous women had an elevated endometrial cancer risk compared with parous women, even after adjusting for infertility (OR=1.76; 95% CI: 1.59–1.94). Women who reported infertility had an increased risk compared with those without infertility concerns, even after adjusting for nulliparity (OR=1.22; 95% CI: 1.13–1.33). Among women who reported infertility, none of the individual infertility causes were substantially related to endometrial cancer. Conclusions: Based on mainly self-reported infertility data that used study-specific definitions of infertility, nulliparity and infertility appeared to independently contribute to endometrial cancer risk. Understanding residual endometrial cancer risk related to infertility, its causes and its treatments may benefit from large studies involving detailed data on various infertility parameters. PMID:25688738

  4. Childhood BMI growth trajectories and endometrial cancer risk

    DEFF Research Database (Denmark)

    Aarestrup, Julie; Gamborg, Michael; Tilling, Kate

    2017-01-01

    Previously, we found that excess weight already in childhood has positive associations with endometrial cancer, however, associations with changes in body mass index (BMI) during childhood are not well understood. Therefore, we examined whether growth in childhood BMI is associated with endometrial...... cancer and its sub-types. A cohort of 155,505 girls from the Copenhagen School Health Records Register with measured weights and heights at the ages of 6 to 14 years and born 1930-89 formed the analytical population. BMI was transformed to age-specific z-scores. Using linear spline multilevel models......, each girl's BMI growth trajectory was estimated as the deviance from the average trajectory for three different growth periods (6.25-7.99, 8.0-10.99, 11.0-14.0 years). Via a link to health registers, 1020 endometrial cancer cases were identified, and Cox regressions were performed. A greater gain...

  5. Diagnosis of endometrial tuberculosis: culture versus histopathological examination

    International Nuclear Information System (INIS)

    Zaman, G.; Karamat, K.A.; Hafeez-ud-Din; Yousaf, A.; Abbasi, S.A.; Rafi, S.

    2002-01-01

    Objective: To compare the relative efficacy of histopathological examination and culture method in the diagnosis of endometrial tuberculosis. Design: It was a prospective, comparative in-vitro study. Place and Duration of Study: The study was conducted at the Armed Forces Institute of Pathology, Rawalpindi and Department of Obstetrics and Gynecology, Military Hospital, Rawalpindi from August 1998 to April 1999. Materiel and Methods: A total number of 50 cases of primary and secondary infertility were selected. Endometrial biopsies of all patients were subjected to histopathological as well as culture examination on BACTEC. Results: Culture method yielded 10% (n=5) positive results compared with 6% (n=3) positive results obtained by histopathological examination. P value was 0.096 by chi-square test. Conclusion: Culture is a more effective method compared with histopathological examination in the diagnosis of endometrial tuberculosis. (author)

  6. 18F-FDG-PET/CT in Endometrial Carcinoma

    International Nuclear Information System (INIS)

    Jeon, Tae Joo

    2008-01-01

    Endometrial carcinoma is one of the most common gynecologic malignancies and which is predominant in postmenopausal women. Clinically many patients are hospitalized in early stage due to clinical sign and symptom such as vaginal bleeding and in this case, patient's prognosis is known to be good. However, considerable number of patients with advanced and relapsed disease reveal poor prognosis. Therefore, exact staging work up is essential for proper treatment as is primary lesion detection. 18 F-FDG-PET has been widely used for the evaluation of gynecologic malignancies such as cervical carcinoma and ovarian cancer. In contrast, FDG PET application to endometrial carcinoma is limited until now and there is no sufficient data to validate the usefulness of FDG PET for this disease yet. However, several studies showed promising results that FDG PET is sensitive and specific in detection of recurrent or metastatic lesions. Therefore further active investigation in this field can facilitate the use of FDG PET for endometrial carcinoma

  7. Hormone replacement therapy and the risk of endometrial cancer

    DEFF Research Database (Denmark)

    Sjögren, Lea L; Mørch, Lina Steinrud; Løkkegaard, Ellen

    2016-01-01

    BACKGROUND: In 1975, estrogen only was found to be associated with an increased risk of endometrial cancer. In November 2015, NICE guidelines on hormone therapy were published that did not take this risk into account. AIM: This systematic literature review assesses the safety of estrogen plus...... progestin therapy according to the risk of endometrial cancer, while considering both regimen and type of progestin. METHODS: PubMed, EMBASE and the Cochrane Library were searched, resulting in the identification of 527 published articles on menopausal women with intact uteri treated with estrogen only......, estrogen plus progestin or tibolone for a minimum of one year. Risk of endometrial cancer was compared to placebo or never users and measured as relative risk, hazard or odds ratio. RESULTS: 28 studies were included. The observational literature found an increased risk among users of estrogen alone...

  8. Mutations of the KRAS oncogene in endometrial hyperplasia and carcinoma.

    Directory of Open Access Journals (Sweden)

    Wiesława Niklińska

    2009-05-01

    Full Text Available The aim of this study was to examine the prevalence and clinicopathological significance of KRAS point mutation in endometrial hyperplasia and carcinoma. We analysed KRAS in 11 cases of complex atypical hyperplasia and in 49 endometrial carcinomas using polymerase chain reaction associated with restriction fragment length polymorphism (PCR-RFPL. Point mutations at codon 12 of KRAS oncogene were identified in 7 of 49 (14,3% tumor specimens and in 2 of 11 (18,2% hyperplasias. No correlation was found between KRAS gene mutation and age at onset, histology, grade of differentiation and clinical stage. We conclude that KRAS mutation is a relatively common event in endometrial carcinogenesis, but with no prognostic value.

  9. A Gata2-Dependent Transcription Network Regulates Uterine Progesterone Responsiveness and Endometrial Function

    Directory of Open Access Journals (Sweden)

    Cory A. Rubel

    2016-10-01

    Full Text Available Altered progesterone responsiveness leads to female infertility and cancer, but underlying mechanisms remain unclear. Mice with uterine-specific ablation of GATA binding protein 2 (Gata2 are infertile, showing failures in embryo implantation, endometrial decidualization, and uninhibited estrogen signaling. Gata2 deficiency results in reduced progesterone receptor (PGR expression and attenuated progesterone signaling, as evidenced by genome-wide expression profiling and chromatin immunoprecipitation. GATA2 not only occupies at and promotes expression of the Pgr gene but also regulates downstream progesterone responsive genes in conjunction with the PGR. Additionally, Gata2 knockout uteri exhibit abnormal luminal epithelia with ectopic TRP63 expressing squamous cells and a cancer-related molecular profile in a progesterone-independent manner. Lastly, we found a conserved GATA2-PGR regulatory network in both human and mice based on gene signature and path analyses using gene expression profiles of human endometrial tissues. In conclusion, uterine Gata2 regulates a key regulatory network of gene expression for progesterone signaling at the early pregnancy stage.

  10. Identification of endometrial cancer methylation features using combined methylation analysis methods.

    Directory of Open Access Journals (Sweden)

    Michael P Trimarchi

    Full Text Available DNA methylation is a stable epigenetic mark that is frequently altered in tumors. DNA methylation features are attractive biomarkers for disease states given the stability of DNA methylation in living cells and in biologic specimens typically available for analysis. Widespread accumulation of methylation in regulatory elements in some cancers (specifically the CpG island methylator phenotype, CIMP can play an important role in tumorigenesis. High resolution assessment of CIMP for the entire genome, however, remains cost prohibitive and requires quantities of DNA not available for many tissue samples of interest. Genome-wide scans of methylation have been undertaken for large numbers of tumors, and higher resolution analyses for a limited number of cancer specimens. Methods for analyzing such large datasets and integrating findings from different studies continue to evolve. An approach for comparison of findings from a genome-wide assessment of the methylated component of tumor DNA and more widely applied methylation scans was developed.Methylomes for 76 primary endometrial cancer and 12 normal endometrial samples were generated using methylated fragment capture and second generation sequencing, MethylCap-seq. Publically available Infinium HumanMethylation 450 data from The Cancer Genome Atlas (TCGA were compared to MethylCap-seq data.Analysis of methylation in promoter CpG islands (CGIs identified a subset of tumors with a methylator phenotype. We used a two-stage approach to develop a 13-region methylation signature associated with a "hypermethylator state." High level methylation for the 13-region methylation signatures was associated with mismatch repair deficiency, high mutation rate, and low somatic copy number alteration in the TCGA test set. In addition, the signature devised showed good agreement with previously described methylation clusters devised by TCGA.We identified a methylation signature for a "hypermethylator phenotype" in

  11. Structural changes in endometrial basal glands during menstruation.

    Science.gov (United States)

    Garry, R; Hart, R; Karthigasu, K A; Burke, C

    2010-09-01

    To prospectively observe the changes occurring in endometrial glandular morphology during menstrual shedding and regeneration. Prospective observational study. The academic gynaecological endoscopy unit of a university teaching hospital. Population Thirteen patients investigated for a variety of benign, non-infective gynaecological disorders during the active bleeding phase of the menstrual cycle. The morphological appearances of concurrent histological and scanning electron microscopic images of endometrium taken at different stages of the active bleeding phase of menstruation were studied and correlated with the simultaneous immunohistochemical expression of the Ki-67 proliferation marker and the CD68 marker of macrophage activity. Change in morphology of endometrial glands at various stages of menstruation. Endometrial glands within the basalis show evidence of apoptosis and associated macrophage activity immediately before and during menstruation. There is subsequent destruction and removal of old secretory glandular epithelial elements, and rapid replacement with new narrow glands lined with small epithelial cells. There is no evidence of mitotic cell division or expression of Ki-67 in the glandular cells during this replacement process, but there is evidence of marked macrophage activity prior to glandular cell loss. Early endometrial epithelial repair after menstruation is not a consequence of mitotic cell division. It occurs without evidence of Ki-67 expression. There is structural evidence of programmed cell death and intense macrophage activity associated with glandular remodelling. Dead epithelial cells are shed from the glands and accumulate within the endometrial cavity to be replaced by new small epithelial cells that appear to arise by differentiation of the surrounding stromal cells. We propose that these stromal cells are endometrial progenitor/stem cells.

  12. Robotic surgery in supermorbidly obese patients with endometrial cancer.

    Science.gov (United States)

    Stephan, Jean-Marie; Goodheart, Michael J; McDonald, Megan; Hansen, Jean; Reyes, Henry D; Button, Anna; Bender, David

    2015-07-01

    Morbid obesity is a known risk factor for the development of endometrial cancer. Several studies have demonstrated the overall feasibility of robotic-assisted surgical staging for endometrial cancer as well as the benefits of robotics compared with laparotomy. However, there have been few reports that have evaluated robotic surgery for endometrial cancer in the supermorbidly obese population (body mass index [BMI], ≥50 kg/m(2)). We sought to evaluate safety, feasibility, and outcomes for supermorbidly obese patients who undergo robotic surgery for endometrial cancer, compared with patients with lower body mass indices. We performed a retrospective chart review of 168 patients with suspected early-stage endometrial adenocarcinoma who underwent robotic surgery for the management of their disease. Analysis of variance and univariate logistic regression were used to compare patient characteristics and surgical variables across all body weights. Cox proportional hazard regression was used to determine the impact of body weight on recurrence-free and overall survival. The mean BMI of our cohort was 40.9 kg/m(2). Median follow up was 31 months. Fifty-six patients, 30% of which had grade 2 or 3 tumors, were supermorbidly obese with a BMI of ≥50 kg/m(2) (mean, 56.3 kg/m(2)). A comparison between the supermorbidly obese and lower-weight patients demonstrated no differences in terms of length of hospital stay, blood loss, complication rates, numbers of pelvic and paraaortic lymph nodes retrieved, or recurrence and survival. There was a correlation between BMI and conversion to an open procedure, in which the odds of conversion increased with increasing BMI (P = .02). Offering robotic surgery to supermorbidly obese patients with endometrial cancer is a safe and feasible surgical management option. When compared with patients with a lower BMI, the supermorbidly obese patient had a similar outcome, length of hospital stay, blood loss, complications, and numbers of lymph

  13. Frequency of endometrial carcinoma in patients with postmenopausal bleeding

    International Nuclear Information System (INIS)

    Yousaf, S.; Shaheen, M.; Rana, T.

    2010-01-01

    Introduction: Postmenopausal bleeding (PMB) is defined as bleeding that occurs after 1 year of amenorrhea in a woman who is not receiving hormone replacement therapy (HRT). About 10% of women with postmenopausal bleeding have a primary or secondary malignancy. Common malignancies among them are endometrial cancer (80%), cervical cancer or an ovarian tumour. Endometrial cancer is the second most common cancer associated with hereditary non-polyposis colorectal cancer. Ninety percent of patients have benign causes. Objective: The objective of this study was to determine the frequency of endometrial carcinoma in patients with post-menopausal bleeding. Study Design: Descriptive case series study. Setting: Department of obstetrics and gynaecology, Lady Willingdon, Lahore. Duration of Study: This study was conducted over a period of six months from January, 1 2009 to June 30, 2009. Subjects and Methods: 50 cases with postmenopausal bleeding. Results: During the period of this study a total number of 50 consecutive patients who met inclusion criteria were enrolled in the study. Ages of the patients who presented with PMB ranged between 48 years and 80 years with a mean age of 59 years. Malignancy was found in 18 out of 50 cases (36%).Cases with endometrial CA were 14 out of 50 cases (28%) and CA cervix constituted 4 out of 50 cases (8%). Benign pathology was more frequent (64%). 13 of 50 cases (26%) had hyperplasia out of which 1 case (2%) was of atypical hyperplasia. Endometrial polyp was found in 4 of 50 cases (8%). 3 of 50 cases (6%) had chronic endometritis. 5 of 50 cases (10%) had chronic cervicitis. While 7 cases (14%) had postmenopausal bleeding due to decubitus ulcer of uterovaginal prolapse. Among malignancies (36%), endometrial cancer is the most frequent malignancy in women with postmenopausal bleeding with mean age of 65 years. Conclusion: In this study it was concluded that the majority of cases of PMB would be expected to be suffering from benign problems

  14. Premenopausal abnormal uterine bleeding and risk of endometrial cancer.

    Science.gov (United States)

    Pennant, M E; Mehta, R; Moody, P; Hackett, G; Prentice, A; Sharp, S J; Lakshman, R

    2017-02-01

    Endometrial biopsies are undertaken in premenopausal women with abnormal uterine bleeding but the risk of endometrial cancer or atypical hyperplasia is unclear. To conduct a systematic literature review to establish the risk of endometrial cancer and atypical hyperplasia in premenopausal women with abnormal uterine bleeding. Search of PubMed, Embase and the Cochrane Library from database inception to August 2015. Studies reporting rates of endometrial cancer and/or atypical hyperplasia in women with premenopausal abnormal uterine bleeding. Data were independently extracted by two reviewers and cross-checked. For each outcome, the risk and a 95% CI were estimated using logistic regression with robust standard errors to account for clustering by study. Sixty-five articles contributed to the analysis. Risk of endometrial cancer was 0.33% (95% CI 0.23-0.48%, n = 29 059; 97 cases) and risk of endometrial cancer or atypical hyperplasia was 1.31% (95% CI 0.96-1.80, n = 15 772; 207 cases). Risk of endometrial cancer was lower in women with heavy menstrual bleeding (HMB) (0.11%, 95% CI 0.04-0.32%, n = 8352; 9 cases) compared with inter-menstrual bleeding (IMB) (0.52%, 95% CI 0.23-1.16%, n = 3109; 14 cases). Of five studies reporting the rate of atypical hyperplasia in women with HMB, none identified any cases. The risk of endometrial cancer or atypical hyperplasia in premenopausal women with abnormal uterine bleeding is low. Premenopausal women with abnormal uterine bleeding should first undergo conventional medical management. Where this fails, the presence of IMB and older age may be indicators for further investigation. Further research into the risks associated with age and the cumulative risk of co-morbidities is needed. Contrary to practice, premenopausal women with heavy periods or inter-menstrual bleeding rarely require biopsy. © 2016 The Authors BJOG An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd on behalf of Royal

  15. Microarray profiling of progesterone-regulated endometrial genes during the rhesus monkey secretory phase

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    Okulicz William C

    2004-07-01

    Full Text Available Abstract Background In the endometrium the steroid hormone progesterone (P, acting through its nuclear receptors, regulates the expression of specific target genes and gene networks required for endometrial maturation. Proper endometrial maturation is considered a requirement for embryo implantation. Endometrial receptivity is a complex process that is spatially and temporally restricted and the identity of genes that regulate receptivity has been pursued by a number of investigators. Methods In this study we have used high density oligonucleotide microarrays to screen for changes in mRNA transcript levels between normal proliferative and adequate secretory phases in Rhesus monkey artificial menstrual cycles. Biotinylated cRNA was prepared from day 13 and days 21–23 of the reproductive cycle and transcript levels were compared by hybridization to Affymetrix HG-U95A arrays. Results Of ~12,000 genes profiled, we identified 108 genes that were significantly regulated during the shift from a proliferative to an adequate secretory endometrium. Of these genes, 39 were up-regulated at days 21–23 versus day 13, and 69 were down-regulated. Genes up-regulated in P-dominant tissue included: secretoglobin (uteroglobin, histone 2A, polo-like kinase (PLK, spermidine/spermine acetyltransferase 2 (SAT2, secretory leukocyte protease inhibitor (SLPI and metallothionein 1G (MT1G, all of which have been previously documented as elevated in the Rhesus monkey or human endometrium during the secretory phase. Genes down-regulated included: transforming growth factor beta-induced (TGFBI or BIGH3, matrix metalloproteinase 11 (stromelysin 3, proenkephalin (PENK, cysteine/glycine-rich protein 2 (CSRP2, collagen type VII alpha 1 (COL7A1, secreted frizzled-related protein 4 (SFRP4, progesterone receptor membrane component 1 (PGRMC1, chemokine (C-X-C ligand 12 (CXCL12 and biglycan (BGN. In addition, many novel/unknown genes were also identified. Validation of array data

  16. Does the endometrial gene expression of fertile women vary within and between cycles?

    Science.gov (United States)

    Evans, Gloria E; Phillipson, Gregory T M; Sykes, Peter H; McNoe, Les A; Print, Cristin G; Evans, John J

    2018-01-23

    Does gene expression of putative endometrial implantation markers vary in expression between menstrual cycles? In fertile women the expression of certain genes exhibits a pattern of stable regulation.which is not affected even when sampled twice in one cycle. Successful implantation occurs in a minority of IVF embryo transfers. In contrast to knowledge regarding the ovulatory process, there is a sparse understanding of endometrial genes critical to implantation. This lack of knowledge hinders progress in this field. Endometrial pipelle samples were collected based on blood endocrinological markers at 2 and 7 days post initial LH surge. Five samples were collected over four cycles where the interval between collections ranged from sequential months to three years. Six fertile women attending an IVF clinic for male factor infertility, had samples collected. Global gene expression profiles were obtained from laser-microdissected, endometrial glands and stroma. Nineteen potential proliferation, cytokine and adhesion markers based on previous validated reports were studied. There was a significant modification between LH+2 and LH+7 of expression for 23 genes-11 in 8 in glands and stroma, 4 in stroma only and 3 in glands only suggesting stable, controlled regulation. Nevertheless, genes exhibited individual characteristics, e.g MKI67 exhibited lower expression at LH+7 than LH+2 and CCL4 higher, whereas TRO expressed limited difference in both cell types. Stability between cycles was demonstrated for gene expression at both LH+2-more than 60% of genes had cycles for each participant permitted the aim of obtaining information on intercycle and intracycle variability to be achieved. Our results support the feasibility of a clinical means of identification of a functional receptive endometrium. The robustness of data from individual women suggests that samples from one cycle can generally be applied to subsequent cycles. Funding was granted from the Tertiary Education

  17. Metformin Use and Endometrial Cancer Survival

    Science.gov (United States)

    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

  18. The relationship of cerb B 2 expression with estrogen receptor and progesterone receptor and prognostic parameters in endometrial carcinomas

    Directory of Open Access Journals (Sweden)

    Kandemir Nilufer

    2010-02-01

    Full Text Available Abstract Background Endometrial carcinoma (EC is the most common malignancy of the female genital tract. Gene alterations and overexpression of various oncogenes are important in tumor development. The human HER 2 neu (c-erbB-2 gene product is a transmembrane receptor with an intracellular tyrosine kinase that plays an important role in coordinating the endometrial growth factor receptor signaling network. The aim of this study was to investigate the expression of c-erbB-2 in endometrial cancer, to study its correlation to established prognostic parameters and estrogen receptor (ER and progesterone receptor (PR status. Methods Immunohistochemical (IHC analyses of ER, PR and c-erbB-2 were performed in 72 EC cases. Results We detected a positive staining with c erbB 2 in 18.1% of the cases and determined a statistically significant relation between c-erbB-2 and PR. We could not find a statistically significant relation between c-erbB-2 staining and ER. There was not a statistically significant difference between c-erbB-2 and histological grade. The highest level of c-erbB-2 was found in grade 2 cases. There was not any statistically significant relation between c-erbB-2 and menstrual status, myometrial invasion, lymph node status, stage and survival. Conclusions Although our study provides additional evidence of the potential prognostic role of c-erbB-2, further prospective and controlled studies are required to validate their clinical usefulness.

  19. The correlation between endometrial thickness and outcome of in vitro fertilization and embryo transfer (IVF-ET outcome

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    Al-Rejjal Rafat

    2008-09-01

    Full Text Available Abstract Background To evaluate the relationship between endometrial thickness on day of human chorionic gonadotrophin administration (hCG and pregnancy outcome in a large number of consecutive in vitro fertilization and embryo transfer (IVF-ET cycles. Methods A retrospective cohort study including all patients who had IVF-ET from January 2003–December 2005 conducted at a tertiary center. Results A total of 2464 cycles were analysed. Pregnancy rate (PR was 35.8%. PR increased linearly (r = 0.864 from 29.4% among patients with a lining of less than or equal to 6 mm, to 44.4% among patients with a lining of greater than or equal to 17 mm. ROC showed that endometrial thickness is not a good predictor of PR, so a definite cut-off value could not be established (AUC = 0.55. Conclusion There is a positive linear relationship between the endometrial thickness measured on the day of hCG injection and PR, and is independent of other variables. Hence aiming for a thicker endometrium should be considered.

  20. Endometrial stromal sarcoma in combination with mixed type endometrial carcinomas: A case report and literature review.

    Science.gov (United States)

    Xiu, Xiao-Xin; Wang, Hua-Li; Yun-Yi, Lv; Fan-Dou, Kong; Jin-Ping, Hou

    2017-12-01

    Endometrial stromal sarcoma (ESS) is rare, representing only approximately 0.2% of all uterine malignancies. Mixed type endometrial carcinomas (MT-ECs) are rare tumors with both type I and II features, and are difficult to diagnose. Cases of ESS and MT-ECs coexisting in the same patient are extremely rare. This study aimed to describe a case of ESS in combination with MT-ECs in a 47-year-old premenopausal woman. A woman presented to the hospital complaining of occasional abdominal pain and had high tumor markers: cancer antigen (CA) 19-9 (263.6 U/mL) and CA 125 (428.0 U/mL). Transvaginal ultrasound examination revealed a complex mass (12.3 × 9.1 × 6.3 cm) with solid and cystic components on the right rear wall of the uterus. Abdominopelvic computed tomography images showed a pelvic cystic-solid mixed mass. The patient underwent an exploratory midline laparotomy. The mass was hypothesized to be malignant on the uterine posterior wall. Tumor deposits were found on bilateral parametrium. On peritoneal implantation, multiple metastases were seen on the serosal surface of the bowel and greater omentum. A frozen section revealed a spindle cell sarcoma. Pathological reports following surgery revealed concurrent ESS and MT-ECs. The patient underwent a total abdominal hysterectomy, bilateral salpingo-oophorectomy, total omentectomy, and macroscopic clearance of the tumor. Adjuvant chemotherapy was given. The patient was still alive when this report was written. Considering the rarity of ESS in combination with MT-ECs, this study presented an overview of the literature and discussed a number of histological and clinical issues. Nevertheless, etiology and pathogenesis of these tumors need further investigation.

  1. Exome-wide association study of endometrial cancer in a multiethnic population.

    Directory of Open Access Journals (Sweden)

    Maxine M Chen

    Full Text Available Endometrial cancer (EC contributes substantially to total burden of cancer morbidity and mortality in the United States. Family history is a known risk factor for EC, thus genetic factors may play a role in EC pathogenesis. Three previous genome-wide association studies (GWAS have found only one locus associated with EC, suggesting that common variants with large effects may not contribute greatly to EC risk. Alternatively, we hypothesize that rare variants may contribute to EC risk. We conducted an exome-wide association study (EXWAS of EC using the Infinium HumanExome BeadChip in order to identify rare variants associated with EC risk. We successfully genotyped 177,139 variants in a multiethnic population of 1,055 cases and 1,778 controls from four studies that were part of the Epidemiology of Endometrial Cancer Consortium (E2C2. No variants reached global significance in the study, suggesting that more power is needed to detect modest associations between rare genetic variants and risk of EC.

  2. Similar Pregnancy Rates Between Different Endometrial Echo Patterns in ART

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    Serdar Ünlü

    2008-08-01

    CONCLUSION: As the morphological assessment of endometrium by sonography has a high inter observer variability and the influence of sonographic patterns of endometrium on pregnancy rates remains unclear, we conclude that evaluating endometrial patterns by sonography alone is not an optimal diagnostic procedure for determining the success of IVF outcome.

  3. Endometrial osseous metaplasia: case report with literature review ...

    African Journals Online (AJOL)

    Endometrial osseous metaplasia is a rare pathological condition with mature bone in the endometrium and can be a cause for menorrhagia and infertility as bone in the endometrium acts like intrauterine contraceptive device. We report one such case with brief review of literature in a 28‑year‑old woman presenting with ...

  4. Role of pelvic lymphadenectomy in stage 1A endometrial carcinoma ...

    African Journals Online (AJOL)

    Introduction: Endometrial cancer is the commonest gynecological cancer mostly affecting women in the postmenopausal age group. There is a debate regarding the need of pelvic lymphadenectomy in managing stage 1A diagnosed preoperatively, we try to evaluate this need. Objective: To evaluate the role of pelvic ...

  5. Histopathological Patterns of Endometrial Lesions in Patients with ...

    African Journals Online (AJOL)

    Mubeen

    Background: Endometrial diseases ranked among the most common gynecological disorders that affect women globally. These diseases cut across all age groups and contribute significantly to increased maternal morbidity and mortality. Due to the wide range of histopathological patterns,the need for urgent diagnosis and ...

  6. Robotic-assisted laparoscopic hysterectomy for women with endometrial cancer

    DEFF Research Database (Denmark)

    Herling, Suzanne Forsyth; Møller, Ann M; Palle, Connie

    2017-01-01

    -anaesthesia care unit was shorter for patients undergoing RALH. CONCLUSIONS: RALH appears advantageous for women treated for endometrial cancer in terms of post-operative complications. We recommend the use of the Clavien-Dindo classification of surgical outcomes for quality assessment. FUNDING: departmental only...

  7. Subcutaneous metastasis from endometrial cancer; case report and literature review

    Directory of Open Access Journals (Sweden)

    Nicolae Bacalbasa

    2018-05-01

    Full Text Available Subcutaneous metastases from endometrial cancer are rare situations, only few cases being described so far. The main incriminated mechanisms leading to the apparition of such lesions include hematogenous and lymphatic spread. We present the case of a 66-year-old patient known with previous history of stage IIIA endometroid endometrial carcinoma initially treated by surgery and adjuvant chemotherapy who developed at 18 months follow-up a distant subcutaneous oligometastasis. At this time the patient was resubmitted to surgery, the lesion being successfully removed. The histopathological result confirmed the endometrial cancer origin of this lesion. Subcutaneous and cutaneous metastases from endometrial cancer are rare eventualities which are usually diagnosed as part of systemic dissemination of this malignancy; in these cases, the patient is only candidate for oncological treatment with palliative intent. In some cases, in which the lesions occur as oligometastatic disease, surgery might be performed with curative intent. In our case the diagnostic of the subcutaneous lesion as oligometastatic disease transformed the patient in a perfect candidate for curative oncological surgery.

  8. Magnetic resonance imaging of the uterus after endometrial resection

    International Nuclear Information System (INIS)

    Turnbull, L.; Jumaa, A.; Dhawan, S.; Horsman, A.; Killick, S.

    1998-01-01

    The majority of amenorrhoeic and all menstruating women have residual endometrium after endometrial resection. The lack of communication of islands of residual endometrium with the uterine cavity results in haematometra formation, fallopian tube dilatation and possibly free intraperitoneal fluid. (N.C.)

  9. Magnetic resonance imaging of the uterus after endometrial resection

    Energy Technology Data Exchange (ETDEWEB)

    Turnbull, L.; Jumaa, A.; Dhawan, S.; Horsman, A.; Killick, S

    1998-02-01

    The majority of amenorrhoeic and all menstruating women have residual endometrium after endometrial resection. The lack of communication of islands of residual endometrium with the uterine cavity results in haematometra formation, fallopian tube dilatation and possibly free intraperitoneal fluid. (N.C.)

  10. Cervicovaginal Smear Findings of Endometrial Serous Carcinoma: A Case Report

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    Figen Barut

    2008-08-01

    Although cervicovaginal smear generally is not a sensitive screening test for endometrial carcinomas, it played an important role in determining serous carcinoma. This may be related with advanced stage and/or aggressive features of the neoplastic process.

  11. Role of pelvic lymphadenectomy in stage 1A endometrial carcinoma ...

    African Journals Online (AJOL)

    Hossam Hassan Aly Hassan El Sokkary

    2013-10-31

    Oct 31, 2013 ... phadenectomy in managing stage 1A diagnosed preoperatively, we try to evaluate this need. Objective: To ... Methods: 60 Cases of endometrial carcinoma diagnosed by fractional curettage and proved to be stage 1A .... The strongest argument for routine staging is the avoidance of pelvic radiation therapy ...

  12. Post-operative treatment of endometrial carcinoma. Chapter 20

    International Nuclear Information System (INIS)

    Kuipers, Tj.; Star, W.M.

    1980-01-01

    The alternative forms of post-operative radiotherapy given in Rotterdam for endometrial carcinoma are described. Patients with infiltration involving less than half the thickness of the myometrium are treated with low dose-rate 137 Cs afterloading techniques. However, in patients with deep infiltration, a combination of high dose-rate Cathetron treatment and external irradiation is used. (U.K.)

  13. Reproducibility of measurement of myometrial invasion in endometrial carcinoma

    NARCIS (Netherlands)

    Putten, L.J.M. van der; Vijver, K. van der; Bartosch, C.; Davidson, B.; Gatius, S.; Matias-Guiu, X.; McCluggage, W.G.; Toledo, G.; Wurff, A.A. van der; Pijnenborg, J.M.A.; Massuger, L.F.A.G.; Bulten, J.

    2017-01-01

    Myometrial invasion (MI) as a percentage (%MI), categorized into <50 or >/=50 %, is an important predictor of prognosis in endometrial carcinoma. Recent studies suggest that tumor-free distance (TFD) to serosa and the absolute depth of invasion (DOI) might be stronger predictors of prognosis.

  14. Robotic-assisted laparoscopic hysterectomy for women with endometrial cancer

    DEFF Research Database (Denmark)

    Herling, Suzanne Forsyth; Møller, Ann M; Palle, Connie

    2017-01-01

    INTRODUCTION: Robotic-assisted laparoscopic hysterectomy (RALH) has become a widely used approach for women with endometrial cancer and has replaced laparotomy. It has been questioned if the increased costs are justified by superior surgical outcomes. The aim of the present study was to examine...

  15. Risk of endometrial cancer in women treated with ovary-stimulating drugs for subfertility.

    Science.gov (United States)

    Skalkidou, Alkistis; Sergentanis, Theodoros N; Gialamas, Spyros P; Georgakis, Marios K; Psaltopoulou, Theodora; Trivella, Marialena; Siristatidis, Charalampos S; Evangelou, Evangelos; Petridou, Eleni

    2017-03-25

    Medical treatment for subfertility principally involves the use of ovary-stimulating agents, including selective oestrogen receptor modulators (SERMs), such as clomiphene citrate, gonadotropins, gonadotropin-releasing hormone (GnRH) agonists and antagonists, as well as human chorionic gonadotropin. Ovary-stimulating drugs may act directly or indirectly upon the endometrium (lining of the womb). Nulliparity and some causes of subfertility are recognized as risk factors for endometrial cancer. To evaluate the association between the use of ovary-stimulating drugs for the treatment of subfertility and the risk of endometrial cancer. A search was performed in CENTRAL, MEDLINE (Ovid) and Embase (Ovid) databases up to July 2016, using a predefined search algorithm. A search in OpenGrey, ProQuest, ClinicalTrials.gov, ZETOC and reports of major conferences was also performed. We did not impose language and publication status restrictions. Cohort and case-control studies reporting on the association between endometrial cancer and exposure to ovary-stimulating drugs for subfertility in adult women were deemed eligible. Study characteristics and findings were extracted by review authors independently working in pairs. Inconsistency between studies was quantified by estimating I 2 . Random-effects (RE) models were used to calculate pooled effect estimates. Separate analyses were performed, comparing treated subfertile women versus general population and/or unexposed subfertile women, to address the superimposition of subfertility as an independent risk factor for endometrial cancer. Nineteen studies were eligible for inclusion (1,937,880 participants). Overall, the quality of evidence was very low, due to serious risk of bias and indirectness (non-randomised studies (NRS), which was reflected on the GRADE assessment.Six eligible studies, including subfertile women, without a general population control group, found that exposure to any ovary-stimulating drug was not associated

  16. MicroRNA array and microarray evaluation of endometrial receptivity in patients with high serum progesterone levels on the day of hCG administration

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    Liu Ping

    2011-03-01

    Full Text Available Abstract Background To determine the effect of higher progesterone (P level on endometrial receptivity. Methods This was a prospective analysis conducted in the Reproductive Medical Center of Peking University Third Hospital. All patients received IVF treatment and canceled embryo transfer in the same cycle and were divided into group 1 (normal P; 7 patients and group 2 (elevated P; 12 patients. Endometrial biopsies were performed 6 days after oocyte retrieval. The global miRNA and mRNA gene expressions in endometrial biopsies were investigated with a V4.0 miRNA probe and 22 K Human Genome Array. Fold ratios were derived to compare gene regulation between the groups. Spp1 and Ang gene expression was selected to verify the array results by RT-PCR and the protein expression of osteopontin and VEGF was determined using an immunohistochemical method. Results There were 4 miRNA (all down-regulated and 22 mRNA (13 up-regulated and 9 down-regulated exhibiting differential expression between the groups on the microRNA and microarray chips. miRNA-451, Spp1, and Ang expression in RT-PCR verified the array results. Osteopontin and VEGF were also shown to have positive expression in the endometrium. Conclusions Data from microRNA and microarray analysis suggests dissimilar endometrial receptivity in patients with high P levels on the day of hCG, and elevated osteopontin and decreased VEGF had poor pregnancy rates.

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

    Science.gov (United States)

    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. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  18. DJ-1 is a reliable serum biomarker for discriminating high-risk endometrial cancer.

    Science.gov (United States)

    Di Cello, Annalisa; Di Sanzo, Maddalena; Perrone, Francesca Marta; Santamaria, Gianluca; Rania, Erika; Angotti, Elvira; Venturella, Roberta; Mancuso, Serafina; Zullo, Fulvio; Cuda, Giovanni; Costanzo, Francesco

    2017-06-01

    New reliable approaches to stratify patients with endometrial cancer into risk categories are highly needed. We have recently demonstrated that DJ-1 is overexpressed in endometrial cancer, showing significantly higher levels both in serum and tissue of patients with high-risk endometrial cancer compared with low-risk endometrial cancer. In this experimental study, we further extended our observation, evaluating the role of DJ-1 as an accurate serum biomarker for high-risk endometrial cancer. A total of 101 endometrial cancer patients and 44 healthy subjects were prospectively recruited. DJ-1 serum levels were evaluated comparing cases and controls and, among endometrial cancer patients, between high- and low-risk patients. The results demonstrate that DJ-1 levels are significantly higher in cases versus controls and in high- versus low-risk patients. The receiver operating characteristic curve analysis shows that DJ-1 has a very good diagnostic accuracy in discriminating endometrial cancer patients versus controls and an excellent accuracy in distinguishing, among endometrial cancer patients, low- from high-risk cases. DJ-1 sensitivity and specificity are the highest when high- and low-risk patients are compared, reaching the value of 95% and 99%, respectively. Moreover, DJ-1 serum levels seem to be correlated with worsening of the endometrial cancer grade and histotype, making it a reliable tool in the preoperative decision-making process.

  19. Meta-analysis of bipolar radiofrequency endometrial ablation versus thermal balloon endometrial ablation for the treatment of heavy menstrual bleeding.

    Science.gov (United States)

    Zhai, Yan; Zhang, Zihan; Wang, Wei; Zheng, Tingping; Zhang, Huili

    2018-01-01

    Heavy menstrual bleeding is a common problem that can severely affect quality of life. To compare bipolar radiofrequency endometrial ablation and thermal balloon ablation for heavy menstrual bleeding in terms of efficacy and health-related quality of life (HRQoL). Online registries were systematically searched using relevant terms without language restriction from inception to November 24, 2016. Randomized control trials or cohort studies of women with heavy menstrual bleeding comparing the efficacy of two treatments were eligible. Data were extracted. Results were expressed as risk ratios (RRs) or weighted mean differences (WMDs) with 95% confidence intervals (CIs). Six studies involving 901 patients were included. Amenorrhea rate at 12 months was significantly higher after bipolar radiofrequency endometrial ablation than after thermal balloon ablation (RR 2.73, 95% CI 2.00-3.73). However, no difference at 12 months was noted for dysmenorrhea (RR 1.04, 95% CI 0.68-1.58) or treatment failure (RR 0.78, 95% CI 0.38-1.60). The only significant difference for HRQoL outcomes was for change in SAQ pleasure score (12 months: WMD -3.51, 95% CI -5.42 to -1.60). Bipolar radiofrequency endometrial ablation and thermal balloon ablation reduce menstrual loss and improve quality of life. However, bipolar radiofrequency endometrial ablation is more effective in terms of amenorrhea rate and SAQ pleasure. © 2017 International Federation of Gynecology and Obstetrics.

  20. Diet and endometrial cancer: a focus on the role of fruit and vegetable intake, Mediterranean diet and dietary inflammatory index in the endometrial cancer risk.

    Science.gov (United States)

    Ricceri, Fulvio; Giraudo, Maria Teresa; Fasanelli, Francesca; Milanese, Dario; Sciannameo, Veronica; Fiorini, Laura; Sacerdote, Carlotta

    2017-11-13

    Endometrial cancer is the fourth most common cancer in European women. The major risk factors for endometrial cancer are related to the exposure of endometrium to estrogens not opposed to progestogens, that can lead to a chronic endometrial inflammation. Diet may play a role in cancer risk by modulating chronic inflammation. In the framework of a case-control study, we recruited 297 women with newly diagnosed endometrial cancer and 307 controls from Northern Italy. Using logistic regression, we investigated the role of fruit and vegetable intake, adherence to the Mediterranean diet (MD), and the dietary inflammatory index (DII) in endometrial cancer risk. Women in the highest quintile of vegetable intake had a statistically significantly lower endometrial cancer risk (adjusted OR 5th quintile vs 1st quintile: 0.34, 95% CI 0.17-0.68). Women with high adherence to the MD had a risk of endometrial cancer that was about half that of women with low adherence to the MD (adjusted OR: 0.51, 95% CI 0.39-0.86). A protective effect was detected for all the lower quintiles of DII, with the highest protective effect seen for the lowest quintile (adjusted OR 5th quintile vs 1st quintile: 3.28, 95% CI 1.30-8.26). These results suggest that high vegetable intake, adherence to the MD, and a low DII are related to a lower endometrial cancer risk, with several putative connected biological mechanisms that strengthen the biological plausibility of this association.

  1. Endometrial Cancer Side-Population Cells Show Prominent Migration and Have a Potential to Differentiate into the Mesenchymal Cell Lineage

    Science.gov (United States)

    Kato, Kiyoko; Takao, Tomoka; Kuboyama, Ayumi; Tanaka, Yoshihiro; Ohgami, Tatsuhiro; Yamaguchi, Shinichiro; Adachi, Sawako; Yoneda, Tomoko; Ueoka, Yousuke; Kato, Keiji; Hayashi, Shinichi; Asanoma, Kazuo; Wake, Norio

    2010-01-01

    Cancer stem-like cell subpopulations, referred to as “side-population” (SP) cells, have been identified in several tumors based on their ability to efflux the fluorescent dye Hoechst 33342. Although SP cells have been identified in the normal human endometrium and endometrial cancer, little is known about their characteristics. In this study, we isolated and characterized the SP cells in human endometrial cancer cells and in rat endometrial cells expressing oncogenic human K-Ras protein. These SP cells showed i) reduction in the expression levels of differentiation markers; ii) long-term proliferative capacity of the cell cultures; iii) self-renewal capacity in vitro; iv) enhancement of migration, lamellipodia, and, uropodia formation; and v) enhanced tumorigenicity. In nude mice, SP cells formed large, invasive tumors, which were composed of both tumor cells and stromal-like cells with enriched extracellular matrix. The expression levels of vimentin, α-smooth muscle actin, and collagen III were enhanced in SP tumors compared with the levels in non-SP tumors. In addition, analysis of microdissected samples and fluorescence in situ hybridization of Hec1-SP-tumors showed that the stromal-like cells with enriched extracellular matrix contained human DNA, confirming that the stromal-like cells were derived from the inoculated cells. Moreober, in a Matrigel assay, SP cells differentiated into α-smooth muscle actin-expressing cells. These findings demonstrate that SP cells have cancer stem-like cell features, including the potential to differentiate into the mesenchymal cell lineage. PMID:20008133

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

    Science.gov (United States)

    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

  3. [Immunomorphologic features of epithelial-stromal relationships at hyperplasia and endometrial carcinoma].

    Science.gov (United States)

    Bantysh, B B; Paukov, v S; Kogan, E A

    2012-01-01

    The results of a immunomorphologic comprehensive study of epithelial-stromal relationships in the uterus hyperplasia and endometrial cancer suggest that the suppressor gene of cancer (PTEN) plays a key role in the process of neoplastic transformation of endometrial hyperplasia and adenocarcinoma development. For the first time the existence of two highly differentiated endometrial adenocarcinoma immunophenotype were detected The first one is a PTEN-negative endometrial aedenocarcinoma, characterized by an almost complete inhibition of tumor suppressor gene PTEN in the epithelium of the glands and stromal cell of the tumor The second type is a PTEN-positive endometrial adenocarcinoma, in which epithelial and stromal tumor suppressor gene PTEN activity has retained Based on these results we have formulated a hypothesis about the different types of endometrial hyperplasia morphogenesis and its possible transfer to cervical cancer associated with features of tumor suppressor gene PTEN.

  4. Sampling in Atypical Endometrial Hyperplasia: Which Method Results in the Lowest Underestimation of Endometrial Cancer? A Systematic Review and Meta-analysis.

    Science.gov (United States)

    Bourdel, Nicolas; Chauvet, Pauline; Tognazza, Enrica; Pereira, Bruno; Botchorishvili, Revaz; Canis, Michel

    2016-01-01

    Our objective was to identify the most accurate method of endometrial sampling for the diagnosis of complex atypical hyperplasia (CAH), and the related risk of underestimation of endometrial cancer. We conducted a systematic literature search in PubMed and EMBASE (January 1999-September 2013) to identify all registered articles on this subject. Studies were selected with a 2-step method. First, titles and abstracts were analyzed by 2 reviewers, and 69 relevant articles were selected for full reading. Then, the full articles were evaluated to determine whether full inclusion criteria were met. We selected 27 studies, taking into consideration the comparison between histology of endometrial hyperplasia obtained by diagnostic tests of interest (uterine curettage, hysteroscopically guided biopsy, or hysteroscopic endometrial resection) and subsequent results of hysterectomy. Analysis of the studies reviewed focused on 1106 patients with a preoperative diagnosis of atypical endometrial hyperplasia. The mean risk of finding endometrial cancer at hysterectomy after atypical endometrial hyperplasia diagnosed by uterine curettage was 32.7% (95% confidence interval [CI], 26.2-39.9), with a risk of 45.3% (95% CI, 32.8-58.5) after hysteroscopically guided biopsy and 5.8% (95% CI, 0.8-31.7) after hysteroscopic resection. In total, the risk of underestimation of endometrial cancer reaches a very high rate in patients with CAH using the classic method of evaluation (i.e., uterine curettage or hysteroscopically guided biopsy). This rate of underdiagnosed endometrial cancer leads to the risk of inappropriate surgical procedures (31.7% of tubal conservation in the data available and no abdominal exploration in 24.6% of the cases). Hysteroscopic resection seems to reduce the risk of underdiagnosed endometrial cancer. Copyright © 2016 AAGL. Published by Elsevier Inc. All rights reserved.

  5. Does Metformin affect ER, PR, IGF-1R, β-catenin and PAX-2 expression in women with diabetes mellitus and endometrial cancer?

    Science.gov (United States)

    Markowska, Anna; Pawałowska, Monika; Filas, Violetta; Korski, Konstanty; Gryboś, Marian; Sajdak, Stefan; Olejek, Anita; Bednarek, Wiesława; Spiewankiewicz, Beata; Lubin, Jolanta; Markowska, Janina

    2013-12-05

    Diabetes mellitus, as a risk factor for endometrial cancer (EC), causes an increase in insulin and IGF-1 concentrations in the blood serum. The increase in insulin and IGF-1 are considered mitogenic factors contributory to cancer development. Studies suggest that metformin has preventive activity, decreasing mortality and the risk of neoplasms. Since estrogen (ER), progesterone (PR) and IGF-1 (IGF-1R) receptor expression and β-catenin and PAX-2 mutations are significant in the development of endometrial cancer, it was decided to study these factors in patients with endometrial cancer and type 2 diabetes mellitus (DM2), and to establish the effects of metformin on their expression. The expression of ER, PR, IGF-1R, β-catenin and PAX-2 have been immunohistochemically investigated in 86 type I endometrial cancer specimens. Patients were grouped according to the presence of DM2 and the type of hypoglycemic treatment administered. Comparing EC patients with DM2 and normal glycemic status, we found increased IGF-1R expression in women with DM2. A decrease in ER expression was noted in women with EC and DM2 receiving metformin as compared to women treated with insulin (p = 0.004). There was no statistically significant difference in PR, IGF-1R, β-catenin and PAX-2 expression among women receiving metformin and other hypoglycemic treatment. Although epidemiological studies suggest the beneficial role of metformin in many human cancers, there are still few studies confirming its favorable effect on endometrial cancer. Decreased ER expression in patients receiving metformin needs further research to allow evaluation of its clinical significance.

  6. Accuracy of doppler ultrasound in diagnosis of endometrial carcinoma

    International Nuclear Information System (INIS)

    Batool, S.; Raza, S.; Manzur, S.

    2013-01-01

    Objective: To determine the accuracy of Doppler ultrasound in the diagnosis of endometrial carcinoma in patients presenting with post-menopausal bleeding while taking histopathological findings as the gold standard. Methods: The cross-sectional study was done at the Department of Radiology, Bahawal Victoria Hospital, Bahawalpur, from April 1 to September 30, 2009, and comprised 128 patients above 50 years of age having history of post-menopausal bleeding and who were referred to the department. Name, age and hospital registration number were recorded on a proforma. Doppler ultrasound was performed and endometrial thickness and uterine artery resistive index were recorded on transabdominal ultrasonography. Patients with endometrial thickness of more than 5mm and uterine artery resistive index of less than 0.7 were considered to be having endometrial carcinoma. Histopathology findings were also recorded using the hospital registration number of the patient. The findings of Doppler ultrasound scan were validated with the findings of histopathology. Results: Of the 128 patients, 48 (37.5%) were between the ages of 51 and 55 years; 46 (35.93%) were in the 56-60 age group; and 34 (26.57%) were over 65 years. On the basis of Doppler ultrasound findings, 106 (82.8%) patients were diagnosed as having endometrial carcinoma, while 22 (17.19%) were declared negative. Ultrasonography results were compared with histopathology findings. The percentages of true positive, true negative, false positive and false negative were calculated. There were 103 (80.47%) true positive; 12 (9.37%) false positive; 10 (7.81%) true negative; and 3 (2.35%) false negative. Specificity, sensitivity, positive predictive value and negative predictive value were found to be 97.16%, 76%, 89.56% and 76.92% respectively. Conclusion: The use of Doppler ultrasonography in non-invasive diagnosis of endometrial carcinoma in patients presenting with post-menopausal bleeding was quite useful with good

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

    Science.gov (United States)

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

    2015-10-01

    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.

  8. Applying the 5 Why method to verification of non-compliance causes established after application of the Ishikawa diagram in the process of improving the production of drive half-shafts

    Directory of Open Access Journals (Sweden)

    Szymon T. Dziuba

    2014-06-01

    Full Text Available The automotive industry is one of the most important branches of the global industry. For this purpose, products are produced by an extensive network of suppliers. They supply components directly to the (OEM - Original Equipment Manufacturer or to the secondary market of parts. In recent years, the economic situation in these companies has dramatically deteriorated and it is associated with a decrease in new car sales. These companies are constantly making decisions to improve their production processes using various quality tools. These actions may help to increase their competitive advantage and thereby improve their financial situation. The surveyed company produces drive half-shafts for different types of cars. The studies were carried out to analyse the causes of non-compliance - falling band from the housing on the drive shaft. In order to identify and verify the causes for non-compliance and undertake corrective action following methods were used: Ishikawa diagram, 5WHY and brainstorming.

  9. Value Of Three Dimensional Power Doppler Ultrasound In Prediction Of Endometrial Carcinoma In Patients With Postmenopausal Bleeding

    International Nuclear Information System (INIS)

    Abou-Gabal, A.; Akl, Sh.A.; Hussain, Sh.H.; Allam, H.A.

    2013-01-01

    Objective: to determine whether endometrial volume or power Doppler indices as measured by 3D ultrasound imaging can discriminate between benign and malignant endometrium in women with postmenopausal bleeding and endometrial thickness > 5 mm. Study design: Eighty-four patients with postmenopausal bleeding and endometrial thickness > 5 mm underwent 3D power Doppler ultrasound examination of the corpus uteri. The endometrial volume was calculated, along with the vascularisation index (VI), flow index and vascularisation flow index (VFI) in the endometrium. The gold standard was the histological diagnosis of the endometrium. Results: There were 56 benign and 28 malignant endometrial. Endometrial thickness and volume were significantly larger in malignant than in benign endometrial, and flow indices in the endometrium were Significantly higher. The area under the ROC curve (AUC) of endometrial thickness was 0.83, that of endometrial volume 0.73, and that of the best power Doppler variable FI 0.93. The best logistic regression model for predicting malignancy contained the variables endometrial thickness and FI. Its AUC was 0.93. Conclusion: the diagnostic performance of endometrial volume measured by 3d imaging with regard to discriminating between benign and malignant endometrium was not superior to that of endometrial thickness measured by 2D ultrasound examination, but 3D power Doppler flow indices are good diagnostic tool in predicting endometrial carcinoma

  10. Endometrial polyps and associated factors in Danish women aged 36-74 years

    DEFF Research Database (Denmark)

    Dreisler, Eva; Sorensen, Soren Stampe; Lose, Gunnar

    2008-01-01

    , the following was positively associated with endometrial polyps: current use of hormone therapy (odds ratio, 2.81; 95% CI, 1.29-6.13) and being overweight (body mass index > 25 kg/m(2)) (odds ratio, 2.06; 95% CI, 1.12-3.79) (postmenopausal women). Negatively associated was use of oral contraceptive pills (odds...... women were positively associated, whereas the use of oral contraceptive pills was negatively associated with endometrial polyps. Hypertension and cervical polyps were not associated with endometrial polyps. Endometrial polyps were infrequently related to premalignant and malignant disease....

  11. Canine Uterine Leiomyoma with Epithelial Tissue Foci, Adenomyosis, and Cystic Endometrial Hyperplasia

    Directory of Open Access Journals (Sweden)

    George S. Karagiannis

    2011-01-01

    Full Text Available An 11-year-old Labrador Retriever bitch with a history of intermittent, sanguineous vaginal discharge of a six-month duration was presented. During exploratory laparotomy, two well-delineated, intramural masses were identified bilaterally in the uterine horns. Histopathologic examination of the mass on the left horn showed that it was a typical leiomyoma. However, the second mass appeared with an unusual coexistence of histological lesions, involving epithelial tissue foci, mild focal adenomyosis, and cystic endometrial hyperplasia. Interestingly, such combination was never encountered before in dogs. Although uterine leiomyoma is quite usual in the reproductive system of female dogs, this case resembled relevant cases of human uterine adenomyomas in morphology, and thus it was offered a similar tentative diagnosis.

  12. Vabrasio is a reliable test to rule out endometrial cancer

    DEFF Research Database (Denmark)

    Andersen, Anita; Lauszus, Finn Friis

    2015-01-01

    Introduction: Endometrial cancer is the most common gynaecological cancer in Denmark, and its incidence peaks in the postmenopausal years. The aim of the present study was to evaluate the effectiveness of vacuum aspirator (vabrasio) for the detection of endometrial cancer in terms of sensitivity......, specificity and predictive value. Methods: A cohort counting 503 women who had vabrasio was evaluated retrospectively. The women included were consecutive patients who had received vabrasio at the 
Department of Gynaecology and Obstetrics at Herning Hos­pital, Denmark, during a two-year period. They were iden......­tified by searching the hospital database for the Inter­na­tional Classification of Diseases, tenth version (ICD-10) code for vabrasio.
 Results: The indications for vabrasio were postmeno­pausal bleeding (45%), meno/metrorrhagia (43%) and thickened endometrium/polyp (6%). The first evaluation by vabrasio was normal...

  13. Endometrial intraepithelial carcinoma: A case report and brief review

    Directory of Open Access Journals (Sweden)

    Ram Manisha

    2008-10-01

    Full Text Available This case report describes the precursor lesion of uterine papillary serous carcinoma (UPSC. A 65-year-old post-menopausal female presented with prolapse and vaginal discharge and underwent a hysterectomy revealing an atrophic endometrium, highly atypical endometrial glands, the lining cells of which showed pseudostratification, hobnailing, a high nuclear to cytoplasmic ratio, and prominent nucleoli. A p53 immunoreactivity score of 8 and a MIB-1 index of 80% was obtained leading to a diagnosis of endometrial intraepithelial carcinoma (EIC. Since serous EIC is commonly associated with extra-uterine serous carcinoma, it is a uniquely aggressive precursor lesion. Molecular studies support the hypothesis that EIC is a precursor of both uterine and extra-uterine invasive serous carcinomas. This is why the treatment protocol for EIC cases is total abdominal hysterectomy (TAH, accompanied by a staging procedure. In our patient, EIC was limited to the endometrium; associated with an excellent clinical outcome.

  14. A new afterloading applicator for primary brachytherapy of endometrial cancer

    International Nuclear Information System (INIS)

    Bauer, M.; Schulz-Wendtland, R.

    1993-01-01

    The authors describe and have used a new afterloading applicator in six patients for primary radiation therapy of endometrial cancer. The first introduction of the applicator was done under general anaesthesia. Dilating the cervical canal to Heger 9 made insertion easier. Prior to application it is advisable to probe the lumen of the uterine cavity with a tube or curette to estimate how far the applicator must be spread open. For brachytherapy it is advantageous to remove necrotic tumour portions. This requires experienced hands to avoid perforation of the uterus. The new afterloading applicator is easy to use, and permits direct contact between the six tubes and the tumour. In conjunction with careful planning with the help of MRI, it provides an optimal system for the treatment of endometrial cancer. (Author)

  15. Endometrial Histology of Depomedroxyprogesterone Acetate Users: A Pilot Study

    Directory of Open Access Journals (Sweden)

    2006-01-01

    Full Text Available Objective. To obtain pilot data on the endometrial histology of Depomedroxyprogesterone acetate (Depo-Provera, DMPA users experiencing breakthrough bleeding (BTB versus users with amenorrhea. To compare the endometrial histology of patients who used DMPA continuously for 3–12 months versus those who used it for 13 months or more. Methods. Cross-sectional study. Endometrial biopsy was obtained from all consenting patients who used DMPA for at least 3 months. Patients were divided into those with BTB in the last 3 months versus those with amenorrhea for at least 3 months. Histology results and duration of therapy were compared. Results. The proportion of women with chronic endometritis, uterine polyps, atrophic, proliferative, or progesterone-dominant endometrium did not differ between those DMPA users with BTB versus those with amenorrhea. Duration of therapy did not correlate with symptoms of BTB or endometrial histology. Chronic endometritis was the most common histologic finding (10/40, 25% and occurred more often in women experiencing BTB (35% versus 15% (RR 1.62 CI 0.91–2.87. Moreover, 45% of women with BTB had received DMPA for more than 12 months. Conclusions. BTB was more common than previously reported in women using DMPA for more than 12 months. Chronic endometritis, which may indicate an underlying infectious or intracavitary anatomic etiology, has not been previously reported as a frequent finding in DMPA users, and may be related to ethnic or other sociodemographic characteristics of our patient population. Further study to elucidate the etiology of chronic endometritis in these patients is warranted.

  16. A 6-year review of the outcome of endometrial ablation.

    Science.gov (United States)

    Tsaltas, J; Taylor, N; Healey, M

    1998-02-01

    In June, 1995 a postal questionnaire was distributed to all 232 women who had an endometrial ablation at Monash Medical Centre between July, 1989 and December, 1994. Data was analyzed from the 149 who responded. Length of follow-up ranged from 6 months to 6 years 6 months. Of these 78% were satisfied with their ablation and 84% found their menses to be lighter or to have stopped. The repeat ablation rate was 13% and the hysterectomy rate was 17%.

  17. Isolated splenic metastasis of endometrial adenocarcinoma--a case report.

    Science.gov (United States)

    Andrei, S; Preda, C; Andrei, A; Becheanu, G; Herlea, V; Lupescu, I; Popescu, I

    2011-01-01

    The spleen in rarely the place for solid, non-haematological tumors, isolated splenic metastases from adenocarcinomas being extremely rare findings, regardless of the origin and the histological type of the primary tumor. We present the case of a female patient with isolated splenic metastasis diagnosed by abdominal computer tomography at only 20 months after curative surgery for endometrial adenocarcinoma, in which the final diagnosis has been established by histological and immunohistochemical examination of the splenectomy piece. The haematogenous dissemination of the endometrial cancer occurs most commonly in the lungs, liver or bones, the spleen being rarely affected. In the medical literature there are cited up to date only 12 cases of solitary splenic metastasis from endometrial adenocarcinoma. The particularity of the case presented by us is the early appearance of an isolated splenic metastasis, at less than two years after curative surgery (compared to an average of 4-5 years cited in the literature), from an endometrial cancer which was classified histologicaly in the group with low-risk for relapse (well differentiated endometrioid adenocarcinoma). In conclusion, although solitary splenic secondary determinations are very rare, the incidence of the reported cases in the medical literature is increasing, their late appearance (a few years after the primary tumor's resection) and the lack of symptoms until the tumor reaches appreciable size or it complicates with necrosis, justifies the periodic abdominal imaging examination, on long-term, for postoperative monitorisation after the initial curative surgery. Their treatment of choice is open, classical splenectomy that must be followed by chemotherapy in order to prevent the development of other possible micrometastases.

  18. Hysteroscopic endometrial resection: efficacy and factors for failure

    Directory of Open Access Journals (Sweden)

    Geraldo Rodrigues de Lima

    2008-09-01

    Full Text Available Objective: To evaluate the effectiveness of hysteroscopic endometrial ablation in women with abnormal benign uterine bleeding resistant to clinical treatment, and to identify factors potentially related to its failure. Methods: Ninety patients with abnormal benign uterine bleeding were retrospectively evaluated. They were submitted to endometrial ablation between January 2000 and August 2003. Their mean age was 44.3 years and their average parity was 2.3 childbirths. All patients had been given gonadotrophin-releasing hormone analogues prior to surgery, to make the procedure easier. Rresults: After surgery, amenorrhea occurred in 20% of cases, hypomenorrhea in 30%, and eumenorrhea in 32.2%. In 17.8% of patients, the procedure failed. No intra or postoperative complications occurred. There was no statistically significant difference between the patients in which the ablation failed and those in which it was successful regarding mean age (p = 0.557, parity (p = 0.891, presence of intramural myoma (p= 0.29, submucosal myoma (p = 0.68 or endometrial polyps (p = 0.76. A significant difference between the two groups was observed with regard to the uterine size median (7  cm in the successful group and 9 cm in the failure group, p  = 0.008. A statistically significant difference was also found in follow-up time: 13 months in the first group and nine months in the second group (p = 0.001. Cconclusions: Endometrial ablation is a good treatment method for abnormal uterine bleeding of benign etiology. Special attention must be paid to patients with increased uterine size, since failure is more frequent in these cases.

  19. Smoking Decreases Endometrial Thickness in IVF/ICSI Patients.

    Science.gov (United States)

    Heger, Anna; Sator, Michael; Walch, Katharina; Pietrowski, Detlef

    2018-01-01

    Smoking is a serious problem for the health care system. Many of the compounds identified in cigarette smoke have toxic effects on the fertility of both females and males. The purpose of this study was to determine whether smoking affects clinical factors during IVF/ICSI therapy in a single-center reproductive unit. In a retrospective study of 200 IVF/ICSI cycles, endometrial thickness and the outcome of IVF/ICSI therapy were analyzed. Endometrial thickness was significantly lower in smoking patients than in non-smoking patients (10.4 ± 1.5 mm vs. 11.6 ± 1.8 mm). Age was significantly higher in women who failed to conceive. The total dose of gonadotropins administered was significantly lower in pregnant patients and the highest pregnancy rate was achieved with an rFSH protocol. BMI and number of cigarettes smoked did not influence treatment outcomes in this study. We showed that smoking has a negative effect on endometrial thickness on the day of embryo transfer. This may help to further explain the detrimental influence of tobacco smoke on implantation and pregnancy rates during assisted reproduction therapy.

  20. Acute toxicity of postoperative IMRT and chemotherapy for endometrial cancer

    International Nuclear Information System (INIS)

    Tierney, R.M.; Powell, M.A.; Mutch, D.G.; Gibb, R.K.; Rader, J.S.; Grigsby, P.W.

    2007-01-01

    The aim of this study was to determine the acute toxicity of postoperative intensity-modulated radiotherapy (IMRT) with and without chemotherapy in patients with endometrial cancer. A total of 19 patients with stages IB-IVB endometrial cancer who underwent surgery and postoperative IMRT were reviewed. The treatment planning goal was to cover the tissue at risk and minimize the dose to the bladder, bowel, and bone marrow. Median dose was 50.4 Gy (range 49.6-51.2 Gy). Altogether, 14 patients underwent chemotherapy; most were given carboplatin and paclitaxel. Toxicity was scored according to the Common Terminology Criteria for Adverse Events version 3.0 (CTCAE). The prescribed radiation treatment was completed in all patients. The prescribed cycles of chemotherapy were completed in all 14 patients, except one who received five of six cycles limited by prolonged thrombocytopenia. Chemotherapy was delayed in two patients (14%). Three patients required growth factor support during chemotherapy, and one patient required a blood transfusion. Acute grades 3-4 hematological toxicity occurred in 9 of the 14 patients (64%) who underwent chemotherapy. None experienced acute grade 3 or 4 genitourinary or gastrointestinal toxicity. Adjuvant IMRT and chemotherapy following surgery in patients with endometrial cancer is well tolerated and did not lead to treatment modification in most patients. (author)

  1. The role of adhesive molecules in endometrial cancer: part II

    Directory of Open Access Journals (Sweden)

    Andrzej Malinowski

    2010-12-01

    Full Text Available The carcinogenesis is a result of both functional and structural disorders in the tissue. It initiates as a mutationin a gene encoding protein that is essential for cellular function. The subsequent cascade of eventsleads to accumulation of mutations and loss of cellular function. The cell loses its tissue-specific morphology,disconnects from other cells and extracellular matrix and migrates – the invasion begins. It is now clear thatadhesive molecules are a key player in this cascade. These proteins of the cell membrane surface are responsiblefor attachment of the cells to each other and to the extracellular matrix. These interactions are crucial forboth structural and functional tissue organization. Lack of this homeostasis destroys the tissue architectureand impairs its function and results in invasion. Abnormal expression of adhesive molecules was reported in allexamined cancers, including endometrial cancer.Endometrial cancer is the most common gynaecological cancer in developed countries. Although in many casesdiagnosed and treated in early stages, and thus with good results, some patients cannot be cured. Completeknowledge of the pathogenesis of the disease will be helpful in identifying the patients with negative prognosticfactors, increased risk of recurrence and, perhaps, to find other therapeutic options. In the paper we are trying tosum up the up-to-date knowledge of the role of adhesive molecules in pathogenesis of endometrial cancer.

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

    Science.gov (United States)

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

    2000-02-01

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

  3. The value of diagnostic hysteroscopy with biopsy in the preoperative of endometrial ablation

    Directory of Open Access Journals (Sweden)

    Salete Yatabe

    2011-12-01

    Full Text Available Objective: To assess the value of diagnostic hysteroscopy with biopsy in the preoperative preparation for endometrial ablation. Methods: It was a prospective non-randomized study conducted at the division of Gynecologic Endoscopy of Hospital do Servidor Público Estadual “Francisco Morato de Oliveira” from March 2007 to May 2009. A total of 45 patients with abnormal uterine bleeding, and referred to endometrial ablation were included. All women underwent a diagnostic hysteroscopy, and were treated with a GnRH analogous – goserelin – 10.8 mg before surgery. The endometrial ablation was performed with a surgical resectoscope. Patients were submitted to one directed endometrial biopsy, one guided endometrial biopsy with Novak curette, and to endometrial ablation, which was considered as reference for pathological examination with samples from the biopsies. Data were analyze using the SPSS-v16 software, and considered significance at p = 0.05. Results: The mean age of women was 44.20 years (33-56, parity of 2.67 (0-9, uterus size of 139.99 calculated in cc (42-278, and the mean duration of symptoms was 3.68 years (0.5-15. The guided endometrial biopsy showed sensitivity of 80% for endometrium without atypia, and the directed endometrial biopsy had sensitivity of 60%. For proliferative endometrium the directed endometrial biopsy showed sensitivity of 76 and 100% for secretory endometrium, which was higher than the guided endometrial biopsy with 53 and 50%, respectively. Conclusion: The directed biopsy before endometrial ablation had lower sensitivity than guided biopsy for endometrium without atypia, however it was higher for proliferative and secretory endometrium.

  4. Maternal obesogenic diet induces endometrial hyperplasia, an early hallmark of endometrial cancer, in a diethylstilbestrol mouse model.

    Science.gov (United States)

    Owuor, Theresa O; Reid, Michaela; Reschke, Lauren; Hagemann, Ian; Greco, Suellen; Modi, Zeel; Moley, Kelle H

    2018-01-01

    Thirty-eight percent of US adult women are obese, meaning that more children are now born of overweight and obese mothers, leading to an increase in predisposition to several adult onset diseases. To explore this phenomenon, we developed a maternal obesity animal model by feeding mice a diet composed of high fat/ high sugar (HF/HS) and assessed both maternal diet and offspring diet on the development of endometrial cancer (ECa). We show that maternal diet by itself did not lead to ECa initiation in wildtype offspring of the C57Bl/6J mouse strain. While offspring fed a HF/HS post-weaning diet resulted in poor metabolic health and decreased uterine weight (regardless of maternal diet), it did not lead to ECa. We also investigated the effects of the maternal obesogenic diet on ECa development in a Diethylstilbestrol (DES) carcinogenesis mouse model. All mice injected with DES had reproductive tract lesions including decreased number of glands, condensed and hyalinized endometrial stroma, and fibrosis and increased collagen deposition that in some mice extended into the myometrium resulting in extensive disruption and loss of the inner and outer muscular layers. Fifty percent of DES mice that were exposed to maternal HF/HS diet developed several features indicative of the initial stages of carcinogenesis including focal glandular and atypical endometrial hyperplasia versus 0% of their Chow counterparts. There was an increase in phospho-Akt expression in DES mice exposed to maternal HF/HS diet, a regulator of persistent proliferation in the endometrium, and no difference in total Akt, phospho-PTEN and total PTEN expression. In summary, maternal HF/HS diet exposure induces endometrial hyperplasia and other precancerous phenotypes in mice treated with DES. This study suggests that maternal obesity alone is not sufficient for the development of ECa, but has an additive effect in the presence of a secondary insult such as DES.

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  8. File list: NoD.Utr.20.AllAg.Endometrial_stromal_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Utr.20.AllAg.Endometrial_stromal_cells hg19 No description Uterus Endometrial s...tromal cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/NoD.Utr.20.AllAg.Endometrial_stromal_cells.bed ...

  9. L1CAM Expression is Related to Non-Endometrioid Histology, and Prognostic for Poor Outcome in Endometrioid Endometrial Carcinoma

    NARCIS (Netherlands)

    Geels, Y.P.; Pijnenborg, J.M.A.; Gordon, B.B.; Fogel, M.; Altevogt, P.; Masadah, R.; Bulten, J.; Kempen, L.C. van; Massuger, L.F.A.G.

    2016-01-01

    The majority of endometrial carcinomas are classified as Type I endometrioid endometrial carcinomas (EECs) and have a good prognosis. Type II non-endometrioid endometrial carcinomas (NEECs) have a significant worse outcome. Yet, 20 % of the EECs are associated with an unexplained poor outcome. The

  10. Gonadotropin-releasing hormone type II (GnRH-II) agonist regulates the invasiveness of endometrial cancer cells through the GnRH-I receptor and mitogen-activated protein kinase (MAPK)-dependent activation of matrix metalloproteinase (MMP)-2

    International Nuclear Information System (INIS)

    Wu, Hsien-Ming; Wang, Hsin-Shih; Huang, Hong-Yuan; Lai, Chyong-Huey; Lee, Chyi-Long; Soong, Yung-Kuei; Leung, Peter CK

    2013-01-01

    More than 25% of patients diagnosed with endometrial carcinoma have an invasive primary cancer accompanied by metastases. Gonadotropin-releasing hormone (GnRH) plays an important role in reproduction. In mammals, expression of GnRH-II is higher than GnRH-I in reproductive tissues. Here, we examined the effect of a GnRH-II agonist on the motility of endometrial cancer cells and its mechanism of action in endometrial cancer therapy. Immunoblotting and immunohistochemistry (IHC) were used to determine the expression of the GnRH-I receptor protein in human endometrial cancer. The activity of MMP-2 in the conditioned medium was determined by gelatin zymography. Cell motility was assessed by invasion and migration assay. GnRH-I receptor si-RNA was applied to knockdown GnRH-I receptor. The GnRH-I receptor was expressed in the endometrial cancer cells. The GnRH-II agonist promoted cell motility in a dose-dependent manner. The GnRH-II agonist induced the phosphorylation of ERK1/2 and JNK, and the phosphorylation was abolished by ERK1/2 inhibitor (U0126) and the JNK inhibitor (SP600125). Cell motility promoted by GnRH-II agonist was suppressed in cells that were pretreated with U0126 and SP600125. Moreover, U0126 and SP600125 abolished the GnRH-II agonist-induced activation of MMP-2. The inhibition of MMP-2 with MMP-2 inhibitor (OA-Hy) suppressed the increase in cell motility in response to the GnRH-II agonist. Enhanced cell motility mediated by GnRH-II agonist was also suppressed by the knockdown of the endogenous GnRH-I receptor using siRNA. Our study indicates that GnRH-II agonist promoted cell motility of endometrial cancer cells through the GnRH-I receptor via the phosphorylation of ERK1/2 and JNK, and the subsequent, MAPK-dependent activation of MMP-2. Our findings represent a new concept regarding the mechanism of GnRH-II-induced cell motility in endometrial cancer cells and suggest the possibility of exploring GnRH-II as a potential therapeutic target for the

  11. Effect of Undiagnosed Deep Adenomyosis After Failed NovaSure Endometrial Ablation

    NARCIS (Netherlands)

    Mengerink, B.B.; Wurff, A.A. van der; Haar, J.F. ter; Rooij, I.A.L.M. van; Pijnenborg, J.M.

    2015-01-01

    STUDY OBJECTIVE: To determine the prevalence of adenomyosis and deep adenomyosis after NovaSure (Hologic Inc., Newark, DE) endometrial ablation in hysterectomy specimens after NovaSure endometrial ablation failure. DESIGN: Prospective observational study (Canadian Task Force classification II-2).

  12. Endometrial safety of ultra-low-dose Vagifem 10 microg in postmenopausal women with vaginal atrophy

    DEFF Research Database (Denmark)

    Ulrich, L S G; Naessen, T; Elia, D

    2010-01-01

    The objective of the study was to evaluate the endometrial safety of a 10 microg estradiol vaginal tablet in the treatment of vaginal atrophy in postmenopausal women.......The objective of the study was to evaluate the endometrial safety of a 10 microg estradiol vaginal tablet in the treatment of vaginal atrophy in postmenopausal women....

  13. Childhood body mass index and height and risk of histologic subtypes of endometrial cancer

    DEFF Research Database (Denmark)

    Aarestrup, J.; Gamborg, M.; Ulrich, L. G.

    2016-01-01

    BACKGROUND: Endometrial cancer risk factors include adult obesity and taller stature, but the influence of size earlier in life is incompletely understood. We examined whether childhood body mass index (BMI; kg m(-2)) and height were associated with histologic subtypes of endometrial cancer...

  14. Effect of demographic factors on brachytherapy treatment results in patients with endometrial cancer 1995-2010.

    Science.gov (United States)

    Jurczyk, Mieczysława U; Chmaj-Wierzchowska, Karolina; Klofik, Joanna; Sajdak, Stefan; Opala, Tomasz

    2013-01-01

    Approximately 1 in 20 female cancers in Europe is of the endometrium. Endometrial carcinoma is the most common gynaecologic cancer. Considering the fact that an upward tendency has recently been observed in morbidity due to this type of cancer, this is a serious medical problem. The presented report describes the results of the analysis of selected demographic factors and their effect on the incidence of endometrial cancer. Analysis of the results of treatment of endometrial cancer during 1995-2010 was also an objective of the study. Based on medical records obtained from the HDR Laboratory of Brachytherapy at the Gynaecological & Obstetrics Clinical Hospital, University of Medical Sciences in Poznań, the results of treatment of patients with endometrial cancer by brachytherapy were analyzed. The analysis covered a group of 400 patients. More than a half of the patients completed their education on the level of elementary or secondary school. Taking into consideration the weight of the patients, it appeared that most women had excessive body weight. Most frequently, concomitant hypertension was observed. Moreover, the age at menarche was 12 and 13. Demographic factors exert a significant effect on the incidence of endometrial cancer. 1. Overweight and obesity are important risk factors of endometrial cancer. 2. A strong relationship is observed between the occurrence of hypertension or diabetes, and the development of endometrial cancer. 3. Women who come from the rural environment and continue to live in this environment are more likely to contract endometrial cancer.

  15. New diagnostic reporting format for endometrial cytology based on cytoarchitectural criteria

    Science.gov (United States)

    Yanoh, K; Norimatsu, Y; Hirai, Y; Takeshima, N; Kamimori, A; Nakamura, Y; Shimizu, K; Kobayashi, T K; Murata, T; Shiraishi, T

    2009-01-01

    Objective: The aim of this study was to develop a new reporting format for endometrial cytology that would standardize the diagnostic criteria and the terminology used for reporting. Methods: In previous studies, cytoarchitectural criteria were found to be useful for the cytological assessment of endometrial lesions. To apply these criteria, an appropriate cytological specimen is imperative. In this article, the requirements of an adequate endometrial cytological specimen for the new diagnostic criteria are first discussed. Then, the diagnostic criteria, standardized on a combination of conventional and cytoarchitectural criteria, are presented. Third, terminology that could be used, not only for reporting the histopathological diagnosis, but also for providing better guidance for the gynaecologist to determine further clinical action, is introduced. The proposed reporting format was investigated using endometrial cytology of 58 cases that were cytologically underestimated or overestimated compared to the histopathological diagnosis made on the subsequent endometrial biopsy or surgical specimens. Results: Of the 58 cases, 12 were reassessed as being unsatisfactory for evaluation. Among the remaining 46 cases, 25 of the 27 cases, which had been underestimated and subsequently diagnosed as having endometrial carcinoma or a precursor stage on histopathological examination,were reassessed as recommended for endometrial biopsy. On the other hand, 19 cases overestimated by cytology were all reassessed as not requiring biopsy. Conclusions: The reporting format for endometrial cytology proposed in this article may improve diagnostic accuracy and reduce the number of patients managed inappropriately. PMID:18657157

  16. FIFTEEN-YEAR RADIOTHERAPY OUTCOMES OF THE RANDOMIZED PORTEC-1 TRIAL FOR ENDOMETRIAL CARCINOMA

    NARCIS (Netherlands)

    Creutzberg, Carien L.; Nout, Remi A.; Lybeert, Marnix L. M.; Warlam-Rodenhuis, Carla C.; Jobsen, Jan J.; Mens, Jan-Willem M.; Lutgens, Ludy C. H. W.; Pras, Elisabeth; van de Poll-Franse, Lonneke V.; van Putten, Wim L. J.

    2011-01-01

    Purpose: To evaluate the very long-term results of the randomized Post Operative Radiation Therapy in Endometrial Carcinoma (PORTEC)-1 trial for patients with Stage I endometrial carcinoma (EC), focusing on the role of prognostic factors for treatment selection and the long-term risk of second

  17. Awareness of endometrial cancer risk and compliance with screening in hereditary nonpolyposis colorectal cancer

    DEFF Research Database (Denmark)

    Ketabi, Zohreh; Mosgaard, Berit J; Gerdes, Anne-Marie

    2012-01-01

    Women with hereditary nonpolyposis colorectal cancer (HNPCC) have a 40-60% lifetime risk for endometrial cancer. Guidelines in Denmark recommend gynecologic screening for female members of families with HNPCC. We estimated the knowledge of endometrial cancer risk and identified possible predictors...

  18. Survival after relapse in patients with endometrial cancer : results from a randomized trial

    NARCIS (Netherlands)

    Creutzberg, CL; van Putten, WLJ; Koper, PC; Lybeert, MLM; Jobsen, JJ; Warlam-Rodenhuis, CC; De Winter, KAJ; Lutgens, LCHW; van den Bergh, ACM; van der Steen-Banasik, E; Beerman, H; van Lent, M

    Objective. The aim of this study was to determine the rates of local control and survival after relapse in patients with stage I endometrial cancer treated in the multicenter randomized PORTEC trial. Methods, The PORTEC trial included 715 patients with stage I endometrial cancer, either grade I or 2

  19. COMPARATIVE STUDY OF ENDOMETRIAL SAMPLING USING PIPELLE WITH HYSTEROSCOPIC-GUIDED BIOPSY

    Directory of Open Access Journals (Sweden)

    Nalina S

    2017-07-01

    Full Text Available BACKGROUND Hysteroscopic-guided biopsy is the gold standard for endometrial sampling, but it carries risk of general anaesthesia, infection and perforation, whereas Pipelle does not require anaesthesia or cervical dilatation and it allows outpatient and painless endometrial sampling. The aim of the study is to determine the reliability and accuracy of Pipelle aspiration in acquiring an adequate and representative endometrial sample and to compare its histopathology with hysteroscopic-directed biopsy. MATERIALS AND METHODS A prospective observational comparative study evaluating the role of Pipelle aspiration as an outpatient procedure in endometrial sampling of perimenopausal women with AUB. 150 perimenopausal women with clinical diagnosis of abnormal uterine bleeding were selected from the Gynaecology OPD of IOG, Chennai, between October 2014 and September 2015. They were subjected to endometrial sampling by Pipelle followed by hysteroscopic-directed biopsy. The efficacy of Pipelle was determined by correlating the histopathological results obtained from it and the hysteroscopic-directed biopsy. RESULTS The histopathology of the endometrium obtained using Pipelle’s curette showed a sensitivity of 93%, specificity of 90% in the detection of abnormal findings with PPV of 88% and NPV of 94%. However, accuracy of Pipelle is found to be less in the diagnosis of polyps and submucous fibroids with accuracy of nearing 100% when using hysteroscopy. CONCLUSION Pipelle endometrial sampling is convenient, easy, painless and safe in obtaining an adequate sample for histopathology with high sensitivity and specificity for endometrial pathologies and endometrial carcinoma.

  20. Transcervical Intrauterine Levobupivacaine or Lidocaine Infusion for Pain Control during Endometrial Biopsy

    Directory of Open Access Journals (Sweden)

    Nermin Kosus

    2014-01-01

    Full Text Available BACKGROUND: Endometrial biopsy is a common procedure for the investigation of many gynecological disorders including abnormal uterine bleeding, postmenopausal bleeding, abnormal cytology and infertility. Most women experience some degree of discomfort and pain during the procedure. Pain may occur during dilation of the cervix for insertion of the catheter and during endometrial biopsy, which further aggravates pain by inducing uterine contraction.

  1. Thicker endometrial linings are associated with better IVF outcomes: a cohort of 6331 women.

    Science.gov (United States)

    Holden, Emily C; Dodge, Laura E; Sneeringer, Rita; Moragianni, Vasiliki A; Penzias, Alan S; Hacker, Michele R

    2017-06-18

    Our objective was to determine if a correlation exists between endometrial thickness measured on the day of ovulation trigger during an in vitro fertilization (IVF) cycle and pregnancy outcomes among non-cancelled cycles. We performed a retrospective cohort study looking at 6331 women undergoing their first, fresh autologous IVF cycle from 1 May 2004 to 31 December 2012 at Boston IVF (Waltham, MA). Our primary outcome was the risk ratio (RR) of live birth and positive β-hCG. We found that thicker endometrial linings were associated with positive β-hCG and live birth rates. For each additional millimetre of endometrial thickness, we found a statistically significant increased risk of positive β-hCG (adjusted RR: 1.14; 95% CI: 1.09-1.18) and live birth (RR: 1.08; 95% CI: 1.05-1.11). There was no association between endometrial thickness and miscarriage (RR: 0.99; 95% CI: 0.91-1.07). Similar results were seen when categorizing endometrial thickness. Compared with an endometrial thickness >7 to <11 mm, the likelihood of a live birth was significantly higher for an endometrial thickness ≥11 mm (adjusted RR: 1.23; 95% CI: 1.11-1.37) and significantly lower for the ≤7 mm group (adjusted RR: 0.64; 95% CI: 0.45-0.90). In conclusion, thicker endometrial linings were associated with increased pregnancy and live birth rates.

  2. The importance of family history in young patients with endometrial cancer

    NARCIS (Netherlands)

    Berends, MJW; Kleibeuker, JH; de Vries, EGE; Mourits, MJE; Hollema, H; Pras, E; van der Zee, AGJ

    Endometrial cancer occurs primarily in postmenopausal women older than 60 years of age. Especially in young patients with endometrial cancer, a positive family history with respect to cancer and/or development of synchronous or metachronous tumors can be indicative of hereditary factors. One generic

  3. Decreased endometrial vascularity and receptivity in unexplained recurrent miscarriage patients during midluteal and early pregnancy phases

    Directory of Open Access Journals (Sweden)

    Shu-Yin Tan

    2015-10-01

    Conclusion: The 3D-power Doppler ultrasound is a more comprehensive and sensitive method for evaluating endometrial receptivity. Endometrial volume, VI, FI, and VFI in the midluteal phase, as well as VI in early pregnancy, can be considered as predictive factors for recurrent miscarriage.

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

    Science.gov (United States)

    Gao, Yang; Li, Shu; Li, Qinglei

    2014-08-01

    In the uterus, epithelial cell proliferation changes during the estrous cycle and pregnancy. Uncontrolled epithelial cell proliferation results in implantation failure and/or cancer development. Transforming growth factor-β (TGF-β) signaling is a fundamental regulator of diverse biological processes and is indispensable for multiple reproductive functions. However, the in vivo role of TGF-β signaling in uterine epithelial cells remains poorly defined. We have shown that in the uterus, conditional deletion of the Type 1 receptor for TGF-β (Tgfbr1) using anti-Müllerian hormone receptor type 2 (Amhr2) Cre leads to myometrial defects. Here, we describe enhanced epithelial cell proliferation by immunostaining of Ki67 in the uteri of these mice. The aberration culminated in endometrial hyperplasia in aged females. To exclude the potential influence of ovarian steroid hormones, the proliferative status of uterine epithelial cells was assessed following ovariectomy. Increased uterine epithelial cell proliferation was also revealed in ovariectomized Tgfbr1 Amhr2-Cre conditional knockout mice. We further demonstrated that transcript levels for fibroblast growth factor 10 (Fgf10) were markedly up-regulated in Tgfbr1 Amhr2-Cre conditional knockout uteri. Consistently, treatment of primary uterine stromal cells with TGF-β1 significantly reduced Fgf10 mRNA expression. Thus, our findings suggest a potential involvement of TGFBR1-mediated signaling in the regulation of uterine epithelial cell proliferation, and provide genetic evidence supporting the role of uterine epithelial cell proliferation in the pathogenesis of endometrial hyperplasia. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  5. Endometrial stromal cell attachment and matrix homeostasis in abdominal wall endometriomas.

    Science.gov (United States)

    Itoh, Hiroko; Mogami, Haruta; Bou Nemer, Laurice; Word, Larry; Rogers, David; Miller, Rodney; Word, R Ann

    2018-02-01

    How does progesterone alter matrix remodeling in abdominal wall endometriomas compared with normal endometrium? Progesterone may prevent attachment of endometrial cells to the abdominal wall, but does not ameliorate abnormal stromal cell responses of abdominal wall endometriomas. Menstruation is a tightly orchestrated physiologic event in which steroid hormones and inflammatory cells cooperatively initiate shedding of the endometrium. Abdominal wall endometriomas represent a unique form of endometriosis in which endometrial cells inoculate fascia or dermis at the time of obstetrical or gynecologic surgery. Invasion of endometrium into ectopic sites requires matrix metalloproteinases (MMPs) for tissue remodeling but endometrium is not shed externally. Observational study in 14 cases and 19 controls. Tissues and stromal cells isolated from 14 abdominal wall endometriomas were compared with 19 normal cycling endometrium using immunohistochemistry, quantitative PCR, gelatin zymography and cell attachment assays. P values cell preps to provide scientific rigor to the conclusions. The results indicate that MMP2 and MMP9 are not increased by TGFβ1 in endometrioma stromal cells. Although progesterone prevents attachment of endometrioma cells to matrix components of the abdominal wall, it does not ameliorate these abnormal stromal cell responses to TGFβ1. N/A. Endometriomas were collected from women identified pre-operatively. Not all endometriomas were collected. Stromal cells from normal endometrium were from different patients, not women undergoing endometrioma resection. This work provides insight into the mechanisms by which progesterone may prevent abdominal wall endometriomas but, once established, are refractory to progesterone treatment. Tissue acquisition was supported by NIH P01HD087150. Authors have no competing interests. © The Author(s) 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All

  6. Role of DNA methylation and epigenetic silencing of HAND2 in endometrial cancer development.

    Directory of Open Access Journals (Sweden)

    Allison Jones

    2013-11-01

    Full Text Available Endometrial cancer incidence is continuing to rise in the wake of the current ageing and obesity epidemics. Much of the risk for endometrial cancer development is influenced by the environment and lifestyle. Accumulating evidence suggests that the epigenome serves as the interface between the genome and the environment and that hypermethylation of stem cell polycomb group target genes is an epigenetic hallmark of cancer. The objective of this study was to determine the functional role of epigenetic factors in endometrial cancer development.Epigenome-wide methylation analysis of >27,000 CpG sites in endometrial cancer tissue samples (n = 64 and control samples (n = 23 revealed that HAND2 (a gene encoding a transcription factor expressed in the endometrial stroma is one of the most commonly hypermethylated and silenced genes in endometrial cancer. A novel integrative epigenome-transcriptome-interactome analysis further revealed that HAND2 is the hub of the most highly ranked differential methylation hotspot in endometrial cancer. These findings were validated using candidate gene methylation analysis in multiple clinical sample sets of tissue samples from a total of 272 additional women. Increased HAND2 methylation was a feature of premalignant endometrial lesions and was seen to parallel a decrease in RNA and protein levels. Furthermore, women with high endometrial HAND2 methylation in their premalignant lesions were less likely to respond to progesterone treatment. HAND2 methylation analysis of endometrial secretions collected using high vaginal swabs taken from women with postmenopausal bleeding specifically identified those patients with early stage endometrial cancer with both high sensitivity and high specificity (receiver operating characteristics area under the curve = 0.91 for stage 1A and 0.97 for higher than stage 1A. Finally, mice harbouring a Hand2 knock-out specifically in their endometrium were shown to develop

  7. Endometrial thickness as a predictor of the reproductive outcomes in fresh and frozen embryo transfer cycles

    Science.gov (United States)

    Zhang, Tao; Li, Zhou; Ren, Xinling; Huang, Bo; Zhu, Guijin; Yang, Wei; Jin, Lei

    2018-01-01

    Abstract To evaluate the relationship between endometrial thickness during fresh in vitro fertilization (IVF) cycles and the clinical outcomes of subsequent frozen embryo transfer (FET) cycles. FET cycles using at least one morphological good-quality blastocyst conducted between 2012 and 2013 at a university-based reproductive center were reviewed retrospectively. Endometrial ultrasonographic characteristics were recorded both on the oocyte retrieval day and on the day of progesterone supplementation in FET cycles. Clinical pregnancy rate, spontaneous abortion rate, and live birth rate were analyzed. One thousand five hundred twelve FET cycles was included. The results showed that significant difference in endometrial thickness on day of oocyte retrieval (P = .03) was observed between the live birth group (n = 844) and no live birth group (n = 668), while no significant difference in FET endometrial thickness was found (P = .261) between the live birth group and no live birth group. For endometrial thickness on oocyte retrieval day, clinical pregnancy rate ranged from 50.0% among patients with an endometrial thickness of ≤6 mm to 84.2% among patients with an endometrial thickness of >16 mm, with live birth rate from 33.3% to 63.2%. Multiple logistic regression analysis of factors related to live birth indicated endometrial thickness on oocyte retrieval day was associated with improved live birth rate (OR was 1.069, 95% CI: 1.011–1.130, P = .019), while FET endometrial thickness did not contribute significantly to pregnancy outcomes following FET cycles. The ROC curves revealed the cut-off points of endometrial thickness on oocyte retrieval day was 8.75 mm for live birth. Endometrial thickness during fresh IVF cycles was a better predictor of endometrial receptivity in subsequent FET cycles than FET cycle endometrial thickness. For those females with thin endometrium in fresh cycles, additional estradiol stimulation might be helpful for

  8. Hypoxia and hypoxia inducible factor-1α are required for normal endometrial repair during menstruation.

    Science.gov (United States)

    Maybin, Jacqueline A; Murray, Alison A; Saunders, Philippa T K; Hirani, Nikhil; Carmeliet, Peter; Critchley, Hilary O D

    2018-01-23

    Heavy menstrual bleeding (HMB) is common and debilitating, and often requires surgery due to hormonal side effects from medical therapies. Here we show that transient, physiological hypoxia occurs in the menstrual endometrium to stabilise hypoxia inducible factor 1 (HIF-1) and drive repair of the denuded surface. We report that women with HMB have decreased endometrial HIF-1α during menstruation and prolonged menstrual bleeding. In a mouse model of simulated menses, physiological endometrial hypoxia occurs during bleeding. Maintenance of mice under hyperoxia during menses decreases HIF-1α induction and delays endometrial repair. The same effects are observed upon genetic or pharmacological reduction of endometrial HIF-1α. Conversely, artificial induction of hypoxia by pharmacological stabilisation of HIF-1α rescues the delayed endometrial repair in hypoxia-deficient mice. These data reveal a role for HIF-1 in the endometrium and suggest its pharmacological stabilisation during menses offers an effective, non-hormonal treatment for women with HMB.

  9. Endometrial cancer - reduce to the minimum. A new paradigm for adjuvant treatments?

    International Nuclear Information System (INIS)

    Scheithauer, Heike R; Schulz, Diana S; Belka, Claus

    2011-01-01

    Up to now, the role of adjuvant radiation therapy and the extent of lymph node dissection for early stage endometrial cancer are controversial. In order to clarify the current position of the given adjuvant treatment options, a systematic review was performed. Both, Pubmed and ISI Web of Knowledge database were searched using the following keywords and MESH headings: 'Endometrial cancer', 'Endometrial Neoplasms', 'Endometrial Neoplasms/radiotherapy', 'External beam radiation therapy', 'Brachytherapy' and adequate combinations. Recent data from randomized trials indicate that external beam radiation therapy - particularly in combination with extended lymph node dissection - or radical lymph node dissection increases toxicity without any improvement of overall survival rates. Thus, reduced surgical aggressiveness and limitation of radiotherapy to vaginal-vault-brachytherapy only is sufficient for most cases of early stage endometrial cancer

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

    Science.gov (United States)

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

    2012-04-01

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

  11. Endometrial biomarkers for the non-invasive diagnosis of endometriosis.

    Science.gov (United States)

    Gupta, Devashana; Hull, M Louise; Fraser, Ian; Miller, Laura; Bossuyt, Patrick M M; Johnson, Neil; Nisenblat, Vicki

    2016-04-20

    About 10% of reproductive-aged women suffer from endometriosis, which is a costly, chronic disease that causes pelvic pain and subfertility. Laparoscopy is the gold standard diagnostic test for endometriosis, but it is expensive and carries surgical risks. Currently, there are no non-invasive tests available in clinical practice that accurately diagnose endometriosis. This is the first diagnostic test accuracy review of endometrial biomarkers for endometriosis that utilises Cochrane methodologies, providing an update on the rapidly expanding literature in this field. To determine the diagnostic accuracy of the endometrial biomarkers for pelvic endometriosis, using a surgical diagnosis as the reference standard. We evaluated the tests as replacement tests for diagnostic surgery and as triage tests to inform decisions to undertake surgery for endometriosis. We did not restrict the searches to particular study designs, language or publication dates. To identify trials, we searched the following databases: CENTRAL (2015, July), MEDLINE (inception to May 2015), EMBASE (inception to May 2015), CINAHL (inception to April 2015), PsycINFO (inception to April 2015), Web of Science (inception to April 2015), LILACS (inception to April 2015), OAIster (inception to April 2015), TRIP (inception to April 2015) and ClinicalTrials.gov (inception to April 2015). We searched DARE and PubMed databases up to April 2015 to identify reviews and guidelines as sources of references to potentially relevant studies. We also performed searches for papers recently published and not yet indexed in the major databases. The search strategies incorporated words in the title, abstract, text words across the record and the medical subject headings (MeSH). We considered published peer-reviewed, randomised controlled or cross-sectional studies of any size that included prospectively collected samples from any population of reproductive-aged women suspected of having one or more of the following target

  12. International Endometrial Tumor Analysis (IETA) terminology in women with postmenopausal bleeding and sonographic endometrial thickness ≥ 4.5 mm: agreement and reliability study.

    Science.gov (United States)

    Sladkevicius, P; Installé, A; Van Den Bosch, T; Timmerman, D; Benacerraf, B; Jokubkiene, L; Di Legge, A; Votino, A; Zannoni, L; De Moor, B; De Cock, B; Van Calster, B; Valentin, L

    2018-02-01

    To estimate intra- and interrater agreement and reliability with regard to describing ultrasound images of the endometrium using the International Endometrial Tumor Analysis (IETA) terminology. Four expert and four non-expert raters assessed videoclips of transvaginal ultrasound examinations of the endometrium obtained from 99 women with postmenopausal bleeding and sonographic endometrial thickness ≥ 4.5 mm but without fluid in the uterine cavity. The following features were rated: endometrial echogenicity, endometrial midline, bright edge, endometrial-myometrial junction, color score, vascular pattern, irregularly branching vessels and color splashes. The color content of the endometrial scan was estimated using a visual analog scale graded from 0 to 100. To estimate intrarater agreement and reliability, the same videoclips were assessed twice with a minimum of 2 months' interval. The raters were blinded to their own results and to those of the other raters. Interrater differences in the described prevalence of most IETA variables were substantial, and some variable categories were observed rarely. Specific agreement was poor for variables with many categories. For binary variables, specific agreement was better for absence than for presence of a category. For variables with more than two outcome categories, specific agreement for expert and non-expert raters was best for not-defined endometrial midline (93% and 96%), regular endometrial-myometrial junction (72% and 70%) and three-layer endometrial pattern (67% and 56%). The grayscale ultrasound variable with the best reliability was uniform vs non-uniform echogenicity (multirater kappa (κ), 0.55 for expert and 0.52 for non-expert raters), and the variables with the lowest reliability were appearance of the endometrial-myometrial junction (κ, 0.25 and 0.16) and the nine-category endometrial echogenicity variable (κ, 0.29 and 0.28). The most reliable color Doppler variable was color score (mean weighted

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

    Science.gov (United States)

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

    2016-09-20

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

  14. Clinicopathologic Aspects of Endometrial Proliferous Processes in Women of Reproductive Age

    Directory of Open Access Journals (Sweden)

    Iryna Vovk

    2018-01-01

    Full Text Available The peculiarities of benign proliferative pathology of endometrium including their combination in women of reproductive age are reviewed in the article. Materials and methods. The results of pathohistological research of benign proliferative pathology of endometrium (without atypia were analyzed. Statistical data processing was performed by means of MedStat software package. Results. The obtained results revealed that benign proliferative pathology of endometrium is one of the most frequent gynaecological malignancies among female patients of reproductive age accounting for 52.2 % cases. Endometrial polyps were found to be accompanied by morphological peculiarities indicating chronic inflammatory process in endometrium in 56.5% cases (р<0.05 in comparison with endometrial hyperplasia in 38.2% cases, proving the presence of long-term inflammation in endometrial tissue and its trigger role in the development of the proliferative processes. Among patients with chronic salpingo-oophoritis, infertility was revealed in almost half of cases (44.5% of patients with endometrial polyps, 40.5% of patients with endometrial hyperplasia and 48.3% of women with combined proliferative pathology of endometrium clinically confirming the data of morphological research. Peculiar signs of proliferative processes in genitals were determined, namely coexistence of uterine and endometrial pathology: endometrial hyperplasia was found in 40.4% of patients with uterine leiomyoma and 30.3% of patients with adenomyosis. The same combinations were peculiar for patients with endometrial polyps: endometrial hyperplasia was found in 30.1% of patients with uterine leiomyoma and 36.3% of patients with adenomyosis. Menstrual disorders were revealed in every third woman with endometrial hyperplasia (30.3% and co-existent polyposis (30.2%.

  15. A comparative study of Cyclofem and depot medroxyprogesterone acetate (DMPA) effects on endometrial vasculature.

    Science.gov (United States)

    Simbar, Masoumeh; Tehrani, Fahimeh Ramezani; Hashemi, Zeinab; Zham, Hananeh; Fraser, Ian S

    2007-10-01

    The most common reason for discontinuation of long-acting progestogen-only contraceptives is irregular bleeding following local endometrial vascular changes. To reduce unpredictable bleeding episodes among depot medroxyprogesterone acetate (DMPA) users, the combined injectable contraceptive, Cyclofem, was offered as an alternative. However, there is a gap in our knowledge about the effects of Cyclofem on the endometrial vasculature and patterns of bleeding. This study aimed to compare the effects of Cyclofem and DMPA on endometrial vascular density, endometrial histology and pattern of bleeding. Sixty-eight healthy women with regular menstrual bleeding and seeking injectable long-acting contraceptives were recruited. Two endometrial samples (before and 3 to 6 months after initial exposure to DMPA or Cyclofem) were collected from each participant. The samples were stained using an immunohistochemical method and anti-CD34 to visualise the endometrial vasculature. Endometrial vascular density was assessed using standard techniques. Sixty-eight women were randomly assigned to Cyclofem (38 women) or DMPA (30 women). Endometrial vascular density was 149.3 +/- 6.7 (mean +/- SD)/mm(2) before injection. This significantly decreased to 132.4 +/- 12.2 after DMPA use, and from 151.9 +/- 5.8 to 131.8 +/- 12.8 vessels/mm(2) following Cyclofem use (paired t-test, p Spotting was the most common type of bleeding experienced, and atrophic endometrium was the most common histological pattern observed in both groups. This study demonstrated that both Cyclofem and DMPA use are associated with decreased endometrial vascular density and atrophic endometrium, in addition to irregular bleeding, mainly spotting. There was no significant difference in bleeding patterns or endometrial findings observed for these two injectable contraceptives in Iranian women.

  16. Altered protein expression in serum from endometrial hyperplasia and carcinoma patients

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    Cong Qing

    2011-04-01

    Full Text Available Abstract Background Endometrial carcinoma is one of the most common gynecological malignancies in women. The diagnosis of the disease at early or premalignant stages is crucial for the patient's prognosis. To date, diagnosis and follow-up of endometrial carcinoma and hyperplasia require invasive procedures. Therefore, there is considerable demand for the identification of biomarkers to allow non-invasive detection of these conditions. Methods In this study, we performed a quantitative proteomics analysis on serum samples from simple endometrial hyperplasia, complex endometrial hyperplasia, atypical endometrial hyperplasia, and endometrial carcinoma patients, as well as healthy women. Serum samples were first depleted of high-abundance proteins, labeled with isobaric tags (iTRAQ™, and then analyzed via two-dimensional liquid chromatography and tandem mass spectrometry. Protein identification and quantitation information were acquired by comparing the mass spectrometry data against the International Protein Index Database using ProteinPilot software. Bioinformatics annotation of identified proteins was performed by searching against the PANTHER database. Results In total, 74 proteins were identified and quantified in serum samples from endometrial lesion patients and healthy women. Using a 1.6-fold change as the benchmark, 12 proteins showed significantly altered expression levels in at least one disease group compared with healthy women. Among them, 7 proteins were found, for the first time, to be differentially expressed in atypical endometrial hyperplasia. These proteins are orosomucoid 1, haptoglobin, SERPINC 1, alpha-1-antichymotrypsin, apolipoprotein A-IV, inter-alpha-trypsin inhibitor heavy chain H4, and histidine-rich glycoprotein. Conclusions The differentially expressed proteins we discovered in this study may serve as biomarkers in the diagnosis and follow-up of endometrial hyperplasia and endometrial carcinoma.

  17. HE4 Transcription- and Splice Variants-Specific Expression in Endometrial Cancer and Correlation with Patient Survival

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    Shi-Wen Jiang

    2013-11-01

    Full Text Available We investigated the HE4 variant-specific expression patterns in various normal tissues as well as in normal and malignant endometrial tissues. The relationships between mRNA variants and age, body weight, or survival are analyzed. ICAT-labeled normal and endometrial cancer (EC tissues were analyzed with multidimensional liquid chromatography followed by tandem mass spectrometry. Levels of HE4 mRNA variants were measured by real-time PCR. Mean mRNA levels were compared among 16 normal endometrial samples, 14 grade 1 and 14 grade 3 endometrioid EC, 15 papillary serous EC, and 14 normal human tissue samples. The relationship between levels of HE4 variants and EC patient characteristics was analyzed with the use of Pearson correlation test. We found that, although all five HE4 mRNA variants are detectable in normal tissue samples, their expression is highly tissue-specific, with epididymis, trachea, breast and endometrium containing the highest levels. HE4-V0, -V1, and -V3 are the most abundant variants in both normal and malignant tissues. All variants are significantly increased in both endometrioid and papillary serous EC, with higher levels observed in grade 3 endometrioid EC. In the EC group, HE4-V1, -V3, and -V4 levels inversely correlate with EC patient survival, whereas HE4-V0 levels positively correlate with age. HE4 variants exhibit tissue-specific expression, suggesting that each variant may exert distinct functions in normal and malignant cells. HE4 levels appear to correlate with EC patient survival in a variant-specific manner. When using HE4 as a biomarker for EC management, the effects of age should be considered.

  18. Adipose tissue concentrations of PCB, HCB, chlordane, PBDE and P,P'-DDE and the risk for endometrial cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lindstroem, G.; Bavel, B. van; Bjoernfoth, H. [MTM Research Centre, Oerebro Univ., Oerebro (Sweden); Hardell, L. [Dept. of Oncology, Univ. Hospital, Oerebro (Sweden)

    2004-09-15

    Environmental pollutants with hormonal activity, such as xenoestrogens, have for several years been of concern as potential risk factors for hormone dependant tumors. Impacts of increasing levels of xenoestrogens have been observed in aquatic organisms. In humans concern has been focused on ''endocrine disrupting chemicals'' with either estrogenic or antiestrogenic activities. Some persistent organic pollutants (POPs) such as polychlorinated biphenyls (PCBs), and especially the hydroxylated metabolites, and chlordanes, have been postulated to be endocrine disruptors. PCBs have been shown to reverse gonadal sex in turtle5 and abnormalities of reproductive development has been described in juvenile alligators living in contaminated environment in Florida. Hexachlorobenzene (HCB) has been shown to have endocrine-disrupting properties. Also p,p'-dichlorodiphenyl-dichloroethylene (p,p'-DDE) the most persistent metabolite of p,p'-DDT has been postulated to be an environmental endocrine disruptor. In a case-control study on patients with testicular cancer we found higher concentrations of PCBs, HCB and chlordanes in mothers to cases than in mothers to controls. Similar concentrations were found in cases with testicular cancer as in the population controls. The study gave support to the hypothesis that exposure to endocrine disruptors during the fetal period may be of etiologic importance in the etiology of testicular cancer. Another hormone dependent cancer is endometrial cancer. It accounted for 5.8% of all cancers incidents among Swedish women in 2002. The cumulative probability of developing the disease before 85 years of age was 2.8% in 2002. Estrogen replacement has been suggested as a risk factor among several others. The first cases of endometrial cancer among women using estrogen replacement therapy were reported in early 1960's. Is there a relationship between levels of POPs and incidence rate? The aim is to investigate

  19. Methylation Analysis of DNA Mismatch Repair Genes Using DNA Derived from the Peripheral Blood of Patients with Endometrial Cancer: Epimutation in Endometrial Carcinogenesis

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    Takashi Takeda

    2016-10-01

    Full Text Available 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.

  20. Endometrial natural killer (NK) cells reveal a tissue-specific receptor repertoire.

    Science.gov (United States)

    Feyaerts, D; Kuret, T; van Cranenbroek, B; van der Zeeuw-Hingrez, S; van der Heijden, O W H; van der Meer, A; Joosten, I; van der Molen, R G

    2018-02-13

    subpopulation expansions in eNK and pbNK cells, respectively. In contrast to the pbNK cell population, the expansions present in the eNK cell population were independent of CMV status and HLA-C genotype. Moreover, the typical NKG2C imprint induced by CMV infection on pbNK cells was not observed on eNK cells from the same female, suggesting a rapid local turnover of eNK cells and/or a distinct licensing process. Based on our previous work and the parameters studied here, menstrual blood-derived eNK cells closely resemble biopsy-derived eNK cells. However, sampling is not done at the exact same time during the menstrual cycle, and therefore we cannot exclude some, as yet undetected, differences. Our data reveals that NK cells in the pre-implantation endometrium appear to have a dedicated tissue-specific phenotype, different from NK cells in peripheral blood. This may indicate that eNK cells are finely tuned to receive an allogeneic fetus. Studying the endometrial NKR repertoire of women with pregnancy related problems could provide clues to understand the pathogenesis of pregnancy complications. No external funding was obtained for the present study. None of the authors has any conflict of interest to declare. NA. © The Author(s) 2018. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

  1. Adjuvant treatment and outcomes of stage III endometrial carcinoma

    International Nuclear Information System (INIS)

    Connell, C.; Ludbrook, J.; Davy, M.; Yeoh, E

    2003-01-01

    Surgery with staging using FIGO (1988) classification is accepted management for stage III endometrial carcinoma. The delivery of adjuvant therapy is controversial and tends to be individualised. Retrospective review of stage III endometrial carcinoma patients who underwent radical surgery at the Royal Adelaide and Queen Elizabeth Hospitals from 1984 to 2003 was carried out. Medical records were reviewed for details of patient characteristics, surgery, histopathology, adjuvant therapy and recurrence/survival. Sixty-six patients with a median age of 69 (37-97), had a median follow-up of 26 months (1-188 ). For all stage III patients, the actuarial 5-year disease-free and overall survivals were 50 and 43% respectively. Thirty-five patients received pelvic +/- paraaortic radiotherapy, 5 whole abdominal radiotherapy, 14 vaginal brachytherapy boost, 10 chemotherapy and 13 adjuvant hormones. Forty-six percent of patients recurred in a median time of 13 months (0-95). For these patients, the sites of first recurrence were pelvis in 27%, pelvis and abdomen in 23%, abdomen alone in 13%, distant alone in 27%, distant and abdominal in 7% and all three sites in 3%. On univariate analysis disease-free survival was impacted by; age, grade, parametrial involvement, number of extrauterine sites, lymphovascular invasion, adjuvant radiotherapy to the pelvis alone and postoperative macroscopic residual disease. Lymphovascular invasion, post-operative residual disease and adjuvant pelvic radiotherapy remained significant on multivariate analysis. These outcomes for stage III endometrial carcinoma are comparable to the current literature. Ongoing research is required to establish the most appropriate adjuvant therapy in these high risk patients

  2. Second-generation endometrial ablation technologies: the hot liquid balloons.

    Science.gov (United States)

    Vilos, George A; Edris, Fawaz

    2007-12-01

    Hysteroscopic endometrial ablation (HEA) was introduced in the 1980s to treat menorrhagia. Its use required additional training, surgical expertise and specialized equipment to minimize emergent complications such as uterine perforations, thermal injuries and excessive fluid absorption. To overcome these difficulties and concerns, thermal balloon endometrial ablation (TBEA) was introduced in the 1990s. Four hot liquid balloons have been introduced into clinical practice. All systems consist of a catheter (4-10mm diameter), a silicone balloon and a control unit. Liquids used to inflate the balloons include internally heated dextrose in water (ThermaChoice, 87 degrees C), and externally heated glycine (Cavaterm, 78 degrees C), saline (Menotreat, 85 degrees ) and glycerine (Thermablate, 173 degrees C). All balloons require pressurization from 160 to 240 mmHg for treatment cycles of 2 to 10 minutes. Prior to TBEA, preoperative endometrial thinning, including suction curettage, is optional. Several RCTs and cohort studies indicate that the advantages of TBEA include portability, ease of use and short learning curve. In addition, small diameter catheters requiring minimal cervical dilatation (5-7 mm) and short duration of treatment cycles (2-8 min) allow treatment under minimal analgesia/anesthesia requirements in a clinic setting. Following TBEA serious adverse events, including thermal injuries to viscera have been experienced. To minimize such injuries some surgeons advocate the use of routine post-dilatation hysteroscopy and/or ultrasonography to confirm correct intrauterine placement of the balloon prior to initiating the treatment cycle. After 10 years of clinical practice, TBEA is thought to be the preferred first-line surgical treatment of menorrhagia in appropriately selected candidates. Economic modeling also suggested that TBEA may be more cost-effective than HEA.

  3. Endometrial preparation with desogestrel before Essure hysteroscopic sterilization: preliminary study.

    Science.gov (United States)

    Haimovich, Sergio; Mancebo, Gemma; Alameda, Francesc; Agramunt, Silvia; Hernández, José Luis; Carreras, Ramón

    2013-01-01

    To assess the effect of desogestrel on endometrial preparation for transcervical sterilization using the Essure device. Prospective nonrandomized clinical study (Canadian Task Force classification II-3). Acute-care university-affiliated hospital in Barcelona, Spain. Women undergoing sterilization using the Essure device between January 2010 and January 2011. Participants were offered desogestrel, 75 μg/d, for 6 weeks before the procedure. Sixteen who accepted were included in the desogestrel group, and 18 who refused were allocated to the no-treatment group. Endometrial biopsy samples were also obtained. In women who received desogestrel, decidual transformation was observed in eight, glandular atrophy in three, and proliferative endometrium in five. In the no-treatment group, two women had menstruation, nine had proliferative endometrium, and seven had secretory endometrium. In the desogestrel group, the procedure was successful in all women. In the no-treatment group, the procedure was cancelled in two women because of menstruation and in four women with secretory endometrium in whom the tubal ostia were difficult to visualize because of endometrial thickness and bleeding. The median (interquartile range, 25th-75th percentile) duration of the procedure was shorter in the desogestrel group than in the no-treatment group (7 [6-7] minutes vs 8 [7-12] minutes; p = .002). Desogestrel, 75 μg/d, could be an alternative to combined hormonal contraception before placement of Essure inserts, facilitating the procedure and serving as a contraceptive method during the following 12 weeks until occlusion of the tubes. Copyright © 2013 AAGL. Published by Elsevier Inc. All rights reserved.

  4. Evaluating the potential bioactivity of a novel compound ER1626.

    Science.gov (United States)

    Wang, Lijun; Zeng, Yanyan; Wang, Tianling; Liu, Hongyi; Xiao, Hong; Xiang, Hua

    2014-01-01

    ER1626, a novel compound, is a derivate of indeno-isoquinoline ketone. This study was designed to evaluate the biological activity and potential anti-tumor mechanism of ER1626. MTT assay, scratch assay and flow cytometry were used to determine cell proliferation, cell migration and cell cycle distribution as well as cell apoptosis on human breast cancer MCF-7 cells and endometrial cancer Ishikawa cells. We also explored the antiangiogenic effect of ER1626 on HUVEC cells and chicken embryos. The expression of estrogen receptor protein was investigated with western-blot analysis. ER1626 down-regulated the expression of estrogen receptor α protein and up-regulated β protein in MCF-7 and Ishikawa cells. The value of IC50 of ER1626 on MCF-7 and Ishikawa cells were respectively 8.52 and 3.08 µmol/L. Meanwhile, ER1626 decreased VEGF secretion of MCF-7 and Ishikawa cells, disturbed the formation of VEGF-stimulated tubular structure in HUVEC cells, and inhibited the angiogenesis on the chicken chorioallantoic membrane. Scratch assay revealed that ER1626 suppressed the migration of MCF-7, Ishikawa and HUVEC cells. In addition to induction tumor cell apoptosis, ER1626 arrested cell cycle in G1/G0 phase in MCF-7 cells and G2/M phase in Ishikawa cells. In conclusion, our results demonstrated that ER1626 has favorable bioactivities to be a potential candidate against breast cancer and angiogenesis.

  5. Evaluating the potential bioactivity of a novel compound ER1626.

    Directory of Open Access Journals (Sweden)

    Lijun Wang

    Full Text Available ER1626, a novel compound, is a derivate of indeno-isoquinoline ketone. This study was designed to evaluate the biological activity and potential anti-tumor mechanism of ER1626.MTT assay, scratch assay and flow cytometry were used to determine cell proliferation, cell migration and cell cycle distribution as well as cell apoptosis on human breast cancer MCF-7 cells and endometrial cancer Ishikawa cells. We also explored the antiangiogenic effect of ER1626 on HUVEC cells and chicken embryos. The expression of estrogen receptor protein was investigated with western-blot analysis.ER1626 down-regulated the expression of estrogen receptor α protein and up-regulated β protein in MCF-7 and Ishikawa cells. The value of IC50 of ER1626 on MCF-7 and Ishikawa cells were respectively 8.52 and 3.08 µmol/L. Meanwhile, ER1626 decreased VEGF secretion of MCF-7 and Ishikawa cells, disturbed the formation of VEGF-stimulated tubular structure in HUVEC cells, and inhibited the angiogenesis on the chicken chorioallantoic membrane. Scratch assay revealed that ER1626 suppressed the migration of MCF-7, Ishikawa and HUVEC cells. In addition to induction tumor cell apoptosis, ER1626 arrested cell cycle in G1/G0 phase in MCF-7 cells and G2/M phase in Ishikawa cells.In conclusion, our results demonstrated that ER1626 has favorable bioactivities to be a potential candidate against breast cancer and angiogenesis.

  6. Pseudolipomatosis in Endometrial Specimens Does Not Represent Uterine Perforation.

    Science.gov (United States)

    Heller, Alexis

    2017-02-01

    Specimens of endometrial biopsies can sometimes present with an artifact within blood, composed of optically clear vacuoles mimicking adipose tissue, pseudolipomatosis. This artifact can be mistaken for adipose tissue and lead to an overdiagnosis of uterine perforation. We describe the case of pseudolipomatosis seen within the evacuated products of conception from a missed abortion. Areas of vacuolization in the blood clot mimicked adipose tissue. However, the vacuoles varied in size and did not contain adipocytes. Familiarity with this artifact will lead to avoidance of overdiagnosis of adipose tissue and uterine perforation in curettage specimens.

  7. Determination of extent of surgical intervention for endometrial carcinoma

    International Nuclear Information System (INIS)

    Smakhtina, O.L.; Nugmanova, M.I.; Nigaj, S.V.

    1986-01-01

    Clinical, cytologic, histologic and X-ray procedures were used in examining 120 patients with endometrial carcinoma. The results of pre- and intraoperative determination of clinical stage were compared in 65 cases of uterine extirpation with appendages and lymphadenectomy. Errors in preoperative identification of the extent of tumor expansion were made in 9 cases (13.8+-4.3%). It was found that determinations of the site and expansion of tumor make the case for hysterocervico-angiolymphography whereas identification of tumor pattern and degree of cell differentiation-for cytologic and histologic assays

  8. Study of hormonal status of surgical patients with endometrial carcinoma

    International Nuclear Information System (INIS)

    Musina, R.Kh.; Kiseleva, N.S.; Modnikov, O.P.

    1987-01-01

    A radioimmunoassay was conducted in the pituitary-ovary and pituitary-adrenals systems in 37 cases of endometrial carcinoma treatment and 1, 3, 5 and 14 days after extirpation of the uterus and appendages. The levels of follicle - stimulating (FSH) and luteinizing (LH) hormones of the pituitary, prolactin, ACTH, estradiol, progesterone, testosterone, cortisol and aldosterone were studied. Such disturbances as decreased production of FSH, LH, progesterone and testosterone were observed before operation. Surgery was followed by a considerable rise in prolactin production and basal levels of FSH and LH, a decrease in estradiol, progesterone and testosterone concentrations and was accompanied by a sizeable release of cortisol and aldosterone

  9. Clinical and cytological definition of endometrial cancer during radiotherapy

    International Nuclear Information System (INIS)

    Titova, V.A.; Titova, N.P.

    1981-01-01

    The state of primary tumor in 45 patients with adenocarcinoma of the endometrium, stage 1-3, during concomitant radical radio-and hormonotherapy according to the data of hysterocervicography, hysterometry and cytohistology have been studied. Contact irradiation was performed in single fractions of 9.5-10.0 Gy per week. The time course of primary uterine tumor regression was observed with regard to various radiation dose levels in accordance with cytological data. The cytological method is regarded as an important quantitative criterion in the evaluation of radio- and hormonotherapeutic efficacy of inoperable endometrial cancer [ru

  10. Roles of the insulinlike growth factor family in nonpregnant human endometrium and at the decidual: trophoblast interface.

    Science.gov (United States)

    Giudice, L C; Irwin, J C

    1999-01-01

    The insulinlike growth factor (IGF) family is believed to be important in endometrial development during the menstrual cycle and in the process of implantation. The mitogenic, differentiative, and antiapoptotic properties of the IGFs and their binding proteins, as well as their spatial and temporal expression in cycling endometrium, suggest that they may participate in endometrial growth, differentiation, apoptosis, and perhaps angiogenesis. IGFBP proteases, which increase IGF bioavailability, have been localized to endometrial stromal cells and to the human cytotrophoblast and likely play important roles in endometrial, decidual, and trophoblast physiology. IGFBP-1 is a major protein product of nonpregnant endometrium during the mid-late secretory phase and occurs in abundance in decidua. Its roles as an IGF-binding protein and as a trophoblast integrin ligand suggest that it may have multiple roles in endometrial development and in interactions between the decidua and the invading trophoblast. Recent evidence suggests that it may have a role in the process of shallow implantation in the clinical disorder of preclampsia. In contrast to knowledge about the roles of IGF peptides, IGFBP proteases, and IGFBPs in normal endometrial development and early human pregnancy, little information is available regarding this family in abnormal endometrial development, in occult endometrial defects, and in uterine receptivity and nonreceptivity.

  11. Atypical endometrial cells and atypical glandular cells favor endometrial origin in Papanicolaou cervicovaginal tests: Correlation with histologic follow-up and abnormal clinical presentations

    Directory of Open Access Journals (Sweden)

    Longwen Chen

    2014-01-01

    Full Text Available The 2001 Bethesda system recommends further classifying atypical glandular cells (AGCs as either endocervical or endometrial origin. Numerous studies have investigated the clinical significance of AGC. In this study, we investigated the incidence of clinically significant lesions among women with liquid-based Papanicolaou cervicovaginal (Pap interpretations of atypical endometrial cells (AEMs or AGC favor endometrial origin (AGC-EM. More importantly, we correlated patients of AEM or AGC-EM with their clinical presentations to determine if AEM/AGC-EM combined with abnormal vaginal bleeding is associated with a higher incidence of significant endometrial pathology. All liquid-based Pap tests with an interpretation of AEM and AGC-EM from July, 2004 through June, 2009 were retrieved from the database. Women with an interpretation of atypical endocervical cells, AGC, favor endocervical origin or AGC, favor neoplastic were not included in the study. The most severe subsequent histologic diagnoses were recorded for each patient. During this 5-year period, we accessioned 332,470 Pap tests of which 169 (0.05% were interpreted as either AEM or AGC-EM. Of the 169 patients, 133 had histologic follow-up within the health care system. The patients ranged in age from 21 to 71 years old (mean 49.7. On follow-up histology, 27 (20.3% had neoplastic/preneoplastic uterine lesions. Among them, 20 patients were diagnosed with adenocarcinoma (18 endometrial, 1 endocervical, and 1 metastatic colorectal, 3 with atypical endometrial hyperplasia, and 4 with endometrial hyperplasia without atypia. All patients with significant endometrial pathology, except one, were over 40 years old, and 22 of 25 patients reported abnormal vaginal bleeding at the time of endometrial biopsy or curettage. This study represents a large series of women with liquid-based Pap test interpretations of AEM and AGC-EM with clinical follow-up. Significant preneoplastic or neoplastic endometrial

  12. Prospective endometrial assessment of breast cancer patients treated with third generation aromatase inhibitors.

    Science.gov (United States)

    Garuti, Giancarlo; Cellani, Fulvia; Centinaio, Giovanna; Montanari, Giuseppe; Nalli, Giulio; Luerti, Massimo

    2006-11-01

    A prospective evaluation of the effects on endometrium of third generation aromatase inhibitors (AIs), administered as adjuvant up-front therapy or switched therapy in menopausal patients suffering from breast cancer. Forty-five patients suffering from estrogen-receptor positive breast cancer were treated with AIs as adjuvant endocrine therapy; 27 patients switched from tamoxifen to AIs (group 1) due to adverse medical events related to tamoxifen intake (22 patients) or to an extended endocrine treatment after 60 months of tamoxifen therapy (5 patients); whereas 18 patients received AIs as up-front adjuvant therapy (group 2). All patients underwent endometrial investigation before the start of AIs therapy and, thereafter, at 12 month intervals. Endometrial assessment was based on Transvaginal Ultrasonography (TU), followed by hysteroscopy and endometrial biopsy when a double layered endometrial stripe above 4 mm was measured on the longitudinal plane of uterine scanning. Six patients, showing endometrial hyperplasia before the start of AIs therapy, underwent hysteroscopy on a yearly basis, disregarding the endometrial thickness measured by TU. Histopathologic results on endometrial biopsies represented the reference test in order to estimate the prevalence of endometrial morbidity. Demographic and clinical variables evaluated (age, parity, age at menarche and menopause, Body Mass Index, previous chemotherapy and radiotherapy) did not differ in groups 1 and 2. The average period of endometrial surveillance after the start of AIs therapy was 24.8 +/-10.8 months for group 1 and 21.4 +/- 11.5 months for group 2. A progressive decrease of endometrial thickness, from 8.2 +/- 5.0 to 3.0 +/- 1.2 in group 1 and from 4.7 +/- 4.3 to 1.9 +/- 0.3 in group 2, was found before the start and after 36-48 months of AIs therapy. The second line endometrial investigations' rate dropped from 70.3% to 12.5% in group 1 and from 27.7% to 0.0% in group 2, at baseline and after 36-48 months

  13. Paeonia lactiflora Enhances the Adhesion of Trophoblast to the Endometrium via Induction of Leukemia Inhibitory Factor Expression.

    Directory of Open Access Journals (Sweden)

    Hee-Jung Choi

    Full Text Available In the present study, we investigated the role of Paeonia lactiflora Pall. extract on embryo implantation in vitro and in vivo. A polysaccharides depleted-water extract of P. lactiflora (PL-PP increased LIF expression in human endometrial Ishikawa cells at non-cytotoxic doses. PL-PP significantly increased the adhesion of the human trophectoderm-derived JAr spheroids to endometrial Ishikawa cells. PL-PP-induced LIF expression was decreased in the presence of a p38 kinase inhibitor SB203580 and an MEK/ERK inhibitor U0126. Furthermore, endometrial LIF knockdown by shRNA reduced the expression of integrins β3 and β5 and adhesion of JAr spheroids to Ishikawa cells. In vivo administration of PL-PP restored the implantation of mouse blastocysts in a mifepristone-induced implantation failure mice model. Our results demonstrate that PL-PP increases LIF expression via the p38 and MEK/ERK pathways and favors trophoblast adhesion to endometrial cells.

  14. Using gene expression in patients with endometrial intraepithelial neoplasia to assess the risk of cancer

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    Koah Vierkoetter

    2018-05-01

    Full Text Available Patients diagnosed with an endometrial cancer precursor lesion on biopsy may be found to have endometrial cancer at the time of subsequent surgery. The current study seeks to identify patients with endometrial intraepithelial neoplasia (EIN on biopsy that may be harboring an occult carcinoma. Immunohistochemical stains for gene loss of expression (LOE for 6 genes, PTEN, ARID1A, MSH6, MSH2, MLH1, and PMS2, were performed on 113 biopsy specimens with EIN. For the 95 patients with follow-up histology, 40 patients had cancer, 41 had EIN, and 14 had normal endometrium. PTEN LOE was found frequently in both EIN and endometrial cancer, and therefore had low positive predictive value. All specimens with ARID1A, MSH6, MSH2, MLH1, or PMS2 LOE on biopsy were subsequently found to have cancer. LOE of any gene was associated with modest sensitivity (0.78 in identifying patients with endometrial cancer who had EIN on biopsy. Further investigation is warranted to determine if gene LOE is a useful clinical tool when evaluating patients with EIN on biopsy. Keywords: Endometrial intraepithelial neoplasia, Endometrial cancer, Gene expression, PTEN, ARID1A, Mismatch repair genes

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

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    Jehn-Hsiahn Yang

    Full Text Available 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.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.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.A higher number of endometrial polyps and longer follow-up duration are associated with a greater potential of polyp recurrence after hysteroscopic polypectomy.

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

    Directory of Open Access Journals (Sweden)

    Beata Leśniczak

    2015-09-01

    Full Text Available 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.

  17. Glycogen Synthase Kinase 3β Inhibition as a Therapeutic Approach in the Treatment of Endometrial Cancer

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    Liang Ma

    2013-08-01

    Full Text Available Alternative strategies beyond current chemotherapy and radiation therapy regimens are needed in the treatment of advanced stage and recurrent endometrial cancers. There is considerable promise for biologic agents targeting the extracellular signal-regulated kinase (ERK pathway for treatment of these cancers. Many downstream substrates of the ERK signaling pathway, such as glycogen synthase kinase 3β (GSK3β, and their roles in endometrial carcinogenesis have not yet been investigated. In this study, we tested the importance of GSK3β inhibition in endometrial cancer cell lines and in vivo models. Inhibition of GSK3β by either lithium chloride (LiCl or specific GSK3β inhibitor VIII showed cytostatic and cytotoxic effects on multiple endometrial cancer cell lines, with little effect on the immortalized normal endometrial cell line. Flow cytometry and immunofluorescence revealed a G2/M cell cycle arrest in both type I (AN3CA, KLE, and RL952 and type II (ARK1 endometrial cancer cell lines. In addition, LiCl pre-treatment sensitized AN3CA cells to the chemotherapy agent paclitaxel. Administration of LiCl to AN3CA tumor-bearing mice resulted in partial or complete regression of some tumors. Thus, GSK3β activity is associated with endometrial cancer tumorigenesis and its pharmacologic inhibition reduces cell proliferation and tumor growth.

  18. Median Survival Time of Endometrial Cancer Patients with Lymphovascular Invasion at the Hospital Universiti Sains Malaysia.

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    Asyikeen, Wan Adnan Wan Nor; Siti-Azrin, Ab Hamid; Jalil, Nur Asyilla Che; Zin, Anani Aila Mat; Othman, Nor Hayati

    2016-11-01

    Endometrial cancer is the most common gynaecologic malignancy among females worldwide. The purpose of this study was to determine the median survival time of endometrial cancer patients at the Hospital Universiti Sains Malaysia (USM). A list of 121 endometrial cancer cases registered at Hospital USM between 2000 until 2011 was retrospectively reviewed. The survival time of the endometrial cancer patients was estimated by Kaplan-Meier survival analysis. Log-rank tests were performed to compare the survival of the patients based on socio-demographics and clinical presentation. Only 108 patients, 87.0%, were included who were of Malay ethnicity. Previous history included menopause in 67.6% of patients and diabetes mellitus in 39.8% of patients; additionally, 63.4% of patients were nulliparous. Tumour staging was as follows: 24.5% stage I, 10.8% stage II, 26.5% stage III and 38.2% stage IV. The overall median survival time of the endometrial cancer patients was 70.20 months (95% confidence interval (CI): 51.79, 88.61). The significant factors were age, the presence of lymphovascular invasion and treatment received. The overall survival of endometrial cancer was low. A prospective study needs to be carried out to discover more effective and accurate tests for the early detection of endometrial cancer.

  19. Endometrial carcinoma with yolk sac tumor-like differentiation and elevated serum ß-hCG: a case report and literature review

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    Ji M

    2013-10-01

    Full Text Available Mingliang Ji,1 Yan Lu,1 Lina Guo,2 Fengzhi Feng,1 Xirun Wan,1 Yang Xiang1 1Department of Obstetrics and Gynecology, 2Department of Pathology, Peking Union Medical College Hospital, Beijing, People's Republic of China Abstract: Endometrial carcinoma with a germ cell tumor component is a rare event. Here we report a uterine neoplasm with a unique combination of endometrioid adenocarcinoma and mixed germ cell malignant elements. A 28-year-old woman with abnormal vaginal bleeding, an abdominal mass, and elevated alfa-fetoprotein and beta-human chorionic gonadotropin (ß-hCG levels had a history of biopsy of an omental mass and chemotherapy in another hospital one month before her referral to our department. Histologic examination of the mass removed from the omentum revealed an endometrioid adenocarcinoma with yolk sac tumor-like differentiation. Total abdominal hysterectomy, bilateral salpingo-oophorectomy, infracolic omentectomy, and removal of metastatic disease were then undertaken at our hospital. Postoperative chemotherapy was given. Eight months postoperatively, serum alfa-fetoprotein and ß-hCG rose again. Cases with primary yolk sac tumors of the endometrium or endometrial carcinoma with trophoblastic differentiation in the literature were reviewed. Keywords: endometrial carcinoma, yolk sac tumor, trophoblastic differentiation

  20. Modified hMG stimulated: an effective option in endometrial preparation for frozen-thawed embryo transfer in patients with normal menstrual cycles.

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    Huang, Pinxiu; Wei, Lihong; Li, Xinlin; Lin, Zhong

    2018-04-20

    To evaluate the clinical efficacy of modified human menopausal gonadotropin (hMG) stimulated, hormone replacement therapy (HRT), natural cycling and letrozole ovulation induction during endometrial preparation for frozen-thawed embryo transfer (FET) in patients with normal menstrual cycles. This retrospective analysis included a total of 5070 cycles of patients with normal menstrual patterns who underwent FET between October 2009 and September 2015. The patients were divided into four groups according to the method of endometrial preparation for FET: 1838 cycles were natural, 1666 underwent HRT, 340 underwent letrozole ovulation induction and 1226 underwent modified hMG stimulated. Reproduction-related clinical outcomes in the four groups were compared. The clinical pregnancy rates and live birth rates of patients in the modified hMG stimulated group were significantly higher than that in the other groups p .05). Modified hMG stimulated resulted in a higher pregnancy rate compared to the other treatment groups. Therefore, modified hMG stimulated may be an effective option in endometrial preparation for FET in patients with normal menstrual cycles.

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

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    Croxatto Horacio B

    2011-01-01

    Full Text Available Abstract 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

  2. The fate of autologous endometrial mesenchymal stromal cells after application in the healthy equine uterus.

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    Rink, Elisabeth; Beyer, Teresa; French, Hilari; Watson, Elaine; Aurich, Christine; Donadeu, Xavier

    2018-05-23

    Because of their distinct differentiation, immunomodulatory and migratory capacities, endometrial mesenchymal stromal cells (MSCs) may provide an optimum source of therapeutic cells not only in relation to the uterus but also for regeneration of other tissues. This study reports the fate of endometrial MSCs following intrauterine application in mares. Stromal cell fractions were isolated from endometrial biopsies taken from seven reproductively healthy mares, expanded and fluorescence-labeled in culture. MSCs (15 x 106) or PBS were autologously infused into each uterine horn during early diestrus and subsequently tracked by fluorescence microscopy and flow cytometry of endometrial biopsies and blood samples taken periodically after infusion. The inflammatory response to cell infusion was monitored in endometrial cytology samples. MSCs were detected in endometrial sections at 6, 12 and 24 hours but not later (7 or 14 days) after cell infusion. Cells were in all cases located in the uterine lumen, never within endometrial tissue. No fluorescence signal was detected in blood samples at any time point after infusion. Cytology analyses showed an increase in %PMN between 1 and 3 hours after uterine infusion with either MSCs or PBS, and a further increase by 6 hours only in mares infused with PBS. In summary, endometrial MSCs were detected in the uterine lumen for up to 24 h after infusion but did not migrate into healthy endometrium. Moreover, MSCs effectively attenuated the inflammatory response to uterine infusion. We conclude that endometrial MSCs obtained from routine uterine biopsies could provide a safe and effective cell source for treatment of inflammatory conditions of the uterus and potentially other tissues.

  3. Analysis of methylation profiling data of hyperplasia and primary and metastatic endometrial cancers.

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    Wu, Xihai; Miao, Jilan; Jiang, Jingyan; Liu, Fangmei

    2017-10-01

    Endometrial cancer is a prevalent cancer, and its metastasis causes low survival rate. This study aims to utilize DNA methylation data to investigate the mechanism of the development and metastasis of endometrial cancer. Methylation profiling data were down-loaded from Gene Expression Omnibus, including 8 hyperplasias, 33 primary and 53 metastatic endometrial cancers. COHCAP package and annotation files were utilized to identify differentially methylated genes (DMGs) and CpG islands between the three different endometrial diseases. STRING database and Cytoscape were used to analyze and visualize protein-protein interactions (PPIs) between DMGs. CytoNCA plugin was utilized to identify key nodes in PPI network. A total of 610, 1076, and 501 DMGs were identified between primary endometrial cancer and hyperplasia, metastatic endometrial cancer and hyperplasia, as well as metastatic and primary endometrial cancers, respectively. For the three DMG sets, 53 common hypermethylated DMGs (e.g. PAX6 and INSR) and 6 common hypomethylated DMGs (e.g. PRDM8, KLHL14, and DUSP6) were found. For primary-hyperplasia DMG set and metastasis-hyperplasia DMG set, 527 common DMGs were found. For these common DMGs, a PPI network involving 692 PPIs was constructed. For DMGs between metastatic and primary endometrial cancers, a PPI network involving 673 PPIs was established, with PAX6 and INSR in the top 20 DMGs in both networks. PRDM8, KLHL14, and DUSP6 had hypomethylated CpG islands. DMGs comparison, PPI network analysis, and analysis of differentially methylated CpG islands indicated that PAX6, INSR, PRDM8, KLHL14, and DUSP6 might participate in the development and metastasis of endometrial cancer. Copyright © 2017. Published by Elsevier B.V.

  4. Decreased endometrial vascularity and receptivity in unexplained recurrent miscarriage patients during midluteal and early pregnancy phases.

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    Tan, Shu-Yin; Hang, Fu; Purvarshi, Gowreesunkur; Li, Min-Qing; Meng, Da-Hua; Huang, Ling-Ling

    2015-10-01

    To evaluate the predictive value of three-dimensional (3D)-power Doppler sonography on recurrent miscarriage. The study patients were divided into a recurrent miscarriage group (30 cases) and a normal pregnancy group (21 cases). Measurement of endometrial thickness was performed using two-dimensional transvaginal ultrasound in the midluteal phase. The endometrial volume, vascularization index (VI), flow index (FI), and vascularization-flow index (VFI) in midluteal and placenta volume, as well as the VI, FI, and VFI of early pregnancy were measured using Virtual Organ Computer-aided Analysis of 3D-power Doppler ultrasound. Endometrial thickness, endometrial volume, endometrial vascular data, VI, FI, and VFI of the midluteal phase were lower in the recurrent miscarriage group compared with the normal pregnancy group (p FI between the recurrent miscarriage and control groups during early pregnancy (p > 0.05). The predictive accuracy of endometrial thickness, endometrial volume, VI, FI, and VFI in the midluteal phase, and placenta volume, VI, FI, and VFI in early pregnancy as measured by the receiver operating characteristic curve to predict miscarriage before 12 gestational weeks in participants was 0.681, 0.876, 0.770, 0.720, 0.879, 0.771, 0.907, 0.592, respectively. The 3D-power Doppler ultrasound is a more comprehensive and sensitive method for evaluating endometrial receptivity. Endometrial volume, VI, FI, and VFI in the midluteal phase, as well as VI in early pregnancy, can be considered as predictive factors for recurrent miscarriage. Copyright © 2015. Published by Elsevier B.V.

  5. The γ-aminobutyric acid-producing ability under low pH conditions of lactic acid bacteria isolated from traditional fermented foods of Ishikawa Prefecture, Japan, with a strong ability to produce ACE-inhibitory peptides.

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    Barla, Florin; Koyanagi, Takashi; Tokuda, Naoko; Matsui, Hiroshi; Katayama, Takane; Kumagai, Hidehiko; Michihata, Toshihide; Sasaki, Tetsuya; Tsuji, Atsushi; Enomoto, Toshiki

    2016-06-01

    Many traditional fermented products are onsumed in Ishikawa Prefecture, Japan, such as kaburazushi , narezushi , konkazuke , and ishiru. Various kinds of lactic acid bacteria (LAB) are associated with their fermentation, however, characterization of LAB has not yet been elucidated in detail. In this study, we evaluated 53 isolates of LAB from various traditional fermented foods by taxonomic classification at the species level by analyzing the 16S ribosomal RNA gene (rDNA) sequences and carbohydrate assimilation abilities. We screened isolates that exhibited high angiotensin-converting enzyme (ACE) inhibitory activities in skim milk or soy protein media and produced high γ-aminobutyric acid (GABA) concentrations in culture supernatants when grown in de Man Rogosa Sharpe broth in the presence of 1% (w/v) glutamic acid. The results revealed that 10 isolates, i.e., Lactobacillus buchneri (2 isolates), Lactobacillus brevis (6 isolates), and Weissella hellenica (2 isolates) had a high GABA-producing ability of >500 mg/100 ml after 72 h of incubation at 35 °C. The ACE inhibitory activity of the whey cultured with milk protein by using L. brevis (3 isolates), L. buchneri (2 isolates), and W. hellenica (2 isolates) was stronger than that of all whey cultured with soy protein media, and these IC 50 were GABA-producing activities at pH 3, suggesting that they could be powerful candidates for use in the fermentation of food materials having low pH.

  6. The usefulness of transvaginal ultrasonography and MRI in endometrial carcinoma

    International Nuclear Information System (INIS)

    Yoshihara, Eisuke

    1992-01-01

    Between October 1988 and March 1991, 29 patients with endometrial carcinoma had both transvaginal ultrasonography (TVUS) and magnetic resonance imaging (MRI) performed following hysterectomy at the Department of Gynecology and Obstetrics, Okayama University Medical School. The findings were compared with the pathological findings to determine the usefulness of each method. The sensitivity of detecting myometrial invasion was 100% by TVUS and 96% by MRI. The accuracy was 86% by each method. The depth of myometrial invasion was classified into 3 degrees [no myometrial invasion, superficial invasion (≤1/2), deep invasion (>1/2)]. The correct diagnostic rate was 86% by TVUS and MRI. The minimum width and the minimum/maximum width ratio of the intact myometrium obtained by each method in the pathological deep invasion group were significantly lower than those obtained in the other two groups (p<0.01). The sensitivity, the accuracy and the specificity for detecting cervical invasion were 89%, 93% and 95% by both methods. There was no difference between TVUS and MRI for diagnosing myometrial and cervical invasion of endometrial carcinoma. (author)

  7. Avaliação de morfologia e histologia endometrial de mulheres após a menopausa Assessment of endometrial morphology and histology in postmenopausal women

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    Luis Paulo Galvao Wolff

    2010-01-01

    Full Text Available OBJETIVO: Avaliar ambulatorialmente a morfologia e histologia endometrial de mulheres sem sangramento genital após a menopausa. MÉTODOS: Em estudo descritivo foram selecionadas 52 mulheres, após a menopausa, entre 50 e 60 anos, sem terapia hormonal nos últimos seis meses. Todas foram submetidas a exame ultrassonográfico, histeroscópico e biópsias endometriais. RESULTADOS: Das 52 mulheres selecionadas 32 (61,5% apresentaram ultrassonografia normal, cavidade uterina normal com endométrio atrófico à histeroscopia, confirmada pela biópsia endometrial. Vinte (38,4% apresentaram achados histeroscópicos ou histológicos anormais, sendo que apenas cinco destas mostraram endométrio com espessura superior a cinco milímetros ao ultrassom. CONCLUSÃO: A histeroscopia diagnóstica associada à biópsia aspirativa (Pipelle pode evidenciar alterações não observadas ao ultrassom transvaginal.OBJECTIVE: Evaluate in outpatients , the endometrial morphology and histology of non- bleeding postmenopausal women. METHODS: We conducted a descriptive study where 52 menopausal women were selected, between 50 and 60 years of age, who had not used hormone replacement therapy in the last six months and did not present any kind of vaginal bleeding after menopause. These women underwent ultrasound examination, hysteroscopy and biopsy, and then endometrial findings were analyzed. RESULTS: Of the 52 women selected, thirty two (61,5% had normal ultrasound, normal uterine cavity with atrophic endometrium, hysteroscopy, confirmed by endometrial biopsy. Twenty (38,4% had hysteroscopuc and histologic alterations and only five women showed by ultrasound an endometrial thickness of more than five millimeters. CONCLUSION: Diagnostic Hysteroscopy associated with aspiration biopsy (Pipelle performed in the day care facility can reveal endometrial alterations that cannot be diagnosed by transvaginal ultrasound.

  8. Non-steroidal anti-inflammatory drug use and risk of endometrial cancer

    DEFF Research Database (Denmark)

    Verdoodt, Freija; Friis, Søren; Dehlendorff, Christian

    2016-01-01

    OBJECTIVE: Non-steroidal anti-inflammatory drug (NSAID) use has been linked to a reduction in the risk of several cancer types. For endometrial cancer, however, results have been inconsistent. To summarize the available evidence on the risk of endometrial cancer associated with use of aspirin...... a random effects model. RESULTS: Six case-control and seven cohort studies were found eligible for our meta-analysis. We observed risk reductions in endometrial cancer associated with regular use of aspirin (case-control: 11%, cohort: 8%) and NA-NSAIDs (case-control: 9%, cohort: 6%), compared to non...

  9. Effect of immunomodulatory therapy on the endometrial inflammatory response to induced infectious endometritis in susceptible mares

    DEFF Research Database (Denmark)

    Christoffersen, Mette; Woodward, Elizabeth; Bojesen, Anders Miki

    2012-01-01

    endometritis based on their endometrial histopathology and ability to clear an induced uterine inflammation. To investigate the effect of immunomodulatory therapy, the mares were inoculated with 10(5) colony forming units (CFU) Escherichia coli in three consecutive estrus cycles in a modified cross-over study...... inoculation. Endometrial biopsies were recovered 3, 24 and 72 h post inoculation. Relative gene-expression analyses were performed by quantitative reverse transcriptase PCR (qRT-PCR). Endometrial gene expression of inflammatory cytokines was modulated by administration of GC. Expression of proinflammatory...

  10. Diagnostic test of endometrial cytobrush in cases of perimenopausal and postmenopausal hemorrhage

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    Andrijono Andrijono

    2005-06-01

    Full Text Available Perimenopausal menopausal hemorrhage can be due to by a variety of causative factors. One of its dangerous causes is atypical hyperplasia and endometrial carcinoma. There are a number of risk factors for the occurrence of endometrial carcinoma. The group that has this risk belongs to high-risk group. In this high-risk group, it is necessary to have a method to identify the changes in endometrial abnormality. One of the alternatives is the examination of endometrial cytology. The objective of this study was to evaluate the sensitivity, specificity and correlation test between endometrial cytology and endometrial histology. This study was a diagnostic test of cytological examination of the endometrium as compared with endometrial histology. Endometrial cytology was performed with a modification of cytubrush and IUD shell. Specimen was dissolved into the centrifuged NaCl, and its deposits were then processed for cytological examination with Papanicolaou and Giemsa staining. After the taking of cytology, the process was continued with curettage of the endometrium, and the specimens were processed for cytological examination. Both of them were examined by anatomic pathologist. Statistical analysis used diagnostic test using histological examination of curetage specimens as gold standard. During the period of study 45 study samples were collected, among which 12 (26.66% were endometrial adenocarcinoma, 6 (13.33% with atypical hyperplasia, 11 (24.44% with non-atypical hyperplasia, 15 (33.33% were samples without abnormality, and one sample with endometritis. Actual correlation value was 57.8%, correlation because of possibility 3.38%, and correlation not because of possibility 54.42%, potential correlation not because of possibility 96.62%, and Kappa value 0.56. It was concluded that cytological examination of the endometriurn with cytobrush could be employed as a screening method in the abnormalities of endometrial thickness, with

  11. Value of endometrial thickness measurement for diagnosing focal intrauterine pathology in women without abnormal uterine bleeding

    DEFF Research Database (Denmark)

    Dreisler, E; Sorensen, S Stampe; Ibsen, P H

    2009-01-01

    OBJECTIVE: To assess the diagnostic value of transvaginal sonographic (TVS) measurement of endometrial thickness for diagnosing focal intrauterine pathology in women without abnormal uterine bleeding (AUB). METHODS: A random selection from the Danish Civil Registration System was made: 1660 women...... of endometrial thickness is a poor diagnostic test, but is apparently efficacious in excluding focal intrauterine pathology, especially in postmenopausal women. The 4-5-mm threshold conventionally used to exclude endometrial malignancy in women with postmenopausal bleeding is not transferable to women without...

  12. A Selective Biomarker Panel Increases the Reproducibility and the Accuracy in Endometrial Biopsy Diagnosis

    DEFF Research Database (Denmark)

    Nastic, Denis; Shanwell, Emma; Wallin, Keng-Ling

    2017-01-01

    Grading and histologic typing of endometrial cancer in biopsy material has a direct impact on the decision to perform lymphadenectomy and/or omentectomy in many cancer centers. Endometrial biopsies are among the most common general surgical pathology specimens. Multiple studies have shown...... that biopsy diagnosis suffers from a lack of reproducibility. Although many biomarkers have been proposed, none have been demonstrated to improve the diagnosis in the biopsy setting. In this study, 70 biopsies with endometrial carcinoma were supplemented with a biomarker panel consisting of ER, PR, P53...

  13. Assessment of reliability of endometrial brush cytology to determine the etiology of abnormal uterine bleeding and postmenopausal bleeding

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    Erhan Yavuz

    2012-12-01

    Full Text Available Objective: To demonstrate diagnostic efficacy of endometrial cytologic sampling for detection of endometrial pathologies (endometrial hyperplasias and cancers,by comparing endometrial full curettage and endometrial cytologic smear pathologic results performed in patients with abnormal uterine bleeding. Materials and Methods: Totally 109 reproductive and postmenopausal women with abnormal uterine bleeding who applied our clinic between January 2005-June 2010 were included in the study.After measurement of endometrial thickness by transvaginal ultrasound, patients were treated initialy with endometrial cytologic sampling using endometrial brush then endometrial full curettage using sharp curette.Pathology and cytology reports were evaluated retrospectively. Results: The most frequent diagnoses in endometrial cytologic specimens obtained by endometrial brush was nondiagnostic with a rate of 73.7%(n: 42 and 53.8%(n: 28 in postmenopausal women and reproductive period women, respectively.When all patients were analysed together, diagnosis was nondiagnostic in 64.2%(n: 70 (38.5% postmenopausal,25.7% premenopausalof endometrial cytologic samples.Cytologic assessment was resulted as sufficient in only 35.8% (n: 39 of cases.Endometrial full curettage pathologic diagnoses were resulted as insufficient in 56.1%(n: 32of postmenopausal patients and 9.6%(n: 5 of reproductive period cases.The second most frequent diagnosis was endometrial polyp in 13(22.8% patients in postmenopausal period, whereas the most frequent diagnoses in reproductive period were reported as endometrial polyp in 18(34.6% and secretory endometrium in 12(23.1% patients. When full curettage was considered as golden standard method with respect to sample sufficiency;the sensitivity of endometrial cytologic evaluation in postmenopausal patients with regard to sample sufficiency was found as 36%, spesificity 81.3%, positive predictive value 60.0%, negative predictive value 61.9%; the values

  14. Diet-induced obesity impairs endometrial stromal cell decidualization: a potential role for impaired autophagy.

    Science.gov (United States)

    Rhee, Julie S; Saben, Jessica L; Mayer, Allyson L; Schulte, Maureen B; Asghar, Zeenat; Stephens, Claire; Chi, Maggie M-Y; Moley, Kelle H

    2016-06-01

    What effect does diet-induced obesity have on endometrial stromal cell (ESC) decidualization? Diet-induced obesity impairs ESC decidualization. Decidualization is important for successful implantation and subsequent health of the pregnancy. Compared with normal-weight women, obese women have lower pregnancy rates (both spontaneous and by assisted reproductive technology), higher rates of early pregnancy loss and poorer oocyte quality. Beginning at 6 weeks of age, female C57Bl/6J mice were fed either a high-fat/high-sugar diet (HF/HS; 58% Fat Energy/Sucrose) or a diet of standard mouse chow (CON; 13% Fat) for 12 weeks. At this point, metabolic parameters were measured. Some of the mice (n = 9 HF/HS and 9 CON) were mated with reproductively competent males, and implantation sites were assessed. Other mice (n = 11 HF/HS and 10 CON) were mated with vasectomized males, and artificial decidualization was induced. For in vitro human studies of primary ESCs, endometrial tissue was obtained via biopsy from normo-ovulatory patients without history of infertility (obese = BMI > 30 kg/m(2), n = 11 and lean = BMI treatment with cAMP and medroxyprogesterone. The level of expression of decidualization markers was assessed by RT-qPCR (mRNA) and western blotting (protein). ATP content of ESCs was measured, and levels of autophagy were assessed by western blotting of the autophagy regulators acetyl coa carboxylase (ACC) and ULK1 (Ser 317). Autophagic flux was measured by western blot of the marker LC3b-II. Mice exposed to an HF/HS diet became obese and metabolically impaired. HF/HS-exposed mice mated to reproductively competent males had smaller implantation sites in early pregnancy (P obese women than in those of normal-weight women (Ptreatment abrogated this increase. Many aspects of obesity and metabolic impairment could contribute to the decidualization defects observed in the HF/HS-exposed mice. Although our findings suggest that both autophagy and decidualization are impaired

  15. Diagnostic Value of Endometrial Sampling with Pipelle Suction Curettage for Identifying Endometrial Lesions in Patients with Abnormal Uterine Bleeding

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    F Behnamfar

    2004-06-01

    Full Text Available Background: While determining the cause of abnormal uterine bleeding, sampling from the endometrium is necessary. Considering that pipelle suction curettage can be performed on an out patient basis and does not require hospitalization, using anesthesia and cervical dilatation, we performed this study. The aim of this study was to compare the diagnostic value of dilatation and curettage (D&C with pipelle suction curettage. Methods: This study was quasiexperimental on 200 pre and postmenopausal patients with abnormal uterine bleeding who refered to Shabihkhani hospital in Kashan, Iran. Endometrial sampling was performed in all patients with two methods namely pipelle and D&C. A pathologist examined the samples each having a predetermined code. Results: The mean age of subjects was 46.2 ±6.2 years, minimum age was 35 years and the maximum was 70 years. The various pathological lab findings were proliferative endometrium, secretory endometrium, athrophic, decidua, cystic and adenomatous hyperplasia. The reports were the same in two methods except for 2 cases where they were different: secretory endometrium with D&C but cystic hyperplasia in pipelle method. Conclusions: The result of our study shows the comparability of obtaining endometrial sample by pipelle with D&C. Due to comfort and convenience of patients in pipelle methode especially in the office setting which does not need anesthesia, pipelle method can easily be employed instead of D&C. Keywords: Pipelle Suction Curette, Dilatation and Curettage, Premenopause, Postmenopause.

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

    Science.gov (United States)

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

    2013-11-01

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

  17. Total laparoscopic radical hysterectomy with pelvic lymphadenectomy for endometrial cancer.

    Science.gov (United States)

    Vasilescu, C; Stănciulea, Oana; Popa, Monica; Anghel, Rodica; Herlea, V; Florescu, Arleziana

    2008-01-01

    The surgical treatment of endometrial cancer is still a matter of debate. Two of the most controversial issues are the beneficial effect of lymphadenectomy and the feasibility of laparoscopy. The aim of the case report was to describe the feasibility of total laparoscopic radical hysterectomy with pelvic lymphadenectomy in a 56-years-old Caucasian woman diagnosed with endometrial cancer. After a CO2 pneumoperitoneum was created the peritoneum was incised cranially to the para-colic fossa just above the external iliac vessels until the psoas muscle is visualized. The external iliac vessels were identified and lymph nodes from the anterior and the medial surface were removed until the iliac bifurcation and placed in an Endo-bag. The procedure continued with the identification of the hypo-gastric and the umbilical artery which were pulled medially in order to open the obturator fossa and remove the lymphatic tissue superior to the obturator nerve. The next step was the opening of the para-vesical and pararectal spaces by using blunt dissection; this maneuver was facilitated by pulling the uterine fundus towards the opposite direction with the uterine manipulator. The parametrium being isolated between the two spaces can be safely divided. At the superior limit of the parametrium the uterine artery is identified and divided at its origin. Thereafter, by placing the uterine fundus in median and posterior position, the vesicouterine peritoneal fold was opened by scissors and a bladder dissection from the low uterine segment down to the vagina was performed. Then the ureter is dissected, freed from its attachments to the parametria and de-crossed from the uterine artery down to its entry into the bladder. Next the rectovaginal space is opened and the utero-sacral ligaments divided; this allows the division of para-vaginal attachments. The vagina is sectioned and the specimen is extracted transvaginally. Then the vaginal stump was sutured by laparoscopy. Total laparoscopic

  18. A simple method for the prevention of endometrial autolysis in hysterectomy specimens

    OpenAIRE

    Houghton, J P; Roddy, S; Carroll, S; McCluggage, W G

    2004-01-01

    Aims: Uteri are among the most common surgical pathology specimens. Assessment of the endometrium is often difficult because of pronounced tissue autolysis. This study describes a simple method to prevent endometrial autolysis and aid in interpretation of the endometrium.

  19. A recurrent endometrial stromal sarcoma harbors the novel fusion JAZF1-BCORL1

    OpenAIRE

    Allen, Allison J; Ali, Siraj M.; Gowen, Kyle; Elvin, Julia A.; Pejovic, Tanja

    2017-01-01

    Highlights ? Genomic alterations may improve diagnostic certainty and subsequent treatment of endometrial stromal sarcoma. ? Novel JAZF1-BCORL1 mutation was identified. ? Targeted therapeutics to down-stream targets may improve survival benefit in these patients.

  20. Endometrial adenocarcinoma recurrence presenting with tibial metastasis: Report of a case

    Directory of Open Access Journals (Sweden)

    Mehmet Salih Söylemez

    2017-01-01

    Conclusion: Recurrence of endometrial cancer as a solitary bone lesion is a rare situation. Wide resection and reconstruction with an allograft or an intercalar prosthesis might be an option to increase survival and possible cure of the patient.

  1. Self-reported stress and risk of endometrial cancer: a prospective cohort study

    DEFF Research Database (Denmark)

    Nielsen, Naja Rod; Strandberg-Larsen, Katrine; Grønbaek, Morten

    2007-01-01

    OBJECTIVES: To assess a possible relationship between perceived stress and first-time incidence of primary endometrial cancer. Psychological stress may affect the synthesis and metabolism of estrogens and thereby be related to risk of endometrial cancer. METHODS: The 6760 women participating...... in the Copenhagen City Heart Study were asked about their stress level at baseline from 1981 to 1983. These women were prospectively followed up in the Danish nationwide cancer registry until 2000 and ...-up, 72 women were diagnosed with endometrial cancer. For each increase in stress level on a 7-point stress scale, there was a lower risk of primary endometrial cancer (hazard ratio (HR) = 0.88; 95% confidence interval (CI), 0.76-1.01). This inverse association was particularly strong in women who...

  2. Does gestrinone antagonize the effects of estrogen on endometrial implants upon the peritoneum of rats?

    Directory of Open Access Journals (Sweden)

    Vera Lúcia Rodrigues Lobo

    2008-01-01

    Full Text Available OBJECTIVE: To evaluate the effects of estrogen treatment in combination with gestrinone on an experimental rat model of endometriosis. METHODS: Uterine transplants were attached to the peritoneum of female Wistar rats via a surgical autotransplantation technique. The implanted area was measured during the proestrus phase and after hormonal treatment. We performed morphometric analysis and examined the macroscopic and morphometric alterations of endometrial implants after hormonal treatment in ovariectomized rats. RESULTS: The high dose of estrogen caused macroscopic increases in the endometrial implant group compared with other groups, which were similar to increases in the proestrus phase. The low dose showed morphometric development of implants, such as an increase in number of endometrial glands, leukocyte infiltration and mitosis. Gestrinone antagonized both doses of estrogen. CONCLUSION: Our findings suggest that gestrinone antagonizes estrogen's effects on rat peritoneal endometrial implants.

  3. Isolated port-site metastasis after laparoscopic surgery for endometrial cancer: A case report

    OpenAIRE

    Palomba, Stefano; Falbo, Angela; Oppedisano, Rosamaria; Russo, Tiziana; Zullo, Fulvio

    2012-01-01

    ► Isolated port-site metastasis is a rare event after laparoscopy in the surgical staging of endometrial cancer. ► More aggressive strategies in case of potentially increased risk for port-site metastasis are needed.

  4. Lumbee Native American ancestry and the incidence of aggressive histologic subtypes of endometrial cancer

    Directory of Open Access Journals (Sweden)

    Chelsea Zhang

    2015-08-01

    Conclusion: In this retrospective cohort analysis, Lumbee Native American ancestry was not a significant independent predictor of rates of high-risk histological subtypes of endometrial cancer or poor survival outcomes.

  5. Endometrial ablation by rollerball electrocoagulation compared to uterine balloon thermal ablation. Technical and safety aspects.

    NARCIS (Netherlands)

    Zon-Rabelink, I.A.A. van; Vleugels, M.P.; Merkus, J.M.W.M.; Graaf, R.M. de

    2003-01-01

    OBJECTIVE: To compare two methods of endometrial ablation, hysteroscopic rollerball electrocoagulation (RBE) and non-hysteroscopic uterine balloon thermal (UBT) ablation (Thermachoice), regarding intra- and post-operative technical complications and safety aspects. STUDY DESIGN: A randomised

  6. Vaginal vault recurrences of endometrial cancer in non-irradiated patients — Radiotherapy or surgery

    Directory of Open Access Journals (Sweden)

    Hordur Alexander Hardarson

    2015-01-01

    Conclusion: This study indicates that ST is an appropriate treatment for locally recurrent endometrial cancer. Our study involves a limited number of patients and is made retrospectively, therefore prospective and ideally randomized trials evaluating both survival and complications are warranted.

  7. Endometrial Receptivity and its Predictive Value for IVF/ICSI-Outcome.

    Science.gov (United States)

    Heger, A; Sator, M; Pietrowski, D

    2012-08-01

    Endometrial receptivity plays a crucial role in the establishment of a healthy pregnancy in cycles of assisted reproduction. The endometrium as a key factor during reproduction can be assessed in multiple ways, most commonly through transvaginal grey-scale or 3-D ultrasound. It has been shown that controlled ovarian hyperstimulation has a great impact on the uterine lining, which leads to different study results for the predictive value of endometrial factors measured on different cycle days. There is no clear consensus on whether endometrial factors are appropriate to predict treatment outcome and if so, which one is suited best. The aim of this review is to summarize recent findings of studies about the influence of endometrial thickness, volume and pattern on IVF- and ICSI-treatment outcome and provide an overview of future developments in the field.

  8. Safety of total laparoscopic modified radical hysterectomy with or without lymphadenectomy for endometrial cancer

    Directory of Open Access Journals (Sweden)

    Masakazu Kitagawa

    2017-02-01

    Conclusion: Total laparoscopic modified radical hysterectomy is safe and feasible for the treatment of early stage endometrial cancer. This procedure can be an alternative to total laparoscopic hysterectomy, especially when the uterus must be removed completely.

  9. Endometrial Carcinoma in a 26-Year-Old Patient with Bardet-Biedl Syndrome

    Directory of Open Access Journals (Sweden)

    Olga Grechukhina

    2018-01-01

    Full Text Available Background. Bardet-Biedl Syndrome (BBS is a rare genetic condition characterized by cognitive impairment, dysmorphism, central obesity, and diabetes mellitus, among other abnormalities. Although some of these characteristics are known independent risk factors for endometrial cancer and its precursors, the association between BBS and endometrial cancer is underreported. Case. We present the case of a 26-year-old patient with BBS and clinical signs of hyperestrogenism who presented with abnormal uterine bleeding and was diagnosed with endometrioid adenocarcinoma. She ultimately underwent definitive surgical treatment with hysterectomy and bilateral salpingectomy. Conclusions. This is one of only a few reports in the literature describing the association of BBS and endometrioid endometrial adenocarcinoma. Given the association of BBS with risk factors for hyperestrogenism such as truncal obesity, hyperinsulinemia, and ovulatory dysfunction, providers should have increased suspicion for endometrial cancer in young patients with BBS and abnormal uterine bleeding.

  10. Focal Endometrial Adenocarcinoma in Atypical Polypoid Adenomyoma of Low Malignant Potential

    Directory of Open Access Journals (Sweden)

    Coskun Salman

    2009-12-01

    This report describes a perimenopausal woman with atypical polypoid adenomyoma of low malignant potential with focal adenocarcinoma on endometrial biopsy who subsequently underwent hysterectomy in which no residual malignant lesion was found.

  11. Spontaneous pneumothorax after intensive chemotherapy in endometrial cancer: A rare complication

    Directory of Open Access Journals (Sweden)

    Jen-Ruei Chen

    2014-06-01

    Conclusion: Rapid shrinkage of a pulmonary space-occupying tumor sometimes causes rare but life-threatening spontaneous pneumothoraces. We report the first case of a spontaneous pneumothorax after using paclitaxel plus carboplatin in the treatment of endometrial cancer.

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

    Science.gov (United States)

    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

  13. Factors affecting the outcome of "endometrial scratch" in women with recurrent implantation failure.

    Science.gov (United States)

    Coughlan, Carol; Yuan, Xi; Demirol, Aygul; Ledger, William; Li, Tin Chiu

    2014-01-01

    To examine factors affecting the outcome of the endometrial scratch in women with recurrent implantation failure. A total of 57 eligible patients with a history of recurrent implantation failure underwent an endometrial biopsy in the luteal phase of the menstrual cycle in the month immediately preceding the embryo transfer cycle. The comparative group consisted of a retrospective cohort of 66 women with recurrent implantation failure but without endometrial biopsy. There were no significant differences between the intervention and control groups in terms of age, follicle-stimulating hormone (FSH), free androgen index, anti-Müllerian hormone, body mass index, the number of embryos transferred, and the number of embryo transfer cycles. The clinical pregnancy rate in the intervention group (53%) was significantly (p 10 IU/L. Women with a normal FSH are more likely to derive benefit from endometrial scratch.

  14. Outcome of ovarian preservation during surgical treatment for endometrial cancer: A Taiwanese Gynecologic Oncology Group study

    Directory of Open Access Journals (Sweden)

    Hei-Yu Lau

    2015-10-01

    Conclusion: Preservation of bilateral ovaries does not increase cancer-related mortality. A more conservative approach to surgical staging may be considered in premenopausal women with early-stage endometrial cancer without risk factors.

  15. Diagnostic delay, quality of life and patient satisfaction among women diagnosed with endometrial or ovarian cancer

    DEFF Research Database (Denmark)

    Robinson, Kirstine M; Christensen, Karl Bang; Ottesen, Bent

    2012-01-01

    This study investigates the association between diagnostic delay (total delay), quality of life (QoL) and patient satisfaction, and the associations between QoL and patient satisfaction scores and survival for women diagnosed with ovarian or endometrial cancer....

  16. The accuracy of magnetic resonance imaging for preoperative deep myometrium assessment in endometrial cancer

    Directory of Open Access Journals (Sweden)

    Wan-Ju Wu

    2013-06-01

    Conclusion: In patients with endometrial cancer, a preoperative MRI contributes to accurate staging, allowing planning for the scale of surgery and preoperative counseling. In our study, the pretreatment identification of myometrium invasion provided the opportunity for small-scale surgery in the premenopausal women with early endometrial cancer. However, for the postmenopausal patients, the standard surgical procedure is indicated even if the degree of myometrium invasion is low.

  17. 17β-Hydroxysteroid Dehydrogenase Type 2 Expression Is Induced by Androgen Signaling in Endometrial Cancer

    Directory of Open Access Journals (Sweden)

    Chiaki Hashimoto

    2018-04-01

    Full Text Available Endometrial cancer is one of the most common female pelvic cancers and has been considered an androgen-related malignancy. Several studies have demonstrated the anti-cell proliferative effect of androgen on endometrial cancer cells; however, the mechanisms of the anti-cancer effect of androgen remain largely unclear. 17β-hydroxysteroid dehydrogenase type 2 (17β-HSD2, which catalyzes the conversion of E2 to E1, is known to be upregulated by androgen treatment in breast cancer cells. In this study, we therefore focused on the role of androgen on estrogen dependence in endometrial cancer. Dihydrotestosterone (DHT was found to induce 17β-HSD2 mRNA and protein expression in HEC-1B endometrial cancer cells. DHT could also inhibit cell proliferation of HEC-1B when induced by estradiol treatment. In 19 endometrioid endometrial adenocarcinoma (EEA tissues, intratumoral DHT concentration was measured by liquid chromatography/electrospray tandem mass spectrometry and was found to be significantly correlated with 17β-HSD2 immunohistochemical status. We further examined the correlations between 17β-HSD2 immunoreactivity and clinicopathological parameters in 53 EEA tissues. 17β-HSD2 status was inversely associated with the histological grade, clinical stage, and cell proliferation marker Ki-67, and positively correlated with progesterone receptor expression. 17β-HSD2 status tended to be positively associated with androgen receptor status. In 53 EEA cases, the 17β-HSD2-positive group tended to have better prognosis than that for the negative group with respect to progression-free survival and endometrial cancer-specific survival. These findings suggest that androgen suppresses the estrogen dependence of endometrial cancer through the induction of 17β-HSD2 in endometrial cancer.

  18. MR findings of ruptured endometrial cyst: Comparison with tubo-ovarian abscess

    International Nuclear Information System (INIS)

    Suzuki, Shigeru; Yasumoto, Mayumi; Matsumoto, Reiko; Andoh, Akihiko

    2012-01-01

    Objective: To evaluate the MR findings of ruptured endometrial cyst, focusing on the differentiation from tubo-ovarian abscess (TOA). Patients and methods: We reviewed the records of 21 patients who underwent preoperative MR examinations for TOAs (n = 15) or ruptured endometrial cysts (n = 6). We evaluated the presence of hyper-intense ascites and hyper-intense peritoneum in T1-weighted sequences, strong enhancement of the peritoneum, hyper-intense content and hyper-intense rim of the ovarian lesion in T1-weighted sequences, and strong wall enhancement of the ovarian lesion. χ 2 test was used to assess the relationship between TOA cases versus cases with ruptured endometrial cysts, and the three MR peritoneal findings. We evaluated the relationship between TOA versus non-infected endometrial cysts, and the ovarian MR peritoneal findings, too. Results: Hyper-intense ascites was found in all of the patients with ruptured endometrial cyst and none with TOA (p < 0.0001). Hyper-intense peritoneum was observed in only TOAs cases (4 of 8). Strong peritoneal enhancement was seen in 3 of the 3 patients with ruptured endometrial cyst and 7 of the 13 patients with TOA (p = 0.1366). Hyper-intense content of the ovarian lesion was seen more often in the non-infected endometrial cysts than in the TOAs (p = 0.001607), while hyper-intense rim was more frequent in TOAs (p = 0.000402). Strong wall enhancement was observed only in TOAs (11 of 15) (p = 0.001355). Conclusions: MR images are useful to differentiate ruptured endometrial cyst from TOA.

  19. The Presence of Endometrial Cells in Peritoneal Fluid of Women With and Without Endometriosis.

    Science.gov (United States)

    O, Dorien F; Roskams, Tania; Van den Eynde, Kathleen; Vanhie, Arne; Peterse, Daniëlle P; Meuleman, Christel; Tomassetti, Carla; Peeraer, Karen; D'Hooghe, Thomas M; Fassbender, Amelie

    2017-02-01

    To reinforce Sampson's theory of retrograde menstruation in the pathogenesis of endometriosis, proof should be provided that during menstruation endometrial cells are present in peritoneal fluid (PF). We hypothesize that the prevalence of PF samples containing endometrial cells is higher in patients with endometriosis than in controls without endometriosis during menstruation. We selected from our biobank PF samples of 17 reproductive-age women with (n = 9) or without (n = 8) endometriosis who had received a diagnostic laparoscopy for investigation of pain/infertility. Peritoneal fluid had been collected during laparoscopy in the menstrual phase of the cycle, centrifuged, and the resulting pellet was stored at -80°C. About 5-μm sections of frozen PF pellets were stained using the Dako Envision Flex system with primary antibodies against epithelial cell adhesion molecule (Ep-CAM; endometrial epithelial cells), CD10 (endometrial stromal cells), prekeratin (epithelial/mesothelial cells), vimentin (endometrial/mesothelial/immune cells), calretinin (mesothelial cells), and CD68 (macrophages). The PF cells positive for Ep-CAM were detected in 5 of 9 patients with endometriosis and 6 of 8 controls ( P = .62). CD10 stained positively in 6 of the 9 patients with endometriosis and 3 of the 8 controls ( P = .35). Calretinin and prekeratin staining showed the presence of mesothelial cells in all pellets. Vimentin stained approximately 100% of the PF cells. CD68+ macrophages represented >50% of cells in all pellets. The prevalence of PF samples containing endometrial epithelial and stromal cells was not higher in patients with endometriosis than in controls without endometriosis during menstruation. Our findings question the relevance of endometrial cells in PF for the pathogenesis of endometriosis and support the importance of other mechanisms such as immune dysfunction and/or endometrial stem cells.

  20. Benign endometrial proliferations mimicking malignancies: a review of problematic entities in small biopsy specimens.

    Science.gov (United States)

    Ip, Philip Pun-Ching

    2018-02-14

    Benign proliferations that mimic malignancies are commonly encountered during the course of assessment of small and fragmented endometrial samples. Although benign, endometrial epithelial metaplasias often coexist with premalignant or malignant lesions causing diagnostic confusion. The difficulty with mucinous metaplasia lies in its distinction from atypical mucinous glandular proliferations and mucinous carcinomas, which are associated with significant interobserver variability. Papillary proliferation of the endometrium is commonly associated with hormonal drugs and endometrial polyps and is characterised by papillae with fibrovascular cores covered by epithelial cells without cytologic atypia. They are classified into simple or complex papillary proliferations depending on the architectural complexity and extent of proliferation. Complex papillary proliferations are associated with a high risk of concurrent or subsequent hyperplasia with atypia/carcinoma. Papillary proliferations may have coexisting epithelial metaplasias and, most commonly, mucinous metaplasia and syncytial papillary change. Those with striking mucinous metaplasia overlap morphologically with papillary mucinous metaplasia. The latter has been proposed as a precursor of endometrial mucinous carcinoma. Misinterpreting the Arias-Stella reaction as a malignant or premalignant lesion is more likely to occur if the pathologist is unaware that the patient is pregnant or on hormonal drugs. Endometrial hyperplasia with secretory changes may occasionally be difficult to distinguish from the torturous and crowded glands of a late secretory endometrium. Endometrial